The effect of valacyclovir treatment on natural killer cells of infertile women.

PROBLEM: The aim of this study was to investigate the effect of valacyclovir treatment on natural killer (NK) cell concentration in the peripheral blood of infertile women. METHOD OF STUDY: Peripheral blood NK cell concentration of 104 non-pregnant women with a history of infertility was determined by flow cytometry. The controls were 14 fertile non-pregnant women. A cohort of 42 out of 104 women--whose NK cell levels were 175/microL or higher--was prospectively studied for the presence of HSV-1, 2, VZV, cytomegalovirus, HHV-6, HHV-7 and HHV-8 DNA in the peripheral blood and was orally administered valacyclovir (open label study). RESULTS: Herpes virus DNA was detected in 64.3% of the 42 women examined. Prior to valacyclovir treatment mean NK cell concentration in herpes-negative group was statistically higher from control group but lower from herpes positive group (P = 0.0007, ANOVA). Following valacyclovir treatment the mean NK cell concentration was statistically decreased in all studied women (P = 0.000453), in herpes-negative (P = 0.01622) and in herpes positive group (P = 0.0056). Sufficient decrease was observed in 31 (73.8%) of 42 women who received the drug. CONCLUSIONS: Valacyclovir treatment is associated with a decrease of NK cell levels in most of the women with a history of infertility.

Functional role of the four different types of (AT)(x)T(y) motifs 5' to the beta-globin gene and their distribution in the Greek population.

The polymorphic sequence (AT)(X)T(Y) motif residing 0.5 kb 5' to the human -globin gene has been shown to be a binding site for a putative repressor protein, BP1, in K562 cells. The (AT)(X)T(Y) sequence is characterized by variable length and several configurations. The precise role of the (AT)(X)T(Y) repeats on the regulation of the -globin gene remains unclear. In the present study, we identified the (AT)(X)T(Y) motifs which prevail in the Greek population, established their frequency, and directly investigated their role on -globin gene expression by comparing the effects of the four identified (AT)(X)T(Y) motifs using transient expression assays. Four different configurations were found in the Greek population: the (AT)7T7 motif was the most abundant (81.8%) representing the reference sequence, the (AT)9T5 motif (16.1%), and the (AT)11T3 motif (2%), while the (AT)8T4 motif was absent from normal A chromosomes and was exclusively found on s chromosomes. To evaluate their different role on transcriptional regulation, the four motifs were subcloned upstream of the luciferase reporter gene. Two expression systems were used; MEL cells were transfected with a pGL-2 basic plasmid containing one of the four (AT)(X)T(Y) repeats, the -globin gene promoter, and the luciferase gene, while HeLa cells were transfected with a similar construct (pGL-2 enhancer) including the SV40 enhancer. After 48 h following transient transfection of the cell lines, the expression level of the reporter gene was estimated using a photoilluminometer. The transfected MEL cells exhibited a clearly reduced expression of the luciferase gene driven by the -globin promoter containing the (AT)9T5 and (AT)11T3 configurations. In contrast, HeLa cells did not exhibit any differences among the four motifs. On the basis of these results, we postulate that the (AT)9T5 and (AT)11T3 variants residing 0.5 kb 5' to the -globin gene do not represent simple polymorphisms and can affect its expression in an erythroid environment.