bluuebunny/crossref_metadata_2025_split huggingface dataset:
Large‐cell variants of mantle cell lymphoma: cytologic characteristics and p53 anomalies may predict poor outcome
Authors: Zoldan Maria Cristina , Inghirami Giorgio , Masuda Yuichi , Vandekerckhove Filip , Raphael Bruce , Amorosi Edward , Hymes Kenneth , Frizzera Glauco 
Published: October 2003

Large‐cell variants are uncommon in mantle cell lymphoma (MCL). Here we describe the pathologic and clinical findings in five patients with large‐cell lymphoma related to MCL (L‐MCL), and compare them to a group of classic small‐cell MCL (s‐MCL) cases.Histologically, the MC origin of the large cells was evinced by their association with a small mantle cell component in the same tissue, or their distribution in a classic mantle zone pattern, or their development in a patient with previous s‐MCL. The large cells were either pleomorphic mantle cells (case 1) or transformed blast‐like cells (cases 2–5). The median nuclear diameter, median nuclear area and proliferation index of L‐MCLs and s‐MCLs, were statistically different. Immunophenotypic characterization of four specimens of L‐MCL and 10 of s‐MCLs with a large panel of antibodies showed the classic findings of MCL, i.e. the IgM+ D+/−, CD5+, CD10−, CD23− phenotype in all cases except two (one CD5− and one CD23+), and the association with a loose follicular dendritic cell network. Two of four L‐MCLs and 5/10 s‐MCLs demonstrated rearrangements of the bcl‐1 gene by Southern blot or by polymerase chain reaction (PCR); 2/4 L‐MCLs and 1/9 s‐MCLs had p53 mutations on single‐strand conformation polymorphism analysis; none of the 14 specimens showed rearrangement of bcl‐2 by PCR or bcl‐6 and c‐myc by Southern blot. All patients with ‘transformed’ histology (versus 37% of all others) died of lymphoma; their survival (15–18 months; median 17) was much shorter than that of all the others (28–117+ months; median 43) (P = 0.0035). All three patients with p53 anomalies, two of whom had tumours with transformed histology, died of their disease in a short time (15, 18 and 28 months). In contrast, the presence of bcl‐1 rearrangements did not have prognostic implications.This study documents the existence of large‐cell variants of MCL and the poor prognosis associated with the ‘transformed’ cytologic type and/or p53 abnormalities.
CD34 selections from myeloma peripheral blood cell autografts contain residual tumour cells due to impurity, not to CD34+ myeloma cells
Authors: Willems P. , Croockewit A. , Raymakers R. , Holdrinet R. , Van Der Bosch G. , Huys E. , Mensink E. 
Published: October 2003

Malignant cells in haemopoietic autografts can contribute to post‐transplant relapse. Engraftment of myeloma patients with CD34+ peripheral blood progenitors selected from total autografts reduces the number of tumour cells infused by 2.7–4.5 logs. Residual tumour cells detected in CD34+ selected cells may be due to selection impurity or the existence of malignant CD34+ progenitors. In three patients we evaluated the CD34 purity and tumour load of total autografts, CD34+ progenitors selected with immunomagnetic beads and highly purified CD34+ progenitors obtained in two rounds of selection (combining magnetic with flow cytometry activated cell sorting) to determine the cause of residual tumour cells in CD34 selections.Using allele‐specific oligonucleotides (ASO) complementary to the unique Ig heavy chain sequence (CDRIII region) of the malignant clone, semi‐quantitative ASO‐PCR was capable of detecting one malignant cell in 104–105 normal white blood cells. Selection of CD34+ cells from bone marrow (BM) with approximately 20% malignant plasma cells resulted in a 1.4 log reduction of tumour burden. Using two‐colour flow‐cytometry we observed CD34−, BB4+ malignant plasma cells contaminating this CD34 selection. Prior to sorting, peripheral blood cell autografts (PBCA) contained approximately 0.1% malignant cells. Selection of >99% pure CD34+ cells using immunomagnetic beads (Dynal) resulted in an approximate 2 log reduction of malignant cells, but residual tumour cells were still detectable. ASO‐PCR detected no malignant cells in >99.9% pure CD34+ peripheral blood progenitors obtained with two rounds of selection (combining magnetic with flow cytometry activated cell sorting). We conclude that CD34+ malignant cells are not detectable in myeloma PBCA and that residual tumour cells in CD34 selections are due to contaminating CD34‐negative cells.
A comparison of busulphan versus total body irradiation combined with cyclophosphamide as conditioning for autograft or allograft bone marrow transplantation in patients with acute leukaemia
Authors: Ringdén O. , Labopin M. , Tura S. , Arcese W. , Iriondo A. , Zittoun R. , Sierra J. , Gorin N. C. 
Published: October 2003

We retrospectively compared the outcome in patients in the EBMT database transplanted for acute leukaemia from January 1987 to January 1994 who received busulphan and cyclophosphamide (BU/CY) as a pretransplant regimen versus those who received cyclophosphamide and total‐body irradiation (CY/TBI). The patients were matched for type of transplant (autologous bone marrow transplantation (ABMT) versus allogeneic (BMT)), diagnosis (acute lymphoblastic leukaemia (ALL) or acute myeloid leukaemia (AML)), status (early (first complete remission, CR‐1) versus intermediate (second or later remission, first relapse)), age, FAB classification for AML, prevention of graft‐versus‐host disease and year of transplantation. In ABMT recipients (matched paired 530 × 2) with ALL CR‐1, AML CR‐1 and AML intermediate disease, transplant‐related mortalities (TRM), relapse incidence (RI) and leukaemia‐free survival (LFS) did not differ significantly in patients treated with BU/CY or CY/TBI. However, in ABMT recipients with ALL intermediate disease, the probability of relapse was 82 ± 5% (±95% confidence interval) in the BU/CY group compared to 62 ± 6% in the CY/TBI group (P = 0.002) and the 2‐year leukaemia‐free survival 14 ± 4% and 34 ± 6%, respectively (P = 0.002). In BMT recipients of bone marrow from HLA‐identical siblings (matched paired 391 × 2), the TRM, RI and LFS did not differ significantly between the two treatments in all groups. In particular, the 2‐year LFS in patients with AML CR‐1 was 64 ± 3% in those treated with BU/CY (n = 237) compared to 66 ± 3% in those given CY/TBI (n = 237). In all groups the findings were confirmed in a multivariate analysis of prognostic factors. Veno‐occlusive disease (VOD) of the liver (P < 0.05) and haemorrhagic cystitis (P < 0.001) was more common in the BU/CY group compared to the CY/TBI group for ABMT and BMT patients.In conclusion, BU/CY and CY/TBI as pretransplant regimens gave similar results in all situations, except ABMT for ALL intermediate stages with more than 2 years from diagnosis to transplantation, where a lower RI and a higher LFS were associated with CY/TBI.
A sensitive sandwich ELISA for measuring thrombopoietin in human serum: serum thrombopoietin levels in healthy volunteers and in patients with haemopoietic disorders
Authors: TAHARA TOMOYUKI , USUKI KENSUKE , SATO HIROAKI , OHASHI HIDEYA , MORITA HARUHIKO , TSUMURA HARUHIKO , MATSUMOTO ATSUSHI , MIYAZAKI HIROSHI , URABE AKIO , KATO TAKASHI 
Published: October 2003

A sensitive sandwich enzyme‐linked immunosorbent assay (ELISA) has been established to estimate serum thrombopoietin (TPO) concentrations in healthy volunteers and patients with haemopoietic disorders. The ELISA uses a mouse monoclonal antibody (Ab) as the capture Ab and a biotinylated rabbit polyclonal Ab as the detector. The ELISA was reproducible, highly sensitive and specific for human TPO. The coefficients of intra‐ and inter‐assay variation were from 3.0% to 4.9% and from 5.9% to 6.1%, respectively. The quantitative limit of the ELISA was 0.09 fmol/ml in serum. The quantitative limit was lower than the normal level. The dose–response curves of serum samples from healthy volunteers and patients with haemopoietic disorders were parallel to the standard curves. The ELISA did not cross‐react with a variety of blood components and cytokines to produce false‐positive results.The serum TPO concentrations from 29 normal males and 21 females were 0.79 ± 0.35 and 0.70 ± 0.26 fmol/ml, respectively. Serum TPO levels in patients with aplastic anaemia (AA), acute lymphocytic leukaemia (ALL) and essential thrombocythaemia (ET) were measured using the ELISA. The serum TPO levels in the patients with ET (n = 6, 2.80 ± 1.55 fmol/ml) were higher than the normal level. The patients with AA (n = 7, 18.53 ± 12.37 fmol/ml) and ALL (n = 5, 10.36 ± 5.57 fmol/ml) had significantly higher serum TPO levels than normal individuals. These results indicate that the ELISA specific to TPO should prove useful in measuring the TPO concentration in serum samples.
COLLECTION AND TRANSPLANTATION OF PERIPHERAL BLOOD PROGENITOR CELLS MOBILIzED BY G‐CSF ALONE IN CHILDREN WITH MALIGNANCIES
Authors: Diaz M. A. , Villa M. , Alegre A. , Lamana M. L. , De La Vega A. , Granda A. , Madero L. 
Published: October 2003

Results of collection and transplantation of peripheral blood progenitor cells (PBPC) mobilized by G‐CSF in 31 children with different malignancies were analysed. A total of 43 aphereses were performed, following administration of granulocyte colony‐stimulating factor (G‐CSF), using a continuous flow blood cell separator (Cobe Spectra) through a central venous catheter. For patients weighing ≤25 kg the extracorporeal line was primed with red blood cells. The mean blood flow rate was 33.2ml/min (range 12–56ml/min). The mean number of mononuclear cells (MNC), granulocyte‐macrophage colony‐forming units (CFU‐GM) and CD34+ cells collected were 7.22×108/kg body weight (b.w.), 15.9×104/kg and 5.44×106/kg respectively.The morbidity related to PBPC collection was low and the mean apheresis time was 302.7min (range 115–492). The volume of processed blood for apheresis (per kilogram body weight) ranged from 117 to 539.6 (mean 309.13ml/kg). 20 patients required only one apheresis to collect the minimum requirement of 5–7×108/kg of MNC.All patients subsequently underwent autografting with PBPC after myeloablative therapy. Days to achieve an absolute count of neutrophils (ANC) <0.5×109/l and a platelet count of 20×1092/l without platelet support were 9.5 and 18, respectively. The number of CD34+ cells infused correlated highly with engraftment kinetics. The extramedullary toxicity was low and manageable.
Parenteral iron increases serum erythropoietin concentration during the ‘early anaemia’ of 10–20‐day‐old mice
Authors: Bechensteen Anne Grete , Halvors en Sverre 
Published: October 2003

Parenteral iron abolishes the ‘early anaemia’ in all mammals tested and increases packed cell volume (PCV) and haemoglobin concentration (Hb) significantly above adult levels. In the present study we examined the effect of parenteral iron upon serum immunoreactive erythropoietin (siEpo) concentration in young mice (age 6–24 d) and in adult iron‐deficient mice.Young BALB/CJ mice, from 5 to 23 d of age, and adult (60–100 d old) mice, some of which were iron deficient due to a low iron diet from the time of weaning, were given iron subcutaneously (iron sorbitol, Fe+++, 1.2 mg iron/100 g body weight/injection). Iron was given as one single dose and the animals killed 20–24 h later. Control mice were similarly treated with saline.  In young mice, from the age 10 d to weaning at 20 d, the siEpo level, measured 20–24 h after a single subcutaneous dose of iron, was 5 times greater than that in control mice (P < 0.0001). In contrast, there was no change in siEpo 20–24 h after a single subcutaneous dose of iron in adult mice, whether iron‐deficient anaemic or normal.Thus, during the ‘early anaemia’ in young mice over 10 d old, iron increased siEpo levels, whereas it had no such effect in iron‐deficient and normal adult mice, This suggests that between ages 10 and 20 d, iron has additional effects in the regulation of erythropoiesis, which may not occur in adult or in 6‐d‐old mice.
Issues facing brothers of sexually abused children: implications for professional practice
Authors: Hill Andrew 
Published: October 2003

ABSTRACTThis paper draws on the author's experience of undertaking play therapy with the brothers of sexually abused children. It illustrates the range of difficulties that such boys may face and identifies implications for professional practice. Difficulties are understood as arising from the struggle to develop a coherent narrative about the abuse, often in the face of incomplete or contested information. The outcome is influenced by the nature of the child's attachment relationships with his non‐abusing parents or carers, his abused sibling and with the abuser himself. This struggle for a coherent narrative about the sexual abuse can have a significant impact on the development of a sense of masculine identity, particularly when the abuser is the boy's own father and/or the abused child is male. In the context of increasing professional awareness of the need to support siblings of sexually abused children it is argued that there should be a specific focus on gender and identity issues for boys.
Worries and problems of young carers: issues for mental health
Authors: Cree Viviene E. 
Published: October 2003

ABSTRACTThis paper reports on a research study which explored the worries and problems of young carers in Edinburgh. Sixty‐one young carers took part in the study, conducted between April and June 2002. Findings indicate that young carers identify significant worries and problems in relation to their well‐being, and that these come over and above any ‘normal’ adolescent difficulties. It is suggested that these findings may have important implications for young carers’ mental health, now and in the future, and contain important lessons for child and family social work in general.
Parenting fostered adolescents: skills and strategies
Authors: Lipscombe Jo , Farmer Elaine , Moyers Sue 
Published: October 2003

ABSTRACTThis paper discusses findings from a recently completed study of adolescent foster care, which included a detailed assessment of the parenting approaches and strategies used by the foster carers of adolescents in long‐term placements. Sixty‐eight foster carers were interviewed at two points in time. The first interview was conducted two months after the start of a new adolescent placement and the second after the placement had been continuing for a year, or at the point of disruption if this occurred earlier. The interview schedules were designed specifically for this study and were based upon well‐established techniques developed in other studies of parenting. They enabled the researchers to make summary ratings for each carer on established dimensions of parenting such as control and discipline, responsiveness and the level of engagement with the child. The researchers assessed how these strategies changed and developed in relation to the young person's behaviour and whether these approaches influenced either the likelihood of placement disruption or the quality of the placement for the child. This paper describes the parenting strategies used by the foster carers, highlighting the areas of parenting that significantly affected the placement outcomes and the corresponding implications for policy and practice.
Between a rock and a hard place: the role of relatives in protecting children from the effects of parental drug problems
Authors: Barnard Marina 
Published: October 2003

ABSTRACTUsing qualitative data gathered from 62 problem drug using parents in Glasgow, Scotland, this paper explores the role played by the extended family in protecting children from some of the negative effects of parental drug use. However, the data also indicated that the intervention of the extended family, whilst often critical, was not without its tensions and difficulties for parents, for the extended family and for the children too. What seemed to obtain in most cases was a complex and volatile mix of practical and emotional concerns over children's appropriate care and issues of responsibility and obligation to the child. These in turn were overlaid by expressions of anxiety, worry, anger and disappointment over both the parent's drug problem and its profound effect on the family. Strained family dynamics and a lack of a supportive welfare infrastructure can all compromise the ability of kin to provide a stable, nurturing environment for children over time. In a worst case scenario it can lead to a breakdown of these care arrangements, leaving these already vulnerable children exposed to further rupture, emotional damage and instability. If we are to avoid such outcomes it is crucial that we first identify and then work to rectify those factors that compromise the abilities of extended family carers to look after these children both in the short and the longer term.
Broadening constructions of family violence: mothers’ perspectives of aggression from their children
Authors: Jackson Debra 
Published: October 2003

ABSTRACTThis qualitative study used feminist insights to explore experiential aspects of the phenomenon of child‐to‐mother violence from the perspectives of six women survivors. Participants took part in conversational style audiotaped interviews lasting between two and four hours. Feminist analysis revealed that fear and violence had become a feature of mothering for these women. Three themes were identified: It was only a matter of time: feeling intimidated and under threat; He just punched me: physical violence from child to mother; and Other men in the house: violence directed to the mothers by friends and associates of their children. Currently the literature overwhelmingly constructs family violence as elder abuse, spousal/partner violence, or child abuse, and generally fails to acknowledge, or address, violence from children to parents. However, findings from this study suggest that the discourse about family violence needs to be broadened to include child‐to‐mother violence. Implications of this study for practice and research are discussed.
Differential activities, subcellular distribution and tissue expression patterns of three members of Slingshot family phosphatases that dephosphorylate cofilin
Authors: Ohta Yusaku , Kousaka Kazuyoshi , Nagata‐Ohashi Kyoko , Ohashi Kazumasa , Muramoto Aya , Shima Yasuyuki , Niwa Ryusuke , Uemura Tadashi , Mizuno Kensaku 
Published: October 2003

AbstractBackground:  Cofilin, a key regulator of actin filament dynamics, is inactivated by phosphorylation at Ser‐3 by LIM‐kinases and is reactivated by dephosphorylation by a family of protein phosphatases, termed Slingshot (SSH).Results:  We have identified two novel isoforms of SSHs, termed SSH‐2L and SSH‐3L and characterized them in comparison with SSH‐1L that was previously reported. SSH‐1L and SSH‐2L, but not SSH‐3L, tightly bound to and co‐localized with actin filaments. When expressed in cultured cells, SSH‐1L, SSH‐2L and SSH‐3L decreased the level of Ser‐3‐phosphorylated cofilin (P‐cofilin) in cells and suppressed LIM‐kinase‐induced actin reorganization, although SSH‐3L was less effective than SSH‐1L and SSH‐2L. In cell‐free assays, SSH‐1L and SSH‐2L efficiently dephosphorylated P‐cofilin, whereas SSH‐3L did do so only weakly. Using deleted mutants of SSH‐1L and SSH‐2L, we found that the N‐terminal and C‐terminal extracatalytic regions are critical for cofilin‐phosphatase and F‐actin‐binding activities, respectively. In situ hybridization analyses revealed characteristic patterns of expression of each of the mouse Ssh genes in both neuronal and non‐neuronal tissues; in particular, expression of Ssh‐3 in epithelial tissues is evident.Conclusion:  SSH‐1L, SSH‐2L and SSH‐3L have the potential to dephosphorylate P‐cofilin, but subcellular distribution, F‐actin‐binding activity, specific phosphatase activity and expression patterns significantly differ, which suggests that they have related but distinct functions in various cellular and developmental events.
Negative regulation of Lyn protein‐tyrosine kinase by c‐Cbl ubiquitin‐protein ligase in FcɛRI‐mediated mast cell activation
Authors: Kyo Shinkou , Sada Kiyonao , Qu Xiujuan , Maeno Koichiro , Miah S. M. Shahjahan , Kawauchi‐Kamata Keiko , Yamamura Hirohei 
Published: October 2003

AbstractBackground: Recent studies have demonstrated that c‐Cbl functions as a ubiquitin‐protein ligase toward immune receptors and non‐receptor protein‐tyrosine kinase Syk by facilitating their ubiquitination and subsequent targeting to proteasomes. However, it was not clear whether Src family kinase Lyn is regulated by the Cbl family of ubiquitin‐protein ligases.Results:  Aggregation of the high affinity IgE receptor (FcɛRI) induces the rapid ubiquitination of Lyn in rat basophilic leukaemia RBL‐2H3 cells. Treatment of cells with a proteasome inhibitor enhances the ubiquitination of Lyn. Stimulation of FcɛRI results in the association of Lyn with c‐Cbl and Cbl‐b, both of which then become tyrosine phosphorylated. Co‐transfection study shows that both c‐Cbl and Cbl‐b could induce the ubiquitination of activated Lyn in COS cells. Furthermore, over‐expression of membrane‐anchored form of c‐Cbl inhibits the FcɛRI‐mediated degranulation and cytokine gene production in RBL‐2H3 cells by the down‐regulation of the kinase activity of Lyn through the enhanced ubiquitination.Conclusions:  These results demonstrate that Lyn is down‐regulated by c‐Cbl‐mediated ubiquitination and subsequent degradation in proteasome after FcɛRI stimulation in mast cells. Targeting of c‐Cbl in the lipid raft results in the inhibition of FcɛRI‐mediated mast cell activation.
On multiple solutions of the atmosphere–vegetation system in present‐day climate
Authors: Claussen Martin 
Published: October 2003

AbstractAn asynchronously coupled global atmosphere–biome model is used to assess the stability of the atmosphere–vegetation system under present‐day conditions of solar irradiation and sea‐surface temperatures. When initialized with different land‐surface conditions (1, the continents, except for regions of inland ice, completely covered with forest; 2, with grassland; 3, with (dark) desert; and 4, with (bright) sand desert), the atmosphere–biome model finds two equilibrium solutions: the first solution yields the present‐day distribution of subtropical deserts, the second reveals a moister climate in North Africa and Central East Asia and thereby a northward shift of vegetation particularly in the south‐western Sahara. The first solution is obtained with initial condition 4, and the second with 1, 2, 3. When comparing these results with an earlier study of biogeophysical feedback in the African and Asian monsoon area, it can be concluded that North Africa is probably the region on Earth which is most sensitive considering bifurcations of the atmosphere–vegetation system at the global scale.