bluuebunny/crossref_metadata_2025_split huggingface dataset:
Retinoic acid cooperates with tumor necrosis factor and immune interferon in inducing differentiation and growth inhibition of the human promyelocytic leukemic cell line HL-60
Authors: Trinchieri G , Rosen M , Perussia B 
Published: October 2019

Abstract
In this study, we analyzed the effect of tumor necrosis factor (TNF) on retinoic acid (RA)-induced myeloid differentiation of the promyelocytic HL-60 leukemia cell line. We show that low concentrations of the two substances, almost inactive in inducing differentiation when used separately, induce differentiation when added simultaneously to the cell cultures. Cells simultaneously expressing both monocyte/macrophage phenotype (typically induced by TNF) and granulocyte characteristics (typically induced by RA) are induced by a combination of the two factors, indicating that TNF and RA potentiate each other's activity. The results obtained using immune interferon (IFN-gamma) in combination with the two inducers suggest that the mechanism of action of TNF and IFN-gamma are possibly different. The inhibitory effect of RA on the expression of HLA class I antigens and of the high-affinity Fc receptor is potentiated by TNF but completely reversed by rIFN-gamma.
Improved results of treatment of adult acute lymphoblastic leukemia
Authors: Linker CA , Levitt LJ , O'Donnell M , Ries CA , Link MP , Forman SJ , Farbstein MJ 
Published: October 2019

Abstract
We designed a treatment program to improve the outcome for adults with acute lymphoblastic leukemia (ALL). Treatment included a remission- induction phase followed by intensive alternating cycles of non-cross- resistant chemotherapy and prolonged oral maintenance therapy. Eighty- one consecutive previously untreated patients were entered on this study. Ninety-four percent of patients entered complete remission. A Kaplan-Meier analysis predicts that 53% +/- 9% (SEM) of patients in remission will remain free of disease at 3 years. Neither age, sex, WBC count, nor immunophenotype had a significant effect on remission duration. This program of intensive cyclical chemotherapy has improved the disease-free survival of patients with adult ALL.
Chromosome aberrations and clinical features of adult T cell leukemia- lymphoma not associated with human T cell leukemia virus type I
Authors: Shimoyama M , Abe T , Miyamoto K , Minato K , Tobinai K , Nagoshi H , Matsunaga M , Nomura T , Tsubota T , Ohnoshi T 
Published: October 2019

Abstract
Chromosome aberrations and clinical features of three patients with adult T cell leukemia-lymphoma (ATL) not associated with human T cell leukemia virus type I (HTLV-I) are described. From their clinical features, two patients were diagnosed as acute type and one patient was diagnosed as chronic type, which later converted to acute crisis. Clonal and many chromosomal abnormalities were observed before therapy in the two acute type cases and at relapse in the chronic type case. Karyotype aberrations, including trisomy 3, trisomy 7, trisomy 21, del(6)(q21), del(10)(p13), 14q11 translocation, and loss of X chromosome, all of which are frequently found in HTLV-I associated ATL, were also seen in these cases of HTLV-I-negative ATL.
Heparin binding defect in a new antithrombin III variant: Rouen, 47 Arg to His
Authors: Owen MC , Borg JY , Soria C , Soria J , Caen J , Carrell RW 
Published: October 2019

Abstract
Antithrombin III (AT-III) Rouen is a hereditary abnormal antithrombin with normal progressive inhibitory activity and reduced heparin cofactor activity. It was isolated from the plasma of a woman who suffered a sudden idiopathic sensorineural hearing loss and balance impairment. There was no familial history of thrombosis. By heparin- Sepharose chromatography, AT-III Rouen was separated from the normal antithrombin on elution with increasing concentrations of NaCl. AT-III Rouen eluted earlier than is normal at both pH 7.4 and pH 6.0. At the lower pH, the antithrombins bound more avidly to the column, with the abnormal AT-III eluting closer to the normal than at the higher pH. Two- dimensional peptide mapping of tryptic and Staphylococcus aureus V8 protease digests of carboxymethylated antithrombins was performed on thin-layer silica plates. The abnormal peptide was located by tryptophan staining, and amino acid analysis and sequence studies demonstrated a substitution of an arginine at residue 47 for a histidine. Results from this study suggest that replacement of arginine 47 by a partially positively charged histidine has less effect on the heparin binding affinity than dose replacing it with a neutral cysteine side chain as in AT-III Toyama, in which no heparin binding was observed. In addition, heparin binding per se is not a sufficient condition to activate AT-III.
Clinical investigation of human alpha interferon in chronic myelogenous leukemia
Authors: Talpaz M , Kantarjian HM , McCredie KB , Keating MJ , Trujillo J , Gutterman J 
Published: October 2019

Abstract
Fifty-one patients with previously untreated or minimally treated chronic myelogenous leukemia in chronic phase received human alpha interferon 3 to 9 X 10(6) units intramuscularly (IM) daily until complete hematologic remission, then at doses ranging from 3 X 10(6) units every other day to 9 X 10(6) units daily. Forty-one (80%) patients achieved a hematologic response, 36 (71%) of them attaining a complete hematologic remission with normal peripheral WBC and differential counts. Responding patients showed continuous but slow normalization of several other blood and marrow parameters including platelet counts, serum lactic dehydrogenase and B12 levels, and marrow cellularity and maturation index. Suppression of the Philadelphia chromosome on serial cytogenetic studies of marrow metaphases was documented in 20 of the 36 patients who achieved complete hematologic remission (56%; 39% of total group), eight of whom (22%) had a decrease of the Philadelphia chromosome-positive metaphases to less than 35%. These changes were persistent for 6 months or longer in 18 patients, seven of whom had continuous suppression of the Philadelphia chromosome to less than 90% for a median of 30+ months (range 21+ to 39+ months). After a median follow-up period of 37 months, 25 patients remain in continued disease control with interferon therapy. The projected 3-year survival rate is 76%, with a yearly death rate of 6%, 9%, and 9% in the first 3 years. Response, Philadelphia chromosome suppression, and survival were significantly better among patients in the low-risk category compared to intermediate- and high-risk categories, as defined by a multivariate analysis-derived prognostic model. The projected 3- year survival rate was 94% for patients who achieved a complete hematologic remission on interferon therapy and 45% for those who did not. Thirteen patients have developed blastic crisis, six with lymphoid and three with undifferentiated morphology. We conclude that human leukocyte alpha interferon effectively controls chronic myeloid leukemia and allows reappearance of diploid hemopoietic cells in some patients.
Immature dense granules in platelets from mice with platelet storage pool disease
Authors: Reddington M , Novak EK , Hurley E , Medda C , McGarry MP , Swank RT 
Published: October 2019

Abstract
Mepacrine uptake into platelets and bone marrow megakaryocytes was analyzed to further characterize the dense granule defects in a group of seven mouse pigment mutants that have characteristics of platelet storage pool disease (SPD). In contrast to our previous studies using electron microscopy, this method revealed that all mutants had normal numbers of dense granules. However, total mepacrine uptake in all mutant platelets was significantly diminished to less than 50% of normal uptake. Also, the flashing phenomenon observed when normal dense granules are irradiated with ultraviolet light was either greatly diminished or absent when platelets of individual mutants were similarly irradiated. Therefore the principal defect in the mutant platelets is an inability to accumulate dense granule contents rather than an absence of the granules. Mepacrine uptake into megakaryocytes was indistinguishable in normal and mutant mice. This indicates the mutant dense granule defects appear either very late in megakaryocyte development or early in platelet formation in correlation with development of the mature dense granule. By standard transmission electron microscopy we have not been able to detect gross structural or subcellular abnormalities in either platelets or megakaryocytes of mutant mice. It appears all seven mutants produce immature or functionally abnormal dense granules.
The presence of clonogenic cells in high-grade malignant lymphoma: a prognostic factor
Authors: Tweeddale ME , Lim B , Jamal N , Robinson J , Zalcberg J , Lockwood G , Minden MD , Messner HA 
Published: October 2019

Abstract
A culture system has been developed that promotes growth of clonogenic lymphoma cells of some patients with intermediate and high-grade malignant lymphoma. The formation of colonies in bone marrow, lymph nodes, and peripheral blood samples is best supported by human plasma. Colony formation of some patients was dependent upon growth factors, which in this study were added in the form of medium conditioned by phytohemagglutinin (PHA)-stimulated leukocytes (PHA-LCM). Some gave rise to lymphoma colonies without PHA-LCM but improved their frequency with PHA-LCM; others were completely independent of PHA-LCM. Colonies grown in primary cultures were routinely recloned and propagated as Epstein-Barr virus (EBV)-negative cell lines with stable B cell phenotype. The cell lines showed the same immunoglobulin rearrangement pattern as that observed in the primary lymphoma sample. In addition, a significant clinical correlation was observed between culture data and clinical outcome. Survival of patients who formed lymphoma colonies at any time during their clinical course was significantly shorter than survival of patients who did not give rise to colonies (P = 0.0009). The same observation was made when the survival assessment was performed for the subset of patients studied at diagnosis (P = 0.0014).
Initiation and regulation of fibrinolysis in human plasma at the plasminogen activator level
Authors: Wun TC , Capuano A 
Published: October 2019

Abstract
The initiation and regulation of fibrinolysis has been studied by reconstitution of fibrinolytic activity in human plasma in vitro. Depletion of tissue plasminogen activator (tPA) antigen by immunoadsorption of human plasma with anti-tPA Ig Sepharose 4B leads to total loss of spontaneous fibrinolytic activity determined by lysis of a thrombin-induced clot. Addition of physiological concentrations of purified tPA to tPA-depleted plasma restores fibrinolytic activity as a function of the length of time between tPA addition and clotting. Addition of free tPA to tPA-depleted plasma followed by immediate clotting results in a high rate of fibrinolysis. In contrast, when free tPA is allowed to incubate in plasma for 10 to 60 minutes prior to clot formation, the fibrinolytic activity of tPA is gradually lost. The loss of tPA-induced fibrinolytic activity in unclotted plasma is accompanied by decreased partitioning of tPA antigen into fibrin after clotting and is kinetically correlated with the formation of a 100 kilodalton (kDa) tPA complex as demonstrated by SDS-gel electrophoresis and fibrin-agar zymography. These results suggest that free tPA is susceptible to complexation by the plasma inhibitor in the absence of a clot. Fibrin formation renders tPA relatively inaccessible to inhibition. The tPA antigen isolated from stored plasma consists mainly of 100 kDa activity in SDS-gel electrophoresis and zymography, indicating that the tPA complex is resistant to dissociation by SDS. Upon rezymography of the sliced gel, only a 60 kDa tPA activity is found, suggesting that the activity at 100 kDa is at least partly due to free tPA dissociated from the complex during the first zymography. Conversion of tPA complex to enzymatically active free tPA also occurs with brief SDS exposure followed by incubation in the presence of excess Triton X-100 or by hydroxylamine treatment. These results reconcile the apparent discrepancy of the 100 kDA inhibitor-tPA complex manifesting plasminogen activation activity during zymography. The plasma tPA- inhibitor complex is precipitated strongly by antisera against plasminogen activator inhibitors (PAIs) of human Hep G2 hepatoma and HT- 1080 fibrosarcoma cells and weakly by antiserum against bovine aortic endothelial cell PAI but not by antiserum against a placental PAI (PAI- 2) suggesting that the plasma inhibitor is immunologically related to Hep G2, HT-1080 and possibly endothedial cell PAIs. Based on the above findings, a simple model for the initiation and regulation of plasma fibrinolysis at the PA level has been formulated.
Purging leukemic cells from simulated human remission marrow with alkyl- lysophospholipid
Authors: Okamoto S , Olson AC , Vogler WR , Winton EF 
Published: October 2019

Abstract
Alkyl-lysophospholipids (ALP) are analogues of 2- lysophosphatidylcholine that have been reported to have selective antitumor activity. These compounds could potentially be useful in purging bone marrow of leukemic cells in autologous marrow transplantation in acute leukemia. To determine the efficacy of pharmacological purging by ALP, we have designed a human assay system to mimic the conditions expected in the clinical setting of autotransplantation using remission marrow. A simulated remission marrow (SRM) was prepared by mixing normal marrow cells and HL60 cells in a ratio of 1,000:1. The effect of cryopreservation on ALP-treated normal, HL60, and SRM cells was examined. In separate experiments, ALP significantly reduced the number of clonogenic HL60 cells with no effect on normal marrow progenitors. The effect of ALP was more apparent after cryopreservation. Incubation of HL60 cells with 50 micrograms/mL ALP for four hours followed by cryopreservation resulted approximately in a 3 log reduction of clonogenic HL60 cells. ALP also selectively purged the small number of leukemic cells from SRM. In SRM, the data suggested that ALP had indirect cytotoxic activity on leukemic cells by enhancing the cytotoxic activity of monocytes in addition to its direct effect. We found no evidence that clonogenic HL60 cells decreased because of induction of differentiation by ALP. These data indicated that treatment of marrow cells with ALP offers an efficient means to eliminate leukemic cells from the graft.
Factor XII gene alteration in Hageman trait detected by TaqI restriction enzyme
Authors: Bernardi F , Marchetti G , Patracchini P , del Senno L , Tripodi M , Fantoni A , Bartolai S , Vannini F , Felloni L , Rossi L 
Published: October 2019

Abstract
A cDNA for coagulation factor XII has been used to investigate the presence of gene lesions and restriction fragment length polymorphisms in two brothers with Hageman trait and their family. A TaqI polymorphic fragment has been found in the two propositi and in 11 members of the paternal lineage. This polymorphism, absent in the normal population, is correlated with the reduction of factor XII activity and enables the identification of heterozygous factor XII deficiency. Factor XII gene deletion as the cause of Hageman trait in this family has been excluded. A restriction map has been constructed, and the TaqI polymorphic site has been localized within the 5′ portion of the gene. The mutation in the polymorphic site is probably the cause of the factor XII deficiency. Data suggest the presence of one factor XII gene per haploid genome.
Evaluation of four methods for platelet compatibility testing
Authors: McFarland JG , Aster RH 
Published: October 2019

Abstract
Four platelet compatibility assays were performed on serum and platelet or lymphocyte samples from 38 closely HLA-matched donor/recipient pairs involved in 55 single-donor platelet transfusions. The 22 patients studied were refractory to transfusions of pooled random-donor platelets. Of the four assays (platelet suspension immunofluorescence, PSIFT; 51Cr release; microlymphocytotoxicity; and a monoclonal anti-IgG assay, MAIA), the MAIA was most predictive of platelet transfusion outcome (predictability, 74% for one-hour posttransfusion platelet recovery and 76% for 24-hour recovery). The only other assay to reach statistical significance was the PSIFT (63% predictability for one-hour posttransfusion recovery). The degree of HLA compatibility between donor and recipient (exact matches v those utilizing cross-reactive associations) was unrelated to the ability of the MAIA to predict transfusion results. The MAIA may be capable of differentiating HLA antibodies, ABO antibodies, and platelet-specific antibodies responsible for failure of HLA-matched and selectively mismatched single-donor platelet transfusions.
Kinetics of inhibition of human plasma kallikrein by a site-specific modified inhibitor Arg15-aprotinin: evaluation using a microplate system and comparison with other proteases
Authors: Scott CF , Wenzel HR , Tschesche HR , Colman RW 
Published: October 2019

Abstract
Human plasma kallikrein, a product of contact-activated plasma proteolysis, is moderately inhibited by aprotinin, a small polypeptide from bovine lung that has been used as an experimental drug in human disease states. Aprotinin has a Lys residue in the P1 (reactive center) position occupying residue 15. Since kallikrein is an arginine-directed serine protease, we hypothesized that an altered form of aprotinin, Arg15-aprotinin, might be a better inhibitor. Kinetic evaluations were performed in 96-well microplates. We found that the KL (loose or Michaelis-Menten complex) was unchanged by the modification. However, the association rate constant was increased from 1.14 X 10(4) (mol/L)- 1s-1 to 1.5 X 10(5) (mol/L)-1s1, thus indicating that the inhibition rate was increased 14-fold for the modified protein. The Ki (at equilibrium) was decreased from 3.2 X 10(-7) mol/L to 1.5 X 10(-8) mol/L after substituting Arg for Lys in the P1 position. Therefore, the modified inhibitor binds to plasma kallikrein more tightly than the natural protein. We also investigated the effect of Arg15-aprotinin on tissue kallikrein, plasmin, factor XIIa, factor XIa, and thrombin and found that the Ki slightly decreased from 5.1 X 10(-7) mol/L to 1.2 X 10(-7) mol/L for tissue kallikrein and slightly decreased from 2 X 10(- 8) mol/L to 1 X 10(-8) mol/L for plasmin. Arg15-aprotinin did not inhibit thrombin or factor XIIa, even though both enzymes are arginine- directed serine proteases. However, factor XIa, although it was not inhibited by aprotinin, had a Ki of 3.4 X 10(-8) mol/L for Arg15- aprotinin. Therefore, Arg15-aprotinin is a more effective inhibitor of plasma kallikrein as well as factor XIa but shows minimal preference for plasmin and tissue kallikrein. This study also indicates that it is possible and practical to perform kinetic analyses directly in microplates.
Posttransfusion purpura associated with an autoantibody directed against a previously undefined platelet antigen
Authors: Stricker RB , Lewis BH , Corash L , Shuman MA 
Published: October 2019

Abstract
Although alloantibody against the PLA1 platelet antigen is usually found in patients with posttransfusion purpura (PTP), the mechanism of destruction of the patient's own PLA1-negative platelets is unexplained. We used a sensitive immunoblot technique to detect antiplatelet antibodies in a patient with classic PTP. The patient's acute-phase serum contained antibodies against three proteins present in control (PLA1-positive) platelets: an antibody that bound to a previously unrecognized platelet protein of mol wt 120,000 [glycoprotein (GP) 120], antibodies that bound to PLA1 (mol wt 90,000), and an epitope of GP IIb (mol wt 140,000). The antibodies against PLA1 and GP IIb did not react with the patient's own PLA1-negative platelets, control PLA1-negative platelets, or thrombasthenic platelets. In contrast, the antibody against GP 120 recognized this protein in all three platelet preparations, but not in Bernard-Soulier or Leka (Baka)-negative platelets. Antibody against GP 120 was not detected in the patient's recovery serum, although the antibodies against PLA1 and GP IIb persisted. F(ab)2 prepared from the patient's acute-phase serum also bound to GP 120. These results suggest that in PTP, transient autoantibody production may be responsible for autologous (PLA1-negative) platelet destruction. In addition, alloantibodies against more than one platelet alloantigen may be found in this disease. The nature of the GP 120 autoantigen and the GP IIb- related alloantigen defined by our patient's serum remains to be determined.
FVIII inhibitor IgG subclass and FVIII polypeptide specificity determined by immunoblotting
Authors: Fulcher CA , de Graaf Mahoney S , Zimmerman TS 
Published: October 2019

Abstract
We used immunoblotting of purified factor VIII coagulant protein (FVIII) to localize FVIII inhibitor epitopes in 76 inhibitor plasmas to either the 92-kd FVIII polypeptide (and its 54-kd and/or 44-kd thrombin fragments), the 80-kd polypeptide (and its 72-kd thrombin fragment), or both of these polypeptides. We also used immunoblotting to examine the immunoglobulin class and subclass content of 12 inhibitors with monoclonal antibodies specific for human IgG subclasses and IgM. Seven hemophilic (alloantibody) and five spontaneous (autoantibody) inhibitors contained IgG-1 and IgG-4 antibody; one of the spontaneous inhibitors also contained IgG-3. In one hemophilic inhibitor, the IgG-4 component reacted strongly with the 92-kd and 80-kd polypeptides, whereas the IgG-1 component reacted only minimally with the 92-kd polypeptide although its reactivity with the 80-kd polypeptide was strong. Another hemophilic inhibitor was affinity purified and subjected to quantitative radial immunodiffusion, and the presence of IgG-1 and IgG-4 antibody was confirmed. We conclude that the inhibitors examined are not monoclonal but are probably of restricted polyclonal origin and that different IgG subclasses in an inhibitor plasma can have different degrees of FVIII polypeptide reactivity.
Glycoprotein Ib and glycoprotein IX are fully complexed in the intact platelet membrane
Authors: Du X , Beutler L , Ruan C , Castaldi PA , Berndt MC 
Published: October 2019

Abstract
Two new murine monoclonal antibodies, AK 1 and SZ 1, reactive with the human platelet glycoprotein (GP) Ib-IX complex have been produced by the hybridoma technique. Both AK 1 and SZ 1 immunoprecipitated the GP Ib-IX complex from Triton X-100-solubilized, periodate-labeled platelets. With trypsinized, labeled platelets, AK 1, SZ 1, and FMC 25 (epitope on GP IX) immunoprecipitated a membrane-bound proteolytic fragment of the GP Ib-IX complex consisting of GP IX and an congruent to 25,000 mol wt remnant of the alpha-chain of GP lb disulfide-linked to the beta-subunit. Unexpectedly, although AK 1 and SZ 1 immunoprecipitated purified GP Ib-IX complex, neither antibody immunoprecipitated the individual components of this complex, GP Ib or GP IX. When GP Ib and GP IX were recombined, however, AK 1 and SZ 1 again immunoprecipitated the reformed complex, strongly suggesting that both antibodies were recognizing an epitope present only on the intact complex. Cross-blocking studies indicated that AK 1 and SZ 1 recognized a very similar or identical epitope that was proximal to the epitope for FMC 25. Both AK 1 and SZ 1 bound to a similar number of binding sites (congruent to 25,000) on intact platelets as monoclonal antibodies directed against either GP lb or GP IX. The combined data suggests that GP lb and GP IX are fully complexed in the intact platelet membrane.