bluuebunny/crossref_metadata_2025_split huggingface dataset:
Significance of chromosome change to hematopoietic neoplasms
Authors: Chaganti RS 
Published: October 2019

Abstract
The application of banding techniques to the study of tumor chromosomes during the past 10 yr has yielded extensive data defining the types of chromosome changes that occur in human hematopoietic and other tumors. Chromosome changes characterize most tumors and exhibit a high degree of nonrandomness; in some tumors, this nonrandomness is defined by the tumor-inducing agents, while in others, it is defined by target cells of tumorigenesis. These observations led to the suggestion that chromosome abnormalities impart a selective advantage to the cells in which they occur and hence are of importance in the development of tumors. The mechanisms by which cells carrying chromosome abnormalities gain selective advantage are beginning to become apparent as the recently acquired data on the molecular genetics of neoplastic transformation are considered in conjunction with cytogenetic data. Activation of cellular oncogenes and overproduction of their products has been shown to be a key step in some types of neoplastic transformation. Chromosome abnormality is suggested to accomplish this step by either causing alterations in oncogene dosage or by activating normally quiescent oncogenes by bringing them into the transcriptional control of active genes. The paradigm for the latter model is the development of human and murine B-cell neoplasms in which specific translocations transfer c-myc from its constitutive site to a site next to the immunoglobulin genes. The chromosomal positions of several oncogenes have now been determined, and the elucidation of their fate in association with chromosome abnormalities in tumor cells can be expected to clarify mechanisms of oncogenesis.
Surface marker analysis of acute myeloblastic leukemia: identification of differentiation-associated phenotypes
Authors: Griffin JD , Mayer RJ , Weinstein HJ , Rosenthal DS , Coral FS , Beveridge RP , Schlossman SF 
Published: October 2019

Abstract
A series of monoclonal antibodies reactive with normal myeloid cells at different stages of differentiation (anti-MY4, -MY7, -MY8, -Mo1, -Ia) were used to characterize the leukemic cells of 70 patients with acute myeloblastic leukemia (AML). Sixty-two of the leukemias expressed a phenotype corresponding to a recognizable immature normal myeloid cell. These 62 cases could be divided into 4 phenotype groups, corresponding approximately to the normal CFU-C (group I, 21%), myeloblast (group II, 26%), promyelocyte (group III, 8%), and promonocyte (group IV, 45%). Morphological subtyping of these leukemias tended to agree with the immunologic phenotype, particularly with more “differentiated” morphological subtypes, such as acute monocytic leukemia or acute promyelocytic leukemia. However, each phenotype group contained more than one morphological type of AML, indicating that the level of differentiation of the surface membrane of AML cells may not always be concordant with morphology. The phenotype groups were also analyzed with respect to cytochemical staining patterns, age, the presence of Auer rods, and complete remission rates. Statistically significant differences among the groups were noted in the distribution of myeloperoxidase staining, nonspecific esterase staining, and Auer rods. The complete remission rates varied from 60% (groups III and IV) to 88% (group II). These results suggest that surface marker analysis in AML may be used as a highly reproducible classification system that will provide additional information about the leukemic cells in conjunction with morphological analysis.
Impaired granulocyte superoxide production and prolongation of the respiratory burst due to a low-affinity NADPH-dependent oxidase
Authors: Shurin SB , Cohen HJ , Whitin JC , Newburger PE 
Published: October 2019

Abstract
A 7-yr-old girl with self-limited pulmonary aspergillosis was found to have a defect in granulocyte superoxide production. Her cells produced superoxide at 3% of control rates in response to phorbol myristate acetate (PMA) and opsonized zymosan. Lag times for O-2 production were normal with PMA, opsonized zymosan, and concanavalin-A stimulation. Her granulocyte membranes depolarized in response to all of these stimuli. Superoxide produced by podosomes and a particulate fraction demonstrated an enzyme activity with a normal maximal velocity but a decreased affinity for NADPH. NADH-dependent superoxide production by particles was similar with patient and control material. The duration of superoxide production was prolonged in the patient's intact granulocytes and in the particulate fractions from her cells. Bacterial killing by the patient's granulocytes was initially low, but approached control values after 90 min of incubation. These results are explained by an enzyme activity that has a decreased affinity for its substrate and a decreased rate of inactivation. Family studies indicate an autosomal recessive mode of inheritance.
Prednisone pulse therapy for refractory myeloma
Authors: Alexanian R , Yap BS , Bodey GP 
Published: October 2019

Abstract
The utility of vindesine and a frequent prednisone schedule was evaluated in 70 patients with refractory myeloma. No patient responded to vindesine alone, but about one-fourth achieved significant tumor reductions from intermittent high-dose prednisone, either alone or in combination with vindesine. Forty-seven percent responded when prednisone pulses were combined with vincristine and doxorubicin, providing the best results yet achieved in our patients with refractory myeloma. In responding patients, remissions were of excellent quality and survival was prolonged significantly. These results supported the utility of a more frequent corticosteroid schedule with increased doxorubicin dose in patients with advanced and resistant multiple myeloma.
Differences among myeloproliferative disorders in the behavior of their restricted progenitor cells in culture
Authors: Croizat H , Amato D , McLeod DL , Eskinazi D , Axelrad AA 
Published: October 2019

Abstract
We have studied the behavior in culture of circulating restricted hemopoietic progenitor cells from patients with idiopathic myelofibrosis (IMF), polycythemia vera (PV), and essential thrombocytopenia (ET). We have found differences in circulating granulocyte-macrophage, erythroid, and megakaryocytic progenitors that appear to be specific for these chronic myeloproliferative disorders. In IMF, most affected were granulocyte-macrophage progenitor cells (CFU- C), which circulated in increased numbers and were heterogeneous in their sensitivity to the regulatory factor(s) present in phytohemagglutinin (PHA) stimulated T-lymphocyte conditioned medium (CM). Most CFU-C were either highly sensitive to, or independent from, stimulatory factors, while others showed normal sensitivity. In some IMF patients, circulating megakaryocytic progenitors (CFU-M) were present that were capable of giving rise to colonies in the absence of added CM or erythropoietin (EPO). In PV, we confirmed the presence of circulating erythroid progenitor cells that give rise to colonies in culture without the addition of EPO. The number of circulating CFU-C was normal and they responded normally to CM. In ET, failure to detect 7-day circulating restricted progenitor cells was a common observation; the level of other circulating restricted progenitors was in the low normal range. Thus, despite certain common features, including a primary lesion at the level of the pluripotential hemopoietic stem cell, the myeloproliferative disorders differ with respect to the behavior in culture of their circulating restricted progenitor cells. These results have led us to postulate a second regulatory lesion in the pluripotential stem cell that differs in these disorders and is expressed at the level of the respective restricted progenitor cells.
A monokine regulates colony-stimulating activity production by vascular endothelial cells
Authors: Bagby GC Jr , McCall E , Bergstrom KA , Burger D 
Published: October 2019

Abstract
Human umbilical vein endothelial cells were cultured in supernatants of peripheral blood monocytes that had been cultured for 3 days with and without lactoferrin. Colony-stimulating activity (CSA) was measured in supernatants of the endothelial cell cultures and appropriate control cultures using normal, T-lymphocyte-depleted, phagocyte-depleted, low- density bone marrow cells in colony growth (CFU-GM) assays. Monocyte- conditioned medium contained a nondialyzable, heat labile factor that enhanced 4–15--fold the production of CSA by endothelial cells. The addition of lactoferrin to monocyte cultures reduced the activity of this monokine by 69%. Lactoferrin did not inhibit CSA production by monokine-stimulated endothelial cells. Therefore, vascular endothelial cells are potent sources of CSA, the production of CSA by these cells is regulated by a stimulatory monokine, and the production and/or release of the monokine is inhibited by lactoferrin, a neutrophil- derived putative feedback inhibitor of granulopoiesis. Inasmuch as a similar monokine is known to stimulate CSA production by fibroblasts and T lymphocytes, we suggest that mononuclear phagocytes play a pivotal role in the regulation of granulopoiesis by recruiting a variety of cell types to produce CSA.
High serum colony-stimulating activity of leukocytopenic patients after intravenous infusions of human urinary colony-stimulating factor
Authors: Motoyoshi K , Takaku F , Miura Y 
Published: October 2019

Abstract
Eight adult patients suffering from leukocytopenia have been injected by droplet intravenous infusions with partially purified human urinary colony-stimulating factor (CSFHU), which stimulated human monocytes to produce colony-stimulating activity (CSA) in vitro. Three of eight patients were injected with low-dose CSFHU and five with high-dose CSFHU. The infusion of high-dose CSFHU led to a slightly earlier rise in absolute neutrophil counts and a higher CSA level in the serum, as compared to noninjected leukocytopenic patients. There was little toxicity associated with it. Human urinary colony-stimulating factor used in the clinical studies did not have any CSA in vitro in the presence or absence of the patients' sera. These data may suggest that the intravenous infusion of CSFHU increased the serum CSA level, probably through the stimulation of CSA-producing cells in vivo.
Leukocyte interferon-induced myeloid cytoreduction in chronic myelogenous leukemia
Authors: Talpaz M , McCredie KB , Mavligit GM , Gutterman JU 
Published: October 2019

Abstract
We investigated the antiproliferative effect of partially purified human leukocyte interferon (HuIFN-alpha) given in a dose of 9–15 X 10(6) U daily by intramuscular injection to 7 patients with chronic myelogenous leukemia (CML). Hematologic remission of the disease was obtained in 5 patients. Among the responding patients, the mean white blood cell count decreased from 97.4 X 10(3)/cu mm (range from 35 X 10(3)/cu mm to 239 X 10(3)/cu mm) to 4.2 X 10(2)/cu mm (range from 3.0 X 10(3) to 7.9 X 10(3) cu/mm). Parallel reduction occurred in serum B12, from a mean of 1,435 pg/ml to a mean of 726 pg/ml, and lactate dehydrogenase levels, from a mean of 325 mU/ml to 112 mU/ml. Enlarged spleens decreased in 3 of 3 patients. The 5 responding patients have been maintained on HuIFN-alpha, 3 X 10(6) U daily or every other day, for 6+-35+ wk.
Induction of differentiation of human acute myelogenous leukemia cells: therapeutic implications
Authors: Koeffler HP 
Published: October 2019

Abstract
A prominent phenotypic abnormality of human acute myelogenous leukemia cells is the inability of the cells to differentiate to functional mature cells; instead, the cells are blocked at an early stage of development and remain in the proliferative pool and rapidly accumulate. Investigation of the induction of myeloid leukemic cell differentiation has made recent advances with the development of several human myelogenous leukemia cell lines. The lines provide models to study the biology of myeloid differentiation and to identify inducers of differentiation of myeloid leukemic blood cells. This review critically examines the inducers of leukemic cell differentiation and their potential therapeutic importance.
Hemolytic anemia, recurrent metabolic acidosis, and incomplete albinism associated with glutathione synthetase deficiency
Authors: Prchal JT , Crist WM , Roper M , Wellner VP 
Published: October 2019

Abstract
The clinical and laboratory features of a 3-mo-old black male infant with glutathione (GSH) synthetase deficiency of the generalized type was evaluated. Partial albinism, brisk hemolytic anemia, recurrent febrile episodes, and mental retardation were noted. Also, severe recurrent metabolic acidosis and marked oxoprolinemia and oxoprolinuria were found in the proband but not in his first-degree relatives. The relationship of these disease manifestations to the underlying metabolic defect is discussed.
A proposal for smoldering adult T-cell leukemia: a clinicopathologic study of five cases
Authors: Yamaguchi K , Nishimura H , Kohrogi H , Jono M , Miyamoto Y , Takatsuki K 
Published: October 2019

Abstract
We have observed five patients with smoldering adult T-cell leukemia (ATL) who had skin lesions as premonitory symptoms. The illness developed slowly, but flared up after several years. Skin lesions appeared in the form of erythema, papules, or nodules. Infiltration of the skin by ATL cells was slight, and the proportion of ATL cells in the peripheral blood was 0%-2%. The serum lactate dehydrogenase (LDH) value was within normal range and was not associated with hypercalcemia; lymphadenopathy, hepatosplenomegaly, and bone marrow infiltration were very slight. In most cases, hypergammaglobulinemia was seen, and in one case, monoclonal hypergammaglobulinemia was observed. All five patients had lived in an area in which ATL was endemic, and their anti-ATLA antibodies were positive; none had ever received a blood transfusion. One patient developed typical ATL after more than 13 yr of illness and died of renal insufficiency. Another patient developed typical ATL after 5 yr of illness and died of cryptococcus meningitis. Based on clinical and pathologic differences, we believe that these cases should be distinguished from typical ATL cases for the purposes of prognosis and treatment.
Additional glycoprotein defects in Bernard-Soulier's syndrome: confirmation of genetic basis by parental analysis
Authors: Berndt MC , Gregory C , Chong BH , Zola H , Castaldi PA 
Published: October 2019

Abstract
The glycoprotein profile of Bernard-Soulier platelets was examined by labeling washed platelets with periodate 3H-sodium borohydride, a procedure that labels greater than 30 glycoproteins on the membrane surface of normal platelets. Three Bernard-Soulier patients were studied; two were siblings and the third was unrelated. The platelet protein and glycoprotein profiles were evaluated under nonreduced and reduced conditions using 5%-15% exponential SDS-polyacrylamide gel electrophoresis. The two siblings completely lacked glycoprotein Ib (GPIb). The unrelated patient had congruent to 7% of the normal level. This was confirmed by two-dimensional nonreduced-reduced SDS- polyacrylamide gel electrophoresis, a procedure that allows clear separation of the disulfide-linked subunits of GPIb, GPIb alpha (mol wt 145,000), and GPIb beta (mol wt 25,000) from other membrane glycoproteins. On one-dimensional analysis, Bernard-Soulier's syndrome (BSS) platelets also lacked the peripheral membrane glycoprotein, GPV (mol wt 82,000) and a low molecular weight glycoprotein, GPIX, (nonreduced or reduced, mol wt congruent to 22,000). The two- dimensional gel system also revealed the absence of a minor glycoprotein with a molecular weight of congruent to 100,000 (GP 100). Quantitation of these proteins solubilized from electrophoretograms showed that the siblings' parents had congruent to 50% levels of GPIb, GPIX, and GP 100. A monoclonal antibody against glycoprotein Ib, FMC 25, was negative by immunofluorescence against Bernard-Soulier platelets and immuneprecipitated both GP Ib and GPIX from Triton X100 solubilized, labeled platelets. The combined results suggest that the apparent genetic absence of multiple proteins in Bernard-Soulier platelets is due, in part, to the presence in normal platelets of a tight membrane complex between glycoprotein Ib and at least one of the other absent glycoproteins.
Studies on mitochondrial and cytoplasmic malate dehydrogenase in childhood myelodysplastic syndrome
Authors: Muchi H , Yamamoto Y 
Published: October 2019

Abstract
Three cases of uncommon childhood hematologic disorders are reported. At presentation, one patient had refractory anemia with an excess of blasts (RAEB) with partial 7-monosomy and was reclassified into RAEB “in transformation” thereafter. Another case was diagnosed as acute myelogenous leukemia with complete 7-monosomy. The other case was diagnosed as RAEB “in transformation” without chromosome aberrations. The cytogenetic studies of the patients with 7-monosomy revealed abnormal karyotypes on bone marrow cells, but normal karyotypes on peripheral blood cells. Polymorphonuclear cells from the two patients with 7-monosomy revealed reduced mitochondrial malate dehydrogenase activity, but those from the patient with RAEB “in transformation” without chromosome aberrations did not. Cytoplasmic malate dehydrogenase activity, having been defined as located on chromosome 2, was within the normal range in those three patients. The decreased mitochondrial enzyme activity in the two patients with 7-monosomy would be a dosage effect of the chromosome aberration, but not caused by their hematologic disorders. The level of mitochondrial enzyme activity in the patients with 7-monosomy was reduced in polymorphonuclear cells, but not in mononuclear cells in peripheral blood. This fact would indicate that such chromosome evolution had involved myeloid cells only, but not lymphoid cells. Both enzymes from leukemic cells of four patients with active disease revealed much higher activities than controls, an expression of partially enhanced oxidative phosphorylation.
Inhibition of human lymphocyte proliferation by monoclonal antibody to transferrin receptor
Authors: Mendelsohn J , Trowbridge I , Castagnola J 
Published: October 2019

Abstract
A monoclonal antibody, 42/6, which blocks the binding of transferrin to its receptor on the cell membrane, inhibits proliferation of human lymphocytes stimulated by phytohemagglutinin. Anti-receptor antibody B3/25, which does not block transferrin binding, does not alter the mitogenic response. Addition of soluble iron, in the form of ferric nitrilotriacetic acid, results in partial reversal of inhibition. Lymphocytes in the quiescent phase of the cell cycle at the time of 42/6 antibody addition are unable to traverse S phase, whereas cells actively proliferating when antibody is added are sensitive to its inhibitory effects throughout all phases of the cell cycle. Inhibition is static rather than cidal, since it can be reversed by removal of antibody after up to 48 hr of exposure.
The effect of X chromosome inactivation on the inhibition of Plasmodium falciparum malaria growth by glucose-6-phosphate-dehydrogenase- deficient red cells
Authors: Roth EF Jr , Raventos Suarez C , Rinaldi A , Nagel RL 
Published: October 2019

Abstract
Previous data on in vitro culture of Plasmodium falciparum malaria demonstrated that red cell glucose-6-phosphate dehydrogenase deficiency (G6PD-) inhibited parasite growth in deficient hemizygous males. This study investigated the effect of heterozygosity for G6PD- on parasite growth. Blood was obtained from 8 female Sardinian G6PD- heterozygotes with G6PD normal cells ranging from 13% to 60%. For comparison, blood from a G6PD- hemizygous male, containing 100% deficient red cells, was mixed in different proportions with compatible normal blood. In both experiments, parasite growth was inhibited by the presence of deficient cells. In both cases, it was found that the inhibition could be explained by a simple dilution of normal cells by G6PD- cells. Thus, the typical female heterozygote is also protected to a significant extent. When considering the “malaria hypothesis” as it relates to G6PD, protection of the female heterozygote as well as the male hemizygote must be taken into account.
Removal of T cells from bone marrow for transplantation: a monoclonal antilymphocyte antibody that fixes human complement
Authors: Hale G , Bright S , Chumbley G , Hoang T , Metcalf D , Munro AJ , Waldmann H 
Published: October 2019

Abstract
Graft-versus-host disease is one of the major problems in clinical bone marrow transplantation. Many experiments in animals have shown that it could be greatly reduced if mature T lymphocytes were removed from the donor marrow. Here we describe a new rat monoclonal antibody, CAMPATH 1, which is suitable for depleting lymphocytes from human marrow grafts. CAMPATH 1 is an IgM that fixes human complement. It binds to both T and B lymphocytes and some monocytes but not to other hemopoietic cells. When peripheral blood mononuclear cells were treated with CAMPATH 1 and complement, more than 99% of lymphocytes were killed and viable T cells could no longer be detected. Under these conditions, in vitro multipotential erythroid and myeloid colony-forming cells were unaffected. As well as being used for in vitro treatment of bone marrow to remove T cells, CAMPATH 1 could potentially be applied to other experimental and clinical situations where depletion of lymphoid cells is required, including serotherapy to achieve immunosuppression for organ transplants or to treat lymphocytic leukemias.
Antithoracic duct lymphocyte globulin therapy of severe aplastic anemia
Authors: Camitta B , O'Reilly RJ , Sensenbrenner L , Rappeport J , Champlin R , Doney K , August C , Hoffmann RG , Kirkpatrick D , Stuart R , Santos G , Parkman R , Gale RP , Storb R , Nathan D 
Published: October 2019

Abstract
We performed a prospective randomized trial of antithoracic duct lymphocyte globulin (ATDLG), HLA-haploidentical marrow, and androgen (regimen ABA) versus androgen alone (concurrent STANDARD care controls) in 42 newly diagnosed individuals with severe aplastic anemia. ABA patients also were matched with patients from our preceding study (historical STANDARD care controls). Supportive care and pretreatment patient characteristics were the same in all groups. By life table analysis, 76% of patients receiving ABA are alive at 2 yr compared to 31% of the concurrent control group (p less than 0.002 versus ABA) and 19% of the historical controls (p less than 0.0001 versus ABA) given STANDARD care. ABA patients had greater hematologic improvement than either control group (p less than 0.001). However, improvement with ABA was often incomplete. Toxicity of ATDLG was considerable but manageable. Further studies to determine the mechanism of action and active component(s) of ABA are indicated.