bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cdk‐inhibitors and exit from quiescence in primitive haematopoietic cell subsets
Authors: Steinman Richard , Yaroslavskiy Beatrice , Goff Julie P. , Alber Sean M. , Watkins Simon C. 
Published: January 2004

SummaryProlonged quiescence of haematopoietic stem cells has been proposed to support durable haematopoiesis through clonal succession. Genetic experiments in mice have implicated the cyclin‐dependent kinase inhibitor (cdki) p21Waf1 in sustaining stem cell quiescence, and the cdki p27Kip1 in inhibiting the expansion of more mature progenitor cells. The expression of these inhibitory proteins in human haematopoietic stem cell candidates has not hitherto been studied. We describe a rare subpopulation (3 × 10−7 umbilical cord mononuclear cells) of lineage‐negative cells that exhibited sustained resistance over months to cytokine‐induced cycling, and characterized the expression of p21Waf1 and p27Kip1 proteins in these cells. Whereas p27Kip1 was uniformly expressed in these cells, the expression of p21Waf1 in this population and in lineage‐negative CD34+ cells was variable. For this rare subset of cells exhibiting prolonged quiescence, p21Waf1 may be dispensable and p27Kip1 necessary for growth arrest.
Reactive oxygen species and phosphatidylserine externalization in murine sickle red cells
Authors: Banerjee Tinku , Kuypers Frans A. 
Published: January 2004

SummaryDue to their role in oxygen transport and the presence of redox active haemoglobin molecules, red blood cells (RBC) generate relatively high levels of reactive oxygen species (ROS). To counteract the potential deleterious effects of ROS, RBCs have a well‐integrated network of anti‐oxidant mechanisms to combat this oxidative stress. ROS formation is increased in sickle‐cell disease (SCD) and our studies in a murine SCD model showed a significant increase in the generation of ROS when compared with normal mice. Our data also indicated that murine sickle RBCs exhibit a significantly increased ATP catabolism, partly due to the increased activity of glucose‐6‐phosphate dehydrogenase and glutathione reductase to regenerate intracellular glutathione (GSH) levels to neutralize the adverse milieu of oxidative stress. Higher ATP consumption by the murine sickle RBCs, together with the increased ROS formation and impairment of the aminophospholipid translocase or flipase may underlie the exposure of phosphatidylserine on the surface of these cells.
CD27‐triggering on primary plasma cell leukaemia cells has anti‐apoptotic effects involving mitogen activated protein kinases
Authors: Guikema Jeroen E. J. , Vellenga Edo , Abdulahad Wayel H. , Hovenga Sjoerd , Bos Nicolaas A. 
Published: January 2004

SummaryPrimary plasma cell leukaemia (PCL) is a rare plasma cell malignancy, which is related to multiple myeloma (MM) and is characterized by a poor prognosis. In a previous study we demonstrated that PCL plasma cells display a high expression of CD27, in contrast to MM plasma cells. The present study was set out to assess the functional properties of CD27 expressed on PCL plasma cells by triggering with its ligand CD70. Using CD27‐expressing purified plasma cells from a PCL patient we demonstrated that CD27‐triggering modestly inhibited spontaneous and dexamethasone‐induced apoptosis. In vitro stimulation and Western blotting showed that activation of p38 and extracellular‐regulated kinase 1/2 (ERK1/2) mitogen‐activated protein kinases (MAPK) was associated with CD27‐mediated signal transduction. Specific inhibition of p38 and ERK1/2 MAPK abolished the anti‐apoptotic effects of CD27‐triggering. Interestingly, simultaneous inhibition of p38 and ERK1/2 strongly sensitized PCL cells for dexamethasone‐induced apoptosis. Finally, in dexamethasone‐treated PCL cells, CD27‐triggering was associated with persistent DNA‐binding activity of activator protein 1 (AP‐1) but not of nuclear factor‐κB. These findings suggest that, in primary PCL, specific anti‐apoptotic pathways exist that might provide novel therapeutic targets.
Dietary vitamin K influences intra‐individual variability in anticoagulant response to warfarin
Authors: Khan T. , Wynne H. , Wood P. , Torrance A. , Hankey C. , Avery P. , Kesteven P. , Kamali F. 
Published: January 2004

SummaryThe relationship between dietary intake of vitamin K, fat, plasma vitamin K concentrations and anticoagulation response to warfarin within individuals, as well as the contribution of dietary vitamin K to differences in warfarin dose requirements between individuals were investigated in 53 patients on warfarin therapy who had stably controlled anticoagulation. Each patient completed a dietary record of all foods consumed on a daily basis for 4 weeks. Each week a blood sample was taken for measurement of the international normalized ratio (INR), plasma vitamin K, triglycerides and warfarin enantiomer concentrations. The patients’ genotype for CYP2C9 was also determined. Regression analysis of the data showed that, for each increase of 100 μg in the daily dietary intake of vitamin K averaged over 4 d, the INR was reduced by 0·2. There was no correlation between warfarin daily dose and average daily dietary vitamin K intake when calculated over 28 d. The regression model for warfarin dose showed that, while dietary vitamin K had no effect, CYP2C9 genotype (P = 2%) and age (P < 1%) significantly contributed to inter‐patient variability in warfarin dose requirements. A consistent intake of vitamin K could reduce intrapatient variability in anticoagulation response and thus improve the safety of warfarin therapy.
Signalling molecules and cytokine production in T cells of multiple myeloma‐increased abnormalities with advancing stage
Authors: Mozaffari Fariba , Hansson Lotta , Kiaii Shahryar , Ju Xiuli , Rossmann Eva D. , Rabbani Hodjattallah , Mellstedt Håkan , Österborg Anders 
Published: January 2004

SummaryT‐cell immune dysfunction in patients with malignant tumours has been attributed to the altered expression of components of the T‐cell receptor (TCR)/CD3 complex and their associated intracellular protein tyrosine kinases. In this study, four‐colour flow cytometry was applied to study the surface bound molecules TCRαβ, CD28, CD152 and CD154 involved in T‐cell signalling and the signal transduction molecules CD3ζ, p56lck, p59fyn, ZAP‐70 and phosphatidyl‐inositol‐3 kinase (PI3‐k) as well as the intracellular cytokines interferon‐γ (IFN‐γ), interleukin (IL)‐4 and IL‐2 as a functional read‐out of non‐stimulated and superantigen (staphylococcus enterotoxin B)‐stimulated blood T cells of multiple myeloma (MM) patients at different stages of the disease. Multiple abnormalities were demonstrated in the CD4 and CD8 populations, both under non‐stimulated and superantigen‐stimulated conditions. There was a marked reduction, particular in advanced stage MM, in the proportion of CD4 and CD8 cells expressing CD28, CD152, CD3ζ, p56lck, ZAP‐70 and PI3‐k. The level of intracellular T‐cell cytokines (IFN‐γ, IL‐2 and IL‐4) was normal or increased in non‐stimulated cells but activation‐induced cytokine production was impaired. These results illustrated profound and multiple T‐cell signalling defects, from the surface and down‐stream, consistent with involvement of a master T‐cell function, especially in advanced stage MM. These data should be taken into consideration when developing immune‐based therapeutic approaches and when applying new emerging technologies that aim to restore T‐cell functions.
Reliable detection of clonal IgH/Bcl2 MBR rearrangement in follicular lymphoma: methodology and clinical significance
Authors: Iqbal Sameena , Jenner Michael J. R. , Summers Karin E. , Davies Andrew J. , Matthews Janet , Norton Andrew J. , Calaminici Maria , Rohatiner Ama Z. , Fitzgibbon Jude , Lister T. Andrew , Goff Lindsey K. 
Published: January 2004

SummaryThe prognostic significance of IgH/Bcl2 rearrangement in follicular lymphoma (FL) remains contentious; polymerase chain reaction (PCR) methodology and tissue source variability may account for some inconsistencies. As IgH/Bcl2 major breakpoint region (MBR) sequences may be found in normal blood, an MBR+ result by conventional PCR in blood/bone marrow may not indicate FL. To establish tumour MBR status, 190 lymphoid tissue samples with histologically evident FL (and therefore >1% tumour cells) were examined by real‐time quantifiable PCR; 50% (95/190) had clonal MBR IgH/Bcl2 (MBR was considered clonal when >1%). Overall survival (median = 11·5 years) of MBR+ and MBR− patients was not significantly different.
Monitoring the development of clinical skills during training in a clinical placement
Authors: Pender F. T. , de Looy A. E. 
Published: January 2004

AbstractBackground  The education and training of health care practitioners has undergone recent reform, and indicate that curricula should place emphasis on the development of clinical skills and attitude. The purpose of this study was two‐fold: to define the key skills necessary for a competent dietetic student practitioner and to devise a reliable assessment tool to measure and track performance in these key skill areas throughout the period of clinical placement.Methods  Key clinical skills were identified by a concensus group of experienced dietitians and academic practitioners. An assessment tool was then developed to measure these attributes in 43 students undertaking clinical placement at a number of training centres in Scotland. Development of skills was tracked for the entire duration of placements using the novel assessment tool. The assessment tool used a visual analogue scale (VAS) as the measuring score.Results  A high level of skill attainment was equated with high VAS scores. Performance in three of the four key skills (written skills: r = 0.762, P ≤ 0.001; interviewing skills: r = 0.697, P < 0.001; and dietary assessment technique: r = 0.697, P ≤ 0.001) showed impressive correlation co‐efficients, indicating a striking and significant positive correlation with the length of training. A high skill performance level attainment was achieved by week 16/17 of training.Conclusion  The authors are confident that the assessment tool is valid and reliable and measures skill performance objectively. A high level of skill attainment was observed in most students by about the mid‐point in training: this allows the student to consolidate these skills in the latter stages of training which is in keeping with educational and practice philosophy of placement learning outcomes.
The testing of clinical skills in dietetic students prior to entering clinical placement
Authors: Pender F. T. , de Looy A. E. 
Published: January 2004

AbstractBackground  One of the most important requirements for contemporary education of a health care professional is to develop a framework for theory and practise which results in attainment of professional competencies suitably robust for a lifetime of practise (Howe, 2002). In the context of those educating preregistration dietitians, this offers the challenge of presenting the student with innovative curricula designed to deliver the appropriate level of knowledge and understanding together with emphasis on skill and attitude development. The purpose of this study was to allow preregistration students the opportunity to practise key clinical skills prior to clinical placement and test skills acquisition using the model of an objective structured clinical examination (OSCE).Methods  The learning experience of the student was altered to accommodate a more conceptually‐driven, problem‐centred, case‐based approach. The curriculum was adjusted to incorporate a short clinical skills programme where emphasis was deliberately placed on skill acquisition. At the conclusion of this clinical skills programme, and prior to the students entering clinical placement, skill performance by students was tested using the OSCE. The method of testing was also evaluated by students.Results  The OSCE was delivered to 37 preclinical students. Four of the test candidates (11%) failed in at least one of the skill areas: these students performed similarly during clinical placement. Twenty‐one (57%) students returned the post‐OSCE questionnaire. Twenty (95%) students reported a positive experience; 20 (95%) students reported initial anxiety that diminished as the test progressed.Conclusion  The Project Team was confident with the novel approach taken in re‐designing the curriculum: to include a dedicated clinical skills programme, together with addition of the testing of clinical skills using the OSCE model. These curriculum changes were deemed to be highly appropriate additions to the student experience in determination of skill performance of students prior to clinical placement.
Investigation into the nutritional status, dietary intake and smoking habits of patients with chronic obstructive pulmonary disease
Authors: Cochrane W. J. , Afolabi O. A. 
Published: January 2004

AbstractBackground and aims  Weight loss and reduced fat‐free mass are prevalent amongst patients with chronic obstructive pulmonary disease (COPD). However, the causes of this weight loss are not clear. The aims of this study are to investigate the factors affecting body weight and dietary intake in a group of outpatients with COPD, and to investigate any differences between adequately nourished and malnourished patients.Methods  In 103 stable outpatients, nutritional status was assessed using Body Mass Index (BMI) and upper arm anthropometry. Lung function, smoking status, exercise tolerance, dietary intake, dietary problems and health‐related quality of life were assessed. Patients were classed as either adequately nourished or malnourished.Results  Twenty‐three per cent of subjects were classed as malnourished. The malnourished subjects had lower lung function measurements, suffered more dietary problems and had lower nutritional intake compared with the adequately nourished subjects. They also had poorer fatigue scores. In linear regression analysis, the factors that had the most effect on BMI were a low transfer factor, presence of early satiety, and being a current smoker.Conclusion  Important differences were found between adequately nourished and malnourished subjects. These differences move us closer to understanding how best to screen and treat this group of patients.
The development and evaluation of Student Training, Education and Practice for Dietetics CD‐ROM: a computer‐assisted instruction programme for dietetic students
Authors: Herriot A. M. , Bishop J. A. , Truby H. 
Published: January 2004

AbstractThe Student Training, Education and Practice for Dietetics (STEP‐DIET) CD‐ROM was developed at the University of Surrey to prepare dietetic students for the practical dietetic training component of their Nutrition/Dietetics degree. This study aimed to evaluate student response to the programme and its effectiveness as a teaching tool, based on the evaluation framework of D.L. Kirkpatrick (Evaluating a Course, 2nd edn. London, Kogan Page). Quantitative and qualitative methodologies were employed, with 41 dietetic students, separated by year group, completing questionnaires and taking part in six focus groups, at the University of Surrey. Student attitudes towards the instruction method and the STEP‐DIET programme itself were investigated, in conjunction with their perceived learning achievements.Students rated the programme highly in terms of design and content, however, there was a reluctance to accept computer‐assisted instruction (CAI) as a sole teaching method. A number of learning achievements relevant to dietetic practice were reported including a perceived increase in ability to conduct a dietetic interview and an increased understanding of the management of Type 2 diabetes. In general students reacted positively to the STEP‐DIET programme and it was perceived by students to be effective in preparing them for the practical component of their dietetic training.
A survey to assess physical activity promotion by Registered Dietitians
Authors: McKenna J. , Henderson L. , Baic S. 
Published: January 2004

AbstractBackground  Convincing evidence has emerged in recent years for the role of physical activity (PA) in the prevention and treatment of many chronic diseases. These include both physical and mental health problems, which are likely to be encountered by practicing dietitians. This study aimed to identify whether NHS based Registered Dietitians (RDs) currently promote PA to their patients and if so, how they do it and with which patients.Method  An anonymous questionnaire sent to 516 RDs in NHS teaching hospitals achieved a 77% (n = 397) return rate.Results  Ninety‐three per cent of respondents reported regularly promoting PA particularly with new patients. Among active PA promoters, 87% reported encouraged daily accumulation of PA, 50% focused on sport and exercise and 52% referred patients to GPs or Physiotherapists for advice.Distinctive levels and styles of PA promotion were found to be related to levels of recent training in the field although fewer than one in four had actually received any formal training.Conclusions  A high interest in further PA‐specific training (95% of all respondents), together with high variability in the type and quality of advice suggests the need to develop further in‐service training specifically for RDs.
Impact of tea drinking on iron status in the UK: a review
Authors: Nelson M. , Poulter J. 
Published: January 2004

AbstractBackground The aims of this review are (1) to evaluate the literature on the likely impact of tea drinking on the iron status of different groups within the UK population and (2) to formulate targeted and evidence based advice on tea drinking in the context of iron nutrition in different groups of people.Method A literature search identified 35 references specific to the effects of black tea on iron absorption and iron nutrition plus one recent review article. Each study was assessed in terms of methodogical quality and relevance to the tea drinking patterns of the UK population.Results There is clear evidence to show that tea drinking limits the absorption of nonhaem iron. However, there are few studies which have assessed the influence of tea drinking on indicators of iron status. There are no intervention studies and the conclusions reported in this review are based on 12 observational studies mostly from other countries. These studies have reported either significant negative correlations between tea drinking and blood indicators of iron status or more cases of anemia in tea drinkers compared with nontea drinkers. Many of the studies reviewed report additional relationships between iron status indices and other factors (both dietary and nondietary), highlighting the complexity of influences on iron absorption and iron status.Conclusion From the available evidence there is no need to advise any restriction on tea drinking in healthy people with no risk of iron deficiency. In groups at risk of iron deficiency the advice should be to drink tea between meals and to wait at least 1 h after eating before drinking tea.
The opinion of Dutch dietitians about functional foods
Authors: De Jong N. , Hoendervangers C. T. , Bleeker J. K. , Ocké M. C. 
Published: January 2004

AbstractObjective  To obtain information about Dutch dietitian's attitudes, perceived knowledge, training preferences, counselling procedures, opinions about post‐launch monitoring, and personal consumption of functional foods.Design  A self‐administered, 62‐item, postal survey in 2002.Subjects  Five hundred randomly selected registered dietitians. The response rate was 49% (n = 238).Results  The responders (mean age ± SD: 40 ± 9 years) had regular contact with clients (90%), and many (71% of 90%) advised about functional food use. Sixty‐nine per cent hardly consumed any functional food themselves. Eighty‐seven per cent of the responders would greatly appreciate courses given by scientists. Confusion existed about usage practices, target groups, safety, efficacy, and claims: between 42 and 89% agreed with the statements about uncertainties. Nonetheless, 69% felt that functional foods could theoretically contribute to good bodily functioning. Ninety per cent thought post‐launch monitoring (PLM) important, but ideas about a common dietetic contribution to PLM did not emerge.Conclusions  Although functional foods potentially contribute to a healthful diet, there is still confusion among dietitians about claims, safety, efficacy and product‐handling aspects. It is time to meet dietitians’ repeated requests to provide education by noncommercial experts. In the meantime, dietitians themselves should have more say in the PLM debate because they should and could play an important role.
Test strip detection of Wuchereria bancrofti amplified DNA in wild‐caught Culex pipiens and estimation of infection rate by a PoolScreen algorithm
Authors: Helmy Hanan , Fischer Peter , Farid Hoda A. , Bradley Mark H. , Ramzy Reda M. R. 
Published: January 2004

SummaryBancroftian filariasis is targeted for elimination in the Nile Delta of Egypt. Improved simple methods are needed for monitoring Wuchereria bancrofti infection in the mosquito vector and thereby the success of elimination programmes. We evaluated the performance of the SspI‐PCR assay combined with a DNA Detection Test StripTM method and used the PoolScreen algorithm method for estimating mosquito infection rates. A total of 769 indoor‐resting Culex pipiens were captured in 79 randomly selected houses from a filaria‐endemic village in the Nile Delta of Egypt (24.4% antigenaemia and 8.6% microfilaraemia). Collected mosquitoes were pooled by house, and assayed by the SspI‐PCR. Amplified parasite DNA was detected by both electrophoresis of agarose gel stained with ethidium bromide (EtBr) and by test strips. PCR based on EtBr and test strip methods identified 43 (54.4%) and 45 (56.9%) houses, respectively, as being filaria positive. The minimum mosquito infection rate, assuming one infected female/pool was 6.85% by the PCR test strips. Mosquito infection rate calculated by the PoolScreen2 algorithm software amounted to 8.1% [95% confidence interval 5.85, 10.47]. Because it is faster and safer, the PCR test strip is a practical tool, especially when combined with the PoolScreen algorithm method, for xenomonitoring the success of elimination programmes.
Pregnancy interval and delivery outcome among HIV‐seropositive and HIV‐seronegative women in Kisumu, Kenya
Authors: van Eijk Anna M. , De Cock Kevin M. , Ayisi John G. , Rosen Daniel H. , Otieno Juliana A. , Nahlen Bernard L. , Steketee Richard W. 
Published: January 2004

SummaryObjective  A short pregnancy interval (PI) has been associated with increased child mortality, but mechanisms are unclear. We studied factors associated with PI and the effect of PI on birthweight and haemoglobin.Methods  Information was analysed from 2218 multigravidae who were recruited at the prenatal clinic (1758) or in the labour ward (460) of the Provincial Hospital in Kisumu between June 1996 and July 2000 for a study to assess the interaction between placental malaria and vertical HIV transmission.Results  The HIV prevalence was 28.9%. HIV seropositivity, older age, being unmarried, and <8 years of education were associated with a prolonged PI; among all women, a stillbirth, abortion, or death of a liveborn child as outcome of the previous pregnancy, and death of a child other than the last born among HIV‐seronegative women, were associated with a shortened PI. No significant effect of short PI (an interval <24 months) on low birth weight (LBW), prematurity, small‐for‐gestational‐age infants or maternal anaemia was evident. An abortion, stillbirth, or death of a liveborn child as outcome of the previous pregnancy was associated at the present delivery with LBW among HIV‐seronegative women [adjusted odds ratio (AOR) 3.33, 95% confidence interval (CI) 1.63–6.81], and a low haemoglobin (<11 g/dl) among HIV‐seropositive women (AOR 2.01, 95% CI 1.05–4.03 in the third trimester).Conclusion  Public health efforts to ensure ‘adequate’ birth spacing may run contrary to family planning decisions to replace a deceased child and may be spent on prenatal issues like prevention of anaemia, and vertical HIV transmission.