Search PubMed⌕ Search

Biomedical subjects

Y Zhao

Publications and source records attributed to Y Zhao.

At least 865 records · Page 48Linked to original sources
PubMed1995

TATA-binding protein residues implicated in a functional interplay between negative cofactor NC2 (Dr1) and general factors TFIIA and TFIIB.

The TATA-binding protein (TBP) plays a key role in transcription initiation. Several negative cofactors (NC1, NC2, and Dr1) are known to interact with TBP in a manner that prevents productive interactions of transcription factors TFIIA and TFIIB with promoter-bound TBP. To gain insights into the regulatory interplay on the surface of TBP, we have employed mutant forms of TBP to identify amino acid residues important for interactions with the negative regulatory cofactor NC2 and the general factor TFIIB. The results show the involvement of distinct domains of TBP in these interactions. Residues (Lys-133, Lys-145, and Lys-151) in the basic repeat region are important for interactions with NC2, as well as with TFIIA (Buratowski, S., and Zhou, H. (1992) Science 255, 1130-1132; Lee, D. K., DeJong, J., Hashimoto, S., Horikoshi, M., and Roeder, R. G. (1992) Mol. Cell. Biol. 12, 5189-5196), whereas a residue (Leu-189) in the second stirrup-like loop spanning S2' and S3' is required for interaction with TFIIB. In addition, we demonstrate that NC2 is identical to the previously cloned negative cofactor Dr1. The implications of these results for TBP structure and function are discussed.

Binding Sites↗
PubMed1995

Assignment of the XRCC2 human DNA repair gene to chromosome 7q36 by complementation analysis.

The V79 hamster cell line irs1 is a repair-deficient mutant hypersensitive to radiation and DNA-reactive chemical agents. Somatic cell hybrids were formed by fusing irs1 cells with human lymphocytes and selecting for complementation in medium containing concentrations of mitomycin C (MMC) that are toxic to irs1. Thirty-eight MMC-resistant hybrids showed extensive segregation of human chromosomes, with 35 of them retaining human chromosome 7, as indicated by molecular marker and cytogenetic analyses. Inter-Alu-PCR products from the DNA of hybrids, when used as fluorescence in situ hybridization probe onto normal human metaphases, indicated that one resistant hybrid was monochromosomal for chromosome 7 and that the three resistant hybrids shown to be negative for chromosome 7 markers have retained portions of chromosome 7, with region 7q36 being the smallest common region. MMC-sensitive subclones of a resistant hybrid lost human chromosome 7. Therefore, the gene complementing the repair defect, XRCC2 (X-ray repair cross complementing), is assigned to human chromosome 7q36.

Animals↗
PubMed1995

Regulation by physical training of enzyme activity and gene expression of branched-chain 2-oxo acid dehydrogenase complex in rat skeletal muscle.

We examined the effects of short-term (5 weeks) and long-term (12 weeks) physical training on actual and total activities, protein content and mRNA abundance of branched-chain 2-oxo acid dehydrogenase complex in rat skeletal muscle. The actual and total activities were significantly increased approximately 60% and approximately 40%, respectively, by long-term training. No effects of short-term training on activities were observed. The increase in the total activity corresponded to increased protein content of the E1 alpha and E2 components of the complex. On the other hand, mRNA abundance for E1 alpha and E2 were not affected by the training, but that for E1 beta was slightly, but significantly increased by both short-term and long-term trainings. These divergent alterations of the message levels for the subunits of the complex suggest that posttranslational regulatory mechanisms determine the amount of the complex in skeletal muscle. Since the complex is located in the mitochondrial matrix space, mitochondrial biogenesis in response to the training was examined by determining the content of mitochondrial DNA in the muscle. The mitochondrial DNA was proportionally increased with the total activity as well as the protein content of the complex, suggesting that expression of branched-chain 2-oxo acid dehydrogenase complex in skeletal muscle in response to physical training is associated with mitochondrial biogenesis.

3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)↗
PubMed1995

Dietary control and tissue specific expression of branched-chain alpha-ketoacid dehydrogenase kinase.

The branched-chain alpha-ketoacid dehydrogenase complex, catalyst for the rate-limiting step of branched-chain amino acid catabolism, is controlled by a highly specific protein kinase (branched-chain alpha-ketoacid dehydrogenase kinase) that associates tightly with the complex. The activity state (proportion of the enzyme in its active, dephosphorylated state) of the complex varies dramatically in different rat tissues. The activity state of the complex in the liver is greater than that in any other tissue, and liver contains the lowest amount of kinase protein and kinase mRNA. However, protein malnutrition, a condition under which the complex is largely phosphorylated and inactive, resulted in a three- to fourfold increase in hepatic kinase activity with an accompanying increase in amounts of kinase protein and mRNA. Refeeding a 50% protein diet restored the normal activity state and the original levels of kinase protein and mRNA. The amount of kinase protein associated with the complex rather than changes in specific activity of the kinase appears responsible for observed differences in activity states of the complex in several rat tissues tested. Accordingly, the levels of kinase protein and mRNA measured are highest in tissues with greatest kinase activity (heart > kidney > liver), correlating reasonably well inversely with activity state of the branched-chain alpha-ketoacid dehydrogenase complex in the respective tissues. These observations suggest that the amount of kinase protein expressed in various tissues and in response to dietary protein deficiency is an important factor determining the activity state of the complex.

3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)↗
PubMed1995

Oestradiol inhibition of vascular myointimal proliferation following immune, chemical and mechanical injury.

The lower incidence of coronary artery disease in premenopausal women and in postmenopausal women treated with oestrogen supports the hypothesis that oestrogen protects the vasculature from injuries or from responding to injuries with arteriosclerosis. The mechanism remains unknown, although currently the most frequent suggestion is that oestrogen induces beneficial quantitative and qualitative changes in serum lipoprotein concentrations. We studied other mechanisms and in particular the direct effects of 17 beta-oestradiol on vascular smooth muscle and the endothelium. Our focus has been on the vascular response to injury by myointimal and medial thickening, leading to narrowing or occlusion of the vessel. This is frequently seen in coronary arteries within months following angioplasty and a few years following cardiac transplantation. We find that oestradiol treatment protects and reduces the vascular response to injury in three in vivo and one in vitro models: (1) in the rabbit cardiac allograft where oestrogen inhibits accelerated graft atherosclerosis; (2) in monocrotaline- or hypoxia-induced pulmonary hypotension in the rat, where oestrogen attenuates pulmonary artery pressure, right ventricular hypertrophy and medial thickening of the pulmonary artery; (3) oestrogen protects against balloon injury in rabbit aorta; and (4) it inhibits smooth muscle cell proliferation in the porcine left anterior descending coronary artery.

Animals↗
PubMed1995

Enhanced expression of novel CD57+CD8+ LAK cells from cats infected with feline immunodeficiency virus.

As a model for lymphokine-activated killer (LAK) function in HIV infection, we studied LAK cells in cats infected with feline immunodeficiency virus (FIV), which causes an acquired immunodeficiency syndrome. Peripheral blood mononuclear cells cultured in concanavalin A and interleukin-2 developed LAK cytotoxicity against chronically FIV-infected CrFK cells and acutely infected CD4+ lymphocytes but not uninfected cells. LAK cells from FIV+ cats were more cytotoxic than LAK cells from uninfected cats. Enhanced FIV+ LAK cytotoxicity against feline leukemia virus-infected cells (FL74) suggested that the cytotoxicity was not antigen specific. Two-color fluorescence-activated cell sorter analysis and antibody depletion studies demonstrated that the majority of LAK cells and their progenitors were positive for both CD8 and CD57. The in vitro induction of dual positive CD8+CD57+ LAK cells was enhanced in FIV+ cats, as reported for HIV+ patients. These CD8+CD57+ LAK cells may play a role in maintaining the long asymptomatic stage of infection in FIV+ cats.

Animals↗
PubMed1995

Analysis of randomly isolated cDNAs from developing endosperm of rice (Oryza sativa L.): evaluation of expressed sequence tags, and expression levels of mRNAs.

Using a cDNA library prepared from poly(A)+ RNA from 10-day-old rice endosperm, partial nucleotide sequences of randomly isolated clones were analyzed. A total of 153 (30.6%) out of 500 cDNA clones showed high amino acid identity to previously identified genes. There was significant redundancy in cDNAs encoding prolamine and glutelin. About 21.0% of the cDNA clones were found to code for seed storage protein genes. Consequently, 37 independent genes were identified. Using cDNA clones encoding glutelin, prolamine, seed allergen, alpha-1,4-glucan branching enzyme, glycine-rich RNA binding protein, metallothionein, non-specific lipid-transfer protein and ubiquitin conjugating enzyme the accumulation of mRNA during rice seed development was compared. Genes associated with seed storage protein and starch biosynthesis were expressed according to expected developmental stages. Glycine-rich RNA binding protein genes as well as metallothionein-like protein genes were highly expressed in developing seeds, but low in leaves of whole plants.

Blotting, Northern↗
PubMed1995

Rheumatoid arthritis in the northeastern area of the People's Republic of China and western Japan.

The clinical features of 134 consecutive hospitalized patients with rheumatoid arthritis in the northeastern area of the People's Republic of China and 251 consecutive hospitalized patients from western Japan were compared. A total of 91.8% of the Chinese patients were of Han nationality, while all of the patients from Japan were Japanese. The patients in the People's Republic of China showed more inflammatory articular disease and more frequent subcutaneous nodules than did the Japanese patients in the presence of a less elevated ESR value and less radiographic joint destruction. The clinical features of the patients of Han nationality and the Japanese did not change even after adjusting the patients' age and disease duration. The reasons for the contradictory features in the Chinese patients still remain to be clarified. This study is hopefully a first step in promoting more precise studies on rheumatoid arthritis in the People's Republic of China.

Adult↗
PubMed1995

Angiopeptin, a somatostatin-14 analogue, decreases adhesiveness of rat leukocytes to unstimulated and IL-1 beta-activated rat heart endothelial cells.

We have previously demonstrated that somatostatin-14 and its octapeptide analogue, angiopeptin, decrease the ability of rat heart endothelial cells to bind leukocytes [Leszczynski, et al., Reg. Pept. 43 (1993) 131-140]. Here, we examined whether exposure of leukocytes to angiopeptin modifies their adhesiveness to the unstimulated and to IL-1 beta-activated endothelium. Monolayers of unstimulated endothelial cells bind 274 +/- 12 leukocytes/mm2. Exposure of leukocytes for 1, 4 and 24 hours to angiopeptin (1 microM) reduced significantly (p < 0.05) adhesion of leukocytes from 274 +/- 12 to 188 +/- 10, 185 +/- 8 and 172 +/- 3 cells/mm2, respectively. Stimulation of endothelial cells with Il-1 beta (100 U/ml) for 24 hours increased endothelial adhesiveness from 274 +/- 12 to 381 +/- 17 adhering leukocytes/mm2. Exposure of leukocytes for 1, 4 and 24 hours to angiopeptin (1 microM) reduced significantly (p < 0.05) binding of leukocytes to IL-1 beta-activated endothelium from 381 +/- 17 to 237 +/- 8, 254 +/- 11 and 248 +/- 13 cells/mm2, respectively. Angiopeptin had no effect on the expression of lymphocyte function-associated molecule-1 (LFA-1; CD11a/CD18) by leukocytes, as assessed by flow cytometry. This suggests that angiopeptin modulates adhesive properties of leukocytes by (1) altering the expression of other than LFA-1 adhesion molecule(s) and/or (2) modulating the affinity of adhesion molecule(s) expressed by leukocytes. In conclusion, our results demonstrate that angiopeptin reduces leukocyte adhesiveness to unstimulated and to IL-1 beta-activated endothelium. It suggests that angiopeptin may suppress immune response via modulation of the leukocyte-endothelial interaction.

Animals↗
PubMed1995

Chronic hypoxia impairs pulmonary venous smooth muscle contraction.

Chronic hypoxia increases total pulmonary vascular resistance and causes pulmonary hypertension. Although the effect of chronic hypoxia on pulmonary arterial tissue has been extensively studied, very little is known about the effects on the pulmonary vein. The purpose of the present investigation was to determine the effect of chronic hypoxia on pulmonary venous reactivity to several vasoactive agonists and on the venous response to acute hypoxia. Isolated pulmonary venous rings were taken from rats exposed to 2, 7, and 14 days of hypoxia (FIO2 = 0.1). A decrease in the response of the pulmonary vein to KCl was observed after 14 days of hypoxia. The reactivity (maximum active force produced) of the pulmonary vein in response to phenylephrine (PE) was reduced after 7 days of hypoxia. The response of the pulmonary vein to angiotensin II (AII) was more sensitive to the effects of chronic hypoxia since decreased reactivity to angiotensin II occurred after only 2 days of hypoxia. Prolonged hypoxia (14 days) had no further effect on the decreased reactivities to PE and AII. The sensitivities of pulmonary venous muscle to PE and AII were decreased (increased ED50 values) by 2 days of chronic hypoxia, but tended to return to control levels after 7 and 14 days of hypoxia. However, the contractile response of the pulmonary vein to acute hypoxia was not changed even after 14 days of chronic hypoxia. These results suggest that chronic hypoxia: (1) impairs pulmonary venous smooth muscle contractility; (2) reduces pulmonary venous reactivity and sensitivity to phenylephrine and angiotensin II; and (3) does not alter the pulmonary venous contractile response to acute hypoxia.

Angiotensin II↗
PubMed1995

A new family of protein kinases--the mitochondrial protein kinases.

Molecular cloning has provided evidence for a new family of protein kinases in eukaryotic cells. These kinases show no sequence similarity with other eukaryotic protein kinases, but are related by sequence to the histidine protein kinases found in prokaryotes. These protein kinases, responsible for phosphorylation and inactivation of the branched-chain alpha-ketoacid dehydrogenase and pyruvate dehydrogenase complexes, are located exclusively in mitochondrial matrix space and have most likely evolved from genes originally present in respiration-dependent bacteria endocytosed by primitive eukaryotic cells. Long-term regulatory mechanisms involved in the control of the activities of these two kinases are of considerable interest. Dietary protein deficiency increases the activity of branched-chain alpha-ketoacid dehydrogenase kinase associated with the branched-chain alpha-ketoacid dehydrogenase complex. The amount of branched-chain alpha-ketoacid dehydrogenase kinase protein associated with the branched-chain alpha-ketoacid dehydrogenase complex and the message level for branched-chain alpha-ketoacid dehydrogenase kinase are both greatly increased in the liver of rats starved for protein, suggesting increased expression of the gene encoding branched-chain alpha-ketoacid dehydrogenase kinase. The increase in branched-chain alpha-ketoacid dehydrogenase kinase activity results in greater phosphorylation and lower activity of the branched-chain alpha-ketoacid dehydrogenase complex. The metabolic consequence is conservation of branched chain amino acids for protein synthesis during periods of dietary protein deficiency. Two isoforms of pyruvate dehydrogenase kinase have been identified and cloned. Pyruvate dehydrogenase kinase 1, the first isoform cloned, corresponds to the 48 kDa subunit of the pyruvate dehydrogenase kinase isolated from rat heart tissue. Pyruvate dehydrogenase kinase 2, the second isoform cloned, corresponds to the 45 kDa subunit of this enzyme. In addition, it also appears to correspond to a possibly free or soluble form of pyruvate dehydrogenase kinase that was originally named kinase activator protein. Assuming that differences in kinetic and/or regulatory properties of these isoforms exist, tissue specific expression of these enzymes and/or control of their association with the complex will probably prove to be important for the long term regulation of the activity of the pyruvate dehydrogenase complex. Starvation and the diabetic state are known to greatly increase activity of the pyruvate dehydrogenase kinase in the liver, heart and muscle of the rat. This contributes in these states to the phosphorylation and inactivation of the pyruvate dehydrogenase complex and conservation of pyruvate and lactate for gluconeogenesis.(ABSTRACT TRUNCATED AT 400 WORDS)

3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)↗
PubMed1995

Cloning and expression of cytochrome P450(11 beta) of porcine adrenal cortex.

Four cDNA clones were isolated from a porcine adrenal gland library by using a bovine cytochrome P450(11 beta) cDNA fragment as a probe. Nucleotide sequences of the four clones overlapped with each other. The deduced amino acid sequences indicated that these clones were derived from a porcine P450(11 beta) cDNA. Consecutive alignment of these clones covered almost 70% of a coding region of the cDNA, but its 5'-terminus was missing. The adrenal mRNA was reverse-transcribed, and polymerase chain reaction was used to obtain a cDNA fragment including the 5'-terminus. A cDNA constructed from this fragment and the isolated four fragments covered the entire apparent open reading frame of the enzyme, which was thus concluded to comprise 503 amino acids including a putative extension peptide of 24 amino acids at the NH2-terminus. The amino acid sequence was 82% identical to that of bovine P450(11 beta)-3. The cDNA was transfected into COS-7 cells, and steroidogenic activity of the cells was measured. The cells not only converted 11-deoxycorticosterone to corticosterone and 18-hydroxycorticosterone, but also produced aldosterone. Thus we conclude that the primary sequence of porcine P450(11 beta) which plays a role in the biosynthesis of glucocorticoids as well as mineralocorticoids was determined.

18-Hydroxycorticosterone↗
PubMed1995

A stochastic model of leukocyte rolling.

Selectin-mediated leukocyte rolling under flow is an important process in leukocyte recruitment during inflammation. The rolling motion of individual cells has been observed to fluctuate randomly both in vivo and in vitro. This paper presents a stochastic model of the micromechanics of cell rolling and provides an analytical method of treating experimental data. For a homogeneous cell population, the velocity distribution is obtained in an analytical form, which is in good agreement with experimentally determined velocity histograms obtained previously. For a heterogeneous cell population, the model provides a simple, analytical method of separating the contributions of temporal fluctuations and population heterogeneity to the variance of measured rolling velocities. The model also links the mean and variance of rolling velocities to the molecular events underlying the observed cellular motion, allowing characterization of the distribution and release rate of the clusters of molecular bonds that tether the cell to substratum. Applying the model to the analysis of data obtained for neutrophils rolling on an E-selectin-coated surface at a wall shear stress of 1.2 dyn/cm2 yields estimations of the average distance between bond clusters (approximately micron) and the average time duration of a bond cluster resisting the applied fluid force (approximately 0.5 s).

Cell Membrane↗
PubMed1995

Selective sparing of human nucleus accumbens in aging and anoxia.

OBJECTIVE: To investigate the effects of aging and anoxia on the nucleus accumbens. METHODS: The number of neurons in nucleus accumbens and caudate nucleus in 35 patients over 65 and 35 under 65 years, all without neurological or psychiatric disease were counted. RESULTS: There was no statistically significant difference between the number of neurons in the accumbens in the two groups, but there was a decrease in the number of neurons in the elderly group. There was no reduction in volume of the neuronal nucleoli of the accumbens measured in 12 elderly patients compared to controls. These data suggest a sparing of the accumbens from changes associated with aging. There was relative preservation of the nucleus accumbens in 3 patients with anoxic encephalopathy. CONCLUSIONS: These results show that accumbens was resistant to both aging and anoxia, the mechanism of which is discussed.

Adult↗