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Syphilis, sex and crack cocaine: images of risk and morality.

A new epidemic of syphilis in the Portland, Oregon metropolitan region mirrors a national trend in the United States. The epidemic is centered in urban areas, is associated with heterosexual transmission, and disproportionately affects people of color, especially African-Americans. The epidemic has been linked to sexual activity among users of crack cocaine, and particularly to the practice of trading sex and crack. Here, we report an analysis of in-depth interviews of 40 respondents, of whom 31 have used crack cocaine, 12 have experience as professional sex workers (prostitutes), and 12 are confirmed recent syphilis cases or their sexual contacts. These respondents confirm that sexual activity involving multiple anonymous partners often takes place within the context of crack cocaine use. They also describe sexual activity among more casual users of the drug. But respondents present themselves as having maintained an adherence to common American values regarding cleanliness, mortality, and sexual behavior. They speak of choosing sex partners according to whether a prospective partner 'looks clean.' This image of cleanliness goes beyond simple bodily hygiene, and into the realm of judgement about moral character. A person is more likely to be judged clean if he or she is known to come from a nice family, has a pleasant demeanor, or appears concerned about self-control. Such people are seen as fundamentally decent, and therefore less likely to have syphilis, a disease associated with deterioration, tearing down, dirtiness and disordering. Thus, respondents use conceptions of cleanliness and morality in constructing definitions of high- and low-risk sexual behavior, as they negotiate a life that endangers their sense of moral control. In doing this, they invoke beliefs and values central to the dominant culture surrounding them. This points to the limits of defining crack cocaine users, and other communities of drug users, as being culturally different from the rest of us.

Black or African American↗

AIDS knowledge and risk behaviors among domestic clients of female sex workers in Bali, Indonesia.

This study investigated AIDS and STD knowledge, risk behaviors and condom use among clients of female commercial sex workers in Bali, Indonesia. Although these clients were varied in their socioeconomic status, they all tended to have low levels of knowledge concerning HIV and STD transmission and prevention, multiple sexual partners, low frequencies of condom use with these partners, and experienced frequent STDs. Although HIV sero-prevalence rates are currently low in Indonesia, clients of CSWs are at high risk of HIV transmission. Given their high mobility and frequent sexual encounters with CSWs in other parts of Indonesia, these men could well be agents of rapid spread of the virus throughout Indonesia. Interventions to prevent the spread of the HIV virus must be targeted not only to CSWs, but also to their clients. These interventions should include educational activities concerning AIDS and STD transmission and prevention, condom promotion, efforts to improve condom availability, and activities to strengthen the health sectors' STD diagnosis and treatment capabilities for both CSWs and their clients.

Acquired Immunodeficiency Syndrome↗

Pap smear screening for adolescents: rationale, technique, and follow-up.

Cervical cytologic abnormalities are increasingly prevalent in teenagers. Adolescents are at greater risk for cervical neoplasia than adult women because of the biologic changes occurring in the cervix during puberty, the prevalence of human papillomavirus, and the behavioral risk factors in this age group. Two behavioral risk factors are early age at first coitus and multiple sex partners. Human papillomavirus is widely believed to be the etiologic agent associated with the spectrum of cervical neoplasias. Papanicolaou smear technique, reporting, and management of abnormal smears in teens is explained.

Adolescent↗

The extra sex combs product contains WD40 repeats and its time of action implies a role distinct from other Polycomb group products.

The extra sex combs (esc) gene product is a transcriptional repressor of homeotic genes. Although it is classified in the Polycomb group (PcG) on the basis of phenotypic criteria, it is distinct from most other PcG repressors in its time of action during development. We describe the temporal profile of esc mRNA expression during embryogenesis and the stage-specific rescue of esc mutants with a heat shock-inducible esc cDNA transformation construct. Both experiments support the idea that esc product plays an early, transient role in repression of homeotic genes. We also present the sequence of a full-length esc cDNA. The predicted esc protein is composed primarily of multiple copies of a repeat motif, termed the WD40 repeat, which are likely used in protein-protein contact. We provide evidence that individual copies of the esc WD40 repeats are needed for function in vivo. We suggest that esc protein is an adaptor that binds to multiple protein partners and assists in the assembly or targeting of other PcG proteins.

Amino Acid Sequence↗

Tuberculosis and HIV infection association in a rural district of northern Uganda: epidemiological and clinical considerations.

59 (18.3%) of 323 patients with tuberculosis (TB) tested for HIV-1 antibody by ELISA technique (Wellcozyme) were seropositive. In the control group selected among the health personnel working in the Arua Hospital, 7.7% were found positive for HIV-1 antibody, thus showing a significantly lower prevalence compared with the TB patients (P < 0.005). The prevalence of HIV infection was 50% in the urban TB patients, 7% in TB patients living in rural areas surrounding Arua town and 1.6% in the peripheral rural setting. Of 27 TB patients with clinical AIDS, 18 died during the course of the study. The AIDS patients' survival rate was 46.4% 6 months after diagnosis, and 21.4% after 16 months, the median period of survival being 5.0 months. Risk factors, sputum conversion rate, clinical and radiological findings were analysed. No significant difference was found between seropositive and seronegative TB patients for clinical drug-related toxicity (P > 0.05).

Adolescent↗

Emergency department HIV testing and counseling: an ongoing experience in a low-prevalence area.

STUDY OBJECTIVE: Despite recommendations, emergency department (ED)-based HIV screening is not widespread, and feasibility studies are generally limited to settings with high HIV prevalence (>1%). This investigation was to evaluate an ongoing, publicly funded, ED-based HIV counseling and testing program in a low-prevalence area. METHODS: We reviewed a database of patients treated by an ED-based HIV counseling and testing program at a large, urban, teaching hospital for 1998 to 2002. ED patients at risk for HIV were targeted for standard serologic testing and counseling. Data were collected prospectively using standardized forms as part of clinical operations rather than in the context of rigorous research methodology; patient-oriented outcomes were not assessed. Counselors were trained according to Centers for Disease Control and Prevention guidelines, and health department guidelines for counseling and testing centers were followed. The main outcome measure was the number and proportion of patients newly diagnosed with HIV. RESULTS: Eight thousand five hundred seventy-four patients were approached; 5,504 consented to HIV testing. Mean age was 29 years (SD 9.4 years), 76% were black, and 50% were men. Five thousand three hundred seventy-four (97.6%) patients tested negative and 39 (0.7%) patients tested positive. Seventy-five percent of negative-test patients and 79% of positive-test patients were notified of test results. Information for seropositive patients not notified of results was forwarded to the health department. All notified HIV-positive patients entered treatment. Risk factors included sexually transmitted disease (47%), multiple sexual partners (40%), unprotected sex while using drugs or alcohol (30%), men having sex with men (5%), and intravenous drug use (4%). CONCLUSION: Identification of HIV-positive patients is possible in low-prevalence ED settings. In this instance, it was possible to perpetuate an ED-based HIV intervention program during an extended time. Although our work expands the profile of ED-based HIV counseling and testing beyond previous reports, the results should not be overgeneralized.

Adolescent↗

MLL-SEPT6 fusion transcript with a novel sequence in an infant with acute myeloid leukemia.

The MLL gene at 11q23 is a site of frequent rearrangement in acute leukemia with multiple fusion partners. A relatively uncommon rearrangement, associated with infant AML-M4, fuses the MLL and SEPT6 genes. SEPT6, located at Xq24, is a member of a family of mammalian septins involved in diverse functions such as cytokinesis, cell polarity, and oncogenesis. We describe the case of an infant with acute myelogenous leukemia who showed cytogenetic evidence of rearrangement between 11q23 and Xq24 regions. Fluorescence in situ hybridization analysis suggested a possible break in the MLL gene, and molecular analysis using reverse transcriptase-polymerase chain reaction followed by sequencing confirmed the expression of an MLL-SEPT6 fusion transcript with a novel sequence. The findings emphasize the importance of combined cytogenetic and molecular analyses in the workup of acute leukemia, especially in those leukemias that occur infrequently.

Base Sequence↗

HIV after age 55.

HIV/AIDS continues to increase among adults older than 50 years of age. Racial and ethnic minorities are still disproportionately affected by HIV/AIDS. The misconception that older adults are not at high risk for acquiring HIV/AIDS stems from a false impression that older adults are not sexually active and do not participate in risky behaviors that could result in HIV/AIDS. Studies show that older adult men and women engage in sexual intercourse--or some form of sexual behavior--at least weekly, and identify that risk factors for HIV/AIDS among adults older than 50 years of age include multiple sex partners, a high-risk partner, receipt of blood products between 1974 and 1984, or injection drug use. The development of new diagnostic resources, antimicrobial treatments, and antiretroviral therapy have made HIV/AIDS more chronic in nature, so that morbidity and mortality rates related to HIV/AIDS have declined. With this decline, HIV/AIDS has become a disease of chronicity rather than an acute illness.

Aged↗

Expert Consensus Conference. The screening for hepatitis C virus infection in adults in Italy, May 5-6, 2005.

A Consensus Conference was convened by the Italian National Institute of Health on May 5-6, 2005, to address the issue of the screening for hepatitis C virus infection in adults in Italy. It was concluded that a mass screening for hepatitis C virus infection is inappropriate. It was recommended that the following high-risk groups be tested for hepatitis C virus infection, particularly if they are potentially eligible for antiviral treatment: subjects with history of intravenous drug use; haemodialysis patients; subjects who received blood coagulation factors before 1987; subjects who received blood transfusions or organ transplantation before 1992; households of hepatitis C virus-infected individuals; subjects with multiple sexual partners which have or have had a sexually transmitted disease. A screening for hepatitis C virus infection was considered unjustified for persons who are scheduled for an invasive procedure (e.g. surgery, endoscopy) and during pregnancy.

Blood Transfusion↗

Three faces of mortalin: a housekeeper, guardian and killer.

Mortalin was first cloned as a mortality factor that existed in the cytoplasmic fractions of normal, but not in immortal, mouse fibroblasts. A decade of efforts have expanded its persona from a house keeper protein involved in mitochondrial import, energy generation and chaperoning of misfolded proteins, to a guardian of stress that has multiple binding partners and to a killer protein that contributes to carcinogenesis on one hand and to old age disorders on the other. Being proved to be an attractive target for cancer therapy, it also warrants attention from the perspectives of management of old age diseases and healthy aging.

Animals↗

[Hepatitis B and C virological tests: interpretation and practical results in women].

Chronic Hepatitis C or B infection can lead to liver cirrhosis and hepatocellular carcinoma. In women, these viral infections can be responsible for transmission to the spouse and to the child during delivery. Concerning the hepatitis C virus, the factors most strongly associated with infection are injection-drug use and blood transfusion before 1991. The risk of mother-to-infant transmission of hepatitis C virus is uncommon (5 per cent): except for the viral eradication before pregnancy, there is no preventive measure to propose. Pregnancy is not contra-indicated. Hepatitis C virus transmission by sexual contact in steady monogamous partnerships is low (< 1 per cent). In most developed parts of the world where the prevalence of chronic hepatitis B infection is low, most infections occur among high-risk adult populations including injection drug users and multiple heterosexual partners. On the contrary, in high prevalence areas, infection occurs during either the perinatal period or early in childhood. The risk of maternal-infant contamination is high, from 20 to 90 per cent according to the viral load. Vaccination prevents risk of infection and is strongly advised to persons at high risk of infection. Universal vaccination of infants is highly recommended.

DNA, Viral↗

The co-occurrence of substance use and high-risk behaviors.

Study findings suggest that alcohol and methamphetamine use heighten the risk for violence, multiple sexual partners, and unprotected sexual intercourse. Although the odds of engaging in risky behaviors increased dramatically with alcohol and methamphetamine use, the majority of subjects did not become involved in high risk behaviors even though they used alcohol and illicit drugs.

Adolescent↗

Identification of the key LMO2-binding determinants on Ldb1.

The overexpression of LIM-only protein 2 (LMO2) in T-cells, as a result of chromosomal translocations, retroviral insertion during gene therapy, or in transgenic mice models, leads to the onset of T-cell leukemias. LMO2 comprises two protein-binding LIM domains that allow LMO2 to interact with multiple protein partners, including LIM domain-binding protein 1 (Ldb1, also known as CLIM2 and NLI), an essential cofactor for LMO proteins. Sequestration of Ldb1 by LMO2 in T-cells may prevent it binding other key partners, such as LMO4. Here, we show using protein engineering and enzyme-linked immunosorbent assay (ELISA) methodologies that LMO2 binds Ldb1 with a twofold lower affinity than does LMO4. Thus, excess LMO2 rather than an intrinsically higher binding affinity would lead to sequestration of Ldb1. Both LIM domains of LMO2 are required for high-affinity binding to Ldb1 (K(D) = 2.0 x 10(-8) M). However, the first LIM domain of LMO2 is primarily responsible for binding to Ldb1 (K(D) = 2.3 x 10(-7) M), whereas the second LIM domain increases binding by an order of magnitude. We used mutagenesis in combination with yeast two-hybrid analysis, and phage display selection to identify LMO2-binding "hot spots" within Ldb1 that locate to the LIM1-binding region. The delineation of this region reveals some specific differences when compared to the equivalent LMO4:Ldb1 interaction that hold promise for the development of reagents to specifically bind LMO2 in the treatment of leukemia.

Adaptor Proteins, Signal Transducing↗

Acquired and genetic susceptibility to cervical cancer.

Infection with high-risk human papilloma virus (HPV) is a necessary risk factor for the development of cervical cancer (CC). However, there are many factors that contribute to the development of CC. We have been investigating the role of polymorphisms in chemical metabolizing genes and life-style factors in the development of CC between two countries with significantly different prevalence of CC. Our data confirm that infection with high-risk HPV is the most significant risk factor for CC in both Venezuela and US. In Venezuela, having multiple sex partners and early sexual activities are significant risk factors (OR=4.7, 95% CI=1.7-13.1; OR=6.7, 95% CI=2.3-20.1, respectively). On the other hand, cigarette smoking is the significant risk factor for women in the US (OR=6.4, 95% CI=1.8-23.2). Genotype analyses were conducted using specimens from the US population only. The GSTM1 null genotype was associated with a significant 3.4 fold increase in risk (95% CI=1.0-11.8) compared with those who were GSTM1 positive, after adjustment for smoking and HPV infection. Polymorphosis in CYP2E1 and mEH are associated with a non-significant increase in risk. Our study indicates that different acquired and genetic susceptibility factors can make significant contributions to the development of environmental disease such as cervical cancer.

Female↗

Urban-rural differences in the socioeconomic deprivation--sexual behavior link in Kenya.

We compare the impact of socioeconomic deprivation on risky sexual outcomes in rural and urban Kenya. Quantitative data are drawn from the Demographic & Health Surveys (DHS) and qualitative data from the Sexual Networking and Associated Reproductive and Social Health Concerns study. Using two separate indicators of deprivation we show that, although poverty is significantly associated with the examined sexual outcomes in all settings, the urban poor are significantly more likely than their rural counterparts to have an early sexual debut and a greater incidence of multiple sexual partnerships. The disadvantage of the urban poor is accentuated for married women; those in Nairobi's slums are at least three times as likely to have multiple sexual partners as their rural counterparts. The implications of these findings are discussed.

Adolescent↗

Modulation of agrin function by alternative splicing and Ca2+ binding.

The aggregation of acetylcholine receptors on postsynaptic membranes is a key step in neuromuscular junction development. This process depends on alternatively spliced forms of the proteoglycan agrin with "B-inserts" of 8, 11, or 19 residues in the protein's globular C-terminal domain, G3. Structures of the neural B8 and B11 forms of agrin-G3 were determined by X-ray crystallography. The structure of G3-B0, which lacks inserts, was determined by NMR. The agrin-G3 domain adopts a beta jellyroll fold. The B insert site is flanked by four loops on one edge of the beta sandwich. The loops form a surface that corresponds to a versatile interaction interface in the family of structurally related LNS proteins. NMR and X-ray data indicate that this interaction interface is flexible in agrin-G3 and that flexibility is reduced by Ca(2+) binding. The plasticity of the interaction interface could enable different splice forms of agrin to select between multiple binding partners.

Agrin↗

Coincidence detection in phosphoinositide signaling.

Phosphoinositide lipids function as both signaling molecules and as compartment-specific localization signals for phosphoinositide-binding proteins. In recent years, both phosphoinositides and phosphoinositide-binding proteins have been reported to display a restricted, rather than a uniform, distribution across intracellular membranes. Here, we examine recent data documenting the restricted distribution of both phosphoinositides and phosphoinositide-binding proteins and examine how phosphoinositide-binding proteins might engage multiple binding partners to achieve these restricted localizations, effectively acting as detectors of coincident localization signals.

Enzyme Activation↗

Life style, environmental and genetic susceptibility to cervical cancer.

We have studied cervical cancer (CC) patients from Venezuela and the US to elucidate the contribution of certain acquired and genetic susceptibility factors to the development of the disease. For acquired susceptibility factors, infection with high risk human papilloma virus (HPV), having multiple sex partners and having early sexual activities are significant risk factors for CC in Venezuela. The latter two are not significant risk factors for the US population. Infection with high risk HPV is a more significant risk factor for the US than the Venezuela populations. On the other hand, cigarette smoking is significantly associated with CC in the US but not the Venezuela populations. From genetic susceptibility factors, polymorphisms in the CYP2E1 and mEH genes are not associated with CC but the GSTM1 null genotype is for the US population. Our study indicates that the same susceptibility factors can have very different roles in the development of the same disease such as CC in different countries. The information is useful for the development of effective but different disease prevention programs for different countries in the control of CC.

Environment↗