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1.  Innate partnership of HLA-B and KIR3DL1 subtypes against HIV-1 
Nature genetics  2007;39(6):733-740.
Allotypes of the natural killer (NK) cell receptor KIR3DL1 vary in both NK cell expression patterns and inhibitory capacity upon binding to their ligands, HLA-B Bw4 molecules, present on target cells. Using a sample size of over 1,500 human immunodeficiency virus (HIV)+ individuals, we show that various distinct allelic combinations of the KIR3DL1 and HLA-B loci significantly and strongly influence both AIDS progression and plasma HIV RNA abundance in a consistent manner. These genetic data correlate very well with previously defined functional differences that distinguish KIR3DL1 allotypes. The various epistatic effects observed here for common, distinct KIR3DL1 and HLA-B Bw4 combinations are unprecedented with regard to any pair of genetic loci in human disease, and indicate that NK cells may have a critical role in the natural history of HIV infection.
PMCID: PMC4135476  PMID: 17496894
2.  Morbidity Among HIV-1–Infected Mothers in Kenya 
Much of the burden of morbidity affecting women of childbearing age in sub-Saharan Africa occurs in the context of HIV-1 infection. Understanding patterns of illness and determinants of disease in HIV-1–infected mothers may guide effective interventions to improve maternal health in this setting.
We describe the incidence and cofactors of comorbidities affecting peripartum and postpartum HIV-1–infected women in Kenya. Women were evaluated by clinical examination and standardized questionnaires during pregnancy and for up to 2 years after delivery.
Five hundred thirty-five women were enrolled in the cohort (median CD4 count of 433 cells/mm3) and accrued 7736 person-months of follow-up. During 1-year follow-up, the incidence of upper respiratory tract infections was 161 per 100 person-years, incidence of pneumonia was 33 per 100 person-years, incidence of tuberculosis (TB) was 11 per 100 person-years, and incidence of diarrhea was 63 per 100 person-years. Immunosuppression and HIV-1 RNA levels were predictive for pneumonia, oral thrush, and TB but not for diarrhea; CD4 counts <200 cells/mm3 were associated with pneumonia (relative risk [RR] = 2.87, 95% confidence interval [CI]: 1.71 to 4.83), TB (RR = 7.14, 95% CI: 2.93 to 17.40) and thrush. The risk of diarrhea was significantly associated with crowding (RR = 1.86, 95% CI: 1.19 to 2.92) and breast-feeding (RR = 1.71, 95% CI: 1.19 to 2.44). Less than 10% of women reported hospitalization during 2-year follow-up; mortality risk in the cohort was 1.9% and 4.8% for 1 and 2 years, respectively.
Mothers with HIV-1, although generally healthy, have substantial morbidity as a result of common infections, some of which are predicted by immune status or by socioeconomic factors. Enhanced attention to maternal health is increasingly important as HIV-1–infected mothers transition from programs targeting the prevention of mother-to-child transmission to HIV care clinics.
PMCID: PMC3372412  PMID: 17667334
HIV/AIDS; HIV-1 progression; maternal health; morbidity; postpartum; pregnancy; prevention of mother-to-child transmission; women
3.  Static magnets for reducing pain: systematic review and meta-analysis of randomized trials 
Static magnets are marketed with claims of effectiveness for reducing pain, although evidence of scientific principles or biological mechanisms to support such claims is limited. We performed a systematic review and meta-analysis to assess the clinical evidence from randomized trials of static magnets for treating pain.
Systematic literature searches were conducted from inception to March 2007 for the following data sources: MEDLINE, EMBASE, AMED (Allied and Complementary Medicine Database), CINAHL, Scopus, the Cochrane Library and the UK National Research Register. All randomized clinical trials of static magnets for treating pain from any cause were considered. Trials were included only if they involved a placebo control or a weak magnet as the control, with pain as an outcome measure. The mean change in pain, as measured on a 100-mm visual analogue scale, was defined as the primary outcome and was used to assess the difference between static magnets and placebo.
Twenty-nine potentially relevant trials were identified. Nine randomized placebo-controlled trials assessing pain with a visual analogue scale were included in the main meta-analysis; analysis of these trials suggested no significant difference in pain reduction (weighted mean difference [on a 100-mm visual analogue scale] 2.1 mm, 95% confidence interval –1.8 to 5.9 mm, p = 0.29). This result was corroborated by sensitivity analyses excluding trials of acute effects and conditions other than musculoskeletal conditions. Analysis of trials that assessed pain with different scales suggested significant heterogeneity among the trials, which means that pooling these data is unreliable.
The evidence does not support the use of static magnets for pain relief, and therefore magnets cannot be recommended as an effective treatment. For osteoarthritis, the evidence is insufficient to exclude a clinically important benefit, which creates an opportunity for further investigation.
PMCID: PMC1976658  PMID: 17893349
4.  Lytic and Latent Antigens of the Human Gammaherpesviruses Kaposi's Sarcoma-Associated Herpesvirus and Epstein-Barr Virus Induce T-Cell Responses with Similar Functional Properties and Memory Phenotypes▿  
Journal of Virology  2007;81(9):4904-4908.
The cellular immunity against Kaposi's sarcoma-associated herpesvirus (KSHV) is poorly characterized and has not been compared to T-cell responses against other human herpesviruses. Here, novel and dominant targets of KSHV-specific cellular immunity are identified and compared to T cells specific for lytic and latent antigens in a second human gammaherpesvirus, Epstein-Barr virus. The data identify a novel HLA-B57- and HLA-B58-restricted epitope in the Orf57 protein and show consistently close parallels in immune phenotypes and functional response patterns between cells targeting lytic or latent KSHV- and EBV-encoded antigens, suggesting common mechanisms in the induction of these responses.
PMCID: PMC1900166  PMID: 17329344

Results 1-4 (4)