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Biomedical subjects

Z Wu

Publications and source records attributed to Z Wu.

At least 91 records · Page 5Linked to original sources

Symmetry role on the preedge X-ray absorption fine structure at the metal K edge.

The preedge features in a system with "even" symmetry, apart from quadrupolar transition contribution, are mainly dipolar in character, associated with the existence of unoccupied states made up of mixed cation-4p with higher-neighboring cation-3d orbitals, and reflect the density of states due to the medium-range order of the system. In "odd" symmetry materials these preedge features are the result of a transition from the 1s to a final density of states of p symmetry due to an unsymmetrical mixing of the ligand wave functions with the central cation 3d orbitals, similar to atetrahedral configuration. These results are validated for Fe as a photoabsorber by comparing XAS spectra of Fe2SiO4 (fayalite) to ab initio full multiple scattering calculations at the Fe K edge, but pertain to all systems containing sixfold-coordinated cations.

Journal Article↗

Oxygen 1s ELNES study of perovskites (Ca,Sr,Ba)TiO3.

The O K-edge spectra of perovskites XTiO3 with X=Ca, Sr and Ba have been measured using electron energy-loss spectroscopy (EELS) and are analyzed using the ab initio full multiple-scattering (MS) calculations. The near-edge structures arise mainly from covalency by direct and/or indirect interaction between oxygen and metal. The coordination number of the cation and the site symmetry also influence the spectral shape and structures. Comparison of full MS simulations of different clusters around the excited atom allows to interpret and correlate the features present in the spectra of each compound to its specific atomic arrangement and electronic structure.

Journal Article↗

Experimental and theoretical XANES study of the effects of Fe-Mg solid solution in the enstatite-ferrosilite series.

Synthetic orthopyroxenes in the join enstatite - ferrosilite (Mg2Si2O6-Fe2Si2O6) have been studied by XANES with the aim to interpret the variations found in the spectra and evaluate the effects of the Mg-Fe substitution in the orthopyroxene (OPX) structure. The experimental Fe- and Mg-K edge XANES spectra show variations of the peaks intensity as a function of the chemical composition of the samples along the EN-FS join. In the region of the Fe edge, the intensity ratio between peak A and B (IB/IA) varies linearly (R=0.99) with the Mg/Fe substitution. Multiple scattering calculation have been performed both at the Fe and Mg K-edge, to study the geometrical modifications of the M1 and M2 octahedral sites induced by the Mg-Fe substitutions. The spectra, obtained locating Fe (or Mg) in both M1 and M2 and weighing the contributions using the occupancy data for the M1 and M2 sites determined by XRD, allow to discriminate the effects to the total spectrum due to Fe (Mg) located in each sites separately.

Journal Article↗

Cell cycle and biochemical effects of PD 0183812. A potent inhibitor of the cyclin D-dependent kinases CDK4 and CDK6.

Progression through the G1 phase of the cell cycle requires phosphorylation of the retinoblastoma gene product (pRb) by the cyclin D-dependent kinases CDK4 and CDK6, whose activity can specifically be blocked by the CDK inhibitor p16(INK4A). Misregulation of the pRb/cyclin D/p16(INK4A) pathway is one of the most common events in human cancer and has lead to the suggestion that inhibition of cyclin D-dependent kinase activity may have therapeutic value as an anticancer treatment. Through screening of a chemical library, we initially identified the [2,3-d]pyridopyrimidines as inhibitors of CDK4. Chemical modification resulted in the identification of PD 0183812 as a potent and highly selective inhibitor of both CDK4 and CDK6 kinase activity, which is competitive with ATP. Flow cytometry experiments showed that of the cell lines tested, only those expressing pRb demonstrated a G1 arrest when treated with PD 0183812. This arrest correlated in terms of incubation time and potency with a loss of pRb phosphorylation and a block in proliferation, which was reversible. These results suggest a potential use of this chemical class of compounds as therapeutic agents in the treatment of tumors with functional pRb, possessing cell cycle aberrations in other members of the pRb/cyclin D/p16(INK4A) pathway.

Animals↗

Sino-MONICA project: a collaborative study on trends and determinants in cardiovascular diseases in China, Part i: morbidity and mortality monitoring.

BACKGROUND: The Sino-MONICA project is a 7-year study monitoring trends and determinants of cardiovascular disease (CVD) in geographically defined populations in different parts of China. METHODS AND RESULTS: The study is a community-based prospective disease surveillance that uses the methodology and criteria of the World Health Organization's Monitoring Trends and Determinants in Cardiovascular Disease (WHO MONICA) project, with slight modifications for local use. After a pilot study of 2 years (1985 through 1986), data collection started formally on January 1, 1987, and ended on December 31, 1993. The main results were as follows. By international standards, both the incidence and mortality rate of coronary heart disease in Chinese populations were low. The highest incidence was 108.7 of 100,000 (1987 to 1989), and the lowest was 3.3 of 100,000 for men 35 to 64 years of age, a 33-fold difference. Both the incidence and mortality rate of cerebrovascular disease were high. The highest incidence was 553.3 of 100,000 (1987 to 1989), and the lowest was 33.0 of 100,000 for men 35 to 64 years of age, a 17-fold difference. There were significant geographic variations in both CVD incidence and mortality rate, with higher rates in the north and lower rates in the south. During 1987 to 1993, increasing trends were found in CVD rates in some populations, whereas decreasing trends were found in others. The trends were not significant statistically in most cases. CONCLUSIONS: Monitoring CVD with international standardized methods in China is feasible and urgently needed in view of the rapid socioeconomic development and transition of disease patterns taking place in China. The results are of significance in combating CVD both at home and abroad.

Adult↗

Effect of nitric oxide on iron-mediated cytotoxicity in primary cultured renal proximal tubules.

Nitric oxide (NO) has been proved to be a mediator of hypoxic injury in renal proximal tubules (PT), but its effect on iron-induced cytotoxicity has remained little known. In this study, we observed the relationship between NO production and lactate dehydrogenase (LDH) release in primary proximal tubular epithelia co-incubated with different doses of NTA-Fe and lipopolysaccharide (LPS) alone or in combination. NO production was monitored by NO2 concentration in supernatants based on the Griess reaction; while the semi-quantitative RT-PCR was applied to detect the inducible nitric oxide synthase (iNOS) mRNA level induced by NTA-Fe and LPS together. In addition, experimental groups were subjected to reactive oxygen species (ROS) scavengers to determine the impact of the interaction between NO and ROS on iron-mediated cytotoxicity. After a 12-h co-incubation, we found that NTA-Fe increased both LDH release and NO2(-) production in a dose-dependent manner (P < 0.001). The level of iNOS mRNA induced by LPS was enhanced by 500 microM NTA-Fe (P < 0.01), lower or higher concentrations had no effect. However, the supernatantNO2(-) level in the same group did not change significantly (P > 0.05) although tubular injury was aggravated (P < 0.001). The addition of L-arginine increased LDH release from 25.05 +/- 8.36% in the iron group to 38.67 +/- 7.67% in iron plus LPS group (P < 0.05); concomitantly, L-NAME mitigated iron toxicity in LPS-treated PT (P < 0.05). Hydroxyl scavengers provided complete protection against iron-mediated cytotoxicity (P < 0.001), but the decrease of NO2(-) production was only significant in the LPS-treated group. In contrast, SOD was partially effective in the LPS group (P < 0.05) whereas the NO2(-) level in the supernatant was inversely raised (P < 0.05). GSH had no effect on either iron toxicity or NO2(-) production. Thus, we conclude that NO can exacerbate the cytotoxicity caused by NTA-Fe in cultured proximal tubular epithelia, but NO is not the only factor. NTA-Fe could enhance the upregulation of iNOS transcription induced by LPS in a specific concentration range, and its regulation of NO production might also involve a post-transcription mechanism. The hydroxyl group is the major mediator in our model and the pro-oxidant role of NO is probably due to its ability to promote the Fenton reaction and form both ONOO(-) and *OH via its interaction with ROS.

Animals↗

Karyotype, phenotype and parental origin in 19 cases of triploidy.

The parental origin of triploidy in 19 cases was examined by inheritance of DNA microsatellites and by methylation patterns of SNRPN or PW71 (where parents' blood was unavailable). The fetal and placental morphology on these cases was reviewed. The phenotype of the fetuses with non-mosaic triploidy was assessed in relation to the two types described by McFadden and Kalousek. Of the diandric fetuses three of the six showed mild-to-moderate symmetrical growth retardation and the other three had growth characteristics in accordance with their gestational ages. This study would suggest the fetal triploid 'Type 1' definition be modified to 'well grown to moderate symmetrical IUGR' to allow for such variation. In the digynic fetuses (McFadden/Kalousek Type 2) there were poor growth characteristics with IUGR being more severe and asymmetrical. The diandric fetuses were as common as digynic fetuses in this series. The ratio of diandric to digynic specimens was 11:8 but if only fetal specimens (not embryos or mosaic children) were included the ratio was 6:5. Many diandric conceptions end as partial moles but later in gestation diandric fetuses may be well grown. It is proposed that there may be a survival barrier for diandric fetuses early in gestation (possibly based on the proportion of vascularised placental villi), although once this is passed the diandric fetuses are comparatively more viable and better grown than digynic fetuses. In the XXY triploid fetuses, 5/6 had hypoplastic or ambiguous external genitalia (two were recorded as of female phenotype) as has been reported previously. In these, the gonadal histology was testicular in all the diandrics but in the single digynic XXY case, sex reversal was complete with normal uterus and Fallopian tubes and the gonads were histologically ovaries. Two triploid/diploid mosaics were proven to be due to digyny. The probable cause is delayed incorporation of the second polar body into a blastomere and there was evidence of identical alleles from the same sperm being present in both diploid and triploid cells. In one of these triploid/diploid mosaics in which there was a termination of pregnancy (TOP) after prenatal karyotyping the diploid cell line had trisomy 16 which was not evident in the triploid line. This trisomy was probably of post-zygotic origin and we suggest the fetus was rescued by the prominence of the triploid line.

Abortion, Spontaneous↗

Measurement of homonuclear proton couplings from regular 2D COSY spectra.

An interactive computer procedure is described which determines (1)H--(1)H couplings from fitting the cross-peak multiplets in regular phase-sensitive COSY spectra. The robustness and simplicity of the method rely on the fact that a given cross-peak intensity is not an independent variable in the fitting procedure, making it possible to measure couplings accurately even from individual cross peaks with unresolved multiplet structure.

Computer Graphics↗

Measurement of homonuclear proton couplings based on cross-peak nulling in CT-COSY.

A method in which 1H-1H scalar and dipolar couplings are obtained from the cross-peak nulling condition in a series of constant-time (CT) COSY spectra, as a function of the duration of the CT period, is described. The method is best suited for measurement of 1H-1H couplings in the range 5-20 Hz. It is shown, however, that results can be sensitive to cross-correlated relaxation effects. Also, artifactual resonances, resulting from strong coupling, can be quite pronounced in CT-COSY spectra, even when /J(AB)/(deltaA-deltaB)/<0.1. The experiments are demonstrated for the DNA dodecamer d(CGCGAATTCGCG)2, both in isotropic solution and in a liquid crystalline phase.

Computer Graphics↗

Successful treatment of primary and disseminated human lung cancers by systemic delivery of tumor suppressor genes using an improved liposome vector.

Delivery of therapeutic genes to disseminated tumor sites has been a major challenge in the field of cancer gene therapy due to lack of an efficient vector delivery system. Among the various vectors currently available, liposomes have shown promise for the systemic delivery of genes to distant sites with minimal toxicity. In this report, we describe an improved extruded DOTAP:cholesterol (DOTAP:Chol) cationic liposome that efficiently delivers therapeutic tumor suppressor genes p53 and FHIT, which are frequently altered in lung cancer, to localized human primary lung cancers and to experimental disseminated metastases. Transgene expression was observed in 25% of tumor cells per tumor in primary tumors and 10% in disseminated tumors. When treated with DOTAP:Chol-p53 and -FHIT complex, significant suppression was observed in both primary (P < 0.02) and metastatic lung tumor growth (P < 0.007). Furthermore, repeated multiple treatments revealed a 2.5-fold increase in gene expression and increased therapeutic efficacy compared to single treatment. Finally, animal survival experiments revealed prolonged survival (median survival time: 76 days, P < 0.001 for H1299; and 96 days, P = 0.04 for A549) when treated with liposome-p53 DNA complex. Our findings may be of importance in the development of treatments for primary and disseminated human lung cancers.

Acid Anhydride Hydrolases↗

Gene therapy of HSV-TK transferred by the EBV based expression vector on experimental hepatocellular carcinoma.

To study the therapeutic effects of herpes simplex virus thymidine kinase (HSV-TK) gene transferred by the EBV-based expression vector (pDR2) on experimental hepatocellular carcinoma, pDR2-TK gene was delivered into human hepatocellular carcinoma cell line SMMC-7721 by using liposome-mediated transfection technique, and then gene expression was detected by RT-PCR, and the killing effects were examined through MTT method. In the nude mice hepatoma model, the antitumor effects of pDR2-TK/GCV system was evaluated in terms of tumor growth. MTT results showed that the pDR2-TK/GCV had cytotoxic effect and about 70% SMMC-7721 cells were killed when GCV was at 1000 mumol/L. In vivo experiment showed that the tumor size in nude mice with transferred pDR2-TK gene was significantly smaller than that in control group (P < 0.01). On the 10th day the tumor in 3 mice (60%) disappeared completely after GCV treatment. It is concluded that the pDR2-TK/GCV system has marked killing effects on the experimental hepatocellular carcinoma.

Animals↗

Compositional analysis of human acquired enamel pellicle by mass spectrometry.

Relatively little is known about the formation of the acquired enamel pellicle other than that it involves the selective adsorption of specific proteins from oral fluids. Previous studies on the identification of pellicle components have relied largely on immunological or enzymatic detection and have been hampered by the fact that only minute quantities of pellicle can be removed from tooth surfaces. The present work describes an improved method of harvesting pellicle that combines mechanical and chemical removal; this approach was used to investigate systematically the desorption of in vitro pellicle components with different solutions. Eleven major in vitro pellicle proteins were identified by using a combination of electrophoretic separation and matrix-assisted laser desorption/ionization-reflectron time-of-flight mass spectrometry. A similar analysis of in vivo-formed pellicle revealed the presence of intact statherin, lysozyme, albumin and amylase. Further analysis of in vivo pellicle by liquid chromatography-electrospray ionization mass spectrometry suggested the presence of numerous low molecular-weight fragments of precursor proteins. The protein composition of in vitro whole-salivary pellicle adsorbed to hydroxyapatite and that of in vivo enamel pellicle differed for proline, the result of a reduction in the content of acidic proline-rich proteins in the in vivo samples. Unique features of the oral environment such as enzymatic activities or mineral surface properties may account for these differences between in vivo and in vitro pellicle formation.

Adult↗

Modulated polarization microscopy: a promising new approach to visualizing cytoskeletal dynamics in living cells.

In an effort to visualize cytoskeletal filaments in living cells, we have developed modulated polarization microscopy. Modulated polarization microscopy visualizes cytoskeletal filaments based on their birefringence but differs from the standard polarization microscopy by exploiting the angle dependence of birefringence. A prototype instrument has been developed using two Faraday rotators under computer control to change the angle of plane polarized light at a known rate. By placing one Faraday rotator before and one after the specimen, rotation produced by the first Faraday rotator is cancelled by the second. This allows the use of fixed polarizer and analyzer in a crossed configuration and continuous imaging of the specimen between crossed polarizers. The variation in polarization angle of light illuminating the specimen causes birefringent elements to oscillate in brightness. Images acquired as polarization angle is varied are then processed by a Fourier filter image-processing algorithm. The Fourier filtering algorithm isolates those signals that vary at the proper rate, whereas static or random signals are removed. Here we show that the modulated polarization microscope can reveal cytoskeletal elements including stress fibers and microtubules in living cells.

Animals↗

Re-evaluation of cellulose acetate polymer: angiographic findings and histological studies.

BACKGROUND: Cellulose acetate polymer (CAP) is a new liquid embolic material that has been used experimentally in intravascular treatment of intracranial aneurysms. But this compound is still controversial in some aspects such as safety, efficiency, and histological changes. In this study, we re-evaluated the material with regard to intravascular treatment of aneurysms. METHODS: The carotid arteries of rats and experimental aneurysms in canines were embolized with CAP. The effects of CAP were evaluated according to angiographic and histological results. RESULTS: A strong chemo-corrosive effect was observed. This led to severe damage to vessels and rupture of two thrombosed canine aneurysm models. There were significant technical difficulties including out-flow of CAP and a high rate of occlusion of the parent arteries. CONCLUSIONS: We conclude that currently CAP is not an ideal embolic material for intracranial aneurysms. Further tests and improvements are needed before it can be widely used clinically.

Angiography, Digital Subtraction↗

A facile approach to immobilize protein for biosensor: self-assembled supported bilayer lipid membranes on glassy carbon electrode.

A kind of solid substrate, glassy carbon (GC) electrode, was selected to support self-assembled lipid layer membranes. On the surface of GC electrode, we made layers of dimyristoylphosphatidylcholine (DMPG, a kind of lipid). From electrochemical impedance experiments, we demonstrated that the lipid layers on the GC electrode were bilayer lipid membranes. We immobilized horseradish peroxidase (HRP) into the supported bilayer lipid membranes (s-BLM) to develop a kind of mediator-free biosensor for H2O2. The biosensor exhibited fine electrochemical response, stability and reproducibility due to the presence of the s-BLM. As a model of biological membrane, s-BLM could supply a biological environment for enzyme and maintain its activity. So s-BLM is an ideal choice to immobilize enzyme for constructing the mediator-free biosensor based on GC electrode.

Biosensing Techniques↗

Findings and theoretical considerations on the usefulness of the acid-labile subunit in the monitoring of acromegaly.

Growth hormone (GH) action induces a variety of biochemical factors of which insulin-like growth factor I (IGF-I) is conventionally measured for the diagnosis and monitoring of GH-related disorders such as GH deficiency or acromegaly. IGF-I circulates predominantly as a ternary complex with IGF-binding protein 3 (IGFBP-3) and the acid labile subunit (ALS). In the treatment of active acromegaly with the GH receptor antagonist pegvisomant, ALS showed a closer correlation with the change in ring size, measured as a clinical indicator of disease activity, than did IGF-I or IGFBP-3. ALS thus seems to be a clinically useful marker of disease activity in acromegaly.

Acromegaly↗

Cytokine stimulation of energy expenditure through p38 MAP kinase activation of PPARgamma coactivator-1.

Cachexia is a chronic state of negative energy balance and muscle wasting that is a severe complication of cancer and chronic infection. While cytokines such as IL-1alpha, IL-1beta, and TNFalpha can mediate cachectic states, how these molecules affect energy expenditure is unknown. We show here that many cytokines activate the transcriptional PPAR gamma coactivator-1 (PGC-1) through phosphorylation by p38 kinase, resulting in stabilization and activation of PGC-1 protein. Cytokine or lipopolysaccharide (LPS)-induced activation of PGC-1 in cultured muscle cells or muscle in vivo causes increased respiration and expression of genes linked to mitochondrial uncoupling and energy expenditure. These data illustrate a direct thermogenic action of cytokines and p38 MAP kinase through the transcriptional coactivator PGC-1.

Animals↗

Different response of satellite cells in the kinetics of myogenic regulatory factors and ultrastructural pathology after Trichinella spiralis and T. pseudospiralis infection.

Infection of an intracellular parasitic nematode, Trichinella spiralis, resulted in severe damage in muscle cells which was followed by activation and proliferation of satellite cells. The repairing process, shortly after the damage, histopathologically resembled those seen after mechanical injury. Resemblance was also true for kinetics of expression of myogenic regulatory factors (MyoD, myogenin and MRF4). The difference resided in the next step where the muscle cell infected with T. spiralis transformed to a unique cell which is parasitologically known as the nurse cell, and the proliferated satellite cells did not differentiate to the muscle cell but to the nurse cell (misdifferentiation). Thus the nurse cell was a fusion of the transformed infected muscle cell and misdifferentiated satellite cells. Infection with another species of Trichinella, T. pseudospiralis, also caused cell damage, but more extensively involving the entire length of the infected muscle cells because no septum was formed to minimize the affected area. Therefore, a large number of satellite cells were activated and proliferated. The myogenic regulatory factors such as MyoD and myogenin were activated for a longer period than in the case with T. spiralis infection. The infected muscle cell transformed to the nurse cell, whose cytoplasm was characterized by extensive smooth endoplasmic reticulum. Satellite cells misdifferentiated to the nurse cell, whose cytoplasm was amorphous, void of distinct cell organelles. The two kinds of cytoplasm did not fuse as examined thus far. Thus infection with T. spiralis and T. pseudospiralis caused misdifferentiation of satellite cells, but in a different way.

Animals↗