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Biomedical subjects

S R Bloom

Publications and source records attributed to S R Bloom.

At least 649 records · Page 36Linked to original sources
PubMed1986

Effect of haemodialysis on plasma concentrations of atrial natriuretic peptide in adult patients with chronic renal failure.

Twenty patients with chronic renal failure were studied before and after haemodialysis. Plasma atrial natriuretic peptide (ANP) concentrations were markedly elevated (P less than 0.01) before dialysis in comparison with healthy control subjects. After haemodialysis the plasma ANP concentration was lower in 19 patients (P less than 0.01) but remained above the normal range in all but three cases. Systolic and diastolic blood pressure and body weight fell during dialysis but none of these changes correlated with the reduction of the plasma ANP concentration. Chromatographic analysis of plasma extracts indicated that alpha-ANP is the predominant circulating molecular form. The increase in concentration of ANP in plasma between dialyses, at a time when many patients are susceptible to sodium and water overload, and its return towards normal after dialysis supports the putative role of ANP as a circulating factor released in response to sodium and water accumulation.

Adolescent↗
PubMed1986

Establishment of a continuous somatostatin-producing line of medullary thyroid carcinoma cells from BALB/c mice.

A continuous line of somatostatin-producing medullary thyroid carcinoma cells was established from a transplantable tumour in BALB/c mice. Virtually all of the somatostatin immunoreactivity co-chromatographed with somatostatin 14. The tumour cells replicated in spinner cultures with a doubling time of approximately 4 days, and the concentration of somatostatin released into the culture medium increased in proportion to the number of cells. Two- to threefold increases in amounts of stored and released somatostatin were observed after treatment of the cells with bromodeoxyuridine. This cell line might be valuable for studies of somatostatin regulation in normal and neoplastic C-cells, and for other studies of C-cell biology which require a mouse model.

Animals↗
PubMed1986

Reduction by morphine of human postprandial insulin release is secondary to inhibition of gastrointestinal motility.

The effect of morphine (0.1 mg/kg) on insulin secretion stimulated by oral, intraduodenal, or intravenous administration of glucose was studied in seven healthy volunteers. When glucose was given intravenously, morphine had no effect on plasma glucose, insulin, glucose-dependent insulinotropic polypeptide (GIP), or pancreatic glucagon. Following oral glucose, morphine slowed gastric emptying and reduced plasma concentrations of glucose, insulin, and GIP. During intraduodenal infusion of glucose, insulin concentrations in plasma were also decreased by morphine, an effect best explained by decreased small intestinal transit with delayed absorption of glucose and delayed release of GIP. We conclude that clinically relevant doses of morphine have no direct effect on insulin secretion and that the changes observed were secondary to slowed gastric emptying and small intestinal transit.

Adolescent↗
PubMed1986

Somatostatin localization in tissues.

The development of specific antibodies to somatostatin has enabled investigations on the distribution (radioimmunoassay) and precise tissue localization (immunocytochemistry) of somatostatin-immunoreactive (IR) material. Somatostatin immunoreactivity is broadly distributed both in the central nervous system and in many peripheral organs, including the gastrointestinal tract, pancreas, genitourinary system, heart, eye, thyroid, thymus, and skin. Somatostatin-IR cells display characteristic morphological features, including cytoplasmic elongations, which lend support to the postulated local or paracrine role for somatostatin. The intracytoplasmic electron-dense secretory granules in somatostatin-IR endocrine cells are characterized by their round shape, flocculent matrix, and closely apposed limiting membrane. Somatostatin-IR nerves are abundant in the gut and contain large, dense, P-type neurosecretory granules, which are distinct from those storing other peptidergic neurotransmitters. Somatostatin immunoreactivity is found frequently in neuroendocrine tumours, but the existence of the 'somatostatinoma syndrome' has recently been questioned.

Animals↗
PubMed1986

Postprandial effects of SMS 201-995 on gut hormones and glucose tolerance.

SMS 201-995 (5-100 micrograms) injected subcutaneously in normal and type-2 diabetic subjects 30 min before a test meal caused dose-related suppression of plasma concentrations of insulin, glucagon, and several regulatory gut peptide hormones (gastrin, gastric inhibitory peptide, pancreatic polypeptide, secretin, neurotensin, and motilin). Effective hormone suppression was achieved even at the lowest dose of 5 micrograms. In the normal subjects SMS caused postprandial hyperglycaemia, but there was no overall deterioration in glucose tolerance in the type-2 diabetic patients. This suggests that counterregulatory hormones play an important part in the metabolic disturbance of type-2 diabetes.

Aged↗
PubMed1986

Neuroendocrine tumours of the gut: long-term therapy with the somatostatin analogue SMS 201-995.

Nine patients with metastatic neuroendocrine tumours of the gut were treated for over 100 days with the long-acting octapeptide of somatostatin, SMS 201-995. Two patients had unusually aggressive tumours (neuroendocrine tumours are typically slow-growing) with only modest elevation of tumour secretory products. SMS 201-995 was given in an attempt to slow tumour growth, but tumour size continued to increase. Three patients had glucagonomas and uncontrolled skin rashes, and four patients had VIPomas, which caused uncontrolled watery diarrhoea. SMS 201-995 was given principally to reduce hypersecretion of hormones from their tumours and to relieve symptoms. All the patients experienced rapid relief of their symptoms when SMS 201-995 treatment was introduced, and symptomatic control was maintained throughout treatment except in one patient, who required a supplementary procedure (pancreatic primary tumour embolization). Circulating peptide levels were initially suppressed, but continued suppression did not occur in every case despite good clinical control. It seems likely that SMS 201-995 has beneficial effects on target organs as well as suppressing the release of peptides from tumour tissue. The tumours did not grow during treatment. The analogue was well tolerated, most adverse effects being minor. Somatostatin inhibited insulin release, but in only one patient was there a slight deterioration of glucose tolerance. SMS 201-995 is therefore a useful therapeutic tool in the long-term management of patients with symptoms due to uncontrolled hormone secretion from neuroendocrine tumours.

Adult↗
PubMed1986

Regulatory peptides of the gastrointestinal and respiratory tracts.

The gastrointestinal and respiratory tracts contain numerous regulatory peptides produced by and released from specialised epithelial cells and the organ innervation. This complex system of endocrine cells and nerves is generally called "the diffuse neuroendocrine system". Markers are now available which permit the visualisation of the diffuse neuroendocrine system or its individual components. These include antibodies to neuron-specific enolase, chromogranin, neurofilament triplet proteins, the brain protein S100 and antibodies to a variety of regulatory peptides. Peptides present in the gut and lung innervation include: vasoactive intestinal polypeptide (VIP), peptide histidine isoleucine (PHI), galanin, substance P, calcitonin gene-related peptide (CGRP), neuropeptide tyrosine (NPY), somatostatin and cholecystokinin (the latter two are also localised to endocrine cells of the gut). Bombesin-immunoreactivity is found in nerves in the gut and in endocrine cells of the foetal/neonatal lung. Neuropeptides of the gut and lung originate either from local neurons (e.g. VIP, PHI, galanin) or extrinsic neurons localised in sensory ganglia (e.g. substance P and CGRP) or the sympathetic chain (e.g. NPY). Recent studies point to the involvement of regulatory peptides in diseases of the gut and lung. These, together with detailed distribution studies, provide supportive data on the putative role of the peptides in the control of normal bowel and respiratory functions. The gastrointestinal and respiratory tracts were within the systems investigated by Feyrter during his original observations on the existence of specialised epithelial cells with a putative regulatory function (Feyrter, 1938). These "endocrine/paracrine" cells were found to be scattered in epithelial organs throughout the body. In fact, endocrine cells of the respiratory tract are frequently referred to as "Feyrter's cells". The term "regulatory peptides" was introduced as a generic term (Polak and Bloom, 1983) after the finding that active peptides are produced both by cells of the diffuse endocrine or APUD (amine precursor uptake and decarboxylation) system (Pearse, 1983) and autonomic/sensory nerves. These peptides are released into the circulation from endocrine cells or locally from nerve terminals or paracrine cells. The concept of "gut/brain" peptides was dispelled after the findings that the respiratory tract was provided abundantly with numerous active peptides produced by and released from mucosal endocrine cells and/or the innervation.

Animals↗
PubMed1986

The plasma atrial natriuretic peptide response to treatment of acute cardiac failure, spontaneous supraventricular tachycardia and induced re-entrant tachycardia in man.

Patients with acute congestive cardiac failure had elevated plasma concentrations of atrial natriuretic peptide (ANP) which fell towards normal levels with successful diuretic therapy. The plasma ANP concentration was closely correlated with the clinical condition of the patients as assessed by serial clinical measurement of the jugular venous pressure and body weight. Plasma ANP concentrations were also raised in patients with a spontaneous acute onset of supraventricular tachycardia but to a lesser extent in patients with chronic tachycardia. Again, successful treatment with d.c. cardioversion returned plasma ANP concentrations towards normal. Induction of atrioventricular re-entrant tachycardia produced an acute and marked rise in plasma ANP concentrations, which rapidly returned to normal when the sinus rhythm was restored. This acute ANP rise probably mediates the known acute natriuretic effect of paroxysmal tachycardia. All the data are consistent with the hypothesis that atrial distension, whatever the cause, releases ANP into plasma.

Adult↗
PubMed1986

The neuropeptide Y-immunoreactive neuronal system: discovery, anatomy and involvement in neurodegenerative disease.

The discovery of neuropeptides in mammalian nervous tissue has proceeded at an astonishing pace in recent years, encouraged by novel detection techniques which allow peptides to be extracted and sequenced before their biological activity has been determined (Mutt 1983; Sudcliffe et al. 1983). Most of these methods, poached from molecular biology, are nowadays reversing former trends which evolved either as a systematic search for factors known to control pituitary hormone release (vasopressin and oxytocin), for instance, or as an endeavour to find endogenous ligands for newly discovered receptors (the endorphins) (see Krieger 1983 for review). Neuropeptide tyrosine (NPY) has emerged as an important member of this new generation of peptides, not least because it is the most abundant and widely distributed in the mammalian brain. However, despite the considerable attention this peptide has attracted, we are far from understanding its functional significance. The following account traces the history of NPY and appraises some of the literature in an attempt to raise some speculation concerning its function; several reviews on this peptide already exist (Emson and de Quidt 1984; Solomon 1985; Allen and Bloom 1986; Gray and Morley 1986), Particular attention is paid to studies which have recently suggested that NPY might be involved with the pathogenesis of two neurodegenerative disorders, Huntington's chorea and Alzheimer's disease.

Alzheimer Disease↗
PubMed1986

Effect of soya bean oil on symptoms, gastric emptying and gut hormone release in patients with postvagotomy symptoms.

In a preliminary study the effect of an aperitif of a stable fat emulsion on symptoms, gastric emptying of a hypertonic glucose meal and associated release of insulin, neurotensin, enteroglucagon, gastric inhibitory polypeptide (GIP) and vasoactive intestinal polypeptide (VIP) was evaluated in 9 patients with postprandial gastrointestinal discomfort after vagotomy. In each patient gastric emptying of the glucose meal was measured twice: 20 min after intake of distilled water and after fat emulsion. On both occasions neurotensin, enteroglucagon and GIP rose significantly from fasting values. In contrast to distilled water, the fat emulsion was able to significantly activate the release of the hormones before ingestion of the glucose meal. All the patients had a rapid emptying of the glucose meal after distilled water and they experienced symptoms that corresponded with the nature of their spontaneous symptoms after ordinary meals. The fat emulsion reduced the early emptying of the meal and relieved the symptoms of the dumping patients, whereas gastric emptying and symptoms were variable in the patients with diarrhoea and other postvagotomy symptoms. The intake of an aperitif of soya bean oil seems to be an effective treatment only in patients with the dumping syndrome.

Adult↗
PubMed1986

Occurrence, distribution and origin of peptide-containing nerves of guinea-pig and rat male genitalia and the effects of denervation on sperm characteristics.

A systematic immunohistochemical and radio-immunological survey of the occurrence, distribution and origin of the peptidergic nerve supply in guinea-pig and rat male genitalia is presented. Neuropeptide Y (NPY), vasoactive intestinal polypeptide (VIP), peptide histidine isoleucine (PHI), substance P and CGRP were detected in the genital organs of both species. The densities and distribution patterns of the peptidergic nerves were compared with those of the adrenergic nerves, as revealed by antibodies raised against dopamine-beta-hydroxylase (D beta H) and tyrosine hydroxylase (TH), and the general neuronal component, as revealed by antibodies raised against neurofilament proteins (NF). Bilateral transection of the hypogastric nerves, in the guinea-pig, resulted in a decrease of substance P-containing nerves in the vas deferens and of NPY-, PHI- and VIP-containing nerves in the seminal vesicle. Unilateral disconnection of the pelvic nerves caused a decrease of VIP, PHI, substance P and CGRP nerve supply in the ipsilateral vas deferens and cauda epididymidis in the guinea-pig. A marked reduction of noradrenergic and NPY-containing nerves was observed in the vas deferens and sexual accessory glands of rats, chemically sympathectomised by chronic injection of low doses of guanethidine. Conversely, increase of substance P and CGRP immunoreactivities were observed, particularly in the vas deferens. After guanethidine, the cauda epididymidis and vas deferens were distended with spermatozoa, suggesting paralysis of the ducts. Spermatozoa had a decreased percentage of attached cytoplasmic droplets, indicating prolonged retention in the ducts.

Animals↗
PubMed1986

Cooperative regulation of neurotensin content in PC12 pheochromocytoma cell cultures: effects of nerve growth factor, dexamethasone, and activators of adenylate cyclase.

Nerve growth factor, dexamethasone, and forskolin or cholera toxin (CT) act cooperatively to increase the content of neurotensin (NT) in PC12 pheochromocytoma cells. Relatively small increases in NT content occur in the presence of NGF alone or dexamethasone alone, but not of forskolin or CT alone. Increases of 10- to 100-fold occur in the presence of NGF plus dexamethasone or NGF plus forskolin, and up to 600-fold increases occur in the presence of all three agents. These increases are extremely stable and persist for at least 2 weeks after removal of dexamethasone or forskolin. The complex regulation of NT stores in PC12 cells might reflect mechanisms that regulate NT content of normal chromaffin cells and/or neurons during development or in adult life. A small amount of stored NT is released in response to stimulation with 52 mM K+. This release is blocked in the presence of 2 mM Co2+, suggesting that it occurs via Ca2+-mediated exocytosis.

Adenylyl Cyclases↗
PubMed1985

Occurrence, distribution and nature of neuropeptide Y in the rat pancreas.

Significant quantities of a newly discovered peptide, neuropeptide Y, were found in the rat pancreas, where they were localized to nerves in the exocrine parenchyma and around arterial and ductal structures. Although unaffected by surgical parasympathectomy, the periarterial and periductal nerves were abolished by chemical sympathectomy, suggesting that NPY is partially costored with sympathetic transmitters in nerve fibers.

Animals↗
PubMed1985

Ontogeny of a novel pituitary protein (7B2) in the human fetal intestine.

The developmental profile of the concentration of a novel pituitary protein (7B2) was studied immunochemically in the human gastrointestinal tract from 12 weeks of gestation to 4 months after birth and was compared to the distribution in the adult. 7B2-like immunoreactivity (IR-7B2) was detected in all segments studied, but no gross changes were seen through fetal life. At term higher concentrations of IR-7B2 were found in the duodenum and the antrum, which is similar to the distribution of adult man. Gel permeation chromatography revealed that the main peak of 7B2 immunoreactivity in the fetal intestinal extract eluted with a Kav of 0.3. Similar elution profiles were also observed in extracts of human adult intestine.

Adult↗
PubMed1985

The effect of sympathectomy on calcitonin gene-related peptide levels in the rat trigeminovascular system.

The effect of sympathectomy on the calcitonin gene-related peptide (CGRP) level in the rat primary trigeminal sensory neurone was investigated. Six weeks after bilateral removal of the superior cervical ganglion there was a 70% rise in the CGRP content of the iris and the pial arteries, a 34% rise in the concentration in the trigeminal ganglion but no change in the brainstem. The CGRP rise in both end organs suggests that this phenomenon may be common to all peripheral organs receiving combined sensory and sympathetic innervations. The lack of any rise in the brainstem CGRP content raises the possibility that this process spares central terminations. In contrast, the level of neuropeptide Y, a peptide mainly contained in sympathetic terminals, fell to 35% of control values in the iris and pial arteries whilst the trigeminal ganglion and brainstem concentrations remained unchanged. The possible relevance of these observations to the clinical syndrome of postsympathectomy pain (sympathalgia) is discussed. There are similarities between the delayed onset of the human pain state and the delayed rise in sensory peptides after sympathectomy.

Animals↗
PubMed1985

Molecular forms of glucagon-like peptides in man.

Molecular forms of the glucagon-like peptides (GLP) encoded by the human preproglucagon gene were analysed by chromatography combined with specific radioimmunoassays to the synthetic peptides. Whereas extracts of human pancreas and a glucagonoma contained a large proglucagon cleavage product possessing both GLP-1 and GLP-2 immunoreactivities, extracts of human intestine contained products corresponding to free GLP-1 and a small amount of chromatographically distinct GLP-2 immunoreactivity. It is concluded that post-translational processing of proglucagon differs in pancreas and intestine, so that the C-terminal portion of the molecule is cleaved to liberate free GLP-1 in the intestine. Further processing or degradation results in loss especially of GLP-2 immunoreactivity.

Chromatography, High Pressure Liquid↗
PubMed1985

Production of "ectopic" vasoactive intestinal peptide-like immunoreactivity in normal human chromaffin cell cultures.

Vasoactive intestinal peptide-like immunoreactivity (VIPLI) is not detectable in normal adult human chromaffin cells in vivo, but was demonstrated in cultured chromaffin cells from two normal adults after 22 days in vitro. Cellular content of VIPLI was markedly increased in the presence of nerve growth factor, which also stimulated neurite outgrowth. Catecholamine content decreased in the same cultures, and was not regulated in parallel with VIPLI. The amounts of VIPLI in normal human chromaffin cells in culture are comparable to those previously reported in human pheochromocytoma cell cultures. Theoretical models have attributed production of ectopic peptides by pheochromocytomas and other tumors to "immaturity" of tumor cells. Our findings, however, indicate that neither neoplasia nor cellular immaturity is a prerequisite for ectopic peptide production. Ectopic neuropeptides produced by normal chromaffin cells which undergo neuronal differentiation are of potential clinical importance in patients receiving autologous chromaffin cell transplants for Parkinsons' disease.

Adrenal Medulla↗