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Epigenomic Alteration in Replicative Senescent-mesenchymal Stem Cells (중간엽줄기세포의 노화에 따른 후생유전학적 변화)

  • Oh, Youn Seo;Cho, Goang-Won
    • Journal of Life Science
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    • v.25 no.6
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    • pp.724-731
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    • 2015
  • Mesenchymal stem cells (MSCs) are characterized by their multipotency capacity, which allows them to differentiate into diverse cell types (bone, cartilage, fat, tendon, and neuron-like cells) and secrete a variety of trophic factors (ANG, FGF-2, HGF, IGF-1, PIGF, SDF-1α, TGF-β, and VEGF). MSCs can be easily isolated from human bone-marrow, fat, and umbilical-cord tissues. These features indicate that MSCs might be of use in stem-cell therapy. However, MSCs undergo cellular senescence during long-term expansion, and this is accompanied by functional declines in stem-cell potency. In the human body, because of their senescence and declines in their microenvironmental niches stem cells fail to maintain tissue homeostasis, and as a result, senescent cells accumulate in tissues. This can lead to age-related diseases, including degenerative disorders and cancers. Recent studies suggest that the number of histone modifications to stem cells’ genomes and aberrant alterations to their DNA methylation increase as stem cells progress into senescence. These epigenetic alterations have been partly reversed with treatments in which DNA methyltransferase (DNMT) inhibitors or histone deacetylase (HDAC) inhibitors are introduced into replicative senescent-MSCs. This review focuses on epigenetic alteration in replicative senescent-MSCs and explains how epigenetic modifications are widely associated with stem-cell senescences such as differentiation, proliferation, migration, calcium signaling, and apoptosis.

Painful Channels in Sensory Neurons

  • Lee, Yunjong;Lee, Chang-Hun;Oh, Uhtaek
    • Molecules and Cells
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    • v.20 no.3
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    • pp.315-324
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    • 2005
  • Pain is an unpleasant sensation experienced when tissues are damaged. Thus, pain sensation in some way protects body from imminent threat or injury. Peripheral sensory nerves innervated to peripheral tissues initially respond to multiple forms of noxious or strong stimuli, such as heat, mechanical and chemical stimuli. In response to these stimuli, electrical signals for conducting the nociceptive neural signals through axons are generated. These action potentials are then conveyed to specific areas in the spinal cord and in the brain. Sensory afferent fibers are heterogeneous in many aspects. For example, sensory nerves are classified as $A{\alpha}$, $-{\beta}$, $-{\delta}$ and C-fibers according to their diameter and degree of myelination. It is widely accepted that small sensory fibers tend to respond to vigorous or noxious stimuli and related to nociception. Thus these fibers are specifically called nociceptors. Most of nociceptors respond to noxious mechanical stimuli and heat. In addition, these sensory fibers also respond to chemical stimuli [Davis et al. (1993)] such as capsaicin. Thus, nociceptors are considered polymodal. Recent advance in research on ion channels in sensory neurons reveals molecular mechanisms underlying how various types of stimuli can be transduced to neural signals transmitted to the brain for pain perception. In particular, electrophysiological studies on ion channels characterize biophysical properties of ion channels in sensory neurons. Furthermore, molecular biology leads to identification of genetic structures as well as molecular properties of ion channels in sensory neurons. These ion channels are expressed in axon terminals as well as in cell soma. When these channels are activated, inward currents or outward currents are generated, which will lead to depolarization or hyperpolarization of the membrane causing increased or decreased excitability of sensory neurons. In order to depolarize the membrane of nerve terminals, either inward currents should be generated or outward currents should be inhibited. So far, many cationic channels that are responsible for the excitation of sensory neurons are introduced recently. Activation of these channels in sensory neurons is evidently critical to the generation of nociceptive signals. The main channels responsible for inward membrane currents in nociceptors are voltage-activated sodium and calcium channels, while outward current is carried mainly by potassium ions. In addition, activation of non-selective cation channels is also responsible for the excitation of sensory neurons. Thus, excitability of neurons can be controlled by regulating expression or by modulating activity of these channels.

Radiotherapy Results of Stage I Glottic Cancer (조기 성문암의 방사선 치료 결과)

  • Kim, Jae-Chul;Park, In-Kyu
    • Radiation Oncology Journal
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    • v.16 no.3
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    • pp.245-250
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    • 1998
  • Purpose : This study was to evaluate survival, failure patterns, and prognostic factors of stage I squamous cell carcinoma of the glottic larynx after curative radiation therapy. Materials and Methods : A retrospective analysis was done for 57 patients with glottic cancer who were treated with curative radiation therapy from June 1985 to November 1992. There were 55 male and two female patients. Patients' age ranged from 17 to 71 years(median 39 years). Radiation therapy was delivered five times a week, 2 Gy daily, total 66 Gy using 6 MV X-ray. Results : Complete response(CR) was noted in 51 out of 57 patients (89.5%) and persistent disease (PER) in six out of 57 patients(10.5%). The disease-free survival rates at 3 and 5 years were 72.9% and 63.8%, respectively. Seven failures were observed among 51 CR patients during follow-up. Salvage total laryngectomy for six recurred patients and partial laryngectomy for one recurred patient were done with successful results, i.e., all of them were actually salvaged. Among six PER patients, salvage total laryngectomy for two patients and partial laryngectomy for two patients were done and two patients refused operation. Following salvage surgery for the four PER patients, three were salvaged and one failed locoregionally. Among the 13 failures 10(76.9%) were salvaged with surgery. The ultimate local control rate at 5 years was 92.3% and overall 47 out of 57 (82.5%) patients were able to preserve their larynx. The 5-year disease-free survival rates were 85.5% for posterior lesions, and 61.6% for anterior lesions(P<0.05). Cord mobility, involvement of anterior commissure, field size, and T stage did not impact on disease-free survival. Conclusion : Considering the high percentage of voice preservation with initial radiotherapy, radiotherapy should be the first choice in the treatment of stage 1 glottic carcinoma.

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Role of Posterior Intralaminar Thalamic Nuclei in Acupuncture Analgesia in Rats (침진통(鍼鎭痛) 작용에 있어서 시상 후방 층판내핵(속방핵)의 역할)

  • Roh, Sik;Min, Byung-Il;Yoon, Sang-Hyub
    • The Journal of Korean Medicine
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    • v.20 no.3 s.39
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    • pp.36-44
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    • 1999
  • Objectives: It has been well known that electroacupuncture(EA) has an analgesic effect and there is a pain control system in the central nervous system(CNS). The pain control system is composed of three major nuclei, which are periaqueductal gray(PAG), raphe nuclei, and the pain inhibitory complex located in the spinal cord. It has been suggested that the analgesic effect of EA might be the result of activation of the pain control system in the CNS. However, there may be a possibility that other nuclei are also involved in this pain modulation. Thus, we investigated whether the posterior intralaminar thalamic nuclei (PTIN) are involved in the pain modulation. Methods: To measure the level of pain, the jaw opening reflex (JOR) was used as a pain index. The magnitude of JOR is estimated by averaging the area of 10 successive responses. JOR was evoked by tooth-pulp stimulation with bipolar electrode carrying stimulus with the following parameters: intensity ranging from 420uA to 680ulA, 0.3ms duration of square pulse, and 0.5 Hz. Hapkog($LI_4$) and Taechung ($LR_3$) were the chosen acupoints. The Hapkog point was stimulated ipsilaterally at 5V, 3 Hz, for 15min in total, and the Taechung was stimulated at 2-3 V, 3 Hz, and for a total of 15 or 30 minutes. Different intensities of stimulation were given the PITN; one was given at $300{\mu}A$ and the other was at 500uA. The position stimulated in these nuclei by Paxinos Atlas was AP; from bregma $-4.0{\sim}-4.3mm,\;L; 0.5{\sim}1.8mm,\;D;\;4.8{\sim}6.3mm$. Results: The Hapkog point had a significant analgesic effect (P<0.05). However, the Taechung point had no effect. Both types of stimulation in the PITN did not reveal any analgesic effects. Conclusions: From these results, it was suggested that the posterior intralaminar thalamic nuclei are not involved in the modulation of pain.

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Experience with the Application of Magnetic Resonance Diagnostic $Analyser^{(R)}$ -A case of reflex sympathetic dystrophy- (자기공명분석기에 의한 반사성 교감신경성 위축증의 치험)

  • Kim, Jin-Soo;Kwak, Su-Dal;Kim, Jun-Soon;Ok, Sy-Young;Cha, Young-Deog;Park, Wook
    • The Korean Journal of Pain
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    • v.6 no.2
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    • pp.275-279
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    • 1993
  • Reflex sympathetic dystrophy is a syndrome characterized by persistent, burning pain, hyperpathia, allodynia & hyperaesthesia in an extremity, with concurrent evidence of autonomic nervous system dysfunction. It generally develops after nerve injury, trauma, surgery, et al. The most successful therapies are directed towards blocking the sympathetic intervention to the affected extremity by regional sympathetic ganglion block or Bier block with sympathetic blocker; other traditional treatments include transcutaneous electrical stimulation, immobilization with cast & splint, physical therapy, psychotherapy, administration of sympathetic blocker, calcitonin, corticosteroid and analgesic agents. The purpose of this report is to evaluate and describe the effects of magnetic resonance following unsatisfactory results with traditional treatments of RSD. A 17 year old female patient, 1 year earlier, had received excision and drainage of pus at the right femoral triangle due to an injury caused by a stone. Afterwards, she experienced burning pain, knee joint stiffness, and muscle dystrophy of the right thigh, especially when standing and walking. Despite a year of number of traditional treatments such as: lumbar sympathetic block, continuous epidural analgesia, transcutaneous electrical stimulation, & administration of predisolone, her pain did not improve. Surprisingly, the patients was able to walk free from pain and difficulty after just one application of magnetic resonance. The patient has been successfully treated with further treatment of two to three times a week for approximately ten weeks. More recently, magnetic resonance has been demonstrated to produce effective results for the relief of pain in a variety of diseases. From our experiences we recognize magnetic resonance as a therapeutic modality which can provide excellent results for the treatment of RSD. It has been suggested that polysynaptic reflex which are disturbed in RSD may be modulated normally on the spinal cord level through the application of magnetic resonance.

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Spinal Co-Administration of Ginsenosides with Morphine Prevents the Development of Opioid Tolerance and Attenuates Opioid Dependence

  • Choi Seok;Jung Se-Yeon;Nah Jin-Ju;Ahn Eun-Soon;Kim Yoon-Hee;Nam Ki-Yeul;Kim Seok-Chang;Ko Sung-Ryong;Rhim Hyewhon;Nah Seung-Yeol
    • Journal of Ginseng Research
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    • v.23 no.4
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    • pp.239-246
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    • 1999
  • The analgesic effect of ginsenosides or morphine was determined following intrathecal (i.t.) administration in rat tail-flick test. The effects of intrathecal co-administration of ginsenosides with morphine on the development of opioid tolerance and dependence were also examined using rat tail-flick test and naloxone-pre-cipitated withdrawal, respectively. Administration of ginsenosides (i.t.) produced a weak antinociception in a dose-dependent manner. Administration of morphine (i.t.) also produced antinociception in a dose-dependent manner. The $ED_50$ was $1.20\;{\mu}g\;(1.14\~1.29\;{\mu}g)$. However, the acute co-administration of $200{\mu}g$ ginsenosides with 0.1-1.0${\mu}g$ morphine did not show additive effect on morphine induced analgesia in rat tail-flick test. I.t. co-administration of 200 ${\mu}g$ ginsenosides with 10 ${\mu}g$ morphine for 7 days inhibited development of tolerance induced by 10 ${\mu}g$ morphine in rat tail-flick test, although i.t. co-administration of 50 or 100 ${\mu}g$ ginsenosides with morphine was without effect. I.t. co-administration of 200 ${\mu}g$ ginsenosides for 7 days also partially attenuated the development of morphine dependence as assessed by naloxone-precipitated withdrawal. In conclusion, these results suggest that i.t. administered ginsenosides produce a weak antinociception in rat tail-flick test and also prevent opioid tolerance and attenuate opioid dependence in chronic treatment with morphine at the spinal sites.

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Involvement of Serine Phosphorylation of Spinal Cord NR-2B Subunit of the N-methyl-D-aspartate Receptor Following Electroacupuncture Stimulation (전침자극이 척수 N-methy1-D-aspartate receptor외 NR-2B Subunit 인산화에 미치는 영향)

  • Kang, Byeol-Rim;Choi, Byung-Tae;Yoon, Hyun-Min;Min, Young-Kwang;Ahn, Chang-Beohn
    • Journal of Acupuncture Research
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    • v.24 no.2
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    • pp.63-71
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    • 2007
  • 목적 : 저주파에 해당하는 2Hz 전침 자극이 척수 N-methyl-D-aspartate receptor (NMDAR)의 NR-2B subunit의 발현 및 인산화에 미치는 영향을 조사하였다. 방법 : Sprague-Dawley계 흰쥐를 Storkson등의 방법에 의해 척수막의 지주막하강에 catheter를 삽입하는 수술을 행한 후 마비등의 척수 손상을 나타내지 않는 개체를 대상으로 하였다. N-methyl-D-aspartate (NMDA) antagonist인 D-2-amino-5- phosphonopentanoic acid (AP-5)를 투여한 후 족삼리와 삼음교에 해당하는 부위에 30분간 전침 자극하였다. 무통각 여부는 hot plate test를 시행하였으며 NMDAR NR-2 subunit 발현과 인산화 여부는 Western blot과 면역조직화학적으로 살펴보았다. 결과 : 전침 무통각은 전침 자극 후 180분 후까지 지속되었으며 NMDA antagonist인 AP-5를 투여하였을 때 전침 무통각이 저하되었으나 유의성은 나타내지 않았다. Western blot 분석으로 보아 NMDAR NR-2B 및 인산화 NR-2B의 발현은 전침자극에 의해 미약한 증가를 보이나 AP-5투여에 의해 현저한 저해를 보였다. 면역조직화학에 의한 척수배각 구역별 발현을 보면 NMDAR NR-2B 및 인산화 NR-2B는 전 배각에 걸쳐 관찰되나 경부(층판 V-VI)에서 약한 반응을 보였다. 전침 자극에 의한 각 군별 NR-2B 발현은 유의한 차이를 보여 주지 않았으나 인산화 NR-2B는 천층(층판I-II) 및 고유핵 층판(III-IV)에서 유의성 있는 증가를 보였다. 전침 자극시 AP-5 투여는 유의성은 보이지 않았으나 인산화 NR-2B 발현을 저해하였다. 결론: 저주파 2Hz 전침에 의한 무통각은 NMDA antagonist인 AP-5 투여에 의해 저해될 뿐 아니라 NMDAR NR-2B subunit의 인산화를 저해하는 것으로 보아 전침 무통각의 과정에 NMDAR 및 NMDAR NR-2B의 인산화가 관여함을 알 수 있다.

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The activation of NLRP3 inflammasome potentiates the immunomodulatory abilities of mesenchymal stem cells in a murine colitis model

  • Ahn, Ji-Su;Seo, Yoojin;Oh, Su-Jeong;Yang, Ji Won;Shin, Ye Young;Lee, Byung-Chul;Kang, Kyung-Sun;Sung, Eui-Suk;Lee, Byung-Joo;Mohammadpour, Hemn;Hur, Jin;Shin, Tae-Hoon;Kim, Hyung-Sik
    • BMB Reports
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    • v.53 no.6
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    • pp.329-334
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    • 2020
  • Inflammasomes are cytosolic, multiprotein complexes that act at the frontline of the immune responses by recognizing pathogen- or danger-associated molecular patterns or abnormal host molecules. Mesenchymal stem cells (MSCs) have been reported to possess multipotency to differentiate into various cell types and immunoregulatory effects. In this study, we investigated the expression and functional regulation of NLR Family Pyrin Domain Containing 3 (NLRP3) inflammasome in human umbilical cord blood-derived MSCs (hUCB-MSCs). hUCB-MSCs expressed inflammasome components that are necessary for its complex assembly. Interestingly, NLRP3 inflammasome activation suppressed the differentiation of hUCB-MSCs into osteoblasts, which was restored when the expression of adaptor proteins for inflammasome assembly was inhibited. Moreover, the suppressive effects of MSCs on T cell responses and the macrophage activation were augmented in response to NLRP3 activation. In vivo studies using colitic mice revealed that the protective abilities of hUCB-MSCs increased after NLRP3 stimulation. In conclusion, our findings suggest that the NLRP3 inflammasome components are expressed in hUCB-MSCs and its activation can regulate the differentiation capability and the immunomodulatory effects of hUCB-MSCs.

Craniospinal Neurenteric Cysts: Various MR Imaging Features (뇌척수 신경장관 낭종: 다양한 자기공명영상소견)

  • Jeon, Se-Jeong;Sohn, Chul-Ho;Kim, Eun-Hee;Son, Kyu-Ri;Park, Sung-Hye;Chang, Kee-Hyun
    • Investigative Magnetic Resonance Imaging
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    • v.13 no.1
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    • pp.54-62
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    • 2009
  • Purpose : Craniospinal neurenteric (NE) cysts are rare developmental non-neoplastic cysts of the central nervous system with diverse MR imaging findings. The purpose of this study was to evaluate various MR imaging findings of intracranial and intraspinal NE cysts. Materials and Methods : We retrospectively reviewed the MR imaging findings of six NE cysts that were confirmed by pathology. We evaluated anatomic location, signal intensity, size and enhancement pattern of NE cysts. Results : Two intracranial lesions were located extra-axially in the cerebellopontine angle and quadrigeminal cisterns. Three spinal lesions were intraduralextramedullary cysts, located ventral to the spinal cord, but one thoracic lesion was an intramedullary cyst. The signal intensity of the cysts was hyperintense on T1-weighted images as compared with the cerebrospinal fluid (CSF) for two intracranial lesions and one cervical lesion. In addition, all intracranial lesions showed diffusion restriction. For the remaining three spinal lesions, the signal intensity was nearly the same as the signal intensity of the CSF as seen on both T1- and T2-weighted images. On contrast-enhanced studies, two intracranial cysts showed a small nodular enhancement and one thoracic spinal lesion showed rim enhancement. Conclusion : NE cysts have various locations, signal intensities, and possible focal nodular or rim enhancement. Therefore, NE cysts can be included in the differential diagnosis of various craniospinal cystic or tumorous cystic lesions.

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An Image Management System of Frame Unit on a Hand-held Device Environments (휴대장치 환경을 위한 프레임 단위의 영상 데이터 관리 시스템)

  • Choi, Jun-Hyeog;Yoon, Kyung-Bae;Han, Seung-Jin
    • Journal of the Korea Society of Computer and Information
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    • v.13 no.7
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    • pp.29-36
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    • 2008
  • This paper proposes algorithm for the system that can search for an image of a frame unit, and we implement it. A system already inserts in images after generating the cord that mechanical decoding and identification are possible. We are independent of an external noise in a frame unit, and a system to propose at these papers can search for an image recorded by search condition to include recording date, recording time, a recording place or filming course etc. This system is composed by image insertion wealth to insert data to an image to data image code generation wealth, a frame generating data image code you apply a code generation rule to be fixed in order to express to a price to have continued like data entry wealth, GPS locator values and direction price receiving an image signal, image decoding signals and an image search signal to include search condition, and to have continuity from users each of an image. Also, image decoding we decipher about the noise that was already added from the outsides in a telerecording process, a copy process or storage processes inserted in images by real time, and searching image information by search condition. Consequently we implement decoder, and provide the early system that you use, and we easily insert data code among images. and we can search. and maximization can get precision regarding an image search and use satisfaction as we use algorithm to propose at these papers.

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