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Biomedical subjects

S R Bloom

Publications and source records attributed to S R Bloom.

At least 469 records · Page 26Linked to original sources
PubMed1988

Decreased gastric acid secretion and bacterial colonization of the stomach in severely malnourished Bangladeshi children.

To assess the effect of malnutrition on gastric acidity and gastric bacterial colonization, we studied 35 severely malnourished Bangladeshi children before (0 wk) and after (3 wk) they received nutritional rehabilitation for 3 wk. These results were compared with those obtained from a similarly examined group of 20 better-nourished Bangladeshi children. Gastric acid output, both basal and after betazole stimulation, was significantly lower in the malnourished group at 0 wk compared with the better-nourished children (p less than 0.01): basal 0.22 vs. 0.52 mEq HCl/h and stimulated 0.90 vs. 2.5 mEq HCl/h. Both the concentration of acid and the rate at which gastric juice was secreted were decreased in the malnourished group but serum gastrin levels were not significantly different. After 3 wk, the malnourished children had improved from 61% (+/- 9.0%; SD) to 81% (+/- 8.1%) of expected weight-for-height and were not significantly different than the better-nourished group (86% +/- 11%). Nevertheless, gastric acid concentration remained depressed in the 3-wk group, although the rate of gastric juice secretion equaled levels observed in the better-nourished group. None of the better-nourished children had detectable gram-negative bacterial colonization of their gastric juice. In contrast, 26 of 32 (81%) malnourished children at 0 wk were colonized--even after betazole stimulation, 11 of 33 (33%) gastric juice samples yielded viable organisms--suggesting that the decrease in gastric acid output greatly reduced the gastric acid barrier. Interestingly, only 9 of 20 (45%) better-nourished children had gastric juice with basal pH values below 4.0, suggesting that the gastric acid barrier may be an intermittent defense factor in Bangladeshi children.

Age Factors↗
PubMed1988

Water content, vasoactive intestinal polypeptide and substance P in intact and crushed sciatic nerves of normal and streptozotocin-diabetic rats.

Observations on streptozotocin-diabetic rats have confirmed overhydration of peripheral nerve. As in previous studies, the sorbitol and fructose content, when expressed in terms of wet weight of nerve was found to be increased and myo-inositol decreased. The reduction in myo-inositol content was less, although still significant, when expressed in terms of protein content. Nerve water content increased during Wallerian degeneration following a crush injury in both normal and diabetic animals, but was relatively less in the latter. Vasoactive intestinal polypeptide (VIP) concentrations were significantly increased in diabetic nerve, those for substance P being normal. Both became severely reduced during Wallerian degeneration following nerve crush and ligature. The significance of these findings is discussed. The accumulation of water in the endoneurial compartment may be related to impaired extraction by the perineurium, to which the increased VIP content may contribute. These changes are unlikely to be responsible for nerve fibre damage.

Animals↗
PubMed1988

Increase in diazepam binding inhibitor-like immunoreactivity (51-70) in Huntington's disease.

In Huntington's disease (HD), reduction in striatal GABA is one of the most striking abnormalities and alterations in benzodiazepine receptors, which are allosterically linked to the GABAA receptor, have also been reported. Diazepam binding inhibitor (DBI), recently isolated from rat and human brain, has been proposed as an endogenous ligand at the benzodiazepine receptor. The content of DBI-like immunoreactivity(51-70) (DBI-IR(51-70), has therefore been compared in control postmortem human brains and in HD brains (matched for age, sex and post-mortem delay), using a specific radioimmunoassay. DBI-IR(51-70) was more than 1.5-fold increased in the putamen, caudate, globus pallidus and nucleus accumbens of HD brains compared to the control group (P less than 0.001). Gel filtration chromatography showed similar elution profiles of the peptide in both control and HD extracts, thus providing no evidence for a change in the nature of the peptide itself.

Aged↗
PubMed1988

The effect of cholinergic blockade on the growth hormone response to galanin in humans.

The effect of cholinergic blockade with pirenzepine or atropine on growth hormone (GH) release after galanin administration was investigated in five normal male subjects. The mean peak GH response to an infusion of galanin (40 pmol/kg/min for 40 minutes) was significantly reduced from 17.2 mU/L to 2.9 mU/L (P less than .001) with prior administration of pirenzepine (30 mg IV). When galanin was infused at a higher dose (80 pmol/kg/min), this suppression of release by pirenzepine was partially overcome, with GH rising to a mean peak response of 8.0 mU/L (P less than .05). Repeated administration of atropine (two bolus doses of 0.6 mg IV) also failed to abolish the GH response to this higher dose of galanin in two subjects. It has been proposed that cholinergic pathways control GH release via somatostatin, and this study suggests that galanin may also act by modulating hypothalamic somatostatinergic tone either directly or by facilitating cholinergic transmission.

Adult↗
PubMed1988

Plasma levels of 7B2 (a novel pituitary polypeptide) and its molecular forms in plasma and urine in patients with chronic renal failure: possible degradation by the kidney.

Plasma immunoreactive (IR)-7B2 was measured in patients with chronic renal failure (CRF), using a specific radioimmunoassay. The mean (+/- S.E.M.) concentration of plasma IR-7B2 in CRF patients under hemodialysis (502 +/- 36 pg/ml, n = 27) was significantly higher than that in normal subjects (men, 52.9 +/- 1.7 pg/ml (n = 179); women, 55.8 +/- 1.3 pg/ml (n = 198]. Significant correlations between plasma levels of IR-7B2 and those of blood urea nitrogen, creatinine and beta 2-microglobulin were evident in non-dialyzed CRF patients. In the analyses of pooled plasma and urine obtained from normal subjects on gel permeation chromatography, a major peak of IR-7B2 was observed at an apparent molecular weight of 20,000 in the plasma, and at a position of a smaller molecular weight in the urine. These results suggest that 7B2 is degraded mainly in the kidney and that measurement of plasma 7B2 may serve as an appropriate tool for assessing renal function.

Adult↗
PubMed1988

Age-related change in 7B2 (a novel pituitary polypeptide) concentrations in human cerebrospinal fluid.

Concentrations of 7B2 (a novel pituitary polypeptide) immunoreactivity (7B2-IR) were measured using a specific 7B2 radioimmunoassay (RIA) in cerebrospinal fluids (CSFs) from 87 humans. The mean (+/- S.E.M.) concentration of 7B2-IR in CSF was 2022 +/- 68 pM and a statistically significant decrease with aging was observed in those concentrations (R = -0.28, t = 2.73, P less than 0.01), although it was not a strong relation based on the R-value. In the gel permeation chromatography of CSF on Sephadex G-100, a major peak with an apparent mol. wt. of 43 kDa (43K) and a minor peak with that of 11 kDa (11K) were observed.

Aging↗
PubMed1988

Peptide histidine methionine (PHM) increases ileostomy output.

The human vasoactive intestinal peptide (VIP) gene also encodes peptides histidine methionine (PHM) which has substantial sequence homology with VIP. Both are present in nerve fibers in the human ileum and circulate in greatly increased concentrations in patients with the watery diarrhoea syndrome. We have infused PHM (23 pmol/kg/min) into 5 patients with ileostomies to determine the effect of PHM on human ileal output. Plasma PHM levels rose from 22 +/- 6 to 6013 +/- 874 pM (mean +/- S.E.M.) during PHM infusions and ileal output rose from 16 +/- 3 to 177 +/- 27 g/30 min (P less than 0.0001). PHM infusions also produced a significant fall in the percentage of solid material and a rise in the concentration of chloride in the ileal effluent. Mean plasma PHM concentrations during PHM infusions were equal to the highest levels seen in patients with the watery diarrhoea syndrome, so PHM may contribute to diarrhoea in this condition. Neuronal PHM may exert physiological control over ileal transport of water and electrolytes.

Chlorides↗
PubMed1988

Gastrin and somatostatin in the rat antrum. The effect of removal of acid-secreting mucosa.

Female rats were subjected to operations aimed at reducing the amount of oxyntic gland mucosa draining its acid secretion to the antrum. The rats were provided either with Heidenhain or Pavlov pouches reducing the oxyntic mucosa draining its secretion to the antrum by about 50% or subjected to various degrees (75, 90 and 100%) of fundectomy. Ten weeks following surgery, plasma levels of gastrin and somatostatin were assayed. At the same time, antral mucosal content of gastrin and somatostatin was determined as well as the mucosal density of these hormone-producing cells. There was a relationship between the amount of acid-secreting mucosa removed and the ensuring plasma concentration of gastrin. Thus, a stepwise increase in plasma gastrin was found with the highest levels obtained in rats subjected to 90 or 100% fundectomy. The somatostatin concentration in plasma was reduced only in rats subjected to fundectomy with the most sustained decrease in animals in which all oxyntic gland mucosa had been removed. There was also a relationship between the amount of acid-secreting mucosa removed and the gastrin content of the antral mucosa. An inverse relationship seemed to exist between antral gastrin and somatostatin concentrations. However, a significant decrease in somatostatin concentration of the antral mucosa was seen only in rats subjected to a fundectomy. The number of gastrin cells in the antral mucosa was increased in fundectomized rats only, with the largest density seen in rats deprived of all oxyntic mucosa. A corresponding decrease in the number of somatostatin cells was noticed. Our results would suggest an apparent functional relationship between antral gastrin and somatostatin cells, where the antral acid load (or pH) appears to be the major factor of physiological significance.

Animals↗
PubMed1988

Occurrence and developmental pattern of neuromedin U-immunoreactive nerves in the gastrointestinal tract and brain of the rat.

Neuromedin U is a newly described regulatory peptide, found by radioimmunoassay in significant concentrations in both the brain and gut of the rat. The aim of the present study was to localize this peptide immunoreactivity to discrete structures of the gut and brain and to map its distribution using immunocytochemistry. In the gut, neuromedin U was confined to nerve fibres mainly in the myenteric and submucous plexuses and the mucosa of all areas except stomach. Immunoreactive ganglion cells were seen in both ganglionated plexuses and their number did not increase following colchicine administration. This observation and the finding that the population of neuromedin U-immunoreactive nerves in the ileum was not affected by complete extrinsic denervation indicated that the nerves are mostly intrinsic in origin. Colocalization studies revealed neuromedin U and calcitonin gene-related peptide were present in the same myenteric and submucosal ganglion cells. Transection experiments showed that, like calcitonin gene-related peptide-immunoreactive nerves, fibres containing neuromedin U project for very short distances in both an oral and anal direction. At the electron microscopic level, neuromedin U immunoreactivity, demonstrated using the immunogold technique, was localized to large granular vesicles. In the central nervous system, neuromedin U immunoreactivity was localized to fibres which were widespread throughout the brain, except in the cerebellum. The presence of neuromedin U-immunoreactive cell bodies was restricted to the rostrocaudal part of the arcuate nucleus. Colocalization studies showed that a proportion of the neuromedin U-immunoreactive cell bodies in the arcuate nucleus also contained pro-opiomelanocortin. Neuromedin U-immunoreactive fibres were first detected in the rat intestinal mucosa at day 1 after birth. In the brain, the arcuate nucleus showed neuromedin U-immunoreactive neuronal cell bodies at E16 but not at E14. In conclusion, neuromedin U is a new member of the group of molecules known as brain-gut peptides.

Aging↗
PubMed1988

The distribution of melanin-concentrating hormone-like immunoreactivity in the central nervous system of rat, guinea-pig, pig and man.

The distribution of melanin-concentrating hormone-like immunoreactivity was investigated by radioimmunoassay in the CNS of rat, guinea-pig, pig and man. Highest concentrations of melanin-concentrating hormone-like immunoreactivity were found in the hypothalamus of all the species: rat 204.4 +/- 14.9; guinea-pig 159.5 +/- 23.3; pig 10.9 +/- 4.5 and man 80.1 +/- 19.1 pmol/g. Gel chromatographic analysis of hypothalamic extracts showed five immunoreactive peaks of melanin-concentrating hormone-like immunoreactivity in the rat and pig and six in the guinea-pig and man. High-performance liquid chromatography analysis of hypothalamic extracts showed five immunoreactive peaks in rat, guinea-pig, pig and four in man. However, these peaks appeared at different retention times from that of the single peak of salmon melanin-concentrating hormone. Examination of subcellular fractions of whole rat brain showed that most of the melanin-concentrating hormone-like immunoreactivity is found in the synaptosome fraction. Stimulation of melanin-concentrating hormone-like immunoreactivity release from rat hypothalamic slices revealed that potassium in the presence of calcium stimulated melanin-concentrating hormone-like immunoreactivity release. These findings suggest that mammalian melanin-concentrating hormone-like immunoreactivity has a different amino acid sequence from salmon melanin-concentrating hormone and may exist in multiple molecular forms. It is possible that melanin-concentrating hormone may play a role as a neurotransmitter or modulator in the mammalian CNS.

Adult↗
PubMed1988

Cerebellin-like peptide: tissue distribution in rat and guinea-pig and its release from rat cerebellum, hypothalamus and cerebellar synaptosomes in vitro.

We have developed a specific radioimmunoassay for "cerebellin", a 16-amino acid peptide recently isolated from rat cerebellum. In both rat and guinea-pig, cerebellin-like immunoreactivity was highest in the cerebellum but was also present in high concentrations elsewhere in the central nervous system, especially in the hypothalamus. In both species, cerebellin-like immunoreactivity was found in other organs (heart, kidney and stomach) and at lower concentrations in the gastrointestinal tract. In the brain of both species, cerebellin-like immunoreactivity consisted of a single molecular form with an elution position on gel filtration and high-performance liquid chromatography identical to that of synthetic rat cerebellin. However, peripheral tissue contained an additional immunoreactive peak of higher molecular weight. Cerebellin was concentrated in synaptosomal preparations of rat brain, and its subcellular distribution pattern in rat brain was identical to that of two other known synaptosomal peptides, vasoactive intestinal polypeptide and substance P. Studies with superfused cerebellar synaptosomes and slices of rat cerebellum and hypothalamus demonstrated calcium-dependent cerebellin release when stimulated by high potassium concentrations as well as the addition of the calcium ionophore A23187. Cerebellin has therefore a widespread distribution and fulfils two criteria for a neurotransmitter, in that it is found in brain synaptosomes and shows calcium dependent, depolarization-induced release from nervous tissues and isolated nerve endings. It may, therefore, be a component of a novel neurotransmitter system.

Animals↗
PubMed1988

The occurrence of pancreastatin in tumours of the diffuse neuroendocrine system.

We have reported previously the localization of the 49 amino acid peptide pancreastatin to all identifiable endocrine cells of porcine gut, pancreas and adrenal, thyroid and pituitary glands. In this study, we have investigated the occurrence of pancreastatin in a series of human neuroendocrine tumours using an antibody to whole synthetic porcine pancreastatin. The most consistent immunostaining for pancreastatin was found in carcinoid tumours of ileum (four out of six), rectum (four out of six), ovary (two out of two) and lung (nine out of 10). Radioimmunoassay of tumour extracts showed that the concentrations of pancreastatin in ileal carcinoids were very high (mean 71.6, range 31.0-184.0 pmol g-1). The high rate of positivity in lung carcinoids contrasted sharply with the results of 10 pulmonary small cell carcinomas which displayed no immunoreactivity and contained minimal concentrations of pancreastatin (mean 2.0, range 0-6.0 pmol g-1). Extra-adrenal paragangliomas also contained pancreastatin (seven out of 10), but although radioimmunoassay detected peptide in phaeochromocytomas (mean 29.8, range 8.0-69.0 pmol g-1), immunocytochemistry did not. Porcine pancreastatin shows structural homology with bovine chromogranin A, an observation which has led to suggestions that chromogranin is a precursor for the peptide. More recently, a sequence homologous to porcine pancreastatin has been identified in the human chromogranin A molecule. In this study, immunostaining with an antiserum to human chromogranin gave positive results in most cases of each tumour type except the small cell carcinomas. The lack of consistent relationships between chromogranin and pancreastatin immunoreactivities may reflect the fact that the antiserum to pancreastatin was raised against the porcine peptide. When antibodies to human pancreastatin become available, the peptide may prove to be a more consistent marker for neuroendocrine tumours.

Adenocarcinoma↗
PubMed1988

Does resection enhance the response of the intestine to urogastrone-epidermal growth factor in the rat?

1. The objective of this study was to see whether another proliferative stimulus could modify the marked proliferative effect of human epidermal growth factor (urogastrone-epidermal growth factor, URO-EGF) on the gastrointestinal epithelium. 2. The response of the gastrointestinal tract to URO-EGF was investigated in rats maintained on total parenteral nutrition (TPN) with or without 75% small bowel resection. 3. Continuous infusion of 60 micrograms of recombinant beta-urogastrone/day per rat increased proliferation in the stomach by over four times (P less than 0.01), doubled proliferation in the small intestine (P less than 0.001) and increased it by four and a half times in the colon (P less than 0.001) in the control group. No significant effect of urogastrone was observed in the stomach of the resected groups, but proliferation was also increased in the small intestine by one and a half times (P less than 0.001) and by nearly four times in the colon (P less than 0.001). 4. Two-way analysis of variance showed that resection had a significant effect (P less than 0.01) on proliferation below the anastomosis and in the ileum. However, the response of the ileum was only half that observed in orally fed rats, which confirms the importance of 'luminal nutrition' in the response to resection. 5. Intestinal resection in the TPN rat was associated with a small rise in plasma enteroglucagon levels, suggesting that this hormone may be implicated in the adaptive response of the small intestine to resection.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Potent and comparable vasodilator actions of A- and B-calcitonin-gene-related peptides on the superficial subcutaneous vasculature of man.

1. Vasoactivity of human A- and B-calcitonin-gene-related peptides was studied in normal subjects, using reflectance plethysmography to measure relative changes in blood flow produced by superficial subcutaneous injections of the peptides. 2. Injection of 10(-11) mol of either peptide caused an immediate 200% increase in local blood flow and prolonged hyperaemia lasting up to 3 h. The hyperaemic response to 10(-13) mol of each peptide was significantly (P less than 0.01) smaller and shorter in duration than that elicited by 10(-11) mol of the same peptide, and 10(-15) mol of both peptides produced no hyperaemia other than that attributable to needle insertion alone. 3. At all three dosages examined, there were no significant differences between A- and B-calcitonin-gene-related peptides in magnitude or time course of the hyperaemic response. 4. Human A- and B-calcitonin-gene-related peptides are therefore potent vasodilators in man, causing comparable dose-related vasodilatation in the superficial tissues.

Adolescent↗
PubMed1988

Postprandial glycaemic effects of a long-acting somatostatin analogue (octreotide) in non-insulin dependent diabetes mellitus.

Postprandial changes in blood glucose, insulin and glucagon were examined in 7 non-insulin dependent diabetic patients, before and after 3 days' treatment with the somatostatin analogue, octreotide (50 ug injected subcutaneously thricedaily). After octreotide injection, postprandial rises in plasma insulin and glucagon were significantly flattened. The postprandial glycaemic rise was delayed but the area under the glycaemic curve was not increased. Animal studies have suggested that octreotide inhibits growth hormone and glucagon secretion much more powerfully than native somatostatin, while relatively sparing insulin secretion. However, the present findings suggest that this analogue is not sufficiently selective to be therapeutically useful in non-insulin dependent diabetes.

Aged↗
PubMed1988

Reduced hypothalamic somatostatin and neuropeptide Y concentrations in the spontaneously-diabetic Chinese hamster.

Hypothalamic concentrations of six regulatory peptides having central effects on appetite and/or glucoregulation were measured by radioimmunoassay in spontaneously-diabetic Chinese hamsters and in age- and sex-matched non-diabetic control animals. In the diabetic hamsters, hypothalamic concentrations of somatostatin and neuropeptide Y were significantly reduced by 25-30% below controls. None of the other four peptides examined (bombesin, galanin, neurotensin and vasoactive intestinal peptide) differed significantly between the two groups. Disturbances in neuropeptide Y (the most potent central appetite stimulant yet discovered) and in somatostatin could be related to hyperphagia, an early and possibly primary abnormality of the diabetic syndrome in the Chinese hamster.

Animals↗
PubMed1988

Cloning, characterization, and sequence of a porcine cDNA encoding a secreted neuronal and endocrine protein.

This report describes the cloning, sequence, and characterization of a cDNA which encodes a protein synthesized in the brain and endocrine tissue, including pituitary, adrenal medulla, and ovary. The deduced 207-amino-acid sequence of the 23-kD protein contains a hydrophobic signal peptide suggesting that it is secreted. Northern blot analysis utilizing the cDNA clone identifies a single RNA of approximately 1400 nucleotides in porcine brain, adrenal medulla, pituitary, and ovary, as well as in human endocrine tumors. Very high levels of RNA were observed in one human pancreatic tumor. Southern blot analysis suggests that sequences homologous to the porcine cDNA are present in human, cow, rat, and salmon DNA, indicating that the gene(s) have been highly conserved during evolution.

Amino Acid Sequence↗