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Biomedical subjects

M E Beard

Publications and source records attributed to M E Beard.

At least 73 records · Page 4Linked to original sources

Does multisomy of chromosome 1q confer a proliferative advantage in B-cell acute lymphoblastic leukemia?

Two patients fulfilled the clinical and hematologic criteria for B-cell acute lymphoblastic leukemia: the malignant cells had L3 morphology, bore B-cell markers, and carried the specific t(8;14) translocation. The leukemic cells of one patient were tetrasomic for 1q, and those of the other patient showed several separate cell lines with complete or partial trisomy of 1q. In the latter patient it appeared that a break close to the heterochromatin of 1q produced an unstable chromosome end which formed associations with the telomeres of at least seven other chromosomes. It is suggested that multisomy of 1q gives tumor cells a proliferative advantage and is secondary to the basic neoplastic event.

Adolescent↗

Host origin of in vitro bone marrow fibroblasts after marrow transplantation in man.

Two female patients who received bone marrow transplants from male donors showed the donor karyotype in all blood cells cultured with phytohemagglutinin and in all cells of bone marrow aspirate after direct or 24-hour culture preparation for cytogenetic study. The donor origin of myeloid cells was demonstrated specifically by identifying the male karyotype in the dividing cells of granulocyte/macrophage colonies in soft agar. Only the host female karyotype was found in fibroblast cell populations from cultured bone marrow aspirate. Bone marrow aspirate from transplant patients contained cells of host origin and cells of donor origin; both will proliferate in culture.

Anemia, Aplastic↗

The effect of donor pretreatment on interstitial dendritic cell content and rat cardiac allograft survival.

Different pretreatment schedules were applied to rat heart donors and their effect on heart interstitial dendritic cell content was observed using monoclonal antibodies and immunofluorescence techniques. Interstitial dendritic cell (IDC) numbers were correlated with the histology and survival of hearts transplanted into untreated allogeneic recipients. Hearts from AS donors pretreated with cyclophosphamide and total-body irradiation showed prolonged survival in DA recipients only when more than 95% of the graft interstitial dendritic cells were depleted. Reconstitution studies established that prolonged graft survival following donor pretreatment depended on the removal of bone-marrow-derived cells and that these were IDCs. These results suggest that the IDC is the most significant "passenger leucocyte", and that very small numbers of residual IDCs were still sufficient to cause rapid rejection. DA rat heart contained three times as many IDCs as the AS strain and DA hearts were much more difficult to deplete of IDCs. Pretreated DA hearts were rejected by AS recipients, although grafts with a lower IDC content resulted in an attenuated histological rejection response and a markedly decreased recipient lymphocytotoxin response. To be effective, donor pretreatment schedules had to be initiated 5 days prior to transplantation. Pretreatment 6 hr prior to transplantation failed to deplete IDC or prolong graft survival even in he weak (ASxDA)F1 to DA model. Pretreatment protocols used clinically have probably not removed IDCs adequately and the development of methods that deplete IDCs effectively could improve graft survival at no risk to the recipient.

Animals↗

Enrichment of pluripotent hemopoietic progenitor cells from human bone marrow.

Pluripotent hemopoietic progenitor cells (CFU-GEMM, cells forming mixed hemopoietic colonies in methylcellulose) from human bone marrow were enriched 90-fold by positive selection on the fluorescence-activated cell sorter using monoclonal antibody RFB-1. Bone marrow cells were separated by cell size, using log 90 degrees light scatter, and the cell fraction containing CFU-GEMM was further separated by relative fluorescence intensity for the RFB-1 antigen. Further enrichment, up to 150-fold, was achieved by depleting bone marrow of T cells and mature myeloid cells prior to RFB-1 selection. These procedures yield a cell fraction containing 51% blast cells, 2% promyelocytes, and 47% undifferentiated (lymphocyte-like) mononuclear cells, although only 1% of the cells formed a mixed colony. CFU-GEMM are strongly positive for the RFB-1 antigen, whereas morphologically identifiable erythroblasts, myeloblasts, and promyelocytes are weakly RFB-1+. This suggests that the relative concentration of the RFB-1 antigen on bone marrow cells is inversely related to their maturity. The greatly increased recovery of CFU-GEMM after the separation of bone marrow by log 90 degrees light scatter and the removal of T cells and mature myeloid cells suggested that accessory cells that normally regulate the cloning efficiency of CFU-GEMM were removed.

Adult↗

Nonrandom cytogenetic changes in New Zealand patients with acute myeloid leukemia.

Bone marrow clones with abnormal chromosomes were observed in 56% of 66 patients with forms of acute myeloid leukemia [French-American-British (FAB) M1-M6]. Acute myeloblastic leukemia (AML, M1 and M2) was the most common form, and 65% of these patients showed chromosomal abnormalities compared with 41% of patients with acute myelomonocytic leukemia (AMMoL, M4). The recognized nonrandom chromosomal abnormalities found were trisomy 8, monosomy 5 or 7, trisomy 1q, t(6;9), t(8;21), t(15;17), and abnormalities in 17q. There was also a strong involvement of chromosome No. 11: Abnormalities were found in eight patients when their leukemia was diagnosed and in a further three patients during the course of karyotypic evolution. Six of these patients had AMMoL or AMoL. Complex or multiple clones were found in 37% of AML patients at diagnosis. Our AML patients had a reduced frequency of abnormalities in chromosome No. 5 or 7 and an increased frequency of abnormalities in chromosome No. 8 compared with studies reported in other countries (p = 0.01). This difference suggests that in New Zealand AML might be caused by factors different from those operating in more industrialized centers.

Bone Marrow↗

Cytogenetic studies of acute promyelocytic leukemia.

Translocation t(15;17) is reported in bone marrow cells from six of seven patients with active acute promyelocytic leukemia (APL). One patient who showed t(15;17) at final relapse did not show it in directly prepared or cultured cells taken from a previous relapse. Bone marrow samples from two patients showed only cells with a normal karyotype in the direct preparation, whereas more than 60% of cells cultured for 24 hr showed t(15;17). R-Banding, G-banding, and an attempt at high-resolution banding indicated the break points t(15;17)(q24;21) for one of our patients.

Adult↗

Haemostasis in heat stroke.

A patient with moderately severe heat stroke was studied with particular attention to changes in haemostasis. Activation of fibrinolysis, a probable failure of hepatic synthesis of coagulation factors and severe thrombocytopenia were observed, but there was no definite evidence for disseminated intravascular coagulation (DIC). It is suggested, however, that in heat stroke of greater severity the more extensive tissue breakdown may lead to DIC. If DIC is superimposed on the above changes in haemostasis it is likely to be both sudden and overwhelming.

Adult↗

Bone marrow transplantation for acute leukaemia and severe marrow aplasia: an analysis of five patients.

Five patients, three with severe aplasia and two with acute leukaemia have been treated by bone marrow transplantation (BMT). Four are alive and well with excellent graft function. One showed engraftment but died of acute graft-versus-host disease (GVH); this patient and his donor were hepatitis B antigen positive. Three show evidence of mild chronic GVH, two patients requiring control by immunosuppressive therapy. Bone marrow transplantation (BMT) has now become an established method of treatment in severe aplasia and in acute leukaemia and our results serve to emphasise this. The clinical and organisational problems associated with BMT are discussed.

Adolescent↗

Right atrial catheters for long-term venous access.

Thirty-two Hickman central venous catheters were placed in patients suffering mainly from blood disorders. The catheters remained in situ for an average of 64 days. In 20 patients the catheters were removed either because they were no longer needed (14) or at death (6). In five patients they are still in position. Complications in seven patients led to the catheter being removed and these included four patients with catheter related sepsis. The use of these catheters allows safe long-term access to the venous circulation even in the neutropenic, immunosuppressed patient.

Bacterial Infections↗

Acute promyelocytic leukemia: cytogenetics and bone-marrow culture.

Six patients were diagnosed as having acute promyelocytic leukemia (APL) according to FAB criteria. One patient conformed to the M3 variant. Informative cytogenetic results (G-banding) on five of the patients showed that three of them, including the M3 variant, had the 15;17 translocation in bone-marrow or blood cells. Cells with the translocation were accompanied by cells with a normal karyotype in all patients and no other chromosomal abnormality was present. This first report of the 15;17 translocation from the South Pacific region is relevant to the uneven geographical distribution of APL patients with the translocation. Five of the six patients including the M3 variant, showed a distinctive pattern of cell growth in agar culture characterized by a profusion of small, uniform clusters containing 6-20 cells with the appearance of promyelocytes. The remaining patient had a pattern of cell growth more typical of M2 acute leukemia. This cell growth pattern may be useful in diagnosing and monitoring the course of APL.

Aged↗

The wound fibroblast and macrophage. II: Their origin studied in a human after bone marrow transplantation.

The origin of the wound fibroblast and macrophage was studied in a patient following bone marrow transplantation, using sex chromosome markers. Fibroblast-like cells emigrating from explants of a 5-day-old skin wound had the host karyotype, whereas macrophages had donor markers. These results suggest that the wound fibroblast in man is of local tissue origin, whereas wound macrophages are derived from haemopoietic tissue.

Bone Marrow Transplantation↗

A complex Ph1 translocation in a patient with primary thrombocythaemia.

Routine blood examination of a 27-year-old female revealed a platelet count of 2000 X 10(9)/l. Bone marrow cells showed the Philadelphia chromosome which was one product of a complex rearrangement of chromosomes 9, 22 and X. Her platelet count was lowered by plateletphoresis and chemotherapy. She remains in good health 19 months later, but her thrombocythaemia is considered to be an early manifestation of chronic myeloid leukaemia.

Adult↗