Pioglitazone administration alters ovarian gene expression in aging obese lethal yellow mice

<p>Abstract</p> <p>Background</p> <p>Women with polycystic ovary syndrome (PCOS) are often treated with insulin-sensitizing agents, e.g. thiazolidinediones (TZD), which have been shown to reduce androgen levels and improved ovulatory function. Acting via peroxisome proliferator-activated receptor (PPAR) gamma, TZD alter the expression of a large variety of genes. Lethal yellow (LY; C57BL/6J Ay/a) mice, possessing a mutation (Ay) in the agouti gene locus, exhibit progressive obesity, reproductive dysfunction, and altered metabolic regulation similar to women with PCOS. The current study was designed to test the hypothesis that prolonged treatment of aging LY mice with the TZD, pioglitazone, alters the ovarian expression of genes that may impact reproduction.</p> <p>Methods</p> <p>Female LY mice received daily oral doses of either 0.01 mg pioglitazone (n = 4) or an equal volume of vehicle (DMSO; n = 4) for 8 weeks. At the end of treatment, ovaries were removed and DNA microarrays were used to analyze differential gene expression.</p> <p>Results</p> <p>Twenty-seven genes showed at least a two-fold difference in ovarian expression with pioglitazone treatment. These included leptin, angiopoietin, angiopoietin-like 4, Foxa3, PGE1 receptor, resistin-like molecule-alpha (RELM), and actin-related protein 6 homolog (ARP6). For most altered genes, pioglitazone changed levels of expression to those seen in untreated C57BL/6J(a/a) non-mutant lean mice.</p> <p>Conclusion</p> <p>TZD administration may influence ovarian function via numerous diverse mechanisms that may or may not be directly related to insulin/IGF signaling.</p

Serum HIV-1 RNA levels and time to development of AIDS in the multicenter hemophilia cohort study

Objective.-To determine if the long-term incidence of the acquired immunodeficiency syndrome (AIDS) is related to human immunodeficiency virus type 1 (HIV-1) RNA levels measured early in HIV-1 infection. Design.-Epidemiologic cohort study. Setting.-Five hemophilia treatment centers in the United States. Subjects.-A total of 165 subjects with hemophilia and HIV-1 infection (age at HIV-1 seroconversion, 1-66 years) followed from 1979 to 1995. Methods.-The HIV-1 RNA level was measured by polymerase chain reaction over a range of 200 to 1 million or more HIV-1 RNA copies/mL. in archived serum specimens collected 12 to 36 months (median, 27 months) after the estimated date of HIV-1 seroconversion. Kaplan-Meier methods were used to examine the risk of AIDS and proportional hazards models were used to estimate relative hazards. Results.-The HIV-1 RNA values were similar in subjects younger than 17 years at seroconversion (median, 5214 copies/mL) and those 18 to 34 years old (median, 4693 copies/mL), but higher in those 35 years or older (median, 12 069 copies/mL) (P=.02 compared with each younger group). At 10 years after seroconversion, the proportions of subjects with AIDS were 72% among subjects with 100 000 or more HIV-1 RNA copies/mL measured 12 to 36 months after HIV-1 seroconversion (n=9), 52% among subjects with 10 000 to 99 999 copies/mL (n=55), 22% among subjects with 1000 to 9999 copies/mL (n=82), and 0% among subjects with fewer than 1000 copies/mL (n=19) (P&lt;.001). The age-adjusted relative hazard for AIDS for subjects with 10 000 or more copies/mL was 14.3 (95% confidence interval, 1.9-105.6) compared with subjects with fewer than 1000 copies/mL. Conclusions.-The HIV-1 RNA level during early chronic HIV-1 infection is a strong, age-independent predictor of clinical outcome; low revels define persons with a high probability of long-term AIDS-free survival

Serum HIV-1 RNA levels and time to development of AIDS in the multicenter hemophilia cohort study

Objective.-To determine if the long-term incidence of the acquired immunodeficiency syndrome (AIDS) is related to human immunodeficiency virus type 1 (HIV-1) RNA levels measured early in HIV-1 infection. Design.-Epidemiologic cohort study. Setting.-Five hemophilia treatment centers in the United States. Subjects.-A total of 165 subjects with hemophilia and HIV-1 infection (age at HIV-1 seroconversion, 1-66 years) followed from 1979 to 1995. Methods.-The HIV-1 RNA level was measured by polymerase chain reaction over a range of 200 to 1 million or more HIV-1 RNA copies/mL. in archived serum specimens collected 12 to 36 months (median, 27 months) after the estimated date of HIV-1 seroconversion. Kaplan-Meier methods were used to examine the risk of AIDS and proportional hazards models were used to estimate relative hazards. Results.-The HIV-1 RNA values were similar in subjects younger than 17 years at seroconversion (median, 5214 copies/mL) and those 18 to 34 years old (median, 4693 copies/mL), but higher in those 35 years or older (median, 12 069 copies/mL) (P=.02 compared with each younger group). At 10 years after seroconversion, the proportions of subjects with AIDS were 72% among subjects with 100 000 or more HIV-1 RNA copies/mL measured 12 to 36 months after HIV-1 seroconversion (n=9), 52% among subjects with 10 000 to 99 999 copies/mL (n=55), 22% among subjects with 1000 to 9999 copies/mL (n=82), and 0% among subjects with fewer than 1000 copies/mL (n=19) (P Conclusions.-The HIV-1 RNA level during early chronic HIV-1 infection is a strong, age-independent predictor of clinical outcome; low revels define persons with a high probability of long-term AIDS-free survival

INCIDENCE OF LYMPHOMAS AND OTHER CANCERS IN HIV-INFECTED AND HIV-UNINFECTED PATIENTS WITH HEMOPHILIA

Objective. - To determine the types and rates of cancers occurring in excess in the presence of infection with the human immunodeficiency virus type 1 (HIV-1). Design. - Cohort analytic study of HIV-infected and HIV-uninfected subjects followed for up to 12 years. Setting. - Fifteen hemophilia treatment centers. Patients. - A total of 1701 patients with hemophilia, of whom 1065 (63%) were HIV-1 seropositive. Main Outcome Measures. -Morphologic classification and incidence rates of cancers. Main Results. - The incidence of non-Hodgkin's lymphoma after HIV seroconversion averaged 0.15 case per 100 person-years (95% confidence interval [Cl], 0.08 to 0.25) and rose exponentially with increasing duration of HIV infection. Although the greatest absolute risk of lymphoma was in the oldest age group, the relative increase compared with general population rates was 38-fold in subjects 10 to 39 years old and 12-fold in older subjects (P Conclusions. - HIV infection has restricted effects on cancer incidence that are only partly explained by immunosuppression. Paradoxically, improvements in therapy of HIV infection that prolong survival may lead to further increases in HIV-associated lymphoma