bluuebunny/crossref_metadata_2025_split huggingface dataset:
A variant of von Willebrand's disease characterized by recessive inheritance and missing triplet structure of von Willebrand factor multimers
Authors: Mannucci PM , Lombardi R , Pareti FI , Solinas S , Mazzucconi MG , Mariani G 
Published: October 2019

Abstract
A 10-yr-old girl had bleeding symptoms of moderate severity; her mother and maternal aunt had milder bleeding symptoms, and other members of the kindred were asymptomatic. In the child, factor VIII coagulant activity (VIII:C) and von Willebrand factor antigen (vWF:Ag) were normal, ristocetin cofactor very low, and the bleeding time (BT) markedly prolonged. These values were normal in the rest of the kindred, but the mother and maternal aunt had prolonged BT and a high VIII:C/vWF:Ag ratio. Crossed immunoelectrophoresis (CIE) showed a vWF:Ag peak migrating more anodally in the propositus, two distinct peaks, one migrating anodally, in the father, paternal uncle, and grandmother, and normal peaks in the rest of the kindred. In the propositus, analysis of vWF multimers in plasma on 1.6% sodium dodecyl sulfate (SDS) agarose revealed that there were no larger multimers and there was a relative increase of the smallest multimer. This relative increase was also seen in her relatives with a double peak on CIE. Using gels of smaller porosity, each multimer of the propositus's plasma consisted of a single band, instead of the repeating triplet seen in normal and von Willebrand's disease varients types IIA and IIB. The abnormalities found in the propositus are tentatively interpreted as being due to double heterozygosity for two different genes. The defective gene carried by the father affects the triplet structure of vWF multimers, whereas a prolonged BT and a high VII:C/vWF:Ag ratio are the only phenotypic expressions of the defective gene of the mother. The findings of aberrant triplet structure in congenital vWD strengthen the view that this structure is an intrinsic feature of the normal vWF molecule.
Histidine-rich glycoprotein is present in human platelets and is released following thrombin stimulation
Authors: Leung LL , Harpel PC , Nachman RL , Rabellino EM 
Published: October 2019

Abstract
Histidine-rich glycoprotein, and alpha 2-glycoprotein in human plasma, has been shown to interact with heparin, with the high-affinity lysine- binding site of plasminogen, with divalent cations, and is associated with the rosette formation between erythrocytes and lymphocytes. A specific enzyme-linked immunosorbent assay for histidine-rich glycoprotein has been developed and used to demonstrate that histidine- rich glycoprotein is present in human platelets. Histidine-rich glycoprotein was detected and quantified in detergent extracts of washed human platelets, with a mean level of 371 ng/10(9) platelets. Plasma histidine-rich glycoprotein, either in the platelet suspending medium or on the surface of the platelets, accounted for less than 3.4% of the detectable platelet histidine-rich glycoprotein. Histidine-rich glycoprotein was also demonstrated in human bone marrow megakaryocytes by immunofluorescence. The extent of histidine-rich glycoprotein release from platelets was dependent on the thrombin dose and correlated directly with the extent of serotonin release. The platelet and plasma histidine-rich glycoprotein were similar by immunochemical analysis. Anti-histidine-rich glycoprotein IgG did not inhibit platelet aggregation. Histidine-rich glycoprotein released by platelets following thrombin stimulation may play a significant role in modulating inflammatory events in the microenvironment of the platelet plug.
A granulocyte reactive monoclonal antibody, 1G10, identifies the Gal beta 1-4 (Fuc alpha 1-3)GlcNAc (X determinant) expressed in HL-60 cells on both glycolipid and glycoprotein molecules
Authors: Urdal DL , Brentnall TA , Bernstein ID , Hakomori SI 
Published: October 2019

Abstract
1G10, a monoclonal IgM antibody that identifies a differentiation antigen on human granulocytes and a subpopulation of monocytes, was found to react specifically with glycosphingolipids bearing the Gal beta 1–4(Fuc alpha 1–3)GlcNAc hapten (X determinant). This carbohydrate determinant was found on both glycolipid and glycoprotein molecules isolated from HL-60 cells (a promyelocytic leukemia cell line). Thus, this highly conserved carbohydrate-defined determinant previously described on mouse embryonic and mouse and human carcinoma cells is also expressed as a tissue-specific differentiation antigen on normal human granulocytes.
Erythropoietin production by a human testicular germ cell line
Authors: Ascensao JL , Gaylis F , Bronson D , Fraley EE , Zanjani ED 
Published: October 2019

Abstract
An established human testis germ cell line (1411-H) was found to produce significant amounts of erythropoietin (Ep), the primary regulator of erythropoiesis. Media conditioned by the 1411-H cells stimulated erythropoiesis both in vivo and in vitro. This activity was neutralized by anti-Ep. This continuous cell line provides a unique model for the study of the mechanisms of control of Ep biogenesis.
Regulatory mechanism of granulopoiesis in the bone marrow of CSF- producing tumor-bearing nude mice
Authors: Motoyoshi K , Suda T , Takaku F , Miura Y 
Published: October 2019

Abstract
The regulatory mechanism of differentiation of granulocyte and macrophage precursor cells (G/M CFU-C) in bone marrow and spleen obtained from nude mice bearing colony-stimulating factor (CSF) producing tumor (G-mice), which developed marked granulocytosis, was studied. In these mice, granulopoiesis is enhanced in the spleen, but suppressed in bone marrow. Coculture of G-mouse bone marrow cells with splenic cells of control nude mice (C-mice) and of G-mice resulted in 68% and 62%, respectively, more colonies than expected, while coculture of C-mouse bone marrow cells with these two sources of cell fractions resulted in only 2% and 11% more colonies. In the double-layer agar culture system, bone marrow and splenic cells of C- and G-mice produced a maximal number of colonies containing adequate amounts of human urinary CSF in the upper layer when C-mouse bone marrow cells were added to the lower layer, while these four sources of cells produced a moderate or minimal number of colonies when splenic cells of C- and G- mice or G-mouse bone marrow cells were added to the lower layer. Morphological examination of colonies formed in the upper layer revealed that addition of C-mouse bone marrow cells or irradiated G- mouse bone marrow cells to the lower layer resulted in a massive increment in the number of colonies with pure granulocytes and granulocyte and macrophage mixed (G + G/M) colonies formed by G-mouse bone marrow cells in the upper layer. However, the addition of irradiated C-mouse bone marrow cells or G-mouse bone marrow cells before irradiation to the lower layer did not change G + G/M colony formation by G-mouse bone marrow cells in the upper layer. We could reproduce these findings with conditioned media obtained from 3-day liquid cultures of these cell fractions. This suggests that a diffusible factor may be necessary for inhibition of G + G/M colony formation in G-mouse bone marrow cells. The fine mechanism of such inhibition remains to be clarified.
Adult hemoglobins are synthesized in murine fetal hepatic erythropoietic cells
Authors: Wong PM , Chung SW , White JS , Reicheld SM , Patterson M , Clarke BJ , Chui DH 
Published: October 2019

Abstract
The hemoglobins present in murine fetal hepatic erythroblasts on days 12–15 of gestation were studied by biochemical and immunocytologic techniques. In addition, fetal hepatic hemopoietic progenitor cells obtained from normal and mutant f/f mouse fetuses on days 11–13 of gestation were cultured in vitro with added erythropoietin and adult spleen cell conditioned medium to form large erythroid colonies. In all instances, adult hemoglobin synthesis was detected in the fetal hepatic erythroblasts and in the erythroid cell cultures in vitro. The tumor promoter, 12-O-tetradecanoylphorbol 13-acetate, enhanced the fetal hepatic erythroid colony growth in vitro, but did not alter the hemoglobin phenotypic expression.
Immunohistologic study of bone marrow involvement in B-chronic lymphocytic leukemia
Authors: Pizzolo G , Chilosi M , Ambrosetti A , Semenzato G , Fiore-Donati L , Perona G 
Published: October 2019

Abstract
Bone marrow trephine biopsies from 17 patients with B-chronic lymphocytic leukemia (B-CLL) were studied by immunohistologic techniques in order to investigate the cellular phenotypes of both neoplastic (B-lymphoid) and reactive (T-lymphoid) infiltrates. For this purpose, several heteroantisera and monoclonal antibodies against human Ig isotypes, HLA-DR antigens, and T-cell subpopulations were used in immunofluorescence. The findings were analyzed in relationship to the histologic pattern of involvement, as well as to the immunologic data of cell suspensions from peripheral blood. In all cases, the dominant lymphoid population within the bone marrow infiltrates showed identical phenotypic characteristics of B-CLL cells from the blood (HLA-DR+, mu +, most frequently delta +, kappa +, or lambda +, and weakly RFA-1+). The infiltration by these malignant B cells was diffuse in 5 cases and nodular plus interstitial in 12. The number of T cells (UCHT1+, RFA-1+, mu) was variable (5%-25%) in the different samples, but the values were high when compared to the proportion of T cells in normal bone marrow and in the blood of most patients studied. Furthermore, a clear predominance of T cells exhibiting the inducer phenotype (Leu-3+) was observed in all bone marrow samples, which is in contrast with the findings from peripheral blood, where T cells with the suppressor/cytotoxic phenotype (Leu-2+) were dominant. These data suggest a different blood and tissue distribution of inducer and suppressor/cytotoxic cells in B-CLL, which may have important pathophysiologic significance.
Allogeneic bone marrow transplantation as treatment for accelerating chronic myelogenous leukemia
Authors: McGlave PB , Arthur DC , Weisdorf D , Kim T , Goldman A , Hurd DD , Ramsay NK , Kersey JH 
Published: October 2019

Abstract
Sixteen patients with chronic myelogenous leukemia (CML) underwent allogeneic bone marrow transplantation (BMT) when they presented with or developed objective signs suggesting acceleration of disease. Patients have been followed for a median of 515 days (range 216–806 days). Seven patients are alive from 319 to 732 days (median 538 days). Four patients are in complete remission 501–732 days after BMT. Three patients have developed cytogenetic evidence of relapse after BMT; however, these patients are alive and not dependent on therapy and have normal activity levels at 319, 515, and 550 days following BMT. Three additional patients have developed cytogenetic and hematologic evidence of relapse after BMT, progressed to blast crisis, and died. Six patients have died of other causes. Allogeneic BMT can eradicate the abnormal clone and provide normal hematopoiesis when performed during the accelerated phase of CML; however, this approach is associated with relapse and with relatively high mortality. The long-term efficacy of this approach and the relative efficacy of transplant during acceleration rather than during the chronic phase of CML have yet to be established.
Potential role of platelets in the pathogenesis of tumor metastasis
Authors: Mehta P 
Published: October 2019

Abstract
Platelet activity may be involved in tumor metastasis. The tumor cells, after detachment from the primary site, adhere to vascular endothelium at distant sites and proliferate. Platelets form aggregates with tumor cells in circulation, facilitating their adhesion to the vascular endothelium. Formation of platelet-tumor cell aggregates and their sequestration in various end-organs may result in thrombocytopenia. Certain tumor cell lines directly stimulate platelet activity, some by releasing platelet-aggregating material, a urea-extractable membrane component, others by release of cathepsin, and still others by undefined mechanisms. The direct effect of platelets on tumor cells may be of pathogenic significance. For example, platelet-derived factors stimulate growth of some tumors, whereas others increase vascular permeability and thus facilitate migration of tumor cells across the vessel wall. Lack of these platelet factors, as in thrombocytopenic animals, may indeed inhibit tumor metastasis. Arachidonic acid metabolism in platelets and the vessel walls may contribute to metastatic process. In particular, thromboxane A2 and prostacyclin generation capabilities appear to be important in modulating platelet- tumor cell deposition and growth. To alter the metastatic process, several preliminary trials of platelet-inhibitory agents have been performed. However, the results of these trials have been equivocal, perhaps related to nonspecific effects of these agents on arachidonic acid metabolism. Studies directed at specific pathways of platelet- vessel wall interaction on some tumors appear promising. These newer agents may be of therapeutic value in man.
Anomalous function of vimentin in chronic lymphocytic leukemia lymphocytes
Authors: Stark RS , Liebes LF , Shelanski ML , Silber R 
Published: October 2019

Abstract
Chronic lymphocytic leukemia (CLL) lymphocytes manifest anomalous motility and cap formation. Since these processes involve cytoskeletal proteins, vimentin from intermediate filaments of normal and CLL lymphocytes was investigated using hetero- and monoclonal antisera. The antisera reacted predominantly with a 60-kD polypeptide, following sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of total lymphocyte proteins. When lymphocytes were stained by indirect immunofluorescence, normal lymphocytes demonstrated well defined cytoplasmic fibrils that capped spontaneously after contact with a glass surface and incubation at 37 degrees C. This capping was dependent on energy and intact microfilaments. Lymphocytes from patients with CLL showed several patterns. In one group, the initial staining was weak, and few capped cells were present after incubation. Lymphocytes from other patients had either normal or aberrantly organized fibrils in which capping was diminished. In another group, a fibrillar pattern with normal or increased capping was seen. In total, 47% +/- 5.1% (mean +/- SE) of normal lymphocytes capped after a 1-hr incubation at 37 degrees C (n = 12) compared to 21% +/- 5.1% for CLL lymphocytes (n = 20, p less than 0.002). Purified subpopulations of normal B and T cells did not differ from unfractionated normal lymphocyte populations. These results demonstrate an anomalous vimentin capping response in CLL lymphocytes. They also show that the arrangement of vimentin in these cells differs from that of normal lymphocytes.
Isolation and characterization of a T lymphocyte-derived differentiation inducing factor for the myeloid leukemic cell line HL- 60
Authors: Olsson IL , Sarngadharan MG , Breitman TR , Gallo RC 
Published: October 2019

Abstract
Mitogen-stimulated mononuclear blood cells produce differentiation inducing factors (DIFs) for the promyelocytic cell line HL-60. We report that DIF is produced constitutively by a malignant T lymphocyte line HUT-102. DIF was purified 7,000-fold from HUT-102 conditioned media by utilizing ion-exchange chromatography with DEAE-Sepharose, gel chromatography, Blue-Sepharose chromatography, and preparative SDS- polyacrylamide gel electrophoresis (SDS-PAGE). The final preparation is susceptible to protease treatment, has a molecular weight of 46,000, as determined by SDS-PAGE and approximately 55,000 by gel filtration, has an isoelectric point of approximately 5.2, does not adhere to lectin- Sepharose and is resistant to periodate oxidation, and is free of colony-stimulating factor. DIF induced maturation of HL-60 into phagocytizing nitro blue tetrazolium reducing cells with the morphological characteristics of myelomonocytic or monocyte-like cells. An activity, co-chromatographing with DIF, acts synergistically with retinoic acid to induce maturation not only of HL-60, but also of the monoblast-like cell line U-937 (measured as percentage of cells reducing NBT).
The effect of DDAVP on plasma levels of von Willebrand antigen II in normal individuals and patients with von Willebrand's disease
Authors: McCarroll DR , Ruggeri ZM , Montgomery RR 
Published: October 2019

Abstract
The infusion of 1-deamino-(8-D-arginine)-vasopressin (DDAVP) causes not only an elevation in factor VIII-related antigen (FVIIIR:Ag), but also a marked elevation of plasma von Willebrand antigen II (vWAgII). vWAgII reaches a peak concentration at 60 min and is elevated 3–8-fold over basal levels in normal individuals and individuals with type I, IIA, and IIB von Willebrand's disease. As the mechanism of hemostatic alteration brought about by DDAVP might be due to release of endothelial cell proteins, endothelial cell cultures were performed. The cultures demonstrated synthesis and secretion of vWAgII, as evidenced by the incorporation of 35S-methionine into the vWAgII molecule. Thus, vWAgII, like FVIIIR:Ag, is an endothelial cell protein.
Platelet storage pool deficiency in mouse pigment mutations associated with seven distinct genetic loci
Authors: Novak EK , Hui SW , Swank RT 
Published: October 2019

Abstract
Seven mouse pigment mutants, which have alterations at distinct genes, are known to have a defect in kidney lysosomal enzyme secretion. Two of these, beige and pale ear, have a bleeding abnormality associated with a deficiency in the number of platelet dense granules. In the present study, five other mutants with defective lysosomal enzyme secretion-- pearl, pallid, light ear, maroon, and ruby-eye--were likewise found to have abnormally prolonged bleeding times after experimental injury. Platelet counts were similar to those of normal mice, but the platelet dense granule components serotonin, adenosine triphosphate (ATP), and adenosine diphosphate (ADP) and morphologically identifiable dense granules were markedly reduced in these mutants. The capacity to accumulate exogenous 3H-serotonin in platelets was reduced 2–3-fold. Thrombin-stimulated secretion of 3H-serotonin was slightly decreased in all mutants. However, the seven mutants could be subdivided into three groups based on the degree of secretion of lysosomal enzymes after thrombin stimulation. Thus, all seven mouse pigment mutants have symptoms consistent with platelet storage pool deficiency and may serve as useful animal models for specific types of human platelet storage pool disease. Also, the results emphasize the genetic, morphological, and functional interrelatedness of three organelles: melanosomes, lysosomes, and platelet dense granules.
Cytotoxicity of platelet activating factor and related alkyl- phospholipid analogs in human leukemia cells, polymorphonuclear neutrophils, and skin fibroblasts
Authors: Hoffman DR , Hajdu J , Snyder F 
Published: October 2019

Abstract
A series of 11 alkyl-phospholipid analogs, structurally related to platelet activating factor (L-PAF), were analyzed for cytotoxic activity in human leukemic (HL-60) cells, human polymorphonuclear neutrophils, and Detroit 551 human skin fibroblasts. The order of selectiveness of the analogs in their cytotoxic response toward HL-60 cells in comparison to neutrophils is 1-alkyl-2-acetamide-GPC greater than 1-alkyl-2-methoxy-GPC greater than D-PAF greater than 1-acyl-2- lyso-GPC greater than 1-alkyl-2-lyso-GPC greater than L-PAF. A time- sequenced progression of events caused by the most potent cytotoxic alkyl-phospholipid analogs was characterized by (a) a rapid decrease in the cellular uptake and incorporation of 3H-thymidine into DNA that was detectable 4 hr after exposure to the analog, (b) a release of lactate dehydrogenase activity into the media at 8 hr after exposure, and (c) a decrease in cell number due to cell death that begins at 12 hr after exposure. Treatment of HL-60 cells with 1-alkyl-2-methoxy-GPC for 1 hr destroyed 40% of the cells after a subsequent 24-hr incubation period. The varied biologic activities of L-PAF, including how it affects serotonin release from platelets, blood pressure in rats, and cytotoxic responses in normal and leukemic cells, are discussed in relation to its D-enantiomer, 3-alkyl-2-acetyl-GPC, and the 2-acetamide analog. This report characterizes the kinetic events of the cellular responses in both normal and HL-60 cells in relation to the antineoplastic activities of unnatural ether-linked phospholipid analogs that are structurally related to L-PAF.
Human megakaryocytes. III. Characterization in myeloproliferative disorders
Authors: Rabellino EM , Levene RB , Nachman RL , Leung LL 
Published: October 2019

Abstract
Abnormal proliferation of the megakaryocytic line was observed in the marrow tissue from patients with myeloproliferative disorders. Megakaryocytes were identified by immunofluorescence using distinct platelet protein markers. Plasma factor VIII antigen (factor VIII:AGN) and platelet glycoproteins IIb and IIIa were detected in normal mature and early megakaryocytes, as well as in a morphologically heterogeneous population of low density marrow cells regarded as atypical megakaryocytes. Atypical megakaryocytes were defined as oval/round 14- 35-micron diameter blast-like mononuclear/multinucleated cells bearing platelet protein markers with distinct morphological features, including cytoplasmic vacuolation, variable nuclear/cytoplasmic ratios, and variable cytoplasmic granulation. Atypical megakaryocytes were observed in most chronic myelogenous leukemia (CML) patients and in two patients with polycythemia vera, representing between 60 and 1,840 cells/10(4) cells (less than 1.050 g Percoll/cu cm). No atypical megakaryocytes were found in (a) 20 normal controls, (b) two patients with essential thrombocythemia, (c) a patient with thrombocytosis secondary to acute bleeding, and (d) in two patients with CML. Atypical megakaryocytes appear to represent a single-cell population, as demonstrated by a series of double immunofluorescence assays using combinations of five different antiplatelet protein sera. There was a statistically significant correlation between the frequency of atypical megakaryocytes and the presence of immature forms of myeloid cells in blood. Analyses of Fc IgG receptors conducted with two different immunofluorescence systems have demonstrated that phenotypic similarities existed between atypical megakaryocytes and myeloproliferative platelet proteins and differentiation markers on megakaryocytes are useful in elucidating the pathophysiologic alterations occurring in the megakaryocytic compartment in patients with myeloproliferative disorders.
Diminished activity of a chemotactic inhibitor in synovial fluids from patients with familial Mediterranean fever
Authors: Matzner Y , Partridge RE , Levy M , Babior BM 
Published: October 2019

Abstract
Synovial fluids from patients with osteoarthritis contain a chemotactic inhibitor that acts by antagonizing the complement-derived chemotactic anaphylotoxin, C5a. The activity of this inhibitor in synovial fluids from patients with several forms of inflammatory arthritis (rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis, and gout) were comparable to the activity present in osteoarthritic synovial fluids. In contrast, levels of inhibitory activity in synovial fluids from 9 patients with familial Mediterranean fever were decreased to less than 20% of those found in osteoarthritis fluids. The possibility was considered that the diminished inhibitory activity in fluids from patients with familial Mediterranean fever plays a part in the pathogenesis of the inflammatory attacks characteristic of this disease.