bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dose of desferrioxamine and evolution of HIV‐1 infection in thalassaemic patients
Authors: Costagliola Dominique G. , Montalembert Mariane de , Lefrère Jean‐Jacques , Briand Catherine , Rebulla Paolo , Baruchel Sylvain , Dessi Carlo , Fondu Pierre , Karagiorga Markissia , Perrimond Henri , Girot Robert 
Published: March 2008

SummaryTo study the relationship between the dose of desferrioxamine (DFX) and the progression of the HIV‐1 disease in thalassaemia major patients (TMP), 64 seropositive TMP patients were studied. Cumulative incidence of CDC stage IV was calculated using a non‐parametric life‐table method. The association with the mean daily dose of DFX was tested with a Cox proportional hazards model which was also used to adjust for confounding variables. The median of the mean daily dose of DFX over the seropositive period was 40mg/kg (range 0‐65mg/kg). Age at seroconversion (P < 0.02) and splenectomy (P < 0.03) were found to be associated with the mean daily dose of DFX. 6.5 years after seroconversion, 11% of those who had been prescribed more than 40mg/kg of DFX daily had entered stage IV versus 35% of those who had been prescribed a lower dose (P < 0.01). When the dose was taken as a continuous variable it was found that the rate of progression was significantly smaller in TMP receiving a higher dose (P < 0.002). even after adjusting for age and splenectomy (P < 0.02). Although it should be noted that these results were obtained in an observational study, possibly biased by a non‐random allocation of the DFX dose, we believe that they are striking enough to support the claim that the role of DFX in the progression of HIV disease should be further evaluated.
Restoration of normal polyclonal haemopoiesis in patients with chronic myeloid leukaemia autografted with Ph‐negative peripheral stem cells
Authors: Bergamashi Gaetano , Podesta Marina , Frassoni Francesco , Rosti Vittorio , Carella Angelo Michele , Saglio Giuseppe , Cazzola Mario 
Published: March 2008

SummaryOnly a minority of patients with chronic myeloid leukaemia (CML) benefit from allogeneic bone marrow transplantation (BMT), a potentially curative therapy, or from treatment with interferon alpha, which prolongs survival in cytogenetic responders. In Genoa a programme has been initiated in which CML patients are autografted with Ph‐negative peripheral stem cells. To assess the pattern of marrow reconstitution, we studied the clonality of haemopoiesis in five females who engrafted and were Philadelphia chromosome negative. This was performed by evaluating the methylation patterns of the X‐linked hypervariable DXS255 locus with the probe M27β. All four analysable women showed polyclonal methylation patterns in both granulocytes and T lymphocytes, suggesting that marrow reconstitution occurred from normal residual stem cells.
Generation of anti‐tumour activity by OKT3‐stimulation in multiple myeloma: in vitro inhibition of autologous haemopoiesis
Authors: Attisano Carmela , Bianchi Alberto , Montacchini Laura , Carlesso Nadia , Peola Silvia , Bruno Benedetto , Roux Viviana , Ferrero Dario , Gallo Eugenio , Boccadoro Mario , Pileri Alessandro , Massaia Massimo 
Published: March 2008

Summary. T cells in multiple myeloma (MM) patients are highly susceptible to activation with the anti‐CD3 monoclonal antibody (mAb) OKT3. When short‐term OKT3 stimulation is carried out on bone marrow mononuclear cells (BMMC), large numbers of CD3+CD25+HLA‐DR+ cells are rapidly generated and autologous malignant plasma cells are killed. OKT3 may thus be exploited in autologous bone marrow transplantation (ABMT) to purge residual plasma cells and simultaneously activate T cells to induce graftversus‐leukaemia‐like (GVL‐like) activity upon reinfusion. However, the possible impact of ex‐vivo short‐term OKT3 stimulation on haematological recovery is unknown. The aim of this work was to investigate the effect of OKT3 stimulation in vitro on autologous haemopoietic progenitor cells (HPC) of MM patients. Colony formation by granulocyte‐macrophage progenitor cells (granulocyte‐macrophage colony‐forming units, CFU‐GM) was highly suppressed, although supernatants of OKT3‐activated T cells contained up to 2500 pg/ml of granulocyte‐macrophage colonystimulating factor (GM‐CSF). T cell depletion completely prevented this suppression. Neutralizing antibodies against TNF‐α, TNF‐β and IFN‐γ (which are also produced by OKT3‐activated MM T cells) did not prevent it, and Transwell cultures showed that cell‐to‐cell contact was the main mechanism involved. OKT3‐activated T cells also suppressed erythroid burst‐forming units (BFU‐E) and CFU‐GM generation from HPC responsible for long‐term maintenance of in vitro myelopoiesis.When tested on normal allogeneic BM, MM supernatants of OKT3‐stimulated BMMC partially suppressed the generation of day 7 CFU‐GM, but had no effect on day 14 CFU‐GM.These data indicate that short‐term stimulation of BMMC with OKT3 can be used to generate anti‐tumour effector T cells for autologous adoptive immunotherapy. It is not a feasable approach for ex‐vivo purging and activation procedures in ABMT because of its potent inhibition of autologous haemopoiesis.
P‐glycoprotein expression on acute myeloid leukaemia blast cells at diagnosis predicts response to chemotherapy and survival
Authors: Wood P. , Burgess R. , MacGregor A. , Yin J. A. Liu 
Published: March 2008

SummaryP‐glycoprotein (Pgp) expression, which is associated with the multi‐drug resistance (MDR) phenotype, has been reported to be a useful predictor of treatment outcome in acute leukaemia. We have examined the expression of Pgp on acute myeloid leukaemia (AML) cells in 54 newly diagnosed patients, using a novel streptavidin‐biotin complex (ABC) technique, 56% of patients at diagnosis were positive for Pgp with JSB‐1, a monoclonal antibody that binds to an internal epitope of Pgp. All patients received intensive induction chemotherapy. Post‐remission treatment consisted of futher chemotherapy ± bone marrow transplantation. Complete remission (CR) rates were significantly lower in the Pgp positive group than in the Pgp negative group (60%v 92%; P= 0.02). The overall survival for Pgp‐positive patients was significantly shorter (329 v 534d, P= 0.004), disease‐free survival was also reduced but the difference was not statistically significant (median 277 v 522d, P= 0.16). In this study CD34 expression was not predictive of response to chemotherapy nor was it associated with Pgp expression. Our results confirm the prognostic value of Pgp expression in AML at diagnosis and we suggest that Pgp could be a useful therapeutic target for reversing multi‐drug resistance. Furthermore, our simple and sensitive method of detecting Pgp should enable widespread testing to be performed.
Peripheral T cell receptors αβ and γδ in patients with Hodgkin's lymphoma
Authors: Akan Hamdi , Beksaçl Meral , Aydoǧgdu Ismet , Koçl Haluk , Ilhan Osman , ÖZcan Muhit 
Published: March 2008

SummaryAntigen recognition by T cells is determined by an antigen specific T cell receptor (TCR). Two heterodimeric TCR structures associated with CD3 have been defined: TCR αβ and TCR γδ. TCR αβ and its function are well described but the role of TCR γδ in normal and lymphoproliferative disorders is not well established. In newly diagnosed or relapsed/refractory Hodgkin's disease (HD), a disease associated with defective T cell functions and increased sIL‐2R, We determined levels of seven TCR αβ variable regions [βV5(a), βV5(b), βV6(a), βV12(a), αβV(a), αV2(a)] and TCR γδ by using monoclonal antibodies (MCA). TCR γδ levels did not show any difference, but several variable regions of the TCR αβ differed when groups are compared with each other and the control group.
A case of severe neonatal thrombocytopenia with schizencephaly associated with anti‐HPA‐1 b and anti‐HPA‐2a
Authors: Kuijpers Robert W. A. M. , Anker John N. van den , Baerts Wim , Borne Albert E. G. Kr. von dem 
Published: March 2008

SummaryWe report a family with a neonate who was severely damaged by intracranial haemorrhages. These probably occurred before the 20th week of gestation. The neonate had a moderate thrombocytopenia. In the maternal serum anti‐HPA‐1b and anti‐HPA‐2a alloantibodies were detected. Third‐generation assays were applied to identify the alloantibodies. No other cause for the bleeding was found. Probably the combination of anti‐HPA‐1b and anti‐HPA‐2a alloantibodies, directed against the platelet fibrinogen receptor and the von Willebrand receptor, respectively, induced a thrombocytopenia and a thrombocytopathy.
The painful crisis of homozygous sickle cell disease: clinical features
Authors: Serjeant Graham R. , Ceulaer Charles D. E. , Lethbridge Rosemary , Morris Joanne , And Atul Singhal , Thomas Peter W. 
Published: March 2008

SummaryThe details of onset, perceived precipitating factors, associated symptoms, and pain distribution in the painful crisis of homozygous sickle cell (SS) disease have been prospectively recorded in 183 painful crises in 118 patients admitted to a day‐care centre in Kingston, Jamaica. Painful crises developed most frequently between 3 p.m. and midnight, most commonly affected patients aged 15‐29 years, affected the sexes equally, and were not obviously influenced by menstrual cycle. Of the perceived precipitating factors, skin cooling occurred in 34%, emotional stress in 10%, physical exertion in 7%, and pregnancy in 5% of women of child‐bearing age. Cold as a precipitant was not less common in patients with more subcutaneous fat. Pain affected the lumbar spine in 49%, abdomen in 32%, femoral shaft in 30%, and knees in 21%. There was a highly significant excess of bilateral involvement in limb and rib pain. Recurrent painful crises occurred in 40 patients but showed no evidence of involving similar sites on successive occasions. Abdominal painful crises were associated with abdominal distention in 18 (31%) and with referred rib pain in a further 15 (26%) of crises. Fever was common even in apparently uncomplicated painful crises, suggesting that fever is characteristic of the painful crisis itself and not necessarily indicative of infection. Following investigation and treatment in a day‐care centre, over 90% of patients returned home.
rh‐Erythropoietin stimulates immature reticulocyte release in man
Authors: Major Attila , Bauer Christian , Breymann Christian , Huch Albert , Huch Renate 
Published: March 2008

SummaryThe pharmacodynamics of single intravenous dosing with recombinant human erthropoietin (rhEPO) was investigated in eight healthy volunteers (150U/kg, n = 2; 300 U/kg, n = 6) with respect to reticulocyte subdivisions (by fluorescence flow cytometry) and serum ferritin over 6.5 d. The present study shows that bolus rhEPO injection produces an immediate release of high and middle fluorescence (immature) reticulocytes with a high RNA content from the marrow into the circulation, whereas the low fluorescence (more mature) reticulocytes were at first not affected. Serum ferritin decreased markedly within 24 h, reaching a nadir 50% of baseline after 120h (5 d), with no increase in haemoglobin. Our data suggests that rhEPO triggers premature expulsion of immature reticulocytes from the bone marrow into the circulation independent of its effect in stimulating erythropoiesis and that rhEPO has an effect on serum ferritin concentration which in this dynamic situation is dependent not only on the iron stores.
Detection and significance of bone marrow infiltration at the time of autologous bone marrow transplantation in Hodgkin's disease
Authors: Chopra R. , Wotherspoon A. C. , Blair S. , McMillan A. K. , Mills W. , Fielding A. K. , Linch D. C. , Goldstone A. H. 
Published: March 2008

SummaryBilateral iliac crest biopsies were performed at the time of bone marrow (BM) harvest in patients with poor‐risk Hodgkin's disease (HD) undergoing autologous bone marrow transplantation (ABMT). 67 consecutive patients with normal trephine biopsies (58 unilateral; nine bilateral) taken 2 weeks prior to harvest were studied. Nine (13%) of patients had BM infiltration with HD on the harvest biopsies. These patients had all previously had only unilateral biopsies. Three patients did not proceed to ABMT because disease progression became clinically apparent, but the remaining six patients were infused with involved marrow. One patient died 6 weeks post ABMT, with no evidence of disease at post‐mortem. One patient showed no response to ABMT and four patients either had a partial or complete response to ABMT. Of the responders, three patients are now in complete remission at 53, 39 and 33 months past ABMT.
Serum thymidine kinase in congenital dyserythropoietic anaemia type III
Authors: Sandströum Herbert , Wahlin Anders , Eriksson Mikael , Bergström Ingmar 
Published: March 2008

SummarySerum thymidine kinase (TK) was determined in a family with congenital dyserythropoietic anaemia type III (CDA, type III). 20 patients and 10 of their healthy siblings were investigated. Elevated TK was found in all 20 patients (median 56.2 U) but their healthy siblings had normal values (median 2.65 U). We suggest that determination of TK should be used for discrimination between healthy siblings and individuals affected by CDA type III when bone marrow examination is not suitable.
A function of CD10 on bone marrow stroma
Authors: Delikat Sylvie E. , Galvani David W. , Zuzel Mirko 
Published: March 2008

Summary. Bone marrow (BM) stromal cells express CD10 (cALLA), a surface antigen now known to be a neutral endopeptidase (NEP‐24.11). The function of CD10 in BM stroma is unknown, although purified NEP‐24.11 is known to degrade different substrates including interleukin 1β (IL‐1β).We have therefore employed a CD10‐positive BM stromal cell line (L2AK) which proliferates in response to IL‐1β to test the hypothesis that degradation of this cytokine is one of the functions of stromal CD10.We first showed that [3H]thymidine incorporation by L2AK cells is enhanced by IL‐1β in a clear dose‐dependent manner. Addition of the CD10 inhibitor, phosphoramidon, together with IL‐1β resulted in a left shift in the dose‐response curve which corresponded to a 10‐fold potentiation of the IL‐1β effect.These results indicate that CD10 on bone marrow stromal cells can degrade IL‐1β and therefore provide a local control of the effects of this, and possibly other, growth factor(s).
A patient with multiple myeloma and respiratory insufficiency due to accumulation of paraprotein in the alveolar space
Authors: Meijer W. G. , Kooy M. Van Marwijk , Ladde B. E. 
Published: March 2008

SummaryWe describe a patient with multiple myeloma and respiratory insufficiency. Autopsy revealsed acumulation of igG‐kappa paraprotein in the alveolar space. The clinical and pathological presentation are typical for secondary pulmonary alveolar proteinosis. Attention is focussed on the possibility of secondary pulmonary alveolar proteinosis as cause for dyspnoea in patients with haematological malignancies.
Immunophenotype of c‐kit cells in normal human bone marrow: implications for the detection of minimal residual disease in AML
Authors: Macedo A. , Orfao A. , Martianez A. , Vidriales M. B. , Valverde B. , Loapez‐Berges M. C. , Miguel J. F. San 
Published: March 2008

Summary. In the present study, seven normal human bone marrow samples from healthy volunteers have been analysed in order to investigate the immunophenotypic characteristics of the normal CD117+ cells and their utility for the detection of minimal residual disease in 71 acute myeloid leukaemia patients.Our results show that most of normal BM CD117+ cells coexpress the HLADR and the myeloid associated CD33 antigen. In addition, almost half of CD117+ cells are CD34+, these cells displaying a different FSC/SSC distribution when compared to the CD117+/CD34− cells. No CD117+/CD15+ and CD117+/CD10+ cells were detected and very few CD117+ cells (<1 × 10−3) expressing the HLADR−/CD34−, CD33+/HLADR− and CD34+/HLADR− phenotypes were found to be present in normal BM. In contrast, from the 71 AML patients analysed, 34 had CD117+/CD15+ blast cells and eight had the CD117+ phenotypes detected at low frequencies (<1 × 10−3) in normal BM.In summary, the present study shows that the use of the CD117 antigen in different monoclonal antibodies combinations may be of great help for the detection of minimal residual disease in a high proportion of AML cases, especially in those patients displaying the CD117+/CD15+ phenotype, because cells coexpressing both antigens in normal BM, if present, are at very low frequencies.
Gender and treatment outcome in childhood lymphoblastic leukaemia: report from the MRC UKALL trials*
Authors: Chessells J. M. , Richards S. M. , Bailey C. C. , Lilleyman J. S. , Eden O. B. 
Published: March 2008

Summary. We have examined the factors influencing prognosis in over 4000 children with acute lymphoblastic leukaemia (ALL) aged 1–14 who have been treated on consecutive MRC UKALL trials from 1972 to 1990. During this time the results of treatment have improved steadily but are consistently superior in girls when compared with boys; the 5‐year event‐free survival in girls improving from 51% to 71% and in boys from 31% to 57%. These results were independent of age and presenting leucocyte count. Boys not only had a testicular relapse rate of 10% but an excess of bone marrow relapse, particularly evident after 2 years from diagnosis. Other prognostic factors included organomegaly and the morphology of leukaemic blast cells; immuno‐phenotype of the leukaemia, however, had no independent significance after allowance for age, sex and leucocyte count.The influence of sex on prognosis was reaffirmed when we examined various methods of identifying children at highest risk of treatment failure for whom alternative therapy such as bone marrow transplantation might be justified. In MRC UKALL X children had been deemed ‘high risk’ on the basis of leucocyte count alone, but with further follow‐up it has become apparent that girls with an initial leucocyte count of > 100 × 109/1 have a similar prognosis to boys with a lower count. We therefore derived a risk score based on sex, age and count which has given better discrimination between standard risk (66% 5‐year survival) and poor risk (39%) survival than other methods. This group of worse‐risk children includes 16% of boys but only 3% of all girls.Gender remains an important prognostic factor in UKALL trials and there are very few girls who are at highest risk of treatment failure. The reasons for this remain unclear, but the pattern of relapses suggests that boys more often get inadequate systemic therapy. We postulate that the reasons for treatment failure may relate to sensitivity to continuing (maintenance) chemotherapy.
The determination of spontaneous megakaryocyte colony formation is an unequivocal test for discrimination between essential thrombocythaemia and reactive thrombocytosis
Authors: ROLOVIC ZORAN , BASARA NADEZDA , GOTIC MIRJANA , SEFER DIJANA , BOGDANOVIC ANDRIJA 
Published: March 2008

Summary. Spontaneous colony formation from bone marrow megakaryocyte progenitors (BMsCFU‐Mk) was studied in 24 patients with essential thrombocythaemia (ET), 20 patients with reactive thrombocytosis (RT), 20 patients with polycthaemia rubra vera with thrombocytosis (PRVtr), 16 patients with chronic myeloid leukaemia with thrombocytosis (CMLtr) and 18 normal control subjects (C).The culture medium which was used in the methylcellu‐lose assay in vitro contained 30% of plasma from a single patient with hereditary haemochromatosis. Remarkable BMsCFU‐Mk growth was recorded in all patients with ET but in none with RT or in C. BMs‐CFU‐Mk were present in 11/20 patients with PRVtr and 7/16 patients with CMLtr.Spontaneous bone marrow erythroid progenitors (BMsBFU‐E) were also determined in these patients. BMsBFU‐E were found in 21/24 patients with ET and none in the patients with RT and C. All patients with PRVtr and one patient with CMLtr showed BMsBFU‐E.We conclude that our implementation of the in vitro methylcellulose assay allows the BMsCFU‐Mk to be used as an unequivocal test for discrimination between ET and RT which has not been shown in previously published studies.In addition, we present evidence that in 10 patients BMsCFU‐Mk and/or BMsBFU‐E growth in the test persisted after long‐lasting haematological remission.
GST‐7T and P‐170 co‐expression in multiple myeloma
Authors: PETRINI MARIO , SIMONE DANIELA DI , FAVATI ADRIANA , MATTII LETIZIA , VALENTINI PAOLA , GRASSI BRUNO 
Published: March 2008

Summary. Bone marrow samples from 40 patients affected by multiple myeloma either treated or untreated were examined for expression of glutathione‐S‐transferase n (GST‐TT), P‐glycoprotein and the protein product of ras oncogenes family, p‐21, on plasma cells, by immuno‐cytochemical detection. 72% of evaluated samples were positive for P‐170 and 82% for GST‐7T without any correlation with clinical or prognostic parameters. A significant relationship between GST‐7T expression and P‐l 70 positivity was found and co‐expression was observed in 91% of evaluated samples.Expression of P‐170 and GST‐TT was found both in treated and untreated patients. However, patients evaluated before and after therapy showed an increase in the percentage of plasma cells positive for GST‐7T or P‐170 or both. Expression of p‐21 was not associated with these mechanisms of drug resistance.These data suggest that different resistance mechanisms are present in multiple myeloma.
Immunohistochemical characterization of intact stromal layers in long‐term cultures of human bone marrow
Authors: WILKINs B. S. , JONES D. B. 
Published: March 2008

Summary. We have performed an immunohistochemical study of intact adherent layers of human long‐term bone marrow cultures (hLTBMC) in order to characterize the cell types present. Our panel of antibodies was selected to demonstrate various mesenchymal and haemopoietically derived cell types and to assess the presence of molecules of potential importance as adhesive ligands between haemopoietic cells and stroma.Subpopulations of fibroblasts and macrophages were identified which differed in immunophenotype. We were able to demonstrate modulation of fibroblast and extracellular matrix immunophenotypes between 2 and 12 weeks in culture. Stromal cells and matrix expressed a wide variety of antigens of potential importance in haemopoietic cell adhesion, but no ICAM‐1, 2 or 3 could be demonstrated to correspond to the strong LFA‐1 expression seen in haemopoietic precursor cells.No localization of antigen expression by stromal elements was found to account for the formation of haemopoietic foci at particular sites. However, granulocyte‐predominant foci preferentially occupied the interstices and margins of structures which appeared to be vascular arrays.
Transplanted sickle‐cell disease patients with autologous bone marrow recovery after graft failure develop increased levels of fetal haemoglobin which corrects disease severity
Authors: FERSTER A. , CORAZZA F. , VERTONGEN F. , BUJAN W. , DEVALCK C. , FONDU P. , COCHAUX P. , LAMBERMONT M. , KHALADJI Z. , SARIBAN E. 
Published: March 2008

Summary. Bone marrow transplantation (BMT) is the only curative therapy for sickle‐cell disease (SCD), but is not devoid of failure risk. Nine patients with severe SCD were grafted in our institution between 1988 and 1993. Six patients successfully engrafted, but three failed to engraft and had delayed autologous recovery.All patients had, prior to BMT, low levels of fetal haemoglobin (HbF ≤3.5%). No change in HbF occurred in successfully grafted patients. In the three patients with graft failure HbF increased and remained persistently present at a high level (≥22%) 14 months, 16 months and 39 months post BMT, although two of the three patients were homozygous for either the Benin or the Central African Republic haplotype, a characteristic associated with low HbF level. Of interest, these three previously severely affected patients remain free of vaso‐occlusive events.The mechanism responsible for the expression of high levels of HbF in our three patients with graft failure is not understood, but it protects them from the recurrence of severe vaso‐occlusive crises.