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Gene Expression of Metalloproteinases, Tissue Inhibitors of Metalloproteinases and Cytokines in Adriamycin-induced Cardiomyopathy (아드리아마이신으로 유도된 심근증에서 Metalloproteinase, Metalloproteinase 조직억제자, Cytokine 유전자 발현에 대한 연구)

  • Hong, Young Mi
    • Clinical and Experimental Pediatrics
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    • v.48 no.2
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    • pp.197-203
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    • 2005
  • Purpose : Changes in metalloproteinases(MMP) activity have been demonstrated in several disease states, including rheumatoid arthritis and tumor metastasis. More importantly, increased myocardial MMP activity has been reported to occur in both clinical and experimental forms of dilated cardiomyopathy. There was no report about MMP in adriamycin(ADR)-induced cardiomyopathy. The purpose of this study was to investigate gene expression of MMP and tissue inhibitor of metalloproteinases(TIMP) in ADR-induced cardiomyopathy and clarify the relationship between MMP and cytokines. Methods : Male Sprague-Dawley rats were divided into two groups. The first group was control. The second group was given intraperitoneal injections of ADR(5 mg/kg) twice a week over two weeks. Serum concentrations of MMP, TIMP, interleukin(IL)-6 and tumor necrosis factor(TNF)-${\alpha}$ were measured. RNA extraction was performed from frozen rat hearts. Reverse transcription polymerase chain reaction(RT-PCR) was employed. cDNA Microarray analysis was performed by using a set of 5,184 sequence-verified rat cDNA clones. Results : Serum MMP and TIMP levels were not significantly different between the two groups. IL-6 was $36.8{\pm}2.8pg/mL$ and TNF-${\alpha}$ $2.2{\pm}2.7pg/mL$ in the ADR group. They were significantly higher than in the control group. Serum MMP correlated significantly with TNF-${\alpha}$(r=0.41, P<0.05). There was no gene expression of MMP, IL-6 or TNF-${\alpha}$ in the hearts of both groups. Gene expression of TIMP was significantly depressed in the hearts of the ADR group. Conclusion : These results suggested a potential role for TNF-${\alpha}$ in the regulation of extracellular matrix remodeling in ADR induced cardiomyopathy. Rapid screening of multiple decreased gene expression by DNA chip may be a useful diagnostic test to detect early cardiac injury before developing ADR induced cardiomyopathy.

Incidence and Prognostic Factors of Radiation Pneumonitis in NSCLC Treated with Intensity Modulated Radiation Therapy(IMRT) (세기조절방사선치료(IMRT)로 치료한 비소세포폐암 환자에서의 방사선 폐렴)

  • Kim, Myung-Se
    • Radiation Oncology Journal
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    • v.26 no.1
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    • pp.35-44
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    • 2008
  • Purpose: To evaluate the incidence and prognostic factors of treatment-related pneumonitis in non-small-cell lung cancer(NSCLC) patients treated with intensity modulated radiation therapy(IMRT). Materials and Methods: One-hundred-five patients with NSCLC treated with IMRT between 1 August 2004 and 30 November 2006 were analyzed retrospectively. The mean age of patients was 62.9 years, and squamous carcinomas were confirmed in 81 patients(77%). Sixty-six patients(62.9%) were classified as stage III, and 59 patients had lesions in the right lung. Twenty-seven patients were treated with a dose of 3,060 cGy preoperatively, and 10 patients were given a dose of 5,040 cGy postoperatively. Sixty-eight patients received a dose of 7,020 cGy for curative intent. Sixty-eight patients were treated with the use of the CORVUS planning system and 37 patients were treated with the use of the ECLIPSE planning system. Results: Of 105 patients, 21 patients(20%) had abnormal radiological findings, but only seven patients(6.7%) required treatment for radiation pneumonitis. Six of the seven patients had other serious lesions, including a bronchioesophageal fistula(one patient), recurrence in the treatment field(two patients), brain metastasis(one patient) and lung-to-lung metastasis(two patients); all of these patients died within 19 months after radiation treatment. Sixteen patients(23.5%) that received planning with the CORVUS system had abnormal lung findings. Five patients(13.5%) had abnormal lung findings with the use of the ECLIPSE planning system. Other prognostic factors such as perioperative radiation therapy, a volume over 10% of the V20 volume in the right lung, were also statistically significant. Conclusion: This retrospective analysis suggests that IMRT could be a beneficial treatment modality for the reduction of radiation pneumonitis in NSCLC patients. However, the higher incidence of abnormal radiological findings in perioperative patients treated with relatively lower doses($3,060{\sim}5,040$ cGy) suggest the need for judicious treatment planning in preoperative or postoperative treatment.

Usefulness of Permeability Map by Perfusion MRI of Brain Tumor the Grade Assessment (뇌종양의 등급분류를 위한 관류 자기공명영상을 이용한 투과성영상(Permeability Map)의 유용성 평가)

  • Bae, Sung-Jin;Lee, Joo-Young;Chang, Hyuk-Won
    • Journal of radiological science and technology
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    • v.32 no.3
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    • pp.325-334
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    • 2009
  • Purpose : This study was conducted to assess how effective the permeability ratio and relative cerebral blood volume ratio are to tumor through perfusion MRI by measuring and reflecting the grade assessment and differential diagnosis and the permeability and relative cerebral blood volume of contrast media plunged from blood vessel into organ due to breakdown of blood-brain barrier in cerebral. Subject and Method : Subject of study was 29 patients whose diagnosis were confirmed by biopsy after surgery and 550 (11 slice$\times$50 image) perfusion MRI were used to make image of relative cerebral blood volume with the program furnished on instrument. The other method was to transmit to private computer and the image analysis was made additionally by making image of relative cerebral blood volume-reformulated singular value decomposition, rCBV-rSVD and permeability using IDL.6.2. In addition, Kruskal-wallis test tonggyein non numerical average by a comparative analysis of brain tumors Results : The rCBV ratio (Functool PF; GE Medical Systems and IDL 6.2 program by analysis) and permeability ratio of tumors were as follows; high grade glioma(n=4), (14.75, 19.25) 13.13. low grade astrocytoma(n=5) (14.80, 15.90) 11.60, glioblastoma(n=5) (10.90, 18.60), 22.00, metastasis(n=6) (11.00, 15.08). 22.33. meningioma(n=6) (18.58, 7.67), 5.58. oliogodendroglioma(n=3) (23.33, 16.33, 15.67. Conclusion : It was not easy to classify the grade with the relative cerebral blood volume ratio measured by using the relative cerebral blood image by type of tumors, however, permeability ratio measured by permeability image revealed that the higher the grade of tumor, the higher the measured permeability ratio, showing the assessment of tumor grade is more effective to differential diagnosis.

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Development of a Pre-treating Equipment and the Carcass Disposal System for Infected Poultry (감염가금 전처리 및 폐사가축 처리시스템 개발)

  • Hong, J.T.;Kim, H.J.;Yu, B.K.;Lee, S.H.;Hyun, C.S.;Ryu, I.S.;Oh, K.Y.;Kim, S.;Kwon, J.H.;Tack, D.S.
    • Journal of Animal Environmental Science
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    • v.17 no.2
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    • pp.81-92
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    • 2011
  • When we bury the infected poultry into the ground, we have many problems such as the difficulty of making sufficient area for burying, environmental contamination by the leachate, unpleasant ordor. Also, in case of burning the carcass of the infected poultry, there are some problems such as high cost, dust, unpleasant odor, etc. It could cause environmental contamination which many peoples and environmental organization complains about. In this study, we develop a treating system which treats the infected poultry carcass in a environmental method preventing the environment contamination. This system is composed of many processes. The euthanasia system uses rigid vinyl to trap and to do a euthanasia the infected poultry with lethal gas, carbon dioxide. And then, with the tractor attached grappler infected poultry carcass could be put into the carcass treating system. The euthanasia system uses rigid vinyl to trap the infected birds and to confine lethal gas, carbon dioxide. Infected poultry carcass are moved to carcass disposal system by collecting device which is attached at tractor. The carcass treatment system (capacity of disposal : 6.3 $m^3$) is installed on a truck and do one pass work, which is input, crush, stir, sterilize, and discharge treated carcass. 1,000 chickens was killed within 9.7min by $CO_2$ (300L/min) in the tent (10 $m^3$). The collecting device could carry 142 chickens at a time, and the movable carcass treatment system could sterilize 2 tons carcass per hour (at one time). This treatment systems was eco-friendly because it reduced the volume of carcass by 31.9% with no wastewater generation.

The Optimal Activation State of Dendritic Cells for the Induction of Antitumor Immunity (항종양 면역반응 유도를 위한 수지상세포의 최적 활성화 조건)

  • Nam, Byung-Hyouk;Jo, Wool-Soon;Lee, Ki-Won;Oh, Su-Jung;Kang, Eun-Young;Choi, Yu-Jin;Do, Eun-Ju;Hong, Sook-Hee;Lim, Young-Jin;Kim, Ki-Uk;Jeong, Min-Ho
    • Journal of Life Science
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    • v.16 no.6
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    • pp.904-910
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    • 2006
  • Dendritic cells (DCs) are the only antigen presenting cells (APCs) capable of initiating immune responses, which is crucial for priming the specific cytotoxic T lymphocyte (CTL) response and tumor immunity. Upon activation by DCs, CD4+ helper T cells can cross-prime CD8+ CTLs via IL-12. However, recently activated DCs were described to prime in vitro strong T helper cell type 1 $(Th_1)$ responses, whereas at later time points, they preferentially prime $Th_2$ cells. Therfore, we examined in this study the optimum kinetic state of DCs activation impacted on in vivo priming of tumor-specific CTLs by using ovalbumin (OVA) tumor antigen model. Bone-marrow-derived DCs showed an appropriate expression of surface MHC and costimulatory molecules after 6 or 7-day differentiation. The 6-day differentiated DCs pulsed with OVA antigen for 8 h (8-h DC) and followed by restimulation with LPS for 24 h maintained high interleukin (IL)-12 production potential, accompanying the decreased level in their secretion by delayed re-exposure time to LPS. Furthermore, immunization with 8-h DC induced higher intracellular $interferon(IFN)-{\gamma}+/CD8+T$ cells and elicited more powerful cytotoxicity of splenocytes to EG7 cells, a clone of EL4 cells transfected with an OVA cDNA, than immunization with 24-h DC. In the animal study for the evaluation of therapeutic or protective antitumor immunity, immunization with 8-h DC induced an effective antitumor immunity against tumor of EG7 cells and completely protected mice from tumor formation and prolonged survival, respectively. The most commonly used and clinically applied DC-based vaccine is based on in vitro antigen loading for 24 h. However, our data indicated that antigen stimulation over 8 h decreased antitumor immunity with functional exhaustion of DCs, and that the 8-h DC would be an optimum activation state impacted on in vivo priming of tumor-specific CTLs and subsequently lead to induction of strong antitumor immunity.

Targeted Therapies and Radiation for the Treatment of Head and Neck Cancer (두경부 암의 표적 지향적 방사선 치료)

  • Kim, Gwi-Eon
    • Radiation Oncology Journal
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    • v.22 no.2
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    • pp.77-90
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    • 2004
  • Purpose: The purpose of this review Is to provide an update on novel radiation treatments for head and neck cancer Recent Findings: Despite the remarkable advances In chemotherapy and radiotherapy techniques, the management of advanced head and neck cancer remains challenging. Epidermal growth factor receptor (EGFR) Is an appealing target for novel therapies In head and neck cancer because not only EGFR activation stimulates many important signaling pathways associated with cancer development and progression, and importantly, resistance to radiation. Furthermore, EGFR overexpression Is known to be portended for a worse outcome in patients with advanced head and neck cancer. Two categories of compounds designed to abrogate EGFR signaling, such as monoclonal antibodies (Cetuxlmab) and tyrosine kinase inhibitors (ZD1839 and 051-774) have been assessed and have been most extensively studied In preclinical models and clinical trials. Additional TKIs In clinical trials include a reversible agent, Cl-1033, which blocks activation of all erbB receptors. Encouraging preclinical data for head and neck cancers resulted In rapid translation Into the clinic. Results from Initial clinical trials show rather surprisingly that only minority of patients benefited from EGFR inhibition as monotherapy or In combination with chemotherapy. In this review, we begin with a brief summary of erbB- mediated signal transduction. Subsequently, we present data on prognostic-predictive value of erbB receptor expression in HNC followed by preclinlcal and clinical data on the role of EGFR antagonists alone or in combination with radiation In the treatment of HNC. Finally, we discuss the emerging thoughts on resistance to EGFR biockade and efforts In the development of multiple-targeted therapy for combination with chemotherapy or radiation. Current challenges for investigators are to determine (1 ) who will benefit from targeted agents and which agents are most appropriate to combine with radiation and/or chemotherapy, (2) how to sequence these agents with radiation and/or cytotoxlc compounds, (3) reliable markers for patient selection and verification of effective blockade of signaling in vivo, and (4) mechanisms behind intrinsic or acquired resistance to targeted agents to facilitate rational development of multi-targeted therapy, Other molecuiar-targeted approaches In head and neck cancer were briefly described, Including angloenesis Inhibitors, farnesyl transferase inhibitors, cell cycle regulators, and gene therapy Summary: Novel targeted theraples are highly appealing in advanced head and neck cancer, and the most premising strategy to use them Is a matter of intense Investigation.

Therapeutic Effect of Different Doses of Recombinant Human Granulocyte Colony-Stimulating Factor(rhG-CSF) on Neonatal Sepsis Complicated by Neutropenia (호중구 감소증이 합병된 신생아 패혈증에서 Recombinant Human Granulocyte Colony-Stimulating Factor(rhG-CSF)의 투여 용량에 따른 치료 효과)

  • Choi, Moon Young;Jung, Yeon Sook;Son, Dong Woo;Ahn, Hyo Seop
    • Clinical and Experimental Pediatrics
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    • v.45 no.4
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    • pp.439-448
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    • 2002
  • Purpose : The aim of this study is to determine and compare the effects of adjunctive therapy with different doses of recombinant human granulocyte-colony stimulating factor(rhG-CSF) on reversing sepsis-associated neonatal neutropenia, and their survival rate in a group I/II-type trial. Methods : RhG-CSF was injected subcutaneously to 10 septic-neutropenic neonates with doses of $10{\mu}g/kg$ from Oct. 1995 to Sep. 1996, and was administered to another 12 septic-neutropenic neonates with doses of $5{\mu}g/kg$ from Oct. 1996 to Sep. 1997. Neutrophilic responses and the outcomes of both groups were compared. Results : In the rhG-CSF $10{\mu}g/kg$ treated group and in the $5{\mu}g/kg$ treated group, the absolute neutrophil count(ANC) was $1,065{\pm}89$($mean{\pm}SEM$) and $1,053{\pm}131$, respectively. The only difference between the two groups was the peak ANC at 48 hours. Eight patients from the remaining nine of rhG-CSF $10{\mu}g/kg$ treated group(88.9%) and ten in $5{\mu}g/kg$ treated group(83.3%) survived the sepsis and were discharged without any problems. Conclusions : RhG-CSF can increase the neutrophil count in critically ill septic neutropenic neonats. The survival rate of both groups were up to 90%. This finding suggests that both doses of rhG-CSF may be effective in a therapeutically useful time frame to treat septic neonates with neonatal neutropenia attributable to bone marrow supression or neutrophil consumption.

Serum Phospholipid Fatty Acids in Benign Breast Tumor and Breast Cancer (양성 유방 종양과 유방암 환자의 혈청 인지질 지방산 조성)

  • Shim, Eu-Gene;Ahn, Sei-Hyun;Hwang, You-Jeong;Leekim, Yang-Cha
    • Journal of Nutrition and Health
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    • v.42 no.3
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    • pp.213-220
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    • 2009
  • Studies on the relationship between blood fatty acids and the risk of breast cancer have not yielded definite conclusions. The role of fatty acids in the development and progression of breast cancer is unclear. We conducted a case-control study to determine serum phospholipid fatty acid composition in benign breast tumor and breast cancer. Subjects consisted of 27 benign breast tumor and 68 breast cancer patients, and 28 matched controls. The levels of fatty acids were measured by gas chromatography. Higher arachidonic and palmitic acids were observed in breast cancer patients as compared with control and benign breast tumor patients. The percentage of total saturated fatty acids in breast cancer was higher than in control and benign breast tumor patients. The level of stearic acid was lower in benign breast tumor and breast cancer patients. Saturation index, the ratio of stearic to oleic acid, was lower in benign breast tumor and breast cancer patients compared to the control. Moreover, stearic acid was negatively and arachidonic acid was positively correlated with the cancer stage. In conclusion, our results support that serum phospholipid compositions of specific fatty acids are associated with the risk of benign breast tumor as well as breast cancer. Further studies are necessary to investigate mechanisms linked to the breast cancer etiology.

Influence of histologic chorioamnionitis and funisitis on the level of peripheral blood C-reactive protein at birth in preterm infants (조산아에서 조직학적 융모양막염 및 제대 혈관염이 출생 직후 말초 혈액 C-반응성 단백의 농도에 미치는 영향)

  • Kim, Do-Hyun;Lee, Heun Ji;Kim, Hee Sup;Yoo, Byoung Hoon
    • Clinical and Experimental Pediatrics
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    • v.53 no.1
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    • pp.33-40
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    • 2010
  • Purpose : The objective of this study is to determine the change of C-reactive protein (CRP) levels in the peripheral blood of preterm infants at birth according to the stage of intrauterine inflammation. Methods : A total of 187 infants (<32 weeks of gestation) were divided into a "no histologic chorioamnionitis" [HCAM (-), n=85] group and a "histologic chorioamnionitis" [HCAM (+), n=102] group according to placental pathologic findings. Furthermore, the HCAM (+) group was subdivided into a "funisitis" [F (+), n=49] group and a "no funisitis" [F (-), n=53] group and also into a "funisitis/amnionitis" [FA (+), n=58] group and an "isolated chorio-deciduitis" [FA (-), n=44] group. High-sensitivity CRP levels in the peripheral blood at birth were measured.Results : Peripheral blood CRP levels were significantly higher in the HCAM (+), F (+), F (-), and FA (+) groups than in the HCAM (-) group, but were not significantly different between the FA (-) and HCAM (-) groups. In addition, peripheral blood CRP levels were significantly higher in the F (+) and FA (+) groups than in the F (-) and FA (-) groups, respectively. For identification of amnionitis or funisitis, a cut-off value of 0.02 mg/dL was chosen. Clinical chorioamnionitis, proven early onset sepsis, histologic chorioamnionitis, and funisitis had higher incidences in infants with peripheral blood CRP levels higher than 0.02 mg/dL. Conclusion : The present study shows that peripheral blood CRP levels at birth in preterm infants born before 32 weeks' gestation is significantly increased in amnionitis or funisitis and might reflect the progress of histologic chorioamnionitis.

The Clinical Analysis of Sulcus Vocalis (성대구증에 관한 임상적 고찰)

  • 김광문;서장수;오혜경;최홍식;김기령
    • Proceedings of the KOR-BRONCHOESO Conference
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    • 1982.05a
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    • pp.11.2-12
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    • 1982
  • The major advancement in phonosurgery due to recent development of laryngomicrosurgery enabled more accurate diagnosis and treatment of patient with voice disorders. Among large proportion of voice disordered patients, prominent linear furrow running parallel along the free edge of vocal cord extending from the vocal process to anterior commissure can be seen as well as incomplete closure during phonation. These cases were illustrated and coined as sulcus vocalis by Salvi in 1901, since then other similar paper was reported in Europe and Japan, but has not been reported in Korea. The exact etiology and therapeutic methods of sulcus vocalis has not been elaborated. At Department of Otolaryngology of Yonsei University College of Medicine a series of voice analysis were performed among those 35 patients with sulcus vocalis visited to Vocal Dynamics Laboratory from May, 1981 to March, 1982. Following is the result of clinical statistical investgation and therapeutic modality. 1) The incidance of sulcus vocalis among 290 patients with voice disorder visited to Vocal Dynamics Laboratory was approximately 12%(35 cases). 2) Onset of this voice disorder was most frequent among patient under 10 year-old groups; 19 cases (54%) followed by second decade, third decade groups in decreasing frequency respectably. 3) The etiology of sulcus vocalis was mostly unknown. The sequelae after measle (4 cases) and severe upper respiratory infection (3 cases) and congenital deformity (2 cases) were the possible causes of sulcus vocalis. 4) These patients were involved bilaterally in 25 cases (71%), left side only in 8 cases (23%) and right side only in 2 cases (6%). 5) Almost all patients complained hoarseness and 7 patients were suffering from chronic laryngitis. 6) In aerodynamic analysis, Maximal Phonation Time was decreased in 20 cases (57%), Phonation Quotient was increased in 22 cases (63%) and Mean Air Flow Rate was increased in 23 cases (66%). 7) Among them, 33 cases were analyzed with stroboscopy. The findings were as follows; incomplete glottic closure during phonation in 31 cases (93%), regular vocal cord movement in whole cases, asymmetric cord movement in 4 cases (12%), decreased amplitude in 5 cases (21%) and small mucosal wave in 24 cases (73%). 8) Intracordal Teflon injection in 5 cases and Sulcusectomy in 1 cases were performed as therapeutic management, however, the therapeutic results were not effective except one case with Teflon injection.

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