Biomedical subjects

K D Buchanan

Publications and source records attributed to K D Buchanan.

At least 127 records · Page 7Linked to original sources

PubMed1989

The role of morphometry in predicting prognosis in pancreatic islet cell tumors.

Morphometry of 31 pancreatic islet cell tumors was examined to determine the value of this technique in assessing tumor behavior. Patients were followed for a mean period of 5.1 years (range, 1 month-14 years) after diagnosis. Initially 17 localized and nine metastatic tumors were studied. Discriminant analysis was carried out on these cases and identified nuclear/cytoplasmic ratio and number of nuclei/mm2 as the significant discriminatory features. These were combined to derive a classification rule which was capable of correctly identifying localized and metastatic tumors in 92% of cases. The classification rule was applied subsequently to an additional five test cases, all of which were classified successfully. The failure of increased nuclear size and pleomorphism to correlate with malignancy in these tumors was confirmed. Tumors which metastasized had significantly greater gross diameters than localized lesions, but overlap existed. Mitotic counts were not a helpful discriminatory feature. Morphometry may be useful in improving histologic assessment of pancreatic islet cell tumor behavior.

Adenoma, Islet Cell↗

PubMed1989

Tachykinin immunoreactivity in the parasitic flatworm Diclidophora merlangi and its fish host the whiting (Merlangius merlangus): radioimmunoassay and chromatographic characterisation using region-specific substance P and neurokinin A antisera.

1. Tachykinin immunoreactivity has been quantified and chemically characterised in extracts of the monogenean parasite, Diclidophora merlangi and its fish host, Merlangius merlangus, by means of four tachykinin radioimmunoassays interfaced with gel permeation chromatography and reverse-phase HPLC. 2. Of the two tachykinins identified in parasite tissue, one was SP-like and the other was NKA-like, although neither was identical to previously identified tachykinins. 3. Three tachykinins were identified in extracts of whiting GI tract, one of which was a neuropeptide and also occurred in whiting brain. 4. The parasite and fish tachykinins had different molecular weights and elution profiles in HPLC analyses, and were therefore chemically distinct.

Amino Acid Sequence↗

PubMed1989

Effects of sham feeding and a meal on plasma gastrin and duodenal pH in normal and duodenal ulcer patients.

The roles of plasma gastrin and duodenal acidity in duodenal ulcer disease remain unclear. In this pathophysiologic study, plasma gastrin and dual gastro-duodenal pH were measured before, during, and after cephalic stimulation (modified sham feeding) and the ingestion of a meal in 16 duodenal ulcer (DU) patients and twelve healthy subjects. Gastrin levels were significantly higher in DU patients both in the fasting state (42.5 ng/l vs. 22.5 ng/l, p less than 0.001) and after the meal (130 vs. 60, p less than 0.02). Two separate patient subsets were identified: a "hypergastrinemic" (HRG) group exhibiting exaggerated gastrin responses and a "Normogastrinemic" (NOG) group comprised of patients with gastrin levels similar to those of controls. Only the HRG group exhibited a significant gastrin response to sham feeding. Both patient groups exhibited a delayed onset of duodenal acidity and delayed peak acid response after feeding indicative of delayed gastric emptying of the acid load. The HRG group exhibited a longer duodenal acid exposure and a prolonged return to premeal pH levels, suggesting a defective switch-off mechanism of acid secretion after duodenal acidification.

Adult↗

PubMed1989

Identification and characterization of multiple tachykinin immunoreactivities in bovine retina: evidence for the presence of a putative oxidative inactivation system for substance P.

Tachykinin immunoreactivity has been quantified and characterized in extracts of bovine retinae by combining radioimmunoassay, gel permeation chromatography, and reverse-phase HPLC. Using an antiserum specific for the C-terminal hexapeptide amide of substance P, levels of 3.43 +/- 0.33 ng g-1 and 12.45 +/- 0.76 ng g-1 (mean +/- SD, n = 5) were measured in extracts prepared by acidified ethanol and boiling 0.5 M acetic acid, respectively. Levels of neurokinin A immunoreactivity, assayed using an antiserum cross-reacting with neurokinin A (100%), neurokinin B (50%), neuropeptide K (85%), and substance P (less than 0.1%) were 12.46 +/- 0.47 ng g-1 and 7.20 +/- 0.37 ng g-1 in the same extracts. Gel permeation chromatography identified a single substance P immunoreactant eluting with substance P standard, whereas two neurokinin A immunoreactants were resolved eluting with neuropeptide K and neurokinin A standards. Reverse-phase HPLC analysis resolved immunoreactivity eluting with substance P, neurokinin A, neuropeptide K, and neurokinin B and their respective methionine sulphoxides. The amount of immunoreactive material co-eluting with the respective sulphoxides was higher in acidified ethanol extracts, and substance P was most susceptible to oxidative modification. Subsequent incubation of synthetic substance P with dispersed bovine retinal cells resulted in rapid conversion to three metabolites identified and isolated by reverse-phase HPLC. Each had an amino acid composition identical to that of substance P, and the major product had the same retention time as substance P sulphoxide.(ABSTRACT TRUNCATED AT 250 WORDS)

Amides↗

PubMed1989

Effects of growth hormone-releasing hormone on the secretion of islet hormones and on glucose homeostasis in lean and genetically obese-diabetic (ob/ob) mice and normal rats.

The effect of synthetic human growth hormone-releasing hormone(1-40) (hGHRH-40) on the function of the endocrine pancreas and on glucose homeostasis in lean and genetically obese-diabetic (ob/ob) mice and normal rats has been examined. The addition of 1 mumol hGHRH-40/1 to incubated islets from normal lean mice increased insulin release by 90 and 37% at 5.6 and 16.7 mmol glucose/l respectively. Lower concentrations of hGHRH-40 did not affect insulin release. hGHRH-40 (1 mumol/l) increased pancreatic polypeptide release by 50% at 5.6 mmol glucose/l. A range of concentrations of hGHRH-40 (1 nmol/l-1 mumol/l) reduced glucagon release by 42-73% at 5.6 mmol glucose/l, and by 38-70% at 16.7 mmol glucose/l. Somatostatin release was increased (eightfold) by 1 mumol hGHRH-40/1 at 5.6 mmol glucose/1, but at 1 nmol hGHRH-40/1 somatostatin release was reduced (by greater than 50%). At 16.7 mmol glucose/litre 0.01-1 mumol hGHRH-40/1 increased somatostatin release (three- to fourfold), but 1 nmol hGHRH-40/1 produced a reduction of 50%. In vivo, administration of hGHRH-40 (50 micrograms/kg body weight i.p.) to fasted lean and ob/ob mice did not alter basal plasma concentrations of glucose and insulin, or the glucose and insulin responses to a concomitant i.p. glucose challenge. Intravenous injection of hGHRH-40 (20 micrograms/kg body weight) to anaesthetized rats increased plasma concentrations of insulin in the hepatic portal vein. A lower dose of hGHRH-40 (0.2 micrograms/kg) was ineffective, and neither dose of hGHRH-40 altered plasma glucose.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1989

The frequency of gastrointestinal endocrine tumours in a well-defined population--Northern Ireland 1970-1985.

The reported incidence of gastrointestinal endocrine tumours is variable. In Northern Ireland circumstances allowing such an assessment are favourable with a central diagnostic laboratory and register established to collect data on tumours from a well-defined population of 1.5 million people. From 1970 to 1985, 368 cases were recorded of which 85 per cent were carcinoid tumours. The annual incidence of carcinoid tumours was 1.3 per 100,000 of the population and the majority occurred in the appendix (61 per cent). No patients presented with the carcinoid syndrome. The annual incidence for other tumours was 0.12 per 100,000 for insulinomas; islet cell tumours of unknown type 0.07; Zollinger-Ellison syndrome 0.05; and multiple endocrine neoplasia (MEN) 0.05. There were two cases of VIPoma, one glucagonoma, one neurotensinoma and one tumour producing ACTH. It is possible that some tumours are more uncommon than others because of difficulty in diagnosis.

Adenoma, Islet Cell↗

PubMed1988

Gastrin-releasing peptide (GRP) immunoreactivity in the rat retina: a radioimmunoassay, immunohistochemical and chromatographic study.

Using radioimmunoassay, reverse phase high pressure liquid chromatography (rp HPLC) and immunohistochemistry, we have identified gastrin releasing peptide-immunoreactivity (GRP-IR) in the rat retina. The concentration of GRP-IR in retinal extracts was 7.4 +/- 0.6 ng/g wet wt. (mean +/- S.E.M. n = 15). There was no significant difference between the levels of immunoreactivity in 12-h light and 12-h dark adapted retinae. rp HPLC analysis of retinal extracts demonstrated that two main immunoreactive components were present which corresponded in retention time to GRP10 (neuromedin C) and GRP14 (GRP14-27). A small amount of material also co-eluted with GRP27. Using immunohistochemistry, the immunoreactivity has been localised in the inner retinal layers. Immunoreactive somata were present in the proximal inner nuclear layer and in the ganglion cell layer. Fibre staining was present in laminae 2 and 4 of the inner plexiform layer. Somatal staining was increased by pretreatment of retinae with vincristine while the laminar staining was markedly reduced. These results demonstrate the existence of GRP-like peptides in the rat retina which has not previously been reported.

Animals↗

PubMed1988

Xenopsin immunoreactivity in antral G-cells may reside in the N-terminus of gastrin 17.

The nature of xenopsin immunoreactivity in mammalian antral G-cells has been reassessed. Xenopsin immunostaining was most intense in human antral G-cells, present in those of the dog and pig and not detected in guinea pig or rat tissues. Rigorous specificity controls for ionic binding of immunoglobulins to antral G-cell granules indicated that this mechanism was not responsible for xenopsin immunostaining. Preincubation of the xenopsin antiserum with xenopsin, human gastrin 1-13 and gastrin 2-17 completely abolished immunostaining at similar molar concentrations. Gastrin 34 was ineffective at much higher concentrations. These results infer that xenopsin-immunoreactivity in antral G-cells resides in the N-terminal region of gastrin 17. Examination of the primary structures of xenopsin and the N-terminal regions of some mammalian gastrins reveals a hitherto unrecognized homology.

Amino Acid Sequence↗

PubMed1988

Serum concentrations of trypsin-like immunoreactivity and pancreatic isoamylase in insulin dependent diabetic patients.

Serum trypsin-like immunoreactivity and pancreatic isoamylase were measured in 302 insulin-dependent diabetic patients (166 men) using radioimmunoassay for the former and a photocolorimetric method for the latter. There was a significant correlation between the two enzymes (r = 0.67, p less than 0.0001) with lower concentrations of both trypsin-like immunoreactivity (208.8 micrograms/L) and pancreatic isoamylase (67.5 U/L) in diabetic patients as compared to controls (p less than 0.0001). Using multiple regression analysis, a statistically significant association was only apparent between enzyme concentrations and age at onset of diabetes (r = 0.31, p less than 0.0001). The results suggest that impaired exocrine pancreatic function may occur in an appreciable proportion of diabetic patients and also that a primary insult to the exocrine pancreas occurring at the time of endocrine injury may be a contributory factor.

Adolescent↗

PubMed1988

Reassessment of enteric endocrine cell hyperplasia in celiac disease.

Celiac disease is characterized by reversible, gluten-induced, architectural abnormalities of the intestinal mucosa. Villus atrophy is compensated for by an increase in the number of proliferating cells and an increase in crypt cell production rate, resulting in increased crypt length and girth. Several authors, employing various methods of quantitation, have reported enteric endocrine cell hyperplasia in celiac disease. The present study has re-evaluated enteric endocrine cell status in this disorder by employing methods of quantitation which more accurately take account of alterations of crypt morphology than those previously used. Numbers of endocrine cells expressed as cells per unit of crypt length are not increased in the celiac biopsies when contrasted with those from controls. Indeed, numbers of cells immunoreactive for gastrin, GIP, motilin and somatostatin were reduced in the celiac mucosa. Endocrine cell hyperplasia in the celiac small bowel is not as marked as was previously thought, and may lag behind that of the enterocyte population.

Adult↗

PubMed1987

Direct stimulation of enzyme secretion from rat exocrine pancreas by neurotensin and its naturally occurring fragments.

Neurotensin stimulates amylase release from dispersed pancreatic acini at concentrations as low as 10(-15) M. The naturally occurring fragments of neurotensin (NT), NT 1-8 and NT 1-11, also stimulate amylase secretion at concentrations that occur in peripheral plasma (10(-11) M). The analogue D-Phe11 neurotensin was as potent as neurotensin itself with respect to stimulation of amylase secretion. Basal plasma neurotensin levels were approximately 10 pmol/L, a concentration that stimulates the exocrine pancreas in vitro. Increases in plasma neurotensin levels induced by infusion of neurotensin caused greater increases in secretion of pancreatic amylase than did similar changes of neurotensin concentration in vitro. These results suggest that in addition to its direct action, other factors are involved in modulation of the effects of neurotensin on pancreatic exocrine function in vivo.

Amylases↗

PubMed1987

Gastric inhibitory polypeptide, dietary-induced thermogenesis, and obesity.

Blood glucose, plasma concentrations of gastric inhibitory polypeptide, insulin, glucagon, cortisol, and thyroid hormones were measured in nonobese and obese human subjects at 30 and 22 degrees C ambient temperature (Ta). Oxygen consumption (VO2), carbon dioxide output (VCO2), and temperatures in the external auditory meatus (Tc) and on the skin surface (Tsk) were also measured. After 1 h, near naked at the chosen Ta, an oral dose of sucrose (approximately 1.5 g/kg) was given and the subjects were then monitored for a further 60 or 90 min. Following sucrose ingestion, both in the nonobese and obese, there were significant (p less than 0.001) increases in the following: glucose, gastric inhibitory polypeptide, insulin, VO2, and respiratory quotient. The effect of Ta on these responses in the nonobese was that gastric inhibitory polypeptide rose more at Ta 30 than at Ta 22 (p less than 0.05) and VO2 rose more at Ta 22 than at Ta 30 (p less than 0.05). In the obese, glucose rose more at Ta 30 than at Ta 22 (p less than 0.02), VO2 rise was less than in the nonobese at Ta 22 (p less than 0.05), and the respiratory quotient was lower than in the nonobese at both Ta 30 and 22 (p less than 0.001). Gastric inhibitory polypeptide changes with respect to Ta in the obese were inconsistent. It is concluded that responses to oral sucrose are modified by environmental temperature.

Blood Glucose↗

PubMed1986

Neuroendocrine tumors. A European view.

A center in Belfast, Northern Ireland, has established a register for tumors of the gastroenteropancreatic endocrine system. Carcinoid tumors occur most frequently. Of the non-carcinoid tumors, insulinomas, gastrinomas, and unknown types have the highest incidence, with other types being extremely rare. The potentially remediable nature of the tumors is stressed, and frequently a good quality of life can be experienced even in the presence of metastatic disease. The syndromes are probably underdiagnosed as they present with clinical features for which there are more common explanations, and appropriate diagnostic methods are therefore not used. The management of the syndromes is reviewed with particular emphasis on the treatment of patients with inoperable disease. Histamine (H2)-receptor antagonist therapy has made an impact in Zollinger-Ellison syndrome, and streptozotocin and somatostatin analogues can control tumor growth and endocrine syndromes, respectively.

Apudoma↗

PubMed1986

Effect of a single oral dose of enprostil on gastric secretion and gastrin release. Studies in healthy volunteers and patients with pernicious anemia.

In healthy human volunteers, a single oral dose of enprostil (35 micrograms) inhibited basal gastric acid output by a mean of 71 percent, pentagastrin-stimulated output by 46 percent, sham-meal-stimulated output by 48 percent, and histamine-stimulated output by 16 percent. In each case, there was a reduction in both the volume and acidity of the gastric juice. Pepsin output was unchanged. Although enprostil increased the gastric pH, it did not induce basal or post-prandial hypergastrinemia. In patients with hypergastrinemia secondary to achlorhydria, enprostil lowered the basal gastrin level and reduced or abolished the post-prandial gastrin rise in a dose-related fashion. Enprostil reduces basal and stimulated gastric acid secretion and inhibits gastrin release.

Achlorhydria↗

PubMed1986

Neuroendocrine cells within colorectal tumours induced by dimethylhydrazine. An immunocytochemical study.

Colorectal adenocarcinomas were induced in male Wistar rats, by weekly subcutaneous administration of 1,2-dimethylhydrazine, classified according to the degree of differentiation and submitted to immunocytochemistry for the peptides cholecystokinin (CCK), gastrin, gastric inhibitory polypeptide (GIP), glucagon, neurotensin, pancreatic polypeptide (PP), peptide YY (PYY), somatostatin and vasoactive intestinal polypeptide (VIP) and the biogenic monoamine 5-hydroxytryptamine. Well- or moderately well-differentiated adenocarcinomas comprised 46% of the tumour population, only 4% were poorly-differentiated adenocarcinomas, and the remaining 50% possessed a mixture of these two morphologies. Glucagon, PYY and 5-hydroxytryptamine immunoreactive cells were frequently observed within well- or moderately well-differentiated tumours and within such regions of tumours possessing a mixed morphological pattern. The tumours contained no cells immunoreactive for any of the peptides not normally located within the colorectum, nor did they contain cells immunoreactive for somatostatin and VIP, although known positive controls did stain. Poorly-differentiated tumours and portions of tumours of mixed type, were consistently negative. 5-hydroxytryptamine was the most frequently located of the three antigens, being detected in 87% of the moderately well-differentiated tumours and 32% of the tumours with mixed morphologies. 11% of moderately well-differentiated tumours possessed 5-hydroxytryptamine positive cells in such profusion that they contributed significantly to the tumour mass. The distribution of glucagon- and PYY-immunoreactive cells was similar, although they occurred with a lower frequency, presumably corresponding to their lower numbers within the normal colorectal mucosa. Additionally, these two peptide immunoreactivities were colocalized in the majority of cells, although some cells contained only one antigen.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗

PubMed1986

Correlation of cardiovascular and neuroendocrine tests of autonomic function in diabetes.

Six normal subjects and 16 insulin-dependent diabetics with varying degrees of autonomic damage each had blood sampled for norepinephrine and pancreatic polypeptide for fifteen minutes after a mixed meal and intravenous (IV) edrophonium (Tensilon). The normal subjects showed a brisk but short-lived rise in norepinephrine after edrophonium (average maximum increase 70% between 2 and 6 minutes), as did most diabetics. However, diabetics with cardiovascular reflex evidence of sympathetic damage showed no rise in norepinephrine. Pancreatic polypeptide concentrations increased up to 400% above baseline after a mixed meal in both the normal and the diabetic group with normal cardiovascular reflexes. There was no significant rise in pancreatic polypeptide either in the diabetics with parasympathetic damage alone or in those with additional sympathetic damage. These results provide further evidence for the diffuse nature of the damage in diabetic autonomic neuropathy.

Adult↗

PubMed1986

Pancreatic polypeptide immunoreactivity in medullary carcinoma of the thyroid: identification and characterisation by radioimmunoassay, immunocytochemistry and high performance liquid chromatography.

Pancreatic polypeptide immunoreactivity has been identified in primary medullary carcinoma of thyroid using radioimmunoassay and immunocytochemistry and subsequently characterised by HPLC. Two region-specific PP antisera were used in the study; one C-terminal and one non-C-terminal. These antisera demonstrate variable cross-reactivity with the molecular species of PP identified in the tumours. The immunoreactive material in the tumours corresponded to human PP and not PYY or NPY on the basis of immunoreactivity and HPLC behaviour. It was identified in all patients with familial-type disease but not in the two sporadic cases examined. We propose that estimation of the PP content of medullary carcinoma of thyroid may be a useful means of differentiating familial and sporadic types.

Adult↗

PubMed1986

Effect of guar on second-meal glucose tolerance in normal man.

Whole body glucose turnover and absorption of a 50 g glucose drink was studied in six healthy volunteers on two occasions, 4 h after a 'breakfast' of 50 g of glucose, mixed on one occasion with 20 g of guar gum. Plasma glucose concentrations were significantly reduced with guar gum compared with those obtained without guar gum (P less than 0.0001). Whole body glucose turnover studied by an intravenous primed dose constant infusion technique using D-[3-3H]glucose showed no significant difference between the two groups: 353 +/- 15 mmol with guar and 350 +/- 9 mmol without guar. Total oral glucose absorption, followed with a D-[1-14C]glucose tracer, was significantly decreased by guar treatment, being 219 +/- 3 mmol with guar and 239 +/- 5 mmol without guar (P less than 0.05). Serum insulin levels were lowered by guar treatment (P less than 0.05) while those of C-peptide, gastric inhibitory polypeptide, glucagon, cortisol and pancreatic polypeptide did not differ significantly. Blood lactate concentrations were raised in the guar treated group (P less than 0.05) whereas pyruvate, alanine, glycerol and 3-hydroxybutyrate concentrations did not differ significantly. These results support the suggestion that guar improves second-meal tolerance to glucose by decreasing absorption.

Adult↗