bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sustained thrombolysis with DNA-recombinant tissue type plasminogen activator in rabbits
Authors: Agnelli G , Buchanan MR , Fernandez F , Van Ryn J , Hirsh J 
Published: October 2019

Abstract
Tissue type plasminogen activator (t-PA) is an effective thrombolytic agent in experimental animals. The duration of the thrombolytic effect of infused t-PA is unknown. We compared the duration of the thrombolytic effect of t-PA with streptokinase by measuring the lysis of 125I-fibrin-labeled thrombi in rabbit jugular veins at different times after a bolus injection of the fibrinolytic agents. The pharmacodynamics of both thrombolytic agents were determined in rabbits using a sensitive ex vivo fibrinolytic assay. Streptokinase and t-PA were given as a bolus dose of 15,000 U/kg. There was no detectable circulating fibrinolytic activity 30 minutes after the bolus dose of t- PA and 120 minutes after the bolus dose of streptokinase. The t-PA injection produced 34% thrombolysis at 30 minutes, 90% thrombolysis at 120 minutes, and 96% thrombolysis at 240 minutes. The streptokinase injection produced 17% thrombolysis at 30 minutes, 34% at 120 minutes, and 34% at 240 minutes. These observations indicate that the thrombolytic effect of t-PA is sustained beyond its time of clearance from the circulation whereas the thrombolytic effect of streptokinase closely parallels its activity in the circulation.
Autologous bone marrow transplantation for patients with acute lymphoblastic leukemia in second or subsequent remission: results of bone marrow treated with monoclonal antibodies BA-1, BA-2, and BA-3 plus complement
Authors: Ramsay N , LeBien T , Nesbit M , McGlave P , Weisdorf D , Kenyon P , Hurd D , Goldman A , Kim T , Kersey J 
Published: October 2019

Abstract
Autologous bone marrow transplantation (BMT) was utilized as therapy for 23 patients with acute lymphoblastic leukemia (ALL) in second or greater remission. Bone marrow was treated in vitro with a combination of monoclonal antibodies, consisting of BA-1, BA-2, BA-3, and baby rabbit complement (BRC'). All patients were prepared for transplantation with cyclophosphamide and fractionated total body irradiation. Engraftment occurred in all 23 patients. Seven of 23 patients remain relapse-free from six to 32 months (median, 21.4 months) posttransplant. Failures were due to relapse with the exception of one patient who died of infection. This study demonstrates that autologous BMT using in vitro marrow treatment with BA-1, BA-2, BA-3, and BRC' is safe, allows engraftment, and results in prolonged survival for some patients with ALL in second or greater remission.
5-Azacytidine increases HbF production and reduces anemia in sickle cell disease: dose-response analysis of subcutaneous and oral dosage regimens
Authors: Dover GJ , Charache S , Boyer SH , Vogelsang G , Moyer M 
Published: October 2019

Abstract
Varying doses of 5-azacytidine (5-aza) were given to four sickle cell individuals for 500, 200, 100, and 30 days. The percentage of fetal hemoglobin (HbF) containing reticulocytes (F reticulocytes) increased two- to five-fold within five days of 5-aza therapy in all patients, with a two- to three-fold rapid response (less than 48 hours after initial dose) in three patients. Reticulocyte suppression was not observed prior to, during, or after therapy in those patients who responded within 48 hours. Subcutaneous 5-aza was given in 35-day courses consisting of every day, every other day, or three consecutive days a week. No marrow toxicity was observed on any of the regimens. For three patients, the highest average F reticulocyte level was observed on the three consecutive day a week regimen. Oral 5-aza, given with tetrahydrouridine, produced comparable F reticulocyte response. In the two patients treated for more than 100 days, Hb levels increased to 11 to 12 and 9 g/dL, MCV and MCH increased by 25%, and lysate HbF levels peaked at 12% and 20%. Fetal erythroid characteristics (i- antigen, galactokinase activity, and G gamma/A gamma ratios) did not correlate with maximal HbF production. The frequency of vasoocclusive crises appeared to decrease in both patients followed for more than 100 days.
Hypoplastic anemia in B cell chronic lymphocytic leukemia: evolution of T cell-mediated suppression of erythropoiesis in early-stage and late- stage disease
Authors: Mangan KF , D'Alessandro L 
Published: October 2019

Abstract
To define further the role of marrow T suppressor lymphocytes in the pathogenesis of the hypoproliferative anemia in all Rai clinical stages of B cell chronic lymphocytic leukemia (CLL), marrow erythroid progenitor cell (CFU-E and BFU-E) frequency, marrow T gamma lymphocyte frequency per 1,000 nucleated marrow cells, and T cell-erythroid progenitor cell interactions were examined in 30 CLL patients and normal control subjects. As compared with control subjects, decreased numbers of CFU-E and BFU-E were found in patient marrow depleted of neoplastic B cells in all Rai stages of the disease. As a group, Rai stage III through IV patients with or without aplasia (CLL-aplasia) had significantly fewer CFU-E and BFU-E than did Rai O through II stage patients. The numbers of T gamma cells infiltrating CLL marrows were increased 3, 9, and 20 times normal in Rai O through II, Rai III through IV, and CLL-aplasia groups, respectively. Removal of T cells from marrow increased growth of CFU-E and BFU-E in all Rai O through IV patients, but the increase was significant in the CLL-aplasia group only (P less than .05). However, autologous coculture of marrow T cells or T gamma cells but not B cells with marrow B + T-depleted null cells at ratios of 0.2:1 to 1:1 suppressed CFU-E and BFU-E growth in all three patient groups. We conclude that the hypoproliferative anemia occurring in the course of B cell CLL is due to gradual accumulation in the marrow of T gamma lymphocytes which suppress erythroid progenitor cell growth. T gamma cell suppression of erythropoiesis and marrow T gamma cell expansion is detectable in the earliest Rai stages of the disease.
Role of immune interferon in the monocytic differentiation of human promyelocytic cell lines induced by leukocyte conditioned medium
Authors: Dayton ET , Matsumoto-Kobayashi M , Perussia B , Trinchieri G 
Published: October 2019

Abstract
Conditioned medium (CM) from lectin-stimulated human leukocytes contains factors that induce human promyelocytic cell lines to differentiate along the monocytic pathway. In this report, we show that human promyelocytic cell lines are also induced to differentiate along this pathway by immune interferon (IFN gamma). Various preparations of IFN alpha tested did not induce this differentiation. In cultures containing IFN gamma, the cells are induced to coordinately express monocyte markers and functions such as monocyte-specific surface antigens, HLA-DR antigens, nonspecific esterase, receptors for the Fc fragment of IgG, and the ability to mediate antibody-dependent cell- mediated cytotoxicity. Our data indicate that differentiation induced by IFN gamma is not secondary to an arrest of growth of promyelocytic cell lines, but rather that a proportion of cells is induced along a programmed pathway of terminal differentiation similar to that of normal monocytes. CM contains IFN gamma, but its ability to induce differentiation is greater than expected on the basis of its content of IFN gamma. Treatments at 56 degrees C or at pH 2.0, which abolish IFN gamma activity, abrogate the differentiation ability of CM. The antiviral activity and the differentiation activity contained in the CM are coeluted from gel filtration and reverse-phase columns. Monoclonal antibodies anti-IFN gamma, which completely abrogate the differentiation ability of IFN gamma and the antiviral activity in the CM, completely suppress the induction of some monocyte markers by CM, but only reduce the expression of others. When IFN gamma is added to CM, promyelocytic cell lines are induced to differentiate to a much greater extent than that induced by either IFN gamma or IFN gamma- depleted CM alone. These results show that the differentiation activity of leukocyte CM is due to the synergistic effect of IFN gamma and other factors not yet identified.
Surface membrane glycoproteins of wild-type and differentiation-inducer- resistant HL-60 cells
Authors: Felsted RL , Gupta SK , Glover CJ , Gallagher RE 
Published: October 2019

Abstract
Surface membrane glycoproteins (SMGs) of cells from the parental wild- type HL-60 cell line and from three sublines variably cross-resistant to the granulocyte differentiation-inducing effects of retinoic acid (RA), dimethylsulfoxide (DMSO), and certain purine bases (6-thioguanine [6TG] or hypoxanthine) were studied by one-dimensional and two- dimensional gel electrophoresis. After both oligosaccharide (periodate/borotritide) and peptide (1,3,4,6-tetrachloro-3 alpha, 6 alpha-diphenylglycouril) ectolabeling procedures, striking common changes were noted in the gel electrophoretic patterns of the SMGs from the RA- and 6TG-resistant sublines compared to those from the wild-type HL-60 line or the DMSO-resistant subline. Most prominently, this included the presence in the RA- and 6TG-resistant cells of an apparent high molecular weight acidic glycoprotein(s) (mol wt, 200 to 285 kilodaltons [kD]; isoelectric point range [pl], 4.5 to 6.0) not observed in the wild-type or DMSO-resistant cells and, conversely, the presence of a lower molecular weight glycoprotein(s) (mol wt, 120 to 165 kD; pl, 4.2 to 5.9) in the wild-type and DMSO-resistant cells, which was absent or much reduced in the RA- and 6TG-resistant cells. These acidic SMGs did not change as a function of the induction of granulocyte differentiation. However, some other more basic SMGs varied as a function of granulocyte differentiation in both the wild-type and differentiation inducer-resistant sublines, including the loss of the transferrin receptor and the gain of a mol wt 55- to 60-kD neutrophil- associated protein. In the context of previously reported information, these results indicate (1) that the overall pattern of SMG changes in the RA- and 6TG-resistant cells closely resembles that associated with multidrug (pleiotropic) resistance to cytotoxic agents in a variety of mammalian cells; (2) that the RA/6TG resistance-associated SMG changes are not granulocyte differentiation stage-specific; and (3) that either the RA/6TG resistance-associated SMG changes are not related to the resistance mechanism or they are involved in the resistance/cross- resistance mechanism(s) for RA/purine bases but not for DMSO.
A single common electrophoretic abnormality of glucocorticoid receptors in human leukemia cells
Authors: Distelhorst CW , Benutto BM , Griffith RC 
Published: October 2019

Abstract
We determined the mol wt of glucocorticoid receptors in human leukemia cells in order to detect glucocorticoid receptor defects that might cause glucocorticoid resistance. Glucocorticoid receptors in intact cells were affinity labeled with [3H]dexamethasone-21-mesylate and were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Receptors in normal human peripheral blood mononuclear cells and six human leukemia cell lines had mol wt of 97,000. Malignant cells from ten of 25 patients with leukemia contained electrophoretically abnormal glucocorticoid receptors having mol wt of 55,000 in addition to normal size receptors (Mr = 97,000). The receptor abnormality was not restricted to a particular type of leukemia and was seen in cells from both newly diagnosed patients and patients who had received prior chemotherapy, including prednisone. The abnormal receptor was not generated when cells having only normal size receptors were assayed under conditions that favor proteolysis or when cytosol from cells containing the abnormal receptor form was mixed with cytosol from cells containing only normal size receptors. The mol wt of the abnormal receptors in human leukemia cells was the same as the mol wt of receptors in mutant mouse lymphoma cell lines, S49 143R and S49 55R, which have the nuclear transfer-increased phenotype of glucocorticoid resistance. This work describes for the first time a single common electrophoretic abnormality of glucocorticoid receptors in human leukemia cells. Further investigation of glucocorticoid receptor defects in human leukemia cells could lead to an improved understanding of the mechanisms of glucocorticoid resistance in leukemia as well as a method of predicting which patients are likely to be resistant to glucocorticoid therapy.
HTLV-III/LAV antibody status of spouses and household contacts assisting in home infusion of hemophilia patients
Authors: Lawrence DN , Jason JM , Bouhasin JD , McDougal JS , Knutsen AP , Evatt BL , Joist JH 
Published: October 2019

Abstract
Thirty-four adult and pediatric hemophilia A and B patients and 50 nonhemophilic members belonging to 28 families were enrolled in August 1984 in a study of human T cell lymphotropic virus type III/lymphadenopathy-associated virus (HTLV-III/LAV) antibody status and T cell subpopulation numbers. All 50 household contacts, including three spouses of LAV antibody-positive adult hemophiliacs, were immunologically normal and serologically negative with respect to HTLV- III/LAV. Based on Western blot serologic testing of blood samples collected intermittently between July 1981 and August 1984 from 33 representative St Louis hemophiliacs studied during the period from 1981 to 1984, the average time since seroconversion was estimated as 20 months. One spouse of a seropositive hemophiliac and 23 parents of 27 seropositive pediatric hemophiliacs assisted regularly with home infusions. These infusion assistants have collectively experienced 44 person-years of concentrate infusion “exposure” without seroconversion. These results suggest that the likelihood for transmission of HTLV- III/LAV from hemophiliacs to persons assisting in their therapy is extremely low.
Hemophilia B with inhibitor: molecular analysis of the subtotal deletion of the factor IX gene
Authors: Hassan HJ , Leonardi A , Guerriero R , Chelucci C , Cianetti L , Ciavarella N , Ranieri P , Pilolli D , Peschle C 
Published: October 2019

Abstract
The structure of factor IX gene was analyzed in a hemophilia B patient with inhibitor. Genomic DNA, digested with a variety of restriction endonucleases, was hybridized with the cDNA and various genomic factor IX probes. A large subtotal deletion of the gene was observed. The borders of the deletion span from a approximately 125 nucleotide region within the last exon to an unknown domain at least 7.5 kb upstream from the first exon: it thus involves approximately 33 kb of the factor IX locus. The abnormal gene was inherited by the daughter of the propositus, who showed both the normal and the deleted allele.
Ligand state of intraerythrocytic circulating HbC crystals in homozygote CC patients
Authors: Hirsch RE , Raventos-Suarez C , Olson JA , Nagel RL 
Published: October 2019

Abstract
Whole blood and Stractan-Percoll fractions of blood from splenectomized patients with homozygous hemoglobin C (CC) disease were studied under aerobic and anaerobic conditions. Erythrocytes containing typical CC crystals are found in the densest fraction as documented by freeze- fracture electron microscopy. We report that the intraerythrocytic Hb C circulating crystals are in the oxygenated liganded state as demonstrated by melting upon deoxygenation and by absorption spectroscopy. Furthermore, crystals are more likely to form in cells with low concentration of Hb F. Changes of ligand state (which results in melting of the intraerythrocytic crystal) might be involved in the pathophysiology of this disease, removing the danger of vasoocclusive episodes.
DNA sequence variation associated with elevated fetal G gamma globin production
Authors: Gilman JG , Huisman TH 
Published: October 2019

Abstract
The percentage of G gamma chains in the Hb F of SS patients and beta- thalassemia heterozygotes is generally 40%, but some have 60% to 70% G gamma. To test the hypothesis that DNA sequence variation 158 base pairs 5′ of the G gamma gene is associated with this variation in G gamma values, DNA was analyzed using the restriction endonuclease Xmn I (gamma IVS-II probe). Xmn I recognizes the sequence from -157 to -166 only if T is at position -158. Individuals from five families had T at - 158 for G gamma genes in both chromosomes, and the mean G gamma value was 69.7% +/- 4.6% (SD). For 13 families, individuals with T at -158 for the G gamma gene of one chromosome had a G gamma value of 60.6% +/- 5.7%. With one exception, lack of T at -158 was associated with low G gamma values (39.6% +/- 4.0%). In low Hb F G gamma-beta+-HPFH, the Xmn I site was seen 5′ to both G gamma and A gamma genes, which suggests that T at -158 is associated with elevated Hb F; Pst I digestion showed that the A gamma gene T producer G gamma globin, which accounts for high levels of G gamma (87–88%). Calculations show that T at -158 is associated with a three- to 11-fold increase in production per G gamma gene, which is an order of magnitude less than that associated with the previously identified -202 C----G substitution of high Hb F G gamma- beta+-HPFH.
Fetal hemoglobin variants identified in adults through restriction endonuclease gene mapping methodology
Authors: Nakatsuji T , Burnley MS , Huisman TH 
Published: October 2019

Abstract
It has been found possible to detect the presence of some gamma chain abnormal fetal hemoglobins in adults through analysis of genomic DNA with selected restriction endonucleases. These variants are Hb F-Hull (A gamma 121Glu----Lys) which was observed in eight adult members of five families, Hb F-Pendergrass (A gamma 36Pro----Arg) in five adult members of one family, and Hb F-Port Royal (G gamma 125Glu----Ala) in 32 adult members of 17 families. The analyses were extended to include haplotyping, which involved 12 different restriction sites. The Hb F- Port Royal anomaly was only present on a chromosome with two G gamma genes (the 5′-G gamma-G gamma-3′ globin gene arrangement) which may have arisen through gene conversion or point mutations. It appears likely that the mutation resulting in the 125Glu----Ala substitution occurred once on a 5′-G gamma-G gamma-3′ chromosome, while additional base substitutions, gene conversions, and/or cross-over events are responsible for the association of the F-Port Royal anomaly with different chromosomes, as characterized by different haplotypes.
The acetylcholinesterase defect in paroxysmal nocturnal hemoglobinuria: evidence that the enzyme is absent from the cell membrane
Authors: Chow FL , Telen MJ , Rosse WF 
Published: October 2019

Abstract
Paroxysmal nocturnal hemoglobinuria (PNH) is a myelodysplastic disease characterized by erythrocytes that show abnormally increased sensitivity to complement-mediated lysis. Complement-sensitive PNH erythrocyte membranes have previously been shown to lack acetylcholinesterase (AchE) activity, but the molecular basis of this deficiency has been unclear. We have used monoclonal antibodies to four different epitopes on the AchE molecule to show that abnormal PNH erythrocytes failed to bind these antibodies. Moreover, abnormal PNH erythrocytes contained no protein immunoprecipitable by these antibodies, while normal complement-insensitive erythrocytes from PNH patients showed normal amounts of immunoprecipitable AchE which had normal electrophoretic mobility. These data suggest that abnormal PNH erythrocytes lack AchE enzyme activity due to the absence of the AchE molecule from the cell membrane.
Peripheral T cell lymphoma: immunologic and cell-kinetic observations associated with morphological progression
Authors: Winberg CD , Sheibani K , Krance R , Rappaport H 
Published: October 2019

Abstract
Peripheral T cell lymphomas (PTCLs) form a morphologically heterogeneous group of non-Hodgkin's lymphomas that are generally considered to have immunophenotypes associated with mature T cells, usually those of helper T cells. We now describe and correlate the clinical, morphological, immunologic, and cell-kinetic findings based on the evaluation of eight tissue samples obtained at various times from a 13-year-old girl with PTCL. The early morphological expressions of this patient's PTCL were those of diffuse mixed-cell lymphoma and focal large-cell lymphoma (LCL) evolving from the histologic picture of an atypical immune response (AIR). These morphological findings were associated with an immature T cell immunophenotype associated with cortical thymocytes--namely, sheep erythrocyte rosette (sER)+, T11+, Leu-2a+, Leu-3a+, HLA-DR+, OKT6-, OKT9+, OKT10+--and with cell-kinetic findings that showed no evidence of aneuploidy and few cells in S phase. Diffuse pleomorphic LCL developed, which was associated with further dedifferentiation of the neoplastic T cells to the immunophenotype sER-, T11+, Leu-2a-, Leu-3a-, HLA-DR+, OKT6-, OKT9+, OKT10- and with cell-kinetic findings that demonstrated a distinct aneuploid population and a dramatic increase in the percentage of cells in the S phase. The immunophenotype of the PTCL at the time of the patient's death was T11-, Leu-2a-, Leu-3a-, HLA-DR+, OKT6-, OKT9+, OKT10-, an immunophenotype indistinguishable from that of a non-B non-T cell lymphoma. The immunologic findings in this case also suggest that an AIR in some cases may represent a prelymphomatous state or may be a morphological expression of PTCL. These observations indicate that PTCLs may be characterized by rapidly changing clinical, morphological, immunologic, and cell kinetic findings which are best evaluated by multidisciplinary studies.
Effect of natural killer cells on syngeneic bone marrow: in vitro and in vivo studies demonstrating graft failure due to NK cells in an identical twin treated by bone marrow transplantation
Authors: Goss GD , Wittwer MA , Bezwoda WR , Herman J , Rabson A , Seymour L , Derman DP , Mendelow B 
Published: October 2019

Abstract
Bone marrow transplantation for severe idiopathic aplastic anemia was undertaken in a patient, using his monozygotic twin brother as the donor. In spite of the use of syngeneic bone marrow, failure of engraftment occurred on two occasions. In vitro studies demonstrated that natural killer (NK) cells from the recipient markedly inhibited the growth of donor bone marrow granulocyte progenitor cells. On a third attempt, successful bone marrow engraftment was achieved following high-dose cyclophosphamide, which has previously been shown to be inhibitory to NK cells. We conclude that NK cell activity may play an important role in bone marrow failure as well as being responsible for at least some cases of aplastic anemia.