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      • Delayed differentiation of potent effector CD8<sup>+</sup> T cells reducing viremia and reservoir seeding in acute HIV infection

        Takata, Hiroshi,Buranapraditkun, Supranee,Kessing, Cari,Fletcher, James L. K.,Muir, Roshell,Tardif, Virginie,Cartwright, Pearline,Vandergeeten, Claire,Bakeman, Wendy,Nichols, Carmen N.,Pinyakorn, Sute American Association for the Advancement of Scienc 2017 Science Translational Medicine Vol.9 No.377

        <P>CD8(+) T cells play a critical role in controlling HIV viremia and could be important in reducing HIV-infected cells in approaches to eradicate HIV. The simian immunodeficiency virus model provided the proof of concept for a CD8(+) T cell-mediated reservoir clearance but showed conflicting evidence on the role of these cells to eliminate HIV-infected cells. In humans, HIV-specific CD8(+) T cell responses have not been associated with a reduction of the HIV-infected cell pool in vivo. We studied HIV-specific CD8(+) T cells in the RV254 cohort of individuals initiating ART in the earliest stages of acute HIV infection (AHI). We showed that the HIV-specific CD8(+) T cells generated as early as AHI stages 1 and 2 before peak viremia are delayed in expanding and acquiring effector functions but are endowed with higher memory potential. In contrast, the fully differentiated HIV-specific CD8(+) T cells at peak viremia in AHI stage 3 were more prone to apoptosis but were associated with a steeper viral load decrease after ART initiation. Their capacity to persist in vivo after ART initiation correlated with a lower HIV DNA reservoir. These findings demonstrate that HIV-specific CD8(+) T cell magnitude and differentiation are delayed in the earliest stages of infection. These results also demonstrate that potent HIV-specific CD8(+) T cells contribute to the reduction of the pool of HIV-producing cells and the HIV reservoir seeding in vivo and provide the rationale to design interventions aiming at inducing these potent responses to cure HIV infection.</P>

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        The Effect of STW5 (Iberogast) on Reflux Symptoms in Patients With Concurrent Dyspeptic Symptoms: A Double-blind Randomized Placebo-controlled Crossover Trial

        Renske A B Oude Nijhuis,Thijs Kuipers,Jac M Oors,Thomas V K Herregods,Boudewijn F Kessing,Jeroen M Schuitenmaker,Andreas J P M Smout,Albert J Bredenoord 대한소화기 기능성질환∙운동학회 2024 Journal of Neurogastroenterology and Motility (JNM Vol.30 No.1

        Background/AimsIt has been suggested that STW5 (Iberogast) reduces heartburn symptoms in patients with functional dyspepsia, but underlying mechanisms of action are unclear. The aim of this study is to investigate whether STW5 affects esophageal sensitivity or esophageal motility, thereby reducing occurrence and perception of reflux events. MethodsWe performed a double-blind, randomized, placebo-controlled, crossover trial in patients with functional dyspepsia (Rome IV) and reflux symptoms. After 4 weeks of treatment with either placebo or STW5, patients were studied with an esophageal acid perfusion test and ambulatory 24-hour pH-impedance monitoring. ResultsA total of 18 patients (7 men, median age 54, range [19-76]), were included in the study. Although we found no statistical difference in our primary outcome the total Reflux Disease Questionnaire score 2.33 (0.25-4.33) vs 2.67 (1.17-4.00), P = 0.347, “gastroesophageal reflux disease” and “regurgitation” subscale scores were lower after STW5 treatment compared to placebo (P = 0.049 and P = 0.007). There was no statistical difference in number of reflux events, acid exposure time and acid sensitivity scores between STW5 and placebo. In a subgroup analysis of patients with pH-metry confirmed gastroesophageal reflux disease, treatment with STW5 significantly reduced the total number of acidic reflux events (P = 0.028). Moreover, in patients with reflux esophagitis, the median lag time to acid perception increased after STW5 treatment (P = 0.042). ConclusionsWe found some indications pointing towards a beneficial effect of STW5 on reflux symptoms in dyspeptic patients, with reduction of esophageal hypersensitivity as a potential underlying mechanism. Our findings will have to be confirmed in larger studies.

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        Psycholinguistic Evidence for Laterality Preferences and Information Processing in Japanese

        Kess, Joseph F.,Tadao Miyamoto 서울대학교 어학연구소 1996 語學硏究 Vol.32 No.2

        The human brain exhibits hemispheric differences in information processing functions, and this fact of laterality preferences is reflected in language processing functions which involve lexical access and written word recognition in Japanese. This paper evaluates the Japanese psycholinguistic literature in the areas of experimental psycology and clinical aphasiology in an attempt to ascertain whether Japanese in unique in its characteristic pattern of laterality preferences in information processing tasks which involve its syllabary (Kana) and Chinese character (Kanji) orthographic representations. This paper also addresses misperceptions regarding lateralization and hemispheric preferences in processing Japanese orthographic types, since purported differences in lateralization can be uncritically accepted as underlying factors in not only language processing, but can also find their way into Nihonjinron discussions if differences in mental attitude and philosophical outlook.

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        Improved oral bioavailability of capsaicin via liposomal nanoformulation: preparation, in vitro drug release and pharmacokinetics in rats

        Yuan Zhu,Miaomiao Wang,Jiajia Zhang,Wei Peng,Caleb Kesse Firempong,Wenwen Deng,Qilong Wang,Shicheng Wang,Feng Shi,Jiangnan Yu,Ximing Xu,Weiming Zhang 대한약학회 2015 Archives of Pharmacal Research Vol.38 No.4

        This study innovatively prepared an effectivecapsaicin-loaded liposome, a nanoformulation with fewerirritants, for oral administration. The in vitro and in vivoproperties of the liposomal encapsulation were investigatedand the potential possibility of oral administration evaluated. The liposomal agent composed of phospholipid, cholesterol,sodium cholate and isopropyl myristate was prepared usingfilm-dispersion method. A level A in vitro–in vivo correlation(IVIVC) was established for the first time, which demonstratedan excellent IVIVC of both formulated and freecapsaicin in oral administration. Physicochemical characterizationsincluding mean particle size, zeta (f) potentialand average encapsulation efficiency of capsaicin-loadedliposome were found to be 52.2 ± 1.3 nm, -41.5 ±2.71 mv and 81.9 ± 2.43 %, respectively. In vivo, liposomalencapsulation allowed a 3.34-fold increase in relativebioavailability compared to free capsaicin. The gastricmucosa irritation studies indicated that the liposomal systemwas a safe carrier for oral administration. These resultssupport the fact that capsaicin, an effective drug for thetreatment of neuropathic pain, could be encapsulated inliposome for improved oral bioavailability. The excellentIVIVC of capsaicin-loaded liposome could also be a promisingtool in liposomal formulation development with anadded advantage of reduced animal testing.

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