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At least 595 records · Page 33Linked to original sources
PubMed2006

Global transcriptional effects of PEG-IFN-alpha and ribavirin on peripheral blood cells obtained from patients with chronic hepatitis C.

The global transcriptional profile during the first 4 weeks of treatment with pegylated interferon alfa (PEG-IFN-alpha) therapy for chronic hepatitis C (CHC) was evaluated. cDNA array technology was used to assess expression of 10,918 human genes in peripheral blood cells obtained from 17 CHC patients at days 0, 7, and 28 following treatment with PEG-IFN-alpha and ribavirin. Hierarchical average linkage clustering identified seven temporal profiles of differential expression comprising 148 genes. Gene expression profiles were comparable between the PEG-IFN-alpha-2a and PEG-IFN-alpha-2b therapy. Genes representing a broad range of molecular functions were differentially regulated with distinct temporal patterns of expression. The initial global response to interferon treatment appears to be a net up-regulation of genes, consistent with gene responses identified previously in vitro, though by 4 weeks an overall down-regulation of genes was observed. Novel transcription factors potentially involved in secondary gene regulation cascades, a potential dsRNA receptor and members of the ubiquitin signaling, including a novel predicted deubiquitinating peptidase were all identified as being up-regulated upon treatment with IFN. The overall findings provide new light on possible physiological effects of IFN-alpha and open new lines of investigations on the mode of action of PEG-IFN-alpha combination therapy.

Journal Article↗
PubMed2004

An economic evaluation of a European cohort from a multinational trial of linezolid versus teicoplanin in serious Gram-positive bacterial infections: the importance of treatment setting in evaluating treatment effects.

In a recent multinational trial, hospital resource use and total cost of treatment were compared between linezolid and teicoplanin for severe Gram-positive bacterial infections among 227 European hospitalised patients. The results show that the linezolid group had a 3.2-day (6.3 for linezolid versus 9.5 for teicoplanin groups) shorter mean intravenous antibiotic treatment duration. Certain baseline variables, particularly the inpatient location at enrolment and the presence of outpatient/home parenteral antibiotic therapy (OHPAT), had substantial effects on length of stay (LOS) and cost of treatment. After adjusting for the between-treatment difference in these two variables and other baseline variables, the results showed non-significant shorter LOS and lower mean total cost of treatment for the linezolid group among patients with no access to OHPAT.

Acetamides↗
PubMed2003

Outcome of liver transplantation for familial amyloidotic polyneuropathy.

Familial amyloidotic polyneuropathy (FAP) is an autosomal dominant disorder caused by mutation in the transthyretin gene. The most common mutation is substitution of valine for methionine at position 30 (MET30). Liver transplantation (LT) is the preferred treatment. After LT, although many patients show stabilization or improvement in the disease, adverse outcomes have been reported in those who have malnutrition, long-standing disease, and non-MET (NMET) mutations at position 30. Our aim is to compare survival and outcome of symptoms associated with FAP after LT in patients with MET30 and NMET30 mutations. Medical records of all patients who underwent LT for amyloidosis at our institution were reviewed to obtain demographic information and clinical features, such as severity of neuropathy, diarrhea, orthostatic hypotension, and posterior wall or ventricle septal thickness before and after LT. Fifteen patients underwent LT for amyloidosis at our institution between 1990 and 2000 (MET30, n = 5; NMET30, n = 7; hereditary amyloidosis, n = 2; primary amyloidosis, AL type, n = 1). Patients with hereditary and primary amyloidosis were excluded from analysis. One- and 3-year survival rates after LT in MET30 patients were 100%. Before LT, five of five patients had sensorimotor neuropathy; five of five patients had diarrhea, and four of five patients had orthostatic hypotension. After LT, improvement or stabilization of neuropathy was seen in two of five patients; of diarrheal symptoms, in three of five patients; and of orthostatic hypotension, in three of four patients. One- and 3-year survival rates after LT in NMET30 patients were 100% and 85.7%, respectively. Before LT, six of seven patients had sensorimotor neuropathy, six of seven patients had diarrhea, and five of seven patients had orthostatic hypotension. After LT in this group, improvement or stabilization of neuropathy was seen in two of six patients; of diarrhea, in six of six patients; and of orthostatic hypotension, in five of five patients. Before LT, posterior wall and/or ventricle septal thickness was increased in two of five MET patients and seven of seven NMET patients. Five of seven NMET30 patients (71.4%) who received a combined liver and heart transplant had stabilization, and two patients in the NMET group and one patient in the MET group had progression of heart disease. Outcomes for LT for patients with FAP with MET or NMET mutations were similar. Earlier LT for patients with FAP with MET30 or NMET30 mutation would improve outcomes after LT.

Adult↗
PubMed2005

Studies on nitrosyl hemes in Ni(II)-Fe(II) hybrid hemoglobins.

Subunit heterogeneity within a particular subunit in hemoglobin A have been explored with electron paramagnetic resonance spectroscopy using the nitrosyl hemes in Ni-Fe hybrid Hb under various solution conditions. Our previous studies on the crystal structure of NiHb demonstrated the presence of subunit heterogeneity within alpha-subunit. To further cross check this hypothesis, we made a hybrid Hb in which either the alpha- or beta-subunit contains iron, which alone can bind to NO. By this way dynamic exchange between penta- and hexa-coordinated forms within a subunit was confirmed. Upon the addition of inositol hexa phosphate (IHP) to these hybrids, R to T state transition is observed for [alpha(2)(Fe-NO)beta(2)(Ni)] but such a direct transformation is less marked in [alpha(2)(Ni)beta(2)(Fe-NO)]. Hence the bond between N(epsilon) and Fe is fundamental to the structure-function relation in Hb, as the motion of this nitrogen triggers the vast transformation, which occurs in the whole molecule on attachment of NO.

Electron Spin Resonance Spectroscopy↗
PubMed2005

Purification and in vitro characterization of the maltose-binding protein of the plant pathogen Xanthomonas citri.

The uptake of maltose and maltodextrins in gram-negative bacteria is mediated by an ATP-dependent transport complex composed of a periplasmic maltose-binding protein (MBP) and membrane-associated proteins responsible for the formation of a membrane pore and generation of energy to drive the translocation process. In this work, we report the purification and in vitro functional analysis of MBP, encoded by the malE gene, of the plant pathogen Xanthomonas citri, responsible for the canker disease affecting citrus plants throughout the world. The X. citri MBP is composed of 456 amino acids, displaying a low amino acid identity (16% throughout the sequence) compared to the Escherichia coli K12 ortholog. The X. citri malE gene was cloned into a pET28a vector, and the encoded protein was expressed and purified by affinity chromatography as a His-tag N-terminal fusion peptide produced by the E. coli BL21 strain. Enhanced levels of soluble protein were achieved with static cultures kept overnight at 23 degrees C. Ability to bind immobilized amylose, the emission of intrinsic fluorescence and circular dichroism spectra indicated that the purified recombinant protein preserved both conformation and biological activity of the native protein. The availability of the recombinant MBP will contribute to the functional and structural analysis of the maltose and maltodextrin uptake system of the plant pathogen X. citri.

Amino Acid Sequence↗
PubMed2006

The molybdate-binding protein (ModA) of the plant pathogen Xanthomonas axonopodis pv. citri.

The modABC operon of phytopathogen Xanthomonas axonopodis pv. citri (X. citri) encodes a putative ABC transporter involved in the uptake of the molybdate and tungstate anions. Sequence analyses showed high similarity values of ModA orthologs found in X. campestris pv. campestris (X. campestris) and Escherichia coli. The X. citri modA gene was cloned in pET28a and the recombinant protein, expressed in the E. coli BL21 (DE3) strain, purified by immobilized metal affinity chromatography. The purified protein remained soluble and specifically bound molybdate and tungstate with K(d) 0.29+/-0.12 microM and 0.58+/-0.14 microM, respectively. Additionally binding of molybdate drastically enhanced the thermal stability of the recombinant ModA as compared to the apoprotein. This is the first characterization of a ModA ortholog expressed by a phytopathogen and represents an important tool for functional, biochemical and structural analyses of molybdate transport in Xanthomonas species.

ATP-Binding Cassette Transporters↗
PubMed2005

Kinin and opioid receptors in the paratrigeminal nucleus modulate the somatosensory reflex to rat sciatic nerve stimulation.

The influence of kinin and opioid receptor blockade in the paratrigeminal nucleus (Pa5) on the somatosensory reflex (SSR) to sciatic nerve stimulation (SNS) was assessed in anaesthetized-paralyzed rats. SNS (square 1 ms pulses at 0.6 mA and 20 Hz for 10s) increased mean arterial pressure from 87+/-3 to 106+/-3 mmHg. Pressor responses to SNS were reduced 40-60% by HOE-140 and LF 16-0687 (B2 receptor antagonists; 20 and 100 pmol respectively), CTOP or nor-binaltorphimine (mu and kappa opioid receptor antagonists, respectively; 1 microg) but potentiated by naltrindole (delta opioid receptor antagonist) receptor antagonist microinjections into the contralateral (but not ipsilateral) Pa5. The SSR to sciatic nerve stimulation was not changed by B1 kinin receptor or NK1, NK2 and NK3 tachykinin receptor antagonists administered to the Pa5. Capsaicin pretreatment (40 mg/kg/day, 3 days) abolished the effects of the opioid receptor antagonists, but did not change the effect of kinin B2 receptor blockade on the SSR. Thus, the activity of B2 and opioid receptor-operated mechanisms in the Pa5 contribute to the SSR in the rat, suggesting a role for these endogenous peptides in the cardiovascular responses to SNS.

Animals↗
PubMed2006

Antiproliferative activity and induction of apoptosis in human colon cancer cells treated in vitro with constituents of a product derived from Pistacia lentiscus L. var. chia.

In this report, we demonstrate that a 50% ethanol extract of the plant-derived product, Chios mastic gum (CMG), contains compounds which inhibit proliferation and induce death of HCT116 human colon cancer cells in vitro. CMG-treatment induces cell arrest at G(1), detachment of the cells from the substrate, activation of pro-caspases-8, -9 and -3, and causes several morphological changes typical of apoptosis in cell organelles. These events, furthermore, are time- and dose-dependent, but p53- and p21-independent. Apoptosis induction by CMG is not inhibited in HCT116 cell clones expressing high levels of the anti-apoptotic protein, Bcl-2, or dominant-negative FADD, thereby indicating that CMG induces cell death via a yet-to-be identified pathway, unrelated to the death receptor- and mitochondrion-dependent pathways. The findings presented here suggest that CMG (a) induces an anoikis form of cell death in HCT116 colon cancer cells that includes events associated with caspase-dependent pathways; and (b) might be developed into a chemotherapeutic agent for the treatment of human colon and other cancers.

Antineoplastic Agents, Phytogenic↗
PubMed2006

14-3-3 proteins as potential oncogenes.

14-3-3 proteins are a family of highly conserved cellular proteins that play key roles in the regulation of central physiological pathways. More than 200 14-3-3 target proteins have been identified, including proteins involved in mitogenic and cell survival signaling, cell cycle control and apoptotic cell death. Importantly, the involvement of 14-3-3 proteins in the regulation of various oncogenes and tumor suppressor genes points to a potential role in human cancer. The present review summarizes current findings implicating a 14-3-3 role in cancer while discussing potential mechanisms and points of action of 14-3-3 during cancer development and progression.

14-3-3 Proteins↗
PubMed2004

The effect of fluoride on the scavenging of organophosphates by human butyrylcholinesterase in buffer solutions and human plasma.

Fluoride ion is a reversible inhibitor of human butyrylcholinesterase (HuBChE) that is a viable drug candidate against organophosphates (OPs) toxicity. Since large numbers of communities in many countries are occasionally exposed to relatively high amount of fluoride, its effect on the kinetics of inhibition of HuBChE by OPs was investigated. In saline phosphate, pH 7.4, fluoride in the lower millimolar range significantly slowed the inhibition of HuBChE by paraoxon, DFP, echothiophate, soman, sarin, and VX. The kinetics of the inhibition was found consistent with the formation of a reversible fluoride-HuBChE complex that is at least 25-fold less active towards phosphorylation or phosphonylation than the free enzyme. Heat inactivation experiments indicate that the binding of fluoride to HuBChE probably involves enhanced cross-domain interaction via hydrogen bonds formation that may decrease enzyme activity. In spite of distinct structural differences among the OP used, the dissociation constants of the fluoride-HuBChE reversible complex varied over a narrow range (KF, 0.31-0.70 mM); however, KF in human plasma increased to 2.75-3.40 mM. 19F-NMR spectroscopy revealed that fluoride ion is complexed to plasma components, an observation that explains in part the apparent increase in KF. Results suggest that an estimate of the relative decrease in the rate of OPs sequestration in presence of fluoride can be obtained from the fraction of the free HuBChE (1 + [F]/K(F))(-1). Considering KF values in human plasma, it is concluded that the scavenging efficacy of OPs by HuBChE is not compromised by the normal concentration range of circulating fluoride ions.

Buffers↗
PubMed2004

Intrapreputial infection of young bulls with bovine herpesvirus type 1.2 (BHV-1.2): acute balanoposthitis, latent infection and detection of viral DNA in regional neural and non-neural tissues 50 days after experimental reactivation.

Venereal infection of bulls with bovine herpesvirus type 1.2 (BHV-1.2) may result in acute balanoposthitis followed by the establishment of latent infection, presumably in dorsal root nerve ganglia. We herein report the characterization of the acute and latent infection of young bulls with a Brazilian BHV-1.2 isolate and the investigation of neural and non-neural sites in which viral DNA persists during latent infection, i.e. 110 days after inoculation and 50 days after experimental reactivation. Intrapreputial inoculation of BHV-1.2 isolate SV-56/90 (10(6.5)pfu per animal) resulted in severe balanoposthitis, characterized by redness of the penis and preputial mucosa, coalescent vesicles and fibrinous exsudate in all four infected bulls. Virus shedding was detected in preputial secretions and semen up to days 14 and 13 pi, respectively. Dexamethasone administration at day 60 pi led to reactivation of the infection in all animals, resulting in virus shedding in preputial secretions and/or in semen. At day 50 post-reactivation (pr), the animals were euthanized and regional tissues were collected for PCR and virus isolation. Viral DNA was consistently detected in the dorsal root ganglia of nerves genito-femoral (4/4) and obturator (4/4); frequently in the pudendal (3/4), sciatic (3/4) and rectal caudal nerve ganglia (2/3). In addition, viral DNA was detected in the pelvic sympathetic plexus of one bull and in regional lymph nodes (deep inguinal (2/4); sacral (1/4); medial iliac (1/4)) of two bulls. No infectious virus could be recovered from homogenates of DNA positive tissues, indicating the absence of actively replicating virus. These results demonstrate that BHV-1.2 DNA may persist in several sacral nerve ganglia and in regional lymph nodes as well during latent infection, i.e. 50 days after experimental reactivation. These findings may help in understanding the pathogenesis of acute and latent genital infection by BHV-1.2.

Animals↗
PubMed2004

Molecular comparison of echovirus 11 strains circulating in Europe during an epidemic of multisystem hemorrhagic disease of infants indicates that evolution generally occurs by recombination.

We compared echovirus 11 (E11) strains implicated in a severe epidemic in Hungary in 1989 with the prototype E11 strain Gregory and with other E11 strains, most of which were isolated over the same period in Europe (Finland, The Netherlands, Romania, Russia) from sporadic cases or from environmental water. Partial sequencing indicated that the Hungarian strains were closely related to each other and to most European strains. They were particularly closely related to one Romanian strain associated with a sporadic case of hemiparesis and several Finnish strains isolated from environmental water. Sequencing of the complete genomes of one Hungarian strain, the Romanian strain, and one Finnish strain revealed differences of only a few nucleotides in the 5' half of the genome, including the 5' nontranslated region (5'-NTR) and the capsid coding region. However, significant differences were observed in the nucleotide sequences of the 3' half of the genome (nonstructural viral protein region and 3'-NTR), indicating that these strains evolved recently and independently by genetic recombination with other unknown E11 or enterovirus strains.

Amino Acid Sequence↗
PubMed2000

Treatment of low back pain exacerbations with willow bark extract: a randomized double-blind study.

PURPOSE: Herbal medicines are widely used for the treatment of pain, although there is not much information on their effectiveness. This study was designed to evaluate the effectiveness of willow (Salix) bark extract, which is widely used in Europe, for the treatment of low back pain. SUBJECTS AND METHODS: We enrolled 210 patients with an exacerbation of chronic low back pain who reported current pain of 5 or more (out of 10) on a visual analog scale. They were randomly assigned to receive an oral willow bark extract with either 120 mg (low dose) or 240 mg (high dose) of salicin, or placebo, with tramadol as the sole rescue medication, in a 4-week blinded trial. The principal outcome measure was the proportion of patients who were pain-free without tramadol for at least 5 days during the final week of the study. RESULTS: The treatment and placebo groups were similar at baseline in 114 of 120 clinical features. A total of 191 patients completed the study. The numbers of pain-free patients in the last week of treatment were 27 (39%) of 65 in the group receiving high-dose extract, 15 (21%) of 67 in the group receiving low-dose extract, and 4 (6%) of 59 in the placebo group (P <0.001). The response in the high-dose group was evident after only 1 week of treatment. Significantly more patients in the placebo group required tramadol (P <0.001) during each week of the study. One patient suffered a severe allergic reaction, perhaps to the extract. CONCLUSION: Willow bark extract may be a useful and safe treatment for low back pain.

Administration, Oral↗
PubMedDate not supplied

[Prevalence and evolution of sleep complaints recorded upon medical check-ups in healthcare centers in Bordeaux and Cenon, France, between 1988 and 1998].

Primary healthcare checkups are regularly performed by French healthcare centers. We report analysis of sleep disorders complaint registered from 1988 to 1998 in Bordeaux-Cauderan and Cenon CPAM welfare centers. The prevalence of sleep disorders is estimated from a total of 205 347 checkups. The population is segmented by age (18-24: 19 332, 25-34:46 694, 35-44:51 072, 45-54:46 886, 55-64:32 658, 65 +:7 705), gender (male: 101 801; female: 103 546) and population category (general: 147 188, underprivileged: 22 785, prioritized: 35 374). Datas shows a relationship between sex and age. Surprisingly we found a relation between Buying Power for Net Wages and Prevalence of Sleep Complaint. There is a significant correlation (R(2)=0,718, p<0,0079). These data are in relationship with M. Ohayon findings relatively to low income and sleep complaint.

Adult↗
PubMed1988

Amyloidosis presenting as a penile mass.

We report a unique case of amyloidosis presenting as a localized soft tissue mass in the shaft of the penis unassociated with systemic amyloidosis, trauma, penile ulcers, syphilis or other venereal diseases. The patient presented with a penile mass and intermittent hematuria. Biopsy revealed homogeneous deposits of amorphous eosinophilic material, and histochemistry and electron microscopy demonstrated the classical features of amyloid.

Adult↗