Biomedical subjects

S L Davies

Publications and source records attributed to S L Davies.

At least 19 recordsLinked to original sources

PubMed2002

Predictors of infection with Trichomonas vaginalis: a prospective study of low income African-American adolescent females.

OBJECTIVES: To identify psychosocial predictors of Trichomonas vaginalis infection among low income African-American adolescent females living in a high risk urban area of the United States. METHODS: Baseline plus 6 and 12 month follow up data collected as part of an HIV prevention intervention trial were utilised. The baseline sample consisted of 522 African-American females, 14-18 years of age. Recruitment sites were located in low income neighbourhoods of Birmingham, Alabama, characterised by high rates of unemployment, substance abuse, violence, teenage pregnancy, and sexually transmitted infections. Self administered vaginal swab specimens were cultured for T vaginalis. Baseline measures collected as part of a self administered survey and face to face interviews were used to predict subsequent infection with T vaginalis at any of the three assessment periods conducted over the span of 1 year. RESULTS: At baseline, 12.9% were diagnosed with T vaginalis. At the 6 and 12 month follow ups, T vaginalis was diagnosed in 8.9% and 10.2%, respectively. The strongest multivariate predictor of T vaginalis infection was biologically confirmed marijuana use; those using marijuana were more than six times as likely to test positive for T vaginalis (adjusted odds ratio (AOR) = 6.2, p = 0.0003). Other multivariate predictors were reporting that typical sex partners were at least 5 years older (AOR = 2.6; p = 0.005), reporting sex with non-steady partners (AOR = 1.9; p = 0.02), and history of delinquency (AOR = 1.3; p = 0.02). The odds of testing positive increased by 31% for every one unit increase on a six item scale measure of delinquency. CONCLUSIONS: Infection with T vaginalis was common and significant multivariate predictors comprised a constellation of problem behaviours, each of which are potentially amenable to behavioural intervention.

Adolescent↗

PubMed2002

Production of antigen-specific human monoclonal antibodies: comparison of mice carrying IgH/kappa or IgH/kappa/lambda transloci.

Here we compare human monoclonal antibody (MAb) production from mouse strains that carry disruptions of their endogenous mouse IgH/IgK loci and harbor human IgM + Igkappa(BABkappa) or human IgM + Igkappa + IgA transloci (BABkappa,lambda). We found that whereas both strains proved effective for the isolation of antigen-specific IgM antibodies, many of the IgM MAbs elicited from BABkappa comprise human mu chains that are associated with mouse lambda chains. In contrast, BABkappa,lambda mice gave rise to fully functional, polymeric human IgM antibodies comprising both human IgH and human IgL chains. Therefore, the inclusion of a human Iglambda translocus (in addition to the human IgH + Igkappa transloci) not only diminishes problems of endogenous mouse Iglambda expression but also provides a strain of mice that yields fully human MAbs to a wide range of antigens, as witnessed by the isolation of MAbs to human blood cells, tumor cell lines, and an immunoglobulin idiotype.

Animals↗

PubMed2001

Direct association of Bloom's syndrome gene product with the human mismatch repair protein MLH1.

Bloom's syndrome (BS) is a rare genetic disorder characterised by genomic instability and cancer susceptibility. BLM, the gene mutated in BS, encodes a member of the RecQ family of DNA helicases. Here, we identify hMLH1, which is involved in mismatch repair (MMR) and recombination, as a protein that directly interacts with BLM both in vivo and in vitro, and that the two proteins co-localise to discrete nuclear foci. The interaction between BLM and hMLH1 appears to have been evolutionarily conserved, as Sgs1p, the Saccharomyces cerevisiae homologue of BLM, interacts with yeast Mlh1p. However, cell extracts derived from BS patients show no obvious defects in MMR compared to wild-type- and BLM-complemented BS cell extracts. We conclude that the hMLH1-BLM interaction is not essential for post-replicative MMR, but, more likely, is required for some aspect of genetic recombination.

Adaptor Proteins, Signal Transducing↗

PubMed2001

Potential role for the BLM helicase in recombinational repair via a conserved interaction with RAD51.

Bloom's syndrome (BS) is an autosomal recessive disorder that predisposes individuals to a wide range of cancers. The gene mutated in BS, BLM, encodes a member of the RecQ family of DNA helicases. The precise role played by these enzymes in the cell remains to be determined. However, genome-wide hyper-recombination is a feature of many RecQ helicase-deficient cells. In eukaryotes, a central step in homologous recombination is catalyzed by the RAD51 protein. In response to agents that induce DNA double-strand breaks, RAD51 accumulates in nuclear foci that are thought to correspond to sites of recombinational repair. Here, we report that purified BLM and human RAD51 interact in vitro and in vivo, and that residues in the N- and C-terminal domains of BLM can independently mediate this interaction. Consistent with these observations, BLM localizes to a subset of RAD51 nuclear foci in normal human cells. Moreover, the number of BLM foci and the extent to which BLM and RAD51 foci co-localize increase in response to ionizing radiation. Nevertheless, the formation of RAD51 foci does not require functional BLM. Indeed, in untreated BS cells, an abnormally high proportion of the cells contain RAD51 nuclear foci. Exogenous expression of BLM markedly reduces the fraction of cells containing RAD51 foci. The interaction between BLM and RAD51 appears to have been evolutionarily conserved since the C-terminal domain of Sgs1, the Saccharomyces cerevisiae homologue of BLM, interacts with yeast Rad51. Furthermore, genetic analysis reveals that the SGS1 and RAD51 genes are epistatic indicating that they operate in a common pathway. Potential roles for BLM in the RAD51 recombinational repair pathway are discussed.

Adenosine Triphosphatases↗

PubMed2001

HIV/STD-protective benefits of living with mothers in perceived supportive families: a study of high-risk African American female teens.

BACKGROUND: The joint influence of living with the mother in a perceived supportive family may be an important HIV/STD-protective factor among sexually active female adolescents. METHODS: Sexually active African American female adolescents (N = 522) completed a self-administered survey and structured interview. Adolescents scoring high on family support and reporting that their mother lived with them were compared with the remaining adolescents in respect to unprotected vaginal sex (past 30 days), sex with a non-steady partner (past 6 months), communication with sex partners, attitudes toward condoms, and perceived ability to negotiate condom use. Logistic regression analyses controlled for the influence of parent-adolescent communication about sex and parental monitoring. RESULTS: Adolescents residing with their mothers in a perceived supportive family were more likely to communicate with their sex partners about sexual risk (OR = 1.53). They were less likely to report sex with a non-steady partner (OR = 0.51) or having unprotected sex with a steady partner (OR = 0.52) or any partner (OR = 0.55). CONCLUSIONS: Controlled analyses suggest that living with the mother in a perceived supportive family is an important HIV/STD-protective factor among female adolescents. HIV/STD prevention programs for female adolescents that include the mothers may promote positive and lasting effects.

Adolescent↗

PubMed2001

Correlates of using dual methods for sexually transmitted diseases and pregnancy prevention among high-risk African-American female teens.

PURPOSE: To identify correlates of consistent dual-method use among African-American female adolescents at risk of sexually transmitted diseases (STDs) and pregnancy. METHODS: A convenience sample of 522 sexually active female teens attending adolescent medicine clinics, health department clinics, and school health classes volunteered. Recruitment sites were in low-income neighborhoods of Birmingham, Alabama. Adolescents completed a questionnaire and a face-to-face interview and provided vaginal swab specimens for laboratory diagnosis of STDs. Those reporting use of condoms and at least one other method of contraception, for each of the last five occasions they had sex were classified as consistent dual-method users. The questionnaire assessed frequency of adolescents' communication with their parents and partners about sex. The questionnaire also assessed two measures of parental supervision and adolescents' desire to avoid pregnancy. Multiple logistic regression assessed the independent contribution of each correlate of consistent dual-method use. RESULTS: Seventy-one adolescents (13.6%) were classified as consistent dual-method users. A strong desire to avoid pregnancy was the most influential correlate of consistent dual-method use [odds ratio (OR) =2.3]. Adolescents reporting that their parents generally knew whom they were with (OR = 2.0) and those reporting more frequent communication with parents (OR = 1.9) were also more likely to be consistent dual users. CONCLUSION: The findings suggest the need for research to examine the efficacy of interventions building on adolescent females' desire to avoid pregnancy. Study findings also suggest that interventions promoting improved parent-adolescent communication and improved parental supervision may contribute to adolescents' use of dual methods for STD and pregnancy prevention.

Adolescent↗

PubMed2001

Role of the Bloom's syndrome helicase in maintenance of genome stability.

The RecQ family of DNA helicases has members in all organisms analysed. In humans, defects in three family members are associated with disease conditions: BLM is defective in Bloom's syndrome, WRN in Werner's syndrome and RTS in Rothmund-Thomson syndrome. In each case, cells from affected individuals show inherent genomic instability. The focus of our work is the Bloom's syndrome gene and its product, BLM. Here, we review the latest information concerning the roles of BLM in the maintenance of genome integrity.

Adenosine Triphosphatases↗

PubMed2001

Parent-adolescent communication and sexual risk behaviors among African American adolescent females.

OBJECTIVE: To examine associations between parent-adolescent communication about sex-related topics and the sex-related communication and practices of African American adolescent females with partners, as well as their perceived ability to negotiate safer sex. DESIGN: A theory-guided survey and structured interview were administered to 522 sexually active African American females 14 to 18 years old. Recruitment sites were neighborhoods with high rates of unemployment, substance abuse, violence, and sexually transmitted diseases. Multivariate analyses, controlling for observed covariates, were used to identify the association of less frequent parent-adolescent communication with multiple assessed outcomes. RESULTS: Less frequent parent-adolescent communication (scores below the median) was associated with adolescents' non-use of contraceptives in the past 6 months (adjusted odds ratio [AOR] = 1.7) and non-use of contraceptives during the last 5 sexual encounters (AOR = 1.6). Less communication increased the odds of never using condoms in the past month (AOR = 1.6), during the last 5 sexual encounters (AOR = 1.7), and at last intercourse (AOR = 1.7). Less communication was also associated with less communication between adolescents and their sex partners (AOR = 3.3) and lower self-efficacy to negotiate safer sex (AOR = 1.8). CONCLUSIONS: The findings demonstrate the importance of involving parents in human immunodeficiency virus/sexually transmitted disease and pregnancy prevention efforts directed at female adolescents. Pediatricians and other clinicians can play an important role in facilitating parent-adolescent communication about sexual activity.

Adolescent↗

PubMed2001

Psychosocial correlates of adolescents' worry about STD versus HIV infection: similarities and differences.

BACKGROUND: Adolescents' worry (perceived threat) of sexually transmitted diseases (STDs) and HIV infection may have different correlates. This study examined associations between selected psychosocial and behavioral constructs and adolescents' worry about STD and HIV infection. GOAL: To assess levels and correlates of worry about STD and HIV among a high-risk sample of black adolescent females. STUDY DESIGN: High-risk black females (n = 522), enrolled in a randomized, controlled HIV and STD prevention trial, completed a questionnaire and structured interview at baseline. Worry about STD and HIV infection, recent risk behaviors, and several measures potentially related to worry were assessed. RESULTS: Levels of worry for both STD and HIV were low. Recent history of STD infection was associated with STD worry (OR, 4.6) and HIV worry (OR, 2.0). Infrequent communication about sex (OR, 2.0) and low perceived ability to negotiate condom use (OR, 2.0) were related to STD worry; whereas, only partner-specific barriers were related to HIV worry (OR, 1.9). CONCLUSIONS: Despite high risk, adolescents were generally complacent about the threat of infection with STD and HIV. Adolescents' worry about STD and HIV infection had different sets of correlates.

Adolescent↗

PubMed2001

Socioeconomic status and self-reported gonorrhea among African American female adolescents.

BACKGROUND: Socioeconomic status is often used to explain race differences in sexually transmitted diseases (STDs), yet the independent association of socioeconomic status and STDs among adolescents has been understudied. OBJECTIVE: To examine the associations between socioeconomic status and self-reported gonorrhea among black female adolescents, after controlling for sexual risk behaviors. METHODS: Interviews and surveys were completed by 522 sexually active black adolescent females residing in low-income urban neighborhoods. RESULTS: Adolescents whose parents were unemployed were more than twice as likely to report a history of gonorrhea, compared with those with employed parents. Adolescents living with two parents were less likely to report a history of gonorrhea. CONCLUSIONS: The results of this study indicate that gonorrhea is associated with low socioeconomic status among black adolescent females regardless of the level of sexual risk behaviors. Lower socioeconomic status may be an marker for risky sociosexual environments.

Adolescent↗

PubMed2001

Condom carrying is not associated with condom use and lower prevalence of sexually transmitted diseases among minority adolescent females.

BACKGROUND: Most of the studies associated with condom carrying and use have been conducted with adults. Because minority teenage females are particularly at risk for STD/HIV infection, further investigations specifically focusing on this population are warranted. GOAL: To determine whether observed condom carrying among adolescent females was associated with multiple measures of self-reported condom use, self-reported history of sexually transmitted diseases, and prevalence of biologically confirmed sexually transmitted diseases. METHODS: For this study, 522 sexually active African American adolescent females were recruited from low-income neighborhoods in Birmingham, Alabama. Measures of self-reported condom use, STD history, and condom carrying were collected. Adolescents were also tested for three prevalent sexually transmitted diseases. RESULTS: At the time of the assessment, 8% of the adolescents were observed to have a condom with them. Condom carrying was not found to be significantly associated with condom use and prevalence of sexually transmitted diseases. CONCLUSION: Condom carrying may not be an important outcome of sexually transmitted disease/HIV prevention programs designed to reduce HIV/sexually transmitted disease risk among adolescent females.

Adolescent↗

PubMed2001

Dating violence and the sexual health of black adolescent females.

OBJECTIVE: This study examines the association between having a history of dating violence and the sexual health of adolescent females. METHODS: Black adolescent females (n = 522) completed a survey that assessed dating violence, defined as ever having a physically abusive boyfriend, and an interview that assessed sexual behaviors. RESULTS: Dating violence was reported by 18.4% of adolescents (n = 96). Adolescents with a history of dating violence were, in the past 6 months, 2.8 times more likely to have a sexually transmitted disease, 2.8 times more likely to have nonmonogamous male partners, and half as likely to use condoms consistently. Furthermore, adolescents with a history of dating violence were significantly more likely to fear the perceived consequences of negotiating condom use (odds ratio [OR] = 2.8); fear talking with their partner about pregnancy prevention (OR = 2.6); have a higher perceived risk of acquiring a sexually transmitted disease (OR = 2.1); perceive less control over their sexuality (OR = 2.4); have peer norms nonsupportive of using condoms (OR = 3.1); and have norms nonsupportive of having a healthy relationship (OR = 2.1). CONCLUSIONS: Adolescents who have experienced dating violence are more likely to exhibit a spectrum of unhealthy sexual behaviors, attitudes, beliefs, and norms.

Adolescent↗

PubMed2000

Disruption of mouse polymerase zeta (Rev3) leads to embryonic lethality and impairs blastocyst development in vitro.

Multiple DNA polymerases exist in eukaryotes. Polymerases alpha, delta and epsilon are mainly responsible for chromosomal DNA replication in the nucleus and are required for proliferation. In contrast, the repair polymerases beta and eta are not essential for cellular proliferation in yeast or mice, but a lack of either polymerase can lead, respectively, to defects in base excision repair or the ability to replicate past lesions induced by ultraviolet (UV) radiation [1-3]. Here, we have focused on polymerase zeta. This was first described as a non-essential product of the yeast REV3/REV7 genes involved in UV-induced mutagenesis, and was later implicated in trans-lesion synthesis [4,5]. Unlike in yeast, the mouse homologue (mRev3) was found to be essential for life. Homozygous mutant mice died in utero. Mutant embryos were considerably reduced in size at day 10.5 of development and usually aborted around day 12.5. It is likely that this block reflects a need for mRev3 in proliferative clonal expansion (rather than in the production of a particular cell type) as mutant blastocysts showed greatly diminished expansion of the inner cell mass in culture. Thus, mRev3 could be required to repair a form of externally induced DNA damage that otherwise accumulates during clonal expansion or, consistent with the high homology shared between its Rev7 partner and the mitotic checkpoint gene product Mad2 [6], mRev3 might play a role in cell proliferation and genomic stability even in the absence of environmentally induced damage.

Animals↗

PubMed2000

The Bloom's syndrome gene product interacts with topoisomerase III.

Bloom's syndrome is a rare genetic disorder associated with loss of genomic integrity and a large increase in the incidence of many types of cancer at an early age. The Bloom's syndrome gene product, BLM, belongs to the RecQ family of DNA helicases, which also includes the human Werner's and Rothmund-Thomson syndrome gene products and the Sgs1 protein of Saccharomyces cerevisiae. This family shows strong evolutionary conservation of protein structure and function. Previous studies have shown that Sgs1p interacts both physically and genetically with topoisomerase III. Here, we have investigated whether this interaction has been conserved in human cells. We show that BLM and hTOPO IIIalpha, one of two human topoisomerase III homologues, co-localize in the nucleus of human cells and can be co-immunoprecipitated from human cell extracts. Moreover, the purified BLM and hTOPO IIIalpha proteins are able to bind specifically to each other in vitro, indicating that the interaction is direct. We have mapped two independent domains on BLM that are important for mediating the interaction with hTOPO IIIalpha. Furthermore, through characterizing a genetic interaction between BLM and TOP3 in S. cerevisiae, we have identified a functional role for the hTOPO IIIalpha interaction domains in BLM.

Adenosine Triphosphatases↗

PubMed2000

Children's sexual play and behavior in pre-school settings: staff's perceptions, reports, and responses.

OBJECTIVES: The aims of this study were to learn about the nature, frequency, and patterns of young children's observed sexual play and behavior in pre-school settings, and staff responses to them. METHOD: Fifty eight staff in 11 pre-school settings were interviewed and data obtained about their recall of observed sexualized play and behaviors of children in their care. Responses were sought both to an open question and to 20 different hypothetical scenarios describing children's behaviors with a genital or sexual content. They were asked about the proportion of children observed and the frequency of the behaviors. They were also asked for their predicted responses to encountering each of these scenarios. RESULTS: Children's curiosity about genitalia, looking and limited touching were more commonly observed, and drawing or modeling of genitalia and simulating sexual intercourse were also reported. Children inserting anything into another child and oral-genital contact had only rarely been observed. Rare behaviors always caused concern and led to some intervention. Concern about the more common behaviors was related to additional factors such as frequency, manner and talk accompanying the behavior and to other information known about the child. CONCLUSIONS: The results confirm findings from studies in other countries about the reported prevalence of more and less commonly observed sexual and genitally orientated behaviors in young children. They lend justification for concerns about children showing rarely observed behaviors or showing preoccupation with genitalia and indicate the need for a search for an explanation of these behaviors when observed.

Adult↗

PubMed1998

Physiological regulation of eukaryotic topoisomerase II.

Topoisomerase II is an essential enzyme in all organisms with several independent roles in DNA metabolism. In this article we review our knowledge on the regulation of the expression and catalytic activity of topoisomerase II in both lower and higher eukaryotes. Current data indicate that the regulation of topoisomerase II gene expression is complex, with positive and negative controls in evidence at the level of both promoter activity and mRNA stability. Similarly, the activity of the mature enzyme can be regulated by the action of several different protein kinases. Of particular interest is the cell cycle-dependent phosphorylation of topoisomerase II, including multiple, mitosis-specific modifications, which are proposed to regulate the essential chromosome decatenation activity of the enzyme.

Animals↗

PubMed1998

Targeted gene disruption reveals a role for natural secretory IgM in the maturation of the primary immune response.

Accelerated development of the secondary immune response may be attributable in part to the rapid delivery of antigen to lymphoid follicles by circulating antibody elicited on primary immunization. Here we provide evidence indicating that the nonspecific IgM present in naive mice (natural antibody) plays a role in the acceleration of the primary response. Targeted deletion of the Ig microseconds polyadenylation site by use of Cre recombinase allowed the creation of mice that, although harboring a normal number of B cells expressing surface IgM, completely lacked serum IgM while retaining the other Ig isotypes. These mice retained a broadly normal B lymphocyte distribution (although containing a somewhat expanded peritoneal B1a subset) but exhibited substantial delays in mounting affinity-matured IgG responses to T cell-dependent antigens. The T cell-independent response, however, was augmented. The data indicate that the IgM present before antigen challenge (as well, possibly, as that elicited immediately after immunization) accelerates maturation of the primary response, presumably by complexing with the antigen and facilitating lymphocyte activation and/or antigen trapping.

Animals↗

PubMed1998

Casein kinase II stabilizes the activity of human topoisomerase IIalpha in a phosphorylation-independent manner.

Previous reports have indicated that topoisomerase II (topo II) co-purifies with and is a substrate for casein kinase II. We have carried out a detailed study of the effect that purified casein kinase II has on the activity of purified recombinant human topo IIalpha. Co-incubation of topo IIalpha and casein kinase II led to an apparent activation of the topo IIalpha; however, in experiments in which topo IIalpha was preincubated at 37 degrees C with or without native casein kinase II prior to assaying for decatenation activity, it emerged that the kinase was exerting its "activating" function via a decrease in the rate of topo IIalpha enzyme inactivation during the incubation period. This stabilization of topo IIalpha by casein kinase II was ATP-independent and was observed in both mutated and truncated derivatives of topo IIalpha lacking the major casein kinase II phospho-acceptor sites, indicating the lack of a requirement for phosphorylation. Consistent with a nonenzymatic role for casein kinase II, stoichiometric quantities of kinase were required for topo IIalpha stabilization. These data indicate that casein kinase II plays a significant role in regulating human topo IIalpha protein action via stabilization against thermal inactivation.

Antigens, Neoplasm↗