bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cytochemical, immunologic, chromosomal, and molecular genetic analysis of a novel cell line derived from Hodgkin's disease
Authors: Kamesaki H , Fukuhara S , Tatsumi E , Uchino H , Yamabe H , Miwa H , Shirakawa S , Hatanaka M , Honjo T 
Published: October 2019

Abstract
A novel cell line, KM-H2, was established from the pleural effusion of a patient with Hodgkin's disease of mixed cellular type. Multiple phenotypic studies were carried out with this cell line. Acid phosphatase and nonspecific esterase activities were detected. Rosette formation with T lymphocytes and the receptors for C3b and Fc portion of IgG were positive. Among the antigens tested with a total of 22 monoclonal antibodies defining hematopoietic cell subsets or lineages, Ki-1, Leu-M1, MCS1, HLA-DR, and OKT9 antigens were found to be positive. The other antigens reportedly specific for T cells, B cells, natural killer (NK) cells, monocytes, interdigitating reticulum (IR) cells and dendritic reticulum cells were negative. These phenotypic features were identical to those of the Sternberg-Reed (SR) and Hodgkin (H) cells in the fresh materials reported by other researchers. Moreover, the KM-H2 cells and the parental pleural effusion cells shared several structural chromosome anomalies. These findings indicated that the KM-H2 cells are derived from the SR and H cells. Molecular genetic analysis of the KM-H2 cells disclosed that the human immunoglobulin JH gene was rearranged but not the JK gene, and that the human T cell receptor beta chain gene was of the germline type. Based on these properties of the KM-H2 cells, Hodgkin's disease may be derived from a cell lineage other than T cell or B cell.
The percentage of dense red cells does not predict incidence of sickle cell painful crisis
Authors: Billett HH , Kim K , Fabry ME , Nagel RL 
Published: October 2019

Abstract
To test the hypothesis that the tendency of hemoglobin S (HbS) to polymerize within cells is the major determinant of the incidence of vaso-occlusive episodes, we have examined the effect of the percentage of dense cells (as measured by Percoll-Stractan continuous density gradient centrifugation) on the frequency of painful crises in a group of 36 patients with sickle cell disease. No correlation was found between the percentage of dense cells and admissions for crisis. Among the patients with known alpha-gene status (n = 25), the strong correlation between decreased dense cells and alpha-thalassemia (- alpha/alpha alpha) reported previously was confirmed (P less than .001). In addition, in this small subset, patients with alpha- thalassemia (-alpha/alpha alpha) appeared to have a marginally increased number of admissions for sickle cell crisis (t = 2.1910, P less than .05), which was independent of the percentage of dense cells. We conclude that the percentage of dense sickle cells cannot predict the incidence of painful crisis, suggesting that other factors (microcirculatory regulation or other humoral and cellular factors) are more important in the generation maintenance of painful crises than the necessary, but not sufficient, tendency of HbS-containing red cells to sickle.
Platelet membrane microparticles in blood bank fresh frozen plasma and cryoprecipitate
Authors: George JN , Pickett EB , Heinz R 
Published: October 2019

Abstract
Cryoprecipitate has been demonstrated to correct the bleeding abnormality of patients with some congenital (storage pool disease) and acquired (uremia) platelet abnormalities, but the reason for this effect is unknown. We found significant platelet contamination in plasma harvested to prepare fresh frozen plasma and cryoprecipitate. The platelet membrane microparticles produced by freezing and thawing of the plasma were highly concentrated in cryoprecipitate and may contribute to its therapeutic effect.
Metabolism of ara-C by blast cells from patients with ANLL
Authors: Ross DD , Thompson BW , Joneckis CC , Akman SA , Schiffer CA 
Published: October 2019

Abstract
The dose-response relationship between extracellular concentration of cytosine arabinoside (ara-C) and intracellular formation of the putative active metabolites of ara-C [ara-C incorporation into DNA and intracellular pools of ara-C in triphosphate form (ara-CTP)] was investigated in blast cells obtained from patients with acute nonlymphocytic leukemia (ANLL) by exposing these cells in vitro to 10, 100, or 1,000 nmol/L of ara-C. We studied 23 untreated patients who subsequently achieved complete remission (CR) with a regimen using daunorubicin and conventional doses of ara-C (ara-C-sensitive group), and 30 patients judged to be ara-C-resistant either by failing initial induction therapy (16 patients) or by having relapsed on an ara-C- containing maintenance regimen (14 patients). In both patient groups, ara-C incorporation into DNA and intracellular ara-CTP both displayed statistically significant increases in response to increasing extracellular concentrations of ara-C (P = .0001 in both cases), with the rate of increase of ara-CTP greater than that of ara-C incorporation. Moreover, blast cells from all patients, even those who were most clinically resistant to ara-C, were able to form ara-CTP and to incorporate ara-C into DNA. Each tenfold increment in extracellular ara-C concentration caused an 8.5-fold increase in ara-CTP, but only a 3.6-fold increase in ara-C incorporation into DNA. Thus, the efficiency of incorporation of ara-C into DNA (defined as the ratio of ara-C incorporation to ara-CTP pools) decreased by 58% with each tenfold increment in the extracellular concentration of ara-C (P less than .0001), presumably as a result of the inhibitory effect of ara-CTP on DNA polymerase. Using an analysis of covariance, modest differences were found in the levels of the ara-C metabolite variables in the ara-C- sensitive group as compared with the resistant group. However, because there was considerable overlap in ara-C metabolite formation among the patient groups, it was not possible to predict clinical outcome by these in vitro assessments of ara-C metabolism.
Platelet aggregation by fibrinogen polymers crosslinked across the E domain
Authors: McManama G , Lindon JN , Kloczewiak M , Smith MA , Ware JA , Hawiger J , Merrill EW , Salzman EW 
Published: October 2019

Abstract
There is evidence that platelet interactions with artificial surfaces are mediated by plasma proteins, especially fibrinogen, adsorbed on the surfaces. Multiple site interactions between fibrinogen molecules adsorbed in high concentration and receptors in the unactivated platelet may be sufficient for platelet adhesion and subsequent activation. To examine this hypothesis, we prepared soluble polymers of fibrinogen. Polymers produced by interaction of fibrinogen with Fab'2 fragments of antibodies against fibrinogen's E (central) domain (Fg- Fab'2(E] induced, in gel-filtered platelets, aggregation and serotonin release, which were blocked by monoclonal antibodies against the GPIIb/IIIa complex, by Fab fragments against the D domain, and by metabolic inhibitors; aggregation was attenuated but not abolished by enzymatic removal of ADP (with CP/CPK) or by blockage of ADP binding sites (with FSBA), and when secretion was inhibited by aspirin. Fg- Fab'2(E) also induced a dose-dependent elevation in cytoplasmic Ca2+ (measured by Aequorin luminescence) which was attenuated by CP/CPK and by FSBA, and was eliminated by metabolic inhibitors and by anti- IIb/IIIa antibody. Fibrinogen complexes crosslinked with dimethylsuberimidate or Factor XIII neither aggregated gel-filtered platelets nor inhibited platelet aggregation by ADP and fibrinogen, probably because of inaccessibility of lysine residues in the D (terminal) domain of fibrinogen, which are thought to be required for platelet binding. Thus, soluble complexes of fibrinogen having multiple available platelet receptor recognition sites activate gel-filtered platelets and may provide a useful model for platelet-surface interactions mediated by adsorbed fibrinogen.
HLA-DR-associated invariant chain is highly expressed in chronic lymphocytic leukemia
Authors: Narni F , Kudo J , Mars W , Calabretta B , Florine DL , Barlogie B , Saunders GF 
Published: October 2019

Abstract
Total RNA extracted from peripheral blood lymphocytes of a patient with B-cell chronic lymphocytic leukemia (CLL) and the poly (A+) RNA was purified. A cDNA library was constructed and approximately 4,000 clones were screened in order to identify genes preferentially expressed in CLL. A relatively low repetition frequency characterizes the majority of the abundant mRNA species present in CLL lymphocytes. One clone, corresponding to the mRNA encoding the HLA-DR-associated invariant chain, was selected and its expression was examined in different leukemic cell populations and in normal tissues. DNA-RNA hybridization studies showed that the invariant chain mRNA (In-mRNA) is detectable in RNA preparations from human blood cells and their precursors, whereas no In-mRNA is found in several other tissues examined. Among various normal and leukemic leukocyte populations, the highest levels of In- mRNA are found in CLL. Therefore, a role of In-chain mRNA as a marker of CLL is proposed. Our data support a relationship between high levels of invariant chain mRNA and the out of cycle condition of CLL peripheral blood lymphocytes.
The relation of platelet density to platelet age: survival of low- and high-density 111indium-labeled platelets in baboons
Authors: Savage B , McFadden PR , Hanson SR , Harker LA 
Published: October 2019

Abstract
The relationship between platelet density and platelet age has been studied using continuous linear Percoll density gradients and 111In- labeling of autologous platelets in baboons. To investigate changes in platelet density during senescence in the circulation, baboons were infused with 111In-labeled autologous platelets, and blood was collected at one hour postinfusion and twice daily thereafter for six days. Platelets were isolated from these samples in high yield (greater than 95%) and separated in continuous linear Percoll density gradients following density equilibrium centrifugation. Although at one hour postinfusion the density distribution of radiolabeled platelets coincided closely with the distribution of the total platelet population, a detectable symmetrical shift toward higher densities was observed after five days. The relative specific radioactivity (RSR) of high-density platelets (1.064 to 1.067 g/mL) decreased at a slower rate than that of the total platelet population (platelets of all densities), whereas the RSR of low-density platelets (1.053 to 1.056 g/mL) showed a more immediate and rapid decrease. These results give rise to one of two interpretations: (1) low-density platelets have a shorter survival time than more dense platelets and are therefore cleared from the circulation at a faster rate, or (2) platelets of all densities increase in density upon aging in the circulation. To determine the explanation for changing RSR of different density fractions we studied the in vivo disappearance characteristics of low- and high-density 111In-labeled platelets. There were no significant differences between the mean survival times of low-density platelets (5.0 +/- 0.49 days, +/- 1 SD, n = 6), high-density platelets (4.9 +/- 0.56 days, n = 6), or control platelets representing platelets of all densities (4.9 +/- 0.38 days, n = 6). Although a slight increase in the density of all platelets during platelet senescence is indicated by these studies, we conclude that platelet density heterogeneity is not primarily a consequence of age-related changes in platelet density.
Production and characterization of a monoclonal antibody reactive with a specific neoantigenic determinant (comprising B beta 54-118) in degradation products of fibrin and of fibrinogen
Authors: Koppert PW , Koopman J , Haverkate F , Nieuwenhuizen W 
Published: October 2019

Abstract
Balb/c mice were immunized with a mixture of fibrin degradation products (XDPs) prepared by complete lysis of a human blood clot by tissue-type plasminogen activator and purified by immunoaffinity chromatography. Spleen cells of the mice were fused with P3 X 63 Ag 8653 myeloma cells. A clone (FDP 14) was selected that produces monoclonal antibodies (MoAbs) of the IgG1 kappa type that react with a neoantigenic determinant exposed in these XDPs, but not in intact fibrinogen or in fibrin monomers. Furthermore, the MoAb is reactive with some pure, individual degradation products of fibrinogen (fragments X, Y, E, and the N-terminal disulphide knot) and with the fibrinogen B beta-chain but not with A alpha- and gamma-chains or with fragments D, FCB-2 and FCB-3. Comparison of the known primary structures of these fibrinogen fragments indicates that the stretch B beta 54–118 comprises at least an important part of the epitope recognized by FDP-14. Apparently, this stretch contributes importantly to a neoantigenic determinant that is not functional in intact fibrinogen and fibrin monomer and that can be made functional by reduction of fibrinogen, or by digestion with plasmin or CNBr.
Detection of in vitro and in vivo cleavage of high molecular weight kininogen in human plasma by immunoblotting with monoclonal antibodies
Authors: Berrettini M , Lammle B , White T , Heeb MJ , Schwarz HP , Zuraw B , Curd J , Griffin JH 
Published: October 2019

Abstract
Purified human high-mol-wt kininogen (HMWK), the cofactor of the contact phase of blood coagulation, migrated as a single band (approximately 110,000 mol wt) in a continuous buffer sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), but appeared as two separated bands (approximately 120,000 and 105,000 mol wt) when analyzed in a discontinuous buffer SDS-PAGE system. After elution from SDS polyacrylamide gels, each of the two bands showed coagulant activity. Six murine monoclonal antibodies (Mabs) against HMWK were produced and purified. In immunoblotting studies, three Mabs bound to the isolated alkylated heavy chain and one to the alkylated light chain of HMWK, whereas the remaining two bound only to the single-chain or unreduced two-chain molecule. None of the Mabs inhibited the clotting activity of HMWK or its binding to kaolin. Two of the Mabs, one directed against the light chain and one against the heavy chain, were used as specific probes to study HMWK in plasma samples using an immunoblotting technique. The anti-light chain Mab identified two distinct bands (approximately 120,000 and approximately 105,000 mol wt) in normal human plasma, but not in plasma from patients with hereditary HMWK deficiency. The anti-heavy chain Mab detected two additional bands (approximately 60,000 and approximately 54,000 mol wt) corresponding to low-mol-wt kininogen (LMWK) in normal plasma. A sensitive and specific quantitative immunoblotting assay of HMWK antigen in plasma was developed. Moreover, the immunoblotting technique with the anti-light chain Mab was used to detect the cleavage of HMWK in plasma samples after in vitro or in vivo activation of the contact system. The anti- light chain Mab demonstrated in vivo activation and cleavage of HMWK during an angioedema attack in a patient with hereditary angioedema and C1-inhibitor deficiency.
Determination of platelet antigens and glycoproteins in the human fetus
Authors: Gruel Y , Boizard B , Daffos F , Forestier F , Caen J , Wautier JL 
Published: October 2019

Abstract
The autosomal recessive transmission of Glanzmann's thrombasthenia (GT) and Bernard-Soulier syndrome (BSS), together with requests of families who already had children with these diseases, prompted us to investigate the feasibility of their antenatal diagnosis. The preliminary step leading to the early detection of GT or BSS was to characterize, in the normal human fetus, the platelet antigens and glycoproteins (GPs) and to define their normal amounts on the membrane surface. Blood samples from 32 fetuses between 18 to 26 weeks of gestation were collected by direct puncture of the umbilical vein using an ultrasound-guided needle. Polyclonal antibodies from human origin directed against PLA1, Leka antigens, and the GPIIb IIIa complex (IgGL), or murine monoclonal antibodies specific for GPIb (AN51, 6D1), GPIIIa (AP-3), or GPIIb IIIa (AP-2) were studied using platelet suspension immunofluorescence tests. The binding of each antibody was quantified using a cytofluorograph (Ortho 50H). PLA1 and Leka antigens were expressed in normal amounts on fetal platelets as early as 16 weeks of intrauterine life. The GPIIb IIIa complex quantified by polyclonal or monoclonal antibodies was in the same range in fetuses (IgGL = 427 +/- 23 AUF, AP-2 = 459.5 +/- 8.5; AP-3 = 536 +/- 14) and in adults (IgGL = 420 +/- 30; AP-2 = 498 +/- 11; AP-3 = 515 +/- 13). The platelet binding of antibodies that recognized GPIb was higher in fetuses (AN51 = 491.5 +/- 14; 6D1 = 479 +/- 15) than in adults (AN51 = 426.5 +/- 9; 6D1 = 449 +/- 8.7). These results suggest that immunological techniques can be applied as early as 18 weeks of gestation for the antenatal diagnosis of GT and BSS.
Shortened platelet half-life in multiple myeloma
Authors: Fritz E , Ludwig H , Scheithauer W , Sinzinger H 
Published: October 2019

Abstract
Various defects in platelet function have been reported as being associated with multiple myeloma. In 30 myeloma patients and 15 healthy controls, we investigated platelet survival using in vitro labeling of autologous platelets with 111indium-oxine and measuring the in vivo kinetics of the radioisotope. Significantly shortened platelet half- life in patients averaged 73 hours, while platelet half-life in the healthy controls averaged 107 hours. In myeloma patients, serum levels of thromboxane B2, beta-thromboglobulin, and platelet factor 4 were significantly elevated; aggregation indices were within the pathological range; platelet counts and spleen-liver indices, however, were comparable to those of the healthy control group. No statistical correlation was found between platelet half-life and paraprotein concentrations. Our findings suggest an initial--so far unexplained-- intravascular process of platelet activation and consumption that finally manifests in shortened platelet half-life. It seems that overt thrombocytopenia develops only when the compensatory capacity of the bone marrow finally becomes exhausted. Further studies should be able to elucidate the pathophysiologic processes involved.
Hexachlorocyclohexanes, potent stimuli of O2- production and calcium release in human polymorphonuclear leukocytes
Authors: Kuhns DB , Kaplan SS , Basford RE 
Published: October 2019

Abstract
alpha-, gamma-, and delta-Hexachlorocyclohexane (HCCH), but not the beta-isomer, are shown to be potent stimuli for the production of superoxide anion (O2-) and the release of calcium in human polymorphonuclear leukocytes (PMNs). Although O2- production occurs in the absence of exogenous divalent cations, calcium (0.5 mmol/L) enhances O2- production by 50%. In addition, gamma-HCCH-induced O2- production is sensitive (IC50–30–40 mumol/L) to inhibition by the putative intracellular antagonist, 8-(diethylamino)octyl-3,4,5- trimethoxybenzoate hydrochloride (TMB-8). Furthermore, it is shown that gamma-HCCH induces a marked loss of membrane-associated calcium as monitored by chlortetracycline fluorescence. This pool of calcium appears to encompass the same pool released by the formylated tripeptide, formylmethionylleucylphenylalanine (FMLP). We suggest that the HCCHs represent a new class of stimuli of O2- production and calcium mobilization in PMNs.
Pretreatment hematocrit as an independent prognostic variable in Hodgkin's disease
Authors: Jaffe HS , Cadman EC , Farber LR , Bertino JR 
Published: October 2019

Abstract
Pretreatment hematocrit in 117 advanced-stage Hodgkin's disease patients treated with a combined modality therapy program was evaluated as an independent prognostic variable with regard to survival and relapse-free survival. Age greater than 40 years, and multiple extranodal sites of involvement were found to be statistically significant independent negative prognostic factors with regard to survival. Pretreatment hematocrit, however, was not an independent negative prognostic variable.
Acquired thrombasthenia due to GPIIb/IIIa-specific platelet autoantibodies
Authors: Niessner H , Clemetson KJ , Panzer S , Mueller-Eckhardt C , Santoso S , Bettelheim P 
Published: October 2019

Abstract
An otherwise healthy woman developed a hemorrhagic diathesis with fluctuating clinical symptoms and laboratory findings, but without thrombocytopenia, over 8 years. In periods of bad clinical condition, a platelet defect, characteristic of thrombasthenia, was found. In contrast to classic thrombasthenia, electrophoresis of the patient's platelet membranes revealed normal amounts of glycoproteins IIb alpha, IIb beta, and IIIa in the normal positions. Monoclonal antibodies, specific for GPIIIa and GPIIb/IIIa, respectively, bound normally to the P1A1-positive platelets from the patient. Although no antibody and no platelet function inhibitor were evident in the autologous plasma, an IgG1 antibody that was bound to the patient's platelets and was directed against GPIIb/IIIa could be demonstrated. After elution from the patient's platelets, this antibody immunoprecipitated GPIIb (both subunits), IIIa, and a 200-kilodalton (kd) band (probably undissociated GPIIb/IIIa complex) from solubilized normal platelets, but did not react with thrombasthenic platelets. Adding the eluate from the patient's platelets to normal platelet-rich plasma immediately caused concentration-dependent inhibition of adenosine diphosphate (ADP)- induced and collagen-induced aggregation and also strong inhibition of ADP-stimulated fibrinogen binding. Because it was very unlikely from the patient's medical history that the antibody was caused by alloimmunization, the hemorrhagic diathesis must be interpreted as acquired thrombasthenia due to an anti-GPIIb/IIIa autoantibody.
Granulocyte-macrophage colony-stimulating factor enhances phagocytosis of bacteria by human neutrophils
Authors: Fleischmann J , Golde DW , Weisbart RH , Gasson JC 
Published: October 2019

Abstract
In order to determine whether human granulocyte-macrophage colony- stimulating factor (GM-CSF) can enhance phagocytosis, neutrophils were combined with Staphylococcus aureus (S aureus), and both the number of bacteria per neutrophil and the percent of neutrophils phagocytizing were assessed in the absence and presence of GM-CSF. Exposure to GM-CSF did not enable neutrophils to ingest unopsonized bacteria. When bacteria were opsonized with serum, both the number of bacteria per neutrophil and the percent of cells phagocytizing were increased by treatment with GM-CSF. Digestion of extracellular organisms by lysostaphin was used to substantiate phagocytosis. These results indicate that another effect of GM-CSF on the mature neutrophil is the enhancement of phagocytosis.