bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ability of myeloma cells to secrete macrophage inflammatory protein (MIP)‐1α and MIP‐1β correlates with lytic bone lesions in patients with multiple myeloma
Authors: Hashimoto Toshihiro , Abe Masahiro , Oshima Takashi , Shibata Hironobu , Ozaki Shuji , Inoue Daisuke , Matsumoto Toshio 
Published: December 2004

SummaryMacrophage inflammatory protein (MIP)‐1α and MIP‐1β have been identified as candidates for multiple myeloma (MM)‐derived bone‐resorbing factors. To validate the clinical relevance of these observations, we investigated correlations between the ability of MM cells to secrete these chemokines and the extent of MM bone lesions as well as levels of biochemical bone markers in patients with MM. Patients with multiple bone lesions exhibited higher MIP‐1α and MIP‐1β secretion from MM cells along with elevated urinary deoxypyridinoline (Dpd), without significant elevation of serum bone‐specific alkaline phosphatase (BALP) or osteocalcin compared with those with minimal bone lesions. MIP‐1α and MIP‐1β levels correlated positively with urinary Dpd and serum BALP but not with serum osteocalcin. These results provide further evidence for a causal role of MIP‐1α and MIP‐1β in the development of lytic bone lesions, and suggest that MM cells suppress osteoblastic bone formation to cause an imbalance of bone turnover and development of destructive bone lesions.
Elevated levels of transferrin receptor 2 mRNA, not transferrin receptor 1 mRNA, are associated with increased survival in acute myeloid leukaemia
Authors: Nakamaki Tsuyoshi , Kawabata Hiroshi , Saito Bungo , Matsunawa Manabu , Suzuki Junko , Adachi Daisuke , Tomoyasu Shigeru , Phillip Koeffler H. 
Published: December 2004

SummaryTransferrin receptor 1 (TfR1) is a type II membrane protein that mediates cellular iron uptake. Transferrin receptor 2(TfR2), another receptor for transferrin (Tf), has recently been cloned. We examined expression levels of TfR1, TfR2‐α (membrane form) and TfR2‐β (non‐membrane form) transcripts in cells from 67 patients with de novo acute myeloid leukaemia (AML) using reverse transcription‐polymerase chain reaction (RT‐PCR), and correlated the results with a variety of clinical features and disease outcomes of these patients. Significant correlations were noted between the levels of both TfR1 and TfR2‐α (r = 0·771, P < 0·001) and TfR1 and TfR2‐β (r = 0·534, P < 0·001). Unexpectedly, initial white blood cell (WBC) counts were inversely correlated with levels of expression of either TfR1(r = −0·357, P = 0·003), TfR2‐α (r = −0·486, P < 0·0001), or TfR2‐β (r = −0·435, P = 0·0003). Only TfR2 expression was significantly associated with either serum iron (r = −0·270, P = 0·045) or serum ferritin (r = −0·364, P = 0·008). Multivariate analyses using Cox's proportional hazard model showed that elevated TfR2‐α, but not TfR1 or TfR2‐β mRNA levels significantly contributed to a better prognosis for AML patients. Furthermore, a group with high expression levels of both TfR2‐α and TfR2‐β survived significantly longer than a group without high expression of both of them (P < 0·01 by log‐rank). The present study suggests that (i) TfRs‐independent iron uptake might have an important role in in vivo proliferation of AML cells; (ii) expression of TfR2 (especially the α form) is a novel prognostic factor for patients with AML.
Analysis of histone deacetylase inhibitor, depsipeptide (FR901228), effect on multiple myeloma
Authors: Khan S. B. , Maududi T. , Barton K. , Ayers J. , Alkan S. 
Published: December 2004

SummaryMultiple myeloma (MM) is a neoplastic proliferation of plasma cells and remains an incurable disease because of the development of drug resistance. Histone deacytylase (HDAC) inhibitors are a new class of chemotherapeutic reagents that cause growth arrest and apoptosis of neoplastic cells. Depsipeptide, a new member of the HDAC inhibitors, was found to be safe in humans and has been shown to induce apoptosis in various cancers. In order to evaluate the effects of depsipeptide, a MM cell line, U266 [interleukin (IL)‐6 dependent], was analysed for viability and apoptosis. The combined effect of depsipeptide with melphalan and changes in BCL‐2 family proteins (BCL‐2, BCL‐XL, BAX and MCL‐1) were also investigated. In addition, the RPMI 8226 cell line (IL‐6 independent), and primary patient myeloma cells were also analysed for apoptosis after depsipeptide treatment. Depsipeptide induced apoptosis in both U266 and RPMI 8226 cell lines in a time‐ and dose‐dependent fashion, and in primary patient myeloma cells. We also demonstrated that depsipeptide had an additive effect with melphalan (10 μmol/l). BCL‐2, BCL‐XL and MCL‐1 showed decreased expression in depsipeptide‐treated samples. Based on recent clinical trials demonstrating minimal clinical toxicity, our study supports the future clinical utilization of depsipeptide in the management of MM.
CD90/Thy‐1 is preferentially expressed on blast cells of high risk acute myeloid leukaemias*
Authors: Buccisano Francesco , Rossi Francesca Maria , Venditti Adriano , Poeta Giovanni Del , Cox Maria Christina , Abbruzzese Elisabetta , Rupolo Maurizio , Berretta Massimiliano , Degan Massimo , Russo Stefania , Tamburini Anna , Maurillo Luca , Principe Maria Ilaria Del , Postorino Massimiliano , Amadori Sergio , Gattei Valter 
Published: December 2004

SummaryDifferent transformation mechanisms have been proposed for elderly acute myeloid leukaemia (AML) and secondary AML (sAML) when compared with de novo AML or AML of younger patients. However, little is known regarding differences in the immunophenotypic profile of blast cells in these diseases. We systematically analysed, by flow cytometry, 148 patients affected by de novo (100 cases) or sAML (48 cases). By defining a cut‐off level of 20% of CD34+ cells co‐expressing CD90, the frequency of CD90+ cases was higher in sAML (40%) versusde novo AML (6%, P < 0·001), elderly AML (>60 years) (24%) versus AML of younger patients (10%, P = 0·010) and poor‐ versus good‐risk karyotypes (according to the Medical Research Council classification, P < 0·001). The correlation between CD90 expression, sAML and unfavourable karyotypes was confirmed by analysing the subset of CD34+ AML cases alone (91/148). Consistently, univariate analysis showed that expression of CD90 was statistically relevant in predicting a shorter survival in CD90+ AML patients (P = 0·042). Our results, demonstrating CD90 expression in AML with unfavourable clinical and biological features, suggest an origin of these diseases from a CD90‐expressing haemopoietic progenitor and indicate the use of CD90 as an additional marker of prognostic value in AML.
Early response to therapy and survival in multiple myeloma
Authors: Schaar C. G. , Kluin‐Nelemans J. C. , le Cessie S. , Franck P. F. H. , te Marvelde M. C. , Wijermans P. W. 
Published: December 2004

SummaryWhether the response to chemotherapy is a prognosticator in multiple myeloma (MM) is still not known. Therefore, the relationship between survival and the rate of monoclonal protein (M‐protein) decrement during the first cycles of therapy was prospectively assessed in 262 patients with newly diagnosed MM that were included in a phase III trial (HOVON‐16). M‐proteins were collected monthly during melphalan–prednisone therapy (MP: melphalan 0·25 mg/kg, prednisone 1·0 mg/kg orally for 5 d every 4 weeks). Patients with light chain disease (n = 18), immunoglobulin M (IgM)‐MM (n = 1) and no immunotyping (n = 1) were excluded. Of the 242 patients studied, 75% had IgG M‐protein and 25% IgA; MM stages: I: 1%, II: 35% and III: 64%. The median M‐protein decrease after the first cycle of MP was 21% for IgG and 27% for IgA, and declined to < 5% after four cycles. An obvious survival advantage was seen for patients who had an M‐protein decrease of at least 30% after the first MP cycle, which became significant when an M‐protein decrease of 40% or more was reached. As established prognostic parameters (Salmon & Durie stage, serum creatinine, and haemoglobin) also remained prognostically significant, we concluded that early response to MP predicts for survival in MM.
Clinical impact of early absolute lymphocyte count after allogeneic stem cell transplantation
Authors: Kim Dong Hwan , Kim Jong Gwang , Sohn Sang Kyun , Sung Woo Jin , Suh Jang Soo , Lee Kun Soo , Lee Kyu Bo 
Published: December 2004

SummaryThe role of repopulating lymphocytes after allogeneic stem cell transplantation (SCT) includes the prevention of serious infections and attacking residual tumour cells in the early post‐transplant phase. Therefore, the current study analysed the role of the absolute lymphocyte count (ALC) on day 21 after SCT in predicting transplant outcomes of 82 patients in terms of the risk of opportunistic infections and recurrence of original disease. The median dose of CD34+, CD3+ and mononuclear cells (MNC) infused was 6·41 × 106/kg, 1·96 × 108/kg and 6·81 × 108/kg respectively. The high ALC group (high ALC on day 21; ≥0·35 × 109/l) was associated with the use of peripheral blood stem cells, matched sibling donors and higher cell doses of MNC, CD3+ and CD4+ cells. The high ALC group also exhibited a better overall survival (56·3% vs. 17·7%) and disease‐free survival (50·1% vs. 15·9%) after 3 years and lower incidences of relapse (33·6% vs. 67·1%) and fungal infections (3·0% vs. 19·5%) after 1 year. The incidence of cytomegalovirus antigenaemia was lower in the high ALC group (47·7% vs. 73·7%). Accordingly, identifying the ALC on day 21 would appear to be a useful and simple measurement to predict those patients with a high risk of opportunistic infections and relapse after allogeneic SCT.
Prospective clinical evaluation of a LightCyclerTM‐mediated polymerase chain reaction assay, a nested‐PCR assay and a galactomannan enzyme‐linked immunosorbent assay for detection of invasive aspergillosis in neutropenic cancer patients and haematological stem cell transplant recipients
Authors: Buchheidt Dieter , Hummel Margit , Schleiermacher Dietlind , Spiess Birgit , Schwerdtfeger Rainer , Cornely Oliver A. , Wilhelm Stefan , Reuter Stefan , Kern Winfried , Südhoff Thomas , Mörz Handan , Hehlmann Rüdiger 
Published: December 2004

SummaryInvasive aspergillosis (IA) is a considerable clinical problem in neutropenic patients with haematological malignancies but its diagnosis remains difficult. We prospectively evaluated a LightCyclerTM polymerase chain reaction (PCR) assay, a nested‐PCR assay and a galactomannan (GM) enzyme‐linked immunosorbent assay (ELISA) to validate their significance in diagnosing IA. During 205 treatment episodes in 165 patients from six centres, a nested‐PCR assay and GM testing was performed at regular intervals. Positive nested‐PCR results were quantified by a LightCyclerTM PCR assay. Patient episodes were stratified according to the 2002 European Organization for Research and Treatment of Cancer/Mycosis Study Group consensus criteria and the PCR and serology results were correlated with the clinical diagnostic classification. Sensitivity and specificity rates for the nested‐PCR assay were up to 63·6% [95% confidence interval (CI): 30·8–89%) and 63·5% (95% CI: 53·4–72·7%) respectively, and 33·3% and 98·9% (95% CI: 7·5–70·1% and 94·2–99·9%) for GM respectively. The LightCyclerTM PCR assay yielded positive results in 21·4%, lacking discrimination by quantification across the different clinical categories. In this prospective comparison, PCR was superior to GM with respect to sensitivity rates. In patients at high risk for IA, positive results for Aspergillus by PCR of blood samples are highly suggestive for IA and contribute to the diagnosis.
Establishment of a pluripotent preleukaemic stem cell line by expression of the AML1‐ETO fusion protein in Notch1‐immortalized HSCN1cl10 cells
Authors: Delaney Colleen , Bernstein Irwin D. 
Published: December 2004

SummaryThe AML1‐ETO fusion has been associated with up to 40% of acute myeloid leukaemia French–American–British classified M2 cases. This chimaeric protein interferes with normal AML1 function and disrupts critical transcriptional regulation of haematopoiesis. Current evidence suggests that AML1‐ETO alone is insufficient to induce leukaemia, but rather is a co‐operating event in leukaemogenesis. We developed a pluripotent murine haematopoietic stem cell line expressing the AML1‐ETO fusion protein that displays in vitro and in vivo properties consistent with a preleukaemic state, including inhibition of terminal granulocytic differentiation in vitro and the development of non‐lymphoid leukaemias in vivo. This cell line represents a potential platform for the introduction and in vitro rapid screening of candidate genes thought to co‐operate with AML1‐ETO in developing frank leukaemia.
Rituximab in the treatment of alloimmune factor VIII and IX antibodies in two children with severe haemophilia
Authors: Mathias Mary , Khair Kate , Hann Ian , Liesner Ri 
Published: December 2004

SummaryWe report the use of rituximab (Genentech, San Francisco, CA, USA) in two children with severe haemophilia with inhibitors to factors VIII and IX, which failed to respond to conventional immune tolerance therapy. The treatment was well tolerated by both children. The child with haemophilia B had no clinical improvement or fall in CD19 and he is currently being treated with recombinant activated factor VII (NovoSeven, Novo Nordisk, Denmark) for bleeding episodes. The child with haemophilia A had a good clinical response with a negative inhibitor assay at 11 months follow‐up.
The London Cord Blood Bank: analysis of banking and transplantation outcome
Authors: Davey Sue , Armitage Sue , Rocha Vanderson , Garnier Federico , Brown Juliette , Brown Colin J. , Warwick Ruth , Fehily Deidre , Watt Suzanne , Gluckman Eliane , Vora Ajay , Contreras Marcela , Navarrete Cristina V. 
Published: December 2004

SummaryCord blood units (n = 5500) stored at the London Cord Blood Bank, including 59 units transplanted into a high risk and heterogeneous group of patients, were analysed. Transplant outcome data was available for 44 patients with a median clinical follow‐up of 14 months (range 3–44 months). Over 40% of the collected units were of ethnic minority origin with a median volume of 79 ml (range 40–240 ml) and a median total nucleated cell (TNC) count of 11·9 × 109/l (range 10·0–24·8 × 109/l). The average patient's weight was 28 kg (range 5–80 kg) and the median age was 8 years (range 0·7–40 years). The median number of nucleated cells infused was 4 × 107/kg (range 1·10–16 × 107/kg). Neutrophil engraftment of 0·5 × 109/l was observed in 33 (74±%) patients with an average time of 28 days (range 11–60). The Kaplan‐Meier estimate of acute graft‐versus‐host disease (grade II >) at day 100 was 37 ± 7% and in 27 (62%) patients, it was grade I or absent. The overall survival and disease‐free survival at 2 years was 49 ± 8% and 41 ± 8%, respectively. Two years after transplantation the survival rate was 69% and 54% for patients receiving a 6/6 or 5/6 HLA matched units, respectively. Infection was the main cause of transplanted related mortality in these patients.
Tumour cell/dendritic cell fusions as a vaccination strategy for multiple myeloma
Authors: Raje Noopur , Hideshima Teru , Davies Faith E. , Chauhan Dharminder , Treon Steven P. , Young Gloria , Tai Yu‐Tzu , Avigan David , Gong Jianlin , Schlossman Robert L. , Richardson Paul , Kufe Donald W. , Anderson Kenneth C. 
Published: December 2004

SummaryMultiple myeloma (MM) cells express certain tumour‐associated antigens (TAAs) that could serve as targets for active‐specific immunotherapy. The aim of the present study was to test the MM/dendritic cell (DC) fusion as a vaccination strategy. We fused MM cells with DC to generate fusion cells (FCs) and tested their antigen presenting cell (APC) function in mixed lymphocyte reactions and cytotoxicity assays. First, the HS Sultan and SK0‐007 HAT sensitive human MM cell lines and DCs generated from peripheral blood of normal donors were fused in the presence of 50% polyethylene glycol to form FCs. Next, tumour cells freshly isolated from patients were similarly fused with autologous DCs to generate FCs. The FCs demonstrated a biphenotypic profile, confirmed both by flow‐cytometry and dual immunofluorescence microscopy. These FCs induced MM‐specific cytotoxicity. FCs, but not MM cells or DCs alone, were potent stimulators of autologous patient T cells. More importantly, FC‐primed autologous peripheral blood mononuclear cells demonstrated major histocompatibility complex‐restricted MM‐specific cytolysis. These studies therefore demonstrated that MM/DC FC can trigger an autologous immune response to MM cells and formed the framework for a clinical trial currently underway.
PRV‐1, erythroid colonies and platelet Mpl are unrelated to thrombosis in essential thrombocythaemia
Authors: Vannucchi Alessandro M. , Grossi Alberto , Pancrazzi Alessandro , Antonioli Elisabetta , Guglielmelli Paola , Balestri Francesca , Biscardi Monica , Bulgarelli Simona , Longo Giovanni , Graziano Claudio , Gugliotta Luigi , Bosi Alberto 
Published: December 2004

SummaryFemales with the monoclonal type of essential thrombocythaemia (ET), based on the X‐chromosome inactivation pattern (XCIP), have previously been shown to present a higher incidence of thrombosis than polyclonal ones. We aimed to assess correlations between XCIP, thrombosis, and three epigenetic markers of ET, namely PRV‐1 overexpression, endogenous erythroid colony (EEC) formation, and reduced platelet Mpl content. Fifty‐three (60%) of 88 subjects studied had monoclonal myelopoiesis and presented a 32% incidence of major thrombosis compared with 6% of polyclonal subjects (P = 0·009). The frequency of abnormalities of PRV‐1, EEC, or Mpl was similar in monoclonal and polyclonal subjects (respectively, 28%, 48%, 75%, and 37%, 27%, 63%), and none of them correlated with thrombosis. We conclude that the exploited epigenetic markers constitute independent phenotypic variations and are not clustered according to monoclonality of myelopoiesis in ET; none of them could serve as a surrogate marker of thrombotic risk in male subjects with ET.
Severe prekallikrein deficiency associated with homozygosity for an Arg94Stop nonsense mutation
Authors: Wynne Jones D. , Russell Geoffrey , Allford Sarah L. , Burdon Kathryn , Hawkins Gregory A. , Bowden Donald W. , Minaee Sophie , Mumford Andrew D. 
Published: December 2004

SummaryAn elderly patient with no abnormal bleeding presented with prolongation of the activated partial thromboplastin time (aPTT). Preincubation of plasma with aPTT reagent caused shortening of the abnormal clotting time. Plasma prekallikrein (PK) activity and antigen were <5 u/dL. Molecular analysis showed a homozygous Arg94Stop substitution in the PK gene, predicted to prevent expression of the mutant allele. The five heterozygous offspring of the proband each showed a normal aPTT but reduced PK activity and antigen. This is the first description of a kindred in which absence of expression of one or both PK alleles has been confirmed by genotype.
Expression of two type 2N von Willebrand disease mutations identified in exon 18 of von Willebrand factor gene
Authors: Hilbert L. , Jorieux S. , Fontenay‐Roupie M. , Guicheteau M. , Fressinaud E. , Meyer D. , Mazurier C. ,   the INSERM Network on Molecular Abnormalities in von Willebrand Disease
Published: December 2004

SummaryType 2N von Willebrand disease (VWD) is characterized by a markedly decreased affinity of von Willebrand factor (VWF) for factor VIII (FVIII). The FVIII binding site has been localized within the first 272 amino acid residues of mature VWF, encoded by exons 18–23. Two substitutions in exon 18 of VWF gene, inducing candidate mutations Y795C and C804F were identified in the heterozygous state in two French patients who also displayed the frequent R854Q mutation in exon 20. Expression studies in Cos‐7 cells showed that these abnormalities, which implicate cysteine residues, induced secretion, multimerization and FVIII binding defects of corresponding recombinant VWF. Results from transfection experiments with R854Q, performed to reproduce the hybrid VWF present in patient plasma, were in agreement with those obtained for patient's plasma VWF. These findings confirm the importance of the VWF D’ domain in FVIII binding. In addition, this work shows that exon 18 should preferentially be sequenced in type 2N VWD patients when the frequent R854Q mutation in exon 20 has been excluded or detected in the heterozygous state.
Dyskinesias and associated psychiatric disorders following streptococcal infections
Authors: Reading Richard 
Published: December 2004

.

Dale RC,
Heyman I,
Surtees RAH,
Church AJ,
Giovannoni G,
Goodman R &
Neville BGR
. (
2004
)

,
89
,
604
–
610
.
Background  The classical extrapyramidal movement disorder following β haemolytic streptococcus (BHS) infection is Sydenham's chorea (SC). Recently, other post‐streptococcal movement disorders have been described, including motor tics and dystonia. Associated emotional and behavioural alteration is characteristic.Aims  To describe experience of post‐streptococcal dyskinesias and associated comorbid psychiatric features presenting to a tertiary referral centre 1999–2002.Methods  In all patients, dyskinetic movement disorders followed BHS pharyngeal infection. BHS infection was defined by pharyngeal culture of the organism, or paired streptococcal serology. Movement disorders were classified according to international criteria, and validated by experienced child neurologists. Psychiatric complications were defined using ICD‐10 criteria using a validated psychiatric interview.Results  In the 40 patients, the following dyskinetic movement disorders were present: chorea (n = 20), motor tics (n = 16), dystonia (n = 5), tremor (n = 3), stereotypies (n = 2), opsoclonus (n = 2) and myoclonus (n = 1). Sixty‐five per cent of  the  chorea  patients  were  female,  whereas  69% of the tic patients were male. ICD‐10 psychiatric diagnoses were made in 62.5%. Using the same psychiatric instrument, only 8.9% of UK children would be expected to have an ICD‐10 psychiatric diagnosis. Emotional disorders occurred in 47.5%, including obsessive‐compulsive disorder (27.5%), generalized anxiety (25%) and depressive episode (17.5%). Additional psychiatric morbidity included conduct disorders (27.5%) and hyperkinetic disorders (15%). Psychiatric, movement and post‐streptococcal autoimmune disorders were commonly observed in family members. At a mean follow‐up of 2.7 years, 72.5% had continuing movement and psychiatric disorders.Conclusion  Post‐streptococcal dyskinesias occur with significant and disabling psychiatric comorbidity and are potential autoimmune models of common ‘idiopathic’ movement and psychiatric disorders in children. Multiple factors may be involved in disease expression including genetic predisposition, developmental status and the patient's sex.