Search PubMed⌕ Search

Biomedical subjects

R M Levy

Publications and source records attributed to R M Levy.

At least 91 records · Page 5Linked to original sources
PubMed1986

Computer simulations of macromolecular dynamics: models for vibrational spectroscopy and X-ray refinement.

The use of computer simulations to study the internal dynamics of globular proteins and nucleic acids has attracted a great deal of attention in recent years. These simulations constitute the most detailed theoretical approach available for studying internal motions and structural flexibility of biological macromolecules. In this paper we review recent work concerned with the use of computer simulations for the interpretation of, and comparison with, experimental probes of molecular dynamics. New methods for calculating vibrational spectroscopic lineshapes from computer simulations are discussed. A quasiharmonic approximation is described by which classical computer simulations on multidimensional potential surfaces can be used to estimate the effects of anharmonicity on vibrational spectra. A novel aspect of the method is the use of normal-mode eigenvectors as the independent coordinates for Monte Carlo sampling. Results for isolated small molecules and liquid water are reviewed. The construction of vibrational lineshapes from quantum computer simulations using path integral methods with new (quasiharmonic and variable quadratic) reference systems are discussed. Results for small model systems are presented and extension of the methods to large molecules is discussed. The recent use of molecular dynamics simulations to analyze X-ray refinement models for proteins and nucleic acids is also reviewed.

Biopolymers↗
PubMed1986

Vancomycin penetration of a brain abscess: case report and review of the literature.

A 56-year-old man developed an abscess within a right parietal cystic anaplastic astrocytoma 3 days after removal of iodine-125 sources placed 9 days earlier for interstitial radiation therapy. After treatment with cephalosporin antibiotics proved unsuccessful, the patient was treated with intravenous vancomycin and intermittent percutaneous drainage of the abscess. Vancomycin levels obtained from the brain abscess fluid, both before and during later operative removal of the abscess, were 15 and 18 micrograms/ml, respectively; the serum vancomycin level was 21 micrograms/ml. This is the first report of the excellent penetration of vancomycin into brain abscess fluid.

Astrocytoma↗
PubMed1986

Neuroradiologic findings in AIDS: a review of 200 cases.

The radiologic studies of 200 consecutive AIDS patients with neurologic symptoms were evaluated to determine their diagnostic specificity and prognostic value. Of 81 patients with initially normal CT scans, four (5%) later developed progressive neurologic illness. Of 75 patients with CT evidence of diffuse cerebral atrophy, 12 (16%) later developed CT abnormalities or had postmortem CNS disease. CT scans showed mass lesions initially in 44 patients and later in an additional seven patients. Although toxoplasma gondii infection was the most frequent cause of these lesions, the CT characteristics of cerebral toxoplasmosis are too nonspecific to warrant diagnosis without biopsy. Preliminary evidence suggests that MRI may be more sensitive than CT in detecting intracranial disease in patients with AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Combined magnetic resonance imaging and bihemispheric magnetic resonance spectroscopy in acute experimental focal cerebral ischemia.

Combined magnetic resonance imaging (MRI) and 31P-magnetic resonance spectroscopy (MRS) were employed to evaluate acute regional cerebral ischemia in cats following middle cerebral artery occlusion (MCAO). MRI changes were first reliable 3 hours after MCAO; progressive increases in T1 and T2 relaxation times were noted for 12 hours after MCAO. Immediately after MCAO, 31P-MRS revealed decreased phosphocreatine (PCr) and increased inorganic phosphate (Pi); the PCr/Pi ratio fell from 2.23 +/- 0.40 to 0.68 +/- 0.04 (p less than 0.005). This relative decrease in high energy phosphates improved significantly by 3-5 hours after MCAO (0.67 +/- 0.04 versus 1.00 +/- 0.03, p less than 0.001). By 12 hours, the ratio had increased by 27 per cent. The dissociation between the progressive MRI changes and the gradual improvement in 31P-MRS suggests a difference between the processes affecting proton distribution and phosphate metabolism in acute regional ischemia.

Acute Disease↗
PubMed1985

Molecular dynamics of myoglobin at 298 degrees K. Results from a 300-ps computer simulation.

We have carried out a very long (300 ps) molecular dynamics simulation of the protein myoglobin. This trajectory is approximately three times longer than the longest previous molecular dynamics simulation of a protein, and ten times longer than protein simulations of comparable size (1,423 atoms in our model). Here we report results from this long simulation concerning the average structure, the mean square fluctuations of atoms about the average structure, and the nuclear magnetic resonance order parameters for various groups in myoglobin. The results demonstrate that the average coordinates change very slowly during the simulation. The relative atomic mobilities are well described by the simulation. For both the mean square atomic fluctuations and the order parameters, however, there are significant quantitative differences when values calculated using shorter portions of the trajectory are compared with results obtained for the entire 300-ps simulation. The implications of this result for obtaining converged properties from protein molecular dynamics simulations for comparison with experiment are discussed.

Leucine↗
PubMed1985

Neurological manifestations of the acquired immunodeficiency syndrome (AIDS): experience at UCSF and review of the literature.

In this review of the acquired immunodeficiency syndrome (AIDS), the authors have evaluated a total of 352 homosexual patients with AIDS or generalized lymphadenopathy managed at the University of California, San Francisco (UCSF), between 1979 and 1984. Of an initial unselected group of 318 patients, 124 (39%) were neurologically symptomatic, and one-third already had their neurological complaints at the time of presentation. An additional 210 AIDS patients with neurological symptoms have been reported in the literature. Thus, a total of 366 neurologically symptomatic patients with AIDS or lymphadenopathy are reviewed. Central nervous system (CNS) complications, encountered in 315 patients, included the following viral syndromes: subacute encephalitis (54), atypical aseptic meningitis (21), herpes simplex encephalitis (nine), progressive multifocal leukoencephalopathy (six), viral myelitis (three), and varicella-zoster encephalitis (one). Non-viral infections were caused by Toxoplasma gondii (103), Cryptococcus neoformans (41), Candida albicans (six), Mycobacteria (six), Treponema pallidum (two), coccidioidomycosis (one), Mycobacterium tuberculosis (one), Aspergillus fumigatus (one), and Escherichia coli (one). Neoplasms included primary CNS lymphoma (15), systemic lymphoma with CNS involvement (12), and metastatic Kaposi's sarcoma (three). Cerebrovascular complications were seen in four patients with hemorrhage and five with infarction. Five patients in the UCSF series had multiple intracranial pathologies, including two cases of simultaneous Toxoplasma gondii infections and primary CNS lymphoma, two cases of coexistent Toxoplasma gondii and viral infections, and one case of combined Toxoplasma gondii and atypical mycobacterial infection. Cranial or peripheral nerve complications, seen in 51 patients, included cranial nerve syndromes secondary to chronic inflammatory polyneuropathy (five), lymphoma (five), and Bell's palsy (five). Peripheral nerve syndromes included chronic inflammatory polyneuropathy (12), distal symmetrical neuropathy (13), herpes zoster radiculitis (six), persistent myalgias (two), myopathy (two), and polymyositis (one). In light of the protean behavior of AIDS and the problems related to the clinical, radiological, and serological diagnosis of the unusual and varied associated nervous system diseases, patients with AIDS and neurological complaints require a rigorous and detailed evaluation. The authors' experience suggests that biopsy of all CNS space-occupying lesions should be performed for tissue diagnosis prior to the institution of other therapies.

Acquired Immunodeficiency Syndrome↗
PubMed1984

Central nervous system mass lesions in the acquired immunodeficiency syndrome (AIDS).

The authors present the cases of nine patients with acquired immunodeficiency syndrome (AIDS) and intracerebral mass lesions, who were evaluated at the University of California, San Francisco, between April, 1979, and July, 1983. Eight patients were confirmed homosexual males, and none was Haitian . Their average age was 38.8 years. Tissue diagnosis was made in all patients from brain biopsy or autopsy material. Three patients initially presented for evaluation of their neurological deficits, while the other six already carried the diagnosis of AIDS at admission. Seven patients presented with multiple intracranial lesions and two had polymicrobial infection. In this series, three patients had Toxoplasma gondii brain abscesses, two had primary lymphoma, two had metastatic Kaposi's sarcoma of the central nervous system (CNS), two had focal cytomegalovirus encephalitis and one each had cryptococcal and Candida albicans brain abscesses. The clinical presentation, radiological evaluation, and serodiagnostic study of these patients were not helpful in establishing the nature of the CNS lesions. Brain biopsy is considered by the authors to be critical for the evaluation and appropriate treatment of mass lesions in patients with AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1983

Studies of nuclear magnetic resonance imaging and regional cerebral glucose metabolism in acute cerebral ischemia: possible mechanism of opiate antagonist therapeutic activity.

Using unilateral carotid artery ligation in the gerbil as a model of cerebral ischemia, both nuclear magnetic resonance (NMR) imaging and a newly developed double-label autoradiographic technique have been employed to investigate the physiologic mechanism of opiate action during cerebral ischemia. While several parameters of the NMR image have been demonstrated to reflect focal cerebral ischemic lesions, neither 2 mg/kg naloxone nor 10 mg/kg morphine sulfate had an effect on any of the parameters of the NMR image at any time point during the 24 hr experiment. While no consistent changes could be measured in the metabolic rate immediately about the ischemic region, results from double-label 2-deoxyglucose autoradiographic studies indicate that there are marked focal increases in metabolic rate in several subcortical nuclei bilaterally following the administration of naloxone. While no significant change was noted in the thalamus or arcuate nucleus, naloxone produced a significant elevation in glucose metabolic rate in the substantia nigra, periaqueductal grey and the red nucleus. The significance of these effects are discussed and a mechanism for the beneficial effect of opiate antagonists on neurologic deficit following ischemic cerebral lesions is proposed.

Animals↗
PubMed1983

Combined effect of restricted rotational diffusion plus jumps on nuclear magnetic resonance and fluorescence probes of aromatic ring motions in proteins.

A simple model is presented for the motion of phenylalanine and tyrosine rings in proteins. The model consists of restricted rotational diffusion of the rings about the side chain C alpha--C beta (chi 1) and C beta--C gamma (chi 2) axes combined with 180 degree ring flips. The model is used to evaluate order parameters for nuclear magnetic resonance relaxation and fluorescence depolarization probes of aromatic ring motions in proteins. The dependence of the order parameters on orientation in the ring plane is examined and it is demonstrated that in the presence of ring flips, additional ring librations can have a large effect on the probe order parameters.

Chemical Phenomena↗
PubMed1983

Normal mode paths for hydrogen exchange in the peptide ferrichrome.

Possible paths for exposure to solvent and hydrogen exchange of the amide protons of ferrichrome, a cyclic hexapeptide, are examined. The paths are obtained from calculations of the vibrational normal modes of ferrichrome and correspond to low energy atomic displacements away from the local minimum in the multidimensional conformational space of the molecule. Exposure of exchangeable groups along the normal modes was determined by using the solvent accessible surface area algorithm of Lee and Richards. Three of the exchangeable protons (Gly(1,2,3,)) are largely exposed to solvent in the x-ray structure while the remaining three exchangeable protons of the ornithines are totally shielded from solvent. A very small number of normal mode displacements are found to expose the Orn(2) and Orn(3) amide groups while the Orn(1) amide proton remains shielded from solvent for all the paths studied. The effective paths for exposure of Orn(2) and Orn(3) correspond to the lowest frequency ( approximately 18 cm(-1)) motions. The paths are characterized in terms of the magnitude and energy of atomic displacements, correlated changes in dihedral angles, and the resulting changes in exposure and hydrogen bonding of exchangeable groups.

Journal Article↗
PubMed1982

Dipolar NMR relaxation of nonprotonated aromatic carbons in proteins. Structural and dynamical effects.

The crystal structure and a 96-ps molecular dynamics simulation used to analyze structural and motional contributions to spin-lattice (T1) relaxation times of phenylalanine and tyrosine C gamma carbons of the pancreatic trypsin inhibitor. The H beta and H delta protons geminal to C gamma are calculated to account for approximately 80% of the dipolar relaxation for each residue. Experimental T1 values for the phenylalanine residues obtained at 25 MHz are observed to be 15-25% longer than estimates based on the rigid crystal structure. It is shown how an increase in T1 can be related to order parameters for the picosecond motional averaging of the important C,H dipolar interactions, and how these order parameters can be calculated from a protein molecular dynamics trajectory.

Animals↗
PubMed1982

alpha-Helix dipole model and electrostatic stabilization of 4-alpha-helical proteins.

A simple dipole model is developed for estimation of the electrostatic interaction energy between alpha-helices in proteins. This model is used to estimate the electrostatic stabilization in a recurrent protein tertiary structural motif, an array of four closely packed alpha-helices. It is found that, for the proteins examined (cytochrome c', hemerythrin, myohemerythrin, cytochrome b562, and a T4 phage lysozyme domain), their common antiparallel arrangement of adjacent helices confers a stabilization of 5--7 kcal/mol (1 cal = 4.18 J). In contrast, a similarly packed array of parallel helices is relatively destabilized by 20 kcal/mol. These results show that helix-dipole interactions are important in the stabilization of this structural motif. These effects are discussed both in the context of folding pathways for 4-alpha-helical proteins and the stabilization of the higher aggregates.

Chemical Phenomena↗
PubMed1982

Molecular dynamics of an alpha-helical polypeptide: Temperature dependence and deviation from harmonic behavior.

The mean square amplitudes of atomic fluctuations for a polypeptide (decaglycine) alpha-helix evaluated from molecular dynamics simulations at seven temperatures between 5 and 300 K are compared with analytic harmonic results and with experimental values. Above 100 K the harmonic approximation significantly underestimates the amplitudes of the displacements. Analysis of the time dependence of the fluctuations shows that low-frequency modes (<75 cm(-1)) dominate the atomic fluctuations and that there is a contribution with a very long relaxation time (>10 ps). Quantum corrections to the amplitude of the fluctuations are found to be small above 50 K. The mean square amplitudes obtained from the molecular dynamics simulations are compared with the values derived from x-ray temperature (Debye-Waller) factors for metmyoglobin (80, 250, and 300 K) and ferrocytochrome c (300 K).

Journal Article↗