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At least 1,009 records · Page 56Linked to original sources
PubMed2005

Morin sulphates/glucuronides enhance macrophage function in microgravity culture system.

BACKGROUND: The immune system changes significantly in astronauts during and after space flight. Although the mechanism has not been defined, it is reasonable to begin developing effective countermeasures to the physiological consequences of spaceflight, especially immunosuppression. Many studies have been published about the effect of flavonoids on immune modulation. Thus, the aim of this study was to develop whether flavonoids could be the effective countermeasures to the immunosuppression caused by microgravity. MATERIALS AND METHODS: We used a rotating wall vessel 3D (three-dimensional) culture system which recreates some of the culture conditions that occur during microgravity to study the effects of microgravity on the function of macrophages and assess the modulating effects of flavonoids on microgravity-induced macrophage dysfunction. RESULTS: We demonstrated 65% and 80% reduction in mitogen-induced nitric oxide and cytokine production of 3D-cultured macrophages, compared to conventional two-dimensional (2D)-cultured cells. Moreover, the microgravity-induced macrophage dysfunction was not restored by transferring cells from 3D to 2D culture. However, the addition of morin sulphates/glucuronides in 3D culture compensated for the loss of macrophage function. CONCLUSION: The result presented here suggests for the first time that an immune-modulatory strategy using flavonoid supplements such as morin would benefit the health of astronauts.

Animals↗
PubMed1985

Structure elucidation of two isomeric steroids: photolytical and thermal reaction products from norethisterone studied by two-dimensional nuclear magnetic resonance.

Two-dimensional nuclear magnetic resonance was used for the structure elucidation of two isomeric photoproducts of norethisterone, a commonly used progestogen in oral contraceptives. The predominant one of the two isolated products derived from photochemical decomposition of norethisterone upon irradiation with UV-B light (280-320 nm) was 5 alpha, 17 beta-dihydroxy-19-nor-17 alpha-pregn-20-yn-3-one. The minor photoproduct appeared to be the analogous 5 beta-isomer, i.e. 5 beta, 17 beta-dihydroxy-19-nor-17 alpha-pregn-20-yn-3-one. The latter compound was also obtained from the thermal reduction of norethisterone-4 beta, 5 beta-epoxide using aluminium amalgam in isopropanol. Two-dimensional NMR appeared to be superior to mass and IR spectrometry in identifying the isomers.

Chemical Phenomena↗
PubMed2006

Spatially uniform sampling in 4-D EPR spectral-spatial imaging.

Four-dimensional EPR imaging involves a computationally intensive inversion of the sampled Radon transform. Conventionally, N-dimensional reconstructions have been carried out with N-1 stages of 2-D backprojection to exploit a dimension-dependent reduction in execution time. The huge data size of 4-D EPR imaging demands the use of a 3-stage reconstruction each consisting of 2-D backprojections. This gives three orders of magnitude reduction in computation relative to a single stage 4-D filtered backprojection. The multi-stage reconstruction, however, requires a uniform angular sampling that yields an inefficient distribution of gradient directions. We introduce a solution that involves acquisition of projections uniformly distributed in solid angle and reconstructs in three 2-D stages with the spatial uniform solid angle data set converted to uniform linear angular projections using 2-D interpolation. Images were taken from the two sampling schemes to compare the spatial resolution and the line width resolution. The degradation in the image quality due to the additional interpolation was small, and we achieved approximately 30% reduction in data acquisition time.

Algorithms↗
PubMed2003

Cortical blood flow during cerebral vasospasm after aneurysmal subarachnoid hemorrhage: three-dimensional N-isopropyl-p-[(123)I]iodoamphetamine single photon emission CT findings.

BACKGROUND AND PURPOSE: The relationship between regional cerebral blood flow (rCBF) during cerebral vasospasm after subarachnoid hemorrhage (SAH) and angiographic vasospasm and the value of rCBF in predicting vasospasm and the prognosis are not fully delineated. Our aim was to investigate the changes in extent of vasospasm-induced decreased cortical rCBF on three-dimensional (3D) displays of single photon emission CT (SPECT) findings. The clinical usefulness of these assessments was analyzed. METHODS: In 58 cases of SAH, SPECT and digital subtraction angiography were performed on the same day, 5-9 days after SAH or within 24 hours after the onset of delayed ischemic neurologic deficit (DIND). Cerebral blood flow data were assessed by measuring the area of decreased cortical rCBF on 3D SPECT images. RESULTS: The area of decreased cortical rCBF on the 3D images was significantly increased in cases with DIND (P <.001), in cases with a large infarction due to vasospasm (P =.006), and in cases with a poor prognosis after vasospasm (P =.045). These increases were also related to the type of angiographic vasospasm; the greatest decrease in cortical rCBF occurred in the combined type (combination of the peripheral and proximal types) of vasospasm, followed by cases with the peripheral type, proximal type, and no angiographic vasospasm. In cases with DIND, patchy decreased cortical rCBF areas were seen before the onset of DIND. CONCLUSION: Combined-type vasospasm leads to reductions in CBF greater than those due to isolated peripheral or proximal vasospasm. Two-dimensional and mean-hemispheric CBF analyses are less sensitive for this change than is 3D SPECT.

Adult↗
PubMed1997

Three-dimensional structure of Escherichia coli dihydrodipicolinate reductase in complex with NADH and the inhibitor 2,6-pyridinedicarboxylate.

Dihydrodipicolinate reductase catalyzes the NAD(P)H-dependent reduction of the alpha,beta-unsaturated cyclic imine dihydrodipicolinate to form the cyclic imine tetrahydrodipicolinate. The enzyme is a component of the biosynthetic pathway that leads to diaminopimelate and lysine in bacteria and higher plants. Because these pathways are unique to microorganisms and plants, they may represent attractive targets for new antimicrobial or herbicidal compounds. The three-dimensional structure of the ternary complex of Escherichia coli dihydrodipicolinate reductase with NADH and the inhibitor 2,6-pyridinedicarboxylate has been solved using a combination of molecular replacement and noncrystallographic symmetry averaging procedures and refined against 2.6 A resolution data to a crystallographic R-factor of 21.4% (Rfree is 29.7%). The native enzyme is a 120 000 molecular weight tetramer of identical subunits. The refined crystallographic model contains a tetramer, three molecules of NADH, three molecules of inhibitor, one phosphate ion, and 186 water molecules per asymmetric unit. Each subunit consists of two domains connected by two flexible hinge regions. While three of the four subunits of the tetramer have a closed conformation, in which the nicotinamide ring of the cofactor bound to the N-terminal domain and the reducible carbon of the substrate bound to the substrate binding domain are about 3.5 A away, the fourth subunit is unliganded and shows an open conformation, suggesting that the enzyme undergoes a major conformational change upon binding of both substrates. The residues involved in binding of the inhibitor and the residues involved in catalysis have been identified on the basis of the three-dimensional structure. Site-directed mutants have been used to further characterize the role of these residues in binding and catalysis. A chemical mechanism for the enzyme, based on these and previously reported data, is proposed.

Binding Sites↗
PubMed2002

Matrix-assisted laser desorption/ionization-tandem mass spectrometry with high resolution and sensitivity for identification and characterization of proteins.

Although peptide mass fingerprinting is currently the method of choice to identify proteins, the number of proteins available in databases is increasing constantly, and hence, the advantage of having sequence data on a selected peptide, in order to increase the effectiveness of database searching, is more crucial. Until recently, the ability to identify proteins based on the peptide sequence was essentially limited to the use of electrospray ionization tandem mass spectrometry (MS) methods. The recent development of new instruments with matrix-assisted laser desorption/ionization (MALDI) sources and true tandem mass spectrometry (MS/MS) capabilities creates the capacity to obtain high quality tandem mass spectra of peptides. In this work, using the new high resolution tandem time of flight MALDI-(TOF/TOF) mass spectrometer from Applied Biosystems, examples of successful identification and characterization of bovine heart proteins (SWISS-PROT entries: P02192, Q9XSC6, P13620) separated by two-dimensional electrophoresis and blotted onto polyvinylidene difluoride membrane are described. Tryptic protein digests were analyzed by MALDI-TOF to identify peptide masses afterward used for MS/MS. Subsequent high energy MALDI-TOF/TOF collision-induced dissociation spectra were recorded on selected ions. All data, both MS and MS/MS, were recorded on the same instrument. Tandem mass spectra were submitted to database searching using MS-Tag or were manually de novo sequenced. An interesting modification of a tryptophan residue, a "double oxidation", came to light during these analyses.

Animals↗
PubMed1992

Abnormal extracellular matrix and excessive growth of human adult polycystic kidney disease epithelia.

Human autosomal dominant polycystic kidney disease (ADPKD) epithelia were grown in primary monolayer cultures and their properties compared with intact kidney epithelial cultures derived from individually microdissected normal human kidney proximal convoluted tubules (PCT), proximal straight tubules (PST), and cortical collecting tubules (CCT). In vivo, ADPKD cyst epithelia exhibited a thickened basement membrane, and immunofluorescence demonstrated the presence of laminin, fibronectin, type IV collagen, and heparan sulfate proteoglycan in basement membranes and type I collagen in the interstitium. ADPKD epithelia grown in culture synthesized and secreted basally a unique, extracellular matrix that took the form of proteinaceous spheroids when the cells were grown on dried, type I collagen. Incorporation of H2[S35O4] into basement membrane extracts was increased more than ten-fold in ADPKD epithelia by comparison to normal PST and CCT. In addition to incorporation into the normal tubular basement membrane 220 kD band, radioactivity was also seen at 175 kD and 150 kD in ADPKD extracts. Growth in culture of cyst-lining ADPKD epithelia was more rapid than normal tubules, and was abnormal since there was no absolute requirement for added extracellular matrix. However, when ADPKD epithelia were grown on different, exogenous matrix protein components, a profound influence on both structure and epithelial cell proliferation was seen. Growth on a complete basement membrane three-dimensional gel derived from the Engelbreth-Holm-Swarm (EHS) sarcoma led to a reduction in the numbers of spheroids and increase in amorphous filaments. Incorporation of [3H]-thymidine into ADPKD epithelia was greater than into normal PCT, PST, and CCT and was also greatly modified by the type of extracellular matrix components provided. In studies using single matrix components, the strongest proliferative response was seen when ADPKD epithelia were plated on type I collagen greater than type IV collagen greater than fibronectin greater than laminin. These findings suggest that the excessive growth of cyst-lining epithelia may be, at least in part, a result of abnormal basement membrane and extracellular matrix production by ADPKD cells.

Basement Membrane↗
PubMed2003

Aberrant profiles of native and oxidized glycoproteins in Alzheimer plasma.

A proteomic approach was employed to elucidate possible differential expression of native and oxidized glycoproteins using pooled plasma samples derived from ten patients with sporadic Alzheimer's disease (AD) and pooled plasma samples from nine normal elderly control (NEC) subjects. The plasma samples were fractionated by sequential affinity chromatography on heparin-agarose (HepA) and concanavalin A-agarose (ConA) columns followed by separation on one-dimensional and two-dimensional polyacrylamide gels. Carbonylation (oxidation) of proteins was monitored by in-strip derivatization with 2,4-dinitrophenylhydrazine (DNP) and anti-DNP immunoblotting. Nine spots representing glycoproteins which showed enrichment or high specific oxidation indices in AD HepA-ConA 2-D gels relative to NEC samples were analyzed by matrix-assisted laser desorption-time of flight-mass spectrometry and identified with high probability (p < 0.001) as isoforms of human transferrin (Tf), hemopexin (Hpx) and alpha-1-antitrypsin (alpha-1-AT). These glycoproteins were concentrated, respectively, 5-, 6.5- and 107-fold in HepA-ConA eluates derived from AD plasma relative to the NEC samples. Specific oxidation indices of the identified Tf and Hpx isoforms in AD plasma were respectively, 7.4 and 2.8 relative to NEC. Our findings provide further evidence for systemic derangements in heme/iron/redox homeostasis and activation of the acute phase response in sporadic AD. Moreover, the data implicate isoforms of Tf, Hpx and alpha-1-AT as potential biological markers of this condition.

Alzheimer Disease↗
PubMed2005

Carbonylated proteins in bronchoalveolar lavage of patients with sarcoidosis, pulmonary fibrosis associated with systemic sclerosis and idiopathic pulmonary fibrosis.

Oxygen-derived free radicals produced by phagocytes have been postulated to contribute to lung tissue damage occurring during diffuse lung diseases (DLD). The two-dimensional electrophoretic (2-DE) analysis of bronchoalveolar lavage (BAL) protein composition revealed different protein profiles in sarcoidosis (S), idiopathic pulmonary fibrosis (IPF) and systemic sclerosis (SSc) with a significant increase of low molecular weight proteins in IPF. Some of these proteins are involved in antioxidant processes. The aims of this report were to analyse the oxidative stress occurring in patients with DLD through determination of BAL protein carbonyl content and to identify target proteins of oxidation by a proteomic approach (2-DE combined with immunoblotting with specific antibodies for carbonyl groups). Carbonylated proteins detected by enzyme-linked immunosorbent assay (ELISA) were increased in BAL of patients with S, IPF and SSc compared to healthy controls with a significant difference for S and IPF. The proteomic approach to the analysis of BAL revealed that protein carbonylation was a process involving specific carbonylation-sensitive proteins and that in IPF a greater number of proteins target of oxidation were present. In conclusion, to our knowledge, this is the first report providing a database of proteins target of oxidation in BAL of patients with sarcoidosis, idiopathic pulmonary fibrosis and systemic sclerosis.

Blotting, Western↗
PubMed2006

Protein sites of attack of N-chlorotaurine in Escherichia coli.

N-Chlorotaurine sodium (NCT) is a promising microbicidal agent for topical treatment of infections. Its targets of attack in Escherichia coli have been investigated by proteomics. Incubation in 1% NCT for 10 and 30 min revealed a change of the charge and a separation of numerous proteins into a series of spots with a different pI. Charge differences could be related to oxidation of cysteine residues to their corresponding sulfonic acids. Heat shock protein 60 appeared, while ribosome-releasing factor, d-ribose periplasmic binding protein, and malonyl-CoA transacylase spots decreased. These results indicate penetration of oxidation capacity into the bacteria and destruction of essential proteins by NCT.

Acyl-Carrier Protein S-Malonyltransferase↗
PubMed2006

Redox regulation of cyclophilin A by glutathionylation.

Using redox proteomics techniques to characterize the thiol status of proteins in human T lymphocytes, we identified cyclophilin A (CypA) as a specifically oxidized protein early after mitogen activation. CypA is an abundantly expressed cytosolic protein, target of the immunosuppressive drug cyclosporin A (CsA), for which a variety of functions has been described. In this study, we could identify CypA as a protein undergoing glutathionylation in vivo. Using MALDI-MS we identified Cys52 and Cys62 as targets of glutathionylation in T lymphocytes, and, using bioinformatic tools, we defined the reasons for the susceptibility of these residues to the modification. In addition, we found by circular dichroism spectroscopy that glutathionylation has an important impact on the secondary structure of CypA. Finally, we suggest that glutathionylation of CypA may have biological implications and that CypA may play a key role in redox regulation of immunity.

Circular Dichroism↗
PubMed2002

Homocysteine modifies development of neurulation and dorsal root ganglia in chick embryos.

BACKGROUND: The formation of the neural tube (neurulation) involves two mechanisms: primary and secondary neurulation. In chicks, there is also an overlap zone, where both mechanisms work together. Homocysteine (Hcy) may have an important teratogenic role in neural tube defects (NTD) when folic acid levels are considered normal. Recently, Hcy capability to generate NTD and modify neural crest cell migration has been demonstrated in chick embryos. This study was aimed to evaluate the effects of Hcy on neurulation and the development of the dorsal root ganglia (DRG). METHODS: Chick embryos were treated with L-Hcy thiolactone 20 micromol to produce the highest rate of survival with embryos carrying neural tube defect (NTD) in the spine. Embryos at stages (st) 3-10 were treated and harvested at st 18-23. Only externally normal embryos or those carrying spinal NTD embryos were considered. RESULTS: Histological sections of Hcy-treated embryos showed: open spina bifida (39% of embryos), more than one tube forming the spinal cord (26%), disorganized spinal cord (26%), always affecting lumbosacral regions, probably in the overlap zone. Additionally, 32% of embryos had small and continuous DRG, associated with a slimmed roof plate. Three-dimensional reconstruction showed unsegmented DRG until the C8 ganglion level. There was a 75% reduction of C3 DRG cells in treated embryos in comparison to untreated ganglia. CONCLUSION: Hcy teratogenicity in avian embryos affected the neural tube in the overlap zone, secondary neurulation and the cervical DRG.

Animals↗
PubMed1998

Re-entrant excitation initiated in models of inhomogeneous atrial tissue.

We demonstrate that a shift of the vulnerable window caused by tissue inhomogeneity can play a role in the generation of re-entrant excitation. The Earm-Hilgemann-Noble equations were incorporated into one- and two-dimensional inhomogeneous partial differential equation models of atrial tissue. Inhomogeneity was produced by a reduction of gNa over part of the medium and the vulnerable window for initiating re-entrant activity in homogeneous models determined from numerical integrations. Forty percent reduction of gNa produced little effect on the width of the vulnerable window, but the onset of the vulnerable window was delayed. The delay of the vulnerable window facilitates the initiation of re-entry at junctions between tissue with normal and reduced excitability, even though there is hardly any change in action potential duration.

Animals↗
PubMed1978

Cross-linking of Newcastle disease virus (NDV) proteins.

The proxomity and spatial relationships of the structural proteins of Newcastle disease virus (NDV) were studied by chemical cross-linking with a series of imidoesters. When the virions were reacted by the cross-linker with a distance 6.1A or longer between the functional groups and analyzed by polyacrylamide gel electrophoresis, remarkable changes were observed in the migration patterns of the viral proteins. The most striking one was the extensive decrease in the intensity of the M protein band, and although not so strikingly, glycoprotein and nucleocapsid protein bands were reduced significantly. Instead, several protein complexes appeared at and near the top of the gels. The protein complexes formed by a reversible cross-linker, dimethyl-3,3'-dithiobispropionimidate (DTBP), were analyzed by two dimensional electrophoresis; the complexes on the first-dimension cylindrical gels were cleaved by reduction with 2-mercaptoethanol and electrophoresed laterally on the second-dimension slab gels. The results indicated that homodimers of glycoprotein, nucleocapsid protein and M protein were generated under the condition of the most gentle cross-linking employed. At the same time, however, trimer and higher homopolymers of M protein were already detectable. Under the more extensive conditions, the bulk of M protein was cross-linked to form a large protein complex with very high molecular weight. Further, small but significant amounts of glycoprotein and nucleocapsid protein were always detected in this complex. These results suggest that M protein may be present in the virion in close enough proximity to interact with each other and may further have some interactions with glycoprotein and nucleocapsid protein. On the basis of these findings possible roles of M protein in virus assembly were discussed.

Dimethyl Adipimidate↗
PubMed2001

Two-dimensional gel electrophoresis of selenized yeast and autoradiography of 75Se-containing proteins.

Two-dimensional high-resolution gel electrophoresis (2DE) has been applied to the fractionation of 75Se-containing proteins in yeast, grown in 75Se-containing medium, and autoradiography was used for detection of the 75Se-containing proteins. Gel filtration and ultrafiltration were used to check whether the selenium side-chains were stable in the presence of the chemicals used for lysis and 2DE. The mass distribution of the selenium-containing proteins was estimated by use of gel filtration and the results were compared with the distribution obtained by 2DE. A 2DE map of selenium-containing proteins in yeast is presented, and compared with a total protein map of yeast.

Autoradiography↗
PubMed1977

Heterogeneity of the cold-insoluble globulin of human plasma (CIg), a circulating cell surface protein.

The cold-insoluble globulin of human plasma (CIg), a circulating cell surface protein, exists in multiple molecular forms. Most molecules are found as two chain (MR approximately 220 000 per chain) disulfide-bridged dimeric units but several minor components of smaller size have also been identified; based upon their migration rates in dodecyl sulfate gel electrophoretic experiments, the smaller molecules characterized in this study range in molecular size from 235 000 to 146 000. The component of molecular weight 235 000 apparently represents a two chain disulfide-bridged derivative of larger parent molecules (one chain of 220 000 plus a smaller remnant), whereas smaller CIg components appear to be single chain proteins. These observations plus electrophoretic analyses of samples of plasmic digests of CIg indicate that the interchain disulfide bridging in the two chain molecule is located in a segment within approx. 175 residues of the NH2- or COOH-terminus.

Dithiothreitol↗
PubMed1990

Regression of hypertensive left ventricular hypertrophy and left ventricular diastolic function.

The effect of antihypertensive therapy on regression of left ventricular hypertrophy and left ventricular diastolic function was investigated in 25 hypertensive patients for up to 18 months after initiation of treatment. Left ventricular mass index was calculated by two-dimensional echocardiography and left ventricular diastolic function assessed by transmitral pulsed doppler ultrasound. Significant reduction in left ventricular mass index was observed after 9 months of treatment. Only 13 patients had a reduction in mass greater than the intraobserver variability of the technique. There was no change in doppler indices of left ventricular diastolic function. In 7 patients who were studied for a further 9 months after regression had occurred there was still no appreciable difference in left ventricular diastolic function. These findings indicate that there is no direct relation between left ventricular mass and abnormal left ventricular diastolic function.

Adult↗
PubMed1990

Characterization of Trichinella spiralis antigens sharing an immunodominant, carbohydrate-associated determinant distinct from phosphorylcholine.

The biochemical and immunochemical characteristics of T. spiralis molecules (group II antigens) sharing an immunodominant epitope were examined. Six major proteins, ranging from 43-68 kDa, and from pI 5.0-6.3, express the determinant. Together, they account for at least 3% by weight of the total protein in L1 larval homogenate. The antigens are glycosylated. Following periodate oxidation, they reacted with biotin aminocaproyl hydrazide, and treatment with trifluoromethanesulfonic acid decreased their Mr. Deglycosylated group II antigens lost immunoreactivity with a monoclonal antibody specific for the determinant, and oligosaccharides released by treatment with mild base blocked binding of the monoclonal antibody to native antigens. The determinant on one of the group II antigens (43 kDa) was removed by N-glycanase. Neither phosphorylcholine nor antibody to phosphorylcholine interfered with monoclonal antibody binding to native group II antigens. Together, these results suggest that the immunodominant group II antigen epitope is associated with N- and O-linked oligosaccharides, and that it is not phosphorylcholine.

Amidohydrolases↗