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Biomedical subjects

S Yu

Publications and source records attributed to S Yu.

At least 37 records · Page 2Linked to original sources

Human peroxisome proliferator-activated receptor alpha (PPARalpha) supports the induction of peroxisome proliferation in PPARalpha-deficient mouse liver.

Peroxisome proliferators, which function as peroxisome proliferator-activated receptor alpha (PPARalpha) agonists, induce peroxisomal, microsomal, and mitochondrial fatty acid oxidation enzymes, in conjunction with peroxisome proliferation, in liver cells. Sustained activation of PPARalpha leads to the development of liver tumors in rats and mice. The assertion that synthetic PPARalpha ligands pose negligible carcinogenic risk to humans is attributable, in part, to the failure to observe peroxisome proliferation in human hepatocytes. To explore the mechanism(s) of species-specific differences in response to PPARalpha ligands, we determined the functional competency of human PPARalpha in vivo and compared its potency with that of mouse PPARalpha. Recombinant adenovirus that expresses human or mouse PPARalpha was produced and administered intravenously to PPARalpha-deficient mice. Human as well as mouse PPARalpha fully restored the development of peroxisome proliferator-induced immediate pleiotropic responses, including peroxisome proliferation and enhanced expression of genes involved in lipid metabolism as well as nonperoxisomal genes, such as CD36, Ly-6D, Rbp7, monoglyceride lipase, pyruvate dehydrogenase kinase-4, and C3f, that have been identified recently to be up-regulated in livers with peroxisome proliferation. These studies establish that human PPARalpha is functionally competent and is equally as dose-sensitive as mouse PPARalpha in inducing peroxisome proliferation within the context of mouse liver environment and that it can heterodimerize with mouse retinoid X receptor, and this human PPARalpha-mouse retinoid X receptor chimeric heterodimer transcriptionally activates mouse PPARalpha target genes in a manner qualitatively similar to that of mouse PPARalpha.

Animals↗

'In vivo perfusion Turnbull's reaction' for Fe(II) histochemistry in non-anoxic/non-ischemic and anoxic/ischemic cat brains.

We developed a simple but ingenious histochemical method, 'in vivo perfusion-Turnbull's reaction', for the visualization of non-heme Fe(II) of the brain; in situ release of Fe(2+) ions was coupled with formation of insoluble reaction product (Turnbull's blue) by in vivo perfusion of acid ferricyanide through the abdominal (non-anoxic/non-ischemic brain) or ascending (anoxic/ischemic brain) aorta in the deeply anesthetized adult cats. Frozen sections of the brain were treated according to the method of Nyguen-Legros et al. [12] to intensify Turnbull's reaction. The method revealed that cytoplasmic Fe(III) was reduced to Fe(II) in oligodendroglias in anoxic/ischemic (for 20 min) brains, and that Fe(II) was concentrated in the neuronal and glial cell nuclei regardless of the presence or absence of blood supply impairment.

Animals↗

The mapping of nucleosomes and regulatory protein binding sites at the Saccharomyces cerevisiae MFA2 gene: a high resolution approach.

We have developed an end-labelling approach to map the positions of nucleosomes and protein binding sites at nucleotide resolution by footprinting micrococcal nuclease (MNase)-sensitive sites. Using this approach we determined that the MFA2 gene and its upstream control regions have four positioned nucleosomes when transcription is repressed in mating type alpha cells and that the nucleosomes lose their positioning when the gene became transcriptionally active in mating type a cells. We also detected MNase-hypersensitive sites in the alpha2 operator region of MFA2 in alpha cells but not in a cells. These probably result from the change in the local DNA conformation due to protein(s) binding in this region that governs MFA2 transcription.

Base Sequence↗

Efficient asymmetric synthesis of biologically important tryptophan analogues via a palladium-mediated heteroannulation reaction.

A novel and concise synthesis of optically active tryptophan derivatives was developed via a palladium-catalyzed heteroannulation reaction of substituted o-iodoanilines with an internal alkyne. The required internal alkyne 14a or 25 was prepared in greater than 96% de via alkylation of the Schöllkopf chiral auxiliary 19 employing diphenyl phosphate as the leaving group. The Schöllkopf chiral auxiliary was chosen here for the preparation of L-tryptophans would be available from D-valine while the D-isomers required for natural product total synthesis would originate from the inexpensive L-valine (300-g scale). Applications of the palladium-catalyzed heteroannulation reaction were extended to the first asymmetric synthesis of L-isotryptophan 38 and L-benz[f]tryptophan 39. More importantly, the optically pure 6-methoxy-D-tryptophan 62 was prepared by this protocol on a large scale (>300 g). This should permit entry into many ring-A oxygenated indole alkaloids when coupled with the asymmetric Pictet-Spengler reaction. In addition, an improved total synthesis of tryprostatin A (9a) was accomplished in 43% overall yield employing this palladium-mediated process.

Alkylation↗

Pharmacokinetic study of intralesional cisplatin for the treatment of hepatocellular carcinoma.

BACKGROUND: In the current study the authors examined the pharmacokinetics of direct intralesional injection of cisplatin/epinephrine/bovine collagen gel in patients with hepatocellular carcinoma and cirrhosis. METHODS: Six patients with cirrhosis and unresectable hepatocellular carcinoma received a direct intralesional injection (range, 6.7-26.7 mg) into their tumors under ultrasonographic guidance. The authors determined the total cisplatin (Pt) concentration in the plasma and urine and nonprotein-bound free Pt in plasma ultrafiltrate using flameless atomic absorption spectrometry. Data from individual patients were analyzed to calculate the pharmacokinetic parameters via a noncompartmental method for constant infusion. To demonstrate that the changes in pharmacokinetics are not related to the underlying cirrhosis, a similar methodology was applied to measure the pharmacokinetic parameters of four similar patients who were treated with cisplatin, 75 mg/m(2), as a 1-hour intravenous infusion. RESULTS: The time to attain maximum concentration of total Pt after intralesional injection was dose-dependent and ranged from 2-13 hours. The concentration-time curve was biphasic in nature. The initial half-life of total Pt in patients who received an intralesional injection varied with the cisplatin dose. The initial half-life for cisplatin doses < 15 mg was approximately 9 hours and the initial half-life at higher cisplatin doses (> 15 mg) was approximately 25 hours. The area under the curve (AUC) was dose-dependent with values ranging from 38-150 microm/mL x hour. Pharmacokinetic parameters for free Pt (ultrafiltrate) were significantly different. The time to attain maximum concentration (t-max) and terminal half-life were shorter and the average AUC was approximately 100-fold lower than total Pt. After the intravenous infusion of cisplatin, the t-max for total and free Pt was 1.3 hours and 1.1 hours, respectively. The terminal half-life and average AUC for total Pt was 194 hours and 247 microg/mL per hour, respectively, and its corresponding parameters for free Pt after intravenous infusion were much lower, similar to the findings for the intralesional injection. CONCLUSIONS: The prolonged t-max and initial half-life noted with the intralesional injection of cisplatin/epinephrine/collagen gel are consistent with its proclaimed ability to retain cisplatin at the tumor and delay its release in systemic circulation. The kinetics of intralesional cisplatin injection also suggest local sequestration of the drug in the injected site. Parameters of intravenous cisplatin infusion in cirrhotic patients are similar to those of patients from the historic control group.

Aged↗

Beam propagation of x rays in a laser-produced plasma and a modified relation of interferometry in measuring the electron density.

In this paper, using a quantum mechanical technique and introducing the so-called V representation (where the representation transformation is made by using the potential Hamiltonian V), we studied x-ray propagation in a linear plasma medium both analytically and numerically. A modified relation between the phase of the probe and the reference light and the electron density of the plasma is derived, in which the contribution of the gradient of the electron density has been taken into account. It is shown that this relation has the advantage in measurements of the electron density of a plasma using the x-ray interferometry technique of lessening the errors originating from the electron density gradient. The validity of x-ray interferometry is discussed in both mathematical and physical terms.

Journal Article↗

Reaction-controlled phase-transfer catalysis for propylene epoxidation to propylene oxide.

The epoxidation of olefins with H2O2 was performed with a tungsten-containing catalyst. This insoluble catalyst forms soluble active species by the action of H2O2, and when the H2O2 is used up, the catalyst precipitates for easy recycling. Thus, the advantages of both homogeneous and heterogeneous catalysts are combined in one system through reaction-controlled phase transfer of the catalyst. When coupled with the 2-ethylanthraquinone/2-ethylanthrahydroquinone redox process for H2O2 production, O2 can be used for the epoxidation of propylene to propylene oxide with 85% yield based on 2-ethylanthrahydroquinone without any co-products. This approach avoids the problematic co-products normally associated with the industrial production of propylene oxide.

Journal Article↗

[Diagnosis and treatment of brain tumors in jugular foramen region].

OBJECTIVE: To analyze the diagnosis and treatment of brain tumors in jugular foramen region. METHODS: 22 patients with brain tumor in jugular foramen region who had been diagnosed and treated from 1996 to 2000. Considerable literature was reviewed. RESULTS: Tumor imaging technique showed masses of different shapes in unilateral jugular foramen region. All of the 22 patients underwent operation via different approaches. Total removal of the tumor was achieved in 20 patients and subtotal removal in 2. Pathological examination confirmed the diagnosis of neurinoma in 13 patients, tumor of glomus jugulare in 4, meningioma in 3, chordoma in 1, and metastatic tumor in 1. Only one patient died after operation. The mortality rate was as low as 4.5%. CONCLUSION: The most common tumors in jugular foramen region are neurinoma, tumor of glomus jugulare, and meningioma. Surgery is effective in treatment of brain tumor in jugular foramen region.

Adolescent↗

RAD9, RAD24, RAD16 and RAD26 are required for the inducible nucleotide excision repair of UV-induced cyclobutane pyrimidine dimers from the transcribed and non-transcribed regions of the Saccharomyces cerevisiae MFA2 gene.

In this study, the effect of a prior UV irradiation on the removal of cyclobutane pyrimidine dimers (CPDs) from the transcribed strand (TS) and non-transcribed strand (NTS) of the MFA2 gene in haploid Saccharomyces cerevisiae (S. cerevisiae) cells was investigated. In NER competent cells, the pre-irradiation with a dose of 20J/m2 enhances the removal of CPDs induced by a second UV dose of 100J/m2 in the TS and the NTS of MFA2 gene except for the CPDs in the region +258 to +298 in the NTS, where the enhanced repair was absent. No inducible repair was observed in rad9, rad24, rad16 and rad26 cells, indicating two checkpoint genes RAD9 and RAD24, the global repair gene RAD16 and the transcription coupled repair gene RAD26 are essential for inducible NER.

Cell Cycle Proteins↗

Increased insulin sensitivity in Gsalpha knockout mice.

The stimulatory guanine nucleotide-binding protein (G(s)) is required for hormone-stimulated cAMP generation. Gnas, the gene encoding the G(s) alpha-subunit, is imprinted, and targeted disruption of this gene in mice leads to distinct phenotypes in heterozygotes depending on whether the maternal (m-/+) or paternal (+/p-) allele is mutated. Notably, m-/+ mice become obese, whereas +/p- mice are thinner than normal. In this study we show that despite these opposite changes in energy metabolism, both m-/+ and +/p- mice have greater sensitivity to insulin, with low to normal fasting glucose levels, low fasting insulin levels, improved glucose tolerance, and exaggerated hypoglycemic response to administered insulin. The combination of increased insulin sensitivity with obesity in m-/+ mice is unusual, because obesity is typically associated with insulin resistance. In skeletal muscles isolated from both m-/+ and +/p- mice, the basal rate of 2-deoxyglucose uptake was normal, whereas the rate of 2-deoxyglucose uptake in response to maximal insulin stimulation was significantly increased. The similar changes in muscle sensitivity to insulin in m-/+ and +/p- mice may reflect the fact that muscle G(s)alpha expression is reduced by approximately 50% in both groups of mice. GLUT4 expression is unaffected in muscles from +/p- mice. Increased responsiveness to insulin is therefore the result of altered insulin signaling and/or GLUT4 translocation. This is the first direct demonstration in a genetically altered in vivo model that G(s)-coupled pathways negatively regulate insulin signaling.

Animals↗

Characterization of nuclear factors binding to AT-rich element in the rat p53 promoter.

In this study, we identified AT-rich element located at positions -504 to -516 in the rat p53 promoter by DNase I foot printing assay. This region was previously identified as a positive regulatory element in the murine p53 promoter and designated as PBF1 (p53 binding factor 1) binding site. However, the proteins binding to this AT-rich element have not been identified yet. Therefore, we characterized the binding protein by various biochemical methods. First, we confirmed that by the oligonucleotide competition assay, nuclear factors bound to the AT-rich element in a sequence-specific manner. Two binding proteins were identified in southwestern blotting analysis and the molecular masses of the proteins were 60 and 40 kDa, respectively. The proteins were stable to denaturants or ionic strength. Treatment of chelators showed that the binding proteins did not require divalent cation for DNA-binding activity. In addition, the binding proteins were labile to protease treatment. This study showed that 60 and 40 kDa proteins bound to AT-rich element and the physico-chemical properties provided new insights into the binding proteins.

Animals↗

Apoptosis induced by progesterone in human ovarian cancer cell line SNU-840.

Progesterone has been used as an ingredient of anticancer drug for patients with ovarian carcinoma. However, the mechanism of anticancer effects by progesterone has not been understood. In this study, the effects of progesterone on ovarian cancer cells, SNU-840, were investigated. After the incubation with progesterone, the viability of the cells was evaluated by MTT assay. As a result, 45% of the cells were viable after 48 h of incubation with 100 microM progesterone. In addition, [(3)H]thymidine incorporation assay showed that the proliferation of the cells was completely inhibited by progesterone after 48 h of incubation at 100 microM concentration. Colorimetric TUNEL assay revealed the fragmentation of the chromosomal DNA, suggesting that the process of the cell death was apoptosis. The level of the p53 mRNA was determined by northern blotting assay, since many apoptosis processes are mediated by up-regulation of the p53 expression. The level of the p53 mRNA reached its maximum at 12 h and decreased after 24 h of incubation with progesterone. In conclusion, progesterone inhibits the proliferation and elicits apoptosis of SNU-840 cells. Also, it up-regulates the p53 mRNA transiently.

Apoptosis↗

Characteristics of inflammatory cells in spontaneous autoimmune thyroiditis of NOD.H-2h4 mice.

Thyroid lesions develop in most NOD.H-2h4 mice 6 weeks after they are given 0.05% NaI in drinking water. B cells are required for spontaneous autoimmune thyroiditis (SAT) development, and anti-thyroglobulin autoantibody levels correlate with SAT severity. Immunohistochemical staining of thyroids obtained 2-10 weeks after administration of NaI water suggested that CD4+ T cells initially infiltrated the thryoid, followed by CD8+ T cells and B cells. Intrathyroidal CD4+ T cells are more numerous than CD8+ T cells. CD4+ T cells and B cells form aggregates in the thyroid, while CD8+ T cells are scattered throughout the thyroid. Intrathyroidal germinal centre-like structures could be observed in thyroid lesions with 2-3+ SAT and intrathyroidal B cells co-expressed OX40L. By RT-PCR, intrathyroidal expression of OX40L, OX40, CD40L, IL-2R, CTLA-4 and Igbeta mRNA correlated closely with the SAT severity score. These molecules were not expressed in normal thyroids. In the spleen, OX40L-positive cells were detected at 2 weeks and increased 4-6 weeks after NaI water. OX40, OX40L, CD40L, IL-2R and B7-1 as well as IFN-gamma and IL-4 mRNA were minimally expressed in normal spleens, usually began to be expressed at 2 weeks and increased to maximal level 4-8 weeks after NaI water. These results suggest that in NOD.H-2h4 mice, the OX40L, OX40, CD40L and B7 molecules, which increase in the spleen and thyroid of these mice after receiving NaI water, may play a role in SAT development, implying that one or more of these molecules might be good targets for the prevention or treatment of SAT.

Abatacept↗

Clinical study on the treatment of 325 cases of atrioventricular node reentrant tachycardia by radiofrequency catheter ablation.

In order to improve the efficacy of modified inferior method or middle method of radiofrequency catheter ablation (RFCA) in the treatment of atrioventricular node reentrant tachycardia (AVNRT), the clinical data of 325 cases of AVNRT from March 1992 to Feb. 2000 being subjected to the treatment of RFCA were retrospectively analyzed. The results showed that the successful rate was increased and recurrence was decreased year by year. In the recent 4 years the effective rate was up to 100%. The complication of three grade of AVB occurred in 3% and recurrent rate in 9.1% before March 1996, but both of them were zero in the last 3 years. The time of RFCA procedure and X-ray exposure was significantly reduced. It was concluded that ablating more than 3 targets by modified inferior method or middle method with energy titrating and strict endpoint was the crux of obtaining satisfactory therapeutic effects and preventing recurrence.

Adolescent↗

Sequence analysis shows that ribgrass mosaic virus Shanghai isolate (RMV-Sh) is closely related to Youcai mosaic virus.

The complete nucleotide sequence of an isolate of Ribgrass mosaic virus (RMV-Sh) from Brassica chinensis (Qingcai) in Shanghai, China was determined. The genome consisted of 6301 nucleotides and its genomic organization was similar to those of other crucifer-tobamoviruses. Comparisons of the nucleotide and predicted amino acid sequences and phylogenetic analyses showed that RMV-Sh had very high homology (> 95% identical nucleotides and 97.7-99.6% identical amino acids) to a sequence of Youcai mosaic virus (YMV = Chinese rape mosaic or Oilseed rape mosaic virus), despite differences in host range or symptoms and this strongly suggests that these isolates should be regarded as belonging to the same species. Only coat protein sequences have been reported for other RMV isolates but it seems likely that the distinction between RMV and YoMV will be difficult to maintain.

Base Sequence↗

Protein phosphatase 2A: identification in Oryza sativa of the gene encoding the regulatory A subunit.

A 2225 bp cDNA, designated RPA1, was isolated from an Oryza sativa cDNA library. Analysis revealed a 1761 bp coding sequence with 15 non-identical repeat units. The ORF encoded the A regulatory subunit of protein phosphatase 2A (PP2A-A) as ascertained by complementation of the yeast tpd3 mutant defective in this gene. The corresponding genomic DNA from a rice genome BAC library revealed that the gene contains eleven introns. The rice genome contains only a single copy of this gene as judged by Southern blot analysis. The PP2A protein is highly conserved in nature; the rice protein shows 88% amino acid identity with its counterparts in Arabidopsis or Nicotiana tabacum.

Amino Acid Sequence↗

The lowering effect of high copper intake on selenium retention in weanling rats depends on the selenium concentration of the diet.

The question addressed was whether the influence of dietary copper concentration on selenium metabolism depends on the amount of selenium in the diet. Weanling, male rats were fed purified diets containing either 1 (low), 4 (normal) or 42 (high) mg Cu/kg diet and either 0.03 (low), 0.05 (normal) or 1.0 (high) mg Se/kg diet in a 3(2) factorial design. Extra copper was added to the diets in the form of CuSO(4) x 5H(2)O and selenium as Na(2)SeO(3) x 5H(2)O. In rats fed either the low or normal amounts of selenium, higher intakes of copper decreased the apparent intestinal selenium absorption and increased urinary selenium excretion. The effects of copper on selenium absorption, excretion and retention were not seen in rats fed the high-selenium diets. An increase in dietary copper concentrations elevated selenium concentrations in the liver and kidneys, but slightly lowered those in the spleen of rats that were fed the diets with the normal level of selenium. In rats that were fed the diets with either low or high selenium concentration, copper intake had no effect on organ selenium concentrations. Glutathione peroxidase activity in erythrocytes was raised by feeding the diets which contained either normal or high copper content instead of those that were low in copper. It is concluded that the amount of selenium in the diet determines whether or not an increase in dietary copper concentration affects selenium metabolism.

Animals↗