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Biomedical subjects

Z Chen

Publications and source records attributed to Z Chen.

At least 631 records · Page 35Linked to original sources

Usual dietary consumption of soy foods and its correlation with the excretion rate of isoflavonoids in overnight urine samples among Chinese women in Shanghai.

Soy foods and certain soy constituents, particularly isoflavones, have been suggested to have potential cancer-inhibitory effects in laboratory and epidemiological studies. Chinese women in Shanghai consume high levels of soy foods and have low incidence rates of breast and other hormone-related cancers. To assess the usual dietary consumption of soy foods and evaluate the correlation of soy food consumption with the urinary excretion of isoflavonoids in overnight urine samples in this population, we analyzed data from 60 healthy women included in an ongoing population-based case-control study of breast cancer in Shanghai. Usual consumption of soy foods in the previous five-year period was assessed using a food-frequency questionnaire, and urinary excretion of daidzein, genistein, glycitein, equol, and O-desmethylangolensin was measured from overnight urine samples collected at the time of dietary assessment. Virtually all women (96.7%) in Shanghai consumed soy foods at least once a week. The median intake of soy food was 100.6 g/day, with 25th and 75th percentiles of 36.8 and 238.2 g, respectively. The median intake of isoflavones was 39.26 mg/day, and there was a nearly fourfold difference between the 25th and 75th percentiles of this measurement. With the increasing intake of soy foods, urinary excretion rates of total isoflavonoids and all individual major isoflavonoids were increased in a dose-response manner (trend test p < or = 0.05). At individual levels the urinary excretion rate of total isoflavonoids was correlated closely with dietary soy food intake, with a correlation coefficient of around 0.5 (p < 0.001). These results indicate that the urinary excretion rate of total isoflavonoids measured from overnight urine samples may reflect reasonably well the usual intake of soy foods in a population with a high level of soy food consumption.

Adult↗

Two new diterpenoids from Mallotus apelta Muell.Arg.

Two new diterpenoids, malloapeltene (6,8-dihydroxy-cembrene-5-one) and malloapeltin (4alpha,15,16-trihydroxy-dolabradane) were isolated and characterized from the petroleum ether fraction of the alcoholic extract of Mallotus apelta Muell.Arg. Their structures were determined by spectral methods.

Diterpenes↗

Triterpenoid saponins from Vaccaria segetalis.

A new triterpenoid saponin, named segetoside C (1), and two known saponins, vaccaroid A (vaccaroside A) (2) and dianoside G (3), have been isolated from the seeds of Vaccaria segetalis. On the basis of chemical reaction and spectral data, the structure of segetoside C (1) has been established as: gypsogenic acid-28-O-[beta-D-glucopyranosyl-(1-->3)]-[6-O-acetyl-beta-D-glucopyra-nosyl-(1-->2)-beta-D-glucopyranosyl-(1-->6)]-beta-D-glucopyranoside.

Carbohydrate Sequence↗

Y-Chromosome evidence for a northward migration of modern humans into Eastern Asia during the last Ice Age.

The timing and nature of the arrival and the subsequent expansion of modern humans into eastern Asia remains controversial. Using Y-chromosome biallelic markers, we investigated the ancient human-migration patterns in eastern Asia. Our data indicate that southern populations in eastern Asia are much more polymorphic than northern populations, which have only a subset of the southern haplotypes. This pattern indicates that the first settlement of modern humans in eastern Asia occurred in mainland Southeast Asia during the last Ice Age, coinciding with the absence of human fossils in eastern Asia, 50,000-100,000 years ago. After the initial peopling, a great northward migration extended into northern China and Siberia.

Africa↗

Diet and health risk: risk patterns and disease-specific associations.

Whether such epidemiologic descriptors as relative risk, dose response, and threshold points convey meaningful information is often the subject of debate. Thus, using these descriptors to juxtapose the many disease-specific effects of nutritional exposures becomes problematic. In this article it is argued that epidemiologic patterns of disease-exposure associations must be interpreted in light of the profound imprecision of exposure assessment that characterizes nutritional epidemiology. In general, this imprecision leads to substantial attenuation of disease-exposure associations, such that relative risk, dose response, and the extent to which there are thresholds in disease-exposure associations can be seriously underestimated. Linking disease-specific relative risks, especially when derived from different studies with different methods of assessing exposure, is made increasingly difficult. The most critical tasks for lessening bias in these epidemiologic descriptors are first, to lessen imprecision in measuring exposures, and second, to adjust association estimates for attenuation due to measurement imprecision.

Diet↗

Synergistic effect of paclitaxel and 4-hydroxytamoxifen on estrogen receptor-negative colon cancer and lung cancer cell lines.

Antiestrogen tamoxifen (Tam) is the most prescribed drug for the treatment of estrogen receptor (ER)-positive breast cancers. It is also used in long-term clinical trials with encouraging preliminary results as a chemopreventive agent for breast cancer. The effect of Tam on ER-negative cancers, however, is unclear. Here we reported that paclitaxel and 4-hydroxytamoxifen (4-HT) have a synergistic cytotoxic effect on the ER-negative colon cancer cell line HCT15, which is refractory to paclitaxel alone. Our results showed that 4-HT at submicromolar concentrations effectively enhanced the antiproliferative effect of paclitaxel. In addition, at 1/10 of the paclitaxel concentrations used for HCT15, 4-HT and paclitaxel also showed synergistic effect on NCI H460, an ER-negative lung cancer cell line. For both cell lines, the effective concentration for paclitaxel to inhibit cell growth was 1 log lower in the combination treatment than the concentration used in the single treatment. Cell cycle analysis showed that the combination of paclitaxel and 4-HT increased the G2/M population and resulted in the increase of apoptosis in both cell lines. Enhanced early release of cytochrome c from mitochondria may be the apoptotic pathway activated in the combination treatment in HCT15 cells.

Adenocarcinoma↗

Dark incoherent soliton splitting and "phase-memory" effects: Theory and experiment.

We report on an experimental observation of dark incoherent soliton Y splitting. The effects of incoherence on the evolution of incoherent dark soliton doublets are investigated both theoretically and experimentally. We show that the dynamics of these incoherent self-trapped entities are associated with strong "phase-memory" effects that are otherwise absent in the linear regime.

Journal Article↗

Salicylic acid induces rapid inhibition of mitochondrial electron transport and oxidative phosphorylation in tobacco cells

Salicylic acid (SA) is known to induce alternative pathway respiration by activating expression of the alternative oxidase gene. In the present study we report a rapid mode of action by SA on plant mitochondrial functions. SA at concentrations as low as 20 &mgr;M induced inhibition of both ATP synthesis and respiratory O2 uptake within minutes of incubation in tobacco (Nicotiana tabacum) cell cultures. Biologically active SA analogs capable of inducing pathogenesis-related genes and enhanced resistance also caused rapid inhibition of ATP synthesis and respiratory O2 uptake, whereas biologically inactive analogs did not. Inhibition of ATP synthesis and respiratory O2 uptake by SA was insensitive to the protein synthesis inhibitor cycloheximide, but was substantially reduced by the antioxidant N-acetylcysteine, suggesting a possible role for reactive oxygen species in the inhibition of mitochondrial functions. With exogenous NADH as the respiratory substrate, mitochondria isolated from SA-treated tobacco cell cultures were found to have normal capacities for both ATP synthesis and respiratory O2 uptake; direct incubation of isolated mitochondria with SA had no significant effect on these mitochondrial functions. These results indicate that (a) the respiration capacities of isolated mitochondria do not correspond to the in vivo respiration activities in SA-treated cell cultures and (b) the SA-induced inhibition of respiration in tobacco cell cultures may involve other components that are not present in isolated mitochondria. Given the recently demonstrated roles of mitochondria in plant disease resistance and animal apoptosis, this rapid inhibition by SA of mitochondrial functions may play a role in SA-mediated biological processes, including plant defense responses.

Journal Article↗

Real-space molecular-dynamics structure refinement.

Real-space targets and molecular-dynamics search protocols have been combined to improve the convergence of macromolecular atomic refinement. This was accomplished by providing a local real-space target function for the molecular-dynamics program X-PLOR. With poor isomorphous replacement experimental phases, molecular dynamics does not improve real-space refinement. However, with high-quality anomalous diffraction phases convergence is improved at the start of refinement, and torsion-angle real-space molecular dynamics performs better than other available least-squares or maximum-likelihood methods in real or reciprocal space. It is shown that the improvements result from an optimization method that can escape local minima and from a reduction of overfitting through the implicit use of phases and through use of a local refinement in which errors in remote parts of the structure cannot be mutually compensating.

Hydroxymethylglutaryl CoA Reductases↗

Critical initial real-space refinement in the structure determination of arginine kinase.

Arginine kinase (AK), a homologue of creatine kinase, catalyses the reversible transfer of a phosphoryl group between a guanidino phosphate and ADP. The family of phosphagen kinases eluded structure determination for over 25 years until an inactive form creatine kinase (CK) structure was determined [Fritz-Wolf et al. (1996). Nature (London), 381, 341-345]. The structure determination of the active-form transition-state complex was non-trivial, owing to the distant relatedness and domain reorientation of AK compared with CK. Phases from a molecular-replacement solution of the large domain, supplemented by single isomorphous replacement and inter-crystal averaging, did not reveal interpretable electron density for the small domain. Reciprocal-space refinement of the initial model (Rfree = 0.54) by any of the commonly used methods, including post facto application of maximum-likelihood methods, led to overfitting without significant improvement of the partial initial model. By contrast, in the local real-space refinements which proved successful, the interdependence of atoms is limited to immediate neighbors, and atomic positions are not influenced by errors or omissions in remote parts of the structure. Modest improvement was possible without overfitting, and this was critical to the calculation of improved phases. Phases were refined and extended from 4.0 to 2.5 A resolution by Fourier inversion of omit maps, combination with isomorphous replacement phases and averaging between crystal forms, after several batches of real- and reciprocal-space atomic refinement. The final structure refinement, against a 1.86 A cryo data set yielded a high-quality model with R = 0.196 and Rfree = 0.224.

Arginine Kinase↗

Purification, solution properties and crystallization of SIV integrase containing a continuous core and C-terminal domain.

The C-terminal two-thirds segment of integrase derived from the simian immunodeficiency virus has been cloned, expressed in Escherichia coli, and purified to greater than 95% homogeneity. The protein encompasses amino-acid residues 50-293 and contains a F185H substitution to enhance solubility. In dilute solutions at concentrations below 1 mg ml(-1), the enzyme is predominantly dimeric. At the higher concentrations (>10 mg ml(-1)) required to enable crystallization, the enzyme self-associates to form species with molecular weights greater than 200 kDa. Despite the apparent high aggregation in solution, the enzyme crystallizes from a 8%(v/v) polyethylene glycol (molecular weight 6000) solution in a form suitable for X-ray diffraction studies. The resulting single crystals belong to the space group P2(1)2(1)2(1), with unit-cell parameters a = 79.76, b = 99.98, c = 150.2 A, alpha = beta = gamma = 90 degrees and Z = 4. Under X-ray irradiation generated with a rotating-anode generator, the crystals diffract to 2.8 A resolution and allow collection of a native 3 A resolution diffraction data set.

Cloning, Molecular↗

Crystallization and preliminary diffraction studies of two quinoprotein alcohol dehydrogenases (ADHs): a soluble monomeric ADH from Pseudomonas putida HK5 (ADH-IIB) and a heterotrimeric membrane-bound ADH from Gluconobacter suboxydans (ADH-GS).

Crystals of a soluble monomeric quinocytochrome alcohol dehydrogenase (ADH-IIB) and of a trimeric membrane-associated quinocytochrome alcohol dehydrogenase (ADH-GS) have been obtained. The ADH-IIB crystals are triclinic, with one monomer in the unit cell, and were obtained in the presence of PEG 8000, sodium citrate, HEPES buffer and 2-propanol. X-ray data were collected at 110 K to 1. 9 A resolution (R(merge) = 6.4%) and the orientation of a methanol dehydrogenase search molecule (from Methylophilus methylotrophus W3A1) was obtained by molecular replacement. Preliminary refinement of this model (10.0-3.0 A resolution, R = 0.37, R(free) = 0.40) led to tentative identification of the two highest peaks in a native anomalous difference Fourier map as the Fe atom of the heme and a calcium ion interacting with the PQQ prosthetic group. The ADH-GS crystals are tetragonal, displaying six similar lattices, both primitive and centered, and were grown by the sitting-drop method after replacement of Triton X-100 by dodecylmaltoside or octaethylene glycol monododecyl ether in the presence of ammonium sulfate and sodium acetate buffer, with and without PEG 3500 and calcium ion. The best diffraction is obtained at 110 K where the resolution extends to about 4 A in the a and b directions and about 3 A in the c direction.

Alcohol Oxidoreductases↗

Combined use of transverse and scout computed tomography scans to localize radioactive seeds in an interstitial brachytherapy implant.

Various techniques have been developed to localize radioactive sources in brachytherapy implants. The most common methods include the orthogonal film method, the stereo-shift film method, and recently, direct localization from a series of contiguous CT transverse images. The major advantage of the CT method is that it provides the seed locations relative to anatomic structures. However, it is often the case that accurate identification and localization of the sources become difficult because of partial source artifacts in more than one transverse cut and other artifacts on CT images. A new algorithm has been developed to combine the advantages of using a pair of orthogonal scout views with the advantages of using a stack of transverse cuts. In the new algorithm, a common reference point is used to correlate CT transverse images and two orthogonal scout CT scans (AP and lateral). The radioactive sources are localized on CT transverse images. At the same time, the sources are displayed automatically on the two CT scout scans. In this way, the individual sources can be clearly distinguished and ambiguities arising from partial source artifacts are resolved immediately. Because of the finite slice thickness of transverse cuts, the longitudinal coordinates are more accurately obtained from the scout views. Therefore, the longitudinal coordinates of seeds localized on the transverse cuts are adjusted so that they match the position of the seeds on scout views. The algorithm has been tested on clinical cases and has proved to be a time saving and accurate method.

Adult↗

Herpes simplex virus inhibits apoptosis through the action of two genes, Us5 and Us3.

Apoptosis of virus-infected cells occurs either as a direct response to viral infection or upon recognition of infection by the host immune response. Apoptosis reduces production of new virus from these cells, and therefore viruses have evolved inhibitory mechanisms. We previously showed that laboratory strains of herpes simplex virus type 1 (HSV-1) protect infected cells from apoptosis induced by cytotoxic T lymphocytes or ethanol. We have now evaluated the ability of HSV-1 and HSV-2 laboratory and clinical isolates to inhibit apoptosis induced by anti-Fas antibody or UV irradiation and explored the genetic basis for this inhibition. HSV-1 isolates inhibited apoptosis induced by UV or anti-Fas antibody. In contrast, HSV-2 clinical isolates failed to inhibit apoptosis induced by either stimulus, although the HSV-2 laboratory strain 333 had a partial inhibitory effect on UV-induced apoptosis. Inhibition of apoptosis by HSV was accompanied by marked reduction of caspase-3 and caspase-8 activity. Deletion of the HSV-1 Us3 gene markedly reduced inhibition of UV-induced apoptosis and partially abrogated inhibition of Fas-mediated apoptosis. Conversely, deletion of the HSV-1 Us5 gene markedly reduced protection from Fas-mediated apoptosis and partially abrogated protection from UV. The Us11 and Us12 genes were not necessary for protection from apoptosis induced by either stimulus. The differences between HSV-1 and HSV-2 in the ability to inhibit apoptosis may be factors in the immunobiology of HSV infections.

Animals↗

Nitric oxide synthase isoform expression in the developing lung epithelium.

Nitric oxide (NO), generated by NO synthase (NOS), is an important mediator of physiological processes in the airway and lung parenchyma, and there is evidence that the pulmonary expression of the endothelial isoform of NOS (eNOS) is developmentally regulated. The purpose of the present study was to delineate the cellular distribution of expression of eNOS in the developing respiratory epithelium and to compare it with inducible (iNOS) and neuronal (nNOS) NOS. Immunohistochemistry was performed on fetal (125-135 days gestation, term 144 days), newborn (2-4 wk), and maternal sheep lungs. In fetal lung, eNOS expression was evident in bronchial and proximal bronchiolar epithelia but was absent in terminal and respiratory bronchioles and alveolar epithelium. Similar to eNOS, iNOS was detected in bronchial and proximal bronchiolar epithelia but not in alveolar epithelium. However, iNOS was also detected in terminal and respiratory bronchioles. nNOS was found in epithelium at all levels including the alveolar wall. iNOS and nNOS were also detected in airway and vascular smooth muscle. The cellular distribution of all three isoforms was similar in fetal, newborn, and adult lungs. Findings in the epithelium were confirmed by isoform-specific reverse transcription-polymerase chain reaction assays and NADPH diaphorase histochemistry. Thus the three NOS isoforms are commonly expressed in proximal lung epithelium and are differentially expressed in distal lung epithelium. All three isoforms may be important sources of epithelium-derived NO throughout lung development.

Animals↗

Nuclear factor-kappaB-like activity increases in murine cerebral cortex after sleep deprivation.

Several well-defined sleep regulatory substances, e.g., interleukin-1beta, activate the heterodimeric transcription factor nuclear factor-kappaB (NF-kappaB). Several substances that inhibit sleep, e.g., interleukin-4, inhibit NF-kappaB activation. NF-kappaB activation promotes production of several additional substances thought to be involved in sleep regulation, e.g., nitric oxide. We investigated, therefore, whether there are diurnal rhythms of NF-kappaB activation in brain and changes in the activation after sleep deprivation. Mice were kept on a 12:12-h light-dark cycle. In one experiment, groups of mice were killed every 3 h across the 24-h cycle. In another experiment, mice were killed at 1500 after 6 h of sleep deprivation, and a group of control mice were killed at the same time. Nuclear proteins were extracted from each brain tissue sample, and NF-kappaB-like activity was determined with an electrophoretic mobility shift assay. In cerebral cortex, but not other areas of brain, there was a diurnal rhythm in NF-kappaB-like activation; highest levels were found during the light period. NF-kappaB-like activation was higher in cerebral cortex after sleep deprivation compared with values obtained from control mice. The results are consistent with the hypothesis that sleep regulation involves multiple gene events, some of which include enhanced production of sleep regulatory substances, the actions of which involve NF-kappaB activation.

Animals↗

Preparations and properties of a novel grafted segmented polyurethane-bearing glucose groups.

Novel grafted polyurethane-bearing glucose groups were synthesized through a graft copolymerization of a prefabricated polyurethane containing poly(butadiene) glycol (PBD) and hydrogenated poly(butadiene) glycol (HPBD) soft segments, and 4,4'-methylenediphenyl diisocyanate (MDI) hard segment with a hydrophilic monomer glycosylethyl methacrylate (GEMA) in solution in the presence of 2,2'-azobis(isobutyronitrile) (AIBN) as an initiator. The bulk characteristics of the grafted polyurethanes were investigated by infra-red (IR) spectroscopy and gel permeation chromatography (GPC) measurements. The glucose groups were oriented on the surface of the cast film of grafted polyurethane with different graft-on percentages as revealed by electron spectroscopy for chemical analysis (ESCA), attenuated total reflectance infra-red spectroscopy (ATR-FTIR), and water contact angle. The grafted polyurethane surfaces which showed decreased water contact angles also indicate that hydrophilic glucose groups are present at the surface. The hemocompatibilities of these polymer surfaces were evaluated by platelet-rich plasma (PRP) contacting tests. It was found that the surface of grafted polyurethane with a graft-on percentage of 23.4% showed a good hemocompatibility in terms of platelet adhesion and shape variation. It indicates that glucose groups on the surface are effective for the improvement of hydrophilicity as well as hemocompatibility.

Animals↗