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Chromatographic comparisons of heterotic rat liver histones.

Chromatographic comparisons of histones isolated by acid extraction of liver chromatin preparations from F344 inbred rats and their paternal heterotic F344 X H hybrid progeny reveal the presence of a number of age-and line-specific nonhistones also extractable in acid. The patterns of the core histones (H2A, H2B, H3, and H4) remain relatively constant during development, while histone H1 shows unusual chromatographic properties in the 30- and 35-day hybrid preparations. In general, the complexity of the nonhistone fraction decreases as the animal ages. Such variations may be a reflection of a prelude to altered genetic activity in organisms undergoing growth and development at different rates, and may have significant implications for transcriptional processes.

Age Factors

Electrophoretic comparisons of liver chromatin proteins isolated from heterotic rats during postweaning development.

Electrophoretic comparisons of histones and other acid-extractable chromatin proteins isolated from the livers of growing F344 inbred rats and a heterotic paternal hybrid derived by crossing F344 males with Holtzman females reveal significant heterogeneity among a class of nonhistone components soluble in acid. These variations appear to be age and line specific and show more variation in the inbred than the hybrid. Comparisons of the acid-insoluble nonhistone proteins by sodium dodecylsulfate gel electrophoresis reveal significant quantitative changes in a 28,600 dalton polypeptide present in large quantities at 30, 35, and 50 days of age in the hybrid and at 40 and 45 days only in the inbred. Other minor variations were noted in a class of proteins of 40,000--45,000 molecular weight and in those of very high molecular weight (100,000-200,000). Such variations could be a reflection of or prelude to changes in genetic activity and could ultimately be important in the control of growth patterns of developing heterotic animals.

Aging

Morphological reaction in transplanted small intestines using immunogenetically defined rat strain combinations.

From the inbred rat stains F344, LEW and Brown-Norway (BN), the following combinations were formed: syngeneic (LEW--LEW), weakly allogeneic (F344--LEW) and strongly allogeneic (BN--LEW). A small intestine segment was transplanted using the by-pass technique; after 10 days the graft was removed and histologically investigated. The strongest rejection was found in the lymphatic tissue and the epithelium of the small intestinal transplant. The immunogenetical difference is significant for the survival of the graft: the greater the immunogenetical difference between donor and host, the more severe the morphologically demonstrable rejection reaction.

Animals

The avidity of IgM antibody in high and low responder rats.

This study examined IgM antibody produced by highly responding ACI and poorly responding F344 rats follwing immunization with poly(Glu52Lys33Tyr15) or poly(Glu52Lys33Tyr15) aggregated with methylated bovine serum albunim (MeBSA). The ACI rats produced both IgM and IgG plaque-forming cells (PFC) following immunization with either form of antigen. The F344 rats did not respond to unaggregated poly(Glu52Lys33Tyr15), but they produced significant amounts of IgG PFC and extremely small amounts of IgM PFC after immunization with poly(Glu52Lys33Tyr15)/MeBSA. Both high and low responder rats had similar kinetic profiles of IgM antibody production, and this antibody had nearly identical avidity in both strains with no evidence for any maturation in avidity. thus, one of the genetic defects in the antibody response to poly(Glu52Lys33Tyr15) is an inability of the F344 strain to produce large amounts of IgM in response to this antigen.

Animals

Micro mixed hemadsorption assay--a sensitive method for detecting antibodies against tumor-associated antigens.

Antibodies against methylcholanthrene (MCA)-induced sarcomas in Fischer (F344) rats were detected by a modified micro mixed hemadsorption (MHA)-assay. The assays detected anti-tumor antibodies as titers up to 1 : 320 in sera from hyperimmunized rats and at titers up to 1 : 160 in sera from rats bearing a 5-8 cm3 progressively growing tumor. MHA-titers decreased when sera were absorbed with sarcoma cells prior to MHA-assays. IgG antibodies in sera from tumor bearing rats showed titers of 1:20 and 1:5. These anti-tumor sera formed rosettes on the corresponding sarcoma cells as well as other sarcomes induced by MCA in F344 and Lewis strain rats tested. The assay was modified for a micro technique using a microtest plate (No. 3034, Falcon, CA). This modification yielded as assay requiring only 10 microliter of test sera. The test is quantitative and highly sensitive and results are reproducible. Several critical factors which influence test results in this assay were examined.

Animals

Chronic necrotizing mastitis in rats caused by Pasteurella pneumotropica.

Sixty-one of 2500 F344 rats were observed to have one to three enlarged and firm mammary glands. Pasteurella pneumotropica was isolated from all affected mammary glands. It was also routinely isolated from the feces of all cages and from the oral cavity of rats up to 6 weeks old, but not from the oral cavity of rats over 4 months of age. The organism was not isolated from clinically normal lactating mammary glands. Histopathological diagnosis of affected glands was chronic necrotizing mastitis.

Animals

The kinetics of IgG and IgM antibody-forming cells in ACI and F344 rats immunized with poly(glu52lys33tyr15).

The cellular kinetics of antibody production in high and low responder rats immunized with poly(Glu52Lys33Tyr15) or with poly(Glu52Lys33Tyr15)/MeBSA were characterized: serum antibody and IgG and IgM antibody-forming cells in the spleen and in selected lymph nodes were assayed in male and female rats following immunization by several routes. Aggregation of the antigen with MeBSA enabled the poorly responding F344 rats to produce antibody, which was almost exclusively IgG. High responder ACI rats, under the same conditions, produced antibody of both IgG AND IgM classes. These data suggest that in low responders one defect, possibly at the T-cell level, can be overcome by aggregation but that a second defect, involving the regulation of IgM production, still exists.

Animals

Regurgitation and choke in rats.

Male and female F344 rats choked on fecal pellets and regurgitant during the course of two long-term experiments. Each study involved feeding standard and high bulk diets containing 10% wood cellulose or 10% chrysotile asbestos fiber. Choke deaths occurred at all stages of the experiments. A total of 36 of 774 (4.6%) rats in the two studies died of choke. Females died of choke more frequently (26/382 or 6.8%) than did males (10/392 or 2.6%). Rats on high bulk diets were affected more frequently (33/571 or 5.8%), especially those on 10% asbestos diet (26/311 or 8.4%, than rats consuming standard diet (3/190 or 1.6%). The reason for the difference between females and males was not determined. Although choke may be related to some characteristics of high nonnutritive bulk feed fed in pellet form, the higher risk for females even on standard diet (3/95 or 3.2%) than for males (0/95) indicated that more than one factor operated in the etiology of these events.

Airway Obstruction

The effect of cyclophosphamide and methotrexate on the 'field effect' or unresponsiveness observed in the rat and mouse GvHR.

The Field effect is the decreased biological response to a second challenge in the graft versus host reaction (GvHR). Treatment of recipeint rats or mice during the initial GvHR by methotrexate or cyclophosphamide effected the secondary unresponsivienss. Methotrexate and cyclophosphamide demonstrated different temporal responses indicating different mechanisms of their immunosuppresdive activities.

Animals

The effect of neonatal thymectomy on the induction of autoimmune orchitis in rats.

The objective of these experiments was to determine the effects of neonatal thymectomy on the induction of experimental autoimmune orchitis in inbred rats of the Fischer 344 and Lewis strains. It was found that thymectomy alone in Lewis rats, and thymectomy followed by immunization with testicular extract in both Lewis and Fischer 344 rats, led to the development of autoimmune orchitis, as indicated by decreased testes weights, increased serum spermagglutinating antibody titers and histopathological changes in the testes. These data indicate that rats of the Lewis strain are genetically predisposed to the development of autoimmune orchitis, and thymectomy alone leads to active manifestations of the disease, which are further enhanced by subsequent immunization with testicular extract. In Fischer 344 rats, thymectomy followed by immunization leads to indications of early signs of experimental autoimmune orchitis. This is in contrast to experimentally induced autoimmune diseases in other model systems, where previous investigators have reported that thymectomy lessens or prevents induction of autoimmune disease. It is suggested that these differences may be related to the timing of thymectomy with regard to differences in the time of appearance of sperm antigens (at puberty) as compared to pre-natal and early neonatal appearances of other autoantigens.

Animals