bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long‐term follow‐up of patients with hairy cell leukaemia treated with pentostatin: lymphocyte subpopulations and residual bone marrow infiltration
Authors: Thaler Josef , Grünewald Kurt , Gattringer Claus , Ho Anthony D. , Weyrer Katharina , Dietze Otto , Stauder Reinhard , Fluckinger Thomas , Lang Alois , Huber Heinz 
Published: March 2008

Summary. Peripheral blood lymphocyte (PBL) subsets and bone marrow biopsies were analysed in six patients with hairy cell leukaemia (HCL) treated with 2′‐deoxycoformycin (pentostatin, DCF) according to a phase II trial of the EORTC Leukemia Cooperative Group. All patients responded to DCF with four complete and two partial remissions according to conventional criteria.Within the PBL subsets, major changes concerned the CD4± T cells, which during DCF therapy were distinctly suppressed to nadir values of 0–038–0–18 (median 0–126) × 109/‐1. In five patients these cells returned to normal 3‐0–49–5 (median 14·5) months after the last DCF injection. CD8± cells were decreased to a lesser extent, and NK cell numbers improved during treatment.Bone marrow immunohistology applying the MoAb B‐ly7 demonstrated residual hairy cells (HCs) in all of the six patients following DCF treatment with nadir HC numbers of 0·2–3·0% of bone marrow cells. Immunoglobulin gene rearrangement analysis of DNA obtained from these biopsies showed only germline bands, whereas rearranged bands had been present on the pretreatment specimens. Within the observation period of 15·5–54·0 (median 47·0) months after discontinuation of DCF therapy, immunohistology demonstrated a continuous increase in HC numbers in five of the six patients with clonal rearrangement detectable in bone marrow specimens from three of these patients at last follow‐up date. Although established on the basis of a small number of patients, these data suggest that DCF treatment as currently employed in HCL is unable to eradicate the malignant B cell clone.
Role in growth regulation of cytokines and cytokine receptors in acute lymphoblastic leukaemia expressing myeloid markers
Authors: Komada Yoshihiro , Zhou Yan‐Wen , Zhang Shao‐Li , Azuma Eiichi , Sakurai Minoru 
Published: March 2008

Summary. The biological roles of cytokines and cytokine receptors were examined in acute lymphoblastic leukaemia cells expressing myeloid antigens (My+ ALL). Interleukin‐3 (IL‐3), granulocyte‐colony stimulating factor (G‐CSF), granulocyte‐macrophage‐CSF (GM‐CSF), and low molecular‐weight B‐cell growth factor (LW‐BCGF) could induce DNA synthesis in certain cases of My+ ALL. Whereas in My− ALL the stimulatory effects were shown only with LW‐BCGF. Acute myelogenous leukaemia (AML) cells were activated with multiple cytokines including interleukin‐1 (IL‐1), IL‐3, G‐CSF and GM‐CSF. Specific receptors for IL‐1 and IL‐3 were strongly expressed on both My+ and My− ALL cells. These receptors, however, were weakly detectable on AML cells. Additionally we studied the production of tumour necrosis factor‐α and IL‐1 by leukaemic blasts and found that distinct amounts of both cytokines were released from My+ ALL cells and AML cells, but not from My− ALL cells.The profiles of cytokines and cytokine receptors expressed by My+ ALL showed both similaries and differences to those in My− ALL or AML. The proliferation of My+ ALL cells was dependent on multiple cytokines that would regulate growth and maturation in a lineage‐restricted fashion. These data suggested that My+ ALL cells might originate from uncommitted haematopoietic precursor cells coexpressing features of both lymphoid and myeloid lineages.
Granulocyte‐colony‐stimulating factor induces increased serum levels of soluble interleukin 2 receptors preceding engraftment in autologous bone marrow transplantation
Authors: Dreger Peter , Grelle Karen , Eckstein Volker , Suttorp Meinolf , Müller‐Ruchholtz Wolfgang , Löffler Helmut , Schmitz Norbert 
Published: March 2008

Summary The serum levels of soluble interleukin 2 receptors (sIL‐2R) were determined in 19 patients who received highdose chemotherapy and an autologous or syngeneic bone marrow transplant (BMT) for treatment of Hodgkin's disease (n= 18) or non‐Hodgkin's lymphoma (n= 1). Twelve patients received granulocyte colony‐stimulating factor (G‐CSF) from day 0 or day +1 after autologous BMT until the white blood cell count had been stable for 9 d above 1 × 109/1, the remaining seven patients did not receive growth factors, In all G‐CSF‐treated patients the sIL‐2R levels increased steadily in the early post‐transplant course, even in the absence of infection. This increase was statistically significant 2‐4 d prior to the appearance of leucocytes in the peripheral blood (median 340 pm versus median 256 pm immediately after BMT, P<0.025) and peaked with the appearance of first peripheral blood leucocytes (median 536 pm, P<0.001). Cessation of G‐CSF administration resulted in a decline of sIL‐2R levels. In contrast, five of seven patients without G‐CSF treatment did not exhibit an sIL‐2R increase before or at the time of engraftment. Infection was associated with a rise of sIL‐2R levels. A correlation between sIL‐2R levels and total leucocyte count, lymphocyte count, or CD25 + lymphocyte count was not evident.These data suggest that after autologous BMT G‐CSF induces increased sIL‐2R levels, which occur independent of lymphocyte activation. This may be compatible with involvement of immature bone marrow cells in G‐CSF‐induced sIL‐2R release.
Assessment of graft status following allogeneic bone marrow transplantation for haematological disorders in children using locus‐specific minisatellite probes
Authors: Katz Fay , Hann Ian , Kinsey Sally , Ball Sarah , Morgan Gareth , Chessells Judith 
Published: March 2008

We have examined peripheral blood or bone marrow DNA following allogeneic bone marrow transplantation (BMT) in children suffering from a variety of haematological disorders. Using either locus‐specific minisatellite probes separately or in combination with a Y specific probe for sex‐mismatched transplants, complete haematological chimaerism, autologous reconstitution, or mixed chimaeric states have been defined immediately post‐BMT. We have also been able to identify emerging autologous cells or relapse prior to morphological diagnosis.Forty‐two children, mean age 6.4 years (range 9 months to 15 years), received an allogeneic BMT for: acute lymphoblastic leukaemia (ALL), n= 17; acute myeloid leukaemia (AML), n= 5; biphenotypic leukaemia, n= 1; myelodysplastic syndrome (MDS), n= 5; chronic granulocytic leukaemia (CGL), n= 1; severe aplastic anaemia (SAA), n= 7; familial erythrophagocytic lymphohistiocytosis (FEL), n= 2; beta thalassaemia major (beta thal), n= 1; and juvenile chronic myeloid leukaemia (JCML), n= 3. Immediately post‐transplant, 78% had achieved complete haematological chimaerism, 12% had failed to engraft (DNA analysis confirmed autologous reconstitution) and 10% had mixed chimaerism. SAA was the underlying disease in two of the chimaeric cases, the third case having had a matched unrelated donor (MUD) BMT for MDS. In 3/4 cases which subsequently relapsed, DNA analysis showed re‐emergence of autologous cells (indicative of relapse), prior to their morphological identification. We conclude that DNA analysis using minisatellite probes to assess graft status provides a useful contribution to patient management following allogeneic BMT.
Intestinal iron absorption studies in mouse models of iron‐overload
Authors: Raja K. B. , Simpson R. J. , Peters T. J. 
Published: March 2008

Three mouse strains have been evaluated as suitable models for investigations into the pathogenesis of iron‐overload syndromes.Mice with hereditary heterozygous α‐thalassaemia had moderately raised reticulocyte counts, but were not anaemic and showed little, if any, iron loading. In contrast, mice with homozygous β‐thalassaemia showed microcytic anaemia, reticulocytosis and splenomegaly. Iron‐loading was marked, progressive with age and mainly confined to the spleen. Liver iron‐loading increased until the age of 7–8 weeks, with no further increase over successive weeks. Although intestinal iron absorption was modestly increased due to enhanced mucosal uptake, the majority of the ‘excess’liver and spleen iron could be accounted for by re‐distribution of iron from the erythrocytic compartment.Homozygous hypotransferrinaemic mice, with approximately 1–2% of normal plasma transferrin levels, were markedly anaemic with hypochromic microcytic erythrocytes. Intestinal iron absorption increased 3–4‐fold (predominantly due to changes in mucosal transfer), as compared to wild‐type controls and heterozygotes, and was ascertained to be a major factor causing the marked hepatic iron overload. Heterozygous hypotransferrinaemic mice, with over half normal plasma transferrin levels and a mild degree of hepatic iron loading, showed very similar characteristics to wild‐type controls. Thus, of the three models, hpx/hpx mice showed the greatest enhancement in intestinal iron absorption and net iron‐loading and provides a suitable animal model of spontaneous iron‐overload.Comparison of iron absorption values between the models suggests that reticulocytes cannot account for the enhanced absorption seen in the hpx/hpx mice.
Plasma granulocyte‐colony stimulating factor concentrations ([G‐CSF]) in the early neonatal period
Authors: Russell A. R. Bedford , Davies E. G. , McGuigan S. , Scopes G. J. D. , Daly S. , Gordon‐Smith E. C. 
Published: March 2008

Summary We studied G‐CSF concentrations ([G‐CSF]) at birth and their relationship with neutrophil count, incidence of infection, gestational age, labour, and the presence of maternal pregnancy‐induced hypertension.Plasma [G‐CSF] were significantly elevated in babies with suspected infection and in those of hypertensive mothers, compared to healthy babies delivered by elective caesarian section (median [range] = 3101 [75‐ > 5000] pg/ml and 153 [45–857] pg/ml versus 32 [11–266] pg/ml; P<0·0001); and were unrelated to neutrophil count and gestational age. Initial high concentrations (> 100 pg/ml) declined by 7 d (P<0·0001).
Recombinant human interleukin‐3: pharmacokinetics after intravenous and subcutaneous bolus injection and effects on granulocyte kinetics
Authors: Hovgaard D. J. , Folke M. , Mortensen B. T. , Nissen N. I. 
Published: March 2008

SummaryThe pharmacokinetics of E. coli derived recombinant human interleukin‐3 (rhIL‐3) was studied following intravenous (i.v.) and subcutaneous (s.c.) bolus injection of rhIL‐3. After i.v. bolus injection in eight patients, serum peak levels of 34.5‐135.0 ng/ml were reached, followed by a rapid decline with a t1/2α of 17 ± 2 min and a t1/2β of 59 ± 7 min. After s.c. bolus injection in five patients, the absorption was more prolonged with peak serum levels reached at 2.8 ± 0.4h. Elimination was also more protracted, and serum base‐line levels were reached at 14‐24 h.The immediate effect of rhIL‐3 on peripheral white blood cells was less pronounced and more variable than previously found for G‐ or GM‐CSF. Following i.v. administration, neutrophils showed a moderate drop to median 64% of initial values (range 42‐85%) at median 30 min after injection (range 15‐60 min) at median 30 min after injection (range 15‐60 min) followed by an increase at 24 h to 69‐288% of initial values. Eosinophils dropped to a median nadir of 34% and then gradually increased to maximum values in the range 135‐720% at 18‐24h. The effect of rhIL‐3 was further examined following i.v. injection of autologous 111Indium‐labelled granulocytes in six patients. In steady state, i.v. injection of rhIL‐3 caused a moderate drop in 111Indium activity of peripheral blood within 20 min without tendency to subsequent recovery. No change occurred in the activity over the lungs and liver. The activity over the spleen decreased moderately in two patients. These results are strikingly different from those previously obtained after i.v. injection of rhGM‐CSF.
Bone marrow angiogenesis and progression in multiple myeloma
Authors: Vacca Angelo , Ribatti Domenico , Roncali Luisa , Ranieri Girolamo , Serio Gabriella , Silvestris Franco , Dammacco Franco 
Published: March 2008

SummaryTumour growth is angiogenesis‐dependent. We found a high correlation between the extent of bone marrow angiogenesis, evaluated as microvessel area, and the proliferating (S‐phase) fraction of marrow plasma cells, evaluated as labelling index (LI), in patients with multiple myeloma (MM) and in those with monoclonal gammopathies of undetermined significance (MGUS). Angiogenesis itself was significantly associated with active as opposed to non‐active MM and MGUS. The highest microvessel area accompanied rapidly progressive MM with the highest LI. When a cut‐off value of 2% or greater of the microvessel area was used, most patients with active MM were classified correctly. The risk of active disease in patients with MM increased in parallel with the microvessel area. A causal relationship between plasma cell growth, activity phase in MM and marrow angiogenesis is suggested. Since angiogenesis proceeds in step with the enlargement of plasma cell tumours and the activity phase in MM, its measurement could be a useful prognostic marker in patients with plasma cell proliferative disorders.
Validation of a model to predict survival in elderly patients with acute myeloid leukaemia
Authors: JOHNSON PETER R. E. , RYDER W. DAVID J. , LIU YIN JOHN A. 
Published: March 2008

Summary.Intensive chemotherapy is the treatment of choice for selected elderly patients with acute myeloid leukaemia (AML). We recently developed a model to predict survival, thereby providing objective information upon which to select appropriate therapy for such patients. Such models, however, must be validated on a cohort of patients not used during the development of the model.We have tested the model using a series of 61 elderly patients consecutively treated with intensive chemotherapy.Using several statistical techniques, we have shown that the model is of value in predicting prognosis, though two patients did markedly better than the model prediction. This model may be useful for predicting survival in elderly patients with AML and warrants more extensive validation.
Interleukin‐11 (IL‐11) acts as a synergistic factor for the proliferation of human myeloid leukaemic cells
Authors: Lemoli Roberto M. , Fogli Miriam , Fortuna Alessandra , Amabile Marilina , Zucchini Patrizia , Grande Alexis , Martinelli Giovanni , Visani Giuseppe , Ferrari Sergio , Tura Sante 
Published: March 2008

Summary. Interleukin‐11 is a stromal cells derived cytokine which stimulates the proliferation of primitive haemopoietic progenitor cells. For this paper we have studied the constitutive expression of IL‐11 mRNA in a panel of well‐known leukaemic cell lines and samples from AML patients at diagnosis. Moreover, the same cellular populations were evaluated for their proliferative response to recombinant‐human‐(r‐hu) IL‐11 alone and combined with r‐hu‐IL‐3, granulocyte‐macrophage colony stimulating factor (GM‐CSF) and stem cell factor (SCF, c‐kit ligand). The colony‐forming ability of HL60, K562, KG1 cells and eight fresh AML cell populations was assessed by a clonogenic assay in methylcellulose. In eight additional AML cases the number of S‐phase leukaemic cells induced by IL‐11 was determined by the bromodeoxyuridine (BRDU) incorporation assay after 3 d of liquid culture.IL‐11, as single cytokine, did not stimulate the colony formation of the three myeloid cell lines under serum‐containing and serum‐free conditions. In contrast, the proliferation of the leukaemic cells in response to IL‐3, GM‐CSF and SCF was enhanced by co‐incubation with IL‐11, and this effect was reversed in blocking experiments by the anti‐IL‐11 Moab. When tested on primary AML samples, IL‐11 alone showed little, if any, proliferative activity. However, it increased the IL‐3‐dependent blast colony formation in eight out of eight cases and GM‐CSF in seven cases. IL‐11 also augmented synergistically the number of CFU‐L stimulated by SCF in seven cases. A combination of three factors (IL‐11, SCF and IL‐3) yielded optimal colony formation. The BRDU studies showed the significant increase of AML cells in S‐phase when IL‐11 was combined with SCF, whereas the two CSF had no activity on their own. Positive interaction was also observed when IL‐11 was added to IL‐3 supplemented cultures in five out of eight cases tested. Reverse transcriptase‐polymerase chain reaction amplification (RT‐PCR) demonstrated the constitutive expression of IL‐11 mRNA in all the cell lines and 11/12 AML samples studied at diagnosis.These results indicate that IL‐11 is expressed in leukaemic myeloid cells and that their proliferation is regulated by the cytokine which acts as a synergistic factor.
Pharmacokinetic and pharmacodynamic studies of subcutaneously administered recombinant human interleukin‐3 following chemotherapy for non‐Hodgkin's lymphoma
Authors: Hovgaard D. J. , Mortensen B. T. , Nissen N. I. 
Published: March 2008

Summary. The pharmacokinetics and the pharmacodynamic profile of subcutaneously administered recombinant human non‐glycosylated interleukin‐3 (rhIL‐3) was studied in lymphoma patients after standard CHOP chemotherapy. 30 patients received 0.5, 1.0, 5.0, 7.5 and 10/ig/kg (six patients at each dose level) of rhIL‐3 for 14 d. Serum rhIL‐3 samples were obtained regularly during the treatment and serially over a 24 h period on the first (cycle day 2) and the last (cycle day 15) day of rhIL‐3 treatment for pharmacokinetic evaluation. Following s.c. injection on cycle day 2, the maximum rhIL‐3 serum concentration ranged from 289pg/ml (0‐5/ig/kg) to 4690pg/ml (10/xg/kg). Both the maximum serum concentration (R= 0.90, P< 0.0001) and the area under the serum concentration‐time curve (R= 0.95, P< 0.0001) were related to dose.The elimination half‐life T1/2β was 160 min for 0.5 μg/kg and 134 min for 10μg/kg, with no apparent dose relationship. The systemic clearance of 3.0–6.0ml/min/kg was comparable at all dose levels. No significant difference was noted between pharmacokinetic parameters on the first day of rhIL‐3 and the last day of treatment, and no accumulation of the drug was noted throughout the study. The pharmacokinetic parameters correlated poorly to the clinical response of the growth factor, where dose in μg/kg seemed to be the most important single factor.
Psychometric properties of the Mental Retardation Attitude Inventory‐Revised in Chinese college students
Authors: Hampton N. Z. , Xiao F. 
Published: March 2008

AbstractBackground  This study examines the psychometric properties of the Mental Retardation Attitude Inventory‐Revised (MRAI‐R; Antonak & Harth) in Chinese college students. The research questions included: (1) Is the MRAI‐R a reliable measure for Chinese college student? (2) Is the MRAI‐R related to familiarity with people with intellectual disabilities (PWID) and professional training? and (3) Does the four‐factor model of the MRAI‐R fit the Chinese college student data?Method  Five hundred and thirty‐four college students from China participated in the study. Descriptive, Pearson product‐moment correlation, Cronbach alpha reliability coefficient and factor analyses were used to examine the reliability and validity of the MRAI‐R in this Chinese college student sample.Results  The alpha coefficient reliability of the total scale of the MRAI‐R was 0.78. The alpha coefficient reliabilities for the integration–segregation (INSE) subscale, the social distance (SDIS) subscale, the private rights (PRRT) subscale and the subtle derogatory beliefs (SUDB) subscale were 0.50 (INSE), 0.78 (SDIS), 0.50 (PRRT) and 0.21 (SUDB) respectively. Correlation analyses indicated that familiarity with PWID and professional training had a weak correlation with attitudes towards PWID. A confirmatory factor analysis revealed that the standardized factor loadings and goodness‐of‐fit indices were inadequate (the chi‐square/degrees of freedom ratio = 3.24; the goodness‐of‐fit index = 0.85; the comparative fit index = 0.69; the RMSEA* = 0.07). A principal axis factoring analysis (PAF) with oblique rotation identified three factors with 25% of the variance accounted for the sample. However, the results of this PAF were factorial complex and not interpretable in that many items of the scale had double loadings on more than one factor.Conclusions  The factor structure of the MRAI‐R in this sample of Chinese college students did not replicate the structure found in American adults. Although the SDIS subscale of the MRAI‐R appeared to be a reliable instrument among the four subscales of the MRAI‐R, the reliabilities of the INSE, PRRT and SUDB subscales were low. Continuing investigations of the utility of the MRAI‐R in Chinese culture is needed. Attitude instruments based on Chinese culture may be developed.
Clarification of the memory artefact in the assessment of suggestibility
Authors: Willner P. 
Published: March 2008

AbstractAim  The Gudjonsson Suggestibility Scale (GSS) assesses suggestibility by asking respondents to recall a short story, followed by exposure to leading questions and pressure to change their responses. Suggestibility, as assessed by the GSS, appears to be elevated in people with intellectual disabilities (ID). This has been shown to reflect to some extent the fact that people with ID have poor recall of the story; however, there are discrepancies in this relationship. The aim of the present study was to investigate whether a closer match between memory and suggestibility would be found using a measure of recognition memory rather than free recall.Method  Three modifications to the procedure were presented to users of a learning disabilities day service. In all three experiments, a measure of forced‐choice recognition memory was built into the suggestibility test. In experiments 1 and 2, the GSS was presented using either divided presentation (splitting the story into two halves, with memory and suggestibility tests after each half) or multiple presentation (the story was presented three times before presentation of the memory and suggestibility tests). Participants were tested twice, once with the standard version of the test and once with one of the modified versions. In experiment 3, an alternative suggestibility scale (ASS3) was created, based on real events in a learning disabilities day service. The ASS3 was presented to one group of participants who had been present at the events, and a second group who attended a different day service, to whom the events were unfamiliar.Results  As observed previously, suggestibility was not closely related to free recall performance: recall was increased equally by all three manipulations, but they produced, respectively, no effect, a modest effect and a large effect on suggestibility. However, the effects on suggestibility were closely related to performance on the forced‐choice recognition memory task: divided presentation of the GSS2 had no effect on either of these measures; multiple presentation of the GSS2 produced a modest increase in recognition memory and a modest decrease in suggestibility; and replacing the GSS with the ASS3 produced a large increase in recognition memory and a large decrease in suggestibility.Implications  The results support earlier findings that the GSS is likely to overestimate how suggestible a person will be in relation to a personally significant event. This reflects poor recognition memory for the material being tested, rather than increased suggestibility per se. People with ID may in fact be relatively non‐suggestible for well‐remembered events, which would include personally significant events, particularly those witnessed recently.