Search PubMed⌕ Search

Biomedical subjects

S R Bloom

Publications and source records attributed to S R Bloom.

At least 613 records · Page 34Linked to original sources
PubMed1986

Peptide YY abnormalities in gastrointestinal diseases.

Plasma concentrations of peptide YY (PYY), a newly isolated peptide produced by ileal and colonic endocrine cells, were measured in several groups of patients with digestive disorders after a standardized normal breakfast. Peptide YY levels were found to be grossly elevated in patients with steatorrhea due to small intestinal mucosal atrophy (tropical sprue). Basal levels in these patients were 79 +/- 18 pM, which was nearly 10-fold higher than those seen in healthy controls (8.5 +/- 0.8 pM). Patients with steatorrhea due to chronic destructive pancreatitis also had substantially increased basal PYY levels (47.5 +/- 6.3 pM), and their postprandial response was also greater than that of normal subjects. Moderately elevated plasma PYY concentrations were seen in patients with inflammatory bowel disease and patients recovering from acute infective diarrhea. In contrast, patients with diverticular disease, duodenal ulcer, and functional bowel disease had normal PYY responses. These changes in the secretion of PYY responses. These changes in the secretion, may shed light on the physiologic role of this newly discovered peptide and on intestinal adaptation to common digestive disorders.

Adult↗
PubMed1986

NPY stimulates nett absorption across rat intestinal mucosa in vivo.

NPY is a peptide recently isolated from porcine brain which has been seen to be widely distributed in the central and peripheral nervous system. The peptide is known to be present in substantial quantities in the extrinsic and intrinsic innervation of the gut but few studies have yet been done on the functional activity of the peptide in this site. In this study, intravenous infusion of porcine NPY was seen to cause nett absorption in the proximal duodenum. In addition, NPY was found to inhibit the nett secretory effect of simultaneously infused VIP in the proximal duodenum and jejunum. This evidence of functional activity of NPY in the gut further supports a role for this peptide in controlling or modulating intestinal function.

Animals↗
PubMed1986

Capsaicin induces a depletion of calcitonin gene-related peptide (CGRP)-immunoreactive nerves in the cardiovascular system of the guinea pig and rat.

We have demonstrated that calcitonin gene-related peptide (CGRP) immunoreactivity is widely distributed in cardiac and perivascular nerves of the guinea pig and rat. In the guinea pig the number and distribution of CGRP-immunoreactive nerve fibres closely paralleled that of fibres containing substance P, the two immunoreactivities being found invariably to coexist in the same perivascular networks and terminals. In the rat, CGRP-immunoreactive cardiovascular nerves had a similar distribution to those containing substance P, but in contrast to the guinea pig the former were far more numerous. Marked regional variations were observed in the density of the CGRP-immunoreactive innervation in both species. The CGRP-immunoreactive content of tissue extracts was in close agreement with the immunocytochemical findings, the highest levels of CGRP occurring in the mesenteric artery (guinea pig and rat) and inferior vena cava (guinea pig). Following capsaicin treatment of adult guinea pigs and neonatal rats, there was a significant loss of CGRP-immunoreactive nerves in the two species. In the guinea pig, substance P-and CGRP-immunostained fibres were depleted to a similar extent, throughout the cardiovascular system. However, the loss of rat CGRP-immunoreactive nerves was dose-dependent and displayed considerable variation, some perivascular nerve networks appearing less susceptible than others to the action of capsaicin. The results suggest that there may be species differences in the sensitivity of CGRP-containing nerves to capsaicin treatment, but at least the majority of CGRP-immunoreactive cardiovascular nerves may be presumed to be sensory in origin.

Animals↗
PubMed1986

Calcitonin gene-related peptide immunoreactivity in afferent neurons supplying the urinary tract: combined retrograde tracing and immunohistochemistry.

The innervation of rat and guinea pig urinary tract was examined using immunohistochemistry, radioimmunoassay and True Blue retrograde tracing techniques and was further assessed following both surgical and chemical denervation experiments. Substantial amounts of calcitonin gene-related peptide-like immunoreactivity (range 20-150 pmol/g) were detected in tissue extracts and localised to nerve fibres distributed throughout the urinary tract of both species, these being concentrated in the ureter and base of the bladder. In the guinea pig, the number and distribution pattern of calcitonin gene-related peptide-like immunoreactive nerves appeared to be identical to that of substance P-containing nerves, whereas in the rat the former predominated. Seven days after injection of the fluorescent dye True Blue into tissues of the urinary tract, retrogradely labelled cells were found in the dorsal root ganglia. These cells had a segmental distribution pattern which was specific for each of the injection sites. Thus, after injection of True Blue into the left kidney hilum a single group of labelled cells were found in the ipsilateral T10-L2 dorsal root ganglia. In contrast, injection into the left ureter produced labelled cells in two separate groups of ipsilateral ganglia (T11-L3 and L6-S1). Injection into the wall of the bladder and upper urethra resulted in bilateral labelling, with most labelled cells occurring in L6 and S1 ganglia. Approximately 90% of labelled cells in T10-L3 dorsal root ganglia displayed calcitonin gene-related peptide-like immunoreactivity, but only 60% of retrogradely labelled bladder neurons in L6-S1 ganglia were immunoreactive for this peptide. Adult guinea pigs and neonatal rats injected systemically with capsaicin subsequently exhibited a marked reduction both in the amount of calcitonin gene-related peptide immunostaining and the concentration of immunoreactive material in the urinary tract, dorsal root ganglia and spinal cord. In rats treated neonatally with capsaicin, there was a significant reduction in the number of retrogradely labelled cells and a hypertrophy of the bladder. Sectioning of the pelvic and hypogastric nerves in the rat also resulted in a depletion of calcitonin gene-related peptide-like immunoreactive nerves in the bladder, whereas chemical sympathectomy appeared to have no effect. The results indicate that calcitonin gene-related peptide immunoreactivity occurs in a major proportion of afferent neurons supplying the urinary tract of the rat and guinea pig.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1986

The effect of 6-hydroxydopamine, reserpine and cold stress on the neuropeptide Y content of the rat central nervous system.

Neuropeptide Y has previously been detected in neurons throughout the rat brain and spinal cord. On histochemical grounds, the neuropeptide Y-containing cell bodies have been subdivided into two groups: those in the brain stem in which colocalization with noradrenaline and adrenaline has been demonstrated and those in other brain regions where no catecholamine coexistence is found. In this paper the regional distribution of neuropeptide Y has been investigated in the rat brain by a specific neuropeptide Y radioimmunoassay, before and after the destruction of catecholaminergic nerve terminals by the administration of intraventricular 6-hydroxydopamine. Despite massive reductions in brain catecholamines, the neuropeptide Y level was unchanged in the cerebral cortex, striatum, spinal cord and hippocampus. A minor reduction in neuropeptide Y was found in the hypothalamus. Reserpine treatment, which is known to deplete brain nerve terminal stores of catecholamines, likewise did not result in any loss of neuropeptide Y. Cold stress which increases noradrenergic turnover in the rat brain stem had no effect on neuropeptide Y levels. These results suggest that the bulk of neuropeptide Y in the rat brain and spinal cord may not be stored in catecholaminergic nerve terminals.

Animals↗
PubMed1986

Effect of reserpine, phenoxybenzamine and cold stress on the neuropeptide Y content of the rat peripheral nervous system.

The effect of reserpine treatment on the neuropeptide Y content of the rat adrenal gland, heart, kidney and vasculature was studied using a specific radioimmunoassay. One hour after reserpine administration (5 mg/kg) the neuropeptide Y concentration in the adrenal gland was significantly reduced and after 4 h a similar reduction was seen in the heart and kidney. After 48 h, neuropeptide Y concentrations were reduced in all tissues. The greatest reduction occurred in the cardiac septum (77%) and the least in the inferior vena cava (25%). Phenoxybenzamine (2 mg/kg) also caused a reduction in neuropeptide Y concentrations which was less marked than after reserpine, except in the adrenal gland where it was similar. Cold stress caused no change in neuropeptide Y concentrations. The neuropeptide Y depletion induced by reserpine was compared to that following 6-hydroxydopamine. In the heart and pial arteries both drugs caused a similar neuropeptide Y depletion whilst in the pineal gland and renal artery 6-hydroxydopamine had more effect than reserpine. The implications of these results on NPY storage sites are discussed.

Animals↗
PubMed1986

Occurrence, distribution and ontogeny of CGRP immunoreactivity in the rat lower respiratory tract: effect of capsaicin treatment and surgical denervations.

The occurrence and distribution of calcitonin gene-related peptide (CGRP) immunoreactivity in the rat respiratory tract were investigated by means of immunocytochemistry and radioimmunoassay using antibodies raised in rabbits to synthetic rat CGRP. Substantial amounts of CGRP immunoreactivity (range 5-37 pmol/g) were detected in all parts of the respiratory tract, the highest being in the stem bronchus. Gel filtration chromatography of extractable CGRP immunoreactivity revealed one single peak, eluting at the position of synthetic rat CGRP. CGRP immunoreactivity was localized both in mucosal endocrine cells and nerve fibres from the larynx down to the peripheral lung. CGRP-immunoreactive endocrine cells were found singly in trachea and stem bronchi and in groups in intrapulmonary airways. They appeared at a late stage of gestation (17 days), reached a maximum number near term and decreased after birth to maintain a population similar to that of the adult animals by postnatal day 21. Similarly, CGRP-immunoreactive nerve fibres were first identified by day 18 of the gestation period and reached the adult distribution by postnatal day 21. CGRP-immunoreactive nerve fibres were localized among smooth muscle, seromucous glands, beneath and within the epithelium of the airways and around blood vessels. CGRP was also found in sensory ganglia and in motor end plates of the larynx musculature. Neonatal pretreatment with capsaicin caused a marked reduction in CGRP immunoreactivity of nerve fibres in the respiratory tracts as well as a less marked decrease in the population of CGRP-containing endocrine cells of the lung. No change was seen in motor end plates immunostaining. Vagal ligation experiments revealed that CGRP-immunoreactive nerve fibres travelling in the vagus originate mainly from neurons located in the jugular ganglion. Infranodosal right vagal ligation induced a marked loss in CGRP-immunoreactive nerves of the trachea, and of the ipsilateral stem bronchus, but no changes were observed in peripheral lung. By contrast infranodosal left side vagal ligation caused a decrease in CGRP-immunoreactive nerves of the ipsilateral lung and bronchus without affecting the peptide content in the trachea. Left vagal ligation also induced a marked increase in both the intensity of staining and number of CGRP-immunoreactive endocrine cells in the lung. We conclude that CGRP immunoreactivity is localized in both nerve fibres and endocrine cells and is associated principally with the afferent (sensory) innervation of the respiratory tract.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1986

Regional cerebral glucose transport in insulin-dependent diabetic patients studied using [11C]3-O-methyl-D-glucose and positron emission tomography.

Regional cerebral [11C]3-O-methyl-D-glucose ([11C]MeG) uptake kinetics have been measured in five insulin-dependent diabetic patients and four normal controls using positron emission tomography (PET). Concomitant measurement of regional cerebral blood volume and CBF enabled corrections for the presence of intravascular [11C]MeG signal in cerebral regions of interest to be carried out, and regional cerebral [11C]MeG unidirectional extraction fractions to be computed. Four of the five diabetic subjects were studied with their fasting plasma glucose level clamped at a normoglycaemic level (4 mM), and four were studied at hyperglycaemic plasma glucose levels (mean 13 mM). The four diabetic subjects whose fasting plasma glucose levels were clamped at a normoglycaemic level of 4 mM had mean fasting whole-brain, cortical, and white matter [11C]MeG extraction fractions of 15, 15, and 16%, respectively, values similar to those found for the four normal controls (whole brain, 14%; cortex, 13%; white matter, 17%). Mean regional cerebral [11C]MeG extraction fractions were significantly reduced in diabetic subjects during hyperglycaemia whether their plasma insulin levels were undetectable or whether they were raised by continuous intravenous insulin infusion. Such a reduction in [11C]MeG extraction under hyperglycaemic conditions can be explained entirely in terms of increased competition between [11C]MeG and D-glucose for the passive facilitated transport carrier system for hexoses across the blood-brain barrier (BBB). It is concluded that the number and affinity of D-glucose carriers present in the BBB are within normal limits in treated insulin-dependent diabetic subjects. In addition, insulin appears to have no effect on the transport of D-glucose across the BBB.

3-O-Methylglucose↗
PubMed1986

Neuropeptide Y in renovascular models of hypertension in the rat.

Neuropeptide Y content of the kidneys, heart, blood vessels, adrenals and brain stem was determined in both two-kidney, one-clip and one-kidney, one-clip Goldblatt hypertension in rats and compared with levels in age- and sex-matched controls. Renal neuropeptide Y content was significantly reduced in the clipped kidney of rats in both Goldblatt two-kidney, one-clip and Goldblatt one-kidney, one-clip models of hypertension. The content of neuropeptide Y was also reduced but to a lesser extent in the contralateral, non-ischaemic kidney in the two-kidney, one-clip model. In both models of hypertension, neuropeptide Y content in the heart was significantly reduced in the left ventricle and septum but unchanged in the atria and right ventricle wall. There was no significant change in the concentration of neuropeptide Y through the vasculature (major arteries and veins), including the renal artery distal to the clip, or in adrenals and brain stem.

Adrenal Glands↗
PubMed1986

Atrial natriuretic peptide inhibits the aldosterone response to angiotensin II in man.

We have investigated the interaction between the recently discovered natriuretic factor alpha human atrial natriuretic peptide (alpha h-ANP) and the renin-angiotensin-aldosterone system in man. Angiotensin II infused with placebo produced a significant rise of plasma aldosterone concentration (mean +/- SEM increment 352 +/- 23 pmol/l, n = 7, P less than 0.001). The infusion of alpha h-ANP together with angiotensin II largely abolished the aldosterone response (P less than 0.001). Diastolic blood pressure rose in response to the infusion of angiotensin II with placebo (mean increment 21.0 +/- 0.9 mmHg, P less than 0.001). Systolic blood pressure increased to a lesser degree (mean increment 12.5 +/- 0.7 mmHg, P less than 0.001). The infusion of alpha h-ANP together with angiotensin II significantly blunted the diastolic pressor response (P less than 0.01). This ability of alpha h-ANP to blunt the pressor effect of angiotensin II may be important in the control of systemic blood pressure. The inhibition of angiotensin II-stimulated aldosterone release demonstrates that alpha h-ANP may not only be a circulating natriuretic factor in its own right but that it may also act as a modulator of a related endocrine system.

Adult↗
PubMed1986

The plasma release of atrial natriuretic peptide in man.

We studied plasma atrial natriuretic peptide (ANP) concentrations in seven normal subjects after the acute intravenous infusion of sodium chloride/potassium chloride solution (saline). Three separate infusions of 6, 12 and 18 ml of saline/kg body weight each significantly increased the circulating concentration of ANP without changes of plasma osmolality or electrolyte concentrations. The mean maximal rise of the plasma ANP concentration after the three saline infusions was significantly correlated (r = 0.74, P less than 0.001) with, but occurred 10-30 min later than, the maximal atrial pressure rise. These observations are in accord with the hypotheses that: (a) ANP is a circulating natriuretic factor; (b) atrial distension is an important stimulus to ANP release in man.

Adolescent↗
PubMed1986

Atrial natriuretic peptide: physiological release associated with natriuresis during water immersion in man.

Thermoneutral water immersion produces a physiological increase of thoracic blood volume, raises central venous pressure and increases urinary sodium excretion by a hitherto ill-understood mechanism. We have investigated whether this enhanced sodium excretion could be mediated by the recently discovered natriuretic factor, atrial natriuretic peptide (ANP). During water immersion there was a highly significant (P less than 0.001) twofold increase of the mean plasma ANP concentration and a doubling of the mean urinary sodium excretion. Both were unchanged during the control experiments. These results are consistent with the hypotheses that ANP is released into plasma in response to central blood volume expansion and that it functions as a natriuretic hormone in normal man under physiological conditions.

Adult↗
PubMed1986

Immunocytochemical characterization of 10 pancreatic tumours, associated with the glucagonoma syndrome, using antibodies to separate regions of the pro-glucagon molecule and other neuroendocrine markers.

Histological diagnosis of neuroendocrine tumours can be hampered by their lack of peptide or amine immunoreactivity. In order to assess the usefulness of a range of specific and general markers of neuroendocrine differentiation, 10 pancreatic endocrine tumours, associated with high levels of circulating glucagon, were studied using histology, histochemistry, immunocytochemistry and electron microscopy. All cases showed immunoreactivity for one or other of the peptides derived from pro-glucagon, although only seven were found to contain immunoreactive pancreatic glucagon. The presence of secretory granules in eight of the tumours was demonstrated by electron microscopy, argyrophilia or chromogranin immunoreactivity. Not only was neuron specific enolase positively immunostained in all the tumours, thereby revealing their neuroendocrine nature, but also the intensity of the immunostain was higher in four of the five malignant ones than in the rest of the cases. Pancreatic polypeptide was present in non-glucagon cells in six out of 10 cases. Our results emphasize the importance of the use, not only of general histochemical and immunocytochemical tests but also antibodies to all possible derivatives of the precursor form of the active tumour product in the diagnosis of possible endocrine tumours. In this way, any abnormal molecular forms of the peptide synthesized by tumour cells with altered synthetic and secretory mechanisms may be detected.

Adenoma, Islet Cell↗
PubMed1986

An investigation of the use of high- and low-preference food as a reinforcer for increased activity of individuals with Prader-Willi syndrome.

The results of this study provide information that might be used to develop an approach to weight loss management for individuals with Prader-Willi syndrome that emphasizes the increase of output. Specifically, our finding that they do have a definite food preference and, subsequently, that they prefer a lesser amount of the high-preference food than a greater amount of low-preference food is contradictory to several non-empirical reports (Holm, 1981; Pipes & Holm, 1981). Further, the use of food as a reinforcer has been considered taboo by those who use more conventional and restrictive management approaches with Prader-Willi syndrome individuals. Our data, however, strongly suggest that a low volume of food can be used as an effective reinforcer for increased activity and exercise.

Adolescent↗
PubMed1986

Objective responses to ketoconazole therapy in patients with relapsed progressive prostatic cancer.

The contribution of adrenal androgens to the maintenance and progression of so-called hormone-unresponsive prostatic carcinoma was studied in 20 patients with advanced relapsed disease. The role played by testicular androgens had been negated by prior orchiectomy or concurrent LHRH analogue therapy. Ketoconazole, an antifungal agent which inhibits adrenal and testicular androgenesis, administered in a dose of 400 mg 8-hourly, resulted in optimal suppression of adrenal androgens. The mean serum androstenedione concentration fell from 8.01 +/- 0.84 nMol/l to 1.55 +/- 0.25 nMol/l, P less than 0.001, and serum testosterone from 1.25 +/- 0.14 nMol/l to 0.36 +/- 0.06 nMol/l, P less than 0.01, after 6 months treatment. There was, however, no significant difference between patients receiving 400 and those receiving 200 mg. Androgen suppression resulted in six objective and ten subjective clinical responses. Ablation of both testicular and adrenal androgens can now be achieved using ketoconazole in combination with orchiectomy or LHRH analogues, but the high incidence of side effects may preclude its use in all patients with prostatic cancer. The results of this study support the concept of "total androgen ablation" as primary therapy in advanced prostatic cancer as a possible means of improving survival in this common malignancy.

Acid Phosphatase↗
PubMed1986

Long-term effects of intestinal alpha-glucosidase inhibition on postprandial glucose, pancreatic and gut hormone responses and fasting serum lipids in diabetics on sulphonylureas.

Seventeen non-insulin-dependent diabetics poorly controlled by diet and sulphonylurea drugs took part in a long-term (20-52 weeks) trial of the effect of an alpha-glucosidase inhibitor (acarbose 100 mg thrice daily) on postprandial glycaemic and gastro-entero-pancreatic hormone responses. Patients were assessed before, during, and after the trial period with identical 2.2 MJ mixed test meals plus placebo or acarbose 100 mg, and sulphonylurea therapy was continued throughout. Acarbose administration reduced the integrated postprandial plasma responses of glucose to 58 +/- 10% (mean +/- SEM, p less than 0.001), insulin to 61 +/- 10% (p less than 0.01) and gastric inhibitory polypeptide to 45 +/- 8% (p less than 0.001) of control values, increased the enteroglucagon response to 152 +/- 26% (p less than 0.001) of control and slightly prolonged the postprandial release of motilin. Recorded glycosuria was significantly (p less than 0.01) reduced throughout the treatment period. The effects of acarbose on postprandial glycaemic and endocrine responses remained approximately constant throughout the trial period, and responses returned to pre-treatment values within 2 days of stopping treatment.

Acarbose↗
PubMed1986

Gut hormones and 'minimal enteral feeding'.

Previously we have identified multiple surges in plasma concentrations of gut hormones postnatally in enterally fed term and preterm infants. In this study on 104 preterm infants we have shown that such surges are induced after ingestion of very small quantities of human milk. Whereas 6-day-old exclusively parenterally fed infants showed no postnatal elevation in enteroglucagon, gastrin, GIP, motilin and neurotensin, infants recovering from hyaline membrane disease who had received restricted enteral nutrition had similar hormone surges to those seen in well infants on full enteral feeds. Significant elevations in enteroglucagon, gastrin and GIP occurred after a cumulative mean enteral feed volume since birth of only 24 ml (12 ml/kg body weight) had been consumed and after a mean total intake of 96 ml (50 ml/kg) the response was maximal. Greater feed volumes were required to produce a neurotensin or motilin surge, but even these volumes were substantially lower than those required for full enteral feeding. In view of the proposed roles of gut hormones in the adaptation to extrauterine nutrition these data have implications for mammalian biology and raise the possibility that 'minimal enteral feeding' might have a clinical therapeutic role in infants undergoing prolonged parenteral nutrition.

Enteral Nutrition↗