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Biomedical subjects

Y Chen

Publications and source records attributed to Y Chen.

At least 19 recordsLinked to original sources
PubMed2024

Long-term exposure to particulate matter and all-cause and cause-specific mortality in an analysis of multiple Asian cohorts.

BACKGROUND: Exposure to ambient air pollution is associated with a significant number of deaths. Much of the evidence associating air pollution with adverse effects is from North American and Europe, partially due to incomplete data in other regions limiting location specific examinations. The aim of the current paper is to leverage satellite derived air quality data to examine the relationship between ambient particulate matter and all-cause and cause-specific mortality in Asia. METHODS: Six cohorts from the Asia Cohort Consortium provided residential information for participants, recruited between 1991 and 2008, across six countries (Bangladesh, India, Iran, Japan, South Korea, and Taiwan). Ambient particulate material (PM2·5) levels for the year of enrolment (or 1998 if enrolled earlier) were assigned utilizing satellite and sensor-based maps. Cox proportional models were used to examine the association between ambient air pollution and all-cause and cause-specific mortality (all cancer, lung cancer, cardiovascular and lung disease). Models were additionally adjusted for urbanicity (representing urban and built characteristics) and stratified by smoking status in secondary analyses. Country-specific findings were pooled via random-effects meta-analysis. FINDINGS: More than 300,000 participants across six cohorts were included, representing more than 4-million-person years. A positive relationship was observed between a 5 µg/m (Dockery et al., 1993) increase in PM2·5 and cardiovascular mortality (HR: 1·06, 95 % CI: 0.99, 1·13). The additional adjustment for urbanicity resulted in increased associations between PM2.5 and mortality outcomes, including all-cause mortality (1·04, 95 % CI: 0·97, 1·11). Results were generally similar regardless of whether one was a current, never, or ex-smoker. INTERPRETATION: Using satellite and remote sensing technology we showed that associations between PM2.5 and all-cause and cause-specific Hazard Ratios estimated are similar to those reported for U.S. and European cohorts. FUNDING: This project was supported by the Health Effects Institute. Grant number #4963-RFA/18-5. Specific funding support for individual cohorts is described in the Acknowledgements.

Humans↗
PubMed1992

Calcium and collagen binding properties of osteopontin, bone sialoprotein, and bone acidic glycoprotein-75 from bone.

Calcium binding properties of bone acidic glycoprotein-75, osteopontin, and bone sialoprotein were determined in 10 mM imidazole buffer (pH 6.8), containing either 60 mM KCl or 150 mM NaCl. Proteins assayed were first bound to nitrocellulose to mimic substrate-bound forms in vivo; retention of phosphoproteins was determined through use of radioiodinated tracers. Binding studies were carried out both as a function of calcium concentration and the amount of phosphoprotein. In the presence of 60 mM KCl, bone acidic glycoprotein-75 exhibited the largest calcium binding capacity (139 atoms/molecule at saturation), with bone sialoprotein intermediary (83 atoms/molecule) and osteopontin lowest (50 atoms/molecule). Sites detected for each phosphoprotein exhibited overall binding constants in the 0.5-1.0 mM extracellular range. In 150 mM NaCl and 1-2 mM total calcium, phosphoproteins bound between 72 and 19 mol of calcium/mol with the same relative order. Binding was proportional to amount of phosphoprotein in either salt condition. The presence of 5 mM calcium had a different effect on concentration-dependent binding to type I collagen for each phosphoprotein. Bone acidic glycoprotein-75 alone was found to undergo an unusual calcium-enhanced polymerization reaction, confirmed by light scattering measurements, wherein collagen binding was greatest with polymeric forms. These findings demonstrate that acidic phosphoproteins from bone bind calcium atoms with a range of capacities. Calcium appears to induce conformational changes in bone acidic glycoprotein-75 which influences its self-association and binding to different substrata.

Animals↗
PubMed1992

Incorporation of an EDTA-metal complex at a rationally selected site within a protein: application to EDTA-iron DNA affinity cleaving with catabolite gene activator protein (CAP) and Cro.

We have developed a simple procedure to incorporate an EDTA-metal complex at a rationally selected site within a full-length protein. Our procedure has two steps: In step 1, we use site-directed mutagenesis to introduce a unique solvent-accessible cysteine residue at the site of interest. In step 2, we derivatize the resulting protein with S-(2-pyridylthio)cysteaminyl-EDTA-metal, a novel aromatic disulfide derivative of EDTA-metal. We have used this procedure to incorporate an EDTA-iron complex at amino acid 2 of the helix-turn-helix motif of each of two helix-turn-helix motif sequence-specific DNA binding proteins, catabolite gene activator protein (CAP) and Cro, and we have analyzed EDTA-iron-mediated DNA affinity cleavage by the resulting protein derivatives. The CAP derivative cleaves DNA at base pair 2 of the DNA half-site in the protein-DNA complex, and the Cro derivative cleaves DNA at base pairs -3 to 5 of the DNA half-site in the protein-DNA complex. We infer that amino acid 2 of the helix-turn-helix motif of CAP is close to base pair 2 of the DNA half-site in the CAP-DNA complex in solution and that amino acid 2 of the helix-turn-helix motif of Cro is close to base pairs -3 to 5 of the DNA half-site in the Cro-DNA complex in solution.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Composition↗
PubMed1992

Retinoic acid is enriched in Hensen's node and is developmentally regulated in the early chicken embryo.

Retinoic acid (RA) has been considered as a potential morphogen in the chicken limb and has also been suggested to be involved in early embryonic development. On the basis of biological activity, previous reports suggest that Hensen's node, the anatomical equivalent in the chicken of the Spemann's organizer, may contain RA. Here, by using a molecular assay system, we demonstrate that Hensen's node contains retinoids in a concentration approximately 20 times more than that in the neighboring tissues. Furthermore, stage 6 Hensen's node contains approximately 3 times more retinoid than that of stage 4 embryos. These endogenous retinoids may establish a concentration gradient from Hensen's node to adjacent tissues and play a role in establishing the primary embryonic axis in the vertebrate. The results also suggest that the retinoid concentration in Hensen's node is developmentally regulated.

Animals↗
PubMed1992

Determination of the orientation of a DNA binding motif in a protein-DNA complex by photocrosslinking.

We have developed a straightforward biochemical method to determine the orientation of the DNA binding motif of a sequence-specific DNA binding protein relative to the DNA site in the protein-DNA complex. The method involves incorporation of a photoactivatable crosslinking agent at a single site within the DNA binding motif of the sequence-specific DNA binding protein, formation of the derivatized protein-DNA complex, UV-irradiation of the derivatized protein-DNA complex, and determination of the nucleotide(s) at which crosslinking occurs. We have applied the method to catabolite gene activator protein (CAP). We have constructed and analyzed two derivatives of CAP: one having a phenyl azide photoactivatable crosslinking agent at amino acid 2 of the helix-turn-helix motif of CAP, and one having a phenyl azide photoactivatable crosslinking agent at amino acid 10 of the helix-turn-helix motif of CAP. The results indicate that amino acid 2 of the helix-turn-helix motif is close to the top-strand nucleotides of base pairs 3 and 4 of the DNA half site in the CAP-DNA complex, and that amino acid 10 of the helix-turn-helix motif is close to the bottom-strand nucleotide of base pair 10 of the DNA half site in the CAP-DNA complex. The results define unambiguously the orientation of the helix-turn-helix motif relative to the DNA half site in the CAP-DNA complex. Comparison of the results to the crystallographic structure of the CAP-DNA complex [Schultz, S., Shields, S. & Steitz, T. (1991) Science 253, 1001-1007] indicates that the method provides accurate, high-resolution proximity and orientation information.

Amino Acid Sequence↗
PubMed1992

CDC46/MCM5, a yeast protein whose subcellular localization is cell cycle-regulated, is involved in DNA replication at autonomously replicating sequences.

Saccharomyces cerevisiae cells containing mutations in the cell-division-cycle gene CDC46 arrest with a large bud and a single nucleus with unreplicated DNA at the non-permissive temperature. This G1/S arrest, together with the increased rates of mitotic chromosome loss and recombination phenotype, suggests that these mutants are defective in DNA replication. The subcellular localization of the CDC46 protein changes with the cell cycle; it is nuclear between the end of M phase and the G1/S transition but is cytoplasmic in other phases of the cell cycle. Here we show that CDC46 is identical to MCM5, based on complementation analysis of the mcm5-1 and cdc46-1 alleles, complementation of the minichromosome maintenance defect of mcm5-1 by CDC46, and the genetic linkage of these two genes. Like mcm5-1, cdc46-1 and cdc46-5 also show a minichromosome maintenance defect thought to be associated with DNA replication initiation at autonomously replicating sequences. Taken together, these observations suggest that CDC46/MCM5 acts during a very narrow window at the G1/S transition or the beginning of S phase by virtue of its nuclear localization to effect the initiation of DNA replication at autonomously replicating sequences.

Amino Acid Sequence↗
PubMed1992

Secondary and tertiary structures involving chondroitin and chondroitin sulphates in solution, investigated by rotary shadowing/electron microscopy and computer simulation.

Rotary shadowing/electron microscopy of chondroitin 6-sulphate (CS6) and 4-sulphate (CS4) showed that the former, but not the latter, aggregated to mesh works. Preparations made from salt (ammonium acetate) solutions showed enhanced aggregation. Computer modelling, using molecular mechanics and dynamics, was applied to secondary structures (twofold helices) derived from NMR studies, to determine geometric and energetic constraints on duplex and higher-aggregate formation. The calculations suggested that chondroitin, CS6 and undersulphated CS4 could form duplexes, while CS4 could not, thus bridging the gap between atomic dimensions (NMR) and high polymer scale (electron microscopy). Calculations suggested that water structure helped to stabilise the twofold helix. It is proposed that the twofold helical, flat, tape-like molecules aggregate via hydrophobic bonding between the very extensive hydrophobic patches (9 CH units) repeated on alternating sides of the polymers. The negative charge of the polyanions opposes aggregate formation. Calculations showed that duplexes were formed with decreasing stability as the charge density increased, and as the charge was concentrated towards the centre line of the polymer (i.e. in CS4). The unsulphated polymer chondroitin could form duplexes and higher aggregates as readily as hyaluronan. Hyaluronan was calculated to form stable heteroduplexes with CS6 and CS4. The frequency and positioning of the sulphate-ester group within the polymer thus determines whether the molecule participates in duplex formation.

Animals↗
PubMed1992

Nerve growth factor promotes collateral sprouting of cholinergic fibers in the septohippocampal cholinergic system of aged rats with fimbria transection.

Nerve growth factor (NGF) was injected intraventricularly into aged (24 months) rats with unilateral fimbria transection. Controls received intraventricular injections of cytochrome c. A quantitative analysis of acetylcholinesterase (AChE)-positive fibers was used to evaluate whether the NGF treatment can stimulate regeneration and reinnervation of the cholinergic axons in the septohippocampal system of aged rats with fimbria transection. A marked increase in the density of AChE-positive fibers was observed in the lateral septum, the dorsal fornix and the dorsal hippocampus of the NGF-treated animals, as compared to the controls. In the lateral septum, the increase was observed in the 2-month NGF-treated animals but not in the 15-day NGF-treated animals. In the dorsal fornix at the level of the dorsal hippocampus, the increase was observed on both the lesioned and unlesioned sides of both the 15-day and 2-month NGF-treated animals. In the denervated (lesioned side) hippocampus, the increase took place in the dorsal hippocampus but not in the ventral hippocampus of both the 15-day and 2-month NGF-treated animals. There was no recovery of AChE-positive fibers on the lesioned side of the fimbria distal to the lesion site even in the 2-month NGF-treated animals. These results demonstrate that intraventricular injections of NGF can stimulate collateral sprouting of intact cholinergic axons in the septohippocampal system and promote cholinergic reinnervation of the denervated hippocampus of aged rats with fimbria transection.

Acetylcholinesterase↗
PubMed1992

The effect of methylation outside the recognition sequence of restriction endonuclease PvuII on its cleavage efficiency.

This study is to extend our earlier observation that Dam and Dcm methylation outside the PvuII recognition sequence inhibited PvuII cleavage in one of the three PvuII sites of pGEM4Z-ras DNA. In this paper, a new recombinant plasmid DNA, pGEM4-SV40ori-anti-ras, was constructed which has only two PvuII sites, I and II. The Dam and Dcm-methylated and unmethylated DNAs were produced in Escherichia coli and linearized by ScaI. The DNA molecules were digested with different amounts of PvuII. The results show that by comparing the DNA fragment number and intensity of the partial and final products in agarose gel, PvuII site I on the methylated DNA molecule was digested four- to eight-fold more slowly than site II. In the unmethylated plasmid DNA, the two PvuII sites were cleaved at about the same rate. The difference was caused only by methylation of Dam and Dcm sites outside the PvuII recognition sequence. A methylated Dam site immediately adjacent to the less efficiently cut PvuII site I may be responsible for the inhibitory effect. We suggest that a new parameter, involving methylation of sites outside the recognition sequence, be considered in kinetic experiments on cleavage.

Base Sequence↗
PubMed1992

Expression of the retinoblastoma gene product in bladder carcinoma cells associates with a low frequency of tumor formation.

Upon inactivation of both alleles of the retinoblastoma gene (RB), individuals develop the intraocular eye tumor, retinoblastoma. The gene encodes a Mr 110,000 phosphorylated nuclear protein that may be involved in regulation of the cell cycle. Besides retinoblastoma, mutations of the gene have been detected in several other types of tumors, including bladder carcinoma. Up to one-third of bladder carcinomas may contain mutations of the RB gene. Introducing the retinoblastoma gene into single retinoblastoma, osteosarcoma, or prostate carcinoma cell lines suppresses their tumorigenicity as assayed in nude mice. We have sought to extend these results by introducing the retinoblastoma gene into multiple bladder carcinoma lines, and analyzing several of the resulting, cloned lines. We have found that inhibition of tumorigenicity, as assayed by tumor growth in nude mice or growth of cells in soft agar, is the only consistent phenotype observed upon re-expression of RB in all bladder carcinoma cells examined. The effect of RB expression on growth and cellular morphology varied depending on the particular parental cell line. We conclude that RB expression generally correlates with reduced tumorigenicity, but not reduced growth rate, in bladder carcinoma cells.

Alleles↗
PubMed1992

Identification of a major growth factor for AIDS-Kaposi's sarcoma cells as oncostatin M.

Conditioned medium from human T cell leukemia virus type 2 (HTLV-II)-infected T cells supports the growth and long-term culture of cells derived from acquired immunodeficiency syndrome (AIDS)-associated Kaposi's sarcoma lesions (AIDS-KS cells). A protein of 30 kilodaltons was purified from conditioned medium that supports the growth of AIDS-KS cells. The amino-terminal sequence of this protein was identical to the amino-terminal sequence of Oncostatin M, a glycoprotein that inhibits the growth of a variety of cancer cells. Oncostatin M from conditioned medium stimulated a twofold increase in the growth of AIDS-KS cells at a concentration of less than 1 nanogram of the protein per milliliter of medium.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Solubilization and molecular characterization of active galanin receptors from rat brain.

Galanin receptors were solubilized from rat brain using the zwitterionic detergent 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonic acid (CHAPS). Binding of 125I-galanin to the soluble fraction was time- and temperature-dependent, saturable, and reversible. Scatchard analysis of binding data indicated that the soluble extract contained a single class of galanin binding sites with a Kd of 0.8 nM and a Bmax of 26 fmol/mg of protein. Unlabeled galanin and its fragments galanin(2-29) and galanin(1-15) antagonized the binding of 125I-galanin to CHAPS-solubilized extracts with relative potencies similar to those observed with membrane receptors. Galanin(3-29) was found inactive. Binding of 125I-galanin to CHAPS extracts was inhibited by guanine nucleotides with the following rank order of potency: GMP-P-(NH)P greater than GTP greater than GDP. Molecular analysis of the soluble galanin receptor by covalent cross-linking of 125I-galanin to CHAPS extracts using disuccinimidyl tartrate and further identification on SDS-PAGE indicated that the soluble galanin binding site behaves as a protein of Mr 54,000. After incubation of CHAPS extracts with 125I-galanin, gel filtration on Sephacryl S-300 followed by ultracentrifugation on sucrose density gradient revealed a binding component with the following hydrodynamic parameters: Stokes radius, 5 nm; s20,w, 4.5 S; Mr, 98,000; frictional ratio, 1.6. GMP-P(NH)P treatment of CHAPS extracts gave rise to a molecular form with the following characteristics: Stokes radius, 4 nm; s20,w, 3.3 S; Mr, 57,000; frictional ratio, 1.4.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

High-performance liquid chromatographic method for the simultaneous determination of monoethylglycinexylidide and lignocaine.

An accurate and sensitive high-performance liquid chromatographic method with UV detection was developed for the simultaneous measurement of monoethylglycinexylidide (MEGX) and lignocaine in human plasma and serum, using organic solvent extraction and trimethoprim (TMP) as an internal standard. The mean recoveries for MEGX, TMP and lignocaine were 86.1 +/- 3.7, 98.3 +/- 1.8 and 77.0 +/- 4.7%, respectively (n = 6). The relative standard deviations for MEGX concentrations of 10 and 200 ng/ml were less than 4% and for lignocaine concentrations of 200 and 1200 ng/ml they were less than 8%.

Chromatography, High Pressure Liquid↗
PubMed1992

Comparison of Hensen's node and retinoic acid in secondary axis induction in the early chick embryo.

Retinoic acid (RA) and Hensen's node, the organizer center in the chick embryo, have been shown to have polarizing activity when applied or grafted into the chick limb bud. Here we investigate and compare the effects of RA and grafted Hensen's node on the early chick embryo. Anion exchange beads soaked with RA at concentrations ranging from 5 to 100 ng/ml and implanted on the anterior side or on the left side of the host anteroposterior axis of a stage 4 chick embryo in ovo have the ability to induce secondary axis formation, while beads soaked with RA of the same concentration and implanted on the right side or on the posterior side of the host axis are unable to induce the secondary axis. All of the induced axes contain trunk-tail structures. Hensen's node from quail embryos implanted into the early chick blastoderm could also cause the formation of secondary axes in addition to self-differentiation of the graft into a secondary axis. Both RA and grafted Hensen's node caused the inhibition of forebrain development with an increase in hindbrain development and the host heart to loop in an abnormal direction. The results support the hypothesis that Hensen's node is a source of RA which is involved in early embryogenesis. Alternatively, RA might stimulate the formation of Hensen's nodal properties in adjacent tissue.

Animals↗
PubMed1992

In vivo phosphorus NMR spectroscopy of skin using a crossover surface coil.

A modified crossover surface coil with minimal B1 field penetration was used for collection of skin phosphorus NMR spectra. Projection imaging experiments show that the coil-sensitive volume is uniform at the phosphorus frequency, but strikingly nonuniform at the proton frequency. Experiments with an in vitro phosphorus phantom, designed to simulate skin and underlying tissue, demonstrated that 45.1% (+/- 1.2%) of total signal was derived from Sprague-Dawley rat skin and 19.3% (+/- 1.4%) of total signal was derived from Fischer-344 rat skin. 31P MR spectra of rat skin in vivo permitted resolution of four phosphorus compounds: nucleoside triphosphates, phosphocreatine (PCr), inorganic phosphate (Pi), and phosphomonoester. Spectra collected after skin flap surgery in Fischer-344 rats showed a 50.1% (+/- 7.6%) reduction in the ratio of PCr/Pi within 30 min of surgery, compared to presurgical PCr/Pi levels (P less than 0.01). Skin phosphorus spectra are potentially useful for assessment of skin flap and skin graft viability.

Animals↗
PubMed1992

Time trend and age-period-cohort effects on incidence of esophageal cancer in Connecticut, 1935-89.

The purpose of this study was to examine the incidence pattern of esophageal cancer in Connecticut (USA) during the past decades, and to identify components of birth cohort, period, and and age as determinants of the observed time trends by regression modelling. This study is based on all of the esophageal cancer cases reported to the Connecticut Tumor Registry between 1935 and 1989. A total of 6,310 incident cases were included. Results indicate that among males, the overall age-adjusted incidence rate of esophageal cancer increased after 1935 and peaked between 1955 and 1959. Since then, incidence rates have been relatively stable. Among females, the overall esophageal cancer rate has not changed markedly since 1935. Analysis by histologic type indicates that the incidence rate of squamous cell carcinoma has been declining in this population; adenocarcinoma, however, showed a continuous increase. A fivefold increase among males and a threefold increase among females were observed for adenocarcinoma of the esophagus between 1970 and 1989. If cancers of the esophagus and gastric cardia are considered together, the incidence rate of adenocarcinoma exceeds that of squamous cell carcinoma among males during 1985-89. The observed increasing trend for adenocarcinoma of the esophagus is mainly from cancers arising in the lower third of the esophagus and primarily among Whites, especially White males. The results from regression modeling indicate that both period and birth cohort may have contributed to the observed increasing trend, and adenocarcinoma of the esophagus is likely to increase continuously in this population in the coming years.

Adenocarcinoma↗
PubMed1992

Analysis of prognostic factors affecting renal allograft survival.

A total of 201 consecutive cadaveric kidney transplantations were performed in 188 patients at the Chinese Great Wall Hospital, Beijing, from October 1977 to May 1990. The overall 1-, 2-, 5-, and 10-year graft survival rates were 75.5%, 64.5%, 37.0%, and 32.9%, respectively. In the last 5 years, these figures have risen to 83.7% at 1 year, 69.5% at 2 years, and 40.8% at 5 years, respectively. The 14 variables correlating to graft survival in the present study were analyzed using the log rank test for univariate analysis and the Cox proportional hazard model for multivariate analysis. The results show that immunosuppressive drug therapy, cold ischemia time, acute tubular necrosis, and infection were significant factors affecting the survival of cadaveric kidney grafts. Triple therapy with low-dose cyclosporin, as compared to conventional immunosuppressive drug therapy, significantly increased the 1-year graft survival rate (90.3% vs 31.3%) but did not influence the long-term graft survival rate after 3 years. The incidence of acute tubular necrosis significantly correlated to the cold ischemia time and influenced the 1-year graft survival. Analysis showed that the lymphocytotoxic crossmatch affected graft survival after 3 years and that most late graft losses were due to chronic rejection, suggesting that histocompatibility is the strongest factor affecting long-term graft survival. A beneficial effect of pretransplant blood transfusions on long-term graft survival was seen in patients treated with conventional immunosuppressive drugs but not in cyclosporin-treated patients.

Adult↗