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Biomedical subjects

V L Go

Publications and source records attributed to V L Go.

At least 181 records · Page 10Linked to original sources

The role of tumor markers in the management of colorectal cancer.

Among the tumor-associated antigens evaluated for the diagnosis and management of cancer, carcinoembryonic antigen (CEA) is the only established and clinically useful tumor marker for colorectal cancer and other CEA-producing tumors. Because of the exhaustive studies in the past decade, a consensus development conference was held at NIH in September 1980, to address the issue concerning the role of CEA as a marker in the management of cancer. This conference concluded that the use of regular and sequential assays of blood CEA is the best noninvasive technique for postoperative surveillance of patients to detect disseminated recurrence of colorectal cancer. The CEA level can serve as an indicator of successful or incomplete resection, and is useful in monitoring the effect of chemotherapy or radiotherapy. CEA can also provide a useful estimate of prognosis. CEA is neither sensitive nor specific enough to be used in routine screening for possible malignancy in an asymptomatic population. Nor can this test independently establish a diagnosis of cancer, but it can be used as an adjunct to clinical staging methods in known cancer patients. Radioimmunodetection and radioimmunotherapy with anti-CEA antibodies are currently being evaluated. Study of the pathophysiology and metabolism of CEA is needed. CEA remains the prototype tumor marker and is a valuable comparative tool, when investigating the clinical value of other newly developed tests for tumor markers.

Carcinoembryonic Antigen↗

Opiate-mediated inhibition of the release of cholecystokinin and substance P, but not neurotensin from cat hypothalamic slices.

The neuroactive peptides neurotensin (NT), substance P (SP) and cholecystokinin (CCK) have been shown to be distributed in the hypothalamus. These peptides may be part of hypothalamic mechanisms which regulate the release of pituitary hormones and feeding behavior. Numerous experiments have demonstrated opiate modulation of anterior pituitary hormone release. These effects have been reported to be mediated via a hypothalamic mechanism, which modulates the secretion of releasing, release inhibiting factors or other neuroactive peptides such as SP, CCK and NT. We have examined the effects of morphine on the potassium-stimulated, calcium-dependent release of SP, CCK and NT from cat hypothalamic slices. The potassium-stimulated release of SP and CCK was profoundly depressed by the addition of morphine (10(-5) M) in a naloxone-reversible manner. This morphine inhibition was shown to be stereospecific, levorphanol (10(-7) M) depressed the release, while dextrophan (10(-7) M) was inactive. Gel filtration chromatography of the potassium-stimulated release was determined to be isographic with authentic NT, SP and CCK-8, respectively. There was no indication of any gastrin-like activity. These data may suggest a regulatory mechanism through which opiates exert some of their neuroendocrine or feeding regulatory effects.

Animals↗

Origin and distribution of cholecystokinin-containing nerve terminals in the lumbar dorsal horn and nucleus caudalis of the cat.

Immunohistochemical bridge methods were used to localize cholecystokinin (CCK)-like immunoreactivity in the lumbar dorsal horn (DH) and nucleus caudalis (NC) of the cat. The CCK-positive structures were either dot- or fiber-like. The distribution of CCK-like immunoreactivity in the DH and NC was narrower than substance P (SP)-like immunoreactivity in adjacent sections. CCK- and SP-like immunoreactivity in the DH and NC was severely depleted 7--10 days following rhizotomy of either the dorsal roots or the 5th, 9th and 10th cranial nerves, respectively; enkephalin-like immunoreactivity in adjacent sections was unaffected. Cervical hemisection had no effect on either CCK- or SP-like immunoreactivity in the DH.

Animals↗

Studies on the location and release of cholecystokinin and vasoactive intestinal peptide in rat and cat spinal cord.

By radioimmunoassay vasoactive intestinal peptide (VIP) and cholecystokinin (CCK) are found in the cat lumbar spinal ganglion and spinal cord with levels in dorsal greater than ventral horn. Unilateral rhizotomy, but not cervical hemisection produced a significant but incomplete depletion of CCK and VIP immunoreactivity in dorsal, but not ventral horn. Intrathecal capsaicin (0.5 mg) had no effect on the levels of spinal VIP or CCK. Intrathecal colchicine (0.5 mg)produced a significant increase in the levels of VIP in the dorsal and ventral horn but had no effect on the levels of CCK. The present experiments, using a preparation which permits in situ superfusion of the spinal cord, demonstrated in the chloralose-urethanized cat and rat the presence of measurable levels of VIP and CCK. In rats, the addition of potassium (40 mM in excess) resulted in a 138% and 46% increase in the levels of CCK and VIP, respectively above resting levels (3.7 +/- 1.2 fmol/ml/10 min and 1.7 +/- 0.5 fmol/ml/10 min, respectively). The deletion of calcium and substitution of cobalt (2 mM) resulted in a significant reduction in the potassium-evoked release. Intrathecal picrotoxin doubled the levels of CCK, but had no effect on the levels of VIP in the spinal superfusates. Capsaicin (3 X 10(-4) M) had no effect on the levels of either peptide in rat spinal superfusate. In cats, bilateral electrical stimulation of the sciatic nerve at high, but not low intensity, resulted in a 218% and 132% increase above prestimulation baseline in the levels of CCK and VIP, respectively. Separation of immunoreactivity on a Sephadex G-50 superfine column of the spinal superfusates and the extracted material from cat spinal cord, revealed that the immunoreactive CCK species in tissue co-migrated with the 8 and 33 amino acid peptide fragments. In the release samples, however, all the radioimmunoassayable activity migrated with the peak corresponding with CCK. No other peaks were detected. Column separation of spinal cord and the superfusate obtained during basal and evoked release, revealed that all activity in both the tissue and perfusate samples, travelled in a single peak which co-migrated with authentic VIP.

Animals↗

Relationships between pancreaticobiliary ductal anatomy and pancreatic ductal and parenchymal histology.

To determine whether ductal or parenchymal histologic abnormalities were related to the type of openings of the pancreatic duct and common bile duct into the duodenum, 390 unfixed human postmortem en bloc pancreaticoduodenal specimens were examined anatomically, radiographically, and histologically. In 353 specimens, ductal openings were classifiable: 25% had a well-defined ampulla, 18% a long common channel, 31% a short common channel, 7% an interposed septum, and 19% had separate openings for the pancreatic and bile ducts. Ductal histologic abnormalities were present in 25% of the specimens and most (77%) were found in the pancreatic head. When ductal openings were grouped according to the presence or lack of a prominent common channel, ductal epithelial abnormalities were more common in the absence of a prominent common channel (30% vs. 19%, p less than 0.04). Papillary epithelial hyperplasia was associated only with the absence of a prominent common channel (P = 0.02). Histologic abnormalities were more common in the elderly (P less than 0.005) but were not associated with cause of death or the presence of the minor pancreatic duct. Lack of a common channel is associated with abnormal ductal epithelium. This anatomic arrangement may be a factor in pancreatic carcinogenesis.

Age Factors↗

Human interdigestive and postprandial gastrointestinal motor and gastrointestinal hormone patterns.

Fasting gastrointestinal motor and hormone patterns were studied in 11 healthy volunteers. Cyclic motor activity was present in all subjects during fasting, but the duration and site of onset of each cycle were variable, even in the same subject. Fasting gastrin, GIP, and glucagon levels remained low and constant during the 8-hr study, while plasma motilin levels exhibited cyclic variation in 7 of the 11 subjects. Achlorhydria (induced with cimetidine in 5 of the 11 subjects) did not alter the pattern of fasting motor activity or plasma motilin. In the remaining six subjects, the effect of liquid nutrient meals was examined. Ingestion of a sodium chloride bolus failed to disrupt fasting cyclic activity, while all nutrient-containing solutions inhibited gastric phase-2 motor activity, the duration of inhibition being longest for the mixed and lipid meals. All nutrient meals released GIP, while only protein and mixed meals released gastrin, and the lipid meal released motilin. Our study confirms the rhythmicity of interdigestive motor cycles in man and demonstrates their lack of dependence on gastric acid secretion and some relationship to motilin cycles in certain individuals as determined by radioimmunoassay. Transition from fasting to fed pattern (after liquid meals) is characterized by the inhibition of phasic gastric pressure changes in the antrum and the development of irregular activity in the intestine, similar in pattern to fasting phase 2. Because the duration of interruption of the gastric interdigestive pattern by meals depends on their nutrient content, we conclude that dietary composition may be a major determinant of the fasting-fed motor balance in man.

Achlorhydria↗

Glucagon, gastric inhibitory polypeptide and the gastrocolic response.

Serosal bipolar electrodes and strain gauge force transducers were placed on the right and left colon in subhuman primates to record spike discharges and circular muscular contractions. The effect of glucagon on colonic motor and electrical activity were studied before and after meals. Serum concentration of gastric inhibitory polypeptide was measured simultaneously 15 minutes before and 45 minutes after eating. Serum levels of gastric inhibitory polypeptide increased in response to eating; pre- and postcibal concentrations were not altered by glucagon. The gastrocolic response of the colon to eating was demonstrated. Glucagon inhibited the intrinsic activity of the entire colon before meals and partly inhibited the right colon after meals. Postcibal left colon activity was not inhibited by glucagon. This indicates that a distinct mechanism accounts for the left colonic postcibal increase in contractile and electrical spike activity. A neural or humoral mechanism is implicated but is not specifically identified.

Animals↗

Endocrine pancreatic response of children with onset of insulin-requiring diabetes before age 3 and after age 5.

The increased incidence of severe hypoglycemia reported in young children with diabetes is consistent with a defect in glucagon secretion or a generalized abnormality in islet hormone secretion. To assess pancreatic hormone and gastric inhibitory polypeptide secretion in children with early onset diabetes, 12 children with onset of diabetes prior to the age of 28 months were studied and the data compared to the hormone responses observed in 11 children with LOD, diagnosed after the age of 5 years. Plasma glucose, C-peptide, glucagon, pancreatic polypeptide, and gastric inhibitory peptide concentrations were measured during and following an arginine infusion (500 mg/kg over 60 minutes) and a mixed meal. During arginine infusion, plasma glucose and glucagon increased similarly in both groups and returned to basal concentrations following discontinuation of arginine infusion. In contrast, plasma C-peptide, hPP, and GIP concentrations did not change. Following the mixed meal plasma glucose, hPP, and GIP concentrations increased similarly in the two groups of children, but no change was observed in either plasma glucagon or C-peptide concentrations in either group. These data demonstrate that EOD and LOD are associated with insulin insufficiency alone and that abnormalities in secretion of other pancreatic islet hormone or GIP cannot be implicated in the high incidence of severe hypoglycemia observed in children with EOD.

Arginine↗

Pancreatic exocrine function in severe human chronic renal failure.

Patients with chronic renal failure have an abnormal immunoreactive gastrointestinal hormone profile, which is characterised by raised fasting serum concentrations of hormones that have antagonistic effects on exocrine pancreatic function. In addition, in this present study we have found that in renal insufficiency cholecystokinin disappears slowly from the plasma after a constant intravenous infusion of the hormone (p = 0.05 compared with healthy subjects). To evaluate whether the stimulatory or inhibitory hormones have a predominant effect, pancreatic exocrine function under conditions of mannitol perfusion of the duodenum and continuous intravenous cholecystokinin stimulation was studied in eight patients who had severe chronic renal failure and eight age-matched and sex-matched control subjects. Compared with healthy subjects, patients with renal insufficiency had hypersecretion of trypsin in response both to mannitol perfusion of the duodenum and to cholecystokinin stimulation (p less than 0.05). No significant differences in lipase secretion were noted between the patients with renal insufficiency and control subjects. These findings are consistent with the hypothesis that, of the abnormally raised fasting serum concentrations of gastrointestinal hormones found in renal insufficiency, hormones that stimulate rather than inhibit pancreatic exocrine function predominate. Secondly, the dissociation between trypsin and lipase outputs in chronic renal failure may suggest a differential trophic influence of stimulatory hormones -- that is, hypercholecystokininaemia -- on pancreatic exocrine enzyme secretion.

Adult↗

Physiology of 24,25-dihydroxyvitamin D3 in normal human subjects.

We determined the metabolic clearance and production rates of 24,25-dihydroxyvitamin D3 in four normal healthy adults. We also examined the excretion of radioactivity in stool, urine, and bile after the intravenous administration of 24,25-[3H]dihydroxyvitamin D3 to human subjects. 24,25-Dihydroxyvitamin D3 is rapidly cleared from the plasma with a half-life of approximately 390 +/- 25 min (mean +/- SE). The metabolic clearance rate of 24,25-dihydroxyvitamin D3 was 9.2 +/- 1.5 liters/day with a production rate of 26.4 +/- 7.2 micrograms/day (mean +/- SE). Within 1 day 13.0 +/- 4.2% (mean +/- SE) of the administered dose had appeared in the stool; by day 7, 48.8 +/- 2.7% of the dose had appeared in the feces. Within 24 hr, 6.4 +/- 0.8% of the administered dose appeared in the urine; 7.4 +/- 1.8% of the dose had appeared in the urine within 2 days. The biliary excretion of 24,25-dihydroxyvitamin D3 was studied in two subjects. By 8 h, 15.3 +/- 1.3% of the administered dose had appeared in the bile. The metabolites present in bile, feces, and urine were much more polar than 24,25-dihydroxyvitamin D3. These results demonstrate that 24,25-dihydroxyvitamin D3 is rapidly cleared from plasma and is excreted in the feces (probably via the bile) and urine of normal human subjects.

24,25-Dihydroxyvitamin D 3↗

Nutrient and bowel segment dependency of human intestinal control of gastric secretion.

The gastric secretory effects of protein, fat, and carbohydrate infused at different levels of the small bowel were investigated in seven healthy subjects. Similar caloric loads (53.4 kcal) of protein (essential amino acids), lipid (oleic acid), and carbohydrate (glucose) in isomolar (280 mosmol/l) similar pH (7.4) solutions were infused into 60-cm segments of small bowel (isolated between two occlusive balloons), located distal to the ligament of Treitz (proximal), proximal to the ileocecal valve (distal), and between the two (middle). A submaximal gastric secretory background was provided by continuous intravenous pentagastrin. Protein stimulated acid secretion in the proximal (increase of 8.7 meq/h, representing 84 +/- 5% of control level) and middle (increase of 1.9 meq/h, representing 16 +/- 2% of control level) segments, while it inhibited acid secretion when infused into the distal segment (decrease of 3.7 meq/h, representing 33 +/- 4% of control level). In contrast, both lipid and carbohydrate inhibited acid secretion similarly (33-38% of control level) at all levels of the bowel. The different effects of protein at different levels of the bowel could not be explained by differences in serum gastrin, different degrees of absorption, or different postabsorptive levels of alpha-amino nitrogen. This suggests the presence of hormonal (nongastrin) or neural mechanisms in the proximal bowel to stimulate acid secretion and/or in the distal bowel to inhibit acid secretion. Thus, factors that determine specific nutrient loads to specific segments of bowel can have important physiological effects on gastric acid secretion.

Adolescent↗

Innervation of the muscularis mucosa in the canine stomach and colon.

A preliminary report is presented of studies into the innervation of the canine muscularis mucosa. In vitro experiments have investigated the mechanical response to electrical stimulation and the release of gut peptides known to modulate gastrointestinal function. Exogenous substance P increased tone and amplitude of phasic contractions while neurotensin and vasoactive intestinal polypeptide (VIP) relaxed the muscularis mucosa. Immunoreactive VIP was released into the superfusate during transmural electrical stimulation of the antrum while VIP and substance P were present in superfusate from the colon. The significance of these findings has been discusses briefly.

Animals↗

Laboratory diagnosis of gastrinoma. II. A prospective study of gastrin challenge tests.

A prospective study of the value of secretin, calcium, and meal gastrin challenge tests for the diagnosis of gastrinoma indicated that the secretin test may be valuable. The calcium test was equally valuable, but it cannot be recommended as enthusiastically because it is time-consuming and may cause side effects. New criteria for interpretation of these tests were based on peak responses to the challenge. Further, the study revealed that patients with hypochlorhydria and hypergastrinemia could be identified without the use of gastric analysis. This prospective study reflects the current pattern of clinical practice at a referral institution where patients with gastrinoma, an unusual condition, are seen with regularity. The criteria we propose for interpretation of these tests are simple and could be applied to individual patients in whom a gastrinoma is suspected.

Adolescent↗

Canine intestinal ulcer: myoelectric components and the effect of chronic hypergastrinemia.

The effects of jejunal ulcer and chronic endogenous hypergastrinemia on canine gastrointestinal myoelectric activity were investigated in three groups of dogs. All dogs were chronically implanted with electrodes on the stomach and either the duodenum or jejunum. Fasted-state myoelectric activity was monitored before and after gastroenterostomy. Two groups of dogs underwent autotransplantation of the gastric antrum to the midcolon with either gastroduodenostomy or gastrojejunostomy. The third group of dogs underwent diversion of the antroduodenum with gastrojejunostomy. Chronic hypergastrinemia was observed postoperatively in the dogs of each of the three models. Only dogs with gastrojejunostomy and antrocolic transplant developed intestinal ulcers. None of the dogs, despite the presence of ulcers in one group, demonstrated significant changes in myoelectric activity. In both gastrojejunostomy models, a trend toward lengthened interdigesive phase 2 at the expense of phase 1 was seen. No other myoelectric changes were observed and chronic hypergastrinemia had no effect on myoelectric activity in these models. We conclude; (a) experimental jejunal peptic ulcer is not marked by significant changes in interdigestive myoelectric activity and (b) chronic hypergastrinemia is not accompanied by the gastrointestinal muscle, effects reported after acute treatment with gastrin, suggesting a tolerance.

Animals↗