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Biomedical subjects

V L Go

Publications and source records attributed to V L Go.

At least 163 records · Page 9Linked to original sources
PubMed1983

In vivo studies on the basal and evoked release of cholecystokinin and vasoactive intestinal polypeptide from cat cerebral cortex and periventricular structures.

In cat, radioimmunoassay revealed high concentrations of vasoactive intestinal polypeptide (VIP) and cholecystokinin (CCK) (approximately 10-90 ng/g wet weight tissue) in various regions of the cerebral cortex and in periventricular structures. Superfusion of cat cerebral cortex or perfusion from the lateral ventricle to the cisterna magna with artificial cerebrospinal fluid (CSF) was carried out in cats anesthetized with chloralose-urethane. The superfusate was assayed for VIP- and CCK-like immunoreactivity (VIP-LI and CCK-LI) simultaneously. Basal efflux of VIP-LI was 13.8 +/- 4.1 fmol/30 min/cm2 cortex and 31.6 +/- 5.0 fmol/30 min in ventriculo-cisternal superfusate. Basal efflux of CCK-LI, assayed in the same superfusate sample, was 10.7 +/- 2.5 fmol/30/min/cm2 cortex in cortical cup superfusate and 25.6 +/- 4.4 fmol/30 min in ventriculo-cisternal superfusate. The addition of potassium (50 mM) and veratridine (7.5 X 10(-5) M) to the superfusate produced significant increases in the levels of VIP-LI in both ventricular and cortical effluents. The potassium evoked release of VIP-LI and CCK-LI was inhibited by the substitution of cobalt (4 mM) for the calcium ion in the perfusion media; basal efflux was not affected. Separation of immunoreactivity by gel filtration chromatography demonstrated the CCK-LI in cat cortical tissue co-chromatographed with the COOH-terminal 4, 8, 33 and 39 amino acid peptide fragments of CCK and with a larger molecule. In contrast, the immunoreactivity in cortical and ventricular superfusate obtained during basal and evoked release co-migrated with authentic CCK octapeptide. For VIP, all immunoreactivity in tissue extract of cerebral cortex existed as a single peak which co-migrated with authentic VIP-28. The molecular pattern in cortical superfusate corresponded to that found in tissue extract.

Animals↗
PubMed1983

Assessment of weight loss, food intake, fat metabolism, malabsorption, and treatment of pancreatic insufficiency in pancreatic cancer.

In 12 patients with biopsy-proven pancreatic ductal adenocarcinoma, the following were determined: (1) whether decreased food intake, malabsorption, or altered fat metabolism were associated with weight loss; (2) the effect of pancreatic extract as treatment for malabsorption; and (3) the accuracy of the triolein breath test for detection of steatorrhea. Weight loss occurred in 11 patients and only in patients who had either malabsorption (n = 5), low coefficients of caloric consumption (n = 2), or both (n = 4). Nine patients had fat malabsorption, six had protein malabsorption, and caloric consumption was decreased in seven patients. Metabolism of oleic acid was significantly decreased (P less than 0.01) compared to normal subjects and correlated with basal metabolic rates (r = 0.6; P less than 0.05) which were within the range of normal values for age and sex. Body weight loss correlated only with coefficients of fat and protein absorption (r = 0.59; P less than 0.05). Treatment of patients with pancreatic extract resulted in significant improvement in absorption in those with moderate to severe fat or protein malabsorption (coefficient of absorption less than 80%) but no significant improvement occurred in patients with mild fat or protein malabsorption. The triolein breath test was abnormal in all patients with fat malabsorption and predicted improvement of fat absorption in five of six patients with steatorrhea who were treated with pancreatic extract. Thus, in pancreatic cancer, weight loss is associated with malabsorption; exogenous pancreatic extract significantly improves moderate to severe fat or protein malabsorption, and the triolein breath test detects fat malabsorption and predicts the treatment response to pancreatic extract.

Adult↗
PubMed1983

Concurrent measurement of substance P and serotonin in spinal superfusates: failure of capsaicin and p-chloroamphetamine to co-release.

This study examined the efflux of endogenous serotonin and substance P-like immunoreactive material into in vivo superfusates of the rat spinal cord under quiescent conditions and during the addition of either capsaicin or p-chloroamphetamine to the superfusate. Using a method which permitted concurrent measurement of serotonin and substance P-like immunoreactive material in the same sample of superfusate, it was found that capsaicin increased the efflux of substance P-like immunoreactive material from the spinal cord but did not alter the efflux of serotonin. Conversely, the addition of p-chloroamphetamine caused the efflux of serotonin from the spinal cord to increase, but did not affect the efflux of substance P-like immunoreactive material.

Amphetamines↗
PubMed1983

Effects of size, time of day and sequence of meal ingestion on carbohydrate tolerance in normal subjects.

The effects of size, time of day and sequence of meal ingestion were determined in healthy subjects using a Latin square design. Plasma glucose, insulin and gastric inhibitory polypeptide, but not glucagon, were correlated with meal size. Plasma glucose, but not insulin, gastric inhibitory polypeptide or glucagon, were greater later in the day. The progressive decline in carbohydrate tolerance from 08.00 to 18.00 h was associated with impaired insulin secretion estimated by C-peptide, and with impaired insulin action.

Adult↗
PubMed1983

Motilin regulation of canine interdigestive intestinal motility.

The objective was to determine whether motilin regulates cyclical interdigestive motility in the jejunum as well as in the duodenum. In four conscious dogs with an intact innervated duodenum, an autotransplanted (extrinsically denervated) 75-cm loop of proximal jejunum, and an autotransplanted, in situ distal jejunum, interdigestive myoelectrical complexes cycled independently in all three regions of small bowel. Plasma concentration of motilin was greater during phase III of the duodenal cycles (304 +/- 37 pg/ml) than during phase I (235 +/- 37 pg/ml) or phase II (235 +/- 39 pg/ml; P less than 0.05), but the concentration did not vary consistently with the phases of the cycles in the autotransplanted jejunal segments. Intravenous infusions of motilin (0.6 microgram/kg/min for 5 hr), begun 15-30 min after passage of phase III through the duodenum, shortened the interval between phase IIIs in the duodenum from 147 +/- 14 min before infusions to 44 +/- 3 min during the infusions (P less than 0.05), but did not alter consistently the interval between phase IIIs in the autotransplanted jejunal segments. Feeding decreased plasma motilin concentration. The data were consistent with motilin regulation of interdigestive motility in intact, innervated canine duodenum but not in extrinsically denervated jejunum.

Action Potentials↗
PubMed1983

Not 'indifference to pain' but varieties of hereditary sensory and autonomic neuropathy.

Three children, from different kinships, with generalized insensitivity to pain, showed unusual manifestations of congenital, presumably inherited, sensory and autonomic neuropathy. The first child appeared to have a syndrome resembling those previously described as congenital indifference to pain, congenital universal loss of pain sensation from infancy without other apparent neurological deficit. Unlike most types of hereditary sensory and autonomic neuropathies (types I, II, III), but like type IV, she had normal sensory nerve action potentials. Abnormalities of sudomotor function and of somatosensory evoked potentials were demonstrated. A severe decrease in the number of sural nerve A delta fibres and a small reduction in C fibres were demonstrated morphometrically. An abnormality of C fibres was confirmed by a marked reduction in nerve dopamine-beta-hydroxylase activity. The plasma and CSF concentrations of beta endorphins, substance P and several other neuropeptides and hormones were normal. Unequivocal evidence of a neuropathic lesion is provided by this patient; her disorder may be identified as the fifth type of hereditary sensory and autonomic neuropathy. The second patient had a congenital pansensory neuropathy and progressive retinitis pigmentosa. Whether the disorder is inherited and, if so, whether the retinitis pigmentosa results from the same or from a second genetic abnormality, is unclear. The third case has, in addition to what is usually seen in hereditary sensory and autonomic neuropathy, type II, an unusually severe kinaesthetic difficulty in oral food handling. The sural nerves of the second and third patients had fibre composition characteristic of hereditary sensory and autonomic neuropathy, type II, few or no myelinated fibres and reduced numbers of unmyelinated fibres.

Autonomic Nervous System Diseases↗
PubMed1983

Enhancing the anti-dumping effect of Roux gastrojejunostomy with intestinal pacing.

We wondered whether Roux gastrojejunostomy alone or with intestinal pacing would slow gastric emptying and ameliorate the dumping syndrome after truncal vagotomy and subtotal distal gastrectomy. In five conscious dogs with vagotomy and distal gastrectomy, the Roux loop alone slowed gastric emptying of 100 ml 5% glucose instillates, but not of 100 ml 25% glucose instillates, while pacing the loop backwards slowed emptying of both. Pacing also decreased the postcibal hemoconcentration and hyperglycemia found after the 25% instillates. However, pacing did not alter the postprandial hyper-GIP-emia (gastric inhibitory peptide) and hyperinsulinemia found in Roux gastrectomy dogs, suggesting that pacing worked by slowing emptying of glucose rather than by releasing enteric hormones. Although pacing did not stimulate jejunal action potentials (contractions), the greater the number of action potentials occurring during pacing, the more the slowing (r = .738, p less than .001). We concluded that the combination of Roux gastrojejunostomy and pacing ameliorated postgastrectomy dumping in dogs. The tests provide a basis for treating humans with postgastrectomy dumping.

Animals↗
PubMed1983

Collaborative study for the evaluation of multiple simultaneous markers in lung cancer.

The search for tumor markers suitable for use in diagnosis and management of patients with lung cancer has met with limited success because each available marker lacks sufficient sensitivity and specificity. We have begun a collaborative study to evaluate multiple simultaneous serum markers to determine whether there is a combination that will increase both sensitivity and specificity to the degree that noninvasive serologic tests might provide a means for managing patients with lung cancer. The National Cancer Institute, Bethesda, Maryland, has established a Serum Bank which can supply identical aliquots of the same serum sample to several different laboratories to perform quantitative assays for a number of markers. The results of these assays will serve as a data base to be analyzed for selection of the optimal grouping of markers for the different types of lung cancer and for evaluation of different biostatistical techniques to maximize the benefit derived by multiple marker determination. The evaluation of multiple markers will be carried out in several separate steps: (a) determination of a combination of markers that discriminate advanced lung cancer from benign lung disease; (b) demonstration of the ability of that combination to define early or localized lung cancer; (c) selection of a combination that best separates lung cancer from cancer of other sites; (d) testing of combined markers for the ability to predict response to therapy, including detection of early recurrence before clinical signs appear; and (e) evaluation of the combination(s) for effectiveness in detecting lung cancer in asymptomatic individuals. The experimental design and selection of markers will be presented and discussed.

Adenocarcinoma↗
PubMed1983

Vasoactive intestinal polypeptide: a putative transmitter in the canine gastric muscularis mucosa.

The nature of the inhibitory transmitter in the canine gastric muscularis mucosae was studied in vitro using superfusion techniques. The inhibitory effect of nerve stimulation (10 V, 200 mus, 10 Hz) was not altered by adrenergic, cholinergic or serotonergic antagonists. Adenosine triphosphate had no effect on spontaneous mechanical activity. Nucleotide pyrophosphatase and apamin had no effect on the response to nerve stimulation. Alpha-chymotrypsin abolished the inhibitory effect of nerve stimulation. Radioimmunoassay of the muscle indicated the presence of gastrin/cholecystokinin-substance P- and vasoactive intestinal polypeptide (VIP)-like immunoreactivity. Of the three peptides present, only VIP produced a concentration-dependent relaxation. A substance with VIP-like immunoreactivity was released during nerve-induced relaxation of the muscle, and its release was blocked by tetrodotoxin and calcium-depleted solution. The inhibitory effect of nerve stimulation was abolished by VIP antiserum. These data strongly support the hypothesis that VIP or a closely related peptide is an inhibitory neurotransmitter in the canine gastric muscularis mucosae.

Animals↗
PubMed1983

Effect of graded intraduodenal glucose infusions on the release and physiological action of gastric inhibitory polypeptide.

Gastric inhibitory polypeptide (GIP) is the leading candidate for gut hormonal augmentation of insulin release. The release of its subspecies (mol wt, 5000 and 7500) and the physiological action of total immunoreactive GIP (IR-GIP) were investigated during isotonic glucose infusions at 75, 225, and 465 mg/min in nine volunteers. Each dose was infused intraduodenally and iv in the same volunteer. Intestinal augmentation of insulin release occurred during the high dose intraduodenal glucose infusion (P less than 0.001) but not during the lower doses. An elevation of 17-20 mg/dl in plasma glucose was required before this insulinotropic effect occurred (P less than 0.001). At increments of plasma glucose above 17 mg/dl, the augmentation of gut-mediated insulin release was dependent on the degree of hyperglycemia (r = 0.81; P less than 0.01). At each dose of intraduodenally administered glucose, IR-GIP was elevated within 20-40 min (P less than 0.01), remaining at a steady level until the infusion was stopped. The release of IR-GIP was elevated within 20-40 min (P less than 0.01), remaining at a steady level until the infusion was stopped. The release of IR-GIP was proportional to the intestinal glucose load but was unchanged from the basal level during iv glucose studies. The attained IR-GIP levels remained constant in each study despite large variations over time in plasma glucose and insulin concentrations. During intestinal glucose infusion, 58.7 +/- 4.1% of IR-GIP was accounted for by the 5000 mol wt subspecies and 17.3 +/- 3.5% was accounted for by the 7500 mol wt subspecies, with the remaining immunoreactivity found in the void volume of a Sephadex G-50 column. Relative proportions remained constant throughout the 4-h study. Thus, during glucose stimulation, the total IR-GIP released 1) is proportional to the absorbable luminal stimulus, 2) is independent of ambient plasma insulin and glucose levels, 3) is composed predominantly of the 5000 mol wt form, and 4) requires an elevation in plasma glucose of 17-20 mg/dl before it augments insulin release, but then stimulates insulin release in a fashion linearly dependent upon the increment in plasma glucose.

Adult↗
PubMed1983

The syndrome of gastric argyrophil carcinoid tumors and nonantral gastric atrophy.

Records of the 30 cases of gastric carcinoid at the Mayo Clinic showed that the gastric mucosa was normal, hyperplastic, or atrophic (nonantral) in 12, 2, or 16 patients, respectively. In the atrophic group, the tumors were in the gastric body and fundus; small, polypoid, and multicentric; and associated with fundal argyrophil cell hyperplasia. In immunocytochemical studies, minor tumor cell populations stained positively for 5-hydroxytryptamine, gastrin, and somatostatin in 1 case and for 5-hydroxytryptamine in 3 others. Metastasis occurred in 3 patients. Twelve patients had pernicious anemia. Parietal cell or intrinsic factor antibodies or both were present in all 12 patients tested. Each of the 7 patients with an intact antrum had massive hypergastrinemia. No common HLA-A, -B, or -DR antigen pattern was detected among the 10 patients tested. The results suggest that nonantral gastric atrophy predisposes to gastric carcinoid as well as to gastric carcinoma.

Adult↗
PubMed1983

Short-term inhibition of duodenal tryptic activity does not affect human pancreatic, biliary, or gastric function.

Existence of feedback inhibition of pancreatic secretion by luminal pancreatic trypsin in humans is controversial. We examined the effect of duodenal tryptic activity on pancreatic, biliary, and gastric functions. In six healthy volunteers, gastric acid secretion and emptying and the secretion of pancreatic enzymes, bicarbonate, and bile acids into the duodenum were measured for 7 hr with a double-marker perfusion technique. Each experiment consisted of six test periods. The effects of the addition of active and inactive aprotinin to duodenal saline perfusion were determined during fasting and after administration of a saline test meal. We found that (1) aprotinin eliminated tryptic activity in the preprandial state and reduced it by more than 95% during meal periods; (2) compared to inactivated aprotinin, no differences in the outputs of bicarbonate, amylase, lipase, chymotrypsin, and bile acids occurred during preprandial or postprandial aprotinin periods; and (3) gastric acid secretion, emptying, and duodenogastric reflux were similar during aprotinin and inactivated-aprotinin perfusions. We conclude that short-term, almost complete reduction of intraduodenal tryptic activity does not alter exocrine pancreatic secretion or gastric function in the unstimulated state or in response to a moderate stimulation by a saline test meal. Therefore the importance of negative feedback control of pancreatic secretion by acute alteration of intraduodenal tryptic activity must be questioned in healthy humans.

Adult↗
PubMed1983

A soluble interaction between dibutyryl cyclic guanosine 3':5'-monophosphate and cholecystokinin: a possible mechanism for the inhibition of cholecystokinin activity.

N2,O2'-dibutyryl cyclic guanosine 3':5'-monophosphate has been reported to inhibit the activity of cholecystokinin on several different end organ responses and in several species. Although the mechanism of this inhibition is unclear, competitive antagonism at the level of the receptor has been suggested. We have investigated an alternate possibility, that N2,O2'-dibutyryl cyclic guanosine 3':5'-monophosphate inhibits cholecystokinin action by interacting directly with the peptide while both are in solution. We used antisera with specificities for different regions of cholecystokinin-gastrin peptides and radioiodinated cholecystokinin-33, cholecystokinin-8, and gastrin-17. Our results support the possibility of a soluble interaction between N2,O2'-dibutyryl cyclic guanosine 3':5'-monophosphate and the peptides of cholecystokinin-gastrin family that is specific for the COOH-terminal (receptor binding) region of these peptides, that is dependent on the concentration of N2,O2'-dibutyryl cyclic guanosine 3':5'-monophosphate, and that correlates with concentrations that inhibit biologic activity. The proposed N2,O2'-dibutyryl cyclic guanosine 3':5'-monophosphate-cholecystokinin complex is dispersed by gel filtration chromatography, and is prevented from being formed by certain detergents.

Antigen-Antibody Reactions↗
PubMed1983

Stress-induced gastroduodenal motor disturbances in humans: possible humoral mechanisms.

The objectives of this study were threefold. First, we investigated the effects of acute stressful stimuli on gastroduodenal feeding activity after a physiologic meal. Second, we explored the possible role of humoral mediators of these effects by measuring concurrently plasma levels of beta-endorphin, catecholamines, and several gut peptides. Third, we wished to determine whether or not the gut responded selectively to different types of central stimuli. Thus, in 12 healthy volunteers we studied the effects of vertigo and cold pain on the gastrointestinal motor response to a solid meal. Pressure activity was recorded by a low-compliance perfusion system. Plasma concentrations of beta-endorphin and gut peptides were measured by radioimmunoassay, whereas catecholamine levels were measured by high-pressure liquid chromatography. Blood pressure, pulse rate, and skin conductance were also monitored. Labyrinthine vertigo (by otic stimulation with 10 degrees C water; control, 37 degrees C water) and cold pain (immersing hand in 4 degrees C water; control, 37 degrees C water) were simultaneously induced after the meal in each subject according to a 2 X 2 factorial experimental design. Cold pain and labyrinthine stimulation alone or in combination significantly reduced the antral phasic pressure response to solids while elevating plasma levels of beta-endorphin and norepinephrine. These effects occurred within the first 20 min poststimulus and were associated with changes in blood pressure, pulse rate, and skin conductance. Further, in 2 of 6 individuals in whom vertigo was induced by labyrinthine stimulation, a phase 3-like burst of motor activity appeared in the duodenum and migrated aborally. We conclude that centrally acting external stimuli may severely disrupt antral feeding activity. Furthermore, concurrent elevations in plasma levels of beta-endorphin and norepinephrine raise the possibility that these substances may be involved as mediators of the central effects on the gut.

Adult↗
PubMed1983

The role of gastrointestinal hormones in the control of postprandial and interdigestive gastrointestinal function.

Gastric, pancreatic, biliary, and intestinal functions during interdigestive and postprandial periods can now be quantified and correlated with changes in gastrointestinal hormone concentrations. Through this type of study, we can begin to glimpse the physiological roles of gastrointestinal hormones. The segments of the gastrointestinal tract which regulate each digestive function can be determined by experimental manipulations in which postprandial chyme is diverted from or exposed to particular areas of the bowel through the use of occlusive balloons. These studies suggest that the upper gut is capable of regulating biliary and pancreatic function, while the stomach and the entire small bowel affect stomach function. In addition, gastric secretion is regulated more proximally than gastric emptying. Knowledge of the hormones present in different segments of the bowel permits hypothesis of their physiological regulatory functions.

Bicarbonates↗
PubMed1983

Serum bank for biological markers for breast cancer.

A bank of serum specimens from women at varying risks of breast cancer has been established. Panels of test specimens can be secured by qualified investigators to evaluate newly discovered biological markers for breast cancer, to verify preliminary data, and to compare performance of established assays among different laboratories. Panels consisting of coded 1-ml vials of sera will be sent upon request to approved investigators. The procedure for application for serum panels is described.

Blood Banks↗
PubMed1983

Medical and surgical options in the management of patients with gastrinoma.

We reexamined our experience with the surgical and medical management of 53 patients with Zollinger-Ellison syndrome due to gastrinoma during the past decade. Surgical "cure" (defined here as resection of all identifiable tumor with normalization of serum gastrin and gastric secretory variables) appeared possible in 7 patients (of 44 explored, or 16%). Five of the 7 "cured" patients had duodenal wall tumors. Currently, these 7 receive no therapy, and none has apparent metastasis or multiple endocrine neoplasia, type 1. Excluding patients who have metastasis or multiple endocrine neoplasia, type 1 by preoperative screening would have increased the relative chance of surgical "cure" from 16% to 20% (7 of 35). Patients with unresectable or recurrent gastrinomas had a much worse prognosis than did patients whose tumors did not recur after resection or patients with a negative laparotomy. In any case, therapy with H2-receptor antagonists offered a satisfactory fallback position for management of gastric hypersecretion and its consequences. Adequate control by their use was achieved in 16 of 18 patients who were followed up an average of 28.9 mo (range 7-59 mo) without major side effects. Total gastrectomy, while undoubtedly the most effective therapy of gastric hypersecretion, is not free of significant sequelae, as evidenced by long-term follow-up of 18 gastrectomized patients. We concluded that (a) patients with Zollinger-Ellison syndrome without multiple endocrine neoplasia, type 1 or metastasis should undergo exploratory laparotomy and potential resection of identifiable gastrinomas, (b) chronic therapy with H2-receptor antagonists is preferable to total gastrectomy and satisfactory control may be achieved in most patients, and (c) tumor death is currently the major threat to survival for patients with unresectable gastrinomas, particularly nonmultiple endocrine neoplasia, type 1.

Cimetidine↗