Investigating biogeographic boundaries of the Sunda shelf: A phylogenetic analysis of two island populations of Macaca fascicularis.

OBJECTIVES: Cyclical submergence and re-emergence of the Sunda Shelf throughout the Pleistocene served as a dynamic biogeographic landscape, across which long-tailed macaques (Macaca fascicularis) have migrated and evolved. Here, we tested the integrity of the previously reported continental-insular haplotype divide reported among Y and mitochondrial DNA lineages across multiple studies. MATERIALS AND METHODS: The continental-insular haplotype divide was tested by heavily sampling wild macaques from two important biogeographic regions within Sundaland: (1) Singapore, the southernmost tip of continental Asia and (2) Bali, Indonesia, the southeastern edge of the Indonesian archipelago, immediately west of Wallace's line. Y DNA was haplotyped for samples from Bali, deep within the Indonesian archipelago. Mitochondrial D-loop from both islands was analyzed against existing data using Maximum Likelihood and Bayesian approaches. RESULTS: We uncovered both "continental" and "insular" Y DNA haplotypes in Bali. Between Singapore and Bali we found 52 unique mitochondrial haplotypes, none of which had been previously described. Phylogenetic analyses confirmed a major haplogroup division within Singapore and identified five new Singapore subclades and two primary subclades in Bali. DISCUSSION: While we confirmed the continental-insular divide among mtDNA haplotypes, maintenance of both Y DNA haplotypes on Bali, deep within the Indonesian archipelago calls into question the mechanism by which Y DNA diversity has been maintained. It also suggests the continental-insular designation is less appropriate for Y DNA, leading us to propose geographically neutral Y haplotype designations.

Negative perceptions about condom use in a clinic population: comparisons by gender, race and age.

We sought to elucidate the associations of 13 items assessing negative perceptions about condom use with gender, age and race in a sample of clinic attendees. Patients from four clinics, in three US cities, were recruited (N = 928). Data were collected using audio-computer-assisted self-interviewing. The primary measure was a 13-item adapted version of the Condom Barriers Scale. Logistic regression and chi-square tests were employed to relate the 13 items to gender, age and race. Gender, race and age all had significant associations with negative perceptions of condoms and their use. A primary finding was a large number of significant differences between men and women, with negative perceptions more common among women than among men. For African Americans, especially women, negative perceptions were more common among older participants than among younger participants. In conclusion, important demographic differences regarding negative perceptions may inform the tailoring of intervention efforts that seek to rectify negative perceptions about condoms and thus promote condom use among individuals at risk for sexually transmitted infections (STIs) in the USA. On the other hand, our findings also suggest that the majority of STI clinic attendees may hold positive perceptions about condoms and their use; maintaining and building upon these positive perceptions via education, counselling, and access is also important.

A comparison of condom use errors and problems for heterosexual anal and vaginal intercourse.

Condom use errors and problems were compared for anal and vaginal intercourse among a convenience sample of heterosexual men aged 18-66 years (n = 757). Men completed an online questionnaire for the last male condom use event for penile-anal (10.4%) or penile-vaginal (89.6%) intercourse. The prevalence of condom use errors and problems was similar regardless of intercourse type with a few exceptions; those reporting anal intercourse were significantly more likely to report using water-based (P < 0.001) and oil-based (P = 0.037) lubricant and to remove condoms before sex was finished (P < 0.001). The large majority of the sample (93.8%) reported at least one of the nine errors assessed and almost half (46.2%) reported at least one of the seven problems, indicating that many adults may need assistance with these issues. Condom use promotion programmes designed for heterosexual adults are needed that address condom use errors and problems for penile-anal as well as penile-vaginal intercourse.

The semantics of sexual behavior and their implications for HIV/AIDS research and sexual health: US and UK gay men's definitions of having "had sex".

Understanding the definition and meaning of the word "sex" has implications for sexual medicine, HIV/AIDS research, and clinical practices. Previous studies have reported variations in the definition of having "had sex" and the necessity of using behaviorally specific terminology when taking sexual histories and assessing sexual risk. The purpose of the current study is to assess gay men's definitions of what constitutes having "had sex." Two international convenience samples are compared: a UK sample of 180 self-identified gay men ranging from 18 to 56 years of age (M=36 years; SD=8.29) and a US sample of 190 self-identified gay men ranging 18-74 years of age (M=33.9 years; SD=12.49). Both groups were asked to indicate whether each of a list of sexual behaviors was considered having "had sex." Almost all participants (~95%) believed that penile-anal intercourse constituted having "had sex." US and UK gay men differed in defining the following as having "had sex": giving oral-genital stimulation (US 71.6%, UK 84.9%, P=0.002); giving (G) and receiving (R) manual-anal stimulation (G: US 53.4%, UK 70.9%, P=0.001; R: US 53.7%, UK 71.2%, P=0.001); giving and receiving oral-anal stimulation (G: US 61.2%, UK 78.4%, P<0.001; R: US 59.3%, UK 78.1, P<0.001); and giving and receiving sex-toy stimulation (G: US 55%, UK 77.1%, P<0.001; R: US 56.1%, UK 77.7%, P<0.001). It is important to note that regardless of country there was not overall consensus on which behaviors constituted having "had sex." These findings reinforce the need for behavioral specificity in documenting sexual histories and assessing sexual risk. Further, researchers and clinicians should exercise caution by not assuming that their own definitions of the term "sex" is shared by their gay male participants or patients.

Does it fit okay? Problems with condom use as a function of self-reported poor fit.

OBJECTIVE: To identify associations between men's self-reports of ill-fitting condoms and selected condom use problems, using an event-specific analysis. METHODS: A convenience sample of men was recruited via advertisements in newspapers (two urban and one small town) and a blog on the website of a condom sales company. Men completed a questionnaire posted on the website of The Kinsey Institute for Research in Sex, Gender, and Reproduction. Inclusion criteria were: at least 18 years old, used condoms for penile-vaginal intercourse in the past 3 months and the ability to read English. RESULTS: In controlled, event-specific, analyses of 436 men, those reporting ill-fitting condoms (44.7%) were significantly more likely to report breakage (adjusted odds ratio (AOR 2.6), slippage (AOR 2.7), difficulty reaching orgasm, both for their female partners (AOR 1.9) and for themselves (AOR 2.3). In addition, they were more likely to report irritation of the penis (AOR 5.0) and reduced sexual pleasure, both for their female partner (AOR 1.6) and for themselves (AOR 2.4). Furthermore, they were more likely to report that condoms interfered with erection (AOR 2.0), caused erection loss (AOR 2.3), or became dry during sex (AOR 1.9). Finally, they were more likely to report removing condoms before penile-vaginal sex ended (AOR 2.0). CONCLUSIONS: Men and their female sex partners may benefit from public health efforts designed to promote the improved fit of condoms.

Is phosphodiesterase type 5 inhibitor use associated with condom breakage?

We tested the hypothesis that phosphodiesterase type 5 inhibitor (PDE5i) use would be associated with increased likelihood of condom breakage using an event-specific analysis. A convenience sample of 440 men completed an internet-based questionnaire that assessed variables pertaining to the last time they used condoms for penile-vaginal intercourse (PVI). A bivariate (screening) analysis was performed to identify covariates for a multivariate analysis using logistic regression. Altogether, 5.9% of the men reported breakage and 9.5% reported PDE5i use during the last time a condom was used for PVI. Among men who had used PDE5i during the last condom-protected occasion of PVI, 11.9% reported breakage compared with 5.3% of those not reporting PDE5i use. Adjusting for men's age, ethnic minority status, marital status, reported duration of PVI and alcohol use at last PVI, those using PDE5i were about four times more likely to also report condom breakage (AOR 4.02; 95% CI 1.20 to 13.48; p = 0.04). Of note, duration of PVI was independently associated with breakage (AOR 1.36; CI 1.02 to 1.83; p = 0.04). Findings suggest that PDE5i use may potentially be associated with increased odds of condom breakage among some men.

Two heads are better than one: the association between condom decision-making and condom use errors and problems.

OBJECTIVES: This exploratory study compared the frequency of condom use errors and problems between men reporting that condom use for penile-vaginal sex was a mutual decision compared with men making the decision unilaterally. METHODS: Nearly 2000 people completed a web-based questionnaire. A sub-sample of 660 men reporting that they last used a condom for penile-vaginal sex (within the past three months) was analysed. Nine condom use errors/problems were assessed. Multivariate analyses controlled for men's age, marital status, and level of experience using condoms. RESULTS: Men's unilateral decision-making was associated with increased odds of removing condoms before sex ended (adjusted odds ratio (AOR) 2.51, p = 0.002), breakage (AOR 3.90, p = 0.037), and slippage during withdrawal (AOR 2.04, p = 0.019). Men's self-reported level of experience using condoms was significantly associated with seven out of nine errors/problems, with those indicating less experience consistently reporting more errors/problems. CONCLUSIONS: Findings suggest that female involvement in the decision to use condoms for penile-vaginal sex may be partly protective against some condom errors/problems. Men's self-reported level of experience using condoms may be a useful indicator of the need for education designed to promote the correct use of condoms. Education programmes may benefit men by urging them to involve their female partner in condom use decisions.

Breakage, slippage and acceptability outcomes of a condom fitted to penile dimensions.

OBJECTIVE: This study compared failure rates of a standard-sized condom and a condom fitted to a man's penile length and circumference and assessed users' perceptions of condom acceptability and confidence in the efficacy of both condoms. METHOD: Using an experimental crossover design with Internet-based daily diaries, 820 men who wore at least one of each condom type reported outcomes and perceptions of condoms used during vaginal and anal intercourse events for which they were the insertive partner. RESULTS: Breakage for fitted condoms (0.7%) was significantly less than for standard-sized condoms (1.4%). When assessed by penile dimensions, significantly less breakage of fitted condoms than standard-sized condoms was observed among men in the middle circumference category (12-13 cm) during anal intercourse (1.2% versus 5.6%), men in the larger circumference category (> or =14 cm) during vaginal intercourse (0.6% versus 2.6%), and men in the longer length category (> or =16 cm) for both vaginal (0.5% versus 2.5%) and anal (3.0% versus 9.8%) intercourse. More slippage upon withdrawal after vaginal intercourse occurred with fitted condoms among men in the middle penile length (1.9% versus 0.9%) and circumference (2.2% versus 0.7%) categories. CONCLUSIONS: Fitted condoms may be valuable to sexually transmitted infection prevention efforts, particularly for men with larger penile dimensions. That fitted condoms slipped more for some men provides insights into the need for unique educational materials to accompany such products. Findings also highlight the need for participatory approaches between public health, condom manufacturers, and the retail industry to integrate fitted products into our work successfully.

Men with broken condoms: who and why?

OBJECTIVES: To identify (1) the prevalence of condom breakage, and demographic and sexuality-related differences among young men who have sex with women reporting and not reporting this event; (2) condom-specific behaviours associated with breakage. METHODS: Young men (n = 278) attending a clinic for treatment of sexually transmitted infections (STIs) responded to an anonymous questionnaire aided by a CD recording of the questions. The samples were screened to include only men who had used a condom during penile-vaginal sex at least three times in the past 3 months. Condom-specific behaviours (including breakage) were assessed using these last three acts of condom use as the recall period. Correlates achieving bivariate significance were subjected to multivariate analysis. RESULTS: Nearly one third (31.3%) of the men reported recent breakage. The breakage rate was 15%. Three correlates significantly distinguished between men who did and did not report breakage. Men who had past STIs were more likely to report breakage (adjusted odds ratio (AOR) 2.08), as were men who also reported condom slippage (AOR 2.72). Less self-efficacy for correct condom use was also significantly associated with breakage (AOR 1.07). Further, three condom-specific behaviours were significantly associated with breakage: allowing condoms to contact sharp objects (AOR 2.6), experiencing problems with the "fit or feel" of condoms (AOR 2.3) and not squeezing air from the receptacle tip (AOR 2.0). CONCLUSIONS: Breakage may be common and may occur in a larger context of difficulties with condoms. STI clinics could potentially benefit some men by providing instructions on the correct use of condoms.

Molecular epidemiology of enterovirus 71 over two decades in an Australian urban community.

Enterovirus 71 (EV71), first isolated in 1969, has been responsible for numerous outbreaks of hand, foot and mouth disease (HFMD) with a small proportion of cases associated with neurological disease. Since 1997 there has been a significant increase in both the prevalence and virulence of EV71 in the Asia-Pacific region. We have examined the genetic diversity of EV71 in a large Australian city (Sydney N.S.W.) over a nineteen-year period. We determined the VP1 gene sequence of forty-eight EV71 strains isolated between 1983 and 2001. Analysis by molecular phylogeny revealed the presence of four subgenogroups B2, B4, C1 and C2. The results indicate that the major lineage circulating in Sydney N.S.W. was subgenogroup C1 with a recent switch in dominance to B4 in 2000 and 2001.

Assessment of condom use in men and women.

Self-reported condom use is a key variable in surveys of sexual behavior and in studies evaluating interventions to reduce the risk of sexually transmitted infections. This article provides a review of how male condom use has been assessed in research. We critically review a number of methodological issues, including the length of the recall period, terminology, specification of partner variables, validity and reliability of condom use, and use of newer data collection methods such as daily diaries and computer-assisted and online technologies. Assessment of condom use errors and problems, and the role of women in condom use are discussed. Finally, we offer recommendations for improving assessment of condom use in future research.

If the condom fits, wear it: a qualitative study of young African-American men.

OBJECTIVE: To extend the current knowledge base pertaining to condom failure among young African-American men by assessing their experiences with male condom use. METHODS: Qualitative assessments were conducted with 19 African-American men (aged 18-29 years) who had just been diagnosed with an STI and reported using condoms in the previous 3 months. RESULTS: Five categories were identified from the data. These categories pertained to: (1) the "fit and feel" of condoms; (2) condom brand and size; (3) application problems; (4) availability of condoms and lubricants; and (5) commitment to condom use. Common themes included reasons why men believed condoms would break or slip off during sex. Comfort problems, including tightly fitting condoms and condoms drying out during intercourse, were mentioned frequently. Condom associated erection problems were often described. Many men also noted that condom use reduced the level of sexual satisfaction for their female partners. Men noted that finding the right kind of condom was not always easy and it became apparent during the interviews that men typically did not acquire lubrication to add to condoms. Despite their expressed problems with using condoms, men were, none the less, typically emphatic that condom use is an important part of their protective behaviour against STIs. CONCLUSION: Men were highly motivated to use condoms; however, they experienced a broad range of problems with condom use. With the exception of losing the sensation of skin to skin contact, the vast majority of these problems may be amenable to behavioural interventions.

A prospective study of the effects of oral contraceptives on sexuality and well-being and their relationship to discontinuation.

The purpose of the study was to explore predictors of discontinuation of oral contraceptives (OC) including pre-OC use characteristics and adverse physical, emotional, and sexual effects of OCs. Women aged 18+ years in committed, sexually active relationships were assessed before starting OC and reassessed at 3, 6, and 12 months or shortly after discontinuation. Assessment included pre-OC use attitudes and expectations about the pill; self-reported side effects and perimenstrual symptoms including premenstrual syndrome (PMS); physical and emotional well-being; and sexual interest, enjoyment, and frequency of sexual activity. Seventy-nine women completed the study, 38% continued OCs, 47% discontinued, and 14% switched to another OC. Emotional side effects, worsening of PMS, decreased frequency of sexual thoughts, and decreased psychosexual arousability correctly categorized 87% of cases by using logistic regression. Emotional and sexual side effects were the best predictors of discontinuation/switching, yet such OC effects have been largely ignored in the research literature.

Better psychological functioning and higher social status may largely explain the apparent health benefits of wine: a study of wine and beer drinking in young Danish adults.

BACKGROUND: Findings from a recent series of Danish studies suggest that moderate wine drinkers are healthier than those who drink other alcoholic beverages or those who abstain. OBJECTIVE: To identify possible explanatory factors associated with the health benefits of wine consumption through the examination of a wide spectrum of social, cognitive, and personality characteristics related to both beverage choice and health in young Danish adults. SUBJECTS AND METHODS: Descriptive cross-sectional study of characteristics associated with beverage choice in a sample of 363 men and 330 women between the ages of 29 and 34 years, selected from the Copenhagen Perinatal Cohort on the basis of perinatal records. MAIN OUTCOME MEASURES: Socioeconomic status, education, IQ, personality, psychiatric symptoms, and health-related behaviors, including alcohol consumption, were analyzed. The outcome variables were subjected to linear and logistic regression analyses with 2 factors (beer and wine), each with 2 levels (drinking or not drinking a certain beverage type). RESULTS: Wine drinking was significantly associated with higher IQ, higher parental educational level, and higher socioeconomic status. Beer drinking was significantly associated with lower scores on the same variables. On scales concerning personality, psychiatric symptoms, and health-related behaviors, wine drinking was associated with optimal functioning and beer drinking with suboptimal functioning. CONCLUSIONS: Our data demonstrate that wine drinking is a general indicator of optimal social, cognitive, and personality development in Denmark. Similar social, cognitive, and personality factors have also been associated with better health in many populations. Consequently, the association between drinking habits and social and psychological characteristics, in large part, may explain the apparent health benefits of wine.

Evaluation of NMR diffusion measurements for the conformational analysis of flexible peptides.

The use of diffusion coefficients measured with pulsed-field gradient NMR spectroscopy for the determination of the relative population of conformers in solutions of the human Growth Hormone peptide fragment, hGH(9-19), has been studied in aqueous and in trifluoroethanol (TFE)/ water solutions. The peptide is a good model compound for this study because it adopts a predominantly random coil conformation in aqueous solution and is helical in TFE. The results of the diffusion measurements suggest that the peptide exhibits predominantly random coil structures in aqueous solution and adopts a more helical conformation in solutions containing increasing mole fractions of TFE, consistent with the qualitative findings of the standard CD and NMR experiments to probe peptide conformation. These results indicate that diffusion coefficients measured with NMR can provide additional information about temperature- and solvent-induced changes in the extent of the helical conformer for hGH(9-19) in aqueous solution and in solutions containing various mole fraction of TFE, respectively.

Effects of fragrance on female sexual arousal and mood across the menstrual cycle.

The effects of fragrance on sexual response in women were investigated using subjective and physiological measures of sexual arousal and of mood. Responses were obtained from female participants in three different fragrance conditions (female fragrance, male fragrance, and a "blank" or neutral substance), as they viewed erotic and sexually neutral films, and fantasized about sexual situations. Each woman was tested twice: during the midfollicular and periovulatory phases of her menstrual cycle. Menstrual cycle phase effects were apparent; self-report data indicated greater sexual arousal and more positive mood during the periovulatory than during the follicular phase. Results demonstrated a positive effect of the male fragrance on genital arousal during erotic fantasy, but this finding was apparent only during the follicular phase testing session. This effect did not appear to be mediated by any effects of fragrance on mood.

The roles of two amino acid residues in the active site of L-lactate monooxygenase. Mutation of arginine 187 to methionine and histidine 240 to glutamine.

Lactate monooxygenase (LMO) catalyzes the conversion of L-lactate to acetate, CO(2), and water with the incorporation of molecular oxygen. Arginine 187 of LMO is highly conserved within the family of L-alpha-hydroxyacid oxidizing enzymes (Lê, K. H. D., and Lederer, F. (1991) J. Biol. Chem. 266, 20877-20881). By comparison with the equivalent residue in flavocytochrome b(2) from Saccharomyces cerevisiae (Pike, A. D., Chapman, S. K, Manson, F. D. C,. Reid, G. A. , Gondry, M., and Lederer, F. (1996) in Flavins and Flavoproteins (Stevenson, K. J., Massey, V., and Williams, C. H., Jr., eds) pp. 571-574, University of Calgary Press, Calgary, AB, Canada), arginine 187 might be expected to have an important role in catalytic efficiency and substrate binding in LMO. Histidine 240 is predicted to be close to the substrate binding site of LMO, although it is not conserved within the enzyme family. Arginine 187 has been replaced with methionine (R187M), and histidine 240 has been replaced with glutamine (H240Q). L-Lactate oxidation by R187M is very slow. The binding of L-lactate to the mutant enzyme appears to be very weak, as is the binding of oxalate, a transition state analogue. The binding of pyruvate to the reduced enzyme is also very weak, resulting in complete uncoupling of enzyme turnover, with H(2)O(2) and pyruvate as the final products. In addition, anionic forms of the flavin are unstable. The K(d) for sulfite is increased nearly 400-fold by this mutation. The semiquinone form of R187M is also thermodynamically unstable, although the overall midpoint potential for the two-electron reduction of R187M is only 34 mV lower than for the wild-type enzyme. H240Q more closely resembles the wild-type enzyme. The steady-state activity of H240Q is completely coupled. The k(cat) is similar to that for the wild-type enzyme.

Role of the flavin midpoint potential and NAD binding in determining NAD versus oxygen reactivity of xanthine oxidoreductase.

Xanthine oxidoreductase from bovine milk can be prepared in two interconvertible forms, xanthine oxidase (XO) and xanthine dehydrogenase (XDH), depending on the number of protein cysteines versus cystines. Enzyme forms differ in respect to their oxidizing substrates; XDH prefers NAD to molecular oxygen, whereas XO only reacts significantly with oxygen. The preference for oxidizing substrate is partially explained by thermodynamics. Unlike XDH, the midpoint potential of the FAD, the center at which oxygen and NAD react, is too high in XO to efficiently reduce NAD (Hunt, J., Massey, V., Dunham, W.R., and Sands, R.H. (1993) J. Biol. Chem. 268, 18685-18691). To distinguish between changes in thermodynamics and in substrate binding, samples of both XO and XDH have been prepared in which the native FAD has been replaced with an FAD analog of different redox potential, 1-deaza-FAD or 8-CN-FAD. Reductive titrations indicate that both 1-deaza-XO and 1-deaza-XDH have a flavin midpoint potential similar to native XDH and that 8-CN-XO and 8-CN-XDH each have a flavin potential higher than XO. Both the low potential 1-deaza-XO and the high potential 8-CN-XDH contain essentially no xanthine/NAD activity. However, 1-deaza-XDH does exhibit xanthine/NAD activity, and 8-CN-XO has normal xanthine/oxygen activity. The binding of NAD to oxidized XO and XDH was investigated by ultrafiltration and isothermal titration calorimetry. The Kd for the binding of NAD to XDH was determined to be 280 +/- 145 microM by ultrafiltration and 160 +/- 40 microM by isothermal titration calorimetry. No evidence for the binding of NAD to XO by either method could be obtained. A low flavin midpoint potential is necessary but not sufficient for dehydrogenase activity.

Would you say you "had sex" if...?

CONTEXT: The current public debate regarding whether oral sex constitutes having "had sex" or sexual relations has reflected a lack of empirical data on how Americans as a population define these terms. OBJECTIVE: To determine which interactions individuals would consider as having "had sex." METHODS: A question was included in a survey conducted in 1991 that explored sexual behaviors and attitudes among a random stratified sample of 599 students representative of the undergraduate population of a state university in the Midwest. PARTICIPANTS: The participants originated from 29 states, including all 4 US Census Bureau geographic regions. Approximately 79% classified themselves as politically moderate to conservative. MAIN OUTCOME MEASURE: Percentage of respondents who believed the interaction described constituted having "had sex." RESULTS: Individual attitudes varied regarding behaviors defined as having "had sex": 59% (95% confidence interval, 54%-63%) of respondents indicated that oral-genital contact did not constitute having "had sex" with a partner. Nineteen percent responded similarly regarding penile-anal intercourse. CONCLUSIONS: The findings support the view that Americans hold widely divergent opinions about what behaviors do and do not constitute having "had sex."

Reduced cadherin/catenin complex expression in celiac disease can be reproduced in vitro by cytokine stimulation.

Celiac disease is characterized by a chronic immune response to dietary gluten, in which T cell responses result in elevated mucosal levels of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1, interferon (IFN)-gamma, and transforming growth factor (TGF)-beta, which induce profound mucosal remodeling associated with increased enterocyte proliferation, apoptosis, and migration. Reduced intestinal expression of the morphoregulatory cell adhesion molecule E-cadherin, which forms complexes with beta-catenin, can increase enterocyte proliferation and migration. However, its mechanism of action in gastrointestinal inflammatory conditions and any involvement in celiac disease is unknown. In this study, we describe changes in E-cadherin and beta-catenin expression in celiac disease tissue and determine the effect of cytokines on their expression in an in vitro model. We assessed E-cadherin and beta-catenin expression in intestinal biopsies from 24 patients with celiac disease, 12 patients with treated celiac disease, and 10 healthy patients by immunohistochemistry, Western blotting, and confocal microscopy. Using Caco-2 cells, we examined the effect of TNF-alpha, IL-1, IFN-gamma, and TGF-beta on E-cadherin expression. E-cadherin transcription was assessed in both intestinal biopsies and Caco-2 cells by in situ hybridization and RT-PCR, respectively. A marked reduction in protein expression of E-cadherin and beta-catenin that returns to normal levels after treatment was observed in celiac disease; this reduction was associated with reduced levels of E-cadherin mRNA. E-cadherin expression in Caco-2 cells was significantly reduced after TNF-alpha, IL-1, and IFN-gamma stimulation. The effect of TNF-alpha on E-cadherin expression was maximal after stimulation for 48 hours and also induced modest reductions in beta-catenin expression. The action of TNF-alpha on E-cadherin was reversible and was shown to act at the transcriptional level. These results demonstrate the novel findings that E-cadherin and beta-catenin expression are reversibly down-regulated in celiac disease and that such changes in epithelial cadherin/catenin complexes may be mediated by cytokines acting on cadherin transcription.