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1.
Proc Natl Acad Sci U S A ; 121(27): e2406946121, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38917015

ABSTRACT

Progerin, the protein that causes Hutchinson-Gilford progeria syndrome, triggers nuclear membrane (NM) ruptures and blebs, but the mechanisms are unclear. We suspected that the expression of progerin changes the overall structure of the nuclear lamina. High-resolution microscopy of smooth muscle cells (SMCs) revealed that lamin A and lamin B1 form independent meshworks with uniformly spaced openings (~0.085 µm2). The expression of progerin in SMCs resulted in the formation of an irregular meshwork with clusters of large openings (up to 1.4 µm2). The expression of progerin acted in a dominant-negative fashion to disrupt the morphology of the endogenous lamin B1 meshwork, triggering irregularities and large openings that closely resembled the irregularities and openings in the progerin meshwork. These abnormal meshworks were strongly associated with NM ruptures and blebs. Of note, the progerin meshwork was markedly abnormal in nuclear blebs that were deficient in lamin B1 (~50% of all blebs). That observation suggested that higher levels of lamin B1 expression might normalize the progerin meshwork and prevent NM ruptures and blebs. Indeed, increased lamin B1 expression reversed the morphological abnormalities in the progerin meshwork and markedly reduced the frequency of NM ruptures and blebs. Thus, progerin expression disrupts the overall structure of the nuclear lamina, but that effect-along with NM ruptures and blebs-can be abrogated by increased lamin B1 expression.


Subject(s)
Lamin Type A , Lamin Type B , Nuclear Lamina , Nuclear Lamina/metabolism , Lamin Type A/metabolism , Lamin Type A/genetics , Lamin Type B/metabolism , Lamin Type B/genetics , Humans , Progeria/metabolism , Progeria/genetics , Progeria/pathology , Animals , Protein Precursors/metabolism , Protein Precursors/genetics , Myocytes, Smooth Muscle/metabolism , Myocytes, Smooth Muscle/pathology , Mice
2.
Eur J Clin Microbiol Infect Dis ; 36(8): 1473-1481, 2017 Aug.
Article in English | MEDLINE | ID: mdl-28337607

ABSTRACT

Persistent bacteraemia (PB) due to methicillin-resistant Staphylococcus aureus (MRSA) that fails to respond to glycopeptide therapy is a well-documented clinical problem. There are limited data on changes in agr functionality, vancomycin susceptibility and heteroresistance during MRSA PB. Thus, the frequency of these changes and their clinical significance remain unclear. Only patients with MRSA PB (≥7 days) from a prospective cohort of S. aureus bacteraemia were included. We collected isogenic paired strains and compared vancomycin MIC, vancomycin heteroresistance, and agr functionality between initial and final blood isolates. We also assessed the clinical outcome. A total of 49 patients had MRSA PB over 22 months. Bacteraemia persisted for a median of 13 days and most patients (98%) received glycopeptide as initial therapy. Among 49 isogenic pairs, only one pair showed a vancomycin MIC increase ≥2-fold by broth microdilution method, and only seven (14%) by E-test. Significant portions of initial isolates had vancomycin heteroresistance (49%) and agr dysfunction (76%). Development of vancomycin heteroresistance during PB occurred in four (16%) among 25 initial vancomycin-susceptible isolates, and acquisition of agr dysfunction occurred in two (16%) among 12 initial agr-functional isolates. Changes in the opposite direction occasionally occurred. These phenotypic changes during PB were not associated with mortality, whereas agr dysfunction of the initial isolates was significantly associated with mortality. During MRSA PB, phenotypic changes of MRSA isolates occurred occasionally under prolonged vancomycin exposure but were not significantly associated with clinical outcome. In contrast, initial agr dysfunction could be a predictor for mortality in MRSA PB.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Bacteremia/drug therapy , Methicillin-Resistant Staphylococcus aureus/drug effects , Methicillin-Resistant Staphylococcus aureus/physiology , Phenotype , Staphylococcal Infections/drug therapy , Vancomycin/therapeutic use , Adolescent , Adult , Aged , Aged, 80 and over , Bacteremia/microbiology , Bacteremia/mortality , Bacterial Proteins/metabolism , Female , Humans , Male , Methicillin-Resistant Staphylococcus aureus/classification , Methicillin-Resistant Staphylococcus aureus/isolation & purification , Microbial Sensitivity Tests , Middle Aged , Prospective Studies , Staphylococcal Infections/microbiology , Staphylococcal Infections/mortality , Survival Analysis , Trans-Activators/metabolism , Treatment Outcome , Young Adult
3.
Transplant Proc ; 48(6): 2192-9, 2016.
Article in English | MEDLINE | ID: mdl-27569970

ABSTRACT

BACKGROUND: It has been reported that nafamostat mesilate (NM) inhibits inflammatory injury via inhibition of complement activation in ischemic heart, liver, and intestine. However, it is unclear if NM also inhibits apoptosis in ischemia-reperfusion (IR)-injured kidney. We therefore investigated whether NM attenuates IR renal injury that involves inhibition of apoptosis. METHODS: HK-2 cells and male C57BL/6 mice were used for this study. C57Bl/6 mice were divided into 4 groups: sham, NM (2 mg/kg) + sham, IR injury (IR injury; reperfusion 27 minutes after clamping of both the renal artery and vein), and NM + IR injury. Kidneys were harvested 24 hours after IR injury, and functional and molecular parameters were evaluated. For in vitro studies, HK-2 cells were incubated for 6 hours with mineral paraffin oil to induce hypoxic injury, and then treated with various doses of NM to evaluate the antiapoptotic effects. RESULTS: Blood urea nitrogen, serum creatinine levels, and renal tissue injury scores in NM + IR-injured mice were significantly lower than those of control IR mice (all P < .01). NM significantly improved cell survival in hypoxic HK-2 cells (P < .01), significantly decreased renal Bax expression (P < .05), and increased renal Bcl-2 protein levels in IR kidneys and hypoxic HK-2 cells compared with those of the sham and control groups. The numbers of terminal deoxynucleotide transferase-mediated dUTP nick-end labeling- and 8-oxo-2'-deoxyguanosine-positive cells were significantly lower in NM + IR-injured kidneys compared with those in control IR-injured mice (P < .05); NM treatment decreased the expression of inducible and endothelial nitric oxide synthase in IR-injured mice (P < .05). CONCLUSIONS: NM ameliorates IR renal injury via inhibition of apoptosis by, at least in part, lowering nitric oxide overproduction, reducing Bax, and increasing Bcl-2.


Subject(s)
Acute Kidney Injury/prevention & control , Anticoagulants/administration & dosage , Guanidines/administration & dosage , Ischemic Preconditioning/methods , Kidney/blood supply , Reperfusion Injury/prevention & control , 8-Hydroxy-2'-Deoxyguanosine , Animals , Apoptosis/drug effects , Benzamidines , Blood Urea Nitrogen , Deoxyguanosine/analogs & derivatives , Disease Models, Animal , In Situ Nick-End Labeling , Kidney/drug effects , Male , Mice , Mice, Inbred C57BL , Nitric Oxide Synthase Type III/metabolism , Renal Artery/drug effects , Renal Artery/injuries
4.
Transplant Proc ; 48(1): 199-204, 2016.
Article in English | MEDLINE | ID: mdl-26915868

ABSTRACT

Renal ischemia-reperfusion injury (IRI) is involved in multiple diseases, such as kidney transplantation or contrast-induced nephropathy, and leads to acute kidney injury. However, there are no pharmacological agents available to prevent IRI. In this study, we investigated the effects of necroX-7 against renal IRI in a rat model. Seven-week-old male Sprague-Dawley rats were divided into four groups: saline-treated sham or IRI group, necroX-7-treated sham or IRI group. All animals had right nephrectomy and IRI was followed by reperfusion after clamping the left renal vessels for 35 minutes. NecroX-7 or saline was intravenously injected at 5 minutes before reperfusion. The effects of necroX-7 on IRI were evaluated using biochemical, histological, and molecular markers. The serum creatinine level was increased after IRI compared with sham. The necroX-7 significantly decreased creatinine level compared with the saline in IRI (1.36 ± 0.11 vs 2.35 ± 0.42 mg/dL; P < .05). An immunohistochemical study revealed that necroX-7 improved renal tubular injury, and attenuated 8-OHdG-positive cells (P < .001) and high-mobility group Box 1 protein (HMGB1) expression compared with saline treatment in IRI (P < .001). NecroX-7 significantly reduced monocyte chemoattractant protein 1 (MCP-1), tumor necrosis factor (TNF)-α, and interleukin (IL)-1ß in IRI (necroX-7-treated IRI vs saline-treated IRI rats; 1.73 ± 0.42 vs 7.23 ± 0.54-fold for MCP-1, P < .05; 0.79 ± 0.59 vs 3.72 ± 0.37-fold for TNF-α, P < .05; 0.50 ± 0.36 vs 2.43 ± 0.41-fold for IL-1ß, P < .001). In conclusion, necroX-7 improved renal dysfunction after IRI. These effects of necroX-7 occurred with the suppression of reactive oxygen species, HMGB1, and inflammatory responses. We suggest that necroX-7 has potential therapeutic benefits in renal IRI.


Subject(s)
Kidney/blood supply , Organic Chemicals/pharmacology , Reperfusion Injury/prevention & control , Animals , HMGB1 Protein/metabolism , Interleukin-1beta/metabolism , Kidney/surgery , Kidney Transplantation/adverse effects , Male , Necrosis , Nephrectomy/adverse effects , Rats , Rats, Sprague-Dawley , Reactive Oxygen Species/metabolism , Reperfusion Injury/etiology , Tumor Necrosis Factor-alpha/metabolism
5.
AJNR Am J Neuroradiol ; 37(4): 686-91, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26542236

ABSTRACT

BACKGROUND AND PURPOSE: Carotid artery stent placement in patients with intraplaque hemorrhage remains controversial because of the incidence of cerebral embolism after the procedure. The purpose of this study is to determine if intraplaque hemorrhage is a significant risk factor for cerebral embolism during carotid artery stent placement. MATERIALS AND METHODS: This prospective study assessed 94 consecutive patients with severe carotid stenosis. These patients underwent preprocedural carotid MR imaging and postprocedural DWI after carotid artery stent placement. Intraplaque hemorrhage was defined as the presence of high signal intensity within the carotid plaque that was >200% of the signal from the adjacent muscle on MPRAGE. We then analyzed the incidence of postprocedural ipsilateral ischemic events on DWI and primary outcomes within 30 days of carotid artery stent placement. RESULTS: Forty-three patients (45.7%) had intraplaque hemorrhage on an MPRAGE image. There was no significant difference in the incidence of postprocedural ipsilateral ischemic events and primary outcomes between the intraplaque hemorrhage and non-intraplaque hemorrhage group. However, postprocedural ipsilateral ischemic events were more frequently observed in the symptomatic group (17/41 [41.5%]) than in the asymptomatic group (8/53 [15.1%]; P = .005). CONCLUSIONS: Intraplaque hemorrhage was not a significant risk factor for cerebral embolism during carotid artery stent placement in patients with severe carotid stenosis. Symptomatic patients should receive more careful treatment during carotid artery stent placement because of the higher risk of postprocedural ipsilateral ischemic events.


Subject(s)
Carotid Arteries/surgery , Carotid Artery Diseases/complications , Cerebral Hemorrhage/complications , Intracranial Embolism/complications , Plaque, Atherosclerotic/complications , Stents/adverse effects , Aged , Aged, 80 and over , Carotid Artery Diseases/diagnostic imaging , Carotid Stenosis/surgery , Cerebral Hemorrhage/diagnostic imaging , Diffusion Magnetic Resonance Imaging , Female , Humans , Image Processing, Computer-Assisted , Intracranial Embolism/diagnostic imaging , Male , Middle Aged , Plaque, Atherosclerotic/diagnostic imaging , Prospective Studies , Risk Factors , Treatment Outcome
6.
Andrologia ; 48(6): 654-61, 2016 Aug.
Article in English | MEDLINE | ID: mdl-26589369

ABSTRACT

Recent meta-analysis by the Cochrane collaboration concluded that treatment of varicocele may improve an infertile couple's chance of pregnancy. However, there has been no consensus on the management of subclinical varicocele. Therefore, we determine the impact of varicocele treatment on semen parameters and pregnancy rate in men with subclinical varicocele. The randomised controlled trials that assessed the presence and/or treatment of subclinical varicocele were included for systematic review and meta-analysis. Random effect model was used to calculate the weighted mean difference of semen parameters and odds ratio of pregnancy rates. Seven trials with 548 participants, 276 in subclinical varicocelectomy and 272 in no-treatment or clomiphene citrate subjects, were included. Although there was also no statistically significant difference in pregnancy rate (OR 1.29, 95% CI 0.99-1.67), surgical treatment resulted in statistically significant improvements on forward progressive sperm motility (MD 3.94, 95% CI 1.24-6.65). However, the evidence is not enough to allow final conclusions because the quality of included studies is very low and further research is needed.


Subject(s)
Infertility, Male/surgery , Varicocele/surgery , Vascular Surgical Procedures , Female , Humans , Infertility, Male/etiology , Male , Pregnancy , Pregnancy Rate , Severity of Illness Index , Treatment Outcome , Varicocele/complications , Varicocele/diagnosis
7.
Bone Joint J ; 97-B(10): 1364-9, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26430011

ABSTRACT

Macrodactyly of the foot is a rare but disabling condition. We present the results of surgery on 18 feet of 16 patients, who underwent ray amputation and were followed-up for more than two years at a mean of 80 months (25 to 198). We radiologically measured the intermetatarsal width and forefoot area pre-operatively and at six weeks and two years after surgery. We also evaluated the clinical results using the Oxford Ankle Foot Questionnaire for children (OxAFQ-C) and the Questionnaire for Foot Macrodactyly. The intermetatarsal width and forefoot area ratios were significantly decreased after surgery. The mean OxAFQ-C score was 42 (16 to 57) pre-operatively, improving to 47 (5 to 60) at two years post-operatively (p = 0.021). The mean questionnaire for Foot Macrodactyly score two years after surgery was 8 (6 to 10). Ray amputation gave a measurable reduction in foot size with excellent functional results. For patients with metatarsal involvement, a motionless toe, or involvement of multiple digits, ray amputation is a clinically effective option which is acceptable to patients.


Subject(s)
Amputation, Surgical/methods , Foot Deformities, Congenital/surgery , Adolescent , Child , Child, Preschool , Female , Follow-Up Studies , Foot Deformities, Congenital/diagnostic imaging , Humans , Infant , Male , Radiography , Surveys and Questionnaires , Time Factors , Treatment Outcome
8.
Ann Oncol ; 26(6): 1142-1148, 2015 Jun.
Article in English | MEDLINE | ID: mdl-25716425

ABSTRACT

BACKGROUND: MicroRNAs (miRNAs) have a key role in carcinogenesis through negative regulation of their target genes. Therefore, genetic variations in miRNAs or their target sites may affect miRNA-mRNA interactions, thereby result in altered expression of target genes. This study was conducted to investigate the associations between single-nucleotide polymorphisms (SNP) located in the miRNA target sites (poly-miRTSs) and survival of patients with early-stage non-small-cell lung cancer (NSCLC). METHODS: Using public SNP database and miRNA target sites prediction program, 354 poly-miRTSs were selected for genotyping. Among these, 154 SNPs applicable to Sequenom's MassARRAY platform were investigated in 357 patients. A replication study was carried out on an independent patient population (n = 479). Renilla luciferase assay and reverse transcription-polymerase chain reaction were conducted to examine functional relevance of potentially functional poly-miRTSs. RESULTS: Of the 154 SNPs analyzed in a discovery set, 14 SNPs were significantly associated with survival outcomes. Among these, KRT81 rs3660G>C was found to be associated with survival outcomes in the validation cohort. In the combined analysis, patients with the rs3660 GC + CC genotype had a significantly better overall survival compared with those with GG genotype [adjusted hazard ratio (aHR) for OS, 0.65; 95% confidence interval (CI) 0.50-0.85; P = 0.001]. An increased expression of the reporter gene for the C allele of rs3660 compared with the G allele was observed by luciferase assay. Consistently, the C allele was associated with higher relative expression level of KRT81 in tumor tissues. CONCLUSION: The rs3660G>C affects KRT81 expression and thus influences survival in early-stage NSCLC. The analysis of the rs3660G>C polymorphism may be useful to identify patients at high risk of a poor disease outcome.


Subject(s)
Carcinoma, Non-Small-Cell Lung/genetics , Keratins, Hair-Specific/genetics , Keratins, Type II/genetics , Lung Neoplasms/genetics , MicroRNAs/genetics , Polymorphism, Single Nucleotide , 3' Untranslated Regions , Aged , Binding Sites , Carcinoma, Non-Small-Cell Lung/metabolism , Carcinoma, Non-Small-Cell Lung/mortality , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/therapy , Computational Biology , Databases, Genetic , Female , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Gene Frequency , Genetic Predisposition to Disease , HEK293 Cells , Humans , Kaplan-Meier Estimate , Keratins, Hair-Specific/metabolism , Keratins, Type II/metabolism , Lung Neoplasms/metabolism , Lung Neoplasms/mortality , Lung Neoplasms/pathology , Lung Neoplasms/therapy , Male , MicroRNAs/metabolism , Middle Aged , Neoplasm Staging , Phenotype , Proportional Hazards Models , RNA, Messenger/genetics , RNA, Messenger/metabolism , Risk Factors , Time Factors , Transfection
9.
Eur J Clin Microbiol Infect Dis ; 34(2): 349-55, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25213722

ABSTRACT

Cefazolin treatment failures have been described for bacteraemia caused by methicillin-susceptible Staphylococcus aureus (MSSA) with type A ß-lactamase and inoculum effect (InE). We investigated the prevalence of blaZ (ß-lactamase) gene types and a cefazolin InE among MSSA blood isolates in South Korea and evaluated their association with specific genotypes. The clinical impact of the cefazolin InE was also evaluated. A total of 220 MSSA isolates were collected from a prospective cohort study of S. aureus bacteraemia. A pronounced InE with cefazolin was defined as a ≥4-fold increase in the minimum inhibitory concentration (MIC) between a standard and high inoculum, resulting in a non-susceptible MIC. Sequencing of blaZ and multilocus sequence typing (MLST) were performed. Clinical outcomes were assessed in 77 patients treated with cefazolin. The blaZ gene was detected in 92 % of the 220 MSSA isolates. Type C ß-lactamase was the most common (53 %), followed by type B (20 %) and type A (17 %). Certain genotypes were significantly associated with specific ß-lactamase types (notably, ST30 and type A ß-lactamase). A pronounced cefazolin InE was observed in 13 % of isolates. Most of these (79 %) expressed type A ß-lactamase and ST30 was the predominant (55 %) clone amongst them. Cefazolin treatment failure was not observed in patients infected with strains exhibiting a pronounced InE. These strains had no impact on other clinical outcomes. In conclusion, the prevalence of a pronounced InE with cefazolin could be dependent upon distributions of MSSA genotypes. Cefazolin can likely be used for the treatment of MSSA bacteraemia (except endocarditis), without consideration of an InE.


Subject(s)
Anti-Bacterial Agents/pharmacology , Cefazolin/pharmacology , Staphylococcal Infections/epidemiology , Staphylococcus aureus/isolation & purification , beta-Lactamases/genetics , Aged , Bacteremia , Bacterial Typing Techniques , Cohort Studies , Female , Genotype , Humans , Male , Methicillin/pharmacology , Microbial Sensitivity Tests , Middle Aged , Multilocus Sequence Typing , Prevalence , Prospective Studies , Republic of Korea/epidemiology , Staphylococcal Infections/drug therapy , Staphylococcal Infections/microbiology , Staphylococcus aureus/classification , Staphylococcus aureus/drug effects , Staphylococcus aureus/genetics , Treatment Outcome
10.
J Endocrinol Invest ; 37(2): 167-73, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24497215

ABSTRACT

BACKGROUND: Pathologically confirmed microscopic extrathyroidal extension (ETE) is often identified after hemithyroidectomy in patients with papillary thyroid microcarcinoma (PTMC). Without the presence of microscopic ETE, these patients would be optimal candidates for hemithyroidectomy. AIM: The present study aimed at evaluating the clinical impact of microscopic ETE on the recurrence of PTMC treated with hemithyroidectomy. SUBJECTS AND METHODS: We compared the clinicopathological characteristics and 5-year outcomes for 262 PTMC patients without ETE and 86 with microscopic ETE who were treated with hemithyroidectomy between January 2004 and December 2010. RESULTS: The mean tumour size was larger (0.67 vs. 0.54 cm, p < 0.001) and the proportion of tumours measuring ≥0.5 cm was higher (84.9 vs. 66.8 %, p = 0.001) in patients with microscopic ETE as compared with patients without ETE. Occult multifocal disease was more frequent in patients with microscopic ETE than in those without ETE (14.0 vs. 6.5 %, p = 0.030). However, the recurrence rate was not different between the two groups during the mean 55.8-month follow-up period. In addition, univariate and multivariate analyses revealed no meaningful association between recurrence and microscopic ETE in patients with PTMC treated with hemithyroidectomy. CONCLUSIONS: Although microscopic ETE was associated with large tumour size and multifocal disease, its clinical impact on disease recurrence was not significant in PTMC patients treated with hemithyroidectomy. Therefore, microscopic ETE identified after hemithyroidectomy would not be an absolute indication for completion thyroidectomy in patients with PTMC.


Subject(s)
Carcinoma, Papillary/diagnosis , Carcinoma, Papillary/pathology , Carcinoma, Papillary/surgery , Neoplasm Recurrence, Local/diagnosis , Thyroid Neoplasms/diagnosis , Thyroid Neoplasms/pathology , Thyroid Neoplasms/surgery , Thyroidectomy/methods , Adult , Carcinoma, Papillary/epidemiology , Female , Humans , Male , Middle Aged , Neoplasm Invasiveness , Neoplasm Metastasis , Neoplasm Recurrence, Local/epidemiology , Neoplasm Recurrence, Local/pathology , Prognosis , Retrospective Studies , Thyroid Neoplasms/epidemiology , Treatment Outcome , Tumor Burden
11.
J Anim Physiol Anim Nutr (Berl) ; 98(1): 149-57, 2014 Feb.
Article in English | MEDLINE | ID: mdl-23441935

ABSTRACT

Dietary lysine restriction may differentially affect body growth and lipid and nitrogen metabolism, depending on the degree of lysine restriction. This study was conducted to examine the effect of dietary lysine restriction on growth and lipid and nitrogen metabolism with two different degree of lysine restriction. Isocaloric amino acid-defined diets containing 1.4% lysine (adequate), 0.70% lysine (50% moderate lysine restriction) and 0.35% lysine (75% severe lysine restriction) were fed from the age of 52 to 77 days for 25 days in male Sprague-Dawley rats. The 75% severe lysine restriction increased (p < 0.05) food intake, but retarded (p < 0.05) growth, increased (p < 0.05) liver and muscle lipid contents and abdominal fat accumulation, increased (p < 0.05) blood urea nitrogen levels and mRNA levels of the serine-synthesizing 3-phosphoglycerate dehydrogenase gene, but decreased (p < 0.05) urea cycle arginase gene mRNA levels. In contrast, the 50% lysine restriction did not significantly (p > 0.05) affect body growth and lipid and nitrogen metabolism. Our results demonstrate that severe 75% lysine restriction has detrimental effects on body growth and deregulate lipid and nitrogen metabolism.


Subject(s)
Body Composition/drug effects , Gene Expression Regulation/drug effects , Liver/enzymology , Lysine/deficiency , Nitrogen/metabolism , Amino Acids/blood , Animals , Blood Urea Nitrogen , Liver/metabolism , Male , RNA, Messenger/genetics , RNA, Messenger/metabolism , Rats , Rats, Sprague-Dawley
12.
J Nanosci Nanotechnol ; 13(5): 3554-8, 2013 May.
Article in English | MEDLINE | ID: mdl-23858901

ABSTRACT

The effect of thermal dissipation by adding graphene nano-platelets to two different commercially available thermal dissipation coatings (ceramic coating and powder coating) was studied. Steady state temperatures of each points of LED modules was monitored in a closed system, with an integral photo detection sphere where there is no external air flow. Having eliminated the contributions of thermal conduction and air flow convection, the module with a conventional heat dissipation coatings showed 8-16% enhancement of thermal dissipation compared to that of non-coated LED module. The addition of graphene is shown to have about 3% additional enhancement. By analyzing thermal resistance of each component of the LED module, the improved thermal conductivity of the graphene added coatings contributes to the enhancement of slight improvement with heat dissipation.


Subject(s)
Graphite/chemistry , Lighting/instrumentation , Nanostructures/chemistry , Nanostructures/ultrastructure , Semiconductors , Energy Transfer , Equipment Design , Equipment Failure Analysis , Hot Temperature , Particle Size , Thermal Conductivity
13.
Anim Genet ; 44(6): 627-35, 2013 Dec.
Article in English | MEDLINE | ID: mdl-23742632

ABSTRACT

Intramuscular fat (IMF) is an important trait that influences beef quality. In two studies, we examined the possible involvement of the Wnt/ß-catenin signaling pathway in IMF deposition in Korean cattle. In study 1, using a group of bulls and steers, we found that castration, a non-genetic factor, decreased (P < 0.01) the expression of both the WNT10B and CTNNB1 genes, whereas it increased the expression of the Wnt antagonist secreted frizzled-related proteins 4 (SFRP4, P < 0.001) and the adipogenic CCAAT/enhancer binding protein (C/EPB), alpha (CEBPA, P < 0.001) and peroxisome proliferator-activated receptor gamma (PPARG, P < 0.05) genes in longissimus dorsi muscle (LM) tissue. The WNT10B and CTNNB1 mRNA levels showed strong (P < 0.001) negative correlations (r = -0.68 and r = -0.73 respectively) with the IMF content, whereas the SFRP4, CEBPA and PPARG mRNA levels showed strong (P < 0.01) positive correlations (r = 0.70, 0.70 and 0.64 respectively) with the IMF content. Large variation still exists in the IMF content of steers, implying that genetic factors affect IMF deposition. Using a different group of steers, a correlation analysis in study 2 also showed that the expression of the WNT10B and CTNNB1 genes, and SFRP4 and adipogenic genes was negatively and positively associated with the IMF content respectively. Our findings suggest that downregulation of the Wnt/ß-catenin signaling pathway genes, but upregulation of Wnt antagonist SFRP4 and adipogenic gene expression following castration, contributes to increased IMF deposition in the LM. Our results demonstrate that both non-genetic factors (castration) and genetic variation within the steer group affect the gene expression pattern of the Wnt/ß-catenin signaling pathway.


Subject(s)
Body Composition/genetics , Cattle/genetics , Gene Expression Regulation/genetics , Lipids/analysis , Meat/standards , Muscle, Skeletal/metabolism , Wnt Signaling Pathway/genetics , Adipogenesis/genetics , Animals , Blotting, Western , Cattle/metabolism , DNA Primers/genetics , Real-Time Polymerase Chain Reaction/veterinary , Republic of Korea , beta Catenin/genetics , beta Catenin/metabolism
14.
Br J Cancer ; 109(2): 452-61, 2013 Jul 23.
Article in English | MEDLINE | ID: mdl-23807165

ABSTRACT

BACKGROUND: MicroRNAs are noncoding regulatory RNAs strongly implicated in carcinogenesis, cell survival, and chemosensitivity. Here, microRNAs associated with chemoresistance in ovarian carcinoma, the most lethal of gynaecological malignancies, were identified and their functional effects in chemoresistant ovarian cancer cells were assessed. METHODS: MicroRNA expression in paclitaxel (PTX)-resistant SKpac sublines was compared with that of the PTX-sensitive, parental SKOV3 ovarian cancer cell line using microarray and qRT-PCR. The function of differentially expressed microRNAs in chemoresistant ovarian cancer was further evaluated by apoptosis, cell proliferation, and migration assays. RESULTS: Upregulation of miR-106a and downregulation of miR-591 were associated with PTX resistance in ovarian cancer cells and human tumour samples. Transfection with anti-miR-106a or pre-miR-591 resensitized PTX-resistant SKpac cells to PTX by enhancing apoptosis (23 and 42% increase), and inhibited their cell migration (43 and 56% decrease) and proliferation (64 and 65% decrease). Furthermore, ZEB1 was identified as a novel target gene of miR-591, and BCL10 and caspase-7 were target genes of miR-106a, as identified by immunoblotting and luciferase assay. CONCLUSION: MiR-106a and miR-591 have important roles in conferring PTX resistance to ovarian cancer cells. Modulation of these microRNAs resensitizes PTX-resistant cancer cells by targeting BCL10, caspase-7, and ZEB1.


Subject(s)
Cystadenocarcinoma, Serous/drug therapy , Cystadenocarcinoma, Serous/genetics , Drug Resistance, Neoplasm/genetics , MicroRNAs/genetics , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/genetics , Paclitaxel/therapeutic use , Antineoplastic Agents, Phytogenic/therapeutic use , Cell Line, Tumor , Cluster Analysis , Cystadenocarcinoma, Serous/mortality , Female , Gene Expression Regulation, Neoplastic/physiology , Humans , MicroRNAs/physiology , Microarray Analysis , Ovarian Neoplasms/mortality , Survival Analysis , Transcriptome
15.
Infection ; 41(1): 111-9, 2013 Feb.
Article in English | MEDLINE | ID: mdl-23065454

ABSTRACT

PURPOSE: Persistent Staphylococcus aureus bacteremia (SAB) has been observed in patients with eradicated foci, but there are few studies of the risk factors and clinical outcomes of persistent bacteremia. This study determined the risk factors for persistent methicillin-resistant S. aureus (MRSA) bacteremia in patients without retained eradicable foci, including genotypic characteristics. METHODS: All adult SAB patients were investigated between 2008 and 2010. Persistent bacteremia was defined as bacteremia lasting >7 days after treatment and patients were monitored prospectively. The study included patients without retained eradicable foci, e.g., removed prosthetic devices and intravenous catheters removed after diagnosis, and those without metastatic infections. RESULTS: Persistent bacteremia occurred in 36 % (31/87) SAB patients with eradicated foci. There were no significant differences in successful defervescence (2.0 vs. 2.0 days, P = 0.55) and total length of hospital stay after bacteremia in the persistent bacteremia group and resolved bacteremia group (P = 0.32). The difference in MRSA bacteremia-related 30-day mortality with persistent bacteremia and resolved bacteremia was not significant (P = 0.12). However, agr dysfunction was higher in persistent bacteremia patients (94 %) than those with resolved bacteremia (75 %, P = 0.03). Multivariate analysis using a logistic regression model found that only agr dysfunction [odds ratio (OR) 4.83, 95 % confidence interval (CI) 1.02-22.89, P = 0.04] was an independent risk factor for persistent bacteremia. CONCLUSIONS: This study suggests that persistent bacteremia with eradicated foci might not adversely affect the outcome for MRSA bacteremia patients. agr dysfunction in S. aureus was significantly associated with persistent bacteremia.


Subject(s)
Bacteremia/microbiology , Bacterial Proteins/metabolism , Methicillin-Resistant Staphylococcus aureus/metabolism , Staphylococcal Infections/microbiology , Trans-Activators/metabolism , Aged , Anti-Bacterial Agents/therapeutic use , Bacteremia/drug therapy , Bacteremia/epidemiology , Female , Genotype , Humans , Male , Methicillin-Resistant Staphylococcus aureus/genetics , Middle Aged , Risk Factors , Staphylococcal Infections/drug therapy , Staphylococcal Infections/epidemiology , Treatment Outcome
16.
Diabetologia ; 56(2): 412-22, 2013 Feb.
Article in English | MEDLINE | ID: mdl-23150180

ABSTRACT

AIMS/HYPOTHESIS: Fenofibrate is a drug used to treat hyperlipidaemia that works by inhibiting hepatic triacylglycerol synthesis. Sterol regulatory element binding protein-1c (SREBP-1c) is a major regulator of the expression of genes involved in hepatic triacylglycerol synthesis. In addition, endoplasmic reticulum (ER)-bound transcription factor families are involved in the control of various metabolic pathways. Here, we show a novel function for an ER-bound transcription factor, cAMP response element binding protein H (CREBH), in fenofibrate-mediated inhibition of hepatic lipogenesis. METHODS: The effects of fenofibrate and adenovirus-mediated Crebh (also known as Creb313) overexpression (Ad-Crebh) on hepatic SREBP-1c production and lipogenesis in vitro and in vivo were investigated. We also examined whether downregulation of endogenous hepatic Crebh by small interfering (si)RNA restores the fenofibrate effect on hepatic lipogenesis and SREBP-1c production. Finally, we examined the mechanism by which CREBH inhibits hepatic SREBP-1c production. RESULTS: Fasting and fenofibrate treatment induced CREBH production and decreased SREBP-1c levels. Indeed, Ad-Crebh inhibited insulin- and liver X receptor agonist TO901317-induced Srebp-1c (also known as Srebf1) mRNA expression in cultured hepatocytes. Moreover, increased production of CREBH in the liver of mice following tail-vein injection of Ad-Crebh inhibited high-fat diet-induced hepatic steatosis through inhibition of Srebp-1c expression. The inhibition of endogenous Crebh expression by siRNA restored fenofibrate-induced suppression of Srebp-1c expression and hepatic lipid accumulation both in vitro and in vivo. CONCLUSIONS/INTERPRETATION: These results show that fenofibrate decreases hepatic lipid synthesis through induction of CREBH. This study suggests CREBH as a novel negative regulator of SREBP-1c production and hepatic lipogenesis.


Subject(s)
Cyclic AMP Response Element-Binding Protein/metabolism , Fenofibrate/pharmacology , Lipogenesis/drug effects , Liver/drug effects , Liver/metabolism , Animals , Cell Line , Cell Line, Tumor , Fatty Liver/metabolism , Hep G2 Cells , Humans , Mice , Rats , Sterol Regulatory Element Binding Protein 1/metabolism
17.
Asian-Australas J Anim Sci ; 26(7): 1047-53, 2013 Jul.
Article in English | MEDLINE | ID: mdl-25049884

ABSTRACT

Five hundred and forty crossbred (Korean native black pig×Landrace) F2 were selected at a commercial pig farm and then divided into six different coat color groups: (A: Black, B: White, C: Red, D: White spot in black, E: Black spot in white, F: Black spot in red). Birth weight, 21st d weight, 140th d weight and carcass weight varied among the different coat color groups. D group (white spot in black coat) showed a significantly higher body weight at each weigh (birth weight, 140th d weight and carcass weight) than did the other groups, whereas the C group (red coat color) showed a significantly lower body weight at finishing stage (140th d weight and carcass weight) compared to other groups. Meat quality characteristics, shear force, cooking loss and meat color were not significantly different among the different coat color groups, whereas drip loss was significantly higher in F than in other groups. Most blood characteristics were not significantly different among the different groups, except for the red blood cells.

18.
Eur J Clin Microbiol Infect Dis ; 31(12): 3309-16, 2012 Dec.
Article in English | MEDLINE | ID: mdl-22833245

ABSTRACT

Patients with liver cirrhosis (LC) have impaired immunity and thus are predisposed to infections. Few studies have attempted to evaluate Staphylococcus aureus bacteremia (SAB) in LC patients. Therefore, this study prospectively evaluated the clinical characteristics and outcomes of 642 episodes of SAB from August 1, 2008 to September 31, 2010. Of 642 patients with SAB, 109 (17.0 %) were classified as LC patients whereas the remaining 533 (83.0 %) were classified as non-LC patients. The 30-day mortality rate of LC patients was significantly higher than that of patients with other diseases (32 % vs. 22 %, respectively; P = 0.047). The 30-day mortality rates of patients with MSSA bacteremia and MRSA bacteremia were not significantly different among LC patients (35.1 % with MSSA vs. 26.9 % with MRSA; P = 0.41). A univariate analysis of the 30-day mortality rate of LC patients with SAB for survivors and non-survivors showed that rapidly fatal or ultimately fatal according to the criteria of McCabe and Jackson (OR 5.0; 95 % CI 1.60-15.65), septic shock at initial presentation (OR 3.5; 95 % CI 1.18-10.39) and Child-Pugh class C (OR 2.8; 95 % CI 1.20-6.59) were associated with increased mortality. In contrast, the removal of the eradicable focus was associated with decreased mortality (OR 0.14; 95 % CI 0.04-0.52). Disease severity and liver dysfunction may be useful for predicting the prognosis of SAB in LC patients.


Subject(s)
Bacteremia/mortality , Bacteremia/pathology , Liver Cirrhosis/complications , Staphylococcal Infections/mortality , Staphylococcal Infections/pathology , Adolescent , Adult , Aged , Aged, 80 and over , Cohort Studies , Female , Humans , Liver Function Tests , Male , Middle Aged , Prognosis , Prospective Studies , Severity of Illness Index , Staphylococcus aureus/isolation & purification , Survival Analysis , Young Adult
19.
Eur J Clin Microbiol Infect Dis ; 31(3): 303-10, 2012 Mar.
Article in English | MEDLINE | ID: mdl-21667269

ABSTRACT

Because Enterococcus avium is rarely isolated from blood cultures, little is known about the clinical features and outcomes of bacteremia caused by this organism, formerly called "group Q streptococcus". We retrospectively evaluated the clinical features and outcomes of patients with clinically significant bacteremia caused by E. avium presenting at a tertiary-care hospital in Korea between February 1997 and February 2009. We identified 53 patients over the 12-year period; of these, 27 (50.9%) had biliary and 13 (24.5%) had intra-abdominal E. avium infections. Thirty-six (67.9%) of the episodes were polymicrobial. Thirty-three (62.3%) episodes were nosocomial bloodstream infections and resistance to vancomycin was not observed. The crude mortality rate was 24.5% (13/53), and the E. avium bacteremia-related mortality rate was 11.3% (6/53). Multivariate analysis showed that underlying rapidly fatal or ultimately fatal disease (adjusted odds ratio [AOR], 6.92; 95% confidence interval [CI], 1.56-30.65; P = 0.011) and inadequate antimicrobial therapy (AOR, 7.29; CI, 1.27-41.93; P = 0.026) were independent risk factors for mortality. In summary, bacteremia due to E. avium was commonly of biliary or intraabdominal origin and was often associated with polymicrobial bacteremia. The crude mortality rate was considerable. Severe underlying conditions and inadequate antimicrobial therapy were significant and independent risk factors for crude patient mortality.


Subject(s)
Bacteremia/microbiology , Enterococcus/drug effects , Enterococcus/pathogenicity , Gram-Positive Bacterial Infections/drug therapy , Gram-Positive Bacterial Infections/mortality , Adolescent , Adult , Aged , Aged, 80 and over , Anti-Infective Agents/therapeutic use , Child , Child, Preschool , Female , Gram-Positive Bacterial Infections/blood , Humans , Male , Microbial Sensitivity Tests , Middle Aged , Retrospective Studies , Risk Factors , Treatment Outcome , Vancomycin/therapeutic use , Young Adult
20.
Hum Pathol ; 43(2): 254-60, 2012 Feb.
Article in English | MEDLINE | ID: mdl-21820147

ABSTRACT

Studies detailing differences in positive surgical margin among open retropubic radical prostatectomy, laparoscopic radical prostatectomy, and robotic-assisted laparoscopic radical prostatectomy are lacking. A retrospective review of all prostatectomies with positive surgical margin performed at our center in 2007 disclosed 99 cases, 6 (5%) of which were reinterpreted cases as having negative margins. Ninety-three cases were, therefore, included, corresponding to 37 retropubic radical prostatectomies, 19 laparoscopic radical prostatectomies, and 37 robotic-assisted laparoscopic radical prostatectomies. The relationship of positive surgical margin characteristics to clinicopathologic parameters and biochemical recurrence was assessed. The most commonly found positive surgical margin site was the apex/distal third in all groups (62% retropubic prostatectomies, 79% laparoscopic prostatectomies, 60% robotic-assisted prostatectomies). Total linear length of positive surgical margin sites was significantly correlated with preoperative prostate-specific antigen, preoperative prostate-specific antigen density, pT stage, and tumor volume (P ≤ .001). We found no significant differences among the 3 groups with respect to total linear length, number of foci, laterality, or location of positive surgical margin. The rate of biochemical recurrence was also comparable in the 3 groups. On univariate analyses, biochemical recurrence was significantly associated with preoperative prostate-specific antigen values, preoperative prostate-specific antigen density, Gleason score, number of positive surgical margins, and total linear length of positive surgical margin (P ≤ .02). Only preoperative prostate-specific antigen density and number of positive surgical margin foci were statistically significant (P ≤ .03) independent predictors of biochemical recurrence. We found no significant difference in positive surgical margin characteristics or biochemical recurrence among the 3 radical prostatectomy modalities. Preoperative prostate-specific antigen density and number of positive surgical margin foci were the only independent predictors of biochemical recurrence.


Subject(s)
Adenocarcinoma/pathology , Laparoscopy/methods , Prostatectomy/methods , Prostatic Neoplasms/pathology , Robotics , Adenocarcinoma/blood , Adenocarcinoma/surgery , Adult , Aged , Humans , Male , Middle Aged , Neoplasm Recurrence, Local , Neoplasm Staging , Organ Size , Prostate-Specific Antigen/blood , Prostatectomy/instrumentation , Prostatic Neoplasms/blood , Prostatic Neoplasms/surgery , Retrospective Studies
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