PubMed Health⌕ Search

Biomedical subjects

T Henry

Publications and source records attributed to T Henry.

At least 19 recordsLinked to original sources
PubMed2005

Identification of Salmonella functions critical for bacterial cell division within eukaryotic cells.

Salmonella typhimurium multiplication inside eukaryotic host cells is critical for virulence. Salmonella typhimurium strain SL1344 appears as filaments upon growth in macrophages and MelJuSo cells, a human melanoma cell line, indicating a specific blockage in the bacterial cell division process. Several studies have investigated the host cell response impairing bacterial division. However, none looked at the bacterial factors involved in inhibition of Salmonella division inside eukaryotic cells. We show here that blockage in the bacterial division process is sulA-independent and takes place after FtsZ-ring assembly. Salmonella typhimurium genes in which mutations lead to filamentous growth within host cells were identified by a large scale mutagenesis approach on strain 12023, revealing bacterial functions crucial for cell division within eukaryotic cells. We finally demonstrate that SL1344 filamentation is a result of hisG mutation, requires the activity of an enzyme of the histidine biosynthetic pathway HisFH and is specific for the vacuolar environment.

Aminohydrolases↗
PubMed2001

Epileptic seizures may begin hours in advance of clinical onset: a report of five patients.

Mechanisms underlying seizure generation are traditionally thought to act over seconds to minutes before clinical seizure onset. We analyzed continuous 3- to 14-day intracranial EEG recordings from five patients with mesial temporal lobe epilepsy obtained during evaluation for epilepsy surgery. We found localized quantitative EEG changes identifying prolonged bursts of complex epileptiform discharges that became more prevalent 7 hr before seizures and highly localized subclinical seizure-like activity that became more frequent 2 hr prior to seizure onset. Accumulated energy increased in the 50 min before seizure onset, compared to baseline. These observations, from a small number of patients, suggest that epileptic seizures may begin as a cascade of electrophysiological events that evolve over hours and that quantitative measures of preseizure electrical activity could possibly be used to predict seizures far in advance of clinical onset.

Action Potentials↗
PubMed2001

Availability of on-site catheterization and clinical outcomes in patients receiving fibrinolysis for ST-elevation myocardial infarction.

AIMS: To compare management and clinical outcomes in hospitals stratified by the availability of on-site catheterization in InTIME-II, a multicentre trial comparing alteplase with lanoteplase for acute myocardial infarction. METHODS AND RESULTS: We studied 15,078 patients enrolled in 35 countries and 855 hospitals. Thirty-one percent of hospitals had 24-h, 25% day-only, and 44% no on-site catheterization facilities. Rates of cardiac angiography (57%, 38%, 26%) and revascularization (37%, 21%, 17%) were higher in hospitals with increasing access to on-site facilities(P<0.0001). The presence of a 24-h on-site facility was the strongest predictor of angiography during the index admission (odds ratio 4.17, 95% CI 3.85-4.54). There were no major differences in patient outcomes at 30 days when hospitals were stratified by availability of on-site catheterization. Adjusted 1-year mortality was similar between groups of hospitals (odds ratio for day-only 0.94 [0.80-1.09] and odds ratio for no availability 0.95 [0.83-1.10] compared to hospitals with 24-h facilities). CONCLUSIONS: There is a marked variation in procedure use by the availability of on-site catheterization with no major differences in patient outcomes. There is a need for additional randomized trials in the current era to address both the appropriate selection of patients and timing of invasive procedures in ST-elevation acute myocardial infarction.

Adolescent↗
PubMed2001

Delivery of multiple epitopes by recombinant detoxified adenylate cyclase of Bordetella pertussis induces protective antiviral immunity.

CyaA, the adenylate cyclase toxin from Bordetella pertussis, can deliver its N-terminal catalytic domain into the cytosol of a large number of eukaryotic cells and particularly into professional antigen-presenting cells. We have previously identified within the primary structure of CyaA several permissive sites at which insertion of peptides does not alter the ability of the toxin to enter cells. This property has been exploited to design recombinant CyaA toxoids capable of delivering major histocompatibility complex (MHC) class I-restricted CD8(+) T-cell epitopes into antigen-presenting cells and to induce specific CD8(+) cytotoxic T-lymphocyte (CTL) responses in vivo. Here we have explored the capacity of the CyaA vector carrying several different CD8(+) T-cell epitopes to prime multiple CTL responses. The model vaccine consisted of a polyepitope made of three CTL epitopes from lymphocytic choriomeningitis virus (LCMV), the V3 region of human immunodeficiency virus gp120, and chicken ovalbumin, inserted at three different sites of the catalytic domain of genetically detoxified CyaA. Each of these epitopes was processed on delivery by CyaA and presented in vitro to specific T-cell hybridomas. Immunization of mice by CyaA toxoids carrying the polyepitope lead to the induction of specific CTL responses for each of the three epitopes, as well as to protection against a lethal viral challenge. Moreover, mice primed against the vector by mock CyaA or a recombinant toxoid were still able to develop strong CTL responses after subsequent immunization with a recombinant CyaA carrying a foreign CD8(+) CTL epitope. These results highlight the potency of the adenylate cyclase vector for induction of protective CTL responses with multiple specificity and/or broad MHC restriction.

Adenylyl Cyclases↗
PubMed2001

Emergence in Asia of foot-and-mouth disease viruses with altered host range: characterization of alterations in the 3A protein.

In 1997, an epizootic in Taiwan, Province of China, was caused by a type O foot-and-mouth disease virus which infected pigs but not cattle. The virus had an altered 3A protein, which harbored a 10-amino-acid deletion and a series of substitutions. Here we show that this deletion is present in the earliest type O virus examined from the region (from 1970), whereas substitutions surrounding the deletion accumulated over the last 29 years. Analyses of the growth of these viruses in bovine cells suggest that changes in the genome in addition to the deletion, per se, are responsible for the porcinophilic properties of current Asian viruses in this lineage.

Amino Acid Sequence↗
PubMed2000

Optimum percutaneous transluminal coronary angioplasty compared with routine stent strategy trial (OPUS-1): a randomised trial.

BACKGROUND: Whether routine implantation of coronary stents is the best strategy to treat flow-limiting coronary stenoses is unclear. An alternative approach is to do balloon angioplasty and provisionally use stents only to treat suboptimum results. We did a multicentre trial to compare the outcomes of patients treated with these strategies. METHODS: We randomly assigned 479 patients undergoing single-vessel coronary angioplasty routine stent implantation or initial balloon angioplasty and provisional stenting. We followed up patients for 6 months to determine the composite rate of death, myocardial infarction, cardiac surgery, and target-vessel revascularisation. RESULTS: Stents were implanted in 227 (98.7%) of the patients assigned routine stenting. 93 (37%) patients assigned balloon angioplasty had at least one stent placed because of suboptimum angioplasty results. At 6 months the composite endpoint was significantly lower in the routine stent strategy (14 events, 6.1%) than with the strategy of balloon angioplasty with provisional stenting (37 events, 14.9%, p=0.003). The cost of the initial revascularisation procedure was higher than when a routine stent strategy was used (US$389 vs $339, p<0.001) but at 6 months, average per-patient hospital costs did not differ ($10,206 vs $10,490). Bootstrap replication of 6-month cost data showed continued economic benefit of the routine stent strategy. INTERPRETATION: Routine stent implantation leads to better acute and long-term clinical outcomes at a cost similar to that of initial balloon angioplasty with provisional stenting.

Adult↗
PubMed2000

Prospective long-term study of vagus nerve stimulation for the treatment of refractory seizures.

PURPOSE: To determine the long-term efficacy of vagus nerve stimulation (VNS) for refractory seizures. VNS is a new treatment for refractory epilepsy. Two short-term double-blind trials have demonstrated its safety and efficacy, and one long-term study in 114 patients has demonstrated a cumulative improvement in efficacy at 1 year. We report the largest prospective long-term study of VNS to date. METHODS: Patients with six or more complex partial or generalized tonic-clonic seizures enrolled in the pivotal EO5 study were prospectively evaluated for 12 months. The primary outcome variable was the percentage reduction in total seizure frequency at 3 and 12 months after completion of the acute EO5 trial, compared with the preimplantation baseline. Subjects originally randomized to low stimulation (active-control group) were crossed over to therapeutic stimulation settings for the first time. Subjects initially randomized to high settings were maintained on high settings throughout the 12-month study. RESULTS: The median reduction at 12 months after completion of the initial double-blind study was 45%. At 12 months, 35% of 195 subjects had a >50% reduction in seizures, and 20% of 195 had a >75% reduction in seizures. CONCLUSIONS: The efficacy of VNS improves during 12 months, and many subjects sustain >75% reductions in seizures.

Electric Stimulation Therapy↗
PubMed2000

Identification of Aspergillus species using internal transcribed spacer regions 1 and 2.

Aspergillus species are the most frequent cause of invasive mold infections in immunocompromised patients. Although over 180 species are found within the genus, 3 species, Aspergillus flavus, A. fumigatus, and A. terreus, account for most cases of invasive aspergillosis (IA), with A. nidulans, A. niger, and A. ustus being rare causes of IA. The ability to distinguish between the various clinically relevant Aspergillus species may have diagnostic value, as certain species are associated with higher mortality and increased virulence and vary in their resistance to antifungal therapy. A method to identify Aspergillus at the species level and differentiate it from other true pathogenic and opportunistic molds was developed using the 18S and 28S rRNA genes for primer binding sites. The contiguous internal transcribed spacer (ITS) region, ITS 1-5.8S-ITS 2, from referenced strains and clinical isolates of aspergilli and other fungi were amplified, sequenced, and compared with non-reference strain sequences in GenBank. ITS amplicons from Aspergillus species ranged in size from 565 to 613 bp. Comparison of reference strains and GenBank sequences demonstrated that both ITS 1 and ITS 2 regions were needed for accurate identification of Aspergillus at the species level. Intraspecies variation among clinical isolates and reference strains was minimal. Sixteen other pathogenic molds demonstrated less than 89% similarity with Aspergillus ITS 1 and 2 sequences. A blind study of 11 clinical isolates was performed, and each was correctly identified. Clinical application of this approach may allow for earlier diagnosis and selection of effective antifungal agents for patients with IA.

Aspergillosis↗
PubMed2000

Responses of seventh grade students to "do you have a partner with whom you would like to have a baby?".

This study investigated differences in demographic data, self-esteem, and coping skills for 225 students in Grade 7 who reported having a partner with whom they wanted to have a baby and 946 students who did not. Data were collected on the Rosenberg Self-esteem Scale, the Family Crisis-oriented Personal Evaluation Scale, and questions related to attitudes towards teen pregnancy and demographic data. The sample included 548 (46.8%) boys and 624 (53.2%) girls whose mean age was 13.2 yr. Students with a partner had significantly lower scores on the curriculum questions, self-esteem, and family coping skills, combined with higher scores in passivity. They indicated a desire to have a greater number of children, beginning by having their first child at a younger age and believed that having a baby improves a couple's relationship. Possible approaches may include effective teaching methods to overcome passivity through boosting self-confidence, goal-setting, and acquiring a purpose in life besides parenting a child.

Adolescent↗
PubMed1999

Plasmid-mediated expression of the UmuDC mutagenesis proteins in an Escherichia coli strain engineered for human cytochrome P450 1A2-catalyzed activation of aromatic amines.

The mutagenic actions of many chemicals depend on the activities of bacterial "mutagenesis proteins", which allow replicative bypass of DNA lesions. Genes encoding these proteins occur on bacterial chromosomes and plasmids, often in the form of an operon (such as umuDC or mucAB) encoding two proteins. Many bacterial strains used in mutagenicity testing carry mutagenesis protein genes borne on plasmids, such as pKM101. Our objective was to introduce mutagenesis protein function into Escherichia coli strain DJ4309. This strain expresses recombinant human cytochrome P450 1A2 and NADPH-P450 reductase and carries out the metabolic conversion of aromatic and heterocyclic amines into DNA-reactive mutagens. We discovered that many mutagenesis-protein plasmids severely inhibit the response of strain DJ4309 to 2-amino-3,4-dimethylimid-azo[4,5-f]quinoline (MeIQ), a typical heterocyclic amine mutagen. Among many plasmids examined, one, pGY8294, a pSC101 derivative carrying the umuDC operon, did not inhibit MeIQ mutagenesis. Strain DJ4309 pGY8294 expresses active mutagenesis proteins, as shown by its response to mutagens such as 1-nitropyrene and 4-nitroquinoline 1-oxide (4-NQO), and is as sensitive as the parent strain DJ4309 to P450-dependent mutagens, such as MeIQ and 1-aminopyrene.

Amines↗
PubMed1999

Examining an affect regulation model of substance abuse in schizophrenia. The role of traits and coping.

Comorbid substance use disorders occur frequently in schizophrenia with significant detrimental effects to clinical outcome. Unfortunately, attempts to identify factors associated with comorbid substance use disorders (beyond demographic characteristics such as gender) have not been successful. This study examined an affect regulation model of comorbid substance use in schizophrenia with a focus on personality traits and coping. It was hypothesized that maladaptive coping and the traits of negative affect (NA) and disinhibition (DIS), but not trait positive affect (PA), would be associated with greater substance use problems. Thirty-nine patients with schizophrenia or schizoaffective disorder completed measures of personality traits, coping, and negative consequences associated with substance use. Traits were differentially associated with coping in that NA and DIS, but not PA, were associated with maladaptive coping including the use of drugs and alcohol to cope with stress. Alternatively, PA, but not DIS or NA, was related to adaptive coping strategies. Individuals high in NA and endorsing the use of drugs and alcohol to cope reported the greatest number of negative consequences from substance use. This finding held after controlling for gender. These results are consistent with an affect regulation model of substance use and suggest the advantage of examining the role of affect, traits, and coping in understanding comorbid substance use in schizophrenia.

Adaptation, Psychological↗
PubMed1998

Effects of prior aspirin and anti-ischemic therapy on outcome of patients with unstable angina. TIMI 7 Investigators. Thrombin Inhibition in Myocardial Ischemia.

Both aspirin and beta-adrenergic blocking drugs have been shown to reduce the risk of death or acute myocardial infarction (AMI) in patients with unstable angina, but their effect during chronic use on the presentation of acute coronary syndromes is less well defined. Calcium antagonists and oral nitrates are also widely prescribed for patients with coronary disease, but their effect on presentation of acute myocardial ischemia is unknown. We retrospectively examined the effects of prior aspirin and anti-ischemic medical therapy on clinical events in 410 patients hospitalized for unstable angina. Ischemic pain occurred at rest for a duration of 5 to 60 minutes. During hospitalization, 97% of patients received aspirin and all received the direct thrombin inhibitor bivalirudin for at least 72 hours. Despite being older and more likely to have risk factors for coronary disease and poor outcome, patients receiving aspirin before admission were less likely to present with non-Q-wave AMI (5% vs 14% in patients not on aspirin, p = 0.004). Prior beta blocker, calcium antagonist, or nitrate administration did not appear to modify presentation as unstable angina or non-Q-wave AMI. In a multivariate model, the combined incidence of death, AMI not present at enrollment, or recurrent angina was best predicted by age (adjusted odds ratio [95% confidence interval] 2.38 [1.14 to 3.98]) and presence of electrocardiographic changes with pain on presentation (adjusted odds ratio 2.83 [1.50 to 5.35]) but was not related to prior or in-hospital medical therapy. Thus, aspirin but not anti-ischemic therapy before hospitalization of patients with unstable angina was associated with a decreased incidence of non-Q-wave AMI on admission.

Adrenergic beta-Antagonists↗
PubMed1998

Cooperative ligand binding by bovine phenol sulfotransferase.

Although several phenol sulfotransferases (PSTs) that metabolize hormones and xenobiotics have been purified and examined by steady state kinetic methods, little is known about ligand binding and subunit interactions in these enzymes. Inhibition of a purified recombinant homodimeric bovine PST by 2,6-dichloro-4-nitrophenol (DCNP) and pentachlorophenol (PCP) displayed very sharp titration curves that required modeling with Hill equations with slope factors of 2 and 3, respectively. This observation suggested positive cooperative ligand binding during catalytic turnover. The binding of PCP was also monitored by intrinsic protein fluorescence, which was quenched up to 36% upon saturation with the inhibitor. In the absence of 3'-phosphoadenosine-5'-phosphosulfate (PAPS), quenching curves were fit with the Hill equation and an interaction factor of 1. In contrast, inclusion of PAPS increased the association of PCP and resulted in positive cooperative binding with an interaction factor of 1.6-1.9. Whereas adenosine-3',5'-diphosphate (PAP) also facilitated cooperative binding of PCP, adenosine-5'-monophosphate (AMP) was not effective. This correlated to inhibition of PST by PAP, whereas AMP was not inhibitory up to 1 mM. Therefore, occupation of the PST nucleotide binding site(s) facilitates a subunit interaction that can promote subsequent binding of phenolic ligands.

Animals↗
PubMed1997

Ictal patterns in temporal lobe epilepsy recorded by epidural screw electrodes.

In a consecutive series of 11 patients with a history of medically refractory temporal lobe epilepsy, we studied the appearance of ictal patterns detected by epidural screw electrodes (ESE) placed in an effort to obviate depth electrode recording. All had prior scalp-sphenoidal monitoring with significant obscuration of ictal EEG by movement and muscle artifact. Six to 10 ESE were placed at bilateral temporal locations of the 10% system. Ictal findings in 4-15 partial seizures from 8 patients with mesiobasal (MBTLE) and 3 patients with neocortical (NCTLE) epilepsy were correlated with imaging and histology. Five of 8 patients with MBTLE had discrete high frequency discharges at onset, evolving within 10 s to focal theta at ESE, before appearing at scalp electrodes. All had Class IA outcome with mesial temporal sclerosis (MTS). Three of 8 patients with MBTLE and MTS had less discrete onsets, with Class 1A, 1B and 3A outcomes. Two patients with NCTLE had lesions; a grade II oligoastrocytoma with rhythmic delta at ESE and Class 4 outcome, and an anterior temporal cavernous angioma with variable onsets, some of which were high frequency, with a Class 1A outcome. The third NCTLE patient demonstrated focal theta as an ictal pattern, had no lesion and a Class 1A outcome. Ictal onsets may be well localized in selected patients by ESE. A majority of patients with MTS display well defined high frequency ictal discharges.

Adolescent↗
PubMed1997

Hydrogen peroxide supports human and rat cytochrome P450 1A2-catalyzed 2-amino-3-methylimidazo[4,5-f]quinoline bioactivation to mutagenic metabolites: significance of cytochrome P450 peroxygenase.

We show that the naturally occurring hydroperoxide hydrogen peroxide is highly effective in supporting the cytochrome P450 1A2 peroxygenase-catalyzed metabolic activation of the heterocyclic aromatic amine 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) to genotoxic metabolites. Mutagenicity was assessed by the Ames assay with Salmonella typhimurium strain YG1012 and an activation system consisting of hydroperoxides plus either 3-methylcholanthrene-induced rat liver microsomes (rP4501A) or human P450 1A2-containing microsomes (hP4501A2). The mutagenic response was dependent on the concentration of microsomal protein, IQ, and hydroperoxides. The addition of hydrogen peroxide or tert-butyl hydroperoxide to rP4501A greatly enhanced the yield of histidine prototrophic (His+) revertants. This increase was inhibited, in a concentration-dependent manner, by alpha-naphthoflavone, a P450 1A inhibitor. Hydrogen peroxide was the most effective peroxygenase cofactor, particularly with hP4501A2 (K(m) = 0.1 mM). The hydroperoxide-supported activation of IQ produced reactive intermediates which bound to 2'-deoxyguanosine; LC/MS analysis of the adducts revealed the same major (protonated) adduct at m/z = 464.4 as previously reported for the DNA adduct formed (in vivo or in vitro) by the mixed function-catalyzed bioactivation system. None of the peroxidase-catalyzed IQ metabolites (nitro-, azo-, or azoxy-IQ) were detected. In conclusion, hydrogen peroxide in the physiological/pathological concentration range may be able to support the metabolic activation of arylamines to genotoxic products through the cytochrome P450 peroxygenase pathway.

Animals↗
PubMed1997

Induction and prevention of squamous transformation of bronchial epithelial cells by phenolic compounds.

1. The exposure of cultured bovine bronchial epithelial cells to 2-naphthol and catechol (10-100 microM) induced a squamous phenotype and inhibited cell proliferation. Phenol and cresol did not have these effects at up to 100 microM. 2. These effects occurred below cytotoxic levels and cell proliferation resumed subsequent to removal of the exposures. 3. Induction of the squamous phenotype was antagonized by retinoic acid, a known morphogenic hormone for several airway epithelial cell culture model systems. 4. Purified recombinant bovine phenol sulphotransferase was used to ablate the antiproliferative and squamous inductive effects of catechol on the cultured airway epithelial cells.

Animals↗
PubMed1996

Isolation and characterization of a bovine gene encoding phenol sulfotransferase.

Phenol sulfotransferases (PST) esterify hydroxylated aromatic compounds with sulfate, and therefore play a role in the metabolism of xenobiotics. In this investigation, a bovine PST gene of 2372 bp was amplified from genomic DNA. Sequence overlap with the cognate cDNA revealed seven exons, with all introns containing GT/AG splicing donor/acceptor site. This product was subcloned into an SV40-based expression vector and transfected into WI-26 human lung fibroblasts. Immunoblot analyses revealed production of the anticipated 32-kDa protein, and the active enzyme displayed steady-state kinetic properties consistent with the enzyme characterized in bovine lung (apparent Km = 6.5 microM for 2-naphthol).

Amino Acid Sequence↗