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Biomedical subjects

V L Go

Publications and source records attributed to V L Go.

At least 145 records · Page 8Linked to original sources
PubMed1985

Distribution and quantitation of immunoreactive gut neuropeptides in piebald mice and their normal littermates.

Piebald mice inherit congenital megacolon associated with distal aganglionosis. To study the distribution of intrinsic peptidergic nerves in the gut of piebald mice and their normal littermates, we used specific radioimmunoassays to measure the tissue concentrations of the following immunoreactive neuropeptides: vasoactive intestinal peptide (VIP), peptide histidine-isoleucine (PHI), [Met]enkephalin (Enk), substance P (SP), and bombesin-like intestinal peptide (BLIP). In the normal littermates, all neuropeptide concentrations were significantly greater in the colon than in the proximal gut. SP, Enk, VIP, PHI, and BLIP levels were all decreased in the distal colon of piebald mice as compared to normal littermates, SP, BLIP, and Enk levels were also decreased in the dilated proximal colon of piebald mice. These results suggest that there are abnormalities in the peptidergic innervation of the proximal and the distal colon in piebald mice. The abnormalities localized to the proximal colon of piebald mice may be related to functional obstruction of the colon.

Animals↗
PubMed1985

alpha-Glucosidase inhibition improves postprandial hyperglycemia and decreases insulin requirements in insulin-dependent diabetes mellitus.

In patients with diabetes mellitus, delayed increases in circulating insulin levels followed by prolonged hyperinsulinemia due to slow absorption of subcutaneously administered insulin hinders maintenance of euglycemia. To determine whether a delay in carbohydrate absorption would increase the effectiveness of subcutaneous insulin in controlling postprandial hyperglycemia in patients with insulin-dependent diabetes mellitus and whether it could allow insulin to be taken immediately prior to meals, the effects of an alpha-glucosidase inhibitor (Acarbose Boyer AG, Wuppertal, Germany) on postprandial plasma glucose profiles were determined in six subjects with insulin-dependent diabetes when a subcutaneous insulin infusion was started immediately or 30 minutes prior to meal ingestion. When 25% less insulin (9 v 12 units) was given along with Acarbose 30 minutes prior to meal ingestion, postprandial hyperglycemia decreased by 45% (areas under the curve, AUC, 8193 +/- 1960 v 14783 +/- 2260 mg/dL X min, P less than 0.02). When similar amounts of insulin (12 units) were given immediately prior to meal ingestion, postprandial hyperglycemia decreased 55% (AUC 6187 +/- 2240 v 13642 +/- 1579 mg/dL X min, P less than 0.001). These results indicate that delay in carbohydrate absorption improves the effectiveness of subcutaneous insulin in controlling postprandial hyperglycemia in patients with insulin-dependent diabetes mellitus and may permit satisfactory postprandial glycemic control when insulin is administered immediately prior to meal ingestion. Thus, an agent like Acarbose, which delays carbohydrate absorption, may be useful as an adjunct to insulin in the treatment of diabetes mellitus.

Absorption↗
PubMed1985

Neuropeptide levels in premenstrual syndrome.

To determine whether changes in circulating levels of neuropeptides are associated with symptoms of premenstrual syndrome (PMS), 20 women with the diagnosis of PMS and 20 asymptomatic subjects were studied. The premenstrual beta-endorphin levels were significantly lower in PMS patients (P = 0.0001). The decrease in beta-endorphin levels during the luteal phase, compared with the follicular phase, in PMS patients was also significant (P = 0.0002). Neurotensin, human pancreatic peptide, vasoactive intestinal polypeptide, gastrin, and bombesin-like immunoreactivity levels did not reveal significant changes between days 7 and 25 in patients with PMS.

Adolescent↗
PubMed1985

Can plasma human pancreatic polypeptide be used to detect diseases of the exocrine pancreas?

Plasma concentrations of human pancreatic polypeptide (HPP) parallel exocrine pancreatic secretion in response to stimulation with cholecystokinin. We determined prospectively the relationships among fasting HPP level, integrated HPP response to infusion of cholecystokinin, and output of trypsin and also the sensitivity, specificity, and predictive values of the fasting HPP level in the diagnosis of exocrine pancreatic disease. Our study group consisted of 19 patients with acute pancreatitis, 17 with chronic pancreatitis, and 25 with ductal adenocarcinoma of the pancreas and 27 control subjects. In the control patients and those with chronic pancreatitis, significant correlations were detected between HPP level and output of trypsin (P less than 0.001) in response to infusion of cholecystokinin and between fasting HPP and integrated HPP levels (P less than 0.004); no correlation was detected between HPP level and steatorrhea. The sensitivity, specificity, and negative and positive predictive values of the fasting HPP level for detection of either chronic pancreatitis or pancreatic cancer were similar and approximated 0.88, 0.67, 0.88, and 0.66, respectively. The HPP concentration had no value in detecting acute pancreatitis. Because the fasting HPP level has a high degree of negative predictability and is simpler to measure than the integrated HPP level or the output of trypsin, it may be a useful test in patients suspected of having either chronic pancreatitis or pancreatic cancer. A fasting HPP level of 125 pg/ml or greater could be used to exclude chronic pancreatitis or pancreatic cancer, but the finding of a value of less than 125 pg/ml necessitates use of other diagnostic tests for reliable determination of the presence of these diseases.

Acute Disease↗
PubMed1985

The complex of myxomas, spotty pigmentation, and endocrine overactivity.

Of 40 patients (16 males and 24 females), 29 had cardiac myxoma(s), 14 had skin pigmentation (lentigo and several types of nevi) which also commonly affected the lips, 6 had skin myxoma(s), and 12 had both pigmentation and myxoma(s); 18 had primary pigmented nodular adrenocortical disease (Cushing syndrome was present in 11); 10 had myxoid mammary fibroadenomas; 9 had testicular tumor(s) (large-cell calcifying Sertoli cell tumor, Leydig cell tumor, or adrenocortical rest tumor, or a combination); and 4 had pituitary adenoma with gigantism or acromegaly. The maximum number of conditions present together was five, occurring in two patients; each of the remaining patients had at least two of the conditions. The overlap, in this sizeable number of patients, of various combinations of the same rare or very rare conditions unlikely to occur together by chance with any degree of frequency is striking evidence for a unique syndrome. The patients were young (mean age at diagnosis of the first component, 18 years). Pathologic involvement tended to be multicentric (heart and skin) and bilateral in paired organs (adrenal, breast, and testis). Thirteen patients (32%) are alive and well. Twelve patients are alive but with complications of cardiac myxoma (in 8), testicular tumors (in 2), residual Cushing syndrome (in 1), or bilateral pulmonary nodules (in 1). Twelve patients are dead: 9 of cardiac myxoma, 1 of intracranial (nonpituitary) tumor, and 2 postoperatively. The status of three is unknown.

Adolescent↗
PubMed1984

Isolation and primary structure of human PHI (peptide HI).

The isolation of the human form of PHI (peptide HI) is described. The peptide was purified from human colonic extracts by using a chemical method for the detection of its C-terminal amidated structure. Human PHI consists of 27 amino acid residues and the complete amino acid sequence is: His-Ala-Asp-Gly-Val-Phe-Thr-Ser-Asp-Phe-Ser-Lys-Leu-Leu-Gly-Gln-Leu-Ser- Ala-Lys-Lys-Tyr-Leu-Glu-Ser-Leu-Met-NH2. The differences between the structures of porcine and human PHI are at position 12 (Arg/Lys replacement) and at position 27 (Ile/Met).

Amino Acid Sequence↗
PubMed1984

Action of intrathecal capsaicin and its structural analogues on the content and release of spinal substance P: selectivity of action and relationship to analgesia.

Intrathecal injections of capsaicin (CAP) and 4 other homovanillic acid (HMV) derivatives related to the structure of CAP were carried out. Capsaicin, 1-nonenoylvanillylamide (NVA), HMV-dodecylamide (DCA) (but not HMV-cyclohexylamide (CHA) or HMV-hexadecylamide (HDC] reduced the spinal content of substance P (SP), as measured by radioimmunoassay (RIA), and increased the tail-flick latency. Similar injection of kainic acid and piperine reduced levels of SP but failed to affect the tail-flick latency. None of the agents used affected spinal levels of cholecystokinin (CCK) or vasoactive intestinal peptide (VIP) as measured by RIA. In experiments using in vivo superfusion of the rat spinal cord, CAP, DCA and NVA were found to stimulate release of SP. Capsaicin had no effect on the levels of CCK or VIP immunoreactivity in the spinal superfusate. A tachyphylaxis to the effect of CAP and DCA on spinal SP release was demonstrated. Pretreatment with either agent blocked the releasing effect of the second. Pretreatment with an inactive analogue (HDC) had no effect on the subsequent activity of CAP. Kainic acid and piperine did not induce release of SP from the spinal cord. The relative selectivity of spinally administered capsaicinoids with regard to their effects on the content and release of peptides known to be contained in primary afferents and the presence of a similar structure-activity relationship for depletion and release of SP, desensitization and antinociception suggest the presence of a specific receptor site associated with a specific population of primary afferents through which pain information may pass. Whether SP is an 'afferent pain transmitter' is not clear, but at the least, it appears to serve as a marker for a population of afferents acted upon by spinally administered capsaicinoids.

Animals↗
PubMed1984

Acute and chronic morphine modifies the in vivo release of methionine enkephalin-like immunoreactivity from the cat spinal cord and brain.

The effect of acute and chronic morphine treatment was investigated on the spontaneous and evoked release of methionine enkephalin-like immunoreactivity (MELI) in vivo using the technique of cat spinal superfusion and ventriculocisternal perfusion. Stimulation of sciatic nerve, at intensities known to activate small-diameter nerve fibers, resulted in a consistent release of MELI from the spinal cord and the brain. Local application of morphine (5 X 10(-4)M) to the spinal cord resulted in a significant decrease in the evoked release of MELI. Naloxone (2 mg/kg i.v.), administered during morphine treatment, produced an increase in the spontaneous and greatly augmented the evoked release of spinal and ventricular MELI. In morphine-naive animals, naloxone did not affect the spontaneous or evoked MELI release. In cats chronically exposed to parenteral morphine by implantation of morphine pellets (2 X 75 mg), the spontaneous release of spinal and ventricular MELI was significantly greater than this release in control animals. Stimulation of sciatic nerves evoked a normal release of MELI in morphine-pelleted animals. Administration of naloxone to these animals resulted in a large and sustained increase in the spontaneous release of MELI from the spinal cord and brain. The material released by stimulation was identified as methionine enkephalin-like on the basis of similar results with two different antisera, parallel displacement curves with serial dilutions of spinal and ventricular perfusates and comigration with methionine enkephalin on a Sephadex G-25 column. These results suggest that if there is a tonic suppression of enkephalin release mediated by opiate receptors, these receptors display a tolerance development also. The facilitated release by naloxone in the chronic morphine-treated animals may indicate that reversal of the ongoing opioid inhibition results either in an excessive drive of the enkephalinergic neuron by other excitatory systems or the loss of a tonic auto-inhibition, which is not present in the non-tolerant animal.

Animals↗
PubMed1984

Initial clinical evaluation of an immunoradiometric assay for CA 19-9 using the NCI serum bank.

More than 1,600 coded sera obtained from blood donors and the NCI/Mayo Clinic Serum Bank were analyzed with an improved immunoradiometric assay for the carbohydrate antigenic determinant, CA 19-9. Results indicated that CA 19-9 is elevated in a large fraction of sera (67%) from patients with advanced adenocarcinomas of the upper gastrointestinal (GI) tract, including those with pancreatic, hepatobiliary and gastric carcinomas. Several of these sera had CA 19-9 exceeding 300,000 U/ml. A smaller fraction (18%) of patients with carcinomas of the large bowel had elevated serum CA 19-9 levels, the majority among patients with metastatic disease. In contrast, none of the healthy donors from the serum bank and only 4 of 1,023 of the blood donor specimens (0.4%) had CA 19-9 levels greater than or equal to 40 U/ml. Three of 235 sera (1.3%) from benign disease patients had levels of CA 19-9 in excess of 40 U/ml. These data suggest that the improved CA 19-9 immunoradiometric assay may have clinical utility as a diagnostic adjunct for adenocarcinoma of the upper GI tract and that the assay also may have some value in monitoring patients with advancing colorectal carcinoma, particularly in combination with CEA determinations. Rigorous prospective clinical trials will be necessary to verify these hypotheses.

Adenocarcinoma↗
PubMed1984

Simultaneous measurement of cholecystokinin- and vasoactive intestinal polypeptide-like immunoreactivity from cat frontal cortex in vitro: effect of morphine and D-Ala2-D-Leu5-enkephalin.

The two peptides vasoactive intestinal polypeptide (VIP) and cholecystokinin (CCK) have been demonstrated to be discretely distributed in the cerebral cortex. This distribution closely parallels the distribution of mu- and delta-opiate receptors in the frontal cortex. The basal efflux and potassium-stimulated release of VIP- and CCK-immunoreactivity was studied in the presence and absence of morphine and D-Ala2-D-Leu5-enkephalin (DADL), agents with relative affinity for the mu and delta receptors, respectively. The basal efflux of VIP- and CCK-immunoreactivity was not affected by these opiates; however, the potassium-stimulated release of VIP-immunoreactivity was profoundly inhibited in a dose-dependent manner by both morphine (ED50 = 1 X 10(-9) M) and DADL (ED50 = 3.02 X 10(-9) M). The inhibition produced by either morphine or DADL was shown to be reversed by naloxone.

Animals↗
PubMed1984

Studies on the opiate receptor-mediated inhibition of K+-stimulated cholecystokinin and substance P release from cat hypothalamus in vitro.

The addition of 50 mM K+ to the perfusate of cat hypothalamic slices results in a 3.4- and 5.5-fold increase in the levels of cholecystokinin (CCK) and substance P (sP) like immunoreactivity, respectively. The addition of morphine (10(-11)-10(-8) M; a mu receptor agonist) and D-Ala2-D-Leu5-enkephalin (DADL: 10(-12)-10(-10) M; a delta receptor agonist) resulted in a dose-dependent suppression of the K+-evoked release. SKF10047 (a sigma receptor ligand) and U50488H (a kappa receptor ligand) had no effect in doses up to 10(-6) M. Naloxone added with the lowest dose of agonist producing a maximal inhibition produced a dose-dependent reversal of the anti-release effects of morphine and DADL. The IC50 of naloxone for the antagonism by DADL and morphine of the release of CCK were similar, whereas the naloxone IC50 was lower for morphine than DADL in the reversal of the effects of the agonist in sP release. Within the constraints of receptor selectivity of the several ligands, these data suggest that at least two populations of opioid receptors (mu and delta) may be discriminated which govern the release of hypothalamic sP.

Animals↗
PubMed1984

Clinical relevance of regulatory gastrointestinal peptides.

The application of radioimmunoassay of insulin, C-peptide, gastrin, glucagon, vasoactive intestinal polypeptides (VIP), somatostatin, human pancreatic polypeptides (hPP), substance P and neurotensin to detect endocrine tumors of the pancreas and other organ systems is undoubtedly important in the clinical management of patients suspected of having tumors that secrete these hormones. Radioimmunoassays of the above gut peptides have certain degrees of specificity and sensitivity; however, there are several factors that need to be considered in the interpretation of results since heterogeneity of molecular forms does occur and the varied radioimmunoassay techniques use different antibodies that may yield different results. It is, therefore, important that each laboratory establish its own normal values, determine the molecular species that each assay is detecting, and also determine the false positivity of the methodology. The same endocrine tumor may contain and secrete several detectable peptides, but the syndrome may relate to only one peptide. Although the simultaneous measurement of multiple peptides in patients with benign gastrointestinal disease has yielded information that contributes to our understanding of the complexities of gut neuroendocrine interaction, the pathophysiological role of gut peptides and their clinical relevance need further evaluation.

Animals↗
PubMed1984

Characterization of cholecystokinin from the human brain.

Human forms of cholecystokinin have not previously been characterized chemically. In this study, we have extracted and purified the predominant molecular form of cholecystokinin present in human cerebral cortex. The peptide was characterized by amino acid analysis, automated peptide sequencing, and fast atom bombardment mass spectrometry. It appears to be identical to porcine cholecystokinin-octapeptide, with the sequence of Asp-Tyr(SO3)-Met-Gly-Trp-Met-Asp-Phe(NH2). This structural identity is consistent with the observations that the peptide in human brain and porcine cholecystokinin-octapeptide are recognized similarly by a battery of antisera to porcine cholecystokinin; that they coelute from several chromatographic systems, including gel filtration, ion exchange, and reversed-phase; and that they possess similar biological activities.

Brain Chemistry↗
PubMed1984

Innervation of the muscularis mucosae of canine proximal colon.

The innervation of the muscularis mucosae of the canine large intestine was studied in vitro using superfusion and radioimmunological techniques. In the majority of preparations, electrical field stimulation (10 V, 200 microseconds, 10 Hz) elicited a biphasic neurogenic response which consisted of a contraction followed, after cessation of the stimulus, by relaxation. Electrical field stimulation released VIP-, substance P- and bombesin-like immunoreactivity. Release of these peptides and the biphasic response to nerve stimulation were blocked by tetrodotoxin and a 'calcium-free' solution. Several observations suggest that neuronally released substance P (or a closely related peptide) mediated the contraction by a direct action on the muscle. The contraction caused by substance P was tetrodotoxin insensitive. Desensitization to substance P abolished the excitatory response to nerve stimulation. The contraction elicited by nerve stimulation was blocked by substance P antiserum. Several observations suggest that bombesin or a closely related peptide caused contraction of the muscle by releasing substance P from intramural neurones. Bombesin caused an increase in substance P-like immunoreactivity in the superfusate which was blocked by tetrodotoxin, as was the contraction; substance P antibodies blocked the contractile response to bombesin. In addition, while the excitatory response to electrical nerve stimulation was blocked by substance P antiserum, there was still an increase in bombesin-like immunoreactivity in the superfusate. The data also suggest that VIP or a closely related peptide might have mediated the relaxation by a direct action on the muscle. The inhibitory response to nerve stimulation was mimicked by VIP and abolished by VIP antiserum.

Animals↗
PubMed1984

Gastric inhibitory polypeptide in obesity and diabetes mellitus.

Gastric inhibitory polypeptide (GIP) concentrations may be influenced by obesity, diabetes, and glucagon deficiency and be under feedback inhibition by insulin. To assess these factors, insulin-dependent diabetic, totally pancreatectomized diabetic, and lean and obese noninsulin-dependent diabetic patients were studied twice, once during partial insulin withdrawal and again when euglycemia was achieved before and after mixed meal ingestion, using an artificial endocrine pancreas. The results were compared to those from weight-matched lean and obese nondiabetic subjects. No significant differences in postprandial GIP responses were found between lean and obese nondiabetic subjects. Despite basal and postprandial hyperglycemia, the GIP responses to the mixed meal were not significantly different between insulin-deficient (insulin-dependent and totally pancreatectomized) patients and lean nondiabetic subjects. In addition, there were no significant differences in postprandial GIP responses between insulin-dependent and totally pancreatectomized patients. In contrast, lean and obese noninsulin-dependent diabetic patients had reduced GIP responses compared to weight-matched nondiabetic subjects (mean +/- SE, 37.9 +/- 5.4 vs. 67.1 +/- 10.8 ng ml-1 240 min-1, respectively; P less than 0.05). This difference was entirely due to the reduced GIP responses in obese noninsulin-dependent diabetic patients compared to those in obese nondiabetic subjects (32.1 +/- 7.9 vs. 76.9 +/- 18.2 ng ml-1 240 min-1, respectively; P less than 0.05); the postprandial GIP responses were not significantly different between lean noninsulin-dependent diabetic patients and lean nondiabetic subjects. Insulin infusion by an artificial endocrine pancreas resulted in postprandial insulin and glucose profiles that approximated those of nondiabetics, but did not significantly alter GIP responses to the mixed meal (48.2 +/- 5.5 ng ml-1 240 min-1) in the 18 diabetic patients compared to results obtained with sc insulin treatment (42.2 +/- 5.2 ng ml-1 240 min-1). In conclusion, postprandial GIP responses are normal in obese nondiabetic subjects and insulin-deficient diabetic patients and are blunted in obese, but not in lean, noninsulin-dependent diabetic patients. In addition, GIP does not appear to be under feedback inhibition by insulin or influenced by glucagon deficiency in diabetes.

Adult↗
PubMed1984

Effect of opiate and adrenergic blockers on the gut motor response to centrally acting stimuli.

Labyrinthine stimulation and cold pain inhibit feeding antral pressure activity, delay gastric emptying, and increase blood concentrations of beta-endorphin and norepinephrine. Further, labyrinthine stimulation induces, in approximately one-third of healthy individuals, a migrating burst of motor activity in the proximal intestine that interrupts the normal fed pattern. Our hypothesis was that endogenous opiates and catecholamines act as mediators of such disruptive effects of centrally acting stressful stimuli on gut motility. Thus, we studied feeding gastrointestinal pressure activity in healthy volunteers who were exposed to labyrinthine stimulation or cold pressure test, or both (both stimuli being either in their active or in their control forms), while receiving an intravenous infusion of either placebo (saline), or an opioid blocker (naloxone), or a combination of alpha- and beta-adrenergic blockers (phentolamine and propranolol), or all the drugs together. Neither opioid nor adrenergic blockers affected motility during control stimulations. Active stressful stimuli (labyrinthine stimulation, cold pain, or both) significantly inhibited antral feeding activity (p less than 0.05), but these effects were prevented by concomitant infusion of naloxone (p less than 0.05). Adrenergic blockade also prevented the antral motor inhibition caused by stress (p less than 0.05), but it was more effective for cold pain than for labyrinthine stimulation, and, when performed concomitantly with opiate blockade, the preventive effects disappeared. Furthermore, during adrenergic blockade labyrinthine stimulation invariably induced the appearance of a migrating duodenal burst of motor activity. Neither opioid nor adrenergic blockers modified the stress-induced rise of plasma beta-endorphin and norepinephrine. Our results suggest that opioids and catecholamines are involved in the mediation of the disruptive effects induced by centrally acting stressful stimuli on postprandial motor activity in the proximal human gut.

Adult↗
PubMed1984

Prednisone for chronic active hepatitis: pharmacokinetics and serum binding in patients with chronic active hepatitis and steroid major side effects.

The response of serum prednisolone to a single oral dose of 30 mg of prednisone was studied in 12 patients with chronic active hepatitis taking prednisone, and in six healthy volunteers. Five of the 12 patients developed major side effects with prednisone, and seven showed less or no side effects. The patients with major side effects generally had higher serum bilirubin and lower serum albumin levels than the others. Prednisolone peak levels were similar in the three groups. Unbound (free) serum prednisolone was higher at 2, 3, 4, and 8 hours, in patients with chronic active liver disease and major side effects, than in the other two groups. Studies in vitro showed that protein binding of prednisolone increased with increasing albumin concentrations, and that bilirubin could displace some bound prednisolone. We suggest that the association between major side effects, hypoalbuminemia, and hyperbilirubinemia in patients with chronic active hepatitis is attributable to increased serum unbound prednisolone caused by: 1) limited availability of binding sites (hypoalbuminemia), or 2) displacement of bound steroid by competition (hyperbilirubinemia).

Adult↗