Association study of angiotensin-converting enzyme 2 gene (ACE2) polymorphisms and essential hypertension in northern Han Chinese.
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Angiotensin-Converting Enzyme 2↗
Biomedical subjects
Y Wang
Publications and source records attributed to Y Wang.
Association of decreased mitochondrial DNA content with ovarian cancer progression.
Mitochondrial DNA (mtDNA) content in ovarian carcinomas was assessed by quantitative PCR. Results show that mtDNA content in tumour cell was significantly higher than that in normal ovary. Change in mtDNA content was not related with patients' age or tumour stages. However, the average mtDNA copy number in pathological low-grade tumours was over two-fold higher than that in high-grade carcinomas (P=0.012). Moreover, type I carcinomas also had a significantly higher mtDNA copy number than in type II carcinomas (P=0.019). Change in mtDNA content might be an important genetic event in the progression of ovarian carcinomas.
Adenocarcinoma, Clear Cell↗
Genetic diversity of Picea asperata populations based on RAPDs.
The genetic diversity of ten natural populations of Picea asperata Mast. were studied using RAPD markers. A total of 160 reproducible fragments were produced from the ten primers used. The mean number of fragments detected per individual was 114.7. Altogether 120 fragments were polymorphic among the ten populations, none of them were found to be population-specific. Nei's expected heterozygosity (H (e)) ranged from 0.233 to 0.269, and the average was 0.247. The analysis of molecular variance revealed that the coefficient of gene differentiation among populations, based on F (ST) and the unbiased estimate PhiST, equaled 0.224 and 0.290, respectively. Such high values indicate that there is significant differentiation among populations, which could result from several factors, including restricted gene flow between populations (Nm = 0.866). Founder events may be another factor attributing to the high level of genetic differentiation. In addition, it was discovered that the geographic distribution is not correlated with the genetic distances among the populations of P. asperata.
Genetic Markers↗
Using array-comparative genomic hybridization to define molecular portraits of primary breast cancers.
We analysed 148 primary breast cancers using BAC-arrays containing 287 clones representing cancer-related gene/loci to obtain genomic molecular portraits. Gains were detected in 136 tumors (91.9%) and losses in 123 tumors (83.1%). Eight tumors (5.4%) did not have any genomic aberrations in the 281 clones analysed. Common (more than 15% of the samples) gains were observed at 8q11-qtel, 1q21-qtel, 17q11-q12 and 11q13, whereas common losses were observed at 16q12-qtel, 11ptel-p15.5, 1p36-ptel, 17p11.2-p12 and 8ptel-p22. Patients with tumors registering either less than 5% (median value) or less than 11% (third quartile) total copy number changes had a better overall survival (log-rank test: P=0.0417 and P=0.0375, respectively). Unsupervised hierarchical clustering based on copy number changes identified four clusters. Women with tumors from the cluster with amplification of three regions containing known breast oncogenes (11q13, 17q12 and 20q13) had a worse prognosis. The good prognosis group (Nottingham Prognostic Index (NPI) <or=3.4) tumors had frequent loss of 16q24-qtel. Genes significantly associated with estrogen receptor (ER), Grade and NPI were used to build k-nearest neighbor (KNN) classifiers that predicted ER, Grade and NPI status in the test set with an average misclassification rate of 24.7, 25.7 and 35.7%, respectively. These data raise the prospect of generating a molecular taxonomy of breast cancer based on copy number profiling using tumor DNA, which may be more generally applicable than expression microarray analysis.
Breast Neoplasms↗
Peripapillary atrophy in elderly Chinese in rural and urban Beijing.
PURPOSE: To determine peripapillary atrophy in elderly Chinese in an urban and rural regions of Beijing. METHODS: The Beijing Eye Study a population-based, cross-sectional cohort study, included 4,439 subjects out of 5,324 subjects who were asked to participate (response rate 83.4%). Mean age was 56.2+/-10.6 years (range, 40-101 years). Colour optic disc photographs (30 degrees ) were morphometrically examined. Peripapillary atrophy was divided into alpha zone and beta zone. RESULTS: Optic disc photographs were available for 4,027 (90.7%) subjects. Alpha zone and beta zone, respectively, were present in 2,867 (71.2%) subjects and 802 (19.9%) subjects, respectively, measuring 0.52+/-0.64 mm(2) and measuring 0.46+/-1.82 mm(2). Both zones were significantly widest and found significantly (P<0.001) most often in the temporal peripapillary region, followed by the temporal inferior region, the temporal superior region, and finally the nasal region. Size of both zones was significantly correlated with optic disc size (P<0.001), age (P<0.001), and myopic refractive error (P<0.001). Both zones increased significantly with decreasing uncorrected visual acuity (P<0.001) and decreasing best-corrected visual acuity (P<0.001). They did not vary significantly (P=0.10; and P=0.78) between male and female subjects. In multivariate analysis, the relationships between both zones and age, myopic refractive error, disc size, and uncorrected and best-corrected visual acuity remained statistically significant (P<0.001). CONCLUSIONS: Alpha zone and beta zone of peripapillary atrophy, respectively, occur in about 70 and 20%, respectively, of elderly Chinese. As peripapillary atrophy changes in glaucomatous optic neuropathy, these normative data may be helpful for glaucoma detection.
Adult↗
DYX1C1 functions in neuronal migration in developing neocortex.
Rodent homologues of two candidate dyslexia susceptibility genes, Kiaa0319 and Dcdc2, have been shown to play roles in neuronal migration in developing cerebral neocortex. This functional role is consistent with the hypothesis that dyslexia susceptibility is increased by interference with normal neural development. In this study we report that in utero RNA interference against the rat homolog of another candidate dyslexia susceptibility gene, DYX1C1, disrupts neuronal migration in developing neocortex. The disruption of migration can be rescued by concurrent overexpression of DYX1C1, indicating that the impairment is not due to off-target effects. Transfection of C- and N-terminal truncations of DYX1C1 shows that the C-terminal TPR domains determine DYX1C1 intracellular localization to cytoplasm and nucleus. RNAi rescue experiments using truncated versions of DYX1C1 further indicate that the C-terminus of DYX1C1 is necessary and sufficient to DYX1C1's function in migration. In conclusion, DYX1C1, similar to two other candidate dyslexia susceptibility genes, functions in neuronal migration in rat neocortex.
Analysis of Variance↗
High-brightness injection-seeded soft-x-ray-laser amplifier using a solid target.
We demonstrate the generation of an intense soft-x-ray-laser beam by saturated amplification of high harmonic seed pulses in a dense transient collisional soft-x-ray-laser plasma amplifier created by heating a titanium target. Amplification in the 32.6 nm line of Ne-like Ti generates laser pulses of subpicosecond duration that are measured to approach full spatial coherence. The peak spectral brightness is estimated to be approximately 2 x 10(26) photons/(s mm(2) mrad(2) 0.01% bandwidth). The scheme is scalable to produce extremely bright lasers at very short wavelengths with full temporal and spatial coherence.
Journal Article↗
Education as an important risk factor for the prevalence of hypertension and elevated blood pressure in Chinese men and women.
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Adult↗
The multikinase inhibitor midostaurin (PKC412A) lacks activity in metastatic melanoma: a phase IIA clinical and biologic study.
Midostaurin (PKC412A), N-benzoyl-staurosporine, potently inhibits protein kinase C alpha (PKCalpha), VEGFR2, KIT, PDGFR and FLT3 tyrosine kinases. In mice, midostaurin slows growth and delays lung metastasis of melanoma cell lines. We aimed to test midostaurin's safety, efficacy and biologic activity in a Phase IIA clinical trial in patients with metastatic melanoma. Seventeen patients with advanced metastatic melanoma received midostaurin 75 mg p.o. t.i.d., unless toxicity or disease progression supervened. Patient safety was assessed weekly, and tumour response was assessed clinically or by CT. Tumour biopsies and plasma samples obtained at entry and after 4 weeks were analysed for midostaurin concentration, PKC activity and multidrug resistance. No tumour responses were seen. Two (12%) patients had stable disease for 50 and 85 days, with minor response in one. The median overall survival was 43 days. Seven (41%) discontinued treatment with potential toxicity, including nausea, vomiting, diarrhoea and/or fatigue. One patient had >50% reduction in PKC activity. Tumour biopsies showed two PKC isoforms relatively insensitive to midostaurin, out of three patients tested. No modulation of multidrug resistance was demonstrated. At this dose schedule, midostaurin did not show clinical or biologic activity against metastatic melanoma. This negative trial reinforces the importance of correlating biologic and clinical responses in early clinical trials of targeted therapies.
Adult↗
Probing spin-flip scattering in ballistic nanosystems.
Because spin-flip length is longer than the electron mean-free path in a metal, past studies of spin-flip scattering are limited to the diffusive regime. We propose to use a magnetic double barrier tunnel junction to study spin-flip scattering in the nanometer sized spacer layer near the ballistic limit. We extract the voltage and temperature dependence of the spin-flip conductance Gs in the spacer layer from magnetoresistance measurements. In addition to spin scattering information including the mean-free path (70 nm) and the spin-flip length (1.0-2.6 microm) at 4.2 K, this technique also yields information on the density of states and quantum well resonance in the spacer layer.
Journal Article↗
Lack of interaction between peripheral injection of CCK and obestatin in the regulation of gastric satiety signaling in rodents.
Obestatin is a new peptide for which anorexigenic effects were recently reported in mice. We investigate whether peripheral injection of obestatin or co-injection with cholecystokinin (CCK) can modulate food intake, gastric motor function (intragastric pressure and emptying) and gastric vagal afferent activity in rodents. Obestatin (30, 100 and 300 microg/kg, i.p.) did not influence cumulative food intake for the 2h post-injection in rats or mice nor gastric emptying in rats. In rats, obestatin (300 microg/kg) did not modify CCK (1 microg/kg, i.p.)-induced significant decrease in food intake (36.6%) and gastric emptying (31.0%). Furthermore, while rats injected with CCK (0.3 microg/kg, i.v.) displayed gastric relaxation, no change in gastric intraluminal pressure was elicited by obestatin (300 microg/kg, i.v.) pre- or post-CCK administration. In in vitro rat gastric vagal afferent preparations, 20 units that had non-significant changes in basal activity after obestatin at 30 microg responded to CCK at 10 ng by a 182% increase. These data show that obestatin neither influences cumulative food intake, gastric motility or vagal afferent activity nor CCK-induced satiety signaling.
Animals↗
Performance of tPSA and f/tPSA for prostate cancer in Chinese. A systematic review and meta-analysis.
Performing a systematic review and meta-analysis to evaluate the diagnostic performance of the total prostate-specific antigen (tPSA) tests for diagnosis of prostate cancer among Chinese. Literatures related to diagnosis of prostate cancer by tPSA and the ratio of free to total PSA (f/tPSA) being retrieved in five electronic databases. Sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and diagnostic odds ratio (DOR) were pooled using random effects models. Summary receiver operating characteristic curves (SROC) used to summarize overall test performance. In total 10 studies meeting the inclusion criteria, 2256 patients were included. Among them 423 were patients of prostate cancer compared to 1833 were patients of benign prostate hyperplasia (BPH). The pooled sensitivity and specificity of tPSA>4.0 ng/ml, tPSA>10.0 ng/ml and f/tPSA<0.15 as threshold for the diagnosis of prostate cancer were heterogeneity. The areas under SROC (AUC) were 80, 85 and 87%, respectively (P<0.05). The pooled DOR were 8.44(95%CI: 4.45 approximately 16.00), 9.94(95%CI: 4.15 approximately 23.77) and 13.75(95%CI: 6.35 approximately 29.76), respectively (P<0.05). chi(2) test used for testing the heterogeneity. tPSA and f/tPSA made an important performance for diagnosis of prostate cancer in decade among Chinese. The use of f/tPSA<0.15 as threshold maintain a high prognostic accuracy for prostate cancer.
Asian People↗
Thioredoxin reduces post-ischemic myocardial apoptosis by reducing oxidative/nitrative stress.
BACKGROUND AND PURPOSE: Thioredoxin (Trx) is an oxidoreductase that prevents free radical-induced cell death in cultured cells. Here we assessed the mechanism(s) underlying the cardioprotective effects of Trx in vivo. EXPERIMENTAL APPROACH: The effects of myocardial ischemia (30 min) and reperfusion were measured in mice, with assays of myocardial apoptosis, superoxide production, NOx and nitrotyrosine content, and myocardial infarct size. Recombinant human Trx (rhTrx, 0.7-20 mg kg(-1), i.p.) was given 10 min before reperfusion. KEY RESULTS: Treatment with 2 mg kg(-1) rhTrx significantly decreased myocardial apoptosis and reduced infarct size (P<0.01). Nitrotyrosine content of cardiomyocytes was markedly reduced in rhTrx-treated animals (P<0.01). To further identify the mechanisms by which rhTrx may exert its anti-nitrative effect, iNOS expression and production of NOx and superoxide were determined. Treatment with rhTrx had no significant effect on iNOS expression or NOx content in the ischemic/reperfused heart. However, it markedly upregulated mSOD and reduced tissue superoxide content. To further establish a causative link between the anti- peroxynitrite effect and the cardioprotective effect of rhTrx, cultured adult cardiomyocytes were incubated with SIN-1, a peroxynitrite donor, (50 microM for 3 h) resulting in a nitrotyrosine content comparable to that seen in the ischemic/reperfused heart and causing significant cardiomyocyte apoptosis (P<0.01). Treatment with rhTrx markedly decreased SIN-1 induced apoptosis (P<0.01). CONCLUSIONS AND IMPLICATIONS: These results demonstrate that Trx is a novel anti-apoptotic and cardioprotective molecule that exerts its cardioprotective effects by reducing ischemia/reperfusion-induced oxidative/nitrative stress.
Animals↗
Histogranin reduced brain injury after transient focal ischemia in rats.
Excitatory amino acids (EAAs) play an important role during ischemic brain injury. In this study we examined the protective effect of histogranin (HN), an endogenous peptide that antagonizes excitatory amino acids-mediated activity noncompetitively, in an animal model of cerebral ischemia. Adult rats were anesthetized with chloral hydrate. Histogranin was given intracerebroventricularly before a 60-min middle cerebral artery occlusion (MCAo). Animals were examined for their locomotor activity 2 days after MCAo. Histogranin significantly increased locomotor activity in the stroke rats. Histogranin pretreatment reduced the volume of cerebral infarction and the caspase-3 immunoreactivity in the stroke animals. Taken together, our data suggest that histogranin is protective against ischemic brain injury. The protective effect may involve anti-apoptotic mechanisms.
Analysis of Variance↗
A protective role for programmed death 1 in progression of murine adriamycin nephropathy.
Programmed death 1 (PD-1) is a novel member of the CD28/cytotoxic T-lymphocyte-associated protein-4 superfamily, which plays an important role in the regulation of activated T cells. However, it is not clear how PD-1 is expressed in normal and diseased kidney, nor if it has a role in progression of chronic renal disease. PD-1 expression and the effect of monoclonal anti-PD-1 antibody (Ab) were examined in murine adriamycin nephropathy (AN). BALB/c mice were divided into three groups: (a) normal mice, (b) adriamycin (ADR) with control immunoglobulin (Ig)G (ADR-IgG), and (c) ADR with anti-PD-1 Ab (ADR-Ab). AN was induced by a single intravenous injection of ADR. Anti-PD-1 Ab was given by intraperitoneal injection on alternate days from day 0 to day 10, or to day 18. Animals were killed at week 4. Renal function, histological change, and cytokine expression were examined. PD-1 mRNA was detected in kidney tissue of mice with AN in a dose- and time-dependent manner. PD-1 was mainly expressed on injured tubule cells and some interstitial cells, which co-stained with alpha-smooth muscle actin in AN, but not in normal kidney. Anti-PD-1 treatment up to day 18, but not to day 10, worsened glomerular and tubulointerstitial injury. The ratio of urinary protein/creatinine was significantly higher in ADR-Ab mice than ADR-IgG mice. The number of macrophages was significantly increased in ADR-Ab mice compared with ADR-IgG mice. Blockade of PD-1 worsened progressive renal histopathological and functional injury in murine AN. This suggests a possible protective role for PD-1 in chronic renal disease, and its potential as a treatment to slow disease progression.
Actins↗
Microarray analysis of the tendinopathic rat supraspinatus tendon: glutamate signaling and its potential role in tendon degeneration.
Degenerative tendon injury or "tendinopathy" is one of the most common disorders of the musculoskeletal system. We used a rat model (Soslowsky LJ, Thomopoulos S, Tun S, Flanagan CL, Keefer CC, Mastaw J, and Carpenter JE. J Shoulder Elbow Surg 9: 79-84, 2000) to identify novel gene expression in the exercised-induced degenerated supraspinatus tendon by microarray and real-time PCR analyses. We identified several novel groups of differentially expressed genes, including those involved in apoptosis and related stress responses, and also genes that appear to be involved in glutamate signaling in tendon tissue, similar to recent findings by us in a microarray study of healing in the transected Achilles tendon of the rat (24). Until recently this kind of cellular communication was thought only to exist in cells of the central nervous system (CNS), where it is vital for CNS function. We further show that glutamate appears to induce a proapoptotic response in cultured tendon cells, similar to the "excitotoxic" response of cells in the CNS that become overstimulated. This may prove to be at least a partial cause of degeneration in overused tendon tissue and allow the development of treatments or "prehibilitation" regimens for tendinopathy based on currently used non-toxic glutamate antagonists.
Back↗
A modified electrocardiographic algorithm for differentiating typical atrioventricular node re-entrant tachycardia from atrioventricular reciprocating tachycardia mediated by concealed accessory pathway.
Non-invasive prediction of tachycardia mechanism is becoming clinically important in the era of catheter ablation for curing supraventricular tachycardia. Twelve-lead electrocardiograms (ECGs) during sinus rhythm and atrioventricular node re-entrant tachycardia (AVNRT) or atrioventricular reciprocating tachycardia (AVRT) with a narrow QRS complex were obtained from 154 consecutive adult patients who had received successful radiofrequency catheter ablation. The ECGs of initial 104 patients were analysed by three observers without knowledge of the electrophysiological diagnosis. The two arrhythmias were accurately diagnosed in 68% of cases. Three criteria were found to be discriminators of tachycardia mechanism by univariable analysis. Pseudo r/Q/S waves predicated AVNRT in 92% of cases (sensitivity 71%; specificity 95%). Retrograde P wave predicated AVRT in 86% of cases (sensitivity 75%; specificity 85%), RP interval > or =100 ms in 93% (sensitivity 71%; specificity 94%) and ST-segment elevation in lead aVR in 83% (sensitivity 71%; specficity 83%). According to the initial results, we proposed a modified stepwise ECG algorithm which used pseudo r/S/Q waves, RP interval and ST-segment elevation in lead aVR during tachycardia. Two observers assessed the modified algorithm in the remaining 50 patients. The algorithm was able to correctly diagnose the tachycardia mechanism in 84% and 87%, respectively. Using the modified algorithm can improve the accuracy and simplify the differential diagnosis between typical AVNRT and AVRT via concealed accessory pathway in adult patients.
Adult↗
Altered vitamin D metabolism in type II diabetic mouse glomeruli may provide protection from diabetic nephropathy.
The db/db mouse develops features of type II diabetes mellitus as the result of impaired signaling through its abnormal leptin receptor. In spite of accurate metabolic features of diabetes, renal disease manifestations in these mice are not as severe as in humans suggesting the presence of protective genes. There is a growing body of evidence in humans for the relevance of vitamin D in diabetes. Here we followed a large cohort of db/db mice and their non-diabetic db/+ littermates. Transcriptional profiling revealed significant upregulation of 23 genes involved in Ca2+ homeostasis and vitamin D metabolism in db/db glomeruli relative to db/+ glomeruli. Increased glomerular expression of vitamin D3 1alpha-hydroxylase, vitamin D binding protein, calbindins D9K and D28K, and calcyclin mRNA was confirmed by quantitative reverse transcription-polymerase chain reaction in 20-, 36-, and 52-week-old db/db glomeruli. Although vitamin D3 1alpha-hydroxylase protein was primarily expressed and upregulated in db/db renal tubules, it was also expressed in glomerular podocytes in vivo. Serum 1,25-dihydroxyvitamin D3 and urinary Ca2+ excretion were increased >3-fold in db/db mice compared to db/+ mice. Cultured glomerular podocytes had mRNA for vitamin D3 1alpha-hydroxylase, vitamin D receptor, and calbindin D28K, each of which was increased in high glucose conditions. High glucose also led to enhanced production of fibronectin and collagen IV protein, which was blocked by 1,25-dihydroxyvitamin D3. These results show that vitamin D metabolism is altered in db/db mice leading to metabolic and transcriptional effects. The podocyte is affected by paracrine and potentially autocrine effects of vitamin D, which may explain why db/db mice are resistant to progressive diabetic nephropathy.
25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗