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Biomedical subjects

L Bennett

Publications and source records attributed to L Bennett.

At least 19 recordsLinked to original sources
PubMed2001

MAPS: a microarray project system for gene expression experiment information and data validation.

SUMMARY: MAPS is a MicroArray Project System for management and interpretation of microarray gene expression experiment information and data. Microarray project information is organized to track experiments and results that are: (1) validated by performing analysis on stored replicate gene expression data; and (2) queried according to the biological classifications of genes deposited on microarray chips.

Computer Communication Networks↗
PubMed2000

The prevalence of a history of child sexual abuse among adults visiting family practitioners in Israel.

OBJECTIVE: To determine the prevalence of a history of child sexual abuse (CSA) in a random sample of adult patients presenting for routine health care to family practice clinics in Israel. METHOD: One thousand and five randomly selected patients aged 18 to 55, attending 48 clinics, participated in this questionnaire study. RESULTS: Twenty-five percent indicated that they had been sexually abused as children. More women reported CSA (p < .0001 ) than men, as did women originating from Western countries (p = .02) and those with more than 12 years of education (p = .01). There were no significant associations between CSA and the other socio-demographic variables examined. Fondling was the most common and intercourse the least common activity experienced. Forty-five percent of the perpetrators were previously known. The mean age at which the child sexual abuse began varied between 10 and 14. Only 45% of the subjects had ever told anyone about the experience. CONCLUSIONS: Since no other prevalence study has been reported to date in Israel, these findings suggest that as in other Western countries CSA is a relatively common problem. Family physicians and other health professionals should be aware of this high prevalence and its known potential for initial and long-term deleterious outcomes.

Adolescent↗
PubMed2000

Predicting human oral bioavailability of a compound: development of a novel quantitative structure-bioavailability relationship.

PURPOSE: The purpose of this investigation was to develop a quantitative structure-bioavailability relationship (QSBR) model for drug discovery and development. METHODS: A database of drugs with human oral bioavailability was assembled in electronic form with structure in SMILES format. Using that database, a stepwise regression procedure was used to link oral bioavailability in humans and substructural fragments in drugs. The regression model was compared with Lipinski's Rule of Five. RESULTS: The human oral bioavailability database contains 591 compounds. A regression model employing 85 descriptors was built to predict the human oral bioavailability of a compound based on its molecular structure. Compared to Lipinski's Rule of Five, the false negative predictions were reduced from 5% to 3% while the false positive predictions decreased from 78% to 53%. A set of substructural descriptors was identified to show which fragments tend to increase/decrease human oral bioavailability. CONCLUSIONS: A novel quantitative structure-bioavailability relationship (QSBR) was developed. Despite a large degree of experimental error, the model was reasonably predictive and stood up to cross-validation. When compared to Lipinski's Rule of Five, the QSBR model was able to reduce false positive predictions.

Administration, Oral↗
PubMed2000

Mutational and haplotype analyses of families with familial partial lipodystrophy (Dunnigan variety) reveal recurrent missense mutations in the globular C-terminal domain of lamin A/C.

Familial partial lipodystrophy (FPLD), Dunnigan variety, is an autosomal dominant disorder characterized by marked loss of subcutaneous adipose tissue from the extremities and trunk but by excess fat deposition in the head and neck. The disease is frequently associated with profound insulin resistance, dyslipidemia, and diabetes. We have localized a gene for FPLD to chromosome 1q21-q23, and it has recently been proposed that nuclear lamin A/C is altered in FPLD, on the basis of a novel missense mutation (R482Q) in five Canadian probands. This gene had previously been shown to be altered in autosomal dominant Emery-Dreifuss muscular dystrophy (EDMD-AD) and in dilated cardiomyopathy and conduction-system disease. We examined 15 families with FPLD for mutations in lamin A/C. Five families harbored the R482Q alteration that segregated with the disease phenotype. Seven families harbored an R482W alteration, and one family harbored a G465D alteration. All these mutations lie within exon 8 of the lamin A/C gene-an exon that has also been shown to harbor different missense mutations that are responsible for EDMD-AD. Mutations could not be detected in lamin A/C in one FPLD family in which there was linkage to chromosome 1q21-q23. One family with atypical FPLD harbored an R582H alteration in exon 11 of lamin A. This exon does not comprise part of the lamin C coding region. All mutations in FPLD affect the globular C-terminal domain of the lamin A/C protein. In contrast, mutations responsible for dilated cardiomyopathy and conduction-system disease are observed in the rod domain of the protein. The FPLD mutations R482Q and R482W occurred on different haplotypes, indicating that they are likely to have arisen more than once.

Alleles↗
PubMed2000

Human population expansion and microsatellite variation.

Polymorphisms at di-, tri-, and tetranucleotide microsatellite loci have been analyzed in 14 worldwide populations. A statistical index of population expansion, denoted S(k), is introduced to detect historical changes in population size using the variation at the microsatellites. The index takes the value 0 at equilibrium with constant population size and is positive or negative according to whether the population is expanding or contracting, respectively. The use of S(k) requires estimation of properties of the mutation distribution for which we use both family data of Dib et al. for dinucleotide loci and our population data on tri- and tetranucleotide loci. Statistical estimates of the expansion index, as well as their confidence intervals from bootstrap resampling, are provided. In addition, a dynamical analysis of S(k) is presented under various assumptions on population growth or decline. The studied populations are classified as having high, intermediate, or low values of S(k) and genetic variation, and we use these to interpret the data in terms of possible population dynamics. Observed values of S(k) for samples of di-, tri-, and tetranucleotide data are compatible with population expansion earlier than 60,000 years ago in Africa, Asia, and Europe if the initial population size before the expansion was on the order of 500. Larger initial population sizes force the lower bound for the time since expansion to be much earlier. We find it unlikely that bottlenecks occurred in Central African, East Asian, or European populations, and the estimated expansion times are rather similar for all of these populations. This analysis presented here suggests that modern human populations departed from Africa long before they began to expand in size. Subsequently, the major groups (the African, East Asian, and European groups) started to grow at approximately same time. Populations of South America and Oceania show almost no growth. The Mbuti population from Zaire appears to have experienced a bottleneck during its expansion.

Animals↗
PubMed1999

The association of the combination of sumatriptan and methysergide in myocardial infarction in a premenopausal woman.

Acute myocardial infarction occurred in a 43 year-old premenopausal woman with controlled hypertension and no known coronary artery disease following the use of the antimigraine medications sumatriptan succinate injectable form and methysergide maleate. The use of sumatriptan is contraindicated within 24 hours of using ergotamine or ergotamine-type medications such as methysergide. This contraindication is based on the theoretical possibility of prolonged vasospasm with the combined use. Methysergide is primarily a serotonin type 2 (5-HT2) antagonist, although it does act as a partial agonist at 5-HT1 receptors. It is believed that a major component of coronary artery vasospasm is possibly due to 5-HT supersensitivity mediated by 5-HT1Dbeta receptor activation. Drugs that selectively stimulate the 5-HT(D) receptors, such as sumatriptan, are potentially hazardous in people with underlying coronary artery disease, and agents with additional agonistic properties at these receptors may potentiate this effect. Physicians should be warned to inquire about prior 24-hour medication use before prescribing antimigraine medication.

Adult↗
PubMed1999

Predictors of dropout and burnout in AIDS volunteers: a longitudinal study.

Burnout among HIV/AIDS volunteers contributes to the loss of dedicated personnel resulting in strain on the HIV/AIDS care system. Past research has suggested that there were significant stresses and burnout associated with AIDS caregiving. We investigated the predictors of dropout in AIDS volunteers over time, and specifically, which of the variables of the stressors and rewards of being a volunteer (collected at baseline) predicted who would drop out two years later. The volunteers were the subjects of Nesbitt et al. (1996), who were members of an interfaith religious-based organization in Houston, Texas. The subjects were re-contacted by mail after two years, and 76 of the 174 respondents completed a brief questionnaire which gave details of current volunteering activity, reasons for dropout (if they had dropped out) and completed the Texas Revised Inventory of Grief (TRIG). Forty dropped-out from volunteering while 36 continued. Data show the independent variables of total stressor score, the Maslach Burnout Inventory score of Depersonalization intensity and the three subscale scores involving stress: client problems and role ambiguity, emotional overload and organizational factors as being significant in predicting dropout in HIV/AIDS volunteers over time. The best predictors of the dropping-out of HIV/AIDS volunteers can be divided into the stresses (client problems and role ambiguity, emotional overload and organizational factors) and depersonalization intensity. The results showed that volunteers who experienced more client problems and role ambiguity, more emotional overload and more problems with organizational factors are more likely to drop out from the volunteer programme. They also show that the dropout volunteers have a significantly higher level of depersonalization intensity than the continuing volunteers, with the risk of dropout increasing by almost a third in the highest tertile of depersonalization intensity scores compared with those with lower scores. These data indicate that it is the stressors of AIDS volunteering, including the intensity of depersonalization, which lead to dropout, and that rewards do not appear to have a protective effect.

Acquired Immunodeficiency Syndrome↗
PubMed1999

A high-resolution physical map of human chromosome 21p using yeast artificial chromosomes.

The short arm of human chromosome 21 (21p) contains many different types of repetitive sequences and is highly homologous to the short arms of other acrocentric chromosomes. Owing to its repetitive nature and the lack of chromosome 21p-specific molecular markers, most physical maps of chromosome 21 exclude this region. We constructed a physical map of chromosome 21p using sequence tagged site (STS) content mapping of yeast artificial chromosomes (YACs). To this end, 39 STSs located on the short arm or near the centromere of chromosome 21 were constructed, including four polymorphic simple tandem repeats (STRs) and two expressed sequence tags (ESTs). Thirty YACs were selected from the St. Louis YAC library, the chromosome 21-enriched ICRF YAC library, and the CEPH YAC and megaYAC libraries. These were assembled in a YAC contig map ranging from the centromere to the rDNA gene cluster at 21p12. The total size of the region covered by YACs is estimated between 2.9 and 5 Mb. The integrity of the YAC contig was confirmed by restriction enzyme fingerprinting and fluorescence in situ hybridization (FISH). One gap with an estimated size of 400 kb remained near the telomeric end of the contig. This YAC contig map of the short arm of human chromosome 21 constitutes a basic framework for further structural and functional studies of chromosome 21p.

Chromosomes, Artificial, Yeast↗
PubMed1999

Variation in the arousal pattern after obstructive events in obstructive sleep apnea.

The relationship between the severity of obstructive sleep apnea (OSA) (measured by sleep study) and daytime sleepiness is poor. Variation in the degree of arousal accompanying obstructive respiratory events might help explain this poor correlation. Polysomnographic records from patients with OSA were reviewed in order to extract representative examples of apneas and hypopneas (in 10 patients), as well as events both supine and decubitus (in 12 patients). The EEG accompanying each obstructive event was processed with a neural network technique to describe sleep depth on a second-by-second basis. The lengths of any visually evident microarousals were also measured manually. There was considerable interindividual variation in the degree of sleep disturbance using the neural network technique (p < 0.005), but not using the lengths of the visually scored microarousals (p = 0.6). The arousals accompanying apneic events caused greater variability in sleep depth quantified using the neural network technique (p = 0.03), and also lasted longer based on the visual scoring (mean, 12.6; SD, 1.7 s) than the hypopneic events (mean, 9.9; SD, 2.4 s; p = 0.02). There were no significant differences between events occurring supine versus decubitus with either technique (p = 0.7). These differences in arousal magnitude may explain some of the poor correlations between conventional measures of sleep apnea severity and daytime sleepiness.

Arousal↗
PubMed1999

Children's needs in shelters: mother's perceptions.

The needs of children who witness violence directed at their mothers have only recently gained attention. While shelter services to address children's responses are increasingly evident, there is still much we do not understand about their plight, particularly from the perspective of their mothers. This study used focus-group methodology to identify mothers' perceptions of their children's needs while they were in shelters. Five focus group sessions were held with 27 mothers who had experienced violence in their homes and had used shelter services within the previous two-year period. Data were analyzed to identify six dominant categories of need and 12 supporting thematic categories. The dominant categories included: the counselling needs of the children; day-to-day living needs, such as maintaining family integrity and normality; recreational needs; the needs of children with respect to parenting; and finally, aspects of shelter support for mothers, and the impact of the shelter environment on children. The implications of the findings for program development are discussed.

Adult↗
PubMed1999

Court-involved battered women's responses to violence: the role of psychological, physical, and sexual abuse.

Failure to understand the importance of psychological abuse as a component of domestic violence can result in little appreciation for the complexity of victims' experience and thus a failure to provide the most effective intervention. This study examined the role of psychological abuse, physical violence, injury, and sexual abuse in predicting court-involved women's (1) prior attempts to seek help from the justice system and to leave the battering relationship, (2) use of criminal prosecution and civil protection orders, and (3) traumatic stress reactions. At the univariate level, each abuse variable was significantly associated with at least one strategic response and all traumatic responses to violence. Multivariate analyses revealed that strategic responses were largely predicted by injury and physical assault, whereas traumatic responses were mainly predicted by psychological abuse. Taken together, these findings demonstrate the important role of both physical and psychological abuse in shaping women's responses to domestic violence.

Adaptation, Psychological↗
PubMed1999

Obstacles to victims' cooperation with the criminal prosecution of their abusers: the role of social support.

Over the last 20 years, diminishing tolerance for domestic violence has triggered significant criminal justice reforms designed to facilitate the prosecution of abusers. Prosecutors, for example, have adopted policies requiring that cases go forward even if the victim later has second thoughts. Although increasingly common, these "no drop" policies reflect a profound irony about domestic cases that is well known but little understood: the most formidable problem in prosecuting such cases is often the victim's own unwillingness to bring the abuser to justice. This prospective study explored a range of factors potentially predictive of domestic violence victims' cooperation with the prosecution of their abusers. Although the study focused on interpersonal and institutional social support, it also investigated the influence of violence severity, victim demographic factors, and victim mental health characteristics, including the presence of depressive symptoms, emotional dependence on the abuser, and substance abuse. Findings showed that tangible support, severity of violence in the relationship, and the presence of children in common with the abuser all significantly predicted victims' cooperation with the prosecution of their abusers. Substance abuse significantly predicted victims' noncooperation with prosecution. The research and policy implications of these findings are discussed.

Adolescent↗
PubMed1998

Altered cell surface expression and signaling of leptin receptors containing the fatty mutation.

Leptin and the leptin receptor are key players in the regulation of body weight. In an attempt to dissect the molecular mechanism of the Zucker fatty rat leptin receptor mutation (Gln269 --> Pro) we analyzed the effects of this mutation on leptin receptor signaling and expression in three different expression systems: 1) 32D cells expressing leptin/erythropoietin receptor chimeras, 2) COS-7 cells expressing a leptin receptor short form, and 3) 293 cells expressing soluble receptor forms. To determine if the Gln269 --> Pro mutation is critical for the observed phenotype, we made a similar Gln --> Pro mutation at a vicinal residue two amino acids upstream of the fatty mutation to see if it would have similar effects. Incorporation of either of the Gln --> Pro mutations into wild type receptor forms did not interfere with leptin binding, but it resulted in a signaling-incompetent receptor. In addition, the majority of the mutant receptor protein was localized intracellularly. Our results suggest that the obese phenotype resulting from the Gln269 --> Pro mutation in the leptin receptor of the Zucker fatty rat may be due not only to a reduced cell surface expression of this form of the leptin receptor, but also to a post-leptin binding malfunction of the receptor that interferes with subsequent signal transduction.

Animals↗
PubMed1998

Sexual and severe physical violence among high school students. Power beliefs, gender, and relationship.

In a sample of 463 high school students, 43% reported being the victim of either sexual violence or severe physical violence by peers in the past year. Perpetrators were more likely to be known rather than unknown to the victim, or to be dating/ex-dating partners, and 70% of those who experienced violence by peers were girls. Findings support a view of high school peer violence that encompasses relationship, gender, effects on the victim, and beliefs about both male role power and personal power.

Adolescent↗
PubMed1998

Localization of the gene for familial partial lipodystrophy (Dunnigan variety) to chromosome 1q21-22.

Obesity is strongly implicated in the pathophysiology of insulin resistance, diabetes mellitus and dyslipidemia. The mechanisms, however, by which obesity causes these complications are not known. The study of single-gene disorders affecting adipose tissue may elucidate some of the mechanisms involved in these processes. Familial partial lipodystrophy, Dunnigan variety, (FPLD, OMIM 308980) is an autosomal-dominant condition characterized by marked loss of subcutaneous adipose tissue affecting the trunk and extremities but with excess fat deposition in the head and neck areas. Affected individuals show an increased preponderance of insulin resistance, diabetes mellitus, dyslipidemia and acanthosis nigricans. The genetic basis of FPLD is unknown. We carried out a genome-wide scan with a set of highly polymorphic short tandem-repeats (STR) in individuals from five well-characterized pedigrees and mapped the FPLD locus to chromosome 1q21-22. The maximum two-point lod score obtained with a highly polymorphic microsatellite at D1S2624 at theta(max)=0 was 5.84. Multipoint-linkage analysis yielded a peak lod score of 8.25 between D1S305 and D1S1600. There was no evidence for genetic heterogeneity (alpha=1) in the pedigrees.

Chromosomes, Human, Pair 1↗
PubMed1998

Psychological and socio-medical aspects of HIV/AIDS: a reflection on publications in AIDS care (1989-1995).

It is necessary to consider the content and methods of AIDS social research publications for these represent research advances as well as current issues of concern for practitioners, communities and researchers alike. This article critically examines some of the research that has been conducted to date into social aspects of HIV and AIDS. It quantifies the content and major methodological style of publications in the journal AIDS Care from 1989 to 1995. The most commonly published topic area in AIDS Care, during this period was cultural and demographic issues (15.9%), followed by issues pertinent to the psychological impact of HIV (13.6%), sexual behaviour and condom use (11.3%) and policy and services (9.5%). Research and measurement issues were the least examined content area in AIDS Care 1989-1995 (2.6%). This article discusses possible variables that influence the style and topics that are published in AIDS Care and makes suggestions for authors to consider before embarking on future research projects or publications.

Acquired Immunodeficiency Syndrome↗