bluuebunny/crossref_metadata_2025_split huggingface dataset:
Presenting features and prognosis of chronic lymphocytic leukemia in younger adults [see comments]
Authors: Montserrat E , Gomis F , Vallespi T , Rios A , Romero A , Soler J , Alcala A , Morey M , Ferran C , Diaz-Mediavilla J 
Published: October 2019

Abstract
We have analyzed 117 younger patients with chronic lymphocytic leukemia (CLL) (mean age, 44.5 years; SD, 4.8; range, 19 to 49; male/female ratio, 2.08) with three main objectives: (1) to see whether these patients have distinctive presenting clinical features; (2) to investigate the impact of the disease on survival; and (3) to analyze whether already well-known prognostic factors are also useful when applied to these patients. As compared with an older age population (greater than or equal to 50 years), there were no major differences in presenting features except for an increased proportion of males (2.08 v 1.21; P less than .025) and a higher hemoglobin level (13.47 +/- 2.70 g/dL v 12.84 +/- 2.77 g/dL; P less than .05) in the younger group. Median survival is 12.3 years (expected median from a control group, 31.2 years). Clinical stages, bone marrow patterns, blood lymphocyte counts, and its doubling time are all useful to separate different risk groups of patients. Whereas patients with favorable prognostic factors have a survival probability of about 80% 14 years after diagnosis, those with poor prognostic features have a median survival of less than 3 years. It is concluded that CLL in younger adults has no major distinctive presenting features and that known prognostic factors are useful to separate different risk groups of patients. These results should be of help in planning therapy for younger persons with CLL.
Ig VH gene expression among human follicular lymphomas
Authors: Bahler DW , Campbell MJ , Hart S , Miller RA , Levy S , Levy R 
Published: October 2019

Abstract
Thirty-six randomly selected cases of low grade follicular lymphoma (FL) were analyzed for Ig heavy chain variable region (VH) gene expression. Assignment to one of the six human VH gene families (VH1 to VH6) was made with a polymerase chain reaction-based technique using family-specific leader primers. The frequency of VH family use in FL was found to be similar to that reported for normal peripheral blood lymphocytes and is therefore also roughly proportional to VH family size. To evaluate expression within an individual family, all of the lymphoma VH genes from the middle size VH4 family were sequenced and compared with previously published sequences. Of these eight lymphoma VH sequences, six were most closely related to just two of the 10 known functional VH4 germline genes. Nonrandom usage by FL of the JH3, JH4, and JH5 joining segments was also observed. Nucleotide sequences were also determined for 10 randomly selected lymphoma VH genes from the large VH3 family. With one possible exception, none of these lymphoma VH sequences appear to represent any of the VH3 genes that may be preferentially used in the fetal repertoire.
Inhibitory effect of interleukin-4 on the in vitro growth of Ph1- positive acute lymphoblastic leukemia cells
Authors: Okabe M , Kuni-eda Y , Sugiwura T , Tanaka M , Miyagishima T , Saiki I , Minagawa T , Kurosawa M , Itaya T , Miyazaki T 
Published: October 2019

Abstract
We investigated the effect of recombinant human interleukin-4 (rhIL-4) on the in vitro growth of human leukemia cells in liquid culture and 3H- thymidine incorporation and found inhibitory effects on the growth of leukemic cells from patients with Ph1-positive acute lymphoblastic leukemia (Ph1 ALL) and three Ph1 ALL cell lines. However, no inhibitory effects were seen in Ph1-positive leukemic cell lines derived from patients with chronic myelogenous leukemia in blast crisis and various types of Ph1-negative leukemia cells, including B-lineage leukemia cells. In a flow cytometry assay of IL-4 receptor (IL-4R), all three Ph1-positive ALL cell lines showed the presence of IL-4R on their cell surfaces, and the IL-4-dependent inhibition on the growth of Ph1- positive ALL cells was abrogated by the addition of either monoclonal or polyclonal antibodies against rhIL-4. Other cytokines, including IL- 2, IL-3, granulocyte-macrophage colony-stimulating factor (CSF), granulocyte-CSF, and IL-6, showed no inhibitory effects on the growth of Ph1-ALL cells, but tumor necrosis factor-alpha (TNF-alpha) and interferon (IFN)-alpha, -beta, and -gamma displayed slight inhibitory effects in a high concentration. The growth inhibition induced by rhIL- 4 in the Ph1-positive ALL cells was not abrogated by the addition of antibodies against either IFN-gamma or TNF-alpha. Furthermore, these cells showed no significant production of IFN-alpha, -beta, or -gamma or TNF-alpha after exposure to rhIL-4, thus indicating that the growth inhibition of Ph1-positive ALL cells by rhIL-4 is not associated with IL-4-stimulating production of these factors. rhIL-4 caused significant inhibition of the tyrosine kinase activity in these Ph1-positive ALL cells, similar to Herbimycin A, an inhibitor of tyrosine kinase that inhibited the tyrosine kinase activity in these cells. Our finding suggests that the clinical evaluation of rhIL-4 may offer promising therapeutic possibilities for patients with Ph1-positive ALL.
Improvement of mouse beta-thalassemia by recombinant human erythropoietin
Authors: Leroy-Viard K , Rouyer-Fessard P , Beuzard Y 
Published: October 2019

Abstract
Homozygous beta thalassemic mice received 50 U (1,660 U/kg) of recombinant human erythropoietin (rhEpo) 5 days a week for 2 weeks. Hemoglobin increased from 9.2 +/- 0.6 g/dL to 10.5 +/- 0.4 g/dL (P = .002) and hematocrit increased from 29.2% +/- 0.9% to 34.1% +/- 1.9% (P = .0014). The beta minor/alpha globin chain synthesis ratio increased slightly but significantly between day -4 (0.75 +/- 0.07) and day 4 (0.81 +/- 0.04) (P = .01) and reached a minimum ratio (0.67 +/- 0.03) on day 15 (P = .001), being parallel to reticulocyte counts and to the incorporated trichloracetic acid (TCA)-insoluble radioactivity, therefore parallel to the erythropoietic output in thalassemic mice, as in normal mice. Erythrocyte defects were improved in beta thalassemic mice treated by rhEpo: membrane-associated alpha globin was significantly decreased (P less than .01), thiol group reactivity of ankyrin was significantly improved (P less than .05), spectrin alterations were reduced, and deformability of mouse thalassemic red blood cells was normalized. These results provide experimental criteria for modulating globin chain imbalance necessary for the therapy of human beta thalassemia intermedia, and suggest that rhEpo might be of interest to improve the red blood cell mass and reduce erythrocyte alterations in this disease.
Treatment type and amount influenced human immunodeficiency virus seroprevalence of patients with congenital bleeding disorders
Authors: Gjerset GF , Clements MJ , Counts RB , Halvorsen AS , Thompson AR 
Published: October 2019

Abstract
Two hundred and eighty-two patients with congenital bleeding disorders received blood component replacement therapy between January 1979 and April 1985, were followed-up by the Puget Sound Blood Center's Hemophilia Care Program, and were tested for antibody to human immunodeficiency virus (HIV). Serologic results were obtained at least 1 year after the last exposure to volunteer donor products that were prepared before donor HIV screening or after the last exposure to concentrates produced before the manufacturer's use of treatment methods for inactivation of HIV. In all, 106 patients were anti-HIV positive. The risk of HIV infection was greater in patients with more severe bleeding tendencies, greater exposure to components, and exposure to lyophilized concentrates from large pools of donors. Of 100 patients with hemophilia A who only received cryoprecipitate from volunteer donors from Washington State (during the 6.3-year period), 14% had become anti-HIV positive. Of 27 patients receiving mostly cryoprecipitate but also being exposed to a single lot of concentrate during the same period, 13 (48%) were positive. Of 49 patients treated predominantly or solely with factor VIII concentrates during this period, 43 (88%) were anti-HIV positive. Of 29 patients with von Willebrand disease, four were anti-HIV positive, including 2 of 26 receiving only cryoprecipitate and two of three who had received a single dose of factor VIII concentrate. Of 19 patients who were treated solely with volunteer donor plasma, all remained anti-HIV negative. Of 47 patients exposed to factor IX concentrate, 28 (60%) were positive. Data relevant to the risk of HIV transmission subsequent to screening of the volunteer donor population were also obtained. Treatment records of 55 hemophilia A patients who have remained anti-HIV negative through at least June 1990 showed exposure to 71,173 screened donors from May 1985 through December 1989, and all 55 patients have remained anti-HIV negative.
A randomized controlled trial of recombinant interferon-alpha in chronic hepatitis C in hemophiliacs
Authors: Makris M , Preston FE , Triger DR , Underwood JC , Westlake L , Adelman MI 
Published: October 2019

Abstract
Chronic liver disease associated with hepatitis C virus (HCV) is an important cause of morbidity and mortality in hemophilia. We have used recombinant interferon alpha-2b (IFN alpha-2b) in a randomized controlled liver biopsy trial to treat hemophiliacs with chronic hepatitis. Eighteen patients entered the study, 16 of whom were subsequently shown to have antibodies to the HCV. All underwent liver biopsy at entry and were randomized to either treatment with self- administered IFN alpha-2b, 3 million units subcutaneously thrice weekly (n = 10) or no treatment (control group) (n = 8). Nine subjects had chronic active hepatitis, seven had chronic persistent hepatitis, and two had cirrhosis. Twelve months after entry into the study 17 patients underwent a second liver biopsy. All biopsies were coded, assessed, and scored according to the histologic severity of the liver disease. Ten patients were administered IFN for 1 year, and in four patients normalization of alanine aminotransferase (ALT) occurred compared with none in the untreated group. After the second liver biopsy, six of the eight initial no-treatment patients were treated with interferon 3 million units thrice weekly for 6 months, and normalization of ALT was seen in five patients. Biochemical relapse within 4 months of stopping IFN occurred in one of four patients treated for 1 year and in four of five patients treated for 6 months. IFN treatment was well tolerated. Although the histologic scores of the two groups were similar at entry into the study, after 12 months the biopsy appearances in the treated group were significantly improved compared with the controls (P less than .01). Histologic improvement was noted in the three interferon- treated human immunodeficiency virus antibody-positive patients and also in other patients who had no biochemical response. We conclude that low-dose recombinant IFN alpha is effective in normalizing transaminases and improving the histologic appearances in at least 50% of hemophiliacs with chronic hepatitis C.
Fibrinogen Ledyard (A alpha Arg16----Cys): biochemical and physiologic characterization
Authors: Lee MH , Kaczmarek E , Chin DT , Oda A , McIntosh S , Bauer KA , Clyne LP , McDonagh J 
Published: October 2019

Abstract
Fibrinogen Ledyard was discovered in a 10-year-old boy with a mild bleeding history. His father had the same defect and a bleeding history after surgery. Both patients were heterozygous. The plasma fibrinogen concentration was normal immunologically (335 mg/dL) and very low functionally (52 mg/dL). Purified fibrinogen Ledyard had a prolonged polymerization, which was somewhat corrected by addition of Ca2+ ions. High performance liquid chromatography (HPLC) analyses of the fibrinopeptides released by thrombin showed 1 mol of fibrinopeptide A (FPA) and 2 mol of fibrinopeptide B (FPB) released per mole of fibrinogen Ledyard. Steady-state kinetic parameters were evaluated for release of FPA by thrombin. When the concentration of fibrinogen Ledyard was corrected to 50% of total protein, because only 50% of fibrinogen Ledyard can release FPA, the kinetic constants were similar to those of control fibrinogen (Km = 7.5 mumol/L for A alpha chain, kcat = 54 s-1). This finding indicates that the cleavage site of the A alpha chain in these abnormal molecules may not interact with the catalytic site of thrombin. The three chains of fibrinogen Ledyard were isolated on reverse-phase C4-HPLC. The sequence of the amino terminus of A alpha chain showed that Arg in position 16 was replaced by Cys in the abnormal molecules. Approximately half of fibrinogen Ledyard (52%) was clotted by reptilase, suggesting that fibrinogen Ledyard may consist of 50% normal homodimers (A alpha Arg16 . A alpha Arg16) and 50% abnormal homodimers (A alpha Cys16 . A alpha Cys16). Abnormal molecules could form disulfide bond between the A alpha Cys16 residues. Thus, the abnormal molecules have a different structure that does not bind to thrombin. Probably the abnormality of polymerization of fibrinogen Ledyard results from the interaction of the abnormal molecules with normal fibrin monomers, so that the growth of fibrin protofibrils is inhibited. This abnormal fibrinogen supports adenosine diphosphate-induced platelet aggregation in a normal manner.
Establishment of an interleukin-3-dependent leukemic cell line from a patient with chronic lymphocytic leukemia in the acute phase
Authors: Tohda S , Nara N , Murohashi I , Aoki N 
Published: October 2019

Abstract
A novel human leukemic cell line, TMD2, which proliferates dependently on interleukin-3 (IL-3), was established from the peripheral blood (PB) of a patient with chronic lymphocytic leukemia (CLL) in the acute phase. After 8 years of the chronic phase of CLL, lymphoblastoid cells appeared and became dominant in the PB. After repeated subcultures of the patient's PB cells in the acute phase, lymphoblastoid cells have proliferated actively in the presence of recombinant human IL-3, and the TMD2 cell line has been established. The lymphoblastoid cells in acute phase and TMD2 cells proliferated dependently on IL-3, whereas growth of the small lymphocytes in chronic phase was not supported by IL-3. Other ILs (IL-1, 2, and 4 through 6) or CSF did not support the growth or survival of TMD2 cells. The existence of high-affinity receptors for IL-3 was shown on TMD2 cells (binding sites 88 per cell, Kd = 76.9 pmol/L). DNA extracted from the small lymphocytes in the chronic phase, the lymphoblastoid cells in the acute phase, and TMD2 cells showed the same rearrangement pattern of the immunoglobulin heavy- chain gene. Therefore, these cells were considered to have originated from the same clone. These results imply that a genetic event that caused the responsiveness to IL-3 in the cell of the chronic phase caused the acute transformation of CLL in this patient. We consider that TMD2 cell line is valuable as a model of cells of CLL in the acute phase and as a tool for studying the signal transduction system of IL-3.
CD10 (CALLA)/neutral endopeptidase 24.11 modulates inflammatory peptide- induced changes in neutrophil morphology, migration, and adhesion proteins and is itself regulated by neutrophil activation
Authors: Shipp MA , Stefano GB , Switzer SN , Griffin JD , Reinherz EL 
Published: October 2019

Abstract
The common acute lymphoblastic leukemia antigen (CALLA, CD10), which is expressed on early lymphoid progenitors and neutrophils, is the zinc metalloprotease, neutral endopeptidase 24.11 (NEP, “enkephalinase”). The CD10 cell surface enzyme is known to hydrolyze a variety of biologically active peptides including met-enkephalin, formyl-met-leu- phe (f-MLP), and substance P. These three CD10/NEP substrates induce the migration and aggregation of neutrophils, suggesting that each of the peptides can function as a mediator of neutrophil inflammatory responses. Recently, inhibition of CD10/NEP was found to reduce the concentration of metenkephalin needed to activate human and invertebrate granulocytes by several orders of magnitude. Herein we show that f-MLP and substance P induce rapid changes in neutrophil morphology, migration, and adhesion molecule expression, including upregulation of Mo1 (CD11b/CD18) and shedding of LAM-1 (also known as LECAM-1, Leu8, or TQ-1, the human homologue of murine gp100MEL14). Importantly, these coordinated changes are potentiated by inhibition of cell surface CD10/NEP enzymatic activity. Neutrophil cell surface CD10/NEP enzymatic activity is also shown to be regulated by the activation state of the cell during the time period in which the enzyme has its most pronounced effects. These results suggest that in neutrophils, CD10/NEP functions to control responsiveness to multiple inflammatory peptides.
Antivinculin antibodies in sera of patients with immune thrombocytopenia and in sera of normal subjects
Authors: Tomiyama Y , Kekomaki R , McFarland J , Kunicki TJ 
Published: October 2019

Abstract
We have characterized a 120-Kd antigen that frequently reacts with serum antibodies from patients with immune thrombocytopenia or normal subjects. Immunoblots made after two-dimensional nonreduced/reduced sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) or two-dimensional isoelectric focusing/SDS-PAGE demonstrated that this 120-Kd protein has the same molecular weight under nonreduced or reduced conditions, is not a surface protein, and has an isoelectric point (pl) of 6.4 to 6.5. From these data, one likely candidate is the intracellular platelet protein, vinculin. Monoclonal antivinculin antibody reacts with this 120-Kd protein, and purified human platelet vinculin is bound by antibodies that recognize the 120-Kd protein. Therefore, we conclude that this 120-Kd protein is identical to vinculin. Data obtained from a sensitive enzyme-linked immunosorbent assay demonstrate the presence of naturally occurring antivinculin antibodies in many normal sera. However, the incidence of antivinculin antibodies in patient sera (67%; 55 of 82 sera) is significantly (P less than .01) higher than that in normal sera (40%; 32 of 80 sera), and there is a significant difference (P less than .05) between the mean levels of antivinculin antibodies in patient and normal sera. Whereas the levels of these antibodies in patient and normal sera overlap, 2 of 82 sera from patients with thrombocytopenia express unusually high levels of such antibodies. The pathologic significance of these antibodies remains to be determined.
Translocations involving band 3q27 and Ig gene regions in non-Hodgkin's lymphoma [see comments]
Authors: Bastard C , Tilly H , Lenormand B , Bigorgne C , Boulet D , Kunlin A , Monconduit M , Piguet H 
Published: October 2019

Abstract
We report a series of 20 non-Hodgkin's lymphomas (NHL) in which cytogenetic analysis showed a translocation involving band 3q27 and the site of one of the three Ig genes (14q32, 2p12, 22q11) in the neoplastic cells. These cases were found in a series of 319 patients with clonal chromosomal abnormalities studied over a 7-year period. Fourteen patients had diffuse lymphoma, mainly of large cell type and the remaining six were follicular lymphomas. All cases studied were of B-cell phenotype. A t(3;14)(q27;q32) was commonest, found in 15 patients (4.7%), with the two variant translocations, t(3;22)(q27;q11) and t(2;3)(p12;q27), being found in three and two patients, respectively. Additional chromosomal defects were present in most patients, but two patients had this type of translocation as the sole abnormality. These results indicate that translocations involving band 3q27 and Ig genes are not uncommon, and suggest that a novel oncogene, located at band 3q27, may be implicated in B-cell NHL.
Multicenter randomized study comparing cyclosporine-A alone and antithymocyte globulin with prednisone for treatment of severe aplastic anemia
Authors: Gluckman E , Esperou-Bourdeau H , Baruchel A , Boogaerts M , Briere J , Donadio D , Leverger G , Leporrier M , Reiffers J , Janvier M 
Published: October 2019

Abstract
We report the results of a randomized multicenter study comparing the efficacy of antithymocyte globulin (ATG) with that of cyclosporin A (CsA) as first-line therapy for severe aplastic anemia (SAA). Patients were randomized to receive ATG and prednisone (PDN) or CsA; hematologic response and toxicity were compared. At 3-month evaluation, patients who had no or minimal response received the alternative therapy to assess the value of a sequential immunosuppressive therapy for treatment of severe aplastic anemia. One hundred nineteen patients were randomized; 25 were excluded, of whom 3 were misdiagnosed and 22 did not follow the cross-over protocol. Ninety-four patients were analyzed; 46 received CsA, and 48 received ATG-PDN. The actuarial survival was 66.7%, with a median follow-up time of 19 months. There was no significant difference in survival between the groups with, at 3 months, an actuarial survival of 88% in the CsA group and 75% in the ATG group (NS); at 12 months, it was 70% in the CsA group and 64% in the ATG group (NS). The percentage of complete and partial response was 11.6% and 16%, respectively, at 3 months, and 31.6% and 30%, respectively, at 12 months (NS). The main prognostic factor was the absolute neutrophil count (ANC) at entry: Patients with ANC less than 0.2 x 10(9)/L had a significantly lower survival as compared with patients with more than 0.2 x 10(9)/L ANC (P = .0001). At 12 months, 62 evaluable patients were alive, with a complete or partial response in 36 patients. Patients who had responded to the first treatment had a better recovery of bone marrow failure than those who had sequential immunosuppression. The main complication was infection, which was more often observed and more often lethal during ATG and PDN therapy. In this study, initial treatment of SAA with either CsA or ATG-PDN followed by cross-over therapy for nonresponders produced comparable response and survival rates.
Macrophage-inflammatory protein protects multipotent hematopoietic cells from the cytotoxic effects of hydroxyurea in vivo
Authors: Lord BI , Dexter TM , Clements JM , Hunter MA , Gearing AJ 
Published: October 2019

Abstract
Macrophage inflammatory protein-1 alpha (MIP-1 alpha) has been assessed for its potential in vivo to protect hematopoietic progenitor cells from the cytotoxic effects of a cycle-specific drug--in this case hydroxyurea (HU). Two doses of HU, 7 hours apart, were administered to mice to induce spleen colony-forming unit (CFU-S) cycling and then to kill them during DNA-synthesis. MIP-1 alpha, in a variety of dose and time combinations, was injected before the second dose of HU in an attempt to prevent recruitment or maintain CFU-S quiescence, and thus protect them from the second dose of HU. Without MIP-1 alpha, recovery of the CFU-S population was complete in 7 days. In a dose-dependent manner, MIP-1 alpha either reduced the initial kill and accelerated recovery, or completely protected the CFU-S population. We conclude that MIP-1 alpha does protect multipotent progenitor cells in vivo and that these observations provide a base from which to build practical clinical applications.