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Biomedical subjects

S R Bloom

Publications and source records attributed to S R Bloom.

At least 793 records · Page 44Linked to original sources
PubMed1984

Distribution and heterogeneity of immunoreactive cholecystokinin (CCK) in the mucosa of the porcine gastrointestinal tract.

The concentration and molecular nature of cholecystokinin-like immunoreactivity (CCK-LI) in extracts of porcine intestinal mucosa were determined using sequence-specific radioimmunoassays. Highest CCK concentrations were measured in duodenal mucosa (258 +/- 60 pmol/g in the distal duodenum) followed by jejunal mucosa (204 +/- 36 pmol/g in the proximal jejunum) and pylorus (51 +/- 9 pmol/g). All other gastrointestinal regions proximal to the pylorus and distal to the jejunum contained less than 20 pmol/g. Pancreas contained less than 1 pmol/g. Gel chromatography in 6 M urea revealed four immunoreactive forms and this was confirmed by reverse-phase high-pressure liquid chromatography (HPLC). The predominant molecular form in acid extracts of duodenal mucosa resembled CCK-33 although high concentrations of the larger CCK form ('CCK-58') and of the form intermediate in size between CCK-33 and CCK-8 were measured. A molecular form resembling CCK-8 was the principal form in neutral extracts of the duodenum.

Animals↗
PubMed1984

Regulatory peptides--the distribution of two newly discovered peptides: PHI and NPY.

PHI (peptide with histidine and isoleucine) and NPY (neuropeptide with tyrosine) are recently discovered regulatory peptides. There are close sequence similarities between PHI and both growth hormone releasing factor (GRF) and vasoactive intestinal polypeptide (VIP) and between NPY and pancreatic polypeptide. Using immunocytochemistry and radioimmunoassay we have revealed the broad distributions of PHI and NPY in neurons of the central nervous system and the majority of peripheral tissues. Tissues which are particularly well provided with these peptides include gut, pancreas, respiratory tract, skin and the genitourinary and cardiovascular systems. In most peripheral tissues, PHI-containing ganglion cells occur locally. NPY-containing fibres originate in part from cell bodies outside the tissues, in the sympathetic nervous system. Comparative studies indicate that PHI and VIP are co-stored in the same neurone and are identically distributed, thus suggesting the existence of a common precursor and subsequent gene duplication. The possible co-existence of catecholamines and NPY, suggested by the consistent finding of very similar distributions of the two substances, was investigated using antibodies to converting enzymes involved in catecholamine synthesis (tyrosine-hydroxylase and dopamine-beta-hydroxylase). The two enzymes and NPY were found together in at least part of the same neuronal system.

Animals↗
PubMed1984

Effect of peripheral nerve section and nerve crush on spinal cord neuropeptides in the rat; increased VIP and PHI in the dorsal horn.

An increase in vasoactive intestinal polypeptide (VIP) immunoreactivity in the dorsal lumbar hemisegment L4 of the spinal cord was observed by both radioimmunoassay and immunocytochemistry following sciatic nerve section or crush. Compared to the contralateral control hemisegment there was 125% and 35% more VIP immunoreactivity in the L4 hemisegment ipsilateral to the lesion 14 days following nerve section and crush respectively. The contralateral control hemisegment contained levels similar to L4 hemisegments from unoperated control rats. This increase appeared by immunocytochemistry to be confined to the substantia gelatinosa, in the region of termination of the majority of unmyelinated sciatic nerve afferents. Similar increases to VIP were observed for the peptide PHI, which is closely related to VIP. However, spinal cord substance P and somatostatin immunoreactivities were reduced following nerve section and unchanged following nerve crush whilst neurotensin and bombesin immunoreactivities were not affected following either lesion. Previous studies have shown that peripheral nerve injury produces a number of electrophysiological and biochemical changes in the dorsal horn of the spinal cord, including depletion of substance P in primary afferent neurones. The location of the cell bodies of fibres showing increased immunoreactivity remains to be established. Further studies are required to elucidate how these peptide changes are related to the adaptive processes which occur centrally following peripheral nerve injury.

Animals↗
PubMed1984

Slowly digested carbohydrate food improves impaired carbohydrate tolerance in patients with cirrhosis.

To test whether impaired carbohydrate tolerance in cirrhosis could be modified by dietary means ten cirrhotic patients, five of them taking insulin, took as breakfast either lentils or wholemeal bread and cottage cheese containing the same amount of carbohydrate and protein. Lentils resulted in significantly diminished blood glucose, insulin (in those not on insulin) and gastric inhibitory peptide responses. Enteroglucagon and neutrotensin levels were high with lentils, suggesting that absorption of lentil carbohydrate continued into the ileum with perhaps some malabsorption, so confirming the results of earlier studies in vitro. However, breath hydrogen studies on a separate group of eight healthy volunteers indicated that the difference in carbohydrate malabsorption between lentil, and wholemeal bread was insignificant. It is suggested that slowly digested carbohydrate foods, such as leguminous seeds, may minimize carbohydrate intolerance in patients with cirrhosis.

Blood Glucose↗
PubMed1984

Cloning, characterization, and DNA sequence of a human cDNA encoding neuropeptide tyrosine.

In vitro translation of the RNA isolated from a human pheochromocytoma demonstrated that this tumor contained a mRNA encoding a 10.5-kDa protein, which was immunoprecipitated with antiserum raised against porcine neuropeptide Y. Double-stranded cDNA was synthesized from total RNA and inserted into the Pst I site of pUC8. Transformants containing the neuropeptide Y cDNA were identified using the mixed hybridization probe d[A-(A,G)-(A,G)-T-T-(A,G,T)-A-T-(A,G)-T-A-(A,G)-T-G]. The probe sequences were based on the known amino acid sequence, His-Tyr-Ile-Asn-Leu, found in porcine neuropeptide Y. The nucleotide sequence of the cDNA was determined and contained 86 and 174 bases in the 5'- and 3'-untranslated regions, respectively. The coding sequence consisted of 291 bases, suggesting a precursor to neuropeptide Y that was 97 amino acids long (10,839 Da). The deduced amino acid sequence of the precursor suggested that there were at least two sites of proteolytic processing, which would generate three peptides having 28 (signal peptide), 36 (human neuropeptide Y), and 30 (COOH-terminal peptide) amino acid residues. A partial NH2-terminal sequence obtained by Edman degradation of the immunoprecipitated in vitro translation product identified the positions of methionine and leucine in the first 30 residues of the prepropeptide. A highly sensitive single-stranded complementary mRNA hybridization probe specific for neuropeptide Y mRNA was prepared using the bacteriophage SP6 promoter. This probe was used to identify a mRNA corresponding to neuropeptide Y of approximately 800 bases.

Adrenal Gland Neoplasms↗
PubMed1984

Corticotrophin releasing factor: effects on circulating gut and pancreatic peptides in man.

As a CRF-like peptide has been isolated from human gut, we investigated the effect of synthetic CRF-41 100 micrograms on gut and pancreatic peptides in six normal subjects. There was a significant rise in pancreatic polypeptide compared to a control infusion, but no change in plasma insulin, pancreatic glucagon, gastrin, somatostatin, motilin, neurotensin, gastric inhibitory peptide, or cholecystokinin was seen. In addition, there was no change in circulating met-enkephalin. We conclude that the rise in pancreatic polypeptide seen after CRF administration may suggest a role for a CRF-like peptide in the control of pancreatic function.

Adult↗
PubMed1984

The influence of adrenergic denervation on the response to feeding of the gastroenteropancreatic system in man.

The effect of adrenergic denervation on the metabolic and hormonal response to a standard meal was studied in six tetraplegic subjects (pre-ganglionic sympathectomy) and compared with six normal subjects. Gastric emptying, estimated by isotope scintiscanning, was similar in both groups. Following the meal the mean blood glucose and plasma insulin rose in both groups, but were higher and remained elevated for longer in the tetraplegic subjects. There were no significant differences in the secretion of pancreatic glucagon, enteroglucagon, gastric inhibitory peptide (GIP) and neurotensin between the two groups. The mean basal and post-prandial levels of pancreatic polypeptide and motilin were significantly higher in the tetraplegic group. This study confirms the presence of mild glucose intolerance in tetraplegic subjects which is not explicable on the basis of abnormal insulin or pancreatic glucagon secretion or abnormal gastric emptying. In addition the results provide evidence for a sympathetic inhibitory influence on the secretion of pancreatic polypeptide and motilin in man, which is probably adrenergically-mediated.

Adult↗
PubMed1984

Immunocytochemical localization of neuron specific enolase in small cell carcinomas and carcinoid tumours of the lung.

Carcinoid tumours and small cell carcinomas of the lung share many characteristics with normal neuroendocrine cells. While carcinoid tumours contain many dense-cored neurosecretory granules and are frequently argyrophil, small cell carcinomas are poorly granulated and rarely argyrophil, which casts doubt on their neuroendocrine nature. Immunostaining of the enzyme neuron specific enolase (NSE) was recently used to demonstrate the neuroendocrine components of the lung including nerves and neuroendocrine cells. We therefore used NSE immunostaining to investigate neuroendocrine differentiation in 79 lung tumours, including 18 bronchial carcinoids and 31 small cell carcinomas, and compared these results with those obtained with silver stains. Thirteen of the 18 carcinoids were reactive to silver, all other types being negative. NSE-immunoreactivity occurred in 16 carcinoids and 18 small cell carcinomas. None of the squamous cell carcinomas, large cell anaplastic carcinomas and adenocarcinomas examined showed NSE-immunoreactivity. Radioimmunoassay of extractable NSE from 10 fresh lung tumours correlated well with the immunostaining results, demonstrating large amounts in two small cell carcinomas (334 and 517 ng/mg protein) and three carcinoids (152, 908, and 1143 ng/mg protein). Values were much lower for four squamous cell carcinomas (31-44 ng/mg protein) and one large cell anaplastic carcinoma (30 ng/mg protein) and were accounted for by the presence of NSE-positive nerves and neuroendocrine cells in the surrounding lung. NSE immunostaining is a useful marker of neuroendocrine differentiation in lung tumours and should prove particularly valuable in the diagnosis of small cell anaplastic tumours and their metastases.

Carcinoid Tumor↗
PubMed1984

Serotonin receptor changes in dementia of the Alzheimer type.

Serotonin receptors were assessed in post-mortem brains of control and Alzheimer-type dementia (ATD) patients using ligand binding techniques. Differential losses of serotonin S1 and S2 receptors were present in neocortex, hippocampus, and amygdala of ATD patients, whereas no significant changes were observed in basal forebrain and basal ganglia. Losses of S1 receptors were significantly age-related in the ATD group, suggesting they occurred at a later stage of the disease process. Losses of S2 receptors were considerably greater (with a reduction to 35% of control in temporal cortex) and were not age-related in ATD. Significant correlations were observed within the ATD group between S2 receptor binding and somatostatin immunoreactivity in temporal and frontal cortices. Thus the loss of S2 receptors in ATD may be a relatively early change in the disease process, and may precede the changes in ascending serotonergic neurones.

Aged↗
PubMed1984

Neuroendocrine responses to stimulation of the splanchnic nerves in bursts in the conscious adrenalectomized calf.

Effects of stimulation of the peripheral ends of the splanchnic nerves below behavioural threshold at either 4 or 2 Hz continuously for 10 min, and at 40 or 20 Hz for 1 s at 10 s intervals for 10 min, have been compared in conscious calves. Cardiovascular responses were apparently unaffected by the pattern of the stimulus, whereas pancreatic neuroendocrine responses were significantly enhanced by stimulation in bursts, as was the rise in mean arterial plasma glucose concentration. Release of bombesin-like immunoreactivity was substantially potentiated by intermittent stimulation at relatively high frequencies and the significance of this discovery is discussed in relation to the effects that this peptide is known to evoke in this species.

Adrenalectomy↗
PubMed1984

Characteristics of the neuroendocrine responses to stimulation of the splanchnic nerves in bursts in the conscious calf.

Neuroendocrine responses to splanchnic nerve stimulation in bursts (at 40 Hz for 1 s at 10 s intervals for 10 min) have been investigated in conscious adrenalectomized calves, 3-6 weeks after birth, in the presence of various pharmacological blocking agents. Preganglionic blockade with hexamethonium abolished all the neuroendocrine responses that were monitored. Pre-treatment with phentolamine significantly reduced, but failed to eliminate, the release of both pancreatic glucagon and pancreatic polypeptide. In the presence of phentolamine splanchnic nerve stimulation produced a massive rise in arterial plasma insulin concentration. None of these pancreatic neuroendocrine responses was significantly affected by additional pre-treatment with propranolol. The rise in mean plasma insulin concentration which occurred in calves pre-treated with both phentolamine and propranolol was significantly reduced by atropine. Release of bombesin-like immunoreactivity (BLI) was unaffected by total post-ganglionic adrenergic and cholinergic blockade. The results indicate that pancreatic endocrine responses to splanchnic nerve stimulation may be attributable, at least in part, to release of BLI in this species.

Adrenalectomy↗
PubMed1984

Effects of certain metabolites on pancreatic endocrine responses to gastrin-releasing peptide in conscious calves.

The effects of intravenous infusions of synthetic gastrin-releasing peptide (GRP; 5 pmol/kg X min) have been investigated in 3- to 6-week-old conscious calves receiving continuous intravenous infusions of either glucose or amino acids or both at a dose of 0.03 mmol/kg X min and the results compared with the effects of the same dose of the peptide in control calves. Pre-treatment with amino acids alone caused a statistically significant fall in mean plasma glucose concentration, which was associated with a significant rise in mean pancreatic glucagon concentration. Additional infusion of glucose prevented this rise in plasma glucose concentration and resulted in a delayed, but very substantial rise in mean plasma insulin concentration. Pre-treatment with amino acids alone substantially and significantly increased the rise in mean plasma insulin that occurred in response to GRP. The rise in mean plasma glucagon concentration in response to GRP that occurred in the control group, the group pre-treated with amino acids alone and the group given both glucose and amino acids, was virtually eliminated in the group pre-treated with glucose alone. The normal rise in plasma pancreatic polypeptide concentration in response to GRP was invariably abolished in the presence of amino acids. No significant change in either mean neurotensin-like or gastric-inhibitory-peptide-like immunoreactivity was observed in response to GRP in any of these groups. The results are discussed in relation to possible physiological functions that GRP may subserve.

Amino Acids↗
PubMed1984

Haemodynamics of pelvic nerve induced penile erection in the dog: possible mediation by vasoactive intestinal polypeptide.

The haemodynamics of erection were elucidated in the anaesthetized dog by analysing in quantitative terms the changes of penile arterial inflow, venous outflow and tissue volume during graded pelvic nerve stimulation. The study also provides information on possible neurotransmitter mechanisms of the erectile response. Erection evoked by pelvic nerve stimulation appeared to result from two main circulatory events: first, there was a prompt dilatation of the penile 'resistance vessels', causing a greatly increased arterial inflow which in the early phase bypassed the cavernous bodies and, hence, increased venous outflow to the same extent. Secondly, the erectile response proper began after a distinct delay (approximately equal to 20 s). This was apparently caused by sudden opening of low resistance 'shunt vessels' diverting part of the arterial inflow into the cavernous bodies, leading to rapid filling. During the filling phase arterial inflow greatly exceeded venous outflow, and returned to the venous outflow level again in the steady state of full erection. The initial dilator response seemed to ensure rapid erection by establishing a high pressure head from the arterial microvessels to the cavernous spaces. The threshold frequency for the penile vasodilator response to pelvic nerve stimulation was 1-2 Hz and was always higher for the erectile volume response, viz. 2-4 Hz. Maximal effects for both were obtained at 16 Hz, causing on the average a 25-fold increase in peak arterial inflow, a 17-fold increase in venous outflow and a 107% increase in penile volume. Muscarinic blockade by atropine caused no significant decrease in the blood flow response induced by pelvic nerve stimulation, but clearly curtailed the erectile response. This indicates that the dilatation of the penile 'resistance vessels' is mainly non-cholinergic in nature, whereas a cholinergic mechanism seems to contribute to the erectile volume response proper. Pelvic nerve stimulation caused a substantial output of vasoactive intestinal polypeptide (VIP) from the penis which was correlated in onset and duration to the vasodilator response. Intra-arterial (I.A.) infusion of VIP elicited moderate erection and a penile vasodilator response which resembled the neural response. Similar effects were evoked by I.A. infusion of substance P, but the output of this peptide from the penis during stimulation was poorly correlated to the vascular events. These in vivo observations indicate that VIP might be the neurotransmitter responsible for the non-cholinergic pelvic nerve induced penile vasodilatation.

Animals↗
PubMed1984

Release of neuropeptide Y in response to splanchnic nerve stimulation in the conscious calf.

Plasma concentrations of neuropeptide Y were determined by means of a specific radioimmunoassay in the conscious calf. Significantly higher concentrations were found in the adrenal venous effluent (102 +/- 34 pmol/l) compared to systemic arterial plasma (11 +/- 7 pmol/l). Stimulation of the splanchnic nerves at 40 Hz in bursts for 1 s at 10 s intervals resulted in a slow sustained rise in plasma neuropeptide Y in both adrenal (peak 1124 +/- 217 pmol/l and peripheral (peak 771 +/- 182 pmol/l) samples. Experiments performed in adrenalectomized calves produced a closely similar release of neuropeptide Y when the nerves were stimulated intermittently in the same pattern and under the same conditions. Stimulation of the splanchnic nerves at 4 Hz continuously resulted in a smaller response. Pre-treatment with hexamethonium completely abolished the rise in plasma neuropeptide Y concentrations.

Adrenal Glands↗
PubMed1984

Vasoactive intestinal peptide concentrations and immunocytochemical studies in rectal biopsies from patients with inflammatory bowel disease.

Vasoactive intestinal polypeptide (VIP)-containing nerves and VIP content of endoscopic rectal biopsies from 47 patients with inflammatory bowel disease and 17 normal controls were examined by immunocytochemistry and radioimmunoassay. Immunocytochemistry revealed a consistent increase in, and abnormal appearance of, VIP nerves in patients with Crohn's disease not only those with rectal involvement but also patients with no histological evidence of rectal disease. Normal control biopsies contained 1.64 +/- 0.39 pmol VIP/mg protein as compared with 3.43 +/- 1.24 pmol VIP/mg protein in tissue from patients with rectal Crohn's disease and 5.37 +/- 1.23 pmol VIP/mg protein in those with Crohn's disease without rectal involvement. Ten of the 17 biopsies examined from ulcerative colitics showed a normal pattern of VIP innervation. Examination of the conventional histology of these biopsies showed that only areas with obvious active proctitis had increased VIP nerves and, unlike the appearance in Crohn's disease, these nerves had a normal morphology. The VIP content of these biopsies was similar to that of the controls; 1.34 +/- 0.37 pmol/mg protein.

Adolescent↗
PubMed1984

The ileal brake--inhibition of jejunal motility after ileal fat perfusion in man.

The possibility that malabsorbed fat passing through the human ileum exerts an inhibitory feedback control on jejunal motility has been investigated in 24 normal subjects by perfusing the ileum with a fat containing solution designed to produce ileal luminal fat concentrations similar to those in steatorrhoea (30-40 mg/ml). Mean transit times through a 30 cm saline perfused jejunal segment were measured by a dye dilution technique. Thirty minutes after ileal fat perfusion, mean transit times rose markedly to 18.9 +/- 2.5 minutes from a control value of 7.5 +/- 0.9 minutes (n = 5; p less than 0.05). This was associated with an increase in volume of the perfused segment which rose to 175.1 +/- 22.9 ml (control 97.6 +/- 10.3 ml, n = 5; p less than 0.05). Transit times and segmental volumes had returned towards basal values 90 minutes after completing the fat perfusion. Further studies showed that ileal fat perfusion produced a pronounced inhibition of jejunal pressure wave activity, percentage duration of activity falling from a control level of 40.3 +/- 5.0% to 14.9 +/- 2.8% in the hour after ileal perfusion (p less than 0.01). Ileal fat perfusion was associated with marked rises in plasma enteroglucagon and neurotensin, the peak values (218 +/- 37 and 68 +/- 13.1 pmol/l) being comparable with those observed postprandially in coeliac disease. These observations show the existence in man of an inhibitory intestinal control mechanism, whereby ileal fat perfusion inhibits jejunal motility and delays caudal transit of jejunal contents.

Adult↗