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Biomedical subjects

W Müller-Ruchholtz

Publications and source records attributed to W Müller-Ruchholtz.

At least 109 records · Page 6Linked to original sources

Covalent conjugates of monoclonal antibody and cobra venom factor mediate specific cytotoxicity via alternative pathway of human complement activation.

Because of lack of unspecific toxicity autologous serum is the optimal source of complement for in vitro cell depletion in human bone marrow transplantation. Covalent binding of cobra venom factor to an antibody leads to a specific complement activating conjugate with cytolytic potential independent of the capacity of the antibody to fix complement itself. Therefore this conjugation allows the use of various sera, including human as the source of complement. The kinetics of cobra venom factor-initiated cytolysis is compatible with in vitro treatment of bone marrow prior to transplantation.

Antibodies, Monoclonal

Comparison of gamma-interferon and alloantigen-induced T cell factors in the induction of MHC class II antigen expression and in the modulation of the immunogenicity of lymphocyte-free rat bone marrow.

In a rat model, we compared the effects of various soluble products released by T cells, such as the unspecifically acting gamma-interferon or the newly detected alloantigen-induced factors that specifically act on nonlymphoid, hemopoietic bone marrow cells. We found two types of reactivity patterns with regard to the induction of MHC class II antigen expression on these cells. The very same patterns could be demonstrated when we investigated the modulation of their stimulatory capacity, i.e., their immunogenicity in a T proliferation assay. These findings are discussed in relation to the increasing incidence of immunologically mediated graft rejections in clinical bone marrow transplantation following T cell purging.

Animals

Transplantation of aortic and pulmonary allografts, enhanced viability of endothelial cells by cryopreservation, importance of histocompatibility.

Fresh heart valve allografts were preserved at 4 degrees C for 14 days, cryopreserved and stored for 63 days, and studied for endothelial viability and antigenicity, in order to obtain some information on the immunobiological status of allografts before transplantation. The surgical technique described by Ross for subcoronary position is preferred and briefly outlined. Four explanted incompatible allografts were studied by light and scanning electron microscopy and immunohistochemistry to assess the immunological reactions and tissue changes that occurred between 9 days and 16 weeks postoperatively. Valve leaflet motion and opening velocities were studied by echocardiography postoperatively to establish a baseline with which to distinguish early leaflet degeneration. Distensibility of the aortic annulus was studied postoperatively by supraaortic angiography to justify one of the goals of reconstruction of the aortic root with allografts. Antibiotic preserved allografts at 4 degrees C showed no viable endothelial cells after 8 days while the cryopreserved allografts demonstrated a high rate of viable endothelial cells capable of expressing surface antigens (HLA class I and II). Although the valve explants showed focal mononuclear cell infiltrations with T-lymphocytes, the allografts healed in place. The "classic" findings of rejection could not therefore be demonstrated. In summary, cryopreserved valve allografts, like the fresh, are antigenic. It is therefore recommended to use compatible valve grafts, when possible, which might be a positive step to improve the functional longevity of valve allografts. Immune response after valve allograft transplantation does not cause acute valvular dysfunction but rather chronic tissue changes which might lead to early degeneration of the allograft. The opening velocities of preserved aortic and pulmonary allografts were normal at 3-4 years postoperatively irrespective of histocompatibility. Echocardiography might be a useful tool to detect early degenerative changes of incompatible valve leaflets. The aortic root is distensible after allograft transplantation.

Adolescent

Role of lymphocytes in the modulation of the immunogenicity of bone marrow: a rat model.

In a rat model we describe the role T lymphocytes play in the immunogenicity of bone marrow. Mainly they modulate the MLC-like stimulatory cell potential and the MHC class II antigen expression of nonlymphoid bone marrow cells via the release of newly detected specific soluble factors and immunologically unspecific ones. These findings are discussed in relation to the graft rejection encountered in clinical bone marrow transplantation following certain T depletion protocols.

Animals

Graft-versus-host reaction in small bowel transplantation and possibilities for its circumvention.

To describe GVHR in small bowel transplantation and its underlying mechanisms and to find methods for circumventing that response, accessory small bowel transplantation was carried out in the rat model. Animals not treated with cyclosporine, irradiation, or removal of the mesenteric lymph nodes of the graft died within 22 days postoperatively due to graft versus host disease. Mesenteric lymph nodes of the graft and recipient spleen and peripheral lymph nodes showed strong immunologic stimulation histologically and high antihost T-cell-mediated cytotoxic antihost reactivity. Seventy-one percent of the animals that had received 15 mg of cyclosporine per kilogram body weight orally survived 150 days after transplantation. After donor irradiation with 50 rads, 77 percent of the recipients survived 120 days. After microsurgical removal of the mesenteric lymph nodes of the graft, 89 percent survived 120 days. We conclude that GVHR plays an important role in small bowel transplantation and that the experimental regimens of donor, graft, and recipient treatment described herein have proved their efficacy for circumventing GVHR.

Animals

Immune reactivity after high-dose irradiation.

Immune reactivity after total-body irradiation was investigated in rats using skin graft rejection as the indicator system. After sublethal irradiation with 10.5 Gy (approximately 50% lethality/6 weeks) the rejection of major histocompatibility complex allogeneic skin grafts was delayed significantly compared with nonirradiated control animals (28 versus 6.5 days). In contrast, skin grafts were rejected after 7.5 days in sublethally irradiated animals and 7 days in lethally irradiated animals if additional skin donor type alloantigens--namely, irradiated bone marrow cells--were given i.v. either simultaneously or with a delay of not more than 24 hr after the above conditioning regimen. These reactions were alloantigen-specific. They were observed in six different strain combinations with varying donors and recipients. Starting on day 2 after irradiation, i.v. injection of bone marrow gradually lost its effectivity and skin grafts were no longer rejected with uniform rapidity; skin donor marrow given on days 4 or 8 did not accelerate skin graft rejection at all. These data show that for approximately 1-2 days after high-dose total-body irradiation rats are still capable of starting a vigorous immune reaction against i.v.-injected alloantigens. The phenomenon of impaired rejection of skin grafted immediately after high-dose irradiation appears to result from the poor accessibility of skin graft alloantigens during the early postirradiation phase when vascularization of the grafted skin is insufficient.

Animals