Evaluation of interleukin-6 and interleukin-10 in lung transplant patients with human cytomegalovirus infection

Abstract:  We hypothesized that interleukin-6 (IL-6) in plasma and bronchoalveolar lavage (BAL) might serve as additional diagnostic parameter in lung transplant patients with human cytomegalovirus (HCMV) infection. Therefore, we compared IL-6 levels in HCMV-positive vs. HCMV-negative patients. IL-6 was measured by ELISA in plasma and BAL in 111 patients. Furthermore, we investigated the influence of IL-10 on IL-6 production in HCMV-positive patients. For HCMV–DNA detection in plasma and BAL a quantitative polymerase chain reaction (PCR) assay was used. IL-6 levels were significantly higher in the HCMV-positive group (n = 39; BAL p = 0.045; plasma p = 0.017) in comparison to the HCMV-negative group (n = 72). IL-10 did not correlate with IL-6 concentration (p = 0.146). Donor (D) or recipient (R) HCMV-constellation did not influence IL-6 concentration. IL-6 levels were not influenced by elevated levels of HCMV copies. Our data suggest that IL-6 does not serve as a good diagnostic parameter for existence of HCMV infection in lung transplant patients. Because of the wide range of the IL-6 levels in both groups, we were not able to find a breakpoint differentiating between infected and not-infected patients. Another important finding was that IL-6 production is not dependent of the HCMV status of D/R.     

Protective role of the apolipoprotein E2 allele in age-related disease traits and survival: evidence from the Long Life Family Study

The apolipoprotein E (apoE) is a classic example of a gene exhibiting pleiotropism. We examine potential pleiotropic associations of the apoE2 allele in three biodemographic cohorts of long-living individuals, offspring, and spouses from the Long Life Family Study, and intermediate mechanisms, which can link this allele with age-related phenotypes. We focused on age-related macular degeneration, bronchitis, asthma, pneumonia, stroke, creatinine, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol, diseases of heart (HD), cancer, and survival. Our analysis detected favorable associations of the ε2 allele with lower LDL-C levels, lower risks of HD, and better survival. The ε2 allele was associated with LDL-C in each gender and biodemographic cohort, including long-living individuals, offspring, and spouses, resulting in highly significant association in the entire sample (β = ?7.1, p = 6.6 × 10^?44). This allele was significantly associated with HD in long-living individuals and offspring (relative risk [RR] = 0.60, p = 3.1 × 10^?6) but this association was not mediated by LDL-C. The protective effect on survival was specific for long-living women but it was not explained by LDL-C and HD in the adjusted model (RR = 0.70, p = 2.1 × 10^?2). These results show that ε2 allele may favorably influence LDL-C, HD, and survival through three mechanisms. Two of them (HD- and survival-related) are pronounced in the long-living parents and their offspring; the survival-related mechanism is also sensitive to gender. The LDL-C-related mechanism appears to be independent of these factors. Insights into mechanisms linking ε2 allele with age-related phenotypes given biodemographic structure of the population studied may benefit translation of genetic discoveries to health care and personalized medicine.     

Evidence that the retroviral DNA integration process triggers an ATR-dependent DNA damage response

Caffeine is an efficient inhibitor of cellular DNA repair, likely through its effects on ATM (ataxia telangiectasia mutated) and ATR (ATM and Rad3-related) kinases. Here, we show that caffeine treatment causes a dose-dependent reduction in the total amount of HIV-1 and avian sarcoma virus retroviral vector DNA that is joined to host DNA in the population of infected cells and also in the number of transduced cells. These changes were observed at caffeine concentrations that had little or no effect on overall cell growth, synthesis, and nuclear import of the viral DNA, or the activities of the viral integrase in vitro. Substantial reductions in the amount of host-viral-joined DNA in the infected population, and in the number of transductants, were also observed in the presence of a dominant-negative form of the ATR protein, ATRkd. After infection, a significant fraction of these cells undergoes cell death. In contrast, retroviral transduction is not impeded in ATM-deficient cells, and addition of caffeine leads to the same reduction that was observed in ATM-proficient cells. These results suggest that activity of the ATR kinase, but not the ATM kinase, is required for successful completion of the viral DNA integration process and/or survival of transduced cells. Components of the cellular DNA damage repair response may represent potential targets for antiretroviral drug development.     

Body mass index and nine-year mortality in disabled and nondisabled older U.S. individuals

OBJECTIVES: To investigate the relationship between body mass index (BMI) and 9-year mortality in older (≥65) Americans with and without disability.
DESIGN: Cohort study.
SETTING: The unique disability-focused National Long Term Care Survey (NLTCS) data that assessed the health and well-being of older individuals in 1994 were analyzed.
PARTICIPANTS: Four thousand seven hundred ninety-one individuals in the 1994 survey.
MEASUREMENTS: BMI (kg/m²) was calculated from self- or proxy reports of height and weight. The analysis was adjusted for 1-year change in BMI and demographic and health-related factors, as well as reports by proxies, and death occurring during the first 2 years after the interview.
RESULTS: The relative risk of death as a function of BMI formed a nonsymmetric U-shaped pattern, with larger risks associated with lower BMI (<22.0) and minimal risks for BMI of 25.0 to 34.9. (BMI 22.0–24.9 was the reference.) Adjustments for demographic and health-related factors had little effect on this pattern. Nondisabled individuals exhibited a similar U-shaped pattern but with lower risks associated with lower BMI. For disabled individuals, the mortality–risk pattern was higher for lower BMI (<22.0) and flat for higher BMI, thus exhibiting an inverse J shape. BMI patterns were age sensitive, with disability status affecting sensitivity.
CONCLUSION: Overweight or mild (grade 1) obesity was not a risk factor for 9-year mortality in older Americans participating in the 1994 NLTCS. A flatter BMI pattern of the relative risk of death for disabled than for nondisabled individuals suggests that optimal body weight can be sensitive to age and health and well-being.     

Digital Leg Volume Quantification: Precision Assessment of a Novel Workflow Based on Single Capture Three-dimensional Whole-Body Surface Imaging

Journal of Digital Imaging - Whole-body three-dimensional surface imaging (3DSI) offers the ability to monitor morphologic changes in multiple areas without the need to individually scan every...