Biomedical subjects

V L Go

Publications and source records attributed to V L Go.

At least 73 records · Page 4Linked to original sources

PubMed1990

Sites in the brain at which cholecystokinin octapeptide (CCK-8) acts to suppress feeding in rats: a mapping study.

In this study, an examination was made of the sites in the brain of the rat at which the injection of cholecystokinin octapeptide (CCK-8) would alter food intake. Rats fasted for 24 hr received intracerebral injections of CCK-8 (1 nmol) or an equal volume of saline (0.5 microliters), into various sites in the brain through permanently implanted stainless steel cannulae. After prior acclimatisation to individual plexiglass compartments, latency to feed, as well as consumption of food and water during 0-20, 20-40 and 40-60 min after the injection, were recorded. The available food was the standard rat pellets, to which the animal otherwise had constant daily access. With this paradigm, active sites at which CCK-8 suppressed feeding were defined as sites at which consumption of food for 0-20 min was reduced by 25% or more, or the latency to feed was increased by 3 min or more after the injection of CCK-8, as compared to the effect of the injection of saline, made at the same site. Such active sites were most densely distributed in the rostral diencephalon, e.g. hypothalamus, the medial pontine area and lateral medulla, in the vicinity of the nucleus tractus solitarii (NTS). By grouping data for injections according to histologically identified sites, statistical analysis of groups of injections confirmed that these three major areas of the brain were active with regard to the suppression of feeding by CCK-8. These data suggest that CCK may not only initiate satiety messages, as a circulating hormone at peripheral sites, but also participate in the conduction of such information to the target in the brain by serving as a neurotransmitter in the lateral medulla (e.g. NTS), medial pontine area (e.g. relay station between the NTS and hypothalamus) and the lateral hypothalamus, where local release of CCK-8 after stomach loading has been observed.

Animals↗

PubMed1990

Postpartum changes in pattern of gastrointestinal regulatory peptides in human milk.

Concentrations of gastrointestinal neuropeptides in serial human milk samples from 28 women were determined over the first 6 postpartum mo. All gut neuropeptides were present during the first postpartum week. Gastric inhibitory peptide (GIP) concentration remained constant but the others decreased by 6 wk. Bombesin concentration in breast milk was threefold greater than concurrent plasma concentration (p less than 0.001); all other neuropeptides were at the same or lower concentrations in milk than in plasma. At 36 wk gestation plasma concentrations of GIP were lower and concentrations of vasoactive intestinal peptide were higher than concentrations in age-matched control subjects. Concentrations of gastrin and cholecystokinin, bombesin, peptide histidine methionine, peptide YY, and neurotensin in plasma were similar in pregnant and nonpregnant women. These gut neuropeptides in milk may be important for growth and maturation of the gastrointestinal system in neonates. Bombesin may contribute to neonatal hypergastrinemia.

Adult↗

PubMed1990

Lack of effect of gastric inhibitory polypeptide on hepatic and extrahepatic insulin action.

To assess the influence of enteric factors on insulin action, seven lean healthy subjects were studied under conditions of hyperinsulinemic euglycemic glucose clamp, double isotope administration, and enteral vs. parenteral glucose infusion. In random order, glucose and mannitol radiolabeled with [2-3H]glucose were infused intraduodenally for 4 h while the systemic rate of glucose turnover was assessed by [6-14C]glucose. During the final hour of the study, plasma glucose, insulin, C-peptide, glucagon, cholecystokinin, and neurotensin were similar under both experimental conditions. Despite an increase in gastric inhibitory polypeptide concentration during combined enteral and iv glucose infusion to levels that mimicked meal ingestion, total glucose infusion rate, insulin-induced stimulation of glucose uptake, and insulin-induced suppression of hepatic glucose release were comparable to those observed during iv glucose administration. These data indicate that under conditions of modest hyperinsulinemia and euglycemia, gastric inhibitory polypeptide did not influence hepatic or extrahepatic insulin action.

Adult↗

PubMed1989

NIH conference. Somatostatin and somatostatin analogue (SMS 201-995) in treatment of hormone-secreting tumors of the pituitary and gastrointestinal tract and non-neoplastic diseases of the gut.

Somatostatin is a peptide synthesized in many tissues that can act as a neurotransmitter, a systemic hormone, or a local hormone, and inhibits the secretion of hormones or other cell products. A long-acting synthetic analogue of somatostatin (SMS 201-995) has been developed which when administered subcutaneously has a biologic half-life of 90 to 120 minutes and can be administered 2 or 3 times per day. SMS 201-995 can lower plasma concentrations of growth hormone and somatomedin-C in patients with pituitary acromegaly, but no controlled trials to assess symptomatic response or change in tumor size have been done. In patients with pituitary thyrotropin-producing pituitary tumors, SMS 201-995 has been remarkably effective in producing biochemical and clinical responses and is the drug of first choice in this syndrome when tumor resection is not possible. In patients with the carcinoid syndrome, SMS 201-995 effectively reduces diarrhea, is the best available drug for treatment of carcinoid flush (effective in approximately 90% of cases), and is useful in treating carcinoid crisis. Eighty-five percent of patients with pancreatic islet cell tumors that produce vasoactive intestinal peptide will respond to SMS 201-995 with a reduction in diarrhea that often has been resistant to all other therapy. SMS 201-995 may also be useful in treating the symptoms in some patients with glucagonomas, growth hormone releasing hormone-producing tumors and insulinomas. Whether SMS 201-995 has a significant effect on gut neuroendocrine tumor growth remains uncertain. Certain nonmalignant diseases of the gut respond to somatostatin, including secretory diarrhea and fistulas of unknown cause. In general, SMS 201-995 has proved safe with few significant side effects, but whether the long-term use of the drug will result in an iatrogenic form of the somatostatinoma syndrome is uncertain.

Acromegaly↗

PubMed1989

Extrahepatic malignancy following long-term immunosuppressive therapy of severe hepatitis B surface antigen-negative chronic active hepatitis.

To determine the frequency, predisposing factors and consequences of extrahepatic malignancy following long-term immunosuppressive therapy of severe HBsAg-negative chronic active hepatitis, 149 patients who had received prednisone (20 mg daily) or prednisone (10 mg daily) in combination with azathioprine (50 mg daily) for at least 6 months were evaluated systematically for 109 +/- 5 months (range: 7 to 223 months). Seven neoplasms involving cervix (2), lymphatic tissue (1), breast (1), bladder (1), soft tissue (1) and unknown site (1) developed in seven patients after 116 +/- 23 months (range: 18 to 164 months). The incidence of extrahepatic neoplasm was 1 per 194 patient-years of surveillance, and the probability of tumor occurrence was 3% after 10 years. Tumor frequency was similar in men and women and the risk was 1.4-fold greater than that in an age- and sex-matched normal population (95% confidence interval, 0.6- to 2.9-fold normal). Patients with extrahepatic malignancy were not distinguished by age, sex, treatment regimen, cumulative duration of treatment (42 +/- 9 vs. 60 +/- 4 months, p = 0.7) or individual features of the liver disease. Five of the seven patients survived during 48 +/- 25 months of follow-up, including two patients who have lived for at least 5 years after the diagnosis of malignancy. We conclude that extrahepatic malignancy develops infrequently during long-term immunosuppressive therapy. Its occurrence is not related to the type or duration of treatment, and long-term survival after tumor detection is possible. The low but probably increased risk of extrahepatic neoplasm does not militate against the use of immunosuppressive therapy in these patients.

Azathioprine↗

PubMed1989

A longitudinal survey of self-reported bowel habits in the United States.

Information concerning bowel habits was gathered from a representative sample of 14,407 United States adults in the first National Health and Nutrition Examination Survey in 1971-1975 and approximately 10 years later among the same individuals. The prevalence of self-reported constipation, diarrhea, infrequent defecation (three or fewer bowel movements per week), and frequent defecation (two or more bowel movements per day) increased with aging. Women were more likely than men (P less than 0.05) to report constipation (20.8% compared to 8.0%) and infrequent defecation (9.1% compared to 3.2%). Blacks were more likely than whites to report infrequent defecation (P less than 0.05). Older respondents reporting constipation were more likely to use laxatives or stool softeners than younger respondents reporting constipation, but they were also less likely to have infrequent defecation. To evaluate factors predictive of impaired bowel function, case definitions were created using information concerning complaint of constipation, laxative use, frequency of defecation, and stool consistency. Female gender, black race, fewer years of education, low physical activity, and symptoms of depression were independent risk factors for impaired bowel function. This study provides national estimates of bowel complaints and their natural history and examines possible risk factors for constipation.

Adult↗

PubMed1989

Growth of digestive diseases research funds and investigators supported by the National Institutes of Health.

The object of this paper is to analyze the growth of the digestive diseases research community supported by the National Institutes of Health, based primarily on data from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), during the 10-yr period of fiscal year 1977 through 1986. During that period, research dollars have increased threefold (1.5-fold when corrected for inflation), whereas the number of grants supported by those dollars has increased only 1.5-fold. This increase is similar to that of the entire National Institutes of Health. A greater percentage of grantees now have multiple grants and the cost of multiple grants is greater on a per grant basis. One-half of the funds support the research of only one-fourth of the grantees. The number of competing applications sent to the National Institute of Diabetes and Digestive and Kidney Diseases compared with those sent to the National Institutes of Health shows a smaller increase (26% vs. 40%), whereas more funds are being provided per grant. Ten of the 12 institutes within the National Institutes of Health are now reporting digestive disease research support, so that total support exceeded $200 million in fiscal year 1986. We conclude that the digestive diseases research community is growing very slowly.

Digestive System Diseases↗

PubMed1989

Effect of long-term freezer storage, thawing, and refreezing on selected constituents of serum.

We determined the effect of long-term freezer storage and repeated thawing and freezing of serum on concentrations of electrolytes (sodium, potassium, calcium, and phosphate), enzymes (aspartate aminotransferase, alkaline phosphatase, lactate dehydrogenase, and creatine kinase), total protein, tumor markers (carcinoembryonic antigen and alpha-fetoprotein), and other substances. Vials (1 ml) of frozen serum from a single blood drawing from 40 women with no breast disease and 70 with benign breast disease were analyzed annually from 1983 to 1987. Blood had been obtained from 40 subjects in 1978, 40 in 1980, and 30 in 1983. Thawing and refreezing studies were done in two ways: (1) serum samples from 30 subjects with benign breast disease were thawed at weekly intervals for 6 weeks and (2) serum samples from 30 patients with stage IV breast cancer were analyzed for alpha-fetoprotein and carcinoembryonic antigen, and serum specimens from 23 patients with benign breast disease and 7 control subjects were analyzed for lactate dehydrogenase and creatine kinase after thawing and keeping the samples at room temperature for up to 4 hours and then refreezing them. For measuring laboratory variability, duplicate samples were processed. Long-term storage (up to 10 years) and repeated thawing and refreezing did not affect the results of any tested constituents of serum. Although most measurements showed statistically significant variability over test cycles, these differences were thought to be due to laboratory variability.

Biomarkers, Tumor↗

PubMed1989

Carbohydrate digestion and release of pancreatic polypeptide in health and diabetes mellitus.

The effects of meal volume and luminal digestion of carbohydrates on the release of pancreatic polypeptide (HPP) were investigated in eight healthy subjects and in six patients who had non-insulin dependent diabetes mellitus. On one occasion each subject ingested a placebo with 200 ml water and a starch (50 g) pudding meal (400 ml) 30 minutes later. On another occasion an amylase inhibitor that retards intraluminal starch digestion was given with the water and starch. In normal subjects, water caused a moderate rise in HPP plasma levels (16.9 (10.9) pg/ml; p less than 0.02) and ingestion of starch increased HPP in a double peaked pattern. The mean increments of the peaks were 45.0 (15.2) pg/ml (p less than 0.02) and 41.1 (17.3) pg/ml (p less than 0.05), respectively. In the diabetic subjects, the HPP concentrations did not increase in response to water. After ingestion of starch the diabetics had two peaks of HPP that were similar in magnitude, but the early postprandial peak was delayed significantly compared to normal subjects (37.5 (5.1) min v 23.4 (3.9) min; p less than 0.05). The amylase inhibitor (5 or 10 g) reduced the early postprandial HPP peak by 79% (p less than 0.05) in normal subjects and 4 g of the inhibitor reduced the early HPP peak by 58% (p less than 0.05) in the diabetics. In both groups ingestion of the amylase inhibitor abolished the late HPP peak (p less than 0.05). In conclusion, carbohydrate induced HPP release is dependent on undisturbed intraluminal starch digestion.

Adult↗

PubMed1989

Release of hypothalamic cholecystokinin in cats: effects of nutrient and volume loading.

Systemic cholecystokinin (CCK) suppresses food intake in various species and has therefore been proposed to act as a satiety factor. Because CCK is also present in the hypothalamus and furthermore meets neurotransmitter criteria, the hypothesis was tested whether CCK participates in the transmission of satiety messages at the lateral hypothalamic (LH) level. The results of this study demonstrate that in halothane-anesthetized cats, neurons located in the LH will indeed release CCK-like material after a carbohydrate-protein meal in a time-dependent fashion. This release, as water loads demonstrate, is most likely due to volumetric distension rather than to the nutrient content. The releasable CCK does not originate from peripheral sources, since intravenously infused CCK octapeptide (CCK-8) does not appear in the perfusate. The release occurs only in discrete neurons and is not universal to CCK-releasing systems within the LH, and also, CCK-releasing systems are not present at all locations. The molecular form of CCK in feline hypothalamus is the COOH-terminal octapeptide (CCK-8) as shown by high-performance liquid chromatography. No gastrin-17 is present. CCK-8 is also the predominant form found in meal-induced as well as in KCl-induced CCK released from hypothalamic neurons. These results suggest a correlated role for hypothalamic CCK in the termination of food intake.

Animals↗

PubMed1988

Isolation and primary structure of human peptide YY.

The isolation, primary structure and chemical synthesis of human peptide YY (PYY) are described. The peptide was purified from human colonic extracts using a chemical method which detected the C-terminal tyrosine amide structure of PYY. Human PYY consists of 36 amino acid residues and the complete amino acid sequence is: Tyr-Pro-Ile-Lys-Pro-Glu-Ala-Pro-Gly-Glu- Asp-Ala-Ser-Pro-Glu-Glu-Leu-Asn-Arg-Tyr-Tyr-Ala-Ser-Leu-Arg-His-Tyr-Leu- Asn-Leu-Val-Thr-Arg-Gln-Arg-Tyr-NH2. The differences between the structures of porcine and human PYY are at positions 3 (Ala/Ile replacement) and 18 (Ser/Asn). Synthetic human PYY prepared using a solid-phase synthetic technique was found to be structurally identical to the natural peptide.

Amino Acid Sequence↗

PubMed1988

Chronic intraventricular administration of cholecystokinin octapeptide (CCK-8) suppresses feeding in rats.

Cholecystokinin octapeptide (CCK-8) is known to suppress feeding in sheep, pigs, golden hamsters and rats following acute intracerebroventricular (i.c.v.) injection. In this study, we report the effects of chronically administered i.c.v. CCK-8 on long-term food intake in rats. After baseline food intake was established over a period of 3 days, rats were implanted with Alzet osmotic minipumps, which delivered 1.0 microliter/h. Three groups of animals were prepared which received saline (vehicle) or CCK-8 at 12.25 micrograms/day (low dose) or CCK-8 at 122.5 micrograms/day (high dose). Surgical preparation of the animals with the intraventricular cannula and the osmotic minipump resulted in an initial reduction in food consumption in all groups. In the saline group daily food consumption returned to presurgery values by day 4. Similar results were observed with the low dose of CCK-8. In contrast, in animals receiving the high concentrations of CCK-8, the initial fall in feeding was more prominent and though it rose during the 7-day infusion interval, it remained statistically below control during this period. After termination of the infusion, daily food consumption rose to normal levels during the next 3 days. For comparison, the cumulative difference between daily food consumption over the period of 8 days during infusion and pre-infusion control was 39.9 +/- 10.0 g/24 h in the saline group. In CCK-8-infused animals, food consumption after pump implantation was reduced by an integrated value of 35.5 +/- 5.0 g/24 h at low dose and 117.4 +/- 20.2 g/24 h at high dose.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1988

Decreased colonic peptide histidine-methionine in idiopathic inflammatory bowel diseases.

The sequence for peptide histidine-methionine is present within the same preprohormone as vasoactive intestinal polypeptide. Since our previous study using radioimmunoassay had demonstrated significantly decreased colonic concentrations of vasoactive intestinal polypeptide in ulcerative colitis and Crohn's colitis compared to normal colon, we determined the distribution and quantitation of peptide histidine-methionine. Fresh surgical specimens were dissected into mucosal-submucosal and muscularis externa layers prior to acid extraction and specific radioimmunoassay. One immunoreactive species that appeared to coelute with peptide histidine-methionine was separated by reverse-phase high-performance liquid chromatography. Mucosal-submucosal concentrations of peptide histidine-methionine were significantly decreased in ulcerative colitis and Crohn's colitis, compared to those in normal colon. In normal ileum and colon, linear correlation analysis showed no relationship between patient age and tissue concentrations of peptide histidine-methionine. However, a parallel decrease in molar concentrations of peptide histidine-methionine and vasoactive intestinal polypeptide in ulcerative colitis and Crohn's colitis was demonstrated by linear correlation analysis. These results are consistent with the hypothesis that peptide histidine-methionine and vasoactive intestinal polypeptide are colocalized within the same neural structures that have been altered in the idiopathic inflammatory bowel diseases.

Adolescent↗

PubMed1988

Peptide YY concentrations in normal ileum and colon and in idiopathic inflammatory bowel disease.

Concentrations of the candidate endocrine and paracrine peptide, peptide YY, were measured by specific radioimmunoassay in tissue extracts prepared from normal ileum, normal colon, Crohn's disease, and ulcerative colitis. In both the ascending and descending colon, there were significantly decreased mean concentrations of peptide YY in Crohn's colitis and ulcerative colitis, compared to mean concentrations in normal colon. There was no age-related decrease of concentrations of peptide YY in normal colon. The decrease in concentrations of peptide YY in colon obtained from patients with inflammatory bowel disease did not appear related either to the duration of the clinical symptoms of the disease or to the severity of colonic inflammation. Further studies of the physiological function of peptide YY in man are needed to determine whether these findings might be useful in understanding a component of the pathophysiology of idiopathic inflammatory bowel disease.

Adolescent↗

PubMed1988

Somatostatin in the idiopathic inflammatory bowel diseases.

To study the effect of mucosal inflammation on tissue concentrations of somatostatin, the distribution and concentration of somatostatin in specimens of normal and abnormal (ulcerative colitis and Crohn's disease) ileum and colon were determined by a specific radioimmunoassay. Each tissue specimen obtained at surgery was separated by microdissection into the mucosa-submucosa and the muscularis externa. Immunoreactive somatostatin was acid-extracted from each layer before measurement. Gel chromatography was used to characterize immunoreactive somatostatin measured by radioimmunoassay; somatostatin-28 was the major immunoreactive species measured in human intestine. In normal colon, concentrations of somatostatin were not related to patient age. Concentrations of immunoreactive somatostatin in the mucosa-submucosa of the descending colon were significantly decreased in ulcerative colitis and in Crohn's colitis, compared with normal colon. There was no apparent relationship between concentrations of somatostatin and the duration of inflammatory bowel disease. However, somatostatin concentrations appeared to be lower in patients with severe colitis than in patients with minimal colitis. The decrease in mucosal-submucosal concentrations of somatostatin is in agreement with previous morphologic studies, which have suggested diminished populations of endocrine cells in ulcerative colitis. The possible role of somatostatin in the colon suggests that further studies of the alteration of this gut peptide may be useful in understanding a component of the pathophysiology of idiopathic inflammatory bowel disease.

Chromatography, Gel↗

PubMed1988

Concentrations of cholecystokinin, substance P, and bombesin in discrete regions of male and female rat brain: sex differences and estrogen effects.

The distributions of cholecystokinin, substance P, and bombesin was measured in discrete regions of the hypothalamus and limbic system in male and female rats. Higher levels of cholecystokinin immunoreactivity were determined for males compared with females during the estrous cycle in the posterior-medial aspect of the amygdaloid complex, bed nucleus of the stria terminalis, medial preoptic area, paraventricular nucleus, and ventromedial nucleus. The only region that always contained greater substance P immunoreactivity in the male was the posterior-medial amygdala. No sex differences were observed for the levels of bombesin immunoreactivity. During the estrous cycle, significantly lower levels of cholecystokinin immunoreactivity occurred during the morning of estrus in the posterior-medial amygdala, bed nucleus, median eminence, and ventromedial nucleus, whereas substance P immunoreactivity was lower on estrus in the bed nucleus and ventromedial nucleus. In the posterior-lateral aspect of the amygdala, females were observed to have more cholecystokinin immunoreactivity than males although no significant variations occurred during the estrous cycle. Bombesin-immunoreactive levels were unchanged throughout the estrous cycle in all regions assayed. In a separate experiment to test the hypothesis that estradiol enhances the release of cholecystokinin from terminals in the mediobasal hypothalamus, this region was dissected from ovariectomized and ovariectomized estrogen-primed rats and superfused with estradiol-17 beta. Indeed, exposure of the tissue to estradiol-17 beta was observed to enhance the K+-stimulated release of cholecystokinin from a mediobasal hypothalamic block in vitro. These results, as well as the variation of cholecystokinin during the estrous cycle, imply an important role for cholecystokinin in the regulation of steroid-initiated reproductive events.

Animals↗

PubMed1988

Spontaneous contractions and some electrophysiologic properties of circular muscle from normal sigmoid colon and ulcerative colitis.

Spontaneous contractions, inhibitory responses produced by electrical field stimulation, and some electrophysiologic properties of circular smooth muscle from normal sigmoid colon and from sigmoid colon of ulcerative colitis patients were compared in vitro using simultaneous recordings of mechanical and intracellular electrical activity. In normal colonic circular muscle obtained from 21 patients, the frequency of spontaneous summation contractions ranged from 3 to 7 per 4 min, whereas in circular muscle from 13 patients with ulcerative colitis, the frequency of these contractions ranged from 1 to 9 per 4 min. Nonadrenergic, noncholinergic relaxation produced by electrical field stimulation was recorded in the majority of circular smooth muscle strips from both normal colon and colon from patients with ulcerative colitis. There were no significant differences in mean resting membrane potential, mean slow-wave frequency, mean maximum slow-wave amplitude, or inhibitory-junction potential amplitudes recorded using circular smooth muscle from both normal colon and colon from patients with ulcerative colitis. There appeared to be a weak association in patients with ulcerative colitis between increasing duration of symptoms and decreasing frequency of spontaneous summation contractions, but there were no associations between the frequency of these contractions and the severity of colonic inflammation, patient age, or the frequency of stools. The mechanism accounting for a wider range in the frequency of summation contractions recorded from colonic circular smooth muscle in ulcerative colitis remains to be determined.

Adult↗

PubMed1988

Idiopathic chronic constipation is associated with decreased colonic vasoactive intestinal peptide.

To investigate the reported association between idiopathic chronic constipation and morphologic abnormalities of enteric nerves, we measured the concentrations of six neuropeptides, vasoactive intestinal peptide, peptide histidine-methionine, substance P, methionine5-enkephalin, neuropeptide Y, and the bombesinlike intestinal peptides, in descending colon from 4 patients with idiopathic chronic constipation. Decreased concentrations of vasoactive intestinal peptide (707 +/- 112 ng/g wet tissue) and peptide histidine-methionine (543 +/- 58 ng/g) were found in the muscularis externa obtained from constipated patients compared with normal concentrations (40 patients) of vasoactive intestinal peptide (1199 +/- 47 ng/g) and peptide histidine-methionine (815 +/- 45 ng/g). Vasoactive intestinal peptide was identified by immunocytochemistry in nerve fibers within the circular smooth muscle layer of descending colon obtained from 6 control patients, but not in nerve fibers within the circular smooth muscle of descending colon obtained from 3 patients with idiopathic chronic constipation. By contrast, the distribution of immunoreactive met5-enkephalin was similar in normal descending colon and in descending colon obtained from patients with idiopathic chronic constipation. Decreased colonic concentrations of vasoactive intestinal peptide (a candidate nonadrenergic, noncholinergic inhibitory neurotransmitter) may be associated with diminution of inhibitory innervation of colonic circular smooth muscle in some patients with idiopathic chronic constipation.

Adult↗