Early progressive infarction (EPI) is frequently observed and related to poor functional outcome in patients with middle cerebral artery (MCA) infarction caused by MCA occlusion. We evaluated the ...perfusion parameters of magnetic resonance imaging (MRI) as a predictor of EPI.
We retrospectively analyzed patients with acute MCA territory infarction caused by MCA occlusion. EPI was defined as a National Institutes of Health Stroke Scale increment ≥2 points during 24 hours despite receiving standard treatment. Regional parameter ratios, such as cerebral blood flow and volume (rCBV) ratio (ipsilateral value/contralateral value) on perfusion MRI were analyzed to investigate the association with EPI.
Sixty-four patients were enrolled in total. EPI was present in 18 (28%) subjects and all EPI occurred within 3 days after hospitalization. Diabetes mellitus, rCBV ratio and regional time to peak (rTTP) ratio showed statically significant differences in both groups. Multi-variate analysis indicated that history of diabetes mellitus odds ratio (OR), 6.13; 95% confidence interval (CI), 1.55-24.24 and a low rCBV ratio (rCBV, <0.85; OR, 6.57; 95% CI, 1.4-30.27) was significantly correlated with EPI.
The incidence of EPI is considerable in patients with acute MCA territory infarction caused by MCA occlusion. We suggest that rCBV ratio is a useful neuro-imaging parameter to predict EPI.
Due to their capability of modifying chromatin structure and thereby regulating gene transcription, histone deacetylases (HDACs) have been reported to play important roles in osteogenesis and ...considered a promising potential therapeutic target for bone diseases, including osteoporosis. We showed that the novel marine-derived HDAC inhibitor largazole exhibits in vitro and in vivo osteogenic activity. Largazole significantly induced the expression of ALP and OPN. The osteogenic activity of largazole was mediated through the increased expression of Runx2 and BMPs. Importantly, largazole showed in vivo bone-forming efficacy in the mouse calvarial bone formation assay and the rabbit calvarial bone fracture healing model. The dual action of largazole to stimulate bone formation and inhibit bone resorption would be a useful feature in drug development for bone-related disorders.
TALLYHO/Jng (TH) mice reveal hypercholesterolemia at an early age before their plasma glucose levels have increased. The increased plasma cholesterol should be related to bile acids (BAs) metabolism, ...because cholesterol is the precursor of BAs and BAs change cholesterol metabolism in a feedback manner. We analyzed the BAs pool size, BAs composition, and expression levels of several proteins that have key roles in BAs synthesis, excretion, and reabsorption and compared them to those of C57BL/6 (B6) mice to study BAs metabolism in TH mice. TH mice exhibited an increased total BAs pool size, increased BAs content in the cecum feces, and an increased ratio of muricholic acid (MCA)/cholic acid (CA). The mRNA and protein levels of cholesterol 7 alpha-hydroxylase (Cyp7a1) and the ATP-binding cassette sub-family G member 5 (Abcg5) were elevated in the liver but not in the apical sodium bile acid transporter (Asbt) and organic solute transporters (Osts) in the ileum. These results indicate that synthesis and the excretion of BAs from the liver to the gallbladder might be elevated, but the reabsorption rate of BAs in the ileum might be reduced. The declined expression of fibroblast growth factor 15 (Fgf15) and fibroblast growth factor receptor 4 (Fgfr4) was respectively identified in the ileum and the liver, indicating the disrupted feedback inhibition of Cyp7a1. Consequently, hypercholesterolemia in TH mice might increase the BAs amounts via the interrupted Fxr/Fgf15/Fgfr4-mediated feedback regulation of Cyp7a1.
•TH mice have increased total BAs pool size in enterohepatic circulation.•Increased the mRNA and protein levels of Cyp7a1 in the liver•Declined levels of Fgf15 and Fgfr4 in the ileum and liver•Hypercholesterolemia might increase BAs via disrupted Fxr-mediated feedback regulation of Cyp7a1 in TH mice.
Due to the high reactivity of the formyl group under either basic or acidic reaction conditions required for the direct generation of aldehyde enolates, intramolecular Michael additions of aldehyde ...enolates to α,β-unsaturated carbonyl compounds have been underexplored for the stereoselective synthesis of carbocyclic compounds. The intramolecular Michael reaction of aldehyde enolates generated by imidazolium carbenes was explored for the synthesis of cyclopentane aldehydes. The imidazolium carbenes were used as Brønsted bases to directly generate the aldehydes enolates.
Nanostructured titanium dioxide (NTiO
2
) is known to possess efficient photocatalytic activity and to have diverse applications in many fields due to its chemical stability, high surface area/volume ...ratio, high transmittance, and high refractive index in the visible and the near-ultraviolet regions. These facts prompted us to develop TiO
2
nanotube (TiO
2
NT) arrays through electrochemical anodic oxidation involving different electrolytes comprised of phosphoric acid — hydrofluoric acid aqueous systems by varying the voltage and the time. The annealing temperature of the nanotubes, TiO
2
NTs, were varied to modify the surface morphology and were characterized by using X-ray diffraction and scanning electron microscopy. Scanning electron microscopy and X-ray diffraction results showed that the samples had uniform morphologies and good crystalline structures of the anatase phase at lower annealing temperatures and of the rutile phase at higher annealing temperatures. A secondary-ion mass-spectrometry analysis was used to investigate the surface atoms and to conduct a depth profile analysis of the TiO
2
NTs. The efficiency of the photocatalytic activity of the TiO
2
NT arrays in degrading methylene blue (MB) was investigated under UV-Vis light irradiation. The maximum photocatalytic activity was achieved for the samples with lower annealing temperatures due to their being in the anatase phase and having a higher surface area and a smaller crystal size, which play important roles in the degradation of organic pollutants.
Purpose Eukaryotic translation initiation factor 4E (eIF4E) is overexpressed in many cancer and is emerging as a potential therapeutic target. Yet data on the expression of eIF4E in endometrial ...cancer are lacking. Methods Immunohistochemistry was used to evaluate the expression of eIF4E in 62 endometrial cancer surgical specimens. We subsequently evaluated whether inhibition of eIF4E by siRNA would have an impact on cell growth in endometrial cancer cell lines, using the MTT cell proliferation assay. Results According to a chosen cutoff value, 36 (58.1%) of 62 patient specimens scored as eIF4E positive. The positivity of eIF4E was significantly more frequent in tumors extending outside the uterus (stage III/IV vs. stage I/II, P = 0.027). Lastly, downregulation of eIF4E by siRNA reduced the growth of HEC-1A cells significantly but had a somewhat weaker effect in Ishikawa cells (P < 0.001). Conclusions Expressions of eIF4E correlated with prognosis of endometrial adenocarcinomas. Our results suggest that eIF4E might be a promising therapeutic target in endometrial cancer.
The authors report two cases of stent fracture and restenosis after placement of a drug-eluting device in the vertebral artery (VA) origin, and describe management of restenosis with the ...stent-in-stent technique. Two women, one 62 and the other 67 years of age, underwent stent placement in the VA origin to treat symptomatic and angiographically significant stenosis in this vessel. Sirolimus-eluting coronary stents (Cypher) were used in both cases. Four months after placement of the devices, the symptoms recurred. Follow-up angiography performed 5 months after insertion of the devices revealed a transverse stent fracture with separation of the fragments and severe in-stent restenosis in both cases. The restenoses were treated with reinsertion of coronary stents (Cypher and Jostent FlexMaster) by using the stent-in-stent technique. After stent reinsertion, the patients exhibited relief of symptoms. This paper is the first report of fracture in a drug-eluting stent and restenosis after stent placement in the VA origin. Restenosis caused by such a fracture can be managed successfully by performing the stent-in-stent maneuver. The physical properties of metallic devices, stent strut geometry, and anatomical peculiarities of the subclavian artery may be associated with stent fractures. Earlier follow-up angiography studies (within 6 months) are warranted.
Clinicopathological features of four cases of oncocytic adrenocortical carcinomas were studied. All tumors were large, circumscribed tumors with average size and weight of 11.5 cm and 586 g, ...respectively. The cut surfaces were yellow or brown and tan with areas of hemorrhage, necrosis, fibrosis, myxoid and cystic change. The tumor cells were exclusively oncocytic with a diffuse or compact and solid arrangement. Nuclear atypia was identified but mitosis was rare. Capsular invasion was identified in all tumors and vascular invasion was identified in one tumor. All tumors were immunoreactive for vimentin and inhibins. Immunoreactivity for pancytokeratin, synaptophysin and S‐100 protein was variable and focal. All tumors had low proliferative indices, of less than 1%, and were negative for p53 protein. Ultrastructurally, the cytoplasm of tumor cells showed numerous mitochondria in a compact arrangement. Oncocytic adrenocortical carcinomas showed a similar sex ratio, slightly older mean age, similar left predilection, slightly smaller size and lighter weight compared with the conventional carcinomas. We suggest that most oncocytic adrenocortical carcinomas might be low‐grade malignancies with less aggressive histological features compared with conventional carcinomas. However, they should be excised completely because of the likelihood of recurrence and metastasis during the follow‐up period.
Even though p16(INK4a) (p16) immunocytochemistry has proven a useful accessory tool verifying the identification of atypical squamous cells of undetermined significance (ASC-US) categorized smears, ...the procedure still has limitations. To date few studies examining the usefulness of p16 immunocytochemistry in atypical squamous cells which cannot exclude HSIL (ASC-H), compared with ASC-US in liquid-based cervical smears. Therefore, we examined the correlation of p16 immunocytochemical staining with follow-up biopsy results on ASC-H categorized smears and compared the data with those classified as ASC-US on 105 liquid-based cytology samples. We found no statistical significance in the p16 expression of ASC-US smears and the presence of squamous intraepithelial lesions (SIL) in follow-up biopsies (p = 0.546). However, p16 expression did significantly correlate with the presence of SIL (p = 0.002) in ASC-H smears. There was a statistically significant relationship between p16 expression and presence of high grade squamous intraepithelial lesions (HSIL) or more on the follow-up biopsies in both ASC-US (p = 0.012) and ASC-H (p < 0.001) categorized smears. In ASC-US categorized smears, there was no statistical significance between p16 expression and the HR-HPV viral load (p = 0.091). But there was a statistical significance between p16 expression and the HR-HPV viral load (p < 0.001) in ASC-H categorized smears. Our results indicate that p16 immunostaining is a much better useful marker for HR-HPV infection and detection of SIL in ASC-H categorized smears compared to those defined as ASC-US.
Abstract Objective Endometrial adenocarcinoma has been proposed, due to frequent activation of the PI3K/AKT pathway, as a candidate neoplasm for treatment with mTOR inhibitors. However, data on the ...expression of mTOR in endometrial cancer are lacking. Study design We used immunohistochemistry to evaluate the expression of pmTOR in 62 endometrial cancer surgical specimens. Results The pmTOR protein was diffusely expressed in the cytoplasm of neoplastic epithelial cells, showing variable intensity. According to the chosen cutoff value, 34 (54.8%) out of 62 patients were scored as pmTOR-positive. pmTOR expression was significantly decreased in carcinomas with deep infiltration into the myometrium ( P = .009), though it was not correlated with disease stage or lymph node metastasis. Univariate analysis showed that increased expression of pmTOR was significantly associated with better disease-free survival ( P = .021). Conclusions We show for the first time an association between pmTOR and better survival in patients with endometrial cancer. Future studies to stratify endometrial tumors by pmTOR status are needed.
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