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Biomedical subjects

R R Fox

Publications and source records attributed to R R Fox.

At least 37 records · Page 2Linked to original sources
PubMed1982

Ocular complications.

Ocular complications of diabetes in humans are reviewed briefly, and experimental models available for study of the complications are described. Potentially suitable models include not only diabetic animals, but also nondiabetic animals in which analogous lesions have been demonstrated. Many abnormalities of the lens, cornea, iris, and retina comparable to those of diabetes in humans may be observed in diabetic animals, although all abnormalities are not necessarily observed in every species. Retinal changes, in particular, may occur in diabetic animals of several species, but only in large animals (dogs, primates) have saccular capillary aneurysms been reproduced consistently, together with other retinal changes typical of diabetes in humans. A few examples of the uses of animal models are offered, and attention is called to a lack of animal models of proliferative diabetic retinopathy and of rubeosis iridis.

Animals↗
PubMed1982

Identification of genetically homozygous rapid and slow acetylators of drugs and environmental carcinogens among established inbred rabbit strains.

Liver and gut mucosa N-acetyltransferase (NAT) cytosol (105,000 x g) was prepared from selected lines of New Zealand White rapid and slow acetylator rabbits bred and housed at the University of Michigan, and from inbred and partially inbred rabbits obtained from The Jackson Laboratory. Liver NAT activity was determined with p-aminobenzoic acid, p-aminosalicyclic acid, procainamide, sulfamethazine, isoniazid and 2-aminofluorene as substrates. Gut mucosal NAT activity was determined with 2-aminofluorene. A gene dose-response relationship was observed for both liver NAT and gut mucosa NAT with all substrates tested. Highest levels were always observed in homozygous rapid acetylator inbred strains (B/J, III/J, IIIC/J, III/DwJ, IIIEP/J and IIIVO/J), lower levels in obligate heterozygous rapid acetylator rabbits and lowest levels in homozygous slow acetylator inbred (ACEP/J, III/cdJ, IIIVO/ahJ, and IIIVO/vptJ) and outbred rabbits. The differences in magnitude of liver NAT activity level between acetylator genotypes was dependent on the substrate employed, progressively increasing in the following order: p-aminobenzoic acid, p-aminosalicyclic acid, procainamide, sulfamethazine, isoniazid, 2-aminofluorene. The determination of kinetic constants for liver p-aminosalicyclic acid NAT activity indicated a 2-fold difference in apparent Vmax between rapid acetylator genotypes and a 30-fold difference between rapid and slow acetylator phenotypes. In addition, the apparent Km for p-aminosalicyclic acid was significantly lower in the slow acetylators than in the rapid acetylators.

Acetylation↗
PubMed1982

Association of arylhydroxamic acid N,O-acyltransferase and genetically polymorphic N-acetyltransferase in established inbred rabbit strains.

Partially purified liver preparations from 17 inbred and partially inbred rabbit strains were assayed for polymorphic N-acetyltransferase (NAT) and arylhydroxamic acid N,O-acyltransferase (AHAT) activities. The AC/J, AX/J, B/J, WH/J, X/J, Y-l/J, III/J, IIIC/J, III/DwJ, IIIEP/J and IIIVO/J inbred strains were identified as rapid acetylators and had high AHAT activity. The ACEP/J, AXBU/J, OS/J, III/cdJ, IIIVO/ahJ and IIIVO/vptJ strains were identified as slow acetylators and had low AHAT activity. These findings provide added evidence for the hypothesis that polymorphic NAT and AHAT activities are properties of the same enzyme. Additional studies in five of the rapid acetylator strains showed that they had significantly higher levels of liver NAT activity towards other arylamine acetylator predictor drugs and carcinogens than did obligate heterozygous (Rr) rapid acetylators from our rabbit colony. This indicates that the inbred animals are homozygous (RR) rapid acetylators and that there is a gene-dose response difference between the two rapid acetylator genotypes. Availability of established inbred and partially inbred strains shown to possess both acetylator phenotypes enhances the opportunity for using the rabbit as a genetic model for evaluating the role of the isoniazid acetylator polymorphism as a host factor in arylamine-related carcinogenesis.

Acetyltransferases↗
PubMed1981

Genetic and physiological aspects of cholesterol accumulation in hyperresponding and hyporesponding rabbits.

After a 5 week period of feeding a cholesterol-rich diet to rabbits, hyperresponders with high plasma cholesterol levels and hyporesponders with low plasma cholesterol levels could be distinguished from normal responders. The response was found to be correlated with the esterase genotype at the Est-2 locus. The increase in total body cholesterol was higher in hyper-than in hyporesponders. In both groups most of the accumulated dietary cholesterol was found in plasma and liver. Adrenal weight and plasma corticosterone levels were more increased in hyper- than in hyporesponders. The cholesterol-rich diet resulted in an augmentation of liver lipase and lipoprotein lipase activities. These lipolytic activities were more increased in hyper- than in the hyporesponders.

Adrenal Glands↗
PubMed1981

In vitro culture of rabbit growth plate chondrocytes. 2. Chondrodystrophic mutants.

The epiphyseal plates of newborn normal (Cd/?), dwarf (Dw/Dw) and achondroplastic (ac/ac) rabbits were grown in organ culture for 48 hours. The 3H-thymidine labeling index of proliferating zone chondrocytes from both mutants was below that of normals. The generation time of Dw/Dw animals was longer than that of normals (greater than 24 vs. 17 hours respectively). Inasmuch as the medium was supplemented with 10% fetal calf serum, which presumably contains somatomedin, these data suggest that the Dw/Dw mutant cannot be considered simply a model for pituitary dwarfism. Pituitary fibroblast growth factor (FGF), 50ng/ml, decreased the labeling index of chondrocytes from both Dw/Dw and ac/ac animals. Thus neither a lack of FGF nor an end-organ non-responsiveness to this factor seems to play a role in the pathogenesis of either growth disturbance.

Achondroplasia↗
PubMed1981

Venereal spirochetosis of rabbits: description and diagnosis.

Venereal spirochetosis of rabbits was studied in naturally infected rabbits from an enzootically infected colony containing inbred, partially inbred, and mutant bearing rabbits, and in experimentally infected rabbits from a hysterectomy-derived colony. Naturally and experimentally induced genital lesions were similar clinically and histologically. The most common site of lesions in naturally infected rabbits was the vulva or prepuce. Other sites, in descending order of frequency, were anal region, nose, eyelid, and lip. Clinical appearance of lesions varied from erythematous macules or papules to erosions, ulcers, and crusts. Histological examination of lesions confirmed the presence of erosions, ulcers, and crusts and, in addition, revealed acanthosis and infiltration of the dermis by plasma cells and macrophages. Dark field examination of scrapings from lesions was superior to several other methods for detection of Treponema cuniculi in lesions. The rapid plasma reagin test detected more infected rabbits than examination of lesions. The frequency of false positive rapid plasma reagin tests was low. The frequency of false negative reagin tests varied with the stage of disease.

Animals↗
PubMed1981

Venereal spirochetosis of rabbits: epizootiology.

Venereal spirochetosis of rabbits was studied in an enzootically infected conventional rabbit colony. Differences in the susceptibility to and expression of venereal spirochetosis among different inbred or partially inbred strains of rabbits were observed. Significant differences between frequency of lesions in adult male or female rabbits were not observed. Significant differences between the frequency of lesions in breeders or non-breeders were not observed in the 6-12 month age group. However, significant differences between the frequency of lesions in breeders and non-breeders were observed when different ages were pooled. The frequency of venereal spirochetosis in rabbits less than 6 months of age was lower than that in adult rabbits. Newborn fostering experiments indicated that infection occurred at birth and during the suckling period. Evaluation of hysterectomy-derived offspring of infected dams suggested venereal spirochetosis was eliminated by hysterectomy-derivation. Venereal spirochetosis was successfully transmitted by topical or intradermal-subcutaneous genital inoculation of adult rabbits. Adult rabbits were more susceptible to experimental venereal spirochetosis than neonates. The above conclusions were based on clinical and serological observations.

Animals↗
PubMed1981

Venereal spirochetosis of rabbits: eradication.

Venereal spirochetosis of rabbits, caused by Treponema cuniculi, have been observed since the 1940's in the rabbit colony maintained at The Jackson Laboratory. Treatment of individual rabbits with obvious clinical lesions using a product containing crystalline penicillin and dihydrostreptomycin caused lesions to heal but venereal spirochetosis persisted in the colony. Clinical and serological responses of rabbits receiving three subcutaneous injections of benzathine penicillin G-procaine penicillin G (either 42,000 or 84,000 IU/kg body weight/week) at 7 day intervals were monitored. Both doses were effective. Lesions healed within 2 weeks of the first treatment. Rapid plasma reagin titers declined markedly or disappeared by the sixth week after the first treatment. Based upon the above findings and results of previous epizootiological studies, a program to eradicate venereal spirochetosis from this enzootically infected colony was successfully undertaken.

Animals↗
PubMed1980

Frequency of congenital abnormalities and of anatomical variations among JAX rabbits.

The frequency of congenital abnormalities and anatomical variations as observed among JAX rabbits is reported. Data were drawn from 32,082 inbred and partially inbred rabbits and 3,208 hybrids from the colony of the Jackson Laboratory over an eight-year period. Data reported here include stillbirths, rabbits dying from natural causes, and those killed for specific experimental regimens. Frequency data are based on the number of abnormalities observed in each category as a function of the total number of animals necropsied. This is approximately 95% of the animals born during the eight-year period and gives the frequency of abnormalities within each category rather than the number of individuals with one or more abnormalities. Anatomical variations have been found in almost all organ systems of JAX rabbits. Their presence adds to our knowledge of the characteristics of these strains, a knowledge that is critical to the understanding of the results of experimental manipulation or for determination of the presence of new mutations. There is considerable between-strain variation. Where frequencies are relatively high, the conditions are either known or suspected to be of genetic origin. Most of the anomalies are not deleterious, or their frequency is so low as to cause no problems within the colony. Hybrid populations have substantially fewer anomalies than do the parental strains. Where frequency is relatively high, it tends to be intermediate between the parental strains.

Animals↗
PubMed1980

Herpesvirus saimiri-induced malignant lymphoma in inbred strain III/J rabbits (Oryctolagus cuniculus).

Four young strain III/J rabbits of both sexes were inoculated with a single dose of prototype partially purified Herpesvirus saimiri (HVS) via IV and IM routes. All inoculated animals had enlarged lymph nodes, and significant levels of antibodies to HVS early, late, and membrane antigens were detectable during the infection. The animals died or were killed and HVS was isolated from the peripheral blood mononuclear cells and the various lymph nodes but not from the kidney. Microscopic examination showed that these animals had poorly differentiated lymphomas. The response of mononuclear cells to PHA from peripheral blood of infected animals showed depressed cell mediated immune responses. Humoral and cellular immunity responses during tumorigenesis were comparable to those reported in nonhuman primates with HVS-induced tumors. Thus, the inbred strain III/J appears to be an inexpensive suitable model for studies of oncogenic herpesvirus-induced cancers.

Animals↗
PubMed1980

The rabbit (Oryctolagus cuniculus) and research on aging.

This review provides background material on the rabbit of interest to scientists engaged in research on aging. It also summarizes some of the recent work using the rabbit in such research. The purpose of this review is to acquaint gerontologists with work primarily in the European literature where the rabbit has been used extensively in research on aging.

Aging↗
PubMed1980

Transplacental teratogenic and carcinogenic effects in rabbits chronically treated with N-ethyl-N-nitrosourea.

Pregnant rabbits of two partially inbred strains, WH/J and IIIVO/J, were given ten consecutive daily ip injections of 10 mg N-ethyl-N-nitrosourea (ENU)/kg dissolved in trioctanoin starting on either day 10, 15, or 18 of gestation. Of 7 WH/J progeny weaned, 3 developed primary renal tumors at 6.8 +/- 0.6 months of age (mean +/- SE). Similarly, of 12 IIIVO/J progeny weaned, 10 developed primary renal tumors at 6.3 +/- 0.6 months of age (mean +/- SE); in addition, 1 fibroblastic osteosarcoma and 5 neurofibromas, some associated with neurilemma cysts, were observed. Renal tumors were nephroblastomas , which appeared to develop within small renal cortical cysts. The frequency of tumor induction for each strain was similar to that in our previous experiments with acute administration of ENU and ethyl-urea plus NaNO2, but the latency period (6.4 +/- 0.5 mo) was almost doubled. In addition, chronic treatment of ENU induced teratogenic effects. In a number of these progeny, a disproportionate stunting or miniaturization was evident, the frequency of which increased with the age of the treated fetuses. In contrast, holes were found in the parietal bones at birth, but with a frequency that decreased with increasing fetal age at time of treatment. No teratogenic effects were observed in the controls.

Animals↗
PubMed1979

Chromosomal homology of rabbit (Oryctolagus cuniculus) linkage group VI with rodent species.

Homologous portions of linkage group (LG) VI in the rabbit Oryctolagus cuniculus, chromosome 8 in Mus musculus, and LG V of Rattus norvegicus have been observed. These linkage groups in Oryctolagus and Mus contain the extension locus (e), where recessive alleles are known in many species. Preliminary linkage data have added new loci to linkage group VI of the rabbit, revised the order and map distances on the linkage map, and by comparison with rodent species have strengthened the homology of LG VI in the rabbit with chromosome 8 of the mouse and with LG V of the rat. LG VI now contains five loci with the following order and intervening map distances: Es-1, Es-2 complex--6.3 +/- 2.1 cM--Est-1, Est-2 complex--18.5 +/- 3.7 cM--e.

Animals↗
PubMed1978

Induction of type C RNA virus from cultured rabbit lymphosarcoma cells.

Type C RNA virus(es) was readily released from primary lymphosarcoma cell cultures of WH/J rabbits after induction with halogenated pyrimidines. The virus contained an RNA-directed DNA polymerase and the p30 structural protein. The rabbit virus RNA-directed DNA polymerase and p30 protein shared antigenic homologies with other mammalian type C oncornaviruses but appear to also possess unique antigenic determinants. Normal rabbit liver contained DNA homologous to a 3H-labeled complementary DNA transcript of the rabbit viral genome, indicating that type C viral genetic information is present in at least the WH/J strain of rabbits.

Animals↗
PubMed1977

Strain differences in response to dietary cholesterol by JAX rabbits: correlation with esterase patterns.

Six strains of genetically defined JAX rabbits were tested for their serum cholesterol levels (total and free) in response to a 0.5% cholesterol diet. Marked differences in response between the 6 strains were found. IIIVO/J and WH/J are low responding strains, X/J and ACEP/J are intermediate responding strains, and OS/J and AX/J are high responding strains. After 4 weeks of the cholesterol diet the total serum cholesterol level of the high responding AX/J strain was about 5-fold greater than the level of the low responding IIIVO/J strain. The esterified/total (E/T) ratio appeared to be higher in the high responding strains, indicating a synergistic effect in the process of atherosclerosis. The response of the individual rabbits to the cholesterol diet was compared with the patterns of serum and liver esterase zymograms. This comparison indicated a correlation of the dietary cholesterol susceptibility with the presence or absence of the esterase zones in the anodal, fast moving region of the gel.

Animals↗
PubMed1976

Evidence for a particle-associated RNA-directed DNA polymerase in rabbit placental and uterine tissues.

A RNA-directed DNA polymerase associated with particles that band at a density characteristic of type C RNA viruses was found in normal rabbit placental and uterine tissues taken during the early stages of gestation. That the rabbit RNA-directed DNA polymerase is distinct from the known cellular DNA polymerases and similar to the RNA-directed DNA polymerase of mammalian type C RNA viruses is shown by column chromatographic characteristics, template primer preferences, molecular weight determination, and an absolute requirement for the divalent cations.

Animals↗