Antinuclear antibodies (ANA) in chronic hepatitis C virus infection: correlates of positivity and clinical relevance.

We examined correlates of antinuclear antibody (ANA) positivity (ANA+) in individuals with chronic hepatitis C virus (HCV) infection and the effect of positivity on clinical outcome of HCV. Pretreatment sera from 645 patients from three centres in Sweden (n = 225), the UK (n = 207) and Italy (n = 213) were evaluated by indirect immunofluorescence on Hep-2 cells for ANA pattern and titre by a single laboratory. Liver biopsies were all scored by one pathologist. A total of 258 patients were subsequently treated with interferon monotherapy. There was a significant difference in the prevalence of ANA (1:40) by geographic location: Lund 4.4%, London 8.7%, Padova 10.3% [odds ratio (OR) = 0.66; 95% CI: 0.46-0.94; P = 0.023]. Duration of HCV infection, age at infection, current age, route of infection, viral genotype, alcohol consumption, fibrosis stage and inflammatory score were not correlated with ANA+ or ANA pattern. Female gender was correlated with ANA+ and this association persisted in multivariable analyses (OR = 3.0; P = 0.002). Increased plasma cells were observed in the liver biopsies of ANA-positive individuals compared with ANA-negative individuals, while a trend towards decreased lymphoid aggregates was observed [hazard ratio (HR) = 9.0, P = 0.037; HR = 0.291, P = 0.118, respectively]. No correlations were observed between ANA positivity and nonresponse to therapy (OR = 1.4; P = 0.513), although ANA+ was correlated with faster rates of liver fibrosis, this was not statistically significant (OR = 1.8; P = 0.1452). Low titre ANA+ should not be a contraindication for interferon treatment. Our observation of increased plasma cells in ANA+ biopsies might suggest B-cell polyclonal activity with a secondary clinical manifestation of increased serum immunoglobulins

Risk factors for acquisition of hepatitis C virus infection: a case series and potential implications for disease surveillance

Background: Transmission of hepatitis C vims ( HCV) is strongly associated with use of contaminated blood products and injection drugs. Other "non-parental" modes of transmission including sexual activity have been increasingly recognized. We examined risk factors for acquiring HCV in patients who were referred to two tertiary care centers and enrolled in an antiviral therapy protocol. Methods: Interviews of 148 patients were conducted apart from their physician evaluation using a structured questionnaire covering demographics and risk factors for HCV acquisition. Results: Risk factors ( blood products, injection/intranasal drugs, razor blades/toothbrushes, body/ear piercing, occupational exposure, sexual activity) were identified in 141 (95.3%) of participants; 23 (15.5%) had one ( most frequently blood or drug exposure), 41 (27.7%) had two, and 84 (53.4%) had more than two risk factors. No patient reported sexual activity as a sole risk factor. Body piercing accounted for a high number of exposures in women. Men were more likely to have exposure to street drugs but less exposure to blood products than women. Blood product exposure was less common in younger than older HCV patients. Conclusion: One and often multi le risk factors could be identified in nearly all HCV-infected patients seen in a referral practice. None named sexual transmission as the sole risk factor. The development of a more complete profile of factors contributing to transmission of HCV infection may assist in clinical and preventive efforts. The recognition of the potential presence of multiple risk factors may have important implications in the a roach to HCV surveillance, and particularly the use of hierarchical algorithms in the study of risk factors

Regulation of PTP1D mRNA by Peptide Growth Factors in the Human Endometrial Cell Line HEC-1-A

Objective: To assess, in the human endometrial cell line HEC-1-A, the presence of protein tyrosine phosphatase 1D (PTDP1D) and the possible regulation of its mRNA expression by mitogens such as forskolin (an agent that increases intracellular cyclic adenosine monophosphate [cAMP] levels), epidermal growth factor (EGF), and insulin-like growth factor-I (IGF-I). Methods: Cells were grown to confluence and maintained in serum-free media for 24 hours before treatment. Cells were exposed to forskolin, EGF, and IGF-I for increasing time periods (0, 1, 3, 6, and 24 hours), and PTP1D mRNA expression was determined by Northern blot analysis. In addition, cells were incubated with increasing doses of forskolin (final concentrations: 1, 5, 10, 20, and 30 μmol/L0 for 6 hours. Results: When treated with the various mitogens, cells increased their stimulation of PTP1D mRNA expression in a time- and dose-dependent fashion. Specifically, forskolin, EGF, and IGF-I induced maximal mRNA expression at 6, 3, and 6 hours, respectively. Expression induced by forskolin, EGF, and IGF-I was five, three, and six times control levels, respectively. At a dose of 10 μmol/L, forskolin induced PTP1D mRNA expression almost two times higher than control values. Conclusion: These data suggest that in human endometrial carcinomas, cAMP, EGF, and IGF-I may regulate the expression of PTP1D mRNA, which may, in turn, play a role in uncontrolled cell proliferation and neoplastic transformation.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68928/2/10.1177_107155769700400608.pd

Trends of increase in western medical services in traditional medicine hospitals in china

Background: Compare changes in types of hospital service revenues between traditional Chinese medicine (TCM) hospitals and Western-medicine based general hospitals. Methods: 97 TCM hospitals and 103 general hospitals were surveyed in years of 2000 and 2004. Six types of medical service revenue between the two types of hospitals were compared overtime. The national statistics from 1999 to 2008 were also used as complementary evidence. Results: For TCM hospitals, the percentage of service revenue from Western medicine increased from 44.3% to 47.4% while the percentage of service revenue from TCM declined from 26.4% to 18.8% from 1999 to 2004. Percentages of revenue from laboratory tests and surgical procedures for both types of hospitals increased and the discrepancy between the two types of hospitals was narrowed from 1999 to 2004. For TCM hospitals, revenues from laboratory tests increased from 3.64% to 5.06% and revenues from surgical procedures increased from 3.44% to 7.02%. General hospitals\u27 TCM drug revenue in outpatient care declined insignificantly from 5.26% to 3.87%, while the decline for the TCM hospitals was significant from 19.73% to 13.77%. The national statistics from 1999 to 2008 showed similar trends that the percentage of revenue from Western medicine for TCM hospitals increased from 59.6% in 1999 to 62.2% in 2003 and 66.1% in 2008 while the percentage of revenue from TCM for TCM hospitals decreased from 18.0% in 1999, 15.4% in 2003, and 13.7% in 2008. Conclusion: Western medicine has become a vital revenue source for TCM hospitals in the current Chinese health care environment where government subsidies to health care facilities have significantly declined. Policies need to encourage TCM hospitals to identify their own special and effective services, improve public perception, increase demand, strengthen financial sources, and ultimately make contributions to preserving one of the national treasures

Risk factors for acquisition of hepatitis C virus infection: a case series and potential implications for disease surveillance

BACKGROUND: Transmission of hepatitis C vims (HCV) is strongly associated with use of contaminated blood products and injection drugs. Other "non-parental" modes of transmission including sexual activity have been increasingly recognized. We examined risk factors for acquiring HCV in patients who were referred to two tertiary care centers and enrolled in an antiviral therapy protocol. METHODS: Interviews of 148 patients were conducted apart from their physician evaluation using a structured questionnaire covering demographics and risk factors for HCV acquisition. RESULTS: Risk factors (blood products, injection/intranasal drugs, razor blades/ toothbrushes, body/ear piercing, occupational exposure, sexual activity) were identified in 141 (95.3%) of participants; 23 (15.5%) had one (most frequently blood or drug exposure), 41 (27.7%) had two, and 84 (53.4%) had more than two risk factors. No patient reported sexual activity as a sole risk factor. Body piercing accounted for a high number of exposures in women. Men were more likely to have exposure to street drugs but less exposure to blood products than women. Blood product exposure was less common in younger than older HCV patients. CONCLUSION: One and often multiple risk factors could be identified in nearly all HCV-infected patients seen in a referral practice. None named sexual transmission as the sole risk factor. The development of a more complete profile of factors contributing to transmission of HCV infection may assist in clinical and preventive efforts. The recognition of the potential presence of multiple risk factors may have important implications in the approach to HCV surveillance, and particularly the use of hierarchical algorithms in the study of risk factors

Tumor Necrosis Factor-Alpha G308α Gene Polymorphism and Essential Hypertension: A Meta-Analysis Involving 2244 Participants

BACKGROUND: The tumor necrosis factor-alpha (TNFα) G308A gene polymorphism has been implicated in susceptibility to essential hypertension (EH), but study results are still controversial. OBJECTIVE AND METHODS: The present meta-analysis is performed to investigate the relationship between the TNFα G308A gene polymorphism and EH. Electronic databases were searched and seven separate studies on the association of the TNF α G308A gene polymorphism with EH were analyzed. The meta-analysis involved 1092 EH patients and 1152 controls. The pooled odds ratios (ORs) and their corresponding 95% confidence interval (CI) were calculated by a fixed or random effect model. RESULTS: A significant relationship between the TNFα G308A gene polymorphism and EH was found in an allelic genetic model (OR: 1.45, 95% CI: 1.17 to 1.80, P = 0.0008), a recessive genetic model (OR: 3.181, 95% CI: 1.204 to 8.408, P = 0.02), and a homozygote model (OR: 3.454, 95% CI: 1.286 to 9.278, P = 0.014). No significant association between them was detected in both a dominant genetic model (OR: 1.55, 95% CI: 0.99 to 2.42, P = 0.06) or a heterozygote genetic model (OR: 1.45, 95% CI: 0.90 to 2.33, P = 0.13). CONCLUSION: The TNFα G308A gene polymorphism is associated with EH susceptibility

The GOGREEN survey: The environmental dependence of the star-forming galaxy main sequence at 1.0<z<1.51.0<z<1.5

We present results on the environmental dependence of the star-forming galaxy main sequence in 11 galaxy cluster fields at $1.0 < z < 1.5$ from the Gemini Observations of Galaxies in Rich Early Environments Survey (GOGREEN) survey. We use a homogeneously selected sample of field and cluster galaxies whose membership is derived from dynamical analysis. Using [OII]-derived star formation rates (SFRs), we find that cluster galaxies have suppressed SFRs at fixed stellar mass in comparison to their field counterparts by a factor of 1.4 $\pm$ 0.1 ($\sim3.3\sigma$) across the stellar mass range: $9.0 < \log(M_{*} /M_{\odot}) < 11.2$. We also find that this modest suppression in the cluster galaxy star-forming main sequence is mass and redshift dependent: the difference between cluster and field increases towards lower stellar masses and lower redshift. When comparing the distribution of cluster and field galaxy SFRs to the star-forming main sequence, we find an overall shift towards lower SFRs in the cluster population, and note the absence of a tail of high SFR galaxies as seen in the field. Given this observed suppression in the cluster galaxy star-forming main sequence, we explore the implications for several scenarios such as formation time differences between cluster and field galaxies, and environmentally-induced star formation quenching and associated timescales

Immunohistochemical expression of insulin-like growth factor binding protein-3 in invasive breast cancers and ductal carcinoma in situ: implications for clinicopathology and patient outcome

INTRODUCTION: Insulin-like growth factor binding protein-3 (IGFBP-3) differentially modulates breast epithelial cell growth through insulin-like growth factor (IGF)-dependent and IGF-independent pathways and is a direct (IGF-independent) growth inhibitor as well as a mitogen that potentiates EGF (epidermal growth factor) and interacts with HER-2. Previously, high IGFBP-3 levels in breast cancers have been determined by enzyme-linked immunosorbent assay and immunoradiometric assay methods. In vitro, IGFBP-3's mechanisms of action may involve cell membrane binding and nuclear translocation. To evaluate tumour-specific IGFBP-3 expression and its subcellular localisation, this study examined immunohistochemical IGFBP-3 expression in a series of invasive ductal breast cancers (IDCs) with synchronous ductal carcinomas in situ (DCIS) in relation to clinicopathological variables and patient outcome. METHODS: Immunohistochemical expression of IGFBP-3 was evaluated with the sheep polyclonal antiserum (developed in house) with staining performed as described previously. RESULTS: IGFBP-3 was evaluable in 101 patients with a variable pattern of cytoplasmic expression (positivity of 1+/2+ score) in 85% of invasive and 90% of DCIS components. Strong (2+) IGFBP-3 expression was evident in 32 IDCs and 40 cases of DCIS. A minority of invasive tumours (15%) and DCIS (10%) lacked IGFBP-3 expression. Nuclear IGFBP-3 expression was not detectable in either invasive cancers or DCIS, with a consistent similarity in IGFBP-3 immunoreactivity in IDCs and DCIS. Positive IGFBP-3 expression showed a possible trend in association with increased proliferation (P = 0.096), oestrogen receptor (ER) negativity (P = 0.06) and HER-2 overexpression (P = 0.065) in invasive tumours and a strong association with ER negativity (P = 0.037) in DCIS. Although IGFBP-3 expression was not an independent prognosticator, IGFBP-3-positive breast cancers may have shorter disease-free and overall survivals, although these did not reach statistical significance. CONCLUSIONS: Increased breast epithelial IGFBP-3 expression is a feature of tumorigenesis with cytoplasmic immunoreactivity in the absence of significant nuclear localisation in IDCs and DCIS. There are trends between high levels of IGFBP-3 and poor prognostic features, suggesting that IGFBP-3 is a potential mitogen. IGFBP-3 is not an independent prognosticator for overall survival or disease-free survival, to reflect its dual effects on breast cancer growth regulated by complex pathways in vivo that may relate to its interactions with other growth factors

A uniform procedure for the purification of CDK7/CycH/MAT1, CDK8/CycC and CDK9/CycT1

We have established a uniform procedure for the expression and purification of the cyclin-dependent kinases CDK7/CycH/MAT1, CDK8/CycC and CDK9/CycT1. We attach a His(6)-tag to one of the subunits of each complex and then co-express it together with the other subunits in Spodoptera frugiperda insect cells. The CDK complexes are subsequently purified by Ni(2+)-NTA and Mono S chromatography. This approach generates large amounts of active recombinant kinases that are devoid of contaminating kinase activities. Importantly, the properties of these recombinant kinases are similar to their natural counterparts (Pinhero et al. 2004, Eur J Biochem 271:1004-14). Our protocol provides a novel systematic approach for the purification of these three (and possibly other) recombinant CDKs

The GOGREEN survey: Post-infall environmental quenching fails to predict the observed age difference between quiescent field and cluster galaxies at z>1

We study the star formation histories (SFHs) and mass-weighted ages of 331 UVJ-selected quiescent galaxies in 11 galaxy clusters and in the field at 11 has been driven by different physical processes than those at play at z=0