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Biomedical subjects

J J Wielenga

Publications and source records attributed to J J Wielenga.

6 recordsLinked to original sources
PubMed1992

Monoclonal antibodies specific for canine CD4 and CD8 define functional T-lymphocyte subsets and high-density expression of CD4 by canine neutrophils.

The characteristics of canine homologues of CD4 and CD8, defined by murine monoclonal antibodies CA13.1E4 (IgG1) and CA9.JD3 (IgG2a) respectively, are described. These antibodies identify mutually exclusive subpopulations of non-B lymphocytes in peripheral lymphoid organs and blood. However, in thymus the antibodies defined populations of double-positive, double-negative and single-positive cells that showed a progressive maturation consistent with that described for CD4 and CD8 in other mammalian species. Furthermore, functional studies clearly associated cytotoxic effector cell function with the subpopulation reactive with CA9.JD3 (CD8). In contrast, proliferation stimulated by allogeneic cells and mitogens was more pronounced in the subpopulation reactive with CA13.1E4 (CD4). Cell and tissue distribution studies revealed that CA13.1E4 stained neutrophils with equivalent intensity to the staining of peripheral T cells. CA13.1E4 precipitated a 60 kD protein from the surface of T cells and highly purified neutrophils under both reducing and nonreducing conditions. CA9.JD3 precipitated a heterodimer of 32 kd and 36 kD under reducing conditions, and a 70 kD protein under non-reducing conditions. The expression of CD4 by canine neutrophils is without precedent in other mammalian species; the functional significance of neutrophil CD4 expression is puzzling in light of the current understanding of the functions of CD4 which include it's role as a receptor for nonpolymorphic regions of MHC class II molecules.

Animals↗
PubMed1990

Highly increased production of bone marrow-derived blood cells by administration of homologous interleukin-3 to rhesus monkeys.

Recombinant rhesus monkey interleukin-3 (IL-3) was administered to normal rhesus monkeys in graded doses ranging from 3 to 30 micrograms/kg/d subcutaneously for 30 consecutive days or given as a continuous intravenous infusion at a dose of 30 micrograms/kg/d for 16 days. After a lag phase of about 1 week, a highly increased, dose-dependent production of bone marrow-derived blood cells was observed, preceded by amplification of bone marrow hematopoietic progenitor cells. Simultaneously, peripheral blood progenitor cells rose. The increase included basophilic, eosinophilic and neutrophilic granulocytes, monocytes, and the erythrocyte and platelet lineages. Characteristically, a T-lymphocyte response was absent. It is concluded that IL-3 in vivo stimulates blood cell production from an immature, multipotent progenitor cell.

Animals↗
PubMed1990

Interleukin-3.

Interleukin-3 (IL-3) is a hemopoietic growth factor involved in the survival, proliferation and differentiation of multipotent hemopoietic cells. In five mammalian species, including man, the gene encoding IL-3 has been isolated and expressed to yield the mature recombinant proteins. The human IL-3 gene encodes a protein of 133 amino acids with two conserved cysteine residues and 2 potential N-linked glycosylation sites; human native IL-3 has not been characterized. Comparison of the IL-3 genes revealed a more rapid evolutionary divergence than has been observed for other hemopoietic growth factors, and, hence, a more pronounced species specificity of the functional proteins was found. In agreement with its stimulatory action on immature multipotent cells, the in vivo actions of homologous recombinant IL-3 in nonhuman primates include a highly increased production of blood cells along the neutrophilic, eosinophilic and basophilic granulocyte as well as the monocyte, red cell and platelet lineages.

Animals↗
PubMed1990

Factors influencing reconstitution by bone marrow transplantation.

Reconstitution of levels of pheripheral blood cells following bone marrow transplantation is dependent on the engraftment of the pluripotent hemopoietic stem cells of the transplant. In the case of allogeneic transplants, a successful engraftment carries a high risk of the development of GvHD, which is a serious and often life-threatening complication. T cell depletion of the allogeneic bone marrow graft can completely prevent GvHD provided a sufficient degree of depletion is achieved. Experiments with laboratory animals and clinical experience have shown that the higher rate of graft failure that occurs with T cell depleted marrow grafts can be avoided by increasing the conditioning dose of TBI with approximately 2 Gy. Experiments with T cell depleted autologous bone marrow grafts and with grafts of autologous purified stem cells in monkeys demonstrate that the decreased engraftment of T cell depleted bone marrow cannot be ascribed to a trophic function of T lymphocytes, e.g. via production of hemopoietic growth factors. Using sublethally irradiated Rhesus monkeys, the effect of post-irradiation treatment with GM-CSF or with Rhesus monkey r IL-3 was studied. Enhancement of blood cell regeneration was only recorded within a relatively small TBI dose range. When the dose of TBI induces more than approximately a 3-log stem cell kill, treatment with growth factors becomes ineffective. Comparable results are obtained when supralethally irradiated monkeys given relatively small grafts of T cell depleted autologous bone marrow were treated with the hemopoietic growth factors.

Animals↗
PubMed1990

Phase II study of lomustine, cytarabine, mitoxantrone, and prednisone (CAMP) combination chemotherapy for doxorubicin-resistant intermediate- and high-grade malignant non-Hodgkin's lymphoma.

A phase II study was conducted to evaluate the efficacy and toxicity of lomustine, cytarabine, mitoxantrone and prednisone (CAMP) chemotherapy in doxorubicin-resistant intermediate- and high-grade malignant non-Hodgkin's lymphomas (NHL). Among 30 patients, the complete remission rate was 27% (duration: 10, 16, 22, 35, 35+, 42+, 51+, 55+ months) and the partial remission rate was 20%. Median survival for complete responders was more than 4 years. The best responses were seen in patients with relapsed NHL compared to those with primary refractory NHL. Toxicity was mainly related to myelosuppression. The results suggest that the CAMP schedule can be applied on an outpatient basis with satisfactory efficacy in patients with relapsing intermediate- and high-grade malignant NHL.

Antineoplastic Combined Chemotherapy Protocols↗