Two illnesses.
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Biomedical subjects
Publications and source records attributed to B A Harris.
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Regulators of G protein signaling (RGS) proteins that contain DEP (disheveled, EGL-10, pleckstrin) and GGL (G protein gamma subunit-like) domains form a subfamily that includes the mammalian RGS proteins RGS6, RGS7, RGS9, and RGS11. We describe the cloning of RGS6 cDNA, the specificity of interaction of RGS6 and RGS7 with G protein beta subunits, and certain biochemical properties of RGS6/beta5 and RGS7/beta5 complexes. After expression in Sf9 cells, complexes of both RGS6 and RGS7 with the Gbeta5 subunit (but not Gbetas 1-4) are found in the cytosol. When purified, these complexes are similar to RGS11/beta5 in that they act as GTPase-activating proteins specifically toward Galpha(o). Unlike conventional G(betagamma) complexes, RGS6/beta5 and RGS7/beta5 do not form heterotrimeric complexes with either Galpha(o)-GDP or Galpha(q)-GDP. Neither RGS6/beta5 nor RGS7/beta5 altered the activity of adenylyl cyclases types I, II, or V, nor were they able to activate either phospholipase C-beta1 or -beta2. However, the RGS/beta5 complexes inhibited beta(1)gamma(2)-mediated activation of phospholipase C-beta2. RGS/beta5 complexes may contribute to the selectivity of signal transduction initiated by receptors coupled to G(i) and G(o) by binding to phospholipase C and stimulating the GTPase activity of Galpha(o).
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Several measures of dynamic stability during two functional activities correlated to quadriceps femoris muscle strength. A total of 34 disabled elders (aged 60-88) living in the Boston area consented to maximum isometric quadriceps muscle strength testing, chair rise and gait analysis. During chair rise, quadriceps strength significantly correlated with maximum upper body vertical linear momentum, r=0.53, P<0.005, anterior posterior linear momentum, r=0. 38, P<0.05, and the time to complete the chair rise, r=-0.48, P<0.05, n=29. Stride length and gait velocity correlated (r=0.56, P<0.001 and r=0.51, P<0.002, n=34) with quadriceps muscle strength. The maximum range of whole body anteroposterior (A/P) linear momentum during gait also correlated with quadriceps strength (r=0.47, P=0. 004, n=31). Dynamic stability during chair rise and gait, at preferred speed, correlates directly with quadriceps femoris muscle strength in functionally limited elderly individuals. In our sample, elders performed one of three movement strategies to arise from a chair, and quadriceps strength did not statistically differ between the chair rise strategy groups. However, persons with the greatest quadriceps strength values were more stable regardless of which chair rise strategy they performed. Our data indicate that clinicians should not suggest that patients use compensatory momentum inducing locomotor strategies unless the patient has sufficient strength to control these induced forces.
OBJECTIVES: This investigation determined whether an in-home resistance training program achieved health benefits in older adults with disabilities. METHODS: A randomized controlled trial compared the effects of assigning 215 older persons to either a home-based resistance exercise training group or a waiting list control group. Assessments were conducted at baseline and at 3 and 6 months following randomization. The program consisted of videotaped exercise routines performed with elastic bands of varying thickness. RESULTS: High rates of exercise adherence were achieved, with 89% of the recommended exercise sessions performed over 6 months. Relative to controls, subjects who participated in the program achieved statistically significant lower extremity strength improvements of 6% to 12%, a 20% improvement in tandem gait, and a 15% to 18% reduction in physical and overall disability at the 6-month follow-up. No adverse health effects were encountered. CONCLUSIONS: These findings provide important evidence that home-based resistance exercise programs designed for older persons with disabilities hold promise as an effective public health strategy.
The crystal structure of human endostatin reveals a zinc-binding site. Atomic absorption spectroscopy indicates that zinc is a constituent of both human and murine endostatin in solution. The human endostatin zinc site is formed by three histidines at the N terminus, residues 1, 3, and, 11, and an aspartic acid at residue 76. The N-terminal loop ordered around the zinc makes a dimeric contact in human endostatin crystals. The location of the zinc site at the amino terminus, immediately adjacent to the precursor cleavage site, suggests the possibility that the zinc may be involved in activation of the antiangiogenic activity following cleavage from the inactive collagen XVIII precursor or in the cleavage process itself.
BACKGROUND AND PURPOSE: Simple, practical and reliable clinical balance outcome measures are needed to assess baseline status and response to treatment in older people. The reliability of the clinical measures used in this testing protocol had not been determined for this population. This study assessed the inter-rater reliability of three commonly used clinical measures of balance: one leg standing, tandem gait and functional reach. METHOD: Two samples of older people were used: (1) non-disabled and (2) disabled community dwellers. All testing was performed in a single session by two trained examiners according to a standardized protocol. Intra-class correlations were calculated comparing the means of each clinical balance test for Examiner 1 with Examiner 2. RESULTS: Reliability coefficients were 0.75 for one leg standing, 0.73 for functional reach, and 0.31 for tandem gait for the non-disabled sample. Reliability coefficients were 0.85 for one leg standing, 0.79 for functional reach, and 0.62 for tandem gait for the disabled sample. CONCLUSIONS: These findings for the one leg standing and functional reach testing protocols in disabled and non-disabled older people can be used as outcome measures. Further study should be directed towards improving the reliability of the tandem gait test for use with older people.
The presence of topological knots in large RNA structures is highly unlikely given that 1) no RNA structures determined thus far contain topological knots, 2) secondary structure maps for most RNA molecules are knot free, 3) there are no known RNA topoisomerases, and 4) it is difficult to imagine how knots could be formed specifically and uniquely during transcription. Since native RNA structures probably lack topological knots, models of these RNA molecules should be free of knots as well. Therefore, we have examined four existing models for the 30S ribosomal subunit to determine if any of the three domains of the 16S rRNA molecule is knotted. We found that all but one model had at least one knotted domain. We conclude that models of large RNA molecules should be examined for knotting before publication.
BACKGROUND: Understanding interrelationships among disablement concepts is critical to the design of future disability treatment and prevention interventions. METHODS: This study uses cross-sectional data to examine the relationships among physiologic impairments, functional limitations, and disability in a moderately disabled sample of 207 community-dwelling older adults. RESULTS: As hypothesized, the data revealed statistically significant curvilinear relationships of upper and lower extremity strength and balance with mobility in this older sample. Multivariate analyses further clarified the hypothesized causal mechanism among the disablement concepts by demonstrating that most of the association of muscle strength and balance with disability was through the intermediary role of mobility limitations. CONCLUSIONS: The findings from this study highlight the value of clinical trials that focus on prevention or treatment of mobility limitations as a means of preventing disability; our findings underscore the need for future research that examines the effects of other variables believed to influence disablement in late life.
This study identified factors associated with exercise participation and adherence in a sample of 102 sedentary, functionally limited, community-dwelling adults aged 60 to 94 years who participated in a home-based resistance training program. Stepwise regression analyses revealed that baseline physical factors (i.e., higher levels of mobility, weaker muscle strength, and fewer numbers of new medical conditions) were associated with higher rates of participation in the home program. Positive attitudes and a sense of control toward exercise, lower levels of confusion and depressive moods, and the development of fewer new medical problems during the program were related to higher levels of adherence to the program. Findings revealed that although physical health variables were the primary indicators of an older person's overall participation in the program, it was the psychological factors that were most important to adherence to this home-based program.
Space Medicine is a discipline whose scope will encompass primary and advanced medical care amidst the environmental constraints of space. At one time, there was a Department of Space Medicine associated with the U.S. Air Force School of Aviation Medicine. Until 1993, an academic, university-based training program dedicated to space medicine did not exist. This paper reviews the history of space medicine in the United States. It presents the current conceptions of space medicine, and postulates the need for space medicine to mature as a distinct discipline.
OBJECTIVE: To examine in vivo maximum acetabular contact pressures during gait and hip arthritis exercises recommended by clinicians and the Arthritis Foundation. METHODS: Acetabular contact pressure data were collected for 2.5 years, at 3-4-month intervals, from an instrumented endoprosthesis implanted in an 84-year-old male who had sustained a left hip fracture. Maximum pressure data were compared for each activity. RESULTS: Mean pressures ranged from 9.0 +/- 2.3 megapascals (MPa) during maximum isometric hip abduction, 9.0 +/- 0.8 MPa during standing right hip abduction, and 8.9 +/- 2.8 MPa during standing left hip abduction to 1.2 +/- 0.3 MPa during quiet standing. Free-speed gait pressure averaged 5.6 +/- 0.9 MPa. The maximum mean pressure during side-lying hip abduction and straight leg raise at 30 degrees/second were less than the same activities at 60 degrees/second. CONCLUSIONS: These in vivo hip pressure measurements challenge traditional protocols for patients with hip osteoarthritis and provide quantitative data as a framework for designing exercise programs. Maximum isometric hip exercise and standing exercise generated much higher hip pressures, and are therefore probably more stressful to acetabular cartilage, than gait or stationary cycling. Clinicians must consider exercise velocity because of its direct correlation with hip contact pressure. Walking generated lower pressure than most activities studied and, given its other benefits, is therefore probably beneficial for patients with hip osteoarthritis.
BACKGROUND AND PURPOSE: The purposes of this study were (1) to describe the demographic and clinical characteristics of a group of patients with acute low back pain (LBP), (2) to describe those patients who were being treated by physical therapists, and (3) to analyze their use of physical therapy services. SUBJECTS: The study sample consisted of 1,580 patients with acute LBP who were treated by 208 practitioners in North Carolina. The initial providers were primary care physicians, chiropractors, orthopedic surgeons, and primary care providers at a health maintenance organization. METHODS: A telephone interview was conducted after the initial office visit to assess demographics and medical history, health care services utilization, and functional status. Follow-up telephone interviews were also conducted 2, 4, 8, 12, and 24 weeks later. RESULTS: One hundred ninety-nine (12.6%) of the subjects reported that they saw a physical therapist either by any provider referral or by direct access. Therapeutic exercise was the most commonly reported treatment procedure. Post-high-school education, receipt of Workers' Compensation, prior physical therapy for LBP, LBP and pain below the knee in one or both legs, and a higher baseline Roland-Morris Questionnaire score were associated with being treated by physical therapists. CONCLUSION AND DISCUSSION: In this study, physical therapists were utilized in the treatment of patients with greater severity of LBP. The findings demonstrate the importance of controlling for baseline characteristics when comparing outcomes of LBP when treated by different types of providers.
OBJECTIVE: To develop techniques for conducting a physical examination in microgravity and to describe and document the physiologic changes noted with use of a modified basic physical examination. DESIGN: On the basis of data gathered from physical examinations on KC-135 flights, three physical variables were assessed serially in astronauts during two shuttle missions (of 8- and 10-day duration, respectively). Preflight, in-flight, and postflight examinations were conducted by trained physician-astronauts or flight surgeons, who used this modified examination. MATERIAL AND METHODS: Five male and two female crewmembers participated in the "hands-on" physical examination of all physiologic systems except the genitourinary system. Level of edema, intensity of bowel sounds, and peripheral reflexes were assessed and graded. RESULTS: This investigation identified unique elements of a physical examination performed during space flight that will assist in the development of standard methods for conducting examinations of astronauts in weightlessness. In addition, demonstrable changes induced by microgravity were noted in most physiologic systems examined. CONCLUSION: The data support the hypothesis that the microgravity examination differs from that conducted on earth or in a 1g environment. In addition, alterations in the physiologic response can be detected with use of hands-on technique. These data are invaluable in the development of optimal medical care for humans in space.
OBJECTIVES: This paper describes a videotaped, home-based, strength training program, titled Strong-for-Life and reports on its effectiveness in improving muscle strength, psychological well-being, and health status in a sample of older persons. DESIGN AND SETTING: We enrolled 102 nondisabled, community-dwelling older people aged 66 to 87, identified from the Medicare beneficiary list, into a randomized, controlled trial. MEASUREMENTS: Effectiveness was based on change in isokinetic upper and lower extremity muscle strength, psychologic well-being, and health status. RESULTS: Results revealed several statistically significant short-term benefits after 12 to 15 weeks of exercise, especially for men. Younger older adults demonstrated a 10% improvement in knee extensor strength relative to control subjects. Older male exercisers achieved significant differences relative to controls in perceived anger, tension, and overall social functioning. Male exercisers, in general, achieved significant improvement in perceived vigor. Women did not report psychological benefits following participation in the program. CONCLUSION: Study results reveal that the Strong for Life program, designed to be widely disseminated to the nondisabled older population, has many short-term positive benefits.
The crystal structure of the reverse transcriptase (RT) from the type 1 human immunodeficiency virus has been determined at 3.2-A resolution. Comparison with complexes between RT and the polymerase inhibitor Nevirapine [Kohlstaedt, L.A., Wang, J., Friedman, J.M., Rice, P.A. & Steitz, T.A. (1992) Science 256, 1783-1790] and between RT and an oligonucleotide [Jacobo-Molina, A., Ding, J., Nanni, R., Clark, A. D., Lu, X., Tantillo, C., Williams, R. L., Kamer, G., Ferris, A. L., Clark, P., Hizi, A., Hughes, S. H. & Arnold, E. (1993) Proc. Natl. Acad. Sci. USA 90, 6320-6324] reveals changes associated with ligand binding. The enzyme is a heterodimer (p66/p51), with domains labeled "fingers," "thumb," "palm," and "connection" in both subunits, and a ribonuclease H domain in the larger subunit only. The most striking difference between RT and both complex structures is the change in orientation of the p66 thumb (approximately 33 degrees rotation). Smaller shifts relative to the core of the molecule were also found in other domains, including the p66 fingers and palm, which contain the polymerase active site. Within the polymerase catalytic region itself, there are no rearrangements between RT and the RT/DNA complex. In RT/Nevirapine, the drug binds in the p66 palm near the polymerase active site, a region that is well-packed hydrophobic core in the unliganded enzyme. Room for the drug is provided by movement of a small beta-sheet within the palm domain of the Nevirapine complex. The rearrangement within the palm and thumb, as well as domain shifts relative to the enzyme core, may prevent correct placement of the oligonucleotide substrate when the drug is bound.
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The muscarinic M2 receptor that normally couples via Gi to inhibit adenylyl cyclase was made to couple to Gs by exchange of its third intracellular loop for the comparable domain of the beta 2-adrenoceptor. In HeLa cells transfected with the recombinant M2 beta i-3 cDNA, the chimaeric receptor showed carbachol-mediated activation of adenylyl cyclase (EC50 = 73 nM) that was blocked by atropine, but not by propranolol. The chimaeric receptor was shown to mediate a carbachol-stimulated, Bordetella pertussis toxin-sensitive GTPase activity in membranes of transfected HeLa cells. Interestingly, stimulation of adenylyl cyclase by carbachol was 2-fold higher in transfected cells that had been pretreated with pertussis toxin. These data suggested that the M2 beta i-3 receptor was able to couple to both Gi and Gs, and that the ability to recognise and stimulate Gi did not involve the third cytoplasmic loop of M2. We investigated peptide elements taken from the second intracellular loop of the M2 receptor for their ability to mediate activation of Gi and found that a nine amino acid peptide representing the C-terminal sequence, VKRTTKMAG-NH2 (V9G), was capable of inhibiting forskolin-stimulated adenylyl cyclase by up to 18% and could stimulate high affinity GTPase activity of rat brain membranes by 32%. Further, V9G was shown to cause a doubling of the initial rate of [35S]GTP gamma S binding to purified bovine brain Gi/Go in reconstituted phospholipid vesicles. These data identify a domain on the second intracellular loop of the muscarinic M2 receptor that is involved in the selection of a pertussis toxin-sensitive G protein.