Expression of classical components of the renin-angiotensin system in the human eye.

PURPOSE: The purpose of this study was to determine the relative expression of clinically-relevant components of the renin-angiotensin system (RAS) in the adult human eye. METHODS: We obtained 14 post-mortem enucleated human eyes from patients whom had no history of inflammatory ocular disease nor pre-mortem ocular infection. We determined the gene expression for prorenin, renin, prorenin receptor, angiotensin-converting enzyme, angiotensinogen and angiotensin II Type 1 receptor, on tissue sections and in cultured human primary retinal pigment epithelial and iris pigment epithelial (RPE/IPE) cell lines, using both qualitative and quantitative reverse transcription polymerase chain reaction (RT-PCR). Protein expression was studied using indirect immunofluorescence (IF). RESULTS: Almost all components of the classical RAS were found at high levels, at both the transcript and protein level, in the eyes' uvea and retina; and at lower levels in the cornea, conjunctiva and sclera. There was a much lower level of expression in the reference cultured RPE/IPE cells lines. CONCLUSION: This study describes the distribution of RAS in the normal adult human eye and demonstrates the existence of an independent ocular RAS, with uveal and retinal tissues showing the highest expression of RAS components. These preliminary findings provide scope for examination of additional components of this system in the human eye, as well as possible differential expression under pathological conditions.

A case-control study of the role of human papillomavirus in oesophageal squamous cell carcinoma in australia.

Objective. We investigate the prevalence of human papillomavirus (HPV) in oesophageal squamous cell carcinoma (OSCC) tissues compared to oesophageal tissue from healthy controls, in an Australian cohort. Methods. We conducted a hospital-based case-control study of 99 patients with OSCC and 100 healthy controls to examine the presence of HPV DNA. Paraffin tissues were tested using the PapType high-risk HPV detection and genotyping kit and with INNO-LiPA HPV Genotyping Extra. The biopsy samples were tested for HPV using a PCR-ELISA method based on the L1 consensus primer set PGMY09-PGMY11. Results. HPV DNA of the oncogenic genotype 16 was detected in 1/99 case specimens, a rate of 1010 per 100,000 (95% CI: 30-5500). All control specimens were negative for HPV. Significantly higher rates of smoking, other aerodigestive cancers, and mortality were seen among cases than controls. A pooled analysis of this study and the only other Australian case-control study found that 9/321 cases and 0/155 controls were positive for HPV. The pooled odds ratio for HPV being a risk factor for OSCC was 9.35 (95% CI: 0.47-190.33). Conclusion. Our results suggest that in this multifactorial cancer HPV may be an additional risk factor; although a larger, better powered study is needed.

Evidence for the aetiology of human papillomavirus in oesophageal squamous cell carcinoma in the Chinese population: a meta-analysis.

OBJECTIVES: We aimed to conduct a meta-analysis of human papillomavirus (HPV) as a risk factor for oesophageal squamous cell carcinoma (OSCC) in China, using all eligible studies published in the English and Chinese language literature. DESIGN: The random effect model was used to analyse the pooled OR. The I(2) and Q tests were included in the subgroup analyses. SETTING: Literature searches of databases including MEDLINE, PUBMED, EMBASE and Chinese National Knowledge Infrastructure (CNKI) and other available resources were performed to retrieve studies investigating OSCC tissue from Chinese participants for the presence of HPV DNA. PRIMARY OUTCOME MEASURE: A collective analysis of OSCC cases and control specimens was carried out from 15 case-control studies (6 in the English language and 9 in the Chinese language) for HPV prevalence. RESULTS: Of a total of 1177 OSCC and 1648 oesophageal control samples, 55% (642/1177) of cancer specimens and 27% (445/1648) of control samples were positive for HPV DNA. A positive strong association between HPV DNA and OSCC was observed among the included studies, with a pooled OR of 3.69 (95% CI 2.74 to 4.96). Heterogeneity and publication bias were not observed in the analysis. Subgroup analyses of the included studies also supported the measure of association of causal links between HPV and OSCC. CONCLUSIONS: This meta-analysis provides the strongest evidence until now of an association between HPV and OSCC in the Chinese population. China has a high burden of OSCC, making this an important research finding. A strength and new contribution of this study is combining data from the English and Chinese language literature to analyse all studies conducted in China. These findings may inform the population level use of prophylactic HPV vaccination to reduce the burden of OSCC in China.

The aetiological role of human papillomavirus in oesophageal squamous cell carcinoma: a meta-analysis.

BACKGROUND: The aetiological role of human papillomavirus (HPV) in oesophageal squamous cell carcinoma (OSCC) has been widely researched for more than three decades, with conflicting findings. In the absence of a large, adequately powered single case-control study, a meta-analysis of all available case-control studies is the most rigorous way of identifying any potential association between HPV and OSCC. We present the first global meta-analysis of case-control studies investigating the role of HPV in OSCC. METHODS: Case-control studies investigating OSCC tissue for presence of HPV DNA were identified. 21 case-control studies analyzing a total of 1223 cases and 1415 controls, met our inclusion criteria. HPV detection rates were tabulated for each study and all studies were assessed for quality. The random effects method was used to pool the odds ratios (OR). RESULTS: From all OSCC specimens included in this meta-analysis, 35% (426/1223) were positive for HPV DNA. The pooled OR for an HPV-OSCC association was 3.04 (95% CI 2.20 to 4.20). Meta-regression analysis did not find a significant association between OR and any of the quality domains. Influence analysis was non-significant for the effect of individual studies on the pooled estimate. Studies conducted in countries with low to medium OSCC incidence showed a stronger relationship (OR 4.65, 95% CI 2.47 to 8.76) than regions of high OSCC incidence (OR 2.65, 95% CI 1.80 to 3.91). CONCLUSIONS: Uncertainty around the aetiological role of HPV in OSCC is due largely to the small number and scale of appropriately designed studies. Our meta-analysis of these studies suggests that HPV increases the risk of OSCC three-fold. This study provides the strongest evidence to date of an HPV-OSCC association. The importance of these findings is that prophylactic vaccination could be of public health benefit in prevention of OSCC in countries with high OSCC incidence.

Risk Factors for influenza A(H1N1)pdm09 among students, Beijing, China.

To identify risk factors associated with influenza A(H1N1)pdm09 among students in Beijing, China, we conducted a case-control study. Participants (304 case-patients and 608 controls, age range 6-19 years) were interviewed by using a standardized questionnaire. We found that in addition to vaccination, nonpharmaceutical interventions appeared to be protective.

Role of human papillomaviruses in esophageal squamous cell carcinoma.

Esophageal cancer (EC) is responsible for almost half a million deaths worldwide annually and has a multifactorial etiology, which may account for its geographical variation in incidence. In the last 30 years the potential of human papillomaviruses (HPV) as oncogenes or co-factors in the tumorigenic process of esophageal squamous cell carcinoma (ESCC) has been widely studied. While the etiology of HPV in cervical and certain other anogenital and aerodigestive cancers has been established, results regarding its role in EC have been largely inconclusive. A causal association can be evaluated only with a case-control study, where normal controls are compared to ESCC cases for the presence of HPV. We reviewed all studies investigating ESCC tissue for HPV DNA and identified 139 that met our inclusion criteria, of which only 22 were case-control studies. Our results support previous findings of higher levels of HPV detection in high-risk ESCC regions than in areas of low risk. In addition, we confirm that the role of HPV in ESCC remains unclear, despite an accumulation of studies on the subject. The variations in investigative technique, study design and sample types tested may account for the lack of consistency in results. There is a need for a meta-analysis of all case-control studies to date, and for large, well-designed case-control studies with adequate power to investigate the association. The potential benefits of prophylactic HPV vaccines could be evaluated if HPV is identified as an etiological factor in EC, highlighting the need for further research in this area.

Cholecystokinin octapeptide significantly suppresses collagen-induced arthritis in mice by inhibiting Th17 polarization primed by dendritic cells.

Cholecystokinin octapeptide (CCK-8) is a neuropeptide, and is shown to be a potent immunomodulator with predominant anti-inflammatory effects. Although the regulatory effect of CCK-8 on macrophages and B cells has been defined, the effect of CCK-8 on dendritic cells (DCs) and T cells is not well understood. In this study, we showed that CCK-8 reduced the expression of CD80, CD86, and MHCII on DCs. Moreover, CCK-8 promoted Th1 and inhibited Th17 polarization by increasing the production of IL-12 and decreasing the production of IL-6 and IL-23 on DCs in vitro and in vivo. In addition, intraperitoneal administration of CCK-8 to mice with collagen-induced arthritis (CIA) was found to effectively reduce the incidence of arthritis, delay its onset and prevent the occurrence of joint damage. Collectively, these results suggest that CCK-8 significantly suppresses the incidence and severity of CIA in mice, through the inhibition of DC mediated Th17 polarization.

Do financial factors such as author page charges and industry funding impact on the nature of published research in infectious diseases?

OBJECTIVES: The question of who pays for research to be conducted and published is an important one as it may result in publication bias. The traditional model of medical publishing has relied on subscriptions for funding. There has been increasing interest in making the results of scientific research freely available. One proposed mechanism is an author-pays system, which shifts cost from subscribers to authors. We investigated the impact of author page charges on the nature and type of published research, and the association of industry funding with types of published research. METHODS: Four infectious diseases journals with comparable scope were studied-two with page charges and two without. Variables included type of research study, area of research, author demographics, study setting and industry funding. The differences between a subscription model vs. a mixed model (author page charges and subscription charges) were studied. We also investigated changes within the same journal once it had moved from a subscription model to a mixed model. RESULTS: Authors from developing countries were significantly less likely to be published in the mixed-model journals (OR 0.25, 95% CI 0.15-0.41, P < 0.001). Clinical trials published in any type of journal were significantly more likely to be industry funded than any other type of research (OR 12.7, 95% CI 7.0-22.9, P < 0.001). Industry-funded research was significantly less likely to be about diseases affecting predominantly the developing world (OR 0.47, 95% CI 0.25-0.89, P < 0.05). CONCLUSION: There is clearly a relationship between industry funding and certain types of published research. The model of funding of journal publishing can also affect the nature of published research. Shifting publishing costs to authors favours well-funded organizations, industry sponsored research and wealthy countries. Such potential for publication bias must be considered when planning for open access models.