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Biomedical subjects

S Falkmer

Publications and source records attributed to S Falkmer.

At least 109 records · Page 6Linked to original sources

Blood glutathione in various phases of insulin-dependent diabetes mellitus in children.

Reduced glutathione (GSH) in whole blood was studied in 15 insulin-dependent juvenile diabetic patients at onset of diabetes (group A). In 5 of these patients the blood GSH concentration was followed during the first month after onset. The blood GSH content was also analyzed in 16 children with insulin-dependent diabetes mellitus (IDDM) with a duration of diabetes of more than 2 years (group B), and in a control group of 76 healthy children (group C). The GSH levels in groups A, B and C were 48.3 +/- 5.7, 47.1 +/- 4.6 and 47.6 +/- 4.3 mg/100 ml erythrocytes, respectively. Thus, there were no significant differences between the patients and the control group. In group A, there were no significant differences in blood GSH values at onset and 1 month later.

Adolescent↗

Immunohistochemical, morphometric, and clinical studies of the pancreatic islets in infants with persistent neonatal hypoglycemia of familial type with hyperinsulinism and nesidioblastosis.

A new era has been started in the morphological research of the human pancreatic islet parenchyma by the introduction of immunohistochemical (IHC) and modern morphometric techniques. This statement is illustrated by a report of two infants from two families with persistent neonatal hypoglycemia with hyperinsulinism, where specimens of pancreas, obtained at subtotal pancreatectomy, were analyzed together with autopsy specimens from age-matched "controls" (cardiac malformations). It was found that a nesidioblastosis-like picture occurred in the pancreas of the "controls", at least up to 6-7 months of age, and that in IHC stained sections this was indistinguishable from that observed in the endocrine pancreas of the hypoglycemic infants. Moreover, there was no difference in the total volume density of the islet parenchyma in pancreas of controls and hypoglycemic children when analyzed by morphometry. However, an increase in the relative incidence of insulin cells was found in the hypoglycemic infants as well as a moderate reduction of glucagon cells and a marked decrease of somatostatin cells. Clinically, some alleviation of the symptoms could be obtained by administration of glucagon and somatostatin, indicating that the hypothesis is correct that a defect in the maturation of the islet parenchyma during infancy may be a main pathogenetic factor in the syndrome. The familial occurrence of the disease may be more common than previously realized.

Blood Glucose↗

Occurrence of neurotensin-immunoreactive cells in the digestive tract of lower vertebrates and deuterostomian invertebrates. A correlated immunohistochemical and radioimmunochemical study.

In the mucosal epithelium of the digestive tract of two marine teleost bony fish, one cartilaginous fish, one cyclostome, and in that of two of three representatives of deuterostomian invertebrates studied, endocrine cells of open type were found, exhibiting immunoreactivity with antisera against C-terminal sequences of mammalian neurotensin and of the structurally closely related amphibian neurohormonal peptide xenopsin. From these observations, and from those of previous studies, it is suggested that neurotensin cells do not occur in the digestive tract mucosa until at the evolutionary level of the more highly developed deutoerostomian invertebrates. Three evolutionary stages seem to exist in the distribution pattern. The first stage, characterized by few, widely scattered cells, is found in the uro- and cephalochordates, the cyclostomes, the cartilaginous fish, and the stomachless bony fish. In the second stage, comprising the remaining submammalian classes, including more highly developed bony fish, the typical distribution pattern is that of numerous neurotensin immunoreactive cells in the antrum, pylorus, and duodenum. The final stage of neurotensin evolution is found in higher mammals and is characterized by a great density of neurotensin immunoreactive cells in the ileum.

Animals↗

Immunohistochemical evidence of gastro-entero-pancreatic neurohormonal peptides of vertebrate type in the nervous system of the larva of a dipteran insect, the hoverfly, Eristalis aeneus.

Using rabbit and guinea-pig antisera, raised against GEP neurohormonal peptides of mammalian origin, cells were observed in the brain and/or in the fused ventral ganglia of the last (fifth) larval instar of the hoverfly, Eristalis aeneus, being immunoreactive with antisera against insulin, somatostatin, glucagon, PP, secretin, gastrin/CCK/caerulein; substance P, enkephalin and endorphin. Most of these GEP neurohormonal peptides also occurred in nerve fibers. No immunoreactive cells or nerve fibers could be detected with antisera against GIP, VIP, (the central fragments of) CCK, bombesin or neurotensin. The antisera tested failed to reveal any immunoreactive cells or nerves in Weismann's ring (fused corpus allatum/corpus cardiacum and thoracic gland) or in different parts of the alimentary tract. The observations support the hypothesis that neuronal GEP hormonal peptide production in the brain is a genuinely original mechanism and the appearance of endocrine cells in the gut a later feature in evolution.

Animals↗

Immunocytochemical demonstration of enkephalin and beta-endorphin in endocrine tumors of the rectum. A survey of 27 colo-rectal carcinoids.

In a histopathological and immunocytochemical study of biopsy and/or operation specimens from 27 patients with endocrine tumors of the colon and rectum ("hind-gut carcinoids") enkephalin-immunoreactive tumor cells were observed in two cases. Both patients were obese women, about 50 years of age, with a history of constipation. The tumors were situated near the anus in the dorsal wall of the rectum. One tumor had metastasized to a lymph node, and the other showed vascular invasion. The tumor cells were non-argentaffin; some were argyrophil. One tumor contained only few enkephalin-immunoreactive cells but had numerous beta-endorphin-immunoreactive cells, which were distinct from the former. The other contained large numbers of enkephalin-immunoreactive cells but no beta-endorphin cells. Both tumors also harboured glucagon-immunoreactive cells; in one there were also cells containing immunoreactive pancreatic polypeptide. These cells were distinct from the enkephalin-storing ones. No 5-hydroxytryptamine could be detected in the two tumors.

Colonic Neoplasms↗

Vasoactive intestinal polypeptide (VIP) in epithelial cells of the gut mucosa of an elasmobranchian cartilaginous fish, the ray.

As part of study of the phylogeny of VIP, it was observed that the colonic mucosa of the cartilaginous fish, Raja radiata and Raja clavata, contained numerous epithelial cells, obviously of closed type, displaying intense VIP immunoreactivity. Accordingly, high concentrations of VIP were found by radioimmunoassay. At the ultrastructural level, the VIP cells were characterized by the presence of highly electron dense secretory granules. The colonic mucosa of the ray may be a good source for the isolation of an early VIP.

Animals↗

Immunocytochemical studies of the evolution of islet hormones.

By using both immunofluorescence and peroxidase-anti-peroxidase procedures to detect cells producing the four islet hormones, supplemented by biochemical, biological, and radioimmunological assays of tissue extracts, it has been shown that insulin seems to be the most original hormone, apparently occurring already in invertebrates in cells of open type in the alimentary tract mucosa. Insulin cells also predominate in the first islet organ, namely that of the cyclostomes. The order of appearance in the endocrine pancreas during the subsequent evolution is: somatostatin; glucagon; and the pancreatic polypeptide. Even in lower vertebrates pancreatic polypeptide cells occur in those parts of the pancreas situated in close proximity to the gut.

Animals↗

Hepatomas and other neoplasms in the atlantic hagfish (Myxine glutinosa): a histopathologic and chemical study.

M. glutinosa is a cyclostome, living in the mud in seawater of high salinity. It probably is a stationary scavenger feeder. About 28,000 hagfish from the Gullmar Fjord were examined during a 5-year period for the occurrence of tumors. Hepatomas were found to be predominant neoplasm, observed at a frequency that decreased from 5.8% in 1972 to 2.9% in 1973 and finally to 0.6% in 1974--76. Islet cell hamartomas and frank neoplasms decreased from 0.5% in 1972 to less than 0.1% in 1973--76. Occasional subcutaneous and mesenterial neoplasms were also observed during 1972--74. In hagfish caught 12 km out in the open sea, the hepatoma incidence decreased from 2.8% in 1972 to 0.9% in 1974. Given this background, it is possible that pollution of the Gullmar Fjord by carcinogenic substances with low biodegradability has occurred until 1972, and this pollution could be of etiologic significance for these hagfish tumors. In fact, the use of PCBs became prohibited by law in Sweden in 1971--72. Severe restrictions were also introduced for the use of chlorinated pesticides, notably DDT, and associated substances (DDD, DDE). Preliminary analyses for the presence of PCBs, DDT (and its metabolites), and aflatoxins (the notorious hepatocarcinogen) were performed by gas chromatography and thin-layer chromatography. Livers (with and without neoplasms) from hagfish caught inside the threshold of the fjord contained about 5 mg/kg of wet weight of PCBs and about 0.1--0.4 mg/kg of dry weight of DDT, DDD, or DDE, whereas those from hagfish caught in the open sea had a much lower PCB concentration (about 0.2 mg/kg of wet weight). No PCBs and no chlorinated pesticides were found in analyses of the mud at the catching site. High PCB concentrations (3 mg/kg of wet weight) were, however, observed in livers from cod living in the Gullmar Fjord, and it was proposed that bony fish may be the source of hagfish liver PCBs. PCB chromatograms of hagfish livers differed from those of PCB standards and cod liver. This strange pattern, which was not seen in livers from hagfish caught in the open sea, might be explained by an unusual mode of metabolization. The assays for aflatoxins gave completely negative results.

Adenoma, Bile Duct↗

[Immunofluorescent demonstration of pancreatic polypeptide (PP) in pancreas and digestive tube of bony and cartilaginous fish].

When antisera specific against bovine PP (BPP) were used, immunoreactive parenchymal cells were observed in the endocrine pancreas and in the gastro-intestinal tract of the teleost bony fish Cottus scorpius, as well as in the pancreas of the elasmobranchian cartilaginous fish Squalus acanthias. Of the two principal islets of Cottus, PP-cells were located selectively to that in the pyloric region.

Animals↗

Phylogeny of insulin. Some evolutionary aspects of insulin production with particular regard to the biosynthesis of insulin in Myxine glutinosa.

Preceding phylogenetic studies on the occurrence of insulin have shown--e.g. by bioassays and immunocytochemical procedures--that insulin producing B-cells are present in all vertebrates and even in several invertebrates, both protostomian and deuterostomian. The most original B-cells are obviously endocrine cells of open type, situated in the mucosa of the alimentary tract. Moreover, the results of these studies show that insulin is not only a polypeptide hormone of considerable age but also that the insulin molecule seems to have been kept surprisingly stable during evolution. Best known of all non-mammalian insulins is that from the hagfish, Myxine glutinosa. It is probably the most original insulin of all in the vertebrate series. Both the amino-acid sequence and the three-dimensional structure of the dimer of hagfish insulin differ only little from those of pig insulin. The biosynthesis occurs via proinsulin and is also in most respects similar to mammalian insulin biosynthesis. There are, however, some differences. Although it readily crystallizes as tetragonal bipyramids, hagfish insulin does not form hexamers. In a test system, with isolated rat fat cells, its binding affinity is 23% and its potency 5% of that of pig insulin, a discrepancy indicating a "partial antagonism" on the receptors. Although the conversion of proinsulin to insulin seems to occur in the secretion granules, they contain no crystalline cores. Since a strictly tryptic-like enzyme was found to destroy hagfish insulin rapidly, the enzyme converting proinsulin to insulin must--in addition to a carboxy-peptidase-B-like activity--have a different specificity in Myxine.

Amino Acid Sequence↗

Structural analysis of the molecular evolution of some gastro-entero-pancreatic hormones.

By means of a statistical analysis of the occurrence of amino-acid residues in the polypeptide chains of several gastro-entero-pancreatic (GEP) hormones an investigation was undertaken to determine whether any of these hormones might be related to each other--possibly from an evolutionary point of view. Particular interest was paid to the occurrence of small charged segments, i.e. those with acidic or basic amino acid residues, since such segments can be presumed to play a role in hormonal receptor binding mechanisms. By this method hormonal relationships were suggested by the observation that these small charged amino-acid sequences, contained in the hormonal structures, match as a result of non-randomness. It was found that hagfish and human insulin were related on a molecular level not only to the newly discovered (avian, bovine, human) pancreatic polypeptide (PP) but also to some other GEP hormones (VIP, GIP, glucagon) as well as to calcitonin and to the alpha-subunit of the glycoprotein hormones. Interpretation of the statistical data suggests that all these peptide hormones are related by a common hexapeptide sequence which contributed, at an evolutionary point, to their molecular architecture. A hexapeptide segment of APP is statistically related to a sequence of equal size in the carboxy terminal region of the A-chain of both hagfish and human insulin, providing the first instance of their structural similarity. Correlations between PP, insulin, glucagon, VIP, and calcitonin provide a tentative basis for predicting the production of one or more of these peptide hormones by immature or de-differentiated cells of neoplasms and non-neoplastic pathologic lesions of the GEP endocrine system.

Amino Acid Sequence↗