bluuebunny/crossref_metadata_2025_split huggingface dataset:
Absence of IL‐6 receptor expression in fresh childhood Burkitt's lymphoma cells and induction of IL‐6 receptors by Epstein‐Barr virus in vitro
Authors: Tomeczkowski Jörg , Zur Stadt Udo , Reiter Alfred , Welte Karl , Sykora Karl‐Walter 
Published: November 2003

Interleukin‐6 (IL‐6) is a cytokine which is necessary for the differentiation of activated B cells and growth of early haemopoietic progenitors. It is used for ex‐vivo expansion of myeloid progenitors in the setting of high‐dose chemotherapy with autologous bone marrow transplantation (BMT). Expression of the IL‐6 receptor (IL‐6R) was examined in six fresh Burkitt’s lymphoma (BL) cell preparations and 12 BL cell lines by reverse transcriptase polymerase chain reaction (RT‐PCR) and flow cytometry (FCM). Inducibility of IL‐6R mRNA expression by Epstein‐Barr virus (EBV) was studied by comparing two uninfected cell lines with the same cell lines infected by EBV. The phenotype of the BL cells lines was analysed by FCM and by proliferation assays in the presence of anti‐IgM antibodies.None of the fresh BL cells expressed the IL‐6 receptor. The BL cell lines expressed varying degrees of IL‐6R mRNA and protein. In vitro infection of EBV‐negative BL cell lines resulted in up‐regulation of IL‐6R mRNA. There was no proliferative response of the BL cell lines to IL‐6, including the cells that expressed the receptor. Compared to uninfected BL cell lines, EBV‐infected cell lines and lymphoblastoid cell lines (LCLs) showed a weaker or no response to anti‐IgM antibodies, indicating a more mature phenotype of these cells. We conclude that the IL‐6 receptor is not expressed in fresh childhood BLs, but only in BL cell lines. EBV infection in vitro leads to an up‐regulation of IL‐6R mRNA but not to increased proliferation. This makes growth stimulation of contaminating BL cells in the setting of autologous BMT unlikely.
The effect of cardiopulmonary bypass on circulating megakaryocytes
Authors: Wilde N. T. , Burgess R. , Keenan D. J. M. , Lucas G. S. 
Published: November 2003

Megakaryocytes (Mks) are found in the lungs and the blood stream as well as in the bone marrow. We modified a whole blood filtration method for Mks by immunostaining for CD61 using biotin streptavidin, and used this technique to study Mks and their morphology in the central venous and arterial circulations before, during and after cardiopulmonary bypass (CPB) in haematologically normal patients undergoing routine cardiac surgery.Blood samples were taken immediately after the insertion of central venous (V) and arterial (A) catheters and after thoracotomy, immediately before bypass. Further samples were taken after 60–90 min on‐CPB and 180–240 min post‐bypass. In comparison with the steady state before bypass, circulating Mk levels in blood on bypass increased dramatically, from (V) 10.93 ± 3.94/ml (mean ± SD) to 36.48 ± 11.52/ml and from (A) 8.37 ± 4.39/ml to 38.65 ± 20.68/ml. This effect was still present, to a lesser extent, 180–240 min post‐bypass. Circulating levels of Mks were consistently lower in the arterial circulation than in the venous circulation off bypass, but levels in the two circulations were comparable during CPB, confirming previous suggestions that the lungs are net removers of Mks from the circulation. Type 4 Mks, the largest and most normal morphologically, were rarely seen in arterial blood, but increased significantly during CPB, indicating that the lungs selectively remove large Mks.The lungs appear to play an active role in the regulation of Mk levels. This is lost during CPB and despite the extracorporeal 40 μm arterial line filter, large Mks enter the systemic circulation. More effective extracorporeal filtration of large Mks might reduce the neurological impairment seen in some patients who have undergone CPB.
Rarity of microsatellite genomic instability in B‐cell non‐Hodgkin's lymphomas in hepatitis C virus‐infected patients
Authors: De Vita Salvatore , Gasparotto Daniela , Pivetta Barbara , Vukosavljevic Tamara , Zagonel Vittorina , Carbone Antonino , Boiocchi Mauro 
Published: November 2003

Several groups have emphasized the likely impli‐cation of the hepatitis C virus (HCV) in a fraction of B‐cell non‐Hodgkin's lymphomas. Since only a minority of patients with HCV infection and monoclonal mixed cryoglobulinaemia develop overt lymphoma, the identification of predisposing factors has relevant clinical implications. The replication error phenotype (RER+), as revealed by widespread microsatellite instability, is caused by defects in DNA mismatch repair genes, and has been frequently disclosed in subsets of B‐cell lymphomas with underlying infection and chronic inflammation. We therefore investigated the occurrence of the RER+ phenotype in a series of eight consecutive B‐cell NHLs in patients with chronic infection by HCV. A polymerase chain reaction‐based assay was used to analyse an extended panel of 15 microsatellite loci.Microsatellite instability was not observed in six tumour samples in any locus; the two remaining cases showed instability at only one locus.Therefore genetic instability by defects in DNA mis‐match repair genes should not represent the general mechanism predisposing to overt lymphoma in HCV‐infected patients. Although a clearer definition of HCV‐related B‐cell disorders should better address future studies on genetic instability in larger series, we recommend additional oncogenetic pathways as the target of further research.
Effects of in vivo administration of G‐CSF on neutrophil and eosinophil adhesion
Authors: Håkansson L. , Höglund M. , Jönsson U.‐B. , Torsteinsdottir I. , Xu X. , Venge P. 
Published: November 2003

The effect in vivo of G‐CSF on neutrophil and eosinophil adhesion was studied after subcutaneous administration to six healthy individuals of human recombinant glycosylated G‐CSF (lenograstim) (3 μg/kg) for 6 consecutive days.Basal adhesion and adhesion to E‐selectin, VCAM‐1 and ICAM‐1 of neutrophil and eosinophil granulocytes were measured selectively. During G‐CSF administration neutrophil basal adhesion increased from 7.4 ± 3.9% (mean ± SD) to 55.8 ± 12.9% and 23.2 ± 4.4%, 4 and 7 d, respectively, after start of the administration. At the same time points eosinophil basal adhesion increased from 7.1 ± 2.4% to 37.7 ± 6.1% and 13.1 ± 5.3%, respectively. When adhesion was measured in the presence of Mn2+, which increases the functional activity of integrins, an even higher increase of neutrophil and eosinophil basal adhesion was noted 4 and 7 d, respectively, after start of G‐CSF administration. In parallel with the enhanced basal adhesion neutrophil adhesion to E‐selectin and ICAM‐1 and eosinophil adhesion to E‐selectin, VCAM‐1 and ICAM‐1 were significantly (P < 0.05) increased after 4 d of G‐CSF administration as was neutrophil cell surface expression of CD11b and CD18. In vitro G‐CSF induced minimal changes of granulocyte basal adhesion and inhibition of the adhesion to E‐selectin. 10 ng/ml TNFα significantly increased neutrophil and eosinophil basal adhesion and adhesion to VCAM‐1 and ICAM‐1.In summary, administration of G‐CSF to healthy subjects induced enhanced adhesion of neutrophil and eosinophil granulocytes, probably mediated by an increase of the functional capacity of β1‐ and β2‐integrins. The induction of increased levels of TNFα might be one mechanism behind the in vivo effect of G‐CSF administration.
Elevated levels of basic fibroblast growth factor in megakaryocytes and platelets from patients with idiopathic myelofibrosis
Authors: MARTYRÉ M.‐C. , LE BOUSSE‐KERDILES M.‐C. , ROMQUIN N. , CHEVILLARD S. , PRALORAN V. , DEMORY J.‐L. , DUPRIEZ B. 
Published: November 2003

Idiopathic myelofibrosis, or agnogenic myeloid metaplasia, is a chronic myeloproliferative disorder characterized by clonal expansion and marrow fibrosis. Although marrow fibrosis appears to be a reactive process, it substantially contributes to impaired haemopoiesis. During the last few years the implication of megakaryocyte‐derived growth factors in its pathogenesis has been documented.We previously reported increased expression of TGF‐β in patients with idiopathic myelofibrosis. In the present study we show that circulating megakaryocytic cells from such patients expressed high levels of basic fibroblast growth factor (bFGF). An increased expression of bFGF was also detected in patients’ platelets. Under culture conditions, bFGF present in megakaryocytic cells was not exported into the medium, consistent with the fact that bFGF is devoid of a secretion peptide signal. Interestingly, this lack of bFGF secretion was observed in all patients but one, who was in an accelerated phase of the disease and presented an important percentage of circulating megakaryoblasts.
AMYLOIDOSIS: A REVIEW OF RECENT DIAGNOSTIC AND THERAPEUTIC DEVELOPMENTS
Authors: Gillmore Julian D. , Hawkins Philip N. , Pepys Mark B. 
Published: November 2003

Amyloid deposition is associated with a diverse range of disorders that includes Alzheimer's disease, type II diabetes mellitus and dialysis arthropathy. Although less common, systemic AA and AL amyloidosis remain important because effective treatments have increasingly become available.The pathology in all forms of amyloidosis involves the extracellular deposition of protein as characteristic fibrillar aggregates which interfere with tissue structure and function. Amyloid fibrils are derived from different unrelated proteins in the different forms of the disease but share many common properties, including the capacity to bind the normal plasma protein serum amyloid P component (SAP). This is the basis for our development of radiolabelled SAP as a nuclear medicine tracer for the diagnosis and quantitative monitoring of amyloid. Serial studies have shown that the deposits are far from inert but are actually turned over quite rapidly in many patients.The treatment of amyloidosis involves supportive measures whilst every effort is made to reduce the supply of the respective fibril precursor protein. Under favourable circumstances further amyloid deposition will be prevented, existing deposits will regress and improvement of organ function will occur. Since this strategy is not always possible or may fail, new approaches to inhibit fibril formation and promote regression of amyloid are being pursued.
Outcome and lineage involvement in t(12;21) childhood acute lymphoblastic leukaemia
Authors: Lanza Carlo , Volpe Gisella , Basso Giuseppe , Gottardi Enrico , Barisone Elena , Spinelli Monica , Ricotti Emanuela , Cilli Vania , Perfetto Fatima , Madon Enrico , Saglio Giuseppe 
Published: November 2003

The t(12;21)(p13;q22) translocation has been described recently as the most recurrent genetic lesion in paediatric acute lymphoblastic leukaemias (ALLs). It has also been associated with B‐precursor lineage involvement and good outcome.We tested 51 diagnostic paediatric ALLs and found 11 cases with molecular evidence of the t(12;21). Interestingly, amongst t(12;21) positive patients, we report three cases with hybrid phenotype, and two cases showing an aggressive and fatal disease. Our data show that the t(12;21) does not represent an independent good‐risk indicator. Long follow‐ups and additional molecular investigations are needed to assess the prognostic and pathogenetic relevance of t(12;21) in childhood ALLs.
The increase of plasminogen activator inhibitor activity is associated with graft occlusion in patients undergoing aorto‐coronary bypass surgery
Authors: Rifón J. , Páramo J. A. , Panizo C. , Montes R. , Rocha E. 
Published: November 2003

Early graft occlusion is a common complication in patients undergoing aorto‐coronary bypass surgery. Both mechanical and haemostatic factors play a role in the pathogenesis of thrombotic occlusion. Several studies have demonstrated a relationship between fibrinolytic activity and venous or arterial thrombosis. We undertook this study to evaluate the possible contribution of the fibrinolytic system to postoperative occlusion in patients undergoing aorto‐coronary bypass graft (CABG).A venous occlusion (VO) test was performed preoperatively in 82 patients undergoing revascularization procedures. Before and after VO the euglobulin fibrinolytic activity and tissue type plasminogen activator (t‐PA) activity and antigen were measured. Plasminogen activator inhibitor (PAI) activity and antigen and fibrinogen were also assessed in the preocclusion sample. An angiography performed 10 d postoperatively showed graft occlusion in 23% of patients. Patients with graft occlusion had significantly higher preoperative PAI activity than patients without occlusion (P < 0.001). Reduced fibrinolytic response and t‐PA capacity was also observed in the group of patients with graft occlusion (P < 0.03 and P < 0.02 respectively).We found a reduced preoperative fibrinolytic response, mainly related to high plasma PAI activity in patients with postoperative graft occlusion. These results suggest that increased PAI activity might have a predictive value for early thrombosis in patients undergoing CABG.
Clinical relevance of T‐cell receptor delta gene rearrangements in childhood B‐precursor cell acute lymphoblastic leukaemia
Authors: DÍaz M. A. , Garcia‐Sanchez F. , Vicario J. L. , Ramirez M. , Balas A. , Madero L. 
Published: November 2003

The large majority of childhood B‐precursor cell acute lymphoblastic leukaemia cases present IgH and TCRδ gene rearrangements. These rearrangements have been widely used as specific markers for monitoring minimal residual disease. However, their prognostic value still remains unclear. In order to determine whether IgH and TCRδ gene rearrangements have any influence on relapse and event‐free survival (EFS), we analysed the clinical impact of these genetic characteristics in 51 B‐precursor acute lymphoblastic leukaemia patients. 46/51 patients (90.2%) showed IgH gene rearrangements by Southern blot and/or polymerase chain reaction (PCR) analysis. No statistically significant associations were found between IgH gene rearrangement pattern and age, sex, WBC count, immunophenotype, risk factor, relapse or EFS. 27/41 patients (66%) showed Vδ2Dδ3 recombination by Southern blot and/or PCR analysis. At a median follow‐up of 53 months the estimated 5‐year EFS probability was 78 ± 3% for the whole group. The EFS probability among patients with a Vδ2Dδ3 recombination pattern in the TCRδ locus was 90 ± 3%, whereas for patients without Vδ2Dδ3 recombination was 39 ± 13% (P < 0.005).IgH rearrangement patterns do not appear to influence relapse or EFS probability. However, TCRδ gene rearrangement patterns have a relevant impact on the relapse rate and the EFS probability. Patients with Vδ2Dδ3 recombination have better clinical outcome than patients without this recombination, independent of any other prognostic factors.
A phenylalanine‐55 to serine amino‐acid substitution in the human glycoprotein IX leucine‐rich repeat is associated with Bernard‐Soulier syndrome
Authors: NORIS Patrizia , SIMSEK Suat , STIBBE Jean , Kr. VON DEM BORNE Albert E. G. 
Published: November 2003

The platelet membrane glycoprotein (GP) Ib–IX–V complex, the major von Willebrand factor receptor on platelets, is absent or dysfunctional in patients with the Bernard‐Soulier syndrome (BSS). The four single subunits of the GPIb–IX–V complex (GPIbα, Ibβ, IX and V) are molecular products of different genes. Several point mutations and deletions affecting the GPIbα gene have been identified as the cause of BSS, whilst in four BSS families a GPIX gene defect has been reported. Moreover, a single case of BSS has been associated with a genetic defect of GPIbβ. We investigated the molecular basis of another case of BSS with a deficient expression of GPIX, as detected by immunofluorescence studies. After amplification of the entire GPIX coding region, nucleotide sequence analysis showed a homozygous single point mutation predicting a phenylalanine to serine substitution at position 55 of the mature GPIX within its unique leucine‐rich repeat. By allele‐specific oligonucleotide hybridization we confirmed the homozygosity of the patient as well as the carrier state of two out of three of his children studied. Although the parents of the patient, who were first cousins, were no longer alive and thus not available for study, we speculate that the molecular defect observed in the proband was inherited from both parents, who probably were heterozygous for this GPIX gene defect.This study confirms that BSS may be caused by many different subtle molecular defects that often prevent the assembly and expression of a functional GPIb–IX–V complex.
Generation of multinuclear tartrate‐resistant acid phosphatase positive osteoclasts in liquid culture of purified human peripheral blood CD34+ progenitors
Authors: Pierelli Luca , Scambia Giovanni , D'Onofrio Giuseppe , Ciarli Marina , Fattorossi Andrea , Bonanno Giuseppina , Menichella Giacomo , Battaglia Alessandra , Benedetti Panici Pierluigi , Tommasi Maria , Mancuso Salvatore , Leone Giuseppe 
Published: November 2003

Circulating CD34+ cells were isolated from leukapheresis products collected from patients with ovarian cancer. CD34− contaminating cells, identified immediately after immunoselection, ranged from 5% to 25% in five different experiments and were predominantly CD3+ T‐lymphocytes (range 2–12%), CD3−/CD16+/CD56+ natural killer cells (range 2–11%) and rare mature CD15+/CD11b+ granulocytes (range 1–2%). CD34+ cells were cultured in liquid medium in the presence of interleukin‐3, granulocyte‐macrophage colony stimulating factor, stem cell factor, granulocyte colony stimulating factor and a powerful proliferation with prevalent differentiation along the granulocytic/monocytic lineage was obtained. After 10 d of culture a small but consistent number of early multinucleated osteoclasts were identified with a frequency of one cell per 700 granulocytic/monocytic cells, as revealed by cytologic examination. This observation was confirmed by staining for tartrate‐resistant acid phosphatase activity which revealed red multinucleated elements with a frequency comparable to that reported above. Conversely, no osteoclasts were observed in those cultures in which macrophage overgrowth was obtained by culturing CD34+ cells until day 35.These observations suggest that circulating progenitors have a multilineage potential in vitro and contribute to the clarification of osteoclast development in humans; additionally, they provide the basis for the future development of optimized osteoclast culture techniques in liquid medium and the basic culture system, to test the distinct activity of 1,25(OH)2D3, parathyroid hormone, interleukin‐11 and of other cytokines on osteoclast development in humans.
Measurement of endogenous plasma thrombopoietin in patients with acquired aplastic anaemia by a sensitive enzyme‐linked immunosorbent assay
Authors: Kojima Seiji , Matsuyama Takaharu , Kodera Yoshihisa , Tahara Tomoyuki , Kato Takashi 
Published: November 2003

We measured the endogenous plasma concentration of thrombopoietin (TPO) in 76 patients with acquired aplastic anaemia (AA) by a sensitive sandwich enzyme‐linked immunosorbent assay (ELISA). The plasma TPO concentrations were significantly higher in AA patients when compared to healthy control subjects (P < 0.0001) and there was a significant negative correlation between plasma TPO concentrations and platelet counts in 54 AA patients who had not received any platelet transfusions prior to sampling. On the other hand, there was no statistically significant correlation between the TPO concentrations and platelet counts in 22 AA patients who had previously received platelet transfusions.We studied serial changes of plasma TPO concentration in 24 patients who showed an increase in their platelet counts following bone marrow transplantation or immunosuppressive (IS) therapy. Although a decrease in plasma TPO concentration was observed, levels remained above the range of normal healthy controls even in the patients who attained normal platelet counts following therapy. A decrease in TPO concentrations was observed in only half of the responders to IS therapy. Whether exogenous TPO will result in increased platelet counts in AA patients with high TPO levels remains to be determined.
Protection by α2‐macroglobulin of tissue plasminogen activator against inhibition by plasminogen activator inhibitor‐1
Authors: IEKO M. , SAWADA K. , YASUKOUCHI T. , SAKURAMA S. , TOHMA Y. , SHIROSHITA K. , KUROSAWA S. , OHMOTO A. , KOHNO M. , SATOH M. , KOIKE T. 
Published: November 2003

Tissue plasminogen activator (tPA) is widely used in the treatment of acute myocardial infarction (MI). However, its thrombolytic efficacy does not correlate with the dose administered. The interactions between tPA, α2‐macroglobulin (α2‐M), and plasminogen activator inhibitor‐1 (PAI‐1) were investigated both in vitro and in patients undergoing tPA therapy for MI in an attempt to identify variables that might affect the clinical efficacy of tPA.Purified α2‐M (5.4 mg/ml) protected 16.0% or 22.4% of tPA (12.5 IU/ml) activity from inhibition by PAI‐1 at 4 or 8 IU/ml in vitro. Of nine patients treated with 5–20 mega IU of tPA for MI, the plasma activity of tPA remained increased for 15–30 min after the cessation of infusion in eight; the patient who failed to exhibit a persistent increase in tPA activity had a low plasma concentration of α2‐M. Total tPA activity, derived from the area under the activity‐versus‐time curve (AUC), showed a significant inverse correlation with the ratio of the plasma PAI‐1 activity to the plasma α2‐M concentration. Total tPA activity did not correlate with plasma PAI‐1 activity or plasma α2‐M concentration alone. Results suggest that α2‐M, by binding to tPA, protects the latter against inhibition by PAI‐1.
Clinical characteristics predict response to antithymocyte globulin in paroxysmal nocturnal haemoglobinuria
Authors: Paquette Ronald L. , Yoshimura Ryan , Veiseh Charles , Kunkel Lori , Gajewski James , Rosen Peter J. 
Published: November 2003

Seven patients with paroxysmal nocturnal haemoglobinuria (PNH) were treated with antithymocyte globulin (ATG). Each patient received ATG (20 mg/kg/d) for 8 d and prednisone to prevent or control serum sickness. Three patients experienced a sustained improvement in at least one peripheral blood cytopenia, including one patient who had a complete trilineage response. Several pre‐treatment clinical features appeared to be associated with response to ATG. All responding patients had hypoproliferative features including depressed platelet counts (<30×109/l), and a minor degree of chronic haemolysis as indicated by relatively low reticulocyte counts (<100×109/l), lactate dehydrogenase (<1000 U/l) and total bilirubin (<17μmol/l) levels. Responding patients continued to have chronic low‐grade haemolysis after their response to immunosuppression that was similar to that observed prior to treatment. The non‐responding patients had a classic haemolytic form of PNH characterized by elevated reticulocyte counts (>100×109/l), lactate dehydrogenase (>2000 U/l) and total bilirubin (>17μmol/l) levels.The impaired haemopoiesis that occurs in hypoproliferative PNH may respond to ATG treatment, but the haemolytic component of the disease, and hence the PNH clone, is not altered by immunosuppressive therapy.