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1.
Toshihiro Yoshitake Akira Takeda Kensaku Ohki Yuko Inoue Takanori Yamawaki Saori Otsuka Minekatsu Akimoto Mitsuru Nemoto Yasuhito Shimakura Akio Sato 《The Journal of dermatology》2015,42(7):735-738
Finasteride is standard medical treatment for androgenetic alopecia; however, no large studies with 5 years or more of follow up have been performed in Japan. The authors followed Japanese men with androgenetic alopecia treated with finasteride for 5 years to evaluate long‐term treatment efficacy. Of 903 men treated with finasteride (1 mg/day), 801 patients were evaluated over 5 years by modified global photographic assessment. Although the proportion of improvement was high (99.4%), modified global photographic assessment scores after 5 years of treatment were lower in patients with more advanced disease as measured by the modified Norwood–Hamilton scale. After separating patients into “sufficient” and “insufficient” efficacy groups according to the modified global photographic assessment score after 5 years (scores ≥6 and <6, respectively), multivariate analysis showed that independent risk factors of insufficient efficacy were age at start of treatment of 40 years or more (P = 0.021) and classification on the modified Norwood–Hamilton scale (P < 0.001), whereas presence of stress at start of treatment was a negative predictor (P = 0.025). In conclusion, continuous finasteride treatment for 5 years improved androgenetic alopecia with sustained effect among Japanese. Younger age and less advanced disease at start of treatment were the key predictors of higher finasteride efficacy. 相似文献
2.
A case of bullous pemphigoid associated with psoriasis vulgaris showing Hailey–Hailey disease‐like histopathological changes in regenerated epidermis without genomic mutation in ATP2C1 or ATP2A2 gene 下载免费PDF全文
3.
Daisuke Ishibashi Takeshi Ishikawa Satoshi Mizuta Hiroya Tange Takehiro Nakagaki Tsuyoshi Hamada Noriyuki Nishida 《Neurotherapeutics》2020,17(4):1836
The accumulation of abnormal prion protein (PrPSc) produced by the structure conversion of PrP (PrPC) in the brain induces prion disease. Although the conversion process of the protein is still not fully elucidated, it has been known that the intramolecular chemical bridging in the most fragile pocket of PrP, known as the “hot spot,” stabilizes the structure of PrPC and inhibits the conversion process. Using our original structure-based drug discovery algorithm, we identified the low molecular weight compounds that predicted binding to the hot spot. NPR-130 and NPR-162 strongly bound to recombinant PrP in vitro, and fragment molecular orbital (FMO) analysis indicated that the high affinity of those candidates to the PrP is largely dependent on nonpolar interactions, such as van der Waals interactions. Those NPRs showed not only significant reduction of the PrPSc levels but also remarkable decrease of the number of aggresomes in persistently prion-infected cells. Intriguingly, treatment with those candidate compounds significantly prolonged the survival period of prion-infected mice and suppressed prion disease-specific pathological damage, such as vacuole degeneration, PrPSc accumulation, microgliosis, and astrogliosis in the brain, suggesting their possible clinical use. Our results indicate that in silico drug discovery using NUDE/DEGIMA may be widely useful to identify candidate compounds that effectively stabilize the protein.Electronic supplementary materialThe online version of this article (10.1007/s13311-020-00903-9) contains supplementary material, which is available to authorized users. 相似文献
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Sadahiro Hijikata Igen Hongo Shu-ichi Nakayama Tetsuo Yamaguchi Yoshiyuki Sekikawa Toshihiro Nozato Takashi Ashikaga 《The Canadian journal of cardiology》2019,35(1):104.e9-104.e11
Syphilis is a sexually transmitted disease caused by Treponema pallidum. Syphilitic aortitis might coexist in a dysfunctional aortic valve, but the etiology remains unclear, because microbiological diagnosis is difficult. A 62-year-old man with low-grade fever was diagnosed with aortitis and infective endocarditis, due to Treponema pallidum infection, using polymerase chain reaction analysis. This case suggests that syphilis might cause infective endocarditis. 相似文献
6.
Hiroki Koshimichi Yoshiyuki Tsuda Toru Ishibashi Toshihiro Wajima 《Journal of pharmaceutical sciences》2019,108(5):1896-1904
Baloxavir marboxil, a prodrug that is metabolized to baloxavir acid, suppresses viral replication by inhibiting cap-dependent endonuclease. Our aim is to characterize its pharmacokinetics and exposure-response relationships. Population pharmacokinetic analysis of the baloxavir acid was performed using 8310 plasma concentration data points from 1109 subjects. Exposure-response analyses were performed regarding the time to alleviation of symptoms and the reduction in the influenza virus titer. A 2-compartment model with first-order absorption and lag time well described the plasma concentration data for baloxavir acid, and body weight and race were found to be the most important factors influencing the clearance and distribution volume. A dose regimen based on the body weight (40 mg for patients weighing <80 kg and 80 mg for patients weighing ≥80 kg) could provide sufficient exposures for expecting efficacy irrespective of body weight or race; however, the exposures were dependent on the body weight and race. Exposure-response analyses suggested that the reduction in the influenza virus titer was greater in any exposure-based groups in baloxavir marboxil treatment than in the oseltamivir phosphate treatment and placebo groups. In conclusion, the population pharmacokinetic model and exposure-response relationships would be useful for understanding the pharmacokinetic and pharmacodynamic characteristics of baloxavir acid. 相似文献
7.
Yasushi Sawayama Hidehiro Itonaga Takuya Fukushima Nobuaki Nakano Hiroshi Fujiwara Atae Utsunomiya Takahiro Fukuda Toshihiro Miyamoto Tetsuya Eto Kaname Miyashita Hirohisa Nakamae Masao Ogata Atsushi Yamanoha Yasuhiko Miyazaki Junya Kanda Yoshiko Atsuta Koji Kato ATL Working Group of the Japan Society for Hematopoietic Cell Transplantation 《American journal of hematology》2019,94(5):E143-E146
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9.
Takaharu Negoro Kanami Orihara Tomoko Irahara Hiroshi Nishiyama Kanae Hagiwara Risa Nishida Hiroki Takagi Kazue Satoh Yoshiki Yamamoto Shunichi Shimizu Tamio Hagiwara Masakazu Ishii Toshihiro Tanioka Yasuko Nakano Ken Takeda Isao Yoshimura Yoji Iikura Takashi Tobe 《Pediatric allergy and immunology》2006,17(8):583-590
Although many single nucleotide polymorphism (SNP) studies have reported an association of atopy, allergic diseases and total serum immunoglobulin E (IgE) levels, almost all of these studies sought risk factors for the onset of these allergic diseases. Furthermore, many studies have analyzed a single gene and hardly any have analyzed environmental factors. In these analyses, the results could be masked and the effects of other genes and environmental factors may be decreased. Here, we described the correlation between four genes [interleukin (IL)-4 (C-590T), IL-4 receptor (A1652G), FCER1B (G6842A) and STAT6 (G2964A)] in connection with IgE production; the role of IL-10 (C-627A) as a regulatory cytokine of allergy; and the severity of food allergy (FA) and atopic eczema (AE) in 220 Japanese allergic children. In addition to these SNPs, environmental factors, i.e., patient's attitude, indoor environment, and so on, were also investigated in this study. Our study was retrospective, and the correlation was analyzed by our defined clinical scores divided into three terms: worst symptoms, recent symptoms and general amelioration at the most recent examination during the disease course. Our results indicated that IL-10 AA, the genotype with lower IL-10 production, is associated with higher IgE levels in the serum (p < 0.0001, estimate; 0.912). Marginal liver abnormalities were observed in the subject group with both FA and AE (p < 0.1191, estimate; 0.1490). Our defined clinical scores enabled evaluation of various aspects of disease severity. Based on the scores, while no single SNP selected in this study determined severity, the combination of the SNP with laboratory data and environmental factors appeared to determine severity. 相似文献
10.
We studied two patients with nonfamilial olivopontocerebellar atrophy with skeletal myoclonus. Palatal or skeletal myoclonus is probably not a coincidental finding but another manifestation of the underlying disease. In both cases, the myoclonus was suppressed by administration of trihexyphenidyl, indicating a cholinergic disorder. 相似文献