bluuebunny/crossref_metadata_2025_split huggingface dataset:
Erythropoiesis in multiple myeloma: defective red cell production due to inappropriate erythropoietin production
Authors: Beguin Yves , Yerna Michèle , Loo Martine , Weber Mireille , Fillet Georges 
Published: March 2008

SummaryWe investigated the pathophysiology of erythropoiesis in 62 patients with multiple myeloma and examined whether it would establish a rational basis for the treatment of their anaemia with recombinant human erythropoietin. Erythropoietin (Epo) production was evaluated by serum levels and erythropoiesis was quantitated by serum transferrin receptor (TfR) levels. both assessed relative to the degree of anaemia. Instead of the expected stimulation of erythropoiesis in response to anaemia. haematocrit correlated positively with marrow erythropoietic activity. indicating that the mechanism of anaemia was primarily defective red cell production. Erythropoiesis decreased and anaemia worsened significantly with advancing clinical stage. 2 5% of the patients had inadequate Epo production and this proportion increased to 50% in stage 3. Inappropriate Epo production was seen in 60% of patients with renal impairment but was also observed in a number of patients with normal renal function. Erythropoiesis correlated strongly with the adequacy of Epo production particularly in advanced disease. Ve conclude that most myeloma patients have defective red cell production even in the absence of massive marrow infiltration and that inappropriate Epo production contributes to their anaemia.
Constitutive expression of IL‐1β, M‐CSF and c‐fms during the myeloid blastic phase of chronic myelogenous leukaemia
Authors: Specchia Giorgina , Liso Vincenzo , Capalbo Silvana , Fazioli Francesca , Bettoni Stefania , Bassan Renato , Viero Piera , Barbui Tiziano , Rambaldi Alessandro 
Published: March 2008

Summary.During the myeloid blast crisis (BC) of chronic myelogenous leukaemia (CML) non‐random additional chromosome abnormalities occur in over 80% of patients. However, these cytogenetic changes have been reported to precede the clinical signs of CML‐BC by several months to years suggesting that other biological events may participate in the multistep process of acute transformation of CML. The autocrine production of growth factors has been recently shown to occur in several haematological malignancies and particularly in acute myeloblastic leukaemia (AML). In the present report we demonstrate that IL‐1β gene is expressed in almost all cases of CML in myeloid blast crisis. The secretion of IL‐1 from CML blasts in culture supernatants was confirmed in all five of the patients we studied. A high proportion of cases showed constitutive expression of the M‐CSF gene and many of the same patients often had a simultaneous co‐expression of the proto‐oncogene c‐fms which encodes for the M‐CSF receptor. After exposure of leukaemic cells to phorbol myristate acetate (PMA), release of M‐CSF protein was documented in three of five patients studied. No significant interleukin‐3 (IL‐3), granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) or granulocyte colony‐stimulating factor (G‐CSF), was detected in these patients demonstrating that a different pattern of growth factors secretion exist in AML and CML, where distinct molecular events are likely involved in the control of leukaemic proliferation.
Autotransplantation of peripheral blood stem cells mobilized by chemotherapy and recombinant human granulocyte colony‐stimulating factor in childhood neuroblastoma and non‐Hodgkin's lymphoma
Authors: Fukuda Minoru , Kojima Seiji , Matsumoto Kimikazu , Matsuyama Takaharu 
Published: March 2008

Summary.Seven children with advanced neuroblastoma and non‐Hodgkin's lymphoma were treated with myeloablative chemoradiotherapy (180 mg/m2 melphalan plus 12 Gy fractionated total body irradiation), followed by autotrans‐plantation of peripheral blood stem cells (PBSC). Sufficient PBSC to restore bone marrow function were collected by a small number of leukaphereses during haematopoietic recovery after chemotherapy and recombinant human granulocyte colony‐stimulating factor (rhG‐CSF). Furthermore, rapid recovery of neutrophils was found in all patients by the administration of rhG‐CSF following transplantation: median 10 d (range 8–12) to attain more than 0.5 × 109/1 neutrophils, and 27 d (range 14–73) to attain more than 50 × 109/1 platelets, respectively. Haematopoietic reconstitution has been maintained throughout the follow‐up period (median 15 months; range, 6–22). Peripheral blood stem cells mobilized by chemotherapy and rhG‐CSF can induce complete haematopoietic reconstitution after myeloablative chemoradiotherapy.
Intramuscular anti‐D immunoglobulins for home treatment of chronic immune thrombocytopenic purpura
Authors: Gringeri Alessandro , Cattaneo Marco , Santagostino Elena , Mannucci Pier Mannuccio 
Published: March 2008

Summary.To assess the efficacy of home treatment with intramuscular anti‐D immunoglobulins (anti‐D IgG) in patients with idiopathic or HIV‐related chronic immune thrombocytopenic purpura (ITP), we conducted an open label, non‐controlled, prospective study with a follow‐up of 6 months in 51 consecutive patients with HTV‐related (n= 24) or idiopathic ITP (n= 27). Anti‐D IgG (13 μg/kg) were infused intravenously for three consecutive days (induction therapy). Patients whose platelet counts tailed to increase above 50 × 109/l were given a second course of the same therapy. If their platelet counts remained lower than 50 × 109/l, they were considered non‐responsive. Patients who responded to induction therapy were injected intramuscularly with 6 μg/kg/week anti‐D IgG if platelets were between 50 and 100 × 109/l or 13 μg/kg/week if they dropped to less than 50 × 109/l. After induction therapy, responses occurred in 20/24 HIV‐related chronic ITP patients (83%) and in 14/27 idiopathic chronic ITP patients (52%). During follow‐up, platelets remained above 50 × 109/l in 17/20 HIV‐related chronic ITP patients (85%) and in 8/14 (57%) idiopathic chronic ITP patients. We conclude that anti‐D IgG are a valid therapeutic option for treatment of idiopathic and HIV‐related chronic ITP, since they are safe, cheap and can be given intramuscularly at home.
Two distinct patterns of glycosylphosphatidylinositol (GPI) linked protein deficiency in the red cells of patients with paroxysmal nocturnal haemoglobinuria
Authors: Hillmen Peter , Hows Jill M. , Luzzatto Lucio 
Published: March 2008

Summary.We have studied three glycosylphosphatidylinositol (GPI) linked proteins on the erythrocytes of 14 patients with paroxysmal nocturnal haemoglobinuria (PNH). The pattern observed was bimodal in 12 of the patients and trimodal in two. Ten patients had a red cell population with normal CD59 antigen (membrane inhibitor of reactive lysis, MIRL), decay accelerating factor (DAF or CD55) and lymphocyte function‐associated antigen (LFA‐3 or CD58) and a second abnormal PNH population with absent CD59 antigen, DAF and LFA‐3. The other two patients with a bimodal pattern had a red cell population with normal CD59 antigen, DAF and LFA‐3 and an abnormal population with reduced, but not absent, CD59 antigen and DAF. The LFA‐3 on the abnormal red cells in these two patients appeared to be only slightly reduced. The two patients with a trimodal pattern had a normal population, a population with reduced, not absent, CD59 antigen and DAF, and a population with complete absence of CD59 antigen, DAF and LFA‐3. The accuracy of the Ham test in estimating the proportion of red cells with the PNH defect in the two types of PNH was assessed. The case of one patient who appeared to be ‘rescued’ from severe aplastic anaemia by the development of PNH is described.
Evaluation of erythropoiesis after bone marrow transplantation: quantitative reticulocyte counting
Authors: Davies S. V. , Cavill I. , Bentley N. , Fegan C. D. , Poynton C. H. , Whittaker J. A. 
Published: March 2008

Erythroid regeneration is an important and separate element in the engraftment process in allogeneic and autologous bone marrow transplantation (alloBMT, autoBMT). Qualitative visual reticulocyte counting has proved inadequate in the evaluation of erythropoiesis after BMT but automated flow cytometry now allows the reliable quantitation of reticulocytes even to very low levels. Reticulocyte counts and highly fluorescent reticulocyte (HFR) counts (very early reticulocytes) were estimated daily in recipients of 22 autoBMT and 14 alloBMT using a Sysmex R‐1000 automated reticulocyte counter. Marrow ablation caused an immediate and rapid fall in both the reticulocyte count and the HFR. Measurable numbers of reticulocytes persisted throughout the hypoplastic period, but HFR fell to zero in the majority of both the autoBMT and alloBMT. HFR rose significantly after a median time of 14 d post‐autoBMT, and 12 d post‐alloBMT. Attainment of 15 × 109/l reticulocytes and 0·5 × 109/l HFR at day 21 post‐transplant was associated with ultimate engraftment in 100% cases. Inadequate engraftment was seen in the majority of patients whose responses fell below these levels. Graft‐versus‐host disease was associated with a transient slight reduction in reticulocyte count. Neither episodes of infection nor blood transfusions had any significant impact on trends of reticulocytes or HFR.Automated flow cytometric reticulocyte counting has been shown to provide an accessible measure of erythroid activity which may be of predictive value in the management of patients following bone marrow transplantation.
Expression of multidrug resistance gene mdr1 mRNA in a subset of normal bone marrow cells
Authors: Marie Jean‐Pierre , Brophy Nathalie A. , Ehsan Mohamed N. , Aihara Yukoh , Mohamed Named A. , Cornbleet Joanne , Chao Nelson J. , Sikic Branimir I. 
Published: March 2008

Summary.The multidrug resistance gene mdr1, encoding P‐glycoprotein (P‐gp), can be expressed at high levels in tumour cells derived from normal tissues with constitutive high expression of this gene. In myelogenous leukaemia, the incidence of increased expression of mdr1 gene contrasts with the low expression of this gene in normal bone marrow (b.m.). To detect cells expressing mdr1 gene in normal and post‐chemotherapy b.m., we used in situ RNA hybridization and RNA phenotyping by the polymerase chain reaction for mdr1 mRNA detection. The presence of P‐gp was evaluated by immunocytochemistry with MRK16. Fifteen b.m. (eight normal and seven post chemotherapy) were tested by in situ hybridization and either PCR (three b.m.) or immunocytochemistry (11 b.m.) or both (one b.m.). With in situ mRNA hybridization, a subset (7.7%×3.1%) of b.m. cells expressed mdr1 mRNA in all cases tested, with no significant differences between normal b.m. and post chemotherapy b.m. 18% of myeloid recognizable cells and 7% of the cells with lymphoid morphology expressed mdr1 mRNA. By RNA phenotyping, the four samples tested for in situ hybridization and two additional post chemotherapy b.m. expressed mdr1. MRK16 was unable to detect a significant number of cells expressing P‐gp either by immunocytochemistry in the 12 b.m. tested for in situ hybridization (0% in nine cases; 0.4%, 1% and 3% of positive cells in three cases), or by flow cytometry in six additional normal b.m. (0–1.4% positive cells).
Abnormal CD45R expression in patients with common variable immunodeficiency and X‐linked agammaglobulinaemia
Authors: Richards Stephen J. , Scott Colin Stephen , Cole June C. , Gooi H. C. 
Published: March 2008

Summary.This study has investigated the patterns of membrane 2H4 (CD45RA) andUCHL1 (CD45RO) expression by CD4+ and CD8 + lymphocyte subpopulations in 10 adults and seven children with common variable immunodeficiency (CVI) and X‐linked hypogammaglobulinaemia (XLA). Of the 10 adults (CVI, n= 8; XLA, n= 2), only one with a diagnosis of CVI showed normal CD45R expression. For the remaining seven adult CVI patients the abnormal CD45R profiles were primarily associated with CD4+ lymphocytes in three and CD8+ lymphocytes in four. Specific increases in CD45RA‐CD45RO+ fractions were found in four CVI patients and in all of these there was a concomitant reduction in circulating CD19+ B‐cell numbers. Two of the CVI cases were identical twin sisters and both had the same CD45R abnormality. The two adults with XLA also showed abnormal CD45R expression (increased CD45RA+CD45RO∼ components) but of particular note, in view of the fact that these were brothers, one was associated with the CD4+ subpopulation and the other with the CD8+ fraction. Similar analyses for the paediatric group revealed, in distinct contrast to the adult patients, no significant abnormalities of CD45R expression suggesting that these defects may not become apparent until a later age. Further investigations of in vitro lymphocyte proliferation (PHA and PWM) in the eight adults with CVI showed a significant correlation between abnormal responses and disordered CD45R expression. It is proposed that these abnormal patterns of CD45R expression by lymphocyte subpopulations in CVI and XLA may be of fundamental importance with respect to the pathogenesis of these particular immunodeficiencies.
The value of detecting surface and cytoplasmic antigens in acute myeloid leukaemia
Authors: Urbano‐Ispizua Alvaro , Matutes Estela , Villamor Neus , Sierra Jorge , Pujades Asumpció , Reverter Joan‐Carles , Feliu Evarist , Cervantes Francisco , Vives‐Corrons Joan‐Lluis , Montserrat Emilio , Rozman Ciril 
Published: March 2008

Summary.The immunophenotype of leukaemia cells from 60 patients with acute myeloid leukaemia (AML) was analysed with the APAAP technique using a panel of anti‐myeloid and lymphoid associated monoclonal antibodies (McAb). Cells from all cases, including three with negative cytochemical features, were labelled by at least one of the anti‐myeloid McAb CD13, anti‐myeloperoxidase (anti‐Mpo), and/or CD14. The most sensitive marker was GD13, since it was positive in 90% of cases. In two out of three AML cases defined as MO‐AML, CD13 was expressed in the cytoplasm but not on the membrane; in these three cases peroxidase (Mpo) was not detected by conventional cytochemistry, but could be demonstrated in all of them using the McAb anti‐Mpo. The simultaneous expression of GD14 and CD68 McAb was often confined to the M4 and MS FAB AML subtypes (92% cases) as compared to the others: Ml, M2, M3 (18% cases). Lymphoid antigens were rarely positive (TdT +: 13%, CD7 +: 15%, CD19 +: 5%) and none of the AML cases were CD3+ or CD10 +. By contrast, CD4 was expressed in blasts from 44% of cases and this was not restricted to AML with a monocytic component (M4, M5) but also found in other subtypes. There were no significant differences in the clinical or prognostic features according to the positivity or negativity with TdT and CD4. By contrast, expression of CD7 was associated with refractoriness to the treatment or short complete remission duration, although the number of patients is too small to draw firm conclusions. Our findings support the clinical and diagnostic relevance of immunophenotypic studies in AML.
Monitoring circulating B cells in patients with multiple myeloma at diagnosis or in plateau phase: how prevalent is light chain isotype suppression?
Authors: King Malcolm A. , Radicchi Monica A. 
Published: March 2008

Summary.Peripheral blood lymphocytes from 25 patients with multiple myeloma at diagnosis or in plateau phase, and from 18 healthy subjects, were analysed for the surface expression of CD19 and immunoglobulin (Ig) light chain isotypes by dual parameter flow cytometry. The aim was to test for the existence of light chain isotype suppression (LCIS). LCIS is a hypothetical suppressor mechanism which supposedly operates in myeloma patients with stable disease, causing a drop in the number of circulating B cells bearing the same Ig light chain isotype as the myeloma paraprotein. Our experiments emphasized that the use of a non‐Ig, pan‐B cell marker, combined with dual antigen analysis, is necessary to distinguish Ig on B cells from (cytophilic) Ig on some non‐B cells. We found good correlation between results obtained using polyclonal versus monoclonal anti‐light chain antibodies, and washed blood versus peripheral blood mononuclear cells. There was no evidence of an abnormal ratio of CD19+, K+ to CD19+, λ+ cells in any of the patients. Thus, these patients did not manifest LCIS, and these experiments raise doubts about the existence of this phenomenon. The results also illustrate the problem that may arise in the interpretation of one parameter flow cytometry.
Measurement of free kappa and lambda chains in serum and the significance of their ratio in patients with multiple myeloma
Authors: Nelson M. , Brown R. D. , Gibson J. , Joshua D. E. 
Published: March 2008

Summary.An inhibition enzyme‐linked immunoassay technique using commercially available antibodies has been developed for the quantitation of both kappa and lambda light chains in the serum of patients with B‐cell malignancies. Assay conditions were selected to enable measurement of free light chains in the concentration range between 0.1 and 20 mg/1. The normal range for free lambda chains in serum was found to be 0.4–4.2 mg/1 and for free kappa chains it was 1.6–15.2 mg/1. At diagnosis the serum of most patients with multiple myeloma contained increased levels of the malignant free light chain and in some cases there was also elevation of the non‐malignant light chain. The absolute level of the malignant light chain at diagnosis did not correlate with survival nor with laboratory parameters such as IgM or creatinine. A correlation with β2M and serum paraprotein levels was evident only in cases of IgA myeloma. Although the absolute level of free serum light chain had no value as a prognostic indicator, the ratio of kappa: lambda chains closely followed the clinical assessment of disease status, being near the normal range (1.2–9.1) in plateau phase or stable disease. During periods of progressive disease this ratio ranged from 19 to 460 (n=14) in patients with kappa myeloma, and 0.0013–0.14 (n= 9) in patients with lambda myeloma. Determination of the ratio of free light chains in the serum may allow effective monitoring and earlier warning of disease progression in patients with multiple myeloma.
Rapid detection of a protein C gene mutation present in the asymptomatic and not in the thrombosis‐prone lineage
Authors: Bernardi F. , Patracchini P. , Gemmati D. , Boninsegna S. , Guerra S. , Legnani C. , Ballerini G. , Marchetti G. 
Published: March 2008

Summary.The presence of mutations in the serine protease domain of protein C was investigated by temperature gradient gel electrophoresis of PCR products in five patients with protein C deficiency and thrombosis. Molecules with an altered melting behaviour were detected in one subject with a history of venous and arterial thrombosis. Direct sequencing showed that a G deletion, present in the heterozygous state, caused a reading frame shift at Trp 300 and subsequently a premature termination at the codon 335. The resulting suppression of the protein C catalytic function explains the reduction of protease activity to half. In addition the mutation caused a reduction of the antigen level in plasma. Temperature gradient gel electrophoresis enabled the rapid detection of the gene alteration in the family of the propositus. Several members of the paternal lineage had had severe thrombotic episodes. Unexpectedly the mutation was found to be inherited from the clinically asymptomatic maternal lineage, thus suggesting that an additional unknown defect from the paternal lineage is present in the thrombosis‐prone propositus.
The in vitro effect of high‐dose recombinant human erythropoietin on granulocyte‐macrophage colony production in premature infants using a defined serum deprived cell culture system
Authors: Ward C. S. , Westwood N. B. , Emmerson A. J. B. , Pearson T. C. 
Published: March 2008

Recent reports of neutropenia associated with the use of recombinant human erythropoietin (r‐HuEpo) in preterm infants with the anaemia of prematurity have raised concern over the clinical use of this hormone. The present studies were undertaken to determine whether high‐dose r‐HuEpo has an effect on granulocyte production in vitro. The studies used a serum deprived, optimized semi‐solid cell culture system to investigate the effect of lineage specific and non‐specific granulocyte and erythroid colony stimulating factors on circulating peripheral blood granulocyte‐macrophage colony forming units (CFU‐GM), erythroid burst forming units (BFU‐E) and multilineage colonies (CFU‐Mix) from nine premature infants and seven healthy adults. CFU‐GM were grown in the presence of interleukin 3 (IL3) 8 ng/ml, granulocyte‐macrophage colony stimulating factor (GM‐CSF) 20 ng/ml and granulocyte colony stimulating factor (G‐CSF) 15 ng/ml alone and combinations of G‐CSF with GM‐CSF or IL3. The number, size and differentiation of CFU‐GM colonies were then analysed in the presence and absence of high dose r‐HuEpo (4 U/ml).High‐dose r‐HuEpo did not exert any significant modulatory effects on the number of CFU‐GM colonies produced in the presence of IL3, GM‐CSF and G‐CSF alone or in combination. The number of cells within each CFU‐GM colony did not change significantly, nor was there a significant change in the degree of differentiation. The combined number of BFU‐E. CFU‐GM and CFU‐Mix colonies increased with r‐HuEpo in both adults (1·8x) and preterm infants (1·4x), almost exclusively due to an increase in BFU‐E derived colonies. Thus, no evidence was found for an r‐HuEpo mediated redirection of multipotential haemopoietic stem cells into committed erythroid precursors at the expense of myeloid precursors.
Human parvovirus B19 in clotting factor concentrates: B19 DNA detection by the nested polymerase chain reaction
Authors: Zakrzewska K. , Azzi A. , Patou G. , Morfini M. , Rafanelli D. , Pattison J. R. 
Published: March 2008

The presence of B19 parvovirus in plasma from blood donors is seldom demonstrable, but clotting factor concentrates, prepared from large plasma pools, may be able to transmit B19 virus infection, and the effectiveness of different chemical and physical treatment to inactivate this virus is not yet known.In this study we report on the detection of B19 DNA in 25 clotting factor concentrates, prepared by a variety of procedures of purification and inactivation; dot blot hybridization and Southern blot hybridization assays, as well as a ‘nested’polymerase chain reaction (PCR) have been employed. Nine out of 25 products were B19 DNA positive by PCR, whereas only two gave positive results by hybridization techniques. B19 DNA positive concentrates have been found in ‘untreated’products but also in some solvent/detergent or steam‐treated products and even in monoclonal purified concentrates.PCR may be useful for the screening of blood products to be used in immunocompromised haemophiliacs, particularly in HIV positive subjects, at risk of severe chronic anaemia following B19 infection.