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よく検索されるキーワード

Olmesartan
pravastatin
azelnidipine
valsartan
candesartan
carvedilol
telmisartan
Alzheimer
prasugrel
irbesartan

よく検索されるジャーナル

Journal of agricultural and food chemistry
cell
Nature
Blood
Science
The Journal of biological chemistry
Blood
Biochemical and biophysical research communications
Biochem Biophys Res Commun
Angew Chem Int Ed Engl

よく検索される著者

Wang Y
Zhang S
Lee SJ
Kanie O
Wang C
Nakao K
Zhang Y
Zhao L
Cheng CY
Asanuma T

Type I collagen inhibits differentiation and promotes a stem cell-like phenotype in human colorectal carcinoma cells.

Kirkland SC

Br J Cancer.2009 Jul 21 ; 101(2):320-6.

PubMedで表示

Department of Histopathology, Imperial College London, DuCane Road, London W12 ONN, UK. s.kirkland@imperial.ac.uk

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BACKGROUND: Human colorectal cancer is caused by mutations and is thought to be maintained by a population of cancer stem cells. Further phenotypic changes occurring at the invasive edge suggest that colon cancer cells are also regulated by their microenvironment. Type I collagen, a promoter of the malignant phenotype in pancreatic carcinoma cells, is highly expressed at the invasive front of human colorectal cancer. METHODS: This study investigates the role of type I collagen in specifying the colorectal cancer cell phenotype. The effect of type I collagen on morphology, localisation of cell-cell adhesion proteins, differentiation and stem cell-like characteristics was examined in a panel of human colorectal carcinoma cell lines. RESULTS: Human colorectal carcinoma cells grown on type I collagen in serum-free medium show an epithelial-mesenchymal-like transition (EMT-like), assuming a more flattened less cohesive morphology. Type I collagen downregulates E-cadherin and beta-catenin at cell-cell junctions. Furthermore, type I collagen inhibits differentiation, increases clonogenicity and promotes expression of stem cell markers CD133 and Bmi1. Type I collagen effects were partially abrogated by a function-blocking antibody to alpha2 integrin. CONCLUSION: Together, these results indicate that type I collagen promotes expression of a stem cell-like phenotype in human colorectal cancer cells likely through alpha2beta1 integrin.
PMID: 19568234 [PubMed - indexed for MEDLINE]

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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： 3位

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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

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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.

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： 1位

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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.

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： 5位

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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： 6位

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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： 4位

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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.

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

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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.

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

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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.

Trypanocidal diarylheptanoids from Aframomum letestuianum.

Kamnaing Pierre , Tsopmo Apollinaire , Tanifum Eric A , Tchuendem Marguerite H K , Tane Pierre , Ayafor Johnson F , Sterner Olov , Rattendi Donna , Iwu Maurice M , Schuster Brian , Bacchi Cyrus
J Nat Prod.2003 Mar ; 66(3):364-7.
PMID: 12662093[]

先週： 9位

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Three new diarylheptanoids, (4Z,6E)-5-hydroxy-1-(4-hydroxy-3-methoxyphenyl)-7-(4-hydroxyphenyl)hepta-4,6-dien-3-one, letestuianin A (1), (4Z,6E)-5-hydroxy-1,7-bis(4-hydroxy-3-methoxyphenyl)hepta-4,6-dien-3-one, letestuianin B (2), and 1,7-bis(4-hydroxyphenyl)heptan-3,5-dione, letestuianin C (3), as well as the known (4Z,6E)-5-hydroxy-1,7-bis(4-hydroxyphenyl)hepta-4,6-dien-3-one (5) were isolated from Aframomum letestuianum. The known flavonoids 3-acetoxy-5,7,4'-trihydroxyflavanone, 3-acetoxy-7-methoxy-5,4'-dihydroxyflavanone, 7-methoxy-3,5,4'-trihydroxyflavone, and 3,3',4',5,7-pentahydroxyflavan were also obtained from this plant. Their structures were determined using a combination of 1D and 2D NMR techniques. The four diarylheptanoids were tested for growth inhibitory activity in vitro versus bloodstream forms of African trypanosomes. IC(50) values in the range of 1-3 microg/mL were found for compounds 3 and 5.

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： 18位

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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.

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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

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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

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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

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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

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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

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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

57view,6users

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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

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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.

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

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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

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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.

Sodium-translocating NADH:Quinone oxidoreductase as a redox-driven ion pump.

Verkhovsky Michael I , Bogachev Alexander V
Biochim Biophys Acta.2010 Jan 4 ; ():.
PMID: 20056102[]

先週： 10位

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The Na(+)-translocating NADH:ubiquinone oxidoreductase (Na(+)-NQR) is a component of the respiratory chain of various bacteria. This enzyme is an analogous but not homologous counterpart of mitochondrial Complex I. Na(+)-NQR drives the same chemistry and also uses released energy to translocate ions across the membrane, but it pumps Na(+) instead of H(+). Most likely the mechanism of sodium pumping is quite different from that of proton pumping (for example, it could not accommodate the Grotthuss mechanism of ion movement); this is why the enzyme structure, subunits and prosthetic groups are completely special. This review summarizes modern knowledge on the structural and catalytic properties of bacterial Na(+)-translocating NADH:quinone oxidoreductases. The sequence of electron transfer through the enzyme cofactors and thermodynamic properties of those cofactors are discussed. The resolution of the intermediates of the catalytic cycle and localization of sodium-dependent steps are combined in a possible molecular mechanism of sodium transfer by the enzyme.

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The Journal of biological chemistry

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Biochemical and biophysical research communications

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Science (New York, N.Y.)

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The Journal of biological chemistry

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4,703view , 113users

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

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2,532view , 81users

Journal of immunology (Baltimore, Md. : 1950)

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Hypertension research : official journal of the Japanese Society of Hypertension

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Biochemical and biophysical research communications

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European journal of immunology

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Science (New York, N.Y.)

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Giornale di psichiatria e di neuropatologia

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Optimization of magnetosonoporation for stem cell labeling.

Xie Daohai , Qiu Bensheng , Walczak Piotr , Li Xubin , Ruiz-Cabello Jesus , Minoshima Satoshi , Bulte Jeff W M , Yang Xiaoming
NMR Biomed.2010 Mar 8 ; ():.
PMID: 20213856[]

2010/03/09

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Recent advances in magnetic cell labeling have taken place with the development of a magnetosonoporation (MSP) technique. The aim of this study was to optimize the MSP protocol in order to achieve high cell viability and intracellular uptake of MR contrast agents. First, we determined the sub-optimal MSP parameters by evaluating the viabilities of C17.2 neural stem cells without Feridex using various MSP intensities ranging from 0.1 to 1 w/cm(2), duty cycles at 20%, 50% or 100%, and exposure times from 1-15 min. The sub-optimized MSP parameters with cell viabilities greater than 90% were further optimized by evaluating both cell viability and intracellular iron uptake when Feridex was used. We then used the optimized MSP parameters to determinate the optimal concentration of Feridex for magnetic cell labeling. Subsequently, we validated the feasibility of using MRI to track the migration of neural stem cells from the transplanted sites to glioma masses in four mouse brains when the cells had been labeled with Feridex using the optimized MSP protocol. The MRI findings were confirmed by histological correlations. In vitro experiments demonstrated that the optimal MSP protocol was achieved at 20% duty cycle, 0.3 w/cm(2) ultrasound intensity, 5-min exposure time and 1mg/mL Feridex. This study demonstrated that the optimized MSP cell labeling technique can achieve both high cell viability and intracellular uptake of MR contrast agents, and has the potential to be a useful cell labeling technique to facilitate future clinical translation of MRI-integrated cell therapy. Copyright (c) 2010 John Wiley & Sons, Ltd.

Correlates of chemosensory malingering.

Doty Richard L , Crastnopol Benjamin
Laryngoscope.2010 Mar 8 ; ():.
PMID: 20213794[]

2010/03/09

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OBJECTIVES/HYPOTHESIS:: Smell and taste tests are commonly employed to quantify chemosensory sequelae of head trauma, toxic exposures, and iatrogenesis. Malingering on forced-choice chemosensory tests can be detected by improbable responding. This study determined whether chemosensory test malingerers differ from nonmalingerers in terms of age, sex, education, and a range of self-reported behaviors and symptoms, potentially providing information of value for malingering detection. STUDY DESIGN:: Case control. METHODS:: Twenty-two chemosensory malingerers were identified from a large clinical database and matched, randomly, to 66 nonmalingerers on the basis of etiology. Differences in demographics and responses to intake questionnaire items were statistically assessed. Logistic regression was used to identify variables that best predicted malingering behavior. RESULTS:: Relative to nonmalingerers, malingerers reported significantly fewer allergies, dental problems, cigarettes smoked, surgical operations, nasal sinus problems, and use of medications, and significantly more putative symptom-related psychological duress, interference with daily activities, weight loss, decreased appetite, and taste loss. Litigation involvement was higher in malingerers than nonmalingerers. Age, sex, education, and length of symptom descriptions did not differentiate malingerers from nonmalingerers. CONCLUSIONS:: Malingerers of chemosensory tests exaggerate symptom severity and underreport factors that might be construed as contributing to their dysfunction, such as smoking behavior, medication use, and general health. This contrasts with the behavior of malingerers of psychiatric symptoms, who typically exaggerate their general health problems. These data suggest that careful review of past medical records should be used to verify patient reports to better detect chemosensory malingering in cases where financial or other external incentives are present. Laryngoscope, 2010.

A Hierarchical Model to Estimate Fish Abundance in Alpine Streams by using Removal Sampling Data from Multiple Locations.

Laplanche Christophe
Biom J.2010 Mar 8 ; ():.
PMID: 20213740[]

2010/03/09

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The author compares 12 hierarchical models in the aim of estimating the abundance of fish in alpine streams by using removal sampling data collected at multiple locations. The most expanded model accounts for (i) variability of the abundance among locations, (ii) variability of the catchability among locations, and (iii) residual variability of the catchability among fish. Eleven model reductions are considered depending which variability is included in the model. The more restrictive model considers none of the aforementioned variabilities. Computations of the latter model can be achieved by using the algorithm presented by Carle and Strub (Biometrics 1978, 34, 621-630). Maximum a posteriori and interval estimates of the parameters as well as the Akaike and the Bayesian information criterions of model fit are computed by using samples simulated by a Markov chain Monte Carlo method. The models are compared by using a trout (Salmo trutta fario) parr (0+) removal sampling data set collected at three locations in the Pyrénées mountain range (Haute-Garonne, France) in July 2006. Results suggest that, in this case study, variability of the catchability is not significant, either among fish or locations. Variability of the abundance among locations is significant. 95% interval estimates of the abundances at the three locations are [0.15, 0.24], [0.26, 0.36], and [0.45, 0.58] parrs per m(2). Such differences are likely the consequence of habitat variability.

Wound healing and protease inhibition activity of Bacoside-A, isolated from Bacopa monnieri wettest.

Sharath R , Harish B G , Krishna V , Sathyanarayana B N , Swamy H M Kumara
Phytother Res.2010 Mar 8 ; ():.
PMID: 20213670[]

2010/03/09

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Bacopa monnieri (L.) Wettest. (Scrophulariaceae) is a well-known medicinal herb. In the Indian system of medicine it is known as Brahmi (Sanskrit) and Indian water hyssop. Methanolic extract of Bacopa monnieri and its isolated constituent Bacoside-A were screened for wound healing activity. Bacoside-A was screened for wound healing activity by excision, incision and dead space wound on Swiss albino rats. Significant wound healing activity was observed in both extract and the Bacoside-A treated groups. The SDS-PAGE caseinolytic zymogram analysis of inhibition of matrix metalloproteases (MMPs) enzyme from the excision wound by Bacoside-A, an isolated constituent, was done with the concentrations 100 and 200 mumg/ml. In Bacoside-A treated groups, epithelialization of the excision wound was faster with a high rate (18.30 +/- 0.01 days) of wound contraction. The tensile strength of the incision wound was increased (538.47 +/- 0.14 g) in the Bacoside-A treated group. In the dead space wound model, the weight of the granuloma was also increased (89.15 +/- 0.08 g). The histological examination of the granuloma tissue of the Bacoside-A treated group showed increased cross-linking of collagen fibers and absence of monocytes. The wound healing activity of Bacoside-A was more effective in various wound models compared to the standard skin ointment Nitrofurazone. Copyright (c) 2010 John Wiley & Sons, Ltd.

Muscle Strength of the Cervical and Lumbar Spine in Triathletes.

Miltner O , Siebert C H , Müller-Rath R , Kieffer O
Z Orthop Unfall.2010 Mar 8 ; ():.
PMID: 20213602[]

2010/03/09

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AIM: The goal of this study was to analyse the muscle strength of the cervical and lumbar spine in ironman triathletes. The values were compared to the results obtained from a reference group. The test of the triathletes was carried out in an attempt to define a specific strength profile for these athletes. METHOD: In this study, 20 long-distance triathletes (slashed circle 37.3 +/- 7.6 years of age, slashed circle 1.80 +/- 0.1 m, slashed circle 73.7 +/- 6.0 kg) were evaluated with regard to their individual and sport-specific strengths of the cervical spine in 2 planes and of the trunk strengths in all 3 planes of motion. The trunk strength profile of the triathletes revealed good average results in the trunk extensors and the lateral flexors of the left trunk. The reference group is the data base of the company Proxomed(R), Alzenau. It is based on results of 1045 untrained, symptom-free subjects of different ages. RESULTS: Lumbar extension: The extension of the force values shows no significant difference from the reference group. Lumbar flexion: The flexion tests show highly significantly lower force values (5.025 +/- 0.81 N/kg vs. 6.67 +/- 0.6 N/kg) than the reference group. Flexion/extension: In the sagittal plane values for the triathletes demonstrate an imbalance in muscle strength ratios. The abdominal muscles turn in relation to the back extensor muscles too weakly to be very significant. Lumbar rotation: The force values of the athletes in both directions (right: 6.185 +/- 1.46 N/kg, left: 7.1 +/- 1.57 N/kg vs. 10.05 +/- 0.34 N/kg) are highly significantly (p </= 0.001) lower than the reference values. Ratio of rotation left/right: The ratio of left/right rotation in the reference group is set at 1 and thus shows an equally strong force level between the two sides. Lumbar lateral flexion: The triathletes do not show any significant differences between the force values. Compared to the reference group there is no significant difference to the left side flexion. In the lateral bending the athletes have significantly better values than the reference group. Ratio of lateral left/right: In the reference group the ratio is set at 1. For triathletes, it shows an average value of 0.93. This difference is not significant. Cervical extension: The extension of the force values (1.96 +/- 0.59 N/kg vs. 3.03 +/- 0.24 N/kg) shows a highly significant difference from the reference group. Cervical flexion: In flexion (1.3 +/- 0.42 N/kg vs. 2.17 +/- 0.22 N/kg) triathletes have highly significantly lower strength values than the reference group. Flexion/extension: The triathletes did not differ significantly from the reference values (0.69 +/- 0.23 and 0.72 +/- 0.08). Lateral cervical spine: In comparison to the reference group (left: 1.67 +/- 0.48 N/kg, right: 1.55 +/- 0.46 N/kg vs. 2.36 +/- 0.15 N/kg) in which there is left/right lateral flexion, there is a highly significant difference. Right lateral flexion is weaker than the left. Ratio of lateral left/right: The triathletes have a significant imbalance in the lateral flexion of the cervical spine compared to the reference group (1.07 +/- 0.15 to 1). CONCLUSION: In conclusion, in the triathlon there is a specific stress that is obviously not an adequate stimulus for the muscles of the cervical spine in order to achieve a balanced musculature and the athletes should be advised to practice a preventive approach with regard to these areas.

Exendin-4 Protects Pancreatic Beta Cells from the Cytotoxic Effect of Rapamycin by Inhibiting JNK and p38 Phosphorylation.

Kawasaki Y , Harashima S , Sasaki M , Mukai E , Nakamura Y , Harada N , Toyoda K , Hamasaki A , Yamane S , Yamada C , Yamada Y , Seino Y , Inagaki N
Horm Metab Res.2010 Mar 8 ; ():.
PMID: 20213584[]

2010/03/09

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It has been reported that the immunosuppressant rapamycin decreases the viability of pancreatic beta cells. In contrast, exendin-4, an analogue of glucagon-like peptide-1, has been found to inhibit beta cell death and to increase beta cell mass. We investigated the effects of exendin-4 on the cytotoxic effect of rapamycin in beta cells. Incubation with 10 nM rapamycin induced cell death in 12 h in murine beta cell line MIN6 cells and Wistar rat islets, but not when coincubated with 10 nM exendin-4. Rapamycin was found to increase phosphorylation of c-Jun amino-terminal kinase (JNK) and p38 in 30 minutes in MIN6 cells and Wistar rat islets while exendin-4 decreased their phosphorylation. Akt and extracellular signal-regulated kinase (ERK) were not involved in the cytoprotective effect of exendin-4. These results indicate that exendin-4 may exert its protective effect against rapamycin-induced cell death in pancreatic beta cells by inhibiting JNK and p38 signaling.

Computational identification and microarray-based validation of microRNAs in Oryctolagus cuniculus.

Liu Guiming , Fang Yongjun , Zhang Hongming , Li Yan , Li Xingang , Yu Jun , Wang Xumin
Mol Biol Rep.2010 Mar 7 ; ():.
PMID: 20213505[]

2010/03/09

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MicroRNAs (miRNAs) belong to a class of small non-coding RNAs that play important roles in complex biological processes through degradation of target mRNAs or repression of their translation. We exploited cross-species comparison to predict miRNAs and identified 266 genes encoding 274 mature miRNAs in Oryctolagus cuniculus. Comparative analyses among mammalian genomes demonstrated that most of the identified miRNAs and their clusters are ancient in origin and conserved among mammals but a few clades as well as some species-specific miRNAs exhibit an ongoing evolutionary process where gain and loss of individual miRNAs have occurred through tandem duplications and random mutations. Our microarray- and RT-PCR-based analyses and target prediction reveal specific expression patterns in brain, spleen, muscle, heart, and ovary, and significant over-representations in certain GO categories as regarded to their mRNA targets include genes that play key roles in signal transduction and transcriptional regulation.

The preperitoneal loop in inguinal hernia repair following the totally extraperitoneal technique.

Mainik F , Quast G , Flade-Kuthe R , Kuthe A , Schroedl F
Hernia.2010 Mar 6 ; ():.
PMID: 20213455[]

2010/03/09

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BACKGROUND: With increasing experience in totally extraperitoneal (TEP) hernia repair, we observed an anatomical structure not described in the literature. It is a loop-like structure under the ductus deferens or ligamentum teres uteri anchored laterally and medially to the peritoneum. Relatively constant in distance to the inner inguinal ring and individual in the grade of prominence, it inhibits correct patch placement medially. To identify and describe this so-called preperitoneal loop (pl), we performed this study. METHODS: Between February 2nd and July 15th 2006, all patients undergoing a TEP procedure at our institution in primary inguinal hernia without previous operations in the lower abdomen were included. The main topic was the prominence and distance to the inner inguinal ring of the pl and histological examinations were made. RESULTS: A total of 219 patients (194 male, 25 female) were included, with 97 right-side, 64 left-side and 58 bilateral hernias. The pl could be shown in 206 cases (94%), the distance to the inner ring was up to 1.5 cm in 60, between 1.5 and 3.0 cm in 112, and over 3 cm in 34 cases. Anatomical examinations showed smaller blood vessels embedded in fatty tissue and surrounded by collagen fibres (standard haematoxylin eosin [HE]) and collagen connective tissue strongly filled with elastic fibres and, occasionally, nerve fibres and lymphatic capillaries (van Gieson). CONCLUSIONS: The pl is a very constant structure that is independent of gender and hernia type and size. In most cases, it is found close to the inner inguinal ring and, therefore, has to be cut for adequate parietalisation of cord structures/ligamentum teres uteri and correct mesh placement medially. As no mesothel was found, the origin of pl might be the deeper sheet of transversalis fascia.

Mesenchymal-to-epithelial transition determinants as characteristics of ovarian carcinoma effusions.

Elloul Sivan , Vaksman Olga , Stavnes Helene Tuft , Trope Claes G , Davidson Ben , Reich Reuven
Clin Exp Metastasis.2010 Mar 7 ; ():.
PMID: 20213325[]

2010/03/09

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The present study investigated the intracellular regulation of E-cadherin in ovarian carcinoma. E-cadherin expression and regulation by Snail and Pak1 were studied in ES-2 and OVCAR-3 ovarian cancer cells in vitro. Twist1, Zeb1 and Vimentin mRNA expression and HIF-1alpha protein expression were analyzed in 80 and 189 clinical specimens, respectively. OVCAR-3 cells incubated with an anti-E-cadherin antibody formed smaller and looser spheroids compared to controls. Snail silencing using Small Hairpin RNA in ES-2 cells reduced invasion and MMP-2 activity, with unaltered cellular morphology. Using dominant negative (DN) and constitutively active (CA) Pak1 constructs, we found that DN Pak1 ES-2 and OVCAR-3 clones had reduced attachment to matrix proteins, invasion and MMP-2 activity compared to CA and wild-type cells. DN Pak1 ES-2 cells also bound less to LP9 mesothelial cells. DN Pak1 OVCAR-3 cells had lower Vimentin levels. Snail expression was lower in cultured effusions compared to primary carcinomas, and was cytoplasmic rather than nuclear. Twist1 (P < 0.001), Zeb1 (P = 0.003) and Vimentin (P = 0.03) mRNA expression was significantly higher in solid metastases compared to primary carcinomas and effusions. HIF-1alpha protein expression was lower in effusions compared to primary carcinomas and solid metastases (P = 0.033). Our data suggest that the previously reported E-cadherin re-expression in ovarian carcinoma effusions is regulated by Pak1. The transient nature of E-cadherin expression during ovarian carcinoma progression is probably the result of partial epithelial-to-mesenchymal transition (EMT) and the reverse process of mesenchymal-to-epithelial-like transition (MET). Expression of the EMT-related molecules Twist, Zeb1, Vimentin and HIF-1alpha is anatomic site-dependent in ovarian carcinoma.

Vertebroplasty with self-locking hexagonal metal implants shows comparable primary and secondary stiffness to PMMA cement augmentation techniques in a biomechanical vertebral compression fracture model.

Schmoelz W , Disch A C , Huber J F
Eur Spine J.2010 Mar 7 ; ():.
PMID: 20213299[]

2010/03/09

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With the growing incidence of vertebral compression fractures in elderly patients having a fair overall health condition, minimal-invasive treatment techniques are getting in focus of surgical therapy. Cement augmentation is widely performed and its complications and mechanical limitations are well described. Implants avoiding the side effects of cement augmentation while reaching the same level of stability would be desirable. The primary and secondary stability of a new augmentation method with self-locking hexagonal metal implants were investigated and compared with the performance of established augmentation options. 18 fresh-frozen human spinal specimens (Th12-L2/L3-L5) were tested with pure moments of 7.5 Nm in a six-degree-of-freedom spine simulator to investigate primary and secondary stability of three augmentation techniques: (1) vertebroplasty, (2) PMMA filled cavity and (3) hexagonal metal implants. An increasing three-step cyclic loading model was included. Elastic displacement and height loss under loading did not show significant differences between the three test groups. Investigation of primary and secondary stability evenly demonstrated comparable results for all techniques indicating an insufficiency to stabilise the fracture with higher load cycles. The newly introduced method for augmentation with the metal implant Spine Pearls achieved comparable results to bone cement based techniques in a biomechanical in vitro study. Midterm and longterm reduction preservation and ingrowth of the implants have to be proven in further studies.

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