bluuebunny/crossref_metadata_2025_split huggingface dataset:
Heparin-induced thrombocytopenia: studies with a new low molecular weight heparinoid, Org 10172
Authors: Chong BH , Ismail F , Cade J , Gallus AS , Gordon S , Chesterman CN 
Published: October 2019

Abstract
Studies were performed to determine the cross-reaction rate of the heparin-dependent antibody with Org 10172, a new low molecular weight heparinoid, and to investigate the effect of Org 10172 on platelet activation induced by the antibody. The plasmas of 17 patients with thrombocytopenia induced by standard heparin were shown, by platelet aggregation studies, to contain the heparin-dependent antibody. Of these 17 patient plasmas, only three cross-reacted with the heparinoid, producing a cross-reaction rate of 18%. When Org 10172 was added to a reaction mixture containing normal platelet-rich plasma, patient plasma, and standard heparin with non-cross-reacting plasmas, it inhibited platelet aggregation and thromboxane B2 production induced by the antibody, provided that the ratio of Org 10172 concentration (anti- Xa U/mL) to standard heparin concentration (IU/mL) exceeded 2.5 to 5.0. This inhibitory effect was observed only with platelet activation mediated by the antibody, but not by collagen (2 micrograms/mL) or ADP (5.0 mumol/L). Additionally, three of 17 patients with serious thrombosis, whose plasma showed no cross-reaction with the heparinoid, received Org 10172 treatment with a good response in each case. These findings suggest that Org 10172 may be a useful drug for the treatment of heparin-induced thrombocytopenia.
Characterization of the blood group Kell (K1) antigen with a human monoclonal antibody
Authors: Jaber A , Blanchard D , Goossens D , Bloy C , Lambin P , Rouger P , Salmon C , Cartron JP 
Published: October 2019

Abstract
A human monoclonal anti-Kell (K1) antibody secreted by an Epstein-Barr virus (EBV)-transformed B-cell line was used for binding studies and immunopurification of the K1 blood group antigen. The 125I-labeled antibody bound to 4 to 5 x 10(3) and 2.5 to 3 x 10(3) antigenic sites on K1K1 and K1K2 erythrocytes, respectively, with an affinity constant of 5 x 10(8) mol/L-1. Immunoprecipitation analysis showed that the K1 antigen is carried by a 93 Kd glycoprotein containing several cysteine residues, and approximately six N-glycosidically linked sugar chains but no detectable O-linked sugar. A minor labeled component of 32 Kd was also immunoprecipitated from K1K1 RBCs but the 93- and 32-Kd components were absent from K2K2 and Kell null erythrocytes. Under nonreducing conditions, three bands were detected at 200 (weak), 120, and 93 Kd. We suggest that the 120-Kd component represents a heterodimer of the 93- and 32-Kd proteins covalently linked by disulfide bridge(s). The 93-Kd glycoprotein is a transmembrane component which interacts with the membrane skeleton but is distinct from band 3 as shown by one-dimensional peptide mapping. The site density of K1 antigen blood group on Gerbich-negative RBCs (Ge:-2,-3) was threefold lower than on K1K1 erythrocytes, but the qualitative properties of the 93-Kd component were not modified.
The T-cell receptor delta chain locus is disrupted in the T-ALL associated t(11;14)(p13;q11) translocation
Authors: Champagne E , Takihara Y , Sagman U , de Sousa J , Burrow S , Lewis WH , Mak TW , Minden MD 
Published: October 2019

Abstract
Two T-ALL patients carrying a t(11;14)(p13;q11) translocation were analyzed. Southern blotting experiments demonstrated that both patients had rearranged their J delta genes and that the translocation involved the delta locus in both cases. In one patient, cloning, restriction mapping, and sequencing showed that the translocation occurred on a D delta 1-D delta 2-J delta 2 rearranged gene. In addition, the rearrangement on chromosome 11 occurred in both patients within a segment of less than or equal to 2 kb showing the presence in this region of a point of recurrent recombination.
T cells from eosinophilic patients produce interleukin-5 with interleukin-2 stimulation
Authors: Enokihara H , Furusawa S , Nakakubo H , Kajitani H , Nagashima S , Saito K , Shishido H , Hitoshi Y , Takatsu K , Noma T 
Published: October 2019

Abstract
Anti-murine (m) interleukin-5 (IL-5) antibody was found to inhibit eosinophil (Eo) colony formation stimulated by recombinant human (rh) IL-5, but did not inhibit the production of Eo stimulated by rh IL-3 or granulocyte-macrophage colony-stimulating factor (GM-CSF). Conditioned medium (CM) prepared from eosinophilic patients' T cells with interleukin-2 (IL-2) stimulation (T-IL-2-CM), was found to contain CFU- Eo growth-stimulating factor. Using anti-mIL-5 antibody, we demonstrated that T-IL-2-CM from patients with eosinophilia contained a significant amount of IL-5. We also detected IL-5 mRNA in T cells from eosinophilic patients with IL-2 stimulation. These results suggest that IL-5 plays an important role in the induction of selective eosinophilia in humans and that IL-5 is produced from T cells with IL-2 stimulation.
Interleukin-6 interacts with interleukin-4 and other hematopoietic growth factors to selectively enhance the growth of megakaryocytic, erythroid, myeloid, and multipotential progenitor cells
Authors: Rennick D , Jackson J , Yang G , Wideman J , Lee F , Hudak S 
Published: October 2019

Abstract
The growth-promoting activities of interleukin-6 (IL-6) in combination with different factors were assessed in bone marrow (BM) cultures prepared from normal mice and from mice treated with 5-fluorouracil (5- FU). Effects on hematopoietic colony formation with respect to number, size, and cellular composition were evaluated. In agreement with previous reports, IL-6 acts synergistically with IL-3 to stimulate increased numbers of granulocyte/macrophage (GM) and multilineage colonies in day-2 and day-4 post-5-FU BM cultures. Furthermore, day 4 but not day 2 post-5-FU BM showed enhanced GM colony formation when stimulated with IL-6 plus interleukin-4 (IL-4) or granulocyte colony- stimulating factor (G-CSF). In contrast, IL-6 did not increase the number of colonies supported by M-CSF or GM-CSF. Nevertheless IL-6 interacted with all factors, including M-CSF and GM-CSF, to stimulate an increase in colony size. Many of these myeloid colonies attained a diameter of greater than or equal to 0.5 mm, suggesting they derive from high proliferative potential cells (HPP-CFC). The response of normal and day-8 post-5-FU BM containing high numbers of more mature progenitors was also assessed. We found IL-6 enhanced colony formation by lineage-restricted megakaryocytic and erythroid progenitors in the presence of IL-3 and IL-4 plus erythropoietin (Epo), respectively. The sum of these results shows that IL-6 interacts with a variety of factors to regulate the growth of progenitor cells at different stages of lineage commitment and maturation.
Relationship between human development and disappearance of unusually large von Willebrand factor multimers from plasma
Authors: Katz JA , Moake JL , McPherson PD , Weinstein MJ , Moise KJ , Carpenter RJ , Sala DJ 
Published: October 2019

Abstract
von Willebrand factor (vWF) multimers were examined in fetal, umbilical cord, and neonatal platelet-poor plasma (PPP) specimens. Sixty-five of 65 (100%) fetal PPP samples aged less than 35 weeks and seven of ten (70%) fetal samples aged greater than 35 weeks had unusually large vWF (ULvWF) multimers. Thirty of 46 (65%) cord PPP samples from neonates ranging in gestational age from 34 to 41 weeks had ULvWF. There was no significant relationship between either gestational age at time of delivery or birth weight and likelihood of finding ULvWF multimers in cord PPP samples. No maternal PPP sample contained ULvWF multimers. Serial heelstick samples from 16 preterm and term neonates were analyzed for 8 weeks. ULvWF multimers disappeared from the PPP of ten of the neonates during this time. The PPP of four neonates had vWF patterns similar to those in normal adult PPP throughout the sampling period. The ULvWF multimeric forms of fetal and neonatal PPP samples were similar to those constitutively released from endothelial cells. They were not as slowly migrating in a very porous 0.5% agarose gel system as the ULvWF multimers released from Weibel-Palade bodies in response to the calcium ionophore A23187. A vWF protomer was present in 97% of fetal samples, 83% of cord blood specimens, and 11% of neonatal heelstick samples, but was not found in any maternal sample. These results indicate that control mechanisms operative in older children and adults to prevent circulation of ULvWF multimers and vWF protomeric forms are normally acquired late in uterine life or during the neonatal period. ULvWF multimers, which are normal components of fetal, most cord, and some neonatal plasma samples, may contribute to in utero and postnatal hemostasis.
Factors influencing the acceleration of human factor XIa inactivation by antithrombin III
Authors: Scott CF , Colman RW 
Published: October 2019

Abstract
Controversy exists in the literature concerning the potentiating effect of heparin on the inactivation rate of factor XIa by antithrombin III (AT III) in both purified systems and in plasma. We have analyzed the factors that could influence this reaction and found that ionic strength of the medium, as well as the type and concentration of the heparin preparations accounted for the major discrepancies in the literature. At I = 0.43 N, a preparation of bovine lung heparin at 1 U/mL did not augment the inactivation rate of factor XIa by inhibitors in plasma or by purified AT III. However, when ionic strength was decreased, a progressive increase in the potentiating effect was observed, reaching 6.5-fold at I = 0.15 N. At saturating concentrations of heparin, which results in the formation of 100% AT III-heparin complex, (greater than ten-fold molar excess over AT III) in purified systems, all heparin preparations (porcine, bovine, low molecular weight [LMW], and high affinity) yielded an approximately 30-fold augmentation of the factor XIa inactivation rate. However, when heparin was less than saturating, we observed that various heparin preparations affected the AT III-induced inactivation of factor XIa to different degrees even though they exhibited the same inhibitory activity (1 U/mL) against thrombin. This variation resulted from differences in the number of AT III binding sites in each heparin preparation, despite a similar Kd for each. Addition of high molecular weight kininogen (HK) to AT III-heparin complexes did not enhance their ability to inhibit factor XIa, and high concentrations of HK decreased the inactivation rate. A high therapeutic dose of heparin only permits the formation of 2.5% to 16.5% of the AT III-heparin complexes that can be achieved at saturation. We observed that 1 U/mL heparin (bovine lung heparin) (high therapeutic concentration) in virtually undiluted plasma only accelerated the inactivation rate of factor XIa (in the absence of other active enzymes) less than two-fold. These new observations further support our previous conclusion that therapeutic levels of heparin have little to no influence on the inactivation rate of factor XIa in plasma.
The effect of peptides and monoclonal antibodies that bind to platelet glycoprotein IIb-IIIa complex on the development of clot tension
Authors: Cohen I , Burk DL , White JG 
Published: October 2019

Abstract
The development of tension in platelet-rich clots is a manifestation of fibrin polymer binding to platelets as well as platelet contractile activity. Arg-Gly-Asp(RGD)-containing peptides of fibrinogen alpha- chain and gamma-400–411 of fibrinogen gamma chain increased clot tension considerably, especially when it developed under isometric conditions. Morphometry revealed increased confluence of oriented fibrin and platelet aggregates. Monoclonal antibodies directed against different epitopes on the glycoprotein IIb-IIIa complex had varying effects on clot tension development. Monoclonal antibodies A2A9 and 7E3 inhibited clot tension while T10 and 10E5 increased it. Since neither peptides nor antibodies affected the platelet actomyosin ATPase activity, their effect on tension must reflect the interaction between platelets and polymerizing fibrin. We conclude that gamma-400–411 and RGD-peptides increase platelet-polymerizing fibrin interaction. This suggests that clot tension requires a platelet receptor for polymerizing fibrin, which is different from the fibrinogen receptor domain required for aggregation. The results with the monoclonal antibodies support this hypothesis.
Differential effects of interleukin-1 alpha and interleukin-1 beta on human peripheral blood eosinophils
Authors: Whitcomb EA , Dinarello CA , Pincus SH 
Published: October 2019

Abstract
Interleukin-1 (IL-1) plays a major role in the response to infection, inflammation, and immunological challenge. Eosinophils participate in the host response to parasitic infection and allergic and hypersensitivity diseases. The role of IL-1 in these disease states has not been extensively explored. We have reported that purified human monocyte derived IL-1 (mIL-1), a mixture of the two IL-1 forms but predominantly consisting of IL-1 beta, modulates eosinophil oxidative metabolism and enzyme secretion. Although the two major species of IL-1 (IL-1 alpha and IL-1 beta) have identical specific activities on T cells, we now report the selective effects of human recombinant IL-1 (hrIL-1) alpha and hrIL-1 beta on eosinophil function. Whereas hrIL-1 beta caused a significant increase in arylsulfatase secretion (235.4 +/- 29% of resting secretion, P less than or equal to .01) and beta- glucuronidase secretion (135.8 +/- 9.6% of resting secretion, P less than or equal to .02) similar to our experience with mIL-1, hrIL-1 alpha had no effect on enzyme secretion. However, a mixture of hrIL-1 alpha and hrIL-1 beta reproduced the ability of mIL-1 to inhibit the oxidative response to suboptimal doses of phorbol myristate acetate (PMA). When eosinophils were separated into subpopulations by density gradients, we found that eosinophil responses to IL-1 differed among the populations. These results suggest that eosinophil subpopulations respond selectively to each form of IL-1.
Tumor cell heterogeneity in multiple myeloma: antigenic, morphologic, and functional studies of cells from blood and bone marrow
Authors: King MA , Nelson DS 
Published: October 2019

Abstract
Tumor cells from six patients with immunoglobulin G (IgG) multiple myeloma were analyzed for surface antigens, cytoplasmic paraprotein, morphology, and response to various culture conditions. The tumor marker was the paraprotein idiotype. Low numbers of tumor cells were found in the blood of most of the patients. In some patients, the circulating tumor cells were solely B lymphocytes, whereas in other patients, they were lymphoid, lymphoplasmacytoid, and plasmacytoid. Dual surface antigen analysis of blood and bone marrow cells confirmed that the tumor may be composed of a spectrum of cell types. Thus, cells may range from surface-idiotype+,CD19+,CD20+, PCA-1-,cytoplasmic- idiotype- lymphocytes, to CD19-,PCA-1+,cytoplasmic-idiotype+ plasma cells that are surface-idiotype- or weakly surface-idiotype+. In one patient, some of the tumor cells co-expressed surface idiotype and CD10. The tumor B lymphocytes were activated in vitro to synthesize paraprotein by pokeweed mitogen (PWM), and by low molecular weight B cell growth factor (BCGF). In contrast, spontaneous synthesis of paraprotein by more mature tumor cells was inhibited by agents that also inhibit nonmyeloma plasma cells. These agents included PWM, gamma interferon, and phorbol ester. The results demonstrate that in multiple myeloma there exist different tumor cell types that are similar, by a variety of criteria, to normal B lineage cells at different stages of differentiation. Thus, further evidence is provided for the hypothesis of myeloma cell differentiation.
Immunocytochemical identification of meningeal leukemia and lymphoma: poly-L-lysine-coated slides permit multimarker analysis even with minute cerebrospinal fluid cell specimens
Authors: Kranz BR , Thiel E , Thierfelder S 
Published: October 2019

Abstract
Use of immunocytology for accurate identification of malignant cells in cerebrospinal fluid (CSF) has so far been hampered by high cell requirements of the immunologic methods hitherto used. In an attempt to minimize cell loss in cytopreparation, electrostatic binding of cells to poly-L-lysine (PLL)-coated multispot slides, followed by immunocytochemistry, was investigated. Using optimized conditions of cell attachment and fixation and performing all washing procedures on the slide made multimarker analysis possible even in paucicellular specimens, while preserving excellent cell morphology and yielding high sensitivity in the detection of antigens. In a study of 26 CSF specimens with inconclusive cytomorphology, comprising 335 single marker determinations, we were able to discriminate reliably between resting or activated benign cells and a wide range of types of malignant lymphoid cell. A definitive diagnosis was reached in all cases by one tap only. Malignant meningitis was ruled out in ten specimens and proved in 16, including five in which the type of malignancy could only be determined by immunophenotyping. We conclude that immunocytochemistry on PLL-coated slides constitutes the method of choice for immunologic cell differentiation in CSF, which allows equivocal morphologic findings to be clarified.
Expression of interleukin-2 receptor beta subunit in hematopoietic malignancies
Authors: Rosolen A , Nakanishi M , Poplack DG , Cole D , Quinones R , Reaman G , Trepel JB , Cotelingam JD , Sausville EA , Marti GE 
Published: October 2019

Abstract
The expression of the interleukin-2 (IL-2) receptor was studied in neoplastic cells derived from acute leukemias, T-cell lymphoblastic lymphomas, peripheral T-cell lymphomas, chronic lymphocytic leukemias, well-differentiated lymphocytic lymphomas, and established cell lines by both flow cytometric analysis and sodium dodecyl sulfate/polyacrylamide gel electrophoresis (SDS-PAGE) after affinity crosslinking of radiolabeled IL-2. Cells from most acute leukemias (19 of 22), irrespective of their subtype (T, common or nonlymphoid leukemias), as well as T-cell lymphoblastic lymphomas and peripheral T- cell lymphomas expressed only the p70–75 beta subunit of the IL-2 receptor. Cells from the more mature B-cell neoplasms, chronic lymphocytic leukemia, and well-differentiated lymphocytic lymphoma, expressed predominantly alpha beta IL-2 receptors (11 of 14). In contrast to these results, most cell lines established from hematopoietic malignancies do not express either chain of the IL-2 receptor. Further studies are necessary to determine the exact function of the IL-2R p70–75 beta subunit in immature hematopoietic cells, but its wide distribution throughout the hematopoietic system suggests that IL-2 may play a role in the early stages of hematopoiesis.
The mechanism of expansion of late erythroid progenitors during erythroid regeneration: target cells and effects of erythropoietin and interleukin-3
Authors: Umemura T , Papayannopoulou T , Stamatoyannopoulos G 
Published: October 2019

Abstract
Through immunologic means we have been able to separate primate bone marrow cells into populations containing late erythroid progenitors (colony forming units [CFUe] and e-clusters) but depleted of early erythroid progenitors (burst-forming units [BFUe]) or populations enriched in BFUe in relation to late progenitors. We used these fractionated populations in a two stage liquid/semisolid culture system and have assessed the effect of erythropoietin (Epo) and interleukin-3 (IL-3) on the proliferation and differentiation of erythroid progenitors in the presence or absence of early progenitors. We found that populations that contained CFUe but were depleted of BFUe failed to show any amplification of CFUe or e-clusters in the presence of Epo (or Epo plus IL-3). In contrast, populations containing BFUe yielded a striking (sixfold for CFUe; 23-fold for e-clusters) expansion of late progenitors in the presence of Epo. Maximum amplification (15-fold for CFUe; 32-fold for e-clusters) was achieved when both IL-3 and Epo were present in culture. Our results imply that CFUe and e-clusters lack the capacity to amplify their numbers and suggests that the expansion of late erythroid progenitors during rapid erythroid regeneration is accomplished by influx of BFUe rather than amplification of CFUe. These data are of relevance to models of acute marrow expansion and to the mechanism of activation of fetal hemoglobin production during rapid erythroid regeneration.
The t(5;14) chromosomal translocation in a case of acute lymphocytic leukemia joins the interleukin-3 gene to the immunoglobulin heavy chain gene
Authors: Grimaldi JC , Meeker TC 
Published: October 2019

Abstract
Chromosomal translocations have proven to be important markers of the genetic abnormalities central to the pathogenesis of cancer. By cloning chromosomal breakpoints one can identify activated proto-oncogenes. We have studied a case of B-lineage acute lymphocytic leukemia (ALL) that was associated with peripheral blood eosinophilia. The chromosomal translocation t(5;14) (q31;q32) from this sample was cloned and studied at the molecular level. This translocation joined the immunoglobulin heavy chain joining (Jh) region to the promotor region of the interleukin-3 (IL-3) gene in opposite transcriptional orientations. The data suggest that activation of the IL-3 gene by the enhancer of the immunoglobulin heavy chain gene may play a central role in the pathogenesis of this leukemia and the associated eosinophilia.
Treatment of progressive Hodgkin's disease with intensive chemoradiotherapy and autologous bone marrow transplantation
Authors: Phillips GL , Wolff SN , Herzig RH , Lazarus HM , Fay JW , Lin HS , Shina DC , Glasgow GP , Griffith RC , Lamb CW 
Published: October 2019

Abstract
Twenty-six patients with progressive Hodgkin's disease after conventional chemotherapy received intensive chemoradiotherapy and autologous bone marrow transplantation (ABMT); 19 also received additional involved-field radiotherapy. Twenty-one patients [81%, 95% confidence intervals (CI) 61% to 94%] attained complete (n = 18) or partial responses. Ten patients (38%, 95% CI 20% to 59%) are disease- free a median of 4.5 years later (range 3.5 to 7.0 years), including seven patients with continuous complete responses. The likelihood of overall response was not significantly influenced by any clinical or treatment variable examined. However, there was a trend favoring patients with higher Karnofsky scores, and higher scores were associated with attainment of complete responses (P = .06 and P = .02, respectively, Mann-Whitney U test). Both higher Karnofsky scores and shorter durations of disease before transplantation were associated with improved survival in a stepwise Cox multivariate analysis. The chief cause of failure was progression at sites previously involved with Hodgkin's disease. No patient relapsed in the marrow, and two of three patients with a history of marrow involvement with Hodgkin's disease achieved durable complete responses after transplantation. These data suggest that inadequate pretransplant conditioning, and not the reinoculation of occult tumor cells in the autologous marrow, caused most relapses. Fatal treatment-related toxicity occurred in six patients. Three patients died of idiopathic interstitial pneumonitis; each had previously received local mediastinal irradiation before intensive chemoradiotherapy. Intensive chemoradiotherapy and ABMT produces durable responses in some patients with Hodgkin's disease incurable with conventional therapy. Use of such therapies at the first sign of failure with conventional chemotherapy and development of more effective conditioning regimens should further improve results.