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Biomedical subjects

S D Horowitz

Publications and source records attributed to S D Horowitz.

30 records · Page 2Linked to original sources
PubMed1978

Deoxyadenosine triphosphate as a potentially toxic metabolite in adenosine deaminase deficiency.

The inherited deficiency of adenosine deaminase (adenosine aminohydrolase; EC 3.5.4.4) activity in humans is associated with an immunodeficiency. Some of the immunodeficient and enzyme-deficient patients respond immunologically to periodic infusions of irradiated erythrocytes containing adenosine deaminase. It has been previously reported that erythrocytes and lymphocytes from immunodeficient ane enzyme-deficient children contained increased concentrations of ATP, and in the one child studied after erythrocyte infusion therapy, the intracellular level of ATP diminished. Using high-pressure liquid chromatography that resolves ATP and 2'-dATP, we have observed greater than 50-fold elevations of dATP in the erythrocytes of immunodeficient, adenosine deaminase-deficient patients but not in the erythrocytes of an immunocompetent adenosine deaminase-deficient patient. The erythrocyte dATP in two unrelated adenosine deaminase-deficient, immunodeficient patients disappeared after infusion of normal erythrocytes. We propose that deoxyadenosine, a substrate of adenosine deaminase, is the potentially toxic substrate in adenosine deaminase deficiency, and that the mediator of the toxic effect is dATP, a recognized potent inhibitor of ribonucleotide reductase.

Adenine↗
PubMed1978

Murine macrophage-lymphocyte interactions: scanning electron microscopic study.

Light and scanning electron microscopic observations revealed murine macrophage-lymphocyte interactions involving the initial contact of peritoneal, spleen, or thymus lymphocytes with peritoneal macrophage processes or microprocesses followed by clustering of lymphocytes over the central nuclear area of the macrophages. Lymphocyte-lymphocyte clustering was not observed in the absence of macrophages. Attachment and subsequent clustering appeared not to require the presence of serum or antigen; the attachment of allogeneic or xenogeneic lymphocytes was comparable to that seen in the syngeneic system, but central clustering of these lymphocytes failed to occur. No attachment or clustering was observed when thymic lymphocytes were cultured with thymus derived fibroblasts rather than with peritoneal macrophages. Lymphocyte attachment to immune, antigen-activated, syngeneic macrophages occurred more rapidly than that to normal unstimulated syngeneic macrophages; however, lymphocytes attached to the "activated" macrophages appeared to be killed by a nonphagocytic mechanism. A similar increase in the rate of lymphocyte attachment to macrophages occurred in the presence of migration inhibitory factor. Subsequent lymphocyte clustering on macrophages was observed in the migration inhibitory factor-stimulated cultures. In addition, lymphocyte-macrophage interactions similar to those in vitro were observed to occur in vivo on intraperitoneally implanted cover slips.

Animals↗
PubMed1975

Treatment of severe combined immunodeficiency with bone-marrow from an unrelated, mixed-leucocyte-culture-non-reactive donor.

A 7-month-old boy with severe combined immunodeficiency had no relative who was a suitable bone-marrow donor as determined by mixed-leucocyte-culture (M.L.C.) testing. In the general population an M.L.C.-nonreactive, unrelated donor was found among individuals who were identical with our patient at the Four locus. Following a bone-marrow transplant this child showed signs of rapid immunological reconstitution and only a mild graft-versus-host reaction. Unfortunately, the child died 31 days post-transplantation of cytomegalovirus infection. The findings support the hypothesis that matching for lymphocyte-defined antigens among unrelated individuals will permit successful immunological reconstitution.

Bone Marrow Cells↗