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Biomedical subjects

M F Go

Publications and source records attributed to M F Go.

49 records · Page 3Linked to original sources
PubMed1995

Cluster analysis of Helicobacter pylori genomic DNA fingerprints suggests gastroduodenal disease-specific associations.

BACKGROUND: Helicobacter pylori infection is now accepted as the most common cause of chronic active gastritis and peptic ulcer disease. The etiologies of many infectious diseases have been attributed to specific or clonal strains of bacterial pathogens. Polymerase chain reaction (PCR) amplification of DNA between repetitive DNA sequences, REP elements (REP-PCR), has been utilized to generate DNA fingerprints to examine similarity among strains within a bacterial species. METHODS: Genomic DNA from H. pylori isolates obtained from 70 individuals (39 duodenal ulcers and 31 simple gastritis) was PCR-amplified using consensus probes to repetitive DNA elements. The H. pylori DNA fingerprints were analyzed for similarity and correlated with disease presentation using the NTSYS-pc computer program. RESULTS: Each H. pylori strain had a distinct DNA fingerprint except for two pairs. Single-colony DNA fingerprints of H. pylori from the same patient were identical, suggesting that each patient harbors a single strain. Computer-assisted cluster analysis of the REP-PCR DNA fingerprints showed two large clusters of isolates, one associated with simple gastritis and the other with duodenal ulcer disease. CONCLUSIONS: Cluster analysis of REP-PCR DNA fingerprints of H. pylori strains suggests that duodenal ulcer isolates, as a group, are more similar to one another and different from gastritis isolates. These results suggest that disease-specific strains may exist.

Adult↗
PubMed1995

Helicobacter pylori, duodenal ulcer, gastric cancer: tunnel vision or blinders?

The focus of this paper is on the relationship between Helicobacter pylori gastritis and gastric cancer, one of the most compelling issues after the recent decision of the IARC (International Agency for Research on Cancer) to categorize H. pylori as a carcinogen. Our aim is to identify areas where additional work is not needed and suggest new directions of inquiry. We review what has been accomplished with the advantage of hindsight. Our review of the data regarding current putative virulence factors found that disease and outcome specificity were lacking. The same can be said of the data regarding low gastric juice ascorbate or increased mucosal cell turnover in H. pylori gastritis. We conclude that, while it is certainly possible that some of the factors discovered to date may initiate or mediate certain pathogenetic aspects of H. pylori-related disease, none of them can be seriously proposed as the factor responsible for either gastric cancer or duodenal ulcer. Finally, we identified research areas that might lead to disease-specific associations as well as areas where helicobacters may be used as models for other diseases. We propose that it is time to pause, reflect on what has been done, and focus more sharply on the questions that remain unanswered.

Duodenal Ulcer↗
PubMed1994

How does Helicobacter pylori cause duodenal ulcer disease: the bug, the host, or both?

Helicobacter pylori infection is the most common cause of duodenal ulcer disease, yet duodenal ulcer is an uncommon outcome of H. pylori infection. We reviewed the possible explanations such as differences in the host or in the strain of H. pylori. Host factors reviewed included genetic susceptibility to H. pylori infection and excess gastric acid secretion. The role of potential H. pylori virulence factors not present in all strains such as the cagA gene and the results of other molecular methods to identify disease-specific differences among isolates was also reviewed. Although cure of H. pylori infection resolves gastrin releasing peptide stimulated acid secretion there was no change in parietal cell mass. Twin studies have shown genetic differences in H. pylori susceptibility. There was no difference in the prevalence of the cagA gene between H. pylori infected asymptomatic volunteers and duodenal ulcer patients (P = 1.0). DNA-DNA hybridization of whole genomic DNA in solution and cluster analysis of rep-PCR genomic DNA fingerprints suggest that isolates from patients with duodenal ulcer disease are different from those obtained from individuals with asymptomatic gastritis. Cluster analysis of the rep-PCR DNA fingerprints revealed two major groups of the strains; one set consisted of strains from patients with duodenal ulcer disease and the second cluster consisted largely of strains from individuals with asymptomatic gastritis. Recent molecular studies suggest that disease-specific cell lineages or strains may exist among H. pylori isolates leading to the various outcomes observed in patients with H. pylori infection.

DNA Fingerprinting↗
PubMed1994

Are there susceptible hosts to Helicobacter pylori infection?

Susceptibility to Helicobacter pylori infection may manifest itself as an increased prevalence of H. pylori infection, as reinfection after eradication, or as different clinical outcomes (gastritis, peptic ulcer disease, primary gastric B-cell lymphoma, or gastric cancer). These outcomes are likely to be a result of interaction between environmental and genetic factors. Genetic factors include both host genetic predisposition to infection as well as genetic differences in H. pylori strains. Twin studies indicate that the correlation coefficient for the relative importance of genetic effects (heritability) on acquisition of H. pylori infection is approximately 0.66. The remaining variance is accounted for by shared rearing environmental factors (20%), and non-shared environmental factors (23%), which contribute to the differences and not the similarities seen between family members. Molecular epidemiological studies of both the whole bacterial genome and of amplified regions between specific repetitive DNA sequences also suggest that there are disease-specific strains of H. pylori. There are, therefore, many different facets of susceptibility to H. pylori infection.

Adult↗
PubMed1993

Helicobacter pylori infection and exaggerated gastrin release. Effects of inflammation and progastrin processing.

Helicobacter pylori infection is associated with exaggerated gastrin release. We investigated whether this abnormality was due to the bacteria or the immune response. Fasting and meal-stimulated 'total' and amidated gastrin were measured in 10 H. pylori-infected volunteers before eradication therapy, after 2 and 14 days of therapy, and 4 weeks after completion of therapy. The exaggerated meal-stimulated gastrin concentration remained unchanged after 2 days of therapy, although the polymorphonuclear cell infiltrate and H. pylori bacteria were no longer evident. The expected fall in gastrin concentration after 14 days of therapy was associated with a reduction in the density of mucosal mononuclear cells, suggesting exaggerated gastrin release was related to chronic inflammation or to H. pylori or its products. The effect of H. pylori on normal progastrin processing was also assessed; 2 control groups were included: 10 H. pylori-uninfected volunteers and 13 patients with H. pylori peptic ulcers. There was a significant difference in the proportion of circulating gastrins that were biologically active amidated gastrins between ulcer patients and uninfected controls (56.7 +/- 4% versus 33.8 +/- 4%, p < 0.001). The proportion of amidated to total gastrins did not increase after successful eradication.

Adult↗
PubMed1993

Gastric mucosal hydrophobicity and Helicobacter pylori: response to antimicrobial therapy.

The hydrophobic properties of the gastric mucosa are reduced by NSAIDs and by Helicobacter pylori infection. Our investigation was to determine whether this abnormality was due to the bacteria or to the inflammatory response. Contact angle measurements were made on gastric antral and corpus biopsies taken from 10 H. pylori-infected volunteers before eradication therapy, after 2 and 14 days of therapy, and 4 weeks after therapy. The contact angle improved steadily and statistically throughout the 2 weeks of therapy (for day 0, 3, 14, respectively) antral mucosa 54.2 +/- 2, 59.3 +/- 2, and 63.2 +/- 2; corpus mucosa 55 +/- 1, 57.8 +/- 3, and 66.6 +/- 1. After 2 days of therapy, H. pylori bacteria were no longer evident, and yet the contact angle continued to improve, suggesting that bacteria and bacterial products (e.g., lipases) may not be critical factors. H. pylori was eradicated in five and failed in five. One month after ending therapy, the contact angles of those with recrudescence of infection and those with eradication were similar and higher (p < 0.05) than before therapy (antrum: 69.8 +/- 1 vs. 71.1 +/- 2, corpus: 66.4 +/- 4 vs. 70.8 +/- 2) (p > 0.25 for both). We conclude that gastric surface hydrophobicity abnormalities do not appear to be directly related to the presence of H. pylori organisms or the histologic features of acute inflammation, but are responsive to antimicrobial therapy.

Adult↗
PubMed1992

Review article: urease, gastric ammonium/ammonia, and Helicobacter pylori--the past, the present, and recommendations for future research.

The presence of ammonium in gastric contents was described in 1852; urease activity in the stomach was identified 70 years later. The discovery of gastric urease resulted in intense research activity to discover its origin, function, and relation to the gastric levels of ammonium and urea. Interest in urease waned in the 1960s as most pertinent questions appeared to have been addressed and there was strong evidence that gastric urease was not a property of the stomach but was of microbial origin. Identification of Helicobacter pylori as the source of urease in the stomach in the last decade has resulted in a rebirth of interest in gastric urease and its products. There is little actual evidence to support a role for toxicity of ammonia in relation to H. pylori and the bulk of the evidence suggests that the products of urease activity are not toxic and may even be beneficial. The purpose of this review is to examine the older literature and to examine new findings in the perspective of what is already known and to suggest areas remaining to be examined. We ask, 'What is old, what is new, and what needs to be done?'

Ammonia↗
PubMed1988

Regulation of intestinal and hepatic apoprotein synthesis after chronic fat and cholesterol feeding.

Although diet influences levels of lipoproteins and their corresponding apoproteins, its effects on the molecular regulation of apoprotein synthesis are relatively unknown. Male Sprague-Dawley rats were fed an atherogenic diet containing cholesterol and propylthiouracil (PTU). Intestinal apo AI and AIV mRNA concentrations were decreased by the atherogenic diet, but apo AI and AIV synthesis was increased in vitro (organ explants) and in vivo (polysome runoff), consistent with regulation at the translational level. In contrast, hepatic apo E mRNA concentration and synthesis were increased after the atherogenic diet, consistent with pretranslational regulation. The response to cholesterol feeding for hepatic apo AI and E showed a third pattern of regulation, in which synthesis increased and mRNA content remained stable or fell, again suggesting translational control, but polysome runoff synthesis was unchanged. The apparent importance of translational regulation in the intestine is consistent with the necessity for the tissue to respond rapidly to changes in intraluminal content.

Animals↗
PubMed1984

Biosynthesis and compartmentalization of rat-intestinal vitamin-D-dependent calcium-binding protein.

We have purified the primary translation product of rat intestinal vitamin-D-dependent calcium-binding protein mRNA from wheat germ and ascites cell-free systems. We show that calcium-binding protein is neither synthesized as a larger percursor nor likely to be exported from the intestinal epithelium. Our conclusions are based on the following observations. (1) The primary translation product, NH2-terminally labeled with formyl[35S]methionine, comigrates with the mature cytoplasmic protein during electrophoresis through denaturing gels. (2) It does not possess a cleavable signal peptide sequence or internal signal equivalent as judged by co- and post-translational cleavage assays in vitro. (3) The NH2 terminus of the cell-free product is acetylated. (4) Comparison of the NH2-terminal amino acid sequences of the primary translation product and cyanogen bromide peptides obtained from the blocked, purified cytoplasmic protein. The kinetics of calcium-binding protein mRNA accumulation and decay in rachitic intestinal epithelium after primary and secondary stimulation with 1,25-dihydroxycholecalciferol (calcitriol) were studied using the cell-free translation system. The results are reminiscent of other steroid-hormone-inducible systems. Both the rate of mRNA accumulation and the peak response were greater after secondary stimulation.

Amino Acid Sequence↗
PubMed1977

Gallium-67 citrate imaging in Hodgkin's disease: final report of cooperative group.

A large cooperative study of Ga-67 uptake in Hodgkin's disease showed that 88% of untreated patients had a positive uptake in one or more lesions. The percent of individual lesions seen on scan, however, was significantly lower; this indicated that negative findings at any one site do not argue strongly against the possiblilty of a lesion there. After treatment, the number of visualized lesions decreased sharply, but the exact role of Ga-67 in evaluating therapy is still not clear. Of the various histologic types of Hodgkin's disease, there was a high incidence of localization in all except the lymphocyte-predominance type, which showed a slightly lower uptake. No lesions less than 1 cm in diameter were successfully imaged and the size most easily detected was 4 cm in diameter. As expected, the imaging technique was much less successful for abdominal lesions than for those at other sites because of interfering concentration in bowel and liver. Both radiotherpy and chemotherapy tend to reverse the abnormalities seen on scan. The finding of a significant number of unsuspected positive lesions in asymptomatic patients returning for routine followup suggests that this is a distinctly valuable use of Ga-67, allowing early therpy for recurrences.

Gallium Radioisotopes↗