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Biomedical subjects

V L Go

Publications and source records attributed to V L Go.

At least 127 records · Page 7Linked to original sources
PubMed1986

Lack of a direct effect of the autonomic nervous system on glucose-stimulated gastric inhibitory polypeptide (GIP) secretion in man.

To determine whether the autonomic nervous system has a direct effect on GIP secretion, six normal subjects received a 4-hr intraduodenal perfusion of glucose (225 mg/min) and polyethylene glycol on four successive days. During the latter 2 hr, either normal saline, propranolol, phentolamine, or atropine were infused intravenously. Glucose absorption was calculated by measuring glucose and polyethylene glycol following luminal aspiration distal to the perfusion site. Basal and peak or nadir values in the saline study of plasma glucose, insulin, glucagon, and GIP were similar to the other three studies prior to autonomic blockade. During the latter 2 hr of the glucose perfusion, the plasma glucose and glucagon responses to saline did not differ from responses to the three blocking agents. Phentolamine but not atropine or propranolol resulted in a greater insulin response compared to saline (3247 +/- 762 vs 1348 +/- 388 microU/ml/120 min, P less than 0.01). GIP was not significantly affected by phentolamine (18,146 +/- 4574), propranolol (7585 +/- 5854), or atropine (15,797 +/- 6297) compared to saline (11,717 +/- 5204 pg/ml/120 min). Glucose absorption was unaffected by infusions of saline, phentolamine, and propranolol, but was increased following atropine infusion (5841 +/- 1120 vs 1044 +/- 808 mg/120 min, P less than 0.02). There appears to be no direct effect of the autonomic nervous system on glucose-induced secretion of GIP.

Adult↗
PubMed1986

Gastrointestinal regulatory peptides modulate in vitro immune reactions of mouse lymphoid cells.

The effects of six gastrointestinal regulatory peptides (beta-endorphin, substance P, metenkephalin, vasoactive intestinal peptide, bombesin, and somatostatin) on mouse lymphocytes stimulated with concanavalin A, lipopolysaccharide, phytohemagglutinin, or alloantigens were evaluated. Lymphocytes were stimulated in vitro and the influences of exogenously adding varying concentrations of neuropeptides (10(-6)-10(-11) M) on the incorporation of [methyl-3H-]thymidine were determined. The roles of cell density and antigen concentration on neuropeptide induced immunomodulation were also assessed. We observed that vasoactive intestinal peptide (VIP) would significantly inhibit the response of B10 lymphocytes to concanavalin A (54%) and phytohemagglutinin (56%) but not to lipopolysaccharide (16%). The VIP-induced inhibition was progressively diminished as the neuropeptide concentration was reduced to 10(-11) M. By 24 hr after stimulation the lymph node cells were refractory to the inhibitory effects of VIP. In addition, VIP would not inhibit B10 lymph node cells from responding to B10. K spleen cells in mixed, one-way lymphocyte cultures. The other five peptides did not influence the in vitro responses. The potential role of neuropeptides in the pathophysiology of immunologic-based disorders is discussed.

Animals↗
PubMed1986

Intracerebroventricular injections of cholecystokinin octapeptide suppress feeding in rats--pharmacological characterization of this action.

Cholecystokinin octapeptide (CCK-8), administered intracerebroventricularly (i.c.v.), will suppress feeding. The aim of the present study was to determine the pharmacological characteristics of this satiety inducing effect in rats. For this purpose, we employed a feeding bioassay model in 24 h fasted rats and examined the effects of CCK-8 and a variety of structurally related analogs on latency to feed after i.c.v. injection and on the amount of food and water consumed as measured after the initiation of feeding in sequential 20-min epochs for 1 h. CCK-8, given in doses of 0.1, 1 and 10 nmol, produced a dose-dependent increase in feeding latency and a reduction of food intake during the first 20 min after initiation of feeding. Food intake during the next 40 min and water consumption were not altered. Plasma levels of CCK-like immunoreactivity after an i.c.v. injection of a dose of CCK-8 which blocked feeding (10 nmol) rose insignificantly from 117 to 125 pg/ml. In contrast, at the minimally effective dose of CCK-8 after i.v. administration (10 nmol), which also produced an inhibition of feeding, the plasma level was 1430 pg/ml. This difference indicates that plasma levels of CCK after i.c.v. CCK-8 are not adequate to produce the observed feeding suppression and suggests that the effects of i.c.v. CCK-8 are not mediated by a peripheral redistribution. Systematic dose response studies revealed the following rank order of potencies: CCK-8 greater than or equal to G-17 II much greater than CCK-8 NS = G-17 I greater than or equal to CCK-4 = CCK 26-29 = 0. Only gastrin-17 II (sulfated) produced an effect comparably significant to CCK-8. I.c.v. proglumide at 2500 nmol failed to modify the effects of CCK-8 at 10 nmol after i.c.v. injection. These data demonstrate that the structural requirements for feeding suppressive activity in rat brain are the carboxyterminus with a sulfated tyrosine residue, located 6 to 7 residues from the carboxyterminus, as present in CCK-8 and gastrin-17 II.

Animals↗
PubMed1986

Substance P distribution and effects in the canine epicardial coronary arteries.

Substance P (SP), a vasoactive neuropeptide detected in animal and human hearts has been reported to increase coronary blood flow in animals. However, no data are available on SP effects on epicardial coronary arteries, the site of coronary disease. To determine the amount and distribution of SP and its action in the large coronary vessels, we studied two groups of dogs. One group was anesthetized for collecting three 1 cm segments of the circumflex coronary artery (CX) and left anterior descending artery (LAD) through a left thoracotomy. These segments represented proximal (I), middle (II), and distal (III) portions of the two arteries. Concentrations (ng/g) of SP-like immunoreactivity (SP-LI) were determined by radioimmunoassay. SP-LI was present in LAD (I: 1.17 +/- 0.20, II: 1.08 +/- 0.36, III: 1.14 +/- 0.25) and CX (I: 1.44 +/- 0.38, II: 1.51 +/- 0.47, III: 0.70 +/- 0.20). SP differences among segments of LAD and segments I and II of CX were not significant, but there was a significant difference between segment III of CX and the others. In the second group of closed chest anesthetized dogs, we examined the effects of intracoronary SP infusion before and during administration of serotonin (5HT). LAD and CX artery responses (% area change) to SP and to SP plus 5HT were examined using quantitative coronary angiography. Intracoronary 133Xe in saline provided coronary flow data. SP infusion produced significant vasodilation in segment II (15% area increase) and III (17%) during the highest dose (1 microgram/min). The three SP doses infused with 5HT (0.05 mg/min) did not produce vasodilation, although LAD segment III constriction from 5HT was abolished during the highest dose of SP infusion. The presence of SP, and its dilatory effect on the coronary arteries, suggests a role in maintaining vasodilator tone in the coronary arteries.

Animals↗
PubMed1986

Neurotensin in diabetes and obesity.

Basal and postprandial concentrations of immunoreactive neurotensin were measured in insulin dependent diabetic patients and lean and obese noninsulin dependent diabetic patients when partially withdrawn from subcutaneous (s.c.) insulin treatment and again when near normoglycemia had been achieved from insulin infusion by an artificial endocrine pancreas (AEP). Neither basal nor postprandial neurotensin differed among the 3 groups of diabetic patients during s.c. insulin treatment nor from weight matched nondiabetic subjects. In addition, AEP resulted in no significant change in postprandial neurotensin responses. No differences in neurotensin levels were observed between lean and obese nondiabetic subjects. In contrast to observations in experimental diabetes, these observations do not support the presence of an abnormality of neurotensin in human diabetes.

Blood Glucose↗
PubMed1986

Action and localization of vasoactive intestinal peptide in the coronary circulation: evidence for nonadrenergic, noncholinergic coronary regulation.

Vasoactive intestinal polypeptide, a neurotransmitter peptide detected in animal and human hearts, has been found in nerves of coronary arteries. To determine the amount and distribution of vasoactive intestinal polypeptide in the large coronary vessels and its possible participation in coronary vasoregulation, two groups of animals were studied. In the first group, 11 anesthetized dogs were sacrificed to collect three (1 cm) segments along the circumflex and left anterior descending coronary arteries. These segments represented proximal (I), middle (II) and distal (III) portions of the two arteries. Concentrations (ng/g) of vasoactive intestinal polypeptide-like immunoreactive substance were determined by radioimmunoassay. Vasoactive intestinal polypeptide-like immunoreactivity was present in the left anterior descending (I = 7.28 +/- 1.65, II = 3.74 +/- 0.57, III = 2.29 +/- 0.53) and circumflex (I = 4.16 +/- 1.52, II = 4.58 +/- 1.13, III = 4.00 +/- 0.81) coronary arteries. The difference in vasoactive intestinal polypeptide-like immunoreactivity among epicardial segments of the anterior descending artery was significant, but there was no significant difference among segments of the circumflex coronary artery. In the second group (eight closed chest anesthetized dogs), the effects of vasoactive intestinal polypeptide intracoronary infusion on epicardial coronary constriction were examined at rest and with the artery constricted by serotonin. Left anterior descending (segments I, II and III) artery responses (% area change) to vasoactive intestinal polypeptide and vasoactive intestinal polypeptide plus serotonin were examined using quantitative coronary angiography. Vasoactive intestinal polypeptide infusion resulted in significant vasodilation in all the segments (I, II and III) of the left anterior descending artery.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

The acute effects of coffee and caffeine on human interdigestive exocrine pancreatic secretion.

The effects of coffee on exocrine pancreatic secretion are unknown but may be important, because a link between chronic stimulation of pancreatic secretion and experimental chemical carcinogenesis and an association between coffee drinking and human pancreatic adenocarcinoma have been reported. We measured exocrine pancreatic trypsin and gastric acid secretions collected through orogastroduodenal tubes and serum gastrin in eight non-coffee drinkers and eight coffee drinkers. During fasting, after one interdigestive cycle control period, one of four 250-ml samples [plain water, water plus caffeine (4.6 mg/kg), decaffeinated coffee (127.9 mg/kg), caffeinated coffee (127.9 mg/kg)] was administered through the orogastric tube. Caffeinated and decaffeinated coffee (p = 0.008), caffeine (p = 0.03), and an unidentified substance(s) in coffee other than caffeine (p = 0.008) were associated with increased interdigestive exocrine pancreatic trypsin secretion. In addition, we also confirmed that coffee and caffeine stimulated gastric acid secretion (p = 0.02) and decaffeinated coffee raised serum gastrin concentrations (p = 0.005). If an association between coffee and pancreatic carcinogenesis exists, chronic stimulation of the exocrine pancreas by secretagogues could result in a gland susceptible to carcinogenesis.

Adenocarcinoma↗
PubMed1986

Large molecular forms of cholecystokinin circulating in humans.

Molecular heterogeneity between cholecystokinin (CCK) present in humans and that present in the pig has been proposed. We recently demonstrated that CCK-8 exists in humans in form identical to the porcine peptide. The aims of this work were to evaluate the presence in human plasma of CCK forms larger than CCK-8 and to compare them with the well-characterized porcine forms. Antiserum (no. 4899) was raised in a New Zealand white rabbit immunized with porcine CCK-33 that had specificity for the 7 to 21 region of that peptide and that recognized molecules present in human plasma. To characterize these, postprandial human plasma was applied to an immunoaffinity column generated with this antiserum. Adsorbed peptides were eluted, concentrated on an octadecylsilane cartridge, separated by reversed-phase HPLC and gel filtration chromatography, and screened by cross-reacting and specific CCK and gastrin radioimmunoassays and CCK bioassay by quantification of amylase release by rat pancreatic acini. Two peptides were consistently identified that possessed CCK-like but not gastrin-specific immunoreactivity and CCK-like biological activity. These appeared to be similar in size to CCK-33 and intermediate in size between CCK-33 and CCK-8. Though analogous to porcine CCK based on antibody cross-reactivity and biological activity, the human peptides were heterogeneous from the porcine peptides based on differing chromatographic behavior.

Amylases↗
PubMed1986

Fate of pancreatic enzymes during small intestinal aboral transit in humans.

To determine survival of pancreatic enzymes during small intestinal aboral transit in humans, seven healthy volunteers were intubated with an oroileal tube. By using nonabsorbable markers we measured the cumulative amount of lipase, trypsin, and amylase activities and lipase and trypsin immunoreactivities delivered postprandially to the duodenum, midjejunum, and terminal ileum. We found that as the enzymes moved from duodenum to ileum, 74% of amylase activity, 22% of trypsin activity, and 1% of lipase activity survived transit. Enzymatic activity and immunoreactivity of trypsin and lipase disappeared at different rates, suggesting that for these enzymes the sites of enzymatic activity and immunorecognition are not identical. Since tryptic activity is present even in the absence of immunorecognizable trypsin, complete structural integrity of the trypsin molecule may not be essential for its enzymatic activity. The short intraluminal survival of lipolytic activity may partially explain why patients with progressive exocrine pancreatic insufficiency malabsorb fat earlier than other nutrients.

Adult↗
PubMed1986

Role of glucagon in splanchnic hyperemia of chronic portal hypertension.

The role of glucagon as a blood-borne mediator of the hyperdynamic circulation associated with chronic portal venous hypertension was assessed in the rat portal vein stenosis model. Selective removal of pancreatic glucagon from the circulation was achieved by intravenous infusion of a highly specific glucagon antiserum. Blood flow to splanchnic organs, kidneys, and testicles was measured with radioactive microspheres, and the reference-sample method. Glucagon antiserum had no effect on blood flow in the gastrointestinal tract of sham-operated (control) rats. However, the antiserum produced a significant reduction in hepatic arterial blood flow in the control rats, suggesting that glucagon contributes significantly to the basal tone of hepatic arterioles. In portal hypertensive rats glucagon antiserum significantly reduced blood flow to the stomach (22%), duodenum (25%), jejunum (24%), ileum (26%), cecum (27%), and colon (26%). Portal venous blood flow was reduced by approximately 30%. The results of this study support the hypothesis that glucagon mediates a portion of the splanchnic hyperemia associated with chronic portal hypertension.

Animals↗
PubMed1986

Neurotransmitter modulation of VIP release from cat cerebral cortex.

The cortical release of vasoactive intestinal polypeptide-like immunoreactivity (VIP-LI) in vivo was examined by superfusion of the pial surface of the cerebral cortex of the cat. The modulation of cortical VIP release by several neurotransmitters [gamma-aminobutyric acid (GABA), opioids, norepinephrine, acetylcholine, and glutamate] normally present in the cerebral cortex was studied by administering respective agonists and antagonists for their receptors. Although GABA and opiate agonists did not influence the resting release of VIP-LI, GABA antagonists (picrotoxin and bicuculline) and opiate antagonists (naloxone and naltrexone) significantly elevated the resting release. The evoked release from cortex of VIP-LI (by electrical stimulation of the cortex or mesencephalic reticular formation) was suppressed by GABA and mu- but not delta-, kappa-, or sigma-opioid receptor agonists. Glutamate and kainic acid increased the resting release of VIP-LI from the cerebral cortex. Noradrenergic (alpha 2 but not alpha 1) displayed an inhibitory effect on the evoked release of cortical VIP-LI release. Resting VIP-LI release was enhanced by cholinergic agents (carbachol). The facilitatory effects of mesencephalic reticular formation stimulation on VIP-LI release were demonstrated by atropine. These observations suggest characteristic interactions reflecting the circuitry modulating the activity of cortical VIP-releasing neurons.

Animals↗
PubMed1986

Immunochemical studies of substance P and cholecystokinin octapeptide recovery in dorsal horn following unilateral lumbosacral ganglionectomy.

Deafferentation of the cat lumbosacral dorsal horn following unilateral ganglionectomy (L2-S3) produced an ipsilateral depletion of substance P (sP) and cholecystokinin octapeptide (CCK) immunoreactivity (IR). The loss of sP IR and CCK IR was most marked at 11 days postlesion, and partial recovery of sP IR and CCK IR was noted in the upper laminae of the dorsal horn ipsilateral to the lesion 14 days after deafferentation. The dorsal horn sP IR and CCK IR distribution and density of staining on the deafferented side were indistinguishable from those on the control side 1 month after ganglionectomy. The pattern and density of methionine-enkephalin (M-ENK) IR was not disrupted by deafferentation, demonstrating that the sP IR and CCK IR depletions were due to the deafferentation and not to nonselective vascular damage. The recovery of sP IR and CCK IR was not affected by midline myelotomy or thoracic cord transections, implying a local origin for the recovered sP IR and CCK IR. Moreover, capsaicin, a primary afferent neurotoxin, depleted sP IR and CCK IR only from the intact side. Thus, these studies indicate that the recovery of two immunochemically identified primary afferent transmitters in the dorsal horn does not involve intraspinal sprouting of primary afferents. Radioimmunoassay (RIA) analysis of the ganglionectomies followed by recovery periods ranging from 7 to 28 days confirmed the depletion and recovery of sP IR, but the RIA indicated a temporal shift in depletion and recovery. Maximal depletion was measured at 21 days and recovery was observed at 28 days after unilateral deafferentation.

Afferent Pathways↗
PubMed1986

Gastrointestinal regulatory peptides modulate mouse lymphocyte functions under serum-free conditions in vitro.

Conditions are described for performing mitogen (Concanavalin A, Con A; lipopolysaccharide, LPS) and mixed lymphocyte reaction (MLR) cultures using serum-free medium. The effects of exogenously adding several gastrointestinal regulatory peptides (beta-endorphin, substance P, met-enkephalin, vasoactive intestinal peptide, bombesin and somatostatin) on the incorporation of 3H-methyl-thymidine was determined. It was observed that mitogen stimulation of lymph node cells with Con A was inhibited (70% of control) by vasoactive intestinal peptide (VIP) but spleen cells stimulated by LPS were insensitive to immunomodulation (98% of control). The ability of VIP to inhibit Con A induced thymidine incorporation was concentration dependent (10(-6) to 10(-18) M) and was not attributable to kinetic shifts or cell toxicity. None of the other tested neuropeptides affected Con A or LPS induced blastogenesis. MLR cultures were inhibited by VIP, beta-endorphin and somatostatin in a biphasic manner with maximal inhibition observed at 10(-8) to 10(-12) M. Both substance P and bombesin exhibited slight immunoenhancing properties at 10(-14) to 10(-18) M. Met-enkephalin was ineffective as an immunomodulator of MLR cultures. The utility of using serum-free medium in identifying neuropeptides with immunomodulatory properties are discussed.

Animals↗
PubMed1985

Studies on the in vivo release of vasoactive intestinal polypeptide (VIP) from the cerebral cortex: effects of cortical, brainstem and somatic stimuli.

The release of vasoactive intestinal polypeptide (VIP) from the surface of the sensorimotor (parietal) cortex of anesthetized cats was measured by radioimmunoassay (RIA) procedures. Two types of anesthetics were examined (chloralose-urethane and halothane). Increasing the dose or concentration of anesthetics produced a suppression of electrocortical activity and resulted in a reduction in the resting release of VIP from cerebral cortex. The mean rate of resting release of endogenous VIP in cats anesthetized with chloralose-urethane was 16.8 +/- 4.6 fmol/30 min/cm2 cortex. Although there were differences in the basal levels of VIP-like immunoreactivity (VIP-LI) among different animals, the baseline levels of VIP-LI varied little during the initial period of 6-7 h period of anesthesia with chloralose-urethane (40 and 300 mg/kg). Examination of representative electrocorticography which corresponded with the superfusion period revealed an association between stable levels and a relatively invariant pattern of electrical activity. All experimental manipulations were carried out during the period of stable release. The rate of release was increased by focal, unilateral stimulation of the cerebral cortex both ipsilateral and contralateral to the side of stimulation (3.2 +/- 1.1 and 1.4 +/- 0.5 times the resting release, respectively). Bilateral stimulation of the mesencephalic reticular formation (MRF) produced a frequency-dependent increase in cortical VIP release over the range of 60-100 Hz. Bilateral electrical stimulation of sciatic nerves at intensities that recruit A delta and C fibers failed to consistently increase the release of VIP-LI from the cortex in chloralose-urethane anesthetized cats but did evoke a significant increase of cortical VIP output in cats anesthetized with 1.5 and 1% halothane. Removal of calcium ions from the superfusing fluid and substitution of cobalt (a calcium channel blocker) or EDTA (a calcium chelating agent) for calcium ions did not affect the resting release of endogenous VIP, but attenuated the increase in VIP release normally evoked by electrical stimulation of the cortical surface or MRF. Tetrodotoxin (TTX), which blocks sodium channels and thus blocks the propagation of nerve impulses, did not influence the resting release of VIP. TTX, at concentrations that prevent the increase in VIP release evoked by veratridine, greatly enhanced the surface-stimulated release but abolished the increase in VIP release evoked by MRF stimulation.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1985

Hepatitis B virus replication in steroid-treated severe HBsAg-positive chronic active hepatitis.

To determine the effect of corticosteroids on the replication of hepatitis B virus and to assess the relationship between virus replication and prognosis, the behavior of serum and tissue HBcAg was evaluated in 16 patients with severe HBsAg-positive chronic active hepatitis who were treated with prednisone and followed for up to 10 years (mean +/- SEM, 66 +/- 9 months). Hepatitis B virus replication was assessed in serum by a solid-phase radioimmunoassay of Dane particle-associated HBcAg and in liver tissue by indirect immunoperoxidase staining for HBcAg. Despite the presence of severe inflammatory activity, only low levels of hepatitis B virus replication were demonstrated. Mean serum HBcAg levels were low at accession and remained essentially unchanged or gradually decreased during corticosteroid therapy. Serum HBcAg appeared in only one patient in whom no virus replication was detected prior to therapy. HBeAg was frequently detected at low titers by radioimmunoassay when serum HBcAg was undetectable. Loss of HBcAg preceded loss of HBeAg by radioimmunoassay, and disappearance of both markers was a prerequisite for sustained histologic remission. In eight patients, inflammation was present despite absence of serum or tissue HBcAg; in three of these, disease activity continued after loss of HBeAg. We conclude that low levels of hepatitis B virus replication may be associated with severe inflammatory activity, and these levels are not increased by long-term corticosteroid therapy. Inflammation can continue despite loss of HBeAg and absence of detectable virus replication.

Adrenal Cortex Hormones↗
PubMed1985

Diagnostic and prognostic implications of plasma amino acid determinations in chronic active hepatitis.

To further assess the molar ratio of branched-chain to aromatic amino acids as a measure of disease activity, we correlated results of this test with histologic features of inflammation, standard biochemical tests, and prognosis in 68 patients with severe chronic active hepatitis. An abnormal molar ratio (less than 3.0) reflected histologic findings of chronic active hepatitis in 26 of 35 instances. A normal molar ratio (greater than or equal to 3.0), however, was associated with histologic features of chronic active hepatitis in nine of 14 instances. Molar ratio abnormalities occurred more frequently in patients with cirrhosis than without cirrhosis (95% vs 45%, P less than 0.01). Only one of 20 patients with cirrhosis had a normal ratio, and none of 12 followed serially during therapy improved the ratio to normal. No correlation was seen between the molar ratio and severity of inflammation or serum levels of aspartate aminotransferase, albumin, bilirubin, and gamma globulin. When corticosteroids were discontinued, relapse occurred as frequently in patients with a normal molar ratio as in others (80% vs 71%), and the presence of an abnormal ratio did not preclude a sustained remission after treatment. We conclude that the plasma molar ratio does not reflect histologic activity, correlate with standard liver function tests, or indicate disease behavior after treatment withdrawal. A normal molar ratio during or after treatment, however, may exclude cirrhosis.

Adolescent↗
PubMed1985

Effect of central sympathectomy on gastric and small intestinal myoelectric activity and plasma motilin concentrations in the dog.

Using a canine model, we studied fed and fasting gastric and small intestinal myoelectric activity and plasma motilin concentrations before and after transection of the spinal cord between the second and third thoracic segments. In sham-operated dogs, migrating complexes returned to normal by the second day after operation. Immediately after spinal cord transection, migrating complexes cycled in jejunum and ileum but not in the stomach and duodenum. After 11 and 15 days, migrating complexes returned to the duodenum and stomach, respectively. Plasma motilin concentrations did not cycle in animals without duodenal migrating complexes but returned to a normal cyclical pattern when duodenal migrating complexes returned. Feeding interrupted migrating complexes after cord transection and sham operation. The data observed in animals after 15 days suggest that myoelectric activity in fasted dogs and conversion of the fasted to the fed state of myoelectric activity are not under the control of supraspinal, sympathetic pathways.

Animals↗