Immunohistochemical evidence of thiol-protein disulfide oxidoreductase (TPO) in neurosecretory nerve cells of different vertebrates.
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Biomedical subjects
Publications and source records attributed to H G Bernstein.
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Ornithine decarboxylase was localized immunohistochemically in paraffin sections of prostate glands of the rat using Sternberger's PAP technique. Two types of immunoreactive cells were detected in the gland epithelium: strongly positive ones and weakly positive ones. Unreactive cells were also present. The functional role of the enzyme in the secretory process of the glands is discussed in the light of these findings.
The regional distribution and cellular localization of cathepsin D immunoreactivity was demonstrated at the light microscopic level in the CNS of rat and man by use of unlabelled immunoenzyme technique. A wide but uneven distribution was substantiated for the rat brain. Furthermore, we present evidence that antiserum produced against rat liver enzyme is capable of recognizing cathepsin D in human brain.
A nonchromaffin paraganglioma was found in the periglandular connective tissue of the glandula suprarenalis of a sheep-dog bastard and characterized by histological and immunohistochemical techniques. Insulin-, glucagon- and gastrin/cholecystokinin-like material was revealed within the cells of the tumour. Possible functional consequences of these findings are discussed.
Samples of cerebrospinal fluid were taken from 81 patients and investigated for insulin-like immunoreactivity by use of radioimmunoassay. The data suggest that IRI levels of Liquor cerebrospinalis are independent of blood insulin concentrations. It is supposed that nervous tissue is the source of IRI in the cerebrospinal fluid.
The cellular localization and regional distribution of peptides of the gastrin/cholecystokinin family was investigated in human fetal, neonatal and adult brains by use of immunohistochemical techniques. It could be revealed that a cholecystokinin-like immunoreactivity is already present in human brain at the 11/12th gestational weeks. With the 19th week a strong increase in number of CCK reactive cells and the reaction intensity is obvious. The data are compared with the distribution pattern of the adult brain. Our data permit to conclude that gastrin/CCK-related material might play roles independent of neurotransmitter functions during early human brain development.
Immunohistochemical and histological investigations were undertaken on 24 surgically-removed pituitary adenomas. By histology (haemalu-eosin staining), 7 chromophobe, 12 acidophil and 5 basophil pituitary adenomas were revealed. For immunohistochemical purposes the peroxidase-antiperoxidase technique was applied. Primary antisera against 10 hormones were used. By immunohistochemistry, 7 prolactin-containing, 2 TSH-containing, 2 GH-containing and 1 beta-endorphin-containing pituitary adenomas were identified. Furthermore, 1 mixed thyrotropic-prolactin human pituitary adenoma was detected. A possible connection between histological and immunocytochemical findings is discussed.
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By use of a specific antiserum against the insect peptide proctolin we were able to identify proctolin-immunoreactive neurons in the mouse brain. These nerve cells belong to the nuc. mesencephalicus n. trigemini. Furthermore, the antiserum stained very few nerve fibers with varicosities in the immediate neighborhood of the roof of the third ventricle. The chemical identity of the immunoreactive material with genuine proctolin remains to be elucidated.
We studied the behavior of the insulin-like immunoreactivity in brains of rats and mice during the first 20 d post natum by immunohistochemistry and radioimmunoassay. It was found that a dramatic decline in the concentration of the peptide, accompanied by a strong reduction of immunoreactive cells, takes place during this period. A possible role of cerebral insulin as a promoter of nerve cell growth and development is briefly discussed.
The immunohistochemical localization of insulin/insulin-like immunoreactivity in different regions of the human brain was reevaluated by use of monoclonal antibodies against insulin. The data obtained support our earlier findings that cerebral insulin is present in nerve cells of several brain areas.
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Gastrin/CCK immunoreactivity appears to be widely distributed throughout the mammalian CNS, being most abundant in the cerebral cortex [Vanderhaeghen et al. 1975; Straus et al. 1977; Beinfeld et al. 1981]. Besides its putative role as a co-transmitter in dopaminergic neurotransmission [Hökfelt et al. 1980], cholecystokinin is apparently involved in the central regulation of appetite and satiety [Gibbs et al. 1973; Antin et al. 1975; Parret and Batt 1980; Smith 1980; Smith and Gibbs 1981] Furthermore, it has been shown that the brain concentration of the peptide is decreased in genetically obese mice as compared to non-obese animals [Strauss and Yalow 1979]. The sand rat (Psammomys obesus) is a desert rodent which tends to become diabetic when it is fed with normocaloric diet and restricted in movement [Haines et al. 1965; Hahn et al. 1971]. However, the usefulness of this animal as a paradigm of diabetes is now being revised, since because in its typical expression this metabolic dysfunction appears to be an obesity syndrome [Rice and Robertson 1980]. Therefore, it seems to be necessary to study the distribution of gastrin/CCK-immunoreactive nerve cells in the brain of normal and diabetic (obese) sand rats to get further information about mechanism underlying the development of this form of diabetes.
The regional distribution and the cellular localization of insulin-immunoreactive material in the rat brain has been studied during postnatal ontogenesis by use of radioimmunoassay and immunocytochemistry. It could be shown that there is a decrease in the amount of the peptide in the rat brain during postnatal maturation of the organ. This decline in insulin concentration is morphologically evident by a strong reduction of insulin positive nerve cells. Our findings support the hypothesis that insulin might play important roles as a nerve growth-promoting factor.
The cellular localization and regional distribution of "insulin-like immunoreactivity" and "C-peptide immunoreactivity" were studied in brains of fetuses and newborns from normoglycaemic and diabetic mothers using immunohistochemical techniques. It is shown that "insulin-like material" and "C-peptide-like material" occur in the same nerve cells. No differences in regard to the localization of both polypeptides exist between abort material from normoglycaemic and diabetic mothers.
Glucagon-like peptides in the central nervous system (CNS) of man with the immunofluorescence and the peroxidase-antiperoxidase method were studied. It has been found that there are immunoreactive glucagon cells present in the hypothalamus hippocampus, amygdaloid nuclei cerebral cortex, and medulla oblongata region. The findings confirm earlier investigations from this laboratory performed along this line.
The cellular localization and regional distribution of insulin- and glucagonlike substance, C-peptide-like immunoreactivity, thiol:protein disulphide oxidoreductase, TPO (E.C.1.8.4.2.), and insulin/glucagon-specific proteinase, ISP (E.C.3.4.22.-), are studied in the CNS of man, adult and juvenile rats, mice, tortoises, and frogs by use of immunohistochemistry. Furthermore, the content of immunoreactive insulin, glucagon, and C-peptide was estimated in human cadaver brains by radioimmunoassay. It could be shown that insulinlike immunoreactive material is widely distributed in the human brain and the CNS of juvenile rats as well as in mice, whereas in the CNS of adult rats and nonmammalian animals (frogs, tortoises) the polypeptide is restricted to a few nerve cell populations. C-peptide immunoreactivity was demonstrated in human CNS in the same nerve cells as insulin. By use of two different glucagon-antisera it was revealed that gut-type glucagon occurs in many nerve cells of human and mouse brains, as well as in the CNS of juvenile rats. On the other hand, pancreas-type glucagon was less widely distributed in the human brain and nearly not detectable in the CNS of mice and rats. With the exception of neurosecretory nerve cells, there was a high degree of coincidence between the localization of insulin and TPO. The immunoreaction against the ISP antiserum was weak, but correlated well with the distribution of insulin-immunoreactivity. The occurrence of TPO and ISP in the brain demonstrates the ability of nervous tissue to degrade insulin and glucagon. By radioimmunoassay it was established that human brain contains insulin, glucagon and C-peptide at concentrations that exceed blood levels. We conclude from our data that, at least in part, cerebral insulin and glucagon are products of the brain itself.
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