bluuebunny/crossref_metadata_2025_split huggingface dataset:
Variants of DsRed fluorescent protein: Development of a copper sensor
Authors: Eli Pharhad , Chakrabartty Avijit 
Published: September 2006

AbstractThe fluorescence quenching of drFP583 (DsRed) protein by metal ions was investigated. CuSO4 reversibly and pH dependently quenched the red emission at 583 nm of drFP583. The copper binding constant was 15 mM. Following random mutagenesis, blue‐ and red‐shifted mutants of drFP583 were generated, and their metal sensing properties were examined. Mutant gRF possessed properties similar to green fluorescent protein and had a 18 mM copper binding constant. Mutant Rmu162 had an extraordinary red‐shifted emission peak at 620 nm. A third mutant, Rmu13, had dual emission peaks at 500 nm and 583 nm and possessed the properties of a copper sensor with a binding constant of 11 mM.
Characterization of the five novel Ly‐6 superfamily members encoded in the MHC, and detection of cells expressing their potential ligands
Authors: Mallya Meera , Campbell R. Duncan , Aguado Begoña 
Published: September 2006

AbstractLymphocyte Antigen 6 (Ly‐6) superfamily members are cysteine‐rich, generally GPI‐anchored cell surface proteins, which have definite or putative immune related roles. There are 27 members of this family described so far in the human genome and 37 in the mouse. Five of them are clustered in the class III region of the human and mouse MHCs. Following computational analyses, we functionally characterized the encoded proteins by creating epitope‐tagged fusion constructs to determine molecular weight, complex formation, subcellular localization, post‐translational modifications and ligand binding. We found that all human and mouse proteins were glycosylated, and most could form part of larger complexes. Human and mouse Ly6G6c and Ly6G6d, and mouse Ly6g6e were found to be GPI‐anchored cell surface proteins, highly expressed at the leading edges of cells, on filopodia, which are normally involved in cell adhesion and migration. However, analysis of Ly6G5c and Ly6G5b indicated that they are potentially secreted proteins. Our results indicate that there are two subclusters of related Ly‐6 proteins in this region of the MHC, with Ly6G6c, Ly6G6d, and Ly6G6e forming one and Ly6G5c and Ly6G5b forming another. In addition, by FACS analysis we have found that the potential ligands for human LY6G6C, LY6G6D, and LY6G5C are expressed on K562 cells, an undifferentiated megakaryocyte cell line, indicating a potential role in hematopoietic cell differentiation. This characterization of the five MHC class III region Ly‐6 family members is of great relevance, as they represent 18% of the human Ly‐6 protein family and 50% of the secreted ones.
Three‐dimensional structure and ligand interactions of the low molecular weight protein tyrosine phosphatase from Campylobacter jejuni
Authors: Tolkatchev Dmitri , Shaykhutdinov Rustem , Xu Ping , Plamondon Josée , Watson David C. , Young N. Martin , Ni Feng 
Published: September 2006

AbstractA putative low molecular weight protein tyrosine phosphatase (LMW‐PTP) was identified in the genome sequence of the bacterial pathogen, Campylobacter jejuni. This novel gene, cj1258, has sequence homology with a distinctive class of phosphatases widely distributed among prokaryotes and eukaryotes. We report here the solution structure of Cj1258 established by high‐resolution NMR spectroscopy using NOE‐derived distance restraints, hydrogen bond data, and torsion angle restraints. The three‐dimensional structure consists of a central four‐stranded parallel β‐sheet flanked by five α‐helices, revealing an overall structural topology similar to those of the eukaryotic LMW‐PTPs, such as human HCPTP‐A, bovine BPTP, and Saccharomyces cerevisiae LTP1, and to those of the bacterial LMW‐PTPs MPtpA from Mycobacterium tuberculosis and YwlE from Bacillus subtilis. The active site of the enzyme is flexible in solution and readily adapts to the binding of ligands, such as the phosphate ion. An NMR‐based screen was carried out against a number of potential inhibitors and activators, including phosphonomethylphenylalanine, derivatives of the cinnamic acid, 2‐hydroxy‐5‐nitrobenzaldehyde, cinnamaldehyde, adenine, and hypoxanthine. Despite its bacterial origin, both the three‐dimensional structure and ligand‐binding properties of Cj1258 suggest that this novel phosphatase may have functional roles close to those of eukaryotic and mammalian tyrosine phosphatases. The three‐dimensional structure along with mapping of small‐molecule binding will be discussed in the context of developing high‐affinity inhibitors of this novel LMW‐PTP.
Four‐year evaluation of myocardial and liver iron assessed prospectively with serial MRI scans in young patients with β‐thalassaemia major: comparison between different chelation regimens
Authors: Christoforidis Athanasios , Haritandi Afroditi , Tsatra Ioanna , Tsitourides Ioannis , Karyda Stavroula , Athanassiou‐Metaxa Miranda 
Published: September 2006

AbstractThis study was conducted in order to assess myocardial and liver iron concentrations (LICs) using serial magnetic resonance imaging (MRI) scans in patients with β‐thalassaemia major, over a 4‐yr period, and consequently to compare the effectiveness of different chelation regimens. Fifty children and young adults with β‐thalassaemia major (27 boys and 23 girls) were recruited (mean age: 14.74 ± 3.67 yr). All patients underwent detailed clinical examination, electrocardiography, echocardiography, myocardial and liver MRI at the beginning of the study, 2 and 4 yr after. Additionally, serum ferritin levels were regularly measured and data regarding LICs assessed by percutaneous liver biopsy were available in 26 patients. Both myocardial and liver MRI values showed a moderate inverse correlation with age (r = −0.379, P < 0.001 and r = −0.376, P < 0.001, respectively). Liver MRI was better correlated with serum ferritin concentrations (r = −0.342, P < 0.001) than myocardial MRI (r = −0.186, P = 0.011). Liver MRI values were highly correlated with LICs derived from percutaneous liver biopsy (r = −0.863, P < 0.001), whereas myocardial MRI values did not correlate at all with measurements derived from echocardiography. Regarding iron chelation treatment, patients receiving combined therapy with deferiprone and deferoxamine (DFO) significantly reduced myocardial iron overload during the 4‐yr study period, whilst patients in monotherapy with DFO showed a significant increase in LIC.
Rapid immune reconstitution after a reduced‐intensity conditioning regimen and a CD3‐depleted haploidentical stem cell graft for paediatric refractory haematological malignancies
Authors: Chen Xiaohua , Hale Gregory A. , Barfield Raymond , Benaim Ely , Leung Wing H. , Knowles James , Horwitz Edwin M. , Woodard Paul , Kasow Kimberly , Yusuf Usman , Behm Frederick G. , Hayden Randall T. , Shurtleff Sheila A. , Turner Victoria , Srivastava Deo Kumar , Handgretinger Rupert 
Published: September 2006

SummaryThe main obstacles to successful haploidentical haematopoietic stem cell transplantation from a mismatched family member donor are delayed immune reconstitution, vulnerability to infections and severe graft‐versus‐host disease (GvHD). We designed a reduced‐intensity conditioning regimen that excluded total body irradiation and anti‐thymocyte globulin in order to expedite immune reconstitution after a CD3‐depleted haploidentical stem cell transplant. This protocol was used to treat 22 paediatric patients with refractory haematological malignancies. After transplantation, 91% of the patients achieved full donor chimaerism. They also showed rapid recovery of CD3+ T‐cells, T‐cell receptor (TCR) excision circle counts, TCRβ repertoire diversity and natural killer (NK)‐cells during the first 4 months post‐transplantation, compared with those results from a group of patients treated with a myeloablative conditioning regimen. The incidence and extent of viremia were limited and no lethal infection was seen. Only 9% of patients had grade 3 acute GvHD, while 27% patients had grade 1 and another 27% had grade 2 acute GvHD. This well‐tolerated regimen appears to accelerate immune recovery and shorten the duration of early post‐transplant immunodeficiency, thereby reducing susceptibility to viral infections. Rapid T‐cell reconstitution, retention of NK‐cells in the graft and induction of low grade GvHD may also enhance the potential anti‐cancer immune effect.
Prospective study of body size and risk for stroke amongst women below age 60
Authors: LU M. , YE W. , ADAMI H.‐O. , WEIDERPASS E. 
Published: September 2006

Abstract.The relation between obesity, particularly abdominal obesity, and risk of stroke amongst women remains unclear. In 1991–1992, a prospective study was initiated in Sweden amongst women who returned a self‐administered questionnaire. Through linkage with nation‐wide registries, 45 449 women, free of stroke at entry, were followed up until diagnosis of first incident stroke, death, or the end of follow‐up in 2002. We estimated multivariate relative risks (RRs) with 95% confidence intervals (CIs) from Cox proportional hazards regression models. A total of 170 incident stroke cases occurred during an average of 11 years of follow‐up. The RR of stroke amongst women in the highest compared with the lowest quintile was 2.4 (95% CI 1.3–4.2;Pfor trend 0.04) for waist‐to‐hip ratio, 2.5 (95% CI 1.5–4.3;Pfor trend 0.01) for waist‐to‐height ratio and 2.3 (95% CI 1.2–4.3;Pfor trend 0.02) for waist circumference. Adjustment for hypertension and diabetes attenuated these risk estimates. In contrast, birth weight, body mass index (BMI) at age 18, BMI at entry, weight change in adulthood and adult height were not significantly associated with risk of stroke. This study provides evidence that, in contrast to BMI, several different measures of abdominal obesity are strong predictors of stroke in women.
Zoonotic viral diseases and the frontier of early diagnosis, control and prevention
Authors: HEENEY J. L. 
Published: September 2006

Abstract.Public awareness of the human health risks of zoonotic infections has grown in recent years. Currently, concern of H5N1 flu transmission from migratory bird populations has increased with foci of fatal human cases. This comes on the heels of other major zoonotic viral epidemics in the last decade. These include other acute emerging or re‐emerging viral diseases such as severe acute respiratory syndrome (SARS), West‐Nile virus, Ebola virus, monkeypox, as well as the more inapparent insidious slow viral and prion diseases. Virus infections with zoonotic potential can become serious killers once they are able to establish the necessary adaptations for efficient human‐to‐human transmission under circumstances sufficient to reach epidemic proportions. The monitoring and early diagnosis of these potential risks are overlapping frontiers of human and veterinary medicine. Here, current viral zoonotics and evolving threats are reviewed.
Prevalence of Yersinia enterocolitica in Goat Herds from Northern Germany
Authors: Arnold T. , Neubauer H. , Ganter M. , Nikolaou K. , Roesler U. , Truyen U. , Hensel A. 
Published: September 2006

SummaryThe prevalence of human pathogenic Yersinia enterocolitica isolates in livestock farming is of paramount interest. Raw goat milk has been proposed as a source of human yersiniosis; however, no data on the prevalence of human strains of Y. enterocolitica in goat herds are available. Therefore, fecal samples (n = 575) were collected from 24 goat herds from Lower Saxony, northern Germany. Pre‐enrichment in peptone, sorbitol and bile salts broth was followed by plating on cefsuloidin irgasan novobiocin agar. Yersinia enterocolitica was isolated from 17 (3%) samples of five (21%) goat herds. All isolates were biovar 1A, but represented various serovars. PCR assays targeting Yersinia adhesin (yad) gene and the yopT gene, both associated with pathogenicity, produced no amplification products. Therefore, the isolates can be regarded as opportunistic apathogenic bacteria. Consequently, milk, cheese or meat from goats should not be considered as an important source for human yersiniosis.
Establishment of A Competitive ELISA (cELISA) System for the Detection of Influenza A Virus Nucleoprotein Antibodies and its Application to Field Sera from Different Species
Authors: Starick E. , Werner O. , Schirrmeier H. , Köllner B. , Riebe R. , Mundt E. 
Published: September 2006

SummaryA recombinant baculovirus (RBV) encoding the nucleoprotein (NP) of avian influenza virus (AIV) was generated and the appropriate protein was expressed in Sf9 cells. Purified recombinant NP and the NP‐specific monoclonal antibody HB65 were used to establish a competitive ELISA (cELISA) system for the detection of NP‐specific antibodies in sera of ducks, geese and wild birds. Tests to evaluate this method were carried out using sera of ducks experimentally infected with AIV, pre‐immune duck and chicken sera, and poultry field sera, which tested negative in the haemagglutination inhibition (HI) assay, and field sera of several poultry species experimentally infected with other viruses. The evaluation of the test demonstrated a high sensitivity and specificity of this method. Tests carried out using field sera of duck and goose flocks revealed widely corresponding results obtained by HI assay and cELISA indicating that this test is applicable for flock diagnosis. Differing results were obtained for individual samples. It can be assumed that for the most part this was because of a better recognition of the conserved NP antigen by serum antibodies, although some results remained unclear.
Irritable bowel syndrome in the 21st century: Perspectives from Asia or South‐east Asia
Authors: Chang Full‐Young , Lu Ching‐Liang 
Published: September 2006

AbstractAsian irritable bowel syndrome (IBS) studies not only confirm the truth of this functional disorder but also describe the current disease situation of this continent, with its variable socioeconomic backgrounds. Most Asian community IBS prevalence is within 5–10%, regardless of gender or ethnic character. As well as meeting the main Rome II criteria, Asian IBS subjects also have many minor symptoms. Thus this recommendation remains useful to diagnose Asian IBS. Also, female patients commonly express constipation‐predominant (C‐) symptoms. Extra‐colonic symptoms are common in Asia, for example dyspepsia, insomnia and irritable urinary bladder. Asian IBS subjects do experience psychological disturbances including anxiety, depression, agoraphobia and neuroticism. Accordingly, their quality of life is poor and there is absenteeism leading to excessive physician visits. Abnormal gut motor and sensory functions have been indicated among the Asian IBS subjects. Now, there is evidence of altered colonic neuroimmune function leading to gut hypersensitivity and dysmotility. An Asia–Pacific trial also confirmed tegaserod efficacy on female C‐IBS subjects. More than 90% of nurses have very limited IBS knowledge, and are unable even to explain it clearly. In conclusion, Western recommended criteria clearly diagnose Asian IBS and many factors are mutual leading to IBS. Current IBS treatments remain useful but additional reeducation for medical professionals appears to be needed.
Changes of soluble CD26 and CD30 levels correlate with response to interferon plus ribavirin therapy in patients with chronic hepatitis C
Authors: Yang Sheng‐Shun , Fu Lin‐Shien , Chang Chi‐Sen , Yeh Hong‐Zen , Chen Gran‐Hum , Kao Jia‐Horng 
Published: September 2006

AbstractBackground: Clearance of hepatitis C virus (HCV) is attributed to host cellular immune responses, in which T helper cells play a critical role. The purpose of the present paper was therefore to study the serial changes of serum soluble markers released from T helper 1 (Th1) and 2 (Th2) and their correlations with treatment responses in chronic hepatitis C patients receiving interferon‐α plus ribavirin for 24 weeks.Methods: Serum markers (soluble CD26 and CD30 levels) of T helper cells were quantified before and 6 months after combination therapy in 33 chronic hepatitis C patients and in 20 healthy controls.Results: Compared to healthy controls, chronic hepatitis C patients had significantly lower serum soluble CD26 levels before (140.4 ± 63.9 ng/mLvs200.6 ± 60.3 ng/mL,P < 0.0001) and after (115.9 ± 32.9 ng/mLvs200.6 ± 60.3 ng/mL,P < 0.0001) combination therapy. The level was even lower in those with non‐sustained virologic response (non‐SVR; 139.0 ± 50.9 ng/mLvs117.7 ± 40.3 ng/mL,P = 0.039). In contrast, soluble CD30 levels at 6 months after combination therapy were significantly lower in patients with SVR than those with non‐SVR (6.4 ± 3.5 U/mLvs10.4 ± 5.4 U/mL,P = 0.021).Conclusion: Chronic hepatitis C patients have a weak Th1 response as reflected by lower soluble CD26 levels and the levels are even lower in non‐sustained responders. In sharp contrast, downregulation of Th2 response with serial changes of soluble CD30 level is associated with successful treatment of HCV infection.
Tumor necrosis factor‐α haplotype is strongly associated with bone mineral density in patients with Crohn's disease
Authors: Lee Naomi , Fowler Elizabeth , Mason Susan , Lincoln Douglas , Taaffe Dennis R , Radford‐Smith Graham 
Published: September 2006

AbstractBackground and Aim:  There is limited consensus on the major variables that determine bone integrity and bone loss in patients with Crohn's disease. Twin and family studies in the general population indicate that up to 85% of variance in bone mineral density is inherited. The aim was to determine the prevalence of bone loss and both molecular and clinical risk factors for bone loss in a large Crohn's disease population.Methods:  This was a cross‐sectional study of 304 patients with Crohn's disease attending the Inflammatory Bowel Disease unit at Royal Brisbane and Women's Hospital, Queensland. The results of bone density testing were ascertained directly and by a mailed questionnaire. Bone mineral density data were combined with clinical information and correlated with single nucleotide polymorphisms within the tumor necrosis factor‐α (TNF‐α), interleukin‐10, and NOD2/CARD15 genes.Results:  Of 304 Crohn's disease patients, 101 had undergone previous bone density testing. Forty‐five patients (45%) had been diagnosed with osteopenia and 18 (18%) were osteoporotic. After multivariate analysis, both the TNF‐α GT haplotype and the −857 CC genotype showed strong associations with bone mineral density overall (P = 0.003 and P = 0.002, respectively). Body mass index (P = 0.01) and previous bowel resection in female patients (P = 0.03) were predictive of a higher spine bone density, while body mass index (P = 0.003) and the effect of years since first bowel resection (P = 0.02) remained independent predictors of proximal femur bone mineral density. There were no other significant associations observed.Conclusions:  This study has identified a novel protective association between a TNF‐α haplotype and bone mineral density in Crohn's disease. It confirms the important influence of body mass index and intestinal resection on bone loss in this population.
INFLUENCE OF TRAINING ON THE FAMILY
Authors: Miller Francis J. , Miller Cheryl A. , Fox Adrian M. , Craig Giles L. , Watters David A. K. 
Published: September 2006

Background:  There is currently a shortage of surgeons working in rural Australia. This may be due to partner dissatisfaction with rural placements during training.Methods:  A questionnaire encompassing logistic, financial and emotional aspects of peripheral placements was distributed to trainees and their partners. A similar questionnaire was also distributed to 25 rural surgical consultants.Results:  Seventy‐four per cent of trainees were either married or in long‐term relationships. A further 24% had children. The average number of residential moves per year of training was 0.74. Respondents reported difficulties that included accommodation suitability, general practitioner availability, financial burden and finding amenities such as school and crèches. Many (66%) partners had experienced high levels of isolation or loneliness, whereas some reported the development of a stress‐related disorder, depression or anxiety. Most respondents indicated that their partner would influence their decision to work in a given location. Furthermore, 20% of consultant surgeons had either moved town or had seriously considered moving town because of their spouse or children’s dissatisfaction.Conclusion:  Training in peripheral locations causes significant stress to the trainee and their families. These experiences dissuade trainees from working in rural locations as consultants.
National Health Service Corps Staffing and the Growth of the Local Rural Non‐NHSC Primary Care Physician Workforce
Authors: Pathman Donald E. , Fryer George E. , Phillips Robert L. , Smucny John , Miyoshi Thomas , Green Larry A. 
Published: September 2006

ABSTRACT:
Context: Beyond providing temporary staffing, National Health Service Corps (NHSC) clinicians are believed by some observers to contribute to the long‐term growth of the non‐NHSC physician workforce of the communities where they serve; others worry that NHSC clinicians compete with and impede the supply of other local physicians. Purpose: To assess long‐term changes in the non‐NHSC primary care physician workforce of rural underserved counties that have received NHSC staffing support relative to workforce changes in underserved counties without NHSC support. Methods: Using data from the American Medical Association and NHSC, we compared changes from 1981 to 2001 in non‐NHSC primary care physician to population ratios in 2 subsets of rural whole‐county health professional shortage areas: (1) 141 counties staffed by NHSC physicians, nurse practitioners, and/or physician assistants during the early 1980s and for many of the years since and (2) all 142 rural health professional shortage area counties that had no NHSC clinicians from 1979 through 2001. Findings: From 1981 to 2001, counties staffed by NHSC clinicians experienced a mean increase of 1.4 non‐NHSC primary care physicians per 10,000 population, compared to a smaller, 0.57 mean increase in counties without NHSC clinicians. The finding of greater non‐NHSC primary care physician to population mean ratio increase in NHSC‐supported counties remained significant after adjusting for baseline county demographics and health care resources (P < .001). The estimated number of “extra” non‐NHSC physicians in NHSC‐supported counties in 2001 attributable to the NHSC was 294 additional physicians for the 141 supported counties, or 2 extra physicians, on average, for each NHSC‐supported county. Over the 20 years, more NHSC‐supported counties saw their non‐NHSC primary care workforces grow to more than 1 physician per 3,500 persons, but no more NHSC‐supported than nonsupported counties lost their health professional shortage area designations.Conclusions: These data suggest that the NHSC contributed positively to the non‐NHSC primary care physician workforce in the rural underserved counties where its clinicians worked during the 1980s and 1990s.