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Biomedical subjects

J G Fox

Publications and source records attributed to J G Fox.

At least 271 records · Page 15Linked to original sources

Effects of ascorbic acid and thiocyanate on nitrosation of proline in the dog stomach.

To elucidate the factors governing the formation of N-nitrosamines in the stomach, the formation of N-nitrosoproline (NPro) was studied under controlled conditions, using a dog equipped with a Thomas cannula. Solutions containing nitrite, proline and in some cases ascorbic acid and/or SCN-, were infused into the stomach and samples taken to determine gastric [nitrite], [NPro], [ASC], [SCN-] and pH as functions of time. (Brackets indicate molar concentrations; ascorbic acid and ascorbate ion are denoted together by ASC.) Previous work showed that the rapid decline of [nitrite] in the stomach was due primarily to absorption. Additional experiments here in which ASC, proline or NPro were infused together with a non-absorbable marker, in the absence of nitrite, demonstrated that there was negligible absorption or secretion of these substances in the stomach. Thus, changes in [ASC] and [NPro] with time could be interpreted quantitatively in terms of rates of chemical reaction and dilution of the stomach contents. A mathematical model, based on mass balance equations for the various chemical species and chemical kinetic data obtained previously from in vitro studies, was developed for this purpose. The ability of ASC to inhibit nitrosation (by reaction with nitrite) was shown to be highly dependent on initial [ASC] and on the rate of entry of O2 into the stomach from blood. The rate of NPro formation in the absence of ASC and SCN-, the inhibitory effects on nitrosation of ASC and the catalytic effects of SCN-, were all accurately predicted by the mathematical model. This suggests that similar models may prove useful in estimating rates of intragastric N-nitrosation reactions in humans, under various assumed conditions.

Animals↗

Gastric colonization by Campylobacter pylori subsp. mustelae in ferrets.

Campylobacter pylori subsp. mustelae was cultured from both normal and inflamed gastric mucosa of ferrets. Examination of neonatal, juvenile, and adult ferrets established that the gastric mucosa in the majority of preweanling (age, less than 6 weeks) ferrets sampled were not colonized with C. pylori subsp. mustelae, whereas the gastric mucosa of 100% of adult ferrets were colonized with this gastric organism. C. pylori subsp. mustelae was isolated from the gastric mucosa on a sequential basis from nine ferrets during a several-month period, inferring either persistent colonization or frequent reinfection with C. pylori subsp. mustelae.

Age Factors↗

Serum cortisol radioimmunoassay values in the normal ferret and response to ACTH stimulation and dexamethasone suppression tests.

Cortisol values were obtained from 39 ferrets, Mustela putorius furo, by using a commercial radioimmunoassay. Sera from 25 males (18 intact, 7 neutered) and 14 females (7 intact, 7 spayed) were assayed. Resting serum cortisol values ranged from 0.13 to 2.70 micrograms/dl for males (mean = 0.93 +/- 0.63 micrograms/dl), and 0.55 to 1.84 micrograms/dl for females (mean = 0.86 +/- 0.29 microgram/dl). The resting cortisol values of both males and females were comparable to those of the cat (1.0 to 3.0 micrograms/dl). A 7 year old male ferret with suspected hyperadrenocorticism and an adrenal mass had a cortisol level of 8.1 micrograms/dl. Adrenal cortical carcinoma was the histologic diagnosis. One adult female ferret had a cortisol level of 3.30 micrograms/dl. This animal also had proliferative colitis upon necropsy. An ACTH stimulation test (1 U/kg IM) and a low-dose dexamethasone suppression test (0.1 mg/kg) were performed on 10 ferrets. Post-ACTH serum cortisol levels increased by an average of 89%. Post-dexamethasone serum cortisol values decreased by an average of 18% 6 hours post-injection.

Adrenocorticotropic Hormone↗

Serum thyroxine and triiodothyronine radioimmunoassay values in the normal ferret.

The European ferret, Mustela putorius furo, has become increasingly popular as an animal model in biomedical research. However, certain important normal clinical data have not been established for the ferret. In this study, serum thyroxine (T4) and 3,3',5-triiodothyronine (T3) values were obtained from ferrets by the use of commercial radioimmunoassays. Sera from 44 animals, 31 males (27 intact and 4 castrated) and 13 females (10 intact and 3 spayed) were assayed. Serum T4 values ranged from 1.01-8.29 micrograms/dl for males (mean = 3.24 +/- 1.65 micrograms/dl), and 0.71-3.43 micrograms/dl for females (mean = 1.87 +/- 0.79 micrograms/dl). Serum T4 values of adult female ferrets, juvenile ferrets (less than 1 year old) of either sex, and castrated males were similar to the normal T4 values of the cat, 1.20-3.80 micrograms/dl. Intact adult male ferrets had higher serum T4 values which were more comparable to those of the normal dog 1.52-3.60 micrograms/dl. Serum T3 values ranged from 0.45-0.78 ng/ml for males (mean = 0.58 +/- 0.09 ng/ml), and 0.29-0.73 ng/ml for females (mean = 0.53 +/- 0.13 ng/ml). These values are comparable to those of dogs and cats which are 0.50-1.50 ng/ml.

Animals↗

Campylobacter-like omega intracellular antigen in proliferative colitis of ferrets.

Proliferative colitis in the ferret consistently displays, along with marked proliferation of mucosal cells, intracytoplasmic campylobacter-like organisms within the apical portion of the epithelial cells. Fluorescent antibody to "omega" campylobacter antigen present in porcine intestinal adenomatosis and hamster proliferative ileitis was demonstrated at the site of bacterial colonization within hyperplastic epithelial cells of six colons from ferrets affected with proliferative colitis.

Animals↗

Campylobacter jejuni/coli in commercially reared beagles: prevalence and serotypes.

A 5 year longitudinal study involving 187 commercially reared beagles from three suppliers was undertaken to determine prevalence and serotypes of Campylobacter jejuni and C. coli. Campylobacter jejuni or C. coli was isolated from the feces in 62 of 177 asymptomatic beagles and 8 of 10 dogs with diarrhea for an overall prevalence of 37%. A total of 36 isolates were serotyped on the basis of thermostable antigens with 20 antisera prepared against frequently occurring serotypes isolated from humans with campylobacter associated enteritis (15 C. jejuni, 5 C. coli serotypes). Of these isolates, 17 (47%) serotyped with antisera to 7 C. jejuni serotypes frequently isolated in human cases of enteric campylobacteriosis (serotypes 1, 4, 10, 16, 18, 19, 37). One C. coli reacted to antisera 24, 34, 37, one strain of C. coli to antisera type 37, and another C. coli to antisera type 34. All three C. coli belonged to serotypes frequently encountered in diarrheic human patients.

Animals↗

Experience of the Manitoba Perinatal Screening Program, 1965-85.

The Manitoba Perinatal Screening Program is guided by a committee of medical specialists with skills in the diagnosis and management of disorders of metabolism in the newborn. The program is voluntary and is centralized at Cadham Provincial Laboratory, in Winnipeg. A filter card blood specimen is collected from newborns on discharge from hospital, and a filter card urine sample is collected and mailed to the laboratory by the mother when the infant is about 2 weeks of age. The overall compliance rates for the blood and urine specimens are approximately 100% and 84% respectively. The blood specimen is screened for phenylalanine and other amino acids, thyroxine, galactose, galactose-1-phosphate and biotinidase. The urine specimen is screened for amino acids, including cystine, as well as methylmalonic acid and homocystine. Between 1965 and 1985, 83 cases of metabolic disorders were detected, including 23 cases of primary hypothyroidism, 14 of classic phenylketonuria, 5 of galactosemia variants, 3 of galactosemia, 2 of maple syrup urine disease and 1 of hereditary tyrosinemia. The direct cost per infant screened is $5.50, and the cost:benefit ratio is approximately 7.5:1. Maternal serum alpha-fetoprotein screening is being made available as the necessary supporting clinical facilities become available. On the basis of this experience, the author outlines the components that are important for an effective screening program.

Costs and Cost Analysis↗

Hyperadrenocorticism in a ferret.

A 7-year-old adult male ferret had progressive hair loss that was bilaterally symmetric. Also clinically evident were severe dehydration, polydipsia, muffled heart sounds, weak femoral pulses, hepatomegaly, lethargy, weakness, temporal muscular atrophy, dyspnea, and weakness. The blood profile of the ferret indicated profound leukopenia, eosinopenia, and high phosphorus, BUN, creatinine, and potassium concentrations, as well as high aspartate transaminase activity; the albumin concentration was low. The serum cortisol concentration was 8.1 micrograms/dl. Necropsy and histologic findings confirmed a diagnosis of hyperadrenocorticism, complicated by dilatative cardiomyopathy, chronic active hepatitis, and renal disease.

Adrenal Cortex Neoplasms↗

The single dose pharmacokinetics of bisoprolol (10 mg) in renal insufficiency: the clinical significance of balanced clearance.

The pharmacokinetics of the beta-blocking agents presently available render some subject to accumulation in renal or hepatic failure. Bisoprolol is one of the beta blockers possessing balanced clearance (both renal and hepatic clearance) which prevents such accumulation even in the case of complete failure of kidneys or liver. The single dose pharmacokinetics of bisoprolol were studied in patients with varying degrees of renal impairment and in healthy controls. Correlations were demonstrated between creatinine clearance and elimination half-life, mean residence time, area under the curve, total clearance and maximum concentration in those with renal dysfunction. The elimination half-life increased by a factor of 1.96 in those with severe renal dysfunction. Because of its balanced clearance, it is unlikely that accumulation of bisoprolol would occur beyond a factor of 2 on dosing to a steady state. The 48 hour plasma levels in the patients on dialysis were similar to those of the patients with severe renal dysfunction. This suggest that accumulation is unlikely, even in end stage renal failure. Bisoprolol may be used safely in patients with renal dysfunction. No adjustment of dose is necessary for those with mild to moderate dysfunction, but in severe or end stage renal failure the dose should not exceed 10 mg once daily.

Administration, Oral↗

Rederivation of MHV and MEV antibody positive mice by cross-fostering and use of the microisolator caging system.

This study established the feasibility of rederiving numerous mouse hepatitis virus (MHV) and mouse encephalomyelitis virus (MEV) antibody positive strains of mice using cross fostering techniques and a new caging system, thus permitting introduction of virus antibody free mice into a barrier facility. Serologic status of dams within the nucleus breeding colony was determined, and all mice within the breeding colony were housed in individual Microisolator cages. Specific pathogen free (SPF) foster mothers purchased from a commercial source were determined to have no detectable serum antibody to 11 murine viruses including MEV and MHV. Pups delivered naturally from time pregnant dams were cross fostered onto the SPF foster dams. The procedure of cross fostering was conducted within a positive flow, HEPA-filtered, mass air displacement unit within 24 hours of parturition. The virus status of pups from 49 litters was monitored serologically at weaning and again at 6 weeks of age. All cross fostered litters were serologically negative for antibody to mouse hepatitis virus. Seven of 29 litters were negative for MEV antibody titer using this cross fostering technique. Those litters negative serologically to both MHV and MEV (at 3 and 6 weeks) were transferred to a barrier facility and held in isolation. All rederived mice transferred to the barrier facility remained negative for MHV and MEV when sampled at 12 weeks of age.

Animals↗

Hematuria in rabbits.

A nine year retrospective study of hematuria in 14 New Zealand White rabbits was conducted to classify possible etiologies of this clinical finding. Physical examination, laboratory tests, radiography and postmortem examination were utilized in most cases to verify the presence of hematuria and to determine its etiology. Uterine adenocarcinoma was diagnosed in two rabbits. Three rabbits had uterine polyps with hemorrhage. Renal infarction with hemorrhage was diagnosed in three rabbits. Urolithiasis with secondary urethral obstruction and hemorrhagic cystitis was identified as the cause of hematuria in four rabbits. Other causes of hematuria included chronic cystitis, disseminated intravascular coagulation, bladder polyps and pyelonephritis. Hematuria of undetermined origin was observed in one rabbit. This last [corrected] case was negative for both blood and porphyrin in the urine, but positive for excess levels of urobilin, the oxidative product of urobilinogen. This case illustrates that hyperpigmented urine should be a rule out in all cases of suspected hematuria in rabbits.

Adenocarcinoma↗

Development of large numbers of mast cells at sites of idiopathic chronic dermatitis in genetically mast cell-deficient WBB6F1-W/Wv mice.

The normal skin and other tissues of adult mast cell-deficient WBB6F1-W/Wv or WCB6F1-Sl/Sld mice contain less than 1.0% the number of mast cells present in the corresponding tissues of the congenic normal (+/+) mice. As a result, genetically mast cell-deficient WBB6F1-W/Wv or WCB6F1-Sl/Sld mice are widely used for studies of mast cell differentiation and function. We found that mast cells developed at sites of idiopathic chronic dermatitis in WBB6F1-W/Wv mice and that the number of mast cells present in the skin of WBB6F1-W/Wv mice was proportional to the severity of the dermatitis (in ear skin, there were 33 +/- 4 mast cells/mm2 of dermis at sites of severe dermatitis v 9 +/- 3 at sites of mild dermatitis, 0.8 +/- 0.3 in skin without dermatitis, and 100 +/- 7 in the normal skin of congenic WBB6F1-+/+ mice; in back skin, the corresponding values were 2.0 +/- 0.6, 1.1 +/- 0.9, 0.025 +/- 0.025, and 26.2 +/- 3.2). The development of mast cells was a local, not systemic, consequence of the dermatitis. Thus, WBB6F1-W/Wv mice with severe dermatitis lacked mast cells in skin not showing signs of dermatitis and also in the peritoneal cavity, stomach, cecum, and tongue. Idiopathic chronic dermatitis was not associated with the local development of mast cells in WCB6F1-Sl/Sld mice, a mutant whose mast cell deficiency is due to a mechanism distinct from that of WBB6F1-W/Wv mice. These findings may have implications for understanding the nature of the mast cell deficiency in WBB6F1-W/Wv and WCB6F1-Sl/Sld mice and for the use of these mutants to analyze mast cell differentiation and function.

Animals↗

Comparison of methods to diagnose an epizootic of Corynebacterium kutscheri pneumonia in rats.

An outbreak of Corynebacterium kutscheri pneumonia occurred in a colony of laboratory rats. Diagnostic methods compared on a prospective basis included (1) an enzyme-linked immunosorbent assay (ELISA) for serum antibody to C. kutscheri; (2) C. kutscheri isolation from retrograde nasal wash, cervical lymph nodes, tracheal wash, lung homogenate; and (3) histopathology. C. kutscheri was isolated from one or more of the cultured sites from suspected cases, but no individual rat yielded C. kutscheri from all of the sites. The presence of histological lung lesions was the most frequent indicator of infection (8 of 9 suspected cases), followed by isolation of C. kutscheri from lung homogenate (5 of 6), ELISA for serum antibody (6 of 8), and isolation of C. kutscheri from cervical lymph node (4 of 8). Isolation of C. kutscheri from nasal wash (1 of 9) was the least sensitive indicator of infection. ELISA antibody was not detected in rats which had normal lungs and did not harbor C. kutscheri. It was concluded that ELISA provides noninvasive means for detecting infection and cervical lymph node culture increase the potential for successful isolation of the agent in C. kutscheri infected rats.

Animals↗

The ferret as a model for endogenous synthesis and metabolism of N-nitrosamines.

We have begun to evaluate the ferret as a model for studying gastric nitrosation and nitrosamine metabolism. Jugular cannulation allows convenient dosing and sampling of blood, and this technique has been used to study clearance of N-nitrosodimethylamine (NDMA) after intravenous, intraperitoneal and intragastric administration. NDMA metabolism can be inhibited by 4-methylpyrazole for up to 24 h; the accumulation of endogenously-synthesized NDMA can therefore be observed in animals following pretreatment with this compound. We have studied endogenous NDMA synthesis in animals dosed with dimethylamine and nitrite and in animals to which no NDMA precursors were administered.

Animals↗