Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0149958 (complex partial seizures)
 2,563 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We recently developed a single photon radioluminescence (SPR) technique to measure submicroscopic distances in biological samples [Bicknese et al., and Shahrokh et al., Biophys. J., 63 (1992) 1256-1279]. SPR arises from the excitation of a fluorophore by the energy deposited from a slowing beta decay electron. The purpose of this study was to detect 3H2O molecules near tryptophan residues in proteins by tryptophan SPR. To detect small SPR signals, a sample compartment with reflective ellipsoidal optics was constructed, and amplified signals from a cooled photomultiplier were resolved by pulse-height analysis. A Monte Carlo calculation was carried out to quantify the relationship between SPR signal and 3H2O-tryptophan proximity. Measurements of tryptophan SPR were made on aqueous tryptophan; dissolved melittin (containing a single tryptophan); native and denatured aldolase; dissolved aldolase, monellin, and human serum albumin; and the integral membrane proteins CHIP28 (containing a putative aqueous pore) and MIP26 using 3H2O or the aqueous-phase probe 3H-3-O-methylglucose (OMG). After subtraction of a Bremsstrahlung background signal, the SPR signal from aqueous tryptophan (cps.microCi-1 mumol-1 +/- SE) was 8.6 +/- 0.2 with 3H2O and 7.8 +/- 0.3 with 3HOMG (n = 8). With 3H2O as donor, the SPR signal (cps.microCi-1 mumol-1) was 9.0 +/- 0.3 for monomeric melittin in low salt (trytophan exposed) and 4.6 +/- 0.8 (n = 9) for tetrameric melittin in high salt (tryptophans buried away from aqueous solution). The ratio of SPR signal obtained for aldolase under denaturing conditions of 8 M urea (fluorophores exposed) versus non-denaturing buffer (fluorophores buried) was 1.53 +/- 0.07 (n = 6). Ratios of SPR signals normalized to fluorescence intensities for monellin, aldolase, and human serum albumin, relative to that for d-tryptophan, were 1.42, 1.09, and 1.04, indicating that the cross-section for excitation of fluorophores in proteins is greater than that for tryptophan in solution. For the CHIP28 and MIP26 proteins in membranes, the ratio of SPR signal obtained with 3H2O versus 3HOMG was 1.35 +/- 0.13 (CHIP28, n = 5) and 0.99 +/- 0.02 (MIP26). These data are consistent with the existence of an aqueous channel through CHIP28 that excludes small solutes. We conclude that tryptophan radioluminescence in proteins is measurable and provides unique information about the presence of local aqueous compartments.
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PMID:Detection of water proximity to tryptophan residues in proteins by single photon radioluminescence. 774 62

Exposure of proteins to ONOO- (fatty acid-free bovine serum albumin (BSA) and histones, 10 mg/ml) was accompanied by light emission which could be detected using a photon counter. Light emission upon addition of ONOO- to either histones or BSA increased linearly with ONOO- concentration at a rate of 50 +/- 4 and 66 +/- 4 cps/(mg protein.mM ONOO-), respectively (averages+SE). Bicarbonate (25 mM) increased ONOO(-)-dependent BSA chemiluminescence approximately 3-fold above baseline (221 +/- 6 cps/(mg protein.mM ONOO-)). The peak of peroxynitrite-dependent light emission was around 40-fold higher than when 1 mM tert-butyl-hydroperoxide (t-BOOH) and 1.6 microM hemin were used as oxidants. Fatty acid-containing BSA (0.04-0.08%) emitted 3.4-fold more light than pure BSA. Chemiluminescence increased with pH, being 4.5-fold higher at pH 8.8 than at pH 6.0. However, the half-life of emissive species did not change with pH, suggesting that the process leading to the formation of electronically excited states is the same at all pHs. Tryptophan or N-acetyltyrosine oxidation by ONOO- was accompanied by chemiluminescence (130 +/- 10 and 14 +/- 3 cps/(mg amino acid.mM ONOO-), respectively). Exposure of DNA or isolated nucleotides to either t-BOOH/hemin or ONOO- was not accompanied by light emission. Leptomonas seymouri (an insect parasite used as a model of intact cells) exposed to ONOO- emitted 3700 +/- 400 cps/(mg protein.mM ONOO-), compared to 55 +/- 3 cps/(mg protein.mM peroxide) when t-BOOH was used as oxidant. While chemiluminescence of L. seymouri exposed to ONOO- increased measured at concentrations as low as 30 microM, carbonyl formation (from protein oxidation) and thiobarbituric acid-reactive substances (lipid peroxidation) could be measured only if cells were exposed to initial ONOO- larger than 700 microM. Spectral analysis suggests that excited carbonyls (emission wavelength 340-450 nm) are not produced in high proportions. A substantial amount of light is generated above 500 nm, part of which could come from triplet states of tryptophan and tyrosine.
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PMID:Peroxynitrite-dependent chemiluminescence of amino acids, proteins, and intact cells. 789 45

The kynurenine pathway metabolites, quinolinic acid (QUIN) and L-kynurenine are convulsants, whereas kynurenic acid (KYNA) is an antagonist of excitatory amino acid receptors. Imbalances in the concentrations of these metabolites have been implicated in the etiology of human seizure disorders. In the present study, L-kynurenine and QUIN concentrations in both cerebrospinal fluid (CSF) and serum were reduced in patients with intractable complex partial seizures (CPS) in both the postictal period (15-75 min after a seizure) and the interictal period (absence of seizure for > 24 h) as compared with neurologically normal control subjects. Linear regression analyses and analysis of covariance showed that the reductions in serum QUIN and L-kynurenine were correlated to blood antiepileptic medication. L-Tryptophan (L-TRP) levels also tended to be lower in both CSF and serum of the seizure patients. CSF KYNA and serum 3-hydroxykynurenine concentrations were not affected in seizure patients, whereas serum levels of KYNA were reduced. 3-Hydroxykynurenine was not detected in the CSF of either control or seizure patients. The results do not support a role for a generalized reduction in KYNA concentrations or an increased ratio of QUIN:KYNA, or increases in CSF L-kynurenine in initiation and maintenance of intractable CPS humans.
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PMID:Kynurenine pathway metabolites in cerebrospinal fluid and serum in complex partial seizures. 815 42

The genetic diversity of Human Immunodeficiency Virus type-1(HIV-1) has been shown to affect the performance of Nucleic Acid Testing (NAT) of Human Immunodeficiency Virus type-1. Although, majority NAT assays were designed to detect the conserved regions of HIV-1 mutations at the primer or probe binding regions may lead to false negatives. In this study, we evaluated the feasibility of detecting two genomic targets for enhanced sensitivity. A total of 180 tests using HIV-1 VQA RNA quantitation standard, 240 tests using EQAPOL HIV-1 viral diversity subtype panel, and 30 clinical plasma samples from Cameroon were evaluated. The analysis was based on probit and hit rate. The genomic targets LOD estimated by PROBIT for the gag target was 118 cps/ml (95%CI 64 cps/ml lower bound), Pol or POL/LTR was at 40 cps/ml (95%CI 17, 16 cps/ml), LTR 45 cps/ml (95%CI 20 cps/ml lower bound), and Gag/LTR at 67.8 cps/ml (95%CI 32 cps/ml lower bound). For HIV-1 subtypes the overall reactivity was 55-100% when tested at 100 and 1000 cps/ml and combination of genomic targets detection increased the reactivity to 100%. The plasma samples evaluation showed LTR or pol/LTR combination yielded higher sensitivity for patients with lower viral load (<40 cps/ml). We conclude that detection of two HIV-1 genomic targets improved sensitivity for detection of genetically diverse HIV-1 strains.
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PMID:High sensitivity detection of HIV-1 using two genomic targets compared with single target PCR. 2657 93