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Biomedical subjects

V L Go

Publications and source records attributed to V L Go.

At least 37 records · Page 2Linked to original sources
PubMed1997

Stem cell factor alters membrane potential of purified peritoneal mast cells in culture.

The membrane potential (E(m)) was used as an indicator to evaluate the effect of stem cell factor (SCF) on the membrane integrity of peritoneal mast cells (PMCs). PMCs were harvested from the peritoneal lavage of Sprague-Dawley rats, purified more than 95% and cultured with or without the presence of SCF (2 x 10(-8) M). E(m) values were measured with conventional intracellular recording techniques. Results from day 1 to day 4 in culture were compared. Significant differences in average E(m) (aE(m)) (P < 0.01, analysis of variance) were seen on days 3 and 4 (means +/- SE in millivolts): -67.4 +/- 8.0 and -59.4 +/- 4.8 with SCF vs. -24.8 +/- 7.9 and -7.6 +/- 3.9 without SCF, respectively. Moreover, after culture with SCF for >1 wk, the aE(m) values of purified PMCs had a tendency to reach plateau values similar to that of unpurified PMCs on day 1 (at -20 mV). The morphological appearances of PMCs can be correlated with the results of aE(m) measurements. PMCs with a smooth spherical shape and highly refractive appearance, and better tolerance to electrode impalement, showed E(m) with greater negative values and lesser fluctuations. These results indicate that SCF can maintain the membrane properties and viability of purified PMCs in a long-term culture.

Animals↗
PubMed1997

Two types of leptin-responsive gastric vagal afferent terminals: an in vitro single-unit study in rats.

In vitro gastric vagal afferents' (GVAs) unit activities were recorded from the ventral GVA nerve strands in rats. The responsiveness of 16 GVA terminals to close intra-arterial injection of vehicle (0.1 ml), leptin (350 pmol), and cholecystokinin (CCK)-8 (10 pmol) was analyzed to generate a spike count-versus-time histogram. Data of 5-min spike counts before and after each treatment were normalized by dividing the latter by the former. A quotient (Q) > 1 indicates an excitatory effect, Q < 1 indicates an inhibitory effect, and Q close to 1 indicates no effect. Two types of GVA terminals were identified. Type 1 (n = 8) responded to leptin with Q > 1; CCK-8 pretreatment did not consistently alter leptin sensitivity. In contrast, Type 2 (n = 8) responded to leptin with Q < 1 or close to 1, and CCK-8 pretreatment increased the leptin sensitivity so that the terminals responded to subsequent leptin with Q > 1. These data suggest that Type 1 and Type 2 GVA terminals may provide afferent neural signals, which, in turn, will be involved in body weight and food intake control systems, respectively.

Animals↗
PubMed1995

Centrifugal gastric vagal afferent unit activities: another source of gastric "efferent" control.

Our previous studies indicated that in rats about 10% of ventral gastric vagal efferent discharges do not originate from supracervical neural elements. To determine the origin of these efferent activities, an in vitro subdiaphragmatic vagus nerve-esophagus preparation was used. Action potentials with the same amplitude and waveform, and behaving 'all or none' characteristic are considered to be recorded from a nerve fiber and defined as an unit activity. Because these centrifugal unit activities were recorded from the proximal cut end of the ventral gastric vagal strands, they are ostensibly considered to be efferent activities. However, about 50% of unit action potential samples (21 out of 40) behave like unit activities recorded from mechanoreceptive afferent fibers. They have spot-like or diffuse mechanoreceptive fields on the subdiaphragmatic esophagus. When these receptive fields were stimulated the sensory nerve terminals in the fields generate afferent unit action potentials. These afferent potentials not only propagate orthodromically to the central nerve system, but also can be transmitted centrifugally to the gastric branches of the same vagal afferent neuron. Together with the efferent discharges of gastric vagal motor neurons, these centrifugal sensory potentials can be intercepted from the proximal cut end of gastric vagal nerve strands at gastroesophageal junction. Three types of mechanoresponsive centrifugal afferent unit activities were observed: rapidly adapting (n = 8), with or without after-discharge; slowly adapting (n = 8), with or without after-discharge, and initial high frequency followed by a plateau, with long-lasting after-discharge (n = 5). Of the tested units (n = 24), 25% were either activated or inhibited by esophageal inflation and 23% (n = 22) by esophageal deflation. It is evident that not all centrifugal unit action potentials recorded from the proximal cut end of gastric vagal nerve strands are generated from the vagal motor neurons, the recorded centrifugal unit activities may contain antidromic unit action potentials generated from the esophageal collateral branches of the gastric vagal afferent nerve fibers. These results suggest that gastric vagal afferent neurons possess collateral branches innervating the esophagus, activation of esophageal terminals may exert an effect on the gastric terminals via collateral reflex, analogous to the 'axon reflex' mechanism.

Action Potentials↗
PubMed1995

Peptide immunoreactivities in the ganglionated plexuses and nerve fibers innervating the human gallbladder.

The mammalian gallbladder is innervated by a well-developed intrinsic neural network. However, little is known about the neurochemistry and organization of the innervation of this organ in humans. The aim of this study was to analyze the distribution of immunoreactivity (IR) for the neuropeptides, vasoactive intestinal polypeptide (VIP), neuropeptide Y (NPY), tachykinins (TK) and calcitonin gene-related peptide (CGRP) in the human gallbladder by means of immunohistochemistry. Neuropeptide-IRs are found in neurons and processes of the two ganglionated plexuses, i.e., the innermost plexus located in the lamina propria at the base of the mucosal folds, and the outermost plexus situated within the fibro-muscular layer. In these two plexuses, VIP-, NPY- and TK-IRs are present in ganglion cells and varicose fibers, whereas CGRP-IR is confined to nerve processes. VIP-IR is present in most, if not all, neurons. NPY- and TK-IRs are also found in many neurons. The densities of the peptide-IR nerves in the mucosa are NPY and VIP > TK >> CGRP, and in the fibro-muscular layer are NPY > VIP and TK > CGRP. The vasculature is richly innervated by NPY-IR nerves, which are mostly perivascular. CGRP-, VIP- and TK-IR processes are found only occasionally around blood vessels and in a paravascular position. Double-label studies demonstrated that a large number of VIP-containing neurons expresses NPY- or TK-IR. On the other hand, all neurons positive for either NPY- or TK-IR are immunostained for VIP. In agreement with these findings, most of the NPY-IR fibers in the lamina propria and fibro-muscular layer contain VIP-IR, and numerous TK-IR fibers are positive for VIP. However, the perivascular NPY-IR processes do not contain VIP-IR, suggesting an extrinsic origin. In addition, a population of TK-IR processes contains CGRP-IR and presumably originates from extrinsic sources, since CGRP/TK-IR intrinsic neurons could not be detected in the gallbladder. Peptide-IRs have a similar distribution in the neck, body and fundus of the gallbladder. No peptide-containing endocrine/paracrine cells are observed in the epithelium. The presence of peptide-IRs in the ganglionated plexuses and the abundance of peptidergic innervation suggest that peptides exert their effects on gallbladder function by acting directly on tissue targets and influencing intrinsic ganglion cells. Furthermore, the co-localization of more than one peptide in the same neuron raises the possibility that peptides are co-released upon stimulation and might interact at the same target.

Gallbladder↗
PubMed1995

Concentrations of 3,4-dihydroxyphenylalanine and catecholamines and metabolites in brain in an anhepatic model of hepatic encephalopathy.

Alterations in the catecholaminergic neurotransmitter systems have been shown to occur in hepatic failure and may contribute to development of hepatic encephalopathy. In the present study we used the rat after complete hepatectomy as a model for study of changes that occur in brain in acute liver failure. We attempted to identify processes in the synthesis, storage, and metabolism of catecholamine neurotransmitters that might be changed during liver failure by measuring levels of, together with those of norepinephrine and dopamine, the precursor (3,4-dihydroxyphenylalanine) and the neuronal metabolites of dopamine and norepinephrine (3,4-dihydroxyphenylacetic acid and 3,4-dihydroxyphenylglycol, respectively) in different regions of brains of control rats and of rats after hepatectomy. We found that in most brain regions of hepatectomized rats there were increases in the concentration of 3,4-dihydroxyphenylalanine or of dopamine but decreases in the concentrations of norepinephrine or of 3,4-dihydroxyphenylglycol. The particulate/supernatant ratios of catecholamines are indices of retention of neurotransmitters in storage sites. These ratios were not different in brain regions between control rats and hepatectomized rats, suggesting that vesicular retention of catecholamines in brain was not impaired after hepatectomy. The data suggest that inhibition of dopamine-beta-hydroxylase might be a characteristic of hepatic failure.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1995

Essential fatty acid deficiency prevents autoimmune diabetes in nonobese diabetic mice through a positive impact on antigen-presenting cells and Th2 lymphocytes.

Protective effects of essential fatty acid deficiency (EFAD) on autoimmunity were shown in rodents. Our goal was to investigate the mechanisms of EFAD effects on autoimmune diabetes in nonobese diabetic (NOD) mice. Weanling female mice were randomized between a control diet group and an EFAD diet group, and the development of diabetes and immune response was determined over a 6-month period. The cumulative incidence of diabetes was significantly reduced in the EFAD group (20 vs 68.75% in the control group; p < 0.01), without affecting the insulitis process. Splenocyte reactivity to phytohemagglutinin and anti-CD3 antibody was significantly increased in EFAD-fed mice (p < 0.01). The EFAD group also exhibited a dramatic increase in baseline (29-fold) and antigen-presenting cell (APC)-stimulated (10-fold) T cell responses in syngeneic mixed leukocyte reaction. These responses were associated with a marked increase in splenocyte interleukin-4 (IL-4) production, a reduction in interferon-gamma production, and a down-regulation of CD45RB isoform expression. Macrophages in the EFAD group exerted a reduced suppressive effect on concanavalin A-induced splenocyte proliferation and were found to release increased amounts of tumor necrosis factor-alpha and IL-1 and reduced amounts of prostaglandin E2. These results clearly demonstrate that EFAD prevents diabetes in NOD mice. The data suggest an enhanced activity of Th2-like cells, as well as an effect on APC activity linked to alteration in eicosanoid metabolism.

Animals↗
PubMed1994

Nitric oxide producing neurons in the monkey and human digestive system.

Nitric oxide has been proposed as an inhibitory transmitter molecule that plays a role in muscle relaxation and vasodilation in the gastrointestinal tract. The present study analyzes the distribution of nitric-oxide-producing neurons in the monkey and human digestive system by means of nicotinamide-adenine-dinucleotide-phosphate-diaphorase histochemistry. This histochemical method is reliable and convenient for the visualization of neuronal nitric-oxide synthase, the enzyme responsible for nitric-oxide generation. In the gastrointestinal tract, nitric-oxide-synthase-related diaphorase activity was present in nerve fibers running throughout the muscular layer (circular > longitudinal) and in numerous ganglion cells and processes in the myenteric plexus of monkeys and humans. Labelled ganglion cells and fibers also were observed in the submucous plexus, although they were much less numerous than those seen in the myenteric plexus. In the submucosa, a few positive fibers were seen around blood vessels. In the mucosa, stained fibers were sparse at the base of the villi and crypts, whereas they were quite abundant in the muscularis mucosae, especially in the small intestine and colon. In the gallbladder (human), labelling was found in ganglion cells and processes of the innermost and outermost ganglionated plexuses. Stained fibers also were distributed to the muscular layer and, less abundantly, to the mucosa and vasculature. Labelled fibers were more abundant in the sphincter of Oddi (human) than in the gallbladder. In the monkey and human pancreas, nicotinamide-adenine-dinucleotide-diaphorase staining was seen mainly in ganglion cells and fibers of intrapancreatic ganglia, and in processes running among acini, around ducts and in the stroma. A moderate density of stained fibers also was distributed to the vasculature, whereas the islets showed few positive processes. Finally, double label experiments performed in the pancreas showed that the vast majority of neurons producing nitric oxide are immunoreactive for vasoactive intestinal peptide.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Brain regions where cholecystokinin exerts its effect on satiety.

The neuropeptide cholecystokinin (CCK), which is localized within the hypothalamus in integrative centers of feeding regulation, can suppress feeding behavior when exogenously applied into the lateral hypothalamus. Moreover, the endogenous peptide can be released from the same brain locus by stimuli that physiologically are associated with satiety (i.e., gastric meal loads). This endogenously released CCK contributes to the inhibition of feeding behavior during meal intake. These data strongly suggest that hypothalamic CCK may play a physiological role in the termination of feeding behavior. The presence of additional sites sensitive to CCK in extrahypothalamic regions (e.g., medial pons and lateral medulla) argue that the CCK receptor systems may functionally (1) have several links in a linear chain or (2) exist as several parallel systems. The relevance of these extrahypothalamic loci for feeding regulation will require further studies which need to be directed towards the physiological role of the endogenously released CCK in these particular areas, by use of selective CCK antagonists.

Animals↗
PubMed1994

Evidence for uptake of vital dye by activated rat peritoneal mast cells: an in vitro imaging study.

Uptake of material from surrounding medium by activated rat peritoneal mast cells (PMCs) was studied using in vitro peritoneal eluate cells, the vital fluorescent dye sulforhodamine B (SFRM-B), secretagogue compound 48/80, and an imaging technique. PMCs, which undergo different states of degranulation, are shown to possess the ability to take up (by endocytosis) SFRM-B in an activity-dependent manner. The endocytosed dye is incorporated in the granules and can be discharged into the medium when the cells are reactivated. Both the uptake and the discharge processes are calcium-dependent. The reactivity of mast cells to secretagogue is not altered by the application of the dye. SFRM-B, a negatively charged, nonspecific protein stain, displays greater photostability and less leakage than the positively charged acridine orange, and its fluorescence persists for hours, whereas acridine orange fluorescence fades within 1 min when exposed to ultraviolet illumination. The fluorescent image of the dye-loaded mast cells can be preserved overnight in a container at room temperature. SFRM-B elicits no detectable damaging influence on the activated afferent discharge of splanchnic afferent nerve fibers with mesenteric terminals. This enables the use of SFRM-B for studying the interactions between mesenteric afferent terminals and their surrounding mast cells.

Afferent Pathways↗
PubMed1994

Regulation of polyunsaturated fatty acid-stimulated insulin release by GIP in isolated perifused islets.

It has recently been suggested that gastric inhibitory polypeptide (GIP) may block the risk factors associated with both hypo- and hyperglycemia by either suppressing or enhancing (depending on the prevailing glucose conditions) insulin release. In the present study we examined, through the use of isolated perifused murine islets, the effect of GIP on insulin secretion that was stimulated by polyunsaturated fatty acids (PUFA) in the presence of low or high glucose concentrations. For each experiment, islets were preperifused at the rate of 1 ml/min for 1 h at 37 degrees C with Krebs-Ringer bicarbonate buffer pH 7.4 that was continuously gassed with 95%/5%, O2CO2, and which contained 5.5 mM (basal) glucose, 2% bovine albumin, and 100 kIU/ml trasylol. Basal samples were then taken before PUFA were added to the perifusate of 5.5 or 27.7 mM glucose, in the absence (control) or presence of synthetic human GIP, and in 20-min perifusion cycles. Solutions were changed using a stopcock, and effluent samples collected on ice were stored frozen until radioimmunoassay for insulin. The addition of a mixture of 10 mM linoleic acid (18:2, omega 6) and 5 mM linolenic acid (18:3, omega 3), to basal glucose perifusate stimulated insulin secretion from a mean basal rate of 61 +/- 2 to 220 +/- 21 pg/islet/min (p < 0.001, n = 5). When GIP concentrations of either 1 x 10(-9) or 1 x 10(-8) M were added to the fatty acid perifusate, insulin secretion stimulated by PUFA was significantly attenuated in a dose-dependent manner, but was completely restored after withdrawal of GIP.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Pancreatic cancer.

Explore the source record for details and available documents.

Biomarkers, Tumor↗
PubMed1993

Enteroendocrine peptides in a canine model of orthotopic jejunoileal autotransplantation.

The enteroendocrine cells of the small bowel provide a rich source of regulatory peptides involved in the modulation of gastrointestinal function. Recent work from our laboratory showed that in situ neural isolation (autotransplantation) of the jejunoileum produced marked changes in tissue expression of several neuropeptides. In the present study, we examined the influence of extrinsic innervation on the tissue expression of endocrine peptides localized to various regions of the gastrointestinal tract. Concentrations of immunoreactive gastric inhibitory polypeptide (GIP), neurotensin (NT) and peptide tyrosine tyrosine (PYY) in fasting plasma and regional tissue biopsies were determined before and at varying time points (2, 6, 12 weeks) after a model of canine orthotopic jejunoileal autotransplantation. GIP was not altered in plasma or tissue at any time point. Plasma concentrations of NT and PYY increased after autotransplantation. Following a decrease in tissue concentrations two weeks after autotransplantation, NT increased progressively from 2 to 6 to 12 weeks, reaching a maximal increase of 895% over baseline in proximal ileum. Tissue concentrations of PYY followed much the same pattern as NT, but these trends never achieved statistical significance. Chromatographic characterization of tissue biopsy extracts revealed molecular heterogeneity of NT-like immunoreactivity, while GIP and PYY immunoreactivity coeluted as single species with authentic standards. Taken together with our earlier observations, it appears that disruption of extrinsic and intrinsic neural continuity to the jejunoileum (autotransplantation) does not affect gut endocrine peptides such as GIP and PYY to the same extent as enteric neuropeptides. NT has been localized to neural as well as endocrine cells and is involved in the temporal adaptive response to autotransplantation.

Animals↗
PubMed1993

Characterization of neuropeptides extracted from canine intestine.

Quantitative determination of neuropeptides in biologic tissues by radioimmunoassay requires both an efficient extraction of neuropeptides as well as maintenance of immunochemical reactivity. Vasoactive intestinal peptide, substance P, and met5-enkephalin were chosen for this study because they are neuropeptides which appear to be involved in multiple physiologic systems. Since all three neuropeptides have a methionine residue within their amino acid sequence, oxidation of methionine to methionine-sulfoxide during the extraction process could diminish their immunochemical reactivity. Multiple factors that might be important in extracting these neuropeptides from canine intestine, including pH of the solvent, tissue homogenization, heating, and addition of enzyme inhibitors, were examined. Concentrations of vasoactive intestinal peptide-like immunoreactivity and substance P-like immunoreactivity were significantly higher in acidic solvents, and tissue homogenization appeared to increase the concentrations of these two neuropeptides. Substance P-like immunoreactivity was increased by heating after tissue homogenization, suggesting heat-induced denaturation of tissue enzymes liberated by homogenization. Separation of acidic tissue extracts by high performance liquid chromatography followed by radioimmunoassay for all three neuropeptides revealed minor acid-induced oxidation of substance P. These results should be useful for planning the extraction of these three neuropeptides from other tissues.

Acetates↗
PubMed1993

Dual effects of gastric inhibitory polypeptide on insulin secretion.

The role of gastric inhibitory polypeptide (GIP) on insulin secretion in the presence of different glucose concentrations has been studied in perifused microdissected murine islets. Insulin secretion was concentration dependent in the presence of glucose alone: Switching the perifusion buffer from 5.5 to 11.1 and 22.2 mM glucose caused an increase in insulin response assessed as the total integrated area under the curve over a 20-min period (6.4 +/- 0.48 and 12.1 +/- 0.58 ng, respectively; p < 0.01, n = 6). If 11.1 mM glucose perifusion in the presence of GIP was preceded by 5.5 mM glucose alone, the integrated insulin secretion/20 min above basal level was attenuated (1.46 +/- 0.10 vs. 0.37 +/- 0.03 ng; p < 0.01, n = 6), and withdrawal of GIP from the perifusion buffer resulted in the restoration of 11.1 mM glucose-stimulated insulin secretion (1.46 +/- 0.10 vs. 1.98 +/- 0.12 ng). If islets were continuously perifused with 11.1 mM glucose, the addition of GIP did not alter insulin secretion. In contrast, the addition of GIP to 22.2 mM glucose perifusion buffer further enhanced the high glucose-induced insulin secretion above basal (12.1 +/- 0.58 vs. 14.5 +/- 0.84 ng; p < 0.05, n = 6). These observations are consistent with a hypothesis that during a low glucose condition, GIP prevents the risk of hypoglycemia by suppressing insulin secretion, while during a high glucose load, glucose-induced insulin stimulation is potentiated by GIP, presumably to prevent hyperglycemia.

Animals↗
PubMed1993

Cholinergic regulation of phase II interdigestive pancreatic secretion in humans.

Small fluctuations in cholinergic input may be involved in the regulation of human interdigestive pancreatic secretion. To determine the effects of small changes in cholinergic tone on phase II interdigestive trypsin secretion, we gave cholinergic agonists or antagonists to 17 healthy fasting subjects who underwent gastrointestinal intubation. Duodenal trypsin outputs, gastroduodenal motility, and plasma levels of pancreatic polypeptide (PP) as a marker of cholinergic tone were measured during intravenous infusion of bethanechol (0, 5, or 40 micrograms.kg-1.h-1) or atropine (0, 4, or 16 micrograms.kg-1.h-1) given during phase II alone or in combination based on a 3 x 3 factorial design. Data were evaluated by a response surface analysis of the average log values for the test period (using the average of log values of the control period as a covariate). Bethanechol increased trypsin output (p < 0.05) and plasma concentrations of PP (p < 0.05) within the ranges of spontaneous fluctuations of trypsin output and PP during phase II, but did not disrupt the periodicity of pancreatic secretion or the characteristic cyclical pattern of interdigestive motility and induction of phase III activity. Atropine markedly decreased trypsin output (p < 0.05) and plasma concentrations of PP (p < 0.05) and abolished the cycling of interdigestive pancreatic secretion and motor activity. These data suggest the hypothesis that cholinergic pathways participate in the control of interdigestive pancreatic secretion during phase II, while enzyme secretion during phase III may be regulated by other mechanisms.

Acetylcholine↗