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91.
92.
Koichi Kimura Kensuke Kudo Tomoharu Yoshizumi Takeshi Kurihara Shohei Yoshiya Yohei Mano Kazuki Takeishi Shinji Itoh Noboru Harada Toru Ikegami Tetsuo Ikeda 《World Journal of Clinical Cases》2019,7(10):1149-1154
BACKGROUND In patients with large stones in the common bile duct(CBD),advanced treatment modalities are generally needed.Here,we present an interesting case of a huge CBD stone treated with electrohydraulic lithotripsy(EHL)by the percutaneous approach and rendezvous endoscopic retrograde cholangiography(ERC)using a nasal endoscope.CASE SUMMARY A 91-year-old woman underwent ERC for a symptomatic large CBD stone with a diameter of 50 mm.She was referred to our institution after the failure of lithotomy by ERC,and after undergoing percutaneous transhepatic biliary drainage.We attempted to fragment the stone by transhepatic cholangioscopy using EHL.However,the stones were too large and partly soft clay-like for lithotripsy.Next,we attempted lithotomy with ERC and cholangioscopy by the rendezvous technique using a nasal endoscope and achieved complete lithotomy.No complication was observed at the end of this procedure.CONCLUSION Cholangioscopy by rendezvous technique using a nasal endoscope is a feasible and safe endoscopic method for removing huge CBD stones. 相似文献
93.
Ishibashi M Hiasa K Zhao Q Inoue S Ohtani K Kitamoto S Tsuchihashi M Sugaya T Charo IF Kura S Tsuzuki T Ishibashi T Takeshita A Egashira K 《Circulation research》2004,94(9):1203-1210
Activated monocytes are present in the arterial walls of hypertensive patients and animals. Monocyte chemoattractant protein-1 (MCP-1), which controls monocyte function through its receptor (CCR2), is implicated in hypertensive inflammatory changes in the arterial wall. The role of CCR2 expression on monocytes in hypertension-induced vascular remodeling, however, has not been addressed. We hypothesized that CCR2 on monocytes is critical in hypertension-induced vascular inflammation and remodeling. Hypertension was induced by infusion of angiotensin II (Ang II) into wild-type mice, CCR2-deficient (CCR2-/-) mice, and bone marrow-transferred mice with a leukocyte-selective CCR2 deficiency (BMT-CCR2-/-). In wild-type mice, Ang II increased CCR2 intensity in circulating monocytes, which was prevented by an Ang II type-1 (AT1) receptor blocker or blunted in AT1 receptor-deficient mice. Enhanced CCR2 intensity on monocytes was observed in hypertensive patients and rats, and was reduced by treatment with the Ang II receptor blocker, supporting the clinical relevance of the observation in mice. In CCR2-/- and BMT-CCR2-/- mice, Ang II-induced vascular inflammation and vascular remodeling (aortic wall thickening and fibrosis) were blunted as compared with control mice. In contrast, Ang II-induced left ventricular hypertrophy developed in CCR2-/- and BMT-CCR2-/- mice. The present study suggests that CCR2 expression in monocytes has a critical role in vascular inflammation and remodeling in Ang II-induced hypertension, and possibly in other forms of hypertension. 相似文献
94.
95.
Atsushi Hamabe Masamitsu Konno Nobuhiro Tanuma Hiroshi Shima Kenta Tsunekuni Koichi Kawamoto Naohiro Nishida Jun Koseki Koshi Mimori Noriko Gotoh Hirofumi Yamamoto Yuichiro Doki Masaki Mori Hideshi Ishii 《Proceedings of the National Academy of Sciences of the United States of America》2014,111(43):15526-15531
96.
97.
98.
Junya Kuroda Yuji Shimura Kensuke Ohta Hirokazu Tanaka Hirohiko Shibayama Satoru Kosugi Shinichi Fuchida Masayuki Kobayashi Hitomi Kaneko Nobuhiko Uoshima Kazuyoshi Ishii Shosaku Nomura Masafumi Taniwaki Akifumi Takaori-Kondo Chihiro Shimazaki Mitsuru Tsudo Masayuki Hino Itaru Matsumura Yuzuru Kanakura 《International journal of hematology》2014,99(4):441-449
We retrospectively investigated clinical outcomes and prognostic factors of 131 patients with transplant-ineligible newly diagnosed multiple myeloma (NDMM) who received melphalan and prednisolone (MP) as first-line therapy from 2006 to 2013. Eighty-one patients received salvage therapies incorporating bortezomib, lenalidomide, and/or thalidomide. The overall response rate to MP was 54.2 %, including 9.2 % of better than very good partial response. With a median follow-up period of 30.2 months, median overall survival (OS) and median time to next treatment (TNT) were 54.4 and 19.0 months, respectively. Univariate analysis revealed that performance status and serum calcium level significantly associated with both OS and TNT, and multivariate analysis revealed that the higher serum calcium level had a significantly unfavorable impact on OS and TNT. Importantly, staging informed by the international staging system (ISS) was not predictive for OS or TNT in the analyzed cohort. Our study revealed that, in the context of first-line MP therapy for NDMM, the salvage therapy incorporating novel agents produced a survival period of >30 months after the initiation of second-line therapy, suggesting that the predictive value of ISS for OS and TNT may be limited in the era of novel agents. 相似文献
99.
In this study, in situ catalytically generated allylic indium from 1,3 dienes and InCl2H was developed for use in the allylation of ketones. This protocol resulted in the unprecedented establishment of a successive combining of quaternary C–C bonds, which could then be applied to many types of ketones. Other branched 1,3 dienes and vinyl cyclopropanes, could also be coupled with ketones in a reaction where CuH would not be applicable.In this study, in situ catalytically generated allylic indium from 1,3 dienes and InCl2H was developed for use in the allylation of ketones.Homoallylic alcohols are useful building blocks in the synthesis of bioactive natural compounds and pharmaceuticals. For these syntheses, the preparation of tertiary compounds has remained challenging regardless of whether or not they are given asymmetrically.1 The allylation of ketones with allylic reagents is a typical method for the preparation of these compounds (Scheme 1a).2 This method, however, cannot avoid wasteful steps such as the transmetalation between Grignard reagents and B, Si or Sn sources and the reductive generation between allylic halides and low-valent metals. Although this method can be applied to highly stereocontrolled reactions, the wasteful steps are cumbersome and more practical reaction methods are required.Open in a separate windowScheme 1Synthesis of homoallylic alcohols from allylation reagents with ketones.For this process, 1,3-dienes are an important industrial feedstock that is produced on a massive scale via either the cracking of ethylenes or the transformation of biomass. Easily available dienes have recently replaced the conventional allylation of aldehydes with the aid of transition metal catalysts (Scheme 1b).3 After the first application using a Ti catalyst by Gendre and Moïse,4 Krische has expanded the field with the introduction of Ru-catalyzed stereocontrolled reactions.5 Other transition metals such as Ni,6 Ir,7 and Rh8 have contributed to improvements in coupling. A recent adoption of ketones as viable substrates was achieved by Liu and Buchwald via proficient Cu–H chemistry.9 The scope of possible substrates could be expanded even further,10 however, particularly with the use of 1,3-dienes and ketones that possess a variety of functional groups.Our group has explored the hydrostannylation11 or indation12 of unsaturated bonds in the preparation of reactive organostannanes or indiums that could be applied to further transformations, although stoichiometric amounts of Sn or In sources must be added to the reaction systems. Recently, a transition metal-free reductive coupling of 1,3-dienes,13 or their derivatives such as vinyl cyclopropanes,14 with aldehydes catalyzed by Bu2SnXH has been developed, but the method would not allow the use of ketones due to the low reactivity of the reaction intermediate, allylic stannanes (Scheme 1c). On the other hand, our group has already developed a process for the hydroindation of 1,3-dienes with a stoichiometric amount of InX2H to give allylic indiums followed by the allylation of ketones.12b,12d Herein, we report the catalytic coupling of 1,3-dienes or vinyl cyclopropanes with ketones through the generation of allylic indiums via the hydroindation of 1,3-dienes with a catalytic amount of InX2H (Scheme 1c).We initiated the optimization of the reaction conditions by combining 1,3-butadiene (1a) and acetophenone (2a) in a sealed test tube (Table 1). The gaseous diene 1a was liquefied and weighed before addition to the reaction. Based on our previous reports, InCl2OMe generated from InCl3/NaOMe and a silane were chosen as indium and hydride sources, respectively.13 The desired product 3aa was obtained in a 92% yield as a mixture of the diastereomers (entry 1). The yield was lowered either when no MeOH was used or when the reaction time was cut by half (entries 2 and 3). A screening of the silanes showed that MePhSiH2 was the optimal hydride source (entries 4–7). We found that the reaction was finished in 3 h when the reaction temperature was raised to 60 °C (entry 8). Replacing the solvent with MeCN, Et2O or toluene did not improve the reaction yield (entries 9–11). It was necessary to add NaOMe to the reaction system for a facile generation of InCl2H (entry 12).16 It was important to add InCl3 to the reaction (entry 13). A radical scavenger, TEMPO, suppressed the progress of the reaction, which implied that this reaction contains a radical process (entry 14). The reaction yield was decreased when the lower amount of the catalyst was employed (entry 15).Optimization of the reaction conditionsa
Open in a separate windowaThe yields were determined by 1H NMR.bStereochemistry, see: ref. 15.cdr could not be determined because of complex of the reaction mixture.With the optimal reaction conditions in hand (Table 1, entry 8), the scope of the ketones was investigated (Table 2). Electron-deficient substitution on the phenyl ring had a small effect on the reaction yield, but an electron-rich substitution decreased it appreciably (entries 2–6). The efficiency was also attenuated by steric hindrance around the C O moiety of propiophenone (2g) and butyrophenone (2h) (entries 7 and 8). α-Cyano and -bromo acetophenone 2i and 2j, respectively, reacted sufficiently (entries 9 and 10). The tolerance to reduction of the C–Br bond by InX2H under reductive conditions is a characteristic of coupling (entries 3 and 10).17 On the other hand, α-methoxy one was unsatisfactory as a reactant probably due to chelation between the OMe and C O groups with the catalyst that would have promoted a reduction in the ketone 2k (entry 11). β-Keto ester 2l was a good partner even though a similar chelation involving two C O groups could have happened (entry 12). Both acyclic and cyclic aliphatic ketones were allylated (entries 13–14). Other aromatic rings such as naphthalenes were introduced into the products 3ao and 3ap (entries 15 and 16).Scope of ketonesa
Open in a separate windowaThe yields were determined by 1H NMR.bReaction time was 24 h.Reductive coupling was then applied to other dienes (Scheme 2). In the case of isoprene (1b), two different products, 3ba and 3ba′, were formed even though the reaction was very slow (eqn (1)). The regioselectivity derived from the different structures of the allylic indiums. To our delight, diene 1c made it possible to establish contiguous quaternary C–C bonds with ketones 2a–2c (eqn (2)). To date, construction of contiguous quaternary C–C bonds with a catalyst remains a challenging task in organic synthesis,18 and the task has never been realized by the same type of reductive coupling that is catalyzed by transition metal catalysts.Open in a separate windowScheme 2Application of substituted 1,3-butadienes to the coupling.Our proposal of the reaction mechanism is described in Scheme 3. Initially, prepared InCl2(OMe) is reduced by MePhSiH2 to give HInCl2. The indium radical is formed in the presence of tiny amounts of O2 and adds to diene 1a.17 The stable allylic radical A extracts hydrogen from InCl2H to afford allylic indium B, which regenerates the indium radical. Following the allylation of ketone 2, the generated indium alkoxide 3′ is protonated by CH3OH to give the product 3 and InCl2(OMe). The reaction mechanism was investigated using a deuterated silane, Ph2SiD2 (Scheme 4). We found that the product 3aa-CH2D was afforded without any other deuterated compound. The product 3aa-CH2D is formed from δ-deuterated intermediate B-d1 as shown in Scheme 4. Further investigation on the reaction mechanism is ongoing in our laboratory.Open in a separate windowScheme 3A plausible catalytic cycle.Open in a separate windowScheme 4Deuterated experiments of allylation of ketone 2a.Finally, vinyl cyclopropane 4, a diene derivative, was tested for reductive coupling with ketones.19 The desired product 5a was produced in the presence of a radical initiator, V-70L, even though diastereoselectivity was not achieved (Scheme 5, eqn (1)). This could have been caused by low E/Z selectivity of the allylic indiums. The seminal work developed by Buchwald that was related to a Cu–H catalyzed reaction did not allow the use of vinyl cyclopropane as a reactant because their method has no process for a radical opening of the cyclopropane ring (Scheme 5, eqn (2)).9 Our method expands the scope of the dienes by allowing use of their derivatives.Open in a separate windowScheme 5Coupling of vinyl cyclopropanes with ketones.In summary, we developed a process whereby the reductive coupling of 1,3-dienes with various ketones could be sufficiently catalyzed by HInCl2. This approach allowed the introduction of functional groups into homoallylic alcohols, which generated sequential Ctert–Ctert bonds with expansion to vinyl cyclopropane 4. Application to an asymmetric version of the coupling and improvement of the diastereoselectivity are underway. 相似文献
| Entry | Silane | Solvent | Conditions | Yield (%)3aa (syn : anti)b |
|---|---|---|---|---|
| 1 | MePhSiH2 | THF | 25 °C, 48 h | 92 (80 : 20) |
| 2 | 25 °C, 48 h w/o MeOH | 42 (88 : 12) | ||
| 3 | 25 °C, 24 h w/o MeOH | 54 (76 : 24) | ||
| 4 | Et3SiH | THF | 25 °C, 24 h | 12c |
| 5 | Ph3SiH | THF | 25 °C, 24 h | 0 |
| 6 | Ph2SiH2 | THF | 25 °C, 24 h | 32 (83 : 17) |
| 7 | PhSiH3 | THF | 25 °C, 24 h | 54 (83 : 17) |
| 8 | MePhSiH2 | THF | 60 °C, 3 h | 92 (80 : 20) |
| 9 | MeCN | 38 (80 : 20) | ||
| 10 | Et2O | 71 (76 : 42) | ||
| 11 | Toluene | 9c | ||
| 12 | THF | w/o NaOMe | Trace | |
| 13 | w/o InCl3 | 0 | ||
| 14 | With TEMPO (0.2 mmol) | 0 | ||
| 15 | With InCl2OMe (0.1 mmol) | 51 (78 : 22) |
| Entry | R1 | R2 | Ketone | Product | Yield (%) (dr) |
|---|---|---|---|---|---|
| 1 | C6H5 | Me | 2a | 3aa | 92 (80 : 20) |
| 2 | p-ClC6H4 | 2b | 3ab | 83 (79 : 21) | |
| 3 | p-BrC6H4 | 2c | 3ac | 88 (80 : 20) | |
| 4 | p-CNC6H4 | 2d | 3ad | 79 (79 : 21) | |
| 5 | p-MeC6H4 | 2e | 3ae | 53 (75 : 25) | |
| 6 | p-OMeC6H4 | 2f | 3af | 58 (75 : 25) | |
| 7 | C6H5 | Et | 2g | 3ag | 69 (84 : 16) |
| 8 | n Pr | 2h | 3ah | 66 (84 : 16) | |
| 9 | CH2CN | 2i | 3ai | 75 (82 : 18) | |
| 10 | CH2Br | 2j | 3aj | 74 (84 : 16) | |
| 11 | CH2OMe | 2k | 3ak | 22 (80 : 20) | |
| 12 | CH2CO2Et | 2l | 3al | 59 (80 : 20) | |
| 13b | PhCH2CH2–(CH2)5– | Me | 2m | 3am | 73 (57 : 43) |
| 14 | 2n | 3an | 75 | ||
| 15 | 1-Np | Me | 2o | 3ao | 77 (75 : 25) |
| 16 | 2-Np | Me | 2p | 3ap | 80 (76 : 24) |
100.
Yasunori Sawayama Masafumi Tatsukawa Kensuke Kikuchi Shinji Maeda Hachiro Ohnishi Norihiro Furusyo Jun Hayashi 《Journal of infection and chemotherapy》2007,13(2):92-98
To investigate the effect of levofloxacin on carotid atherosclerosis, patients with hypercholesterolemia whose carotid atherosclerosis
was not improved by probucol therapy (500 mg/day) for 24 months were enrolled. All patients were seropositive for anti C. pneumoniae IgA and/or IgG. Carotid atherosclerosis was evaluated by ultrasonic measurement of the maximum intima-media thickness (Max-IMT).
All subjects were prescribed three courses of levofloxacin (each course, 400 mg/day for 2 weeks, followed by 14 days off drug
treatment). At 12 months after combined therapy with probucol and levofloxacin, Max-IMT was significantly decreased compared
with the value before treatment (P < 0.01). These results suggest that the combination therapy was effective for improving carotid atherosclerosis in C. pneumoniae-seropositive patients. 相似文献