PubMed Health⌕ Search

Biomedical subjects

D D Ma

Publications and source records attributed to D D Ma.

At least 55 records · Page 3Linked to original sources
PubMed1985

Decreased ecto-5'nucleotidase activity of peripheral blood lymphocytes in human monoclonal gammopathies: correlation with tumor cell kinetics.

Ecto-5'nucleotidase (5'NT) activity of peripheral blood (PB) lymphocytes was determined in 31 patients with serum monoclonal gammopathies (MG). Twenty-one patients had a diagnosis of multiple myeloma (MM), and ten patients had monoclonal gammopathy of undetermined significance (MGUS). The proliferative activity of the bone marrow plasma cells (LI%) was investigated in 28 of these MG patients by means of tritiated thymidine uptake evaluated by simultaneous autoradiography and cytoplasmic immunofluorescence. 5'NT activity was significantly lower in MG patients as compared with normal controls. MM patients had lower 5'NT activity than MGUS patients, but the difference was not significant. By contrast, MM had significantly higher LI% than MGUS patients. There was a linear regression of 5'NT on LI% which was statistically significant: the higher the LI%, the lower the 5'NT. Because the LI% is an accurate prognostic and monitoring factor in MG, this correlation indicates that 5'NT may be of assistance in predicting the clinical progress of MG patients. In seven MGs, the PB T and B lymphocytes were studied separately. The T cell subpopulation was 5'NT deficient compared to the normal controls, shown as a significant linear regression of T cell 5'NT on the LI%. This suggests that in MG there may be an alteration of nonneoplastic T lymphocytes correlated with tumor growth. The OKT8+ lymphocytes were mainly responsible for the 5'NT deficiency of unseparated T lymphocytes.

5'-Nucleotidase↗
PubMed1984

DNA strand breakage and ADP-ribosyl transferase mediated DNA ligation during stimulation of human bone marrow cells by granulocyte-macrophage colony stimulating activity.

ADP-ribosyl transferase (ADP-RT) is a chromatin-bound nuclear enzyme catalysing the transfer of ADP-ribose from NAD+ to chromatin proteins. The enzyme is activated by DNA strand breaks and has been suggested to have roles in both DNA repair (via its effect on DNA ligase II) and in differentiation. We recently demonstrated that specific inhibitors of ADP-RT preferentially inhibit differentiation of human granulocyte-macrophage progenitor cells to the macrophage lineage and that the specific proliferation/differentiation stimulus granulocyte-macrophage colony stimulating activity (GM-CSA) activates ADP-RT in human marrow cells within 3 h of exposure. The purpose of this study was to investigate the role of ADP-RT in monocyte-macrophage differentiation. By altering the time of addition of ADP-RT inhibitor it was demonstrated that maximal inhibition of macrophage differentiation only occurs when the inhibitor is added within the first 24 h of culture. This suggests that it is an early event during the induced differentiation of granulocyte-macrophage progenitor cells which requires ADP-RT. Fluorometric assay of the level of DNA strand breaks showed that GM-CSA induces DNA strand breaks which are rapidly ligated only if ADP-RT is available. These data and those of our earlier studies suggest that DNA rearrangement may be involved in differentiation of granulocyte-macrophage progenitors to the monocyte-macrophage pathway. Such a DNA rearrangement could provide a molecular basis for commitment of multipotent progenitors to a single lineage.

Bone Marrow↗
PubMed1984

Mitoxantrone in relapsed and refractory acute leukemia.

Mitoxantrone is a relatively new synthetic anthracenedione derivative with intercalating properties. An in vitro study with established leukemia cell lines indicated that DNA strand breaks were caused by mitoxantrone; when these were progressive after the initial insult, the cell line was sensitive to the drug. Clinical trials involved patients with relapsed and/or refractory acute leukemia. None of the patients receiving a single slow infusion of mitoxantrone achieved a complete remission. A five day treatment regimen produced an overall response rate of 48% with a complete remission rate of 25%. Toxicity in these preliminary studies was limited compared to that expected with the anthracycline antibiotics. Alopecia and nausea were the only commonly observed side effects. The trials were too short, however, to evaluate possible cardiac toxicity. Mitoxantrone is an acute and relatively nontoxic agent that merits further study to identify its role in the first line therapy of acute leukemia; such studies are underway.

Acute Disease↗
PubMed1984

Effect of thymosin on glucocorticoid receptor activity and glucocorticoid sensitivity of human thymocytes.

Incubation with thymosin fraction 5, (TMS F5 at 300 micrograms/ml) a partially purified thymic factor, reduced the steroid binding activity of human infant thymocytes from 9.6 +/- 2.1 fmole/ml to 5.0 +/- 2.0 fmole/ml. The glucocorticoid receptor activity in normal infant thymocytes was found to be 2,146 +/- 726 (s.d.) sites per cell with dissociation constant of 1.4 +/- 0.6 X 10(-8)M. TMS F5 also increased the resistance of human thymocytes to the cytolytic effect of dexamethasone (2.5 X 10(-8)M) to 168.6 +/- 30.2% of control (P less than 0.01). In animals, medullary and peripheral blood T cells are more resistant to glucocorticoids than immature thymic T cells. The results show that thymosin can induce changes consistent with differentiation in human thymocytes. These in vitro results are consistent with a physiological role of thymosin in intrathymic T cell maturation in man. Incubation of a human malignant thymus derived T cell line (MOLT 3) with TMS F5 also resulted in a significant reduction of the number of steroid binding sites to 44.2 +/- 15.3% of control (P less than 0.05), but TMS F5 did not significantly reduce the glucocorticoid sensitivity of MOLT 3 cells.

Cell Line↗
PubMed1983

Effect of thymosin and phorbol ester on purine metabolic enzymes and cell surface phenotype in a malignant T-cell line (MOLT-3).

Previous studies have shown that thymosin (fraction 5) is able to induce surface differentiation markers on normal murine bone marrow T-cell precursors. Phorbol ester (TPA) promotes differentiation of human leukaemic lymphoblasts as assessed by changes in phenotypic surface markers and terminal deoxynucleotidyl transferase (TdT) activity. Changes in levels of purine degradative enzymes occur during T-cell maturation with a fall in adenosine deaminase (ADA) and a rise in purine nucleoside phosphorylase (PNP) and 5'nucleotidase (5'NT) activities. We have now investigated the effect of both thymosin (fraction 5) and TPA on a human leukaemic T-cell line (MOLT-3) in expression of the surface antigenic markers NAI/34 (a marker of immature thymocytes) and OKT11 (which corresponds to the sheep erythrocyte receptor) and of TdT, ADA, PNP and 5'NT. Thymosin (after 96 h incubation) significantly reduced the number of cells positive for NAI/34 from 76.0 +/- 5.0% (mean +/- S.D.) to 51.3 +/- 9.3% (p less than 0.01) but caused no significant change in the percentage of TdT or OKT11 positive cells. ADA levels were significantly reduced (p less than 0.02) and 5'NT levels were significantly elevated (mean increase 303 +/- 142% of control, p less than 0.001) but the increase in PNP level (108 +/- 16.8% of control) was not significant (p greater than 0.05). On the other hand, TPA (after 96 h incubation) significantly reduced cells positive for NAI/34 from 76.0 +/- 5.0 to 30.0 +/- 9.8% and for TdT from 81.7 +/- 6.5 to 17.3 +/- 4.4% and increased OKT11 positive cells from 67.3 +/- 5.5 to 89.0 +/- 2.8% (p less than 0.001). TPA caused no significant change in 5'NT or ADA levels (p greater than 0.05), but an increase in PNP level to 158 +/- 12.9% of control (p less than 0.02). The present study demonstrates for the first time that the normal thymic hormone, thymosin is capable of inducing differentiation changes in thymic derived human leukaemic cells. In addition, it shows that different inducing agents may cause different patterns of differentiation changes in leukaemic cells.

5'-Nucleotidase↗
PubMed1983

Sequential studies on the role of mitoxantrone in the treatment of acute leukaemia.

Mitoxantrone, a synthetic and newly available intercalating agent, was shown to have activity in relapsed or refractory acute leukaemia, which is apparently schedule dependent. A 5-day treatment programme demonstrated impressive activity, with a 50% response rate and 24% complete remissions. Toxicity in these preliminary studies was limited compared to that expected with the anthracycline antibiotics. Mitoxantrone is an active and relatively non-toxic agent which merits further assessment prior to its incorporation in first-line therapy of acute leukaemia.

Acute Disease↗
PubMed1983

Comparison of purine degradative enzymes and terminal deoxynucleotidyl transferase in T cell leukaemias and in normal thymic and post-thymic T cells.

Adenosine deaminase (ADA), ecto 5' nucleotidase (5'NT), purine nucleoside phosphorylase (PNP) and terminal deoxynucleotidyl transferase (TdT) were measured in the cells of patients with acute or chronic T cell leukaemia and compared with normal putative prothymocytes (large, blast-like cortical thymocytes), cortical and medullary thymocytes and peripheral blood T lymphocytes. Distinct patterns of enzyme activities were found in the individual types of T cell leukaemia. Mean ADA, TdT and 5'NT activities in thymic acute lymphoblastic leukaemia (Thy-ALL) were 41.9 u/10(8) cells, 31.1 u/10(8) cells and 4.7 u/10(6) cells respectively; in chronic T cell leukaemia they were 7.1 u/10(8) cells, 0.6 u/10(8) cells and 18.1 u/10(6) cells respectively. Mean PNP activity was similar between these two groups of leukaemia (68.6 u/10(6)cells in Thy-ALL and 77.9 u/10(6) cells in chronic T cell leukaemia). The activities of these four enzymes in OKT4+ chronic T cell leukaemia did not differ significantly from those in the OKT8+ chronic T cell leukaemia cases. The activities of TdT, ADA, PNP and 5'NT in Thy-ALL closely resembled those in normal immature thymocytes, and in the chronic T cell leukaemias showed a similar pattern of enzyme activities to that of mature T lymphocytes. These findings are consistent with surface phenotypic studies of T cell malignancies which suggest that different T cell leukaemias represent malignant proliferation of T cell clones arrested at different stages of T cell differentiation. They also demonstrate the value of biochemical markers in defining the different subtypes of acute and chronic leukaemia.

5'-Nucleotidase↗
PubMed1983

Biochemical and immunological differentiation of human thymocytes induced by thymic hormones.

Changes in levels of purine degradative enzymes have been shown to occur during T-cell maturation in both rats and humans with a fall in adenosine deaminase (ADA) and a rise in purine nucleoside phosphorylase (PNP) and 5'-nucleotidase (5'NT) activities. We have investigated the effects of four thymic factors: thymosin fraction 5 (TMS-F5); thymosin alpha 1 (TMS-alpha 1); thymopoietin pentapeptide (TP-5); and thymic conditioned medium (CM) on TdT activity, purine enzyme levels and the phenotypic markers OKT3 (a marker for mature T cells) and NA1/34 (which reacts with immature cortical thymocytes) in human thymocytes and in the lymphoid leukaemic cell lines RPMI-8402 and JM1 (derived from Thy-ALL). All four thymic factors caused one or more maturation change in human thymocytes, e.g. TMS-F5 caused a significant increase in OKT3 expression, TMS-alpha 1 a fall in TdT and ADA activities and a rise in OKT3-positive cells, TP-5 an increase in PNP and CM a rise in 5'NT activity. TMS-F5 also caused a marked elevation of 5'NT in both the T lymphoblastic lines (P less than 0.001). On the other hand the non-physiological phorbol ester, 12-O-tetradecanoyl phorbol acetate (TPA), a tumour promotor with potency of inducing differentiation in some leukaemic cell lines, induced changes in both normal thymocytes and in the leukaemic line JM1 were inconsistent with maturation, e.g. a fall in the percentage of OKT3 cells. These observations suggest that maturation of normal thymocytes might proceed stepwise, each step requiring at least one of the thymic hormones. Although thymosin also induces differentiation changes in a malignant lymphoid line, the pattern of these differs from that induced in their normal counterparts.

Animals↗
PubMed1982

ABO-incompatible bone-marrow transplantation: removal of red blood cells from donor marrow avoiding recipient antibody depletion.

Eight patients with acute leukaemia undergoing allogeneic bone-marrow transplantation from ABO-incompatible donors received red-cell-depleted donor marrow without any procedure to diminish their anti-ABO antibody titres. Successful marrow red-cell removal (mean 98.8%) was achieved by means of a large-volume separation technique on Ficoll-Metrizoate in the IBM 2991 blood-cell processor. Clinically significant ABO-haemolytic reaction was prevented in all patients, and there was neither failure of engraftment nor rejection. This approach used alone is satisfactory for most ABO-incompatible marrow-transplant recipients, although combining this with some method of recipient antibody depletion, such as plasma exchange, is recommended in the occasional patient with high anti-ABO titres.

ABO Blood-Group System↗
PubMed1982

5'nucleotidase, adenosine deaminase and purine nucleoside phosphorylase activities in acute leukaemia.

Three enzymes concerned in purine degradation, 5'nucleotidase (5'NT), adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP) have been measured biochemically in the bone marrow or peripheral blood blasts from 75 patients with acute leukaemia, from 18 patients with blast crisis of chronic granulocytic leukaemia and in the bone marrow and peripheral blood lymphocytes from 14 normal donors. Characteristic patterns among the different sub-types of acute leukaemia have been detected, with high ADA, low 5'NT and PNP in Thy-ALL, high 5'NT and ADA in c-ALL, high PNP and low ADA in AML. The cells in CGL blast transformation resembled the enzymatic pattern of either AML or c-ALL respectively. However, no significant correlation was found between any pair of enzymes in any group of leukaemia, normal bone marrow or peripheral blood lymphocytes studied here.

Acute Disease↗
PubMed1982

Autopsy findings in bone marrow transplantation.

Autopsies were performed on 2 patients with aplastic anaemia and 7 with acute leukaemia dying after bone marrow transplantation. Neutropenic enterocolitis was found in 2 of the 3 early deaths occurring before marrow engraftment and was related to radiation or cytotoxic drug damage to the bowel mucosa in the presence of profound neutropenia, allowing infection by bowel organisms. Cytomegaloviral infection was universal in engrafted patients. One had cytomegaloviral (CMV) pneumonia, one CMV hepatitis and enteritis and one CMV enteritis. Three patients had occasional CMV inclusions in various organs without obvious harmful effects. One nonengrafted patient also had CMV pneumonia. Graft versus host disease (GVHD) was a significant finding in 4 engrafted patients. This was difficult to separate histologically from the effects of CMV in the bowel, but easier in liver and skin. The skin changes of GVHD were the most easily interpretable. Interstitial pneumonia was due to CMV in one nonengrafted and one engrafted patients and had no obvious infective cause in 2 engrafted patients. The presence of bizarre epithelial cells in the lungs of these patients suggested an aetiological role for radiation or cytotoxic drugs. Modification of the conditioning regimen may reduce tissue damage and lessen many of these side-effects.

Adult↗
PubMed1982

Distribution of terminal deoxynucleotidyl transferase and purine degradative and synthetic enzymes in subpopulations of human thymocytes.

Terminal deoxynucleotidyl transferase (TdT) and purine metabolic enzymes were examined in subsets of human infant thymocytes (defined by surface cell antigens) and normal peripheral T lymphocytes. Putative prothymocytes (RFB-1+, HTA-1+/- large blast-like cells), medium and high density cortical thymocytes (RFB-1+, HTA-1+), and medullary thymocytes (RFB-1-, HTA-1-, OKT3+) were isolated by density gradient centrifugation, monoclonal antibody and complement-mediated cytolysis, and cell-antibody affinity chromatography. Peripheral T lymphocytes were isolated from normal adult mononuclear cells using nylon fiber technique. Adenosine deaminase (ADA) and TdT were highest in prothymocytes 48.8 +/- 14.7 mumol/hr/10(8) cells (mean +/- SE) and 22.9 +/- 1.4 U/10(8) cells, respectively. Both enzymes decreased progressively down the maturation pathway. In peripheral T lymphocytes, ADA was 3.9 +/- 1.5 mumol/hr/10(8) cells, and TdT was undetectable. Purine nucleoside phosphorylase (PNP) and ecto-5'nucleotidase (5'NT) were lowest in cortical thymocytes (27.5 +/- 11.0 nmol/hr/10(6) cells and 2.8 +/- 1.3 nmol/hr/10(6) cells, respectively) and increased with T cell maturation. The PNP level was 124.9 +/- 17.2 nmol/hr/10(6) cells and 5'NT was 30.1 +/- 3.9 nmol/hr/10(6) cells in peripheral T lymphocytes. The deoxynucleoside kinases (deoxyguanosine, deoxyadenosine, and deoxycytidine kinases) paralleled the changes in ADA and TdT activity among the different T subsets. The proliferative activity (labeling index) was highest in the prothymocyte fraction and lowest in peripheral T cells. Variation in the distribution of these enzymes in T cell subsets may explain their different sensitivities to deoxyadenosine and deoxyguanosine toxicity and the different effects on T cell development of ADA or PNP deficiency.

Adenosine Deaminase↗
PubMed1982

Enzymes of purine metabolism in human peripheral lymphocyte subpopulations.

Ecto-5'nucleotidase (5'NT), adenosine deaminase (ADA), purine nucleoside phosphorylase (PNP) and deoxycytidine (CdR), deoxyguanosine (GdR), deoxyadenosine (AdR) and adenosine (AR) kinases have been measured in subpopulations of peripheral blood lymphocytes of eight healthy volunteers. The separation of B, T, T helper/inducer and T suppressor/cytotoxic cells was performed by means of density gradient centrifugation, E rosetting, passage through a nylon-wool column and antibody affinity chromatography utilising OKT8 and OKT4 monoclonal antibodies. ADA was significantly higher in T lymphocytes and 5'NT in B lymphocytes. Among T cell subpopulations, 5'NT activity was significantly higher (P less than 0 . 01) in T suppressor/cytotoxic (OKT8+) cells (32 . 9 units/10(6) cells than in T helper/inducer (OKT4+) cells (9 . 7 units/10(6) cells). Indeed, the 5'NT activity in T suppressor cells was similar to that in B cells. T helper cells tended, however, to have higher PNP and ADA activities than T suppressor cells but the differences were not statistically significant. No major differences were noted in kinase activities between any of the lymphocyte subpopulations.

5'-Nucleotidase↗
PubMed1980

Cytotoxic-induced fulminant hyperpyrexia.

Two cases of fulminant hyperpyrexia induced by cytotoxic agents (bleomycin in a patient with lymphoma, and daunorubicin in a patient with acute myeloblastic leukemia) are presented. Each patient had a fever greater than 42 degrees C, with a shock-like reaction and coma. Evidence of disseminated intravascular coagulopathy developed in the patient with bleomycin-induced hyperpyrexia and she died 24 hours afterwards. The pathogenesis and management of hyperpyrexial reactions to cytotoxic drugs are discussed.

Adult↗