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J G Fox

Publications and source records attributed to J G Fox.

At least 55 records · Page 3Linked to original sources
PubMed2000

Synergistic interaction between hypergastrinemia and Helicobacter infection in a mouse model of gastric cancer.

BACKGROUND & AIMS: Hypergastrinemia occurs frequently in association with acid suppression and Helicobacter infection, but its role in the progression to gastric atrophy and gastric cancer has not been well defined. METHODS: The effects of hypergastrinemia, and possible synergy with Helicobacter felis infection, were investigated in insulin-gastrin (INS-GAS) transgenic mice. RESULTS: INS-GAS mice initially showed mild hypergastrinemia, increased maximal gastric acid secretion, and increased parietal cell number but later progressed to decreased parietal cell number and hypochlorhydria. Development of gastric atrophy was associated with increased expression of growth factors, heparin-binding epidermal growth factor and transforming growth factor alpha. At 20 months of age, INS-GAS mice showed no evidence of increased enterochromaffin-like cell number, but instead exhibited gastric metaplasia, dysplasia, carcinoma in situ, and gastric cancer with vascular invasion. Invasive gastric carcinoma was observed in 6 of 8 INS-GAS mice that were >20 months old. Helicobacter felis infection of INS-GAS mice led to accelerated (< or = 8 mo) development of intramucosal carcinoma (85%), with submucosal invasion (54%) and intravascular invasion (46%; P < or = 0.05). CONCLUSIONS: These findings support the unexpected conclusion that chronic hypergastrinemia in mice can synergize with Helicobacter infection and contribute to eventual parietal cell loss and progression to gastric cancer.

Animals↗
PubMed2000

Altered gastrin regulation in mice infected with Helicobacter felis.

Altered gastrin expression associated with Helicobacter pylori infection may contribute to the pathogenesis of peptic ulcer disease or gastric cancer in man, but gastrin has not been investigated in a murine model of Helicobacter infection. C57BL/6 mice were inoculated with Helicobacter felis and examined after 4-21 weeks for G and D cell numbers, antral gastrin and somatostatin mRNA, and luminal pH. In H. felis-infected mice, gastrin mRNA declined at four and six weeks after infection to 57% and 23%, respectively, of uninfected control values. Concurrently, somatostatin mRNA showed no change at four weeks and a modest 25% decrease at six weeks after infection. Similar reductions were noted in G and D cell numbers, resulting in a decrease in the G/D cell ratio after mice were infected with H. felis. Infected animals also showed a loss of parietal and chief cells, and an increased gastric pH. H. felis infection in C57BL/6 mice leads to an early suppression of G cell number and gastrin mRNA. These changes precede an alteration in somatostatin cell number and mRNA and, coupled with reductions in parietal and chief cells, may contribute both to severe impairment of gastric acid output and the potential for carcinogenic processes.

Animals↗
PubMed2000

Concurrent enteric helminth infection modulates inflammation and gastric immune responses and reduces helicobacter-induced gastric atrophy.

Helicobacter pylori is causally associated with gastritis and gastric cancer. Some developing countries with a high prevalence of infection have high gastric cancer rates, whereas in others, these rates are low. The progression of helicobacter-induced gastritis and gastric atrophy mediated by type 1 T-helper cells may be modulated by concurrent parasitic infection. Here, in mice with concurrent helminth infection, helicobacter-associated gastric atrophy was reduced considerably despite chronic inflammation and high helicobacter colonization. This correlated with a substantial reduction in mRNA for cytokines and chemokines associated with a gastric inflammatory response of type 1 T-helper cells. Thus, concurrent enteric helminth infection can attenuate gastric atrophy, a premalignant lesion.

Animals↗
PubMed2000

Identification of enterohepatic Helicobacter species by restriction fragment-length polymorphism analysis of the 16S rRNA gene.

BACKGROUND: Restriction fragment-length polymorphism (RFLP) analysis of a 1,200-bp polymerase chain reaction-amplified DNA fragment of gene coding for 16S rRNA was used to generate restriction profiles of 11 enterohepatic Helicobacter spp. isolated from various animals and humans. METHODS: The amplicon from each Helicobacter sp. was digested with four restriction endonucleases: Alu I, Hinf I, Hha I, and Dde I. Alu I digestion produced five patterns that were useful for initial differentiation. RESULTS: Most Helicobacter spp. isolated from rodents had the same RFLP profiles by Alu I digestion (except H. rodentium and H. cholecystus), but they had different RFLP profiles by Hha I digestion. Only H. bilis and "H. rappini" mouse isolates could not be readily distinguished by the polymerase chain reaction-RFLP method. However, these two species can be distinguished using H. bilis specific primers. Some of the Helicobacter spp. have an intervening sequence in their 16S rRNA gene, which changes the RFLP patterns; in these cases, sequencing is the preferred method to make an appropriate diagnosis. CONCLUSIONS: The RFLP method used in this study was straightforward and rapid and should prove useful as an adjunct for identification and classification of multiple enterohepatic Helicobacter spp.

Animals↗
PubMed2000

Frameshift mutations in rdxA and metronidazole resistance in North American Helicobacter pylori isolates.

In Helicobacter pylori, the oxygen-insensitive nitroreductase RdxA is likely to activate metronidazole (Mtz) by reduction and formation of cytotoxic intermediates. Mutations in rdxA have been associated with Mtz resistance in H. pylori. In vitro Mtz susceptibilities of 17 randomly selected H. pylori isolates were determined by the agar dilution method. DNA sequence analysis of rdxA alleles of eight susceptible isolates (MIC range: 0.25-1.0 mg/L) and nine resistant isolates (MIC range: 16-256 mg/L) showed that six of nine Mtz-resistant H. pylori isolates contained insertion or deletion mutations ('indel' mutations). One isolate contained a substitution mutation at codon position 148 that resulted in the introduction of a premature stop codon. Creation of stop codons within the rdxA coding sequence by either frameshift or substitution mutations resulted in premature translation termination and expression of putatively truncated RdxA polypeptides.

Anti-Bacterial Agents↗
PubMed2000

A new method of post-dialysis blood urea sampling: the 'stop dialysate flow' method.

BACKGROUND: A standardized practical method of post-dialysis blood sampling is required to improve the precision of using urea kinetics in the evaluation of haemodialysis dose and to permit comparative audit. The methods recommended in the Renal Association and Dialysis Outcomes Quality Initiative (DOQI) guidelines reduce the blood pump speed to a low rate at the end of haemodialysis before blood sampling after 10 and 15 s respectively. However, these 'low flow' methods compensate only partially for cardiopulmonary recirculation and may be impractical in routine practice because they involve sequential steps and require accurate timing of sampling. Therefore we have evaluated an alternative method of stopping only the dialysate flow at the end of the haemodialysis session before performing post-dialysis blood sampling. METHODS: The study was performed in three phases. Serial measurements of blood urea were obtained from arterial and venous samples taken at times 0, 30, 60, 120, 180, 240, 300 and 360 s after stopping dialysate flow and leaving the extracorporeal blood flow rate unchanged at the end of the haemodialysis session in 10 patients. A peripheral venous sample was also taken from the contralateral arm at 0 s to reflect body water urea concentration at the end of dialysis without the effect of access recirculation and with a minimal effect of cardiopulmonary recirculation. The same haemodialysis prescription was repeated in the same 10 patients using the Renal Association method to permit comparison between the two methods. The practical use of the 'stop dialysate flow' method was then evaluated in 117 regular haemodialysis patients undergoing routine monthly assessment of dialysis adequacy and compared with sampling immediately post-dialysis. RESULTS: Within 4 min of stopping the dialysate flow there was no difference between the blood urea concentrations of arterial and venous samples, indicating cessation of diffusion across the dialysis membrane. Also the blood urea concentrations in all of the arterial and venous samples between 4 and 6 min were constant and were equivalent to the blood urea concentration of the peripheral venous sample taken at 0 s. These data suggest that post-dialysis blood sampling may be performed 5 min after stopping dialysate flow at the end of the haemodialysis session. In contrast, the blood urea concentration in the post-dialysis samples obtained using the Renal Association method were lower than the contralateral arm blood urea concentration taken at 0 s (0.31+/-0.42; P<0.05) and consequently the percentage URR was higher (1.35+/-1.84%). In 117 patients the post-dialysis blood urea sample 5 min after stopping dialysate flow averaged 5.49+/-2.11 mmol/1 compared with 5.07+/-2.05 mmol/l immediately after the end of the haemodialysis session (P<0. 0001). This was equivalent to a reduction in URR from 71.7+/-8.3% with sampling immediately post-dialysis to 69.1+/-9.3% with the 'stop dialysate flow' method. CONCLUSIONS: This study shows that there is a window period between 4 and 6 min after stopping dialysate flow at the end of the haemodialysis session when the blood urea concentration in a sample taken from any part of the extracorporeal circuit remains constantly within the co-efficient of variation of laboratory measurement, and is equivalent to a peripheral venous sample taken immediately at the end of the dialysis session. A 'stop dialysate flow' method with blood sampling after 5 min offers several advantages over 'slow flow' methods, since it allows for cardiopulmonary as well as access recirculation, does not require precise timing of blood sampling, and is simple to perform in a busy renal unit. For these reasons the 'stop dialysate flow' method may be used for routine monitoring of the adequacy of delivered haemodialysis and for comparative audit among haemodialysis centres.

Adult↗
PubMed2000

'Flexispira rappini' strains represent at least 10 Helicobacter taxa.

'Flexispira rappini' is a provisional name given to gram-negative, microaerophilic, motile, spindle-shaped micro-organisms with spiral periplasmic fibres and bipolar tufts of sheathed flagella. Several investigators, including Kirkbride, Romero, and Archer isolated strains possessing this morphology. Previously, the phylogenetic position of three 'Flexispira rappini' strains was determined by 165 rRNA sequencing, which indicated that flexispira were members of the genus Helicobacter. As more organisms with 'F. rappini' morphology were isolated, it became apparent that there were multiple Helicobacter taxa with this distinctive morphology. The purpose of this study was to examine a collection of 36 'F. rappini' strains from diverse habitats by using 165 rRNA sequence analysis. The strains fell into 10 taxa, each possibly representing a novel Helicobacter species. Two of these flexispira taxa were previously named, by us, Helicobacter bilis and Helicobacter trogontum. Currently, none of the flexispira taxa contains enough phenotypically and genotypically characterized strains to be formally named 'Helicobacter rappinii'.

Animals↗
PubMed2000

Recommended minimal standards for describing new species of the genus Helicobacter.

The International Committee of Systematic Bacteriology Subcommittee on the taxonomy of Campylobacter and related bacteria has agreed in principle on minimum requirements for the description of new species of the genus Helicobacter. These requirements include the recommendation that the description of a putative new species or subspecies be based on examination of at least five strains in order to provide a measure of phenotypic and genotypic variation. Recommendations for required phenotypic and molecular data are presented. The requirements are consistent with the polyphasic approach to bacterial systematics.

Animals↗
PubMed2000

Isolation and characterization of a Helicobacter sp. from the gastric mucosa of dolphins, Lagenorhynchus acutus and Delphinus delphis.

Gastric ulcerations in dolphins have been reported for decades. Some of these lesions were associated with parasitic infections. However, cases of nonparasitic gastric ulcers with no clearly defined etiology also have been reported in wild and captive dolphins. Considerable speculation exists as to whether dolphins have Helicobacter-associated gastritis and peptic ulcer disease. The stomachs of seven stranded Atlantic white-sided dolphins, Lagenorhynchus acutus, and 1 common dolphin, Delphinus delphis, were assessed for the presence of Helicobacter species. Novel Helicobacter species were identified by culture in the gastric mucosa of two of the eight dolphins studied and by PCR in seven of the eight dolphins. The gram-negative organisms were urease, catalase, and oxidase positive. Spiral to fusiform bacteria were detected in gastric mucosa by Warthin Starry staining. Histopathology revealed mild to moderate diffuse lymphoplasmacytic gastritis within the superficial mucosa of the main stomach. The pyloric stomach was less inflamed, and bacteria did not extend deep into the glands. The lesions parallel those observed in Helicobacter pylori-infected humans. Bacteria from two dolphins classified by 16S rRNA analysis clustered with gastric helicobacters and represent a novel Helicobacter sp. most closely related to H. pylori. These findings suggest that a novel Helicobacter sp. may play a role in the etiopathogenesis of gastritis and gastric ulcers in dolphins. To our knowledge this represents the first isolation and characterization of a novel Helicobacter sp. from a marine mammal and emphasizes the wide host distribution and pathogenic potential of this increasingly important genus.

Animals↗
PubMed2000

Chronic atrophic gastritis in SCID mice experimentally infected with Campylobacter fetus.

Campylobacter fetus is a cause of enteritis and invasive extraintestinal disease in humans. In order to develop an animal model of C. fetus infection, outbred ICR SCID mice were orally challenged with a clinical isolate of C. fetus. The stomachs of SCID mice were heavily colonized with C. fetus, and colonization was associated with the development of chronic atrophic gastritis. This lesion was characterized by an inflammatory infiltrate of granulocytes and macrophages that over time resulted in a loss of specialized parietal and chief cells in the corpus and the appearance of a metaplastic mucous epithelium. This lesion bears similarity to that encountered during experimental murine infection with Helicobacter pylori or Helicobacter felis. Despite colonization of the cecum and colon tissues by C. fetus in SCID mice, no lesions were noted in these tissues. A follow-up study confirmed these findings for SCID mice and also demonstrated that C. fetus could also infect the gastric mucosa of wild-type, outbred ICR mice. However, in ICR mice, the anatomic extent of colonization was more limited and the severity of inflammation and epithelial alterations was significantly less than that observed in infected SCID mice. The stomach may represent an unrecognized environmental niche for Campylobacter species.

Animals↗
PubMed2000

Helicobacter aurati sp. nov., a urease-positive Helicobacter species cultured from gastrointestinal tissues of Syrian hamsters.

A novel helicobacter with the proposed name Helicobacter aurati (type strain MIT 97-5075c) has been isolated from the inflamed stomachs and ceca of adult Syrian hamsters. The new species is fusiform with multiple bipolar sheathed flagella and periplasmic fibers; it contains urease and gamma-glutamyl transpeptidase. By 16S rRNA sequencing and repetitive element PCR-based DNA fingerprinting, it was found that H. aurati represents a distinct taxon and clusters with Helicobacter muridarum, Helicobacter hepaticus, and Helicobacter sp. MIT 94-022. H. aurati was recovered from hamsters housed in various research and vendor facilities. Further studies are necessary to define its association with disease and other microbiota in hamsters, as well as its impact on research projects involving hamsters. H. aurati (GenBank accession number AF297868) can be used in animal experiments to define the factors that are important for gastric helicobacter pathogenesis.

Animals↗
PubMed2000

Helicobacter canadensis sp. nov. isolated from humans with diarrhea as an example of an emerging pathogen.

We recently analyzed 11 helicobacter isolates cultured from diarrhea patients in Canada. These isolates had been characterized biochemically by restriction fragment length polymorphism (RFLP; AluI, HhaI) analysis and by fatty-acid analysis as Helicobacter pullorum. However, four of the isolates differed biochemically from H. pullorum by their inability to hydrolyze indoxyl acetate and their resistance to nalidixic acid. Using complete 16S rRNA analysis, we determined that these four strains clustered near H. pullorum but had a sequence difference of 2% and therefore represent a novel helicobacter, Helicobacter canadensis. This novel helicobacter could also be distinguished from H. pullorum by RFLP analysis using ApaLI. The number of novel Helicobacter spp. associated with gastrointestinal disease in humans and animals is rapidly increasing. There are now six Helicobacter spp. isolated from diarrheic humans, the other five being H. pullorum, H. canis, "H. rappini," H. fennelliae, and H. cinaedi. This finding highlights the importance of careful molecular analysis in addition to standard biochemical tests in identifying the increasing number of Helicobacter spp. isolated from humans and animals.

Bacterial Typing Techniques↗
PubMed2000

C-cell carcinoma (medullary thyroid carcinoma) associated with multiple endocrine neoplasms in a ferret (Mustela putorius).

A firm, infiltrative mass was found in the thyroid region of an adult castrated male ferret (Mustela putorius) presenting with vague signs of weight loss, minor inappetence, and decreased activity. Efforts to surgically excise the tissue were unsuccessful, and the animal was euthanatized. Gross and histopathologic evaluation revealed multiple endocrine neoplasms, including C-cell carcinoma, adrenocortical adenoma, pheochromocytoma, and endocrine tumor of the pancreas. This is the first descriptive account of a C-cell carcinoma, also known as medullary thyroid carcinoma, in a ferret, although other endocrine neoplasms in this species have been reported with some frequency. These findings mimic features observed in human multiple endocrine neoplasia syndromes.

Animals↗
PubMed2000

Gastritis and intestinal metaplasia in Syrian hamsters infected with Helicobacter aurati and two other microaerobes.

Chronic gastritis and intestinal metaplasia associated with naturally occurring colonization by Helicobacter aurati and two other microaerobic species were observed in Syrian hamsters. Thirty-five hamsters, between 7 and 12 months of age, were evaluated from two research and three commercial facilities. Microaerobic bacteria were cultured from the hamster stomachs. These bacteria included H. aurati, a fusiform, urease-positive species; a second novel helical, urease-negative Helicobacter sp.; as well as a smaller, urease-negative Campylobacter sp. Southern blot analysis detected Helicobacter spp. DNA in the gastric tissues of all 35 hamsters; 15 hamsters also had Campylobacter sp. DNA in their gastric tissues. When examined by light microscopy, argyrophilic bacteria consistent with H. aurati or the second Helicobacter sp. were present in antral sections of 12 out of the 15 hamsters where bacteria were seen, while 9 out of the 15 hamsters had bacteria resembling the Campylobacter sp. The presence of Helicobacter spp. but not the presence of Campylobacter sp. was significantly correlated to gastritis severity (P < 0.0001 for Helicobacter spp., P = 0.6025 for Campylobacter sp.) and intestinal metaplasia, as measured by numbers of goblet cells (P = 0.0239 for Helicobacter spp., P = 0.5525 for Campylobacter sp.). Severely affected hamsters also had Giardia sp. within their metaplastic gastric pits. Hamsters with naturally occurring helicobacter-associated gastritis provide a model for studying the development of intestinal metaplasia and gastric giardiasis in H. pylori-infected humans.

Animals↗
PubMed2000

Monitoring sentinel mice for Helicobacter hepaticus, H rodentium, and H bilis infection by use of polymerase chain reaction analysis and serologic testing.

BACKGROUND AND PURPOSE: Natural infection of research mice with enterohepatic Helicobacter spp. is common and may confound experimental studies from intercurrent disease. We evaluated a protocol of dirty bedding exposure for transmission of Helicobacter infection from colony mice to female Tac:(SW)fBR sentinel mice over 6 months. METHODS: Cecal scrapings from culled colony mice and associated sentinel mice were tested for H. hepaticus, H. rodentium, and H. bilis using polymerase chain reaction analysis (PCR). These results were correlated with the results of sentinel serum IgG responses measured by ELISA. RESULTS: In 9 colony rooms, 43 of 45 mice were infected with H. hepaticus; in 14 rooms, 58 of 70 mice were infected with H. rodentium; and in 2 rooms, 2 of 10 mice were infected with H. bilis. Concurrence of Helicobacter infection between colony and sentinel mice was 82% for H. hepaticus, 88% for H. rodentium, and 94% for H. bilis. Concurrence of Helicobacter infection status of sentinel cagemates was 98% for H. hepaticus, 86% for H. rodentium, and 95% for H. bilis. Fecal samples pooled by sentinel cage had positive PCR results for H. hepaticus and H. rodentium at 1 month in 60 and 44%, respectively, of the cages that contained test-positive mice at necropsy (6 months). By 3 months, detection rates were 100 and 81% for H. hepaticus and H. rodentium, respectively, and H. bilis was not detected until 4 months. Newly acquired infections with H. rodentium and H. bilis were evident throughout the 6-month study period. Seroconversion was coincident with positive PCR results in sentinel mice, and serum IgG values continued to increase until necropsy. The serum IgG ELISA was 98 to 100% sensitive, but was low in specificity (34 to 44%), most likely attributable to common coinfection with H. hepaticus and H. rodentium. CONCLUSION: Sentinel mice acquire infection with Helicobacter spp. through dirty bedding exposure. Combined use of PCR analysis and serologic testing of sentinel mice was predictive of Helicobacter infection status of mouse colonies used for biomedical research.

Animals↗
PubMed2000

Neuropathology of bouncer Long Evans, a novel dysmyelinated rat.

BACKGROUND AND PURPOSE: Spontaneous animal mutants affected by abnormal formation of myelin in the central nervous system (CNS) are useful in studies on myelinogenesis and remyelination leading to better understanding of cellular and molecular interactions involved in myelin repair. A novel rat mutant, Bouncer Long Evans (LE-bo) is severely dysmyelinated, but with exceptional longevity, and its clinical and pathologic phenotype are described. METHODS: Clinical observations, genetic studies, and determination of longevity were performed in a colony of rats, including carriers of LE-bo phenotype producing the mutant animals. Comprehensive histologic studies were performed on all perfusion-fixed tissues, and ultrastructural examination of the optic nerve and thoracic part of the spinal cord also was done in rats 1 to 14 weeks old. RESULTS: The LE-bo phenotype is characterized by whole body tremor, progressively severe ataxia, and severe seizure activity. The LE-bo phenotype is transferred as an autosomal recessive trait and is stable. The LE-bo rat can survive in good health beyond 45 weeks. Neuropathologic changes include severe global dysmyelination, with thin uncompacted myelin sheaths in young rats forming no major dense line, whereas the myelin sheaths of the peripheral nervous system appear normal. Oligodendrocytes degenerate with apparently progressing accumulation of membranous material in the perikaryon. Large numbers of immature glial cells were detected in the CNS of LE-bo rats at 4 to 14 weeks. CONCLUSION: The LE-bo rat is severely dysmyelinated due to inability of its oligodendrocytes to form myelin sheaths. Similarities of the LE-bo rat and Long Evans Shaker (les) rat neuropathologic features, such as severe dysmyelination, lack of major dense line in uncompacted myelin sheaths, apparent proliferation of oligodendroglial cells, and considerable longevity, are striking and suggest that a LE-bo mutation may functionally affect the myelin basic protein gene.

Animals↗