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Biomedical subjects

I A Cooper

Publications and source records attributed to I A Cooper.

68 records · Page 4Linked to original sources

Evidence for a new mechanism of cytotoxicity of 1-beta-D arabinofuranosylcytosine.

Inhibition of DNA synthesis by a pulse of 1-beta-D-arabinofuranosylcytosine (ara-C) results in reinitiation of DNA replication in DNA segments replicated earlier in that S phase and hence double replication of some DNA segments. Experiments were with tissue culture cell lines of human origin. DNA replicated early in S phase was labeled with a pulse of [3H]deoxycytidine with the cells pulsed later in S phase with ara-C. The DNA replicated after the time of the ara-C pulse was density labeled with 5-bromodeoxyuridine. Reinitiation of DNA replication in the already replicated [3H]DNA segments was demonstrated using CsCl density gradient analysis by an increase in the 3H label present in the light-heavy peak of semiconservatively replicated DNA. Also, in DNA of control cells, all of the 3H was in the same strand of the light-heavy DNA duplex as was the 5-bromodeoxyuridine, as shown by alkaline CsCl density gradient analysis of purified light-heavy DNA. However, after a pulse of ara-C, utilization of [3H]DNA strands as template strands was demonstrated by the presence of 3H label at the density of unsubstituted DNA chains in alkaline CsCl gradients of the purified light-heavy DNA. This double replication phenomenon can explain certain chromosomal abnormalities induced by ara-C.

Cell Cycle↗

Transfer RNA and transfer RNA methylase activity in spleens of patients with Hodgkin's disease and histiocytic lymphoma.

tRNA levels, base composition, and tRNA methylase activities of normal and tumor tissue from the spleens of 24 patients (18 with Hodgkin's disease and 6 with histiocytic lymphoma) were studied. There were no significant differences in major base composition of normal and tumor tissue. Methylated guanosine was increased in tumor tissue of some patients, and tRNA methylase activities were increased in extracts from the tumors.

Hodgkin Disease↗

Thymus with B lymphocytes in chronic lymphocytic leukaemia.

A 67-year-old man with a diagnosis of chronic lymphocytic leukaemia died suddenly following a coronary occlusion. Peripheral blood lymphocytes labelled with fluorescein conjugated polyvalent antisera to immunoglobulin and immunoglobulin G, and failed to label with absorbed antithymocyte serum. At necropsy, a large thymic tumour, and enlarged mediastinal lymph nodes also contained immunoglobulin G bearing B lymphocytes. The paradoxical finding of B lymphocytes with monoclonal surface immunoglobulin in a thymic mass is most unusual in chronic lymphocytic leukaemia.

Aged↗

Splenectomy for haematological cytopenias in patients with malignant lymphomas.

Haematological cytopenias caused by increased splenic activity occurred in 86 patients with malignant lymphomas (50 patients with stage III or IV Hodgkin disease [H.D.] and 36 with non-Hodgkin lymphomas). Splenectomy was performed in 84 of these 86 patients. There was complete or partial correction of the haematological defect in 90% of the H.D. patients and 89% of the non-Hodgkin patients. Chemotherapy or radiotherapy was started after the haematological defect had been corrected by splenectomy, and as a result 79% of the H.D. patients and 75% of the non-Hodgkin patients had a complete or partial remission of their disease. Increased splenic activity should be considered as a cause of a haematological cytopenia in patients with malignant lymphomas even in those with bone-marrow involvement, since splenectomy is accompanied by excellent results in terms of disease remission with subsequent therapy. 2 patients with H.D. (4%) and 5 with non-Hodgkin lymphomas (14%) died in hospital after splenectomy. Thus the operation was associated with acceptable mortality and morbidity despite the advanced stage of disease in most cases.

Anemia↗

Thymic origin of abnormal lymphoid cells in Sézary syndrome.

A patient with a 5-year history of pruritus and progressive and generalized erythroderma was found to have abnormal lymphocytes in the peripheral blood and mononuclear dermal infiltrate, all of which are features consistent with those described in Sézary syndrome. Systemic chemotherapy produced an almost complete resolution of skin lesions and pruritus. Serial studies on the abnormal cells included responses to phytohemagglutinin, cytogenetics, and immunofluorescence tests for identification of B or T lymphocytes. The abnormal cells demonstrated hyperdiploidy; the ratio of B to T cells fell whenever abnormal lymphocytes appeared in the peripheral blood, and returned to normal when abnormal cells disappeared from circulation. Lymphocytes separated from a skin nodule labeled as T cells. We conclude that the abnormal lymphocytes in this patient are of thymic origin.

Biopsy↗