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Biomedical subjects

A G Fisher

Publications and source records attributed to A G Fisher.

At least 19 recordsLinked to original sources

Aerobic exercise in water versus walking on land: effects on indices of fat reduction and weight loss of obese women.

AIM: It has been suggested, that water exercise is less effective than weight-bearing exercise on land for body fat reduction. METHODS: To test this hypothesis 38 middle-aged obese women (25-47% body fat) participated in a 13 week exercise-diet program to compare the effects of aerobic exercise in water versus walking on land on indices of fat reduction and weight loss changes. Subjects were randomly assigned to 1 of 3 exercise groups: 1) walking on land (WL), 2) swimming (SW) at 27 degrees C water temperature and 3) walking in 29 degrees C water (WW) at the shallow end of a declining pool with the water at navel height. Subjects in the SW group alternated breast-, side-, and backstroke swimming without face immersion. Exercise parameters were kept constant for all three groups. Subjects participated in supervised exercise sessions for 40 min, 4 times a week at 70% of age-predicted maximum heart rate. Subjects were tested before and after the 13-week experimental period. RESULTS: Significant reductions in body weight, (5.9 kg), percent body fat, (3.7%), and skinfold and girth measurements, occurred in all groups. There where no significant differences between groups. CONCLUSIONS: The results of this study indicate that there are no differences in the effect of aerobic activities in the water versus weight-bearing aerobic exercise on land on body composition components as long as similar intensity, duration and frequency are used.

Adult↗

Validity of a performance assessment of activities of daily living for people with developmental disabilities.

BACKGROUND: Since clients with different types of developmental disabilities often experience difficulties in activities of daily living (ADL), it is critical that assessments of ADL are evaluated in order to ensure that one can make valid judgements based on the results of the appraisal. The purpose of the present study was to evaluate the validity of a specific performance assessment instrument, the Assessment of Motor and Process Skills (AMPS), when used by occupational therapists with clients with developmental disabilities. Unlike global ADL assessments, the AMPS is used not only to evaluate the level of ADL dependence, but also to estimate the quality of each specific action performed when a person is performing ADL tasks. METHODS: Data were gathered from 1724 participants with different developmental disabilities, including intellectual disability (ID), cerebral palsy and spina bifida. Many-Facet Rasch (MFR) analysis was used to examine person-response validity, and task and item scale validity. RESULTS: Goodness-of-fit statistics showed that the tasks and items had acceptable scale validity. The participants had acceptable person-response validity on the ADL motor scale, but had slightly lower than expected levels of person-response validity on the ADL process scale. The results indicate that clients with more severe forms of ID may have a higher proportion of different performance profiles in ADL than is expected by the MFR model of the AMPS. Since the proportion of participants who did not meet the criteria was only 3% lower than expected and in accordance with other studies, the difference may not be clinically meaningful. Otherwise, the results indicated that the AMPS is a valid tool when used with clients with developmental disabilities. CONCLUSIONS: Further research is needed to evaluate the use of the AMPS in clinical assessment and intervention planning for this group of clients.

Activities of Daily Living↗

Sensory adaptation in naive peripheral CD4 T cells.

T cell receptor interactions with peptide/major histocompatibility complex (pMHC) ligands control the selection of T cells in the thymus as well as their homeostasis in peripheral lymphoid organs. Here we show that pMHC contact modulates the expression of CD5 by naive CD4 T cells in a process that requires the continued expression of p56(lck). Reduced CD5 levels in T cells deprived of pMHC contact are predictive of elevated Ca(2)+ responses to subsequent TCR engagement by anti-CD3 or nominal antigen. Adaptation to peripheral pMHC contact may be important for regulating naive CD4 T cell responsiveness.

Adaptation, Physiological↗

Evolutionary conservation, developmental expression, and genomic mapping of mammalian Twisted gastrulation.

The twisted gastrulation gene (tsg) encodes a secreted protein required for the correct specification of dorsal midline cell fate during gastrulation in Drosophila. We report that tsg homologs from human, mouse, zebrafish, and Xenopus share 72-98% identity at the amino acid level and retain all 24 cysteine residues from Drosophila. In contrast to Drosophila where tsg expression is limited to early embryos, expression is found throughout mouse and human development. In Drosophila, tsg acts in synergy with decapentaplegic (dpp), a member of the TGF-beta family of secreted proteins. The vertebrate orthologs of dpp, BMP-2 and -4, are crucial for gastrulation and neural induction, and aberrant signaling by BMPs and other TGF-beta family members results in developmental defects including holoprosencephaly (HPE). Interestingly, human TSG maps to the HPE4 locus on Chromosome 18p11.3, and our analysis places the gene within 5 Mbp of TG-interacting factor (TGIF).

Amino Acid Sequence↗

Expression of alpha- and beta-globin genes occurs within different nuclear domains in haemopoietic cells.

The alpha- and beta-globin gene clusters have been extensively studied. Regulation of these genes ensures that proteins derived from both loci are produced in balanced amounts, and that expression is tissue-restricted and specific to developmental stages. Here we compare the subnuclear location of the endogenous alpha- and beta-globin loci in primary human cells in which the genes are either actively expressed or silent. In erythroblasts, the alpha- and beta-globin genes are localized in areas of the nucleus that are discrete from alpha-satellite-rich constitutive heterochromatin. However, in cycling lymphocytes, which do not express globin genes, the distribution of alpha- and beta-globin genes was markedly different. beta-globin loci, in common with several inactive genes studied here (human c-fms and SOX-1) and previously (mouse lambda5, CD4, CD8alpha, RAGs, TdT and Sox-1), were associated with pericentric heterochromatin in a high proportion of cycling lymphocytes. In contrast, alpha-globin genes were not associated with centromeric heterochromatin in the nucleus of normal human lymphocytes, in lymphocytes from patients with alpha-thalassaemia lacking the regulatory HS-40 element or entire upstream region of the alpha-globin locus, or in mouse erythroblasts and lymphocytes derived from human alpha-globin transgenic mice. These data show that the normal regulated expression of alpha- and beta-globin gene clusters occurs in different nuclear environments in primary haemopoietic cells.

Cell Nucleus↗

Nonequivalent nuclear location of immunoglobulin alleles in B lymphocytes.

Individual B lymphocytes normally express immunoglobulin (Ig) proteins derived from single Ig heavy chain (H) and light chain (L) alleles. Allelic exclusion ensures monoallelic expression of Ig genes by each B cell to maintain single receptor specificity. Here we provide evidence that at later stages of B cell development, additional mechanisms may contribute to prioritizing expression of single IgH and IgL alleles. Fluorescent in situ hybridization analysis of primary splenic B cells isolated from normal and genetically manipulated mice showed that endogenous IgH, kappa and lambda alleles localized to different subnuclear environments after activation and had differential expression patterns. However, this differential recruitment and expression of Ig alleles was not typically seen among transformed B cell lines. These data raise the possibility that epigenetic factors help maintain the monoallelic expression of Ig.

Alleles↗

An assessment of various household food security measures in Hawaiì has implications for national food security research and monitoring.

The Core Food Security Module (CFSM), the national food security monitoring tool, requires three affirmative responses to categorize households as food insecure. If this tool is unreliable or inaccurate, vulnerable segments of our population may be adversely affected. The objectives of the present study were to assess the credibility of applying the CFSM categorical measure to a population sample from Hawaiì and to assess the concurrent validity of the CFSM, the new face-valid measure and measures adapted from the Radimer/Cornell (RC) measure and Community Childhood Hunger Identification Project. The sample included 1469 respondents gathered through a statewide telephone sample and 144 food pantry recipients. Responses to the 18 CFSM questions were used to create all four measures. The credibility of the CFSM categorical measure was also assessed via comparisons with individual items and with the 1995 national modal CFSM response pattern. Categorical measures were compared across food security prevalence estimates and indices of income and vegetable intake and with the CFSM scale measure. Differences in the modal response pattern between samples affected CFSM categorization. Only 36% of households followed the Hawaiì modal response pattern, and categorization was not consistent with the content of key items. Although 85% of the households were classified as food secure by the CFSM, only 78% were classified as food secure with each of the other food security measures. Concurrent validity of all measures was confirmed. A reassessment of the national CFSM categorical measure appears warranted.

Adult↗

Stroke volume does not plateau during graded exercise in elite male distance runners.

UNLABELLED: Stroke volume (SV) responses during graded treadmill exercise were studied in 1) elite male distance runners (N = 5), 2) male university distance runners (N = 10), and 3) male untrained university students (N = 10). METHODS: Cardiac output (Q) and SV were determined by a modified acetylene rebreathing procedure. RESULTS: There were no differences in SV responses among the three groups during the transition from rest to light exercise (P > 0.05). However, the rates of change of SV during light to maximal exercise in untrained subjects (slope = -0.1544 mL x beat(-1)) and university distance runners (slope = 0.1041) did not change, whereas it dramatically increased (P < 0.001) in elite distant runners (slope = 0.6734). Moreover, the elite distance runners showed a further slope increase in SV when heart rate was above 160 bpm, which resulted in an average maximal SV of 187 +/- 14 mL x beat(-1) compared with 145 +/- 8 and 128 +/- 14 mL x beat(-1) in the university runners and untrained students, respectively (P < 0.001). Similarly, max Q reached 33.8 +/- 2.3, 26.3 +/- 1.7, and 21.3 +/- 1.5 L x min(-1) in the three groups, respectively (P < 0.001). On the other hand, there was a nonsignificant tendency for maximal arteriovenous oxygen content difference to be lower in the elite athletes compared with the other groups. CONCLUSION: Results from university distance runners and untrained university students support the classic observation that SV plateaus at about 40% of maximal oxygen consumption despite increasing intensity of exercise. In contrast, stroke volume in the elite athletes does not plateau but increases continuously with increasing intensity of exercise over the full range of the incremental exercise test.

Adult↗

The alternate forms reliability of the new tasks added to the Assessment of Motor and Process Skills.

The purpose of this study was to evaluate the alternate forms reliability of new tasks vs. old tasks of the Assessment of Motor and Process Skills (AMPS). The participants in this study were 44 persons taken from the AMPS database who had completed two old tasks and two new tasks within a 4-day period. Paired t tests revealed no significant difference between the means of ADL ability measures based on the performance of new vs. old tasks. The Pearson product moment correlations between the ADL ability measures based on the performance of new vs. old tasks was r =.92, p <.001 for motor ability measures and r =.77, p <.001 for process ability measures. We found that 100% of the ADL motor ability measures had standardized differences less than 2.00 (p <.05) and 97% of the ADL process ability measures had standardized differences less than 2.00 (p <.05). Considered together, the results support good alternate forms reliability of the ADL motor and ADL process ability measures. This study supported the finding that the 20 newly calibrated IADL and PADL tasks can be used reliably in clinical practice. When the AMPS is used to evaluate change, we can have 80 to 93% confidence that paired ability measures that change by more than +0.5 logits are the result of actual changes in ability.

Activities of Daily Living↗

Targeting of Ikaros to pericentromeric heterochromatin by direct DNA binding.

Ikaros is a sequence-specific DNA-binding protein that is essential for lymphocyte development. Little is known about the molecular function of Ikaros, although recent results have led to the hypothesis that it recruits genes destined for heritable inactivation to foci containing pericentromeric heterochromatin. To gain further insight into the functions of Ikaros, we have examined the mechanism by which it is targeted to centromeric foci. Efficient targeting of Ikaros was observed upon ectopic expression in 3T3 fibroblasts, demonstrating that lymphocyte-specific proteins and a lymphoid nuclear architecture are not required. Pericentromeric targeting did not result from an interaction with the Mi-2 remodeling factor, as only a small percentage of Mi-2 localized to centromeric foci in 3T3 cells. Rather, targeting was dependent on the amino-terminal DNA-binding zinc finger domain and carboxy-terminal dimerization domain of Ikaros. The carboxy-terminal domain was required only for homodimerization, as targeting was restored when this domain was replaced with a leucine zipper. Surprisingly, a detailed substitution mutant analysis of the amino-terminal domain revealed a close correlation between DNA-binding and pericentromeric targeting. These results show that DNA binding is essential for the pericentromeric localization of Ikaros, perhaps consistent with the presence of Ikaros binding sites within centromeric DNA repeats. Models for the function of Ikaros that are consistent with this targeting mechanism are discussed.

3T3 Cells↗

Different doses of agonistic ligand drive the maturation of functional CD4 and CD8 T cells from immature precursors.

MHC molecules are normally required for the development of thymocytes from the CD4(+)CD8(+) double-positive to the CD4 or CD8 single-positive stage. Here we show that mitogenic plant lectins can substitute for MHC molecules in driving the differentiation of phenotypically and functionally mature CD4 as well as CD8 T cells. Interestingly, lectin dosage determines whether CD4 or CD8 cells are generated, indicating that variation of cumulative signal strength (not necessarily signal quality) can result in an apparent switching of lineage preference. Thymocyte perception of differentiation-inducing signals is modulated by the cellular context, since stimuli that yield CD8 cells in the context of the thymic microenvironment fail to do so in suspension culture and generate CD4 progeny instead. Finally, we show that lectin-generated single-positive thymocytes retain the ability to respond to the ligands initially used to drive their differentiation. Our results call into question generalizations and predictions made from other experimental systems and reveal that thymocyte selection is considerably more flexible than had been anticipated.

Animals↗

The core food security module scale measure is valid and reliable when used with Asians and Pacific Islanders.

The Core Food Security Measure (CFSM) is used nationally to assess the extent and severity of household food insecurity in the previous 12 mo due to inadequate money for food. Both a scale measure and a categorical measure were developed from a national cross-sectional sample. The objective of this research was to determine whether the CFSM scale measure is a reliable and valid food security measure for use in Hawaii, where at least 50% of the population is of Asian or Pacific Islander descent. We completed an independent assessment of the robustness of the internal scale construct validity of the CSFM scale measure and hierarchical order of items using the same Rasch methods used previously to develop the CSFM. From a sample of 1664 respondents, data from 362 were used in the Rasch analysis. Item goodness-of-fit statistics indicated that responses to the "adults cut the size or skip meals" item and its follow-up item were redundant [outfit mean-square residual (MnSq) = 0.6, z = -2]. Responses to the "(un)able to eat balanced meals" item were erratic (outfit MnSq = 2.1, z = 2). Findings pertaining to goodness-of-fit of the respondents indicated an acceptable rate of misfit (4.7%). Rate of misfit did not vary with family status or with any ethnic group except the Samoans. Overall, the CFSM scale measure fit as well with the Hawaii data as it did with national data, although identified limitations may affect food security monitoring and research.

Adult↗

Naturalistic assessment of functional performance in school settings: reliability and validity of the School AMPS scales.

The School Assessment of Motor and Process Skills (School AMPS) is an assessment tool designed to be used by occupational therapists to measure the effectiveness of a student's ability to perform school tasks in naturalistic classroom settings. Rater reliability, internal scale validity, and person response validity of the School AMPS was investigated by examining the goodness-of-fit of raters, motor and process skill items, and students to the many-faceted Rasch model used in the development of the School AMPS. Five of six raters demonstrated acceptable goodness-of-fit (MnSq < or = 1.4 and z < 2). All 36 motor and process skill items demonstrated acceptable goodness-of-fit. Of the 208 students in the study, 93.7% demonstrated acceptable goodness-of-fit on the School AMPS motor scale and 88.9% demonstrated acceptable goodness-of-fit on the School AMPS process scale. The results of this study support the rater reliability, scale validity, and person response validity for the School AMPS as a tool to be used to evaluate the effectiveness of student performance of school tasks in the classroom setting.

Activities of Daily Living↗

Intrathymic deletion of MHC class I-restricted cytotoxic T cell precursors by constitutive cross-presentation of exogenous antigen.

Cross-priming of cytotoxic T lymphocytes by professional antigen-presenting cells (APC) is a potential hazard to self tolerance because it exposes naive T cells to tissue-specific self antigens in the context of co-stimulatory signals. Here we show that cross-presentation of exogenous material occurs constitutively within the thymus. Although efficient cross-presentation is a property of relatively few APC it results in thymocyte deletion both in vitro and in vivo, suggesting that intrathymic cross-presentation can operate as an effective component of tolerance to circulating self antigens. The capacity of minor cell populations to mediate thymocyte deletion but not positive selection reflects an underlying difference in the biology of these two processes.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Dynamic repositioning of genes in the nucleus of lymphocytes preparing for cell division.

We show that several transcriptionally inactive genes localize to centromeric heterochromatin in the nucleus of cycling but not quiescent (noncycling) primary B lymphocytes. In quiescent cells, centromeric repositioning of inactive loci was induced after mitogenic stimulation. A dynamic repositioning of selected genes was also observed in developing T cells. Rag and TdT loci were shown to relocate to centromeric domains following heritable gene silencing in primary CD4+8+ thymocytes, but not in a phenotypically similar cell line in which silencing occurred but was not heritable. Collectively, these data indicate that the spatial organization of genes in cycling and noncycling lymphocytes is different and that locus repositioning may be a feature of heritable gene silencing.

Alleles↗

Alternate forms reliability of the assessment of motor and process skills.

The purpose of this study is to examine the alternate forms reliability of the AMPS (Assessment of Motor and Process Skills) (Fisher, 1997a) where alternate forms means different pairs of AMPS tasks. The participants for this study were persons selected from the AMPS database who had performed four AMPS tasks. The participants varied in age, gender, diagnosis, and level of assistance needed to live in the community. The AMPS was administered by trained and calibrated occupational therapists according to standardized procedures. The data for the 91 participants were subjected to 12 many-faceted Rasch analyses to generate ADL motor and ADL process ability measures for each task and each set of paired tasks. Repeated measures ANOVAs revealed no time effect across the four AMPS tasks. Pearson product moment correlations between Tasks 1 and 2 combined and Tasks 3 and 4 combined were r = .91 and r = .86 for the ADL motor and ADL process scales, respectively. Calculation of the standardized difference (z) revealed that no more than 8% of the participants had ADL motor or ADL process ability measures that differed significantly between observations once we accounted for real differences in a persons performance; 80% of the paired ADL motor and ADL process ability measures remained stable within +/- 0.5 logits when the participants performed two tasks. The AMPS ADL motor and ADL process scales can be used reliably in clinical practice and for research purposes.

Activities of Daily Living↗

Helios, a T cell-restricted Ikaros family member that quantitatively associates with Ikaros at centromeric heterochromatin.

The Ikaros gene encodes multiple protein isoforms that contribute critical functions during the development of lymphocytes and other hematopoietic cell types. The intracellular functions of Ikaros are not known, although recent studies have shown that Ikaros proteins colocalize with inactive genes and centromeric heterochromatin. In this study, Ikaros proteins were found to be components of highly stable complexes. The complexes from an immature T cell line were purified, revealing associated proteins of 70 and 30 kD. The p70 gene, named Helios, encodes two protein isoforms with zinc finger domains exhibiting considerable homology to those within Ikaros proteins. Helios and Ikaros recognize similar DNA sequences and, when overexpressed, Helios associates indiscriminately with the various Ikaros isoforms. Although Ikaros is present in most hematopoietic cells, Helios was found primarily in T cells. The relevance of the Ikaros-Helios interaction in T cells is supported by the quantitative association of Helios with a fraction of the Ikaros. Interestingly, the Ikaros-Helios complexes localize to the centromeric regions of T cell nuclei, similar to the Ikaros localization previously observed in B cells. Unlike the B cell results, however, only a fraction of the Ikaros, presumably the fraction associated with Helios, exhibited centromeric localization in T cells. These results establish immunoaffinity chromatography as a useful method for identifying Ikaros partners and suggest that Helios is a limiting regulatory subunit for Ikaros within centromeric heterochromatin.

Amino Acid Sequence↗