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Biomedical subjects

C Levenson

Publications and source records attributed to C Levenson.

18 recordsLinked to original sources

Exercise--it's never too late: the strong-for-life program.

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.

Aged↗

Home-based resistance training: predictors of participation and adherence.

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.

Aged↗

A home-based exercise program for nondisabled older adults.

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.

Affect↗

Physicochemical studies of the d(G3T4G3)*d(G3A4G3).d(C3T4C3) triple helix.

We have targeted the d(G3A4G3).d(C3T4C3) duplex for triplex formation with d(G3T4G3) in the presence of MgCl2. The resulting triple helix, d(G3T4G3)*d(G3-A4G3).d(C3T4C3), is considerably weaker than the related triplex, d(G3A4G3)*d(G3A4G3).d(C3T4C3), and melts in a biphasic manner, with the third strand dissociating at temperatures about 20-30 degrees C below that of the remaining duplex. This is in distinct contrast to the d(G3A4G3)*d(G3A4G3).d(C3T4C3) triplex, which melts in essentially a single transition. Gel electrophoresis under non-denaturing conditions shows the presence of the d(G3T4G3)*d(G3A4G3).d(C3T4C3) triplex as a band of low mobility compared to the duplex or the single strand bands. Binding of the d(G3T4G3) third strand and the purine strand of the duplex can be monitored by imino proton NMR spectra. While these spectra are typically very broad for intermolecular triplexes, the line widths can be dramatically narrowed by the addition of two thymines to both ends of the pyrimidine strand. Thermodynamic analysis of UV melting curves shows that this triplex is considerably less stable than related triplexes formed with the same duplex. The orientation of the third strand was addressed by a combination of fluorescence energy transfer and UV melting experiments. Results from these experiments suggest that, in the unlabeled triplex, the preferred orientation of the third strand is parallel to the purine strand of the duplex.

Base Sequence↗

NMR investigation of the interaction of mithramycin A with d(ACCCGGGT)2.

The binding of mithramycin A to d(ACCCGGGT)2 has been investigated by one- and two-dimensional 1H NMR spectroscopy. Titration of the drug into the octamer solution results in loss of the oligonucleotide C2 symmetry at stoichiometric ratios less than 4 drug molecules per duplex. However, at a ratio of 4:1 (drug/duplex), the C2 symmetry of the oligonucleotide is restored. From these data it is evident that more than one complex forms at ratios less than 4:1 while only one complex predominates at the ratio 4:1. This is the first report of a DNA octamer which binds 4 large drug molecules. These results are compared to those we have recently reported for mithramycin binding to d(ATGCAT)2, where only a single, bound complex is observed, with a stoichiometry of 2:1.

Base Sequence↗

Structure, stability, and thermodynamics of a short intermolecular purine-purine-pyrimidine triple helix.

We have investigated the structure and physical chemistry of the d(C3T4C3).2[d(G3A4G3)] triple helix by polyacrylamide gel electrophoresis (PAGE), 1H NMR, and ultraviolet (UV) absorption spectroscopy. The triplex was stabilized with MgCl2 at neutral pH. PAGE studies verify the stoichiometry of the strands comprising the triplex and indicate that the orientation of the third strand in purine-purine-pyrimidine (pur-pur-pyr) triplexes is antiparallel with respect to the purine strand of the underlying duplex. Imino proton NMR spectra provide evidence for the existence of new purine-purine (pur.pur) hydrogen bonds, in addition to those of the Watson-Crick (W-C) base pairs, in the triplex structure. These new hydrogen bonds are likely to correspond to the interaction between third-strand guanine NH1 imino protons and the N7 atoms of guanine residues on the purine strand of the underlying duplex. Thermal denaturation of the triplex proceeds to single strands in one step, under the conditions used in this study. Binding of the third strand appears to enhance the thermal stability of the duplex by 1-3 degrees C, depending on the DNA concentration. The free energy of triplex formation (-26.0 +/- 0.5 kcal/mol) is approximately twice that of duplex formation (-12.6 +/- 0.7 kcal/mol), suggesting that the overall stability of the pur.pur base pairs is similar to that of the W-C base pairs.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Composition↗

Effects of primer-template mismatches on the polymerase chain reaction: human immunodeficiency virus type 1 model studies.

We investigated the effects of various primer-template mismatches on DNA amplification of an HIV-1 gag region by the polymerase chain reaction (PCR). Single internal mismatches had no significant effect on PCR product yield while those at the 3'-terminal base had varied effects. A:G, G:A, and C:C mismatches reduced overall PCR product yield about 100-fold, A:A mismatches about 20-fold. All other 3'-terminal mismatches were efficiently amplified, although the G:G mismatches appeared to be more sensitive to sequence context and dNTP concentrations than other mismatches. It should be noted that mismatches of T with either G, C, or T had a minimal effect on PCR product yield. Double mismatches within the last four bases of a primer-template duplex where one of the mismatches is at the 3' terminal nucleotide, in general, reduced PCR product yield dramatically. The presence of a mismatched T at the 3'-terminus, however, allowed significant amplification even when coupled with an adjacent mismatch. Furthermore, even two mismatched Ts at the 3'-terminus allowed efficient amplification.

Base Composition↗

Structural analysis of the (dA)10.2(dT)10 triple helix.

The existence of DNA triple helices in vitro has been known for some time. Recent evidence suggesting that DNA triplexes exist in vivo and showing their potential for chemotherapeutic applications has renewed interest in these triple-strand conformations. However, little structural information is currently known about these unusual nucleic acid forms. We have induced and stabilized triple-helical (dA)10.2(dT)10 with MgCl2 at neutral pH. UV mixing curves demonstrate a 1:2 (dA)10 to (dT)10 stoichiometry at suitable MgCl2 concentrations. Thermal denaturation profiles establish a melting mechanism characterized by the initial loss of the third strand, followed by dissociation of the remaining duplex. The circular dichroic spectrum of the triplex form is distinct from that of a duplex equimolar in (dA)10. NMR studies show that magnesium-induced triplex formation is accompanied by an upfield shift of several imino proton resonances present before stabilization of the triplex form with MgCl2 and the induction of new upfield imino proton resonances. Nuclear Overhauser effect spectroscopy measurements on both undeuterated and C8--H-deuterated (dA)10.2(dT)10 triplexes demonstrate dipolar contacts between resolvable imino proteins and both adenine C8--H and C2--H aromatic protons. Hence, MgCl2 stabilizes a triplex structure in which thymine N3--H imino protons are involved in both Watson-Crick and Hoogsteen base pairing.

Base Composition↗

The conformation of the d(ACCCGGGT) duplex in aqueous solution.

The nonexchangeable base and sugar protons of the octanucleotide d(ACCCGGGT)2 have been assigned using two dimensional homonuclear Hartmann-Hahn relayed spectroscopy (HOHAHA), double quantum filtered homonuclear correlation spectroscopy (DQFCOSY) and nuclear Overhauser spectroscopy (NOESY) in D2O at 12 degrees C. The observed NOE's between the base protons and their own H2' protons and between the base protons and the H2' protons of the 5' adjacent nucleotide and the observed coupling constants between the deoxyribose 1' and 2',2'' protons indicate that this duplex assumes a right-handed B-type helix conformation in solution.

Magnetic Resonance Spectroscopy↗

Nonisotopic M13 probes for detecting the beta-globin gene: application to diagnosis of sickle cell anemia.

M13 DNA probes labeled with biotinylated psoralen and a streptavidin-horseradish peroxidase conjugate provide nonradioactive detection of the sickle cell and normal alleles of the beta-globin locus. The two biotinylated probes contain single-stranded sequences complementary to two different Sau3AI restriction fragments from the 5' region of the beta-globin gene and double-stranded M13 vector sequences. These probes are labeled with biotinylated psoralen photochemically linked to DNA. After hybridization, the presence of biotinylated probe bound to target DNA is detected in 3 h by using a streptavidin-horseradish peroxidase conjugate and the substrate, 3,3',5,5'-tetramethylbenzidine. Digestion of the normal (beta A) allele of the beta-globin gene with MstII (or isoschizomers) yields a 1.14-kb restriction fragment, while digestion of the mutant beta S allele yields a 1.34-kb fragment. These fragments can be resolved by gel electrophoresis and detected by Southern blot hybridization. The nonradioisotopic probe system can detect the beta-globin restriction fragment in as little as 0.5 microgram of human DNA and can distinguish heterozygotes (beta A beta S) from homozygotes (beta A beta A or beta S beta S) in 2.0 micrograms of human DNA.

Alleles↗

Genetic and biochemical analysis of ras p21 structure.

We tested aspects of our model of the ras p21 structure using generic, biochemical, and immunologic approaches. First, we made a monoclonal antibody against a p21 region that is highly conserved and likely to be critical to p21 function. The antibody blocks p21 function in various cell systems. Its binding to p21 is completely blocked by guanine nucleotides, even though the region of p21 to which it binds does not seem to be part of the guanine nucleotide-binding site. We propose that the conformation of this critical region is modulated by nucleotide binding. Another interesting region of p21 includes amino acids 116 and 119, which seem to confer, in part, the specificity of p21 for guanine nucleotides. We made a series of mutants in this region and tested their ability to bind GTP, and such related purine nucleotides as XTP and diaminopurine nucleoside triphosphate. We were able to refine our model for guanine nucleotide interaction with p21 and to create mutant proteins with altered specificity for purine nucleotides. Finally, we tested rates of autophosphorylation of six position 12 mutants and conclude that amino acid 12 affects the positioning of bound nucleotides relative to sequences around amino acid 59.

Genes, ras↗

Aqueous solution structure of an intercalated actinomycin D-dATGCAT complex by two-dimensional and one-dimensional proton NMR.

Two-dimensional NOESY and COSY 1H NMR techniques have been employed to determine the conformation of the complex formed by actinomycin D and the hexanucleoside pentaphosphate dATGCAT. One-dimensional NOE experiments in H2O confirmed the intact nature of the oligonucleotide double helix within the complex. The drug chromophore was intercalated between the GC base pairs, with the pentapeptide lactones nestled in the minor groove. No significant conformational change of the pentapeptide lactones between bound and free drug was observed.

Dactinomycin↗

An evaluation of I Can Cope. Insights into program design and implementation.

The I Can Cope program is an educational program developed to provide information on how to promote physical and emotional well-being to individuals with cancer, their families, and friends. Through focus group and individual interviews and a mailed survey, the effectiveness of the selection, marketing, implementation, and support processes associated with implementing the program in the central Arizona and greater Las Vegas, Nevada, regions was evaluated. Findings, recommendations, lessons learned, and use of findings are discussed.

Adaptation, Psychological↗

Preventing postoperative burn wound aspergillosis.

Between January 1, 1984, and December 31, 1988, 35 patients at the Los Angeles County + University of Southern California Burn Center had postoperative cultures from their burn wounds that grew Aspergillus species; clinical burn-wound aspergillosis occurred in 66% of these cases and death occurred in 53% of these cases. Beginning in November 1984, several modifications in the air-conditioning system and topical antimicrobial wound therapy were undertaken. Cleaning and 8Cu-quinolinolate treatment of air ducts every 2 months did not reliably clear Aspergillus species from the air in patient care areas. Several changes in topical therapeutic regimen failed to prevent both burn wound culture positivity and clinical aspergillosis. Finally, installation of high-efficiency particulate air filters, installation of new air ducts, and inception of wound irrigation with a solution of mafenide hydrochloride plus nystatin both during and after operation were associated with a reduction in wound culture positivity rate to one occurrence in 1988 (Poisson probability less than 0.01 versus the rate in 1984) and no occurrences during the 18 months after the false ceiling of the burn ward was sealed.

Aspergillosis↗