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  • 1990-1994  (2,467)
  • 1970-1974
  • 1955-1959
  • 1890-1899
  • 1992  (2,467)
  • Life and Medical Sciences  (2,215)
  • Rat  (193)
  • Ultrastructure
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  • 1990-1994  (2,467)
  • 1970-1974
  • 1955-1959
  • 1890-1899
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  • 1
    ISSN: 1530-0358
    Keywords: Rat ; Colon ; Anastomosis ; Wound healing ; Tissue adhesive ; Ischemia ; Bursting pressure ; Collagen ; Adhesions
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Fibrin adhesives have been advocated as a protective sealant in high-risk colonic anastomoses to prevent leakage. To assess the effect of fibrin glue sealing on the healing ischemic anastomosis, we compared the healing of sutured colonic anastomoses in the rat, with and without fibrin adhesive (Groups IA and IB), and ischemic anastomoses with and without fibrin adhesive (Groups IIA and IIB). On days two, four, and seven, 10 animals in each group were sacrificed. Adhesion formation was scored, and the in situ bursting pressure was measured. The collagen concentration and degradation were estimated by measuring hydroxyproline. Adhesion formation was more prominent in Groups IB, IIA, and IIB on day four only; abscesses were noted in the ischemic group in four rats. Anastomotic bursting pressure was significantly lower in sealed (IB) and ischemic anastomoses (IIA) than in normal anastomoses (IA) on day four. Sealing of ischemic anastomoses did not change bursting pressures on days two, four, and seven. The relative decrease of collagen in the sealed anastomoses is significantly higher on day four only. It is concluded that sealing of normal colonic anastomoses in the rat has a negative effect on wound healing. Ischemia at the anastomotic site results in weaker anastomotic strength on day four postoperatively. Also in ischemic anastomoses, fibrin sealant does not improve wound healing during the first seven days. Adhesion formation on ischemic intestinal anastomoses was not prevented by fibrin sealing.
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Amino acids 3 (1992), S. 131-138 
    ISSN: 1438-2199
    Keywords: Amino acids ; Osmolytes ; Dehydration ; Rat ; Taurine ; Myoinositol ; Sorbitol ; Betaine ; Glycerophosphorylcholine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary During antidiuresis cells in the renal inner medulla contain large amounts of sorbitol, myo-inositol, glycerophosphorylcholine and betaine to adjust the intracellular osmolality to the extracellular hyperosmolality. Although the accumulation of these four major organic osmolytes in the inner medulla of the dehydrated animal has been a consistent finding, the role of another class of organic osmolytes, amino acids, in osmoregulation in the kidney remains controversial. In the present study, renal responses of four major osmolytes and amino acids to dehydration were investigated using two HPLC systems. Taurine levels were significantly higher in the inner medulla of the dehydrated rats as compared with the control rats, and increased monotonically from the cortex to the inner medulla along the corticopapillary axis in the dehydrated rats. As for four major osmolytes, we confirm previously reported patterns in antidiuresis in greater detail. In conclusion, not only the four major osmolytes but taurine also plays a salient role in the osmoregulation in the kidney.
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  • 3
    ISSN: 1432-1912
    Keywords: Entorhinal cortex ; Isomers ; Low magnesium epilepsy ; Losigamone ; Maximal electroshock test ; Mice ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Losigamone (AO-33) is a recemate of a tetronic acid derivative. The effects of losigamone and its three isomers (AO-242, AO-294 and AO-23) were compared on maximal electroshock (MES) induced convulsions in mice and on different patterns of extracellularly recorded, low Mg 2+ induced epileptiform activity in slices of the rat temporal cortex. Lowering Mg 2+ induced recurrent short discharges in areas CA3 and CA1 while ictaform events that lasted for many seconds were induced in the entorhinal cortex. In the hippocampus the activity stayed stable over a number of hours. In contrast, the ictaform events in the entorhinal cortex changed their characteristics after one to two hours to recurrent discharges of 0.8 to 10 s. Afterdischarges and interictal events were absent. 50 μM AO-242 showed a similar efficacy to 50 μM AO-33 in reducing and blocking epileptiform discharges in areas CA1 and CA3 while 50 μM AO-294 and 50 μM AO-23 had weaker effects than 50 μM AO-33. Concentrations of 50 μM and 100 μM AO-242 showed a similar efficacy to AO-33 on ictaform events in the entorhinal cortex. Late recurrent discharges were also blocked by AO-33 and AO-242 although at higher concentrations (300 μM). The in vitro observations are with respect to order of efficacy in accordance with the in vivo data obtained in the maximal electroshock test in mice. The order of potency in the MES test was AO-242〉AO-33≫AO-294≫ AO-23. The results show that the erythro-isomer AO-23, although active, is much less potent than AO-33. Of the two optical isomers of losigamone the (+) isomer AO-242 is more active than the (−) form AO-294.
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Annals of hematology 65 (1992), S. 50-52 
    ISSN: 1432-0584
    Keywords: TNF ; K 562 ; Leukemia ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We report here that tumor necrosis factor alpha (TNF) induces peculiar cytoplasmic vesicles in the human erythromyeloid leukemia cell line K 562, sensitized to the cytotoxic action of TNF by a treatment with the inhibitor of transcription actinomycin D. These vesicles are well delineated ultrastructurally. The formation of these vesicles is characteristic for the combination of actinomycin D with TNF and precedes the changes of apoptosis and cellular disintegration. These vesicles correspond to an intermediate step in the cytotoxicity caused by TNF and may indicate that reactive metabolites are involved in the mechanism of action of TNF.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Calcified tissue international 50 (1992), S. 524-526 
    ISSN: 1432-0827
    Keywords: Verapamil ; Bone ; Osteopenia ; Rat ; Female ; Intestinal calcium absorption
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary Verapamil inhibits the intestinal absorption of calcium (Ca) and increases serum parathyroid hormone in rats. The effects of verapamil on bone tissue after long-term treatment is, however, not well described. Adult female and male Sprague-Dawley rats received verapamil in their drinking water at a dosage of 0.075 mg/ml (low dose) or 0.75 mg/ml (high dose) for 12 weeks; control rats received only drinking water. All rats were fed a diet containing 0.1% Ca and 0.5% P. In female rats, the amount of bone ash per volume was significantly reduced from 0.742 g/ml in controls to 0.713 g/ml after low-dose treatment of verapamil, and to 0.667 g/ml following high-dose treatment (P〈0.01). The tibial length was increased from 39.7 mm in controls to 40.3 mm or to 40.7 mm after low or high doses (P〈0.01). The tibial volume increased from 0.385 ml in controls to 0.397 ml after low doses and to 0.429 ml after high doses (P〈0.01). In contrast, in male rats the amount of bone ash per volume was significantly increased from 0.578 g/ml in controls to 0.580 g/ml after low doses and to 0.620 g/ml after high doses of verapamil (P〈0.01). The tibial bone volume in males as decreased from 0.633 ml in controls to 0.641 ml after low doses and to 0.583 ml after high doses (P〈0.05). The tibial length in the males was not changed by verapamil. The intestinal absorption of Ca was reduced in male rats from 5.28 in controls to 4.03 (serosa/mucosa) after low-dose treatment and to 2.46 after high-dose treatment with verapamil (P〈0.05). In female rats, the intestinal absorption of Ca did not change after verapamil treatment. Thus, chronic treatment with verapamil in female rats induced osteopenia whereas in male rats bone growth was inhibited.
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  • 6
    ISSN: 1432-0827
    Keywords: Rat ; Osteoblast-like culture ; Ovariectomy ; Estrogens ; Bone blood supply
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary Ovariectomy in the rat induces a rapid osteopenia associated with an elevated bone turnover. One hundred and twenty-day-old rats were ovariectomized (OVX) or sham-operated (n=6–8 per group and per time period studied). 45Ca accretion rate and bone blood flow (microspheres trapping technique) in the femurs were determined at 28, 42, 84, and 119 days after ovariectomy. Both parameters were markedly increased by 84 days and subsided thereafter. At the 42nd day, when bone turnover was maximal, bone marrow and trabecular bone cultures were obtained from shamoperated and ovariectomized animals (n=10/group). Proliferation rate of bone marrow cells and trabecular osteoblast-like cells estimated by fibroblast colony-forming units (FCFU) efficiency and cell counting was markedly increased in primary and secondary cultures in ovariectomy. These data fitted well with the enhanced number of osteoblasts observed in situ in the long bone metaphyses of estrogen-depleted animals. As estrogens were shown in the literature to inhibit proliferation of the red cell line and of other hemopoietic lines, it is possible that estrogens, through a general mechanism, inhibit hemopoietic and stromal lines and also the proliferation of bone marrow-derived trabecular bone cells.
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  • 7
    ISSN: 1432-0827
    Keywords: Periodontal ligament fibroblast ; Mineralized nodule ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary The purposes of this study were to determine whether periodontal ligament (PDL) cells are capable of producing mineralized nodules in vitro and to analyze ultrastructural features of the nodules. Rat PDL cells were obtained from coagulum in the socket at 2 days after tooth extraction and cultured at confluence in standard medium containing Dulbecco's Modified Eagle's Medium supplemented with 10% FBS and antibiotics. To test mineralized nodule formation, cells were further cultured for an additional 3 weeks in the standard medium containing (1) ascorbic acid (50 μg/ml) and sodium β-glycerophosphate (10 mM), (2) ascorbic acid, sodium β-glycerophosphate, and dexamethasone (5 μM), or (3) ascorbic acid alone. Cells were then fixed in 2.5% glutaraldehyde, postfixed in 1% OsO4, and prepared for light and electron microscopy. Threedimensional nodules containing mineralized matrices were formed only when the cells were cultured in the presence of ascorbic acid and dexamethasone. They were composed of multilayered fibroblasts (up to 13 layers), and highly organized collagen fibrils with 64 nm cross-banding patterns between the cell layers. The fibroblasts in the nodules exhibited an elongated shape with a high degree of cytoplasmic polarity throughout the nodule, and have the morphological features of PDL fibroblasts as seen in vivo. Mineral deposition with needle-like crystals was initiated on collagen fibrils located in intercellular spaces of the upper cell layers and became increasingly heavier towards the bottom half of the nodules. X-ray microanalysis and electron diffraction analysis confirmed that mineral deposition contained calcium and phosphate in the form of immature hydroxyapatite. These nodules contained neither osteoblasts nor osteocytes, and have their own morphological organization and characteristics which differ from those formed by bone cells in culture. Therefore, these data suggest that PDL cells are capable of forming mineralized tissue in vitro with the morphological characteristics different from bone mineralized nodules.
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Journal of comparative physiology 170 (1992), S. 645-650 
    ISSN: 1432-1351
    Keywords: Milk ejection reflex ; Positive pressure oscillations ; Motor activity of pups ; Tactile stimulation of nipples ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Changes of positive pressure exerted by pups on nipples during sucking were investigated using anesthetized, lactating dams. It was found that, every 50–60 s, individual pups performed bouts of pressure oscillations (3/s) of high amplitude which lasted about 10–12 s and coincided with periods of increased motor activity. During the intervals, when pups were quiet, series of low-amplitude oscillations (3/s) were also observed. Using a strain measuring method to record the activity of sucking pups, synchronization of activity of two or more pups was found to occur periodically every 25–30 s and, most frequently, 10–30 s before the reflex increase of milk pressure. In further experiments, artificial tactile stimulation was applied to the dam's nipples using the joint action of suction and positive pressure. Following a short-term (10–20 s) increase in frequency and amplitude of artificial nipple stimulation, 60%–80% of all reflexive peaks of milk pressure were elicited with a latency of 19 ± 5 s. This suggests that there are specific conditions under which the stimulation of nipples by pups may trigger the formation of the milk ejection reflex in the rat.
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Journal of comparative physiology 171 (1992), S. 657-664 
    ISSN: 1432-1351
    Keywords: Inferior olivary complex ; Cerebellum ; 3-acetylpyridine ; Harmaline ; Learning ; Memory ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary DA/HAN-strained male rats (pigmented rats) were submitted to two experimental tasks consisting of spatial learning (water-escape) and a passive avoidance conditioning. Both these tasks were performed by different animals. In order to destroy the inferior olivary complex, the animals were injected with 3-acetylpyridine either 9 days prior to the initial learning session or 24 h after completion of the learning task. They were retested (retrieval test) 10 days after the initial learning was achieved. Learning and retention were compared to those noted in control rats. Administration of 3-acetylpyridine before the initial learning did not prevent the spatial learning but the scores were greatly altered and the number of trials needed to reach the fixed learning criterion was much greater than in controls. However, 10 days later the animals had memorized their initial experience. Injection of 3-acetylpyridine after the initial learning session impaired memory: the animals had completely forgotten their initial learning. It can therefore be concluded that lesion of the afferent climbing fibres to the cerebellar cortex alters learning and retention of a spatial task. Such a lesion does not interfere with learning and retention of a passive avoidance conditioning, since in this condition the experimental animals injected with 3-acetylpyridine either before or after the initial learning behave similarly to controls. The effects of the inferior olivary complex lesion are obviously different according to the task to be learnt, suggesting that these two tasks do not require the integrity of the same nervous structures.
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Comparative clinical pathology 2 (1992), S. 166-169 
    ISSN: 1433-2981
    Keywords: Erythrocytes ; Flow cytometry ; Frog hibernation ; Image analysis ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Morphometrical (image analysis of cell and nuclear shape factor), morphological (electron microscopy) and cytochemical (acridine orange fluoro-chromasia and propidium iodide-DNA flow cytometry) features of circulating red blood cells were investigated during two periods of the annual cycle of Rana esculenta: the active phase (July) and the underground hibernating phase (January). The results showed that the hibernating phase is marked by more homogeneity of the red cells, both at nuclear (strongly condensed chromatin) and cytoplasmic level (loss of intact organelles and acridine orange fluorochromasia). The almost complete disappearance of the ‘immature’ erythrocytes from the circulation, during the hibernating phase, should be related to a decrease of haemopoietic activity and to an increase of life span accompanied by uncommon storage in different organs both at vascular and intracellular level.
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  • 11
    ISSN: 1433-2981
    Keywords: FACS ; Rat ; T and B lymphocytes ; FITCand PE-conjugated MoAbs ; Toxicity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract There is a strong need for generation and publication of reference values of immunotoxicity parameters within experimental and toxicological areas. This is particularly true where the type of distribution of reference values and thus the statistical method to be employed is often unknown and will become necessary if current official proposals to implement immune parameters into regulatory toxicity studies are adopted. T and B lymphocytes were identified and quantitated by Fluorescence Activated Cell Sorter Analysis (FACS, using either one or two colours) after labelling of lymphocytes in suspension with fluorescent monoclonal antibodies (MoAbs). For single labelling of T and B lymphocytes, fluorescein isothiocyanate (FITC)-conjugated monoclonal antibody (MoAb) Ox-19 and Mark-1 were used respectively. In double labelling, T and B lymphocytes were identified with phycoerythrin (PE)-conjugated Ox-19 and FITC-conjugated Mark-1 MoAbs respectively. The physicochemical stability shelf-life of labelled T lymphocytes was at least 24 h at 2–8°C permitting overnight storage before FACS analysis, whereas enumeration of B lymphocytes should preferably be done directly after labelling. The sum of the percentages of T and B lymphocytes obtained in the combined T+B lymphocyte analysis with FITC-conjugated Ox-19 and Mark-1 were compared with the sum of values obtained in separate experiments after single labelling, yielding an inaccuracy of 0.3%. The precision of B and T cell analysis after double labelling was found to be 8.2% and 0.5% respectively. Baseline data (reference/normal values) were obtained for rat T lymphocytes (63%–90%) and for B lymphocytes (7.5%–28%).
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  • 12
    Electronic Resource
    Electronic Resource
    Springer
    Virchows Archiv 421 (1992), S. 351-354 
    ISSN: 1432-2307
    Keywords: Krabbe's disease ; Eccrine gland storage ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Lysosomal storage inclusions were observed in skin eccrine gland secretory and myoepithelial cells in three cases of Krabbe's disease. In addition to storage there were numerous degenerative changes, occasionally resulting in cell necrosis. These findings suggest a generalized nature of the storage process in this lysosomal enzymopathy and point to high galactocerebroside turnover in eccrine gland epithelium. This knowledge may be of value in the biopsy diagnosis of Krabbe's disease.
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  • 13
    Electronic Resource
    Electronic Resource
    Springer
    Virchows Archiv 421 (1992), S. 379-385 
    ISSN: 1432-2307
    Keywords: Multicystic mesothelial proliferation ; Immunohistochemistry ; Ultrastructure ; DNA analysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We investigated the clinicopathological findings in five cases of multicystic mesothelial proliferation (MMP). All masses consisted of multiloculated cysts attached to pelvic organs and sometimes growing into the upper abdominal cavity. The cystic spaces were lined by flattened or cuboidal cells. The stroma showed fibrosis, oedema and chronic inflammation. Immunohistochemistry revealed strong positive staining for cytokeratin and epithelial membrane antigen, and focal positivity for vimentin and carcinoembryonic antigen. The endothelial markers were negative. Electron microscopy showed abundant surface microvilli and well-developed basal lamina. DNA analysis identified euploid cell populations in all cases. All but one case had a previous history of abdominal surgery. Despite the worrying appearance the clinical outcome was favourable in all cases; there was one recurrence. Clinical and pathological data support the hypothesis that MMP represent a reactive mesothelial proliferation and not a neoplastic process.
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  • 14
    ISSN: 1432-2307
    Keywords: Eosinophilic granuloma of bone ; Eosinophil granule proteins ; Immunostaining ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Eosinophils from two patients with eosinophilic granuloma of bone (EGB) were studied by combined immunohistochemical and immuno-ultrastructural methods with antibodies directed against three eosinophil granule proteins: major basic protein, eosinophil cationic protein, and eosinophil peroxidase. Immunohistostaining showed the presence and distribution of large numbers of eosinophils in the granuloma. Immuno-ultrastructural methods showed alterations of eosinophil fine structure associated with some steps in the release of granule proteins. No granule extrusion was seen, but rather cationic proteins diffused within cytoplasmic tubulo-vesicular structures. Furthermore, the three granule proteins were found within phagolysosomes of surrounding macrophages, suggesting an interaction between eosinophils and phagocytic cells at the destructive stage of EGB.
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  • 15
    ISSN: 1432-2307
    Keywords: Small cell carcinoma ; Ovary ; Immunohistochemistry ; Ultrastructure ; Literature review
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary This is an immunohistochemical and ultrastructural study of two small cell carcinomas of the ovary with a review of the literature. These cases showed a dimorphic population of small and large cells sharply demarcated from each other. Cytokeratin 18 and vimentin were mainly expressed in the large tumour cells, some of which also stained for alpha-smooth muscle actin. Periodic-acid-Schiff-positive, alpha-1-antitrypsin-positive hyaline globules were present in one case. Ultrastructural findings included filamentous nucleolonema as well as evidence of smooth muscle differentiation. Some of these observations have not been previously reported. Certain of the above features seem to support a germ cell origin of small cell carcinoma, but they cannot be considered specific for germ cell neoplasms. Thus, small cell carcinoma of the ovary cannot be classified into one of the known categories of ovarian tumours at the present time.
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  • 16
    ISSN: 1432-2307
    Keywords: Crystalloid ; Prostatic cancer ; Epithelial membrane antigen ; Phosphotungstic acid hematoxylin stain ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Intraluminal crystalloids (ICr) observed in 19 cases of incidental or invasive human prostatic carcinoma (PCa) and in a case of benign prostatic hyperplasia were examined extensively by immunohistochemistry and electron microscopy. They were brilliantly eosinophilic with haematoxylin and eosin, manifesting needlelike, triangular, rectangular, hexagonal and irregular lump-like in shape. They were strongly positive, dark blue, with phosphotungstic acid -haematoxylin (PTAH) stain in all cases examined. Among the human antibodies tested, epithelial membrane antigen (EMA) gave specifically positive immunostainability with ICr in all cases. Annual ring-like lamellar or concentric structures were detected by electron microscopy. Positive staining of ICr with PTAH and anti-EMA antibody is very useful as a diagnostic marker for PCa in human prostatic tissues.
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  • 17
    ISSN: 1432-2307
    Keywords: Islets of Langerhans ; Monocytic phagocytes ; Streptozocin ; Type 1 diabetes ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The aim of this study was to observe the ultrastructural events, during the onset of diabetes mellitus in the low-dose streptozocin (LDS)-treated mouse model with emphasis on the infiltrating elements. Forty male C57 BL/6J mice were given 40 mg/streptozocin on 5 consecutive days and killed 5, 6, 7, 8, 9, 10, 15, and 18 days after the first injection. Results demonstrated that islet infiltration occurring in LDS-treated mice is characterized by a very early pre-infiltration state in which mononuclear phagocytes in islet capillary vessels were considerably increased in number. A new histopathological time sequence for the early insulitis is described, in which attraction of blood mononuclear phagocytes into the islet capillary lumen is the first step. During the successive stage, occurring on days 6–8 we observed that mononuclear phagocytes migrate through capillary and venule walls into the islet parenchyma, where they differentiate into tissue macrophages. It was only later (step 3) that these macrophages acquired novel properties, typical of their “activated state” and started to phagocytose islet beta-cell debris. These data suggest that during the pre-infiltration and early insulitis the mononuclear phagocyte system plays a key role in the onset of LDS diabetes.
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  • 18
    ISSN: 1432-2307
    Keywords: Malignant rhabdoid tumour ; Uterus ; Immunohistochemistry ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Malignant rhabdoid tumours (MRTs) are highly aggressive neoplasms which most frequently occur in the kidney of young children. Several cases of primary MRT occurring in extra-renal sites have been reported, particularly in the soft tissues. We report a case of primary MRT of the uterus, a very rare site for this neoplasm, with morphological, immunohistochemical and ultrastructural features corresponding to restrictive morphological criteria for MRT. The possible differential diagnoses were considered.
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  • 19
    ISSN: 1432-2307
    Keywords: Diabetes mellitus ; Renovascular hypertension ; Myocardium ; Stereology ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effects of combined renovascular hypertension and diabetes mellitus on the rat heart were investigated in order to detect possible synergistic effects of the two conditions. Hypertensive diabetic and hypertensive non-diabetic animals were compared to diabetic and non-diabetic controls. Hypertension was established for 12 weeks by a surgical stenosis of the left renal artery; diabetes mellitus was maintained for 8 weeks by a single intraperitoneal injection of 60 mg/kg streptozotocin. Light microscopic stereology did not reveal significant divergences between diabetic hypertensives and non-diabetic hypertensives. Hypertension induced a focal perivascular and interstitial fibrosis with increased volume densities of non-vascular interstitium and fibrosis (P〈0.001). Capillary density (QA) was decreased in transverse sections (P〈0.01) and increased in longitudinal sections (P〈0.01). This indicates a three-dimensional remodelling of the capillary bed with an increased number of obliquely running capillaries. At least the length density (LV) of capillaries (mm/mm3) tends to be normalized in long-term renovascular hypertension. At the ultrastructural level, a synergism of hypertension and diabetes mellitus was observed: the volume ratio of mitochondria to myofibrils was significantly decreased in hypertensive diabetics, but not in non-diabetic hypertensives or in diabetics. This may enhance the risk of cardiac deterioration. We conclude that the primary target of the synergistic damage in hypertensive diabetic heart muscle disease is the myocardial cell and not the cardiac interstitium.
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  • 20
    ISSN: 1432-2307
    Keywords: Leiomyoma ; Myometrium ; Cytoskeleton ; Ultrastructure ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The filamentous components of the cytoskeleton in smooth muscle cells of leiomyomata and normal myometrium were studied by immunohistochemistry and electron microscopy. Fourteen patients hysterectomised for non-malignant disease provided leiomyomata of conventional histological type and histologically normal myometrium: four samples of fetal myometrium were studied by immunohistochemistry alone. All samples of leiomyoma and myometrium were strongly positive for α-smooth muscle actin and desmin, the latter often as paranuclear columns or granules. Vimentin was also stained in most samples but less intensely, while cytokeratin stained in about half the samples with an intensity comparable to that of vimentin. By electron microscopy, myofilaments with focal densities were abundant in both normal myometrium and leiomyomata. Intermediate filaments corresponding to the desmin and vimentin demonstrated by immunohistochemistry were also recognised in a variety of architectural arrangements. At one extreme, comparatively small numbers of filaments were loosely distributed around membranous organelles; at the other, filaments formed conspicuous aggregates, largely excluding other organelles and corresponding to the paranuclear granules seen by immunohistochemistry. A comparison of these findings with those of the literature and comments on the possible significance and origin of these aggregates are provided.
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  • 21
    Electronic Resource
    Electronic Resource
    Springer
    Virchows Archiv 420 (1992), S. 219-226 
    ISSN: 1432-2307
    Keywords: Breast ; Granular cell tumour ; Mammography ; Ultrastructure ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Eight cases of benign granular cell tumour of the breast are reported. Seven patients were women and one was male. The age at the time of the excision ranged from 17 to 73 (average 40.1) years. All tumours were positive for S-100 protein and negative for keratin, myoglobin and gross cystic disease fluid protein. In two cases ultrastructural studies revealed findings identical to those in the previously reported cases of granular cell tumours. None of these cases were diagnosed preoperatively. In six cases the clinical and mammographic findings, and in one case the frozen section, led to an erroneous diagnosis of malignancy. The clinico-pathological features of the cases are delineated in order to draw attention to a benign condition which closely simulates malignancy.
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  • 22
    ISSN: 1432-2307
    Keywords: Monoclonal antibody ; Digestive tract ; Colon cancer ; Rat ; Golgi apparatus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A monoclonal antibody, F11C, was raised against rat colon cancer cells. Its immunoreactivity on normal human and rat gut as well as human and rat colonic tumours was studied by the avidin-biotin-peroxidase complex technique. In both normal rat and human gastrointestinal tract, F11C stained surface epithelial cells from the fundus to distal colon, mainly as supranuclear vesicles. These vesicles appeared to be part of the Golgi apparatus on electron microscopy with immunogold labelling. Twenty primary rat colon tumours and 28 of 43 human colon tumours were also stained, with a heterogeneous pattern but much more strongly than the normal colonic mucosa. Biochemical purification suggested that in rat tumours F11C epitope was carried by a high molecular weight glycoprotein. Absorption experiments with synthetic oligosaccharides showed that F11C monoclonal antibody reacted with blood group A-related oligosaccharides. Nevertheless, F11C reactivity on human tissues was not related to the individual ABO or Lewis phenotype.
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  • 23
    ISSN: 1432-2307
    Keywords: Fetus ; Small intestine ; Ultrastructure ; Malnutrition
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Fetal swallowing is established early in development and if fetal ingestion is prevented, the gastrointestinal (GI) tract fails to grow normally. In this article we describe the ultrastructural features of GI tissues developing in the absence of swallowing, in the fetal sheep. We have noted a number of defects in enterocyte morphology. These include abnormal or absence of microvilli, inappropriate cell extrusion, glycogen accumulation and altered lysosomal morphology. Many of these changes resemble those seen in malnourished infants. It is possible that fetal ingestion provides a significant source of nutrients, ensuring adequate GI tract growth in utero, in addition to specific growth factors which may be present in ingested fluid.
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  • 24
    ISSN: 1432-2307
    Keywords: Eccrine porocarcinoma ; Ultrastructure ; Giant cell ; Elastic fibre ; Globular filamentous body
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Five cases of eccrine porocarcinoma were studied by light and electron microscopy. Histopathologically, these could be classified into two types; the common and the giant cell type. The common type was characterized by almost uniform medium-sized cuboidal tumour cells and a formation of well-developed intracytoplasmic lumina. A broad diversity of histopathological and ultrastructural features was seen in these tumours. The tumours of the giant cell type consisted of mononu-clear polygonal cells and bizarre giant cells. This type was considered to be an undifferentiated form of porocarcinoma.
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  • 25
    ISSN: 1434-0879
    Keywords: Neuropeptide Y ; Vasoactive intestinal polypeptide ; Substance P ; Bladder distension ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effect of acute distension on vasoactive polypeptide (VIP)-, neuropeptide Y (NPY)- and substance P (SP)-immunoreactive nerves in the wall of the urinary bladder was investigated. At the age of 3 months, 25 female albino rats underwent forced diuresis combined with balloon obstruction to achieve maximal distension for 3 h. A modified, indirect immunofluorescence detection method was applied 2 days, 7 days and 21 days after distension. A marked, extensive depletion of VIP, NPY-and SP-immunoreactive nerves was observed after distension. This disturbance was reversible, and increased fluorescence of VIP-, NPY- and SP-immunoreactive nerve fibres compared with control specimens was seen in bladder specimens taken even as soon as 21 days after distension. This transient depletion of peptidergic innervation may partly explain the prolonged voiding problems that often occur after acute urinary retention. The depletion of sensory nerves containing SP shortly after distension may explain the transient benefit obtained from distension therapy in patients with painful bladder disease. It is suggested that the increased SP activity during the recovery phase may be related to neurogenic inflammation.
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  • 26
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    Urological research 20 (1992), S. 59-62 
    ISSN: 1434-0879
    Keywords: Urinary bladder ; Overdistension ; Cholinergic Hypoinnervation ; Acetylcholinesterase ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effect of short-term urinary bladder distension on its cholinergic innervation was studied in Sprague-Dawley rats. Distension was induced for 3 h by forced diuresis and balloon outlet obstruction, and whole thick biopsy specimens were taken from the dome and lateral side of the anterior body 2, 7 and 21 days afterwards. The acetylcholinesterase (AChE) method was used to demonstrate the cholinergic nerves in the distended bladder wall. Cholinergic hypoinnervation was observed 7 days after the distension, persisting up to 21 days, although AChE-reactive nerves were then observed to be more numerous. The distribution of hypoinnervation was uneven, being more marked in the lateral side of the anterior body than in the dome. The distribution of AChE-reactive nerves varied even in the same biopsies, with areas of total hypoinnervation occurring next to areas of slightly diminished innervation. This was especially true 21 days after cholinergic innervation, which may in turn explain the prolonged voiding difficulties often seen after catheterization of an overdistended bladder in a patient with urinary retention. The short-lasting effect of bladder dilatation therapy used to treat detrusor instability or interstitial cystitis may be due to the fairly rapid regeneration of cholinergic innervation.
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  • 27
    ISSN: 1434-0879
    Keywords: Interleukin-2 ; Prostatic carcinoma ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The present study was designed to evaluate the effect of a biological response modifier, interleukin-2 (IL-2), on the growth in rats of Dunning (R3327, androgen sensitive) prostatic adenocarcinoma. IL-2 was given to one group of tumour-bearing rats by subcutaneous infusion (Alzet micro-osmotic pump 2002, 14 days) of 424,286 IU/kg per day during 4 weeks. Another group was shamoperated and served as control. Tumour growth was calculated by weekly measurement of tumour volume. IL-2 treatment caused a significant growth delay without any significant toxicity. Plasma testosterone concentrations were similar in both groups and ventral prostatic weights did not differ. Morphometric analyses of epithelial cells, stroma, luminal compartment in tumour tissue and calculation of the number of intratumoral lymphocytes did not show any differences between the two groups. It is suggested that IL-2 treatment can decrease prostatic tumour growth without apparently affecting the testosterone metabolism. Further studies with special interest on the mechanism of action are justified.
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  • 28
    ISSN: 1432-0533
    Keywords: Spinal cord neurofibrillary tangles ; Parkinsonism-dementia complex on Guam ; Guamanian amyotrophic lateral sclerosis ; Ultrastructure ; Immunoelectron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The immunohistochemical and ultrastructural characteristics of spinal cord neurofibrillary tangles (NFTs) were examined in Guamanian amyotrophic lateral sclerosis and in parkinisonism-dementia complex on Guam. The spinal cord NFTs reacted with antibodies to tau protein (tau-2), ubiqitin and paired helical filaments (PHFs). Ultrastructurally, the components of the NFTs were seen as randomly arranged fibrils which were often associated with osmiophilic granules; small bundle-like arrangements were also occasionally observed. Individual NFT fibrils appeared as straight fibrils with a diameter of approximately 15 nm and constricted fibrils with a periodicity of approximately 80 nm. Ultrastructural microscopic examination of specimens stained by the modified Bielschowsky method and with the antibodies revealed silver particles and the products of the tau, ubiquitin and PHF immunoreactions on the NFT fibrils. This is the first demonstration of the fine structure of the spinal cord NFTs.
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  • 29
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    Acta neuropathologica 83 (1992), S. 408-414 
    ISSN: 1432-0533
    Keywords: Eosinophilic granular body ; Astrocytoma ; Ultrastructure ; Immunocytochemistry ; αB-crystallin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Eosinophilic granular bodies (EGBs) are studied immunocytochemically and ultrastructurally in a case of low-grade and a case of high-grade astrocytoma. EGBs are recognized as brightly eosinophilic round bodies of variable size in hematoxylin and eosin-stained sections. Immunocytochemically some EGBs are positive for antibodies raised against αB-crystallin, ubiquitin and glial fibrillary acidic protein with the staining patterns for each being different from one another. Ultrastructurally EGBs consist of membrane-bound round body of various diameter ranging from 50 nm to 20 μm. Small EGBs contain electron-dense homogeneous material with occasional myelin figures, while large EGBs contain small EGB-like structures within electron-dense homogeneous material or loose granular profiles. Our studies demonstrate (1) ultrastructural variety of EGB; (2) and αB-crystallin epitope in EGB; and (3) the presence of EGB in high-grade as well as low-grade astrocytoma.
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  • 30
    ISSN: 1432-0533
    Keywords: Alzheimer disease ; Amyloid angiopathy ; Pericytes ; Microglia ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Ultrastructural studies of serial sections of the vessels with amyloid deposits in the brain cortex of patients with Alzheimer's disease showed that cells in the position of pericytes — perivascular cells - and perivascular microglial cells are producers of amyloid fibrils in the vascular wall. Three types of changes from normal are distinguishable in the vessel wall: (1) semicircular or circular thickening of vascular wall containing a large amount of amorphous material and various number of amyloid fibrils, (2) tuberous amyloid deposits containing both amorphous material and amyloid fibrils, some of the fibrils being arranged in strata and others arranged radially, and (3) amyloid star composed of a predominantly radial arrangement of bundles of amyloid fibrils and a less prominent amorphous component. A mixture of amorphous material and amyloid fibrils is present in cell membrane envaginations of perivascular cells, and occasionally perivascular microglial cells. Bundles of amyloid fibrils are found in altered cisternae of the endoplasmic reticulum and in the channels confluent with the infoldings of the plasma membrane of perivascular microglial cells. The amyloid deposition in the wall of the vessel causes degeneration of endothelial cells and the reduction of, and in some vessels obliteration of, the vessel lumen. In areas affected by amyloid angiopathy, extensive degeneration both of the neuropil and of neurons was observed. These changes were accompanied by astrogliosis. This study demonstrates similarities in amyloid formation in amyloid angiopathy and in β-amyloid plaques in the neuropil and suggests that cells of the mononuclear phagocyte system of the brain (perivascular cells and perivascular microglia) are engaged in amyloid fibril formation.
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  • 31
    ISSN: 1432-0533
    Keywords: Cisplatin ; Spinal ganglia ; Peripheral neuropathy ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We performed a morphological, morphometric and toxicological study on the spinal ganglia and peripheral nerves of the rat after chronic administration of cisplatin (cis-dichlorodiammineplatinum II; DDP) with two different schedules. Severe damage of the spinal ganglia neurons was demonstrated with predominant involvement of the nucleus and nucleolus associated with a decrease in the cell size. Morphological and morphometric changes also occurred in the sciatic and peroneal nerves with the features of axonopathy. All these changes were more marked in the group of rats which underwent the most intense DDP treatment and the tissue platinum concentrations were also higher in this group. This experimental model is the first available for chronic DDP administration in which concomitant spinal ganglia and peripheral nerve damage has been confirmed pathologically. Our study supports the hypothesis that DDP-induced peripheral nerve fiber degeneration may result from nuclear and nucleolar changes in the sensory ganglion cell perikaryon.
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  • 32
    ISSN: 1432-0533
    Keywords: Creutzfeldt-Jakob disease ; Ballooned neurons ; Ultrastructure ; αB-Crystallin ; Stress-response proteins
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary This report concerns ultrastructural and immunohistochemical studies on ballooned neurons of ten patients with Creutzfeldt-Jakob disease (CJD). While abundant ballooned neurons and severe white matter degeneration was seen in six Japanese cases, only occasional ballooned neurons and no white matter degeneration was observed in four cases from the files of Montefiore Medical Center. Ultrastructurally, the ballooned neurons contained granule-coated fibrils of 25 to 40 nm in width and 10-nm neurofilaments. The immunohistochemical studies revealed that most ballooned neurons expressed αB-crystallin, with deposits of reaction products observed in the cytoplasm. A similar intracellular staining pattern was also seen with the antibody to phosphorylated neurofilament proteins (pNFP). Although the proportion of stained ballooned neurons was less, a positive reaction was also observed with antibodies against ubiquitin, stress-response protein 27 (srp 27) and synptophysin, but not with an antibody to srp 72. Our findings suggest that expression of pNFP and synaptophysin by ballooned neurons may reflect axonal impairment and that the presence of αB-crystallin, srp 27 and ubiquitin may be related to the degenerative processes that neurons undergo in CJD.
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  • 33
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    Acta neuropathologica 83 (1992), S. 605-612 
    ISSN: 1432-0533
    Keywords: Colloid cyst ; Endoderm ; Respiratory epithelium ; Third ventricle ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The histogenesis of colloid cyst of the third ventricle remains unsettled. Ultrastructural and immunohistochemical analyses have suggested the following possible origins: (a) neuroepithelium, including paraphysis, ependyma, choroid plexus and tela chorioidea; and (b) endoderm, including respiratory and enteric epithelium. This report describes the ultrastructural features of the lining epithelium in four cases of colloid cyst. Six distinct cell types were recognized: (1) ciliated cells with occasional abnormal cilia; (2) non-ciliated cells with microvilli coated with granulofibrillary material; (3) goblet cells showing discharge of secretory granules; (4) basal cells with prominent tonofilaments and desmosomes; (5) basal-located cells with elongated electron-lucent cytoplasm and scattered membrane-bound dense-core granules (150–350 nm); and (6) small undifferentiated cells with scanty organelles. Junctional complexes were present in the former four cell types but absent in the latter two. The types of epithelial cells and their topographic distribution within the epithelium are both very similar to those of normal respiratory epithelium and to the lining epithelium of intraspinal bronchogenic cyst. The observations made in the present study are compatible with the hypothesis that colloid cysts of the third ventricle originate from the endoderm, most likely the respiratory epithelium.
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  • 34
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    Anatomy and embryology 186 (1992), S. 497-503 
    ISSN: 1432-0568
    Keywords: Skeletal muscle ; Regeneration ; Morphometry ; Histology ; Rat ; Laser
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effect of low-energy laser (He-Ne) irradiation on the rate of skeletal muscle regeneration after partial excision of the rat gastrocnemius muscle was studied using quantitative histological morphometric methods. The injured zones of the experimental rats were subjected to direct He-Ne laser (632.8 nm wavelength) irradiation (6.0 mW for 2.3 min) immediately following injury and once daily thereafter for 5 days. Muscles that were injured as above and subjected to red or room light irradiation served as a control group. The volume fraction (percent of total volume of injured zone) of the mononucleated cells in the injured zone decreased gradually with time after injury, but more rapidly in the laser irradiated muscles than in the control. At 3 days post-injury the myotubes in the laser-irradiated muscles populated a significantly higher percentage (13.9 ± 1.1%) of the injured area than in the control muscles (7.8 ± 1.0%). The volume fraction of the young myofibers in the laser irradiated muscles exceeded 30.6 ± 2.2% and 49.6 ± 5.6% at 8 and 11 days post-injury, respectively, while in control muscles these structures comprised only 9.6 ± 1.0% and 27.2 ± 3.8% of the injured zone at 8 and 11 days after injury, respectively. It is concluded that He-Ne laser irradiation during the regeneration process promotes muscle maturation in the injured zone following partial excision of the rat gastro-cnemius muscle.
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  • 35
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    Anatomy and embryology 185 (1992), S. 271-274 
    ISSN: 1432-0568
    Keywords: Man ; Spermiogenesis ; Postacrosomal ; sheath ; Silver staining ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Applying the silver staining technique, it could be shown that in the early phase of spermiogenesis a layer of argyrophilic material accumulated at the base of the acrosomal vesicle and at the outer side of the nuclear envelope opposite that region, and, later, at the inner side of the plasma membrane near the base of the acrosomal vesicle. During further development of the postacrosomal region of the spermatozoon head, the argyrophilic material associated with the plasmalemma grew caudally to form the postacrosomal dense lamina, while the argyrophilic material associated with the nuclear envelope, staying the same size, shifted to the caudal end of the postacrosomal dense lamina to form the postnuclear band.
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  • 36
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    Anatomy and embryology 185 (1992), S. 559-569 
    ISSN: 1432-0568
    Keywords: Cochlea ; Organ of Corti ; Development ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The development of the rat organ of Corti was studied during the first postnatal weeks. The temporal and the spatial patterns of cochlear development were investigated between 4 and 24 days after birth by means of semi-thin sections at approx. ten equidistant positions along the entire cochlear duct. At all examined positions width, thickness and cross sectional area of basilar membrane, cross-sectional area of tectorial membrane, of cells of Hensen, Claudius and Boettcher and of the organ of Corti were quantitatively analyzed. The most conspicuous maturational changes occur between 8 and 12 days after birth. These are the detachment of the tectorial membrane, the first appearance of filaments within the basilar membrane, the formation of the tunnel of Corti and the opening of the inner spiral sulcus. Quantitative analysis revealed that structures of a given position along the cochlear duct do not develop synchronously. Width of the basilar membrane and cross-sectional area of the tectorial membrane are already mature at the onset of hearing (10–12 days after birth). Length, thickness and cross-sectional area of the basilar membrane as well as cross-sectional area of the organ of Corti and of the cells of Hensen, Claudius and Boettcher still develop after the onset of hearing (up to 20–24 days after birth). We suggest that basic cochlear function is established by structures which are mature before the onset of hearing. Cochlear structures which develop after the onset of hearing might be involved in this improvement during this period.
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  • 37
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    Anatomy and embryology 185 (1992), S. 571-581 
    ISSN: 1432-0568
    Keywords: Cochlea ; Development ; Rat ; Hair cells ; Stereocilia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The development of cochlear receptor cells and their supporting elements was studied by means of semi-thin and ultra-thin sections during the first postnatal weeks in the rat. The temporal and spatial patterns of the receptor cell development were investigated between the 4th and 24th days after birth. At approx. ten equidistant positions along the entire cochlear duct length of inner and outer hair cells, width of outer hair cell triad and stereocilia-length of the outer hair cells were quantitatively analyzed. Striking maturational changes take place before the 12th day after birth, that is, when the onset of hearing occurs. These changes are the formation of the tunnel of Corti, of the Nuel spaces, the appearance of filaments within the supporting elements and the change in cell shape of the hair cells. Between 4 days and 20 days after birth the maturation of outer hair cells is characterized by a decrease of organelles in the cytoplasm and establishment of the subsurface cistern. The quantitative analysis revealed a unique developmental pattern of the length of the outer hair cells, the width of the outer hair cell triad and the stereocilia length of the outer hair cells. Shortly after birth these structures have an almost constant size along the whole cochlear duct, but with increasing age the structures shorten at the cochlear base and enlarge at the apex. This pattern results in the establishment of a basoapical gradient of the above mentioned structures. We assume that this baso-apical gradient is of central importance for the frequency representation.
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  • 38
    ISSN: 1432-0533
    Keywords: Neuronal autophagy ; Bovine spongiform encephalopathy ; Lysosomes ; Ultrastructure ; Vactiolation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The ultrastructural neuropathology of mice experimentally inoculated with brain tissue of nyala (Tragelaphus angasi; subfamily Bovinae), or kudu (Tragelaphus strepsiceros; subfamily Bovinae) affected with spongiform encephalopathy was compared with that of mice inoculated with brain tissue from cows (Bos taurus: subfamily Bovinae) with bovine spongiform encephalopathy (BSE). As fresh brain tissue was not available for nyala or kudu, formalin-fixed tissues were used for transmission from these species. The effect of formalin fixation was compared with that of fresh brain in mice inoculated with fixed and unfixed brain tissue from cows with BSE. The nature and distribution of the pathological changes were similar irrespective of the source of inoculum or whether the inoculum was from fresh or previously fixed tissue. Vacuolation caused by loss of organelles and swelling was present in dendrites and axon terminals. Vacuoles were also seen as double-membrane-bound and single-membrane-bound structures within myelinated fibres, axon terminals and dendrites. Vacuoles are considered to have more than one morphogenesis but the structure of vacuoles in this study was nevertheless similar to previous descriptions of spongiform change in naturally occurring and experimental scrapie, Creutzfeldt-Jakob disease, Gerstmann-Sträussler-Scheinker syndrome and kuru. Other features of the ultrastural pathology of the transmissible spongiform encephalopathies including dystrophic neurites and scrapie-associated particles or tubulovesicular bodies were also found in this study. Neuronal autophagy was a conspicuous finding. It is suggested that excess prion protein (PrP) accumulation, or accumulation of the scrapie-associated protease-resistant isoform of PrP, may lead to localised sequestration and phagocytosis of neuronal cytoplasm and ultimately to neuronal loss.
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  • 39
    ISSN: 1432-0533
    Keywords: Microglia ; Hippocampus ; Ischemia ; Rat ; Major histocompatibility complex antigens
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We show a differential up-regulation of immunomolecules in the rat dorsal hippocampus accompanying neuronal cell death as a consequence of transient forebrain ischemia (four-vessel occlusion model). Using a panel of monoclonal antibodies (mAbs), we have examined the time course of expression of major histocompatibility complex (MHC) antigens class I (OX-18) and class II (OX-6), leukocyte common antigen (OX-1), CD4 (W3/25) and CD8 (OX-8) antigens, CR3 complement receptor (OX-42), as well as brain macrophage antigen (ED2). The study was performed at time intervals ranging from 1 to 28 days after reperfusion. Throughout all post-ischemic time periods, strongly enhanced immunoreactivity on microglial cells in the CA1 region and dentate hilus and, to a lesser extent, in CA3 was demonstrated with mAb OX-42. MHC class I-positive cells (OX-18) appeared on day 2, whereas cells immunoreactive with OX-1 and W3/25 became evident in the CA1 and hilar regions on post-ischemic day 6. In contrast, MHC class II (Ia) antigen was first detected on indigenous microglia by day 13. In some animals, the OX-8 antibody resulted in the labelling of scattered CD8-positive lymphocytes, but perivascular inflammatory infiltrates were absent. No changes in the expression of ED2 immunoreactivity on perivascular cells could be observed. The results show that following ischemic injury, microglial cells demonstrate a timedependent up-regulation and de novo expression of certain immunomolecules, indicative of their immunocompetence. The findings are compared with those obtained in other models of brain injury.
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  • 40
    ISSN: 1432-0568
    Keywords: Training ; Motor nerve terminals ; Neuromuscular junction ; Extensor digitorum longus muscle ; Soleus muscle ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The morphology of nerve terminals in the rat extensor digitorum longus and soleus muscles was studied with light microscopy in 13-week-old male animals after 6 weeks of treadmill running and compared with data from untrained controls. The terminals were stained with methylene blue. Physical training tended to increase the area and length of the nerve terminals in relation to the corresponding muscle fiber diameter, and to reduce the density of nerve terminal varicosities, but significant differences between the trained group and the control group were obtained only in the extensor digitorum longus muscle. The different degrees of effect on the nerve terminals in the two muscles may be due to different abilities to respond to the training, but may also be due to differences in work load caused by the training. The effect of training on extensor digitorum longus junctions may reflect some transformation from fast to slow morphological characteristics.
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  • 41
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    Anatomy and embryology 185 (1992), S. 69-76 
    ISSN: 1432-0568
    Keywords: Human-tumor-associated antigens ; Rat ; Colon
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The patterns of expression of the human-tumor-associated antigens, CO17-1A, GA73-3, BR55-2, GICA19-9, CA50 and carcino-embryonic antigen (CEA) were studied in the normal colonic mucosa (the last three also in the serum) of Sprague-Dawley rats. Four immunohistochemically different segments were identified: caecum, ascending colon, transverse colon and descending colon. The immunohistochemical reactions of the cells at the lower part of the crypt were essential for the distinction of the four segments. In the caecum, the MAbs 17-1A, 73-3 and 19-9 stained the glycocalyx of the cells of the lower part of the crypts and the Golgi apparatus of the intercalated cells (IC). MAb55-2 stained very weakly the goblet-like cells (GLC) of the lower part of the crypt of transverse colon, in addition to a nearly complete lack of reaction in the upper part of the crypts. In the ascending colon, the lower part of the crypts showed a characteristic diffuse staining of the intercalated cells with MAb55-2. The perinuclear and mucosal staining observed in the GLC of the transverse colon with MAbs 17-1A, 73-3 and 19-9 as against the supranuclear and Golgi zone staining observed in the GLC/goblet cells (GC)/columnar cells (CC) of the lower part of crypts of the descending colon with the same MAbs, distinguished the former segment from the latter. The IC demonstrated by immunohistochemistry in the lower parts of the crypts of caecum and ascending colon appear to correspond to the replicating cells of the colonic crypts.
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  • 42
    ISSN: 1432-0568
    Keywords: Vestibular nuclei ; Spinal cord ; Dorsal horn ; Tracing study ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Phaseolus vulgaris leucoagglutinin and wheat germ agglutinin-horseradish peroxidase were iontophoretically injected into different parts of the vestibular nuclear complex (VNC) of the rat. Injections centered into the caudal part of the medial vestibular nucleus revealed a vestibulospinal projection predominantly to the dorsal horn of the cervical spinal cord, besides the expected projection to the intermediate zone (IZ) and ventral horn (VH). While most of the anterogradely labelled fibres could be localized in laminae III to V, some scattered fibres were also seen in laminae I and VI. Lamina II remained free of labelling. The dorsal horn (DH) area with detectable anterograde labelling showed a rostrocaudal extension from C1-C6. Injections into other parts of the VNC labelled fibres and terminals in the IZ and VH while the DH remained almost free of labelling. Additionally, fluorogold and wheat germ agglutininhorseradish peroxidase were pressure- or iontophoretically injected at different levels into the spinal cord to confirm the projection to the dorsal horn by means of retrograde tracing. Labelled neurons in the area of the medial vestibular nucleus (MVN), from which anterograde labelling in the DH was obtained, were only detectable after fluorogold and wheat germ agglutinin-horseradish peroxidase injections into the cervical spinal cord, in particular its DH. This projection from the caudal medial vestibular nucleus to the dorsal horn of the cervical spinal cord probably enables the VNC to influence sensory processing in the DH, in addition to its well-established influence on posture and locomotion via projections to the intermediate zone and ventral horn.
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  • 43
    ISSN: 1432-0568
    Keywords: Badger-placenta ; Ultrastructure ; Ferritin ; Iron transfer regulation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The haemophagous region of the badger (Meles meles L.) placenta is involved in iron transfer, and maternal erythrocytes are the only source of iron for the fetus. This ultrastructural study provides morphological evidence of placental ferritin iron storage intervening if haem-iron uptake exceeds fetal needs. Such placental ferritin is assumed to play an active role in iron transfer regulation. In this paper we demonstrate that this regulatory process of iron transfer by storage in placental ferritin occurs on at least two levels: the cytotrophoblast and the fetal endothelium. The latter could then act as a final monitor in the transfer of iron into the fetal circulation.
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  • 44
    ISSN: 1432-0533
    Keywords: Muscle ; Ultrastructure ; Lysosome ; Metabolic disorder ; Glycogenosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Unusual inclusions with some of the features of “reducing bodies” were encountered in the skeletal muscle biopsy of a 2.5-year-old boy with childhoodonset acid maltase deficiency. The biopsy revealed a vacuolar myopathy with lysosomal storage of glycogen and eosinophilic refractile inclusions in myofibers, which appeared dark blue with the menadione-nitroblue tetrazolium reaction. The significance of the association of inclusions with reducing properties in the setting of acid maltase deficiency is discussed.
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  • 45
    ISSN: 1432-0533
    Keywords: Parkinson's disease ; Ultrastructure ; Catecholomines ; Trans-synaptic degeneration ; Axonal dystrophy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Ultrastructural and biochemical properties of caudate nucleus (CN) biopsies in two patients with advanced Parkinson's disease (PD) were compared with three CN specimens removed during surgery for intracranial tumors. An additional two specimens from neurologically intact patients (59 and 86 years old) were removed during autopsy (performed 3 and 4 h post mortem, respectively) for electron microscopic studies. Dopamine levels in PD were reduced to less than 15% of control values. Both PD patients showed frequent dystrophic neurites and transsynaptic degeneration of neurons and neuritic processes. These changes were not found in CN from the four control individuals. Only a few dystrophic neurites were noticed in one 67-year-old control patient. The development of neuroaxonal dystrophy in CN is consistent with a dying-back process, probably accompanying abnormalities of axonal transport in PD. Transsynaptic degeneration of neurons in CN very likely represents a morphological marker of disease severity. The occurrence of this change may account for the poor clinical response of patients with advanced PD to intracerebral implantation of dopaminergic tissues.
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  • 46
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    Acta neuropathologica 83 (1992), S. 379-385 
    ISSN: 1432-0533
    Keywords: Hypoglycemia ; Hypothermia ; Neuronal damage ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effects of hypothermia on hypoglycemic brain damage were studied in rats after a 30-min period of hypoglycemic coma, defined as cessation of spontaneous EEG activity. The rats were either normothermic (37°C) or moderately hypothermic (33°C). Morphological brain damage was evaluated after various periods of recovery. Hypothermic animals with halothane anesthesia never resumed spontaneous respiration, thus requiring artificial ventilation during recovery (maximally 8h). In contrast, when isoflurane was used as the anesthetic agent, all animals survived and were examined after 1 week of recovery. There was a tendency towards gradually higher arterial plasma glucose levels during hypoglycemia with lower body temperature. The time period from insulin injection until isoelectric EEG appeared was gradually prolonged by hypothermia, and was shorter when isoflurane was used for anesthesia. Brain damage was examined within the neocortex, caudoputamen and hippocampus (CA1, subiculum and the tip of the dentate gyrus). Damage to neurons was found to be of two types, namely condensed dark purple neurons (pre-acidophilic) and shrunken bright red-staining neurons (acidophilic). In the neocortex, no clear influence of temperature on the degree of injury was seen. In the caudoputamen, the number of injured neurons clearly decreased at lower temperature (33°C,P〈0.001) when halothane was used, while no such difference was seen when isoflurane was used as the anesthetic agent. Likewise, a protective effect of hypothermia was seen in subiculum (P〈0.01) when halothane, but not isoflurane was used. Damage to CA1 neurons was mild in both groups with halothane, but slightly less frequent (P〈 0.05) in the hypothermic group, in which the majority of animals showed no damage. No protection of hypothermia was seen in the animals with isoflurane anesthesia. Furthermore, with isoflurane, more damaged CA1 cells were seen in the normothermic situation as compared to when halothane was used (P〈0.01). In contrast, damage to the tip of the dentate gyrus was remarkedely resistant to hypothermia, with the majority of animals showing the same degree of damage as the normothermic ones irrespective of the anesthetic agent used. In summary, hypothermia seemed to have only a partial protective effect on the development of hypoglycemic brain damage, the effects differing between regions previously described to be selectively vulnerable to hypoglycemia, and also differing when halothane or isoflurane were used as anesthetic agents. While long-term survival was achieved with the use of isoflurane, the protective effect of hypothermia seemed to be lost.
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  • 47
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    Acta neuropathologica 83 (1992), S. 659-663 
    ISSN: 1432-0533
    Keywords: Eosinophilic inclusion ; Neuroglia ; Astrocyte ; Aicardi's syndrome ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Intracytoplasmic and brightly eosinophilic inclusions within neuroglias are reported in a patient with Aicardi's syndrome. Most inclusion-bearing neuroglias were protoplasmic astrocytes in the cerebral cortex. Compared with similar eosinophilic and intracytoplasmic inclusions in other studies using both light and electron microscopy, the inclusions in this report are regarded as being novel and not previously described. Ultrastructually, the inclusions were composed of electron-dense granules and amorphous substances, and were not surrounded by a limiting membrane. They were numerous in the cerebral cortex, especially in part of the microgyrus, but absent in the deep cerebral white matter, subcortical nuclei, brain stem and the cerebellum. Therefore, they may be closely associated with brain malformation and congenital astrocytic dysfunction. They also suggested a functional difference in protoplasmic astrocytes themselves, according to the differentiation of related gray matter.
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  • 48
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    Anatomy and embryology 186 (1992), S. 145-152 
    ISSN: 1432-0568
    Keywords: Harderian gland ; Tubuloalveolar endpieces ; Serous endpieces ; Ultrastructure ; Opossum
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The Harderian gland of the North American opossum (Didelphis virginiana) is large and well developed, despite the absence of a nictitating membrane in the adult of this species. The elongate glands are surrounded by a delicate connective tissue capsule from which thin septae extend, subdividing the gland into numerous lobules. The secretory units of the opossum Harderian gland are drained by a well defined but not extensive intralobular and interlobular duct system. Most of the secretory end pieces consist of tubuloalveolar units with widely dilated lumina filled with secretory product. Numerous intact lipid vesicles suspended within an amorphous material constitute the luminal contents. Cells lining the tubuloalveolar secretory endpieces are usually columnar in shape, and characterized by numerous lipid-containing secretory vesicles and aggregations of polytubular complexes 40–60 nm in diameter. In addition, these cells contain numerous large irregularly shaped mitochondria, whose matrix is of considerable electron density. Intralobular and interlobular ducts are lined by electron-lucent epithelial cells that lack both the lipid-containing vesicles and the large mitochondria, although typical smaller mitochondria are found scattered within the cytoplasm. Both secretory endpieces and ductal elements are invested by an abundance of myoepithelial cells. A second, smaller serous type of secretory unit may occur near the centre of some Harderian gland lobules. In these units secretory tubules and acini are compactly arranged surrounding a narrow lumen. Serous cells are pyramidal in shape and the cytoplasm is characterized by numerous electron-dense secretory granules and scattered profiles of rough endoplasmic reticulum. Basolateral cell membranes show extensive infoldings and intercellular canaliculi are present. The overall size of cells forming the serous secretory units is much less than that comprising the tubuloalveolar secretory endpieces.
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  • 49
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    Acta neuropathologica 83 (1992), S. 518-524 
    ISSN: 1432-0533
    Keywords: Amyotrophic lateral sclerosis ; Upper motor neurons ; Ultrastructure ; Neurofilament ; Ubiquitin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The pathological alterations in upper motor neurons were investigated in 27 cases of adult-onset sporadic amyotrophic lateral sclerosis (ALS). No signficant cytoskeletal alterations were found in the Betz cells of any of the cases except one, although cytoskeletal pathology was consistently present in lower motor neurons. The one case had severe circumscribed atrophy of the precentral gyrus and, microscopically, had argentophilic intracytoplasmic inclusions in Betz cells and other pyramidal neurons in the primary motor area as eell as in the lower motor neurons. Immunocytochemically these inclusions contained the epitope of phosphorylated neurofilament and ubiquitin and ultrastructurally consisted of granule-associated filaments with neurofilaments. This is the first demonstration of alterations of cytoskeleton and ubiquitination in the giant cells of Betz, an established subset of upper motor neurons in ALS. Thus, although uncommon, cytoskeletal changes can be found in upper motor neurons in some ALS cases.
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  • 50
    ISSN: 1432-0533
    Keywords: Primary leptomeningeal glioma ; Ultrastructure ; Basal lamina ; Laminin ; Heterotopic glial tissue
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We studied a case of primary leptomeningeal glioma (PLG) on the left parietal lobe of a 74-year-old woman and compared the tissue with heterotopic glial tissue from another case. The PLG tumor consisted of spindle-shaped cells with marked nuclear atypism, which tended to be arranged in a fascicular pattern, and the majority of its cells were positive for glial fibrillary acidic protein. Ultrastructural examination demonstrated that most of the tumor cells contained intermediate filaments and often junctional complexes were present on their plasma membranes. Frequently, basal lamina-like structures surrounding the tumor, cell surfaces were observed. Laminin immunohistochemistry clearly demonstrated a fine network of linear positive staining around the cytoplasm and processes of the tumor cells. The ultrastructure of the heterotopic glial tissue consisted of many astrocytes partially surrounded by basal lamina. These findings strongly suggest that PLG is a distinct tumor, which arises from the heterotopic astrocytes within the subarachnoid space.
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  • 51
    ISSN: 1432-0533
    Keywords: Peripheral nerve biopsy ; HIV infection ; Ultrastructure ; in situ hybridization
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A peripheral nerve biopsy was performed in 15 patients with human immunodeficiency virus (HIV) infection and polyneuropathy. Two cases [1 asymptomatic, 1 AIDS-related complex (ARC)] presented with chronic inflammatory demyelinating polyneuropathy; there was 1 case (asymptomatic) of mononeuropathy multiplex and 12 cases (1 asymptomatic, 1 ARC, 10 AIDS) with distal symmetrical polyneuropathy. Epi- or endoneurial microvasculitis was observed in 6 cases. Electron microscopy showed that nerve fiber lesions were mainly axonal. Severe segmental demyelination was also present in both cases of chronic inflammatory demyelinating polyneuropathy, with characteristic features of active demyelination in one. Numerous plasmacytoid cells were found in the endoneurium in 4 patients. Tubuloreticular inclusions were present in endothelial cells in the 10 cases with AIDS but absent in the other patients. Direct immunopathological examination with anti-immunoglobulin sera was negative in all cases. HIV was evidenced by in situ hybridization in 2 AIDS patients; no Epstein-Barr virus or cytomegalovirus was detected.
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  • 52
    ISSN: 1432-0533
    Keywords: Alzheimer's disease ; Tissue culture ; Microglia ; Amyloid ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The function of microglia associated with β-amyloid deposits still remains a controversial issue. On the basis of recent ultrastructural data, microglia were postulated to be cells that form amyloid fibrils, not phagocytes that remove amyloid deposits. In this electron microscopic study, we examined the ability of microglia to ingest and digest exogenous amyloid fibrils in vitro. We demonstrate that amyloid fibrils are ingested by cultured microglial cells and collected and stored in phagosomes. The ingested, nondegraded amyloid remains within phagosomes for up to 20 days, suggesting a very limited effectiveness of microglia in degrading β-amyloid fibrils. On the other hand, we showed that in microglial cells of classical plaques in brain cortex of patients with Alzheimer's disease, amyloid fibrils appear first in altered endoplasmic reticulum and deep infoldings of cell membranes. These differences in intracellular distribution of amyloid fibrils in microglial cells support our observations that microglial cells associated with amyloid plaques are engaged in production of amyloid, but not in phagocytosis.
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  • 53
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    Acta neuropathologica 84 (1992), S. 238-243 
    ISSN: 1432-0533
    Keywords: Creutzfeldt ; Jakob disease ; Tubulovesicular structures ; Prion diseases ; Ultrastructure ; Transmissible spongiform encephalopathies
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary By electron microscopy tubulovesicular structures (TVS) have been consistently observed in brain tissue of transmissible spongiform encephalopathies such as natural and experimental scrapie, bovine spongiform encephalopathy and experimentally induced, but not naturally occurring, Creutzfeldt-Jakob disease (CJD). For the first time we report here the presence of TVS in human brains with CJD as detected by transmission electron microscopy. TVS were observed in all three CJD specimens (two biopsies, one autopsy), but they were rare and were found only in one or two location(s) per grid. TVS were seen in distended pre- and postsynaptic terminals and measured approximately 35 nm in diameter; they were smaller and of higher electron density than synaptic vesicles. Their occurrence in all types of transmissible spongiform encephalopathies irrespective of the affected host and the strain of the infectious agent suggests their biological significance.
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  • 54
    ISSN: 1432-0533
    Keywords: Traumatic brain injury ; Hypothermia ; Blood-brain barrier ; Hypertension ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effects of moderate hypothermia on blood-brain barrier (BBB) permeability and the acute hypertensive response after moderate traumatic brain injury (TBI) in rats were examined. TBI produced increased vascular permeability to endogenous serum albumin (IgG) in normothermic rats (37.5°C) throughout the dorsal cortical gray and white matter as well as in the underlying hippocampi as visualized by immunocytochemical techniques. Vascular permeability was greatly reduced in hypothermic rats cooled to 30°C (brain temperature) prior to injury. In hypothermic rats, albumin immunoreactivity was confined to the gray-white interface between cortex and hippocampi with no involvement of the overlying cortices and greatly reduced involvement of the underlying hippocampi. The acute hypertensive response in normothermic rats peaked at 10 s after TBI (187.3 mm Hg) and returned to baseline within 50 s. In contrast, the peak acute hypertensive response was significantly (P〈0.05) reduced in hypothermic rats (154.8 mm Hg, 10 s after TBI) and returned to baseline at 30 s after injury. These results demonstrate that moderate hypothermia greatly reduces endogenous vascular protein-tracer passage into and perhaps through the brain. This reduction may, in part, be related to hypothermia-induced modulation of the systemic blood pressure response to TBI.
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  • 55
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    Acta neuropathologica 85 (1992), S. 55-70 
    ISSN: 1432-0533
    Keywords: Excitotoxin ; Substantia nigra ; Neuronal degeneration ; Calcification ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The excitotoxin ibotenic acid (IBO) induces local calcium deposits upon injection into rat substantia nigra. Their formation has been investigated at the ultrastructural level in a time course study from 2 days to 8 weeks survival. Potassium bichromate stain was used to visualize pathological calcium accumulation. Two days after IBO application, reaction product for calcium was observed in mitochondria of degenerating perikarya and dendrites, but not in axons, boutons or glia. Four days after the lesion, calcium stain was found, in addition, in a seemingly free form in a few dendrites, especially those still contacted by intact boutons and not sequestrated by invading glia. Two days later, most of these calcium-accumulating dendrites were separated by astroglia from their synaptic partners. At the border between glia and dendrite a fibrillar matrix was formed which further accumulated calcium. During the following weeks this matrix enlarged stepwise and was infiltrated with calcium, thus giving a picture resembling the annual growth rings of trees. The evolving bodies incorporated smaller deposits in their vicinity, finally representing the large concretions seen at the light microscopic level from the 4th postoperative week onward. Similarities and dissimilarities of these observations with the results from other ultrastructural studies on excitotoxin lesions are detailed. It is suggested that the different outfit of neuronal subpopulations and of glia with ligand-gated and metabotropic glutamate receptors in the single brain region, as well as the local response repertoire of glial cells towards the excitotoxic injury with the subsequent formation of a calcium-accumulating matrix provide the molecular basis for the formation of calcium deposits.
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  • 56
    ISSN: 1432-0568
    Keywords: Prolactin cell ; Met-enkephalin ; Immunocytochemistry ; Ultrastructure ; Morphometr ; Rat(Sprague-Dawley)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A stimulatory effect on prolactin secretion had been describe after acute and systemic administration of met-enkephalin, but the effects of this opioid after chronic administration has not been reported, and the response of mammotroph cells is not clear. As a complement to previous studies, a morphometric analysis (light and electron microscopy) was carried out on prolactin cells from female rats treated chronically with met-enkephalin. Clear features of cellular hyperactivity appeared after chronic and systemic administration of the opioid, and these persisted for two weeks. The changes consisted in increases of cellular, cytoplasmic and nuclear areas, volume and surface densities of the Golgi complex and rough endoplasmic reticulum, as well as the numbers of exocytotic figures. These morphological alterations were paralleled by an increase in serum prolactin levels as detected by RIA. It is concluded that the increase in the synthesis and secretory activity of prolactin cells following chronic and systemic administration of met-enkephalin is very similar to those observed after acute and intraventricular administration.
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  • 57
    ISSN: 1432-0568
    Keywords: Superior colliculus ; Periaqueductal gray ; NADPH-diaphorase ; Golgi method ; Neuronal types ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We have studied the laminar distribution of reduced nicotinamide dinucleotide phosphate diaphorase (NADPH-d) activity and the morphology of positive neurons in the superior colliculus (SC) and the underlying periaqueductal gray (PAG) of the rat. The morphology of NADPH-d-positive neurons has been compared to that of Golgi-impregnated cells. The highest activity occurs in the stratum zonale and stratum griseum superficiale, contrasting with the pale neuropil in the stratum opticum, where only a few positive neurons are found. In the stratum griseum intermedium positive neurons are grouped in patches separated by narrow, NADPH-d-negative bands. In the deeper layers, the neuropil is NADPH-d-negative, and few neurons show enzymatic activity. In contrast, numerous neurons in the dorsolateral part of the PAG are intensely positive. They are continuous with the positive neurons in the stratum album profundum, with no clear border between the two centers. In both SC and PAG, only small and medium sized neurons are NADPH-d-positive. In comparison with Golgi material, all types of small neurons in the superficial layers show NADPH-d activity; NADPH-d histochemistry, however, does not visualize the characteristic dendritic appendages of these neurons. The large neurons of the SC and PAG, probably representing the long-projecting neurons of these centers, do not contain the enzyme.
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  • 58
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    Anatomy and embryology 185 (1992), S. 201-206 
    ISSN: 1432-0568
    Keywords: Development ; Mouse ; Peripheral nerves ; Schwann cells ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The distal course of the sensory nerve fibres on the palmar side of the hand of 12-day-old mouse embryos was followed by serial ultrathin cross-sections of conventionally fixed tissue. Small nerves fibres are to be found in the space between the layer of the cutaneous blood vessels and the epidermis. A special arrangement of the tissue which is traversed by the nerve fibres is not visible. In most cases the nerve fibres are in intimate contact with fibroblasts. More distally the nerve fibres consist only of one axon encircled by a Schwann cell. The sheath of the Schwann cell decreases gradually, and finally disappears completely. The distal tips of the naked axons are a few μm ahead. In some cases they are considerably enlarged and contain only a fine fuzzy material without special cell organelles. Other axons may end in a more finger-like fashion, and contain also in the naked parts many cell organelles. Also the naked axons contact fibroblasts over long ranges. Collagen was not found aligned to the distal nerve fibres.
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  • 59
    ISSN: 1432-0568
    Keywords: Mandibular condyle ; Calcified cartilage ; Ultrastructure ; Maturation ; Macaca fascicularis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In an attempt to show maturational alterations in the calcified cartilage, mandibular condyles of four growing and four adult male monkeys (Macaca fascicularis) were studied using light microscopy as well as transmission and scanning electron microscopy. All specimens were initially fixed by perfusion in the presence of ruthenium red. For examination of the hard tissue surfaces in the scanning electron microscope, uncalcified tissues were removed with sodium hypochlorite. In growing animals, almost the entire hard tissue surface in the joint region of the condyle was formed by calcified cartilage, while in adult animals, calcified cartilage was confined to load-bearing regions. In growing animals, the appearance of the calcified cartilage surface suggested a continuously advancing mineralizing front similar to that seen in the epiphyseal plate. Chondrocytes mostly exhibited a terminal stage of hypertrophy, and seemed to die and get lost through vascular invasion and subsequent endochondral ossification. In adult animals, most of the calcified cartilage surface appeared comparatively stable, and resembled the tidemark of articular cartilage. Chondrocytes were usually small and appeared viable. However, on the adult condyles, there were always circumscribed islands where chondrocytes and the pattern of mineralization resembled those seen in growing animals. In these regions, prominent chondroclastic activity indicated extensive articular remodelling. These observations suggest that at the end of somatic growth, condylar calcified cartilage undergoes considerable maturation from a type reminiscent of hyaline growth cartilage to a type resembling articular cartilage. Concomitantly, chondrocytes appear to change their developmental program, in that they stop enlarging and lose their commitment to death. However, they may be able to retain, or switch back to, a more immature stage, in case there is need for extensive articular remodelling.
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  • 60
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    Anatomy and embryology 185 (1992), S. 217-223 
    ISSN: 1432-0568
    Keywords: Rat ; Embryo culture ; Cephalic neurulation ; 5-Azacytidine ; Methylation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Head-fold stage rat embryos (9.5 days of gestation) were cultured for 48 h in rat serum with or without 0.8 μM 5-azacytidine. Incomplete closure of the cephalic neural tube was observed in 5-azacytidine-treated embryos cultured for 48 h (25-somite stage). Control embryos showed complete fusion of cephalic neural folds at 33 h (16-somite stage) in culture. Drug administration or removal experiments revealed that embryos were sensitive to 5-azacytidine during 6–12 h of culture (three to five somite stages). Electron microscopical studies indicated that the arrangement and fine structure of cephalic neuroepithelial cells were almost the same in control and treated embryos. There was no significant difference in DNA and protein contents between control and treated embryos cultured for 36 h. Immunocytochemical observations using 5-methylcytosine-specific antibody revealed that the staining of neuroepithelial cells in the median part of the transversely sectioned cephalic neural plate, and of mesenchymal cells near the apices of the plate, was suppressed by 5-azacytidine. These results suggest that DNA methylation of these cells plays an important role in closure of the cephalic neural tube.
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  • 61
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    Archives of dermatological research 284 (1992), S. 259-265 
    ISSN: 1432-069X
    Keywords: Genodermatoses ; Ultrastructure ; Membrane structures ; Abnormal keratinosomes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The recessively inherited congenital ichthyoses have ultrastructural features which indicate abnormal epidermal lipid metabolism. The ultrastructural markers of the three recessive congenital ichthyosis groups are lipid droplets in horny layers (type I), cholesterol clefts (type II) and membrane structures (type III). We describe six patients from five families belonging to the last group. The variable clinical phenotype alone does not allow the delineation of this disease, but together with the ultrastructural characteristics the subtype is unequivocal. In addition to the membrane structures, half of the cases showed abnormal keratinosomes and vesicular complexes. Membrane-bound vacuoles and needle-like slits were exceptionally found. The onset of the ichthyosis was variable, in contrast to other patients described under the heading recessive congenital ichthyosis.
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  • 62
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    Archives of dermatological research 284 (1992), S. 95-99 
    ISSN: 1432-069X
    Keywords: Chromoblastomycosis ; Host-fungus relationship ; Morphometry ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To investigate the histological distribution and the morphology of the fungi and the tissue reactions in chromoblastomycosis, especially in the process of trans-epidermal elimination, cutaneous lesions of two patients with this disease were studied morphometrically and ultrastructurally. In the dermis, most of the fungal elements appeared as sclerotic cells and their cell wall showed an irregular, worm-eaten leaf-like appearance; they seemed to be continuously attacked by polymorphonuclear neutrophils. The epidermis eliminated 10–20% of all the organisms in the skin lesions, and the hypha-forming activity tended to be higher in the epidermis than in the dermis. Ultrastructurally, basal keratinocytes facing the dermal abscess containing fungal elements frequently appeared as dark cells, suggesting an increased proliferation activity. Spinous keratinocytes facing intraepidermal microabscesses containing fungal elements showed an abnormal accumulation of tonofilaments and further early keratinization in the spinous cell layer. All of the morphological changes of the dermis and epidermis are regarded as defence reactions against the fungi existing in the skin lesions. There is a close relationship between tissue reactions and morphological changes of fungi in chromoblastomycosis.
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  • 63
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    Archives of dermatological research 284 (1992), S. 275-282 
    ISSN: 1432-069X
    Keywords: Cherry haemangioma ; Type IV collagen ; Type VI collagen ; Immunohistochemistry ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The capillaries in cherry haemangiomas show perivascular hyalinized sheaths. In order to clarify the nature of this sheath material, the extracellular matrix of cherry haemangiomas from 20 normal volunteers (age range 30–64 years) was investigated using immunohistochemical and electronmicroscopical methods. Antibodies against collagen types III, IV and VI and laminin were used. Hyaluronic acid was visualized using the hyaluronic acid binding region of the cartilage proteoglycan as ligand. Electronmicroscopically, the sheaths contained multilaminated basement membrane-like material, collagen fibres 20–25 nm thick with a periodicity of 67 nm and broad-banded aggregates with a periodicity of 100 nm (zebra bodies or fibrous long-spacing fibres). Immunohistochemically, type IV collagen was stained throughout the whole sheath material. Staining for laminin was more confined to the endothelial side of the sheath. Intense staining for type III collagen and hyaluronic acid was found in the connective tissue of the subpapillary layer and between the cherry haemangioma capillaries. Much weaker staining for type III collagen and no staining for hyaluronic acid were found invariably in an area 4–10 Μm thick directly around the capillaries. Both sheath material and intercapillary connective tissue of the haemangiomas showed pronounced staining for collagen type VI. Immunogold staining revealed that type VI collagen was localized to microfibrils 5–6 nm thick and to the broad-banded aggregates with 100 nm periodicity. These findings further underline the assumption that the broad-banded aggregates consist of type VI collagen.
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  • 64
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    Diabetologia 35 (1992), S. 517-521 
    ISSN: 1432-0428
    Keywords: Rat ; teratology ; diabetic pregnancy ; mandible ; congenital malformation ; proteoglycans ; proteoglycan synthesis ; chondroitin sulphate ; costal cartilage
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Fetuses from normal and manifestly diabetic rats were obtained on pregnancy day 20. The fetuses from the diabetic rats were of normal or malformed morphology. Three tissue groups were dissected free; costal cartilage, the hard tissue of the rear, and of the frontal portion of the mandible. These tissues were maintained in vitro for 24 h during which time they were labelled with [35S]sulphate. After the culture period the tissues were extracted with guanidine HCl and the resulting residues were further extracted with alkali. The culture medium was saved and its macromolecular content was compared to that of the extracts. The proteoglycans recovered in all extracts eluted at two distinct positions after chromatography on a Sepharose CL-2B column (peak I: Kav ∼0.4, and peak II: Kav ∼0.8), but the elution patterns were markedly different in extracts from various tissues. Thus, in rib cartilage, the majority of the labelled proteoglycans were located in peak I (∼90%) with no difference between extracts of fetuses from normal and diabetic pregnancies. In extracts of mandibular cartilaginous tissue from normal rat off-spring the peak I percentage (60–80 %) was lower than in the rib cartilage extracts. In the extracts from the frontal portion of malformed mandibles of fetuses of diabetic rats, the peak I percentage (35±21%) was the lowest of all recorded and the only one to significantly differ from the other percentages in its (the frontal mandible) group. The results show an association between a congenital malformation, micrognathia, and a disturbance in the production of chondroitin sulphate proteoglycans in the malformed region.
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  • 65
    ISSN: 1432-0428
    Keywords: Rat ; basal hyperglycaemia ; insulin action ; Type 2 (non-insulin-dependent) diabetes mellitus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We aimed to assess prandial responses, basal glucose turnover and insulin action (euglycaemic clamp) in a very low-dose neonatal streptozotocin model of Type 2 (noninsulin-dependent) diabetes mellitus. Male Wistar rats were injected at 2 days of age with 45 mg/kg streptozotocin or vehicle (control). At 8 weeks, the groups were subdivided and fed either a high-fat or high-starch diet for 3 weeks. Both the fat diet and streptozotocin treatments had independent hyperglycaemic effects (streptozotocin/fat 9.3±0.3 mmol/l; streptozotocin/starch 7.5±0.3 mmol/l; control/fat 7.4±0.1 mmol/l; all p〈0.01 vs control/starch 6.4±0.1 mmol/l). The fat diet effect was associated with both a reduction in basal glucose clearance (p〈0.001) and in basal hepatic glucose output (p〈0.05). Streptozotocin increased basal hepatic glucose output. Significantly higher prandial glycaemia in the streptozotocin/starch group occurred despite similar insulin levels and appeared to be related to an impaired early insulin response. Whole-body and tissue-specific insulin sensitivity were significantly depressed in fat-fed animals compared to starch-fed animals, however there were no significant effects of streptozotocin treatment. We conclude that fasting hyperglycaemia associated with abnormalities in both glucose production and clearance can exist in the presence of a basal hepatic glucose output which is reduced compared to control animals. Furthermore, dietary-fat-induced insulin resistance is not exacerbated by the relative insulin deficiency and/or mild hyper glycaemia observed when dietary fat and neonatal streptozotocin-treatments are combined.
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  • 66
    ISSN: 1432-0428
    Keywords: Rat ; diabetes mellitus ; insulin ; blastocyst ; pre-implantation development
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Pre-implantation embryos were recovered from control, diabetic and insulin-treated diabetic rats on day 5 of pregnancy. Compared to control animals, diabetic rats had a 20 % reduction in the number of embryos per rat and blastocysts recovered from diabetic rats showed a 19 % decrease in total cell number. The cellular decrease observed in blastocysts was mainly at the expense of the inner cell mass. Insulin replacement therapy was started on day 1 of pregnancy and normalized the glycaemia of diabetic rats but failed to raise the number of embryos per rat toward the control value. Insulin treatment, however, fully restored the normal cell number in both the inner cell mass and trophectoderm of blastocysts. The dead cell index, which was significantly elevated in the inner cell mass of blastocysts from diabetic rats, also returned to the control value following insulin treatment. Our data suggest that diabetes-induced impairment of pre-implantation development can be partly prevented by insulin treatment started shortly after conception.
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  • 67
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    Calcified tissue international 51 (1992), S. 137-142 
    ISSN: 1432-0827
    Keywords: Swimming exercise ; Bone histomorphometry ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary To specify the exercise-induced changes on different skeletal sites, the effect of a 5-week endurance swin training was studied in rats. Eighteen Lyon strain (Sprague-Dawley) 5-week old female rats were divided into nine sedentary and nine swimming rats. Each swim training session was increased by 15 minutes from 2–6 hours per day. A histomorphometric study was performed at the primary and secondary spongiosa of the distal femur and at the secondary spongiosa of lumbar and thoracic vertebral bodies. After training, bone loss was observed in the secondary spongiosa of lumbar vertebral bodies (24.7%) and in the primary spongiosa of distal femur (15.2%). A tendency to bone loss was also detected in the secondary spongiosa of distal femur (10.8%), whereas no change was detected in thoracic vertebral bodies. In secondary spongiosa, bone loss was accompanied with a thinning of trabeculae. Total eroded surfaces and osteoid surfaces were significantly decreased in the three studied skeletal sites, suggesting a decreased bone turnover. The decreased thickness of osteoid seams in both lumbar vertebrae and distal femur could mean that the osteoblastic activity has also been altered at the cell level, leading to thinning of trabeculae. Five-week swim training with such duration and intensity of exercise appears unable to increase bone volume in rats and, therefore, causes adverse effects. The three studied bones seemed to adapt differently to experimental conditions. The lack of ground reaction forces induced by water immersion might have contributed to the observed bone loss. “Normal” gravity would be an important cofactor in the osteogenic effects of exercise.
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  • 68
    ISSN: 1432-0827
    Keywords: Cortisol ; Cortical bone ; Bone biomechanics ; Rat ; Femur
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary Doses of 8, 16 (low), 32, 48, 64 (medium), and 150 (high) mg/kg/day of cortisol were administered to groups of 8 growing rats each during 16 days, and their femurs were then submitted to 3-point bending tests at low strain rate. Low doses had no effect. Medium doses, previously shown to improve calcium (Ca) balance and weight gain in the species, augmented diaphyseal elastic and ultimate strength, stiffness, and plastic-to-elastic deformation ratio with respect to untreated controls. This effect was achieved either by enhancing bone mass (volume, sectional moment of inertia, wall/lumen ratio) without changes in material quality parameters (32 mg/kg/day) or, conversely, by increasing bone tissue mechanical properties (stress, modulus of elasticity) not affecting bone geometry (48 and 64 mg/kg/day). The highest dose, known to depress Ca balance and weight gain, impaired diaphyseal mechanical performance in controls by substantially reducing bone mass without major variation in bone material properties, that is, developing a true osteopenic state in mechanical terms. The energy elastically absorbed per unit volume (proportional to the risk of comminute fractures) was greater with the highest dose because of enhanced deformability and diminished bone mass. The biphasic dose-response curves obtained, grossly parallel to those previously demonstrated for metabolic actions of cortisol in the same species, showed that biomechanical repercussion of this treatment on bone depends on different, dose-dependent effects which vary independently in temporal course, intensity, and sign.
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  • 69
    ISSN: 1432-0827
    Keywords: Bone alkaline phosphatase ; Rat ; Vitamin D ; Sorbitol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary In the femoral extremities of the adult rat containing the metaphysis, the epiphyseal cartilage, and the epiphysis, four alkaline phosphatase (AP) forms were distinguished on polyacrylamide gel electrophoresis. Two soluble forms were present in the 160,000 g supernatant: one of Mr 165 kDa and another of Mr 110–115 kDa, which exhibited a strong catalytical activity. Moreover, from the pellet, three membrane-bound forms of Mr 130, 110–115, and 100 kDa could be extacted with sodium deoxycholate. When denaturated AP was visualized by postelectrophoretic autoradiography of the phosphorylated intermediates, subunits always appeared as three monomers of Mr 75–80, 60–70, and 50–60 kDa. As four native forms but only three types of subunits were found to be present in the femur, it seems that, apart from homodimers, some heterodimers could also occur. Three types of diets were administered to three groups of rats for 5 weeks. Two are known to disturb bone mineralization: (1) a vitamin D3-deficient diet, and (2) the same as (1) but enriched with 12% sorbitol. The third was a normal diet containing vitamin D3. Concerning the effects on AP of dietary sorbitol and the vitamin D3-deficient diet, it was found that rats receiving the diet supplemented with sorbitol showed a substantial rise in the activity of the Mr 165 kDa form with the concomitant appearance of a new monomer of Mr 100 kDa. In contrast, rats fed the vitamin D3-deficient diet always displayed an increase in enzyme activity, principally of the Mr 100 and 110 kDa forms. In conclusion, the femur extracts of normal rats contained different forms of AP: either soluble 110–115 and 165 kDa forms or membrane-bound 130, 110–115, and 100 kDa forms. The administration of sorbitol-enriched diet induced a marked increase of the 165 kDa form whereas the administration of vitamin D3-deficient diet increased the 100 and 110 kDa forms.
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  • 70
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    Calcified tissue international 51 (1992), S. 30-34 
    ISSN: 1432-0827
    Keywords: PTHRP ; Anabolic ; Rat ; Bone ; Potency
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary Parathyroid hormone-related protein (PTHRP) has recently been purified from human tumors associated with the syndrome of humoral hypercalcemia of malignancy. The gene encoding PTHRP has been cloned, and based on predicted amino acid sequence, polypeptides comprising the first 36 [36Tyr(1–36) PTHRP amide] and 74 [(1–74)PTHRP] amino acids have been synthesized. Human (h) PTHRP (1–36) and (1–74) are potent bone-resorbing agents, and are catabolic for bone in vivo when given continuously at high doses. Bovine parathyroid hormone (bPTH) (1–34) is also catabolic for bone at high dose levels, but when given in low doses for weeks to months, it is anabolic. Although PTHRP possess several PTH-like properties in bone, hPTHRP (1–34) is reported to be only weakly anabolic in vivo. As polypeptide length influences PTHRP action, we evaluated hPTHRP(1–74) as an anabolic agent for bone in vivo. Twenty-four 4-week-old male Sprague-Dawley rats were given daily subcutaneous injections of hPTHRP(1–74) (1 and 2 nmol/100 g body weight, bw), bPTH(1–34) (4 nmol/100 g bw) or vehicle. Rats were sacrificed on day 12, and serum calcium, phosphorus, and 1,25 dihydroxyvitamin D and femoral bone dry weight, calcium content, and hydroxyproline content were measured. Serum calcium and phosphorus were equivalent in all groups. A significant increase in dry bone weight was observed in both PTHRP-treated groups compared with controls. PTHRP also caused a significant, dose-dependent increase in bone calcium and hydroxypro-line content. Results of these studies indicate that PTHRP (1–74) is anabolic for bone in vivo when administered at low-dosage levels for a prolonged period.
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  • 71
    ISSN: 1432-1335
    Keywords: Renal pelvis ; Carcinogenesis ; 2,2-Dioxopropylnitrosamine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The carcinogenicity of 2,2-dioxopropylnitrosamine on the urinary tract was investigated in three experimental groups of Sprague-Dawley rats (15 males, 15 females/group) by weekly subcutaneous administration for the life of the carcinogen at dose levels 1/5, 1/10 and 1/20 of the LD50, and compared with that in a similar group of untreated controls. It resulted in the induction of urinary tract tumours in 42 out of 79 effective animals (53%). Of these animals, 38 developed tumours within the renal pelvis. In the high-dose group, females had a 100% incidence of renal pelvic tumours, and males 73%. In all experimental groups, renal pelvic tumours were more frequent than ureteral and vesical ones. Histologically, the tumours were transitional cell papillomas and carcinomas, except for one squamous carcinoma. Out of 66 tumours, 42 (64%) were low-grade. High-grade tumours arose mainly in the renal pelvis of animals belonging to the highest-dose group. This experiment offers a useful model for the study of mechanisms involved in renal pelvic carcinogenesis.
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  • 72
    ISSN: 1432-1106
    Keywords: Endothelin ; Ischemia ; Striatum ; Microdialysis ; Cerebral blood flow ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The present study examines the possibility that lesions induced by intrastriatal injections of endothelin-1 (ET-1, 0.43 nmol/0.5 µl) are ischemic in nature due to a vasoconstriction of the cerebral microvessels. In time course and dose-response experiments with ET-1 and in comparisons with ET-3, the volume of the lesions has been determined based mainly on the disappearance of striatal nerve cells, using a computer assisted morphometrical analysis. The blood flow in the neostriatum close to the site of injection of ET-1 was determined acutely by Laser-Doppler flowmetry. The acute metabolic effects of ET-1 were also studied on striatal superfusate levels of lactate, pyruvate, dopamine and its metabolites DOPAC (3,4-dihydroxyphenylacetic acid) and homovanilic acid (HVA) using an instrastriatal microdialysis probe. Dose related striatal lesions were observed with ET-1 (0.043–0.43 nmol) with a peak lesion volume after 24–48 h and the possible existence of a penumbra area. ET-3 showed a reduced potency to produce striatal lesions compared to ET-1. The lesions induced by ET-1 were prevented by coinjection with dihydralazine, a vasodilator drug. Acutely ET-1 (0.43 nmol/0.5 µl) produced a prolonged reduction of the cerebral blood flow down to 40% of control values and temporary increases of striatal lactate and DA efflux, the latter change being very marked. Also a significant reduction of DOPAC and HVA was observed. These neurochemical changes were all prevented by treatment with dihydralazine. These results indicate that ET-1 injected in the neostriatum may produce lesions by causing local ischemia, related to its vasoconstrictor activity and possibly also to an activation of ET-1 receptors in the astroglial-endothelial complex. Based on the present results it seems possible that ET-1 may participate in the multifactorial pathogenesis of cerebral ischemia.
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  • 73
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    Experimental brain research 88 (1992), S. 199-203 
    ISSN: 1432-1106
    Keywords: Visual part of nucleus reticularis thalami ; Unit activity ; Conditioning ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In urethane anesthetized rats neuronal responses of the visual part of nucleus reticularis thalami (vTR) to light were compared with those during pairing light as a conditioned stimulus (CS) with the electrical stimulation of the rat's tail (US). The intensity of the US was adjusted to the minimum required to evoke a slight freezing behavior in the awake rat. The firing rate of most vTR neurons decreased in the period between light and US application (P 〈 0.01). Significant response modulations to light were observed in 39% of the units, in most of them they persisted over an extinction period of 15 min. In addition, neurons which were predominantly inhibited by conditioning sometimes changed from regular spiking to a burst pattern. The results support the hypothesis that conditioning related facilitation of geniculate neurons observed in previous experiments can be explained at least partly by disinhibition of geniculate units from vTR.
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  • 74
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    Experimental brain research 88 (1992), S. 345-354 
    ISSN: 1432-1106
    Keywords: Neuronal subsets ; Pericellular antigen ; Monoclonal antibody ; Cat ; 301 ; VC1.1 ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We reported earlier that monoclonal antibodies (MAbs) 473 and 376 gave perineuronal staining of different subsets of central neurons, and that both immunoreactivities were labile to treatment with chondroitinase ABC. On the other hand, MAb 1B5, the immunoreactivity to which is uncovered by chondroitinase ABC, stained a neuronal subset that included neurons positive to MAbs 473 and 376 (Fujita et al. 1989). We now report a new antibody, MAb 374, that stained perimeter of neurons of a subset different from those stained by MAbs 473, 376 and 1B5. In the rat central nervous system MAb 374-positive cells were found in the neocortex, thalamic reticular nucleus, hippocampus, cerebellar cortex and nuclei, and in the brain stem. MAb 374-immunoreactive neuropil was found in the medial habenular, arcuate, dorsal endopiriform nuclei, and the two plexiform layers of the retina. The immunoreactivity was not affected by treatment with chondroitinase ABC. Immunoblot experiments using a rat brain homogenate revealed a specific band at a position corresponding to a molecular weight of 600 kD.
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  • 75
    ISSN: 1432-1106
    Keywords: Tectogeniculate projections ; SP ; VIP ; CCK ; WGA-HRP ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Substance P (SP)-, vasoactive intestinal polypeptide (VIP)-, and cholecystokinin (CCK)-like immunoreactive (LI) neurons were found in the superior colliculus (SC) of the rat, and examined to ascertain whether they sent projection fibers to the dorsal lateral geniculate nucleus (LGNd). Immunocytochemical staining with antisera against SP, VIP, and CCK showed that many immunoreactive neuronal cell bodies were located in the superficial layers of the SC, especially in the stratum griseum superficiale. The pattern of distribution of these immunoreactive neuronal cell bodies in the SC was similar to that of neuronal cell bodies which were retrogradely labeled with WGA-HRP (wheat germ agglutinin-horseradish peroxidase conjugate) injected ipsilaterally into the LGNd. On the other hand, SP-, VIP- and CCK-LI axons were seen most densely in the lateral part of the LGNd, especially in the small-celled LGNd zone adjacent to the optic tract, where anterograde labeling was also observed after injection of WGA-HRP ipsilaterally into the superficial layers of the SC. When a lesion was produced by kainic acid injection into the superficial layers of the SC, axons showing SP-, VIP-, or CCK-LI in the LGNd ipsilateral to the lesion were markedly depleted. The results indicate that SC-LGNd projection neurons contain SP, VIP, and/or CCK in the rat.
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  • 76
    ISSN: 1432-1106
    Keywords: Basal ganglia ; Pedunculopontine nucleus ; Substantia nigra pars compacta ; Excitatory amino acids ; Acetylcholine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Extracellular single-neuron recordings were obtained from electrophysiologically identified nigrostriatal neurons in chloral hydrate anesthetized rats, in order to test the hypothesis that excitatory amino acid receptors are involved in responses of these neurons to electrical stimulation of the pontine region where the pedunculopontine nucleus (PPN) is located. The effects of iontophoretic application of excitatory amino acids and their antagonists as well as of cholinergic antagonists were tested on the fast orthodromic excitation of nigrostriatal neurons evoked by stimulation of the PPN region. The N-methyl-D-aspartate (NMDA) receptor antagonist D-a-aminoadipic acid as well as the cholinergic receptor antagonists mecamylamine and atropine failed to suppress the synaptic excitation of nigral neurons. The NMDA receptor antagonist DL-2-amino-5-phosphonovalerate exerted a weak depressant action on the synaptic response in a few neurons only. On the contrary, the broad spectrum antagonists of excitatory amino acid receptors kynurenic acid and gamma-Dglutamyl-amino-methyl-sulphonate were found to block simultaneously both the synaptic excitation and the neuronal responses to iontophoretic pulses of glutamate while leaving unaffected the neuronal responses to local application of acetylcholine or carbachol. The competitive antagonist of non-NMDA receptors 6-cyano-2,3-dihy-droxy-7-nitro-quinoxaline suppressed the synaptic excitation at ejection currents which antagonized neuronal responses to quisqualate and kainate. These results suggest that PPN excitatory fibers synapsing onto pars compacta nigrostriatal neurons utilize an excitatory amino acid as a synaptic transmitter acting preferentially on non-NMDA receptors.
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  • 77
    ISSN: 1432-1106
    Keywords: Autoradiography ; Cerebral blood flow ; Cerebral ischemia ; Iodoantipyrine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Cerebral blood flow and histopathological changes after bilateral carotid artery ligation (BCAL) in Wistar rats were studied. Eight of the 38 rats (21%) died within one week. In the 30 survivors, the incidence of histopathological change was 90% in the caudate nucleus, 23% in the cortex, 30% in the hippocampus, and 0% in the other structures. Local cerebral blood flow (LCBF) was measured using the quantitative autoradiographic 14C-iodoantipyrine technique in 24 anatomically discrete regions of the brain. BCAL induced ischemia in the entire forebrain. The percent reduction of LCBF was between 25–94% of the control at 2.5 h after BCAL. LCBF tended to recover 1 week after BCAL except for the regions of neuronal damage. These results suggest that neuronal damage does not correlate with the flow rate. In the present study, selective neuronal damage was also observed in rats with chronic cerebral ischemia.
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  • 78
    ISSN: 1432-1106
    Keywords: Parvalbumin ; GABA ; Nonpyramidal cell ; Monoclonal antibody ; Lectin ; Cerebral cortex ; Proteoglycan ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Monoclonal antibody (MAb) 473 is shown to outline selectively a subpopulation of GABAergic neurons containing a specific calcium-binding protein parvalbumin (PV) in the adult rat parietal cortex, using preembedding immunocytochemistry at the light microscopic level. About 90% of MAb 473 stained cells in the rat parietal cortex were PV immunoreactive. Thus we compared MAb 473 staining with that of three chemical probes, previously shown to stain selectively a subpopulation of PV-containing GABAergic neurons in this brain region, namely, a lectin, Vicia villosa agglutinin (VVA), with a specific affinity for terminal N-acetylgalactosamine, MAb 3B3 which is specific for chondroitin sulfate proteoglycan and MAb HNK-1 which is specific for some types of carbohydrate epitope containing a sulfated derivative of glucuronic acid. About 85% of MAb 473 immunoreactive cells were shown to be stained with VVA. Furthermore about 90% of MAb 473 immunoreactive cells were also stained with MAb 3B3. Thus MAb 473 positive cells were almost included into VVA and/or MAb 3B3 positive cells. On the other hand only about 34% of MAb 473 positive cells were HNK-1 positive, whereas about 44% of HNK-1 positive cells were MAb 473 positive. Thus these two MAbs defined different, though partially overlapping, subsets of PV-containing GABAergic neurons in the rat parietal cortex.
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  • 79
    ISSN: 1432-1106
    Keywords: Noradrenergic hyperactivity ; NE ; ACh ; Fornix section ; DSP4 ; Spatial memory ; Alzheimer's disease ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Rats with unilateral or bilateral partial section of the fornix were impaired on an eight arm radial maze task. Neurochemical analysis of hippocampal tissue four weeks after the lesions revealed a 50% reduction of choline acetyltransferase (ChAT) activity. The cholinergic marker was correlated negatively with the number of errors in the maze; the lower the ChAT activity, the higher the error score. The fornix lesion also induced a 50% reduction in norepinephrine (NE), but no change in the noradrenergic metabolite methylhydroxyphenylglycol (MHPG), suggesting a net increase in turnover of NE in these animals. Additional lesion of the noradrenergic system with the neurotoxin DSP4 reduced both MHPG and NE levels by more than 90%, compared to nonlesioned controls, and reversed the behavioral deficit. This treatment had no further effect on cholinergic markers. There was a significant negative correlation between ChAT activity and the index of NE turnover, suggesting that hyperactivity in the noradrenergic system after fornix section inhibits the spared cholinergic function and thus exacerbates the cognitive deficit. The pattern of neurochemical results bear a striking resemblance to those seen in some Alzheimer's patients and suggest that an equilibrium among neurotransmitters is important to cognitive function.
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  • 80
    ISSN: 1432-1106
    Keywords: GABA ; Iontophoresis ; Somatotopy ; SR95531 ; Ventrobasal thalamus ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We have recently described extensive inhibitory interactions between inputs to the ventroposterolateral (VPL) (Roberts and Wells 1990, 1991) and ventropos-teromedial (VPM) (Salt 1989) portions of the ventrobasal nucleus of the thalamus (VB). We wished to determine whether (i) the inhibition observed in the VPL was operating at the thalamic level, (ii) was dependant on GABA receptors, (iii) was demonstrable on neurons of the ventro-posteromedial nucleus of the thalamus (VPM) and (iv) was operant on test responses evoked by natural stimuli. Conditioning stimulation of sciatic nerve afferents caused inhibition of air jet evoked test responses of single VB neurons in urethane-anaesthetized rats. Both VPM and VPL neurons were subject to inhibition by conditioning stimulation of hindlimb afferents, indicating the widespread nature of the inhibitory process. This inhibition was reduced by the iontophoretic application of SR95531, a GABAA receptor antagonist. We conclude that there is a widely distributed inhibitory system operating in the somatic thalamus which involves both the medial and lateral portions of the nucleus and is, at least in part, mediated by GABAA receptors. The possible involvement of inhibitory processes and intrinsic membrane properties of thalamic neurones in the somatotopic plasticity of the sensory thalamus following deafferentation and in deaf-ferentation pain is discussed.
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  • 81
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    Experimental brain research 89 (1992), S. 459-464 
    ISSN: 1432-1106
    Keywords: Fetal breathing ; Respiratory centers ; Development ; Ontogeny ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A fetal rat brain stem-spinal cord in vitro preparation (15–20 days) which retains for several hours respiratory-like discharges on cervical and cranial ventral roots has been developed for analysing fetal central respiratory activity. Two different patterns of easily distinguishable rhythmic activity were recorded. The first, of spinal origin, appeared every 2–10 min as long bursts of potentials (3–30 s) on cervical, but not hypoglossal, roots. The second pattern corresponded to brief bursts (1 s) of potentials occurring on both cervical and hypoglossal roots at a frequency ranging from 3–4 cycles min-1. The second type of activity was likely to be respiratory since it originated from the medulla, and behaved similarly to the respiratory activity recorded in vitro from newborn rats. The fetal respiratory-like activity was never observed at day 15, appeared at day 16 in 30% of the preparations with fluctuating frequency and amplitude bursts, and stabilised at day 20 where it was usually present and resembled newborn rat respiratory activity: its frequency was stable but was reduced by withdrawal of CO2 and pH stimuli and modulated by a pontine noradrenergic influence. This fetal preparation offers many advantages for studying the ontogeny of the central respiratory activity because of the background knowledge available on the adult and newborn rat respiratory centers and the possibility of performing electrophysiological, morphological and pharmacological fetal studies directly at the central level without any feedback from the periphery.
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  • 82
    ISSN: 1432-1106
    Keywords: Visual system ; Superior colliculus ; Transplantation ; Retinotectal specificity ; Development ; Neuronal phenotype ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Tectal tissue from E15 or E16 Wistar rat embryos was dissociated and reaggregated (DR) prior to transplantation on to the midbrain of newborn host rats. We wished to determine how complete disruption of the donor tissue (i) affected the subsequent morphological development of the grafts in the host brain, and (ii) whether this procedure affected the selectivity with which host retinal axons innervated target regions in the tectal transplants. Forty-three to 135 days after transplantation, host rats received binocular injections of wheatgerm agglutinin-conjugated horseradish peroxidase. After perfusion, frozen sections of the grafts and underlying host brainstem were cut and reacted with tetramethylbenzidine to identify retinal projections, or stained for either acetylcholinesterase (AChE), Nissl or neurofibrils. All host brains contained identifiable DR grafts. Each brain contained at least one large transplant and numerous smaller pieces of graft tissue. The fragmentation of DR grafts was greater than that seen in direct, undissociated tectal transplants; however the morphology of individual DR grafts was markedly similar to direct grafts. Of particular interest was the presence in DR grafts of localized, often oval or circular regions, that possessed high AChE activity and contained mostly small (5 to 10 μm) close-packed neurons. AChE-dense patches were found both superficially and deep within DR grafts and appeared identical to those seen in direct transplants. These regions are thought to be homologous to the superficial, retinorecipient layers of normal superior colliculus (SC) and it is likely that the formation of these localized areas resulted from the selective association of presumptive SGS neurons within the reaggregating neuropil. In almost all cases, host retinal input to DR grafts was confined to the localized AChE-dense patches, suggesting that despite the dissociation procedure, specific retinal innervation of regions containing at least some of the appropriate target cells was maintained in DR tectal grafts.
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  • 83
    ISSN: 1432-1106
    Keywords: Basal forebrain ; Acetylcholine ; Attention ; Transplantation ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Degeneration of the cholinergic magnocellular neurons in the basal forebrain and their cortical projections is a major feature of the neuropathology of Alzheimer's disease. In the present study, two experiments examined the disruptive effects on visual attentional performance of two different manipulations that reduce central cholinergic function. In Expt. I, pharmacological manipulation of the cholinergic system was investigated using icv administration of hemicholinium (HC-3), a 9high affinity choline uptake blocker, administered either alone or in conjunction with the anticholinesterase, physostigmine. The results revealed impairments in the ability of the rats to localize brief visual targets in a serial reaction time task, as shown in particular by a reduction in choice accuracy and lengthening of the latency to respond correctly to the visual stimulus. Cholinergic specificity was supported by the reversal of these behavioural impairments by pre-treatment with the anticholinesterase, physostigmine. In Expt. II, quisqualateinduced lesions of the basal forebrain produced behavioural deficits at 3 weeks post-lesion surgery similar to those observed following icv infusion of HC-3. In an attempt to restore the extrinsic cortical cholinergic innervation by reinnervation of the deafferented cortex, embryonic basal forebrain cholinergic cells were transplanted into the cortex of lesioned animals. After three months recovery, impairments in performance on the baseline schedule of the task were no longer apparent in lesioned animals. However, behavioural deficits, observed predominantly as a lengthening of correct response latency, could be reinstated in the lesioned animals by interpolation of distracting bursts of white noise during each trial, and this deficit was ameliorated by the cholinergic grafts. Furthermore, a non-specific effect of both cholinergic and non-cholinergic grafts in controlling the increase in perseverative time-out responses which occurred as a result of the basal forebrain lesion was consistently observed. These results suggest that cholinergic dysfunction can produce deficits in visual attention which can be ameliorated by cholinergic treatments such as physostigmine or cholinergic-rich cortical grafts. These data provide support for a role for the basal forebrain-neocortical cholinergic projection in attentional function.
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  • 84
    ISSN: 1432-1106
    Keywords: Neural grafting ; Neural transplantation ; Parkinson's disease ; Cryopreservation ; Fetal mesencephalon ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In the present study we quantitatively assessed to what extent freeze-storage at liquid nitrogen temperature influences the survival and function of fetal mesencephalic grafts in the dopamine-depleted rat striatum. Ventral mesencephalic (VM) tissue was dissected from rat fetuses and stored overnight in a preservative medium at 4 °C (hibernation). It was grafted intrastriatally either as a fresh cell suspension or was frozen as tissue fragments or as a cell suspension after stepwise incubation in ascending concentrations of dimethyl-sulphoxide. Following a cryopreservation interval of 80 days in liquid nitrogen, the frozen samples were rapidly thawed, rinsed, and grafted. Cellular viabilities of graft cell suspensions, as assessed by ethidium bromide/acridine orange staining, were decreased from 90% in fresh tissue to 38-35% in frozen and thawed tissue. Amphetamine-induced turning behavior at 6 weeks post-grafting was significantly attenuated in hosts that had received fresh grafts or grafts that were frozen as tissue fragments. Tyrosine hydroxylase-(TH-) immunocytochemistry of recipient brains revealed significant decreases in TH-positive graft cell numbers in rats grafted with cryopreserved tissue (38–42% of fresh tissue). Moreover, the dye exclusion viability of thawed VM tissue was found to accurately predict the subsequent graft survival. There was no difference with respect to graft cell numbers between the two freezing methods employed, though block storage seems to be more simple from a practical point of view. The present study indicates that freezing in liquid nitrogen may be a feasible method for long-term storage of fetal neural tissue for grafting, although a marked decrease in graft survival and function of cryopreserved tissue must be taken into account.
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  • 85
    ISSN: 1432-1106
    Keywords: X-ray irradiation ; GABA ; Catecholamine ; Calcium binding proteins ; Olfactory bulb ; Development ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In the rat olfactory bulb, the majority of interneurons in the glomerular layer (GL) are supposed to be generated during first postnatal week. Low and repeated doses of X-rays (200 rad x 4 and 200 rad x 6) were used during this period to impair the development of interneurons. The resulting effects on olfactory bulb neurons were examined stereologically and immunocytochemically in animals of 4 and 12 weeks of age. Quantitative analysis showed that, 1) the volume of the GL decreased to 55% (1200 rad) – 70% (800 rad) of control, 2) numerical cell densities in GL decreased to 40% (1200 rad) – 60% (800 rad) of control, thus resulting in 3) a decrease of the total cell number in GL to 20% (1200 rad) – 40% (800 rad) of control in irradiated olfactory bulbs of animals 4 weeks old. In comparison, mitral cells, which are generated prenatally, were much less affected (total cell number: 70–80% of control), indicating a selective loss of cells generated during the first postnatal week in GL. Effects on somata and processes immunoreactive for GABA, tyrosine hydroxylase (TH), calbindin D-28K and parvalbumin (PV) were examined in irradiated bulbs of both 4 and 12 week-old rats. All of these immunoreactive elements showed a drastic decrease in all layers. Semiquantitative analysis showed that in the GL, calbindin D-28K immunoreactive (calbindin D-28K(+)) neurons decreased more extensively than TH immunoreactive (TH(+)) and GABA-like immunoreactive (GABA(+)) neurons; that is, TH(+) and GABA(+) neurons decreased to 20% (1200 rad) – 40% (800 rad) of control, whereas calbindin D-28K(+) neurons decreased to 10% (1200 rad) – 30% (800 rad) of control in the GL of irradiated bulbs. These findings indicated that larger proportions of calbindin D-28K(+) neurons might be generated during the first postnatal week than those of GABA(+) and TH(+) neurons. Furthermore, in irradiated bulbs the proportion of GABA(-)TH(+) cells in TH(+) cells increased to about twice of control, and the estimated total numbers of GABA(-)TH(+) cells in irradiated rats were 95% (800 rad) and 40% (1200 rad) of control. These observations suggest that the majority of GABA(-)TH(+) neurons were less affected by X-ray irradiation during the first postnatal week and thus that they might be generated in the prenatal period. Since during the first 2 postnatal weeks, neurons showing GABA(-)TH(+) were not seen in GL (Kosaka et al. 1987a), the majority of GABA(-)TH(+) neurons in adult olfactory bulb were assumed to change their phenotype at some postnatal developmental period.
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  • 86
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    Experimental brain research 90 (1992), S. 147-152 
    ISSN: 1432-1106
    Keywords: Periaqueductal grey matter ; Rostral ventrolateral medulla ; Cardiovascular control ; Medullo-spinal neurones ; Defence reaction ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A study has been carried out to investigate the influence of the periaqueductal grey matter (PAG) on spinally-projecting neurones in the rostral ventrolateral medulla (RVLM) in rats anaesthetised with urethane. Microinjection of D,L-homocysteic acid was used to selectively activate nerve cell bodies in the PAG. Stimulation throughout the rostral half of the PAG and in the caudal PAG on a level with and dorsolateral to the level of the aqueduct evoked excitatory responses in 21 medullospinal cells in the RVLM. The neuronal excitation was associated with a rise in blood pressure. In contrast, stimulation within a restricted area of the ventrolateral PAG at the level of the dorsal raphe nucleus inhibited 10 medullo-spinal neurones in the RVLM, and produced variable changes in blood pressure. Convergence of excitatory and inhibitory influences from dorsolateral and ventrolateral stimulating sites in the PAG on to individual cells was also demonstrated. The results are discussed with respect to the role of the ventrolateral PAG in modulating the cardiovascular components of the “defence” response which is integrated by the dorsal PAG.
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  • 87
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    Experimental brain research 90 (1992), S. 175-179 
    ISSN: 1432-1106
    Keywords: Inferior colliculus ; Spinal cord ; Retrograde transport ; Tyrosine hydroxylase ; Glutamate decarboxylase ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The localization and the transmitter phenotype of subparafascicular thalamic nucleus (Spf) neurons projecting to the inferior colliculus (IC) and to the spinal cord (Sp) were studied by using a retrograde fluorescent double labeling technique, and a combined technique of retrograde tracing and immunohistochemistry for tyrosine hydroxylase (TH) and glutamate decarboxylase (GAD). The cell population of Spf-IC neurons was totally differentiated from that of Spf-Sp neurons which have been reported to be dopaminergic. The former were densely distributed, small to medium sized cells and localized in the central portion of the Spf, while the latter were sparsely distributed, large cells and localized in the marginal portion of the Spf. Spf-IC neurons were completely devoid of TH immunoreactivity and, instead, approximately half of them showed GAD immunoreactivity. From these findings, it is concluded that the Spf is distinctly compartmentalized by the presence at least two separate neuronal subpopulations, which are distinguishable in terms of their cell size, distribution patterns, transmitter phenotypes and trajectories.
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  • 88
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    Experimental brain research 90 (1992), S. 271-274 
    ISSN: 1432-1106
    Keywords: Area postrema ; Lesion ; Supraoptic nucleus ; Oxytocin ; Osmotic stimulation ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Experiments were performed to examine whether or not the area postrema (AP) is involved in the osmotic control of neurohypophysial hormone release. In control rats and in rats bearing extensive lesions of AP, extracellular action potentials were recorded from neurosecretory cells in the supraoptic nucleus (SON) and firing rates determined before and after the intraperitoneal (i.p.) injection of 1.5 M-NaCl solution. Lesion of the AP significantly (p≦0.05, Mann-Whitney's U-test) lowered firing rate of putative vasopressin (phasic) cells but not that of oxytocin (non-phasic) cells. In lesioned animals, i.p. injection of hypertonic saline, however, caused similar changes in plasma osmotic pressure, plasma oxytocin concentration and mean firing rates of both putative oxytocin and vasopressin cells to those in control rats. The results suggest that the osmotic control of SON neurosecretory cell activity in the rat can take place in the absence of the AP.
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  • 89
    ISSN: 1432-1106
    Keywords: Periaqueductal gray matter ; Defensive behavior ; Excitatory amino acids ; Freezing ; Hypertensive reaction ; Ultrasonic vocalization ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In a previous study we investigated the intraspecific defensive reactions evoked by excitation of neurons in the intermediate third of the midbrain periaqueductal gray matter (PAG) of the rat. Experiments revealed that activation of neurons in this region of the PAG mediated: (i) backward defensive behavior, characterized by upright postures and backward movements, and (ii) reactive immobility (“freezing”), in which the rat remained immobile, but reacted with backward defensive behavior to investigative, non-aggressive contact initiated by the partner. In the present study, we aimed to extend our understanding of PAG mediation of defensive behavior by observing: (i) in a non-aggressive social interaction test, the behavioral effects of microinjections of low doses of kainic acid (40 pmol in 200 nl) made in the caudal third of the PAG; and (ii) the behavioral and cardiovascular effects of microinjections of d, l-homocysteic acid (5–10 nmol in 50–100 nl) made in the PAG of the unanesthetized decerebrate rat. Kainic acid injections into the area lateral to the midbrain aqueduct in the caudal third of the PAG evoked: (i) forward avoidance behavior, characterized by forward locomotion and occasional hop/jumps; (ii) reactive immobility (“freezing”), in which the rat remained immobile, but reacted with forward avoidance behavior to investigative, non-aggressive contact initiated by the partner; and (iii) 22–28 kHz ultrasonic vocalizations. These injections also evoked a dramatic increase in defensive responsiveness to tactile stimuli on the half of the body contralateral, but not ipsilateral, to the site of injection. Electroencephalographic measurements indicated that none of these effects were secondary to seizure activity. In the decerebrate rat, d, l-homocysteic acid injections in the caudal third of the PAG evoked forward running movements along with increased blood pressure and heart rate, the strongest effects being evoked from the region lateral to the midbrain aqueduct. More rostrally, sites in the intermediate PAG evoked backward “defensive” movements, which were also associated with increased blood pressure and heart rate. These data, along with those from our previous study in the rat indicate that: (i) defensive reactions are integrated within a longitudinal neuronal column which spans the caudal two thirds of the lateral PAG; (ii) the lateral PAG “defensive behavior” column contains two distinct populations of neurons, one within the intermediate lateral PAG which integrates defensive behavior characterized by facing towards and backing away from a “threatening” stimulus, and a second in the caudal lateral PAG which integrates defensive behavior characterized by forward avoidance behavior; and (iii) neurons within the lateral PAG couple strong cardiovascular changes with each distinctive defensive behavior pattern. The emerging view from this and recent studies of this midbrain region in other species, suggests that similar rostrocaudal differences within a longitudinally oriented lateral PAG neuronal column represent a fundamental principle underlying the PAG organization of defensive behavior.
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  • 90
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    Experimental brain research 90 (1992), S. 469-478 
    ISSN: 1432-1106
    Keywords: Pain ; Nociception ; Spinal cord ; Withdrawal reflexes ; Spinal cord injury ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The spatial organization of the cutaneous input to hindlimb withdrawal reflexes was studied in spinalized, decerebrated, unanesthetized rats. Reflex activity in plantar flexors of the digits, pronators of the foot, dorsiflexors of the digits, and/or the ankle and flexors of the knee was recorded with electromyographic techniques for up to 12 h after spinalization. Graded mechanical (pinch) and thermal stimulation (CO2 laser) of the skin were used. Reflexes were absent (“spinal shock”) during approximately 10–20 min after spinalization. The reflex thresholds for pinch and CO2 laser stimulation then decreased considerably during the following 5–8 h. After this time, even mild pressure (less than 0.1 N/mm2) on the skin was sufficient to evoke a reflex in most muscles. During the period from about 0.5–3 h after spinalization, the nociceptive receptive field of each muscle usually corresponded to the area of the skin withdrawn by the muscle. Maximal responses were evoked from the area of the receptive field maximally withdrawn. During this period, responses to innocuous pinch were evoked mainly from the most sensitive area of the receptive fields. Concomitant with the decrease in reflex thresholds, the nociceptive receptive fields expanded for all muscles, often to include areas of the skin not withdrawn by the muscles. For most muscles, reflexes on tactile stimuli were eventually elicited from the entire receptive fields. The receptive fields for thermonociceptive and mechanonociceptive inputs were similar in most muscles. The interossei muscles were exceptional in that they responded very weakly to thermal stimulation. It is concluded that there are neuronal networks in the spinal cord that translate cutaneous nociceptive and tactile input into a withdrawal. However, the control exerted by descending pathways is necessary to maintain a functionally adequate excitability in these reflex pathways and an appropriate size for their receptive fields.
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  • 91
    ISSN: 1432-1106
    Keywords: Interneuron ; Axo-axonic cell ; Pyramidal cell ; Inhibition ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary During the course of an in vivo intracellular labeling study, a chandelier (axo-axonic) cell was completely filled with biocytin in the CA1 region of the hippocampus. Chandelier cells are known to provide GABAergic terminals exclusively to the axon initial segment of pyramidal cells. The lateral extent and laminar distribution of the dendritic arborization of the chandelier cell was very similar to that of pyramidal cells; the numerous basal and apical dendrites reached the ventricular surface and the hippocampal fissure, respectively. The dendrites, however, had very few spines. The neuron had an asymmetric axonal arbor occupying an elliptical area of 600 by 850 μm in the pyramidal cell layer and stratum oriens, with over three-quarters of the axon projecting to the fimbrial side of the neuron. Counting all clusters of terminals, representing individually innervated axon initial segments, the chandelier cell was estimated to contact 1214 pyramidal cells, a number that exceeds previous estimations, based on Golgi studies, by several-fold. The findings support the view that chandelier cells may control the threshold and/or synchronize large populations of principal cells.
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  • 92
    ISSN: 1432-1106
    Keywords: Opioid peptides ; Neurohypophysis ; Nerve endings ; Vasopressin ; Oxytocin ; Calcium ; Release ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Rat neural lobes and isolated nerve terminals from the neurohypophysis were stimulated in the presence of different opioid agonists and antagonists. The secretion of arginine vasopressin and oxytocin and rise in cytoplasmic calcium induced by depolarization were analyzed by radioimmunoassay and the fluorescent probe fura-2, respectively. The kappa-agonists dynorphin A1 -13 and dynorphin A1 -8 did not affect electrically evoked release of vasopressin, although oxytocin release was slightly reduced. U-50 488, a relatively specific kappa-receptor agonist, had no effect on the amount of vasopressin or oxytocin secreted, although it significantly reduced K+-evoked changes in [Ca2+]i in isolated nerve endings. Two kappa-receptor antagonists, MR 2266 and diprenorphin, alone had no effect on vasopressin and oxytocin secretion from isolated nerve endings depolarized with potassium. Opioid agonists less selective for the kappa receptors, etorphin and ethylketocyclazocin, were found to inhibit the release of both vasopressin and oxytocin significantly. Naloxone, a nonselective opiate receptor antagonist, alone had no effect on vasopressin release but potentiated the electrically evoked release of oxytocin. Naloxone also could overcome the inhibitory effect of etorphin on oxytocin and vasopressin release observed after electrical stimulation of the neural lobe. A number of inconsistencies therefore exist between the effects of opioid agonists and antagonists on neuropeptide release and on the evoked changes in [Ca2+]i. In view of these inconsistencies and the high concentrations of opioid agonists and antagonists necessary to modify release, we conclude that it is doubtful that opioid molecules have a physiological role in controlling neurohypophysial secretion.
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  • 93
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    Experimental brain research 90 (1992), S. 639-642 
    ISSN: 1432-1106
    Keywords: Vibrissae ; Barrels ; Somatosensory cortex ; 2-deoxyglucose ; Neuronal plasticity ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Effects of sensory deprivation upon ability of a vibrissa to activate a functional column in the barrel field of somatosensory cortex were examined with 2 deoxyglucose (2DG) autoradiography in the rat. After six weeks of whisker plucking started at birth, and one week of recovery, the cortical column activated by the deprived whisker and labeled with 2DG had a reduced diameter but higher labeling density than the normal vibrissal column. Loss of a peri-barrel labeling zone, possibly due to loss of intracortical activation, is suggested.
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  • 94
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    Experimental brain research 91 (1992), S. 12-20 
    ISSN: 1432-1106
    Keywords: Choleragenoid ; Horseradish peroxidase ; Lumbar spinal ganglia ; Brainstem nuclei ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Brain stem projections from each of the L1–L6 lumbar dorsal root ganglia (DRGs) were investigated in adult rats following DRG injections of choleragenoid-horseradish peroxidase. All these DRGs projected throughout the rostrocaudal extent of the gracile nucleus (Gr). Labeling from L1–L6 DRGs was transported to successively more dorsomedial areas of Gr. Investigation of the Gr projections from the DRGs revealed a somatotopic organization which was most prominent in the middle part of Gr. The cuneate nucleus showed smaller projections from all investigated DRGs. Minor projections to the internal basilar nucleus, external cuneate nucleus, medial vestibular nucleus, ventral cochlear nucleus and trigeminal sensory nuclei were also found from some of the DRGs.
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  • 95
    ISSN: 1432-1106
    Keywords: Glutamate ; Glutamine ; Cochlea ; Neurotransmitter ; Immunocytochemistry ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The light- and electron microscopic localization of glutamate and glutamine in the rat organ of Corti was studied by means of antisera raised against the respective amino acids coupled to carrier proteins. The light microscopic analysis was performed in semithin sections treated according to the peroxidase-antiperoxidase procedure. The two amino acids were visualized in the same ultrathin sections by use of postembedding immunocytochemistry with two different gold particle sizes. The distribution of aspartate-like immunoreactivity was also recorded, but only at the light microscopic level. In the hair cells, the level of glutamate-like immunoreactivity was higher than that in supporting cells but lower than that in the presumed glutamatergic terminals of cerebellar parallel and mossy fibres. The latter types of terminal were sampled from ultrathin sections that had been incubated under the same conditions as the cochlear sections. Within the hair cells, gold particles signalling glutamate were enriched on mitochondria but not on clusters of synaptic vesicles. Glutamine-like immunoreactivity was present in hair cells as well as supporting cells. The glutamate/glutamine ratio, expressed as the ratio between the respective gold particle densities, was considerably lower for hair cells compared with the cerebellar excitatory terminals. No consistent difference was found between outer and inner hair cells in relation to the levels and subcellular distribution of glutamate and glutamine immunoreactivities. Aspartate-like immunoreactivity was accumulated in outer hair cells, with some labelling also of border cells and Böttcher cells. While the present study confirmed the presence of glutamate in hair cells and demonstrated that these cells are also endowed with the important glutamate precursor glutamine, it revealed notable differences between hair cells and presumed glutamatergic terminals in the CNS. These could reflect differences in the synthesis and compartmentation of transmitter glutamate. Methodological factors could also contribute. Alternatively, the differences could be interpreted to suggest that the hair cell transmitter is not glutamate, but a similar compound. Aspartate could be a candidate in the case of the outer hair cells.
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  • 96
    ISSN: 1432-1106
    Keywords: Hyperalgesia ; Peripheral neuropathy ; Nerve histopathology ; Neuropathic pain ; Unmyelinated fibre ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A mononeuropathy, produced by ligation of the sciatic nerve in rats, has recently been proposed as an animal model of experimental pain and pain-related disorders (hyperalgesia and allodynia). We investigated quantitatively the morphological changes in myelinated and unmyelinated fibres of the sciatic nerves 2 weeks after ligation in rats exhibiting allodynia to thermal stimulation. There was a marked reduction in the number of large myelinated fibres distal to the ligature (711 ± 34 compared with 5315 ± 230 in normal nerves). We also found a significant loss of small myelinated fibres (2429 ± 109 compared with 3197 ± 308 in normal nerves), the remaining fibres of this type showing pathological properties. Finally, ultrastructural evidence of damage to unmyelinated fibres was found. The typical pattern of large clusters of normal unmyelinated axons was no longer present within most regions of the nerve. There was a significant reduction in the size of the unmyelinated fibres (0.41 μm ± 0.15 compared with 0.71 μm ± 0.08 in normal nerves), together with a twofold increase in their number per cluster. Hypotheses about the mechanism of thermal allodynia in this pain model therefore must take into account the fact that all fibre classes show pathological changes.
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  • 97
    ISSN: 1432-1106
    Keywords: Transplantation ; Developmental neurobiology ; Retrograde labelling ; Immunocytochemistry ; Acetylcholinesterase histochemistry ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Embryonic spinal cord grafts from 12-day-old rat embryos were placed into the lumbar spinal cord of adult rats depleted of sciatic motoneurones by a neonatal nerve injury. A soleus muscle was removed from the leg and implanted paravertebrally, the proximal end of its nerve connected to the graft site. Fluorescent retrograde tracers injected into the soleus implant, 37–64 days postoperatively, labelled neurones that had grown axons to the muscle. Approximately one-fifth of retrogradely labelled neurones were within the graft; however, the majority were found within the host spinal cord close to the graft. These included large neurones within the motoneurone-depleted dorsolateral ventral horn. In control experiments a muscle and nerve were implanted but no embryonic tissue grafted. Significantly fewer neurones were labelled. In some animals, one tracer was injected into the soleus muscle whilst another was applied to the cut sciatic nerve ipsilateral to the graft site. No neurones were found to project axons to both targets. In animals that received grafts prelabelled with bromodeoxyuridine (BrDU) some neurones were found to be both BrDU positive and retrogradely labelled from the soleus implant. These were most frequently within the motoneuronedepleted ventral horn ipsilateral to the graft. Thus, grafted neurones may migrate to an appropriate location within the host neuropil. Acetylcholinesterase (AChE) histochemistry showed the graft site contained immature but AChE-positive neurones. Some regions of host ventral horn contained unusually few AChE-positive nerve fibres and occasional large AChE-positive neurones, some of which were also retrogradely labelled from the implanted muscle. Studies of implanted soleus 21–90 days after transplantation showed that muscle fibres, after initial degeneration, regenerated displaying differing phenotypes, presumably under the influence of new motor innervation.
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  • 98
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    Experimental brain research 91 (1992), S. 415-424 
    ISSN: 1432-1106
    Keywords: Taste ; Insular cortex ; Response profile ; Inhibitory response ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The responses of 84 taste neurons to stimulation of the oral cavity in rats were examined; most taste neurons were found in either a granular insular area (area GI; n = 55) or dysgranular insular area (DI; n = 25), and the others (n = 4) were in an agranular insular area (area AI). The fraction of neurons responding to only one of the four basic stimuli was significantly larger in area GI than in area DI. When neurons were classified by the stimulus which most excited the neuron among the four basic stimuli, every “best-stimulus category” of neurons was found in both GI and DI areas. Quinine-best and “multistimulus-type” neurons, whose responses to some non-best stimulus exceeded 90% of the maximum, were more numerous in the cortex than in the thalamocortical relay neurons. When responses were plotted against taste stimuli arranged in the order of sucrose, NaCl, HCl, and quinine along the abscissa (taste coordinate), response profiles of taste neurons often showed two peaks. The double-peaked type of response profiles were found in every best-stimulus category of neurons in both areas; though, a significantly large fraction of quinine-best neurons in area GI were of the double-peaked type. Some taste neurons in area GI (n = 21) and in area DI (n = 7) were inhibited by one to two taste stimuli, particularly by the stimuli present next to the best one along the taste coordinate. In correlation profiles — correlation coefficients between sucrose and NaCl and between HCl and quinine — pairs of stimuli which were located next to each other on the taste coordinate were significantly smaller in area GI than in area DI. It is thus highly probable that area GI plays an important role in fine taste discrimination and area DI in integration of taste information.
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  • 99
    ISSN: 1432-1106
    Keywords: Cervical ; Cuneate ; Trigeminal ; Primary afferents ; Somatosensory ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Experiments were performed on rats to determine whether primary afferents from the upper cervical region terminate directly on Spinothalamic and propriospinal neurones. The central terminations of primary afferents from the upper cervical region were identified by diffusely filling their axons with horseradish peroxidase. Spinothalamic neurones or propriospinal neurones were identified in the same experimental animals by using retrograde transport of wheat germ agglutinin conjugated to horseradish peroxidase. Approximately 3–11 % of Spinothalamic cells in laminae 4–6 of spinal segments C2–4 received apparent synaptic contacts from primary afferents on the soma or primary dendrites. Approximately 18–36% of propriospinal neurones with axons descending to lower thoracic or lumbar levels received apparent synaptic contacts on the soma or primary dendrites. These data provide anatomical evidence that Spinothalamic and long propriospinal neurones in the upper cervical cord are excited directly by primary afferents. The data also help to clarify the neural circuitry underlying somatic sensation and reflex movements evoked by neck receptors.
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  • 100
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    Experimental brain research 88 (1992), S. 33-40 
    ISSN: 1432-1106
    Keywords: Corpus callosum ; Frontal agranular cortex ; GABA receptor ; NMDA receptor ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A slice preparation of rat frontal agranular cortex preserving commissural inputs has been used for intracellular recording from layer V pyramidal cells, in order to characterize the synaptic potentials induced by stimulation of the corpus callosum and to reveal the subtypes of amino acid receptors involved. Stimulation of the corpus callosum induced EPSPs followed by early IPSPs with a peak latency of 30 ± 2 ms and late IPSPs with a peak latency of 185 ± 18 ms. Reversal potentials for early and late IPSPs were −75 ± 5 mV (early) and −96 ± 5 mV (late). Late IPSPs were more dependent on extracellular K+ concentration. The early IPSPs were blocked by GABAA antagonists, bicuculline and picrotoxin, whereas the late IPSPs were reduced by the GABAB antagonist, phaclofen. CNQX (6-cyano-7-nitroquinoxaline-2,3-dione), an antagonist of non-NMDA (N-methyl-D-aspartate) receptors, suppressed both EPSPs and late IPSPs at 5 µM. Early IPSPs remained at this concentration but were suppressed by 20 µM CNQX. In Mg2+-free solution, EPSPs were larger and more prolonged than in control solution. These enhanced EPSPs persisted after 5 to 20 µM CNQX, but were reduced in amplitude, and their onset was delayed by 3.6 ± 0.8 ms. The remaining EPSPs were suppressed by 50 µM APV (DL-2-amino-5-phosphono-valeric acid), an antagonist of NMDA receptors. In Mg2+-free solution containing 5 to 20 µM CNQX, the late IPSPs were not diminished. The remaining late IPSPs were suppressed by APV or by phaclofen. By contrast, the amplitude of early IPSPs was not affected by APV in Mg2+-free solution containing 5 µM CNQX. These results show that stimulation of the corpus callosum can induce GABAA and GABAB dependent IPSPs and NMDA and non-NMDA dependent excitation. It is suggested that these four types of amino acid-based transmission are conveyed by intracortical pathways with different characteristics.
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