bluuebunny/crossref_metadata_2025_split huggingface dataset:
Argyrophilic nucleolar organizer region counts and prognosis in multiple myeloma
Authors: Pich A. , Marmont F. , Chiusa L. , Cappello N. , Resegotti L. , Navone R. 
Published: March 2008

The prognostic significance of argyrophilic nucleolar organizer regions (AgNORs) has been evaluated in bone marrow trephine biopsies from 64 patients with multiple myeloma (MM) prior to therapy.The univariate Kaplan‐Meyer survival analysis showed a significant correlation between survivals and AgNOR counts (median of survival 51.3 months for cases with 4.62 AgNORs per plasma cell (PC) versus 16 months for cases with >4.62 AgNORs per PC;P=0.0000) or AgNOR distribution in PC nucleus (AgNOR configuration) (median of survival 71.67 months for cases with tightly grouped AgNORs. 16.26 for partially grouped and 11.74 for dispersed AgNORs;P=0.001).Significant prognostic correlations were also found for monoclonal immunoglobulin type (P=0.008), platelet counts (P=0.0078). serum creatinine level (P=0.0001), Durie's clinical stage (P=0.02). percentage of plasma cells in bone marrow biopsies (BMPCX) (P= 0.005), pattern of medullary involvement (P=0.003) and PC atypia (P= 0.009). Borderline result was detected for the percentage of PCs in aspirates (P=0.06). No significant correlation was found between prognosis and patients age, sex, haemoglobin level, serum albumin or calcium level, marrow cellularity and excess of haemosiderin.Multivariate survival analysis showed that only two variables were significantly correlated with prognosis: AgNOR counts (P=0.003) and AgNOR configuration (P<0.001).In addition, the analysis of variance showed significant association between AgNOR number and platelet counts, haemoglobin level, calcaemia. creatininaemia, clinical stage, percentage of PCs in aspirates, BMPC%, pattern of medullary involvement, PC atypia, marrow cellularity and configuration of AgNORs.Our results indicate that AgNOR counts and configuration have prognostic and diagnostic value and therefore they are useful independent parameters to assess the pretherapeutic aggressiveness of multiple myeloma.
Endogenous platelet fibrinogen: its modulation after surface expression is related to size‐selective access to and conformational changes in the bound fibrinogen
Authors: Gralnick Harvey R. , Williams Sybil B. , McKeown Laurie , Shafer Brenda , Connaghan Gerard D. , Hansmann Kristin , Vail Michael , Magruder Louise 
Published: March 2008

Summary.Platelet stimulation results in the release of endogenous platelet fibrinogen which binds to the platelet surface. Previous studies have demonstrated that plasma fibrinogen bound to activated platelets becomes inaccessible to a variety of probes. We have studied endogenous platelet fibrinogen binding to activated platelets by employing an immunopurified polyclonal anti‐fibrinogen antibody and F26, a monoclonal anti‐fibrinogen antibody, which recognizes fibrinogen only when it is bound to a surface. Employing the Ig or F(ab')2of the poly‐ or monoclonal antibody we found a marked decrease of fibrinogen accessibility 30–60 min after platelet activation. In contrast, platelet‐bound fibrinogen remains accessible to the Fab fragment of F26 at a constant level for 30 min and increases at 60 min. The reduction of the polyclonal Fab fragment binding at 30 and 60 min is similar to the F26 Ig. These results indicate that the decreased accessibility of bound fibrinogen is related to two mechanisms; (1) that the access route to fibrinogen is size selective for the antibody probes and only small antibody probes, e.g. Fab fragments, can gain access to fibrinogen and (2) fibrinogen undergoes a conformational change(s) after binding which exposes at least one neo‐epitope in the D domain of fibrinogen and which may decrease or mask the reactivity of other fibrinogen domains. Only the F26 Fab probe has full access to and identifies fibrinogen present on the platelet surface 60 min after stimulation.
A patient with von Willebrand's disease characterized by a compound heterozygosity for a substitution of Arg by Gln in the putative factor‐VIII‐binding domain of von Willebrand factor (vWF) on one allele and very low levels of mRNA from the second vWF allele
Authors: Peerlinck Kathelijne , Eikenboom Jeroen C. J. , Ploos Hans K. , Amstel Van , Sangtawesin Wanida , Arnout Jef , Reitsma Pieter H. , Vermylen Jos , Brieut Ernest 
Published: March 2008

Summary.We describe a patient with a lifelong bleeding disorder previously classified as von Willebrand's disease (vWD) type I. The factor VIII (FVIII) level in this patient was disproportionately low and we showed that this was due to a decreased factor VIII binding capacity of her vWF. To characterize the molecular defect in this type of vWD, a cDNA‐dependent polymerase chain reaction (PCR) amplification was performed using platelet RNA as a template. Direct sequencing of the amplified fragment, which encodes for the FVIII‐binding domain, showed a single nucleotide change in exon 20 at codon 854, resulting in the substitution of CAG glutamine (Gln) for CGG arginine (Arg). At the level of the cDNA only the mutated sequence was found, whereas at genomic DNA level the patient was heterozygous for this mutation. This patient is therefore a compound heterozygote for a point mutation resulting in a FVIII‐binding defect and a vWF allele with low transcript levels.
Non‐radioactive in situ hybridization for the detection and monitoring of trisomy 12 in B‐cell chronic lymphocytic leukaemia
Authors: Cuneo A. , Wlodarska I. , Aly M. Sayed , Piva N. , Carli M. G. , Fagioli F. , Tallarico A. , Pazzi I. , Ferrari L. , Cassiman J. J. , Van Den Berghe H. , Castoldi G. L. 
Published: March 2008

Summary. Non‐radioactive in situ hybridization (NISII) with a chromosome 12‐specific alpha satellite probe was performed on 20 patients with chronic lymphocytic leukaemia (CLL) with normal karyotype (15 cases) or with inadequate mitotic yield (5 cases) from mitogen‐stimulated cultures.All patients had over 70% lymphocytes coexpressing the CD5/CD23 antigens. While less than 1% interphase nuclei showed three fluorescent spots in 16/20 patients, evidence of trisomy 12 in 15–25% interphase cells was detected in four patients. According to the FAB classification the diagnosis in these patients was typical B‐CLL, stage III (Rai's staging system) in one case, CLL/PLL, stage II and III in two cases, PLL, stage III in one case. In order to confirm these results, NTSH was repeated after 1 month in one patient and after 2 years in three patients. All patients had been treated with chemotherapy in the period between the two NISH experiments. In all cases a 1.8–3‐fold increase of percentage of trisomic interphase cells was detected.These findings suggest that in B‐CLL clones with trisomy 12 may have proliferative advantage over clonal B‐lymphocyte without +12 and possibly, that they may be more resistant to chemotherapy.We conclude that NISH is a sensitive technique allowing for the detection and monitoring of trisomy 12 in a fraction of B‐CLL patients with normal karyotype or with no analysable mitoses despite employment of polyclonal B‐cell mitogens.
Effects of anti‐TNF monoclonal antibody infusion in patients with hairy cell leukaemia
Authors: Huang David , Reittie Joyce E. , Stephens Susan , Hoffbrand A. Victor , Brenner Malcolm K. 
Published: March 2008

Summary.Tumour necrosis factor (TNF) can act as an autocrine growth factor for hairy cell leukaemia (HCL) cells. The TNF produced by the malignant clone may also inhibit normal haematopoiesis thereby contributing to the cytopenias observed in patients with the disease. We have studied the effects of infusing a murine monoclonal anti‐TNF antibody in three patients with HCL. In two patients receiving 0.5mg of antibody/kg on alternate days for 12 d, the drug was well tolerated. The third patient received 2 mg/kg on alternate days and developed symptoms of serum sickness by day 9. In two patients with severe B‐lymphocytopenia, circulating CD19 and CD20 positive, B‐cells were restored to normal, the majority of which were negative for the HCL‐associated marker CDllc. B‐lymphocyte recovery was associated with a rise in serum immunoreactive IL‐6 and with an early rise in immunoreactive TNF. These short courses of anti‐TNF MAb treatment had modest effect on the tumour burden, producing a reduction in splenomegaly in one patient. Exploration of the effects of more prolonged administration of higher dose anti‐TNF antibody will only be feasible when less immunogenic MAbs are available.
The presence of messenger RNA for HLA class I in human platelets and its capability for protein biosynthesis
Authors: Santoso Sentot , Kalb Rainer , Kiefel Volker , Mueller‐Eckhardt Christian 
Published: March 2008

Summary. In order to determine whether platelets contain specific messenger RNA encoding for HLA class I molecules, polymerase chain reaction (PCR) was performed with RNA from different platelet donors. Two amplified 300 bp and 279 bp cDNA fragments were obtained which encompassed sequences from 321 to 620 and from 795 to 1073. The 300 bp fragment encodes exon 2 and exon 3, the 279 bp encodes a portion of exon 4, exon 5, exon 6 and a portion of exon 7. A 300 bp nested PCR product from one donor, that encoded for the highly polymorphic region α2, was cloned and sequenced. The resulting nucleotide sequences fitted to the expected sequence for HLA B*3801 of this donor. Sequence analysis of the 279 bp PCR product demonstrated the presence of exon 5 encoding for the 117 bp transmembrane domain.In addition, de novo protein biosynthesis was studied by radioimmunoprecipitation of HLA class I molecules from 35S‐methionine metabolically labelled platelet lysates with a monoclonal antibody (mab) w6/32 specific for a monomorphic epitope on the heavy chain of HLA class I antigens. Analysis of the immunoprecipitates on SDS polyacrylamide gel electrophoresis showed a specific band with apparent molecular weight (Mr) of 44 kD corresponding to integral membrane HLA protein.On the basis of these results, we conclude that platelets contain specific messenger RNA encoding for HLA class I molecules and have the capability to synthesize the integral HLA membrane protein.
Antibodies against terminal galactosyl α(1–3) galactose epitopes in patients with idiopathic myelofibrosis
Authors: Leoni Pietko , Rupolj Serena , Salvi Aldo , Sambo Paola , Cinciripini Adriana , Gabrielli Armando 
Published: March 2008

Summary Sera from patients with myelofibrosis were analysed for circulating antibodies against an antigenic determinant characterized by two molecules of galactose in α 1–3 linkage (anti‐Gal antibodies).500% of patients were found to have values above the 90th percentile of the values of control sera chosen as a cut‐off. The median level of the antibodies was significantly higher than the value detected in normal controls, but no difference coulti be found between patients with idiopathic myelofibrosis and those with myelofibrosis associated to a chronic myeloproliferative disorder.Anti‐Gal antibodies were found to correlate with disease activity and with platelet count whereas no correlation was detected with other haematological parameters.Furthermore, for evaluation of disease activity, determination of serum anti‐Gal antibodies was a sensitive and specific parameter.We conclude that humoral immunity against Galα1–3Gal may provide a sensitive tool to detect disease activity in patients with idiopathic myelofibrosis and may be important for understanding its pathogenesis.
Diagnosis of paroxysmal nocturnal haemoglobinuria by phenotypLc analysis of erythrocytes using two‐colour flow cytometry with monoclonal antibodies to DAF and CD59/MACIF
Authors: Shichishima Tsutomu , Terasawa Takashi , Saitoh Yurie , Hashimoto Chokichi , Ohto Hitoshi , Maruyama Yukio 
Published: March 2008

Summary We investigated the relationship between the complement lysis sensitivity test and two‐colour flow cyto‐metric analysis using monoclonal antibodies to decay accelerating factor (DAF) and CD59/membrane attack complex inhibitory factor (MACIF) in patients with paroxysmal nocturnal haemoglobinuria (PNH) and other haematological diseases.Flow cytometry showed that all 59 PNH patients had two or three erythrocyte populations, while all 74 patients with other haematological diseases and all 31 healthy volunteers had a single erythrocyte population. We compared the percentage of PNH III erythrocytes in the lysis test with the percentage of negative cells shown by flow cytometry in 52 PNH patients, and found a significant correlation (r=0–960, P<0.001). However, in 13 patients the erythrocyte pheno‐types did not correspond in both tests. This was generally related to difficulty of detecting PNH II erythrocytes in the lysis test.In the PNH patients the ranges of mean fluorescence intensity for the negative, intermediate and positive erythrocyte populations were respectively 1.1–2.5. 2.2–29, and 61–600 for CD59IMACIF positivity and 1.9–7.2, 3.6–22, and 31–350 for DAF positivity. In contrast, the mean intensities in healthy volunteers ranged from 190 to 720 for CD59/ MACIF and from 150 to 350 for DAF.These findings suggest that PNH can be diagnosed and phenotypic analysis of PNH erythrocytes can be performed by respectively assessing the fluorescence profiles and mean fluorescence intensities of both proteins using flow cytometry. Flow cytometry may provide a superior diagnostic method to the traditional tests for PNH.
Hairy cell leukaemia: descriptive epidemiology and a case‐control study
Authors: Staines A. , Cartwright R. A. 
Published: March 2008

Summary The descriptive epidemiology of hairy cell leukaemia is reported from a specialized register of haematological malignancies covering approximately one‐third of England and Wales. The overall incidence of hairy cell leukaemia at 2.9 per million persons per year is similar to that recorded in America. There is a marked male preponderance (4.0 compared with 1.7 per million per year for females).A case‐control study on hairy cell leukaemia was conducted in the Yorkshire and Trent Regional Health Authority areas. 50 cases and 95 controls were identified, and interviewed using a structured questionnaire. Previous results on the aetiology of hairy cell leukaemia were not supported by this study, with the exception of an association between hairy cell leukaemia and exposure to organic solvents, petrochemicals and related products.
Lack of evidence for a role of HCV in hepatitis‐associated aplastic anaemia
Authors: Pol Stanislas , Thiers Valérie , Driss Françoise , Devergie Agnès , Berthelot Pierre , Bréchot Christian , Gluckman Eliane 
Published: March 2008

Summary Hepatitis‐associated aplastic anaemia (HAAA) is usually related to non‐A, non‐B hepatitis agents but the prevalence of anti‐hepatitis C virus (HCV) antibodies is similar in HAAA and aplasia of other origins according to the results of the ELISA1 assay. This fact could reflect either that HCV is not involved in HAAA or that HAAA‐associated defective immune function could yield false negative assays despite on‐going HCV infection.To test these hypotheses, we compared 19 patients with HAAA, including three ELISAl‐positive, to 23 patients with aplasia of known and unknown origin, including eight ELISA1‐positive. who were matched for age, sex and blood transfusion units. HCV infection was searched for by the second‐generation recombinant‐immunoblot assay (RIBA2), and by the polymerase chain reaction which detects HCV viraemia. HCV viraemia was detected in four among the 19 patients with HAAA and in six among the 23 patients with aplasia of other causes.HCV does not clearly appear responsible for hepatitis‐associated aplastic anaemia which could be due to non‐A. non‐B, non‐C hepatitis virus. HCV viraemia is frequent in severe aplastic anaemia, even without detectable anti‐HCV antibodies, and reflects mainly transfusion‐associated HCV infection.
Treatment of aplastic anaemia (AA) with antilymphocyte globulin (ALG) and methylprednisolone (MPred) with or without androgens: a randomized trial from the EBMT SAA working party
Authors: Bacigalupo A. , Chaple M. , Hows J. , Van Lint M. T. , McCann S. , Milligan D. , Chessells J. , Goldstone A. H. , Ottolander J. , van't Veer E. Th. , Comotti B. , Coser P. , Broccia G. , Bosi A. , Locasciulli A. , Catalano L. , Battista R. , Arcese W. , Carotenuto M. , Marmont A. M. , Smith E. C. Gordon 
Published: March 2008

Summary134 patients with acquired aplastic anaemia (AA) were given HALG 15 mg/kg/d for 5 d and methylprednisolone for 1 month, and randomized to receive (n= 69) or not (n= 65) oxymetholone 2 mg/kg/d p.o. daily for 4 months. Early mortality (<120 d) was comparable in the two arms 12/69 (17%) and 11/65 (17%), and correlated with the severity of the disease (39%, 10% and 6% respectively in patients with neutrophil counts (PMN) <0.2, 0.2–0.5, >0.5 × 109/l). The response rate at 120 d was significantly greater in patients receiving androgens (56%v40%;P= 0.04); it was 68%v48% (P= 0.02) in patients surviving 120 d, and 78%v27% (P= 0.03) in females with PMN less than 0.5 × 109/l. In a multivariate Cox analysis on patients with less than 0.5 × 109/l PMN, the probability of responding without androgens was reduced compared to the androgen treatment arm (P= 0.05).Survival was comparable in the two groups (71%v65%). It was superior (74%v50%), but not significantly (P= 0.1) in females with PMN 0.5 × 109/l receiving androgens.Side‐effects, including biochemical abnormalities and virilization, could be controlled and were reversible.In conclusion, the addition of androgens to HALG and methylprednisolone as first line treatment of aplastic anaemia significantly improves the response rate at 4 months, particularly in females with low neutrophil counts, although there is no significant effect on short‐term survival. The reversible side‐effects warrant the use of androgens as an adjunct to the first course of ALG in females with severe AA.
MDS‐macrophage derived inhibitory activity on myelopoiesis of MDS abnormal clones
Authors: Ohmori Seiichi , Ohmori Masami , Yamagishi Morihisa , Okuma Minoru 
Published: March 2008

Summary. We studied the effect of myelodysplastic syndrome (MDS)‐derived adherent cells on colony formation of granulocyte‐macrophage progenitors (CFU‐GM) in both normal and MDS bone marrow cells. MDS‐adherent cells suppressed the growth of normal CFU‐GM colony formation. Antibodies against ferritin almost totally neutralized the haematopoietic inhibitory activity. Antibody against gamma‐interferon (γ‐IFN) did not have such effect.By cytogenetic analysis using G‐staining method, MDS‐derived CFU‐GM colony showed abnormal clones. MDS have been recognized to be a mosaic of normal and abnormal clones. MDS‐macrophages suppressed the growth of progenitor cells derived from normal clones by soluble factors, but did not suppress the growth of those from abnormal clones. It is suggested that progenitor cells derived from abnormal clones are freed from the negative myelopoietic regulator that may be related to the progress of leukaemia.
The expression of cytokine and cytokine receptor genes in long‐term bone marrow culture in congenital and acquired bone marrow hypoplasias
Authors: Stark R. , Andre C. , Thierry D. , Cherel M. , Galibert F. , Gluckman E. 
Published: March 2008

Summary. A number of cytokines have been shown to have stimulatory activity on multipotent haematopoietic precursors. These include kit ligand (KL), interleukins (IL) 1, 3 and 6 and granulocyte macrophage‐colony stimulating factor (GM‐CSF). Using reverse transcriptase/polymerase chain reaction method (RT/PCR) we have examined the expression of these cytokines, the c‐kit and IL‐6 receptors, in long‐term bone marrow culture (LTC) adherent layer cells in human bone marrow hypoplasia syndromes.Disorders studied include Fanconi's anaemia (FA, n= 16), idiopathic aplastic anaemia (AA, n= 11), Seckel's syndrome (n= 2), dyskeratosis congenita (n= 2), Shwachman‐Diamond syndrome (n= 1), thrombocytopenia with absent radii syndrome (n= 1), acquired amegakaryocytosis (n= 1), paroxysmal nocturnal haemoglobinuria (n= 1) and acquired agranulocytosis (n= 1).IL‐6 and GM‐CSF expression appeared reduced in most patients with FA, suggesting that impaired production of these cytokines may contribute to the bone marrow failure seen in most patients with FA. In contrast, abundant IL‐6 and GM‐CSF expression were seen in most patients with AA when compared with the FA group and controls; these may be mediators of a stromal response in this disorder. No obvious differences were seen between the different patients’groups and controls in expression of the other cytokines or cytokine receptors studied.
Summarizing data on survival, relapse, and chronic graft‐versus‐host disease after bone marrow transplantation: motivation for and description of new methods
Authors: Pepe Margaret Sullivan , Longton Gary , Pettinger Mary , Mori Motomi , Fisher Lloyd D. , Storb Rainer 
Published: March 2008

Summary. Kaplan‐Meier curves are frequently used to summarize survival, relapse, and chronic graft‐versus‐host disease (GVHD) data in the bone marrow transplant setting. Some fundamental problems with the use of Kaplan‐Meier curves for the summary of relapse and GVHD are described.Alternatively, the use of simple probability and conditional probability curves for summarizing relapse incidence and transplant‐related mortality is illustrated with previously published data from a randomized clinical trial. Prevalence curves provide an appropriate alternative for the summary of a transient condition such as chronic GVHD. When combined with Kaplan‐Meier curves for survival and/or relapsefree survival, these methods provide a more accurate and comprehensive summary of the various marrow transplant outcomes.These methods of display are also applicable to other settings where more than one type of treatment failure can occur and where follow‐up time may be variable.
Treatment of primary refractory and relapsed acute lymphoblastic leukaemia in children and adults: the GIMEMA/AIEOP*experience
Authors: Giona Fiorina , Testi Anna Maria , Annino Luciana , Amadori Sergio , Arcese William , Camera Andrea , Di Montezemolo Luca Cordero , Ladogana Saverio , Liso Vincenzo , Meloni Giovanna , Moleti Maria Luisa , Rondelli Roberto , Zanesco Luigi , Pession Andrea , Mandelli Franco 
Published: March 2008

One hundred and forty‐seven patients aged <55 years with advanced acute lymphoblastic leukaemia (ALL) were enrolled in an Italian cooperative study (ALL R‐87), This protocol consists of an induction phase with idarubicin (IDA) plus intermediate‐dose cytarabine (IDARA‐C), followed by a consolidation phase and bone marrow transplant (BMT). Complete remission (CR) was achieved in 97/147 patients (66%) with a CR rate of 77% in children versus 51% in adults (P<0·01), 48 responders (50%) underwent BMT.Probability of event‐free survival (EFS ± SE) was 10·2±3·1% at 56 months. EFS was 14·3±4·51% at 56 months for children versus 3·8±3·41% at 37 months for adults (P<0·0001). Among patients treated in first relapse, EFS was 14·2±7·79% for patients with CR >18 months versus 6·6±3·17% for those with CR <18 months (P<0·0001).Projected disease‐free survival (DFS ±SE) was 15·4±4·61% at 55 months for all responders and 43·3±14·34% at 52 months for allografted patients. Projected overall probability of survival ±SE for all patients was 18·8±4·13% at 56 months.This study confirms the efficacy of IDA plus IDARA‐C in poor‐risk ALL patients. A more intensive post‐remission therapy or alternative approach must be designed to improve long‐term results.