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Y Zhao

Publications and source records attributed to Y Zhao.

At least 811 records · Page 45Linked to original sources
PubMed1996

Inotropic agent EMD-53998 weakens nucleotide and phosphate binding to cross bridges in porcine myocardium.

The effect of EMD-53998 (EMD) on elementary steps of the cross-bridge cycle in skinned porcine myocardium was studied to understand the positive inotropic mechanisms of EMD. The kinetic constants of the elementary steps were obtained by sinusoidal analysis and compared in the presence and absence of 50 microM EMD. In the presence of 50 microM EMD, the equilibrium constant of the cross-bridge detachment step decreases three times, and the equilibrium constant of the cross-bridge attachment (force generation) step increases two times. Our results further show that, in the presence of 50 microM EMD, the association constants of MgATP and MgADP decrease to one-ninth and one-third, respectively, and the association constant of phosphate decreases to one-third. These results indicate that EMD suppresses the nucleotide binding to cross bridges and increases cross-bridge resistance to phosphate accumulation in myocardium. These results predict that EMD decreases the number of detached cross bridges and increases the number of attached cross bridges. This prediction is consistent with the twofold increase of isometric tension with 50 microM EMD.

Adenosine Diphosphate↗
PubMed1996

Developmental changes in alpha 1-adrenergic receptors, IP3 responses, and NE-induced contraction in cerebral arteries.

Cerebral arteries show significant developmental and artery-specific changes in noradrenergic-mediated contraction. To test the hypothesis that these changes result from differences in the density of alpha 1-adrenergic receptors (alpha 1-ARs) and/or norepinephrine (NE)-induced inositol 1,4,5-trisphosphate [Ins(1,4,5)P3,IP3] synthesis, we quantified these variables and the NE-induced contraction in the common carotid artery (Com) and main branch cerebral arteries (MBC) from term fetal (approximately 140 gestational day) and newborn (2- to 5-day) sheep and compared them with adult values. In fetal and newborn Com, maximal contractions to NE (percent K+ maximum response) were 132 +/- 14 and 118 +/- 9%, respectively (adult = 92 +/- 7%). For fetal and newborn middle cerebral artery, these values were 34 +/- 10 and 43 +/- 7%, respectively (adult = 24 +/- 7%). alpha 1-AR density values in Com of fetal and newborn sheep were 113 +/- 18 and 106 +/- 4 fmol/mg protein, respectively (adult = 54 +/- 3 fmol/mg protein). For the MBC, density values were 47 +/- 2 and 24 +/- 3 fmol/mg protein, respectively (adult = 23 +/- 3 fmol/protein). In term fetal and newborn MBC, NE produced dose-dependent increases in Ins(1,4,5)P3, the maximal increases above basal values being 245 +/- 40 and 189 +/- 16%, respectively (adult = 254 +/- 35%). Neither fetus nor newborn Com showed significant Ins(1,4,5)P3 responses to NE. We concluded that in fetal and newborn Com and MBC, alpha 1-AR density and NE-induced Ins(1,4,5)P3 response varied as a function of developmental age and specific vessel. However, these variations did not correlate with NE-induced maximum contraction. Thus we reject the hypothesis that age-dependent and vessel-specific differences of cerebral artery adrenergic-mediated contraction are a function of alpha 1-AR density or Ins(1,4,5)P3 response. Rather, the differences would appear to result from other factors such as non-Ins(1,4,5)P3-mediated calcium activation and/or sensitivity to Ins(1,4,5)P3. The studies also suggest considerable potential for maturational modulation of pharmacomechanical coupling and homeostatic regulation of cerebrovascular tone.

Aging↗
PubMed1996

Hypoxia-induced pulmonary arterial contraction appears to be dependent on myosin light chain phosphorylation.

The signal transduction pathway of hypoxic pulmonary arterial contraction has not been elucidated. Phosphorylation of the 20-kDa myosin light chain (MLC20) is thought to be essential for vascular muscle contraction. However, there are reports that smooth muscle will contract in response to nonphysiological stimuli such as phorbol esters without the involvement of MLC20 phosphorylation. The purpose of this study was to determine if hypoxia-induced pulmonary arterial contraction is dependent on MLC20 phosphorylation. Isolated rat pulmonary and carotid (for comparative purposes) arterial strips were contracted with 80 mM KCl to establish maximum active tension in response to membrane depolarization. The strips were then stimulated with one of the following: 30 mM KCl, 1 microM phenylephrine, 0.01 microM angiotensin II, 1 microM phorbol 12-myristate 13-acetate (PMA), or hypoxia (95% N2-5% CO2). In some experiments ML-9, a myosin light chain kinase inhibitor, or calphostin C, a protein kinase C (PKC) inhibitor, was introduced into the bath before hypoxia. Isometric tension was recorded as a function of time. Muscle strips were freeze-clamped (liquid N2) at various time points during the course of responses to the various stimuli. MLC20 phosphorylation levels were measured by ureaglycerol gel electrophoresis followed by Western blot procedure. Results show that increased MLC20 phosphorylation correlates with initiation of pulmonary arterial smooth muscle contraction in response to all agonists with the exception of PMA, a known activator of PKC. The MLC20 phosphorylation levels correlate with tension development in response to hypoxia, and ML-9 abolished the hypoxic contractions. In contrast, hypoxia relaxed carotid arterial muscle, and there was a corresponding decrease in the MLC20 phosphorylation level. In conclusion, hypoxia appears to result in MLC20 phosphorylation-mediated contraction in conduit pulmonary arterial muscle and in MLC20 dephosphorylation-mediated relaxation in systemic arterial muscle.

Angiotensin II↗
PubMed1996

Estrogen biosynthesis proximal to a breast tumor is stimulated by PGE2 via cyclic AMP, leading to activation of promoter II of the CYP19 (aromatase) gene.

In the present report, we show that prostaglandin (PG) E2 is the most potent factor which stimulates aromatase expression via cyclic AMP and promoter II. PGE2 acts via EP1 and EP2 receptor subtypes to stimulate both the PKC and PKA pathways. The combined stimulation of both of these pathways results in maximal expression of promoter II-specific CYP19 transcripts. Since PGE2 is a major secretory product both of breast tumor epithelial cells and fibroblasts, as well as of macrophages infiltrating the tumor site, then this could be the mechanism whereby estrogen biosynthesis is stimulated in breast sites adjacent to a tumor, leading in turn to increased growth and development of the tumor itself.

Adipose Tissue↗
PubMed1996

Suppression of transforming growth factor-beta (TGF beta) and TGF beta receptor messenger ribonucleic acid and protein expression in leiomyomata in women receiving gonadotropin-releasing hormone agonist therapy.

The expression and cellular distribution of transforming growth factor-1 (TGF beta 1) through TGF beta 3 and TGF beta type I-III receptor messenger ribonucleic acid (mRNA) and protein were analyzed in leiomyomata from patients receiving GnRH agonist (GnRHa; leuprolide acetate) compared to those in untreated controls. Standard reverse transcription-PCR revealed that the unaffected myometrium and leiomyomata from leuprolide-treated and untreated patients express TGF beta 1-3 and TGF beta type I-III receptor mRNA. The myometrial and leiomyomata smooth muscle cells were the primary site of TGF beta 1-3 and TGF beta type I and II receptor mRNA and protein expression, as determined by in situ hybridization and immunohistochemical localization. These observations indicate that leiomyomata express a higher of level of TGF beta and TGF beta receptor mRNA and protein than unaffected myometrium during the secretory phase of the menstrual cycle, and women who received leuprolide acetate therapy had a substantially lower level of expression than untreated controls. Furthermore, competition-based quantitative reverse transcription-PCR using synthetic internal standards revealed that leiomyomata express a significantly higher number (copies per cell) of TGF beta type II receptor mRNA, followed by TGF beta 1, TGF beta type I receptor, TGF beta 2, and TGF beta 3 (P < 0.05). However, there was a significant decrease in the levels (copies per cell) of TGF beta 1, TGF beta 3, and TGF beta type I and type II receptor mRNA expression in leiomyomata from leuprolide-treated compared to untreated patients (P < 0.05). The data provide further evidence that leiomyomata express mRNA and protein for all components of the TGF beta system, and GnRHa therapy results in down-regulation of their expression. More specifically, these data suggest that TGF beta 1 and TGF beta 3 may play a more important role in leiomyomata growth than TGF beta 2, which leads us to propose that lowering TGF beta and receptor expression may have a direct effect on leiomyomata regression.

Adult↗
PubMed1996

Tumor necrosis factor-alpha stimulates aromatase gene expression in human adipose stromal cells through use of an activating protein-1 binding site upstream of promoter 1.4.

Expression of aromatase P450 (P450arom; the product of the CYP19 gene) in human adipose stromal cells in primary culture is markedly stimulated by serum in the presence of dexamethasone (DEX). Under these conditions, the majority of P450arom transcripts contain untranslated exon 1.4 at their 5'-ends. Previously, we observed that the region of the CYP19 gene upstream of exon 1.4 contains a TATA-less promoter, a glucocorticoid response element, and an interferon-gamma-activating sequence. These act to mediate the action of interleukin-6 and related cytokines to stimulate aromatase expression in the presence of DEX. In the present study, we found that tumor necrosis factor-alpha (TNF alpha) also acts synergistically with DEX to stimulate aromatase expression in adipose stromal cells in serum-free medium. We observed that the action of TNF alpha can be mimicked by ceramide. Maximal aromatase activity was obtained when cells were incubated with 5 ng/ml TNF alpha or 100 nM ceramide in the presence of 250 nM DEX. Levels of c-fos and c-jun proteins also were increased by TNF alpha or ceramide in the presence of DEX. Upstream of the interferon-gamma-activating sequence site there is an imperfect activating protein-1 (AP-1) binding site (2-bp mismatch). Gel retardation analysis using nucleotide probes containing the putative AP-1-binding sequence and nuclear extracts of human adipose stromal cells cultured in the presence of TNF alpha or ceramide plus DEX revealed that adipose stromal cells nuclear proteins bind to this site and that binding was competed by a 100-fold excess of a consensus AP-1 sequence. In addition, binding activity was competed by both anti-c-fos and anti-c-jun sera. Mutation or deletion of the putative AP-1 element resulted in the loss of TNF alpha- plus DEX-induced activity of reporter constructs comprised of 515 bp of the exon 1.4 flanking sequence linked to the luciferase gene. These results suggest that TNF alpha, probably acting through ceramide formation, stimulates the binding of both c-fos and c-jun to the AP-1 element upstream of exon 1.4. These act cooperatively with the ligand-activated glucocorticoid receptor to induce aromatase expression in adipose stromal cells in primary culture. We conclude that this TNF alpha signal transduction pathway may play an important role in the regulation of estrogen biosynthesis in adipose tissue.

Adipose Tissue↗
PubMed1996

Molecular forces involved in force generation during skeletal muscle contraction.

Recent advances in protein chemistry and the kinetic analysis of tension transients in skeletal muscle fibres have enabled us to elucidate the molecular forces involved in force generation by cross-bridges. On the basis of the temperature effect, we conclude that the elementary step that generates force is an endothermic reaction (the enthalpy change delta H degree = 124 kJ mol-1 at 15 degrees C), which accompanies a large entropy increase (delta S degree = 430JK-1 mol-1) and a reduction in the heat capacity (delta C p = -6.4kJ K-1 mol-1). Thus, it can be concluded that the force-generating step is an entropy-driven reaction. The above results suggest that hydrophobic interactions are the primary cause of force generation, and that polar interactions (hydrogen bonding and charge interactions) are involved to a lesser degree. On the basis of the thermodynamic data, we estimate that during force generation approximately 50 nm2 of surface area is involved for hydrophobic interactions and another 30 nm2 for polar interactions. These data suggest that both the actomyosin interaction and the cleft closure of the myosin head are essential for force generation.

Actins↗
PubMed1996

The relationship of fluorosis and brick tea drinking in Chinese Tibetans.

Brick tea-drinking fluorosis is an unusual environmental problem. As a result of an investigation of tea-drinking habits, total fluoride intakes, dental fluorosis, and skeletal fluorosis, this disease has been found in the Sichuan Province of China in Tibetans with a long history of drinking brick tea. The dental fluorosis investigation of 375 Tibetan children (213 males, 162 females) and 161 Han children (86 males, 75 females), 8-15 years of age, was carried out in Daofu County, Sichuan Province. According to the standard of the Chinese Health Ministry, a skeletal fluorosis survey of 658 Tibetans (264 males, 394 females) and 41 Hans (20 males, 11 females), all over 16 years old, was performed. The total fluoride intake and fluorosis were determined from a question--calculation method in all participants. The morbidities of dental fluorosis in Tibetan and Han children are 51.2% and 11.05%, respectively, and the indexes of dental fluorosis are 1.33 and 0.17 (chi 2 = 75.7, p < 0.01) respectively. The morbidity of skeletal fluorosis is 32.83% for Tibetan children and zero for the Han children. The fluoride intakes of Tibetan children and adults were 5.49 mg/person/day and 10.43 mg/person/day, respectively, in this area. Of total everyday fluoride intake, 94.2% by children and 94.4% by adults was from brick tea and zanba (r = 0.99).

Adolescent↗
PubMed1996

Pathologic changes in closed porcine intestinal loops inoculated with Aujeszky's disease virus.

Development of enteric lesions in closed jejunal and ileal loops inoculated with Aujeszky's disease virus (ADV) was examined in four 6-week-old SPF pigs. A large number of ADV antigens were detected first in necrotic foci in the subepithelial areas, and subsequently in the epithelial cells, lymphoid follicles in Peyer's patches and neuronal cells of Meissner's and Auerbach's plexuses.

Animals↗
PubMed1996

Protective effect of Tadenan on bladder function secondary to partial outlet obstruction.

PURPOSE: Tadenan (DEBAT, Paris, France) is a pharmaceutical agent used in the treatment of benign prostatic hyperplasia (BPH). The specific aim of this study was to determine if pretreatment of rabbits with Tadenan reduced either the hypertrophic response of the bladder to partial outlet obstruction or the accompanying contractile dysfunction. MATERIALS AND METHODS: Twenty-five male New Zealand rabbits (3 to 5 kg.) were separated into 5 groups of 5 rabbits each. Each rabbit in groups 1,2, and 3 received Tadenan orally at 1, 10 and 100 mg./kg./day for 3 weeks. Group 4 received vehicle only (peanut oil); Group 5 were controls. The bladders were evaluated (in vitro studies) after 2 weeks of obstruction. RESULTS: 1) Tadenan did not reduce the effect of partial outlet obstruction on bladder mass. 2) Tadenan pretreatment resulted in a significant protective effect on the contractile responses to field stimulation, bethanechol and KCl. CONCLUSIONS: These results clearly demonstrate that Tadenan pretreatment protected the bladder from the contractile dysfunctions induced by partial outlet obstruction.

Adenosine Triphosphate↗
PubMed1996

Mutation in and lack of expression of tyrosinase-related protein-1 (TRP-1) in melanocytes from an individual with brown oculocutaneous albinism: a new subtype of albinism classified as "OCA3".

Most types of human oculocutaneous albinism (OCA) result from mutations in the gene for tyrosinase (OCA1) or the P protein (OCA2), although other types of OCA have been described but have not been mapped to specific loci. Melanocytes were cultured from an African-American with OCA, who exhibited the phenotype of Brown OCA, and his normal fraternal twin. Melanocytes cultured from the patient with OCA and the normal twin appeared brown versus black, respectively. Melanocytes from both the patient with OCA and the normal twin demonstrated equal amounts of NP-40-soluble melanin; however, melanocytes from the patient with OCA contained only 7% of the amount of insoluble melanin found from the normal twin. Tyrosinase- related protein-1 (TRP-1) was not detected in the OCA melanocytes by use of various anti-TRP-1 probes. Furthermore, transcripts for TRP-1 were absent in cultured OCA melanocytes. The affected twin was homozygous for a single-bp deletion in exon 6, removing an A in codon 368 and leading to a premature stop at codon 384. Tyrosine hydroxylase activity of the OCA melanocytes was comparable to controls when assayed in cell lysates but was only 30% of controls when assayed in intact cells. We conclude that this mutation of the human TRP-1 gene affects its interaction with tyrosinase, resulting in dysregulation of tyrosinase activity, promotes the synthesis of brown versus black melanin, and is responsible for a third genetic type of OCA in humans, which we classify as "OCA3."

Albinism, Oculocutaneous↗
PubMed1996

[Studies on the cloning, expression and function of the yeast PHO 80 gene].

Through in situ hybridization, a 4.2 kb Pst I-BamH I fragment was obtained from S. cerevisiae gene library. The cloned fragment contained 1100 bp upstream sequence and 879 bp coding sequence of the PHO80 gene. Coding region of PHO80 gene was substituted with URA3 gene and used as donor to transform YPH499 to URA3. A pho80 mutant resulted from deletion of the chromosomal counterpart in PHO80 was obtained. In vivo functional study of the PHO80 gene indicated that PHO80 was a negative regulator in the Pi-repressible acid phosphatase system including the structural genes PHO5 and PHO11 and the regulatory gene PHO81, whereas the expression of PHO4 or PHO85 was independent of PHO80. The coding region of PHO80 was fused in frame with LacZ and beta-galactosidase activities in various cells was determined. The results Showed that the PHO80 gene was expressed at a low level and suppressed by itself and PHO85.

Acid Phosphatase↗
PubMed1996

Transcription of dopamine D1A receptor mRNAs in rat heart.

The existence of dopamine receptor subtypes in the heart has been suggested by pharmacological and biochemical techniques. So far, however, very little data is available as to the transcription of dopamine D1 subtype receptor genes in the heart. Therefore, in this study we employed reverse transcription-polymerase chain reaction (RT-PCR), which is a sensitive and highly specific method for identifying a low abundance mRNA in tissues, to determine if the D1A receptor gene was transcripted in the adult rat heart. Total RNA was isolated from the whole heart by the guanidium thiocyanate-CsCl method. Primers were based on the sequence of rat D1A cDNA cloned from the brain and corresponded to the third cytoplasmic loop of the receptor. A predicted size product (247bp) was evident from heart RNA. PCR performed in the absence of reverse transcriptase did not result in an amplification of the predicted product, indicating that these products were from cDNA and not from genomic DNA. The results demonstrate the existence of D1A receptor mRNA in the rat heart and that the D1A receptor in the heart are possibly identical to that from the brain. Since in this study the whole heart RNA was used, we cannot ascertain whether the mRNA comes from cardiac myocyte per se or from intermuscular coronary arterioles or from both.

Animals↗
PubMed1996

Scavenging effects of salvia miltiorrhiza on free radicals and its protection for myocardial mitochondrial membranes from ischemia-reperfusion injury.

Using low temperature electron spin resonance (ESR) technique, we found that Salvia miltiorrhiza injection could scavenge the oxygen free radicals generated from ischemia-reperfusion injury in the myocardium as effectively as SOD. Using ESR spin trapping technique we found that one of its effective components, Danshensu, could scavenge superoxide anion free radicals generated from the reaction system of xanthine and xanthine oxidase, and that lipid free radicals generated from lipid peroxidation of myocardial mitochondrial membranes could be scavenged by another effective component, Tanshinone. The membrane fluidity of the mitochondria isolated from the ischemia-reperfused hearts was studied with the ESR spin labelling technique, and the TBA-method was used to detect the lipid peroxidation. It was found that Danshensu could protect the mitochondrial membrane from the ischemia-reperfusion injury and lipid peroxidation.

Abietanes↗
PubMed1996

[The role of TNF alpha, IL-1 beta and MIP-1 alpha in LPS-induced organ injury].

OBJECTIVE: To investigate the role of inflammatory cytokines in endotoxemia models and to explore the possible anti-cytokine therapy of endotoxemia. METHODS: TNF alpha in plasma was measured by ELISA, and the mRNA of cytokines was assessed by slot blot analysis. RESULTS: LPS-induced TNF alpha release was in a dose:dependent manner in human whole blood. Dexamethasone (> or = 10(-8)mol/L) exhibited inhibitory effect on TNFa release. Ibuprofen 10(-7)-10(-9) mol/L had inhibitory effect on TNFa production, whereas 10(-3)-10(-4)mol/L stimulated TNFa release. The rat model of acute lung injury was made by LPS intraperitoneal injection. Both dexamethasone and ibuprofen that injected at 1 hour before LPS injection could decrease the contents of Evans blue in the lung (t 2.80 and 7.31 respectively, P < 0.05 vs LPS control). After LPS administered, there was a progressive up regulation in transcripts of TNF alpha, IL-1 beta and MIP-1 alpha in whole lung homogenates of rats. The mRNA peaked at 2, 6, 12 hours respectively. The TNF alpha, IL-1 beta and MIP-1 alpha mRNA levels decreased markedly when dexamethasone or ibuprofen given at 1 hour before LPS injection. CONCLUSION: TNF alpha, IL-1 beta and MIP-1 alpha play an essential role in the inflammatory response. LPS-induced acute lung injury may be prevented by dexamethasone and ibuprofen which have inhibitory effect on the gene expression of cytokines in the lung.

Animals↗
PubMed1996

Survival of cells with bleomycin-induced chromosomal lesions in the cultured lymphocytes of lung cancer patients.

In a previous study of lung cancer, we showed that bleomycin, a radiomimetic agent, induced breaks preferentially on chromosomes 4 and 5. The molecular cytogenetic study reported here, using chromosome painting and G banding, was designed to assess whether the chromatid breaks induced by bleomycin could survive as chromosome-type aberrations after treated lymphocyte populations were allowed to recover in a drug-free medium for one or two cell generations and whether the survival rates of lesions on chromosomes 4 and 5 differed in cases with lung cancer and controls. The findings from 16 cases and 14 controls showed that in samples allowed to recover for 48 h, most aberrations were of the chromosome type. The proportion of chromosome 5 abnormalities surviving as chromosome-type aberrations was significantly higher in the cells of lung cancer cases (13.4%) than in controls (4.6%; P < 0.0001). However, no significant differences in survival of chromosome 4 abnormalities were detected between cases and controls. The proportions of chromosome 5q13-q22 abnormalities were 5.3% in the cases and 0.6% in the controls (P < 0.0001). 5q13-q22 regions encompassed 38.4% of all abnormalities on chromosome 5 in the cases but only 14.5% in the controls. Therefore, the survival rate of chromosome 5 lesions (especially those at 5q13-q22) in lymphocytes might be used as a biomarker to identify populations at high risk for lung cancer.

Antibiotics, Antineoplastic↗