Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Four semi-empirical methods (PM3, AM1, MNDO and MINDO3) have been tested to find the best auxiliary tool for the gas chromatography/Fourier transform IR spectroscopy/mass spectrometry (GC/FTIR/MS) identification of five compounds of interest for Titan's atmospheric chemistry as test compounds: diacetylene, triacetylene, diazomethane, methyl azide, methyl isocyanide. Of the four methods, MINDO3 can be considered as the most appropriate method to facilitate the identification of such and similar compounds, since (1) the simulated IR spectra best match the experimental spectra for four compounds of five studied; and (2) MINDO3 provides the best linearity between the calculated and experimental frequencies (correlation coefficient of 0.995; a scaling factor of 0.84 can be applied to afford better correspondence between the calculated and experimental wavenumbers). None of the semi-empirical methods tested is able to predict (even approximately) infrared band intensities, and therefore a spectral intensity pattern.
Spectrochim Acta A Mol Biomol Spectrosc 2001 Mar 01
PMID:PM3, AM1, MNDO and MINDO3 semi-empirical IR spectra simulations for compounds of interest for Titan's chemistry: diazomethane, methyl azide, methyl isocyanide, diacetylene and triacetylene. 1130 May 62

Metal toxicity from sources such as orthopaedic implants was investigated in terms of immune system hyper-reactivity to metal implant alloy degradation products. Lymphocyte response to serum protein complexed with metal from implant alloy degradation was investigated in this in vitro study using primary human lymphocytes from healthy volunteers (n = 10). Cobalt chromium molybdenum alloy (Co-Cr-Mo, ASTM F-75) and titanium alloy (Ti-6Al-4V, ASTM F-136) beads (70 microm) were incubated in agitated human serum at 37 degrees Celsius to simulate naturally occurring metal implant alloy degradation processes. Particulate free serum samples, which were incubated with metal, were then separated into molecular weight based fractions. The amounts of soluble Cr and Ti within each serum fraction were measured and correlated with lymphocyte proliferation response to the individual serum fractions. Lymphocytes from each subject were cultured with 11 autologous molecular weight based serum fractions either with or without added metal. Two molecular weight ranges of human serum proteins were associated with the binding of Cr and Ti from Co-Cr-Mo and Ti implant alloy degradation (at < 30 and 180-330 kDa). High molecular weight serum proteins (approximately 180 kDa) demonstrated greater lymphocyte reactivity when complexed with metal released from Co-Cr-Mo alloy and Ti alloy than with low (5-30 kDa) and midrange (30-77 kDa) serum proteins. When the amount of lymphocyte stimulation was normalized to both the moles of metal and the moles of protein within each fraction (Metal-Protein Complex Reactivity Index, MPCRI), Cr from Co-Cr-Mo alloy degradation demonstrated approximately 10 fold greater reactivity than Ti in the higher molecular weight serum proteins (approximately 180-250 kDa). This in vitro study demonstrated a lymphocyte proliferative response to both Co-Cr-Mo and Ti alloy metalloprotein degradation products. This response was greatest when the metals were complexed with high molecular weight proteins, and with metal-protein complexes formed from Co-Cr-Mo alloy degradation.
Mol Cell Biochem 2001 Jun
PMID:Orthopaedic implant related metal toxicity in terms of human lymphocyte reactivity to metal-protein complexes produced from cobalt-base and titanium-base implant alloy degradation. 1167 94

There is now considerable evidence for an association between the levels of particulate air pollution [particulate matter <10 microm in aerodynamic diameter (PM(10))] and various adverse health endpoints. The release of proinflammatory mediators from PM(10)-exposed macrophages may be important in stimulating cytokine release from lung epithelial cells, thus amplifying the inflammatory response. A549 cells were treated with conditioned media from monocyte-derived macrophages stimulated with PM(10), titanium dioxide (TiO(2)), or ultrafine TiO(2). We demonstrate that only conditioned media from PM(10)-stimulated macrophages significantly increased nuclear factor-kappaB and activator protein-1 DNA binding, enhanced interleukin-8 (IL-8) mRNA levels as assessed by RT-PCR, and augmented IL-8 protein levels, over untreated controls. Furthermore, PM(10)-conditioned media also caused transactivation of IL-8 as determined by an IL-8-chloramphenicol acetyl transferase reporter. Analysis of these conditioned media revealed marked increases in tumor necrosis factor-alpha (TNF-alpha) and protein levels and enhanced chemotactic activity for neutrophils. Preincubation of conditioned media with TNF-alpha-neutralizing antibodies significantly reduced IL-8 production. These data suggest that PM(10)-activated macrophages may amplify the inflammatory response by enhancing IL-8 release from lung epithelial cells, in part, via elaboration of TNF-alpha.
Am J Physiol Lung Cell Mol Physiol 2002 Feb
PMID:PM(10)-exposed macrophages stimulate a proinflammatory response in lung epithelial cells via TNF-alpha. 1179 28

Interactions between alveolar macrophages (AMs) and epithelial cells may promote inflammatory responses to air pollution particles. Normal rat AMs, the alveolar type II epithelial cell line RLE-6TN (RLE), or cocultures of both cell types were incubated with various particles (0-50 microg/ml) for 24 h, followed by assay of released TNF-alpha and MIP-2. The particles used included titanium dioxide (TiO2), alpha-quartz (SiO2), residual oil fly ash (ROFA), or urban air particles (UAP). For all particles, a dose-dependent increase in TNF-alpha and MIP-2 release was observed in AM+RLE co-cultures but not in RLE or AM monoculture. AM+RLE co-culture also synergistically enhanced basal levels of tumor necrosis factor (TNF)-alpha and macrophage inflammatory protein (MIP)-2. In contrast, when AMs were co-cultured with fibroblasts, basal and particle-induced TNF-alpha and MIP-2 were similar to levels found in AM monoculture. Particle uptake by AMs was similar in mono- or AM+RLE co-culture. Increased basal and particle-induced cytokine release were not observed when the AMs were physically separated from the RLE. This contact-dependent cytokine potentiation could not be blocked with anti-CD18/anti-CD54, arginine-glycine-aspartate (RGD) peptide, or heparin. We conclude that in vitro inflammatory responses to particles are amplified by contact-dependent interactions between AMs and epithelial cells. AM-epithelial co-culture may provide a useful model of in vivo particle effects.
Am J Respir Cell Mol Biol 2002 Apr
PMID:Lung macrophage-epithelial cell interactions amplify particle-mediated cytokine release. 1191 87

Occupational exposure to crystalline silica is associated with the development of pulmonary inflammation and silicosis, yet how silica initiates pulmonary fibrosis and which cell types are involved are unclear. In studies here, we hypothesized that silica particles interact initially with pulmonary epithelial cells and alveolar macrophages (AMs) to cause transcriptional activation of nuclear factor (NF)-kappaB-regulated genes encoding inflammatory cytokines. Exposure of NF-kappaB luciferase reporter mice intratracheally to silica or lipopolysaccharide (LPS), but not the nonfibrogenic particle titanium dioxide (TiO(2)), increased immunoreactivity of luciferase protein in bronchiolar epithelial cells and AMs. Ribonuclease protection assays revealed significant (P < or = 0.05) increases in mRNA levels of inducible nitric oxide synthase, tumor necrosis factor-alpha, macrophage inflammatory protein-2, macrophage chemotactic protein-1 (MCP-1), interferon-gamma, interleukin (IL)-6, and IL-12 in lung homogenates of reporter mice after exposures to silica or LPS. Immunoreactivity of MCP-1 in these animals was localized to AMs and epithelial cells. These data are the first to show activation of NF-kappaB in situ by fibrogenic particles in pulmonary epithelial cells and AMs. Increased expression of NF-kappaB-related inflammatory cytokines by these cell types, which first encounter silica after inhalation, may be critical to the initiation of silica-associated lung diseases, thus providing a rationale for focusing on NF-kappaB in preventive and therapeutic strategies.
Am J Physiol Lung Cell Mol Physiol 2002 May
PMID:Activation of NF-kappaB-dependent gene expression by silica in lungs of luciferase reporter mice. 1194 61

The interaction of H2O2 with TS-1 has been investigated by the ESR technique. A well manufactured TS-1 has been considered, where the presence of extra-structural titanium can be excluded. The two main signals observed are attributed to oxygen radical species co-ordinated on structural titanium sites, and the relevant effect of water presence in the paramagnetic complex is discussed. A comparison is performed with O2-/Ti species in TS-1 obtained by reduction/re-oxidation procedures of Ti(IV). Moreover, some possible structural configurations of the paramagnetic sites are proposed, for two of which ab initio calculation yield g(z)-values quite close to the experimental ones.
Spectrochim Acta A Mol Biomol Spectrosc 2002 Apr
PMID:An ESR study of titanium-silicalite in presence of H2O2. 1199 62

Asbestos causes asbestosis and malignancies by mechanisms that are not fully understood. Alveolar epithelial cell (AEC) injury by iron-derived reactive oxygen species (ROS) is one important mechanism implicated. We previously showed that iron-catalyzed ROS in part mediate asbestos-inducedAEC DNA damage and apoptosis. Mitochondria have a critical role in regulating apoptosis after exposure to agents causing DNA damage but their role in regulating asbestos-induced apoptosis is unknown. To determine whether asbestos causes AEC mitochondrial dysfunction, we exposed A549 cells to amosite asbestos and assessed mitochondrial membrane potential changes (delta(psi)m) using a fluorometric technique involving tetremethylrhodamine ethyl ester (TMRE) and mitotracker green. We show that amosite asbestos, but not an inert particulate, titanium dioxide, reduces delta(psi)m after a 4 h exposure period. Further, the delta(psi)m after 4 h was inversely proportional to the levels of apoptosis noted at 24 h as assessed by nuclear morphology as well as by DNA nucleosome formation. A role for iron-derived ROS was suggested by the finding that phytic acid, an iron chelator, blocked asbestos-induced reductions in A549 cell delta(psi)m and attenuated apoptosis. Finally, overexpression of Bcl-xl, an anti-apoptotic protein that localizes to the mitochondria, prevented asbestos-induced decreases in A549 cell delta(psi)m after 4 h and diminished apoptosis. We conclude that asbestos alters AEC mitochondrial function in part by generating iron-derived ROS, which in turn can result in apoptosis. This suggests that the mitochondrial death pathway is important in regulating pulmonary toxicity from asbestos.
Mol Cell Biochem
PMID:Asbestos-induced alveolar epithelial cell apoptosis: role of mitochondrial dysfunction caused by iron-derived free radicals. 1216 28

The mechanisms underlying asbestos-induced pulmonary toxicity are not fully understood. Alveolar epithelial cell (AEC) apoptosis by iron-derived reactive oxygen species (ROS) is one important mechanism implicated. The two major pathways regulating apoptosis include (i) the mitochondrial death (intrinsic) pathway caused by DNA damage, and (ii) the plasma-membrane death receptor (extrinsic) pathway. However, it is unknown whether asbestos activates either death pathway in AEC. We determined whether asbestos triggers AEC mitochondrial dysfunction by exposing cells (A549 and rat alveolar type II) to amosite asbestos and assessing mitochondrial membrane potential changes (deltapsi(m)) using a fluorometric technique involving tetremethylrhodamine ethyl ester (TMRE) and mitotracker green. Unlike inert particulates (titanium dioxide and glass beads), amosite asbestos caused dose- and time-dependent reductions in deltapsi(m). Asbestos-induced deltapsi(m) was associated with the release of cytochrome c from the mitochondria to the cytoplasm as well as activation of caspase 9, a mitochondrial-activated caspase. In contrast, a lower level of caspase 8, the death receptor-activated caspase, was detected in asbestos-exposed AEC. An iron chelator (phytic acid or deferoxamine) or a hydroxyl radical scavenger (sodium benzoate) each blocked asbestos-induced reductions in deltapsi(m) and caspase 9 activation, suggesting a role for iron-derived ROS. Finally, Bcl-X(L), a mitochondrial antiapoptotic protein that prevents cell death by preserving the outer mitochondrial membrane integrity, blocked asbestos-induced decreases in A549 cell deltapsi(m) and reduced apoptosis as assessed by DNA fragmentation. We conclude that asbestos-induced AEC apoptosis results from mitochondrial dysfunction, in part due to iron-derived ROS, which is followed by the release of cytochrome c and caspase 9 activation. Our findings suggest an important role for the mitochondria-regulated death pathway in the pathogenesis of asbestos-associated pulmonary toxicity.
Am J Respir Cell Mol Biol 2003 Feb
PMID:The mitochondria-regulated death pathway mediates asbestos-induced alveolar epithelial cell apoptosis. 1254 Apr 92

Titan (formerly Trilex) is developing TriGem, a monoclonal antibody directed against I17, for the potential treatment of advanced cancers that express the GD2 ganglioside, including melanoma, small-cell lung cancer, neuroblastoma and sarcoma. Phase II trials of TriGem for use in advanced melanoma were ongoing by June 2002. TriGem also has potential for the treatment of psoriasis, for which phase II trials had begun by 1996.
Curr Opin Mol Ther 2003 Apr
PMID:Technology evaluation: TriGem, Titan. 1277 13

The major advantages of "naked DNA gene therapy" are its simplicity and a low or negligible immune response. Gene delivery by DNA electroporation (EP) involves injection of DNA and the application of a brief electric pulse to enhance cellular permeability. Although EP is an efficient gene transduction technique in rodents, it requires much higher voltages (>500 V) in larger animals, and hence, in practice it would be hazardous for human patients, as it would cause serious tissue damage. To overcome the obstacles associated with EP-mediated gene delivery in vivo, we developed a new method of gene transduction that uses laser energy. The femtosecond infrared titanium sapphire laser beam was developed specifically for enhancing in vivo gene delivery without risks of tissue damage. System optimization revealed that injection of 10 micro g naked DNA into the tibial muscle of mice followed by application of the laser beam for 5 s, focused to 2 mm depth upon an area of 95 x 95 micro m(2), resulted in the highest intensity and duration of gene expression with no histological or biochemical evidence of muscle damage. We assessed the potential clinical application of LBGT technology by using it to transfer the murine erythropoietin (mEpo) gene into mice. LBGT-mediated mEpo gene delivery resulted in elevated (>22%) hematocrit levels that were sustained for 8 weeks. Gene expression following LBGT was detected for >100 days. Hence, LBGT is a simple, safe, effective, and reproducible method for therapeutic gene delivery with significant clinical potential.
Mol Ther 2003 Aug
PMID:Femtosecond infrared laser-an efficient and safe in vivo gene delivery system for prolonged expression. 1290 57


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