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T M Trischmann

Publications and source records attributed to T M Trischmann.

4 recordsLinked to original sources
PubMed1991

Selection of normal human hematopoietic stem cells for bone marrow transplantation using immunomagnetic microspheres and CD34 antibody.

Complete yet nontoxic removal of tumor cells from autologous marrow grafts has proved difficult. New methods for separating normal stem cells from tumor cells are needed. The CD34+ cells in bone marrow, 1-2% of the low-density leukocytes, include precursors of all lymphohematopoietic lineages and probably also the primitive cells responsible for engraftment. A nontoxic, inexpensive, reproducible, and clinically applicable method for positive selection of CD34+ cells was developed. Paramagnetic microspheres coated with goat anti-mouse IgG1 are used to partition the cells; brief incubation with chymopapain is used to release them from the beads. Chymopapain exposure does not injury colony-forming cells or delay engraftment in rodents. Clinical volumes of bone marrow can be processed rapidly. In pilot experiments, the resulting grafts have a purity of 85-99% CD34+ cells and 40% median recovery of the assayable colony-forming cells. These studies form the background for a Phase I trial of autologous BMT using CD34+ stem cells.

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PubMed1990

Positive stem cell selection--basic science.

Immunologic strategies for removal of malignant cells from autologous marrow grafts by "negative selection" (i.e., "purging") requiring multiple specific monoclonal antibodies for each tumor type. "Positive selection" of marrow stem cells for grafting is a possible alternative strategy, using a monoclonal antibody which selectively recognizes lymphohematopoietic stem cells. The human hematopoietic progenitor cell antigen, CD34, is an integral cell membrane glycoprotein of approximately 115 kD, which has been molecularly cloned and sequenced. Although its function has not been determined, the glycoprotein has been characterized biochemically, including preliminary epitope mapping. Collective results from several laboratories indicate that CD34 monoclonal antibodies (My10, BI-3C5, 12.8, etc.) have the appropriate specificity to warrant testing their utility in positive selection for autologous bone marrow transplantation. First, precursors for all human hematopoietic lineages assayed (including most CFU-GM, BFU-E, CFU-MEG, CFU-EO, CFU-MIX or CFU-GEMM, pre-CFU, CFUBLAST, and terminal transferase+ B [and probably T] lymphoid precursors) are CD34+. Second, only 1.5% (mean) of low density human marrow mononuclear cells express CD34; mature human blood and marrow cells are CD34-. Endothelial cells are the only fixed tissue cells which express CD34. Third, the expression of CD34 in malignancies appears to parallel normal cellular expression: of hematopoietic malignancies, some acute leukemias and chronic myelogenous leukemia blasts are CD34+, but chronic lymphois leukemias, lymphomas, myelomas and non-hematopoietic malignancies are uniformly CD34-. Fourth, it appears feasible to isolate CD34+ cells from clinical marrow harvest samples in large scale, using either columns or immunomagnetic microspheres. Fifth, recent studies in very small numbers of non-human primates and human patients suggest that isolated CD34+ cells include the true hematopoietic stem cell, since transplantation of CD34+ cells, into myeloblated recipients results in at least short-term hematopoietic engraftment. It is anticipated that transplantation of CD34+ marrow cells may have broad applicability in clinical bone marrow transplantation.

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PubMed1986

Trypanosoma cruzi: early parasite proliferation and host resistance in inbred strains of mice.

The extent of parasite proliferation following completion of the first cycle of intracellular replication was significantly higher in CD-1 nu/nu mice and in irradiated mice compared to other, including highly susceptible, mouse strains. A control of parasite proliferation thus occurs in normal mice as early as the first cycle of intracellular replication. The thymus dependency and radiation sensitivity of the early control of proliferation of Trypanosoma cruzi suggest that an immune response to the parasite is involved in the early control of proliferation. The BXH-2 recombinant inbred strain demonstrated an inability to control early proliferation and, 4-5 days after infection, had parasitemias several times higher than those observed in susceptible mouse strains. The BXH-2 strain appears to lack the early control mechanism. When the extent of proliferation of T. cruzi at completion of the first cycle of intracellular replication was compared in inbred strains of mice having varying levels of resistance to the parasite, the extent of proliferation correlated with host resistance, being lowest in the most resistant strains (C57BL/6, SJL) and highest in the most susceptible strains (C3H, A). It is suggested that the mechanism(s) controlling early parasite proliferation may be of primary importance as the basis for host resistance.

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