Immobilization of simulated reducing agent at the surface of SiO2 fillers in dental composite resins

To reduce the leachability of reducing agents from composite resins, immobilization of a simulated reducing agent at the surface of SiO2 fillers was examined. SiO2 plates were immersed in 2% 3-aminopropyltriethoxy silane/ethanol solution, and then immersed in dimethyl sulfoxide with 0.25 wt% 4-dimethyl amino benzoic acid (DMABA), 2.0 wt% 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride, and 0.5 wt% N-hydroxysuccinimide. Wide-scan spectrum of X-ray photoelectron spectroscopy did not detect carbon contamination. However, narrow scan detected an O=C-N peak at 399.8 eV, suggesting that DMABA could be immobilized on silane-coupled SiO2 plates. Further, surface plasmon resonance analysis indicated the adsorption of MMA at the surface of reducing agent-immobilized plate.     

Expression of Tumor-rejection Antigens in Gynecologic Cancers

We recently reported the four tumor-rejection antigens (SART1₂₅₉ SART2, SART3, and ART4) that possess tumor epitopes capable of inducing HLA-A2402-restricted cytotoxic T lymphocytes (CTLs) in cancer patients. This study investigated the expression of these tumor antigens in gynecologic cancers, including 33 ovarian cancers, 38 cervical cancers, and 40 endometrial cancers. SART1₂₅₉ antigen was detected in 56%, 35%, and 30% of ovarian, cervical and endometrial cancers, while SART2 antigen was detected in 46%, 66%, and 30% of these cancers, respectively. Both SART3 and ART4 antigens were detectable in the majority of these gynecologic cancers tested. In contrast, none of these antigens was detectable in any of the normal ovarian and uterine tissues tested. Peripheral blood mononuclear cells (PBMCs) of HLA-A24⁺ patients with gynecologic cancers were found to produce significant levels of interferon-γ in response to HLA-A24⁺ SART3⁺ gynecologic cancer cells after having been stimulated three times in vitro with either SART3_109–118 or SART3_315–323 peptide. These PBMCs lysed HLA-A24⁺ SART3⁺ gynecologic cancer cells, but not HLA-A24^- SART3⁺ gynecologic cancer cells or HLA-A24⁺ normal cells. Therefore, these four antigens and their peptides, including SART3 peptides, would be appropriate molecules for use in specific immunotherapy of HLA-A24⁺ gynecologic cancer patients.     

New guiding catheter for transrad PTCA

A new guiding catheter for PTCA is described. In our department, 302 patients (405 lesions) underwent transradial coronary angioplasty using the 6 Fr Kimny guiding catheter since January 1996. The total engagement rate using the Kimny guiding catheter was 91.3% (370/405). The engagement rate after the modified Kimny guiding catheter was introduced in May 1996 increased to 96.0% (243/253). The stent delivery success rate was 98.4%. We had two dislodged stents. PTCA for both left and right coronary arteries in a single procedure with the Kimny guiding catheter was performed via the radial artery in 27 patients. In 24 of these patients (89%) we engaged both coronaries successfully. In the remaining 3 patients we switched to another catheter. Except for 4 patients with non-Q-wave myocardial infarction, no major cardiac complications were encountered. No major entry site-related complications were seen, and no patient required vascular surgery or blood transfusions. In one patient the Kimny guiding catheter tip caused a minor dissection of the LMT, but no ischemic event occurred as a result. In conclusion, the Kimny device is a useful PTCA guiding catheter for routine angioplasty and stenting. Cathet. Cardiovasc. Diagn. 43:344–351, 1998. © 1998 Wiley-Liss, Inc.     

Expression of the SART‐1 tumor rejection antigen in breast cancer

We investigated in breast cancers the expression of the SART‐1 gene encoding tumor rejection antigens. SART‐1 mRNA was expressed in all of the samples tested. The SART‐1₈₀₀ antigen was detectable in 20 of 50 (40%) breast cancer tissues and all breast cancer cell lines tested, but not in normal breast tissues. The SART‐1₈₀₀⁺ breast cancer cells transfected with HLA‐A2601 or HLA‐A2402 cDNA were recognized by the HLA‐A26‐restricted and SART‐1‐specific cytotoxic T lymphocytes (CTLs) or the HLA‐A24‐restricted and SART‐1‐specific CTLs, respectively. Among the 20 SART‐1₈₀₀⁺ tumors, 9 or 8 tumors expressed estrogen receptor or progesterone receptor, respectively. Therefore, the patients with HLA‐A26 or ‐A24 haplotype might be appropriate candidates for specific immunotherapy with the SART‐1 peptides independently or in combination with hormone therapy. Int. J. Cancer 80:64–67, 1999. © 1999 Wiley‐Liss, Inc.     

异氟烷复合caspase抑制剂减轻局部脑缺血损伤

背景 :近来研究提示异氟烷的神经保护作用不是持续的。由细胞凋亡介导的神经元的延迟性死亡可导致梗死面积的逐渐增加。这些资料提示异氟醚可能不能抑制延迟性神经元死亡。除了异氟烷外 ,caspase抑制剂的神经细胞凋亡预防作用可以提供神经保护作用。本研究的开展是决定在非特异性的caspase抑制剂z VAD fmk存在下异氟烷的神经保护作用是否更持久。方法 :Wister大鼠分为清醒 zVAD组 ,清醒 载体组 ,异氟烷 -zVAD组或异氟烷 -载体组 ,每组 16只。使用细丝线阻塞大脑中动脉造成后局部脑缺血6 0min。清醒组 ,异氟烷在阻塞大脑中动脉后停止给…     

Axonal protection by 17β-estradiol through thioredoxin-1 in tumor necrosis factor-induced optic neuropathy

Axonal degeneration often leads to the death of neuronal cell bodies. Previous studies demonstrated the substantial protective role of 17β-estradiol (E2) in several types of neuron. However, most studies examined cell body protection, and the role of 17β-E2 in axonal degeneration of retinal ganglion cells (RGC) remains unclear. In this study, we showed the presence of thioredoxin-1 (Trx1) in the optic nerve axons and found that the levels of Trx1 protein were significantly decreased in isolated RGC and the optic nerve after intravitreal injection of TNF, which was shown previously to induce optic nerve degeneration and subsequent loss of RGC. These changes were concomitant with disorganization of the microtubules with neurofilament accumulation, which were blocked by 17β-E2 implantation. 17β-E2 treatment also totally abolished TNF-induced decreases in Trx1 protein levels in isolated RGC and the optic nerve. The induction of Trx1 by 17β-E2 in the optic nerve was significantly inhibited by simultaneous injection of Trx1 small interfering RNA (siRNA) with TNF. Up-regulation of Trx1 by 17β-E2 in RGC-5 cells was prevented by Trx1 siRNA treatment. 17β-E2 significantly prevented TNF-induced axonal loss, and this axonal-protective effect was inhibited by intravitreal injection of Trx1 siRNA. This finding was also supported by the quantification of microtubules and neurofilaments. These results suggest that a Trx1 decrease in RGC bodies and their axons may be associated with TNF-induced optic nerve axonal degeneration. Axonal protection by 17β-E2 may be related to its regulatory effect on Trx1 induction.     

Personalized peptide vaccination in patients with refractory non-small cell lung cancer

Since the prognosis of non-small cell lung cancer (NSCLC) remains poor, the development of novel therapeutic approaches, including cancer vaccines, is highly desirable. In the current study, we conducted a phase II study of personalized peptide vaccination (PPV), in which a maximum of 4 peptides were selected based on pre-existing humoral immune responses and administered subcutaneously (weekly for 6 consecutive weeks and bi-weekly thereafter) in refractory NSCLC patients. Forty-one refractory NSCLC patients (4 stage IIIb, 22 stage IV and 15 recurrent), who had failed to respond to chemotherapy and/or targeted therapy (median number of regimens, 3; median duration, 10 months), were enrolled. Median overall survival (OS) was 304 days with a one-year survival rate of 42% in the enrolled patients. The main toxicity of PPV was skin reactions at the injection sites, but no serious adverse events were observed. In order to identify potential biomarkers for predicting OS, pre-vaccination and post-vaccination clinical findings and laboratory data were retrospectively assessed and evaluated by multivariate Cox regression analysis. Among the pre-vaccination factors examined, high C-reactive protein (CRP) level was a significant predictor of unfavorable OS [hazard ratio (HR)=10.115, 95% confidence interval (CI)=2.447-41.806, P=0.001]. Among the post-vaccination factors, high CRP level and low frequency of CD3?CD26? cells were significant predictors of unfavorable OS (HR=23.127, 95% CI=2.919-183.233, P=0.003; HR=0.952, 95% CI=0.917-0.989, P=0.012). Taken together, our results suggest the feasibility of PPV for the treatment of refractory NSCLC. Evaluation of the identified factors before or at an early stage of vaccination could be potentially useful for selecting NSCLC patients who would likely have better prognosis following PPV.     

SAR Exploration Guided by LE and Fsp3: Discovery of a Selective and Orally Efficacious RORγ Inhibitor

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Mechanism of pathogenesis of imiquimod‐induced skin inflammation in the mouse: A role for interferon‐alpha in dendritic cell activation by imiquimod

Topical application of imiquimod (IMQ), a Toll‐like receptor (TLR)7 ligand, can induce and exacerbate psoriasis, a chronic inflammatory skin disorder. In a mouse model of IMQ‐induced psoriasis‐like skin inflammation, T‐helper (Th)17 cells and interleukin (IL)‐17/IL‐22‐producing γδ‐T cells have been shown to play a pivotal role. However, the mechanisms of induction of the Th17 pathway and development of psoriasis‐like skin inflammation by IMQ treatment remain unclear. In this study, we investigated pathogenic mechanisms of IMQ‐induced psoriasis‐like skin inflammation in mice. We first confirmed that, together with an increase in IL‐17 and IL‐22 production, application of IMQ to mouse skin induced the expression of cytokines required for activation of the Th17 pathway, and pro‐inflammatory mediators involved in the pathology of psoriasis. Analysis of Tlr7^?/? mice demonstrated that most of the in vivo effects of IMQ were mediated via TLR7. In an in vitro study using plasmacytoid dendritic cells (DCs), IMQ induced production of interferon (IFN)‐α, IL‐23, IL‐6 and tumor necrosis factor (TNF)‐α. Furthermore, when we analyzed in vitro‐generated bone marrow‐derived DCs with features similar to TNF‐α and inducible nitric oxide synthase (iNOS)‐producing DCs, IL‐23, IL‐6, IL‐1β, TNF‐α and iNOS/NO production was weakly induced by IMQ alone and further enhanced after co‐stimulation with IMQ and IFN‐α. These in vitro effects of IMQ were also mediated via TLR7 and the synergistic effect of IMQ, and IFN‐α was suggested to be caused by upregulation of TLR7 expression by IFN‐α. These results demonstrate part of the mechanism by which the Th17 pathway and psoriasis‐like skin inflammation are induced by IMQ and IFN‐α in a mouse model.