Development of a radioimmunoassay to a fragment of vasostatin II.
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Amino Acid Sequence↗
Biomedical subjects
K D Buchanan
Publications and source records attributed to K D Buchanan.
Serum neurone-specific enolase as an indicator of stroke volume.
Serum neurone-specific enolase (NSE) and computerized tomography (CT) stroke volume were compared in patients admitted within 24 h of an acute stroke. Serum samples were obtained on admission and daily for the next 4 days. Of 163 patients, CT scans revealed 25 with intracerebral haemorrhages, one haemorrhagic infarct and 83 measurable acute infarcts. The serum NSE levels of those with infarcts was significantly higher than in those with haemorrhages at 48 (P = 0.0003) and 72 h (P = 0.04). The maximum serum NSE value tended to occur later in those with large infarcts (P = 0.0035). There was a significant correlation between infarct volume and serum NSE at 48 h (r = 0.27, P = 0.015) and 96 h (r = 0.27, P = 0.015) and with the maximum serum NSE over the 4 days (r = 0.36, P = 0.001). There was no significant correlation between haemorrhage volume and NSE. In conclusion, serum NSE may be a useful marker of infarct volume in studies of therapy in acute stroke. Sampling for NSE should continue, at least in those with large infarcts, for longer than 4 days. Serum NSE cannot be used to distinguish between haemorrhage and infarction in patients with an acute stroke.
Adult↗
Adrenomedullin: a novel cardiovascular regulatory peptide.
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Adrenomedullin↗
Clinical studies of multiple endocrine neoplasia type 1 (MEN1)
Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder characterized by the combined occurrence of parathyroid, pancreatic islet and anterior pituitary tumours. To facilitate a screening programme for MEN1, we investigated 709 people (364 males and 345 females, age range 1-84 years) from 62 MEN1 families, and 36 non-familial MEN1 patients. Of those investigated, 220 (95 males and 125 females, age range 8-79 years) suffered from MEN1. Parathyroid, pancreatic and pituitary tumours occurred in 95%, 41% and 30% of the patients, respectively. Parathyroid tumours were the first manifestation of MEN1 in 87% of patients, and amongst the pituitary and pancreatic tumours, somatotrophinomas and gastrinomas were more common in patients above the age of 40 years, whilst insulinomas occurred more frequently in patients below the age of 40 years. Biochemical screening indicated that the penetrance of MEN1 by the ages of 20, 35 and 50 years was 43%, 85% and 94%, respectively, and that the development of MEN1 was confined to first-degree relatives in 91% of patients and to second-degree relatives in 9% of patients. These findings have helped to define a proposed screening programme for MEN1.
Adolescent↗
Expression of bcl-2 oncoprotein in pituitary tumours: comparison with c-myc.
AIMS/BACKGROUND: Whereas the control of hormone secretion from pituitary adenomas has been studied in considerable detail, the molecular events underlying the development of these tumours are still poorly understood. Abnormalities of some oncogenes and tumour suppressor genes have been previously reported to occur at very low frequencies. The aim of the present study was to assess the possible expression of the bcl-2 oncoprotein and to compare it with that of c-myc in pituitary adenomas. METHODS: Monoclonal antibodies were used, along with microwave antigen retrieval and the avidin-biotin immunohistochemical method, to investigate expression of the oncoproteins bcl-2 and c-myc in 30 primary pituitary tumours from five broad diagnostic groups and in five normal pituitaries. RESULTS: Bcl-2 and c-myc immunoreactivities were detected in nine (30%) and eight (27%) tumour samples, respectively. Of the nine bcl-2 and eight c-myc positive tumours, seven were positive for both oncoproteins and included one of the four corticotrophinomas studied, four of seven prolactinomas, one of two somatotrophinomas, and one of four oncocytomas. All 13 null cell adenomas studied were negative for both bcl-2 and c-myc immunoreactivities. CONCLUSIONS: These results indicate that the bcl-2 and c-myc oncoproteins are expressed abnormally in over one quarter of pituitary tumours. Most these tumours co-expressed both oncoproteins. The genetic complementation of simultaneously deregulated bcl-2 and c-myc is implicated, through the regulation of apoptosis, in the pathogenesis of pituitary tumours.
Adenoma↗
Occurrence of WE-14 and chromogranin A-derived peptides in tissues of the human and bovine gastro-entero-pancreatic system and in human neuroendocrine neoplasia.
Antisera were generated to the synthetic peptides SREWEDS and KELTAE which correspond to residues 315-321 and 332-337 of human chromogranin A (CgA) respectively. KELTAE represents the C-terminal hexapeptide of WE-14, and SREWEDS (residue 316 human CgA Lys/Arg substitution) represents the C-terminal heptapeptide of the Intervening Peptide, located between pancreastatin and WE-14. The antisera were employed to study the occurrence of WE-14 and CgA-derived peptides in human and bovine gastro-entero-pancreatic (GEP) tissues and in a range of human GEP neuroendocrine tumours. Immunocytochemical analyses of normal human and bovine tissues demonstrated that each antiserum immunostained endocrine cells throughout the GEP tract, Variable intensities of immunostaining were detected in neoplastic tissues. Quantitatively, the highest levels of SREWEDS and KELTAE immunoreactivity were detected in pancreatic extracts, with lower levels in gastrointestinal tissues. Elevated levels of each immunoreactant were detected in neoplastic tissues. Chromatographic analysis resolved several SREWEDS-related peptides and a major KELTAE-related peptide that co-eluted with synthetic human WE-14. The present study has demonstrated that CgA is processed to generate distinct peptide products in normal and neoplastic tissues of the GEP system. A single molecular species co-eluting with synthetic human WE-14 was predominant and consistently detected in all the tissues studied.
Aged↗
Normalization of insulin responses to glucose by overnight infusion of glucagon-like peptide 1 (7-36) amide in patients with NIDDM.
Glucagon-like peptide 1 (GLP-1) is a natural enteric incretin hormone, which is a potent insulin secretogogue in vitro and in vivo in humans. Its effects on overnight glucose concentrations and the specific phases of insulin response to glucose and nonglucose secretogogues in subjects with NIDDM are not known. We compared the effects of overnight intravenous infusion of GLP-1 (7-36) amide with saline infusion, on overnight plasma concentrations of glucose, insulin, and glucagon in eight subjects with NIDDM. The effects on basal (fasting) beta-cell function and insulin sensitivity were assessed using homeostasis model assessment (HOMA) and compared with seven age- and weight-matched nondiabetic control subjects. The GLP-1 infusion was continued, and the first- and second-phase insulin responses to a 2-h 13 mmol/l hyperglycemic clamp and the insulin response to a subsequent bolus of the nonglucose secretogogue, arginine, were measured. These were compared with similar measurements recorded after the overnight saline infusion and in the control subjects who were not receiving GLP-1. The effects on stimulated beta-cell function of lowering plasma glucose per se were assessed by a separate overnight infusion of soluble insulin, the rate of which was adjusted to mimic the blood glucose profile achieved with GLP-1. Infusion of GLP-1 resulted in significant lowering of overnight plasma glucose concentrations compared with saline, with mean postabsorptive glucose concentrations (2400-0800) of 5.6 +/- 0.8 and 7.8 +/- 1.4 mmol/l, respectively (P < 0.0002). Basal beta-cell function assessed by HOMA was improved from geometric mean (1 SD range), 45% beta (24-85) to 91% beta (55-151) by GLP-1 (P < 0.0004). First-phase incremental insulin response to glucose was improved by GLP-1 from 8 pmol/l (-8-33) to 116 pmol/l (12-438) (P < 0.005), second-phase insulin response to glucose from 136 pmol/l (53-352) to 1,156 pmol/l (357-3,748) (P < 0.0002), and incremental insulin response to arginine from 443 pmol/l (172-1,144) to 811 pmol/l (272-2,417) (P < 0.002). All responses on GLP-1 were not significantly different from nondiabetic control subjects. Reduction of overnight glucose by exogenous insulin did not improve any of the phases of stimulated beta-cell function. Prolonged intravenous infusion of GLP-1 thus significantly lowered overnight glucose concentrations in subjects with NIDDM and improved both basal and stimulated beta-cell function to nondiabetic levels. It may prove to be a useful agent in the reduction of hyperglycemia in NIDDM.
Blood Glucose↗
Overexpression of the tumour suppressor gene p53 is not implicated in neuroendocrine tumour carcinogenesis.
The tumorigenesis of neuroendocrine tumours remains poorly understood, although a minority, the familial multiple endocrine neoplasia (MEN 1 and MEN 2), are known to be of uncommon genetic origin. Mutation of the tumour suppressor gene, p53, is now known to be a common genetic alteration in about half of all types of non-endocrine cancers. In the present study, immunocytochemistry using the monoclonal anti-p53 antibody, DO-7, has been employed to investigate the accumulation of p53 immunoreactivity in a wide range of primary neuroendocrine tumours. Tumours (n = 109) were fixed and processed to paraffin wax according to a constant protocol. Sections were subjected to microwave antigen retrieval prior to immunostaining for p53. Positive nuclear immunostaining was observed in one medullary carcinoma of the thyroid (MCT), one lung carcinoid, and five small cell carcinomas of the lung (SCCL). All other tumour samples were consistently negative. As the neoplasia investigated in this study comprised a wide spectrum of neuroendocrine tumour types and ranged from minute, relatively benign lesions to malignant metastasizing disease and as there was no relationship between the presence of p53 overexpression and clinico-pathological features, the present study suggests that p53 gene mutation may be relatively unimportant in the genesis of neuroendocrine tumours.
Antibodies, Monoclonal↗
Pancreatic vipomas: spectrum of presentation and evolution of diagnostic and therapeutic modalities.
Two patients are reported who presented with symptoms characteristic of a pancreatic vipoma. The necessity to measure more than one plasma VIP level for diagnosis, and the delay between the onset of illness and diagnosis is illustrated by both cases. Evidence suggests that vipomas are still under reported. The evolution of sophisticated diagnostic and therapeutic modalities over the twenty-five years separating both presentations is discussed.
Combined Modality Therapy↗
Successful pregnancy in association with Zollinger-Ellison syndrome.
Persistent severe vomiting in pregnancy may be caused by underlying disease and should be investigated. A patient with intractable vomiting associated with abdominal pain and dental enamel erosion in two pregnancies had a gastrinoma. Symptoms were successfully controlled with omeprazole in a third pregnancy. All three babies were healthy.
Adult↗
Localization of Diploptera punctata allatostatin-like immunoreactivity in helminths: an immunocytochemical study.
The nervous systems of helminths are predominantly peptidergic in nature, although it is likely that the full range of regulatory peptides used by these organisms has yet to be elucidated. Attempts to identify novel helminth neuropeptides are being made using immunocytochemistry with antisera raised against peptides isolated originally from insects. One of these antisera was raised against allatostatin III, a peptide isolated originally from the cockroach, Diploptera punctata, and a member of a family of related peptides found in insects. Allatostatin immunoreactivity was found throughout the nervous systems of Mesocestoides corti tetrathyridia, and adult Moniezia expansa, Diclidophora merlangi, Fasciola hepatica, Schistosoma mansoni, Ascaris suum and Panagrellus redivivus. Immunostaining was observed in the nerve cords and anterior ganglia of all the helminths. It was also apparent in the subtegumental nerves and around the reproductive apparatus of the flatworms, in neurones in the pharynx of D. merlangi, F. hepatica, A. suum and P. redivivus, and in fibres innervating the anterior sense organs in the nematodes. Immunostaining in all species was both reproducible and specific in that it could be abolished by pre-absorption of the antiserum with allatostatins I-IV. These results suggest that molecules related to the D. punctata allatostatins are important components in the nervous systems of a number of helminth parasites, and a free-living nematode. Their distribution within the nervous system suggests they function as neurotransmitters/neuromodulators with roles in locomotion, feeding, reproduction and sensory perception.
Animals↗
Human gastrin and vasoactive intestinal polypeptide responses to endurance running in relation to training status and fluid ingested.
1. Plasma concentrations of gastrin, glucose, vasoactive intestinal polypeptide and non-esterified fatty acid were analysed in six male endurance runners and six male hockey players before, during and 15 min after 90 min treadmill running at 65% maximum oxygen uptake under two conditions: no fluid ingestion (trial A) and ingestion of 8% maltodextrin solution (trial B). 2. Exercise resulted in significantly elevated plasma gastrin concentrations compared with resting values in both groups after trial A (endurance runners, 69.4 ng/l; hockey players 71.4 ng/l) and trial B (endurance runners, 105.5 ng/l; hockey players, 83.2 ng/l). The gastrin response was not significantly different between the trials. 3. Plasma vasoactive intestinal polypeptide levels increased significantly beyond resting levels for both groups during trial A (endurance runners, 76.1 +/- 53.7 ng/l; hockey players 155.6 +/- 41.9 ng/l) and trial B (endurance runners 47.5 +/- 21.3 ng/l; hockey players 132.9 +/- 43.9 ng/l). The vasoactive intestinal polypeptide response to trial B was significantly attenuated compared with trial A. 4. There were no significant differences between endurance runners and hockey players for plasma gastrin, although hockey players produced significantly elevated concentrations of plasma vasoactive intestinal polypeptide after both trials compared with endurance runners. 5. Plasma glucose levels throughout trial B were significantly greater than after trial A irrespective of the group. Plasma glucose concentrations were not significantly different between endurance runners and hockey players. 6. Plasma non-esterified fatty acid concentrations rose significantly for both groups throughout exercise. Trial B resulted in an attenuated non-esterified fatty acid response compared with trial A.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Circulating gastrointestinal hormone changes in marathon running.
The purpose of this study was to observe the effect of marathon running on the release of gastrointestinal hormones and whether these might be related to gastrointestinal disturbances in marathon runners. Vasoactive intestinal polypeptide, gastrin, secretin, pancreatic polypeptide, neurokinin A, pancreastatin, insulin and glucagon-like peptide 1 were measured before, immediately upon finishing and 30 min after the race. Twenty-six competitors of the 1992 Belfast Marathon volunteered for this study. They had a mean age of 37 years and a mean finishing time of 239 min. Eight of the subjects complained of gastrointestinal distress during the race. The circulating concentration of all the GI hormones measured, except insulin were significantly elevated after the race. There was no significant change in glucose levels at the finish of the race. Statistical analysis revealed no direct relationship between the large increases in hormone levels and the occurrence of GI symptoms. These results show that GI hormone concentrations are affected by marathon running. Mechanisms of release and possible roles are discussed.
Adult↗
The natriuretic peptide family.
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Amino Acid Sequence↗
Expression of a novel receptor for the calcitonin peptide family and a salmon calcitonin-like peptide in the alpha-thyrotropin thyrotroph cell line.
We have previously shown an increased incidence of alpha-subunit-producing thyrotroph tumors after salmon calcitonin (sCT) injection into rats. However, it is not clear whether the effects of CT are direct or indirect. Our hypothesis was that for sCT to act directly, it must have a binding site on thyrotrophs. The alpha TSH cell line was used as a model for thyrotrophs. Receptor binding studies using alpha TSH membranes revealed a high affinity binding site for sCT [IC50 = 0.97 +/- 0.18 nM (n = 4); Kd = 5.45 +/- 0.43 nM (n = 3); binding capacity = 6.6 pmol/mg protein (n = 3)]. Rat CT did not compete with binding at this site. Receptor screening for other CT peptide family members revealed high specific binding for CT gene-related peptide (CGRP; IC50 = 0.25 +/- 0.08 nM; n = 3) and islet amyloid polypeptide (IC50 = 4.36 +/- 1.1 nM; n = 3). This together with the absence of rat CT binding excluded a conventional CT-binding site, and we propose a site similar to the CGRP subtype III receptor described in the rat nucleus accumbens. Guanosine 5'O-(3-thiotriphosphate) (GTP gamma S) (20 microM), reduced [125I]CGRP binding to 38% of maximal, indicating that this site is G-protein coupled. Immunocytochemically, all of the cells displayed intense sCT-like immunoreactivity, which was totally abolished by preabsorption of the antibody with sCT. The presence of this receptor supports the hypothesis that sCT mediates tumorigenesis via a direct pituitary action and, together with the coexistence of a sCT-like peptide in these cells, provides evidence for a possible autocrine role of this peptide in the control of thyrotroph function.
Amyloid↗
Serum neurone-specific enolase concentrations in patients with neurological disorders.
A radioimmunoassay (RIA) has been developed for neurone-specific enolase (NSE) and used to measure serum levels in patients with a range of neurological disorders. Serum NSE levels were within the normal range in 21 patients with multiple sclerosis and 4 patients with Guillain-Barre syndrome. Normal serum NSE levels were also recorded in patients with motor neurone disease, anterior spinal thrombosis, multi-infarct disease, benign intracranial hypertension and peripheral neuropathy. However, two patients in coma, one as a result of encephalitis, the other due to subarachnoid haemorrhage (SAH) had elevated serum NSE. In the former, serum NSE levels appeared to predict a deterioration in clinical state, levels later returning to normal before an improvement in clinical condition. In the patient with SAH, levels were elevated on admission and remained elevated until death. Serum NSE levels may be of use in predicting outcome in patients with acute neurological disease.
Adolescent↗
Peptides related to the Diploptera punctata allatostatins in nonarthropod invertebrates: an immunocytochemical survey.
The allatostatins are a family of peptides isolated originally from the cockroach, Diploptera punctata. Related peptides have been identified in Periplaneta americana and the blowfly, Calliphora vomitoria. These peptides have been shown to be potent inhibitors of juvenile hormone synthesis in these species. A peptide inhibitor of juvenile hormone biosynthesis has also been isolated from the moth, Manduca sexta; however, this peptide has no structural homology with the D. punctata-type allatostatins. Investigations of the phylogeny of the D. punctata allatostatin peptide family have been started by examining a number of nonarthropod invertebrates for the presence of allatostatin-like molecules using immunocytochemistry with antisera directed against the conserved C-terminal region of this family. Allatostatin-like immunoreactivity (ALIR) was demonstrated in the nervous systems of Hydra oligactis (Hydrozoa), Moniezia expansa (Cestoda), Schistosoma mansoni (Trematoda), Artioposthia triangulata (Turbellaria), Ascaris suum (Nematoda), Lumbricus terrestris (Oligochaeta), Limax pseudoflavus (Gastropoda), and Eledone cirrhosa (Cephalopoda). ALIR could not be demonstrated in Ciona intestinalis (Ascidiacea). These results suggest that molecules related to the allatostatins may play an important role in nervous system function in many invertebrates as well as in insects and that they also have an ancient evolutionary lineage.
Amino Acid Sequence↗
The regional distribution of neuropeptides in human skin as assessed by radioimmunoassay and high-performance liquid chromatography.
In this study radioimmunoassay was used to determine neuropeptide levels in extracts from 17 differing anatomical regions of human skin. Marked regional variations of neuropeptide content for human skin were found and these variations are likely to reflect true physiological functions for the neuropeptides studied. In general the tachykinins, substance P (SP), neurokinin A (NKA) and calcitonin gene-related peptide (CGRP) were found in highest concentrations in regions of skin with the greatest tactile sensation. By contrast, highest concentrations of vasoactive intestinal peptide (VIP) and peptide histidine methionine (PHM) were found in axillary skin, where they probably play a part in axillary eccrine sweat production. Neurotensin was not found in any of the skin areas sampled, suggesting that it is relatively unimportant in human physiological skin control. Reverse-phase high-performance liquid chromatography (rpHPLC) was used to verify the results of radioimmunoassay. Both SP and NKA occurred in several regions in both their reduced and oxidized forms, as well as displaying molecular heterogeneity. CGRP occurred as one molecular species, this being alpha-CGRP, suggesting that this is the predominant molecular form in human skin. Likewise, both VIP and PHM displayed molecular homogeneity in the regions investigated by rpHPLC.
Adult↗