Biomedical subjects

E N Metz

Publications and source records attributed to E N Metz.

At least 37 records · Page 2Linked to original sources

PubMed1979

Superiority of adriamycin-containing combination chemotherapy in the treatment of diffuse lymphoma: a Southwest Oncology Group study.

As a part of an ongoing prospective controlled trial, the Southwest Oncology Group compared the results of treatment of advanced non-Hodgkin's lymphoma with two CHOP regimens (cyclophosphamide, adriamycin, vincristine and prednisone with either low-dose bleomycin or BCG by scarification) to a COP regimen (cyclophosphamide, vincristine and prednisone) with low-dose bleomycin (COP-Bleo). The study design emphasized histopathology review and systematic restaging to define complete remission (CR). Confirmed rates of CR for 443 evaluable patients were 59% for 286 patients receiving the CHOP regimens and 59% for 157 patients receiving COP-Bleo. Rates of CR were higher for patients with nodular lymphoma (69%) compared to those with diffuse lymphoma (54%) (p = 0.005). For patients with nodular lymphoma there was no difference in CR rates according to treatment. For patients with diffuse lymphomas the CR rate was higher with the CHOP programs (58%) than with COP-Bleo (44%) (p = 0.10). Overall duration of CR and survival was significantly longer for patients with nodular lymphoma compared to diffuse lymphoma (p less than 0.01). At this time, remission duration and survival were similar regardless of induction regimen used in patients with nodular lymphoma. However, in patients with diffuse lymphoma, the duration of CR and overall survival were improved by treatment with the CHOP regimens compared to COP-Bleo (p = 0.02). Thus, in this controlled study we have demonstrated that initial combination chemotherapy employing the CHOP regimen was a superior remission induction therapy for patients with diffuse lymphoma.

Antineoplastic Agents↗

PubMed1978

Skin test conversion following transfer factor. A double-blinded study of normal individuals.

The use of skin test conversion as a measure of change in cellular immune status is a fairly routine procedure despite considerable potential for variation in testing. This study is a double-blinded and randomized reassessment of this assay in the context of transfer factor (TF) activity. Thirty-three normal people with negative tuberculin skin tests received either dialyzable TF, column purified TF, hypoxanthine, or saline in a randomized and double-blinded fashion. Skin test reactivity to tuberculin and keyhole limpet hemocyanin (KLH) was read by three of the investigators. Nine of 20 recipients of TF and 7 of 13 controls demonstrated an increase in tuberculin reactivity after "transfer." Four reactions were greater than 10 mm. Fourteen of 20 recipients of TF and 7 of 13 controls demonstrated some reactivity to KLH on initial testing post-transfer. Control solutions were as effective as TF preparations in "causing" skin test conversion. These observations stress the importance of controlled and and blinded studies when serial skin test reactivity is used to evaluate cellular immune status in humans.

Clinical Trials as Topic↗

PubMed1978

Adriamycin and daunomycin generate reactive oxygen compounds in erythrocytes.

Adriamycin and daunomycin produce dose-related cardiac toxicity that may be related to oxygen radicals. Addition of these compounds to human erythrocyte suspensions resulted in stimulation of hexose monophosphate shunt activity that was markedly impaired in the absence of oxyhemoglobin. Evidence for generation of hydrogen peroxide by these compounds was provided by oxidation of reduced glutathione, by 14C-formate oxidation, and by the catalase-aminotriazole trapping technique. These experiments indicate that Adriamycin and daunomycin interact with oxyhemoglobin to generate reactive oxygen metabolites. A similar interaction with oxymyoglobin may occur in the heart and produce oxygen radicals that injure cardiac myocytes.

Daunorubicin↗

PubMed1977

The effect of sodium azide on the chemiluminescence of granulocytes--evidence for the generation of multiple oxygen radicals.

It has been established that granulocytes generate superoxide (O-2) as well as hydrogen peroxide (H2O2) during phagocytosis. The chemiluminescence (CL) generated by phagocytes appears dependent on these oxygen radicals (or). however, recent studies suggest that oxygen molecules, including singlet oxygen (1O2) or hydroxyl radicals (OH-), may also be generated during phagocytosis and contribute to CL. We have tested this possibility by studying human granulocyte CL in the presence of 0.1 mM sodium azide, a known inhibitor of myeloperoxidase and catalase and a scavenger of 1O2. The effects of azide on CL were correlated with the effects of this compound on hexose monophosphate shunt (hmps) activity, nitroblue tetrazolium (NBT) dye reduction, formate oxidation, and cytochrome c reduction. CL generated by granulocytes during the phagocytosis of zymosan particles was markedly impaired by azide (24% to 47% of control values). On the other hand, phenomena dependent in part on the presence of O2 radicals, i.e., reduction of NBT dye and cytochrome c, were not impaired by the presence of azide. As would be expected, inhibition of catalase by azide virtually abolished the oxidation of formate, but the burst in HMPS activity associated with phagocytosis was augmented further. The latter observation indicated that azide did not impair generation of H2O2 but increased the relative amount detoxified via the HMPS. The experiment provides evidence that radicals other than O-2 and H2O2 are generated during phagocytosis and that these radicals are major contributors to the CL phenomenon.

Azides↗

PubMed1977

Effect of phagocytosis on the reduced soluble sulfhydryl content of human granulocytes.

The role of reduced glutathione in relation to hexose monophosphate shunt activity and peroxide detoxification has been well established in human erythrocytes. Less is known about the content of reduced glutathione in phagocytic leukocytes and the changes that occur during functional activity. We have measured the reduced sulfhydryl content of normal resting human granulocytes and of cells isolated from a patient with chronic granulomatous disease. Normal cells and those from the patient with chronic granulomatous disease contained similar concentrations of reduced sulfhydryls. Stimulation of a phagocytic response by incubation with opsonized zymosan particles resulted in prompt and nearly complete depletion of intracellular glutathione from normal granulocytes. This fall in reduced glutathione concentration was dependent on the phagocytic load. Exposure of chronic granulomatous disease granulocytes to a similar phagocytic load resulted in a slower and less complete fall in reduced glutathione. In normal cells, those from the chronic granulomatous disease patient, and those from an obligate carrier of the disease, the decrement in reduced glutathione during phagocytosis was correlated with oxidation of 14C-1-glucose and 14C-formate, nitroblue tetrazolium reduction, and the chemiluminescence phenomenon.

Glucose↗

PubMed1976

A comparison of the metabolic response to phagocytosis in human granulocytes and monocytes.

Recent studies indicate that oxygen radicals such as superoxide or singlet oxygen may be important in the functional activity of human granulocytes. We have examined the possible importance of these radicals in the functional capacity of human blood monocytes. Monocytes, like granulocytes, generate chemiluminescence during phagocytosis. Chemiluminescence is impaired 50-90% by superoxide dismutase, an enzyme which enhances the dismutation of superoxide to hydrogen peroxide. These results indicate that superoxide is related to the chemiluminescence generated by monocytes. Superoxide dismutase in a concentration which impaired chemiluminescence also impaired the staphylococcal killing by monocytes. Hexose monophosphate shunt activity and hydrogen peroxide production by granulocytes and monocytes were also evaluated. The oxidation of [1-14C]glucose was used as a measure of hexose monophosphate shunt activity and the oxidation of [14C]formate as an estimation of hydrogen peroxide production. The oxidation of both substrates by monocytes was increased during phagocytosis but, in contrast to results in granulocytes, was not further increased by the addition of superoxide dismutase. These data indicate that superoxide may be important in bactericidal activity of human monocytes. Our results also suggest that the metabolism of oxygen radicals in monocytes and granulocytes may be different.

Glucose↗

PubMed1976

Mechanisms of methylene blue stimulation of the hexose monophosphate shunt in erythrocytes.

The response of the hexose monophosphate shunt in erythrocytes was studied with the ionization chamber-electrometer apparatus to measure continuously 14CO2 derived from 14C-labeled substrates. The effect of methylene blue at high (0.1 mM) and low (1 muM) concentrations was evaluated under different gas mixtures; air, carbon monoxide, and 6% carbon monoxide in air. The latter gas mixture results in nearly 100% carboxyhemoglobin but provides a physiologic partial pressure of oxygen. The extent to which pentose is recycled through the shunt in response to methylene blue stimulation was examined with radioactive glucose substrates labeled on the first, second, and third carbon positions. Generation of hydrogen peroxide after stimulation of erythrocytes with methylene blue was evaluated by the catalase-aminotriazole trapping technique, [14C]formate oxidation, and oxidation of reduced glutatione. Stimulation of the shunt with 1 muM methylene blue was markedly impaired in the absence of oxyhemoglobin, but stimulation with 0.1 mM methylene blue was only slightly impaired under the carbon monoxide-air mixture. The higher concentration of methylene blue produced evidence of hydrogen peroxide generation of all three techniques. Despite the evidence for the involvement of oxygen, oxyhemoglobin, and hydrogen peroxide in the response to methylene blue, cells containing methemoglobin induced by sodium nitrite or from a patient with congenital methemoglobinemia responded normally to methylene blue in the absence of oxygen. These experiments indicate that the reactions induced by methylene blue in erythrocytes are more complex than generally thought and that high concentrations are associated with production of peroxide.

Carbon Dioxide↗

PubMed1975

Leukemic reticuloendotheliosis. A study of the origin of the malignant cell.

A highly pure preparation of neoplastic cells from the spleen of a patient with leukemic reticuloendotheliosis was studied for function, membrane characteristics and glucose metabolism. Glass adherence and phagocytosis of small particles (latex and carbon black) were demonstrated with phase contrast microscopy. Staphylocidal activity was similar to that of normal monocytes. Immunofluorescent assays revealed nonspecific uptake of antiserums to immunoglobulins G (IgG), M (IgM), A (IgA) and kappa and kappa and lambda light chains. Rosette assays indicated the presence of receptors for IgG on the surface of all cells but no receptors for complement (C3) or sheep red blood cells. Glucose metabolic studies revealed a pattern that differed from that of normal monocytes or lymphocytes with intermediate values for glycolysis, low hexose monophosphate shunt activity and high Krebs cycle activity. Increments in tritiated (3H)-thymidine uptake and glucose metabolism in response to phytohemagglutinin stimulation were minimal (5 per cent of normal lymphocyte values) and no response was noted with pokeweed mitogen stimulation. These findings suggest that the leukemic reticuloendotheliosis cell most closely resembles cells of the monocyte-histiocyte series.

Cell Separation↗

PubMed1975

Howell-Jolly bodies. A clue to splenic infarction.

A 74-year-old woman with secondary erythrocytosis was found to have Howell-Jolly bodies in peripheral blood erythrocytes following acute splenic infarction. The Howell-Jolly bodies were a transitory finding and disappeared six days after the infarction, although the spleen remained abnormal by isotope scanning for several weeks. Careful inspection of the peripheral blood film may be an aid in the diagnosis of acute splenic infarction.

Aged↗

PubMed1975

The response of red cell hexose monophosphate shunt after sulfhydryl inhibition.

In this investigation, we studied the importance of cellular glutathione (GSH) in the hexose monophosphate shunt (HMPS) activity of unstimulated human erythrocytes and the mechanism by which pyruvate stimulates the HMPS. The rate of HMPS activity was measured by the production of radioactive CO2 from 14C-1-glucose or 14C-1-ribose using a vibrating reed electrometer and ionization chamber. HMPS activity was not significantly impaired by N-ethylmaleimide (NEM) in concentrations which bound all red cell GSH. Red cells incubated under carbon monoxide (CO), an experimental condition which eliminates peroxide production, still had HMPS activity which was 44% of the value under air. Pyruvate stimulation of the HMPS was unaffected by doses of NEM which bound all cellular GSH or by incubation under CO. These data indicated that pyruvate stimulation of the HMPS occurs by pathways which do not involve peroxide formation, GSH, or oxygen. This study indicates that sulfhydryl blockade of GSH does not necessarily inhibit HMPS activity and that HMPS activity in red cells may respond to reactions not linked directly to glutathione reduction.

Blood Glucose↗

PubMed1974