Associations of IL-1ß and IL-6 gene polymorphisms with Parkinson's disease.

OBJECTIVE: The aim of this study was to explore the associations of interleukin-1ß (IL-1ß) and IL-6 gene polymorphisms with the pathogenesis of Parkinson's disease. PATIENTS AND METHODS: A total of 200 patients with Parkinson's disease in our hospital were collected as the disease group. Meanwhile, 200 healthy subjects were taken as the control group. Peripheral blood samples were drawn from all research subjects. The polymorphic regions of IL-1ß and IL-6 were amplified via polymerase chain reaction (PCR). Moreover, the polymorphisms were detected and analyzed, followed by further analysis based on the changes in gene expressions and Hoehn-Yahr grade of patients. RESULTS: The allele distributions at IL-1ß rs571556428 (p=0.015) and IL-6 rs543214973 (p=0.012) were statistically different between control group and disease group. In disease group, the G allele frequency at IL-1ß rs571556428 and T allele frequency at IL-6 rs543214973 were significantly higher (p<0.05). Genotype distributions at IL-1ß rs572292175 (p=0.017) and rs571556428 (p=0.000), and IL-6 rs543214973 (p=0.002) in disease group were also different from those in control group. In addition, the frequencies of CT genotype at IL-1ß rs572292175, AA genotype at IL-1ß rs571556428 and AA genotype at IL-6 rs543214973 in disease group were significantly lower (p<0.05). After modeling and analysis, it was found that the distribution of recessive model at IL-1ß rs571556428 (p=0.012) and IL-6 rs543214973 (p=0.014) in disease group exhibited significant differences from those in control group. The frequencies of TA haplotype at IL-1ß rs572292175 and rs571556428 (p=0.038) and GA haplotype at IL-6 rs1474348 and rs543214973 (p=0.047) in disease group were lower than those in control group (p<0.05). The polymorphisms at IL-1ß rs571556428 and IL-6 rs1474348 were significantly associated with gene expression (p<0.05). Moreover, the expressions of IL-1ß and IL-6 rose significantly in patients with GG genotype at rs571556428 and CG genotype at rs1474348, respectively (p<0.05). Furthermore, the polymorphism at IL-1ß rs571556428 was significantly correlated with the grade of Parkinson's disease (p=0.000). Parkinson's disease was in a higher grade (grade 4-5) in patients with AA genotype, whereas in a lower grade (grade 1-2) in patients with GG and AG genotypes. CONCLUSIONS: IL-1ß and IL-6 gene polymorphisms are significantly associated with the pathogenesis of Parkinson's disease.

Long-Term Outcome of Liver Transplant Recipients After the Development of Renal Failure Requiring Dialysis: A Study Using the National Health Insurance Database in Taiwan.

BACKGROUND: The aims of this study were to identify the incidence of renal failure requiring dialysis and to investigate the long-term outcome after renal failure in liver transplantation (LT) patients. METHODS: The primary database used was the Taiwan National Health Insurance Research Database. Subjects with LT from 1997 to 2009 were included. Patients were grouped into the dialysis cohort if they once received hemodialysis owing to any pattern of renal failure during peri-transplantation periods or after LT. Otherwise, they were categorized into the nondialysis cohort. We conducted a retrospective observational study on the correlation of renal failure requiring dialysis and its effect on LT recipients. RESULTS: The analysis included data of 1,771 LT recipients with a mean follow-up time of 3.8 ± 2.9 years. The mean age was 43.2 ± 19.3 years, and 69.4% were male. Overall patient survival was 86.2% at 1 year, 82.2% at 3 years, and 80.5% at 5 years. Renal failure requiring dialysis had developed in the 323 patients (18.2%). Among them, 26 individuals (1.5%) had progressed to end-stage renal disease without renal recovery after perioperative hemodialysis. Individuals who developed renal failure requiring dialysis had a higher mortality compared with LT recipients never requiring dialysis (hazard ratio, 8.75; 95% confidence interval, 7.0-10.9). CONCLUSIONS: Renal failure requiring dialysis development after LT is common and carries high mortality in Chinese liver allograft recipients. Recognizing risk factors permits the timely institution of proper treatment, which is the key to reducing untoward outcomes.

SOX4 is a potential prognostic factor in human cancers: a systematic review and meta-analysis

Objective. The aim of the this study was to analyze the status of sex-determining region Y-related high-mobility group box 4 (SOX4) expression in varied human cancers and its correlation with overall survival in patients with human cancers. Methods. To observe initially the expression status of SOX4 in twenty kinds of human cancers at protein database (The Human Protein Atlas). We systematically and carefully searched the studies from electronic databases and seriously identified according to eligibility criteria. The correlation between SOX4 expression and overall survival in human cancers was evaluated through Review Manager. Results. We found that SOX4 expression was significantly positive in most types of human cancer tissues, and the positive rate of SOX4 expression was about 78 % in overall cancer tissues. Furthermore, a total of 10 studies which included 1348 cancer patients were included in the final analysis. Meta-analysis showed that SOX4 overexpression was correlated with a poor overall survival and the pooled hazard ratio (HR), and corresponding 95 % confidence interval (CI) was 1.67 (95 % CI 1.01-2.78). From subgroup analyses, we present evidence that SOX4 overexpression was an unfavorable prognostic factor for colorectal cancer patients’ recurrence-free survival and gastric cancer patients’ overall survival, and the pooled HRs (95 % CI) were 1.73 (95 % CI 1.04-2.88) and 3.74 (95 % CI 1.04-13.45), respectively. Conclusions. In summary, SOX4 is a potential prognostic biomarker in human cancers (AU)

No disponible

The role of TNF-α, IL-6, IL-10, and GDNF in neuronal apoptosis in neonatal rat with hypoxic-ischemic encephalopathy.

AIM: To examine the dynamic changes of TNF-α, IL-6, IL-10, and GDNF (glial cell-derived neurotrophic factor) in serum or brain tissues of neonatal rat with hypoxic-ischemic encephalopathy and to explore their roles in neuronal apoptosis. MATERIALS AND METHODS: A total of 80 Wistar rats were randomly divided into the sham-operated (control) group and the hypoxia-ischemia (HI) group. To establish the hypoxic-ischemic encephalopathy (HIE) model, the pups from the HI group were subjected to left common carotid artery ligation followed by exposure to 8% O2 and 92% N2. The concentration of TNF-α, IL-6, IL-10, and GDNF in serum or brain tissues was measured by enzyme linked immunosorbent assay (ELISA). Neuronal apoptosis was examined by flow cytometry (FC). Statistical analysis was performed using the SPSS13.0 software. RESULTS: We found that the neuronal apoptosis rate and the levels of TNF-α and IL-6 in rat with hypoxic-ischemic brain damage (HIBD) were significantly increased at 6 h, 24 h, 48 h, and 72 h after hypoxia compared to the control group (p < 0.05). We also found that the neuronal apoptosis rate was positively correlated with the levels of TNF-α and IL-6, and negatively correlated with IL-10 and GDNF. CONCLUSIONS: In neonatal rats with HIE, the brain reaches its peak levels of damage by 24~72 h after the injury. Inflammatory cytokines such as TNF-α and IL-6 promote HIE-induced neuronal apoptosis, whereas IL-10 and GDNF antagonize it.

Statin administration does not improve the mobilization of very small embryonic-like stem cells (VSELs) in contrast to resveratrol treatment in a murine model of acute myocardial infarction.

We have found that short-term statin treatment plus stem cell transplantation in acutely infarcted hearts improves cardiac function because statins promote the efficacy of cellular cardiomyoplasty. Autologous Sca-1(+)Lin(-)CD45(-)(CXCR(+)) very small embryonic-like stem cell (VSEL) mobilization in acute myocardial infarction (AMI) correlates with the preservation of cardiac function. Whether short-term atorvastatin (Ator) can enhance the mobilization or recruitment of VSELs in AMI is still unclear. We divided mice into 4 groups: 1) sham; 2) AMI; 3) AMI+resveratrol (RSV) as a positive control; and 4) AMI+Ator. There was an increase in the circulating VSEL/full population of leukocytes (FPL) ratio 48 hours after AMI, and AMI+RSV increased it further. Ator administration did not increase the VSEL/FPL ratio. The cardiac stromal cell-derived factor-1 (SDF-1) and SDF-1alpha levels were in agreement with the results of VSEL mobilization. One week after AMI, more Sca-1(+)CXCR(+) cells were recruited to the myocardium of AMI+RSV mice but not AMI+Ator mice. Short-term Ator administration failed to upregulate cardiac SDF-1 and could not enhance the recruitment of VSELs early after AMI.

Remote THz generation from two-color filamentation: long distance dependence.

Remote terahertz (THz) generation from two-color filamentation is investigated as a function of the onset position of filaments. THz signals emitted by filaments produced at distances up to 55 m from the laser source were measured. However, from 9 m to 55 m, the THz signal decayed monotonically for increasing onset positions. With a simple calculation, the dominant factors associated to this decay were identified as group velocity mismatch of the two-color pulses and linear diffraction induced by focusing and propagating the second harmonic pulse.

Kinetic migration of isothiazolinone biocides from paper packaging to Tenax and Porapak.

Migration investigations were carried out on paper packaging materials in contact with solid food simulants. The aim was to investigate the migration behaviour of a series of isothiazolinone biocides (2-methyl-3-isothiazolinone (MI), 1,2-benzisothiazolinone (BIT) and 2-octyl-3-isothiazolinone (OIT)) as potential contaminants in paper materials, at varying temperatures and migration times, for the food simulants Tenax and Porapak. Based on the migration results, Tenax was found to be a good food simulant, and was more suitable than Porapak at high temperature. Petri dishes were found to be suitable for use as migration cells when the compounds to be evaluated were non-volatile. The amount of migration gradually increased with time and increasing temperature, finally reaching a steady value. When the temperature was higher than the boiling point of OIT, the migration rate decreased because of volatilization. The maximum migration rates were 3.4% for MI, 2.2% for BIT and 10.6% for OIT at high temperature (≥100 °C). Two kinds of paper packaging for food were tested with the method that was developed. OIT in the papers migrated into the food simulants but the amount that migrated was less than 0.14 µg kg(-1).

Analysis of isothiazolinone biocides in paper for food packaging by ultra-high-performance liquid chromatography-tandem mass spectrometry.

A novel and simple method to detect isothiazolinone-type biocides (2-methyl-3-isothiazolinone (MI), 5-chloro-2-methyl-3-isothiazolinone (CMI), 1,2-benzisothiazolinone (BIT) and 2-octyl-3-isothiazolinone (OIT)) in paper used for food packaging by ultrasonic extraction coupled with UPLC-MS/MS was developed. Parameters affecting process efficiency such as extraction solvents, UPLC mobile phase, gradient elution procedure and MS/MS conditions were studied to optimise the operating conditions. Using the optimised gradient elution procedure, the retention time was less than 6 min. The limits of detection (LODs) were found to be between 0.001 and 0.010 mg kg⁻¹, which was validated using actual concentrations. After diluting the standard solution with a blank matrix, the linear calibration curve ranges were 0.002-1.000 mg kg⁻¹ for BIT and OIT, 0.005-1.000 mg kg⁻¹ for MI, and 0.020-1.000 mg kg⁻¹ for CMI, with correlation coefficients higher than 0.9985 (n = 6). A good level of precision with a mean recovery greater than 81.3% and a relative standard deviation (RSD) less than 6.2% were also obtained. A methodology has been proposed for the analysis of isothiazolinones in paper.

The immediate large-scale dendritic plasticity of cortical pyramidal neurons subjected to acute epidural compression.

Head trauma and acute disorders often instantly compress the cerebral cortex and lead to functional abnormalities. Here we used rat epidural bead implantation model and investigated the immediate changes following acute compression. The dendritic arbors of affected cortical pyramidal neurons were filled with intracellular dye and reconstructed 3-dimensionally for analysis. Compression was found to shorten the apical, but not basal, dendrites of underlying layer III and V cortical pyramidal neurons and reduced dendritic spines on the entire dendritic arbor immediately. Dendrogram analysis showed that in addition to distal, proximal apical dendrites also quickly reconfigured. We then focused on apical dendritic trunks and explored how proximal dendrites were rapidly altered. Compression instantly twisted the microtubules and deformed the membrane contour of dendritic trunks likely a result of the elastic nature of dendrites as immediate decompression restored it and stabilization of microtubules failed to block it. Subsequent adaptive remodeling restored plasmalemma and microtubules to normal appearance in 3 days likely via active mechanisms as taxol blocked the restoration of microtubules and in addition partly affected plasmalemmal reorganization which presumably engaged recycling of excess membrane. In short, the structural dynamics and the associated mechanisms that we revealed demonstrate how compression quickly altered the morphology of cortical output neurons and hence cortical functions consequently.

Characterization of HLA-G expression in renal cell carcinoma.

Previous studies showed that human leukocyte antigen (HLA)-G is specifically upregulated in renal cell carcinoma (RCC). However, a larger cohort of RCC patients are necessary to obtain more information. In this study, 109 RCC primary lesions (clear cell, n = 95; chromophobe, n = 4; papillary, n = 4; collecting duct, n = 6) and corresponding adjacent tumor-negative renal tissues (n = 34) were analyzed for the HLA-G expression by immunohistochemistry (IHC). Meanwhile, plasma soluble HLA-G (sHLA-G) from 16 RCC patients and 144 sex- and age-matched normal individuals was detected by enzyme-linked immunosorbent assay. Correlations between lesion HLA-G expression and various clinical parameters were evaluated. Receiver-operating characteristic (ROC) curve analysis was used to determine the feasibility of HLA-G protein staining and sHLA-G as a diagnosis marker for RCC. IHC data showed that HLA-G was observed in 49.5% of clear cell, 50% of either chromophobe or collecting duct RCC lesions but undetectable in papillary RCC and tumor-negative renal tissues. This finding was consistent with the western blot results. sHLA-G was pronouncedly increased in RCC patients when compared with normal controls (median: 39.5 vs 19.2 U/ml, P = 0.002). However, no correlation was observed between HLA-G expression and various clinical parameters. We found that the area under ROC curve for HLA-G expression and sHLA-G was 0.739 [95% confidence interval (95% CI): 0.659-0.816, P = 0.000] and 0.733 (95% CI: 0.619-0.847, P = 0.002), respectively. Our findings indicated that, except the papillary RCC, other types of RCC could express HLA-G. Furthermore, both lesion HLA-G expression and plasma sHLA-G level might be a useful preoperative biomarker for diagnosis.

Fatigue reversibly reduced cortical and hippocampal dendritic spines concurrent with compromise of motor endurance and spatial memory.

Fatigue could be induced following forced exercise, sickness, heat stroke or sleep disturbance and impaired brain-related functions such as concentration, attention and memory. Here we investigated whether fatigue altered the dendrites of central neurons. Central fatigue was induced by housing rats in cage with 1.5-cm deep water for 1-5 days. Three days of sleep deprivation seriously compromised rats' performance in weight-loaded forced swimming and spatial learning tests, and 5 days of treatment worsened it further. Combinations of intracellular dye injection and three-dimensional analysis revealed that dendritic spines on retrograde tracer-identified corticospinal neurons and Cornu Ammonis (CA)1 and CA3 pyramidal neurons were significantly reduced while the shape or length of the dendritic arbors was not altered. Three days of rest restored the spine loss and the degraded spatial learning and weight-loaded forced swimming performances to control levels. In conclusion, although we could not rule out additional non-hypothalamic-pituitary-adrenal stress, the apparent fatigue induced following a few days of sleep deprivation could change brain structurally and functionally and the effects were reversible with a few days of rest.

The cytoarchitecture and soma-dendritic arbors of the pyramidal neurons of aged rat sensorimotor cortex: an intracellular dye injection study.

We studied the cytoarchitecture and dendritic arbors of the output neurons of the sensorimotor cortex of aged rats and found that although individual cortical layer became thinner, the overall cytoarchitecture and neuron densities remained comparable to those of young adults. To find out whether aging affects cortical outputs we studied the soma-dendritic arbors of layers III and V pyramidal neurons, main output neurons of the cerebral cortex, using brain slice intracellular dye injection technique. With a fluorescence microscope, selected neurons were filled with fluorescence dye under visual guidance. Injected slices were resectioned into thinner sections for converting the injected dye into non-fading material immunohistochemically. The long apical dendritic trunk and branches could be routinely revealed. This allowed us to reconstruct and study the dendritic arbors of these neurons in isolation in 300-microm-thick dimension. Analysis shows that their cell bodies did not shrink, but the densities of spines on dendrites and the total dendritic length significantly reduced. Among spines, those with long thin stalks thought to be involved in memory acquisition appeared to be reduced. These could underlie the compromise of sensorimotor functions following aging.

Changes of the ocular refraction among freshmen in National Taiwan University between 1988 and 2005.

PURPOSE: The prevalence of myopia in Taiwan has been reported to be increasing in the sequential nationwide survey. The purpose of this study is to compare the change of ocular refraction among freshmen in 1988 and 2005 in National Taiwan University. METHODS: The refractive status of freshmen in National Taiwan University in 2005 was examined. The refractive status and corneal radius of each student were measured with autorefractometer. The data was compared with the data obtained in 1988. All the refractions of the right eye were chosen and myopia was defined as a mean spherical equivalent of -0.25 D or more. RESULTS: The mean refractive status of total 4686 freshmen was -4.25+/-2.74 D in 1988 (-4.12+/-2.72 D for males and -4.41+/-2.75 D for females). The prevalence of myopia was 91.3% (90.1% for males and 92.8% for females). The prevalence of high myopia (over -6.0 D) was 23.5% (22.2% for males and 25.1% for females). In 2005, the mean refractive status of total 3709 freshmen was -4.93+/-2.82 D (-4.93+/-2.83 D for males and -4.93+/-2.80 D for females). The prevalence of myopia was 95.9% (95.9% for males and 95.9% for females). The prevalence of high myopia was 38.4% (38.1% for males and 38.8% for females). CONCLUSIONS: The prevalence and severity of myopia in freshmen of National Taiwan University increased significantly in 2005 compared to 1988. The distribution of refractive status in different college changed also. These findings may be explained by the early onset of myopia.

Valgancyclovir as maintenance therapy for cytomegalovirus retinitis in a lung transplant patient--a case report.

UNLABELLED: The purpose of this article is to report the use of valgancyclovir as maintenance therapy for cytomegalovirus (CMV) retinitis in a lung transplanted patient. RESULT: A 30-year-old woman with underlying pulmonary lymphangioleiomyomatosis received a lung transplant 1 year ago. CMV retinitis developed 4 months later but subsided after intravenous ganciclovir treatment. Unfortunately, the CMV retinitis recurred three times in 1 year while on oral ganciclovir maintenance therapy. To treat the latest relapse, valgancyclovir 900 mg once daily was used as maintenance therapy after intravenous gancyclovir induction. With a 6-month follow-up, the fundoscopic examination revealed old atrophic scar and no active CMV retinits. The patient was able to maintain best-corrected visual acuity of 20/20 in both eyes. In conclusion, Valganciclovir may be used as maintenance therapy in CMV retinitis.

Mutation in the FGFR2 gene in a Taiwanese patient with Beare-Stevenson cutis gyrata syndrome.

The present authors report the first case of Beare-Stevenson syndrome in Taiwan. The patient shares several clinical characteristics of Beare-Stevenson syndrome such as cutis gyrata, cloverleaf skull, prominent eyes, cleft palate, ear defects and a protruding umbilical stump. Molecular genetic analysis of the FGFR2 gene in this patient's DNA revealed a missense A --> G mutation on nucleotide 1303 of the FGFR2 cDNA. This mutation leads to a Tyr --> Cys substitution at residue 375 located at the N-terminal end of the transmembrane domain of FGFR2. The present results are in accordance with other previously published reports and strengthen the importance of the FGFR2 gene in the pathogenesis of Beare-Stevenson syndrome.

Measurement of the total cross section for hadronic production by e(+)e(-) annihilation at energies between 2.6-5 GeV

Using the upgraded Beijing Spectrometer, we have measured the total cross section for e(+)e(-) annihilation into hadronic final states at center-of-mass energies of 2.6, 3.2, 3.4, 3.55, 4.6, and 5.0 GeV. Values of R, sigma(e(+)e(-)-->hadrons)/sigma(e(+)e(-)-->&mgr;(+)&mgr;(-)), are determined.