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Biomedical subjects

J G Fox

Publications and source records attributed to J G Fox.

At least 19 recordsLinked to original sources
PubMed2006

Rapid onset of ulcerative typhlocolitis in B6.129P2-IL10tm1Cgn (IL-10-/-) mice infected with Helicobacter trogontum is associated with decreased colonization by altered Schaedler's flora.

Infection with Helicobacter trogontum, a urease-positive helicobacter isolated from subclinically infected rats, was evaluated in B6.129P2-IL10(tm1Cgn) (interleukin-10(-/-) [IL-10(-/-)]) and C57BL/6 (B6) mice. In a first experiment, IL-10(-/-) mice naturally infected with Helicobacter rodentium had subclinical typhlocolitis but developed severe diarrhea and loss of body condition with erosive to ulcerative typhlocolitis within 1 to 3 weeks of experimental infection with H. trogontum. A second experiment demonstrated that helicobacter-free IL-10(-/-) mice dosed with H. trogontum also developed severe clinical signs and typhlocolitis within 2 to 4 weeks, whereas B6 mice colonized with H. trogontum were resistant to disease. In a third experiment, using helicobacter-free IL-10(-/-) mice, dosing with H. trogontum resulted in acute morbidity and typhlocolitis within 8 days. Acute typhlocolitis was accompanied by signs of sepsis supported by degenerative hemograms and recovery of Escherichia coli and Proteus spp. from the livers of infected mice. Quantitative PCR data revealed that H. rodentium and H. trogontum may compete for colonization of the lower bowel, as H. trogontum established higher colonization levels in the absence of H. rodentium (P < 0.003). H. trogontum-induced typhlocolitis was also associated with a significant decrease in the levels of colonization by five of eight anaerobes that comprise altered Schaedler's flora (P < 0.002). These results demonstrate for the first time that H. rodentium infection in IL-10(-/-) mice causes subclinical typhlocolitis and that infection with H. trogontum (with or without H. rodentium) induces a rapid-onset, erosive to ulcerative typhlocolitis which impacts the normal anaerobic flora of the colon and increases the risk of sepsis.

Animals↗
PubMed2006

Progressive proliferative and dysplastic typhlocolitis in aging syrian hamsters naturally infected with Helicobacter spp.: a spontaneous model of inflammatory bowel disease.

Helicobacter spp. have been implicated in a variety of gastrointestinal tract diseases, including peptic ulcer disease, gastric cancer, and inflammatory bowel disease (IBD), in humans and animals. Although most models of IBD are experimentally induced, spontaneous or natural models of IBD are rare. Herein, we describe a long-term study of chronic, progressive lesions that develop in the distal portion of the large bowel of unmanipulated Syrian hamsters naturally infected with Helicobacter spp. Twenty-four Syrian hamsters of three age groups (group A, 1 month [n = 4], group B, 7-12 months [n = 12], group C, 18-24 months [n = 12]), underwent complete postmortem examination. Results of microbial isolation and polymerase chain reaction and restriction fragment length polymorphism analyses confirmed the presence of Helicobacter spp. infection in the distal portion of the large bowel of all animals. Additionally, confounding pathogens, such as Clostridium difficile, Lawsonia intracellularis, and Giardia spp. that can cause proliferative enteritis, were absent in the hamsters of this study. Histopathologic scores for inflammation (P < 0.01), hyperplasia (P < 0.01), and dysplasia (P < 0.05) were significantly higher in the ileocecocolic (ICC) junction of animals in group C, relative to group A. Dysplastic lesions of various grades were detected in 5 of 11 hamsters in group C. Interestingly, the segment of the bowel that is usually colonized by Helicobacter spp. in hamsters had the most severe lesions. One hamster of group C developed a malignant fibrous histiocytoma, whereas another hamster developed a round cell sarcoma originating from the ICC junction. Thus, lesions in the distal portion of the large bowel of aging hamsters naturally colonized with Helicobacter spp. warrants developing the hamster as an animal model of IBD and potentially IBD-related cancer.

Animals↗
PubMed2006

Clostridium piliforme infection in two farm-raised white-tailed deer fawns (Odocoileus virginianus) and association with copper toxicosis.

Necropsy of 2 white-tailed deer fawns who died acutely revealed diarrhea and melena in case No. 1 and no gross changes in case No. 2. Histologically, the livers of both deer displayed multifocal coagulative necrosis, with infiltrations of neutrophils, macrophages, and lymphocytes. By Warthin-Starry staining, bundles of filamentous bacteria were identified within hepatocytes at the periphery of the necrotic foci in case No. 1. There was multifocal myocardiocyte necrosis in case No. 1 and multifocal lymphoid necrosis of the Peyer's patches in case No. 2. Clostridium piliforme 16S ribosomal ribonucleic acid gene was detected in both livers by polymerase chain reaction (PCR) with C. piliforme-specific primers. The liver copper levels in both cases were normal to slightly elevated. The kidney copper level in case No. 2 was elevated. This represents the first published cases of Tyzzer's disease in deer, a novel use of PCR for the diagnosis of C. piliforme infection, and a possible association between copper toxicosis and Tyzzer's disease.

Animal Diseases↗
PubMed2006

Acute renal cortical necrosis in a series of young men with severe acute pancreatitis.

Diffuse renal cortical necrosis from any cause is rare in the Western World. Over the last 5 decades, there have been isolated case reports of acute cortical necrosis as a consequence of acute pancreatitis, but the long-term outcome of these patients has not previously been reported. Here, we report 3 young men, aged 16-21 years, who have presented over the past 19 years with severe acute pancreatitis associated with oliguric acute renal failure. They were all found to have diffuse renal cortical necrosis and consequently made no renal recovery. Despite the appreciable mortality associated with acute pancreatitis complicated by acute renal failure, they all survived the initial illness and all have successfully undergone renal transplantation. We present a detailed account of each patient including diagnostic strategies and discuss the possible factors contributing to a favorable outcome in these patients.

Acute Disease↗
PubMed2005

Pharmacy-implemented guidelines on switching from intravenous to oral antibiotics: an intervention study.

BACKGROUND: A high proportion of medical in-patients in the UK receive intravenous (IV) antibiotic therapy. This may be inappropriate in non-severe infections, or unnecessarily prolonged. AIM: To assess the impact of guideline implementation on IV antibiotic prescribing in medical admissions to a general hospital. DESIGN: Observational intervention study. METHODS: Data relating to infection and antibiotic therapy were collected for 4 weeks pre-intervention (group 1) and 4 weeks post intervention (group 2). Six months later, data were collected for a further 4 weeks following a second intervention (group 3). Interventions consisted of pharmacy-led implementation of guidelines incorporating criteria for IV therapy and switching to the oral route. The second intervention also included pharmacy-initiated feedback on prescribing. The main outcome measures were IV antibiotic duration, and appropriateness of the IV route and switching. RESULTS: Of 2365 admissions, 757 (32%) had 806 treated episodes. IV therapy was used in 40%, 46% and 36% (groups 1, 2 and 3, respectively) and was appropriate in 92% vs. 100% (group 1 vs. 2). In groups 2 and 3, oral switch timing was appropriate in 90% and 88%, vs. 17% in group 1 (p < 0.001). Between groups 1 and 2, median duration of IV therapy was reduced from 3 to 2 days (p = 0.01). More patients in group 2 received appropriate exclusively IV therapy (65% vs. 96%, p < 0.01). Duration of stay in IV-treated patients reduced from 13 to 10 days in groups 2 and 3 (p = 0.047). IV antibiotic expenditure reduced by 13% per patient admitted between groups 1 and 2. DISCUSSION: Pharmacy-led introduction of antibiotic guidelines appears to result in clinically appropriate reductions in IV therapy.

Administration, Oral↗
PubMed2005

Gastritis-associated adenocarcinoma and intestinal metaplasia in a Syrian hamster naturally infected with Helicobacter species.

The objective of this study was to evaluate stomachs of 2-year-old Syrian hamsters that were naturally colonized by multiple Helicobacter species including Helicobacter aurati. A previous report on 7- to 12-month-old Syrian hamsters described chronic gastritis and intestinal metaplasia, a putative preneoplastic lesion in the stomach, without cancer. This report describes an invasive adenocarcinoma at the pyloric-duodenal junction in one of nine hamsters at a site of helicobacter-associated inflammation and marked intestinal metaplasia. Ceca of nine of nine animals were culture positive and polymerase chain reaction positive for Helicobacter spp. Furthermore, immunohistochemical analysis of the stomach using a H. pylori polyclonal antibody detected positive-staining bacteria within the pyloric region of three of nine hamsters including the neoplastic glands. However, argyrophilic bacteria were demonstrated only within the stomach of the hamster with gastric adenocarcinoma. This is a first report of gastric adenocarcinoma in helicobacter-infected hamsters. Syrian hamsters appear suitable as potential model for studying development of helicobacter-associated gastric adenocarcinomas.

Adenocarcinoma↗
PubMed2005

The link between circulating markers of endothelial function and proteinuria in patients with primary glomerulonephritis.

INTRODUCTION: It is well established that there is an increase in the incidence of cardiovascular mortality in patients with proteinuric renal disease. The magnitude of the increase in risk is unlikely to be explained by traditional risk factors for cardiovascular disease alone. Proteinuria itself may constitute an additional risk factor, and proteinuric patients are known to have a degree of endothelial dysfunction. The nature of this relationship between proteinuria and endothelial function is the subject of intense investigation. AIM: The aim of this study was to examine the relationship between proteinuria and endothelial dysfunction, as reflected by serum von Willebrand factor (vWF), and the soluble cell adhesion molecules VCAM and ICAM, in patients with primary glomerulonephritis (GN). A secondary aim was to discern whether any relationship could be explained by renal function, lipid profile, inflammation or blood pressure. METHODS: A cross-sectional study was undertaken in consecutive patients attending a general nephrology clinic with biopsy-proven primary GN. Patients with end-stage renal disease (ESRD), those on immunosuppressive drugs, or with intercurrent infective illnesses were excluded. Blood pressure and body mass index were recorded. Routine lab assays were undertaken for serum creatinine, lipid profile, and 24-hour urinary protein (U(Prot)). Additional serum samples were stored at -80 degrees C for subsequent measurement of vWF, VCAM, ICAM and sensitive C reactive protein (sCRP). RESULTS: Data were collected from 129 (86 male) patients. Mean (standard deviation) estimated creatinine clearance was 64 (32) ml/min, and median (interquartile range) 24-hour proteinuria was 1.1 (0.22-2.9) g. Mean vWF was 173 (68) IU/dl, median VCAM, ICAM and sCRP were 594 (410-708) ng/ml, 235 (208-286) ng/ml, and 2.33 (0.83-5.68) mg/l, respectively. There was a significant positive correlation between vWF and U(Prot) (Spearman rank correlation, r = 0.41, p < 0.001). When split into tertiles, according to U(Prot) (0-500 mg, 500-2000 mg, and > 2000 mg), there was a significant, stepwise increase in mean vWF (p < 0.001), log VCAM (p < 0.001), and log ICAM (p = 0.002). On multivariate analysis with vWF as the continuous dependent variable, U(Prot), age, total cholesterol and sCRP were the only significantly independent correlates (model-adjusted R2 = 33%). CONCLUSION: In patients with primary GN, there is a significant association between endothelial activation as reflected by vWF, VCAM, or ICAM and increasing proteinuria. Elevations in vWF, as well as being related to classical risk factors, are associated with increases in total proteinuria and low-grade inflammation. Thus, future prospective studies should examine the extent to which vWF and other circulating markers of endothelial activation predict coronary heart disease risk in patients with proteinuric renal disease.

Adult↗
PubMed2003

Failure of surface ring mutant strains of Helicobacter mustelae to persistently infect the ferret stomach.

Helicobacter mustelae, the gastric pathogen of ferrets, produces an array of surface ring structures which have not been described for any other member of the genus Helicobacter, including H. pylori. The unique ring structures are composed of a protein named Hsr. To investigate whether the Hsr rings are important for colonization of the ferret stomach, ferrets specific pathogen free for H. mustelae were inoculated with an Hsr-deficient mutant strain or the wild-type H. mustelae strain. Quantitative cultures from antral biopsy specimens obtained at 3, 6, and 9 weeks postinoculation demonstrated no significant difference in the levels of bacteria in the ferrets that received the Hsr-negative strain and the ferrets infected with the parent strain. However, when the ferrets were biopsied at 12 and 15 weeks and necropsied at 18 weeks after infection, the levels of bacteria of the Hsr-negative strain in the stomach antrum were significantly reduced. This decline contrasted the robust antral colonization by the wild-type strain. The Hsr-negative strain did not efficiently colonize the gastric body of the study ferrets. Histological examination at 18 weeks postinoculation revealed minimal gastric inflammation in the animals that received the mutant H. mustelae strain, a finding consistent with its waning infection status, whereas lesions characteristic of helicobacter infection were present in ferrets infected with the wild-type strain. Scant colonization by the Hsr-negative H. mustelae strain at the end of the 18-week study, despite initial successful colonization, indicates an inability of the mutant to persist, perhaps due to a specific host response.

Animals↗
PubMed2003

Urinary transferrin, high molecular weight proteinuria and the progression of renal disease.

AIMS: Proteinuria predicts rate of progression in a variety of nephropathies. There is considerable evidence that iron-transferrin is toxic to proximal tubular cells in vitro, and recent clinical work suggests that selectivity of proteinuria influences the outcome of renal disease. The aim of this study was to examine the relationship between the nature of proteinuria and progression of renal disease. METHODS: This was a prospective, cross-sectional study in 66 patients with primary glomerulonephritis, diabetic nephropathy and a variety of other renal diseases. Urinary transferrin was measured by sandwich ELISA and correlated with rate of change in estimated creatinine clearance (ECC). Urinary SDS-PAGE was undertaken to divide proteinuria into tertiles according to molecular weight and to quantify the protein in each tertile. The magnitude of each tertile was then correlated with rate of change in ECC over a median period of 20 months. RESULTS: Rate of change of renal function correlated with total proteinuria (r2 = 18%, p < 0.001) and albuminuria (r2 = 17%, p < 0.001), but not urinary transferrin (r2 = 0%, p = 0.235). On univariate analysis high molecular weight proteinuria (r2 = 21%, p < 0.001), intermediate molecular weight proteinuria (r2 = 15%, p = 0.001) and low molecular weight proteinuria (r2 = 10%, p = 0.005) correlated with rate of change in ECC as did total fasting cholesterol (r2 = 7%, p = 0.003). On multivariate analysis, however, the only independent predictors of rate of change in ECC were high molecular weight proteinuria (r2 = 19%, p < 0.001), and total fasting cholesterol (r2 = 5%, p = 0.035). CONCLUSIONS: We found no evidence to support the hypothesis that iron-transferrin is important in the development of human renal injury. High molecular weight proteinuria correlates more strongly with rate of progression of renal disease than intermediate molecular weight, low molecular weight or even total proteinuria. This suggests either, that one or more high molecular weightproteins are implicated in causing progressive renal impairment, or that loss of size selectivity at the glomerular basement membrane is associated with accelerated tubulointerstitial damage.

Adult↗
PubMed2002

Isolation of differentially expressed genes from white spot virus (WSV) infected Pacific blue shrimp (Penaeus stylirostris).

To isolate novel cellular factors that are activated or repressed upon WSV infection, the RNA fingerprints of healthy and WSV infected blue shrimp ( Penaeus stylirostris) were compared using the mRNA differential display technique. Thirty-two unique differentially expressed, and one constitutively expressed, cDNA sequences were retrieved. Six of 32 cDNAs showed similarities with the database entries: cDNA 10G32-142 to a shrimp arginine kinase, 22C48-201 to shrimp mitochondrial ATPase gene; 22C47-197, 21G49-203 and 20A55-268 to shrimp ESTs and 20G50-206 to a WSV gene, ORF 116. The constitutively expressed gene showed significant similarity to a yeast elongation factor 1-alpha gene. The expression of a subset of differentially expressed genes (13 of 32) was further evaluated by real-time RT-PCR. Ten of 13 genes showed statistically significant changes in expression between healthy and WSV infected animals suggesting that these genes may play an important role in WSV pathogenesis.

Amino Acid Sequence↗
PubMed2002

Helicobacter cetorum sp. nov., a urease-positive Helicobacter species isolated from dolphins and whales.

A novel helicobacter with the proposed name Helicobacter cetorum, sp. nov. (type strain MIT 99-5656; GenBank accession number AF 292378), was cultured from the main stomach of two wild, stranded Atlantic white-sided dolphins (Lagenorhynchus acutus) and from the feces of three captive cetaceans (a Pacific white-sided dolphin [Lagenorhynchus obliquidens]; an Atlantic bottlenose dolphin [Tursiops truncatus]; and a beluga whale [Delphinapterus leucas]). The infected captive cetaceans were either subclinical, or clinical signs included intermittent regurgitation, inappetance, weight loss, and lethargy. Ulcers were observed in the esophagus and forestomach during endoscopic examination in two of the three captive animals. In the third animal, esophageal linear erosions were visualized endoscopically, and histopathological evaluation of the main stomach revealed multifocal lymphoplasmacytic gastritis with silver-stained spiral-shaped bacteria. Helicobacter cetorum is a fusiform gram-negative bacterium with a single bipolar flagellum. The isolates grow under microaerobic conditions at 37 and 42 degrees C but not at 25 degrees C. H. cetorum is urease, catalase, and oxidase positive, and it is sensitive to cephalothin. The isolates from the wild, stranded dolphins were sensitive to nalidixic acid, whereas the isolates from the collection animals were resistant. By 16S rRNA sequencing it was determined that H. cetorum represented a distinct taxon that clusters most closely with H. pylori. Further studies are necessary to determine the role of H. cetorum in the development of gastric ulcers and gastritis of cetaceans. This is the first description and formal naming of a novel Helicobacter species from a marine mammal.

Animals↗
PubMed2002

Molecular evidence of Helicobacter cinaedi organisms in human gastric biopsy specimens.

One hundred twenty-six urease-negative gastric biopsy specimens were evaluated for the presence of Helicobacter genus-specific 16S ribosomal DNA (rDNA) and H. pylori-specific glmM DNA sequences by PCR. The species specificity of the glmM PCR assay was demonstrated, as H. pylori was the only Helicobacter species that yielded the expected glmM amplicon. Most urease-negative specimens (118 of 126 specimens) lacked Helicobacter DNA. However, 8 of 126 urease-negative specimens contained Helicobacter 16S rDNA. In order to identify the Helicobacter species present in urease-negative gastric biopsy specimens, 16S rDNA amplicons were cloned and sequenced. Sequence comparisons were performed by analyses of the sequences in public sequence databases. Two samples contained 16S rDNA that was identified as H. cinaedi with 100% identity and that spanned approximately 400 bp (398 and 398 bp, respectively). In contrast, multiple differences (97% identity; 390 of 398 bp) were observed with H. pylori 16S rDNA in this region. This finding was verified by sequencing an overlapping 537-bp fragment within the 5' portion of 16S rDNA. Although the clinical findings were consistent with H. pylori infection (e.g., duodenal ulcer disease), rapid urease testing and DNA sequence analyses suggested the presence of H. cinaedi organisms and the absence of H. pylori in two human antral biopsy specimens. This study represents the first report of an enteric urease-negative helicobacter in the human stomach. Although these organisms were previously associated with extragastric infections, the roles of these organisms in the pathogenesis of chronic gastritis or peptic ulcer disease remain unclear.

Base Sequence↗
PubMed2002

The non-H pylori helicobacters: their expanding role in gastrointestinal and systemic diseases.

The number of species in the genus Helicobacter has rapidly expanded over the past decade. The genus now includes at least 24 formally named species as well as numerous other helicobacters awaiting formal naming. This review highlights the expanding role that other helicobacters, although not as well known as H pylori, play in gastrointestinal and systemic disease in humans.

Arthritis, Infectious↗
PubMed2002

Hepatobiliary inflammation, neoplasia, and argyrophilic bacteria in a ferret colony.

Hepatobiliary disease was diagnosed in eight of 34 genetically unrelated cohabitating pet ferrets (Mustela putorios furo) during a 7-year period. The eight ferrets ranged in age from 5 to 8 years and exhibited chronic cholangiohepatitis coupled with cellular proliferation ranging from hyperplasia to frank neoplasia. Spiral-shaped argyrophilic bacteria were demonstrated in livers of three ferrets, including two with carcinoma. Sequence analysis of a 400-base pair polymerase chain reaction product amplified from DNA derived from fecal bacteria from one ferret demonstrated 98% and 97% similarity to Helicobacter cholecystus and Helicobacter sp. strain 266-1 , respectively. The clustering of severe hepatic disease in these cohabitating ferroes suggests a possible infectious etiology. The role of Helicobacter species and other bacteria in hepatitis and/or neoplasia in ferrets requires further study.

Animals↗
PubMed2001

Recombination and mutation during long-term gastric colonization by Helicobacter pylori: estimates of clock rates, recombination size, and minimal age.

The bacterium Helicobacter pylori colonizes the gastric mucosa of half of the human population, resulting in chronic gastritis, ulcers, and cancer. We sequenced ten gene fragments from pairs of strains isolated sequentially at a mean interval of 1.8 years from 26 individuals. Several isolates had acquired small mosaic segments from other H. pylori or point mutations. The maximal mutation rate, the import size, and the frequency of recombination were calculated by using a Bayesian model. The calculations indicate that the last common ancestor of H. pylori existed at least 2,500-11,000 years ago. Imported mosaics have a median size of 417 bp, much smaller than for other bacteria, and recombination occurs frequently (60 imports spanning 25,000 bp per genome per year). Thus, the panmictic population structure of H. pylori results from very frequent recombination during mixed colonization by unrelated strains.

Bayes Theorem↗
PubMed2001

Genomic characterization of Helicobacter hepaticus: ordered cosmid library and comparative sequence analysis.

Helicobacter hepaticus is an important pathogen in laboratory mice and induces the development of liver tumors and gastrointestinal disease in susceptible strains of mice. In this study, a miniset of 36 cosmid clones from a genomic library of H. hepaticus was ordered and grouped into four large contigs representing approximately 1 Mb of the H. hepaticus genome using PCR, DNA sequencing, Southern and dot-blot hybridization and pulsed-field gel electrophoresis. From the 200-300 terminal nucleotide sequences of 38 cosmid clones, 56 coding regions were predicted, of which 51 were found to have orthologs in the public databases and five appeared to be unique to H. hepaticus. Of these 51 genes, 36 have orthologs in Helicobacter pylori and 25 display the highest sequence similarity to H. pylori. However, chromosomal positions of these genes are not conserved between these two helicobacters. In addition, 10 H. hepaticus genes had the highest sequence similarity to orthologs in Campylobacter jejuni. The GC content in a randomly selected 21-kb H. hepaticus genomic sequence was 35.8%, which approximates the average between H. pylori (39%) and C. jejuni (30.6%). These results demonstrate that: (1) H. hepaticus is more closely related to H. pylori than C. jejuni; (2) significant genomic alterations exist between H. hepaticus and H. pylori, including gene organization, protein sequences and GC content, probably in part due to specific adaptation to distinct ecological niches.

Animals↗
PubMed2001

Bacterial infection promotes colon tumorigenesis in Apc(Min/+) mice.

The Min mouse, which has a germ line mutation in 1 allele of the Apc tumor suppressor gene, is a model for the early steps in human colorectal cancer. Helicobacter pylori infection, a known risk factor for gastric cancer in humans, causes chronic inflammation and increased epithelial cell proliferation in the stomach. Infection with the bacterium Citrobacter rodentium is known to increase epithelial cell proliferation and to promote chemically initiated tumors in the colon of mice. Min mice infected with C. rodentium at 1 month of age were found to have a 4-fold increase in the number of colonic adenomas at 6 months of age, compared with uninfected Min mice. Most of the colonic adenomas in the infected Min mice were in the distal colon, where C. rodentium-induced hyperplasia occurs. These data demonstrate that bacterial infection promotes colon tumor formation in genetically susceptible mice.

Adenoma↗