bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hydrogen Peroxide and Platelet Function
Authors: Canoso Rosa T. , Rodvien Robert , Scoon Kristine , Levine Peter H. 
Published: October 2019

Abstract
Hydrogen peroxide, at concentrations in the micromolar range, can influence platelet function. Although H2O2 causes no detectable platelet aggregation at these concentrations, it can aggregate platelets which have been previously exposed to any of several aggregating agents. H2O2 can enhance bath aggregation and the subsequent disaggregation of platelets, as initiated by ADP. Preexposure of platelets to H2O2 blunts the subsequent response to ADP. Washed platelets are susceptible to H2O2. Catalase-treated H2O2 has no effect on platelet function. H2O2 does not appear to act by altering either the aggregating agent or plasma thrombin generation. These data suggest that minute amounts of H2O2, which could theoretically be generated in vivo at sites of platelet plug formation, could play a regulatory role in the dynamics of growth and/or dissipation of the hemostatic plug. The blood granulocyte could participate in hemostasis and thrombosis via H2O2 generation.
Production of Colony-stimulating Factor by Malignant Leukocytes
Authors: Golde David W. , Rothman Belina , Cline Martin J. 
Published: October 2019

Abstract
There is considerable evidence supporting a role for colony-stimulating factor (CSF) as a humoral regulator of leukopoiesis. Data on CSF levels in the serum and urine of patients with leukemia and on the in vitro responsiveness of leukemic cells to CSF have suggested a basis for considering leukemia as a primary disorder of leukopoietic regulation. We examined the question of leukemic cell production of CSF. Conditioned medium from cultured leukemic cells was tested for colony-stimulating activity against normal human bone marrow using a two-layer agar colony assay technique. The cells from patients with acute myelogenous leukemia and a patient with chronic myelogenous leukemia in blast crisis did not elaborate CSF nor did acute lymphocytic leukemia cells. CSF production was documented with cells obtained from patients with chronic myelogenous leukemia in the chronic phase and two patients with acute myelomonocytic leukemia. In acute leukemia the cellular production of CSF correlated closely with morphologic and functional maturation along the monocyte-macrophage line. Evidence was obtained that the adherent cells within the leukemic population were primarily responsible for CSF production. We interpret these data to indicate that neoplastic hematopoietic cells may produce CSF in relation to their capacity for mononuclear leukocyte differentiation.
The Value of the Serum Vitamin B12 Level in Diagnosing B12 Deficiency
Authors: Pierce H. Irving , Hillman Robert S. 
Published: October 2019

Abstract
Serum vitamin B12 levels of 2523 individuals were measured using the hemoglobin-coated charcoal assay. In one hospital, the test was performed on 1698 patients under hematologic evaluation for erythrocytic abnormalities of all types, while 825 patients from five other hospitals were studied because of suspected B12 deficiency. The incidence of low serum vitamin B12 was surprisingly low for both groups (2.3% and 3.5%, respectively). The value of the test as a diagnostic tool was further reduced by two characteristics of physician performance. First, with those patients who demonstrated a clear-cut macrocytic anemia and were suspects for intrinsic factor deficiency (pernicious anemia), extensive evaluations for B12 malabsorption were usually carried out prior to the receipt of the low B12 level. Second, when a deficiency state was not suspected, the return of a low value did not reliably stimulate physicians to begin evaluation or institute therapy. This was true despite the presence of clinical evidence of a possible gastrointestinal abnormality in many of the patients.
DNA Polymerases in Normal and Leukemic Human Hematopoietic Cells
Authors: Coleman Mary Sue , Hutton John J. , Bollum F. J. 
Published: October 2019

Abstract
DNA polymerase activities were assayed in bone marrow cells and peripheral leukocytes from normal people and patients with acute myelogenous, chronic lymphocytic, and chronic myelogenous leukemia. Extracts of subcellular components were fractionated by velocity sedimentation through sucrose density gradients and assayed using activated DNA as template. Two major DNA-dependent DNA polymerases were found in human cells with molecular weights of approximately 50,000 and 200,000 daltons, respectively. The DNA polymerase of high molecular weight is located in the soluble cytoplasmic fraction and is inhibited by N-ethylmaleimide. The low molecular weight polymerase is detected in extracts of nuclei and in the soluble fraction. It is resistant to inhibition by N-ethylmaleimide. In all cell types tested, total DNA polymerase activities were much higher in cytoplasmic than in nuclear extracts. Lymphocytes purified from normal peripheral blood had three to four times as much of both the high and low molecular weight polymerase activities per cell as purified granulocytes. Leukemic myeloblasts had 10 to 20 times as much cytoplasmic DNA polymerase activity as more mature leukocytes from normal peripheral blood. In general, immature granulopoietic cells contained higher total DNA polymerase activities than more mature granulocytes, and the major increases in polymerase activities were in the high and low molecular weight cytoplasmic enzymes rather than in the nuclear enzyme.
Platelet Antiheparin Activity: Storage Site and Release Mechanism
Authors: Walsh Peter N. , Gagnatelli Giovanna 
Published: October 2019

Abstract
The platelet storage and release mechanisms for the heparin-neutralizing activity (HNA), adenosine diphosphate (ADP), serotonin, and lysosomal enzymes were investigated in normal human platelets and in platelets with defective storage or release of ADP and serotonin. The time course of release of HNA from normal washed platelets by thrombin and collagen was slower than that of serotonin. Lysosomal enzymes were not released by collagen from normal washed platelets, whereas under the same conditions HNA was released. In four of six patients with storage pool deficiency, the platelets contained normal amounts of HNA but definitely decreased amounts of ADP and serotonin, whereas in the remaining two patients the total contents of ADP, serotonin, and HNA were all definitely lower than normal. In four of six patients with storage pool deficiency, the amounts and per cents of total HNA released by collagen were normal, whereas the amounts and per cents of total ADP released were diminished compared with normal. Platelets from patients with the aspirinlike platelet release defect and from aspirin-treated normal subjects contained normal quantities of ADP, serotonin, and HNA, but HNA and ADP were not released in response to collagen. It is concluded that either HNA is stored in and released from dense granules by mechanisms different from those for ADP and serotonin, or that HNA is stored in and released from granules other than the dense granules, which contain ADP and serotonin and the α-granules, which contain lysosomal enzymes.
Bone Marrow Involvement in Hodgkin's Disease: Pathology and Response to MOPP Chemotherapy
Authors: Myers C. E. , Chabner B. A. , De Vita V. T. , Gralnick H. R. 
Published: October 2019

Abstract
Examination of the bone marrow biopsies of 174 patients with Hodgkin’s disease seen at the National Cancer Institute between 1965 and 1972 revealed tumor involvement of the marrow in 19 cases. Eighteen of the 19 patients were treated with intensive combination chemotherapy (MOPP), and 13 achieved complete remission; the median duration of remission was 25+ mo, and 49% of those at risk remained in continuous remission for at least 3 yr. In all patients with marrow involvement, marrow fibrosis due to increased collagen or reticulin was identified in the pretreatment specimen. Repeat biopsies following therapy revealed entirely normal marrow free of tumor and reticulin or collagen fibrosis in eight patients, although residual collagen was detected in three other patients. Pretreatment leukopenia (WBC less than 5000 cells per cu mm) was present in seven of the 18 patients treated with MOPP, and appeared to be associated with an increased risk of infection and a less favorable response to therapy. These results indicate that nonleukopenic patients with Hodgkin’s disease and bone marrow involvement can be safely and effectively treated with intensive chemotherapy, and that pathologic changes in the marrow, including diffuse myelofibrosis, are often reversible with such therapy.
Intracellular Lysozyme in Mature Neutrophils and Blast Cells in Acute Leukemia
Authors: Karle Hans , Hansen Niels Ebbe , Killmann Sven-Aage 
Published: October 2019

Abstract
Intracellular lysozyme (muramidase) activity was measured in leukemic blasts and mature neutrophilic granulocytes from 20 patients with acute myeloblastic and myelomonocytic leukemia and in 11 patients with acute lymphoblastic leukemia after differential centrifugation of cells in Ficoll and extraction of lysozyme with n-butanol. Considerable abnormalities in cellular lysozyme activity were found both in qualitative and quantitative terms. In contrast to normal myeloblasts, leukemic blasts of the myeloid series contained lysozyme in a considerable number of cases. Although no clear-cut distinction was seen, those patients with positive blast lysozyme reactivity tended to have the highest plasma lysozyme levels, whereas no good correlation was found between morphologic differentiation along myeloblastic or monocytoblastic lines of blasts and lysozyme reactivity. Calculations of the magnitude of lysozyme production in acute leukemias with high plasma lysozyme concentration was compatible with the hypothesis that in these cases lysozyme must be secreted by intact blasts and that, consequently, plasma lysozyme activity reflects the total leukemic cell mass. In mature neutrophilic granulocytes from patients with acute myeloblastic and myelomonocytic leukemia in relapse, the mean lysozyme activity was significantly decreased, although a great deal of variation was found. In remission, neutrophil lysozyme activity seemed to increase; among several possibilities this might be a reflection of different clones being operative in relapse and remission. In acute lymphoblastic leukemia, lysozyme activity in neutrophils was constantly low in relapse and increased to normal following induction of remission, which may be the main explanation of the low plasma lysozyme activity found in this type of acute leukemia. It is unexplained and puzzling why intraneutrophil lysozyme activity is low in a leukemic type where the myeloid cells are not believed to be primarily leukemic; one possible reason might be an effect of cell-to-cell interaction with the leukemic cell population.
Glycogen Metabolism in Glycogen-rich Erythrocytes
Authors: Moses Shimon W. , Bashan Nova , Gutman Alisa , Ockerman Per Arne 
Published: October 2019

Abstract
High concentrations of red blood cell glycogen were visualized by electron microscopy and demonstrated biochemically in amylo-1,6-glucosidase- and phosphorylase-deficient red blood cells. Glycogen concentration decreased as a function of cell age. Similar incorporation rates of 14C-U-glucose into glycogen were observed in amylo-1,6-glucosidase-deficient and normal erythrocytes, characterized by an initial rise, followed by a plateau formation reflecting a steady state between glycogen synthesis and breakdown. A different pattern of kinetics was observed in phosphorylase-deficient cells, which in view of the lack of the degradative enzyme showed a continuous linear increase in radioactive glycogen formation leveling off only after exhaustion of substrate. Evidence that in amylo-1,6-glucosidase-deficient red blood cells the main metabolic activity affects the outer branches of the glycogen molecule was obtained directly by β-amylolytic degradation of the radioactive glycogen molecule and indirectly by a chase experiment substituting radioactive with nonlabeled glucose. Normal glycogen synthetase activity was found in all cases of amylo-1,6-glucosidase examined except in one family in which an unexpected low affinity of the enzyme to glycogen was found. The observation that both amylo-1,6-glucosidase- and phosphorylase-deficient red blood cells retain the capacity to incorporate glucose into glycogen indicates that glycogen synthesis in erythrocytes proceeds along the UDPG glycogen synthetase pathway and is not a result of a reverse activity of any of the degradative enzymes.
Alterations of Granulopoiesis Following Chemotherapy
Authors: Greenberg Peter , Bax Ine , Mara Beth , Schrier Stanley 
Published: October 2019

Abstract
Clonal proliferation of marrow granulocytic progenitor cells (GPC) in vitro and the daily urinary output of granulocytic colony-stimulating factor (CSF) were determined in two patients with acute myeloid leukemia (AML) in remission and one patient with malignant lymphoma receiving monthly pulses of chemotherapy with cytosine arabinoside and 6-thioguanine. During and immediately following therapy, a marked decrease of granulocytic colony-forming capacity (CFC) occurred, with an increase and return to basal levels by 3-4 wk. In the AML patients, the proportion of GPC in DNA synthesis (GPC-S), as determined by the thymidine suicide technique, declined from basal levels (31%-39%) to 0%-26% after 2 days of treatment. This was followed by a sharp rise in GPC-S to 41%-75% 1-3 days posttherapy, with an oscillatory return of GPC-S to basal levels by 3-4 wk. In all courses a marked increase of urinary CSF output occurred during or 1 day posttherapy, concomitant with the rise of the proportion of GPC-S. In the lymphoma patient, an initially high proportion of marrow GPC-S and low CFC anticipated the severe neutropenia which followed therapy. These results provide a basis for determining the efficacy with which cytotoxic drugs destroy proliferative activity of GPC and for assessing the potential for hemopoietic toxicity following chemotherapy.
Effects of Hydrocortisone on the Yield and Bactericidal Function of Granulocytes Collected by Continuous-flow Centrifugation
Authors: Shoji Mamoru , Vogler William R. 
Published: October 2019

Abstract
The usefulness of granulocyte transfusions is in part dependent upon the number of granulocytes transfused. The invention of the continuous-flow cell separator has made it possible to obtain granulocytes from normal donors. Efforts to improve the yield are under study. This controlled study was undertaken to determine the effect of a single dose of hydrocortisone on granulocyte yield from volunteer donors and on granulocyte bactericidal function. Twenty-two normal volunteers were randomized between no therapy or a single intravenous injection of 120 mg/sq m of hydrocortisone 2 hr prior to initiation of a 4-hr leukapheresis using the Aminco cell separator operated at 750 rpm and a flow rate of 41 ml/min. Significant increases in granulocyte yield and reductions in lymphocyte and monocyte yields were obtained in the hydrocortisone-treated group. Granulocytes from each group were equally effective in the phagocytosis of yeast particles and in vitro bactericidal activity.
Polymorphonuclear Leukocytes Prepared by Continuous-Flow Filtration Leukapheresis: Viability and Function
Authors: Harris Michael B. , Djerassi Isaac , Schwartz Elias , Root Richard K. 
Published: October 2019

Abstract
Preparation of granulocytes for transfusion in high yield and relatively free of contamination by other cell types has been made possible by the technique of continuous-flow filtration leukapheresis (CFFL). Since previous work suggested that granulocytes collected in this manner may have impaired viability and function, a detailed study of the bactericidal, metabolic, and chemotactic properties of such cells was performed and compared to control cells obtained from the same donors prior to CFFL. The granulocyte percentage of the cell suspensions obtained by CFFL averaged 94.5% ± 1.5% compared to 82.5% ± 1.8% for the controls (p < 0.001) with viability of the PMNs determined by trypan blue exclusion being 97.5% ± 0.9% and 98.2% ± 0.5%, respectively. The phogocytic, metabolic (14C-I-glucose oxidation and protein iodination) and chemotactic properties of both cell types were equivalent in suspensions equalized for granulocyte content. These findings indicate that CFFL technique employed does not impair granulocyte viability or function in vitro. Studies of the in vivo survival and function of CFFL granulocytes are necessary to evaluate their efficacy in combating infection in severely leukopenic patients.
The Number of in Vitro Stem Cells in AKR Leukemic Mice
Authors: Chevalier Christiane , Gaillard Nadine , Frindel Emilia 
Published: October 2019

Abstract
The total number of in vitro stem cells (CFUc) is lower in AKR leukemic mice than in nonleukemic AKR mice of the same age. This decrease is caused by a drop in the bone marrow CFUcs which is not compensated for by an increase in the number of these cells in the spleen. This decrease in CFUcs is not due to the presence of leukemic cells in the cultures, nor to the age of the mice, nor to a modified response to the stimulating factor (CSF) of CFUcs in leukemic mice.
An Acquired Inhibitor of Fibrin Stabilization Associated With Isoniazid Therapy: Clinical and Biochemical Observations
Authors: Otis Peter T. , Feinstein Donald I. , Rapaport Samuel I. , Patch Mary Jane 
Published: October 2019

Abstract
A patient who bled seriously while taking isoniazid was found to have an inhibitor of fibrin stabilization. The bleeding appeared to cease soon after the isoniazid was discontinued, although the plasma still contained potent inhibitor activity. This activity gradually disappeared over several weeks. The inhibitor was precipitated at 50% saturation with ammonium sulfate, migrated in the beta area on zone electrophoresis, and was found in the second peak on Sephadex G-200 gel filtration. Inhibitor activity persisted after heating to 90°C. Fibrinogen isolated from the patient’s plasma lacked factor XIII activity but did not contain measurable inhibitor activity. When the rate of incorporation of 14C-putrescine into casein was utilized to study the kinetics of the inhibitor, it was shown that the inhibitor acted reversibly and that it competed with the amine donor, 14C-putrescine. The mechanism whereby isoniazid led to the development of the inhibitor is unknown.
Erythroid Colony Formation in Vitro by Dimethylsulfoxide-treated Erythroleukemic Cells
Authors: Goldstein Kenneth , Preisler Harvey D. , Lutton John D. , Zanjani Esmail D. 
Published: October 2019

Abstract
Friend leukemic cells grown in suspension culture with dimethylsulfoxide can be induced to respond to erythropoietin by increased synthesis of hemoglobin. Investigation was undertaken to determine if these erythroleukemic cells could be induced to form erythroid colonies in a plasma-clot system. This study demonstrates that culture for 24-48 hr in suspension in the presence of 2% dimethylsulfoxide affected these cells so that they then produced benzidine-staining erythroid colonies in the plasma-clot culture. The cells responded to erythropoietin in these cultures with an increase in the number of erythroid colonies.
Radiosensitivities of DNA molecules in lymphocytes from the circulating blood of man
Authors: Hashimoto Y , Ono T , Okada S 
Published: October 2019

Abstract
The radiosensitivities of DNA molecules from lymphocytes of human circulating blood were examined by alkaline sucrose gradient centrifugation. The single-strand breaks of DNA per rad, including the breaks formed under the present alkaline condition, were 1.2 plus or minus 0.1 breaks per 10–12 daltons DNA per rad. When the cells were transformed, the number of breaks was found to increase to 1.8 plus or minus 0.2 breaks per 10–12 daltons DNA per rad. The lymphocytes are capable of rejoining radiation-induced single-strand breaks of DNA. The rate of rejoining was dependent upon types of the suspending medium. The rate increased to ten times of that of the non-transformed cells upon transformation.
Impaired T-cell transformation in chronic lymphocytic leukemia (CLL): Demonstration of a blastogenesis inhibitory factor
Authors: Utsinger PD 
Published: October 2019

Abstract
A noncytotoxic serum factor was found in CLL serum which interfered with the response of normal lymphocytes to phytohemagglutinin (PHA) and pokeweed mitogen (PWM). This factor was not produced by B-lymphocytes during short-term culture. This factor may contribute to the impaired lymphocyte responsiveness in CLL. In five of six patients, T- lymphocytes which were purified by passage over nylon wool columns exhibited an impaired response to both PHA and PWM, suggesting that a dilutional effect alone does not fully explain the impaired lymphocyte transformation in CLL.
Accelerated myeloblast destruction and abnormal lysosome disruption in cultured bone marrow: association with indolent acute myelogenous leukemia
Authors: Branda RF , Jacob HS , Douglas SD , Moldow CF , Puumala RR 
Published: October 2019

Abstract
Despite no chemotherapy and a marrow morphologically typical of frank relapse, an acute myelogenous leukemia (AML) patient survived for nearly 1 yr. During this time she remained asymptomatic and maintained nearly normal levels of platelets and hemoglobin. Cytochemical and electron microscopic studies of her bone marrow in liquid culture revealed on several occasions a unique maturational sequence in that leukemic cells differentiated to form morphologically abnormal primary granules which appeared to rupture and cause cytolysis of these cells. In these cultures, blasts rapidly disappeared and were replaced by more mature granulocytes, in contrast to observations in cultures derived from five other patients with AML in relapse which showed persistently elevated blast counts with no evidence of maturation in vitro. These findings support the concept that in AML cell maturation is regularly impaired and in some cases also aberrant. In addition, the abnormal granule formation with autolysis of the leukemic cells observed in one patient may explain both the early cell death in vitro and this patient's relatively indolent clinical course. Similar in vitro studies may help predict atypical clinical courses in patients with AML and facilitate design of appropriate chemotherapy.
Human red cells protein kinase in normal subjects and patients with hereditary spherocytosis, sickle cell disease, and autoimmune hemolytic anemia
Authors: Beutler E , Guinto E , Johnson C 
Published: October 2019

Abstract
A somewhat simplified modification of a previously described method for the measurement of red cell membrane phosphorylation by ATP has been devised. Phosphorylation of membranes was linear with time for only 5- 10 min, and linearity with membrane concentration was observed only when assays were limited to short incubation times. Protein kinase activity of hereditary spherocytosis (HS) membranes was found to be normal. However, the average phosphorylation after 60 min incubation was less in HS membranes than in normal membranes. Findings similar to those in HS membranes were observed in sickle cell disease. The Km of red cell protein kinase for ATP is approximately 10(-5) M. Membrane phosphate binding sites are not saturated in either HS or normal membranes after 1 hr incubation with ATP. Approximately 27% of phosphorylating activity is lost after 1 hr incubation at 37 degrees C. GTP is a very inefficient phosphate donor. Under the conditions of measurement employed, the enzyme is slightly stimulated by 1 muM cAMP, but is not stimulated by 1 muM cGMP. Dephosphorylation of red cell membranes after labeling occurs at a similar rate in HS as in normal membranes. Although a mild abnormally in membrane phosphorylation is observed in HS, this could not be demonstrated to be due to a decrease in protein kinase activity or in alterations of its kinetic properties. The abnormally seen is not specific for HS.