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Imaging Neuroreceptors in the Living Human Brain

  • Wagner Jr Henry N.;Dannals Robert F.;Frost J. James;Wong Dean F.;Ravert Hayden T.;Wilson Alan A.;Links Jonathan M.;Burns H. Donald;Kuhar Michael J.;Snyder Solomon H.
    • The Korean Journal of Nuclear Medicine
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    • v.18 no.2
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    • pp.17-23
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    • 1984
  • For nearly a century it has been known that chemical activity accompanies mental activity, but only recently has it been possible to begin to examine its exact nature. Positron-emitting radioactive tracers have made it possible to study the chemistry of the human mind in health and disease, using chiefly cyclotron-produced radionuclides, carbon-11, fluorine-18 and oxygen-15. It is now well established that measurable increases in regional cerebral blood flow, glucose and oxygen metabolism accompany the mental functions of perception, cognition, emotion and motion. On May 25, 1983 the first imaging of a neuroreceptor in the human brain was accomplished with carbon-11 methyl spiperone, a ligand that binds preferentially to dopamine-2 receptors, 80% of which are located in the caudate nucleus and putamen. Quantitative imaging of serotonin-2, opiate, benzodiazapine and muscarinic cholinergic receptors has subsequently been accomplished. In studies of normal men and women, it has been found that dopamine and serotonin receptor activity decreases dramatically with age, such a decrease being more pronounced in men than in women and greater in the case of dopamine receptors than serotonin-2 receptors. Preliminary studies in patients with neuropsychiatric disorders suggests that dopamine-2 receptor activity is diminished in the caudate nucleus of patients with Huntington's disease. Positron tomography permits quantitative assay of picomolar quantities of neuro-receptors within the living human brain. Studies of patients with Parkinson's disease, Alzheimer's disease, depression, anxiety, schizophrenia, acute and chronic pain states and drug addiction are now in progress. The growth of any scientific field is based on a paradigm or set of ideas that the community of scientists accepts. The unifying principle of nuclear medicine is the tracer principle applied to the study of human disease. Nineteen hundred and sixty-three was a landmark year in which technetium-99m and the Anger camera combined to move the field from its latent stage into a second stage characterized by exponential growth within the framework of the paradigm. The third stage, characterized by gradually declining growth, began in 1973. Faced with competing advances, such as computed tomography and ultrasonography, proponents and participants in the field of nuclear medicine began to search for greener pastures or to pursue narrow sub-specialties. Research became characterized by refinements of existing techniques. In 1983 nuclear medicine experienced what could be a profound change. A new paradigm was born when it was demonstrated that, despite their extremely low chemical concentrations, in the picomolar range, it was possible to image and quantify the distribution of receptors in the human body. Thus, nuclear medicine was able to move beyond physiology into biochemistry and pharmacology. Fundamental to the science of pharmacology is the concept that many drugs and endogenous substances, such as neurotransmitters, react with specific macromolecules that mediate their pharmacologic actions. Such receptors are usually identified in the study of excised tissues, cells or cell membranes, or in autoradiographic studies in animals. The first imaging and quantification of a neuroreceptor in a living human being was performed on May 25, 1983 and reported in the September 23, 1983 issue of SCIENCE. The study involved the development and use of carbon-11 N-methyl spiperone (NMSP), a drug with a high affinity for dopamine receptors. Since then, studies of dopamine and serotonin receptors have been carried out in over 100 normal persons or patients with various neuropsychiatric disorders. Exactly one year later, the first imaging of opitate receptors in a living human being was performed [1].

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Lung Preservation Study for Above 20 Hours of LPDG Solution in Canine Lung Allotransplactation (폐이식 실험견에서 LPDG용액을 이용한 20시간 이상 폐보존효과 관찰)

  • Park, Chang-Gwon;Gwon, Geon-Yeong;Yu, Yeong-Seon
    • Journal of Chest Surgery
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    • v.30 no.10
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    • pp.949-960
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    • 1997
  • Background. Limited ischemic tolerance of the lung has remained one of the factors that limits the expansion of pulmonary transplantation as a treatment for end-stage pulmonary disease. Numerous studies on safe long term preservation for lung transplantation has been performed for the purpose of developing ideal preservation solution with extracellular type or intracellular type solutions. In this. study, we examined the efficacy of L DG solution in lung preservation longer than 20 hours by comparison with modified Euro-Collins solution. Iwethods. Thirty-(our adult mongrel dogs were divided into two groups. Donor lungs were flushed with LPDG solution(n=9) or modified Euro-Collins(MEC) solution(n=8) and stored for 24 hours at 1$0^{\circ}C$. All donor lungs were perfused through the pulmonary arteries with solutions containing prostaglandin El and verapamil. Left canine lung allotransplantations wereperformed. Assessment(hemodynamic indices and arterial blood gas analysis) of left implanted lung was made by occluding the right pulmonary artery for ten minutes using pulmonary artery Cuff. Assessment was repeated at the interval of 30 minutes, one hour, and two hours later after reperfusion and then chest X-ray, computed tomogram and lung perfusion scan were obtained. In survival dogs follow-up studies were done with assessment with chest X-ray, computed tomogram of the chest and lung perfusion scan on 7th day postoperatively. After preservation above 20 hours, pathological examinations for ultrastructural findings on right lung were performed in each group. Results. With respect to arterial oxygen tension, LPDG group was superior to MEC but there was no statistical significance for 2 hours after reperfusion. Mean pulmonary artery pressure was less increased(p < 0.05) and cardiac output higher(p <0.05) than MEC group until 2 hours after reperfusion. After 2 hours of reperfusion, both groups showed transplanted lung function deteriorated gradually. Perfusion scan of the transplanted lung in LPDG group showed better perfusion rate in immediate post-reperfusion, 3 days and 7 days later respectively but there was no statistical significance and corelation with PaO2 and computed tomoRravhic views. In scanning electron microscopy of pulmonary artery after preservation, LPDG group relatively shows less irregular protrusion of the inner surface of endothelial cell of poulmonary artery than MEC group. Conclusions, e concluded that LPDG solution can offer safe lung preservation above 20 hours with adequate immunosuppressive therapy and prevention of the infection.

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Effect of Reperfusion after 20 min Ligation of the Left Coronary Artery in Open-chest Bovine Heart: An Ultrastructural Study (재관류가 허혈 심근세포의 미세구조에 미치는 영향 : 재관류 손상에 관한 연구)

  • 이종욱;조대윤;손동섭;양기민;라봉진;김호덕
    • Journal of Chest Surgery
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    • v.31 no.8
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    • pp.739-748
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    • 1998
  • Background: It has been well documented that transient occlusion of the coronary artery causes myocardial ischemia and finally cell death when ischemia is sustained for more than 20 minutes. Extensive studies have revealed that ischemic myocardium cannot recover without reperfusion by adequate restoration of blood flow, however, reperfusion can cause long-lasting cardiac dysfunction and aggravation of structural damage. The author therefore attempted to examine the effect of postischemic reperfusion on myocardial ultrastructure and to determine the rationales for recanalization therapy to salvage ischemic myocardium. Materials and methods: Young Holstein-Friesian cows(130∼140 Kg body weight; n=40) of both sexes, maintained with nutritionally balanced diet and under constant conditions, were used. The left anterior descending coronary artery(LAD) was occluded by ligation with 4-0 silk snare for 20 minutes and recanalized by release of the ligation under continuous intravenous drip anesthesia with sodium pentobarbital(0.15 mg/Kg/min). Drill biopsies of the risk area (antero-lateral wall) were performed at just on reperfusion(5 minutes), 1-, 2-, 3-, 6-, 12-hours after recanalization, and at 1-hour assist(only with mechanical respiration and fluid replacement) after 12-hour recanalization. The materials were subdivided into subepicardial and subendocardial tissues. Tissue samples were examined with a transmission electron microscope (Philips EM 300) at the accelerating voltage of 60 KeV. Results: After a 20-minute ligation of the LAD, myocytes showed slight to moderate degree of ultrastructural changes including subsarcolemmal bleb formation, loss of nuclear matrix, clumping of chromatin and margination, mitochondrial destruction, and contracture of sarcomeres. However, microvascular structures were relatively well preserved. After 1-hour reperfusion, nuclear and mitochondrial matrices reappeared and intravascular plugging by polymorphonuclear leukocytes or platelets was observed. However, nucleoli and intramitochondrial granules reappeared within 3 hours of reperfusion and a large number of myocytes were recovered progressively within 6 hours of reperfusion. Recovery was apparent in the subepicardial myocytes and there were no distinct changes in the ultrastructure except narrowed lumen of the microvessels in the later period of reperfusion. Conclusions: It is likely that the ischemic myocardium could not be salvaged without adequate restoration of coronary flow and that the microvasculature is more resistant to reversible period of ischemia than subendocardium and subepicardium. Therefore, thrombolysis and/or angioplasty may be a rational method of therapy for coronarogenic myocardial ischemia. However, it may take a relatively longer period of time to recover from ischemic insult and reperfusion injury should be considered.

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Effects of Deletion of Supplementary Vitamins and Trace Minerals on Performance, Muscle Vitamin E and Fecal Trace Mineral Contents in Finishing Pigs (비육후기 사료에서 비타민-미량광물질 첨가제의 제거가 돼지의 성장 능력, 근육 내 비타민 E 및 분 중 미량광물질 함량에 미치는 영향)

  • Lee, S.C.;Lee, C.E.;Kim, K.I.
    • Journal of Animal Science and Technology
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    • v.45 no.4
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    • pp.543-550
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    • 2003
  • Two experiments were conducted to determine the effects of deletion of vitamin and trace mineral premixes on growth, feed efficiency, backfat thickness, hemoglobin content, muscle vitamin E content, and fecal, serum and muscle trace mineral contents in finishing pigs raised under two different housing conditions. In Exp. 1, three pens (or experimental units) of five pigs each (average weight $\pm$ s.e., 70 $\pm$ 0.5 kg) were assigned to a control diet (with vitamin and trace mineral premixes) or diets with 50 or 100% of the premixes deleted. Pigs were fed to market weight under sub-optimal housing conditions with sawdust-covered concrete floor and no electrical ventilation. In Exp. 2, three pens of four pigs each (average weight $\pm$ s.e., 56 $\pm$ 1.1 kg) were assigned to a control (with vitamin and trace mineral premixes), Diet-P (100% of the premixes deleted) or Diet-P+E (Diet-P plus 100 mg $\alpha$-tocopherol acetate/kg diet fed for the last 2 wk before slaughter). Pigs were fed to market weight under optimal housing conditions with 70%-slatted concrete floor, electrical ventilation and temperature control. No significant differences were found in average daily gain (ADG), average daily feed intake (ADFI), and gain/feed among treatments in both experiments, but in Exp. 2 done with younger pigs, ADG and ADFI tended to be higher in the control group than in pigs fed diet without premixes. Hemoglobin content, hematocrit and red blood cell count were not influenced by the deletion of premixes. Backfat thickness was not different among treatments. Fecal Mn (twofold) and Zn (threefold) contents were higher in the control than in pigs fed diets without the premixes. Serum trace mineral contents were not influenced by diets. $\alpha$-Tocopherol content in gluteus maxima was decreased (P< 0.01) by deleting the dietary premixes, but increased to the level higher than the control by adding 100 mg $\alpha$-tocopheryl acetate/kg diet fed for the last 2 wk before slaughter. Results indicate that: 1) supplementary vitamins and trace minerals may not be necessary for optimum growth in finishing pigs, and 2) deletion of the dietary premixes reduces muscle vitamin E content, but the reduced content can be reversed by adding $\alpha$- tocopherol to diets fed for the last 2 wk before slaughter. The deletion may help to alleviate the environmental load of certain minerals from manure.

Toll-like receptor 9 expression and interferon-α secretion upon CpG-ODN stimulation in allergic subjects (알레르기 환자에서 TLR9 ligand인 CpG-ODN 자극에 의한 IFN-α 분비와 TLR9 발현)

  • Han, Man Yong;Jee, Hye Mi;Kim, Hyeong Yoon;Lee, Cho Ae;Cho, Hyo-Jin;Hwang, Seong-Gyu;Kim, Kyu-Earn
    • Clinical and Experimental Pediatrics
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    • v.52 no.9
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    • pp.1015-1020
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    • 2009
  • Purpose:The aim of this study is to explore the effect of the Toll-like receptor 9 (TLR9) expressed in plasmacytoid dendritic cells (pDCs) that respond to antigen to Th2 immune deviation in allergic patients. Methods:Subjects consisted of 19 allergic patients and 17 healthy volunteers. Skin prick tests and nasal provocation tests were performed for the two groups. Peripheral blood mononuclear cells (PBMCs) were collected from subjects and analyzed for the Lineage Cocktail (CD3, CD14, CD16, CD19, CD20, CD56) (-), HLA-DR (+), and CD123 (+) using flow cytometry. In addition, we analyzed TLR9 mRNA by reverse transcriptase-polymerase chain reaction. The level of $interferon-{\alpha}$ ($IFN-{\alpha}$) of the PBMCs following stimulation with the TLR9 ligand CpG-ODN 2216 was also evaluated. Results:Analyses of CD123 (+) revealed a nearly similar distribution for the classical pDC markers in the allergic group ($0.1%{\pm}0.04%$) and in the controls ($0.25%{\pm}0.23%$). The mRNA levels of TLR9 on PBMCs were not different between the allergic group and the controls ($1.29{\pm}0.41$ vs. $1.25{\pm}0.23$, respectively). Additionally, the level of $IFN-{\alpha}$ in PBMCs exposed to stimuli of the TLR9 ligand CpG-ODN 2216 was not significantly different between the two groups ($911{\pm}829$ vs. $1,095{\pm}888pg/mL$, respectively). Conclusion:We found no evidence that TLR9-dependent immune responses in human pDCs are associated with allergic status.

A Comparative Study of Therapeutic Effect of Aspirin Alone and Intravenous Gammaglobulin Plus Aspirin in Kawasaki Disease (Kawasaki병에 있어 아스피린 단독 투여시와 정맥내 감마 글로불린 병용시에 치료효과에 대한 연구)

  • Hwang, Young-Hee;Jun, Jin-Gon;Kim, Chun-Dong
    • Journal of Yeungnam Medical Science
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    • v.9 no.1
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    • pp.44-53
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    • 1992
  • We compared the efficacy of each modality of treatment group in reducing the frequency of coronary artery abnormalities and changes of clinical courses in children with kawasaki disease in the children of 81 cases who were admitted in pediatric department of Yeungnam University Hospital from September 1985 to August 1990, Group A(37 cases)-aspirin alone, Group B(44 cases)-intravenous gammaglobulin(400mmg/kg/day) for 5 consecutive days, plus aspirin. We studied the frequency of echocardiographic abnormalities, the duration of fever, and changes in the total white blood cell counts, platelet counts, ESR and CRP value at 1, 2 and 3 weeks of the illness and compared the results between the two groups. The results were as follows, 1) There as no significant intergroup difference in age and sex ratio. 2) The duration of the febrile period after the initiation of the therapy was significant shorter in group B($2.5{\pm}1.2$ days) than in group A:($5.2{\pm}3.5$ days)(p<0.01). 3) No significant difference was noticed in the WBC and platelet counts in two groups as measured at admission day, 1 and 2 weeks of the illness. However, at 3weeks of illness significant difference was noted. 4) The CRP values measured at 1, 2 and 3 weeks after treatment were significantly lower in group B($2.42{\pm}1.8$, $2.00{\pm}1.2$, $1.16{\pm}1.0$) than in group A($7.22{\pm}5.3$, $5.25{\pm}3.9$, $1.85{\pm}1.2$) respectively(p<0.01). 5) In 2D- Echocardiogram, coronary artery dilataton was more frequent in Group A than in Group B at 6month of illness(p<0.01). In conclusion, intravenous gammaglobulin therapy was effective in the shortening of the duration of fever and in the antiinflammatory action and somewhat effective in prevention of coronary artery aneurysm.

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Magnetic resonance imagining findings of the white matter abnormalities in the brain of very-low-birth-weight infants (극소 저체중 출생아에서 뇌백질 병변의 MRI 소견)

  • Choi, Jae Hyuk;Chang, Young Pyo
    • Clinical and Experimental Pediatrics
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    • v.52 no.10
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    • pp.1127-1135
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    • 2009
  • Purpose : To observe the abnormal white matter findings on the magnetic resonance imaging (MRI) scans of very-low- birth-weight (VLBW) infant brains at term-equivalent age and to determine the clinical risk factors for the development of periventricular leukomalacia (PVL). Methods : In all, MRI was performed in 98 VLBW infants and the white matter abnormalities were observed. Clinical risk factors for cystic and noncystic PVL were determined. Results : MRI scans of 74 infants (75.5%) showed diffuse excessive high signal intensity (DEHSI) in the periventricular white matter, 17 (17.3%) lateral ventricle dilation, 5 (5.1%) and 11 (11.2%) focal punctate lesions and cystic changes in the periventricular white matter, respectively, 9 (9.1%), germinal layer hemorrhage (GLH) or subependymal cysts 3 (3.1%) intraventricular hemorrhage (>grade 2) 2 (2.0%) posthemorrhagic hydrocephalus and 2 (2.0%) periventricular hemorrhagic infarct. Gestational age (GA), 1-minute Apgar score, Clinical Risk Index for Babies-II (CRIB-II) score, and inotrope use, and GA, CRIB-II score, postnatal steroid administration, inotrope use, and abnormal white blood cell (WBC) count at admission were related to cystic PVL and noncystic PVL development, respectively (P<0.05). However, in logistic regression analysis, CRIB-II (odds ratio, 1.63, 295% confidence interval, 1.15-2.30 P=0.006) for cystic PVL, and GA (odds ratio 0.90, 95% confidence interval, 0.82-0.99 P=0.036) for noncystic PVL were only significant independently. Conclusion : White matter abnormalities could be observed on MRI scans of the VLBW infant brains at term-equivalent age, and CRIB-II and GA were only independently significant for cystic and noncystic PVL development, respectively.

The effectiveness of biochemical indexes for evaluating the nutrition states of children (소아에서 영양평가로서 생화학적 지표의 유용성)

  • Kim, Jae Kwang;Jin, Hyun Seong;Han, Myung Ki;Kim, Bong Seong;Cha, Choong Hwan;Park, Kie Young
    • Clinical and Experimental Pediatrics
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    • v.52 no.2
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    • pp.167-175
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    • 2009
  • Purpose : This study has been conducted to analyze whether the biochemical nutrition indexes might be useful and effective for evaluating the nutrition states of children. Methods : We evaluated 269 children, aged 3-9 years old, who had visited Gangneung Asan Hospital for elective surgery from January 2006 to December 2007, and examined their anthropometric and preoperative laboratory data with retrospective analysis. The children were classified into underweight, normal weight, overweight, and obese groups according to body mass index (BMI). The biochemical nutrition indexes (total lymphocyte count (TLC), hemoglobin, hematocrit, serum albumin, cholesterol, et al) of each group were then analyzed statistically. Results : None of the groups showed statistically significant differences in TLC. Serum albumin decreased significantly in the underweight group. Red blood cell (RBC) count, hemoglobin, hematocrit, and serum total cholesterol in the obese group were higher than in the normal weight group. None of the groups showed statistically significant increase in mean corpuscular volume or mean corpuscular hemoglobin, and it seems that the increase of hemoglobin and RBC count in the overweight and obese groups is due to the enhancement of erythropoiesis rather than iron metabolism. However, in females, almost all nutrition indexes except albumin were statistically significantly poor. Conclusion : Serum albumin, total cholesterol, RBC count, hemoglobin, and hematocrit were useful as nutrition indexes. However, except for albumin, these indexes were significantly poor for females. More control studies are needed to confirm the effectiveness of biochemical indexes for evaluating the nutritional state of children.

The Interactive Significance of Red in Film Color : Concentration and Diffusion (영화에서 빨강의 상호작용적 의미 : 집중과 확산)

  • Kim, Jong-Guk
    • Cartoon and Animation Studies
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    • s.47
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    • pp.241-271
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    • 2017
  • Film color is equivalent to other elements of film, including narrative, and has a textual meaning according to the identity of expression. In general, red has a function of focusing attention, and the meaning derived from it is diffused. In the interaction of text and context, the function of concentration and the meaning of diffusion can be presented. The concept of concentration and diffusion is shaped by the relationship between independent colors, colors and other cinematic elements, and interactions between colors. In order to confirm this, this study analyzes a series of popular Korean films, how film colors interact, and in particular, the concentration function of red and the meaning of proliferation. The results of this study are as follows. First, in Korean popular films, at its most basic, red symbolizes a nation, a people, and a nation. The red of nationalism surrounding ethnicity, nationality and country visualizes ideology and conflict. The purpose of an individual or group, the relationship between the offender and the victim is mediated through red. The flag, the name tag, the costume appearing in the film are red. This can be seen in films such as Train to Busan, Assassination, Masquerade, Miracle in Cell No.7, Brotherhood of War, Northern Limit Line, Joint Security Area, Welcome to Dongmakgol, and May 18. Second, the red color attached to the female body fixes or strengthens socio-cultural sexuality and gender. The examples are films like Ode to My Father, The Thieves, The Host, Purpose Of Love, Sunny, Like A Virgin, Forbidden Quest, Untold Scandal, Bewitching Attraction, and Ssanghwajeom. Third, the blood red in Korean films is a visual device that directs magical horror, anger, and asceticism. Such films include The Neighbors, Bunshinsaba, R-Point, A Tale Of Two Sisters, Whispering Corridors, The Uninvited, Thirst, SECTOR 7, Asura:The City of Madness, The Tiger, Veteran, and so on. Fourth, red of tears constitutes the specific emotions such as a beautiful desire and a brilliant tragedy in films like King and The Clown, Oldboy, Memories of Murder, 26 Years, The Attorney, Unbowed, Sympathy For Lady Vengeance, Happy End, Punch, Calling, The Yellow Sea, and He's on Duty.

The Effect of Hyperthermia Combined with Radiation on Crypts of the Mouse Jejunum (마우스공장 소낭선의 방사선 효과에 온열요법의 병용이 미치는 영향에 관한 실험적 연구)

  • Bae, Hoon-Sik;Park, Charn-Il;Kim, Jung-Jin
    • Radiation Oncology Journal
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    • v.5 no.1
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    • pp.13-21
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    • 1987
  • The effect of local hyperthermia of 41 to $43^{\circ}C$ for 30 minutes on radiosensitivity of normal tissue was studied utilizing jejunal crypt microcolony assay. Hyperthermia of this range enhanced the radiation effect and the effect was mainly additive without significant effect on the slopes of cell survival curves. At the isoeffect level of 20 microcolony formation, the thermal enhancement ratio was 1.02, 1.10 and 1.39 for $41^{\circ},\;42^{\circ}\;and\;43^{\circ}C$, respectively. The distribution of microcolony formation along the circumference of jejunum was not uniform, having more colonies around the mesenteric border, and this suggests the effect of uneven cooling by blood circulation.

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