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  • 1985-1989  (226)
  • 1975-1979
  • 1800-1809
  • 1988  (226)
  • Rat  (167)
  • Electron microscopy
  • 1
    ISSN: 1437-2320
    Keywords: Electron microscopy ; ependymoma ; glycogen ; ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We report our results on the ultrastructure of 21 ependymomas and establish the following diagnostic criteria: 1. Glycogen is the most frequently encountered criterion, followed by desmosomes, cilia, basal bodies and microvilli. Fifteen tumors had 3 or more of these features. 2. The allegedly typical nuclear pattern was found in only 6 cases. 3. Special ultrastructural features seen include basement membranes in a mid-thoracic ependymoma. Furthermore we propose the hypothesis that glycogen might be involved in cilia assembly.
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 337 (1988), S. 1-8 
    ISSN: 1432-1912
    Keywords: 5-Hydroxytryptamine ; 5-HT receptors ; 5-Carboxamidotryptamine ; Rat ; Cardiovascular
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Peripheral 5-HT receptor-mediated responses were examined in pithed spontaneously hypertensive rats and normotensive wistar rats. Responses examined were: Pressor and depressor responses, tachycardia and inhibition of stimulation-evoked tachycardia. In pithed spontaneously hypertensive rats, 5-HT, but not the 5-HT1-selective agonist 5-carboxamidotryptamine, produced pressor responses, and these were potently antagonised by the 5-HT2-selective antagonists ketanserin and LY 53857. In pithed spontaneously hypertensive rats, the tachycardia to 5-HT was abolished by a combination of the 5-HT2 receptor antagonist LY 53857 and propranolol, suggesting that the tachycardia is mediated by 5-HT2 receptors and by release of noradrenaline. In pithed spontaneously hypertensive rats, 5-carboxamidotryptamine, 5-HT, and to a lesser extent the 5-HT1 receptor agonist RU 24969, but not the 5-HT1A receptor agonist 8-OH-DPAT, produced depressor responses which were antagonised by methysergide and metitepin, but which do not clearly fit with any of the 5-HT, ligand binding sites. In pithed normotensive wistar rat, 5-carboxamidotryptamine was approximately 100 times more potent than 5-HT and 8-OH-DPAT at inhibiting the cardio-acceleration produced by single pulse electrical stimulation and this inhibition was antagonised by metitepin, so that the response is mediated by 5-HT1 receptors.
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 337 (1988), S. 164-168 
    ISSN: 1432-1912
    Keywords: Central nervous system ; Alpha-2 adrenoceptors ; Oxymetazoline ; Vagus nerve ; Pituitary gland ; Vasopressin ; Gastric secretion ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The mechanism of the gastric antisecretory action of the stimulation of central alpha-2 adrenoceptors were studied in conscious, pylorus-ligated rats using intracerebroventricularly (i.c.v.) administered oxymetazoline as the model substance. I.c.v. administration of 10 μg of oxymetazoline strongly inhibited the secretion of acid, pepsin and fluid, whereas upon s.c. injection this dose was without any effect. Pretreatment with idazoxan abolished the antisecretory effect of i.c.v. administered oxymetazoline. I.c.v. injected oxymetazoline inhibited gastric secretion induced by carbachol in vagotomized rats, but the inhibitory effect was less pronounced than on the spontaneous secretion in rats with intact vagi. Hypophysectomy abolished the antisecretory effect of i.c.v. oxymetazoline, and pretreatment with the vasopressin antagonist, d(CH2)5Tyr(Me)AVP, significantly attenuated it. The results suggest that the inhibition of gastric secretion by the stimulation of central alpha-2 adrenoceptors in rats is mediated in part by vasopressin released from the pituitary gland.
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  • 4
    ISSN: 1432-1912
    Keywords: Calcitonin gene-related peptides ; Tachykinins ; Capsaicin ; Cardiac sensory nerves ; Rat ; Guinea-pig
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 1. The effects of calcitonin gene-related peptide (CGRP), neurokinin A (NKA), neuropeptide K (NPK) and substance P (SP) on contractility of the guinea-pig and rat heart were studied in vitro in relation to the response to capsaicin. 2. Human (h) CGRP alpha (a) and beta (β) were equipotent in stimulating the contractile force and rate of the spontaneously beating guinea-pig right atrium. 3. Both NKA and NPK inhibited contractile force and rate in the guinea-pig atrium whilst a mainly negative chronotropic effect was observed in the whole heart. SP did not influence cardiac contractility. 4. Human CGRP α and β mimicked the contractile effects of capsaicin in the guinea-pig atrium. In the whole heart preparation, hCGRP α and capsaicin increased heart rate whereas capsaicin also evoked an atropine-resistant inhibition of contractile force. The stimulatory effect of capsaicin on heart rate was absent after systemic capsaicin pretreatment, while the inhibition of ventricular contractile tension remained unchanged. 5. Extended incubation with hCGRP α or β was associated with development of cross-tachyphylaxis between these two agents in the guinea-pig atrium. However, CGRP tachyphylaxis did not change the atrial response to noradrenaline, forskolin or NKA. The stimulatory effects of capsaicin on atrial contractility were absent after tachyphylaxis to hCGRP α or β. 6. There was no detectable supersensitivity to the stimulatory effects of rat (r) CGRP α on the spontaneously beating atrium after capsaicin pretreatment of adult or neonatal rats. In conclusion the present data provide further evidence that the capsaicin-induced stimulation of atrial contractility is due to local release of CGRP. CGRP tachyphylaxis seems to be a specific, receptor-mediated event and is not related to down-regulation of the adenylate cyclase system. The inhibition of the contractile force in whole heart preparations by capsaicin is most likely due to a non-cholinergic effect independent of tachykinin release.
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  • 5
    ISSN: 1432-0983
    Keywords: Ribosomal protein ; Immunological homology ; Yeast ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary Polyclonal antibodies raised against ribosomal protein (r-protein) L2 of Schizosaccharomyces pombe were used to check for cross-reaktions with total r-proteins of rat liver. Using this procedure, the rat liver r-proteins, L4 and L24, were identified as being immunologically related to yeast L2. In addtional, homologies between rat liver L4 and L24 were detected. The possible implications for the regulation of r-protein synthesis are discussed.
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Current genetics 14 (1988), S. 163-170 
    ISSN: 1432-0983
    Keywords: Plant mtDNA ; Electron microscopy ; Restriction enzymes ; Hairpin structures
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary Broad bean (Vicia faba) mitochondrial DNA (mtDNA) includes three circular plasmids: mt-plasmid 1 (1,704 ntp), mt-plasmid 2 (1,695 ntp) and mt-plasmid 3 (1,476 ntp). Partially replicated circular forms of these mt-plasmids have been observed in electron microscope preparations. Restriction enzymes that cleave either mt-plasmid 2 (but not mt-plasmids 1 and 3) or mt-plasmid 3 (but not mt-plasmids 1 and 2) were used to generate linear forms of partially replicated mt-plasmid 2 and mt-plasmid 3 molecules. Analyses of these linearized replicative intermediates, observed by electron microscopy, indicated that in both mt-plasmid 2 and mt-plasmid 3 replication originates at a specific location and proceeds in the same, single direction around the molecules. The replication origins of mt-plasmid 2 and mt-plasmid 3 map close to sequences that can fold into hairpin structures.
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Pediatric surgery international 3 (1988), S. 338-342 
    ISSN: 1437-9813
    Keywords: Spleen ; Autotransplantation ; Protective function ; Malaria ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Autologous splenic fragments regenerate after transplantation. The regenerated mass only attains a small proportion of that of the normal spleen. Some data on the protective function are controversial. Malaria parasites were inoculated to test splenic function in rats. Peak parasitemia, the course of parasitemia, and anemia were comparable in normal and autotransplanted rats. In rats with splenic transplants only the duration of the parasitemia was longer than in normal rats. In contrast, splenectomized rats were unable to clear the parasites from the blood and became progressively anemic. After stimulating regeneration by increasing the work load to the white pulp or the macrophage system, more regenerated tissue was found, but the protective function did not increase. The amount of regenerated splenic tissue does not correlate with its protective function.
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  • 8
    ISSN: 1432-2307
    Keywords: Mammary neoplasms ; DMBA ; Rat ; Carcinoma ; Sarcoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Mammary tumours were induced by the direct dusting of 1 mg, 7,12-dimethylbenz(a)anthracene (DMBA) powder onto the mammary gland of both 30-day-old female and male Sprague-Dawley rats, and the tumours were examined histologically. Mammary tumours developed in 43/43 (100%) of the females 11 to 20 weeks after DMBA dusting and 16/23 (70%) of the males 18 to 28 weeks after dusting, while non-mammary spindle cell sarcomas occurred in 5/23 (22%) of the males 15 to 24 weeks after dusting. A variety of benign and malignant mammary tumours of epithelial and/or mesenchymal origin were induced, which are comparable to human mammary tumours. Different histological patterns were observed in different areas of the same tumours. Ovariectomy revealed hormone (ovary)-dependency in 10/17 (59%) of the tumours, revealing regressing epithelial and proliferating mesenchymal tumour elements on histological examination.
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Virchows Archiv 414 (1988), S. 77-81 
    ISSN: 1432-2307
    Keywords: Epithelium ; Intestine ; Desquamation ; Restitution ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In situ loops of large bowel of anaesthetised rats were used to observe epithelial restitution following surface desquamation using solutions of bile salts. The treatment induced complete surface desquamation but no disruption of the basal lamina. There was evidence of, cell migration at 30 min, and a complete surface epithelium two h post treatment. Neither a continuous contact between migrating cells and the basal lamina, nor a complete covering of secreted mucus, appeared necessary for epithelial restitution to occur.
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  • 10
    ISSN: 1432-2307
    Keywords: Neuroectodermal bone tumours ; Immunochemistry ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Peripheral neuroectodermal tumours (PNET) of bone are rare and mimick those seen in soft tissue (peripheral neuroepithelioma of soft tissue). Their differential diagnosis from Ewing's sarcoma (Es) is extremely difficult by optical means. Here we report 14 new cases of PNET of bone (other than Askin's neoplasm) located primarily in the limbs, pelvic girdle and scapula. Clinically and radiologically they displayed Ewing's sarcoma-like features: mean age was 14.4 years, male/ female ratio being 3:11. Metastasis was present in 6 cases at diagnosis (5 with bone metastasis). Prognosis was poor; thirteen patients died; only one with a metatarsal located tumour is alive and free of disease. The mean survival rate was 25 months following diagnosis and treatment with radio- and multimodal chemotherapy. Histologically the 14 cases displayed Homer-Wright rosettes and pseudorosette-like structures, as well as a fibrillary background and lobular pattern. Immunohistochemistry revealed positivity in a number of neural markers when using paraffin-embedded material: NSE, B-2-microglobuline, HNK-1 (leu-7) and E-36 antibodies. At EM level the cell cytoplasms evidenced dense-core granules with neurosecretion, neurotubules and intermediate filaments like those seen in peripheral neuroepithelioma.
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  • 11
    Electronic Resource
    Electronic Resource
    Springer
    Virchows Archiv 412 (1988), S. 499-513 
    ISSN: 1432-2307
    Keywords: Alveolar soft part sarcoma ; Cytology ; Electron microscopy ; Immunohistochemistry ; DNA analysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The type, differentiation and histogenesis of the tumor cells of alveolar soft part sarcoma (ASPS) have been analyzed in a series of ten cases by a light-microscopic, ultrastructural, immunohistochemical and cytologic investigation and quantitative DNA analysis. Four tumors deviated from ordinary ASPS: three were wholly or partly of the so-called pleomorphic variant of ASPS and a fourth tumor showed calcifications of the psammoma body type. The ultrastructural findings and immunohistochemical demonstration of desmin supported the hypothesis of a rhabdomyomatous differentiation and gave no support to epithelial (negative immunoreactions for cytokeratins, epithelial membrane antigen, HMFG-1 and -2, tissue polypeptide antigen (TPA)) or neuroectodermal (negative for S-100 protein, glial fibrillary acidic protein, neurofilaments) differentiation. The negative immunoreactions for vimentin and myoglobin and the positive reaction for neuron specific enolase (NSE) do not exclude a rhabdomyomatous differentiation since in rhabdomyosarcomas the undifferentiated rhabdomyoblasts generally contain vimentin and the differentiated tumor cells contain myoglobin and rhabdomyosarcoma has previously been reported as being positive for NSE. The production of external lamina material peripherally in the tumor cell nests and around vessels in the vascular septa was demonstrated both ultrastructurally and by immunohistochemistry using antibodies against collagen IV and laminin. The cytologic appearance in smears obtained by fine-needle aspiration from a case of the pleomorphic variant showed some resemblance to that of a carcinoma. The seven tumors with an ordinary cell appearance were found to show a diploid DNA-distribution at a quantitative analysis performed on paraffin sections, while the three tumors wholly or partly of the pleomorphic type showed an additional tetraploid peak.
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  • 12
    ISSN: 1432-2307
    Keywords: Hairy leukoplakia ; Electron microscopy ; Epstein-Barr virus ; Candida albicans
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Three cases of HL from the lateral border of the tongue of male homosexual AIDS patients were investigated by thin section electron microscopy. Keratinocytes contained condensed chromatin in their pyknotic nuclei and a few organelles in the oedematous cytoplasm. Chromatin was in close association to the nuclear membrane and showed a punched-out appearance. Particles typical of the herpes virus group were abundant in the upper two thirds of the epithelium in all three cases. Virus particles were seen frequently in the nuclei of the ballooned keratinocytes, but rarely in cells containing Candida albicans. Viral nucleocapsids were observed budding at the inner nuclear membrane, thereby acquiring the prospective viral envelope. Complete, enveloped virions were found in the endoplasmic reticulum and in the extracellular space. These virions were identified immunohistochemically as Epstein-Barr virus (EBV) using two monoclonal antibodies directed against EBV capsid and membrane antigen, respectively. Candida albicans was observed in the stratum corneum and in the upper layer of the stratum spinosum. Special cytoplasmic tubular structures arranged in parallel bundles were found in koilocytotic cells in addition to characteristic membrane structures composed of undulating convoluted membranes. Epithelial basement membranes were always intact.
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  • 13
    Electronic Resource
    Electronic Resource
    Springer
    Virchows Archiv 414 (1988), S. 21-27 
    ISSN: 1432-2307
    Keywords: Monoblastic leukaemia ; Electron microscopy ; Morphometry ; Multivariate statistics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Morphometric studies were carried out on five ultrastructural measures of size or quantity of some of the intracellular organelles in monoblasts obtained from six patients diagnosed as having acute monoblastic leukaemia and also on monocytes from six normal controls. The morphometric measures were analysed using a one way multivariate analysis of variance (MANOVA) to see whether acute monoblastic leukaemic cells differed from those of normals. It was found that there was a highly significant decrease both in the surface to volume ratio of mitochondria and also in the surface to volume ratio of the nucleus. The possible physiological significance of these structural changes is stressed.
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  • 14
    Electronic Resource
    Electronic Resource
    Springer
    Virchows Archiv 412 (1988), S. 273-279 
    ISSN: 1432-2307
    Keywords: Osteosarcoma ; Clear cell ; Histopathology ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The reports concerns the light microscopical and ultrastructural findings obtained in three conventional osteosarcomas with an unusually high admixture of clear cells, whose presence appeared to be responsible for the marked change in the histological pattern of these tumours. In the tumours with a prevailing fibroblastic component the clear cells were either irregularly scattered throughout the tumour in the form of small groups, or they formed large groups sharply demarcated against the fusicellular areas of the tumours. In two cases it was shown that their cytoplasm contained exaggerated glycogen deposits accompanied by the formation of glycogen-containing phagolysosomes and occasional empty vacuoles. In the third case the clear cells showed vacuolar degeneration with numerous single-membrane-bound, empty vacuoles. In contrast to the clear-cell chondrosarcoma we did not find S-100 protein in clear cells of our osteosarcomas. Such findings could be particularly significant in the differential diagnosis of bone tumours.
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  • 15
    ISSN: 1432-2307
    Keywords: Electron microscopy ; Morphometry ; Null cell adenoma ; Oncocytoma ; Pituitary adenoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In this study, light microscopic and ultrastructural morphometric features of oncocytomas and null cell adenomas were compared and the morphometric data were correlated with in vitro endocrine activity. All tumours were unassociated with clinical or biochemical evidence of hormone excess and were diagnosed as oncocytomas or null cell adenomas, using histology, immunohistochemistry and electron microscopy. In oncocytomas, when compared with null cell adenomas, light microscopic morphometry revealed that total cell areas were significantly larger and nuclear cytoplasmic ratios were smaller due to an increase in cytoplasmic areas. Ultrastructural morphometry disclosed an abundance of mitochondria in oncocytomas. Absolute volumes of cytoplasmic organelles per cell were not reduced in oncocytomas compared with those of null cell adenomas. These results indicate that accumulating mitochondria do not replace other cytoplasmic organelles, and furthermore that the functional potential of oncocytomas is not lost. In vitro study demonstrated the production of pituitary hormones, primarily gonadotropins in oncocytomas and null cell adenomas. It can be concluded that oncocytomas, which represent the final stage of oncocytic transformation, have a close relationship with null cell adenomas based on morphometric comparison as well as in vitro studies.
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  • 16
    ISSN: 1432-2307
    Keywords: Neuroendocrine differentiation ; Immunohistochemistry ; Electron microscopy ; Small cell undifferentiated bladder carcinoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Small cell carcinoma with the histological appearance of pulmonary small cell carcinoma is a rare tumour in the urinary bladder. In previous case reports the neuroendocrine nature of small cell bladder carcinoma has been accepted, but on review the evidence for true neuroendocrine differentiation appears unsatisfactory. In this study the histological, immunohistochemical and ultrastructural characteristics of three cases of small cell carcinoma of the urinary bladder are described. Ultrastructurally, the cytoplasm of all three tumours contained neurosecretory-type granules and each of the tumours demonstrated positive immunoreaction for two or more neuroendocrine markers, from a panel including neuron-specific enolase, chromogranin A, Leu-7, bombesin and synaptophysin. Although the combination of ultrastructural and immunohistochemical examination obviously offers the strongest evidence in establishing neuroendocrine differentiation, it is argued that immunohistochemistry alone may also yield important information in demonstrating a neuroendocrine nature, provided that at least neuron-specific enolase and synaptophysin are included as markers. The clinical relevance of identifying neuroendocrine differentiation in small cell bladder carcinoma is suggested by the favourable response to combination chemotherapy in two of our cases.
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  • 17
    Electronic Resource
    Electronic Resource
    Springer
    Urological research 16 (1988), S. 127-131 
    ISSN: 1434-0879
    Keywords: Microsurgery ; CO2 laser ; Neodymium Yag laser ; Vascular anastomosis ; Rat ; Tensile strength ; Histology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A comparative study was undertaken to investigate the application of a specially adapted microsurgical Neodymium Yag Laser system with a wavelength of 1,319 μm and a CO2 laser system for laser assisted microvascular end-to-end anastomosis (LAMA) of the rat femoral artery. Conventionally sutured anastomoses served as controls. Postoperative investigations included patency tests, light microscopy and tensile strength measurements. Both laser systems seem to be equally suitable for LAMA: The patency rates do not differ from those of sutured anstomoses and formation of microscopically small aneurysms occurred predominantly in control animals and only once in laser groups. The clamp time needed for LAMA was half the time that was needed for sutured anastomoses. Wound healing in all groups was similar with less fibrotic reactions and less foreign body granulomas in laser groups. At all intervals tensile strength was significantly higher for sutured anastomoses while differences between the CO2- and the ND: Yag-laser groups were not statistically significant. Potential applications in urology include microvascular anastomoses in erectile dysfunction, pediatric and reconstructive urology.
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  • 18
    Electronic Resource
    Electronic Resource
    Springer
    Research in experimental medicine 188 (1988), S. 115-121 
    ISSN: 1433-8580
    Keywords: Gastrin ; Rat ; Somatostatin ; Stomach
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Low concentrations of somatostatin and gastrin within or slightly above the range of physiologically circulating levels were perfused in the isolated, vascularly perfused rat stomach preparation. Somatostatin at 10 and 50 pg/ml significantly inhibited acetylcholine-stimulated gastrin secretion by 26% and 45%, respectively, whereas perfusion of 50 and 500 pg/ml exogenous gastrin did not modify gastric somatostatin secretion. Perfusion of somatostatin-antiserum significantly increased gastrin release by 235%. It is concluded that (1) somatostatin is a powerful inhibitor of the gastrin cell under in vitro conditions; the data are in accordance with a concept that endogenous somatostatin could act as a true hormone; (2) the secretory activity of the somatostatin cell is not significantly affected by circulating gastrin.
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  • 19
    Electronic Resource
    Electronic Resource
    Springer
    Research in experimental medicine 188 (1988), S. 267-276 
    ISSN: 1433-8580
    Keywords: Splenic autotransplantation ; Phenylhydrazine ; Malaria infection ; Rat ; Blood flow
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary After splenic autotransplantation both weight and blood flow of the regenerated splenic tissue are decreased. In addition, the protective function of the transplant is less compared to that of the normal spleen. In the present study, the red pulp of normal and transplanted splenic tissue was stimulated by injections of phenylhydrazine to increase the weight, the blood flow, and the protective function. After stimulation, the weight of the normal spleen increased to 900 ± 70 mg (control 530 ± 20 mg) and the transplanted tissue to 240 ± 70 mg (control 70 ± 20 mg). This enlargement was caused by an increase in the splenic red pulp. However, the relative blood flow decreased in both the normal spleen and the transplant to 50% of the normal value. To evaluate the protective function of the stimulated splenic tissue, normal, splenectomized and transplanted rats were infected withPlasmodium berghei. Despite the dramatic increase in the red pulp, neither the normal nor the transplanted animals showed a survival rate superior to that of the splenectomized animals. The mass of splenic tissue obviously does not correlate with the protective effect of the spleen in parasitic infections.
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  • 20
    ISSN: 1434-0879
    Keywords: Renal transplantation ; Rat ; Ultraviolet irradiation ; PUVA ; Pulsatile perfusion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Systemic photochemical pretreatment of a rat kidney donor with the photosensitizer 8-methoxypsoralen (8-MOP; 0.06 mg/kg intravenously, 10 min before graft removal) plus ex vivo longwave ultraviolet (UVA) irradiation of the kidney graft during simple hypothermic storage significantly prolonged survival time in allogeneic recipients. In contrast to these results, the present use of UVA irradiation during hypothermic pulsatile kidney perfusion using Euro-Collins® solution containing 8-MOP (0.06 mg/ml) did not prolong graft survival compared with untreated controls. Systemic application of 8-MOP to the kidney donor may be necessary for effective action of the combined photochemical treatment as a method of immunoalteration. The extended UVA irradiation time and the local use of 8-MOP in the preservation fluid had no effect on graft survival possibly because of inadequate tissue distribution of 8-MOP during both hypothermia and perfusion.
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  • 21
    Electronic Resource
    Electronic Resource
    Springer
    Urological research 16 (1988), S. 277-280 
    ISSN: 1434-0879
    Keywords: Electrical stimulation ; Stretching ; Time factor ; Bladder strip ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Distension of the human urinary bladder often causes prolonged impairment of its function. To investigate the effects of the duration of stretch on bladder smooth muscle the active length-tension relation, electrically evoked, was described in rat detrusor strips during a short-term and a long-term stretch. The amplitude of active tension increased at first and then decreased abruptly at greater stretch lengths, the maximum being at muscle lengths 230–250% (100%=resting length) in both types of stretches. When the strips had been at maximum length (300%) for three hours the amplitude was significantly decreased during release as compared to the amplitude found during stretch to the maximum length at comparable lengths. If the strips were released immediately from the maximum length the amplitude responded in an opposite manner. Therefore we conclude that the duration of stretching of bladder smooth muscle significantly affects its mechanical activity.
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  • 22
    ISSN: 1433-8580
    Keywords: Rat ; Intestinal ammoniagenesis ; Glutamine metabolism ; Small intestine ; Colon
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The intestinal ammonium production and the intestinal uptake of circulating glutamine were investigated in anesthetized intact rats and rats with resected small intestine or colon by simultaneous measurements performed on portal and arterial blood. It was shown that ammonium release into the portal blood by the small intestine is of equal magnitude to that released by the colon, and that circulating glutamine participates in ammonium production by the small intestine. Increased levels of circulating glutamine induced by its i.v. infusion to intact rats were not accompanied by an increase in intestinal ammonium production.
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  • 23
    Electronic Resource
    Electronic Resource
    Springer
    Research in experimental medicine 188 (1988), S. 123-129 
    ISSN: 1433-8580
    Keywords: Acute experimental pancreatitis ; Sodium taurocholate ; Pancreatic enzymes ; Pancreatic morphology ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Sodium taurocholate pancreatitis in the rat is a frequently used experimental model for evaluating therapeutical regimes in this disease. It is, however, uncertain when treatment should be started, as the early phase of this experimental model and thus the time when the pancreatitis really develops is unknown. Serum and pancreatic enzymes, as well as pancreatic morphology, were therefore studied 5, 30, and 60min after induction of sodium taurocholate pancreatitis. It was found that increase in serum enzymes and decrease in pancreatic enzymes and morphological changes characteristic for acute pancreatitis develop as early as 5 and 30 min after induction of pancreatitis. Thus, therapy in this model may be started shortly after induction of acute pancreatitis.
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  • 24
    Electronic Resource
    Electronic Resource
    Springer
    Anatomy and embryology 177 (1988), S. 349-352 
    ISSN: 1432-0568
    Keywords: Pineal body ; Mongolian gerbil (Meriones unguiculatus) ; Rat ; Calbindin D-28K (vitamin D-dependent calcium binding protein) ; Immunocytochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Immunocytochemical reaction for demonstration of calbindin D-28K has been performed in superficial pineal bodies of the Mongolian gerbil (Meriones unguiculatus) and the rat. Whereas in the Mongolian gerbil there were no clearly expressed calbindin immunoreactive cells, these were numerous in the rat pineal body. Here the calbindin-positive cells — probably pinealocytes — were disposed along capillaries. In view of the role of calbindin in binding and transporting calcium and regulating its intracellular levels, the absence of this protein in the gerbil pineal body has been interpreted as signifying the inability of pinealocytes to eliminate intracellular calcium with possible consequent formation of acervuli.
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  • 25
    ISSN: 1432-0568
    Keywords: Atrial specific granule ; Atrial natriuretic polypeptide ; Impulse conducting system ; Immunohistochemistry ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The present study was performed to clarify the distribution of ANP-containing cells in the adult rat heart by immunostaining for ANP using antiserum against α-human ANP. ANP-immunoreactive cells were generally present in the atrial walls except for the sinoatrial node. In the ventricular walls, they were distributed in the impulse conducting system, particularly the left bundle branch, Purkinje fibers on the left side of the interventricular septum, and those in the false tendons in the left ventricle, while they were sporadically seen in the atrioventricular node and bundle of His. The immunoreactive cells contained specific granules that were positive for ANP. These findings demonstrate that ANP-containing cells are present in the atrial and ventricular walls.
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  • 26
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    Acta neuropathologica 77 (1988), S. 219-223 
    ISSN: 1432-0533
    Keywords: Meningioma ; Folliculo-stellate cell ; Pituitary neoplasm ; Electron microscopy ; Immunochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A tumor arising in the pituitary fossa and having some of the histological and ultrastructural features of a recently described tumor, purportedly originating from the folliculo-stellate cells of the anterior pituitary, is presented. The results of our ultrastructural and immunohistochemical studies, however, favored a meningeal origin and suggested that the neoplasm was most likely a secretory meningioma.
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  • 27
    ISSN: 1432-0533
    Keywords: Blood-brain barrier ; Hyperosmolar solutions ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Infusion of hypertonic solutions into the carotid artery is one method by which the blood-brain barrier (BBB) can be opened transiently in experimental animals. This technique has also been tried in clinical situations in which an enhanced uptake of intravenously injected chemotherapeutic drugs into the brain is desired. We have previously found that infusion of hypertonic mannitol or urea into the carotid artery of the rat, leading to a BBB opening, is associated with light microscopic signs of cellular damage in the brain parenchyma. An electron microscopic study has now been made to obtain more detailed information about the events taking place in the rat brain 1 to 72 h after an intracarotid infusion of hyperosmolar solution of mannitol. Toluidine blue-stained semithin epon sections were also available for high-resolution light microscopy of brain samples from urea-infused animals. Intravenously injected Evan's blue dye was used to confirm that BBB opening had occurred as a consequence of the carotid infusions. The infused hemispheres had numerous structural changes. The dominating light microscopic alteration was the presence of multifocal lesions in the gray or the white matter with closely packed microvacuoles causing status spongiosus. Ultrastructurally the microvacuoles corresponded to very pronounced watery swelling of astrocytic processes and to a minor degree to expansion of dendrites and axons. There was also a light or moderate perivascular astrocytic swelling. In the “spongy” lesions as well as occasionally in non-vacuolated parts of the cerebral cortex, there were collapsed electron-dense neurons with pronounced mitochondrial alterations such as severe swelling associated with rupture of christae. Rats with a survival period of 24 h or 72 h showed several disintegrating neurons and accumulation of macrophages. This study shows that carotid infusion of hypertonic mannitol in the rat may cause pronounced neuronal changes as well as multifocal astrocytic swelling. The severity of the nerve cell changes and the presence of macrophages indicate that some of the alterations are irreversible and thus, such a procedure may not be as safe as previously suggested.
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  • 28
    ISSN: 1432-0533
    Keywords: Stroke-prone spontaneously hypertensive rats ; Blood-brain barrier ; Brain edema ; Nerve cell injury ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The brain lesions in stroke-prone spontaneously hypertensive rats (SHRSP) are characterized by multifocal microvascular and spongy-cystic parenchymal alterations particularly in the gray matter. An essential feature of the lesions is the presence of edema with massive extravasation of plasma constituents as evidenced by specific gravity measurements, Evans blue technique and immunohistochemistry. The nerve cell injury occurring in the brain lesions in SHRSP is further characterized by light and electron microscopy in the present study. Two types of neuronal changes were seen within the blood-brain barrier (BBB) leakage sites. A small number of neurons with dark condensed nucleus and cytoplasm were found most often at the periphery of recent lesions. The majority of injured neurons were pale and showed intracellular edema confined to the dendrites and perikarya sparing axons and synapses. Their nuclei were weli preserved with finely dispersed chromatin. The swollen and watery cell processes of neurons and astrocytes gave a spongy appearance to the neuropil. The intracellular edema seemed to result in cytolysis. The results suggest that primary anoxiaischemia is not the major pathogenetic mechanism behind the nerve cell injury in severely hypertensive SHRSP, rather it is the massive BBB leakage and consequent brain edema that causes cytolytic destruction of neurons. Secondary focal ischemia as a consequence of occlusion in microvessels may, however, contribute to the nerve cell destruction.
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  • 29
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    Acta neuropathologica 76 (1988), S. 253-264 
    ISSN: 1432-0533
    Keywords: Cerebral ischemia ; Rat ; Hyperglycemia ; Postischemic seizures ; Substantia nigra
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary This study explores how hyperglycemia and enhanced tissue lactic acidosis influence the density and distribution of ischemic brain damage. Ischemia of 10-min duration was produced in glucose-infused rats by bilateral carotid clamping combined with hypotension, and the brains were perfusion-fixed with formaldehyde following recirculation of 3, 6, 12 and 18 h. After about 24 h the hyperglycemic animals developed seizures, and at that time two groups were added, one fixed prior to, and one after the onset of seizures. Similar experiments were made on normoglycemic animals with recirculation times of 1.5 to 96 h. After fixation the brains were embedded in paraffin, subserially sectioned and stained with celestine blue/acid fuchsin. In both normo- and hyperglycemic animals, neurons in the dentate hilus of the hippocampal formation and in the thalamic lateral reticular nucleus showed early and dense neuronal necrosis. In neocortex, hippocampal CA1 sector and caudoputamen, hyperglycemia shortened the delay before damage occurred and markedly enhanced the damage. Specific for the hyperglycemic animals was damage of the substantia nigra, pars reticulata (SNPR), manifest already at the earliest recovery periods studied; this finding is discussed in relationship to the role SNPR is assumed to play in preventing spread of seizure discharge.
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  • 30
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    Anatomy and embryology 177 (1988), S. 267-275 
    ISSN: 1432-0568
    Keywords: Septal nuclei ; Prenatal development ; Quantitative histology ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Prenatal development of septal cell groups was studied in the rat on samples taken daily from the 14th day of gestation until birth. Coronal serial sections of brains were prepared in which the topography coordinates of septal nuclei were determined, their section profiles measured and their volumes calculated. The rat septum begins to develop on embryonic days 14–15. First the individual neurons start to differentiate, then cell groups characteristic for the adult are formed between days 14 and 17, which is followed by the delineation of nuclei. The only exception is the anterior subdivision of the lateral septal nucleus where the formation of the nucleus precedes the differentiation of its constituent cells. The individual nuclei start to develop at different times defined by a medio-lateral gradient of cell migration. By embryonic day 20 the formation of the nuclei can be considered as complete: all septal nuclei and their subdivisions are to be recognized and distinguished from each other.
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  • 31
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    Anatomy and embryology 177 (1988), S. 325-330 
    ISSN: 1432-0568
    Keywords: Isthmic nucleus ; Electron microscopy ; Tectal ablation ; Xenopus ; Morphometry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The isthmic nucleus (IN) of the frog brain forms a linkage, relaying visual information from one tectum to the other. It receives afferent input from the tectum of the same side and projects bilaterally to both tecta. The ultrastructural features of the tecto-isthmic synaptic connections were studied in young postmetamorphic Xenopus frogs. Most synaptic profiles in the isthmic nucleus have spheroidal vesicles and an asymmetric zone of apposition. Frequently, synaptic glomeruli consisting of up to 8 terminal boutons surrounding a shaft dendrite were observed. The syanptic density in the rostral IN was slightly higher than in the middle or caudal portions. Partial deafferentation by transection of the tectoisthmic pathway or total deafferentation by removal of the tectum was followed by a widespread degeneration of terminals in the ipsilateral IN. In the former case, the density of synapses in the IN decreased initially by about 64%, and then increased by 30 days after operation to about 50% of the normal synaptic density. After tectal removal, all the terminal boutons in the isthmic neuropil degenerated by 3 days after operation. These studies, along with recent findings, indicate that most, if not all, of the afferent fibres to IN are of tectal origin.
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  • 32
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    Anatomy and embryology 177 (1988), S. 485-493 
    ISSN: 1432-0568
    Keywords: Ventral tegmental nucleus of Gudden ; Dorsal tegmental nucleus of Gudden ; Quantitative morphometric study ; Synaptic organization ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The fine structure of neuronal somata and axosomatic synapses in each subnucleus of Gudden's tegmental nuclei was studied by use of electron microscopy. The pars principalis of the ventral tegmental nucleus of Gudden (TVP) is composed of oblong or triangular, medium sized neurons (11.8x22.6 μm, 211.4 μm2) containing many mitochondria, lysosomes, Golgi apparatus, and rough endoplasmic reticulum composing Nissl bodies. The light oval nucleus with a prominent nucleolus is centrally situated, and indentations of its nuclear envelope are recognized in all neurons. The neuron in the pars ventralis of the dorsal tegmental nucleus of Gudden (TDV) is similar to that in the TVP, but its average size is significantly smaller (10.0x18.8 μm, 151.4 μm2), and its organelles are also less well developed. The pars dorsalis of the dorsal tegmental nucleus of Gudden (TDD) is composed of spindle shaped, small neurons (6.9x16.2 μm, 85.1 μm2) characterized by their irregular shaped nucleus with its invaginated envelope. These neurons have a thin rim of cytoplasm, poorly developed organelles and no Nissl bodies. The average number of axosomatic terminals in a sectional plane is 9.9 in the TVP, 9.6 in the TDV and 2.6 in the TDD, and the bouton covering ratio is 24.3% in the TVP, 26.5% in the TDV and 7.4% in the TDD. The respective percentages of round, flat and pleomorphic type axosomatic terminals were estimated, and the flat type terminals were found to be dominant in the TVP, the pleomorphic type terminals in the TDV, and the round type terminals in the TDD.
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  • 33
    ISSN: 1432-0568
    Keywords: Primary afferents ; Muscle ; Anterograde tracing ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The sternomastoid muscle of the rat is divided into a white (dominated by fast-glycolytic twitch fibers) and a red (dominated by fast oxidative-glycolytic twitch fibers, but also containing slow-oxidative twitch fibers) compartent. Previous reports on exclusive location of muscle spindles in the red portion were confirmed. On the basis of anterograde labeling with horseradish peroxidase-wheat germ agglutinine conjugate (WGA-HRP) it was shown in this study that, in addition to muscle spindle compartmentalisation, there was also an exclusive occurrence of tendon organs in the red part of the muscle; moreover, fine afferents (III- and IV-afferents) were mainly distributed to this portion as well. Radioimmunassay studies revealed that this part of the muscle contained twice as much substance P as the white part. It could be shown by acetylcholinesterase (AChE) histochemistry that the myelinated fibers of the white branch to the muscle exclusively displayed high enzyme activity which is characteristic for motor fibers; on the other hand, in the branch to the red portion two classes of AChE-positive fibers were found: a large one with a peak in the alpha-range, and a small one with a peak in the gammarange. In addition, there was also a group of enzyme-negative (sensory) fibers. These results also indicate the red portion of the sternomastoid muscle to be its “sensory compartment”.
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  • 34
    ISSN: 1432-0568
    Keywords: Electron microscopy ; Glial cells ; Perivascular cells ; Lipid droplets ; Wallerian degeneration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Kittens were subjected to lumbosacral dorsal rhizotomies at the age of 6–8 days postnatally. After postoperative survival times of 1–25 days the number of non-neuronal cells and lipid droplets in each cell type in the posterior funiculus at L1 were counted at the ultrastructural level. Intact control animals were analyzed in the same way. The number of astrocytes and oligodendrocytes decreased with increasing postoperative survival time in the degenerating zone. This was also the case in the white matter of control animals with increasing age of sacrifice. However, in the degenerating zone of operated animals the decrease was more extensive for oligodendrocytes starting at 5 days after surgery, and possibly also for astrocytes at 25 days postoperatively. The number of microglial cells in the degenerating zone was markedly increased 2–10 days after surgery compared to the controls. The number of non-pericytic perivascular cells seemed to be somewhat increased from 9 days after surgery, while the number of pericytes remained unchanged during the experimental period. Lipid droplets in the degenerating white matter were mainly located in microglial cells and astrocytes and only to a small extent in nonpericytic perivascular cells. These findings suggest that lipid material produced during anterograde fiber degeneration in the immature white matter is mainly metabolized in glial cells.
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  • 35
    ISSN: 1432-0568
    Keywords: LHRH ; Rat ; Maturation ; Sex-difference
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Luteinizing hormone-releasing hormone (LHRH) neurons were immunohistochemically studied in rats of both sexes at peripubertal ages. The number of immunoreactive LHRH neurons (irLHRH neurons) was counted in the brain region from the level of the septumpreoptic area to the level of the rostral part of the infundibulum in colchicine-treated male and female rats at 30 and 60 days of age. At 30 days, irLHRH neurons were more numerous in male rats than females. At 60 days, the number of irLHRH neurons in female rats increased to the level of male rats of the same age. In non-colchicine-treated rats, the count of irLHRH neuron was quite low. The difference in the number of irLHRH neurons between colchicine-treated and non-treated rats may be regarded as the activity of LHRH system. The difference in the number of irLHRH neurons was larger in male rats than in female rats at 30 days of age. On the contrary, at 60 days of age, the difference was larger in females than in males. LHRH contents were measured in the preoptic-anterior hypothalamic area (POA-AH), where LHRH neuronal perikarya are mainly located, and in the mid-hypothalamic area. LHRH content of the POA-AH in male rats at 60 days of age was not significantly different from that at 30 days of age. While, LHRH content in the POA-AH was greater in 60-day-old female rats at proestrous morning than that in 30-day-old females. At 30 days of age, male rats tended to contain more LHRH in the POA-AH than female rats. However, either at 30 days or at 60 days, no statistically significant differences were detected between male and female rats. In mid-hypothalamic area, LHRH content in 60-day-old male rats was greater than that in 30-day-old male rats. On the other hand, there was no difference in LHRH content between 30-day-old and 60-day-old female rats. At 60 days of age, LHRH content in male rats was greater than that in female rats. The present morphological findings and LHRH measurements suggest that the functional maturation of LHRH system occurred earlier in male rats than in female rats.
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  • 36
    ISSN: 1432-0568
    Keywords: Pancreatic islet ; Insulin ; Glucagon ; Ontogeny ; Immunohistochemistry ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Ontogenetic appearances of glucagon, insulin and tyrosine hydroxylase (TH) were immunohistochemically investigated on developing pancreatic islets of rats. Glucagon immunoreactivity appeared first in some epithelial cells (g-cells) of the dorsal anlage of the pancreas on day 11.5 of gestation. On day 12.5, g-cells increased in number manufacturing the primitive islets, in which some cells appeared to be immunoreactive for insulin (i-cells) and about 40% of g-cells indicated also a slight immunoreactivity for insulin (g/i-cells). Afterwards, all the islet cells, especially g-cells, increased in number, and almost half of g-cells were g/i-cells. After day 16.5 of gestation, numerical increase of the cells with insulin immunoreactivity exceeded that of the cells with glucagon immunoreactivity, and about one fifth of g-cells were g/i-cells. After 20.5 days, however, no g/i cells were found. On day 16.5 of gestation, the immunoreactivity for TH appeared in occasional cells of the islets, but the cells did not show immunoreactivity for glucagon or insulin. It is concluded that the progenitor cells of the pancreatic islets appear to synthesize both glucagon and insulin by day 20.5 of gestation, but differentiate giving rise to mature A and B cells of adult isoets afterward.
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  • 37
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    Anatomy and embryology 178 (1988), S. 175-181 
    ISSN: 1432-0568
    Keywords: Liver development ; Adrenergic innervation ; Enzymic zonation ; Rat ; Spiny mouse
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The development of noradrenergic innervation of rat liver was studied with a polyclonal antiserum against noradrenaline. Nerves are first seen in the larger portal vessels at day 1 after birth and reach their final distribution at 5 days after birth i.e. at the same time as the establishment of the acinar architecture and the heterogeneous distribution of NH3-metabolizing enzymes. The latter distribution of nerves is already seen at birth in the liver of the closely related but precocial spiny mouse. This shows that the onset of extrinsic sympathetic innervation is regulated by the developmental stage of the animal rather than by adaptation to extrauterine life. Chemical sympathectomy at birth with 6-hydroxydopamine did not eliminate the developmental appearance of heterogeneous distributions of NH3-metabolizing enzymes.
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  • 38
    ISSN: 1432-0568
    Keywords: Visual cortex ; VIP ; Neuronal types ; Axonal branching ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Vasoactive intestinal polypeptide (VIP)-immunoreactive cells in the primary visual cortex of the rat were classified on the basis of ramification pattern of cell processes. The distribution of cells over cortical layers, and proportions of cell classes relative to total cell numbers were evaluated by means of quantitative methods. Two main types of VIP-positive neurons, the bipolar and the multipolar were distinguished constituting 76% and 24% of the VIP populations, respectively. The axons of vertically oriented bipolars were observed to ramify within a column around the descending dendrite. By contrast, multipolar cells have a non-oriented ramification pattern. The two overlapping axonal systems form the VIP-innervation of the rat visual cortex.
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  • 39
    ISSN: 1432-0568
    Keywords: Visual cortex ; VIP ; Synapse ; Spatial distribution ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In the rat visual cortex vasoactive intestinal polypeptide (VIP)-containing structures were studied by means of light and electron microscopy and image analysis. VIP-immunoreactive axon terminals were found to form symmetric synapses with small dendritic shafts, dendritic spines and somata of pyramidal cells and interneurons. VIP-terminals often occured in pairs with VIP-negative, asymmetric synapses on the same postsynaptic structure. VIP-immunostained dendrites and perikarya were contacted by a purely asymmetric and a mixed population of VIP-negative terminals, respectively. Synaptic connections between two VIP-neurons are seldom as compared to the other types of VIP-synapses. Quantitative studies obtained by the image analysis of VIP-stained boutons and dendritic particles in light microscopic preparations suggest a distinct laminar distribution. Dendritic particles are most frequent in layers I–II, whereas axonal boutons have three laminar accumulations: at the border of layers I–II, in layer IV and layer VI. Together with previous results, the present findings argue for a non-random spatial distribution of VIP-boutons.
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  • 40
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    Anatomy and embryology 178 (1988), S. 229-241 
    ISSN: 1432-0568
    Keywords: Room temperature ; Visible light ; Preimplantation embryos ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Early cleavage stage embryos (day 1 p.c.) and morulae (day 3 p.c.) of rabbits were exposed to visible (standard) lighting (1600 lx) and room (standard) temperature (23°C) during a 24 h in-vitro culture. Control embryos were cultured in darkness at 37°C. Development was assessed by light and electron microscopy as well as by the cytochemical demonstration of glycogen. In day 1 and day 3 embryos standard temperature induced swelling of the SER and Golgi complex vesicles. Major changes in day 1 embryos consisted of smallish microtubules-like crystalloids, and in day 3 embryos of unusually large SER vesicles. In both embryonic ages cleavage rate and development was more retarded by standard temperature than by standard lighting. Standard lighting, however, led to distinct signs of degeneration and cell death. The mode of cell damage seemed to be different in light exposed early cleavage stages and morulae: In day 1 embryos cytoplasmic degeneration was predominant while the majority of cells in day 3 embryos died by apoptosis. Despite clear indications of cell damage, cleavage rate was not notably impaired compared with non-exposed controls. Glycogen increased during development from cleavage stages to early blastocysts. The distribution was not changed either by exposure to standard temperature nor by standard lighting. The results demonstrate that day 1 embryos were clearly more susceptible to lighting whereas day 3 embryos were more affected by temperature. The mode of damage exerted by both the physical environmental factors was different. Reduction to standard temperature interfered mainly with the organization of the cytoskeleton and intracellular transport of organelles, while exposure to standard lighting led to cell degeneration and death.
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  • 41
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    Anatomy and embryology 178 (1988), S. 309-326 
    ISSN: 1432-0568
    Keywords: Axons ; Cilia ; Microvilli ; Olfactory ; Respiratory ; Development ; Freeze-fracturing ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Olfactory axons and apical structures of olfactory epithelia and of nasal respiratory epithelia of rat embryos were studied with the freeze-fracture technique; adult tissue samples of the same sources were used for comparison. At the onset of epithelial differentiation (14th gestational day) intramembranous particle densities are the same for all structures in both epithelial types. During further development, particle densities in membranes of primary cilia remain lower than those in membranes of other apical structures. Otherwise, I found the following from the 14th to the 19th day of gestation.a. Olfactory receptor cells of embryos of all age groups have axons wherein the membrane particle densities are about half those of adults. These densities are always lower than those of dendritic ending structures. Dendritic endings with primary cilia have lower densities than endings with secondary cilia; densities mainly increase when the endings sprout secondary cilia. Adult values are reached at the 18th day of gestation.b. Olfactory supporting cells with only globular particles in their apices gradually transform into, or are replaced by, supporting cells which also have dumbbell-shaped particles in their apices. Particle densities are always higher in apical structures of supporting cells than in apical structures of receptor cells. Adult values are reached at the 17th day of gestation.c. Putative ciliated and ciliated respiratory epithelial cells have considerably lower particle densities in membranes of their apical structures than do olfactory epithelial cells. Of special interest is that this is also true for secondary respiratory and olfactory cilia; as soon as genesis of secondary cilia in either epithelial type begins, their membrane features differ. Also, in contrast to apical structures of the olfactory epithelium, particle densities in apical structures of the respiratory epithelium do not systematically change during pre-natal development, and resemble the density values of adults. An exception are the microvilli of the respiratory cells with secondary cilia, membranes of which have considerably higher particle densities in adults than in embryos. In conclusion: Transformations of olfactory receptor cell dendritic endings with primary cilia into endings with secondary cilia, and of olfactory supporting cells with globular particles in their apices into cells with dumbbell-shaped particles in their apices are accompanied by increases in the densities of their intramembranous particles. These developmental changes parallel the electrophysiological onset of olfactory receptor cell specificity.
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  • 42
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    Anatomy and embryology 179 (1988), S. 89-96 
    ISSN: 1432-0568
    Keywords: Tendon ; Myotendinous junction ; Fibroblast ; Muscle overloading ; Hypertrophy ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Overloading of rat plantaris muscles was produced by aseptic ablation of the synergists. The morphological changes occurring after 1 or 2 weeks were investigated at the light and electron microscopical level in the distal tendon of the plantaris and at the myotendinous junction. Sham-operated rats were prepared as controls. In the tendon, quiescent fibrocytes were replaced by activated fibroblasts displaying a vesicular nucleus with prominent nucleoli and an outstanding increase in cytomembranes, particularly the rough endoplasmic reticulum and the Golgi complex. The plasmalemma of the fibroblasts was modified by the presence of caveolae and the surbsurface cytoplasm contained many membrane-bound vacuoles. In the tendon, the collagen bundles were disrupted, resulting in the formation of empty longitudinally oriented spaces; in these spaces, as in the pericapillary areas, no inflammatory cells were observed. At the myotendinous junction, fibroblast activation was consistently observed in both control and overloaded specimens. At this level, the sarcolemma of the finger-like projections of muscle fibres presented many caveolae close to clusters of large subsurface vacuoles. These observations indicate that, at the beginning of the compensatory hypertrophy, the adaptative changes to overloading include a non-inflammatory reaction of the tendon characterized by enhanced collagen synthesis and intensive membrane renewal and recycling. From the mechanical point of view this reaction can impair the tendon resistance to stretch. At the myotendinous junction the increased membrane turnover of the sarcolemma and the fibroblast activation can be considered permanent phenomena consequent to the increased stress exerted upon the interface connecting the contractile apparatus to the stroma.
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  • 43
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    Anatomy and embryology 179 (1988), S. 109-127 
    ISSN: 1432-0568
    Keywords: Rat ; Inferior olive ; GABA ; Glutamate decarboxylase ; Cerebellar circuitry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Boutons presumed to use γ-aminobutyric acid as neurotransmitter (GABAergic boutons) were detected by glutamate decarboxylase (GAD) immunocytochemistry in all regions of the rat inferior olive. The remarkably high concentration of these boutons allowed a clear visualization of olivary subnuclei boundaries. Regional variations in GAD immunostaining intensity were observed within the nuclear complex and were graded both visually and photometrically. The regional staining variations, for the most part, followed subnuclei boundaries and olivary zonal compartments that have been delineated by the topography of climbing fiber projections. Some subnuclei were grouped by similar staining intensities. The beta nucleus and a medial region in the ventral fold of the dorsal accessory olive were most intensely immunostained, followed by the subnucleus c of the medial accessory olive. Lower staining intensities were observed in the dorsomedial cell column, the dorsal fold of the dorsal accessory olive and the dorsal cap. The lowest intensities were observed in the subnuclei a and b of the medial accessory olive, the ventrolateral outgrowth, the rostral lamella of the medial accessory olive, the principal olive, and the lateral part of the ventral fold of the dorsal accessory olive. The factors contributing to the variations in immunostaining intensity (bouton size and frequency of occurrence) were investigated. The largest boutons were observed in the beta nucleus. Intermediate sized boutons were observed in the dorsomedial cell column, dorsal cap and the dorsal fold of the dorsal accessory olive. The smallest boutons were present in the remaining regions of the inferior olive, including the principal olive, the rostral lamella of the medial accessory olive, and the ventral fold of the dorsal accessory olive. The medial region of the dorsal accessory olive ventral fold contained a higher density of GABAergic boutons than other regions. GABAergic bouton size and innervation density therefore largely accounted for the variations in GAD immunostaining intensity. This study provides a map of the rat inferior olive based on the distribution of GABAergic nerve terminals, and may serve as a basis for characterizing different GABAergic afferent systems in the inferior olive.
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  • 44
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    Anatomy and embryology 178 (1988), S. 297-307 
    ISSN: 1432-0568
    Keywords: Rabbits ; Islands of Langerhans ; Electron microscopy ; Immunohistochemistry ; Regulation of islands
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In addition to “external” signals conveyed by the circulation or the nervous system, the pancreatic islets obviously are regulated also by “internal” (intra-islet) signals, e.g. by the islet hormones: insulin (B-), glucagon (A-), and somatostatin (D-) cells are able to affect the secretion of the heterologous cell types. It is, however, unclear whether this functional cooperation between islet cells occurs by an intercellular route (paracrinia sensu strictore), by intraislet “portal” vessels, or by the systemic circulation. These likely interactions are limited by islet anatomy. To identify the anatomical basis for the mutual functional relationships between the islet cells, islets of Langerhans in the rabbit pancreas were completely analyzed in immunostained serial semithin (0.5 μm) sections. The islets were found to be largely heterogenous. They were classified in three basic types: a) polycellular islets, composed of all established endocrine cells, and including two subtypes of islets, b) bicellular islets, containing only B- and A-cells or B- and D-cells, and c) monocellular islets, exclusively made up of B-cells. Concerning the modes of paracrine regulation of islet cells, the findings suggest primarely an endocrinous route of transport of the islet peptides to heterologous endocrine cells. The corresponding functional cooperation between islet cells probably is mediated rather by the systemic circulation than by intra-islet portal vessels.
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  • 45
    ISSN: 1432-0568
    Keywords: Cadmium, Placenta (rat) ; Morphometry ; Light microscopy ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The morphology of the rat placenta was studied after exposure to cadmium chloride during pregnancy, using optimal fixation conditions. In contrast to previous observations, no differences were observed after cadmium administration in relative volume densities of trophoblastic tissue, maternal lacunae, fetal capillaries and connective tissue, nor in trophoblastic thickness or other morphometric features. At the ultrastructural level, the amount of glycogen in trophoblast layer II was elevated in cadmium exposed rats, but other electron microscopic features (amount and localization of lipid, degenerative vesicles, thickness and general appearance of the trophoblastic and endothelial layers and thickening or multiplication of the basal lamina) were not changed. Results obtained from the present experiments do not support the suggestion that cadmium is responsible for structural changes in the placentae of human smokers.
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  • 46
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    Anatomy and embryology 178 (1988), S. 119-127 
    ISSN: 1432-0568
    Keywords: Neuronal differentiation ; Fascia dentata ; Granule cells ; GABAergic neurons ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Golgi impregnation was used to study the dendritic differentiation of granule cells in the rat fascia dentata. The impregnated granule cells were gold-toned allowing for a fine structural study of the same identified neurons and of the input synapses onto their cell bodies and dendrites. Due to the long postnatal formation of these cells it was possible to describe a sequence of maturational stages coexisting on the same postnatal day (P5). Characteristic features of the dendritic development of granule cells were i) occurrence of varicose swellings along the dendrites, ii) growth cones on dendritic tips, iii) transient formation of basal dendrites, and iv) progressive development of dendritic spines. Incoming synapses on the differentiating granule cells were mainly found on dendritic shafts. Their membrane specializations were symmetric. At least some of these symmetric synapses were GABAergic because immunostaining of Vibratome sections from the same postnatal stage (P5) demonstrated a well-developed GABAergic axon plexus in the fascia dentata (antibodies against glutamate decarboxylase (GAD), the GABA synthesizing enzyme). Electron microscopy of the immunostained axon plexus revealed numerous GABAergic terminals that formed symmetric synaptic contacts, mainly on shafts of differentiating dendrites but also on cell bodies of granule cells. Our results thus indicate that the plexus of inhibitory GABAergic axons is already well developed at a stage when the target neurons, the granule cells, are still being formed.
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  • 47
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    Anatomy and embryology 178 (1988), S. 155-159 
    ISSN: 1432-0568
    Keywords: Interhemispheric pathway ; Congenital anophthalmia ; Visual cortex ; Development ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In an effort to assess the innate capacity of the central visual system to specify corticocortical connectivity in the absence of retinal afferents, we examined the tangential distribution of callosal cells and terminations in posterior neocortex of congenitally anophthalmic rats. Although our results indicate that the callosal pattern is clearly anomalous in these rats, all features of the normal visual callosal pattern are recognizable in mutant rats, indicating that central visual pathways can generate many aspects of normal interhemispheric connectivity in the absence of input from the periphery. On the other hand, the presence of anomalies in the pattern indicates that the eyes are necessary to finetune the distribution of callosal connections at some developemental stage. Moreover, the fact that abnormalities in the callosal pattern of mutant rats are the same as those previusly described in rats enucleated at birth suggests that the eyes begin to exert their influence on callosal development after birth.
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  • 48
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    Anatomy and embryology 178 (1988), S. 381-388 
    ISSN: 1432-0568
    Keywords: Ciliary necklaces ; Olfactory ; Vomeronasal ; Respiratory ; Development ; Freeze-fracturing ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Many cilium types have at their proximal base a particulated membrane structure, the so-called ciliary necklace. Necklaces of primary and secondary cilia of olfactory receptor cells and ciliated respiratory cells, and of primary cilia of olfactory supporting cells were studied as a function of embryonic age. Strand numbers in necklaces of primary cilia of these cell types do not differ, but they differ significantly from those of necklaces of secondary cilia. Primary cilia have 2 to 4, but most commonly 3, necklace strands. This is true for necklaces of primary cilia of 8 different nasal cell types: olfactory epithelial basal and glandular cells, vomeronasal receptor and supporting cells, and microvillous respiratory epithelial cells, in addition to the 3 cell types mentioned above. Comparison with other systems suggests that primary cilia resemble flagella of eukaryotic flagellates and spermatozoa of some invertebrates with respect to their number of necklace strands. Average numbers of necklace strands in secondary olfactory cilia increase from 3–4 at the 16th and 17th gestational days to 6–7 in adults. Those in secondary respiratory cilia increase from 2–3 at the 18th and 19th gestational days to 5–6 in adults. Longer cilia have more strands than shorter ones. Necklaces often have free strand endings, also in primary cilia, suggesting that they spiral. Comparing the present data with those in the literature suggests that necklace features occurring during reciliation differ from those of de novo ciliogenesis. Primary and secondary cilia share the following qualities: 1) Membrane regions above necklace strands can differ quite drastically from those below the strands. 2) Necklace particles are firmly associated with cytoskeletal elements underneath the ciliary membrane. Hence, necklaces in primary cilia and in developing and mature secondary cilia may, together with the cytoskeleton underneath the membrane, provide a barrier for lateral diffusion and a region of membrane attachment. The latter may help to determine the shape of cilia.
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  • 49
    ISSN: 1432-0568
    Keywords: Taurine ; Immunocytochemistry ; Quantification ; Electron microscopy ; Cerebellum ; Purkinje cells
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Ultrathin sections of plastic-embedded rat cerebella were incubated with an antiserum against conjugated taurine and subsequently treated with a secondary antibody coupled to colloidal gold. The density of gold particles in various cellular profiles was calculated with the assistance of a computer. In the cerebellar cortex the highest density was found in the somata, dendrites, and dendritic spines of the Purkinje cells, supporting parallel light-microscopical observations in postembedding stained semithin sections from the same tissue blocks. The remaining profiles could be divided into three groups according to their immunolabelling intensity, in descending order: 1) somata and processes of granule and Golgi cells; 2) somata and processes of stellate, basket, and glial cells, and 3) mossy fiber terminals. In a representative experiment, the structures in the first and second groups showed gold particle densities in the range of 19–25%, and 4–11%, respectively, of that in the Purkinje cell somata (values corrected for background) whereas the particle density in the mossy fiber terminals was not significantly above background level. In the cerebellar nuclei, taurine-like immunoreactivity was concentrated in terminals that typically established symmetric or intermediate type contacts with weakly labelled dendrites and cell bodies. These terminals, which shared the ultrastructural features of Purkinje cell terminals, showed an average gold particle density that was about 60% higher than that of the Purkinje somata. For specificity control, ultrathin sections containing a series of different amino acid conjugates were incubated in the same drops of sera as the tissue sections. The highly selective labelling of the taurine conjugate indicated that the distribution of gold particles in the tissue was not confounded by crossreactivity with GABA, glutamate or other common amino acids but adequately reflected the distribution of fixed taurine. For additional control of specificity, the taurine antiserum was applied to the soluble fraction of a rat brain extract separated by thin layer chromatography. In this system the taurine antiserum stained a single spot that comigrated with free taurine. The present results suggest that all cell types and processes in the rat cerebellum (with the exception of the mossy fiber terminals) contain taurine. However, the concentration of taurine appears to vary considerably among the different cell types and may also differ between different parts of the same neuron.
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  • 50
    ISSN: 1432-0568
    Keywords: Immunohistochemistry ; Choline acetyltransferase ; Olfactory bulb ; Modified glomerular complex ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The main and accessory olfactory bulbs (MOB and AOB) of the rat were immunohistochemically stained with a monoclonal antibody against choline acetyltransferase (ChAT) in order to know the difference in the distribution patterns of cholinergic fibers between these two structures. A few ChAT-immunoreactive cell bodies were found in the superficial and middle parts of the external plexiform layer (EPL) of the MOB, in the granule cell layer (GCL) of the MOB, and in the GCL of the AOB. The frequency in appearance of these cells was 0.9 cells/section in the MOB and 0.3 cells/section in the AOB. While the glomerular layer (GL) and the superficial part of the EPL were most densely innervated in the MOB, the internal plexiform layer received the richest innervation in the AOB. There were no immunoreactive structures in the olfactory nerve layer of the MOB and in the vomeronasal nerve layer and glomerular layer of the AOB. In addition to a relatively homogenous distribution of cholinergic fibers in the MOB and AOB, there were several foci of very dense network of immunoreactive fibers at the posterior level of the OB. These foci formed a part of the modified glomerular complex that was recently identified using 2-deoxyglucose method and was presumed to be related to suckling behaviour in the neonatal rat.
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  • 51
    ISSN: 1432-0568
    Keywords: Rat ; Development ; Diencephalon ; Neuromeres ; Sulcus limitans
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The morphogenesis of the ventricular surface of the diencephalon of the rat was studied using scanning electron microscopy, cryostat serial sections and direct observations under a dissection microscope. Based on these observations a description is given of the neuromeres present within the prosencephalon and of the termination of the sulcus limitans. Two conclusions are reached. First, three neuromeres are present in the prosencephalon. Neuromere I consists of the telencephalon, the hypothalamic regions and the parencephalon anterius. Neuromere II is the parencephalon posterius, neuromere III the synencephalon. Second, the sulcus limitans terminates ventrally in the parencephalon posterius and does not continue towards the preoptic recess. No exact termination point of the sulcus limitans could be delineated.
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  • 52
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    Acta neuropathologica 76 (1988), S. 624-627 
    ISSN: 1432-0533
    Keywords: X-Irradiation ; Intraspinal Schwann cell ; Myelin ; Autoradiography ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A stable population of intraspinal Schwann cells, which developed follwing early postnatal irradiation of the spinal cord, was challenged by the addition of tellurium (Te) to the diet beginning at 30 days of age. Schwann cells incorporating [3H]thymidine were identified by 1 μm autoradiographs and by conventional electron microscopy of adjacent thin sections. Autoradiographs of areas with Schwann cell myclination showed extensive labelling of cells in the Te-fed animals. In contrast, control animals which were not fed Te showed little evidence of labelled Schwann cells. These data indicate that Schwann cells in the intraspinal environment show a proliferative response to the presence of Te in the rat's diet, as do Schwann cells in their normal extraspinal milieu.
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  • 53
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    Acta neuropathologica 76 (1988), S. 638-639 
    ISSN: 1432-0533
    Keywords: Meningioma ; Electron microscopy ; Collagen ; Amianthoid fibers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Electron microscopic examination of a spinal meningioma demonstrated broad zones with large amianthoid collagen fibers in the tumor. Normal native collagen fibrils were found in small scattered clumps particularly around the blood vessels in the tumor. Such abnormal large collagen fibrils have not been seen previously in meningiomas. The significance of the amianthoid fibers is unknown. The only other unusual feature of the tumor was that it had many pale-staining cells by light microscopy and was classified as a clear cell variant of meningioma.
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  • 54
    ISSN: 1432-0533
    Keywords: Chloroquine ; Peripheral neuropathy ; Nerve biopsy ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Nerve biopsies were performed in four patients with suspected chloroquine induced neuromyopathy. Three of the patients were treated with high doses of chloroquine for connective tissue disease, while one patient was taking this drug as malaria prophylaxis. Morphological studies demonstrated the presence of segmental demyelination and remyelination in all cases. Cytoplasmic inclusions were observed in Schwann cells, in perineurial and endothelial cells, and in some interstitial cells. They were never observed within axons. Occasional curvilinear profiles were seen in perineurial and Schwann cells. Perineurial calcifications were observed in two cases. The results of this morphological study suggest that chloroquine neuropathy is essentially due primary involvement of Schwann cells.
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  • 55
    ISSN: 1432-0533
    Keywords: HIV-related relapsing polyneuropathy ; Intrathecal HIV antibodies ; Nerve biopsy ; Electron microscopy ; Schwann cell morphology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary This is obviously the first report on a case with a spontaneous sensu strictu relapsing variant of human immunodeficiency virus (HIV)-related polyneuropathy. Its manifestation preceded LAS. Intrathecal HIV-antibodies developed between the most severe third and fourth episode. Analysis of sural nerve biopsy was consistent with a multifocally accentuated chronic inflammatory demyelination, characterized by unusual onion bulb-like Schwann cell formations with irregular voluminous layers, electron density, aggregation of filaments, multiple indented nuclei, and numerous enclosed collagen pockets. A direct or immune-mediated indirect specific influence on Schwann cell morphology by HIV might be discussed. Virus-like particles and ultrastructural markers of HIV were not detectable.
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  • 56
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    Acta neuropathologica 75 (1988), S. 402-410 
    ISSN: 1432-0533
    Keywords: Spinal cord tumor ; Dog ; Electron microscopy ; Immunocytochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We have studied an unusual, spontaneous, intradural extramedullary spinal cord tumor in 12 dogs. Animals presented with paraparesis and ataxia early in life (11/12 ranged from 6 to 38 months of age) suggesting that these tumors may be congenital. Various breeds of dogs were represented with four cases in German Shepherds and three in retrievers; there was no sex predisposition. Post-mortem examinations revealed a single intradural mass consistently located between T10 and L2, which produced extensive compression of the spinal cord. Metastasis was never observed and significant pathological changes in other organs were lacking. Microscopic examination revealed solid sheets of ovoid to fusiform cells interspersed with areas of acinar and tubular differentiation. Some areas were rarified and focal squamous metaplasia was observed. Ultrastructural features included the presence of a continuous basal lamina, junctional complexes, microvilli and occasional cilia at the apices of acinar complexes. Immunocytochemical studies did not support a neurectodermal origin. At least 13 case reports of this entity have been previously published and have been designated ependymomas, medulloepitheliomas and neuroepitheliomas. A recent case was diagnosed as a nephroblastoma and we feel that this is an interesting and provocative diagnosis. These tumors could result from remnants of renal primordium which becomes trapped between the dura and the developing spinal cord. However, firm evidence of such a histogenesis is not yet at hand.
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  • 57
    ISSN: 1432-0533
    Keywords: Alzheimer's disease ; Neurofibrillary tangle ; Paired helical filament (PHF) ; Electron microscopy ; Computerized digital processing
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The ultrastructure of neurofibrillary tangles of Zlzheimer's disease was analyzed by computerized digital processing of electron micrographs. Processing of the electron micrographs consists of four steps: digitizing the electron micrograph, Fourier transformation, noise filtering and inverse Fourier transformation and Laplacian operation. In the present study, we have confirmed that neurofibrillary tangles are composed of a pair of helical filaments (PHF), which appear characteristically as an unbranched rigid structure. The periodicity of PHF is 78nm on the diffractogram. The dimensions of PHF obtained by our analysis, although basically similar to those described earlier by other investigators using conventional techniques, more precisely defines its structural conformation. We have also demonstrated that the spatial relationship of two filaments appears symmetrical after two-way tilting of the specimen about the axis of rotation. Our observations emphasize the importance of digital image processing as an effective tool for structural analytical research in biology and medicine.
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  • 58
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    Acta neuropathologica 76 (1988), S. 489-495 
    ISSN: 1432-0533
    Keywords: Dermal nerves ; Electron microscopy ; Lysosomal diseases ; Terminal axons
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Skin tissue specimens, obtained from 60 patients afflicted with a diverse range of lysosomal disorders revealed two groups of lesions within dermal axons, largely unmyelinated ones, particularly within axonal terminals: (1) non-specific mitochondria and dense bodies often enlarging the axonal terminal; and (2) disease-specific lysosomal residual bodies, the latter less frequent depending on the incidence and type of lysosomal disorders, i.e., largely only seen in GM2-gangliosidosis due to hexosaminidase A deficiency and mucolipidosis IV, while the spectrum of lysosomal residual bodies in Schwann cells appeared more variegated, especially due to the occurrence of vacuolar lysosomal residual bodies which were never seen within axons. The most frequent location of abnormal intraaxonal constituents in terminal axons indicates a functionally and morphologically impaired retrograde axonal transport but provides no further evidence as to whether the respective parent nerve cell body has also accumulated lysosomal residual bodies. When studying biopsied skin specimens for diagnosis, axonal terminals beneath the epidermis, about sweat glands, and among smooth muscle cells, ought to be incorporated into a comprehensive electron microscopic examination.
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  • 59
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    Experimental brain research 70 (1988), S. 561-568 
    ISSN: 1432-1106
    Keywords: Rhythmic movement ; Licking ; Motor learning ; Hypoglossal activity ; Videorecording ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Rats trained to alternate between two adjacent drinking spouts (each spout is retracted after a single lick and presented again after the animal has licked at the other spout) emit 2.5 licks instead of the optimum 1 lick per spout presentation. The question whether the pacemaker of licking is reset or continues to run during transition between spouts was addressed in three experiments performed in 10 highly overtrained rats. Videorecording analysis of oro-facial activities showed that the rat's mouth was firmly closed during the 500 ms transition between spouts. EEG was recorded from the region of hypoglossal nucleus with implanted bipolar electrodes during continued licking at one spout and during spout alternation. Averaging (n = 256, 1024 ms) centered around the onset of the first lick at the newly contacted spout showed 2–3 lick related potentials in the post-transitional interval whereas only one such wave occasionally appeared at the end of the pre-transition period. Computer plotted distributions of post-transition licks (timed with respect to the last pre-transition lick) were examined while the horizontal or vertical distance between spouts was increased. Growing spout separation changed the height but not the timing of the modes of the post-transition lick distribution. This phase-locked synchronization of pre- and post-transition licks indicates that the central timing network of the lick generator is not reset but continues to run during transition between spouts and that the cessation of tongue movements is due to inhibition of the intracycle pattern generator and motor output. It is concluded that more sensitive recording techniques are required to detect the activity of the central timing network in absence of overt licking.
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  • 60
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    Experimental brain research 71 (1988), S. 611-617 
    ISSN: 1432-1106
    Keywords: Retina ; Projection ; Development ; Rat ; Rabbit
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We traced the retino-retinal projection with Rhodamine B isothiocyanate (RITC), Rhodamin labelled latex microspheres (RLM), horseradish peroxidase (HRP) and choleratoxin conjugated horseradish peroxidase (BHRP). The number and distribution of ganglion cells projecting to the contralateral eye were recorded. Newborn and young rats have up to about 130 ganglion cells projecting to the other retina; this confirms previous findings. We extended these findings in two ways. First, we describe a similar projection in rabbits consisting of fewer cells; second, we describe the persistence of a small component of this projection into adulthood. In addition we show with RITC and Nuclear Yellow double tracing that some of the retino-retinal ganglion cells have an axon collateral which projects to the superior colliculus. We performed control experiments in order to exclude spillover of tracer which might produce false positive labelling.
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  • 61
    ISSN: 1432-1106
    Keywords: Galanin ; Spinal cord ; Flexor reflex ; Intrathecal ; Cutaneous afferents ; Thermoreceptors ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The neuropeptide galanin (GAL) was injected intrathecally (i.t.) in decerebrate, spinalized, unanesthetized rats and its effect on the nocifensive flexor reflex was examined. The reflex, which was evoked by intense mechanical or thermal stimulation of the foot, was recorded from the ipsilateral hamstring muscles. I.t. GAL increased reflex excitability significantly more to thermal than to mechanical stimuli. It is suggested that GAL, which is present in sensory fibers that innervate the skin, is released by the central terminals of cutaneous afferents that are much more sensitive to thermal than to mechanical stimuli.
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  • 62
    ISSN: 1432-1106
    Keywords: Hypoglossal nucleus ; Biogenic amines ; Immunocytochemistry ; Tyrosine hydroxylase ; Serotonin ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The distribution of biogenic amines in the rat hypoglossal nucleus (nXII) was investigated with immunocytochemical methods using antibodies to tyrosine hydroxylase (TH) as a marker for catecholamines, and to 5-hydroxytryptamine (5-HT), the principal indoleamine, at the light microscopic level. TH and 5-HT immunoreactivity were found throughout all regions of nXII. Although the innervations overlapped, clearly differnt patterns of distribution were observed. TH immunoreactivity was localized primarily in the ventromedial quadrant of the caudal half of nXII and appeared largely as perisomatic-like profiles. In contrast, 5-HT immunoreactivity was greatest dorsally along the caudal half of nXII, although secondary foci of staining were evident ventrolaterally and, to a lesser extent, ventromedially. A perisomatic-like pattern of termination was observed for 5-HT in both dorsal and ventral regions of nXII. Since ventral and dorsal districts of nXII contain motoneurons that innervate protrusor and retrusor tongue muscles, respectively, we propose that the overlapping, yet differential distributions of catecholamines and indoleamines are important in controlling the relationships between functionally related groups of nXII motoneurons. These findings are discussed in relation to oro-lingual motor dysfunction.
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  • 63
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    Experimental brain research 73 (1988), S. 393-401 
    ISSN: 1432-1106
    Keywords: Rat ; Ganglion cell axons ; Regeneration ; Chemically defined media ; Fluorescent tracers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The potential for regeneration of adult rat ganglion cell (RGC) axons was investigated in vitro. Explants from RITC (rhodamine-B-isothiocyanate) retrogradely labeled and in vivo axotomized retinae were placed on dishes coated with various substrates. The retinal pieces were cultivated in a serum-free medium and incubated under 50 to 80% O2-enriched and 5% CO2-containing atmosphere. Under these conditions, massive outgrowth of fibers was observed as early as 24 h after explantation and over a period of time extending up to 7 days in culture. By various criteria, two main types of processes could be characterized: (1) Short, thick processes emerged from either migrated flat cells or from cells inside the retinal explant, and (2) long and thin processes emerged from cells in the ganglion cell layer (GCL). By immunohistochemistry, the short processes and the cells from which they had emerged, appeared to be glial acidic fibrillary protein (GFAP)-positive Thy 1 and L 1-negative, suggesting their glial nature. The second type of long, thin processes appeared to be GFAP-negative, L1- and Thy 1-positive, indicating that they were neuronal, probably RGC processes. Proof that long fibers emerged from RGCs was provided by retrograde labeling of RGCs with RITC prior to explanation. Numerous RITC-filled RGCs survived in vitro. Regrowing axons retransported part of the accumulated fluorescent dye in the orthograde direction and thus unequivocally permitted their identification as RGC axons. The fact that adult RGC axons can reelongate in vitro might provide a useful bioassay for investigations on the factors that either support or inhibit regrowth of axons from CNS neurons.
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  • 64
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    Experimental brain research 69 (1988), S. 417-423 
    ISSN: 1432-1106
    Keywords: Nucleus reticularis tegmenti pontis ; Vestibular ; Flocculus ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Forty-nine neurons were recorded in the nucleus reticularis tegmenti pontis (NRTP) during horizontal vestibular and/or optokinetic stimulation in immobilized pigmented rats. During optokinetic stimulation, the response of NRTP neurons was either unidirectional (51%) or bidirectional (49%). Histological reconstruction showed that unidirectional neurons were located in the dorsal-medial part of NRTP, and bidirectional neurons in the lateral part. All neurons exhibited a response during pure vestibular sinusoidal stimulation in the frequency range 0.025 Hz-0.2 Hz. NRTP neurons were divided into two groups according to their threshold to vestibular stimulation. Group A neurons had a low threshold, a low spontaneous activity and their firing frequency slowly increased with acceleration. Group B neurons showed opposite characteristics. Phase and gain analysis suggested that NRTP neurons carry a head velocity signal. After hemiflocculectomy, the gain of the vestibular response of contralateral NRTP neurons increased. From these data, the role of NRTP in the horizontal vestibulo-oculomotor is discussed.
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  • 65
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    Experimental brain research 70 (1988), S. 155-165 
    ISSN: 1432-1106
    Keywords: Sm1 cortex ; Receptive fields ; Rat ; Bilateral receptive fields ; Hindlimb
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Single cells in the primary somatosensory (Sm1) cortex were investigated for responses to bilateral hindpaw stimulation in Wistar rats anaesthetised by continuous intravenous administration of Althesin. Fifty-one percent of cells sampled (N = 134) responded to equivalent punctate mechanical stimuli delivered to both the contralateral and ipsilateral hindpaws under light anaesthesia. The distribution by cortical depth of cells with receptive fields (RFs) on both hindpaws was not significantly different from cells which had only contralateral RFs. No cell was found with a purely ipsilateral RF. For 86% of cells tested (N=44) the ipsilateral RF was partly or completely homologous with areas within the contralateral RF. The sizes of ipsilateral RFs were smaller on 66% of occasions when tested against their contralateral RFs. Modal latencies to ipsilateral mechanical stimulation were longer than to contralateral stimulation (34.1±9.1 ms (S.D) cf. 26.4±7.2 ms, N=44). Ipsilateral RFs were lost for 77% of cells tested following a 33% increase in anaesthetic infusion rate. Conditioning mechanical stimuli applied to the centre receptive field (CRF) on the ipsilateral hindpaw reduced or abolished a cell's responses to equivalent test stimuli applied to it's contralateral CRF with C-T intervals of 20–200 ms. Conditioning stimuli applied to the CRF contralateral to the cell reduced or abolished responses to test stimuli on the cell's ipsilateral CRF using C-T intervals of 0–900 ms. Responses in one cortex to stimulation of the ipsilateral hindpaw were unaffected by elimination of responses from the same hindpaw in the opposite contralateral Sm1 cortex, where responses had been suppressed by topical Lignocaine administration. Retrograde transport of horseradish peroxidase from hindpaw Sm1 cortex labelled many cells in homolateral thalamus, but failed to label cells in the entire forebrain contralateral to the injection site. It is concluded that direct crossed thalamocortical and callosal Sm1-Sm1 pathways do not contribute to the production of hindpaw ipsilateral receptive fields.
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  • 66
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    Experimental brain research 72 (1988), S. 443-449 
    ISSN: 1432-1106
    Keywords: Protein kinase C subspecies ; Immunocytochemistry ; Visual cortex ; Hippocampus ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Monoclonal antibodies against type II and type III subspecies of protein kinase C PkC(II/III) were used to map the distribution of these isoenzymes in the visual cortex (area 17), hippocampus and dentate gyrus of the rat. PkC(II/III)-immunocytochemistry resulted in a specific staining of neuropil and of neuronal somata with their proximal dendrites. The majority of immunopositive cells exhibited a punctate distribution of reaction product, while only a few neurons were homogeneously labeled. In the visual cortex stained neurons were distributed throughout all laminae and reached a particularly high density in layers II/III. Moreover, PkC(II/III)-positive neurons were found within the strata pyramidale and radiatum of the hippocampus proper and in the stratum granulosum, the subgranular zone and the hilar region of the dentate gyrus. The present results suggest that PkC(II/III)-positive neurons constitute a distinct population of both projection and local circuit neurons that are not exclusively associated with any one neurotransmitter system.
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  • 67
    ISSN: 1432-1106
    Keywords: Neostriatum ; Substance P ; Immunocytochemistry ; Golgi-impregnation ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Substance P-immunoreactive boutons were examined in the electron microscope in sections of the rat neostriatum that contained retrogradely labelled striatonigral neurons and/or Golgi-impregnated medium-size densely spiny neurons. The postsynaptic targets of the immunoreactive boutons were characterized on the basis of ultrastructural features, their projection to the substantia nigra and/or their somato-dendritic morphology. Substance P-immunoreactive axonal boutons formed symmetrical synaptic specializations. Of a total of 233 randomly identified synaptic boutons 72.5% made contact with dendritic shafts, 15% with dendritic spines and 10.7% with perikarya. The ultrastructural characteristics of some of the postsynaptic neuronal perikarya were consistent with their identification as striatal interneurons. Similarly, the observation of some of the substance P-containing terminals in contact with spines, spine-bearing dendritic shafts and perikarya with the ultrastructural characteristics of medium-size densely spiny neurons suggested that one of the targets of substance P-positive terminals are striatal projection neurons. Direct evidence for this was obtained in sections from rats that had received injections of horseradish peroxidase conjugated with wheatgerm agglutinin in the substantia nigra. The perikarya of retrogradely labeled striatonigral neurons were found to receive symmetrical synaptic input from substance P-positive boutons. Ultrastructural analysis of Golgi-impregnated medium-size densely spiny neurons, some of which were also retrogradely labeled from the substantia nigra, demonstrated directly that this class of neuron was postsynaptic to the substance P-immunoreactive boutons. The combination of Golgi-impregnation with substance P-immunocytochemistry made it possible to study the pattern or topography of the substance P-positive input to medium size densely spiny neurons. The substance P-containing boutons made contact predominantly with perikarya and dendritic shafts. This pattern of input is markedly different from that of other identified inputs to medium-size densely spiny neurons.
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  • 68
    ISSN: 1432-1106
    Keywords: Extracellular Na+ concentration ; Quisqualate (quis) ; N-methyl-D-aspartate (NMDA) ; Tetrodotoxin (TTX) ; Hippocampal area CA1 ; Rat ; Extracellular Ca2+ concentration ; Extracellular Mg2+ concentration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Decreases in extracellular sodium concentration ([Na+]o) and associated slow negative field potentials (fp's) were monitored with double barreled sodium sensitive/reference microelectrodes in area CA1 of rat hippocampal slices during iontophoretic application of the glutamate receptor agonists N-methyl-D-aspartate (NMDA) and quisqualate (quis). The effects of lowering [Ca2+]o on these signals were compared to those of lowering [Mg2+]o. Both NMDA- and quis-induced decreases in [Na+]o of up to 60 mM and in the fp's of up to 8 mV. Decreasing [Mg2+]o enhanced NMDA-induced signals, whereas quis-induced signals were unaffected. Lowering [Ca2+]o also enhanced NMDA signals, although somewhat less than lowering [Mg2+]o. This effect was still present, even when voltage dependent Na+ currents were blocked by 10-7 tetrodotoxin. Interestingly, quis-induced signals could be enhanced in a low Ca2+ medium as well, but only when high quis concentrations were used. The results suggest that, during the sorts of large decreases of [Ca2+]o observed during seizure activity, activation of NMDA receptors is facilitated.
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  • 69
    ISSN: 1432-1106
    Keywords: Dorsal lateral geniculate nucleus ; Horseradish peroxidase ; Retinal axons ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Retinal endings in the dorsal lateral geniculate nucleus (dLGN) of the rat were visualized by anterogradely transported horseradish peroxidase following injections in the optic tract. The morphological findings confirm the two types of retinal axons previously suggested by Golgi investigations. In the caudal third of the dLGN type 2b axons, with small dense clusters of boutons, are the only representatives of retinal fibres seen. In the rostral two thirds they are intermingled with the larger type 2a terminals, but tend to accumulate laterally, adjacent to the optic tract. This study supports the concept that large retinal ganglion cells probably give rise to 2a axons that may represent a Y-like channel, whereas 2b axons are derived from small ganglion cells, and may relay a W-like pathway.
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  • 70
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    Experimental brain research 72 (1988), S. 71-82 
    ISSN: 1432-1106
    Keywords: Cholinergic-specific ganglioside ; Cholinergic neurons ; Chol-1 ; Spinal cord ; Brain ; Retina ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Previous work from this laboratory has identified gangliosidic surface markers specific for cholinergic neurons. Antibodies to these markers, collectively designated Chol-1, induce complement-mediated lysis of the cholinergic subpopulation of synaptosomes and provide the basis for a new immunocytochemical method for staining cholinergic neurons in rat, guinea pig and human material. The specification and localization of immunocytochemical staining for Chol-1 was investigated in selected areas of the rat central nervous system. The antigen was typically expressed on all neurons previously identified as being cholinergic using monoclonal antibodies to choline acetyltransferase. At spinal levels Chol-1 was present on large and smaller cell bodies in the ventral horn motoneuron area. The preganglionic sympathetic neurons in the thoracic intermediolateral nucleus were also Chol-1-positive. Nerve terminal-like staining was observed in association with stained large Chol-1 positive and smaller unstained Chol-1 negative neurons, and in lamina I and III of the dorsal horn. In the mesencephalon, motoneurons of the oculomotor and trochlear nucleus, as well as neurons within the pedunculopontine tegmental nucleus and the red nucleus were Chol-1-positive. In addition visceromotoneurons of the Edinger-Westphal nucleus were stained with anti Chol-1 antibodies. In the basal forebrain the antibodies gave a positive reaction on well known cholinergic neurons in the vertical and horizontal limbs of the diagonal bands of Broca and the medial forebrain bundle. In agreement with studies using antibodies to choline acetyltransferase, a small sub-population of neostriatal neurons (1–2%) was Chol-1-positive. In the rat retina, both anti-Chol-1 and anti-choline acetyltransferase antibodies gave rise to a nerve terminal-like staining in the same bands within the inner plexiform layer. The anti-Chol-1 antibodies also stain normal and pathological human material and could have a useful application in human neuropathology.
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  • 71
    ISSN: 1432-1106
    Keywords: AP5 ; NMDA antagonist ; Hippocampus ; DRL ; Memory ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Rats were trained to lever press on a differential reinforcement of low rates (DRL-18 s) schedule. They were then allocated to four treatment groups. These were: hippocampal aspiration lesions [HIPP]; implantation of osmotic minipumps for intraventricular infusion of either (a) the NMDA receptor antagonist 30 mM D, L-2-amino-5-phosphonopentanoic acid [AP5] or (b) vehicle [VEH]; and an unoperated control group [UNOP]. In subsequent DRL testing, the HIPP group showed a profound and enduring loss of efficiency, resulting from an increased tendency to respond too early; the AP5 group showed a qualitatively similar, but less severe, impairment followed by full recovery once the minipumps had expired; the VEH and UNOP groups both maintained their pre-operative levels of efficiency. We conclude that AP5 infusion disrupts temporary memory storage in the hippocampus, and that the hippocampus is concerned with the retention of memories outside the purely spatial domain.
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  • 72
    ISSN: 1432-1106
    Keywords: Neurotransmitter ; Immunohistochemistry ; 3-D reconstruction ; Confocal microscopy ; Rat ; Lamprey
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A new method for three-dimensional reconstruction of transmitter-identified neurons is presented which involves “en bloc” immunofluorescence histochemistry and confocal scanning microscopy. The technique was applied to different types of neurons in the rat brain and lamprey spinal cord. Thick sections or tissue “blocs” (50–200 μm thick) were incubated with antisera against neuropeptides or monoaminergic markers, followed by fluorescent secondary antibodies. Three-dimensional reconstructions were obtained by scanning the preparations in sequential focal planes with a thin laser beam, while sampling the emitted light in each focal plane. The method is convenient and can be applied to a wide variety of neuron types. The reconstructions obtained are accurate since the “optical serial sections” of the specimen are perfectly aligned, and optic disturbances such as “halo” phenomena do not occur.
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  • 73
    ISSN: 1432-1106
    Keywords: Adult hypothyroidism ; Dendritic spines ; Pyramidal cells ; Cerebral cortex ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We have previously shown (Ruiz-Marcos et al. 1980, 1982) that thyroidectomy (T) performed in rats at 40 days of age, well past the neonatal period of development, results by 80–90 days of age in a decrease of the number of spines along the shaft of pyramidal neurons with the cell body in layer V in the visual area of the cerebral cortex. We have here studied how soon after the operation an effect on spine number and distribution may be observed. We have found that the response of these neurons to T is very rapid: a decrease in the number of spines/shaft between T and age-paired controls (C) rats is statistically significant by the earliest period of observation, namely 5 days after T. These results may be related to those of Dembri et al. (1983) showing that T performed in adult rats decreases the activity of Type I RNA polymerase by 5 days after the operation. It is possible that T impairs the synthesis of some compound(s) necessary for the formation and maintenance of spines. The present results suggest that spine number is not a fixed structure of the apical shaft once brain development is over, but is in a state of continuous formation and degradation. We have further observed that the effect of T performed at 40 days of age is more pronounced in the distal part of the shaft than on the rest, a result similar to that found after neonatal T (Ruiz-Marcos et al. 1982). However, contrary to findings after early hypothyroidism, T at 40 days of age does not distort the distribution of spines along the shaft.
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  • 74
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    Experimental brain research 71 (1988), S. 291-297 
    ISSN: 1432-1106
    Keywords: ACTH ; Emotional response ; Motor activity ; Vasopressin ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In an attempt to find whether vasopressin (VP) secretion is suppressed by learned emotional stress, we have given rats under a hypertonic condition simultaneously applied light and tone that had been paired previously with footshocks and have quantified immunoreactive VP (ir-VP) in the plasma. In a training session light (60 watt) and tone (2 kz) of 3-s duration which were paired with electric footshocks (50 Hz, 1-s duration) were given to rats 11 times at an interval of 30 s. Various lengths of time after the training, the rats were tested with light and tone, which were unpaired with footshocks and repeatedly applied every 15 s for 3 min in the box used for training. Hypertonic NaCl (0.5 M, 2 ml/ 100 g b. w.) was injected s. c. 30 min before testing to increase the basal level of plasma VP. After testing, plasma ir-VP was significantly less in the experimental group than in the 0-mA control group of rats that were trained without FS. The values for the experimental group were also significantly less than those of untested control rats that had been trained with FS but were not tested. Plasma osmolality and blood haemoglobin concentration were not significantly different between control and experimental groups. Plasma immunoreactive adrenocorticotrophic hormone (ir-ACTH) level was higher and motor activity as expressed by cumulative time period of body movement during testing was lower in the experimental group than in either of the control groups. The difference in plasma ir-VP between experimental and control groups was statistically significant two days but not seven days after training, whereas ACTH and motor activity in experimental groups were still significantly different from those in control groups seven days after training. The suppressive VP and augmentative ACTH responses to testing disappeared in the rats that had received light and tone repeatedly during the intervening period between training and testing. These data support the hypothesis that emotional stimuli suppress VP secretion.
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  • 75
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    Experimental brain research 72 (1988), S. 178-184 
    ISSN: 1432-1106
    Keywords: Choline acetyltransferase ; Immunocytochemistry ; Substantia nigra ; Pedunculopontine tegmental nucleus ; Acetylcholine ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Putative cholinergic axons and synaptic endings were demonstrated in the substantia nigra (SN) of the rat by light and electron microscopy on the basis of the localization of choline acetyltransferase (ChAT) immunoreactivity. The distribution of ChAT immunoreactivity in the SN as demonstrated by light microscopy revealed a modest network of ChAT-immunoreactive beaded axons in the SNc, in comparison to a relatively sparse distribution in the SNr. These axonal profiles were most dense in the middle of the rostral-caudal extent of the SNc and appeared to be concentrated in the middle third of the medial-lateral extent. By electron microscopy, unmyelinated, small diameter (0.25 μm) ChAT-immuno-reactive axons were observed interspersed among numerous other non-immunoreactive axons in the SNc. ChAT-immunoreactive synaptic endings were observed in juxtaposition to small caliber (0.5 μm) non-immunoreactive dendrites, and contained numerous spheroidal synaptic vesicles and occasional mitochondria. Synaptic contact zones were characterized by an accumulation of synaptic vesicles along the presynaptic membrane, and a prominent postsynaptic densification producing an asymmetrical pre-/postsynaptic membrane profile typical of excitatory synapses. These findings provide direct evidence for a cholinergic innervation of the SN, and suggest that this input may have an excitatory effect on neuronal elements in the SNc.
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  • 76
    ISSN: 1432-1106
    Keywords: Microglia ; Dorsal horn ; Nerve lesion ; Light microscopy ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effect of peripheral nerve transection on the size of the microglial cell population in cytoarchitecturally distinct regions of the spinal cord dorsal horn of rats was evaluated at selected intervals 2 through 35 days after unilateral brachial plexotomy. The identification of cells was verified by electron microscopic examination of a representative random sample of cells included in the counts. Microglial cell numbers were increased in laminae I, II as well as the arbitrarily defined deeper laminae 3.5 days after surgery. Although microglial cell numbers in laminae I were within normal range 35 days after axotomy, those of the more ventrally located laminae remained significantly greater than control values for the duration of the experimental period. These findings demonstrate that: 1) microglial cell proliferation in the dorsal horn is an early event in the central changes that are attendant to peripheral nerve injury 2) the time course of the response varies in cytoarchitecturally different regions.
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  • 77
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    International journal of biometeorology 32 (1988), S. 17-20 
    ISSN: 1432-1254
    Keywords: Epilepsy ; Electromagnetic fields ; Rat ; Audiogenic seizure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Geography , Physics
    Notes: Abstract In order to study the possible association between epileptic seizures and natural electromagnetic fields, 32 female audiogenic seizure (AGS)-susceptible rats were exposed to simulated 10 kHz and 28 kHz atmospherics and to a sinusoidally oscillating magnetic field with a frequency of 100 Hz and field strength of 1 A/m. After the electromagnetic exposure, seizures were induced in the rats with a sound stimulus. The severity of the seizure was determined on an ordinal scale, the audiogenic response score (ARS). The time from the beginning of the sound stimulus to the onset of the seizure (seizure latency) and the duration of the convulsion was measured. No differences from the control experiments were found in the experiments with simulated atmospherics, but the 100 Hz magnetic field increased the seizure latency by about 13% (P〈0.02). The results do not support the hypothesis that natural atmospheric electromagnetic signals could affect the onset of epileptic seizures, but they suggest that AGS-susceptible rats may be a useful model for studying the biological effects of electromagnetic fields.
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  • 78
    ISSN: 1432-1254
    Keywords: Atmospherics ; Carrageenan inflammation ; Rat ; Susceptibility ; Correlations
    Source: Springer Online Journal Archives 1860-2000
    Topics: Geography , Physics
    Notes: Abstract Between the mean daily density of 28 kHz atmospherics and the onset of epileptic fits there is a highly significant correlation coefficient (r) of 0.30; there is a negative coefficient of −0.20 between the fits and the mean daily density of 10 kHz atmospherics. The onset of heart infarction is correlated with 28 kHz atmospherics (r=0.15). Furthermore, we have discovered that sudden deafness is also correlated with certain configurations of atmospherics. In this paper we report the following correlation coefficients between the inflammatory reaction of rats to a carrageenan injection (rci) into a hind paw and the mean daily pulse rate of atmospherics of the same day:r=0.49 for the 8 kHz atmospherics (P〈0.02) andr=0.44 for the 10 kHz atmospherics (P〈0.04). The correlations between rci reaction and other atmospherics (12 and 28 kHz) are smaller and not significant. By the method of multiple linear regression we found a multipleR=0.54 between rci reaction and the 8 and 10 kHz atmospherics (the regression function for the rci reaction is 0.15+0.004×8 kHz+0.002×10 kHz,P〈0.05).
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  • 79
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    Naunyn-Schmiedeberg's archives of pharmacology 338 (1988), S. 463-471 
    ISSN: 1432-1912
    Keywords: 8-OH-DPAT [8-hydroxy-2-(di-n-propylamino)tetralin] ; 5-HT1A receptors ; CNS ; 5-HT synthesis and release ; Hemitransection ; Dorsal raphé application ; Regulation of 5-HT activity ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The present study was undertaken in an attempt to assess whether the effects of the potent and selective 5HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin, 8-OH-DPAT, on cerebral 5-hydroxytryptamine (5-HT) neurochemistry in vivo are mediated via 5-HT autoreceptors on the cell bodies or on the terminals, and/or via postsynaptic 5-HT receptors. To this end we determined in vivo indices of 5-HT synthesis and release/turnover rates in a number of prominent 5-HT neuronal projection areas in the CNS i) after systemic administration of 8-OH-DPAT to rats with an acute unilateral axotomy of the ascending mesencephalic monoamine neurones, or ii) after local infusion of the compound into the dorsal raphé (DRN) 5-HT cell body region of intact rats. Transection did not alter 5-HT synthesis per se, but prevented the synthesis-inhibitory effect of 8-OH-DPAT. Thus, the 5-HT synthesis-inhibiting action of 8-OH-DPAT is highly dependent upon intact impulse flow in the central 5-HT neurones. On the other hand, local DRN application of the compound (1 μg) resulted in a clearcut reduction of the 5-HT synthesis and release indices measured in 5-HT terminals in, e. g., the striatum. These findings provide direct neurochemical evidence that by preferentially stimulating somatodendritic 5-HT1A receptors, 8-OH-DPAT inhibits the 5-HT neuronal impulse flow, thereby effectuating decreased terminal 5-HT synthesis and release. Taken together, the data are consistent with the suggestion that 8-OH-DPAT acts as an agonist preferentially at cell body vs. terminal 5-HT autoreceptors, therefore also emphasizing the distinction between terminal and cell body 5-HT autoreceptors. The results obtained may have important implications for the understanding of mechanisms involved in regulating the activity of central serotoninergic neurones.
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  • 80
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    Naunyn-Schmiedeberg's archives of pharmacology 338 (1988), S. 287-292 
    ISSN: 1432-1912
    Keywords: PYY ; Rat ; Non-adrenergic ; Non-cholinergic ; In vitro ; Small intestine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effects of peptide YY (PYY) on motor activity of the rat small intestine, were studied using isolated organ bath preparations arranged for recording muscle activity in the longitudinal axis. PYY induced TTX sensitive concentration-dependent contractions and/or relaxations of the longitudinal muscle in different regions of the small intestine. In the duodenum PYY evoked only “cholinergic” contractions (3 × 10−8−3 × 10−7 M). In the jejunum, PYY-evoked concentrations were non-cholinergic, and contractions were never seen in the ileum. In the jejunum and ileum, PYY-evoked relaxations (3 × 10−3 × 10−7 M) were unaffected by adrenoceptor or cholinergic receptor blockade, thus indicating that these relaxations were mediated by non-adrenergic, non-cholinergic (NANC) inhibitory nerves. Another action of PYY was to cause inhibition of field stimulation-evoked cholinergic concentrations. This inhibitory action was primarily due to antagonism of post-junctional, cholinergic receptor mediated events. In addition, PYY inhibited histamine evoked contractions of the longitudinal muscle. All regions of the small intestine could be desensitized to PYY. Such PYY-densensitization did not affect the ability of the longitudinal muscle to relax in response to applied ATP or papaverine. These results suggest PYY has potent concentration-dependent stimulatory actions at intrinsic inhibitory and excitatory motor nerves. In addition, PYY interferes with contractions but not relaxations of the longitudinal muscle.
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  • 81
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    Psychopharmacology 95 (1988), S. 344-350 
    ISSN: 1432-2072
    Keywords: Anticholinergic drug effect ; Age drug sensitivity ; Environmental interaction ; Grooming ; Social investigation ; Social grooming ; Agonistic interactions ; Play fighting and immobility ; Reintroduction procedure ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The modulation of spontaneous (social and individual) behaviour as a function of the age of the rat (1, 3, 6, 12, 18 and 24 months) and of scopolamine dose (0.1, 0.2, 0.3 and 0.5 mg/kg) was studied. Observations were conducted during the dark phase of the reverse light/dark schedule using a reintroduction procedure. Results showed a marked effect of scopolamine on most of the behavioural patterns considered. Environmental interaction was enhanced whilst agonistic and social active interactions (social grooming) and play fighting were reduced by the drug. A slight hyposensitivity in the youngest rats and a marked hyposensitivity to the drug in the oldest ones were observed. The relationship to biochemical data and human sensitivity on the one hand and to learning and memory tasks and cholinergic specificity on the other hand, are discussed.
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  • 82
    ISSN: 1432-2072
    Keywords: Drug discrimination ; Cocaine ; Tolerance ; CNS stimulants ; Rat ; Amphetamine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rats were trained to discriminate cocaine, 10.0 mg/kg, using a two-lever operant procedure. Dose-effect data were determined for the substitution of cocaine, diethylpropion, methylphenidate, phenmetrazine, phentermine, and fenfluramine for the cocaine stimulus. All of these drugs, except fenfluramine, substituted fully for the cocaine stimulus. Subsequently, training was halted and cocaine, 20 mg/kg/8 h, was administered for 9 days, and dose-effect data were redetermined for all of these drugs on days 7–9 of chronic administration. Chronic administration of cocaine produced tolerance to the stimulus properties of cocaine, and cross-tolerance to the stimulus properties of methylphenidate, phenmetrazine, and phentermine, such that doses approximately two-fold higher than those used acutely were necessary to reproduce the original effect; the potency for the substitution of diethylpropion for the cocaine stimulus was decreased greater than four-fold; and fenfluramine still failed to substitute for the cocaine stimulus. These data suggest that 1) a common mechanism may mediate tolerance to the discriminative stimulus properties of cocaine, methylphenidate, phenmetrazine, and phentermine, and 2) tolerance in the drug discrimination procedure may have potential for establishing a comprehensive evaluation of dependence liability of CNS stimulants.
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  • 83
    ISSN: 1432-2072
    Keywords: LY 171555 ; SKF 38393 ; Combined D1 and D2 stimulation ; SCH 23390 ; D1 supersensitivity ; Locomotor activity ; Grooming ; Stereotyped behaviour ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The selective D1 receptor stimulant SKF 38393 dose-dependently increased grooming time in rats without affecting locomotor activity or eliciting stereotyped behaviour. The selective D2 receptor agonist LY 171555 induced a dose-dependent increase in rat motility, a marked decrease in grooming time and a low occurrence of stereotyped behaviour. Concurrent administration of the two selective agonists induced high-degree stereotyped responses and reductions in locomotor and grooming behaviours. Rats withdrawn from repeated treatment with the selective D1 receptor blocker SCH 23390 (0.05 mg/kg twice daily for 21 days; 7 days of washout) did not exhibit any change of locomotor and grooming responses to threshold doses of LY 171555 and SKF 38393 given alone or in combination. On the contrary, a significantly greater occurrence of high-degree stereotyped responses to the combination of the two selective agonists was observed. The data support the view that D1 and D2 receptors have a cooperative role in the generation of stereotypies and suggest that D1 receptor supersensitivity needs D2 stimulation to be revealed.
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  • 84
    ISSN: 1432-2072
    Keywords: 8-OH-DPAT ; Feeding ; Drinking ; Palatability ; Appetite ; Fenfluramine ; Satiety ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The 5-HT1A agonist 8-OH-DPAT, at a dose of 30 μg/kg, enhanced the consumption of sweetened wet mash and sweetened milk in non-deprived rats. In partially satiated rats, sensitivity to the hyperphagic effect of 8-OH-DPAT on wet mash intake was substantially increased, so that the minimally effective dose was reduced to 3 μg/kg. Similarly, 8-OH-DPAT was more efficacious in increasing milk intake in satiated rats. Thus, 30 and 40 μg/kg 8-OH-DPAT produced a 4-fold increase of milk intake in completely satiated rats compared to a 2-fold increase in partially satiated animals at a dose of 30 μg/kg. The increased intake of liquid and wet mash diets observed after treatment with low doses of 8-OH-DPAT argues against the involvement of non-specific gnawing in the increased consumption of solid food produced by the drug. Rather, the data suggest that 8-OH-DPAT may specifically stimulate appetite by counteracting a tonic serotonergic inhibition of feeding. The present experiments also showed that 8-OH-DPAT attenuates fenfluramine-induced anorexia which is thought to depend on increased serotonergic neurotransmission.
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  • 85
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    Psychopharmacology 96 (1988), S. 174-180 
    ISSN: 1432-2072
    Keywords: Aging ; Short-term memory ; Delayed response ; Delayed matching ; Delayed non-matching ; Arecoline ; Physostigmine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Separate groups of rats of three ages (6 month, 15 month or 24 month) were trained in a two-lever operant chamber on one of two versions of a paired-trial delayed response task involving either matching or non-matching of the choice response to a sample lever. The older rats were unimpaired in learning either version of the task during initial training with no (0 s) delay between the sample and choice responses. However, when variable 0–24 s delay intervals were introduced, the 24-month group was impaired on acquisition of the delayed non-matching task, and both the 15- and 24-month groups were impaired on acquisition of the delayed matching task compared to the 6-month group. Deficits in the older groups in asymptotic performance were attributable to an impairment at longer delay intervals whilst maintaining near perfect performance at the shorter delay intervals, suggesting a selective short-term memory impairment. The delay-dependent deficits of the older groups were not ameliorated by the muscarinic agonist arecoline or the cholinesterase inhibitor physostig-mine, and so failed to corroborate a cholinergic interpretation of the observed age-related impairment in short-term memory.
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  • 86
    ISSN: 1432-2072
    Keywords: Benzodiazepine ; Diazepam ; Beta-carboline ; FG 7142 ; RO 15-1788 ; Schedule-induced polydipsia ; SIP ; Adjunctive behavior ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Although benzodiazepine agonists and inverse agonists have opposite effects on drinking elicited by water deprivation, there is much less information about the effects of these drugs on nonhomeostatic drinking. In this experiment the effects of diazepam (0.3–5.0 mg/kg), a benzodiazepine receptor agonist, and FG 7142 (1.0–9.0 mg/kg), an inverse agonist, were determined on drinking elicited by a FT-60 schedule of food delivery (SIP). Both diazepam and FG 7142 dose-dependently reduced SIP, measured as either licking or volume consumed. In addition, diazepam reduced panel pressing for food, decreased locomotor activity, and changed the time course of each behavior. In contrast, FG 7142 reduced schedule-induced drinking without significantly altering other behaviors. The antagonist RO 15-1788, when given in combination with these drugs, only partially restored the reductions in licking produced by diazepam, but was much more effective in reversing the effects of FG 7142 at doses of the antagonist that failed by themselves to affect responding. The opposite pattern of effects was seen on the volume of water consumed. These effects are discussed in terms of the behavioral and pharmacological specificity of these drugs.
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  • 87
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    Psychopharmacology 94 (1988), S. 115-118 
    ISSN: 1432-2072
    Keywords: Clozapine cue ; Drug discrimination ; Acetylcholine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rats were trained to discriminate clozapine (CLZ; 5.76 mg/kg, IPt-30 min) in a two-lever operant task in which responding on the correct lever was reinforced with water under a fixed ratio 32 schedule. The ED50 of CLZ was 1.1 mg/kg. The CLZ cue was generalised to atropine (ED50=8.7 mg/kg), scopolamine (ED50=0.37 mg/kg) and fluperlapine (ED50=4.0 mg/kg), but not to non-cholinergic compounds, i.e. buspirone, diazepam, ketanserin, prazosin or SCH 23390. The peripherally-acting muscarinic antagonist methylscopolamine did not substitute for CLZ. Furthermore, the CLZ cue was marginally attenuated byd-amphetamine; a high dose of oxotremorine (1 mg/kg) appeared to block the CLZ cue (to 22%). However, this effect could not be evaluated statistically due to an insufficient number of animals responding. These results may indicate that the discriminative stimulus effects of CLZ primarily involve antagonism of central muscarinic acetylcholine receptors.
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  • 88
    ISSN: 1432-2072
    Keywords: Amygdala ; Corticotropin releasing factor ; Exploration ; Memory modulation ; Open field ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of intra-amygdala injections of corticotropin-releasing factor (CRF) on memory and exploratory behavior in rats were examined in the present study. Rats with chronically implanted cannulae received intra-amygdala injections of vehicle or CRF at a dose of 0.01, 0.1 or 1.0 μg, either immediately after the inhibitory avoidance training or prior to the open field activity test. Results indicated that while CRF at low (0.01 μg) and high (1.0 μg) doses produced no significant effect on retention or exploration, immediate post-training intra-amygdala injections of CRF at the medium dose (0.1 μg) significantly improved retention of the inhibitory avoidance response. The same dose of CRF, given shortly prior to the open field activity test, decreased locomotor activity, rearing and hole-poke responses in rats. These results suggest that the amygdala is one of the anatomical loci involved in CRF modulation of memory processing and exploration in rats. The implication of CRF in mediating the influences of stress on behavior is discussed.
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  • 89
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    Psychopharmacology 96 (1988), S. 262-266 
    ISSN: 1432-2072
    Keywords: Alpha-melanotropin ; Inulin ; Blood-brain barrier ; Lipid solubility ; Pharmacokinetics ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The permeability of the blood-brain barrier (BBB) to immunoreactive alpha-melanotropin (α-MSH) was quantified in rats pretreated with monosodium l-glutamic acid to deplete their CNS stores of endogenous α-MSH. The methodology, suitable for poorly permeable substances, monitored blood and brain tissue concentrations of α-MSH over 15 min following intravenous injection of 30 nmol synthetic α-MSH. Rate constants for entry of α-MSH into brain tissue were estimated from separate nonlinear least-squares fits of connecting two- and one-compartment open models to plasma and extravascular brain tissue concentration data, respectively. Comparisons were made to rate constants measured similarly for 14C-inulin. The BBB had a low permeability to immunoreactive α-MSH, consistent with peptide penetrating the barrier by passive diffusion dependent upon the lipid solubility of the molecule.
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  • 90
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    Psychopharmacology 94 (1988), S. 133-137 
    ISSN: 1432-2072
    Keywords: Diazepam ; Haloperidol ; Domperidone ; 6-Hydroxydopamine ; DSP-4 ; Place conditioning ; Dopamine ; Noradrenaline ; Reward ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The conditioned place preference paradigm was used to investigate the neurochemical and neuroanatomical substrates which mediate the rewarding properties of diazepam. The results confirmed that diazepam (1 and 2.5 mg/kg, IP) produced place preference for a distinctive environment that had previously been paired with injections of the drug. Pretreatment with haloperidol (0.1 mg/kg) antagonised the place preference induced by diazepam (1 mg/kg). Pretreatment with domperidone (2 mg/kg) failed to influence this effect of diazepam. Haloperidol (0.1 mg/kg) and domperidone (2 mg/kg) alone did not produce place aversion. In separate experiments the diazepam-induced place preference was examined in rats having 6-hydroxydopamine (6-OHDA) lesions of the nucleus accumbens. These animals did not show preference for the compartment associated with diazepam. Depletion of central noradrenaline produced by systemic injections of DSP4 did not affect diazepam-induced place preference conditioning. These findings suggest that dopamine-containing neurons of the mesolimbic system are a component of the neural circuitry that mediates the reinforcing properties of diazepam.
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  • 91
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    Psychopharmacology 94 (1988), S. 161-166 
    ISSN: 1432-2072
    Keywords: Hangover ; Thermoregulation ; Tolerance ; Ethanol ; Stress ; Compensatory reactions ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The recent finding of rebound hyperthermia in rats on the day after a single IP injection or oral intubation of ethanol was confirmed. In our studies, body temperature measured by rectal probe was significantly decreased for 8 h after 2.5 g/kg ethanol IP and was then significantly elevated 16–24 h after injection; increased vocalization during handling at 24 h was also found. However, rats isolated in a sound-attenuation chamber with remote temperature measurement showed no hyperthermia even though they were hypothermic during intoxication. The results do not support the hypothesis that rebound hyperthermia was caused by either a disruption of circadian rhythms, or by a mild abstinence syndrome alone. Instead, it appears that external stimuli, perhaps related to stress or associated with ethanol administration, are necessary on the day after a moderate dose of ethanol to produce the hyperthermia. Like hangover in humans, hyperthermia was reduced in rats made tolerant to ethanol: both the hypothermia and the rebound hyperthermia were significantly lower on the day after the 12th alternate-day ethanol injection than after the first injection. The aftereffects in rats of acute intoxication are, by definition, hangover signs, and they resemble hangover in humans in several ways, but their relevance as an animal model of hangover remains to be determined.
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  • 92
    ISSN: 1432-2072
    Keywords: 5-Hydroxytryptophan ; Imipramine ; Brainstem auditory evoked response ; Middle latency auditory evoked response ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The neurophysiological effects of acute and chronic treatment with the tricyclic antidepressant drug imipramine were investigated. Brainstem (BAER) and middle latency (MLR) auditory evoked responses were monitored in the alert and immobile rat. Daily injection of imipramine (10 mg/kg, IP) for 2 weeks produced a 13% increase in the latency and a 35% reduction in the amplitude of the N17 component of the MLR. Acute imipramine treatment had no effect. There was no observable change in the BAER after either acute or chronic drug administration. Serotonergic function was assessed by studying the inhibitory effects of 5-hydroxytryptophan on the BAER and MLR. Chronic application of imipramine caused an apparent reduction of the effects of 5-hydroxytryptophan (75 mg/kg, IP) on the N17 component of the MLR. This may, however, be due to the shift in baseline latency and amplitude. Inhibition of the BAER by 5-hydroxytryptophan was unaltered by long term exposure to imipramine. Acute treatment with imipramine was without effect on the modulation of the BAER and the MLR by 5-hydroxytryptophan. These results provide evidence that chronic, as opposed to acute, administration of imipramine had an inhibitory effect on auditory processing at the level of the MLR and that this may be associated with a change in the net output of the serotonergic system.
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  • 93
    ISSN: 1432-2072
    Keywords: Benzodiazepines ; Triazolopyridazines ; Noradrenaline ; Clonidine ; Yohimbine ; Drug discrimination stimulus ; Fixed ratio performance ; Bicuculline ; Ro 15-1788 ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of clonidine on the antianxiety and sedation of benzodiazepines (BZD) were assessed respectively in rats trained in a two-lever diazepam cue discrimination procedure and in single-lever fixed-ratio (FR) water-reinforced performance. Clonidine (10–60 μg/kg) significantly shifted to the left the dose-effect curves of diazepam in the discrimination paradigm. This treatment also shifted generalization dose-effect curves of the diazepam cue to chlordiazepoxide and CL 218872 to the left in the drug discrimination procedure. The diazepam cue was antagonized in a dose-related manner by Ro 15-1788, but not by bicuculline. Clonidine also potentiated the rate-decreasing effects of diazepam on the FR schedule when the dose of diazepam was increased to 0.3 mg/kg, but not the milder rate-decreasing effect of CL 218872 until the dose of CL 218872 was increased to 10 mg/kg. The potentiating effects of clonidine on the stimulus control and depression of diazepam were antagonized by yohimbine. Yohimbine (1.0 mg/kg) also significantly shifted the dose-effect curve of diazepam cue to the right. Bicuculline (3 mg/kg) completely antagonized the rate-decreasing effect of diazepam (1 mg/kg), but significantly potentiated the rate-suppressant effect of clonidine (10 μg/kg). These results suggest that the central noradrenaline (NA) system may be involved not only in the antianxiety, but also the sadative action of BZD. The nature of NA involvement in relation to the different subtypes of BZD receptors requires further exploration.
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  • 94
    ISSN: 1432-2072
    Keywords: Anxiety ; Depression ; Novelty-suppressed feeding ; Diazepam ; Adinazolam ; Desipramine ; Amitriptyline ; Ro15-1788 ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We have examined the anxiolytic activity of acute and chronic antidepressant treatment in an animal model of anxiety involving novelty-suppressed feeding. Rats were food deprived for 48 h, placed into a novel environment containing food, and the latency to begin eating was recorded. Chronic (21 days), but not acute injections of desipramine (DMI; 10 mg/kg) and amitriptyline (AMI; 10 mg/kg) significantly reduced the latency to begin eating compared to controls, but the percentage decrease was not as great as that seen with either acute or chronic treatment with diazepam (2 mg/kg) or adinazolam (20 mg/kg). A time course study indicated that at least 2 weeks of treatment was necessary to observe a significant anxiolytic effect of antidepressants. The anxiolytic effect of the antidepressants was specific to the novel environment, as 2 weeks of treatment with either diazepam or DMI did not influence the latency to begin eating in the home cage. Finally, a single dose of the central benzodiazepine receptor antagonist, Ro15-1788 (20 mg/kg), given 15 min prior to testing, did not block the anxiolytic effects of chronic DMI, while it completely eliminated the effect of chronic diazepam treatment. These data suggest that antidepressants acquire anxiolytic properties following chronic administration and that this effect appears to be independent of the benzodiazepine receptor system.
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  • 95
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    Psychopharmacology 95 (1988), S. 413-417 
    ISSN: 1432-2072
    Keywords: DRL-schedule ; Imipramine ; Mianserin ; Idazoxan ; Yohimbine ; Amphetamine ; α2-Adrenoceptors ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Previous studies have reported that antidepressant drugs exert specific effects on responding maintained by DRL schedules of reinforcement, giving rise to increased frequencies of reinforcement. In order to investigate whether the α2-adrenoceptor antagonist idazoxan would produce similar effects, the actions of this compound were compared with those of yohimbine, imipramine, mianserin and d-amphetamine in rats trained to lever press for food reinforcement on a DRL 60-s schedule. Neither imipramine nor mianserin produced any effects on response rate or reinforcement frequency, except at the highest doses. In contrast, both idazoxan and yohimbine gave rise to dose-related increases in rates of responding and consequent decreases in reinforcement frequencies. Amphetamine also increased responding, but higher doses of this drug produced marked hyperactivity and stereotyped movements which were not observed after idazoxan and yohimbine. Although the present behavioural baseline was not sensitive to antidepressants, it demonstrated an unexpected activity of two α2-adrenoceptor antagonists which deserves further investigation.
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  • 96
    ISSN: 1432-2072
    Keywords: Anhedonia ; Drive ; Extinction ; Free feeding ; Neuroleptic ; Pimozide ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Both pimozide pretreatment and free feeding caused within-session and between-session decrements in variable interval operant performance; response decrements generated under pimozide were maintained on transfer to free feeding, and vice versa. On subsequently testing under extinction conditions (after food deprivation and drug free) large initial increases in responding were seen in all groups, and subsequent response decrements in extinction were steeper than in either pimozide or free feeding conditions. The effects of pimozide pretreatment do not resemble those of extinction, but may in some circumstances be functionally equivalent to a decrease in drive level.
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  • 97
    ISSN: 1432-2072
    Keywords: Nucleus accumbens ; d-Amphetamine activity ; Exploration ; Raclopride ; D2-receptors ; Schizophrenia ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effect of the D2-antagonist raclopride was investigated in two test situations, which are presumed to involve dopamine (DA) transmission within the nucleus accumbens of the rat. Local injection of d-amphetamine sulphate (10 μg/0.5 μl) produced a marked increase in motor activity, measured as motility, locomotion, and rearing, which was dose- and time-dependently antagonised by local injection of raclopride (0.05–5.0 μg/0.5 μl). After an initial decrease, at low doses (0.05–0.25 μg/0.5 μl) an apparent enhancement of the d-amphetamine-induced motor activity appeared, which was most clearly seen with rearing. These lower doses, however, did not induce any clear changes in the exploratory activity in a novel environment (i.e., the second test situation). Only the higher doses used (1.0–5.0 μg/0.5 μl) decreased exploratory activity during the first 5–10 min, also measured as motility, locomotion, and rearing. These data are discussed with respect to the role of D2-receptors within the nucleus accumbens of rats in the motor activity induced by a novel environment and d-amphetamine. Overall, the data underline previous notions that raclopride is a potent antagonist of DA-mediated behaviour.
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  • 98
    ISSN: 1432-2072
    Keywords: Haloperidol ; Partial reinforcement ; Continuous reinforcement ; Extinction ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of haloperidol 0.1 mg/kg on the partial reinforcement extinction effect (PREE) paradigm at one trial a day, were examined. Two groups of rats were trained to run in a straight alley. The continuously reinforced (CRF) group received food reward on every trial. The partially reinforced (PRF) group was rewarded on a quasirandom 50% schedule. All animals were then tested in extinction. Haloperidol 0.1 mg/kg was administered in a 2 × 2 design, i.e., drug-no drug in acquisition and drug-no drug in extinction. The PREE, i.e., increased resistance to extinction of partially reinforced as compared to continuously reinforced animals, was obtained in all four drug conditions. The administration of haloperidol in acquisition increased markedly resistance to extinction in CRF animals. The administration of the drug in extinction decreased resistance to extinction in both CRF and PRF animals. The results are explained in terms of two independent actions of haloperidol: the well-known effect of reduction in the effectiveness of reinforcement as well as enhancement of the effectiveness of nonreinforcement.
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  • 99
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    Psychopharmacology 95 (1988), S. 553-555 
    ISSN: 1432-2072
    Keywords: Drug discrimination ; Physostigmine ; M1 receptors ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rats were trained to discriminate 0.10 mg/kg SC physostigmine from saline in a two-lever food-reinforced task. There was generalization to the acetylcholine esterase inhibitor THA as well as to the muscarinic receptor agonists arecoline, oxotremorine and RS 86, but not to neostigmine or nicotine. The physostigmine cue was blocked by SC scopolamine hydrobromide and by ICV pirenzepine, but not by scopolamine methylbromide or by mecamylamine. These antagonism studies suggest that the discriminative cue elicited by physostigmine might be mainly mediated by central M1 receptors.
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  • 100
    ISSN: 1432-2072
    Keywords: 5-HT1A receptors ; 5-HT1B receptors ; 5-HT1C receptors ; RU24969 ; TFMPP ; Feeding ; 8-OH-DPAT ; Hypothalamus ; Paraventricular nucleus ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The 5-HT1B agonist RU24969 when given either systemically (1 mg/kg SC) or by infusion (0.5, 1.0, 2.0 μg) into the region of the paraventricular nucleus of the hypothalamus caused dose-dependent hypophagia in rats previously deprived of food for 18 h. Similar results were obtained at the above dosages of 1-[3-(trifluoromethyl) phenyl] piperazine (TFMPP), which acts on 5-HT1B and possibly also on 5-HT1C receptors. Neither drug significantly affected locomotion following central administration. Food intake was significantly decreased when the 5-HT1A agonist 8-OH-DPAT was given systemically (1 mg/kg SC) to rats previously deprived of food but was unaffected when 8-OH-DPAT (1 μg) was infused into the paraventricular nucleus of both food-deprived and free feeding rats. Therefore, hypophagia occurs when hypothalamic 5-HT1B (and possibly 5-HT1C) but not 5-HT1A receptors are activated.
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