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Biomedical subjects

M Bell

Publications and source records attributed to M Bell.

At least 55 records · Page 3Linked to original sources

Assessment of abdominal fat development in young adolescents using magnetic resonance imaging.

OBJECTIVE: To determine the patterns of change and the best anthropometric indicators of intra-abdominal fat deposition in young adolescents from ages 11-13 y. SUBJECTS: Subjects were 25 boys (mean age 13.7 +/- 0.32 y) and 17 girls (mean age of 13.7 +/- 0.23 y) who had taken part in a similar study 2 y earlier at ages 11.5 +/- 0.33 y and 11.5 +/- 0.27 y, respectively. METHODS: Intra-abdominal (IA) and subcutaneous adipose (SA) tissue areas and IA/SA ratio were determined through four tranverse magnetic resonance imaging scans on two occasions. Differences were investigated using t-tests and ANOVA. Skinfolds, girths and circumferences, body mass index and hydrostatic weighing were also recorded. Pearson correlation coefficients and regression equations were calculated to determine the best anthropometric indicators of intra-abdominal fat deposition. RESULTS: Intra-abdominal fat and subcutaneous fat areas had significantly increased in boys and girls by the second measure. Boys had deposited greater amounts of fat in intra-abdominal depots so that their intra-abdominal/subcutaneous ratio had increased significantly from 0.31 to 0.39. This had reduced in girls from 0.39 to 0.35. However, patterns of change were variable within sexes. Truncal skinfold sites (r = 0.54-0.70) emerged as the best field indicators of intra-abdominal fat deposition. CONCLUSIONS: Patterns of intra-abdominal and subcutaneous fat distribution are identifiable in pubescent children using magnetic resonance imaging. An acceptable indication is provided by truncal skinfolds.

Abdomen↗

Acceptability of baseball face guards and reduction of oculofacial injury in receptive youth league players.

GOALS: To assess the relative injury reduction effect and acceptability of face guards on batter's helmets. METHODS: A non-randomized prospective cohort study among 238 youth league baseball teams in Central and Southern Indiana during the 1997 season. Coaches, parents, and players were asked to respond to pre-season and post-season questionnaires. Approximately one half of the teams were supplied with face guard helmets (intervention); all others used this protection at their discretion (comparison). RESULTS: Parents, players, and coaches on the intervention teams reported a reduction in the incidence of oculofacial injuries compared with comparison team respondents (p=0.04). There was no reported adverse effect of face guard use on player performance. CONCLUSIONS: Helmet face guards should be required for batters to prevent facial injuries in baseball.

Attitude to Health↗

Local road traffic activity and the prevalence, severity, and persistence of wheeze in school children: combined cross sectional and longitudinal study.

OBJECTIVES: To investigate the relation between local road traffic activity and the occurrence, severity, and persistence of wheeze in children. METHODS: Data on wheeze and asthma were collected in a cross sectional questionnaire survey of 22,968 primary school children (age 4-11) and 27,826 secondary school children (age 11-16) in the Nottingham area. Direct measures of road traffic flow were made in the locality of each school and combined with Local Authority traffic data for major roads to estimate local traffic activity in vehicle metres/day/km2. Assessment of the effects of potential confounders was performed in nested case-control groups of 6576 primary and 5936 secondary children. Data on frequency of wheeze were collected for the cases to study disease severity. Longitudinal data on a historical cohort of 883 children who reported wheeze when aged 4-11 in 1988 were used to study the persistence of wheeze into adolescence. RESULTS: Unadjusted prevalence of wheeze in the past year within schools varied widely but was not associated with traffic activity in the school locality (weighted regression coefficient beta = -0.01, p = 0.93 for primary schools, beta = -0.18, p = 0.26 for secondary schools). The risk of wheeze in individual primary school children was not associated with traffic activity analysed as a continuous variable, although there was some suggestion of a weak, non-linear plateau effect. Similar effects were found for diagnosed asthma and recent cough. There was no evidence of any relation between traffic activity and risk of wheeze in secondary school children. There were positive but non-significant dose related effects of traffic activity on wheeze severity in primary and secondary children and on persistence of wheeze in the longitudinal cohort. CONCLUSIONS: Traffic activity in the school locality is not a major determinant of wheeze in children.

Adolescent↗

Reactions to prenatal testing: reflection of religiosity and attitudes toward abortion and people with disabilities.

To better understand factors associated with prenatal testing decisions, we asked individuals what they would do if through prenatal testing they discovered that they (or their partner) were carrying an affected fetus. Respondents were more uncertain about whether to continue the pregnancy when the fetus was diagnosed as having Down syndrome than when the fetus had spina bifida or hemophilia and less certain about continuing a fetus with spina bifida than one with hemophilia. There was modest support for the hypothesis that negative attitudes toward people with disabilities would be associated with an increased likelihood of choosing abortion. Religious affiliation was associated only with the decision concerning the fetus with hemophilia; church attendance was associated with the decisions concerning fetuses with all three diagnoses.

Abortion, Eugenic↗

Adherence to antiviral drug regimens in HIV-infected adolescent patients engaged in care in a comprehensive adolescent and young adult clinic.

Inconsistent use of antiviral medications for the treatment of HIV may lead to the emergence of resistant strains in HIV-infected adults. Patterns of adherence with these drug regimens in adolescents remains unknown. Identifying nonadherence in HIV-infected patients to antiviral regimens and developing corrective measures could improve patient outcomes. This study was undertaken to understand adherence in HIV-infected youths engaged in care and to reduce patterns of nonadherence. A retrospective analysis of 25 charts (78%) of HIV-infected youths (n = 32, age 13 to 21 years) were consecutively reviewed from January 1993 to May 1998. Charts were reviewed for documentation of factors previously documented to be associated with adherence: housing stability, social support, prior sexually transmitted diseases (STDs) and/or pregnancy, HIV exposure category, number of clinic visits, number of pills per day, number of medications per day, knowledge of medication schedule, age, gender, race/ethnicity, health status as revealed by CD4 count and viral load, and recorded patterns of adherence to medications and clinic appointments. Thirteen of the 18 (72%) patients who were receiving antiretroviral medication were nonadherent. Sixty-seven percent of the females and 80% of the males reported missing doses. Housing instability (p = 0.031) and/or length of treatment with antiviral medications (months of treatment) (p = 0.043) were significantly correlated with nonadherence. The stability of the adolescents' living situations was the most significant correlate of medication adherence for this population of HIV-infected youth.

Adolescent↗

Functioning of the Drosophila integral U1/U2 protein Snf independent of U1 and U2 small nuclear ribonucleoprotein particles is revealed by snf(+) gene dose effects.

Snf, encoded by sans fille, is the Drosophila homolog of mammalian U1A and U2B" and is an integral component of U1 and U2 small nuclear ribonucleoprotein particles (snRNPs). Surprisingly, changes in the level of this housekeeping protein can specifically affect autoregulatory activity of the RNA-binding protein Sex-lethal (Sxl) in an action that we infer must be physically separate from Snf's functioning within snRNPs. Sxl is a master switch gene that controls its own pre-mRNA splicing as well as splicing for subordinate switch genes that regulate sex determination and dosage compensation. Exploiting an unusual new set of mutant Sxl alleles in an in vivo assay, we show that Snf is rate-limiting for Sxl autoregulation when Sxl levels are low. In such situations, increasing either maternal or zygotic snf(+) dose enhances the positive autoregulatory activity of Sxl for Sxl somatic pre-mRNA splicing without affecting Sxl activities toward its other RNA targets. In contrast, increasing the dose of genes encoding either the integral U1 snRNP protein U1-70k, or the integral U2 snRNP protein SF3a(60), has no effect. Increased snf(+) enhances Sxl autoregulation even when U1-70k and SF3a(60) are reduced by mutation to levels that, in the case of SF3a(60), demonstrably interfere with Sxl autoregulation. The observation that increased snf(+) does not suppress other phenotypes associated with mutations that reduce U1-70k or SF3a(60) is additional evidence that snf(+) dose effects are not caused by increased snRNP levels. Mammalian U1A protein, like Snf, has a snRNP-independent function.

Alleles↗

A full-length Cbfa1 gene product perturbs T-cell development and promotes lymphomagenesis in synergy with myc.

The Cbfa1/PEBP2 alpha A/AML3 gene plays an essential role in osteogenesis but is also expressed in the T-cell lineage where it has been implicated in lymphoma development as a target for retroviral insertional mutagenesis. As lymphoma cells with til-1 insertion express at least five distinct Cbfa1 isoforms, it is important to establish which, if any, have intrinsic oncogenic potential. We have generated transgenic mice in which the most abundant lymphoma isoform (G1/p57) is expressed under the control of the CD2 locus control region. Co-precipitation analysis of transgenic thymus revealed high levels of Cbfa1 protein in an abundant complex containing the binding cofactor Cbfb. CD2-Cbfa1-G1 mice displayed abnormal T-cell development, with a pronounced skew towards CD8 SP cells in the thymus and developed a low incidence of spontaneous lymphomas (6% at 12 months) with cells of similar phenotype. Strongly synergistic tumour development was seen when CD2-Cbfa1-G1 mice were crossed with lines carrying myc transgenes (CD2-myc or tamoxifen-regulatable CD2-mycER) and Cbfa1 was found to rescue expression of the CD2-myc transgene in pre-leukaemic mice. However, synergy did not appear to be due to a dominant block of myc-induced apoptosis by Cbfa1 as explanted primary tumours and cell lines from CD2-Cbfa1-G1/CD2-mycER mice showed accelerated death on induction with tamoxifen at similar rates to CD2-mycER controls. Moreover, thymocytes from preleukaemic CD2-Cbfa1-G1 mice showed reduced survival in vitro and increased sensitivity to the inhibitory effects of TGF-beta. This study demonstrates that a full-length Cbf alpha-chain gene can act as an oncogene without fusion to a heterologous protein.

Animals↗

Cloning and mutational analysis of the Leptomonas seymouri U5 snRNA gene: function of the Sm site in core RNP formation and nuclear localization.

We have cloned the single-copy gene for the trans -spliceosomal U5 snRNA from the trypanosomatid species Leptomonas seymouri, using U5 RNA affinity selection and cDNA cloning. Sequence comparison revealed that the trans -spliceosomal U5 RNAs from trypanosomatid species share certain characteristic features. Interestingly, the affinity selection procedure yielded-in addition to the bona fide U5 RNA-a closely related small RNA, which can be folded into the same secondary structure, but carries three changes in the loop sequence. This raises the possibility that there may be a larger family of U5-like RNAs in trypanosomes. To study the U5 snRNP assembly and function in trypanosomes we have established a stable expression system in L.seymouri. Two cell lines have been generated that express U5 RNAs with mutations in the Sm site, resulting in a defect of core snRNP formation. In addition, the U5 Sm-mutant RNAs behaved differently in cell fractionation, implying a defect in nuclear localization. In sum, this demonstrates for the first time that the Sm site of trypanosome snRNAs contributes an essential element for stable core RNP assembly and may be important for nuclear localization, in analogy to the Sm site function of cis -spliceosomal snRNAs in higher eucaryotes.

Animals↗

Internal consistency, temporal stability and neuropsychological correlates of three cognitive components of the Positive and Negative Syndrome Scale (PANSS).

Comprehensive models of schizophrenia have increasingly included symptoms of cognitive dysfunction as an important feature of schizophrenia. Factor analytic studies of the Positive and Negative Syndrome Scale (PANSS) have consistently established cognitively disorganized symptoms as a separate domain from positive and negative symptoms. However, the individual symptom composition of the cognitive domain varies from model to model. The present study explores the temporal stability, internal consistency, concurrent validity, and discriminant validity for three published PANSS factor analytically derived cognitive components (Bell et al., 1994a, Psychiatry Res., 52, 295-303; Dollfus et al., 1991. Eur. Psychiatry, 6, 251-259; Kay and Sevy, 1990. Schizophr. Bull., 16, 537-544). Analyses were conducted using PANSS data from 120 patients with DSM-IV diagnoses of schizophrenia or schizoaffective disorder. Results indicate that the Bell et al. and Kay and Sevy models have similar psychometric properties including adequate temporal stability, internal consistency, and discriminant validity. The Kay model demonstrated somewhat better concurrent validity with cognitive test measures, while the Dollfus model demonstrated relatively poor psychometrics. The symptom composition of a narrowly defined cognitively disorganized subtype and a more broadly defined cognitively impaired subtype are discussed in terms of their value for schizophrenia research.

Adult↗

Imaging of asteroid 433 eros during NEAR's flyby reconnaissance

During the 23 December 1998 flyby of asteroid 433 Eros, the Near-Earth Asteroid Rendezvous (NEAR) spacecraft obtained 222 images of Eros, as well as supporting spectral observations. The images cover slightly more than two-thirds of Eros (best resolution is approximately 400 meters per pixel) and reveal an elongated, cratered body with a linear feature extending for at least 20 kilometers. Our observations show that Eros has dimensions of 33 x 13 x 13 kilometers. The volume, combined with the mass determined by the NEAR radio science experiment, leads to a density of 2.5 +/- 0.8 grams per cubic centimeter. This relatively high density, and the presence of an extensive linear feature, suggest that Eros may be a structurally coherent body.

Journal Article↗

Molecular cloning and characterization of the human topoisomerase IIalpha and IIbeta genes: evidence for isoform evolution through gene duplication.

Human DNA topoisomerase II is essential for chromosome segregation and is the target for several clinically important anticancer agents. It is expressed as genetically distinct alpha and beta isoforms encoded by the TOP2alpha and TOP2beta genes that map to chromosomes 17q21-22 and 3p24, respectively. The genes display different patterns of cell cycle- and tissue-specific expression, with the alpha isoform markedly upregulated in proliferating cells. In addition to the fundamental role of TOP2alpha and TOP2beta genes in cell growth and development, altered expression and rearrangement of both genes are implicated in anticancer drug resistance. Here, we report the complete structure of the human topoisomerase IIalpha gene, which consists of 35 exons spanning 27.5 kb. Sequence data for the exon-intron boundaries were determined and examined in the context of topoisomerase IIalpha protein structure comprising three functional domains associated with energy transduction, DNA breakage-reunion activity and nuclear localization. The organization of the 3' half of human TOP2beta, including sequence specifying the C-terminal nuclear localization domain, was also elucidated. Of the 15 introns identified in this 20 kb region of TOP2beta, the first nine and the last intron align in identical positions and display the same phases as introns in TOP2alpha. Though their extreme 3' ends differ, the striking conservation suggests the two genes diverged recently in evolutionary terms consistent with a gene duplication event. Access to TOP2alpha and TOP2beta gene structures should aid studies of mutations and gene rearrangements associated with anticancer drug resistance.

Amino Acid Sequence↗

Taxol-induced meiotic maturation delay, spindle defects, and aneuploidy in mouse oocytes and zygotes.

To increase our understanding about the potential risks of chemically-induced aneuploidy, more information about the various mechanisms of aneuploidy induction is needed, particularly in germ cells. Most chemicals that induce aneuploidy inhibit microtubule polymerization. However, taxol alters microtubule dynamics by enhancing polymerization and stabilizing the polymer fraction. We tested the hypothesis that taxol induces meiotic delay, spindle defects, and aneuploidy in mouse oocytes and zygotes. Super-ovulated ICR mice received 0 (control), 2.5, 5.0, and 7.5 mg/kg taxol intraperitoneally immediately after HCG. Females were paired (1:1) with males for 17 h after taxol treatment. Mated females were given colchicine 25 h after taxol and their one-cell zygotes were collected 16 h later. Ovulated oocytes from non-mated females were collected 17 h after taxol. Chromosomes were C-banded for cytogenetic analyses. Oocytes were also collected from another group of similarly treated females for in situ chromatin and microtubule analyses. Taxol significantly (p<0.01) enhanced the proportion of oocytes exhibiting parthenogenetic activation, chromosomes displaced from the meiotic spindle, and sister-chromatid separation. Moreover, 7.5 mg/kg taxol significantly (p<0.01) increased the proportions of metaphase I and diploid oocytes and polyploid zygotes. A significant (p<0.01) dose response for taxol-induced hyperploidy in oocytes and zygotes was found. These results support the hypothesis that taxol-induced meiotic delay and spindle defects contribute to aneuploid mouse oocytes and zygotes.

Aneuploidy↗

Development and testing of the Resistiveness to Care Scale.

A conceptual model and objective scale for measuring resistiveness to care in individuals with advanced dementia of the Alzheimer type (DAT) were empirically generated from the perspective of nursing staff caregivers and through observation of residents with DAT. The resistiveness to care scale (RTC-DAT) was judged to have content validity and reduced to 13 items. Quantifiable scoring procedures and methods for rating videotapes and conducting clinical observations were developed. The RTC-DAT was tested with 68 subjects at three sites. The RTC has a range of 0-156. Initial testing provided reliability estimates of .82-.87 for internal consistency and good to excellent kappas. Criterion-related validity with observed discomfort and construct validity by factor analysis support the RTC-DAT. Measurement issues and recommendations for use in research are discussed.

Activities of Daily Living↗

Depression and anxiety symptoms in women at high risk for breast cancer: pilot study of a group intervention.

OBJECTIVE: The psycho-oncology literature to date contains only one outcome study based on a group model for high-risk relatives of breast cancer patients. The authors set out to study the effects of group intervention in high-risk relatives of breast cancer patients. METHOD: Thirty-three high-risk relatives of breast cancer patients participated in a six-session, 12-hour group intervention model that consisted of educational and psychosocial components. RESULTS: There was a significant reduction of depression symptoms as reported on the Center for Epidemiologic Studies Depression Scale. Similarly, there was a significant reduction of anxiety symptoms as reported on the State-Trait Anxiety Inventory state scale. CONCLUSIONS: In this pilot study, the investigators found the group intervention model effective at reducing symptoms of depression and reactive (not chronic) anxiety.

Adaptation, Psychological↗

Sjögren's syndrome: a critical review of clinical management.

Sjögren's syndrome (SS) is greatly under recognized in clinical practice, primarily for 2 reasons: its presentations are variable and often nonspecific and there are still no clear, uniform diagnostic criteria for this clinical entity. The prevalence, natural history, pathogenesis, and clinical taxonomy of SS are still not well understood. Potential criteria include both subjective symptoms and objective criteria such as measurements of salivary and tear flow, minor salivary gland biopsy, and an increasing variety of serological markers. Physicians often fail to appreciate the profound impact of SS on quality of life. Therefore, screening for SS should include questions exploring symptoms in terms of their effect on the patient's daily life. At present, there is no curative treatment for SS. For symptom relief, local treatments (such as artificial tears or oral topical sprays) are limited in their effects, whereas systemic treatment offers the advantage of addressing a wider range of symptoms. Controlled studies show that oral pilocarpine significantly improves sicca symptoms in the eyes, mouth, and other sites. Clinical experience to date suggests it is safe and well tolerated, with no serious adverse effects, tachyphylaxis, or drug to drug interactions of concern. The most frequent adverse effects are sweating, urinary frequency, diarrhea, and other parasympathomimetic effects, but these do not lead to substantial drug withdrawal rates. Patients should be forewarned that subjective improvement may lag behind improvement in objective measures. Because management often spans several specialties, coordination among them is essential. Dental, gynecological, and ophthalmological perspectives on diagnosis and management are discussed; the primary practitioner has the opportunity to play both a coordinating role and a direct role in early diagnosis and treatment.

Combined Modality Therapy↗