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Biomedical subjects

S Falkmer

Publications and source records attributed to S Falkmer.

At least 73 records · Page 4Linked to original sources
PubMed1987

Primary structures of three fragments of proglucagon from the pancreatic islets of the daddy Sculpin (Cottus scorpius).

Three peptides isolated from the Brockmann bodies of the daddy sculpin, a teleostean fish, have been identified as fragments of one or more proglucagons. The peptide L Q D A E D S S R F D A D D T L A G E A R E L S T P K represents the NH2 terminus of proglucagon (residues 1-27), H S E G T F S N D Y S K Y L E T R R A Q D F V Q W L K N S represents glucagon and H A D G T F T S D V S S Y L N D Q A I K D F V A K L K S G K V represents the glucagon-like peptide at the COOH terminus of the precursor. The fast-atom bombardment mass spectra of the three peptides were consistent with the proposed structures and demonstrated that further posttranslational modifications of the peptides had not taken place. Sculpin glucagon is identical to anglerfish glucagon II but sculpin proglucagon(1-27) and glucagon-like peptide show stronger homology to the corresponding regions of anglerfish proglucagon I than to proglucagon II. The structures of the peptides are suggestive of the action of trypsin-like and carboxypeptidase-B-like enzymes at the site of pairs of basic amino acid residues in proglucagon. The presence of a COOH-terminal lysyl group in proglucagon(1-27) may indicate, however, that the penultimate prolyl residue partially inhibits the action of the carboxypeptidase-B-like activity.

Amino Acid Sequence↗
PubMed1987

Electronmicroscopical, immunohistochemical, immunocytochemical and biological evidence for the occurrence of cardiac hormones (ANP/CDD) in chondrichthyes.

As representatives of the vertebrate class of chondrichthyes the plagostomian species Squalus acanthias, Scyliorhinus canicula and Raja clavata as well as the holocephalan species Chimaera monstrosa were investigated for the presence of cardiac hormones of the atrial natriuretic polypeptide/cardiodilatin- (ANP/CDD-) family. ANP/CDD-immunoreactive cells were detected in the atria and the ventricles of all species studied. While these cells failed to react with antisera raised against the N-terminus of CDD-126 (= gamma-ANP) they reacted with all antisera directed against sequences of the C-terminus of CDD-126 (CDD 99-126) which is identical to alpha-ANP. The ANP/CDD-immunoreactive cells were found in high numbers in all regions of the atria and in moderate density also in the ventricles. In correspondence, in the electron microscope, myoendocrine cells which were characterized by dense-cored secretory granules were identified in the atrial and ventricular myocardium. With the use of the protein A-gold technique, ANP/CDD-immunoreactivity was determined within the secretory granules. Furthermore, in the bioassay, prepurified extracts of the atria and the ventricles of Scyliorhinus and Chimaera exerted dose-dependent relaxations of the pre-contracted mammalian (rabbit) aorta. In both cases the atrial extracts proved to be more potent than the ventricular extracts. The present findings indicate that myoendocrine cells occur in the atria and ventricles of chondrichthyes and that these cells contain homologous cardiac hormones of the ANP/CDD-family in their secretory granules. The results are compared with those obtained earlier for the other vertebrate classes and their phylogenetic and functional significance is discussed.

Animals↗
PubMed1987

Polypeptide YY- and neuropeptide Y-immunoreactive cells and nerves in the endocrine and exocrine pancreas of some vertebrates: an onto- and phylogenetic study.

The occurrence of polypeptide YY- and neuropeptide Y-immunoreactive cells and nerves in the pancreas of some species from all the eight main vertebrate groups (cyclostomes, cartilaginous fish, bony fish, amphibia, reptiles, birds, and mammals) was investigated. In addition, an ontogenetic study of these neurohormonal peptides was performed, using the rat pancreas. The distribution of these two peptides was compared with that of the structurally closely related pancreatic polypeptide. Polypeptide YY-immunoreactive cells were found to occur in the endocrine pancreas and neuropeptide Y-immunoreactivity was observed both in neurons and nerve fibres. The polypeptide YY-immunoreactive cells were limited to mammals and reptiles only. Neuropeptide Y-immunoreactive neurons and nerves were observed in reptiles, birds, and mammals only. One reptilian species (out of three) and one mammalian (out of six) failed to show any kind of immunoreactivity for the polypeptide or neuropeptide. Pancreatic polypeptide-immunoreactive cells were found in all the species examined except in the hagfish islet. In rat foetuses, polypeptide YY-immunoreactive cells and neuropeptide Y-immunoreactive nerve elements were first demonstrated at the seventeenth day of gestation, whereas pancreatic peptide-immunoreactive cells did not appear until postnatally, namely in two day-old rats. The polypeptide-containing cells, a new cell type in the endocrine pancreas, are rare. In contrast to the pancreatic peptide cells, they do not seem to have any kind of regional distribution.

Animals↗
PubMed1987

Peptide-hormone- and serotonin-immunoreactive tumour cells in carcinoma of the prostate.

In order to establish the extent of neuroendocrine differentiation and the occurrence of neurohormonal peptides in the neoplastic cells of prostatic carcinomas, silver-staining and immunocytochemical techniques were used. All gave satisfactory results. The incidence of the neuroendocrine cells seemed to be higher in the fresh "Bouin-fixed" biopsy specimens than in the conventionally "formalin-fixed" specimens from archival paraffin blocks. All carcinomas demonstrated argyrophil cells as an integral element of the tumour. In highly differentiated carcinomas (grade I) these cells were scattered focally, intermingled with non-argyrophil cells in typical adenocarcinomas; their incidence was estimated to be about the same as in benign prostatic hyperplasia. Most of them were immunoreactive with antisera raised against serotonin and/or TSH (thyroid stimulating hormone). In moderately and poorly differentiated (grades II-III) carcinomas, however, the argyrophil cells were more numerous and showed greater variation in growth pattern; only occasionally they displayed a typical carcinoid-like structure. Moderately and poorly differentiated carcinomas also showed a greater variation in the number and kinds of peptide immunoreactivities than the highly differentiated carcinomas. In addition to serotonin- and TSH-immunoreactive cells as the most prevalent type, now also human chorionic gonadotrophin (HCG-alpha), adrenocorticotropic hormone (ACTH), leu-enkephalin, beta-endorphin, somatostatin, glucagon and calcitonin immunoreactive cells could be found within certain tumour areas and often with a distinctly patchy distribution. In two cases, where the tumour cells in the metastases were also investigated, they were found to be both argyrophil and immunoreactive with the same antisera as those of the primary tumour. Our findings emphasise the fact that prostatic carcinomas are more complex and heterogenous than previously thought, exhibiting endocrine differentiation as an integral element of virtually all prostatic adenocarcinomas.

Adenocarcinoma↗
PubMed1987

Neuroendocrine background of the pathology of the islets of Langerhans. A minireview with particular reference to synaptophysin and chromogranin A as neuroendocrine markers and to the ontogeny of argyrophil insulin immunoreactive cells in the rabbit.

As in diseases of other (neuro)endocrine glands, the pathology of the islets of Langerhans comprises both states of hypofunction, notably hypoinsulinism,--diabetes mellitus--and those of hyperfunction, such as hyperinsulinism from either nesidiodysplasia ("nesidioblastosis") or genuine islet-cell neoplasms. The pathogenesis of some characteristic structural lesions of these diseases of the islet parenchymal cells is reviewed against their neuroendocrine background, both phylogenetically and ontogenetically. A preliminary report is given of the appearance of argyrophil insulin cells during the normal foetal development of the islet parenchyma of the rabbit. In addition, the distribution of the newly discovered neuroendocrine markers synaptophysin and chromogranin A has been reviewed immunohistochemically in normal and neoplastic islet parenchyma cells; the insulin cells do not seem to contain chromogranin A.

Animals↗
PubMed1987

Biochemical, immunohistochemical and ultrastructural studies of the alteration of pancreatic beta cells resulting from the combined effects of complete Freund's adjuvant and non-diabetogenic doses of streptozotocin.

Injection of complete Freund's adjuvant (CFA) 24 h prior to treatment of rats with non-diabetogenic doses of streptozotocin (STZ) produced a reduction in pancreatic insulin content associated with ultrastructural changes and a decrease of the volume density of insulin-immunoreactive cells without affecting other islet cells. After one injection of CFA and STZ, pancreatic insulin content was decreased by 69% (p less than 0.01) within 48-96 h, while plasma glucose concentrations were not changed. The volume density of beta cells in pancreata of these rats was reduced by 40% (p less than 0.01) compared with citrate-saline treated control rats. No significant lymphocytic infiltration was detectable in islets, but the exocrine pancreas exhibited inflammatory lesions. Degranulation and vacuolation was evident by ultrastructural analysis. Following administration of CFA or STZ alone, pancreatic insulin content was insignificantly reduced, and major histopathological changes in pancreatic islets were apparently absent. These results support the hypothesis that activation of the immune system by CFA allows an anti-beta cell reaction to develop following exposure to the beta cell toxic agent STZ.

Animals↗
PubMed1987

Ontogeny of the pancreatic islet parenchymal cells in the rabbit--an immunohistochemical and ultrastructural study with particular regard to the earliest appearance of argyrophil insulin-immunoreactive cells.

Six early developmental stages of the rabbit pancreas were selected, viz. the embryonic ages 10 days 10 hours, 10 days 18 hours, 11 days 14 hours, 13 days, 15 days, and 18 days. Both non-immunological (histologic-tinctorial features, including argyrophilia, and transmission electron microscopy) and immunohistochemical (the indirect immunofluorescence and/or the peroxidase-anti-peroxidase procedure) methods were used to follow the time-course for the appearance and differentiation of both endocrine (islet) cells and exocrine acinar epithelium. The immunological procedures were, however, limited to the 3 later developmental stages. In the first 3 developmental stages only the dorsal anlage of the pancreas could be found. It was just investigated ultrastructurally. Then, a few parenchymal cells were observed, equipped with secretory granules of endocrine type, indicating that an early differentiation of islet cells had already begun. In the later 3 developmental stages a ventral pancreas anlage was present and at least 2 types of argyrophil islet cells, equipped with secretory granules, were observed. In the pancreas anlage of 13-day-old embryos these early endocrine cells were found to be glucagon-immunoreactive. At the developmental age of 15 days argyrophil insulin-immunoreactive cells were also present, and in the 18-day-old embryos a few somatostatin cells could occasionally be discovered, too. No PP cells were found. Any exocrine acinar differentiation (with zymogen granules) was not observed until at the developmental age of 18 days.

Aging↗
PubMed1987

Tissue cultivation as a method for preservation of human foetal islet parenchyma--a correlated biochemical, immunohistochemical and morphometric investigation.

Tissue culture of human foetal pancreas slices, obtained at a gestational age between 10 and 19 weeks, as a method of preservation and to pool the material before transplantation was investigated. Before and after 2 weeks of culture the pancreatic insulin content, the insulin secretion in response to glucose and isobutylmethylxanthin (IBMX) as well as the protein biosynthesis were measured. In addition, the distribution of the insulin immunoreactive cells was examined, as well as their relative volume density. After 2 weeks' culture an increase of the basal insulin secretion was observed; this was probably due to the glucose content (10 mmol/l) in the culture medium. Neither the stimulated insulin secretion, nor the protein biosynthesis, the insulin content, and the B-cell volume were altered by the used culture conditions. It was concluded that tissue culture is a suitable method to preserve human foetal pancreas slices before transplantation.

Culture Techniques↗
PubMed1987

Destruction of pancreatic beta cells in rats by complete Freund's adjuvant combined with non-diabetogenic doses of streptozotocin.

Non-specific activation of the immune system by complete Freund's adjuvant (CFA) in combination with non-diabetogenic doses of streptozotocin (STZ) was used to study autoimmune reactions against pancreatic islets. Male Lewis RT1a rats received either CFA (0.5 ml/kg) 24 hr prior to the injection of STZ (25 mg/kg), or CFA or STZ alone. The injections of CFA followed by STZ, but not CFA or STZ alone, produced a 69% (p less than 0.01) reduction in pancreatic insulin content associated with necrosis and a decrease of the relative volume density of insulin-immunoreactive cells without affecting other islet cells. Two injections of CFA and STZ induced hyperglycemia. This was associated with a depletion of pancreatic insulin and a significant reduction in the relative volume density of insulin-immunoreactive cells (p less than 0.01) and in the mean islet area (p less than 0.01). On day 20, after treatment with 3 injections of CFA and STZ, the animals developed persistent hyperglycemia. The pancreata in these rats contained less than 12% B-cells, and the insulin content was reduced by 96% (p less than 0.01). The main components of the remaining atrophic islets were glucagon- and somatostatin-immunoreactive cells. No significant lymphocytic infiltration into the islets was detectable, but the exocrine parenchyma exhibited severe inflammatory lesions. Degranulation and vacuolation of B-cells was evident by ultra-structural analysis. The volume densities of insulin containing cells and islet area were not changed after 3 injections of either CFA or STZ alone, although the pancreatic insulin content decreased by 61% (p less than 0.01) and 39% (p less than 0.05), respectively. These treatments did not produce an increase in plasma glucose. The present results demonstrate that CFA in combination with non-diabetogenic doses of the beta cytotoxic agent STZ induces B-cell destruction without significant insulitis. Our observations support the hypothesis that activation of the immune system by CFA allows an anti-B-cell immune reaction to develop following exposure to STZ.

Animals↗
PubMed1987

Synaptophysin. A new marker for pancreatic neuroendocrine tumors.

Synaptophysin (SYP) is a glycoprotein recently isolated from presynaptic vesicles of bovine neurons. Initial studies have demonstrated its presence in neurons in the brain, spinal cord and retina, and in adrenal medullary cells. A subsequent study demonstrated it in pancreatic islet cells and certain neuroendocrine (NE) neoplasms, including several pancreatic islet cell tumors. Based on these preliminary observations, we examined, by immunohistochemistry, conventionally fixed, paraffin sections of 57 pancreatic endocrine tumors with a monoclonal antibody to SYP. Furthermore, we compared the SYP immunoreactivity of 30 of these same tumors with that of neuron-specific enolase (NSE) and of chromogranin (CG). SYP was demonstrated in all but one of the 57 tumors. In the comparative study, for which material was available in only 30 cases, SYP and NSE were present in 29 of the tumors, whereas CG was seen in only 15 cases. We conclude that SYP is a highly sensitive and useful marker for pancreatic NE neoplasms. Moreover, in view of the increasingly evident limited specificity of NSE, SYP should be considered the marker of choice for pancreatic NE neoplasms.

Adenoma, Islet Cell↗
PubMed1986

Characterization of an amidated form of pancreatic polypeptide from the daddy sculpin (Cottus scorpius).

The primary structure of pancreatic polypeptide from the teleostean fish, Cottus scorpius (daddy sculpin) was established as: YPPQPESPGGNASPEDWAKYHAAVRHYVNLITRQRYNH2 The presence of a COOH-terminally alpha-amidated amino acid was established using an HPLC method of general applicability. Although the peptide shows strong homology towards anglerfish pancreatic polypeptide (86%), homology towards porcine peptide YY (PYY) (61%) and porcine neuropeptide Y (NPY) (61%) was greater than towards porcine pancreatic polypeptide (PP) (47%). This result supports suggestions that the gene duplication events which led to PP, NPY and PYY formation took place after the time of divergence of fish and mammals.

Amino Acid Sequence↗
PubMed1986

The primary structure of ratfish insulin reveals an unusual mode of proinsulin processing.

The primary structure of insulin from the Holocephalan fish, Hydrolagus colliei (the ratfish), has been established by automated Edman degradation as: (Formula: see text). The presence of a COOH-terminal extension to the B-chain is consistent with the occurrence of a single base mutation in the region of the gene encoding one of the dibasic residue processing sites [Arg31(AGA)----Ile* (AUA)] with the result that the ratfish has utilised an alternative cleavage site within the C-peptide region of proinsulin.

Amino Acid Sequence↗
PubMed1986

The isolation, purification and amino-acid sequence of insulin from the teleost fish Cottus scorpius (daddy sculpin).

Insulin from the principal islets of the teleost fish, Cottus scorpius (daddy sculpin), has been isolated and sequenced. Purification involved acid/alcohol extraction, gel filtration, and reverse-phase high-performance liquid chromatography to yield nearly 1 mg pure insulin/g wet weight islet tissue. Biological potency was estimated as 40% compared to porcine insulin. The sculpin insulin crystallised in the absence of zinc ions although zinc is known to be present in the islets in significant amounts. Two other hormones, glucagon and pancreatic polypeptide, were copurified with the insulin, and an N-terminal sequence for pancreatic polypeptide was determined. The primary structure of sculpin insulin shows a number of sequence changes unique so far amongst teleost fish. These changes occur at A14 (Arg), A15 (Val), and B2 (Asp). The B chain contains 29 amino acids and there is no N-terminal extension as seen with several other fish. Presumably as a result of the amino acid substitutions, sculpin insulin does not readily form crystals containing zinc-insulin hexamers, despite the presence of the coordinating B10 His.

Amino Acid Sequence↗
PubMed1986

Peptide-hormone- and serotonin-immunoreactive cells in normal and hyperplastic prostate glands.

Peptide-hormone- and serotonin-immunoreactive cells of endocrine type are present both in the normal prostatic gland and in the nodules of benign prostatic hyperplasia of man. They are located in the epithelium of the acini and the ducts of all the different parts of the gland, as well as in the urothelium of the prostatic part of the mucosa of the urethra. The endocrine cells are usually argyrophil, sometimes even argentaffin, and immunoreactive with neuron-specific enolase; they can be either of open or of closed type and usually occur widely scattered as single cells. Three kinds of endocrine cells were observed both in the normal gland and in the hyperplastic parenchyma. In the by far most prevalent type serotonin was found to co-exist with a peptide immunohistochemically related to the thyroid stimulating hormone (TSH). In a more rare type serotonin co-existed immunohistochemically with calcitonin. The third kind of endocrine cells was somatostatin-immunoreactive cells; they were also rather rare. The only difference observed between the normal and hyperplastic parenchyma was an increase in the number of all the three kinds of endocrine cells in the hyperplastic nodules. The endocrine cells could easily be visualized by means of silver-staining techniques, even using conventionally formalin-fixed, paraffin-embedded specimens.

Adult↗
PubMed1986

Patterns of DNA distribution and neurohormone immunoreactivity in the tumour cells: tools for the histopathological assessment of gastro-intestinal carcinoids.

Modern immunohistochemical and DNA cytochemical analyses of gastro-intestinal carcinoids have yielded results that have increased our knowledge of the biological properties and the histogenesis of these theoretically and practically so fascinating kinds of neoplasm. Carcinoids in different anatomical localisations were found to show marked differences with regard to their neurohormone peptide immunoreactivity pattern and their ability to evoke clinical signs and symptoms of hormone overproduction. This can be of great help to the practising pathologist when he tries to predict the anatomical site of an unknown primary tumour from the results of this histopathological assessment of a metastatic nodule of a carcinoid. The DNA distribution pattern in the nuclei of carcinoid tumour cells is a tool in the histopathological assessment of the neoplasm that seems to be of some value in predicting the subsequent clinical course of the disease. This conclusion is based on the results of a pilot study of 8 cases of ileal carcinoids with liver and lymph node metastases. It was found that 4 cases with a rapidly progressive fatal disease had a higher proportion on non-diploid tumour cell nuclei than 4 cases still alive and at full work 5 years after the diagnosis of liver metastases. However, the number of aneuploid tumour cell nuclei was negligible in both groups.

Adult↗