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Biomedical subjects

J G Fox

Publications and source records attributed to J G Fox.

At least 145 records · Page 8Linked to original sources
PubMed1996

Helicobacter mustelae-associated hypergastrinemia in ferrets (Mustela putorius furo).

OBJECTIVE: To determine whether ferrets naturally infected with Helicobacter mustelae were hypergastrinemic, compared with ferrets that were specific-pathogen-free (SPF) for H mustelae. DESIGN: Plasma gastrin concentrations in H mustelae-infected and SPF ferrets were measured at 3 time points and compared to determine whether H mustelae was associated with hypergastrinemia. ANIMALS: 21 H mustelae-infected ferrets and 10 SPF ferrets. PROCEDURE: The H mustelae status of the ferrets was confirmed prior to commencement of the study. Gastric endoscopy was used to obtain gastric mucosal pinch biopsy specimens that were processed for rapid-urease assay, microaerophilic culturing, and histologic evaluation. Plasma gastrin concentrations were determined at 3 time points: baseline after a 12-hour nonfeeding period, and 30 and 60 minutes after oral administration of a standardized meal. Gastrin was measured by radioimmunoassay. RESULTS: The results for the H mustelae-infected group (mean +/- SEM pg/ml) were: baseline, 54.4 +/- 2.56; 30 minutes, 94.5 +/- 6.05; and 60 minutes, 82.6 +/- 5.73. The SPF group results were: baseline, 55.8 +/- 7.35; 30 minutes, 80.8 +/- 5.77; and 60 minutes, 59.7 +/- 4.95. There was a significant (P < 0.01) difference at the 60-minute time point between the 2 groups of animals. The H mustelae group had a 17% higher mean gastrin value at 30 minutes. CONCLUSIONS: Helicobacter mustelae is associated with hypergastrinemia in ferrets. CLINICAL RELEVANCE: Helicobacter-induced hypergastrinemia may be related to the pathogenesis of peptic ulcer disease in ferrets.

Animals↗
PubMed1996

Inflammatory large bowel disease in immunodeficient mice naturally infected with Helicobacter hepaticus.

Large bowel disease detected clinically by rectal prolapse was studied in 64 immunodeficient mice (37 athymic NCr-nu/nu, 12 BALB/c AnNCr-nu/nu, 9 C57BL/6NCr-nu/nu, and 6 C.B17/Icr-scid/NCr) naturally infected with Helicobacter hepaticus. Rectal prolapse was found in approximately 5% of immunodeficient mice maintained in a research facility over a period of 3.5 years. All mice had various degrees of chronic proliferative typhlitis, colitis, and proctitis, usually without concomitant hepatitis. Some mice had severe proliferative proctitis with cystic hyperplasia. Histologic study of the large bowel of 48 athymic NCr-nu/nu mice without H. hepaticus infection and housed in another clean facility revealed only 12% of the mice with minimal-to-mild large bowel inflammation. Helicobacter hepaticus infection is associated with large bowel disease in immunodeficient mice but is not seen in H. hepaticus-infected immunocompetent mice. This new pathogenic bacterial infection should be considered as another potential cause or co-factor for rectal prolapse and large bowel disease in mice.

Animals↗
PubMed1996

Evaluation of various oral antimicrobial formulations for eradication of Helicobacter hepaticus.

Helicobacter hepaticus colonizes the cecum and colon of several strains of mice from a variety of commercial suppliers, persistently infects mice, causes chronic hepatitis, is linked to hepatic tumors in A/JCr mice, and has been associated with inflammatory bowel disease of athymic and scid mice. For this reason, eradication of the organism from infected mouse colonies is desirable. We recently reported that amoxicillin or tetracycline-based triple therapy (amoxicillin or tetracycline in combination with metronidazole and bismuth) given by oral gavage 3 times daily for 2 weeks eradicated H. hepaticus in 8- to 10-week-old A/JCr mice. To establish a more convenient therapy regimen for eradicating H. hepaticus, we evaluated water and dietary administration of various antibiotic combinations in A/JCr and DBA/2 mice naturally infected with H. hepaticus. The A/JCr male mice received amoxicillin-based triple therapy in drinking water or by oral gavage, or received tetracycline-based triple therapy in the drinking water. The DBA/2J female mice received amoxicillin-based triple therapy in a specially formulated dietary wafer or by oral gavage, or received enrofloxacin in drinking water. All treatments were given for a 2-week period. Control animals received no treatment. One month after treatment, H. hepaticus was recovered from the liver, cecum, or colon of A/JCr control mice and mice receiving amoxicillin- or tetracycline-based triple therapy in drinking water but not in mice receiving amoxicillin-based triple therapy by oral gavage. Helicobacter hepaticus was not recovered from DBA/2J mice receiving amoxicillin-based triple therapy in dietary wafer or by oral gavage but was recovered from control mice and 7 of 10 mice receiving enrofloxacin in drinking water. Results indicate that amoxicillin-based triple therapy administered in the diet or by oral gavage is effective in eradicating H. hepaticus. Antibiotics administered in the water, however, were not effective in eradicating the organism.

Administration, Oral↗
PubMed1996

A cluster of cases of juvenile mediastinal lymphoma in a ferret colony.

Three cases of juvenile mediastinal lymphoma developed in a laboratory colony of ferrets. Two ferrets became acutely moribund, and one was found dead with no preceding signs of illness. Splenomegaly, hepatomegaly, and a large thoracic mass were the primary features in each case. All three ferrets had multiorgan metastasis of the tumor. Two ferrets were tested for feline leukemia virus and Aleutian disease virus with negative results.

Animals↗
PubMed1996

Proliferative enteropathy of rabbits: the intracellular Campylobacter-like organism is closely related to Lawsonia intracellularis.

The intracellular Campylobacter-like organism associated with proliferative enteropathy of rabbits is closely related to Lawsonia intracellularis, the primary pathogen in porcine intestinal adenomatosis. Polymerase chain reaction primers based on the 16S rRNA gene of L. intracellularis were used to amplify DNA harvested from intestinal tissues of rabbits with severe proliferative intestinal lesions containing curved argentophilic intracellular bacteria. Sequencing of a 180-nucleotide DNA fragment of the 550-base pair-amplified polymerase chain reaction product revealed >98% similarity between the organism associated with the rabbit disease and the homologous sequence found in L.intracellularis.

Animals↗
PubMed1995

Nitric oxide production in relation to spontaneous B-cell lymphoma and myositis in SJL mice.

SJL mice spontaneously develop B cell lymphomas (historically described as reticulum cell sarcomas) by 12 months of age and inflammatory muscle disease (myositis) by 6 months of age. Tumors originate in mesenteric lymph nodes and in Peyer's patches and resemble human germinal center lymphomas. The growth of reticulum cell sarcomas is completely dependent on cytokine production by normal T cells. The spontaneous myositis, which resembles human idiopathic myositis, is characterized by various abnormalities in skeletal muscle, including infiltration with inflammatory cells consisting primarily of macrophages. The participation of different cytokines in the pathogenesis of the lymphoma and the massive invasion of macrophages into muscle tissues led us to investigate the possible involvement of nitric oxide (NO.), which is known to be synthesized by activated macrophages under inflammatory conditions. Elevated NO. production, measured by urinary nitrate excretion, by SJL mice in comparison with BALB/c control mice was observed as early as 7 weeks of age. Both aging and degree of spontaneous myositis correlated with increased nitric oxide production. Oral administration of N-monomethyl-L-arginine, an inhibitor of nitric oxide synthase (NOS), reduced urinary nitrate excretion and also the severity of myositis. Immunohistochemical analysis revealed the presence of inducible NOS (iNOS) in cells in the spleen, lymph nodes, and skeletal muscle. The iNOS is primarily responsible for the enhanced nitric oxide production. Morphology of cells that stained positive for iNOS was similar to that of macrophages infiltrating into the affected tissues. Chronic production of elevated amounts of nitric oxide by the SJL mice, therefore, provides a useful in vivo model for future studies of cellular damage resulting from endogenously produced NO.in combination with oxygen radicals.

Amino Acid Oxidoreductases↗
PubMed1995

Rabbit and ferret parietal cell inhibition by Helicobacter species.

We tested sonicates of Helicobacter pylori, H. mustelae, and H. felis for inhibition of acid secretion in rabbit and ferret isolated gastric glands. Three H. pylori strains, two of three H. mustelae strains, and two H. felis strains significantly inhibited acid secretion in rabbit cells by 95.2-93.3%, 55.9% and 96.4%, and 83.4-96%, respectively. All Helicobacter strains examined inhibited acid secretion by ferret cells by 65.3-76.8%, 89.1-97.6%, and 85.8-92.8%. H. pylori inhibited acid secretion after stimulation with histamine and isobutylmethylxanthine or with 8-bromo-cyclic adenosine monophosphate (P < 0.05 for all tests). These findings demonstrate that acid inhibition is a property common to the three Helicobacter species tested. It occurs independently of the mammalian origin of the parietal cell, and it does not involve blockade of histamine-2 receptors.

1-Methyl-3-isobutylxanthine↗
PubMed1995

Vitamin E enhances the lymphatic transport of beta-carotene and its conversion to vitamin A in the ferret.

BACKGROUND/AIMS: beta-Carotene and alpha-tocopherol may have either antagonistic or synergistic effects on each other's absorption and metabolism. The effects of both physiological and pharmacological concentrations of alpha-tocopherol on the absorption and metabolism of beta-carotene in ferret intestine were determined. METHODS: A high concentration of beta-carotene was perfused through the upper portion of the small intestine of ferrets in vivo with varying levels of alpha-tocopherol. The effluent of a mesenteric lymph duct cannulation, the intestinal mucosal scraping, and portal vein blood were sampled and analyzed by high-performance liquid chromatography. RESULTS: The lymphatic transport of beta-carotene was enhanced 4-fold by alpha-tocopherol at a physiological dose and 12-21-fold at a pharmacological dose. The lymphatic transport of alpha-tocopherol was linearly (r = 0.8; P < 0.05) related to the luminal alpha-tocopherol concentration even in the presence of a high concentration of beta-carotene. Furthermore, alpha-tocopherol increased the conversion of beta-carotene into retinol in the intestine in a dose-dependent manner. CONCLUSIONS: alpha-Tocopherol has a positive effect on the intestinal absorption of intact beta-carotene and may modulate the metabolic conversion of beta-carotene into retinoids.

Absorption↗
PubMed1995

Effect of Helicobacter mustelae infection on ferret gastric epithelial cell proliferation.

The effect of Helicobacter mustelae infection on gastric epithelial proliferation was studied in ferrets colonized with H.mustelae and specific pathogen-free (SPF) ferrets not infected with H.mustelae. Thirteen H. mustelae-infected ferrets between the ages of 13 and 32 months and 16 SPF ferrets between 6 and 18 months were analyzed. Bacterial cultures, urease tests and Warthin-Starry stains were used to identify H.mustelae. Tissues obtained from the antrum and the body regions of the stomach were assayed by proliferating cell nuclear antigen (PCNA) immunohistochemistry and measured using a computerized color image analysis system. PCNA-expressing gastric epithelia in the antrum and the body regions were significantly increased in the H.mustelae-infected ferrets versus the SPF ferrets (P < 0.001). PCNA positivity in the antrum regions of both the H.mustelae-infected ferrets and SPF ferrets was significantly higher than that of the body regions (P < 0.001). Comparison of the histopathology of infected ferrets indicated that PCNA positivity correlated with the histological severity of gastritis. This study suggests that cell proliferation in ferret gastric mucosa increases with H.mustelae infection and provides evidence that PCNA is a useful biomarker for studying the changes in cell kinetics in the ferret stomach. The data also further support the use of the H.mustelae-infected ferret as an animal model for studying the pathogenesis of Helicobacter pylori-induced gastric diseases of humans.

Animals↗
PubMed1995

Long-term supplementation of canthaxanthin does not inhibit gastric epithelial cell proliferation in Helicobacter mustelae-infected ferrets.

The effect of canthaxanthin (CX), a nonprovitamin A carotenoid, on gastric epithelial proliferation was studied in ferrets colonized with Helicobacter mustelae, which causes a chronic gastritis and an increased gastric epithelial cell proliferation. Seven spayed female ferrets were dosed by gavage with CX beadlets (50 mg/kg body wt, 5 d/wk) over 2 y, whereas seven control animals were given placebo beadlets. At the end of the 2-y-period, ferrets were killed, and gastric tissues were obtained from the antrum and body regions. A cell-proliferating biomarker, proliferating cell nuclear antigen (PCNA), was assayed by immunohistochemistry. The PCNA positivity was measured by a computer-based image analysis system. Serum concentrations of carotenoids, retinoids and tocopherols were analyzed by HPLC. Serum antioxidant status was measured by the oxygen radical absorbance capacity (ORAC) assay. The PCNA positivity in both antrum and body regions was not significantly different between CX-fed ferrets and controls. Serum CX concentrations were significantly higher in CX-fed ferrets vs. controls (P < 0.001), whereas levels of other carotenoids, retinoids and tocopherols were not significantly different. The ORAC values were not significant different between groups. This study does not suggest inhibitory effects of CX on gastric epithelial cell proliferation in H. mustelae infected ferrets.

Animals↗
PubMed1995

Supplementing ferrets with canthaxanthin affects the tissue distributions of canthaxanthin, other carotenoids, vitamin A and vitamin E.

To study the effects of canthaxanthin supplementation on the tissue distribution of canthaxanthin, other carotenoids, vitamin A and vitamin E, 26 spayed female ferrets (2 mo of age) were used. Ferrets were assigned to receive a commercial ferret diet and a gavage of canthaxanthin [50 mg/(kg body wt.d)] or a gavage of placebo beadlets (0 mg canthaxanthin) 5 d/wk. Serum canthaxanthin concentrations in the canthaxanthin-fed group increased from 0 at baseline to 37.76 +/- 5.34 nmol/L trans and 77.10 +/- 12.60 nmol/L cis canthaxanthin at 12 mo. Further accumulation of canthaxanthin did not occur with continuous dosing. After 2 y of receiving canthaxanthin beadlets by gavage, the ferrets did not show a detectable concentration of canthaxanthin in the eyes, nor did they have clinical signs of toxicity. Canthaxanthin concentrations were highest in liver, with high concentrations also seen in fat, lung and small intestine. The sum of alpha and beta-carotene concentrations detected in livers was significantly higher in the canthaxanthin-fed group than in the placebo-fed group, but not significantly higher when individual carotenes were compared. However, alpha-tocopherol concentrations in the livers and lungs and lutein/zeaxanthin in the fats of the ferrets fed canthaxanthin were significantly lower than in those fed the placebo. Retinoid concentrations in tissues of the ferrets fed canthaxanthin were not different from those of the placebo-fed group. The effects of canthaxanthin supplementation on other antioxidants and vitamin A nutrients demonstrate either a synergistic or antagonistic relationship, depending on the specific tissue assayed.

Adipose Tissue↗
PubMed1995

In-vitro hepatotoxic factor in Helicobacter hepaticus, H. pylori and other Helicobacter species.

Several inbred strains of mice in closed breeding colonies were found to have spiral-shaped bacteria associated with active, chronic hepatitis. A new species of Helicobacter, H. hepaticus, was isolated from the infected livers of some strains of mice. Other strains of mice were colonised with H. hepaticus in the caecum and colon, but not the liver. Filtersterilised supernatant fluid from five strains of H. hepaticus was tested in a mouse liver cell line (ATCC no. CCL 9.1) for cytotoxic activity. All strains produced a toxic factor causing morphological changes in the cells at dilutions up to 1 in 1000. Toxicity was observed after exposure to the supernatant fluid for 48-72 h. Other Helicobacter spp. that also produced the cytopathic effect (CPE) in the liver cell line were H. felis, H. acinonyx, H. pylori and one strain of H. mustelae. "Helicobacter rappini" and H. muridarum did not cause CPE in the liver cells. The soluble factor was stable at 4 degrees C for up to 3 months. It was also stable at 56 degrees C for 30 min, but was inactivated by boiling for 15 min. It was inactivated by incubation with trypsin. A partially purified preparation of the cytotoxin had a mol. wt of c. 100,000 and did not have urease activity. The cytotoxin produced by H. hepaticus did not cause vacuole formation in HeLa cells.

Animals↗
PubMed1995

Glomerular charge selectivity in type 1 (insulin-dependent) diabetes mellitus.

Glomerular charge selectivity was assessed using the ratio of the clearance of pancreatic isoamylase to the clearance of the more anionic salivary isoamylase (CPAm/CSAm) in 12 normal subjects and 50 patients with Type 1 diabetes: 13 with normal albumin excretion and short duration of diabetes (< 5 years), 15 with normal albumin excretion and long duration of diabetes (> 15 years), 13 with microalbuminuria, and 9 with clinical nephropathy. None had serum creatinine > 200 mumol l-1. There were no significant differences in CPAm/CSAm between the normal subjects and the two groups of normoalbuminuric patients with Type 1 diabetes. CPAm/CSAm was significantly lower in diabetic patients with microalbuminuria or clinical nephropathy than in normoalbuminuric patients with Type 1 diabetes. When the 37 patients with normoalbuminuria and long-standing diabetes, microalbuminuria, and nephropathy were considered together, there was a significant negative correlation between CPAm/CSAm and albumin excretion rate (rs = 0.71, p < 0.001). Progressive impairment of glomerular charge selectivity at the molecular size of amylase (molecular mass 56 kDa) accompanies increasing albuminuria in Type 1 diabetes.

Adult↗
PubMed1995

Evaluation of antibiotic therapies for eradication of Helicobacter hepaticus.

The newly recognized murine pathogen Helicobacter hepaticus is known to colonize the ceca and colons of several strains of mice from a variety of commercial suppliers. Additionally, the organism persistently infects mice, causes a chronic hepatitis, and is linked to hepatic tumors in the A/JCr inbred mouse strain. For this reason, eradication of the organism from infected mouse colonies is desirable. Treatment modalities for eradication of H. hepaticus from the gastrointestinal system consisted of oral administration of various antibiotic combinations previously evaluated for eradication of experimental H. felis gastric infection in mice. A/JCr mice (8 to 10 weeks old) naturally infected with H. hepaticus were divided into six treatment groups of 10 animals each. Animals received monotherapy of amoxicillin, metronidazole, or tetracycline or triple therapy of amoxicillin-metronidazole-bismuth (AMB) or tetracycline-metronidazole-bismuth (TMB). All medications were administered by oral gavage three times daily for 2 weeks. One month after the final treatment, mice were euthanatized and livers, ceca, and colons were cultured for H. hepaticus. All untreated control animals had H. hepaticus isolated from the cecum and/or colon. H. hepaticus was not recovered from the livers, ceca, or colons of the AMB or TMB treatment groups. All animals receiving the various antibiotic monotherapies had H. hepaticus isolated from the cecum and colon. We conclude that at the doses and the route evaluated, AMB and TMB triple therapies are effective for eradication of H. hepaticus in 8- to 10-week old A/JCr mice.

Amoxicillin↗
PubMed1995

Effect of oral immunization with recombinant urease on murine Helicobacter felis gastritis.

The ability of oral immunization to interfere with the establishment of infection with Helicobacter felis was examined. Groups of Swiss Webster mice were immunized orally with 250 micrograms of Helicobacter pylori recombinant urease (rUrease) and 10 micrograms of cholera toxin (CT) adjuvant, 1 mg of H. felis sonicate antigens and CT, or phosphate-buffered saline (PBS) and CT. Oral immunization with rUrease resulted in markedly elevated serum immunoglobulin G (IgG), serum IgA, and intestinal IgA antibody responses. Challenge with live H. felis further stimulated the urease-specific intestinal IgA and serum IgG and IgA antibody levels in mice previously immunized with rUrease but activated primarily the serum IgG compartment of PBS-treated and H. felis-immunized mice. Intestinal IgA and serum IgG and IgA anti-urease antibody responses were highest in rUrease-immunized mice at the termination of the experiment. Mice immunized with rUrease were significantly protected (P < or = 0.0476) against infection when challenged with H. felis 2 or 6 weeks post-oral immunization in comparison with PBS-treated mice. Whereas H. felis-infected mice displayed multifocal gastric mucosal lymphoid follicles consisting of CD45R+ B cells surrounded by clusters of Thy1.2+ T cells, gastric tissue from rUrease-immunized mice contained few CD45R+ B cells and infrequent mucosal follicles. These observations show that oral immunization with rUrease confers protection against H. felis infection and suggest that gastric tissue may function as an effector organ of the mucosal immune system which reflects the extent of local antigenic stimulation.

Administration, Oral↗
PubMed1995

Helicobacter pylori-induced gastritis in the domestic cat.

Helicobacter pylori has been cultured from the inflamed gastric mucosae of naturally infected cats; the lesions in H. pylori-infected cat stomachs mimic many of the features seen in H. pylori-infected human stomachs. To determine whether H. pylori-negative specific-pathogen-free cats with normal gastric mucosae were susceptible to colonization by this bacterium and whether gastritis developed after infections, four H. pylori-negative cats treated with cimetidine were orally dosed three times with 3 ml (1.5 x 10(8) CFU/ml) of H. pylori every 4 days. All four cats became persistently colonized as determined by gastric cultures and PCRs from serial gastric biopsy samples and necropsy samples at 7 months postinfection. H. pylori was not isolated from the two control cats, nor were their gastric tissues positive by PCR; one of the two cats had a few focal lymphocytic aggregates in the body submucosa, whereas the second cat had a normal gastric mucosa. All four H. pylori-infected cats had multifocal gastritis consisting of lymphoid aggregates plus multiple large lymphoid nodules, which were most noticeable in the antral mucosa. In addition, one H. pylori-infected cat had a moderate diffuse infiltration of polymorphonuclear leukocytes in the subglandular region of the antrum. H. pylori-like organisms were focally distributed in glandular crypts of the antrum. Two of the H. pylori-infected cats had significant (eightfold) increases over baseline in levels of immunoglobulin G H. pylori serum antibody. The H. pylori isolates from the four experimentally infected cats had restriction fragment length polymorphism patterns specific for the flaA gene that were identical to those of the inoculating strain. H. pylori readily colonizes the cat stomach and produces persistent gastritis.

Animals↗