Immunomodulation by imiquimod in patients with high-risk primary melanoma.

Imiquimod is a synthetic Toll-like receptor 7 (TLR7) agonist approved for the topical treatment of actinic keratoses, superficial basal cell carcinoma, and genital warts. Imiquimod leads to an 80-100% cure rate of lentigo maligna; however, studies of invasive melanoma are lacking. We conducted a pilot study to characterize the local, regional, and systemic immune responses induced by imiquimod in patients with high-risk melanoma.

ADH1B*1, ADH1C*2, DRD2 (-141C Ins), and 5-HTTLPR are associated with alcoholism in Mexican American men living in Los Angeles.

Background: The aim of the present study was to use a candidate gene approach to identify the genetic risk factors for alcoholism in Mexican Americans residing in the Los Angeles area. The genes selected include alcohol metabolizing genes and neurotransmitter genes, which have been shown in the literature to be associated with alcoholism in other ethnic groups.

Methods: Thirteen allelic variants from seven genes were evaluated for their role in alcoholism using alcoholic (n = 200) and nonalcoholic (n = 251) Mexican Americans.

Polymorphisms of the dopamine D2 receptor, serotonin transporter, and GABA(A) receptor beta(3) subunit genes and alcoholism in Mexican-Americans.

The etiology of alcohol dependence is a complex interaction of psychosocial and biologic factors. To study the impact of genetic factors that play an important role in an individual's vulnerability to alcohol abuse and dependence, we examined the genetic variations of the major neurotransmitter genes, including the dopamine D2 receptor (DRD2) TaqI A, B, and -141C insertion/deletion (Ins/Del) polymorphisms, the serotonin transporter-linked polymorphic region (5-HTTLPR), and the gamma-aminobutyric acid A (GABA(A)) receptor beta(3) subunit gene (GABRbeta3), for 130 Mexican-American alcoholic men and 251 nonalcoholic control subjects (105 men and 146 women). The genotype frequency for the DRD2 -141C Ins/Del allele was significantly different between alcoholic and control subjects (P=.

Cytochrome P450 genes are differentially expressed in female and male hepatocyte retinoid X receptor alpha-deficient mice.

To study the functional role of retinoid X receptor alpha (RXRalpha) in hepatocytes, hepatocyte RXRalpha-deficient mice have been established. Characterization has been performed on male mice. In this paper, we show that the expression of CYP450 genes is differentially expressed in male and female hepatocyte RXRalpha-deficient mice; male mice have reduced expression of cytochrome P450 (CYP) CYP4A, CYP3A, and CYP2B mRNAs, but females do not exhibit such phenotypes.

The ADH3*2 and CYP2E1 c2 alleles increase the risk of alcoholism in Mexican American men.

To identify the association between the polymorphisms of genes encoding alcohol metabolizing enzymes and alcoholism, the alcohol dehydrogenase 2 (ADH2), alcohol dehydrogenase 3 (ADH3), aldehyde dehydrogenase 2 (ALDH2), and cytochrome P450 2E1 (CYP2E1) genes were studied in 101 male Mexican American alcoholics. One hundred and four Mexican American nonalcoholic males served as controls. The allele frequency of ADH2*2 (4.

Hepatocyte retinoid X receptor-alpha-deficient mice have reduced food intake, increased body weight, and improved glucose tolerance.

Hepatocyte retinoid X receptor (RXR)alpha-deficient mice and wild-type mice were fed either a regular or a high-saturated-fat diet for 12 wk to study the functional role of hepatocyte RXRalpha in fatty acid and carbohydrate metabolism. Food intake was significantly reduced in hepatocyte RXRalpha-deficient mice when either diet was used. The amount of food intake was negatively associated with serum leptin level.

The role of hepatocyte RXR alpha in xenobiotic-sensing nuclear receptor-mediated pathways.

Nuclear receptors constitutive androstane receptor (CAR) and pregnane X receptor (PXR) cross talk and serve as xenobiotic sensors to form a safety net against the toxic effects of harmful substances. Retinoid x receptor alpha (RXRalpha) dimerizes with CAR and PXR. In order to analyze the role of RXRalpha in these xeno-sensor-mediated pathways, hepatocyte RXRalpha-deficient mice were challenged by CAR and PXR ligands including androstanol, 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP), and pregnenolone 16alpha-carbonitrile (PCN).