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Biomedical subjects

R H Hunt

Publications and source records attributed to R H Hunt.

At least 181 records · Page 10Linked to original sources
PubMed1988

Changes in rat and human pepsinogen phenotypes induced by N'-methyl-N'nitro-N-nitrosoguanidine.

Changes have been studied in human and rat pepsinogen phenotypes induced by N'-methyl-N'nitro-N-nitrosoguanidine (MMNG) in in vitro rat experiments and in vivo cultures of human and rat isolated gastric chief cells. In vivo the fastest migrating electrophoretic band decreased or disappeared as early as 3 weeks after the start of MNNG treatment. The changes, observed in 17 of 32 rats receiving MNNG, were permanent and consistently associated with pronounced histopathologic changes seen 10 months later (17 of 17). Comparable phenotypic changes were observed after 7 days only in MNNG-treated rat chief cell cultures. In human chief cell cultures a decrease of the Pg3 band, which is consistent with the "carcinogenic" phenotype, was observed in two of six preparations treated with MNNG. This early preceding change in phenotype preceding tumor formation may be useful as a diagnostic tool for the onset of gastric cancer.

Animals↗
PubMed1988

Control of pepsinogen synthesis and secretion in primary monolayer cultures of canine gastric chief cells.

We have studied pepsinogen synthesis and secretion in primary monolayer cultures of canine gastric chief cells. Monolayers were formed after approximately 48 hr. Pepsinogen synthesis was studied by adding 14C-labeled amino acids to the culture medium. Basal secretion of de novo synthesized pepsinogen after 4 hr was 4 +/- 1.2% of total newly synthesized pepsinogen. Basal secretion of stored pepsinogen after 90 min was 8 +/- 1.4% of total pepsinogen content. Carbachol, dbcAMP, forskolin, VIP, CCK-8, and the phorbol ester 12-O-tetradecanoyl-phorbol-13-acetate all stimulated secretion of de novo synthesized pepsinogen and preformed pepsinogen. Only additive interactions were found. dbcAMP caused a peak outburst of stored pepsinogen in the first 10 min. Carbachol stimulation was time dependent. Stimulation of de novo synthesized pepsinogen secretion was time dependent for both carbachol and dbcAMP. dbcAMP caused an immediate 10-fold increase in pepsinogen synthesis, but carbachol did so only after a lag time of 30 min. This was identical to the time necessary for the appearance of labeled pepsinogen in the medium. Addition of atropine after 2 hr resulted in a return to basal synthesis. Stimulated pepsinogen synthesis was always observed concomitant with stimulated pepsinogen secretion. These results show that most external stimuli for pepsinogen synthesis are dependent upon prior depletion of pepsinogen stores, which then triggers synthesis, while stimulation of cAMP production stimulates pepsinogen synthesis more directly.

Animals↗
PubMed1988

The treatment of gastric ulcer with antisecretory drugs. Relationship of pharmacological effect to healing rates.

Published clinical trials (N = 56) of antisecretory drugs in the treatment of benign gastric ulcer were reviewed. Composite healing rates for various drug regimens were calculated using a method previously described for duodenal ulcer. Healing rates were compared with data on suppression of intragastric acidity to see if any relationship was evident. No significant correlations between the two existed, unless placebo data were included in the analysis. Correlations were stronger with suppression of total 24-hr rather than nocturnal acidity. Using Williams' method for assessing trends, it was found that an increase in antisecretory effect is not associated with a concomitant increase in healing rates. Duration of medical treatment is the single most important factor in healing of benign gastric ulcer; healing rates for all drug regimens and placebo show a consistent increase with prolongation of treatment.

Anti-Ulcer Agents↗
PubMed1988

Omeprazole (20 mg daily) versus cimetidine (1200 mg daily) in duodenal ulcer healing and pain relief.

We conducted a double-blind, randomized, parallel group study in 169 patients with acute duodenal ulcers to compare omeprazole, 20 mg daily, with cimetidine, 600 mg twice daily. After 2 wk, 58% of the omeprazole-treated patients and 46% of the cimetidine-treated patients were completely healed (p = 0.056). After 4 and 6 wk 84% and 88% healed with omeprazole, and 80% and 89% healed with cimetidine (p = NS). After 2 wk, pain was completely gone in 62% of the omeprazole-treated patients versus 46% of the cimetidine-treated patients (p = 0.04). Clinical or laboratory adverse events were reported in 6 (7%) of the omeprazole-treated patients and 11 (13%) of the cimetidine-treated patients (p = NS). An adverse event caused withdrawal of 1 patient on omeprazole (anxiety and depression) and 2 patients on cimetidine (diarrhea and fall in hemoglobin). We conclude that omeprazole (20 mg daily) resulted in a trend toward more rapid ulcer healing compared with a relatively high dose of cimetidine (600 mg b.i.d.), and was preferred by patients for relief of ulcer pain.

Adult↗
PubMed1988

Changes in intestinal permeability and epithelial differentiation during inflammation in the rat.

We examined changes in gut permeability in a controlled model of inflammation produced in rats after infection with the nematode parasite, Nippostrongylus brasiliensis. The probe, 51Cr-EDTA, was injected into ligated loops of jejunum in vivo and recovery of radioactivity was measured in urine, kidney, and intact loop at five hours. Urinary recovery was significantly increased during the early (day 7) and acute (day 10) stages of the infection compared with values in control rats but subsequently returned to normal. Urinary clearance of the probe after iv injection was unaltered during infection. Villus atrophy occurred only at the stage, whereas crypt hyperplasia was evident at both the early and acute stages. The terminal ileum appeared normal and showed normal permeability when compared with controls. We conclude that permeability changes are local to the site of inflammation, are reversible after healing and may be related to an increase in the proportion of relatively undifferentiated epithelium.

Animals↗
PubMed1988

Alteration of H2 receptor sensitivity in duodenal ulcer patients after maintenance treatment with an H2 receptor antagonist.

The effects of a specific H2 receptor agonist impromidine, on gastric acid secretion were measured in six patients with duodenal ulcer in clinical remission before and after three months treatment with ranitidine 150 mg nocte. After treatment basal acid output increased from 1.2 to 2.8 mmol/h and after maximal impromidine stimulation from 36.9 (4.7) to 44.2 (6.2) mmol/h (p less than 0.02). Intravenous ranitidine 50 mg was given at the end of the impromidine infusion on each study day; the antisecretory effect of intravenous ranitidine was accentuated after the treatment with ranitidine from a trough acid output of 8.5 (1.2) mmol/h before, to 3.8 (1.5) mmol/h (p less than 0.05) after, treatment. The increased response to the H2 agonist impromidine and the H2 antagonist ranitidine after treatment with ranitidine suggests an enhanced sensitivity of the H2 receptor. This might be explained on the basis of an increase in the number of H2 receptors ('up-regulation').

Adult↗
PubMed1988

Prospective comparison of double contrast barium enema plus flexible sigmoidoscopy v colonoscopy in rectal bleeding: barium enema v colonoscopy in rectal bleeding.

Rectal bleeding often heralds serious colonic disease. The literature suggests that colonoscopy is superior to barium enema plus sigmoidoscopy, although no good comparative studies exist. Seventy one patients with overt rectal bleeding had prospectively flexible sigmoidoscopy, double contrast barium enema and colonoscopy completed independently. Against the gold standard, the sensitivity and specificity of colonoscopy were 0.69 and 0.78 respectively for a spectrum of colonic lesions, while for combined flexible sigmoidoscopy and double contrast barium enema these values were 0.80 and 0.56, respectively. When assessing adenoma or carcinoma, colonoscopy was more sensitive at 0.82 v 0.73, while flexible sigmoidoscopy plus double contrast barium enema was superior for detecting diverticular disease. The positive predictive value for colonoscopy was 0.87 against 0.81 for flexible sigmoidoscopy and double contrast barium enema. This study confirms that colonoscopy should be a first line investigation in subjects likely to require biopsy or therapeutic intervention.

Barium Sulfate↗
PubMed1988

Isolation and partial characterization of gastrotropin from canine ileum: further studies of the parietal and chief cell response.

Gastrotropin (GT), a protein previously isolated from porcine ileal mucosa, with a molecular mass of 14,054 daltons, was extracted from canine ileum and purified to homogeneity. The canine and porcine peptides had similar relative molecular mass, charge, hydrophobicity, and amino acid compositions. Direct Edman degradation yielded no free amino acids, indicating a blocked NH2-terminus, and a partial sequence determination of the CNBr fragments demonstrated a high degree of homology with porcine GT. Previous studies have indicated that GT is a potent enterooxyntin, and to further characterize these observations we have investigated the actions of both porcine and canine GT on isolated enriched preparations of guinea pig and dog parietal and chief cells. The results of these studies demonstrate that GT is present in more than one species and that the cellular response to porcine and canine GT is identical. The efficacies of canine and porcine GT preparations in stimulating pepsinogen secretion and [14C]aminopyrine uptake were identical and equal to those of cholecystokinin octapeptide (CCK8) and pentagastrin. GT was 100-fold more potent than either of these two major secretagogues. Maximal [14C]aminopyrine accumulation was observed with 10(-8) M GT, with an ED50 of 2 x 10(-9) M compared to pentagastrin, which caused maximal accumulation at 10(-6) M and had an ED50 of 5 x 10(-8) M. Maximal pepsinogen secretion was observed with 10(-7) M GT, with an ED50 of 10(-10) M, compared to 10(-6) M for CCK8, with an ED50 of 10(-8) M. The maximal chief cell response to GT was unaffected by the addition of CCK8 or carbachol, but responded additively with forskolin, indicating that GT uses the same transduction mechanism as CCK8 and carbachol and does not involve the activation of adenylate cyclase. The ED50 values observed with both parietal and chief cells in these studies were close to the basal circulating levels of GT (3.5 x 10(-9) M) in adult pigs. These results clearly demonstrate that GT is a potent component of the enterooxyntin factor identified in studies of the role of the small bowel in the regulation of gastric secretion.

Amino Acid Sequence↗
PubMed1988

The protective role of gastric acid.

This paper reviews the relationship between gastric acid secretion and infection and the protective role of gastric acid as a primary bactericidal barrier and modulator of gastrin section. Gastric acid is bactericidal at pH 3 or less, but reduction of acidity predisposes to infection with a wide variety of bacteria. Bacterial infections or hyperpyrexia may be associated with a marked reduction in gastric acid secretion, and Campylobacter pylori has been suggested as one cause of epidemic hypochlorhydria. Achlorhydria is also associated with hypergastrinaemia with levels 20-fold higher in pernicious anaemia patients than normal subjects. Treatment with antisecretory drugs is associated with hypergastrinaemia with gastrin levels 2- to 5-fold higher than with placebo, and the gastrin levels correlate with the degree of acid suppression. The possible relationship among infection, acid suppression, hypergastrinaemia, and the development of enterochromaffin cell hyperplasia and possible carcinogenesis is reviewed.

Achlorhydria↗
PubMed1988

Effect of immunologic reactions on rat intestinal epithelium. Correlation of increased permeability to chromium 51-labeled ethylenediaminetetraacetic acid and ovalbumin during acute inflammation and anaphylaxis.

In these studies we compared jejunal permeability to two probes--chromium 51-labeled ethylenediaminetetraacetic acid (51Cr-EDTA) (mol wt, 360) and ovalbumin (mol wt, 45,000)--under control conditions, during acute intestinal inflammation, and in response to systemic anaphylaxis. Acute inflammation was produced after infection with Nippostrongylus brasiliensis and rats were studied at day 0 (control), day 4 (early), day 10 (acute), and day 35 (postinfection). At the latter stage, immune rats were also studied during anaphylaxis induced by i.v. N. brasiliensis antigen. In each study, blood and urine were sampled over 5 h after the probes were simultaneously injected into ligated loops in anesthetized rats. In controls, small quantities (less than 0.04% and 0.002% of the administered dose for 51Cr-EDTA and ovalbumin, respectively) appeared in the circulation and plateaued at 1 h. During acute inflammation, the appearance of both probes continued to increase with time. Compared with controls, 5-h values for 51Cr-EDTA and ovalbumin were (a) significantly elevated at day 4 (p less than 0.005), (b) increased approximately 20-fold at day 10 (p less than 0.005 and less than 0.01, respectively), and (c) normal at day 35. Urinary recovery of 51Cr-EDTA followed the same pattern. During anaphylaxis, appearance of the probes in the circulation increased at 1 h to values approximately 10-fold those in controls (p less than 0.001 and less than 0.01, for 51Cr-EDTA and ovalbumin, respectively), and then declined. Urinary recovery of 51Cr-EDTA over 5 h was also significantly increased. We conclude that epithelial barrier function becomes impaired during both acute inflammation and anaphylaxis. In this rat model, gut permeability changes to 51Cr-EDTA reflect gut permeability changes to macromolecular antigens. If similar conditions exist in humans, urinary recovery of 51Cr-EDTA may be useful in monitoring intestinal abnormalities associated with inflammation.

Acute Disease↗
PubMed1988

Small bowel and colonic permeability to 51Cr-EDTA in patients with active inflammatory bowel disease.

51Cr-EDTA was administered both orally and per rectum via a catheter to controls and to patients with inflammatory bowel disease. The patients were divided into two groups, either with active inflammation of the small bowel or with active inflammation of the colon. Fifteen patients with Crohn's disease of the small bowel and 19 patients with either Crohn's disease of the colon or ulcerative colitis were investigated. After oral administration of the probe, controls showed a median excretion of 1.17%/24 h of the dose compared to 3.47%/24 h by patients with small bowel disease and 6.07%/24 h by patients with colonic disease. After rectal administration, controls showed a median excretion of 0.74%/24 h of the dose compared to 0.93%/24 h by patients with small bowel disease and 5.73%/24 h by patients with colonic disease. The rectal test differentiated small bowel disease from colonic disease with an accuracy of 85%. The results confirmed the inflamed colon as a site of increased intestinal permeation.

Adult↗