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  • Electronic Resource  (875)
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  • 2005-2009
  • 1990-1994  (875)
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  • 1950-1954
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  • 1
    Electronic Resource
    Electronic Resource
    Verapamil induces increased bone volume and osteopenia in female rats but has the opposite effect in male rats (1992)
    Springer
    Calcified tissue international 50 (1992), S. 524-526 
    Details
    ISSN: 1432-0827
    Keywords: Verapamil ; Bone ; Osteopenia ; Rat ; Female ; Intestinal calcium absorption
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary Verapamil inhibits the intestinal absorption of calcium (Ca) and increases serum parathyroid hormone in rats. The effects of verapamil on bone tissue after long-term treatment is, however, not well described. Adult female and male Sprague-Dawley rats received verapamil in their drinking water at a dosage of 0.075 mg/ml (low dose) or 0.75 mg/ml (high dose) for 12 weeks; control rats received only drinking water. All rats were fed a diet containing 0.1% Ca and 0.5% P. In female rats, the amount of bone ash per volume was significantly reduced from 0.742 g/ml in controls to 0.713 g/ml after low-dose treatment of verapamil, and to 0.667 g/ml following high-dose treatment (P〈0.01). The tibial length was increased from 39.7 mm in controls to 40.3 mm or to 40.7 mm after low or high doses (P〈0.01). The tibial volume increased from 0.385 ml in controls to 0.397 ml after low doses and to 0.429 ml after high doses (P〈0.01). In contrast, in male rats the amount of bone ash per volume was significantly increased from 0.578 g/ml in controls to 0.580 g/ml after low doses and to 0.620 g/ml after high doses of verapamil (P〈0.01). The tibial bone volume in males as decreased from 0.633 ml in controls to 0.641 ml after low doses and to 0.583 ml after high doses (P〈0.05). The tibial length in the males was not changed by verapamil. The intestinal absorption of Ca was reduced in male rats from 5.28 in controls to 4.03 (serosa/mucosa) after low-dose treatment and to 2.46 after high-dose treatment with verapamil (P〈0.05). In female rats, the intestinal absorption of Ca did not change after verapamil treatment. Thus, chronic treatment with verapamil in female rats induced osteopenia whereas in male rats bone growth was inhibited.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00582167
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  • 2
    Electronic Resource
    Electronic Resource
    Acidic phosphoproteins from bone matrix: A structural rationalization of their role in biomineralization (1992)
    Springer
    Calcified tissue international 50 (1992), S. 391-396 
    Details
    ISSN: 1432-0827
    Keywords: Bone ; Matrix ; Phosphoproteins ; Biomineralization ; Calcium ; Nucleation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary Osteopontin, bone sialoprotein, and bone acidic glycoprotein-75 are three acidic phosphoproteins that are isolated from the mineralized phase of bone matrix, are synthesized by osteoblastic cells, and are generally restricted in their distribution to calcified tissues. Although each is a distinct gene product, these proteins share aspartic/glutamic acid contents of 30–36% and each contains multiple phosphoryl and sialyl groups. These properties, plus a strict relationship of acidic macromolecules with cell-controlled mineralization throughout nature, suggest functions in calcium binding and nucleation of calcium hydroxyapatite crystal formation. However, direct proof for such roles is still largely indirect in nature. The purpose of this review is to present two speculative hypotheses regarding acidic phosphoprotein function. The goal was to use new sequence information along with database comparisons to develop a structural rationalization of how these proteins may function in calcium handling by bone. For example, our analysis has identified a conserved polyacidic stretch in all three phosphoproteins which we propose mediates metal binding. Also, conserved motifs were identified that are analogous with those for casein kinase II phosphorylation sites and whose number correlates well with that of phosphoryl groups/protein. A two-state conformational model of calcium binding by bone matrix acidic phosphoproteins is described which incorporates these findings.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00296767
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  • 3
    Electronic Resource
    Electronic Resource
    Determination of histamine and polyamines in calcified tissues of mice: Contribution of mast cells and histidine decarboxylase to the amount of histamine in the bone (1992)
    Springer
    Calcified tissue international 51 (1992), S. 67-71 
    Details
    ISSN: 1432-0827
    Keywords: Histamine ; Polyamines ; Mast cells ; Histidine decarboxylase ; Bone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary A simple method for determining histamine and polyamines in various tissues was devised. The method, however, could not be applied to calcified tissues, because the high concentration of Ca2+ in the extract interferes with the chromatographic separation of these amines. By treating the extracts from calcified tissues with K2CO3, we succeeded in removing the Ca2+, and the method could then be applied to determine the amines in bone tissues of mice. By using this method, we examined the contribution of mast cells and histidine decarboxylae (HDC) to the amount of histamine in the bone. The results indicate that (1) the HDC activity in the bone is the highest among the tissues of normal mice, and the histamine produced by the HDC in the bone is metabolized rapidly; (2) a major part of HDC in the bone is present in the bone marrow cells other than mast cells, and most of histamine in the bone is attributable to the histamine pooled in mast cells; (3) mast cells in the diaphysis are located largely along the endosteal lining; and (4) the method devised in this study may be useful for studying the roles of histamine (or mast cells) and polyamines in calcified tissues.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00296220
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  • 4
    Electronic Resource
    Electronic Resource
    Postnatal development of central auditory frequency maps (1992)
    Springer
    Journal of comparative physiology 170 (1992), S. 129-143 
    Details
    ISSN: 1432-1351
    Keywords: Ontogeny ; Auditory system ; Tonotopy ; Chicken ; Rodent ; Cat ; Bat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary In the early postnatal period of many mammals and in the perihatching period of chicks the auditory ranges are restricted to the species-specific low- and mid-frequency ranges. During subsequent development, the high frequency hearing expands (depending on the species) by 1–4 octaves. Adult-like audition is established between the 4th and the 7th week. It is still discussed controversially, how the extension of the auditory ranges relates to the maturation of orderly frequency representation in the cochleae of the respective species. The present review summarizes investigations of the development of tonotopy in nuclei of the central auditory system, and discusses how the centrally acquired data might contribute to the understanding of the maturation of cochlear stimulus transduction and to the development of frequency maps.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00196895
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  • 5
    Electronic Resource
    Electronic Resource
    Earlier wrist fracture: A confounding factor in distal forearm bone screening (1992)
    Springer
    Osteoporosis international 2 (1992), S. 201-204 
    Details
    ISSN: 1433-2965
    Keywords: Bone ; Distal radius ; Fracture ; Single photon absorptiometry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Thirty-six women aged 60, 70 or 80 years who had fractured one of their distal radii (Colles' fracture) 0 to 35 (median 10) years earlier were examined in this population-based study. Single photon measurements (SPA) were performed on both arms 1 cm and 6 cm proximal to the styloid process of the ulna. All women were questioned about earlier wrist fractures and which, if any, side had been affected. Information about the type and site of the fracture was also gathered from the hospital records. The bone mineral content (BMC) was found to be increased by almost 20% in the once-fractured radius at the distal measuring site (1 cm) when compared with the unaffected side. This difference did not seem to diminish with time. At the proximal measuring site there was no difference between the once-fractured and the non-fractured side. There was a progressive loss of bone mineral in the once-fractured arm during the first years after the fracture however. This appeared to be reversed after about 10 years to a relative gain, even though the correlation was weak. Six of the 36 women could not remember which side had been fractured and five could not remember having had such a fracture at all. Determination of osteoporosis by measuring forearm BMC with single photon densitometry is therefore of limited value in some women of the oldest age groups.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01623927
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  • 6
    Electronic Resource
    Electronic Resource
    Amegakaryocytic thrombocytopenia and immune-mediated haemolytic anaemia in a cat (1992)
    Springer
    Comparative clinical pathology 2 (1992), S. 175-178 
    Details
    ISSN: 1433-2981
    Keywords: Amegakaryocytic thrombocytopenia ; Cat ; Haemolytic anaemia ; Immune-mediated diseases
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract An eleven-month-old female spayed domestic shorthair cat was presented for investigation of pruritic skin lesions and haemorrhage. Haematological evaluation revealed a markedly regenerative anaemia, neutrophilia with left shift, monocytosis, basophilia and severe thrombocytopenia. The direct antiglobulin test and serum antinuclear antibody tests were positive. Serologic and immunofluorescent antibody tests for feline leukaemia virus were negative. Bone marrow cytology revealed a lack of megakaryocytes with erythroid and myeloid hyperplasia. A peritoneopericardial diaphragmatic hernia was detected ultrasonographically, but was not considered to be related to the haematologic abnormalities. An immune-mediated aetiology for the amegakaryocytic thrombocytopenia was considered likely based on the concomitant positive direct antiglobulin and antinuclear antibody tests, but the cat responded poorly to short-term immunosuppressive therapy and was euthanized.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00426174
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  • 7
    Electronic Resource
    Electronic Resource
    Epithelioid hemangioendothelioma of bone A report of two cases and review of the literature (1992)
    Springer
    Skeletal radiology 21 (1992), S. 509-513 
    Details
    ISSN: 1432-2161
    Keywords: Epithelioid hemangioendothelioma ; Bone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Epithelioid hemangioendothelioma is the prototype of a group of vascular tumors characterized by epithelioid or histiocytoid endothelial cells. Epithelioid hemangioendothelioma of bone is a rare lesion that constitutes fewer than 1% of primary malignant skeletal neoplasms. We describe two cases that illustrate the spectrum of radiographic features seen with this neoplasm, and also present its appearance on magnetic resonance imaging.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00195232
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  • 8
    Electronic Resource
    Electronic Resource
    Morphology of a dicephalic cat (1992)
    Springer
    Anatomy and embryology 185 (1992), S. 45-55 
    Details
    ISSN: 1432-0568
    Keywords: Dicephalia ; Anterior duplications ; Congenital malformations ; Conjoined twins ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A detailed anatomical study of a dicephalic iniodymic monosomic cat in conjunction with the morphogenetical implications of the observed anomalies is presented. The animal exhibited two heads joined at the level of an anomalous medial exoccipital bone. Two brains and two foramina magna were present. The vertebral column was single but the cranial cervical vertebrae (C2 to C5) had doubled bodies. Cervical rachischisis with myeloschisis were associated defects. Two nasopharyngeal and oropharyngeal cavities converged caudally into a single laryngopharynx. The esophagus, larynx and trachea were single. Duplication of the tongue and hyoid apparatus was present. Palatoschisis affected both oral cavities. Hypoplasia of the anatomical structures in the medial aspects of both heads was observed. Microphthalmia was also observed in both medial eyes. Comparative aspects of the morphology, causative agents, and mechanisms and anomalous morphogenesis of anterior duplications are reviewed and discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00213600
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  • 9
    Electronic Resource
    Electronic Resource
    Repetitive loading, in vivo, of the tibia and femora of rats: Effects of a single bout of treadmill running (1992)
    Springer
    Calcified tissue international 50 (1992), S. 193-196 
    Details
    ISSN: 1432-0827
    Keywords: Bone ; Mechanical properties ; Fatigue microdamage ; Exercise
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary The presence of microdamage in the tibiae and femora of rats following repetitive loading in vivo was investigated by subjecting 48 male rats, aged 12 weeks, to treadmill running (26.8 m.min-1 on 10% grade) for 0.56 hours (5,000 cycles, E1), 1.13 hours, (10,000 cycles, E2), 2.27 hours (20,000 cycles, E3), and 3.4 hours (30,000 cycles, E4) with Group C as control. Following exercise, tibiae and femora were excised and the right limbs were tested in torsion at 180°.sec-1. Transverse sections were cut from the proximal, mid- and distal diaphysis of left tibiae and femora, bulk stained in basic fuchsin, cut to 50 μm thick, and examined for the presence of microdamage. Following these periods of loading, tibiae and femora showed no evidence of microdamage initiation, as evidenced by light microscopy, or corresponding alterations in mechanical properties. It was concluded that the magnitude of loading produced by single bouts of intensive exercise, which encompassed up to 30,000 loading cycles, was insufficient to initiate fatigue microdamage in tibiae or femora of rats.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00298800
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  • 10
    Electronic Resource
    Electronic Resource
    Competitive adsorption of magnesium and calcium ions onto synthetic and biological apatites (1992)
    Springer
    Calcified tissue international 51 (1992), S. 143-150 
    Details
    ISSN: 1432-0827
    Keywords: Adsorption ; Magnesium ; Calcium ; Apatite crystals ; Enamel ; Dentin ; Bone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary Magnesium (Mg) is a conspicuous constituent of hard tissues but its possible role in biomineralization is poorly understood. It is possible that Mg2+ adsorbed onto bioapatites may contribute to the modulation of crystal growth as such inhibitory activity has been reported for synthetic apatites. The present study was undertaken to determine the adsorption isotherms of Mg ions onto synthetic apatites and biominerals in tooth and bone tissues in the presence of other ions of natural occurrence. Synthetic crystals used as adsorbents were hydroxyapatite and, as a better prototype for the biomineral, Mg-containing carbonatoapatite. Human enamel and dentin materials were obtained from extracted, caries-free, permanent teeth. Porcine dentin materials at two developmental stages were obtained from erupted deciduous and unerupted permanent teeth of a 6-month-old slaughtered piglet. Porcine bone was obtained from the cortical portion of the mandible of the same animal. All biomineral samples were pulverized and then treated by plasma ashing (deproteination) at about 60°C. Each of the powdered samples was equilibrated in solutions containing various initial concentrations of Mg2+, Ca2+, and Na+ (or K+) as nitrate salts. Following equilibration, concentrations (and activities) of magnesium and calcium ions in the experimental solution were determined. The pH values of the equilibrium solutions were in the range of 6.2–6.5. Experimental data of the Mg adsorption onto hydroxyapatite were interpreted on the basis of a Langmuir-type model for binary systems assuming competition of Mg2+ and Ca2+ for the same adsorption sites on the crystal surfaces of the apatites. According to this model, the adsorbed Mg is expressed as a function of the ionic activity ratio (Mg2+)/(Ca2+) in the equilibrium solution. The model contains two parameters, the adsorption selectivity constant Ks and the maximum number of adsorption sites N (μmol/g). The numerical values of Ks were similar for all adsorbents used (synthetic and biological) and indicated the preferential adsorption of Ca2+ probably due to spacial restrictions extending to the very surface of the crystals. The initial level of Mg2+ in the surface pool was different in the various biominerals, probably reflecting the composition of fluid in which the biominerals were formed. Whereas the surface pool of Mg of human enamel was marginal, only 5% of the total Mg, significant fractions of the total Mg in human and porcine dentins (about 20–30%), and porcine bone (about 40%) existed on the crystal surfaces. There were significant differences in the total Mg and the value of the parameter N between young (unerupted) and mature (erupted) dentin minerals. It was ascertained that the occupancy of adsorption sites by Mg ions became greater with maturation of the dentin tissues. The overall results suggest that the Mg-mineral interaction in tooth and bone tissues may be a highly tissue-specific process, presumably reflecting differences in fluid composition (particularly Ca and Mg activities) responsible for biomineralization.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00298503
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  • 11
    Electronic Resource
    Electronic Resource
    An FT-IR microscopic investigation of the effects of tissue preservation on bone (1992)
    Springer
    Calcified tissue international 51 (1992), S. 72-77 
    Details
    ISSN: 1432-0827
    Keywords: Fixation ; FT-IR microscopy ; Infrared spectroscopy ; Bone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary Fourier transform infrared microscopy is a powerful tool for the characterization of mineral and protein in histologic sections of bone. This study was concerned with determining whether techniques used to preserve these tissties and to prepare them for sectioning had an effect on spectral properties. The υ1, υ3 phosphate bands in the 900–1200 cm-1 spectral region were used to evaluate the structure of the apatitic mineral in fresh-frozen, ethanol-fixed, and formalin-fixed 35-day-old rat femurs; fresh-frozen and formalin-fixed 20-day-old fetal rat femurs; ground 35-day-old rat diaphyseal bone samples; and formalin-fixed, methacrylate-embedded ground diaphyseal bone. The crystallinity (crystal size and perfection) of the bone apatite was assessed by a curve-fitting analysis of the υ1, υ3 phosphate bands. Results indicate that ethanol or formalin fixation of the 35-day-old intact rat femur, and formalin fixation and embedding of the ground rat bone do not significantly alter the crystallinity of the apatite. However, formalin fixation of the fetal rat bone did alter the structure of the apatite mineral phase. In addition, evaluation of protein secondary structure in the 35-day-old rat femur from the Amide I and Amide II vibrations near 1650 and 1550 cm-1, respectively, revealed that protein conformation was altered by ethanol fixation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00296221
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  • 12
    Electronic Resource
    Electronic Resource
    Minimal levels of serum estradiol prevent postmenopausal bone loss (1992)
    Springer
    Calcified tissue international 51 (1992), S. 340-343 
    Details
    ISSN: 1432-0827
    Keywords: Menopause ; Estrogens ; Bone ; Osteoporosis ; Calcium
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary Biochemical parameters reflecting bone resorption [urinary calcium/creatinine (Ca/Cr) and hydroxyproline/ creatinine (OH/Cr)] were related to serum estrogens [estrone (E1) and estradiol (E2)] in 262 healthy women including 158 patients receiving estrogen replacement therapy (ERT) for at least 6 months, 49 eugonadal women, and 55 untreated postmenopausal women. A significant (P〈0.001) correlation exists between serum E2 and Ca/Cr: Ca/Cr (mg/dl)=-0.00044 E2 (pg/ml)+0.129 (n=262; r=-0.37), serum E2 and OH/Cr: (OH/Cr (mg/g)=-0.049 E2 (pg/ml)+18.76 (n=262; r=-0.36), serum E1 and Ca/Cr: Ca/Cr (mg/dl)=-0.0003 E1 (pg/ml)+0.127 (n=261; r=-0.28) but not between serum E1 and OH/Cr. Women with circulating levels of E2 between 60 and 90 pg/ml have a significant (P〈 0.01) reduction of Ca/Cr and OH/Cr when compared with those with lower levels of E2. Higher values of E2 do not provide additional benefit. We conclude that in postmenopausal women receiving an estrogen replacement therapy (ERT), a significant reduction of bone resorption is achieved when circulating levels of estradiol reach a value (60 pg/ml) corresponding to the one measured, in eugonadal women, during the last days of the early follicular phase of the menstrual cycle. We suggest that oral or percutaneous ERT should induce a minimal value of 60 pg/ml to prevent postmenopausal bone loss.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00316876
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  • 13
    Electronic Resource
    Electronic Resource
    Effects of cyclosporin A on rat osteoblasts (ROS 17/2.8 cells) in vitro (1992)
    Springer
    Calcified tissue international 51 (1992), S. 291-297 
    Details
    ISSN: 1432-0827
    Keywords: Bone ; Osteoblast ; Cyclosporin A ; Attachment ; Proliferation ; Alkaline phosphatase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary The effects of the immunosuppressive drug cyclosporin A (CsA) were evaluated on ROS 17/2.8 cells in vitro. ROS cells were treated with CsA (0, 0.5, 1.0, 5.0 μg/ml) for 3 days with and without bovine parathyroid hormone (bPTH) (1–34) 10 nM. CsA at 0.5, 1.0, 5.0 μg/ml without PTH and at 5.0 μg/ml in the presence of PTH significantly inhibited proliferation, as determined by a tetrazolium colorimetric assay. In addition, ROS cell number was significantly reduced at 3 and 4 days with CsA (5.0 μg/ml) without affecting cell viability. Incorporation of [3H]-thymidine into DNA was significantly reduced by 3.0 and 5.0 μg/ml CsA after 12 and 24 hours exposure. Basal and 1,25-dihydroxyvitamin D3-stimulated alkaline phosphatase levels in confluent ROS cells were reduced (P〈0.05) with CsA (1.0 and 3.0 μg/ml). Pretreatment of ROS 17/2.8 cells with CsA did not alter PTH-stimulated cAMP levels or [125I]-PTHrP binding to ROS cells. CsA treatment of ROS 17/2.8 cells induced a spindle-shaped appearance with loss of attachment in confluent cultures. When ROS cells were cultured in CsA-containing media, cellular attachment at 6 and 12 hours was reduced (P〈0.05) compared with untreated ROS cells. These findings indicate that CsA was capable of inhibiting proliferation, cell number, mitogenesis, alkaline phosphatase levels, and cell attachment of ROS cells without affecting PTH binding or cAMP levels. This direct effect of CsA on osteoblasts may be important in changes of bone remodeling observed in CsA-treated humans and animals.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00334490
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  • 14
    Electronic Resource
    Electronic Resource
    Reproducibility of lateral spine scans using dual energy X-ray absorptiometry (1992)
    Springer
    Calcified tissue international 51 (1992), S. 255-258 
    Details
    ISSN: 1432-0827
    Keywords: Bone ; Densitometry ; Dual energy X-ray absorptiometry ; Lateral spine scanning ; Reproducibility
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary Reproducibility of lateral spine dual energy X-ray absorptiometry (LAT DEXA) scans using a Lunar DPX-L scanner was assessed in a cadaveric phantom and in patients. One hundred phantom measurements over 7 months demonstrated a longitudinal stability of 1.7% (coefficient of variation, CV). Additional scans were performed with the phantom rotated by up to 20° in each of the three orthogonal planes to assess the effects of variable patient positioning. Horizontal and vertical rotation of the spine had little effect on the estimated bone mineral density (BMD), however, axial rotation of greater than 8° led to errors in the BMD measurement. One hundred consecutive patients had two lateral scans performed within 1 month. BMD (range 0.10–1.6 g/cm2) was determined for each scan by one operator. Significant overlap from ribs and pelvis was often seen with L2 and L4 vertebrae but one vertebra (L3) could be measured in every case. Intraoperator and interoperator variability was assessed by three experienced operators, each analyzing 10 patients' scans on five separate occasions, and was found to be less than 1.1% for a single vertebra. BMD estimation of vertebral bodies and midslices by lateral DEXA scans (CV% of 3.8% and 4.6%) have a 95% confidence interval of 0.074 g/cm2 and 0.096 g/cm2, respectively for two vertebrae. This variability is due mainly to axial rotation, with operator variability, horizontal rotation, and vertical rotation having little effect on BMD estimation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00334484
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  • 15
    Electronic Resource
    Electronic Resource
    Synthetic parathyroid hormone-like protein (1–74) is anabolic for bone in vivo (1992)
    Springer
    Calcified tissue international 51 (1992), S. 30-34 
    Details
    ISSN: 1432-0827
    Keywords: PTHRP ; Anabolic ; Rat ; Bone ; Potency
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary Parathyroid hormone-related protein (PTHRP) has recently been purified from human tumors associated with the syndrome of humoral hypercalcemia of malignancy. The gene encoding PTHRP has been cloned, and based on predicted amino acid sequence, polypeptides comprising the first 36 [36Tyr(1–36) PTHRP amide] and 74 [(1–74)PTHRP] amino acids have been synthesized. Human (h) PTHRP (1–36) and (1–74) are potent bone-resorbing agents, and are catabolic for bone in vivo when given continuously at high doses. Bovine parathyroid hormone (bPTH) (1–34) is also catabolic for bone at high dose levels, but when given in low doses for weeks to months, it is anabolic. Although PTHRP possess several PTH-like properties in bone, hPTHRP (1–34) is reported to be only weakly anabolic in vivo. As polypeptide length influences PTHRP action, we evaluated hPTHRP(1–74) as an anabolic agent for bone in vivo. Twenty-four 4-week-old male Sprague-Dawley rats were given daily subcutaneous injections of hPTHRP(1–74) (1 and 2 nmol/100 g body weight, bw), bPTH(1–34) (4 nmol/100 g bw) or vehicle. Rats were sacrificed on day 12, and serum calcium, phosphorus, and 1,25 dihydroxyvitamin D and femoral bone dry weight, calcium content, and hydroxyproline content were measured. Serum calcium and phosphorus were equivalent in all groups. A significant increase in dry bone weight was observed in both PTHRP-treated groups compared with controls. PTHRP also caused a significant, dose-dependent increase in bone calcium and hydroxypro-line content. Results of these studies indicate that PTHRP (1–74) is anabolic for bone in vivo when administered at low-dosage levels for a prolonged period.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00296214
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  • 16
    Electronic Resource
    Electronic Resource
    Electromyographic studies of neck muscles in the intact cat (1992)
    Springer
    Experimental brain research 88 (1992), S. 59-66 
    Details
    ISSN: 1432-1106
    Keywords: Reflexes ; Electromyography ; Nuchal afferents ; Neck muscles ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Short-latency reflexes were studied in the neck muscles of four alert cats following electrical stimulation of nerves supplying biventer cervicis (BC), splenius (SP) or rectus capitis posterior (RCP). Reflexes were assessed by comparing levels of EMG activity of muscles before and after each stimulus, as the cats lapped milk, licked their paws or walked on a treadmill. When BC or SP nerves were stimulated at 1.5–4 times threshold (T) for their motor axons, no short-latency heteronymous reflexes could be identified in most neck muscles. However, stimulation of RCP nerves produced inhibitory effects as early as 3–4 ms in the ipsilateral BC, CM, and SP muscles and 6 ms in contralateral BC. At stimulus strengths above 4xT, a more complex pattern of inhibitory or excitatory effects was observed in CM, SP and the intervertebral muscle spinalis dorsi. The reflex effects were attenuated or abolished by partial or complete C1 dorsal rhizotomy (2 cats). Cervicocollic reflex data may need to be reevaluated to consider the possible effects of disinhibition rather than excitation in short-latency reflex pathways.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02259128
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  • 17
    Electronic Resource
    Electronic Resource
    Auditory cortex neurons sensitive to correlates of auditory motion: underlying mechanisms (1992)
    Springer
    Experimental brain research 88 (1992), S. 169-180 
    Details
    ISSN: 1432-1106
    Keywords: Auditory cortex ; Motion ; Depth ; Binaural interaction ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Neuronal response properties such as phasic vs. tonic, onset vs. offset, monotonicity vs. non-monotonicity, and E/E vs. E/I, can be shown to act synergistically suggesting underlying mechanisms for selectivity to binaural intensity correlates of auditory sound source motion. Both identical (diotic), and oppositely directed dichotic AM ramps were used as stimuli in the lightly anesthetized cat, simulating motion in four canonical directions in 3-dimensional space. Motion in either azimuthal direction evokes selective activity in cells which respond best to the onset of monaural sound in one ear and show a decreased response to binaural stimulation (E/I or I/E). In some cells specificity is increased by “off” components in the non-dominant ear. Although these cells fire only at the onset of stationary sound, they fire throughout oppositely directed AM ramps. Motion toward or away from the head evokes responses from EE cells; strong binaural facilitation increases selectivity for motion in depth. The sharpness of direction of tuning was related to the degree of binaural facilitation in E/E cells. Selectivity for sound moving away from the head is correlated with “off” responses, while “on” responses correlate with preference for motion toward the head. Most units showed a monotonic rate function as AM ramp excursion and rate was increased. One third were selective for slower rates of intensity change and may therefore encode slower rates of stimulus motion, as well as direction of movement. The findings suggest that neural processing of auditory motion involves neural mechanisms distinct from those involved in processing stationary sound location and that these mechanisms arise from interactions between the more traditionally studied response properties of auditory cortex neurons.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02259138
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  • 18
    Electronic Resource
    Electronic Resource
    Simultaneous recording of lagged and nonlagged cells in the cat dorsal lateral geniculate nucleus (1992)
    Springer
    Experimental brain research 88 (1992), S. 229-232 
    Details
    ISSN: 1432-1106
    Keywords: Dorsal lateral geniculate nucleus ; Lagged cells ; Nonlagged cells ; Sensory processing ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary It has been suggested that lagged and nonlagged cells in the cat dorsal lateral geniculate nucleus (LGN) represent state-dependent response modes of the same class of LGN cells. In two separate experiments with single-unit recording in the LGN of anaesthetized and paralysed adult cats, a lagged and a nonlagged X-cell were recorded simultaneously with the same microelectrode. For each pair of cells, the amplitude of the action potentials was sufficiently different to allow separate compilation of peri-stimulus-time-histograms. For all 4 cells, the visual response pattern to a stationary flashing light spot was typical of their respective cell class. These findings support the hypothesis that lagged and nonlagged cells are separate cell classes and indicate that the population of LGN cells do not appear as lagged during one state of modulatory input and as nonlagged during another.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02259147
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  • 19
    Electronic Resource
    Electronic Resource
    A novel member to the family of perineuronal antigens associated with subpopulatios of central neurons in the rat (1992)
    Springer
    Experimental brain research 88 (1992), S. 345-354 
    Details
    ISSN: 1432-1106
    Keywords: Neuronal subsets ; Pericellular antigen ; Monoclonal antibody ; Cat ; 301 ; VC1.1 ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We reported earlier that monoclonal antibodies (MAbs) 473 and 376 gave perineuronal staining of different subsets of central neurons, and that both immunoreactivities were labile to treatment with chondroitinase ABC. On the other hand, MAb 1B5, the immunoreactivity to which is uncovered by chondroitinase ABC, stained a neuronal subset that included neurons positive to MAbs 473 and 376 (Fujita et al. 1989). We now report a new antibody, MAb 374, that stained perimeter of neurons of a subset different from those stained by MAbs 473, 376 and 1B5. In the rat central nervous system MAb 374-positive cells were found in the neocortex, thalamic reticular nucleus, hippocampus, cerebellar cortex and nuclei, and in the brain stem. MAb 374-immunoreactive neuropil was found in the medial habenular, arcuate, dorsal endopiriform nuclei, and the two plexiform layers of the retina. The immunoreactivity was not affected by treatment with chondroitinase ABC. Immunoblot experiments using a rat brain homogenate revealed a specific band at a position corresponding to a molecular weight of 600 kD.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02259110
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  • 20
    Electronic Resource
    Electronic Resource
    Spread of synaptic activity along parallel fibres in cat cerebellar anterior lobe (1992)
    Springer
    Experimental brain research 88 (1992), S. 615-622 
    Details
    ISSN: 1432-1106
    Keywords: Cerebellar cortex ; Mossy fibre input ; Parallel fibres ; Field potentials ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 1. Mossy fibre evoked activity in the cerebellar cortex elicited by peripheral electrical stimulation was studied in chloralose anesthetized cats. The distribution of intracortical field potentials in the C3 and D zones was mapped in order to determine if there is a spread of synaptic activity outside the mossy fibre termination area. This area was identified by the presence of short latency synaptic field potentials in the granular layer. 2. Molecular layer field potentials were recorded up to 1.5 mm outside the mossy fibre termination area. The latencies of these potentials increased with increasing distance from the mossy fibre termination area, corresponding to a conduction velocity of about 0.4 m/s. 3. Recordings from Purkinje cells, within and outside the mossy fibre termination area, revealed an increase of simple spike activity at latencies corresponding to those of the field potentials in the same location. 4. From the spatial and temporal characteristics of the evoked activity, it is concluded that a mossy fibre input results in spread of synaptic activity along the parallel fibres. 5. The findings are discussed in relation to the recently discovered microzonal organization of the C3 zone. It is proposed that the organization of this zone offers a possibility for the control of muscle synergies, each synergy being represented by a mossy fibre input and the specific set of microzones activated by this input via the parallel fibres.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00228190
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  • 21
    Electronic Resource
    Electronic Resource
    Axonal trajectories of single Forel's field H neurones in the mesencephalon, pons and medulla oblongata in the cat (1992)
    Springer
    Experimental brain research 89 (1992), S. 484-495 
    Details
    ISSN: 1432-1106
    Keywords: Forel's field H ; Oculomotor nucleus ; Reticular formation ; Central tegmental tract ; Eye movements ; Neck movements ; Vertical ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We studied axonal trajectories of single Forel's field H (FFH) neurones (n= 19) in the mesencephalon, pons and medulla by systematic antidromic threshold mapping in cats and differentiated them into two major types. Type I neurones were characterized by projections to the oculomotor nucleus (IIIn) and type II neurones by lack of projections to the IIIn. 2. Type I neurones (11/19) were further classified into three subtypes by the lowest level of projections; type Ic (n = 3) which projected to the cervical cord and type Ib (n = 7) which terminated at the ponto-medullary level and type Ia (n = 1) at more rostral level. In the mesencephalon, stem axons passed just lateral to the IIIn and projected collaterals to the IIIn and the ventral part of the periaqueductal gray matter. In the lower brain stem, stem axons of type Ib and Ic neurones passed in the dorsal part of the reticular formation or in the medial longitudinal fasciculus and projected collaterals to the dorsal part of the nucleus reticularis pontis caudalis (NRPC) and the nucleus reticularis gigantocellularis (NRG) and the reticular formation underlying the nucleus prepositus hypoglossi (PH) and the raphe region. Projections to the superior colliculus were observed in two cases. 3. Type II neurones (8/19) were classified into 2 type IIb projecting to the ponto-medullary reticular formation and 6 type IIc projecting to the cervical spinal cord. In the mesencephalon, stem axons passed through a more lateral region than those of type I and projected collaterals to the mesencephalic reticular formation and the red nucleus. In the lower brain stem, the stem axons passed in the ventral part of the reticular formation corresponding to the central tegmental tract and projected collaterals to the ventral part of the NRPC and NRG. Projections to the interstitial nucleus of Cajal, the inferior olive and the reticular formation underlying the PH were also observed. 4. The dorsal and ventral location of, respectively, stem axons of type I and type II neurones in the lower brain stem was confirmed in a larger number of neurones in experiments with restricted mapping. 5. There was not much difference in location of cell bodies of type I (totally n = 50) and type II (n = 46) neurones. The proportion of spinal-projecting neurones were larger in type II (21/46, 46%) than in type I (7/50, 14%) neurones.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00229872
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  • 22
    Electronic Resource
    Electronic Resource
    Binocular processing in the cat's dorsal lateral geniculate nucleus III. Spatial frequency, orientation, and direction sensitivity of nondominant-eye influences (1992)
    Springer
    Experimental brain research 89 (1992), S. 588-598 
    Details
    ISSN: 1432-1106
    Keywords: Lateral geniculate nucleus ; Vision ; Binocular ; Cortico-geniculate ; Orientation ; Sensitivity ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The present experiments examined the extent to which binocular processing in the cat's dorsal lateral geniculate nucleus (LGN) depends upon the spatial frequency, orientation, and direction of movement of stimuli presented to the nondominant eye. In Experiment 1, we tested the effects of varying these stimulus parameters on the responses of LGN cells to nondominant-eye stimulation. Sixteen of 34 cells tested had statistically significant responses to the nondominant eye and, in agreement with a previous study (Guido et al. 1989), the responsive cells were spatial-frequency sensitive. However, there was little evidence for orientation or direction sensitivity in responses to the nondominant eye: changes in discharge with changes in stimulus orientation and direction were small and were statistically significant in only nine of the cells. In Experiment 2, we tested the effects of varying spatial frequency, orientation, and direction of movement of stimuli presented to the nondominant eye on its ability to influence responses to the dominant eye (i.e., on binocular interactions). The dominant eye was stimulated with the optimal spatial frequency for the cell being tested. For 22 of 45 cells tested, nondominant-eye stimulation had a statistically significant effect on the response to the dominant eye. Fourteen of these cells showed band-pass spatial-frequency sensitivity in the nondominant-eye influence, and eight showed low-pass spatial-frequency sensitivity. However, only 11 of the cells had statistically significant variations in their binocular interactions that depended on the orientation or direction of stimuli presented to the nondominant eye. Furthermore, even for those cells, the effect of varying orientation and direction was only about half as strong as the effect of varying spatial frequency. We conclude that binocular processing in the LGN, including responses to the nondominant eye and nondominant-eye influences on responses to the dominant eye, are affected significantly by the spatial frequency of the nondominant-eye stimulus and relatively little by stimulus orientation or direction of movement. The significance of these findings for understanding the functions of LGN binocular processing is discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00229884
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  • 23
    Electronic Resource
    Electronic Resource
    Task-related differences in distribution of electromyographic activity within peroneus longus muscle of spontaneously moving cats (1992)
    Springer
    Experimental brain research 89 (1992), S. 682-685 
    Details
    ISSN: 1432-1106
    Keywords: EMG ; Hindlimb ; Kinesiology ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In the hindlimb muscle peroneus longus (PerL) of cats, electromyographic activity (EMG) was recorded from anterior and posterior regions during voluntary motor behaviour. In spite of the fact that this muscle is composed of units that all exert their forces in the same direction, the intra-muscular EMG distribution differed in a marked and reproducible way between different types of motor behaviour. Anterior as well as posterior regions were both strongly active in relation to the swing-phase of stepping. In comparison to this stepping-activity, there was a marked predominance of posterior PerL activity during hindlimb standing (or take-off for a jump) and an equally pronounced predominance of anterior PerL activity when the cat was preparing to land from being lifted (or at the end of a jump). It is suggested that these task-associated differences in EMG distribution reflect topographical aspects of the intraspinal organization of motor tasks.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00229893
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  • 24
    Electronic Resource
    Electronic Resource
    Synaptic potentials produced in jaw-closer and jaw-opener motoneurons by palatal stimulation (1992)
    Springer
    Experimental brain research 90 (1992), S. 233-240 
    Details
    ISSN: 1432-1106
    Keywords: Postsynaptic potentials ; Trigeminal motoneurons ; Jaw movements ; Palatal stimulation ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Excitation and inhibition of temporal and digastric motoneurons (Temp. and Dig. Mns) during transient jaw closing, the so-called jaw-closing reflex, were studied in cats. Application of diffuse pressure stimulation to the posterior palatal surface produced the jaw-closing reflex and it was found that mechanosensory inputs from the posterior palatal mucosa produce depolarizing potentials on the Temp. Mns responsible for jaw closure during the jaw-closing reflex. We have demonstrated that in one-third of 27 explored Temp. Mns the initial bursts of spikes were elicited before the onset of jaw closure, suggesting that these cells contribute to initiate jaw closure during the jaw-closing reflex. The remaining cells probably contributed to maintain the occlusal phase. Furthermore, it was found that mechanosensory inputs from the posterior palatal mucosa produce a hyperpolarization-depolarization sequence in the Dig. Mns responsible for the jawclosing reflex. In addition, when pressure stimulation was applied to the anterior palatal mucosa, sustained jaw opening was elicited and an increase of firing frequency of Dig. Mns occurred 40 ms before the onset of jaw opening and continued for 80 ms.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00227234
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  • 25
    Electronic Resource
    Electronic Resource
    Patterns of projections from area 2 of the sensory cortex to area 3a and to the motor cortex in cats (1992)
    Springer
    Experimental brain research 91 (1992), S. 85-93 
    Details
    ISSN: 1432-1106
    Keywords: Sensorimotor ; Somatosensory cortex ; Connectivity ; Corticocortical ; Fluorescent tracer ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Peripheral information reaches the motor cortex partly through corticocortical pathways that arise from two functional subdivisions, area 2 and area 3a, of the sensory cortex. These sensory areas are synaptically linked with one another. The patterns of connectivity and the different submodality input that each area receives suggest that they send different efferent signals to the motor cortex. The projections from area 2 to area 3a and to the motor cortex were studied with retrogradely transported fluorescent tracers. The pattern and distribution of neuronal labeling in area 2 was determined following injections of different tracers into the forelimb regions of area 3a and the motor cortex. The results showed that the projections from area 2 to the two target regions were topographically and somatotopically related. Multiple clusters of motor cortex projection neurons were found in area 2, and these clusters overlapped extensively with clusters of area 3a projection neurons. Although cells labeled with one of the dyes were often in close proximity to cells labeled with the other dye, no double-labeled cells were found. Two different laminar patterns were seen for the two populations of neurons. The projection to area 3a originated from cells located in layers II–III and layers V–VI. The projection to the motor cortex originated from cells spread throughout layers II–IV, but predominately in layer III. Differences in laminar arrangement of the two populations of cells suggest a directional flow of information processing in the sensorimotor cortex. While sensory feedback is essential for the execution of skilled motor tasks, the flow of information processing and connectivity in the cortex is not well understood. The data presented here offer insight into some aspects of the mechanisms of sensorimotor integration.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00230016
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  • 26
    Electronic Resource
    Electronic Resource
    A comparison of monaural and binaural responses to frequency modulated (FM) sweeps in cat primary auditory cortex (1992)
    Springer
    Experimental brain research 91 (1992), S. 435-454 
    Details
    ISSN: 1432-1106
    Keywords: Frequency modulated sweep ; Binaural response ; Primary auditory cortex ; Direction selectivity ; Speed selectivity ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Monaural and binaural single unit responses to frequency-modulated (FM) sweeps were compared in cat primary auditory cortex (AI). Both upward-directed (changing from low to high frequency) and downward-directed (changing from high to low frequency) FM sweeps were presented monaurally and binaurally at five rates of frequency modulation (referred to here as the speed of FM sweep). Two types of binaural FM sweep conditions were presented: (1) like-directed FM sweeps, in which identical FM sweeps were presented to both ears, and (2) opposite-directed FM sweeps, in which one ear was presented with one direction of FM sweep while the other ear was simultaneously presented with the opposite direction of FM sweep. In a sample of 78 cells, 33 cells were classified as EE (binaural facilitatory) and 45 were classified as EI (binaural inhibitory). Ninety-four percent of all units were sensitive to the direction and/or speed of FM sweeps. In general, under binaural stimulus conditions, EE cells responded optimally to like-directed FM sweeps, while EI cells preferred opposite-directed FM sweeps. When tested monaurally, 59% of all cells (both EE and EI) were direction selective, with the majority (76%) preferring downward-directed FM sweeps. When tested binaurally, most direction selective EE cells (60%) preferred upward-directed FM sweeps, while the majority of direction selective EI cells (71%) preferred downward-directed FM sweeps. Our analysis also allowed us to classify inhibitory responses of EI cells as either direction selective (37%) or non-direction selective (63%). For FM speed selectivity under monaural conditions, most EE cells preferred fast FM sweep rates (0.4–0.8 kHz/ms), while approximately equal numbers of EI cells preferred either slow (i.e., 0.05–0.1 kHz/ms) or fast (i.e., 0.4–0.8 kHz/ms) speeds. Under binaural conditions, the majority of EE and EI cells responded best to high speeds when tested with like-directed FM sweeps, while the preferred speed with opposite-directed FM sweeps was more broadly tuned. The results suggest the presence of binaural neural mechanisms underlying cortical FM sweep direction and speed selectivity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00227840
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  • 27
    Electronic Resource
    Electronic Resource
    Longterm impairment of cat optokinetic nystagmus following visual cortical lesions (1992)
    Springer
    Experimental brain research 88 (1992), S. 594-608 
    Details
    ISSN: 1432-1106
    Keywords: Optokinetic reflex ; Vestibulo-ocular reflex ; Cortical lesion ; Areas 17, 18, 19 ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Binocular and monocular gain of optokinetic nystagmus (OKN), OKN dynamics, vestibulo-ocular reflex (VOR) and VOR adaptation were measured in 5 normal cats and in 5 cats which underwent bilateral visual cortical lesions involving the 17–18 complex at least 4 months before testing. We observed longterm deficits after bilateral lesions involving area 17 and variable parts of area 18 but failed to observe deficits after 18–19 lesions. These deficits were limited to the OKN gain and the build-up time constant of OKN; the VOR and the optokinetic after-nystagmus (OKAN) time constant were within normal limits. Our results suggest that areas 17–18 operate in parallel to control the encoding of retinal slip velocity at the level of the nucleus of the optic tract (NOT) and the accessory optic system (AOS), which are known to represent the initial stage of the optokinetic pathways.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00228188
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  • 28
    Electronic Resource
    Electronic Resource
    Transmission from group II muscle afferents is depressed by stimulation of locus coeruleus/subcoeruleus, Kölliker-Fuse and raphe nuclei in the cat (1992)
    Springer
    Experimental brain research 88 (1992), S. 502-516 
    Details
    ISSN: 1432-1106
    Keywords: Locus coeruleus ; Kölliker-Fuse ; Raphe nuclei ; Synaptic transmission ; Spindle afferents ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effects of brief trains of electrical stimuli applied within the locus coeruleus and subcoeruleus, the Kölliker-Fuse nucleus and the raphe magnus, obscurus and pallidus nuclei were tested on transmission from group I and group II muscle afferent fibres in mid-lumbar spinal segments of chloralose anaesthetized cats. Changes in the effectiveness of transmission from these afferents were assessed from changes in the size of monosynaptic extracellular field potentials evoked by them. The depression of group II field potentials occurred at conditioning-testing intervals of 20–400 ms, and was maximal at intervals of 40–100 ms and 30–60 ms for potentials recorded in the intermediate zone and dorsal horn, respectively. At intervals up to about 30 ms it was combined with the depression of group I components of the intermediate zone field potentials. However, at longer intervals the conditioning stimuli depressed group II components of these potentials as selectively as monoamines applied ionophoretically at the recording site (Bras et al., 1989a, 1990). Thus, only the late depressive actions are considered as being possibly mediated by impulses in descending noradrenergic and/or serotonergic fibres. No major differences were found in the relative degree of depression of transmission from group II afferents by stimulation of the locus coeruleus/subcoeruleus, Kölliker-Fuse or raphe nuclei, either in the dorsal horn or in the intermediate zone. Since field potentials at these locations are preferentially depressed by ionophoretic application of serotonin and noradrenaline (Bras et al., 1990), and since the locus coeruleus/subcoeruleus, Kölliker-Fuse and raphe nuclei are interconnected, the study leads to the conclusion that both noradrenergic and serotonergic descending pathways can be activated by stimuli applied within either of them. Selective depression of field potentials of group II origin was also evoked by stimulation at other sites, e.g. the periaqueductal grey and medullary reticular formation, when conditioning-testing intervals were sufficiently long. Such a depression is considered to be secondary to activation of neurones of the locus coeruleus/subcoeruleus, Kölliker-Fuse or raphe nuclei and attributed to the spread of current or transsynaptic activation of these neurones, or to stimulation of their axon collaterals outside the nuclei rather than to other descending medullo-spinal systems. The non-selective depression of field potentials evoked by group I and group II afferents at shorter conditioning-testing intervals is proposed to be due to actions of reticulo-spinal pathways.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00228180
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  • 29
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    Electronic Resource
    Dorsal column input to thalamic VL neurons: an intracellular study in the cat (1992)
    Springer
    Experimental brain research 88 (1992), S. 551-559 
    Details
    ISSN: 1432-1106
    Keywords: Thalamus ; Motor cortex ; Dorsal column nuclei ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary This study investigated the role of the ventral lateral (VL) nucleus of the thalamus as a lemniscal relay to motor cortex. Intracellular recordings were obtained from thalamic VL relay neurons in cats anesthetized with chloralose, following stimulation of the dorsal column nuclei. VL neurons were identified by their short-latency input from the cerebellar nuclei, their antidromic activation from motor cortex and their anatomical location. A total of 105 neurons was studied. The occurence of temporal facilitation to double volleys was also examined. It was found that 80/105 (75%) neurons responded with excitation and/or inhibition to stimulation of the dorsal column nuclei. The latencies of the postsynaptic responses ranged from 2.0 to 20 ms (median 10.0 ms). The latencies of nearly all responses (79/80) were 〉 3 ms and nearly all responses (45/47) which were tested for it, displayed temporal facilitation to double shock stimulation, consistent with polysynaptic transmission. Effective stimulation sites were found in the gracile and cuneate nuclei. Recording sites were located throughout VL, including the “border region” with the ventral posterior lateral nucleus (VPL). There was no obvious topographic relationship between location of recording site and latency or polarity (excitation versus inhibition) of the synaptic responses. This is consistent with dorsal column input diffusely distributed over VL. When the recording electrodes penetrated VPL, characteristics of the EPSPs were indicative of monosynaptic transmission (short latency, no temporal facilitation). This clear transition from VL to VPL suggests that it is not necessary to define, on physiological grounds, a separate “border region” between these two nuclei. The data provide evidence that dorsal column information reaches VL neurons polysynaptically, not monosynaptically. This indicates that VL is part of a long-latency, not short-latency path through the dorsal column nuclei to motor cortex.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00228184
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  • 30
    Electronic Resource
    Electronic Resource
    Mono- and disynaptic pathways from Forel's field H to dorsal neck motoneurones in the cat (1992)
    Springer
    Experimental brain research 88 (1992), S. 580-593 
    Details
    ISSN: 1432-1106
    Keywords: Forel's field H ; Reticular formation ; Reticulospinal neurones ; Neck motoneurones ; Head movements ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 1. We analysed the synaptic actions produced by Forel's field H (FFH) neurones on dorsal neck motoneurones and the pathways mediating the effects. 2. Stimulation of ipsilateral FFH induced negative field potentials of several hundred microvolts with the latency of about 1.1 ms in the medial ponto-medullary reticular formation, being largest in the ventral part of the nucleus reticularis pontis caudalis (NRPC), and in the dorsal part of the nucleus reticularis gigantocellularis (NRG). 3. Stimulation of ipsilateral FFH induced excitatory postsynaptic potentials (EPSPs) in 90% (47/52) and inhibitory postsynaptic potentials (IPSPs) in 19% (10/52) of the reticulospinal neurones (RSNs) in the NRPC and the NRG. Latencies of the EPSPs and IPSPs were 0.7–3.0 ms, the majority of which were in the monosynaptic range. The monosynaptic connexions were confirmed by spike triggered averarging technique both in excitatory (n=4) and inhibitory (n=2) pathways. 4. Single stimulation of FFH induced EPSPs at the segmental latencies of 0.3–1.0 ms in neck motoneurones, which were clearly in the monosynaptic range. Repetitive stimulation of FFH produced marked temporal facilitation of EPSPs in neck motoneurones. The facilitated components of the EPSPs had a little longer latencies and their amplitude reached several times as large as that evoked by single stimulation in all the tested motoneurones. These facilitated excitations are assumed to be mediated by RSNs in the NRPC and NRG, since RSNs were mono- and polysynaptically fired by stimulation of FFH and they were previously shown to directly project to neck moteneurones. 5. EPSPs were induced in 91% (82/91) of motoneurones supplying m. biventer cervicis and complexus (BCC; head elevator), 10% (3/29) of motoneurones supplying m. splenius (SPL; lateral head flexor). Eikewise, stimulation of FFH produced EMG responses in BCC muscles, while not in SPL muscle. Thus FFH neurones produce excitations preferentially in BCC motoneurones. 6. Systematic tracking in and around FFH revealed that the effective sites for evoking above effects were in FFH and extended caudally along their efferent axonal course. 7. These results suggested that FFH neurones connect with neck motoneurones (chiefly BCC, head elevator) mono-, diand/or polysynaptically and are mainly concerned with the control of vertical head movements.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00228187
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  • 31
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    Electronic Resource
    Short latency cutaneous reflex responses of γ-efferents in the decerebrate cat (1992)
    Springer
    Experimental brain research 89 (1992), S. 140-146 
    Details
    ISSN: 1432-1106
    Keywords: Fusimotor neurones ; Muscle spindles ; Spinal reflexes ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effect of single shock stimulation, up to 20 × threshold (T), of the sural nerve on the discharges of triceps surae γ-efferents was investigated in decerebrate cats. Units were classified as static (12) or dynamic (7) on the basis of their resting discharge rates (Murphy et al. 1984). All neurones were excited at short latency by sural nerve stimulation and response size was graded with stimulus intensity. Short latency mixed or inhibitory responses were not evident. Although reflex effects first occurred at low stimulus strengths (〈-1.5T) in both types of efferent, most responses appeared at higher intensities (〉 1.5T). The estimated central delays of the responses of static (3.0 ±1.1 ms, mean± SD) and dynamic (3.4 ± 1.0 ms) γ-motoneurones were not significantly different and are consistent with spinal oligosynaptic pathways. The present results differ from those of the only previous study (Johansson and Sojka 1985) of the short latency responses of triceps surae static and dynamic γ-motoneurones to sural nerve stimulation, in which mixed and inhibitory effects were common in anaesthetised cats. Although differences in recording techniques and γ sampling may account for the apparent disparity between these studies, it is also feasible that a difference in the setting of interneuronal pathways in the two types of preparation is responsible. The results are discussed in relation to the control of γ-motoneurones with particular reference to the “final common input” hypothesis (Johansson 1981; Appelberg et al. 1983).
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00229011
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    Vocalizations in the cat: behavioral methodology and spectrographic analysis (1992)
    Springer
    Experimental brain research 89 (1992), S. 333-340 
    Details
    ISSN: 1432-1106
    Keywords: Animal model ; Vocalization ; Spectrograms ; Instrumental conditioning ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Attempts to understand the neural mechanisms underlying mammalian vocal behaviors, including speech, require study of the neural activity and anatomy of vocalization-controlling brain structures. Such studies necessitate the application of invasive neurobiological techniques in animal models. In the current study, cats are used in the development of an animal model of vocal tract control. The animals are instrumentally conditioned to vocalize for food reward. Acquisition of this task can occur within a few minutes, although additional training generally is required to solidly establish the behavior and to train subjects to produce consistently high rates of vocalization for prolonged periods of time. Following training, animals can generally sustain a rate of two calls per minute for a period of over two hours. Optimal task performance is partly dependent on motivation level. Although there is considerable variation between animals, the vocalizations produced have an average duration of 600 ms and a fundamental frequency of around 500 Hz. In addition, during a typical vocalization, there are dynamic variations of about 150 Hz for fundamental frequency and 17 dB for sound intensity. These variations provide opportunities for relating neural and muscular activity to different aspects of the vocal behavior they control. Based on a number of considerations, the model and techniques discussed here probably are most applicable to studying the neurobiology of sub-cortical nuclei subserving vocal control. Similar mechanisms might well be present in other species, including humans. Thus, data obtained from study of this model may be applicable to understanding the processes underlying vocal tract control during human speech.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00228249
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    Somatotopic termination of the spino-olivary fibers in the cat, studied with the wheat germ agglutinin-horseradish peroxidase technique (1992)
    Springer
    Experimental brain research 89 (1992), S. 397-407 
    Details
    ISSN: 1432-1106
    Keywords: Spinal cord ; Inferior olivary nucleus ; Somatotopy ; Wheat germ agglutinin horseradish peroxidase ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Terminal sites of the spino-olivary fibers (SOFs) were examined by the anterograde transport of wheat germ agglutinin-horseradish peroxidase in the cat. The tracer was injected at various spinal cord levels from the first cervical to the caudal segments. The SOFs derived from the C1-T1 segments terminated medially in the caudal half (levels II–VIII of Brodal) of the medial accessory olive (MAO), which projects to the A zone of the cerebellar cortex, whereas the SOFs derived from the L6-S1 segments terminated laterally in the caudal half (levels I–VIII) of the MAO. No projections were found from the T2-L5 segments to the MAO. In the dorsal accessory olive (DAO), the SOFs terminated at levels III–XIV; the DAO projects to the B zone and the C1 and C3 zones of the cerebellar cortex. The SOFs derived from the C1-C4 segments terminated in the most medial part of the DAO (levels III–XIV), followed laterally by those from the C5-T1 segments. Further laterally, the SOFs derived from the T2-L5 and the L6-S1 segments terminated in the mediolateral order at levels V–XIV. The SOFs from the L6-S1 segments occupied the most lateral part of the DAO. The present study demonstrates that there is a distinct somatotopic termination of the SOFs in the mediolateral order in the caudal MAO and the DAO.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00228255
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    The bulbar network of respiratory neurons during apneusis induced by a blockade of NMDA receptors (1992)
    Springer
    Experimental brain research 89 (1992), S. 623-639 
    Details
    ISSN: 1432-1106
    Keywords: Respiratory neurons ; Apneusis ; Rhythmogenesis ; Excitatory amino acid ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Our aim was to study the mechanisms producing the transition from the inspiratory phase to the expiratory phase of the breathing cycle. For this purpose we observed the changes affecting the discharge patterns and excitabilities of the different types of respiratory neurons within the respiratory network in cat medulla, after inducing an apneustic respiration with the N-methyl-D-aspartate (NMDA) antagonist MK-801 given systemically. Respiratory neurons were recorded extracellularly through the central barrel of multibarrelled electrodes, in the ventral respiratory area of pentobarbital-anesthetized, vagotomized, paralyzed and ventilated cats. Inhibitions exerted on each neuron by the presynaptic pools of respiratory neurons were revealed when the neuron was depolarized by an iontophoretic application of the excitatory amino-acid analogue quisqualate. Cycle-triggered time histograms of the spontaneous and quisqualate-increased discharge of respiratory neurons were constructed in eupnea and in apneusis induced with MK-801. During apneustic breathing, the activity of the respiratory neuronal network changed throughout the entire respiratory cycle including the post-inspiratory phase, and the peak discharge rates of all types of respiratory neurons, except the late-expiratory type, decreased. During apneusis, the activity of the post-inspiratory neuronal pool, the post-inspiratory depression of other respiratory neurons, and the phrenic nerve after-discharge were reduced (but not totally suppressed), whereas the discharge of some post-inspiratory neurons shifted into the apneustic plateau. The shortened post-inspiration (stage 1 of expiration) altered the organization of the expiratory phase. Late-expiratory neurons (stage 2 of expiration) discharged earlier in expiration and their discharge rate increased. The inspiratory on-switching was functionally unaffected. Early inspiratory neurons of the decrementing type retained a decrementing pattern followed by a reduced discharge rate in the apneustic plateau, whereas early-inspiratory neurons of the constant type maintained a high discharge rate throughout the apneustic plateau. Inspiratory augmenting neurons, late-inspiratory and “offswitch” neurons also discharged throughout the apneustic plateau. During the apneustic plateau, the level of activity was constant in the phrenic nerve and in inspiratory neurons of the early-constant, augmenting, and late types. However, progressive changes in the activity of other neuronal types demonstrated the evolving state of the respiratory network in the plateau phase. There was a slowed but continued decrease of the activity of early-inspiratory decrementing neurons, accompanied by an increasing activity and/or excitability of “off-switch”, postinspiratory and late-expiratory neurons. In apneusis there was a decoupling of the duration of inspiration and expiration. The variability of inspiratory duration increased five-fold whereas the variability of expiration was unchanged. We conclude that in the apneustic state, (1) inspiratory on-switching and the successive activation of the different inspiratory neuronal types are preserved; (2) near the end of the inspiratory ramp, the reversible phase of inspiratory off-switching is prolonged, producing the apneustic plateau, and (3) the irreversible phase of offswitching is impaired by a reduced activity of postinspiratory neurons. These results support the 3-phase model of respiratory rhythm generation, in which key roles are played by early-inspiratory and post-inspiratory neurons.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00229887
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    Sprouting of fusimotor neurones after partial denervation of the cat soleus muscle (1992)
    Springer
    Experimental brain research 90 (1992), S. 369-374 
    Details
    ISSN: 1432-1106
    Keywords: Muscle spindle ; Fusimotor ; Extrafusal ; Motor unit ; Contraction ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Normally, γ motoneurones innervate only the intrafusal fibres of muscle spindles. This is a report of sprouting of γ motoneurones to innervate extrafusal muscle fibres following partial denervation of the soleus muscle of kittens. In eight newborn animals, the L7 ventral root was cut on one side under anaesthesia and the animals were then allowed to recover. At approximately 100 days of age animals were reanaesthetised and a study made of mechanical properties of motor units whose axons ran in the S1 ventral root and supplied the partially denervated soleus muscle. Evidence was obtained for sprouting of all surviving α motoneurones. In addition, in four experiments axons conducting within the γ range, on stimulation, produced measurable tension. In one experiment, stimulation of one such γ axon also produced specific fusimotor effects on four afferents identified as coming from primary endings of muscle spindles. The γ axon was therefore a fusimotor axon. The effect observed on stimulation of the γ axon suggested a largely dynamic action. Other examples of γ axons were encountered that on stimulation produced tension, but which could not be specifically associated with spindles. In addition, a number of γ axons that did not develop tension were shown, on stimulation, to have fusimotor effects that were static in action. It is concluded that in extensively denervated muscles γ motoneurones may sometimes sprout to innervate extrafusal fibres. The mechanical properties of the extrafusal fibres innervated by such γ axons were similar to those of ordinary α motor units.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00227250
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    On the regulation of repetitive firing in lumbar motoneurones during fictive locomotion in the cat (1992)
    Springer
    Experimental brain research 90 (1992), S. 441-455 
    Details
    ISSN: 1432-1106
    Keywords: Afterhyperpolarisation ; Motoneurone ; Fictive locomotion ; Repetitive firing ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Repetitive firing of motoneurones was examined in decerebrate, unanaesthetised, paralysed cats in which fictive locomotion was induced by stimulation of the mesencephalic locomotor region. Repetitive firing produced by sustained intracellular current injection was compared with repetitive firing observed during fictive locomotion in 17 motoneurones. During similar interspike intervals, the afterhyperpolarisations (AHPs) during fictive locomotion were decreased in amplitude compared to the AHPs following action potentials produced by sustained depolarising current injections. Action potentials were evoked in 10 motoneurones by the injection of short duration pulses of depolarising current throughout the step cycles. When compared to the AHPs evoked at rest, the AHPs during fictive locomotion were reduced in amplitude at similar membrane potentials. The post-spike trajectories were also compared in different phases of the step cycle. The AHPs following these spikes were reduced in amplitude particularly in the depolarised phases of the step cycles. The frequency-current (f-I) relations of 7 motoneurones were examined in the presence and absence of fictive locomotion. Primary ranges of firing were observed in all cells in the absence of fictive locomotion. In most cells (6/7), however, there was no relation between the amount of current injected and the frequency of repetitive firing during fictive locomotion. In one cell, there was a large increase in the slope of the f-I relation. It is suggested that this increase in slope resulted from a reduction in the AHP conductance; furthermore, the usual elimination of the relation is consistent with the suggestions that the repetitive firing in motoneurones during fictive locomotion is not produced by somatic depolarisation alone, and that motoneurones do not behave as simple input-output devices during this behaviour. The correlation of firing level with increasing firing frequency which has previously been demonstrated during repetitive firing produced by afferent stimulation or by somatic current injection is not present during fictive locomotion. This lends further support to the suggestion that motoneurone repetitive firing during fictive locomotion is not produced or regulated by somatic depolarisation. It is suggested that although motoneurones possess the intrinsic ability to fire repetitively in response to somatic depolarisation, the nervous system need not rely on this ability in order to produce repetitive firing during motor acts. This capability to modify or bypass specific motoneuronal properties may lend the nervous system a high degree of control over its motor output.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00230927
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    Differential action of (−)-baclofen on the primary afferent depolarization produced by segmental and descending inputs (1992)
    Springer
    Experimental brain research 91 (1992), S. 29-45 
    Details
    ISSN: 1432-1106
    Keywords: Presynaptic inhibition ; Primary afferent depolarization ; Baclofen ; GABA ; Spinal cord ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The purpose of the present series of experiments was to analyze, in anesthetized and paralyzed cats, the effects of (-)-baclofen and picrotoxin on the primary afferent depolarization (PAD) generated in single Ib afferent fibers by either intraspinal microstimulation or stimulation of the segmental and descending pathways. PAD was estimated by recording dorsal root potentials and by measuring the changes in the intraspinal activation threshold of single Ib muscle afferent fibers. The PAD elicited by stimulation of group I muscle or cutaneous afferents was readily depressed and often abolished 20–40 min after the intravenous injection of 1–2 mg/kg (-)-baclofen. In contrast, the same amounts of (-)-baclofen produced a relatively small depression of the PAD elicited by stimulation of the brainstem reticular formation (RF). The monosynaptic PAD produced in single Ib fibers by intraspinal microstimulation within the intermediate nucleus was depressed and sometimes abolished following the i.v. injections of 1–2 mg/kg (-)-baclofen. Twenty to forty minutes after the i.v. injection of picrotoxin (0.5–1 mg/kg), there was a strong depression of the PAD elicited by stimulation of muscle and cutaneous afferents as well as of the PAD produced by stimulation of the RF and the PAD produced by intraspinal microstimulation. The results obtained suggest that, in addition to its action on primary afferents, (-)-baclofen may depress impulse activity and/or transmitter release in a population of last-order GABAergic interneurons that mediate the PAD of Ib fibers. The existence of GABAb autoreceptors in last-order interneurons mediating the PAD may function as a self-limiting mechanism controlling the synaptic efficacy of these interneurons.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00230011
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    Peculiarities of inhibition in cat auditory cortex neurons evoked by tonal stimuli of various durations (1992)
    Springer
    Experimental brain research 91 (1992), S. 115-120 
    Details
    ISSN: 1432-1106
    Keywords: Auditory cortex ; Tone ; Inhibition ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The extra- and intracellular responses of 262 neurons in A1 to tones of best frequency with durations ranging from 10 ms to 1.2 min were studied acute experiments on ketamine-anesthetized cats. Following the generation of action potentials in response to the tone stimulus, inhibition of both the background and the auditory stimulus-evoked spike activity were observed in 91% of the investigated neurons. The duration of this inhibition corresponded to the stimulus duration. For the remaining neurons (9%) an inhibition of the stimulus-evoked spike activity alone was seen, also corresponding to the stimulus duration. Maximal inhibition of the spike activity occurred for the first 100–200 ms of the inhibitory response (the period which equalled the time of development of an IPSP in a cell). During this period of IPSP development, the membrane resistance of the neuron was reduced to 60–90% of its initial value. Varying the duration of the acoustic signal within a range of 10–200 ms was accompanied by a change in the IPSP duration and inhibition of the spike acitivity of the neuron. Whenever the tone lasted more than 200 ms, the membrane potential of the neuron was restored to the resting potential. However, during this period, the responsiveness of the neuron was lower than that initially observed. Measurement of the membrane resistance during the inhibitory pause that was not accompanied by hyperpolarization produced an index with an average 17% lower than the initial value for 87% of the neurons. The data indicate that inhibition of the spike activity in Al neurons evoked by tone stimuli of various durations is due to the appearance of postsynaptic inhibition on their membrane. It is concluded that the time course of the cortical inhibitory input to neurons is the major factor determining variations in duration of the inhibition of response of auditory cortex neurons to an auditory stimulus.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00230019
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    Differences between steady-state and transient post-synaptic potentials elicited by stimulation of the sural nerve (1992)
    Springer
    Experimental brain research 91 (1992), S. 167-170 
    Details
    ISSN: 1432-1106
    Keywords: Motoneurons ; Post-synaptic potential ; Sural nerve ; Recruitment ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In cat medial gastrocnemius motoneurons, single stimuli to the cutaneous sural nerve evoke a post-synaptic potential with a mixture of depolarization and hyperpolarization, depolarization being dominant in type F cells and hyperpolarization in type S cells. This pattern is consistent with previous reports showing that activation of the sural nerve can sometimes reverse the normal order of motor unit recruitment by inhibiting S motor units while simultaneously exciting F motor units. However, during repetitive stimulation for 1–2 s, we found that the hyperpolarizing component of the sural input to medial gastrocnemius motoneurons was not persistent, but instead gave way to depolarization after the first 30 ms. The net steady-state response after 0.5–1.0 s of stimulation was depolarization in all cells, regardless of motor unit type. This suggests that tonic sural input may be incapable of producing prolonged recruitment reversals.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00230025
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  • 40
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    Pretectal jerk neuron activity during saccadic eye movements and visual stimulations in the cat (1992)
    Springer
    Experimental brain research 91 (1992), S. 273-283 
    Details
    ISSN: 1432-1106
    Keywords: Pretectum ; Jerk neurons ; Saccades ; Visual stimuli ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The activity of ‘jerk neurons’ was recorded extracellularly in the pretectum of the awake cat. The characteristic response of jerk neurons was a short, high-frequency burst that occurred after fast movements (‘jerks’) of a large, structured visual stimulus, during saccadic eye movements in the light, and after ‘on’ or ‘off’ visual stimulation. Mean burst latency to pure visual ‘jerks’ was 50 ms, whereas it was 30 ms to saccadic eye movements. Bursts were found to be stereotyped; the highest discharge rate was always at burst onset. Jerk neurons were not selective for stimulus parameters (such as movement amplitude or direction) except that in some neurons a weak correlation between stimulus velocity and discharge frequency was found. During saccades in the dark, clear bursts were only rarely found. In about half of the neurons, however, there was a slight but significant increase in the number of spikes above spontaneous frequency. Visual receptive fields were very large (46° horizontal and 35° vertical extent, on average). Nevertheless, the pretectal jerk neurons showed a rough retinotopic order, which was in accordance with the published retinotopy of the pretectum. Jerk neurons were found throughout the whole superficial pretectum, but preferentially in an area that corresponds to the nucleus of the optic tract (NOT) and the nucleus pretectalis posterior (NPP). Saccades were elicited by electrical stimulations at the sites where jerk neurons were recorded. The direction of the elicited saccades depended strongly on the pretectal stimulation site. A possible role of the jerk neurons as a visuomotor relay to elicit saccades or to modulate perception and attention is discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00231660
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    Expression of GAP-43 mRNA in the adult mammalian spinal cord under normal conditions and after different types of lesions, with special reference to motoneurons (1992)
    Springer
    Experimental brain research 91 (1992), S. 284-295 
    Details
    ISSN: 1432-1106
    Keywords: GAP-43 ; In situ hybridization ; Spinal cord ; Axotomy ; Rat ; Cat ; Monkey
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In situ hybridization histochemistry was used to detect cell bodies expressing mRNA encoding for the phosphoprotein GAP-43 in the lumbosacral spinal cord of the adult rat, cat and monkey under normal conditions and, in the cat and rat, also after different types of lesions. In the normal spinal cord, a large number of neurons throughout the spinal cord gray matter were found to express GAP-43 mRNA. All neurons, both large and small, in the motor nucleus (Rexed's lamina IX) appeared labeled, indicating that both alpha and gamma motoneurons express GAP-43 mRNA under normal conditions. After axotomy by an incision in the ventral funiculus or a transection of ventral roots or peripheral nerves, GAP-43 mRNA was clearly upregulated in axotomized motoneurons, including both alpha and gamma motoneurons. An increase in GAP-43 mRNA expression was already detectable 24 h postoperatively in lumbar motoneurons both after a transection of the sciatic nerve at knee level and after a transection of ventral roots. At this time, a stronger response was seen in the motoneurons which had been subjected to the distal sciatic nerve transection than was apparent for the more proximal ventral root lesion. An upregulation of GAP-43 mRNA could also be found in intact motoneurons located on the side contralateral to the lesion, but only after a peripheral nerve transection, indicating that the concomitant influence of dorsal root afferents may play a role in GAP-43 mRNA regulation. However, a dorsal root transection alone did not seem to have any detectable influence on the expression of GAP-43 mRNA in spinal motoneurons, while the neurons located in the superficial laminae of the dorsal horn responded with an upregulation of GAP-43 mRNA. The presence of high levels of GAP-43 in neurons has been correlated with periods of axonal growth during both development and regeneration. The role for GAP-43 in neurons under normal conditions is not clear, but it may be linked with events underlying remodelling of synaptic relationships or transmitter release. Our findings provide an anatomical substrate to support such a hypothesis in the normal spinal cord, and indicate a potential role for GAP-43 in axon regeneration of the motoneurons, since GAP-43 mRNA levels was strongly upregulated following both peripheral axotomy and axotomy within the spinal cord. The upregulation of GAP-43 mRNA found in contralateral, presumably uninjured motoneurons after peripheral nerve transection, as well as in dorsal horn neurons after a dorsal root transection, indicates that GAP-43 levels are altered not only as a direct consequence of a lesion, but also after changes in the synaptic input to the neurons.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00231661
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    Decreasing the cortical response to monocular deprivation need not decrease cell shrinkage in cat lateral geniculate nucleus (1992)
    Springer
    Experimental brain research 92 (1992), S. 79-84 
    Details
    ISSN: 1432-1106
    Keywords: Visual cortex ; Norepinephrine ; Acetylcholine ; Critical and sensitive periods ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Monocular deprivation (MD) of young kittens decreases the response of visual cortex cells to the deprived eye. In addition, it causes cell shrinkage in the layers of the lateral geniculate nucleus (LGN) innervated by the deprived eye. To determine whether the shrinkage of LGN cells is dependent upon changes in the response of cortical cells, we compared LGN cell shrinkage in three groups of MD animals. Two were controls; the third received lesions of fibers bringing norepinephrine and acetylcholine to the visual cortex. This procedure greatly attenuated the effect of MD on the visual cortex. The amount of LGN cell shrinkage did not differ among the three groups. We conclude that LGN shrinkage after MD does not require a dramatic loss of cortical cell responses to the deprived eye.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00230385
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    Functional topography of cat primary auditory cortex: representation of tone intensity (1992)
    Springer
    Experimental brain research 92 (1992), S. 105-122 
    Details
    ISSN: 1432-1106
    Keywords: Primary auditory cortex ; Intensity ; Isofrequency domain ; Topography ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The neuronal response to tones as a function of intensity was topographically studied with multiple-unit recordings in the primary auditory cortex (AI) of barbiturate-anesthetized cats. The spatial distribution of the characteristics of rate/level functions was determined in each of three intensely studied cases and their relationship to the distribution of spectral parameters (sharpness of tuning and responses to broadband transients) in the same animals was determined. The growth of the high-intensity portion of rate/level functions was estimated by linear regression. Locations with monotonically growing high-intensity portions were spatially segregated from locations with nonmonotonic rate/level functions. Two noncontiguous areas with a high degree of non-monotonicity were observed. One was located at the dorsoventral center of AI, and a second in the dorsal third of AI. The more ventral aggregate of high non-monotonicity coincided with the region of sharp frequency tuning. The stimulus levels that produced the highest firing rate (strongest response level, SRL) at any sampled location ranged from 10 to 80 dB sound pressure level (SPL). Several spatial aggregates with either high or low SRLs were observed in AI. The region of sharpest tuning was always associated with a region of low SRLs. The response threshold to contralateral tones at the characteristic frequency (CF) ranged from — 10 dB SPL to 85 dB SPL with the majority between 0 and 40 dB SPL. The spatial distribution of response thresholds indicated several segregated areas containing clusters with either higher or lower response thresholds. The correlation of response threshold with integrated bandwidth and transient responses was only weak. Low- and high-intensity tones of the same frequency are represented at different locations in AI as judged by the amount of evoked neuronal activity and are largely independent of the frequency organization. The spatial distribution of locations with high monotonicity and low strongest response levels were aligned with the organization of the integrated excitatory bandwidth and covaried with the response strength to broadband stimuli.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00230388
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    Responses of cat ventroposterolateral thalamic neurons to vibrotactile stimulation of forelimb footpads (1992)
    Springer
    Experimental brain research 92 (1992), S. 286-298 
    Details
    ISSN: 1432-1106
    Keywords: Somatosensory thalamus ; Vibrotactile sensation ; Tactile neurons ; Vibration coding ; Glabrous skin ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Responses of neurons in the ventroposterolateral nucleus of the thalamus to vibration applied to the forelimb footpads were analyzed in anesthetized cats in order to describe the signalling properties of thalamic neurons that received input from the different classes of tactile afferents innervating the glabrous skin of the distal forelimb. Seventy-six thalamic neurons, the majority of which (60 of 76) were positively identified as thalamocortical projection neurons, were classified into two broad groups according to their responses to 1-s step indentations of the skin. A minority (24%) comprised neurons that had slowly adapting (SA) responses, whereas the remainder (76%), the dynamically sensitive neurons, had transient responses to the onset and offset phase of the step and were further classified according to their sensitivity to cutaneous vibrotactile stimuli into those activated by low-frequency vibration (rapidly adapting, RA, neurons) and those activated by high frequencies (Pacinian afferent, PC, neurons). Thalamic RA neurons displayed phaselocked responses to vibration at frequencies up to ∼100 Hz, while PC neurons displayed phaselocked responses to vibration up to 400–500 Hz. Thalamic SA neurons varied in their responses to vibrotactile stimuli; half were most sensitive to vibration frquencies of 50 Hz or less, while the others responded over a broader range of frequencies. Although three major classes of footpad-related thalamic neurons were identified, there was evidence of convergent input to a small proportion of them. The study demonstrates that thalamic neurons have the capacity for responding to cutaneous vibration with phaselocked, patterned impulse trains, which would enable them to encode information about vibrotactile frequencies up to ∼ 300 Hz.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00227971
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    Electromyographic studies of neck muscles in the intact cat (1992)
    Springer
    Experimental brain research 88 (1992), S. 41-58 
    Details
    ISSN: 1432-1106
    Keywords: Head movement ; Electromyography ; Muscle activity ; Cervical vertebrae ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Natural head movements in alert, unrestrained cats were studied using video-filming, videofluoroscopy and electromyographic (EMG) recording methods. In each cat, up to sixteen neck muscles or neck-muscle compartments were implanted with recording electrodes. Patterns of muscle recruitment were examined during systematically-selected behavioral epochs in which the cat held a range of stationary postures, and when it performed volitional and exploratory behaviors such as flexion-extension or turning, grooming, eating, or headshaking. Patterns of muscular activity were interpreted with reference to simultaneous video images of head and neck movements. In separate, videofluoroscopic analysis, flexion-extension movements were examined to gain insight into the underlying movements of the skull and cervical vertebrae. These and other movements were found commonly to depend upon changes in joint angles between lower as well as upper cervical joints. Stationary postures in which the neck was held vertically were consistently associated with tonic EMG activity in only two long dorsal muscles, biventer cervicis and occipitoscapularis. Less consistent activity was also present in dorsal intervertebral muscles crossing lower cervical joints. When the neck was held horizontally, the long dorsal muscles increased their EMG activity and moderate activity was also recorded in deeper intervertebral and suboccipital muscles. When flexion-extension occurred around upper cervical joints, greatest activity was recorded in rectus capitis posterior and complexus, but when it involved the lower cervical joints, large changes in EMG activity could also be detected in biventer cervicis, occipitoscapularis, and the intervertebral muscles crossing lower cervical joints. During specialized, sagittal-plane movements such as grooming, well-defined patterns of synergy could be recognized that varied according to the degree of involvement of upper and lower cervical joint-sets. Movements in the horizontal plane were associated with EMG activity in a largely different subset of neck muscles including splenius, longissimus capitis and obliquus capitis inferior. The levels of EMG activity during flexion-extension or turning movements were much lower than those observed during other more vigorous behaviors, such as head shaking. Some neck muscles, such as clavotrapezius and sternomastoideus, could only be recruited during forceful or ballistic head movements. Results showed that the patterns of muscular activation were linked not only to the speed and trajectory of the movements of the skull, but also to the kinematics of the motion occurring across different parts of the cervical column.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02259127
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    Biomechanical organization of single motor units in two multi-tendoned muscles of the cat distal forelimb (1992)
    Springer
    Experimental brain research 88 (1992), S. 411-421 
    Details
    ISSN: 1432-1106
    Keywords: Motor unit ; Multi-tendoned muscle ; Mechanical partitioning ; Mechanical cross-coupling ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In anesthetized cats single motor units (MUs) of the extensor carpi ulnaris (ECU) and extensor digitorum communis (EDC) muscles were selectively activated by stimulation of cervical ventral root filaments. The distribution of force developed by single MUs at the four distal tendons of the EDC muscle and at three portions of the distal tendon of the ECU muscle was analysed. In general, single MUs of both muscles distributed force over all tendons in a unimodal pattern, with the maximal force levels generated at one specific tendon which was termed the best-tendon. Distributions of force were quantitatively described by a parameter representing the mean direction of force output (output-index) and a further one representing the dispersion of force over the distal tendons (divergence). Generally, these parameters and the best-tendon remained stable when a MU was stimulated at different frequencies, but varied from MU to MU. Despite the general stability of the force distribution, slight systematic changes were regularly found in EDC MUs, when they developed a higher amount of force due to a higher frequency of stimulation: the relative amount of force at the best-tendon increased; e.g. the MUs got more selective for the best-tendon. These changes were partly due to overcoming mechanical cross-coupling between neighbouring compartments of the EDC muscle. Such changes of force distribution were only found in a part of the ECU MUs; other ECU MUs did not change their force distribution at all or became less selective for the best-tendon. The phenomenon that MUs of multi-tendoned muscles distribute their force output to the distal tendons in specific patterns is probably due to mechanical partitioning of the parent muscles: the localization of spatial territories of MUs within different anatomical muscle compartments should correspond to the best-tendon. Complex mechanisms allowing passive transmission of force from limited territories along the transverse axis of both muscles must be assumed in order to explain why most MUs act on all tendons and why force distributions change with increasing stimulus frequency. In addition, specific relations between unit type and force distributions were found within both muscles. Fatigue-resistant EDC MUs have broader force distributions than fatigue-sensitive EDC MUs and slow ECU MUs were found to act predominantly on the most ulnar part of the distal tendon. These biomechanical properties of MUs are discussed as supporting the specific functions of the respective muscles.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02259116
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    Descending projections of Forel's field H neurones to the brain stem and the upper cervical spinal cord in the cat (1992)
    Springer
    Experimental brain research 88 (1992), S. 563-579 
    Details
    ISSN: 1432-1106
    Keywords: Forel's field H ; Diencephalon ; Reticular formation ; Neck motoneurone ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 1. Descending projections from Forel's field H (FFH) to the brain stem and upper cervical spinal cord were studied in cats. 2. Following implantation of HRP pellets into the spinal gray matter (C1-C3) or in the ponto-medullary reticular formation, the nucleus reticularis pontis caudalis (NRPC) or in the nucleus reticularis gigantocellularis (NRG), numerous neurones were retrogradely labelled in FFH on the ipsilateral side. In the former cases, the sizes of labelled neurones were medium-large (20μ40 μm in diametre) while both small and medium-large neurones were labelled in the latter cases. 3. The lowest levels of spinal projection of single FFH neurones (n=70) were assessed by antidromic spikes elicited by stimulating electrodes placed in C1, C3 and C7. The majority (59%) projected to C1 (but not to C3), about 27% to C3 (but not to C7), and only 14% to C7. 4. Axonal trajectories of single FFH neurones in C1-C3 segments were investigated by antidromic threshold mapping methods. The stem axons of spinal-projecting FFH neurones descended in the ventral or in the ventrolateral funicli and the collaterals were projected to neck motor nuclei (lamina IX, Rexed 1954) and laminae V–VIII. The conduction velocities were estimated as 8–37 m/s from the antidromic latencies. 5. Axonal trajectories of 7 FFH neurones were investigated in the ponto-medullary reticular formation. All were antidromically activated from C1. In six neurones, the stem axons were located in the ventral part of the central tegmental tract and collaterals were projected to the NRPC and/or the NRG. Some of them projected to the inferior olive and the nucleus prepositus hypoglossi as well. The stem axon, in the remaining cell, was in the most dorso-medial part of the medial longitudinal fasciculus and collaterals were projected mainly to the dorsal part of the NRPC and the NRG, and also to the medial vestibular nucleus. 6. Anterograde transport of WGA-HRP injected into FFH revealed that in the upper cervical spinal cord, stem axons were found in the ventral funiculus and ventral part of the lateral funiculus. Collateral projections and presumed bouton-like deposits were observed in the laminae VI–IX, especially in their medial part. In the brain stem, dense bundles of the descending fibres were found in the central and the medial tegmental tracts and in the medial longitudinal fasciculus. FFH neurones projected densely to the caudal half of the NRPC and to the rostral half of the NRG. Extremely dense projections to the inferior olive were noted.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00228186
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    Electronic Resource
    Coordination of the legs of a slow-walking cat (1992)
    Springer
    Experimental brain research 89 (1992), S. 147-156 
    Details
    ISSN: 1432-1106
    Keywords: Walking ; Interlimb coordination ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary On the basis of behavioural studies the influences that coordinate the movement of the legs of a slowly walking cat have been investigated. The recording method applied here allows for the measurement of forward and backward movement of the legs which are called swing and stance movements, respectively. Influences etween contralateral legs, i.e. both front legs or both hind legs, are stronger than those occurring between ipsilateral legs, i.e. front and hind leg of the same side. Influences which coordinate the front legs seem to be of the same kind as those for the hind legs. These influences are symmetrical, which means that the same type of influence acts from right to left leg and in the reverse direction. Two types of influences are described for contralateral legs: 1. When the influencing leg performs a swing movement, the influenced leg is prevented from starting a swing movement. 2. When the influencing leg performs a stance movement, the probability that the influenced leg starts a swing movement increases as the influencing leg moves backwards during its stance movement. In contrast to contralateral coupling, the ipsilateral influences are asymmetric, i.e. a different influence acts from front to hind leg than does in the reverse direction. The front leg is influenced to start a swing when both legs have approached each other to a given value. The hind leg is influenced to start a stance movement after the front leg has begun its swing.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00229012
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    Responses of neurons in the caudal medullary raphe nuclei of the cat to stimulation of the vestibular nerve (1992)
    Springer
    Experimental brain research 89 (1992), S. 323-332 
    Details
    ISSN: 1432-1106
    Keywords: Vestibular system ; Raphe nuclei ; Spinal cord ; Sympathetic nervous system ; Vestibulosympa ; thetic reflex ; Orthostatic hypotension ; Cardiovascular regulation ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In the decerebrate cat, recordings were made from neurons in the caudal medullary raphe nuclei to determine if they responded to electrical stimulation of the vestibular nerve and thus might participate in vestibulo-sympathetic reflexes. Many of these cells projected to the upper thoracic spinal cord. The majority (20/28) of raphespinal neurons with conduction velocities between 1 and 4 m/s received vestibular inputs; 13 of the 20 were inhibited, and 7 were excited. Since many raphespinal neurons with similar slow conduction velocities are involved in the control of sympathetic outflow, as well as in other functions, these cells could potentially relay vestibular signals to sympathetic preganglionic neurons. The onset latency of the vestibular effects was long (median of 15 ms), indicating the inputs were polysynaptic. In addition, 34 of 42 raphespinal neurons with more rapid conduction velocities (6–78 m/s) also received long-latency (median of 10 ms) labyrinthine inputs; 26 were excited and 8 were inhibited. Although little is known about these rapidlyconducting cells, they do not appear to be involved in autonomic control, suggesting that the function of vestibular inputs to raphe neurons is not limited to production of vestibulosympathetic reflexes. One hypothesis is that raphe neurons are also involved in modulating the gain of vestibulocollic and vestibulospinal reflexes; this possibility remains to be tested.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00228248
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  • 50
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    Electronic Resource
    Factors influencing neural activity in parabrachial regions during cat vocalizations (1992)
    Springer
    Experimental brain research 89 (1992), S. 341-351 
    Details
    ISSN: 1432-1106
    Keywords: Parabrachial region ; Vocalization ; Single-unit ; recordings ; Multiple-unit recordings ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The parabrachial nucleus in mammals is intimately connected with other vocalization controlling brainstem structures. It, along with ventromedially adjacent structures, also has been identified as the pneumotaxic center, and as such shows strong respiratory related activity in the anesthetized cat. The current study examines the neuronal activity in cat parabrachial regions during production of instrumentally conditioned vocalizations. Most of the units in our sample show considerable activity during periods between vocalizations. For many units, firing rate fluctuates during the respiratory cycle, although apparently not as strongly as reported in the decerebrate cat. Also, there is often strong phasic activity during periods where animals are licking to ingest their food rewards. During the peri-vocalization period, various neural activity patterns can be recorded. Most common is an activity increase during the vocalization itself. Moreover, in some units, this activity increase has an auditory component. A smaller number of units show other activity patterns, including a suppression of activity during vocalization and activity increases preceding the vocalization. Overall, our results suggest that the parabrachial region's involvement in vocal control is quite complex, involving convergence of respiratory, acoustic, vocalization-related, and perhaps somatosensory influences.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00228250
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    Two modes of cerebellar input to the parietal cortex in the cat (1992)
    Springer
    Experimental brain research 90 (1992), S. 241-252 
    Details
    ISSN: 1432-1106
    Keywords: Parietal cortex ; Thalamus ; Cerebellar nucleus ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The characteristics of cerebellar input to the parietal cortex through the ventroanterior-ventrolateral (VA-VL) complex of the thalamus were investigated in the adult cat by using combined electrophysiological and anatomical methods. Two distinct parietal regions were activated by stimulation of the cerebellar nuclei (CN). In the first region located in the depth of the bank of the ansate sulcus, stimulation of the CN induced early surface positive-deep negative potentials and late surface negative-deep positive potentials. In this cortical area, potentials of similar shape and time course were evoked at a shorter latency by stimulation of the ventrolateral part of the VA-VL complex where large negative field potentials were evoked by stimulation of the CN. After injection of the anterograde tracer Phaseolus vulgaris leucoagglutinin (PHA-L) in this part of the VA-VL complex, axon terminals of thalamocortical (TC) fibers were found in layers I, III and IV in the depth of the bank of the ansate sulcus and layers I and III in the motor cortex. In the second region located in the suprasylvian gyrus, late surface negative-deep positive potentials were evoked by stimulation of the CN and similar potentials were evoked at a shorter latency from the dorsomedial part of the VA-VL complex where large cerebellar-evoked potentials could be recorded. PHA-L injection in this thalamic region stained TC fibers and their terminals in layer I of the suprasylvian gyrus, and in layers I and III of the motor cortex. The laminar distribution of TC axon terminals in two different regions of the parietal cortex could account for the depth profiles of the cerebellar- and the thalamic-evoked potentials in each region. These results show that cerebellar information is conveyed to two separate areas in the parietal cortex by two different TC pathways.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00227235
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    Role of upper cervical inspiratory neurons studied by cross-correlation in the cat (1992)
    Springer
    Experimental brain research 90 (1992), S. 153-162 
    Details
    ISSN: 1432-1106
    Keywords: Respiration ; Neurons ; Axonal projections ; Spinal cord ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Axonal projections and synaptic connectivity of upper cervical inspiratory neurons (UCINs) were investigated in anaesthetised cats to clarify their role as propriospinal respiratory interneurons. Antidromic mapping showed axonal collaterals near phrenic and intercostal motonuclei. Of the UCINs tested, 37% had collaterals at T3-4; 55% had ipsilateral projections and 45% had contralateral projections. Ipsilateral or contralateral cross-correlations of the activity of pairs of UCINs (one on each side of the spinal cord) with the discharge of internal intercostal, external intercostal (T3-4) or phrenic nerves revealed similar features. Those with the internal intercostal and phrenic nerves were interpreted as evidence for shared or oligosynaptic excitation, those with the external intercostal nerve as shared excitation and inhibition. No evidence for monosynaptic connections was found. Monosynaptic connections could also not be demonstrated between inspiratory intercostal neurons located near (〈 0.5 mm) the UCINs collateral arborizations in T3-4, examined by cross-correlation. Afferent feedback from internal intercostal nerves (T3-4) was investigated by cross-correlating nerve stimulation with UCINs activity. Ipsilateral and contralateral cross-correlograms had similar features, providing evidence for excitation in some cases and inhibition in others. Finally, cross-correlations between ipsilateral UCINs and cervical sympathetic nerves were featureless. The results suggest that the role of UCINs as part of a respiratory propriospinal control system analagous to forelimb motor control is untenable, although they may be part of an intercostal afferent feedback loop.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00229267
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    Functional coupling of the stabilizing eye and head reflexes during horizontal and vertical linear motion in the cat (1992)
    Springer
    Experimental brain research 91 (1992), S. 191-206 
    Details
    ISSN: 1432-1106
    Keywords: Eye-head coordination ; Stabilizing reflexes ; Visual and otolith systems ; Sinusoidal linear motion ; Neck muscles ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The otolith contribution and otolith-visual interaction in eye and head stabilization were investigated in alert cats submitted to sinusoidal linear accelerations in three defined directions of space: up-down (Z motion), left-right (Y motion), and forward-back (X motion). Otolith stimulation alone was performed in total darkness with stimulus frequency varying from 0.05 to 1.39 Hz at a constant half peak-to-peak amplitude of 0.145 m (corresponding acceleration range 0.0014–1.13 g) Optokinetic stimuli were provided by sinusoidally moving a pseudorandom visual pattern in the Z and Y directions, using a similar half peak-to-peak amplitude (0.145 m, i.e., 16.1°) in the 0.025–1.39 Hz frequency domain (corresponding velocity range 2.5°–141°/s). Congruent otolith-visual interaction (costimulation, CS) was produced by moving the cat in front of the earth-stationary visual pattern, while conflicting interaction was obtained by suppressing all visual motion cues during linear motion (visual stabilization method, VS, with cat and visual pattern moving together, in phase). Electromyographic (EMG) activity of antagonist neck extensor (splenius capitis) and flexor (longus capitis) muscles as well as horizontal and vertical eye movements (electrooculography, EOG) were recorded in these different experimental conditions. Results showed that otolith-neck (ONR) and otolith-ocular (OOR) responses were produced during pure otolith stimulation with relatively weak stimuli (0.036 g) in all directions tested. Both EMG and EOG response gain slightly increased, while response phase lead decreased (with respect to stimulus velocity) as stimulus frequency increased in the range 0.25–1.39 Hz. Otolith contribution to compensatory eye and neck responses increased with stimulus frequency, leading to EMG and EOG responses, which oppose the imposed displacement more and more. But the otolith system alone remained unable to produce perfect compensatory responses, even at the highest frequency tested. In contrast, optokinetic stimuli in the Z and Y directions evoked consistent and compensatory eye movement responses (OKR) in a lower frequency range (0.025–0.25 Hz). Increasing stimulus frequency induced strong gain reduction and phase lag. Oculo-neck coupling or eye-head synergy was found during optokinetic stimulation in the Z and Y directions. It was characterized by bilateral activation of neck extensors and flexors during upward and downward eye movements, respectively, and by ipsilateral activation of neck muscles during horizontal eye movements. These visually-induced neck responses seemed related to eye velocity signals. Dynamic properties of neck and eye responses were significantly improved when both inputs were combined (CS). Near perfect compensatory eye movement and neck muscle responses closely related to stimulus velocity were observed over all frequencies tested, in the three directions defined. The present study indicates that eye-head coordination processes during linear motion are mainly dependent on the visual system at low frequencies (below 0.25 Hz), with close functional coupling of OKR and eye-head synergy. The otolith system basically works at higher stimulus frequencies and triggers Synergist OOR and ONR. However, both sensorimotor subsystems combine their dynamic properties to provide better eyehead coordination in an extended frequency range and, as evidenced under VS condition, visual and otolith inputs also contribute to eye and neck responses at high and low frequency, respectively. These general laws on functional coupling of the eye and head stabilizing reflexes during linear motion are valid in the three directions tested, even though the relative weight of visual and otolith inputs may vary according to motion direction and/or kinematics.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00231654
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    Corticocortical connections of cat primary somatosensory cortex (1992)
    Springer
    Experimental brain research 91 (1992), S. 425-434 
    Details
    ISSN: 1432-1106
    Keywords: SI ; SII ; Area 3b ; Area 2 ; Cytoarchitecture ; Forepaw ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The organization of corticocortical connections in the representation of the forepaw in cat primary somatosensory cortex (SI) was studied following injections of various tracers into different cortical cytoarchitectonic areas. Small injections of horseradish peroxidase, wheat germ agglutinin-conjugated HRP, Phaseolus vulgaris leukoagglutinin, or fast blue were placed into the representation of the forepaw in areas 3b, 1, or 2. The positions of labeled neurons in SI and the surrounding cortical areas were plotted on flattened surface reconstructions to determine the organization of the corticocortical connections within SI. A strong, reciprocal projection linked the two forepaw representations which have been described in area 3b and the part of area 2 which lies in the anterior bank of the lateral ansate sulcus (see Iwamura and Tanaka 1978a, b). Dense projections also linked these areas with SII, as previously reported (Burton and Kopf 1984a). Additional projections to area 3b arose primarily from areas 3a and 1. Projections to area 2 were more widespread than those to area 3b, and arose from all other areas of SI as well as from areas 4 and 5a. All injections into SI tended to label groups of neurons which lay in mediolateral strips. Corticocortical projection neurons which were most heavily labeled by SI injections were pyramidal cells in layer III. Additional projections from area 2 to 3b, area 5a to 2, and SII to areas 2 and 3b arose from layer VI as well. Although neurons of layers III and VI were always the most densely labeled, large injections into SI labeled neurons in layers II and V as well.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00227839
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    How complete is physiological compensation in extrastriate cortex after visual cortex damage in kittens? (1992)
    Springer
    Experimental brain research 91 (1992), S. 455-466 
    Details
    ISSN: 1432-1106
    Keywords: Brain damage ; Neural plasticity ; Striate cortex ; Extrastriate cortex ; Recovery of function ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Previous studies indicate that neurons in the cat's posteromedial lateral suprasylvian (PMLS) visual area of cortex show physiological compensation after neonatal but not adult damage to areas 17, 18, and 19 of the visual cortex (collectively, VC). Thus, VC damage in adults produces a loss of direction selectivity and a decrease in response to the ipsilateral eye among PMLS cells, but these changes are not seen in adult cats that received VC damage as kittens. This represents compensation for early VC damage in the sense that PMLS neurons develop properties they would have had if there had been no brain damage. However, this is only a partial compensation for the effects of VC damage. A full compensation would involve development of properties of the VC cells that were removed in the damage. The present study investigated whether this type of compensation occurs for detailed spatial- and temporal-frequency processing. Single-cell recordings were made in PMLS cortex of adult cats that had received a VC lesion on the day of birth or at 8 weeks of age. Responses to sine-wave gratings that varied in spatial frequency, contrast, and temporal frequency were assessed quantitatively. We found that the spatial- and temporal-frequency processing of PMLS cells in adult cats that had neonatal VC damage were not significantly different from PMLS cells in normal cats. Therefore, there was no evidence that PMLS cells can compensate for VC damage by developing properties that are better than normal and like those of the striate cortex cells that were damaged. We also assessed the effects of long-term VC damage in adult cats to determine whether the normal properties seen in cats with neonatal VC damage represent a compensation for abnormalities in PMLS cortex present after adult damage. In a previous study, we found that acute VC damage in adult cats has small but reliable effects on maximal response amplitude, maximal contrast sensitivity, and spatial resolution (Guido et al. 1990b). In the present study, we found that long-term VC damage in adult cats does not increase these abnormalities as a result of secondary degenerative changes. In fact, the minor abnormalities that were present after an acute VC lesion were virtually absent following a long-term adult lesion, perhaps because they were due to transient traumatic effects. Therefore, there was little evidence for abnormalities in spatial- or temporal-frequency processing following long-term adult VC damage for which PMLS cells might show compensation following long-term neonatal damage. Our results thus indicate that there is little or no difference in the spatial- or temporal-frequency processing of PMLS cells in normal cats and cats with long-term VC damage received early in life or as adults. These findings are discussed in relation to the inputs to PMLS cortex and to the behavioral abilities of cats with VC damage at different ages. The implications for under-standing the role of lateral suprasylvian visual cortex in behavioral recovery from VC damage is considered.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00227841
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    Trigeminal excitation of dorsal neck motoneurones in the cat (1992)
    Springer
    Experimental brain research 92 (1992), S. 183-193 
    Details
    ISSN: 1432-1106
    Keywords: Trigeminal afferents ; Trigeminospinal neurones ; Excitation ; Neck motoneurones ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Excitation of dorsal neck motoneurones evoked by electrical stimulation of primary trigeminal afferents in the Gasserian ganglion has been investigated with intracellular recording from α-motoneurones in the cat. Single stimulation in the Gasserian ganglion ipsi-and contralateral to the recording side evoked excitatory postsynaptic potentials (EPSPs) in motoneurones innervating the lateral head flexor muscle splenius (SPL) and the head elevator muscles biventer cervicis and complexus (BCC). The gasserian EPSPs were composed of early and late components which gave the EPSPs a hump-like shape. A short train of stimuli, consisting of two to three volleys, evoked temporal facilitation of both the early and late EPSP components. The latencies of the gasserian EPSPs ranged from 1.6 to 3.6 ms in SPL motoneurones and from 1.6 to 5.8 ms among BCC motoneurones. A rather similar latency distribution between 1.6 and 2.4 ms was found for ipsi- and contralateral EPSPs in SPL and BCC motoneurones, which is compatible with a minimal disynaptic linkage between primary trigeminal afferents and neck motoneurones. Systematic transections of the ipsi- and contralateral trigeminal tracts were performed in the brain stem between 3 and 12 mm rostral to the level of obex. The results demonstrate that both the ipsi- and contralateral disynaptic and late gasserian EPSPs can be mediated via trigeminospinal neurones which take their origin in the nucleus trigeminalis spinalis oralis. Transection of the midline showed that the contralateral trigeminospinal neurones cross in the brain stem. Systematic tracking in and around the ipsilateral trigeminal nuclei demonstrated that the axons of ipsilateral trigeminospinal neurones descend just medial to and/or in the medial part of the nucleus. Spinal cord lesions revealed a location of the axons of the ipsilateral trigeminospinal neurones in the lateral and ventral funiculi. Interaction between the ipsi- and contralateral gasserian EPSPs showed complete summation of the disynaptic EPSP component, while the late components were occluded by about 45%. These results show that the disynaptic EPSPs are mediated by separate trigeminospinal neurones from the ipsi- and contralateral side, while about half of the late EPSPs are mediated by common neurones which receive strong bilateral excitation from commissural neurones in the trigeminal nuclei. Spatial facilitation was found in the late gasserian EPSP but not in the disynaptic gasserian EPSP by conditioning stimulation of cortico- and tectofugal fibres. Disynaptic pyramidal and tectal EPSPs, which are mediated by reticulospinal neurones, were facilitated by a single stimulation in the gasserian ganglion at an optimal interval of 2 ms. It is suggested that primary trigeminal afferents can excite the reticulospinal neurones via a disynaptic trigeminoreticular pathway.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00227964
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    Specific effects of the benzodiazepine midazolam on visual receptive fields in light and dark adapted human subjects (1992)
    Springer
    Psychopharmacology 109 (1992), S. 68-76 
    Details
    ISSN: 1432-2072
    Keywords: Visual system ; Visual receptive fields ; Subthreshold summation ; Shift effect ; Dark adaptation ; Benzodiazepines ; GABA ; Bicuculline ; Dopamine ; Levodopa ; Sulpiride ; Atropine ; Human ; Cat ; Psychophysics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Psychophysical experiments in humans have revealed similar characteristics of visual receptive fields as were found in cats and monkeys from retinal ganglion cell recordings. In addition, in some retinal ganglion cells of cats the GABA antagonist bicuculline decreases the activity of the inhibitory surround. These findings led to two predicitions: 1) benzodiazepines will selectively increase the inhibitory surround of human visual receptive fields, 2) after dark adaptation, no free GABA will be available in the synapses and benzodiazepines will have no effect on the visual system. Characteristics of human receptive fields were determined by subthreshold summation: the contrast threshold of a vertical line was measured dependent on the distance of two parallel flanking lines whose contrast was below threshold. Both hypotheses were confirmed: the threshold in the inhibitory region of receptive fields was specifically increased in a dose-dependent manner by midazolam PO (7.5 mg:P〈0.05; 15 mg:P〈0.01). In dark-adapted subjects no effect of midazolam was found. Control experiments with atropine (1 mg IV), sulpiride (100 mg IM), and levodopa (100 mg PO) showed no specific effect. The visual system may be a model to bridge the gap between animal and human psychopharmacology.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02245482
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    Comparaison des propriétés mécaniques d'une nouvelle xénogreffe osseuse à celles de l'os trabéculaire humain et de Bovin (1992)
    Springer
    European journal of orthopaedic surgery & traumatology 2 (1992), S. 265-268 
    Details
    ISSN: 1432-1068
    Keywords: Bone ; Xenograft ; Young's modulus ; Biomechanics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary The aim of the present study was to compare the mechanical properties of two types of a new bone xenograft, T650 (Luddoc®) (Dense and Medium) with human and fresh bovine trabecular bone. Compressive testing was performed to destruction with a constant deformation rate of 0,025 mm min−1. Shear destructive testing was also carried out. Under our experimental conditions, Young's modulus of dense T650 (132.9 ± 52.3 MPa) do not differ significantly from that of fresh bovine bone (117.5 ± 61.5 MPa); and that of medium T650 (79.92 ± 37.3 MPa) did not differ significantly from human bone (77,36 ± 54,9 MPa). The shear force is required to destroy dense T650 (494 ± 167 N) did not differ significantly from those for fresh bovine bone (558 ± 104 N). Whereas the values for medium T650 were significantly lower (359 ± 155 N). The stress-strain curves obtained from all the specimens did not differ significantly. The process used to obtain T650 did not modify the mechanical properties of bovine trabecular bone.
    Notes: Résumé Le but de ce travail est de comparer les propriétés mécaniques d'une nouvelle xénogreffe osseuse le T650 (Luddoc®) répartie en deux sous groupes dits “dense” et “moyen” à celle de l'os trabéculaire humain et de bovin. Des tests de compression avec un rapport de déformation constant de 0,025 mm min−1 et des tests de rupture au cisaillement sont appliqués. Dans les conditions expérimentales utilisées, le module de Young du T650 dense (132,9 ± 52,3 MPa) est comparable à celui de l'os trabéculaire frais de bovin (117,5 ± 61,5 MPa), celui du T650 moyen (79,92 ± 37,3 MPa) à celui de l'os humain (77,36 ± 54,9 MPa). La résistance à la rupture au cisaillement du T650 dense (494 ± 167 N) est comparable à celle de l'os trabéculaire de veau frais (558 ± 104 N). Les valeurs du T650 moyen sont significativement plus faibles (359 ± 155 N). Les courbes compression/déformation sont similaires pour les différents types d'éprouvettes testés. Les traitements subis par l'os trabéculaire de veau pour l'obtention du T650 n'affectent pas ses propriétés mécaniques.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01742445
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    Decrease in bone strength of cadmium-treated young and old rats (1992)
    Springer
    Archives of toxicology 66 (1992), S. 315-320 
    Details
    ISSN: 1432-0738
    Keywords: Cadmium ; Rat ; Bone ; Long-term administration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A decrease in mechanical strength of bones was observed both in young and old rats for long periods of administration of cadmium. Young (3-week-old) female rats were given 0 (control), 5 and 10 ppm cadmium in drinking water, respectively, for 20 weeks. Old (18-month old) female rats were given 0 (control) and 40 ppm cadmium in drinking water, respectively, for 7 months. The compression strengths of bones of young rats which were given 10 ppm cadmium, and those of old rats which were given 40 ppm cadmium, significantly decreased at the distal end portion of femur. Cadmium contents in bones in the 10 ppm and 40 ppm groups were about 110 and 210 ng/g dry weight, respectively. The present result confirmed that cadmium has a lesional effect on the mechanical strength of bone at the concentration of 100–200 ng/g in dry weight of bone, for both young and old rats.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01973625
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    Usefulness of an acoustic edge artifact in assessment of the Ilizarov corticotomy interval (1992)
    Springer
    Skeletal radiology 21 (1992), S. 293-296 
    Details
    ISSN: 1432-2161
    Keywords: Ultrasound ; Bone ; Ilizarov ; Artifact ; Measurement
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Thirty-three ultrasound examinations of the corticotomy interval of patients undergoing Ilizarov procedures were retrospectively evaluated for the presence or absence of an acoustic edge artifact. This artifact, consisting of a fine anechoic band, has been previously described in phantom models and is presumed to be due to phase cancellation effects. We demonstrated this artifact in 8 of 33 examinations. The artifact proved helpful in identifying the location of the corticotomy margin, even when this margin was obscured by the presence of developing periosteal new bone. Attention to technical factors is, however, important. We believe that this artifact may have a useful role in the routine monitoring of the Ilizarov patient.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00241766
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  • 61
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    Immuno-electron-microscopic localization of laminin and collagen type IV in normal and denervated tooth pulp of the cat (1992)
    Springer
    Cell & tissue research 270 (1992), S. 157-164 
    Details
    ISSN: 1432-0878
    Keywords: Dental pulp ; Laminin ; Collagen IV ; Odontoblast ; Nerve regeneration ; Immunocytochemistry ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The distribution of laminin-like immunoreactivity in adult normal and denervated cat mandibular tooth pulps was studied by the use of fluorescence microscopy and pre-embedding immunogold electron microscopy. Immunoreactivity to collagen IV was also assessed in order to distinguish basement membranes. In normal pulps, light-microscope laminin-like immunoreactivity was strong along blood vessels and Schwann cell sheaths, and a faint immunoreactivity was seen also in the odontoblast layer. Electron microscopy confirmed the laminin-like immunoreactivity of endothelial and Schwann cell basement membranes at all pulpal levels. In the odontoblast layer and the predentine, nerve-like structures lacking basement membranes but possessing strong membrane laminin-like immunoreactivity were encountered. In addition, a clear-cut laminin-like immunoreactivity of plasma membranes of the somata and processes of odontoblasts was seen. Observations on denervated pulps as well as pulps in which nerve regeneration had taken place did not reveal any changes in the pattern of laminin-immunoreactivity in basement membranes or odontoblasts. Distribution of collagen IV-like immunoreactivity was very similar to laminin-like immunoreactivity in basement membranes of blood vessels and Schwann cells, and appeared unaffected by denervation. The odontoblasts and nerve-like profiles in the odontoblast layer were devoid of collagen IV-like immunoreactivity. We propose that odontoblast-associated laminin could be of significance as guidance for regenerating terminal pulpal nerve fibers to appropriate targets.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00381890
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    Expression of mRNA of parathyroid hormone-related peptide in fetal bones of the rat (1992)
    Springer
    Cell & tissue research 270 (1992), S. 597-600 
    Details
    ISSN: 1432-0878
    Keywords: Parathyroid hormone-related peptide ; Osteocalcin-mRNA ; In situ hybridization histochemistry ; Bone ; Rat (Wistar)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Previous studies have indicated that 19-dayold fetal long bones of the rat contain an adenylyl cyclase-stimulating activity antigenically related to parathyroid hormone-related peptide. To ascertain its origin, Northern blotting and in situ hybridization histochemistry were performed. Results demonstrate that mRNA of parathyroid hormone-related peptide is present in RNA extracted from fetal long bones of the rat and that cells responsible for its production are localized in the periosteum. These cells are not mature osteoblasts because they do not synthesize mRNA of osteocalcin. Thus the present study shows that parathyroid hormone-related peptide could be produced locally, at least in part, in the skeleton of fetal rats.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00645063
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  • 63
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    Light-and electron-microscopic studies of the somatostatin-immunoreactive plexus in the cat retina (1992)
    Springer
    Cell & tissue research 267 (1992), S. 57-66 
    Details
    ISSN: 1432-0878
    Keywords: Retina ; Somatostatin immunoreactivity ; Amacrine cells ; Synapses ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Two monoclonal antibodies directed against somatostatin 14 were used to study immunoreactive neurons, their processes and their synapses in the cat retina. In retinal whole-mounts, a sparse population of wide-field displaced amacrine cells was observed predominantly in the ventral retina and near the retinal margin. Processes of these cells ramified mainly in two distinct strata within the inner plexiform layer: one near the inner nuclear layer (INL), and the other near the ganglion cell layer (GCL). The length of immunoreactive fibres within each plexus was measured: 232±32 mm/mm2 near the INL and 230±74 mm/mm2 near the GCL in all retinal regions. The immunoreactive processes were studied using electron-microscopic techniques; conventional and some ribbon-containing synapses (“dyads”) were found. Immunolabelled processes received input synapses from other amacrine cell processes. These investigations provide further evidence that this cell population has a diffuse, regulatory or modulatory role for visual-information processing in the inner plexiform layer.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00318691
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    Is pelvic bone mineral content assessed through dual energy X-ray absorptionmetry an appropriate anatomical area for bone mass estimation in women? (1992)
    Springer
    Clinical rheumatology 11 (1992), S. 508-511 
    Details
    ISSN: 1434-9949
    Keywords: Total ; Body ; Bone ; Mineral ; Content ; Pelvic ; Bone ; Mineral ; Content ; Postmenopausal ; Osteoporosis ; Bone ; Mass
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Bibliographic references seem very controversill regarding the most appropriate anatomical area for bone mass estimation. Since some overlapping in the different bone mass measurements among normal and osteoporotic females has been observed, we have studied the bone mineral content of the pelvic bone through DEXA, and have correlated it with the total body bone mineral content, a highly discriminating measure, in order to observe whether pelvic bone mineral may be a useful measure in bone mass assessment. Pelvic and total body bone mineral values did not decrease until menopause in 104 normal premenopausal females aged 20 to 49 years. On the other hand, these values decreased in normal postmenopausal women (n=44) aged 50 to 65 years (p〈0.001), with a 16% pelvic bone mineral content and an 11% total body bone mineral content decrease. Osteoporotic females (n=30), showed lower values for both levels than normal postmenopausal ones (p〈0.001), with a 54% pelvic and a 24% total decrease. A 15% overlap was observed when pelvic values between normal postmenopausal and osteoporotic females were compared. The greater percentage decrease in pelvic BMC compared to total body bone mineral content and the lower overlap observed suggest that the pelvis may be an ideal anatomical area for bone mass evaluations.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02283108
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    Conformational analysis of a 12-residue analogue of mastoparan and of mastoparan X (1992)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 12 (1992), S. 111-116 
    Details
    ISSN: 0887-3585
    Keywords: protein folding ; multiple minima problem ; peptide conformation ; energy calculation ; helices ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: We have investigated the conformational properties of a truncated analogue of mastoparan and of mastoparan X, both peptides from wasp venom. The electrostatically driven Monte Carlo method was used to explore the conformational space of these short peptides. The initial conformations used in this study, mainly random ones, led to α-helical conformations. The α-helical conformations thus found exhibit an amphipathic character. These results are in accord with experimental data from NMR and CD spectroscopy.
    Additional Material: 1 Ill.
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    URL: http://dx.doi.org/10.1002/prot.340120204
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    Masthead (1992)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 12 (1992) 
    Details
    ISSN: 0887-3585
    Keywords: Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/prot.340120401
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  • 67
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    Helix packing of leucine-rich peptides: A parallel leucine ladder in the structure of Boc-Aib-Leu-Aib-Aib-Leu-Leu-Leu-Aib-Leu-Aib-OMe (1992)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 12 (1992), S. 324-330 
    Details
    ISSN: 0887-3585
    Keywords: X-ray diffraction analysis ; hydrogen bonds ; peptide conformation ; 310/α-helix transition ; antiparallel helix packing ; leucyl-leucyl interaction ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: The packing of peptide helices in crystals of the leucine-rich decapeptide Boc-Aib-Leu-Aib-Aib-Leu-Leu-Leu-Aib-Leu-Aib-OMe provides an example of ladder-like leucylleucyl interactions between neighboring molecules. The peptide molecule forms a helix with five 5→1 hydrogen bonds and two 4→1 hydrogen bonds near the C terminus. Three head-to-tail NH ċ O = C hydrogen bonds between helices form continuous columns of helices in the crystal. The helicial columns associate in an antiparallel fashion, except for the association of Leu ċ Leu side chains, which occurs along the diagonal of the cell where the peptide helices are parallel. The peptide, with formula C56H102N10O13, crystallizes in space group P212121 with Z = 4 and cell parameters a = 16.774(3) Å, b = 20.032(3) Å and c = 20.117(3) Å; overall agreement factor R = 10.7% for 2014 data with |Fobs| 〈 3σ(F); resolution 1.0 Å.
    Additional Material: 4 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/prot.340120404
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  • 68
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    Protease pro region required for folding is a potent inhibitor of the mature enzyme (1992)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 12 (1992), S. 339-344 
    Details
    ISSN: 0887-3585
    Keywords: protein folding ; pro region ; protease inhibition ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: α-Lytic protease, an extracellular bacterial serine protease, is synthesized with a large pro region that is required in vivo for the proper folding of the protease domain. To allow detailed mechanistic study, we have reconstituted pro region-dependent folding in vitro. The pro region promotes folding of the protease domain in the absence of other protein factors or exogenous energy sources. Surprisingly, we find that the pro region is a high affinity inhibitor of the mature protease. The pro region also inhibits the closely related Streptomyces griseus protease B, but not the more distantly related, yet structurally similar protease, elastase. Based on these data, we suggest a mechanism in which pro region binding reduces the free energy of a late folding transition state having native-like structure.
    Additional Material: 3 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/prot.340120406
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    Masthead (1992)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 13 (1992) 
    Details
    ISSN: 0887-3585
    Keywords: Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/prot.340130101
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    The high-resolution crystal structure of porcine pepsinogen (1992)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 13 (1992), S. 1-25 
    Details
    ISSN: 0887-3585
    Keywords: aspartic proteinase zymogen ; molecular replacement ; structure-function ; activation peptide ; acid activation ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: The structure of porcine pepsinogen at pH 6.1 has been refined to an R-factor of 0.173 for data extending to 1.65 Å. The final model contains 180 solvent molecules and lacks density for residues 157-161. The structure of this aspartic proteinase zymogen possesses many of the characteristics of pepsin, the mature enzyme. The secondary structure of the zymogen consists predominantly of β-sheet, with an approximate 2-fold axis of symmetry. The activation peptide packs into the active site cleft, and the N-terminus (IP-9P) occupies the position of the mature N-terminus (1-9). Thus changes upon activation include excision of the activation peptide and proper relocation of the mature N-terminus. The activation peptide or residues of the displaced mature N-terminus make specific interactions with the substrate binding subsites. The active site of pepsinogen is intact; thus the lack of activity of pepsinogen is not due to a deformation of the active site. Nine ion pairs in pepsinogen may be important in the advent of activation and involve the activation peptide or regions of the mature N-terminus which are relocated in the mature enzyme. The activation peptide-pepsin junction, 44P-1, is characterized by high thermal parameters and weak density, indicating a flexible structure which would be accessible to cleavage. Pepsinogen is an appropriate model for the structures of other zymogens in the aspartic proteinase family. © 1992 Wiley-Liss, Inc.
    Additional Material: 17 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/prot.340130102
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  • 71
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    Masthead (1992)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 13 (1992) 
    Details
    ISSN: 0887-3585
    Keywords: Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/prot.340130201
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  • 72
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    Molecular modeling of an antigenic complex between a viral peptide and a class I major histocompatibility glycoprotein (1992)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 13 (1992), S. 70-85 
    Details
    ISSN: 0887-3585
    Keywords: major histocompatibility complex ; antigenic peptide ; molecular dynamics ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Computer simulation of the conformations of short antigenic peptides (5-10 residues) either free or bound to their receptor, the major histocompatibility complex (MHC)-encoded glycoprotein H-2 Ld, was employed to explain experimentally determined differences in the antigenic activities within a set of related peptides. Starting for each sequence from the most probable conformations disclosed by a pattern-recognition technique, several energy-minimized structures were subjected to molecular dynamics simulations (MD) either in vacuo or solvated by water molecules. Notably, antigenic potencies were found to correlate to the peptides propensity to form and maintain an overall α-helical conformation through regular i,i+4 hydrogen bonds. Accordingly, less active or inactive peptides showed a strong tendency to form i,i+3 hydrogen bonds at their N-terminal end. Experimental data documented that the C-terminal residue is critical for interaction of the peptide with H-2 Ld. This finding could be satisfactorily explained by a 3-D Q.S.A.R. analysis postulating interactions between ligand and receptor by hydrophobic forces. A 3-D model is proposed for the complex between a high-affinity nonapeptide and the H-2 Ld receptor. First, the H-2 Ld molecule was built from X-ray coordinates of two homologous proteins: HLA-A2 and HLA-Aw68, energy-minimized and studied by MD simulations. With HLA-A2 as template, the only realistic simulation was achieved for a solvated model with minor deviations of the MD mean structure from the X-ray conformation. Water simulation of the H-2 Ld protein in complex with the antigenic nonapeptide was then achieved with the template-derived optimal parameters. The bound peptide retains mainly its α-helical conformation and binds to hydrophobic residues of H-2 Ld that correspond to highly polymorphic positions of MHC proteins. The orientation of the nonapeptide in the binding cleft is in accordance with the experimentally determined distribution of its MHC receptor-binding residues (agretope residues). Thus, computer simulation was successfully employed to explain functional data and predicts α-helical conformation for the bound peptide. © 1992 Wiley-Liss, Inc.
    Additional Material: 13 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/prot.340130107
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    Characterization of HIV-1 p24 self-association using analytical affinity chromatography (1992)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 13 (1992), S. 112-119 
    Details
    ISSN: 0887-3585
    Keywords: analytical affinty chromatography ; self-association ; HIV p24gag ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Analytical affinity chromatography (AAC) was used to detect and quantitate the self-association of p24gag, the major structural capsid protein of human immunodeficiency virus (HIV-1). p24gag was immobilized on a hydrophilic polymer (methacrylate) chromatographic support. The resulting affinity column was able to interact with soluble p24, as judged by the chromatographic retardation of the soluble protein upon isocratic elution undernonchaotropic binding conditions. The variation of elution volume with soluble protein concentration fit to a monomer-dimer model for self-association. The soluble p24-immobilized p24 association process was observed using both frontal and zonal elution AAC at varying pH values; the dissociation constant was 3-4 × 10-5 M at pH 7. That p24 monomer associates to dimers was determined in solution using analytical ultracentrifugation. The solution Kd was 1.3 × 10-5 M at pH 7. AAC in the zonal elution mode provides a simple and rapid means to screen for other HIV-1 macromolecules that may interact with p24 as well as for modulators, including antagonists, of HIV p24 protein assembly. © 1992 Wiley-Liss, Inc.
    Additional Material: 5 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/prot.340130204
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    Structural and energetic differences between insertions and substitutions in staphylococcal nuclease (1992)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 13 (1992), S. 132-140 
    Details
    ISSN: 0887-3585
    Keywords: protein stability ; insertion mutations ; substitution mutations ; guanidine hydrochloride denaturation ; conformational changes ; circular dichroism spectroscopy ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: In a previous study, the small protein staphylococcal nuclease was shown to readily accommodate single alanine and glycine insertions, with average losses in stability comparable to substitutions at the same sites (PROT. 7:29-305, 1990). To more fully explore this unexpected adaptability to changes in residue spacing, 2 double amino acid insertions (alanyl-glycine, glycyl-glycine) and 3 additional single amino acid insertions with dissimilar side chains (proline, leucine, and glutamine) were constructed at 10 of the sites previously studied. At 8 of these sites, the type of amino acid side chain on the inserted residue significantly influenced the stability of the mutant protein. However, at 9 of the 10 sites, the double insertions were found to be no more destabilizing than the single alanine or glycine insertions. In contrast, double substitution mutations of staphylococcal nuclease, which replace two adjacent residues with alanine, do not show this striking degree of non-additivity. A comparison of the effects of single glutamine and single glycine insertions with alanyl-glycine insertions indicates that insertion of alanine into the peptide backbone is, on average, less destabilizing than appending the equivalent atoms onto the side chain of a glycine insertion. To explain their very different energetic effects, we propose that, unlike most substitutions, the inserted residue(s) must induce lateral displacements of the polypeptide chain, forcing the folded conformation away from that of wild type. The resulting obligatory shifts in the positioning of residues flanking the insertion generate a large number of degrees of freedom around which the mutant structure can relax. From the many alternative packing and bonding arrangements thus made available to the polypeptide chain, the energetically most favorable is selected. © 1992 Wiley-Liss, Inc.
    Additional Material: 3 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/prot.340130206
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    Fast and simple monte carlo algorithm for side chain optimization in proteins: Application to model building by homology (1992)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 14 (1992), S. 213-223 
    Details
    ISSN: 0887-3585
    Keywords: protein folding ; protein structure ; rotamers ; simulated annealing ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: An unknown protein structure can be predicted with fair accuracy once an evolutionary connection at the sequence level has been made to a protein of known 3-D structure. In model building by homology, one typically starts with a backbone framework, rebuilds new loop regions, and replaces nonconserved side chains. Here, we use an extremely efficient Monte Carlo algorithm in rotamer space with simulated annealing and simple potential energy functions to optimize the packing of side chains on given backbone models. Optimized models are generated within minutes on a workstation, with reasonable accuracy (average of 81% side chain χ1 dihedral angles correct in the cores of proteins determined at better than 2.5 Å resolution). As expected, the quality of the models decreases with decreasing accuracy of backbone coordinates. If the backbone was taken from a homologous rather than the same protein, about 70% side chain X1 angles were modeled correctly in the core in a case of strong homology and about 60% in a case of medium homology. The algorithm can be used in automated, fast, and reproducible model building by homology. © 1992 Wiley-Liss, Inc.
    Additional Material: 6 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/prot.340140208
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    Protein design on computers. Five new proteins: Shpilka, grendel, fingerclasp, leather, and aida (1992)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 12 (1992), S. 105-110 
    Details
    ISSN: 0887-3585
    Keywords: protein structure ; protein sequences ; protein design de novo ; protein engineering ; computer algorithms ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: What is the current state of the art in protein design? This question was approached in a recent two-week protein design workshop sponsored by EMBO and held at the EMBL in Heidelberg. The goals were to test available design tools and to explore new design strategies. Five novel proteins were designed: Shpilka, a sandwich of two four-stranded β-sheets, a scaffold on which to explore variations in loop topology; Grendel, a four-helical membrane anchor, ready for fusion to water-soluble functional domains; Fingerclasp, a dimer of interdigitating β-β-α units, the simplest variant of the “handshake” structural class; Aida, an antibody binding surface intended to be specific for flavodoxin; Leather - a minimal NAD binding domain, extracted from a larger protein. Each design is available as a set of three-dimensional coordinates, the corresponding amino acid sequence and a set of analytical results. The designs are placed in the public domain for scrutiny, improvement, and possible experimental verification.
    Additional Material: 2 Ill.
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    URL: http://dx.doi.org/10.1002/prot.340120203
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    Correlations of atomic movements in lysozyme crystals (1992)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 12 (1992), S. 145-157 
    Details
    ISSN: 0887-3585
    Keywords: thermal diffuse X-ray scattering ; protein disorder ; molecular dynamics ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Diffuse scattering data have been collected on two crystal forms of lysozyme, tetragonal and triclinic, using synchrotron radiation. The observed diffraction patterns were simulated using an exact theory for simple model crystals which relates the diffuse scattering intensity distribution to the amplitudes and correlations of atomic movements. Although the mean square displacements in the tetragonal form are twice that in the triclinic crystal, the predominent component of atomic movement in both crystals is accounted for by short-range coupled motions where displacement correlations decay exponentially as a function of atomic separation, with a relaxation distance of ≈ 6 Å. Lattice coupled movements with a correlation distance ≈ 50 Å account for only about 5-10% of the total atomic mean square displacements in the protein crystals. The results contradict various presumptions that the disorder in protein crystals can be modeled predominantly by elastic vibrations or rigid body movements.
    Additional Material: 3 Ill.
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    URL: http://dx.doi.org/10.1002/prot.340120208
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    Integrity of refolded and reoxidized gelatin-binding fragments of fibronectin (1992)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 12 (1992), S. 180-187 
    Details
    ISSN: 0887-3585
    Keywords: fibronectin ; domain ; collagen ; folding ; disulfide ; fluorescence ; GdmCl ; renaturation ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: The gelatin-binding region of fibronectin is easily isolated as a stable and functional 42-kDa fragment (42-kDa GBF) containing four type I “finger” modules and two type II “kringle-like” modules arranged in the order I6-II1-II2-I7-I8-I9, where the numbers designate the order of these modules in each of the two polypeptide chains. Each module forms an independently folded domain stabilized by two disulfide bonds. Reduction of disulfides caused large changes in the intrinsic fluorescence and abolished the gelatin-binding activity of 42-kDa GBF and two nonoverlapping gelatin-binding subfragments, 30-kDa GBF (I6-II1-II2-I7) and 21-kDa GBF (I8-I9). However, high yields of active material could be regenerated, without diluting the protein, by dialysis into GdmCl followed by slow overnight removal of GdmCl while maintaining the redox potential with a mixture of oxidized and reduced glutathione. Fluorescence spectroscopic analysis indicated that the tertiary structure and thermodynamic stability of the refolded fragments were similar to those of the originals. The refolded fragments were quantitatively indistinguishable from the originals with respect to their dissociation constants for binding to a fluorescent-labeled collagen fragment. The results suggest that all or most of the cystines, a total of 24 in 42-kDa GBF, are correctly paired in the refolded products and that the tertiary structure was completely recovered. The fact that the 30- and 21-kDa fragments bind with a similar affinity proves the existence of at least two nonoverlapping sites in 42-kDa GBF that recognize gelatin.
    Additional Material: 7 Ill.
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    URL: http://dx.doi.org/10.1002/prot.340120211
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    Comparison of the hemocyanin β-barrel with other greek key β-barrels: Possible importance of the “β-zipper” in protein structure and folding (1992)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 12 (1992), S. 278-298 
    Details
    ISSN: 0887-3585
    Keywords: folding nucleation ; hydrophobic cluster ; conserved loop length ; structure-sequence relationship ; sequence patterns ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: The Greek key β-barrel topology is a folding motif observed in many proteins of widespread evolutionary origin. The arthropodan hemocyanins also have such a Greek key β-barrel, which forms the core of the third domain of this protein. The hemocyanin β-barrel was found to be structurally very similar to the β-barrels of the immunoglobulin domains, Cu,Zn-superoxide dismutase and the chromophore carrying antitumor proteins. The structural similarity within this group of protein families is not accompanied by an evolutionary or functional relationship. It is therefore possible to study structure-sequence relations without bias from nonstructural constraints. The present study reports a conserved pattern of features in these Greek key β-barrels that is strongly suggestive of a folding nucleation site. This proposed nucleation site, which we call a “β-zipper,” shows a pattern of well-conserved, large hydrophobic residues on two sequential β-strands joined by a short loop. Each β-zipper strand is near the center of one of the β-sheets, so that the two strands face each other from opposite sides of the barrel and interact through their hydrophobic side chains, rather than forming a hydrogen-bonded β-hairpin. Other protein families with Greek key β-barrels that do not as strongly resemble the immunoglobulin fold - such as the azurins, plastocyanins, crystallins, and prealbumins - also contain the β-zipper pattern, which might therefore be a universal feature of Greek key β-barrel proteins.
    Additional Material: 9 Ill.
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    URL: http://dx.doi.org/10.1002/prot.340120306
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    Analysis of protein sheet topologies by graph theoretical methods (1992)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 12 (1992), S. 314-323 
    Details
    ISSN: 0887-3585
    Keywords: structure analysis ; graph theory ; protein structure ; β sheet ; retrieval ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: In order to find rules for the secondary structure prediction of proteins which describe the (sequentially) long-range interactions in sheet structures methods of applied graph theory were used. The so called β graph which describes the sheet topology was defined for every protein in the Brookhaven Data Bank containing β sheets. The resemblance of proteins at that topological level is discussed, and four notations and graphic representations of sheets which describe the sequential and topological neighborhoods of the strands were derived. This description level supports the usage of data structures which allow the implementation of efficient algorithms for the analysis and comparison of β structures in proteins. A computer program for the representation and retrieval of bibliographic data and β sheet structures was implemented. Some examples for substructure search illustrate the usefulness of the program. Two graphic catalogues were compiled: one contains all β graphs of PDB proteins and the other all occurring different greek key descriptions.
    Additional Material: 8 Ill.
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    URL: http://dx.doi.org/10.1002/prot.340120403
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    Stereochemical quality of protein structure coordinates (1992)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 12 (1992), S. 345-364 
    Details
    ISSN: 0887-3585
    Keywords: protein structure ; crystallography ; errors ; φ,ψ distribution ; χ1 angles ; stereochemical parameters ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Methods have been developed to assess the stereochemical quality of any protein structure both globally and locally using various criteria. Several parameters can be derived from the coordinates of a given structure. Global parameters include the distribution of φ,ψ and χ1 torsion angles, and hydrogen bond energies. There are clear correlations between these parameters and resolution; as the resolution improves, the distribution of the parameters becomes more clustered. These features show a broad distribution about ideal values derived from high-resolution structures. Some structures have tightly clustered distributions even at relatively low resolutions, while others show abnormal scatter though the data go to high resolution. Additional indicators of local irregularity include proline φ angles, peptide bond planarities, disulfide bond lengths, and their χ3 torsion angles. These stereochemical parameters have been used to generate measures of stereochemical quality which provide a simple guide as to the reliability of a structure, in addition to the most important measures, resolution and R-factor. The parameters used in this evaluation are not novel, and are easily calculated from structure coordinates. A program suite is currently being developed which will quickly check a given structure, highlighting unusual stereochemistry and possible errors.
    Additional Material: 17 Ill.
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    URL: http://dx.doi.org/10.1002/prot.340120407
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    Use of conditional probabilities for determining relationships between amino acid sequence and protein secondary structure (1992)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 12 (1992), S. 382-399 
    Details
    ISSN: 0887-3585
    Keywords: protein secondary structure ; amino acid sequence ; distributions ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: The conditional probability, P(σ|x), is a statement of the probability that the value of σ will be found given the prior information that a value of x has been observed. Here σ represents any one of the secondary structure types, α, β, τ, and ρ for helix, sheet, turn, and random, respectively, and x represents a sequence attribute, including, but not limited to: (1) hydropathy; (2) hydrophobic moments assuming helix and sheet; (3) Richardson and Richardson helical N-cap and C-cap values; (4) Chou-Fasman conformational parameters for helix, Pα, for sheet, Pβ, and for turn, Pτ; and (5) Garnier, Osguthorpe, and Robson (GOR) information values for helix, Iα, for sheet, Iβ, for turn, I,τ, and for random structure, Iρ.Plots of P (σ|x) vs. x are demonstrated to provide information about the correlation between structure and attribute, σ and x. The separations between different P (σ|x) vs. x curves indicate the capacity of a given attribute to discriminate between different secondary structural types and permit comparison of different attributes. P (α|x), P (β|x), P (τ|x) and P (ρ|x) vs. x plots show that the most useful attributes for discriminating helix are, in order: hydrophobic moment assuming helix 〉 Pα » N-cap 〉 C-cap ≈ Iα ≈ Iτ. The information value for turns, Iτ, was found to discriminate helix better than turns. Discrimination for sheet was found to be in the following order: Iβ » Pβ ≈ hydropathy 〉 Iρ ≈ hydrophobic moment assuming sheet.Three attributes, at their low values, were found to give significant discrimination for the absence of helix: Iα ≈ Pα ≈ hydrophobic moment assuming helix. Also, three other attributes were found to indicate the absence of sheet: Pβ » Iτ ≈ hydropathy. Indications of the absence of σ could be as useful for some applications as the indication of the presence of σ.
    Additional Material: 7 Ill.
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    URL: http://dx.doi.org/10.1002/prot.340120410
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    Substrate mobility in a deeply buried active site: Analysis of norcamphor bound to cytochrome P-450cam as determined by a 201-psec molecular dynamics simulation (1992)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 13 (1992), S. 26-37 
    Details
    ISSN: 0887-3585
    Keywords: norcamphor ; P450CIA1 ; substrate specificity ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: While cytochrome P-450cam, catalyzes the hydroxylation of camphor to 5-exo-hydroxycamphor with 100% stereospecificity, norcamphor is hydroxylated by this enzyme yielding 45% 5-exo-, 47% 6-exo-, and 8% 3-exo-hydroxynorcamphor (Atkins, W.M., Sligar, S.G., J. Am. Chem. Soc. 109:3754-3760, 1987). The present study describes a 201-psec molecular dynamics (MD) simulation of norcamphorbound cytochrome P-450cam to elucidate the relationship between substrate conformational mobility and formation of alternative products. First, these data suggest that the product specificity is, at least partially, due to the mobility of the substrate within the active site. Second, the high mobility of norcamphor in the active site leads to an average increase in separation between the home iron and the substrate of about 1.0 Å; this increase in separation may be the cause of the uncoupling of electron transfer when norcamphor is the substrate. Third, the active site water located in the norcamphor-bound crystal structure possesses mobility that correlates well with the spin-state equilibrium of this enzyme-substrate complex. © 1992 Wiley-Liss, Inc.
    Additional Material: 11 Ill.
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    URL: http://dx.doi.org/10.1002/prot.340130103
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    Deconvolution of the circular dichroism spectra of proteins: The circular dichroism spectra of the antiparallel β-sheet in proteins (1992)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 13 (1992), S. 57-69 
    Details
    ISSN: 0887-3585
    Keywords: protein conformation ; aromatic contribution ; disulfide contribution ; CD spectra of the main secondary structural elements in proteins ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: A recently developed algorithm, called Convex Constraint Analysis (CCA), was successfully applied to determine the circular dichroism (CD) spectra of the pure β-pleated sheet in globular proteins. On the basis of X-ray diffraction determined secondary structures, the original data set used (Perczel, A., Hollosi, M., Tusnady, G. Fasman, G.D. Convex constraint analysis: A natural deconvolution of circular dichroism curves of proteins, Prot. Eng., 4:-669-679, 1991), was improved by the addition of proteins with high β-pleated sheet content. The analysis yielded CD curves of the pure components of the main secondary structural elements (α-helix, antiparallel β-pleated sheet, β-turns, and unordered conformation), as well as a curve attributed to the “aromatic contribution” in the wavelength range of 195-240 nm. Upon deconvolution the curves obtained were assigned to various secondary structures. The calculated weights (percentages determining the contributions of each pure component curve in the measured CD spectra of a given protein) were correlated with the X-ray diffraction determined percentages in an assignment procedure and were evaluated. The Pearson product correlation coefficients (R) are significant for all five components. The new pure component curves, which were obtained through deconvolution of the protein CD spectra alone, are promising candidates for determining the percentages of the secondary structural components in globular proteins without the necessity of adopting an X-ray database. The CD spectrum of the CheY protein was interesting because it has the characteristic shape associated with the α-helical structure, but upon analysis yielded a considerable amount of β-sheet in agreement with the X-ray structure. © 1992 Wiley-Liss, Inc.
    Additional Material: 8 Ill.
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    URL: http://dx.doi.org/10.1002/prot.340130106
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    Continuum electrostatics of the C-peptide: Anatomy of the problem (1992)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 13 (1992), S. 120-131 
    Details
    ISSN: 0887-3585
    Keywords: protein folding ; α-helix ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: A computational study of the role of all ionizable groups of the C-peptide in its helix-coil transition is performed within the framework of continuum electrostatics. The method employed in our computations involves a numeric solution of the Poisson equation with the Boundary Element Method. Our calculations correctly predict the experimentally observed trends in the helix-coil equilibrium of the C-peptide, and suggest that the mechanisms involved are more complex than usually presumed in the literature. Our results suggest that electrostatic interactions in the unfolded conformation are often more important than in the helix, total electrostatic contribution to the helix-coil transition due to the side chains of the C-peptide destabilizes the helix, changes in the helix stability produced by the changes in the ionization state of the side chains are dominated by side chain effects, the effect of the helix dipole on the energetics of the helix-coil transition of the C-peptide is either minor or similar to other contributions in magnitude; while the formation of a salt bridge is electrostatically favorable, formation of the hydrogen bond between a charged and a polar side chains is not. Factors limiting the accuracy of the computations are discussed. © 1992 Wiley-Liss, Inc.
    Additional Material: 1 Ill.
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    URL: http://dx.doi.org/10.1002/prot.340130205
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    Crystallization and preliminary X-ray diffraction analysis of staphylococcal enterotoxin type C (1992)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 13 (1992), S. 152-157 
    Details
    ISSN: 0887-3585
    Keywords: Staphylococcus aureus ; bacterial toxins ; structure-function ; protein structure ; crystallography ; pyrogenic toxins ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: The Type C staphylococcal enterotoxin produced by Staphylococcus aureus strain FRI-909 has been crystallized using a combination of two precipitants, ammonium sulfate and polyethylene glycol 400, with the addition of small amounts of detergent. Two related crystal forms have been obtained, one triclinic, and one tetragonal, both with one toxin molecule per asymmetric unit. These crystals are stable for at least 75 hr in the X-ray beam and diffract to at least 2.2 and 2.6 Å, respectively. The triclinic crystals have unit cell parameters a = 38.5 Å, b = 43.7 Å, c = 36.9 Å, and interaxial angles α = 99.9°, β = 95.8°, and γ = 98.5°. The tetragonal crystals are of space group P4122 with unit cell parameters a = 43.4 Å and c = 278.0 Å. © 1992 Wiley-Liss, Inc.
    Additional Material: 4 Ill.
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    URL: http://dx.doi.org/10.1002/prot.340130208
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    Detection of local structures in reduced unfolded bovine pancreatic trypsin inhibitor (1992)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 13 (1992), S. 162-173 
    Details
    ISSN: 0887-3585
    Keywords: protein folding ; folding intermediates ; time resolved fluorescence ; nonradiative excitation energy transfer ; BPTI ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: The structure of BPTI and reduced BPTI in concentrated guanidinium HCI (GUHCl) in the presence of glycerol has been probed by measurements of dynamic nonradiative excitation energy transfer between probes attached to its amino groups. Inter probe distance distributions were obtained from analysis of donor fluorescence decay curves and used to characterize local structures in unordered states of the protein. Site specifically fluorescently labeled BPTI derivatives (1-n)BPTI (n = 15, 20, 41, 46) were used, each carrying a 2-methoxy-naphthyl-1-methylenyl group (MNA) at the N-terminal amino group of arg1 and 7-(dimethylamino)-coumarin-4-yl-acetyl residue (DA-coum) at one of its ε-NH2 groups of the lysine side chains. Analysis of donor fluorescence decay kinetics gave the interprobe distance distributions in the native and denatured states.The N-terminal-segment, residues 1-15, is in an extended conformation (with an average interprobe distance of 34 ± 2 Å) in the native state. Upon unfolding by reduction with DTT or β-mercapto ethanol in 6 M GUHCl/glycerol mixture, the conformation of this segment relaxed to a state characterized by a reduced averageinterprobe distance and a larger width of the distances distribution. The average distance between residues 1 and 26, i.e., between the N-terminus and the turn of the twisted β sheet element (residues 18-35), increased upon unfolding. At -30°C in the above solvent, the distribution between these two sites was probably composed of two conformational subpopulations. About 45 ±20% of the molecules were characterized by a short interprobe distance (like the native state) representing a compact conformation, and 55 ± 20% of the molecules showed large interprobe distances representing an expanded (unfolded) conformation.Thus local structures seem to exist in reduced denatured BPTI even underdenaturing conditions in 6 M GUHCl/glycerol mixtures. Some of those structures are unstable in guanidinium isothiocyanate (GUSCN). The method introduced here is suitable for probing local structures and very long range interactions in unfolded folded proteins and for search for folding initiation sites (FISs) and early folding intermediates. © 1992 Wiley-Liss, Inc.
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    URL: http://dx.doi.org/10.1002/prot.340130210
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    A multiple-start Monte Carlo docking method (1992)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 13 (1992), S. 206-222 
    Details
    ISSN: 0887-3585
    Keywords: molecular docking ; Monte Carlo ; simulated annealing ; rational drug-design ; dihydrofolate reductase ; proteinase inhibitors ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: We present a method to search for possible binding modes of molecular fragments at a specific site of a potential drug target of known structure. Our method is based on a Monte Carlo (MC) algorithm applied tothe translational and rotational degrees of freedom of the probe fragment. Starting from a randomly generated initial configuration, favorable bindingmodes are generated using a two-step process. An MC run is first prformed in which the energy in the Metropolis algorithm is substituted by a score function that measures the average distance of the probe to the targetsurface. This has the effect of making buried probes move toward the targetsurface and also allows enhanced sampling of deep pockets. In a second MC run, a pairwise atom potential function is used, and the temperature parameter is slowly lowered during the run (Simulated Annealing). We repeat this procedure starting from a large number of different randomly generated initial configurations in order to find all energetically favourable docking modes in a specified region around the target. We test this method using two inhibitor-receptor systems: Streptomyces griseus Proteinase B in complex with the third domain of the ovomucoid inhibitor from turkey, and dihydrofolate reductase from E. Coli in complex with methotrexate. The method could consistently reproduce the complex found in thecrystal structure searching from random initial positions in cubes ranging from 25 Å to 50 Å about the binding site. In the case of SGPB, we were also successful in docking to the native structure. In addition, we were successful in docking small probes in a search that included the entire protein surface. © 1992 Wiley-Liss, Inc.
    Additional Material: 10 Ill.
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    URL: http://dx.doi.org/10.1002/prot.340130304
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    Erratum (1992)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 13 (1992), S. 272-272 
    Details
    ISSN: 0887-3585
    Keywords: Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/prot.340130309
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    Detection of native-like models for amino acid sequences of unknown three-dimensional structure in a data base of known protein conformations (1992)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 13 (1992), S. 258-271 
    Details
    ISSN: 0887-3585
    Keywords: protein folding ; protein modeling ; knowledge-based prediction ; molecular force field ; statistical mechanics ; globins ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: We present an approach which can be used to identify native-like folds in a data base of protein conformations in the absence of any sequence homology to proteins in the data base. The method is based on a knowledge-based force field derived from a set of known protein conformations. A given sequence is mounted on all conformations in the data base andthe associated energies are calculated. Using several conformations and sequences from the globin family we show that the native conformation is identified correctly. In fact the resolution of the force field is high enough to discriminate between a native fold and several closely related conformations. We then apply the procedure to several globins of known sequence but unknown three dimensional structure. The homology of these sequences to globins of known structures in the data base ranges from 49 to 17%. Withone exception we find that for all globin sequences one of the known globinfolds is identified as the most favorable conformation. These results are obtained using a force field derived from a data base devoid of globins of known structure. We briefly discuss useful applications in protein structurlresearch and future development of our approach. © 1992 Wiley-Liss, Inc.
    Additional Material: 6 Ill.
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    URL: http://dx.doi.org/10.1002/prot.340130308
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    Masthead (1992)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 14 (1992) 
    Details
    ISSN: 0887-3585
    Keywords: Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/prot.340140101
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  • 92
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    Pancreatic spasmolytic polypeptide: Crystallization, circular dichroism analysis, and preliminary X-ray diffraction studies (1992)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 13 (1992), S. 364-368 
    Details
    ISSN: 0887-3585
    Keywords: pancreatic spasmolytic polypeptide ; porcine pancreas ; hanging drop vapor diffusion method ; crystallization ; circular dichroism analysis ; porcine insulin ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Pancreatic spasmolytic polypeptide (PSP) isolated from porcine pancreas has been crystallized by the hanging drop vapor diffusion method. Crystals suitable for X-ray diffraction analysis were grown at pH 4.7 from a solution of 6% saturated ammonium sulfate. The space group is orthorhombic I222 or I212121 with unit cell parameters a = 54.38 Å, b = 72.29 Å, and c = 180.85 Å. There are three molecules of PSP per asymmetric unit and a water content of 46.9%. The crystals diffracts to an estimated resolution of 2.7 Å.The far-UV CD spectrum of PSP shows some exceptional features which cannot be accounted for thoroughly in terms of standard secondary structures commonly seen in protein CD spectroscopy. With this limitation, the secondary structure analysis predicts 15% α-helix, between 10 and 20% antiparallel β-strand, 10% parallel β-strand, 15% turn, and 25 to 40% of other structures. © 1992 Wiley-Liss, Inc.
    Additional Material: 4 Ill.
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    URL: http://dx.doi.org/10.1002/prot.340130408
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    Alkaline phosphatase-somatostatin hybrid proteins as probes for somatostatin-14 receptors (1992)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 14 (1992), S. 1-9 
    Details
    ISSN: 0887-3585
    Keywords: protein engineering ; cassette mutagenesis ; peptide hormone ; molecular modeling ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: By inserting appropriate peptide ligands into surface loops on globular proteins, we expect to develop probes for the location, accessibility, and steric and electrostatic environment of these ligand-binding sites on their membrane-bound receptors. Three residues in a loop on the surface of E. coli alkaline phosphatase were substituted by an 18-residue peptide containing the receptor-binding segment of somatostatin-14 without significantly affecting the catalytic properties of the enzyme. This hybrid protein was then used to investigate the ligand-binding site of somatostatin receptors. Tryptic cleavage of the hybrid protein within the inserted sequence, and binding of the hybrid protein to antisomatostatin antibodies demonstrated the surface accessibility of the guest peptide. Both the wild-type enzyme and the hormone-enzyme hybrid displaced 125I-labeled somatostatin from rat brain membrane receptors only at high concentrations. How-ever, chemical cationization of the hybrid protein, which again did not disturb the phosphatase activity, enhanced its receptor-binding potency to a level only 23 times lower than that of somatostatin itself and 280 times higher than that of the cationized wild-type protein. This alkaline phosphatase/somatostatin hybrid protein appears, therefore, to be a suitable starting point for the development of probes for the steric and electrostatic environment of the ligand-binding site of somatostatin receptors. © 1992 Wiley-Liss, Inc.
    Additional Material: 5 Ill.
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    URL: http://dx.doi.org/10.1002/prot.340140103
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    Functional roles of amino acid residues involved in forming the α-helix-turn-α-helix operator DNA binding motif of tet represser from Tn10 (1992)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 14 (1992), S. 168-177 
    Details
    ISSN: 0887-3585
    Keywords: protein structure ; helix-turn-helix motif ; Tet represser ; mutagenesis ; structure predictions ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: The Tn10derived Tet represser contains an amino acid segment with high homology to the α-helix-turn-α-helix motif (HTH) of other DNA binding proteins. The five most conserved amino acids in HTH are probably involved in structural formation of the motif. Their functional role was probed by saturation mutagenesis yielding 95 single amino acid replacement mutants of Tet repressor. Their binding efficiencies to tet operator were quantitatively determined in vivo. All functional mutants contain amino acid substitutions consistent with their proposed role in a HTH. In particular, only the two smallest amino acids (serine, glycine) can substitute a conserved alanine in the proposed first α-helix without loss of activity. The last position of the first α-helix, the second position in the turn, and the fourth position in the second α-helix require mostly hydrophobic residues. The proposed C-terminus of the first α-helix is supported by a more active asparagine compared to glutamine replacement mutant of the wt leucine residue. The turn is located close to the protein surface as indicated by functional lysine and arginine replacements for valine. A glycine residue at the first position in the turn can be replaced by any amino acid yielding mutants with at least residual tet operator affinity. A structural model of the HTH of Tet repressor is presented. © 1992 Wiley-Liss, Inc.
    Additional Material: 5 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/prot.340140204
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  • 95
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    Structural principles for the propeller assembly of β-sheets: The preference for seven-fold symmetry (1992)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 14 (1992), S. 191-201 
    Details
    ISSN: 0887-3585
    Keywords: common protein fold ; protein architecture ; close packing ; p-sheet twist ; galactose oxidase ; influenza virus neuraminidase ; methylamine dehydrogenase ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Twisted β-sheets, packed face to face, may be arranged in circular formation like blades of a propeller or turbine. This β-pro-peller fold has been found in three proteins: that in neuraminidase consists of six β-sheets while those in methylamine dehydrogenase and galactose oxidase are composed of seven β-sheets. A model for multisheet packing in the β-propeller fold is proposed. This model gives both geometrical parameters of the β-propellers composed of different numbers of sheets and patterns of residue packing at their sheet-to-sheet interfaces. All the known β-propeller structures have been analyzed, and the observed geometries and residue packing are found to be in good agreement with those predicted by models. It is shown that unusual seven-fold symmetry is preferable to six- or eight-fold symmetry for propeller-like multisheet assembly. According to the model, a six β-sheet propeller has to have predominantly small residues in the β-strands closed to its sixfold axis, but no strong sequence constraints are necessary for a seven-fold β-propeller. © 1992 Wiley-Liss, Inc.
    Additional Material: 7 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/prot.340140206
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  • 96
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    Crystal structure of the reduced form of p- hydroxybenzoate hydroxylase refined at 2.3 Å resolution (1992)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 14 (1992), S. 178-190 
    Details
    ISSN: 0887-3585
    Keywords: flavoenzymes ; monooxygenase ; FAD ; reduced flavin ; flavin planarity ; Pseudomonas fluorescens ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: The crystal structure of the reduced form of the enzyme p-hydroxybenzoate hydroxylase from Pseudomonasm fluorescens, complexed with its substrate p-hydroxybenzoate, has been obtained by protein X-ray crystallography. Crystals of the reduced form were prepared by soaking crystals of the oxidized enzyme-substrate complex in deaerated mother liquor containing 300-400 mM NADPH. A rapid bleaching of the crystals indicated the reduction of the enzyme-bound FAD by NADPH. This was confirmed by single crystal spectroscopy.X-ray data to 2.3 Å were collected on oscillation films using a rotating anode generator as an X-ray source. After data processing and reduction, restrained least squares refinement using the 1.9 Å structure of the oxidized enzyme-substrate complex as a starting model, yielded a crystallographic R-factor of 14.8% for 11,394 reflections. The final model of the reduced complex contains 3,098 protein atoms, the FAD molecule, the substrate p-hydroxybenzoate and 322 solvent molecules.The structures of the oxidized and reduced forms of the enzyme-substrate complex were found to be very similar. The root-mean-square discrepancy for all atoms between both structures was 0.38 Å. The flavin ring is almost completely planar in the final model, although it was allowed to bend or twist during refinement. The observed angle between the benzene and the pyrimidine ring is 2° This value should be compared with observed values of 10° for the oxidized enzyme-substrate complex and 19° for the enzyme-product complex. The position of the substrate is virtually unaltered with respect to its position in the oxidized enzyme. No trace of a bound NADP+ or NADPH molecule was found. © 1992 Wiley-Liss, Inc.
    Additional Material: 8 Ill.
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    URL: http://dx.doi.org/10.1002/prot.340140205
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  • 97
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    The role of tyrosine 67 in the cytochrome c heme crevice structure studied by semisynthesis (1992)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 14 (1992), S. 202-212 
    Details
    ISSN: 0887-3585
    Keywords: semisynthesis ; protein structure ; ligand binding ; amino acid substitution ; solid-phase peptide synthesis ; hydrophobicity ; reduction potentials ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Tyr-67 of mitochondrial cytochrome c is thought to be involved in important hydrogen bonding interactions in the hydrophobic heme pocket of the protein (Takano, T., Dickerson, R.E. (1981) J. Mol. Biol. 153:95-115). The role of this highly conserved residue in heme pocket stability was studied by comparing properties of semisynthetic (Phe-67) and (p-F-Phe-67) analogs with those of native cytochrome c and a “control” analog, (Hse-65)cytochrome c. The (Phe-67) and (p-F-Phe-67) analogs have well-developed 695-nm visible absorption bands and are active in a cytochrome c oxidase assay. The reduction potentials of both analogs are lower than the native protein by approximately 50 mV. Although both analogs bind imidazole with higher affinity than the native protein, only the (p-F-Phe-67) analog has a 3- to 5-fold lower binding constant for cyanide. Only the (Phe-67) analog was significantly more stable toward alkaline isomerization. These results are not consistent with stabilization of the native protein heme pocket via hydrogen bonding of Tyr-67 to Met-80. An alternative steric role for Tyr-67 is proposed in which the residue controls the heme reduction potential by limiting the number of internal H2O molecules in the heme pocket. © 1992 Wiley-Liss, Inc.
    Additional Material: 2 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/prot.340140207
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  • 98
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    Effects of changing the interaction between subdomains on the thermostability of Bacillus neutral proteases (1992)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 14 (1992), S. 224-236 
    Details
    ISSN: 0887-3585
    Keywords: subdomain ; kinetics ; unfolding ; stabilization ; autolysis ; protein engineering ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Variants of the thermolabile neutral protease (Npr) of B. subtilis (Npr-sub) and the thermostable neutral protease of B. stearothermophilus (Npr-ste) were produced by means of site-directed mutagenesis and the effects of the mutations on thermostability were determined. Mutations were designed to alter the interaction between the middle and C-terminal subdomain of these enzymes. In all Nprs a cluster of hydrophobic contacts centered around residue 315 contributes to this interaction. In thermostable Nprs (like Npr-ste) a 10 residue β-hairpin, covering the domain interface, makes an additional contribution. The hydrophobic residue at position 315 was replaced by smaller amino acids. In addition, the β-hairpin was deleted from Npr-ste and inserted into Npr-sub. The changes in thermostability observed after these mutations confirmed the importance of the hydrophobic cluster and of the β-hairpin for the structural integrity of Nprs. Combined mutants showed that the effects of individual mutations affecting the inter action between the subdomains were not additive. The effects on thermostability decreased as the strength of the subdomain interaction increased. The results show that once the subdomain interface is sufficiently stabilized, additional stabilizing mutations at the same interface do not further increase thermostability. The results are interpreted on the basis of a model for the thermal inactivation of neutral proteases, in which it is assumed that inactivation results from the occurrence of local unfolding processes that render these enzymes susceptible to autolysis. © 1992 Wiley-Liss, Inc.
    Additional Material: 7 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/prot.340140209
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  • 99
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    Fuzzy cluster analysis of molecular dynamics trajectories (1992)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 14 (1992), S. 249-264 
    Details
    ISSN: 0887-3585
    Keywords: fuzzy clustering ; molecular dynamics ; simulations ; nonequilibrium ; protein conformation ; parathyroid hormone (PTH) ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: We propose fuzzy clustering as a method to analyze molecular dynamics (MD) trajectories, especially of proteins and polypeptides. A fuzzy cluster analysis locates classes of similar three-dimensional conformations explored during a molecular dynamics simulation. The method can be readily applied to results from both equilibrium and nonequilibrium simulations, with clustering on either global or local structural parameters. The potential of this technique is illustrated by results from fuzzy cluster analyses of trajectories from MD simulations of various fragments of human parathyroid hormone (PTH). For large molecules, it is more efficient to analyze the clustering of root-mean-square distances between conformations comprising the trajectory. We found that the results of the clustering analysis were unambiguous, in terms of the optimal number of clusters of conformations, for the majority of the trajectories examined. The conformation closest to the cluster center can be chosen as being representative of the class of structures making up the cluster, and can be further analyzed, for example, in terms of its secondary structure. The CPU time used by the cluster analysis was negligible compared to the MD simulation time. © 1992 Wiley-Liss, Inc.
    Additional Material: 5 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/prot.340140211
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  • 100
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    Hydrogen exchange in native and denatured states of hen egg-white lysozyme (1992)
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 14 (1992), S. 237-248 
    Details
    ISSN: 0887-3585
    Keywords: protein folding ; denatured states ; hydrogen exchange ; NMR ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: The hydrogen exchange kinetics of 68 individual amide protons in the native state of hen lysozyme have been measured at pH 7.5 and 30°C by 2D NMR methods. These constitute the most protected subset of amides, with exchange half lives some 105-107 times longer than anticipated from studies of small model peptides. The observed distribution of rates under these conditions can be rationalized to a large extent in terms of the hydrogen bonding of individual amides and their burial from bulk solvent. Exchange rates have also been measured in a reversibly denatured state of lysozyme; this was made possible under very mild conditions, pH 2.0 35°C, by lowering the stability of the native state through selective cleavage of the Cys-6-Cys-127 disulfide crosslink (CM6-127 lysozyme). In this state the exchange rates for the majority of amides approach, within a factor of 5, the values anticipated from small model peptides. For a few amides, however, there is evidence for significant retardation (up to nearly 20-fold) relative to the predicted rates. The pattern of protection observed under these conditions does not reflect the behavior of the protein under strongly native conditions, suggesting that regions of native-like structure do not persist significantly in the denatured state of CM6-127 lysozyme. The pattern of exchange rates from the native protein at high temperature, pH 3.8 69°C, resembles that of the acid-denatured state, suggesting that under these conditions the exchange kinetics are dominated by transient global unfolding. The rates of folding and unfolding under these conditions were determined independently by magnetization transfer NMR methods, enabling the intrinsic exchange rates from the denatured state to be deduced on the basis of this model, under conditions where the predominant equilibrium species is the native state. Again, in the case of most amides these rates showed only limited deviation from those predicted by a simple random coil model. This reinforces the view that these denatured states of lysozyme have little persistent residual order and contrasts with the behavior found for compact partially folded states of proteins, including an intermediate detected transiently during the refolding of hen lysozyme. © 1992 Wiley-Liss, Inc.
    Additional Material: 3 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/prot.340140210
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