The Chinese University of Hong Kong

About: The Chinese University of Hong Kong is a education organization based out in Hong Kong, China. It is known for research contribution in the topics: Population & Cancer. The organization has 43411 authors who have published 93672 publications receiving 3066651 citations.

Agency Problems at Dual-Class Companies

Abstract: We use a sample of U.S. dual-class companies to examine how the divergence between insider voting rights and cash-flow rights affects managerial extraction of private benefits of control. We find that as the divergence widens at dual-class companies, corporate cash holdings are worth less to outside shareholders, CEOs receive higher levels of compensation, managers are more likely to make shareholder-value destroying acquisitions, and capital expenditures contribute less to shareholder value. These findings support the hypothesis that managers with greater control rights in excess of cash-flow rights are prone to waste corporate resources to pursue private benefits at the expense of shareholders. As such, they contribute to our understanding of why firm value is decreasing in the insider control-cash flow rights divergence.

Development of Lifetime Comorbidity in the World Health Organization World Mental Health Surveys

Abstract: Context Although numerous studies have examined the role of latent variables in the structure of comorbidity among mental disorders, none has examined their role in the development of comorbidity. Objective To study the role of latent variables in the development of comorbidity among 18 lifetime DSM-IV disorders in the World Health Organization World Mental Health Surveys. Design Nationally or regionally representative community surveys. Setting Fourteen countries. Participants A total of 21 229 survey respondents. Main Outcome Measures First onset of 18 lifetime DSM-IV anxiety, mood, behavior, and substance disorders assessed retrospectively in the World Health Organization Composite International Diagnostic Interview. Results Separate internalizing (anxiety and mood disorders) and externalizing (behavior and substance disorders) factors were found in exploratory factor analysis of lifetime disorders. Consistently significant positive time-lagged associations were found in survival analyses for virtually all temporally primary lifetime disorders predicting subsequent onset of other disorders. Within-domain (ie, internalizing or externalizing) associations were generally stronger than between-domain associations. Most time-lagged associations were explained by a model that assumed the existence of mediating latent internalizing and externalizing variables. Specific phobia and obsessive-compulsive disorder (internalizing) and hyperactivity and oppositional defiant disorders (externalizing) were the most important predictors. A small number of residual associations remained significant after controlling the latent variables. Conclusions The good fit of the latent variable model suggests that common causal pathways account for most of the comorbidity among the disorders considered herein. These common pathways should be the focus of future research on the development of comorbidity, although several important pairwise associations that cannot be accounted for by latent variables also exist that warrant further focused study.

Pathology of fatal human infection associated with avian influenza A H5N1 virus.

Abstract: Eighteen cases of human influenza A H5N1 infection were identified in Hong Kong from May to December 1997. Two of the six fatal cases had undergone a full post-mortem which showed reactive hemophagocytic syndrome as the most prominent feature. Other findings included organizing diffuse alveolar damage with interstitial fibrosis, extensive hepatic central lobular necrosis, acute renal tubular necrosis and lymphoid depletion. Elevation of soluble interleukin-2 receptor, interleukin-6 and interferon-gamma was demonstrated in both patients, whereas secondary bacterial pneumonia was not observed. Virus detection using isolation, reverse transcription-polymerase chain reaction and immunostaining were all negative. It is postulated that in fatal human infections with this avian subtype, initial virus replication in the respiratory tract triggers hypercytokinemia complicated by the reactive hemophagocytic syndrome. These findings suggest that the pathogenesis of influenza A H5N1 infection might be different from that of the usual human subtypes H1-H3.

Oncofetal H19-derived miR-675 regulates tumor suppressor RB in human colorectal cancer.

Abstract: H19 is an imprinted oncofetal non-coding RNA recently shown tobe the precursor of miR-675. The pathophysiological roles of H19and its mature product miR-675 to carcinogenesis have, however,notbeendefined.Byquantitativereversetranscription–polymerasechain reaction, both H19 and miR-675 were found to be upregu-lated in human colon cancer cell lines and primary humancolorectal cancer (CRC) tissues compared with adjacent non-cancerous tissues. Subsequently, the tumor suppressorretinoblas-toma (RB) was confirmed to be a direct target of miR-675 as themicroRNA suppressed the activity of the luciferase reporter car-rying the 3#-untranslated region of RB messenger RNA that con-tains the miR-675-binding site. Suppression of miR-675 bytransfection with anti-miR-675 increased RB expression and atthe same time, decreased cell growth and soft agar colony forma-tionin human coloncancercells. Reciprocally, enhanced miR-675expression by transfection with miR-675 precursor decreased RBexpression, increased tumor cell growth and soft agar colony for-mation. Moreover, the inverse relationship between the expres-sions of RB and H19/miR-675 was also revealed in human CRCtissues and colon cancer cell lines. Our findings demonstrate thatH19-derived miR-675, through downregulation of its target RB,regulates the CRC development and thus may serve as a potentialtarget for CRC therapy.IntroductionColorectal cancer (CRC) is the third most common cancer worldwidewith an estimated 1 million new cases and a half million deaths eachyear (1). Screening for CRC from curable early stages has the poten-tial to reduce both the incidence and mortality of the disease (2).Although 5 year mortality rates of CRC have slightly declined overthe last three decades, there is still a pressing need to identify newprognostic biomarkers and therapeutic targets for this disease. Fur-thermore, the underlying pathophysiological mechanisms of CRC de-velopment remain elusive (1–4).MicroRNAs (miRNAs) are 19- to 25-nucleotide regulatory non-codingRNAsthatareinitiallyexpressedashairpintranscriptsofprimarymiRNA.TheseprimarymiRNAhairpinsarecleavedbytwoRNAaseIIIenzymes, Drosha and Dicer, to generate mature miRNAs. MiRNAsregulate the expressions of a wide variety of genes by translation re-pression or promoting RNA degradation and are important in the regu-lation of various cellular processes, such as cellular proliferation,differentiation and apoptosis (5–7). To date, .723 human miRNAsare annotatedinthe miRBase registry(miRBaseversion 11.0), but mostof the genes regulated by human miRNAs are not well defined.Dysregulation of a specific spectrum of miRNAs in human malig-nancies is frequently observed. Emerging evidence suggests miRNAsfunction as both tumor suppressors and oncogenes. About 50% ofannotated human miRNAs located at chromosomal regions involvedin loss of heterozygosity, amplification or breakpoints that are asso-ciated with cancers (5,7,8). The miRNAs downregulated in humancancers indicate that they may function as tumor suppressors. Let-7,which targets the oncogene RAS, has shown to be downregulated inBCL2, are downregulated in chronic lymphocytic leukemias (10).Expression levels of miR-143 that targets ERK5 and miR-145 werefound to be decreased in colon cancer (11). In contrast, the miRNAsupregulated in cancers may function as oncogenes. MiR-155 and itshost gene BIC are highly expressed in several types of B-cell lym-phoma (12). The miR-17-92 cluster, which is located on chromosome13q31, is activated by the oncogene c-Myc and is highly expressed inB-cell lymphoma and lung cancer (13). Therefore, the importance ofmiRNAs acting as a new layer of gene regulation in tumorigenesis isemerging.H19 is a paternally imprinted (maternally expressed) oncofetalgene and is located on chromosome 11p15.5, close to the IGF II genelocus. The H19 gene does not encode for a protein but instead codesfor a capped, spliced and polyadenylated 2.7 kb RNA (14–16). H19 ishighly expressed from the early stages of embryogenesis to fetal lifein many organs including the fetal adrenal, liver and placenta but isnearly completely downregulated postnatally (17).Emerging evidence showed that H19 expression was upregulated inmany cancers including CRC (18,19), hepatocellular carcinoma(20), testicular cancer (21), choriocarcinoma (22), esophageal cancer(18), ovarian cancer(23), breast cancer (24) and bladder cancer (25,26),with or without the loss of imprinting. Patients with more H19-positive bladder cancer cells are potentially at higher risk of recurrentdisease (27). In the tumor formed by the injection of choriocarcinomaJar and JEG-3 cells into the nude mice, the H19 RNA level is higherthan those cells before the injection (28). Similarly, the H19 RNAlevel is greatly enhanced in tumor of human bladder carcinoma cellsformed in nude mice (25). The overexpression of H19 in cancertissues hints for its oncogenic function, but the exact underlyingmechanism is still not clear. Recently, H19 was reported to be theprimary miRNA precursor of miR-675 in both human and mice (29).As both H19 and miRNAs are believed to be involved in tumorio-genesis, this prompted us to speculate that the tumoriogenesis processinduced by H19 may be mediated through miR-675. Therefore, in thisstudy, we investigated the pathophysiological roles of H19 and miR-675 in CRC carcinogenesis. Furthermore, using in silico predictionand in vitro functional assays, we confirmed retinoblastoma (RB)protein as a putative direct target of miR-675. This verification ofthe oncogenic function of H19-miR-675-RB in CRC suggests thatthis pathway may serve as the potential target for cancer therapy.Materials and methods