Azumamides A-E: histone deacetylase inhibitory cyclic tetrapeptides from the marine sponge Mycale izuensis.
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Angiogenesis Inhibitors↗
Biomedical subjects
Satoru Yoshida
Publications and source records attributed to Satoru Yoshida.
Isolation of multipotent neural crest-derived stem cells from the adult mouse cornea.
We report the presence of neural crest-derived corneal precursors (COPs) that initiate spheres by clonal expansion from a single cell. COPs expressed the stem cell markers nestin, Notch1, Musashi-1, and ABCG2 and showed the side population cell phenotype. COPs were multipotent with the ability to differentiate into adipocytes, chondrocytes, as well as neural cells, as shown by the expression of beta-III-tubulin, glial fibrillary acidic protein, and neurofilament-M. COP spheres prepared from E/nestin-enhanced green fluorescent protein (EGFP) mice showed induction of EGFP expression that was not originally observed in the cornea, indicating activation of the neural-specific nestin second intronic enhancer in culture. COPs were Sca-1(+), CD34(+), CD45(-), and c-kit(-). Numerous GFP(+) cells were observed in the corneas of mice transplanted with whole bone marrow of transgenic mice ubiquitously expressing GFP; however, no GFP(+) COP spheres were initiated from these mice. On the other hand, COP spheres from transgenic mice encoding P0-Cre/Floxed-EGFP as well as Wnt1-Cre/Floxed-EGFP were GFP(+), indicating the neural crest origin of COPs, which was confirmed by the expression of the embryonic neural crest markers Twist, Snail, Slug, and Sox9. Taken together, these data indicate the existence of neural crest-derived, multipotent stem cells in the adult cornea.
ATP Binding Cassette Transporter, Subfamily G, Mem↗
Proteomic analysis of soluble factors secreted by limbal fibroblasts.
PURPOSE: To identify soluble factors selectively secreted by limbal fibroblasts as possible regulators of limbal basal epithelium. METHODS: Limbal, corneal, and conjunctival fibroblasts were first expanded in vitro in Dulbecco's modified Eagle medium containing 10% fetal bovine serum, and then maintained in serum-free medium for two weeks. Proteomic analysis of culture supernatants was done to compare differences in secreted matricellular proteins. Real time PCR and western blots were done to confirm the expression of secreted protein acid and rich in cysteine (SPARC), a protein found in abundance in extracellular proteins secreted by limbal fibroblasts. Immunohistochemistry of SPARC was done in human limbal tissue to show the spatial distribution of the protein. An adhesion assay was designed to demonstrate the effects of SPARC on an SV40 immortalized human corneal epithelial cell line (HCEC). RESULTS: Proteomic analysis revealed several proteins selectively secreted by limbal fibroblasts. The particular spots were identified as SPARC, vimentin, serine protease, collagen alpha 2 precursor, tissue inhibitor of metalloproteinase 2 (TIMP-2), and 5,10-methlenetetrahdrofolate reductase (FADH2). The expression of SPARC was confirmed by western blot analysis, and mRNA expression was significantly higher in limbal fibroblasts compared to central corneal fibroblasts when analyzed by real time PCR. Immunohistochemistry revealed higher distribution of SPARC in the subepithelial stroma of the limbus compared to the central cornea. The addition of 10 microg/ml murine SPARC in HCEC significantly reduced cell spreading at three h. CONCLUSIONS: The matricellular protein SPARC is preferentially secreted by limbal fibroblasts, and may modulate intercellular adhesion of basal limbal epithelial cells.
Animals↗
Most patients with coronary artery calcification have no coronary artery stenosis and hyperphosphatemia should be important in reevaluating the K/DOQI guidelines.
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Calcinosis↗
Cytokeratin 15 can be used to identify the limbal phenotype in normal and diseased ocular surfaces.
PURPOSE: To elucidate the expression pattern of K15, K19, K14, and K12 in human and mouse ocular surface epithelium as putative markers of epithelial phenotype. METHODS: Immunohistochemical staining with specific antibodies for K15, K19, K14, and K12 was performed in human donor cornea tissue and normal ICR mouse corneas, with emphasis on localization of immunopositive cells. Immunohistochemistry was performed in a limbus-deficient mouse model as well as in clinical samples of pannus surgically removed from a thermal burn and a patient with Saltzmann's dystrophy. Staining patterns were classified as limited to the most basal layer (K(bas)), basal and suprabasal layers (K(bas-sup)), predominantly in suprabasal layers (K(sup)) and negative staining (K(-)). RESULTS: In human conjunctival epithelium, strong expression of K15 was observed in basal cells, whereas K19 was expressed in both basal and suprabasal layers (K15(bas)/K19(bas-sup)/K12(-)). Limbal epithelial cells were K15(bas-sup)/K19(bas-sup)/K12(sup), whereas epithelial cells in the central cornea were K15(-)/K19(bas-sup)/K12(bas-sup). In contrast, the mouse ocular surface demonstrated a different expression pattern of K15 and K19 than did the human tissue in the conjunctiva (K15(bas-sup)/K19(bas)/K12(-)) and the limbus (K15(bas-sup)/K19(bas)/K12(sup)). Neither K15 nor K19 was expressed in the central mouse cornea (K15(-)/K19(-)/K12(bas-sup)). Similar cytokeratin expression was observed in conjunctivalized corneas in mice and in surgically removed pannus tissue. CONCLUSIONS: Although the expression of K15 and K19 differ in humans and mice, specific staining patterns can be used to characterize the epithelial phenotype in normal and diseased ocular surface.
Animals↗
Effects of spironolactone during an angiotensin II receptor blocker treatment on the left ventricular mass reduction in hypertensive patients with concentric left ventricular hypertrophy.
BACKGROUND: Angiotensin II receptor blockers (ARB) are now commonly used to treat hypertension because of their beneficial effects on cardiovascular remodeling. However, ARB treatment can not inhibit the left ventricular (LV) remodeling sufficiently, which may be related with aldosterone secretion. To inhibit the action of aldosterone during ARB treatment, the additional effects of an aldosterone blocker and spironolactone (SPRL) on LV hypertrophy in patients with essential hypertension was studied. METHODS AND RESULTS: The patients with essential hypertension were randomly divided into 2 groups; 1 group was treated with an ARB, candesartan (8 mg/day), for 1 year (ARB group) and other group was treated with the ARB for the first 6 months and with the ARB plus SPRL (25 mg/day) for the next 6 months (combination group). Seventy patients who underwent echocardiography every 6 months were analyzed and were also classified into 4 subgroups of LV geometric pattern according to the LV mass index (LVMI) and the relative wall thickness (RWT). The ARB treatment and the addition of SPRL significantly reduced the blood pressure, however, both treatments did not affect the LV geometry in both groups. The ARB treatment in the subgroups of concentric LV remodeling (RWT>or=0.45 and LVMI<125) and concentric LV hypertrophy (RWT>or=0.45 and LVMI>or=125) significantly reduced RWT. However, ARB treatment in all subgroups did not affect LVMI. The addition of SPRL only in the concentric LV hypertrophy subgroup significantly reduced the LVMI, despite similar changes in blood pressure. CONCLUSIONS: These results indicated that the addition of SPRL treatment during the ARB treatment and conventional treatments is clinically useful to reduce the LVMI in hypertensive patients with concentric LV hypertrophy; however, does not improve the eccentric LV hypertrophy.
Aged↗
Investigation of coronary artery calcification and stenosis by coronary angiography (CAG) in haemodialysis patients.
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Adult↗
New diagnostic technique in multi-slice computed tomography for in-stent restenosis: pixel count method.
OBJECTIVES: A diagnostic technique to objectively determine coronary in-stent stenosis was developed with multi(16)-slice computed tomography (MSCT), and it was compared with coronary angiography (CAG) in clinical cases. BACKGROUND: MSCT is expected to replace coronary angiography as a new non-invasive examination. Evaluation of highly calcified or in-stent lesions with CT is generally thought to be difficult. METHODS: Twenty lesions among 16 consecutive patients that were implanted with coronary stents were examined with both MSCT and CAG at follow-up. The minor axis cross sections of the stents were reconstructed at intervals of 1.5 mm with multiplanar reformation (MPR). The pixel with a higher CT value than the lowest CT value in the standard cross section at the proximal site out of stent was counted to determine the presence/absence of a stenotic lesion. RESULTS: Among 20 lesions, one case was not able to be evaluated with MSCT. MSCT correctly detected 3 of 4 cases with in-stent stenosis (sensitivity 75%), and 14 of 16 cases with no in-stent stenosis (specificity 88%, negative predictive value 93%, positive predictive value 75%). If analysis was made per-artery, sensitivity and specificity were 100% (3 of 3) and 87% (13 of 15), respectively, for detection of in-stent stenosis. CONCLUSIONS: This study was performed to examine a unique diagnostic technique: pixel count method, for coronary in-stent stenosis with MSCT. It showed that the coronary in-stent stenosis could be determined when stent struts were clearly imaged. Further examination is required with various stents, especially those with a diameter of 3.0 mm or smaller.
Adult↗
Structure-activity relationship study on 13-deoxytedanolide, a highly antitumor macrolide from the marine sponge Mycale adhaerens.
To obtain information of structure-activity relationships (SARs) of 13-deoxytedanolide, its chemical transformation has been carried out, targeting on such functional groups as an epoxide, hydroxyls, ketones, and olefins. A total of 10 derivatives have been prepared and their cytotoxicity against P388 murine leukemia cells and inhibitory activity of polypeptide elongation in yeast cell lysate provided some important SARs; the southern hemisphere comprises the pharmacophore, while the epoxide-bearing side chain is essential for the activity.
Animals↗
Serum-free spheroid culture of mouse corneal keratocytes.
PURPOSE: To develop a serum-free mass culture system for mouse keratocytes. METHODS: Corneas of C57BL6/J mice were enzyme digested after the epithelium and endothelium were removed. Stromal cells were cultured in serum-free DMEM/F12 (1:1) containing epidermal growth factor (EGF), fibroblast growth factor 2 (FGF2), and B27 supplement. Primary spheres were dissociated by trypsin and subcultured as suspended secondary spheres. Cells from postnatal day (P)6 to P10 spheres were subcultured onto plastic dishes or type I collagen gels for phenotype analysis. The expression of the keratocyte markers keratocan, aldehyde dehydrogenase (Aldh), and CD34, were analyzed by RT-PCR, and vimentin and alpha-smooth muscle actin (alpha-SMA) were examined by immunocytochemistry. RESULTS: Primary keratocytes formed spheres, which were cultured for over 12 passages. Suspended sphere cells expressed vimentin, keratocan, CD34, and lumican, but were negative for cytokeratin K12 (K12) and Pax6. Sphere cells subcultured on plastic exhibited a dendritic morphology characteristic of keratocytes, and maintained keratocan, Aldh, and CD34 expression in serum-free medium. Sphere cells subcultured with 10% serum became fibroblastic, and expressed alpha-SMA when stimulated by transforming growth factor (TGF)-beta. alpha-SMA-positive cells demonstrated contractile properties on collagen gels, compatible with the myofibroblast phenotype. CONCLUSIONS: The phenotype of mouse keratocytes can be maintained in vitro for more than 12 passages by the serum-free sphere culturing technique.
Animals↗
Deteriorative effect of smoking on target lesion revascularization after implantation of coronary stents with diameter of 3.0 mm or less.
BACKGROUND: Although smoking cessation is widely encouraged because of the associated risk of cardiovascular events, the impact of smoking on target lesion revascularization (TLR) after percutaneous coronary intervention (PCI) is controversial. Therefore, the present study retrospectively investigated the effect of smoking on TLR after plain-old balloon angioplasty (POBA; n=376) and stenting (STENT; n=434) in patients undergoing secondary coronary angiography at a single center. METHODS AND RESULTS: A smoker was defined as current smoking or quitting within 2 years of the first PCI. In the POBA group, the predictors for TLR, as calculated by multiple logistic regression analysis, were a complex type of lesion (p<0.0001) and the left anterior descending artery (LAD) as affected vessel (p<0.05). In the STENT group, the predictors were the final % diameter of stenosis after stenting, measured by quantitative coronary arteriography (p<0.0005), LAD (p<0.01), and smoking (p=0.049). When the STENT group was divided into 2 groups according to the diameter of the implanted stent, smoking was a predictive factors for TLR in the group that received relatively small stents (diameter < or =3.0 mm) (p<0.02), but not in the group that received larger stents (diameter > or =3.5 mm). CONCLUSION: Smoking has a deteriorative effect on TLR after implantation of relatively small coronary stents with a diameter of 3.0 mm or less.
Angioplasty, Balloon, Coronary↗
JIKEI HEART Study--a morbi-mortality and remodeling study with valsartan in Japanese patients with hypertension and cardiovascular disease.
BACKGROUND: Several recent clinical trials have demonstrated that angiotensin II receptor blockers (ARBs) have cardiovascular as well as renal protective effects. Asian patients including Japanese were under-represented in these trials, however, and no large-scale clinical trials of ARBs have yet been performed in Japan. It is therefore important to verify that the results of these studies are also valid for Japanese patients. The JIKEI HEART Study has been designed to investigate whether concomitant treatment with valsartan, an angiotensin II receptor blocker, in addition to conventional treatment, will improve the prognosis of Japanese patients with cardiovascular diseases (hypertension, ischemic heart disease, congestive heart failure). METHOD AND EVALUATION OF RESULTS: Around 3,000 patients with hypertension, ischemic heart disease and/or congestive heart failure will be randomized to receive either additional treatment with valsartan (80 mg/day) or conventional therapy. The follow-up period will be three years. The primary endpoint will be the onset of any cardiovascular event. Secondary endpoints will include death from any cause, changes in left ventricular size and function, renal function, changes in neuro-hormonal levels and quality-of-life assessments. Sub-studies will explore the effect in patients with diabetes mellitus, hyperlipidemia and the effects of combination of drugs. CONCLUSION: Improved prognosis would confirm the role of angiotensin II receptor blockers in the treatment of the cardiovascular disease in Japanese patients.
Adult↗
A case report of late coronary stent thrombosis manifested as acute myocardial infarction 19 months after stenting.
A 63-year-old Japanese man was readmitted to our hospital due to acute broad-anterior myocardial infarction (AMI). The proximal left anterior descending artery (LAD) at the prior stent, which was implanted 19 months earlier and in which no angiographic restenosis was recognized 13 months before the second study, was totally occluded. After crossing a guide wire and balloon angioplasty, angiographic radiolucency was observed at the prior stent, suggesting that AMI was induced by late coronary stent thrombosis. Intravascular ultrasound performed 19 days after the onset of AMI revealed superficial calcification without significant stenosis and an atherosclerotic plaque distal to the stent that was not significantly changed compared to 19 months previously, consistent with the culprit lesion being an intrastent site. AMI may thus be induced by late coronary stent thrombosis during long-term clinical follow-up without clinical symptoms or angiographic restenosis at the second study.
Angioplasty, Balloon, Coronary↗
Usefulness of a 6 fr right judkins catheter for mechanically extracting a massive intracoronary thrombus from an ectasic right coronary artery: a report on two different cases of thrombectomy.
In order to bail out the slow-flow phenomenon (slow flow) created by a massive thrombus in an ectasic right coronary artery, a thrombus was mechanically extracted with a 6 Fr right Judkins (JR) catheter, which proved to be more useful than a usual thrombectomy using a Rescue PT system catheter (Rescue). In case 1, the Rescue was used in combination with thrombolysis but failed to alleviate the slow flow that was implicated in a large infarction. On the other hand, in case 2, aggressive thrombectomy with a 6 Fr JR catheter with an 8 Fr Amplatz guiding catheter successfully extracted the massive intracoronary thrombus, restoring good coronary flow. Therefore, mechanical extraction with a 6 Fr JR catheter is safe and useful in cases of massive thrombus when diffuse coronary artery ectasia complicates an acute myocardial infarction. In addition, this method should be applicable to cases of acute coronary syndrome with massive thrombus.
Adult↗
A lethal complication of central venous catheterisation.
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Catheterization, Central Venous↗
Thoracic involvement of type A aortic dissection and intramural hematoma: diagnostic accuracy--comparison of emergency helical CT and surgical findings.
PURPOSE: To assess the accuracy of various findings at emergency helical computed tomography (CT) for the evaluation of thoracic involvement of type A aortic dissection (AD) and type A intramural hematoma (IMH) and to compare these findings with those at surgical confirmation. MATERIALS AND METHODS: Fifty-seven patients with acute chest pain underwent emergency helical CT and subsequent surgery for type A AD or IMH. Patients in whom AD or IMH was detected in three segments of the thoracic aorta or those in whom there was a site of any entry tear, arch branch vessel involvement, pericardial effusion, or aortic arch anomaly were examined at helical CT. Sensitivity, specificity, and accuracy of helical CT, along with 95% CIs, were calculated by using surgical confirmation as the reference standard. RESULTS: For the detection of AD or IMH of the thoracic aorta, the accuracy of helical CT was 100%. The sensitivity, specificity, and accuracy, respectively, were 82%, 100%, and 84% for an entry tear; 95%, 100%, and 98% for arch branch vessel involvement; and 83%, 100%, and 91% for pericardial effusion. These values were all 100% for aortic arch anomalies. CONCLUSION: Emergency helical CT of the thorax depicts findings that are highly accurate in the evaluation of acute type A AD and IMH.
Adult↗
The empty delta sign.
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Cerebral Angiography↗