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Biomedical subjects

A M Myers

Publications and source records attributed to A M Myers.

At least 19 recordsLinked to original sources

Controlled outcome evaluation of the First Step Program: a daily physical activity intervention for individuals with type II diabetes.

OBJECTIVE: To conduct a randomised trial of a physical activity (PA) intervention, The First Step Program (FSP) for adults with type II diabetes. DESIGN: A 16-week intervention study and 24-week follow-up assessment. PARTICIPANTS: A total of 47 overweight/obese, sedentary individuals (age=52.7 +/- 5.2 y; BMI=33.3 +/- 5.6 kg/m2) recruited through a diabetes education centre. MEASUREMENTS PRIMARY OUTCOME: daily PA assessed by pedometer (steps/day). SECONDARY OUTCOMES: anthropometric measures (weight, BMI, waist girth, hip girth); indicators of cardiovascular health (resting heart rate and blood pressure); glycemic control (fasting glucose, insulin, HbA1c, glucose concentration 120 min postglucose load); plasma lipid status (total cholesterol, HDL cholesterol, LDL cholesterol, and triglycerides). RESULTS: Relative to the CONTROL group, FSP participants increased their PA >3000 steps/day (approximately 30 min/day) during the intervention (P<0.0001). Waist and hip girth decreased (approximately 2-3 cm), but did not differ significantly between groups. Significant changes did not emerge for any of the other variables. CONCLUSIONS: The FSP is a practical intervention that elicits an immediate and profound change in walking behaviour. Such change is an important 'first step' towards increasing the volume and/or intensity of PA necessary to improve long-term health outcomes in this largely sedentary and overweight or obese population. Relapse by 24 weeks indicates that other strategies such as booster sessions are needed to maintain lifestyle change. Further research must determine realistic and responsive health outcomes for this population that are achievable through practical, real-world programming.

Adult↗

Methodological considerations for researchers and practitioners using pedometers to measure physical (ambulatory) activity.

Researchers and practitioners require guidelines for using electronic pedometers to objectively quantify physical activity (specifically ambulatory activity) for research and surveillance as well as clinical and program applications. Methodological considerations include choice of metric and length of monitoring frame as well as different data recording and collection procedures. A systematic review of 32 empirical studies suggests we can expect 12,000-16,000 steps/day for 8-10-year-old children (lower for girls than boys); 7,000-13,000 steps/day for relatively healthy, younger adults (lower for women than men); 6,000-8,500 steps/day for healthy older adults; and 3,500-5,500 steps/day for individuals living with disabilities and chronic illnesses. These preliminary recommendations should be modified and refined, as evidence and experience using pedometers accumulates.

Adolescent↗

Molecular structure of three mutations at the maize sugary1 locus and their allele-specific phenotypic effects.

Starch production in all plants examined is altered by mutations of isoamylase-type starch-debranching enzymes (DBE), although how these proteins affect glucan polymer assembly is not understood. Various allelic mutations in the maize (Zea mays) gene sugary1 (su1), which codes for an isoamylase-type DBE, condition distinct kernel phenotypes. This study characterized the recessive mutations su1-Ref, su1-R4582::Mu1, and su1-st, regarding their molecular basis, chemical phenotypes, and effects on starch metabolizing enzymes. The su1-Ref allele results in two specific amino acid substitutions without affecting the Su1 mRNA level. The su1-R4582::Mu1 mutation is a null allele that abolishes transcript accumulation. The su1-st mutation results from insertion of a novel transposon-like sequence, designated Toad, which causes alternative pre-mRNA splicing. Three su1-st mutant transcripts are produced, one that is nonfunctional and two that code for modified SU1 polypeptides. The su1-st mutation is dominant to the null allele su1-R4582::Mu1, but recessive to su1-Ref, suggestive of complex effects involving quaternary structure of the SU1 enzyme. All three su1- alleles severely reduce or eliminate isoamylase-type DBE activity, although su1-st kernels accumulate less phytoglycogen and Suc than su1-Ref or su1-R4582::Mu1 mutants. The chain length distribution of residual amylopectin is significantly altered by su1-Ref and su1-R4582::Mu1, whereas su1-st has modest effects. These results, together with su1 allele-specific effects on other starch- metabolizing enzymes detected in zymograms, suggest that total DBE catalytic activity is the not the sole determinant of Su1 function and that specific interactions between SU1 and other components of the starch biosynthetic system are required.

Alleles↗

Two loci control phytoglycogen production in the monocellular green alga Chlamydomonas reinhardtii.

The STA8 locus of Chlamydomonas reinhardtii was identified in a genetic screen as a factor that controls starch biosynthesis. Mutations of STA8 cause a significant reduction in the amount of granular starch produced during nutrient limitation and accumulate phytoglycogen. The granules remaining in sta8 mutants are misshapen, and the abundance of amylose and long chains in amylopectin is altered. Mutations of the STA7 locus, which completely lack isoamylase activity, also cause accumulation of phytoglycogen, although sta8 and sta7 mutants differ in that there is a complete loss of granular starch in the latter. This is the first instance in which mutations of two different genetic elements in one plant species have been shown to cause phytoglycogen accumulation. An analytical procedure that allows assay of isoamylase in total extracts was developed and used to show that sta8 mutations cause a 65% reduction in the level of this activity. All other enzymes known to be involved in starch biosynthesis were shown to be unaffected in sta8 mutants. The same amount of total isoamylase activity (approximately) as that present in sta8 mutants was observed in heterozygous triploids containing two sta7 mutant alleles and one wild-type allele. This strain, however, accumulates normal levels of starch granules and lacks phytoglycogen. The total level of isoamylase activity, therefore, is not the major determinant of whether granule production is reduced and phytoglycogen accumulates. Instead, a qualitative property of the isoamylase that is affected by the sta8 mutation is likely to be the critical factor in phytoglycogen production.

Amylopectin↗

Biochemical characterization of wild-type and mutant isoamylases of Chlamydomonas reinhardtii supports a function of the multimeric enzyme organization in amylopectin maturation.

Chlamydomonas reinhardtii mutants of the STA8 gene produce reduced amounts of high amylose starch and phytoglycogen. In contrast to the previously described phytoglycogen-producing mutants of C. reinhardtii that contain no residual isoamylase activity, the sta8 mutants still contained 35% of the normal amount of enzyme activity. We have purified this residual isoamylase and compared it with the wild-type C. reinhardtii enzyme. We have found that the high-mass multimeric enzyme has reduced its average mass at least by one-half. This coincides with the disappearance of two out of the three activity bands that can be seen on zymogram gels. Wild-type and mutant enzymes are shown to be located within the plastid. In addition, they both act by cleaving off the outer branches of polysaccharides with no consistent difference in enzyme specificity. Because the mutant enzyme was demonstrated to digest phytoglycogen to completion in vitro, we propose that its inability to do so in vivo supports a function of the enzyme complex architecture in the processing of pre-amylopectin chains.

Amylopectin↗

Challenges and opportunities for measuring physical activity in sedentary adults.

Increasing the physical activity of typically sedentary adult populations is at the forefront of the public health agenda. This review addresses the challenges in defining and measuring physical activity in this target group, for a number of purposes, namely, scientific or academic inquiry, surveillance, clinical application and programme evaluation. First, we clarify the conceptual distinctions between the terms sedentarism, physical inactivity, physical activity and energy expenditure. Next, we review and compare the utility of different approaches for quantifying and expressing physical activity in these populations. Physical activity in typically sedentary populations is most likely a simple pattern of behaviour that has been largely obscured by existing measures and its expression as energy expenditure. Existing self-report methods are practical, but suffer from floor effects and recall bias. Walking, the most important activity to assess in this target group, is very difficult to measure through self-report methods. Motion sensors are more appropriate for quantifying physical activity behaviours in typically sedentary populations. Of the 2 types of motion sensors - the accelerometer and the pedometers--the latter is more appealing because it is both an affordable and a 'good enough' measure of physical activity, specifically ambulatory activity. Although a common measurement approach would greatly facilitate our understanding of physical activity behaviour patterns, the selection of an approach ultimately depends on the purpose of the study and to a great extent, its budget. Researchers, clinicians and practitioners interested in accurately capturing the lower end of the continuum of physical activity (that is characteristic of sedentary populations) must thoughtfully consider the relative advantages and disadvantages of the available approaches.

Adult↗

Purification and characterization of soluble starch synthases from maize endosperm.

This study identified and characterized the soluble starch synthase of maize endosperm that was initially revealed as the SSII activity peak in anion exchange chromatography (J. L. Ozbun et al. (1971) Plant Physiol. 48, 765-769). At least six different genes coding for starch synthases are expressed in maize, although previously it was not known which of these is responsible for the SSII activity peak. The enzyme activity in the SSII peak was neutralized to a large extent by antibodies raised against the product of the Du1 gene, but was not affected by antibodies specific for the other highly expressed soluble starch synthase, zSSI, or for the zSSIIa or zSSIIb isoforms. These data provide direct evidence that Du1 codes for the starch synthase responsible for the SSII activity peak. This starch synthase was purified approximately 350-fold from endosperm extracts. The following enzymatic properties of the SSII activity were determined: temperature optimum, thermostability, pH effects, K(m) for different glucan primers and the glucosyl unit donor ADPGlc, V(max) using various primers, and stimulation by citrate. These properties were compared to those of zSSI purified over 1600-fold from maize endosperm by a parallel procedure. The major differences between the two enzymes were that the SSII activity displayed higher K(m) values for ADPGlc, a distinct temperature range for maximal activity, and different relative activities toward specific exogenous substrates. The purified SSI and SSII activities both were shown to be capable of elongating maltooligosaccharide primers in vitro.

Enzyme Stability↗

Depletion of CD34+ CD4+ cells in bone marrow from HIV-1-infected individuals.

Pancytopenia as a consequence of bone marrow abnormalities is commonly seen in HIV-infected individuals. To examine the effect that HIV-1 has on hematopoietic cells, we compared hematopoietic properties of bone marrow samples from HTV+ patients at various stages of disease with bone marrow samples from uninfected donors. While the absolute number of recovered CD34+ cells and the cloning efficiency of these cells did not differ significantly in HIV+ donors, the percentage of CD34+ CD4+ cells was significantly depleted in late-stage HIV+ patients. We observed a direct correlation between the numbers of CD34+ CD4+ cells in the bone marrow and the peripheral CD4 count. Further characterization of the CD34+ CD4+ subpopulation demonstrated that these cells expressed lower levels of HLA-DR on their surface compared with CD34+ CD4- cells, suggesting an immature phenotype. We also found evidence for expression of HIV-1 coreceptors CXCR-4 and CKR-5 message and protein in CD34+ bone marrow cells. While this finding suggested that hematopoietic cells might be susceptible to HIV infection at an early stage of maturation, thus affecting different cell lineages as they matured, we did not find any evidence for infection of HIV in these cells. These data suggest that HIV affects early hematopoietic progenitor cells either directly or indirectly, and in particular CD34+ CD4+ cells. This finding has important implications for disease pathogenesis and for application of gene therapy approaches that use CD34+ hematopoietic cells.

Acquired Immunodeficiency Syndrome↗

A randomized outcome evaluation of group exercise programs in long-term care institutions.

BACKGROUND: Physical activity programs in nursing homes typically consist of seated, range of motion (ROM) exercises, regardless of resident abilities. The Functional Fitness for Long-Term Care (FFLTC) Program was designed not only to maintain ROM, but also to improve strength, balance, flexibility, mobility, and function. In addition, it was tailored to meet the needs of both high and low mobility residents. METHODS: The feasibility and efficacy of the FFLTC Program were evaluated with 68 residents (mean age 80) from five institutions. Persons were classified as low or high mobility and randomized into either the FFLTC program or a seated ROM program. Classes were conducted in groups of 4 to 10 residents by trained facility staff for 45 minutes, three times per week. Assessments at baseline and 4 months consisted of mobility, balance, gait, flexibility, functional capacity, and several upper and lower extremity strength measures. RESULTS: Attendance averaged 86% for the FFLTC and 79% for the ROM classes. Four months of exercise led to significant improvements in mobility (16%), balance (9%), flexibility (36%), knee (55%), and hip (12%) strength for the FFLTC group. Shoulder strength was the only improvement found for the ROM group. The ROM group significantly deteriorated in some areas, particularly hip strength, mobility, and functional ability. CONCLUSIONS: Institutionalized seniors, even those who are physically frail, incontinent and/or have mild dementia, can respond positively to a challenging exercise program. The FFLTC program demonstrated clear benefits over typical, seated ROM exercises. Moreover, with minimal training, the program can be safely delivered at low cost by institutional staff and volunteers.

Activities of Daily Living↗

An individualized approach to outcome measurement in geriatric rehabilitation.

BACKGROUND: The heterogeneity of health problems experienced by frail elderly patients makes it difficult to use a single standard measure to evaluate multiple outcomes of geriatric rehabilitation. Commonly, several measures are used, but an alternative is to use an individualized measure such as Goal Attainment Scaling (GAS). This study investigated the reliability, validity, and responsiveness of GAS as an outcome measure in geriatric rehabilitation. METHODS: We studied 173 consecutive admissions (mean age 81; 77% female; mean length of stay 33 days) to a geriatric rehabilitation unit. Assessment instruments were completed at admission and discharge. Individualized treatment goals were identified for each patient by using GAS; standardized measures included self-rated health, a global clinical assessment, the Barthel Index, the OARS IADL scale, the Folstein Mini-Mental State Examination (MMSE), and the Nottingham Health Profile (NHP). RESULTS: Mobility, future care arrangements, and functional impairment were the most commonly identified GAS goal areas. The interrater reliability of the GAS discharge score was 0.93. The GAS discharge score correlated strongly (r> or =0.50) with the standardized measures, except for self-rated health, the MMSE, and the NHP (r> or =0.31). GAS was more responsive to change than any of the standardized measures. The GAS score was used to derive receiver operating characteristic curves for other measures; this can provide insight into the interpretation of clinically important outcomes. CONCLUSIONS: GAS appears to be a feasible, reliable, valid, and responsive approach to outcome measurement in geriatric rehabilitation.

Activities of Daily Living↗

Measuring accumulated health-related benefits of exercise participation for older adults: the Vitality Plus Scale.

BACKGROUND: Existing measures fail to capture the perceived benefits attributed to exercise participation by older adults themselves. Noticeable improvements in sleep, energy level, bodily aches and pains, constipation, and other psychophysical aspects of "feeling good" may represent ongoing sources of motivation for continued participation. The Vitality Plus Scale (VPS) was developed to measure these potential health-related benefits of exercising. METHODS: The 10-item VPS was developed using an inductive approach, in collaboration with regularly exercising older adults and their instructors. Multiple samples of exercises and nonexercisers ranging in age from 40 to 94 were used to examine the reliability and validity of the new scale. RESULTS: The VPS showed good internal consistency and test-retest reliability over one week. Scores were able to discriminate on the basis of various indicators of health status and self-reported level of physical activity, and were related to two measures of functional mobility. Convergence was found with several subscales of the SF-36, whereas low correlations emerged with a measure of episode-specific sensations. Responsiveness to change was found with various types of exercise for individuals with low to moderate scores prior to participation. CONCLUSIONS: Improvements in sleep, energy level, mood, and generally feeling good appear to be the most noticeable benefits of exercising for many adults. These associations are reinforced by sustained exercise participation. Capturing these interrelated psychophysical constructs in a single, short measure will enable exercise researchers and instructors to measure incremental improvements previously reported only anecdotally.

Adult↗

Purification and molecular genetic characterization of ZPU1, a pullulanase-type starch-debranching enzyme from maize.

This study identified and purified specific isoamylase- and pullulanase-type starch-debranching enzymes (DBEs) present in developing maize (Zea mays L.) endosperm. The cDNA clone Zpu1 was isolated based on its homology with a rice (Oryza sativa L.) cDNA coding for a pullulanase-type DBE. Comparison of the protein product, ZPU1, with 18 other DBEs identified motifs common to both isoamylase- and pullulanase-type enzymes, as well as class-specific sequence blocks. Hybridization of Zpu1 to genomic DNA defined a single-copy gene, zpu1, located on chromosome 2. Zpu1 mRNA was abundant in endosperm throughout starch biosynthesis, but was not detected in the leaf or the root. Anti-ZPU1 antiserum specifically recognized the approximately 100-kD ZPU1 protein in developing endosperm, but not in leaves. Pullulanase- and isoamylase-type DBEs were purified from extracts of developing maize kernels. The pullulanase-type activity was identified as ZPU1 and the isoamylase-type activity as SU1. Mutations of the sugary1 (su1) gene are known to cause deficiencies of SU1 isoamylase and a pullulanase-type DBE. ZPU1 activity, protein level, and electrophoretic mobility were altered in su1-mutant kernels, indicating that it is the affected pullulanase-type DBE. The Zpu1 transcript levels were equivalent in nonmutant and su1-mutant kernels, suggesting that coordinated regulation of ZPU1 and SU1 occurs posttranscriptionally.

Amino Acid Sequence↗

Identification of the soluble starch synthase activities of maize endosperm.

This study identified the complement of soluble starch synthases (SSs) present in developing maize (Zea mays) endosperm. The product of the du1 gene, DU1, was shown to be one of the two major soluble SSs. The C-terminal 450 residues of DU1 comprise eight sequence blocks conserved in 28 known or predicted glucan synthases. This region of DU1 was expressed in Escherichia coli and shown to possess SS activity. DU1-specific antisera detected a soluble endosperm protein of more than 200 kD that was lacking in du1- mutants. These antisera eliminated 20% to 30% of the soluble SS activity from kernel extracts. Antiserum against the isozyme zSSI eliminated approximately 60% of the total soluble SS, and immunodepletion of du1- mutant extracts with this antiserum nearly eliminated SS activity. Two soluble SS activities were identified by electrophoretic fractionation, each of which correlated specifically with zSSI or DU1. Thus, DU1 and zSSI accounted for the great majority of soluble SS activity present in developing endosperm. The relative activity of the two isozymes did not change significantly during the starch biosynthetic period. DU1 and zSSI may be interdependent, because mutant extracts lacking DU1 exhibited a significant stimulation of the remaining SS activity.

Amino Acid Sequence↗

Control of Saccharomyces cerevisiae filamentous growth by cyclin-dependent kinase Cdc28.

The ascomycete Saccharomyces cerevisiae exhibits alternative vegetative growth states referred to as the yeast form and the filamentous form, and it switches between the two morphologies depending on specific environmental signals. To identify molecules involved in control of morphologic differentiation, this study characterized mutant S. cerevisiae strains that exhibit filamentous growth in the absence of the normal external signals. A specific amino acid substitution in the cyclin-dependent protein kinase Cdc28 was found to cause constitutive expression of most filamentous growth characteristics. These effects include specifically modified cell polarity characteristics in addition to the defined shape and division cycle alterations typical of the filamentous form. Several other mutations affecting Cdc28 function also had specific effects on filamentous growth. Constitutive filamentous growth resulting from deletion of the protein kinase Elm1 was prevented by modification of Cdc28 such that it could not be phosphorylated on tyrosine residue 19. In addition, various mutations affecting Hsl1 or Swe1, known or presumed components of a protein kinase cascade that mediates Cdc28 phosphorylation on Y19, either prevented or enhanced filamentous growth. The data suggest that a protein kinase cascade involving Elm1, Hsl1, and Swe1 can modulate Cdc28 activity and that Cdc28 in turn exerts global effects that cause filamentous growth.

CDC28 Protein Kinase, S cerevisiae↗

Clinical experience with Goal Attainment Scaling in geriatric care.

OBJECTIVES: This article presents a qualitative evaluation of the utility of Goal Attainment Scaling (GAS) in geriatric care. GAS is an individualized outcome measure particularly suited for clients with multiple complex problems, such as are commonly served by geriatric programs. METHODS: Semistructured interviews were completed with 24 clinicians in four hospital or community-based geriatric services where GAS has been used. An inductive analysis was used to identify themes. RESULTS: GAS was described as resulting in shorter lengths of stay, more focused care, and improved team functioning. GAS was perceived as having greater use for functional (versus medical) goals, when clinicians had more direct control over treatments, when patients were involved in goal-setting, and when goals were set by an interdisciplinary team. DISCUSSION: GAS has affected both care practices and patient outcomes. This study illustrates the clinical impacts an outcome measure can have, as well as the use of qualitative methods for this type of research.

Aged↗