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Effect of BCG on alloimmune cell-mediated cytotoxicity in (C57BL/6Jfemale x A/Jmale)F1 mice. II. Correlation with BCG activity in syngeneic tumor systems.

The effectiveness of selected BCG regimens to produce an activation of cell-mediated cytotoxicity (CMC) in an allogeneic tumor system was compared with its ability to cause tumor regression in syngeneic tumor systems. In the tumor system selected in both inbred LEW rats and inbred C57BL/6J and (C57BL/6Jfemale x A/Jmale)F1 mice, a correlation was observed in that BCG treatments that caused marked CMC activation in the allogeneic tumor systems also effectively caused tumor regression and increased animal survival in syngeneic systems. It was concluded that the allogeneic CMC reaction can be used to predict the capacity of BCG to cause tumor rejection.

Animals

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

Preferential synthesis of IgE reaginic antibodies in rats immunized with alum-adsorbed antigens.

The reaginic antibody response to alum-precipitated ovalbumin (OA) and the dialyzed water-soluble extracts of ragweed (DWSR) and Alternaria tenuis (DWST) in several strains of rats appeared to be wholly an IgE response. There was no evidence of a heat-stable (IgGa) antibody to OA, DWSR and DWST in the sera of the rats immunized with these antigens suspended in alum. Wistar-Furth and Lew inbred and hooded outbred rats produced comparable amounts of reaginic antibody after immunization with DWST, but BN inbred rats failed to generate a reaginic response to this antigen. The amount of antigen-induced histamine release from rat peritoneal mast cells did not always correlate with the level of circulating IgE-specific antibody.

Adsorption

Allogeneic corneal grafting in inbred strains of rats. Histology of graft reaction.

Histological studies of interlamellar keratoplasty in different inbred strains of rats (CAP, LEW) without additional sensitization--i.e. first-set reactions--are described. The corneas of 65 eyes, after allogeneic or syngeneic grafting, were examined from the 3rd to the 90th day--every 2nd day at the beginning of the reaction and later every 5th day. After syngeneic grafting (LEW leads to LEW) a non-specific healing-reaction (only slight vascularization of the graft bed, edema, granulocytic infiltration) reached its climax on the 6th day and subsided by the 10th day. After allogeneic grafting (CAP leads to LEW; RtH-1-incompatible) the non-specific-healing reaction progressed into a second phase, namely the specific reaction: increasing infiltration of the host cornea and the graft with small lymphocytes, blast cells and macrophages, directly followed by severe vascularization, reaching its climax about the 14th day. A third, phagocytic phase succeeded the infiltration leading to elimination of the donor cells, but leaving the donor stroma undamaged. All these alterations had almost completely disappeared after 35 days. Thus, the corneal allograft reaction is discussed as a typical immunological reaction leading to the destruction of transplantation-antigen-bearing cells and permitting observation of the different reaction phases more clearly than in most other tissues.

Animals

[Lymphocyte subpopulations in adjuvant arthritis of rats. Effects of corticoids and gamma irradiation].

Experimental model of human chronic inflammatory arthritis, adjuvant arthritis may be induced only in several strains of inbred Rats: it is well developed in LEW and practically absent in WAG. After adjuvant injection, the PHA-stimulable lymphocytes subpopulation quite disappears from the blood, if polyarthritis is well developed. These cells are probably capted in the tissues implicated in immunological conflict. On the contrary, the ConA-stimulable subpopulation is enhanced in both strains after adjuvant injection, earlier and more intense in WAG than in LEW and that phenomenon is probably linked to a stimulation of suppressor T lymphocytes. Treatment with prednisone or gamma rays inhibits partially and delays the appearance of arthritis in LEW, acting essentially on ConA-stimulable subpopulation.

Adjuvants, Immunologic

Studies of some inflammatory and immunological responses of different strains of rat.

Differences were observed in the severity of AA in four inbred strains of rats. The interindividual correlation of the primary and secondary lesions showed an inverse relationship between the gravity of the primary and secondary lesions in the LEW and LE strains. WAG strain appeared to be the lowest responder in the intensity of the primary and secondary oedema in AA and in carrageenan oedema. This is in agreement with the low vascular permeability of this strain after PGE2 injection. When the values of the immunological tests in the individual strains (LE, WAG, LEW) were compared it was found that there is a reciprocal inverse relationship between them and the intensity of the secondary lesion. It follows from our results that the induction of AA requires very precise conditions, indicating that they might depend both on a critical state of immune reactivity and on the action of the pharmacologic mediators.

Animals

Mercuric chloride-induced anti-glomerular basement membrane antibodies in the rat: genetic control.

Mercuric chloride induces anti-glomerular basement membrane antibodies in the Brown-Norway rat. Various other inbred rat strains (Lewis, Wistar AG, August, PVG/c) were not found to be able to produce such antibodies under the same experimental conditions. Hybrids (F1, F2 and F1 x LEW) were bred from Brown-Norway and Lewis rats and injected with mercuric chloride. It has been demonstrated that the induction of anti-glomerular basement membrane antibodies by mercuric chloride in these crosses is under genetic control. The response was found to depend on two or three genes one of which was H-1-linked. The negative results obtained with L.BN congenic rats were in complete agreement with this conclusion.

Animals

Lens-induced uveitis: further immunological studies in an experimental model.

Inbred rats have been studied to determine under what circumstances sensitization will or will not induce uveitis. After 50 days of biomicroscopic follow-up and histologic evaluation of 119 eyes the following was found in black hooded CAP-rats (RtH-1c) presensitized to eye, liver or kidney (guinea pig): 1. Alterations only following additional damage to their own tissue by lens discission plus iridotomy 2. As the case of lens-induced uveitis in humans, alterations after the disappearance of traumatization reaction in the form of protein-rich exudate clinically and an accumulation of round cells in the anterior uvea, surrounding the lens and retinal vessels histologically 3. Dependence of these alterations on sensitization by xenogenic tissue 4. Dependence of the alterations on the animal strain, i.e. absence in albino LEW (RtH-1(1)).

Animals

Alloantigen expression of a rat Moloney sarcoma.

Cells of a brown Norway (BN) rat Moloney sarcoma (MST) failed to express certain BN alloantigen specificities and bound only about 30-50% the amount of labeled alloantibody bound by normal BN spleen cells. MST cells lacked antigen specificities shared by BN and WF rats, but expressed some of the antigen shared by BN and AUG rats. Further loss of alloantigens that occurred with prolonged in vitro culture was associated with reduced virulence of MST cells for syngeneic hosts and with increased expression of tumor-associated antigens. The LEW rats, which are resistant to MST cells, might have rejected the tumor on the basis of factors other than Ag-B antigens.

Animals

[Is permanent survival of kidney allograft receivers in weak histo-incompatible combinations dependent on enhancement?].

To study the immunological status of indefinitely surviving recipients of histocompatible (minor histoincompatible) allografts we transplanted Fi or (Fi x LEW)F1-kidneys to LEW-rats. At the same time bilateral nephrectomy was performed. To examine the cellular immune response we carried out local GvHR, microcytotoxicity assay and allorosette-formation test with recipient cells. We also studied lymphocytotoxins in the serum of recipients. To detect a blocking serum factor we used allorosette-formation inhibition test and microcytotoxicity assay. A blocking serum factor could not be found. In spite of stimulation with donor specific skin graft the cellular immune response of prolonged surviving recipients was inhibited. Our results suggest that prolonged survival of minor histoincompatible renal allograft recipients was caused by suppression of cellular immune response.

Animals

Quantitative studies on the tissue distribution of Ia and SD antigens in the DA and Lewis rat strains.

The tissue distribution of major histocompatibility complex (MHC) antigens in the DA and Lewis (LEW) strains was studied using LEW anti-DA and DA anti-LEW alloantisera. Quantitative absorption analyses were used with quantitative binding assays for SD and Ia antigens. Initial screening showed that the LEW anti-DA serum contained significant amounts of antibodies against both Ia and SD antigens. On the other hand, the DA anti-LEW serum seemed to be directed almost entirely against Ia antigens, and it was not possible to set up assays for SD antigens in the LEW strain. The most surprising finding was the presence of large amounts of Ia antigen on the kidneys of both the DA and LEW strains, one kidney containing as much Ia antigen as half a spleen. Kidney also contained large amounts of SD antigen. Liver had large amounts of SD, but very little Ia. Heart had only small amounts of both SD and Ia. The relevance of these findings to transplantation of the kidney, liver, and heart are discussed. The other tissues studied were brain, spleen, lymph node, thoracic duct lymphocytes, bone marrow, thymus, RBC, and platelets. The most interesting findings were the presence of relatively large amounts of SD antigens on DA RBC, and small amounts of Ia on the thymus and bone marrow.

Animals

Comparison of the haplotypes of the major histocompatibility complex in the rat. III. Two difficult haplotypes: H-1h (Ag-B12) in the HW strain and Ag-B13 (H-1m) in the MNR/N strain.

Two haplotypes which posed difficult problems in serological identification, those of the HW and MNR/N strains, were studied. The HW strain was originally described as a unique haplotype (H-1h), but breeding difficulties precluded its detailed serological analysis. The red blood cells of the HW strain agglutinate weakly and cross-react with antisera to the Ag-B8 group. Anti-HW antisera cross-react strongly with LEW, ACI and WKA, but absorption with these strains did not produce an adequate typing serum. By judicious selection of recipients, however, an appropriate typing reagent could be made; a particularly useful one was (BUF X MR)F1 anti-HW absorbed with WKA red blood cells. The HW haplotype segregated appropriately in a (DA X HW)F2 population. The HW strain is a low responder to poly(Glu52Lys33Tyr15). The H-1h haplotype of this strain was designated Ag-B12. The MNR/N strain had not previously been studied serologically, although its MLR type had been defined as H-1c (MLR-5). Antisera to MNR/N cross-reacted strongly with the H-1a,b,d,f haplotypes, but MNR/N red blood cells agglutinated only weakly with many antisera. An operationally monospecific reagent antiserum to the MNR/N haplotype could not be made. The uniqueness of the MNR/N haplotype was shown by F1 tests with LEW.1A, LEW.1D and LEW.1F, by various serological analyses, including production of antisera against MNR/N and in the MR strain; by segregation studies with (LEW X LEW.1D)N5 and (DA X DA.MNR)N4 segregating back-cross populations, and by grafting skin from (DA X DA.MNR)N4 homozygous and heterozygous animals to DA recipients. The MNR/N strain is a high-responder to poly(Glu52Lys33Tyr15). The MNR/N haplotype of this strain was designated Ag-B13 (H-1m). The data led to the working hypothesis that the MNR/N strain may be a recombination between the A region of H-1d and the B region of H-1c. In addition, the H-1d private specificity at the A region was probably lost by a deletion mutation which left the main complex of public specificities intact.

Animals

Specificities in natural cell-mediated cytotoxicity by the cross-competition assay.

The cross-competition assay was applied to natural cell-mediated cytotoxicity in human, mouse and rat systems. The results showed that what appeared to be non-selective effects of natural cytotoxicity were in fact highly specific. Each effector suspension included natural effector cells (N cells) that recognized and reacted specifically with many different antigens on target cells, resulting in overall non-selectivity. The specificity of the reaction for each target cell was demonstrated by the selective inhibition of natural cytotoxicity achieved when competitor cells sharing antigens with the target cell were added. Sharing of common target antigens was demonstrated by selective cross-inhibition which was then used to investigate antigens on target cells.

Animals

Molecular bases for the difference in the potency of myelin basic protein from different species in Lewis rats.

The results of this study define the chemical bases for the difference in the encephalitogenic potency reported for the bovine and guinea pig myelin basic proteins. Studies with synthetic peptides showed that the sequence of peptide S53, H-Ser-Gln-Arg-Ser-Gln-Asp-Glu-Asn-OH, which is native to the guinea pig basic protein, is the minimum amino acid sequence necessary for inducing EAE in Lewis rats. The results of this study further showed that specific sequence modifications rendered the native bovine sequence highly encephalitogenic.

Amino Acid Sequence

[The effect of donorspecific antigen type for active enhancement of renal-allografts in the histoincompatible inbred rats (author's transl)].

49 kidneys of male LBNF1-rats were transplanted into male Lewis-rats. BN-rats were used as a source of antigen. Control animals survived 16.1 +/- 1.8 days. 5 recipients were preteated with donorspecific living cells, 7 with semisoluble and 5 with low dosage of soluble antigen. The living cell-pretreatment showed the best effect for the active enhancement, the soluble antigen the least. The pretreatment with 6 mg protein/kg bw. caused the sensibilization of recipients. At the time of transplantation lymphcytotoxic antibody titers were detected in all recipients with pretreatment of living cells, but no titer in other groups. Renal allografts with elevated postopertive titer were rejected rapidly.

Animals

Serum histamine levels following administration of ultrastructural tracers in three strains of rats.

Intravenous administration of the electron-opaque tracer ferritin resulted in substantial elevation of serum histamine levels in both the Munich--Wistar and Wistar-Furth strains of albino rats. Lewis rats were unaffected. Similarly, infusion of the non-protein tracer dextran was followed by greatly elevated serum histamine concentrations in Munich-Wistar and Lewis, but not in Wistar-Furth, rats. In sharp contrast with these results were those obtained using the tracer polyvinylpyrrolidone (PVP). PVP infusion caused no elevation of serum histamine levels in any of the rat strains studied. Caution in the use of such tracers is thus advised, since serum histamine concentration affects vascular permeability. Careful matching of ultrastructural tracer and strain of experimental animal is prerequisite in permeability studies.

Animals

Interoceptive conditioning through repeated suppression of morphine-abstinence. II. Relapse-testing.

The reinforcing properties of etonitazene, both conditioned and unconditioned, were measured in rats that had received saline only by continuous intravenous infusion ("saline" group) and in two groups of rats that had been physically dependent on morphine to equal degrees (and presumably had developed equal degrees of tolerance to morphine): one by once daily passive intravenous injection of morphine ("injection" group) and the other by passive continuous intravenous morphine infusion at the same daily doses for approximately the same number of days ("infusion" group). Prior to passive saline and morphine administration, all rats were trained to press right- and left-sided levers for water reinforcement from 1600 to 0800 hrs to a not more than 60-40 split, and these and other measures ("baselines") were repeated after recovery from the early (acute) morphine-abstinence syndromes. Then etonitazene, 5 micrograms/ml, was substituted for water on the nonpreferred side and all measures were repeated from 1600 to 0800 hrs once every two weeks for 20 weeks (10 "relapse" tests). It was postulated that the daily cycles of morphine-abstinence and suppression of abstinence in the injection group only would generate latent interoceptively conditioned reinforcing properties of morphine because of conditioning of suppression of abstinence to the concomitant internal sensorial effects of morphine, which would persist after morphine withdrawal and be transferred to the internal effects of another opioid, etonitazene. It was found that across the first nine relapse tests, the injection group consumed significantly more etonitazene than the infusion group, while there were no significant differences in water consumption.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals