To determine whether endothelin-1 (ET-1) induces hypertrophy of cardiomyocytes, the effects ET-1 on expression muscle-specific genes and a proto-oncogene, c-fos, in cultured neonatal rat cardiomyocytes were examined by Northern blot analysis. (10(-7) M) induced about twofold to fourfold increases gene myosin light chain 2, alpha-actin, troponin I after 6 hours, which continued up 24 hours. The ET-1-induced mRNA levels for these dose dependent (10(-9) 10(-7) M). Run-on transcriptional assay...

BACKGROUND Cardiac hypertrophy is commonly observed in acromegalic patients, whom serum insulin-like growth factor-I (IGF-I) levels are elevated. In the present study, we examined whether IGF-I induces cultured neonatal rat cardiomyocytes through its specific receptor and IGF binding protein-3 (IGFBP-3), which a major circulating carrier protein for IGF-I, inhibits IGF-I-induced cardiac vitro. METHODS AND RESULTS Because response of characterized by induction expression muscle-specific...

BACKGROUND We have recently shown that angiotensin II-induced hypertrophy of cultured rat cardiomyocytes was partially blocked by an endothelin (ET) receptor antagonist (BQ123) selective for the ETA subtype, suggesting possible involvement endogenous ET-1 in mechanism cardiac vitro. In present study, we studied vivo blockade effects BQ123 on provoked left ventricular overload with aortic banding adult rats. METHODS AND RESULTS Forty rats were divided into four groups: (1) sham-operated...

This multicenter, phase III study compared overall survival (OS) of second-line pemetrexed plus best supportive care (BSC) versus BSC alone in patients with advanced malignant pleural mesothelioma (MPM). Secondary end points included response rate, progression-free (PFS), time to tumor progression (TTP), treatment failure (TTF), and toxicity.Patients relapsed MPM after first-line chemotherapy were randomly assigned receive 500 mg/m(2) (P+BSC) every 21 days or alone.The enrolled 243 (123 on...

Summary Cellular senescence is an important phenomenon in decreased cellular function. Recently, it was shown that induced proliferating cells within a short period of time by oxidative stresses. This known as premature senescence. However, still unknown whether can be also cardiomyocytes. The aim the present study to investigate senescence‐like phenotype cardiomyocytes stress. In obtained from aged rats (24 months age), staining for senescence‐associated β‐galactosidase increased...

We report here that the expression of virtually all proposed c-Myc target genes is unchanged in cells containing a homozygous null deletion c- myc . Two noteworthy exceptions are gene cad , which has reduced log phase and serum induction cells, growth arrest gadd45 derepressed by knockout. Thus, only targets may contribute to dramatic slow phenotype cells. Our results demonstrate loss-of-function approach critical for evaluation potential genes.

Mammalian cardiomyocytes irreversibly lose their capacity to proliferate soon after birth, yet the underlying mechanisms have been unclear. Cyclin D1 and its partner, cyclin-dependent kinase 4 (CDK4), are important for promoting G1-to-S phase progression via phosphorylation of retinoblastoma (Rb) protein. Mitogenic stimulation induces hypertrophic cell growth upregulates expression cyclin in postmitotic cardiomyocytes. In present study, we show that, neonatal rat cardiomyocytes, D-type...

Endothelin-1 (ET-1), a 21-amino acid vasoconstrictive peptide, increases intracellular Ca2+ level and has hypertrophic action on ventricular myocytes. To elucidate possible role of entry through sarcolemmal channels this ET-1 action, we examined effects L-type (ICa,L) T-type (ICa,T) currents in cultured neonatal rat myocytes using the patch-clamp technique. at concentration 10 nM increased maximum current density ICa,T from -3.0 +/- 1.4 microA/cm2 control condition to -4.4 1.6 (p < 0.01)....

Abstract Purpose: The objective of this study was to evaluate the efficacy and safety two doses pemetrexed supplemented with folic acid vitamin B12 in pretreated Japanese patients advanced non-small cell lung cancer (NSCLC). Experimental Design: Patients an Eastern Cooperative Oncology Group performance status 0 2, stage III or IV, who received previously one chemotherapy regimens were randomized receive 500 mg/m2 (P500) 1,000 (P1000) on day 1 every 3 weeks. primary endpoint response rate....

Lipid composition of liver and some other tissues was determined in seven cases "foam cell syndrome" which induced by the administration 4, 4′-diethylamino-ethoxyhexestrol dihydrochloride. Free cholesterol total phospholipids were increased liver. Phospholipid analysis showed marked increases lysobisphos-phatidic acid phosphatidylinositol An increase lysobisphosphatidic also detected spleen, muscle, lymph nodes urinary sediment. However, this phospholipid not leucocytes. Accumulation...

Transcriptional activation by c-Myc through specific E box elements is thought to be essential for its biological role. However, c-MycS unable activate transcription these and yet retains the ability stimulate proliferation, induce anchorage-independent growth, apoptosis. In addition, repress of several promoters. Furthermore, can rescue c- myc null phenotype in fibroblasts with homozygous deletion . Taken together, our data argue against paradigm that all functions are mediated...

Abstract —Cardiomyocytes are terminally differentiated cells characterized as withdrawal cell-cycle machinery, but nonetheless they known to express regulators. Because many proteins related the cell cycle induce apoptosis in proliferating cells, we examined involvement of these pathway cardiomyocytes. Primary rat cardiomyocytes were exposed a severe hypoxic condition apoptosis. The rate increased ≈40% under 24 hours hypoxia evaluated by TUNEL method. cyclin A protein level assessed...

Lactobacillus kefiranofaciens sp. nov. is described. Four strains of this species isolated from kefir grains are slime-forming, homofermentative, rod-shaped lactic acid bacteria. They differ all the validly described homofermentative genus in their carbohydrate fermentation pattern. Their guanine-plus-cytosine content deoxyribonucleic 34 to 35 mol%. Deoxyribonucleic acids obtained six other do not show significant relatedness a representative strain new species. The type L. WT-2B (ATCC 43761).

The c-myc proto-oncogene encodes a transcription factor that participates in the regulation of cellular proliferation, differentiation, and apoptosis. Ectopic overexpression c-Myc has been shown to sensitize cells We report here lacking activity due disruption gene by targeted homologous recombination are defective DNA damage-initiated apoptosis G2 phase cell cycle. downstream effector is cyclin A, whose ectopic expression c-myc−/− rescues defect. kinetics response indicate induction A...

Hepatocyte growth factor (HGF) plays a role in cell protection, antiapoptosis, antifibrosis, and angiogenesis. However, the of HGF immune system is not well defined. We examined influence on T cells effects therapy acute myocarditis. Lewis rats were immunized day 0 with cardiac myosin to establish experimental autoimmune myocarditis (EAM). Human gene hemagglutinating virus Japan-envelope vector was injected directly into myocardium or 14 (two groups treated rats). Rats killed 21. Expression...