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Biomedical subjects

R M Lowenthal

Publications and source records attributed to R M Lowenthal.

At least 73 records · Page 4Linked to original sources

Erythrocyte membrane proteins in an unusual case of congenital dyserythropoietic anaemia type II (CDA II).

Analysis of the erythrocyte membrane protein of an atypical case of congenital dyserythropoietic anaemia type II (CDA II) by electrophoresis on polyacrylamide gels revealed marked abnormalities. One-dimensional analysis showed a pronounced decrease in levels of B1.1 components, an increase in the level of B1.4 and the appearance of new components in the A region as well as in the C region of the gel. There were no artefacts due either to the presence of early red cells or to abnormally high levels of proteolytic enzyme activity in the CDA II preparations. Two-dimensional analysis confirmed the alterations in membrane components showing two novel A region species not reported in other studies of this disease. Abnormalities in components of such large molecular size may explain the greater degree of membrane perturbation seen in the present case and support the idea that CDA II may embrace more than one disease entity.

Adult↗

Immunological types of lymphoproliferative disorders in a cohort: a 4-year study.

Immunological testing of malignant cells and serum from most cases of lymphoproliferative disorders (LPD) allows the cell type to be characterised as of B, T or "null" lymphocyte origin. Regional differences in the incidence of neoplasms of these types have been reported. Furthermore, most published series have drawn cases from referral institutions rather than the general population. In order to determine the true incidence of a cohort we surveyed an entire population, that of Tasmania, an island state of Australia with a population of 410,000, during a defined period, the years 1977-1980 inclusive, for the occurrence of LPD. A total of 248 cases was discovered, made up of 133 cases of non-Hodgkin's lymphoma (NHL), 30 of chronic lymphocytic leukaemia (CLL), 18 of acute lymphoblastic leukaemia (ALL), 54 of multiple myeloma (MM), eight of macroglobulinaemia (MGA) and five others. We identified B lymphocytes by the presence of surface membrane immunoglobulin (Smlg) and their ability to rosette with mouse red blood cells, and T lymphocytes by their ability to rosette with sheep red blood cells. Laboratory testing was performed in 201 (81%) of the cases and characterisation of the cell of origin as of B, T or "null" type was successful in 158 (64%). Of these 158, 136 (86%) were B, 4 (3%) T, and 18 (11%) "null". On B cell subtyping by heavy and light chain lg analysis the Tasmanian series, compared with other reports, had an apparent paucity of B-CLL, MM and MGA of lambda subtype (57 k to 12 lambda, k:lambda ratio 4.8:1) and an unusual incidence of B-CLL with the double lg heavy chain combination M+G. Surveys of this type may help to point to environmental or other factors important in the aetiology of LPD.

Australia↗

2. Lymphocyte surface marker studies in lymphoma and leukemia.

In the past decade, studies of the markers expressed on the surface of malignant lymphocytes from patients with lymphoma and leukemia have greatly expanded our knowledge and understanding of these disorders. In addition, the results obtained have allowed individual cases to be categorized to prognostic groups, thus influencing the choice of therapy. These studies should now be considered routine in the evaluation of patients with lymphoid leukemias and lymphomas.

Antibodies, Monoclonal↗

Bone marrow transplantation using fractioned total body irradiation: Absence of pulmonary toxicity despite cytomegalovirus viraemia.

Bone marrow transplantation was performed on a 22-year-old male with acute myeloid leukaemia in early relapse. The donor was his HLA-identical, but ABO-incompatible, brother. Total body irradiation (TBI) was given in six daily doses of 2GY rather than as the usual single dose of 10GY. After transplantation, cytomegalovirus viraemia occurred, but the patient did not develop pneumonia despite the reported high association of these events. Four hundred days after transplantation, the patient was fit and active with no haematological abnormalities. The use of fractionated TBI may be associated with a lower incidence of respiratory complications than standard single-dose TBI.

Adult↗

Graft-versus-host disease in consecutive patients with acute myeloid leukaemia treated with blood cells from normal donors.

Two consecutive patients with acute myeloid leukaemia (AML) developed severe probable graft-versus-host disease (GVHD) following transfusion of blood products from normal donors. In one patient the AML had arisen de novo, while in the other it occurred four years after the patient developed non-Hodgkin's lymphoma (NHL) and was treated with radiotherapy and combination cytotoxic chemotherapy. Both patients received anti-leukaemic treatment with doxorubicin and cytosine arabinoside and intensive haematological supportive care with transfusions of red cell, white cell and platelet concentrates obtained from normal donors. Clinically the GVHD in each patient was manifest by a severe erythematous rash, intractable diarrhoea and abnormalities in the liver function tests. On pathological examination the skin in each case showed the typical changes of GVHD. Both patients died. There have been few previous reports of GVHD occurring after accidental engraftment of immunosuppressed patients undergoing therapy for acute leukaemia. Our experience suggests that it may occur more often than has hitherto been recognised. At present there is controversy concerning the possible anti-leukaemic effects of granulocyte transfusions. Until the relative importance of the benefits and deleterious effects of cells with the potential for engraftment is determined by further studies, we recommend the routine irradiation of all cellular blood products intended for administration to acute leukaemia patients undergoing intensive cytoreductive chemotherapy.

Cytarabine↗

A case of IgG lambda lymphoma occurring in a patient with previous IgG kappa lymphoma.

When a patient with non-Hodgkin's lymphoma (NHL) undergoes a relapse, immunological testing of malignant lymphocytes usually shows that the relapse cells are derived from the original tumor clone. We have observed a patient with a B cell lymphoma whose cells bore surface membrane IgG kappa at diagnosis and IgG lambda at clinical relapse 21 months later, during which time he had received multiple-drug chemotherapy. The shift from kappa to lambda light chain expression implies that the patient's apparent relapse was in fact due to the development of a second tumour. This may be another example of cytotoxic drug-induced carcinogenesis in a patient with a lymphoproliferative disorder.

Aged↗

Red blood cell requirements of human T lymphocyte colonies.

T lymphocytes were induced to form colonies by stimulating mononuclear cells with phytohaemagglutinin (PHA) prior to seeding in agar. The resultant colonies showed heterogeneity in the number of cells per colony and their location of growth, be it within the agar or, less frequently, on top of the agar. Colonies were subdivided according to their size and site of growth. The enhancing effect of sheep red blood cells (SRBC) was investigated through single and double agar experiments. The results indicated that SRBC and red blood cells (RBC) from other sources supported T lymphocyte colony development through a factor or factor(s) that diffused through the agar rather than by direct contact between RBC and the proliferating lymphocytes.

Animals↗

Congenital dyserythropoietic anaemia (CDA) with severe gout, rare Kell phenotype and erythrocyte, granulocyte and platelet membrane reduplication: a new variant of CDA type II.

A 43-year-old man with lifelong anaemia showed features which indicate him to have a previously undescribed variant of congenital dyserythropoietic anaemia (CDA), type II. The main clinical features--of which the first two are unique or very unusual in CDA--have been severe tophaceous gout, massive splenomegaly, gall stones mecessitating cholecystectomy and haemosiderosis affecting the liver and probably the heart. At age 41 he sustained a spontaneous retinal detachment. In the peripheral blood there were large numbers of nucleated red blood cells and marked macrocytosis; otherwise the picture was typical of CDA type II. The bone marrow contained many bi- and multi-nucleated erythrocyte precursors. There were increased levels of a number of red cell enzymes and a slightly raised level of HbF. Uncharacteristically, the red cells failed to lyse with acidified normal serum. The cells were strongly agglutinated by anti-i and were of the rare Kpb-negative phenotype. Plasma lipid analysis showed very low levels of cholesterol and vitamin E. Lipid peroxidation was markedly increased. Ultrastructural studies showed reduplication of the erythrocyte, granulocyte, and platelet cell membranes.

Adult↗

Ultrastructural studies of an unusual variant of congenital dyserythropoietic anaemia type II.

Electron microscopy of a new variant of congenital dyserythropoietic anaemia type II has yielded several unexpected results. The remarkable features include the relatively high percentage of erythrocytes with peripheral cisternae, the involvement of all bone marrow precursor cells, and the presence of ultrastructural defects in the granulocytes and platelets and on the cell surface of the erythrocytes. Experiments with vinblastine showed that this drug was capable of producing (in vitro) strikingly similar ultrastructural defects in healthy erythrocytes.

Anemia, Dyserythropoietic, Congenital↗

Collection, cryopreservation and subsequent viability of haemopoietic stem cells intended for treatment of chronic granulocytic leukaemia in blast-cell transformation.

We have stored at -196 degrees C peripheral blood buffy coat (BC) and bone marrow (BM) cells collected from 47 patients with chronic granulocytic leukaemia in the chronic phase. Dimethyl sulphoxide (DMSO) 10% was used as cryoprotective agent. As these cells include CFUc and probably pluripotential stem cells they may be transfused as part of the management of patients who enter blast cell transformation. The mean numbers of nucleated cells collected and stored per procedure was about 9 times greater for BC collections than for BM harvests (106 +/- 49 (SD) X 10(9) versus 11.9 +/- 6.6 X 10(9) respectively). Agar CFUc assay showed that stored cells may remain viable for up to 5 years. Since in vitro studies showed that CFUc proliferation is not inhibited by low concentrations of DMSO the removal of all DMSO during cell reconstitution before transfusion may not be necessary. If autologous BC cells are capable of repopulating the BM of patients treated for CGL in blast cell transformation the routine collection and storage of BC rather than BM cells may be desirable for all newly diagnosed patients.

Blood Preservation↗

Normal infant after treatment of acute myeloid leukaemia in pregnancy with daunorubicin.

Daunorubicin, thioguanine and cytosine arabinoside were administered from the 17th to 34th weeks of pregnancy in a 23-year-old patient with acute myeloid leukaemia. The patient went into remission of her leukaemia, and a normal male infant was born after labour was induced in the 40th week. This experience supports the view that modern regimens of anti-leukaemic drugs may be administered during the second and third trimesters of pregnancy without harmful effects on the foetus.

Adult↗

Plasma exchange in the long-term management of Waldenström's macroglobulinemia.

Two patients with Waldenström's macroglobulinemia (WM), which had become resistant to cytotoxic drugs, were treated for features of the hyperviscosity syndrome by repeated plasma exchange with the continuous-flow blood-cell separator over periods of 36 and 28 months, respectively. After four initial weekly plasma exchanges the procedure was carried out every 4 to 6 weeks and both patients tolerated it well. Relative viscosity of the serum was maintained within the normal range in one patient, and both patients remained free of symptoms of the hyperviscosity syndrome. The results suggest that treatment of WM by long-term "maintenance" plasma exchange alone should be considered in any patient with complications due to chemotherapy or whose disease fails to respond to chemotherapy.

Aged↗