bluuebunny/crossref_metadata_2025_split huggingface dataset:
The agglutination of human platelets by botrocetin: evidence that botrocetin and ristocetin act at different sites on the factor VIII molecule and platelet membrane
Authors: Howard Margaret A. , Perkin Jean , Salem Hatem H. , Firkin B. G. 
Published: March 2008

Summary. Botrocetin caused a factor VIII (FVIII) dependent platelet agglutination which was associated with a reduction in the plasma levels of all FVIII parameters as a result of specific binding of FVIII to the platelets. The site of binding of FVIII to the platelet in response to ristocetin or botrocetin involves the glycoprotein 1 complex.This is suggested by the inability of chymotrypsin treated platelets or platelets from patients with the Bernard‐Soulier syndrome to agglutinate in response to ristocetin.These platelets responded to botrocetin, but this was greatly reduced compared to normal. Crossed immunoelectrophoretic analysis indicated that in the presence of botrocetin most multimetric forms of FVIII bound to the platelet, whereas ristocetin caused binding of high and intermediate molecular weight forms. The antibiotic vancomycin inhibited platelet agglutination by ristocetin but had no effect on that caused by botrocetin. Assays of FVIII von Willebrand factor (VIII:vWf) using botrocetin compared well with those obtained using ristocetin in plasmas from normal individuals and from patients with classical von Willebrand disease (vWd).However, a patient with variant vWd demonstrated 100% botrocetin cofactor activity and 0% ristocetin cofactor activity. This suggested that the site of interaction on the FVIII molecule for botrocetin and ristocetin are different. Therefore the diagnosis of some von Willebrand variants cannot be excluded on the basis of a normal botrocetin cofactor assay.
Book Reviews
Authors: Catovsky Daniel , Turner M. W. , Gunson H. H. , Hoffbrand A. V. 
Published: March 2008

Functional T Cell Subsets Defined by Monoclonal Antibodies. Immunological Reviews, Vol. 74 (Edited by G. Möller).Primary and Secondary Immunodeficiency Disorders. Edited by R. K. Chandra.Progress in Clinical and Biological Research. Volume 108. Massive Transfusion in Surgery and Trauma. Edited by J. Collins, K. Murawski and A.W. Shafer.The Cobalamins. Edited by Charles A. Hall.
The effect of platelet factor 4 (PF4) on assays of plasma heparin
Authors: Levine Shirley P. , Sorenson Richard R. , Harris Margaret A. , Knieriem Linda K. 
Published: March 2008

Summary.Platelet factor 4 (PF4) is a potent antiheparinin vitro. In view of the large amount of PF4 secreted from platelet α‐granules during routine blood collection and processing techniques, the potential significance of this release was investigated using three measurements of heparin activity: the activated partial thromboplastin time (aPTT), the thrombin time, and factor Xa inactivation using the chromogenic substrate S2222 for assay of factor Xa. The results demonstrate that purified PF4 neutralizes heparin activity when added in increasing amounts to normal platelet‐poor plasma containing a fixed concentration of commercial porcine gut mucosal heparin. This effect was seen when assaying heparin activity by all three methods. In addition, when heparin was added in increasing concentrations to pooled plasma samples that were collected from normal volunteers, there was neutralization of heparin activity in blood samples collected by routine citrate anticoagulation (CIT60) in comparison to blood samples collected simultaneously with platelet secretion inhibiting agents added to the anticoagulant (CIT+). This effect was seen when assaying heparin by the aPTT and thrombin time. These data confirm that both purified and secreted PF4 have significant antiheparin activity when heparin is addedin vitroto normal plasma.Neutralization of circulating heparin by PF4 secreted during blood collection from anticoagulated patients could result in underestimation of the actualin vivoheparin concentration. In order to evaluate the significance of this effect, purified PF4 was added to plasma collected from heparinized patients and again PF4 neutralized heparin activity. This was seen, however, only when heparin activity was measured by the thrombin time or Xa inactivation assays. There was minimal shortening of the aPTT when PF4 was added in final concentrations up to 1000 ng/ml. When blood samples were simultaneously collected from anticoagulated
The effect of low dose Ara‐C in acute non‐lymphoblastic leukaemias and atypical leukaemia
Authors: Ishikura Hiroto , Sawada Hiroyoshi , Okazaki Toshiro , Mochizuki Toshihiro , Izumi Yoichiro , Yamagishi Morihisa , Uchino Haruto 
Published: March 2008

SUMMARYNine patients with nonlymphocytic leukaemia and one patient with refractory anaemia with excess of blasts (RAEB) were treated subcutaneously with Ara‐C at a low dose of 10 mg/m2/12 h; complete remission was obtained in seven patients. In all cases severe pancytopenia was observed during treatment. We measured the concentration of Ara‐C in serum, and found that the maximum concentration reached a peak (52‐132 ng/ml; mean 84‐2 ng/ml) at 15 min following injection. These concentrations can be considered sufficient to inhibit DNA synthesis. Primary short‐term culture of human leukaemic cells with low dose Ara‐C was also performed, and differentiation of leukaemic cells was observed for several types of leukaemic cells. The in vitro findings corresponded to the observed clinical effects. From the above results, the action of low dose Ara‐C may have resulted from a combination of two different mechanisms, its cytostatic effect and its differentiation‐inducing effect.
Prediction of response of acute nonlymphocytic leukaemia to therapy with ‘high dose’ cytosine arabinoside
Authors: Preisler H. D. , Epstein J. , Barcos M. , Priore R. , Raza A. , Browman G. P. , Vogler R. , Winton E. , Grunwald H. , Rai K. , Brennan J. , Bennett J. , Goldberg J. , Gottlieb A. , Chervenick P. , Joyce R. , Miller K. , Larson R. , D'Arrigo P. , Doeblin T. , Stein M. , Bloom M. , Steele R. , Lee H. 
Published: March 2008

SummaryThe Leukemia Intergroup Study has treated 110 patients with acute nonlymphocytic leukaemia with ‘high dose’ cytosine arabinoside remission induction therapy and studied the factors which were related to the outcome of therapy. With respect to death during remission induction therapy, only patient age was of prognostic significance. Treatment failure due to resistant leukaemia was associated with a high pretherapy leukaemic cell mass, the presence of few cells in S phase, and insensitivity of DNA synthesis to cytosine arabinoside. If, after 6 d of therapy, more than 40% of the marrow cells were leukaemic, the patient almost invariably failed to enter complete remission because of persistent leukaemia. Simultaneous consideration of the pretherapy labelling index and the per cent abnormal cells in the day 6 marrow permitted a distinction to be made between almost all patients who would enter remission or fail therapy because of persistent leukaemia.
Sequential karyotypic evolutions and bone marrow aplasia preceding acute myelomonocytic transformation from myelodysplastic syndrome
Authors: Tomonaga M. , Tomonaga Y. , Kusano M. , Ichimaru M. 
Published: March 2008

SUMMARYSerial haematopathological and cytogenetic studies disclosed three distinct clinical phases in a case of refractory anaemia (RA), a subtype of myelodysplastic syndrome (MDS; FAB group, 1982): first, chronic MDS phase (1 year 10 months) with karyotypic abnormality (45, XY, –7) (Clone I); second, hypo‐aplastic phase concurrent with first clonal evolution (45, XY, –7, 12p –) (Clone II); third, acute myelomonocytic leukaemia phase (6 months) with second clonal evolution (45, XY, ‐ 7, t (lq‐; Bq +), Bq ‐, 12p ‐) (Clone III). In the second phase the bone marrow became almost aplastic as Clone II expanded progressively, indicating simultaneous occurrence in Clone II stem cells of growth advantage for self‐renewal function over Clone I and normal stem cells, and arrest of differentiation. These observations support the hypothesis that leukaemic change in MDS, at least in RA, occurs by stepwise clonal evolution(s), not by progressive arrest of differentiation in original MDS clone.
The severity of immune neutropenia correlates with the maturational specificity of antineutrophil antibodies
Authors: Harmon David C. , Weitzman Sigmund A. , Stossel Thomas P. 
Published: March 2008

SUMMARYSera from 15 patients with antineutrophil antibodies against peripheral blood neutrophils were incubated with normal bone marrow, and the reaction with marrow precursors was determined. Serum from controls did not deposit IgG on either peripheral blood or marrow myeloid cells. Serum from patients with moderate immune neutropenia with myeloid hyperplasia deposited IgG on neutrophils, bands and metamyelocytes, but not on earlier precursors. Serum from one patient with severe neutropenia and myeloid hypoplasia deposited IgG on myelocytes and promyelocytes as well as more mature cells. Serum from a patient with antineutrophil antibodies which impaired chemotaxis but who did not have neutropenia deposited IgG only on neutrophils and occasional bands. Immune neutropenia may become increasingly severe as antibodies become directed against earlier precursors.
Low dose cytosine arabinoside (Ara C) in myelodysplastic syndromes
Authors: Tricot G. , Bock R. De , Dekker A. W. , Boogaerts M. A. , Peetermans M. , Punt K. , Verwilghen R. L. 
Published: March 2008

SummaryMyelodysplastic syndromes (MDS) are acquired bone‐marrow disorders, characterized by a decreased ability of the haemopoietic cell to differentiate, resulting in peripheral cytopenias. The majority of patients will die either from acute myeloid leukaemia or from infection and/or haemorrhage. Thirty‐eight courses of low dose Ara C were administered in 26 MDS patients. Nineteen courses (50%) were associated with good (12) or partial (7) response. Three complete remissions were observed. The median duration of response overall was 19‐5 weeks, 26 weeks for the good and 10 weeks for the partial responders. A high incidence of treatment failure was seen in patients treated after transition to AML. Major complications were observed during 14 courses and mortality was directly related to therapy in five patients. Platelet transfusions were required during 26 courses. Aggravation of peripheral‐blood cytopenia during the first weeks and hypocellularity of bone‐marrow aspirates at the end of therapy suggest that low‐dose Ara C exerts its main activity by suppression of leukaemic growth, rather than by induction of differentiation in malignant cells. Our results in MDS patients demonstrate that low‐dose Ara C can be of value in severe cytopenia and can decrease the proportion of leukaemic cells in the bone marrow, but the danger of treatment should not be underestimated.
Separation of human bone marrow by counterflow centrifugation monitored by DNA‐flowcytometry
Authors: Witte T. DE , Plas A. , Koekman E. , Blankenborg G. , Salden M. , Wessels J. , Haanen C. 
Published: March 2008

SUMMARYHuman bone marrow was fractionated by counterflow centrifugation into 16 fractions with increasing cell size. Three distinct subpopulations could be recognized: small lymphocytic cells, medium‐sized nucleated erythroid cells and large myeloid elements. DNA‐flowcytometry and 3H‐thymidine uptake showed that within the erythroid and myeloid cell populations counterflow centrifugation separates each population according to the cell cycle phase. Hypotonic treatment of bone marrow for removal of the erythroid nucleated cells resulted in a complete abrogation of the proliferating erythroid cell population. Counterflow centrifugation also separates the small non‐proliferating myeloid and erythroid committed stem cells from the larger proliferating stem cells. It appeared feasible to separate the small lymphocytic cells from the majority of BFU‐E and CFU‐GM, due to the larger size of the proliferating normoblasts and the committed progenitor cells. Elimination of the mature lymphocytes from the haematopoietic stem cells by counterflow centrifugation may offer an alternative approach to the prevention of graft versus host disease (GvHD).
Inverse correlation between age related abnormalities of T‐cell immunity and circulating thymosin α1 levels in haemophilia A
Authors: Kessler Craig M. , Schulof Richard S. , Alabaster Oliver , Goldstein Allan L. , Naylor Paul H. , Phillips T. M. , Luban Naomi L. C. , Kelleher Jack F. , Reaman Gregory H. 
Published: March 2008

SummaryT‐cell immunity and serum levels of thymosin α1, β2‐microglobulin, circulating immune complexes, serum immunoglobulin levels, antibodies to hepatitis surface or core antigen, and to cytomegalovirus, and Epstein‐Barr virus were investigated in 51 patients with haemophilia A ranging in age from 2 to 52 years. All patients had received commercial U.S. lyophilized concentrates of antihaemophilic factor (AHF). The mean helper/cytotoxic‐suppressor (0KT4/0KT8) ratio of 11 pre‐adolescents (1‐6 ±0‐4 SE) was not significantly different from that of age matched normal controls. In contrast, the mean 0KT4/0KT8 ratios of 13 adolescent (1‐2 ±0‐2 SE) and 23 adult (0‐8 ±0‐1 SE) haemophiliacs were significantly reduced. Abnormalities of lymphocyte mitogenic responses were found only in adult haemophiliacs. Nine individuals treated with commercial U.S. prothrombin complex concentrates for antibodies directed against AHF or for haemophilia B had normal mean OKT4/OKT8 values. The mean serum thymosin α1 levels for each age category was similar to that of age matched controls; however, regression analysis revealed a significant relationship between elevated thymosin α1 levels and decreased OKT4/OKT8 ratios in adult haemophiliacs (P= 0‐012). Although the mean serum level of β2‐microglobulin was significantly increased in the adult haemophiliac group, there was no correlation between OKT4/OKT8 ratios and any of the other serologic parameters studied.
Expression of SSEA‐I antigen (3‐fucosyl‐N‐acetyl‐lactosamine) on normal and leukaemic human haemopoietic cells: modulation by neuraminidase treatment
Authors: Tabilio A. , Canizo M. C. Del , Henri A. , Guichard J. , Mannoni P. , Civin. C.I. , Testa U. , Rochant H. , Vainchenker W. , Breton‐Gorius J. 
Published: March 2008

SummarySeveral mouse monoclonal antibodies (MoAbs) considered specific for the myeloid lineage recognize the same carbohydrate structure (3‐fucosyl‐N‐acetyl‐lac‐tosamine) which is similar to the murine antigen SSEA‐I. We have investigated the expression of this antigen with six different well‐characterized murine IgM MoAbs on normal, leukaemic, and cultured cells by immunofluorescence and immuno‐electron microscope cytochemistry. The cells were studied before and after neuraminidase treatment since epitopes recognized by these MoAbs may be masked by sialic acid. Among the recognizable normal marrow or blood cells, all these MoAbs specifically labelled the granulocytic lineage from the promyelocyte to the polymorph. After neuraminidase treatment, monocytes became labelled. All the other lineages remained unstained. Several cell lines were studied. Six of eight lymphoblastoid cell lines were stained by these MoABs; reactivity was increased by neuraminidase. One Burkitt cell line and two T cell lines were also found to be positive. These antibodies were tested on leukaemic cells. In acute non‐lymphocytic leukaemia they usually labelled promyelocytes, more mature granulocytic and monocytic precursors but did not label myeloblasts; after neuraminidase treatment, these myeloblasts became stained. No labelling was observed on leukaemic proerythroblasts and promegakaryoblast before and after neuraminidase treatment except in one case of promegakaryoblastic leukaemia in which the SSEA‐I antigen and platelet peroxidase were expressed in the same cell. In addition, six cases of common acute lymphoblastic leukaemia were studied; the blasts became positive after desialylation. Two examples of T cell acute leukaemia were essentially negative. We conclude, therefore, that the reactivity of haemopoietic cells with these MoAbs alone does not represent a criterion sufficient to sustain their myeloid origin since the SSEA‐I antigen may be expressed at the surface of all cell lineages in the early phases of haemopoietic differentiation.
Multimarker phenotypic characterization of adult and childhood acute lymphoblastic leukaemia: an Italian multicentre study
Authors: Foá R. , Baldini L. , Cattoretti G. , Foa P. , Gobbi M. , Lauria F. , Madon E. , Masera G. , Miniero R. , Paolucci P. , Perona G. , Pizzolo G. , Saitta M. , Gavosto F. 
Published: March 2008

Summary. A multicentre phenotypic study was carried out in Italy combining conventional immunological techniques with monoclonal antibody (MoAb) analysis in 190 cases of adult and childhood acute lymphoblastic leukaemia (ALL), in an attempt to define better the lineage relationship of the neoplastic cells. Of the 140 children evaluated, 79·3% expressed the common ALL (cALL) antigen (all analyses performed by MoAb), 11·4% were T‐ALL and 9·3% were non‐T, non‐B, non‐common (‘null’) ALL. The proportion of adult cALL cases was slightly lower (64% of the 50 cases studied) than that of childhood ALL, whilst the incidence of T‐ALL was significantly higher in adults than in children (26%v. 11·4%, P <0·05). Because of the high proportion of cALL cases, the incidence of ‘null’ ALL in adult patients was similar (10%) to that of children, and lower than previously reported. The recognition of early pre‐T‐ALL cases (T1+, RFT2+, T10+, T6‐, T11‐, E‐) contributed to the overall low proportion of ‘null’ ALL; prior to the use of MoAb, such cases would probably have been classified as undifferentiated acute leukaemia or ‘null’ ALL. The search for B‐cell‐related markers showed that the incidence of pre‐B‐ALL cases (cytoplasmic immunoglobulin positive cases) was similar in adults and in children (25·6% and 32%, respectively). Furthermore, the great majority of cases studied expressed the BA‐1 antigen (92·8% of adults and 79% of children), whilst the BA‐2 antigen was found in 53% of cases (tested only in children), confirming a hierarchy in the expression of B‐cell related markers in CALL: BA‐1, BA‐2, Cylg. Several of the ‘null’ cases also expressed the BA‐1 antigen on a variable proportion of cells, pointing to a possible B‐cell origin of the blasts.This multicentre study shows that both in adult and in childhood ALL thecombined use of conventional immunological markers and of a panel of MoAb allows identification of the cell lineage of the great majority of cases, thus reducing the number of ‘null’ ALL. Furthermore, these findings suggest that practically all cases of ALL belong either to the T or to the B cell compartment and that the neoplastic cells appear blocked at different levels along the lymphoid differentiation pathway.
Blood coagulation and fibrinolysis in heat stroke
Authors: Mustafa Khatim Y. , Omer O. , Khogali M. , Jamjoom A. , Gumaa K. A. , El‐Nasr N. Abu , Gader M. A. 
Published: March 2008

Summary. Blood coagulation and fibrinolysis were assessed in 55 cases of heat stroke who presented with or without bleeding tendencies during the Makkah pilgrimage of 1983. 17 patients were identified to have evidence of disseminated intravascular coagulation (DIC). Bleeders with DIC had a higher incidence of shock and a higher mortality when compared to non‐bleeders. Thrombocyto‐penia and liver cell damage were not limited to cases with DIC. Coagulation factors and serum enzyme studies suggested non‐specific tissue damage as the trigger mechanism for DIC possibly proceeding through the extrinsic system of blood clotting.We conclude that the breakdown of haemostasis in heat stroke is multifactorial: thrombocytopenia, liver cell damage and DIC.
Acute biphenotypic leukaemia (myeloid and null‐ALL type) supervening in a myelodysplastic syndrome
Authors: Eridani S. , Chan L. C. , Halil O. , Pearson T. C. 
Published: March 2008

Summary. An acute leukaemia was seen in a 72–year‐old patient with a myelodysplastic syndrome (MDS) of 14 months duration, who had been treated only with steroids. The morphological appearance of the blast cells suggested a poorly differentiated cell type. Surface marker analysis, including double staining studies, showed the coexistence of a population of null acute lymphoblastic leukaemia (ALL) blast cells together with acute myeloid leukaemia type cells. No chromosomal alterations were detected.The change from a chronic MDS to an acute leukaemia of mixed (myeloid and null ALL) type suggests either transformation of a pre‐existing abnormal clone or de novo appearance of two separate leukaemic clones.
Post‐transfusion purpura responding to high dose intravenous IgG: further observations on pathogenesis
Authors: Berney S. I. , Metcalfe P. , Wathen N. C. , Waters A. H. 
Published: March 2008

Summary. A typical case of post‐transfusion purpura (PTP) is described in a 61‐year‐old woman. Treatment with steroids corrected the purpuric manifestations, but the patient remained thrombocytopenic in spite of steroid therapy and plasma exchange. However, an intravenous infusion of high dose IgG led to a rapid and sustained increase in the platelet count.The mechanism of thrombocytopenia in PTP is still a matter for speculation, as the platelet specific antibody usually cannot be shown to react with the patient's own platelets in vitro. Therefore, the finding of a coexistent platelet specific IgM autoantibody in this patient, first detected during the early recovery phase, is of particular interest and suggests a possible autoimmune basis for the profound thrombocytopenia.
Electrophoretic analysis of red blood cells in polycythaemia
Authors: Brown K. A. , Guthrie D. L. , Pearson T. C. , Roche C. , Crawford N. 
Published: March 2008

Summary. In contrast with previously published observations, this study has found no increase in the net negative surface charge of the red blood cells (RBC) from patients with various forms of polycythaemia when compared with normal subjects.Two sub‐populations of RBCs with different electrophoretic mobilities (EPM), termed fast and slow, were present in samples from both patients and normal individuals. Frequently, the slow cell population in RBCs from patients with polycythaemia, particularly the apparent polycythaemia sub‐group, was of a lower EPM and contained more cells than the corresponding population in normal subjects.The membrane‐bound sialic acid content of RBCs from patients with primary proliferative polycythaemia, associated with iron deficient RBC changes, was increased if the results were expressed per unit volume of RBCs and decreased if the sialic acid concentration was presented per number of RBCs.These results imply that differences in surface charge of RBCs are of no value in discriminating between primary and secondary polycythaemia.