bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nodular mixed lymphoma: results of a randomized trial failing to confirm prolonged disease-free survival with COPP chemotherapy
Authors: Glick JH , Barnes JM , Ezdinli EZ , Berard CW , Orlow EL , Bennett JM 
Published: October 2019

Abstract
Fifty-two patients with stage III or IV nodular mixed lymphocytic- histiocytic lymphoma (NM) were entered on a prospective randomized trial comparing cyclophosphamide-prednisone (CP) to either COPP (cyclophosphamide, vincristine, procarbazine, prednisone) or BCVP (BCNU, cyclophosphamide, vincristine, prednisone). The COPP regimen utilized in this Eastern Cooperative Oncology Group (ECOG) trial was similar to the four-drug regimen C-MOPP reported by the National Cancer Institute to achieve prolonged relapse-free survival in this histology. No significant differences in complete response rates, response duration, or overall survival were noted among the three regimens. A pattern of continuous late relapse was observed for all three chemotherapy programs. Although 11 of the 18 (61%) COPP patients achieved a complete response, only 3/11 (27%) remain disease-free with a median follow-up of over 3 yr. However, two of these three long-term complete responders have died with no clinical evidence of recurrent disease. The COPP patients received 84% of the calculated ideal doses of cyclophosphamide and 78% of the ideal dosage of procarbazine. Grade 3–4 hematologic toxicity was noted in 22% of the COPP group, 36% with BCVP, and 0% for the CP patients. We were unable to confirm the ability of COPP to achieve durable complete remissions in NM lymphoma. The cyclophosphamide-prednisone combination was equally effective when compared with COPP and BCVP, but produced minimal toxicity.
Prognostic relevance of thymidine kinase isozymes in adult non- Hodgkin's lymphoma
Authors: Ellims PH , Eng Gan T , Medley G , Van Der Weyden MB 
Published: October 2019

Abstract
To determine whether kinase (TK) isozyme status adds clinically useful information in adult non-Hodgkin's lymphoma (NHL), we have analyzed peripheral blood plasma and lymphocytes of 44 patients with NHL for either TK1 or TK2 isozyme activity. On the basis of isozyme status, patients could be divided into two groups that did not differ significantly with respect to known determinants for survival. The median survival of patients exhibiting peripheral blood TK1 thymidine kinase activity was 40 wk and that of individuals with TK2 activity was in excess of 200 wk. These data suggest that peripheral blood TK1 isozyme is a useful independent biochemical marker for a subgroup of NHL who respond poorly to current therapy and thus require new therapeutic approaches.
Autosomal Dominant familial erythrocytosis due to autonomous erythropoietin production
Authors: Distelhorst CW , Wagner DS , Goldwasser E , Adamson JW 
Published: October 2019

Abstract
A family is described in which four members spanning three consecutive generations have erythrocytosis associated with a normal hemoglobin oxygen affinity. When bone marrow from one affected family member was cultured in vitro, erythroid colonies formed only when erythropoietin was added to the culture. Serum erythropoietin, measured by radioimmunoassay, was significantly elevated above normal in each of the affected family members. Bioassayable erythropoietin was detected in the urine of two of the three affected family members. In two of the affected family members, erythropoietin was measured in serum by radioimmunoassay and in urine by bioassay before and for 4 days following an isovolemic phlebotomy, which reduced the red cell mass by 20%. Neither serum nor urinary erythropoietin levels changes following phlebotomy. The erythrocytosis in this family appears to be secondary to inappropriately increased erythropoietin production unassociated with a decrease in the blood oxygen-carrying capacity. This is the first instance in which autonomous erythropoietin production appears to be inherited on an autosomal dominant basis.
Serum erythropoietin (EST) titers in anemia
Authors: de Klerk G , Rosengarten PC , Vet RJ , Goudsmit R 
Published: October 2019

Abstract
Erythropoietin (ESF) titers were determined in sera from patients with different types of anemia using the fetal mouse liver cell bioassay. An inverse relationship was found between hemoglobin concentration and ESF titer. However, ESF titers differed markedly between patients at comparable degrees of anemia. Several groups of patients were distinguished on the basis of the activity of their erythroid bone marrow. In each of these groups, a significant negative correlation was found between the hemoglobin concentration and the logarithm of the ESF titer. ESF titers in patients with pure red cell aplasia were fourfold higher than those in patients with iron-deficiency anemia and tenfold higher than those in patients with megaloblastic anemia and homozygous sickle cell anemia at comparable hemoglobin concentrations. Following the initiation of specific therapy in patients with pernicious anemia and patients wit iron-deficiency anemia, serum ESF titers were found to decrease prior to any substantial rise in hemoglobin concentrations. In the patients with pernicious anemia, the lowest ESF levels were found 1 day after administration of vitamin B12, whereas in the patients with iron-deficiency anemia, the lowest ESF levels were reached in the second week of oral iron therapy. ON the basis of these data it was concluded that serum ESF titers in anemic patients are not only inversely related to the hemoglobin concentration but also to the activity of the erythroid bone marrow.
Utilization of monoclonal antibodies in the treatment of leukemia and lymphoma
Authors: Ritz J , Schlossman SF 
Published: October 2019

Abstract
The generation of murine monoclonal antibodies reactive with human leukemia and lymphoma cells has recently led to clinical trials that have begun to evaluate the use of these reagents in the treatment of various leukemias and lymphomas. Several of these studies have demonstrated that infusion of monoclonal antibody can cause the rapid and specific clearance of leukemic cells from the peripheral blood. Intravenously administered antibody also rapidly binds to bone marrow lymphoblasts, and in one instance, has resulted in the partial regression of tumor cell infiltrates in lymph nodes and skin. Unfortunately, clinically significant responses have not in general been achieved, but these clinical studies have identified specific factors that result in the development of resistance to antibody-mediated lysis in vivo. These factors include the presence of circulating antigen, antigenic modulation, reactivity of monoclonal antibody with normal cells, immune response to murine antibody, and the inefficiency of natural immune effector mechanisms. Current research is now being directed towards developing methods to circumvent each of these obstacles. Future clinical studies utilizing antibodies in vitro or with different specificity may demonstrate greater therapeutic efficacy. In addition, monoclonal antibodies can be used as carriers of other cytotoxic agents and in conjunction with other agents that will reduce the total load. Monoclonal antibodies represent new and powerful reagents that may in the near future become an additional therapeutic modality for patients with malignant disease.
Factor(s) responsible for the increase in alkaline phosphatase activity of postmitotic granulocytes from normal individuals and patients with chronic myeloid leukemia
Authors: Sato N , Mori M , Oshimura M , Ueyama Y , Miwa T , Ohsawa N , Kosaka K , Asano S 
Published: October 2019

Abstract
Using postmitotic granulocytes (PMGs) with low neutrophil alkaline phosphatase activity (NAP activity), factor(s) having the capacity to increase their NAP activity were examined in vitro. A high activity of the factor was demonstrated in the cystic fluid of a human squamous cell carcinoma, which is known to produce a large amount of granulocyte- macrophage colony-stimulating factor (GM-CSF). The NAP-stimulating factor increased NAP values both in PMGs from normal bone marrow and PMGs from patients with chronic myeloid leukemia (CML), and NAP values in cells treated with the factor approached or rose above those of normal peripheral granulocytes after 48 hr of culture. The effect of the factor was specific in that the factor caused stimulation only in granulocytic series. These findings may indicate that increases in NAP activity reflect maturation or granulocytes and that low NAP activity of neutrophils derived from patients with CML is due to the immaturity of these cells. The relationship between the factor responsible for the increase in NAP activity and GM-CSF is also discussed.
Translocation 4; 11 in acute lymphoblastic leukemia: clinical characteristics and prognostic significance
Authors: Arthur DC , Bloomfield CD , Lindquist LL , Nesbit ME Jr 
Published: October 2019

Abstract
Banded bone marrow chromosome analyses have been done on 83 unselected patients with acute lymphoblastic leukemia (ALL). Seven patients, all with non-T, non-B ALL, had a translocation involving the long arms of chromosomes 4 and 11. Five of these patients, 4 children and 1 adult, were first studied at diagnosis, and the t(4;11) (q21;q23) was the only karyotypic abnormality. All 5 presented with a marked leukocytosis (greater than 150 X 10(9)/liter). Four of these 5 patients achieved a complete remission following the same intensive treatment regimen; however, remission duration and survival were very short (medians 2.5 and 8 mo, respectively). The fifth patient is currently receiving induction chemotherapy. The remaining 2 patients, both adults, were studied in relapse only, and had other karyotypic abnormalities in addition to the t(4;11). One of these relapse patients was a female whose clinical presentation and course were similar to those above. The last patient was a male who presented with a leukocyte count of 7 X 10(9)/liter and maintained an initial complete remission for 37 mo. Our data suggest that patients who have a t(4;11) (q21;q23) at the time of diagnosis of ALL have a poor prognosis with conventional therapy and require a new therapeutic approach.
Abnormal deoxyuridine suppression test in congenital methylmalonic aciduria-homocystinuria without megaloblastic anemia: divergent biochemical and morphological bone marrow manifestations of disordered cobalamin metabolism in man
Authors: Carmel R , Goodman SI 
Published: October 2019

Abstract
We studied two brothers (J.R. and M.R.) with the cobalamin D variant of congenital methylmalonic aciduria-homocystinuria, whose previously reported lack of megaloblastic anemia conflicted with current concepts of cobalamin's role in DNA synthesis and the “methyltetrahydrofolate (MTHF) trap” hypothesis. Both subjects were indeed hematologically normal, although J.R. had a mean corpuscular volume of 96 fl. However, both demonstrated abnormalities in the deoxyuridine suppression test. J.R. had an abnormal suppression value of 21.0% (normal less than 10%) that was correctable by adding hydroxocobalamin or folic acid in vitro but not MTHF. M.R. had normal suppression (8.9%), but demonstrated worsening (18.6%) when MTHF was added. J.R.'s classical deoxyuridine suppression pattern of cobalamin deficiency thus supports the trap hypothesis. However, his lack of comparable morphological changes suggests that impaired de novo thymidylate synthesis and the trap hypothesis, though valid, may not fully account for the megaloblastic maturation accompanying cobalamin deficiency. Equally noteworthy was the deleterious effect of MTHF on M.R.'s marrow, suggesting its potential usefulness as an in vitro “stress test” for latent cobalamin abnormality.
Monoclonal antibodies that detect differentiation surface antigens on human myelomonocytic cells
Authors: Perussia B , Trinchieri G , Lebman D , Jankiewicz J , Lange B , Rovera G 
Published: October 2019

Abstract
We describe here the production and characterization of several new monoclonal antibodies that recognize differentiation antigens present on human cells of the myelomonocytic lineage. The lineage and the stage specificities of our reagents (myeloid-, monocytic-, and myelomonocytic- specific) were determined on the basis of their reactivity with human cell lines and with human peripheral blood and bone marrow cells. Cross- competition experiments demonstrated that some of the antibodies react with the same or closely associated antigenic determinants. Five antigens have been identified in this way: one present on myeloid, one on monocytic, and three on both myeloid and monocytic cells. The possible relationship of our antibodies with other established monoclonal antibodies is discussed, in addition to their use in the in vitro study of the differentiation pathways of human hemopoietic cells and in the characterization of leukemias.
Differential role of fractionated heparin in antithrombin-III proteolysis
Authors: Marciniak E 
Published: October 2019

Abstract
Commercial heparin was fractionated by affinity chromatography on immobilized antithrombin-III (AT-III) into nonbinding (NB), lower affinity (LA), and high affinity (HA) heparin, with specific anticoagulant activity of 9, 205, and 284 U/mg, respectively, Each fraction, in microgram quantities, was examined in the reaction of alpha-thrombin with a molar excess of 125I-labeled AT-III. Proteolysis of residual AT-III was assessed on the basis of distribution of radioactivity in SDS-polyacrylamide gels after electrophoresis. In the presence of HA heparin, 36% of AT-III participating in the reaction was degraded into a 50,000-dalton inactive fragment. Similarly designed proteolysis obtained in the presence of LA heparin was 21%, while in the presence of the NB fraction, or in the absence of heparin, only 8% of inhibitor was in the fragment form. When added to human plasma together with purified thrombin, both HA and LA heparin caused functional and electrophoretic changes suggestive of AT-III proteolysis. These observations support the concept that the conformational change, induced by binding of heparin, exposes specific polypeptide bonds susceptible to thrombin, except that nonproductive proteolysis may then occur even more rapidly than the formation of a stable enzyme-inhibitor complex. This, in turn, suggests that the presence of highly active heparin may contribute to reduction of the protective inhibitor in blood, if induction of proteolysis by thrombin is in effect.
New and rapid functional assay for C1 inhibitor in human plasma
Authors: Schapira M , Silver LD , Scott CF , Colman RW 
Published: October 2019

Abstract
C1 inhibitor (C1-INH) and alpha 2-macroglobulin (alpha 2M) account for over 90% of the inactivation of purified plasma kallikrein by normal human plasma. The rate of kallikrein inactivation is also dependent on the presence of high molecular weight kininogen (HMWK), which forms a reversible complex with kallikrein protecting the active site of the enzyme against inhibitors. By selectively inactivating alpha 2M with methylamine, and eliminating the protective effect of HMWK by dilution, the inactivation of kallikrein by plasma became almost exclusively dependent on C1-INH. Functional C1 inhibitor was assessed by measuring the pseudo-first-order rate constant for the inactivation of kallikrein by diluted methylamine-treated plasma in 29 individuals, including 11 controls, 11 oral contraceptive users, 5 patients with classical hereditary angioedema (HAE), and 2 patients with variant HAE. Over a wide range of concentrations, an excellent correlation (r = 0.90) was observed between functional and antigenic C1-INH among controls, oral contraceptive users, and patients with classical HAE. This new functional assay for C1-INH can be performed in less than 3 hr with commercially available reagents. Therefore, this assay will be helpful for the diagnosis and management of conditions associated with the deficiency of C1-INH, such as HAE.
The gamma-delta-beta-globin gene region in G gamma-beta +-hereditary persistence of fetal hemoglobin
Authors: Balsley JF , Rappaport E , Schwartz E , Surrey S 
Published: October 2019

Abstract
We report restriction endonuclease analysis of the gamma-delta-beta- globin gene region in a mother and child heterozygous for G gamma-beta +-hereditary persistence of fetal hemoglobin (HPFH). The affected chromosome in these persons directs the production of G gamma-chains and beta-chains but not A gamma-chains. DNA was digested with several restriction enzymes and was examined for gamma, delta, beta sequences by blot hybridization. Only normal digestion fragments were present. By sensitive methods, we were unable to detect a deletion in the entire gamma-delta-beta-globin gene region of the affected chromosome, indicating that in this family, G gamma-beta +-HPFH is not due to a large deletion.
5-Methyltetrahydrofolate related enzymes and DNA polymerase alpha activities in bone marrow cells from patients with vitamin B12 deficient megaloblastic anemia
Authors: Kano Y , Sakamoto S , Hida K , Suda K , Takaku F 
Published: October 2019

Abstract
The activities of 5-methyltetrahydrofolate (5-CH3THF) related enzymes and DNA polymerase alpha were determined in bone marrow cells obtained from patients with vitamin B12 deficient megaloblastic anemia and compared with those from healthy volunteers and patients with hemolytic anemia. 5-CH3THF homocysteine methyltransferase activity was significantly lower than that in the control subjects. 5,10- methylenetetrahydrofolate reductase activity was only slightly elevated to that in the control subjects. DNA polymerase alpha activity was significantly higher than that in the control. High deoxyuridine suppression test values in vitamin B12 deficient bone marrow cells were improved by tetrahydrofolate, but not by 5-CH3THF. These data indicate that, even though the reverse reaction catalyzed by 5,10- methylenetetrahydrofolate reductase may be operative in vitamin B12 deficiency, it is not sufficient to correct the disturbance in folate metabolism in vitamin B12 deficiency. Increased DNA polymerase alpha activity may be due to compensation for disarranged DNA synthesis.
Immunologic stimulation of early murine hematopoiesis and its abrogation by cyclosporin A
Authors: Burstein SA , Erb SK , Adamson JW , Harker LA 
Published: October 2019

Abstract
Mice injected chronically with antiplatelet serum develop an increase in the number of megakaryocytic progenitor cells compared to animals given normal rabbit serum. To examine the specificity of this response, progenitor cells giving rise to megakaryocyte, granulocyte-macrophage, erythroid, and mixed-cell colonies were assayed after injection of various heterosera or saline. All four colony types increased in the serum-treated groups. Since the in vitro proliferation of hematopoietic progenitor cells is promoted by supernatants of mitogen-stimulated spleen cells, we hypothesized that the immune response following antiserum administration resulted in the in vivo activation of T lymphocytes which produced or led to the production of colony stimulating activities. To test this hypothesis, cyclosporin A, a preferential inhibitor of T lymphocyte function, was given to mice concurrently with antiserum and also added to spleen cell cultures in the presence of pokeweed mitogen. Cyclosporin A abrogated the antiserum- related increases in progenitor cell numbers in vivo and the production of colony stimulating activity in vitro. The results suggest that the immune response related to antiserum administration results in the in vivo production of hematopoietic colony stimulating activities that may be identical to those produced in vitro by mitogen-stimulation of spleen cells.
Clonal origin of human erythro-eosinophilic colonies in culture
Authors: Nakahata T , Spicer SS , Ogawa M 
Published: October 2019

Abstract
We have observed the presence of erythropoietic bursts containing eosinophils and their precursors in methylcellulose culture of human peripheral blood and marrow nucleated cells in the presence of erythropoietin and medium conditioned by phytohemagglutinin-stimulated leukocytes (PHA-LCM). It was possible to identify these bursts (colonies) in situ in methylcellulose culture on the basis of their unique red and black colors. Transmission electron microscopy revealed that the constituent erythroid and eosinophilic cells lay intermixed with each other, and through close intercellular connections formed compact colonies and bursts consisting of several sub-colonies. Differential counts of individual erythro-eosinophil colonies (EEo colonies) revealed only a small percentage of blast cells in most of the colonies. Replating experiments of single EEo colonies yielded only eosinophilic colonies and clusters and erythroid colonies. The clonal nature of the EEo colonies was documented by analysis of Y-chromatin- positive cells in individual EEo colonies derived from cocultures of male and female peripheral blood mononuclear cells. Comparison of conditioned media indicated that PHA-LCM is the best stimulator for EEo colonies. These studies suggest that the differentiation capabilities of the progenitors for EEo colonies are restricted to erythroid and eosinophilic differentiation.
A simple technique for preparation of young red cells for transfusion from ordinary blood units
Authors: Graziano JH , Piomelli S , Seaman C , Wang T , Cohen AR , Kelleher JF Jr , Schwartz E 
Published: October 2019

Abstract
We have developed a rapid and simple method for the isolation of relatively young cells from ordinary fresh or previously frozen blood units, using the IBM-2991 Blood Cell Processor. Based on in vitro measurements of red cell pyruvate kinase activity, the resolution of the method is excellent, comparable to that of the stractan discontinuous gradient system. In splenectomized patients with thalassemia major, the administration of the “youngest” 50% of blood units yielded 51Cr survival times of 40 and 42 days for fresh packed red cells and 41 and 43 days for previously frozen red cells.
Combination chemotherapy (M-2) protocol (BCNU, cyclophosphamide, vincristine, melphalan, and prednisone) for Waldenstrom macroglobulinemia: preliminary report
Authors: Case DC Jr 
Published: October 2019

Abstract
Fourteen consecutively referred, symptomatic patients with Waldenstrom's macroglobulinemia (ages 52–87 yr) have been treated with the 5-drug M-2 protocol (BCNU, cyclophosphamide, vincristine, melphalan, and prednisone). Three patients were previously treated and 11 patients were untreated. The majority of patients were symptomatic from hyperviscosity. All patients have responded to therapy. Two patients have achieved complete remissions and 12 patients partial remissions to date. None of the patients with symptomatic hyperviscosity has required plasmapheresis since therapy with the M-2 has been initiated. Lymphadenopathy, hepatosplenomegaly, and anemia have also responded to treatment. Follow-up data are limited, with survival from initiation of therapy with the M-2 ranging from 2+ to 35% mo (median 17+ mo) 2+-40+ mo from time of diagnosis). Combination chemotherapy for Waldenstrom's macroglobulinemia with the M-2 protocol appears to increase the response rate in patients with symptomatic disease. Further survival analysis will be carried out.