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Multiple interactions with many different partners are responsible for the amazing functional versatility of proteins, especially those participating in cellular regulation. The structural properties that could facilitate multiple interactions are examined for small GTPases. The role of cellular constraints, compartmentation and scaffolds on protein-protein interactions is considered.
Trichomonas vaginalis infection in men is an important cause of nongonococcal urethritis. Effective detection of the parasite in men using culture requires examination of multiple specimens. We compared culture and PCR-enzyme-linked immunosorbent assay in urethral swabs, urine, and semen for T. vaginalis detection in male sexual partners of women with trichomoniasis identified by wet mount and culture. Trichomonads were detected by at least one positive test in 205/280 men (73.2%) who submitted at least one specimen for culture and PCR. Whereas InPouch TV culture detected only 46/205 cases (22.5%), PCR detected 201/205 (98.0%). Urethral swab cultures from men with urethritis were more likely to be positive with shorter incubation than specimens from men without urethritis. T. vaginalis was detected more often in men with wet-mount-positive partners. Even with a sensitive PCR assay, reliable detection of T. vaginalis in male partners required multiple specimens. The majority of male sexual partners in this study were infected, emphasizing the importance of partner evaluation and treatment.
A questionnaire study was conducted to assess the relationship between sexual regret and sexual behaviors and demographic factors among 348 college-aged students prior to attending an educational program about sexual health issues. Analyses conducted on the portion of the sample who were sexually active (n = 270) indicated that the majority (71.9%, n = 194) has regretted their decision to engage in sexual activity at least once. The most cited reasons for regret by students included their sexual decision making as inconsistent with their morals (37%), an acknowledgment that alcohol influenced their decision (31.7%), the realization they did not want the same thing as their partner (27.9%), the lack of condom use (25.5%), feeling pressure by their partner (23.0%), and their desire to wait until marriage to have sex (15.4%). The only significant sex difference was that women reported regret due to feeling pressured by a partner more often than men. Multiple and logistic regression analyses indicated that the only significant predictor of regret regarding one's sexual decisions was the number of sexual partners. These results demonstrate the need for sexual educators to incorporate sexual regret into their curricula as the phenomenon of regret is more common than pregnancy and sexually transmitted diseases, the usual focus of sexuality education.
Chromosomal translocations involving the immunoglobulin heavy chain (IGH) locus and various partner loci frequently are associated with multiple myeloma (MM). We investigated the expression profiles of the FGFR3/MMSET, CCND1, CCND3, MAF, and MAFB genes, which are involved in t(4;14)(p16.3;q32), t(11;14)(q13;q32), t(6;14)(p21;q32), t(14;16)(q32;q23), and t(14;20)(q32;q12), respectively, in purified plasma cell populations from 39 MMs and six plasma cell leukemias (PCL) by DNA microarray analysis and compared the results with the presence of translocations as assessed by dual-color FISH or RT-PCR. A t(4;14) was found in 6 MMs, t(11;14) in 9 MMs and 1 PCL, t(6;14) in 1 MM, t(14;16) in 2 MMs and 1 PCL, and t(14;20) in 1 PCL. In all cases, the translocations were associated with the spiked expression of target genes. Furthermore, gene expression profiling enabled the identification of putative translocations causing dysregulation of CCND1 (1 MM and 1 PCL) and MAFB (1 MM and 1 PCL) without any apparent involvement of immunoglobulin loci. Notably, all of the translocations were mutually exclusive. Markedly increased MMSET expression was found in 1 MM showing associated FGFR3 and MMSET signals on an unidentified chromosome. Our data suggest the importance of using combined molecular cytogenetic and gene expression approaches to detect genetic aberrations in MM.
A study of 759 cervical cancer patients, 1,430 controls, and 689 sex partners in four Latin American countries has made it possible to assess the influence of multiple factors upon the risk of invasive cervical cancer. The principal risk factors identified were the woman's age at first coitus, the number of her steady sex partners, her number of live births, the presence of DNA from human papillomavirus (HPV) types 16 or 18, a history of venereal disease, nonparticipation in early detection programs, and low socioeconomic status. There is good reason to believe that extensive detection programs directed mainly at high-risk groups in the Americas can reduce the high incidence of cervical cancer in this Region.
QUESTION: Post-exposure prophylaxis (PEP) is effective in preventing HIV infection after professional exposure. PEP is also recommended after inadvertent sexual exposure if two conditions are met: the source person is known to be HIV infected, and exposure to this person occurred only once or is accidental. The objective of this study is to describe the circumstances of sexual exposure and determine how frequently these conditions were present among patients diagnosed during primary HIV infection. METHODS: Physicians of 35 patients diagnosed with primary HIV infection provided detailed information on the circumstances of infection as well as on the patients and source persons. RESULTS: Most patients were homosexual (71%), and 91% were male. Only one patient (3%) had a single exposure with a known HIV-infected person and was therefore eligible for PEP. Eight patients (23%) who did not know the HIV status of their partner would have been eligible considering single exposure as a sufficient criterion for PEP. Oro-genital contact appears to account for transmission in four instances. Eleven persons (31%) were infected after sexual contact with their stable partner, of whom 7 did not known his/her HIV status. Twelve patients (34%) were infected after multiple unprotected sexual contact with unknown partners. CONCLUSION: The direct impact of PEP in terms of HIV infections prevented is likely to be small. PEP will not make up for the failure of other prevention methods. It may, however, contribute to the disclosure and the discussion of risk situations and help physicians provide individual counselling taking into account the precise context of risk behavior.
To characterize current risk behaviors of HIV drug abusers in the highly active antiretroviral therapy (HAART) era, socio-demographic, medical and behavioral information were obtained and immune measurements determined. High-risk sexual practices were prevalent. Participants diagnosed before 1995 were 6 times more likely to have unprotected sex with HIV+ partners (p = 0.05) and 11 times more likely to use contaminated needles (p = 0.05) than participants with later diagnosis. Consistent condom use was reported by only 7% of the cohort. Many (43%) of the participants reported multiple HIV+ and HIV- concurrent partners. Most (65%), particularly women (OR = 3, p = 0.02), did so for drugs or money. Despite detectable viral loads, 36% reported unprotected anal sex. Antiretroviral-treated men, compared to non-treated, tended to have unprotected anal sex (OR = 2, p = 0.07). The continued high-risk behaviors of HIV drug users, particularly those diagnosed before 1995 and/or on antiretroviral therapy, indicates an urgent need for new public health strategies.
Efavirenz (EFV) is a potent antiretroviral drug; its use may be limited, however, by psychiatric symptoms that require its discontinuation. We sought to identify the characteristics that placed patients at an elevated risk of discontinuation. Data for this cross-sectional study came from a self-administered questionnaire distributed by French AIDS community associations; it collected information about sociodemographic characteristics, addictive behaviours, treatment regimens, EFV history and depression. Patients remaining on EFV for more than six months were compared with those who stopped taking it. Of the 828 patients who completed the questionnaire, 175 had taken EFV for at least six months, and 152 had discontinued it (median months [IQR] of exposure=4[2-10]). Of these 327 patients (median age=42), 23% were women, 46% were unemployed, 38% had a steady sexual partner and 24% reported a history of multiple depressive episodes. Logistic regression showed that the factors independently associated with EFV discontinuation were female gender (OR[95%CI]=2.2[1.2-3.8]), unemployment (1.8[1.1-2.8]), a steady sexual partner (1.7[1-2.5]) and multiple episodes of depression (2.6[1.5-4.5]). Clinicians should keep in mind the neuropsychiatric risks of EFV during the first year, especially among patients with a history of multiple depressive episodes.
INTRODUCTION: The introduction of highly active antiretroviral therapy has relaunched the debate on risky sexual behavior among HIV-infected gay men. It was proposed to study the influences of lifestyle characteristics and health-related quality of life (HRQL) on unsafe sex with casual partners in a representative sample of HIV-infected gay men. METHODS: In 2003, a national survey based on face-to-face interviews was conducted among a representative sample of patients selected in a random stratified sample of 102 French hospital departments delivering HIV care. The patients selected for this analysis were gay men who reported having had sex with casual partners during the previous 12 months. Unsafe sex was defined as at least 1 episode of anal sexual intercourse without a condom with a casual partner during the previous 12 months. Health-related quality of life was assessed using the SF-36 Scale. Patients who declared that they had engaged in unsafe sex were compared with those who declared that they had not done so, using the chi test and logistic regressions. RESULTS: Among the 1,117 gay men who participated in the study, 607 declared having had casual partners during the previous 12 months, and 140 (20%) of this latter group had engaged in unsafe sex. Poor mental HRQL was encountered in 68% of the patients and found to be independently associated with unsafe sex, even after multiple adjustment for number of partners, occurrences of binge drinking, use of anxiolytics, use of the Internet, and use of outdoor and commercial venues for sexual encounters. CONCLUSIONS: Risky sexual behavior with casual partners is frequent among HIV-infected gay men. In addition to other well-known factors, behavior of this kind was found in this study to be related to poor mental HRQL. A more comprehensive approach to care designed to improve mental quality of life might therefore make for more effective secondary prevention.
This cross-sectional study analyses determinants of condom-use behaviour among patients attending dedicated STD clinics in South Africa. A structured interviewer-administered survey was conducted among 1473 patients. Patients' beliefs and attitudes towards condom use in general, as well as their personal condom-use behaviour were measured. Their perceptions, regarding the social influence of their partners and friends on their condom use, and of their self-efficacy in using condoms, while infected with an STD were also measured. Condom use, as a dependent variable, was examined and patients were placed in a pre-contemplation stage if they had never used a condom, contemplation if they had seriously thought of using a condom, some action stage if they sometimes used a condom and regular action stage if they used a condom every time. The relationships between the stages of change, as dependent variables, and the independent variables were investigated for both those patients with steady partners and those with outside partners. This was performed by stepwise multiple regression analyses. The variables that significantly explained stages of change were similar for patients with steady partners and those with outside partners. In both partner groups communication was the variable most strongly associated with the use of condoms. General self-efficacy in condom use, self-efficacy in condom use with a partner and attitudes towards the use of condoms played a role in determining patients' different stages of change.
OBJECTIVE: To determine factors associated with disclosure of human immunodeficiency virus (HIV)-positive status to sexual partners. METHODS: We interviewed 203 consecutive patients presenting for primary care for HIV at 2 urban hospitals. One hundred twenty-nine reported having sexual partners during the previous 6 months. The primary outcome of interest was whether patients had told all the sexual partners they had been with over the past 6 months that they were HIV positive. We analyzed the relationships between sociodemographic, alcohol and drug use, social support, sexual practice, and clinical variables; and whether patients had told their partners that they were HIV positive was analyzed by using multiple logistic regression. RESULTS: Study patients were black (46%), Latino (23%), white (27%), and the majority were men (69%). Regarding risk of transmission, 41% were injection drug users, 20% were homosexual or bisexual men, and 39% were heterosexually infected. Sixty percent had disclosed their HIV status to all sexual partners. Of the 40% who had not disclosed, half had not disclosed to their one and only partner. Among patients who did not disclose, 57% used condoms less than all the time. In multiple logistic regression analysis, the odds that an individual with 1 sexual partner disclosed was 3.2 times the odds that a person with multiple sexual partners disclosed. The odds that an individual with high spousal support disclosed was 2.8 times the odds of individuals without high support, and the odds that whites or Latinos disclosed was 3.1 times the odds that blacks disclosed. CONCLUSIONS: Many HIV-infected individuals do not disclose their status to sexual partners. Nondisclosers are not more likely to regularly use condoms than disclosers. Sexual partners of HIV-infected persons continue to be at risk for HIV transmission.
Female sexual partners of injection drug users are at risk for AIDS because of their association with street drug cultures and all their concomitant risks, including their own non-injecting drug use. This study examines a model of the social determinants of HIV-associated sexual risk behaviors. Multiple linear regression analysis was used to analyze the data for 207 female sexual partners who had never injected drugs. The findings show that crack cocaine use is the strongest contributor to the model, which explains fourteen percent of the variance of sexual risk behavior. The findings suggest that the risks associated with sexual practices are much greater for crack cocaine users than among non users of crack.
HIV-positive men face multiple challenges when deciding whether to disclose their serostatus to sex partners. The purpose of this literature review (1996-2004) is to identify valid and reliable research results that identify factors influencing serostatus disclosure to sex partners by men who are HIV-positive. Articles included in the review were identified through an electronic search using pertinent terms related to disclosure to sex partners, followed by a search of references for additional articles. A compilation of research results for 17 articles is presented under the headings of background, contextual, and psychosocial factors influencing disclosure. An analysis of the data suggests that differences in disclosure rates vary based on sex partner factors including serostatus, relationship status, and number of sex partners. Rates of disclosure to primary sex partners ranged from 67% to 88%, suggesting that nearly one third of main sex partners were not disclosed to and were at risk of contracting HIV, whereas a pattern of lower disclosure among casual partners was evident. As the number of sex partners increased, the likelihood of disclosure to all sex partners decreased, ranging from one quarter (25%) to slightly over half (58%). In addition, perceived efficaciousness and positive outcome expectations were the most frequent theoretical constructs embedded in the research associated with disclosure, suggesting that these factors play an important role in the process of disclosure to sex partners. Interpersonal factors that positively influenced self-disclosure included spousal support, emotional investment, and communication about safe sex, including asking about a partner's serostatus. Self-disclosure was not consistently associated with safer sex. Recommendations for future research are presented, based on the results included in this review.
Effective therapies are available for the treatment of infertility owing to specific causes. Most hormonal imbalances can be readily identified and successfully treated. The treatment of men with unexplained idiopathic infertility remains difficult. The availability of a multitude of agents ranging from hormones to nutritional supplements emphasizes the fact that none are consistently effective. There is no good way to predict which patients will respond to a specific treatment. Idiopathic infertility may result from multiple discrete defects in sperm generation and maturation that are as yet unidentified. A better understanding of these defects will yield more effective treatment options and appropriate triage of patients to specific therapeutic regimens. Assisted reproductive techniques remain an option for patients with idiopathic male infertility; however, they are expensive and treat the female partner for a male problem. Multiple gestations and other complications are not infrequent. Initial management should be directed at improving the quality of semen to facilitate natural conception. Specific abnormalities should be corrected. If empiric pharmacologic therapy is to be used, treatment should last at least 3 to 6 months to incorporate a full 74-day spermatogenic cycle. The infertile couple should be advised of the inconsistent response to therapy and the low conception rate that may follow when compared with the results of ART. When empiric therapy is decided upon, antiestrogens may be used and are effective in a subset of patients. The authors prefer to use clomiphene citrate, 25 mg per day. The dose may be increased to 50 or 75 mg to raise testosterone levels to the upper normal range. Lack of a significant improvement in semen parameters or of a pregnancy after a 3- to 6-month treatment period may be an indication to proceed with ART.
PURPOSE: Data were collected from a convenience sample of 550 detained adolescents (ages 14-18 years) to explore the association between adolescents' perception of teacher connectedness and a range of health risk behaviors, such as gang membership, use of in alcohol, drugs, and tobacco, and engagement in sexual risk behaviors prior to detainment. METHODS: Participants answered survey questions using audio-computer assisted self-interviewing procedures that assessed demographic, pro-social, problem, and drug and sexual risk behaviors. RESULTS: Multiple logistic regression analyses controlling for demographic and socioeconomic status, truancy, number of days in the detention center, and family factors indicated that adolescents who reported low teacher connectedness, relative to their peers reporting high teacher connectedness, were twice as likely to use marijuana and amphetamines, and twice as likely to be sexually active, have sex while high on alcohol or drugs, have a partner who was high on alcohol or other drugs during sex, and have multiple sexual partners. CONCLUSIONS: The association between teacher connectedness and adolescents' health risk behaviors prior to detainment suggests that school-based interventions that enhance the school environment, particularly teachers' skills and training to enhance and maximize the effectiveness of their student interactions, may be one strategy for reducing health risk behaviors and their associated adverse health outcomes among youth at high risk.
This study examines the relationships between exposure to violence and depression, hopelessness, and purpose in life among black adolescents living in or around public housing developments. Black adolescents (N = 225, males = 44%) ages 11 to 19 years in a southern city were administered an anonymous questionnaire. Depression was correlated with the exposure to violence (r = .28), family conflict (r = .29), and corporal punishment (r = .32) scales, perceived probability of being alive at age 25 years (r = -.14), socioeconomic status of head of household (r = .14), anticipated socioeconomic status as an adult (r = .21), and number of sexual partners (r = .22). Based on multiple regression analysis, corporal punishment, family conflict, educational level of head of household, and perceived probability of being alive at age 25 years explained 18% (p < or = .0001) of the variation in depression. Family conflict, corporal punishment, and unemployed head of household explained 11% of the variation in the hopelessness scale. Unemployed head of household, the corporal punishment scale, and number of sexual partners explained 9.7% of the variation in purpose in life. Even when accounting for other social factors, exposure to violence in the home was associated with psychological distress in this sample of adolescents.
Scribble (Scrib) is a large multi-domain cytoplasmic protein that was first identified through its requirement for the establishment of epithelial polarity. We tested the hypotheses that Scrib asssociates with the basolateral membrane via multiple domains, binds specific protein partners, and is part of a multimeric complex. We generated a series of EGFP-tagged Scrib fusion proteins and examined their membrane localizations in two types of polarized mammalian epithelial cells using biochemical and morphological approaches. We found that Scrib's Leucine-rich-repeat (LRR) and PDS-95/Discs Large/ZO-1 (PDZ) domains independently associate with the plasma membrane in both cell types. We identified multiple large Scrib complexes, demonstrated that Scrib and the cytoplasmic protein Lethal giant larvae2 (Lgl2) co-IP and that this association occurs via Scrib's LRR domain. Further, this report demonstrates that the membrane protein Vangl2 binds selectively to specific PDZ domains in Scrib. Our identification of Scrib's associations highlights its function in multiple biologic pathways and sets the stage for future identification of more proteins that must interact with Scrib's remaining domains. J. Cell. Biochem. 99: 647-664, 2006. (c) 2006 Wiley-Liss, Inc.
In vitro transformation of replicating myogenic cells by a variety of oncogenes is always accompanied by inhibition of the transition to the terminally differentiated state. Three main levels of interference by oncogenes may ultimately prevent transcription of skeletal muscle-specific genes. First, the transcription of muscle-regulatory factors (MRF) of the MyoD family can be extinguished in transformed myoblasts. Second, several oncoproteins are capable of silencing the transcriptional capacity of MRF. Third, the DNA binding activity of MRF can be negatively modulated by phosphorylation or competition by dominant negative partners. Oncogenes can function at multiple potential levels of regulation, depending on the myogenic cell context.