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Biomedical subjects

I A Cooper

Publications and source records attributed to I A Cooper.

At least 55 records · Page 3Linked to original sources
PubMed1983

Requirements for growth of human erythroid progenitors in nutrient agar.

Human erythroid bursts and neutrophil colonies from fetal liver, term cord blood, and adult bone marrow were grown in nutrient agar, and the colonies were scored using a fixed whole plate method. Human placental conditioned medium was shown to contain burst promoting activity, and low oxygen tension markedly enhanced growth of erythroid bursts. Morphological analysis of colonies showed that eosinophil colonies were more numerous in bone marrow than fetal liver and conversely macrophage and neutrophil-macrophage colonies were more numerous in fetal liver. Erythroid bursts were more numerous and larger in fetal liver. Human fetal liver cells do not produce endogenous colony-stimulating factor.

Adult↗
PubMed1983

Blastic transformation of chronic lymphocytic leukemia.

A case is described of a patient with chronic lymphocytic leukemia whose disease underwent blastic transformation. The transformed cells had the same immunoglobulin types (mu and kappa) as the original chronic lymphocytic leukemia cells. Immunoperoxidase staining technique demonstrated that, in the transformed cells of the bone marrow, much of the immunoglobulin was intracellular. In the peripheral blood the transformed cells had dense surface immunoglobulin and features of primitive T-cells. These findings suggest that transformation to an immunoblastic type of leukemia had occurred.

Antigens, Neoplasm↗
PubMed1983

Aberrant replication of chromosomal DNA segments in CHO cells as a manifestation of a DNA repair system.

We have previously demonstrated that transient blocking of DNA synthesis with drugs such as 1-beta-D-arabinofuranosylcytosine results in some segments of the chromosomal DNA being replicated more than once in a single cell cycle. One explanation for this phenomenon might be that it is due to a perturbation of the cellular mechanism which normally controls the process of initiating replication of the chromosomal DNA and which ensures that each DNA segment is normally replicated once only in each cell cycle. To examine an alternative explanation, we have used the Chinese hamster ovary CHO-K1 cell line to test whether UV irradiation induces aberrant double replication of chromosomal DNA segments. We present data which show that UV irradiation induces a linear increase (regression coefficient, 0.996) in aberrant reinitiation of DNA replication in DNA segments replicated earlier in the same cell cycle. This was shown by DNA strands labelled with bromodeoxyuridine (BrdU) being synthesized off 3H-labelled template strands which were themselves synthesized during a [3H]thymidine pulse shortly before the UV irradiation. We suggest that blocked replication forks trigger an emergency response to unreplicated DNA segments in which abnormal origins of replication are used to circumvent this damage. This results in abnormal patterns of DNA replication, and it occurs whether DNA replication forks are blocked metabolically (such as with an inhibitor of DNA polymerase) or physically (as in the case of pyrimidine dimers).

Animals↗
PubMed1983

Mantel irradiation for stage I and stage II Hodgkin's disease--results of a 10 year experience.

One hundred and thirty patients with Stage I and II supradiaphragmatic Hodgkin's disease treated with mantle irradiation alone at the Peter MacCallum Hospital, Melbourne between 1968-1977 were analysed retrospectively. The median followup was 7.4 years with a minimum of three years. There were 64 clinically staged (CS) and 66 pathologically staged (PS) patients. The major difference between the two groups was the transdiaphragmatic relapse which occurred in 33% of CS patients, and 7.5% in PS patients. The actuarial five year relapse free survival (RFS) was 48% for CS patients and 67% for PS patients, but the five year overall survival was 90% for both groups, reflecting the impact of salvage treatment. Avid attention must be given to radiotherapy techniques to minimise local treatment failures. High grade nodular sclerosis Hodgkin's disease is associated with poor RFS even after adjustment has been made for stage and constitutional symptoms (p less than 0.003). Further studies will be made on this group of patients who may benefit from combined modality treatment. For PS I and II patients mantle irradiation gives a five year RFS of 67%, thus offering potential for cure in these patients.

Actuarial Analysis↗
PubMed1983

Adriamycin combinations as salvage therapy in advanced MOPP-resistant Hodgkin's disease.

Thirty one patients with advanced MOPP-resistant Hodgkin's disease were treated with adriamycin, bleomycin, vinca alkaloid and prednisolone (ABVP). Sixteen patients received vinblastine, seven received vincristine and in eight VM26 was substituted for the vinca. Of 28 patients evaluable for response 17 (61%) achieved an objective response with five (18%) complete responders. Response was significantly inferior in patients receiving VM26. Patients with a prolonged interval since previous chemotherapy had a greater chance of complete response (p less than 0.02) as did those with previous complete response to MOPP therapy (p less than 0.05). Response to treatment did not affect overall survival (p = 0.8) although relapse free survival was significantly longer for those achieving complete response (p less than 0.01). The regimen produced minimal gastrointestinal toxicity, but significant myelosuppression. ABVP is a well tolerated salvage therapy in advanced MOPP-resistant Hodgkin's disease.

Adolescent↗
PubMed1982

Characteristics of enzymatic DNA methylation in cultured cells of human and hamster origin, and the effect of DNA replication inhibition.

In mammalian cells, inhibitors of DNA replication have been shown to induce chromosomal aberrations, cell death and changes in gene control. Inhibition of DNA synthesis has been reported to induce hypermethylation of mammalian DNA (enzymatic postsynthetic formation of 5-methylcytosine). These 5-methylcytosines in mammalian DNA have variously been suggested to be important in gene control, DNA repair, and control of DNA replication. In establishing the normal characteristics of enzymatic DNA methylation, we have demonstrated that, in asynchronously growing cells of both human and hamster origin, some cytosine methylation is delayed for several hours after strand synthesis and that this delayed methylation is completed before the DNA strand acts as a template for DNA replication in the next S-phase. Further, in testing whether the deleterious effects on mammalian cells of DNA synthesis inhibitors might be mediated via changes in enzymatic DNA methylation, we have found, contrary to some previous findings, no evidence for any change in the level of DNA methylation in DNA strands synthesized during 6 h of treatment of cells of human origin with high concentrations of four different inhibitors of DNA replication or during the 4 h following the 6 h treatment. Almost totally blocking DNA replication had no effect on the small amount of delayed methylation of DNA strands not involved in semi-conservative replication during the time of the experiment. This lack of effect on DNA methylation was obtained when the labelling medium contained normal, undialysed serum. In contrast, if dialysed serum was used in the labelling medium in order to maximize L-[Me-3H]methionine utilization, highly variable, totally irreproducible patterns of apparent DNA hypermethylation were obtained.

5-Methylcytosine↗
PubMed1982

Pattern of isoaccepting transfer RNAs common to 26 patients with Hodgkin's disease.

The elution profiles of aminoacyl transfer RNAs from Hodgkin's tumors have been compared with the corresponding patterns from normal splenic tissue. Aminohexyl-Sepharose and reversed-phase 5 chromatography have been used in the fractionation studies. Three peaks of acceptor activity have been observed in phenylalanyl, histidyl, aspartyl, and asparaginyl transfer RNAs. A second peak was shown in the case of tyrosyl and methionyl transfer RNAs. Seryl transfer RNA showed no change in elution profile; namely, a single species was observed in both normal and tumor transfer RNAs. These observations are confirmation that Hodgkin's disease is a malignant disease. The uniformity of the extra species of tRNA suggests that there is a commonly occurring aberration in the cell of origin of the Hodgkin's tumor.

Chromatography↗
PubMed1982

Relationship between aberrant DNA replication and loss of cell viability in Chinese hamster ovary CHO-K1 cells.

We have previously presented evidence that a transient block to DNA replication induces an aberrant form of DNA synthesis. The most feasible explanation for this data is that the block to DNA replication results in some segments of the chromosomal DNA being replicated more than once in a single cell cycle. This form of aberrant DNA synthesis was demonstrated to occur following direct inhibition of DNA replication by 1-beta-D-arabinofuranosylcytosine or 9-beta-D-arabinofuranosyladenine or after indirect inhibition with cycloheximide. We have proposed mechanisms whereby this phenomenon could induce chromosome damage and cell death. In this paper, we present data on the relationship between this aberrant form of DNA replication and the loss of cell viability. Using Chinese hamster ovary CHO-K1 cells growing as monolayer cultures, we have simultaneously monitored the loss of cell viability as measured by colony formation and the relative extent of this aberrant DNA replication induced by 2-hr pulses of a series of concentrations of inhibitors of DNA replication. We have found that, with either direct inhibition of DNA replication with 1 beta-D-arabinofuranosylcytosine or with indirect inhibition, with cycloheximide, pulses of inhibitor administered to Chinese hamster ovary cells at increasing of this aberrant DNA replication which paralleled the increase in cell killing.

Animals↗
PubMed1981

Bone marrow necrosis diagnosed during life: clinical and laboratory features of extensive involvement.

Bone marrow necrosis occurred in two patients with non-Hodgkin's lymphoma. One had a four-year history of lymphoma for which he received combination chemotherapy. Severe bone pain, abdominal pain and fever occurred during the terminal part of his illness. The other patient presented initially with symptoms of bone pain and lymphadenopathy. At bone marrow examinations, both had anatomically extensive bone marrow necrosis with associated evidence of involvement by lymphoma. The previously recognized clinical features of bone marrow necrosis and its complications occurred in one or both of these illustrative cases, with the exception that bone tenderness was absent in both. Attempts were made to correlate the technetium-99m sulphur colloid scans with sites of disease as determined by the bone marrow examinations.

Aged↗
PubMed1981

Evidence for double replication of chromosomal DNA segments as a general consequence of DNA replication inhibition.

We have previously presented evidence that a transient inhibition of DNA synthesis by a pulse of 1-beta-D-arabinofuranosylcytosine (ara-C) results in a disruption of the pattern of replication of the chromosomal DNA of cultured human cells, resulting in some DNA segments being replicated more than once in a single S phase. Further evidence is presented in this paper that this effect is not a specific property of the ara-C molecule in that a similar effect is produced in cells by a pulse of 9-beta-D-arabinofuranosyladenine (ara-A) and also by a pulse of cycloheximide. The activated form of ara-A and ara-C (the triphosphates) both inhibit DNA synthesis at the level of the polymerase. Double replication following an ara-A pulse demonstrates that double replication after an ara-C pulse is not caused by some specific property of the ara-C molecule which might be unrelated to any effect on DNA synthesis. However, cycloheximide is an inhibitor of mammalian protein synthesis and inhibits DNA synthesis only indirectly, probably through a consequent deficiency of DNA-packaging proteins. Hence, the occurrence of double replication of chromosomal DNA segments following a pulse of cycloheximide is consistent with this phenomenon being a general and nonspecific consequence of the freezing of DNA replication forks.

Cell Line↗
PubMed1979

Plasmapheresis in the treatment of thrombotic thrombocytopenic purpura: a report of five cases.

Thrombotic thrombocytopenic purpura, an acute clinical disorder of uncertain aetiology, has previously been associated with almost 100% mortality. Dramatic response to exchange transfusion has been reported, and there is some evidence that a circulating immune complex may be involved in the pathogenesis. Therefore, it was decided to employ large-volume plasma exchange by means of a continuous-flow cell separator in the management of five patients with this disease. Three patients showed a dramatic response, which was manifested by rapid correction of the neurological deficit and of the abnormalities in laboratory findings. We conclude that the thrombotic thrombocytopenic syndrome should be regarded as an indication for emergency plasma exchange.

Adolescent↗
PubMed1979

Intensive leukapheresis in the management of cytopenias in patients with chronic lymphocytic leukaemia (CLL) and lymphocytic lymphoma.

The role of leukapheresis was explored in the management of anaemia and thrombocytopenia complicating the accumulation of lymphoid cells in patients with chronic lymphocytic leukaemia and lymphoma. The aim of this study was to determine the efficiency of this procedure in correcting these complicating features and to assess the length of response and the clinical well being of the patients. Twenty such patients with either chronic lymphocytic leukaemia or lymphocytic lymphoma were studied using a Continuous Flow Cell Separator (Aminco Celltrifuge). All had persistent significant anaemia and/or thrombocytopenia prior to the institution of leukapheresis. The procedure was carried out on alternate days until significant reduction in total circulating lymphoid cells had been achieved, an average of 2.9 x 10(11) cells being removed on each occasion. Thirteen of the twenty patients showed a significant elevation of both haemoglobin and platelet level concomitant with reduction in lymphoid cells. A reduction in organomegaly was also observed. These patients were classified as "responders," but the other patients failed to show correction of the haematologic parameters. This procedure permitted a number of responder patients to receive more specific treatment but in some it obviated the necessity for any further management for up to 12 months. Surface marker studies were also carried out on the lymphocytes of these patients. The patients who showed the best response to leukapheresis had cells characteristic of those seen in chronic lymphocytic leukaemia. The reduction of cells (82%) was greater in those who responded to this treatment than in the non-responder group (72%). The procedure was well tolerated by all patients and overall provided a long-term control of disease which outweighed the initial cost incurred.

Aged↗
PubMed1979

Hodgkin's disease terminating in acute leukaemia: report of seven cases.

Acute nonlymphocytic leukaemia developed in seven patients treated for Hodgkin's disease. All had received intensive radiotherapy and chemotherapy. One patient had clinical evidence of active Hodgkin's disease at the time of diagnosis of acute leukaemia, and of four other patients who had a post mortem examination another showed evidence of Hodgkin's disease. The median time from the first presentation with Hodgkin's disease to the development of acute leukaemia was 7.7 years. Chromosomal abnormalities were found in four patients. A preleukaemic phase was present in three patients. Survival following diagnosis of acute leukaemia was short (median four weeks) and only one patient achieved a complete remission. Although published data suggests that radiation exposure is an important aetiologic factor in the induction of acute leukaemia in patients with Hodgkin's disease, it appears likely that additional chemotherapy may have a significant potentiating effect.

Acute Disease↗
PubMed1979

The binding of ouabain to normal and chronic lymphocytic leukemic lymphocytes.

The binding of the cardiac glycoside, ouabain, to cells had been used to quantify the number of active cation pumps. In this study, lymphocytes were incubated with 3H-ouabain and the equilibrium binding analyzed for the maximal number of specific binding sites. Lymphocytes from normal peripheral blood bound 44,200 +/- 9920 molecules/cell, compared with 29,200 +/- 8370 molecules/cell for the lymphocytes of chronic lymphocytic leukemia (CLL) subjects. This difference was significant (p less than 0.01) and did not reflect a lower number of sites on B cells than T cells, since B-cell-enriched lymphocytes from normal peripheral blood showed the same ouabain binding characteristics as the standard T-cell-rich preparation. Although monocytes bind threefold more ouabain than lymphocytes, the small monocyte contamination (3.0%) in normal lymphocyte preparations could not account for the difference between normal and CLL. The fewer ouabain binding sites on CLL lymphocytes may reflect both their smaller size (by 10%) and lower mitotic activity compared with lymphocytes from normal peripheral blood.

B-Lymphocytes↗