Reversible Photo‐Mechanical Switching Behavior of Azobenzene‐Containing Semi‐Interpenetrating Network under UV and Visible Light Irradiation

Summary: Light‐induced reversible changes in elasticity of semi‐interpenetrating network (semi‐IPN) films bearing azobenzene moieties were achieved under both ultraviolet (UV) and visible light irradiation. The semi‐IPN film was prepared by a cationic copolymerization of azobenzene‐containing vinyl ethers in a linear polycarbonate (PC) film as a matrix. When the irradiation was switched on and off, the semi‐IPN film showed rapid reversible deformation with the same behavior occurring over a range of wavelengths, including both the UV and visible regions. The observed reversible deformation of the film was attributed to the decrease in the film's elasticity, which was assumed to be caused by the frequent trans‐cis cycling isomerization of azobenzene moieties taking place during the UV and visible light irradiation. This cycling makes it difficult for the azobenzene groups to aggregate, thus hindering their ability to function as pseudo‐crosslinking points.

     

Relation of aortic arch complex plaques to risk of cerebral infarction in patients with aortic stenosis

Aortic stenosis (AS) and systemic atherosclerosis have been shown to be closely related. We evaluated the prevalence of aortic arch plaques and their possible association with the risk of cerebral infarction in patients with severe AS. Transesophageal echocardiography was performed in 116 patients with severe AS (55 men, mean age 71 ± 7 years, mean aortic valve area 0.68 ± 0.15 cm(2)) who were scheduled for aortic valve replacement. The presence, thickness, and morphology of the aortic arch plaques were evaluated using transesophageal echocardiography. Cerebral infarcts (chronic cerebral infarction and cerebral infarction after cardiac catheterization and aortic valve replacement) were assessed in all patients. Compared to age- and gender-matched control subjects, the patients with severe AS had a significantly greater prevalence of aortic arch plaques (74% vs 41%; p <0.0001) and complex arch plaques such as large plaques (≥4 mm), ulcerated plaques, or mobile plaques (30% vs 10%; p = 0.004). Multivariate logistic analyses showed that the presence of complex arch plaques was independently associated with cerebral infarction in patients with AS after adjusting for traditional atherosclerotic risk factors and coronary artery disease (odds ratio 8.46, 95% confidence interval 2.38 to 30.12; p = 0.001). In conclusion, the results from the present study showed that there is a greater prevalence of aortic arch plaques in patients with AS and that the presence of complex plaques is independently associated with cerebral infarction in these patients. Therefore, the identification of complex arch plaques using transesophageal echocardiography is important for risk stratification of cerebrovascular events in patients with severe AS.     

Dexamethasone induces sodium-dependant vitamin C transporter in a mouse osteoblastic cell line MC3T3-E1

The regulation of intracellular ascorbic acid (AsA) levels may be under the control of an AsA-specific membrane transporter. The present study investigates AsA uptake and expression of Na-dependent vitamin C transporter (SVCT) mRNA in the mouse osteoblastic cell line, MC3T3-E1. Among eight compounds tested, dexamethasone (Dex) all-trans retinoic acid, transforming growth factor beta, prostaglandin E2 and transferrin significantly and respectively) stimulated the update of AsA into MC3T3-E1 cells. Among these five, Dex was the most active, inducing mSVCT2 mRNA and the uptake of AsA in a time- and concentration-dependant manner. Dex did not induce mSVCT1 mRNA. These results suggest that the Dex-induced stimulation of AsA incorporation into osteoblastic cells is mediated by the induction of mSVCT2. Since Dex reduced alkaline phosphatase activity in MC3T3-E1 cells in our culture conditions, Dex-induced stimulation of AsA incorporation might not be the result of differentiation. Hormone-regulated changes of SVCT expression may have an important role in cell functions.     

Impact of chronic kidney disease on oncological outcomes in patients with high-risk non-muscle-invasive bladder cancer who underwent adjuvant bacillus Calmette-Guérin therapy

ObjectivesTo investigate the impact of chronic kidney disease (CKD) on oncological outcomes in patients with high-risk non-muscle invasive bladder cancer (NMIBC) who underwent adjuvant induction bacillus Calmette-Guérin (BCG) therapy after transurethral resection of bladder tumor (TURBT).Materials and MethodsWe conducted a multi-institutional retrospective study assessing 209 patients with high-risk NMIBC who underwent TURBT and subsequent adjuvant induction BCG therapy from December 1998 to April 2019. Patients were divided into 2 groups: those with preoperative estimated glomerular filtration rate (eGFR) ≥ 60 ml/min/1.73 m² (non-CKD group), and those with eGFR < 60 ml/min/1.73 m² (CKD group). Primary endpoints were intravesical recurrence-free survival (RFS) and muscle-invasive bladder cancer (MIBC)-free survival. Background-adjusted multivariate analyses with the inverse probability of treatment weighting (IPTW) method using the propensity score were performed to evaluate the impact of CKD on intravesical RFS, MIBC-free survival, metastasis-free survival, cancer-specific survival, and overall survival. Moreover, multivariable analyses were performed to assess the impact of CKD on intravesical recurrence and MIBC progression, adjusting for the competing risk of death using the Fine-Gray competing risk regression model.ResultsMedian age and follow-up period after TURBT were 72 years and 45 months, respectively. Of 209 patients, 71 (34%) were diagnosed with CKD before TURBT. Background-adjusted multivariate analyses with the IPTW method indicated that CKD was significantly associated with shorter intravesical RFS, MIBC-free survival, metastasis-free survival, cancer-specific survival, and overall survival. In the Fine-Gray competing risk regression model, CKD showed significantly higher probabilities of intravesical recurrence and MIBC progression, with an adjusted subdistribution hazard ratio of 1.886 (95% confidence interval 1.069–3.330, P = 0.028) and 3.740 (95% confidence interval 1.060–13.20, P = 0.040), respectively.ConclusionsCKD presents a risk factor of poor oncological outcomes in patients with high-risk NMIBC who underwent adjuvant induction BCG therapy after TURBT.     

Inhibition of phorbol ester-induced phenotypic differentiation of HL-60 cells by 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine, a protein kinase inhibitor

To identify the possible role of calcium ions in cell differentiation, we studied the extracellular Ca2+ requirement and the effect of Ca2+/phospholipid-dependent protein kinase (protein kinase C) inhibitor on proliferation and differentiation of human promyelocytic leukemic HL-60 cells. HL-60 cells grew equally well in 0.1 and 1.0 mM Ca2+ media. The addition of 12-O-tetradecanoyl-phorbol-13-acetate (TPA), 1,25-dihydroxyvitamin D3, and all-trans-beta-retinoic acid inhibited the cell growth and induced mature macrophage and granulocyte phenotypes in 1.0 mM Ca2+ medium. 1,25-Dihydroxyvitamin D3 and all-trans-beta-retinoic acid induced HL-60 differentiation to the same degree in 0.1 mM Ca2+ and 1.0 mM Ca2+ media. However, TPA failed to induce HL-60 differentiation or to inhibit proliferation in a 0.1 mM Ca2+ medium. The decrease of extracellular Ca2+ from 1.0 to 0.1 mM caused a significant drop in the intracellular Ca2+ level in undifferentiated and TPA-treated HL-60 cells, although no rapid change in cytosolic Ca2+ was detected in response to TPA addition. 1-(5-Isoquinolinylsulfonyl)-2-methylpiperazine (H-7), a protein kinase C inhibitor, inhibited proliferation of HL-60 cells in a dose-dependent manner. In contrast, H-7 selectively restored the proliferation of TPA-treated HL-60 cells and inhibited TPA-induced phenotypic differentiation. However, the same concentrations of 1-(5-isoquinolinylsulfonyl)-2,3-dimethylpiperazin and N-[2-(methylamino)ethyl]-5-isoquinolinesulfonamide, analogues of H-7 that inhibit protein kinase C more weakly, had no effect on the proliferation or differentiation induction. H-7 also suppressed 1,25-dihydroxyvitamin D3- and all-trans-beta-retinoic acid-induced phenotypic changes of HL-60 cells but did not eliminate the growth inhibition by these inducers. These results demonstrate the Ca2+ requirement and the protein kinase C involvement in phorbol ester-induced phenotypic differentiation of HL-60 cells.     

Association of eNOS Glu298Asp polymorphism with end-stage renal disease

Nitric oxide (NO) derived from endothelial cells is profoundly related to the maintenance of physiological vascular tone. Impairment of endothelial NO generation brought about by gene polymorphism is considered the major deterioration factor for progressive renal disease, including diabetic nephropathy. The present study aimed to elucidate the Glu298Asp polymorphism of endothelial NO synthase (eNOS) in patients with end-stage renal disease (ESRD) and its role as a predisposing factor for cardiovascular complications. Glu298Asp in exon 7 of the eNOS gene was determined by polymerase chain reaction, followed by restriction fragment length polymorphism analysis, in ESRD patients (n=185) and compared with that of unrelated healthy individuals (n=304). The occurrence of 298Asp was significantly higher in the ESRD group (P=0.0020; odds ratio [OR] 1.65; 95% confidential interval [CI]: 1.21 to 2.25). In this group, 72 patients had type 2 diabetes mellitus (DM). Although 298Asp did not reach a significant level in the non-DM ESRD subgroup, the occurrence of 298Asp was significantly higher in DM-derived ESRD patients (P=0.0010; OR 2.02; 95% CI: 1.37 to 3.07). The functional effect of the Glu298Asp was examined using Chinese hamster ovary (CHO) cells stably overexpressing either 1917G or 1917T. NO-selective electrode measurements and fluorometric nitrite assay revealed a statistically significant difference in NO production or nitrite accumulation between CHO 1917G and 1917T (P<0.01). These data indicated that Glu298Asp is the predisposing factor in ESRD, especially DM-derived ESRD. The functional difference in NO generation depending on eNOS with either glutamate or aspartate at position 298 was also confirmed in vitro.     

The Effectiveness of Video Technology As an Adjunct to Teach and Evaluate Epidural Anesthesia Performance Skills

Background: Although video review has been used in teaching, it has not been reported for use as an adjunct to teaching anesthesiology residents. The purpose of the prospective, randomized, blinded study was to determine whether teaching with video review improves epidural anesthesia skills of anesthesiology residents.

Methods: Twenty-two second-year (CA-2) anesthesiology residents beginning their first obstetric anesthesia rotation were assigned to video or nonvideo groups. All residents were filmed daily as they placed epidural analgesia. Residents assigned to the video group reviewed their tapes twice a week with an attending anesthesiologist, whereas residents assigned to the nonvideo group never saw their films. Four experienced attending anesthesiologists independently judged videotapes taken on days 1, 15, and 30 and scored the residents for "overall" skill (range of summed overall grades, 0-40), as well as on 13 predetermined criteria.

Results: As determined by kappa coefficients, interrater reliability was high among the judges (k = 0.7-0.8). Residents in the video group improved to a greater degree than residents in the nonvideo group. On day 1, the median overall grades for the video and nonvideo groups were 21 and 12, respectively. By day 15, the corresponding grades had increased to 32 and 24, respectively (P < 0.01). However, overall median grades continued to improve between days 15 and 30 in the video group only (P < 0.01).     

Four Rous sarcoma virus mutants which affect transformed cell morphology exhibit altered src gene products

Four Rous sarcoma virus Schmidt Ruppin A (RSV SR-A) morph^f mutants (ST529, WO101, W0201, and WO401), independently isolated in the presence of different mutagens, cause an elongated, or fusiform, transformed cell morphology in chicken embryo fibroblasts at 37°. The src gene products isolated from cells transformed by these mutants exhibited an apparent molecular weight (M_r) of approximately 54,000 to 55,000 on SDS-polyacrylamide gels, in contrast to the approximately 59,000 to 60,000 M_r pp60^src species isolated from wt SR-A-transformed cells, using the same extraction conditions. This difference was observed both in extraction buffers containing SDS, sodium deoxycholate, and NP-40, as well as in buffers not containing SDS and sodium deoxycholate. Partial protease digestion experiments indicated that src gene products of all four mutants were lacking peptides present in the N-terminal half of wt pp60P^src The mutant src species isolated from cells transformed at 37° exhibited kinase activity; in the case of the temperature-sensitive mutant ST529, this activity displayed a pronounced in vitro temperature sensitivity. These results strongly suggest that a common, or similar, structural alteration in “pp60^src” species of the mutants is intimately related to, and perhaps the cause of, the morph^f phenotype exhibited by the cells they transform.