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Biomedical subjects

S R Bloom

Publications and source records attributed to S R Bloom.

At least 901 records · Page 50Linked to original sources

Joint contractures and diabetic retinopathy.

It has been suggested that joint contractures may be an early marker of microangiopathy, especially retinopathy, in diabetic patients. To investigate this possibility, the prevalence of contractures of the finger joints, as assessed by the painted hand technique, was compared in 106 diabetic patients without, and 105 with retinopathy (proliferative in 66%). There was an increased prevalence of contractures in those with diabetes (25.2%) as compared with an age-matched control of 106 subjects (7.5%, P less than 0.01). The prevalence of contractures was similar in those diabetics with and without retinopathy (29.5% v. 20.8%, P less than 0.1), and did not vary with the type of retinopathy. The contracture prevalence rate was also similar in those with a diabetes duration of 5 or more years (retinopathy 29.3%, no retinopathy, 30%) or of similar diabetic duration (retinopathy 20.8%, no retinopathy, 25%). Diabetic control, as assessed by HbA1, was similar in retinopathic patients with or without contractures. We conclude that although finger joint contractures are more prevalent in adult diabetic patients, they are not necessarily a reliable early indicator of the development of retinopathy of any specific type.

Adult↗

Pancreatic polypeptide and calcitonin secretion from a pancreatic tumour-clinical improvement after hepatic artery embolization.

We present a case in which plasma pancreatic polypeptide and calcitonin were found to be raised in association with an islet cell tumour of the pancreas and its hepatic metastases. In this patient, no specific endocrine syndrome was found. Therapeutic hepatic artery embolization improved the general health of the patient with no change in plasma pancreatic polypeptide, but a fall in calcitonin.

Adenoma, Islet Cell↗

A unique apudoma producing the glucagonoma and gastrinoma syndromes.

A patient is described who presented with a 10 year history of intermittent peptic ulcer symptoms and a 3 year history of an undiagnosed skin rash. Investigations indicated raised plasma levels of gastrin, glucagon and pancreatic polypeptide. A single tumour was localised to the pancreas and resected. The tumour had the typical histology of an apudoma, and contained cells which stained for gastrin, glucagon, pancreatic polypeptide and neurotensin.

Aged↗

Neurone-specific enolase and S-100: new markers for delineating the innervation of the respiratory tract in man and other mammals.

Lung innervation has been studied in the past by methylene blue staining and silver impregnation and more recently by histochemical methods. These techniques give only a partial picture of the total innervation. We have delineated the innervation of the lung in man and three other mammalian species by immunostaining with antibodies to two new markers of nervous tissue. These markers are neurone-specific enolase (NSE), an enzyme present in nerve cells in both the central and the peripheral nervous systems, and S-100, a protein found in glial cells. Throughout the respiratory tract NSE was localised in ganglion cells and nerve fibres in all species examined, while S-100 was found in the supporting glial cells of ganglia and in Schwann cells of peripheral nerves. The distribution of NSE immunoreactivity in serial sections was compared with that of acetylcholinesterase-containing, noradrenergic, and peptide-containing nerves. In all areas NSE was found to be a specific marker for all three types of nerves. Thus these two antibodies provide an effective histological means of examining both the neuronal and the non-neuronal components of the lung innervation and should be of value in investigating this system in lung disease.

Acetylcholinesterase↗

Comparison of effects of neurotensin and fat on pancreatic stimulation in dogs.

In six conscious dogs with esophageal, gastric, and pancreatic fistulas, the effects of intravenous infusion of neurotensin and intraduodenal instillation of sodium oleate on gastric and pancreatic secretion were determined under basal conditions and after exogenous (secretin and cholecystokinin octapeptides) or endogenous stimulants (feeding and duodenal acidification). Neurotensin given intravenously in graded doses (1.5-200 pmol . kg-1 . min-1) to fasted dogs produced a dose-dependent stimulation of pancreatic bicarbonate and protein secretion reaching, respectively, about 18 and 100% of maximal responses to secretin and cholecystokinin octapeptide (CCK). Duodenal oleate in graded doses (0.5-16 mmol/h) resulted in a similar pattern of bicarbonate and protein secretion but increased plasma neurotensin only to about 10% of that achieved with infusion of exogenous neurotensin producing an equal rate of pancreatic secretion. Neurotensin, like oleate, potentiated the action of secretin and CCK on pancreatic bicarbonate and had additive effects on protein response to these secretagogues. Both neurotensin and oleate increased pancreatic response to liver extract meal kept in the stomach at constant pH (5.5) and the response to sham feeding but decreased the response to ordinary feeding, probably due to the inhibition of gastric acid secretion and reduction of duodenal acidification. Neurotensin given intra-arterially directly to the pancreas or to isolated intestinal segment increased dose dependently the blood flow and oxygen consumption without affecting general circulation. We conclude that 1) neurotensin mimics the pancreatic secretory effects of intestinal fat, 2) neurotensin may contribute in part to fat-induced stimulation of the pancreatic secretion, and 3) the secretory effects of neurotensin are accompanied by a marked stimulation of intestinal and pancreatic circulation and metabolism.

Animals↗

Immunocytochemical evidence for the presence of gamma 1-MSH-like immunoreactivity in pituitary corticotrophs and ACTH-producing tumours.

The presence of gamma 1-MSH has been demonstrated in bovine neuro-intermediate lobe by biochemical methods, thus suggesting that this peptide is cleaved from the cryptic region of pro-opiocortin. In this study we report the localisation of gamma 1-MSH-like immunoreactivity in the adenohypophysis of man, ox, pig, dog and guinea-pig using immunocytochemical procedures at both light and electron microscope levels. Antisera recognising the C-terminal Arg-Phe-amide and the C-terminal penta-peptide-amide of gamma 1-MSH have been used throughout this study. The immunostaining was found in all endocrine cells of the pars intermedia (where present) and in scattered cells of the pars distalis identified as corticotrophs. No gamma 1-MSH immunoreactivity was detected in rat adenohypophysis. In addition, 7 ACTH-producing tumours (1 pituitary adenoma and 6 ectopic) were investigated and shown to contain gamma 1-MSH immunoreactive cells.

ACTH Syndrome, Ectopic↗

Ileal enteroglucagon cells after ileal-duodenal transposition in the rat.

The changes occurring in the ileal wall and in enteroglucagon cells were studied in a rat model of intestinal adaptation, obtained by the transposition of a segment of distal ileum into the mid-duodenum (6 rats, compared with 6 transected controls). After 40 days, the transposed ileal segment, compared to the equivalent segment in the controls, showed striking increase in weight, especially of the epithelium (1,585 +/- 127 vs. 305 +/- 42 mg, mean +/- SEM, p less than 0.0005). The calculated weight of enteroglucagon cells in the segment showed a smaller, but significant increase (1.7 +/- 0.3 vs. 0.8 +/- 0.2 micrograms, p less than 0.05). Plasma enteroglucagon was markedly raised (239 +/- 28 vs. 61 +/- 7.1 pmol/l, p less than 0.0005) and showed a greatly increased meal-stimulated response (1,521 +/- 284 vs. 83 +/- 43 pmol, p less than 0.0005), thus suggesting hyperactivity of enteroglucagon cells.

Animals↗

Effect of partial ileal bypass on the gut hormone responses to food in man.

The integrated response of the regulatory peptides of the gastrointestinal tract to a test meal was studied in six hypercholesterolaemic patients who had undergone partial ileal bypass (PIB) and compared with responses in ten age- and sex-matched controls. Plasma motilin was found to rise significantly whereas plasma pancreatic polypeptide release was impaired after PIB. Plasma cholecystokinin rose promptly in both controls and the partial ileal bypass patients, and the latter group showed marked further rises, at 60 and 120 minutes after the meal, which were significantly higher than controls. Basal and postprandial plasma gastrin, gastric inhibitory peptide, neurotensin, enteroglucagon, insulin and pancreatic glucagon were similar in the two groups.

Adult↗

Neurotensin-like immunoreactivity in a subpopulation of noradrenaline-containing cells of the cat adrenal gland.

RIA of cat adrenal tissue extracts revealed a neurotensin-like immunoreactive material concentrated within the medulla of the gland (mean +/- SEM neurotensin concentration, 15.2 +/- 3.6 pmol/g whole gland; 47.9 +/- 18.4 pmol/g microdissected medulla). This immunoreactive material was found to elute in the region of synthetic neurotensin, thus indicating a similarity to the tridecapeptide originally isolated from bovine hypothalamus. Using immunocytochemical procedures at both light and ultrastructural levels, a neurotensin-like immunoreactive material was localized to a subpopulation of noradrenaline-containing cells quite distinct from the previously described enkephalin-immunoreactive chromaffin cells. Correlative ultrastructural observations have identified three morphologically distinct types of chromaffin cells in the medulla, indicating a marked heterogeneity within the noradrenaline cell population. The finding of neurotensin-like immunoreactivity in noradrenaline-containing cells of the cat adrenal medulla provides further evidence in support of the postulated existence of heterogeneous subpopulations of noradrenaline-containing cells and suggests a possible functional interrelationship between neurotensin and catecholamine.

Adrenal Glands↗

Molecular forms of glucagon-like immunoreactivity in porcine intestine and pancreas.

Glucagon-related polypeptides in porcine pancreas and intestine were analysed by gel-permeation chromatography and RIA. Three assays were employed: a nonspecific glucagon assay (R59) of 94% cross-reactivity with glicentin; a pancreatic glucagon assay (RCS5) directed against the C-terminal region of glucagon and of less than 0.01% cross-reactivity with glicentin; and a glicentin assay (R64) of less than 0.01% cross-reactivity with glucagon. For extracts of porcine pancreas all three assays gave similar molar concentrations of immunoreactivity. In porcine intestinal extracts immunoreactivity was detected in significant amounts only by the nonspecific glucagon (R59) and the glicentin (R64) assays, again in similar molar concentrations. The immunoreactivities present in pancreas and intestine were chromatographically and immunologically separable into six main peaks, peaks I, II, III, V, and VI being present in the pancreas, and peaks I, II, and IV in the intestine. The different immunoreactivities of the peaks allowed probable identities to be assigned to their main components. Apart from peak I, which consists of void-volume material that may interfere nonspecifically with the assays, the main components of the peaks can be interpreted as glicentin (in peak II) or fragments derived from glicentin. Peak III contains the N-terminal portion of glicentin (glicentin-related pancreatic peptide), peak IV probably contains glucagon with its 8 amino-acid C-terminal extension, peak V is pancreatic glucagon and peak VI contains smaller N-terminal glicentin fragments. These findings fit with the proposition that glicentin fulfills the role of proglucagon in the pancreas, and is the major component of enteroglucagon in the intestine.

Animals↗

Molecular forms of human enteroglucagon in tissue and plasma: plasma responses to nutrient stimuli in health and in disorders of the upper gastrointestinal tract.

A means of estimating human enteroglucagon (glucagon-like immunoreactivity of intestinal origin) in tissues and plasma is described, based on the subtraction of RIA values obtained with the C-terminal-directed glucagon antiserum RCS5 from the total glucagon-like immunoreactivity determined with the N-terminal- to midmolecule-directed glucagon antiserum R59. Gel filtration on Sephadex G-50 of human plasma and extracts of normal human intestine separated the R59 immunoreactivity into three peaks: a small peak of void volume material, a major peak coeluting with porcine glicentin, and a smaller peak coeluting with pancreatic glucagon. No RCS5 immunoreactivity was detected in the human gut, except for a small amount constituting less than 2% of the total glucagon-like immunoreactivity in the ileum and rectum only. In extracts of human pancreas, the chromatographic profiles obtained with RCS5 and R59 assays differed from the intestinal patterns, but were identical to each other, giving no evidence of a significant amount of pancreatic R59 immunoreactivity that was not also reactive with RCS5. Chromatography of plasmas from healthy subjects and patients with dumping syndrome, active coeliac disease, and tropical sprue showed that only the second major peak of R59 immunoreactivity reflected the basal or postnutrient increases in the plasma enteroglucagon concentration. In patients with exaggerated enteroglucagon release, the rise was again found to be entirely due to an increase in this peak of immunoreactivity. This major molecular form of human enteroglucagon, similar in size to porcine glicentin, is, thus, the form most likely to be of physiological and pathophysiological significance.

Adult↗

Bombesin and vasoactive intestinal polypeptide in the developing lung: marked changes in acute respiratory distress syndrome.

The quantitative distribution of bombesin- and vasoactive intestinal polypeptide (VIP)-like immunoreactivities was determined by RIA and immunocytochemistry in regions of trachea, bronchus, and whole lung at various stages of human fetal development and in neonates, children, and adults. In addition, these two immunoreactivities were studied in infants that had died of the acute respiratory distress syndrome. The concentration of bombesin-like immunoreactivity in the whole respiratory tract steadily increased during gestation, reaching a plateau at birth. In the lung, the bombesin concentration remained almost unchanged during childhood, but decreased to one tenth in the adult. In neonates with the acute respiratory distress syndrome, there was a significantly lower bombesin content in all regions of the respiratory tract compared to either normal full-term infants or 24- to 28-week-old fetuses. Immunocytochemistry localized bombesin immunoreactivity within mucosal neuroendocrine cells present in the airway epithelium throughout the respiratory tract and particularly in the intrapulmonary airways. The number of cells increased throughout gestation, reflecting the pattern found by RIA, and were greatly decreased in acute respiratory distress syndrome patients. VIP concentrations were much lower than those of bombesin and did not change significantly with gestational age. In contrast to bombesin, VIP was mainly concentrated in the upper respiratory tract. In infants with the respiratory distress syndrome, the VIP content was not different from normal. These results are compatible with the possibility that bombesin-like peptides may have a role in the normal development of the human lung.

Acute Disease↗

Long-term treatment in diabetics with acarbose, a glucosidase inhibitor: efficacy, tolerability and effect on GI hormones.

12 months therapy with acarbose in 143 type I and type II patients markedly improved the metabolic control, assessed by fasting and postprandial blood glucose determination. During 5 year acarbose treatment GIP levels were decreased and enteroglucagon levels were elevated. After withdrawal of the drug for one week GIP levels increased and enteroglucagon concentrations fell. Thus, GI-hormone changes were reversible after discontinuation of acarbose. Tolerability of acarbose was good and clinical chemistry and haematology parameters showed no changes after 1-5 years acarbose therapy. Approximately 60% of the patients had intestinal symptoms which subsided again for most patients after 1-4 weeks therapy with acarbose. Body weight remained unchanged. The glucosidase inhibitor acarbose is a new effective and safe therapeutic concept in the treatment of diabetes mellitus.

Acarbose↗

Gut hormone profile and gastric emptying in the dumping syndrome. A hypothesis concerning the pathogenesis.

Insulin, enteroglucagon, neurotensin, gastric inhibitory polypeptide (GIP), and motilin have been measured in plasma during an oral glucose test in 76 patients before or after different upper gastrointestinal operations for peptic ulceration. The patients were divided into three clinical groups in accordance with their spontaneous symptoms of dumping after ordinary meals: 26 postoperative patients into a dumping group, 30 postoperative patients into a non-dumping group, and 20 preoperative patients into a reference group. The fasting values of the five hormones were similar in the operated and non-operated groups. Insulin, enteroglucagon, neurotensin, and GIP rose significantly in all patients. The increment of insulin, enteroglucagon, and neurotensin was greater in the postoperative patients with dumping symptoms than in the postoperative and preoperative patients without dumping symptoms. All the patients had a small decrement of motilin. The resulting hypothesis is that an impaired neural control of the gastric emptying is the essential aetiological factor in the dumping syndrome. The excessively rapid delivery of the meal into the jejunum is the abnormal stimulus to the exaggerated hormone release. The response of the small intestine with regard to the hormone release is considered proportionate to the given stimulus. The abrupt fall in circulating blood volume is suggested to play a role in producing the polymorphic symptoms. Neurotensin and GIP cannot be excluded from being the factors arresting the rapid gastric emptying in patients whose neural control has been impaired after gastric surgery.

Adult↗

Effect of pectin on gastric emptying and gut hormone release in the dumping syndrome.

The effect of pectin on gastric emptying, gut hormone release, and symptoms was studied in four patients with dumping syndrome and in two healthy volunteers after ingestion of a hypertonic glucose meal with and without addition of pectin. The initial fraction emptied from the stomach was reduced in the patients, whose symptoms of dumping were abolished or alleviated by pectin. This change of the emptying seems to be caused by a prolonged stomach transit, probably due to the viscous nature of the pectin meal. Pectin had no effect on the gastric emptying of the volunteers. The motor activity of the stomach was not altered by pectin in either the patients or volunteers. In the patients insulin, enteroglucagon, neurotensin, and gastric inhibitory polypeptide rose to higher levels after the glucose meal than after the glucose-pectin meal. The individual differences in the hormone release were considered secondary to the altered gastric emptying produced by pectin.

Adult↗

Gut hormones in inflammatory bowel disease.

We have studied fasting levels and the response to a standard test breakfast of blood glucose and several gut hormones in 24 patients with ulcerative colitis, in 14 patients with Crohn's disease, and in 14 healthy control subjects. Patients with ulcerative colitis had significantly elevated fasting human pancreatic polypeptide (HPP) concentrations, and both basal and postprandial levels of gastrin, gastric inhibitory polypeptide (GIP), and motilin were greater than normal. In contrast, patients with Crohn's disease had normal gastrin levels but had increased fasting and postprandial levels of GIP and motilin and, in addition, of enteroglucagon, compared with controls. These patients also had greater than normal HPP concentrations 30 min after the breakfast. Normal levels of insulin, pancreatic glucagon, neurotensin, and vasoactive intestinal polypeptide were found in both groups of patients. Much remains to be known about the pathophysiology of these two debilitating diseases, and the abnormal release of gut hormones may be of importance.

Adolescent↗

Tissue localization and relative distribution of regulatory peptides in separated layers from the human bowel.

The localization and distribution of regulatory peptides was studied in separated epithelium, lamina propria, submucosa, and external muscular layer from 16 specimens of human bowel. Immunoreactive enteroglucagon, gastric inhibitory polypeptide, and neurotensin were almost confined to the epithelial fraction (97.5 +/- 2.2%, 97.5 +/- 4.2%, and 99.3 +/- 1.1% of their respective total content, mean +/- SEM) and were only localized in endocrine cells. Vasoactive intestinal polypeptide-, substance P-, and bombesinlike peptides were virtually restricted to the nonepithelial layers (99.6 +/- 0.2%, 99.6 +/- 0.2%, and 100%) and were demonstrated exclusively in nerves. A particularly rich vasoactive intestinal polypeptide- and substance P-immunoreactive nerve supply was seen in the nonepithelial mucosa, which contained the highest concentrations of these peptides, while bombesin was mainly recovered from the external muscle (87.7 +/- 2.7%). Somatostatin, measured with an antiserum highly specific for somatostatin-14, was found throughout the wall, mainly in the epithelium (39.9 +/- 5.2%) and lamina propria (29.5 +/- 5.9%), but could be immunostained only in endocrine cells.

Aged↗

Resolution of recurrent Verner-Morrison syndrome by resection of metastatic vipoma.

The case of a woman with recurrent Verner-Morrison syndrome associated with a multicentric and metachronously metastatic pancreatic islet cell tumor is described. Her original symptoms resolved after distal pancreatectomy and splenectomy for an islet cell carcinoma of the tail of the pancreas. Recurrent symptoms were associated with a raised plasma vasoactive intestinal polypeptide (VIP) level, an islet cell tumor in the neck of the pancreas, and liver metastases. After partial pancreatectomy and resection of the liver metastases, her symptoms resolved and plasma VIP level normalized. This case emphasized the potential role of resection in the management of the Verner-Morrison syndrome associated with a recurrent, metastatic vipoma.

Adenoma, Islet Cell↗