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PubMed2004

An assessment of HIV/AIDS risk in higher education students in Yerevan, Armenia.

Armenia's current sociopolitical and economic instability and the alarming HIV incidence rates in neighboring countries amplify its risk for a national epidemic. The goals of this study were to assess HIV/AIDS knowledge and risk behaviors among higher education students in Yerevan. Knowledge of HIV transmission through sexual intercourse was markedly higher than that on intravenous transmission and prevailing myths; however, HIV/AIDS knowledge was not related to risk behaviors. Tobacco and alcohol prevalence was relatively high. Students reported risky sexual behaviors, including inconsistent condom use, casual sex, and multiple partners. In addition to descriptive statistics delineating gender differences across the target behavioral domains, bivariate and multivariate statistical analyses were used to understand factors that contributed to increased risk, including early age of initiation and the relationship between substance use and risky sexual activity. The study results provide much-needed information for the development of school- and community-based AIDS prevention programs in Armenia.

Acquired Immunodeficiency Syndrome↗

PubMed2004

A study of condom acceptability among men in an urban population in South India.

This study examines the acceptability of condoms to men from Chennai, South India. A sample of 150 male respondents who, in the main, had at least one risky sexual experience with a commercial sex worker or multiple partners was interviewed. The respondents included HIV-positive and HIV-negative individuals at sexually transmitted disease clinics, college students, and homosexuals. Awareness of condom usage was high, and 83% had used condoms at least once. The reasons for using condoms were protection from disease (43%), protection from AIDS (20%), and partner insistence (25%). Seventy-three percent of the respondents expressed dissatisfaction. Of those who used condoms for the first time, 72% were HIV negative, compared to 34% among those who did not use condoms. This indicates the need for developing the "condom habit," as using condoms at the first sexual experience is a strong predictor of future condom use.

Acquired Immunodeficiency Syndrome↗

PubMed2005

The relationship between violence exposure and HIV sexual risk behavior: does gender matter?

This study examined the association between violence exposures and HIV risk behaviors among 409 adolescents and whether such associations are gendered. Results indicated that adolescents exposed to either childhood sexual abuse or family or community violence were almost 3 and 4 times more likely, respectively, than peers not exposed to such violence to report a higher number of HIV-related risk behaviors. In addition, boys exposed to family violence were almost 3 times more likely than girls to report multiple partners and use of drugs during sex. Findings suggest a complex relationship among violence, gender, and HIV risks among adolescents.

Adolescent↗

PubMed2005

Conditional MLL-CBP targets GMP and models therapy-related myeloproliferative disease.

Chromosomal translocations that fuse the mixed lineage leukemia (MLL) gene with multiple partners typify acute leukemias of infancy as well as therapy-related leukemias. We utilized a conditional knockin strategy to bypass the embryonic lethality caused by MLL-CBP expression and to assess the immediate effects of induced MLL-CBP expression on hematopoiesis. Within days of activating MLL-CBP, the fusion protein selectively expanded granulocyte/macrophage progenitors (GMP) and enhanced their self-renewal/proliferation. MLL-CBP altered the gene expression program of GMP, upregulating a subset of genes including Hox a9. Inhibition of Hox a9 expression by RNA interference demonstrated that MLL-CBP required Hox a9 for its enhanced cell expansion. Following exposure to sublethal gamma-irradiation or N-ethyl-N-nitrosourea (ENU), MLL-CBP mice developed myelomonocytic hyperplasia and progressed to fatal myeloproliferative disorders. These represented the spectrum of therapy-induced acute myelomonocytic leukemia/chronic myelomonocytic leukemia/myelodysplastic/myeloproliferative disorder similar to that seen in humans possessing the t(11;16). This model of MLL-CBP therapy-related myeloproliferative disease demonstrates the selectivity of this MLL fusion for GMP cells and its ability to initiate leukemogenesis in conjunction with cooperating mutations.

Animals↗

PubMed2002

Anaplastic lymphoma kinase (ALK) activates Stat3 and protects hematopoietic cells from cell death.

The anaplastic lymphoma kinase (ALK) gene is characteristically translocated in Anaplastic Large Cell Lymphomas (ALCL) and the juxtaposition of the ALK gene to multiple partners results in its constitutive protein tyrosine kinase activity. We show here that expression of activated ALK induces the constitutive phosphorylation of Stat3 in transfected cells as well as in primary human ALCLs. Furthermore, immunohistochemical studies demonstrate that among distinct human B and T cell lymphomas, activation of Stat3 nuclear translocation is uniquely associated with ALK expression. NPM-ALK also binds and activates Jak3; however, Jak3 is not required for Stat3 activation or for cell transformation in vitro. Moreover, src family kinases are not necessary for NPM-ALK-mediated Stat3 activation or transformation, suggesting that Stat3 may be phosphorylated directly by ALK. To evaluate relevant targets of ALK-activated Stat3, we investigated the regulation of the anti-apoptotic protein Bcl-x(L) and its role in cell survival in NPM-ALK positive cells. NPM-ALK expression caused enhanced Bcl-x(L) transcription, largely mediated by Stat3. Increased expression of Bcl-x(L) provided sufficient anti-apoptotic signals to protect cells from treatment with specific inhibitors of the Jaks/Stat pathway or the Brc-Abl kinase. These studies support a pathogenic mechanism whereby stimulation of anti-apoptotic signals through activation of Stat3 contributes to the successful outgrowth of ALK positive tumor cells.

Anaplastic Lymphoma Kinase↗

PubMed2003

Mumbai disease in far western Nepal: HIV infection and syphilis among male migrant-returnees and non-migrants.

OBJECTIVE: To measure the seroprevalence of human immunodeficiency virus (HIV) infection and syphilis, and to assess the behavioural risk factors for these infections among migrant-returnees and non-migrants in far western Nepal. METHODS: In April 2001, we recruited 97 male migrant-returnees and 40 non-migrants from five rural villages in Doti district where migration to Mumbai is common. For data collection, we conducted a serological examination for HIV and syphilis, and a perception and behaviour survey on HIV and other sexually transmitted infections. RESULTS: We found that 11 of 137 men (8%) were positive for HIV infection and 30 men (22%) for syphilis. The respondents, especially the migrant-returnees from Mumbai, were engaging in risky behaviours such as pre- or extramarital sex, and sex with multiple partners, including sex workers. CONCLUSIONS: This study revealed high HIV and syphilis prevalence among the male migrant-returnees and non-migrants in far western Nepal where migration to Mumbai is common. The prevalent behaviours, particularly among the migrant-returnees, imply urgent needs of the behavioural modification programme in this area to prevent the spread of HIV infection to general population.

Acquired Immunodeficiency Syndrome↗

PubMed2002

Melanoma development and progression: a conspiracy between tumor and host.

While a genome-centric paradigm in human cancer development was useful for the understanding of some malignancies such as leukemias, causative molecular defects intrinsic to melanocytes have not been defined in the majority of human melanomas. Recent work, however, has shown that regulatory signals governing melanocytic cell growth and differentiation may originate from the surrounding host cells either directly through physical contact or indirectly through soluble factors and extracellular matrix molecules. In this review, we present experimental systems useful for dissecting melanoma-host interactions and highlight evidence that the tumor microenvironment contributes to the oncogenic process. Thus, melanomagenesis is not merely an act of a single outlaw but a conspiracy orchestrated by multiple partners in the neighborhood who come into play in a precise spatiotemporal order. Defining intercellular molecular dialogues in human skin promises to provide key information for the development of novel treatment strategies that target the functional unit of stroma and tumor.

Animals↗

PubMed2001

Pulmonary pathology in patients with AIDS: an autopsy study from Mumbai.

OBJECTIVE: Although India has a high prevalence of HIV/AIDS, the associated pathologies responsible for morbidity have not been evaluated previously in a representative study. Hence, an autopsy study was carried out to analyse the spectrum of pulmonary lesions in patients with HIV/AIDS. METHODS: A retrospective and prospective autopsy study was carried out during 1988-2000 at Mumbai, India. Lungs from 143 adults, with at least 10 sections from each case, were examined using routine and special stains. RESULTS: The risk factors for 97 men (68%) and 38 women (27%) included: heterosexual sex with multiple partners (135 cases, 95%); blood transfusions (three cases; 2%); sex between men (two cases; 1%); and unknown risk factors (three cases, 2%). Pulmonary pathology was observed in 126 (88%) cases. The lesions identified were tuberculosis (85 cases, 59%), bacterial pneumonia (26 cases, 18%), cytomegalovirus (CMV) infection (10 cases, 7%), cryptococcosis (eight cases, 6%), Pneumocystis carinii pneumonia (seven cases, 5%), aspergillosis (four cases, 3%), toxoplasmosis (two cases, 1%), Kaposi's sarcoma (one case, 1%), squamous cell carcinoma (one case, 1%). Two or more infections were observed in 18 (13%) cases. CONCLUSIONS: Pulmonary diseases and risk factors among patients with AIDS in India differ from those reported in industrialized countries. Tuberculosis was the most frequently observed pulmonary infection, followed by bacterial pneumonia and CMV pneumonitis. In contrast with industrialized countries, PCP remains less common in our patients. The information on opportunistic infections obtained in this study will be useful for managing HIV/AIDS cases at district level hospitals where diagnosing specific HIV-associated diseases is not always possible.

AIDS-Related Opportunistic Infections↗

PubMed2002

Prevention of spread of hepatitis C.

Hepatitis C virus (HCV) is transmitted by percutaneous or permucosal exposure to infectious blood or blood-derived body fluids. Based on the results of cohort and acute case control studies, risk factors associated with acquiring HCV infection in the United States have included transfusion of blood and blood products and transplantation of solid organs from infected donors, injecting drug use, occupational exposure to blood (primarily contaminated needle sticks), birth to an infected mother, sex with an infected partner, and multiple heterosexual partners. Nosocomial and iatrogenic transmission of HCV primarily are recognized in the context of outbreaks, and primarily have resulted from unsafe injection practices. Transmission from HCV-infected health care workers to patients is rare. Transfusions and transplants have been virtually eliminated as sources for transmission, and most (68%) newly acquired cases of hepatitis C are related to injecting drug use. The primary prevention of illegal drug injecting will eliminate the greatest risk factor for HCV infection in the United States. Other prevention strategies that need to be widely implemented include risk reduction counseling and services and review and improvement of infection control practices in all types of health care settings. Testing for HCV infection should be routinely performed for persons at high risk for infection or who require postexposure management. There are no recommendations for routine restriction of professional activities for HCV-infected health care workers, and persons should not be excluded from work, school, play, and child care or other settings on the basis of their HCV infection status.

Hepatitis C↗

PubMed2001

Predictors of the vaginal microflora.

OBJECTIVE: Our purpose was to define influences on the patterns of the vaginal microflora. STUDY DESIGN: We enrolled 617 African American and Mexican American women in a 1-year longitudinal study of sexual behaviors and the vaginal microflora on the basis of the presence of gonorrhea, chlamydial infection, trichomoniasis, or syphilis at the initial visit. The patients were assigned randomly to a behavioral intervention or standard counseling regarding sexually transmitted disease. We reevaluated 508 (82%) and 549 (89%) women at 6 and 12 months, respectively. A comprehensive survey of lower genital tract organisms was conducted at baseline and at 6 and 12 months. Behavioral and microbiologic associations were screened by bivariate analysis. All variables associated with an organism at P < or = .15 were included in a multivariate analysis. Associations between behavior and the genital tract microflora were identified by logistic regression coefficients with P <.05. RESULTS: African American race had a consistent association with vaginal microflora, specifically, Mycoplasma hominis, Trichomonas vaginalis, bacterial vaginosis, group B streptococci, Neisseria gonorrhoeae, and Chlamydia trachomatis. Various behaviors had a less consistent effect, including multiple partners, douching, frequency of coitus >3 times a week, and cunnilingus, fellatio, and anal intercourse at the last sexual encounter. M hominis (but not Ureaplasma urealyticum ), Gardnerella vaginalis, and Lactobacillus species were associated with bacterial vaginosis. Lactobacillus species appeared to protect against bacterial vaginosis and infection with G vaginalis. Sexually transmitted diseases (caused by M hominis, N gonorrhoeae, C trachomatis, and T vaginalis ) were associated with each other. In contrast, hormonal status, vaginal blood, and foreign bodies had little effect. CONCLUSION: The presence of other microorganisms and race have a more consistent association with the presence or absence of a cervical-vaginal organism than sexual behavior, hormonal status, vaginal devices, or the presence of abnormal vaginal bleeding.

Adolescent↗

PubMed2005

Structural mechanism for ubiquitinated-cargo recognition by the Golgi-localized, gamma-ear-containing, ADP-ribosylation-factor-binding proteins.

The Golgi-localized, gamma-ear-containing, Arf (ADP-ribosylation factor)-binding (GGA) proteins are clathrin adaptors that mediate the sorting of transmembrane-cargo molecules at the trans-Golgi network and endosomes. Cargo proteins can be directed into the GGA pathway by at least two different types of sorting signals: acidic cluster-dileucine motifs and covalent modification by ubiquitin. The latter modification is recognized by the GGAs through binding to their GAT [GGA and TOM (target of Myb)] domain. Here we report the crystal structure of the GAT domain of human GGA3 in a 1:1 complex with ubiquitin at 2.8-A resolution. Ubiquitin binds to a hydrophobic and acidic patch on helices alpha1 and alpha2 of the GAT three-helix bundle that includes Asn-223, Leu-227, Glu-230, Met-231, Asp-244, Glu-246, Leu-247, Glu-250, and Leu-251. The GAT-binding surface on ubiquitin is a hydrophobic patch centered on Ile-44 that is also responsible for binding most other ubiquitin effectors. The ubiquitin-binding site observed in the crystal is distinct from the Rabaptin-5-binding site on helices alpha2 and alpha3 of the GAT domain. Mutational analysis and modeling of the ubiquitin-Rabaptin-5-GAT ternary complex indicates that ubiquitin and Rabaptin-5 can bind to the GAT domain at two different sites without any steric conflict. This ability highlights the GAT domain as a hub for interactions with multiple partners in trafficking.

ADP-Ribosylation Factors↗

PubMed2002

Control of biochemical reactions through supramolecular RING domain self-assembly.

RING domains act in a variety of unrelated biochemical reactions, with many of these domains forming key parts of supramolecular assemblies in cells. Here, we observe that purified RINGs from a variety of functionally unrelated proteins, including promyelocytic leukemia protein, KAP-1TIF1beta, Z, Mel18, breast cancer susceptibility gene product 1 (BRCA1), and BRCA1-associated RING domain (BARD1), self-assemble into supramolecular structures in vitro that resemble those they form in cells. RING bodies form polyvalent binding surfaces and scaffold multiple partner proteins. Separation of RING bodies from monomers reveals that self-assembly controls and amplifies their specific activities in two unrelated biochemistries: reduction of 5' mRNA cap affinity of eIF4E by promyelocytic leukemia protein and Z, and E3 ubiquitin conjugation activity of BARD1:BRCA1. Functional significance of self-assembly is underscored by partial restoration of assembly and E3 activity of cancer predisposing BRCA1 mutant by forced oligomerization. RING self-assembly creates bodies that act structurally as polyvalent scaffolds, thermodynamically by amplifying activities of partner proteins, and catalytically by spatiotemporal coupling of enzymatic reactions. These studies reveal a general paradigm of how supramolecular structures may function in cells.

Animals↗

PubMed2000

Peptides selected to bind the Gal80 repressor are potent transcriptional activation domains in yeast.

The activation domain of the yeast Gal4 protein binds specifically to the Gal80 repressor and is also thought to associate with one or more coactivators in the RNA polymerase II holoenzyme and chromatin remodeling machines. This is a specific example of a common situation in biochemistry where a single protein domain can interact with multiple partners. Are these different interactions related chemically? To probe this point, phage display was employed to isolate peptides from a library based solely on their ability to bind Gal80 protein in vitro. Peptide-Gal80 protein association is shown to be highly specific and of moderate affinity. The Gal80 protein-binding peptides compete with the native activation domain for the repressor, suggesting that they bind to the same site. It was then asked if these peptides could function as activation domains in yeast when tethered to a DNA binding domain. Indeed, this is the case. Furthermore, one of the Gal80-binding peptides binds directly to a domain of the Gal11 protein, a known coactivator. The fact that Gal80-binding peptides are functional activation domains argues that repressor binding and activation/coactivator binding are intimately related properties. This peptide library-based approach should be generally useful for probing the chemical relationship of different binding interactions or functions of a given native domain.

Amino Acid Sequence↗

PubMed2001

NMR solution structure of murine CCL20/MIP-3alpha, a chemokine that specifically chemoattracts immature dendritic cells and lymphocytes through its highly specific interaction with the beta-chemokine receptor CCR6.

CCL20/MIP-3alpha is a beta-chemokine expressed in the thymus, skin, and intestinal epithelial cells that exclusively binds and activates the CCR6 receptor in both mice and humans. The strict receptor binding specificity of CCL20 is exceptional; other chemokines and their receptors bind promiscuously with multiple partners. Toward determining the structural basis for the selective receptor specificity of CCL20, we have determined its three-dimensional structure by 1H NMR spectroscopy. CCL20 exhibits the same monomeric structure previously described for other chemokines: a three-stranded beta-sheet and an overlying alpha-helix. The CCL20 receptor selectivity could arise from the rigid conformation of the N-terminal DCCL motif as well as the groove between the N-loop and the beta2-beta3 hairpin, which is significantly narrower in CCL20 than in other chemokines. Similar structural features are seen in human beta-defensin 2, a small nonchemokine polypeptide reported to selectively bind and activate CCR6, which stresses their importance for the specific binding of both CCL20 and beta-defensin 2 to CCR6. CCL20's structure will be useful to design tools aimed to modulate its important biological functions.

Amino Acid Motifs↗

PubMed2005

Perceptions of HIV risks and prevention strategies by rural and small city African Americans who use cocaine: views from the inside.

HIV/AIDS disproportionately affects African Americans, yet knowledge gaps exist regarding their views of risks and effective prevention strategies. This focus group study of rural and small city African Americans who use drugs sought to assess these perceptions. Common views of HIV risks included drug use, physical appearance as an indicator of HIV status, intentional transmission, having multiple partners, unprotected sex, bisexuality, and unfounded trust. Trading sex for drugs and unprotected sex when high were seen as drug use/HIV risk links, while HIV education and condom use were identified as ways to decrease risk. Perceptions of effective strategies included community-based programs, gender specific groups, providing food or other incentives, and making the program fun. Healthcare professionals and parents were viewed as the best people to promote HIV prevention. Based on the findings, effective intervention for this target group should encompass ethnocentric community-based strategies that focus on HIV education, condom use skills, and drug risk reduction.

Adolescent↗

PubMedDate not supplied

The context of sexually transmitted disease: life histories of woman abuse.

Approximately 25%-50% of women with sexually transmitted diseases (STDs), including AIDS, are involved in abusive relationships. Numerous characteristics associated with a past history of abuse are also risk factors for STD infection, including multiple partner relationships, substance abuse, early age at first coitus, and partner control of the relationship. Research has identified psychological effects of previous abuse, including depression, minimal control in relationships, and decreased self-efficacy. These effects may prevent abused women with STDs from making behavioral changes to prevent recurrence and transmission of disease. Life history methodology was used to understand the context of the interrelationships between STD and woman abuse in 30 Mexican American and African American women's lives. A focus on the context of abused women's partner relationships and aspects of personal control within these relationships may facilitate effective behavioral change, risk reduction, and subsequent decrease in incidence of STDs and woman abuse.

Adolescent↗

PubMed1996

Assessment of knowledge, attitudes, and behaviors relative to cervical cancer and the Pap smear among adolescent girls in West Virginia.

BACKGROUND AND METHODS: Questionnaires assessing knowledge of, attitudes toward, and behaviors relative to cervical cancer and its prevention were administered to 279 tenth-grade girls. RESULTS: Eighty-four percent had heard of cervical cancer, and 83% had heard of the Pap smear. Sexual intercourse with multiple partners and cigarette smoking were risk factors identified by 65% and 40% of these students, respectively. Forty-eight percent reported being sexually active. This group, compared with those not sexually active, was more likely to 1) identify the Pap test as a test involving a vaginal examination, 2) use tobacco products, and 3) be exposed to tobacco smoke. The most common barriers to obtaining a Pap test reported by those sexually active were embarrassment (64%), pain/discomfort (57%), fear of cancer (27%), fear of parents discovering sexual activity (25%), and cost (13%). CONCLUSIONS: Based on the information obtained in this study, the authors recommend changes in school health programs that target adolescent girls: 1) risk factors and behavior should receive more emphasis, and 2) the pelvic examination and Pap test should be described in sufficient detail to address the issues of embarrassment, pain, and discomfort.

Adolescent↗

PubMed2002

Sexual behaviour patterns and condom use in Tanzania: results from the 1996 Demographic and Health Survey.

We conducted this study to determine the factors associated with high-risk sexual behaviour and condom use among men and women who participated in the 1996 Tanzania Demographic and Health Survey (TDHS); and to assess changes in sexual behaviour between 1991/92 and 1996 TDHS. Respondents were regarded to have practised high-risk sexual behaviour if they were married or cohabiting and had other regular or non-regular sexual partners; or if they were unmarried and had non-regular partners or multiple regular partners. About 8% of women and 29% of men practised high-risk sexual behaviour. High-risk sexual behaviour was common among younger men and women, and decreased with increasing level of education in women. Respondents who were unmarried, Muslims and those who perceived themselves at increased risk of HIV/AIDS were more likely to practise high-risk sexual behaviour. About 4% of women and 15% of men reported to have used condoms during their last sexual encounter. Condom users were significantly more likely to practise high-risk sexual behaviour. Overall, no major changes in sexual behaviour and condom use were observed during the period between the two surveys. Predictors of high-risk sexual behaviour and condom use identified in this report provide valuable information that can be used to design targeted HIV/AIDS interventions in Tanzania.

Adolescent↗