bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functional effects of spinocerebellar ataxia type 13 mutations are conserved in zebrafish Kv3.3 channels
Authors: Mock Allan F , Richardson Jessica L , Hsieh Jui-Yi , Rinetti Gina , Papazian Diane M 
Published: August 2010

Abstract

Background
The zebrafish has been suggested as a model system for studying human diseases that affect nervous system function and motor output. However, few of the ion channels that control neuronal activity in zebrafish have been characterized. Here, we have identified zebrafish orthologs of voltage-dependent Kv3 (KCNC) K+ channels. Kv3 channels have specialized gating properties that facilitate high-frequency, repetitive firing in fast-spiking neurons. Mutations in human Kv3.3 cause spinocerebellar ataxia type 13 (SCA13), an autosomal dominant genetic disease that exists in distinct neurodevelopmental and neurodegenerative forms. To assess the potential usefulness of the zebrafish as a model system for SCA13, we have characterized the functional properties of zebrafish Kv3.3 channels with and without mutations analogous to those that cause SCA13.

Results
The zebrafish genome (release Zv8) contains six Kv3 family members including two Kv3.1 genes (kcnc1a and kcnc1b), one Kv3.2 gene (kcnc2), two Kv3.3 genes (kcnc3a and kcnc3b), and one Kv3.4 gene (kcnc4). Both Kv3.3 genes are expressed during early development. Zebrafish Kv3.3 channels exhibit strong functional and structural homology with mammalian Kv3.3 channels. Zebrafish Kv3.3 activates over a depolarized voltage range and deactivates rapidly. An amino-terminal extension mediates fast, N-type inactivation. The kcnc3a gene is alternatively spliced, generating variant carboxyl-terminal sequences. The R335H mutation in the S4 transmembrane segment, analogous to the SCA13 mutation R420H, eliminates functional expression. When co-expressed with wild type, R335H subunits suppress Kv3.3 activity by a dominant negative mechanism. The F363L mutation in the S5 transmembrane segment, analogous to the SCA13 mutation F448L, alters channel gating. F363L shifts the voltage range for activation in the hyperpolarized direction and dramatically slows deactivation.

Conclusions
The functional properties of zebrafish Kv3.3 channels are consistent with a role in facilitating fast, repetitive firing of action potentials in neurons. The functional effects of SCA13 mutations are well conserved between human and zebrafish Kv3.3 channels. The high degree of homology between human and zebrafish Kv3.3 channels suggests that the zebrafish will be a useful model system for studying pathogenic mechanisms in SCA13.
A population-based survey of the epidemiology of symptom-defined gastroesophageal reflux disease: the Systematic Investigation of Gastrointestinal Diseases in China
Authors: He Jia , Ma Xiuqiang , Zhao Yanfang , Wang Rui , Yan Xiaoyan , Yan Hong , Yin Ping , Kang Xiaoping , Fang Jiqian , Hao Yuantao , Li Qiang , Dent John , Sung Joseph JY , Zou Duowu , Wallander Mari-Ann , Johansson Saga , Liu Wenbin , Li Zhaoshen 
Published: August 2010

AbstractBackgroundThe epidemiology of gastroesophageal reflux disease (GERD) has yet to be investigated using the symptomatic threshold criteria recommended by the Montreal Definition. This study aimed to determine the prevalence of symptom-defined GERD across five regions of China, and to investigate variables associated with GERD.MethodsA representative sample of 18 000 adults (aged 18-80 years) were selected equally from rural and urban areas in each region (n = 1800). According to the Montreal Definition, GERD is present when mild symptoms of heartburn and/or regurgitation occur on ≥2 days a week, or moderate-to-severe symptoms of heartburn and/or regurgitation occur on ≥1 day a week.ResultsIn total, 16 091 participants completed the survey (response rate: 89.4%) and 16 078 responses were suitable for analysis. Applying the Montreal criteria, the prevalence of symptom-defined GERD was 3.1% and varied significantly (p< 0.001) among the five regions (from 1.7% in Guangzhou to 5.1% in Wuhan) and between rural and urban populations (3.8% vs 2.4%). Factors significantly associated with GERD included living in a rural area and a family history of gastrointestinal diseases.ConclusionsThis population-based survey found that the prevalence of symptom-defined GERD in China was 3.1%, which is lower than that found in Western countries.
Downregulation of metastasis suppressor 1(MTSS1) is associated with nodal metastasis and poor outcome in Chinese patients with gastric cancer
Authors: Liu Ke , Wang Gefang , Ding Houzhong , Chen Ying , Yu Guanzhen , Wang Jiejun 
Published: August 2010

Abstract

Background
The putative tumor metastasis suppressor 1(MTSS1) is an actin-binding scaffold protein that has been implicated to play an important role in carcinogenesis and cancer metastasis, yet its role in the development of gastric cancer has not been well illustrated. In this study, we detected MTSS1 expression and explored its clinical significance in gastric cancer.

Methods
Immunohistochemistry was performed using tissue microarrays containing gastric adenocarcinoma specimens from 1,072 Chinese patients with normal adjacent mucosa, primary gastric cancer and lymph node (LN) metastasis and specific antibody against MTSS1. MTSS1 mRNA and protein expression were detected by reverse transcription-polymerase chain reaction and Western blotting. The clinical follow-up was done in the 669 patients living in Shanghai that was chose from the 1072 cases.

Results
Complete loss of MTSS1 expression was observed in 751 cases (70.1%) of the 1,072 primary tumors and 103 (88%) of 117 nodal metastases; and loss of MTSS1 expression was significantly associated with poorly differentiated tumors, large tumor size, deep invasion level, the presence of nodal metastases and advanced disease stage. Moreover, multivariate analysis demonstrated that loss of MTSS1 expression correlated significantly with poor survival rates (RR = 0.194, 95% CI = 0.144-0.261, P < 0.001).

Conclusions
MTSS1 expression decreased significantly as gastric cancer progressed and metastasized, suggesting MTSS1 may serve as a useful biomarker for the prediction of outcome of gastric cancer.
Analysis of genetic copy number changes in cervical disease progression
Authors: Policht Frank A , Song Minghao , Sitailo Svetlana , O'Hare Anna , Ashfaq Raheela , Muller Carolyn Y , Morrison Larry E , King Walter , Sokolova Irina A 
Published: August 2010

Abstract

Background
Cervical dysplasia and tumorigenesis have been linked with numerous chromosomal aberrations. The goal of this study was to evaluate 35 genomic regions associated with cervical disease and to select those which were found to have the highest frequency of aberration for use as probes in fluorescent in-situ hybridization.

Methods
The frequency of gains and losses using fluorescence in-situ hybridization were assessed in these 35 regions on 30 paraffin-embedded cervical biopsy specimens. Based on this assessment, 6 candidate fluorescently labeled probes (8q24, Xp22, 20q13, 3p14, 3q26, CEP15) were selected for additional testing on a set of 106 cervical biopsy specimens diagnosed as Normal, CIN1, CIN2, CIN3, and SCC. The data were analyzed on the basis of signal mean, % change of signal mean between histological categories, and % positivity.

Results
The study revealed that the chromosomal regions with the highest frequency of copy number gains and highest combined sensitivity and specificity in high-grade cervical disease were 8q24 and 3q26. The cytological application of these two probes was then evaluated on 118 ThinPrep™ samples diagnosed as Normal, ASCUS, LSIL, HSIL and Cancer to determine utility as a tool for less invasive screening. Using gains of either 8q24 or 3q26 as a positivity criterion yielded specificity (Normal +LSIL+ASCUS) of 81.0% and sensitivity (HSIL+Cancer) of 92.3% based on a threshold of 4 positive cells.

Conclusions
The application of a FISH assay comprised of chromosomal probes 8q24 and 3q26 to cervical cytology specimens confirms the positive correlation between increasing dysplasia and copy gains and shows promise as a marker in cervical disease progression.
Incidence of type 2 diabetes in Aboriginal Australians: an 11-year prospective cohort study
Authors: Wang Zhiqiang , Hoy Wendy E , Si Damin 
Published: August 2010

Abstract

Background
Diabetes is an important contributor to the health inequity between Aboriginal and non-Aboriginal Australians. This study aims to estimate incidence rates of diabetes and to assess its associations with impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) among Aboriginal participants in a remote community.

Methods
Six hundred and eighty six (686) Aboriginal Australians aged 20 to 74 years free from diabetes at baseline were followed for a median of 11 years. During the follow-up period, new diabetes cases were identified through hospital records. Cox proportional hazards models were used to assess relationships of the incidence rates of diabetes with IFG, IGT and body mass index (BMI).

Results
One hundred and twenty four (124) new diabetes cases were diagnosed during the follow up period. Incidence rates increased with increasing age, from 2.2 per 1000 person-years for those younger than 25 years to 39.9 per 1000 person-years for those 45-54 years. By age of 60 years, cumulative incidence rates were 49% for Aboriginal men and 70% for Aboriginal women. The rate ratio for developing diabetes in the presence of either IFG or IGT at baseline was 2.2 (95% CI: 1.5, 3.3), adjusting for age, sex and BMI. Rate ratios for developing diabetes were 2.2 (95% CI: 1.4, 3.5) for people who were overweight and 4.7 (95% CI: 3.0, 7.4) for people who were obese at baseline, with adjustment of age, sex and the presence of IFG/IGT.

Conclusions
Diabetes incidence rates are high in Aboriginal people. The lifetime risk of developing diabetes among Aboriginal men is one in two, and among Aboriginal women is two in three. Baseline IFG, IGT and obesity are important predictors of diabetes.
The correlation of osteoporosis to clinical features: a study of 4382 Female Cases of a Hospital Cohort with musculoskeletal symptoms in Southwest China
Authors: Li Shasha , He Hongchen , Ding Mingfu , He Chengqi 
Published: August 2010

Abstract

Background
By analyzing the clinical features and risk factors in female patients with musculoskeletal symptoms of Southwest China, this report presents the initial analysis of characteristics in this region and compared with international evaluative criteria.

Methods
Diagnosis of osteoporosis (OP) was made in female hospital patients age ≥ 18 years admitted from January 1998 to December 2008 according to WHO definition. Case data were analyzed by symptoms, age, disease course and risk factors to reveal correlation with diagnosis of OP. Logistic regression was used to identify the risks of osteoporosis.

Results
A total of 4382 patients were included in the analysis of the baseline characteristics, among which 1455 in the OP group and 2927 in the non-OP group. The morbidity of OP is significantly increased in females' ≥ 50 years. Both groups had symptoms related to pain and numbness; no significant difference was found in reported upper and lower back pain, or leg pain between two groups (p > 0.05). Neck, shoulder and arm pain, leg and arm numbness were more common in the non-osteoporosis group (p < 0.05, OR < 1, and upper limit of 95% CI of OR < 1). Hypertension, diabetes, hyperostosis were major risk factors for the patients with OP. The most common lifestyle-related risk factors for osteoporosis were smoking, body mass index, lack of physical activity and menopause.

Conclusions
The present study offers the first reference data of the relationship between epidemiologic distribution of osteoporosis and associated factors in adults Chinese women. These findings provide a theoretical basis for its prevention and treatment in developing country.
Effect of candesartan monotherapy on lipid metabolism in patients with hypertension: a retrospective longitudinal survey using data from electronic medical records
Authors: Nishida Yayoi , Takahashi Yasuo , Nakayama Tomohiro , Soma Masayoshi , Kitamura Noboru , Asai Satoshi 
Published: August 2010

Abstract

Background
Studies focusing on the add-on effects of angiotensin II type 1 receptor blockers (ARBs) other than their antihypertensive effect are receiving attention. However, the effects of prolonged administration of ARBs on lipid metabolism in clinical cases are unclear. Our aims were to survey the changes in plasma lipid profile in patients with hypertension over a one-year period, and to examine the correlations between these values and the time after the start of ARB monotherapy with candesartan.

Methods
We carried out candesartan monotherapy in patients with mild to moderate hypertension and examined the longitudinal changes in plasma lipid profile. Data from 405 patients for triglyceride (TG), 440 for total cholesterol (TC), 313 for high density lipoprotein cholesterol (HDL-C) and 304 for low density lipoprotein cholesterol (LDL-C) were obtained from the electronic medical records (EMRs) in the Clinical Data Warehouse (CDW) of Nihon University School of Medicine (NUSM). The inverse probability of treatment weighting (IPTW) method (calculated from the inverse of the propensity score) was used to balance the covariates and reduce bias in each treatment duration. Linear mixed effects models were used to analyse the relationship between these longitudinal data of blood examinations and covariates of patient sex, age, diagnosis of diabetes mellitus (DM) and duration of candesartan monotherapy.

Results
Plasma HDL-C level was associated with sex, duration of treatment, and interaction of sex and treatment duration, but not with age or diagnosis of DM. HDL-C level was significantly decreased during the 6~9 months period (p = 0.0218) compared with baseline. TG and TC levels were associated with sex, but not with age, diagnosis of DM or treatment duration. LDL-C level was not associated with any covariate. Analysis of the subjects divided by sex revealed a decrease in HDL-C in female subjects (during the 6~9 months period: p = 0.0054), but not in male subjects.

Conclusions
Our study revealed that administration of candesartan slightly decreased HDL-C in female subjects. However, TG, TC and LDL-C levels were not influenced by candesartan monotherapy. Candesartan may be safely used for patients with hypertension with respect to lipid metabolism, because the effect of candesartan on lipids may be small.
Deoxysphingoid bases as plasma markers in Diabetes mellitus
Authors: Bertea Mariana , Rütti Markus F. , Othman Alaa , Marti-Jaun Jaqueline , Hersberger Martin , von Eckardstein Arnold , Hornemann Thorsten 
Published: August 2010

Abstract

Background
Sphingoid bases are formed from the precursors L-serine and palmitoyl-CoA-a reaction which is catalyzed by the serine-palmitoyltransferase (SPT). SPT metabolizes, besides palmitoyl-CoA also other acyl-CoAs but shows also variability towards the use of other amino acid substrates. The enzyme is also able to metabolize alanine, which results in the formation of an atypical deoxy-sphingoid base (DSB). This promiscuous activity is greatly increased in the case of the sensory neuropathy HSAN1, and pathologically elevated DSB levels have been identified as the cause of this disease. Clinically, HSAN1 shows a pronounced similarity to the diabetic sensory neuropathy (DSN), which is the most common chronic complication of diabetes mellitus. Since serine and alanine metabolism is functionally linked to carbohydrate metabolism by their precursors 3-phosphoglycerate and pyruvate, we were interested to see whether the levels of certain sphingoid base metabolites are altered in patients with diabetes.

Results
In a case-control study we compared plasma sphingoid base levels between healthy and diabetic individuals. DSB levels were higher in the diabetic group whereas C16 and C18 sphingoid bases were not significantly different. Plasma serine, but not alanine levels were lower in the diabetic group. A subsequent lipoprotein fractionation showed that the DSBs are primarily present in the LDL and VLDL fraction.

Conclusion
Our results suggest that DSBs are a novel category of plasma biomarkers in diabetes which reflect functional impairments of carbohydrate metabolism. Furthermore, elevated DSB levels as we see them in diabetic patients might also contribute to the progression of the diabetic sensory neuropathy, the most frequent complication of diabetes.
Psychometric validation of the Dutch translation of the quality of life in reflux and dyspepsia (QOLRAD) questionnaire in patients with gastroesophageal reflux disease
Authors: Engels Leopold GJB , Klinkenberg-Knol Elly C , Carlsson Jonas , Halling Katarina 
Published: August 2010

Abstract

Background
The Quality of Life in Reflux and Dyspepsia (QOLRAD) questionnaire is one of the best-characterized disease-specific instruments that captures health-related problems and symptom-patterns in patients with gastroesophageal reflux disease (GERD). This paper reports the psychometric validation of a Dutch translation of the QOLRAD questionnaire in gastroenterology outpatients with GERD.

Methods
Patients completed the QOLRAD questionnaire at visit 1 (baseline), visit 2 (after 2, 4 or 8 weeks of acute treatment with esomeprazole 40 mg once daily), and visit 4 (after 6 months with on-demand esomeprazole 40 mg once daily or continuous esomeprazole 20 mg once daily). Symptoms were assessed at each visit, and patient satisfaction was assessed at visits 2 and 4.

Results
Of the 1166 patients entered in the study, 97.3% had moderate or severe heartburn and 55.5% had moderate or severe regurgitation at baseline. At visit 2, symptoms of heartburn and regurgitation were mild or absent in 96.7% and 97.7%, respectively, and 95.3% of patients reported being satisfied with the treatment. The internal consistency and reliability of the QOLRAD questionnaire (range: 0.83-0.92) supported construct validity. Convergent validity was moderate to low. Known-groups validity was confirmed by a negative correlation between the QOLRAD score and clinician-assessed severity of GERD symptoms. Effect sizes (1.15-1.93) and standardized response means (1.17-1.86) showed good responsiveness to change. GERD symptoms had a negative impact on patients' lives.

Conclusions
The psychometric characteristics of the Dutch translation of the QOLRAD questionnaire were found to be satisfactory, with good reliability and responsiveness to change, although convergent validity was at best moderate.
PET-CT staging of the neck in cancers of the oropharynx: patterns of regional and retropharyngeal nodal metastasis
Authors: Tauzin Marcie , Rabalais Amy , Hagan Joseph L , Wood Charles G , Ferris Robert L , Walvekar Rohan R 
Published: August 2010

Abstract

Objective
To study the retropharyngeal lymph node status (RPLN) by pretreatment PET-CT imaging in patients with squamous cell carcinomas of the oropharynx (OPSCC). Study Design: Retrospective.

Methods
101 patients with a biopsy proven OPSCC were identified. 53 patients meeting inclusion criteria were further analyzed.

Results
The frequency of RPLN was 20.8% (11/53). Advanced T stage cancer (OR = 5.6250, 95% CI: 1.06 - 29.80, p = 0.0410) and advanced clinical N stage cancer (i.e. N2+) had higher odds (OR = 3.9773, 95% CI: 0.9628 - 16.4291) of being RPLN positive as compared to N0-1 patients.

Conclusions
Pre-treatment PET-CT can be used as a staging tool to aid in treatment planning of OPSCC, as rates of RPLN and nodal metastasis are consistent with those reported in the literature. Advanced T and N stage are associated with a greater odds ratio of being RPLN positive by PET-CT imaging.
Whole ovary immunohistochemistry for monitoring cell proliferation and ovulatory wound repair in the mouse
Authors: Singavarapu Rajasekhar , Buchinsky Natalie , Cheon Dong-Joo , Orsulic Sandra 
Published: August 2010

Abstract

Background
Ovarian surface epithelial cells are thought to be a precursor cell type for ovarian carcinoma. It has been proposed that an increased rate of ovarian surface epithelial cell proliferation during ovulatory wound repair contributes to the accumulation of genetic changes and cell transformation. The proliferation of ovarian surface epithelial cells during ovulatory wound repair has been studied primarily using immunohistochemical staining of paraffin-embedded ovary sections. However, such analyses require complex reconstruction from serially-cut ovary sections for the visualization and quantification of the cells on the ovarian surface. In order to directly visualize the proliferation and organization of the ovarian surface epithelial cells, we developed a technique for immunohistochemical staining of whole mouse ovaries. Using this method, we analyzed cell proliferation and morphologic changes in mouse ovarian surface epithelial cells during follicle growth and ovulatory wound repair.

Methods
Three-week old FVB/N female mice were superovulated by sequential administration of pregnant mare's serum gonadotropin (PMSG) and human chorionic gonadotropin (hCG). Ten hours after hCG administration, mice were given 5-bromo-2-deoxyuridine (BrdU) and euthanized two hours after BrdU administration for ovary isolation. The levels of incorporated BrdU in the ovarian surface epithelial cells were measured by staining paraffin-embedded ovary sections and whole ovaries with the BrdU antibody. Re-epithelialization of the ovarian surface after ovulatory rupture was visualized by immunohistochemical staining with E-cadherin and Keratin 8 in paraffin-embedded ovary sections and whole ovaries.

Results
We determined that active proliferation of ovarian epithelial surface cells primarily occurs during antral follicle formation and, to a lesser extent, in response to an ovulatory wound. We also demonstrated that ovarian surface epithelial cells exhibit a circular organization around the wound site

Conclusion
Whole ovary immunohistochemistry enables efficient and comprehensive three-dimensional visualization of ovarian surface epithelial cells without the need for laborious reconstruction from immunohistochemically-stained serial ovary sections.
Transcriptomic biomarkers of the response of hospitalized geriatric patients with infectious diseases
Authors: Vo Thi Kim Duy , Godard Patrice , de Saint-Hubert Marie , Morrhaye Gabriel , Swine Christian , Geenen Vincent , Martens Henri J , Debacq-Chainiaux Florence , Toussaint Olivier 
Published: August 2010

AbstractBackgroundInfectious diseases are significant causes of morbidity and mortality among elderly populations. However, the relationship between oxidative stress, immune function and inflammatory response in acute phase of the infectious disease is poorly understood.ResultsHerein the abundance of a selection of 148 transcripts involved in immunosenescence and stress response was compared in total RNA of PBMC of 28 healthy aged probands and 39 aged patients in acute phase of infectious disease (day 2-4 after hospitalization) or in convalescence phase (day 7-10). This study provides a list of 24 differentially abundant transcript species in the acute phase versus healthy aged. For instance, transcripts associated with inflammatory and anti-inflammatory reactions (TNFRSF1A, IL1R1, IL1R2, IL10RB) and with oxidative stress (HMOX1, GPX1, SOD2, PRDX6) were more abundant while those associated with T-cell functions (CD28, CD69, LCK) were less abundant in acute phase. The abundance of seven of these transcripts (CD28, CD69, LCK, CTSD, HMOX1, TNFRSF1A and PRDX6) was already known to be altered in healthy aged probands compared to healthy young ones and was further affected in aged patients in acute phase, compromising an efficient response.ConclusionThis work provides insights of the state of acute phase response to infections in elderly patients and could explain further the lack of appropriate response in the elderly compared to younger persons.