bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interaction of five globin gene abnormalities in a Cambodian family
Authors: Simpkins H. , Hill A. V. S. , Derry S. , Clegg J. B. , Weatherall D. J. 
Published: March 2008

SummaryMembers of a Cambodian family with an undiagnosed hypochromic, microcytic anaemia were found by haemoglobin and DNA analysis to have five interacting globin gene abnormalities. One child has Hb E and typical Hb H disease, while his mother has the form of Hb H disease associated with Hb Constant Spring interacting with Hb E. Quantitation of Hbs E and A2 by globin chain separation and triton/urea gel electrophoresis support the concept that Hb H/Constant Spring disease is a more severe form of α thalassaemia than Hb H disease. This family illustrates how the remarkably high prevalence of globin gene abnormalities in Southeast Asians can give rise to a series of atypical thalassaemic phenotypes, and how they can be defined by direct globin gene analysis.
The influence of oxygen tension on the long‐term growth in vitro of haematopoietic progenitor cells from human cord blood
Authors: Smith Sydney , Broxmeyer Hal E. 
Published: March 2008

SummaryGrowth of low density human cord blood cells in long‐term suspension culture was evaluated at incubation conditions of 5% carbon dioxide in ∼ 20% (normal incubator) oxygen tension or in 5% (low) oxygen tension. During the first 5 weeks there was no difference in the numbers of morphologically recognizable cells grown at either oxygen tension, while growth was superior from weeks 5 to 8 at ∼ 20% oxygen tension. For the first 5 weeks, growth of granulocyte‐macrophage progenitors (CFU‐GM) was superior at 5% oxygen tension during the long‐term and semi‐solid culture phases and least impressive in the long‐term and semi‐solid cultures incubated at ∼ 20% oxygen. This trend was reversed after 5 weeks and after 8 weeks there were no detectable CFU‐GM in suspension cultures at 5% oxygen while steady state levels of CFU‐GM were maintained for greater than 12 weeks in suspension cultures at ∼20% oxygen. Semi‐solid cultures for erythroid (BFU‐E) and multipotential (CFU‐GEMM) progenitors were incubated at ∼ 20% oxygen only. During the first 4 weeks, the growth of BFU‐E and CFU‐GEMM was superior at 5% oxygen during long‐term culture. Numbers of these cells decreased by week 5 and at this time growth was better in the long‐term cultures grown at ∼ 20% oxygen. By week 6, no BFU‐E or CFU‐GEMM were detectable. Thus, growth of cord blood at low oxygen tension gives an initial enhancement in output of progenitor cells, but this appears to be at the expense of continued production.
A murine monoclonal IgM antibody specific for blood group P antigen (globoside)
Authors: Kr. vondem Borne A. E. G. , Bos M. J. E. , Joustra‐Maas N. , Tromp J. F. , Van Wijngaarden‐du Bois R. , Tetteroo P. A. T. 
Published: March 2008

SummaryA murine monoclonal IgM erythrocyte antibody appeared to have anti‐P (anti‐globoside) specificity. The antibody was a relatively weak cold agglutinin, but a strong haemolysin and its reactivity with red cells was markedly enhanced by enzyme treatment. This antibody was used to study the cell and tissue distribution of globoside. Globoside was not only detectable on red cells and erythroblasts, but also on endothelial cells and on subsets of platelets, megakaryocytes and fibroblasts. It was not detectable on granulocytes, monocytes and most peripheral blood lymphocytes. Neither was it present on erythroblast precursors (CFU‐E, BFU‐E), pro‐erythroblasts or on the cells of the pro‐erythroblastic cell lines K562 and HEL. However, K562 cells expressed globoside when induced to mature into erythroblasts by sodium butyrate. Cells of patients with various leukaemias were also tested. A significant number of positively reacting cells was frequently (six out of 18) seen in cases with a CML blast crisis (CML‐BC) and rarely in AML (four out of 37 cases). In CML‐BC the P‐positive cells were probably erythroblasts and/or megakaryoblasts. Thus, globoside appeared to be an interesting marker in CML‐BC of the erythroblastic or mixed erythroblastic‐megakaryoblastic type.
Successful remission induction with deoxycoformycin in elderly patients with T‐helper prolymphocytic leukaemia
Authors: El’Agnaf M. R. , Ennis K. E. , Morris T. C. M. , Robertson J. H. , Markey Geraldine , Alexander H. D. 
Published: March 2008

SummaryTwo elderly patients with prolymphocytic leukaemia (PLL) of T helper phenotype were treated with the adenosine deaminase inhibitor— deoxycoformycin—and achieved remission. The first patient has remained in an unmaintained remission for over a year. The second patient, treated with a regime which produced less side effects, subsequently relapsed in skin and lymph nodes and died. In view of the rarity of this condition a multi‐centre assessment of the effectiveness of deoxycoformycin is indicated.T‐lymphocyte colony formation in both cases was found to be reduced. Co‐culture of the patients’lymphocytes with nonadherent mononuclear cells from normal individuals also showed inhibition of T‐colony formation indicating that lack of nutrients or accessory cells was not responsible for low T‐colony forming capacity.
Competitive survival/proliferation of normal and Ph1‐positive haemopoietic cells
Authors: Frassoni Francesco , Repetto Mario , Podestà Marina , Piaggio Giovanna , Raffo Maria Rita , Sessarego Mario , Bacigalupo Andrea , Marmont Alberto M. 
Published: March 2008

SummaryBone marrow (BM) cells from 10 patients with Ph1‐positive chronic granulocytic leukaemia (CGL) were placed in long‐term cultures in the presence of fetal calf serum (FCS) and horse serum (HoS), or in the presence of human AB serum. The long‐term cultures were started with three different cell combinations: (1) CGL BM cells (four cases), (2) CGL BM cells + normal BM cells (1:1 ratio) from an HLA identical sex‐matched sibling (five cases), (3) CGL BM cells + normal BM cells (1:1 ratio) from an HLA identical sex mismatched sibling (five cases). Cytogenetic studies were performed at weeks 0, 3, 4 and 5 of culture. The results of this study can be summarized as follows: (a) Ph1‐positive cells could be detected at any time of culture in all three of the described cell combinations; (b) a population of Ph1‐negative cells of patient origin could be detected after 3–5 weeks of culture; (c) there was a trend for a better survival of Ph1‐negative cells in cultures supplemented with FCS + HoS and, conversely, of Ph1‐positive cells in cultures containing human serum. These results warrant further studies on the possibility of manipulating survival and proliferation of normal and leukaemic cells by varying the culture conditions.
An association between chronic neutrophilic leukaemia and multiple myeloma with a study of cobalamin‐binding proteins
Authors: Lewis Michael J. , Oelbaum Maurice H. , Coleman Morton , Allen Steven 
Published: March 2008

SummaryTwo patients are described who had evidence of both multiple myeloma and chronic neutrophilic leukaemia at or near the time of presentation. Descriptions of five similar patients were found in the literature supporting an association between the two disorders. This association is further evidence of a link between myeloproliferative and lymphoproliferative disorders. Cobalamin‐binding studies of the plasma and neutrophils from one of these patients showed a gross elevation of plasma unsaturated TC I and abnormal neutrophils which contained TC I but not TC III.
Ph1 negative haematological chimaerism after marrow transplantation in Ph1 positive chronic granulocytic leukaemia
Authors: Vincent P. C. , Young G. A. R. , Singh S. , Atkinson K. , Biggs J. C. 
Published: March 2008

SummaryA 17‐year‐old girl with Philadelphia chromosome (Ph1) positive chronic granulocytic leukaemia (CGL) who has undergone two bone marrow transplants from her HLA identical brother is described. Following the second transplant, cytogenetic analysis of her bone marrow cells showed haematological chimaerism with equal numbers of normal male cells and Ph1 negative female cells indicating the probable eradication of the Ph1 positive clones with the retention of normal host stem cells.
Purification of haemopoietic progenitor cells from patients with chronic granulocytic leukaemia using Percoll density gradients and elutriation
Authors: Martin Hans , Hibbin Jill A. , Dowding Charles , Matutes Estela , Tindle Robert , Goldman John M. 
Published: March 2008

SummaryPurification of haemopoietic progenitor cells from chronic granulocytic leukaemia buffy coat preparations requires a multistep approach using complementary cell separation techniques. In this study Percoll density gradient centrifugation and centrifugal elutriation were used to isolate large numbers of immature progenitor cells. Percoll density gradients were valuable as a first separation step: CFU‐GM and CFU‐GEMM could be enriched 75‐fold in a light density fraction of d< 1mD056 g/ml and the technique could be adapted to cope with more than 1010 buffy coat leucocytes. Progenitors cells were concentrated 3‐fold by elutriation used as single method to separate buffy coat cells or when used to purify further light density Percoll fractions. When Percoll gradients and elutriation were used sequentially, undifferentiated mononuclear cells were enriched to more than 90% purity arid between 5% and 40% of these cells formed CFU‐GM or BFU‐E colonies consisting of more than 40 cells. The enriched fractions were further characterized with monoclonal antibodies. The density and elutriation profiles of these colony forming cells resembled corresponding profiles of cells that reacted with the monoclonal antibody BI‐3C5, which recognizes an antigen on primitive haemopoietic progenitor cells. Physical separation methods are a valuable first stage in the attempt to procure relatively pure myeloid progenitor cell populations, whose characteristics can then be further studied at a cellular or molecular level.
Autologous bone marrow transplantation (ABMT) for acute leukaemia in complete remission: a pilot study of 33 cases
Authors: Cahn J. Y. , Herve P. , Flesch M. , Plouvier E. , Noik A. , Racadot E. , Montcuquet P. , Behar C. , Plgnon B. , Boilletot. A. , Lutz P. , Henon P. , Rozenbaum A. , Peters A. , L econte Des Floris R. 
Published: March 2008

SummaryThirty‐three leukaemic patients in CR were treated by high‐dose therapy followed by ABMT: 18 of them had acute non‐lymphoblastic leukaemia (ANLL) in first remission (CR1) with a mean age of 23.7 years (3–44). All but one of them were conditioned with a polychemotherapy regimen including 6‐thioguanine, Ara‐C, CCNU, and cyclophosphamide. The marrow cells were purged by chemical means in 16 cases.
Molecular pathology of haemoglobin H disease in Sardinians
Authors: Paglietti E. , Galanello R. , Moi P. , Pirastu M. , Cao A. 
Published: March 2008

SummaryWe investigated the molecular basis for haemoglobin H disease in 50 Sardinian patients by restriction endonuclease analysis. We found that the majority (78% of the cases) are due to gene deletion (–/ ‐ α). Among those with a combination of deletion and nondeletion defects (–/ααth), the most prevalent nondeletion lesion (70% of the nondeletion defects) was the initiation codon mutation of the α2 gene (αNcoα), previously discovered in this population. Of the remaining patients with the (–/ααth) genotype, two showed the IVS‐1 splice junction lesion and one a mutation in the α1 gene, removing the Nco I site within the 5’part of the α1 gene, which may arise from a process of gene conversion from the initiation codon mutant of the α2 gene. A single patient had the homozygous state for the initiation codon mutant of the α2 gene. Study of genotype‐phenotype correlations indicates that the (αNcoα) haplotype is associated with a more severe defect in the α‐globin chain output than that resulting from the (‐α) haplotype. We may conclude that restriction endonuclease analysis is a powerful method for the definition of the molecular heterogeneity of haemoglobin H disease.
Acute myeloid leukaemia in childhood: clinical features and prognosis
Authors: Chessells Judith M. , Ocallaghan Una , Hardisty Roger M. 
Published: March 2008

SummaryClinical and laboratory features at presentation were correlated with morphological (FAB) subclass of AML in a group of 112 children diagnosed between 1972 and 1982. Patients with a monocytic component of AML (M4, M5) had higher initial leucocyte counts, a higher incidence of extramedullary infiltration and of CNS involvement. In M4 AML CNS relapse occurred in patients with a high initial leucocyte count whereas in M5 AML CNS involvement tended to occur at presentation in children with low initial counts. Two‐thirds of patients treated achieved remission and most failures were due to inadequate chemotherapy, although haemorrhage, leucostasis or metabolic complications caused early death in patients with M4 and M5 AML. With a minimum follow up of 3 years only 12% of patients are alive; these figures have not improved in consecutive series despite increasing intensity of induction and more recent availability of bone marrow transplantation. No features predictive of long‐term survival were identified, but patients with myeloid differentiation (M1, M2, M3) did better than those with a monocytic or erythroid component (M4, M5, M6).
Red cell metabolism in hereditary pyrimidine 5′‐nucleotidase deficiency: effect of magnesium
Authors: Lachant Neil A. , Tanaka Kouichi R. 
Published: March 2008

SummarySince pyrimidine nucleotides avidly bind magnesium, we tested the hypothesis that the haemolytic anaemia in hereditary pyrimidine 5′‐nucleoti∼ dase (P5N) deficiency is due to a state of functional magnesium depletion in the red cell (RBC). In haemolysates from normal subjects, cytidine triphos‐phate (CTP) inhibited the activity of pyruvate kinase in a competitive manner for magnesium. The CTP Ki was 0.4 mmol/1. CTP inhibited the activity of hexokinase in a competitive manner for ATP (Mg‐ATP2‐) with a Ki of 4 mmol/1. The inhibitory effect of CTP on both enzymes was overcome by increasing the magnesium content of the test system. Since CTP appeared to inhibit enzymes which required magnesium as a cofactor or Mg‐ATP2‐ as a substrate, we tested the effect of exogenous magnesium on the metabolism of P5N deficient RBC. The autohaemolysis test, the incubated Heinz body assay and the rate of glucose oxidation by the pentose phosphate shunt were abnormal in the intact RBC from a patient with hereditary P5N deficiency. The addition of MgCl2 (6–10 mmol/1) did not improve these abnormal in vitro measures of metabolism in the P5N deficient RBC. This lack of effect of exogenous magnesium may be due to the slow uptake of magnesium by the human RBC.
Reduced risk of recurrent leukaemia in bone marrow transplant recipients after cytomegalovirus infection
Authors: Löunnqvist B. , Ringdegn O. , Ljungman P. , Wahren B. , Gahrton G. 
Published: March 2008

SummaryThe first 72 consecutive bone‐marrow transplant recipients with haematological malignancies (29 with acute nonlymphoblastic leukaemia, 31 with acute lymphoblastic leukaemia, nine with CML and three with myelofibro‐sis, IgA myeloma and T‐cell lymphoma, respectively) were investigated for the frequency of relapses 1 year or later after bone‐marrow transplantation. Seven relapses occurred from 30 to 850 d after transplantation (median 180 d). All relapses occurred in patients with acute leukaemia ≤ 18 years of age with a high risk for relapse, i.e. transplanted in second or later remission or with more than 10% blasts in the marrow before transplantation. Among all patients the probability of relapse was increased in patients without cytomegalovirus (CMV) infection (P= 0.001) and in patients without chronic GVHD (P= 0.049). Among leukaemic patients ≤ 18 years of age with a high risk of relapse all relapses occurred in patients (n= 11) without CMV infection, whereas no relapses were seen in patients (n= 13) with CMV infection (P= 0.006). Known risk factors for leukaemic relapse were comparable in both groups.
Autoimmune thrombocytopenia and neutropenia after remission induction therapy for acute leukaemia
Authors: Chapman J. F. , Murphy M. F. , Minchinton R. M. , Metcalfe P. , Lister T. A. , Waters A. H. 
Published: March 2008

SummaryPatients with acute leukaemia who are exposed to intensive chemotherapy, with or without radiotherapy, may remain thrombocytopenic or neutropenic in remission. The incidence of these prolonged cytopenias was examined retrospectively in 46 patients in remission and prospectively in 14 patients. The patients were tested for the presence of autoantibodies to platelets and neutrophils using a fluorescent antihuman globulin technique with paraformaldehyde‐fixed cells. In the retrospective study nine patients (20%) had neutrophil autoantibodies and seven (15%) had platelet autoantibodies; only one of the former had neutropenia and one of the latter thrombocytopenia. In the prospective study three (21%) had neutrophil autoantibodies and seven (50%) had platelet autoantibodies. One of the patients with platelet autoantibodies had transient thrombocytopenia, and shortened platelet survival was demonstrated. None of the patients with neutrophil autoantibodies had neutropenia.The rare occurrence of cytopenias in association with these autoantibodies was possibly due to bone marrow compensation for antibody‐mediated cell destruction, although other possible mechanisms are discussed.
Von Willebrand factor contaminating porcine factor VIII concentrate (Hyate: C) causes platelet aggregation
Authors: Altieri Dario C. , Capitanio Anna M. , Mannucci Pier Mannuccio 
Published: March 2008

SummarySevere thrombocytopenia has been reported to occur in some patients treated with a polyelectrolyte‐fractionated porcine factor VIII concentrate (Hyate:C) (Kernoff et al, 1984; Gatti & Mannucci, 1984). We report here that Hyate: C induces aggregation of platelet‐rich plasma in vitro accompanied by ATP release and thromboxane B2 formation, and is inhibited by EDTA and prostaglandin E1. Hyate:C induced platelet aggregation is affected by monoclonal antibodies anti‐glycoprotein Ib or anti‐glycoprotein IIb/IIIa and suppressed by polyclonal anti‐porcine von Willebrand factor antiserum. We conclude that the aggregating ability of Hyate :C is due to porcine von Willebrand factor present in the concentrate. The occasional thrombocytopenia described after Hyate: C infusions probably results from the interaction between platelets and the porcine von Willebrand factor contaminating the concentrate.
Canine platelet alloimmunization: the role of donor selection
Authors: Slichter Sherrill J. , O'Donnell Margaret R. , Weiden Paul L. , Storb Rainer , Schroeder Maria‐Louise 
Published: March 2008

SummaryFive different platelet transfusion programmes were evaluated in a canine model to determine the most effective method of providing long‐term platelet support. When a weekly transfusion from a single unrelated donor was used, alloimmune platelet refractoriness developed in 95% of recipients after an average of 3.1 ± 0.7 transfusions, and donor platelets circulated for a total of 8.2 ± 2.3 d. When multiple unrelated donors were used, the percentage of refractory recipients was similar (60% versus 77%) whether platelets came from six single donors given sequentially or from a pool of the same six donors given repeatedly. There was, however, a significant difference in the number of transfusions given prior to immunization (14 ± 5 transfusions lasting 32 ± 12 d for sequential single donors as compared to 5.5 ± 1.0 transfusions lasting 13 ± 2 d for the pooled donors).
A stimulator of murine haemopoietic stem cell proliferation produced by human fetal liver cells
Authors: Cork Michael J. , Riches Andrew C. , Wright Eric G. 
Published: March 2008

SummaryNormal murine bone marrow was incubated with medium conditioned by liver cells from human fetuses of 11–17 weeks gestational age. This treatment increased the proportion of murine haemopoietic stem cells (CFU‐S) which were synthesizing DNA from less than 10% to more than 30%. The human fetal liver cell supernatants were fractionated using Amicon filters to obtain nominal molecular weight ranges of 10–30 000, 30–50 000 and 50–100 000 daltons. The stimulator was present only in the 30–50 000 dalton fraction. When human fetal liver cells were separated by adherence to plastic, medium conditioned by the adherent, but not the non‐adherent, cells produced the stimulator. A population of non‐cycling GM‐CFC was not switched into cycle during incubation with this CFU‐S proliferation stimulator. Human fetal livers of all gestational ages tested contain a specific stimulator of CFU‐S proliferation. This appears to have properties similar to that demonstrated in murine fetal liver and regenerating murine bone marrow. Human and murine haemopoietic stem cell proliferation may therefore be regulated by similar mechanisms.
In vitro and in vivo effects of treatment by platelet‐activating factor on N‐formyl‐met‐leu‐phe‐mediated responses of polymorphonuclear leucocytes
Authors: Ingraham Leah M. , Lafuze Joan E. , Boxer Laurence A. , Baehner Robert L. 
Published: March 2008

SummaryTwo chemoattractants, the peptide N‐formyl‐met‐leu‐phe (FMLP), and the ether phospholipid, platelet activating factor (PAF), each stimulate a variety of in vitro responses in polymorphonuclear leucocytes (PMN). Because often more than one inflammatory mediator is active during inflammation, we determined the effect on PMN of sequential stimulation with these two agents. Before FMLP stimulation, human PMN were exposed to PAF, at concentrations which gave little or no response when administered alone. PAF enhanced FMLP‐elicited superoxide release in a dose‐dependent fashion. Likewise, release of granular lysozyme from the cells was increased in PAF treated cells. Similar treatment with other phospholipids, including the lyso derivation of PAF, failed to produce these effects. Incubation with nordihydro‐guaiaretic acid, an inhibitor of arachidonic acid metabolism, had little effect on the enhancement of lysozyme release by PAF. To determine if enhancing effects by PAF might occur also in vivo, we studied rabbits receiving PAF and/or FMLP intravenously. When rabbits received 0·01 μg PAF (a dose which does not elicit the sustained neutropenia observed with higher doses of PAF) followed by 0·05 μg FMLP the absolute granulocyte count (AGC) dropped at 1 min (46 ± 11% of original value), and continued to fall (24 ± 12% at 10 min). Controls, treated with the suspending fluid for PAF, and then 0·05 μg FMLP, had a similar 1 min AGC value, but at 10 min AGC returned to 65±6·1% (P<0·001 for comparison of 10 min values). Thus PAF pretreatment enhanced FMLP‐elicited granulocytopenia in vivo. Study of in vitro human PMN aggregation revealed that, at certain relative concentrations of PAF and FMLP. aggregation was enhanced. These studies show that both in vitro and in vivo responses of FMLP‐stimulated PMN may be exaggerated by pre‐exposure to PAF.