bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impaired interaction of α‐haemoglobin‐stabilising protein with α‐globin termination mutant in a yeast two‐hybrid system
Authors: Turbpaiboon Chairat , Limjindaporn Thawornchai , Wongwiwat Wiyada , U‐Pratya Yaowalak , Siritanaratkul Noppadol , Yenchitsomanus Pa‐thai , Jitrapakdee Sarawut , Wilairat Prapon 
Published: November 2005

Summary α‐Thalassaemia caused by α‐globin gene termination codon mutations (αT‐globin) has been explained by their inherent mRNA instability and by oxidative damage arising from the presence of membrane‐bound αT‐globin chains. To better understand the latter phenomenon, a yeast two‐hybrid system was used to assay the interaction between αT‐globin and its molecular chaperone, α‐haemoglobin‐stabilising protein (AHSP) and impaired binding of αT‐globin with AHSP compared with αwild‐type‐globin was observed.
Herpes simplex virus 1 infection induces the expression of proinflammatory cytokines, interferons and TLR7 in human corneal epithelial cells
Authors: Li Hui , Zhang Jing , Kumar Ashok , Zheng Mei , Atherton Sally S. , Yu Fu‐Shin X. 
Published: November 2005

SummaryHerpetic epithelial and stromal keratitis is a sight‐threatening ocular infection. To study the role of the epithelium in the innate response to herpes simplex virus 1 (HSV‐1) infection of the cornea, we used a telomerase‐immortalized human corneal epithelial cell (HCEC) line, HUCL, and primary HCECs as a model and infected the cells with HSV‐1 (KOS strain). HSV‐1 infection of HCECs resulted in a two‐phase activation of nuclear factor‐kappaB (NF‐κB), JNK and p38, with the first peak at 1–4 hr and a second peak at 8 hr. Concomitant with the first peak of activation, transcriptional expression of interleukin (IL)‐6, IL‐8, tumour necrosis factor (TNF)‐α and interferon (IFN)‐β was rapidly induced in HSV‐1‐infected cells. HSV‐1 infection also induced the production of IL‐6, IL‐8, and TNF‐α in both HUCL cells and primary HCECs. Coincident with the second phase of NF‐κB activation in HSV‐1‐infected HCECs, the expression of Toll‐like receptor 7 (TLR7) was induced, whereas the level of TLR3 was greatly down‐regulated. Thus, in response to HSV‐1 infection, HCECs produce proinflammatory cytokines, leading to infiltration, and IFNs to enhance the antiviral activity in the cornea, probably through sequential activation of TLRs.
A canine model of cutaneous late‐phase reactions: prednisolone inhibition of cellular and cytokine responses
Authors: Pucheu‐Haston Cherie M. , Shuster Dale , Olivry Thierry , Brianceau Philippe , Lockwood Patrick , McClanahan Terrill , de Waal Malefyt Rene , Mattson Jeanine D. , Hammerberg Bruce 
Published: November 2005

SummaryImmunoglobulin E (IgE)‐mediated late‐phase reactions can be induced in atopic humans by intradermal injection of relevant allergens or anti‐IgE antibodies. The histology of these reactions resembles that of naturally occurring atopic dermatitis. Strikingly similar responses can be induced in dogs, suggesting that a canine model could prove valuable for preclinical investigation of drugs targeting late‐phase reactions. This study was designed to characterize the cellular, cytokine and chemokine responses after intradermal anti‐IgE injection in untreated and prednisolone‐treated dogs. Normal beagles were untreated or treated with prednisolone before intradermal injection of polyclonal rabbit anti‐canine IgE or normal rabbit IgG. Biopsies were taken before injection and 6, 24 and 48 hr after injection. Samples were evaluated by histological and immunohistochemical staining, as well as by real‐time quantitative polymerase chain reaction analysis. Dermal eosinophil and neutrophil numbers increased dramatically within 6 hr after injection of rabbit anti‐canine IgE, and remained moderately elevated at 48 hr. The numbers of CD1c+ and CD3+ mononuclear cells were also increased at 6 hr. The real‐time quantitative polymerase chain reaction demonstrated marked increases in mRNA expression for interleukin‐13 (IL‐13), CCL2, CCL5 and CCL17. Levels of mRNA for IL‐2, IL‐4, IL‐6 and IFN‐γ did not change within the limits of detection. Prednisolone administration suppressed the influx of neutrophils, eosinophils, CD1c+ and CD3+ cells, as well as expression of IL‐13, CCL2, CCL5 and CCL17. These data document the cytokine and chemokine responses to anti‐IgE injection in canine skin, and they demonstrate the ability of the model to characterize the anti‐inflammatory effects of a known therapeutic agent.
A novel mechanism of nuclear factor‐κB regulation by adenoviral protein 14·7K
Authors: Carmody Ruaidhrí J. , Maguschak Kimberly , Chen Youhai H. 
Published: November 2005

SummaryViruses have evolved many different ways to evade immune attacks. The adenoviral E3 protein 14·7K effectively inhibits antiviral immunity and inflammation. However, the underlying mechanism for this effect is unclear. Here we show that 14·7K is a potent inhibitor of nuclear factor (NF)‐κB transcriptional activity following Toll‐like receptor (TLR) or tumour necrosis factor (TNF) receptor signalling. The inhibition of the NF‐κB activity occurs downstream of IκBα degradation and NF‐κB translocation into the nucleus. Analysis of NF‐κB DNA binding reveals that 14·7K specifically inhibits p50 homodimer DNA binding and that this inhibition is mediated through the interaction of 14·7K with p50. We propose that 14·7K inhibits NF‐κB activity through directly blocking p50 binding to DNA and that this is the basis for its anti‐inflammatory properties. Our data also indicate a role for p50 homodimer‐dependent transcription in inflammation.
Molecular characterization of an arthritogenic collagen peptide interacting with I‐Ar
Authors: Sakurai Yoshihiko , Tang Bo , Rosloniec Edward F. , Stuart John M. , Kang Andrew H. , Myers Linda K. 
Published: November 2005

SummaryCollagen‐induced arthritis (CIA) is an autoimmune arthritis that can be elicited by the immunization of genetically susceptible strains of mice with type II collagen (CII). We have analysed the molecular interactions that occur between an arthritogenic T‐cell determinant CII (442–457) and the murine class II susceptibility allele I‐Ar. To determine which amino acid residues within the CII (442–457) sequence are responsible for binding to I‐Ar, a soluble I‐Ar : IgG2aFc fusion protein–peptide binding assay was developed. Various concentrations of analogue peptides were tested for their ability to compete with biotinylated CII (607–622) for binding to I‐Ar, thereby establishing a relative comparison of the binding affinities among these analogues. Analogue peptides with substitutions at positions 447 (Ala → Val), 448 (Gly → Ala) and 451 (Gly → Ala) bound poorly to the I‐Ar molecule. These data suggest that positions 447, 448 and 451 on CII are the major anchor points to I‐Ar molecules. In cytokine assays, only substitutions within positions 445–454 decreased the interferon‐γ production by T cells. These data narrow the core of the arthritogenic T‐cell determinant to CII (445–454). Identification of the molecular interactions involved in T‐cell recognition of CII should lead to antigen‐specific means of inhibiting autoimmune arthritis.
Activated T cells express the OX40 ligand: requirements for induction and costimulatory function
Authors: Mendel Itzhak , Shevach Ethan M. 
Published: November 2005

SummaryOX40/OX40 ligand (OX40L) interactions have been shown to exert potent costimulatory effects on T‐cell activation. OX40 expression is transiently up‐regulated on T cells following T‐cell receptor engagement, while OX40L is expressed on antigen‐presenting cells following activation. Although expression of the OX40L by T cells has been reported, the requirements for induction of OX40L on T cells have not been studied in detail. Here, we demonstrate that the OX40L can be induced on murine CD4+ and CD8+ T cells after 6 days of culture under T helper type 1 (Th1) conditions, but not under Th2 conditions. Induction of OX40L expression required a high concentration of interleukin‐12 (IL‐12), was not seen in the presence of interferon‐γ, and was dependent on signal transducer and activator of transcription type 4 (STAT4). Notably, induction of OX40L on T cells was only seen at very low concentrations of antigen or anti‐CD3. T‐cell‐expressed OX40L was fully capable of delivering a potent costimulatory signal that enhanced the proliferation of CD4+ T cells as well as promoted their differentiation to Th2 cells. OX40L expression could also be induced on CD4+ T cells in vivo following immunization with low‐dose antigen and an IL‐12 inducer. OX40/OX40L interactions between antigen‐specific T cells may occur in T‐cell zones in lymph node and spleen when OX40L expression has diminished on APC. Costimulation by T‐cell‐expressed OX40L may result in deviation of a Th1 response to a Th2 response under conditions where T cells are exposed to low concentrations of foreign or autoantigens in the presence of high concentrations of IL‐12.
Role of matrix metalloproteinase‐7 in the modulation of a Chlamydia trachomatis infection
Authors: Pal Sukumar , Schmidt Amy P. , Peterson Ellena M. , Wilson Carole L. , de La Maza Luis M. 
Published: November 2005

SummaryTo determine the role of matrix metalloproteinase‐7 (MMP‐7) in the pathogenesis of chlamydial infection, C57BL/6 wild‐type (WT) and MMP‐7 knockout (KO) mice were infected intravaginally with Chlamydia trachomatis mouse pneumonitis (MoPn). Over a period of 6 weeks postinfection, various organs were cultured for C. trachomatis. Other infected animals were mated to assess their fertility status. No significant differences were observed between WT and KO mice in the number of animals with positive vaginal cultures, length of time of C. trachomatis shedding, or the number of C. trachomatis inclusion‐forming units (IFU) recovered from their genital tracts. Likewise, the number of animals with hydrosalpinx, and the fertility rates and the number of embryos per mouse, were similar in WT and KO mice. Cultures from the spleen, lungs, kidneys and large intestine yielded similar numbers of IFU from WT and KO mice. However, the number of C. trachomatis IFU recovered from the small intestine of KO mice was significantly higher than that recovered from the small intestine of WT mice at 2 weeks postinfection. Because MMP‐7 KO mice are deficient in active intestinal α‐defensins, the results suggest that these components play a role in regulating colonization of the gastrointestinal tract by Chlamydia. By contrast, MMP‐7 is dispensable in the progression and resolution of the genital tract infection.
Geographical affinities of the Cape flora, South Africa
Authors: Galley C. , Linder H. P. 
Published: November 2005

AbstractAim The flora characteristic of the Cape Floristic Region (CFR) is dominated by a relatively small number of clades that have been proposed as ‘Cape clades’. These clades have variously been suggested to have African or Austral affinities. Here we evaluate the support for these conflicting hypotheses. In addition, we test the hypothesis that these clades share a common time of differentiation from their geographical neighbours.Location The Cape Floristic Region, South AfricaMethods We use both published and unpublished phylogenetic information to investigate the geographical sister areas of the Cape clades as well as the timing and the direction of biogeographical disjunctions.Results Almost half of the Cape clades for which unambiguous sister areas could be established show a trans‐Indian Ocean disjunction. The earliest trans‐Indian Ocean disjunction dates from 80 Ma. Other disjunctions date from various times in the Cenozoic, and we suggest that the process of recruiting lineages into the Cape flora might be ongoing. Relatively few Cape clades show a sister relationship with South America and tropical Africa, despite their relative geographical proximity. Numerous Cape clades contain species also found on tropical African mountains; in all cases tested, these species are shown to be embedded within the Cape clades. While many Cape clades show a relationship with the Eurasian temperate flora, this is complicated by their presence in tropical Africa. The single case study addressing this to date suggests that the Cape clade is nested within a European grade.Main conclusions Although many Cape clades show Austral rather than African relationships, there are numerous other patterns suggestive of a cosmopolitan flora. This spatial variation is echoed in the temporal data, from which, although there is wide variance around the dates of disjunctions, it is clear the Cape flora has been assembled over a long time period. There is no simple hypothesis that can account for the geographical sources of the currently distinctive Cape flora. The phylogenetic positions of Afromontane members of Cape clades suggest a history of dispersal from the CFR, rather than the reverse.
The outcomes of an intervention study to reduce the barriers experienced by people with intellectual disabilities accessing primary health care services
Authors: Melville C. A. , Cooper S.‐A. , Morrison J. , Finlayson J. , Allan L. , Robinson N. , Burns E. , Martin G. 
Published: November 2005

AbstractBackground  People with intellectual disabilities (IDs) experience significant health inequalities compared with the general population. The barriers people with IDs experience in accessing services contribute to these health inequalities. Professionals’ significant unmet training needs are an important barrier to people with IDs accessing appropriate services to meet their health needs.Method  A three group, pre‐ and post‐intervention design was used to test the hypothesis that a training intervention for primary health care professionals would increase the knowledge and self‐efficacy of participants. The intervention had two components – a written training pack and a 3‐hour face‐to‐face training event. One group received the training pack and attended the training event, a second group received the training pack only, and a third group did not participate in the training intervention. Research measures were taken prior to the intervention and 3 months after the intervention. Statistical comparisons were made between the three groups.Results  The participants in the training intervention reported that it had a positive impact upon their knowledge, skills and clinical practice. As a result of the intervention, 35 (81.4%) respondents agreed that they were more able to meet the needs of their clients with IDs, and 33 (66.6%) reported that they had made changes to their clinical practice. The research demonstrated that the intervention produced a statistically significant increase in the knowledge of participants (F = 5.6, P = 0.005), compared with the group that did not participate in the intervention. The self‐efficacy of the participants that received both components of the intervention was significantly greater than the group that did not participate in the training (t = 2.079, P = 0.04). Participation in the two components of the training intervention was associated with significantly greater change in knowledge and self‐efficacy than those receiving the training pack alone.Conclusion  This intervention was effective in addressing the measured training needs of primary health care professionals. Future research should directly evaluate the positive benefits of interventions on the lives of people with IDs.
A measure of food seeking in individuals with Prader–Willi syndrome
Authors: Young J. , Zarcone J. , Holsen L. , Anderson M. C. , Hall S. , Richman D. , Butler M. G. , Thompson T. 
Published: November 2005

AbstractBackground  Individuals with Prader–Willi syndrome (PWS), a chromosome 15 genetic disorder, often have a significant preoccupation with food and problem behaviour related to food seeking is often prevalent.Methods  In the present study, we compared how individuals with PWS responded on a survey regarding the acceptability of food in various locations that varied according to degree of appropriateness for human consumption (e.g. food on a plate, food in a garbage can). For a subgroup of participants, we observed how they actually responded when placed in a room with food items placed in the same locations depicted in the survey. In the first part of the study, three groups (25 typically developing individuals, 7 individuals with intellectual disability (ID), and 19 individuals with PWS) responded to a visual survey to determine the degree of acceptability of food items in various locations (e.g. on a table near a hairbrush, on the floor behind a toy box, in a trash can). In the second part of the study, these food items (popcorn, jelly beans) were placed in the 12 locations described above. Nine individuals diagnosed with PWS (deletion type) and three individuals with ID were given some break time in the room for 15 min. The amount of food consumed, the time spent food seeking, and time spent interacting with materials were measured.Results  Results of the survey indicated that the PWS group differed significantly with regard to how they responded on the survey from the typically developing group, but did not differ significantly from the ID group. Results of the food seeking observations indicated that only three individuals with PWS ate a significant number of items. The three individuals did not differ from the rest of the group according to IQ or compulsivity score; however, they had significantly lower body mass index (BMI) scores and were younger than the other participants.Conclusions  The findings from the survey indicate that individuals with PWS are able to discriminate the appropriateness of eating items in more or less contaminated areas; however, the amount of time spent seeking food and the amount of food covertly consumed appeared to depend more directly on age and BMI.
Preferences in individuals with Angelman syndrome assessed by a modified Choice Assessment Scale
Authors: Didden R. , Korzilius H. , Kamphuis A. , Sturmey P. , Lancioni G. , Curfs L. M. G. 
Published: November 2005

AbstractBackground  Individuals with Angelman syndrome (AS) seem to have a strong preference for water‐related items. Until present, preference assessment in AS has not been reported.Methods  An adapted Dutch version of the Choice Assessment Scale (CAS) was administered by parents and other caregivers to 105 individuals with AS. The CAS was adapted by adding several items related to water and by adding a sub‐scale describing activities and materials that individuals may avoid or escape.Results  The five sub‐scales and total scale of the modified CAS had good internal consistency. Water‐related items were more often scored as preferred than non‐water‐related items. No associations were found between sub‐scale and total scale scores and demographic characteristics (e.g. genetic subtype, age).Conclusions  This study shows that people with AS often have strong preferences for water‐related items. The modified CAS is a reliable and sensitive instrument to assess client preferences.
QT interval prolongation and arrhythmia: an unbreakable connection?
Authors: ANDERSON M. E. 
Published: November 2005

Abstract.QT interval prolongation is incontrovertibly linked to increased risk of arrhythmias but, paradoxically, QT interval prolongation can also be an effective antiarrhythmic strategy and is in fact the goal of class III antiarrhythmic drugs. This discussion examines the cellular effects of QT interval prolongation and proposes that calmodulin kinase II (CaMKII) is a specific cellular proarrhythmic signal that is activated downstream to QT interval prolongation. Inhibition of CaMKII can prevent cellular arrhythmia surrogates andin vivoarrhythmias linked to excessive action potential prolongation, suggesting that QT interval prolongation alone does not fully account for proarrhythmia. This reasoning points to the conclusion that QT interval modulation and prolongation not only grades cellular Ca2+entry for cardiac contraction but also has the potential to recruit Ca2+‐activated signalling molecules. CaMKII is one of these molecules and CaMKII activity is at least partially responsible for the proarrhythmic consequences of excessive QT interval prolongation.
The short QT syndrome as a paradigm to understand the role of potassium channels in ventricular fibrillation
Authors: CERRONE M. , NOUJAIM S. , JALIFE J. 
Published: November 2005

Abstract.The recently discovered hereditary channelopathy, the Short QT Syndrome (SQTS), is an important advance in clinical and molecular cardiology that has opened new doors for investigating the manner in which alterations in excitability and action potential morphology may facilitate the occurrence of ventricular fibrillation. In this brief review we address the molecular and genetic features of SQTS in which specific mutations in one of three different potassium channels involved in cardiac repolarization substantially increase the risk of life‐threatening tachyarrhythmias. We then summarize new knowledge on the mechanism of wavebreak, which is the hallmark of reentry initiation, and on the role of potassium channels in the ionic mechanisms underlying cardiac excitation and its frequency dependence. The article argues for a detailed understanding of the ionic mechanisms that promote wavebreaks and stable rotors as an essential tool for successful anti‐arrhythmic therapy in SQTS and other diseases leading to sudden cardiac death.
The congenital long QT syndromes from genotype to phenotype: clinical implications
Authors: SCHWARTZ PETER J. 
Published: November 2005

Abstract.The long QT syndrome (LQTS) is a genetic disorder responsible for many sudden deaths before age 20. The identification of several LQTS genes, all encoding cardiac ion channels, has had a major impact on the management strategy for both patients and family members. Genotype‐guided therapy allows more effective individually tailored therapy. Therapeutic options, including β‐blockers, left cardiac sympathetic denervation, and implantable defibrillators are discussed for patients of known and of unknown genotype. The recent identification of modifier genes which amplify the effect of an LQTS mutation may change the approach to risk stratification.
Fracture risk in patients treated with loop diuretics
Authors: REJNMARK L. , VESTERGAARD P. , MOSEKILDE L. 
Published: November 2005

Abstract.Background.  Loop diuretics (LD) increase renal calcium excretion. Discrepant results on associations between LD and fracture risk have been reported.Objective.  To assess the fracture risk in users of LD.Design and subjects.  A population‐based pharmaco‐epidemiological case–control design with fracture in year 2000 as outcome and use of LD during the previous 5 years as exposure variable. We used nationwide computerized registers to assess individual use of LD and related these data to individual fracture data and information on potential confounders. We compared 64 699 cases aged 40 years or more who sustained a fracture during year 2000 with 194 111 age‐ and gender‐matched controls.Results.  A total of 44 001 subjects used LD. Ever use of LD was associated with a crude 51% (OR 1.51; 95% CI 1.48–1.55) increased risk of any fracture and a 72% (OR 1.72; 95% CI 1.64–1.81) increased risk of hip fracture. The risk estimates were reduced after confounder adjustment, i.e. adjusted risk of any fracture was increased by 4% (OR 1.04; 95% CI 1.01–1.07) and risk of hip fracture by 16% (OR 1.16; 95% CI 1.10–1.23). In current users, a tendency towards a decreased fracture risk with increased dose was observed, whereas in former users risk of fracture increased with increased dose. Use of furosemide was associated with higher risk estimates than use of bumetanide.Conclusion.  Treatment with LD affects fracture risk. Special attention should be paid to patients in whom treatment with LD is initiated or stopped, as they may be at an increased risk of fracture.