The case for wider use of testing for HIV infection.
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AIDS Serodiagnosis↗
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A cluster of HIV infection among heterosexual people without apparent risk factors.
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Adult↗
Cloning of an Alpha-TFEB fusion in renal tumors harboring the t(6;11)(p21;q13) chromosome translocation.
MITF, TFE3, TFEB, and TFEC comprise a transcription factor family (MiT) that regulates key developmental pathways in several cell lineages. Like MYC, MiT members are basic helix-loop-helix-leucine zipper transcription factors. MiT members share virtually perfect homology in their DNA binding domains and bind a common DNA motif. Translocations of TFE3 occur in specific subsets of human renal cell carcinomas and in alveolar soft part sarcomas. Although multiple translocation partners are fused to TFE3, each translocation product retains TFE3's basic helix-loop-helix leucine zipper. We have identified the genes fused by the chromosomal translocation t(6;11)(p21.1;q13), characteristic of another subset of renal neoplasms. In two primary tumors we found that Alpha, an intronless gene, rearranges with the first intron of TFEB, just upstream of TFEB's initiation ATG, preserving the entire TFEB coding sequence. Fluorescence in situ hybridization confirmed the involvement of both TFEB and Alpha in this translocation. Although the Alpha promoter drives expression of this fusion gene, the Alpha gene does not contribute to the ORF. Whereas TFE3 is typically fused to partner proteins in subsets of renal tumors, we found that wild-type, unfused TFE3 stimulates clonogenic growth in a cell-based assay, suggesting that dysregulated expression, rather than altered function of TFEB or TFE3 fusions, may confer neoplastic properties, a mechanism reminiscent of MYC activation by promoter substitution in Burkitt's lymphoma. Alpha-TFEB is thus identified as a fusion gene in a subset of pediatric renal neoplasms.
Base Sequence↗
The K protein domain that recruits the interleukin 1-responsive K protein kinase lies adjacent to a cluster of c-Src and Vav SH3-binding sites. Implications that K protein acts as a docking platform.
The heterogeneous ribonucleoprotein particle (hnRNP) K protein interacts with multiple molecular partners including DNA, RNA, serine/threonine, and tyrosine kinases and the product of the proto-oncogene, Vav. The K protein is phosphorylated in vivo and in vitro on serine/threonine residues by an interleukin 1 (IL-1)-responsive kinase with which it forms a complex. In this study we set out to map the K protein domains that bind kinases. We demonstrate that the K protein contains a cluster of at least three SH3-binding sites (P1, PPGRGGRPMPPSRR, amino acids 265-278; P2, PRRGPPPPPPGRG, 285-297; and P3, RARNLPLPPPPPPRGG, 303-318) and that each one of these sites is capable of selectively engaging c-Src and Vav SH3 domains but not SH3 domains of Abl, p85 phosphatidylinositol 3-kinase, Grb-2, and Csk. We demonstrate that the K protein domain that recruits and is phosphorylated in an RNA-dependent manner by the IL-1-responsive kinase, designated KPK for K protein kinase, is contained within the 338-425-amino acid stretch and thus is contiguous but does not include the cluster of the SH3-binding sites. K protein and KPK co-immunoprecipitate from cell extracts with either c-Src or Vav, suggesting that K protein-KPK-c-Src and K protein-KPK-Vav complexes exist in vivo. Furthermore, in the context of K protein, c-Src can reactivate KPK in vitro. The succession of kinase-binding sites contained within the K protein that allow it to form multienzyme complexes and facilitate kinase cross-talk suggest that K protein may serve as a docking platform that promotes molecular interactions occurring during signal transduction.
Amino Acid Sequence↗
Biochemical characterization of the human cyclin-dependent protein kinase activating kinase. Identification of p35 as a novel regulatory subunit.
The activation of cyclin-dependent protein kinases (Cdks) is dependent upon site-specific phosphorylation and dephosphorylation reactions, as well as positive and negative regulatory subunits. The human Cdk-activating protein kinase (Cak1) is itself a Cdc2-related cyclin-dependent protein kinase that associates with cyclin H. The present study utilized specific anti-Cak1 antibodies and immunoaffinity chromatography to identify additional Cak1-associated proteins and potential target substrates. Immunoprecipitation of metabolically labeled human osteosarcoma cells revealed a number of Cak1-associated proteins, including p95, p37 (cyclin H), and a 35-kDa protein that was further characterized herein. Microsequence analysis obtained after limited proteolysis revealed peptide fragments that are similar, but not identical to, human and yeast cyclins, thus identifying p35 as a cyclin-like regulatory subunit. The greatest sequence similarity of human p35 is with Mcs2, a yeast cyclin that is essential for cell cycle progression. Immunoaffinity chromatography performed under nondenaturing conditions afforded the isolation of enzymatically active Cak1 from cell lysates, enabling studies of kinase autophosphorylation and comparative substrate utilization. Immunoaffinity-purified Cak1 phosphorylated monomeric Cdc2 and Cdk2, but not Cdk4; the phosphorylation of both Cdc2 and Cdk2 were increased in the presence of recombinant cyclin A. These studies indicate that the Cak1 catalytic subunit, like Cdc2 and Cdk2, associates with multiple regulatory partners and suggests that subunit composition may be an important determinant of this multifunctional enzyme.
Amino Acid Sequence↗
Growth hormone, interferon-gamma, and leukemia inhibitory factor utilize insulin receptor substrate-2 in intracellular signaling.
In this report, we demonstrate that insulin receptor substrate-2 (IRS-2) is tyrosyl-phosphorylated following stimulation of 3T3-F442A fibroblasts with growth hormone (GH), leukemia inhibitory factor and interferon-gamma. In response to GH and leukemia inhibitory factor, IRS-2 is immediately phosphorylated, with maximal phosphorylation detected at 15 min; the signal is substantially diminished by 60 min. In response to interferon-gamma, tyrosine phosphorylation of IRS-2 was prolonged, with substantial signal still detected at 60 min. Characterization of the mechanism of signaling utilized by GH indicated that tyrosine residues in GH receptor are not necessary for tyrosyl phosphorylation of IRS-2; however, the regions of GH receptor necessary for IRS-2 tyrosyl phosphorylation are the same as those required for JAK2 association and tyrosyl phosphorylation. The role of IRS-2 as a signaling molecule for GH is further demonstrated by the finding that GH stimulates association of IRS-2 with the 85-kDa regulatory subunit of phosphatidylinositol 3'-kinase and with the protein-tyrosine phosphatase SHP2. These results are consistent with the possibility that IRS-2 is a downstream signaling partner of multiple members of the cytokine family of receptors that activate JAK kinases.
3T3 Cells↗
Co-expression with BCR induces activation of the FES tyrosine kinase and phosphorylation of specific N-terminal BCR tyrosine residues.
The human BCR gene encodes a protein with serine/threonine kinase activity and regulatory domains for the small G-proteins RAC and CDC42. Previous work in our laboratory has established that BCR is a substrate for c-FES, a non-receptor tyrosine kinase linked to myeloid growth and differentiation. Tyrosine phosphorylation led to the association of BCR with the RAS guanine nucleotide exchange complex GRB2-SOS in vivo via the GRB2 SH2 domain, linking BCR to RAS signaling (Maru, Y., Peters, K. L., Afar, D. E. H., Shibuya, M., Witte, O. N., and Smithgall, T. E. (1995) Mol. Cell. Biol. 15, 835-842). In the present study, we demonstrate that BCR Tyr-246 and at least one of the closely spaced tyrosine residues, Tyr-279, Tyr-283, and Tyr-289 (3Y cluster), are phosphorylated by FES both in vitro and in 32Pi-labeled cells. Mutagenesis of BCR Tyr-177 to Phe completely abolished FES-induced BCR binding to the GRB2 SH2 domain, identifying Tyr-177 as an additional phosphorylation site for FES. Co-expression of BCR and FES in human 293T cells stimulated the tyrosine autophosphorylation of FES. By contrast, tyrosine phosphorylation of BCR by FES suppressed BCR serine/threonine kinase activity toward the 14-3-3 protein and BCR substrate, BAP-1. These data show that tyrosine phosphorylation by FES affects the interaction of BCR with multiple signaling partners and suggest a general role for BCR in non-receptor protein-tyrosine kinase regulation and signal transduction.
14-3-3 Proteins↗
A proteomics approach to identify proliferating cell nuclear antigen (PCNA)-binding proteins in human cell lysates. Identification of the human CHL12/RFCs2-5 complex as a novel PCNA-binding protein.
Proliferating cell nuclear antigen (PCNA), a eukaryotic DNA replication factor, functions not only as a processivity factor for DNA polymerase delta but also as a binding partner for multiple other factors. To understand its broad significance, we have carried out systematic studies of PCNA-binding proteins by a combination of affinity chromatography and mass spectrometric analyses. We detected more than 20 specific protein bands of various intensities in fractions bound to PCNA-fixed resin from human cell lysates and determined their peptide sequences by liquid chromatography and tandem mass spectrometry. A search with human protein data bases identified 12 reported PCNA-binding proteins from both cytoplasmic (S100 lysate) and nuclear extracts with substantial significance and four more solely from the nuclear preparation. CHL12, a factor involved in checkpoint response and chromosome cohesion, was a novel example found in both lysates. Further studies with recombinant proteins demonstrated that CHL12 and small subunits of replication factor C form a complex that interacts with PCNA.
Base Sequence↗
Sexual behaviour of infertile Nigerian women.
The objective of this study is to examine the sexual behaviour of infertile women in Ile-Ife, Nigeria and to elucidate to what extent women seeking treatment for secondary infertility are at risk of sexually transmitted diseases. In a 1-year study period, 236 secondarily infertile women (cases) and 472 pregnant women (controls) were interviewed using detailed open-ended questionnaires. Infertile women were at a significant risk of having multiple sexual partners OR 3.80 (1.97-7.32), reproductive tract infections OR 8.52 (5.08-14.37), early age at first sexual intercourse OR 19.13 (92.45-29.47) and poor condom use OR 4.50 (2.01-9.31) compared to controls (pregnant women). The paper discusses the reasons for the above observations and made recommendations aimed at reducing the infections related infertility in this subregion.
Journal Article↗
Impact of post-abortion counselling in a semi-urban town of Western Nigeria.
This study is designed to evaluate the impact of post-abortion counselling in bringing about changes in sexual behaviour among patients who had treatment for an induced abortion and/or its complication in the department of gynaecology and obstetrics of Wesley Guild Hospital Ilesa and Folasola Specialist Hospital between January 1999 and December 2001. A structured questionnaire designed to evaluate the impact of counselling was administered to 108 patients, who formed part of 238 patients who had undergone induced abortion and who benefitted from the behavioural contract counselling technique. The results showed that the percentage of women using contraception increased from 30 (27.8%) to 53 (49.1%) at the time of interview. The number of subjects with multiple sexual partners fell from about 62 (58%) to 12 (11%). About 24 (45%) found access to contraception difficult. Major factors influencing contraceptive usage and change in behaviour include suffering experienced at the time of termination 26 (49%) and knowledge of contraception 19 (36%). The study advocates post-abortion counselling as a tool to increasing contraceptive usage in women and influencing behavioural changes positively towards health promotives measures.
Abortion, Induced↗
Sexual behaviour of secondary school adolescents in Ilesa, Nigeria: implications for the spread of STIs including HIV/AIDS.
This research examined the sexual behaviour and perception of the risk of HIV/AIDS and other sexually transmitted infections (STIs) among adolescents in Nigerian secondary schools. Quantitative data was collected from 450 senior secondary school 1 and 2 students who were selected from 5 of the 22 co-educational secondary schools in Ilesa using a multistage sampling technique. In addition qualitative data was collected by focus group discussion (FGD) with 8 groups (4 for each of the sexes) of ten randomly selected respondents from 4 other secondary schools. Sixty three per cent had had sexual intercourse. There was no statistically significant (p>0.05) difference between the genders [females (52.3%) males (77.8%)], although males appeared to be more sexually active. The median age at first intercourse was 12 years with a range of 6-19 years. Many of the respondents had multiple sexual partners. There is poor perception of the risk of sexually transmitted infections (STIs) including that of human immune deficiency virus (HIV). It was concluded that there is a high risk of the spread of STIs, including HIV/AIDS in the study population. In view of the high prevalence of sexual intercourse and the reproductive health problems associated with STI, HIV/AIDS, it is recommended that a structured family life education (FLE) curriculum should be instituted for all schools starting at an early age.
Adolescent↗
High-risk sex behavior among young street-recruited crack cocaine smokers in three American cities: an interim report. The Multicenter Crack Cocaine and HIV Infection Study Team.
Since crack cocaine appeared in urban areas in the United States in the mid-1980s, reports have suggested that crack smokers may be at increased risk of sexually transmitted diseases (STDs), including infection with HIV, because they have multiple sex partners, trade sex for money or drugs, and rarely use condoms. A cross-sectional survey is being conducted in urban neighborhoods in Miami, New York and San Francisco--where crack use is common--to explore these issues. Indigenous street outreach workers are recruiting men and women who are either current regular crack smokers or who have never smoked crack; each group is further stratified according to whether participants had ever injected drugs. Participants were interviewed about their sexual and drug-use practices. Overall, crack smokers, whether injectors or not, engaged in higher-risk sexual behaviors than nonsmokers, reported greater numbers of sex partners than nonsmokers, and were more likely than nonsmokers to have exchanged sex for money or drugs or to have had an STD. Differences between crack smokers and nonsmokers were generally greater among non-injectors than among injectors, and generally greater among women than among men. Condom use, although somewhat more common with paying than nonpaying partners, was infrequent overall. Most of the subjects had not been in substance abuse treatment in the preceding 12 months, and a majority had never been in substance abuse treatment. Education and prevention programs specifically targeted at crack smokers not currently in substance abuse treatment are needed to reach these high-risk persons.
Adult↗
Ethnic differences in HIV risk behaviors, self-perceptions, and treatment outcomes among women in methadone maintenance treatment.
This study examined the HIV risk profiles of White, African-American, and Latina women enrolled in the UCLA Enhanced Methadone Maintenance Project, a NIDA-funded research demonstration project with the goal of reducing risk of HIV infection and/or transmission. Each group demonstrated distinct patterns associated with family relationships, sources of income, sexual and injection behaviors, and self-perceptions, although they were similar in their employment, drug use, mental health, and criminal behavior histories. In general, Latinas were more likely to report familial influences and to display evidence of low self-esteem and self-efficacy, inconsistent condom use, and high-risk injection behavior. White women reported the highest levels of regular condom use at follow-up; however, they were the least likely to report safer injection practices. African-American women expressed the highest levels self-esteem, yet they reported more alcohol use at intake and crack cocaine use both before and after treatment entry. They showed the greatest gains in adopting safer injection practices and were the least likely to report multiple sex partners after treatment entry. These findings can be used to improve the potential of methadone maintenance treatment for HIV risk reduction for women and to aid in developing culturally sensitive treatment protocols.
Adult↗
Adolescent tobacco smoking and associated psychosocial health risk factors.
OBJECTIVE: To determine the relationship between tobacco smoking and psychosocial health risk factors in adolescents. DESIGN: An in-class survey of schoolchildren in the final grade of basic school and in all three grades of secondary school. SETTING: Four of the 11 secondary schools in Tartu, Estonia. SUBJECTS: 977 schoolchildren, ages ranging from 14 to 18. MAIN OUTCOME MEASURES: A questionnaire was developed to explore various psychosocial aspects of tobacco smoking behaviour. The 21-item Beck Depression Inventory was used to measure depression. RESULTS: In the total sample, smokers accounted for 24.5% of the girls and 26.5% of the boys, of which 13% of the girls and 19% of the boys were daily smokers. Not enjoying time spent with parents (OR = 0.6), skipping breakfast (OR = 1.3), frequent headache (OR = 1.3) and stomach-ache (OR = 1.4), dislike of school (OR = 0.7), using illicit drugs (OR = 5.0) and having multiple sexual partners (OR = 2.4) were all associated with daily smoking. Higher BDI scores were seen among adolescent smokers, particularly in girls and among pupils whose parents were non-smokers. The girls who smoked daily showed a higher risk of having suicidal thoughts (OR = 2.4) compared with non-smokers. CONCLUSION: Smoking by adolescents is an indicator of risk for depression, distress and risk-taking health-damaging behaviours.
Adolescent↗
Knowledge about AIDS and reported risk behaviors among black college students.
This study surveyed 975 undergraduates attending a large East Coast university during the spring semester of the 1987/88 academic year. A convenience sample of predominantly black students (94%) participated. Overall, knowledge of basic AIDS-related facts was satisfactory. Raw scores on the 25-item knowledge scale ranged from 7 to 25, with a mean of 20.5 (82%) and a mode of 22 (88%). Selected questions on how HIV is not transmitted, however, posed some problems for respondents. Less than 30% of respondents knew that the AIDs virus was not transmitted by insects; less than 80% knew that AIDS was not transmitted on toilet seats, through blood donations, kissing, and coughing. The survey also asked students whether they had ever engaged in certain behaviors that put them at risk of HIV infection. Approximately 17% of respondents had experienced anal intercourse, 6.5% reported use of heroin, 32.6% reported having had multiple sex partners, and 16% had been treated for a sexually transmitted disease. Students who reported engaging in high-risk behaviors had statistically significant lower mean knowledge scores than those who reported not engaging in those same high-risk behaviors. Results of the study support the need to increase efforts to deliver AIDS information specifically targeted to individuals who may be engaged in high-risk behaviors. Special health education programs must be designed to focus attention on risk behaviors (ie, unprotected anal intercourse) instead of risk groups (ie, homosexual and bisexual males).
Acquired Immunodeficiency Syndrome↗
Risk level, knowledge, and preventive behavior for human papillomaviruses among sexually active college women.
During the past decade, there has been mounting scientific evidence linking human papillomavirus (HPV) with cervical cancer and, at the same time, a great increase in physician consultations for HPV infections. HPV infection risk factors include multiple sex partners, early age at first intercourse, history of sexually transmitted diseases (STDs), and smoking. This study surveyed 263 sexually active college women and concluded that (1) they are at considerable risk for contracting HPV, (2) they lack awareness of HPV, and (3) they are not practicing preventive behaviors that could reduce their risk of HPV and its serious consequences.
Adolescent↗
Students' knowledge and behavior concerning safer sex: a UK study.
Most students in institutions of further and higher education in the northeast of England who responded to a 1989 survey dealing with sexual behavior and safer sex were heterosexual and had been sexually active or intended to have sexual intercourse. Many students, however, believed that safer sex implied having no sex at all or were unaware of the role of nonpenetrative sex in preventing human immunodeficiency virus (HIV) infection. They did not use condoms, in spite of having positive attitudes about condom use, and they engaged in one or more sexual activities that increased the risk of acquiring HIV infection. In view of the increasing incidence of acquired immunodeficiency syndrome (AIDS), the authors assert, these findings are cause for concern and require concerted action by health educators and society to encourage safer sex practices and to prevent the spread of HIV infection.
Acquired Immunodeficiency Syndrome↗
Knowledge, attitudes, and practices of breast and cervical cancer screening among Vietnamese women.
The Vietnamese are the fastest-growing Asian/Pacific Islander ethnic group in California. Data from Vietnam and elsewhere suggest that cervical cancer and breast cancer are major contributors to cancer morbidity and mortality among Vietnamese women. However, little is known about the cancer knowledge and screening practices of Vietnamese women. Using a structured 57-item written questionnaire, we conducted a mailed survey of 400 randomly selected Vietnamese adult women in San Francisco. Overall, 107 women responded (31%). Of the respondents, 54 (52%) indicated that there was little one could do to prevent cancer. More than a third (39%) thought that breast or cervical cancer could be caused by poor hygiene, and about one-third (29%) thought that these cancers could be contagious. Although virtually all (97%) had heard of cancer, one-third did not know that a breast lump could be a sign of breast cancer (37%) or that abnormal vaginal bleeding could be a sign of cervical cancer (39%). Many (55%) did not know that family history was a risk factor for breast cancer and three-fourths (74%) did not know that having multiple sexual partners was a risk factor for cervical cancer. Fourteen (13%) had not heard of breast self-examination. Of 31 women aged > or = 40, 10 (34%) had never had a mammogram, and of 92 women aged > or = 18, 50 (54%) had never had a Papanicolaou test.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗