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Articles by L Yang
Total Records ( 13 ) for L Yang
  T Fan , M Li , J Wang , L Yang and R. Cong

Phenoloxidase (PO) from ink sacs of Octopus ocellatus was purified by gel-filtration and ion-exchange chromatography, and characterized in terms of its biochemical and enzymatic properties by using L-dihydroxyphenylalanine (L-DOPA) as the specific substrate. It was found that prophenoloxidase from O. ocellatus was isolated as a heterodimeric protein of 153.8 kDa, and two subunits of 75.6 and 73.0 kDa were often detected in preparations after SDS activation. The PO-like activity showed optimal pH of 7.0, optimal temperature of 40°C, and an apparent Km value of 3.1 mM on L-DOPA, and 6.3 mM on catechol, respectively. The PO-like activity was extremely sensitive to 1-phenyl-2-thiourea and sodium sulfite, and very sensitive to ascorbic acid, thiourea, citric acid, and benzoic acid. Together with its specific enzyme activity on catechol and L-DOPA, it can be concluded that the Octopus PO is most probably a typical o-diphenoloxidase. The PO-like activity was also strongly inhibited by Cu2+, Zn2+, ethylenediaminetetraacetic acid and diethyldithiocarbamate (DETC), and the DETC-inhibited PO-like activity could be perfectly restored by Cu2+. These results indicated that Octopus PO is most probably a copper-containing metalloenzyme. All these results implied that the PO from O. ocellatus has the properties of a catechol-type copper-containing o-diphenoloxidase which functions not only as a catalytic enzyme in melanin production in ink sacs but also as a humoral factor in host defense via melaninization as in other crustaceans.

  D Song , X Liu , R Liu , L Yang , J Zuo and W. Liu

Connexin 43 (Cx43), known to be the main protein building blocks of gap junctions and hemichannels in mammalian heart, plays an important role in cardiocytes proliferation. Gap junctional intercellular communication has been suggested to be necessary for cellular proliferation and differentiation. However, the effect of Cx43 hemichannel on cardiocytes proliferation and the mechanism remain unclear. In this study, rat heart cell line H9c2 was used. The Cx43 location, the proliferation rate and hemichannel activity of H9c2 cells and Wnt-3a+-H9c2 cells were investigated and the changes of intracellular ATP and [Ca2+] were determined. Results showed that the inhibited hemichannel induced by 18β-glycyrrhetinic acid (GA) evoked intracellular ATP and [Ca2+] increase and enhanced H9c2 cell proliferation. Wnt-3a+-H9c2 cells displayed enhanced hemichannel activity and proliferation rate. Inhibited hemichannel of Wnt-3a+-H9c2 cells induced by 18β-GA decreased intracellular ATP, increased [Ca2+], and enhanced the proliferation of H9c2 cells. This study validated the role of hemichannel in H9c2 cell proliferation regulation, and showed a mechanism involved in the regulation of H9c2 cell proliferation. The proliferation could be enhanced by Cx43 hemichannel-mediated ATP release accompanying intracellular [Ca2+] change. However, different changes of ATP were observed in Wnt-3a+-H9c2 cells. These findings provided new insights into the molecular mechanisms of proliferation regulation in H9c2 cells and the effect of Wnt-3a on intracellular ATP.

  J. M Metzger , K Gagen , K. A Raustad , L Yang , A White , S. P Wang , S Craw , P Liu , T Lanza , L. S Lin , R. P Nargund , X. M Guan , A. M Strack and M. L. Reitman

Treatment of rodents with a bombesin receptor subtype-3 (BRS-3) agonist reduces food intake and increases fasting metabolic rate, causing weight loss with continued treatment. In small mammals, core body temperature (Tb) is regulated in part by nutritional status, with a reduced Tb during fasting. We report that fed Brs3 knockout mice have a lower Tb, which is discordant with their nutritional status. Treatment of wild-type mice with a BRS-3 agonist increased Tb, more so when the baseline Tb was reduced such as by fasting or during the inactive phase of the light cycle. With repeated BRS-3 agonist dosing, the Tb increase attenuated despite continued weight loss efficacy. The increase in Tb was not prevented by inhibitors of prostaglandin E (PGE) production but was partially reduced by a β-adrenergic blocker. These results demonstrate that BRS-3 has a role in body temperature regulation, presumably secondary to its effect on energy metabolism, including effects on sympathetic tone. By making use of this phenomenon, the reversal of the fasting Tb reduction was developed into a sensitive single-dose pharmacodynamic assay for BRS-3 agonism and other antiobesity compounds acting by various mechanisms, including sibutramine, cannabinoid-1, and melanin-concentrating hormone-1 receptor blockers, and melanocortin, β3-adrenergic, and cholecystokinin-1 receptor agonists. These drugs increased both the fasted Tb and the fasted, resting metabolic rates. The Tb assay is a robust, information-rich assay that is simpler and has a greater throughput than measuring metabolic rate and is a practical, effective tool for drug discovery.

  L Yang , J. H Kim , K. D Kovacs , J. G Arroyo and D. F. Chen

Objective  To determine whether systemic minocycline can protect photoreceptors in experimental retinal detachment (RD).

Methods  Retinal detachment was induced in mice by subretinal injection of sodium hyaluronate, 1.4%. In 1 experiment, mice received daily injections of minocycline (group 1) or saline (group 2). In a second experiment, mice were treated with minocycline or saline beginning 24 hours prior, immediately after, or 24 hours after experimental RD. In both experiments, photoreceptor cell survival and apoptosis were assessed by immunohistochemistry with primary antibodies against photoreceptor cell markers, rod rhodopsin, and cone opsin, and by terminal deoxynucleotidyl transferase-mediated dUTP-biotin end labeling.

Results  Photoreceptor cell apoptosis was detected at day 1 after experimental RD, with apoptotic cells peaking in number at day 3 and dropping by day 7. Treatment with minocycline significantly reduced the number of apoptotic photoreceptor cells associated with RD when given 24 hours before or even 24 hours after RD.

Conclusions  Our data suggest that minocycline may be useful in the treatment of photoreceptor degeneration associated with RD, even when given up to 24 hours after RD.

Clinical Relevance  Use of minocycline in patients with macula-off RD may prevent photoreceptor apoptosis and glial cell proliferation, improving final visual outcomes.

  L Yang , L Xu and L. He

Motivation: Serious adverse drug reaction (SADR) is an urgent, world-wide problem. In the absence of any well-organized gene-oriented SADR information pool, a database should be constructed. Since the importance of a gene to a particular SADR cannot simply be defined in terms of how frequently the two are cited together in the literature, an algorithm should be devised to sort genes according to their relevance to the SADR topics.

Results: The SADR-Gengle database, which is made up of gene–SADR relationships extracted from Pubmed, has been constructed, covering six major SADRs, namely cholestasis, deafness, muscle toxicity, QT prolongation, Stevens–Johnson syndrome and torsades de points. The CitationRank algorithm, which inherits the principle of the Google PageRank algorithm that a gene should be highly ranked when biologically related to other highly ranked genes, is devised. The algorithm performs robustly in recovering SADR-related genes in the presence of extraneous noise, and the use of the algorithm has been extended to sorting genes in our database. Users can browse genes in a Google-type system where genes are ordered according to their descending relevance to the SADR topic selected by the user. The database also provides users with visualized gene–gene knowledge chain networks, helping them to systematize their gene-oriented knowledge chain whilst navigating these networks.

  D. J Englot , L Yang , H Hamid , N Danielson , X Bai , A Marfeo , L Yu , A Gordon , M. J Purcaro , J. E Motelow , R Agarwal , D. J Ellens , J. D Golomb , M. C. F Shamy , H Zhang , C Carlson , W Doyle , O Devinsky , K Vives , D. D Spencer , S. S Spencer , C Schevon , H. P Zaveri and H. Blumenfeld

Impaired consciousness requires altered cortical function. This can occur either directly from disorders that impair widespread bilateral regions of the cortex or indirectly through effects on subcortical arousal systems. It has therefore long been puzzling why focal temporal lobe seizures so often impair consciousness. Early work suggested that altered consciousness may occur with bilateral or dominant temporal lobe seizure involvement. However, other bilateral temporal lobe disorders do not impair consciousness. More recent work supports a ‘network inhibition hypothesis’ in which temporal lobe seizures disrupt brainstem–diencephalic arousal systems, leading indirectly to depressed cortical function and impaired consciousness. Indeed, prior studies show subcortical involvement in temporal lobe seizures and bilateral frontoparietal slow wave activity on intracranial electroencephalography. However, the relationships between frontoparietal slow waves and impaired consciousness and between cortical slowing and fast seizure activity have not been directly investigated. We analysed intracranial electroencephalography recordings during 63 partial seizures in 26 patients with surgically confirmed mesial temporal lobe epilepsy. Behavioural responsiveness was determined based on blinded review of video during seizures and classified as impaired (complex-partial seizures) or unimpaired (simple-partial seizures). We observed significantly increased delta-range 1–2 Hz slow wave activity in the bilateral frontal and parietal neocortices during complex-partial compared with simple-partial seizures. In addition, we confirmed prior work suggesting that propagation of unilateral mesial temporal fast seizure activity to the bilateral temporal lobes was significantly greater in complex-partial than in simple-partial seizures. Interestingly, we found that the signal power of frontoparietal slow wave activity was significantly correlated with the temporal lobe fast seizure activity in each hemisphere. Finally, we observed that complex-partial seizures were somewhat more common with onset in the language-dominant temporal lobe. These findings provide direct evidence for cortical dysfunction in the form of bilateral frontoparietal slow waves associated with impaired consciousness in temporal lobe seizures. We hypothesize that bilateral temporal lobe seizures may exert a powerful inhibitory effect on subcortical arousal systems. Further investigations will be needed to fully determine the role of cortical-subcortical networks in ictal neocortical dysfunction and may reveal treatments to prevent this important negative consequence of temporal lobe epilepsy.

  B Liu , D Chen , L Yang , Y Li , X Ling , L Liu , W Ji , Y Wei , J Wang , Q Wei , L Wang and J. Lu

Mitogen-activated protein kinase kinase 4 (MKK4) is a critical mediator of stress-activated protein kinase signals that regulate apoptosis, inflammations and tumorigenesis. Several polymorphisms have been identified in the MKK4 gene. We hypothesized that genetic variants in the MKK4 promoter may alter its expression and thus cancer risk. In a case–control study of 1056 lung cancer cases and 1056 sex and age frequency-matched cancer-free controls, we genotyped two common polymorphisms in the MKK4 promoter region (–1304T>G and –1044A>T) with the Taqman assay, and we found that compared with the most common –1304TT genotype, carriers of –1304G variant genotypes had a decreased risk of lung cancer [odds ratio (OR) = 0.74; 95% confidence interval (CI) = 0.61–0.90 for TG, and OR = 0.62; 95% CI = 0.41–0.94 for GG] in an allele dose–response manner (adjusted Ptrend = 0.0005). Further stratification analysis showed that the protective role of the –1304G variant allele was more evident in low or normal body mass index (BMI) but restrained in the overweighters and that the –1304G variant genotypes interacted with BMI in reducing cancer risk (adjusted Pinteraction = 0.003). Moreover, the luciferase assay showed that the G allele in the promoter significantly increased the transcription activity of the MKK4 gene in vitro and that the MKK4 protein expression levels of the G variant carriers was significantly higher in tumor tissues than those of the –1304TT genotype. However, no significant association was observed between the –1044A>T polymorphism and risk of lung cancer. Our data suggest that the functional –1304G variant in the MKK4 promoter contributes to a decreased risk of lung cancer by increasing the promoter activity and that the G variant may be a marker for susceptibility to lung cancer.

  K Rodriguez Capote , C. M Balion , S. A Hill , R Cleve , L Yang and A. El Sharif

Background: Urine myoglobin continues to be used as a marker of rhabdomyolysis, particularly to assess risk of developing acute renal failure and evaluate treatment success. We sought to determine the predictive validity of urine myoglobin (uMb) for acute renal failure (ARF) in patients with suspected rhabdomyolysis.

Methods: We performed a broad systemic review of the literature from January 1980 to December 2006 using the search terms myoglobin$ AND (renal OR ARF OR kidney). Only primary studies published in English where uMb measurement was related to ARF were included.

Results: Of 1602 studies screened, 52 met all selection criteria. The studies covered a wide spectrum of etiologies for rhabdomyolysis, dissimilar diagnostic criteria for ARF and rhabdomyolysis, and various methods of uMb measurement and were mostly case series (n = 32). There was poor reporting on the uMb method, and 17 studies failed to provide any information about the method. The reporting of clinical criteria for ARF with respect to timing, description, performance, and interpretation also lacked adequate detail for replication. Eight studies (total 295 patients) had data for 2-by-2 tables. Sensitivity of the uMb test was 100% in 5 of the 8 studies, specificity varied widely (15% to 88%), and CIs around these measures were high. Pooling of data was not possible because of study heterogeneity.

Conclusions: There is inadequate evidence evaluating the use of uMb as a predictor of ARF in patients with suspected rhabdomyolysis.

  Y Wu , L Yang , T Su , C Wang , G Liu and X. m. Li

Background and objectives: Although a renal biopsy is indispensable for depicting the severity of pathologic lesions in drug-induced tubulointerstitial nephritis (DTIN), it is not acceptable in some cases and cannot be performed serially because of its invasive nature. Therefore, the discovery of noninvasive markers that are closely related to the pathology of DTIN is of great value.

Design, setting, participants, & measurements: In this study, the urinary levels of monocyte chemotactic peptide-1 (MCP-1), neutrophil gelatinase-associated lipocalin (NGAL), N-acetyl-β-d-glucosaminidase, and 1-microglobulin were measured in 40 DTIN subjects, and the performances of these parameters for distinguishing different pathologic lesions were compared.

Results: Linear correlation and receiver operating characteristic curve analyses showed that urinary MCP-1 levels were able to identify serious interstitial edema and inflammatory infiltration with greater accuracy than the other biomarkers (r = 0.501, P < 0.001 and r = 0.768, P < 0.001, respectively), whereas urinary NGAL levels showed the highest correlation coefficient with tubular atrophy (r = 0.692, P < 0.001).

Conclusions: These results suggest that these biomarker levels were higher in patients with DTIN than in controls. Urinary MCP-1 levels correlated and were predictive of the gradated severity of acute lesions in DTIN, whereas the roles of NGAL and 1-microglobulin in chronic alterations require further study.

  J Gu , W Yang , J Cheng , T Yang , Y Qu , Y Kuang , H Huang , L Yang , W He and L. Min

To analyse the temporal and spatial characteristics of traumatic brain injury and the distribution of combined injuries in the Wenchuan earthquake, and describe the treatment opportunities and preferences for therapy.


The diagnosis and treatment of 92 patients with traumatic brain injury who survived the massive earthquake (magnitude 8) in Wenchuan, Sichuan Province, on 12 May 2008 were systematically analysed.


The patients all came from the plains northwest of Chengdu city. Seventy-six patients were admitted during the early stage (within 12 h) after the earthquake. Ten patients underwent surgery and three patients died.


Patients with traumatic brain injury during the early period accounted for a large proportion of the patients wounded in the Wenchuan earthquake, and their conditions changed quickly. The patients all came from the plain area which has convenient transportation. After admission, providing first-aid early had a significant effect on increasing the success of treatment for these patients.

  W. H Zhu , L Yang , C. Q Jiang , L. Z Deng , T. H Lam , J. Y Zhang and S. S. C. Chan

Smoking cessation programs are well established in the West, but reports on smoking cessation clinics (SCCs) from China are lacking. On the basis of the Hong Kong experience and with strong support from Guangzhou Health Bureau, we established the first SCC in Guangzhou, China. The objective was to describe the characteristics of smokers, measure quit rates and examine predictors of successful quitting.


During 2006–08, 220 smokers received individual counseling following the five A's and five R's. No medications were used.


At baseline, the mean (SD) age was 40 (14) years. Most (96%) were males, married (73%), currently employed (75%), college educated or above (54%); 77% had previous quitting attempts. By 14 May 2008, 195 reached the 6 months follow-up period. Of them, 79% (151/195) were successfully followed up, and 46 had quit. By intention to treat, the 6-month 7-day point prevalence quit rate was 24% [95% confidence interval (CI) 18–30%]. Smokers with more confidence in quitting or were at action stage were more successful in quitting with adjusted odds ratio of 2.39 (95% CI 1.01–5.30) and 5.50 (95% CI 1.08–28) respectively.


A pilot-model clinic free of charge and with systemic data collection, follow-up and evaluation should be a starting point for smoking cessation program in low-income countries.

  S Li , D Zhang , L Yang , J. V Burnier , N Wang , R Lin , E. R Lee , R. I Glazer and P. Brodt

The IGF-I receptor (IGF-IR) was identified as a tumor progression factor, but its role in invasion and metastasis has been the subject of some controversy. Previously we reported that in murine lung carcinoma M-27 cells, overexpression of IGF-IR increased the synthesis and activation of matrix metalloproteinase (MMP)-2 via Akt/phosphatidylinositol 3-kinase signaling. In contrast, we show here that in these and other cells, IGF-IR overexpression reduced the constitutive and phorbol 12-myristate 13-acetate (PMA)-inducible expression of three protein kinase C (PKC)-regulated metalloproteinases, MMP-3, MMP-9, and MMP-13, in cultured cells as well as in vivo in sc tumors. To elucidate the underlying mechanism, we analyzed the effect of IGF-IR on PKC expression and activity using wild-type and IGF-IR-overexpressing (M-27IGFIR) tumor cells. Our results show that overexpression and activation of IGF-IR reduced PKC- expression, PKC activity, and downstream ERK1/2 signaling, and these effects were reversed in cells expressing kinase (Y1131,1135,1136F) or C-terminal (Y1250/51F) domain mutants of IGF-IR. This reduction was due to transcriptional down-regulation of PKC- as evidenced by reduced PKC- mRNA expression in a phosphatidylinositol 3-kinase-dependent manner and a blockade of PKC- promoter activation as revealed by a reporter gene assay. Finally, reconstitution of PKC- levels could restore MMP-9 expression levels in these cells. Collectively, these results show that IGF-IR can inhibit PKC- gene transcription and thereby block the synthesis of PMA-regulated MMPs, suggesting that within the same cells, IGF-IR can act as both a positive and negative regulator of MMP expression and function.

  M. Q Xu , W. S Sun , B. X Liu , G. Y Feng , L Yu , L Yang , G He , P Sham , E Susser , D St. Clair and L. He

Objective: Evidence from the 1944–1995 Dutch Hunger Winter and the 1959–1961 Chinese famines suggests that those conceived or in early gestation during famines, have a 2-fold increased risk of developing schizophrenia in adult life. We tested the hypothesis in a second Chinese population and also determined whether risk differed between urban and rural areas. Method: The risk of schizophrenia was examined in Liuzhou prefecture of Guangxi autonomous region. Rates were compared among those conceived before, during, and after the famine years. Based on the decline in birth rates, we predicted that those born in 1960 and 1961 would have been exposed to the famine during conception or early gestation. All psychiatric case records in Liuzhou psychiatric hospital for the years 1971 through 2001 were examined and clinical/sociodemographic data extracted by psychiatrists blind to exposure status. Data on births and deaths in the famine years were also available, and cumulative mortality was estimated from later demographic surveys. Evidence of famine was verified, and results were adjusted for mortality. Relative risks (RRs) for schizophrenia were calculated for the region as a whole and for urban and rural areas separately. Results: Mortality-adjusted RR for schizophrenia was 1.5 (1960) and 2.05 (1961), respectively. However, the effect was exclusively from the rural areas RR = 1.68 (1960) and RR = 2.25 (1961). Conclusions: We observe a 2-fold increased risk of schizophrenia among those conceived or in early gestation at the height of famine with risk related to severity of famine conditions.

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