bluuebunny/crossref_metadata_2025_split huggingface dataset:
The action of Russell's viper venom on fibrin formation and fibrinolysis in vivo
Authors: Woodhams B. J. , Than Thein , Than Than , Hutton R. A. 
Published: March 2008

SummaryEnvenoming by Russell's viper caused a marked rise in FPA, B beta 15‐42 fragment and fibrin derived cross‐linked D‐dimer fragment indicative of a consumptive coagulopathy with hyperfibrinolysis. There was no increase in tPA or tPA‐I levels post envenoming, which suggests that the increase in fibrinolytic activity was not due to venom‐induced release of tPA from the vessel walls but may have been attributable to a direct effect of the venom or to a secondary physiological response to fibrin deposition. The effectiveness of the antivenom is demonstrated by its ability to prevent further cleavage of fibrinogen and the return to normal of fibrinogen levels by 24 h. A secondary rise in FPA at this time indicates that the initial dose of antivenom may have been too small. The antivenom alone or in combination with the venom causes the release of tPA, tPA‐I and vWF by the vessel walls. This may be a consequence of the severe anaphylactic reactions seen in some patients.
Recombinant human erythropoietin has little influence on megakaryocytopoiesis in mice
Authors: Grossi Alberto , Vannucchi Alessandro M. , Rafanelli Daniela , Ferrini Pierluigi Rossi 
Published: March 2008

Summary. The availability of a preparation of recombinant human erythropoietin (rEp) prompted us to investigate the role of Ep in the regulation of megakaryocytopoiesis in mice, using experimental procedures by which the effects on the mitotic and post‐mitotic compartment of megakaryocytes could be evaluated separately. In agar cultures of murine bone marrow cells, either serum‐depleted or serum‐supplemented, rEp (0.1–2 U/ml) did not stimulate megakaryocyte colony formation and when it was added to suboptimal amount of spleen cell‐conditioned medium (SCM), it failed to show a significant synergistic activity. On the contrary, rEp increased the number of megakaryocytic colonies developed from splenic precursors in the presence of suboptimal amounts of SCM, although it was unable per se to stimulate colony formation.The effects of rEps on megakaryocyte maturation and platelet production were studied in vivo evaluating the incorporation of 75Se‐selenomethionine into platelets, the platelet count and platelet size, and the number of megakaryocyte precursors (small acethylcholinesterase positive cells, sAchE) in the bone marrow of mice injected with 1–8 U of rEp. No modification of these parameters was found in comparison with control mice. On the other hand, rEp increased the number of recognizable splenic megakaryocytes in a dose‐dependent fashion.These data suggest that rEp has little influence on megakaryocytopoiesis, at least at the doses we used and which are known to elicit a maximal response of erythropoiesis. However, a subset of megakaryocytes with particular kinetic properties, such as those in the spleen of mice, may be responsive to relatively high doses of rEp. The significance of this observation in the overall regulation of megakaryocytopoiesis remains to be determined.
HRAS1 and INS genes are relocated but not structurally altered as a result of the t(7;11) (p15;p15) in a clone from a patient with acute myeloid leukaemia (M4)
Authors: Morris C. M. , Fitzgerald P. H. , Kennedy M. A. , Hollings P. E. , Garry M. , Corbett G. M. 
Published: March 2008

Summary. A patient whose leukaemic cells carried the rare t(7;11)(p15;p15) was diagnosed as having acute myelomonocytic leukaemia (AML‐M4), and supports the association of this specific translocation with forms of acute myeloid leukaemia showing differentiation. Blast phase chronic myeloid leukaemia was excluded by lack of involvement of the ABL and BCR genes.Chromosome in situ hybridization studies showed that both the HRAS1 and INS genes were present on the terminal part of chromosome 11p which was translocated to chromosome 7p. Neither HRAS1 nor INS were structurally rearranged. Field inversion gel electrophoresis showed that a 400 kb fragment encompassing HRAS1 was structurally entire in leukaemic DNA. Because the INS gene, which was also translocated, is probably located proximal to HRAS1 on chromosome 11p. it is unlikely that HRAS1 was near the chromosome 11 breakpoint or involved in this leukaemia.
On the diagnosis of erythrocyte enzyme defects in the presence of high reticulocyte counts
Authors: Lakomek M. , Schröter W. , De Maeyer G. , Winkler H. 
Published: March 2008

Summary. The separation of red blood cells into reticulocytes and young and old erythrocytes enables investigations of fractions with different contents of reticulocytes. Activities of hexokinase, glucose phosphate isomerase, phosphofructokinase, pyruvate kinase and glucose‐6‐phosphate dehydrogenase showed a linear relationship to reticulocyte counts. The dependence of these enzyme activities on the age of the red blood cells exhibited a strong decline from the reticulocyte to the young erythrocyte stage followed by only little further loss of activity, thus leading to a biphasic decay of enzyme activities.By linear regression analysis enzyme activities in erythrocytes (AE) and reticulocytes (AR) could be evaluated. The activity of a given enzyme in the reticulocyte exceeded that of the erythrocyte; the quotient AR/AE represents the decline of enzyme activity from the reticulocyte to the erythrocyte stage. This value AR/AE is 16·7 for pyruvate kinase and 9·4 for hexokinase and thus considerably higher than that for the other enzymes investigated (glucose phosphate isomerase: 2·9, phosphofructokinase: 4·3, glucose‐6‐phosphate dehydrogenase: 4·5). In patients suffering from erythrocyte enzymopathies, the AR/AE for pyruvate kinase was 16·2 and thus almost identical to the normal enzyme.Calibration curves where the enzyme activity is plotted versus the fraction of reticulocytes enable the determination of normal activity of a given erythrocyte enzyme depending on the content of reticulocytes in red blood cell suspensions. Thus an unambiguous diagnosis of enzyme defects irrespective of reticulocyte counts becomes possible.
Detection of monoclonal B lymphocytes in bone marrow and peripheral blood of multiple myeloma patients by immunoglobulin gene rearrangement studies
Authors: Van Riet Ivan , Heirman Carlo , Lacor Patrick , Waele Marc De , Thielemans Kris , Van Camp Ben 
Published: March 2008

SummaryTo investigate whether B lymphocytes are involved in the malignant cell clone of multiple myeloma (MM), we performed immunoglobulin gene rearrangement analysis of mononuclear cells and separated B lymphocytes, isolated from bone marrow and peripheral blood of MM patients. The B lymphocytes were separated by immunomagnetic beads, coated with an HLA class II specific antibody. Southern blot analysis with a JH probe revealed in the bone marrow of three out of seven patients identical immunoglobulin gene rearrangements in the B lymphocytes when compared to the plasma cells. Out of 10 patients, two patients with a high tumour burden were found to have monoclonal B lymphocytes in the peripheral blood. These results suggest that B lymphocytes in the bone marrow are part of the myeloma clone and that they can circulate in the peripheral blood. Although previous studies indicated that the ratio of K to λ bearing lymphocytes in the peripheral blood can provide evidence for B cell monoclonality, we did not find a correlation between the results of K/λ analysis and immunoglobulin gene rearrangement.
Analysis of surface antigen expression of human immunoglobulin‐secreting cells: phenotypic heterogeneity in normal counterparts of myeloma cells
Authors: Tominaga Nobuhiko , Katagiri Shuichi , Ohnishi Mitsunobu , Nakao Hirohisa , Oritani Kenji , Yagura Hirosuke , Tamaki Toshiharu , Kanayama Yoshio , Yonezawa Takeshi , Tarui Seiichiro 
Published: March 2008

SummaryHuman myeloma cells are malignant counterparts of plasma cells which represent the most differentiated B cells. Myeloma cells are, however, heterogeneous in their surface antigen expression (Katagiri et al, 1984, 1985), which may reflect that normal plasma cells have a spectrum of differentiation. To test this hypothesis, immunoglobulinsecreting cells (ISC) of non‐neoplastic nature were studied with regard to their surface antigen expression by using a combination of reverse haemolytic plaque assay and complement‐dependent cytolysis. Non‐neoplastic ISC were found to have a broad spectrum of differentiation stages from the immature type of CD20+, HLA‐DR+, CD38+ in the peripheral blood to the mature type of CD20–, HLA‐DR–, CD38+ in the bone marrow. In patients with polyclonal B cell activation (PBA), ISC showed a more immature antigen expression in comparison with ISC in normal controls or patients without PBA. The surface antigen development of ISC was clearly demonstrated throughout the stages in the analysis of mitogen‐induced ISC in vitro. No significant difference in the surface phenotype of ISC was found among heavy chain classes. Thus, non‐neoplastic ISC show a spectrum of differentiation similar to that of myeloma cells, depending on the site where ISC are located, and on the degree of PBA in vivo.
Biological and clinical features of acute lymphoblastic leukaemia with cytoplasmic granules or inclusions: description of eight cases
Authors: Cantù‐Rajnoldi Angelo , Invernizzi Rosangela , Biondi Andrea , Banfi Patrizio , Zoia Adele , Fazio Pasqualina De , Polli Nicoletta 
Published: March 2008

SummaryWe describe eight patients (four children and four adults) with an acute lymphoblastic leukaemia (ALL) with cytoplasmic granules or inclusions. The incidence of this variant of acute leukaemia in our whole series of patients with ALL is 1.8%. The granules or inclusions were usually positive for aspecific esterases (ANAE) and/or acid phosphatase, and the immunophenotype was in all cases typical of a CALLA positive B‐lineage ALL (CD10+, CD19+ and/or CD24+, DR+, TdT+, anti‐T‐, anti‐My‐, SIg‐). In one paediatric case, CD33 was unusually coexpressed. Ultrastructural investigations were performed in one case and demonstrated large granules containing vesicles, usually membrane bound, in the majority of blast cells. In the two cases analysed, Ig heavy chain gene rearrangement was detected. In this series of patients prognosis was poor since three never achieved a complete remission, four relapsed and only one is still in first continuous remission.
Long‐term results of the CHOP regimen in stage C chronic lymphocytic leukaemia
Authors:   French Cooperative Groupon Chronic Lymphocytic Leukaemia
Published: March 2008

SummaryThis paper reports the results of the third interim analysis of a randomized clinical trial in poor prognosis chronic lymphocytic leukaemia (stage C). From May 1980 to February 1985, 70 stage C patients were randomized between the two polychemotherapies COP and CHOP (COP+doxorubicin). At the reference date of 1 June 1987 used for this analysis, the mean follow‐up was 58 months, 46 deaths were observed, 27 in the COP group and 19 in the CHOP group. Overall survival was significantly improved in the CHOP group (P= 0.0005). The 3‐year survival rates were 71% in the CHOP group and 28% in the COP group and the median survival times were 62 months in the CHOP group as compared to 22 months in the COP group. This benefit with CHOP was confirmed when adjusting treatment comparison for nine parameters (P= 0.001) and when considering other endpoints than survival, namely 9‐month status and stage. This third interim analysis confirms the results of the first interim analysis that led to an early stopping of this clinical trial and clearly indicates the beneficial effect of low doses of doxorubicin in advanced chronic lymphocytic leukaemia.
Cytokine activity after human bone marrow transplantation III. DEFECT IN IL2 PRODUCTION BY PERIPHERAL BLOOD MONONUCLEAR CELLS IS NOT CORRECTED BY STIMULATION WITH Ca++ IONOPHORE PLUS PHORBOL ESTER
Authors: Cooley Margaret A. , McLachlan Karen , Atkinson Kerry 
Published: March 2008

SummaryPrevious studies have shown that interleukin 2 (IL2) production by peripheral blood mononuclear cells (PBMC) is severely impaired post allogeneic bone marrow transplantation, whereas production of interferon‐γ (IFN‐γ) is at most marginally depressed. To investigate the mechanisms behind this apparently differential inhibition of lymphokine production, we stimulated PBMC from recipients of HLA‐identical sibling bone marrow transplants with phytohaemagglutinin (PHA), PHA + phorbol ester (PMA) (to bypass accessory cell requirements) or Ca++ ionophore + PMA (to bypass both accessory cell and T cell surface receptor (CD2 and/or CD3/Ti interactions). Increasing the potency of the stimulus increased the amount of IL2 and IFN produced by PBMC from both normal volunteers and from marrow transplant recipients, but for each stimulus the amount of IL2 produced by marrow transplant recipient PBMC remained 10–100‐fold lower than that produced by normal PBMC, suggesting an underlying defect in IL2 production by marrow transplant recipient T cells, not due to accessory cell or CD2 defects. Selection experiments showed that CD3+ cells were the primary IL2 producers, and we were unable to demonstrate presence of suppressor cells in marrow transplant PBMC. Statistical analysis of the clinical factors possibly affecting lymphokine synthesis showed that in vivo cyclosporin A did not affect the in vitro capacity of PBMC to produce cytokines, although steroid therapy had a negative effect on IL2 production. The only variable significantly affecting IL2 and IFN production in marrow transplant recipients was increasing time post transplant. It is suggested that the defect in IL2 but not IFN production could be due to either a selective reduction in the frequency of IL2 producing cells as opposed to IFN producing cells, or to a reduction in the amount of IL2 produced per cell in marrow transplant recipients.
Autoantibodies to platelet glycoproteins in patients with disease‐related immune thrombocytopenia
Authors: Berchtold Peter , Harris Jeffrey P. , Tani Patricia , Piro Lawrence , McMillan Robert 
Published: March 2008

SummaryAlthough increased platelet destruction and elevated platelet‐associated IgG have been shown in patients with lymphomas and various autoimmune diseases, such as systemic lupus erythematosus (SLE), there have been few studies evaluating autoantibodies against platelet‐specific antigens. We evaluated 24 patients retrospectively with disease‐related thrombocytopenia (12 with lymphoproliferative diseases and 12 with various autoimmune disorders) using a recently reported antigen‐specific assay.Autoantibodies against platelet GPIIb/IIIa or GPIb/IX were noted in 15 of the 24 patients (10 of 12 with autoimmune disease and five of 12 with lymphoproliferative disorders). Platelet‐associated autoantibodies were present in 60% and plasma autoantibodies in 33%. Anti‐GPIIb/IIIa autoantibodies were much more common than those against GPIb/IX.In one patient each with thrombocytopenia and either SLE or myasthenia gravis, absorption of plasma with platelets completely removed the anti‐GPIIb/IIIa autoantibodies, but did not affect the level of anti‐cochlear autoantibody involved with immune‐mediated hearing loss in the SLE patient or the anti‐acetylcholine receptor autoantibody in the myasthenic patient.These findings show that, in some cases of disease‐related immune thrombocytopenia, autoantibodies against GPIIb/IIIa or GPIb/IX can be detected similar to those seen in chronic ITP. As shown in two patients with multiple autoimmune manifestations, the various autoantibodies have diverse specificities and do not crossreact.
A spectrophotometric method for the assay of pyrimidine 5′‐nucleotidase in human erythrocytes
Authors: Amici Adolfo , Natalini Paolo , Ruggieri Silverio , Vita Alberto , Magni Giulio 
Published: March 2008

SummaryA new spectrophotometric assay for human erythrocyte pyrimidine 5′‐nucleotidase using a continuous spectrophotometric method is described. The activity is detected by measuring uracil, which is produced by a coupled assay including cytidine deaminase and uridine nucleosidase. The results obtained with the continuous spectrophoto‐metric method have been confirmed by high pressure liquid chromatography (HPLC) analysis. This procedure, not based upon inorganic phosphate formation and avoiding the use of radioactive material, offers significant advantages with respect to commonly adopted assays.
Interleukin 3 alone does not support the proliferation of bone marrow cells from A/J mice: a novel system for studying the synergistic activities of IL‐3
Authors: Morris C. F. , Salisbury J. , Kobayashi M. , Townsend P. V. , Hapel A. J. 
Published: March 2008

SummaryThe number of colonies produced by bone marrow cells in response to interleukin 3 (IL‐3) in soft agar cultures varies according to the strain of the donor mice. A/J, AKR, A.TH and A.TL bone marrow cells are particularly hyporesponsive, producing only occasional colonies in the presence of IL‐3. Bone marrow cells from all strains of mice, including A/J, produce distinctively large colonies in response to the combination of IL‐3 and macrophage colony stimulating factor (M‐CSF). In cultures of A/J bone marrow cells, the synergy between IL‐3 and M‐CSF is further reflected in an increase in both the number and the variety of colonies produced. The increase in colony numbers may be due to the priming of a population of A/J colony‐forming‐cells (CFCs) by IL‐3, enabling them to respond to M‐CSF. In support of this notion, IL‐3 enhances the level of c‐fms (M‐CSF receptor) messenger RNA in cultures of A/J bone marrow cells. It is also possible that a subpopulation of CFCs requires both IL‐3 and M‐CSF as co‐mitogens. The A/J strain provides a novel system for studying the mechanisms involved in the interaction between IL‐3 and M‐CSF in haemopoiesis.
Platelet activation by CD9 monoclonal antibodies is mediated by the FCγII receptor
Authors: Worthington Ronald E. , Carroll Roger C. , Boucheix Claude 
Published: March 2008

SummaryThe function of the human cell surface CD9 antigen is not known, yet monoclonal antibodies (mAbs) of the IgG1 subclass in the CD9 cluster induce activation of platelets. Previously it had been shown that this activation pathway is comparable both in kinetics and extent to physiological agonists such as thrombin. Here it is demonstrated that activation with CD9 mAbs depends on interaction of the Fc part of the CD9 antibody molecule with Fc receptors on the platelet surface, since: (i) mAb directed against the Fc receptor totally blocked the platelet response to CD9 mAb; and (ii) F(ab')2 fragments of the CD9 mAb SYB‐1 which bound to platelets, as demonstrated by flow cytometry, failed to activate them. Furthermore, platelet activation by CD9 mAb closely paralleled the activation caused by crosslinking Fc receptors when comparing: (i) kinetics and extent of aggregation; (ii) thromboxane synthesis; (iii) calcium flux: and (iv) the cytoplasmic alkalinization response. Thus it is concluded that CD9 antigen itself does not necessarily participate in stimulus‐response coupling leading to platelet activation by CD9 mAbs, and that this activation can be entirely accounted for by the Fc receptor pathway mechanism. The results suggest a possible novel mechanism for platelet consumption in cases of immune thrombocytopenia.
In vitro suppressor T lymphocyte dysfunction in autoimmune thrombocytopenic purpura associated with a complement‐fixing antibody
Authors: Hymes Kenneth B. , Karpatkin Simon 
Published: March 2008

SummaryIg secretion of peripheral blood mononuclear cells (PBMC) was measured in Epstein Barr virus (EBV) seropositive autoimmune thrombocytopenic purpura (ATP) patients and controls following in vitro infection with EBV. EBV infected PBMC from patients with ATP secreted Ig for a longer period of time than EBV infected control cells and had higher peak Ig production. Removal of T cells or CD8 cells from control PBMC increased the duration and level of Ig production to that achieved by ATP PBMC. Total T or CDS cell depletion of ATP PBMC had no effect on the enhanced level or duration of Ig secretion. Depletion of control CD4 lymphocytes decreased Ig production.Treatment of EBV infected control PBMC with either ATP sera or purified IgG (plus complement) increased the duration and level of production of Ig to that observed in ATP PBMC, control PBMC depleted of all T cells or control PBMC depleted of CD8 cells. This antibody effect could be reversed by reconstitution with control T cells. Thus, patients with ATP produce an antibody which leads to suppressor cell dysfunction. Defective function of these cells may lead to a disorder of immune regulation in which autoantibodies are produced against platelets.
Long‐term bone marrow damage after chemotherapy for acute myeloid leukaemia does not improve with time
Authors: Chang J. , Geary C. G. , Testa Nydia G. 
Published: March 2008

SummaryThirteen patients with acute myeloid leukaemia (AML) who had been in unmaintained complete remission for at least 5 years following successful chemotherapy, were studied by marrow culture techniques regularly for periods of up to 5 years. In 10 patients, short‐term clonal assay revealed the incidence of granulocyte‐macrophage progenitor cells (GM‐CFC) to be at the lower limit of the normal range; but three showed wide fluctuations in GM‐CFC numbers. Moreover the generation of GM‐CFC in long‐term bone marrow culture (LTBMC) was impaired in eight of nine evaluable patients. These results suggest that, despite normal blood counts, impairment of haemopoiesis persists in patients who are long‐term survivors of AML, and this does not improve with the passage of time.
HLA class I expression on erythrocytes and platelets from patients with systemic lupus erythematosus, rheumatoid arthritis and from normal subjects
Authors: Botto Marina , So Alex K.‐L. , Giles Carolyn M. , Mason Philip D. , Walport Mark J. 
Published: March 2008

SummaryIt has previously been shown, by a haemagglutination assay, that patients with systemic lupus erythematosus (SLE) express increased levels of HLA class I on erythrocytes compared with normal subjects and patients with rheumatoid arthritis (RA). A radioligand‐binding assay, using monoclonal antibody W6/32, was devised to quantify HLA class I expression on erythrocytes and platelets. An increased number of class I molecules was expressed on erythrocytes from 45 patients with SLE (mean = 354 molecules per cell, median = 255 molecules, range = 30–1270 molecules per cell), compared with cells from 46 normal subjects (mean = 132, median = 78, range = 40–550) and 31 RA patients (mean = 132, median = 89, range = 26–497). The presence of HLA‐B7 correlated with increased class I expression on erythrocytes from both normal subjects and patients with SLE. Levels of HLA class I in serum were measured. All subjects with HLA‐A9 (A23, 24) showed higher levels of serum class I than their A9‐negative counterparts, and there was no difference in levels between SLE patients and normal subjects. There were no correlations between class I levels in serum and on erythrocytes amongst SLE patients or normal subjects. Red cells were fractionated, according to their age in vivo, on Percoll gradients. Class I levels fell with increasing erythrocyte age in all individuals, but were higher in all fractions from SLE patients compared with age‐matched fractions from normal subjects. HLA‐B7‐positive erythrocytes also expressed higher class I levels in each Percoll fraction, compared with their HLA‐B7‐negative counterparts, suggesting that enhanced B7 expression is not due to greater structural stability of this class I allotype. These data are compatible with the hypothesis that class I is expressed as an intrinsic protein of erythrocyte membranes and that expression is increased amongst patients with SLE.