bluuebunny/crossref_metadata_2025_split huggingface dataset:
Thrombin pretreatment of human platelets impairs thromboxane A2 synthesis from endogenous precursors in the presence of normal cyclooxygenase activity
Authors: Reimers HJ , Scharf RE , Baker RK 
Published: October 2019

Abstract
Exposure of horse platelets to thrombin has been reported to cause nearly complete inactivation of cyclooxygenase within 30 sec. This contrasts with the observation that human platelets, depleted of their granule constituents by stimulation with thrombin, still aggregate in response to arachidonic acid, a reaction presumably mediated by thromboxane A2 (TxA2) formation. Because of this conflicting evidence, TxA2 formation was measured by radioimmunoassay in washed human platelets depleted of their alpha- and dense-storage granule constituents by prior stimulation with thrombin. These platelets aggregated in response to adenosine diphosphate (ADP), collagen, arachidonic acid, and thrombin, and formed TxA2. However, collagen- and thrombin-induced TxA2 formation by these platelets was reduced in comparison to control platelets that had not been depleted of their storage granule constituents by prior thrombin stimulation. In contrast, arachidonic acid-induced TxA2 formation was not significantly different in thrombin-depleted and control platelets. These results demonstrate that thrombin can induce degranulation of platelets without concomitant inactivation of cyclooxygenase.
Blastic transformation of essential thrombocythemia: dual expression of myelomonoblastic/megakaryoblastic phenotypes
Authors: Frei-Lahr D , Barton JC , Hoffman R , Burkett LL , Prchal JT 
Published: October 2019

Abstract
Three patients developed blastic transformation of essential thrombocythemia (tET). Morphological studies in all patients showed that the majority of blasts had either myeloblastic or myelomonoblastic differentiation. Immunologic assays of hematopoietic cells were performed in two patients. In patient 1, 86% of peripheral blood mononuclear cells (predominantly blasts) reacted with a monoclonal antibody specific for granulocytes and monocytes (MMA), and 15% of mononuclear cells reacted with Tab, a monoclonal antibody specific for megakaryocyte-platelet glycoproteins (PGP) IIb and IIIa. In patient 2, 41.5% of peripheral blood mononuclear cells (predominantly blasts) were MMA-positive, 22.5% were Tab-positive, and 40% reacted with rabbit anti- human PGP. These results suggest either that two subpopulations of blast cells exist in tET, or that blast cells simultaneously express surface markers of myeloblastic/monoblastic and megakaryoblastic differentiation. In these three and in nine previously reported cases of tET, neither age, sex, nor previous therapy were obvious etiologic factors. tET occurred 24.2 +/- 14.4 mo after diagnosis of essential thrombocythemia, and a majority of patients had hepatomegaly and/or splenomegaly, anemia, leukocytosis, and thrombocytopenia. Leukemic cell morphology was myeloblastic and/or monoblastic in 12/12 patients, 5/12 had marrow fibrosis. Despite various treatments, death occurred in 3.6 +/- 2.7 mo; one patient had a brief complete remission.
The megakaryocyte DNA content and platelet formation after the sublethal whole body irradiation of rats
Authors: Tanum G 
Published: October 2019

Abstract
The DNA content of rat bone marrow megakaryocytes (MK) was studied by Feulgen photometry, following whole body irradiation with 2 Gy. The DNA measurements were preceded by acetylcholinesterase staining to avoid missing the smaller 2N-8N MK. The number of 2N-8N MK declined immediately following irradiation, whereas the number of 16N-64N MK remained normal for 4 days before decreasing. The number of 2N-8N and 16N-64N MK reached minimum around days 7 and 10, respectively, and thereafter increased to supranormal values at days 14 and 20, respectively. Platelet production, measured by 35S incorporation into platelets, increased during the first 4 days, then decreased to minimum about day 10. A rise to supranormal values was present at day 20. All values were about normal 30 days after exposure. The observed pattern may be explained as follows: Most of the 16N-64N MK survive the applied dose and maintain their ability to produce platelets. Some of the 2N-4N and 8N MK survive irradiation and transform into platelet-producing MK. No influx of cells from the MK stem cell compartment into the MK compartment can be observed before day 7 after irradiation. One explanation for this time lag may be that thrombocytopenia, which does not occur before then, is an essential stimulus for MK stem cell activation.
Large cell lymphoma complicating acute lymphoblastic leukemia
Authors: Ellerbroek R , Foucar K , Kowal-Vern A , Kemp JD , Kisker T , Tannous R , Strauss R 
Published: October 2019

Abstract
Non-Hodgkin's lymphoma (NHL) is a very rare complication of acute lymphoblastic leukemia (ALL). We present the pathologic, clinical, immunologic, and ultrastructural features of the third reported example of NHL following successfully treated ALL. This white girl developed ALL with predominantly L1 cells at 3.5 yr of age. The lymphoblasts were terminal deoxynucleotidyl transferase (TdT) positive and were non-B, non-T cells. She achieved a complete remission with standard induction therapy and has remained in continuous complete remission. Four and one- third years after the onset of ALL, she developed multifocal, pleomorphic large cell lymphoma of the small bowel, which resulted in episodes of intussusception and obstruction. These pleomorphic and frequently multinucleated lymphoma cells lacked TdT, common ALL antigen, and all tested markers of B cell, T cell, and histiocyte differentiation. Following three small bowel resections, systemic multiagent chemotherapy, and abdominal irradiation, she is currently free of disease.
Liver dysfunction rather than intravascular coagulation as the main cause of low protein C and antithrombin III in acute leukemia
Authors: Rodeghiero F , Mannucci PM , Vigano S , Barbui T , Gugliotta L , Cortellaro M , Dini E 
Published: October 2019

Abstract
Protein C, a newly identified inhibitor of blood coagulation, was measured immunologically in 58 patients with untreated acute leukemias and compared with that of normal subjects. On the average, slightly lower values were found. However, the 17 patients with overt laboratory pictures of decompensated disseminated intravascular coagulation (DIC), including 11 cases with acute promyelocytic leukemia, had protein C concentrations no lower than those of the remaining 41 patients without DIC. Antithrombin III activity and antigen were normal and, like protein C, not lowered in DIC. The concentrations of both proteins were closely correlated with changes in the indexes for liver synthetic function. A subgroup of 13 patients with hyperleukocytic leukemias had lower protein C and antithrombin III, in line with the more compromised synthetic function of their livers. Our findings indicate that liver impairment rather than DIC is the main cause of the changes in the two naturally occurring inhibitors of blood coagulation.
A randomized comparison of postremission therapy in acute myelogenous leukemia: a Southeastern Cancer Study Group trial
Authors: Vogler WR , Winton EF , Gordon DS , Raney MR , Go B , Meyer L 
Published: October 2019

Abstract
The Southeastern Cancer Study Group conducted a post-remission induction randomized trial in adult acute myelogenous leukemia to assess the efficacy of alternate drug therapy during consolidation and of immunotherapy during maintenance. Of 508 evaluable patients entered into the study, 335 (66%) achieved a complete remission treated with a 7-day infusion of cytosine arabinoside at a dose of 100 mg/sq m/day and 3 days of daunorubicin at a dose of 45 mg/sq m/day. Those in remission were randomized to receive 3 courses of 1 of 3 consolidation regimens: (A) a continuous infusion of 5-azacytidine, 150 mg/sq m/day for 5 days; (B) 5-azacytidine plus beta-deoxythioguanosine, 300 mg/sq m/day for 5 days; or (C) cytosine arabinoside, 100 mg/sq m/day intravenously, and thioguanine, 100 mg/sq m orally every 12 hr, plus daunorubicin, 10 mg/sq m every 24 hr daily for 5 days. There was no difference in relapse rate among the 3 arms. Those completing consolidation and remaining in remission were randomized to 1 of 3 maintenance regimens: (D) chemotherapy, 5-day infusion of cytosine arabinoside and 2 days of daunorubicin (same doses as induction) given every 13 wk for 1 yr; (E) BCG given twice weekly for 1 mo and then monthly for 1 yr; or (F) the combination of regimens D and E. The median duration of remission was significantly better on regimen D (17.4 versus 9.4 and 9.5 mo), and median survival was 29 mo compared to 21 mo for the other regimens. Those given different drugs during consolidation than used for induction (regimens A and B) and subsequent chemotherapy for maintenance (regimen D) had the longest remission durations and survival. Immunotherapy was not as good as intensive chemotherapy for maintenance.
A role for sulfhydryl groups in granulocyte aggregation
Authors: Kraut EH , Sagone AL Jr 
Published: October 2019

Abstract
Polymorphonuclear leukocytes (PMN) stimulated by high concentrations of the complement component C5A form cellular aggregates, and both the rate and degree of aggregation are influenced by changes in the PMN plasma membrane and cytoskeleton. Since sulfhydryls are important constituents of the plasma membrane and cytoskeleton, we investigated the effect of agents that oxidize and bind sulfhydryls on C5A-induced aggregation. PMN incubated with diamide, a nonspecific sulfhydryl- oxidizing agent, had a marked increase in their aggregation response to C5A. Tertiary butyl hydroperoxide (BHP), which reacts specifically with the soluble sulfhydryl glutathione (GSH), had no effect on aggregation. The enhancement of PMN aggregation by diamide, but not BHP, suggested that oxidation of non-GSH sulfhydryls contributes to the aggregation response. To test the requirement for sulfhydryls in PMN aggregation, PMN were treated with the sulfhydryl-binding agent N-ethylmaleimide (NEM). NEM markedly impaired aggregation without affecting resting or methylene blue-stimulated [14C]-L-glucose oxidation of the granulocytes. P-chloromercuriphenyl sulfonic acid (PCMPSA), an external sulfhydryl-binding agent, had no effect on aggregation. These studies suggest that cellular sulfhydryls are required for optimal PMN aggregation and that oxidation of these sulfhydryls may be one of the biochemical changes that contributes to aggregation.
Glutathione-dependent protection against oxidative damage of the human red cell membrane
Authors: Fujii S , Dale GL , Beutler E 
Published: October 2019

Abstract
Glutathione (GSH) dependent protection against oxidative damage of human red cell membrane was examined. An artificial system was used in which chloroform/methanol-extracted red cell lipids, in the form of liposomes, were subjected to attack by a peroxidation system consisting of ascorbate-Fe3+. Human erythrocytes contained a nondialyzable factor, completely inactivated by heating in a boiling water bath for 3 min, which showed GSH-dependent inhibition against lipid peroxidation and was devoid of GSH peroxidase activity. On the other hand, GSH-S transferase, highly purified by affinity chromatography, had no inhibitory activity. These findings strongly indicate that the GSH- dependent protection against lipid peroxidation of human red cell membrane is mediated by one or more proteins other than GSH peroxidase and GSH-S transferase.
Hyperleukocytosis and leukostasis: common features of childhood chronic myelogenous leukemia
Authors: Rowe JM , Lichtman MA 
Published: October 2019

Abstract
Ten patients under 20 yr of age with the usual (adult) type of chronic myelogenous leukemia (CML) were seen at the University of Rochester Medical Center from 1970 to 1982. The mean white cell count in these 10 patients at presentation was 360,000/microliter, as compared to a mean of 137,000/microliter in 80 CML patients over 20 yr of age seen during the same time interval (p less than 0.02). Analyses of all 90 cases revealed a significant decrease in the average leukocyte count at presentation with increasing age. The childhood cases also had a significantly higher proportion of blood blasts, promyelocytes, and myelocytes than did the adult subjects (p less than 0.01). Signs of leukostasis were present in 12% of adult cases as compared to 60% of the 10 childhood cases, and in these 6 subjects, the mean white cell count was 510,000/microliter. In these 6 patients, leukapheresis and/or chemical therapy was initiated rapidly, and this was followed by complete resolution of the clinical signs of leukostasis. A review of the literature from 1960 to 1982 identified 61 childhood cases that were reported with the usual type of CML. In this group, the frequency of hyperleukocytosis and the distribution of white cell counts corresponded very closely to the 10 cases studied at the University of Rochester. Thus, the usual type of CML presenting in childhood differs from that of adults in that hyperleukocytosis, blood granulocyte immaturity, and leukostatic central nervous system, retinal, and respiratory signs are significantly more common and extreme and merit rapid cytoreductive treatment.
Micropipette aspiration of human blood platelets: a defect in Bernard- Soulier's syndrome
Authors: White JG , Burris SM , Hasegawa D , Johnson M 
Published: October 2019

Abstract
Previous reports have suggested that platelets from patients with Bernard-Soulier's syndrome (BSS) are not giant cells. Rather, they are normal-sized in suspension, but spread out on glass slides more readily than control cells, yielding the impression of being giant. The present study has used cell sizing techniques, electron microscopy, and micropipette aspiration to evaluate platelets from three patients with BSS. Cell sizing techniques revealed that BSS platelets were considerably larger than normal. The increased size was confirmed in electron microscopic studies of BSS platelets fixed in suspension. However, the BSS platelets did not contain increased amounts of internalized surface membrane considered to be the source of membrane necessary for excessive spreading. A possible explanation for increased spreading of BSS platelets was found in studies of their resistance to deformation in micropipettes. BSS platelets were much less resistant to deformation than normal cells or other abnormal platelets when aspirated under the same negative pressure. Their unusual deformability may explain the tendency of BSS platelets to spread more readily than normal cells on glass slides.
The rare alpha-thalassemia-1 of blacks is a zeta alpha-thalassemia-1 associated with deletion of all alpha- and zeta-globin genes
Authors: Felice AE , Cleek MP , McKie K , McKie V , Huisman TH 
Published: October 2019

Abstract
Restriction endonuclease mapping with alpha and zeta-globin gene probes showed differences between the alpha-thalassemia-1 (alpha-thal-1) condition in two patients with HbH disease. One patient had the rare black type of alpha-thal-1 together with alpha-thal-2 and HbS heterozygosities. The second patient was a Laotian child with HbE, Hb Constant Spring (alpha-thal-2), and alpha-thal-1 heterozygosities. The diagnoses were based on clinical, hematologic, and biochemical data. Whereas DNA fragments hybridizing to a zeta-probe were obtained from the Laotian type of alpha-thal-1, neither alpha nor zeta-gene fragments could be identified deriving from the black type of alpha-thal-1. Therefore, the black type of alpha-thal-1 is associated with a deletion of the entire zeta 2-psi zeta-psi alpha-alpha 2-alpha 1 gene complex and can be considered a zeta alpha-thal-1. It is likely that homozygosity for such a condition will lead to embryonic wastage, explaining the absence of hydrops fetalis in blacks.
Platelet size and age determine platelet function independently
Authors: Thompson CB , Jakubowski JA , Quinn PG , Deykin D , Valeri CR 
Published: October 2019

Abstract
This study was undertaken to examine the interaction of platelet size and age in determining in vitro platelet function. Baboon megakaryocytes were labeled in vivo by the injection of 75Se- methionine. Blood was collected when the label was predominantly associated with younger platelets (day 2) and with older platelets (day 9). Size-dependent platelet subpopulations were prepared on both days by counterflow centrifugation. The reactivity of each platelet subpopulation was determined on both days by measuring thrombin-induced aggregation. Platelets were fixed after partial aggregation had occurred by the addition of EDTA/formalin. After removal of the aggregated platelets by differential centrifugation, the supernatant medium was assayed for remaining platelets and 75Se radioactivity. Comparing day 2 and day 9, no significant difference was seen in the rate of aggregation of a given subpopulation. However, aggregation was more rapid in the larger platelet fractions than in the smaller ones on both days. A greater percentage of the 75Se radioactivity appeared in the platelet aggregates on day 2 than on day 9. This effect was independent of platelet size, as it occurred to a similar extent in the unfractionated platelets and in each of the size-dependent platelet subpopulations. The data indicate that young platelets are more active than older platelets. This study demonstrates that size and age are both determinants of platelet function, but by independent mechanisms.
Monoclonal antibodies detecting antigenic determinants with restricted expression on erythroid cells: from the erythroid committed progenitor level to the mature erythroblast
Authors: Yokochi T , Brice M , Rabinovitch PS , Papayannopoulou T , Stamatoyannopoulos G 
Published: October 2019

Abstract
Two new cell surface antigens specific for the erythroid lineage were defined with cytotoxic IgM monoclonal antibodies (McAb) (EP-1; EP-2) that were produced using BFU-E-derived colonies as immunogens. These two antigens are expressed on in vivo and in vitro derived adult and fetal erythroblasts, but not on erythrocytes. They are not detectable on resting lymphocytes, concanavalin-A (Con-A) activated lymphoblasts, granulocytes, and monocytes or granulocytic cells or macrophages present in peripheral blood or harvested from CFU-GM cultures. Cell line and tissue distributions distinguish McAb EP-1 and EP-2 from all previously described monoclonal antibodies. McAb EP-1 (for erythropoietic antigen-1) inhibits the formation of BFU-E and CFU-E, but not CFU-GM, colonies in complement-dependent cytotoxicity assays. By cell sorting analysis, about 90% of erythroid progenitors (CFU-E, BFU-E) were recovered in the antigen-positive fraction. Seven percent of the cells in this fraction were progenitors (versus 0.1% in the negative fraction). The expression of EP-1 antigen is greatly enhanced in K562 cells, using inducers of hemoglobin synthesis. McAb EP-2 fails to inhibit BFU-E and CFU-E colony formation in complement-dependent cytotoxicity assays. EP-2 antigen is predominantly expressed on in vitro derived immature erythroblasts, and it is weakly expressed on mature erythroblasts. The findings with McAb EP-1 provide evidence that erythroid progenitors (BFU-E and CFU-E) express determinants that fail to be expressed on other progenitor cells and hence appear to be unique to the erythroid lineage. McAb EP-1 and EP-2 are potentially useful for studies of erythroid differentiation and progenitor cell isolation.
Characterization of 25 monoclonal antibodies to factor VIII-von Willebrand factor: relationship between ristocetin-induced platelet aggregation and platelet adherence to subendothelium
Authors: Stel HV , Sakariassen KS , Scholte BJ , Veerman EC , van der Kwast TH , de Groot PG , Sixma JJ , van Mourik JA 
Published: October 2019

Abstract
We have studied the role of factor VIII-von Willebrand factor (FVIII- vWF) in both platelet adherence to subendothelium and ristocetin- induced platelet aggregation using monoclonal antibodies to human FVIII- vWF. Twenty-five monoclonal antibodies were obtained, two of which were directed to the factor VIII moiety of FVIII-vWF; one of these two completely inhibited the procoagulant activity (FVIII:C). The remaining 23 monoclonal antibodies were directed to the von Willebrand factor moiety of FVIII-vWF. The ability of the latter monoclonal antibodies to inhibit platelet adherence to arterial subendothelium was investigated with a perfusion model. According to the number of platelets adhering to the subendothelium, three groups of monoclonal antibodies could be discerned: (A) antibodies not affecting platelet adherence; (B) antibodies that inhibited platelet adherence to the level as observed when von Willebrand's disease plasma was tested; and (C) antibodies that completely inhibited both platelet adherence to subendothelium and ristocetin-induced platelet aggregation. The two antibodies present in group C competed for the same or closely related epitope(s) present on FVIII-vWF. These results demonstrate that a domain is present on the FVIII-vWF molecule that is associated both with ristocetin-induced aggregation and with the ability of FVIII-vWF to support platelet adherence to the subendothelium. Based on these observations, it is concluded that ristocetin-induced binding of FVIII-vWF to platelets reflects, at least in part, a physiologic mechanism regulating the function of FVIII-vWF in primary hemostasis.
T lymphocyte colony assay in hemophiliacs
Authors: Ragni MV , Winkelstein A , Evans TL , Lewis JH , Bontempo FA , Spero JA , Rabin BS 
Published: October 2019

Abstract
Unexplained lymphadenopathy, with or without accompanying symptoms, known as the “lymphadenopathy syndrome,” has been recognized in groups at risk for acquired immune deficiency syndrome (AIDS), namely, homosexuals and hemophiliacs. To date, however, no test has been defined that discriminates between asymptomatic individuals and those with adenopathy in these high-risk groups. The T colony assay, which measures T lymphocyte growth in soft agar and which allows selective T cell proliferation with minimal cell-cell contact, was evaluated in asymptomatic hemophiliacs. Significantly lower mean colony counts were found in eight hemophiliacs with adenopathy (HA), 763 +/- 348 (+/- SEM), than in 16 healthy hemophiliacs (HH) 3,044 +/- 661 (P less than .005), or than in 24 heterosexual control subjects, 3,964 +/- 395 (P less than .005). The in vitro addition of exogenous interleukin-2 (IL- 2) restored normal colony growth in the HA population. These results indicate that the T colony assay can detect abnormal cell-mediated immunity among hemophiliacs and specifically discriminates between asymptomatic hemophiliacs (HH) and those with adenopathy (HA). In addition, IL-2 may be of potential benefit in improving T cell defects in AIDS or the “lymphadenopathy syndrome”; however, this remains to be proven.