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Biomedical subjects

D Scharf

Publications and source records attributed to D Scharf.

13 recordsLinked to original sources
PubMed2001

Maharishi Vedic vibration technology on chronic disorders and associated quality of life.

There is a growing interest for more effective, innovative programs to address the chronic illness suffered by approximately 40 percent of the U.S. population. The purpose of this study was to evaluate the effects of a new Maharishi Vedic Medicine program-the Maharishi Vedic Vibration Technology-on the quality of life of individuals with chronic disorders. A total of 213 individuals took part in the study (mean age=48.55 years; average length of time of chronic illness=18.42 years). Results showed that over three sessions, the average self-reported improvement in chronic illness was 40.97 percent. Conditions related to neck pain improved the most (51.25%), followed by respiratory ailments (48.00%), digestive problems (46.90%), mental health, including anxiety and depression (46.34%), arthritis (41.57%), insomnia (37.38%), back pain (36.32%), headaches (35.83%), cardiovascular conditions (22.31%), and eye problems (21.19%). Findings also showed significant reductions in frequency of discomfort or pain (p<.000001), intensity of discomfort (p<.000001), and disabling effects of the discomfort in daily activity (p<.000001), in addition to overall improvement in mental health (p<.000001) and vitality (p<.000125). Possible mechanisms of action are presented.

Adolescent↗
PubMed2001

Membrane structural perturbations caused by anesthetics and nonimmobilizers: a molecular dynamics investigation.

The structural perturbations of the fully hydrated dimyristoyl-phosphatidylcholine bilayer induced by the presence of hexafluoroethane C(2F6), a "nonimmobilizer," have been examined by molecular dynamics simulations and compared with the effects produced by halothane CF3CHBrCl, an "anesthetic," on a similar bilayer (DPPC) (Koubi et al., Biophys. J. 2000. 78:800). We find that the overall structure of the lipid bilayer and the zwitterionic head-group dipole orientation undergo only a slight modification compared with the pure lipid bilayer, with virtually no change in the potential across the interface. This is in contrast to the anesthetic case in which the presence of the molecule led to a large perturbation of the electrostatic potential across to the membrane interface. Similarly, the analysis of the structural and dynamical properties of the lipid core are unchanged in the presence of the nonimmobilizer although there is a substantial increase in the microscopic viscosity for the system containing the anesthetic. These contrasting perturbations of the lipid membrane caused by those quite similarly sized molecules may explain the difference in their physiological effects as anesthetics and nonimmobilizers, respectively.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed2000

Molecular dynamics simulation of four-alpha-helix bundles that bind the anesthetic halothane.

The mutation of a single leucine residue (L38) to methionine (M) is known experimentally to significantly increase the affinity of the synthetic four-alpha-helix bundle (Aalpha(2))(2) for the anesthetic halothane. We present a molecular dynamics study of the mutant (Aalpha(2)-L38M)(2) peptide, which consists of a dimer of 62-residue U-shaped di-alpha-helical monomers assembled in an anti topology. A comparison between the simulation results and those obtained for the native (Aalpha(2))(2) peptide indicates that the overall secondary structure of the bundle is not affected by the mutation, but that the side chains within the monomers are better packed in the mutant structure. Unlike the native peptide, binding of a single halothane molecule to the hydrophobic core of (Aalpha(2)-L38M)(2) deforms the helical nature of one monomer in a region close to the mutation site. Increased exposure of the cysteine side chain to the hydrophobic core in the mutant structure leads to the enhancement of the attractive interaction between halothane and this specific residue. Since the mutated residues are located outside the hydrophobic core the observed increased affinity for halothane appears to be an indirect effect of the mutation.

Amino Acid Sequence↗
PubMed2000

Distribution of halothane in a dipalmitoylphosphatidylcholine bilayer from molecular dynamics calculations.

We report a 2-ns constant pressure molecular dynamics simulation of halothane, at a mol fraction of 50%, in the hydrated liquid crystal bilayer phase of dipalmitoylphosphatidylcholine. Halothane molecules are found to preferentially segregate to the upper part of the lipid acyl chains, with a maximum probability near the C(5) methylene groups. However, a finite probability is also observed along the tail region and across the methyl trough. Over 95% of the halothane molecules are located below the lipid carbonyl carbons, in agreement with photolabeling experiments. Halothane induces lateral expansion and a concomitant contraction in the bilayer thickness. A decrease in the acyl chain segment order parameters, S(CD), for the tail portion, and a slight increase for the upper portion compared to neat bilayers, are in agreement with several NMR studies on related systems. The decrease in S(CD) is attributed to a larger accessible volume per lipid in the tail region. Significant changes in the electric properties of the lipid bilayer result from the structural changes, which include a shift and broadening of the choline headgroup dipole (P-N) orientation distribution. Our findings reconcile apparent controversial conclusions from experiments on diverse lipid systems.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed2000

A designed four-alpha-helix bundle that binds the volatile general anesthetic halothane with high affinity.

The structural features of volatile anesthetic binding sites on proteins are being examined with the use of a defined model system consisting of a four-alpha-helix bundle scaffold with a hydrophobic core. Previous work has suggested that introducing a cavity into the hydrophobic core improves anesthetic binding affinity. The more polarizable methionine side chain was substituted for a leucine, in an attempt to enhance the dispersion forces between the ligand and the protein. The resulting bundle variant has an improved affinity (K(d) = 0.20 +/- 0.01 mM) for halothane binding, compared with the leucine-containing bundle (K(d) = 0.69 +/- 0.06 mM). Photoaffinity labeling with (14)C-halothane reveals preferential labeling of the W15 residue in both peptides, supporting the view that fluorescence quenching by bound anesthetic reports both the binding energetics and the location of the ligand in the hydrophobic core. The rates of amide hydrogen exchange were similar for the two bundles, suggesting that differences in binding affinity were not due to changes in protein stability. Binding of halothane to both four-alpha-helix bundle proteins stabilized the native folded conformations. Molecular dynamics simulations of the bundles illustrate the existence of the hydrophobic core, containing both W15 residues. These results suggest that in addition to packing defects, enhanced dispersion forces may be important in providing higher affinity anesthetic binding sites. Alternatively, the effect of the methionine substitution on halothane binding energetics may reflect either improved access to the binding site or allosteric optimization of the dimensions of the binding pocket. Finally, preferential stabilization of folded protein conformations may represent a fundamental mechanism of inhaled anesthetic action.

Amino Acid Sequence↗
PubMed1999

Molecular dynamics simulation of a synthetic four-alpha-helix bundle that binds the anesthetic halothane.

The structural features of binding sites for volatile anesthetics are examined by performing a molecular dynamics simulation study of the synthetic four-alpha-helix bundles (Aalpha2)2, which are formed by association of two 62-residue di-alpha-helical peptides. The peptide bundle (Aalpha2)2 was designed by Johansson et al. [Biochemistry 37 (1998) 1421-1429] and was shown experimentally to have a high affinity for the binding of the anesthetic halothane (CF3CBrCIH) in a hydrophobic cavity. Since (Aalpha2)2 can exhibit either the anti or syn topologies, the two distinct bundles are simulated both in the presence and in the absence of halothane. Nanosecond length molecular dynamics trajectories were generated for each system at room temperature (T = 298 K). The structural and dynamic effects of the inclusion of halothane are compared, illustrating that the structures are stable over the course of the simulation; that the (Aalpha2)2 bundles have suitable pockets that can accommodate halothane; that the halothane remains in the designed hydrophobic cavity in close proximity to the Trp residues with a preferred orientation; and that the dimensions of the peptide are perturbed by the inclusion of an anesthetic molecule.

Amino Acid Sequence↗
PubMed1998

Computer simulation study of synthetic 4-helix bundle that binds halothane.

1. The synthetic peptide H10A24 self-assembles in aqueous solution into a 4-helix bundle, which exhibits saturable binding of halothane. 2. Molecular dynamics simulation techniques have been used to study the vacuum structure of this bundle. 3. The simulation, initiated as four ideal parallel alpha-helices, resulted in a compact bundle, whose secondary structure remains predominantly alpha-helical. 4. The hydrophobic core has no apparent pocket large enough to accomodate halothane.

Algorithms↗
PubMed1998

Effects of anesthetics on the structure of a phospholipid bilayer: molecular dynamics investigation of halothane in the hydrated liquid crystal phase of dipalmitoylphosphatidylcholine.

We report the results of constant temperature and pressure molecular dynamics calculations carried out on the liquid crystal (Lalpha) phase of dipalmitoylphosphatidylcholine with a mole fraction of 6.5% halothane (2-3 MAC). The present results are compared with previous simulations for pure dipalmitoylphosphatidylcholine under the same conditions (Tu et al., 1995. Biophys. J. 69:2558-2562) and with various experimental data. We have found subtle structural changes in the lipid bilayer in the presence of the anesthetic compared with the pure lipid bilayer: a small lateral expansion is accompanied by a modest contraction in the bilayer thickness. However, the overall increase in the system volume is found to be comparable to the molecular volume of the added anesthetic molecules. No significant change in the hydrocarbon chain conformations is apparent. The observed structural changes are in fair agreement with NMR data corresponding to low anesthetic concentrations. We have found that halothane exhibits no specific binding to the lipid headgroup or to the acyl chains. No evidence is obtained for preferential orientation of halothane molecules with respect to the lipid/water interface. The overall dynamics of the lipid-bound halothane molecules appears to be reminiscent of that of other small solutes (Bassolino-Klimas et al., 1995. J. Am. Chem. Soc. 117:4118-4129).

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1988

Neurocysticercosis. Two hundred thirty-eight cases from a California hospital.

Neurocysticercosis is no longer a medical curiosity in the United States. Two hundred thirty-eight patients with neurocysticercosis were studied between 1981 and 1986 at the Los Angeles County-University of Southern California Medical Center, Los Angeles. Presenting signs and symptoms were protean--ranging from a single convulsion to coma and death. Fifty-one patients (21%) presented with an acute increase in intracranial pressure. There were 71 patients who ultimately required a shunting procedure or craniotomy. Presentation, diagnosis, management, and laboratory adjuncts (the role of cysticercosis titers and the electroencephalogram) are discussed. Mortality and morbidity can be reduced by maintaining a high degree of suspicion in populations at increased risk for cysticercosis.

Adolescent↗
PubMedDate not supplied

Lipomas of the mesencephalic tectum and rostral pons associated with sleep apnea syndrome.

Two patients with mixed sleep apnea and autopsy-documented lipomas of the mesencephalic tectum and rostral pons are presented. Microscopically, the locus ceruleus was unilaterally invaded by a tumor in one case and may have been compressed in the other. Adipocytes and fibrous tissue were present adjacent to pial surfaces and around small blood vessels within the parenchyma. There was prominent astrogliosis in the adjacent neuropil. Although respiratory control is a complex, multifocal phenomena, these findings raise the possibility that the locus ceruleus or adjacent brain stem regions may be affected in some instances of sleep apnea.

Adult↗