bluuebunny/crossref_metadata_2025_split huggingface dataset:
A six-generation Chinese family in haplogroup B4C1C exhibits high penetrance of 1555A > G-induced hearing Loss
Authors: Bai Yan , Wang Zhengmin , Dai Wenjia , Li Qingzhong , Chen Guoling , Cong Ning , Guan Minxin , Li Huawei 
Published: September 2010

Abstract

Background
The 1555A > G mutation is the most common cause of aminoglycoside-induced and non-syndromic deafness. However, the variable clinical phenotype and incomplete penetrance of A1555G-induced hearing loss complicate our understanding of this mutation. Environmental factors, nuclear genes, mitochondrial haplotypes/variants and a possible threshold effect have been reported to may be involved in its manifestation.

Methods
Here, we performed a clinical, molecular, genetic and phylogenic analysis in a six-generation Chinese family.

Results
A clinical evaluation revealed that affected individuals without aminoglycoside exposure developed hearing loss extending gradually from 12000 Hz to 8000 Hz and then to 4000 Hz. Using pyrosequencing, we detected an identical homoplasmic 1555A > G mutation in all individuals except one. We did not find any correlation between the mutation load and the severity of hearing loss. T123N coexisted with the 1555A > G mutation in six affected subjects in our pedigree. Analysis of the complete mtDNA genome of this family revealed that this family belonged to haplotype B4C1C and exhibited high penetrance. Upon the inclusion of subjects that had been exposed to aminoglycosides, the penetrance of the hearing loss was 63.6%.; without exposure to aminoglycosides, it was 51.5%. This pedigree and another reported Chinese pedigree share the same haplotype (B4C1C) and lack functionally significant mitochondrial tRNA variants, but nevertheless they exhibit a different penetrance of hearing loss.

Conclusions
Our results imply that the factors responsible for the higher penetrance and variable expression of the deafness associated with the 1555A > G mutation in this pedigree may not be mtDNA haplotype/variants, but rather nuclear genes and/or aminoglycosides.
Variant rs9939609 in the FTO gene is associated with body mass index among Chinese children
Authors: Fang Hongyun , Li Yanping , Du Songming , Hu Xiaoqi , Zhang Qian , Liu Ailing , Ma Guansheng 
Published: September 2010

Abstract

Background
Fat-mass and obesity-associated (FTO) gene is a gene located in chromosome region 16q12.2. Genetic variants in FTO are associated with the obesity phenotype in European and Hispanic populations. However, this association still remains controversial in Asian population. We aimed to test the association of FTO genetic variants with obesity and obesity-related metabolic traits among children living in Beijing, China.

Methods
We genotyped FTO variants rs9939609 in 670 children (332 girls and 338 boys) aged 8-11 years living in Beijing, and analyzed its association with obesity and obesity-related metabolic traits. Overweight and obesity were defined by age- and sex-specific BMI reference for Chinese children. Obesity-related metabolic traits included fasting plasma glucose, lipid profiles, leptin, ghrelin, adiponectin and blood pressures.

Results
The frequency of rs9939609 A allele was 12.2%, which was 21.9% for the heterozygote and 1.2% for the homozygote of the A allele. The obesity prevalence among the carriers of AA/AT genotypes was significantly higher than that among those with TT genotype (36.4% vs. 22.6%, P = 0.004). Compared to the carrier of TT genotype, the likelihood of obesity was 1.79 (95% confidence interval (95% CI) 1.20-2.67, P = 0.004) for the carrier of AA/AT genotype, after adjustment of sex, age and puberty stages. The BMI Z-score of children with AA/AT genotype were significantly higher than that of their counterparts with the TT genotype (1.1 ± 0.1 vs. 0.8 ± 0.1, P = 0.02). The concentration of triglyceride was 1.03 ± 0.52 mmol/L among TT carrier and 1.13 ± 0.68 mmol/L among AA/AT carrier (P = 0.045). While, the concentrations of adiponectin were 18.0 ± 0.4 μg/ml among carriers of TT and 16.2 ± 0.7 μg/ml among subjects with AA/AT genotype (P = 0.03). The level of glucose marginally increased in the AA/AT genotype subjects (4.67 ± 0.40 mmol/L vs. 4.60 ± 0.35 mmol/L, P = 0.08). The evidence of association was reduced after adjustment for BMI (P = 0.38 for triglyceride, P = 0.20 for adiponectin and glucose). There was weak evidence of association between rs9939609 and other obesity-related metabolic traits including total cholesterol (3.92 ± 0.03 mmol/L vs. 4.02 ± 0.05 mmol/L, P = 0.10), insulin (2.69 ± 1.77 ng/ml vs. 3.12 ± 2.91 ng/ml, P = 0.14), and insulin resistance (HOMA-IR 0.56 ± 0.03 vs. 0.66 ± 0.05, P = 0.10).

Conclusions
Genetic variation in the FTO gene associates with obesity in Chinese children.
Novel association of severe neonatal encephalopathy and Hirschsprung disease in a male with a duplication at the Xq28 region
Authors: Fernández Raquel M , Núñez-Torres Rocío , González-Meneses Antonio , Antiñolo Guillermo , Borrego Salud 
Published: September 2010

Abstract

Background
Hirschsprung disease (HSCR) is a neurocristopathy characterized by the absence of parasympathetic intrinsic ganglion cells in the submucosal and myenteric plexuses along a variable portion of the intestinal tract. In approximately 18% of the cases HSCR also presents with multiple congenital anomalies including recognized syndromes.

Methods
A combination of MLPA and microarray data analysis have been undertaken to refine a duplication at the Xq28 region.

Results
In this study we present a new clinical association of severe neonatal encephalopathy (Lubs syndrome) and HSCR, in a male patient carrying a duplication at the Xq28 region which encompasses the MECP2 and L1CAM genes.

Conclusions
While the encephalopathy has been traditionally attributed to the MECP2 gene duplication in patients with Lubs syndrome, here we propose that the enteric phenotype in our patient might be due to the dosage variation of the L1CAM protein, together with additional molecular events not identified yet. This would be in agreement with the hypothesis previously forwarded that mutations in L1CAM may be involved in HSCR development in association with a predisposing genetic background.
17-Allylamino-17-demethoxygeldanamycin induces downregulation of critical Hsp90 protein clients and results in cell cycle arrest and apoptosis of human urinary bladder cancer cells
Authors: Karkoulis Panagiotis K , Stravopodis Dimitrios J , Margaritis Lukas H , Voutsinas Gerassimos E 
Published: September 2010

Abstract

Background
17-Allylamino-17-demethoxygeldanamycin (17-AAG), a benzoquinone ansamycin antibiotic, specifically targets heat shock protein 90 (Hsp90) and interferes with its function as a molecular chaperone that maintains the structural and functional integrity of various protein clients involved in cellular signaling. In this study, we have investigated the effect of 17-AAG on the regulation of Hsp90-dependent signaling pathways directly implicated in cell cycle progression, survival and motility of human urinary bladder cancer cell lines.

Methods
We have used MTT-based assays, FACS analysis, Western blotting, semi-quantitative RT-PCR, immunocytochemistry and scratch-wound assay in RT4, RT112 and T24 human urinary bladder cancer cell lines.

Results
We have demonstrated that, upon 17-AAG treatment, bladder cancer cells are arrested in the G1 phase of the cell cycle and eventually undergo apoptotic cell death in a dose-dependent manner. Furthermore, 17-AAG administration was shown to induce a pronounced downregulation of multiple Hsp90 protein clients and other downstream effectors, such as IGF-IR, Akt, IKK-α, IKK-β, FOXO1, ERK1/2 and c-Met, resulting in sequestration-mediated inactivation of NF-κB, reduced cell proliferation and decline of cell motility.

Conclusions
In total, we have clearly evinced a dose-dependent and cell type-specific effect of 17-AAG on cell cycle progression, survival and motility of human bladder cancer cells, due to downregulation of multiple Hsp90 clients and subsequent disruption of signaling integrity.
Fibronectin 1 mRNA expression correlates with advanced disease in renal cancer
Authors: Waalkes Sandra , Atschekzei Faranaz , Kramer Mario W , Hennenlotter Jörg , Vetter Gesa , Becker Jan U , Stenzl Arnulf , Merseburger Axel S , Schrader Andres J , Kuczyk Markus A , Serth Jürgen 
Published: September 2010

Abstract

Background
Fibronectin 1 (FN1) is a glycoprotein involved in cellular adhesion and migration processes. The aim of this study was to elucidate the role of FN1 in development of renal cell cancer (RCC) and to determine a prognostic relevance for optimal clinical management.

Methods
212 renal tissue samples (109 RCC, 86 corresponding tissues from adjacent normal renal tissue and 17 oncocytomas) were collected from patients undergoing surgery for renal tumors and subjected to total RNA extraction. Detection of FN1 mRNA expression was performed using quantitative real time PCR, three endogenous controls, renal proximal tubular epithelial cells (RPTEC) as biological control and the ΔΔCt method for calculation of relative quantities.

Results
Mean tissue specific FN1 mRNA expression was found to be increased approximately seven fold comparing RCC and corresponding kidney control tissues (p < 0.001; ANOVA). Furthermore, tissue specific mean FN1 expression was increased approx. 11 fold in clear cell compared to papillary RCC (p = 9×10-5; Wilcoxon rank sum test). Patients with advanced disease had higher FN1 expression when compared to organ-confined disease (p < 0.001; Wilcoxon rank sum test). Applying subgroup analysis we found a significantly higher FN1 mRNA expression between organ-confined and advanced disease in the papillary and not in the clear cell RCC group (p = 0.02 vs. p = 0.2; Wilcoxon rank sum test). There was an increased expression in RCC compared to oncocytoma (p = 0.016; ANOVA).

Conclusions
To our knowledge, this is the first study to show that FN1 mRNA expression is higher in RCC compared to normal renal tissue. FN1 mRNA expression might serve as a marker for RCC aggressiveness, indicating early systemic progression particularly for patients with papillary RCC.
Educational inequalities in mortality and associated risk factors: German- versus French-speaking Switzerland
Authors: Faeh David , Bopp Matthias ,   Swiss National Cohort Study Group
Published: September 2010

Abstract

Background
Between the French- and German-speaking areas of Switzerland, there are distinct differences in mortality, similar to those between Germany and France. Assessing corresponding inequalities may elucidate variations in mortality and risk factors, thereby uncovering public health potential. Our aim was to analyze educational inequalities in all-cause and cause-specific mortality in the two Swiss regions and to compare this with inequalities in behavioural risk factors and self-rated health.

Methods
The Swiss National Cohort, a longitudinal census-based record linkage study, provided mortality and survival time data (3.5 million individuals, 40-79 years, 261,314 deaths, 1990-2000). The Swiss Health Survey 1992/93 provided cross-sectional data on risk factors. Inequalities were calculated as percentage of change in mortality rate (survival time, hazard ratio) or risk factor prevalence (odds ratio) per year of additional education using multivariable Cox and logistic regression.

Results
Significant inequalities in mortality were found for all causes of death in men and for most causes in women. Inequalities were largest in men for causes related to smoking and alcohol use and in women for circulatory diseases. Gradients in all-cause mortality were more pronounced in younger and middle-aged men, especially in German-speaking Switzerland. Mortality inequalities tended to be larger in German-speaking Switzerland whereas inequalities in associated risk factors were generally more pronounced in French-speaking Switzerland.

Conclusions
With respect to inequalities in mortality and associated risk factors, we found characteristic differences between German- and French-speaking Switzerland, some of which followed gradients described in Europe. These differences only partially reflected inequalities in associated risk factors.
Urbanization, ethnicity and cardiovascular risk in a population in transition in Nakuru, Kenya: a population-based survey
Authors: Mathenge Wanjiku , Foster Allen , Kuper Hannah 
Published: September 2010

Abstract

Background
Cardiovascular disease (CVD) is the leading cause of death among older people in Africa. This study aimed to investigate the relationship of urbanization and ethnicity with CVD risk markers in Kenya.

Methods
A cross-sectional population-based survey was carried out in Nakuru Kenya in 2007-2008. 100 clusters of 50 people aged ≥50 years were selected by probability proportionate to size sampling. Households within clusters were selected through compact segment sampling. Participants were interviewed by nurses to collect socio-demographic and lifestyle information. Nurses measured blood pressure, height, weight and waist and hip circumference. A random finger-prick blood sample was taken to measure glucose and cholesterol levels.
Hypertension was defined as systolic blood pressure (SBP) ≥140 mm Hg, or diastolic blood pressure (DBP) ≥90 mm Hg or current use of antihypertensive medication; Diabetes as reported current medication or diet control for diabetes or random blood glucose level ≥11.1 mmol/L; High cholesterol as random blood cholesterol level ≥5.2 mmol/L; and Obesity as Body Mass Index (BMI)≥30 kg/m2.

Results
5010 eligible subjects were selected, of whom 4396 (88%) were examined. There was a high prevalence of hypertension (50.1%, 47.5-52.6%), obesity (13.0%, 11.7-14.5%), diabetes (6.6%, 5.6-7.7%) and high cholesterol (21.1%, 18.6-23.9). Hypertension, diabetes and obesity were more common in urban compared to rural groups and the elevated prevalence generally persisted after adjustment for socio-demographic, lifestyle, obesity and cardiovascular risk markers. There was also a higher prevalence of hypertension, obesity, diabetes and high cholesterol among Kikuyus compared to Kalenjins, even after multivariate adjustment. CVD risk markers were clustered both across the district and within individuals. Few people received treatment for hypertension (15%), while the majority of cases with diabetes received treatment (68%).

Conclusions
CVD risk markers are common in Kenya, particularly in urban areas. Exploring differences in CVD risk markers between ethnic groups may help to elucidate the epidemiology of these conditions.
Electrocardiographic changes with the onset of diabetes and the impact of aerobic exercise training in the Zucker Diabetic Fatty (ZDF) rat
Authors: VanHoose Lisa , Sawers Youssef , Loganathan Rajprasad , Vacek James L , Stehno-Bittel Lisa , Novikova Lesya , Al-Jarrah Muhammed , Smirnova Irina V 
Published: September 2010

Abstract

Background
Early markers of diabetic autonomic neuropathy (DAN) in an electrocardiogram (ECG) include elevated R wave amplitudes, widening of QTc intervals and decreased heart rate variability (HRV). The severity of DAN has a direct relationship with mortality risk. Aerobic exercise training is a common recommendation for the delay and possible reversal of cardiac dysfunction. Limited research exists on ECG measures for the evaluation of aerobic exercise training in Zucker Diabetic Fatty (ZDF) rat, a model of type 2 diabetes. The objective of this study was to assess whether aerobic exercise training may attenuate diabetes induced ECG changes.

Methods
Male ZDF (obese fa/fa) and control Zucker (lean fa/+) rats were assigned to 4 groups: sedentary control (SC), sedentary diabetic (SD), exercised control (EC) and exercised diabetic (ED). The exercised groups began 7 weeks of treadmill training after the development of diabetes in the ED group. Baseline (prior to the training) and termination measurements included body weight, heart weight, blood glucose and glycated hemoglobin levels and ECG parameters. One way repeated measures ANOVA (group) analyzed within and between subject differences and interactions. Pearson coefficients and descriptive statistics described variable relationships and animal characteristics.

Results
Diabetes caused crucial changes in R wave amplitudes (p < 0.001), heart rate variability (p < 0.01), QT intervals (p < 0.001) and QTc intervals (p < 0.001). R wave amplitude augmentation in SD rats from baseline to termination was ameliorated by exercise, resulting in R wave amplitude changes in ED animals similar to control rats. Aerobic exercise training neither attenuated QT or QTc interval prolongation nor restored decreases in HRV in diabetic rats.

Conclusion
This study revealed alterations in R wave amplitudes, HRV, QT and QTc intervals in ZDF rats. Of these changes, aerobic exercise training was able to correct R wave amplitude changes. In addition, exercise has beneficial effect in this diabetic rat model in regards to ECG correlates of left ventricular mass.
Salirasib inhibits the growth of hepatocarcinoma cell lines in vitro and tumor growth in vivo through ras and mTOR inhibition
Authors: Charette Nicolas , De Saeger Christine , Lannoy Valérie , Horsmans Yves , Leclercq Isabelle , Stärkel Peter 
Published: September 2010

Abstract

Background
Dysregulation of epidermal growth factor and insulin-like growth factor signaling play important roles in human hepatocellular carcinoma (HCC), leading to frequent activation of their downstream targets, the ras/raf/extracellular signal-regulated kinase (ERK) and the phosphoinositide 3-kinase (PI3K)/Akt/mammalian Target of Rapamycin (mTOR) pathways. Salirasib is an S-prenyl-cysteine analog that has been shown to block ras and/or mTOR activation in several non hepatic tumor cell lines. We investigated in vitro the effect of salirasib on cell growth as well as its mechanism of action in human hepatoma cell lines (HepG2, Huh7, and Hep3B) and its in vivo effect in a subcutaneous xenograft model with HepG2 cells.

Results
Salirasib induced a time and dose dependent growth inhibition in hepatocarcinoma cells through inhibition of proliferation and partially through induction of apoptosis. A 50 percent reduction in cell growth was obtained in all three cell lines at a dose of 150 μM when they were cultured with serum. By contrast, salirasib was more potent at reducing cell growth after stimulation with EGF or IGF2 under serum-free conditions, with an IC50 ranging from 60 μM to 85 μM. The drug-induced anti-proliferative effect was associated with downregulation of cyclin A and to a lesser extent of cyclin D1, and upregulation of p21 and p27. Apoptosis induction was related to a global pro-apoptotic balance with caspase 3 activation, cytochrome c release, death receptor upregulation, and a reduced mRNA expression of the apoptosis inhibitors cFLIP and survivin. These effects were associated with ras downregulation and mTOR inhibition, without reduction of ERK and Akt activation. In vivo, salirasib reduced tumour growth from day 5 onwards. After 12 days of treatment, mean tumor weight was diminished by 56 percent in the treated animals.

Conclusions
Our results show for the first time that salirasib inhibits the growth of human hepatoma cell lines through inhibition of proliferation and induction of apoptosis, which is associated with ras and mTOR inhibition. The therapeutic potential of salirasib in human HCC was further confirmed in a subcutaneous xenograft model.
Association between CETP Taq1B and LIPC -514C/T polymorphisms with the serum lipid levels in a group of Tehran's population: a cross sectional study
Authors: Kashani Farid Mohammad Ali , Azizi Fereidoun , Hedayati Mehdi , Daneshpour Maryam S , Shamshiri Ahmad Reza , Siassi Fereydoun 
Published: September 2010

Abstract

Background
Low level of high density lipoprotein cholesterol (HDL-C) has high prevalence in the Tehran Lipid and Glucose Study (TLGS) cohort. About 50% of the inter-individual variation in serum HDL-C levels is genetically determined. Polymorphisms in cholesteryl ester transfer protein (CETP) and hepatic lipase (LIPC) genes have been found to be associated with the metabolism and serum concentration of the HDL-C.

Objectives
To determine the association between Taq1B polymorphism in CETP gene and -514C/T polymorphism in LIPC gene with serum lipid levels and lipid peroxidation in a subgroup of the TLGS population.

Results
Serum HDL-C level had significant association with CETP Taq1B polymorphism and B2B2 subjects had the highest HDL-C levels compared to B2B1 and B1B1 genotypes (37.9 vs. 36.9 and 35.3 mg/dl, respectively; P = 0.01). However, carriers of "B1" allele, in comparison to the non carriers (B2B2), had significantly lower levels of TC (200.1 vs. 215.2 mg/dl; P = 0.005), HDL-C (35.8 vs. 37.9 mg/dl; P = 0.009) and malondialdehyde MDA (4.5 vs. 5.0 nmol/mL; P=0.031). Carriers of the "T" allele in -514C/T polymorphism in LIPC gene had higher means of HDL-C than non carriers (37.7 vs. 35.7 mg/dl, P = 0.04). No other association was found between -514C/T polymorphism and any other serum lipids or MDA level.

Conclusion
This study demonstrates the association between Taq1B and -514C/T polymorphisms in the CETP and LIPC genes with the serum HDL-C levels.
Impact of pericardial adhesions on diastolic function as assessed by vortex formation time, a parameter of transmitral flow efficiency
Authors: Jiamsripong Panupong , Alharthi Mohsen S , Calleja Anna M , McMahon Eileen M , Katayama Minako , Westerdale John , Milano Michele , Heys Jeffrey J , Mookadam Farouk , Belohlavek Marek 
Published: September 2010

Abstract

Background
Pericardial adhesions are a pathophysiological marker of constrictive pericarditis (CP), which impairs cardiac filling by limiting the total cardiac volume compliance and diastolic filling function. We studied diastolic transmitral flow efficiency as a new parameter of filling function in a pericardial adhesion animal model. We hypothesized that vortex formation time (VFT), an index of optimal efficient diastolic transmitral flow, is altered by patchy pericardial-epicardial adhesions.

Methods
In 8 open-chest pigs, the heart was exposed while preserving the pericardium. We experimentally simulated early pericardial constriction and patchy adhesions by instilling instant glue into the pericardial space and using pericardial-epicardial stitches. We studied left ventricular (LV) function and characterized intraventricular blood flow with conventional and Doppler echocardiography at baseline and following the experimental intervention.

Results
Significant decreases in end-diastolic volume, ejection fraction, stroke volume, and late diastolic filling velocity reflected the effects of the pericardial adhesions. The mean VFT value decreased from 3.61 ± 0.47 to 2.26 ± 0.45 (P = 0.0002). Hemodynamic variables indicated the inhibiting effect of pericardial adhesion on both contraction (decrease in systolic blood pressure and +dP/dt decreased) and relaxation (decrease in the magnitude of -dP/dt and prolongation of Tau) function.

Conclusion
Patchy pericardial adhesions not only negatively impact LV mechanical functioning but the decrease of VFT from normal to suboptimal value suggests impairment of transmitral flow efficiency.