bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cell‐mediated cyclic thrombocytopenia treated with azathioprine
Authors: Dan Kazuo , Inokuchi Kohichi , An Emi , Nomura Takeo 
Published: March 2008

SummaryWe studied a male patient with cyclic thrombocytopenia whose bone marrow megakaryocyte count showed cyclic fluctuations in synchrony with cyclic changes of platelet count. He failed to respond to either prednisolone or bolus methylprednisolone therapy, but subsequently he was successfully treated with azathioprine. To investigate the underlying pathogenesis of the cyclic fluctuations in the platelet count. we studied the kinetics of megakaryocyte progenitor cells (CFU‐Meg) and the effects of the patient's peripheral blood mononuclear cells on CFU‐Meg. In one cycle of the platelet fluctuation, the increase in the CFU‐Meg number preceded an increase in the bone marrow megakaryocyte count and then the platelet count. In the latter half of the cycle, CFU‐Meg, bone marrow megakaryocytes and platelets began to decrease in that order. Peripheral blood mononuclear cells obtained from the patient in the thrombo‐cytopenic phase suppressed megakaryocyte colony formation from normal bone marrow cells in a dose‐dependent manner. In contrast, these cells obtained in the phase of a normal platelet count did not suppress megakaryocyte colony formation at all. These findings indicate that the cause of platelet fluctuation is periodic failure of megakaryocytopoiesis at the stage of CFU‐Meg and that the patient's peripheral mononuclear cells are responsible for periodically suppressing the CFU‐Meg.
Reduction of platelet glycoprotein Ib in uraemia
Authors: Sloand E. M. , Sloand J. A. , Prodouz K. , Klein H. G. , Yu M. W. , Arvath L. H. , Ricke W. F. 
Published: March 2008

SummaryPatients with uraemia have abnormal platelet function that may be partially corrected by haemodialysis, cryoprecipitate or 1‐desamino‐8‐d‐arginine vasopressin (DDAVP). We studied the platelet von Willebrand factor receptor. glycoprotein Ib (GPIb). and plasma von Willebrand factor (vWF) in uraemic patients undergoing chronic haemodialysis. Using the slope of agglutination of formalin‐fixed platelets as an index of response to ristocetin (with a constant amount of normal plasma as a source of vWF), we found the response of platelets from uraemic patients, both before (2·7± 1·5. n= 40) and after dialysis (1·2 ± 1·2, n= 40) to be significantly less than that for normal controls (14·1 ± 10·2. n= 20: P < 0·001). In addition, the agglutination response of platelets obtained after dialysis was less than that of platelets obtained before dialysis (P < 0·001). Immunoblotting demonstrated decreased or absent staining of glycocalicin, a subunit of GPIb, in platelet lysates from 25 patients. All platelet samples with reduced glycocalicin also had decreased responses to ristocetin. Tritium‐labelled platelets from seven patients showed decreased labelling of a protein with an electrophoretic mobility equivalent to that of GPIb (140000 daltons). In addition, platelets with the lowest levels of surface GPIb, as demonstrated by flow cytometry. also had decreased ristocetin agglutination and decreased staining on immunoblot. Levels of von Willebrand factor antigen and ristocetin cofactor in plasma from 10 patients were generally within the normal range, although post‐dialysis levels tended to be higher than pre‐dialysis levels. The pre‐ and post‐dialysis plasma vWF multimeric patterns were normal.
The haematology of homozygous sickle cell disease after the age of 40 years
Authors: Morris Joanne , Dunn David , Beckford Marjorie , Grandison Yvonne , Mason Karlene , Higgs Douglas , Ceulaer Karel De , Serjeant Beryl , Serjeant Graham 
Published: March 2008

SummaryHaematological indices have been studied in 181 patients with homozygous sickle cell (SS) disease aged 40–73 years. Cross‐sectional analyses in 5‐year age bands indicated age‐related decreases in HbF (males only), total haemoglobin and platelet counts. Longitudinal studies within individuals confirmed the downward age‐related trend in haemoglobin and platelets and also revealed a falling reticulocyte count, most significant when expressed as absolute values. Total nucleated cells also fell although the decline was significant only in females. These observations are consistent with a progressive bone marrow failure which is not explained by the commonly occurring renal impairment in older SS patients since the changes persisted in analyses confined to patients with normal creatinine levels. The mechanism of this bone marrow failure is currently unknown.
Fanconi's anaemia and pregnancy
Authors: Alter Blanche P. , Frissora Christine L. , Halpéirin Daniel S. , Freedman Melvin H. , Chitkara Usha , Alvarez Emanuel , Lynch Lauren , Adler‐Brecher Barbara , Auerbach Arleen D. 
Published: March 2008

SummaryWe have identified six new cases of Fanconi's anaemia (FA) who had pregnancies, and reviewed 11 others from the literature. At least 110 FA females have reached 16 years of age or more, of whom 15% became pregnant. There were a total of 26 pregnancies, resulting in 19 births and 18 surviving children. Anaemia and/or thrombocytopenia worsened during pregnancy in 10 patients, but five subsequently improved: seven had no haematological problems. Seven of the FA patients who had pregnancies died subsequently from cancer, and two from thrombocytopenic bleeding 3 and 20 years later. There were no peripartum deaths. Pregnancy in FA is clearly possible, with increased risks that are manageable from both the haematological and the obstetric aspects.
Is there a mechanical factor of haemolysis in patients with positive IgG‐type direct antiglobulin test?
Authors: Delamaire M. , Durand F. , Grosbois B. , Le Dantec G. , Dauriac C. , Le Goff M.‐C. , Le Blay R. , Genetet B. 
Published: March 2008

Summary. In autoimmune haemolytic anaemia, the presence of antibodies on the erythrocyte membrane results in haemolysis through an immune process, but does it not alter the rheological properties of red blood cells (RBC), thus adding a mechanical factor to haemolysis? This study was designed to examine the rheological properties of erythrocytes sensitized with IgG‐type antibodies. The study involved 20 patients with anaemia and positive direct antiglobulin test, including 12 with straightforward haemolysis, 10 samples sensitized in vitro, and 20 controls.The following haemorheological parameters were studied: erythrocyte filtration, blood and plasma viscosities, titration of adenosine triphosphate (ATP) and 2–3‐DPG, erythrocyte morphology under scanning electron microscopy.The results showed increased erythrocyte rigidity (P<0.025) as well as higher blood viscosity compared to controls with similar haematocrit values, and unaltered ATP and 2–3‐DPG (consistently with scanning electron microscope observations). These haemorheological disorders were more noticeable in patients with clear‐cut haemolysis, and there was a correlation between the increase in erythrocyte rigidity indices and the haemolytic parameters, especially haptoglobin (P<0.001). The in vitro study confirmed the results obtained ex vivo.To conclude, the mechanical properties of antibody‐coated erythrocytes are impaired, which may promote the immunological mechanism favouring haemolysis in the spleen.
Serum immunoreactive erythropoietin in patients with idiopathic aplastic and Fanconi's anaemias
Authors: Das R. E. Gaines , Milne Alison , Rowley Megan , Smith E. C. Gordon , Cotes P. Mary 
Published: March 2008

Summary. In patients with idiopathic aplastic anaemia (n = 34) and Fanconi's anaemia (n = 8), sampled once or on several occasions, serum erythropoietin (Epo) increased with increasing severity of anaemia with apparently similar rates of increase in each group. However, after adjustment for Hb, log Epo values for the Fanconi's anaemics tended to be greater than those for the idiopathic aplastic anaemics (P < 0·01).Erythropoietin concentrations in serum samples from patients with Fanconi's and idiopathic aplastic anaemias tended to be greater than in samples from patients with anaemias from protein energy malnutrition, myelodysplasia and iron deficiency.The results suggest that there is no deficiency of erythropoietin in Fanconi's and idiopathic aplastic anaemias and that if exogenous erythropoietin is of any benefit it would need to be administered in doses large enough to induce a significant increase in log Epo.Results of the study illustrate the need to take account of the assumptions which underlie interpretation of the statistical analysis. Use of erythropoietin values in place of log Epo gives misleading conclusions demonstrable as invalid as the conditions for normality of distribution of the data and homogeneity of variances were not satisfied.
Adjusted dose continuous infusion of factor VIII in patients with haemophilia A
Authors: Martinowitz U. , Schulman S. , Gitel S. , Horozowski H. , Heim M. , Taron D. 
Published: March 2008

Surgical interventions in patients suffering from haemophilia A require infusions of large doses of factor VIII (F VIII) concentrates. These are expensive and may pose a burden on the immune system, which is already compromised in many haemophiliacs. F VIII is usually given as bolus injections, although there are reports on fixed dose continuous infusion. We have developed a continuous infusion programme with dosage adjusted according to daily calculation of the clearance of F VIII.Twenty‐four haemophiliacs received a total of 205 d of continuous infusion with F VIII (168 d in hospital, 37 d home therapy). Eighteen patients underwent surgeries (11 elective, seven emergency) and six were treated for serious haemor rhages. We observed a significant, progressive decrease of the clearance of F VIII over the first 5 d from 3.2 (2.8–3.5) to 1.7 (1.3–1.9) ml/kg/h (median and interquartile range). The decrease of the clearance together with the fact that a continuous infusion requires less drug than bolus injections to keep the same minimal concentration, contributed to much lower doses of F VIII than reported in the literature or than required by historical controls, matched for the type of operation. Other advantages of our method are improved safety with stable activities of F VIII, lack of hazardous troughs below the haemostatic range, and the convenience, which permits ambulant therapy even when high doses of F VIII are required.
A sensitive sandwich ELISA for measuring erythropoietin in human serum
Authors: Noea Gudrun , Riedel Waltraut , Kubanek Bernhard , Rich Ivan N. 
Published: March 2008

Summary.A sandwich, non‐competitive enzyme‐linked immunosorbant assay (ELBA) for erythropoietin (EPO) is described. The ELISA utilizes a monospecific, polyclonal antibody raised in rabbits against human recombinant EPO (rhu EPO) and purified over a rhu EPO affinity chromatography column. The ELISA procedure can be summarized as follows: Anti‐EPO is coated onto 96‐well ELISA microtitre plates; standard EPO or sample is added and left to bind to this catching antibody: this is followed by the addition of the same antibody which has been biotinylated; finally, anti‐biotin conjugated to alkaline phosphatase is added and the enzyme reaction developed and read at 405 nm. All parameters of the assay have been optimized. Recombinant human EPO was standardized against the World Health Organization 2nd International Reference Preparation for erythropoietin. The minimal detectable concentration of rhu EPO was 0.3–0.5 mil/ml, which corresponded to 1.2–2 mU/ml of EPO in serum (serum diluted 1:4). No reaction was obtained with a variety of blood components and cytokines, indicating that the anti‐EPO antibody did not cross‐react with those substances to produce false‐positive results. The intra‐assay variation ranged from 3% to 10%, while the inter‐assay variation ranged from 8.5% to 24%. Serum dose‐response curves were parallel to the standard dose‐response curve. The assay is easy to use, rapid, reproducible, but above all quantitative, specific and sensitive to measure the EPO content in all serum samples.
Granulocytic differentiation of the human myelomonocytic leukaemia cell line ME‐1 in serum‐free culture
Authors: Yanagisawa Kohsuke , Hasegawa Hitoshi , Fujita Shigeru 
Published: March 2008

Summary.We have recently established ME‐1, a human myelomonocytic leukaemia cell line derived from acute myelomonocytic leukaemia with eosinophilia (M4E0). When ME‐1 cells were cultured in serum‐free medium, they stopped proliferating and began to differentiate morphologically, functionally and phenotypically to mature granulocyte‐like cells. The protein kinase inhibitor, 1‐(5‐isoquinolinyl‐sulphonyl)‐2‐methylpiperazine (H‐7) enhanced this differentiation dose‐dependently. Upon addition of fetal calf serum (FCS) to the serum‐free medium, the differentiation of ME‐1 cells into granulocyte‐like cells was inhibited and they resumed cell growth. We have recently reported that the differentiation of ME‐1 cells into macrophage‐like cells induced by IL‐3 and GM‐CSF involved the activation of protein kinase C. The present results indicate that ME‐1 is a bipotential cell line that can differentiate into granulocyte‐like cells or macrophage‐like cells, and that protein kinase C is closely related to each form of differentiation.
Diagnostic and clinical importance of interleukin‐2 receptor alpha chain expression on non‐T‐cell acute leukaemia cells
Authors: Nakase Kazunori , Kita Kenkichi , Otsuji Akira , Anazawa Hiroshi , Hoshino Kenichiro , Sekine Takao , Shirakawa Shigeru , Tanaka Isao , Nasu Kaori , Tsutani Hiroshi , Dohy Hiroo , Tsudo Mitsuru 
Published: March 2008

Summary.The expression of interleukin‐2 receptors (IL‐2R) was examined in 328 adult patients with non‐T‐cell (non‐T) acute leukaemia and blast crisis of chronic myelocytic leukaemia (CML.BC) using two monoclonal antibodies, anti‐Tac for IL‐2R α chain (IL‐2Rα) and Mikβ1 for IL‐2R β chain (IL‐2Rβ). Leukaemic cells in the following cases were positive for anti‐Tac; 28/192 of acute myelocytic leukaemia (AML), 24/44 CML‐BC, 4/28 CD19(+)CD10(‐) acute lympho‐blastic leukaemia (ALL), and 20/64 common ALL (c‐ALL). IL‐2Rβ was not detected on leukaemic cells of any case examined. Eleven of IL‐2Rα(+) AML were derived from myelodysplastic syndrome. None of the IL‐2Rα positive leukaemic cells responded to exogenous recombinant human IL‐2 (rhIL‐2) in culture. In addition, IL‐2Rα expression on non‐T leukaemic cells was closely correlated with coexpressing different lineage markers and the presence of the Philadelphia abnormality. Marked increase of serum soluble IL‐2Rα was demonstrated in the IL‐2Rα(+) patients examined. Clinically, the IL‐2Rα(+) patients showed significantly lower response to chemotherapy and poorer prognosis than IL‐2Rα(‐) patients. Our results clearly indicate the diagnostic importance of IL‐2Rα expression in non‐T acute leukaemia with a close relation to the particular cellular characteristics and the prognosis.
Possible evidence for genomic imprinting in childhood acute myeloblastic leukaemia associated with monosomy for chromosome 7
Authors: Katz Fay , Webb David , Gibbons Barbara , Reeves Brian , McMahon Cathy , Chessells Judith , Mitchell Christopher 
Published: March 2008

Summary.Monosomy or deletion of chromosome 7 is a frequent finding in both de novo and secondary acute myeloid leukaemia (AML) and myelodysplastic syndromes (MDS). Based on analysis of deletions of chromosome 7 in such patients, it has been suggested that there is a critical region of the chromosome lying within bands q21‐q31. We have examined bone marrow and peripheral blood samples from 10 patients with MDS, AML and biphenotypic acute leukaemia who had monosomy for or rearrangement of chromosome 7, seeking evidence of non‐random allele loss that might suggest the presence of imprinted genes on the chromosome.Bone marrow cells from one patient with the infant monosomy 7 syndrome had loss of maternal alleles as did two patients with biphenotypic leukaemia. Five out of five patients with MDS and both patients with de novo AML had loss of paternal alleles. One of the latter patients had a del(7) (q31q36) rather than monosomy 7. These findings suggest that imprinting of a gene(s) on chromosome 7, within the bands q31‐q36, may be of importance in MDS and AML.Despite the reported increased incidence of AML amongst relatives of patients with cystic fibrosis (CF) the gene for which lies in chromosome region 7q31, none of the patients nor parents studied here appeared to be carriers of the most common gene mutation seen in patients with CF, the delta F508.
Transfer of specific immunity from donor to recipient of an allogeneic bone marrow graft: effect of conditioning on the specific immune response of the graft recipient
Authors: Labadie J. , van Tol M.J. D. , Dijkstra N.H. , Zwaan F. E. , Vossen J. M. 
Published: March 2008

Summary.Transfer of specific immunity was investigated in a group of 28 paediatric and adult leukaemia patients during the first 100 d after allogeneic bone marrow transplantation (BMT). These patients and/or their donors were immunized 7–13 d before transplantation with the recall antigen tetanus toxoid (TT) and the neo‐antigen Helix pomatia haemocyanin (HPH). The recipients were booster immunized with both antigens at day 42 after transplantation. Transfer of a primary IgM and IgG response to HPH was successful in most paediatric and adult patients, but transfer of a secondary response to TT was established in only a few paediatric recipients. After booster immunization at day 42 most paediatric recipients responded with a rise in serum antibody titre to HPH as opposed to only two of 18 adult recipients. This incapability of the adult recipients to mount a secondary immune response may be related to their conditioning regimen which included Campath‐IG in vivo. The results from this study indicate that transfer of immunity against recall‐and neo‐antigens is possible. However, the establishment of long‐term memory may be affected by the regimen used to condition the graft recipient.
Studies on macromolecular activators of phagocytosis from platelets (MAPPs) using anti MAPP murine monoclonal antibodies
Authors: Yokoya Yukihiro , Sakamoto Haruhiko , Oryu Makoto , Uda Hirotsugu 
Published: March 2008

Summary.1‐MAPP(290 kD) and s‐MAPP(150 kD) are glycoproteins which have been shown to be involved in released products from platelets (PRPr) and to activate monocyte and neutrophil phagocytosis via the Fc receptors. Three IgG 2 a (κ) murine monoclonal antibodies against 1‐MAPP and nine IgG1 (κ) antibodies against s‐MAPP have been raised.By affinity chromatography using these monoclonal antibodies, active MAPPs were obtained from the supernatant of outdated platelet concentrates in the presence of 60% saturated ammonium sulphate and from PRPr‐rich medium, and substantial amounts of non‐functioning immunoreactive MAPPs were obtained from the precipitate.Fab fragments of one of the two anti 1‐MAPP and of two of the four anti s‐MAPP monoclonal antibodies inhibited the function of their corresponding MAPPs, but none of them could inhibit the other MAPPs.1‐MAPP and s‐MAPP in the platelets were visualized by indirect fluorescent antibody technique using Fab fragments of the antibodies.
Heparin‐associated thrombocytopenia in a patient treated with polysulphated chondroitin sulphate: evidence for immunological crossreactivity between heparin and polysulphated glycosaminoglycan
Authors: Greinacher A. , Michels I. , Schäfer M. , Kiefel V. , Mueller‐Eckhardt C. 
Published: March 2008

Summary.Heparin‐associated thrombocytopenia (HAT) type II, a severe side effect of heparin therapy, is thought to be induced by an immunological mechanism. By crossreactivity studies we have demonstrated that sera of patients with HAT type II activate platelets in vitro not only after the addition of heparin but also after addition of a chemically polysulphated chondroitin‐like substance, Arteparon®, used for treatment of degenerative joint disease. In addition here, we describe a patient who developed deep venous thrombosis and pulmonary embolism following administration of Arteparon® and typical HAT type II with thrombocytopenia, 36 h after the first administration of heparin. This patient had never received heparin, but had repeatedly been treated with Arteparon® for degenerative joint disease. We conclude that this patient had been presensitized by Arteparon®, as indicated by his clinical course. In vitro studies again confirm crossreactivity between heparin and Arteparon®.
Ratios of anti‐factor Xa to antithrombin activities of heparins as determined in recalcified human plasma
Authors: Schoen Pieter , Lindhoux Theo , Hemker H. Coenraad 
Published: March 2008

Summary.Anti‐factor Xa and anti‐thrombin activities of unfractionated (UF) and low molecular weight (LMW) heparins have been measured in human plasma and with purified human antithrombin III (ATIII) in the absence and presence of 1.5 mM calcium. The anti‐factor Xa and antithrombin activities were measured directly, by assessing the heparin‐dependent pseudo‐first order rate constants of inactivation of human factor Xa or thrombin. These activities were studied with the 4th International Standard for UF heparin, the 1st International Standard for LMW heparin, CY216, enoxaparin, CY222, and the synthetic pentasaccharide. In plasma, calcium equally well increased the specific anti‐factor Xa catalytic activities as compared to purified ATIII. That is. 1.5 mM calcium stimulated the UF standard heparincatalysed inactivation of factor Xa 2.1–2.4 times. In the presence of the LMW heparins the effect of calcium was smaller (1.3–1.7 times), and in plasma there was no effect of calcium on the pentasaccharide‐catalysed inactivation of factor Xa. Thus, the largest effects of calcium in the inactivation reaction of factor Xa is seen with UF standard heparin. Calcium reduced the anti‐thrombin activities of all the heparin preparations studied about 1 × 5 times when purified ATIII was used, although in plasma this effect was less clear. Consequently, in the presence of 1.5 mM calcium the ratio of the anti‐factor Xa to the anti‐thrombin activities of UF standard heparin approximated those of the LMW heparins. The only exception was CY222, which under all conditions retained anti‐factor Xa/anti‐thrombin ratios significantly higher than those of UF standard heparin.