The six-minute walk test is a submaximal exercise that can be performed even by patient with heart failure not tolerating maximal testing. To elucidate the clinical significance and prognostic value of in patients primary pulmonary hypertension (PPH), we sought (1) to assess relation between distance walked during capacity determined cardiopulmonary testing, (2) investigate comparison other noninvasive parameters. was 43 PPH, together echocardiography, right catheterization, measurement...

In the majority of cervical cancers, DNAs high-risk mucosotpropic human papillomaviruses (HPVs), such as type 16, are maintained so to express two viral proteins, E6 and E7, suggesting an essential importance carcinogenesis. The HPV proteins known inactivate p53 tumor suppressor protein but appear have additional, molecularly unknown function(s). this study, we demonstrate that these can bind second PDZ domain homologue Drosophila discs large (hDLG) through their C-terminal XS/TXV/L (where X...

Histone H3 (H3) phosphorylation at Ser(10) occurs during mitosis in eukaryotes and was recently shown to play an important role chromosome condensation Tetrahymena. When producing monoclonal antibodies that recognize glial fibrillary acidic protein Thr(7), we obtained some cross-reacted with early mitotic chromosomes. They reacted 15-kDa phosphoprotein specifically cell lysate. With microsequencing, this proved be H3. Mutational analysis revealed they recognized Ser(28) phosphorylation. Then...

Curcumin is a polyphenol that commonly used for its perceived health benefits. However, the absorption efficacy of curcumin too low to exhibit beneficial effects. We have successfully developed highly absorptive dispersed with colloidal nano-particles, and named it THERACURMIN. The THERACURMIN was investigated compared powder. area under blood concentration–time curve (AUC) after oral administration found be more than 40-fold higher powder in rats. Then, healthy human volunteers were...

Hemodynamic overload in the heart can trigger maladaptive hypertrophy of cardiomyocytes. A key signaling event this process is nuclear acetylation by histone deacetylases and p300, an intrinsic acetyltransferase (HAT). It has been previously shown that curcumin, a polyphenol responsible for yellow color spice turmeric, possesses HAT inhibitory activity with specificity p300/CREB-binding protein. We found curcumin inhibited hypertrophy-induced DNA-binding abilities GATA4,...

Enhanced coronary vasomotion may contribute to acute occlusion during the phase of myocardial infarction (AMI). Japanese have a higher incidence variant angina than Caucasian patients, but racial differences in vasomotor reactivity early after AMI are controversial.The same team studied 15 and 19 patients within 14 days by acetylcholine injection into non-infarct-related (NIRA) infarct-related (IRA) arteries followed nitroglycerin. Incidence vasodilation, vasoconstriction, spasm, basal tone...

The E6 protein of cervical cancer-associated human papillomaviruses (HPVs) is known to suppress keratinocyte differentiation through unidentified mechanisms. Notch1 a determinant and functions as tumor suppressor in mammalian epidermis. Here, we report that the gene novel target p53 can be down-regulated by degradation normal epithelial cells. Thus, inactivation or short-hairpin RNA (shRNA) resulted reduced expression at transcription level, p53-responsive element could identified promoter....

When exposed to genotoxic stress, eukaryotic cells demonstrate a DNA damage response with delay or arrest of cell-cycle progression, providing time for repair. Induction the Epstein-Barr virus (EBV) lytic program elicited cellular response, activation ataxia telangiectasia-mutated (ATM) signal transduction pathway. Activation ATM-Rad3-related (ATR) replication checkpoint pathway, in contrast, was minimal. The sensor Mre11-Rad50-Nbs1 (MRN) complex and phosphorylated ATM were recruited...

The effect of preexistent coronary collateral perfusion on the prevention left ventricular aneurysm formation was examined in 47 patients undergoing an intracoronary thrombolysis within 6 hours after onset a first acute anterior myocardial infarction. Left and wall motion were analyzed with cineventriculography. A determined as well-defined demarcation infarcted segment from normally contracting myocardium. In 25 successful (group A), observed one patient (4%) during chronic stage 10 who had...

The current concept regarding cell cycle regulation of DNA replication is that Cdt1, together with origin recognition complex and CDC6 proteins, constitutes the machinery loads minichromosome maintenance complex, a candidate replicative helicase, onto chromatin during G(1) phase. actions are suppressed through phosphorylation by cyclin-dependent kinases (Cdks) after S phase to prohibit rereplication. It has been suggested in metazoan cells function Cdt1 blocked binding an inhibitor protein,...

Background Collateral growth is induced by chemical signals from the ischemic myocardium. We hypothesized that angiogenic factors are produced cardiac tissue; they diffusible, more concentrated in pericardial fluids, and increased myocardial ischemia. Methods Results With use of an enzyme-linked immunosorbent assay, we measured concentrations basic fibroblast factor (bFGF) vascular endothelial (VEGF) fluids 12 patients with unstable angina (group 1) 8 nonischemic heart diseases 2). The...

Eukaryotic cells are equipped with machinery to monitor and repair damaged DNA. Herpes simplex virus (HSV) DNA replication occurs at discrete sites in nuclei, the compartment, where viral proteins cluster synthesize a large amount of In present study, HSV infection was found elicit cellular damage response, activation ataxia-telangiectasia-mutated (ATM) signal transduction pathway, as observed by autophosphorylation ATM phosphorylation multiple downstream targets including Nbs1, Chk2, p53,...

The purpose of the present study was to evaluate potential diurnal changes in resting coronary blood flow under conditions comparable myocardial oxygen requirements. We studied 21 conscious, dogs instrumented for measurement flow, left ventricular pressure, and regional segment length. Recordings were taken early morning late afternoon. In afternoon, circumflex 12.8% higher than morning, without detectable major hemodynamic determinants consumption, i.e., heart rate, peak positive dP/dt,...

The activity of human Cdt1 is negatively regulated by multiple mechanisms. This suggests that deregulation may have a deleterious effect. Indeed, it has been suggested overexpression can induce rereplication in cancer cells and activates Ataxia-telangiectasia-mutated (ATM) kinase and/or ATM- Rad3-related (ATR) kinase-dependent checkpoint pathways. In this report, we highlight new interesting aspect deregulation: data from several different systems all strongly indicate unregulated at...

In eukaryotic cells, replication of genomic DNA initiates from multiple origins distributed on chromosomes. To ensure that each origin is activated precisely only once during S phase, a system has evolved which features periodic assembly and disassembly essential pre-replication complexes (pre-RCs) at origins. The pre-RC reaction involves the loading presumptive replicative helicase, MCM2-7 complexes, onto chromatin by recognition complex (ORC) two factors, CDC6 Cdt1. cell cycle driven...

Ovarian surface epithelium (OSE) is considered to give rise epithelial ovarian carcinomas (EOCs). To elucidate early processes contributing the development of EOCs from OSE, two batches primary human OSE cells were transduced with non-viral genes (mutant Cdk4 , cyclinD1 and hTERT ) so as efficiently establish normal diploid without chromosomal instability. Then defined genetic alterations frequently observed in into cells. A combination p53 inactivation oncogenic K ras transduction did not...

The aims of this study were: (1) to show the feasibility using adipose-derived stromal vascular fraction (SVF) as an alternative bone marrow mono nuclear cell (BM-MNC) for transplantation into chronic ischemic myocardium; and (2) explore underlying mechanisms with focus on anti-inflammation role engrafted SVF BM-MNC post myocardial infarction (MI) against left ventricular (LV) remodelling cardiac dysfunction. Four weeks after anterior descending coronary artery ligation, 32 Male Lewis rats...

Background: A natural p300-specific histone acetyltransferase (HAT) inhibitor, curcumin, may have therapeutic potential for heart failure. However, it is unclear whether curcumin exhibits beneficial additive or synergistic effects on conventional therapy with angiotensin-converting enzyme inhibitors (ACEIs). Methods and Results: Rats were subjected to a sham operation left coronary artery ligation. One week later, 34 rats moderate sized myocardial infarction (MI) randomly assigned 4 groups:...