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Biomedical subjects

T E Adrian

Publications and source records attributed to T E Adrian.

At least 325 records · Page 18Linked to original sources
PubMed1976

Pancreatic polypeptide in insulinomas, gastrinomas, vipomas, and glucagonomas.

In 33 patients studied with endocrine neoplasms of the pancreas more than half the tumours contained pancreatic polypeptide (P.P.) producing cells, and a high radioimmunoassayable concentration of P.P. was found in the tumour extracts. Plasma was available from 28 patients, and very high circulating P.P. concentrations were found in 18. The presence of P.P. in hepatic and lymphnode metastases indicates that its production by the primary neoplasm cannot be ascribed to incidental adherence of normal P.P. cells. Measurements of plasma P.P. levels should be a new aid to diagnosis of pancreatic tumours.

Adenoma, Islet Cell↗
PubMed1976

Distribution and release of human pancreatic polypeptide.

A simple and reliable radioimmunoassay has been developed for a new gut hormone, HPP. In the primate 93% of the total PP was found in the pancreas with a small amount throughout the remaining gastrointestinal tract. HPP has been shown to be produced by a number of pancreatic apudomas and their metastases. The immunoreactive PP from these tumours and from normal pancreas was chromatographically indistinguishable from the pure peptide. The plasma PP concentration rose rapidly after a meal in normal subjects and was still raised six hours later. Fasting plasma PP levels in patients with PP cell containing pancreatic endocrine tumours were higher than even the postprandial level in normal subjects. PP measurements is thus useful in diagnosis of pancreatic endocrine tumours.

Animals↗
PubMedDate not supplied

Abundance of VIP in duodenal mucosa of coeliacs and duodenal ulcer patients.

VIP levels were determined in gastroduodenal mucosal biopsies of 8 duodenal ulcer patients, of 5 coeliac sprue patients, and of 8 volunteers without upper gastrointestinal disease. In duodenal ulcer patients, mucosal VIP concentrations were significantly elevated in the proximal duodenum (e.g., in the duodenal bulb 225 +/- 48 versus 95 +/- 17 pmol/g in controls), while in coeliac sprue VIP levels tended to be increased in the whole duodenum and upper jejunum (e.g., descending duodenum 409 +/- 161 versus 81 +/- 16, p less than 0.05). In both disease entities, the rise in mucosal VIP may be a reaction of the peptidergic nervous system to chronic mucosal irritation and a reason for enhanced fluid and electrolyte secretion in the affected areas.

Adult↗
PubMedDate not supplied

Measurement of cholecystokinin octapeptide using a new specific radioimmunoassay.

A peptide analogue of CCK-8 (Tyroc) which has a tyrosine in place of the amide group in the C-terminal end, has been used both for raising antisera and for iodination. The antisera produced by immunisation with Tyroc are directed towards the N-terminal end of the CCK-8 molecule. The assay system appears totally specific for the CCK-8 sulphated molecule and shows no significant cross-reaction with other molecular forms of CCK, or with the gastrins. The assay can detect changes between adjacent tubes of 0.25 fmol/tube CCK-8 with 95% confidence. The assay is robust, reliable and reproducible and can be used to measure tissue and plasma levels of CCK-8.

Animals↗
PubMedDate not supplied

Oxidation/reduction of methionine residues in CCK: a study by radioimmunoassay and isocratic reverse phase high pressure liquid chromatography.

The study was undertaken to investigate the oxidation and reduction of cholecystokinin (CCK) both as pure standards and as endogenous porcine peptides. Furthermore an attempt was made to prevent oxidation of the endogenous porcine peptides in the extraction procedure. CCK-8 and CCK-33 standards were always oxidized in weak solutions, CCK-8 varying from 26% to 67% oxidized and CCK-33 from 18% to 70%. Similarly, tissue extracts of porcine brain and duodenum contained oxidized forms of the peptide. CCK standards were readily oxidized in the presence of hydrogen peroxide. Oxidized CCK-8 standard and CCK-8 in porcine brain was 90% reduced and oxidized CCK-33 standard and in duodenal extracts was reduced by 70% by a 40 hour incubation with 0.725 mol/l dithiothreitol at 37 degrees C. Extraction of CCK peptides in the presence of 65 mmol/l dithiothreitol resulted in almost complete prevention of oxidation with over 95% of the peptides being obtained in the reduced state. This additive is therefore recommended for all tissue quantitation studies.

Animals↗
PubMedDate not supplied

Intraislet somatostatin inhibits insulin (via a subtype-2 somatostatin receptor) but not islet amyloid polypeptide secretion in the isolated perfused human pancreas.

It is our hypothesis that intraislet somatostatin regulates beta cell secretion in the isolated perfused human pancreas. The present study was designed to determine the relative influence of intraislet somatostatin on the regulation of islet amyloid polypeptide (IAPP) and insulin secretion, and to determine the effect of specific somatostatin receptor (SSTR) agonists on beta cell secretion during immunoneutralization of endogenous somatostatin in the isolated perfused human pancreas. Single-pass perfusion was performed in pancreata obtained from seven cadaveric organ donors using a modified Krebs medium with 3.9 mmol/L glucose. Sequential test periods were separated by basal periods and experiments were performed by infusion of any of the following: (1) somatostatin monoclonal antibody (S-Ab); (2) S-Ab + SSTR2 agonist (DC32-87); or (3) S-Ab + SSTR5 agonist (DC32-92). The changes in insulin and IAPP secretion from basal levels during each stimulation were calculated. Infusion of S-Ab resulted in a significant increase in insulin secretion (2033 +/- 429 pmol/L; P <0.05) but not IAPP. In the presence of S-Ab, infusion of the SSTR2 agonist resulted in a significant inhibition of insulin secretion (-1128 +/- 457 pmol/L; P <0.05) but not IAPP. In the presence of S-Ab, infusion of the SSTR5 agonist had no significant effect on insulin or IAPP secretion. We conclude that intraislet somatostatin inhibits insulin secretion via SSTR2, but not IAPP secretion, in the isolated perfused human pancreas model and that this effect occurs via SSTR2. These results also suggest that insulin and IAPP secretion are regulated by different mechanisms despite being co-localized to the beta cell.

Adolescent↗
PubMedDate not supplied

Role of the ileocecal junction in the motor response to intestinal resection.

Extensive resections of the distal small intestine are associated with motor disruption in the proximal remnant. Luminal contents such as bacteria and short-chain fatty acids may play a role. We evaluated the effect of bypass of the ileocecal junction (ICJ) on the motor response to a 50% distal resection. Thirty-five dogs were divided into three groups: transection control (TC, n = 11); 50% distal resection with intact ICJ (DR, n = 12), and 50% distal resection with jejunocolostomy to bypass the ICJ (DRBP, n = 12). Motor activity, intestinal transit, nutrition, absorption, and motor active hormones were studied over a 3-month period. Caloric intake was reduced and nutritional status similarly impaired in both resected groups. Steatorrhea, however, was significantly greater after DRBP. Intestinal structural adaptation was similar in both resected groups at 12 weeks. Animals in the bypass group demonstrated elevated intraluminal short-chain fatty acid and anaerobic bacterial counts. Migrating motor complex frequency was similar in the three groups; distal starts, however, were more frequent in both resected groups. Clustered contractile activity was prominent in the remnant after both DR and DRBP (50% and 32% recording time occupied by clusters, respectively [not significant]). Basal levels of peptide YY were increased following resection and this increase was unaffected by ICJ bypass. Postprandial neurotensin concentrations were transiently increased after distal bowel resection. In contrast, the postprandial neurotensin response was abolished following resection with bypass of the ICJ. Basal motilin levels were reduced following resection alone but not after resection with ICJ bypass. The motor response to resection does not appear to be related to alterations in circulating levels of hormones localized to the distal ileum; neither does it seem to be influenced by luminal bacteria and short-chain fatty acids or retention of a sphincteric mechanism at the ICJ. These findings also raise questions about the role of short-chain fatty acids and bacteria in the generation of the various distinctive motor patterns of the distal ileum. Resection of the distal ileum through loss of the receptor site for either retarding reflexes or bile salt absorption may be of greater importance in determining the motor response to resection.

Anastomosis, Surgical↗
PubMedDate not supplied

Effect of duodenal components of the refluxate on development of esophageal neoplasia in rats.

When duodenal content is allowed to reflux into the esophagus of nitrosamine-treated rats, esophageal cancer is induced more rapidly and at higher frequency than after carcinogen treatment alone. The purpose of the present study was to identify the components of the duodenal content that are responsible for enhancing esophageal carcinogenesis. Eight-week-old Sprague-Dawley rats underwent one of four operations as follows: diversion of bile alone, pancreatic juice alone, both bile and pancreatic juice into the esophagus, or a control operation with no induced reflux. Two weeks after surgery, rats were treated with the esophageal carcinogen 2, 6-dimethylnitrosomorpholine (48 mg/kg [0.1 of LD50] intraperitoneally weekly for 20 weeks). The rats were killed at age 30 weeks. The esophagus was removed and full-length strips were examined under a microscope; separate segments were taken for flow cytometric evaluation. The prevalence of DNA aneuploidy and histologic esophageal papillomas or squamous cancer was increased in carcinogen-treated rats with pancreatic juice reflux (P <0.05 vs. control) and the combination of pancreatic and bile reflux (P <0.05 vs. control) but not in rats with bile reflux alone. We conclude that pancreatic juice is the most potent component of the duodenal refluxate in the promotion of esophageal carcinogenesis in rats.

Aneuploidy↗
PubMedDate not supplied

Neuropeptide Y distribution in human brain.

Tatemoto and Mutt recently used the presence of a C-terminal NH2 group to identify and isolate a new peptide, neuropeptide Y (NPY), from porcine brain. This 36 amino acid peptide was subsequently shown to be active on isolated vas deferens, vascular smooth muscle and pancreatic acinar cells in very low molar concentrations. In view of these potent effects we have now investigated its distribution in the human brain by radioimmunoassay and immunocytochemistry. High concentrations of NPY have been found, exceeding those of cholecystokinin and somatostatin, hitherto considered to be the most abundant neuropeptides. The distribution of NPY was different from that of any other peptide system described, being particularly concentrated in the basal ganglia, amygdala and nucleus accumbens. Immunocytochemistry demonstrated a large number of NPY neuronal cell bodies especially in the caudate and putamen. Immunoreactive neuronal cell bodies were also clearly localized in cortical areas, particularly layers V and VI. NPY, a newly discovered peptide with potent biological activity, thus seems to be among the most abundant of human neuropeptides. The massive numbers of NPY neurones in the basal ganglia suggest NPY to be of fundamental importance in the control of human motor function.

Brain Chemistry↗
PubMedDate not supplied

Effects of feeding regimen on blood glucose levels and plasma concentrations of pancreatic hormones and gut regulatory peptides at 9 months of age: comparison between infants fed with milk formula and infants exclusively breast-fed from birth.

Little is known about the development of gut endocrine responses to food intake in infants after the first postnatal month. To examine this question and to ascertain whether the mode of feeding from birth affects postprandial endocrine changes, blood glucose levels and the plasma concentrations of 11 regulatory peptides were measured at 9 months of age before and after a breast feeding in 13 exclusively breast-fed infants and before and after a formula feeding in 7 infants weaned during the first 3 months of life. In the prefeeding concentrations of these substances, no significant differences were found between the two groups, with the possible exception of the plasma concentration of pancreatic polypeptide (p = 0.06). Postprandially, the responses were significantly smaller in the breast-fed infants, whose plasma concentrations of insulin, gastric inhibitory polypeptide, pancreatic polypeptide, and cholecystokinin were lower than in the formula-fed infants. In addition, the overall level of the insulin-glucagon ratio was lower (p = 0.03) in the breast-fed infants. A difference in the opposite direction was observed for plasma gastrin levels. No significant differences appeared between the groups for blood glucose, or plasma glucagon, vasoactive intestinal polypeptide, motilin, enteroglucagon, secretin, or neurotensin concentrations after feeding. It is concluded that at 9 months of age, the gut regulatory responses to milk feeding are of lower magnitude than during the neonatal period, but even at this age the response patterns still depend on the mode of feeding.

Animals↗
PubMedDate not supplied

Guar sprinkled on food: effect on glycaemic control, plasma lipids and gut hormones in non-insulin dependent diabetic patients.

The effects of guar granules sprinkled over food on carbohydrate and lipid metabolism were studied in a double-blind cross-over trial in 18 patients with non-insulin-dependent diabetes mellitus (mean +/- SEM age 61.3 +/- 2.5 years). Five-gram guar granules (Guarem, Rybar Laboratories, Amersham, Bucks) were sprinkled over food at each main meal for 4 weeks, and during a 4-week placebo period (separated by a 2-week 'wash-out' period), 5 g wheat bran was taken in the same way. Diabetic treatment was not changed during the study. Mean fasting plasma glucose (FPG) concentration and glycosylated haemoglobin (HbA1) concentration after treatment were significantly lower than after the placebo period (FPG 8.29 +/- 0.47 vs 8.78 +/- 0.53 mmol/l, p less than 0.05; HbA1: 8.70 +/- 0.39 vs 9.09 +/- 0.39%, p less than 0.05). There was a 50% reduction in the incremental area under the postprandial glycaemic curve when guar was eaten with a standardized test meal. Total plasma cholesterol decreased from 5.79 +/- 0.29 to 5.19 +/- 0.22 mmol/l (p less than 0.05) after the guar treatment period. Guar ingestion reduced postprandial insulin and enteroglucagon responses, the latter significantly so, but had no apparent effect on gastric inhibitory polypeptide, pancreatic glucagon, gastrin, and pancreatic polypeptide.

Adult↗
PubMedDate not supplied

The role of eicosanoids in the process of adaptation following massive bowel resection in the rat.

BACKGROUND: Long chain polyunsaturated fatty acids (LCPUFAs) such as arachidonic acid (AA) and eicosapentaenoic acid (EPA) stimulate intestinal adaptation. Prostaglandins also enhance intestinal adaptation. The purpose of this study was to determine by which eicosanoid pathway dietary arachidonic acid enhances intestinal adaptation. Cyclo-oxygenase or lipoxygenase were selectively inhibited to determine whether either of them enhanced or inhibited adaptation. METHODS: Sixty Sprague-Dawley rats were divided into 2 groups, one receiving an 80% small bowel resection and the other receiving a sham operation. Rats were further divided into groups receiving either a placebo, a general lipoxygenase inhibitor (nordihydroguaiaretic acid [NDGA] at 40 mg/kg per day), or a cyclo-oxygenase-2 inhibitor (Etodolac at 3 mg/kg per day). Rats were pair-fed a diet containing 30% kcal from fat, primarily consisting of AA. RESULTS: After 14 days, mucosal mass, protein, DNA, and disaccharidase activity were measured in the remaining small intestine. There was a significant decrease in ileal mucosal mass in rats receiving Etodolac and a significant increase in mucosal mass in the duodenum in rats receiving NDGA (both p < .001). Mucosal DNA, protein, and disaccharidase data showed similar trends. CONCLUSIONS: These findings suggest that after small bowel resection, dietary arachidonic acid may facilitate the adaptation process by acting as a substrate for the synthesis of prostaglandins, and not through the derivatives of lipoxygenase such as leukotrienes or thromboxanes.

Adaptation, Physiological↗
PubMedDate not supplied

IV chenodeoxycholate prevents calcium bilirubinate gallstones during total parenteral nutrition in the prairie dog.

BACKGROUND: The purpose of this study was to determine whether IV chenodeoxycholate (CDC) could prevent total parenteral nutrition (TPN)-associated pigmented gallstones in the prairie dog. METHODS: Twelve prairie dogs were divided into two equal groups, each receiving an identical TPN regimen. Each animal received 92 kcal/d with 61% of the calories from carbohydrate. The total volume of infusate delivered to each animal was 59 mL/d. Animals in one group, termed the TPN + CDC group, received a daily bolus injection of CDC at a dose of 15 mg/kg. Prairie dogs in the second group, termed the TPN group, received water (vehicle carrier) 1 mL/kg/d. The TPN and TPN + CDC groups received TPN for 40.3 +/- 1.3 and 42.5 +/- 0.6 days, respectively. RESULTS: There was no statistical difference in the initial and final weights between the two groups. None of the TPN + CDC-treated animals had gallstones or calcium bilirubinate crystals. In contrast, all of the TPN-treated animals had calcium bilirubinate crystals (p = .002), and five of six had macroscopic black pigmented gallstones (p = .015). Cholesterol crystals were not observed in either group of animals. The amount of biliary bilirubin and ionized calcium was significantly greater in the TPN group (both p < .001); however, both groups had a similar total biliary calcium concentration. CONCLUSION: IV CDC is effective in preventing TPN-associated gallstones in the prairie dog.

Animals↗
PubMedDate not supplied

Luminal short-chain fatty acids and postresection intestinal adaptation.

BACKGROUND: Short-chain fatty acids (SCFAs) reportedly have a trophic effect on the small intestine. However, it is unclear if this is a local or primarily systemic effect. Loss of the ileocolonic junction (ICJ) may result in increased SCFAs and bacteria in the small intestine from colonic reflux. Our aim was to evaluate the effect of bypass of the ICJ on intestinal SCFA content and postresection adaptation. METHODS: Thirty dogs were studied: transection control (TC, n = 10), distal resection of 50% intestine (DR, n = 10), and distal resection with bypass of ICJ (DRBP, n = 10). Animals were killed at 4 and 12 weeks. Luminal SCFAs and bacteria and adaptation of the small intestine were evaluated. RESULTS: Caloric intake was significantly less in the two resected groups (67 +/- 3 DR and 63 +/- 3, DRBP vs 78 +/- 5 kcal/kg/d TC, p < .05). Body weight and albumin levels were decreased at 12 weeks but were similar between the resected groups (81% +/- 3% and 74% +/- 6% initial and 1.9 +/- 0.1 and 2.1 +/- 0.2 g/dL, DR and DRBP, respectively). Steatorrhea was present for 12 weeks after resection and was greater after DRBP (14.2% +/- 3.8% vs 8.6% +/- 1.9% at 4 weeks and 13.6% +/- 2.5% vs 6.7% +/- 0.6% at 12 weeks, p < .05). Bypassed animals had elevated intraluminal SCFA content (3126 +/- 1094 vs 1791 +/- 538 DR and 1600 +/- 446 micrograms/mL TC, p < .05) and anaerobic bacterial counts (100% vs 50% and 44%, respectively). Tissue inflammation and myeloperoxidase activity were similar. Small intestinal length (174 +/- 10 and 180 +/- 10 cm) and circumference (5.2 +/- 0.4 and 5.2 +/- 0.3 cm) increased to a similar extent in both resected groups at 12 weeks. Thickness of mucosa (1939 +/- 162 vs 1662 +/- 162 microns) and muscle (865 +/- 45 vs 978 +/- 79 microns) layers were similar after DR and DRBP. CONCLUSION: (1) Bypass of the ICJ after distal resection results in increased growth of anaerobic bacteria and luminal SCFA and is associated with more marked steatorrhea. (2) Bypass of the ICJ does not influence structural adaptation of the small intestine. (3) These findings do not support a local trophic effect for SCFA.

Adaptation, Physiological↗
PubMedDate not supplied

Effects of portal vein stenosis and superior mesenteric vein ligation on mesenteric venous pressure and porta-systemic shunting in the rat.

We studied the relative contributions of splanchnic congestion and porta-systemic shunting to the maintenance of experimental portal venous hypertension. Three groups of rats were prepared: portal vein-stenosed, superior mesenteric vein-ligated and sham operated. Though elevated in both operated groups compared to controls, mesenteric venous pressure was highest in the portal vein-stenosed animals (PV vs SMV vs Sham: 19.6 +/- 1.3 vs 15.6 +/- 0.7 vs 13 +/- 0.6; p < .05 PV and SMV vs Sham, and PV vs SMV) despite the presence of 50% porta-systemic shunting in the portal vein-stenosed animals. Shunting was negligible in the other two groups. Peripheral plasma glucagon and vasoactive intestinal peptide (VIP) levels were similar in all three groups. We conclude that mesenteric congestion alone plays a minor role in the pathogenesis of portal hypertension, which may instead be related to the porta-systemic shunting of vasoactive substances other than glucagon and VIP.

Animals↗
PubMedDate not supplied

Blockade of cyclooxygenase-2 inhibits proliferation and induces apoptosis in human pancreatic cancer cells.

Cyclooxygenase (COX), also referred to as prostaglandin endoperoxide synthase, is a key enzyme in the conversion of arachidonic acid to prostaglandins and other eicosanoids. Epidemiologic, animal and in vitro observations show a positive correlation between the expression of COX (especially COX-2) and colonic cancer development, growth and apoptosis. Constitutive expression of COX-2 in human pancreatic cancer cells was recently reported. To evaluate the potential role of COX in pancreatic cancer, RT-PCR was used to determine the constitutive expression of COX-2 in four pancreatic cancer cell lines. MiaPaCa2, PANC-1, HPAF, ASPC-1. The effect of COX blockade with either the general COX inhibitor, indomethacin, or the specific COX-2 inhibitor, NS-398, on [3H]-thymidine incorporation and cell number was investigated in these four pancreatic cancer cell lines. In addition, the effects of these COX inhibitors on pancreatic cancer cell apoptosis was evaluated by DNA propidium iodide staining and the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) assay. All four human pancreatic cancer cell lines expressed COX-2 and their proliferation was concentration- and time-dependently inhibited by both indomethacin andNS398. Substantial apoptosis was also induced by treatment of pancreatic cancer cells with either indomethacin or NS398, as indicated by both DNA propidium iodide staining and the TUNEL assay. Furthermore, indomethacin and NS398 were equipotent for growth inhibition and induction of apoptosis, indicating that eicosanoid synthesis via COX-2 is involved in pancreatic cancer cell proliferation and survival. In conclusion, these findings suggest that the COX pathway, especially COX-2, contributes to the growth and apoptosis of pancreatic cancer. Specific COX-2 inhibitors are likely to be valuable for the treatment and prevention of this deadly cancer.

Antineoplastic Agents↗
PubMedDate not supplied

Plasma and tissue alterations of peptide YY and enteroglucagon in rats after colectomy.

Peptide YY (PYY) and enteroglucagon are produced by endocrine cells of the colonic mucosa. PYY inhibits upper gastrointestinal motility, and enteroglucagon is trophic for small bowel mucosa. Adaptive increase in the production and release of these peptides may improve functional results after colorectal resections. We hypothesized that if segments of the colon were resected, then production and release of PYY and enteroglucagon would increase in the remaining segments of bowel. Animals which underwent colonic transections and partial resections had transient elevations of PYY up to 250 +/- 80 pmol/L, which dropped to control group levels in the second week following surgery. Rats with an abdominal colectomy had significantly greater PYY levels than all other groups from the third (208 +/- 30 pmol/L) to the thirty-eighth (100 +/- 16 pmol/L) week of the study. Circulating levels of enteroglucagon were elevated to 156 +/- 35 pmol/L in rats with a right hemicolectomy during the first week following surgery. Enteroglucagon levels did not significantly vary in the other groups studied. Both tissue PYY (413 +/- 33 pmol/gram) and tissue enteroglucagon (171 +/- 17 pmol/gram) were significantly elevated in the rectums of the rats with an abdominal colectomy, as compared to all other groups. The elevated tissue levels may thus account for the ability to maintain elevated plasma PYY. Double immunogold labeling of endocrine cells in the colorectal tissue for PYY and enteroglucagon revealed both peptides within the same endocrine cells and secretory granules. These studies support the hypothesis that circulating levels of PYY are elevated after major colonic resections and suggest that L-type endocrine cells may participate in adaptive responses which improve intestinal function following colonic surgery.

Animals↗