bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expression of fos proto‐oncogene product by monoclonal antibody FO‐120 in smouldering adult T‐cell leukaemia (ATL)
Authors: Iwahashi Masahito , Otsuka Maki , Shimotakahara Shigemi , Uozumi Kimiharu , Hanada Shuichi , Arima Terukatsu , Matsumoto Makoto 
Published: March 2008

We investigated the expression of c‐fos gene product in peripheral blood mononuclear cells of patients with smouldering adult T‐cell leukaemia (ATL) and healthy human T‐lymphotropic virus type‐I (HTLV‐I) carriers by an immunofluorescence assay, using a mouse monoclonal antibody (FO‐120) specific for fos gene product. Peripheral blood mononuclear cells derived from healthy HTLV‐I carriers were rarely positive for FO‐120, less than 2% of the cells weakly reacted with FO‐120, whereas positive cells were detected in more than about 10% of cells from patients with smouldering ATL.FO‐120 appears to be a useful tool for detecting smouldering ATL in asymptomatic HTLV‐I infected people without using molecular techniques.
The very‐long‐term course of polycythaemia: a complement to the previously published data of the Polycythaemia Vera Study Group
Authors: Najean Yves , Dresch Catherine , Rain Jean‐Didier 
Published: March 2008

The very‐long‐term follow‐up of patients initially included in the PVSG protocols provides useful information. The excess risk of cancer after chlorambucil appears to persist for 5 years after stopping this treatment. The risk of leukaemia induced by marrow suppression (32P or chemotherapy) was marked before the 10th year, but low thereafter. Phlebotamy is unacceptable as permanent treatment because of the poor clinical tolerance and the frequency of vascular complications. This treatment is also associated with a risk of early progression towards myelofibrosis with myeloid splenomegaly.In the very long term, 15 years or more after the diagnosis, this complication is the major clinical risk, affecting almost 50% of our patients surviving at this time. The prevention of this type of complication could constitute one of the objectives of future protocols dealing with this disease.
Stereological studies on red corpuscle size produce values different from those obtained using haematocrit‐ and model‐based methods
Authors: Mayhew T. M. , Mwamengele G. L. M. , Self T. J. , Travers J. P. 
Published: March 2008

Summary The routine methods for estimating erythrocyte size (volume and surface area) are not generally unbiased. Using geometric models introduces a bias determined by the ways in which real red blood corpuscles depart in size and shape from the simplistic ideal. Employing haematocrit and red corpuscle count to estimate mean corpuscular volume relies on an implicit assumption that erythrocytes fill three‐dimensional space. However, a biconcave circular disc cannot be space‐filling. The bias is positive and its magnitude depends on erythrocyte geometry and packing density within the centrifuge pellet.We have estimated the volumes, surface areas and shape factors of red blood corpuscles in normal adults (three males, three females) using transmission electron microscopy and stereology. We confirm the lack of sexual dimorphism and find that the mean corpuscular volume is 44 fl (between‐subject coefficient of variation 5%), mean membrane surface area is 87 μm2 (6%) and the shape factor is 18.4 fl fl (11%). The surface is 44% greater than that of a sphere of equal volume. The possible reasons for discrepancies with standard haematological values are discussed. On the basis of observed volumes, we predict that red blood corpuscles account for only 51% of the volume of the red column in standard haematocrit pellets.
Changes in the phenotypic characteristics of eosinophils from patients receiving recombinant human interleukin‐2 (rhIL‐2) therapy
Authors: Rodgers Sheila , Rees Robert C. , Hancock Barry W. 
Published: March 2008

Summary.We have studied the properties of eosinophils from 26 patients with malignant melanoma and 16 patients with renal cell carcinoma (RCC) who were entered into a phase II clinical trial using various schedules of low‐dose rhIL‐2 immunotherapy. Eosinophilia was observed in 65% of melanoma patients and 100% of renal patients when receiving rhIL‐2 therapy.The eosinophil count increased up to 20‐fold approximately 5 d after the appearance of lymphocyte activation markers. This would be consistent with eosinophil kinetics and the release of soluble mediators, for example IL‐5, from lymphocytes. Eosinophils from eosinophilic patients became hypodense compared to their pre‐treatment levels as demonstrated by sedimentation through a discontinuous metrizamide density gradient; they also showed an increased expression of CD4, CD25 and CD11b cell surface activation markers. Eosinophil count could not be correlated to either patient survival or response to therapy in melanoma patients: however, patients with renal cell carcinoma demonstrated a significant correlation (P0·05) between eosinophil count and survival but not with clinical response. Therefore the maximum eosinophil count achieved during rhIL‐2 therapy is of prognostic significance in patients with renal cell carcinoma.
Establishment of a human T‐cell line with deficient surface expression of glycosylphosphatidylinositol (GPI)‐anchored proteins from a patient with paroxysmal nocturnal haemoglobinuria
Authors: Masuda Tetsuya , Yonemura Yuji , Fujimoto Koji , Hidaka Michihiro , Nagakura Shoichi , Nakakuma Hideki , Hata Hiroyuki , Sanada Isao , Kawakita Makoto , Takatsuki Kiyoshi 
Published: March 2008

SummaryA novel interleukin‐2 dependent T‐cell line, PMT‐2Y, was established from the peripheral blood of a patient with paroxysmal nocturnal haemoglobinuria (PNH) by human T lymphotropic virus type I (HTLV‐1)‐mediated transformation. PMT‐2Y cells are positive for CD2, CD3, CD4, CD25, T cell receptor αβ and HLA‐DR, but negative for CD1, CD7, CD8, CD19 and CD20, indicating that the clone belongs to a helper/inducer subset of T cells. PMT‐2Y cells have the monoclonal integration of HTLV‐I proviral DNA, suggesting that they derived from a single clone. Moreover, they lack surface expression of complement regulatory proteins such as DAF (CD55) and CD59, that are the most important glycosylphosphatidylinositol (GPI)‐anchored membrane proteins defective in haemopoietic cells of patients with PNH. Northern blot analysis, however, revealed the production of normal levels of DAF mRNAs. Thus, PMT‐2Y is derived from a PNH T cell clone and may be a useful model to study PNH.
An autoantibody to human plasma prekallikrein blocks activation of the contact system
Authors: Page J. D. , Cadena R. A. DeLa , Humphries J. E. , Colman R. W. 
Published: March 2008

Summary. A patient without a history of bleeding or thromboembolism presented with an activated partial thromboplastin time (aPTT) of 55.1 s (normal 24‐38 s). Incubation of the patient plasma with an equal volume of normal plasma failed to correct the aPTT. suggesting the presence of an inhibitor. The MRVVT (modified Russell Viper venom time) was normal, and the anti‐cardiolipin antibody titres were not elevated, indicating that the presence of a lupus anticoagulant was unlikely. Plasma prekallikrein (PK) measured by a coagulant assay (2 U/dl) was very low, but PK was in the low normal range (65%) when measured by an enzymatic assay (amidolytic) or by an antigenic assay (ELISA). The purified patient IgG reacted with purified PK. the heavy chain, and the 28 kD fragment of the heavy chain, indicating that it contained an autoantibody to PK. The purified IgG did not directly inhibit the amidolytic activity of kallikrein, but it did inhibit the activation of PK to kallikrein by activated factor XII. Activation of the contact system by dextran sulphate, as reflected by the cleavage of HK on a Western blot, was inhibited when the patient IgG was added to pooled normal plasma. The antibody appears to be oligoclonal with IgG1 being most abundant. followed by IgG4. This report appears to be the first of a spontaneously occurring antibody to prekallikrein.
Fine epitope mapping of monoclonal antibodies to the NH2‐terminal part of von Willebrand factor (vWF) by using recombinant and synthetic peptides: interest for the localization of the factor VIII binding domain
Authors: Jorieux Sylvie , Gaucher Christine , Piéatu Geneviégve , Chéarel Ghislaine , Meyer Dominique , Mazurier Claudine 
Published: March 2008

Summary. Two different approaches were used in order to define the epitope of three monoclonal antibodies (MoAbs) against the NH2‐terminal part of the mature subunit of von Willebrand factor (vWF) which contains its factor VIII (FVIII) binding site. First, a vWF cDNA fragment library using the bacteriophage λgt11 expression vector was screened with radiolabelled MoAbs. The epitope of each MoAb was defined, following sequence analysis, by the overlapping DNA sequence of immunoreactive clones. MoAb 32B12, a potent inhibitor of FVIII/vWF interaction, binds within the Glu35‐Ile81 sequence of vWF subunit. MoAb 14A12, a non‐inhibitory antibody, recognizes a sequence within Thr141‐Val220. MoAb 31H3, a partial inhibitory antibody, gives no positive clone. In the second method, a panel of 24 synthetic pentadecapeptides corresponding to the first NH2‐terminal 105 amino acid residues was used to block the binding of inhibitor MoAbs to immobilized vWF in an ELISA system. The localization of MoAb 32B12 epitope was confirmed and restricted to the Met51‐Ala60 sequence, The MoAb 31H3 binding to vWF is inhibited by two synthetic peptides with the overlapping sequence Cys66‐Gly76. All these data confirm that the FVIII binding site of vWF is not limited to the binding area (Thr78‐Thr96) of the previously described MoAbs inhibiting FVIII/vWF interaction but is composed of several key sequences.
Recombinant human erythropoietin for the treatment of the anaemia associated with autologous bone marrow transplantation
Authors: Ayash Lois J. , Elias Anthony , Hunt Myla , Demetri George , Wheeler Catherine , Tepler Isidore , Schwartz Gary , Mazanet Rosemary , Reich Elaine , McCauley Mary , Antman Karen , Anderson Kenneth C. 
Published: March 2008

Summary. Patients with solid tumours undergoing highdose chemotherapy with autologous bone marrow transplantation use an average of 10 units of packed red blood cells (PRBC) while awaiting haemopoietic reconstitution. They are also known to have inappropriately low endogenous erythropoietin levels for their degree of anaemia. This pilot study was designed to determine the effects of recombinant human erythropoietin (rHuEPO) on erythroid recovery and PRBC transfusion requirements.Ten patients received high‐dose chemotherapy (days ‐ 7 to ‐3), bone marrow reinfusion (day 0), and then rHuEPO (day 1 onward). RHuEPO (200 units/kg intravenous bolus daily), along with iron supplementation, was administered for 28 d or until a haematocrit (Hct) of 35% (independent of transfusions) was reached, whichever occurred first. PRBCs were routinely given for Hct 25% and platelets for counts < 20000/μl.Eight (80%) patients developed a brisk reticulocytosis (median peak reticulocyte count 0.32 × 109/l) and a haematocrit 30% independent of red blood cell transfusions within 32 d of receiving marrow, as compared to 20/37 (54%) similarly treated controls. An unexpected finding was the more rapid engraftment in myeloid and platelet lineages in a subset of rHuEPO‐treated patients. Quick return of red blood cells (17 v 33d) (P = 0.0001), platelets (14 v 19d) (P = 0.04), and neutrophils (13 v 25d) (P = 0.01) (with circulating myeloblasts and early myeloid forms) characterized recovery from an ifosfamide‐based intensification with rHuEPO support. Similar trilineage enhancement of haemopoiesis did not occur with the possibly more myeloablative cyclophosphamide‐based regimens. Despite the enhancement by rHuEPO on reticulocytosis, there was no significant decrease in PRBC transfusion requirements.RHuEPO proved to be a well‐tolerated agent in enhancing reticulocytosis following high‐dose chemotherapy. further study to elucidate the activity of erythropoietin on both erythroid and non‐erythroid growth and maturation appears warranted.
Peripheral mononuclear cells of haemophiliacs with chronic liver disease are infected with replicating hepatitis C virus
Authors: Henin Christine , Makris Mike , Brown Julie , Peake Ian R. , Preston Eric F. 
Published: March 2008

SummaryMost haemophiliacs treated with non‐virally inactivated concentrates have been infected with the hepatitis C virus (HCV). 19/21 (90%) patients with HCV antibody were found to have HCV RNA in their serum and in 16 of these it was also detected in peripheral blood mononuclear cells (PBMC). We used specific primers to detect the negative (replicative) strand of this single positively stranded virus. The negative strand was detected in the serum or PBMC of 16 patients indicating active replication outside the liver. The detection of replicating HCV RNA in the cells of HIV negative haemophiliacs could explain at least some of the immunological abnormalities previously reported in these patients and attributed to clotting factor concentrates.
Possible role of granulocyte‐macrophage colony stimulating factor (GM‐CSF) on the rapid progression of AIDS‐related Kaposi's sarcoma lesions in vivo
Authors: Hermans Philippe , Gori Andrea , Lemone Marc , Franchioly Patricia , Clumeck Nathan 
Published: March 2008

SUMMARY. Drug‐related neutropenia is a common observation in AIDS patients. Haematological growth factors are therefore increasingly used in combination with myelotoxic agents to reduce the risk of infection and to improve the haematological tolerance of these regimens.We report a case of an AIDS patient with Kaposi's sarcoma who received GM‐CSF for severe neutropenia due to antitumour chemotherapy combining α‐interferon 2b and zidovudine. During GM‐CSF administration there was a marked increase in the size of the Kaposi's sarcoma lesions as confirmed by ultrasonographic examination. As GM‐CSF in vitro has been shown to promote Kaposi's sarcoma‐like cell cultures, we discuss the potential role of this growth factor in increasing Kaposi's sarcoma lesions in vivo.
All‐trans retinoic acid promotes a differential regulation of adhesion molecules on acute myeloid leukaemia blast cells
Authors: Noto R. Di , Schiavone E. M. , Ferrara F. , Manzo C. , Pardo C. Lo , Vecchio L. Del 
Published: March 2008

Summary. In the present study we investigated the membrance expression of selectin ligands (CD15/Lex, CDw65/VIM2, CD15s/sLex), β2 integrins (CD11a/LFA‐1, CD11b/Mac‐1) and CD45 phosphatase isoforms (CD45RA, CD45RO on leukaemic cells from 28 patients with acute myeloid malignancies cultured with and without all‐trans retinioc acid (ATRA). Within each adhesion system, ATRA was bale to differentially regulate distinct molecules. Furthermore, it was able to exert effects specific for acute promyelocytic leukaemia (APL) blast cells, as well as to induce a series of non‐cytotype‐restricted phenotypic changes. An impressive feature of ATRA induction was a simultaneous increase in the expression of CD15, CDw65 and CD11b on leukaemic promyelocytes. The sialylated antigen CD15s, however, Showed results independent from the other two carbohydrates (CD15 and CDw65), suggesting a differential enzymatic regulation within the selectin ligands system.In spite of the well‐recognized expression of CD11a throughout all stages of normal myeloid differentiation, APL blast cells were found to virtually lack LFA‐1 expression. Moreover, ATRA was unable to promote and up‐regulation of this antigen in APL, while inducing a frequent down‐modulation in non‐APL cases constitutively expressing this antigen. In APL cases ATRA generated an asynchronous phenotype (CD15+, CDw65+, CD11b+, CD11a‐), undetectable on normally maturing myeloid cells, but consistent with the concept that incomplete differentation, in terms of surface molecule expression, can be sufficient to obtain therapeutic results.
Recombinant human immunodeficiency virus type‐1 (HIV‐1) Tat protein sequentially up‐regulates IL‐6 and TFG‐β1 mRNA expression and protein synthesis in peripheral blood monocytes
Authors: Gibellini Davide , Zauli Giorgio , Re Maria Carla , Milani Daniela , Furlini Giuliano , Caramelli Elisabetta , Capitani Silvano , Placa Michele La 
Published: March 2008

Summary. In this study we evaluated the effect of human immunodeficiency virus type 1 (HIV‐1) recombinant Tat protein on mRNA expression and protein synthesis of two inflammatory cytokines ‐ interleukin‐6 (IL‐6) and transforming growth factor‐β1 (TGF‐β1) ‐ by peripheral blood (PB) monocytes. Whereas maximal levels of IL‐6 protein were recovered in PB monocyte culture supernatants after 24–48 h from the addition of 1 μg/ml of recombinant Tat, TGF‐β1 showed a slower and progressive increase, reaching maximal levels only after 72–96h of culture. Consistently, the analysis of the steady‐state levels of mRNA showed a sharp increse of IL‐6 mRNA expression after 24h of culture, with a slow decline thereafter. On the other hand, TGF‐β1 mRNA expression showed a slow increase only after 72–96h of culture. Moreover, IL‐6 appeared involved in the up‐regulation of TGF‐β1, because the addition of a neutralizing anti‐IL‐6 antibody to Tat‐treated PB monocyte cultures significantly reduced the amounts of TGF‐β1 recovered in the culture supernatants after 96 h.The present demonstration that HIV‐1 Tat protein directly up‐regulates IL‐6 expression and stimulates TGF‐β production both directly and indirectly, through early IL‐6 production, could have important implications in the pathogenesis of HIV‐1 disease.
Homozygous β‐thalassaemia resulting in the β‐thalassaemia carrier state phenotype
Authors: Rosatelli Maria Cristina , Pischedda Alessandra , Meloni Alessandra , Saba Luisella , Pomo Anna , Travi Maurizio , Fattore Silvia , Cao Antonio 
Published: March 2008

Summary. This paper describes the phenotypic manifestations of a very mild β‐thalassaemia mutation detected in several members of two families of Italian descent. The molecular defect, defined by denaturing gradient gel electrophoresis analysis and direct sequencing. consists of a C G substitution at position 844 of IVSII of the β‐globin gene within the consensus sequence of IVSII acceptor splice site. Heterozygotes for this mutation show a haematological phenotype ranging in severity from silent β‐thalassaemia to that of a mild β‐thalassaemia carrier silent β‐thalassaemia to that of a mild β‐thalassaemia carrier state, whereas homozygotes have the typical manifestations commonly resulting from heterozygosity for a β‐thalassaemia mutation. Compound heterozygotes for the IVSII nt844 (C G) mutation and a severe β‐thalassaemia mutation have the phenotype of thalassaemia intermedia.This paper indicates that the presence of borderline red blood cell indices or HbA2 values should make one suspect the presence of a very mild or silent β‐thalassaemia.
Expression and functional role of c‐kit ligand (SCF) in human multiple myeloma cells
Authors: Lemoli Roberto M. , Fortuna Alessandra , Grande Alexis , Gamberi Barbara , Bonsi Laura , Fogli Miriam , Amabile Marilina , Cavo Michele , Ferrari Sergio , Tura Sante 
Published: March 2008

Summary. In this study we investigated the proliferation of three well‐documented MM lines and 10 bone marrow samples from myeloma patients in response to rh‐SCF alone and combined with Interleukin‐6 (IL‐6), IL‐3 and IL‐3/GMCSF fusion protein PIXY 321. Neoplastic plasma cells were highly purified (>90%) by immunomagnetic depletion of T, myeloid. monocytoid and NK cells. The number of S‐phase cells was evaluated after 3 and 7d of liquid culture by the bromodeoxyuridine (BRDU) incorporation assay. The proliferation of RPMI 8226 and U266 cell lines was also assessed by a clonogenic assay. All the experiments were performed in serum‐free conditions. RPMI 8226 cell line was not stimulated by SCF which also did not augment the proliferative activity of IL‐6, IL‐3 and PIXY‐321. Conversely, SCF addition resulted in 2.4‐fold increase of the number of U266 colonies and in a higher number of U266 and MT3 cells in S‐phase (24.5 ± 2% SEM v 14.5 ± 1% SEM and 32 ± 3% SEM v 21 ± 4% SEM, respectively; P < 0.05). The c‐kit ligand also enhanced the proliferation of MT3 and U266 cells mediated by the other cytokines. Anti‐SCF polyclonal antibodies completely abrogated the proliferative response of MT3 cells to exogenous SCF and markedly reduced the spontaneous growth of the same cell line. Reverse transcriptase‐polymerase chain reaction amplification (RT‐PCR) did detect SCF mRNA in MT3 and RPMI 8226 cells. Moreover, secreted SCF was found, in a biologically active form, in the supernatant of the two cell lines by the M07e proliferation assay.When tested on fresh myeloma samples, SCF increased the number of S‐phase plasma cells (4.7 ± 1.6% v 3.4 ± 1.3% in control cultures: P= 0.02). Significant proliferation was also induced by IL‐6 (7 ± 2.3% of BRDU+ cells: P = 0.006), IL‐3 (5.3 ± 1.3%; P=0.01) and PIXY‐321 (5.4 ± 1.6%; P = 0.02). The addition of SCF significantly enhanced the proliferation of myeloma cells responsive to IL‐6. In summary, our results indicate that SCF is expressed in MM cells and stimulates the proliferation of neoplastic plasma cells.
Peripheral blood stem cells (PBSCs) collected after recombinant granulocyte colony stimulating factor (rhG‐CSF): an analysis of factors correlating with the tempo of engraftment after transplantation
Authors: Bensinger W. I. , Longin K. , Appelbaum F. , Rowley S. , Weaver C. , Lilleby K. , Gooley T. , Lynch M. , Higano T. , Klarnet J. , Chauncey T. , Storb R. , Buckner C. D. 
Published: March 2008

SummaryFactors affecting mobilization and engraftment were analysed in 54 patients undergoing transplant using autologous PBSCs mobilized with high‐dose recombinant granulocyte stimulating factor (rhG‐CSF). Patients received 5‐7 d of rhG‐CSF. 16 μg/kg/d, administered subcutaneously. PBSCs were harvested by leukapheresis using automated continuous‐flow blood cell separators beginning on day 4 of rhG‐CSF, processing 10 litres of whole blood, for 2‐6 consecutive days. Transplants were performed for the following diseases: breast cancer (n = 22), non‐Hodgkin's lymphoma (n = 18), multiple myeloma (n = 7) and other (n = 7). Engraftment was rapid with patients reaching a neutrophil count of 1 × 109/1a median of 12 d (range 9‐22) after transplant. Platelets > 20 × 109/1 independent of transfusion support were achieved a median of day 10 (range 7‐60) after infusion. Multiple factors potentially influencing engraftment were examined using a Cox regression model. The number of CD34+ cells per kg was highly correlated with the time to achievement of granulocyte and platelet recovery (P < 0.012, 0.0001). The use of a post‐infusion growth factor and a radiation preparative regimen was important for neutrophil recovery, and a diagnosis of breast cancer was important for platelet recovery. In an analysis by linear regression of the logarithm of CD34+ cells collected, lower age, marrow without disease, no prior radiation, and lower number of prior chemotherapy regimens, were important factors influencing larger numbers of CD34+ cells in collections.