Biomedical subjects

Y Zhang

Publications and source records attributed to Y Zhang.

At least 487 records · Page 27Linked to original sources

PubMed2001

Regulation of Smad degradation and activity by Smurf2, an E3 ubiquitin ligase.

Smad proteins are key intracellular signaling effectors for the transforming growth factor-beta superfamily of peptide growth factors. Following receptor-induced activation, Smads move into the nucleus to activate transcription of a select set of target genes. The activity of Smad proteins must be tightly regulated to exert the biological effects of different ligands in a timely manner. Here, we report the identification of Smurf2, a new member of the Hect family of E3 ubiquitin ligases. Smurf2 selectively interacts with receptor-regulated Smads and preferentially targets Smad1 for ubiquitination and proteasome-mediated degradation. At higher expression levels, Smurf2 also decreases the protein levels of Smad2, but not Smad3. In Xenopus embryos, ectopic Smurf2 expression specifically inhibits Smad1 responses and thereby affects embryonic patterning by bone morphogenetic protein signals. These findings suggest that Smurf2 may regulate the competence of a cell to respond to transforming growth factor-beta/bone morphogenetic protein signaling through a distinct degradation pathway that is similar to, yet independent of, Smurf1.

Acetylcysteine↗

PubMed2001

Giant enhancement of the thermal Hall conductivity kappa(xy) in the superconductor YBa(2)Cu(3)O(7).

In high-purity YBa(2)Cu(3)O(7), the (weak-field) thermal Hall conductivity kappa(xy) is observed to increase a thousand-fold between 90 and 30 K. The inferred quasiparticle lifetime tau increases a hundred-fold starting below 90 K, in disagreement with a recent photoemission experiment. We show that kappa(xy) exhibits a specific scaling behavior below approximately 30 K. This scaling may bear on the issue of whether Landau quantization of the quasiparticle states occurs.

Journal Article↗

PubMed2001

Differential expression of human nucleoside transporters in normal and tumor tissue.

Responses to nucleoside analog drugs used in the treatment of cancers and viral infections can vary considerably between individuals. Genetic variability between individuals in their ability to transport drugs may be a contributory factor. Nucleoside transporters (NTs) move nucleosides and analog drugs across cell membranes. Four human NTs have been cloned: hENT1, hENT2, hCNT1, and hCNT2. Human NT expression profiles are not well defined; therefore, we undertook a comprehensive quantitative analysis of the differential expression of NTs within normal and tumor tissue. Results show tissue specific expression of the different NTs in normal tissue while matched normal/tumor tissue cDNA array data show considerable variability in all NT expression profiles from different individuals, in particular decreased expression in tumor tissue. Decreased NT expression in tumor tissue may contribute to reduced drug uptake and the development of resistance. These data suggest that nucleoside analog drug therapies may be optimized by determining individual NT expression profiles.

Antineoplastic Agents↗

PubMed2001

[Analysis of 2200 kidney transplantations].

OBJECTIVE: To analyze the clinical results of 2 200 renal transplantations. METHODS: The following factors were analyzed: (1) the graft survival rates at 1, 3 and 5 years; (2) main factors contributing to the mortality; (3) factors affecting the survival rate of retransplant grafts; (4) features of cancers after renal transplantation; (5) effect of CSA on liver function after renal transplantation; (6) treatments for chronic rejection; and (7) effect of HLA typing on renal transplantation. RESULTS: From 1972 to 2000, 2 200 renal transplantations were performed in 1 908 patients (1 337 men and 571 women) with end-stage renal failure in our hospital, Beijing. The graft survival rates at 1, 3 and 5 years were 87.3%, 80.2% and 67.0% respectively, after using CSA since 1985. 302 recipients were aged over 50 years whose one year graft survival rate was 83.4% and one year patient survival rate was 85.4%. Pneumonitis was the dominant death factor after renal transplantation, with an incidence of 4.49% and a death rate of 34.62%. The incidence of positive CMV after renal transplantation was up to 40.3%, in with a death rate of 8.0%. The incidence of tumor after renal transplantation was 1.5%. The most frequent site of tumor was urological system. The patient's liver function before transplantation and the intraindividual variability of bioavailabity to CSA etc. were the major toxic factors of the liver. The incidences of acute rejection were 27%, 35.5%, 22.4%, 20.85%, 0% and 0%, respectively, when the HLA mismatches were 6, 5, 4, 3, 2 and 1. CONCLUSION: Using immunosuppressents reasonably, preventing acute rejection, and achieving good HLA typing are the major factors improving long-term graft/patient survival rate.

Adolescent↗

PubMed2001

MAP kinases mediate UVB-induced phosphorylation of histone H3 at serine 28.

Histone H3 phosphorylation is related closely to chromatin remodeling and chromosome condensation. H3 phosphorylation at serine 28 is coupled with mitotic chromosome condensation in diverse mammalian cell lines. However, the pathway that mediates phosphorylation of H3 at serine 28 is unknown. In the present study, ERK1, ERK2, or p38 kinase strongly phosphorylated H3 at serine 28 in vitro. JNK1 or JNK2 was able also to phosphorylate H3 at serine 28 in vitro but to a lesser degree. UVB irradiation markedly induced phosphorylation of H3 at serine 28 in JB6 Cl 41 cells. PD 98059, a MEK1 inhibitor, and SB 202190, a p38 kinase inhibitor, efficiently repressed UVB-induced H3 phosphorylation at serine 28. Expression of dominant negative mutant (DNM) ERK2 in JB6 Cl 41 cells totally blocked UVB-induced phosphorylation of H3 at serine 28. Additionally, DNM p38 kinase or DNM JNK1 partially blocked UVB-induced H3 phosphorylation at serine 28. Furthermore, UVB-induced H3 phosphorylation at serine 28 was inhibited in Jnk1(-/-) cells but not in Jnk2(-/-) cells. These results suggest that UVB-induced H3 phosphorylation at serine 28 may be mediated by mitogen-activated protein kinases.

Animals↗

PubMed2001

Partial synchronization and spontaneous spatial ordering in coupled chaotic systems.

A model of many symmetrically and locally coupled chaotic oscillators is studied. Partial chaotic synchronizations associated with spontaneous spatial ordering are demonstrated. Very rich patterns of the system are revealed, based on partial synchronization analysis. The stabilities of different partially synchronous spatiotemporal structures and some dynamical behaviors of these states are discussed both numerically and analytically.

Journal Article↗

PubMed2001

The MinE ring required for proper placement of the division site is a mobile structure that changes its cellular location during the Escherichia coli division cycle.

Placement of the division site at midcell in Escherichia coli requires the MinE protein. MinE acts by imparting topological specificity to the MinCD division inhibitor, preventing the inhibitor from acting at the midcell site while permitting it to block division at other unwanted sites along the length of the cell. It was previously shown that MinE assembled into a ring structure that appeared to be localized near midcell, apparently explaining the ability of MinE to specifically counteract MinCD at midcell. We report here that the MinE ring is not fixed in position near midcell but is a dynamic structure that undergoes a repetitive cycle of movement first to one cell pole and then to the opposite pole. Taken together with studies of the dynamic behavior of the MinD protein, the results suggest that the topological specificity of division site placement may not involve a localized action of MinE to counteract the MinCD division inhibitor at midcell but rather the ability of MinE to move the division inhibitor away from midcell and to the cell poles.

Adenosine Triphosphatases↗

PubMed2001

Involvement of the acid sphingomyelinase pathway in uva-induced apoptosis.

The sphingomyelin-ceramide pathway is an evolutionarily conserved ubiquitous signal transduction system that regulates many cell functions including apoptosis. Sphingomyelin (SM) is hydrolyzed to ceramide by different sphingomyelinases. Ceramide serves as a second messenger in mediating cellular effects of cytokines and stress. In this study, we find that acid sphingomyelinase (SMase) activity was induced by UVA in normal JY lymphoblasts but was not detectable in MS1418 lymphoblasts from Niemann-Pick type D patients who have an inherited deficiency of acid SMase. We also provide evidence that UVA can induce apoptosis by activating acid SMase in normal JY cells. In contrast, UVA-induced apoptosis was inhibited in MS1418 cells. Exogenous SMase and its product, ceramide (10-40 micrometer), induced apoptosis in JY and MS1418 cells, but the substrate of SMase, SM (20-80 micrometer), induced apoptosis only in JY cells. These results suggest that UVA-induced apoptosis by SM is dependent on acid SMase activity. We also provide evidence that induction of apoptosis by UVA may occur through activation of JNKs via the acid SMase pathway.

Animals↗

PubMed2001

Conjugation of brain-derived neurotrophic factor to a blood-brain barrier drug targeting system enables neuroprotection in regional brain ischemia following intravenous injection of the neurotrophin.

Neurotrophins such as brain-derived neurotrophic factor (BDNF) are potential neuroprotective agents that could be used in the treatment of acute stroke, should these proteins be made transportable through the blood-brain barrier (BBB) in vivo. One approach to the BBB problem is to attach the nontransportable peptide to a brain targeting vector, which is a peptide or peptidomimetic monoclonal antibody (MAb), that is transported into brain from blood via an endogenous BBB transport system. The present studies describe a conjugate of BDNF and the OX26 monoclonal antibody (MAb) to the transferrin receptor. Avidin-biotin technology is used to link the BDNF and the MAb. The surface of the BDNF is conjugated with 2000 Da polyethylene glycol at carboxyl residues to optimize the plasma pharmacokinetics of the neurotrophin. Adult rats subjected to 24 h of permanent middle cerebral artery occlusion (MCAO) were treated intravenously with either unconjugated BDNF, unconjugated MAb, or the BDNF-OX26 conjugate at a dose of 1, 5 and 50 microg/rat of the BDNF. These doses decreased the infarct volume by 6% (not significant), 43% (P<0.01), and 65% (P<0.01), respectively. Significant reduction in stroke volume was still observed if the administration of the BDNF conjugate was delayed for 1-2 h after MCAO, although the pharmacological effect was progressively diminished in proportion to the time delay between MCAO and treatment. In conclusion, these studies demonstrate that large reductions in stroke volume can be achieved with the noninvasive intravenous administration of neurotrophins such as BDNF, providing the peptide is conjugated to a BBB drug targeting system.

Animals↗

PubMed2001

Role of endogenous opioid peptides in protection of ischemic preconditioning in rat small intestine.

This study investigated the protective effects of ischemic preconditioning on intestinal ischemic injury and the role of endogenous opioid peptides (EOP) in these effects. Ischemia-reperfusion (I/R) induced by 30-min of ischemia and 60-min of reperfusion significantly increased the levels of malondialdehyde (MDA) and lactate dehydrogenase (LDH) and resulted in serious intestinal edema (wet weight/dry weight). The ischemic preconditioning (PC) elicited by three 8-min occlusion periods interspersed with 10-min reperfusion markedly attenuated intestinal injury caused by ischemia-reperfusion. Pretreatment with morphine (300 microg x kg(-1), i.v.) 10-min before ischemia and reperfusion mimicked the protection produced by PC. Naloxone (3 mg x kg(-1), i.v.) abolished the protection of morphine-induced preconditioning and ischemic preconditioning in rat intestine. However, there were no changes between naloxone alone and control groups. Treatment with naloxone before ischemia-reperfusion had no effect on animals compared with the I/R group. In addition, we also measured the content of endogenous opioid peptides (Leu-enkephalin) in the effluent which was collected before and during preconditioning. It was shown that the release of leu-enkephalin was markedly increased during preconditioning. These results suggested that EOP might play an important role in PC in rat small intestine.

Analgesics, Opioid↗

PubMed2001

Mechanisms for LEPR-mediated regulation of leptin expression in brown and white adipocytes in rat pups.

To investigate the underlying mechanisms for leptin receptor (LEPR)-mediated regulation of leptin gene (Lep) expression in brown (BAT) and white (WAT) adipose tissue and resultant effects on plasma leptin concentrations (plasma-LEP), we examined effects of sympathetic nervous system (SNS) activity, caloric balance, and body fat content on leptin mRNA levels in BAT and WAT in 10-day-old rat pups segregating for Lepr(fa). In mother-reared pups, Lep mRNA levels were fa/fa > +/fa = +/+ in BAT and was fa/fa > +/fa > +/+ in WAT. The genotype effects on Lep expression in BAT and plasma-LEP were virtually eliminated when the differences in SNS activity between fa/fa and +/fa pups were equalized by artificial rearing of pups under thermoneutral conditions with or without oral norepinephrine (NE) administration. NE administration alone had little effect on the Lepr(fa)-dependent stratification of Lep expression in WAT. BAT-Lep mRNA was the main determinant of plasma-LEP. Metabolic rate, a surrogate indicator of SNS activity, explained 87% of the variation in BAT-Lep mRNA (R(2) = 0.93), whereas caloric balance (40%) and body fat mass (6%) accounted for most of the variation in WAT-Lep mRNA (R(2) = 0.53). We conclude that feedback regulation of Lep expression in BAT is primarily via central nervous system-mediated effects of leptin on SNS activity, whereas the control of leptin expression in WAT is more likely via mechanisms not directly dependent on SNS activity.

Adipocytes↗

PubMed2001

Frequency of specific cancer types in dermatomyositis and polymyositis: a population-based study.

BACKGROUND: Dermatomyositis and polymyositis are associated with cancer, but previous nationwide studies have not had sufficient cases to test the association between myositis and specific cancer types. Our aim was to investigate the risk of specific cancer types in individuals with dermatomyositis and polymyositis. METHODS: We did a pooled analysis of published national data from Sweden, Denmark, and Finland. All patients with dermatomyositis and polymyositis (> or =15 years old) were identified by discharge diagnosis from the Swedish National Board of Health (1964-83), Danish Hospital Discharge Registry (1977-89), and Finnish National Board of Health (1969-85). Personal details were matched to national cancer registries, to identify all cases of cancer up to 1987 in Sweden, 1995 in Denmark, and 1997 in Finland, and to national death registries for the same periods. We calculated standardised incidence ratios (SIR) for individual cancer sites for dermatomyositis and polymyositis separately, using national cancer rates by country, sex, age, and date. FINDINGS: We identified 618 cases of dermatomyositis, of whom 198 had cancer. 115 of the 198 developed cancer after diagnosis of dermatomyositis. This disease was strongly associated with malignant disease (SIR 3.0, 95% CI 2.5-3.6), particularly ovarian (10.5, 6.1-18.1), lung (5.9, 3.7-9.2), pancreatic (3.8, 1.6-9.0), stomach (3.5, 1.7-7.3), and colorectal (2.5, 1.4-4.4) cancers, and non-Hodgkin lymphoma (3.6, 1.2-11.1). 137 of the 914 cases of polymyositis had cancer, which developed after diagnosis of polymyositis in 95. Polymyositis was associated with a raised risk of non-Hodgkin lymphoma (3.7, 1.7-8.2), and lung (2.8, 1.8-4.4) and bladder cancers (2.4, 1.3-4.7). In both dermatomyositis and polymyositis, risk of malignant disease was highest at time of myositis diagnosis. INTERPRETATION: Our results provide evidence that dermatomyositis is strongly associated with a wide range of cancers. The overall risk of malignant disease is also modestly increased among patients with polymyositis, with an excess for some cancers.

Dermatomyositis↗

PubMed2001

Thyroid hormone stimulates acetyl-coA carboxylase-alpha transcription in hepatocytes by modulating the composition of nuclear receptor complexes bound to a thyroid hormone response element.

Triiodothyronine (T3) stimulates a 7-fold increase in transcription of the acetyl-CoA carboxylase-alpha (ACCalpha) gene in chick embryo hepatocytes. Here, we characterized an ACCalpha T3 response element (ACCalpha-T3RE) with unique functional and protein binding properties. ACCalpha-T3RE activated transcription both in the absence and presence of T3, with a greater activation observed in the presence of T3. In nuclear extracts from hepatocytes incubated in the absence of T3, ACCalpha-T3RE bound protein complexes (complexes 1 and 2) containing the liver X receptor (LXR) and the retinoid X receptor (RXR). In nuclear extracts from hepatocytes incubated in the presence of T3 for 24 h, ACCalpha-T3RE bound a different set of complexes. One complex contained LXR and RXR (complex 3) and another contained the nuclear T3 receptor (TR) and RXR (complex 4). Mutations of ACCalpha-T3RE that inhibited the binding of complexes 1 and 2 decreased transcriptional activation in the absence of T3, and mutations of ACCalpha-T3RE that inhibited the binding of complexes 3 and 4 decreased transcriptional activation in the presence of T3. The stimulation of ACCalpha transcription caused by T3 was closely associated with changes in the binding of complexes 1-4 to ACCalpha-T3RE. These data suggest that T3 regulates ACCalpha transcription by a novel mechanism involving changes in the composition of nuclear receptor complexes bound to ACCalpha-T3RE. We propose that complexes containing LXR/RXR ensure a basal level of ACCalpha expression for the synthesis of structural lipids in cell membranes and that complexes containing LXR/RXR and TR/RXR mediate the stimulation of ACCalpha expression caused by T3.

Acetyl-CoA Carboxylase↗

PubMed2001

Nuclear translocation of the N-terminal prodomain of interleukin-16.

Interleukin-16 (IL-16) is a pleiotropic cytokine that functions as a chemoattractant factor, a modulator of T cell activation, and an inhibitor of human immunodeficiency virus (HIV) replication. These diverse functions are exclusively attributed to the secreted C-terminal peptide of 121 amino acids (mature IL-16), which is cleaved from the precursor protein (pro-IL-16) by caspase-3. Human pro-IL-16 is comprised of 631 amino acids with three PDZ domains, one of which is present in secreted mature IL-16. No cellular localization or biologic functions have been ascribed to the unusually large and highly conserved N-terminal prodomain formed as a result of proteolytic release of the third PDZ domain of pro-IL-16. Here we show that the N-terminal prodomain of pro-IL-16 translocates into the nucleus following cleavage of the C-terminal segment. The nuclear localization signal of pro-IL-16 consists of a classical bipartite nuclear targeting motif. We also show that the nuclear targeting of the IL-16 prodomain induces a G(0)/G(1) arrest in the cell cycle. Taken together, the high degree of conservation of the prodomain among species, the presence of two PDZ motifs, and the nuclear localization and subsequent inhibitory effect on cell cycle progression suggest that pro-IL-16 is cleaved into two functional proteins, a C-terminal-secreted cytokine and an N-terminal product, which affects the cell cycle.

Animals↗

PubMed2001

Structure-activity relationships within a family of selectively cytotoxic macrolide natural products.

[figure: see text] We describe a semi-synthetic deglycosylated derivative of apoptolidin that retains considerable activity against the mitochondrial ATPase but has greatly reduced cellular cytotoxicity. We also demonstrate that a related antifungal natural product, cytovaricin, inhibits the same molecular target. Structural comparison of these macrolides provides insights into their conserved features that are presumably important for biological activity and identifies promising avenues at the interface of organic synthesis and biosynthesis for the generation of new selective cytotoxic agents.

Anti-Bacterial Agents↗

PubMed2001

Stretch-induced hairpin-coil transitions in designed polynucleotide chains.

The structural property of a poly( dG-dC) or poly( dA-dT) nucleotide is investigated. At low force and room temperatures, the polymer takes on compact hairpin structures. An abrupt transition from hairpin to random coil occurs at certain critical forces, its high cooperativity is related to the unfavorable formation of hairpin and other kinds of looped structures. It is hence necessary to consider the enthalpic effects of single-stranded loops in realistic models of RNA folding. A possible new way to obtain the statistical weights of elementary nucleotide arrangements is by single-macromolecular mechanical measurements on specifically designed polynucleotides.

Base Pairing↗

PubMed2001

Regulation by chemokines of circulating dendritic cell precursors, and the formation of portal tract-associated lymphoid tissue, in a granulomatous liver disease.

We have studied the recruitment and roles of distinct dendritic cell (DC) precursors from the circulation into Propionibacterium acnes-induced granulomas in mouse liver. During infection, F4/80(-)B220(-)CD11c(+) DC precursors appeared in the circulation, migrated into the perisinusoidal space, and matured within newly formed granulomas. Recruited DCs later migrated to the portal area to interact with T cells in what we term "portal tract-associated lymphoid tissue" (PALT). Macrophage inflammatory protein 1alpha attracted blood DC precursors to the sinusoidal granuloma, whereas secondary lymphoid organ chemokine (SLC) attracted mature DCs to the newly identified PALT. Anti-SLC antibody diminished PALT expansion while exacerbating granuloma formation. Therefore, circulating DC precursors can migrate into a solid organ like liver, and participate in the granulomatous reaction in response to specific chemokines.

Animals↗

PubMed2001

Bone mass and the risk of colon cancer among postmenopausal women: the Framingham study.

Although postmenopausal estrogen use has been associated with a lower risk of colon cancer in women, some studies do not confirm such findings. No known study has examined the effect of cumulative estrogen exposure on colon cancer risk. Bone mass has been proposed as a marker of cumulative exposure to endogenous and exogenous estrogens. By using data on 1,394 Massachusetts women in the Framingham Study who underwent hand radiography in 1967-1970, the authors examined the association between bone mass (from relative areas of the second metacarpal) and colon cancer incidence. Over 27 years of follow-up, 44 incident colon cancer cases occurred. Colon cancer incidence decreased from 2.19 per 1,000 person-years among the women in the lowest age-specific tertile of bone mass to 1.59 and 1.08 among women in the middle and the highest tertiles, respectively. After adjustment for age and other potential confounding factors, the rate ratios of colon cancer were 1.0, 0.7 (95% confidence interval: 0.3, 1.3), and 0.4 (95% confidence interval: 0.2, 0.9) from the lowest to the highest tertile (p for trend = 0.033). No association was found between bone mass and rectal cancer. The findings suggest that women with higher bone mass, perhaps reflecting greater cumulative estrogen exposure, have a decreased risk of colon cancer.

Adult↗