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PubMed2006

gamma-Glutamyltransferase predicts cardiovascular death among Japanese women.

The clinical importance of gamma-glutamyltransferase (GGT) has recently been debated. Although some studies have suggested that the relationship between GGT and cardiovascular disease (CVD) mortality is independent of alcohol consumption, to our knowledge no studies have reported the relationship between GGT and CVD mortality in never-drinker subgroups. Since Japanese women are known to have a lower prevalence of alcohol consumption, we examined whether GGT predicts CVD mortality in never-drinkers. We followed 2724 Japanese men and 4122 Japanese women without prior CVD or liver dysfunction for 9.6 years and observed 83 and 82 CVD deaths, respectively. Current alcohol drinkers comprised 59% of men and 7% of women. Among women, the multiple adjusted hazard ratio (HR) for CVD mortality compared with the reference group (GGT: 1-12 U/L) was 2.88 (95% confidence interval (CI), 1.14-7.28) for the elevated group (GGT>or=50 U/L). This positive relationship was unchanged in the never-drinkers subgroup (HR for log-transformed continuous GGT, 1.62 (95% CI, 1.11-2.37)). No significant relationships were observed in men. GGT displays a strong positive association with CVD mortality among Japanese women, for whom the prevalence of ever-drinkers is very low. Exploring the significance and biological mechanisms of GGT might provide useful insights into CVD prevention.

Biomarkers↗

PubMed2006

sHSPs under temperature and pressure: the opposite behaviour of lens alpha-crystallins and yeast HSP26.

Small angle X-ray scattering was used to follow the temperature and pressure induced structural transitions of polydisperse native calf lens alpha-crystallins and recombinant human alphaB-crystallins and of monodisperse yeast HSP26. The alpha-crystallins were known to increase in size with increasing temperature, whereas HSP26 partially dissociates into dimers. SAXS intensity curves demonstrated that the average 40-mer calf alpha-crystallin converted into 80-mer in a narrow temperature range, from 60 to 69 degrees C, whereas the average 30-mer alphaB-crystallin was continuously transformed into 60-mer at lower temperature, from 40 to 60 degrees C. These temperature-induced transitions were irreversible. Similar transitions, yet reversible, could be induced with pressure in the 100 to 300 MPa pressure range. Moreover, temperature and pressure could be combined to lower the transition temperatures. On the other hand, SAXS curves recorded during pressure scans from 0.1 to 200 MPa with monodisperse 24-mer HSP26 revealed dissociation of the 24-mer into dimers. This dissociation was complete and reversible. Whatever the sHSP, a decrease of partial specific volume was found to be associated with the pressure induced quaternary structure transitions, in agreement with the hypothesis that such transitions represent a first step on the protein denaturation pathway.

Animals↗

PubMed2006

Cell shape and cell division.

The correlation between cell shape elongation and the orientation of the division axis described by early cell biologists is still used as a paradigm in developmental studies. However, analysis of early embryo development and tissue morphogenesis has highlighted the role of the spatial distribution of cortical cues able to guide spindle orientation. In vitro studies of cell division have revealed similar mechanisms. Recent data support the possibility that the orientation of cell division in mammalian cells is dominated by cell adhesion and the associated traction forces developed in interphase. Cell shape is a manifestation of these adhesive and tensional patterns. These patterns control the spatial distribution of cortical signals and thereby guide spindle orientation and daughter cell positioning. From these data, cell division appears to be a continuous transformation ensuring the maintenance of tissue mechanical integrity.

Animals↗

PubMed2006

In addition to obesity and insulin resistance, microalbuminuria and diminished insulin secretion are linked with the metabolic syndrome in community-dwelling nondiabetic Taiwanese subjects.

Although insulin resistance and obesity are currently considered primary factors underlying development of the metabolic syndrome, microalbuminuria and inadequate insulin secretion may also be involved. The present study is the first to examine intercorrelations among these factors in a community-based Taiwanese population. An epidemiological survey of chronic diseases conducted in 1996 was utilized to evaluate 1340 community-dwelling, nondiabetic adults. Principal component factor analyses involving varimax orthogonal rotation of transformed continuously distributed variables were performed. Sex-specific factor analyses yielded four separate factors in women (obesity/insulin resistance, lipid, blood pressure and insulin resistance/secretion factors) and three in men (obesity/insulin resistance/secretion, lipid and blood pressure factors). For men the corrected insulin response clustered with obesity, and insulin resistance loaded on the same factor, explaining 31% of variance; however, microalbuminuria was closely linked with blood pressure variables, and the corrected insulin response loaded on the same factor, explaining 13.2% of variance. Obesity and insulin resistance were confirmed as central anomalies of all features of the metabolic syndrome. The observed linkage of impaired beta-cell function and microalbuminuria with the metabolic syndrome should facilitate prediction of the onset of cardio-vasculo-metabolic disorders. Inadequate beta-cell function and microalbuminuria are plausible components of the metabolic syndrome in Taiwanese subjects.

Adult↗

PubMed2005

A direct comparison of the natriuretic peptides and their relationship to survival in chronic heart failure of a presumed non-ischaemic origin.

The natriuretic peptides have been validated as sensitive and specific markers of left ventricular dysfunction; brain natriuretic peptide (BNP), N-terminal atrial natriuretic peptide (NT-proANP) and N-terminal brain natriuretic peptide (NT-proBNP) elevations have been associated with New York Heart Association (NYHA) Class I-IV heart failure. We directly compared the association of each of these markers with 1-year survival in 173 patients with chronic heart failure of a presumed nonischaemic origin entering the PRAISE-2 Trial, a clinical study which assessed the therapeutic effect of Amlodipine in patients with NYHA Class III and IV heart failure and a left ventricular ejection fraction (LVEF) <30%. BNP, NT-proBNP, and NT-proANP levels were all correlated with 1-year mortality by univariate Cox proportional hazards analyses. With respect to multivariate Cox proportional hazards regression models containing variables deemed significant in univariate analyses, NT-proANP alone was identified as an independent predictor of 1-year mortality when log-transformed continuous covariates were utilized in the analysis. When the analysis was repeated using dichotomous covariates, NT-proANP remained the most significant predictor of 1-year mortality, followed by NT-proBNP, NYHA classification and BNP. We conclude that all three natriuretic peptides are significant predictors of short-term mortality in subjects with chronic congestive heart failure (CHF) of a presumed nonischaemic origin. Larger prospective studies are required to validate the clinical utility of NT-proANP as a discriminating marker of short-term survival, and to validate proposed cutoffs of approximately 2300 pmol/l for NT-proANP, 1500 pg/ml for NT-proBNP, and 50 pmol/l for BNP as prognostic indicators of adverse short-term outcome.

Aged↗

PubMed2005

Emission of ammonia from indoor concrete wall and assessment of human exposure.

Addition of urea-based antifreeze admixtures during cement mixing can make it possible to produce concrete cement in construction of buildings in cold weather; this, however, has led to increasing indoor air pollution due to continuous transformation and emission from urea to gaseous ammonia in indoor concrete wall. It is believed that ammonia is harmful to human body and exposure to ammonia can cause some serious symptoms such as headaches, burns, and even permanent damage to the eyes and lungs. In order to understand the emission of ammonia from indoor concrete wall in civil building and assess the health risk of people living in these buildings, the experimental pieces of concrete wall were first prepared by concreting cement and urea-based antifreeze admixtures to simulate the indoor wall in civil building in this work. Then environmental chamber was adopted for studying the effect of temperature, relative humility and air exchange rate on emission of ammonia from experimental pieces of concrete wall. Also the field experiment was made at selected rooms in given civil buildings. Exposure and potential dose of adult and children exposed to indoor/outdoor ammonia in summer and in winter are calculated and evaluated by using Scenario Evaluation Approach. The results indicated that high air exchange rate leads to decreased ammonia concentration, and elevation of temperature causes increasing ammonia concentration and volatilizing rate in chamber. The complete emission of ammonia from the wall containing urea-based antifreeze admixtures needs more than 10 years in general. Ventilating or improving air exchange can play a significant role in reducing ammonia concentration in actual rooms in field experiments. Urea-based antifreeze admixtures in concrete wall can give rise to high exposure and potential dose, especially in summer. Generally, adults have a high potential dose than children, while children have personal average dose rate beyond adults in the same conditions.

Adult↗

PubMed2025

Prenatal organophosphate ester exposure and epigenetic changes at birth: a characterization of the methylome in the ECHO cohort.

BACKGROUND: Prenatal exposure to organophosphate esters (OPEs) affects multiple child health domains. Alterations to the DNA methylome are a plausible mechanism through which these changes occur. This study characterized DNA methylation signatures at birth associated with prenatal OPE biomarkers. METHODS: We included 736 mother-infant pairs from 7 sites in the Environmental influences on Child Health Outcomes (ECHO) Cohort. Five OPE biomarkers were quantified in maternal urine samples collected during the second and third trimesters and modeled as log2-transformed continuous variables. Using covariate-adjusted linear regression, we tested associations between OPE biomarkers and locus-specific, regional, and global cord blood DNA methylation changes measured by Illumina 450 K and EPIC arrays, and gestational epigenetic age measured by the Knight gestational age epigenetic clock generated with measures from the 27 K, 450 K, and EPIC arrays. When feasible, we examined relationships by sex. FINDINGS: Global hypomethylation at multiple regions was associated with BDCPP concentrations (p = 0.003 to 0.02, coef = -0.002). Differentially methylated regions annotated to PCDHGB1 and SLC43A2 were associated with BDCPP and DPHP concentrations, respectively (FDR q < 0.05). In sex-specific analyses, global hypomethylation was associated with prenatal BDCPP (p = 0.006 to 0.03, coef = -0.0003 to -0.0002) and DBUP_DIBP (p = 0.01, coef = -0.0007 to -0.0006) concentrations in females; and global hypermethylation was associated with DBUP_DIBP concentrations in males (p < 0.05, coef = 0.0004). BCETP concentrations were significantly associated with decelerated epigenetic aging at birth in females (p < 0.05, coef = -0.05). INTERPRETATION: Prenatal exposure to OPEs impacts child methylation at birth, suggesting a potential mechanism for the association between prenatal OPE exposure and child health outcomes.

Humans↗

PubMed2006

A sub-second fast Fourier transform-adsorptive voltammetric technique for the nano-level determination of guthion at a gold microelectrode in flowing solutions.

This research demonstrates the quick guthion monitoring with the help of a sensitive method called fast Fourier transformation continuous cyclic voltammetry (FFTCV). Fortunately, FFTCV illustrates the benefits of precision, determination speed, cost-effectiveness, accuracy and simplicity, in comparison with formerly reported techniques. In particular, this method was applied to a gold microelectrode in flowing solutions to detect the guthion concentration in its formulations. The effects of several parameters were examined regarding the sensitivity of the method. After a series of experiments, the detection limit of the method was found to be equal to 1.27 pg/mL, when the optimum conditions were imposed, which is a scan rate value of 40V/s, an accumulation time of 0.4s, an accumulation potential of 0mV and a pH value of 2. During the measurements performance, the integration range of currents included all the potential scan ranges, even the oxidation and reduction of the Au surface electrode, for the achievement of a sensitive determination. Then, the potential waveform, consisting of the potential steps for cleaning, accumulation and the step for the potential ramp, was applied to an Au disk microelectrode in a continuous way. It is also important to refer to the positive points, presented only by the use of this technique. Firstly, it is no longer necessary to remove the oxygen from the test solution. Furthermore, the quick determination of any such compound in many chromatographic methods is possible. Thirdly, the corresponding detection limit is of nanomolar level.

Azinphosmethyl↗

PubMed2006

Invariant visual object recognition: a model, with lighting invariance.

How are invariant representations of objects formed in the visual cortex? We describe a neurophysiological and computational approach which focusses on a feature hierarchy model in which invariant representations can be built by self-organizing learning based on the statistics of the visual input. The model can use temporal continuity in an associative synaptic learning rule with a short term memory trace, and/or it can use spatial continuity in Continuous Transformation learning. The model of visual processing in the ventral cortical stream can build representations of objects that are invariant with respect to translation, view, size, and in this paper we show also lighting. The model has been extended to provide an account of invariant representations in the dorsal visual system of the global motion produced by objects such as looming, rotation, and object-based movement. The model has been extended to incorporate top-down feedback connections to model the control of attention by biased competition in for example spatial and object search tasks. The model has also been extended to account for how the visual system can select single objects in complex visual scenes, and how multiple objects can be represented in a scene.

Animals↗

PubMed2004

A deformable digital brain atlas system according to Talairach and Tournoux.

Brain atlases are valuable tools which assist neurosurgeons during the planning of an intervention. Since a printed atlas book has several disadvantages-among them the difficulty to map the information onto a patient's individual anatomy-we have developed a digital version of the well-established stereotaxic brain atlas of Talairach and Tournoux. Our atlas system is mainly dedicated to assist neurosurgical planning, and its benefits are: (i) a three-dimensional (3D) representation of most brain structures contained in the Talairach atlas; (ii) a nonrigid matching capability which warps the standard atlas anatomy to an individual brain magnetic resonance imaging (MRI) dataset in a few minutes and which is able to take deformations due to tumors into account; (iii) the integration of several sources of neuroanatomical knowledge; (iv) an interface to a navigation system which allows utilization of atlas information intraoperatively. In this paper we outline the algorithm we have developed to achieve 3D surface models of the brain structures. Moreover, we describe the nonrigid matching method which consists of two tasks: firstly, point correspondences between the atlas and the patient are established in an automatic fashion, and secondly these displacement vectors are interpolated using a radial basis function approach to form a continuous transformation function. To generate appropriate target structures for the first of these tasks, we implemented a quick segmentation tool which is capable to segment the cortex and ventricles in less than 5 min. An evaluation shows that our nonrigid approach is more precise than the conventional piecewise linear matching, though it should be further improved for the region around the deep grey nuclei. Summarizing, we developed a Win32 program which permits the convenient and fast application of standardized anatomy to individual brains which potentially contain tumors.

Algorithms↗

PubMed2000

Stability of a melittin pore in a lipid bilayer: a molecular dynamics study.

We have investigated the configuration and the stability of a single membrane pore bound by four melittin molecules and embedded in a fully hydrated bilayer lipid membrane. We used molecular dynamics simulations up to 5.8 ns. It is found that the initial tetrameric configuration decays with increasing time into a stable trimer and one monomer. This continuous transformation is accompanied by a lateral expansion of the aqueous pore exhibiting a final size comparable to experimental findings. The expansion-induced formation of an interface between the pore-lining acyl chains of the lipids and the pore water ("hydrophobic pore") is transformed into an energetically more favorable toroidal pore structure where some lipid heads are translocated from the rim to the central part of the interface ("hydrophilic pore"). The expansion of the pore is supported by the electrostatic repulsion among the alpha-helices. It is hypothesized that pore growth, and hence cell lysis, is induced by a melittin-mediated line tension of the pore.

Amino Acid Sequence↗

PubMed2003

Membrane fission: model for intermediate structures.

Membrane budding-fission is a fundamental process generating intracellular carriers of proteins. Earlier works were focused only on formation of coated buds connected to the initial membrane by narrow membrane necks. We present the theoretical analysis of the whole pathway of budding-fission, including the crucial stage where the membrane neck undergoes fission and the carrier separates from the donor membrane. We consider two successive intermediates of the reaction: 1), a constricted membrane neck coming out of aperture of the assembling protein coat, and 2), hemifission intermediate resulting from self-fusion of the inner monolayer of the neck, while its outer monolayer remains continuous. Transformation of the constricted neck into the hemifission intermediate is driven by the membrane stress produced in the neck by the protein coat. Although apparently similar to hemifusion, the fission is predicted to have an opposite dependence on the monolayer spontaneous curvature. Analysis of the further stages of the process demonstrates that in all practically important cases the hemifission intermediate decays spontaneously into two separate membranes, thereby completing the fission process. We formulate the "job description" for fission proteins by calculating the energy they have to deliver and the radii of the protein coat aperture which have to be reached to drive the fission process.

Cell Surface Extensions↗

PubMed1996

X-ray structure determination of fully hydrated L alpha phase dipalmitoylphosphatidylcholine bilayers.

Bilayer form factors obtained from x-ray scattering data taken with high instrumental resolution are reported for multilamellar vesicles of L alpha phase lipid bilayers of dipalmitoylphosphatidylcholine at 50 degrees C under varying osmotic pressure. Artifacts in the magnitudes of the form factors due to liquid crystalline fluctuations have been eliminated by using modified Caillé theory. The Caillé fluctuation parameter eta 1 increases systematically with increasing lamellar D spacing and this explains why some higher order peaks are unobservable for the larger D spacings. The corrected form factors fall on one smooth continuous transform F(q); this shows that the bilayer does not change shape as D decreases from 67.2 A (fully hydrated) to 60.9 A. The distance between headgroup peaks is obtained from Fourier reconstruction of samples with four orders of diffraction and from electron density models that use 38 independent form factors. By combining these results with previous gel phase results, area AF per lipid molecule and other structural quantities are obtained for the fluid L alpha phase. Comparison with results that we derived from previous neutron diffraction data is excellent, and we conclude from diffraction studies that AF = 62.9 +/- 1.3 A2, which is in excellent agreement with a previous estimate from NMR data.

1,2-Dipalmitoylphosphatidylcholine↗

PubMed2000

A new method for determining the phase in the X-ray diffraction structure analysis of phosphatidylcholine/alcohol.

A new method based on a sampling theorem is proposed for determining the phase in the X-ray diffraction analysis of the structure of phospholipid systems. The thickness of a lipid layer is changed by changing the length of hydrocarbon chains in order to rebuild the continuous transform from the scattering amplitudes. By employing this method, the phases were accurately determined in a structure analysis of nine phospholipid/alcohol systems at the interdigitated gel phase. The nine systems are dimyristoylphosphatidylcholine(DMPC)/propanol, DPPC/methanol, DPPC/ethanol, DPPC/propanol, DPPC/butanol, distearoylphosphatidylcholine(DSPC)/methanol, DSPC/ethanol, DSPC/propanol and DSPC butanol systems.

Alcohols↗

PubMed1998

Fluid phase structure of EPC and DMPC bilayers.

X-ray diffraction data taken at high instrumental resolution were obtained for EPC and DMPC under various osmotic pressures, primarily at T = 30 degrees C. The headgroup thickness DHH was obtained from relative electron density profiles. By using volumetric results and by comparing to gel phase DPPC we obtain areas AEPCF = 69.4 +/- 1.1 A2 and ADMPCF = 59.7 +/- 0.2 A2. The analysis also gives estimates for the areal compressibility KA. The AF results lead to other structural results regarding membrane thickness and associated waters. Using the recently determined absolute electrons density profile of DPPC, the AF results also lead to absolute electron density profiles and absolute continuous transforms magnitude of F(q) for EPC and DMPC. Limited measurements of temperature dependence show directly that fluctuations increase with increasing temperature and that a small decrease in bending modulus KC accounts for the increased water spacing reported by Simon et al. (1995) Biophys. J. 69, 1473-1483.

Dimyristoylphosphatidylcholine↗

PubMed1981

Cellular localization of AFP, hCG and its free subunits, and SP1 in embryonal carcinoma of the testis and ovary.

An immunohistological study of AFP, hCG and its free subunits, and SP1 was investigated in 10 cases of non-seminomatous germ cell tumors of the testis and ovary. AFP was demonstrated in mononuclear embryonal tumor cells within embryonal carcinoma in a narrow sense, frequently in association with yolk sac tumor. AFP was more consistently demonstrated in vacuolated or elongated cells of yolk sac tumor, in which continuous transformation from tubular patterns of embryonal carcinoma was shown with positive reactions for AFP. The hCG was demonstrated in syncytiotrophoblastic giant cells scattered among the embryonal carcinoma, but rarely in mononuclear large cells. The occurrence of hCG and beta subunit was more frequently observed than a subunit or SP1, suggesting the unbalanced synthesis of hCG and free subunit in choriocarcinomatous element associated with embryonal carcinoma. These findings support the view that embryonal carcinoma has a developmental potential to the extra-embryonic components of both choriocarcinoma and yolk sac tumor.

Adolescent↗

PubMed1998

Kampanols: novel Ras farnesyl-protein transferase inhibitors from Stachybotrys kampalensis.

Farnesyl-protein transferase (FPTase) is a critical enzyme that participates in the post-translational modification of the Ras protein. Inhibitors of this enzyme have the potential of being novel anticancer agents for tumors in which the ras oncogene is found mutated and contributes to cell transformation. Continued screening of natural product extracts led to the isolation of kampanols, which are novel and specific inhibitors of FPTase. The most active kampanols exhibited IC50 values between 7 to 13 microM against human recombinant FPTase. The isolation, structure determination, and biological activity of these compounds are described.

Alkyl and Aryl Transferases↗

PubMed2003

Calculation of dipole-shielding polarizabilities (sigma(alphabetagamma)I): the influence of uniform electric field effects on the shielding of backbone nuclei in proteins.

A significant contribution to the chemical shielding of a nucleus can arise from uniform electric fields that act to distort the electronic charge distribution surrounding a nucleus and, hence, affect the nuclear shielding. It has been shown by Buckingham (Buckingham, A. D. Can. J. Chem. 1960, 38, 300) that the nuclear magnetic shielding tensor sigmaalphabetaI of a nucleus in the presence of an external weak static uniform electric field E may be expanded using sigmaalphabetaI(E) = sigmaalphabetaI + sigmaalphabetagammaIEgamma + 1/2sigmaalphabetagammadeltaIEgammaEdelta + sigmaalphabeta,gammadeltaIEgammadelta ... The third rank tensor sigmaalphabetagammaI is referred to as the dipole-shielding polarizability and describes the nonlinear response of the electron cloud to first order in E, muI, and B0. We report calculations of sigmaalphabetagammaI for the N, HN, and C' nuclei in N-methyl acetamide (NMA) and show that these tensors can be used to provide considerable insight into the behavior of uniform electric fields upon the shielding of backbone nuclei in proteins. The sigmaalphabetagammaI values for the N, HN, and C' of NMA were calculated using the continuous transformation of the origin of the current density (CTOCD) scheme with the diamagnetic contribution set to zero (CTOCD-DZ). Values are given for the individual tensor components of sigmaalphabetagammaI for each nucleus. To test that the calculations have provided a reasonable estimate for the sigmaalphabetagammaI of N, HN, and C' nuclei in proteins, a pH titration was performed using Hen Lysozyme (HEWL). The pH-induced isotropic shielding changes for the C', N, and HN nuclei in some peptide bonds close to E35 ( approximately <8 A) were extracted from sets of fitted titration curves. Assuming the experimental shielding changes arise solely from uniform electric field effects caused by the deprotonation of E35, without any other pH-induced structural alterations which might lead to a shielding change, the experimental shielding differences were compared to those calculated via the product Agamma(I).Egamma where Agamma(I) = (1/3)sigmaalphaalphagammaIota. The agreement with the experimental data is in many cases reasonable and suggests that, within the Buckingham formalism, the complete sigmaalphabetagammaI tensors reported here will be helpful to resolve the importance of uniform electric fields upon isotropic and anisotropic shielding in proteins and their complexes.

Acetamides↗