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吡酮酸类抗菌药物的研究Ⅷ.1-对氟苯基-6-氟-1,4-二氢-4-氧-7-(1-哌嗪)噌啉-3-羧酸及其类似物的合成和构效关系 总被引:1,自引:0,他引:1
为探讨构效关系,合成了1-对氟苯基-6-氟-1,4-二氢-4-氧-7-(1-哌嗪)噌啉-3-羧酸及其喹啉、萘啶、吡啶[2,3-C]哒嗪环系类似物16个。测定了对大肠杆菌的MIC。用Hückel分子轨道理论(HMO)方法计算了四个母体环上电子密度。结果表明:环中氮的位置对药效团——3位羧基和4位羰基氧原子上电子密度的影响较大而影响其抗菌活性。喹啉、萘啶两环系的3位羧基和4位羰基氧原子上的电子密度较高,其体外抗菌活性较高;而噌啉及吡啶[2,3-C]哒嗪两环系的电子密度较低,其体外抗菌活性较低甚至消失。 相似文献
3.
Jang AS Choi IS Lee S Nam HS Kweon SS Son MH Lee JH Park SW Kim DJ Uh ST Kim YH Park CS 《Journal of Korean medical science》2004,19(2):214-217
Passive smoking is a major cause of respiratory morbidity, and is associated with increased bronchial responsiveness in children. To evaluate the effect of smoking by a parent on asthma symptoms, atopy, and airway hyperresponsiveness (AHR), we conducted a cross-sectional survey of 503 schoolchildren that involved questionnaires, spirometry, allergy testing, and a bronchial challenge test. If the PC20 methacholine was less than 16 mg/mL, the subject was considered to have AHR. The prevalence of a parent who smoked was 68.7%. The prevalence of AHR was 45.0%. The sensitization rate to common inhalant allergens was 32.6%. Nasal symptoms such as rhinorrhea, sneezing, nasal itching, and nasal obstruction were present in 42.7%. Asthma symptoms such as cough and wheezing were present in 55.4%. The asthma symptoms were significantly more prevalent in children who had a parent who smoked than in those whose parents did not. The nasal symptoms, atopy, and AHR did not differ according to whether a parent smoked. In a multiple logistic regression model, the asthma symptoms and atopy were independently associated with AHR, when adjusted for confounding variables. Passive smoking contributed to asthma symptoms in schoolchildren and was not an independent risk factor of airway hyperresponsiveness in an epidemiological survey. 相似文献
4.
Kim YT Jung MK Cho CM Tak WY Kweon YO Kim SK Choi YH Chung JM 《Journal of Korean medical science》2002,17(6):772-777
Transjugular intrahepatic portosystemic shunt (TIPSS) is a promising method of treatment for gastric or esophageal variceal bleeding. This study was performed to determine the prognostic factors contributing to the survival of patients after TIPSS for gastric or esophageal variceal bleeding. One hundred and fifty-five patients who underwent TIPSS between September 1991 and March 2001 were followed up by clinical examination, upper gastrointestinal endoscopy, and Duplex sonography. The mean portohepatic pressure gradient prior to TIPSS was 20.5+/-9.93 mmHg and dropped to 10.7+/-6.62 mmHg after TIPSS (p<0.001). The cumulative survival rate was 75.1% at 6 months, 66.6% at 1 yr, 58.4% at 2 yr, and 38.1% at 5 yr. Survival after TIPSS was inversely related to the Child-Pugh classification (p<0.05). The rebleeding rate was 18.3% at 6 months, 21.0% at 1 yr, 32.8% at 2 yr, and 53.1% at 5 yr. The causes of deaths were hepatic failure (53.5%), recurrent variceal bleeding (11.6%), pneumonia (4.6%), sepsis (3.5%), hepatic encephalopathy (2.3%), and unknown (17.4%). Multivariate analysis (Cox proportional hazard model) revealed that the Child-Pugh classification and age were statistically significant independent prognostic factors. In conclusion, TIPSS is an effective method of treatment for variceal bleeding in cases where other treatment modalities including endoscopic therapy are unsuccessful and the most important prognostic factors are preprocedural hepatic reserve (Child-Pugh class) and age. 相似文献
5.
Thomas V. Harwood Esthefani G. Zuniga HoJun Kweon Douglas D. Risser 《Proceedings of the National Academy of Sciences of the United States of America》2021,118(12)
Motility is ubiquitous in prokaryotic organisms including the photosynthetic cyanobacteria where surface motility powered by type 4 pili (T4P) is common and facilitates phototaxis to seek out favorable light environments. In cyanobacteria, chemotaxis-like systems are known to regulate motility and phototaxis. The characterized phototaxis systems rely on methyl-accepting chemotaxis proteins containing bilin-binding GAF domains capable of directly sensing light, and the mechanism by which they regulate the T4P is largely undefined. In this study we demonstrate that cyanobacteria possess a second, GAF-independent, means of sensing light to regulate motility and provide insight into how a chemotaxis-like system regulates the T4P motors. A combination of genetic, cytological, and protein–protein interaction analyses, along with experiments using the proton ionophore carbonyl cyanide m-chlorophenyl hydrazine, indicate that the Hmp chemotaxis-like system of the model filamentous cyanobacterium Nostoc punctiforme is capable of sensing light indirectly, possibly via alterations in proton motive force, and modulates direct interaction between the cyanobacterial taxis protein HmpF, and Hfq, PilT1, and PilT2 to regulate the T4P motors. Given that the Hmp system is widely conserved in cyanobacteria, and the finding from this study that orthologs of HmpF and T4P proteins from the distantly related model unicellular cyanobacterium Synechocystis sp. strain PCC6803 interact in a similar manner to their N. punctiforme counterparts, it is likely that this represents a ubiquitous means of regulating motility in response to light in cyanobacteria.Motility is ubiquitous in prokaryotic organisms, including both swimming motility in aqueous environments and twitching or gliding motility on solid surfaces, and enables these organisms to optimize their position in response to various environmental factors. Among the photosynthetic cyanobacteria, surface motility is widespread and facilitates phototaxis to seek out favorable light environments (1, 2), and, for multicellular filamentous cyanobacteria, plays a key role in dispersal as well as the establishment of nitrogen-fixing symbioses with eukaryotes (3) and the formation of supracellular structures (3–5).Current understanding of cyanobacterial surface motility at the molecular level has been informed primarily by studies of two model organisms, the unicellular strain Synechocystis sp. strain PCC6803 (herein Synechocystis) and the filamentous strain Nostoc punctiforme ATCC29133/, where motility is exhibited only by differentiated filaments termed “hormogonia.” Motility in both organisms is powered by a type IV pilus (T4P) system where the ATPases PilB and PilT drive the extension and subsequent retraction, respectively, of pili which adhere to the substrate and pull the cells forward (for review, see ref. PCC731026). In Synechocystis, the T4P motors are distributed throughout the entire cell, allowing a 360 ° range of motion (7), whereas in N. punctiforme they are confined to rings at the cell poles (8), resulting in movement only along the long axis of the filament. Comparative genomics implies that this mechanism of motility is widely conserved among cyanobacteria (9).Both Synechocystis and N. punctiforme employ chemotaxis-like systems to regulate motility. One of these systems, the Hmp chemotaxis-like system of N. punctiforme (3, 10), and its orthologous counterpart, the Pil chemotaxis-like system of Synechocystis (11), includes homologs to the canonical Escherichia coli chemotaxis complex (for review, see ref. 12), including the histidine kinase CheA, the adaptor protein CheW, the response regulator CheY, and the methyl-accepting chemotaxis protein MCP. These systems are essential for motility in their respective organisms and appear to regulate the T4P motors, although there are distinct differences in the phenotypes for inactivation of the components from each. In Synechocystis, null mutations either enhance or reduce the level of surface piliation (11), whereas in N. punctiforme they disrupt the coordinated polarity, but not the overall level of piliation, and affect various other aspects of hormogonium development (3, 10). In N. punctiforme, the subcellular localization of this system has been determined and has been found arrayed in static, bipolar rings similar to the T4P motors (3). However, the signals that are perceived by the MCPs and the precise mechanism by which these systems modulate T4P activity is currently undefined.Recently, an additional component of the Hmp system, HmpF, was characterized (9). HmpF is a predicted coiled-coil protein and is ubiquitous to, but confined within, the cyanobacterial lineage (9). It is essential for accumulation of surface pili and exhibits dynamic, unipolar localization to the leading poles of most cells in hormogonium filaments (9). Based on these findings, a model has been proposed where the localization of HmpF is regulated by the other components of the Hmp system, and in turn, the unipolar accumulation of HmpF leads to the activation of the T4P motors on one side of the cell to facilitate directional movement.A second chemotaxis-like system in each organism, the Ptx system of N. punctiforme (13) and the Pix system of Synechocystis (14, 15), is essential for positive phototaxis. These systems contain MCPs with cyanobacteriochrome sensory domains capable of perceiving light (for review, see ref. 16). Disruption of the Pix system results in negative phototaxis under light conditions that normally produce a positive phototactic response (14). Several other proteins containing cyanobacteriochromes, and one containing a BLUF domain, also modulate phototaxis in Synechocystis (for review, see ref. 6). In N. punctiforme, disruption of the Ptx system abolishes the phototactic response completely, resulting in uniform movement in all directions regardless of the light conditions (13), and there are currently no other proteins reported to modulate phototaxis. More recently, a motile, wild isolate of the model unicellular cyanobacterium Synechococcus elongatus sp. PCC7942 was shown to possess a chemotaxis-like system that modulates phototaxis in a manner similar to that of the N. punctiforme Ptx system (17). How these systems influence T4P activity to facilitate phototaxis is also currently unknown.There is also a substantial body of literature on motility and phototaxis in cyanobacteria, primarily based on observational studies of various filamentous strains, that predates the development of genetically tractable model organisms (for review, see ref. 18). These reports suggested that the photosystems may serve a sensory role in modulating phototaxis and that proton motive force (PMF) powers motility (19, 20), a finding that is inconsistent with the theory that cyanobacteria possess a common T4P-based gliding motor driven by ATP hydrolysis. In this study, we help reconcile this historical data with more recent molecular studies by providing evidence that the Hmp chemotaxis-like system senses light, possibly indirectly through alterations in PMF, and in turn modulates the interaction of HmpF with the T4P base to activate the motors. 相似文献
6.
7.
Ji Ho Choi Seung Hoon Lee Jae Hoon Cho Sung Wan Kim Kyu Sup Cho Soo Kweon Koo Tae-Bin Won Jeong-Whun Kim Hyo Yeol Kim Yoo Suk Kim Yoo-Sam Chung Chae-Seo Rhee 《Clinical and experimental otorhinolaryngology》2015,8(4):370-375
Objectives
To evaluate the effect of obstructive sleep apnea (OSA) surgery on long-term (5-year) subjective outcomes, including sleep disordered breathing (SDB) symptoms and other complications, in patients with OSA.Methods
We enrolled patients who underwent diagnostic polysomnography for OSA between January 2006 and December 2006 in ten hospitals. Patients either were treated for OSA or were not treated for OSA. All patients completed a brief telephone survey regarding their SDB signs and symptoms (e.g., snoring, apnea, nocturnal arousals, and daytime sleepiness), positive airway pressure (PAP) compliance, and any adverse effects of either the surgery or PAP. A positive subjective outcome for either surgery or no treatment was taken to be the alleviation of apnea, defined as a ≥50% increase in score. A positive subjective outcome (compliance) for PAP was defined as a PAP usage of ≥4 hours per night and ≥5 days per week.Results
A total of 229 patients were included in this study. Patients were divided into three groups: a surgery group (n=87), a PAP group (n=68), and a control (untreated) group (n=74). The surgery group exhibited significant improvement in all SDB symptoms compared with the control group. The long-term subjective outcomes of the surgery (52.9%) and PAP (54.4%) groups were significantly better than those of the control group (25.0%). The subjective outcome of the surgery group was not significantly different from that of the PAP group. The overall surgical complication rate was 23.0% (20 of 87) in the surgery group, and 55.0% (22 of 40) of all patients with PAP experienced adverse effects.Conclusion
The extent of SDB symptoms was consistently improved in patients with OSA at 5 years postsurgery. Information about the potential long-term subjective outcomes should be provided to patients when considering surgery. 相似文献8.
Joo Youn Shin Jae Bum Lee Kyoung Yul Seo Eung Kweon Kim Tae-im Kim 《Yonsei medical journal》2013,54(5):1259-1265
Purpose
To compare preoperative and postoperative ocular biometry in patients with iris-fixated phakic intraocular lens (pIOLs): Artisan and Artiflex.Materials and Methods
This study included 40 eyes with Artisan and 36 eyes with Artiflex pIOL implants. Anterior chamber depth (ACD) and axial length (AL) were measured by applanation ultrasonography (A-scan) and partial coherence interferometry (IOLMaster) preoperatively and 3 months after pIOL implantation.Results
ACD measurements after Artisan or Artiflex pIOL implantation were smaller than preoperative measurements. Specifically, the difference after Artisan pIOL implantation was -1.07±0.17 mm by A-scan and -0.08±0.08 mm by IOLMaster. The difference after Artiflex pIOL implantation was -1.31±0.15 mm by A-scan and -0.05±0.07 mm by IOLMaster. After Artisan pIOL implantation, differences in AL measurements by A-scan were insignificant (difference: -0.03±0.15 mm), whereas postoperative AL measurements by IOLMaster were significantly longer than preoperative measurements (difference: 0.12±0.07 mm). After Artiflex pIOL implantation, AL measurements by both A-scan and IOLMaster were significantly longer than preoperative measurements (difference: 0.09±0.16 mm by A-scan and 0.07±0.10 mm by IOLMaster). In the Artiflex group, differences in AL measurements by A-scan correlated with the central thickness of the Artiflex pIOL.Conclusion
ACD and AL measurements were influenced by iris-fixated phakic IOL implantation. 相似文献9.
Mahesh Pandit Suman Acharya Ye Gu Sang-Uk Seo Mi-Na Kweon Ben Kang Jae-Hoon Chang 《European journal of immunology》2021,51(6):1461-1472
Blocking the mevalonate pathway for cholesterol reduction by using statin may have adverse effects including statin-induced colitis. Moreover, one of the predisposing factors for colitis is an imbalanced CD4+ T cell, which can be observed on the complete deletion of HMG-CoA reductase (HMGCR), a target of statins. In this study, we inquired geranylgeranyl pyrophosphate (GGPP) is responsible for maintaining the T-cell homeostasis. Following dextran sulfate sodium (DSS)-induced colitis, simvastatin increased the severity of disease, while cotreatment with GGPP, but not with cholesterol, reversed the disease magnitude. GGPP ameliorated DSS-induced colitis by increasing Treg cells. GGPP amplified Treg differentiation through increased IL-2/STAT 5 signaling. GGPP prenylated Ras protein, a prerequisite for extracellular signal-regulated kinase (ERK) pathway activation, leading to increased IL-2 production. Higher simvastatin dose increased the severity of colitis. GGPP ameliorated simvastatin-increased colitis by increasing Treg cells. Treg cells, which have the capacity to suppress inflammatory T cells and were generated through IL-2/STAT5 signaling, increased IL-2 production through prenylation and activation of the Ras/ERK pathway. 相似文献
10.
David Sooik Kim Soo Young Park Beom Kyung Kim Jun Yong Park Do Young Kim Kwang-Hyub Han Yu Rim Lee Won Young Tak Young Oh Kweon Inkyung Jung Minkyung Han Eun Hwa Kim Sang Hoon Ahn Seung Up Kim 《Journal of Korean medical science》2021,36(16)
BackgroundSince September 2015, the initiation of antiviral therapy (AVT) for patients with chronic hepatitis B (CHB)-related cirrhosis has been reimbursed according to the revised Korean Association for the Study of Liver (KASL) guideline, if the patient had hepatitis B virus DNA level ≥ 2,000 IU/L, regardless of aminotransferase or alanine aminotransferase levels. This study investigated whether the KASL guideline implementation reduced the risk of CHB-related hepatocellular carcinoma (HCC) in patients with cirrhosis in South Korea.MethodsA total of 429 patients with CHB-related cirrhosis who initiated AVT between 2014 and 2016 were recruited. The risk of HCC development was compared between patients who initiated AVT before and after September 2015 (pre-guideline [n = 196, 45.7%] vs. post-guideline implementation [n = 233, 54.3%]).ResultsUnivariate analysis showed that AVT initiation before guideline implementation, older age, male gender, and diabetes significantly predicted increased risk of HCC development (all P < 0.05). Subsequent multivariate analysis showed that AVT initiation before guideline implementation (HR = 1.941), older age (HR = 5.762), male gender (HR = 2.555), and diabetes (HR = 1.568) independently predicted increased risk of HCC development (all P < 0.05). Additionally, multivariate analysis showed that AVT initiation before guideline implementation (HR = 2.309), male gender (HR = 3.058), and lower platelet count (HR = 0.989) independently predicted mortality (P < 0.05). The cumulative incidences of HCC and mortality were significantly higher in patients who initiated AVT before guideline implementation than in those who initiated AVT after guideline implementation (all P < 0.05, log-rank test).ConclusionThe prognosis of patients with CHB-related cirrhosis who initiated AVT improved after guideline implementation according to the revised KASL guideline. 相似文献