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Biomedical subjects

S R Bloom

Publications and source records attributed to S R Bloom.

At least 559 records · Page 31Linked to original sources
PubMed1987

Studies on intracavernosal VIP levels during pharmacologically induced penile erections.

Intracavernosal and peripheral venous vasoactive intestinal polypeptide (VIP) levels were measured in men with predominantly organic or predominantly psychogenic impotence. The measurements were taken at intervals up to 30 min following intracavernosal injections of saline, papaverine hydrochloride and papaverine hydrochloride and phentolamine. Levels were also measured after tactile and visual sexual stimulation and following an intravenous injection of papaverine and phentolamine. A penile erection occurred in all men receiving intracavernosal vasoactive compounds. The mean VIP concentration did not alter significantly in either cavernosal or peripheral venous blood during the erection. Mean VIP concentrations were significantly greater in the neurogenic (all diabetic) group than in the other groups studied. Mean cavernosal and peripheral VIP concentrations did not alter following tactile or visual sexual stimulation and no significant alteration in mean peripheral venous VIP concentration occurred following injection of papaverine and phentolamine. The putative role of VIP in the induction of penile erection has not been elucidated in these studies.

Erectile Dysfunction↗
PubMed1987

Calcitonin gene-related peptide is localised to human airway nerves and potently constricts human airway smooth muscle.

In human airways synthetic human sequence calcitonin gene-related peptide (hCGRP), a novel peptide produced by alternative processing of mRNA from the calcitonin gene, caused concentration-dependent contraction of human bronchi (EC50 4.9 X 10(-9) M) and was significantly more potent than substance P or carbachol. The contractile response was unaffected by atropine (2 X 10(-6) M), propranolol (10(-6) M), indomethacin (10(-5) M), tetrodotoxin (3 X 10(-6) M), chlorpheniramine (10(-4) M), cimetidine (10(-5) M), or FPL55712 (10(-4) M) suggesting a direct effect of CGRP on airways smooth muscle. CGRP was detected in human airways by radioimmunoassay with highest concentrations in cartilaginous airways. CGRP was localised by immunocytochemistry to both nerves and ganglia in human airways. CGRP, is a potent constrictor of human airways and may have important effects on airway function and be implicated in the pathogenesis of bronchial hyper-responsiveness and asthma.

Aged↗
PubMed1987

Motilin secretion and the migrating myoelectric complex in the pig.

The concentration of motilin in plasma from the abdominal aorta and the hepatic portal vein and the net portal motilin output varied with the phase of the migrating myoelectric complex (m.m.c.) in five of six pigs fasted for 17 h. Maximum concentrations and output occurred 9-12 min before phase III in the duodenum or upper jejunum. In fed pigs m.m.c.s occurred and the first phase III in the duodenum occurred within 90 min of feeding. Both portal and arterial motilin concentrations were reduced after feeding and no longer varied with the phase of the m.m.c. Altered secretion of motilin after feeding did not appear to be associated with absorption of glucose as infusion of glucose (50 g/l, 10 ml/min) into the duodenum raised arterial and portal plasma glucose concentrations to post-prandial levels yet motilin concentrations and output rates still varied with the phase of the m.m.c. Infusions of motilin (1 or 10 ng/kg X min) into the portal vein of 17 h fasted pigs did not induce an extra phase III or alter the duration of the m.m.c. Hydrochloric acid (100 mmol/l) infused into the duodenum of fasted pigs at 10-21 ml/min increased the concentration of motilin in the portal blood but was without effect at 5 ml/min. Rapid injections of 50 ml hydrochloric acid into the duodenum also increased the portal motilin concentration. Hydrochloric acid infusion or injection did not alter the interval between phase IIIs. It is concluded that motilin secretion is a consequence of the m.m.c. or shows the same periodicity as the m.m.c. but that motilin is not an important factor in the initiation and control of the m.m.c. in the pig.

Animals↗
PubMed1987

Adrenal cortical responses to vasoactive intestinal peptide in conscious hypophysectomized calves.

1. Right adrenal and various cardiovascular responses to an intra-aortic infusion of vasoactive intestinal polypeptide (VIP; 4 micrograms min-1 kg-1) have been investigated in the presence and absence of exogenous adrenocorticotrophin, (ACTH1-24; 5 ng min-1 kg-1, i.v.). The adrenal clamp technique was employed in conscious calves in which the pituitary stalk had been cauterized 3-4 days previously. 2. The i.v. infusion of ACTH1-24 increased mean plasma ACTH concentration by between 1000 and 1100 pg ml-1 and mean right cortisol output by about 700 ng min-1 kg-1. Under these conditions the intra-aortic infusion of VIP produced a further rise in mean adrenal cortisol output, together with a consequential rise in mean arterial plasma cortisol concentration, without affecting the concentration of ACTH in the arterial plasma significantly. In the absence of ACTH the same infusion of VIP had no detectable effect on adrenal cortisol output. 3. In each of the above respects this intra-aortic infusion of VIP closely mimicked the effect of stimulation of the peripheral end of the right splanchnic nerve in these animals, as it also did by causing a substantial fall in adrenal vascular resistance in the absence, but not in the presence, of ACTH. 4. It is concluded that release of this peptide from splanchnic nerve terminals in the adrenal gland most probably accounts, at least in part, for the powerful adrenocortical steroidogenic response to splanchnic nerve stimulation, that occurs in the presence of submaximal doses of ACTH.

Adrenal Cortex↗
PubMed1987

Effects of stimulating the sympathetic innervation in bursts on submandibular vascular and secretory function in cats.

1. The effects of continuous stimulation of the peripheral end of the ascending cervical sympathetic nerve were compared with those of intermittent stimulation, so arranged as to deliver the same total number of impulses, in cats under chloralose anaesthesia. 2. Continuous stimulation caused a flow of saliva at 5-10 Hz, but not at 2 Hz. In contrast, the same total number of impulses delivered intermittently in bursts elicited a prompt secretion at a frequency as low as 20 Hz for 1 s at 10 s intervals (corresponding to 2 Hz continuously) and a significantly higher rate of secretion at 50 Hz in bursts than that obtained in response to 5 Hz continuously. 3. Continuous stimulation also caused a rise in submandibular vascular resistance (s.v.r.), which persisted throughout the period of stimulation, and was followed immediately thereafter by an intense but transient fall in s.v.r. During stimulation in 1 s bursts, each burst was followed first by a brief rise in s.v.r. and shortly after by a fall. The balance between these two components varied widely between individual animals but often led to an overall fall in s.v.r. during stimulation i.e. complete reversal of the mean vascular effect. A further fall in s.v.r. was then recorded when the stimulus was discontinued. 4. Propranolol (1.0 mg/kg) reduced but failed to abolish the secretory response. It also altered the balance between the two phases of the vascular response slightly in favour of a rise in s.v.r. during stimulation, without apparently affecting the size of the after-dilatation. 5. Pre-treatment with dihydroergotamine (1.0 mg/kg) invariably blocked secretion and revealed a small vasodilator response during sympathetic stimulation with either pattern of stimulation; it also blocked the after-dilatation. 6. Following combined pre-treatment with propranolol and dihydroergotamine, to produce total adrenergic blockade, there was a small residual vasoconstrictor component which amounted to an increase in mean s.v.r. of about 20% during stimulation at 10 Hz continuously. This may have been due to release of neuropeptide Y (NPY). 7. Small but significantly greater amounts of NPY were released into the effluent blood during stimulation of the ascending cervical sympathetic nerve at 70 Hz in bursts than during continuous stimulation. No significant release of vasoactive intestinal peptide (VIP), somatostatin, bombesin, substance P or calcitonin gene-related peptide (CGRP) was observed during stimulation at any frequency.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1987

Enteroglucagon and experimental intestinal carcinogenesis in the rat.

To assess the association between the putative intestinal trophic hormone enteroglucagon and the development of intestinal tumours, four groups of 20 rats underwent either jejunal transection or 20%, 50%, or 80% proximal small bowel resection. Tumours were induced with azoxymethane 10 mg/kg weekly for 12 weeks. At 26 weeks there was a promotion of colonic neoplasia from a median of 0.5 (range 0-3) per rat in the transection group to 1.0 (0-3) in the 50% resected group (p less than 0.01) but no significant promotion in the 80% resection group. In the small bowel, increasing resection resulted in a progressive promotion of tumours from a median of 1.0 (range 0-3) per rat in the transection group to 2.0 (0-5) in the 50% resection group (p less than 0.001) and 3.0 (0-11) in the 80% group (p less than 0.01). Plasma enteroglucagon was measured at 2, 16, and 26 weeks and was raised seven-fold in the 80% resected group (p less than 0.001). There was a significant correlation between enteroglucagon concentrations and number of duodenal tumours but not colonic tumours. Crypt cell production rate in the duodenum increased from 11.5 +/- 1.9 to 29.2 +/- 1.4 cells/crypt/h in the 80% resected group (p less than 0.001) and showed a close correlation with both enteroglucagon levels and tumour promotion in the small bowel. There were no changes in crypt cell production rate in the colon with resection. This study shows a close association between enteroglucagon concentrations, promotion of tumours and crypt cell production rate in the duodenum but not in the colon.

Animals↗
PubMed1987

Delayed mouth-caecum transit of a lactulose labelled liquid test meal in patients with steatorrhoea caused by partially treated coeliac disease.

Mouth-caecum transit time (M-CTT) of a lactulose labelled liquid test meal has been measured in 27 coeliac patients and 10 healthy controls using the breath hydrogen technique. Although all patients were urged to maintain a gluten free diet, not all did, and there was, therefore, a wide range in the severity of fat malabsorption within the patient group. Gastric emptying of a 113Indium DTPA-labelled liquid test meal was also assessed in separate studies on six healthy controls and 11 of the coeliac patients. Fasting breath hydrogen concentrations and the response to lactulose, as assessed both by the rate of rise, and the peak breath hydrogen concentration reached, showed no difference between coeliacs and controls, regardless of the presence or absence of steatorrhoea. Mouth-caecum transit time in the 16 coeliac patients with steatorrhea (faecal fat greater than 7 g/24 h) was, however, significantly prolonged being 158 +/- 18 minutes (mean +/- SEM), compared with 70 +/- 9 minutes for the controls (p less than 0.02), and 83 +/- 15 minutes for the 11 coeliacs without steatorrhoea (p less than 0.002). Mouth-caecum transit time in the coeliac patients was linearly related to the 24 hour faecal fat excretion, r = 0.55, n = 27, p less than 0.01. Slow mouth-caecum transit in the coeliacs with steatorrhoea was not caused by delayed gastric emptying as the t1/2 for coeliacs with steatorrhoea was within the normal range. Coeliacs with delayed mouth-caecum transit had impaired insulin release but the postprandial profiles of the other peptides measured (cholecystokinin, GIP, secretin, motilin, neurotensin, enteroglucagon, and peptide YY) were all within the normal range in this group of partially treated coeliac patients.

Adult↗
PubMed1987

Effects of peptide YY (PYY) on mouth to caecum intestinal transit time and on the rate of gastric emptying in healthy volunteers.

The effect of an infusion of two doses of peptide YY (PYY), a novel putative gastrointestinal hormone, has been assessed on mouth to caecum intestinal transit time and on the rate of gastric emptying after ingestion of an inert 200 ml liquid meal thought unlikely to interrupt fasting gastrointestinal motility patterns. A low dose of PYY was chosen to give plasma concentrations within the range seen postprandially in healthy subjects, while the high dose mimicked the raised levels seen in several malabsorptive conditions. During infusion of PYY at 0.18 pmol/kg/min plasma concentrations rose from a basal of 8 +/- 2 pmol/l to 38 +/- 5 pmol/l and at 0.51 pmol/kg/min to 87 +/- 10 pmol/l. Mouth to caecum transit time was delayed from 67 +/- 4 mins on the saline infusion day to 94 +/- 7 mins (p less than 0.01) on the low dose and 192 +/- 9 mins (p less than 0.001) on the high dose infusion day. Time to 50% gastric emptying was prolonged from 37 +/- 8 mins during saline infusion to 63 +/- 10 mins (p less than 0.05) during low and 130 +/- 12 mins (p less than 0.001) during high dose infusion. Thus the infusion of PYY shows a dose related inhibition of mouth to caecum intestinal transit time and of the rate of gastric emptying and suggests this novel hormonal peptide to be of importance in gastrointestinal physiology.

Dose-Response Relationship, Drug↗
PubMed1987

Effects of an elemental diet, inert bulk and different types of dietary fibre on the response of the intestinal epithelium to refeeding in the rat and relationship to plasma gastrin, enteroglucagon, and PYY concentrations.

Refeeding starved rats with an elemental diet resulted in a marked increase in crypt cell production rate (CCPR) in the proximal small intestine but not in the distal regions of the gut. Little effect on CCPR was noted when inert bulk (kaolin) was added to the elemental diet. Addition of a poorly fermentable dietary fibre (purified wood cellulose) had little effect on intestinal epithelial cell proliferation except in the distal colon where it significantly increased CCPR. A more readily fermentable fibre (purified wheat bran) caused a large proliferative response in the proximal, mid, and distal colon and in the distal small intestine. A gel forming fibre only significantly stimulated proliferation in the distal colon; the rats in this group, however, did not eat all the food given. There was no significant correlation between CCPR and plasma gastrin concentrations, but plasma enteroglucagon concentrations were significantly correlated with CCPR in almost all the sites studied. Plasma PYY concentrations also showed some correlation with CCPR, especially in the colon. Thus while inert bulk cannot stimulate colonic epithelial cell proliferation fermentable fibre is capable of stimulating proliferation in the colon, and especially in the distal colon: it can also stimulate proliferation in the distal small intestine and it is likely that plasma enteroglucagon may have a role to play in this process.

Animals↗
PubMed1987

Proliferative effects of 'fibre' on the intestinal epithelium: relationship to gastrin, enteroglucagon and PYY.

Refeeding starved rats with a fibre free 'elemental' diet increased crypt cell production rate (CCPR) in the proximal small intestine but not in the distal regions of the gut. Little effect on CCPR was seen when inert bulk (kaolin) was added to the 'elemental' diet. Addition of a poorly fermentable dietary 'fibre' (purified wood cellulose) had little effect on intestinal epithelial cell proliferation except in the distal colon where it significantly increased CCPR. A more readily fermentable 'fibre' (purified wheat bran) caused a large proliferative response in the proximal, mid and distal colon and in the distal small intestine. A gel forming 'fibre' also stimulated proliferation in the distal colon. There was no significant correlation between CCPR and plasma gastrin concentrations, but plasma enteroglucagon concentrations were significantly correlated with CCPR in almost all the sites studied. Plasma PYY concentrations also showed some correlation with CCPR, especially in the colon. Thus, whilst inert bulk cannot stimulate colonic epithelial cell proliferation, fermentable 'fibre' is capable of stimulating proliferation in the colon, and especially in the distal colon: it can also stimulate proliferation in the distal small intestine and it is likely that plasma enteroglucagon may have a role to play in this process.

Animals↗
PubMed1987

Gut hormones in adaptation.

The presence of a circulating factor affecting gut growth can be surmised from the findings in gut isolated from the main food stream and not under direct nutritional influence. Thus when a Thiry Vella fistula is constructed and the crypt cell production rate counted in the fistula it can be shown to correlate with the degree of resection of the main bowel left in continuity. The only hormones which become raised in a similar pattern are enteroglucagon and peptide tyrosine tyrosine (PYY). Enteroglucagon has been shown to be part of preproglucagon, which contains in addition oxyntomodulin, glucagon like peptide 1 1-37 and 6-36NH2 and glucagon like peptide 2. These form the main candidates for the 'hormone of gut growth'. Peptide tyrosine tyrosine has been tested by direct administration over 12 days, matching the natural rise, but no affect on crypt cell production rate was seen. Glucagon like peptide 1 1-37 was similarly tested and also found to produce no effect. It remains to test the other members of the glucagon family to confirm or refute the hypothesis that one of them is the enigmatic small gut growth factor.

Adaptation, Physiological↗
PubMed1987

Some aspects of neuroendocrine pathology.

The advent of modern microscopical investigative methods for the determination of neuroendocrine differentiation has increasingly given credence to the original concept of a "diffuse endocrine system". These methods include a variety of silver impregnation techniques, technologically advanced light and electron microscopical immunocytochemistry, and, lately, the ability to localise specific binding sites by in vitro autoradiography and mRNA species by in situ hybridisation. Further insight has been gained into the possible role of regulatory peptides contained in the so called "diffuse endocrine system" and into the nature of disease processes by investigating the role of the system in benign and malignant disease.

Animals↗
PubMed1987

Co-secretion of calcitonin gene-related peptide, gastrin-releasing peptide and ACTH by a carcinoid tumour metastasizing to the cerebellum.

A carcinoid tumour presenting as Cushing's syndrome is reported. Although no tumour mass could be initially identified the patient returned with first a liver and subsequently a cerebellar mass both of which were resected. Only at post-mortem was the lung primary discovered. ACTH, gastrin-releasing peptide (GRP) and calcitonin gene-related peptide were elevated in plasma before resection of the hepatic tumour. These peptides were demonstrated in both the hepatic and cerebellar tumours by immunocytochemistry and radioimmunoassay. This case illustrates the occasional tendency of primary lung carcinoids to remain small and clinically undetectable while generating secondary tumours which are symptomatic. It is suggested that immunological demonstration of GRP may be diagnostically helpful in directing attention to the lung as a primary site in neuroendocrine tumours which present in this fashion.

Adrenocorticotropic Hormone↗
PubMed1987

Regulatory peptides in the respiratory tract of Macaca fascicularis.

The quantitative distribution and localisation of seven regulatory peptides (vasoactive intestinal peptide (VIP), peptide histidine methionine (PHM), calcitonin gene related peptide (CGRP), galanin, substance P, neuropeptide tyrosine (Y), and bombesin like peptides) were determined by radioimmunoassay and immunocytochemistry in six different regions of the respiratory tract of the cynomolgus monkey, Macaca fascicularis. In general, peptide concentrations were higher in the airways than in lung tissue itself. VIP and PHM were found in greatest abundance and in equimolar concentrations. Concentrations of substance P, neuropeptide Y, and bombesin were substantially lower. Immunocytochemistry localised all the peptides to nerve fibres, whose density generally paralleled the tissue concentrations by radioimmunoassay except in the case of bombesin, which was not detected. VIP, PHM, and galanin were mostly associated with glands of trachea and bronchus and with blood vessels and smooth muscle; CGRP and substance P were found principally beneath airway epithelium and around smooth muscle fibres and blood vessels; neuropeptide Y was found around blood vessels and seromucous glands only. The pattern of peptide distribution in the Macaca fascicularis respiratory tract is similar to that previously reported in human postmortem material, suggesting that the cynomolgus monkey may be a useful model for examining the pathophysiological role of peptides in human respiratory disease.

Animals↗
PubMed1987

Effect of substance P on cardiovascular and respiratory function in subjects.

The effect of substance P (SP), administered both intravenously and by inhalation, has been studied in normal and asthmatic humans. Intravenous infusion of SP (0.2-3.3 pmol X kg-1 X min-1) achieving a plasma concentration of SP between 5 and 25 pM produced vasodilatation (mean +/- SD), maximal increase in skin temperature (0.9 +/- 0.3 degree C) (P less than 0.05), and fall in diastolic blood pressure (8.5 +/- 2.9 mmHg) (P less than 0.05) associated with an increase in heart rate (15 +/- 10 beats/min) (P less than 0.05). All subjects had a fall in Vp30 (airflow at 70% of forced vital capacity measured from total lung capacity after a forced partial expiratory flow maneuver) at low infusion rate (P less than 0.05) and a significant rise at the highest infusion rate (P less than 0.05). Ventilation at rest and when stimulated by transient hypoxia increased (mean increase in resting ventilation 0.73 +/- 0.4 l/min and mean percent increase in transient ventilatory hypoxic response 41 +/- 27%). There was a small nonsignificant increase in plasma norepinephrine but no change in epinephrine or histamine. Inhaled SP, up to 0.7 mumol, caused a small nonsignificant fall in airway function in asthmatic subjects. SP has demonstrable effects on vascular smooth muscle and control of ventilation but at the doses studied had little effect on airway function.

Adult↗
PubMed1987

Effect of a long-acting somatostatin analogue (SMS 201-995) on postprandial gastric emptying of 99mTc-tin colloid and mouth-to-caecum transit time in man.

The effect on gut motility of a single subcutaneous injection of 50 micrograms of the long-acting somatostatin analogue, SMS 201-995, was investigated in 8 normal volunteers who took a drink containing 99mTc and lactulose with a mixed meal. The rate of gastric emptying was assessed by disappearance of the isotope from the stomach area as measured by a gamma camera, and mouth-to-caecum transit time (MCTT) was measured by the appearance of hydrogen in the breath. Gastric emptying was accelerated, with a significant reduction of the time taken to 50% isotope disappearance (37.2 +/- 3.3 min during control study vs 23.3 +/- 3.4 min after SMS injection; p less than 0.01). In contrast, MCTT was prolonged from 57.3 +/- 9.4 min (control) to 203.6 +/- 14.7 min after SMS (p less than 0.001).

Adult↗
PubMed1987

Regulatory peptide distribution in separated layers of the human jejunum.

The distribution of regulatory peptides was studied in the separated epithelium, lamina propria, submucosa and muscularis externa of the human jejunum. Gastrin, secretin, gastric inhibitory polypeptide, enteroglucagon and neurotensin immunoreactivity were almost confined to the endocrine cell-containing mucosal epithelium (greater than 98% of the total content), only minor amounts of motilin being detected in non-epithelial layers (3.6 +/- 0.7%, mean +/- SEM, n = 7). Conversely, vasoactive intestinal polypeptide, substance P and mammalian bombesin were virtually limited to non-epithelial layers (greater than 99%). Only somatostatin was found in all layers (44 +/- 6.7% in the epithelium, 34 +/- 5.2% in the lamina propria, 13 +/- 2.9% in the submucosa, and 7.9 +/- 2.8% in the muscularis). Substance P was found in higher concentrations in the mucosa, compared to submucosa and muscle (56 +/- 10, 30 +/- 4.0 and 29 +/- 4.0 pmol/g, respectively), while vasoactive intestinal polypeptide was more abundant in the muscle (411 +/- 52 pmol/g) compared to mucosa and submucosa (228 +/- 64 and 219 +/- 31 pmol/g, respectively). Only low levels of mammalian bombesin were measured, mainly in the muscle (6.9 +/- 1.5 pmol/g, or 89 +/- 3.6% of total content).

Aged↗