Significance
T
H
17 cells are a subset of CD4
+
T helper cells that secrete the cytokine IL-17 and play a role in autoimmunity. RORγt is identified as a key transcription factor driving the T
H
17 ...differentiation. Sequence analysis indicated that transcription factor contains several conserved DNA-binding domain and isotype-specific domain that we termed transcription modulation domain (TMD). We designed a novel therapeutics, tRORγt-TMD, to deliver RORγt-TMD efficiently into the nucleus of the cells that regulates T
H
17 cell functions and T
H
17-mediated autoimmune diseases. With the same concept, tTbet-TMD also can regulate T
H
1 functions. In conclusion, tRORγt-TMD/tTbet-TMD can be novel and highly specific therapeutics for the treatment of T
H
17/T
H
1-mediated inflammatory disease and further allows us to discover new function of RORγt/Tbet in animals without genetic alteration.
The nuclear hormone receptor retinoic acid-related orphan receptor gamma t (RORγt) is a transcription factor (TF) specific to T
H
17 cells that produce interleukin (IL)-17 and have been implicated in a wide range of autoimmunity. Here, we developed a novel therapeutic strategy to modulate the functions of RORγt using cell-transducible form of transcription modulation domain of RORγt (tRORγt-TMD), which can be delivered effectively into the nucleus of cells and into the central nerve system (CNS). tRORγt-TMD specifically inhibited T
H
17-related cytokines induced by RORγt, thereby suppressing the differentiation of naïve T cells into T
H
17, but not into T
H
1, T
H
2, or T
reg
cells. tRORγt-TMD injected into experimental autoimmune encephalomyelitis (EAE) animal model can be delivered effectively in the splenic CD4
+
T cells and spinal cord-infiltrating CD4
+
T cells, and suppress the functions of T
H
17 cells. The clinical severity and incidence of EAE were ameliorated by tRORγt-TMD in preventive and therapeutic manner, and significant reduction of both infiltrating CD4
+
IL-17
+
T cells and inflammatory cells into the CNS was observed. As a result, the number of spinal cord demyelination was also reduced after tRORγt-TMD treatment. With the same proof of concept, tTbet-TMD specifically blocking T
H
1 differentiation improved the clinical incidence of rheumatoid arthritis (RA). Therefore, tRORγt-TMD and tTbet-TMD can be novel therapeutic reagents with the natural specificity for the treatment of inflammatory diseases associated with T
H
17 or T
H
1. This strategy can be applied to treat various diseases where a specific transcription factor has a key role in pathogenesis.
The nuclear hormone receptor retinoic acid-related orphan receptor gamma t (ROR...t) is a transcription factor (TF) specific to ... cells that produce interleukin (IL)-17 and have been implicated in ...a wide range of autoimmunity. Here, we developed a novel therapeutic strategy to modulate the functions of ROR...t using cell-transducible form of transcription modulation domain of ROR...t (tROR...t-TMD), which can be delivered effectively into the nucleus of cells and into the central nerve system (CNS). tROR...t-TMD specifically inhibited ...-related cytokines induced by ROR...t, thereby suppressing the differentiation of naive T cells into ..., but not into ..., ..., or Treg cells. tROR...t-TMD injected into experimental autoimmune encephalomyelitis (EAE) animal model can be delivered effectively in the splenic CD4+ T cells and spinal cord-infiltrating CD4+ T cells, and suppress the functions of ... cells. The clinical severity and incidence of EAE were ameliorated by tROR...t-TMD in preventive and therapeutic manner, and significant reduction of both infiltrating CD4+ IL-17+ T cells and inflammatory cells into the CNS was observed. As a result, the number of spinal cord demyelination was also reduced after tROR...t-TMD treatment. With the same proof of concept, tTbet-TMD specifically blocking ... differentiation improved the clinical incidence of rheumatoid arthritis (RA). Therefore, tROR...t-TMD and tTbet-TMD can be novel therapeutic reagents with the natural specificity for the treatment of inflammatory diseases associated with ... or ... This strategy can be applied to treat various diseases where a specific transcription factor has a key role in pathogenesis. (ProQuest: ... denotes formulae/symbols omitted.)
Purpose
The purpose of this study was to evaluate the diagnostic efficacy of acoustic structure quantification (ASQ) parameters mode, average, and focal distribution (FD) ratio in the staging of ...hepatic fibrosis in patients with chronic viral hepatitis and to compare it with transient elastography (TE) by using liver biopsy as reference standard.
Methods
We studied 62 patients with chronic viral hepatitis. Each patient underwent ASQ evaluation and liver biopsy; 54 of these patients received TE. Thirty-six participants without any liver disease were enrolled as normal group, who also underwent ASQ evaluation and TE. All three parameters of ASQ were compared with the histologic fibrosis grade according to the METAVIR scoring (F0–F4). Statistical analysis was performed to investigate the correlations and the diagnostic values of ASQ parameters and compare them to TE.
Results
All three ASQ parameters and TE were significantly correlated with liver fibrosis stage. Of the ASQ parameters, the mode parameter showed the best correlation (
P
< 0.001). On the area under the receiver operating characteristic curve (AUROC), the mode parameter of ASQ analysis showed both significant correlation and good accuracy for diagnosis of
F
≥ 1,
F
≥ 2, and
F
≥ 3. These values were significantly better than those of the average and FD ratio parameters in
F
≥ 1 and
F
≥ 2 (
P
< 0.05). There was no statistically significant difference in AUROC between the mode parameter and TE in diagnosis of
F
≥ 1,
F
≥ 2, or
F
≥ 3.
Conclusions
The mode parameter is the most reliable ASQ parameter, comparable to TE, as a non-invasive method for the detection and grading of liver fibrosis in patients with chronic viral hepatitis.
Although amyloid PET of typical Alzheimer's disease (AD) shows diffuse ß-amyloid (Aß) deposition, some patients show focal deposition. The clinical significance of this focal Aß is not well ...understood. We examined the clinical significance of focal Aß deposition in terms of cognition as well as Aß and tau cerebrospinal fluid (CSF) levels. We further evaluated the order of Aß accumulation by visual assessment.
We included 310 subjects (125 cognitively unimpaired, 125 mild cognitive impairment, and 60 AD dementia) from 9 referral centers. All patients underwent neuropsychological tests and
F-flutemetamol (FMM) PET. Seventy-seven patients underwent CSF analysis. Each FMM scan was visually assessed in 10 regions (frontal, precuneus and posterior cingulate, lateral temporal, parietal, and striatum of each hemisphere) and was classified into three groups: No-FMM, Focal-FMM (FMM uptake in 1-9 regions), and Diffuse-FMM (FMM uptake in all 10 regions).
53/310 (17.1%) subjects were classified as Focal-FMM. The cognitive level of the Focal-FMM group was better than that of Diffuse-FMM group and worse than that of No-FMM group. Among the Focal-FMM group, those who had FMM uptake to a larger extent or in the striatum had worse cognitive levels. Compared to the Diffuse-FMM group, the Focal-FMM group had a less AD-like CSF profile (increased Aß42 and decreased t-tau, t-tau/Aß42). Among the Focal-FMM group, Aß deposition was most frequently observed in the frontal (62.3%) and least frequently observed in the striatum (43.4%) and temporal (39.6%) regions.
We suggest that focal Aß deposition is an intermediate stage between no Aß and diffuse Aß deposition. Furthermore, among patients with focal Aß deposition, those who have Aß to a larger extent and striatal involvement show clinical features close to diffuse Aß deposition. Further longitudinal studies are needed to evaluate the disease progression of patients with focal Aß deposition.
Together with the growing emphasis on knowledge intensive service (KIS), KOTEC (Korea Technology Finance Corporation) has set KIS as the main industry domain for technology financing. However, the ...perception gap in the definition of ‘Technology’ and ‘Knowledge’ could be a constraint for funding KIS. In this study, through a survey to companies in Korea that can be possible beneficiaries of technology funding, authors have identified the existence of such constraint, and also have suggested some ways for institutional improvements of such constraint.
The aim of this study was to evaluate the accuracy of 3-T magnetic resonance imaging (MRI) in locating rectal cancer, and to determine whether tumor location correlates with the incidence of ...pulmonary metastasis.
A total of 146 patients with confirmed rectal adenocarcinoma underwent 3-T rectal MRI, and abdominal and chest computed tomography (CT) within 2 weeks of the endoscopic examination. We reviewed the distance between the mass and the anal verge recorded in the endoscopic reports of these patients. Two radiologists evaluated the same distance on MRI scans by using picture archiving and communications systems. Multiple factors including the tumor location, primary tumor and lymph node stage, lung and liver metastasis, pathologic differentiation, and the carcinoembryonic antigen level were evaluated. The correlation between tumor location on MRI and endoscopy was assessed, and significant factors influencing pulmonary metastasis were identified using multivariate logistic regression analysis.
There was a statistically significant correlation between the tumor location established using MRI and the actual location recorded during endoscopy. The incidence of pulmonary metastasis was significantly higher in patients with lower rectal cancer (11/17, 65%) compared to those with upper rectal cancer (6/17, 35%; p<0.05). Factors associated with pulmonary metastasis were tumor location and the presence of liver metastasis.
The accurate tumor location could be indicated using 3-T rectal MRI. Pulmonary metastasis occurred more frequently in patients with lower rectal cancer than in those with upper rectal cancer.
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