bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abnormal clonogenic potential of T cells from multiple myeloma patients
Authors: Pilarski LM , Mant MJ , Ruether BA , Carayanniotis G , Otto D , Krowka JF 
Published: October 2019

Abstract
Peripheral blood lymphocytes (PBLs) from multiple myeloma patients are defective in both proportion and absolute numbers of OKT4+ cells and have a normal proportion but reduced absolute number of OKT8+ cells. To assess the functional capabilities of the T cells in myeloma patients, we cloned the T cells in PBLs using limiting dilution conditions in which 100% of OKT4+ and OKT8+ T cells in normal PBLs are able to form a clone. In contrast, the OKT8+ cells from PBLs of five of seven multiple myeloma patients were severely compromised in their clonogenic potential; only 7% to 25% of OKT8+ T cells appeared to give rise to a clone. Clonogenic potential of the OKT4+ cells in patients was more nearly normal. Analysis of two multiple myeloma patients with abnormally low numbers of T cells in PBLs revealed the existence of abnormalities in the progenitors of T cell clones. In both patients, two to three times as many T cell clones were observed as would have been expected based on the number of PBLs cultured at limiting dilution, indicating that OKT4′8- cells in PBLs are capable of giving rise to OKT4+ and, at lower frequency, to OKT8+ clonal progeny in vitro. We conclude that purely quantitative assessment of T cell subsets should be interpreted with caution, since proportionately normal numbers of OKT8+ cells in patient PBLs are seriously compromised in their ability to give rise to clonal progeny in vitro, and since there appears to be a OKT4′8- population of T cells in PBLs that are committed to become OKT4+ or OKT8+ T cells, but are unable to do so in vivo.
Hereditary factor VII deficiency: heterogeneity defined by combined functional and immunochemical analysis
Authors: Triplett DA , Brandt JT , Batard MA , Dixon JL , Fair DS 
Published: October 2019

Abstract
Twenty-six patients with hereditary factor VII deficiency (VII:C less than 10%) were evaluated using a panel of three thromboplastins of varying species and tissue origin in both coagulant and chromogenic assay systems. Normal values for the coagulation and chromogenic assays were 104% +/- 7% and 108% +/- 21%, respectively. Factor VII antigen was measured by a specific radioimmunoassay (normal, 470 +/- 112 ng/mL). The patients were divided into two groups based on the factor VII:Ag assay results. Group 1, 18 patients, had decreased levels of factor VII:Ag and group 2, eight patients, had normal levels of factor VII:Ag. The two groups were further subdivided on the basis of discrepant factor VII:C levels in the chromogenic and coagulant assays. The number of observed patterns of functional factor VII:C activity suggests a high degree of complexity of factor VII and thromboplastin interaction. Whereas no clinical bleeding was reported in any of the nine black patients evaluated, all Caucasians (16) and one Hispanic presented with mild to severe bleeding. Patients with factor VII:C greater than 10% using a human thromboplastin had a negative bleeding history, regardless of the activity measured with other thromboplastins. Factor VII activity measured with a human thromboplastin appears to correlate best with the clinical picture.
Hereditary methemoglobinemia due to cytochrome b5 reductase deficiency in blood cells without associated neurologic and mental disorders
Authors: Tanishima K , Tanimoto K , Tomoda A , Mawatari K , Matsukawa S , Yoneyama Y , Ohkuwa H , Takazakura E 
Published: October 2019

Abstract
Following the observation of two fraternal patients without neurologic symptoms, but with hereditary methemoglobinemia due to cytochrome b5 reductase deficiency in erythrocytic and nonerythrocytic cells, a familial study of their paternal and maternal relatives was undertaken. Ferrihemoglobin reductase activities in erythrocytes from the two patients were found to be impaired, and cytochrome b5 reductase activities in platelets and leukocytes were essentially absent. Any deficiencies of the enzyme activities seemed not to be found in nonhematopoietic cells. The enzyme activities in blood cells derived from the parents and some of their paternal and maternal family members showed levels intermediate between those of the patients and those of the normal control, which seemed to be heterozygous. The present cases did not belong to either the classic erythrocytic or the generalized type, and their enzyme deficiency was found rather to be restricted to their blood cells and not associated with neurologic and mental disorders. A necessity of diagnosis by tissues other than blood cells is discussed for a severe form of generalized-type hereditary methemoglobinemia with associated neurologic and mental disorders.
Chronic myelogenous leukemia: a multivariate analysis of the associations of patient characteristics and therapy with survival
Authors: Kantarjian HM , Smith TL , McCredie KB , Keating MJ , Walters RS , Talpaz M , Hester JP , Bligham G , Gehan E , Freireich EJ 
Published: October 2019

Abstract
The prognostic importance of patient pretreatment clinical and laboratory features was investigated in a group of 303 patients with Philadelphia chromosome-positive benign-phase chronic myelogenous leukemia. Intensive chemotherapy was given to 97 patients, and 78 underwent an early elective splenectomy. The overall median survival time, dated from hospital admission, was 39 months. Patient characteristics associated with shortened survival were age 60 years or older, black race, the presence of hepatomegaly, splenomegaly, symptoms, weight loss, and poor performance status. Adverse blood and bone marrow parameters were anemia, thrombocytosis or thrombocytopenia, a high proportion of peripheral blasts plus promyelocytes or of basophils, a high proportion of marrow blasts or basophils, decreased marrow megakaryocytes, and cytogenetic abnormalities in addition to the Philadelphia chromosome. Several of these factors were interrelated. A multivariate regression analysis demonstrated that the combination blood basophilia, race, additional cytogenetic abnormalities, age and marrow basophilia had the strongest predictive relationship to survival time. This resulted in a model segregating patients into low-, intermediate-, and high-risk groups, with median survivals of 53, 39, and 25 months, respectively. Another model was derived that did not include the marrow features and identified splenomegaly and platelet counts as adding to the prognosis prediction by blood basophilia, race, and age. Evaluation of the effect of therapy, after adjusting for differences in prognostic characteristics, showed that intensive chemotherapy was associated with survival prolongation among patients at intermediate and high risk of death. We conclude that a combination of pretreatment factors identifies different risk subcategories in patients with chronic myelogenous leukemia and is helpful in assessing overall prognosis and treatment effect.
Release of granulocyte-macrophage colony stimulating factors from major histocompatibility complex class II antigen-positive monocytes is enhanced by human gamma interferon
Authors: Piacibello W , Lu L , Wachter M , Rubin B , Broxmeyer HE 
Published: October 2019

Abstract
Human gamma interferon (HuIFN gamma) was assessed for its capacity to enhance release of granulocyte-macrophage colony stimulating factors (GM-CSF) from human peripheral blood monocytes. Natural HuIFN gamma (2 X 10(7) NIH reference units per milligram) at concentrations as low as 0.01 U/mL to 10 U/mL reproducibly enhanced release of GM-CSF. This enhancement was detected when T lymphocytes were depleted from monocyte preparations and when T lymphocytes and monocytes were depleted from populations of human bone marrow cells stimulated by monocyte- conditioned media to form colonies and clusters. T lymphocytes alone or in the presence of HuIFN gamma did not release GM-CSF. The enhancing activity of HuIFN gamma was removed by preincubating HuIFN gamma with neutralizing concentrations of monoclonal anti-HuIFN gamma, and recombinant HuIFN gamma mimicked the effects of natural HuIFN gamma, suggesting that the effects were due to HuIFN gamma itself. HuIFN gamma suppression of the release of inhibitory activity from monocytes was ruled out as a reason for the noted enhancing activity of HuIFN gamma. The enhancing activity of HuIFN gamma was confined to the MHC class II antigen-positive population of monocytes. Removal of these cells with monoclonal antibody plus complement (c') ablated the enhancing activity, high concentrations of certain monoclonal antibodies in the absence of c' blocked the enhancing activity and, when monocytes were sorted into MHC class II antigen-positive and -negative cells by fluorescence-activated cell sorting, it was only the positive cell fraction that responded to the enhancing activity of HuIFN gamma.
Rearrangements of chromosome 3 involving bands 3q21 and 3q26 are associated with normal or elevated platelet counts in acute nonlymphocytic leukemia
Authors: Bitter MA , Neilly ME , Le Beau MM , Pearson MG , Rowley JD 
Published: October 2019

Abstract
Fourteen patients with acute nonlymphocytic leukemia (ANLL) or dysmyelopoietic syndromes were found to have abnormalities involving the long arm of chromosome 3. In eight patients, the structural rearrangements involved both bands 3q21 and 3q26 and included t(3;3) (four patients), inv(3) (three patients), and ins(5;3) (one patient). Before treatment, seven of these eight patients had platelet counts above 100,000 per microliter, five had normal or elevated platelet counts, and four had significantly elevated platelet counts (600,000 to 1,731,000 per microliter). In each of the eight cases, normal or elevated platelet counts were associated with marked abnormalities of megakaryocytopoiesis, including increased numbers of megakaryocytes and numerous micromegakaryocytes. Classification within the French-American- British system was difficult in most of these cases; however, the leukemia in five of the eight patients with abnormalities of chromosome 3 that involved both bands 3q21 and 3q26 was classified as M4. The remaining six of the 14 patients had translocations between chromosome 3 and another chromosome. None involved both bands 3q21 and 3q26, and a break in either q21 or q26 was noted in only two patients. One of the six, who had ANLL (M4) with a normal platelet count, had a 3;5 translocation which involved band 3q25. These data suggest that in patients with ANLL, abnormalities of chromosome 3 which simultaneously involve bands 3q21 and 3q26 are associated with unusually high platelet counts.
Acute nonlymphocytic leukemia, preleukemia, and solid tumors following intensive chemotherapy of small cell carcinoma of the lung
Authors: Pedersen-Bjergaard J , Osterlind K , Hansen M , Philip P , Pedersen AG , Hansen HH 
Published: October 2019

Abstract
Six of 796 patients treated with intensive combination chemotherapy for small cell carcinoma of the lung developed overt acute nonlymphocytic leukemia (ANLL) (three patients) or preleukemia with severe refractory cytopenia and clonal cytogenetic abnormalities in bone marrow cells (three patients). The latent period to development of preleukemia or leukemia was less than two years in four of the six patients. The cumulative risk of preleukemia and leukemia according to a Kaplan-Meier estimate was 14.0% +/- 6.9% (mean +/- SE) four years after the start of treatment. The relative risk of overt ANLL was 77, since three cases were observed v 0.039 cases expected, based on the age- and sex- specific incidence of acute nonlymphocytic leukemia in the general Danish population. The risk of secondary solid tumors was not increased. The possible causes of the exceptionally early appearance and very high cumulative risk of leukemic complications found in the present study, as compared to previous experience in other malignant diseases, is discussed, including the implications for future therapy of patients with small cell lung cancer.
Microtubule organization of unstimulated and stimulated adherent human neutrophils in Chediak-Higashi syndrome
Authors: Pryzwansky KB , Schliwa M , Boxer LA 
Published: October 2019

Abstract
The numbers and length of centriole-associated microtubules of two patients with Chediak-Higashi syndrome (CHS) were examined. Detergent- extracted whole-mount preparations of adherent cells were studied by stereo high-voltage electron microscopy. Under conditions of random migration, neutrophils from both patients had a microtubule organization similar to that of the control; microtubule numbers (28 +/- 3) and length (7.0 +/- 2.8 micron) were within normal range. When cells were treated with phorbol myristate acetate (PMA), differences in the response of the two patients were noted. Neutrophils from patient No. 2 and the control showed a significant rise in numbers (38 +/- 5) and length (9.5 +/- 3.6 micron) of microtubules. In contrast, neutrophils from patient No. 1 were unresponsive to PMA treatment. Because vitamin C is used therapeutically in CHS patients and has been shown to correct microtubule-related cell function, neutrophils were exposed to ascorbic acid. A significant increase in microtubule numbers (35 +/- 6) was observed in cells from the control and patient No. 2 after ascorbate treatment; neutrophils from patient No. 1 showed no increase in microtubule numbers. While ascorbic acid did not affect microtubule length in the control cells, it caused a significant increase in microtubule length in neutrophils from both patients. Results suggest that adherent CHS neutrophils contain centriole-associated microtubules which are normal in number and length. However, differences between patients are observed regarding neutrophil responsiveness to stimuli which induce microtubule polymerization.
Identification and quantitation of protein S in human platelets
Authors: Schwarz HP , Heeb MJ , Wencel-Drake JD , Griffin JH 
Published: October 2019

Abstract
Gel filtered human platelets contaminated with less than 0.02% of plasma protein S contained 490 ng of protein S antigen per 3 X 10(8) platelets, equivalent to 2.5% of protein S in whole blood. Three patients with heterozygous plasma protein S deficiency, a congenital disorder associated with venous thrombotic disease, had platelet protein S antigen levels that were 40% of the mean platelet level in ten normal volunteers. In immunoblotting analysis, platelet protein S was indistinguishable from plasma protein S. Thrombin stimulation of platelets caused release of 63% of total protein S antigen and this release was abolished when platelets were preincubated with metabolic inhibitors. Thrombin effected limited proteolysis of platelet protein S and this reaction was inhibited by calcium ions. Immunofluorescent staining of platelets using protein S antibodies demonstrated that protein S colocalized with fibrinogen, an established alpha-granule protein. Thus, human platelets contain protein S in alpha granules that can be released by thrombin stimulation. The released protein S may bind to stimulated platelets and thereby promote and localize the anticoagulant activity of activated protein C on the platelet surface.
Human placental conditioned medium reverses apparent commitment to differentiation of human promyelocytic leukemia cells (HL60)
Authors: von Melchner H , Hoffken K 
Published: October 2019

Abstract
Using a system of sequential daughter cell transfers in semisolid medium, we have analyzed self-renewal and differentiation of human promyelocytic leukemia cells (HL60) in presence of all-trans retinoic acid and human placental conditioned medium (HPCM). We find that retinoic acid induces coordinated losses of self-renewal potential which are followed by phenotypic differentiation. The latter occurs as an all-or-none event and is reversible in the presence of HPCM. Thus, HL60 cells that apparently had terminally differentiated (as estimated by the ability to reduce nitroblue tetrazolium [NBT]) can lose their differentiation marker and reenter the proliferative pool.
Influence of oxygen tension on the viscoelastic behavior of red blood cells in sickle cell disease
Authors: Nash GB , Johnson CS , Meiselman HJ 
Published: October 2019

Abstract
Although the rheological behavior of sickle cell suspensions and of hemoglobin S solutions is known to be strongly dependent on oxygen tension (PO2), little data exist concerning the influence of PO2 on the viscoelasticity of individual HbSS RBC. We have used micropipette aspiration techniques to test the deformation response of both HbSS and control HbAA RBC over a wide range of PO2 at 23 degrees C. Sickled, spiculed HbSS cells were present for PO2 approximately less than 35 mm Hg; for a number of these cells, the deformation response was essentially elastic and an effective membrane rigidity (EMR) was calculated. EMR increased with decreasing PO2 and was approximately 5 to 50 times higher than the equivalent rigidity of oxygenated HbSS RBC. In addition, the rate of membrane deformation was very slow for sickled cells; the half-time for the deformation process increased as PO2 was lowered and was about two orders of magnitude longer than the equivalent time for normal RBC. Other sickled cells exhibited plastic deformation when subjected to comparable deforming forces and experienced irreversible membrane deformation and budding. At all PO2 levels tested, some HbSS RBC remained as discocytes; these cells had normal membrane elasticity and membrane viscosity. Furthermore, changes in PO2 did not affect the membrane properties of HbAA RBC. Thus, gross abnormalities in the deformation response of HbSS RBC were only detected after morphological sickling had occurred. These abnormalities most likely arose from changes in the cytoplasmic HbS viscoelasticity and, if present in vivo, would be expected to impair the flow of HbSS cells in the microcirculation.
HTLV-III infection after bone marrow transplantation
Authors: Antin JH , Smith BR , Ewenstein BM , Arceci RJ , Lipton JM , Page PL , Rappeport JM 
Published: October 2019

Abstract
We prospectively documented the development of a fatal, secondarily acquired severe immunodeficiency in a 19-year-old man who underwent uncomplicated bone marrow transplantation. He had no graft v host disease (GVHD) and had normal recovery of his immune system as determined by lymphocyte phenotyping, mitogenic responses of his peripheral blood lymphocytes, and his ability to secrete immunoglobulin. This alteration in immunity was associated with the acquisition of antibody to HTLV-III. His only risk factor for the development of HTLV-III infection was the transfusions he had received during the transplant and recovery period. Two of his 54 transfusions were from an asymptomatic individual at high risk for acquired immunodeficiency syndrome (AIDS), who was subsequently found to be seropositive for anti-HTLV-III and from whom HTLV-III was isolated. The loss of immunocompetence in patients without chronic GVHD disease is unusual, and our data support the view that this patient's immunodeficiency was due to HTLV-III. When bone marrow transplant recipients without chronic GVHD develop late opportunistic infections, consideration should be given to transfusion-associated AIDS.
Diaziquone given as a continuous infusion is an active agent for relapsed adult acute nonlymphocytic leukemia
Authors: Lee EJ , Van Echo DA , Egorin MJ , Nayar MS , Shulman P , Schiffer CA 
Published: October 2019

Abstract
Diaziquone given as a bolus has not been effective in patients with relapsed or refractory leukemia. Because of in vitro data suggesting enhancement of diaziquone-induced cytotoxicity for human and murine leukemia cells with increased duration of drug exposure and the relatively short terminal plasma half-life of diaziquone, 49 patients (34 acute nonlymphocytic leukemia [ANLL], six chronic myelogenous leukemia in blast crisis [CML-B], five acute lymphocytic leukemia [ALL], four 2 degrees ANLL) with leukemia were given diaziquone as a continuous infusion for seven days. The maximum tolerated dose was 28 mg/m2/d for seven days. The dose-limiting toxicity was the duration of bone marrow aplasia (median, 49 days to greater than 500 PMNs in responders; range, 28 to 101 days). Nonhematologic toxicity was minimal. Responses occurred only in patients with relapsed ANLL, of whom 26 were treated at effective doses. There were six complete responses (CR) (23%) and two partial responses (PR) (8%), although five of eight responders never achieved platelet counts greater than 100,000/microL. Thrombocytopenia in these patients was felt to be a manifestation of diaziquone effect, not persistence of leukemia. The median duration of CR was 195 days (range, 88 to 860+). One patient had active CNS leukemia at the start of treatment and has had a durable (28+ month) CR in both sites of disease. Diaziquone produced prolonged aplasia in patients with secondary ANLL and CML-B (five of ten patients died aplastic), whereas patients with ALL all had regrowth of leukemia and two failed to become aplastic. The lack of significant nonhematologic toxicity and the activity in patients with relapsed ANLL render diaziquone of interest as second-line therapy or consolidation therapy in first remission for patients with ANLL.
Sulfhydryl reducing agents and shape regulation in human erythrocytes
Authors: Truong HT , Ferrell JE Jr , Huestis WH 
Published: October 2019

Abstract
Metabolic crenation of red cells is reversible; on addition of nutrients, echinocytes recover the normal discoid shape. When the shape recovery takes place in the presence of reducing agents such as dithiothreitol (DTT), morphological change continues until the cells are stomatocytic. The degree of stomatocytosis varies, depending on the cell morphology when the nutrients and reducing agent are added. DTT has minimal effect on the shape of normal discocytes, but in its presence, mildly echinocytic cells become slightly cupped and advanced- stage echinocytes become severely stomatocytic. DTT must be present continuously for development and retention of stomatocytosis; echinocytes preincubated with or metabolically depleted in DTT do not become stomatocytic when supplemented in the absence of DTT, and DTT- induced stomatocytes revert to discocytes when the reducing agent is removed. DTT has no effect on adenosine triphosphate synthesis or equilibrium cell glutathione levels, and the induced stomatocytosis is not inhibited by excluding oxygen from cells during depletion. Spectrin phosphorylation and phosphate turnover are not affected by DTT. The echinocyte-to-discocyte transformation coincides with phosphorylation of membrane inner monolayer lipids (diacylglycerol to phosphatidic acid and phosphatidylinositol to phosphatidylinositol-4,5-bisphosphate). Overphosphorylation of these phospholipids is not responsible for the exaggerated shape recovery seen with reducing agents; phosphorylation of inner monolayer lipids proceeds identically in the presence and absence of DTT.