bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differing responses of globin and glycophorin gene expression to hemin in the human leukemia cell line K562
Authors: Tonkonow BL , Hoffman R , Burger D , Elder JT , Mazur EM , Murnane MJ , Benz EJ Jr 
Published: October 2019

Abstract
The human leukemia cell line, K562, produces embryonic and fetal hemoglobins and glycophorin A, proteins normally associated only with erythroid cells. Hemoglobin accumulation is enhanced by exposure of the cells to 0.05 mM hemin. We have examined K562 cells before and after exposure to hemin to determine whether expression of these erythroid proteins was shared by all cells or confined to specific subpopulations. Globin gene expression was examined by quantitation of globin mRNA sequences, using a 3H-globin cDNA molecular hybridization probe. Constitutive cells produced globin mRNA, the content of which was increased 3–4-fold by hemin. Cell-to-cell distribution of globin mRNA was determined by in situ hybridization of 3H-globin cDNA to constitutive and hemin-treated K562 cells. Virtually all cells in the culture exhibited grain counts above background, indicating globin gene expression by all cells, rather than a confined subpopulation. Virtually all hemin-treated cells had 3–5-fold higher grain counts, indicating uniformly increased globin gene expression. The glycophorin content of K562 cells was estimated by fluorescence-activated cell sorting (FACS) of cells labeled with fluorescein-labeled antiglycophorin antiserum. The vast majority of constitutive cells contained glycophorin, but exhibited to apparent increase in glycophorin accumulation after hemin exposure. Thus, glycophorin and globin genes exhibited differential responses to hemin. These differences could reflect normal differences in the patterns of specialized gene expression in stem cells. Alternatively, different aberrations of gene expression could be occurring in response to the determinants of the neoplastic properties of K562.
Collection of pluripotential hematopoietic stem cells by cytapheresis
Authors: Lasky LC , Ash RC , Kersey JH , Zanjani ED , McCullough J 
Published: October 2019

Abstract
Successful complete hematopoietic reconstitution (CHR) using nonleukemic peripheral stem cells (PSC) after marrow ablation has been reported in animals but not man. Previous studies of cytapheresis products from humans, as a prelude to use for CHR, have documented the presence of committed myeloid (CFU-GM) and erythroid (BFU-E) precursors. We have examined mononuclear cell (MNC) products collected on the Fenwal CS3000 Blood Cell Separator for these plus the more primitive mixed (granulo-, erythro-, mono-, and megakaryocytic) cell colony-forming units (CFU-GEMM) and for various lymphocytic subpopulations (LSP). One to two-hour products contained 36 +/- 7 CFU- GEMM/10(6) MNC (mean +/- SE, n = 8) or 490 +/- 131/ml product. This compared favorably with blood (23 +/- .4/10(6) MNC or 46 +/- 8/ml, n = 14) and bone marrow (146 +/- 58/10(6) MNC, n = 12). Collection efficiency for E-rosette-positive cells approximated that for total lymphocytes and was variable for other LSP. Recovery of CFU-GEMM after freezing in 10% dimethylsulfoxide at a controlled rate and storage in liquid N2 was 54% +/- 8% (n = 8). Cytapheresis collection of large numbers of pluripotent hematopoietic precursors and demonstration of adequate recovery of these after cryopreservation, both previously unreported, are significant steps toward eventual CHR using nonleukemic PSC.
Two classes of murine granulocyte progenitor cells expressed in plasma clot diffusion chamber cultures
Authors: Steinberg HN , Page PL , Robinson SH 
Published: October 2019

Abstract
Two distinct classes of granulocyte progenitor cells present in normal mouse bone marrow are expressed sequentially in the vivo plasma clot diffusion chamber culture system. By several criteria, progenitor cells giving rise to granulocyte colonies on day 4 of culture (CFU-D4) are different from those giving rise to colonies on day 7 (CFU-D7). These differences include: cell cycle activity as measured by in vitro incubation with cytosine arabinoside, residual concentration in the bone marrow after in vivo treatment of donor mice with cytosine arabinoside or methotrexate, resistance to osmotic lysis, size as determined by velocity sedimentation, and the morphology of the granulocyte colonies to which these cells give rise. The CFU-D7 appears to represent an earlier progenitor cell than the CFU-D4 in the differentiation pathway of the granulocyte and is analagous in many respects to the BFU-E in the erythroid pathway.
In vitro regulation of immunoglobulin synthesis after human marrow transplantation. II. Deficient T and non-T lymphocyte function within 3- 4 months of allogeneic, syngeneic, or autologous marrow grafting for hematologic malignancy
Authors: Witherspoon RP , Lum LG , Storb R , Thomas ED 
Published: October 2019

Abstract
Immunoglobulin secretion was studied in 37 patients between 19 and 106 days after allogeneic HLA-identical (30 patients), allogeneic one HLA- haplotype-identical (three patients), syngeneic (three patients), or autologous (one patient) marrow grafting. E rosette-positive (T) and E rosette-negative (non-T) peripheral blood mononuclear cells were cocultured with pokeweed mitogen for 6 days. Polyvalent immunoglobulin secretion was determined by counting plaque forming cells in a reverse hemolytic plaque assay. The number of antibody secreting cells in cocultures of autologous T and non-T lymphocytes was low in 40 of 44 tests conducted on samples from the 37 patients. Mononuclear or non-T cells from 38 of 40 tests failed to produce antibody when cultured with normal helper T cells. T cells from 23 of 37 tests failed to help normal non-T cells secrete antibody. T lymphocytes from 23 of 41 tests suppressed antibody production greater than 80% by normal T and non-T cells. The suppressor cells were radiosensitive in 17 of the 25 tests. The abnormal function of lymphocyte subpopulations in patients during the first 3 mo after syngeneic, allogeneic or autologous marrow grafting was similar regardless of the type of graft or the presence of acute graft versus host disease.
Prognosis of chronic lymphocytic leukemia: a multivariate survival analysis of 150 cases
Authors: Rozman C , Montserrat E , Feliu E , Granena A , Marin P , Nomdedeu B , Vives Corrons JL 
Published: October 2019

Abstract
A multivariate survival analysis by means of Cox's multiple regression model was performed on a series of 150 consecutive patients with chronic lymphocytic leukemia (CLL) from a single institution. In addition to the well established prognostic factors, such as anemia and thrombocytopenia, a marked prognostic value of the degree of absolute peripheral lymphocytosis emerged from this analysis. This was evident in the whole population as well as in low and intermediate risk groups of patients (Rai's stages 0, I, and II and International Workshop on CLL stages A and B), pointing out that different subsets of patients can be isolated within these groups.
Platelet-associated complement C3 in immune thrombocytopenic purpura
Authors: Myers TJ , Kim BK , Steiner M , Baldini MG 
Published: October 2019

Abstract
Platelet-associated C3 (PA-C3) was measured with a quantitative immunofluorescence assay. With this assay, PA-C3 levels were determined for 78 normal volunteers, 30 patients with immune thrombocytopenic purpura (ITP), and 20 patients with nonimmune thrombocytopenias. Platelet-associated IgG (PA-IgG) levels were also measured with our standard quantitative immunofluorescence assay. All patients with nonimmune thrombocytopenias and ITP in remission had normal PA-C3 levels. Twenty-four patients with active ITP were classified into 3 groups: 9 (38%) with increased PA-IgG and normal PA-C3 levels, 10 (42%) with elevated PA-C3 and PA-IgG levels, and 5 (20%) with increased PA-C3 values only. A direct correlation was found between PA-C3 and PA-IgG levels. PA-IgG levels were higher in the group of patients with elevated PA-C3 levels than in those with normal values. Platelet survival studied showed reduced survival times of 1.5--2.5 days for the 5 patients with elevated PA-C3 levels only. Elevated PA-C3 levels returned to normal in 7 ITP patients whose platelet counts increased in response to corticosteroid therapy or to splenectomy. Therefore, PA-C3 and PA-IgG assays can be used to identify patients with ITP, to follow their response to therapy, and to classify them into immunologic subgroups similar to red cell classification by Coombs'testing in immune hemolytic anemia.
Characteristics of bone marrow fibroblast colony-forming cells (CFU-F) and their progeny in patients with myeloproliferative disorders
Authors: Castro-Malaspina H , Gay RE , Jhanwar SC , Hamilton JA , Chiarieri DR , Meyers PA , Gay S , Moore MA 
Published: October 2019

Abstract
Chronic myeloproliferative disorders (MPD) are clonal diseases of the pluripotent hematopoietic stem cell frequently associated with myelofibrosis (MF). There is only indirect evidence indicating that the increased deposition of collagen in bone marrow matrix is a secondary phenomenon. A liquid culture system for cloning and growing bone marrow fibroblasts has permitted us to approach more directly the understanding of the pathogenesis of myelofibrosis by comparing the biophysical, growth, and functional characteristics of fibroblasts from normals, MPD patients without MF, and those with MF. In patients with MF, marrow fibroblast colony (CFU-F) formation could not be studied; fibroblasts were grown from marrow explants. CFU-E from normals and MPD patients exhibited similar cell density distribution and similar cell sedimentation rates. These similarities contrasted sharply with the differences seen when the erythroid and granulocyte-macrophage progenitors were studied by the same methods. There was a marked light density shift and a rapidly sedimenting shift of MPD hematopoietic colony-forming cells. Marrow fibroblasts from MPD patients with and without MF displayed the same in vitro growth characteristics as fibroblasts from normals. Both types of fibroblasts exhibited anchorage and serum dependence, and contact inhibition of growth. Marrow fibroblasts were also characterized for the presence and distribution of fibronectin and collagen types by immunofluorescent staining using monospecific antibodies. Extracellular matrix, membrane-, and cytoplasm- associated fibronectin, type I, type III, and type V collagen showed a similar staining pattern in both normal and myelofibrotic marrow fibroblasts. Plasminogen-dependent fibrinolytic activity elicited from normal and myelofibrotic marrow fibroblasts were equivalent. Chromosomal analysis of hematopoietic cells and marrow fibroblasts from Philadelphia chromosome positive chronic myelocytic leukemia patients with and without MF showed that the Philadelphia chromosome was present only in hematopoietic cells. The results of these studies taken together demonstrate that bone marrow collagen-producing cells from MPD patients with and without MF behave in vitro as do those from normals. These findings support the hypothesis that that the marrow fibrosis observed in patients with MPD results from a reactive process rather than from a primary disorder affecting the marrow collagen-producing cells.
Low serum thymic hormone levels in patients with chronic graft-versus- host disease
Authors: Atkinson K , Incefy GS , Storb R , Sullivan KM , Iwata T , Dardenne M , Ochs HD , Good RA , Thomas ED 
Published: October 2019

Abstract
We tested the hypothesis that chronic graft-versus-host disease (GVHD) is due to inadequate thymic function by examining pretransplant serum levels of facteur thymique serique (FTS). Four of five patients with no detectable FTS activity developed chronic GVHD, while one of four with some FTS activity did. Further patient numbers are needed to confirm or reject this hypothesis. We further postulated that chronic GVHD, whatever its cause, involves thymic epithelium as a target organ. When tested 11 mo or more posttransplant, patients with chronic GVHD had lower absolute FTS levels (p less than 0.02) and lower age-corrected levels (p = 0.05) than patients without chronic GHVD. Low values in chronic GVHD were associated with the disease itself and not its therapy. These findings show that thymic epithelial secretory function is impaired in chronic GVHD, and this may in part be responsible for the immunodeficiency characteristic of these patients.
Cyclosporin-A is selectively cytotoxic to human leukemic T cells in vitro
Authors: Totterman TH , Danersund A , Nilsson K , Killander A 
Published: October 2019

Abstract
We have studied the antileukemic effects of cyclosporin-A (CyA) on the cells of a number of human hematopoietic biopsies and established cell lines in vitro. Cya killed the tumor cells but not the nonmalignant control cells from three of four patients with T-lymphocytic leukemia/lymphoma at concentrations comparable to those recommended in clinical long-term immunosuppressive therapy. The leukemic cells from 7 patients with B-type chronic lymphocytic leukemia were insensitive to CyA. The drug was cytostatic and cytolytic to three of five T- lymphoblastic leukemia cell lines tested. With the possible exception of a plasma cell line, all other control cell lines (B-lymphocytic lymphoma, histiocytic lymphoma, fibroblast, and glia cell lines) were resistant to CyA. These observations indicate that CyA or its derivatives may be useful as a highly selective antitumor agent in different T-cell malignancies.
Hereditary high concentration of glutathione in canine erythrocytes associated with high accumulation of glutamate, glutamine, and aspartate
Authors: Maede Y , Kasai N , Taniguchi N 
Published: October 2019

Abstract
We have found a dog family in which there were five cases of increased red cell glutathione corresponding to four to five times the normal concentration without any clinical signs. In the present study, we mainly examined the concentrations of free amino acids in the erythrocytes, plasma, and urine of two of the dogs, and we demonstrated that the concentrations of glutamate, aspartate, and glutamine in their erythrocytes increases to 92, 63, and 13 times the mean value in the normal blood, respectively. There were no changes observed in the other amino acids as compared to normal, although the glycine and histidine in the erythrocyte showed slight increases. The concentrations of amino acids in the plasma and urine of the dogs were almost equal to normal ones. The activities of some of the enzymes involved in the glutathione metabolism in the erythrocytes from the two dogs were all within the normal range. The increased level of glutathione could be explained by the fact that the feedback inhibition of gamma-glutamyl cysteine synthetase by glutathione was released by the high levels of glutamate in the erythrocytes.
Pipobroman therapy of polycythemia vera
Authors: Najman A , Stachowiak J , Parlier Y , Gorin NC , Duhamel G 
Published: October 2019

Abstract
Between 1971 and 1981, 74 patients with polycythemia vera were treated with pipobroman using a high-dose induction, low-dose maintenance regimen. Complete remission was achieved in 51 of 54 previously untreated patients (94.4%) and in 17 of 20 patients (85%) previously treated wih radioactive phosphorus (32 p) and busulfan. The earliest modifications were noted on day 16, and on the average, blood counts were normal by day 45. Thirty percent of the patients relapsed, the mean duration of the remission being 17.5 mo. Following recurrence pipobroman was consistently effective in the same doses but the mean duration of the next remissions was 10 mo. Transient leukopenia and thrombocytopenia occurred in 8% and 7% of patients, respectively, during initial phase, and anemia was noted in 3 patients. Macrocytosis was noted in 20% of patients during maintenance phase. Three cases of acute leukemia and 3 cases of osteomyelosclerosis were recorded, all occurring in patients who had previously received 32 p and/or busulfan. No hematologic malignancies were seen among patients treated with pipobroman alone; follow-up exceeded 6 yr for 20 patients and the median follow-up period was 3.6 yr. Pipobroman appears safer than other alkylating agents; it is as effective as 32 p and works more quickly. Longer follow-up will be required to evaluate the drug's oncogenic potential, which is still not known.
The effect of pharmacologic inhibition of phospholipid methylation on human platelet function
Authors: Shattil SJ , Montgomery JA , Chiang PK 
Published: October 2019

Abstract
Human platelets are capable of synthesizing their major membrane phospholipid, phosphatidylcholine, by a methylation pathway. This involves the sequential transfer of methyl groups from S-adenosyl-L- methionine (AdoMet) to phosphatidylethanolamine, and in the process, AdoMet is converted to S-adenosylhomocysteine (AdoHcy). The activity of this methylation pathway is decreased upon stimulation of platelets by various agonists. We inhibited methylation reactions pharmacologically to see whether this inhibition plays any role in the process of platelet activation. Two inhibitors of AdoHcy hydrolase, 3-deaza- adenosine and 3-deaza-(+/-)aristeromycin (500 microM each), were effective in increasing platelets levels of AdoHcy and preventing turnover of AdoMet. Also, these compounds were equipotent in inhibiting platelet phospholipid methylation. However, while 3-deaza-adenosine potentiated platelet aggregation and 14C-serotonin release induced by epinephrine or adenosine diphosphate (ADP) (p less than 0.01), 3-deaza- aristeromycin had no such effect. Neither compound affected platelet responses to thrombin or collagen. Inhibition of methylation reactions was not the only biochemical effect of 3-deaza-adenosine since it also blunted significantly the elevation of platelet cyclic adenosine monophosphate (AMP) levels induced by prostaglandin E1 (p less than 0.02). Therefore, these studies demonstrate that inhibition of platelet phospholipid methylation, per se, has no discernable effect on the function of human platelets. The methylation pathway, though active in platelets, does not appear to be primarily involved in membrane events responsible for platelet activation.
The immunologic phenotyping of bone marrow biopsies and aspirates: frozen section techniques
Authors: Wood GS , Warnke RA 
Published: October 2019

Abstract
Techniques were developed for the preparation of frozen sections from undecalcified bone marrow biopsy cores and bone marrow aspirates. Selected indirect antibody and biotin-avidin detection systems, employing immunoperoxidase or immunofluorescent labels, were studied to determine which were best suited for bone marrow frozen section immunohistopathology. Methods employing murine hybridoma monoclonal antibodies illustrate the immunophenotyping of representative lymphoid neoplasms, involving bone marrow. The results of immunohistologic staining were comparable to those of fluorescence-activated cell sorter (FACS) analysis of cell suspensions. The advantages and limitations of immunohistologic techniques are discussed as they relate to immunophenotypic studies previously feasible only with bone marrow cell suspensions. Frozen section immunohistologic techniques serve as useful adjuncts to the conventional evaluation of bone marrow aspirates and biopsies.
Survival in Hodgkin's disease: the role of immunocompetence and other major risk factors
Authors: Faguet GB , Davis HC 
Published: October 2019

Abstract
The prognostic value of age, sex, symptoms, histopathology, lymphocyte count, skin tests, immunocompetence (lymphocyte response profile to a spectrum of PHA concentrations), and stage was evaluated in 35 previously untreated patients with Hodgkin's disease by multiple linear regression and logistic analysis. Immunocompetence exhibited the highest correlation (R = 0.537) with survival status and was required as a common denominator for deriving best sets of two or more variables. In addition, immunocompetence contributed to all other variables combined (p = 0.023), whereas stage did not (p = 0.116). Immunocompetence, age, symptoms, and histopathology generated a highly discriminant (R = 0.784) model not improved by stage or by other variables (p greater than or equal to 0.159). The utility and generalizability of this model are shown by a correct classification of 91.2% of cases according to expected versus actual survival status and by a predicted correlation (R) of 0.71, respectively, neither improved by sex, lymphocyte count, skin tests, or stage. In comparison, the conventional triad of stage, symptoms, and histopathology correctly classified only 70.6% of cases and showed actual and predicted correlations with survival status of R = 0.550 and R = 0.51. We conclude that immunocompetence is a powerful discriminant risk factor in Hodgkin's disease that exerts a pivotal role on survival and serves as a basis for models of greater discriminant power and generalizability than the conventional stage-based evaluation triad. Immunocompetence-based models are expected to provide a more discriminating basis for clinical evaluation, prediction of prognosis, and treatment selection for patients with Hodgkin's disease.
The use of the synthetic peptide, Gly-Pro-Arg-Pro, in the preparation of thrombin-degranulated rabbit platelets
Authors: Harfenist EJ , Guccione MA , Packham MA , Mustard JF 
Published: October 2019

Abstract
The method for preparing thrombin-degranulated platelets has been modified to avoid the use of plasmin or successive treatments with small amounts of thrombin, while still achieving more than 90% release of platelet amine storage granule contents. It was necessary to prevent the fibrinogen released from the platelets during thrombin treatment from forming an insoluble fibrin mesh that could trap the platelets and hinder their deaggregation. To accomplish this we have treated rabbit platelets with 0.73 U/ml of thrombin for 1 min in the presence of the synthetic peptide, Gly-Pro-Arg-Pro, which prevents the polymerization of fibrin molecules. We have demonstrated that it also prevents 125I, initially added as 125I-fibrinogen, from associating with the platelets in a form that was not removed by centrifuging and washing during the preparation of thrombin-degranulated platelets, and we infer that products formed from the fibrinogen released from the platelets would also be prevented from associating with them. Thrombin-degranulated platelets prepared by this method have lost 92% of their granule contents and they can be washed and resuspended. These platelets aggregate normally upon stimulation with thrombin, adenosine diphosphate (ADP), or arachidonate. Thus, Gly-Pro-Arg-Pro is useful in preparing thrombin-degranulated platelets for studying platelet reactions without the complicating effects of released materials such a ADP and fibrinogen.