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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
PubMed1999

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↗
PubMed1999

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↗
PubMed1998

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↗
PubMed1998

Environment effect of functional task performance in adults with acquired brain injuries: use of the assessment of motor and process skills.

OBJECTIVE: To examine household task performance in both familiar (home) and unfamiliar (clinic) environments in adults with acquired brain injuries. DESIGN: The research performed was a comparison study examining the effect of the environment on functional task performance. Individuals were evaluated using the Assessment of Motor and Process Skills both in their homes and in an unfamiliar clinic setting. PARTICIPANTS: Twenty individuals with acquired brain injuries living in the community. MAIN OUTCOME MEASURES: The Assessment of Motor and Process Skills, an observational, standardized, occupational therapy assessment tool, was used to evaluate household task performance. RESULTS: Paired one-tailed t tests indicated a significant difference between home and clinic performance measures in process ability (t=-4.28, p=.00), but no significant difference in motor ability performance measures (t=-1.84, p=.410). Scatter plot analyses showed that performance scores of 6 of the 20 subjects differed in a clinically meaningful way, and that instrumental activities of daily living motor performance scores for 3 of the 20 differed in a clinically meaningful way. CONCLUSIONS: Individuals with acquired brain injuries may be influenced by their environment when performing household tasks, although further study is necessary to determine the extent of the environmental effect.

Activities of Daily Living↗
PubMed1998

The dimensionality and validity of the Older Americans Resources and Services (OARS) Activities of Daily Living (ADL) Scale.

The psychometric properties of the OARS ADL scale, comprised of seven physical activities of daily living (PADL) and seven instrumental activities of daily living (IADL) items, were examined using a Rasch measurement approach. Two of the PADL items failed to demonstrate acceptable goodness-of-fit with the measurement model but the remaining 12 items could be combined into a single measure of ADL ability. Although the OARS ADL scale was designed to identify those community-dwelling elderly who need supports and services to continue to live in the community, the scale items were found to be poorly targeted to community-dwelling elderly since almost half of our sample received maximal scores. Rasch analysis identified how we might improve the sensitivity of the OARS ADL scale but its utility in outcome and longitudinal studies remains questionable.

Activities of Daily Living↗
PubMed1997

Association of transcriptionally silent genes with Ikaros complexes at centromeric heterochromatin.

Ikaros proteins are required for normal T, B, and NK cell development and are postulated to activate lymphocyte-specific gene expression. Here we examined Ikaros distribution in the nucleus of B lymphocytes using confocal microscopy and a novel immunofluorescence in situ hybridization (immuno-FISH) approach. Unexpectedly, Ikaros localized to discrete heterochromatin-containing foci in interphase nuclei, which comprise clusters of centromeric DNA as defined by gamma-satellite sequences and the abundance of heterochromatin protein-1 (HP-1). Using locus-specific probes for CD2, CD4, CD8alpha, CD19, CD45, and lambda5 genes, we show that transcriptionally inactive but not transcriptionally active genes associate with Ikaros-heterochromatin foci. These findings support a model of organization of the nucleus in which repressed genes are selectively recruited into centromeric domains.

Animals↗
PubMed1997

How many thymocytes audition for selection?

T cell maturation requires the rearrangement of clonotypic T cell receptors (TCR) capable of interacting with major histocompatibility complex (MHC) ligands to initiate positive and negative selection. Only 3-5% of thymocytes mature to join the peripheral T cell pool. To investigate the basis for this low success rate, we have measured the frequency of preselection thymocytes capable of responding to MHC. As many as one in five MHC-naive thymocytes show upregulation of activation markers on exposure to MHC-expressing thymic stroma in short-term reaggregate culture. The majority of these cells display physiological changes consistent with entry into the selection process within 24 h. By exposing TCR transgenic thymocytes to a range of MHC-peptide complexes, we show that CD69 induction is indicative of thymocyte selection, positive or negative. Our data provide evidence that the fraction of thymocytes that qualify to enter the thymic selection process far exceeds the fraction that successfully complete it, and suggest that most MHC-reactive thymocytes are actively eliminated in the course of selection.

Animals↗
PubMed1997

Rational primer design greatly improves differential display-PCR (DD-PCR).

Since its conception in 1992, differential display PCR (DD-PCR) has attracted widespread interest. Theoretically an attractive cloning approach, it combines the comparative analysis of several samples with the sensitivity of PCR. Although a large number of studies embracing this technology have been initiated, few novel genes of interest have been identified, suggesting that the method has not realised its potential. The present report shows that by modifying primer design, sampling of differentially expressed genes can be greatly enhanced and relevant genes can be isolated. Using our modified conditions DD-PCR efficiently screens a wide range of gene expression levels, in which differences are represented on a linear scale.

Animals↗
PubMed1997

Measuring functional competence in older persons with Alzheimer's disease.

Despite their limitations, mental status tests and self/proxy reports of instrumental activities of daily living (IADL) are often used to predict functional competence. In contrast, the Assessment of Motor and Process Skills (AMPS) is a direct observational assessment of IADL competence. Sixty-four community-dwelling elderly (20 Alzheimer's disease [AD] patients and 44 nondemented) were assessed with the AMPS, the Mini-Mental State Examination (MMSE), and the Older Americans Resources and Services (OARS)-IADL. Performance on all three assessments was significantly lower for the AD sample. The MMSE did not correlate significantly with the AMPS motor ability measures but it correlated modestly with the AMPS process ability measures. The OARS-IADL correlated significantly with the AMPS motor ability measure for the nondemented sample alone. Although mental status and self/proxy assessments provide some insight into individuals' IADL competence, direct observation of IADL task performance provides additional information regarding the subtle process and motor skills changes that occur in progressive dementing conditions.

Activities of Daily Living↗
PubMed1997

Effects of familiarity of task and choice on the functional performance of younger and older adults.

An experiment was conducted to compare the functional performance of younger and older adults on familiar and unfamiliar tasks under 2 conditions of perceived control. Specifically, the relation between age and motor and process skills was examined. The familiar tasks were simple cooking tasks, whereas the unfamiliar tasks were contrived, meaningless tasks developed for this study. Younger and older adults did not differ in the ratings of the familiarity of the tasks, but results from 2 Age x Task x Choice analyses of variance demonstrated a significant age difference for motor and process skills under all conditions. This suggests that older adults demonstrate age-related decline, even with activities that take motivational, experiential, and ecological validity components into account. For the process skills scale, there was also a significant main effect for choice. These results support the concept that perceived control may improve performance, but not differentially for older adults; that is, younger and older adults both demonstrated improved process performance when given their choice of tasks.

Activities of Daily Living↗
PubMed1996

Male and female performance on the assessment of motor and process skills.

OBJECTIVE: To examine the validity of the assertion that men and women do not differ significantly on the Assessment of Motor and Process Skills (AMPS), a functional assessment tool used to evaluate the interaction between component motor and process skills and IADL (instrumental or domestic activities of daily living) performance capacity. DESIGN: Descriptive comparison. Using many-faceted Rasch analysis, the AMPS motor and process scales were examined for differential item response between gender subgroups. Mean motor and process ability measures of age-matched groups of male and female subjects were also compared. PARTICIPANTS: A convenience sample of more than 3,500 men and women from the standardization sample for the pilot version of the AMPS computer-scoring software. The subjects had a variety of physical disabilities or psychiatric diagnoses. MAIN OUTCOME MEASURES: Hypotheses were as follows: (1) no differential item response would be found on the motor or process scales; (2) if differential item response was found, it would not have an impact on the final estimation of client ability; (3) men and women would not differ in mean AMPS motor or process ability. RESULTS: Of the 36 AMPS items, only one (Lifts) differed between men and women. This differential item response did not disrupt the final estimation of client ability. Men and women did not differ in mean motor ability. Women on the whole were more able than men in mean process ability. CONCLUSIONS: The AMPS is valid for use across gender subgroups. Men and women do not differ in AMPS motor ability, but overall, women are slightly more able than men in AMPS process ability.

Activities of Daily Living↗
PubMed1995

Differences between persons with right or left cerebral vascular accident on the Assessment of Motor and Process Skills.

OBJECTIVE: Persons with right and left cerebral vascular accident (RCVA and LCVA) differ in terms of discrete impairments, but there is limited information with regard to how such impairments translate into differences in disability. The following hypotheses were tested: (1) persons with stroke have lower instrumental or domestic activities of daily living (IADL) ability than do matched nondisabled controls, (2) persons with RCVA do not differ from persons with LCVA in IADL ability, and (3) persons with RCVA and LCVA differ in specific motor and process skills that affect IADL performance. DESIGN: Descriptive comparison. SETTING: Subjects were tested in settings where rehabilitation services were received (home or clinic). SUBJECTS: 71 persons with RCVA, 76 persons with LCVA, and 83 community-living nondisabled individuals drawn from the Assessment of Motor and Process Skills (AMPS) database, matched for age, gender, and number of tasks performed. MAIN OUTCOME MEASURE: AMPS, designed to measure type and severity of impairments manifested in the context of IADL performance. The AMPS was administered to all subjects in accordance with standardized testing procedures. RESULTS: The two stroke groups did not differ significantly in IADL ability, but both stroke groups had significantly lower IADL performance than did the nondisabled subjects. On the AMPS motor scale, persons with RCVA demonstrated greater impairment in pacing, transporting, and coordinating two body parts. Persons with LCVA demonstrated greater impairments in calibrating movements. No differences were found between the two groups in AMPS process skills. CONCLUSIONS: Persons with RCVA and LCVA have hemisphere-specific differences in motor impairments, but do not differ significantly in IADL ability.

Activities of Daily Living↗
PubMed1995

Lymphoproliferative disorders in IL-7 transgenic mice: expansion of immature B cells which retain macrophage potential.

Transgenic mice carrying the murine IL-7 gene under the MHC class II (E alpha) promoter are described which develop lymphoid tumours at a high incidence when maintained in conventional or specific pathogen-free environments. Cells obtained from the lesions were relatively monomorphic, expressed a variety of B cell associated markers (BP-1, B220, CD43) but lacked surface Ig. Some mice, showed expanded populations of cells phenotypically similar to the recently reported bipotent B/macrophage stem cell subset (AA4.1high, B220-, Ig-) which could be cloned and maintained in vitro. These cells expressed IL-7 receptors, proliferated in response to IL-7 and in most cases had germline configuration of the Ig heavy chain locus. Cell lines cloned from two such tumours generated macrophages spontaneously in culture, consistent with their bipotent B cell/macrophage phenotype. These results suggest that IL-7 plays a role in very early stages of B cell ontogeny prior to bona fide B cell commitment.

Animals↗
PubMed1995

Does the Q angle reflect the force on the patella in the frontal plane?

BACKGROUND AND PURPOSE: The quadriceps femoris muscle angle (Q angle) is used to reflect the quadriceps femoris muscle's force on the patella in the frontal plane. We found no studies, however, that validate this assumption. The purpose of this study was to determine whether the Q angle can be used to represent the force on the patella in the frontal plane. SUBJECTS: Seven lower extremities from four male cadavers were dissected and investigated. METHODS: We devised a model in which the line of action of quadriceps femoris muscle's resultant force was calculated in the frontal plane on the seven lower-extremity specimens. We then compared these calculations with the Q angles from the same cadaver specimens. The differences between the measured and calculated Q angles were tested for significance using a paired t test. In addition, we calculated a simple linear regression to test the relationship between the calculated and measured Q angles. RESULTS: Our data showed that the angle for the average resultant force of the quadriceps femoris muscle was 3.90 degrees greater (P = .0003) than the measured Q angles. A significant relationship (r = .919, P = .0035); however, was found between the measured and calculated Q angles. CONCLUSION AND DISCUSSION: The Q angle, as measured in clinical practice, appears to reflect the angle of the resultant quadriceps femoris muscle force. We believe, however, that this measurement is significantly less than the actual quadriceps femoris muscle force vector and underestimates the lateral force on the patella.

Biomechanical Phenomena↗
PubMed1995

Expression of functional MHC class II molecules by a mouse pro-B cell clone.

We describe here the G12 pro-B cell clone that has been isolated from an IL-7 transgenic mouse. This clone has the phenotype B220+, BP-1+, HSA+, CD43+, lambda5+, and CD25-, and has its Ig locus in a germline configuration. G12 cells spontaneously express cell-surface MHC class II molecules, although to a much lesser extent than the mature M12.4.1 B-cell lymphoma. G12 cells can process and present the native Hen Egg Lysozyme (HEL) to an MHC class II-restricted T-cell hybridoma. The efficiency of presentation is inferior to that obtained with M12.4.1 cells. This is the first report where a pro-B cell can serve as APC in an MHC class II-restricted presentation.

Animals↗
PubMed1994

In vitro construction of graded thymus chimeras.

A simple in vitro approach is described for constructing chimeric thymi in which the degree of chimeric contribution can be tightly controlled. This is achieved by protease-assisted dissociation of fresh fetal thymic tissue, mixing the resulting cell suspensions at the desired ratios, and subsequent reaggregation. Analysis of these graded chimeras shows that stromal elements become evenly interspersed and form a microenvironment able to support the maturation of endogenous T cell precursors. Chimeras between normal and MHC-deficient thymi have been used to demonstrate the rescue of mutant, allotype-marked thymocytes by wild-type stromal cells. Other potential applications of the method include quantitative studies on positive and negative thymic selection, the functional role of defined stromal cell types in these processes, and the analysis of mutants (either natural or engineered) by complementation.

Animals↗
PubMed1994

Functional competence of community-dwelling persons with multiple sclerosis using the assessment of motor and process skills.

The Assessment of Motor and Process Skills (AMPS) is an observational measure of functional competence in instrumental activities of daily living (IADL) that was designed to overcome the limitations of self reports and proxy reports. The AMPS allows simultaneous evaluation of the underlying motor and process (organizational/adaptive) skills necessary for competent task performance. We examined the IADL performance of 22 community-dwelling patients with mild to moderate MS in comparison to nondisabled subjects matched for age and gender. Functional competence of the MS subjects, as measured by the AMPS, was poorer than that of the control group. Many MS subjects who would not have been expected to have IADL difficulties on the basis of ratings of neurologic impairment were impaired in their IADL performance. For some patients, IADL impairment reflected deficits in their motor and process skills, whereas for others, process skill impairments alone were responsible for deficient task performance.

Activities of Daily Living↗