bluuebunny/crossref_metadata_2025_split huggingface dataset:
The pH dependence of quantitative ristocetin-induced platelet aggregation: theoretical and practical implications-a new device for maintenance of platelet-rich plasma pH
Authors: Coller BS , Franza BR Jr , Gralnick HR 
Published: October 2019

Abstract
Quantitative ristocetin-induced platelet aggregation of normal platelet- rich plasma (PRP) decreased with time after PRP preparation. An increase in p H of the PRP with time proved to be responsible for this finding. Diffusion of CO2from the plasma is the prime determinant of the change in pH. Since a complex combination of factors influences CO2 diffusion (surface area-to-volume relationship, capping, mixing, etc.) The change in pH is variable with time. Thus, quantitative ristocetin aggregation should be pH controlled. A simple device for maintaining PRP pH constant by control of the ambient pCO2 was designed and found effective in keeping both pH and quantitative ristocetin aggregation constant over a prolonged period of time. It can be adapted for use in platelet aggregation studies employing other reagents. The pH dependence of ristocetin-induced platelet aggregation is consistent with other data supporting an elctrostatic interaction between the platelet, von Willebrand factor, and ristocetin. We favor a model wherein ristocetin neutralizes some of the platelet's negative change and permits the von Willebrand factor to bridge sites on separate platelets to induce agglutination.
Immune function at diagnosis in relation to responses to therapy in acute lymphocytic leukemia of childhood
Authors: Jose DG , Ekert H , Colebatch J , Waters K , Wilson F , O'Keefe D 
Published: October 2019

Abstract
Tests of immune capacity were performed on blood from 49 children with newly diagnosed, untreated acute lymphocytic leukemia, and relation to prognosis was determined. Patients were treated with multiple-drug therapy and prophylactic cranial irradiation. Median follow-up time was 16 mo (range 10--37 mo). Principal unfavorable findings at diagnosis were absolute numbers of T lymphoid cells outside the range 850-- 2500/mul blood, absence of whole blood responses to phytohemagglutinin in vitro, a low titer of complexed antibody, and the presence in serum of free leukemic blast cell membrane antigen. Fourteen patients showed two or more unfavorable findings at diagnosis. Eleven of these have died. Four of the remaining 35 patients have died. A shorter duration of first remission was found among patients with abnormal numbers of T cells at diagnosis. The findings suggest that the immunologic capacity of the patient at diagnosis is an important determinant in responses to therapy.
Increase in circulating stem cells following chemotherapy in man
Authors: Richman CM , Weiner RS , Yankee RA 
Published: October 2019

Abstract
The number of circulating granulocytic stem cells (CFU-C) was determined by the in vitro methylcellulose technique in cancer patients receiving intermittent chemotherapy. In 17 patients studied prior to therapy, the median CFU-C concentration per 2 X 10(5) mononuclear cells plated was six, compared to a posttreatment median of 23 in 21 patients (p less than 0.001). Large numbers of stem cells were obtained by leukopheresis and cryopreserved with a 99.5% median CFU-C recovery. Cyclical changes in the concentration of stem cells with maximum values of 20 times baseline were demonstrated in a patient studied at weekly intervals during multiple courses of treatment. It was estimated that, at peak CFU-C concentrations, a quantity of stem cells equivalent to that present in a bulk bone marrow harvest could be obtained from the peripheral blood by a 17-liter pheresis. These results suggest that it may be practical to obtain an adequate number of stem cells from the peripheral blood to study autologous stem cell infusion as a means of averting myelosuppression in patients receiving intensive chemotherapy.
Decreased alpha globine mRNA in nucleated red cell precursors in alpha thalassemia
Authors: Natta CL , Ramirez F , Wolff JA , Bank A 
Published: October 2019

Abstract
The alpha thalassemias are associated with a decrease in alpha chain synthesis. Hemoglobin H (HbH) disease is a moderately severe form of alpha thalassemia characterized by the production of 5%--20% of HbH, while alpha thalassemia trait is a milder form of alpha thalassemia. In two patients with HbH disease, the ratio of alpha chain synthesis to beta chain synthesis (alpha/beta ratio) was decreased in both bone marrow cells and reticulocytes. When isolated mRNA from bone marrow cells and reticulocytes was translated in a heterologous cell-free system, the alpha/beta ratios were lower than the intact cell ratios. These findings were confirmed by hybridization of the mRNA of both marrow cells and reticulocytes using purified alpha and beta cDNA probes. In the intact cells of two patients with alpha thalassemia trait, the alpha/beta ratios were also decreased and were similar in marrow cells and reticulocytes. Cell-free studies of translatable mRNA also demonstrated decreased alpha/beta ratios, but, unlike the HbH studies, the cell-free alpha/beta ratios were similar to the intact cell ratios. One hybridization study utilizing peripheral blood mRNA had an alpha/beta ratio consistent with the cell-free ratios. These results indicated that, in both HbH disease and alpha thalassemia trait, there was decreased alpha globin mRNA present in both nucleated red cell precursors and reticulocytes. In addition, the data suggested that there may be translational mechanisms that operate in intact HbH cells which attempt to balance globin chain production. In alpha thalassemia trait cells, no such controls appeared to be active and globin chain synthesis was directly proportional to the amount of alpha and beta globin mRNA in the cells.
Platelet function in the Chediak-Higashi syndrome
Authors: Buchanan GR , Handin RI 
Published: October 2019

Abstract
Platelet function studies were performed on two patients with the Chediak-Higashi syndrome, one of whom had a history of easy bruising unrelated to thrombocytopenia. Both patients had prolonged bleeding times, abnormal platelet aggregation, and a defect of platelet storage granules, manifested by reduced platelet ADP, an increased ATP/ADP ratio, increased adenine nucleotide specific radioactivity after 3H- adenine labeling, and decreased platelet uptake of radioactive 5- hydroxytryptamine. These findings confirm preliminary data in animals with the Chediak-Higashi syndrome, provide and explanation for impaired primary hemostasis in these patients, and illustrate another disorder in which platelet storage-pool deficiency occurs.
Insulin binding of acute lymphocytic leukemia cells
Authors: Esber EC , Buell DN , Leikin SL 
Published: October 2019

Abstract
Because of differences in insulin binding of cultured lymphoic cell lines, T- and B-cell surface receptor and 125I-insulin binding studies were performed on the bone marrow and peripheral blood leukocytes of 13 children with active acute lymphocytec leukemia. Based on surface receptors, nine patients had null-cell disease and four had T-cell disease. The mean per cent insulin binding of the bone marrow cells from the null-cell patients was 10.0% +/- 8.1 and from the T-cell patients was 0.18% +/- 0.13. The mean insulin binding of the cell suspensions of the peripheral blood from the null-cell patients was 7.3% +/- 7.5 and 0.07% +/- 0.06 from the T-cell patients. Displacement studies with nonradioactive insulin indicated that null leukemic cells bore specific binding sites. These results indicated that there may be metabolic as well as surface membrane heterogeneity among the acute lymphocytic leukemias of childhood.
Familial deficiency of glutathione reductase in human blood cells
Authors: Loos H , Roos D , Weening R , Houwerzijl J 
Published: October 2019

Abstract
A virtually complete absence of glutathione reductase activity was found in the erythrocytes of all three children (one male, two females) from a consanguineous marriage. Intermediate values were found in the erythrocytes of both parents. The enzyme activity could not be restored either by addition of FAD in vitro or by administration of riboflavin in vivo. The amount of reduced glutathione in the erythrocytes was normal in each case. Severely diminished glutathione stability during incubation with acetylphenylhydrazine was observed in the erythrocytes of the siblings, as well as intermediate stability in the parents' red cells. Clinically, this deficiency was manifested by hemolytic crises after eating fava beans in the eldest daughter (patient), and possibly by cataracts in her own and in her brother's eyes. Very low activities of glutathione reductase were also found in the leukocytes of this family: 13%-15% of normal values for the children and 64%-66% for the parents. Moreover, the same deficiency was found in the purified white blood cells of the propositus: 8% of normal values in the polymorphonuclear (PMN) cells, 4% in the lymphocytes, and 15% in the monocytes, together with 11% in the platelets. Finally, we found an abnormal oxygen consumption of the propositus' PMNs after phagocytosis of zymosan particles, suggesting that the glutathione reductase reaction was involved in the bactericidal capacity of these cells.
Factor XI activity and factor XI antigen in homozygous and heterozygous factor XI deficiency
Authors: Rimon A , Schiffman S , Feinstein DI , Rapaport SI 
Published: October 2019

Abstract
A relatively potent antiserum against highly purified, unactivated human factor XI antigen was raised in a rabbit. This antiserum, after concentration, neutralized 50% of the factor XI clotting activity of a standard normal plasma at an antiserum dilution of 1/900. The antiserum was used in a neutralization-inhibition assay to study the relation between factor XI clotting activity and factor XI antigen in plasma from ten unrelated patients with homozygous factor XI deficiency and from 12 heterozygous family members of these patients. No evidence of factor XI antigen significantly in excess of factor XI activity was found in either group. All data to date have been consistent with the hypothesis that hereditary factor XI deficiency represents a genetic disorder resulting from the absence of factor XI molecule. Severity of bleeding in factor XI deficiency could not be correlated with the level of factor XI activity or factor XI antigen.
Decreased nucleotide and serotonin storage associated with defective function in Chediak-Higashi syndrome cattle and human platelets
Authors: Bell TG , Meyers KM , Prieur DJ , Fauci AS , Wolff SM , Padgett GA 
Published: October 2019

Abstract
Prolonged mean template bleeding time of 14 min observed in seven cattle with the Chediak-Higashi syndrome (CHS) prompted the examination of platelet function in these animals. There was no distinguishable difference in concentration of circulating platelets between CHS and control cattle. CHS bovine platelets failed to aggregate in vitro in response to concentrations of acid-soluble collagen which induced aggregation in all normal samples. The primary platelet response to 5 muM ADP was normal in CHS cattle. A markedly decreased amount of serotonin (1.2% of normal) was detected in CHS bovine platelets. Bovine CHS platelet ATP and ADP contents were significantly less than normal, and the ATP/ADP ratios were 5.04 in normal and 29.38 in CHS platelets. Results of these animal investigations prompted a similar study of two patients with CHS. In humans, an increased bleeding time greater than 15 min and an in vitro impaired aggregation response to acid-soluble collagen and 5 muM adrenaline were discovered. Both ATP and ADP were reduced in CHS human platelets, and the ATP/ADP ratio was 3.96, compared to a ratio of 1.52 for platelets of two normal subjects. These findings suggested the presence of a “storage pool disease” of CHS platelets.
Heterogeneity of immunologic markers and surface morphology in childhood lymphoblastic lymphoma
Authors: Jaffe ES , Braylan RC , Frank MM , Green I , Berard CW 
Published: October 2019

Abstract
The neoplastic cells from seven patients with childhood lymphoblastic lymphoma were studied for cell surface markers and surface morphology in the scanning electron microscope (SEM). The cells were studied for surface immunoglobulin (Slg), complement receptors (EAC), receptors for cytophilic antibody (IgGEA), and nonimmune rosette formation with sheep red blood cells (E). In one patient the cells exclusively bound E, suggesting a T-lymphocytic origin. In two patients the cells bound EAC, but demonstrated no other B-lymphocytic markers. In two patients no markers were detected, and in two patients receptors for both E and EAC were demonstrated. Additional studies in one of these patients permitted simultaneous demonstration of both markers on the same neoplastic cells. The neoplastic cells were also examined by SEM after fixation and critical point dehydration. No consistent surface morphology was observed. In four patients the cells were predominately smooth, whereas in two patients variable numbers of surface microvilli were present. A correlation of the surface features with membrane markers could not be established. A comparison of the surface markers with clinical and cytologic features revealed clinical homogeneity in spite of the heterogeneous immunologic markers. This heterogeneity was most likely a reflection of neoplastic alteration and disordered differentiation of the cells. The observation of complement receptors on the cells of four cases is a feature not previously reported in this disease and should be investigated in other presumed T-cell malignancies.
A comparison of granulopoiesis in culture from blood and marrow cells of nonleukemic individuals and patients with acute leukemia
Authors: Tebbi K , Rubin S , Cowan DH , McCulloch EA 
Published: October 2019

Abstract
The objective of this study was to compare the concentration of committed granulopoietic progenitor cells (CFU-C) in marrow and blood. For individuals without leukemia, a highly significant correlation was observed between the concentration of CFU-C obtained from the two sites. However, CFU-C in blood had a slower sedimentation velocity than that reported for marrow and were found not to be in the DNA synthetic phase of the cycle using the tritiated thymidine suicide tehcnique. In patients with acute leukemia, no correlation was observed between concentrations of CFU-C in marrow and peripheral blood, regardless of whether the patients were newly diagnosed, in remission, or in relapse. We concluded that studies of the peripheral blood do not yield the same information in respect to granulopoietic progenitor cells as do studies of the marrow.
Fetal hemopoiesis in diffusion chamber cultures. III. The effect of neutropenia
Authors: Symann M , Quesenberry P , Fontebuoni A , Howard D , Ryan M , Stohlman F Jr 
Published: October 2019

Abstract
Proliferation and differentiation of granulocytes, macrophages, and both myeloid committed (CFC) and pluripotent (CFU) stem cells in diffusion chamber (DC) cultures of fetal liver were studied in order to evaluate the role of circulating humoral factors in the control of fetal myelopoiesis. When DC with fetal liver cells were implanted into mice rendered neutropenic by pretreatment with cyclophosphamide, more granulocytes and CFC were produced through day 10 as compared to DC implanted into saline pretreated control hosts. A difference in CFU recovery from fetal liver suspensions grown in DC implanted into neutropenic and control hosts was not seen until day 10. Serum CSF concentrations were increased in neutropenic as compared to control host mice 2 and 3 days after implantation of DC. Levels of serum inhibitors of colony growth showed marked variability but, in general, were similar in both groups. These data provide evidence that fetal CFC and fetal myelopoiesis are influenced by a circulating humoral factor present in neutropenic serum. CSF may be the factor, although the data presented in this paper do not establish this with any certainty.
The biochemical basis of nitroblue tetrazolium reduction in normal human and chronic granulomatous disease polymorphonuclear leukocytes
Authors: Baehner RL , Boxer LA , Davis J 
Published: October 2019

Abstract
Normal human polymorphonuclear leukocytes (PMN) placed in anaerobic chambers reaching pO2's of less than 5 mm Hg fail to generate O2-, iodinate ingested particles, and stimulate glucose-1–14C oxidation through the hexose monophosphate shunt. The observation that anaerobic cells are incapable of generating O2- or reducing nitroblue tetrazolium (NBT) to formazan supports the idea that NBT reduction in phagocytizing PMN is due exclusively to oxygen-dependent O2- generating oxidase which is deficient in chronic granulomatous disease leukocytes, despite their hyperphagocytic capacity.
5-Azacytidine (NSC 102816): a new drug for the treatment of myeloblastic leukemia
Authors: Vogler WR , Miller DS , Keller JW 
Published: October 2019

Abstract
The pyrimidine analog, 5-azacytidine (NSC 102816), was administered by continuous intravenous infusion in Ringer's lactate in increasing doses to sets of patients with metastatic cancer to establish a dose sufficient to produce mild toxicity. Twenty-one patients (23 trials) were treated with doses of 50–200 mg/sq/m/day for 5 days every 2–4 wk. Nausea and vomiting were moderate and easily preventable. Doses of 100- 200 mg/sq/m for 5 days every 14 days produced granulocytopenia, usually after two courses. Less toxicity was observed when courses were given every 21–28 days. Forty-five patients with previously treated and refractory acute myeloblastic leukemia were treated. The majority received doses of 150 mg/sq m for 5 days every 2 wk. Eleven (24%) complete remissions and four partial remissions were observed. The number of courses to achieve remission averaged three and required an average of 59 days. Nine patients with blastic crisis of chronic myeloblastic leukemia and four with refractory acute lymphoblastic leukemia failed to respond. 5-Azacytidine administered by continuous infusion is well tolerated and is an active compound in acute myeloblastic leukemia.
Human acute myelomonocytic leukemia: serologic studies with simian antisera
Authors: Mohanakumar T , Miller DS , Metzgar RS 
Published: October 2019

Abstract
Simian antisera to human leukemia cells were able to distinguish antigens specific for lymphocytic types of leukemia from those expressed on certain myeloid leukemia cells. In this investigation, cells from acute myelomonocytic leukemia patients (AMML) were examined for their membrane-associated leukemia antigens. Simian antisera to both lymphocytic and myelogenous leukemia cells lysed cells from AMML donors. Monkey antisera to AMML cells, by direct microcytotoxicity testing, were cytotoxic for cells from all AMML patients, as well as for cells of certain patients with myeloid leukemia. Cells from patients with lymphatic leukemia were nonreactive. However, absorption studies indicated an antigen present on cells from patients with chronic lymphocytic leukemia which cross-reacted with AMML cell antigens. Sequential analyses of the serologic reactivity of cells from AMML patients undergoing chemotherapy corresponded with the clinical course of the patient, even though there was little correlation between the percentage of blast cells present and the per cent cytotoxicity with the antisera. At certain times a higher percentage of seropositive cells could be detected over that seen on morphological evaluation. The estimation of leukemic cells by serologic means could aid in the diagnosis and management of AMML patients during chemotherapy.
Successful bone marrow transplantation against mixed lymphocyte culture barrier
Authors: Feig SA , Opelz G , Winter HS , Falk PM , Neerhout RC , Sparkes R , Gale RP 
Published: October 2019

Abstract
If bone marrow transplantation is to become widely applicable in the treatment of patients with leukemia and aplastic anemia, the necessity to have a perfectly histocompatible donor must be overcome. In an effort to define the roles of HL-A type and mixed lymphocyte culture (MLC) reactivity in the determination of successful engraftment and the occurrence of graftversus-host disease (GVHD), we have attempted transplantation of a child with acute myeloblastic leukemia (AML) using an HL-A identical, MLC-reactive sibling donor. Successful engraftment has been accomplished, as documented by the appearance of multiple donor genetic markers in the recipient. There is no evidence of severe GVHD. The recipient is alive, without evidence of leukemia, and has returned to full activities 9 mo after transplantation. The recipient now produces lymphocytes, which have the MLC reactivity that characterize the donor's lymphocytes, rather than that of her own pretransplant lymphocytes. This experience demonstrates that successful bone marrow transplantation in patients with leukemia can be accomplished in the face of MLC reactivity.
Red cell membrane deformability: new data
Authors: Bull BS , Brailsford JD 
Published: October 2019

Abstract
Red cells arrested by fine fibers and subjected to drag forces in a moving stream of fluid can be stressed beyond the point of rupture. The technique, which is basically an in vitro analogue of the microangiopathic hemolytic state, thus permits a study of red cell behavior over the entire range of stress that the membrane can withstand. Measurements made by this approach show an exponential relationship between the velocity of fluid flow and the resultant membrane deformation. Such exponential membrane deformation is consistent with the morphology of red cell fragments and appears to explain their mechanism of formation.
Chromosomes and causation of human cancer and leukemia. XXI. Cytogenetically unusual cases of leukemia
Authors: Sonta S , Oshimura M , Sandberg AA 
Published: October 2019

Abstract
Three male patients with leukemia were found with banding techniques to have unusual cytogenetic pictures in the cells of their marrow, spleen or blood. Case No. 1 (78 yr old) was that of a Ph1-negative CML with a missing Y in the blood (cultured without PHA) and marrow cells. The patient is still alive and responding to therapy. Case No 2 (54 yr old) was considered prior to admission to have either CML or AML, but was shown, in fact, to be in the blastic phase of CML; all the cells in his marrow and spleen were Ph1-positive, but with no evidence of a translocation. Other karyotypic findings (+8, +11, +13, +21) frequently encountered in the blastic phase of CML were present in the cells of this patient. Case No. 3 (50 yr old) with AML was shown to have a Ph1 resulting from a standard translocation, i.e., [t(9;22) (q34;q11)], in a substantial number of the cells in the marrrow and blood (cultured without PHA). The implications of these unusual findings are discussed in relation to the chromosomal pictures usually encountered in these states.