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Biomedical subjects

T E Adrian

Publications and source records attributed to T E Adrian.

At least 91 records · Page 5Linked to original sources
PubMed1996

Effects of acute and chronic infusion of islet amyloid polypeptide on food intake in rats.

BACKGROUND: Islet amyloid polypeptide (IAPP), also called amylin, is a hormonal peptide produced by the islet beta-cells of the pancreas. Because the peptide is co-stored and co-released with insulin, attention has been focused on IAPP's ability to interfere with glucose metabolism. However, IAPP also has other effects, such as a reduction of food intake. METHODS: In this study we investigated the dose-response effect of acute systemic administration of rat and human IAPP on food intake, and the cumulative effect of chronically increased circulating IAPP concentrations on food intake and body weight in the rat. RESULTS: All doses of rat IAPP investigated acutely inhibited food intake. The lowest infusion rate of 8 pmol/kg/min caused an 28% inhibition of the food intake at 2 h (p < 0.05). No effect of human IAPP was observed. Chronic administration of rat IAPP via an osmotic minipump during a 6-day period caused prolonged inhibitory effects on food intake and reduced body weight. During the first 3 days of infusion the food intake of the IAPP group was only 44% of the food intake of the control group (p < 0.001). The body weight of the IAPP group had fallen 18.6 +/- 2.7 g by day 3, in contrast to a small increase in the control group (4.0 +/- 3.1 g; p < 0.001). The reduction in food intake was sustained throughout the last 3 days of study (IAPP, 16.7 +/- 1.1 g/day; control, 20.6 +/- 1.5; p < 0.05). Similarly, the body weight still differed at the end of day 6 and, compared with day 0, was -8.7 +/- 3.7 g for the IAPP group and +10.9 +/- 4.8 for the control group (p < 0.01). CONCLUSIONS: These findings show that chronic increase of circulating IAPP levels can cause a marked reduction in both food intake and body weight and, together with the reduced food intake seen after acute administration of the peptide, indicates the possibility of IAPP functioning as a satiety factor.

Amyloid↗
PubMed1996

Peptide YY: a potential proabsorptive hormone for the treatment of malabsorptive disorders.

Peptide YY (PYY) is a 36 amino acid peptide that is released from the endocrine cells of the distal ileum, colon, and rectum following a meal. PYY is strongly proabsorptive in the small intestine. We studied the effects of intravenous PYY on colonic water and electrolyte transport in awake dogs. Dogs had 20 cm neurovascularly intact colon Thiry-Vella fistulas (TVS) surgically constructed. Colonic transport was studied in three experimental groups. Group 1 animals received a standard mixed meal. Group 2 animals were unfed and received intravenous PYY and 100 pmol/kg/hr for two hours. This dose of PYY has previously been shown to simulate the plasma levels of PYY normally seen after a meal. Group 3 received intravenous PYY at the same dose in addition to a mixed meal. Our study shows an increase in colonic water, Na+, and Cl- absorption after a meal (P < 0.05). Infusion of PYY at a 100 pmol/kg/hr was significantly proabsorptive beginning at 60 minutes (P < 0.01). Infusion of PYY in addition to a meal further increased absorption (P < 0.05). PYY is a potent proabsorptive agent in the colon of the conscious dog. PYY, or its analogs, may be useful clinical agents in intestinal malabsorptive disorders or after bowel resection.

Animals↗
PubMed1995

Radioimmunoassay of the APC gene product using antibodies against its middle and carboxyl regions.

A radioimmunoassay (RIA) has been developed for the adenomatous polyposis coli protein (APC). High-avidity rabbit polyclonal antibodies were produced against synthetic peptides corresponding to amino acids 1865-1881 (APC-1) and to amino acids 1336-1350 (APC-2) in APC's 2844 amino acid sequence. Both antibodies were utilized in RIA to evaluate full-length APC that is present in the insoluble particulate fraction of cell lysates. High salt extraction, often employed for coiled-coil type protein preparations, was found to be useful for extraction of APC from lysates of normal colonic epithelium. Proteolytic digestion of high salt extracts increased antibody reactivity toward both epitopes, suggesting that APC-1 and APC-2 antigenic sites are partially concealed due to APC's involvement in multiprotein complexes. Thus, RIA using our antibodies will provide a valuable tool for APC protein purification and in studies for elucidating APC's biologic function.

Adenomatous Polyposis Coli Protein↗
PubMed1995

Effect of reversed intestinal segments on intestinal structure and function.

Our aim was to evaluate the short-term effect of a reversed segment on structural and functional intestinal adaptation. Ten dogs underwent 75% distal resection and serosal electrode placement with (RS, n = 5) or without (RO, n = 5) reversal of the terminal 10 cm of the remnant. Nutritional status, absorption, motility, hormonal response, and remnant adaptation were studied at 4, 8, and 12 weeks. Both groups lost weight (RO 89 +/- 3% and RS 76 +/- 8% of initial wt at 12 weeks). Hypoalbuminemia occurred in the RS animals (2.5 +/- .4 vs 2.9 +/- 4 g/dl, P < 0.05). Caloric intake was lower in RS animals during the first 2 weeks. Stool weight increased transiently (4 and 8 weeks) after RO (239 +/- 92 and 249 +/- 25 g/day vs 101 +/- 42 g/day, preop, P < .05) but not RS. Stool fat was elevated in both groups. Remnant length increased after RO (90 +/- 16 to 110 +/- 21 cm) but not after RS (89 +/- 8 vs 86 +/- 9 cm). Morphometric changes were similar. Plasma PYY was increased after RO but not RS animals. Changes in tissue neuropeptides were similar. Intestinal transit time was increased 4 weeks after RS (19 +/- 9 vs 10 +/- 2 min) but was similar to RO thereafter. Myoelectrical activity in the reversed segment was persistently reversed and independent; only 11% of proximal Phase 3 complexes were propagated into the reversed segment. The dominant motor pattern within this segment was orad-migrating clusters and prolonged spike bursts.(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological↗
PubMed1995

Cholecystokinin effect on human lymphocyte ionized calcium and mitogenesis.

Cholecystokinin (CCK) is a peptide present in large amounts in gut, brain, and neurons innervating lymphatic tissues. Plasma CCK levels increase in enterally alimented patients. Enteral alimentation is also associated with enhanced immune function. The effects of CCK and a CCK antagonist were studied on human peripheral blood mononuclear cells (H-PBMC), lymphocyte intracellular ionized calcium ([Ca2+]i), and lymphocyte mitogenesis. CCK receptors transduce their signal via the release of [Ca2+]i. CCK octapeptide caused a specific increase in [Ca2+]i measured by Fura-2 fluorometry in H-PBMC and human T helper lymphocytes. Neither gastrin-17 nor pentagastrin produced a signal. While the highly specific CCK antagonist MK329 blocked the CCK [Ca2+]i signal, it had no effect on the PHA-mediated signal. At high dosages (10(-7)-10(-8) M), CCK was a comitogen with "complete" lymphocyte mitogens such as anti-CD3 monoclonal antibody (mAb) or low-dose PHA, but not for "partial" mitogens such as phorbol esters. CCK comitogenic effect occurred even in the presence of cyclosporine. CCK radioimmunoassay demonstrated that H-PBMC contained CCK and that anti-CD3 mAb- or PHA-mediated H-PBMC mitogenesis caused release of CCK. MK329 blocked PHA and anti-CD3 mAb mitogenesis and CCK comitogenic effects. We conclude that CCK octapeptide may be a coregulator of lymphocyte Ca2+ activation signals. The immunologically beneficial effect of enteral nutrition may, in part, be mediated by increased levels of CCK.

Benzodiazepinones↗
PubMed1995

Somatostatin inhibits B-cell secretion via a subtype-2 somatostatin receptor in the isolated perfused human pancreas.

Recently five somatostatin receptor subtypes (SSTR) have been cloned, allowing the development of highly specific selective agonists for these SSTR. The present study was undertaken to determine which SSTR is responsible for the inhibitory effect of somatostatin on islet hormone secretion. Single-pass perfusion of four agonists was performed in pancreata obtained from four cadaveric organ donors using a modified Krebs-media with 3.9 mM glucose. Sequential 10-min specific receptor agonist infusions (5 ng/ml) of DC32-87 (SSTR2), DC25-12 (SSTR3), DC32-97 (SSTR3), or DC32-92 (SSTR5) were performed in random order separated by 10-min basal periods. Infusion of SSTR2 agonist into the isolated perfused human pancreas resulted in a significant inhibition of insulin and C-peptide secretion (insulin = -1468 +/- 480 pM, P < 0.05, and C-peptide = -2328 +/- 437 pM, P < 0.05) but not islet amyloid polypeptide or somatostatin. These results suggest that the inhibitory effect of somatostatin on B-cell secretion is mediated through the subtype-2 receptor within the human islet.

Adolescent↗
PubMed1995

Establishment and characterization of a new, spontaneously immortalized, pancreatic ductal cell line from the Syrian golden hamster.

Spontaneously immortal pancreatic cell lines are not available. By use of a defined culture medium, such a line (TAKA-1) was established from the Syrian golden hamster. Cytological, cytogenetic, molecular biological, enzymatic and receptor patterns as well as antigenicity were studied and were compared with those of the normal hamster pancreatic ductal cells in vivo. TAKA-1 cells grew exponentially in a monolayer on collagen gel in a defined medium but did not proliferate in soft agar. Ultrastructurally, the cells closely resembled the normal hamster pancreatic ductal cells. Similarities and dissimilarities were found between the normal ductal cells and TAKA-1 cells. Similarities included the presence of cytokeratin, carbonic anhydrase and some tumor-associated antigens. However, unlike the normal ductal cells, TAKA-1 cells expressed blood group A antigen and anti-vimentin, showed affinity to selected lectins, and an abnormality of chromosome 3, which is suggested to be associated with immortality. Moreover, unlike the hamster pancreatic ductal cancer cells but like the normal hamster pancreatic ductal cells, TAKA-1 cells did not have a c-Ki-ras mutation. EGF, TGF-alpha and secretin, but not CCK or GRP, bound to the TAKA-1 cells. TAKA-1 cells produced TGF-alpha, and their growth was stimulated by exogenous EGF in serum-free medium. This cell line presents a suitable model for biologic and pathologic study of the hamster pancreatic ductal cells in vitro.

Animals↗
PubMed1995

Free radical scavengers prevent reflux esophagitis in rats.

Free radical damage in reflux esophagitis of rats induced by 24-hr duodenojejunal ligation was studied. Oxygen free radicals were selectively blocked. Groups were: sham operation, reflux, reflux + superoxide dismutase (SOD), catalase, dimethylthiourea, allopurinol, and inactivated SOD or inactivated catalase alone or in the combination SOD + catalase or SOD + catalase + dimethylthiourea + allopurinol. Macroscopic esophagitis was inhibited only by SOD, alone or in combination with other agents. Esophageal mucosal lipid peroxidation was 10-fold increased in the reflux group compared to the sham group (P < 0.05). This response was damped by SOD > catalase (P < 0.05) but not by the inactivated enzymes, dimethylthiourea or allopurinol. SOD + catalase showed no significant improvement on SOD alone. Total inhibition of lipid peroxidation was achieved by combining all scavengers. Total glutathione (GSH) in the esophageal mucosa was stimulated by reflux. This response was inhibited by scavengers equivalent to their efficacy in preventing lipid peroxidation. It is concluded that reflux esophagitis is associated with free radical release with O2- being the main source. Free radicals appear to stimulate GSH production in this prolonged oxidative stress.

Animals↗
PubMed1995

Esophagitis in Sprague-Dawley rats is mediated by free radicals.

Free radical-mediated esophagitis was studied during duodenogastroesophageal reflux (mixed reflux) or acid reflux in rats. The influence of reflux on esophageal glutathione levels was also examined. Mixed reflux caused more gross mucosal injury than acid reflux. Gross mucosal injury occurred in the mid-esophagus. Total glutathione (GSH) in the esophageal mucosa of control rats was highest in the distal esophagus. The time course of esophageal GSH in rats treated by mixed reflux showed a significant decrease 4 hr after initiation of reflux, followed by a significant increase from the 12th hour on. Mucosal GSH was increased in both reflux groups after 24 hr but significantly more so in the mixed than in the acid reflux group. The free radical scavenger superoxide dismutase (SOD) prevented esophagitis and was associated with decreased GSH levels. GSH depletion by buthionine sulfoximine (BSO) prevented esophagitis and stimulated SOD production in the esophageal mucosa. It is concluded that gastroesophageal reflux is associated with oxidative stress in the esophageal mucosa. The lower GSH levels in the mid-esophagus may predispose to damage in this area. Duodenogastroesophageal reflux causes more damage than pure acid reflux. Oxidative stress leads to GSH depletion of the esophageal mucosa in the first few hours following damage but then stimulates GSH production. GSH depletion by BSO does not worsen esophagitis since it increases the esophageal SOD concentration.

Animals↗
PubMed1995

Glucagon, stress, and portal hypertension. Plasma glucagon levels and portal hypertension in relation to anesthesia and surgical stress.

Glucagon has been proposed as the mediator of splanchnic hyperemia in portal hypertension. Employing an assay specific for pancreatic glucagon, we reevaluated the relationship between this peptide and portal hypertension in the portal vein (PV)-stenosed rat model addressing, in particular, the effects of anesthesia and surgical stress. Plasma glucagon levels were similar in sham-operated and portal hypertensive rats: glucagon, sham vs PV stenosed: 110.7 +/- 17.1 pmol/liter vs 140.6 +/- 23.3 pmol/liter (NS). Furthermore, plasma levels of glucagon and the related peptide VIP were not significantly influenced by anesthesia or surgical stress, and levels remained similar under all conditions in sham-operated and PV-stenosed animals. We conclude that pancreatic glucagon is not elevated in the PV-stenosed rat; differences between these results and those describing hyperglucagonemia in this model cannot be explained on the basis of a differential response to stress but may reflect differences in glucagon assay system.

Anesthesia↗
PubMed1995

Effect of protease inhibitors on peptide-stimulated amylase secretion from dispersed pancreatic acini.

Cholecystokinin (CCK) and bombesin stimulate dose-dependent amylase secretion from dispersed pancreatic acini. To establish whether cellular proteases can reduce secretion by degrading these regulatory peptides, the effect of protease inhibition on CCK and bombesin stimulated amylase secretion was investigated. A spectrum of protease inhibitors, including bacitracin, phenylmethylsulfonylfluoride, captopril, bestatin, phosphoramidon, and 1,10-phenanthroline, were investigated. Bacitracin (0.35 mM) increased the acinar amylase secretory response to CCK and bombesin substantially, suggesting that these two peptides are degraded by an endopeptidase from pancreatic acinar cells. In contrast, PMSF (1 mM) inhibited CCK and bombesin stimulated amylase release, suggesting a covalent interaction with this inhibitor and CCK or bombesin receptors. Other protease inhibitors either had minimal or no effects on acinar cell secretion. These results suggest bacitracin is a valuable enzyme inhibitor that can potentiate the effect of CCK and bombesin on acinar cells. In contrast, PMSF should be avoided when using these secretagogs to study pancreatic function.

Amylases↗
PubMed1995

Carboxyfluorescein and biotin neuromedin C analogues: synthesis and applications.

Two neuromedin C (NC) analogues were constructed by Fmoc synthesis and in situ coupling of 4(5)-carboxyfluorescein or biotin to the N-terminus. Both displayed full agonism in an amylase release assay and cross-reacted fully with a NC-specific antiserum. Biotin NC functioned in a streptavidin-capture ELISA. Carboxyfluorescein NC was used to probe receptor localization in rat stomach. Specific NC binding sites, which did not interact with substance P, angiotensin I, or neurokinin A, were labeled in the antrum. Identity of NC binding sites was confirmed by microautoradiography. The specifically labeled cells were all found in the lamina propria and at least some of cells were identified as eosinophils.

Amylases↗
PubMed1995

Effect of intestinal tapering and lengthening on intestinal structure and function.

BACKGROUND: Intestinal lengthening (TL) is increasingly performed for the short bowel syndrome. Our aim was to evaluate the effect of TL on canine intestinal structure and function. METHODS: Two groups of 5 dogs had 75% distal intestinal resection. Twelve weeks later, serosal electrodes were placed in one group (RO) and tapering and lengthening of 10 to 15 cm distal intestine and electrode placement was performed in the other group (TL). Nutritional status and intestinal absorption, motility, and hormone release were assessed every 4 weeks for 12 weeks after the second procedure. RESULTS: The animals with the lengthening had diminished body weight (75% +/- 2% versus 81% +/- 4%, P < 0.05) and albumin levels (2.4 +/- 0.2 g/dL versus 2.9 +/- 0.5 g/dL, P < 0.05) and impaired absorption (stool fat 18% +/- 6% versus 10% +/- 3%, P < 0.05) compared with those that had undergone resection alone. The intestinal adaptive response was blunted in the TL group (villus height 328 +/- 90 microns versus 410 +/- 36 microns, P < 0.05). Transit time was prolonged 4 and 8 weeks (19 +/- 6 min and 18 +/- 5 min, respectively, versus 11 +/- 3 min, P < 0.05) after TL. Myoelectrical recordings showed a drop in slow wave frequency and impaired migration of Phase III of the migrating motor complex within the tapered and lengthened segments (P < 0.05). Both fasting and postprandial serum gastrin levels were two times greater in the TL group (P < 0.05). Enteroglucagon levels were increased after resection alone; this increase was attenuated by more than 50% in the TL group (P < 0.05). The somatostatin response to feeding was substantially greater in the TL animals. CONCLUSIONS: TL impairs nutritional status and intestinal absorption and adaptation following massive resection. The changes in absorption and transit may be related, in part, to motor disruption and hypergastrinemia. The impaired adaptation is possibly related to decreased enteroglucagon and increased somatostatin levels.

Animals↗
PubMed1995

The effects of a new amino-acid dipeptide solution on nitrogen balance and humoral growth factors in the postoperative state in man.

27 patients admitted for elective abdominal surgery were allocated to receive postoperative total parenteral nutrition supplemented with glutamine (glycyl-glutamine) and tyrosine (glycyl-tyrosine) containing dipeptides (DP-Gln 20; 0.16 g glutamine/kg BW/24 h) or isonitrogenous Vamin 18 for 5 days. The aim was to evaluate safety and effects on short-life plasma proteins, nitrogen balance, 3-methylhistidine excretion and alimentary growth factors in plasma. No differences in transthyretin or retinol binding protein levels, nitrogen balance or 3-methylhistidine excretion were found in patients receiving DP-Gln 20 compared to Vamin 18. There were higher plasma levels of peptide YY in the dipeptide group 5 days after surgery (p < 0.05). A correlation between insulin levels and nitrogen balance was found only in DP-Gln 20 treated patients day 6 (r = 0.91, p < 0.01). DP-Gln 20 is a glutamine dipeptide (Gly-Gln) containing amino acid solution which is considered safe in the postoperative state in man. No beneficial effects on whole body protein metabolism were found by adding DP-Gln 20 to total parenteral nutrition.

Journal Article↗