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Biomedical subjects

K D Buchanan

Publications and source records attributed to K D Buchanan.

At least 91 records · Page 5Linked to original sources
PubMed1992

The primary structure and tissue distribution of an amphibian neuropeptide Y.

Neuropeptide Y (NPY) has been isolated and sequenced from brain extracts of the European common frog, Rana temporaria. Plasma desorption mass spectroscopy of the purified peptide indicated a molecular mass of 4243.3 Da which was in agreement with that deduced from the sequence (4243.7 Da), incorporating a C-terminal amide. The primary structure of frog NPY was established as: YPSKPDNPGEDAPAEDMAKYYSALRHYINLITRQRY-NH2. Frog NPY contains a single, highly-conservative amino acid substitution (Lys for Arg at residue 19) with respect to human NPY. NPY immunoreactivity was localised exclusively in nerves within the brain, pancreas and gastrointestinal tract and reverse-phase HPLC of extracts of these tissues resolved a single immunoreactive peptide of identical retention time in each case. The primary structure of NPY has therefore been highly-conserved over a considerable evolutionary time-span.

Amino Acid Sequence↗
PubMed1992

Immunoreactivity to two specific regions of chromogranin A in the nervous system of Ascaris suum: an immunocytochemical study.

Antisera to a highly conserved region of chromogranin A (sequence KELTAE) and to a hexapeptide (sequence KGQELE) adjacent to the putative C-terminus of pancreastatin, a peptide whose sequence is found within the chromogranin A molecule, have been used to examine the localisation of immunoreactivity (IR) to these peptides in Ascaris suum. IR to both peptides was found in the nerve rings and nerve cords. In addition, KGQELE-IR was also observed in the pharyngeal neurones and in a network of fibres on the surface of the female gonoduct. The staining was specific in that it could be abolished by preincubation of the antisera with the appropriate antigen. The two antisera appeared to be staining different subsets of neurones, suggesting that (at least) two peptides were being recognised. The wide-spread distribution of IR to both peptides throughout the nervous system of the parasite suggests that the peptides carrying the epitopes recognised by the antisera are of fundamental importance to the functioning of the parasite's nervous system.

Amino Acid Sequence↗
PubMed1992

Glucose tolerance, plasma insulin, HDL cholesterol and obesity: 12-year follow-up and development of coronary heart disease in Edinburgh men.

The insulin response to a standard oral glucose tolerance test (OGTT) and other anthropometric and biochemical risk factors for coronary heart disease (CHD) were measured in a random sample of 107 Edinburgh men, who were initially studied in 1976 when they were 40 and who were reexamined in 1988-89. Fasting glucose and glucose response to OGTT were higher in 1988-89 than in 1976. In contrast, insulin levels did not differ between the initial and follow-up study either before or after the glucose load. Body mass indices increased, except triceps skinfold. Changing patterns in both fasting and OGTT insulin or glucose levels in individuals were related to changes in bodyweight or in subscapular skinfolds. Modifications in serum total and HDL cholesterol were related to changes in fasting insulin and insulin area, respectively, but not to glucose data. Eleven men developed clinical CHD. Neither glucose nor insulin measures obtained in 1976 differed between those with and without CHD. Weight-height index and abdominal skin-folds were higher in those with CHD. HDL cholesterol was significantly lower (P less than 0.05). Abdominal skin-fold but not body mass index remained significant when adjusted for HDL cholesterol. This small study confirms the importance of central obesity and low HDL cholesterol but failed to identify insulin as a risk factor for CHD in this Scottish population.

Blood Glucose↗
PubMed1992

The primary structure of peptide Y (PY) of the spiny dogfish, Squalus acanthias: immunocytochemical localisation and isolation from the pancreas.

1. Endocrine cells within islets, exocrine parenchyma and ductal epithelium in the pancreas of the spiny dogfish, Squalus acanthias, were immunostained with an antiserum to the C-terminal region of mammalian neuropeptide Y (NPY). 2. Radioimmunoassay of pancreatic extracts with the same antiserum detected immunoreactivity in the dorsal lobe (338 pmol/g) and ventral lobe (433 pmol/g). Reverse phase HPLC analysis of both extracts resolved a single immunoreactive peptide. 3. The primary structure of the isolated peptide was established as: YPPKPENPGEDAPPEELAKYYSALRHYINLITRQRY.NH2. 4. Peptide Y (PY) from Squalus acanthias is identical in primary structure to an NPY-related peptide isolated from the pancreas of Scyliorhinus canicula and has a 31/36 residue homology with porcine NPY. The 5 substitutions are highly-conservative.

Amino Acid Sequence↗
PubMed1992

Chromatographic and immunological characterisation of neuropeptide Y-like and pancreatic polypeptide-like peptides from the nematode Ascaris suum.

1. Immunoreactivity (IR) towards neuropeptide Y (NPY) and pancreatic polypeptide (PP) has previously been demonstrated in nematodes by immunocytochemistry (ICC). 2. The PP- and NPY-IR in the nematode parasite Ascaris suum were analysed using HPLC and radioimmunoassays (RIAs) specific for either peptide. 3. Quantitative RIA data on the distribution of these IRs in the parasite disagreed with ICC data suggesting that different tissue treatments used in the two techniques lead to different antigen availability. 4. Significant quantities of PP- and NPY-IR were found in the pseudocoelomic fluid suggesting a role for this medium in the transport of peptides. 5. The parasite possessed chromatographically-distinct PP- and NPY-IRs, with each IR being composed of several distinct molecules.

Animals↗
PubMed1992

Neuropeptide F: primary structure from the tubellarian, Artioposthia triangulata.

1. A neuropeptide exhibiting vertebrate pancreatic polypeptide immunoreactivity has been isolated and sequenced from extracts of the terrestrial turbellarian, Artioposthia triangulata. 2. This neuropeptide, designated neuropeptide F, consists of 36 amino acid residues terminating in a phenylalaninamide. 3. The full primary structure was established as: KVVHLRPRSSFSSEDEYQIYLRNVSKYIQLYGRPRF.NH2. The molecular mass, deduced from this sequence, was 4433 Da. 4. This neuropeptide exhibits C-terminal homology with neuropeptide F (Moniezia expansa) and with the vertebrate neuropeptide Y/pancreatic polypeptide superfamily of which it may represent a phylogenetic precursor.

Amino Acid Sequence↗
PubMed1992

Exocrine pancreatic insufficiency in presumed healthy elderly subjects.

A pilot study on exocrine pancreatic function, using the 2-day para-aminobenzoic acid (PABA) test, was performed on 21 healthy elderly and 26 healthy young subjects. A PABA excretion index (PEI) less than 55%, indicating moderate to severe exocrine pancreatic insufficiency (EPI), was found in 19% of the elderly group (95% confidence limits 5-42%). While the mean value of the PEI was significantly lower in the elderly compared with the young group (Mann-Whitney Z = 2.8, p less than 0.01), there was no significant difference when the elderly subgroup with PEI less than 55% was excluded. There was no evidence of a generalized moderate to severe decline in pancreatic exocrine function with increasing age; a mild to moderate decline cannot be excluded.

4-Aminobenzoic Acid↗
PubMed1992

Regulatory peptides in the plasma of patients with chronic cardiac failure at rest and during exercise.

The levels of several regulatory peptides were measured in peripheral plasma samples from individuals with chronic cardiac failure (CCF) and matched controls in both the resting state and during a short period of maximal exercise. Basal levels of noradrenaline (NA; 705 +/- 114 vs 195 +/- 54 ng.l-1; mean +/- SEM; P < 0.05), plasma renin activity (PRA; 12.9 +/- 2.9 vs 2.1 +/- 0.3 ng AI ml-1.h-1; P < 0.05) and aldosterone (ALDO; 325 +/- 49 vs 87 +/- 8 ng.l-1; P < 0.05) were all raised in the patients with CCF, and increased further with exercise. Basal circulating levels of atrial natriuretic peptide (ANP) were also significantly higher in the CCF group compared to controls (136 +/- 35 vs 27 +/- 5 ng.l-1; P < 0.01), but the response to exercise was attenuated, so that at peak exercise, no significant difference was observed. Basal circulating levels of gastrin-releasing peptide (GRP) (29 +/- 4 vs 40 +/- 4 ng.l-1; P < 0.05) and secretin (13 +/- 1 vs 32 +/- 4 ng.l-1; P < 0.05) were significantly lower in the CCF group when compared to controls and there was no significant change in the levels of either peptide with exercise. Levels of neurokinin A (NKA), neuropeptide Y (NPY) and neurotensin (NT) were somewhat higher in patients, but the differences were not significant, and there were no changes during exercise. There were also no significant differences in the levels of vasoactive intestinal peptide (VIP), glucose-dependent insulinotropic polypeptide (GIP), insulin or glucagon in either experimental group both before and during exercise. We have therefore identified different circulating levels of certain regulatory peptides in patients with CCF, but the significance of these remains unclear.

Adult↗
PubMed1992

Pancreatic and pituitary hormonal responses to insulin-induced hypoglycaemia during muscarinic cholinergic blockade in man.

To investigate the role of muscarinic cholinergic mechanisms in mediating the pancreatic and pituitary hormonal responses to hypoglycaemia, six normal subjects were studied during acute insulin-induced hypoglycaemia under control conditions, and during blockade with intravenous atropine. During atropine blockade the response of pancreatic polypeptide was suppressed while the maximum response of plasma glucagon was significantly higher. The increment in plasma vasopressin was also increased significantly during cholinergic blockade. During blockade with atropine the responses of plasma prolactin was reduced, with a slight but significant reduction in the growth hormone response, and although a similar maximum response of plasma ACTH was achieved, this rise was delayed. These results implicate involvement of a cholinergic muscarinic inhibitory and stimulatory mechanisms in regulating the responses of pancreatic and pituitary hormones to hypoglycaemia.

Adrenocorticotropic Hormone↗
PubMed1992

Gastric inhibitory polypeptide (GIP) response in diabetes using a highly specific antiserum.

Gastric inhibitory polypeptide (GIP), a hormone secreted from the proximal small gut, is recognized as a major component of the enteroinsular axis. However, circulating levels of GIP in diabetes have been reported to be exaggerated, normal or decreased following glucose ingestion, which may be due to the presence of variable crossreacting immunoreactive GIP forms in the circulation. We have raised an antibody (S705) which recognizes only 5 kDa GIP. Using this antiserum we have measured circulating GIP levels in 18 healthy volunteers, and 13 Type 2 diabetic and 9 Type 1 diabetic patients following ingestion of 75 g glucose. As expected, blood glucose levels and blood insulin levels are significantly abnormal in the diabetic groups. On the other hand, circulating GIP levels at all time-points and integrated incremental GIP over 120 min were not different from the control group. However, we cannot exclude the possibility that apparently normal immunoreactive GIP levels in diabetes might conceal subtle alterations in biological activity which could play a role in the pathogenesis of the disease.

Adult↗
PubMed1991

Marsupial possum neurotensin: a unique mammalian regulatory peptide exhibiting structural homology to the avian analogue.

Neurotensin has been isolated from small intestinal extracts of an Australian marsupial, the brush-tailed possum (Trichosurus vulpecula). The primary structure was determined as: pGlu-Leu-His-Val-Asn-Lys-Ala-Arg-Arg-Val-Tyr-Ile-Leu. When compared with bovine neurotensin, marsupial possum neurotensin exhibits four amino acid substitutions. His for Tyr3, Val for Glu4 and Ala for Pro7 are identical with those found in chicken neurotensin. In addition, substitution of Pro10 with Val is unique among all neurotensins sequenced to date. Marsupial possum neurotensin is therefore of unique primary structure, displaying most sequence homology with its avian counterpart. This neurotensin may thus resemble the phylogenetic precursor present at the time of divergence of primitive mammals and birds.

Amino Acid Sequence↗
PubMed1991

Neuropeptides of the primary sensory neurones in rat skin: an ontogenic study.

Cutaneous primary sensory neurones contain a number of biologically-active peptides, including substance P (SP), neurokinin A (NKA) and calcitonin gene-related peptide (CGRP). However, little information is available on ontogenic changes in the tissue concentrations of these neuropeptides. In this study, the concentrations of these neuropeptides have been assessed in dorsal and ventral abdominal rat skin at various stages of development from foetal, early neonatal, late neonatal, weaner to adult, using sensitive and specific radioimmunoassays. In addition, the levels of peptide histidine isoleucine (PHI), a peptide found in non-sensory cutaneous nerves, were assessed to control the study. The levels of PHI and NKA immunoreactivity did not change significantly at any stage of development. However, the levels of SP and CGRP immunoreactivity were significantly elevated in the early neonate with CGRP remaining elevated in the late neonate. The levels of both SP and CGRP were not significantly different between other developmental groups. Significant elevations in cutaneous SP and CGRP concentrations in early neonatal life in the rat, at a time when the pups are blind and naked, may be related to control of cutaneous sensitivity, which during this period of development, has positive survival value for the pups.

Aging↗
PubMed1991

Pancreastatin-like immunoreactivity in human carcinoid disease.

Pancreastatin-like immunoreactivity has been demonstrated in human carcinoid tumors by immunohistochemistry and radioimmunoassay, employing antisera raised to a synthetic C-terminal fragment of porcine pancreastatin. Immunohistochemistry revealed intense immunoreactivity in all tumors. By radioimmunoassay, high concentrations of pancreastatin-like immunoreactivity were measured in carcinoid tumors arising from the fore-gut (mean +/- S.D. and range: 369 +/- 955 and 9.4-3670 pmol g-1, respectively, n = 14), mid-gut (mean +/- S.D. and range: 1354 +/- 1538 and 337-3978 pmol g-1, respectively, n = 5) and in metastases associated with mid-gut tumors (mean +/- S.D. and range: 684 +/- 739 and 31-2255 pmol g-1, respectively, n = 7), compared to corresponding normal tissues (less than 1.4 pmol g-1). Individuals with hepatic metastases and carcinoid syndrome had elevated circulating levels of pancreastatin-like immunoreactivity (mean +/- S.D. and range: 770 +/- 1249 and 42-4120 pmol l-1; n = 12), significantly above the normal, fasting range (mean +/- S.D. and range: 14.9 +/- 7.5 and 4-37.5 pmol l-1, respectively, n = 42). However, patients with non-metastatic carcinoid tumors (n = 4), who had been clinically cured after primary tumor resection, had plasma levels within the normal range. Chromatographic analysis of extracts of primary lung and ileal tumors, hepatic metastases from ileal tumors and plasma from individuals with carcinoid syndrome revealed molecular heterogeneity of pancreastatin-like immunoreactivity.

Adult↗
PubMed1991

The tissue distribution of rat chromogranin A-derived peptides: evidence for differential tissue processing from sequence specific antisera.

The distribution of chromogranin A and related peptides in rat tissues was investigated using sequence specific antisera. N- and C-terminal antisera and a presumptive C-terminal rat pancreastatin antiserum immunostained an extensive neuroendocrine cell population throughout the gastro-entero-pancreatic tract, anterior pituitary, thyroid and all adrenomedullary cells. However, mid- to C-terminal antisera immunostained a subpopulation of chromogranin A positive cells. Most notable of these was with the KELTAE antiserum (R635.1) which immunostained discrete clusters of adrenomedullary cells and antiserum A87A which immunostained a subpopulation of cells in the anterior pituitary and throughout the gastrointestinal tract. The present study has demonstrated the widespread occurrence of chromogranin A and related peptides in rat neuroendocrine tissues and provides evidence of tissue and cell specific processing.

Adrenal Medulla↗
PubMed1991

Hymenolepis diminuta: changes in the levels of certain intestinal regulatory peptides in infected C57 mice.

The levels of 10 regulatory peptides in acid-alcohol extracts of three regions of the small intestine (0-20%, 30-60%, and 70-100%, with respect to distance from the pylorus) have been monitored radioimmunometrically in sham-infected male (6-8 week old) C57 mice and mice given a 5-cysticercoid infection of the rat tapeworm Hymenolepis diminuta and autopsied 10 days postprimary infection and 5 days postsecondary infection (administered 28 days postprimary infection). The regulatory peptides examined were gastrin, gastrin-releasing peptide (GRP), glucagon (= enteroglucagon), motilin, neurotensin (NT), pancreatic polypeptide (PP), peptide histidine isoleucine (PHI), somatostatin (SRIF), substance P (SP), and vasoactive intestinal peptide (VIP). Statistical analyses revealed significant deviations from control values of five of the peptides (enteroglucagon and SP, both elevated; NT, PHI and VIP, all lowered) in intestinal tissue from infected mice; measurement of the same peptides in colonic extracts revealed no significant differences between infected and sham-infected mice. Parallel changes in peptide levels between normal infected and immunosuppressed infected mice were not evident, although elevations in the tissue levels of enteroglucagon and SP were found in infected Wistar rats (normal host). Results are discussed with respect to a peptidergic involvement in the pathology and host immune response to an intestinal tapeworm.

Animals↗
PubMed1991

The distribution of neuropeptides in the ocular tissues of several mammals: a comparative study.

1. The distribution of several neuropeptides (vasoactive intestinal peptide, substance P, somatostatin and neurotensin) was assessed in ocular tissues from the cow, sheep, rabbit and rat. 2. Vasoactive intestinal peptide was most abundant in the choroid and sclera in all species except the rat. Substance P was most abundant in the retina of cow and rat and in the iris/ciliary body of sheep and rabbit. Somatostatin and neurotensin were most abundant in the retina of all species examined. 3. Regulatory peptides thus display distinct regional distributions within the ocular tissues of a single species of mammal and, in addition, exhibit interspecific variation.

Animals↗
PubMed1991

Rat small intestinal morphology and tissue regulatory peptides: effects of high dietary fat.

Sprague-Dawley rats (3 weeks old) were fed on isoenergetic diets in which 40% of the total energy was provided as fat either in the form of butter (high saturated fat), olive oil (high monounsaturated fat) or maize oil (high polyunsaturated fat), with one group on low-fat (10% of total energy) standard diet as a control. Animals were killed after 8.4 (se 0.8) weeks by cardiac puncture. Similar pieces of jejunum and ileum were prepared for morphometric studies. Extracts of tissue from the proximal and distal segments of the whole small intestine from four animals per group were assayed using established techniques for enteroglucagon, motilin, neurotensin, somatostatin, substance P and vasoactive intestinal peptide (VIP). We found that maize oil and olive oil increased villus height: crypt depth ratio in both jejunum and ileum. Maize oil increased tissue concentrations of somatostatin (P less than 0.05) and substance P (P less than 0.005) in the proximal segment. Both maize oil and olive oil increased tissue concentrations of neurotensin and substance P (P less than 0.005) in the distal segments. These observations may explain the improvement of intestinal absorption of fluid following supplementation with polyunsaturated fat.

Animals↗