bluuebunny/crossref_metadata_2025_split huggingface dataset:
Elevated levels of soluble factors in the cerebrospinal fluid in patients with adult T‐cell leukaemia complicated with meningeal infiltration
Authors: Uozumi Kimiharu , And Shuichi Hanada , Arima Terukatsu 
Published: March 2008

SummaryWe measured some soluble factors in the cerebrospinal fluid (CSF) of patients with adult T‐cell leukaemia (ATL) complicated with meningeal infiltration. Interleukin‐4 (IL‐4) was not detectable in the CSF of all cases with meningeal infiltration. Interleukin‐6 (IL‐6) was detected in a few patients with ATL. Measurement of IL‐4 and IL‐6 in CSF had no diagnostic value for meningeal infiltration of ATL cells. Soluble CD4 (sCD4) was highly elevated in all ATL patients with meningeal infiltration. Soluble interleukin‐2 receptor (sIL‐2R; sCD25) in CSF was markedly elevated in 13/18 ATL patients (72.2%) with meningeal infiltration. Levels of sCD4 and sCD25 in the CSF of ATL patients with central nervous system (CNS) symptoms were significantly higher than those of non‐ATL patients with CNS symptoms. These observations indicate that sCD4 and sCD25 in the CSF are probably associated with meningeal infiltration of leukaemia cells that expressed CD4 and CD25 on the surface membrane and new markers for the meningeal infiltration of ATL cells.
Long‐term treatment with interferon‐α2b for severe pruritus in patients with polycythaemia vera
Authors: Muller E. W. , Wolf J. Th. M. de , Egger R. , Wijermans P. W. , Huijgens P. C. , Halie M. R. , Vellenga E. 
Published: March 2008

Summary. Pruritus is a major clinical problem in patients with polycythaemia vera (PV). Conventional symptomatic treatment is unsatisfactory. Recently, a favourable effect of interferon‐α on pruritus in patients with PV has been reported. Also, interferon‐α suppresses the increased haemopoiesis in PV. However, long‐term treatment with interferon‐α may be hampered by side‐effects and the inconvenience of chronic subcutaneous injection therapy.We conducted a long‐term study (median follow‐up 13 months) of the efficacy and tolerability of interferon‐α in 15 patients (mean age 68 years) with PV and severe pruritus. Six patients were evaluable after 1 year. Pruritus significantly improved in 12/15 patients. Haematological control improved, as evidenced by a decreased number of phlebotomies from a mean of 4.3 in the year before the study to 1.8 while on interferon‐α. Leucocyte and platelet numbers also decreased significantly. Five patients (33%) did not tolerate interferon‐α. The effects of interferon‐α could not be ascribed to an inhibitive effect on histamine production or to the disappearance of the abnormal erythroid progenitor clone, because erythropoietin‐independent erythroid colony formation persisted during interferon‐α treatment. We conclude that long‐term interferon‐α treatment is feasible and effectively relieves pruritus in patients with PV, but side‐effects are an important concern. The optimal dose regimen that is well tolerated, relieves pruritus, and offers satisfactory haematological control at the same time remains to be established.
Attenuated‐dose idarubicin in acute myeloid leukaemia of the elderly: pharmacokinetic study and clinical results
Authors: LEONI F. , CIOIXI S. , GIULIANI G. , PASCARELLA A. , CAPORALE R. , SALTI F. , CERVI L. , FERRINI P. Rossi 
Published: March 2008

AML in the elderly is characterized by intrinsic biological features implying an enhanced chemoresistance. Intensive chemotherapy should be the treatment of choice, but the standard doses could induce unacceptable rates of aplastic deaths. We evaluated the efficacy of an induction protocol with attenuated‐dose idarubicin (IDA) 8 mg/m2 for 3 d plus cytarabine and etoposide in 26 AML patients aged >60. 18 patients (69%) achieved CR, five (19%) were non‐responders and three (12%) died during induction. To compare the pharmacokinetics of IDA between elderly and young patients, we assayed daily the serum level of the drug and of its metabolite (idarubicinol, IDAol) in a group of eight elderly patients who received a dose of 8 mg/m2 (group A) and in a group of nine younger AML patients treated with 12 mg/m2 (group B). The apparent terminal half‐life of IDAol was significantly longer in the elderly than in the younger patients (mean half‐life 59–7h versus 41–4h, P< 0–05). The values of the area under the serum concentration curve of IDAol indicated that the two patient groups received a very similar exposure to the drug despite the different doses.In conclusion, this protocol, based on attenuated doses of IDA, compares well with the results obtained previously in similar age‐matched patient series.
C‐myc amplification, double minutes and homogenous staining regions in a case of AML
Authors: FEGAN C. D. , WHITE D. , SWEENEY M. 
Published: March 2008

Summary. c‐myc amplification is usually associated with lymphoid malignancies and Burkitt's lymphoma in particular. We present a case of AML with c‐myc amplification which was associated with homogenous staining regions (hsr) and double minutes (dmin). The administration of GCSF following induction chemotherapy resulted in a marked increase in blast numbers. The GCSF was stopped and further courses of chemotherapy given, which resulted in complete remission. The patient relapsed 7 months after diagnosis and failed to go into a second remission with reinduction therapy.We conclude that c‐myc amplification is a rare event in AML, but may be associated with chemotherapy resistance and a poor prognosis, are as dmins and hsr. Growth factors should be used with caution in these patients.
Hereditary xerocytosis: a report of six unrelated Spanish families with leaky red cell syndrome and increased heat stability of the erythrocyte membrane
Authors: CORRONS J. LL. VIVES , BESSON I. , AYMERICH M. , AYALA S. , ALLOISIO N. , DELAUNAY J. , GONZALEZ I. , MANRUBIA E. 
Published: March 2008

Summary. Hereditary xerocytosis (HX) is a rare haemolytic disease due to dehydrated red blood cells (RBCs). A unique feature of this syndrome is that affected members often show normal or near normal haemoglobin levels despite clinical and laboratory evidence of mild to moderate haemolysis. The diagnostic clue is the association of markedly increased RBC Na++K+ fluxes with low total cation (Na++K+) content. 11 patients of six unrelated families of Spanish origin with HX have been studied from clinical, genetical and biological points of view. In addition, we have investigated the sensitivity of RBC membrane to heat at three different incubation times (15, 30 and 60min) and two different temperature values (46°C and 49°C). Under these conditions control RBCs (50 normal subjects) exhibited at 49°C and 30min a maximum of 30% fragmented RBCs. This value increased to 80% after 60min of incubation. In contrast, patients with HX showed significantly lower percentages of fragmented RBCs at both 30 and 60min of incubation (maximum 10% and 30%, respectively). In an attempt to determine if increased heat stability was unique to HX RBCs, several other congenital membranopathies with haemolytic anaemia were also studied. The degree of fragmentation, except in one case of HPP (which was strongly increased), did not differ from the control group. Electrophoretic studies of membrane proteins performed in RBCs of all the patients with HX did not explain any qualitative nor quantitative abnormality.In addition to its physiopathological interest, study of RBC heat stability, together with other haematological parameters (increased MCHC and decreased RBC osmotic fragility), may be useful for HX diagnosis, especially in laboratories which are not equipped to evaluate RBC membrane permeability.
Heterogeneity in cell proliferation and expression of p53 and bcl‐2 during the indolent phase of germinal centre cell lymphoma: an explanation for clinical variability
Authors: BARRANS S. , RANDERSON J. , EVANS P. , BLYTHE D. , SHIACH C. , CHILD J. A. , MORGAN G. , JACK A. S. 
Published: March 2008

Summary. Germinal centre cell lymphomas (GCCL) show a wide range of clinical outcomes from persistent indolent disease to large cell transformation. To investigate possible mechanisms of this heterogeneity, a combined morpho‐metric and immunohistological study of p53, bcl‐2 and cell proliferation was carried out. There was wide variation in p53 expression between biopsies and between individual follicles in the same tumour. A similar pattern of variation was seen using the cell‐cycle marker MIB1, but this did not correlate with p53 expression. Even in cases in which a t(14:18) was demonstrated by PCR, variation occurred in the number of cells expressing bcl‐2.On the basis of these results, we suggest that the probability of the clonal expansion of GCCL tumour cells carrying additional genetic abnormalities depends on a complex interaction of cell proliferation with p5 3 and bcl‐2 expression, and that this may account for variation seen in the clinical behaviour seen in this group of tumours.
The effect of interleukin‐12 in ex‐vivo expansion of human haemopoietic progenitors
Authors: BERTOLINI FRANCESCO , SOLIGO DAVIDE , LAZZARI LORENZA , CORSINI CHIARA , SERVIDA FEDERICA , SIRCHIA GIROLAMO 
Published: March 2008

Summary. We evaluated progenitor cell proliferation in cultures supplemented by different cytokine combinations in the presence or absence of IL‐12. In cultures of low density cells, cytokine combinations including IL‐12 were associated to a greater proliferation (up to 6.7 ± 2.5 CFU‐GM fold expansion). However, in cultures of purified CD34+ cells the more efficient cytokine combination (147 ± 49 CFU‐GM fold expansion) was SCF, IL‐3, IL‐11 and MlP‐la, and the addition of IL‐12 did not further enhance expansion of progenitors.These results indicate that accessory cells, lost in CD34+ cell purification, could be in part responsible for IL‐12 effect on progenitor cell proliferation. In CD34+ cell cultures the addition of IL‐12 led to CD19 mRNA generation, suggesting that IL‐12 acts on haemopoietic cells with both myeloid and lymphoid potential.
A simple and sensitive method for determining plasma cell isotype and monoclonality in bone marrow using flowcytometry
Authors: van Zaanen H. C. T. , Vet R. J. W. M. , de Jong C. M. , von dem Borne A. E. G. Kr. , van Oers M. H. J. 
Published: March 2008

Summary. In this paper we describe a new, rapid and sensitive method to determine plasma cell isotype and clonality in bone marrow using flowcytometry. With the use of a new fixation and permeabilization reagent (Permeafix®), which preserves cell structure and morphology, and a monoclonal antibody (Mab) specific for plasma cells (B‐B4), it has become possible to specifically select plasma cells and to determine the cytoplasmatic immunoglobulins by flowcytometry.Thirty successive bone marrow aspirates from multiple myeloma patients and patients with MGUS were studied as well as 10 bone marrow samples from patients with reactive plasmacytosis. Each sample was analysed both by immunofluorescence on cytospin smears and FACS analysis. There were no discrepancies between plasma cell isotype as determined by FACS and cytospin. Moreover, FACS analysis was shown to allow detection of very low numbers of plasma cells and to determine whether these plasma cells are mono‐or polyclonal. Possible applications are discussed.
Use of central venous catheters in children with severe congenital coagulopathy
Authors: Liesner R. J. , Vora A. J. , Hann I. M. , Lilleymann J. S. 
Published: March 2008

Summary From two U.K. centres 23 children with severe congenital coagulopathy had a total of 27 port‐a‐cath devices inserted to facilitate factor VIII or IX prophylaxis (eight patients), domiciliary therapy (seven patients), immunotolerance (four patients), or a combination thereof (four patients). Six children had a factor VIII inhibitor at the time of insertion. The mean age at operation was 30 months, with a range of 9–76 months. The cumulative length of follow‐up is 639 months with a mean of 27–8 months and a range of 5–79 months.Haemostasis was achieved peri‐ and post‐operatively with high‐purity concentrate in the majority of patients without an inhibitor. All those with an inhibitor had porcine factor VIII, except one who had recombinant factor Vila.The post‐operative complication rate was 27% (6/23): three had a port‐site haematoma (one required removal and replacement), two had post‐operative infection, and one had swelling caused by extravasation.To date there have been 13 documented infections in 10/ 23 patients (five with inhibitor): a rate of 0–24 per follow‐up year or 0–67 per 1000 patient‐days. Six were caused by Gram‐positive and seven by Gram‐negative organisms. Six infections could not be eradicated by antibiotics and the port‐a‐cath system had to be removed; in three it was replaced by a second port‐a‐cath.Although there are risks involved in the use of port‐a‐caths in this population, both clinicians and parents involved in the care of these children believe that the benefits are considerable and the potential hazards are acceptable.
In vitro platelet ageing at 22°C is reduced compared to in vivo ageing at 3 7°C
Authors: Holme S. , Heaton A. 
Published: March 2008

Summary .In these studies, platelet ageing during in vitro at 22°C was compared with in vivo ageing using isotope labelling. Paired fresh and 5‐d‐stored platelets had a mean residual life‐span (MRL) of 4–8 ± 0–7d and 3–2 ± 0–9 d, respectively. After 2–1 ± 0–4 d in vivo circulation, the MRL of the fresh platelets was equivalent to that of the 5‐d‐stored in vitro platelets. This suggests that platelet ageing for 5 d in vitro at 22°C corresponds to 2–1 d in vivo ageing at 37°C. Thus, the relative ageing at 22°CC in vitro was (2.1 d/ 5d) = 0–42 of that at 37°C in vivo. A similar ageing ratio (0–44) was obtained by measurement of the decrease in MRL during storage at 22°C of platelets stored for 1, 5, 7, 10 and 14 d relative to the decrease in MRL of fresh platelets in vivo.ATP turnover rate at 22°C was compared to the rate of 37°C by measurement of the rates of platelet oxygen consumption and lactate production in vitro. In vitro ATP turnover at 22°C versus 37°C, was found to be 10–5 ± 10 versus 21–6 ± l.4/μmol/1012plts/min, respectively. Thus, the ATP turnover ratio (0–48) at these two temperatures suggests that the relative decrease in ageing at 22°C compared to 37°C is similar to the relative decrease in metabolic rate at this temperature.
Interleukin‐3 priming in acute myeloid leukaemia patients
Authors: Tafuri Agostino , Felice Lidia de , Goodacre Angela , Fenu Susanna , Petrucci Maria Teresa , Valentini Tiziana , Alimena Giuliana , Petti Maria Concetta , Meloni Giovanna , Mandelli Franco , Andreeff Michael 
Published: March 2008

Summary Several studies have demonstrated that G‐CSF, GM‐CSF and, in particular, IL‐3 can effectively recruit acute myeloid leukaemia (AML) blasts into the cell cycle, resulting in a significant increase in cytosine‐arabinoside (Ara‐C) mediated cytotoxicityin vitro. Since IL‐3 has shown biological and clinical activity, we investigated the cell kinetic effects of rIL‐3 and high‐dose Ara‐C/idarubicin in three patients with refractory AML selected for the presence of chromosome 7 monosomy; this enabled differentiation between the effects of IL‐3 on leukaemic and on normal cells. Thein vivo administration of rhIL‐3 (250μ/m2 d s.c. for 6–10 d) recruited AML blasts into the cell cycle in two of the three patients, and this effect resulted in an increase inin vitro growth of clonogenic cells (CFU‐L) and of their S‐phase fraction. The percentage of leukaemic cells with monosomy 7 increased only in the two cases who showed a proliferative response. Normal cells were not recruited, even when rhIL‐3 was administered for up to 10 d.In vitro studies showed an increased Ara‐C cytotoxicity on clonogenic AML cells, in particular with LL‐3 plus GM‐CSF, thus confirming the priming effects of IL‐3 in the two responding cases.The results of this study suggest that rhIL‐3 can selectively recruit leukaemic cells into the cell cycle. Although leukaemic blasts can be sensitized to Ara‐C, other mechanisms of primary blast resistance may limit the clinical benefit of kinetic‐based approaches.
Haemopoietic growth factor production by normal and aplastic anaemia stroma in long‐term bone marrow culture
Authors: Gibson F. M. , Scopes J. , Daly S. , Ball S. , Gordon‐Smith E. C. 
Published: March 2008

Summary. Defective marrow stroma, or microenvironment, have been proposed as one of several mechanisms to account for bone marrow failure in aplastic anaemia (AA). This could involve defects in positive‐ or negative‐acting haemopoietic regulator expression by AA stroma, or alteration of normal stroma‐stem cell interactions.We have used a sensitive bioassay to investigate production of granulocyte‐colony stimulating factor (G‐CSF), granulocyte‐macrophage‐colony stimulating factor (GM‐CSF), interleukin (IL)‐3, IL‐6 and stem cell growth factor (SCF), by normal and AA stroma In long‐term bone marrow culture (LTBMC). LTBMC were grown to confluence, irradiated and harvested to yield a single cell suspension. These cells were cocultured with normal target bone marrow mononuclear cells (BMMC), or CD34+ cells, in clonogenic assays, in the absence of exogenous cytokines. Cytokines responsible for the colony‐stimulating activity (CSA) and burst‐promoting activity (BPA) produced by stromal cells were identified by neutralizing antibodies to specific cytokines. All normal stroma populations produced G‐CSF and GM‐CSF, 93% produced IL‐3, 80% produced IL‐6, and 70% produced SCF. Similarly, all AA stroma produced G‐CSF and GM‐CSF, and 71% produced SCF. In contrast, only 71% of AA stroma produced IL‐3 and 36% produced IL‐6. Target cell stimulation was not dependent on direct stroma‐target cell contact, suggesting production of soluble cytokines. However, although both IL‐6 and G‐CSF were detected in LTBMC supernatants by enzyme‐linked immunoassay (ELISA), IL‐3 and GM‐CSF were undetectable, perhaps indicating low‐level local production of these factors.
Retinoic acid inhibits the growth of human myeloma cells in vitro
Authors: Palumbo Antonio , Battaglio Silvano , Napoli Patrizia , Bruno Benedetto , Omedè Paola , Boccadoro Mario , Pileri Alessandro 
Published: March 2008

Retinoic acid has been shown to induce growth inhibition in a variety of cell types including human myeloma cell lines. Bone marrow plasma cells from 31 multiple myeloma (MM) patients were cultured to investigate the activity of 13‐cis‐retinoic acid (cRA), all‐trans‐retinoic acid (tRA), interferon‐α (IFN‐α), interferon‐γ (IFN‐γ), and dexamethasone (DEX), alone or in combination, on in vitro proliferation and immunoglobulin (Ig) secretion. Both cRA and tRA inhibited proliferation: the labelling index (LI) of treated cultures/controls, was 0.47±0.05 (mean ± standard error mean, M ± SEM) P < 0.0001, and 0.67 ± 0.04 (M ± SEM), P < 0.0001, respectively. The inhibitory effect of cRA was significantly superior to tRA (P= 0.0129) and IFN‐α, similar to IFN‐γ and DEX. The combinations of cRA + IFNα, tRA + IFN‐γ, tRA + DEX did not show any synergistic effect on myeloma proliferation. In contrast, the combination cRA + DEX (0.29 ± 0.04, M±SEM) markedly increased the effect of both cRA and DEX used as single agents.Ig synthesis was not significantly affected by CRA, tRA, IFN‐γ and the combination tRA + IFN‐γ, As expected, only IFN‐α (P 0.002) and DEX (P 0.001) inhibited Ig production. The combinations cRA + IFN‐α, cRA‐DEX and tRA + DEX decreased Ig secretion to the same extent as IFN‐α and DEX alone respectively. In conclusion, our data indicate that tRA and especially cRA strongly inhibited plasma cell proliferation but had no effect on Ig synthesis. The combination of cRA + DEX showed the highest degree of inhibitory activity of all cytokines. alone or in combination.
Pollen beetle in the UK; the start of a resistance problem?
Authors: Richardson D. M. 
Published: March 2008

In 2003, the first report of poor control of pollen beetle Meligethes aeneus at a site in South East England in the UK was investigated but resistance to pyrethroid insecticides was not confirmed in subsequent laboratory testing. Bioassays of 26 UK samples of M. aeneus collected in 2004 with the pyrethroid lambda‐cyhalothrin showed little or no divergence from the response expected of a fully susceptible strain. In 2006 samples of pollen beetle from the UK were sent to Germany, and again these were shown to be fully susceptible. In 2007 using test kits supplied by Udo Heimbach, BBA, 19 samples of pollen beetle were tested, again from across the UK. Results indicated that a small number of individuals were fully resistant, surviving the highest dose of lambda‐cyhalothrin tested (0.375 microg/L) after 5‐h exposure at 4 sites, and after 24‐h exposure at 2 of these sites.
Testing Bergmann’s rule in the presence of potentially confounding factors: a case study with three species of Galerida larks in Morocco
Authors: Guillaumet Alban , Ferdy Jean‐Baptiste , Desmarais Eric , Godelle Bernard , Crochet Pierre‐André 
Published: March 2008

AbstractAim  To test Bergmann’s rule (which predicts a larger body size in colder areas within warm‐blooded vertebrate species) in three partially sympatric species of larks (Galerida theklae, Galerida cristata and Galerida randonii) that occur in Morocco.Location  Morocco.Methods  Restriction fragment length polymorphism techniques applied on cytochrome b haplotypes were used to discriminate G. cristata and G. randonii, and to investigate the effects of interspecific hybridization in their contact zone. A comprehensive statistical framework was then designed to test Bergmann’s rule in our three Galerida species (using altitude as a proxy for cold temperatures), while controlling for the possible influence of interspecific hybridization and competition and accounting for spatial autocorrelation. The method we propose is conservative in the sense that potentially confounding factors are adjusted so as to maximize their influence on the variable of interest.Results  Bergmann’s rule was strongly supported in G. theklae and G. randonii. However, body size did not respond to altitude in G. cristata, a result that was not simply explained by species‐specific differences in geographical ranges and altitudinal span. In G. cristata, we detected a tendency for body size to increase with aridity, in agreement with an alternative definition of Bergmann’s rule. However, since G. cristata also hybridizes with G. randonii in a contact zone located in the most arid part of the range of G. cristata, we could not tease apart the relative contribution of selection and hybridization in driving this pattern.Main conclusions  This study highlights the need for careful statistical designs that allow meaningful variables to be picked out from large sets of potential factors. When taking these factors into account, we found that Bergmann’s rule was still strongly supported in two out of the three species examined.