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Biomedical subjects

W E Fibbe

Publications and source records attributed to W E Fibbe.

156 records · Page 9Linked to original sources

Cytomegalovirus immunity and T lymphocytes in bone marrow donors and acute graft-versus-host disease.

T lymphocyte subset numbers in bone marrow grafts were correlated with the cytomegalovirus (CMV) antibody status of the donors and with the occurrence of acute graft-versus-host disease (GVHD) in their recipients. We studied whether or not the (previously reported) association between donor CMV antibodies and GVHD could be explained by CMV-related changes in T cell subsets in the marrow grafts. There were no significant correlations between any of the T cell subsets in the marrow grafts and the occurrence of grades II-IV GVHD. A particular subset of CD8+ T cells carrying the HNK1 marker was significantly increased in the marrow grafts of CMV-seropositive donors. Although recipients of marrow from CMV-seropositive donors received an average of five times more CD8+ HNK1+ T cells than those with CMV-seronegative donors, that situation was not associated significantly with the development of GVHD.

Acute Disease↗

Expression of CD11, CDw15, and transferrin receptor antigens on human hematopoietic progenitor cells.

The expression of transferrin receptor-associated antigens and of CD11 and CDw15 antigens was investigated on myeloid committed progenitor cells (CFU-GM day 10, CFU-GM day 7, and cluster-forming cells [CFC] day 4), on erythroid committed progenitor cells (BFU-E and CFU-E), and on multilineage progenitor cells (CFU-GEMM). Both complement-dependent cytotoxicity and fluorescence-activated cell-sorting assays were performed. Complement-dependent cytotoxicity appeared to be the more sensitive assay. Transferrin receptor-associated antigens appeared to be clearly present on all myeloid and erythroid committed progenitor cells, but were found to be only weakly expressed on CFU-GEMM. CD11 antigens appeared to be strongly expressed only on mature granulocytes, monocytes, and certain lymphocytes, but not significantly on myeloid committed precursor cells. Surprisingly, CD11 antigens were weakly, but significantly, present on CFU-E. CDw15 antigens appeared to be restricted to myeloid differentiation and were increasingly expressed from CFU-GM day 10 to CFC day 4. Thus, antitransferrin receptor, CD11, and CDw15 antibodies can be used to separate hematopoietic progenitor cells and may be useful tools in the study of hematopoietic differentiation.

Antibodies, Monoclonal↗

Interleukin-1 (22-K factor) induces release of granulocyte-macrophage colony-stimulating activity from human mononuclear phagocytes.

An electrophoretically pure preparation of natural human interleukin-1 (IL-1) was shown to stimulate in vitro colony formation in human bone marrow cultures. Day 4 myeloid cluster-forming cells (CFC), as well as early (day 7) and late (day 10) granulocyte-macrophage colony-forming units (CFU-GM) were stimulated in a dose-dependent fashion. At optimal concentrations of IL-1, the number of day 4 CFC reached 72%, the number of day 7 CFU-GM reached 32%, and the number of day 10 CFU-GM reached 80% of the respective numbers of colonies obtained by addition of crude leukocyte-conditioned medium (LCM). The IL-1-induced stimulatory effect on CFU-GM growth could be completely neutralized by a rabbit anti-IL-1 antiserum. Colony growth was abrogated by depleting the marrow cell suspensions of phagocytic cells prior to IL-1 addition. Conversely, the effect could be reintroduced by addition of marrow-derived adherent cells to bone marrow cell suspensions that had been depleted of both phagocytic and E rosetting T cells. Furthermore, media conditioned by bone marrow-derived adherent cells or by peripheral blood mononuclear phagocytes in the presence but not in the absence of IL-1, stimulated in vitro colony growth of phagocyte-depleted bone marrow cell suspensions. These results indicate that IL-1 induces release of granulocyte-macrophage colony-stimulating activity (GM-CSA) from human mononuclear phagocytes.

Bone Marrow↗

Human hematopoietic progenitor cells in long-term cultures express HLA-DR antigens and lack HLA-DQ antigens.

The expression of HLA-DR antigenic determinants on human hematopoietic progenitor cells (HPC) capable of differentiating into mature blood cells, as determined in semisolid cultures, has been demonstrated previously (3-7). Here, we investigated the expression of class II determinants on HPC responsible for the sustained proliferation of colony-forming units of granulocyte/macrophage (CFU-GM), of multilineage HPC (CFU-GEMM, granulocyte/erythrocyte/macrophage/megakaryocyte), and burst-forming units of erythroid cells (BFU-E) in liquid long-term cultures. Using both fluorescence-activated cell sorting and complement-dependent cytotoxicity assays, HLA-DR determinants could be identified on virtually all these HPC capable of proliferating in long-term cultures. Experiments in which the stromal layer had been irradiated provided evidence that the HPC themselves were truly HLA-DR+, and that the sustained proliferation of HPC was not due to activation of HLA-DR- residual HPC in the stromal layer by reinoculated HLA-DR+ accessory cells. Furthermore, it was shown that all HPC recognized in semisolid and liquid long-term cultures were HLA-DQ-. These results suggest that the human true pluripotential stem cell is HLA-DR+. These results open the possibility of studying class II-dependent regulation of hematopoiesis in liquid long-term cultures.

Cell Division↗

Intermediate and high-dose ARA-C and m-AMSA (or daunorubicin) as remission and consolidation treatment for patients with relapsed acute leukaemia and lymphoblastic non-Hodgkin lymphoma.

27 patients (aged 15-55 years) with relapsed acute myelogenous (AML) and lymphoblastic leukaemia (ALL), and with lymphoblastic non Hodgkin's lymphoma (NHL) have been treated with intermediate dose cytosine arabinoside (AraC, 1 g/m2 q 12 h X 12) and 3 d of m-AMSA (20 patients), 90-115 mg/m2 daily, or daunorubicin (7 patients). 18 of them attained a complete remission (AML 10/14, ALL 3/5, NHL 5/8). 7 patients received consolidation treatment with 1-2 courses comprising 4 d of AraC (3 g/m2 q 12 h X 8) and m-AMSA (90-115 mg/m2) on d 5 of each course. 2 patients underwent allogeneic bone marrow transplantation and 9 received no further treatment after remission induction. In addition to vomiting, fever and conjunctivitis, toxicity in 6 patients included a combination of severe diarrhoea, fever and signs of paralytic ileus. 3 of them died during the pancytopenic phase. The pancytopenic period ranged from 16-25 d (median 21 d) after the remission induction and 14-21 d (median 19 d) after the consolidation course. Median remission duration was 5 months for those patients who received no treatment after remission induction and greater than 9 months (4+ - 16+ months) for the patients who received consolidation courses. Increased dosages of AraC are active in relapsed leukaemia and lymphoma, although optimal dose and schedule are still undetermined.

Adolescent↗

Human erythroid progenitor cells express Rhesus antigens.

The expression of Rhesus antigens on hematopoietic progenitor cells was studied using monoclonal antibodies. Because these antibodies are not capable of lysing mature red blood cells in a complement-dependent cytotoxicity assay, fluorescence-activated cell sorting was performed. Using the monoclonal anti-Rh 29 antibody B10, 68% +/- 6% of the mature erythroid progenitor cells (CFU-E) were sorted into the positive fraction, while only 2% +/- 1% of the relatively immature erythroid progenitor cells (BFU-E), and 3% +/- 1% of the granulocyte-macrophage progenitor cells (CFU-GM) were cultured from this same fraction. Thus up to a 15-fold enrichment of CFU-E could be obtained. In two experiments more than 4% of the cells in the positive fraction consisted of CFU-E; in one experiment even more than 7% did. Using fractionated cell sorting, the Rhesus antigens appeared to have a lower density on CFU-E than HLA-DR determinants. Antibodies against the Rhesus antigens can be applied to enrich erythroid-committed stem cells and to separate mature from immature erythroid progenitor cells.

Antibodies, Monoclonal↗

Prognostic factors in IgD myeloma: a study of 21 cases.

A series of 21 patients with IgD myeloma was studied retrospectively, to assess which parameter present at the time of diagnosis was of prognostic importance for survival and whether the clinical staging system of Durie and Salmon had predictive value for the survival time of these patients. Survival time did not appear to be correlated with haemoglobin concentration, thrombocytopenia, initial level of M-protein, amount of Bence-Jones proteinuria, hypercalcaemia, serum creatinine level, presence of osteolytic lesions or hepatosplenomegaly. Neither did the staging system of Durie and Salmon predict the survival time. It is concluded that clinical staging is of limited value in the management and prediction of the survival time of IgD myeloma patients.

Adult↗

Experience with intermediate and high dose cytosine arabinoside in refractory acute leukaemia.

28 consecutive patients (age 15-58 years) with refractory acute leukaemia (24 AML, 4 ALL) have been treated with high or intermediate dose cytosine arabinoside (AraC). Twenty patients received AraC at a dose of 3000 mg/m2, twice daily for 6 days (13 patients AraC alone, 7 patients AraC and doxorubicin) and 8 patients received AraC at a dose of 1000 mg/m2, twice daily for 6 days and daunorubicin. 10 of the 20 patients treated with high dose AraC achieved a complete remission (50%) and 2 a partial remission. No patients in the intermediate dose AraC group achieved a remission (p = 0.05). Toxicity of these protocols was acceptable. Vomiting, headache, somnolence, fever, conjunctivitis, and minor cardiac arrhythmias were found most frequently. The pancytopenic period ranged from 16-30 days for the high dose protocol and 14-23 days for the intermediate dose protocol. Sophisticated isolation and blood banking facilities are required in this period. Median duration of remission was 6 months. Results obtained are in favour of the high dose protocol in refractory leukaemia. Only a large dosage increment of AraC can overcome refractoriness of leukaemic blast cells.

Adult↗

Bone marrow transplantation or chemotherapy as post-remission treatment of adult acute myelogenous leukemia.

We compared three consolidation regimens in patients with acute myelogenous leukemia in first remission. Thirty-four patients received only intensive consolidation chemotherapy (SIC); 28 patients were scheduled to undergo an autologous bone marrow transplant (auto-BMT) and 44 patients an allogeneic BMT (allo-BMT). Twenty-seven of them were referred in first remission for allo-BMT. Nineteen patients achieved a complete remission after salvage treatment. All other patients obtained a remission after one or two courses of a standard combination of cytosine arabinoside and daunorubicin. Except for the patients who were referred in remission, all patients received intermediate dose cytosine arabinoside and amsacrine as a first consolidation treatment. The median ages of the three groups were 48 (SIC), 39 (auto-BMT) and 33 years (allo-BMT). Two patients relapsed before auto-BMT and 1 before allo-BMT. The median interval from the date of complete remission to the auto- or allo-BMT was 3 months. In total, 80% of the patients of the SIC group relapsed, compared to 50% of the patients belonging to the auto-BMT group and 35% of the 44 patients who were scheduled to receive an allo-BMT. The overall median disease-free survival was 14 months, 30% of the patients being alive and disease-free at 3 years. The disease-free survival rate at three years was 25% for the SIC group, 30% for the allo-BMT group and 40% for the ABMT group (P = 0.45). Our study shows no benefit for bone marrow transplantation over intensive consolidation treatment. However, large randomized trials are required to define the real value of these treatment modalities.

Adolescent↗