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The type Ia supernova SNLS-03D3bb from a super-Chandrasekhar-mass white dwarf star.

Howell D Andrew , Sullivan Mark , Nugent Peter E , Ellis Richard S , Conley Alexander J , Le Borgne Damien , Carlberg Raymond G , Guy Julien , Balam David , Basa Stephane , Fouchez Dominique , Hook Isobel M , Hsiao Eric Y , Neill James D , Pain Reynald , Perrett Kathryn M , Pritchet Christopher J
Nature.2006 Sep 21 ; 443(7109):308-11.
PMID: 16988705[]

先週： 1位 95view,1users 保存 要約 閉じる

The accelerating expansion of the Universe, and the need for dark energy, were inferred from observations of type Ia supernovae. There is a consensus that type Ia supernovae are thermonuclear explosions that destroy carbon-oxygen white dwarf stars that have accreted matter from a companion star, although the nature of this companion remains uncertain. These supernovae are thought to be reliable distance indicators because they have a standard amount of fuel and a uniform trigger: they are predicted to explode when the mass of the white dwarf nears the Chandrasekhar mass of 1.4 solar masses (M(o)). Here we show that the high-redshift supernova SNLS-03D3bb has an exceptionally high luminosity and low kinetic energy that both imply a super-Chandrasekhar-mass progenitor. Super-Chandrasekhar-mass supernovae should occur preferentially in a young stellar population, so this may provide an explanation for the observed trend that overluminous type Ia supernovae occur only in 'young' environments. As this supernova does not obey the relations that allow type Ia supernovae to be calibrated as standard candles, and as no counterparts have been found at low redshift, future cosmology studies will have to consider possible contamination from such events.

2',5,7-Trihydroxy-4',5'-(2,2-dimethylchromeno)-8-(3-hydroxy-3-methylbutyl) flavanone purified from Cudrania tricuspidata induces apoptotic cell death of human leukemia U937 cells.

Rho Yoon-Hwa , Yoon Soo-Hyun , Kim Eun-Kyung , Kang Ji-Young , Lee Byong-Won , Park Ki-Hun , Bae Young-Seuk
Nat Prod Res.2007 Jun ; 21(7):616-24.
PMID: 17613819[]

先週： 2位 73view,0users 保存 要約 閉じる

Cellular DNA topoisomerase I is an important target in cancer chemotherapy. A chloroform extract of the root barks of Cudrania tricuspidata showed an inhibitory effect on mammalian DNA topoisomerase I. The topoisomerase I inhibitory compound was purified and identified as 2',5,7-trihydroxy-4',5'-(2,2-dimethylchromeno)-8-(3-hydroxy-3-methylbutyl) flavanone. The compound, temporarily designated as PKH-3, was shown to inhibit the activity of topoisomerase I with IC50 about 1.0 mM. Concentration of 10 microM PKH-3 caused 50% growth inhibition of human cancer cell U937. PKH-3-induced cell death was characterized with the cleavage of poly(ADP-ribose) polymerase (PARP) and pro-caspase 3. Furthermore, PKH-3 induced the fragmentation of DNA into multiples of 180 b.p. (an apoptotic DNA ladder), indicating that the inhibitor triggered apoptosis. This induction of apoptosis by PKH-3 was also confirmed using flow cytometry analysis. Taken together, these results suggest that PKH-3 may function by inhibiting oncogenic disease, at least in part, through the inhibition of topoisomerase I activity.

Effects of olmesartan, an angiotensin II receptor blocker, and amlodipine, a calcium channel blocker, on Cardio-Ankle Vascular Index (CAVI) in type 2 diabetic patients with hypertension.

Miyashita Yoh , Saiki Atsuhito , Endo Kei , Ban Noriko , Yamaguchi Takashi , Kawana Hidetoshi , Nagayama Daiji , Ohira Masahiro , Oyama Tomokazu , Shirai Kohji
J Atheroscler Thromb.2009 Oct ; 16(5):621-6.
PMID: 19907103[]

先週： 4位 48view,4users 保存 要約 閉じる

AIM: Recently, a novel device for measuring the cardio-ankle vascular index (CAVI) as an arterial stiffness parameter has been developed. In this study, we evaluated the effect of angiotensin II receptor blocker (ARB) and calcium channel (Ca) blocker on CAVI in type 2 diabetic patients with hypertension.METHODS: Seventy type 2 diabetes mellitus patients with hypertension were enrolled and randomly divided into two groups. One group was administered olmesartan medoxomil 10 mg/day for 12 months (ARB group), and the other group was administered amlodipine besilate 5 mg/day for 12 months (Ca blocker group).RESULTS: In the ARB group, a significant decrease in CAVI was observed after 12 months; however, no significant change in CAVI was observed in the Ca blocker group although changes in blood pressure were almost the same. By simple regression analyses, CAVI changes correlated positively with 8-OHdG changes.CONCLUSIONS: Olmesartan, an ARB, improved arterial stiffness more than amlodipine, and this effect might be due to not only the blood pressure-lowering effect but also to reducing the potential of oxidative stress recognized in olmesartan.

A novel GSK-3beta inhibitor reduces Alzheimer's pathology and rescues neuronal loss in vivo.

Serenó L , Coma M , Rodríguez M , Sánchez-Ferrer P , Sánchez M B , Gich I , Agulló J M , Pérez M , Avila J , Guardia-Laguarta C , Clarimón J , Lleó A , Gómez-Isla T
Neurobiol Dis.2009 Sep ; 35(3):359-67.
PMID: 19523516[]

先週： 5位 39view,2users 保存 要約 閉じる

Amyloid deposits, neurofibrillary tangles, and neuronal cell death in selectively vulnerable brain regions are the chief hallmarks in Alzheimer's (AD) brains. Glycogen synthase kinase-3 (GSK-3) is one of the key kinases required for AD-type abnormal hyperphosphorylation of tau, which is believed to be a critical event in neurofibrillary tangle formation. GSK-3 has also been recently implicated in amyloid precursor protein (APP) processing/Abeta production, apoptotic cell death, and learning and memory. Thus, GSK-3 inhibition represents a very attractive drug target in AD and other neurodegenerative disorders. To investigate whether GSK-3 inhibition can reduce amyloid and tau pathologies, neuronal cell death and memory deficits in vivo, double transgenic mice coexpressing human mutant APP and tau were treated with a novel non-ATP competitive GSK-3beta inhibitor, NP12. Treatment with this thiadiazolidinone compound resulted in lower levels of tau phosphorylation, decreased amyloid deposition and plaque-associated astrocytic proliferation, protection of neurons in the entorhinal cortex and CA1 hippocampal subfield against cell death, and prevention of memory deficits in this transgenic mouse model. These results show that this novel GSK-3 inhibitor has a dual impact on amyloid and tau alterations and, perhaps even more important, on neuronal survival in vivo further suggesting that GSK-3 is a relevant therapeutic target in AD.

RORgamma-expressing Th17 cells induce murine chronic intestinal inflammation via redundant effects of IL-17A and IL-17F.

Leppkes Moritz , Becker Christoph , Ivanov Ivaylo I , Hirth Sebastian , Wirtz Stefan , Neufert Clemens , Pouly Sandrine , Murphy Andrew J , Valenzuela David M , Yancopoulos George D , Becher Burkhard , Littman Dan R , Neurath Markus F
Gastroenterology.2009 Jan ; 136(1):257-67.
PMID: 18992745[]

先週： 6位 38view,2users 保存 要約 閉じる

BACKGROUND AND AIMS: IL-17-producing CD4(+) T-helper cells (Th17) contribute to chronic autoimmune inflammation in the brain, and levels of Th17-derived cytokines increase in patients with colitis, suggesting a role in pathogenesis. We analyzed the roles of Th17 cells and the transcription factor retinoic acid receptor-related organ receptor (ROR)gamma, which regulates Th17 differentiation, in chronic intestinal inflammation. METHODS: Using an adoptive transfer model of colitis, we compared the colitogenic potential of wild-type, interleukin-17A (IL-17A)-, IL-17F-, IL-22-, and RORgamma-deficient CD4(+)CD25(-) T cells in RAG1-null mice. RESULTS: Adoptive transfer of IL-17A-, IL-17F-, or IL-22-deficient T lymphocytes into RAG1-null mice caused severe colitis that was indistinguishable from that caused by wild-type cells. In contrast, transfer of RORgamma-null T cells failed to increase mucosal IL-17 cytokine levels and did not induce colitis. Treatment with IL-17A was able to restore colitis after transfer of RORgamma-null T cells, indicating a crucial role for Th17 cells in pathogenesis. Treatment of RAG1 mice that received IL-17F-null (but not wild-type) T cells with a neutralizing anti-IL-17A antibody significantly suppressed disease, indicating redundant biological effects of IL-17A and IL-17F. CONCLUSIONS: We have identified a crucial role of RORgamma-expressing Th17 cells in chronic intestinal inflammation. RORgamma controls IL-17A and IL-17F production, and these cytokines have a redundant but highly pathogenic role in gut inflammation. Reagents that target RORgamma or a combination of anti-IL-17A and anti-IL-17F might be developed as therapeutics for chronic colitis.

A randomized, double-blind, four-arm parallel-group study of the efficacy and safety of azelnidipine and olmesartan medoxomil combination therapy compared with each monotherapy in Japanese patients with essential hypertension: the REZALT study.

Hypertens Res.2009 Oct 9 ; ():.
PMID: 19816505[]

先週： 9位 32view,25users 保存 要約 閉じる

A 12-week randomized, double-blind, four-arm parallel-group, comparative study was conducted in patients with essential hypertension to evaluate the antihypertensive effect and safety of combination therapy with olmesartan medoxomil (OLM, an angiotensin-receptor blocker) 20 mg plus azelnidipine (AZL, a long-acting dihydropyridine calcium channel blocker) 16 mg, (O/A (20/16)), or OLM 10 mg/AZL 8 mg (O/A (10/8)) compared with those of monotherapy with OLM 20 mg (OLM (20)) or AZL 16 mg (AZL (16)). The change from baseline to week 12 in seated blood pressure (SeBP) was -23.6/-14.2 mm Hg (systolic/diastolic BP) in the O/A (20/16) group, and -20.3/-13.0 mm Hg in the O/A (10/8) group, which was a significantly greater reduction in SeBP than in the monotherapy groups (-15.7/-9.9 mm Hg in OLM (20); -15.0/-9.4 mm Hg in AZL (16)). The change from baseline in 24-h ambulatory BP was also significantly greater in the O/A (20/16) and O/A (10/8) combination groups (-22.1/-13.5 and -18.2/-10.6 mm Hg, respectively) than in the OLM (20) and AZL (16) monotherapy groups (-12.1/-6.9 and -12.0/-6.9 mm Hg). The proportion of patients achieving the SeBP goal (<130/85 mm Hg for normal BP or <140/90 mm Hg for high-normal BP) was significantly higher in the O/A (20/16) combination group than in the monotherapy groups. The incidence of adverse events was similar in the O/A combination groups and the monotherapy groups. These results showed that combination therapy with O/A was well tolerated and exerted a stronger antihypertensive effect compared with monotherapy with OLM or AZL in patients with essential hypertension.Hypertension Research advance online publication, 9 October 2009; doi:10.1038/hr.2009.163.

Adult satellite cells and embryonic muscle progenitors have distinct genetic requirements.

Lepper Christoph , Conway Simon J , Fan Chen-Ming
Nature.2009 Jul 30 ; 460(7255):627-31.
PMID: 19554048[]

先週： 3位 30view,6users 保存 要約 閉じる

Myogenic potential, survival and expansion of mammalian muscle progenitors depend on the myogenic determinants Pax3 and Pax7 embryonically, and Pax7 alone perinatally. Several in vitro studies support the critical role of Pax7 in these functions of adult muscle stem cells (satellite cells), but a formal demonstration has been lacking in vivo. Here we show, through the application of inducible Cre/loxP lineage tracing and conditional gene inactivation to the tibialis anterior muscle regeneration paradigm, that, unexpectedly, when Pax7 is inactivated in adult mice, mutant satellite cells are not compromised in muscle regeneration, they can proliferate and reoccupy the sublaminal satellite niche, and they are able to support further regenerative processes. Dual adult inactivation of Pax3 and Pax7 also results in normal muscle regeneration. Multiple time points of gene inactivation reveal that Pax7 is only required up to the juvenile period when progenitor cells make the transition into quiescence. Furthermore, we demonstrate a cell-intrinsic difference between neonatal progenitor and adult satellite cells in their Pax7-dependency. Our finding of an age-dependent change in the genetic requirement for muscle stem cells cautions against inferring adult stem-cell biology from embryonic studies, and has direct implications for the use of stem cells from hosts of different ages in transplantation-based therapy.

IL-17A versus IL-17F induced intracellular signal transduction pathways and modulation by IL-17RA and IL-17RC RNA interference in AGS gastric adenocarcinoma cells.

Zhou Yuan , Toh Myew-Ling , Zrioual Saloua , Miossec Pierre
Cytokine.2007 Jun ; 38(3):157-64.
PMID: 17644350[]

先週： 7位 29view,3users 保存 要約 閉じる

Inflammatory processes are implicated in gastric cancer development. In contrast, the role of inflammation and proinflammatory cytokines in established cancer remains to be clarified. We investigated the contribution of IL-17A versus IL-17F-mediated intracellular signalling pathways in human gastric adenocarcinoma AGS cells. IL-8 secretion was evaluated by ELISA, mitogen-activated protein kinase (MAPK)(4) by Western blotting, and activator protein 1(AP-1) and nuclear factor kappa B (NFkappaB) by TransAM transcription factor assay or qRT-PCR. IL-17RA and IL-17RC inhibition were achieved by small interfering RNA (siRNA). IL-17A significantly induced activation of all three MAPK (ERK, p38 and JNK) and downstream transcription factors AP-1 and p65 NFkappaB. IL-17F was less potent but induced a significant activation of p65 NFkappaB. Consistently, IL-17A was more potent to induce IL-8 secretion than IL-17F. Inhibition of either IL-17RA or IL-17RC expression via siRNA led to near complete abrogation of IL-17A-mediated c-Jun and p65 activation. These data suggest that in gastric cancer, absence of either IL-17RA or IL-17RC can inhibit IL-17 responsiveness. Conversely, downstream of IL-17R binding, IL-17A and IL-17F induce key signal transduction pathways implicated in inflammation and carcinogenesis. IL-17A, and possibly IL-17F, may contribute to amplification and persistence of inflammatory processes implicated in inflammation-associated cancer.

Impact of Olmesartan on Progression of Coronary Atherosclerosis A Serial Volumetric Intravascular Ultrasound Analysis From the OLIVUS (Impact of OLmesarten on progression of coronary atherosclerosis: evaluation by IntraVascular UltraSound) Trial.

Hirohata Atsushi , Yamamoto Keizo , Miyoshi Toru , Hatanaka Kunihiko , Hirohata Satoshi , Yamawaki Hitoshi , Komatsubara Issei , Murakami Masaaki , Hirose Eiki , Sato Shinji , Ohkawa Keisuke , Ishizawa Makoto , Yamaji Hirosuke , Kawamura Hiroshi , Kusachi Shozo , Murakami Takashi , Hina Kazuyoshi , Ohe Tohru
J Am Coll Cardiol.2010 Mar 9 ; 55(10):976-982.
PMID: 20202514[]

29view,1users 保存 要約 閉じる

OBJECTIVES: The aim of this study was to evaluate the impact of olmesartan on progression of coronary atherosclerosis. BACKGROUND: Prior intravascular ultrasound (IVUS) trial results suggest slowing of coronary atheroma progression with some medicines but have not shown convincing evidence of regression with angiotension-II receptor blocking agents. METHODS: A prospective, randomized, multicenter trial-OLIVUS (Impact of OLmesartan on progression of coronary atherosclerosis: evaluation by IntraVascular UltraSound)-was performed in 247 stable angina pectoris patients with native coronary artery disease. When these patients underwent percutaneous coronary intervention for culprit lesions, IVUS was performed in their nonculprit vessels (without angiographically documented coronary stenosis [<50%]). Patients were randomly assigned to receive 10 to 40 mg of olmesartan or control and treated with a combination of beta-blockers, calcium channel blockers, diuretics, nitrates, glycemic control agents, and/or statins per physician's guidance. Serial IVUS examinations (baseline and 14-month follow-up) were performed to assess coronary atheroma volume. Volumetric IVUS analyses included lumen, plaque, vessel volume, percent atheroma volume (PAV), percent change in total atheroma volume (TAV) and PAV. RESULTS: Patient characteristics and blood pressure control were identical between the 2 groups. However, follow-up IVUS showed significantly decreased TAV and percent change in PAV in the olmesartan group (5.4% vs. 0.6 % for TAV and 3.1% vs. -0.7% for percent change in PAV, control vs. olmesartan, p < 0.05 for all). CONCLUSIONS: These observations suggest a positive role in a potentially lower rate of coronary atheroma progression through the administration of olmesartan, an angiotension-II receptor blocking agent, for patients with stable angina pectoris.

Effect of valsartan or olmesartan addition to amlodipine on ankle edema in hypertensive patients.

Fogari Roberto , Malamani Gian , Corradi Luca , Mugellini Amedeo , Preti Paola , Zoppi Annalisa , Derosa Giuseppe
Adv Ther.2010 Feb 19 ; ():.
PMID: 20174905[]

先週： 8位 26view,3users 保存 要約 閉じる

INTRODUCTION: The objective of this study was to compare the effect on ankle edema of adding valsartan (V) or olmesartan (O) to amlodipine (A) in the treatment of hypertension. METHODS: After a 4-week placebo period, 74 adult outpatients with essential hypertension (diastolic blood pressure [DBP] >90 and <110 mmHg, and systolic blood pressure [SBP] >140 mmHg) were treated with A 10 mg once daily for 4 weeks. Thereafter, nonresponder patients (DBP >90 mmHg and/or SBP >140 mmHg; n=51) were randomized to receive additional V 160 mg once daily or O 20 mg once daily for 8 weeks in two crossover periods, each separated by a 4-week placebo period. Clinic blood pressure (BP), heart rate, and ankle/foot volume (AFV) were evaluated and blood samples were drawn to evaluate plasma norepinephrine (NE) levels. RESULTS: Both V/A and O/A induced a greater SBP/DBP reduction than A monotherapy (-26.4/-20.8 mmHg and -24.4/-19.1 mmHg, respectively; all P<0.001 vs. baseline and P<0.01 vs. A). A monotherapy increased AFV by 24%, P<0.001 vs. baseline, while the addition of either V or A reduced such increases. However, with V/A the AFV increase (+9.7%, P<0.05 vs. baseline, P<0.01 vs. A) was lower than with O/A (+16.7%, P<0.01 vs. baseline, P<0.05 vs. A); the difference between the two combinations was significant. Plasma NE levels were significantly increased by A (+44.6%) and values did not change with the addition of V (+35.2%) or O (+33.7%). Plasma active renin (PAR) was unchanged by A but increased by V/A (+214.4%, P<0.05 vs. baseline) and further by O/A (+325.6%, P<0.01 vs. baseline; difference between the 2 combinations: P<0.05). An inverse correlation was found between the AFV decrease and PAR increase (r=-0.31, P<0.05). CONCLUSION: Adding V or O to A reduced ankle edema, but this effect was more pronounced with V. The greater degree of renin-angiotensin system activation observed with Ocould be related to such a difference.

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週間人気論文ランキング - 保存数 (2010/03/13/ 09時更新)

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A randomized, double-blind, four-arm parallel-group study of the efficacy and safety of azelnidipine and olmesartan medoxomil combination therapy compared with each monotherapy in Japanese patients with essential hypertension: the REZALT study.

Hypertens Res.2009 Oct 9 ; ():.
PMID: 19816505[]

先週： 1位 32view,25users 保存 要約 閉じる

A 12-week randomized, double-blind, four-arm parallel-group, comparative study was conducted in patients with essential hypertension to evaluate the antihypertensive effect and safety of combination therapy with olmesartan medoxomil (OLM, an angiotensin-receptor blocker) 20 mg plus azelnidipine (AZL, a long-acting dihydropyridine calcium channel blocker) 16 mg, (O/A (20/16)), or OLM 10 mg/AZL 8 mg (O/A (10/8)) compared with those of monotherapy with OLM 20 mg (OLM (20)) or AZL 16 mg (AZL (16)). The change from baseline to week 12 in seated blood pressure (SeBP) was -23.6/-14.2 mm Hg (systolic/diastolic BP) in the O/A (20/16) group, and -20.3/-13.0 mm Hg in the O/A (10/8) group, which was a significantly greater reduction in SeBP than in the monotherapy groups (-15.7/-9.9 mm Hg in OLM (20); -15.0/-9.4 mm Hg in AZL (16)). The change from baseline in 24-h ambulatory BP was also significantly greater in the O/A (20/16) and O/A (10/8) combination groups (-22.1/-13.5 and -18.2/-10.6 mm Hg, respectively) than in the OLM (20) and AZL (16) monotherapy groups (-12.1/-6.9 and -12.0/-6.9 mm Hg). The proportion of patients achieving the SeBP goal (<130/85 mm Hg for normal BP or <140/90 mm Hg for high-normal BP) was significantly higher in the O/A (20/16) combination group than in the monotherapy groups. The incidence of adverse events was similar in the O/A combination groups and the monotherapy groups. These results showed that combination therapy with O/A was well tolerated and exerted a stronger antihypertensive effect compared with monotherapy with OLM or AZL in patients with essential hypertension.Hypertension Research advance online publication, 9 October 2009; doi:10.1038/hr.2009.163.

Comparison of the long-term effects of candesartan and olmesartan on plasma angiotensin II and left ventricular mass index in patients with hypertension.

Hypertens Res.2009 Nov 20 ; ():.
PMID: 19927151[]

先週： 2位 17view,10users 保存 要約 閉じる

In general, treatment with most angiotensin receptor blockers (ARBs) increases plasma angiotensin II (Ang II) level because of a lack of negative feedback on renin activity. Olmesartan is a potential ARB inducing activation of angiotensin-converting enzyme 2 (ACE2) that hydrolyzes Ang II to Ang 1-7, and has shown a beneficial effect on ventricular remodeling. Indeed, a previous study reported that olmesartan treatment resulted in decreased plasma levels of Ang II and aldosterone. However, there has not yet been a study showing the relationship of chronic effects of olmesartan on Ang II and the left ventricular mass index (LVMI) in comparison with those of other ARB.A total of 50 stable outpatients with essential hypertension who had received candesartan for more than 1 year were randomized into two groups: control group (n=25): continuous candesartan treatment at a stable dose; and olmesartan group (n=25): candesartan (8 mg day(-1)) was changed to olmesartan given at a dose of 20 mg day(-1). There was no difference in the baseline characteristics between the two groups. In the control group, there were no significant changes in blood pressure, LVMI or biomarkers during 12 months of study. In the olmesartan group, blood pressure did not change and plasma levels of Ang II decreased during 12 months of study, whereas LVMI was significantly decreased after 12 months (135+/-36 vs. 123+/-29 g m(-2); P<0.01).These findings indicate that replacing candesartan with olmesartan decreased LVMI in association with a sustained decrease of plasma Ang II over a 12-month period without changing blood pressure or plasma aldosterone in patients with essential hypertension.Hypertension Research advance online publication, 20 November 2009; doi:10.1038/hr.2009.192.

The differentiation of rat adipose-derived stem cells into OEC-like cells on collagen scaffolds by co-culturing with OECs.

Wang Bin , Han Jin , Gao Yuan , Xiao Zhifeng , Chen Bing , Wang Xia , Zhao Wenxue , Dai Jianwu
Neurosci Lett.2007 Jun 29 ; 421(3):191-6.
PMID: 17574753[]

先週： 3位 11view,10users 保存 要約 閉じる

Olfactory ensheathing cells (OECs) transplantation is a promising or potential therapy for spinal cord injury (SCI). However, their clinical use is limited because of the availability. Adipose-derived stem cells (ADSCs) have been identified as an alternative source of adult stem cells in recent years. ADSCs could be differentiated into various mesenchymal tissues cells such as chondrocytes, adipocytes, osteoblasts, and myocytes and also could be differentiated into neural lineages. In this study, we examined the feasibility of using ADSCs as a source of stem cells for the differentiation of OECs by co-culture approach. When co-cultured with OECs, the ADSCs on three-dimensional collagen scaffolds were differentiated into OEC-like cells, with similar morphology and antigenic phenotypes (p75NTR+/Nestin+/GFAP-) of OECs. Co-cultured ADSCs were positive for several important functional markers of mature OECs such as neurotrophic factor GDNF, BDNF and myelin protein PLP and the conditioned medium of OEC-like cells could significantly promote DRG neuron growth and axon sprouting without NGF supporting in contrast to that of the ADSCs. Our results showed that ADSCs had the potential to differentiate into OEC-like cells on the three-dimensional collagen scaffolds in vitro.

Blood pressure goal achievement with olmesartan medoxomil-based treatment: additional analysis of the OLMEBEST study.

Barrios Vivencio , Escobar Carlos , Calderon Alberto , Böhm Michael
Vasc Health Risk Manag.2009 ; 5():723-9.
PMID: 19756164[]

先週： 4位 14view,7users 保存 要約 閉じる

AIMS: Guidelines recommend blood pressure (BP) in hypertensive patients should be <140 systolic BP (SBP) and <90 diastolic BP (DBP) mmHg. This analysis assessed goal rate achievement in hypertensive patients receiving olmesartan-based treatment in the OLMEBEST study. METHODS: Patients with essential hypertension (DBP > or = 90 mmHg and <110 mmHg) received open-label olmesartan medoxomil 20 mg/day (n = 2306). After 8 weeks, patients with DBP > or = 90 mmHg (n = 627) were randomized to 4 weeks' double-blind treatment with olmesartan 40 mg/day monotherapy or olmesartan 20 mg/day plus hydrochlorothiazide (HCTZ) 12.5 mg/day. For this analysis, the numbers and proportions of patients who achieved SBP < 140 mmHg and/or DBP < 90 mmHg at the end of the 4 weeks were calculated. RESULTS: In patients who achieved DBP normalization (<90 mmHg) at week 8 (n = 1546) and continued open-label olmesartan 20 mg/day, 66.7% achieved SBP/DBP < 140/90 mmHg at Week 12. In patients who did not achieve DBP normalization at Week 8, 26.8% of those randomized to olmesartan 40 mg/day and 42.5% of those randomized to olmesartan 20 mg/day plus HCTZ 12.5 mg/day achieved a SBP/DBP < 140/90 mmHg at Week 12. CONCLUSION: Olmesartan 40 mg/day and olmesartan 20 mg/day plus HCTZ 12.5 mg/day allow substantial proportions of patients to achieve BP goals.

Mesenchymal stem cells increase hippocampal neurogenesis and counteract depressive-like behavior.

Mol Psychiatry.2009 Oct 27 ; ():.
PMID: 19859069[]

先週： 5位 20view,7users 保存 要約 閉じる

Adult bone marrow-derived mesenchymal stem cells (MSCs) are regarded as potential candidates for treatment of neurodegenerative disorders, because of their ability to promote neurogenesis. MSCs promote neurogenesis by differentiating into neural lineages as well as by expressing neurotrophic factors that enhance the survival and differentiation of neural progenitor cells. Depression has been associated with impaired neurogenesis in the hippocampus and dentate gyrus. Therefore, the aim of this study was to analyze the therapeutic potential of MSCs in the Flinders sensitive line (FSL), a rat animal model for depression. Rats received an intracerebroventricular injection of culture-expanded and 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI)-labeled bone marrow-derived MSCs (10(5) cells). MSC-transplanted FSL rats showed significant improvement in their behavioral performance, as measured by the forced swim test and the dominant-submissive relationship (DSR) paradigm. After transplantation, MSCs migrated mainly to the ipsilateral dentate gyrus, CA1 and CA3 regions of the hippocampus, and to a lesser extent to the thalamus, hypothalamus, cortex and contralateral hippocampus. Neurogenesis was increased in the ipsilateral dentate gyrus and hippocampus of engrafted rats (granular cell layer) and was correlated with MSC engraftment and behavioral performance. We therefore postulate that MSCs may serve as a novel modality for treating depressive disorders.Molecular Psychiatry advance online publication, 27 October 2009; doi:10.1038/mp.2009.110.

Adult satellite cells and embryonic muscle progenitors have distinct genetic requirements.

Lepper Christoph , Conway Simon J , Fan Chen-Ming
Nature.2009 Jul 30 ; 460(7255):627-31.
PMID: 19554048[]

先週： 6位 30view,6users 保存 要約 閉じる

Myogenic potential, survival and expansion of mammalian muscle progenitors depend on the myogenic determinants Pax3 and Pax7 embryonically, and Pax7 alone perinatally. Several in vitro studies support the critical role of Pax7 in these functions of adult muscle stem cells (satellite cells), but a formal demonstration has been lacking in vivo. Here we show, through the application of inducible Cre/loxP lineage tracing and conditional gene inactivation to the tibialis anterior muscle regeneration paradigm, that, unexpectedly, when Pax7 is inactivated in adult mice, mutant satellite cells are not compromised in muscle regeneration, they can proliferate and reoccupy the sublaminal satellite niche, and they are able to support further regenerative processes. Dual adult inactivation of Pax3 and Pax7 also results in normal muscle regeneration. Multiple time points of gene inactivation reveal that Pax7 is only required up to the juvenile period when progenitor cells make the transition into quiescence. Furthermore, we demonstrate a cell-intrinsic difference between neonatal progenitor and adult satellite cells in their Pax7-dependency. Our finding of an age-dependent change in the genetic requirement for muscle stem cells cautions against inferring adult stem-cell biology from embryonic studies, and has direct implications for the use of stem cells from hosts of different ages in transplantation-based therapy.

Angiotensin II receptor blocker and statins lower elevated levels of osteopontin in essential hypertension-Results from the EUTOPIA trial.

Atherosclerosis.2009 Sep 12 ; ():.
PMID: 19801149[]

先週： 7位 16view,5users 保存 要約 閉じる

BACKGROUND: Osteopontin is a pleiotropic cytokine that has been implicated as a key factor in the development of atherosclerosis, a major complication of hypertension. We have earlier shown that olmesartan reduces mediators of vascular inflammation in patients with hypertension and cardiovascular disease. We aimed at studying the effect of olmesartan and/or pravastatin on osteopontin plasma levels, and the association between vascular inflammation markers and osteopontin in hypertensive patients. METHODS: We assessed a panel of vascular inflammation markers and osteopontin during 12 weeks of therapy with 20mg olmesartan (n=94) or placebo (n=96) in a prospective, double-blind, multi-center study in patients with essential hypertension (re-evaluation of the EUTOPIA trial blood samples). Pravastatin (20mg) was added to the double-blind therapy at week 6 in both arms. The association of demographic variables and inflammation markers with osteopontin has been analyzed as well. RESULTS: Baseline osteopontin plasma concentrations in the study population were elevated compared to healthy controls (32.85+/-19.04ng/mL vs. 23.82+/-3.69ng/mL, p=0.027). Mono-therapy with olmesartan and co-therapy with pravastatin reduced levels of circulating osteopontin (p<0.001). The addition of pravastatin to the placebo treatment-arm resulted in a reduction of osteopontin levels as well (p<0.01). osteopontin plasma levels correlated with VCAM-1 (r=0.27; p=0.0002), ICAM-1 (r=0.18; p=0.015), IL-6 (r=0.35; p<0.0001) and hsCRP (r=0.22; p=0.0022). CONCLUSION: We show, for the first time, that olmesartan significantly decreases osteopontin concentrations. Co-therapy with pravastatin also reduces osteopontin levels. Elevated osteopontin levels in hypertensive patients correlate with adhesion molecules and inflammation markers.

VSOP/Hv1 proton channels sustain calcium entry, neutrophil migration, and superoxide production by limiting cell depolarization and acidification.

El Chemaly Antoun , Okochi Yoshifumi , Sasaki Mari , Arnaudeau Serge , Okamura Yasushi , Demaurex Nicolas
J Exp Med.2009 Dec 21 ; ():.
PMID: 20026664[]

先週： 83位 1view,5users 保存 要約 閉じる

Neutrophils kill microbes with reactive oxygen species generated by the NADPH oxidase, an enzyme which moves electrons across membranes. Voltage-gated proton channels (voltage-sensing domain only protein [VSOP]/Hv1) are required for high-level superoxide production by phagocytes, but the mechanism of this effect is not established. We show that neutrophils from VSOP/Hv1(-/-) mice lack proton currents but have normal electron currents, indicating that these cells have a fully functional oxidase that cannot conduct protons. VSOP/Hv1(-/-) neutrophils had a more acidic cytosol, were more depolarized, and produced less superoxide and hydrogen peroxide than neutrophils from wild-type mice. Hydrogen peroxide production was rescued by providing an artificial conductance with gramicidin. Loss of VSOP/Hv1 also aborted calcium responses to chemoattractants, increased neutrophil spreading, and decreased neutrophil migration. The migration defect was restored by the addition of a calcium ionophore. Our findings indicate that proton channels extrude the acid and compensate the charge generated by the oxidase, thereby sustaining calcium entry signals that control the adhesion and motility of neutrophils. Loss of proton channels thus aborts superoxide production and causes a severe signaling defect in neutrophils.

Localization of jointless-2 gene in the centromeric region of tomato chromosome 12 based on high resolution genetic and physical mapping.

Budiman M A , Chang S-B , Lee S , Yang T J , Zhang H-B , de Jong H , Wing R A
Theor Appl Genet.2004 Jan ; 108(2):190-6.
PMID: 14504748[]

先週： 8位 13view,5users 保存 要約 閉じる

Abscission is a universal process whereby plants shed their organs, such as flowers, fruit and leaves. In tomato, the non-allelic mutations jointless and jointless-2 have been discovered as recessive mutations that completely suppress the formation of pedicel abscission zones. A high resolution genetic map of jointless-2 was constructed using 1,122 jointless F2 plants. Restriction fragment length polymorphism (RFLP) marker RPD140 completely co-segregated with the jointless-2 locus and mapped in a 2.4 cM interval between RFLP markers CD22 and TG618. To chromosome walk to jointless-2, all three markers were used to screen a bacterial artificial chromosome (BAC) library and contigs were developed. Intensive efforts to expand and merge the BAC contigs were unsuccessful because of the highly repetitive sequence content on the distal ends of each contig. To determine the physical distance between and the orientation of the three contigs, we used high resolution pachytene fluorescence in situ hybridization (FISH) mapping. The RPD140 contig was positioned in the centromeric region of chromosome 12 between two large pericentric heterochromatin blocks, about 50 Mb from the TG618 contig on the short arm and 10 Mb from the CD22 contig on the long arm, respectively. Based on high resolution genetic and physical mapping, we conclude that the jointless-2 gene is located within or near the chromosome 12 centromere where 1 cM is approximately 25 Mb in length.

In-depth sequence analysis of the tomato chromosome 12 centromeric region: identification of a large CAA block and characterization of pericentromere retrotranposons.

Yang Tae-Jin , Lee Seunghee , Chang Song-Bin , Yu Yeisoo , de Jong Hans , Wing Rod A
Chromosoma.2005 Jul ; 114(2):103-17.
PMID: 15965704[]

先週： 9位 12view,5users 保存 要約 閉じる

We sequenced a continuous 326-kb DNA stretch of a microscopically defined centromeric region of tomato chromosome 12. A total of 84% of the sequence (270 kb) was composed of a nested complex of repeat sequences including 27 retrotransposons, two transposable elements, three MITEs, two terminal repeat retrotransposons in miniature (TRIMs), ten unclassified repeats and three chloroplast DNA insertions. The retrotransposons were grouped into three families of Ty3-Gypsy type long terminal repeat (LTR) retrotransposons (PCRT1-PCRT3) and one LINE-like retrotransposon (PCRT4). High-resolution fluorescence in situ hybridization analyses on pachytene complements revealed that PCRT1a occurs on the pericentromere heterochromatin blocks. PCRT1 was the prevalent retrotransposon family occupying more than 60% of the 326-kb sequence with 19 members grouped into eight subfamilies (PCRT1a-PCRT1h) based on LTR sequence. The PCRT1a subfamily is a rapidly amplified element occupying tens of megabases. The other PCRT1 subfamilies (PCRT1b-PCRT1h) were highly degenerated and interrupted by insertions of other elements. The PCRT1 family shows identity with a previously identified tomato-specific repeat TGR2 and a CENP-B like sequence. A second previously described genomic repeat, TGR3, was identified as a part of the LTR sequence of an Athila-like PCRT2 element of which four copies were found in the 326-kb stretch. A large block of trinucleotide microsatellite (CAA)n occupies the centromere and large portions of the flanking pericentromere heterochromatin blocks of chromosome 12 and most of the other chromosomes. Five putative genes in the remaining 14% of the centromere region were identified, of which one is similar to a transcription regulator (ToCPL1) and a candidate jointless-2 gene.

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週間人気ジャーナルランキング - 閲覧数 (2010/03/13/ 09時更新)

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The Journal of biological chemistry

先週： 1位 5,273view , 123users

Proceedings of the National Academy of Sciences of the United States of America

先週： 2位 2,578view , 85users

Journal of immunology (Baltimore, Md. : 1950)

先週： 3位 2,252view , 59users

Blood

先週： 5位 1,865view , 28users

Biochemistry

先週： 4位 1,762view , 11users

Journal of virology

先週： 8位 1,649view , 16users

Cancer research

先週： 6位 1,470view , 35users

Science (New York, N.Y.)

先週： 10位 1,414view , 39users

Biochemical and biophysical research communications

先週： 9位 1,395view , 42users

Giornale di psichiatria e di neuropatologia

先週： 7位 1,316view , 38users

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週間人気ジャーナルランキング - 保存数 (2010/03/13/ 09時更新)

閲覧数ランキング

The Journal of biological chemistry

先週： 1位 5,273view , 123users

Proceedings of the National Academy of Sciences of the United States of America

先週： 2位 2,578view , 85users

PloS one

先週： 4位 830view , 60users

Journal of immunology (Baltimore, Md. : 1950)

先週： 3位 2,252view , 59users

Hypertension research : official journal of the Japanese Society of Hypertension

先週： 6位 238view , 47users

Journal of agricultural and food chemistry

先週： 5位 647view , 47users

European journal of immunology

先週： 8位 503view , 43users

Biochemical and biophysical research communications

先週： 7位 1,395view , 42users

Science (New York, N.Y.)

先週： 9位 1,414view , 39users

Giornale di psichiatria e di neuropatologia

先週： 10位 1,316view , 38users

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RORgamma-expressing Th17 cells induce murine chronic intestinal inflammation via redundant effects of IL-17A and IL-17F.

Leppkes Moritz , Becker Christoph , Ivanov Ivaylo I , Hirth Sebastian , Wirtz Stefan , Neufert Clemens , Pouly Sandrine , Murphy Andrew J , Valenzuela David M , Yancopoulos George D , Becher Burkhard , Littman Dan R , Neurath Markus F
Gastroenterology.2009 Jan ; 136(1):257-67.
PMID: 18992745[]

2009/01/23 保存 要約 閉じる

BACKGROUND AND AIMS: IL-17-producing CD4(+) T-helper cells (Th17) contribute to chronic autoimmune inflammation in the brain, and levels of Th17-derived cytokines increase in patients with colitis, suggesting a role in pathogenesis. We analyzed the roles of Th17 cells and the transcription factor retinoic acid receptor-related organ receptor (ROR)gamma, which regulates Th17 differentiation, in chronic intestinal inflammation. METHODS: Using an adoptive transfer model of colitis, we compared the colitogenic potential of wild-type, interleukin-17A (IL-17A)-, IL-17F-, IL-22-, and RORgamma-deficient CD4(+)CD25(-) T cells in RAG1-null mice. RESULTS: Adoptive transfer of IL-17A-, IL-17F-, or IL-22-deficient T lymphocytes into RAG1-null mice caused severe colitis that was indistinguishable from that caused by wild-type cells. In contrast, transfer of RORgamma-null T cells failed to increase mucosal IL-17 cytokine levels and did not induce colitis. Treatment with IL-17A was able to restore colitis after transfer of RORgamma-null T cells, indicating a crucial role for Th17 cells in pathogenesis. Treatment of RAG1 mice that received IL-17F-null (but not wild-type) T cells with a neutralizing anti-IL-17A antibody significantly suppressed disease, indicating redundant biological effects of IL-17A and IL-17F. CONCLUSIONS: We have identified a crucial role of RORgamma-expressing Th17 cells in chronic intestinal inflammation. RORgamma controls IL-17A and IL-17F production, and these cytokines have a redundant but highly pathogenic role in gut inflammation. Reagents that target RORgamma or a combination of anti-IL-17A and anti-IL-17F might be developed as therapeutics for chronic colitis.

2',5,7-Trihydroxy-4',5'-(2,2-dimethylchromeno)-8-(3-hydroxy-3-methylbutyl) flavanone purified from Cudrania tricuspidata induces apoptotic cell death of human leukemia U937 cells.

Rho Yoon-Hwa , Yoon Soo-Hyun , Kim Eun-Kyung , Kang Ji-Young , Lee Byong-Won , Park Ki-Hun , Bae Young-Seuk
Nat Prod Res.2007 Jun ; 21(7):616-24.
PMID: 17613819[]

2007/07/06 保存 要約 閉じる

Cellular DNA topoisomerase I is an important target in cancer chemotherapy. A chloroform extract of the root barks of Cudrania tricuspidata showed an inhibitory effect on mammalian DNA topoisomerase I. The topoisomerase I inhibitory compound was purified and identified as 2',5,7-trihydroxy-4',5'-(2,2-dimethylchromeno)-8-(3-hydroxy-3-methylbutyl) flavanone. The compound, temporarily designated as PKH-3, was shown to inhibit the activity of topoisomerase I with IC50 about 1.0 mM. Concentration of 10 microM PKH-3 caused 50% growth inhibition of human cancer cell U937. PKH-3-induced cell death was characterized with the cleavage of poly(ADP-ribose) polymerase (PARP) and pro-caspase 3. Furthermore, PKH-3 induced the fragmentation of DNA into multiples of 180 b.p. (an apoptotic DNA ladder), indicating that the inhibitor triggered apoptosis. This induction of apoptosis by PKH-3 was also confirmed using flow cytometry analysis. Taken together, these results suggest that PKH-3 may function by inhibiting oncogenic disease, at least in part, through the inhibition of topoisomerase I activity.

The type Ia supernova SNLS-03D3bb from a super-Chandrasekhar-mass white dwarf star.

Howell D Andrew , Sullivan Mark , Nugent Peter E , Ellis Richard S , Conley Alexander J , Le Borgne Damien , Carlberg Raymond G , Guy Julien , Balam David , Basa Stephane , Fouchez Dominique , Hook Isobel M , Hsiao Eric Y , Neill James D , Pain Reynald , Perrett Kathryn M , Pritchet Christopher J
Nature.2006 Sep 21 ; 443(7109):308-11.
PMID: 16988705[]

2006/09/21 保存 要約 閉じる

The accelerating expansion of the Universe, and the need for dark energy, were inferred from observations of type Ia supernovae. There is a consensus that type Ia supernovae are thermonuclear explosions that destroy carbon-oxygen white dwarf stars that have accreted matter from a companion star, although the nature of this companion remains uncertain. These supernovae are thought to be reliable distance indicators because they have a standard amount of fuel and a uniform trigger: they are predicted to explode when the mass of the white dwarf nears the Chandrasekhar mass of 1.4 solar masses (M(o)). Here we show that the high-redshift supernova SNLS-03D3bb has an exceptionally high luminosity and low kinetic energy that both imply a super-Chandrasekhar-mass progenitor. Super-Chandrasekhar-mass supernovae should occur preferentially in a young stellar population, so this may provide an explanation for the observed trend that overluminous type Ia supernovae occur only in 'young' environments. As this supernova does not obey the relations that allow type Ia supernovae to be calibrated as standard candles, and as no counterparts have been found at low redshift, future cosmology studies will have to consider possible contamination from such events.

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週間オススメ論文ランキング - 保存数 (2010/03/15/ 22時更新)

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The type Ia supernova SNLS-03D3bb from a super-Chandrasekhar-mass white dwarf star.

Howell D Andrew , Sullivan Mark , Nugent Peter E , Ellis Richard S , Conley Alexander J , Le Borgne Damien , Carlberg Raymond G , Guy Julien , Balam David , Basa Stephane , Fouchez Dominique , Hook Isobel M , Hsiao Eric Y , Neill James D , Pain Reynald , Perrett Kathryn M , Pritchet Christopher J
Nature.2006 Sep 21 ; 443(7109):308-11.
PMID: 16988705[]

307view,1users 保存 要約 閉じる

The accelerating expansion of the Universe, and the need for dark energy, were inferred from observations of type Ia supernovae. There is a consensus that type Ia supernovae are thermonuclear explosions that destroy carbon-oxygen white dwarf stars that have accreted matter from a companion star, although the nature of this companion remains uncertain. These supernovae are thought to be reliable distance indicators because they have a standard amount of fuel and a uniform trigger: they are predicted to explode when the mass of the white dwarf nears the Chandrasekhar mass of 1.4 solar masses (M(o)). Here we show that the high-redshift supernova SNLS-03D3bb has an exceptionally high luminosity and low kinetic energy that both imply a super-Chandrasekhar-mass progenitor. Super-Chandrasekhar-mass supernovae should occur preferentially in a young stellar population, so this may provide an explanation for the observed trend that overluminous type Ia supernovae occur only in 'young' environments. As this supernova does not obey the relations that allow type Ia supernovae to be calibrated as standard candles, and as no counterparts have been found at low redshift, future cosmology studies will have to consider possible contamination from such events.

2',5,7-Trihydroxy-4',5'-(2,2-dimethylchromeno)-8-(3-hydroxy-3-methylbutyl) flavanone purified from Cudrania tricuspidata induces apoptotic cell death of human leukemia U937 cells.

Rho Yoon-Hwa , Yoon Soo-Hyun , Kim Eun-Kyung , Kang Ji-Young , Lee Byong-Won , Park Ki-Hun , Bae Young-Seuk
Nat Prod Res.2007 Jun ; 21(7):616-24.
PMID: 17613819[]

270view,1users 保存 要約 閉じる

Cellular DNA topoisomerase I is an important target in cancer chemotherapy. A chloroform extract of the root barks of Cudrania tricuspidata showed an inhibitory effect on mammalian DNA topoisomerase I. The topoisomerase I inhibitory compound was purified and identified as 2',5,7-trihydroxy-4',5'-(2,2-dimethylchromeno)-8-(3-hydroxy-3-methylbutyl) flavanone. The compound, temporarily designated as PKH-3, was shown to inhibit the activity of topoisomerase I with IC50 about 1.0 mM. Concentration of 10 microM PKH-3 caused 50% growth inhibition of human cancer cell U937. PKH-3-induced cell death was characterized with the cleavage of poly(ADP-ribose) polymerase (PARP) and pro-caspase 3. Furthermore, PKH-3 induced the fragmentation of DNA into multiples of 180 b.p. (an apoptotic DNA ladder), indicating that the inhibitor triggered apoptosis. This induction of apoptosis by PKH-3 was also confirmed using flow cytometry analysis. Taken together, these results suggest that PKH-3 may function by inhibiting oncogenic disease, at least in part, through the inhibition of topoisomerase I activity.

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Total place--part 2. Why working together boosts independence.

Mooney Helen
Health Serv J.2010 Feb 11 ; 120(6193):22-3.
PMID: 20225390[]

2010/03/12 保存 要約はありません

Publuc health. Birmingham gets fit with a purpose.

Shepherd Stuart
Health Serv J.2010 Feb 11 ; 120(6193):20-1.
PMID: 20225389[]

2010/03/12 保存 要約はありません

Separate ways to offer dignity.

Stevens Janice
Health Serv J.2010 Feb 11 ; 120(6193):14-5.
PMID: 20225388[]

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Lansley points to joint powers in public health.

Evans Rebecca
Health Serv J.2010 Feb 11 ; 120(6193):12-3.
PMID: 20225387[]

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Quality strongly linked to increases in managers.

Santry Charlotte
Health Serv J.2010 Feb 11 ; 120(6193):4-5.
PMID: 20225386[]

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Following a rural recipe. South Dakota's H1N1 strategy might provide pandemic blueprint.

Zigmond Jessica
Mod Healthc.2010 Feb 22 ; 40(8):32-3.
PMID: 20225385[]

2010/03/12 保存 要約はありません

Trustees of the year 2010. To learn how to battle costs, Hawk got involved at Memorial Hospital.

Wilson Linda
Mod Healthc.2010 Feb 22 ; 40(8):28, 30.
PMID: 20225384[]

2010/03/12 保存 要約はありません

Trustees of the year 2010. Walker helped guide Baptist Hospitals through expansion, affiliations.

Wilson Linda
Mod Healthc.2010 Feb 22 ; 40(8):28, 30.
PMID: 20225383[]

2010/03/12 保存 要約はありません

Trustees of the year 2010. Turning it around.

Wilson Linda
Mod Healthc.2010 Feb 22 ; 40(8):26, 30.
PMID: 20225382[]

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Clogged up. Efforts to train more minority doctors remain stalled as population diversifies.

Merchant Juanita , Omary Bishr
Mod Healthc.2010 Feb 22 ; 40(8):24.
PMID: 20225381[]

2010/03/12 保存 要約はありません

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