bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of alaryngeal speech using a sound‐producing voice prosthesis in relation to sex and pharyngoesophageal segment tonicity
Authors: van der Torn M. , van Gogh C. D. L. , Verdonck‐de Leeuw I. M. , Festen J. M. , Verkerke G. J. , Mahieu H. F.
Published: February 2006

Background.

A pneumatic artificial sound source incorporated in a regular tracheoesophageal shunt valve may improve alaryngeal voice quality.

Methods.

In 20 laryngectomees categorized for sex and pharyngoesophageal segment tonicity, a prototype sound‐producing voice prosthesis (SPVP) is evaluated for a brief period and compared with their regular tracheoesophageal shunt speech.

Results.

Perceptual voice evaluation by an expert listener and acoustical analysis demonstrate a uniform rise of vocal pitch when using the SPVP. Female laryngectomees with an atonic pharyngoesophageal segment gain vocal strength with the SPVP. Exerted tracheal pressure and airflow rate are equivalent to those required for regular tracheoesophageal shunt valves. However, communicative suitability and speech intelligibility deteriorate by the SPVP for most patients. Tracheal phlegm clogging the SPVP is a hindrance for most patients.

Conclusions.

The SPVP raises vocal pitch. Female laryngectomees with an atonic or severely hypotonic pharyngoesophageal segment can benefit from a stronger voice with the SPVP. © 2005 Wiley Periodicals, Inc. Head Neck 28: 400–412, 2006
Matrix metalloproteases in head and neck cancer
Authors: Rosenthal Eben L. , Matrisian Lynn M.
Published: February 2006

Matrix metalloproteases (MMPs) are a collection of enzymes capable of cleaving extracellular matrix components, growth factors, and cell‐surface receptors. MMPs modulate most aspects of tumorigenesis and are highly expressed in cancer compared with normal tissues. Preclinical studies have demonstrated that head and neck squamous cell carcinomas (HNSCCs) express high levels of MMPs in vivo and that inhibition of these enzymes in vitro and in mouse models decreases invasion and metastasis. However, the clinical trials for MMP inhibitors have failed to demonstrate a significant survival advantage in most cancers. The disparity between preclinical and clinical studies has led to the reevaluation of how MMP functions in cancer and the design of clinical trials for molecularly targeted agents. Mouse model data and analysis of HNSCC tumor specimens suggests that membrane type‐1 MMP (MT1‐MMP) may be a critical enzyme in tumor cell invasion and survival in vivo. This accumulated data provide evidence for development of selective MT1‐MMP inhibitors as therapy in HNSCC. © 2005 Wiley Periodicals, Inc. Head Neck, 2006
The burden of hepatitis C in the United States
Authors: Kim Ray W.
Published: February 2006

According to the third National Health and Nutrition Examination Survey (NHANES), 3.9 million of the U.S. civilian population have been infected with hepatitis C virus (HCV), of whom 2.7 million (74%) have chronic infection. Hepatitis C virus infection is most common among non-Caucasian men, ages 30 to 49 years. Moreover, the prevalence of antibody to hepatitis C virus in groups not represented in the NHANES sample, such as the homeless or incarcerated, may be as high as 40%. The age-adjusted death rate for non-A, non-B viral hepatitis increased from 0.4 to 1.8 deaths per 100,000 persons per year between 1982 and 1999. In 1999, the first year hepatitis C was reported separately, there were 3,759 deaths attributed to HCV, although this is likely an underestimate. There was a 5-fold increase in the annual number of patients with HCV who underwent liver transplantation between 1990 and 2000. Currently, more than one third of liver transplant candidates have HCV. Inpatient care of HCV-related liver disease has also been increasing. In 1998, an estimated 140,000 discharges listed an HCV-related diagnosis, accounting for 2% of discharges from non-federal acute care hospitals in the United States. The total direct health care cost associated with HCV is estimated to have exceeded $1 billion in 1998. Future projections predict a 4-fold increase between 1990 and 2015 in persons at risk of chronic liver disease (i.e., those with infection for 20 years or longer), suggesting a continued rise in the burden of HCV in the United States in the foreseeable future. (Hepatology 2002;36:S30-S34).
Use and interpretation of virological tests for hepatitis C
Authors: Pawlotsky Jean-Michel
Published: February 2006

Four virological markers of hepatitis C virus (HCV) infection are used clinically for management of patients with hepatitis C, namely the HCV genotype, HCV RNA, HCV core antigen, and antibody to HCV (anti-HCV). The diagnosis of acute and chronic hepatitis C is based on both anti-HCV detection using enzyme immunoassays (EIA) and HCV RNA detection using a sensitive molecular biology-based technique. Other virological tools, including HCV genotype determination and HCV RNA quantification, are now used to tailor treatment to the individual patient and to determine its efficacy. This article reviews the kinetics of HCV markers during acute and chronic HCV infection, together with current assays and their practical use in the management of HCV-infected patients. (Hepatology 2002;36:S65-S73).
Hepatocellular carcinoma and hepatitis C in the United States
Authors: El-Serag Hashem B.
Published: February 2006

Chronic infection with hepatitis C virus (HCV) is a major risk factor for development of hepatocellular carcinoma (HCC). In general, HCC develops only after 2 or more decades of HCV infection and the increased risk is restricted largely to patients with cirrhosis or advanced fibrosis. Factors that predispose to HCC among HCV-infected persons include male sex, older age, hepatitis B virus (HBV) coinfection, heavy alcohol intake, and possibly diabetes and a transfusion-related source of HCV infection. Viral factors play a minor role. The likelihood of development of HCC among HCV-infected persons is difficult to determine because of the paucity of adequate long-term cohort studies; the best estimate is 1% to 3% after 30 years. Once cirrhosis is established, however, HCC develops at an annual rate of 1% to 4%. Successful antiviral therapy of patients with HCV-related cirrhosis may reduce the future risk for HCC. The incidence of and mortality caused by all HCC has doubled in the United States over the past 25 years, an increase that has affected all ethnic groups, both sexes, and younger age groups. Given the current prevalence of HCV infection among persons 30 to 50 years of age, the incidence and mortality rates of HCC are likely to double in the United States over the next 10 to 20 years. Future research should focus on improving understanding of the incidence and risk factors for HCC, causes of HCV-related carcinogenesis, means of early detection, and better treatment for HCC. (Hepatology 2002;36:S74-S83).
Screening tests for hepatocellular carcinoma in patients with chronic hepatitis C: A systematic review
Authors: Gebo Kelly A. , Chander Geetanjali , Jenckes Mollie W. , Ghanem Khalil G. , Herlong Franklin H. , Torbenson Michael S. , El-Kamary Samer S. , Bass Eric B.
Published: February 2006

This systematic review addresses the following questions: (1) What is the efficacy of using screening tests for hepatocellular carcinoma (HCC) in improving outcomes in chronic hepatitis C, and (2) what are the sensitivity and specificity of screening tests for HCC in chronic hepatitis C? The search strategy involved searching Medline and other electronic databases between January 1985 and March 2002. Additional articles were identified by reviewing pertinent articles and journals and by querying experts. Articles were eligible for review if they reported original human data from studies of screening tests that used virological, histological, pathologic, or clinical outcome measures. Data collection involved paired reviewers who assessed the quality of each study and abstracted data. One nonrandomized prospective cohort study suggested that HCC was detected earlier and was more often resectable in patients who had twice yearly screening with serum alpha-fetoprotein (AFP) and hepatic ultrasound than in patients who had usual care. Twenty-four studies, which induded patients with chronic hepatitis C or B or both, addressed the sensitivities and specificities of screening tests. They were relatively consistent in showing that the sensitivity of serum AFP for detecting HCC usually was moderately high at 45% to 100%, with a specificity of 70% to 95%, for a threshold of between 10 and 19 ng/mL. The few studies that evaluated screening with ultrasound reported high specificity, but variable sensitivity. In conclusion, screening of patients with chronic hepatitis C with AFP and ultrasound may improve detection of HCC, but studies are needed to determine whether screening improves clinical outcomes. (Hepatology 2002;36:S84-S92).
Sexual activity as a risk factor for hepatitis C
Authors: Terrault Norah A.
Published: February 2006

The accumulated evidence indicates that hepatitis C virus (HCV) can be transmitted by sexual contact but much less efficiently than other sexually transmitted viruses, including hepatitis B virus and human immunodeficiency virus (HIV). However, because sex is such a common behavior and the reservoir of HCV-infected individuals is sizable, sexual transmission of HCV likely contributes to the total burden of infection in the United States. Risk of HCV transmission by sexual contact differs by the type of sexual relationship. Persons in long-term monogamous partnerships are at lower risk of HCV acquisition (0% to 0.6% per year) than persons with multiple partners or those at risk for sexually transmitted diseases (0.4% to 1.8% per year). This difference may reflect differences in sexual risk behaviors or differences in rates of exposure to nonsexual sources of HCV, such as injection drug use or shared razors and toothbrushes. In seroprevalence studies in monogamous, heterosexual partners of HCV-infected, HIV-negative persons, the frequency of antibody-positive and genotype-concordant couples is 2.8% to 11% in Southeast Asia, 0% to 6.3% in Northern Europe, and 2.7% in the United States. Among individuals at risk for sexually transmitted diseases (STDs), the median seroprevalence of antibody to HCV (anti-HCV) is 4% (range, 1.6% to 25.5%). HIV coinfection appears to increase the rate of HCV transmission by sexual contact. Current recommendations about sexual practices are different for persons with chronic HCV infection who are in steady monogamous partnerships versus those with multiple partners or who are in short-term sexual relationships. (Hepatology 2002;36:S99-S105).
Introduction to therapy of hepatitis C
Authors: Lindsay Karen L.
Published: February 2006

Since the 1997 National Institutes of Health Consensus Development Conference on management of hepatitis C there have been several important advances that significantly impact its therapy; notably the availability of sensitive, specific, and standardized assays for identifying hepatitis C virus (HCV) RNA in the serum, the addition of ribavirin to alpha interferon, the pegylation of alpha interferon, and the demonstration that sustained virological response (SVR) is the optimal surrogate endpoint of treatment. Using pegylated interferon and ribavirin, virological response with relapse and nonresponse are less common, but remain poorly understood. Current studies are evaluating nonvirological endpoints of treatment, namely biochemical response and histological response. To date, definitive treatment trials have primarily been conducted in adult patients with elevated aminotransferase levels, clinically compensated chronic liver disease, and no other significant medical disorder. Limited data are available from studies of other patient populations, and the safety of interferon-based treatment has not yet been established in several patient groups. Future research is needed to elucidate the mechanisms of viral response and clearance, to develop effective therapies for interferon nonresponse or intolerance, to define the role of complementary and alternative medicine and other nonspecific therapies, and to develop strategies for the optimal management and treatment of special patient populations who probably represent the majority of persons with chronic hepatitis C in the United States. (Hepatology 2002;36:S114-S120).
Retreatment of patients with chronic hepatitis C
Authors: Shiffman Mitchell L.
Published: February 2006

Significant advances have been made in the treatment of chronic hepatitis C virus (HCV) infection during the past 5 years. As a consequence, there is continuing enthusiasm for retreating patients who did not achieve sustained virological response (SVR) with previous therapy. Retreatment of non-responders to standard interferon monotherapy using interferon and ribavirin has yielded SVR rates of 12% to 15%. Retreatment with peginterferon and ribavirin has been more effective; achieving SVR rates of 34% to 40%. Retreatment of patients who relapsed after interferon monotherapy using standard interferon and ribavirin yielded SVR rates of 47%, whereas retreatment with peginterferon and ribavirin resulted in an SVR rate of about 60%. The major factors associated with a higher likelihood of an SVR after retreatment include previous relapse, previous treatment with interferon monotherapy, HCV genotypes 2 or 3, lower serum levels of HCV RNA, and having a significant decrease in HCV RNA levels during the initial course of therapy. These results help to focus retreatment with peginterferon and ribavirin on subsets of patients who are most likely to benefit. (Hepatology 2002;36:S128-S134).
The role of liver biopsy in chronic hepatitis C
Authors: Dienstag Jules L.
Published: February 2006

The report of the 1997 National Institutes of Health Consensus Development Conference on hepatitis C endorsed pretreatment liver biopsy. We revisit the following questions: Does liver histology help determine the urgency of, and predict the likelihood of response to, antiviral therapy, and can surrogate markers supplant histological assessment? Because the rate of progression of chronic hepatitis C is influenced by baseline histological grade/stage, patients can be stratified into those with moderate to severe hepatitis, who merit imminent therapy, and those with mild hepatitis, in whom therapy can be postponed until more effective/tolerable treatments become available. Less advanced baseline histology has been shown to be an independent predictor of responsiveness to antiviral therapy. Although the predictive value of biopsy is insufficient to withhold therapy from patients with advanced fibrosis, baseline biopsy helps gauge expectations for the outcome of therapy. Reports have been published recently suggesting that laboratory markers can predict distinctions between low-grade fibrosis and therapy-indicating septal fibrosis/cirrhosis. These indices, however, are insufficiently reliable to predict histological distinctions in populations with varying prevalences of fibrosis/cirrhosis or to provide anything more than broad qualitative distinctions, far short of the potential information in a liver biopsy. For most patients, the value of pretreatment liver biopsy outweighs its risks, provides information about the urgency of treatment, and should be retained. Studies to identify noninvasive laboratory markers of histological activity and stage, especially genetic predictors of accelerated disease progression, command a high priority. (Hepatology 2002;36:S152-S160).
Role of liver biopsy in management of chronic hepatitis C: A systematic review
Authors: Gebo Kelly A. , Herlong Franklin H. , Torbenson Michael S. , Jenckes Mollie W. , Chander Geetanjali , Ghanem Khalil G. , El-Kamary Samer S. , Sulkowski Mark , Bass Eric B.
Published: February 2006

This systematic review addresses 2 questions pertinent to the need for pretreatment liver biopsy in patients with chronic hepatitis C: how well do liver biopsy results predict treatment outcomes for chronic hepatitis C? How well do biochemical blood tests and serologic measures of fibrosis predict the biopsy findings in chronic hepatitis C? Medline and other electronic databases were searched from January 1985 to March 2002. Additional articles were sought in references of pertinent articles and recent journals and by querying experts. Articles were eligible for review if they reported original human data from a study that used virological, histological, pathologic, or clinical outcome measures. Paired reviewers assessed the quality of each eligible study and abstracted data. Studies suggested that advanced fibrosis or cirrhosis on initial liver biopsy is associated with a modestly decreased likelihood of a sustained virological response (SVR) to treatment. Also, studies relatively consistently showed that serum aminotransferases have modest value in predicting fibrosis on biopsy; that extracellular matrix tests hyaluronic acid and laminin may have value in predicting fibrosis, and that panels of tests may have the greatest value in predicting fibrosis or cirrhosis. Biochemical and serologic tests were best at predicting no or minimal fibrosis, or at predicting advanced fibrosis/cirrhosis, and were poor at predicting intermediate levels of fibrosis. Thus, evidence suggests that liver biopsy may have some usefulness in predicting efficacy of treatment in patients with chronic hepatitis C, and biochemical blood tests and serologic tests currently have only modest value in predicting fibrosis on liver biopsy. (Hepatology 2002;36:S161-S172).
Children with hepatitis C
Authors: Jonas Maureen M.
Published: February 2006

An estimated 240,000 children in the United States have antibody to hepatitis C virus (HCV) and 68,000 to 100,000 are chronically infected with HCV. Acute HCV infection is rarely recognized in children outside of special circumstances such as a known exposure from an HCV-infected mother or after blood transfusion. Most chronically infected children are asymptomatic and have normal or only mildly abnormal alanine aminotransferase levels. Although the natural history of HCV infection acquired in childhood seems benign in the majority of instances, the infection takes an aggressive course in a proportion of cases leading to cirrhosis and end-stage liver disease during childhood; the factors responsible for a more aggressive course are unidentified. An optimal approach to management of hepatitis C in children would be prevention, particularly of perinatal transmission, which is now the major cause of new cases of hepatitis C in children. Obstetrical factors may be important determinants of transmission, which, if confirmed, should lead to changes in the care of infected women. Therapy of HCV infection in children is also not well defined. There have been no large randomized, controlled trials of therapy in children with chronic hepatitis C. Small heterogeneous studies of interferon monotherapy have reported sustained virological response rates of 35% to 40%. There are few data regarding the use of combination therapy with interferon and ribavirin in children and no information on the use of peginterferon. Clearly, there are important needs for future epidemiologic and clinical research on hepatitis C in childhood. (Hepatology 2002;36:S173-S178).
Treatment of patients with hepatitis C and cirrhosis
Authors: Wright Teresa L.
Published: February 2006

Recommendations for treatment of hepatitis C in patients with cirrhosis are difficult. Few prospective studies have focused on treatment of patients with advanced disease, and response rates appear to be lower and serious side effects more frequent in patients with cirrhosis. In patients with compensated cirrhosis, combination therapy with interferon alfa (3 million units [MU] 3 times a week) and ribavirin (1,000 or 1,200 mg/d) results in a sustained virological response (SVR) in 33% to 41% of patients. Responses to combination therapy are not significantly higher using peginterferon alfa 2a (180 μg/wk; 43%) or peginterferon alfa 2b (1.5 μg/kg/wk; 44%) compared with standard interferon. In using peginterferon in combination therapy, the benefits of once weekly dosing need to be weighed against the higher risks of cytopenias and greater costs with the pegylated formulations. Combination therapy results in some degree of histological improvement even in patients who are virological non-responders. These findings provide the scientific basis for ongoing studies of maintenance therapy with peginterferon to prevent complications of cirrhosis in non-responder patients with hepatitis C. Recommendations for management of decompensated cirrhosis and of recurrent hepatitis C after liver transplantation are difficult because of limitations of data, most of which are derived from uncontrolled case series. Combination therapy is poorly tolerated in both groups and rates of response are low. Thus, while the medical need is great, treatment of patients with decompensated cirrhosis or with recurrent hepatitis C after transplantation should be undertaken cautiously and only within the confines of prospective clinical trials. (Hepatology 2002;36:S185-S194).
Alcohol use and hepatitis C
Authors: Peters Marion G. , Terrault Norah A.
Published: February 2006

Excess alcohol consumption can worsen the course and outcome of chronic hepatitis C. It is important to distinguish between alcohol abuse, which must be treated on its own merits, and the effect of alcohol use on progression, severity, and treatment of hepatitis C. Most studies on the effects of alcohol on hepatitis C have focused on patients with high levels of daily alcohol intake. Indeed, the adverse effects of light and moderate amounts of alcohol intake on hepatitis C virus (HCV) infection have not been clearly shown, and only limited studies have been performed. Sex differences exist in the effect of alcohol on fibrosis as well as on the severity of hepatitis C. Alcohol use has been reported to be associated with lower responses to therapy and, in some studies, higher HCV RNA levels and increased HCV quasi-species. Few studies address the treatment of hepatitis C in the alcoholic individual or determine the effect of continued light or moderate alcohol use on the outcome of treatment response. In summary, many critical questions remain regarding the interactions between alcohol and hepatitis C. Currently, the evidence from the literature shows that heavy alcohol intake worsens the outcome of HCV infection. The literature is inadequate to provide definitive recommendations regarding the effect of light to moderate alcohol use in patients with hepatitis C. (Hepatology 2002;36:S220-S225).
Understudied populations with hepatitis C
Authors: Strader Doris B.
Published: February 2006

Managing patients with hepatitis C virus (HCV) infection consists primarily of antiviral treatment, currently with peginterferon and ribavirin. Unfortunately, treatment recommendations derive largely from trials that have focused on highly selected patient populations. As a consequence of the strict inclusion and exclusion criteria in these studies, more than half of all HCV-infected patients would be ineligible for enrollment. Even among the selected patients enrolled into studies, only 50% achieve a sustained virological response (SVR). Patients not eligible for current therapies include those with mild disease and normal alanine aminotransferase (ALT) levels, patients with advanced and decompensated liver disease, children, the elderly, patients with ongoing or recent alcohol and substance abuse, renal disease, human immunodeficiency virus (HIV) infection, severe psychiatric or neurologic illness, autoimmune disorders, solid organ transplant, and other significant comorbid conditions. Because these patients have been excluded from most clinical trials, little is known about the safety or efficacy of therapy in these populations. The expense and side effects of therapy are also an impediment to treatment of patients who are on public assistance, in prisons, and in institutions. Clearly, new efforts and new approaches are needed to expand the eligibility for antiviral therapy of hepatitis C and make treatment more available for understudied populations with this disease. (Hepatology 2002;36:S226-S236).
SUMO regulates the cytoplasmonuclear transport of its target protein Daxx
Authors: Chen Angela , Wang Ping‐Yao , Yang Yu‐Chih , Huang Yi‐Hsin , Yeh Jeng‐Jung , Chou Yu‐Huai , Cheng Jiin‐Tsuey , Hong Yi‐Ren , Li Steven S.‐L.
Published: February 2006

It is known that Fas death domain‐associated protein (Daxx) possesses both putative nuclear and cytoplasmic functions. However, the nuclear transport mechanism is largely unknown. This study examined the nuclear location signal (NLS) of Daxx and whether the nuclear transport of Daxx was mediated by small ubiquitin‐related modifier (SUMO). Two NLS motifs of Daxx, leucine (L)‐rich nuclear export signal (NES)‐like motif (188IXXLXXLLXL197) and C‐terminal lysine (K) rich NLS2 (amino acids 627–634) motif, were identified and the K630 and K631 on the NLS2 motif were characterized as the major sumoylation sites of Daxx by in vitro sumoylation analysis. Proteins of inactive SUMO (SUMO‐Δ), a sumoylation‐incompetent mutant, and Daxx NLS mutants (Daxx‐NESmut and Daxx NLS2mut) were dispersed in cytoplasm. The cytoplasmic dispersed Daxx mutants could be relocalized to nucleus by cotransfection with active SUMO, but not with inactive SUMO‐Δ, demonstrating the role of SUMO on regulating the cytoplasmonuclear transport of Daxx. However, inactive SUMO‐Δ could also be relocalized to nucleus during cotransfection with wild‐type Daxx, suggesting that SUMO regulation of the cytoplasmonuclear transport of its target protein Daxx does not need covalent modification. This study shows that cytoplasmic SUMO has a biological role in enhancing the cytoplasmonuclear transport of its target protein Daxx and it may be done through the non‐sumoylation interactions. J. Cell. Biochem. 98: 895–911, 2006. © 2006 Wiley‐Liss, Inc.
Role of soluble ceruloplasmin in iron uptake by midbrain and hippocampus neurons
Authors: Ke Ya , Ho Kwokping , Du Jinrong , Zhu Li , Xu Youjia , Wang Qin , Wang Chen Yuen , Li Lianzhi , Ge Xiaohu , Chang Yang Zhong , Qian Zhong Ming
Published: February 2006

Ceruloplasmin (CP) is essential for brain iron homeostasis. However, its precise function in brain iron transport has not been definitely determined. In this study, we investigated the effects of soluble CP on iron influx and efflux in primary neuronal culture from the midbrain (the substantia nigra and striatum) and the hippocampus. Our data showed that low concentrations of CP (2, 4, 8 µg/ml) can promote iron influx into iron‐deficient neurons, but not the neurons with normal iron status. The same concentrations of CP had no effect on iron efflux from iron‐sufficient and normal‐iron neurons. Contrary to our expectation, we did not find any regional difference in the effects of CP on iron influx as well as efflux in neurons. The changes in quenching (iron influx) and also dequenching (iron efflux) of intracellular fluorescence, induced by the addition of CP with iron, in the midbrain neurons were no different from those in the hippocampus neurons. The data showed that soluble CP has a role in iron uptake by iron‐deficient brain neurons under our experimental conditions. The physiological significance of the results forms the focus for future work. J. Cell. Biochem. 98: 912–919, 2006. © 2006 Wiley‐Liss, Inc.
Identification of nuclear localization signal that governs nuclear import of BRD7 and its essential roles in inhibiting cell cycle progression
Authors: Zhou Ming , Liu Huaying , Xu Xiaojie , Zhou Houde , Li Xiaoling , Peng Cong , Shen Shourong , Xiong Wei , Ma Jian , Zeng Zhaoyang , Fang Songqing , Nie Xinmin , Yang Yixin , Zhou Jie , Xiang Juanjuan , Cao Li , Peng Shuping , Li Shufang , Li Guiyuan
Published: February 2006

BRD7, a novel bromodomain gene, is identified to be associated with nasopharyngeal carcinoma (NPC). Decreased or loss of expression of BRD7 was detected in NPC biopsies and cell lines. Overexpression of BRD7 could inhibit NPC cell growth and arrest cells in cell cycle by transcriptionally regulating some important molecules involved in ras/MEK/ERK and Rb/E2F pathway, and downregulate the promoter activity of E2F3. In the present study, the subcellular localization of BRD7 was investigated. It was found that BRD7 was mainly localized in nucleus without distinct cell‐specific difference between COS7 and HNE1. Furthermore, a functional nuclear localization signal (NLS) sequence ranging from amino acid 65 to 96 was identified and characterized. The NLS is composed of a cluster of four bipartite nuclear targeting sequences, which are tightly linked and extremely overlapped. We found that whether the entire NLS or the four bipartite nuclear targeting sequences could respectively determine the nuclear import of green fluorescent protein (GFP). The most important is that NLS‐deleted BRD7 shifted the nuclear localization to be mostly in cytoplasm, and failed or reduced to negatively regulate the expression of cell cycle related molecules, cyclin D1 and E2F3, and cell cycle progression from G1 to S phase. In conclusion, NLS is an essential motif affecting BRD7 nuclear distribution, and the nuclear localization of BRD7 is critical for the expression of cell cycle related molecules and cell biological function. J. Cell. Biochem. 98: 920–930, 2006. © 2006 Wiley‐Liss, Inc.
The vertebrate E1/U17 small nucleolar ribonucleoprotein particle
Authors: Eliceiri George L.
Published: February 2006

Each of the many different box H/ACA ribonucleoprotein particles (RNPs) present in eukaryotes and archaea consists of four common core proteins and one specific H/ACA small RNA, which bears the sequence elements H (ANANNA) and ACA. Most of the H/ACA RNPs are small nucleolar RNPs (snoRNPs), which are localized in nucleoli, and are one of the two major classes of snoRNPs. Most H/ACA RNPs direct pseudouridine synthesis in pre‐rRNA and other RNAs. One H/ACA small nucleolar RNA (snoRNA), vertebrate E1/U17 (snR30 in yeast), is required for pre‐rRNA cleavage processing that generates mature 18S rRNA. E1 snoRNA is encoded in introns of protein‐coding genes, and the evidence suggests that human E1 RNA undergoes uridine insertional RNA editing. The vertebrate E1 RNA consensus secondary structure shows several features that are absent in other box H/ACA snoRNAs. The available UV‐induced RNA‐protein crosslinking results suggest that the E1 snoRNP is asymmetrical in vertebrate cells, in contrast to other H/ACA snoRNPs. The vertebrate E1 snoRNP in cells is surprisingly complex: (i) E1 RNA contacts directly and specifically several proteins which do not appear to be any of the H/ACA RNP four core proteins; and (ii) multiple E1 RNA sites are needed for E1 snoRNP formation, E1 RNA stability, and E1 RNA–protein direct interactions. J. Cell. Biochem. 98: 486–495, 2006. © 2006 Wiley‐Liss, Inc.
Role of protein phosphatase 2A in the regulation of endothelial cell cytoskeleton structure
Authors: Tar Krisztina , Csortos Csilla , Czikora Istvan , Olah Gabor , Ma Shwu‐Fan , Wadgaonkar Raj , Gergely Pal , Garcia Joe G.N. , Verin Alexander D.
Published: February 2006

Our recently published data suggested the involvement of protein phosphatase 2A (PP2A) in endothelial cell (EC) barrier regulation (Tar et al. [2004] J Cell Biochem 92:534–546). In order to further elucidate the role of PP2A in the regulation of EC cytoskeleton and permeability, PP2A catalytic (PP2Ac) and A regulatory (PP2Aa) subunits were cloned and human pulmonary arterial EC (HPAEC) were transfected with PP2A mammalian expression constructs or infected with PP2A recombinant adenoviruses. Immunostaining of PP2Ac or of PP2Aa + c overexpressing HPAEC indicated actin cytoskeleton rearrangement. PP2A overexpression hindered or at least dramatically reduced thrombin‐ or nocodazole‐induced F‐actin stress fiber formation and microtubule (MT) dissolution. Accordingly, it also attenuated thrombin‐ or nocodazole‐induced decrease in transendothelial electrical resistance indicative of barrier protection. Inhibition of PP2A by okadaic acid abolished its effect on agonist‐induced changes in EC cytoskeleton; this indicates a critical role of PP2A activity in EC cytoskeletal maintenance. The overexpression of PP2A significantly attenuated thrombin‐ or nocodazole‐induced phosphorylation of HSP27 and tau, two cytoskeletal proteins, which potentially could be involved in agonist‐induced cytoskeletal rearrangement and in the increase of permeability. PP2A‐mediated dephosphorylation of HSP27 and tau correlated with PP2A‐induced preservation of EC cytoskeleton and barrier maintenance. Collectively, our observations clearly demonstrate the crucial role of PP2A in EC barrier protection. J. Cell. Biochem. 98: 931–953, 2006. © 2006 Wiley‐Liss, Inc.
Paneling human thyroid cancer cell lines for candidate proteins for targeted anti‐angiogenic therapy
Authors: Hoffmann Sebastian , Wunderlich Anette , Celik Ilhan , Maschuw Katja , Hassan Iyad , Hofbauer Lorenz C. , Zielke Andreas
Published: February 2006

Tumor angiogenesis is believed to result from an imbalance of pro‐ and anti‐angiogenic factors, some of which are candidates for targeted therapy. Such therapy has raised hopes for patients with undifferentiated thyroid carcinomas, who are facing a grave prognosis with a survival of only months. In this study, in vivo growth of xenografted human thyroid carcinomas unexpectedly responded quite differently to neutralizing anti‐vascular endothelial growth factor (VEGF) antibody. In particular, lasting inhibition as well as accelerated growth occurred after treatment. Consequently, a panel of anti‐angiogenic factors was addressed in a representative sample of thyroid carcinoma lines. VEGF, fibroblast growth factor (FGF‐2), and endostatin were demonstrated by Western blotting and EIA, whereas PDGF‐A, PDGF‐B, and IL‐6 were negative. Quantification of VEGF, FGF‐2, and endostatin revealed a wide range of concentrations from 500 to 4,200 pg/ml VEGF, 5 to 60 pg/ml FGF‐2, and 50 to 300 pg/ml endostatin, not related to a particular histologic thyroid carcinoma background. Angiostatin (kringles 1–3) was detected in all, but one of the cell lines. Finally, aaATIII was confirmed in FTC133 cells. These data highlight the complex regulation of angiogenesis in thyroid carcinoma cell lines and suggest that the array of angiogenic factors differs markedly between individual cell lines. For the first time, angiostatin, endostatin, and possibly also aaATIII are identified as novel candidate regulators of angiogenesis in thyroid carcinoma cells. J. Cell. Biochem. 98: 954–965, 2006. © 2006 Wiley‐Liss, Inc.
Gap junction communications influence upon fibroblast synthesis of Type I collagen and fibronectin
Authors: Ehrlich H. Paul , Sun Bonnie , Saggers Gregory C. , Kromath Fatuma
Published: February 2006

In rats polyvinyl alcohol sponge subcutaneous implants treated with gap junctional intercellular communications (GJIC) uncouplers showed reduced deposition of connective tissue. Do uncouplers inhibit the synthesis and deposition of a new connective tissue by fibroblasts? Confluent human dermal fibroblasts in serum‐free medium received either endosulfan or oleamide, GJIC uncouplers. Collected media were subjected to Dot Blot analysis for native Type I collagen and fibronectin. Uncoupler‐treated fibroblasts released less Type I collagen, while there was no change in fibronectin release. Collagen synthesis was restored to normal, when the uncouplers were removed, showing that these uncouplers were reversible and not toxic to cells. Northern blot analysis revealed procollagen α1 (I) mRNA was minimally affected by endosulfan. Oleamide‐treated 17‐day chick embryo calvaria explants were incubated with Type I collagen antibody, frozen, cryosectioned, and then subjected to rhodamine (Rh) tagged anti‐mouse‐IgG antibody, to detect newly deposited Type I collagen. Fluorescent antibody‐collagen complexes were localized on the periphery of cells in control calvaria, but absent around cells in oleamide‐treated calvaria. GJIC optimize collagen synthesis but not fibronectin synthesis. The lack of connective tissue deposited in granulation tissues treated with uncouplers appears related to the inhibition of collagen synthesis. These findings suggest that altering GJIC might control collagen deposition in scarring. J. Cell. Biochem. 98: 735–743, 2006. © 2006 Wiley‐Liss, Inc.
Theoretical mechanistic study on the radical‐molecule reaction of CHCl2/CCl3 with NO2
Authors: Zhang Jia‐Xu , Li Ze‐Sheng , Liu Jing‐Yao , Sun Chia‐Chung
Published: February 2006

The radical‐molecule reaction mechanism of CHCl2 and CCl3 with NO2 have been explored theoretically at the B3LYP/6‐311G(d,p) and MC‐QCISD (single‐point) levels. For the singlet potential energy surface (PES) of CHCl2 + NO2 reaction, the association of CHCl2 with NO2 was found to be a barrierless carbon‐to‐nitrogen approach forming an energy‐rich adduct a (HCl2CNO2) followed by isomerization to b1 (trans–cis‐HCl2CONO), which can easily interconvert to b2, b3, and b4. Subsequently, the most feasible pathway is the 1,3‐chlorine migration associated with NO1 bond cleavage of b1 leading to P1 (CHClO + ClNO). The second competitive pathway is the 1,4‐chlorine migration along with NO1 bond rupture of b4 giving rise to P2 (CHClO + ClON). Moreover, some of P1 and P2 can further dissociate to give P6 (CHClO + Cl + NO). The lesser followed competitive channel is the 1,3‐H‐shift from C to N atom along with NO1 bond rupture of b1 to form P3 (CCl2O + HNO). The concerted 1,4‐H‐shift accompanied by NO1 bond fission of b3 to product P4 (CCl2O + HON) is even much less feasible. For the singlet PES of CCl3 + NO2 reaction, the only primary product is found to be P1 (CCl2O + ClNO), which can lead to P2 (CCl2O + Cl + NO) via dissociation of ClNO. The obtained major products CHClO and CCl2O for CHCl2 + NO2 and CCl3 + NO2 reactions, respectively, are in good agreement with kinetic detection in experiment. Compared with the singlet pathways, the triplet pathways may have less contributions to both reactions. Because the rate‐determining transition state involved in the feasible pathways lie above the reactants R, the title reactions may be important in high‐temperature processes. The similarities and discrepancies among the CHnCl3−n + NO2 (n == 0–2) reactions are discussed in terms of the substitution effect. The present study may be helpful for further experimental investigation of the title reactions. © 2006 Wiley Periodicals, Inc. J Comput Chem 27: 661–671, 2006
Repression of HIP/RPL29 expression induces differentiation in colon cancer cells
Authors: Liu Jian‐Jun , Huang Bao Hua , Zhang Jinqiu , Carson Daniel D. , Hooi Shing Chuan
Published: February 2006

We had previously shown that the expression of heparin/heparan sulfate interacting protein/ribosomal protein L29 (HIP/RPL29) was upregulated in colon cancer tissues. The present study investigated the role of HIP/RPL29 in differentiation in colon cancer cells. Inducing cellular differentiation in HT‐29 cells by both sodium butyrate and glucose deprivation resulted in a significant downregulation of HIP/RPL29 expression. The β‐catenin/Tcf‐4 pathway is the most important pathway controlling the switch between cellular differentiation and proliferation in intestinal epithelial cells. Inducing differentiation by dominant‐negative inhibition of the β‐catenin/Tcf‐4 complexes in LS174T cells also resulted in downregulation of HIP/RPL29. To determine whether a lower expression of HIP/RPL29 could induce differentiation in cancer cells, small interfering RNA (siRNA) targeting HIP/RPL29 was transfected into LS174T cells. The resultant knockdown of HIP/RPL29 expression induced cellular differentiation, as shown by the increased expression of two known markers of differentiation in LS174T cells, galectin‐4 and mucin‐2. In addition, the differentiation process induced by repression of HIP/RPL29 expression was accompanied by the upregulation of p21 and p53. In conclusion, HIP/RPL29 plays a role in the cellular differentiation process in colon cancer cells. The differentiation process is at least partially mediated by the upregulation of p21 and p53 pathways. J. Cell. Physiol. 207: 287–292, 2006. © 2006 Wiley‐Liss, Inc.
Morphometric discrimination of early life stage Lampetra tridentata and L. richardsoni (Petromyzonidae) from the Columbia River Basin
Authors: Meeuwig Michael H. , Bayer Jennifer M. , Reiche Rebecca A.
Published: February 2006

The effectiveness of morphometric and meristic characteristics for taxonomic discrimination of Lampetra tridentata and L. richardsoni (Petromyzonidae) during embryological, prolarval, and early larval stages (i.e., age class 1) were examined. Mean chorion diameter increased with time from fertilization to hatch and was significantly greater for L. tridentata than for L. richardsoni at 1, 8, and 15 days postfertilization. Lampetra tridentata larvae had significantly more trunk myomeres than L. richardsoni; however, trunk myomere numbers were highly variable within species and deviated from previously published data. Multivariate examinations of prolarval and larval L. tridentata (7.2–11.0 mm; standard length) and L. richardsoni (6.6–10.8 mm) were conducted based on standard length and truss element lengths established from eight homologous landmarks. Principal components analysis indicated allometric relationships among the morphometric characteristics examined. Changes in body shape were indicated by groupings of morphometric characteristics associated with body regions (e.g., oral hood, branchial region, trunk region, and tail region). Discriminant function analysis using morphometric characteristics was successful in classifying a large proportion (>94.7%) of the lampreys sampled. J. Morphol. © 2006 Wiley‐Liss, Inc.
The assessment of communities of practice
Authors: Verburg Robert M. , Andriessen J. H. Erik
Published: February 2006

This paper introduces the Community Assessment Toolkit (CAT) as a method for the assessment of Communities of Practice (CoPs) and provides an overview of its construction and applicability. It shows that the methodology is based on current theories with regard to CoPs and group dynamics. The method was also tested in practice through a pilot and a study among members of 7 communities of practice (N=271) in order to enable reliability tests and scale analysis. The method is unique in the sense that it provides feedback on the overall performance of CoPs on the individual, group and organizational level. The systematic nature of the CAT questionnaire enables comparisons between communities both within and between organizations. The CAT may be used for further scientific research into CoPs as well as for the analysis of community effectiveness for companies. Copyright © 2006 John Wiley & Sons, Ltd.
Valuing knowledge sharing in Lafarge
Authors: Perrin Alexandre , Vidal Pascal , McGill Jennifer
Published: February 2006

This paper describes the detailed process of a knowledge sharing strategy at Lafarge, a global player in the construction materials industry. The case study explains why this company uses such a strategy to create value for stakeholders, provide a local access to know‐how and build a knowledge sharing culture among divisions. It argues that a well‐articulated approach of a knowledge sharing strategy consists in creating a knowledge portfolio, supporting a knowledge management structure, providing tools for collaboration and nurture a culture of knowledge sharing through awards. At the end, we discuss the lessons learned by the Corporate Knowledge Manager on this strategy and we study how she can quantify the value brought by its action. In a whole, this paper gives insights of critical issues in moving a global company towards a knowledge‐sharing organization. Copyright © 2006 John Wiley & Sons, Ltd.
Knowledge asset value spiral: linking knowledge assets to company's performance
Authors: Carlucci Daniela , Schiuma Giovanni
Published: February 2006

In today's economy, more and more organisations are realising that they must explicitly manage their knowledge resources to acquire and maintain their competitive advantage. For this reason, managers need to better understand how they can identify and evaluate existing knowledge resources within an organisation and how to manage them in order to achieve competitive advantage.

Many organisations frequently embark on Knowledge Management (KM) initiatives without a clear idea of what business benefits they could expect. This is mainly due to lack of understanding of the links between KM and company's business performance. Understanding these links supports the validation of KM investment and can help explain what knowledge should be managed within an organisation to achieve performance improvement. It appears from literature analysis, that there is not straightforward link between KM and company's performance but rather a complex relationship. In such a prospect, the main research question that has inspired this study is: ‘How can an organisation plan and evaluate a KM initiative designed to improve company's performances?’ On the base of this question, this paper provides a framework—the Knowledge Assets Value Spiral (KAVS)—which focuses on how to apply KM initiatives in a step by step process to achieve company's performance improvements. The framework provides guidelines to plan, implement and evaluate KM initiatives that are linked to performance objectives. It is illustrated how organisations can identify their key knowledge assets as well as their interdependencies and better understand their role in causal dynamics in company's value delivering. The application of the Analytic Hierarchy Process (AHP) method is proposed and a case example describing the application of the framework is illustrated. Copyright © 2006 John Wiley & Sons, Ltd.
Centralized versus peer‐to‐peer knowledge management systems
Authors: Maier Ronald , Hädrich Thomas
Published: February 2006

The term knowledge management system (KMS) has been used widely to denote information and communication technologies in support of knowledge management. However, so far investigations about the notion of KMS, their functions and architecture as well as the differences to other types of systems remain on an abstract level. This paper reviews the literature on KMS and distills a number of characteristics concerning the specifics of knowledge to be managed, the platform metaphor, advanced services, KM instruments, supported processes, participants and goals of their application. The paper then presents two ideal architectures for KMS, a centralized and a peer‐to‐peer architecture, discusses their differences with the help of two example systems and suggests that each of these architectures fits a different type of KM initiative. Copyright © 2006 John Wiley & Sons, Ltd.
Cognitive function in multiple system atrophy of the cerebellar type
Authors: Bürk Katrin , Daum Irene , Rüb Udo
Published: February 2006

Dementia represents an exclusion criterion for the diagnosis of multiple system atrophy (MSA), but there have been reports of fronto‐executive dysfunction in patients with MSA of the striatonigral type (MSA‐P). To study the cognitive profile of MSA, 20 patients with MSA of the cerebellar type (MSA‐C) were subjected to an extensive neuropsychological test battery comprising tests for IQ, attention, verbal and visuospatial memory, as well as executive function. There was evidence for impaired verbal memory and verbal fluency. Test performance was not related to the severity of motor disability. Regarding the similar cognitive syndrome of MSA‐P, the otherwise subclinical problems in MSA‐C result from subcortical rather than from cerebellar dysfunction. © 2006 Movement Disorder Society