bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epstein‐Barr virus‐associated familial Hodgkin lymphoma: paediatric onset in three of five siblings
Authors: Kamper Peter M. , Kjeldsen Eigil , Clausen Niels , Bendix Knud , Hamilton‐Dutoit Stephen , D'Amore Francesco 
Published: July 2005

SummaryWe report familial Hodgkin lymphoma (FHL) in a family with five children, of which three were human leucocyte antigen (HLA) class I identical. These three siblings were diagnosed with Epstein‐Barr virus (EBV)‐positive Hodgkin lymphoma within a 6‐year period. All three were treated with chemo‐ and/or radiotherapy and are presently in complete remission. None of the children had evidence of overt immunodeficiency or autoimmune disease. This case contributes to the existing material on FHL and implies a role for both HLA class I antigens and EBV infection of the tumour cell population in the pathogenesis of some cases of FHL.
Subtyping of natural killer cell cytotoxicity deficiencies in haemophagocytic lymphohistocytosis provides therapeutic guidance
Authors: Horne AnnaCarin , Zheng Chengyun , Lorenz Ingrid , Löfstedt Martina , Montgomery Scott M. , Janka Gritta , Henter Jan‐Inge , Marion Schneider E. 
Published: July 2005

SummaryThe familial form of haemophagocytic lymphohistiocytosis (HLH) is a fatal disease, with allogeneic stem cell transplantation (SCT) being the only curative treatment. In contrast, patients with secondary (infection‐associated) HLH usually do not require SCT. Since it often is difficult to distinguish primary and secondary HLH, we wanted to identify a tool that provides guidance on whether SCT is required. The clinical outcome of 65 HLH patients was analysed in relation to the recently reported four types of defects in natural killer (NK)‐cell cytotoxicity in HLH. None (0%) of the 36 patients with NK‐cell deficiency type 3 attained a sustained (1‐year) remission after stopping therapy without receiving SCT, in contrast to 45% (13/29) non‐type 3 patients (P < 0·001). Most type 3 patients (22/36) underwent SCT (14/22, 64% are alive), whereas 11 of 14 that did not receive SCT died, and the three others had received HLH‐therapy during the last year of follow‐up. Of 54 patients analysed for perforin expression and/or mutation, the five with perforin deficiency were all type 3 patients. The data suggests that HLH patients with NK‐cell deficiency type 3 will probably require SCT to survive. Thus, NK‐cell deficiency classification may provide valuable guidance in judging whether an HLH‐patient needs SCT.
Evidence for a link between sphingolipid metabolism and expression of CD1d and MHC‐class II: monocytes from Gaucher disease patients as a model
Authors: Balreira Andrea , Lacerda Lúcia , Miranda Clara Sá , Arosa Fernando A. 
Published: July 2005

SummaryGaucher disease (GD) is an autosomal recessive inherited defect of the lysosomal enzyme glucocerebrosidase (GluCerase) that leads to glucosylceramide (GluCer) accumulation. We previously demonstrated the existence of imbalances in certain lymphocyte populations in GD patients. We now show that GluCerase‐deficient monocytes from GD patients or monocytes from healthy subjects treated with conduritol‐B‐epoxide (CBE), an irreversible inhibitor of GluCerase activity, display high levels of surface expression of the lipid‐binding molecule CD1d. GluCerase‐deficient monocytes from GD patients also showed increased surface expression of major histocompatibility complex (MHC)‐class II, but not of other lysosomal trafficking molecules, such as CD63 and MHC‐class I. However, CD1d and MHC‐class II mRNA levels were not increased. GluCerase‐deficient monocytes from GD patients undergoing enzyme replacement therapy also exhibited increased levels of CD1d and MHC‐class II and imbalances in the percentage of CD4+, CD8+, and Vα24+T cells. Interestingly, follow‐up studies revealed that enzyme replacement therapy induced a decrease in MHC‐class II expression and partial correction of the CD4+T cell imbalances. These results reveal a new link between sphingolipid accumulation in monocytes and the expression of certain MHC molecules that may result in imbalances of regulatory T cell subsets. These immunological anomalies may contribute to the clinical heterogeneity in GD patients.
Polymorphisms in cytochrome P450 17A1 and risk of non‐Hodgkin lymphoma
Authors: Skibola Christine F. , Lightfoot Tracy , Agana Luz , Smith Alex , Rollinson Sara , Kao Andrew , Adamson Peter , Morgan Gareth J. , Smith Martyn T. , Roman Eve 
Published: July 2005

SummaryBroad cross‐talk exists between the endocrine and immune systems. Estrogen receptor expression in lymphocytes suggests that hormonal modulation may influence lymphoma risk. Analysis of genetic polymorphisms that affect oestrogen production, such as cytochrome P450 17A1 (CYP17A1) −34T>C, may provide insight into oestrogen's role in lymphomagenesis. CYP17A1−34T>C and CYP17A1 IVS2 105A>C polymorphisms were analyzed in a non‐Hodgkin lymphoma (NHL) population‐based case–control study. The CYP17A1−34CC genotype was positively associated with NHL [odds ratio (OR) = 1·44, 95% confidence interval (CI) 1·02–2·03], particularly diffuse large B‐cell lymphoma (OR = 1·76, CI 1·14–2·71). Associations of CYP17A1 polymorphisms with increased risk of NHL suggest a role for oestrogen in lymphomagenesis.
Fusion of dendritic cells with multiple myeloma cells results in maturation and enhanced antigen presentation
Authors: Vasir Baldev , Borges Virginia , Wu Zekui , Grosman Daren , Rosenblatt Jacalyn , Irie Masaki , Anderson Kenneth , Kufe Donald , Avigan David 
Published: July 2005

SummaryDendritic cells (DCs) are potent antigen‐presenting cells that are uniquely capable of inducing primary immune responses. Although tumour cells may directly inhibit DC maturation, exposure to tumour products may also result in their activation. Fusions of cancer cells and DCs are being explored as cancer vaccines. The effect of tumour cell fusion on DC maturation and their functional characteristics has not been defined. In the present study, immature and mature DC generated from human CD34+ and peripheral blood precursors were fused to multiple myeloma cells in the presence of polyethylene glycol. Fusion of both immature and mature DCs with tumour cells resulted in an activated phenotype. In this regard, fusion cells expressed interleukin‐12, a cytokine essential for the induction of T‐helper cell type 1 immunity. In contrast to immature DCs, fusion cells also strongly expressed CC‐chemokine receptor R7, which is responsible for DC migration to draining lymph nodes. Fusions generated with both immature and mature DCs also potently stimulated T‐cell expression of γ‐interferon and cytotoxic T lymphocyte killing of tumour targets. These findings demonstrate that tumour cell fusion induces DC maturation and the development of an activated phenotype necessary for their effectiveness as cancer vaccines.
The course of ADAMTS‐13 activity and inhibitor titre in the treatment of thrombotic thrombocytopenic purpura with plasma exchange and vincristine
Authors: Böhm Martina , Betz Christoph , Miesbach Wolfgang , Krause Manuela , von Auer Charis , Geiger Helmut , Scharrer Inge 
Published: July 2005

SummaryThe therapeutic efficacy of plasma exchange (PE) in thrombotic thrombocytopenic purpura (TTP) is attributed to the restoration in ADAMTS‐13 (a disintegrin and metalloproteinase with thrombospondin motif‐13) activity by substitution of the enzyme and removal of ADAMTS‐13‐neutralizing autoantibodies. We explored this rationale by analysing ADAMTS‐13 activity and corresponding inhibitor levels during PE‐treatment in 27 episodes from 23 adults with TTP. All patients with an initial episode of TTP (n = 14) and nine of 11 patients with a relapse showed severe ADAMTS‐13 deficiency. ADAMTS‐13 inhibitors were detected in 81% of these patients. Twenty‐one patients responded to PE‐therapy and two patients died. For patients with severe ADAMTS‐13 deficiency, 15 patients (71%) showed a PE‐induced recovery in ADAMTS‐13 activity and six patients (29%) had persistent severe ADAMTS‐13 deficiency despite clinical response. Three patients with recurrent TTP demonstrated a permanent increase in inhibitor titre during therapy. Six patients (43%) with an initial episode of TTP displayed a transient increase in inhibitor titre during PE‐therapy, which was associated with deterioration in clinical and haematological symptoms of TTP. Treatment with vincristine induced an immediate increase in platelet count and ADAMTS‐13 activity in seven of eight patients. We conclude that ADAMTS‐13 activity and inhibitor levels, as measured using current methodology, do not solely determine the clinical course of TTP.
Long‐term outcomes of previously untreated myeloma patients: responses to induction chemotherapy and high‐dose melphalan incorporated within a risk stratification model can help to direct the use of novel treatments
Authors: Alvares Caroline L. , Davies Faith E. , Horton Clive , Patel Gita , Powles Ray , Sirohi Bhawna , Zuha Roslin , Gatt Alex , Saso Radovan , Treleaven Jennifer G. , Dearden Claire E. , Potter Michael N. , Ethell Mark E. , Morgan Gareth J. 
Published: July 2005

SummaryInduction chemotherapy followed by high‐dose melphalan (HDM) is the standard treatment for fitter patients with myeloma. The place of bortezomib and the thalidomide analogues within this treatment paradigm is yet to be established. We sought to identify patients who may benefit from the introduction of novel agents during their initial management. An intention‐to‐treat analysis was performed on 383 patients with newly diagnosed myeloma eligible for HDM to determine whether the extent of response to induction therapy and HDM correlated with long‐term survival. Early response [complete response (CR) and partial response (PR)] to induction therapy was predictive of overall survival (OS) [median OS, 7·47 years for responders (CR and PR) versus 4·89 years for non‐responders; P = 0·035]. The attainment of CR at 3 months post‐HDM correlated with a prolonged progression‐free survival (PFS) (median PFS, 7·4 years in CR group versus 5·3 years in non‐CR group; P = 0·023). This data suggests that, at every stage of treatment, the aim should be to achieve CR. Patients with suboptimal responses could be offered alternative therapy. We propose a multiparametric risk‐adapted model that includes response to induction chemotherapy and HDM, for identifying patients who may benefit from novel approaches to treatment.
Aiming towards effective preventive medicine against Japanese cedar pollinosis: epidemiology, patient investigation and integrated research including genotype analyses
Authors: Terada N. , Kobayashi T. , Suzuki T. , Yamazaki K. , Izuhara K. , Konno A. 
Published: July 2005

SummaryEnvironmental rather than genetic factors appear to play the major role in the recent increased prevalence of Japanese cedar pollinosis in Japan. However, investigating the genes that determine IgE levels and analysing gene polymorphisms may assist in finding new methods of treatment and establishing preventive medicine against this disease. Among a total of 219 asymptomatic individuals who were anti‐Japanese cedar pollen IgE antibody positive as determined by radioallergosorbent test (RAST), only a handful subsequently developed symptoms of Japanese cedar pollinosis or secondary onset of Japanese cedar pollinosis over 5–14 years of follow‐up. Among those who subsequently developed secondary onset of disease, >50% were found to have high initial RAST scores, suggesting that the incidence of Japanese cedar pollinosis is correlated with RAST score. Hence, it may be prudent to advise asymptomatic individuals with high RAST scores to avoid exposure to Japanese cedar pollen so as to delay onset of the disease. Analysis of sequence variants of the FcɛRIβ gene revealed that patients with nasal allergy exhibit a single‐nucleotide polymorphism in which the amino acid at 237 of the intracellular domain changes from glutamine to glycine more frequently than individuals without nasal allergy. Furthermore, Il homo polymorphism of the IL‐4Rα gene is associated with higher serum nonspecific IgE and Japanese cedar pollen‐specific IgE levels than are seen in individuals showing Il,Val hetero and Val homo expression types. When the age of pollinosis onset was compared among these three genotypes, it was found to be significantly lower among Il homo type than the other two expression types, suggesting that Il homo type individuals seem characteristically pre‐disposed to early onset of pollinosis. Studies comparing eosinophil‐associated gene polymorphism in healthy and pollinosis phenotypes have revealed several relationships among the various genotypes and specific disease parameters and suggest that Eotaxin G (123G/A) and IL5 (–703C/T) genotypes can affect the timing of symptom onset after sensitization as well as nasal mucosal hyper‐responsiveness.
Role of T cells in allergic rhinitis
Authors: Horiguchi S. , Okamoto Y. 
Published: July 2005

SummaryA characteristic feature of allergic rhinitis (AR) is the production of allergen‐specific IgE antibodies. It is widely accepted that the induction of antigen‐specific type 2 CD4+ helper cells (Th2) is a key event in this disease. Allergen‐specific T cell–B cell interaction is indispensable for the induction of human IgE synthesis. Th2 cells also cause influx and activation of eosinophils, mast cells and basophils. Th2 cytokine‐inducing cells play a major role in AR; this is known as the ‘Th2 paradigm’. In this review, we examine the Th1/Th2 cell dysregulation of AR and discuss new treatment approaches to improve this dysregulation.
Roles of protein tyrosine kinase Syk in nasal polyps
Authors: Yamada T. , Takahashi N. , Sunaga H. , Narita N. , Yamamoto H. , Fujieda S. 
Published: July 2005

SummaryThe non‐receptor protein tyrosine kinase Syk is widely expressed and plays an important role in intracellular signal transduction in haematopoietic cells including B cells, mast cells, eosinophils, platelets, macrophages, neutrophils and T cells. We found that Syk is expressed in human nasal polyp tissue‐derived fibroblasts and plays a critical role in chemokine production and activation of c‐Jun N‐terminal kinase 1 stimulated with lipopolysaccharide or IL‐1. In mast cells, cross‐linking FcɛRI via IgE bound to multivalent antigen induces tyrosine phosphorylation of immunoreceptor tyrosine‐based activation motifs, and binds and modifies the activity of Syk, thereby initiating downstream signalling. In eosinophils, Syk is essential for activating the antiapoptotic pathway and generating reactive oxygen intermediates in response to Fcγ receptor engagement. In nasal polyps, Syk inhibition might influence the levels and function of specific IgE to Staphylococcus aureus enterotoxins that are thought to drive local eosinophilic inflammation therein. The regulation of Syk expression may prove to be a useful strategy in the treatment of airway diseases.
Distinct role for nasal fibroblasts in initiation of the eosinophilic inflammatory response
Authors: Nonaka M. , Pawankar R. , Fukumoto A. , Ogihara N. , Sakanushi A. , Yagi T. 
Published: July 2005

SummaryBackground
It is now generally accepted that type 2 T helper (Th2) cytokines and some chemoattractants play essential roles in the pathogenesis of nasal polyposis, a disorder characterized by chronic eosinophilic inflammation and varying degrees of structural abnormalities. The mechanisms that cause the predominance of eosinophil infiltration in nasal polyposis have yet to be clarified; however, there is growing evidence that fibroblasts could be major sources of chemotactic factors for eosinophils. As the first point of contact for incoming potentially injurious agents such as microorganisms and their breakdown products including lipopolysaccharide (LPS), the nasal mucosa is exposed to many environmental pathogens.Objective
We investigated whether airway fibroblasts produce the CC chemokines regulated upon activation, normal T cell expressed and secreted (RANTES) and eotaxin when stimulated with LPS and/or Th2 cytokines such as IL‐4 and examined whether there is any heterogeneity among fibroblasts from different airway tissue sites with regard to CC chemokine expressions.Methods
Fibroblast cell lines were established from human airway biopsy tissues. The expression of chemokine mRNA and amount of chemokines in supernatants were measured.Results
LPS stimulated the synthesis of RANTES in nasal fibroblasts but not in pharyngeal, tracheal, bronchial and lung fibroblasts. Combined stimulation with LPS and IL‐4 synergistically induced the production of eotaxin in nasal fibroblasts but not in lung fibroblasts.Conclusions
These results indicate distinct contributions of nasal fibroblasts to eosinophilic inflammation in the airway.
Using smart card technology to monitor the eating habits of children in a school cafeteria: 1. Developing and validating the methodology
Authors: Lambert N. , Plumb J. , Looise B. , Johnson I. T. , Harvey I. , Wheeler C. , Robinson M. , Rolfe P. 
Published: July 2005

AbstractObjective  The aim of the study was to test the feasibility of using smart card technology to track the eating behaviours of nearly a thousand children in a school cafeteria.Methods  Within a large boys’ school a smart card based system was developed that was capable of providing a full electronic audit of all the individual transactions that occurred within the cafeteria. This dataset was interfaced to an electronic version of the McCance and Widdowson composition of foods dataset. The accuracy of the smart card generated data and the influence of portion size and wastage were determined empirically during two 5‐day trials.Results  The smart card system created succeeded in generating precise data on the food choices made by hundreds of children over an indefinite time period. The data was expanded to include a full nutrient analysis of all the foods chosen. The accuracy of this information was only constrained by the limitations facing all food composition research, e.g. variations in recipes, portion sizes, cooking practices, etc. Although technically possible to introduce wastage correction factors into the software, thereby providing information upon foods consumed, this was not seen as universally practical.Conclusion  The study demonstrated the power of smart card technology for monitoring food/nutrient choice over limitless time in environments such as school cafeterias. The strengths, limitations and applications of such technology are discussed.
Can we use mid upper arm anthropometry to detect malnutrition in medical inpatients? A validation study
Authors: Burden S. T. , Stoppard E. , Shaffer J. , Makin A. , Todd C. 
Published: July 2005

AbstractBackground and aims  Mid upper arm anthropometry (MUAA) is often used as a measure of nutritional status to detect changes in body composition. The aim of this study was to investigate the reliability and validity of MUAA including mid arm circumference (MAC) and triceps skin fold thickness (TSFT) to determine the usefulness in clinical practice.Method  We measured MUAA in 158 consecutive admissions along with subjective global assessment (SGA) and body mass index (BMI). Inter‐ and intra‐rater reliability was evaluated in an additional 50 patients.Results  The sensitivity and specificity of MUAA <5th percentile was compared with SGA and BMI. MAC and TSFT had a low sensitivity and a high specificity with low positive predictive values when compared with criterion values which were BMI ≤18 and SGA‐C. The intra‐class correlation coefficient for inter‐ and intra‐rater reliability for MAC were 0.98 (95% CI 0.96–0.98) and 0.99 (95% CI 0.98–0.99) respectively and for TSFT were 0.97 (95% CI 0.91–0.97) and 0.98 (95% CI 0.95–0.98) respectively.Conclusion  MUAA <5th percentile had a high specificity but low sensitivity when compared with indicators of malnutrition. Although MUAA could be reliably measured, it has poor validity and is thus unlikely to be a good predictor of clinical outcome. Percentiles based on healthy populations do not generalize well to the individuals seen in clinical practice.
Does the provision of cooled filtered water in secondary school cafeterias increase water drinking and decrease the purchase of soft drinks?
Authors: Loughridge J. L. , Barratt J. 
Published: July 2005

AbstractBackground  Secondary school students often do not drink sufficient quantities of water during the school day to prevent dehydration, promote learning and good health. The study aimed to measure the effect of health promotion and the free provision of cooled filtered water on the consumption of water and soft drinks. It also aimed to explore students’ views of drinking water provision.Methods  A study was conducted with three secondary schools in North Tyneside. Over a 3 month period one school was given cooled filtered water and active promotion (W + P), another had water only (W). The control school (C) took part in post‐intervention focus group work.Results  The average volume of water drunk by students, in school ‘W + P’ was greater (P = 0.05) than that drunk in school ‘W’ and control school ‘C’. The volume of soft drinks purchased by students in all three schools before and during the intervention remained static. Focus group data revealed that students viewed their existing water provision as poor and wanted sufficient supplies of cooled filtered water in school.Conclusions  This pilot study indicates that active promotion of water drinking increased consumption of water by secondary school students. Further developments of the project are suggested.
A new stereological principle for test lines in three‐dimensional space
Authors: CRUZ‐ORIVE L. M. 
Published: July 2005

SummaryA new principle is presented to generate isotropic uniform random (IUR) test lines hitting a geometric structure in three‐dimensional space (3D). The principle therefore concerns the estimation of surface area, volume, membrane thickness, etc., of arbitrary structures with piecewise smooth boundary. The principle states that a point‐sampled test line on an isotropic plane through a fixed point in 3D is effectively an invariant test line in 3D. Particular attention is devoted to the stereology of particles, where an alternative to the surfactor method is obtained to estimate surface area. An interesting case arises when the particle is convex. The methods are illustrated with synthetic examples.
Electron and ion imaging of gland cells using the FIB/SEM system
Authors: DROBNE D. , MILANI M. , ZRIMEC A. , LEŠER V. , BERDEN ZRIMEC M. 
Published: July 2005

SummaryThe FIB/SEM system was satisfactorily used for scanning ion (SIM) and scanning electron microscopy (SEM) of gland epithelial cells of a terrestrial isopod Porcellio scaber (Isopoda, Crustacea). The interior of cells was exposed by site‐specific in situ focused ion beam (FIB) milling. Scanning ion (SI) imaging was an adequate substitution for scanning electron (SE) imaging when charging rendered SE imaging impossible. No significant differences in resolution between the SI and SE images were observed. The contrast on both the SI and SE images is a topographic. The consequences of SI imaging are, among others, introduction of Ga+ ions on/into the samples and destruction of the imaged surface. These two characteristics of SI imaging can be used advantageously. Introduction of Ga+ ions onto the specimen neutralizes the charge effect in the subsequent SE imaging. In addition, the destructive nature of SI imaging can be used as a tool for the gradual removal of the exposed layer of the imaged surface, uncovering the structures lying beneath. Alternative SEM and SIM in combination with site‐specific in situ FIB sample sectioning made it possible to image the submicrometre structures of gland epithelium cells with reproducibility, repeatability and in the same range of magnifications as in transmission electron microscopy (TEM). At the present state of technology, ultrastructural elements imaged by the FIB/SEM system cannot be directly identified by comparison with TEM images.