• Title/Summary/Keyword: Helical

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Structural Study of the Cytosolic C-terminus of Vanilloid Receptor 1

  • Seo, Min-Duk;Won, Hyung-Sik;Oh, Uh-Taek;Lee, Bong-Jin
    • Journal of the Korean Magnetic Resonance Society
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    • v.11 no.2
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    • pp.85-94
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    • 2007
  • Vanilloid receptor I [transient receptor potential vanilloid subfamily member 1 (TRPV1), also known as VR1] is a non-selective cationic channel activated by noxious heat, vanilloids, and acid, thereby causing pain. VR1 possesses six transmembrane domain and N-and C-terminus cytosolic domains, and appears to be a homotetramer. We studied the structural properties of Cterminus of VR1 (VR1C) using CD and NMR spectroscopy. DPC micelles, with a zwitterionic surface, and SDS micelles, with a negatively charged surface, were used as a membrane mimetic model system. Both SDS and DPC micelles could increase the stability of helical structures and/or reduce the aggregation form of the VR1C. However, the structural changing mode of the VR1C induced by the SDS and DPC micelles was different. The changes according to the various pHs were also different in two micelles conditions. Because the net charges of the SDS and DPC micelles are negative and neutral, respectively, we anticipate that this difference might affect the structure of the VR1C by electrostatic interaction between the surface of the VR1C and phospholipids of the detergent micelles. Based on these similarity and dissimilarity of changing aspects of the VR1C, it is supposed that the VR1C probably has the real pI value near the pH 7. Generally, mild extracellular acidic pH ($6.5{\sim}6.8$) potentiates VRI channel activation by noxious heat and vanilloids, whereas acidic conditions directly activate the channel. The channel activation of the VRI might be related to the structural change of VR1C caused by pH (electrostatic interactions), especially near the pH 7. By measuring the $^1-^{15}N$ TROSY spectra of the VR1C, we could get more resolved and dispersed spectra at the low pH and/or detergent micelles conditions. We will try to do further NMR experiments in low pH with micelles conditions in order to get more information about the structure of VR1C.

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Effects of $H^{+}$ on the Contraction Induced by Various Agonists in the Renal Artery of a Rabbit (수소이온농도 변화의 수축물질에 따른 가토신동맥 수축에 미치는 영향과 기전)

  • Chang, Seok-Jong;Kim, Se-Hoon;Jeon, Byeong-Hwa;Park, Hae-Kun
    • The Korean Journal of Physiology
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    • v.24 no.1
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    • pp.161-170
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    • 1990
  • The effects of $H^{+}$ on the arterial contraction and their mechanisms were investigated in the renal artery of a rabbit. The helical strips of isolated renal artery were immersed in the HEPES-buffered or $CO_{2}/HCO_{3}^{-}$-buffered Tyrode's solution. The contractions induced by agonists (norepinephrine, histamine, serotonin and angiotensin II) or high $K^{+}$ were observed with change of extracellular or intracellular $H^{+}$ concentration. The contractions induced by norepinephrine, histamine, serotonin, angiotensin II or high $K^{+}$ in HEPES-buffered Tyrode's solution were inhibited by increase in extracellular $H^{+}$ concentration and potentiated by decrease in extracellular $H^{+}$ concentration. The degrees of these effects were most evident in the contraction induced by serotonin and angiotensin II, moderate in those by histamine and high $K^{+}$, and least in those by norepinephrine. Maximal contraction by norepinephrine, histamine and high $K^{+}$ were not influenced by change in extracellular $H^{+}$ concentration, but influenced in those contration by serotonin and angiotensin II. The attenuated contractions by an acidic pH were not returned to the level of contraction at normal pH (7.4) by elevation of extracellular $Ca{2+}$ concentration. The agonists (norepinephrine, histamine and serotonin)-induced contractions in $Ca{2+}$-free Tyrode's solution were also attenuated by increase in extracellular $H^{+}$ concentration and potentiated by decrease in extracellular $H^{+}$ concentration. Elevation of $Pco_{2}$ in the $CO_{2}/HCO_{3}^{-}$-buffered Tyrode's solution, which increase the intracellular $H^{+}$ concentration, at constant extracellular pH (7.4), increased the contraction by 30 mM $K^{+}$. From the above results, it is suggested that the decrease in contractions by increase in extracellular $H^{+}$ concentration may be resulted from that $H^{+}$ make the receptors less sensitive to agonists and cell membrane hyperpolarize and then inhibit the $Ca{2+}$ influx as well as $Ca{2+}$ release from intracellular $Ca{2+}$ storage site.

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Contractile Mechanisms of Serotonin in the Renal Arterial smooth muscle of a Rabbit (Serotonin에 의한 가토 신동맥 평활근 수축기전)

  • Lee, Woo-Young;Kim, Se-Hoon;Chang, Seok-Jong
    • The Korean Journal of Physiology
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    • v.24 no.1
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    • pp.67-76
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    • 1990
  • The contractile mechanisms of serotonin were investigated in the renal artery of a rabbit. The helical strips of isolated renal artery were immersed in the normal or $Ca^{2+}$-free tris-buffered Tyrode's solution, which was equilibrated with 100% $O_{2}$ at $35^{\circ}C$. The contraction by serotonin or norepinephrine (NE) began at $1{\times}10^{-7}\;M$ and reached the maximal contraction at $1{\times}10^{-5}\;M$. The maximal contraction by serotonin corresponded to $58.1{\pm}4.2%$ of maximal contraction by NE. Cyproheptadine, a serotonin receptor blocker, shifted the concentration-response curve to the right without any reduction in the maximum response but shifted that of NE to the right with reduction in maximum response. And phentolamine, an ${\alpha}-receptor$ blocker, shifted the concentration-response curve of serotonin or NE without any reduction in maximum responses. The $pA_{2}$ values for cyproheptadine against serotonin and NE were $10.35{\pm}0.04$ and $8.45{\pm}0.13$, respectively. The $pA_{2}$ values for phentolamine against serotonin and NE were $6.87{\pm}0.04$ and $8.14{\pm}0.08$, respectively. after the pretreatment with 6-hydroxydopamine, the contraction induced by 100 mM $K^{+}$, tyramine and serotonin reduced to $83.0{\pm}2.0$, $26.8{\pm}6.2$ and $82.0{\pm}3.5%$ of control, respectively. The contraction by serotonin in the $Ca^{2+}$-free Tyrode's solution was increased and sustained with the addition of $Ca^{2+}$ extracellulary. The serotonin-sensitive intracellular $Ca^{2+}$ pool was depleted completely by the pretreatment with NE, but the NE-sensitive intracellular $Ca^{2+}$ pool was depleted partially by the pretreatment with serotonin. From the above results, it is suggested that the contraction induced by serotonin in the renal artery of a rabbit may be due to mechanisms in which serotonin acts directly on specific serotonin receptors and also acts indirectly on ${\alpha}-adrenoceptors$ by displacing NE from neuronal stores.

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The Effects of Prostaglandin $F_{2{\alpha}}$ on the Contractility of Vascular Smooth Muscle in the Aortic Strip of Rabbits (Prostaglandin $F_{2{\alpha}}$가 가토 대동맥 평활근 수축성에 미치는 영향)

  • Chung, Soo-Sung;Kim, Se-Hoon;Chang, Seok-Jong;Park, Hae-Kun
    • The Korean Journal of Physiology
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    • v.23 no.1
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    • pp.99-108
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    • 1989
  • The effects of prostaglandin $(PGF_{2{\alpha}})$ on the contractility of vascular smooth muscle were investigated in the helical strip of the rabbit aorta. The aortic strip was immersed in the phosphate-buffered Tyrode's solution which was equilibrated with 100% $O_{2}$ at $35^{\circ}C$ and its isometric tension was measured. The contraction was induced by $(PGF_{2{\alpha}})$, norepinephrine (NE), or potassium (40 mM) in the nomal Tyrode's solution (1 mM, $Ca^{2+}$) or $Ca^{2+}-free$ Tyrode's solution. Effects of verapamil and phentolamine on the contraction were also observed. The aortic strip began to contract at the concentration of $5\;{\mu}g%$ and reached the maximal contraction at the concentration of $150\;{\mu}g%$ $(PGF_{2{\alpha}})$. The maximal contraction was corresponded respectively to $52.2{\pm}3.0%$ and $81.5{\pm}3.5%$ of maximal contraction by NE $(1{\times}10^{-5}M)$ and 40 mM $K^{+}$. And the maximal contractions by $(PGF_{2{\alpha}})$ or NE were induced at the concentration of about 1 mM $Ca^{2+}$. $(PGF_{2{\alpha}})$ induced the contraction of aortic strip even after induction of contraction by 40 mM $K^{+}$ and the contraction by $(PGF_{2{\alpha}})$ was not blocked by the ${\alpha}-receptor$ blocker, phentolamine. And the contraction by the $(PGF_{2{\alpha}})$ was inhibited partially by a verapamil at the concentration of $1{\times}10^{-5}M$ and the contraction began to increase at the concentration of $1{\times}10^{-4}M$ verapamil. Whereas the contraction by NE was completely blocked by verapamil. Though both the $(PGF_{2{\alpha}})$ and NE induced the contraction in the $Ca^{2+}-free$ Tyrode's solution, the peak tension was not maintained. But the rate of tension decline was lower in the contraction by $(PGF_{2{\alpha}})$ than in that by NE. The verapamil did not inhibit the contraction by $(PGF_{2{\alpha}})$ in the $Ca^{2+}-free$ Tyrode's solution and increased the contraction at the concentration of above $1{\times}10^{-4}M$. The NE-induced contraction in the $Ca^{2+}-free$ Tyrode's solution was inhibited completely by a verapamil. From the above results it is suggested that the contraction induced by $(PGF_{2{\alpha}})$ results from the promotion of the both $Ca^{2+}$ influx and the intracellular $Ca^{2+}$ release by different way from NE.

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Dosimetric evaluation of Tomotherapy and four-box field conformal radiotherapy in locally advanced rectal cancer

  • Yu, Mina;Jang, Hong Seok;Jeon, Dong Min;Cheon, Geum Seong;Lee, Hyo Chun;Chung, Mi Joo;Kim, Sung Hwan;Lee, Jong Hoon
    • Radiation Oncology Journal
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    • v.31 no.4
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    • pp.252-259
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    • 2013
  • Purpose: To report the results of dosimetric comparison between intensity-modulated radiotherapy (IMRT) using Tomotherapy and four-box field conformal radiotherapy (CRT) for pelvic irradiation of locally advanced rectal cancer. Materials and Methods: Twelve patients with locally advanced rectal cancer who received a short course preoperative chemoradiotherapy (25 Gy in 5 fractions) on the pelvis using Tomotherapy, between July 2010 and December 2010, were selected. Using their simulation computed tomography scans, Tomotherapy and four-box field CRT plans with the same dose schedule were evaluated, and dosimetric parameters of the two plans were compared. For the comparison of target coverage, we analyzed the mean dose, $V_{nGy}$, $D_{min}$, $D_{max}$, radical dose homogeneity index (rDHI), and radiation conformity index (RCI). For the comparison of organs at risk (OAR), we analyzed the mean dose. Results: Tomotherapy showed a significantly higher mean target dose than four-box field CRT (p = 0.001). But, $V_{26.25Gy}$ and $V_{27.5Gy}$ were not significantly different between the two modalities. Tomotherapy showed higher $D_{max}$ and lower $D_{min}$. The Tomotherapy plan had a lower rDHI than four-box field CRT (p = 0.000). Tomotherapy showed better RCI than four-box field CRT (p = 0.007). For OAR, the mean irradiated dose was significantly lower in Tomotherapy than four-box field CRT. Conclusion: In locally advanced rectal cancer, Tomotherapy delivers a higher conformal radiation dose to the target and reduces the irradiated dose to OAR than four-box field CRT.

Preliminary results of entire pleural intensity-modulated radiotherapy in a neoadjuvant setting for resectable malignant mesothelioma

  • Hong, Ji Hyun;Lee, Hyo Chun;Choi, Kyu Hye;Moon, Seok Whan;Kim, Kyung Soo;Hong, Suk Hee;Hong, Ju-Young;Kim, Yeon-Sil;Multidisciplinary Team of Lung Cancer in Seoul St. Mary's Hospital
    • Radiation Oncology Journal
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    • v.37 no.2
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    • pp.101-109
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    • 2019
  • Purpose: The purpose of this study is to evaluate the safety and efficacy of the multimodality treatment with neoadjuvant intensity-modulated radiotherapy (IMRT) for resectable clinical T1-3N0-1M0 malignant pleural mesothelioma (MPM). Materials and Methods: A total of eleven patients who received neoadjuvant chemotherapy and radiotherapy between March 2016 and June 2018 were reviewed. Patients received 25 Gy in 5 fractions to entire ipsilateral hemithorax with helical tomotherapy. Results: All of patients were men with a median age of 56 years. Epithelioid subtype was found in 10 patients. All patients received neoadjuvant chemotherapy with pemetrexed-cisplatin regimen. Ten patients (90.9%) completed 25 Gy/5 fractions and one (9.0%) completed 20 Gy/4 fractions of radiotherapy. IMRT was well tolerated with only one acute grade 3 radiation pneumonitis. Surgery was performed 1 week (median, 8 days; range, 1 to 15 days) after completing IMRT. Extrapleural pneumonectomy was performed in 4 patients (36.3%), extended pleurectomy/decortication in 2 (18.2%) and pleurectomy/decortications in 5 (63.6%). There was no grade 3+ surgical complication except two deaths after EPP in 1 month. Based on operative findings and pathologic staging, adjuvant chemotherapy was delivered in 7 patients (63.6%), and 2 (18.2%) were decided to add adjuvant radiotherapy. After a median follow-up of 14.6 months (range, 2.8 to 30 months), there were 3 local recurrence (33.3%) and 1 distant metastasis (11.1%). Conclusion: Neoadjuvant entire pleural IMRT can be delivered with a favorable radiation complication. An optimal strategy has to be made in resectable MPM patients who would benefit from neoadjuvant radiation and surgery. Further studies are needed to look at long-term outcomes.

Effect of cutting flute length and shape on insertion and removal torque of orthodontic mini-implants (교점용 미니 임플랜트의 cutting flute의 길이 및 형태에 따른 식립 및 제거 토크의 비교)

  • Yun, Soon-Dong;Lim, Sung-Hoon
    • The korean journal of orthodontics
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    • v.39 no.2
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    • pp.95-104
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    • 2009
  • Objective: The purpose of this study was to evaluate the effect of length and shape of cutting flute on mechanical properties of orthodontic mini-implants. Methods: Three types of mini-implants with different flute patterns (Type A with 2.6 mm long flute, Type B with 3.9 mm long and straight flute, Type C with 3.9 mm long and helical flute) were inserted into the biomechanical test blocks (Sawbones Inc., USA) with 2 mm and 4 mm cortical bone thicknesses to test insertion and removal torque. Results: In 4 mm cortical bone thickness, Type C mini-implants showed highest maximum insertion torque, then Type A and Type B in order. Type C also showed shortest total insertion time and highest maximum removal torque, but Type A and B didn't showed statistically significant difference in insertion time and removal torque. In 2 mm cortical bone thickness, there were no significant difference in total insertion time and maximum removal torque in three types of mini-implants, but maximum insertion torque of Type A was higher than two other Types of mini-implants. Conclusions: Consideration about length and shape of cutting flute of mini-implant is also required when the placement site has thick cortical bone.

Analogues of Hybrid Antimicrobial Peptide, CAMA-P2, Designed with Improved Antimicrobial and Synergistic Activities

  • Jeong, Ki-Woong;Shin, So-Young;Kim, Jin-Kyoung;Kim, Yang-Mee
    • Bulletin of the Korean Chemical Society
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    • v.32 no.8
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    • pp.2577-2583
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    • 2011
  • We have designed a 20-residue hybrid peptide CA(1-8)-MA(1-12) (CAMA) incorporating residues 1-8 of cecropin A (CA) and residues 1-12 of magainin 2 (MA) with high bacterial cell selectivity. CAMA-P2 is an ${\alpha}$-helical antimicrobial peptide designed from a CAMA hybrid peptide and substitution of Gly-Ile-Gly hinge sequence of CAMA to Pro influences the flexibility at central part of CAMA. Based on structure-activity relationships of CAMA peptides, to investigate the effects of the total positive charges on antimicrobial activity of CAMA-P2, the $Ser^{14}{\rightarrow}$Lys analogue (CAMA-syn1) was synthesized. The role of tryptophan at C-terminal ${\alpha}$-helix on its antimicrobial activity as well as synergistic activity was also investigated using $Ser^{14}{\rightarrow}$Lys/$Phe^{18}{\rightarrow}$Trp analogue (CAMA-syn2). Also, we designed CAMA-syn3 by substitution of $Lys^{16}$ located opposite side of substituted $Lys^{14}$ of CAMA-syn1 with Leu residue, resulting in increase of hydrophobicity and amphipathicity of the peptide. All of CAMA-syn analogues showed good antimicrobial activities similar to those of CAMA and CAMA-P2. The CAMA-syn1 and CAMA-syn2 showed low hemolytic activity and cytotoxicity against human keratinocyte Haca-T cells while CAMA-syn3 showed hemolytic activity and cytotoxicity at its MIC value. We then investigated their abilities to act synergistically in combination with the antimicrobial flavonoids and synthetic compounds screened in our laboratory. The results showed that all peptides exhibited synergistic effects with dihydrobinetin, while only CAMA-syn2 exhibited synergistic effects with YKAs3001 against both S. aureus and MRSA, suggesting that Trp residue at C-terminus of CAMA-syn2 may facilitate the polar antibiotic flavonoids and synthetic compounds to permeabilize the membrane. This study will be useful for the development of new antibiotic peptides with potent antimicrobial and synergistic activity but without cytotoxicity.

ELECTRON MICROSCOPIC STUDY ON THE RESPONSES OF THE PERIODONTAL TISSUE ON THE TENSION SIDE FOLLOWING EXPERIMENTAL TOOTH MOVEMENT (실험적 치아 이동시 견인측 치주조직에 미치는 영향에 관한 전자현미경적 연구)

  • Chang, Ji Woo
    • The korean journal of orthodontics
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    • v.14 no.1
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    • pp.65-81
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    • 1984
  • In order to observe the responses of the periodontal tissue on the tension side following the experimental tooth movement, 35 Guinea pigs were divided into the control group (5 animals) and 6 experimental groups (3 movement groups and 3 retention groups) consisting of each 5 animals. The experimental tooth movement of Guinea pig's upper incisors installing open helical loop were carried out by rendering continuous force : 5g (1st groups) 35g (2nd groups), 100g (3rd groups), respectively for 7 days. 3 movement groups (15 animals) were sacrificed soon after the continuous force, and 3 retention groups (15 animals) were sacrificed after the retention period of another 7 days. The following results were obtained from the observation of the surrounding tissues of teeth on the tension side through light microscopy any transmission electron microscopy. 1. The vessel walls in the experimental groups were thinner than those of the control group, the number of blood vessel had the tendency to increase. The greater the strong force applied to each group, the more the destruction of cells and fibers was found and the more the number of the red blood cell of vessel outside appeared. 2. New collagen fibers were produced from fibroblasts in the 1st groups (light force), but were produced rather less in the 2nd groups (medium force) and the 3rd groups (heavy force). 3. In the forming patterns of the new alveolar bone of the 3rd groups (heavy force), the bone trabeculae were formed towards the direction of the force to be applied, but the new alveolar bone in the 1st groups (light force) was produced evenly throughout the all surfaces of the alveolar bone rather than the patterns of bone trabeculae ; therefore, the patterns of new alveolar bone were observed differently according to the magnitude of the force applied. 4. In the retention group, it was observed that the collagen fibers were produced from the osteoblasts in the marginal areas of the periodontal ligaments being widely opened and were deposited on the alveolar bone surface but the production of collagen fibers from the osteoblasts in the other area of the periodontal ligaments was almost ceased, and a rest line on the new alveolar bone surface was found.

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Comparison of Radiation Doses between 64-slice Single Source and 128-slice Dual Source CT Coronary Angiography in patient (64-slice single source CT와 128-slice dual source CT를 이용한 관상동맥 조영 검사 시 환자선량 비교)

  • Kang, Yeong-Han
    • Journal of the Korean Society of Radiology
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    • v.6 no.2
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    • pp.129-136
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    • 2012
  • The purpose of this study was to estimate radiation doses from 64-slice single source Computed Tomography(SSCT) coronary angiography(CA) and 128-slice dual source Computed Tomography(DSCT). With SSCT CA, the effective dose averaged approximately 13.86 mSv when two dose modulation was not. The mean effective dose for DSCT CA with retrospectively gated helical(RGH) technique was 11.87 mSv, when prospective ECG gating transverse(PGT) without dose modulation technique was 5.61 mSv. The one with dose modulation in PGT technique and flash mode were 3.04 mSv and flash mode was 0.98 mSv respectively. The lifetime attributable risk(LAR) of cancer incidence from SSCT RGH mode averaged approximately 1 for 1,176, and DSCT averaged 1 for 1,960(RGH mode), 1 for 3,030(PGT without modulation), 1 for 5,882(PGT with modulation). Because of CTCA is associated with non-negligible risk of cancer. Doses can be reduced by application PGT, FLASH than RGH using DSCT.