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  • 1995-1999  (1,339)
  • 1998  (1,339)
  • Engineering  (644)
  • Organic Chemistry  (362)
  • Rat  (170)
  • Human  (163)
  • Nuclear reactions
  • 1
    ISSN: 1530-0358
    Keywords: Mechanical bowel preparation ; Bacterial translocation ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract PURPOSE: Prospective, randomized studies have shown that bowel preparation may adversely affect infectious complications following colonic resections. However, very little is known about the effects of bacterial translocation on these infectious complications. The aim of this prospective, randomized study was to assess the effects of bowel preparation on bacterial translocation. METHODS: A total of 82 consecutive patients undergoing elective abdominal operations were randomly assigned to four groups: control (I; n=20), mechanical (II; n=21), mechanical plus oral metronidazole (III; n=20), and polyethylene glycol preparation (IV; n=21). Patients with intra-abdominal infection, those receiving preoperative antibiotics for any reason, and those having lower gastrointestinal tract disease were excluded from the study. Peritoneal swab, ileocecal and pericolic mesenteric lymph nodes, liver wedge biopsy, portal venous blood, and peripheral blood samples were taken for culture. Patients were followed up for postoperative infectious complications. Groups were matched according to age, gender, body surface area, and Acute Physiology and Chronic Health Evaluation II scores. RESULTS: Bacterial translocation was identified by a positive culture in one patient in Group I, two in Group II, one in Group III, and three in Group IV, respectively. Differences in number of positive cultures among the groups were not statistically significant. Nine patients had major infectious complications. Only two had bacterial translocation, and the same micro-organisms grew in both patients, in one at the wound site and in the other at the cyst abscess. CONCLUSION: This study demonstrated that mechanical bowel preparation does not enhance the spontaneous occurrence of bacterial translocation in patients without any clinical signs of lower gastrointestinal tract disease.
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  • 2
    ISSN: 1530-0358
    Keywords: Colonic neoplasms/surgery ; Human ; Laparoscopy ; Prospective study
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract PURPOSE: Laparoscopic colorectal surgery for cancer is currently under discussion. Results of large, randomized studies will not be available for a number of years yet. This study analyses the results of such resections in consecutive patients operated on by unselected surgeons. METHODS: A prospective, observational, multicenter study was initiated on August 1, 1995, in the German-speaking countries of Europe. One year after initiation of the study, findings are presented with respect to the quality of oncologic resections. RESULTS: Of 500 operations, 231 (46 percent) were performed for cancer, 167 (33 percent) with a curative intent. The most common curative resections were as follows: 63 anterior rectum resections (38 percent), 51 sigmoid resections (30 percent), and 27 abdominoperineal resections (16 percent). Segmental resections were performed in 20 patients (12 percent). Intraoperative tumor spillage was reported in 2 percent. Mean number of lymph nodes harvested was 13 (confidence interval, 5–95 percent; range, 11.5–14.6) and positive lymph nodes harvested was 2.2 (confidence interval, 5–95 percent; range, 0.9–3.4). Significant differences were noted between participating centers in terms of number of lymph nodes resected (P〈0.0001). Distal and proximal resection margins were tumorfree in every case. Lateral margins were tumor-free when examined. In the case of 63 curative anterior resections, the mean distal resection margin was 39 (confidence interval, 5–95 percent; range, 33–45) mm, and in 8 of these resections, it was less than 20 mm. Mean blood loss was 344 (confidence interval, 5–95 percent; 292–396) ml, and 21 percent of patients received blood transfusions. CONCLUSIONS: These data document that the average quality of laparoscopic colorectal procedures for cancer is satisfactory but differs among surgeons.
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  • 3
    ISSN: 1534-4681
    Keywords: IL-6 ; Metastasis ; Hepatocellular carcinoma ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: Previous studies demonstrated that excess IL-6 production correlated with the metastatic potential of rat hepatocellular carcinoma cells. In the work reported here a retroviral construct containing the gene for murine IL-6 was introduced into otherwise nonmetastatic tumor cells to directly determine the effect of IL-6 overexpression on tumor metastatic potential. Methods: The clonal cell lines 1682.C.2.9.L0 (L0, poorly metastatic) and 1682.C.2.9.L10 (L10, highly metastatic) were selected from a parental hepatocellular carcinoma induced in ACI rats by feeding an ethionine-containing diet. Viral supernatant was used to infect the PA317 amphotropic cell line, and retrovirus produced from these cells infected the poorly metastatic L0 hepatocellular carcinoma cell line. Neomycin-resistant cells were selected in G418 and designated L0-IL-6. Results: As determined by bioassay, L0 cells produce 10±1.2 U/mL IL-6 in culture, whereas L10 cells release 95±11 U/mL (P〈0.01, Student'st-test). Retroviral-mediated IL-6 gene transfer resulted in the production of 1266±48 U/mL IL-6 by L0-IL-6 cells under identical culture conditions. When an inoculum of 5×106 cells is injected subcutaneously, both L0 and L10 cell lines result in primary tumors with equivalent rates of growth; only L10 cells metastasize to the lung, however. A similar inoculation of L0-IL-6 cells produced local tumors in all 24 animals tested. Interestingly, 15 of 24 (62%) animals presented with metastatic nodules in the abdominal cavity, whereas no such tumors were found in animals receiving L10 cells. Conclusion: Overexpression of IL-6 increases metastatic potential of tumor cells, with preferential metastases to the abdominal cavity when compared with tumor cells elaborating endogenous IL-6.
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  • 4
    ISSN: 1435-9456
    Keywords: Key words Attention ; Categorization ; Primate ; Baboon ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract We examined attention shifting in baboons and humans during the learning of visual categories. Within a conditional matching-to-sample task, participants of the two species sequentially learned two two-feature categories which shared a common feature. Results showed that humans encoded both features of the initially learned category, but predominantly only the distinctive feature of the subsequently learned category. Although baboons initially encoded both features of the first category, they ultimately retained only the distinctive features of each category. Empirical data from the two species were analyzed with the 1996 ADIT connectionist model of Kruschke. ADIT fits the baboon data when the attentional shift rate is zero, and the human data when the attentional shift rate is not zero. These empirical and modeling results suggest species differences in learned attention to visual features.
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Surgical and radiologic anatomy 20 (1998), S. 185-189 
    ISSN: 1279-8517
    Keywords: Lateral pterygoid muscle ; Masticatory muscles ; Innervation ; Human ; Anatomy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The one- or two-headed arrangement of the lateral pterygoid m. (LPM) was analysed by studying the motor nerve distribution within the muscular tissue. In all subjects, the main innervation of the lateral pterygoid m. came from the anterior trunk of the mandibular n. by one to three nerves. These nerves divided into five or six vertical branches which ramified into parallel horizontal tiny fibers. Consequently, the lateral pterygoid m. appeared to be divided into oblique sagittal planes and horizontal layers by the nerve branches, reflecting the multipennate organisation of the muscle. These layers can be selectively recruited during mandibular movements, ensuing a fine medial-lateral control. According to its nerve supply, the LPM has to be considered as a single unit made of independent functional musulo-aponeurotic layers even though its morphologic conformation is in one, two or three heads.
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  • 6
    ISSN: 1279-8517
    Keywords: Human ; “Hamstrings” ; Nerve and vascular supply ; Fecal incontinence ; Muscle transposition
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Anal neosphincter formation with electrically stimulated gracilis muscle is used increasingly for the surgical treatment of fecal incontinence. An alternative to gracilis might be of interest if this muscle is not available. 30 semitendinosus muscles and 15 long heads of biceps femoris were investigated on human cadavers. In particular, the nerve and vascular supply of these muscles was studied, both representing basic factors for muscle transposition. The long head of biceps femoris m. was found to receive its dominant vascular supply from the first and second perforating artery and its nerve supply from one motor branch out of the sciatic nerve, both as described in literature. The examination of semitendinosus m., however, revealed new anatomical aspects in its vascular supply. In all cases semitendinosus m. was found to receive dominant vascular pedicles from the medial circumflex femoral artery close to the ischial tuberosity and the second perforating artery. The nerve supply consisted of two motor branches out of the sciatic nerve. Both muscles fulfilled several basic criterias for transposition to the anus. However, regarding these requirements, semitendinosus offered distinct advantages in comparison with the long head of biceps femoris. Due to its vascular and nerve topography, semitendinosus seems suitable to serve as an alternative to gracilis.
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  • 7
    ISSN: 1438-2199
    Keywords: Amino acids ; 14C-l-Serine ; Rat ; Whole body autoradiography ; Accumulation ; Kidney
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The distribution of radioactivities in rats following intravenous administration of14C-d- or -l-serine was investigated by whole body autoradiography. The radioactivities were distributed throughout the whole body in both cases with the greatest amount being found in the pancreas. D- andl- Serine levels in the pancreas were determined by high-performance liquid chromatography with a chiral column which revealed, for the first time, the existence ofd-serine in the rat pancreas (12.6 ± 7.90 nmol/g wet tissue) together with a much higher concentration (924 ± 116 nmol/g) ofl-serine. The results suggested that exogenous D-serine of dietary origin contributed at least in part to the D-serine levels found in mammalian tissues. The accumulation of radioactivity in the kidney, especially in the corticomedullary area, even at 24 hr after administration of14C-l-serine suggested a possible link between acute necrosis of the renal proximal tubules and the administration of a large dose of D-serine [Am J Pathol 77: 269–282 (1974)].
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  • 8
    ISSN: 1438-2199
    Keywords: Amino acids ; In situ hybridization ; Cysteine dioxygenase ; Liver ; Lung ; Kidney ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The expressions of cysteine dioxygenase (CDO) gene in the liver, lung, skeletal muscle, and kidney were studied byin situ hybridization with a cDNA probe from rat liver CDO under normal conditions. Significant expression of the CDO gene was detected in the liver, lung, and kidney, but not skeletal muscle. In the liver, the signal was confined to the cytoplasm of the hepatocytes. Furthermore, the signal was stronger in the periportal than that in the perivenous areas. In the lung, an intensive signal was found in the bronchiolar epithelium. As to the kidney, an intensive signal was observed in the distal convoluted tubules, while no signal was found in the proximal convultions.
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  • 9
    ISSN: 1438-2199
    Keywords: Amino acids ; Taurine ; Rat ; Natriuresis ; Hypotonic saline ; Hypertonic saline
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Male Wistar-Kyoto rats were given either tap water (control) or 3%β-alanine (taurine-depleted) for three weeks. To prepare for the kidney function studies, the animals were then implanted with femoral vessels and bladder catheters. Two days after surgery, each rat was given an intravenous infusion of saline at the rate of 50μl/min and urine samples were collected at specific time intervals. An isotonic saline solution (0.9% NaCl) was infused for determination of baseline parameters and was followed by the infusion of a hypotonic saline solution (0.45% NaCl). Two days later, the infusion protocol was repeated in the same animals; however, a hypertonic saline solution (1.8% NaCl) was substituted for the hypotonic saline solution. Renal excretion of fluid and sodium increased in the control, but not taurine-depleted, rats during the hypotonic saline infusion. Interestingly, diuretic and natriuretic responses were similar between the groups during hypertonic saline infusion. The results suggest that taurine-depletion in rats affects renal excretory responses to a hypotonic, but not a hypertonic, saline solution.
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  • 10
    ISSN: 1438-2199
    Keywords: Amino acids ; Striatal dopamine release ; Intrastriatal taurine ; GABA ; Homotaurine ; Microdialysis ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We studiedin vivo the effects of locally infused taurine (50, 150, and 450 mM) on the striatal dopamine and its metabolites in comparison with those of GABA and homotaurine, a GABAA receptor agonist, in freely moving rats. The extracellular dopamine concentration was elevated maximally 2.5-, 2- and 4-fold by taurine, GABA and homotaurine, respectively. At 150 mM concentration, at which the maximum effects occurred, homotaurine increased the extracellular dopamine more than taurine or GABA. When taurine and GABA were infused simultaneously with tetrodotoxin the output of dopamine did not differ from that in the presence of tetrodotoxin alone. In comparison, tetrodotoxin did not inhibit the increase in extracellular dopamine caused by homotaurine. Furthermore, omission of calcium from the perfusion fluid inhibited the increase of extracellular dopamine caused by GABA. However, it did not block the increase of dopamine caused by taurine or homotaurine. The present study suggests that the effects of intrastriatal taurine, GABA and homotaurine on the striatal extracellular dopamine differ. Thus, these amino acids seem to affect the striatal dopaminergic neurons via more than one mechanism.
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  • 11
    ISSN: 1432-1440
    Keywords: Key words Heart failure ; Human ; RNase protection assay ; Myocardial biopsies ; Gene expression
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  End-stage human heart failure is associated with changes in expression of steady-state messenger RNA (mRNA) levels. These changes correspond to alterations in protein levels and myocardial function and may have clinical implications regarding etiology, clinical state, or prognosis. However, analysis of mRNA levels in endomyocardial biopsies can be accomplished only by the quantitative polymerase chain reaction, which is difficult to standardize. The aim of the study was to evaluate whether the RNase protection assay is applicable to measure mRNAs of multiple genes simultaneously in small amounts of ventricular myocardium comparable to myocardial biopsies. Total RNA was prepared from left ventricular myocardium from terminally failing hearts with idiopathic (n=9) or ischemic cardiomyopathy (n=7) and from nonfailing control hearts (n=10). mRNA was measured by an optimized RNase protection assay for the β1-adrenoceptor, the stimulatory G protein α-subunit (Gsα), phospholamban, the calcium ATPase of the sarcoplasmic reticulum (SERCA), β-myosin heavy chain (β-MHC), and the atrial natriuretic peptide (ANP). We extracted 10.7±2.1 μg total RNA from three myocardial biopsies taken in vitro. All of the six genes were measurable in duplicate in a total of 7 μg RNA. mRNAs of β1-adrenoceptor, phospholamban, and SERCA were lower in failing than in nonfailing myocardium by 50%, 33%, and 42% respectively, whereas β-MHC and Gsα mRNAs were unchanged. mRNA of ANP was expressed at high levels only in the failing myocardium, providing a highly specific and sensitive marker for discriminating nonfailing and failing hearts. A direct comparison with ANP and Gsα levels obtained by Northern blot analysis with 7.5 μg total RNA showed a good correlation between the two methods. The RNase protection assay is thus a suitable method for simultaneous measurements of multiple mRNA levels in human myocardial biopsies. Changes in mRNA levels closely reflected those identified by other methods using larger amounts of RNA. Increased myocardial ANP mRNA levels determined by the RNase protection assay may serve as a molecular marker of heart failure.
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  • 12
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 357 (1998), S. 133-142 
    ISSN: 1432-1912
    Keywords: Key words Intimal hyperplasia ; Potassium chloride ; α1-Adrenoceptor ; Methacholine ; Sodium nitroprusside ; Rat ; Carotid artery
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The influence of neointima formation on functional characteristics was investigated in rat carotid artery preparations. The process of intimal hyperplasia development in the injured carotid arteries was followed in time both morphologically and morphometrically. Simultaneously with the loss of endothelial cells due to the balloon injury procedure, the vasodilator responses to methacholine were abolished. The sensitivity for the α1-adrenoceptor agonist phenylephrine appeared to be increased only immediately after injury. The balloon injury method led to significant neointima formation in the rat left common carotid artery 14 days after the intervention. Eight weeks after balloon injury, the neointimal mass reached its maximum. Parallel to the development of intimal hyperplasia, the α1-mediated vasoconstrictor responses to phenylephrine were significantly impaired. After 12 weeks of observation, reoccurrence of mature endothelial cells on the luminal surface of the neointima could be observed. Simultaneously, the vascular responses to phenylephrine and methacholine recovered. The vasoconstrictor responses to high potassium concentrations (100 mM) as well as the vasodilator effects of sodium nitroprusside appeared to be uninfluenced by balloon injury throughout the period of observation. From this study we conclude that both the receptor-mediated contractile responses to α1-adrenoceptor stimulation and the endothelium-dependent vasodilator responses to methacholine become severely impaired as a consequence of balloon catheter injury followed by intimal hyperplasia. However, these pharmacological responses may fully recover upon a prolonged period of endothelial regeneration.
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  • 13
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 357 (1998), S. 336-343 
    ISSN: 1432-1912
    Keywords: Key words NNK ; Elimination kinetics ; Metabolism ; Perfusion ; Lung ; Liver ; Rat ; N-oxide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The tobacco specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a strong lung carcinogen in all species tested. To elicit its tumorigenic effects NNK requires metabolic activation which is supposed to take place via α-hydroxylation, whereas N-oxidation is suggested to be a detoxification pathway. The differences in the organ specific metabolism of NNK may be crucial for the organotropy in NNK-induced carcinogenesis. Therefore, metabolism of NNK was investigated in the target organ lung and in liver of Fischer 344 (F344) rats using the model of isolated perfused organs. High activity to metabolize 35 nM [5-3H]NNK was observed in both perfused organs. NNK was eliminated by liver substantially faster (clearance 6.9 ± 1.6 ml/min, half-life 14.6 ± 1.2 min) than by lung (clearance 2.1 ± 0.5 ml/min, half-life 47.9 ± 7.4 min). When the clearance is calculated for a gram of organ or for metabolically active cell forms, the risk with respect to carcinogenic mechanisms was higher in lung than in liver. The metabolism of NNK in liver yielded the two products of NNK α-hydroxylation, the 4-oxo-4-(3-pyridyl)-butyric acid (keto acid) and 4-hydroxy-4-(3-pyridyl)-butyric acid (hydroxy acid). In lung, the major metabolite of NNK was 4-(methylnitrosamino)-1-(3-pyridyl-N-oxide)-1-butanone (NNK-N-oxide). Substantial amounts of metabolites formed from methyl hydroxylation of NNK, which is one of the two possible pathways of α-hydroxylation, were detected in lung but not in liver perfusion. Formation of these metabolites (4-oxo-4-(3-pyridyl)-butanol (keto alcohol), and 4-hydroxy-4-(3-pyridyl)-butanol (diol) can give rise to pyridyloxobutylating of DNA. When isolated rat livers were perfused with 150 μM NNK, equal to a dosage which is sufficient to induce liver tumors in rat, glucuronidation of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) was increased when compared to the concentration of 35 nM NNK. Nevertheless, the main part of NNK was also transformed via α-hydroxylation for this high concentration of NNK.
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  • 14
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 357 (1998), S. 593-599 
    ISSN: 1432-1912
    Keywords: Key words d-amphetamine ; Dopamine receptors ; Locomotor activity ; Raclopride ; SCH-23390 ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In d-amphetamine-treated (4.0 mg kg–1 s.c.) rats the selective dopamine D1 and D2/3 receptor antagonists SCH-23390 (2.5–20.0 µg kg–1 s.c.) and raclopride (12.5–100.0 µg kg–1 s.c.), respectively, produced a biphasic pattern of effects on forward locomotion, as observed in an open-field arena (≈0.5 m2). Thus, at the low doses of SCH-23390 (2.5–10.0 µg kg–1) or raclopride (12.5–50.0 µg kg–1), there was a statistically significant increase in forward locomotion, followed by suppression of the behavior at the higher doses. The SCH-23390-induced (5.0 µg kg–1) stimulation of forward locomotion was partially antagonized by concomitant raclopride treatment (12.5–25.0 µg kg–1) and the corresponding raclopride-induced (12.5 µg kg–1) stimulation was fully antagonized by treatment with SCH-23390 (2.5–5.0 µg kg–1). Furthermore, the SCH-23390- or raclopride-induced stimulation of forward locomotion was also antagonized by treatment with the α1-adrenoceptor antagonist prazosin (1.0 mg kg–1 s.c.). These observations suggest that under conditions of an increased general tone at brain dopamine receptors, there is a mutual inhibitory synergy between dopamine D1 and D2/3 receptors.
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  • 15
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 357 (1998), S. 671-676 
    ISSN: 1432-1912
    Keywords: Key words Gastric emptying ; Nitric oxide ; Pregnancy ; Gastric fundus ; Pylorus ; Non-adrenergic non-cholinergic ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The influence of pregnancy on the role of nitric oxide (NO) in gastric emptying and in non-adrenergic non-cholinergic (NANC) relaxation was studied in rats. The gastric emptying of a non-nutrient liquid solution and of polysterene beads was studied in non-pregnant (NP), 6 to 7 days pregnant (P7) and 18 to 20 days pregnant (P20) rats. Longitudinal muscle strips of the gastric fundus and circular muscle strips of the pylorus were isolated from NP and P20 rats and NANC relaxations were induced by electrical field stimulation. The gastric emptying of the liquid meal was significantly increased in P20 rats as compared to NP and P7 rats. In NP rats, NG-nitro-L-arginine methyl ester (L-NAME) dose-dependently (50–150 mg/kg ip) reduced the gastric liquid emptying; the inhibitory effect of 100 mg/kg L-NAME ip was prevented by 400 mg/kg ip L-arginine and was mimicked by 100 mg/kg NG-monomethyl-L-arginine (L-NMMA). The percentage inhibition of the liquid emptying by L-NAME did not differ between the 3 groups, except for the dose of 150 mg/kg ip where it was significantly lower in P20 rats. The gastric emptying of beads was 54% in NP, 36% in P7 and 69% in P20 rats but these values were not significantly different illustrating the great variability. The inhibitory effect of L-NAME (25 and 100 mg/kg ip) on the emptying of beads did not differ between the 3 groups. As evaluated in NP rats, the inhibitory effect of L-NAME on the gastric emptying of the beads was not prevented by L-arginine nor mimicked by L–NMMA. Electrical field stimulation in NANC conditions induced frequency-dependent relaxations in the fundus strips and relaxations followed by rebound contractions in the pyloric strips. These electrically induced NANC relaxations and their reduction by 3×10–4 M L-NAME were not different between NP and P20 rats. It can be concluded that no evidence for a regulatory role of NO in the gastric emptying of the beads was found, and that the nitrergic contribution to the gastric emptying of liquids and to the fundic and pyloric NANC relaxations was not influenced by pregnancy in rats.
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  • 16
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 357 (1998), S. 701-704 
    ISSN: 1432-1912
    Keywords: Key words Oxytocin ; Rat ; Musculocutaneous flap ; Wound healing ; Oxytocin antagonist ; Growth factors ; IGF-1
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The aim of the present study was to evaluate the effect of oxytocin on survival of musculocutaneous flaps in male Sprague-Dawley rats. For this purpose oxytocin (0.1 or 1.0 mg/kg), an oxytocin antagonist (1-deamino-2-D-Tyr-(OEt)-4-Thr-8-Orn-oxytocin) (1.0 mg/kg) alone or in combination with oxytocin (1.0 mg/kg) or saline was given subcutaneously (s.c.), 24 hours and 1 hour before and 24 hours after flap surgery. In addition, oxytocin (1 µg/kg) or saline was given intracerebroventricularly (i.c.v.) according to the same schedule. Six days after surgery the amount of viable tissue was measured. Oxytocin 1.0 (but not 0.1) mg/kg s.c. and 1.0 µg/kg i.c.v. increased survival of the flaps (s.c.: 13.8±14.6% versus 6.10±5.45%; p〈0.05 and i.c.v.: 25.5±14.0% versus 10.3±5.79%; p〈0.01). This effect was abolished by the oxytocin antagonist. Furthermore, the oxytocin-treated rats had significantly higher plasma levels of insulin-like growth factor-1 (IGF-1) (p〈0.05). These data indicate that oxytocin increases the survival of musculocutaneous flaps. The effect seems to be exerted within the central nervous system since a 1000 fold lower dose of oxytocin given i.c.v. increased flap survival to the same extent as the s.c. given dose. IGF-1 might be one of the mediators of this effect.
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  • 17
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    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 357 (1998), S. 413-418 
    ISSN: 1432-1912
    Keywords: Key words PBR ; Kainate ; Reactive oxygen species ; Glutamate ; U-83836E ; Mitochondria ; Cerebellum ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effect of kainic acid (KA) on mitochondrial membrane potential (MMP) and reactive-oxygen species (ROS) production was studied in dissociated cerebellar granule cells from rat pups. KA induced a maximum increase of 361%±35% in ROS production. The lazaroid compound U-83836E (at concentrations ranging from 10–9 to 5×10–6M) completely inhibited this increase, with an IC50 value of 3.02±1.08×10–7M. KA also decreased the mitochondrial membrane potential (MMP), with a maximum decrease of about 30%. Absence of Na+ in the incubation medium did not significantly alter the effect of KA on MMP. As expected, the AMPA/kainate receptor antagonist NBQX inhibited the effects of KA on MMP with an IC50 value of 1.1±0.8μM. However, the lazaroid U-83836E, indomethacin, nor-dihydroguaiaretic acid and L-nitroarginine all failed to inhibit the KA-induced decrease in the MMP. Finally, to assess the neuroprotective effect of U-83836E on KA-induced neurotoxicityin vivo, the increase in the peripheral-type benzodiazepine receptor density in rat hippocampus was measured. Treatment with KA increased the Bmax to 1341±192fmol mg–1. When U-83836E was coadministered with KA, the Bmax was reduced to 765±122fmol mg–1, which was not significantly different from the Bmax obtained from untreated rats (Bmax: 518±33fmol mg–1). We conclude that treatment with the lazaroid U-83836E might be a suitable therapeutic strategy in neurodegenerative disorders.
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  • 18
    ISSN: 1432-0843
    Keywords: Key words Topoisomerase II ; Human ; Yeast ; Antitumour drugs ; Bisdioxopiperazine compounds ; ICRF-193
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose: To identify and characterize the specificity and potency of topoisomerase II-interacting antitumour drugs in an in vivo model utilizing the yeast Saccharomyces cerevisiae. Methods: Four yeast transformants were selected for the expression of either human or yeast DNA topoisomerase II at different, biologically relevant, levels under the tight control of promoters of various strengths. Results: Analyses of 24 drugs permitted their classification into three distinct groups, depending on whether they induced topoisomerase II-related cytotoxicity (etoposide), showed nonspecific cytotoxicity (camptothecin), or exerted no cytotoxicity at all (vinorelbine). Within the first group different patterns of action were distinguishable: (1) classical topoisomerase II expression-dependent cytotoxicity for both species of enzyme (e.g. etoposide, amsacrine, doxorubicin, actinomycin D), although amsacrine and TOP 53 were more active, respectively, on human and yeast topoisomerase II; and (2) compounds that appeared to poison only one species of topoisomerase II with, for example, genistein and the bisdioxopiperazine ICRF-193 lethally targeting only the human type, and mitoxantrone only the yeast isozyme. Three of the 16 known topoisomerase II inhibitors tested were not correctly identified with this assay, possibly owing to restricted cell wall permeability or to the absence of correct processing pathways such as, for example, in the case of the prodrug etopophos. Conclusion: This methodology, in vivo in yeast, selected for a large range of potent topoisomerase II-targeting anticancer agents. Of particular interest in this yeast model, and in contrast to yeast topoisomerase II, human topoisomerase II was shown to confer dominant sensitivity in the presence of the series of bisdioxopiperazine derivatives tested. This assay therefore has the potential easily to identify and characterize the potency and specificity of synthesized anticancer drugs with modified original chemical structures or those present, for example, in natural plant extracts or marine organisms.
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  • 19
    ISSN: 1437-9813
    Keywords: Key words Fetal transplantation ; Adrenals ; Addisonian crises ; Rat ; Adrenocorticotropic hormone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The present study investigates whether fetal adrenal transplants into the omentum of adrenalectomized rats will be integrated into the recipient's endocrine system to provide competent adrenocortical function. The results demonstrate that fetal adrenals graft with a rich vascular supply, mature histologically, and produce increasing levels of corticosterone. When bilateral adrenalectomy is performed in the recipient, survival is prolonged and addisonian crisis can be prevented. Moreover, adrenocorticotrophic hormone levels decrease with increasing levels of corticosterone, indicating that the fetal grafts are integrated into the physiological pituitary-adrenocortical feedback system.
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  • 20
    ISSN: 1432-2307
    Keywords: Key words Monoclonal antibody ; Multidrug resistance ; P-Glycoprotein peptide ; Mouse ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  A novel immunization protocol together with stringent selection criteria have been employed to generate a new murine monoclonal antibody (’’D8’’, isotype IgG1, kappa) which specifically recognizes the human p170 drug resistance glycoprotein. This antibody is directed towards a defined peptide sequence located in the −COOH terminal region of the first external loop of the molecule. It is reactive with its epitope within the intact native glycoprotein in formalin-fixed and conventionally processed histological tissues, in flow-cytometric preparations and by Western blotting. The antibody precipitates its target peptide sequence from solution, and thus may be a useful reagent with which to establish an ELISA, RIMA or other similar assay. The peptide epitope recognized by this monoclonal antibody is restricted to the human MDR1 gene product and is not contained within the rodent homologue of the P-170 molecule. Immunohistochemistry has consistently failed to detect this epitope in rodent tissues, thus confirming that it does not exhibit the cross-reactivity of other currently available anti-P-glycoprotein monoclonal antibodies. The experience of this study emphasizes the value of the tuberculin-PPD (purified protein derivative) immunization protocol as a powerful strategy when generating monoclonal antibodies to small synthetic peptides. The resulting monoclonal antibody (D8) will be an invaluable reagent with which to analyse P-170 glycoprotein expression when assessing the role of multidrug resistance in human cancers.
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  • 21
    ISSN: 1434-0879
    Keywords: Key words Testicular function ; Smoking ; Fertility ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We evaluated the effects of smoking on testicular function and fertilizing potential in rats. Twenty rats (group A) were exposed to the smoke of 20 cigarettes for 1 h per day. Ten rats (group B) were exposed to the smoke of 40 incense sticks for 1 h per day, and an additional 10 rats served as a control group (group C). After 10 weeks of daily exposure, serum levels of nicotine and cotinine were assessed, and a mating test was conducted. Five days later, serum concentrations of testosterone before and after human chorionic gonadotropin (hCG) stimulation, gonadotropins, and epididymal sperm content and motility were evaluated. In addition, in vitro fertilization was carried out. Nicotine and cotinine were detected in group A, but not in groups B and C. Basal serum testosterone and gonadotropin concentrations did not differ significantly among the three groups, but the testosterone response to hCG stimulation was significantly lower in group A than in groups B and C. Group A showed significant reductions in epididymal sperm content and motility, and in fertility in vivo and in vitro. These findings suggest that smoking leads to a secretory dysfunction of the Leydig cells, and also a deficiency in sperm maturation and spermatogenesis. In addition, smoking has a detrimental effect on sperm fertilizing potentials in vivo and in vitro.
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  • 22
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    Urological research 26 (1998), S. 325-330 
    ISSN: 1434-0879
    Keywords: Key words Urinary bladder ; Obstruction ; Hypertrophy ; Cystometry ; Atropine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The urodynamic effects of an experimental, partial infravesical outlet obstruction in rats were studied and compared with the effects in sham-operated controls, and in animals that had undergone 24 h of total outlet obstruction. The animals were studied up to 42 days after surgery. Bladder weight increased with time in the partially obstructed group to reach a final value of 6 times that of the control. In water loading experiments micturition volume was unaffected by sham operation. In the partially obstructed bladders it decreased initially but normalized with time. In the group that had undergone 24 h of total obstruction micturition volume also decreased initially but then became significantly higher than in the controls. In cystometry experiments the partially obstructed bladders developed a considerable residual urine and increased threshold and micturition pressures. Detrusor instability was present already after 10 days. Also in the cystometry experiments the bladders that had been totally obstructed for 24 h had increased micturition volumes. Residual volume was only slightly affected by atropine in the control and partially obstructed bladders but increased 7-fold in rats in which the bladder had been totally obstructed for 24 h 42 days previously. We conclude that there is a close relationship between bladder weight, residual volume and micturition pressure in the partially obstructed bladder, and that 24 h of total obstruction results in disturbances of bladder function that might be related to denervation phenomena previously reported by others.
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  • 23
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    Urological research 26 (1998), S. 291-297 
    ISSN: 1434-0879
    Keywords: Key words Urinary bladder ; Rat ; Pelvic ganglion ; Innervation ; Denervation ; Plasticity ; Age
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We evaluated the degree of neuronal plasticity following a partial denervation of the rat urinary bladder. Using acetylcholinesterase staining we found that the postganglionic nerves from the pelvic ganglion reach the intact bladder as 1–4 nerve trunks on each side, slightly ventral and caudal to the ureteral orifices. Normally a few thinner nerves also reach the bladder posterolateral to the ureterovesical junction. The nerves ventral to the ureters run in the ventral longitudinal muscle layer as well-defined trunks with a pattern that does not differ much from one animal to another. The nerves reaching the bladder dorsolaterally innervate the dorsolateral aspects in a more irregular fashion. Some anastomoses are found across the midline between nerves from either side. This nerve pattern is already in place in newborn rats. After removal of the pelvic ganglion on one side in the adult rat the ipsilateral ventral nerves rapidly degenerate, whereas some dorsolateral␣nerves usually survive. Axons from the intact ventral␣nerves can be seen crossing over to the denervated side in the anastomoses. After 13 weeks the surviving ventral nerves, which normally run at some distance from the ventral midline, now run in the midline with equal amounts of ventral longitudinal muscle on either side, and with their branches evenly distributed to both sides. The same pattern is seen after 27 weeks. Unilateral ganglionectomy in 3-week-old rats leads to the same changes in nerve distribution as in the adult rat. We conclude that there is a high degree of plasticity in the bladder innervation following a partial denervation, and that this plasticity includes the distribution of its main intramural nerve trunks.
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  • 24
    ISSN: 1432-0533
    Keywords: Key words Endothelial barrier antigen ; Blood-brain ; barrier ; Immunohistochemistry ; Rat ; Spinal cord
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The endothelial barrier antigen (EBA) recognised by a monoclonal antibody is expressed in rat cerebral microvessels possessing blood-brain barrier properties but only weakly by fenestrated vessels. We have studied the expression of this marker in the spinal cord of control rats and compared the findings with those seen in rats subjected to compression injury at the T8–9 level with a survival period of 4 h, 24 h, 4 days and 9 days. To that end, formalin-fixed paraffin-embedded material was immunostained by the avidin-biotin-peroxidase complex method. Sections from control rats presented a distinct immunostaining at the site of the endothelial cells of almost all microvessels in the grey and white matter of the cord. The anterior and posterior spinal arteries did not show such staining. Neurons and glial cells were unstained. Rats which had survived 4 h after a moderate or severe compression trauma still showed immunoreactivity in intramedullary microvessels at the site of injury. There was a moderate reduction of vascular immunoreactivity at 24 h and a pronounced loss of such reactivity at 4 days after trauma. At 9 days after compression the expression of the endothelial barrier antigen had almost been normalised in the microvessels of the cord. In conclusion, using immunohistochemistry, EBA can be demonstrated in noninjured rat spinal cord microvessels, while the staining disappears at the site of compression trauma to the cord. The EBA marker can be used to indicate sites of vascular injury in spinal cord compression injury. The factors causing the disappearance and restitution of the antigen are unknown.
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  • 25
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    Acta neuropathologica 96 (1998), S. 22-28 
    ISSN: 1432-0533
    Keywords: Key words Cerebral arteries ; Human ; Immunohistochemistry ; Vasa vasorum ; Atherosclerosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Vasa vasorum are adventitial vessels that play a role in pathogenesis of atherosclerosis, aneurysm, vasculitides, and graft vascular disease. The existence of vasa vasorum in human intracranial arteries is not yet well defined. The specific aims of this study are to determine whether the human intracranial arteries have vasa vasorum, whether their existence is related to the thickness of tunica media as is in systemic vessels, and whether they are acquired in reaction to pathological conditions, such as atherosclerosis and arterial occlusion. Human intracranial internal carotid (i-ICA), vertebral (i-VA), basilar (BA) and middle cerebral arteries (MCA) from adults, children and newborns were examined. Systemic vessels of comparable medial thickness were used as controls. Immunohistochemical staining for Factor VIII and CD 31 was used to identify the endothelial cells. Human intracranial arteries in neonates, children and adults do not have vasa vasorum, although their medial thickness is comparable to their systemic counterparts with vasa vasorum. Only in adults did the proximal intracranial segments of i-ICA and i-VA reveal a few vasa vasorum-like vessels with unusually large diameter. They were more frequently seen in atherosclerosis and thrombotic but again limited to the proximal segments of i-ICA and i-VA. Completely obstructed bilateral carotid arteries in a child with sickle cell disorder revealed a rich adventitial neovascularization in the proximal intracranial part of the vessel. It is not yet known whether obstruction of the distal segments may create similar neovascularizations. Adventitial neovascularizations seen in the proximal i-ICA and i-VA may represent a focal intracranial extension of the vascular pathologies involving the extracranial segments of major cerebral arteries.
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  • 26
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    Anatomy and embryology 198 (1998), S. 331-339 
    ISSN: 1432-0568
    Keywords: Key words Accessory olfactory bulb ; Vomeronasal epithelium ; Vomeronasal nerves ; Glycoproteins ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  A number of previous studies have indicated that lectin histochemistry is an obvious choice for characterizing the vomeronasal system. However, apparently inconsistent results have been obtained: notably, the affinity with which various lectins bind to the accessory olfactory bulb varies among taxa, even considering closely related species. In the present study, the binding patterns of seven lectins in the rat accessory olfactory bulb, vomeronasal nerves and vomeronasal duct were investigated. The Bandeiraea simplicifolia lectin bound exclusively to the vomeronasal nerve and glomerular layers of the accessory olfactory bulb, while the Ulex europeus and Lycopersicon esculentum lectins bound to these regions and additionally to the nerve and glomerular layers of the main olfactory bulb. Soybean agglutinin showed a similar pattern to that obtained with the Ulex europeus and Lycopersicon esculentum lectins, though it also faintly labelled other parts of the structures examined. The Vicia villosa and Erythrina cristagalli lectins were not specific for the vomeronasal system, since they labelled grey and white matters in structures including the lateral olfactory tract and the anterior olfactory nuclei. The Dolichos biflorus lectin did not bind to vomeronasal tissues. The observed patterns of binding in the accessory olfactory bulb were consistent with those observed in the vomeronasal nerves, but unlike those observed in the epithelium of the vomeronasal duct. This latter result probably reflects binding of lectins to sugar residues contained in secreted mucus rather than those in epithelial nerve endings.
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  • 27
    ISSN: 1432-0568
    Keywords: Key words Pituitary adenylate cyclase-activating peptide (PACAP) ; Small intestine ; Large intestine ; Enteric nervous system ; Rat ; Immunohistochemistry ; Synapse
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Pituitary adenylate cyclase-activating peptide (PACAP)-immunoreactive (IR) neurons in the myenteric and submucosal plexus of the rat small and large intestine were examined by immunostaining with purified polyclonal antiserum against PACAP (1–15), using both light and electron microscopy. Many PACAP-IR neuronal cell bodies and fibers were found in the myenteric and submucosal plexus. Many of the PACAP-IR fibers originated from the cell bodies of the myenteric and submucosal ganglia. The ganglia were also innervated by PACAP-IR fibers. PACAP-IR fibers penetrated both the circular and longitudinal muscle layers, confirming the previous observations indicating that PACAP neurons act as motor neurons. Ultrastructural study demonstrated that PACAP-IR nerve terminals formed synaptic contacts with PACAP-IR nerve cell bodies or dendritic processes. This observation suggests that PACAP-IR neurons innervate other PACAP-IR neurons, and that PACAP neurons work as interneurons in the enteric nervous system. PACAP-IR nerve cells received not only PACAP-positive nerve terminal input also PACAP-negative nerve terminal input. It also suggests that PACAP neurons are regulated not only by PACAP-IR enteric neurons, but also by neurons originating elsewhere. Our observations support the view that PACAP-IR neurons are involved in the control of gut motility.
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  • 28
    ISSN: 1432-0533
    Keywords: Key words B-50(GAP-43) ; Spinal cord ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract B-50(GAP-43) is a phosphoprotein mainly found in the nervous system which plays a major role in neurite growth during development and regeneration as well as in synaptic remodelling. In the mature intact central nervous system, intense B-50 immunoreactivity (B-50-IR) can still be detected in regions which maintain residual capacity for structural re-organization. B-50 expression has been studied extensively in laboratory animals; however, its distribution and regulation in the human spinal cord is largely unknown. As a first step to analyze lesion-induced structural alterations, we investigated the distribution of B-50 protein and mRNA in the normal adult human spinal cord and dorsal root ganglia. Intense B-50-IR was localized to the superficial laminae of the dorsal horn at all segmental levels, the intermediolateral nucleus at thoracic levels and Onuf’s nucleus at sacral levels. Scattered neurons, particularly in the ventral horn of lumbar and sacral segmental levels (and occasionally also in Clarke’s nucleus) displayed intense B-50-IR in close apposition to the perikaryal and proximal dendritic surfaces. Nonradioactive in situ hybridization indicated that B-50 mRNA could also be detected in neurons of the ventral horn and also in the intermediolateral nucleus. The distribution of B-50 mRNA and protein in the normal human spinal cord shows a marked similarity to that reported in experimental animals, including the selective labelling of Onuf’s nucleus. However, the strong B-50-IR on the surface of some large anterior horn motor neurons has not been observed in other mammals. This finding might reflect a particular state of readiness for synaptic plasticity.
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  • 29
    ISSN: 1432-0533
    Keywords: Key words Glucose ; Selective vulnerability ; Isolectin ; Glial fibrillary acidic protein ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We undertook a detailed characterization of the cellular responses to acute global cerebral ischemia complicated by hyperglycemia. Anesthetized, physiologically monitored male Wistar rats received 12.5 min of global forebrain ischemia by bilateral common carotid artery occlusions plus hemorrhagic hypotension to 45 mm Hg. Cranial temperature was maintained at normothermic levels. Hyperglycemic animals received dextrose (2.5 ml of a 25% solution, intraperitoneally) prior to ischemia; this doubled the mean plasma glucose concentration to 296 mg/100 ml. At 3 days (n = 10) or 24 h (n = 4) after ischemia, brains were perfusion-fixed and paraffin-embedded for light microscopic histopathology and for the histochemical visualization of activated microglia and the immunocytochemical visualization of glial fibrillary acid protein. Normal-neuron counts in the vulnerable hippocampal CA1 sector of hyperglycemic-ischemic (HI) rats were reduced to one-third the number observed in normoglycemic-ischemic (NI) animals. Ischemic cell counts in the striatum were increased fivefold or more in HI compared to NI rats, and normal small-neuron counts were reduced by two-thirds. The neocortex and striatum of NI rats showed only mild damage, while the majority of HI rats had extensive lesions, and several showed large cortical, striatal or thalamic infarcts. In addition, widespread cortical ischemic neuronal changes were evident in HI animals. No endothelial alterations were present in NI rats. By contrast, HI rats showed prominent peri- and intravascular polymorphonuclear and monocytic accumulation evident at 24 h; frequent white cell thrombi in pial arterioles on day 3; and thickening of vascular endothelium, with foci of parenchymal rarefaction or microinfarction adjacent to occluded vessels. Prominent microglial activation, often along the course of penetrating blood vessels, was common in the striatum and neocortex of HI animals but was much less extensive in the NI group. Activated microglia in HI rats were typically hypertrophic and amoeboid. These results suggest that the detrimental influence of hyperglycemia in ischemia is initially mediated by an action on vascular endothelium, which in turn leads to widespread foci of infarction and neuronal loss.
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  • 30
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    Acta neuropathologica 96 (1998), S. 351-356 
    ISSN: 1432-0533
    Keywords: Key words Apoptosis ; Hyperthermia ; Glioma ; Rat ; c-Jun
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Hyperthermia has been shown to inhibit glioma growth both in vitro and in vivo, and has been reported to induce apoptosis of a variety of cells. We investigated the role of apoptosis in tumor cell death following hyperthermia in a rat glioma model representing human glioblastoma. Apoptotic cell death was evaluated by terminal deoxyribonucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) and hematoxylin and eosin (H & E) staining. We also examined c-Jun expression immunohistochemically. Apoptotic cell death in rat brain tumors that grew after implantation of C6 glioma cells showed regional differences. In all rats, apoptotic cells, characterized by extreme chromatin condensation and fragmented nuclei with apoptotic bodies in H & E-stained sections, were observed in the gliomas’ necrotic cores. TUNEL-positive cells were observed in the border zones between necrotic and vital tumor cells. Before hyperthermia, TUNEL-positive cells were sporadically distributed in the vital tumor tissue. After hyperthermia, the number of TUNEL-positive cells in the peripheral region of the tumor mass increased significantly, reached a peak after 6 h and returned to the basal level within 24 h (P 〈 0.01). C-Jun protein immunoreactivity was not observed in the cells at the tumor periphery. These data indicate that significantly apoptotic cell death unrelated to c-Jun expression occurs after hyperthermia, and that this form of cell death may be the mechanism of tumor regression following hyperthermia treatment of intracranial gliomas.
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  • 31
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    Anatomy and embryology 198 (1998), S. 53-61 
    ISSN: 1432-0568
    Keywords: Key words Regenerating spermatogonia ; Asymmetric divisions ; Cytoplasmic bridges ; Busulfan ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  This study describes the morphological behaviour of spermatogonia following recovery from two doses of busulfan treatment in the rat. Twenty days after the second intraperitoneal injection of busulfan, the testes lost most of their spermatogenic cells and there were fewer dispersed singly surviving spermatogonia. These surviving cells were in close contact with the basal portions of adjacent Sertoli cells and the shrunken basal lamina, and were the source for repopulating the depleted seminiferous epithelium. During the initial stage of repopulation (48 days later), surviving spermatogonia underwent a phase of active proliferation: type A spermatogonia underwent symmetric and asymmetric divisions; type B spermatogonia underwent asynchronous differentiation. At day 96, normal spermatogenesis was fully recovered in many seminiferous tubules, represented by 80% of the rats regaining various degrees of fertility at day 120. These data provide an additional model for the study of self-renewal of stem spermatogonia and suggest that the asymmetric division of type A spermatogonia and their close contact with both the basal lamina and the Sertoli cells may be involved in regulating the number of stem spermatogonia and the delicate process of normal spermatogenesis.
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  • 32
    ISSN: 1432-0533
    Keywords: Key words Autoantibody ; Ganglioside ; Guillain-Barré ; Human ; Neuropathy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A series of monoclonal IgM anti-GM1 ganglioside antibodies has been cloned from peripheral blood lymphocytes of patients with multifocal motor neuropathy and Guillain-Barré syndrome. In solid-phase immunoassay, the antibodies react with GM1, and also in differing degrees to the structurally related glycolipids asialo-GM1 (GA1) and GD1b. Here we describe the binding patterns of six human anti-GM1 antibodies to epitopes within the human nervous system. Antibodies were observed to bind to motor neurons and spinal grey matter, dorsal and ventral spinal roots, dorsal root ganglion neurons, nodes of Ranvier, neuromuscular junctions and skeletal muscle. The distribution of immunoreactive epitopes, which included sensory structures, extended beyond those sites conventionally regarded as pathologically affected in anti-GM1 antibody-associated motor nerve syndromes. This undermines a model of disease pathogenesis based solely on antigen distribution. Factors other than the presence or absence of antigen, such as the local ganglioside topography, antibody penetration into, and pathophysiological vulnerability of a particular site may also influence the clinicopathological outcome of anti-GM1 antibody-mediated autoimmune attack.
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  • 33
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    Acta neuropathologica 96 (1998), S. 151-156 
    ISSN: 1432-0533
    Keywords: Key words Neuropathy ; Hypoglycemia ; Insulin ; implant ; Rat ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Insulin-dependent diabetes mellitus is a chronic metabolic disease that causes long-term secondary complications such as neuropathy. The occurrence of diabetic neuropathy has generally been thought of as being associated with hyperglycaemia. However, in a previous light microscopic examination of plantar nerves in diabetic BB/Wor rats treated with insulin implants we found that eu-/hyperglycaemic rats present a normal picture, whereas eu-/hypoglycaemic rats show severe changes. The aim of the present work is to supplement our previous light microscopic report with electron microsocpic data from the lateral plantar nerve of normal, eu-/hyperglycaemic and eu-/hypoglycaemic BB/Wor rats. Under the electron microscope lateral plantar nerves collected from eu-/hyperglycaemic rats presented a qualitatively normal picture. In addition, the fibre numbers and the size distribution of the myelinated fibres were normal. In contrast, specimens from eu-/hypoglycaemic BB/Wor rats showed severe qualitative changes, interpreted as signs of axonal de- and regeneration. The total number of axons was somewhat subnormal and the sizes of the myelinated fibres were strongly shifted towards smaller diameters. These data confirm our previous light microscopic observations. We conclude that eu-/hypoglycaemic BB/Wor rats treated with insulin implants, but not similarly treated eu-/hyperglycaemic animals, develop a neuropathy in their plantar nerves.
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  • 34
    ISSN: 1432-0568
    Keywords: Key words Claustrum ; Visual cortex ; Visual zones Comparative anatomy ; Rat ; Guinea pig ; Rabbit ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The retrograde axonal transport method was used to compare the topography and organization of the visual zone of the claustrum in rat, guinea pig, rabbit and cat. First, massive Fluoro-Gold injections were placed into the primary visual cortex and the secondary areas. Experiments showed differences in the location of the visual zone among the animals under study. In rat, the visual zone occupied the posteroventral part of the claustrum and spread to its anterior pole. In guinea pig, neurons projecting to the visual cortex were located dorsally in the posterior half of the claustrum. In rabbit, similarly to the rat, they were localized in the posteroventral part; however, they did not reach the anterior pole. In cat, neurons that project to the visual cortex were concentrated dorsally in the posterior fourth of the claustrum. In double-injection experiments, Fast Blue and Diamidino Yellow were placed into the primary and secondary visual areas in various combinations. The experiments showed that in the rat and the rabbit claustral neurons project to primary visual cortex (area 17) as well as to both secondary visual areas (areas 18a and b). Populations of neurons sending axons to the primary and secondary areas showed full overlap. The presence of double-labeled neurons indicates that some claustral neurons project both to the primary and secondary fields. In cat, neurons that project to the primary visual cortex appear to be clearly separated from those connected with the secondary visual area, as no double-labeled neurons were found. In all studied species, the double injections placed into the visual and primary somatosensory cortex did not result in any double-labeling neurons. Our results indicate that the location of the visual zone in the posterior part of the claustrum is a phylogenetically stable feature, whereas its dorsoventral shift as well as the extent toward the anterior pole is related to the particular species. The overlap of neurons projecting to the primary and secondary visual areas in the rat and rabbit as well as the separation of both projections in cat appear to reflect the higher degree of complexity of the visual system in the latter.
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  • 35
    ISSN: 1432-0533
    Keywords: Key words Non-astrocytic brain tumors ; p53 mutation ; Yeast functional assay ; Malignant lymphoma ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract While it is established that p53 mutation plays a critical role in the carcinogenesis of astrocytic brain tumors, its role remains to be clarified for other types of tumors in the central nervous system (CNS). Using a yeast-based assay which tests the ability of human p53 to activate transcription, we analyzed p53 mutations in 85 non-astrocytic CNS tumors, including 4 benign neuronal tumors (3 central neurocytomas and 1 pineocytoma), 12 primitive neuroectodermal tumors, 14 germ cell tumors (7 germinomas, 7 non-germinomatous tumors), 4 craniopharyngiomas, 14 ependymomas, 22 schwannomas, 10 primary brain lymphomas in immunocompetent patients, and 5 bone tumors of the skull. The only tumors found to contain p53 mutations were 3 malignant lymphomas. The presence of mutations in these cases was confirmed by DNA sequencing. Given the high accuracy and sensitivity of the yeast assay and previous negative results using conventional techniques, this indicates that p53 mutation is a rare event in non-astrocytic CNS tumor types examined here.
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  • 36
    ISSN: 1432-0533
    Keywords: Key words Cytochrome c oxidase ; Fibre type ; Human ; Immunohistochemistry ; Myalgia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Muscular changes in male forest machine operators with work-related neck and shoulder myalgia were studied. Enzyme cyto- and immunohistochemical analysis was carried on muscle biopsies obtained from ten myalgic subjects (M), nine non-myalgic selected in the same work place (NM) and six healthy young men (C). The M group displayed a significant increase in type IIA fibres in comparison to the C group. This hypertrophy was accompanied by a parallel increase in the capillary bed. Both the M and NM groups exhibited an increase in fibres with a disorganised mitochondrial pattern. Interestingly, fibres lacking cytochrome c oxidase occurred in the M group (0.9%) but also in the NM group (0.5%), suggesting a mitochondrial defect. Central nuclei (5.2%) and developmental myosin (3%) were also more frequent in the M group. These changes are probably related to injury-regeneration cycles. These data support the association between the work conditions and muscle changes in work-related trapezius myalgia.
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  • 37
    ISSN: 1432-0533
    Keywords: Key words Focal ischemia ; Protein synthesis ; Substantia nigra ; Thalamus ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Following focal cerebral ischemia, neuronal cell death is detected in remote areas of the brain, including the ipsilateral thalamus and substantia nigra (SN), as well as in the ischemic core. We have investigated protein synthesis in the remote areas of rats exposed to focal ischemia using autoradiography. The proximal portion of the left middle cerebral artery (MCA) was permanently occluded, and at various periods (6 h, 2, 4 and 7 days and 2 and 4 weeks following ischemia) animals received a single dose of l-[2,3-3H]valine (6.7 mCi/kg). Brain sections containing the thalamus and SN were processed for autoradiography. In the ipsilateral cerebral cortex and striatum, marked impairment of protein synthesis was observed and was never completely recovered during the experiment. No changes in protein synthesis in the ipsilateral thalamus were detected during the experiment. However, a change in protein synthesis was demonstrated in the ipsilateral SN. At 2 days after MCA occlusion, incorporation of [3H]valine into the whole zona reticulata of the ipsilateral SN was slightly enhanced and the increase became evident at 4 days after ischemia. Increased incorporation of [3H]valine began to be localized in the lateral portion of the zona reticulata after 7 days and continued up to 4 weeks following ischemia. Enhanced protein synthesis during the early stage (2 and 4 days after ischemia) may be due to the activated function of the neurons in the zona reticulata and that during the late stage (7 days and 2 and 4 weeks) after ischemia to astroglial proliferation
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  • 38
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    Anatomy and embryology 197 (1998), S. 439-450 
    ISSN: 1432-0568
    Keywords: Key words Meckel’s cartilage ; Chondrocyte ; Transformation ; Resorption ; Apoptosis ; Mouse ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  It is unknown whether cells in the midportion of Meckel’s cartilage undergo transformation into other kinds of cell or whether resorption of cells occurs during development. Therefore, the midportion of Meckel’s cartilage from the mouse and the rat was subdivided into anterior and posterior portions. The ultimate fates of these tissues were analyzed with a focus on resorption-related cells, death of chondrocytes by apoptosis, and transformation of the chondrocytes themselves. Cellular and extracellular features of mouse Meckel’s cartilage were observed after von Kossa’s staining and staining for acid phosphatase (APase) activity, as well as by light and electron microscopy. To identify resorbing cells, immunostaining specific for macrophages and staining for tartrate-resistant acid phosphatase (TRAP) were performed. The DNA nick end-labeling (TUNEL) method was used for the detection of death of chondrocytes by apoptosis. The replacement of the extracellular matrix of rat Meckel’s cartilage was examined with double immunofluorescence staining for type I and type II collagens. When the anterior midportion from embryonic mice on day 18 was examined after von Kossa’s staining, it was clear that the extracellular matrix had already calcified and vascularization had been initiated that reflected the calcified matrix. TRAP staining and immunostaining for macrophages revealed two types of osteoclast and macrophages that were involved in resorption of the matrix. In the posterior midportion, no vascular invasion was evident, and chondrocytes were transformed directly into fibroblastic cells by phenotypic conversion. In such cells we found reaction products specific for APase activity, suggestive of the intracellular degradation of fine collagenous fibrils. Double immunofluorescence staining showed that cartilage-specific type II collagen was replaced by type I collagen with the phenotypic transformation to fibroblastic cells. There were no significant changes in the number of TUNEL-positive apoptotic cells from day 17 of gestation to day 6 after parturition. Death of chondrocytes by apoptosis was not, therefore, involved directly in the disappearance of Meckel’s cartilage. These results in the posterior midportion served as an instance of phenotypic switches in differentiated cells from chondrocytes to fibroblast-like cells. The present study indicates that there is a difference between the ultimate fate of cells in the posterior part and that of cells in the anterior part in the midportion of Meckel’s cartilage in the mouse and rat.
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  • 39
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    Surgical and radiologic anatomy 20 (1998), S. 185-189 
    ISSN: 1279-8517
    Keywords: Lateral pterygoid muscle ; Masticatory muscles ; Innervation ; Human ; Anatomy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé L'organisation du muscle ptérygoïdien latéral (LPM) en un ou deux chefs a été analysée à travers l'étude de son innervation. Tous les muscles étudiés présentaient une innervation provenant directement du tronc terminal antérieur du nerf mandibulaire. Cette innervation était issue de 1 à 3 nerfs ptérygoïdiens qui se divisaient rapidement en 2 à 8 branches principales. A l'intérieur du muscle, les nerfs s'organisaient en plans verticaux, parallèles entre eux, de dehors en dedans. Ils émettaient des rameaux terminaux horizontaux parallèles aux fibres musculaires. Ce muscle apparaissait donc divisé par des plans nerveux sagittaux obliques et horizontaux, ces derniers reflétant son organisation penniforme. Les couches musculaires pourraient être sélectivement recrutées lors des mouvements mandibulaires. L'organisation nerveuse intra-musculaire montre que le muscle ptérygoïdien latéral doit être considéré comme un muscle constitué d'une seule entité anatomique formée par une alternance de couches musculo-aponévrotiques fonctionnellement indépendantes.
    Notes: Summary The one- or two-headed arrangement of the lateral pterygoid m. (LPM) was analysed by studying the motor nerve distribution within the muscular tissue. In all subjects, the main innervation of the lateral pterygoid m. came from the anterior trunk of the mandibular n. by one to three nerves. These nerves divided into five or six vertical branches which ramified into parallel horizontal tiny fibers. Consequently, the lateral pterygoid m. appeared to be divided into oblique sagittal planes and horizontal layers by the nerve branches, reflecting the multipennate organisation of the muscle. These layers can be selectively recruited during mandibular movements, ensuing a fine medial-lateral control. According to its nerve supply, the LPM has to be considered as a single unit made of independent functional musulo-aponeurotic layers even though its morphologic conformation is in one, two or three heads.
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  • 40
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    Zeitschrift für Lebensmittel-Untersuchung und -Forschung 206 (1998), S. 393-398 
    ISSN: 1431-4630
    Keywords: Key words Dietary fibre ; Sugar beet pulp ; Biochemical parameters ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Process Engineering, Biotechnology, Nutrition Technology
    Notes: Abstract  Groups of 15 male rats were fed ad libitum for 4 weeks with a standard diet containing 0, 2.5, 5.0 or 10.0% dietary fibre (DF) prepared from sugar beet. The highest food consumption was found in the group with 10% DF in the diet. Food efficiency was highest in the control group. Average body weight increased continuously in all groups without significant differences. Enrichment of the diet with the DF preparation did not substantially influence urinary parameters [pH, specific gravity, protein or activities of aspartate aminotransferase (ASAT), alanine aminopeptidase and alkaline phosphatase (AP)]. Haemoglobin concentration and haematocrit, mean corpuscular haemoglobin concentration and mean corpuscular volume as well as total numbers of erythrocytes, thrombocytes and leukocytes counts did not significantly differ between the groups. Lower counts of eosinophils and neutrophils were measured in rats fed DF-enriched diets. Serum parameters (urea-N, protein, glucose, triglycerides and activities of ASAT, alanine aminotransferase, AP and leucine aminopeptidase) did not differ between groups. As the amount of DF preparation in the diet increased, serum cholesterol was reduced in trend. Furthermore, no significant differences were found between the groups with respect to the organ weights of rats. In conclusion, important or critical dose-related differences in the determined parameters were not found. This sub-acute feeding study showed that no toxic effects were related to used doses of DF which was prepared from sugar beet.
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  • 41
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    Zeitschrift für Lebensmittel-Untersuchung und -Forschung 207 (1998), S. 66-73 
    ISSN: 1431-4630
    Keywords: Key words Dietary fibre ; Sugar beet pulp ; Composition ; Fermentation ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Process Engineering, Biotechnology, Nutrition Technology
    Notes: Abstract  Groups of 15 female rats were fed ad libitum for 4 weeks with a standard diet containing 0, 2.5, 5 or 10% of a dietary fibre (DF) preparation made on a laboratory scale from sugar beet pulp. This preparation had a total DF content of 72.2%. Its major components were 36.7% cellulose, 16.9% pectin, 16.8% hemicelluloses (HC) and 11.0% protein. The DF preparation from sugar beet exhibited a water-binding capacity (WBC) of 8.9 g H2O/g. As the proportion of DF preparation in the diet increased, up to 15.8% total DF, 4.6% cellulose and 1.9% pectin were found in the feeds. The WBC of the diets was estimated to be 1.4–2.9 g H2O/g. At the end of the experiment, 20.3–64.1% total DF, 10.3–38.2% cellulose, 0.2–7.8% pectin, 4.3–9.2% HC pentoses and 4.3–10.3% HC hexoses were determined in caecum contents (ca. 0.6 g dry weight/rat). The following proportions were found in faeces (3rd week; 1.4–1.9 g dry weight/rat): 34.5–56.9% total DF, 19.5–36.1% cellulose, 6.4–8.4% HC pentoses, 7.4–8.3% HC hexoses. The WBC of faeces ranged from 3.7 g H2O/g to 4.9 g H2O/g. About 30–50% of the daily intake of DF appeared in the faeces. Higher amounts of total DF, pectin and HC pentoses were fermented by gastrointestinal microflora as the concentration of DF preparation from sugar beet in the diet increased. In addition, the fermentation of different DF components could be shown by the monosaccharide composition of caecum contents and faeces.
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  • 42
    ISSN: 1432-1211
    Keywords: Key words CD1 ; Rat ; Gene ; Organization ; Polymorphism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  The non-major histocompatibility complex (MHC)-encoded CD1 family has recently emerged as a new antigen-presenting system that is distinct from either MHC class I or class II molecules. In the present study, we determined the genomic structure of the rat CD1 locus. It was extremely similar to mouse CD1 genes, especially to CD1D1. The 5′ flanking region of the CD1 gene contained the binding motifs for two cytokine-inducible transcription factors, NF-IL2-A and NF-IL6. Some regulatory elements found in MHC class I genes (enhancer A, enhancer B, and the IFN response element) were absent. It is of interest that a tyrosine-based motif for endosomal localization found in the human CD1b cytoplasmic tail was encoded by a single short exon which was conserved in all CD1 molecules except for CD1a. Southern blot and direct sequencing analyses of inbred rat strains suggested very limited polymorphism in the 5′ region where a hydrophobic ligand-binding groove is encoded; a single base substitution resulted in amino acid alteration of alanine (GCT) to valine (GTT) at codon 119. Comparison of the overall exon-intron organization of CD1 genes revealed that the length of the intron was also characteristic to each of the two classes of CD1 genes, classic CD1 and CD1D; such categorization has hitherto been made according to the sequence similarity of the coding region. This finding provides further support for the hypothesis that the two classes have different evolutionary histories. In contrast to the complete absence of the classic CD1 in rats and mice, the entire region of nonpolymorphic CD1D has been conserved through mammalian evolution. Similar functional properties of rodent CD1 and human CD1d are implied.
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  • 43
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    Immunogenetics 48 (1998), S. 40-46 
    ISSN: 1432-1211
    Keywords: Key words Immunoglobulin ; Genes ; Kappa light chain ; Human ; Antibody repertoire
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  We describe a hitherto unknown functional IGKV gene, VkLa, belonging to the IGKV1 subgroup with exon 2 having only 94% similarity to the closest known IGKV gene, 1–13/1D-13 (L4/L18a). Genomic DNA sequences spanning from 5’ of the decanucleotide box to 3’ of the heptamer (649 bp) were cloned and sequenced from four individuals. The new gene encodes the conserved amino acids in the exons and contains no apparent defects in known regulatory intron sequences such as pd-box, dc-box, TATA-box, CCCT-elements, splice-sequences, initiation codon, and heptamer sequence. VkLa is therefore potentially functional and, correspondingly, we found transcripts of properly rearranged VkLa with somatical hypermutations. VkLa was found in 12 of 57 (21%) healthy Caucasians by a nested polymerase chain reaction and subsequent sequencing of exon 2. This finding shows that there is more inter-individual variation in the available IGKV gene repertoire than was hitherto assumed. Finally, we describe a minor correction in the IGKV1D-43 (L23) gene sequence.
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  • 44
    ISSN: 1432-1211
    Keywords: Key words Antigen presenting cells ; Dendritic cells ; Cell surface molecule ; Antigen receptor ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  Dendritic cells (DC) are specialist antigen presenting cells which capture antigens in the periphery, migrate centrally, and present the processed antigens in the context of major histocompatibility complex and appropriate co-stimulatory molecules to T lymphocytes for the initiation of an immune response. DEC-205 has been identified as a putative antigen-uptake receptor, which is expressed abundantly on mouse DC. The recently cloned mouse DEC-205 cDNA predicts a molecular structure which has a marked similarity to the macrophage mannose receptor. Using reverse transcriptase-polymerase chain reaction (RT-PCR) and cDNA library screening, we obtained the full coding region of human DEC-205 cDNA from the Hodgkin’s disease-derived L428 cell line. The predicted protein structure is a type I transmembrane protein of 1722 amino acids consisting of a signal peptide, cysteine-rich domain, fibronectin type II domain, ten carbohydrate recognition-like domains, transmembrane domain, and a cytoplasmic tail. Human DEC-205 is 77% identical to the mouse protein with completely conserved cysteines. The DEC-205 gene (LY75) was mapped to chromosome band 2q24 by somatic cell hybrid panel analysis and fluorescent in situ hybridization. Northern blot analysis detected 7.8 and 9.5 kilobase DEC-205 transcripts in myeloid, B lymphoid, and Hodgkin’s disease-derived cell lines. RT-PCR analysis indicated that immature blood DC contain a barely detectable amount of DEC-205 transcripts but these were markedly increased upon differentiation/activation.
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  • 45
    ISSN: 1432-1211
    Keywords: Key words RT1.S3 ; Grc ; MHC ; Class I ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
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  • 46
    ISSN: 1432-1238
    Keywords: Key words Intensive care ; Critical care ; Intensive care unit/organization and administration ; Respiration ; artificial/method ; Human ; Organizational policy ; Data collection ; Health care survey ; Questionnaire ; Length of stay
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Objective: To determine whether there is variability in the structure and process of ventilatory care in intensive care units (ICUs) of the hospitals of Southwestern Ontario. Design: Self-administered questionnaire-based survey. Setting: ICUs of selected community and teaching hospitals of Southwestern Ontario. Participants: Head of respiratory therapy service of respective hospitals; in those hospitals without respiratory therapists, the ICU nurse manager. Intervention: Self-administered questionnaire. Outcome measure(s): The availability of different models of ventilators and respiratory therapist and physician coverage were assessed. In addition, the use of clinical practice guidelines, respiratory therapists, and the nursing role in ventilatory care were determined. Results: In general, the structure of ventilatory care, including availability of different modes of ventilation, and coverage by respiratory therapists and physicians was more comprehensive in larger hospitals. However, the availability of some modes of ventilation varied more than expected among hospitals of comparable size. Similarly, variability in the process of ventilatory care, defined by the availability of clinical practice guidelines and the roles of respiratory therapists varied both within and among hospitals of different size. Conclusions: The structure and process of ventilatory care in this sample of Southwestern Ontario ICUs was found to be variable. Not all this variability could be accounted for by hospital size, suggesting a potential for improvement in overall ventilatory care. Further study is required before any specific recommendations can be considered.
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  • 47
    ISSN: 1432-1238
    Keywords: Key wordsK. pneumoniae ; Bacteremia ; Mechanical ventilation ; Blood gases ; Animal ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Objective: To determine the effect of peak inspiratory pressure (PIP) and positive end-expiratory pressure (PEEP) on the development of bacteremia with Klebsiella pneumoniae after mechanical ventilation of intratracheally inoculated rats. Design: Prospective, randomized, animal study. Setting: Experimental intensive care unit of a University. Subjects: Eighty male Sprague Dawley rats. Interventions: Intratracheal inoculation with 100 μl of saline containing 3.5–5.0 × 105 colony forming units (CFUs) K. pneumoniae/ml. Pressure-controlled ventilation (frequency 30 bpm; I/E ratio = 1 : 2; FIO2 = 1.0) for 180 min at the following settings (PIP/PEEP in cmH2O): 13/3 (n = 16); 13/0 (n = 16); 30/10 (n = 16) and 30/0 (n = 16), starting 22 h after inoculation. Arterial blood samples were obtained and cultured before and 180 min after mechanical ventilation and immediately before sacrifice in two groups of non-ventilated control animals (n = 8 per group). After sacrifice, the lungs were homogenized to determine the number of CFUs K. pneumoniae. Measurements and results: The number of CFUs recovered from the lungs was comparable in all experimental groups. After 180 min, 11 animals had positive blood cultures for K. pneumoniae in group 30/0, whereas only 2, 0 and 2 animals were positive in 13/3, 13/0 and 30/10, respectively (p 〈 0.05 group 30/0 versus all other groups). Conclusions: These data show that 3 h of mechanical ventilation with a PIP of 30 cmH2O without PEEP in rats promotes bacteremia with K. pneumoniae. The use of 10 cmH2O PEEP at such PIP reduces ventilation-induced K. pneumoniae bacteremia.
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  • 48
    ISSN: 1432-1238
    Keywords: Key words Hepatocyte growth factor (HGF) ; Pneumonectomy ; Lung growth ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Objective: Proliferation of alveolar type II cells is thought to be critical for the restoration of lung function after diffuse alveolar damage or pneumonectomy. However, the factors that regulate alveolar type II cell proliferation, and the mechanism that brings about compensatory lung growth are not well understood. Hepatocyte growth factor (HGF) has been shown to have hepatotrophic and nephrotrophic functions for regeneration of the liver and kidney. We have attempted to investigate the involvement of HGF in lung regeneration after lung resection. Desgin: A prospective, controlled study. Setting: Adult surgical patients in a university hospital. Patients and measurements: We measured serum HGF levels in eight patients undergoing major lung resection, and in five patients undergoing mastectomy as controls, by using radioimmunoassay and an enzyme-linked immunosorbent assay. Results: In all cases of pneumonectomy, the serum HGF levels increased 3- to 5-fold at 1–3 days (with a peak at 3 days) after operation, and then decreased to nearly basal levels in 2 weeks. However, these levels in patients undergoing mastectomy did not change much over the first 2 weeks, postoperatively. Conclusions: Serum HGF levels increased in patients after major lung resection, which suggests that HGF might play an important role in lung regeneration or compensatory lung growth in humans.
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  • 49
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    International journal of biometeorology 42 (1998), S. 84-88 
    ISSN: 1432-1254
    Keywords: Key words Mortality ; Human ; Seasonality ; Secular trend ; Temperature
    Source: Springer Online Journal Archives 1860-2000
    Topics: Geography , Physics
    Notes: Abstract  Based on records from the Federal Bureau for Statistics of Germany, the seasonality of mortality was investigated for the period 1946–1995. Lowest mortality rates were found during summer (August or September) while highest values were found in winter (January through March). Non-linear regression of all monthly mortality data with the average monthly temperatures in Germany revealed a significant negative relationship (r=–0.739; n=600; P〈0.0001). The fact that the differences between the long-range monthly temperatures and the individual monthly temperatures also showed a distinct relationship to the mortality rates speaks against a mere coincidence of both parameters. The amplitude of this seasonal rhythm declined steadily within the observation period. It is concluded that low temperatures cause an increase in mortality rates and that this effect has become less important during recent decades due to the increased use of central heating and because of improvements in the public health system.
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  • 50
    ISSN: 1432-1335
    Keywords: Key words Small-intestine phenotype ; Sucrase ; Intestinal-type alkaline phosphatase ; Colon cancer ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In this study the small-intestine phenotype in rat colonic tumors was investigated in terms of sucrase and intestinal-type alkaline phosphatase (I-ALP) activity. F344 rats were given intraperitoneal injections of methylazoxymethanol acetate at a dose level of 25 mg/kg body weight once a week for 8 weeks and were killed 40 weeks after the first injection. Sucrase and I-ALP activities in proximal and distal colon adenocarcinomas were significantly higher than those in the normal colon epithelium. In the jejunum, by contrast, normal tissue had significantly higher levels than tumors. Immunohistochemical staining of I-ALP was also strong in striated cell borders of colon adenocarcinoma cells. These data suggest that, whereas absorptive cells of the small intestine lose their own traits with tumor development, colonocytes acquire phenotypic features of the small intestine. Intestinal enzymes associated with the striated-cell border, such as sucrase and I-ALP, may be useful markers for malignant phenotypic expression in colonocytes.
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  • 51
    ISSN: 1432-1106
    Keywords: Key words Cerebellar patients ; Double-step paradigm ; Pointing movement ; Kinematic analysis ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Three patients with cerebellar limb ataxia and three age-matched controls performed arm-pointing movements towards a visual stimulus during an experimental procedure using a double-step paradigm in a three-dimensional space. Four types of trajectories were defined: P1, single-step pointing movement towards the visual stimulus in the initial position S1; P2, double-step pointing movement towards S1; P3, double-step straight pointing movement towards the second position S2; and P4, double-step pointing movement towards S2 with an initial direction towards S1. We found that the cerebellar patients, as well as the controls, were able to modify their motor programs, but with impaired timing, severe anomalies in the direction and amplitude of the changed movement trajectories and alteration of the precision of the pointing movements.
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  • 52
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    Experimental brain research 119 (1998), S. 467-474 
    ISSN: 1432-1106
    Keywords: Key words Aging ; Feedback ; Vision ; Program control ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Young and elderly subjects performed aiming movements to a visual target with a manipulandum to determine whether the elderly reduce their reliance on visual feedback after extended practice. Reliance on visual feedback was assessed by performance on trials in which the cursor displaying arm movement was unpredictably extinguished. Movements were divided into two subcomponents: a primary, ballistic submovement and a secondary, corrective submovement. For both age groups, removal of visual feedback prior to practice resulted in a decrease in the distance covered in the primary submovement, an increase in the distance of the secondary submovement, and a decrease in endpoint accuracy. After extensive practice with the cursor present, the proportion of distance traveled with the primary submovement was again assessed under trial conditions in which the cursor randomly disappeared. Following practice, the young demonstrated that they were capable of extending the primary submovement distance closer to the target. In addition, primary submovement distance was unaffected by the removal of vision following practice. After practice the elderly did not show evidence of lengthening the primary submovement, and submovement distance and endpoint accuracy continued to be altered by the removal of vision. This suggests that, unlike the young, the elderly do not benefit from practice so that they can place a greater proportion of the movement under program control. Thus, on a relative basis, a greater proportion of their overall movement requires corrective adjustments.
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  • 53
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    Experimental brain research 119 (1998), S. 475-482 
    ISSN: 1432-1106
    Keywords: Key words Proprioception ; Eye position ; Botulinum toxin ; Strabismus ; Palisade ending ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Botulinum toxin is sometimes injected into human eye muscles as an alternative to surgery in the correction of strabismus. Within minutes of botulinum injections into ungulate eye muscles, proprioceptive discharge from muscle spindles decreases dramatically. It is only over 7–48 h, however, that surgically treated strabismus patients usually show an altered proprioceptive signal about eye position, presumably from the palisade endings attached to the global multiply innervated fibers. How quickly will botulinum toxin alter proprioceptive registration of eye position in humans? First, to examine the short-term effects, we measured open-loop pointing responses (which requires knowledge of eye position) in six strabismus patients preinjection and then over a 45 min postinjection period, and in six normal controls over the same time period. Second, to examine the long-term effects, 13 strabismus patients were tested preinjection and then daily over the next 3 weeks, and three normal controls over the same time period. We compared their open-loop pointing responses with the injected eye fixating the target to the photographically determined position of the occluded other eye (a measure of where the patient would point if eye position were determined by efference, not proprioception). There were three groups of patients: esotropes with no previous injection, exotropes with no previous injection, and exotropes with previous injection. First, all patients showed significant correction of their tropias. Second, over the short-term, there was no difference in pointing responses found between the patients and the controls (t(18) = –1.427, P = 0.1706). Third, over the long-term, however, the difference between the pointing responses and eye position information was compared among the four groups across four posttests and a significant difference found (F 3,12 = 58.988, P 〈 0.00001). Only in patients with no previous injections was there altered proprioceptive feedback about eye position. Also, injections into the medial rectus induced a significantly greater proprioceptive response than those injected into the lateral rectus. In humans, botulinum toxin alters proprioception from eye muscles only over the long-term. We suggest that the toxin temporarily affects proprioceptive feedback from palisade endings.
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  • 54
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    Experimental brain research 119 (1998), S. 483-492 
    ISSN: 1432-1106
    Keywords: Key words Cerebellar ataxia ; Limb movement ; Multijoint movement ; Kinematics ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Kinematic abnormalities of fast multijoint movements in cerebellar ataxia include abnormally increased curvature of hand trajectories and an increased hand path and are thought to originate from an impairment in generating appropriate levels of muscle torques to support normal coordination between shoulder and elbow joints. Such a mechanism predicts that kinematic abnormalities are pronounced when fast movements are performed and large muscular torques are required. Experimental evidence that systematically explores the effects of increasing movement velocities on movement kinematics in cerebellar multijoint movements is limited and to some extent contradictory. We, therefore, investigated angular and hand kinematics of natural multijoint pointing movements in patients with cerebellar degenerative disorders and healthy controls. Subjects performed self-paced vertical pointing movements with their right arms at three different target velocities. Limb movements were recorded in three-dimensional space using a two-camera infrared tracking system. Differences between patients and healthy subjects were most prominent when the subjects performed fast movements. Peak hand acceleration and deceleration were similar to normals during slow and moderate velocity movements but were smaller for fast movements. While altering movement velocities had little or no effect on the length of the hand path and angular motion of elbow and shoulder joints in normal subjects, the patients exhibited overshooting motions (hypermetria) of the hand and at both joints as movement velocity increased. Hypermetria at one joint always accompanied hypermetria at the neighboring joint. Peak elbow angular deceleration was markedly delayed in patients compared with normals. Other temporal movement variables such as the relative timing of shoulder and elbow joint motion onsets were normal in patients. Kinematic abnormalities of multijoint arm movements in cerebellar ataxia include hypermetria at both the elbow and the shoulder joint and, as a consequence, irregular and enlarged paths of the hand, and they are marked with fast but not with slow movements. Our findings suggest that kinematic movement abnormalities that characterize cerebellar limb ataxia are related to an impairment in scaling movement variables such as joint acceleration and deceleration normally with movement speed. Most likely, increased hand paths and decomposition of movement during slow movements, as described earlier, result from compensatory mechanisms the patients may employ if maximum movement accuracy is required.
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  • 55
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    Experimental brain research 119 (1998), S. 504-510 
    ISSN: 1432-1106
    Keywords: Key words Clicks ; Galvanic stimulation ; Vestibular reflexes ; Vestibulospinal reflexes ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The aim of this study was to demonstrate, if possible, vestibulospinal reflex responses in soleus using a stimulus known to be capable of exciting vestibular afferents, namely 100-dB (NHL) clicks. We were able to show short-latency electromyographic (EMG) responses after clicks in five of eight normal subjects, and then we compared these responses with those after transmastoid galvanic stimulation (12 normal subjects). Stimulation of the side towards which the head was rotated (i.e. the side facing backwards) with either clicks or the cathode (anode applied to the opposite side) gave an initial excitatory response in soleus, while click or cathodal stimulation of the opposite side (i.e. the side facing forwards) gave an initial inhibitory response. Onset latencies and modulation with changes in postural task were identical for both click- and galvanic-evoked responses. In addition, there was a significant correlation between the amplitudes of the responses in soleus after click and galvanic stimulation (R 2=0.72). These similarities suggest that the earliest reflex responses in soleus after clicks and galvanic stimulation may be mediated by a common central pathway. In contrast, there was no correlation between the amplitudes of responses evoked by 100-dB clicks in soleus and those evoked by the same stimulus in the sternocleidomastoid. We conclude that vestibular activation by clicks can evoke reflex responses in lower-limb muscles and these responses have similar characteristics to the earliest responses evoked by galvanic vestibular stimulation.
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  • 56
    ISSN: 1432-1106
    Keywords: Key words Cerebellar ataxia ; Limb movements ; Dynamics ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  In cerebellar ataxia, kinematic aberrations of multijoint movements are thought to originate from deficiencies in generating muscular torques that are adequate to control the mechanical consequences of dynamic interaction forces. At this point the exact mechanisms that lead to an abnormal control of interaction torques are not known. In principle, the generation of inadequate muscular torques may result from an impairment in generating sufficient levels of torques or from an inaccurate assessment and prediction of the mechanical consequences of movements of one limb segment on adjacent joints. We sought to differentiate the relative contribution of these two mechanisms and, therefore, analyzed intersegmental dynamics of multijoint pointing movements in healthy subjects and in patients with cerebellar degeneration. Unrestrained vertical arm movements were performed at three different target movement velocities and recorded using an optoelectronic tracking system. An inverse dynamics approach was employed to compute net joint torques, muscular torques, dynamic interaction torques and gravitational torques acting at the elbow and shoulder joint. In both groups, peak dynamic interaction forces and peak muscular forces were largest during fast movements. In contrast to normal subjects, patients produced hypermetric movements when executing fast movements. Hypermetric movements were associated with smaller peak muscular torques and smaller rates of torque change at elbow and shoulder joints. The patients’ deficit in generating appropriate levels of muscular force were prominent during two different phases of the pointing movement. Peak muscular forces at the elbow were reduced during the initial phase of the movement when simultaneous shoulder joint flexion generated an extensor influence upon the elbow joint. When attempting to terminate the movement, gravitational and dynamic interaction forces caused overshooting extension at the elbow joint. In normal subjects, muscular torque patterns at shoulder and elbow joint were synchronized in that peak flexor and extensor muscular torques occurred simultaneously at both joints. This temporal pattern of muscular torque generation at shoulder and elbow joint was preserved in patients. Our data suggest that an impairment in generating sufficient levels of phasic muscular torques significantly contributes to the patients’ difficulties in controlling the mechanical consequences of dynamic interaction forces during multijoint movements.
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  • 57
    ISSN: 1432-1106
    Keywords: Key words Central pain ; Endogenous opioids ; Naloxone ; Neuropathic pain ; Spinal cord ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  We have previously reported that ischemic spinal cord injury in rats leads to chronic pain-related behaviors. Thus, rats exhibited aversive reactions to innocuous mechanical stimuli (mechanical allodynia) applied to a body area at or rostral to the dermatomes innervated by the injured spinal segments. The responses of the rats to cold are also markedly enhanced (cold allodynia). Interestingly, more than 50% of spinally injured rats did not develop these abnormal pain-related behaviors after spinal cord injury. In the present study, we showed that the extent of injury is similar between allodynic and nonallodynic rats. Furthermore, intrathecal (i.t.) naloxone, a broad-spectrum opioid receptor antagonist, reversibly provoked mechanical and cold allodynia-like responses in spinally injured rats that did not develop such behaviors spontaneously. However, naloxone did not elicit such reactions in normal rats and did not alter the tail-flick latency in normal or spinally injured rats. Furthermore, i.t. d-Phe-Cys-Tyr-d-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP) or naltridole, selective antagonists of μ and δ opioid receptors, respectively, also triggered pain-related behaviors similarly to naloxone. Although norbinaltorphimine (nor-BIN), a selective κ-receptor antagonist, also elicited such responses, the time course of the effect makes it unlikely that spinal κ-receptors were involved. These results suggested that the expression of abnormal pain-related behaviors in some spinally injured rats is tonically suppressed by the spinal opioidergic system. Interindividual differences that lead to lack or dysfunction of such inhibition may underly the appearence of pain-related behavior in some, but not all, spinally injured rats. It is suggested that such inhibition is exerted through spinal μ and δ, but not κ, opioid receptors. The endogenous opioidergic control appears to be only active against abnormal pain-related behaviors in spinally injured rats. Our results are relevant for the clinical observation that only a subgroup of patients with nerve injury suffers from neuropathic pain.
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  • 58
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    Experimental brain research 118 (1998), S. 352-360 
    ISSN: 1432-1106
    Keywords: Key words Attention ; Inhibition of return ; Crossmodal ; Orienting ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  It is currently controversial whether auditory events produce inhibition of return (IOR). Although some authors argue that this can arise, others propose that peripheral auditory cues do not produce the characteristic IOR pattern of delayed detection latencies for ipsilaterally presented auditory or visual targets, unless a saccade is made to the cued location. We suggest that these previous discrepancies may depend on whether attention is reoriented centrally following the peripheral sound. We presented spatially uninformative peripheral auditory cues prior to visual targets requiring speeded detection responses. IOR was found in the absence of eye movements, provided an auditory reorienting event was presented at central fixation between onset of the peripheral cue and the subsequent target, but not when the central reorienting event was visual. A subsequent experiment demonstrated that auditory IOR between successive targets is similarly significantly reduced in the absence of an appropriate central reorienting event. These results imply that auditory stimuli can induce IOR directly. Previous failures to demonstrate IOR following auditory cues may have been due to an opposing influence of long-lasting attentional facilitation at the cued location, rather than to the putative inability of auditory stimuli to engage oculomotor processes generating IOR.
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  • 59
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    Experimental brain research 118 (1998), S. 361-372 
    ISSN: 1432-1106
    Keywords: Key words Noradrenaline ; Neuromodulator ; Iontophoresis ; Intensity function ; Threshold ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  To test a potential “gating” effect of noradrenaline (NA) in the auditory cortex, the acoustic threshold was estimated by determining the rate-level function of neurons before, during, and after microiontophoretic application (5–40 nA) of NA. The rationale behind this experiment was that a gating effect should decrease the threshold for acoustic excitatory responses. From 84 recorded neurons, we observed (1) that application of NA increased the threshold for 48 of 84 cells, and (2) that, on average, the slope of the rate-level functions was unchanged. These effects on the threshold are consistent with the fact that the dominant effect of NA on the evoked response is inhibition for 34 of 84 cells; increases in evoked responses were observed for only 14 of 84 cells. GABA application (0–50 nA) also led to increased response threshold for 19 of 24 cells (unaffected, 5 of 24 cells). However, for three cells the effect of GABA application was antagonized by bicuculline application, while on the same cells bicuculline application did not prevent the noradrenergic increase in threshold. The effect induced by NA on the threshold raises questions about the generality of a gating effect of NA in sensory neocortex.
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  • 60
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    Experimental brain research 118 (1998), S. 415-420 
    ISSN: 1432-1106
    Keywords: Key words Vergence ; Depth perception ; Proprioception ; Limb position ; Pointing ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  We sought to determine whether an increase in judged egocentric distance created by increasing vergence-specified distance would be negated when participants pointed at their own finger. It was found that ocular position dominates limb proprioception in the judgement of finger distance in the sagittal plane when vision is available. In contrast, an increase in perceived egocentric distance was largely attenuated by the presence of limb proprioception in reduced visual cue conditions. We conclude that the relative contribution of vergence to perceived distance depends upon the strength of the vergence effort signal when there are other cues present. Furthermore, if the distance percept includes a major contribution from retinal cues, then the visual component will dominate the limb proprioception component. If the visual component is largely determined by vergence information, limb proprioception will make a significant contribution and actually dominate when the vergence effort signal is weak. The results extend previous studies that have found a similar relationship between ocular position and limb proprioception in the perception of a finger′s location in the coronal plane.
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  • 61
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    Experimental brain research 118 (1998), S. 408-414 
    ISSN: 1432-1106
    Keywords: Key words Visual perception ; Visuomotor control ; Orientation ; Depth ; Binocular vision ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Normal human subjects were tested for their ability to discriminate the orientation of a square plaque tilted in depth, using two different tasks: a grasping task and a perceptual matching task. Both tasks were given under separate monocular and binocular conditions. Accuracy of performance was measured by use of an opto-electronic motion analysis system, which computed the hand orientation (specifically, a line joining the tips of the thumb and index finger) as the hand either approached the target during grasping or was used to match the target. In all cases there was a very strong statistical coupling between hand orientation and target orientation, irrespective of viewing conditions. However, the matching data differed from the grasping data in showing a consistent curvature in the hand-target relationship, whereby the rate of change of hand orientation as a function of object orientation was smaller for oblique orientations than for those near the horizontal or vertical. The results are interpreted as reflecting the operation of two different mechanisms for analysing orientation in depth: a visuomotor system (assumed to be located primarily in the dorsal cortical visual stream) and a perceptual system (assumed to be located in the ventral stream). It may be that the requirements of visuomotor control dictate a primary need for absolute orientation coding, whereas those of perception dictate a need for more categorical coding.
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  • 62
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    Experimental brain research 118 (1998), S. 427-430 
    ISSN: 1432-1106
    Keywords: Key words H-reflex ; Interlimb coordination ; Voluntary movement ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  In 12 subjects, each sitting on an armchair with the right forearm prone, the H-reflex elicited in the resting flexor carpi radialis muscle underwent cyclic excitability changes correlated with rhythmic flexion-extension movements of the ipsilateral foot (frequency of oscillations between 1.5 and 2.5 Hz). During foot plantar flexion, the H-reflex underwent a clear-cut increase, the maximum facilitation falling, in most subjects, within the second half of that phase; then, a gradual reduction in size led the reflex amplitude back to the initial value at the end of foot dorsal extension. If present also when the wrist and the ankle are moved together, this facilitation should favour the in-phase (isodirectional) association between movements and, conversely, hinder the anti-phase coupling.
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  • 63
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    Experimental brain research 118 (1998), S. 421-426 
    ISSN: 1432-1106
    Keywords: Key words Intracortical inhibition ; Transcranial magnetic stimulation ; Motor exercise ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The motor-evoked potential (MEP) to transcranial magnetic stimulation (TMS) is inhibited when preceded by a subthreshold TMS stimulus at short intervals (1–6 ms; intracortical inhibition, ICI) and is facilitated when preceded by a subthreshold TMS at longer intervals (10–15 ms; intracortical facilitation, ICF). We studied changes in ICI and ICF associated with two motor tasks requiring a different selectivity in fine motor control of small hand muscles (abductor pollicis brevis muscle, APB, and fourth dorsal interosseous muscle, 4DIO). In experiment 1 (exp. 1), nine healthy subjects completed four sets (5 min duration each) of repetitive (1 Hz) thumb movements. In experiment 2 (exp. 2), the subjects produced the same number of thumb movements, but complete relaxation of 4DIO was demanded. Following free thumb movements (exp. 1), amplitudes of MEPs in response to both single and paired TMS showed a trend to increase with the number of exercise sets in both APB and 4DIO. By contrast, more focal, selective thumb movementsinvolving APB with relaxation of 4DIO (exp. 2) caused an increase in MEP amplitudes after single and paired pulses only in APB, while a marked decrease in MEPs after paired pulses, but not after single TMS, in the actively relaxed 4DIO. This effect was more prominent for the interstimulus interval (ISI) of 1–3 ms than for longer ISIs (8 ms, 10 ms, and 15 ms). F-wave amplitudes reflecting excitability of the alpha motoneuron pool were unaltered in APB and 4DIO, suggesting a supraspinal origin for the observed changes. We conclude that plastic changes of ICI and ICF within the hand representation vary according to the selective requirements of the motor program. Performance of more focal tasks may be associated with a decrease in ICI in muscles engaged in the training task, while at the same time ICI may be increased in an actively relaxed muscle, also required for a focal performance. Additionally, our data further supports the idea that ICI and ICF may be controlled independently.
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  • 64
    ISSN: 1432-1106
    Keywords: Key words Transcranial magnetic stimulation ; Interhemispheric transfer ; Simple reaction time ; Manual response ; Poffenberger paradigm ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  We investigated the cerebral cortical route by which visual information reaches motor cortex when visual signals are used for manual responses. Subjects responded unimanually to photic stimuli delivered to the hemifield ipsilateral or contralateral to the moving hand. On some trials, trans-cranial magnetic stimulation (TMS) was applied unilaterally over the occiput, with the aim of stimulating extrastriate visual areas and thereby modifying transmission of visual input. In association with the side of a visual stimulus and a motor response, TMS could change inter- or intra-hemispheric transmission needed to convey visual information to motor areas. Reaction time differences following TMS suggested that TMS exerted an inhibitory effect only when visuo-motor information had to be transferred interhemispherically. This result reinforces evidence for an extrastriate pathway of interhemispheric transfer of visuomotor information.
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  • 65
    ISSN: 1432-1106
    Keywords: Key words Posterior hypothalamus ; Histamine ; Memory ; Immunohistochemistry ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The tuberomammillary nucleus (TM) located in the posterior part of the hypothalamus is the main source of neuronal histamine in the central nervous system. Recent work from our laboratories has indicated an involvement of the TM region in neuronal plasticity and reinforcement processes. In the present study, we investigated the effects of TM lesions on the performance of adult and aged Wistar rats in a set of learning tasks, which differed in terms of complexity and reward contingencies (habituation learning, inhibitory avoidance, discrimination learning, Morris water maze). An improvement was found in every test applied, indicating that TM lesions seem to generally enhance learning and memory capacities independent of the special demands of a given task. Age-related learning deficits were strongly diminished. Immunohistochemistry revealed that the excitotoxic lesions used to destroy the TM region led to a marked decrease in the number of histamine-positive neurons in the vicinity of the injection site, indicating an involvement of the brain histaminergic system in the observed behavioral changes.
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  • 66
    ISSN: 1432-1106
    Keywords: Key words Extracellular recording ; Cortical efferents ; A10 cell group ; Non-dopaminergic neurons ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  It is rapidly becoming apparent that the prefrontal cortex (PFC) plays a major role in controlling the activity of midbrain dopaminergic (DA) neurons. We have previously demonstrated that electrical stimulation of the PFC elicits inhibition-excitation (IE) and excitation (E) activity patterns in DA neurons in the ventral tegmental area (VTA; A10 cell group). Since non-DA neurons in the VTA are cortically innervated, synapse upon DA neurons and appear to have an inhibitory impact, we determined the extent to which the responses of these neurons to stimulation of the PFC could account for the responses seen in DA neurons upon cortical stimulation. Stimulation of the PFC (0.25 mA and 1.0 mA) elicited three categories of response in the majority of VTA non-DA neurons. Types I and II were characterised by a short-to-moderate latency excitation (referred to as “early excitations”), in the latter case preceded by inhibition. Type III responses consisted of inhibition in the absence of an early excitation. Elements of these responses were compared with the temporal characteristics of key elements of responses elicited in DA neurons by PFC stimulation. Although the early excitations in non-DA neurons preceded the inhibitions in DA neurons exhibiting IE responses, the early excitations began approximately 100 ms before the inhibitions in DA neurons and often ended several tens of milliseconds before the inhibitions began, making a causal relationship between these events unlikely. The inhibitions in Type III responses, combined with the inhibitions which followed the early excitations in many Type I and II responses, showed temporal characteristics that suggested a possible causal relationship with the excitations in DA neurons exhibiting E responses, but not those exhibiting IE responses. However, since the excitatory phases of E and IE responses appear to be homologous, the lack of involvement of non-DA neurons in the excitatory phase of IE responses tends to cast doubt on the involvement of non-DA neurons in the excitation during E responses. In fact, the most coherent impression that emerges is that non-DA neurons in the VTA do not influence the activity of A10 DA neurons on a short time-scale (i.e. phasically), but instead may influence activity on a longer time-scale (i.e. tonically).
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  • 67
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    Experimental brain research 118 (1998), S. 477-488 
    ISSN: 1432-1106
    Keywords: Key words Visual cortex ; Brain slice ; Strength-duration relations ; Conduction velocity ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Extracellular electrical stimulation of the gray matter is often used to determine the function of a given cortical area or pathway. However, when it is used to elicit postsynaptic effects, the presynaptic neuronal elements activated by electrical stimulation have never been clearly identified: it could be the excitable dendrites, the cell body, the axon initial segment, or the axonal branches. To identify these elements, we performed two series of experiments on slices of rat visual cortex maintained in vitro. The first series of experiments, reported in this paper, was aimed at determining the chronaxie, a temporal parameter related to the membrane properties of the neuronal elements. In order to identify the presynaptic elements that were activated by extracellular electrical stimulation, chronaxies corresponding to postsynaptic responses were measured and compared with those corresponding to the activation of axons (antidromic activation) and those corresponding to the activation of cell bodies (intracellular current injection in intracellularly recorded neurons). The chronaxie for orthodromic activation was similar to that for axonal activation, but was 40 times smaller than the chronaxie for direct cell body activation. This suggests that, whenever a postsynaptic response is elicited after electrical stimulation of the cortical gray matter, axons (either axonal branches or axon initial segments), but not cell bodies, are the neuronal elements activated.
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  • 68
    ISSN: 1432-1106
    Keywords: Key words Visual cortex ; Brain slice ; Intracortical microstimulation ; NMDA ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The results presented in the companion paper showed that extracellular electrical stimulation of the gray matter directly activates axons, but not cell bodies. The second set of experiments presented here was designed to separate the contribution of the axon initial segments and cell bodies from that of the axonal branches to the pool of presynaptic neuronal elements activated by electrical stimulation. For that purpose, N-methyl-d-aspartate (NMDA) iontophoresis was used to induce a selective inactivation of the cell body and of the adjoining portion of the axon by depolarization block, without affecting axonal branches that lack NMDA receptors. After NMDA iontophoresis, the neurons located near the iontophoresis electrode became unable to generate action potentials in an irreversible manner. When the NMDA-induced depolarization block was performed at the site of electrical stimulation, an unexpected increase in the amplitude of the orthodromic responses was observed. Several control experiments suggested that the field potential increase was due to changes of the local environment in the vicinity of the iontophoresis pipette, which led to an increased excitability of the axons. After the period of superexcitability, the orthodromic responses displayed an amplitude that was 15—20% lower than that observed before the NMDA-induced depolarization block, even though cell bodies and axon initial segment at the site of stimulation could not be activated by electrical stimulation. This result shows a low contribution for axon initial segments to the pool of neuronal elements activated by the electrical stimulation. Altogether, these experiments demonstrate that the postsynaptic responses obtained after electrical stimulation of the cortical gray matter result almost exclusively from the activation of axonal branches. Since the neocortex is organised as a network of local and long-range reciprocal connections, great attention must be paid to the interpretation of data obtained with electrical stimualtion.
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  • 69
    ISSN: 1432-1106
    Keywords: Key words Thalamic reticular nucleus ; Learning ; Memory ; Two-way active avoidance ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Two experiments were performed in order to study the effects of lesions of the rostral thalamic reticular nucleus (Rt) on two-way active avoidance. Male wistar rats were subjected to either a bilateral electrolytical lesion of the rostral Rt or to control procedures. After recovery, all rats were trained in either a distributed (five training sessions, ten trials each; experiment I) or a massed (a single 30-trials session; experiment II) two-way, active-avoidance task. The level of long-term retention of the task was assessed 10 days later. Lesioned rats showed an overall higher performance than control rats both in experiment I (with lesions affecting the rostral Rt and small portions of some adjacent nuclei) and in experiment II (with lesions almost restricted to the rostral Rt). In contrast, detrimental effects on other tasks have been reported in the literature. Although it cannot be ruled out that those differences might be due to methodological factors, they also might be indicative of an action of rostral Rt lesions on certain mechanisms (either indirectly or directly related to information processing) that could be differentially required depending on the kind of learning task. The latter possibility is discussed in terms of the role played by this nucleus as a modulator of thalamocortical transmission, attentional mechanisms and cortical arousal.
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  • 70
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    Experimental brain research 118 (1998), S. 533-540 
    ISSN: 1432-1106
    Keywords: Key words Otolith ; Utricle ; Linear acceleration ; Vestibulo-ocular reflex ; Vestibular compensation ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  We studied horizontal eye movements evoked by lateral whole body translation in nine patients who underwent vestibular nerve section. Preoperatively, all had preserved caloric function on both sides. Testing was performed before, 1 week and 6–10 weeks after surgery. Patients were seated upright in an electrically powered car running on a linear track. The car executed acceleration steps of 0.24 g, randomly to the left and right in the dark. The normal response consisted of a bidirectionally symmetrical nystagmus with compensatory slow phases. Response asymmetry of the slow-phase velocity of the desaccaded and averaged eye position signal was less than 13% in normals (n = 21). Before surgery, patients’ responses were mostly symmetrical. Postoperatively, responses were diminished or absent with head acceleration towards the operated ear in all patients, causing a marked asymmetry which averaged 56% after correction for spontaneous nystagmus. On follow-up, responses regained symmetry. Thus, early after vestibular nerve section, a single utricle produces a normal LVOR only with ipsilateral head translation. Therefore, afferents for the LVOR seem to originate from the mid-lateral area of the macula, where hair cells are stimulated in their on-direction during ipsilateral head translation. Compensation may depend on recovery of the off-directional responses from lateral hair cells of the remaining utricle.
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  • 71
    ISSN: 1432-1106
    Keywords: Key words Neglect ; Space perception ; Visual vertical ; Visual horizontal ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Current models of spatial neglect focus on deficits in the patients’ horizontal or midsagittal plane. However, other evidence suggests that patients with temporoparietal lesions centered on the parieto-insular-vestibular cortex show disturbed spatial perception of the subjective visual vertical and oblique orientation discrimination in another spatial plane, the frontal plane. As the relationship between neglect and spatial orientation deficits is unclear, we examined how patients with and without visual neglect perform visuospatial tasks in the roll plane and how their performance is related to neglect. Thirteen patients with predominantly right parietal lesions and left-sided neglect, 14 control patients without neglect after right-hemispheric cerebral lesions (RBD-controls), 11 patients without neglect after left-hemispheric lesions (LBD-controls), 3 patients with right-sided neglect after left parietal lesions, and 12 normal subjects were investigated. Constant errors and difference thresholds were measured with a PC-based system when the subjects had to adjust a luminous line to their subjective visual vertical, subjective visual horizontal, and in relation to an obliquely oriented reference line. Subjects were oriented with their head and body earth-vertical while sitting in a chair in total darkness. Patients with left-sided as well as those with right-sided neglect showed a significant, in most cases contraversive, tilt of the three spatial orientations (about 5° counterclockwise in the left neglect group and 5.5°–8.5° clockwise in the right neglect group). In contrast, the two patient groups without neglect as well as the normal subjects showed nearly perfect visuospatial judgements with constant errors of less than 0.8°. Difference thresholds were significantly elevated in patients with left neglect and in two of three patients with right-sided neglect, whereas normal control subjects and both control patient groups without neglect performed indistinguishably, having thresholds of one-tenth of those of the neglect patients. Tilt of all three spatial axes was significantly related to the severity of neglect (mean r for unsigned errors, 0.74; for difference thresholds, 0.40), indicating a significant contribution to the symptomatology of left and right spatial neglect. These results indicate a close although not necessarily causal link between spatial orientation deficits in the frontal plane and hemispatial neglect in patients with left or right parietal lesions, surpassing the well-documented impairments of these patients in the horizontal plane.
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  • 72
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    Keywords: Key words Dextromethorphan ; Tirilazad mesylate ; Combination drug therapy ; Cerebral ischemia ; Cerebral blood flow ; Neuroprotection ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Cell death after cerebral ischemia is mediated by a massive release of excitatory amino acids, generation of free radicals, and – a crucial step – calcium influx into cells. We examined the hypothesis that concurrent administration of drugs ameliorating brain damage via different mechanisms would result in a synergistic neuroprotective effect. The neuroprotective efficacy of two clinically available drugs – the N-methyl-d-aspartate and calcium-channel antagonist dextromethorphan (DM) and the antioxidant tirilazad – were studied in monotherapy and in combination in a rat model of transient focal ischemia. Male Sprague-Dawley rats were subjected to 90 min of middle-cerebral-artery occlusion by an intraluminal filament technique. The animals were randomly assigned to one of four treatments (n=10 each): (1) vehicle-treated controls, (2) DM, (3) tirilazad, (4) DM+tirilazad. Drugs or vehicles were administered 15 min before ischemia and at reperfusion. Local cerebral blood flow (LCBF) was bilaterally recorded by continuous laser Doppler flowmetry. Functional deficits were quantified by daily neurological examinations. Infarct volume was assessed planimetrically after 7 days. DM prevented post-ischemic hypoperfusion. Tirilazad did not influence LCBF. Monotherapy with DM or tirilazad improved neurological function and reduced infarct volume by 45% and 48%, respectively. Combination therapy failed to influence neurological recovery and infarct volume. Although, from pharmacological point of view, a synergistic neuroprotective effect is expected, combination of dextromethorphan and tirilazad may lead to mutual inhibition or potentiate adverse effects.
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  • 73
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    Experimental brain research 122 (1998), S. 131-138 
    ISSN: 1432-1106
    Keywords: Key words Synergy ; Isometric ; Finger ; Redundancy ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Based on previous studies, we formulated a principle of error compensation as a major principle of synergy organization during motor tasks performed by a redundant set of effectors. Within the present study, we tested the principle by an investigation of the performance of individual fingers during isometric force production when another task was performed simultaneously. Subjects were asked to press at about 30% of the maximal contraction force with three fingers (index, middle, and ring) acting in parallel. Then, they were required to perform a series of taps at 2 Hz with one of the fingers. In all the tasks, nontapping fingers changed their force production without a time delay with the changes in the force by the tapping finger. During tapping with the index and with the middle finger, both nontapping fingers showed changes in their force negatively correlated with changes in force of the tapping finger. During tapping with the ring finger, two types of behavior could be seen in different subjects with the force of the middle finger going out of phase (group 1) or in phase (group 2) with the force of the ring finger. In both cases, the force of the index finger was out of phase with the force of the ring finger. These changes, on average, induced a compensation for the expected drop in finger force during tapping, ranging in different conditions from 94% to 102%. The ratio of forces produced by the nontapping fingers did not change during the tapping in all the cases except group 2 during ring-finger tapping, when the index finger started to generate significantly higher force as compared to the middle finger. We interpret the data as results of the action of a feed-forward central mechanism leading to parallel changes in forces produced by fingers united into a structural unit.
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  • 74
    ISSN: 1432-1106
    Keywords: Key words Urinary bladder ; Inflammation ; Nucleus centralis of amygdala ; Bed nucleus of the stria terminalis ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  This article is the fifth of a series aimed at mapping brain activities as they result from the development of cyclophosphamide (CP) cystitis in behaving rats using c-fos and Krox-24 expression. The inactive hepatic metabolites of CP are metabolized in the kidney to produce acrolein, which generates cystitis. Data come from animals which were injected once i.p. with either 1 ml saline (sham) or 100 mg/kg CP in 1 ml saline under transient volatile anesthesia and which behaved freely for 1–4 h postinjection, 4 h being the minimum time for cystitis to completely develop. Survival times longer than 4 h were not studied owing to ethical considerations. The first 2 h postinjection cover a period of time over which inputs of multifactorial origin (stress and pain due to the intraperitoneal injection process, possible effects due to the presence of hepatic CP metabolites in blood, cystitis onset) interact in an indistinguishable way; the last 2 h are more cystitis specific as the other effects have vanished. Complete screening of telencephalic levels has been performed. These data complete previously published data at both spinal and subtelencephalic levels. Of all the telencephalic structures, only the bed nucleus of the stria terminalis in the dorsal part of its lateral division (BSTLd) and, to a lesser degree, the nucleus centralis of the amygdala, mostly in its caudal portion (cCeA), appeared to be significantly driven over the most specific cystitis period. Both of these structures had related, but not identical patterns of expression. They both reacted shortly after CP injection, but, while cCeA maintained its activity throughout cystitis development, BSTLd showed a rebound, reaching a peak value when cystitis was fully developed. Both of these areas are the only telencephalic areas to contain high PACAP38 immunoreactivity. This is evidence that, (1) both the BSTLd and cCeA could be the most rostral areas that visceronociceptive inflow would reach when cystitis genesis is under way, and (2) PACAP38 could be one of the neurochemical agents involved in telencephalic visceronociceptive processing. From our complete mapping of brain activities under a fully developed cystitis situation (4 h postinjection), it appears that the activities in BSTLd and cCeA are concomittant with those of both the dorsal vagal complex (DVC), paratrigeminal nucleus (PaT), and the ventrocaudal bulbar reticular formation (vcBRF) at brainstem levels, suggesting they all form the main part of the neural network that subserves the central processing of cystitis-related inputs, comprising pain and associated pseudoaffective responses. Both the DVC and BSTLd, which are the most powerfully driven areas, would be particularly important in such a way. The origin of these activities should be found in both vagal (as sensed through PaT activity) and spinal (pelvic) influences. This network profoundly differs from those reported for painful situations, either somatic or visceral, which controversally accompany positive cardiac inotropism.
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  • 75
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    Experimental brain research 122 (1998), S. 196-202 
    ISSN: 1432-1106
    Keywords: Key words Opioid ; Enkephalin ; Medial vestibular nucleus ; Age ; In vitro ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Extracellular and whole-cell patch clamp intracellular recordings were made from rat medial vestibular nucleus (MVN) neurones in vitro, and their responses to selective μ-, κ- and δ-opioid receptor agonists and antagonists were examined. Of 127 neurones tested, the large majority were inhibited in a dose-dependent manner by the δ-opioid receptor agonists [d-Ala2, d-Leu5]-enkephalin (DADLE) and [d-Pen2, Pen5]-enkephalin (DPLPE). The μ-opioid receptor agonist morphine and the κ-receptor agonist U50,488 did not affect the tonic discharge rate of any of the 63 MVN cells tested. The δ-receptor antagonist naltrindole effectively antagonised the inhibitory effects of DADLE and DPLPE. Weak excitatory responses to high doses of DADLE were seen in only two MVN cells. These results demonstrate the presence of δ- but not μ- or κ-opioid receptors on tonically active MVN neurones. Whole-cell intracellular recordings from MVN cells in a current clamp showed that the DADLE-induced inhibition was accompanied by membrane hyperpolarisation and decrease in input resistance, while voltage clamp experiments showed that DADLE induced an outward membrane current that was reduced but not abolished by 20 mM tetraethylammonium bromide. Thus the mechanisms of action of DADLE in inhibiting MVN cells involve the potentiation of outward K currents, in a similar way to the effects of opioids in other areas of brain. The inhibitory effects of DADLE increased linearly with age, so that the responses to DADLE in the youngest animals used here (60–80 g, approx. 3 weeks of age) were relatively small, increasing significantly over the following 2–3 weeks. This age-dependence may be due to post-natal changes in the density of δ-opiate receptors or the efficacy of the signalling pathways activated by them in the MVN cells over this time.
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  • 76
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    Experimental brain research 122 (1998), S. 185-195 
    ISSN: 1432-1106
    Keywords: Key words Posture ; Equilibrium ; Sway ; Posturography ; Sensory organization test ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Multivariate descriptors of sway were used to test whether altered sensory conditions result not only in changes in amount of sway but also in postural coordination. Eigenvalues and directions of eigenvectors of the covariance of shnk and hip angles were used as a set of multivariate descriptors. These quantities were measured in 14 healthy adult subjects performing the Sensory Organization test, which disrupts visual and somatosensory information used for spatial orientation. Multivariate analysis of variance and discriminant analysis showed that resulting sway changes were at least bivariate in character, with visual and somatosensory conditions producing distinct changes in postural coordination. The most significant changes were found when somatosensory information was disrupted by sway-referencing of the support surface (P=3.2·10−10). The resulting covariance measurements showed that subjects not only swayed more but also used increased hip motion analogous to the hip strategy. Disruption of vision, by either closing the eyes or sway-referencing the visual surround, also resulted in altered sway (P=1.7·10−10), with proportionately more motion of the center of mass than with platform sway-referencing. As shown by discriminant analysis, an optimal univariate measure could explain at most 90% of the behavior due to altered sensory conditions. The remaining 10%, while smaller, are highly significant changes in posture control that depend on sensory conditions. The results imply that normal postural coordination of the trunk and legs requires both somatosensory and visual information and that each sensory modality makes a unique contribution to posture control. Descending postural commands are multivariate in nature, and the motion at each joint is affected uniquely by input from multiple sensors.
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  • 77
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    Experimental brain research 122 (1998), S. 247-252 
    ISSN: 1432-1106
    Keywords: Key words Multisensory integration ; Saccade ; Reaction time ; Gaze shifts ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Information from the auditory and visual systems converges in the nervous system with physiological and behavioral consequences. Most of our knowledge about the rules governing such convergence has been obtained in experiments where the strength or the timing of the individual auditory and visual stimuli has been varied. Relatively little attention has been paid to the spatial relationship between different modalities of stimuli in multisensory experiments. We studied saccadic reaction times of human subjects to bimodal auditory and visual stimulus presentations under two conditions: first, with the targets spatially coincident and, second, with various degrees of spatial separation or disparity. In the first experiment, we found that the saccadic reaction times were consistently shorter than would be predicted by independent processing of information about the visual and auditory targets. These results suggest convergence of multimodal information at one or more loci within the nervous system. In the second experiment, we found that saccadic latency gradually increased as spatial distance between the auditory and visual targets increased. Evidence for neural summation was found over a wide range of spatial disparities. These results suggest that multisensory information can be integrated and have significant influences on behavior over a surprisingly large range of spatial disparity.
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  • 78
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    Experimental brain research 122 (1998), S. 235-246 
    ISSN: 1432-1106
    Keywords: Key words Gaze stabilization ; Head stability ; Posturography ; Vestibulo-ocular reflex ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Dynamic posturography by measurement of center of pressure (COP) is a widely employed technique for evaluating the vestibular system. However, the relationship of COP motion to vestibulo-ocular reflex (VOR) function and image stability on the retina has not been determined previously. To assess these relationships, we report gaze, head, and trunk stability during dynamic posturography in 11 normal volunteers, 7 subjects with unilateral vestibular lesions, and 3 subjects with bilateral vestibular lesions. Posturographic tasks consisted of standing still and standing on a platform that was sliding (0.2 Hz), tilting (0.1 Hz), or covered with a foam cushion 6 cm thick while tilting (0.1 Hz). Each perturbation was imposed in the anterior-posterior and repeated in the medial-lateral direction, in both light and darkness. Subjects viewed (or in darkness remembered) a target located 50, 100, or 500 cm distant. COP, angular eye position, and angular and linear orbit and trunk positions were measured using magnetic search coils and flux gate magnetometer sensors. With the target visible, the velocity of image motion on the retina was on average always less than 1°/s, well within the range consistent with high visual acuity. In darkness, gaze velocity increased for normal and vestibulopathic subjects. During tilt, vestibulopathic subjects had a significantly greater gaze velocity than controls. Gain of the angular VOR (eye velocity/head velocity) was significantly lower in darkness than in light and in vestibulopathic as compared to control subjects. Gain of the VOR was significantly correlated with gaze instability, but variation in VOR gain accounted for only 20–40% of the variance. In darkness, the velocity of the COP was significantly greater in vestibulopathic than control subjects for every condition tested. In light, this difference was small and often not significant. Although spectral analysis of the COP indicated frequencies above 1 Hz that were not observed in motion of the trunk and orbit, root mean square (RMS) velocities of the trunk and orbit in the horizontal plane were higher in darkness and in vestibulopathic subjects, mirroring COP findings. Only in vestibulopathic subjects tested in darkness was there a correlation between COP velocity and gaze velocity; COP velocity was otherwise uncorrelated with gaze. Gaze velocity was greater with near than with distant targets. Vertical VOR gain was higher with near targets. No other significant effects of target distance were found. Head movement strategy, VOR gain, and COP were all unaffected by target proximity. These data show that gaze velocity measurements during dynamic posturography in darkness are sensitive to vestibular loss. With a visible target, both COP and gaze stability of vestibulopathic subjects are difficult to distinguish from normal. During visual feedback, it is likely that image stabilization over the range of frequencies tested is achieved through better head stability and through visual tracking, allowing vestibulopathic subjects to maintain adequate visual acuity.
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  • 79
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    Experimental brain research 122 (1998), S. 260-274 
    ISSN: 1432-1106
    Keywords: Key words Eye-head coordination ; Bilateral vestibular loss ; Adaptation ; Vestibulo-ocular reflex ; Vestibulo-saccadic reflex ; Saccadic gaze shift ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Eye-head coordination during saccadic gaze shifts normally relies on vestibular information. A vestibulo-saccadic reflex (VSR) is thought to reduce the eye-in-head saccade to account for current head movement, and the vestibulo-ocular reflex (VOR) stabilizes postsaccadic gaze while the head movement is still going on. Acute bilateral loss of vestibular function is known to cause overshoot of gaze saccades and postsaccadic instability. We asked how patients suffering from chronic vestibular loss adapt to this situation. Eye and head movements were recorded from six patients and six normal control subjects. Subjects tracked a random sequence of horizontal target steps, with their heads (1) fixed in primary position, (2) free to move, or (3) preadjusted to different head-to-target offsets (to provoke head movements of different amplitudes). Patients made later and smaller head movements than normals and accepted correspondingly larger eye eccentricities. Targeting accuracy, in terms of the mean of the signed gaze error, was better in patients than in normals. However, unlike in normals, the errors of patients exhibited a large scatter and included many overshoots. These overshoots cannot be attributed to the loss of VSR because they also occurred when the head was not moving and were diminished when large head movements were provoked. Patients’ postsaccadic stability was, on average, almost as good as that of normals, but the individual responses again showed a large scatter. Also, there were many cases of inappropriate postsaccadic slow eye movements, e.g., in the absence of concurrent head movements, and correction saccades, e.g., although gaze was already on target. Performance in patients was affected only marginally when large head movements were provoked. Except for the larger lag of the head upon the eye, the temporal coupling of eye and head movements in patients was similar to that in normals. Our findings show that patients with chronic vestibular loss regain the ability to make functionally appropriate gaze saccades. We assume, in line with previous work, three main compensatory mechanisms: a head movement efference copy, an active cervico-ocular reflex (COR), and a preprogrammed backsliding of the eyes. However, the large trial-to-trial variability of targeting accuracy and postsaccadic stability indicates that the saccadic gaze system of patients does not regain the high precision that is observed in normals and which appears to require a vestibular head-in-space signal. Moreover, this variability also permeates their gaze performance in the absence of head movements.
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  • 80
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    Experimental brain research 119 (1998), S. 166-170 
    ISSN: 1432-1106
    Keywords: Key words Locus coeruleus ; Analgesia ; Inflammation ; Naloxone ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  We evaluated the effects of systemic administration of a low dose of naloxone in rats with bilateral lesions in the area of the locus coeruleus (LC) under conditions of unilateral inflammation, compared with those in sham-operated rats. In each group, rats received a single s.c. injection of carrageenan (6 mg in 0.15 ml saline), and effects of a low dose of naloxone (5 μg/kg, i.p.) on thermal nociception were examined at 4 h and 7 days following the induction of unilateral hindpaw inflammation. The antinociceptive effect was assessed by prolongation of the paw withdrawal latency (PWL) to noxious thermal stimuli. Prior to induction of inflammation, the low dose of naloxone had no significant effect on PWLs in either the sham-operated or the LC-lesioned rats. Four hours after carrageenan injection, the low dose of naloxone produced prolongation of PWLs in the sham-operated rats but failed to induce antinociception in the LC-lesioned rats. Antinociceptive effects were observed in both groups of rats 7 days after carrageenan injection. These results suggest that the LC is involved in naloxone-induced antinociception during the early phase of inflammation.
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  • 81
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    Experimental brain research 119 (1998), S. 171-178 
    ISSN: 1432-1106
    Keywords: Key words Rapid body sway ; Leg muscle activity ; EMG pattern ; Ischemic nerve block ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Electromyographic (EMG) patterns of leg muscles associated with rapid body sway were studied in relation to displacement of the center of foot pressure (CFP). Standing subjects were instructed to shift the CFP by swaying their bodies, pivoting at the ankle as rapidly and accurately as possible after an auditory signal. CFP position was designated as N when the subject maintained a relaxed bending posture and as F when a maximally forward-leaning posture was maintained. A serial, stereotyped triphasic EMG pattern was observed in the rapid shift of CFP from N to F: cessation of EMG activity in the gastrocnemius (GC) muscle was followed by a burst in the tibialis anterior (TA) muscle (acceleration phase), and then resumed discharge occurred in the GC muscle with cessation of activity in the TA muscle (deceleration and stop). When the subject shifted the CFP from N to F to different degrees, the duration and amount of EMG activity in the TA muscle during acceleration and the GC muscle in deceleration were proportionate to the amount of CFP displacement associated with forward body sway. To determine the functional roles of sensory inputs from the foot on the triphasic EMG pattern, body sway was studied under the condition of sensory block in the feet induced by ischemia from tourniquets placed bilaterally just above the ankle joints. The triphasic EMG pattern persisted during ischemia. The time of GC cessation and the onset of TA burst at acceleration remained unchanged, but the times of TA cessation and resumption of GC discharge at deceleration were altered during ischemia. Moreover, subjects were unable to stop at F and eventually fell. These results indicate that both amount and duration of EMG activity associated with rapid body sway are functions of the amount of CFP displacement. Somatic sensation from the feet is important for control of burst and cessation timing and duration in leg muscle activity.
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  • 82
    ISSN: 1432-1106
    Keywords: Key words Cortical plasticity ; Phantom limb pain ; Traumatic amputation ; Congenital aplasia ; Neuromagnetic source imaging ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The relationship between phantom limb phenomena and cortical reorganization was examined in five subjects with congenital absence of an upper limb and nine traumatic amputees. Neuromagnetic source imaging revealed minimal reorganization of primary somatosensory cortex in the congenital amputees (M=0.69 cm, SD 0.24) and the traumatic amputees without phantom limb pain (M=0.27 cm, SD 0.25); the amputees with phantom limb pain showed massive cortical reorganization (M=2.22 cm, SD 0.78). Phantom limb pain and nonpainful phantom limb phenomena were absent in the congenital amputees. Whereas phantom limb pain was positively related to cortical reorganization (r=0.87), nonpainful phantom phenomena were not significantly correlated with cortical reorganization (r=0.34). Sensory discrimination was normal and mislocalization (referral of stimulation-induced sensation to a phantom limb) was absent in the congenital amputees. The role of peripheral and central factors in the understanding of phantom limb pain and phantom limb phenomena is discussed in view of these findings.
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  • 83
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    Experimental brain research 119 (1998), S. 224-236 
    ISSN: 1432-1106
    Keywords: Key words Visuomotor transformation ; Sensorimotor integration ; Reference systems ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  In two experiments the involvement of relative and fixed coordinate systems in visuomotor transformations was examined. The experimental task required the successive performance of two movements in each trial, which had to “correspond” to different visual stimuli. One kind of visual display indicated target positions by way of different horizontal positions of a vertical line on a monitor (position mode), while the other indicated movement amplitudes by way of different lengths of a horizontal line (amplitude mode). Formal analysis of variances and covariances of successive individual movements led to the conclusion that in the position mode visuomotor transformations were based on a mixture of relative and fixed coordinate systems, while in the amplitude mode only a relative coordinate system was involved. Thus, visuomotor transformations can be characterized as mixtures of different coordinate systems, and their respective weights in the mixtures are task-dependent.
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  • 84
    ISSN: 1432-1106
    Keywords: Key words Growth-associated protein-43 ; Galanin ; c-jun ; Low-affinity nerve growth factor receptor ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The axotomy reaction in motoneurons after a peripheral nerve transection in the adult animal is characterized by a robust upregulation of alpha-calcitonin gene-related peptide (CGRP) messenger RNA (mRNA) together with mRNAs encoding cytoskeletal and growth-related proteins. Here we have examined whether the nature of the lesion and the age of the animal have any impact on the mRNA regulation in severed cells. Thus, the effect of a sciatic nerve transection in the adult rat was compared with, on the one hand, ventral root avulsions in the adult animal and, on the other hand, sciatic nerve transection in the immature animal. In the two latter cases, a proportion of the lesioned cells die and overall chances of regeneration are small. In the adult animal a sciatic nerve transection induced an upregulation of alpha-CGRP mRNA from the 3rd day after surgery and throughout the first 3 weeks (the time span of the study). Also low-affinity nerve growth factor receptor (p75) and growth-associated protein-43 (GAP-43) mRNAs were upregulated during the entire 3-week period. In contrast, after ventral root avulsion, the expression of alpha-CGRP, c-jun, and p75 mRNAs were normalized within the 1st postoperative week, while GAP-43 mRNA was still upregulated at 3 weeks. Galanin message-associated peptide (GMAP) mRNA became upregulated preferentially in motoneurons subjected to ventral root avulsion, while nitric oxide synthase (NOS) mRNA was expressed exclusively after the latter type of injury. In the immature animal, alpha-CGRP mRNA was downregulated after sciatic nerve transection in rats aged 3 days or 7 days at the time of surgery; while, in contrast, an upregulation was seen in 12- or 21-day-old animals. GAP-43 and c-jun mRNAs were upregulated in lesioned motoneurons of all ages, while GMAP mRNA was upregulated preferentially in lesioned motoneurons of early postnatal animals. p75 mRNA was expressed in unlesioned immature motoneurons until the age of 7–10 days. The downregulation of p75 mRNA in intact cells at this age coincided with a developmental switch in the ability of axotomized cells to express increased levels of p75 mRNA. No expression of NOS mRNA was detectable in lesioned cells of any of the age groups. These results show that the age of the animal and the type of axonal injury are indeed to a high degree influencing the changes seen in the protein expression pattern in axotomized rat motoneurons. The different responses in these paradigms suggest differences in the trophic response from surrounding glia or the trophic responsiveness of lesioned motoneurons. Also, the results may indicate different roles for the studied substances during the regenerative response of lesioned neurons. Of the substances studied here, upregulation of alpha-CGRP and p75 mRNAs best correlated with a possibility of axon regeneration.
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    Experimental brain research 120 (1998), S. 184-192 
    ISSN: 1432-1106
    Keywords: Key words Vestibulo-ocular reflex ; Adaptation ; Neural integrator ; Motor learning ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The phase of the angular vestibulo-ocular reflex (VOR) is subject to adaptive control. We had previously found that adapting the phase of the VOR also produced changes in drift on eccentric gaze-holding, implying a change in the time constant of the velocity-to-position neural integrator. Here we attempted to dissociate changes in gaze-holding drift from changes in the phase of the VOR. In normal human subjects, for 2 h, we alternated 5 min of VOR phase adaptation (sinusoids, 0.2 Hz) with 5 min of making saccades in the light with the head stationary. Afterwards, changes in VOR phase were the same (32% of requested) as those obtained with 1 h of phase adaptation alone, but changes in drift following saccades were much smaller than those found after phase adaptation alone (0.8°/s compared with 5°/s). When measuring drift after VOR steps, however, the changes were closer to those found after phase adaptation alone (3.8°/s). To test the relationship between gaze-holding drift after VOR steps and adaptive changes in VOR phase, we alternated sinusoidal VOR phase adaptation with normal VOR steps in the light. In this paradigm, the adaptive change in VOR phase was about the same as with phase-adaptation alone (35%), but there was now little drift after saccades (1.9°/s) or after VOR steps (0.7°/s). We conclude that the state of the velocity-to-position neural integrator can be altered selectively and rapidly depending upon the task required. Such context-specific adaptation is advantageous, because it allows adjustment of the phase of the VOR without degrading the ability to hold eccentric fixation.
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    Experimental brain research 120 (1998), S. 217-222 
    ISSN: 1432-1106
    Keywords: Key words Orientation acuity ; Oblique effect ; Meridional anisotropy ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Orientation acuity was estimated for vertical and oblique bar stimuli. Discrimination thresholds were affected by changes in the length and width of the targets, falling as bar length was increased and, conversely, rising as the bars were made wider. These changes are complimentary, in that overall discrimination performance can be predicted by a single measure of the orientation “entropy” of the target, namely the height-to-width ratio. The data provide support for a model of orientation coding where discrimination performance is not simply a reflection of the signal-to-noise ratio in single cells in the striate cortex.
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  • 87
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    Experimental brain research 120 (1998), S. 193-201 
    ISSN: 1432-1106
    Keywords: Key words EMG ; Motor unit activity ; Partial denervation ; Interlimb coordination ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  After partial denervation, the remaining motor units (MUs) of adult fast extensor digitorum longus muscle (EDL) expand their peripheral field. The time course of this event was studied using tension measurement and recordings of electromyographic (EMG) activity. The results show that after section of the L4 spinal nerve, when only 5.3 ± 0.63 of the 40 MUs normally supplying EDL muscle remain, the force of individual motor units starts to increase between the 1st and 2nd week after the operation and continues to do so for a further week. The drastic reduction of the number of motoneurones supplying the fast EDL leads to an increase in activity of the remaining MUs. In the 1st week after partial denervation, there was a sharp increase in the EMG activity of remaining motor units. During the next 12 days, this increase became less marked, but EMG activity remained nevertheless significantly higher than that of the unoperated EDL muscle. Many MUs became tonically active during posture. The EMG activity pattern during locomotion was also altered, so that the burst duration was positively correlated with the step cycle duration. Moreover, shortly after partial denervation, the interlimb coordination was disturbed but returned to its original symmetrical use 1–2 weeks later.
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  • 88
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    Experimental brain research 120 (1998), S. 233-242 
    ISSN: 1432-1106
    Keywords: Key words Gravitational force and torque ; Drawing ; Arm kinematics ; Planning ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The purpose of the present experiment was to study the way in which the central nervous system (CNS) represents gravitational force (GF) during vertical drawing movements of the arm. Movements in four different directions: (a) upward vertical (0°), (b) upward oblique (45°), (c) downward vertical (180°) and (d) downward oblique (135°), and at two different speeds, normal and fast, were executed by nine subjects. Data analysis focused upon arm movement kinematics in the frontal plane and gravitational torques (GTs) exerted around the shoulder joint. Regardless of movement direction, subjects showed straight-line paths for both speed conditions. In addition, movement time and peak velocity were not affected by movement direction and consequently changes in GT, for both speeds tested. Movement timing (evaluated through the ratio of acceleration time to total time) changed significantly, however, as a function of movement direction and speed. Upward movements showed shorter acceleration times when compared with downward movements. Concerning the four directions, movements made at 0° and 45° differed significantly from those made at 135° and 180°. Drawing movements executed at rapid speed presented similar acceleration and deceleration times compared with movements executed at normal speed, which showed greater acceleration than deceleration times. In addition, the form of velocity profiles (assessed through the ratio of maximum to mean velocities), was significantly modified only with movement speed. Results from the present study suggest that GF is efficiently incorporated into internal dynamic models that the brain builds up for the execution of arm movements. Furthermore, it seems that GF not only is a mechanical parameter to be overcome by the motor system but also constitutes a reference (vertical direction), both of which are represented by the CNS during inverse kinematic and dynamic processes.
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  • 89
    ISSN: 1432-1106
    Keywords: Key words Basal ganglia ; Hippocampus ; Tectum ; Dopamine ; Serotonin ; Histamine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Previous studies in the rat have shown that the hypothalamic tuberomammillary nucleus, the major source of neuronal histamine, is related to mechanisms of learning, memory, reinforcement, and functional recovery. These functional relationships were found to be partly lateralized. Therefore, we decided to analyze whether unilateral ibotenic acid lesions aimed at this brain region would acutely lead to asymmetries in open-field behavior, and whether they would affect the biogenic amines dopamine and serotonin in the neostriatum, hippocampus, and tectum. We compared this manipulation with unilateral 6-hydroxydopamine lesions of the substantia nigra pars compacta and with unilateral ibotenic acid lesions of the substantia nigra pars reticulata. These lesions were investigated because all three brain areas are anatomically linked to the neostriatum, are related to the neurotransmitters dopamine and serotonin, and play a role in behavioral asymmetry and functional recovery. In support of previous findings, our data show that 6-hydroxydopamine lesions of the substantia nigra pars compacta led to an ipsiversive asymmetry in turning and scanning. Ibotenic acid lesions of the adjacent pars reticulata led to contraversive turning, whereas thigmotactic scanning was reduced bilaterally. In contrast, ibotenic acid lesions of the tuberomammillary nucleus did not affect turning, but led to an ipsilateral asymmetry in scanning. Neurochemically, the 6-hydroxydopamine lesion was mainly characterized by the well-known ipsilateral neostriatal dopamine depletion and increased residual dopamine activity. In hippocampus and tectum, these transmitters were not specifically affected, except for an asymmetry of serotonin in the superior colliculus. The ibotenic acid lesions of the pars reticulata did not deplete neostriatal dopamine, indicating that they spared the dopaminergic output of the substantia nigra. In contrast, they affected dopaminergic and serotonergic measures in the colliculi, which may be due to damage of the nigral GABAergic projection to this brain area. In animals with unilateral ibotenic acid lesions of the tuberomammillary nucleus, several markers of dopaminergic and serotonergic acitivity were increased in the neostriatum, tectum, and hippocampus. This effect may have been due to the loss of inhibition otherwise provided by the wide-ranging histaminergic output of the tuberomammillary nucleus. These results are discussed with respect to the major outputs of the three brain areas, their potential impacts on neurotransmitters in their projection sites, and their role in behavioral asymmetry.
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  • 90
    ISSN: 1432-1106
    Keywords: Key words Event-related potentials ; Readiness potential ; Primary motor cortex ; Supplementary motor area ; Mode of movement selection ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  In two previous studies, the readiness potential (RP) has been reported to be influenced by the mode of movement selection. Freely selected movements were found to have a higher RP amplitude than fixed repetitive movements. This was attributed to the higher demands on planning for the performance of freely selected movements. However, movements in the free mode are distinct from movements in the fixed mode in more than one respect. For example, they are also associated with a higher degree of alteration of the side and/or the finger of movement execution and hence serial “novelty” across blocks of trials. The aim of our study was to establish whether the greater novelty of movements in the free mode could also contribute to the enhanced RP amplitude of movements in the free mode of movement selection by comparing free versus fixed movements performed in long and short sequences that differ in terms of serial novelty. The RP was recorded in 31 healthy young subjects with electrodes placed over Fz, C3, Cz, C4 and Pz. Two types of movement were studied: randomly chosen button presses with right or left index or middle finger (free mode), and repetitive pressing of a predetermined button (fixed mode). We found that: (1) in confirmation of previous studies, the amplitude of the RP was higher for freely selected than free movements; (2) the effect of the mode of movement selection was present over central electrodes but was most pronounced for parietal electrode Pz, with movements in the free mode showing the earliest and greatest increase in negativity at this site; (3) this parietally enhanced negativity in free compared with the fixed mode was absent after the subjects had performed a block of long movement sequences, suggesting that serial novelty of movements also contributed to the effect of mode on the RP amplitude; (4) both the latency and the magnitude of the lateralized readiness potential (LRP) were altered by the mode of movement selection. Movements in the free mode showed an earlier onset of the LRP, which had a higher peak than the LRP prior to movements in the fixed mode. This effect was mainly due to an increased amplitude of the RP over the electrode contralateral to the side of movement prior to freely selected movements. These findings are discussed in relation to previous RP and positron emission tomography studies.
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  • 91
    ISSN: 1432-1106
    Keywords: Key words Neural transplantation ; Tyrosine hydroxylase ; Calcium-binding proteins ; Parkinson’s disease ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Ventral mesencephalon (VM) of fetal rat and human origin grown as free-floating roller-tube (FFRT) cultures can survive subsequent grafting to the adult rat striatum. To further explore the functional efficacy of such grafts, embryonic day 13 ventral mesencephalic tissue was grafted either after 7 days in culture or directly as dissociated cell suspensions, and compared with regard to neuronal survival and ability to normalize rotational behavior in adult rats with unilateral 6-hydroxydopamine (6-OHDA) lesions. Other lesioned rats received injections of cell-free medium and served as controls. The amphetamine-induced rotational behavior of all 6-OHDA-lesioned animals was monitored at various time points from 18 days before transplantation and up to 80 days after transplantation. Tyrosine hydroxylase (TH) immunostaining of the histologically processed brains served to assess the long-term survival of grafted dopaminergic neurons and to correlate that with the behavioral effects. Additional cultures and acutely prepared explants were also fixed and stored for histological investigation in order to estimate the loss of dopaminergic neurons in culture and after transplantation. Similar behavioral improvements in terms of significant reductions in amphetamine-induced rotations were observed in rats grafted with FFRT cultures (127%) and rats grafted with cell suspensions (122%), while control animals showed no normalization of rotational behavior. At 84 days after transplantation, there were similar numbers of TH-immunoreactive (TH-ir) neurons in grafts of cultured tissue (775 ± 98, mean ± SEM) and grafts of fresh, dissociated cell suspension (806 ± 105, mean ± SEM). Cell counts in fresh explants, 7-day-old cultures, and grafted cultures revealed a 68.2% loss of TH-ir cells 7 days after explantation, with an additional 23.1% loss after grafting, leaving 8.7% of the original number of TH-ir cells in the intracerebral grafts. This is to be compared with a survival rate of 9.1% for the TH-ir cells in the cell-suspension grafts. Immunostaining for the calcium-binding proteins calretinin, calbindin, and parvalbumin showed no differences in the neuronal expression of these proteins between the two graft types. In conclusion, we found comparable dopaminergic cell survival and functional effects of tissue-culture grafts and cell-suspension grafts, which currently is the type of graft most commonly used for experimental and clinical grafting. In this sense the result is promising for the development of an effective in vitro storage of fetal nigral tissue, which at the same time would allow neuroprotective and neurotrophic treatment prior to intracerebral transplantation.
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  • 92
    ISSN: 1432-1106
    Keywords: Key words Visual cortex ; Superior colliculus ; Nucleus of the optic tract ; Electrophysiology ; Morphology ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  In most mammals the superior colliculus (SC) and the pretectal nucleus of the optic tract (NOT) receive direct input from the ipsilateral visual cortex via projection neurons from infragranular layer V. We examined whether these projection neurons belong to different populations and, if so, whether it is possible to correlate the electrophysiological features with the suggested function of these neurons. Projection cells were retrogradely labeled in vivo by rhodamine-coupled latex beads or fast blue injections into the SC or the NOT 2–5 days prior to the electrophysiological experiment. Intracellular recordings of prelabeled neurons were made from standard slice preparations and cells were filled with biocytin in order to reveal their morphology. Both cell populations consist of layer V pyramids with long apical dendrites that form terminal tufts in layer I. In electrophysiological terms, 12 of the corticotectal cells could be classified as intrinsically bursting (IB), while two neurons showed a doublet firing characteristic and one neuron was classified as regular-spiking (RS). Intracortical microstimulation of cortical layer II/III revealed that SC-projecting neurons responded optimally to stimulation sites up to a distance of 1000 μm from the recorded cell. The morphological features of the SC-projecting cells reveal an apical dendritic tuft in layer I with a lateral extension of 300 μm, a mean spine density of 65 spines per 40 μm on the apical dendrites located in layer II/III, and a bouton density of 13 boutons per 100 μm on the intracortical axons. Sixteen NOT-projecting neurons exhibited an IB and five cells an RS characteristic. Intracortical microstimulation of cortical layer II/III showed that NOT-projecting neurons responded optimally to stimulation sites up to a distance of 1500 μm. Their morphological features consist of an apical dendritic tuft with a lateral extension of 500 μm, a mean spine density of 25 spines per 40 μm on the apical dendrites located in layer II/III, and a bouton density of 6 boutons per 100 μm on the intracortical axons. When the passive membrane parameters, responses to intracortical microstimulation in layer V, the extension of the basal dendritic field, and spine densities in layers I or V were compared between SC- and NOT-projecting cells, no differences were revealed. Differences were only consistently found in the supragranular layers, either for morphological parameters or for intracortical microstimulation. The results suggest that NOT-projecting and SC-projecting neurons, although biophysically similar, could integrate and transmit different spatial aspects of cortical visual information to their target structures.
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  • 93
    ISSN: 1432-1106
    Keywords: Key words Functional MRI ; BOLD effect ; Motion perception ; Oculomotor pursuit ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  We have studied the effects of pursuit eye movements on the functional magnetic resonance imaging (fMRI) responses in extrastriate visual areas during visual motion perception. Echoplanar imaging of 10–12 image planes through visual cortex was acquired in nine subjects while they viewed sequences of random-dot motion. Images obtained during stimulation periods were compared with baseline images, where subjects viewed a blank field. In a subsidiary experiment, responses to moving dots, viewed under conditions of fixation or pursuit, were compared with those evoked by static dots. Eye movements were recorded with MR-compatible electro-oculographic (EOG) electrodes. Our findings show an enhanced level of activation (as indexed by blood-oxygen level-dependent contrast) during pursuit compared with fixation in two extrastriate areas. The results support earlier findings on a motion-specific area in lateral occipitotemporal cortex (human V5). They also point to a further site of activation in a region approximately 12 mm dorsal of V5. The fMRI response in V5 during pursuit is significantly enhanced. This increased response may represent additional processing demands required for the control of eye movements.
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  • 94
    Electronic Resource
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    Springer
    Experimental brain research 119 (1998), S. 415-426 
    ISSN: 1432-1106
    Keywords: Key words Cortical stimulation ; Ia afferents ; Presynaptic inhibition ; Spinal interneurones ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The effect of transcranial magnetic stimulation was investigated on presynaptic inhibition of Ia terminals in the human upper and lower limb. Presynaptic inhibition of Ia afferents was assessed by three different and independent methods: (1) heteronymous Ia facilitation of the H-reflex (assessing ongoing presynaptic inhibition of Ia afferents in the conditioning volley); (2) long-lasting inhibition of the H-reflex by a group I volley (D1 inhibition, assessing presynaptic inhibition on Ia afferents in the test volley); (3) measurement of the monosynaptic Ia peak evoked in single motor units by a homonymous or heteronymous volley (post stimulus time histogram method). The first two methods were used on the lower limb; the last two on the upper limb. Provided that the corticospinal volley and the explored Ia volley were directed to the same target motoneurones, cortical stimulation evoked significant and congruent changes: (1) In the lower limb, transcranial stimulation provided increased heteronymous Ia facilitation and decreased D1 inhibition, both of which suggest a decrease in presynaptic inhibition of Ia afferents; (2) in the upper limb, transcranial stimulation provided an increase in the radial-induced inhibition of the wrist flexor H-reflex and a decrease in the peak of monosynaptic Ia excitation in single units, both of which suggest an increase in presynaptic inhibition. Selectivity of corticospinal effects was explored by testing presynaptic inhibition of Ia afferents to soleus motoneurones and focusing the transcranial stimulation to excite preferentially different motor nuclei (soleus, quadriceps and tibialis anterior). A cortical-induced decrease in presynaptic inhibition of Ia afferents was seen when, and only when, cortical and peripheral Ia volleys were directed to the same motor nucleus.
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  • 95
    Electronic Resource
    Electronic Resource
    Springer
    Experimental brain research 120 (1998), S. 461-469 
    ISSN: 1432-1106
    Keywords: Key words Hypoglycemic coma ; Specific gravity ; Brain edema ; Tissue osmolality ; Blood-brain barrier permeability ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  To study the effects of pronounced hypoglycemia on brain osmolality and brain edema formation, fasted rats were rendered hypoglycemic by injection of insulin, and subjected to 30 min of hypoglycemic coma. Recovery was accomplished by glucose administration. The change in water content in different brain regions was measured as a change in specific gravity after 30 min of hypoglycemic coma, or 30, 60, and 180 min after glucose administration. Plasma and brain tissue osmolality were measured in separate animals. The results show a significant decrease in specific gravity (increase in water content) in all structures measured (caudoputamen, neocortex, hippocampus, and cerebellum) at the end of the period of coma, as well as after 30 min and 60 min of recovery. At 180 min of recovery, brain water was normalized. The edema affected all structures to the same degree regardless of their vulnerability to hypoglycemic damage. Brain tissue osmolality showed a tendency to decrease with decreasing tissue glucose content. The decrease was significant (P〈0.01) at 30 min of isoelectric coma. In the recovery phase, normal brain osmolality was restored within 30 min. Measurements of blood-brain barrier (BBB) permeability after 30 min of hypoglycemic coma showed no extravasation of Evan’s blue, though a small but significant increase in the permeability for aminoisobutyric acid (AIB) in caudoputamen and in cerebellum was found. To analyze the importance of tissue acidosis for formation of edema, hypoglycemic animals were made acidotic by increasing the CO2 concentration in inspired air to produce an arterial plasma pH of 6.8–6.9. In these animals the edema was of a similar degree to the normocapnic animals, and the permeability for AIB was normal. We conclude that osmolytic mechanisms are not the primary cause of the selective neuronal vulnerability in hypoglycemic coma. Furthermore, the BBB is largely intact during a hypoglycemic insult.
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  • 96
    Electronic Resource
    Electronic Resource
    Springer
    Experimental brain research 120 (1998), S. 479-486 
    ISSN: 1432-1106
    Keywords: Key words Muscle coordination ; Functional role of two-joint muscles ; Cutaneous afferent input from the foot ; Optimization ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  It has been hypothesized previously that because a strong correlation was found between the difference in electromyographic activity (EMG) of rectus femoris (RF) and hamstrings (HA; EMGRF–EMGHA) and the difference in the resultant moments at the knee and hip (Mk–Mh) during exertion of external forces on the ground by the leg, input from skin receptors of the foot may play an important role in the control of the distribution of the resultant moments between the knee and hip by modulating activation of the two-joint RF and HA. In the present study, we examined the coordination of RF and HA during the swing phase of walking and running at different speeds, where activity of foot mechanoreceptors is not modulated by an external force. Four subjects walked at speeds of 1.8 m/s and 2.7 m/s and ran at speeds of 2.7 m/s and 3.6 m/s on a motor-driven treadmill. Surface EMG of RF, semimembranosus (SM), and long head of biceps femoris (BF) and coordinates of the four leg joints were recorded. An inverse dynamics analysis was used to calculate the resultant moments at the ankle, knee, and hip during the swing phase. EMG signals were rectified and low-pass filtered to obtain linear envelopes and then shifted in time to account for electromechanical delay between EMG and joint moments. During walking and running at all studied speeds, mean EMG envelope values of RF were statistically (P〈0.05) higher in the first half of the swing (or at hip flexion/knee extension combinations of joint moments) than in the second half (or at hip extension/knee flexion combinations of joint moments). Mean EMG values of BF and SM were higher (P〈0.05) in the second half of the swing than in the first half. EMG and joint moment peaks were substantially higher (P〈0.05) in the swing phase of walking at 2.7 m/s than during the swing phase of running at the same speed. Correlation coefficients calculated between the differences (EMGRF–EMGHA) and (Mk–Mh), taken every 1% of the swing phase, were higher than 0.90 for all speeds of walking and running. Since the close relationship between EMG and joint moments was obtained in the absence of an external force applied to the foot, it was suggested that the observed coordination of RF and HA can be regulated without a stance-specific modulation of cutaneous afferent input from the foot. The functional role of the observed coordination of RF and HA was suggested to reduce muscle fatigue.
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  • 97
    ISSN: 1432-1106
    Keywords: Key words Gravitational force ; Weightlessness ; Multijoint arm movement ; Movement planning ; Trajectories ; Pointing ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The purpose of the present experiment was to study the way in which the central nervous system (CNS), represents gravitational force during vertical arm pointing movements. Movements in upward (against gravity) and downward (with gravity) directions, with two different mass loads (hand empty and with a hand-held 0.5-kg weight) were executed by eight subjects in a normal gravitational environment. Movements by two cosmonauts, in the two directions, were also tested in a state of weightlessness. Analyses focused upon finger trajectories in the saggital plane. Subjects in a normal gravitational environment showed curved paths for both directions and weight conditions. In addition, downward movements showed significantly smaller curvatures than upward movements. Movement times were approximately the same for all the experimental conditions. Curvature differences between upward and downward movements persisted during space flight and immediately postflight. Movement times from both cosmonauts increased slightly during flight, but returned to normal immediately on reentry in a one-G environment. Results from the present study provide evidence that gravity is centrally represented in an anticipatory fashion as a driving force during vertical arm movement planning.
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  • 98
    ISSN: 1432-1106
    Keywords: Key words Oncogene expression ; Polyamines ; Neuropathology ; Apoptosis ; Olfactory cortex ; Hippocampus ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Microencephalic rats obtained by gestational treatment with the DNA alkylating agent methylazoxymethanol, show a remarkable lack of sensitivity to excitotoxic neuropathology caused by systemic injections of the convulsant neurotoxin kainic acid. Taking advantage of this, we have studied in these rats, as well as in normal rats, the relationship between the induction of cellular signals supposedly related to cell death and the neuronal apoptosis consequent to kainic acid administration. While normal rats responded to the excitatory insult with a large and relatively long lasting increase of the activity of the enzyme ornithine decarboxylase and of the concentration of putrescine in some brain regions, these alterations were much smaller in microencephalic rats. Expression of c-fos in brain regions sensitive to kainic acid was quicker but lasted a noticeably shorter time in microencephalic rats as compared to normal animals. A profusion of apoptotic neurons, labeled by an in situ technique, were observed in the olfactory cortex, amygdala and hippocampus of normal rats injected with kainic acid, in particular 48 h and 72 h after drug administration. At corresponding time intervals and with similar topographic localization, neurons expressing p53 protein were observed. By contrast, microencephalic rats displayed only in a few cases and in a small number apoptotic neurons in restricted areas of the ventral hippocampus and entorhinal cortex. Noticeably, in these cases small populations of p53-expressing neurons were also present in the same areas. The present observations clearly show that oncogenes such as c-fos and p53, as well as ornithine decarboxylase which behaves as an immediate-early gene in the brain under certain circumstances, undergo noticeably lower and/or shorter induction in microencephalic rats exposed to excitotoxic stimuli. In these rats, therefore, the cellular signalling pathways studied here and related to excitotoxic sensitivity and committment to cell death are downregulated as a probable consequence of altered brain wiring.
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  • 99
    ISSN: 1432-1106
    Keywords: Key words EMG ; Finger ; Typing ; Force ; Neural control ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  A single keystroke during touch-typing is a rapid, goal-directed motion of the fingertip which consists of two single-direction movements. The neural control and the role of the finger extrinsic musculature during typing have not yet been explained. The fingertip motion and force, and the intramuscular electromyographic (EMG) activity (fine-wire) of the index finger extrinsic musculature were measured during touch-typing by ten experienced typists. The motions and forces were repeatable qualitatively across keystrokes. A three-burst EMG pattern was observed during a single keystroke. The three bursts were: (1) a burst of extensor activity lifted the finger before the keystroke; (2) a burst of flexor activity followed while the fingertip was moving downward; and (3) a second burst of extensor activity occurred as the fingertip reached the end of key travel. The timing of the third burst suggests the role of the extensors is to remove the fingertip from the keyswitch rather than stop the downward motion of the finger. The collision with the end of key travel stops the downward finger motion. The timing of the finger flexor EMG activity, burst 2, suggests that the flexor contraction principally overcomes the activation force of the keyswitch rather than accelerates the finger downward as expected.
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  • 100
    Electronic Resource
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    Springer
    Experimental brain research 121 (1998), S. 7-19 
    ISSN: 1432-1106
    Keywords: Key words Posture ; Movement ; Anticipatory postural adjustments ; Reaction time ; Electromyogram ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  We studied the changes in the anticipatory postural adjustments (APAs), associated with dropping a load from extended arms and during fast bilateral shoulder flexion movements, when movements were performed in a self-paced manner and under a simple reaction-time instruction. The latter instruction applied time pressure and did not allow the regular pattern of APAs to be used. In particular, the following questions were asked: (1) are there changes in the relative timing of APAs under the reaction time condition; (2) are changes in the relative timing of APAs associated with changes in APAs themselves; (3) can different postural strategies be used to maintain stability under self-paced and reaction time conditions; and (4) are changes in APAs related to actual reaction time or to a change in the instruction? In particular, under reaction-time conditions, APAs occurred later in time, typically simultaneously with the initiation of the focal movement. Additional changes in electromyographic (EMG) patterns in postural muscles included an increase in the amplitude of EMG bursts and “speeding-up” some of the tri-phasic patterns in postural dorsal-ventral muscle pairs. This was accompanied by a smaller early shift of the center of pressure followed by its more rapid delayed displacement. There was considerable variability in the changes of EMG and dynamic characteristics across subjects. Some of the changes in the EMG patterns in postural muscles depended on actual reaction time, while others were related to a change in the instruction and occurred even if actual reaction times were long enough to allow for the typical self-paced APA patterns to occur. These findings can be interpreted as supporting the parallel control hypothesis for the focal movement and postural adjustments. Alternatively, they can be interpreted within a framework that implies the generation of a single control function, which is transformed into two components, one directed at the focal muscles/joints and the other directed at postural muscles/joints.
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