• Title/Summary/Keyword: human tissue modeling

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Characterization of a Myostatin-like Gene from the Scallop Patinopecten yessoensis

  • Kim, Hyun-Woo;Kim, Hak-Jun;Yoo, Myong-Suk
    • Fisheries and Aquatic Sciences
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    • v.10 no.1
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    • pp.16-23
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    • 2007
  • Myostatin (GDF8) is a growth factor that limits muscle tissue growth and development in vertebrates. We isolated a myostatin-like gene (Py-MSTN) from the marine invertebrate, the scallop Patinopecten yessoensis. Py-MSTN was highly expressed in the adductor muscle and in the gill unexpectedly. Amino acid analysis showed that Py-MSTN has 49% amino acid sequence identity and 64% similarity to human myostatin (Hs-MSTN), and 42% identity and 61% similarity to myoglianin, the only invertebrate homolog. These results indicated that Py-MSTN may be functionally similar to the vertebrate MSTN than the invertebrate homolog. Phylogenetic analysis suggested that Py-MSTN is an ancestral form of vertebrate MSTN and GDF11 and does not belong to other $TGF-{\beta}$ family members. Molecular modeling showed that Py-MSTN exhibits a similar tertiary structure to mammalian BMP7, a member of $TGF-{\beta}$ family. In addition, the amino acid residues which contact extracellular domain of the receptor were relavively conserved. Given these results, we propose that Py-MSTN is a functionally active member of the $TGF-{\beta}$ family and is involved In muscle growth and regulation.

A Novel Suberoylanilide Hydroxamic Acid Histone Deacetylase Inhibitor Derivative, N25, Exhibiting Improved Antitumor Activity in both Human U251 and H460 Cells

  • Zhang, Song;Huang, Wei-Bin;Wu, Li;Wang, Lai-You;Ye, Lian-Bao;Feng, Bing-Hong
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.10
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    • pp.4331-4338
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    • 2014
  • $N^1$-(2, 5-dimethoxyphenyl)-$N^8$-hydroxyoctanediamide (N25) is a novel SAHA cap derivative of HDACi, with a patent (No. CN 103159646). This invention is a hydroxamic acid compound with a structural formula of $RNHCO(CH_2)6CONHOH$ (wherein R=2, 5dimethoxyaniline), a pharmaceutically acceptable salt which is soluble. In the present study, we investigated the effects of N25 with regard to drug distribution and molecular docking, and anti-proliferation, apoptosis, cell cycling, and $LD_{50}$. First, we designed a molecular approach for modeling selected SAHA derivatives based on available structural information regarding human HDAC8 in complex with SAHA (PDB code 1T69). N25 was found to be stabilized by direct interaction with the HDAC8. Anti-proliferative activity was observed in human glioma U251, U87, T98G cells and human lung cancer H460, A549, H1299 cells at moderate concentrations ($0.5-30{\mu}M$). Compared with SAHA, N25 displayed an increased antitumor activity in U251 and H460 cells. We further analyzed cell death mechanisms activated by N25 in U251 and H460 cells. N25 significantly increased acetylation of Histone 3 and inhibited HDAC4. On RT-PCR analysis, N25 increased the mRNA levels of p21, however, decreased the levels of p53. These resulted in promotion of apoptosis, inducing G0/G1 arrest in U251 cells and G2/M arrest in H460 cells in a time-dependent and dose-dependent manner. In addition, N25 was able to distribute to brain tissue through the blood-brain barrier of mice ($LD_{50}$: 240.840mg/kg). In conclusion, our findings demonstrate that N25 will provide an invaluable tool to investigate the molecular mechanism with potential chemotherapeutic value in several malignancies, especially human glioma.

A Biomechanical Modeling of Human Pharyngeal Muscular Dysfunction by Using FEM(Finite Element Method) (유한요소법을 이용한 인두의 기능이상에 대한 생체역학적 모델)

  • Kim Sung Jae;Bae Ha Suk;Choi Byeong Cheol;Kim Sung Min
    • Journal of Biomedical Engineering Research
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    • v.24 no.6 s.81
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    • pp.515-522
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    • 2003
  • Pharynx is a system transporting foods by peristaltic motion(contraction and expansion movement! into the esophagus and functioning as airway passages. In this study, structural changes of pharyngeal dysfunction are analyzed by biomechanical model using CT and FEM(finite clement method). Loading condition was assumed that equal pressure was loaded sequentially to inside of pharyngeal tissue. In order to analyze the pharyngeal muscular dysfunction by biomechanical model. the pharyngeal dysfunctions was classified into 3 cases. Taking into account the clinical complication by neuromuscular symptoms such as pharyngeal dysfunction after stroke. we assumed that a change of material property is caused by muscular tissue stiffness. A deformation of cross sectional area of the pharynx is analyzed increasing the stiffness $25\%,\;50\%,\;75\%$ in each case on the basis of stress-strain relationship. Based on three-dimensional reconstruction of pharyngeal structure using limited factor - techniques and the optimization procedure by means of inverse dynamic approach. the biomechanical model of the human pharynx is implemented. The results may be used as clinical index illustrating the degree of pharyngeal muscular dysfunction. This study may be used as useful diagnostic model in discovering early deglutitory impediment caused by physiological or pathological pharyngeal dysfunction.

Mechanical Behavior of the Soleus Aponeuroses during Voluntary Contraction Using Magnetic Resonance Imaging Technique (자기공명 영상기법을 이용한 인체 가자미근 건막의 기계학적 특성 연구)

  • Lee, Hae-Dong
    • Korean Journal of Applied Biomechanics
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    • v.17 no.1
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    • pp.121-127
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    • 2007
  • Muscle force produced by muscle fibers is transmitted to bones via tendinous structures(aponeuroses and tendon), resulting in joint(s) movement. As force-transmitting elements, mechanical behavior of aponeuroses and tendon are closely related with the function of muscle-tendon complex. The purpose of this study was to determine strain characteristics of aponeuroses for in-vivo human soleus muscle during submaximal voluntary contractions using an advanced medical imaging technique, velocity-encoded phase-contrast magnetic resonance imaging (VE-PC MRI). VE-PC MRI of the soleus muscle-tendon complex was acquired during submaximal isometric plantarflexion contraction-relaxation cycle (n = 7), using 3.0T Trio MRI scanner(Siemens AG, Malvern, MA). From the VE-PC MRI containing the tissue velocity in superior-inferior direction, twenty regions of interest(20 ROI; 10 on the anterior aponeurosis and 10 on the posterior aponeurosis) were tracked. During the isometric plantarflexion contraction-relaxation cycle, velocity and displacement profiles were different between the anterior and posterior aponeuroses, indicating heterogeneous strain behavior along the length of the leg. The anterior aponeurosis elongated while the posterior aponeurosis shortened during the initial phase of the contraction. Moreover, strain behavior of the posterior aponeurosis was different from that of the Achilles tendon. Possible explanation for the observed variations in strain behavior of aponeuroses was investigated with morphological assessment of the soleus muscle and it was found that the intramuscular tendinous structures significantly vary among subjects. In conclusion, the heterogeneous mechanical behavior of the soleus aponeuroses and the Achilles tendon suggests that the complexity of skeletal muscle-tendon complex should be taken into consideration when modeling the complex for better understanding of its functions.

Radiation Therapy Using M3 Wax Bolus in Patients with Malignant Scalp Tumors (악성 두피 종양(Scalp) 환자의 M3 Wax Bolus를 이용한 방사선치료)

  • Kwon, Da Eun;Hwang, Ji Hye;Park, In Seo;Yang, Jun Cheol;Kim, Su Jin;You, Ah Young;Won, Young Jinn;Kwon, Kyung Tae
    • The Journal of Korean Society for Radiation Therapy
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    • v.31 no.1
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    • pp.75-81
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    • 2019
  • Purpose: Helmet type bolus for 3D printer is being manufactured because of the disadvantages of Bolus materials when photon beam is used for the treatment of scalp malignancy. However, PLA, which is a used material, has a higher density than a tissue equivalent material and inconveniences occur when the patient wears PLA. In this study, we try to treat malignant scalp tumors by using M3 wax helmet with 3D printer. Methods and materials: For the modeling of the helmet type M3 wax, the head phantom was photographed by CT, which was acquired with a DICOM file. The part for helmet on the scalp was made with Helmet contour. The M3 Wax helmet was made by dissolving paraffin wax, mixing magnesium oxide and calcium carbonate, solidifying it in a PLA 3D helmet, and then eliminated PLA 3D Helmet of the surface. The treatment plan was based on Intensity-Modulated Radiation Therapy (IMRT) of 10 Portals, and the therapeutic dose was 200 cGy, using Analytical Anisotropic Algorithm (AAA) of Eclipse. Then, the dose was verified by using EBT3 film and Mosfet (Metal Oxide Semiconductor Field Effect Transistor: USA), and the IMRT plan was measured 3 times in 3 parts by reproducing the phantom of the head human model under the same condition with the CT simulation room. Results: The Hounsfield unit (HU) of the bolus measured by CT was $52{\pm}37.1$. The dose of TPS was 186.6 cGy, 193.2 cGy and 190.6 cGy at the M3 Wax bolus measurement points of A, B and C, and the dose measured three times at Mostet was $179.66{\pm}2.62cGy$, $184.33{\pm}1.24cGy$ and $195.33{\pm}1.69cGy$. And the error rates were -3.71 %, -4.59 %, and 2.48 %. The dose measured with EBT3 film was $182.00{\pm}1.63cGy$, $193.66{\pm}2.05cGy$ and $196{\pm}2.16cGy$. The error rates were -2.46 %, 0.23 % and 2.83 %. Conclusions: The thickness of the M3 wax bolus was 2 cm, which could help the treatment plan to be established by easily lowering the dose of the brain part. The maximum error rate of the scalp surface dose was measured within 5 % and generally within 3 %, even in the A, B, C measurements of dosimeters of EBT3 film and Mosfet in the treatment dose verification. The making period of M3 wax bolus is shorter, cheaper than that of 3D printer, can be reused and is very useful for the treatment of scalp malignancies as human tissue equivalent material. Therefore, we think that the use of casting type M3 wax bolus, which will complement the making period and cost of high capacity Bolus and Compensator in 3D printer, will increase later.

Comparison of Algorithms for Generating Parametric Image of Cerebral Blood Flow Using ${H_2}^{15}O$ PET Positron Emission Tomography (${H_2}^{15}O$ PET을 이용한 뇌혈류 파라메트릭 영상 구성을 위한 알고리즘 비교)

  • Lee, Jae-Sung;Lee, Dong-Soo;Park, Kwang-Suk;Chung, June-Key;Lee, Myung-Chul
    • The Korean Journal of Nuclear Medicine
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    • v.37 no.5
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    • pp.288-300
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    • 2003
  • Purpose: To obtain regional blood flow and tissue-blood partition coefficient with time-activity curves from ${H_2}^{15}O$ PET, fitting of some parameters in the Kety model is conventionally accomplished by nonlinear least squares (NLS) analysis. However, NLS requires considerable compuation time then is impractical for pixel-by-pixel analysis to generate parametric images of these parameters. In this study, we investigated several fast parameter estimation methods for the parametric image generation and compared their statistical reliability and computational efficiency. Materials and Methods: These methods included linear least squres (LLS), linear weighted least squares (LWLS), linear generalized least squares (GLS), linear generalized weighted least squares (GWLS), weighted Integration (WI), and model-based clustering method (CAKS). ${H_2}^{15}O$ dynamic brain PET with Poisson noise component was simulated using numerical Zubal brain phantom. Error and bias in the estimation of rCBF and partition coefficient, and computation time in various noise environments was estimated and compared. In audition, parametric images from ${H_2}^{15}O$ dynamic brain PET data peformed on 16 healthy volunteers under various physiological conditions was compared to examine the utility of these methods for real human data. Results: These fast algorithms produced parametric images with similar image qualify and statistical reliability. When CAKS and LLS methods were used combinedly, computation time was significantly reduced and less than 30 seconds for $128{\times}128{\times}46$ images on Pentium III processor. Conclusion: Parametric images of rCBF and partition coefficient with good statistical properties can be generated with short computation time which is acceptable in clinical situation.