Search PubMed⌕ Search

Biomedical subjects

R M Levy

Publications and source records attributed to R M Levy.

At least 55 records · Page 3Linked to original sources
PubMed1994

Molecular mechanics and electrostatic effects.

Continuum solvent models predict a quadratic charge dependence (linear response) of the free energy of a system of charged solutes. The relation between this prediction and the structure of the solvation shell around the solutes is discussed. Studies of the derivative of the free energy with respect to the charges for different reference states are shown to be a convenient way of testing the linear response assumption without resorting to the standard free energy perturbation method. We illustrate this with a system of two oppositely charged ions in aqueous solution, where nonlinearities are observed before the full charging process is completed. Since molecular mechanics (MM) simulations preserve the full nonlinearity of the problem, they are well suited to the investigation of the conditions under which linear response accurately reflects the behavior of the system. The error when using linear response theory to calculate the free energies of charging is estimated to be as large as 10-20%.

Chemical Phenomena↗
PubMed1994

Brain abscess and subdural empyema.

Notable contributions have been made recently in the diagnosis and management of brain abscesses and subdural empyema. Several articles present an international perspective, echoing much of the Western literature, including a profound decrease in mortality with the availability of computed tomography and early recognition and treatment. Diagnostic studies have highlighted the superiority of magnetic resonance imaging to computed tomography in the detection of subdural empyema and the potential value of positron emission tomography. Novel diagnostic tools, including 99mTc-hexamethylpropyleneamine oxime leukocyte scintigraphy and C-reactive protein levels, have been evaluated and show great promise. Surgical studies comparing stereotactic drainage with craniotomy for brain abscesses and burr hole versus craniotomy drainage of subdural empyema suggest the efficacy of these more limited procedures. Local instillation of antibiotics is a potentially effective adjunct for refractory brain abscesses. Recent studies suggest that the most significant predictors of poor outcome are the patient's level of consciousness and the rapidity of disease progression prior to the initiation of treatment.

Brain Abscess↗
PubMed1994

Consensus conference on the neurosurgical management of pain.

On the recommendation of the American Association of Neurological Surgeons Section on Pain, a satellite conference was organized for the 1993 annual meeting to work toward a consensus regarding the indications, expected outcomes, and potential complications of neurosurgical procedures for intractable pain. Twenty-two experts in the field attended this 2-day conference to consolidate our understanding of the role of neurosurgical procedures in pain management and to review critically the methodologies for clinical studies. With the support of the Section on Pain, this consensus development process will continue in order to refine the application and study of neurosurgical procedures for pain.

Algorithms↗
PubMed1993

The neurologic complications of human immunodeficiency virus infection.

The physician caring for HIV-1-infected patients must have a good working knowledge of the broad spectrum of neurologic diseases that occur in association with this infection. As with any other neurologic disorder, the site of the neuraxis that is affected must be properly identified. In HIV-1-infected persons, more than one site may be involved simultaneously, such as the coexistence of myelopathy and peripheral neuropathy, often resulting in a confusing array of neurologic signs and symptoms. The frequent occurrence of two or more diseases affecting the neuraxis, such as progressive multifocal leukoencephalopathy and toxoplasmosis, further complicates the picture. With the AIDS patient, the physician cannot rely on the clinical adage that all attempts should be made to ascribe the patient's problems to one disease. Often, it is not the case. As with other illnesses, the approach to the HIV-1-infected person with neurologic disease needs to be thorough and fluid. After rendering a diagnosis and embarking on therapy, the physician needs to be open minded about the possibility of an incorrect or additional diagnosis not previously considered. Lastly, despite all the knowledge that has been accumulated in the first decade of the AIDS epidemic, new illnesses occurring with HIV-1 infection are recognized with regularity. The physician must always bear in mind that the illness with which he or she is confronted may be one that has not been previously described.

AIDS-Related Opportunistic Infections↗
PubMed1993

Global folding of proteins using a limited number of distance constraints.

A Monte Carlo method is presented which can obtain the correct tertiary fold of a protein given the secondary structure and as few as three interactions between each secondary structure unit. This method was used to fold hemerythrin, flavodoxin, bovine pancreatic trypsin inhibitor and a variable light domain from an immunoglobulin using the known secondary structures of these proteins. Each of the proteins was successfully folded to obtain a structure resembling the initial X-ray structure. Reasonable success was also achieved when using a secondary structure prediction algorithm to assign secondary structure. The r.m.s. deviations between the folded proteins and the crystal structures are in the order of 3-5 A for the backbone coordinates. Evaluation of the r.m.s. deviations between members of the globin family indicates that two equivalent overall folds may have r.m.s. deviations of this or even larger magnitude. The limiting number of constraints necessary to achieve the correct fold is discussed.

Algorithms↗
PubMed1993

Neuromodulation techniques for medically refractory chronic pain.

Advances in our knowledge of the physiology of pain transmission and modulation have created new surgical options for the control of chronic pain. The pain modulation network can be activated by administration of spinal opiates or by electrical stimulation of the nervous system with transcutaneous, peripheral nerve, spinal cord, and deep brain stimulation. The theoretical basis and the clinical applications of neurostimulation for the treatment of medically intractable chronic pain are reviewed.

Chronic Disease↗
PubMed1993

Systemic T-cell lymphoma presenting with isolated neurological dysfunction and intraparenchymal brain lesions. Case report.

Secondary non-Hodgkin's lymphoma of the central nervous system is typically a late manifestation of systemic T-cell lymphoma, with a 2-month median survival time after the development of neurological disease. Of the reported patients with this late complication, only 1% manifest spread of the disease to the brain parenchyma. The authors report a patient with an unusual initial neurological presentation of systemic T-cell lymphoproliferative disorder and associated space-occupying lesions of the brain parenchyma. The diagnosis was supported by extensive molecular, immunological, and histopathological analysis. Neurological symptoms appeared early in the course of systemic disease and were characterized by spontaneous exacerbations and remissions. The patient has survived for more than 5 years since the onset of his neurological symptoms. Histopathological characterization including immunoperoxidase staining for T-cell markers, DNA content, and cell-cycle analysis of brain tissue obtained at stereotactic biopsy were compared to those of atypical lymphoid cells of peripheral blood, bone marrow, and liver. The neurological manifestations and possible etiologies of T-cell lymphoma are discussed.

Adult↗
PubMed1992

Molecular dynamics simulation of solvated protein at high pressure.

We have completed a molecular dynamics simulation of protein (bovine pancreatic trypsin inhibitor, BPTI) in solution at high pressure (10 kbar). The structural and energetic effects of the application of high pressure to solvated protein are analyzed by comparing the results of the high-pressure simulation with a corresponding simulation at low pressure. The volume of the simulation cell containing one protein molecule plus 2943 water molecules decreases by 24.7% at high pressure. This corresponds to a compressibility for the protein solution of beta = 1.8 x 10(-2) kbar-1. The compressibility of the protein is estimated to be about one-tenth that of bulk water, while the protein hydration layer water is found to have a greater compressibility as compared to the bulk, especially for water associated with hydrophobic groups. The radius of gyration of BPTI decreases by 2% and there is a one third decrease in the protein backbone atomic fluctuations at high pressure. We have analyzed pressure effects on the hydration energy of the protein. The total hydration energy is slightly (4%) more favorable at high pressure even though the surface accessibility of the protein has decreased by a corresponding amount. Large pressure-induced changes in the structure of the hydration shell are observed. Overall, the solvation shell waters appear more ordered at high pressure; the pressure-induced ordering is greatest for nonpolar surface groups. We do not observe evidence of pressure-induced unfolding of the protein over the 100-ps duration of the high-pressure simulation. This is consistent with the results of high-pressure optical experiments on BPTI.(ABSTRACT TRUNCATED AT 250 WORDS)

Aprotinin↗
PubMed1992

The efficacy of image-guided stereotactic brain biopsy in neurologically symptomatic acquired immunodeficiency syndrome patients.

A prospective series of 50 neurologically symptomatic human immunodeficiency infected patients with intracranial lesions who underwent image-guided stereotactic brain biopsy is presented. Patients were diagnosed with primary central nervous system lymphoma (14 patients), progressive multifocal leukoencephalopathy (14 patients), toxoplasmosis (13 patients), human immunodeficiency virus encephalitis (3 patients), infarction (2 patients), and 1 patient each with metastatic adenocarcinoma, metastatic melanoma, cryptococcoma, and atypical mycobacterial infection. Two of the patients with toxoplasmosis had a second intracranial abnormality. Two biopsies resulted in either descriptive diagnosis only or were nondiagnostic; the definitive diagnostic efficacy of image-guided stereotactic biopsy was thus 96%. No deaths were incurred as a result of biopsy. Four intraoperative or postoperative hemorrhages occurred; in only 1 patient was there a residual neurological deficit related to the surgery. Image-guided stereotactic biopsy may thus be considered both safe and effective in this patient population.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Progressive multifocal leukoencephalopathy in patients with HIV infection: lack of impact of early diagnosis by stereotactic brain biopsy.

Thirteen patients with HIV-related progressive multifocal leukoencephalopathy (PML), representing an institutional incidence of 4.2%, are reported. All cases were diagnosed by image guided stereotactic brain biopsy shortly after their presentation for neurologic complaints. All patients were males; risk factors included homosexual or bisexual activity or intravenous drug use. At the time of presentation with PML, the mean T4 count was 85 (range 9-240 cells/mm3). The most common neurologic symptoms were cognitive dysfunction and aphasia, whereas gait abnormalities and disordered cognition were the most common neurologic signs. Cerebrospinal fluid analysis was helpful only to rule out other causes of CNS disease. Magnetic resonance imaging, more sensitive than computed tomography (CT) scanning, typically revealed multiple areas of increased intensity on T2 weighted images although unifocal disease was seen in 23% of patients. Despite early stereotactic biopsy and aggressive symptomatic therapy, survival of these patients was poor with a mean of 2.6 months after the onset of neurological symptoms and 2.0 months after biopsy.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Neurosurgical aspects of human immunodeficiency virus infection.

The spectrum of neurologic disease that complicates human immunodeficiency virus (HIV) is extremely broad. This article deals with those HIV-related diseases that may occur with a frequency of more than 1% and are of potential neurosurgical importance: those that result from a direct involvement of the nervous system by HIV and those that result either directly or indirectly from the concomitant immunosuppression. Infectious complications are the most common but not the sole cause of neurologic disability in the latter category. Other causes of neurologic disease seen in association with HIV infection include neoplasms, metabolic-nutritional disorders, and vascular complications.

AIDS Dementia Complex↗
PubMed1991

MRI-guided stereotaxic brain biopsy in neurologically symptomatic AIDS patients.

Two patients with AIDS-related neurologic dysfunction were evaluated with both computed tomographic (CT) brain scans and magnetic resonance imaging (MRI). CT scans were essentially normal in both patients while MRI revealed focal lesions amenable to brain biopsy. Using newly developed instrumentation, MRI-guided stereotaxic brain biopsy was performed without complication. The benefits and impact of this new technology for the care of neurologically symptomatic AIDS patients is discussed.

AIDS Dementia Complex↗
PubMed1990

Determining local conformational variations in DNA. Nuclear magnetic resonance structures of the DNA duplexes d(CGCCTAATCG) and d(CGTCACGCGC) generated using back-calculation of the nuclear Overhauser effect spectra, a distance geometry algorithm and constrained molecular dynamics.

Two-dimensional nuclear magnetic resonance (n.m.r.) spectroscopy and a variety of computational techniques have been used to generate three-dimensional structures of the two DNA duplexes d(CGCCTAATCG) and d(CGTCACGCGC). The central six base-pairs in these two decamers contain all ten dinucleotide pairs in DNA and thus, represent a model system for investigating how the local structure of DNA varies with base sequence. Resonance assignments were made for the non-exchangeable base protons and most of the C-1'-C-4' sugar protons in both decamers. Three-dimensional structures were generated using a distance geometry algorithm and these initial structures were refined by optimizing the fit of back-calculated spectra against the experimental two-dimensional nuclear Overhauser effect (NOE) spectra. This back-calculation procedure consists of calculating NOE cross relaxation rates for a given structure by solution of the Bloch equations, and directly accounts for spin diffusion effects. Use of this refinement procedure eliminates some assumptions that have been invoked when generating structures of DNA oligomers from n.m.r. data. Constrained energy minimization and constrained quenched molecular dynamics calculation were also performed on both decamers to help generate energetically favorable structures consistent with the experimental data. Analysis of the local conformational parameters of helical twist, helical rise, propeller twist, displacement and the alpha, beta, gamma, epison and zeta backbone torsion angles in these structures shows that these parameters span a large range of values relative to the X-ray data of nucleic acids. However, the glycosidic and pseudorotation angles are quite well defined in these structures. The implications that these results have for determination of local structural variations of DNA in solution, such as those predicted by Callidine's rules, are discussed. Our results differ significantly from some previous studies on determining local conformations of nucleic acids and comparisons with these studies are made.

Algorithms↗
PubMed1990

Analysis of side-chain conformational distributions in neutrophil peptide-5 NMR structures.

The side-chain conformations have been analyzed in the antimicrobial peptide, Neutrophil Peptide-5 (NP-5), whose structure was independently generated from nmr-derived distance constraints using a distance geometry algorithm. The side-chain and peptide dihedral angle distributions in the nmr structures were compared with those constructed from a data base of high-resolution protein crystal structures. The side-chain conformational preferences for NP-5 in solution are significantly different from those observed in the crystal structure data base. These results indicate that the side-chain conformations are quite disordered for many of the residues of NP-5. The absence of a correlation between the width of the conformational distribution and surface accessibility suggests that the disorder may be due to limitations in the structural information extracted from the nmr data rather than to molecular motion. However, it is also observed that the degree of conformational disorder is only weakly correlated with the number of nuclear Overhauser enhancements to a given side chain. Possible reasons for this are discussed. Molecular mechanics refinement of these structures did not significantly change the side-chain populations. Anomolously wide distributions are observed for rotations about the peptide bonds and the disulfide bonds in the NP-5 distance geometry structures, which are improved by the refinement. The very high degree of order observed for the central dihedral angle of the disulfide bond in the high-resolution crystal data base suggests that the rotation about this bond in proteins is determined by the local potential.

Algorithms↗
PubMed1990

Primary central nervous system lymphomas: natural history and response to radiation therapy in 55 patients with acquired immunodeficiency syndrome.

The incidence of primary central nervous system (CNS) lymphoma has increased rapidly in patients with acquired immunodeficiency syndrome (AIDS) and is predicted to exceed 1800 cases annually by 1991. To characterize the natural history and response to radiation therapy (RT) of these lesions, the authors have reviewed the clinical histories of 55 AIDS patients with biopsy-proven primary CNS lymphomas. The tumors responded both clinically and radiologically to whole-brain RT consisting of 4000 rad in 267-rad fractions over 3 weeks or an equivalent neuroret dose. The mean duration of survival from the appearance of symptoms consistent with the mass lesion was significantly greater in patients who received RT than in those who did not (42 vs. 134 days, p less than 0.5; median 27 vs. 119 days). Autopsy findings showed that patients who did not receive RT died from tumor progression, whereas those who completed RT died of opportunistic infections. Patients with AIDS who are suspected of having primary CNS lymphoma should therefore immediately undergo biopsy and, if the diagnosis is confirmed, whole-brain RT. With early diagnosis and treatment, these tumors respond to, and patients benefit from, RT. Survival of such patients may in future be prolonged by more effective treatments for systemic opportunistic infections.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Neurologic complications of HIV infection.

The nervous system is profoundly affected by acquired immunodeficiency syndrome. Nervous system pathology is responsible for the initial symptoms in 10 percent of AIDS patients and is found at autopsy in 75 percent of patients with AIDS. Human immunodeficiency virus can directly infect the brain, producing a dementia. It can also cause aseptic meningitis, spinal vacuolar myelopathy, distal symmetric peripheral neuropathy or inflammatory demyelinating polyradiculoneuropathy. The last condition may be effectively treated with plasmapheresis. Neurologic disorders due to other infectious agents are also common in AIDS patients.

AIDS Dementia Complex↗