The hepatic uptake of bile acids from the portal circulation is primarily dependent upon a sodium-dependent basolateral membrane transporter. In order to begin to investigate the factors controlling rat liver sodiumdependent bile acid cotransporter (ntcp) gene expression, we isolated Ϸ30 kilobase pairs of rat genomic DNA in three overlapping phage clones. The rat ntcp gene is distributed over 16.5 kilobase pairs as five exons. Primer extension analysis revealed two closely spaced transcription initiation sites, 27 and 41 nucleotides downstream of a TATA sequence. Regulation of transcription was investigated first by transfection of primary rat hepatocytes by a series of 5-deleted rat ntcp promoterdriven luciferase constructs (from Ϸ ؊6 kilobase pairs to ؊59 base pairs of upstream sequences, terminating at nucleotide ؉47), identifying a minimal promoter element: nucleotide ؊158 to ؉47. This minimal promoter was active in transfected HepG2, but inactive in NIH3T3, Caco-2, and Madin-Darby canine kidney cells, indicating that the determinants of hepatocyte-specific expression reside within this region. The individual elements within the minimal promoter were investigated via transfection of HepG2 cells by a series of 20 mutant plasmids, each containing a 10-base pair sequential block mutation. Eight mutant constructs profoundly suppressed promoter activity; encompassing sequences from ؊66 to ؉4 nt, and ؉15 to ؉24 nucleotides, while no other 10-base pair mutation significantly interfered with minimal promoter activity. Deoxyribonuclease I footprint analysis of the minimal promoter revealed three bound regions; ؊92 to ؊74 (footprint C), ؊50 to ؊37 (footprint B), and ؊17 to ؉12 (footprint A). Gel mobility shift assays provided evidence for hepatocyte nuclear factor 1 binding within footprint A and a liverenriched factor(s) that binds within a novel palindrome in footprint B. These studies indicate that three elements direct the basal and tissue-restricted expression of the rat ntcp promoter; a TATA element, the liverenriched transcription factor hepatocyte nuclear factor 1, and an unknown liver-enriched factor that binds within a novel palindrome in footprint B.

OBJECTIVE To evaluate the relationship between change in weight and pelvic organ prolapse (POP) progression/regression in women during a 5-year period. METHODS Postmenopausal women with uteri (N=16,608), ages 50 to 79, who were enrolled in the Women's Health Initiative (WHI) Estrogen plus Progestin Clinical Trial between 1993 and 1998 were included in this secondary analysis. Baseline pelvic examination, repeated annually, assessed uterine prolapse, cystocele, and rectocele using the WHI Prolapse Classification System. Statistical analyses included univariate and multiple logistic regression methods. RESULTS During the 5-year time period, the majority of women (9,251, 55.7%) gained weight (mean 4.43 kg, ± 5.95 kg), and the overall rate of prolapse (WHI Prolapse Classification System: grades 1-3) increased from 40.9% at baseline to 43.8% at year 5 of evaluation. Controlling for age, parity, race, and other health/physical variables, being overweight (body mass index [BMI] between 25 and 29.9) or obese (BMI of at least 30) at baseline was associated with progression in cystocele, rectocele, and uterine prolapse compared with women with healthy BMIs (BMI is calculated as weight (kg)/[height (m)]2). Specifically, the risk of prolapse progression in overweight and obese women as compared with the participants with healthy BMIs increased by 32% and 48% for cystocele, by 37% and 58% for rectocele, and by 43% and 69% for uterine prolapse, respectively. Adjusting for women with prolapse at baseline and baseline BMI, a 10% weight change was associated with minimal change in overall POP. Specifically, a 10% weight loss was associated with a borderline worsening of uterine prolapse (odds ratio [OR] 0.93, 95% confidence interval [CI] 0.88-0.97) and a minimal regression of cystocele (OR 1.03, 95% CI 1.00-1.05) and rectocele (OR 1.04, 95% CI 1.01-1.07). CONCLUSION Being overweight or obese is associated with progression of POP. Weight loss does not appear to be significantly associated with regression of POP, suggesting that damage to the pelvic floor related to weight gain might be irreversible.

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Reduction of severe perineal trauma by restricted use of the 2 modifiable clinical variables, episiotomy and forceps, is evident over time.

Six sequences that are closely related to the S gene family of the largely self-incompatible Brassica species have been identified in self-fertilizing Arabidopsis. The sequences define four genomic regions that map to chromosomes 1 and 3. Of the four functional genes identified, only the previously reported Arabidopsis AtS1 gene was expressed specifically in papillar cells and may function in pollination. The remaining three genes, including two novel genes designated ARK2 and ARK3, encode putative receptor-like serine/threonine protein kinases that are expressed predominantly in vegetative tissues. ARK2 promoter activity was detected exclusively in above-ground tissues, specifically in cotyledons, leaves, and sepals, in correlation with the maturation of these structures. ARK3 promoter activity was detected in roots as well as above-ground tissues but was limited to small groups of cells in the root-hypocotyl transition zone and at the base of lateral roots, axillary buds, and pedicels. The nonoverlapping patterns of expression of the ARK genes and the divergence of their sequences, particularly in their predicted extracellular domains, suggest that these genes perform nonredundant functions in specific aspects of development or growth of the plant body.