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J M Levin

Publications and source records attributed to J M Levin.

At least 37 records · Page 2Linked to original sources
PubMed1997

Age-related reduction in functional MRI response to photic stimulation.

Many functional imaging studies have demonstrated age-related alterations in cerebral blood flow during the resting state. However, few studies have addressed possible differences in functional response to cerebral activation. We assessed the response of visual cortex to photic stimulation in 9 normal elderly subjects and 17 normal younger subjects with blood oxygenation level dependent functional magnetic resonance imaging. We found that the amplitude of response in elderly subjects was significantly decreased compared to younger subjects (2.5 +/- 1.0% versus 4.0 +/- 1.6%, p = 0.01), suggesting a reduction in functional activation or an age-related alteration in the coupling of blood oxygenation to focal activation.

Adult↗
PubMed1996

Abnormal cerebral metabolism in polydrug abusers during early withdrawal: a 31P MR spectroscopy study.

Phosphorus magnetic resonance spectroscopy (31P MRS) at 1.5 T was performed on nine polysubstance abusing men. All nine patients met DSM-III-R criteria for concurrent cocaine and heroin dependence, were neurologically normal, were negative for the human immunodeficiency virus, and had normal clinical brain MRI scans. Patients were scanned 2-7 days after admission to a drug treatment unit. Eleven age-matched control subjects also were studied. The ISIS localized phosphorus spectra were obtained from a 5-cm thick axial brain slice and a 100-cc white matter volume. In the brain slice, the phosphorus metabolite signal expressed as a percentage of total phosphorus signal was 15% higher for phosphomonoesters, 10% lower for nucleotide triphosphates (beta-NTP), and 7% lower for total nucleotide phosphates in polydrug abusers compared with those in controls. Phosphodiesters, inorganic phosphate, phosphocreatine, total phosphorus, pH, and free magnesium concentration were unchanged. None of these parameters correlated with the methadone dose or the number of days abstinence. Single photon emission computed tomographic imaging of a subgroup of the patients revealed abnormal cerebral perfusion in 80% of the patients scanned. These data suggest that cerebral high energy phosphate and phospholipid metabolite changes result from long term drug abuse and/or withdrawal and that these changes can be detected and studied by 31P MRS.

Adult↗
PubMed1996

Applications of dynamic susceptibility contrast magnetic resonance imaging in Neuropsychiatry.

Functional neuroimaging has assumed an important role in the cognitive and clinical neurosciences. Recently, substantial progress has been made toward developing functional magnetic resonance imaging techniques for the examination of cerebral hemodynamic changes that accompany brain function and toward earlier and better diagnosis of brain disease. Dynamic susceptibility contrast (DSC) MRI offers unique information about cerebral hemodynamics both at rest and in response to brain activation. We review the clinical applications of DSC MRI and present our experience with this modality in the evaluation of patients with neuropsychiatric disorders. Our experience suggests that DSC MRI may afford new insights into the diagnosis and treatment of cognitive disorders.

Blood Volume↗
PubMed1995

Sequential dynamic susceptibility contrast MR experiments in human brain: residual contrast agent effect, steady state, and hemodynamic perturbation.

The stability and reproducibility of the dynamic susceptibility contrast (DSC) MRI method for sequential relative cerebral blood volume (relCBV) measurements was evaluated to validate the method for use in quantitative studies of cerebral hemodynamics in humans. A spin echo echo planar imaging protocol was used in conjunction with multiple bolus injections of the susceptibility contrast agent gadoteridol (GD). The effects of variation in interbolus interval (10 min to 4 h), the number of injections (two to four), and the effect of the cerebral vasodilating agent acetazolamide (ACZ) were evaluated in 44 experiments performed with 22 normal subjects. Two fundamental observations were made. First, with multiple injections of GD, the change in MR signal over time was not consistent from first to subsequent boluses. A second bolus administered 10 min to 2 h after an initial bolus resulted in signal change of greater amplitude and duration, resulting in artifactually elevated estimates of relCBV, consistent with a residual effect of GD. Second, a relative steady state could be reached with serial injections of GD, such that the profile of subsequent boluses closely paralleled those of previous ones. This facilitates the reliable measurement of relCBV during activation, as demonstrated by use of ACZ.

Acetazolamide↗
PubMed1995

Clinical applications of functional MRI in neuropsychiatry.

Clinical neuroimaging is due for yet another sea change as functional neuroimaging becomes increasingly powerful and available. Functional magnetic resonance imaging (fMRI) is perhaps the most promising of the emerging techniques. The following review helps us understand the physics, strengths, limitations, and promise of fMRI. The authors are all affiliated with the Brain Imaging Center at McLean Hospital and with the Departments of Neurology (Dr. Levin) and Psychiatry (Dr. Renshaw) at Harvard Medical School.

Brain↗
PubMed1995

Improved regional cerebral blood flow in chronic cocaine polydrug users treated with buprenorphine.

UNLABELLED: Chronic cocaine and polydrug abuse have been associated with regional abnormalities in cerebral perfusion. The authors have previously demonstrated that these abnormalities are partially reversible after drug addiction treatment with buprenorphine. This study was designed to separate the effect on cerebral perfusion of abstinence from drug use from that of buprenorphine directly. METHODS: Fifteen cocaine- and heroin-dependent men were studied with 99mTc-hexamethylpropyleneamine oxime (HMPAO) brain SPECT. The men, all part of an inpatient drug abuse treatment research program, were randomly assigned after detoxification to receive placebo or either 6 or 12 mg daily buprenorphine treatment. SPECT studies were performed at baseline, after maximum dosage was reached and after tapering off the study drug. Studies were compared visually with regard to the number and location of perfusion defects by reviewers blinded to treatment assignment. RESULTS: Subjects receiving buprenorphine had a significant reduction in the number of defects per study between baseline and maximum buprenorphine dose as compared with those receiving placebo (decrease of 4 +/- 5.4 versus increase of 4.8 +/- 4.7, p = 0.006). These differences were dose-related. Improvement with buprenorphine was temporary, with return to baseline after tapering off. CONCLUSION: Buprenorphine treatment, and not abstinence from drug use alone, leads to improvement in regional cerebral perfusion abnormalities in chronic cocaine- and heroin-dependent men.

Adult↗
PubMed1994

Long term results of stereotactic brachytherapy used in the initial treatment of patients with glioblastomas.

BACKGROUND: Despite optimal therapy with surgery and radiotherapy, the prognosis of patients with glioblastomas remains poor. Stereotactic brachytherapy involves the accurate placement of radioactive isotopes within brain tumors, significantly increasing the dose of radiation that can be delivered to the tumor bed without substantial risk to surrounding normal tissue, potentially improving local tumor control and patient survival. METHODS: Between February 1987 and July 1993, the authors treated 56 patients with glioblastomas with stereotactic brachytherapy as part of their initial therapy. Patients underwent surgery, limited field external beam radiotherapy, and brachytherapy with temporary high-activity iodine 125 sources, giving an additional 50 Gy to the tumor bed. RESULTS: Median survival for patients undergoing brachytherapy was 18 months compared with 11 months for a matched brachytherapy control group with similar clinical and radiologic features (P < 0.0007). Survival rates at 1, 2, and 3 years after diagnosis of 83%, 34%, and 27%, respectively, for patients receiving brachytherapy were significantly increased compared with survival rates of 40%, 12.5%, and 9%, respectively, for control subjects. Thirty-six patients (64%) underwent reoperation for symptomatic radiation necrosis from 3 to 42 months (median, 11 months) after brachytherapy. The median survival of patients undergoing reoperation was 22 months compared with 13 months for those who did not have further surgery (P < 0.02). Thirty-five percent of patients relapsed locally within the brachytherapy target volume, whereas 65% had marginal or distant relapses. CONCLUSIONS: Brachytherapy may improve local tumor control and prolong survival when used in the initial treatment of selected patients with glioblastomas.

Adolescent↗
PubMed1994

HIV-specific T-helper activity in seronegative health care workers exposed to contaminated blood.

OBJECTIVE: To evaluate human immunodeficiency virus (HIV) type 1-specific cellular immune responses in HIV-seronegative health care workers with occupational high-risk exposures to HIV-infected (HIV-positive) patients. DESIGN: Peripheral blood mononuclear cells (PBMCs) were obtained after occupational exposures to HIV, and PBMCs from health care workers exposed to HIV-negative patients served as controls. The PBMCs were stimulated in vitro with HIV envelope synthetic peptides. Interleukin 2 (IL-2) production was measured in a bioassay. The HIV antibody status was determined by standard enzyme-linked immunosorbent assays. Exposed individuals were also evaluated for HIV proviral DNA by polymerase chain reaction techniques. PARTICIPANTS: The PBMCs from eight health care workers with high-risk exposures and nine control health care workers were studied. RESULTS: The PBMCs from all individuals showed strong IL-2 production to control antigens, indicating intact T-helper function. Interleukin 2 production to HIV peptides was detected in PBMCs from six of eight HIV-exposed individuals, but in only one of the nine health care workers exposed to HIV-negative body fluids (P < .008). None of the HIV-exposed health care workers became infected as determined by negative HIV antibody and polymerase chain reaction analysis after follow-up evaluation that ranged from 8 to 64 weeks. CONCLUSION: Human immunodeficiency virus-specific T-helper activity was detected in six (75%) of eight HIV-negative health care workers with exposure to HIV-positive body fluids. Potent HIV-specific T-helper activity was detectable 4 to 8 weeks after the exposure and was lost in individuals followed up for 8 to 64 weeks. Three health care workers remained responsive at 8, 19, and 24 weeks. Exposure to HIV without evidence of subsequent infection appears to result in activation of cellular immunity without activation of antibody production.

Adult↗
PubMed1994

Gender differences in cerebral perfusion in cocaine abuse: technetium-99m-HMPAO SPECT study of drug-abusing women.

UNLABELLED: Cocaine abuse continues to be a major public health concern, with a variety of medical and neurologic sequelae. Previous studies have demonstrated abnormalities in cerebral perfusion in chronic cocaine abusers and after acute administration of cocaine. Although women are becoming increasingly represented among drug abusers, few studies have included women. To the authors' knowledge, none has compared cerebral perfusion in asymptomatic women with that in men. METHODS: The cerebral perfusion of 13 cocaine-dependent women, 4 of whom were also heroin dependent, was studied with 99mTc hexamethylpropyleneamine oxime (HMPAO) SPECT. These women were compared with 13 cocaine-dependent men and 26 healthy control subjects. Structural brain lesions and neurologic abnormalities were excluded by MRI and neurologic evaluation. Perfusion studies were interpreted in a standardized fashion by reviewers blinded to clinical information. RESULTS: It was found that cocaine-dependent women were much less likely to have abnormal study findings than cocaine-dependent men (p = 0.003) and were indistinguishable from normal women (p = 1.0). However, the results in both women and men who concurrently used heroin plus cocaine were all abnormal. Perfusion abnormalities tended to be located in anterior brain structures, such as the frontal and temporal cortex and the basal ganglia. CONCLUSION: These data suggest that cocaine-dependent women have fewer abnormalities in cerebral perfusion than cocaine-dependent men, but that concurrent abuse of heroin and cocaine is associated with more perfusion abnormalities in both sexes.

Adult↗
PubMed1994

Hyperperfusion of ictal seizure focus demonstrated by MR perfusion imaging.

MR using a susceptibility-weighted sequence and dynamic contrast enhancement with gadolinium demonstrated relative hyperperfusion of the right temporoparietal cortex in a patient in focal status epilepticus. A single-photon emission CT (SPECT) scan also demonstrated hyperperfusion of the right temporoparietal cortex. Perfusion MR, SPECT, and electroencephalogram normalized when the seizures ended.

Adult↗
PubMed1993

Quantification of secondary structure prediction improvement using multiple alignments.

The use of multiple sequence alignments for secondary structure predictions is analysed. Seven different protein families, containing only sequences of known structure, were considered to provide a range of alignment and prediction conditions. Using alignments obtained by spatial superposition of main chain atoms in known tertiary protein structures allowed a mean of 8% in secondary structure prediction accuracy, when compared to those obtained from the individual sequences. Substitution of these alignments by those determined directly from an automated sequence alignment algorithm showed variations in the prediction accuracy which correlated with the quality of the multiple alignments and distance of the primary sequence. Secondary structure predictions can be reliably improved using alignments from an automatic alignment procedure with a mean increase of 6.8%, giving an overall prediction accuracy of 68.5%, if there is a minimum of 25% sequence identity between all sequences in a family.

Amino Acid Sequence↗
PubMed1993

In vitro susceptibility of Borrelia burgdorferi to 11 antimicrobial agents.

The in vitro susceptibility of Borrelia burgdorferi to 11 antimicrobial agents was investigated. The antimicrobial agents evaluated included ceftizoxime, FK037, cefotaxime, dirithromycin, clarithromycin and its metabolite 14-hydroxy-clarithromycin, erythromycin, doxycycline, amoxicillin, ciprofloxacin, and ofloxacin. Isolates of B. burgdorferi tested included two reference strains (B31 and ATCC 53899), six isolates from the midwestern United States, and three from Europe. A broth macrodilution method was used to determine MICs and MBCs. B. burgdorferi was inhibited by < or = 0.5 micrograms of each of the agents except the quinolones per ml. The MBCs for 90% of strains tested of ceftizoxime, FK037, clarithromycin, 14-OH clarithromycin, and dirithromycin (< or = 1.0 microgram of each per ml) were superior to those of amoxicillin (2.0 micrograms/ml) and doxycycline (4.0 micrograms/ml). Further in vivo studies are warranted to determine whether these agents may be efficacious in the treatment of Lyme borreliosis.

Anti-Bacterial Agents↗
PubMed1993

Complications of therapy for venous thromboembolic disease in patients with brain tumors.

Venous thromboembolic disease is a frequent complication in patients with intracranial malignancies. Because these patients are often perceived to be at increased risk of intracranial hemorrhage with anticoagulation, inferior vena cava (IVC) filters are frequently used in their treatment. We reviewed the records of 49 patients with intracranial malignancies and venous thromboembolic disease to determine the effectiveness of, and the complications resulting from, treatment. Of the 42 patients receiving IVC filters, a strikingly high percentage (62%) developed complications. Twelve percent developed recurrent pulmonary embolism, while 57% developed either IVC or filter thrombosis, recurrent deep venous thrombosis, or post-phlebitic syndrome. These complications severely reduced the quality of life of the affected patients. Only 15 of our patients were treated with anticoagulation, and seven of these received it because of continued thromboembolic disease. None of these 15 patients had proven hemorrhagic complications. This study suggests that the complication rate of IVC filters in patients with brain tumors is higher than commonly perceived and may outweigh the risk of anticoagulation.

Anticoagulants↗
PubMed1991

Mutational and structural analysis of the nitrate reductase heme domain of Nicotiana plumbaginifolia.

We have analyzed four Nicotiana plumbaginifolia null mutants presumably affected in the heme domain of nitrate reductase. The DNA sequence of this domain has been determined for each mutant and for the wild type. Two mutations were identified as single base changes leading to, respectively, the substitution of a histidine residue by an asparagine (mutant E56) and to the appearance of an ochre stop codon (mutant E64). Based on the amino acid sequence homology between the nitrate reductase heme domain and mammalian cytochrome b5, we have predicted the three-dimensional structure of this domain. This showed that the nitrate reductase heme domain is structurally very similar to cytochrome b5 and it also confirmed that the residue involved in E56 mutation is one of the two heme-binding histidines. The two other mutations (mutants A1 and K21) were found to be, respectively, -1 and +1 frameshift mutations resulting in the appearance of an opal stop codon. These sequence data confirmed previous genetic and biochemical hypotheses on nitrate reductase-deficient mutants. Northern blot analysis of these mutants indicated that mutant E56 overexpressed the nitrate reductase mRNA, whereas the nonsense mutations present in the other mutants led to reduced levels of nitrate reductase mRNA.

Amino Acid Sequence↗
PubMed1991

Towards understanding the glycoprotein hormone receptors.

Lutropin (LH), follitropin (FSH) and thyrotropin (TSH), as well as choriogonadotropin (CG, which binds to the LH receptor) constitute the glycoprotein hormone family. Their 3 receptors have been cloned during the last few months. They belong to the large group of G-protein coupled membrane proteins, with their specific N-terminal domain likely to bind the hormone and the characteristic 7 membrane-spanning segments in their C-terminal moiety. The present review discusses the main results of amino acid sequence analysis performed on the glycoprotein hormone receptors. The putative extracellular head exhibits less than 45% homology over the 3 receptors, while approximately 70% residue conservation is found in the transmembrane moiety. Here only, limited sequence homologies (approximately 20%) can be found with other G-protein coupled receptors. The secondary structure predictions performed on the 3 receptors revealed that the polypeptide sequence predicted as ordered (either alpha-helix or beta-strand) were repeated evenly throughout the extracellular head with a period of approximately 25 amino acids. This analysis helped to define the intervening loops between this ordered stretches as potential candidates for bearing at least part of the binding site of the hormones. Some of the perspectives opened by the cloning of the receptors are described, like the production of the extracellular head of the porcine LH receptor in baculovirus-infected insect cells, and the exploration of the LH receptor's mechanism of functioning as a dimer.

Amino Acid Sequence↗
PubMed1991

The protein structure code: what is its present status?

Current methods of prediction of protein conformation are reviewed and the algorithms on which they rely are presented. For non-homologous proteins and after cross-validation the reported methods exhibit a probability index, i.e. the per cent of correctly predicted residues per predicted residues, of 63-65% with a standard deviation of the order of 7% for three conformational states--helix, beta-strand and coil. This present limitation in the accuracy of predictions that use only the information of the local sequence can be related essentially to the effect of long-range interactions specific for each protein family. The methods based on sequence similarity can improve the accuracy of prediction by expressing explicitly the homology of the protein to be predicted with proteins in the database. In these circumstances the probability index can reach 87% with a standard deviation of 6.6%. This property can be used for modeling homologous proteins by aiding in amino acid sequence alignments. The prediction of the tertiary structure of a protein is still limited to the case of modeling a structure based on the known three-dimensional structure of a homologous protein.

Algorithms↗
PubMed1990

Erythromycin failure with subsequent Pasteurella multocida meningitis and septic arthritis in a cat-bite victim.

We report the case of a 75-year-old woman who developed Pasteurella multocida meningitis and septic arthritis while being treated for a cat-bite wound infection with erythromycin. Review of the literature revealed that erythromycin has poor in vitro activity against this bacterium and has been associated with serious clinical failures. We recommend that erythromycin not be prescribed for empiric therapy of established animal-bite infections. Suggestions for optimal empiric therapy of animal-bite infections and the differential diagnosis of severe cat-bite-associated sepsis are discussed.

Aged↗