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Kim, Youngsoo,Kim, Seong Hun,Kim, Kook Hwan,Chae, Sujin,Kim, Chanki,Kim, Jeongjin,Shin, Hee-Sup,Lee, Myung-Shik,Kim, Daesoo IRL Press 2015 Human molecular genetics Vol.24 No.25
<P>Really interesting new gene (RING) finger protein 170 (RNF170) is an E3 ubiquitin ligase known to mediate ubiquitination-dependent degradation of type-I inositol 1,4,5-trisphosphate receptors (ITPR1). It has recently been demonstrated that a point mutation of <I>RNF170</I> gene is linked with autosomal-dominant sensory ataxia (ADSA), which is characterized by an age-dependent increase of walking abnormalities, a rare genetic disorder reported in only two families. Although this mutant allele is known to be dominant, the functional identity thereof has not been clearly established. Here, we generated mice lacking <I>Rnf170</I> (<I>Rnf170<SUP>−/−</SUP></I>) to evaluate the effect of its loss of function <I>in vivo</I>. Remarkably, <I>Rnf170<SUP>−/−</SUP></I> mice began to develop gait abnormalities in old age (12 months) in the form of asynchronous stepping between diagonal limb pairs with a fixed step sequence during locomotion, while age-matched wild-type mice showed stable gait patterns using several step sequence repertoires. As reported in ADSA patients, they also showed a reduced sensitivity for proprioception and thermal nociception. Protein blot analysis revealed that the amount of Itpr1 protein was significantly elevated in the cerebellum and spinal cord but intact in the cerebral cortex in <I>Rnf170<SUP>−/−</SUP></I> mice. These results suggest that the loss of <I>Rnf170</I> gene function mediates ADSA-associated phenotypes and this gives insights on the cure of patients with ADSA and other age-dependent walking abnormalities.</P>
Kim, Jeongjin,Woo, Jeonghoon,Park, Young-Gyun,Chae, Sujin,Jo, Seonmi,Choi, Jeong Woo,Jun, Hong Young,Yeom, Young Il,Park, Seong Hoon,Kim, Kyung Hwan,Shin, Hee-Sup,Kim, Daesoo The Society 2011 The Journal of neuroscience Vol.31 No.11
<P>Hypoxic damage to the prefrontal cortex (PFC) has been implicated in the frontal lobe dysfunction found in various neuropsychiatric disorders. The underlying subcortical mechanisms, however, have not been well explored. In this study, we induced a PFC-specific hypoxia-like damage by cobalt-wire implantation to demonstrate that the role of the mediodorsal thalamus (MD) is critical for the development of frontal lobe dysfunction, including frontal lobe-specific seizures and abnormal hyperactivity. Before the onset of these abnormalities, the cross talk between the MD and PFC nuclei at theta frequencies was enhanced. During the theta frequency interactions, burst spikes, known to depend on T-type Ca(2+) channels, were increased in MD neurons. In vivo knockout or knockdown of the T-type Ca(2+) channel gene (Ca(V)3.1) in the MD substantially reduced the theta frequency MD-PFC cross talk, frontal lobe-specific seizures, and locomotor hyperactivity in this model. These results suggest a two-step model of prefrontal dysfunction in which the response to a hypoxic lesion in the PFC results in abnormal thalamocortical feedback driven by thalamic T-type Ca(2+) channels, which, in turn, leads to the onset of neurological and behavioral abnormalities. This study provides valuable insights into preventing the development of neuropsychiatric disorders arising from irreversible PFC damage.</P>
GIT1 is associated with ADHD in humans and ADHD-like behaviors in mice
Won, Hyejung,Mah, Won,Kim, Eunjin,Kim, Jae-Won,Hahm, Eun-Kyoung,Kim, Myoung-Hwan,Cho, Sukhee,Kim, Jeongjin,Jang, Hyeran,Cho, Soo-Churl,Kim, Boong-Nyun,Shin, Min-Sup,Seo, Jinsoo,Jeong, Jaeseung,Choi, S Nature Publishing Group, a division of Macmillan P 2011 Nature medicine Vol.17 No.5
Attention deficit hyperactivity disorder (ADHD) is a psychiatric disorder that affects ??% of school-aged children; however, the mechanisms underlying ADHD remain largely unclear. Here we report a previously unidentified association between G protein??coupled receptor kinase??interacting protein-1 (GIT1) and ADHD in humans. An intronic single-nucleotide polymorphism in GIT1, the minor allele of which causes reduced GIT1 expression, shows a strong association with ADHD susceptibility in humans. Git1-deficient mice show ADHD-like phenotypes, with traits including hyperactivity, enhanced electroencephalogram theta rhythms and impaired learning and memory. Hyperactivity in Git1<SUP>??/??</SUP> mice is reversed by amphetamine and methylphenidate, psychostimulants commonly used to treat ADHD. In addition, amphetamine normalizes enhanced theta rhythms and impaired memory. GIT1 deficiency in mice leads to decreases in ras-related C3 botulinum toxin substrate-1 (RAC1) signaling and inhibitory presynaptic input; furthermore, it shifts the neuronal excitation-inhibition balance in postsynaptic neurons toward excitation. Our study identifies a previously unknown involvement of GIT1 in human ADHD and shows that GIT1 deficiency in mice causes psychostimulant-responsive ADHD-like phenotypes.
Kim, Eun Ae,Yoo, Shinjung,Kim, Jeongjin The Korean Fiber Society 2003 Fibers and polymers Vol.4 No.4
A vertical skin model with two detachable environmental chambers was developed to simulate a Human-Clothing-Environment system and to evaluate heat and moisture transport properties of textile materials under severe conditions and during transient states. The construction of the system was described and data reproducibility and accuracy of the instrument were verified by using PEG treated nonwovens. Also advantages over a traditional static type experiment were demonstrated based on a series of experiments.
Kim Dong Wook,Ahn Hyemin,Kim Kyung Won,Lee Seung Soo,Kim Hwa Jung,Ko Yousun,Park Taeyong,Lee Jeongjin 대한영상의학회 2022 Korean Journal of Radiology Vol.23 No.11
Objective: The clinical relevance of myosteatosis has not been well evaluated in patients with pancreatic ductal adenocarcinoma (PDAC), although sarcopenia has been extensively researched. Therefore, we evaluated the prognostic value of muscle quality, including myosteatosis, in patients with resectable PDAC treated surgically. Materials and Methods: We retrospectively evaluated 347 patients with resectable PDAC who underwent curative surgery (mean age ± standard deviation, 63.6 ± 9.6 years; 202 male). Automatic muscle segmentation was performed on preoperative computed tomography (CT) images using an artificial intelligence program. A single axial image of the portal phase at the inferior endplate level of the L3 vertebra was used for analysis in each patient. Sarcopenia was evaluated using the skeletal muscle index, calculated as the skeletal muscle area (SMA) divided by the height squared. The mean SMA attenuation was used to evaluate myosteatosis. Diagnostic cutoff values for sarcopenia and myosteatosis were devised using the Contal and O’Quigley methods, and patients were classified according to normal (nMT), sarcopenic (sMT), myosteatotic (mMT), or combined (cMT) muscle quality types. Multivariable Cox regression analyses were conducted to assess the effects of muscle type on the overall survival (OS) and recurrence-free survival (RFS) after surgery. Results: Eighty-four (24.2%), 73 (21.0%), 75 (21.6%), and 115 (33.1%) patients were classified as having nMT, sMT, mMT, and cMT, respectively. Compared to nMT, mMT and cMT were significantly associated with poorer OS, with hazard ratios (HRs) of 1.49 (95% confidence interval, 1.00–2.22) and 1.68 (1.16–2.43), respectively, while sMT was not (HR of 1.40 [0.94–2.10]). Only mMT was significantly associated with poorer RFS, with an HR of 1.59 (1.07–2.35), while sMT and cMT were not. Conclusion: Myosteatosis was associated with poor OS and RFS in patients with resectable PDAC who underwent curative surgery.
Reliability of Skeletal Muscle Area Measurement on CT with Different Parameters: A Phantom Study
Kim Dong Wook,Ha Jiyeon,Ko Yousun,Kim Kyung Won,Park Taeyong,Lee Jeongjin,You Myung-Won,Yoon Kwon-Ha,Park Ji Yong,Kee Young Jin,Kim Hong-Kyu 대한영상의학회 2021 Korean Journal of Radiology Vol.22 No.4
Objective: To evaluate the reliability of CT measurements of muscle quantity and quality using variable CT parameters. Materials and Methods: A phantom, simulating the L2–4 vertebral levels, was used for this study. CT images were repeatedly acquired with modulation of tube voltage, tube current, slice thickness, and the image reconstruction algorithm. Reference standard muscle compartments were obtained from the reference maps of the phantom. Cross-sectional area based on the Hounsfield unit (HU) thresholds of muscle and its components, and the mean density of the reference standard muscle compartment, were used to measure the muscle quantity and quality using different CT protocols. Signal-to-noise ratios (SNRs) were calculated in the images acquired with different settings. Results: The skeletal muscle area (threshold, -29 to 150 HU) was constant, regardless of the protocol, occupying at least 91.7% of the reference standard muscle compartment. Conversely, normal attenuation muscle area (30–150 HU) was not constant in the different protocols, varying between 59.7% and 81.7% of the reference standard muscle compartment. The mean density was lower than the target density stated by the manufacturer (45 HU) in all cases (range, 39.0–44.9 HU). The SNR decreased with low tube voltage, low tube current, and in sections with thin slices, whereas it increased when the iterative reconstruction algorithm was used. Conclusion: Measurement of muscle quantity using HU threshold was reliable, regardless of the CT protocol used. Conversely, the measurement of muscle quality using the mean density and narrow HU thresholds were inconsistent and inaccurate across different CT protocols. Therefore, further studies are warranted in future to determine the optimal CT protocols for reliable measurements of muscle quality.
Kim, Ok-Kyung,Lee, Minhee,Kwon, Han Ol,Lee, Dasom,Park, Jeongjin,Kim, Eungpil,You, Yanghee,Lim, Young Tae,Jun, Woojin,Lee, Jeongmin S. Karger AG 2018 Skin pharmacology and physiology Vol.31 No.4
<P>We investigated the potential effects of<I> Costaria costata</I><B><I></I></B> (CC) on atopic dermatitis (AD) development in chloro-2,4-dinitrobenzene (DNCB)-treated NC/Nga mice. CC is a brown alga distributed across the seas of Korea, China, and Japan. A total of 40 mice were randomly assigned to 5 groups with 8 mice per group: untreated Balb/c mice, AD control (0.1% w/v DNCB-treated NC/Nga mice), positive control (i.e., DNCB-treated NC/Nga mice fed a dietary supplement of 66.6 mg/kg of body weight [b.w.] of CJLP133), DNCB-treated NC/Nga mice fed a dietary supplement of 100 mg/kg b.w. of CCE10 (CCE10 100), and DNCB-treated mice fed a dietary supplement of 300 mg/kg b.w. of CCE10 (CCE10 300) groups. The CCE10 100 and CCE10 300 treatment groups suppressed AD development including clinical and histopathological changes and a reduction in skin hydration induced by DNCB. In addition, Th2 cytokine production in primary splenocytes, serum IgE and histamine production, and mast cell infiltration into the skin were suppressed in the CCE10 300 mice compared to the CCE10 100 mice. Our finding demonstrated an inhibitory effect of CCE10 in AD development by means of improving the Th1/Th2 cytokine balance and anti-inflammatory effect in an in vivo model.</P>