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  • 1985-1989  (230)
  • 1975-1979
  • 1989  (230)
  • Rat  (120)
  • Immunohistochemistry  (116)
  • 1
    ISSN: 1432-2307
    Keywords: Malignant fibrous histiocytoma ; Ultrastructure ; Enzyme histochemistry ; Immunohistochemistry ; “Fibrohistiocytoid cell”
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Ultrastructural, enzyme histochemical and immunohistochemical studies were performed on tissue obtained from eight cases of malignant fibrous histiocytoma (MFH) and five cases of sacral decubitus ulcer. The MFH was composed of two major tumour cell types: fibroblast-like and histiocyte-like cells. Both cell types demonstrated abundant branching, fragmented rough endoplasmic reticulum (rER), many free ribosomes, occasional small mitochondria, an oval, elliptical or irregularly shaped nucleus with one or two prominent nucleoli and often a few dense bodies. However, pseudopodial projections, multivesicular bodies and phagosomes, common histiocyte organelles, were not seen. With little difference between cases or selection sites, the MFH cells reacted to acid phosphatase (AcP) and α-naphtyl butyrate esterase (ANBE) by enzyme histochemistry and with ferritin (Fer), α1-antitrypsin (AT), α1-antichymotrypsin (ACT), fibronectin (FN), HLA-DR, HLA-DP, Leu 10 and OKT 9 in immunohistochemical studies. MFH tumour cells did not immunostain with monocyte/macrophage markers (Leu M1, Leu M3, Mo 1, Mo 2 and Macrophage) although non-neoplastic histiocytes did react to these markers. In addition, granulation tissue, such as that found in sacral decubitus ulcers, was examined and the existence of a specific cell type called the “fibrohistiocytoid (FH) cell” was documented. The FH cell was short, spindle shaped and elliptical. Ultrastructurally, it had fragmented rER distributed in a branching pattern, dispersed free ribosomes, small mitochondria and a few dense bodies, but lacked diverse fused lysosomes and distinct pseudopodial cytoplasmic extensions. The FH cells reacted with AcP, alkaline phosphatase and ANBE but not with peroxidase using enzyme histochemistry and with Fer, AT, ACT, FN, HLA-DR, HLA-DP, Leu 10 and OKT 9 but not with monocyte/macrophage markers, C3d receptor, C3bi receptor in immunohistochemical studies. The FH cells had morphological, enzyme histochemical and immunohistochemical characteristics intermediate between fibroblasts and histiocytes. Similarities between MFH cells and the FH cells seen in chronic inflammation are discussed.
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  • 2
    ISSN: 1432-2307
    Keywords: Brain neoplasms ; Growth fraction Ki-67 ; Epidermal growth factor receptor ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 100 tumours of the human nervous system were investigated by means of immunohistochemistry in order to determine the expression of epidermal growth factor receptor (EGFr) and the proliferative activity as evaluated by demonstration of the proliferation-associated Ki-67 antigen. Epidermal growth factor receptor immunoreactivity was present in 79% (23/29) of the high-grade malignant gliomas examined but in only 9% (2/22) of the low-grade gliomas. Besides the gliomas, EGFr-expression was detectable in smaller amounts in most (13/15) meningiomas, in one anaplastic neurinoma and in individual tumour cells of one medulloblastoma. In addition, EGFr-expression was found in 50% (6/12) of metastatic carcinomas. Seven of eight medulloblastomas, two cerebral primitive neuroectodermal tumours (PNETs), three benign neurinomas, one ganglioneuroma, one metastatic intracerebral malignant melanoma, three spinal plasmocytomas and one immunocytoma showed no detectable EGFr-expression. Our results indicate that (1) the expression of EGFr in human tumours of the nervous system depends on the histological tumour type and (2) in the glioma group is related to the grade of malignancy. A close correlation between EGFrexpression and proliferative activity as evaluated by Ki-67 staining could not, however, be established.
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Virchows Archiv 414 (1989), S. 439-445 
    ISSN: 1432-2307
    Keywords: Granulosa cell tumour ; Immunohistochemistry ; Intermediate filament proteins ; Tumour markers ; Ovarian carcinoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Paraffin-embedded material of 47 ovarian tumours primarily diagnosed as granulosa cell tumours, including 2 cases of juvenile granulosa cell tumour, were studied immunohistochemically for the presence of intermediate filament proteins, epithelial membrane antigen and tumour markers. Forty-one lesions, including the 2 juvenile granulosa cell tumours, were vimentin positive, while keratin and epithelial membrane antigen expression could not be detected. Six tumours primarily diagnosed as poorly differentiated malignant granulosa cell tumours were vimentin negative, showed a mild to moderate positivity for keratin and intense positivity with the anti-epithelial membrane antigen antibody. These latter tumours were therefore classified as undifferentiated ovarian carcinomas, corresponding to their significantly poorer prognosis and shorter survival when compared with the granulosa cell tumours. Two of these six tumours were positive for carcino-embryonic antigen. Two small cell carcinomas of the ovary studied in addition expressed keratin in a proportion of tumour cells while no epithelial membrane antigen or vimentin was detectable. None of the tumours tested for alpha-fetoprotein, human chorionic gonadotrophin, human placental alkaline phosphatase and human placental lactogen, were positive. The data indicate the value of antibodies directed against intermediate filament proteins and epithelial membrane antigen to distinguish granulosa cell tumours from poorly differentiated carcinomas, a worthwhile distinction considering the much better prognosis of granulosa cell tumours.
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  • 4
    ISSN: 1432-2307
    Keywords: Le a ; Le b ; Le x ; Le y ; CA 19-9 ; CA-50 ; Chronic pancreatitis ; Pancreatic carcinoma ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The expression of the blood group antigens Le a, Le b, Le x, Le y and the carbohydrate antigens CA 19-9 and CA-50 was studied in 20 ductal pancreatic carcinomas, 24 pancreases with chronic pancreatitis and 10 normal fetal and adult pancreases. CA 19-9, CA-50 and Le a showed the strongest staining intensity, the highest percentage of labelled cells, and a membrane-bound expression pattern in epithelial cells of normal pancreas, chronic pancreatitis and well differentiated (G1) carcinoma; in moderately and poorly differentiated carcinomas (G2/3) it was predominantly cytoplasmic. The staining pattern of Le b and Le x was less clearly membrane-bound but varied with cytoplasmic and Golgi-located distributions in all pancreatic specimens. Le y revealed a consistent granular antigen expression in the Golgi-region of ductal epithelial, acinar and carcinoma cells. None of the antibodies allowed a morphological differentiation by their expression pattern between hyperplastic, metaplastic and dysplastic or neoplastic cells. The differences in their staining patterns were quantitative and did not allow a qualitative differentiation between chronic pancreatitis and pancreatic carcinoma. We found coexpression of Le a and Le b antigens in 46/54 pancreatic specimens. All but 7 pancreata were CA 19-9 positive. An association between Le x, y and Le a, b antigen expression could not be noted in our material.
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Virchows Archiv 414 (1989), S. 459-464 
    ISSN: 1432-2307
    Keywords: Sebaceous carcinoma ; Parotid gland ; Salivary gland ; Ultrastructure ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Sebaceous carcinoma of salivary gland origin is extremely rare and, because of its rarity, the clinicopathological characteristics and the histogenesis are not fully understood. We present a case of sebaceous carcinoma of the parotid gland which brings the total number of reported cases to 22. The tumor showed epithelial cell nests which were mainly composed of sebaceous cells with marked cellular atypia. In most of the nests, glandular spaces lined by ductal epithelium were present. Scattered mucous cells and flattened eosinophilic cells at the periphery of the nests were also seen. Ultrastructural and immunohistochemical observations of the tumour revealed coexistence of sebaceous and glandular differentiations in some tumour cells. Tumour cells with lipid granules often participated in the formation of glandular structures or exhibited intracytoplasmic lumina, and immunohistochemical localization of lactoferrin and secretory component, the functional markers of ductal epithelium of salivary gland, was demonstrated not only in duct-forming tumour cells but also in many sebaceous tumour cells. It seems likely that sebaceous carcinoma originates from pluripotential duct cells which can differentiate into sebaceous, ductal and mucous cells.
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  • 6
    ISSN: 1432-2307
    Keywords: Duodenal tubulo-villous adenoma ; Adenocarcinoma ; Immunohistochemistry ; Diameter of adenoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Primary duodenal carcinoma and duodenal adenoma are rare tumours. Duodenal carcinoma makes up about 0.3% of all malignant tumours of the gastrointestinal tract (Alwmark et al. 1980; Spira et al. 1977). The present paper describes a duodenal carcinoma arising in a mixed tubulo-villous non-Vaterian adenoma in a 68 year old male. Immunocytochemical analysis revealed evidence of neuroendocrine differentiation in both adenoma and carcinoma. In a review of the literature a correlation between the size of adenoma and the probability of concomitant carcinoma is demonstrated. Duodenal adenoma measuring more than 4 cm in diameter should be considered potentially malignant.
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  • 7
    ISSN: 1432-2307
    Keywords: MHC class II antigens ; Antigen presenting cells ; Pulmonary fibrosis ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Major histocompatibility complex (MHC) class II antigens are essential in the presentation of antigens to T lymphocytes, and cells expressing MHC class II antigens are known to play a role as antigen presenting cells (APC). We investigated the distribution of MHC class II antigens and the reactivity of monoclonal antibodies OKM1 and OKM5 in normal and fibrotic lungs immunohistochemically. The results showed that alveolar capillary endothelial cells (ACEnd) expressed MHC class II antigens and were reactive with OKM5 in both normal lungs and the non-thickened parts of alveolar septa of pulmonary fibrosis. However, ACEnd did not express MHC class II antigens and were not reactive with OKM5 in thickened alveolar septa of pulmonary fibrosis. Type II alveolar epithelial cells (AEp) proliferating and replacing type I AEp in pulmonary fibrosis expressed MHC class II antigens strongly. Alveolar macrophages expressed MHC class II antigens strongly and reacted with OKM1 in pulmonary fibrosis, especially in alveolar spaces. These findings suggest that the phenotypic changes of ACEnd may be involved in the process of pulmonary fibrosis, and type II AEp and alveolar macrophages in the parts of thickened alveolar septa may play a role as APC.
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  • 8
    ISSN: 1432-2307
    Keywords: Ageing lung ; Extracellular matrix components ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The modifications of the extracellular matrix (ExM) components in the alveolar parenchyma of elderly subjects were investigated using a panel of polyclonal antibodies. The elastic fibers showed a notable decrease along the alveolar walls while type III collagen increased when compared with that of non-elderly controls. No variations of these components were detectable in the alveolar ducts or in the respiratory bronchioli. An increase in the thickness of the alveolar basement membranes was detected in some of the subjects when antibodies against type IV collagen and laminin were used, while antibodies to fibronectin and type V collagen did not reveal any modifications compared with the controls. The modifications revealed in the lungs of the elderly can be related to the alterations of the elastic recoil and pulmonary compliance observed in these subjects.
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Virchows Archiv 415 (1989), S. 429-436 
    ISSN: 1432-2307
    Keywords: Hodgkin's disease ; Immunohistochemistry ; Microenvironment ; Spleen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Hodgkin's disease in the spleen - with the exception of its B cell variant - behaves quite differently from non Hodgkin's lymphomas with respect to both its spread and microenvironment. Each type of HD appears to create its own microenvironment by the secretion of cytokines responsible for the characteristic cellular composition of the infiltrates and thereby alters the normal immunoarchitecture of the spleen profoundly. While some histological findings seem to imply the presence of a host response against HD especially in the nodular sclerosis subtype, morphological and immunohistochemical evidence in the spleen cannot conclusively substantiate this hypothesis.
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  • 10
    ISSN: 1432-2307
    Keywords: MAM-3 and MAM-6 Antigens ; Human salivary gland tumour ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary MAM-3 and MAM-6 antigens of human milk fat globule membrane were detected immunohistochemically in 93 cases of salivary gland tumours as well as in normal glands. The antigens were visualized in 10% formalin-fixed paraffin sections. MAM-3 (MoAbs 115G3, 67D11) antigen was distributed in intercalated and striated duct cells of the normal salivary glands, and in luminal tumour cells and squamous metaplastic cells of pleomorphic adenomas. In pleomorphic adenomas the frequency of positive staining with MoAb 67D11 (54/67; 80.6%) was higher than that with MoAb 115G3 (36/67; 53.7%). MAM-6 (MoAbs 115D8, 115F5) antigen was expressed in luminal and lateral borders of serous acinar cells and ductal of the normal glands, and also in luminal borders of tubulo-ductal and glandular structures of salivary gland tumours. Ductal basal cells were characterized by existence of positive staining for MAM-6 antigen, in adenolymphomas MAM-6 antigen was restricted to the basal tumour cells. Some mucous cells of mucoepidermoid tumours were stained specifically with MoAb 115G3, and epidermoid cells of mucoepidermoid carcinomas manifested MAM-6 antigen staining. Immunohistochemical localization of MAM-6 antigen resembled that of epithelial membrane antigen (EMA) detected with MoAb.
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  • 11
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 97 (1989), S. 175-178 
    ISSN: 1432-2072
    Keywords: Serotonin ; Morphine ; Nicotine ; Amphetamine ; Reward ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effect of two potent and specific antagonists of 5HT3 receptors, ICS 205-930 and MDL 72222, on the reinforcing properties of amphetamine, morphine and nicotine was studied in rats. Durg-induced reinforcement was assessed by measuring drug-conditioned place preference. ICS 205-930 and MDL 72222 dose-dependently reduced the place preference induced by morphine (1.0 mg/kg SC). At doses of 0.030 mg/kg SC the two antagonists completely blocked morphine-induced place preference while doses of 0.015 mg/kg SC significantly reduced it. ICS 205-930 and MDL 72222 at doses of 0.030 mg/kg SC also prevented the place preference induced by nicotine (0.6 mg/kg SC). In contrast, ICS 205-930 and MDL 72222 up to doses of 0.030 mg/kg SC failed to modify the place preference elicited by amphetamine (1.0 mg/kg SC). The results indicate that 5HT3 receptors are specifically involved in the reinforcing properties of morphine and nicotine.
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  • 12
    ISSN: 1432-2072
    Keywords: Hallucinogenics ; Amphetamine ; Rat ; Tele-Stereo-EEG
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Telemetric recordings of field potentials from frontal cortex, hippocampus, striatum and reticular formation of freely moving rats were analysed before and after injection of the enantiomeric hallucinogenic amphetamine derivatives R-DOB [(−)-1-(2,5-dimethoxy-4-bromophenyl)-2-aminopropane], R-DOM [(−)-1-(2,5-dimethoxy-4-methylphenyl)-2-amino-propane] and R-DOI [(−)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropanel] as well as the nonhallucinogenic amphetamine derivatives S-MBDB [(+)-N-methyl-1-(1,3-benzodioxol-5-yl)butanamine] and S-MDMA [(+)-3,4-methylenedioxymethamphetamine] and S-(+)-amphetamine. The frequency analysis of the field potentials revealed a clearcut difference between them. The spectral patterns emerging after injection of the non-hallucinogens were characterized by a general decrease of power, the changes in the alpha2 and delta band being the most prominent, whereas only after the application of the hallucinogenic compounds was a contrasting increase of power observed in the alpha1 frequency band, especially in the striatum. As increases in alpha1 power have been correlated in the same pharmacological model to serotonergic control mechanisms, the results are in line with the hypothesis that 5-HT2 receptors, predominantly occurring in the striatum, might be involved in the hallucinogenic action of drugs.
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  • 13
    ISSN: 1432-2072
    Keywords: Haloperidol ; Dopamine ; Oral movements ; Rat ; Tardive dyskinesia ; Homovanillic acid
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rats with more severe orofacial movements after 51 days of haloperidol administration showed lower levels of the dopamine metabolite homovanillic acid (HVA) in the caudate compared to animals who did not develop significant mouth movements. This effect was not observed in other brain regions sampled. This finding is consistent with the hypothesis that dopaminergic receptor supersensitivity in neostriatal structures plays some role in the development of orofacial movements in rats, in association with chronic neuroleptic administration.
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  • 14
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 99 (1989), S. 140-142 
    ISSN: 1432-2072
    Keywords: γ2-MSH ; Naloxone ; Opiate dependence ; Taste preference conditioning ; Taste aversion ; Withdrawal motivation ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A two flavour, unbiased, taste preference conditioning procedure was used to test for possible motivating effects of γ2-MSH. Three training trials failed to produce any significant effect with doses ranging from 2.4 to 40 μg/ ICV infusion in drug-naive, non-operated or placebo-implanted rats. However, in rats made dependent by SC implantation of a morphine pellet 4 days earlier 15 μg γ2-MSH/infusion produced a taste aversion that was comparable to that produced by infusion of a low dose of the competitive opioid receptor antagonist naloxone (0.32 μg). The findings confirm with a conditioning procedure and with opiate-dependent animals the naloxone-like effects of γ2-MSH. They also suggest that this endogenously-located peptide may acquire an aversive property as a result of chronic morphine treatment.
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  • 15
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 99 (1989), S. 352-356 
    ISSN: 1432-2072
    Keywords: Conditioned locomotion ; MDMA ; Aniphetamine ; Cocaine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Daily administration of a drug in a distinctive environment establishes contingencies that support Pavlovian conditioning. Environmental cues that are paired with the drug injection and that predict the onset of drug action can become conditioned stimuli. Ultimately, the conditioned stimuli come to predict the availability of drug and develop the potential to engender conditioned drug responses. Various psychostimulant drugs can produce conditioned locotnotion when tested in the presence of environmental cues that were repeatedly associated with the drug experience. The ability of amphetamine and cocaine to produce conditioned locomotion was demonstrated in the present study. Stimulant-like properties of methylenedioxymethamphetamine (MDMA) have been reported in locomotor paradigms, drug discrimination procedures, and human subjective questionnaires. MDMA (5 mg/kg), paired for 5 days to a distinct environment signalled by the presence of a distinct odor, produced enhanced locomotion during a test probe with the odor alone indicating that MDMA can also produce conditioned locomotion. The observation that the stimulus properties of MDMA can also become associated with environmental cues supports the hypothesis that some of the behavioral effects of MDMA resemble those of other classical psychostimulants such as amphetamine and cocaine.
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  • 16
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 99 (1989), S. 366-370 
    ISSN: 1432-2072
    Keywords: Ethanol tolerance ; Intoxicated practice ; Motor impairment ; Hypothermia ; Narcosis ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The development of tolerance to the motor impairment effect of ethanol was examined in separate groups of rats receiving and not receiving intoxicated practice. Tolerance to the motor impairment effect of ethanol developed whether or not rats received intoxicated practice during chronic ethanol treatment. Depending on the treatment dosage and test dose, intoxicated practice might enhance the level of tolerance attained. Tolerance to other effects of ethanol (hypothermia and narcosis) developed as a function of the treatment dosage. Intoxicated practice on the moving belt did not modify the development of tolerance to these effects of ethanol. Tolerance to the motor impairment effect of ethanol, however, was retained much longer in the intoxicated practice group following the termination of ethanol treatment.
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  • 17
    ISSN: 1432-2072
    Keywords: Thermoregulation ; Acetylcholine ; Muscarinic ; Serotonin ; Interaction ; Alaproclate ; Oxotremorine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Stimulation of muscarinic cholinergic receptors with the highly potent and selective receptor agonist oxotremorine produced hypothermia in rats. Alaproclate, a purported selective serotonergic reuptake inhibitor, potentiated this response. Destruction of central presynaptic serotonergic terminals with the potent cytotoxin p-chloroamphetamine (PCA) failed to attenuate the hypothermic response to oxotremorine in alaproclate-pretreated animals. These results could be taken to suggest that alaproclate may act, at least in part, via a non-serotonergic mechanism to potentiate the oxotremorine-induced hypothermic response.
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  • 18
    ISSN: 1432-2072
    Keywords: Penile erection ; Yawning ; Hypophysectomy ; Monosodium glutamate ; Oxytocin ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Penile erection and yawning induced by the intracerebroventricular (ICV) injection of oxytocin (10–1000 ng) was studied in hypophysectomized rats and in rats neonatally treated with monosodium glutamate (MSG), a treatment that depletes hypothalamic opiomelanocorticotropinderived peptides without altering their pituitary and circulating concentration. Oxytocin effect was strongly reduced by hypophysectomy, but not by neonatal MSG. Testosterone replacement (50 μ/kg/day for 23 days) partially reversed the effect of hypophysectomy on penile erection, but not on yawning. The present results suggest that oxytocin does not induce penile erection and yawning by releasing an ACTH-derived peptide from hypothalamic opiomelanotropinergic neurons, and that the pituitary gland exerts a permissive role on the expression of the above behavioural responses induced by oxytocin.
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  • 19
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 97 (1989), S. 466-470 
    ISSN: 1432-2072
    Keywords: Drug discrimination ; Benzodiazepine ; Midazolam ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rats (N=12) were trained to discriminate midazolam (1 mg/kg, IP) from vehicle in a food reinforced operant conditioning procedure. Midazolam, flunitrazepam, diazepam, chlordiazepoxide and pentobarbital showed dose-dependent substitution for midazolam. Buspirone and Ro 15-1788 did not substitute for midazolam. The midazolam cue was dose-dependently antagonized by Ro 15-1788. In rats (N=12) trained to discriminate chlordiazepoxide (3 mg/kg, IP) from vehicle midazolam, flunitrazepam, diazepam and chlordiazepoxide substituted completely and dose dependently for chlordiazepoxide. The relative potency of chlordiazepoxide and diazepam was three times less in the midazolam-trained animals than in the chlordiazepoxide-trained animals. Response rate and latency data further support the main finding that the midazolam cue is similar, but not identical to the cue of classical benzodiazepines.
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  • 20
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 98 (1989), S. 203-206 
    ISSN: 1432-2072
    Keywords: Place conditioning ; Motivation ; Aversion ; Opioids, μ-, δ- and κ-receptors ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The role of central versus peripheral opioid receptors in mediating the aversive effects of opioids was examined by use of an unbiased place preference conditioning procedure in rats. The non-selective opioid antagonist naloxone (NLX) produced conditioned aversions for the drug-associated place after subcutaneous (SC) as well as intracerebroventricular (ICV) administration. Place aversions were also observed in response to the ICV administration of the selective μ-antagonist CTOP. In contrast, the selective δ-antagonist ICI 174,864 and the selective κ-antagonist norbinaltorphimine (nor-BNI) (ICV) were without effect. Place aversions were also produced by central applications of the selective κ-agonist U50,488H and the dynorphin derivative E-2078. For those opioid ligands tested, the doses required to produce place aversions were substantially lower following ICV as compared to SC administration. These data confirm that κ-agonists and opioid antagonists produce aversive states in the drug-naive animal and demonstrate that this effect is centrally mediated. Furthermore, the ability of NLX and CTOP, in contrast to both ICI 174,864 and nor-BNI, to produce place aversions suggests that the aversive effects of opioid antagonists result from the blockade of μ-receptors.
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  • 21
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 98 (1989), S. 530-534 
    ISSN: 1432-2072
    Keywords: Morphine ; Opiates ; Dependence ; Nucleus accumbens ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Previous studies from our laboratory using methylnaloxonium, a hydrophilic antagonist, showed that opiate receptors in the region of the nucleus accumbens are important for the acute reinforcing effects of heroin in non-dependent rats. A similar increased sensitivity to the response disruptive effects of intracerebrally injected methylnaloxonium in opiate dependent rats was observed in a fixed-ratio (FR) baseline of operant behaviors. These results suggest that the same opiate receptors in the region of the nucleus accumbens important for the positive reinforcing stimulus properties of opiates may also be responsible for the response disruptive, aversive stimulus properties of opiate withdrawal. These results also suggest that the neural substrates of some aspects of dependence may be partly related to those of the reinforcing effects of opiates. In particular, it is hypothesized that “euphoria” and “dysphoria” induced by opiates may reflect opponent motivational processes operating at a cellular level within the nucleus accumbens.
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  • 22
    ISSN: 1432-2072
    Keywords: Cocaine ; Dopamine ; Dopamine receptors ; Drug discrimination ; Drug stimuli ; Receptors ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The involvement of dopamine (DA) receptor subtypes in the behavioral effects of CNS stimulants was studied in rats trained to discriminate occaine from saline. In substitution tests, the stimulus effects of 10mg/kg of this substance generalized tod-amphetamine (0.25–1.0 mg/kg) and the selective D2 against LY-171555 (0.05–0.25 mg/kg); but not to the D1 agonist SKF-38393 (5.0–15.0 mg/kg); in combination tests, the D1 antagonist Sch-23390 (0.0625–0.5 mg/kg) significantly blocked, and the D2 antagonist spiperone (0.25–0.5 mg/kg) partially blocked the cocaine cue. These data suggest that the involvement of DA systems in the behavioral effects of cocaine is more complex than either D1 or D2 receptor activation; for example, the stimulus properties of this substance might involve both D1 and D2 receptor activation.
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  • 23
    ISSN: 1432-2072
    Keywords: Riluzole ; FG 7142 ; β-Carboline ; Anxiety ; Conflict procedures ; Animal model ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The possible anxiolytic activity of riluzole, a drug which interferes with glutamic acid neurotransmission, was studied in rats using operant conflict procedures. In both “anxiolytic” and “anxiogenic” procedures, riluzole alone did not possess any anticonflict or proconflict effect at doses of 2 and 4 mg/kg PO. Riluzole over the same dose-range was able to antagonize the well known proconflict effect of the β-carboline derivative FG 7142, an inverse agonist at the GABA-benzodiazepine-chloride ionophore receptor complex. This effect could be related to the possible interaction of riluzole with glutamic acid neurotransmission, since it has been demonstrated previously that β-carbolines such as DMCM and β-CCM were able to deplete the levels of aspartic and glutamic acids in rodent cortex, perhaps by enhancing release of amino acid neurotransmitters. If one subscribes to the hypothesis that the anxiety induced by β-carboline derivatives is related to depression, riluzole might be of value in the treatment of anxiety related to depression.
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  • 24
    ISSN: 1432-2072
    Keywords: LY 163502 ; Dopamine D-1 and D-2 receptors ; Jerking ; Behavioural assessment ; Stereotypy ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The new, extremely potent and enantioselective D-2 agonist LY 163502 failed to induce compulsive stereotyped behaviour. Very low doses (3–6 μg/kg) inhibited spontaneous sniffing and locomotion, while higher doses (12–50 μg/kg) induced episodes of non-stereotyped sniffing and chewing; these actions showed complete enantioselectivity. Up to 200-fold higher doses modestly induced only locomotion. Responsivity to LY 163502 was enantioselectively blocked by the selective D-2 antagonist R-piquindone. This responsivity was also enantioselectively blocked by the selective D-1 antagonist R-SK&F 83566 but, additionally, episodes of atypical limb/body jerking behaviour were released; thus, LY 163502 induced such jerking only when tonic D-1 activity was suppressed. These data extend our notion that there may be at least two forms of functional interaction between D-1 and D-2 receptor systems: one cooperative, as in the regulation of typical sniffing, and another oppositional, as in the regulation of atypical jerking.
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  • 25
    ISSN: 1432-2072
    Keywords: SCH 23390 ; Catalepsy ; Tolerance ; Neuroleptics ; Rat ; Chronic treatment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The development of tolerance to the cataleptic effect of the selective D-1 antagonist SCH 23390 (0.5 mg/kg/day SC or 0.1 mg/kg/day SC) and haloperidol (1 mg/kg/day SC) during repeated administration was investigated. Catalepsy in rats was measured using the horizontal bar method. SCH 23390 induced a dose-related cataleptic effect of short duration, whereas the cataleptic effect of haloperidol appeared more slowly and lasted longer. Marked tolerance to the cataleptic effect of haloperidol developed already 6 days from the beginning of the treatment. The cataleptic effect of the higher dose regimen of SCH 23390 was also significantly reduced after 6 days' treatment. However, unlike haloperidol, this subacute tolerance was gradually reversed and was no longer significant after 12 and 18 days. The cataleptic response to the lower dose of SCH 23390 (0.1 mg/kg/day) was not significantly altered during the treatment and no initial catalepsy tolerance was observed with this dose regimen. These results suggest that different mechanisms are involved in the expression of cataleptic behaviour during chronic treatment with SCH 23390 and classical antipsychotics, such as haloperidol.
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  • 26
    ISSN: 1432-2072
    Keywords: Social memory ; Cholinomimetic drugs ; Nootropic drugs ; Benzodiazepine inverse agonists ; Psychostimulants ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The recognition of an unfamiliar juvenile rat by an adult rat has been shown to imply short-term memory processes. In this study the effect of various psychotropic drugs on this investigatory behaviour was examined. The procedure was as follows: an unfamiliar juvenile rat was placed in the home cage of an adult rat for 5 min. The time spent by the adult rat in investigating the juvenile was recorded. The adult rat was then immediately treated with vehicle or test compounds, and was again exposed for 5 min to the same juvenile 2 h later. At this time point vehicle-treated rats no longer recognized the juvenile rat, i.e. the time of investigation was similar to that observed during the first presentation. Arecoline (1 and 3 mg/kg IP), physostigmine (0.05 and 0.1 mg/kg SC), RS86 (0.5 mg/IP) and nicotine (0.125 and 0.5 mg/kg IP) reduced in a dose-dependent fashion the time spent in investigating the juvenile during the second exposure. This result cannot be attributed to nonspecific effects, since it was not observed when a different juvenile was used for the second exposure. The effect of arecoline was reversed by scopolamine, but not by methylscopolamine. Aniracetam reduced investigatory behaviour at the dose of 50 mg/kg IP. FG 7142 (5 mg/kg IP) and β-CCM (0.4 mg/kg IP) were also active and their effect was reversed by Ro 15-1788. dl-Amphetamine (0.5 and 1 mg/kg IP), nomifensine (1.25–10 mg/kg IP) and strychnine (0.25 and 0.5 mg/kg IP) were ineffective or reduced this behaviour unspecifically. Social recognition may therefore represent a useful and simple test to detect compounds which enhance short-term, olfactory, memory and to assess in the same animals the specificity of this activity.
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  • 27
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    Psychopharmacology 98 (1989), S. 286-288 
    ISSN: 1432-2072
    Keywords: IP pirenzepine ; Passive avoidance ; Brain penetration ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract When injected IP, the M1 muscarinic receptor antagonist pirenzepine dose-dependently induced a deficit in passive avoidance learning in rats. This activity was optimal at 75 mg/kg injected 1 h before the acquisition session. The deficit induced by pirenzepine was antagonized by oxotremorine (0.03–0.3 mg/kg SC) and physostigmine (0.1 mg/kg SC), but not neostigmine. By comparison, under the same experimental conditions, physostigmine and oxotremorine also antagonized the deficit induced by an equipotent dose of scopolamine (0.5 mg/kg IP), although the activity of physostigmine appeared stronger against scopolamine than against pirenzepine. These results suggest that pirenzepine could produce a centrally-mediated behavioural disruption when injected systemically.
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  • 28
    Electronic Resource
    Electronic Resource
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    Psychopharmacology 98 (1989), S. 412-416 
    ISSN: 1432-2072
    Keywords: Adrenoceptors ; Behaviour ; Noradrenaline ; Open field ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rats were injected IP once daily for 14 consecutive days with propranolol (5 mg/kg), yohimbine (2.5 mg/kg) or saline vehicle. A fourth group was unhandled during this time. Each rat was then placed in an open field for 4 min and its activity and defaecation recorded. Immediately after this, the animals were killed and cerebral cortices removed for radioligand binding to α2- and β-adrenoceptors and measurement of noradrenaline content. We report two sets of findings. First, β-adrenoceptor density correlated positively, and affinity negatively, with the number of movements towards the centre of the field in the final 3 min of the trial. α2-Adrenoceptor K d, in contrast, correlated both with movements around the field and those directed towards the centre. Secondly, whereas the only specific drug effect was an increase in defaecation after treatment with propranolol, β-adrenoceptor density was increased and affinity decreased in all injected groups, suggesting a non-specific effect of the stress of injection. Movements to and from the centre of the field were also increased in injected groups during the first minute of the trial. In both sets of findings the association of β-adrenoceptor density with greater resistance to stress is hard to reconcile with existing theories of the role of β-adrenoceptors in behavioural responses to stress.
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  • 29
    ISSN: 1432-2072
    Keywords: Neuropeptide Y ; Anxiolysis ; Conflict model ; Alpha-adrenergic ; Idazoxan ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Effects of intracerebroventircular (ICV), neuropeptide Y (NPY) (0.2–5.0 nmol) and its C-terminal 13–36 amino acid (AA) fragment (0.4–2.0 nmol) have been examined with respect to anxiolytic properties in two rat anxiety models, Montgomery's conflict test (MT), and Vogel's drinking conflict test (VT). In the MT, 1.0 and 5.0 nmol NPY abolished the normal preference for the closed arms of the maze. At 5.0 nmol, the total number of entries made into both closed and open arms was decreased by 50%. In the VT, both 0.2 and 1.0 nmol NPY markedly increased the number of shocks accepted. The effect of 5.0 nmol NPY was less pronounced. In control experiments, NPY (0.2 nmol) did not affect pain sensitivity or thirst. Pretreatment with the selective alpha2-adrenergic receptor antagonist idazoxan, at a dose which by itself did not affect behaviour (2.0 mg/kg), antagonized the effect of 1.0 nmol NPY in the VT. NPY 13-36 was without significant effect in both models. The results suggest that NPY exerts anxiolytic-like effects, and that these effects are mediated through an interaction with noradrenergic systems. Higher doses of NPY produce sedation and ataxia, which decrease overall activity in the MT, and interfere with the ability fully to express behaviourally the anxiolytic-like effect in the VT. The findings are discussed in relation to the noradrenaline hypothesis of anxiety, and to observations indicating involvement of NPY in the pathophysiology of major depression.
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  • 30
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    Pflügers Archiv 413 (1989), S. 217-224 
    ISSN: 1432-2013
    Keywords: Rat ; Kidney ; Uptake ; Transport ; α-Ketoglutarate ; Luminal ; Basolateral ; Production
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In order to establish the characteristics of net renal transport and utilization of α-ketoglutarate (α-KG) in the rat, we have precisely quantified the renal blood flow, the urinary flow and the rates of α-KG delivery, filtration, reabsorption or secretion, excretion, uptake or production by an in vivo rat kidney preparation. In normal rats, α-KG uptake was higher than α-KG reabsorption at both endogenous and elevated plasma α-KG concentrations; thus, a net peritubular transport, which was the main supplier of α-KG to the renal cells, took place. Saturation of reabsorption and peritubular transport of α-KG occurred at blood α-KG concentrations about 30 and 150 times above normal, respectively. Acute metabolic acidosis was found to have no effect on renal handling of α-KG. At endogenous plasma α-KG concentrations, alkalosis converted net renal uptake into net renal production of α-KG resulting in addition of α-KG by the renal cells both to blood and to the luminal fluid. Elevation of blood α-KG concentration restored the renal uptake of α-KG. This uptake, which was entirely accounted for by the peritubular transport of α-KG, reached a maximum which was lower than that observed in normal and acidotic rats.
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  • 31
    ISSN: 1432-2013
    Keywords: Fast-twitch muscle ; Chronic stimulation ; Contractil properties ; Parvalbumin ; Sarcoplasmic reticulum ; Ca2+-uptake ; Rat ; Rabbit
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This study compares changes in contractile properties, Parvalbumin content, and Ca2+-uptake by the sarcoplasmic reticulum (SR) of low-frequency stimulated rat and rabbit tibialis anterior (TA) muscles. Time to peak tension increased 1.8-fold in 35-day stimulated rabbit TA, while no change occurred in rat TA. Isometric twitch tension increased 2-fold in rabbit TA, but was unaltered in rat TA. Parvalbumin (PA) content was more than 90% reduced in rabbit TA, but only 60% in rat TA after 35 days. At this time, PA content of the stimulated rat TA was still higher than that of normal rabbit TA. Taking into account the suggested role of PA as a cytosolic Ca2+ buffer, its decrease could lead to an impaired free Ca2+-decay with a prolonged active state and a higher tension output during a single twitch. This would explain why chronic stimulation led to an increase in isometric twitch tension in rabbit TA, but not in rat TA. The 1.6-fold rise in half-relaxation time of 35-day stimulated rat and rabbit TA most likely resulted from a 50% reduced Ca2+-uptake by the SR, due to a still unknown modification of the Ca2+-transport ATPase.
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  • 32
    ISSN: 1432-2013
    Keywords: Rat ; Skeletal muscle ; Development ; Ionic conductances ; Denervation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The development of membrane ionic conductances of rat extensor digitorum longus (EDL) muscle fibers was studiedin vitro using intracellular recordings. At 7–8 days after birth, the potassium conductance (GK) dominated the total membrane conductance while the chloride conductance (GC1) was very low. A rapid increased of GC1 towards adult values was observed after few days (12–14 day old rats), whereas GK did not decrease up to day 23. Denervation at 7–8 days after birth suppressed the maturation of the electrical parameters measured, and 15 days after the nerve crush, GC1 was just detectable. These results suggest that the maturation of the electrical properties, and in particular that of the resting chloride conductance in mammalian striated muscle fibers, occurs during the first weeks of postnatal life and is dependent on innervation.
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  • 33
    ISSN: 1432-2013
    Keywords: Amiloride ; Bumetanide ; Cl-secretion ; Electrical field stimulation ; Large intestine ; Na-absorption ; Rat ; Stripping ; Submucosal plexus ; Tetrodotoxin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The initial phase of in vitro experiments in Ussing-type chambers on large intestine is characterized by short-circuit currents (ISC) declining from high starting values to a lower plateau within 0.5 h. The origin of this “initial ISC-transient” was investigated by ISC measurements on partially stripped segments of rat rectal colon. Transport was pre-stimulated in vivo by keeping animals in barbiturateanesthesia for 5 h prior to tissue preparation. This procedure caused by endogenous aldosterone-liberation amiloride-sensitive Na-absorption to become the predominant electrogenic transport. The initial ISC-transient was abolished by tetrodotoxin (TTX, 1 μM), indicating a neuronal mediation of this phenomenon. In order to identify the transport which was subject to neuronal control, the amiloride-sensitive Na-absorption was measured during electrical field stimulation (bipolar rectangular pulses: 5 Hz, 1 ms, ±6 mA). There was no difference to unstimulated controls. In contrast, the initial ISC-transient was dependent on Cl in the bath following Michaelis-Menten-kinetics (K M=20 mM) and could be prevented by 10 μM serosal bumetanide. Then, initial filling of the Ussing-chamber was imitated during the course of the experiment by removal and immediate readdition of the bathing fluid. This procedure caused ISC-changes of similar appearance as the initial ISC-transient. To verify that indeed mechanical stretch is the sensory stimulus triggering the initial ISC-transient, the effect of small pressure oscillations was studied. This also produced an ISC-transient which was TTX-sensitive and was abolished after removal of the submucosal plexus Meissner by total stripping. It is concluded that amiloride-sensitive Na-absorption does not contribute to the initial transient and is not affected by the enteric nervous system. Initial ISC-transients asobserved during the first half hour of Ussing experiments are due to electrogenic Cl-secretion which is stimulated by mechanical stretch during tissue preparation and filling of the chamber via a submucosal neuronal reflex pathway. The possible biological meaning of this stretch-induced secretory process could be facilitation of transit during imminent stasis of the gut contents.
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  • 34
    ISSN: 1432-2307
    Keywords: Lymphatics ; Factor VIII-related antigen ; Ulex europaeus 1 lectin ; Laminin ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In order to investigate the antigen profile in human lymphatic vessels when compared with blood vessels, postmortem retrograde lymphangiography was done via the thoracic duct on six patients. Formalin fixed, paraffin embedded tissue was stained immunohistochemically for Factor VIII-Related antigen (F VIII R:Ag), with Ulex Europaeus 1 lectin (UEA-1) and for laminin. The results show that the endothelium of blood vessels and lymphatics at all levels of the lymphatic system react positively following staining for Factor VIII-R:Ag and with UEA-1 lectin. The staining for F VIII R:Ag was generally weaker in the endothelial cells lining lymphatic vessels. Staining for the basement membrane component laminin can be used to distinguish lymphatic capillaries and smaller lymphatic collecting vessels from blood vessels.
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  • 35
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    Virchows Archiv 414 (1989), S. 231-241 
    ISSN: 1432-2307
    Keywords: Gastric carcinoma ; Lymphoid stroma ; T lymphocytes ; HLA-DR ; Interleukin-1 ; Mucin histochemistry ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A total of 626 surgically resected gastric carcinomas were reviewed, and 24 cases (3.8%) of “gastric carcinoma with lymphoid stroma” were identified. The tumour cells were consistently arranged in an anastomosing trabecular or alveolar pattern and were densely infiltrated by lymphoid cells. The specimens were studied using mucin histochemistry and the indirect immunoperoxidase method to determine the histochemical properties of this form of gastric carcinoma. The tumour cells were consistently positive for concanavalin A paradoxical staining, class III and almost devoid of acidic mucins, features demonstrating preferential differentiation toward pyloric glands or pseudopyloric glands. Immunohistochemically, positive reactions for Leu M1 and lysozyme, marker substances of (pseudo)pyloric gland cells, were often observed. Carcinoembryonic antigen was positive in focal areas without (pseudo)pyloric glandular patterns. Secretory component was focally positive. HLA-DR was strongly expressed in most cancer cells and 17 tumours (71%) showed positivity for interleukin 1 (IL-1). The lymphoid stroma contained a high percentage of UCHL1-reactive T cells both within and around the cancer cell nests, while SL26-reactive B cells clustered in lymphoid follicles. A considerable number of T-lymphoid cells were also reactive for IL-1. A number of plasma cells with a predominance of IgG-type were distributed around the cancer cell nests. S-100 protein-positive dendritic cells were not identified. We speculate that the prominent lymphoid stroma including intraepithelial lymphocyte-like T cells with IL-1 receptors is possibly induced by IL-1 related mediators released from the HLA-DR-positive gastric cancer cells of the (pseudo)pyloric gland-type.
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  • 36
    ISSN: 1432-2307
    Keywords: Barrett's oesophagus ; Mucus ; Histochemistry ; Immunohistochemistry ; Precancerous lesion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Columnar cell lined lower oesophagus (CELLO), often considered to be a precancerous lesion, is characterized by a glandular mucosa with a predominance of sulphomucins in the specialized epithelium. This histochemical abnormality can be correlated with abnormal differentiation which may also be studied by anti-mucus antibodies (anti-M1, anti-M3, anti-SIMA, anti-LIMA). The purpose of this prospective study is to define the mucin profile in a large population of CELLO by immunohistochemistry and to compare it with the results of histochemistry. Biopsies of 79 patients with reflux oesophagitis were included. Thirty-eight had CELLO and 41 had a histologically normal cardia. Six surgical specimens of oesophageal adenocarcinomas were also included. The histochemical methods confirmed the preponderance (57.9%) of type III intestinal metaplasia (IM) found in 57.9% of cases. The immunohistochemical methods showed a similar antigenic profile of type II and III IM with positivity of anti-SIMA and anti-M3 antibodies in the goblet cells, and positivity of anti-LIMA antibodies in both the goblet and intermediate cells of the specialized epithelium. The mucus secreting cells of the oesophageal adenocarcinomas had the same immunohistochemical profile. These results are similar to those of Filipe et al. in type II and III IM surrounding gastric adenocarcinomas. Immunohistochemical methods allow us to subdivide type II and type III IM into 2 subgroups according to the positivity or negativity of the anti-LIMA antibodies in the intermediate cells. Among the 41 normal cardias in patients with reflux oesophagitis, 10 contain sulphomucin secreting cells positive with anti-LIMA antibodies. We suggest that this anti-LIMA positivity may be a step preceeding type III IM in specialized epithelium.
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  • 37
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    Virchows Archiv 414 (1989), S. 453-457 
    ISSN: 1432-2307
    Keywords: Ovarian tumours ; Tissue polypeptide antigen ; Light and electron microscopy ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Forty specimens of benign and malignant ovarian tumours were studied for localization of tissue polypeptide antigen (TPA) at light and electron microscopic levels by an indirect immunoperoxidase technique. Of the 30 ovarian carcinomas, 23 (77%) were positive and 7 (23%) were negative for TPA, while of the 10 benign ovarian tumours 3 (30%) were positive and 7 (70%) were negative. Positive reaction did not correlate with the tumour grade. Of the 10 patients with metastasis, 8 (80%) had positive tumours. Staining for TPA was observed at the intraluminal cell surfaces and peripheral cell membranes. The ultrastructural localization of TPA revealed electron-dense reaction products at the cell surface and microvillous surfaces. These results provide confirmatory and supplementary evidence to support the previous findings of TPA in the serum and suggest that testing for TPA in ovarian tumors has a limited prognostic importance and a poor diagnostic value. The surface property of TPA suggests that the cell membrane is involved in secretion and probably synthesis of TPA.
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  • 38
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    Virchows Archiv 415 (1989), S. 91-95 
    ISSN: 1432-2307
    Keywords: Carcinosarcoma ; Urinary bladder ; Immunohistochemistry ; Electron microscopy ; Rhabdomyoblast
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A case of urinary bladder carcinosarcoma (UBCS) is reported with light, immunohistochemical and electron microscopical findings. The tumour consisted of a squamous cell carcinoma, variable spindle cell stromal elements compatible with fibrosarcoma, and rhabdomyoblasts. Intermediate filament co-expression of cytokeratin and vimentin was shown by immunohistochemistry. Electron microscopy (EM) confirmed the nature of the three components, and indicated some similarities between the three cell-types present. Comparisons with the previous UBCS in the literature are made.
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  • 39
    ISSN: 1432-2307
    Keywords: Breast cancer ; tumor markers ; Immunohistochemistry ; Glycolipid antigen ; Neuron-specific enolase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The immunocytochemical reactivity of breast cancers to antibodies raised against neuron-specific enolase (NSE), carcinoembryonic antigen (CEA) and an adenocarcinoma-associated glycolipid antigen (IR-14) was studied in relation to the long-term outcome of the neoplastic disease. The patients whose tumours exhibited reactivity with the IR-14 and anti-NSE antibodies had a considerably better 5-year and long-term survival than those without such reactivity. Assessment of DNA-ploidy of the tumour cells was also relevant for long-term prognosis, immunohistochemistry giving additional prognostic information among aneuploid tumours. Reactivity with polyclonal CEA antibodies was of no prognostic value. It is suggested that tumors carrying the IR-14 reactive epitope, which was originally isolated from circulating antigen-antibody complexes, might evoke a favourable immune response and thus improve the survival of the patient.
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  • 40
    ISSN: 1432-2307
    Keywords: Keratin ; Mammary neoplasms ; Mouse ; Rat ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Using immunoperoxidase staining of monoclonal antibody 312C8-1 against 51 000 dalton human keratin polypeptide, immunolocalization was observed in frozen sections of normal tissue and mammary tumours of adult female mice and rats. In normal tissue, the epitope was recognized in myoepithelial cells of the mammary, sweat and salivary glands, and in basal and suprabasal cells of the epidermis. However, the antibody did not react with luminal epithelial cells of the above glands or with mesenchymal cells. In spontaneous mammary tumours of mice, marker-positive tumour cells were distributed only in the outer layer of adenocarcinoma Type A, while they were scattered in some foci of adenocarcinoma Type B, and encircled the epithelial foci of pregnancy dependent tumours (plaque). All layers of epidermoid structures in adenoacanthoma revealed positivity. In rat mammary tumours induced by local dusting with 7, 12-dimethylbenz(α)anthracene (DMBA) powder, the staining pattern of benign tumours was comparable to that of the normal mammary gland. But, in addition to basally situated cells, marker-positive tumour cells were found scattered in the foci of adenocarcinoma, and were not restricted to basal cells in squamous cell carcinoma. The marker was not found in sarcomatous tissue. This antibody can therefore also be applied to rodents, and the staining pattern can be used to identify the epithelial subclass specific marker in normal tissue and in mammary tumours.
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  • 41
    ISSN: 1432-2307
    Keywords: Trichosporon ; Candida ; Immunohistochemistry ; Autopsy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A case of disseminated trichosporonosis associated with Candida infection of the urinary bladder is presented. Coffee bean shaped or crescent shaped yeast-like elements are characteristic of Trichosporon and useful in differentiating Trichosporon fromCandida but such histological features are less efficient than the immunohistochemistry in identifing mixed fungal infection. In the present case, an application of avidin-biotin-complex (ABC) method with anti -Trichosporon antiserum and anti-Candida antiserum enabled us to diagnose a mixed infection by both fungi.
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  • 42
    ISSN: 1432-2307
    Keywords: Papillary carcinoma of the thyroid ; Intranuclear cytoplasmic inclusions ; Immunohistochemistry ; Thyroglobulin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Intranuclear cytoplasmic inclusions (ICI) in 38 cases of thyroid papillary carcinoma were studied histopathologically, immunohistochemically, and ultrastructurally in order to examine the frequency of ICI and their relationship to both the histological structure and cytological findings in thyroid papillary carcinoma. The fine-structure and biochemical state of ICI were also studied. ICI occurred in all 38 cases. ICI occurrence ranged from one in several microscopic fields to more than ten per field. The number of ICI divided by the number of nuclei on the microscopic photographs ranged from 0.013 to 0.116. The frequency of ICI was strongly influenced by the state of nuclear chromatin and pleomorphism, but was not influenced by a pattern of papillary or follicular tumour growth. Immunohistochemically, 10-30% of ICI revealed strong thyroglobulin (Tg), which was ascertained by immunoelectron microscopy. Neither T3 nor T4 was detected in ICI (with some exceptions). Some ICI showed keratin and vimentin. PAS-positive ICI were observed. Ultrastructurally, enlarged r-ER, many Golgi vesicles and small vesicles (diameter of 300-500 nm) and sacs were observed in ICI. These findings suggested increased protein synthesis and/or protein accumulation Abundant secondary lysozomes, showing degradation of ICI, and bundles of condensed intermediate filaments were also detected. The character and genesis of ICI are discussed.
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  • 43
    ISSN: 1432-2307
    Keywords: Hyperoxia ; Lung broncho-vascular reaction ; Electron microscopy ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In order to clarify the early phenomena involved in the lung reaction to hyperoxia, twenty adult male rats were exposed to 100% oxygen at 1 ATA. Morphological pulmonary lesions were detectable after only 24 h hyperoxia, and included vasoconstriction and perivascular oedema, bronchiolar constriction, and pericyte reaction. The lesions were irregularly scattered within the lung parenchyma and occurred preferentially in areas centred on bronchiolo-vascular stems. Even at the latest stages, pulmonary heterogeneity was obvious, from the coexistence of areas damaged at different times. Neuro-epithelial-bodies were found under the bronchiolar epithelium; the morphological aspect of the neuro-endocrine cells observed was consistent with hyperoxia-induced modulation of their secretory activity. Taken together, our findings show the speed of development of hyperoxia-induced pulmonary changes and raise some pathogenic considerations.
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  • 44
    ISSN: 1432-2307
    Keywords: Cholangitis ; Major histocompatibility complex antigen ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A longitudinal study of intra and extrahepatic bile duct injuries was performed in an animal model of secondary sclerosing cholangitis induced by formalin injection into the common bile duct. Lymphocytic infiltration inside and around the bile ducts occurred seven days after injection. The disease later evolved to a fibrous cholangitis of the small bile ducts. Septal intrahepatic and extrahepatic bile duct involvement became evident three months after formalin injection. The ductular proliferation led to a progressive biliary cirrhosis with portal to portal fibrous septa. After formalin injection, bile duct cells expressed the Ia antigen in the cytoplasm and/or on the membrane of bile duct cells. The intensity of staining did not correlate with the duration or severity of the disease. Lymphocytes infiltrating into and around the bile duct were mainly T-cells. This study suggests that a local cell-mediated immune response to the injection of a toxic agent induces pathological features similar to those of sclerosing cholangitis in man.
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  • 45
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    Virchows Archiv 414 (1989), S. 243-251 
    ISSN: 1432-2307
    Keywords: Ewing's sarcoma ; Histology ; Immunohistochemistry ; Prognostic factors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Histological and immunohistochemical features of 87 patients with conventionally diagnosed Ewing's sarcoma were studied retrospectively on routinely processed material and evaluated with regard to prognostic significance. 74% were convincingly positive when stained for vimentin, 13% were doubtful, and 13% were negative. A varying degree of positivity for neuron-specific enolase (NSE) was found in 15%; these cases all co-expressed vimentin. A single tumour contained scattered cytokeratin-positive cells. Positivity for the leukocyte common antigen (LCA) could be demonstrated in three cases; these were excluded from the statistical analysis of prognostic factors. Growth pattern, soft tissue invasion, monomorphic or dimorphic cell population, and PAS-, NSE- or vimentin-positivity did not influence survival significantly. However, prognosis was increasingly poor with increasing degree of necrosis: median survival was 28 months for grade I necrosis (〈10%), 16 months for grade II (10–50%), and 11 months for grade III (〉50%),p〈0.0005. A mitosis count of 〈1 per high-powerfield (HPF) was correlated to a median survival of 26 months, ≥ 1 per HPF to 12 months,p〈0.05. The findings indicate some degree of heterogeneity in Ewing's sarcoma which may be related to primitive peripheral neuroectodermal tumours (PNETs), or be a true blastoma. In future trials, diagnostic criteria (including immunohistochemistry) should be clearly defined and materials should be large enough to allow for stratification according to prognostic factors.
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  • 46
    ISSN: 1432-2307
    Keywords: Granulomatous inflammation ; Inflammatory pseudotumour ; Immunohistochemistry ; Light microscopy ; Pleura ; Retroperitoneal fibrosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The inflammatory nature of a tumour-like lesion not formerly observed in the parietal pleura was confirmed histologically using immunohistochemical analysis and clinically by spontaneous regression. A study of the literature revealed that the histological picture of the lesion was consistent with that of the rarely described inflammatory pseudotumour.
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  • 47
    ISSN: 1432-2307
    Keywords: Thyroid neoplasms ; Electron microscopy ; Immunohistochemistry ; Calcitonin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary An ultrastructural study, both morphological and immunohistochemical, has been carried out on eight thyroglobulin-positive and nine thyroglobulin-negative medullary carcinomas of the thyroid. The morphometric analysis of granule size showed that all tumours contained cells with small granules and cells with medium size granules, whereas eight tumours had additional cells with large granules. The small granules had an electron dense core, while the medium and large sized granules were both pale-cored and dense-cored. The cells with small, medium or large secretory granules were all immunoreactive for calcitonin and CGRP. No ultrastructural differences were observed between thyroglobulin-positive and thyroglobulin-negative cases of medullary carcinoma of the thyroid.
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  • 48
    ISSN: 1432-2307
    Keywords: Bronchial neoplasms ; Carcinoid ; Immunohistochemistry ; Inclusions
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A bronchial carcinoid with globular intracytoplasmic inclusions is reported. The inclusions stain brown with Grimelius silver impregnation and some show distinct immunoreactivity for chromogranin A. Tumour cells stain positively with antisera to neuron specific enolase, chromogranin A and not with antisera against ACTH, somatostatin or S-100 protein. The cells show distinct immunoreactivity for cytokeratins and vimentin, which is particularly intense in the intracytoplasmic inclusions. Desmin and glial fibrillary acidic protein are absent. Ultrastructural analysis reveals that the inclusions are composed of aggregates of filaments of 8–10 nm of diameter, intrapping a few neurosecretory granules. Immunohistochemical and ultrastructural data support the hypothesis that the inclusions are composed of intermediate filaments, whose metabolism and synthesis have somehow been deranged.
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  • 49
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    Virchows Archiv 415 (1989), S. 219-224 
    ISSN: 1432-2307
    Keywords: Multiple myeloma ; Ectopic amylase production ; Immunohistochemistry ; Immunoelectron microscopy ; Cell culture
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The first autopsy case of amylase-producing IgA-λ-type multiple myeloma is described. Immunohistochemically, amylase and α andλ chains of immunoglobulin were demonstrated in the cytoplasm of the myeloma cells. Secretion of amylase by cultured myeloma cells obtained from the patient's pleural effusion was clearly demonstrated by the starch film method. Immunoelectron microscopically, positive reaction products for amylase and the α chain of immunoglobulin were observed in the well developed endoplasmic reticulum. Since no secretory granules were observed, we postulated that the secretory process of amylase was not via the zymogen granules but via a mechanism similar to that for immunoglobulin.
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  • 50
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    Virchows Archiv 415 (1989), S. 253-258 
    ISSN: 1432-2307
    Keywords: Epithelial markers ; Synovial sarcoma ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Immunohistochemical studies on synovial sarcomas have proved the potentiality of these neoplasm for epithelial and mesenchymal differentiation and antibodies detecting epithelial cells have been found to be helpful in determining the histological types. In this study different epithelial markers directed against various cytokeratins, HMFG-2 and EMA were investigated on paraffin embedded tissues of 13 cases of synovial sarcomas, with regard to their reliability in unmasking the epithelial components demonstrable in this type of neoplasm. The results lead to three conclusions firstly, synovial sarcomas possess the capacity for generating different epithelial cell types with uncommon compositions of intermediate filaments as well as of membrane proteins, secondly, these features may be expressed in a heterogenous pattern even within the same tumour and finally, the use of wide range anti-cytokeratin antibodies covering the spectrum of basic as well as acidic type proteins seems to be necessary for the detection of all epithelial components demonstrable in synovial sarcomas.
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  • 51
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    Virchows Archiv 415 (1989), S. 297-300 
    ISSN: 1432-2307
    Keywords: Non-Hodgkin's lymphoma ; Electron microscopy ; Immunohistochemistry ; Intercellular junction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A rare example of pleomorphic B cell non-Hodgkin's lymphoma is described in which tumour cells possessed simple intercellular junctions.
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  • 52
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    Virchows Archiv 415 (1989), S. 357-366 
    ISSN: 1432-2307
    Keywords: Paraquat poisoning ; Pulmonary fibrosis ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Twenty-nine autopsy cases of paraquat-induced lung injury were studied by histological and immunohistochemical methods. Two stages of injury were identified. In the early stage, the alveolar epithelium degenerates but the epithelial basement membrane remains intact. In the late stage, the epithelial basement membrane is focally disrupted, the mesenchymal cells grow into the alveolar space, and intra-alveolar fibrosis appears. In spite of these pathological changes, the original framework of the alveolar wall is preserved in many areas. Intra-alveolar fibrosis may follow as a consequence of damage to the epithelium without severe damage to the underlying basement membrane, which occurs at the stage of organization. Morphological variants of intra-alveolar fibrosis seem to occur not only to the size of the defect of the basement membrane but also to the difference in the stages of evolution at the time the lesion is studied. The epithelium regenerates along the basement membrane in the early stage of re-epithelialization, but grows over the luminal aspect of intra-alveolar fibrous tissue which has been laid on the remaining basement membrane in the late stage. It is speculated that the regeneration of epithelial cells may develop without any association with the basement membrane when a fibrous tissue covers the original basement membrane.
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  • 53
    ISSN: 1432-2307
    Keywords: Salivary gland ; Myoepithelioma ; Neoplasm ; Electron microscopy ; Immunohistochemistry ; Cytoplasmic filaments
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The histological and ultrastructural features of five major salivary gland tumours, which have little or no evidence of duct- or gland-type differentiation in routine sections, are described. Four of the cases have the tumour cells organized as narrow, anastomosing cords of cells separated by a myxoid and vascularized stroma; we have designated such lesions as reticular-type myoepitheliomas. The fifth case has a solid growth pattern and is largely composed of hyaline cells, that is, a plasmacytoid myoepithelioma. Ultrastructurally, one reticular myoepithelioma reveals myoepithelial cell differentiation with microfilament aggregates, while the other three examples are composed of modified myoepithelial cells displaying widened intercellular spaces, prominent synthesis of extracellular glycosaminoglycans, distinct basal lamina development, and obvious accumulations of cytoplasmic intermediate filaments. In electron micrographs, the modified myoepithelial cells of the plasmacytoid variant closely resemble the tumour cells in the reticular form. Three cases had expression of both glial fibrillary acid protein (GFAP) and vimentin, but only one of the myoepitheliomas contained muscle-specific actin. At least focally, each of the cases exhibited a considerable spectrum of cytokeratin filaments. Using double-labeled immunofluorescent microscopy of one reticular variant and the plasmacytoid myoepithelioma, there was individual tumour cell co-expression of GFAP and vimentin focally in the plasmacytoid myoepithelioma, but co-expression of cytokeratins 13, 16 and GFAP were not noted in either case. As expected, co-expression of high- and low-molecular weight cytokeratin filaments was wide-spread in both myoepitheliomas. Most described myoepitheliomas have a solid growth pattern and are composed of spindle and plasmacytoid cells, but based on cytological features and growth patterns in this series, it is apparent that polygonalshaped cells with novel architecture can occur in myoepitheliomas. The results also indicate the close relationship between pleomorphic adenoma and such variants of myoepithelioma.
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  • 54
    ISSN: 1432-2307
    Keywords: Breast tumours ; Oncogene products ; Immunohistochemistry ; Lymph node metastasis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary It is a matter of debate whether the amplification of c-erbB-2 oncogene or production of the oncoprotein in breast cancers correlate with the presence of lymph node metastasis and with a poor prognosis. This study was aimed at elucidating the immunohistochemical localization of oncogene products which are related to cell growth, c-erbB-2 product, epidermal growth factor receptor (EGFR), c-myc protein and estrogen receptor (ER), in benign and malignant lesions of the breast. Fresh frozen sections of 25 breast cancers and 11 fibroadenomas from Japanese women were studied by indirect immunoperoxidase method with proper fixation. C-erbB-2 product and EGFR were localized on the cell membrane whereas c-myc protein and ER were observed in the nuclei. Immunohistochemical expression of oncogene products and ER were not only observed in the mammary carcinomas but also in the fibroadenomas. However immunoreactivities of EGFR and ER were more frequently seen in the fibroadenomas (p〈0.05). In breast cancers, the incidence of immunoreactivity for c-erbB-2 was higher in the cases with lymph node metastasis than cases without nodal metastasis (p 〈 0.05) and there was reciprocal correlation between the expressions of EGFR and ER (p〈0.05). Regarding the size of the primary tumour, there was no statistically significant correlation with the expressions of c-erbB-2, EGFR, c-myc or ER. Histological grade correlated only with the expression of ER (p〈0.05).
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  • 55
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    Naunyn-Schmiedeberg's archives of pharmacology 339 (1989), S. 178-183 
    ISSN: 1432-1912
    Keywords: Rat ; Urinary bladder ; Somatovesical inhibitory response ; Colovesical inhibitory response ; Capsaicin sensitive afferents
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary (1) The effect of perineal pinching and distension of a balloon inserted into the colon on motility of the urinary bladder has been investigated in adult urethane-anesthetized rats pretreated with capsaicin (50 mg/kg s.c.) or its vehicle 4 days before the experiments. (2) At bladder volumes which were sufficient to elicit reflex micturition, perineal pinching or colonic distension transiently inhibited the ongoing bladder voiding contraction. The somato-vesical inhibitory response was markedly reduced or even abolished by division of pudendal nerves. Neither the somato-vesical nor the colovesical inhibitory response were modified by desensitization with systemically administered capsaicin. (3) Intraurethral administration of capsaicin produced a transient inhibition of the reflexly-activated bladder contractions. A second administration of the drug was less effective, indicating desensitization. Intravenously administered capsaicin had a similar inhibitory effect on bladder motility. (4) The vesico-inhibitory response produced by intraurethral administration of capsaicin was not affected by phentolamine, propranolol, guanethidine, picrotoxin or naloxone, while it was greatly reduced or even abolished by bilateral section of the pudendal nerves. (5) These findings provide evidence that capsaicin-sensitive chemoreceptors in the rat urethra are involved in generating a vesico-inhibitory response via pudendal nerves. On the other hand, no evidence was found for the participation of capsaicin-sensitive nerves in the generation of the somato- or colo-vesical inhibitory response.
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  • 56
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    Naunyn-Schmiedeberg's archives of pharmacology 339 (1989), S. 551-556 
    ISSN: 1432-1912
    Keywords: Dopamine ; 5-HT synthesis ; Brain ; 8-OHDPAT ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Regional dopamine synthesis in the rat striatum was estimated by measuring DOPA accumulation following inhibition of cerebral aromatic l-amino acid decarboxylase by means of NSD-1015, 100 mg kg−1 intraperitoneally. In animals treated with reserpine, 5 mg kg−1 subcutaneously −18 h, there was a statistically significant increase in DOPA accumulation in the nucleus accumbens, the ventro-medial neostriatum, the dorso-lateral neostriatum and in the posterior limb of the neostriatum. This increase in DOPA accumulation was antagonized dose-dependently in the nucleus accumbens and ventro-medial neostriatum, but not in the other two regions, by treatment with the 5-HT1A receptor agonist 8-OH-DPAT, 0.15–2.4 μmol kg−1, whereas the partial dopamine D2 receptor agonist (−)3-PPP, 2.5–10.0 μmol kg−1, or the full dopamine D2 receptor agonist quinpirole, 0.05–0.8 μmol kg−, antagonized the reserpine-induced increase in DOPA accumulation uniformly in all four regions of the striatum. The suppression of DOPA accumulation by 8-OH-DPAT in reserpine-treated animals, was completely antagonized by raclopride, 1 μmol kg−1, but not by (−)pindolol, 8 μmol kg−1. The accumulation of 5-HTP in all regions of the striatum as well as in the neocortex following decarboxylase inhibition and reserpine pretreatment, was also inhibited by 8-OH-DPAT, and this inhibition was unaffected by treatment with raclopride or (−)pindolol. It is concluded that 8-OH-DPAT, in addition to general effects on forebrain 5-hydroxytryptamine synthesis, selectively affects limbic forebrain dopamine synthesis. This latter effect is probably due to direct stimulation of dopamine autoreceptors, since it was obtained in reserpine-treated rats, and was completely antagonized by raclopride, but not (−)pindolol.
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  • 57
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    Naunyn-Schmiedeberg's archives of pharmacology 339 (1989), S. 312-314 
    ISSN: 1432-1912
    Keywords: Locus coeruleus ; Rat ; Excitatory amino acids ; Kynurenic acid ; Mg2+
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The goal of this study was to investigate whether locus coeruleus neurons of the rat are sensitive to agonists of the different excitatory amino acid receptors. All experiments were performed on a midpontine rat slice preparation. Bath-applied l-glutamate, kainate, N-methyl-d-aspartate (NMDA) and quisqualate induced concentration-dependent activations of all neurons which were reflected in an increase of the neurons' mean discharge rate. The rank order of cell activation was kainate ∼ quisqualate 〉 NMDA 〉 l-glutamate. None of the agonists induced a bursting-type of discharge. The NMDA-receptor blocker dl-2-amino-5-phosphonovaleric acid (APV, 30 μM) selectively antagonized the NMDA-induced increase in cell firing. Kynurenic acid (100 μM) non-selectively attenuated the response to NMDA, kainate and quisqualate. Neither APV nor kynurenic acid per se had any effect on the spontaneous firing rate. If the Mg2+ concentration in the superfusion medium was lowered from 2 mM to nominally zero the response to NMDA was selectively increased. In conclusion, locus coeruleus neurons share with other neurons their sensitivity to agonists of all three types of excitatory amino acid receptors. However, in contrast to other neurons, they do not respond with a bursting type of discharge.
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  • 58
    ISSN: 1432-1912
    Keywords: Rat ; Forebrain ischemia ; Local cerebral blood flow ; Neuronal damage ; Emopamil
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effects of the calcium entry blocker emopamil on physiological variables, local cerebral blood flow (LCBF) and on hippocampal cell damage were evaluated after 10 min of forebrain ischemia in the rat. LCBF was determined with the 14C-iodoantipyrine technique after 2, 10, and 60 min of postischemic recirculation. Histological evaluation was performed 7 days after ischemia in cortical and hippocampal tissue by determination of the percentage of necrotic neurons. Preischemic application of emopamil [4 mg/kg racemate or 2 mg/kg (S)-emopamil; i.v.] caused increases in LCBF in cortical areas but did not alter blood flow in the hippocampus at 2 min of recirculation. After 10 and 30 min of flow resumption no differences in LCBF between drug-treated and control animals were observed. In the histological series (S)-emopamil was applied at doses of 2, 4 or 6 mg/kg before the induction of ischemia. After 7 days of postischemic recovery, neuronal damage was significantly reduced by the calcium antagonist in hippocampal CA 1 sector at all doses tested, the most prominent effects being observed with the lowest dose. At this dose cell loss in the Ca3 sector was also reduced. In cortical tissue the number of necrotic cells remained unchanged by emopamil treatment. It is concluded that the calcium antagonist emopamil can reduce ischemia-induced neuronal cell damage. The compound improves circulation in cortical tissue only during early recovery but not at later phases of reflow, i.e. the period of delayed hypoperfusion. These increases in blood flow are not of crucial importance for ultimate neuronal death in this area. The ameliorative action of emopamil on the survival of hippocampal neurons is not associated with blood flow changes and therefore seems to reflect a direct effect on cerebral parenchyma.
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  • 59
    ISSN: 1432-1432
    Keywords: Carcinoembryonic antigen ; Evolution ; Gene family ; Human ; Rat ; Synonymous substitutions ; Silent molecular clock ; Evolutionary trees
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary Various rodent and primate DNAs exhibit a stronger intra- than interspecies cross-hybridization with probes derived from the N-terminal domain exons of human and rat carcinoembryonic antigen (CEA)-like genes. Southern analyses also reveal that the human and rat CEA gene families are of similar complexity. We counted at least 10 different genes per human haploid genome. In the rat, approximately seven to nine different N-terminal domain exons that presumably represent different genes appear to be present. We were able to assign the corresponding genomic restriction endonuclease fragments to already isolated CEA gene family members of both human and rat. Highly similar subgroups, as found within the human CEA gene family, seem to be absent from the rat genome. Hybridization with an intron probe from the human nonspecific cross-reacting antigen (NCA) gene and analysis of DNA sequence data indicate the conservation of noncoding regions among CEA-like genes within primates, implicating that whole gene units may have been duplicated. With the help of a computer program and by calculating the rate of synonymous substitutions, evolutionary trees have been derived. From this, we propose that an independent parallel evolution, leading to different CEA gene families, must have taken place in, at least, the primate and rodent orders.
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  • 60
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    Pediatric nephrology 3 (1989), S. 149-155 
    ISSN: 1432-198X
    Keywords: Cationized bovine serum albumin ; Glomerular capillary wall polyanion ; Serum sickness glomerulopathy ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of injected native and cationized bovine serum albumin (BSA− and BSA+ respectively) were evaluated in rats which subsequently received anti-BSA. Thrombocytopenia, low creatinine clearance (Ccr), increased proteinuria, capillary swelling, mild tuft necrosis and BSA+ deposits in glomeruli resulted within 24 h of BSA+ injection. Later BSA+ produced mesangial expansion glomerular capillary wall (GCW) thickening and deposits of BSA+ accompanied by rabbit anti-BSA and rat anti-BSA which correlated well with small mesangial, subendothelial and subepithelial electron-dense granular accumuli. These latter enlarged considerably after the injection of anti-BSA. BSA− controls showed minimal or no lesions. The disappearance from the blood (t1/2) of a single dose of immune complexes (IC) prepared with chromatography-purified, radioiodinated anti-BSA-BSA− and BSA+ was determined in another group of rats. The t1/2 of BSA− anti-BSA was 42.8 h (95% confidence: 39.8–46.2) while that of BSA+ anti-BSA was 52.5 h (48.1–57.8). These results suggested that serum sickness glomerulitis developed only in rats injected with BSA+, due to in situ IC which presumably grew by accretion of foreign anti-BSA. Circulating IC may have developed and colocated with the latter, with dissociation and recombination at these sites. It is postulated that the functional-immunomorphological changes and the slow removal of cationized IC reported herein could be explained by the highly positive net charge of the injected antigen.
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  • 61
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    Naunyn-Schmiedeberg's archives of pharmacology 340 (1989), S. 239-245 
    ISSN: 1432-1912
    Keywords: Intestinal absorption ; Vascular perfusion ; Glucuronidation ; 1-Naphthol ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Using the isolated vascularly fluorocarbon emulsion perfused rat small intestine some factors which determine the extent of the intestinal glucuronidation of 1-naphthol to 1-naphthol-β-d-glucuronide were studied. Increasing the luminal 1-naphthol concentration resulted in a concomitant increase in the 1-naphthol appearance in the vascular perfusate. In contrast, the total appearance of 1-naphthol-β-d-glucuronide increased less than proportional to the increase in the luminal 1-naphthol concentration. About 88% of the total amount of 1-naphthol-β-d-glucuronide excreted was released into the vascular perfusate. The capacity-limited intestinal glucuronide efflux is most likely due to saturation of the excretory mechanism for 1-naphthol-β-d-glucuronide. Decreasing the vascular flow rate influenced both the appearance of 1-naphthol and 1-naphtol-β-d-glucuronide in the vascular perfusate, whereas the appearance of 1-naphthol-β-d-glucuronide in the luminal perfusate was essentially flow-independent. A noradrenaline-induced change in the haemodynamic state of the vascular bed (with the total flow kept constant) resulted in a marked decrease in the 1-naphthol vascular concentration. The vascular 1-naphthol-β-d-glucuronide concentration was only slightly affected. These results indicate that changes in blood flow and blood flow distribution within the intestinal wall can affect the extent of presystemic intestinal metabolism by interfering with the absorption of the parent compound and the efflux of formed conjugates. These parameters can be of paramount importance for causing variable intestinal first-pass effects of drugs in vivo.
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  • 62
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    Naunyn-Schmiedeberg's archives of pharmacology 340 (1989), S. 541-546 
    ISSN: 1432-1912
    Keywords: Ruthenium Red ; Capsaicin ; Sensory nerves ; Rat ; Urinary bladder
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary (1) Topical administration of Ruthenium Red (10–100 μM in saline) to the serosal surface of the urinary bladder in urethane-anesthetized rats prevented the motor response of the urinary bladder to topical administration of capsaicin and protected the sensory fibers from capsaicin desensitization, but had no effect on the volume-evoked contractions (micturition reflex). At 1 mM increased bladder capacity and decreased amplitude of micturition contraction were observed. (2) At 100 μM, topical Ruthenium Red prevented the blood pressure rise produced by topical administration of capsaicin onto the bladder but did not affect the blood pressure rise produced by sudden bladder distension in spinal rats. (3) After intrathecal administration, Ruthenium Red (80–800 ng/rat) produced a long lasting inhibition of the micturition reflex in urethane-anesthetized rats, this effect being evident in both vehicleor capsaicin- (50 mg/kg s. c. 4 days before) pretreated rats. At 800 ng/rat, intrathecal Ruthenium Red did not affect the blood pressure rise produced by topical administration of capsaicin onto the rat bladder nor that produced by bladder distension. (4) These findings provide further evidence that Ruthenium Red acts quite selectively as a “capsaicin antagonist” preventing both reflex and “efferent” responses activated by peripherally administered capsaicin. By contrast, sensory impulse generation by a natural stimulus such as bladder distension is apparently unaffected by Ruthenium Red. The marked inhibition of the micturition reflex observed after intrathecal administration of Ruthenium Red does probably not involve an interaction with primary afferents in the spinal cord.
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  • 63
    ISSN: 1432-1912
    Keywords: Intestinal absorption ; 1-Naphthol ; Glucuronidation ; Rat ; Albumin binding
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Using an isolated vasculary perfused rat small intestine we studied the role of luminal flow rate and intraluminal binding on the absorption of 1-naphthol (1-N) and the intestinal metabolism of 1-N to 1-naphthol-β-d-glucuronide (1-NG). Raising the luminal perfusion rate resulted in a decrease in the luminal 1-N extraction ratio and an increase in the luminal 1-N clearance Cl lum. The dependency of Cl lum on flow rate appeared to conform to a convective diffusion model. A differential susceptibility of 1-N absorption and the total 1-NG appearance to the luminal flow rate resulted in a flow-dependent first-pass effect of 1-N. Next, the effect of intraluminal binding on 1-N disposition was studied in experiments in which albumin was added to the luminal perfusion fluid. The unbound concentration, as the driving force for the uptake of 1-N, seems not to be rate-limiting for the appearance of 1-NG. The total appearance of 1-NG in the presence of albumin was greater than would be anticipated from the free concentration of 1-N. As a result the extent of presystemic extraction increased with increasing albumin concentration. The precise mechanisms responsible for the phenomenona are not entirely clear. Consideration of the heterogeneity in the glucuronidation capacity along the rat small intestine and along the crypt-villus axis can help to explain the obtained results.
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  • 64
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    Naunyn-Schmiedeberg's archives of pharmacology 340 (1989), S. 161-169 
    ISSN: 1432-1912
    Keywords: Amperozide ; Rat ; Behavioural stimulation ; Monoamines ; Biochemical effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Amperozide (FG 5606; N-ethyl-4-[4′,4′-bis(p-fluorophenyl) butyl]-1-piperazinecarboximide) is a new putatively antipsychotic compound with a postulated 5-HT2 antagonistic profile. Somewhat surprisingly amperozide dose dependently induced a behavioural stimulation in reserpinized and in nonpretreated rats. The behaviour consisted of both forward and backward locomotion as well as forepaw circling and a grooming like behaviour. Since the behavioural pattern clearly differ from that produced by classical dopaminergic or serotonergic agonists (e. g. apomorphine or 8-hydroxy-2-(di-n-propylamino)tetralin, 8-OH-DPAT), and has not been previously reported, we decided to investigate the origin of this effect. In the behavioural paradigms it was not possible to antagonize the amperozide stimulation in reserpinized rats with the dopamine receptor blockers haloperidol, raclopride or R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1 H-3-benzazepine, SCH 23390. Neither the 5-HT2 receptor blocking agent ritanserin nor the tryptophan and tyrosine hydroxylase inhibitor DL-3,4-dihydroxy-phenyl-α-propylacetamide, H22/54, could block the motoric stimulation or the forepaw circling behaviour produced by amperozide. However, the noradrenaline synthesis inhibitor bis- (4-methyl-1-homopiperazinylthiocarbonyl)-disulfide, FLA 63, as well as the α-adrenoceptor antagonist phenoxy-benzamine, could partly inhibit the locomotor stimulation. Hence, noradrenaline seems to be, at least in part, involved in the behavioural stimulatory effect of amperozide. synthesis rate (DOPA formation) in normal or reserpinized animals in the striatal or the limbic brain regions. In reserpinized animals amperozide also failed to antagonize the decrease in DOPA formation after apomorphine and 3-hydroxy-benzylhydrazine HCl, NSD 1015, in these regions. Thus, amperozide failed to show agonistic or antagonistic action on central dopamine receptors. However, in the noradrenaline rich cortical region amperozide induced an increase in DOPA accumulation. The compound also increased the levels of normetanephrine as well as antagonized the decrease in DOPA accumulation by clonidine in the cortical brain region. Amperozide also increased the disappearence rate of noradrenaline after inhibitor of tyrosine hydroxylase by α-methyl-para-tyrosine. These data suggest that, biochemically, amperozide has got α2 antagonistic properties. However, it is not evident that these biochemical properties are responsible for the behavioural effects of amperozide.
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  • 65
    ISSN: 1432-1351
    Keywords: Rat ; Melatonin ; Circadian rhythm ; 5-hydroxytryptophan
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The rhythm in melatonin production in the rat is driven by a circadian rhythm in the pineal N-acetyltransferase (NAT) activity. Rats adapted to an artificial lighting regime of 12 h of light and 12 h of darkness per day were exposed to an 8-h advance of the light-dark regime accomplished by the shortening of one dark period; the effect of melatonin, triazolam and fluoxetine, together with 5-hydroxytryptophan, on the reentrainment of the NAT rhythm was studied. In control rats, the NAT rhythm was abolished during the first 3 cycles following the advance shift. It reappeared during the 4th cycle; however, the phase relationship between the evening rise in activity and the morning decline was still compressed. Melatonin accelerated the NAT rhythm reentrainment. In rats treated chronically with melatonin at the new dark onset, the rhythm had already reappeared during the 3rd cycle, in the middle of the advanced night, and during the 4th cycle, the phase relationship between the evening onset and the morning decline of the NAT activity was the same as before the advance shift. In rats treated chronically with melatonin at the old dark onset or in those treated with melatonin 8 h, 5 h and 2 h after the new dark onset during the 1st, 2nd and 3rd cycle, respectively, following the advance shift, the NAT rhythm reappeared during the 3rd cycle as well but in the last third of the advanced night only. Neither triazolam nor fluoxetine together with 5-hydroxytryptophan administered around the new dark onset facilitated NAT rhythm reentrainment after the 8-h advance of the light-dark cycle.
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  • 66
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    Archives of gynecology and obstetrics 244 (1989), S. 151-155 
    ISSN: 1432-0711
    Keywords: Placenta ; Glycogen ; Triglyceride ; Cold ; Fasting ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effect of exposure to cold (+2°C, 3 and 24 h) and fasting (1, 2 and 3 days) on placental glycogen and triglyceride content was investigated in rats pregnant for 20 days. The stimuli did not affect the level of glycogen in the placenta. The level of triglycerides remained unchanged in the rats exposed to cold. It rose after only one day of fasting and then levelled out on the 2nd and 3rd days. Fasting, but not exposure to cold produced hypoglycemia and elevation of the plasma free fatty acids level. We conclude that activation of the adrenergic system during exposure to cold does not interfere with the glycogen and triglyceride content of the placenta. Prolonged hypoglycemia also does not affect the placental glycogen level although it increases the accumulation of neutral fat.
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  • 67
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    Archives of gynecology and obstetrics 246 (1989), S. 61-84 
    ISSN: 1432-0711
    Keywords: Immunohistochemistry ; Uterine cervix ; Epithelial markers ; Cervical carcinogenesis ; Monoclonal antibodies
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Epithelial antigen immunostaining in the uterine cervix has been claimed to be helful in the identification and classification of rare lesions, evaluation of basement membrane integrity, study of atypical condylomas, immunodetection of proliferating processes and early diagnosis of malignant transformation. The present review attempts to demonstrate the potential value of immunohistological techniques as a means of identifying normal and abnormal patterns of antigenic expression in cervical epithelium.
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  • 68
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    Archives of toxicology 63 (1989), S. 43-46 
    ISSN: 1432-0738
    Keywords: Styrene ; Testes ; Rat ; Enzymes ; Toxicity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Styrene was administered through gavage to adult male rats for 60 days. At the lower dose of 200 mg/ kg/day no overt signs of testicular toxicity were observed, while at the higher dose of 400 mg/kg/day activities of some marker enzymes for testicular function were found to be altered significantly, along with a decrease in spermatozoa number. Histopathological studies revealed marked degeneration of seminiferous tubules and lumen devoid of sperms, further confirming testicular toxicity of styrene. The present study suggests an overall sensitivity of the male reproductive system towards styrene exposure.
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  • 69
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    Archives of toxicology 63 (1989), S. 320-324 
    ISSN: 1432-0738
    Keywords: Cadmium ; Rat ; Mechanical strength of bones
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The mechanical properties of the bones of young, adult and old rats administered various concentrations of cadmium were measured to prove the direct effect of cadmium on the bones of young rats. The young rats were divided into three subgroups, which were administered 0 (control), 5 and 10 ppm cadmium, respectively. The adult rats were subdivided into six groups, administered 0, 10, 20, 40, 80 and 160 ppm cadmium, respectively. The old rats were divided into three subgroups, which were administered 0, 80, and 160 ppm cadmium, respectively. The length of the administration was 4 weeks in every group. The decrease in the mechanical strengths of bones of young rats administered with cadmium was observed. On the other hand, no change in mechanical strength of bones was observed in the case of adult and old rats, administered up to 160 ppm cadmium. The correlation between the cadmium in bones and the decrease in the strength of the bone shows that cadmium directly affects the mechanical properties of bones of young rats.
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  • 70
    ISSN: 1432-0533
    Keywords: Serotonin ; Neostriatum ; Hyperthermia ; Seizure ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Changes occurring in serotonin neurons during hyperthermia and hyperthermia-induced convulsions were examined by quantiative immunohistochemistry. A marked increase in serotonin immunoreactivity was observed at the rostral and intermediate levels of the neostriatum of mice kept at high temperatures with no convulsions, and a significant reduction in serotonin immunoreactivity was verified throughout the neostiatum of mice which had hyperthermia-induced seizures. These results suggest that serotonin neurons change significantly during thermal stress and seizures, and that regional analysis is essential for an understanding of the role of serotonin neurons.
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  • 71
    ISSN: 1432-0533
    Keywords: Gangliocytoma ; Ganglioglioma ; Ultrastructure ; Immunohistochemistry ; Neuroendocrine markers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We studied five cases of central nervous system neuronal tumor, one gangliocytoma and four gangliogliomas, both ultrastructurally and immuno-histochemically, using antibodies to neuroendocrine markers including tyrosine hydroxylase (TH), serotonin (5HT), somatostatin (SOM), met-enkephalin (MEK), leu-enkephalin (LEK), substance P (SP), gastrin, vasopressin, oxytocin, vasoactive intestinal polypeptide, adrenocorticotropic hormone and calcitonin. In all cases, the presence of dense-core vesicles (60–250 nm) in the neuronal elements was the characteristic ultrastructural finding. Synapses were observed in two cases. Immunohistochemically, variable numbers of neuronal cells showed positive staining for SOM in five cases, TH, MEK and LEK in three cases, and 5HT and SP in one case each. The others were negative. Positive immunoreactivity for multiple markers was shown in all cases. SOM, TH, 5HT and SP were present in the small- to medium-sized cells, while MEK and LEK were almost exclusively confined to the large cells. Our study clearly indicated that these tumors contained neuronal cells which were not homogeneous with regard to neuroendocrine markers.
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  • 72
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    Anatomy and embryology 180 (1989), S. 143-149 
    ISSN: 1432-0568
    Keywords: Development ; Adenohypophysis ; Immunohistochemistry ; Lizard ; Gallotia galloti
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Immunohistochemical methods have been used to study the embryonic and postnatal development of the hormone-producing cells in the adenohypophysis of the lizard Gallotia galloti. In this species, Rathke's pouch is formed between stages 30 to 32 of the embryonic development, although the first sign of immunoreactivity to antisera against adenohypophysial hormones occurs in stage 33 in the pars distalis anlage. These cells derive from the dorsal face of Rathke's pouch and are immunoreactive to anti-ACTH serum. The cytodifferentiation of ACTH and MSH cells occurs in the pars intermedia in stage 34. The TSH cells appear at stage 35 and the gonadotrope cells at stage 37. These cells derive from both the dorsal and ventral face of the Rathke's pouch. The LTH cells are revealed at stage 39 and are only originated from the dorsal face. The STH cells, which come from the dorsal as well as ventral face, are the last secretory cells differentiated just before hatching. During postnatal development an increase and also a redistribution of the immunoreactive cells occur until acquiring the adult distribution.
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  • 73
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    Anatomy and embryology 180 (1989), S. 159-163 
    ISSN: 1432-0568
    Keywords: Ontogeny ; Neuron-specific enolase ; Taste buds ; Vallate papillae ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The detailed morphology of the nerve fibers and the taste bud cells in developing vallate papillae of the rat tongue was investigated utilizing the immunoperoxidase technique to detect neuron-specific enolase (NSE). For convenience of description, five stages of development were defined: Stage 1, the fifteenth and the sixteenth embryonic day (E15–E16): NSE like immunoreactive (NSE-) nerve fibers, with some random arborization, appeared around the median lingual sulcus at the base of the tongue; Stage 2 (E16–E17): NSE-nerve fibers invading the central core of newly formed vallate papilla and underlying the apical epithelium of the papilla; Stage 3 (E18–E21): round-shaped undifferentiated NSE-taste bud cells appearing in the apical epithelium; Stage 4, the first day of postnatal age (P1): NSE-taste bud cells migrated to the side epithelium, lining the gutter beneath which the nerve plexus formed during E18–E21, and extended cytoplasmic process toward the surface and/or the basal lamina; Stage 5 (P3–P5): NSE-nerve fibers and spindle-shaped NSE-taste bud cells with a typical figure of taste bud cells appeared in newly formed taste buds in the side epithelium, lining the gutter. The sequential topographic development of nerve preceding NSE-taste bud cells in precise morphological locations, suggests that the ingress of precursor NSE-taste bud cells and their subsequent differentiation are contingent upon initial neural derived ontologic signals.
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  • 74
    ISSN: 1432-0568
    Keywords: Pyramidal tract ; Rat ; Development ; Axon loss ; Myelination
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A quantitative electron microscopic analysis was undertaken of the development of the pyramidal tract, at the level of the third cervical spinal segment, in rats ranging in age from the day of birth to three months old. The axon number was calculated as the product of axon density, determined in a systematic random sample of electron micrographs, and tract area. During the first postnatal week the tract contains thin unmyelinated axons and growth cones. Growth cones are abundant in neonatal rats, but can still be observed occasionally at the end of the first postnatal week, indicating a continuous addition of pyramidal tract axons during the first postnatal week. Myelination starts around P10. By the end of the first postnatal month approximately 50% of the axons have already been myelinated. Myelination proceeds during further maturation, but in the three month old rat 28% of the axons are still unmyelinated. The total number of axons increases rapidly after birth up to 153 000 at the fourth postnatal day. Subsequently, the number of axons is reduced by nearly 50% to 79 000 in the adult rat. The axon loss is most prominent during the second postnatal week, when 32 000 axons are climinated, but continues for several weeks at a slower rate.
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  • 75
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    Anatomy and embryology 179 (1989), S. 387-393 
    ISSN: 1432-0568
    Keywords: Distribution pattern ; Creatine kinase isozymes ; Embryonic chicken heart ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The distribution pattern of creatine kinase (EC 2.7.3.2) isozymes in developing chicken heart was studied by immunohistochemistry. Creatine kinase M, which is absent from adult heart, is transiently expressed between 4 and 11 days of incubation. During that period, numerous muscular cells in the roof and septum of the atrium, in the interventricular septum and on top of the trabeculae cordis and at the rim of the outflow tract stain strongly with a polyclonal antibody that is specific for the M subunit. In the ventricle and outflow tract, the M-positive cells are found mainly subendocardially and in the right half, at the transition of conducting and working myocytes. Creatine kinase B, which is the predominant adult isozyme, is initially expressed to a high concentration in a small group of disperse myocardial cells in the upstream part of the inflow tract. When compared to the expression pattern of cardiac myosin heavy chains, the observed creatine kinase expression pattern suggests that M-positive cells are mainly found in areas that participate in the formation of cardiac conductive tissue, whereas B-positive cells are first found in areas that are involved in the generation of cardiac rhythm.
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  • 76
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    Acta neuropathologica 77 (1989), S. 258-266 
    ISSN: 1432-0533
    Keywords: Neurofibrillary tangles ; Alzheimer's disease ; Pick bodies ; Immunohistochemistry ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We have studied the immunohistochemical reactivity and ultrastructure of both neurofibrillary tangles (NFTs) occurring with severe neurofibrillary diseases, and Pick bodies (PBs) associated with Pick's disease. The NFTs and PBs did not react immunohistochemically with the anti-nonphosphorylated neurofilament monoclonal antibody irrespective of whether they were pretreated with alkaline phosphatase. In granular neurons of the dentate fascia of Ammon's horn in cases of dementia of the Alzheimer type (DAT), NFTs either resembled PB-like inclusion bodies (Horoupian's inclusion bodies) in form, or had a perinuclear structure. Immunohistochemically and ultrastructurally, the NFTs in the dentate fascia in cases of DAT, including Horoupian's inclusion bodies, were similar to the NFTs in the pyramidal neurons of Ammon's horn, which are found most frequently in association with severe neurofibrillary diseases. Under a light microscope, Horoupian's inclusion bodies and PBs could not be differentiated and appeared to be argyrophilic round cytoplasmic inclusions in granular neurons of the dentate fascia. There were, however, ultrastructural differences. Horoupian's inclusion bodies consisted of bundles made up of straight tubules (STs), each about 15 nm in diameter. These bundles were intermixed with a few paired helical filaments which occurred at intervals of about 80 nm. On the other hand, PBs were composed of randomly distributed 15-nm-wide STs, intermixed with a very few fibrillary structures. These fibrils had a periodicity of about 160 nm, and ranged in width from about 15 nm to 30 nm. Horoupian's inclusion bodies associated with DAT and PBs associated with Pick's disease are different in this neuropathological aspect. The NFTs, including Horoupian's inclusion bodies in the dentate fascia in cases of DAT, are considered to be a manifestation of neurofibrillary degeneration.
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  • 77
    ISSN: 1432-0533
    Keywords: Purkinje cell ; Immunohistochemistry ; Axon ; Phenytoin ; Mouse
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The present study describes the identification and the ultrastructural and numerical evolution of Purkinje cell axonal swellings induced by phenytion. Thirty male C57BI/6J mice received phenytion orally in doses up to 100 mg/kg daily and were killed after 3, 6, 10, 14, and 48 days of treatment. Light and electron microscopic investigations as well as morphometric analysis of cut surface area and numerical density of axonal swellings were performed. The swellings appeared as early as 6 days after initiation of treatment and gradually increased in size and frequency. Use of an anti-lymphocyte monoclonal antibody (CD 3), specifically cross-reacting with Purkinje cells, identified the swellings as dystrophic Purkinje cell axons. On grounds of their ultrastructural appearance they were classified into three distinct types occurring at different time intervals after phenytoin exposure. At 6 days, most axonal swellings contained loosely aggregated membranous vesicles and tubules in a finely granulated matrix (type 1). At 14 days, larger axonal swellings appeared characterized by the presence of three-dimensional networks of branched and anastomosing membranous tubules (type 2). At 48 days, even larger axons contained bodies of highly condensed membranous material of sometimes paracrystalline appearance (type 3). It is suggested that phenytoin-induced axonal pathology of Purkinje cells is a dynamic process characterized by the progressive accumulation of proliferating membranous material arranged in an increasingly complex fashion.
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  • 78
    ISSN: 1432-0533
    Keywords: Blood-brain barrier ; Bromodeoxyuridine ; Cerebral endothelium ; Immunohistochemistry ; Regeneration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary It is still unknown when and in which area endothelial regeneration occurs after brain injury, and to what extent such changes depend on the severity of the injury. We have, therefore, studied bromodeoxyuridine (BrdU) uptake by regenerating endothelial cells in two different groups of rats given cold lesions using immunohistochemistry employing anti-BrdU monoclonal antibody, anti-factor VIII-related antigen antibody and anti-glial fibrillary acidic protein antibody. The earliest evidence for the presence of BrdU-positive endothelial cells (BrdU+end) was observed at 2 days after injury, the injured endothelial cells regenerating from the edge toward the center of the lesion in both groups. We considered that edema fluid could act as an important factor, since at 2 days post-injury BrdU+end were not in contact with macrophages and were always found in Evans blue-stained areas. Study of endothelial cell kinetics also confirmed that the repair of injured endothelial cells was intimately involved in the reconstruction of the blood-brain barrier, since the time of disappearance of BrdU+end coincided with the disappearance of Evans blue-stained areas. The difference in the process of endothelial regeneration was first apparent on the 3rd day, there being no difference at 2 days.
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  • 79
    ISSN: 1432-0533
    Keywords: Experimental allergic neuritis ; Monocytes ; Immunohistochemistry ; Electrophysiology ; Resident dendritic cell
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Electrophysiological, clinical and histological techniques were used to monitor the time course of events related to experimental allergic neuritis (EAN) in 48 Lewis rats. The primary lesion was found to be paranodal demyelination without cellular infiltration. Endoneural phagocytes derive from hematogenous ED1+ED2− monocytes and possibly from resident ED1− ED2+ monocytic cells, not from Schwann cells and fibroblasts. We demonstrate a population of monocytic Ia-bearing, ED1−ED2+ spindle-shaped cells residing in normal peripheral nerve and provide evidence for their transformation into macrophages in the course of EAN.
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  • 80
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    Acta neuropathologica 77 (1989), S. 569-575 
    ISSN: 1432-0533
    Keywords: Monoclonal antibody ; Microglial cells ; Alzheimer's disease ; Senile plaques ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A monoclonal antibody, termed AD11/8, reactive to microglial cells, was produced by immunization of mice with partially purified amyloid fibrils of senile (neuritic) plaques. With immunoperoxidase staining on human tissues, AD11/8 also recognized macrophages in the red pulp of the spleen, Kupffer cells in the liver, and macrophages in the bone marrow. The results show that AD11/8 recognizes the antigens associated with mononuclear phagocytes lineage. In normal brains a few resting microglial cells were stained in gray matter, and less frequently in white matter. In senile dementia of the Alzheimer type numerous microglial cells were stained intensively and they often formed clusters in gray matter. By double immunostaining with AD11/8 and a polyclonal antibody against synthetic amyloid β-protein, clustered microglial cells were observed in and around senile plaques with amyloid deposits. Some amyloid plaque cores were surrounded by microglial cell processes. These results indicate that microglial cells may play an important role in senile plaque formation.
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  • 81
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    Acta neuropathologica 79 (1989), S. 129-136 
    ISSN: 1432-0533
    Keywords: Ferritin ; Microglia ; Immunohistochemistry ; Scrapie-associated fibrils
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary An immunohistochemical analysis of formalin-fixed, paraffin-embedded brain sections was performed with antisera against holoferritin and the light(L)-subunit of ferritin. Sections immunostained using anti-glial fibrillary acidic protein (GFAP), Ricinus communis agglutinin-1 (RCA-1) stain for microglia and iron stain (Berlin blue stain) were compared. The L-subunit of ferritin was purified from normal human spleen according to the modified scrapie-associated fibrils purification, and the antiserum was raised in a rabbit. Both ferritin antisera positively stained resting and, more markedly, reactive microglia, both of which were also stained with RCA-1 but not with GFAP. Ferritin-positive resting microglia were seen more abundantly in cerebral and cerebellar cortices than in white matter. The advantages of ferritin antisera over RCA-1 are as follows. (1) RCA-1 heavily stains blood vessels, while anti-ferritin does not, hence the microglial cells are more readily visualized with ferritin immunohistochemistry. (2) Reactive microglia and macrophages are more strongly stained with anti-ferritin. (3) The staining intensity of ferritin is independent of the length of tissue fixation in formalin. However, anti-ferritin is inferior to RCA-1 in staining resting microglia with a scanty cytoplasm, especially in the white matter, probably because the former recognizes cytoplasmic components, while the latter recognizes cell membrane. Iron stain only gave a reaction to microglial cells in brains with neurosyphilis and to hemosiderin-laden macrophages. Thus, in addition to RCA-1, ferritin antisera are useful as a microglia marker in formalin-fixed, paraffin-embedded sections.
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  • 82
    ISSN: 1432-0533
    Keywords: Neurofibromatosis 2 ; Bilateral acoustic neurofibromatosis ; Ghal hamartomas ; Immunohistochemistry ; S-100 protein
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Bilateral acoustic neurofibromatosis (neurofibromatosis 2, NF2) accounts for less than 10% of all cases of neurofibromatosis and manifests itself with bilateral acoustic schwannomas, multiple schwannomas of spinal nerve roots, meningiomas, glial tumors and hamartomatous CNS lesions. We have observed dysplastic foci of immature neuroectodermal cells in the cerebral cortex and basal ganglia of six patients afflicted with neurofibromatosis 2, ranging from occasional clusters of immature, dysplastic cells to numerous, confluent lesions. These cells, although often polymorphic and multinuclear did not show mitotic acitivity or a tendency for neoplastic transformation. To determine the histogenesis of these foci, extensive immunocytochemical reactions were carried out with antibodies to a variety of glial, neuronal and nonneural cell lineages. With the exception of S-100 protein, no immunoreactivity was detectable. S-100 was consistently expressed in these foci, irrespective of their size, location, and degree of polymorphism. On the basis of cytological appearance, distribution and immunoreactivity we tentatively designate these foci as glial micro-hamartomas. Although we did not systematically analyze the CNS of patients with von Recklinghausen neurofibromatosis (neurofibromatosis 1, NF1), the present study strongly suggests that these micro-hamartomas constitute a morphological hallmark of bilateral acoustic neurofibromatosis (NF2).
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  • 83
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    Acta neuropathologica 79 (1989), S. 149-153 
    ISSN: 1432-0533
    Keywords: Lead ; Rat ; Cerebellum ; Particle-induced X-ray emission (micro-PIXE)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The distribution of lead in the cerebellum of suckling Sprague-Dawley rats was examined using a nuclear microprobe for elemental mapping of tissue sections (particle-induced X-ray emission, 3-μm beam of 2.5 MeV protons; micro-PIXE). The rats were injected intraperitoneally with a lead-containing vehicle or vehicle only from ages 1 to 14 days. The calculated doses were 7.8 (low-dose) and 15.6 (high-dose) μg lead/g body weight. The rats were killed at 20 days of age. The vascular system was rinsed quickly with 0.15 M ammonium acetate to obtain determinations of intra-parenchymal lead with minimal influence of lead bound to erythrocytes and plasma proteins. Brains were frozen in propane/propylene in liquid nitrogen. Cryostat sections, 15 μm thick, were air dried on formvar coats that covered a hole, 15 mm in diameter, in a plastic disc, and were used for lead analysis by micro-PIXE. Very low concentrations of lead were found in the brain of controls. Lead levels in homogenates from cerebrum and cerebellum measured by atomic absorption spectrometry (AAS) were: low-dose 1.2–2.2 μg/g wet weight and high-dose 1.4–2.4 μg/g wet weight. The lead levels measured with the micro-PIXE method were in good agreement with the levels found with AAS. Lead was present in the cerebellar white matter in two to three times higher amounts than in the cortical grey (low-dose white matter 11–18 μg/g dry weight, grey matter 2.0–5.5 μg/g dry weight). This was true for both low and high dose exposed rats. Lead concentrations in rats subjected the high-dose lead exposure were approximately 60% higher than those in low-dose exposed rats. Concentrations were lower in the Purkinje cell layer than in other parts of the cortex. These new findings on the distribution of lead in suckling rats are discussed in relation to the pathogenesis of experimental lead encephalopathy.
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    Acta neuropathologica 78 (1989), S. 159-165 
    ISSN: 1432-0533
    Keywords: Encephalitis ; Encephalomyelitis ; Immunohistochemistry ; Pathogenesis ; Rabies
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The spread of rabies virus in the central nervous system of mice was examined after hindlimb footpad and intracerebral inoculation of the CVS strain of fixed rabies virus. All mice developed paralytic rabies. After intracerebral inoculation there was early simultaneous infection of neurons in the cerebral cortex and pyramidal neurons of the hippocampus, and later there was spread to the cerebellum. After high-dose intracerebral inoculation there was early infection ependymal cells lining the lateral ventricles and neurons adjacent to the central canal of the spinal cord, suggesting that rabies virus entry into the CNS occurs, at least in part, by a cerebrospinal fluid pathway. The sequence of involvement was different after hindlimb footpad inoculation. Infection became established in the cerebellum on day 5, in the cerebral cortex on day 6, and in the hippocampus on day 8. CA3 was initially affected, CA1 became infected 2 days later, and there was much less involvement of the dentate gyrus. Hippocampal infection occurred late relative to the rest of the brain after peripheral inoculation, but not after intracerebral inoculation. The hippocampus is not a good location for the detection of early brain infection after peripheral inoculation, although it may be involved when a natural rabies vector has the ability to transmit infection. These findings also raise questions about the mechanisms for the limbic dysfunction observed in clinical rabies.
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  • 85
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    Acta neuropathologica 78 (1989), S. 258-263 
    ISSN: 1432-0533
    Keywords: Teratoma ; Microglia ; Nervous tissue ; Immunohistochemistry ; Tumor markers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Ten human teratomas arising outside the central nervous system (CNS) were studied using a panel of immunohistochemical, and lectin histochemical stains to determine the relationship of the presence of microglia to markers of neural maturity or differentiation. Microglia, identified by silver carbonate,Ricinus communis agglutinin-1 (RCA-1), or both were found in eight out of ten cases. They were common in mature areas which also had S-100, glial fibrillary acidic protein, vimentin, neurofilament, and synaptophysin immunostaining. Microglia were distinguished from macrophages in necrotic foci. Cells which were RCA-1 positive and silver carbonate positive were found in immature neural tissues but these lacked all typical features of microglia. These observations indicate that true microglia are frequent in nonCNS teratomas and that they are found in association with other indicators of neural maturation. The presence of possible precursors in immature areas suggests that microglia undergo maturation concurrent with neural differentiation in these tumors.
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    Acta neuropathologica 78 (1989), S. 264-269 
    ISSN: 1432-0533
    Keywords: Skeletal muscle ; Regeneration ; Growth factors ; Growth hormone ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Against the background of the importance of growth hormone (GH) for normal muscle growth, a study was performed to investigate whether lack of GH after hypophysectomy affects the cell proliferation and the local production of insulin-like growth factor-I (IGF-I) in the early stages of muscle regeneration in adult rats. The level of IGF-I in the serum of hypophysectomised rats was reduced to about 30% of that of controls. The incorporation of [methyl-3H]thymidine into the regenerating muscle showed a peak 6 days after the operation and then gradually declined to the end of the period of study 30 days after initiation of regeneration by ischemic necrosis. The DNA content rose to a maximum level after 6–8 days, and remained high after 30 days. There was no major difference in the incorporation of [3H]thymidine in regenerating muscle of hypophysectomised and control rats, but the DNA concentration in the regenerating muscles of hypophysectomised rats was significantly reduced after 30 days. There was a corresponding reduction in the number of nuclei per muscle fibre, indicating that hypophysectomy has a small effect on the cell proliferation during the early stages of muscle regeneration. Immunohistochemical demonstration of IGF-I in the regenerating muscle revealed the transient presence of immunoreactive material in satellite cells and myotubes after 6 to 8 days of regeneration but no immunoreactivity after 30 days. No obvious difference was observed between hypophysectomised and control rats, indicating that the endogenous production of IGF-I in regenerating skeletal muscle can occur independently of GH.
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  • 87
    ISSN: 1432-0533
    Keywords: Glial fibrillary acidic protein ; Vimentin ; Immunohistochemistry ; Ethylnitrosourea ; Rat Gliomas
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The expression of glial fibrillary acidic protein (GFAP) and vimentin was investigated immuno-histochemically in 104 experimental gliomas induced by transplancental application of ethylnitrosourea (ENU) in CDF rats. Immunoreactivity for vimentin was prominent in many astrocytic tumor cells and especially in small glioma cells forming anaplastic medulloblastoma-like foci in many tumors. The majority of tumor cells in oligodendroglial tumors were vimentin negative, except for some of the large polymorphous oligodendrogliomas which contained intermingled vimentin positive glioma cells. GFAP immunoreactivity was detectable only in a low fraction of tumor astrocytes and in a few exceptional cases some oligodendroglial tumor cells stained positive. Immunohistochemistry with antibodies against neurofilaments and cytokeratins revealed no staining in tumor cells of ENU-induced gliomas, while all oligoden-drogliomatous tumors stained positive for HNK-1. Immunocytological and immunoblot investigations of the two rat glioma cell clones RG2 and F98, which are both derived from ENU-induced gliomas, showed a prominent expression of vimentin in monolayer cultures and in syngeneic intracerebral transplantation tumors. F98 additionally demonstrated a fraction of GFAP positive cells especially in confluent cultures and in intracerebral tumors. RG2, on the other hand, exhibited virtually no GFAP immunoreactivity in culture but showed individual GFAP positive tumor cells in intracerebral tumors. Our results revealed a more precise picture of the cellular differentiation in ENU-induced rat gliomas and in two widely used glioma cell lines. They underline the heterogeneity of experimental rat gliomas which may comprise cells at different stages of differentiation towards the oligodendroglial or astroglial phenotype.
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  • 88
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    Acta neuropathologica 78 (1989), S. 325-328 
    ISSN: 1432-0533
    Keywords: Ependyma ; Ependymoma ; Epithelial membrane antigen ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The ependyma and choroid plexus of 23 normal brains and 20 ependymal tumors were examined immunohistochemically for expression of epithelial membrane antigen (EMA) using a specific monoclonal antibody. The ependyma of normal brains showed three patterns of immunoreactivity: membrane immunoreactivity confined to the luminal surface; irregular punctate intracytoplasmic immunore-activity in the subependymal layer; and spherical and ring-like intracytoplasmic immunoreactivity in the subependymal layer. Of 13 differentiated ependymomas 11 reflected the immunoreactive patterns of normal ependyma. The anaplastic ependymomas and ependymoblastomas had no immunoreactivity. Our results indicate that EMA has a highly selective distribution in the ependyma, and is a marker for differentiated ependymoma.
    Type of Medium: Electronic Resource
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  • 89
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    Acta neuropathologica 78 (1989), S. 472-483 
    ISSN: 1432-0533
    Keywords: Astroblastoma ; Electron microscopy ; Immunohistochemistry ; Organ culture ; Tanycytes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Two examples of cerebral astroblastoma have been studied by electron microscopy and immunohistochemistry, one of them having been maintained in vitro in an organ-culture matrix system for 8 months and the explants studied by light and electron microscopy at different time intervals. The fine structural characteristics were those of a glial cell type with features intermediary between those of astrocytes and ependymocytes. They recapitulated the structure of the tanycyte, a glial precursor cell which is normally found scattered along the ependymal lining of the embryonal and neonatal mammalian brain, but is distinct from epithelial ependymocytes. The possible origin of some astroblastomas from such a cell would account for a number of characteristics in this enigmatic type of glioma.
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  • 90
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    Acta neuropathologica 77 (1989), S. 445-448 
    ISSN: 1432-0533
    Keywords: Ectopic meningioma ; Immunohistochemistry ; Pathogenesis ; Electron microcopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Peripheral nerve meningiomas are exceedingly rare neoplasms of controversial origin; only four cases have been reported. Proposed origins of ectopic meningiomas include extradural trapping of arachnoid cells during embryogenesis, ectopic migration of arachnoid cell nests with the developing peripheral nerve, and metaplasia of mature peripheral nerve sheath cells or a common progenitor cell. In this report of a meningioma of the brachial plexus, immunohistochemical and ultrastructural examinations of the tumor matched all the criteria of a traditional meningioma but failed to clarify the origins of such neoplasms.
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  • 91
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    Acta neuropathologica 79 (1989), S. 27-29 
    ISSN: 1432-0533
    Keywords: Malignant lymphoma ; Non-Hodgkin lymphoma ; Brain tumor ; Tumor-infiltrating lymphocyte ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary An immunohistochemical study was performed on small lymphoid cells present in frozen tissue sections of seven cases of primary B cell malignant lymphomas of the brain by using monoclonal antibodies to T cell (Leu-1, OKT-11, Leu-3a, and Leu-2a) and B cell (BA-1 and Leu-12) surface markers. In all the seven cases, positive reaction for Leu-1 and OKT-11 was seen in the majority of the small lymphoid cells which were dispersed among the lymphoma cells or clustered around blood vessles. The large neoplastic cells were unstained by these antibodies. Staining for T cell subsets with antibodies to Leu-3a and Leu-2a showed heterogeneous staining in each case. The ratio of Leu-3a+ to Leu-2a+ cells was less than one in six cases, demonstrating a suppressor/cytotoxic phenotype predominance. Most of these small lymphoid cells were negatively stained by antibodies to BA-1 and Leu-12. From these findings, it was shown that the small lymphoid cells observed in primary B cell lymphomas of the brain were of T cell lineage, distinct from the neoplastic cells, and probably reactive in nature. The implications of these findings are discussed.
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  • 92
    ISSN: 1432-0533
    Keywords: Amyotrophic lateral sclerosis ; Phosphorylated neurofilament ; Immunohistochemistry ; Lewy body-like inclusion ; Cord-like neurite thickening
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Distribution of phosphorylated neurofilament proteins within anterior horn cells in three cases of familial and six cases of sporadic amyotrophic lateral sclerosis (ALS) and ten control cases were investigated by using a monoclonal antibody. Two distinct staining patterns of perikarya were observed; (1) homogeneous pattern; either the entire or a part of the perikaryon was immunostained homogeneously (homogeneously diffuse or partial pattern); (2) focal pattern: perikarya contained very distinct, inclusion-like focal accumulation of immunoreactive products of various morphologies such as round, ring-shaped, cord-like, tube-like and more irregular shapes. The homogeneous pattern was found in all three groups but was most common in sporadic ALS. On the other hand, the focal pattern was seen almost exclusively in familial ALS. The focal accumulation of neurofilaments appears at least in part to be related to the Lewy body-like hyaline inclusion which is known to contain neurofilaments. In addition, cord-like swellings of neurites in familial ALS also showed focal neurofilament accumulation. These observations suggest that the focal accumulation of phosphorylated neurofilaments is characteristic of familial ALS, although it may not be specific to the entity. The pathological process(es) producing the neurofilamentous abnormality may play an important role in anterior horn cell degeneration in familial ALS.
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  • 93
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    Acta neuropathologica 77 (1989), S. 654-658 
    ISSN: 1432-0533
    Keywords: Melanotic neuroectodermal tumor ; Immunohistochemistry ; Ultrastructure ; Pineal origin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A case of a melanotic neuroectodermal tumor arising from pineal region of a 4-year-old girl is presented. The tumor had spread diffusely to the meninges, consistent with malignant behavior. Histologically, the tumor consisted primarily of epithelial elements arranged in tubules, cords and nests separated by fibrous vascular tissue in addition to a small neuroblastomatous focus. Melanin pigment was frequently observed in the epithelial tumor cells, and melanin-laden macrophages were also often observed. No teratoid elements were found. Immunohistochemically, tumor cells were positive for neuron-specific enolase but were nonreactive for S-100 protein, epithelial membrane antigen, glial fibrillary acidic protein, vimentin, α-fetoprotein and human chorionic gonadotrophin. Ultrastructurally, the epithelial nature of the tumor cells could be easily demonstrated. In addition, melanosomes in various stages in maturation were observed, indicating melanogenesis of the tumor. On the basis of the tumor location and the histological similarities previously observed for the fetal pineal body, it is very likely that this melanotic epithelial tumor could have originated from the fetal pineal gland.
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  • 94
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    Acta neuropathologica 78 (1989), S. 65-71 
    ISSN: 1432-0533
    Keywords: Striatonigral degeneration ; Basal ganglia ; Calcineurin ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The basal ganglia (including substantia nigra) of two patients with striatonigral degeneration, who had clinical histories of Parkinson's disease, were studied immunohistochemically using a purified antibody to calcineurin (CaN). Marked loss of CaN-immunoreactive neurons in the putamen and neuromelanin-pigmented neurons in the zona compacta of the substantia nigra was seen in both cases. A small number of CaN-immunoreactive neurons remained dispersed in “clusters” or “islands” in the medial portion of the putamen. In one case there was loss of CaN-immunoreactive neurons in the caudate nucleus to a lesser degree than that in the putamen. In addition, both cases showed marked depletion of CaN-immunoreactive afferent nerve fibers in the external and internal segments of the globus pallidus and the zona reticulata of the substantia nigra. This report emphasizes the usefulness of the CaN-immunostaining technique for assessing the striatal efferents in human basal ganglia, and shows the neuropathological changes in the basal ganglia with striatonigral degeneration which were not possible to ascertain with previous techniques.
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  • 95
    ISSN: 1432-0533
    Keywords: Immunohistochemistry ; Medulloepithelioma ; Cytoskeletal proteins
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Four examples of human cerebral medulloepithelioma were studied immunohistochemically with a panel of antibodies and antisera to neuronal and glial proteins. The tumors, in addition to primitive medullary epithelium, contained areas of neuroblastic, ganglionic, astrocytic, ependymoblastic and ependymal differentiation, and, in one tumor, areas resembling polar spongioblastoma. Tumor cells throughout the primitive medullary epithelium displayed focal immunocreactivity for vimentin, glial fibrillary acidic (GFA) protein and for the neuron-associated class III β-tubulin isotype. Neuroblasts showed immunoreactivity for the class III β-tubulin isotype, microtubule-associated protein 2 and neuron-specific enolase. Immunoreactivity for neurofilament epitopes and synaptophysin was detected in areas of ganglionic differentiation and coincided with the demonstration of neurofibrils in Bielschowsky's silver impregnations. Vimentin was the only marker detected in ependymoblastic and ependymal rosettes or in areas of polar spongioblastoma, as well as in mesenchymal, cells. The results indicate that, even in very primitive neoplastic neuroepithelium, immunocytochemical evidence of early commitment of some of the cells to a neuronal or glial lineage can be demonstrated. The neuron-associated class III β-tubulin isotype appears to be one of the earliest markers indicative of neuronal differentiation in normal and neoplastic primitive neuroepithelium.
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  • 96
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    Acta neuropathologica 79 (1989), S. 305-309 
    ISSN: 1432-0533
    Keywords: Gliosarcoma ; Immunohistochemistry ; Histiocyte
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Gliosarcomas contain both neuro-ectodermal and mesenchymal elements. Its histogenesis has been much debated and endothelial and adventitial fibroblast origins have been suggested, as has a “histiocytic” origin following the demonstration of antiprotease activity. Eight gliosarcomas have been examined with a panel of ten monoclonal and polyclonal antibodies to investigate the origin of the sarcomatous element. Glial fibrillary acid protein expression showed a sharp distinction between gliomatous and sarcomatous tumour components. Contrary to some previous reports factor 8-related antigen and Ulex europeus agglutinin stained vascular luminal endothelium but no tumour cells. Vimentin and fibronectin expression was extensive and confined largely to sarcomatous areas. Desmin and neurofilament protein could not be demonstrated in any of the cases. Numerous cells, particularly in the sarcoma areas, expressed alpha-1-antitrypsin and-chymotrypsin. A proportion of these stained for the monocyte/macrophage marker MAC 387. Four cases focally exhibited a true stori-form pattern and this and the immunohistochemical results suggest analogies with the fibrous histiocytomas. These tumours contain reactive histiocytes but are now thought to be derived from fibroblasts or from pluripotent mesenchymal cells in perivascular adventitia. This resembles the pattern exhibited in the sarcomatous component of gliosarcomas.
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  • 97
    ISSN: 1432-0533
    Keywords: Protein kinase C ; Proliferative activity ; Immunohistochemistry ; Human brain neoplasms
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Protein kinase C (PKC), the major receptor for phorbol ester tumor promotors, is a phospholipid- and calcium-dependent phosphorylating enzyme which plays an important role in the intracellular signal transduction necessary for a variety of basic cellular functions including the control of cell proliferation. To determine the expression of PKC in human neurogenic tumors we investigated 121 tumors of the human nervous system by means of immunohistochemistry using the monoclonal antibody C5. The results were compared with immunohistochemical staining for intermediate filament proteins, desmoplakins, and the proliferation-associated nuclear antigen Ki-67. Besides strong staining of normal and reactive astrocytes, C5 immunoreactivity was consistently observed in tumor cells of all types of gliomas. However, the fraction of C5 positive tumor cells varied between the different tumor types with astrocytomas and subependymomas demonstrating the strongest immunoreactivity. In the other gliomas, especially those of higher malignancy, a considerable heterogeneity in C5 expression could be observed. There was a tendency for the percentage of C5 immunostained tumor cells being lower in high-grade gliomas compared to low-grade ones and comparison with Ki-67 staining frequently revealed an inverse relationship between proliferative activity and C5 immunoreactivity. Besides the gliomas we found 3 of 7 neurinomas and 6 of 18 meningiomas which were partially C5 positive. All other tumors investigated including medulloblastomas and metastatic carcinomas were C5 negative. Our results thus indicate that immunohistochemistry for PKC using the monoclonal antibody C5 could be an useful aid for histopathological tumor classification in neurooncology.
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  • 98
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    Acta neuropathologica 78 (1989), S. 332-335 
    ISSN: 1432-0533
    Keywords: Gliosarcoma ; Subependymoma ; Immunohistochemistry ; Factor VIII-related antigen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A case of a recurrent posterior fossa subependymoma in a 60-year-old man is reported. In the recurrent tumor, the vasculature had undergone apparent sarcomatous proliferation of the endothelial cells. The bizarre cells expanded and replaced the vessel walls, and stained for Factor VIII-related antigen. The literature on gliosarcomas arising in brain tumors other than high-grade gliomas is reviewed.
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  • 99
    ISSN: 1432-0533
    Keywords: Somatostatin ; Immunohistochemistry ; Aganglionosis ; Man ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The distribution of somatostatin-like immunoreactive (SOM-LI) nerves was elucidated immunohistochemically in the gut tissues from patients with Hirschsprung's disease and congenital aganglionosis rats. In the normoganglionic human colon, SOM-LI nerve cell bodies were found to a greater extent in the submucous plexus and to a lesser extent in the myenteric plexus. However, they were rarely observed in both the plexuses of the oligoganglionic segment. SOM-LI nerve fibres were widely distributed in the aganglionic bowel. The circular muscle layer of the distal aganglionic segment was densely innervated by SOM-LI nerve fibres which are probably derived from the extrinsic, hypertrophic nerve bundles. A decreased number of the intramuscular nerves fibres were seen in the proximal aganglionic segment. In the colon and rectum from adult and 21-day-old rats, SOM-LI cell bodies were numerous in both plexuses. On the other hand, enteric neurons were completely lacking from the colon and rectum of congenital aganglionosis rats of 21 days old. No neuronal elements staining for SOM were disclosed in these aganglionic segments of mutant rats. A possible origin and pathophysiological role of the extrinsic nerve fibres containing SOM in the diseased bowel are discussed. It is concluded that SOM-LI nerves in the human distal colon comprise both intrinsic and extrinsic elements, while SOM nerves in the rat colon and rectum are of only intrinsic origin.
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  • 100
    ISSN: 1432-0533
    Keywords: Globus pallidus ; Immunohistochemistry ; Calcineurin ; Synaptophysin ; Neuropeptides
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The afferent nerve terminal in the human globus pallidus, which receives the projection nerve fibers from both the striatum and the subthalamic nucleus, were clearly visualized immunohistochemically using antibodies to calcineurin, synaptophysin, Met-enkephalin (MEnk) and substance P (SP). In normal control case, MEnk and SP-like immunoreactivities were densely localized in the external and internal pallidal segments, respectively, whereas calcineurin and synaptophysin were distributed throughout the globus pallidus. Calcineurin, synaptophysin, MEnk and SP-like immunoreactive peroxidase products decorated most of the long radiating dendrites and the cell bodies of the pallidal neurons. In the cases with Huntington's disease (HD) and striatonigral degeneration (SND), marked loss of calcineurin, MEnk and SP-like immunoreactivities was seen in the globus pallidus corresponding to areas of striatal neurodegeneration, whereas synaptophysin immunoreactivity remained in areas which revealed almost complete loss of calcineurin, MEnk and SP-like immunoreactivities. Calcineurin, MEnk and SP, which show difference in their localization patterns, may provide reliable markers for the striatal efferent nerve terminals, and synaptophysin for the entire pallidal afferent nerve terminals. This report demonstrates the distribution patterns of these neurochemical molecules in the globus pallidus with HD and SND.
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