Associations of plasma miRNAs with waist circumference and insulin resistance among women with polycystic ovary syndrome - Pilot study.

Background: Insulin resistance (IR) and central obesity are common in polycystic ovary syndrome (PCOS), but pathomechanisms for IR in PCOS are not established. Circulating microRNAs (miRNAs) are non-invasive biomarkers of epigenetic regulation that may contribute to the pathogenesis of IR and central adiposity in PCOS.

Methods: We conducted a pilot study to examine associations of circulating miRNAs with IR and central adiposity among women with PCOS (n = 11) using high-throughput miRNA sequencing.

Persistence of improved glucose homeostasis in Gclm null mice with age and cadmium treatment.

Antioxidant signaling/communication is among the most important cellular defense and survival pathways, and the importance of redox signaling and homeostasis in aging has been well-documented. Intracellular levels of glutathione (GSH), a very important endogenous antioxidant, both govern and are governed by the Nrf2 pathway through expression of genes involved in its biosynthesis, including the subunits of the rate-limiting enzyme (glutamate cysteine ligase, GCL) in GSH production, GCLC and GCLM. Mice homozygous null for the Gclm gene are severely deficient in GSH compared to wild-type controls, expressing approximately 10% of normal GSH levels.

Short Report: Circulating microRNAs are associated with incident diabetes over 10 years in Japanese Americans.

Epigenetic changes precede the development of diabetes by many years, providing clues to its pathogenesis. We explored whether the epigenetic markers, circulating microRNAs (miRNAs), were associated with incident diabetes in Japanese Americans. We conducted a pilot study (n = 10) using plasma from age- and sex-matched participants who did or did not develop diabetes in the Japanese American Community Diabetes Study, an observational study of diabetes risk factors.

Group B Streptococcus circumvents neutrophils and neutrophil extracellular traps during amniotic cavity invasion and preterm labor.

Preterm birth is a leading cause of neonatal morbidity and mortality. Although microbial invasion of the amniotic cavity (MIAC) is associated with the majority of early preterm births, the temporal events that occur during MIAC and preterm labor are not known. Group B Streptococci (GBS) are β-hemolytic, gram-positive bacteria, which commonly colonize the vagina but have been recovered from the amniotic fluid in preterm birth cases.

Association of diabetes susceptibility gene calpain-10 with pancreatic cancer among smokers.

Objective: The objective of this study was to test the association between calpain-10 (CAPN10), a diabetes susceptibility gene, with risk of pancreatic cancer (PC).

Methods: DNA samples from 83 incident exocrine PC cases and 166 controls, all of whom were smokers, were genotyped for four markers of CAPN10 in a nested case-control study based on the Beta-Carotene and Retinol Efficacy Trial (CARET), a randomized chemoprevention trial of subjects at high risk of lung cancer. Controls were matched on sex, race, age, CARET intervention arm, duration of exposure to asbestos, and smoking history.

Association between the peroxisome proliferator-activated receptor gamma Pro12Ala variant and haplotype and pancreatic cancer in a high-risk cohort of smokers: a pilot study.

Objectives: The Pro12Ala variant in the peroxisome proliferator-activated receptor gamma (PPARG) gene has been associated with diabetes and several cancers. This pilot study tested for the association between Pro12Ala and pancreatic cancer risk in a high-risk sample of smokers.

Methods: A nested case-control study was conducted in 83 incident cases of pancreatic cancer and 166 matched controls originally recruited into a cohort chemoprevention study of lung cancer.

A case study of acenocoumarol sensitivity and genotype-phenotype discordancy explained by combinations of polymorphisms in VKORC1 and CYP2C9.

To determine the cause of a genotype-phenotype discordancy for acenocoumarol sensitivity. Methods A patient, highly sensitive to acenocoumarol, and previously determined to carry only a single CYP2C9*3 allele, was genotyped for additional functionally defective alleles in the CYP2C9 and VKORC1 genes. Family members were also analyzed to trace the pedigree.

Acetaminophen-induced liver injury is attenuated in male glutamate-cysteine ligase transgenic mice.

Acetaminophen overdose is a leading cause of drug-related acute liver failure in the United States. Glutathione, a tripeptide antioxidant protects cells against oxidative damage from reactive oxygen species and plays a crucial role in the detoxification of xenobiotics, including acetaminophen. Glutathione is synthesized in a two-step enzymatic reaction.

Genetic Susceptibility to Prostate Cancer: Prostate-specific Antigen and its Interaction with the Androgen Receptor (United States).

Objective: To determine whether directly observed prostate-specific antigen (PSA) promoter diploid haplotype, either alone or in conjunction with androgen receptor (AR) genotype, is associated with prostate cancer risk.

Methods: We conducted a case-control study nested within the US population-based Cardiovascular Health Study cohort. Incident prostate cancers were identified by linkage to cancer registry records for the years 1989-2000.

Gene expression profiling of nephrotoxicity from the sevoflurane degradation product fluoromethyl-2,2-difluoro-1-(trifluoromethyl)vinyl ether ("compound A") in rats.

The major degradation product of the volatile anesthetic sevoflurane, the haloalkene fluoromethyl-2,2-difluoro-1-(trifluoromethyl)vinyl ether (FDVE or "compound A"), is nephrotoxic in rats. FDVE undergoes complex metabolism and bioactivation, which mediates the nephrotoxicity. Nevertheless, the molecular and cellular mechanisms of FDVE toxification are unknown.

The Prevalence of CYP2C8, 2C9, 2J2, and soluble epoxide hydrolase polymorphisms in African Americans with hypertension.

Background: The cytochrome P450 (CYP) epoxygenase pathway produces arachidonic acid metabolites that are vasoactive, that affect renal sodium handling, and that have been proposed to play a mechanistic role in hypertension. Multiple single nucleotide polymorphisms (SNP) in CYP2C8, 2C9, 2J2 and soluble epoxide hydrolase (sEH) have been identified, many of which have altered functional activity in vitro. We performed a case-control study to determine the prevalence of epoxygenase-related SNP in African American individuals and to evaluate whether these SNP are associated with increased risk of hypertension.

Association between CYP2C9 genetic variants and anticoagulation-related outcomes during warfarin therapy.

Context: Warfarin is a commonly used anticoagulant that requires careful clinical management to balance the risks of overanticoagulation and bleeding with those of underanticoagulation and clotting. The principal enzyme involved in warfarin metabolism is CYP2C9, and 2 relatively common variant forms with reduced activity have been identified, CYP2C9*2 and CYP2C9*3. Patients with these genetic variants have been shown to require lower maintenance doses of warfarin, but a direct association between CYP2C9 genotype and anticoagulation status or bleeding risk has not been established.