bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of a microtubule stabilizing agent on the response of platelets to vincristine
Authors: White JG , Rao GH 
Published: October 2019

Abstract
The discoid shape of blood platelets is supported by a circumferential bundle of microtubules. Removal of the microtubules by an antimitotic drug, vincristine, is associated with loss of lentiform appearance, formation of tubulin paracrystals, a depressed response to aggregating agents, and impaired secretory activity. Recent studies have suggested that the action of vincristine on platelet secretion and aggregation is directly related to its action on microtubules, while other work had indicated that the antimitotic drug prevents the release reaction by inhibiting prostaglandin synthesis. The present study has examined the influence of taxol, a microtubule stabilizing agent, on the response of platelets to vincristine. Taxol completely prevented vincristine- induced shape change, microtubule disassembly, and tubulin paracrystal formation, even at concentrations one-tenth that of the antimitotic drug. Pretreatment with vincristine to dissociate microtubules and convert tubulin to crystals before exposure to taxol did not affect altered shape or tubulin paracrystals, but did cause assembly of free pools of tubulin into tubular polymers. Studies of physiology confirmed that vincristine, in amounts that remove microtubules, depresses platelet aggregation and secretion, effects that could be overcome by increasing agonist concentration. Although completely preventing microtubule dissociation, taxol had no corrective influence on vincristine-induced inhibition of platelet function. Biochemical studies revealed that vincristine concentrations that disassembled microtubules and blocked secretion did not inhibit conversion of 14C- arachidonic acid to thromboxane B2. The findings suggest that vincristine inhibits platelet function through some mechanism other than disassembling microtubules, but the other mechanism does not involve inhibition of prostaglandin synthesis.
Partial purification and characterization of a growth factor for macrophage progenitor cells with high proliferative potential in mouse bone marrow
Authors: Kriegler AB , Bradley TR , Januszewicz E , Hodgson GS , Elms EF 
Published: October 2019

Abstract
A population of macrophage progenitor cells, with high proliferative potential, has recently been demonstrated in postfluorouracil-treated and normal mouse bone marrow (BM) in vitro, when the newly discovered growth factor (synergistic activity, SA) is combined with a macrophage colony-stimulating factor (CSF) as a proliferative stimulus. SA, shown to be present in human spleen and placental conditioned media (HSCM and HPCM, respectively) have been studied and found to be unstable to trypsin digestion and to heating at 50 degrees C or above; stable between pH 4 and 9; nonadherent to Con-A-Sepharose; and to have an isoelectric point between pH 5 and 5.8 and a molecular weight of between 14,000 and 21,000 as indicated by gel filtration chromatography. SAs from both HSCM and HPCM have been purified 89- and 122-fold, respectively, by precipitation of extraneous proteins at pH 5 followed by chromatographing twice on Sephacryl S200. Neither of these partially purified SAs contain any CSF for mouse BM. These results indicate that the SAs from HSCM and HPCM may be closely related and that they are structurally different from CSFs derived from various murine sources that have been shown to be stable to proteolytic enzymes and heat.
Clinical staging system for hairy-cell leukemia
Authors: Jansen J , Hermans J 
Published: October 2019

Abstract
To find a clinical staging system for patients with hairy cell leukemia, 391 patients contributed by 22 centers were analyzed using the proportional hazard survival model. Attention was paid to nonsplenectomized patients to find a staging system to predict the survival length at the time of diagnosis. On the basis of hemoglobin level and spleen size at the time of diagnosis, 3 stages could be distinguished with significantly different prognoses (stages I-III). In addition, we addressed the question of splenectomy to identify those patients who benefit from the operation. Using arbitrary, but clinically relevant, criteria to call the operation beneficial, splenectomy appears to be indicated for patients with large spleens (greater than or equal to 4 cm under costal margin) or with smaller, but palpable, spleens when anemia (Hb less than 12 g/dl) is present. The third question concerned the splenectomized patients. To indicate the patients who have a poor postsplenectomy survival, a staging system was developed on the basis of hemoglobin level and number of neutrophils at 2–3 mo after the operation (stages A-C). The validity of the two staging systems was supported by the results of an analysis of an independent test series of patients. These staging systems may be helpful for the choice of therapy and in the planning of clinical trials in patients with hairy-cell leukemia.
Adolescent and adult acute lymphoblastic leukemia: prognostic features and outcome of therapy. A study of 293 patients
Authors: Baccarani M , Corbelli G , Amadori S , Drenthe-Schonk A , Willemze R , Meloni G , Cardozo PL , Haanen C , Mandelli F , Tura S 
Published: October 2019

Abstract
The case histories of 293 adolescent and adult patients with acute lymphoblastic leukemia (ALL) first seen and treated between 1969 and 1979 are reviewed. A complete remission (CR) was achieved in 79% of cases. Male sex, advanced age (greater than or equal to 30 yr old), and early CNS involvement were the major determinants of remission failure. Median duration of first CR was 16 mo, with 23 patients (actuarial proportion 25%) alive and relapse-free at 5 yr. The major determinant of first CR length was white blood cell (WBC) count (best cut-off value at 35 X 10(9)/liter). First CR length was also negatively affected by early CNS involvement, morphological FAB L3 subtype, and B-cell (Smlg+) leukemia, but these features were significantly associated with a high WBC count. First CR length in patients 11–15 yr old did not differ significantly from that of patients 16–59 yr old. The negative prognostic value of T-cell (E+) leukemia was not confirmed in this adult series. CNS prophylaxis provided an effective protection against CNS relapse. Maintenance chemotherapy was apparently more effective when 4 or more than 4 drugs were employed. “Low risk” patients (WBC count less than 35 X 10(9)/liter still relapsed rather frequently (32% at 1 yr, 49% at 2 yr), with 33% of them alive and relapse-free at 5 yr. “High risk” patients (WBC count greater than or equal to 35 X 10(9)/liter +/- early CNS involvement +/- morphological L3 subtype +/- B-cell leukemia) relapsed very quickly (50% at 6 mo. 70% at 1 yr), with only 6% of them relapse-free at 5 yr.
Analysis of late infections after human bone marrow transplantation: role of genotypic nonidentity between marrow donor and recipient and of nonspecific suppressor cells in patients with chronic graft-versus-host disease
Authors: Atkinson K , Farewell V , Storb R , Tsoi MS , Sullivan KM , Witherspoon RP , Fefer A , Clift R , Goodell B , Thomas ED 
Published: October 2019

Abstract
Infections occurring 6 mo or later after bone marrow transplantation for severe aplastic anemia or hematologic malignancy were analyzed in 98 long-term survivors. Varicella-zoster (VZ) infections were analyzed separately from all other infections. The factor predisposing most strongly to late VZ infection was genotypic nonidentity for HLA between marrow donor and recipient. There was a suggestion that chronic graft- versus-host disease (GVHD) associated with the presence of nonspecific suppressor cells also predisposed to late VZ infection, while age less than 10 yr was protective against such infections. Chronic GVHD predisposed to late non-VZ infections, but this was not increased by the presence of nonspecific suppressor cells. HLA nonidentify between patient and marrow donor further increased the risk of late non-VZ infections over and above that due to the presence of chronic GVHD. Receipt of a syngeneic transplant appeared protective for late non-VZ infections. These findings suggest that full genotypic identity for HLA between donor and recipient may be required for optimal immune reconstitution after marrow transplantation and may denote a possible biologic role for nonspecific suppressor T cells in humans.
Immunologic and clinical effects of repeated blood exchange in familial erythrophagocytic lymphohistiocytosis
Authors: Ladisch S , Ho W , Matheson D , Pilkington R , Hartman G 
Published: October 2019

Abstract
Depressed cellular immune function and increased susceptibility to infection characterize familial erythrophagocytic lymphohistiocytosis (FEL), a usually fatal autosomal recessive disease. One component of the immunodeficiency is plasma-mediated inhibition of lymphocyte proliferation. We have tested whether repeated plasma or blood exchange would decrease plasma inhibitory activity and improve cellular immune function in FEL. Following this treatment, reduction in plasma inhibitory activity, reversal of depressed antigen-specific lymphocyte proliferative responses and monocyte antibody-dependent cytotoxic function in vitro, and clinical improvement were complete in two and partial in one of three patients studied. Relapse, which was ultimately fatal, was associated with recurrence of the immune defects. These findings suggest that cellular immunodeficiency in FEL is acquired and possibly related to circulating immunosuppressive activity, the removal of which is associated with transient immunologic and clinical recovery.
Karyotypic polymorphism in acute myelofibrosis
Authors: Shah I , Mayeda K , Koppitch F , Mahmood S , Nemitz B 
Published: October 2019

Abstract
Acute myelofibrosis (AMF) was diagnosed in a 59-yr-old black male in September 1978, on the basis of pancytopenia, lack of hepatosplenomegaly, fibrosis of the marrow, and paucity of teardrop red blood cells in the peripheral blood. Since then the patient has demonstrated an unusually long survival of 36 mo with a changing cytogenetic course. His initial 46, XY normal karyotype changed in 20 mo to trisomy 8, followed 1 yr later by 1:4 translocation in peripheral blood. Simultaneously with these changes, the fibrosis in the bone marrow progressively decreased, ultimately terminating in chronic granulocytic leukemia-like presentation with reversal to 46, XY karyotype. Fibroblast culture failed to show any evidence of cytogenetic abnormalities. The disappearance of fibrosis confirmed by trichrome and reticulin stains and lack of cytogenetic abnormalities in fibroblasts confirms the secondary role of fibrosis.
Glycogenolysis versus glucose transport in human granulocytes: differential activation in phagocytosis and chemotaxis
Authors: Weisdorf DJ , Craddock PR , Jacob HS 
Published: October 2019

Abstract
Granulocytes depend primarily on anaerobic glycolysis to supply the necessary energy for locomotion and chemotaxis. Either transmembrane transport of extracellular glucose or catabolism of intracellular glucose can supply glycolytic substrate. In this report, using enzymatic analysis of granulocyte glycogen, we describe conditional requirements for glycogenolysis, namely phagocytosis. With abundant extracellular glucose, granulocyte glycogen content (12.2 +/- 1.6 micrograms/10(6) cells) is not depleted whether or not incubations include various soluble chemotaxins (e.g., FMLP, C5ades arg, arachidonic acid). These chemotaxins accelerate transmembrane glucose uptake. With near complete absence (less than 6 mg/dl) of extracellular glucose, both resting and chemotaxin (FMLP, C5ades arg, arachidonic acid) stimulated granulocytes catabolize significant endogenous glycogen. Phagocytosis, however, fails to enhance glucose uptake and promotes glycogen consumption even with abundant extracellular glucose. Simple particle-phagocyte attachment without internalization (produced by cytochalasin-B) also promoted glycogen consumption, suggesting that this membrane deformation alone is a sufficient trigger for glycogenolysis. Resting or chemotactic granulocytes, therefore, can adapt their energy source pending extracellular glucose availability-- often compromised at inflammatory sites-while phagocytic cells depend primarily, if not exclusively, on endogenous glycogen stores. This differential metabolic activation defends the granulocytes energy supply and may be critical in supporting antimicrobial activity in acute inflammation.
Evidence for interaction between platelet fibrinogen receptors
Authors: Peerschke EI 
Published: October 2019

Abstract
Previous analysis of fibrinogen binding to human aspirin-treated gel- filtered platelets yielded upwardly concave Scatchard plots. To ascertain whether this was due to the presence of independent heterogeneous receptor populations binding fibrinogen with different affinities, the dissociation of purified 125I-fibrinogen from ADP- treated gel-filtered platelets was evaluated as a function of receptor occupancy. Dissociation of bound labeled fibrinogen was measured after 50-fold dilution with buffer containing O, 0.2, 0.8, and 2.0 mg/ml unlabeled fibrinogen. Dissociation of labeled fibrinogen increased with increasing receptor occupancy and was biphasic. With buffer alone, 76.0% +/- 5.8% (SD) of labeled fibrinogen dissociated in 30 min, with an initial rate of 0.392 +/- 0.175 min-1; with 0.2 mg/ml fibrinogen, 83.7% +/- 3.9% dissociated, with an initial rate of 0.589 +/- 0.044 min- 1; with 0.8 mg/ml, 91.8% +/- 1.3% of the labeled fibrinogen dissociated, with an initial rate of 0.910 +/- 0.028 min-1; and with 2.0 mg/ml fibrinogen, 97.3% +/- 2.3% of label dissociated, with an initial rate of 1.06 +/- 0.257 min-1 (n=5). The final rates of fibrinogen dissociation were unaffected by unlabeled fibrinogen in the dilution buffer and were not statistically different from the final dissociation rate of 0.015 +/- 0.10 min-1 observed following dilution with buffer alone. These results were neither an artifact of aspirin treatment or gel filtration, as similar observations were made using non-aspirin-treated washed platelets, nor were they an artifact of the purified fibrinogen preparations, because binding studies using whole plasma as the major source of fibrinogen also yielded upwardly concave Scatchard plots. Since the data demonstrate that the initial rate and extent of fibrinogen dissociation are dependent on fibrinogen receptor occupancy, they suggest receptor interactions possibly resulting from receptor clustering or crosslinking. Because the dissociation was biphasic, the results also suggest some heterogeneity among platelet- fibrinogen interactions.
Biochemical correlates of the differential sensitivity of subtypes of human leukemia to deoxyadenosine and deoxycoformycin
Authors: Matsumoto SS , Yu AL , Bleeker LC , Bakay B , Kung FH , Nyhan WL 
Published: October 2019

Abstract
Leukemic cells incubated in vitro with 2′-deoxyadenosine (dAdo) plus an inhibitor of adenosine deaminase, 2′-deoxy-coformycin (DCF), show different metabolic responses depending on the histologic and immunologic type of the leukemia. Leukemic cells were obtained from 54 patients with acute lymphoblastic leukemia (ALL), 9 with myeloid or nonlymphoblastic leukemia, 3 with chronic lymphocytic leukemia (CLL), and 3 with lymphoma. There was a wide variation in the LD50, the concentration of dAdo that caused 50% inhibition of the incorporation of 3H-thymidine into cells in the presence of 20 microM DCF. T-cell leukemia specimens were much more sensitive to dAdo than were specimens of pre-B-ALL and null-ALL. In leukemic cells that had been incubated with 14C-dAdo plus DCF, a good correlation was observed between the LD50 and the ratio of 14C-deoxyATP to ATP (correlation coefficient for the fit to a hyperbola = 0.853). The accumulation of deoxyATP by the leukemic cell specimens was correlated best with the activity of ecto- ATPase, less well with cytoplasmic 5′-nucleotidase and deoxyadenosine kinase, and poorly with adenosine deaminase and ecto-5′-nucleotidase. The clinical response to DCF therapy of a patient with T-ALL and another with pre-B-ALL was consistent with the in vitro metabolic response of their cells to DCF and dAdo.
Multimeric structure of platelet factor VIII/von Willebrand factor: the presence of larger multimers and their reassociation with thrombin- stimulated platelets
Authors: Fernandez MF , Ginsberg MH , Ruggeri ZM , Batlle FJ , Zimmerman TS 
Published: October 2019

Abstract
The multimeric structure of platelet factor VIII/von Willebrand factor (FVIII/vWF) in cell extracts and in collagen and thrombin releasates has been analyzed by SDS polyacrylamide gel electrophoresis followed by detection with 125I-anti-FVIII/vWF. Platelets contained larger multimers than those normally present in plasma. When secreted FVIII/vWF was analyzed, all platelets. In contrast, in thrombin releasates the larger multimers were lost in a manner dependent on divalent cations, time, and thrombin dose. This loss could not be accounted for by modification of FVIII/vWF by thrombin or platelet enzymes since no effect of thrombin on the multimeric structure of FVIII/vWF in the absence of platelets or in the presence of platelet lysates was observed. Large multimers of 125I-labeled purified FVIII/vWF underwent divalent cation-dependent association with platelets in the presence of thrombin, indicating that the loss of FVIII/vWF from thrombin releasates was due to reassociation with the platelet. These studies show a structural difference between platelet and plasma FVIII/vWF that suggests a specific role for platelet FVIII/vWF in hemostasis.
Acute leukemia associated with the t(4;11) chromosome rearrangement: ultrastructural and immunologic characteristics
Authors: Parkin JL , Arthur DC , Abramson CS , McKenna RW , Kersey JH , Heideman RL , Brunning RD 
Published: October 2019

Abstract
The acute leukemia associated with the t(4;11) chromosome rearrangement is characterized by relatively consistent clinical features: occurrence primarily in young individuals, hyperleukocytosis, and poor response to therapy. This study describes the morphological, ultrastructural, and immunologic characteristics of the leukemic cells from ten patients with this type of leukemia. The morphological features of the leukemic blasts vary from lymphoid-appearing to monocytic. Ultrastructurally and cytochemically, some of the lymphoid-appearing blasts possess features of myeloid origin. The immunologic phenotype is characteristically E- SIg- CALLA- BA-1- BA-2+ HLA-DR+ and TdT+. These findings suggest that the t(4;11)-associated acute leukemia represents a proliferation of an early myeloid progenitor cell.
Adipocyte development and the loss of erythropoietic capacity in the bone marrow of mice after sustained hypertransfusion
Authors: Brookoff D , Weiss L 
Published: October 2019

Abstract
In this electron microscopic study, erythropoiesis in mice was completely suppressed by repeated hypertransfusion for up to 6 wk. We describe a sequence of ultrastructural changes in the marrow's stromal cells that accompany the resulting shift from erythropoietic to granulopoietic tissue. These include the destruction of medullary macrophages, the accelerated development of marrow adipocytes and reticular cells, and a reduction in the amount of vascular space in the marrow. The absence of macrophages was highlighted by the complete lack of erythrophagocytosis in the marrows of hypertransfused mice that were injected with the hemolysing agent, phenylhydrazine. The changes in the marrow stroma probably underlie the shift in the marrow's hematopoietic microenvironment. Repeated phlebotomy of mice that had been hypertransfused for 2 wk evoked the appearance of unique stromal cells in the marrow, similar to cells that have been associated with accelerated erythropoiesis. The newly anemic mice were otherwise unable to mount an erythropoietic response to repeated bleeding, showing that the decline in the erythropoietic microenvironment brought on by sustained hypertransfusion was a lasting one.
A quantitative method to measure human platelet chemotaxis using indium- 111-oxine-labeled gel-filtered platelets
Authors: Lowenhaupt RW , Silberstein EB , Sperling MI , Mayfield G 
Published: October 2019

Abstract
Human blood platelets have been shown to migrate directionally and specifically toward collagen in plasma in vitro. We have developed a new system to monitor this behavior using a linear 7-compartment chamber with 111In-oxine-labeled gel-filtered platelets. The compartments are separated by various Nuclepore and Millipore filter membranes. Radiolabeled platelets suspended in plasma are placed in the central compartment and the other compartments are filled with platelet- free plasma. When collagen is added to an end compartment, platelets migrate toward that end. The degree of this directed movement or chemotaxis can be measured by counting the radioactivity of the contents of each compartment and then comparing the counts from radiolabeled platelets that have moved to the end that holds the chemotactic inducer with those that have randomly migrated to the opposite end, containing only plasma. This assay system allows quantitative comparisons between the chemotaxis-inducing abilities of different substances and permits the study of soluble materials. Experiments to determine the optimal conditions for the procedure are reported, and the advantages of this new method for the investigation of platelet chemotaxis and the identification of chemotaxins are discussed.
Expression of a myeloid marker on TdT-positive acute lymphocytic leukemic cells: evidence by double-fluorescence staining
Authors: Bettelheim P , Paietta E , Majdic O , Gadner H , Schwarzmeier J , Knapp W 
Published: October 2019

Abstract
The expression of a myeloid-specific antigen was detected on TdT- positive blast cell populations in two cases of childhood acute lymphocytic leukemia. Double-fluorescence staining by using the monoclonal antibody, VIM-D5, which is specific for cells of myeloid origin, in combination with TdT antiserum revealed that a distinct portion of the blast cells carried both markers. The finding represents the first direct demonstration of this specific biphenotype in leukemic cells and was interpreted as the abnormal expression of a myeloid antigen on lymphoid blast cells.
Childhood lymphoblastic leukemia with natural killer activity: establishment of the leukemia cell lines retaining the activity
Authors: Komiyama A , Kawai H , Miyagawa Y , Akabane T 
Published: October 2019

Abstract
Leukemic cells from a child with acute lymphoblastic leukemia (ALL) had high natural killer (NK) activity against K562 as determined by the 51Cr release assay at a 40:1 effector:target ratio: percent lysis was 76.8% (147.4% of normal lymphocyte value) and higher than that of control leukemic cells from 12 childhood ALL (0.1% +/- 0.3%). Two leukemic cell lines (SPI-801 and SPI-802) were established from the patient, and they were essentially the same as the freshly harvested leukemic cells in their morphology, cytochemistry, immunologic markers, and functions. The cultured cell lines as well as the fresh leukemic cells had receptors for sheep red blood cells, IgG-Fc, and C3. The cultured cells were OKM1+, Ia+ and asialo-GM1+, and were OKT-3-, OKT-4- , OKT-6-, OKT-8-, Leu-7-, human monocyte-, common ALL-, T cell-, surface Ig-, and cytoplasmic IgM- as determined by the immunofluorescence method. The two cell lines shared the same chromosome abnormalities. Their chromosomes were in hypotriploid region (63--73), and 6q-, 11p+, and several marker chromosomes were demonstrated. They had spontaneous cytotoxicity against K562 (percent lysis: up to 17.8% and 33.5% of normal lymphocyte value in SPI-801 and SPI-802, respectively) and Molt-3 (38.2% and 27.8% of normal lymphocyte value), but not against Raji and mitogen-induced normal lymphoblasts. Such phenotypic and functional characteristics of the fresh leukemic cells and cultured cells are virtually identical to those of NK cells, demonstrating a new phenotype of childhood ALL of NK cell origin.