Complete stereospecific repair of a synthetic dinucleotide spore photoproduct by spore photoproduct lyase.

Spore photoproduct lyase (SP lyase), a member of the radical S-adenosylmethionine superfamily of enzymes, catalyzes the repair of 5-thyminyl-5,6-dihydrothymine [spore photoproduct (SP)], a type of UV-induced DNA damage unique to bacterial spores. The anaerobic purification and characterization of Clostridium acetobutylicum SP lyase heterologously expressed in Escherichia coli, and its catalytic activity in repairing stereochemically defined synthetic dinucleotide SPs was investigated. The purified enzyme contains between 2.

An efficient deprotection of N-trimethylsilylethoxymethyl (SEM) groups from dinucleosides and dinucleotides.

A convenient and efficient method for deprotection of N-(trimethyl)silylethoxymethyl (SEM) groups from thymidine dinucleoside and dinucleotide has been achieved. The SEM groups were easily removed in excellent yields from protected nucleosides, dinucleosides, and dinucleotides.

Equipoise among recanalization strategies.

Modern acute ischemic stroke therapy is based on the premise that recanalization and subsequent reperfusion are essential for the preservation of brain tissue and favorable clinical outcomes. We outline key issues that we think underlie equipoise regarding the comparative clinical efficacy of IV recombinant tissue-type plasminogen activator (rt-PA) and intra-arterial (IA) reperfusion therapies for acute ischemic stroke. On the one hand, IV rt-PA therapy has the benefit of speed with presumed lower rates of recanalization of large artery occlusions as compared to IA methods.

The relationship between smoking and replicated sequence variants on chromosomes 8 and 9 with familial intracranial aneurysm.

Background And Purpose: The purpose of this study was to replicate the previous association of single nucleotide polymorphisms (SNPs) with risk of intracranial aneurysm (IA) and to examine the relationship of smoking with these variants and the risk of IA.

Methods: White probands with an IA from families with multiple affected members were identified by 26 clinical centers located throughout North America, New Zealand, and Australia. White control subjects free of stroke and IA were selected by random digit dialing from the Greater Cincinnati population.

Chemoselective deprotection of triethylsilyl ethers.

An efficient and selective method was developed for the deprotection of triethylsilyl (TES) ethers using formic acid in methanol (5-10%) or in methylene chloride 2-5%) with excellent yields. TES ethers are selectively deprotected to the corresponding alcohols in high yields using formic acid in methanol under mild reaction conditions. Other hydroxyl protecting groups like t-butyldimethylsilyl (TBDMS) remain unaffected.

The antiviral protein viperin is a radical SAM enzyme.

Viperin, an interferon-inducible antiviral protein, is shown to bind an iron-sulfur cluster, based on iron analysis as well as UV-Vis and electron paramagnetic resonance spectroscopic data. The reduced protein contains a [4Fe-4S](1+) cluster whose g-values are altered upon addition of S-adenosylmethionine (SAM), consistent with SAM coordination to the cluster. Incubation of reduced viperin with SAM results in reductive cleavage of SAM to produce 5'-deoxyadenosine (5'-dAdo), a reaction characteristic of the radical SAM superfamily.

Thromboembolic events with recombinant activated factor VII in spontaneous intracerebral hemorrhage: results from the Factor Seven for Acute Hemorrhagic Stroke (FAST) trial.

Background And Purpose: Patients with intracerebral hemorrhage have a high risk of thromboembolic events (TEs) due to advanced age, hypertension, atherosclerosis, diabetes, and immobility. Use of recombinant activated factor VII (rFVIIa) could increase TEs in high-risk patients. Factor Seven for Acute Hemorrhagic Stroke (FAST) trial data were reviewed to define the frequency of and risk factors for TE with rFVIIa.

Identification and characterization of a novel member of the radical AdoMet enzyme superfamily and implications for the biosynthesis of the Hmd hydrogenase active site cofactor.

The genetic context, phylogeny, and biochemistry of a gene flanking the H(2)-forming methylene-H(4)-methanopterin dehydrogenase gene (hmdA), here designated hmdB, indicate that it is a new member of the radical S-adenosylmethionine enzyme superfamily. In contrast to the characteristic CX(3)CX(2)C or CX(2)CX(4)C motif defining this family, HmdB contains a unique CX(5)CX(2)C motif.

Good clinical outcome after ischemic stroke with successful revascularization is time-dependent.

Background: Trials of IV recombinant tissue plasminogen activator (rt-PA) have demonstrated that longer times from ischemic stroke symptom onset to initiation of treatment are associated with progressively lower likelihoods of clinical benefit, and likely no benefit beyond 4.5 hours. How the timing of IV rt-PA initiation relates to timing of restoration of blood flow has been unclear.

Multi-modal examination of psychological and interpersonal distinctions among MPI coping clusters: a preliminary study.

Unlabelled: The Multidimensional Pain Inventory (MPI) is a widely used instrument to characterize distinct psychosocial subgroups of patients with chronic pain: Adaptive (AC), Dysfunctional (DYS), and Interpersonally Distressed (ID). To date, several questions remain about the validity and distinctiveness of the patient clusters, and continued scientific attention has strongly been recommended. It is unclear if AC patients experience better adjustment or merely present themselves favorably.

The iron-sulfur cluster of pyruvate formate-lyase activating enzyme in whole cells: cluster interconversion and a valence-localized [4Fe-4S]2+ state.

Pyruvate formate-lyase activating enzyme (PFL-AE) catalyzes the generation of a catalytically essential glycyl radical on pyruvate formate-lyase (PFL). Purified PFL-AE contains an oxygen-sensitive, labile [4Fe-4S] cluster that undergoes cluster interconversions in vitro, with only the [4Fe-4S](+) cluster state being catalytically active. Such cluster interconversions could play a role in regulating the activity of PFL-AE, and thus of PFL, in response to oxygen levels in vivo.

Hydrogenase cluster biosynthesis: organometallic chemistry nature's way.

It has been over a decade now since it was revealed that the metal containing active sites of hydrogenases possess carbonyl and cyanide ligands bound to iron. The presence of these ligands in hydrogenases came as a surprise and to-date these ligands have not been observed to be associated with any other enzymatic metallocenter. The elucidation of the structures of these unique metalloenzymes and their associated metal clusters created opportunity for a number of different lines of research.

Temporal trends in public awareness of stroke: warning signs, risk factors, and treatment.

Background And Purpose: Delay in seeking medical attention after stroke symptom onset is the most important reason for low rates of thrombolytic use for ischemic stroke (IS) in the United States. This may be related to poor recognition of stroke symptoms, or to lack of awareness of time-sensitive stroke treatments. We describe public knowledge of t-PA as a treatment for IS, as well as changes over time in knowledge of stroke warning signs (WS) and risk factors (RF).

Inspiratory airflow dynamics during sleep in irritable bowel syndrome: a pilot study.

Purpose: This study is a preliminary test of the hypothesis that the pathophysiology of irritable bowel syndrome (IBS) derives from pharyngeal collapse during sleep.

Materials And Methods: We studied inspiratory airflow dynamics during sleep in 12 lean females with IBS and 12 healthy female controls matched for age and obesity. A standard clinical polysomnogram (airflow measured with a nasal/oral pressure catheter) was performed to assess the impact of pharyngeal collapse on the participants' natural sleep.

Global differences in patient characteristics, case management and outcomes in intracerebral hemorrhage: the Factor Seven for Acute Hemorrhagic Stroke (FAST) trial.

Background: The outcomes after stroke vary considerably between countries, yet the extent of the variation after intracerebral hemorrhage (ICH) remains unknown. This study examines differences in outcomes after ICH in a recent multinational trial, and explores the effect of differences in patient severity and case management for the variations observed.

Methods: Factor Seven for Acute Hemorrhagic Stroke was a randomized, multinational, double-blind, placebo-controlled trial conducted between May 2005 and February 2007 at 122 sites in 22 countries.

Activation of HydA(DeltaEFG) requires a preformed [4Fe-4S] cluster.

The H-cluster is a complex bridged metal assembly at the active site of [FeFe]-hydrogenases that consists of a [4Fe-4S] subcluster bridged to a 2Fe-containing subcluster with unique nonprotein ligands, including carbon monoxide, cyanide, and a dithiolate ligand of unknown composition. Specific biosynthetic gene products (HydE, HydF, and HydG) responsible for the biosynthesis of the H-cluster and the maturation of active [FeFe]-hydrogenase have previously been identified and shown to be required for the heterologous expression of active [FeFe]-hydrogenase [Posewitz, M. C.

Validation of the MPI patient profiles by partners and healthcare providers.

The Multidimensional Pain Inventory (MPI) is one of the most widely used instruments to assess patients' coping with chronic pain. It provides a psychosocial classification system that categorizes patients into three coping styles: Adaptive, Dysfunctional, and Interpersonally Distressed. To date, comprehensive information about the validity of the MPI taxonomy obtained from informants other than the patient has been unavailable.

Emergency medical services use by stroke patients: a population-based study.

Objectives: Emergency medical services (EMS) use by stroke patients varies from 38% to 65%. In an epidemiological study, we determined the proportion of stroke patients who used EMS, hypothesizing that demographics, stroke severity, stroke type, and location at stroke onset would be associated with EMS use.

Methods: Stroke and transient ischemic attack patients were identified in a population of 1.

Density and shape as CT predictors of intracerebral hemorrhage growth.

Background And Purpose: Intracerebral hemorrhage (ICH) growth predicts mortality and functional outcome. We hypothesized that irregular hematoma shape and density heterogeneity, reflecting active, multifocal bleeding or a variable bleeding time course, would predict ICH growth.

Methods: Three raters examined baseline sub-3-hour CT brain scans of 90 patients in the placebo arm of a Phase IIb trial of recombinant activated Factor VII in ICH.