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Biomedical subjects

P Chandler

Publications and source records attributed to P Chandler.

At least 73 records · Page 4Linked to original sources
PubMed1983

H-Y typing of karyotypically abnormal mice.

It has been proposed that the male-specific transplantation antigen H-Y is the trigger for testis formation (Ohno's hypothesis). We have tested this hypothesis by examining the H-Y status of a number of mice with abnormal or aberrant karyotypes relative to their gonad development. This analysis includes the discussion of published results of XX males carrying the Sxr mutation and XO females, and the presentation of unpublished data from XY females carrying the YPOS or YORB chromosome, XY females carrying Thp on chromosome 17, and a series of mice carrying X-Y recombination products derived from the Y* chromosome. The XX Sxr males have testes and are H-Y transplantation antigen positive; XO females have ovaries and are H-Y negative; mice with X-Y reciprocal recombinant chromosomes resulting from an abnormal Y chromosome show concordance between the presence of testes and the presence of the H-Y antigen. All of these findings are in accord with Ohno's hypothesis. In contrast are our findings that three types of C57BL/6J XY females are H-Y positive, two inheriting a Y chromosome from the mouse species Mus domesticus, either YPOS or YORB, and the other a mutation associated with Thp. Genetic analysis of the inheritance of this paradoxical phenotype indicates that normal testis differentiation involves the interaction of two or three genes, and is not simply a function of a Y-linked gene product. We conclude that H-Y is not the sole Y-linked testis determining gene.

Animals↗
PubMed1983

Enhancement of specific antitumor immunity in mice fed a diet enriched in vitamin A acetate.

Age-matched male CBA mice on a conventional or a vitamin A acetate (VAOAc)-rich diet were immunized with irradiated cloned 3-methylcholanthrene- or Harvey sarcoma virus-induced (McSa-1 or HT3-2.1) sarcoma cells and then challenged with viable corresponding or unrelated (non-crossreacting) syngeneic sarcoma cells. The survival of the specifically immunized mice on the VAOAc diet was significantly prolonged in comparison with all control groups of mice as assessed by using logrank tests. Moreover, the specific immunization markedly decreased the incidence of tumors after the McSa-1 (but not HT3-2.1) challenge in a group of mice on the VAOAc diet (5% tumor incidence) compared with the equivalent group on the control diet (50% tumor incidence). Neither the VAOAc diet nor in vivo immunization alone or combined influenced natural killer cell activity. Specific T-cell-mediated cytotoxicity after in vivo priming and in vitro boosting with sarcoma cells was increased in VAOAc-fed mice. However, the marginal increase in cytotoxicity does not in itself explain the strikingly increased resistance to tumor transplants in preimmunized mice on the VAOAc diet in comparison with preimmunized mice on the control diet. The results indicate that a diet enriched in VAOAc can modify the ability of the immune system of a mouse to respond effectively to tumor antigens and can influence whether a tumor grows or regresses.

Animals↗
PubMed1983

Nonspecific inhibitor of DNA synthesis elaborated by T acceptor cells. I. Specific hapten- and I-J-driven liberation of an inhibitor of cell proliferation by Lyt-1-2+ cyclophosphamide-sensitive T acceptor cells armed with a product of Lyt-1+2+-specific suppressor cells.

Lyt-1+2+ hapten-specific T suppressor cells (Ts) from mice injected and then painted with picryl or oxazolone derivatives produce hapten-specific T suppressor factors (TsF) in vitro. Stimulation by painting with contact sensitizer (which need not be specific) gives rise to Lyt-1-2+, I-J+, cyclophosphamide-sensitive T acceptor cells (Tacc). When the Tacc population is armed with TsF and then is exposed to specific antigen in the context of I-J-controlled determinants (antigen-presenting, haptenized spleen cells and Ts sharing the same I-J subregion), a nonspecific inhibitor of DNA synthesis (nsINH) appears in the supernatant. This inhibitor suppresses the primary DNA synthetic response to concanavalin A, lipopolysaccharide, and alloantigens in both syngeneic and allogeneic lymphocytes. The nsINH is only effective when added to lymphocyte cultures less than 8 hr after the stimulation with concanavalin A. The nsINH, however, affects neither primary nor secondary cytotoxicity in vitro. These data suggest the mouse immune system is capable of selective regulation of the response to specific antigen by the production of nonspecific soluble suppressor factor(s).

Animals↗
PubMed1981

Supposed lamarckian inheritance of immunological tolerance.

The notion that an adaptation acquired during an organism's lifetime can somehow be imprinted on the genome and so become heritable has been faulted by every critical test to which it has hitherto been exposed, but many naturalists have lost their faith in what seems to them to be the all-encompassing explanatory glibness of neo-darwinism. Although this criticism is unfair it is entirely proper that neo-darwinism should be under constant critical scrutiny. Interest was therefore aroused by the claim of Gorczynski and Steele that tolerance of A strain antigens induced in CBA mice by injecting into them (CBA x A/J)F1 spleen and bone marrow cells could be transmitted down the male line. Such a claim is of particular interest because spermatozoa, unlike oocytes, are produced throughout life and might thus conceivably have participated in the mechanism envisaged by Steele as that responsible for the supposed transfer of genetic information from soma to germ plasm. It was claimed that as many as 60% of the progeny of tolerant fathers mated with normal CBA females were unresponsive or hyporesponsive in an in vitro assay in which their spleen cells were tested for reactivity against A/J strain histocompatibility antigens in the cell-mediated lympholysis assay (CML). We describe here our failure to confirm these findings and our inability to extend them by testing the progeny for their reactivity against skin allografts from the tolerance-conferring strain.

Adaptation, Physiological↗
PubMed1981

Immune reactivity of progeny of tetraparental male mice.

Steele and Gorczynski have recently suggested that inbred male mice rendered tolerant at birth to the alloantigens of an H-2 plus non-H-2 incompatible inbred strain can transmit this tolerance or hyporeactivity, as measured in a primary anti-H-2 cytotoxic T-cell test in vitro, to their progeny, born of normally reactive females syngeneic with the males. As a corollary, it might be expected that the progeny of tetraparental males which are tolerant because from earliest fetal development they are chimaeric with respect to all tissues, including haematopoietic cells and germ cells, might in turn be tolerant to the other set of paternal alloantigens. We have now found, on the contrary, that inbred progeny of one component of a tetraparental male showed heightened responsiveness to the other paternal alloantigens.

Animals↗
PubMed1981

A simple micromethod for MLC and CML with low numbers of murine lymph node and peripheral blood lymphocytes.

A fast and simple method is described for the mixed lymphocyte culture (MLC) of low numbers of murine lymph node (LN) and peripheral blood lymphocytes (PBL). Cultures were set up with 1 X 10(4) - 4 X 10(4) responder cells in wells of inverted Terasaki plates where the cells settled at the meniscus of a hanging drop. [3H]thymidine incorporation and 51Cr-release from appropriate allogeneic target cells were determined either directly in the same hanging drop or after cell transfer and serial 2-fold dilutions in new Terasaki plates. Replicate measurements were reproducible by both methods. Responder and stimulator cell surface antigens could also be tested by addition of antisera with complement, either at the initiation or at the effector stage of culture. Since culture volumes were only 15 microliter, almost negligible quantities of antisera were required. The method was thus particularly valuable for testing with antisera of limited availability. Examples are given where inclusion of an anti-responder alloantiserum plus complement on day 0 of the MLC eliminated the day 4 cytotoxic response, and where treatment of cytotoxic effector cells with alloantiserum plus complement for 1 h prior to the 51Cr-release assay eliminated the effector cell activity.

Animals↗
PubMed1979

Use and functional properties of peripheral blood lymphocytes in mice.

Peripheral blood lymphocytes (PBL) were isolated and examined for their ability to respond in vitro to H-2 and H-Y antigens and also to hapten conjugated syngeneic cells. In addition, these lymphocytes were tested as antigen and target cells in in vitro mixed lymphocyte reaction and in chromium release cell mediated lympholysis respectively, as well as serving as targets for the H-2 typing of chimeric mice. Two methods were used to isolate the lymphocytes: a density gradient separation and a double water lysis technique. PBL, prepared by either method compared favourably with splenic lymphocytes in all aspects of anti-H-2 cytotoxicity but could not be used as responder for anti-H-Y cytotoxicity. In addition a method has been developed using PBL as targets for H-2 typing of both allophenic and irradiation chimeric mice. The small numbers of cells required for each of these procedures allows for the preselection of suitable mice and/or multiple experimental determinations on individual mice.

Animals↗
PubMed1978

Cross-reactive cytotoxic responses. H-2 restricted are more specific than anti-H-2 responses.

Cross-reactive T-cell cytotoxicity is seen when cytotoxic responses are generated in mixed lymphocyte cultures either between mouse strans which differ at the major histocompatibility complex, H-2, or between H-2b mutant strains and the strain from which they were derived. This cross-reactivity can be measured with [51Cr] labeled target cells from a number of different H-2 haplotypes, and the pattern of cross-reaction indicates that the target antigens are unlikely to be any of the serologically defined public specificities. In contrast, the specificity of H-2 restricted cytotoxic responses, such as that to the male-specific antigen, H-Y, is exquisite, and male cells from strains of mice carrying H-2 haplotypes other than the responder have never been found to act as appropriate targets. The contrast between the specificity of anti-H-2 and H-2 restricted responses may argue for a greater idiotypic homogeneity of the cells makiing H-2 restricted responses, and the greater specificity of these responses may be necessary for their biological function.

Animals↗
PubMed1976

Micromethods for induction and assay of mouse mixed lymphocyte reactions and cytotoxicity.

A new method in which induction of mixed lymphocyte responses and cytotoxicity can be performed under identical conditions is described. This enables the investigation of the relationship between MLR and cytotoxicity. A micro method for the 51Cr release assay for cytotoxicity is described using both mitogen-induced blasts and tumors as target cells. Under the conditions used data obtained is suitable for linear regression analysis, enabling quantitative comparisons to be made.

Animals↗
PubMed1976

Disseminated intravascular coagulation in nonocclusive mesenteric ischemia: the lack of specificity of fibrin thrombi in intestinal infarction.

The significance and frequency of fibrin thrombi (FT), the pathological hallmark of disseminated intravascular coagulation (DIC), in ischemic intestine were analyzed in a retrospective study of the infarcted bowel of patients with occlusive mesenteric ischemia (OMI) and nonocclusive mesenteric ischemia (NOMI). Representative intestinal sections were studied from 10 patients with NOMI of the small and/or large bowel and 12 patients, with OMI of varied etiology. Three patients with inflammatory bowel disease and 1 patient with DIC and bowel necrosis were also studied. Routine hematoxylin and eosin stains for fibrin were prepared for each specimen. The number of FT was quantitated. FT were identified in each of the 10 cases of NOMI; however in only 2 were they prominent. FT were identified in 6 of the 12 cases of OMI and in 4 of these 6 they were a prominent feature. Rare FT were present in the cases of inflammatory bowel disease and did not correlate with the inflammatory process. No FT were present in the intestinal sections of the DIC case. FT are a nonspecific feature of necrosis and can be identified in both occlusive and nonocclusive ischemic bowel disease. Their presence in the intestine of NOMI therefore cannot be used to implicate DIC as the primary cause of this entity.

Blood Platelets↗