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Biomedical subjects

S Barnett

Publications and source records attributed to S Barnett.

At least 19 recordsLinked to original sources

Neuronal sodium-channel alpha1-subunit mutations in generalized epilepsy with febrile seizures plus.

Generalized epilepsy with febrile seizures plus (GEFS+) is a familial epilepsy syndrome characterized by the presence of febrile and afebrile seizures. The first gene, GEFS1, was mapped to chromosome 19q and was identified as the sodium-channel beta1-subunit, SCN1B. A second locus on chromosome 2q, GEFS2, was recently identified as the sodium-channel alpha1-subunit, SCN1A. Single-stranded conformation analysis (SSCA) of SCN1A was performed in 53 unrelated index cases to estimate the frequency of mutations in patients with GEFS+. No mutations were found in 17 isolated cases of GEFS+. Three novel SCN1A mutations-D188V, V1353L, and I1656M-were found in 36 familial cases; of the remaining 33 families, 3 had mutations in SCN1B. On the basis of SSCA, the combined frequency of SCN1A and SCN1B mutations in familial cases of GEFS+ was found to be 17%.

Amino Acid Sequence↗

A comparison of vertical force and temporal parameters produced by an in-shoe pressure measuring system and a force platform.

OBJECTIVE: To investigate the ability of Pedar in-shoe system to measure vertical force accurately, by comparing it with the Kistler force platform. DESIGN: In vivo experiment in normal subjects. BACKGROUND: It has been suggested Pedar is highly reliable, but absolute accuracy of the system with regard to force measurement has not been comprehensively tested. METHODS: Sampling at 99 Hz, using five healthy subjects, simultaneous data were collected barefoot, and in three types of shoes (Trainers, Oxfords, Slip-on Deck Type). Six variables obtained from the force/time curve from each footstep were compared. RESULTS: The temporal data recorded by Pedar correlated well with that obtained using Kistler, with significant differences only in overall duration of the step in Deck shoes (P < 0.001) and Oxford shoes (P < 0.01), and peak to peak barefoot (P < 0.01). Pedar recorded a lower first peak force and mid-peak force in all cases (P < 0.001). However, the magnitude of the 2nd peak force recorded by both systems was significantly different only in Trainers (P < 0.05) and Oxford shoes (P < 0.001). The impulse data obtained with Oxford shoes was not significantly different, although barefoot, Trainers and Deck shoes were significantly lower (P < 0.001) for Pedar. CONCLUSIONS: In most cases, comparison of data recorded by the two systems provided good evidence for the accuracy and reliability of temporal measurements and second peak force measurements taken with the Pedar in-shoe system. Relevance. In-shoe pressure data provides evidence for clinical decisions if the systems utilised are proven to be valid, repeatable and accurate. Comparison with an established force platform enables some assessment of these factors.

Adult↗

Induction of potent immune responses by cationic microparticles with adsorbed human immunodeficiency virus DNA vaccines.

The effectiveness of cationic microparticles with adsorbed DNA at inducing immune responses was investigated in mice, guinea pigs, and rhesus macaques. Plasmid DNA vaccines encoding human immunodeficiency virus (HIV) Gag and Env adsorbed onto the surface of cationic poly(lactide-coglycolide) (PLG) microparticles were shown to be substantially more potent than corresponding naked DNA vaccines. In mice immunized with HIV gag DNA, adsorption onto PLG increased CD8(+) T-cell and antibody responses by approximately 100- and approximately 1,000-fold, respectively. In guinea pigs immunized with HIV env DNA adsorbed onto PLG, antibody responses showed a more rapid onset and achieved markedly higher enzyme-linked immunosorbent assay and neutralizing titers than in animals immunized with naked DNA. Further enhancement of antibody responses was observed in animals vaccinated with PLG/DNA microparticles formulated with aluminum phosphate. The magnitude of anti-Env antibody responses induced by PLG/DNA particles was equivalent to that induced by recombinant gp120 protein formulated with a strong adjuvant, MF-59. In guinea pigs immunized with a combination vaccine containing HIV env and HIV gag DNA plasmids on PLG microparticles, substantially superior antibody responses were induced against both components, as measured by onset, duration, and titer. Furthermore, PLG formulation overcame an apparent hyporesponsiveness of the env DNA component in the combination vaccine. Finally, preliminary data in rhesus macaques demonstrated a substantial enhancement of immune responses afforded by PLG/DNA. Therefore, formulation of DNA vaccines by adsorption onto PLG microparticles is a powerful means of increasing vaccine potency.

AIDS Vaccines↗

A multilevel analysis of the effects of rurality and social deprivation on premature limiting long term illness.

STUDY OBJECTIVE: To examine the geographical variation in self perceived morbidity in the south west of England, and assess the associations with rurality and social deprivation. DESIGN: A geographically based cross sectional study using 1991 census data on premature Limiting Long Term Illness (LLTI). The urban-rural and intra-rural variation in standardised premature LLTI ratios is described, and correlation and regression analyses explore how well this is explained by generic deprivation indices. Multilevel Poisson modelling investigates whether Customized Deprivation Profiles (CDPs) and area characteristics improve upon the generic indices. SETTING: Nine counties in the south west of England PARTICIPANTS: The population of the south west enumerated in the 1991 census. MAIN RESULTS: Intra-rural variation is apparent, with higher rates of premature LLTI in remoter areas. Together with high rates in urban areas and lower rates in the semi-rural areas this indicates the existence of a U shaped relation with rurality. The generic deprivation indices have strong positive relations with premature LLTI in urban areas, but these are a lot weaker in semi-rural and rural locations. CDPs improve upon the generic indices, especially in the rural settings. A substantial reduction in unexplained variation in rural areas is seen after controlling for the level of local isolation, with higher isolation, at the wider geographical scale, being related to higher levels of LLTI. CONCLUSIONS: This study highlights the need to treat rural areas as heterogeneous, although this has not been the tendency in health research. Generic deprivation indices are unlikely to be a true reflection of levels of deprivation in rural environments. The importance of CDPs that are specific to the area type and health outcome is emphasised. The significance of physical isolation suggests that accessibility to public and health services may be an important issue, and requires further research.

Adolescent↗

Illegitimate Cre-dependent chromosome rearrangements in transgenic mouse spermatids.

The bacteriophage P1 Cre/loxP system has become a powerful tool for in vivo manipulation of the genomes of transgenic mice. Although in vitro studies have shown that Cre can catalyze recombination between cryptic "pseudo-loxP" sites in mammalian genomes, to date there have been no reports of loxP-site infidelity in transgenic animals. We produced lines of transgenic mice that use the mouse Protamine 1 (Prm1) gene promoter to express Cre recombinase in postmeiotic spermatids. All male founders and all Cre-bearing male descendents of female founders were sterile; females were unaffected. Sperm counts, sperm motility, and sperm morphology were normal, as was the mating behavior of the transgenic males and the production of two-celled embryos after mating. Mice that expressed similar levels of a derivative transgene that carries an inactive Cre exhibited normal male fertility. Analyses of embryos from matings between sterile Cre-expressing males and wild-type females indicated that Cre-catalyzed chromosome rearrangements in the spermatids that lead to abortive pregnancies with 100% penetrance. Similar Cre-mediated, but loxP-independent, genomic alterations may also occur in somatic tissues that express Cre, but, because of the greater difficulty of assessing deleterious effects of somatic mutations, these may go undetected. This study indicates that, following the use of the Cre/loxP site-specific recombination systems in vivo, it is prudent to eliminate or inactivate the Cre recombinase gene as rapidly as possible.

Animals↗

Not such an angel?

Explore the source record for details and available documents.

Journal Article↗

A comparison of vertical force and temporal parameters produced by an in-shoe pressure measuring system and a force platform.

OBJECTIVE: To investigate the ability of Pedar in-shoe system to measure vertical force accurately, by comparing it with the Kistler force platform. DESIGN: In vivo experiment in normal subjects. BACKGROUND: It has been suggested Pedar is highly reliable, but absolute accuracy of the system with regard to force measurement has not been comprehensively tested. METHODS: Sampling at 99 Hz, using five healthy subjects, simultaneous data were collected barefoot, and in three types of shoes (Trainers, Oxfords, Slip-on Deck Type). Six variables obtained from the force/time curve from each footstep were compared. RESULTS: The temporal data recorded by Pedar correlated well with that obtained using Kistler, with significant differences only in overall duration of the step in Deck shoes (P<0. 001) and Oxford shoes (P<0.01), and peak to peak barefoot (P<0.01). Pedar recorded a lower first peak force and mid-peak force in all cases (P<0.001). However, the magnitude of the 2nd peak force recorded by both systems was significantly different only in Trainers (P<0.05) and Oxford shoes (P<0.001). The impulse data obtained with Oxford shoes was not significantly different, although barefoot, Trainers and Deck shoes were significantly lower (P<0.001) for Pedar. CONCLUSIONS: In most cases, comparison of data recorded by the two systems provided good evidence for the accuracy and reliability of temporal measurements and second peak force measurements taken with the Pedar in-shoe system. Relevance In-shoe pressure data provides evidence for clinical decisions if the systems utilised are proven to be valid, repeatable and accurate. Comparison with an established force platform enables some assessment of these factors.

Adult↗

Cancer screening in the elderly population.

This article reviews the current state of knowledge regarding cancer screening in the geriatric population. Care of the elderly requires knowledge of underlying physiologic changes, comorbidities, quality-of-life factors, and life expectancies. There is always the danger that ageism may prevent elderly cancer patients from receiving the proper treatment. On the other hand, overzealous treatment can lead to adverse results if elderly patients are not properly targeted based on current evidence of the benefits and risks of specific screening practices.

Age Factors↗

Characterization of the human glutamate receptor subunit 3 gene (GRIA3), a candidate for bipolar disorder and nonspecific X-linked mental retardation.

The X-chromosome breakpoint in a female patient with a balanced translocation t(X;12)(q24;q15), bipolar affective disorder and mental retardation was mapped within the glutamate receptor 3 (GRIA3) gene by fluorescence in situ hybridization. The GRIA3 cDNA of 5894 bp was cloned, and the gene structure and pattern of expression were determined. The most abundant GRIA3 transcript is composed of 17 exons. An additional 5 exons (2a, 2b, 5a, 5b, and 5c) from the 5' end of the GRIA3 open reading frame were identified by EST analysis (ESTs AI379066 and AA947914). Two new polymorphic microsatellite repeats, (TC)(n=12-26) and (AC)(n=15-19), were identified within GRIA3 5' and 3'UTRs. No mutations were detected in families segregating disorders mapping across GRIA3, one with X-linked bipolar affective disorder (BP) and one with a nonspecific X-linked mental retardation (MRX27). To assess the possibility of the involvement of the GRIA3 gene in familial cases of complex BP, a large set of 373 individuals from 40 pedigrees segregating BP were genotyped using closely linked (DXS1001) and intragenic (DXS1212 and GRIA3 3' UTR (AC)(n))) GRIA3 STR markers. No evidence of linkage was found by parametric Lod score analysis (the highest Lod score was 0. 3 at DXS1212, using the dominant transmission model) or by affected sib-pair analysis.

Adult↗

HIV-1 vaccine-induced immune responses which correlate with protection from SHIV infection: compiled preclinical efficacy data from trials with ten different HIV-1 vaccine candidates.

The specific immune mechanisms necessary and/or sufficient to elicit HIV-vaccine protection remain undefined. Utilising the SHIV rhesus macaque model the immunogenicity as well as the efficacy of ten different HIV-1 vaccine candidates was evaluated. Comparison of the immune responses induced, with the ability of the vaccine to protect from SHIV infection provided a means to determine which type of immune responses were necessary for protection. Vaccine candidates included VLPs, DNA, subunit protein with novel adjuvant formulations, ISCOMs and pox-virus vectors. Protection from SHIV infection was achieved in approximately half of the animals which received a primary intravenous cell-free challenge. The presence of CTL in the absence of other effector responses did not correlate with protection from this route and type of challenge. Virus neutralising antibodies (Nab) appeared to be necessary but alone were insufficient for protection. If Ag-specific IFN-gamma and/or IL-4 as well as lymphoproliferative (LP) responses were found with the lack of a detectable IL-2 response, then protection was not observed. Immunity correlated with the magnitude of Nab responses, beta-chemokines and as well as balanced, qualitative T-helper responses.

AIDS Vaccines↗

Cross-subtype neutralizing antibodies induced in baboons by a subtype E gp120 immunogen based on an R5 primary human immunodeficiency virus type 1 envelope.

Global human immunodeficiency virus type 1 (HIV-1) diversity may require engineering vaccines to express antigens representing strains prevalent in the target population of vaccine testing. The majority (90%) of incident infections in Thailand are genetic subtype E, with a small percentage of subtype B infections in the intravenous drug user populations. We have evaluated and compared the binding and HIV-1 neutralizing properties of serum antibodies induced in baboons by CHO cell-expressed monomeric gp120 derived from a CCR5-using (R5) subtype E primary HIV-1CM235 or a CXCR4-using (X4) subtype B T-cell line-adapted (TCLA) HIV-1SF2 isolate. In contrast to the subtype-specific HIV-1 neutralizing antibodies induced with recombinant HIV-1SF2 gp120 (rgp120SF2), rgp120CM235 immunization induced antibodies capable of neutralizing both subtype E and subtype B TCLA HIV-1 isolates. However, neither immunogen induced antibodies capable of neutralizing primary HIV-1 isolates. Antibody induced by rgp120CM235 preferentially bound natively folded gp120 and retained strong cross-reactivity against multiple gp120 strains within subtype E as well as subtype B. In contrast, antibody responses to rgp120SF2 were directed predominantly to linear epitopes poorly exposed on native gp120 and had more limited cross-recognition of divergent gp120. Fine epitope mapping revealed differences in antibody specificities. While both rgp120CM235 and rgp120SF2 induced antibodies to regions within C1, V1/V2, V3, and C5, unique responses were induced by rgp120CM235 to multiple epitopes within C2 and by rgp120SF2 to multiple epitopes within C3, V4, and C4. These data demonstrate that strain and/or phenotypic differences of HIV-1 subunit gp120 immunogens can substantially alter antibody binding specificities and subsequent HIV-1 neutralizing capacity.

AIDS Vaccines↗

Smoking and deaf adults: associations with age at onset of deafness.

Smoking is a major health problem whose prevalence in different populations is thought to be influenced by sociocultural and linguistic factors. Although smoking and hearing loss are positively correlated, little is known about the smoking habits of deaf populations. Using national survey data, this study determined the smoking prevalence in two socioculturally distinct deaf populations, based on age at onset of deafness. The smoking prevalence in each deaf population was compared to the smoking prevalence in the hearing population in multivariate analyses that adjusted for sociodemographics and health status. The smoking prevalence among postlingually deafened adults was not significantly different from that among hearing adults. Prelingually deafened adults were found to be less likely to smoke than hearing adults, even though they have less education and lower income, factors both associated with higher smoking prevalence in other populations. The lower smoking prevalence among prelingually deafened adults may be due to cultural differences or to limited access to English-language tobacco advertising.

Adult↗

Pediatricians' response to the demand for school health programming.

OBJECTIVE: Because of the broad and increasing interest in school health, the American Academy of Pediatrics (AAP) surveyed its members to determine their awareness of school health education/programs, their level of participation, their desire to participate, and their resource needs to participate more effectively. METHODS: Self-administered questionnaires were mailed to a randomized representative sample of AAP members (N = 1602). Overall response rate was 64.5%. Some responses were stratified for analysis by gender; age (>45 years or </=45 years); practice area (urban, suburban, or rural); practice setting (solo, group, or hospital); and type of practice (general versus specialty). chi2 Tests were used to compare responses. RESULTS: Greater than half of the pediatricians who responded to the questionnaire were aware of school health education curriculum on risky adolescent behaviors in their community, counseling services (58%), school nursing services (63%), and screening services (71%); however, more than half were not aware of curriculum on injury/violence prevention, fitness, or whether a school health advisory council was available. Most pediatricians supported comprehensive school health education (pregnancy prevention, 82%; violence prevention, 77%; mental health, 56%). Also, respondents supported services (counseling, 76%; nutrition, 65%; screening/referral, 58%; school-based primary care, 58%). Although 22% of AAP pediatricians are currently working with local school programs, >70% wanted to become involved or more involved and needed information on how they may be able to participate. Only 25% believed they were adequately prepared. Two thirds believed school-based clinics were one of the best ways to reach underserved children and adolescents and should include preteens. CONCLUSION: AAP pediatricians want to become more involved with comprehensive school health programs. The ways in which they want to participate vary substantially. Most pediatricians thought they needed additional education. The AAP has developed recommendations for graduate medical education and continuing medical education for pediatricians to participate in integrated school health services.

Attitude of Health Personnel↗

Telephone ownership and deaf people: implications for telephone surveys.

OBJECTIVES: This study was done to determine the prevalence of telephone ownership in different deaf populations and to explore its implications for telephone-based surveys. METHODS: Multivariate analyses, with adjustments for sociodemographics and health status, were done of National Health Interview Survey (NHIS) data from 1990 and 1991, the years in which the NHIS Hearing Supplement was administered. RESULTS: Prelingually deafened adults were less likely than members of the general population to own a telephone (adjusted odds ratio [AOR] = 0.35; 95% confidence interval [CI] = 0.15, 0.82), whereas postlingually deafened adults were as likely as members of the general population to own one (AOR = 1.00; 95% CI = 0.78, 1.28). CONCLUSIONS: Telephone surveys risk marginalizing prelingually deafened adults because of low telephone ownership and language barriers between the deaf and hearing communities.

Adult↗

Experimental test of harmonic contribution to the thermal index for soft tissue.

Experimental data were gathered for the heating effect of an ultrasound beam propagating in water and incident on a thermal test object containing artificial tissue in which a fine-wire thermocouple was embedded close to the beam entrance. The extent of temperature elevations in the artificial tissue was limited by using a constant low value for spatial peak temporal average ultrasound intensity so that the medium did not denature. The adjusted (for continuous wave conditions) maximum temperatures reached in a fixed exposure time initially increased linearly with increase in the spatial peak pulse average ultrasound intensity, but, for the higher values of this parameter, exceeded that expected from a linear relationship. In addition to the fundamental frequency, significant higher frequencies were present in the beam at high intensities, which caused additional enhancement of the ultrasound heating. Calculations of W(DEG) for evaluation of the thermal index should include the evaluation of the heating contributions from all frequencies present in the beam.

Agar↗