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Biomedical subjects

J Wainscoat

Publications and source records attributed to J Wainscoat.

7 recordsLinked to original sources

Gene rearrangements in T-cell lymphoblastic lymphoma.

This study presents an examination of the Ig heavy chain (IgH) and T-cell receptor gamma (TCRgamma) genes in a series of 39 CD3-positive T-cell acute lymphoblastic leukaemia (ALL) cases with and without co-expression of CD79a; 30/39 cases had a rearrangement of the TCRgamma genes and two of these 30 cases also demonstrated an IgH rearrangement. No cases had solely an IgH rearrangement. The conclusion of the study is that lymphoblastic lymphoma cases that are positive for CD3 are of T-cell lineage, regardless of CD79a expression.

Adolescent↗

High fetal hemoglobin production in sickle cell anemia in the eastern province of Saudi Arabia is genetically determined.

Homozygous sickle cell disease in the eastern province of Saudi Arabia is clinically mild. Circulating fetal hemoglobin levels of 16.0 +/- 7.4% were found in these anemic patients, but only 1.09 +/- 0.97% in their sickle trait parents. To determine whether these sickle cell anemia patients inherit an increased capacity to synthesize fetal hemoglobin, a radioimmunoassay of fetal and adult hemoglobin was performed on erythroid progenitor (BFU-E)-derived erythroblasts from Saudi Arabian sickle cell patients and their parents. Mean fetal hemoglobin content per BFU-E-derived erythroblast from Saudi Arabian sickle cell patients was 6.2 +/- 2.4 pg/cell or 30.4 +/- 8.6% fetal hemoglobin (normal 1.1 +/- 0.7 pg/cell and 5.1 +/- 1.8%). Linear regression analysis of % HbF in peripheral blood versus % HbF per BFU-E-derived cell showed a positive correlation with an r of 0.65. The variance of the intrinsic capacity to produce HbF may account for almost 40% (r2) of the variance of circulating fetal hemoglobin but other factors, particularly selective survival of F cells, must also contribute significantly. Despite virtually normal HbF levels in sickle trait parents of these Saudi patients, mean fetal hemoglobin production per BFU-E-derived erythroblast in these individuals was elevated to 3.42 +/- 1.79 pg/cell or 16.1 +/- 6.4% fetal hemoglobin, and the magnitude of fetal hemoglobin production found in parents correlated with that of the patients. These data indicate that the high fetal hemoglobin in Saudi sickle cell disease is genetically determined but expressed only during accelerated erythropoiesis. Further evidence of such genetic determination was provided by analysis of DNA polymorphisms within the beta-globin gene cluster on chromosome 11. This revealed a distinctive 5' globin haplotype (+ + - + +) on at least one chromosome 11 in all high F SS and AS tested. The precise relationship of this haplotype to HbF production in this population remains to be defined.

Anemia, Sickle Cell↗

The expression of the Hodgkin's disease associated antigen Ki-1 in reactive and neoplastic lymphoid tissue: evidence that Reed-Sternberg cells and histiocytic malignancies are derived from activated lymphoid cells.

Ki-1 is a monoclonal antibody (raised against a Hodgkin's disease-derived cell line) that, in biopsy tissue affected by Hodgkin's disease, reacts selectively with Reed-Sternberg cells. The expression of Ki-1 antigen has been analyzed by immunocytochemical techniques in a wide range of human tissue and cell samples, including fetal tissue, malignant lymphomas (290 cases), and mitogen- and virus-transformed peripheral blood lymphocytes. The antigen was detectable on a variable proportion of cells in all cases of lymphomatoid papulosis and angio-immunoblastic lymphadenopathy and in 28% of the cases of peripheral T cell lymphomas (including lympho-epithelioid lymphomas). It was also expressed (more strongly) on tumor cells in 45 cases of diffuse large-cell lymphoma, most of which had originally been diagnosed as malignant histiocytosis or anaplastic carcinoma, because of their bizarre morphology. However, all of these cases lacked macrophage and epithelial antigens. Thirty-five cases expressed T cell-related antigens (associated in nine cases with the coexpression of B cell-related antigens), seven bore B cell-related antigens alone, and three were devoid of T and B cell markers. DNA hybridization with a JH specific probe showed a germline configuration in 11 cases of T cell phenotype, in two cases lacking T and B cell antigens, and in one case of mixed T/B phenotype, while rearrangement was found in two cases of clear B cell type and in one mixed T/B case. Expression of the Ki-1 antigen could be induced, together with interleukin 2 (IL 2) receptor, on normal lymphoid cells of both T and B cell type by exposure to phytohemagglutinin, human T leukemia viruses, Epstein-Barr virus, or Staphylococcus aureus. The results obtained indicate that Ki-1 antigen is an inducible lymphoid-associated molecule that identifies a group of hitherto poorly characterized normal and neoplastic large lymphoid cells. Tumors comprised solely of these cells show both morphological and immunological similarities to the neoplastic cells in Hodgkin's disease. This suggests that both disorders represent the neoplastic proliferation of activated lymphoid cells of either T cell or, less commonly, B cell origin. Disorders in which only a minority of cells express Ki-1 antigen (lymphomatoid papulosis, angio-immunoblastic lymphadenopathy, and certain T cell lymphomas) probably represent lesions in which only some of the abnormal cells have transformed into an "activation state." In direct support of this view is the finding that the Ki-1 expression in these lesions is accompanied by the expression of HLA-DR and IL 2 receptors.

Adolescent↗

Intravascular haemolysis after valve replacement: comparative study between Starr-Edwards (ball valve) and Björk-Shiley (disc valve) prosthesis.

Seventy-four patients with single prosthetic valves (Björk-Shiley or Starr-Edwards) in the mitral or aortic position and 18 controls with rheumatic valvar heart disease were investigated for evidence of intravascular haemolysis. Serum lactate dehydrogenase (LDH) was used as the most sensitive indicator of haemolysis. Raised concentrations were found in a third of 39 patients with Björk-Shiley prostheses (mean 281 IU/l) and in all 35 patients with Starr-Edwards prostheses (mean 859 IU/l. Values were considerably higher in patients with Starr-Edwards prostheses and particularly in those with aortic prostheses (mean 927 IU/l). Eight out of 12 patients with haemosiderinuria had Starr-Edwards valves. Intravascular haemolysis was of little clinical significance in patients with Björk-Shiley prostheses, but some patients with Starr-Edwards prostheses became iron deficient as a result.

Aortic Valve↗

Recurrent acquired sideroblastic anemia in a twin pregnancy.

A woman whose sideroblastic anemia had relapsed with progestogen and combined oral contraceptive therapy suffered further relapses in a (twin) pregnancy. Previous reports exist of relapses both from progestogens and in pregnancy, and we postulate a shared etiology. Affected women considering pregnancy or sex hormone usage should be advised accordingly.

Adult↗