Biomedical subjects

S R Bloom

Publications and source records attributed to S R Bloom.

At least 703 records · Page 39Linked to original sources

PubMed1985

Vasoactive intestinal peptide: expression of the prohormone in bacterial cells.

A complementary DNA (cDNA) to the messenger RNA for the preprohormone of human vasoactive intestinal peptide (VIP) has been isolated and characterized. This cDNA extends from 65 bases 5' of the AUG translation start codon through the entire 3' untranslated region. Using this cDNA we have constructed expression plasmids which allow the synthesis of 120 out of the 150 amino acids of the prohormone in E. coli. This portion of the prohormone gene was either fused to a segment of a bacteriophage structural gene or expressed alone. When expression was induced the fusion protein constituted 15% of the total bacterial cell protein while the prohormone alone was 5%. Both proteins are recognized by antiserum raised against porcine VIP. They provide protein to study the precursor-product relationship of the hormone plus the possibility of identifying cryptic regulatory peptides contained within the prohormone.

Base Sequence↗

PubMed1985

Presence of neuromedin B-like immunoreactivity in the brain and gut of rat and guinea-pig.

A recently developed specific radioimmunoassay for neuromedin B, originally isolated from porcine spinal cord, was used to investigate its distribution in rat and guinea-pig brain and gut. In both species, neuromedin B-like immunoreactivity was present in several regions of brain, and high concentrations occurred in the pituitary. The immunoreactivity was widely distributed throughout the entire length of gastrointestinal tract and pancreas, and relatively high concentrations were found in the oesophagus and rectum. Immunocytochemistry localised neuromedin B-like immunoreactivity to nerve fibers in the rat brain and gut. Immunoreactive fibres were visualized in the medial thalamus and were found very frequently in the circular muscle of the gut. Gel permeation chromatography of pituitary and intestinal extracts from both species revealed presence of two peaks of neuromedin B-like immunoreactivity, the later of which co-eluted with the synthetic porcine neuromedin B standard. Reverse phase high pressure liquid chromatography showed that material corresponding to the later peak was eluted in the exact position of synthetic porcine neuromedin B, whereas the larger molecular size material from the earlier peak was more hydrophobic in nature.

Amino Acid Sequence↗

PubMed1985

Neuropeptides and 5-HT immunoreactivity in the gastric nerves of the dogfish (Scyliorhinus stellaris).

The gastric autonomic innervation of the dogfish was examined for regulatory peptides and serotonin by immunochemical techniques. Bouin's-fixed, paraffin-embedded or benzoquinone-fixed frozen sections were used for light microscopical immunocytochemistry and glutaraldehyde-fixed resin-embedded sections for electron microscopical immunocytochemistry. Bombesin-, somatostatin-, gastrin/cholecystokinin-, substance P-, peptide histidine isoleucine-, vasoactive intestinal peptide- and serotonin-immunoreactive nerves were found in all layers of the stomach wall. Bombesin and vasoactive intestinal peptide-containing nerves were identified at ultrastructural level. Radioimmunoassay of acetic acid extracts of tissue confirmed the presence of immunoreactivity for bombesin, somatostatin, substance P, peptide histidine isoleucine and vasoactive intestinal peptide. Reverse phase high performance liquid chromatography indicated that the peptides identified were broadly similar to their mammalian counterparts.

Animals↗

PubMed1985

Distribution of galanin immunoreactivity in the central nervous system and the responses of galanin-containing neuronal pathways to injury.

Radioimmunoassay and immunocytochemistry were used to study the distribution of galanin, a novel 29 amino acid porcine intestinal peptide, in the central nervous system of the rat and pig. The pattern of distribution was similar in the two species, with the highest concentrations of galanin-like immunoreactivity found in the neurohypophysis, hypothalamus and sacral spinal cord. Immunocytochemical studies of these regions localized galanin-like immunoreactivity to cell bodies in the paraventricular and supraoptic nuclei of the hypothalamus, to fibres in the pars nervosa and to numerous cell bodies and fibres in the dorsal horn of the spinal cord. On both gel and high pressure liquid chromatography, galanin-like immunoreactivity in rat and pig nervous tissue eluted as a single peak in a position similar to purified procine intestinal galanin standard. Surgical and pharmacological manipulations in the rat suggest the presence of galanin in afferent fibres. An increase of galanin-like immunoreactivity was observed in the sacral spinal cord of the rat following thoracic spinal cord transection. Thus galanin-like immunoreactivity in the brain is mainly localized in the hypothalamopituitary region. The decrease of galanin-like immunoreactivity in the dorsal horn of the spinal cord, following dorsal rhizotomy and pre-treatment of rats with capsaicin, indicates that many of the fibres, which are of small diameter, may well be derived from spinal sensory neurones.

Animals↗

PubMed1985

Immunohistochemical analysis of the early ontogeny of the neuropeptide Y system in rat brain.

The distribution of neuropeptide Y in the developing rat brain was studied with immunocytochemistry, using the peroxidase-antiperoxidase method. Immunoreactive perikarya were first seen on embryonic day 13 and staining of fibres appeared from embryonic day 15 onwards: perikaryal staining was generally more intense prenatally than after birth. Areas rich in neuropeptide Y immunostaining included the monoaminergic regions of the brain stem from embryonic day 13 (especially the lateral reticular nucleus and the medullary reticular formation), the dorsal mesencephalon (with spots of immunoreactivity in the outer subventricular zone at embryonic days 13 or 14 and many cells and fibres in the inferior colliculus from embryonic days 16-20) and the olfactory tubercle/ventral striatum from embryonic day 15 until birth. The period of development of cortical neurones extended from embryonic day 19 until postnatal day 21. A hitherto unreported feature unique to neuropeptide Y was the presence in certain parts of the cerebral cortex of transient cells at the base of the cortical plate bearing radial processes which transverse its width. They were present from embryonic day 17 until postnatal day 4 and were maximally developed at embryonic days 20 or 21, contributing at this age a substantial fibre projection through the immature corpus callosum. The abundance of neuropeptide Y in the prenatal rat brain suggests it may play an important role in development.

Age Factors↗

PubMed1985

Calcitonin gene-related peptide in cardiovascular tissues of the rat.

The distribution of calcitonin gene-related peptide immunoreactivity in the cardiovascular system of the rat was investigated by radioimmunoassay and immunocytochemistry. The nature of the immunoreactivity was studied by gel permeation and high performance liquid chromatography. Immunocytochemistry demonstrated the existence of calcitonin gene-related peptide-containing nerve fibres throughout the cardiovascular system. These were present in all regions of the heart, particularly in association with the coronary arteries, within the papillary muscles and within the sinoatrial and atrioventricular nodes. Calcitonin gene-related peptide-containing fibres were found mainly in the adventitia of the arteries and veins. Calcitonin gene-related peptide concentrations were high in major arteries and veins but comparatively low in the heart, aortic arch and thoracic aorta. Chromatography showed that approximately 70% of the total immunoreactivity was identical to synthetic calcitonin gene-related peptide. Calcitonin gene-related peptide concentrations in the blood vessels of rats treated neonatally with capsaicin were not found to be significantly different from those in control animals although capsaicin caused significant reductions of calcitonin gene-related peptide levels in certain other tissues. The results of this study suggest that calcitonin gene-related peptide-containing fibres are likely to be of importance in the innervation of vascular tissues and raise the possibility that these fibres are different in character from calcitonin gene-related peptide-containing fibres found in other tissues.

Animals↗

PubMed1985

Distribution and localization of neuromedin B-like immunoreactivity in pig, cat and rat spinal cord.

The distribution and localization of neuromedin B, a novel bombesin-like decapeptide isolated from porcine spinal cord, was investigated by newly established radioimmunoassay and immunocytochemistry in the pig, cat and rat spinal cord. Neuromedin B-like immunoreactivity was found to be concentrated particularly in the dorsal part of lumbosacral segments in all species studied and the highest concentration of immunoreactivity was 25.7 +/- 3.4 pmol/g wet wt in the dorsal part of sacral region of pig spinal cord. The nature of the immunoreactivity was studied by gel permeation and high pressure liquid chromatography. Chromatography of spinal cord extracts from three species revealed two major peaks of neuromedin B-like immunoreactivity and the prevalent molecular from co-eluted with synthetic porcine neuromedin B. Immunocytochemistry localized neuromedin B immunoreactivity to fibres and terminals throughout the entire length of the spinal cord of pig, cat and rat. Fibres were most abundant in laminae I and II of the dorsal horn, the area around the central canal (lamina X) and intermediolateral cell columns of thoracic and sacral segments. In lumbosacral segments neuromedin B-immunoreactive fibres were slightly more numerous, in both dorsal and ventral spinal cord, than in cervical and thoracic regions.

Animals↗

PubMed1985

Long-term treatment of a VIPoma with somatostatin analogue resulting in remission of symptoms and possible shrinkage of metastases.

A 43-yr-old-man with metastatic VIPoma in whom the conventional measures of surgery, chemotheraphy, and hepatic artery embolization ultimately failed to control his severe diarrhea, resulting from vasoactive intestinal polypeptide hypersecretion, was treated with a new long-acting somatostatin analogue, SMS 201-995, for 14 mo. SMS 201-995 not only controlled the diarrhea without side effects but appeared to have possibly induced a reduction in metastatic tumor size.

Adenoma, Islet Cell↗

PubMed1985

Can the human neonate mount an endocrine and metabolic response to surgery?

Little is known of the ability of the human newborn infant to mount an endocrine and metabolic response to surgical trauma. Blood concentrations of glucose, lactate, pyruvate, alanine, hydroxybutyrate, acetoacetate, and glycerol together with plasma concentrations of insulin, glucagon, adrenaline, and nonadrenaline were measured in 33 infants (26 term, 7 preterm) subjected to surgery during the neonatal period. The results show that newborn infants can indeed mount a substantial endocrine and metabolic stress response, the main features of which are hyperglycemia and hyperlactatemia associated with the release of catecholamines and the inhibition of insulin secretion. There are specific differences between preterm and term neonates and between neonates anesthetised by different anesthetic techniques in the pattern of this response.

Anesthetics↗

PubMed1985

Changes in vascular resistance in the feline urinary bladder in response to bladder filling.

The effect of bladder filling on vesical blood flow was studied in anesthetized cats. The pelvic nerves were sectioned and the bladder venous outflow was recorded by a drop counter. Filling of the bladder induced a sustained increase in vesical blood flow, related to the bladder volume. Thus, injection of 10, 20 and 30 ml. of saline decreased bladder vascular resistance by 27, 47 and 52 per cent, respectively. This vasodilation occurred despite a steady state increase in bladder pressure by 25 to 50 cm. H2O. Upon emptying of the bladder, blood flow decreased towards control values. The response was unaffected by alpha-adrenoceptor blockade (phentolamine), beta-adrenoceptor blockade (propranolol) and muscarinic cholinoceptor blockade (atropine). The vasodilation was eliminated by papaverine, indicating that the response was not due to a rearrangement of the vessels at large bladder volumes. The vasodilation was not associated with any increase in the concentrations of vasoactive intestinal polypeptide (VIP) or substance P in the venous effluent blood. Indomethacin significantly reduced the vasodilatation induced by filling. We conclude that local mechanisms, possibly involving release of prostaglandins, are involved in the vasodilation following bladder distension.

Animals↗

PubMed1985

Neuropeptides in the brain.

In recent years, there has been a remarkable increase in the identification of neuropeptides. These peptides have become known as neuropeptides, as they have been identified within neuronal structures and frequently localised to nerve terminals. Classification of newly discovered peptides is attempted according to function or structure. Although the role of the hypothalamic releasing factors is readily appreciated, the functional significance of the remaining neuropeptides is often not easily determined. However, these peptide appear to interact with conventional transmitters and may be implicated in neuropathology.

Alzheimer Disease↗

PubMed1985

Neuropeptide Y: a novel renal peptide with vasoconstrictor and natriuretic activity.

A novel vasoconstrictor peptide, neuropeptide Y (NPY), has been identified in considerable quantities in the renal artery and kidney. Within the kidney, NPY was confined to the cortex and corticomedullary interface, the regions where the juxtaglomerular apparatus is most numerous. In the isolated perfused rat kidney, NPY caused a prompt dose-dependent increase in perfusion pressure and reduction in flow, with only a small fall in glomerular filtration rate (GFR). In spite of the reduced renal perfusion, a dose-dependent natriuresis was observed. This response contrasts to the response of this preparation to noradrenaline, which causes sodium reabsorption. The presence of a potent vasoconstrictor and natriuretic peptide within the rat renovascular system suggests that it may play a significant role in the control of renal function.

Animals↗

PubMed1985

Day profiles of glucose dependent insulinotropic polypeptide (GIP) in normal subjects.

IRGIP release results from nutrient absorption, the major stimulants being fat and carbohydrate. Little is known, however, about its diurnal profile in response to serial meals. The purpose of this study was to determine the plasma IRGIP day profile in normal subjects following four isocaloric meals administered serially throughout the day. Five healthy normal weight (67-77 kg) male volunteers aged 38-49 years were investigated following a 10 hour overnight fast on two days. On each day, isocaloric non-identical test meals were consumed at 09.00, 13.00, 16.00 and 19.00 hours. Plasma glucose, insulin (IRI), IRC-peptide and IRGIP levels were measured half-hourly from 08.30 to 21.00 hours. Peak IRGIP levels occurred within 2 hours of the commencement of each meal and then decreased gradually but never returned to fasting levels. Compared with the first meal, the subsequent pre-prandial IRGIP levels were significantly higher (P less than 0.05) which was consistent for the two study days. The highest mean IRGIP levels occurred after breakfast and tea which were the meals containing the greater proportion of fat. Plasma IRGIP levels correlated (P less than 0.001) with the concentrations of both insulin and IRC-peptide. In conclusion, plasma IRGIP levels increased following ingestion of serial mixed meals but the levels did not return to fasting concentration throughout the day. There was a gradual upward trend of each subsequent pre-prandial IRGIP value. The physiological importance of this observation requires further exploration.

Adult↗

PubMed1985

Calcitonin gene-related polypeptide as a mediator of the neurogenic ocular injury response.

Calcitonin gene-related polypeptide (CGRP) has been localised immunochemically within the rat and guinea pig anterior uvea to nerve fibres of trigeminal origin. As with substance P (1-3) the level of CGRP in the iris-ciliary body is depleted after thermal damage to the Gasserian ganglion and elevated in chronically sympathectically denervated eyes. Unlike substance P, a potent pupillary constrictor (4,5), CGRP has no notable miotic action, but does, however, cause an elevation of the intraocular pressure (IOP) accompanied by disruption of the blood-aqueous barrier. It is proposed that the diverse actions of these two sensory neuropeptides conjointly mediate the antidromic ocular injury response.

Afferent Pathways↗

PubMed1985

Gastrin-releasing peptide-like immunoreactivity in medullary thyroid carcinoma.

Gastrin-releasing peptide, the mammalian counterpart of amphibian bombesin, has been found to be present in high concentration by radioimmunoassay in eight histologically confirmed medullary thyroid carcinomas and to be undetectable in postmortem normal thyroid tissue. Chromatographic analysis of the tumor extracts by gel permeation revealed two major peaks of gastrin-releasing peptide-like immunoreactivity (GRP-LI). However, reverse-phase high-pressure liquid chromatography demonstrated three immunoreactive peaks of GRP-LI. None of these immunoreactive peaks was coeluted with synthetic porcine GRP or amphibian bombesin, but one of the peaks exactly emerged in the position of neuromedin C (C-terminal decapeptide of GRP). Sections from nine primary or secondary tumours were immunostained for GRP using a peroxidase/anti-peroxidase technic. All the medullary thyroid carcinomas were shown to contain GRP-LI, specifically localized to the tumor cells. This immunoreactivity is elevated in plasma from some patients with this malignancy, raising the possibility that it may be used as an additional tumor marker.

Carcinoma↗

PubMed1985

Localisation of neuropeptide Y in nerves of the rat cardiovascular system and the effect of 6-hydroxydopamine.

The distribution of neuropeptide Y (NPY) in the rat cardiovascular system has been examined by radioimmunoassay, chromatographic analysis of tissue extracts, and immunocytochemistry. High concentrations of NPY were identified throughout the heart and within the major blood vessels of the rat in particular in the renal and superior mesenteric arteries. NPY-immunoreactivity was localised to dense plexuses of nerves in the adventitia of the arteries. Treatment of rats with 6-hydroxydopamine resulted in a significant reduction of NPY concentrations in the major vessels. A depletion of extractable NPY was also seen in the heart of the treated animals. Only few degenerated NPY-containing nerve fibres (swollen and fragmented) were observed in the heart and in the adventitia of the blood vessels. It is concluded that NPY containing nerves of the heart and blood vessels are sensitive to treatment with 6-hydroxydopamine. The pharmacological properties of this peptide suggest that these NPY-containing nerve fibres may act as efferent vasoconstrictor nerves to the blood vessels.

Adrenergic Fibers↗

PubMed1985

Selective alpha 2 receptor blockade facilitates the insulin response to adrenaline but not to glucose in man.

The adrenergic nervous system plays an important role in the control of insulin release and animal work suggests that this is mediated by way of alpha 2 adrenoceptors. A specific alpha 2 adrenoceptor antagonist (idazoxan) is now available for use in man and we have studied its effects on insulin release in normal volunteers (a) during the infusion of adrenaline (0.05 micrograms/kg/min) and (b) after an intravenous dose of glucose (20 g). The infusion of adrenaline alone had no significant effect on insulin release while in the presence of idazoxan, insulin release was markedly stimulated by adrenaline. Despite this, adrenaline-induced hyperglycaemia was unaffected by pretreatment with idazoxan. In the second study, pretreatment with either idazoxan or a specific alpha 1 antagonist (prazosin) had no significant effect on either glucose tolerance, glucose-induced insulin release or glucose-induced suppression of glucagon. Intravenous glucose also had no significant effect on pancreatic polypeptide levels. Therefore the effect of adrenaline on insulin release is mediated by way of inhibitory alpha 2 adrenoceptors in the pancreas, while the release of insulin in response to glucose in a resting subject is independent of the alpha-adrenergic system.

Adult↗

PubMed1985

Effect of calcitonin on gastrointestinal regulatory peptides in man.

A major physiological role of calcitonin in humans appears to be regulation of skeletal turnover. It has been suggested that another function of calcitonin is to prevent post-prandial rises in calcium, particularly in animals, but the importance of such a function in man remains to be determined. Although it is known that calcitonin has an inhibitory effect on the secretion of gastrin and insulin, its actions on other gut and pancreatic hormones have not previously been studied. To investigate interrelations between calcitonin and gastrointestinal regulatory peptides, 0.5 mg synthetic human calcitonin was administered to 10 fasting patients. No changes in the plasma concentrations of glucose, somatostatin, neurotensin, enteroglucagon, vasoactive intestinal polypeptide or bombesin were observed. In contrast, profound falls in the circulating levels of gastrin, insulin and pancreatic glucagon were seen, reaching a maximum shortly after the peak of plasma calcitonin concentration. Marked changes were also observed in the levels of motilin, pancreatic polypeptide and, to a lesser extent, gastric inhibitory polypeptide, but the maximal falls occurred about 40 min later, coinciding with a significant fall in serum calcium. It is possible that the effect of calcitonin on these hormones was direct, perhaps receptor-mediated. The falls in levels of motilin and pancreatic polypeptide could have been further enhanced by changes in extracellular calcium ion concentrations. Whether any of these effects of calcitonin occur physiologically remains to be determined. However, these findings suggest new therapeutic possibilities for calcitonin.

Adult↗