bluuebunny/crossref_metadata_2025_split huggingface dataset:
The mechanism of red cell (dis)aggregation investigated by means of direct cell manipulation using multiple optical trapping
Authors: BRONKHORST P. J. H. , GRIMBERGEN J. , BRAKENHOFF G. J. , HEETHAAR R. M. , SIXMA J. J. 
Published: December 2004

We used multiple optical trapping to study the mechanism of red cell (dis)aggregation. Two sets of optical ‘tweezers’ were used to bring two red blood cells together to form a two‐cell aggregate and then to pull them apart, to study the interaction between the cells.We found that cross‐bridging occurred in normal reversible aggregation as we observed binding and the occurrence of small tethers between opposite cell membranes. Furthermore, the cells could only be parted by sliding them side by side with a maximum velocity in the order of μm/s indicating accumulation of the cross‐bridges.
Additional chromosome abnormalities confer worse prognosis in acute promyelocytic leukaemia
Authors: HIORNS LYNNE R. , SWANSBURY G. JOHN , MEHTA JAYESH , MIN TOON , DAINTON MELISSA G. , TRELEAVEN JENNIE , POWLES RAYMOND L. , CATOVSKY DANIEL 
Published: December 2004

Acute promyelocytic leukaemia (APL) has been associated with a favourable prognosis in many studies of acute myeloid leukaemia. A series of 54 patients treated at the Royal Marsden Hospital between 1979 and 1996, with APL and the t(15;17) chromosome translocation at pres‐entation, was examined for the effect of additional chromosome abnormalities in their presentation karyotype on survival.The patients were aged between 2 and 62 years with a median age of 31 years. There were approximately equal numbers of males and females. Presentation white cell count ranged from 0.7 to 156 × 109/l with a median of 1.0 × 109/l. 39% of patients (21/54) had additional chromosome abnormalities at presentation. Statistical analyses were performed for factors thought to influence survival such as age, sex, white cell count, and number of courses of chemotherapy required to enter remission. These showed that the presence of additional chromosome abnormalities has an adverse effect on prognosis, independent of other prognostic indicators, reducing it to the level of patients with AML from less‐favourable cytogenetic subgroups. These data indicate that additional therapeutic strategies may be required in patients with APL who demonstrate cytogenetic aberrations over and above the t(15;17) at presentation. The biological basis for the more aggressive nature of these cases remains to be determined.
Multigenetic lesions in infant acute leukaemias: correlations with ALL‐1 gene status
Authors: CIMINO GIUSEPPE , LANZA CARLO , ELIA LOREDANA , LO COCO FRANCESCO , GAIDANO GIANLUCA , BIONDI ANDREA , PASTORE CRISTINA , SERRA ANNA , CANAANI ELI , CRPCE CARLO MARIA , MAMDEO FRAMCP , SAGLIO GIUSEPPE 
Published: December 2004

In this study we investigated the presence of structural lesions in the ALL‐1, p53 and p16 (cyclin‐dependent kinase 4 inhibitor) genes in leukaemic cells obtained from 22 patients with infant acute leukaemia (aged <18 months). Of these, 18 cases were classified as acute lymphoblastic leukaemia (ALL) and four as acute myeloid leukaemia (AML). Tumour DNAs were analysed by a combination of Southern blot, polymerase chain reaction (PCR), single‐strand conformation polymorphism (SSCP), and direct sequence analyses.The results showed ALL‐1 gene rearrangements in 15/22 (68%) cases, p53 gene mutations in 5/22 (26%), and a homozygous deletion of p16 in a single T‐ALL case. p53 and p16 alterations were all found in the group of patients with ALL‐1 gene rearrangements. p53 mutations were more often associated with a myeloid phenotype (3/5).In summary, multiple molecular alterations were found in 6/15 (40%) infant acute leukaemias with ALL‐1 rearrangements. As to the clinical course, patients with additional lesions had similar clinical outcome with respect to patients with ALL‐1 gene rearrangement as the sole genetic aberration. This may support the hypothesis that ALL‐1 alterations are genetic events per se sufficient to confer a fully malignant phenotype to the leukaemic clone.
N‐linked sialyated sugar receptors support haematopoietic cell‐osteoblast adhesions
Authors: Crean S. M. , Meneski J. P. , Hullinger T. G. , Reilly M. J. , DeBoever E. H. , Taichman R. S. 
Published: December 2004

SummaryHaematopoietic progenitor cells proliferate and develop predominantly when they adhere to bone marrow stromal cells such as osteoblasts. Therefore, changes in adhesion may be a common mechanism by which stem cells survive, mature and properly traffic between the bone marrow and the circulation. To characterize these adhesion molecules, we reduced the bone marrow cavity to a simple adhesion assay between KG1a (a CD34+ haematopoietic cell line) and osteosarcoma monolayers (MG‐63 or SaOS‐2). The data demonstrated that adhesion was mediated by cell‐to‐cell rather than cell‐to‐matrix contact, was sensitive to trypsin, calcium chelators and glycosylation inhibitors. Selective pretreatment attributed the constitutive binding to N‐linked glycans on KG1a. When carboprocessing was inhibited later at the high mannose intermediate (via deoxymannojirimycin), adhesion was retained. Surprisingly, binding of KG1a to SaOS‐2 increased past constitutive levels as doses of tunicamycin or deoxymannojirimycin dropped. Selective pretreatment suggested that this ‘inducible’ binding resides with molecule(s) on SaOS‐2. If the terminal sialic acid was digested (via neuraminidase), this induced response was duplicated. These data, verified in primary cells, suggest that the initial tethering between blood and bone cells in this model is probably due to heavily glycosylated, rapidly processed protein(s) on both cell types.
Retroviral transduction of acute myeloid leukaemia‐derived dendritic cells with OX40 ligand augments their antigen presenting activity
Authors: Yanagita Soshi , Hori Toshiyuki , Matsubara Yasushi , Ishikawa Takayuki , Uchiyama Takashi 
Published: December 2004

SummaryRecent studies have shown that human myeloid leukaemia cells can differentiate into dendritic cell (DC)‐like cells (leukaemia‐DCs) when cultured with a combination of cytokines. In the present study, we examined whether the transduction of leukaemia‐DCs with OX40 ligand (OX40L), a member of the tumour necrosis factor (TNF) family, resulted in augmentation of their antigen presenting activity. Bicistronic retroviral vectors expressing both human OX40L and enhanced green fluorescent protein (EGFP) or EGFP alone were generated and used for transduction. Fresh leukaemic cells from five patients with acute myeloid leukaemia (AML) were isolated and retrovirally transduced with OX40L during the culture with a combination of cytokines from stem cell factor, fms‐like tyrosine kinase (Flt)‐3 ligand, granulocyte‐macrophage colony stimulating factor (GM‐CSF), interleukin‐4 (IL‐4) and TNF‐α. After 7 d, the majority of cells showed DC‐like morphology, and expressed higher levels of CD80, CD86 and HLA‐DR than fresh leukaemic cells. The transduction efficiency was 8·5–27·2%. Leukaemia‐DCs transduced with OX40L elicited higher proliferative response of allogeneic CD4+ T cells than fresh leukaemic cells, non‐transduced, or mock‐transduced leukaemia‐DCs. Co‐culture of allogeneic CD4+ T cells with OX40L‐transduced leukaemia‐DCs was superior in the generation of interferon (IFN)‐γ producing CD4+ T cells and in production of IFN‐γ. Furthermore, OX40L‐transduced leukaemia‐DCs could elicit significant proliferative response of human leucocyte antigen‐matched T cells from the donor in allogeneic stem cell transplantation. These results indicate that retroviral transduction of leukaemia‐DCs with OX40L augments their antigen presenting cell activity and thus renders them more suitable for tumour vaccines or ex vivo stimulation of leukaemia‐specific T cells.
The use of a national transplant registry to benchmark transplant outcome for patients undergoing autologous and allogeneic stem cell transplantation in the United Kingdom and Ireland
Authors: Russell N. H. , Szydlo R. , McCann S. , Potter M. N. , Craddock C. , Towlson K. , Apperley J. F. ,   British Society for Blood and Marrow Transplantation
Published: December 2004

SummaryAs part of its clinical governance programme the British Society for Blood and Marrow Transplantation (BSBMT) undertook an analysis of transplant outcome for adults undergoing human leucocyte antigen – identical sibling allogeneic transplantation for chronic myeloid leukaemia (CML) in first chronic phase (CP1) or autologous transplantation for Hodgkin's disease (HD). The study aimed to compare transplant‐related mortality (TRM) and survival for patients reported to the BSBMT with patients transplanted in the rest of Europe, reported to the European Group for Blood and Marrow Transplantation (EBMT). The outcomes for 104 allogeneic transplants for CML in 24 UK/Irish centres were compared with 775 allografts in 145 other European centres. For HD, 241 autografts from 38 UK/Irish centres were compared with 1145 transplants in 239 other European centres. For both diseases, the cohorts were broadly matched with the exception of CML, where 85% of patients were transplanted <1 year from diagnosis in the UK/Ireland compared with 68% in the EBMT (P = 0·001). Cox regression analysis was undertaken using known delineated variables affecting transplant outcome in addition to the registry of origin. The adjusted survival curves for CML showed no significant differences between the two groups, with 3‐year survival probabilities of 70·2% and 67·1% for the EBMT and BSBMT cohorts respectively. Likewise, the analysis for HD showed overlapping survival curves, with 3‐year survival probabilities of 71·8% (EBMT) and 70·8% (BSBMT). TRM was not statistically different in either disease. This study demonstrates the potential for using national registries to benchmark transplant outcome against the EBMT registry.
High plasma levels of factor VIII and risk of recurrence of venous thromboembolism
Authors: Cristina Legnani , Benilde Cosmi , Michela Cini , Mirella Frascaro , Giuliana Guazzaloca , Gualtiero Palareti 
Published: December 2004

SummaryThe aim of this study was to evaluate the relationship between factor VIII (FVIII) levels, measured by chromogenic and clotting assays, and risk of venous thromboembolism (VTE) recurrence. A total of 564 patients underwent clinical follow‐up after oral anticoagulant withdrawal (total follow‐up = 924·4 years). Recurrent VTE developed in 39 of 309 (12·6%) patients with a first idiopathic VTE and in 14 of 255 (5·5%) patients whose first event was secondary. In patients with a first idiopathic VTE, the risk of recurrence was more than fivefold higher in patients with FVIII levels exceeding the 90th percentile [chromogenic FVIII: relative risk (RR) 5·43 (95% CI 1·76–16·8); clotting FVIII: RR 6·21 (95% CI 1·57–24·5)] after adjustment for all possible confounding variables. In patients with a first secondary VTE, the risk of recurrence was slightly higher in patients with high FVIII levels [chromogenic FVIII: RR 2·62 (95% CI 0·34–19·9); clotting FVIII: RR 1·74 (95% CI 0·25–12·1)], but, given the low number of recurrences, the 95% CI were very large. In conclusion, this study shows that high FVIII levels are associated with increased risk of VTE recurrence in patients with a first idiopathic VTE. Although the measurement of FVIII levels by a specific chromogenic assay might, in principle, be preferred to avoid the risk of aspecific clotting effects, no significant differences in results obtained by chromogenic or clotting methods were found.
Dialysis of saliva improves accuracy of saliva lithium determinations
Authors: El‐Mallakh Rif S , Linder Mark , Valdes Roland , Looney Stephen 
Published: December 2004

Background:  Saliva lithium (Li) determinations have been explored as a potential alternative to plasma levels. Unfortunately, this method has been shown to be unreliable. Saliva has two major components: the aqueous and the mucopolysaccharide portions.Methods:  Since Li is likely to distribute only in the aqueous fraction, we dialyzed the saliva through a 3000 Da filter to isolate the aqueous component and determine the Li level in it.Results:  Lithium levels in the dialyzed saliva agreed more closely with plasma levels (Spearman's rho = 0.901, p < 0.001) than did whole saliva (Spearman's rho = 0.775, p = 0.012).Conclusion:  Dialysis of saliva may contribute to more accurate saliva Li levels.
Admission rates of bipolar depressed patients increase during spring/summer and correlate with maximal environmental temperature
Authors: Shapira Avraham , Shiloh Roni , Potchter Oded , Hermesh Haggai , Popper Miriam , Weizman Abraham 
Published: December 2004

Objective:  We intended to identify a relationship, if exists, between various climatic factors and the admission rates of bipolar affective disorder depressed patients (BPD) or major depressive disorder patients (unipolar) (UPD) to psychiatric hospitals, as well as potential seasonal variability in hospitalization rates of this population.Methods:  Data on admissions of ICD‐9 BPD and UPD patients to Tel Aviv's seven public psychiatric hospitals during 11 consecutive years were collected along with concomitant meteorological informationResults:  Admissions of 4117 patients with BPD and 1036 with UPD who fulfilled our specific inclusion criteria were recorded. Bipolar depressed, but not UPD, patients exhibited significant seasonal variation (higher spring and summer versus winter mean monthly admission rates), and the admission rates of patients with BPD, but not UPD, correlated significantly with mean maximal monthly environmental temperatureConclusions:  Increased environmental temperature may be a risk factor for evolvement of major depressive episode in patients with bipolar disorder with psychiatric co‐morbidity, at least in cases that necessitate hospitalization and at the examined geographic/climatic region of Israel. Further large‐scale studies with bipolar depressed patients with and without co‐morbid disorders are needed to substantiate our findings and to determine the role of seasonal and climatic influence on this population, as well as its relationship to the pathophysiology of bipolar disorder.
Short‐term fluoxetine monotherapy for bipolar type II or bipolar NOS major depression – low manic switch rate
Authors: Amsterdam Jay D , Shults Justine , Brunswick David J , Hundert Miriam 
Published: December 2004

Objectives:  Current guidelines for the initial treatment of bipolar type II (BP II) major depressive episode (MDE) recommend using either a mood stabilizer alone or a combination of a mood stabilizer plus a selective serotonin re‐uptake inhibitor (SSRI). This recommendation is the result of concern over antidepressant‐induced manic switch episodes. However, recent evidence suggests that the manic switch rate may be low in BP II MDE during SSRI therapy.Methods:  As part of a randomized, double‐blind, placebo‐controlled relapse‐prevention study of fluoxetine monotherapy in BP II MDE, 37 patients received open‐label fluoxetine 20 mg every day for up to 8 weeks. Outcome measures included the Hamilton Depression Rating (HAM‐D 17) rating and the Young Mania Rating (YMR) scale.Results:  Eleven of 23 patients (48%) who completed 8 weeks of fluoxetine treatment showed a HAM‐D 17 reduction of ≥50%, while 14 (38%) of all treated patients had ≥50% reduction in baseline HAM‐D 17 score. Using a conservative YMR score of ≥8 to identify hypomanic symptoms, the frequency of patients with YMR score ≥8 during fluoxetine did not differ from that seen during the screen and baseline period. Only three patients (7.3%) had symptoms suggestive of hypomania, and only one patient stopped treatment because of a rapid mood swing into depression.Limitations:  Fluoxetine was given at a fixed dose of 20 mg everyday. Fluoxetine was prescribed in an open‐label manner, and the sample size was limited.Conclusions:  These observations support the findings of a low manic switch rate during SSRI monotherapy of BP II MDE, and suggest that fluoxetine monotherapy may be a safe and effective initial treatment of BP II MDE.
A review of antidepressant‐induced hypomania in major depression: suggestions for DSM‐V
Authors: Chun Benjamin JDH , Dunner David L 
Published: December 2004

Objectives:  To determine if the classification of ‘antidepressant‐induced hypomania’ in DSM‐IV is supported by available data.Methods:  We reviewed the available scientific literature to examine the incidence of mania and hypomania in non‐bipolar patients who were treated with antidepressants.Results:  Eighty‐nine per cent of studies of antidepressants in major depressive disorder patients reported no cases of treatment‐induced hypomania. No instances of treatment‐induced hypomania were reported in three large studies of patients with chronic forms of depression.Conclusions:  The rate of antidepressant‐induced hypomania in major depressive disorder is within the rate of misdiagnosis of bipolar depression as unipolar. Depressed patients who experience antidepressant‐associated hypomania are truly bipolar.
Using technology to improve longitudinal studies: self‐reporting with ChronoRecord in bipolar disorder
Authors: Bauer Michael , Grof Paul , Gyulai Laszlo , Rasgon Natalie , Glenn Tasha , Whybrow Peter C 
Published: December 2004

Objectives: Longitudinal studies are an optimal approach to investigating the highly variable course and outcome associated with bipolar disorder, but are expensive and often have missing data. This study validates patient self‐reported mood ratings using a home computer‐based system (ChronoRecord) with clinician mood ratings on the Hamilton Depression Rating scale (HAMD) and Young Mania Rating scale (YMRS), and investigates the patient acceptance of the technology.Methods: After brief training, outpatients with bipolar disorder were given the software version of an established paper based self‐reporting form (ChronoSheet) to install on a home computer. Every day for 3 months, patients entered mood, medications, sleep, life events, and menstrual data. Weight was entered weekly.Results: Eighty of 96 (83%) patients returned 8662 days of data. The mean days of data returned was 114.7 ± 32.3 SD The mean percentage of days missing for mood data was 6.1% ± 9.3 SD, equivalent to missing 7.3 day of the 114.7 days. Self‐reported ratings were strongly correlated with clinician HAMD ratings (−0.683, p < 0.001).Conclusions: This study demonstrates concurrent validity between ChronoRecord and HAMD. Patients with bipolar disorder showed high acceptance of a computer‐based system for self‐reporting of daily data. Automation of data collection can reduce missing data and eliminate errors associated with data entry. This technology also enables on‐going feedback for both patient and researcher during a long‐term study.
Pharmacotherapy of bipolar II disorder: a critical review of current evidence
Authors: Hadjipavlou George , Mok Hiram , Yatham Lakshmi N 
Published: December 2004

Objectives:  There is much controversy surrounding the diagnosis and treatment of patients with bipolar II disorder (BP II). To address the growing need to find effective treatment strategies for patients with BP II, this article identifies and summarizes available published evidence specific to the pharmacotherapy of BP II.Methods:  Using the keywords, ‘bipolar disorder’, ‘type II’ or ‘type 2’, ‘bipolar II’, ‘hypomania’, and ‘bipolar spectrum’, a search of the databases Medline (via PubMed), the Cochrane Central Register of Controlled Trials (via Ovid), and PsychInfo was conducted for the period January 1994 to January 2003. Articles deemed directly relevant to the treatment of BP II were selected. Studies that included both BP I and II patients were excluded if results for BP II patients were not analyzed and reported separately.Results:  Fourteen articles were selected for the review period. There are no double blind, randomized controlled trials (RCT) involving only BP II patients. Most studies investigating the pharmacotherapy of BP II are methodologically limited, having observational or retrospective designs and small samples. For long‐term treatment, lamotrigine has the strongest quality of evidence (double blind RCT), while lithium is the best studied. With regard to short‐term treatment, there is some limited support for the use of risperidone in hypomania, and for divalproex, fluoxetine and venlafaxine in treating depression.Conclusions:  There is a paucity of sound evidence to help guide clinicians treating BP II patients. Decisions about pharmacotherapy should be made on a case‐by‐case basis; overall, broad recommendations that are based on available evidence cannot be adequately made. More quality research is needed to delineate effective treatment strategies.
Lithium prevents colchicine‐induced apoptosis in rat cerebellar granule neurons
Authors: Jordà EG , Verdaguer E , Morano A , Jiménez A , Canudas AM , Camins A , Pallàs M 
Published: December 2004

Objectives:  Here we evaluated the neuroprotective effects of two well‐known mood stabilizers, lithium and valproic acid (VPA), against colchicine neurotoxicity in cerebellar granule cells (CGNs).Methods:  The CGNs were differentiated for 7 days, pretreated with lithium or VPA for 24 h and after colchicine 1 μM was added. Cellular damage was assessed with 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl tetrazolium (MTT) method and apoptosis in CGNs was characterized by chromatin condensation and DNA fragmentation.Results:  Incubation with lithium (1–5 mM) attenuated this apoptosis markedly, in a dose–dependent way however, the addition of VPA (0.5–2 mM) did not protect CGNs. Colchicine‐induced apoptosis is mediated through the activation of caspase‐3. An increase in caspase‐3 activity was detected within 18 h and was blocked in presence of lithium 5 mM.Conclusions:  Our data indicate that lithium treatment is selectively neuroprotective; however, in our experimental conditions VPA did not protect CGNs from apoptosis induced by colchicine. Our results support the hypothesis that distinct pathways mediate the neuroprotective effects of lithium and VPA.
A prospective, longitudinal study of percentage of time spent ill in patients with bipolar I or bipolar II disorders
Authors: Joffe Russell T , MacQueen Glenda M , Marriott Michael , Trevor Young L 
Published: December 2004

Background:  There is a recent appreciation that patients with bipolar disorder spend a substantial period of time with minor or subsyndromal mood symptoms both manic and depressive. This study examined time spent in minor and subsyndromal mood states as well as with mania and depression in a cohort of well characterized bipolar I and II patients who were followed prospectively for an average of three years.Method:  Detailed life‐charting data were obtained from 138 patients with bipolar disorder. Mood states were characterized as euthymic, subsyndromal, minor or major affective episodes based on rigorously defined criteria. The amount of time spent in these mood states during follow‐up was examined.Results:  Patients in the total sample and within each bipolar subtype spent approximately half of their time euthymic. The remainder of the time was spent in varying severity of mood states. However, the majority of time was spent with minor and subsyndromal symptoms, both manic and depressive. Bipolar I patients differ from bipolar II in that significantly more time was spent with subsyndromal, minor and manic symptoms. There was no difference in time spent with depressive symptoms between the two groups.Conclusions:  Patients with bipolar disorder spend a substantial proportion of time with depressive or manic symptoms with the preponderance being minor or subsyndromal. Awareness of subthreshold symptoms in bipolar disorders and treatment of such symptoms may be improved by establishing guidelines that specifically outline appropriate strategies for reducing the duration of subsyndromal symptoms in bipolar disorder.