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Biomedical subjects

J Peterson

Publications and source records attributed to J Peterson.

At least 109 records · Page 6Linked to original sources

Empirical techniques for determining the reliability, magnitude, and pattern of neuropsychological change after epilepsy surgery.

PURPOSE: We assessed test-retest neuropsychological performance in patients with complex partial seizures to derive reliable change indices (RCIs) and regression-based norms for change, indices that may be helpful in assessing cognitive outcome after anterior temporal lobectomy. METHODS: Forty patients with complex partial seizures (CPS) who did not undergo epilepsy surgery were administered a comprehensive neuropsychological battery on two occasions. Their test-retest data were used to compute both RCIs and regression-based norms for change for each neuropsychological index. RCIs corrected for practice effects provide a confidence interval (CI) indicating the degree of performance change required to exceed the variability attributable to sources of error (e.g., practice, test-retest reliability). Regression-based norms for change also correct for several sources of measurement error and examine observed versus expected test-retest changes on a common metric, thereby facilitating determination of the degree and relative magnitude of change across cognitive domains. RESULTS: Mean changes in test-retest performance were generally modest, but were evident across several test measures. Our data indicate a considerable degree of individual variability in test-retest performance. CONCLUSIONS: RCIs and regression-based norms are complementary indexes and can be particularly useful in examining the test-retest performance of individual patients who undergo epilepsy surgery as well as in the more general investigation of cognitive outcome after epilepsy surgery.

Adult↗

Interactions between the ankyrin repeat-containing protein Akr1p and the pheromone response pathway in Saccharomyces cerevisiae.

Akr1p, which contains six ankyrin repeats, was identified during a screen for mutations that displayed synthetic lethality with a mutant allele of the bud emergence gene BEM1. Cells from which AKR1 had been deleted were alive but misshapen at 30 degrees C and inviable at 37 degrees C. During a screen for mutants that required one or more copies of wild-type AKR1 for survival at 30 degrees C, we isolated mutations in GPA1, which encodes the G alpha subunit of the pheromone receptor-coupled G protein. (The active subunit of this G protein is G beta gamma, and G alpha plays an inhibitory role in G beta gamma-mediated signal transduction.) AKR1 could serve as a multicopy suppressor of the lethality caused by either loss of GPA1 or overexpression of STE4, which encodes the G beta subunit of this G protein, suggesting that pheromone signaling is inhibited by overexpression of Akr1p. Mutations in AKR1 displayed synthetic lethality with a weak allele of GPA1 and led to increased expression of the pheromone-inducible gene FUS1, suggesting that Akr1p normally (and not just when overexpressed) inhibits signaling. In contrast, deletion of BEM1 resulted in decreased expression of FUS1, suggesting that Bem1p normally facilitates pheromone signaling. During a screen for proteins that displayed two-hybrid interactions with Akr1p, we identified Ste4p, raising the possibility that an interaction between Akr1p and Ste4p contributes to proper regulation of the pheromone response pathway.

Amino Acid Sequence↗

Lifespan and lesions in genetically heterogeneous (four-way cross) mice: a new model for aging research.

Genetically heterogeneous animal models provide many advantages for research on aging but have been used infrequently. We present here lifespan and lesion data from a study of mice bred as a cross between (AKR/J x DBA/2J)F1 females and (C57BL/6J x SJL/J)F1 males. In such a four-way cross population, each mouse is genetically unique, but replicate populations of essentially similar genetic structure can be generated quickly, at low cost, and of arbitrary size from commercially available, genetically stable hybrid parents. We employed a protocol in which mice judged to be severely ill were euthanatized to obtain tissue in optimal condition for necropsy, and we were able to infer a likely cause of illness in 42 of 44 animals. Malignant lymphoma, including at least four histopathologically distinct subtypes, was the most common cause and was also a frequent incidental finding in mice dying of other causes. Neoplastic disease, benign or malignant, was the sole or a contributing cause of illness in 90% of the mice for which a cause could plausibly be assigned. A wide range of lethal and nonlethal degenerative lesions was also noted. The coefficient of variation for lifespan in these genetically heterogeneous mice was 26%, similar to that seen in analyses of recombinant inbred mouse lines. Baseline lifespan and pathology data on four-way cross mice is a useful prelude to the exploitation of this rodent model in tests of genetic and mechanistic hypotheses about aging.

Adenocarcinoma↗

Safety of commercial air travel following myocardial infarction.

BACKGROUND: Travelers occasionally suffer myocardial infarction (MI) while abroad. Existing guidelines recommend a 4- to 24-week convalescent period following MI before air travel should be permitted. HYPOTHESIS: Air travel may be undertaken safely in the early post-MI period. METHODS: The aeromedical transport records of two international medical assistance companies over a 3-yr period were reviewed. We identified 209 patients who suffered MI; 13 transported by private air ambulance were excluded. We reviewed the aeromedical transports of the remaining 196 adults carried on commercial aircraft between 3-53 d post-MI to investigate the safety of air travel in this group. Data were recorded regarding patient age; sex; location of MI; complications of MI; presence of medical escort; duration of flight(s); use of oxygen, medications, or cardiac monitoring during transport; and development of symptoms in flight. RESULTS: Within 7 d of their acute MI 3 patients (2%) were transported; 87 (44%) between days 8-14 post-MI; 65 (33%) between days 15-21; 27 (14%) between days 22-28; and 14 (7%) more than 28 d post-MI. Some 187 patients (95%) were transported without incident; 9 (5%) patients experienced symptoms requiring evaluation by the escorting physician. Of the 9, 6 problems occurred in patients being transported less than 14 d post-MI. Symptoms resolved spontaneously or immediately after physician intervention in all but one case. CONCLUSION: International aeromedical transport of patients may be safely accomplished 2-3 wk after an acute MI when an accompanying physician is present. Recommendations for delaying travel more than 4 wk after infarction are not supported by clinical experience and should be revised.

Adult↗

Determination of ventricular vulnerable period and ventricular fibrillation threshold by use of T-wave shocks in patients undergoing implantation of cardioverter/defibrillators.

BACKGROUND: This study was designed to characterize the ventricular vulnerable period (VVP) and ventricular fibrillation (VF) threshold by use of T-wave shocks in patients undergoing implantation of cardioverter/defibrillators. A premature condensed shock applied during the VVP can induce VF. Most studies on the VVP and VF threshold have been conducted in animals rather than in humans. METHODS AND RESULTS: Twenty-one patients undergoing implantation of Medtronic PCD Jewel 7219D cardioverter/defibrillators because of ventricular tachycardia and/or VF were enrolled. All had structural heart disease. Their ages ranged from 42 to 85 years (mean, 69 +/- 11.3 years). Seventeen (80.9%) had atherosclerotic coronary artery disease. The right ventricle (RV) was driven at a cycle length (S1) of 400 ms, and monophasic shocks (S2) of 0.6 J were delivered through an RV apex lead (cathode) and a superior vena cava lead (anode) during the T wave of each cardiac cycle. The longest and shortest S1-S2 intervals that were capable of inducing sustained VF were defined as the outer and inner limits of the VVP at an energy level of 0.6 J, respectively. To determine the VF threshold, a shock of 0.2 J was applied at the midpoint of the VVP at 0.2-J increments until sustained VF was induced. The lowest energy setting capable of inducing sustained VF was defined as the VF threshold. Of the 21 patients, the VVP at an energy level of 0.6 J averaged 53.8 +/- 26.0 ms. Characteristically, the VVP started from the ascending limb of the T wave and ended at or slightly beyond the peak of the T wave, occupying 12.2 +/- 5.8% of the QT interval. The midpoint of the VVP used for determination of the VF threshold measured 0 to 90 ms (mean, 32.9 +/- 26.0 ms) before the peak of the T wave. Of the 21 patients, 16 (76.2%) had a VF threshold at < or = 0.2 J (estimated 57 V), 3 at 0.4 J (estimated 81 V), and 2 at 0.6 J (estimated 99 V). CONCLUSIONS: The VF threshold is low (< or = 0.2 J) in the majority of patients requiring implantation of cardioverter/defibrillators. Further studies are needed to define clinical usefulness of the study technique relative to its potential role for risk stratification and for assessing antifibrillatory properties of antiarrhythmic drugs in this subset group of patients.

Adult↗

The site of the redox-linked proton pump in eukaryotic cytochrome c oxidases.

The electronic spectra of fully oxidized derivatives of some cytochrome c oxidase preparations are distinctly pH dependent. In general, the observed spectral shifts are greater in the case of pulsed derivatives compared to resting preparations and also, greater for preparations of the enzyme from shark skeletal muscle compared to beef heart. The low temperature near-infrared magnetic circular dichroism spectrum of the fully oxidized shark enzyme is not pH dependent in the experimental range, indicating the sensitivity of the visible region electronic spectrum to variation in pH to be due principally to changes at the heme a3-CuB chromophore. The results are discussed in relation to proposed mechanisms of proton translocation in cytochrome c oxidase.

Animals↗

2-Phenyl-4-(aminomethyl)imidazoles as potential antipsychotic agents. Synthesis and dopamine D2 receptor binding.

A series of 2-phenyl-4-(aminomethyl)imidazoles were designed as conformationally restricted analogs of the dopamine D2 selective benzamide antipsychotics. The title compounds were synthesized and tested for blockade of [3H]YM-09151 binding in cloned African green monkey dopamine D2 receptor preparations. The binding affinity data thus obtained were compared against that of the benzamides and a previously described series of 2-phenyl-5-(aminomethyl)-pyrroles.

Animals↗

The haem b558 component of the cytochrome bd quinol oxidase complex from Escherichia coli has histidine-methionine axial ligation.

The cytochrome bd ubiquinol oxidase from Escherichia coli is induced when the bacteria are cultured under microaerophilic or low-aeration conditions. This membrane-bound respiratory oxidase catalyses the two-electron oxidation of ubiquinol and the four-electron reduction of dioxygen to water. The oxidase contains three haem prosthetic groups: haem b558, haem b595 and haem d. Haem d is the oxygen binding site, and it is likely that haem d and b595 form a bimetallic site in the enzyme. Haem b558 has been previously characterized spectroscopically as being low spin and has been shown to be located within subunit I (CydA) of this two-subunit enzyme. It is likely that haem b558 is associated with the quinol oxidation site, which has also been shown to be within subunit I. In a previous effort to locate the specific amino acids axially ligated to haem b558, all six histidines within subunit I were altered by site-directed mutagenesis. Only one, histidine-186, was identified as a likely ligand to haem b558. Hence it was suggested that haem b558 could not have bis(histidine) ligation. In the current work, a combination of low-temperature near-infrared magnetic circular dichroism (NIR-MCD) and EPR spectroscopies have been employed to identify the nature of the haem b558 axial ligands. The NIR-MCD spectrum at cryogenic temperatures is dominated by the low-spin haem b558 component of the complex, and the low-energy band near 1800 nm is strong evidence for histidine-methionine ligation. It is concluded that haem b558 is ligated to histidine-186 plus one of the methionines located within subunit I of the oxidase.

Bacterial Proteins↗

Measurement of the spin concentration of metalloprotein samples from saturation-magnetization data with particular reference to cytochrome c oxidase.

A protocol for obtaining high-quality saturation-magnetization data from metalloprotein samples, employing a superconducting quantum interference device (SQUID) magnetometer, has previously been reported [E. P. Day, T. A. Kent, P. A. Lindahl, E. Münck, W. H. Orme-Johnson, H. Roder and A. Roy (1987) Biophys. J. 52, 837-853 and E. P. Day (1993) Methods Enzymol. 227, 437-463]. Following studies of several dozen different metalloprotein derivatives, the methodology has been further refined, particularly in the area of sample preparation. The details of the sample-handling procedures now in use are described, and moreover, the critical issue of verifying that contamination by paramagnetic impurities remains insignificant is considered. Importantly, it is shown that an independent determination of the quantity of paramagnetic sample present in the magnetometer is undesirable. Much more reliable parameters concerning the ground-state magnetic properties of the system under study are obtained if enough saturation-magnetization data are collected to enable the spin concentration to be determined during the subsequent fitting procedure. As proof of the validity of this method, the results of magnetization studies on ferricytochrome c, ferrocytochrome c and the benzohydroxamic acid adduct of horseradish peroxidase are presented. The ability of saturation-magnetization measurements to routinely determine spin concentration to within +/- 4% of accepted values is firmly established. In addition, a saturation-magnetization study has been performed on resting and fully reduced derivatives of cytochrome c oxidase. These results provide an illustration of the usefulness of the technique in probing some systems which have proved difficult to study by other methods. The increased difficulties inherent in obtaining meaningful data from these cytochrome c oxidase and other integer spin systems are delineated.

Animals↗

Experimental allergic encephalomyelitis in non-human primates: MRI and MRS may predict the type of brain damage.

Volume-localized proton spectroscopy and T2-weighted MRI were performed on 23 monkeys with experimental allergic encephalomyelitis (EAE). The purpose of this study was to determine the relationships between temporal changes in lesion activity (measured on T2-weighted MRI), MRS [N-acetyl aspartate (NAA), creatine (CR), choline (CHO)], and the histologic definition of disease determined post-mortem. Animals were scanned in the same areas of the brain once a week before and after sensitization to myelin basic protein (BP). Histologic lesion types were predicted by a combination of preceding MRI and MRS measurements. Acutely fatal EAE lesions were large and monophasic as visualized by MRI, and increased CHO (p < 0.02, n = 16) and CHO/CR ratio (p < 0.001, n = 16) were detected by MRS at disease onset. Chronic EAE lesions were preceded by multiple inflammatory attacks as visualized by MRI and consistently low levels of NAA (p < 0.02, n = 13) and NAA/CR (p < 0.01, n = 13) which occurred after the initial attack. MRI negative brain regions (from animals that were sensitized to BP) were associated with low CHO/CR (p < 0.1, n = 5). The temporal correlation of MRI lesion activity and absolute MRS proton metabolites shows promise for predicting the subsequent duration and histologic type of lesions in EAE in non-human primates.

Animals↗

Rapid identification of elaiophylin and geldanamycin in Streptomyces fermentation broths using CPC coupled with a photodiode array detector and LC-MS methodologies.

During the course of screening microbial broth extracts in various high through-put bioassays (eg receptor binding or enzyme inhibition), several actinomycete cultures were discovered to produce active metabolites. The natural products elaiophylin and/or geldanamycin are produced by several Streptomyces violaceusniger strains, and the bioactivity of the extracts from these cultures was frequently associated with the fractions containing these metabolites. CPC coupled to a photodiode array detector and LC-MS techniques were applied to these broth extracts to ascertain rapidly when these natural products were present. These methodologies allowed us to identify the metabolites quickly in the crude extract, and the application demonstrated further the utility of CPC-photodiode array detection and LC-MS as powerful, initial analytical tools in analyses of the complex metabolite profiles produced by microorganisms.

Anti-Bacterial Agents↗

Monomeric ferric heme peptide derivatives: model systems for hemoproteins.

Electron paramagnetic resonance spectra of a number of ferric heme peptide derivatives, in aqueous-detergent and various aqueous-alcohol solvent mixtures, have been obtained using samples in the concentration range 0.1-1.0 mM. Some of these were clearly monomeric, homogeneous, mixed-ligand adducts, entirely suitable for use as model systems for hemoprotein spectroscopic studies. As anticipated, the measured EPR parameters were largely independent of solvent environment. Surprisingly, micellar preparations of ferric heme undecapeptide in mildly alkaline solution showed no evidence for the formation of a hydroxide adduct, contrary to a previous report [S. Mazumdar, O. K. Medhi and S. Mitra, Inorg. Chem. 30 700 (1991)].

Amino Acid Sequence↗

Experimental allergic encephalomyelitis in non-human primates: diffusion imaging of acute and chronic brain lesions.

Diffusion imaging and T2-weighted magnetic resonance imaging were performed on 16 monkeys with experimental allergic encephalomyelitis (EAE), a model of the human demyelinating disease MS. The purpose of this study was to determine whether local changes in diffusion image intensity could be correlated with the formation of acute and chronic demyelinating lesions. Diffusion image analysis was restricted to the internal capsule of the brain because of its anatomic orientation of fiber pathways. Acute inflammatory EAE lesions were large and monophasic, as visualized by T2-weighted MRI, and were accompanied by a decrease in the diffusion MR image signal with the diffusion-sensitizing gradient in all three orthogonal directions (n = 27 brain regions, P < 0.005). Chronic demyelinating lesions were preceded by multiple inflammatory attacks, as visualized by MRI, and by a decrease in diffusion MR image signal with the diffusion-sensitizing gradient in the two orthogonal directions perpendicular to the fibers of the internal capsule (n = 18 brain regions, P < 0.005). However, for the chronic group, there was no significant change in the diffusion MR image signal with diffusion-sensitizing gradient parallel to the fibers of the internal capsule at the terminal scan, suggesting little change in the water diffusion within the nerve fibers. These results suggest that diffusion imaging holds promise for measuring subtle changes in water diffusion due to different types of brain damage.

Acute Disease↗

Drugs and aggression: correlations, crime and human manipulative studies and some proposed mechanisms.

Violence and drugs seem to mix readily. In this paper, relevant correlational studies are briefly reviewed and methodological issues are discussed. With a focus on alcohol, facts pointing to some type of causal relationship are presented both from crime and laboratory manipulative studies. Dose and rate-dependent anxiolytic, psychomotor stimulant and alteration in inhibitory and problem-solving cognitive functions are each in turn seen as precipatory to aggression. Drugs other than alcohol which interact with these systems are also discussed.

Aggression↗

The use of near-infrared charge-transfer transitions of low-spin ferric chlorins in axial ligand assignment.

The near-infrared magnetic circular dichroism spectra of some low-spin derivatives of ferric-octaethylchlorin substituted myoglobin have been recorded at cryogenic temperatures. The spectra, which include some of the lowest energy charge-transfer transitions ever observed for hemes, are clearly dependent upon the nature of the axial ligands present. While the results indicate that such spectra may have some practical utility in axial ligand assignment, as is now quite common practice for iron-porphyrin systems, there are some severe practical limitations to this protocol documented in the case of iron-chlorins.

Apoproteins↗

Identification of the axial heme ligands of cytochrome b556 in succinate: ubiquinone oxidoreductase from Escherichia coli.

Electron paramagnetic resonance (EPR) and near-infrared magnetic circular dichroism (MCD) have been used to identify the ligands to the cytochrome b556 component of succinate: ubiquinone oxidoreductase (succinate dehydrogenase) from Escherichia coli. The 'highly axial low spin' (HALS) EPR spectrum suggests bis(histidine) ligation of the heme with the histidines in a staggered configuration. The near-infrared MCD spectrum exhibits a low energy maximum at 1600 nm which is also clearly indicative of bis(histidine) ligation of the heme iron. The data unambiguously demonstrate that the heme b556 is ligated to E. coli succinate dehydrogenase via two histidines.

Binding Sites↗

HIV and tuberculosis infection in San Francisco's homeless adults. Prevalence and risk factors in a representative sample.

OBJECTIVE: To determine the prevalence and risk factors for human immunodeficiency virus (HIV) and tuberculosis (TB) infection and investigate the relationship between these two infections in homeless adults. DESIGN: Cross-sectional study. SETTING: Inner-city shelters and free meal programs. PARTICIPANTS: A representative sample of 1226 adults (> or = 18 years) were enrolled from community sites. MAIN OUTCOME MEASURES: Serum HIV-1 antibody status and tuberculin skin test reactivity. RESULTS: Human immunodeficiency virus seroprevalence was 8.5% (95% confidence interval [CI], 7.0% to 10.1%) and the prevalence of TB infection was 32% (95% CI, 30% to 37%). Nineteen percent of the HIV-seropositive subjects had positive tuberculin skin tests. Independent risk factors for HIV infection included younger age, black race, male homosexual contact, injection drug use, use of injection drugs in shooting galleries, and selling sex. Tuberculosis infection was associated with the duration of homelessness and living in crowded shelters or single-room-occupancy hotels. Injection drug use, a risk factor for HIV, was also a risk factor for TB, with a particularly strong association in women. No evidence of an association between TB and HIV infection was found, even after accounting for anergy. CONCLUSIONS: The homeless population in the United States should be considered a group at high risk for HIV infection and TB. Given the constellation of risk factors present, the high prevalence of infection, and lack of access to medical services, we anticipate that these communicable diseases in this population will represent a growing public health problem.

Adult↗