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At least 1,261 records · Page 70Linked to original sources
PubMed1995

Age-related impairment in striatal muscarinic cholinergic signal transduction is associated with reduced membrane bilayer width measured by small angle X-ray diffraction.

In order to determine whether age-related changes in neuronal membrane structure contribute to previously reported changes in muscarinic cholinergic signal transduction, striata from 3, 13 and 23 month old F344 male rats were examined for both carbachol-stimulated low Km GTPase activity and membrane one-dimensional electron density profile using small angle X-ray diffraction. Increasing age was associated with both a reduction in stimulated GTPase activity and a decrease in membrane bilayer width. These findings suggest the possibility that fundamental membrane structural changes may contribute to alterations in signal transduction seen with aging.

Aging↗
PubMed1994

Overview of radioimmunotherapy in advanced breast cancer using I-131 chimeric L6.

131I chimeric L6 (ChL6) monoclonal antibody (MoAb) therapy has been performed in 12 patients with advanced, metastatic breast cancer. The protocol was designed to determine the maximum tolerated dose (MTD) of radioimmunotherapy that could be administered at 4 intervals. Ten patients received 20-70 mCi/m2 of 131I ChL6. Two of the patients received granulocyte colony stimulating factor (GCSF) on days 10-20 post therapy. The MTD for two doses was 60 mCi/m2 and thrombocytopenia was the dose limiting toxicity in the absence of marrow reconstitution with stem cells. Two patients received 150 mCi/m2 with autologous peripheral blood stem cell support 7 and 9 days post treatment. The MTD has not been reached for 131I-ChL6 with autologous stem cell support. In the 12 patients treated with 131I ChL6, six patients (50%) had measurable tumor regressions greater than 30% of the sum of the largest two dimensional products for measurable tumors. Four of these 6 patients had a partial response (PR), i.e., > or = 50% reduction in tumor size. These therapeutic responses associated with modest clinical toxicity in heavily pretreated patients suggest that clinically relevant radioimmunotherapeutic approaches can be devised for metastatic breast cancer.

Animals↗
PubMed1989

Interprotein disulfide bonding between F and G glycoproteins of human respiratory syncytial virus.

The envelope glycoprotein G, of human respiratory virus was purified by immunoaffinity chromatography using a monoclonal antibody reacting with G glycoprotein. The purified material was analyzed for its protein patterns and by western blot for its reactivity with specific monoclonal antibodies. In addition to the G specific proteins at 90 and 55 kilodalton (kDa) range, high molecular weight species were coeluted with G protein. Three high molecular weight species were noticed: one (140 kDa) reacting with fusion protein (F) monoclonal antibody and two other species (230 and 195 kDa) reacting with both fusion protein and G protein monoclonal antibodies. The protein reacting only with F monoclonal antibody consists of fusion protein dimer. Western blot and two dimensional gel electrophoretic analysis revealed that each of the other two complexes is composed of two moles of F protein and one mole of G protein. These two complexes differ in their molecular sizes depending on whether G is in the form of 90 or 55 kDa. Upon heat denaturation, fusion protein monomer (70 kDa) is released from the complex, leaving the two complexes, consisting of one mole of F protein and one mole of G protein (160 and 125 kDa species respectively). Disulfide-reducing agents are required to break the monomers of F and G complexes. These results provide a direct evidence for the presence of envelope glycoprotein complexes linked by interprotein disulfide bonding. This may have implications on the structural and functional properties of envelope glycoproteins.

Antibodies, Monoclonal↗
PubMed1993

Efficacy of ganciclovir in combination with zidovudine against cytomegalovirus in vitro and in vivo.

In cultured MRC-5 cells, ganciclovir (GCV) alone had good activity against both the established AD169 strain (IC50 8 and 9 microM) and a clinical isolate (IC50 14 microM) of human cytomegalovirus (CMV), while 3'-azido-3'-deoxythymidine (AZT) was relatively inactive [IC50 508 and > 800 (AD169 strain); > 800 microM (clinical isolate)]. When reductions in plaques were compared against reductions in the cellular metabolism of MTT at all GCV and AZT combination concentrations using an improved 3-dimensional linear regression analysis, AZT had an additive effect on the antiviral activity of GCV against the AD169 strain and potentiated the antiviral activity of GCV against the clinical isolate. Calculations showed that, in the presence of 50 microM AZT, the anti-CMV activity of GCV was unchanged for the AD169 strain, whereas the activity of GCV was increased approximately 5-10-fold for the clinical isolate. An increase in GCV efficacy for the AD169 strain first became apparent at 100 microM AZT with an approximately 3-fold increase in activity. In Swiss-Webster mice, the anti-CMV activity of GCV against murine CMV was unaffected when administered in combination with AZT. GCV given alone subcutaneously had an ED50 of 6 mg/kg which was unaffected by daily intraperitoneal doses of 320 mg/kg AZT. These results suggest that AZT will not adversely affect the efficacy of GCV against CMV in HIV-positive, non-neutropenic patients.

Animals↗
PubMed1991

The tammar wallaby major plasma serpin: partial characterization including the sequence of the reactive site region.

1. The putative equivalent of the human major plasma serpin (alpha 1-proteinase inhibitor or alpha 1-antitrypsin) in the tammar wallaby (Macropus eugenii) has been further characterized by structural (peptide and immunopeptide mapping and sequence studies) and functional analyses revealing close homology of the wallaby proteins to human alpha 1-proteinase inhibitor. 2. A sixth allele, Pi J, was detected and its products characterized in terms of pI, Mr, inhibitory spectra and terminal sialic acid content. 3. A recently-developed electrophoretic in situ oxidation/binding method was adapted to provide protein suitable for sequence analysis of the N-terminus and reactive site region including assignment of the P1 and P'1 residues. 4. All sequence analyses were performed on proteins or peptides (approximately Mr 3500) blotted onto polybrene treated GF/C or polyvinylidene difluoride membrane respectively. 5. The P5 to P'4 residues of the reactive centre are identical with those of the human inhibitor thereby allowing the wallaby inhibitor also to be classified as a METserpin. 6. The P1 methionine is presumably responsible for the oxidation sensitivity observed in the electrophoretic in situ functional assay for the wallaby inhibitor. 7. The plasma concentration of the wallaby inhibitor is similar to that reported for human alpha 1-proteinase inhibitor.

Alleles↗
PubMed2005

Redox proteomics analysis of oxidatively modified proteins in G93A-SOD1 transgenic mice--a model of familial amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron degenerative disease characterized by the loss of neuronal function in the motor cortex, brain stem, and spinal cord. Familial ALS cases, accounting for 10-15% of all ALS disease, are caused by a gain-of-function mutation in Cu,Zn-superoxide dismutase (SOD1). Two hypotheses have been proposed to explain the toxic gain of function of mutant SOD (mSOD). One is that mSOD can directly promote reactive oxygen species and reactive nitrogen species generation, whereas the other hypothesis suggests that mSODs are prone to aggregation due to instability or association with other proteins. However, the hypotheses of oxidative stress and protein aggregation are not mutually exclusive. G93A-SOD1 transgenic mice show significantly increased protein carbonyl levels in their spinal cord from 2 to 4 months and eventually develop ALS-like motor neuron disease and die within 5-6 months. Here, we used a parallel proteomics approach to investigate the effect of the G93A-SOD1 mutation on protein oxidation in the spinal cord of G93A-SOD1 transgenic mice. Four proteins in the spinal cord of G93A-SOD1 transgenic mice have higher specific carbonyl levels compared to those of non-transgenic mice. These proteins are SOD1, translationally controlled tumor protein (TCTP), ubiquitin carboxyl-terminal hydrolase-L1 (UCH-L1), and, possibly, alphaB-crystallin. Because oxidative modification can lead to structural alteration and activity decline, our current study suggests that oxidative modification of UCH-L1, TCTP, SOD1, and possibly alphaB-crystallin may play an important role in the neurodegeneration of ALS.

Amyotrophic Lateral Sclerosis↗
PubMed2005

The three-dimensional structure of trichocyte (hard alpha-) keratin intermediate filaments: features of the molecular packing deduced from the sites of induced crosslinks.

The spatial distribution of the crosslinks that can be induced between lysine residues in trichocyte (alpha-) keratin intermediate filaments (IF) using disulfosuccinimidyl tartrate has been analyzed in detail and the results used to provide information about the three-dimensional (3-D) structure. The pattern of inter-molecular interactions derived from earlier studies is essentially two-dimensional in that it involves projection on to a cylinder followed by unwrapping to give a sheet. Crosslinks are observed between molecular strands four apart and it is shown that this can only occur if the paths of the molecular strands through the IF are systematically distorted. These crosslinks are clustered axially at intervals of around 15 nm, a value closely related to the pitch length of the constituent coiled-coil molecules in the rod domains. The number of crosslinks between adjacent molecular strands shows a striking difference depending on lateral direction and provides support for the concept of a head-to-tail stacking of tetramers defined by the A(CN) mode of packing to form protofilament substructures in the fully formed IF. Each protofilament would consist of a pair of oppositely directed molecular strands stabilized by A(11) and A(22) interactions identified in earlier work. A detailed model for the IF in the reduced state comprising a ring of eight protofilaments is suggested. When combined with earlier studies of crosslink formation in the oxidized state, the present findings lead to the conclusion that there is a major reorganization of the molecular packing within the protofilaments during keratinization in vivo. Taken in conjunction with existing X-ray data on the fully keratinized structures, the new evidence for a protofilament substructure also enables a detailed 3-D model for the mature IF to be suggested.

Animals↗
PubMed2006

Redox proteomics in the mussel, Mytilus edulis.

Pollutants (e.g. PAHs, metals) cause oxidative stress (OS) by forming reactive oxygen species. Redox proteomics provides a means for identifying protein-specific OS effects in Mytilus edulis. Groups of mussels were sampled from a clean site in Cork Harbour, Ireland and exposed to 1 mM H2O2 in holding tanks. Protein extracts of gill and digestive gland were separated by two dimensional electrophoresis and similar protein expression profiles were found. Effects of OS on disulphide bridge patterns were investigated in diagonal gels by separating proteins in non-reducing conditions followed by a second reducing dimension. Immunoprecipitation selected carbonylated and glutathionylated proteins. These methodologies can contribute to redox proteomic studies of pollutant responses in marine organisms.

Actins↗
PubMed2003

Human beta-crystallins modified by backbone cleavage, deamidation and oxidation are prone to associate.

Information about beta-crystallins and their post-translational modifications has been scarce because of difficulties in isolating the individual beta-crystallins. These difficulties arise because the beta-crystallin sequences are highly homologous and because beta-crystallins undergo many age-related modifications that lead to a variety of molecular masses and a range of acidities for each crystallin. In this study, human beta-crystallins were isolated using several steps of chromatography both before and after two-dimensional gel electrophoresis. Many previously unidentified in vivo modifications, including deamidations among all beta-crystallins except betaB3, truncation of betaA3, betaB1 and betaA4, and oxidation of some methionines and tryptophans were located among the isolated beta-crystallins. Many modifications occurred before age 20 with modest increases in modification for beta-crystallins from lenses 20-87 years old. The tendency of the modified beta-crystallins to form non-covalent complexes was evident from their chromatographic behaviour. The presence in these complexes of betaB2-crystallin, the least modified and most soluble of the beta-crystallins, points to a possible role for betaB2 in solubilizing the more heavily modified beta-crystallins. The greater solubility of beta-crystallins compared with alpha- and gamma-crystallins in aging lenses may be due to beta-crystallin modifications and their non-covalent associations.

Adult↗
PubMed1998

A three-dimensional analysis of a fibre-reinforced aortic valve prosthesis.

Failure of synthetic heart valves is usually caused by tearing and calcification of the leaflets. It is postulated that leaflet fibre-reinforcement leads to a decrease of tears and perforations as a result of reduced stresses in the weaker parts of the leaflets. A three-dimensional finite element model of a reinforced three-leaflet valve prosthesis was developed to analyse the stress reduction. Different fibre reinforcements were investigated and the model responses were analysed for stresses that are expected to contribute to failure of fibre-reinforced valve prostheses. Results of these simulations show that, in peak stress areas of reinforced models, up to 60% of the maximum principal stresses is taken over by fibres and that, in some cases of reinforcement, a more homogeneous stress distribution is obtained.

Alkenes↗
PubMed2001

Design parameters for an electrochemical cell with porous electrode to treat metal-ion solution.

An electrochemical reactor was designed and operated to treat the solution containing copper ions. Design parameters for the electrochemical reactor using the porous cathode and RuO2/IrO2/Ti anode were investigated. The porous cathode was prepared by the electroless nickel deposition on polyurethane. The apparent current, the gap between cathode and anode, and hydraulic retention time (HRT) were selected as design parameters. The copper removal rate increased with an increase in apparent current. It was not affected by the gap between the cathode and the anode. A reduction in hydraulic retention time stimulated the mass transfer toward the electrode and increased the cathodic current efficiency. Dimensional analysis was conducted to obtain the design equation for scale-up of the electrochemical reactor. The dependence of Sh on Re, Sc, and characteristic lengths, DC/A/L and DW/C/L, was described in the form of a power series. The coefficients were obtained from experimental data.

Cations↗
PubMed2003

Redox control of changes in protein sulfhydryl levels during human sperm capacitation.

Capacitation, the series of transformations that spermatozoa undergo to become fertile, is regulated by reactive oxygen species (ROS) and associated with an increase in the sulfhydryl content of Triton-soluble proteins. Our aims were to determine the fate of sulfhydryl groups in Triton-soluble proteins from capacitating human spermatozoa using two-dimensional (2D) gel electrophoresis, to evaluate the role of ROS in the changes observed, and to correlate the time course of the changes with that of the sperm generation of O(2)(*)(-). Triton-soluble proteins of control and capacitating human spermatozoa were labeled with 3-(N-maleimidylpropionyl) biocytin, separated by 2D gel electrophoresis, and probed with horseradish peroxidase-conjugated streptavidin. The sulfhydryl content of 10 out of the 14 proteins studied (pI: 4-7) was modified by the induction of capacitation, and the increases (by 200-400%, five proteins) and decreases (by 45-95%, five proteins) were prevented by superoxide dismutase and/or catalase. The alterations in protein sulfhydryl content occurred within 5-15 min but were reversed within 30-120 min. Three capacitation inducers triggered similar modifications. Therefore, human sperm capacitation is associated with rapid and reversible changes in protein sulfhydryl groups that appear to be redox regulated. The number of proteins affected, the types, and the kinetics of changes emphasize the complexity of sperm capacitation.

Catalase↗
PubMed1997

A modified form of low-density lipoprotein with increased electronegative charge is present in rheumatoid arthritis synovial fluid.

Reactive oxygen species (ROS) are pro-inflammatory factors in the pathogenesis of rheumatoid arthritis. During inflammation, the amount of low-density lipoprotein (LDL) in the inflamed joint is increased. LDL is known to be susceptible to oxidation by ROS. Oxidized LDL may serve as a mediator for joint damage, further exacerbating the inflammatory process. LDL isolated from synovial fluid and plasma from individual patients (paired samples) with rheumatoid arthritis or osteoarthritis was characterized by crossed immunoelectrophoresis. On analysis by this technique, synovial fluid LDL from most patients with rheumatoid arthritis contained two peaks: one corresponding to normal plasma native LDL, and the other having an increased electrophoretic mobility associated with oxidized LDL. Paired plasma LDL samples contained native LDL alone, as did paired synovial fluid and plasma LDL from patients with osteoarthritis. Thus, in addition to native LDL, a second form of LDL was shown to be present in rheumatoid synovial fluid, which had properties consistent with those of oxidized LDL.

Aged↗
PubMed2005

Correlation coefficient mapping in fluorescence spectroscopy: tissue classification for cancer detection.

Correlation coefficient mapping has been applied to intrinsic fluorescence spectra of colonic tissue for the purpose of cancer diagnosis. Fluorescence emission spectra were collected of 57 colonic tissue sites in a range of 4 physiological conditions: normal (29), hyperplastic (2), adenomatous (5), and cancerous tissues (21). The sample-sample correlation was used to examine the ability of correlation coefficient mapping to determine tissue disease state. The correlation coefficient map indicates two main categories of samples. These categories were found to relate to disease states of the tissue. Sensitivity, selectivity, predictive value positive, and predictive value negative for differentiation between normal tissue and all other categories were all above 92%. This was found to be similar to, or higher than, tissue classification using existing methods of data reduction. Wavelength-wavelength correlation among the samples highlights areas of importance for tissue classification. The two-dimensional correlation map reveals absorption by NADH and hemoglobin in the samples as negative correlation, an effect not obvious from the one-dimensional fluorescence spectra alone. The integrity of tissue was examined in a time series of spectra of a single tissue sample taken after tissue resection. The wavelength-wavelength correlation coefficient map shows the areas of significance for each fluorophore and their relation to each other. NADH displays negative correlation to collagen and FAD, from the absorption of emission or fluorescence resonance energy transfer. The wavelength-wavelength correlation map for the decay set also clearly shows that there are only three fluorophores of importance in the samples, by the well-defined pattern of the map. The sample-sample correlation coefficient map reveals the changes over time and their impact on tissue classification. Correlation coefficient mapping proves to be an effective method for sample classification and cancer detection.

Adenomatous Polyposis Coli↗
PubMed2004

Source apportionment of visibility impairment using a three-dimensional source-oriented air quality model.

A three-dimensional source-oriented Eulerian air quality model is developed that can predict source contributions to the visibility reduction. Particulate matter and precursor gases from 14 different sources (crustal material, paved road dust, diesel engines, meat cooking, noncatalyst-equipped gasoline engines, catalyst-equipped gasoline engines, high-sulfur fuel, sea salt, refrigerant losses, residential production, animals, soil and fertilizer application, other anthropogenic sources, and background sources) are tracked though a mathematical simulation of emission, chemical reaction, gas-to-particle conversion, transport, and deposition. A visibility model based on Mie theory is modified to use the calculated source contributions to airborne particulate matter size and composition as well as gas-phase pollutant concentrations to quantify total source contributions to visibility impairment. The combined air quality-visibility model is applied to predict source contributions to visibility reduction in southern California for a typical air pollution episode (September 23-25, 1996). The model successfully predicts a severe visibility reduction in the eastern portion of the South Coast Air Basin where the average daytime visibility is measured to be less than 10 km. In the relatively clean coastal portion of the domain, the model successfully predicts that the average daytime visibility is greater than 65 km. Transportation-related sources directly account for approximately 50% of the visibility reduction (diesel engines approximately 15-20%, catalyst-equipped gasoline engines approximately 10-20%, noncatalyst-equipped gasoline engines approximately 3-5%, crustal and paved road dust approximately 5%) in the region with the most severe visibility impairment. Ammonia emissions from animal sources account for approximately 10-15% of the visibility reduction.

Air Movements↗
PubMed1999

N-glycan structures of murine hippocampus serine protease, neuropsin, produced in Trichoplusia ni cells.

N-glycans of neuropsin (serine protease in the murine hippocampus) expressed in Trichoplusia ni cells were released from the glycopeptides by digestion with glycoamidase A (from sweet almond), and the reducing ends of the oligosaccharides were reductively aminated with 2-aminopyridine. The derivatized N-glycans were separated and structurally identified by a two dimensional high-performance liquid chromatography (HPLC) mapping technique on two kinds of HPLC columns. Fourteen different major N-glycan structures were identified, of which 6 were high-mannose type (9.1%), and the remaining 8 were paucimannosidic type. The presence of insect specific N-glycan structures containing both alpha1,3- and alpha1,6- di-fucosylated innermost N-acetylglucosamine residue (23.3%), as below, was also confirmed by 600 MHz 1H-NMR spectroscopy.

Animals↗
PubMed1991

A three-disulphide derivative of hen lysozyme. Structure, dynamics and stability.

A three-disulphide derivative of hen egg-white lysozyme was made by selective reduction and carboxymethylation of one of the four original disulphide bridges. N-Terminal sequencing and two-dimensional 1H-n.m.r. spectroscopy revealed that the disulphide bridge linking cysteine residues 6 and 127 had been modified and that the three remaining disulphide bonds were native-like in nature. Analysis of COSY and NOESY spectra indicated that the three-disulphide lysozyme (CM6.127-lysozyme retains the same secondary and tertiary structure as its four-disulphide counterpart; its stability to pH and temperature is, however, dramatically decreased. N.m.r. spectroscopy was used to characterize the thermal folding and unfolding transition of CM6.127-lysozyme. Not only is the transition still a highly co-operative event, but the enthalpy change associated with folding and unfolding resembles that of intact lysozyme when their differences in thermal stability are taken into consideration. The significance of these results in terms of the folding process of lysozyme is discussed. By contrast with authentic lysozyme, CM6.127-lysozyme was found to exist in an unfolded state at pH 2 at room temperature. N.m.r. spectroscopy and c.d. were used to characterize this state. Unlike their homologous relative, alpha-lactalbumin, which exists in a partially folded molten globule state under these conditions, only residual non-native-like structure persists in the acid-unfolded state of CM6.127-lysozyme. These results indicate that the difference in folding behaviour of lysozyme and alpha-lactalbumin cannot be accounted for simply by their differences in thermal stability.

Animals↗