• Title/Summary/Keyword: 비정상 전도

Search Result 1,161, Processing Time 0.036 seconds

Antihypertensive Effect of Peptide from Sardine Muscle Hydrolyzate on Mild Hypertensive Subjects (정어리 단백질 유래 펩타이드의 경중 고혈압 환자에 대한 강압효과)

  • Kawasaki, T.;Seki, E.;Osajima, K.;Yoshida, M.;Asada, K.;Matsui, T.;Osajima, Y.
    • Proceedings of the Korean Society of Food Hygiene and Safety Conference
    • /
    • 2004.11a
    • /
    • pp.50-58
    • /
    • 2004
  • Valy-Tyrosine (VY) derived from alkaline pretense hydrolyzate of sardine muscles showed the in vitro Angiotensin I converting enzyme (ACE) inhibitory activity and the in vivo antihypertensive effect in SHR. We investigated the antihypertensive effect of the VY on mild hypertensive subjects including subjects with high-normal blood pressure using a randomized double-blind placebo-controlled study. (1) Nineteen subjects (Age 48.9${\pm}$4.3, M/F;18/1) took a 100ml drink either containing 125${\mu}$g of VY or placebo twice daily for 4 weeks. The reductions of the systolic (SBP) and diastolic blood pressure (DBP) were observed in mild hypertensive subjects (n=5) with averages of 17.8${\pm}$2.5 mmHg (p<0.01 vs placebo) and 11.0${\pm}$2.0 mmHg(p<0.05 vs placebo), respectively. Neither SBP nor DBP changed in the subjects of both the placebo group and the high-normal blood pressure group. (2) A randomized double-blind cross-over placebo-controlled study was carried out in 10 mild essential hypertensive subjects (Age 50.6${\pm}$4.6, M/F;10/0). They took a 100ml drink either containing 62.5${\mu}$g of VY or placebo twice daily for 4 weeks alternatively with a 6-week interval. The percent changes in SBP and DBP were -6.9 % and -5.8 % (p<0.05) one week after the VY drink administration, respectively. No adverse effects such as coughing or allergic phenomena could be observed in any of the subjects of drinking VY during the experimental period. These results suggest that the drink containing at least 125${\mu}$g/day of VY may have a significant antihypertensive effect on mild hypertensive subjects without any adverse effects.

  • PDF

Effect of Aprepitant in Patient with Gastroparesis and Related Disorders (위마비증과 만성 구역 구토 증후군 환자에서 Aprepitant의 효과)

  • Jung, Kyoungwon;Park, Moo In
    • The Korean Journal of Gastroenterology
    • /
    • v.72 no.6
    • /
    • pp.325-328
    • /
    • 2018
  • 위마비증(gastroparesis)이나 만성 구역 구토 증후군(chronic unexplained nausea and vomiting)으로 인한 구역과 구토에 대한 치료는 일반적으로 사용하는 위장관 촉진제에 만족스럽지 못한 경우가 많고, 여러 부작용으로 인하여 장기적으로 사용하기 어려워 보다 효과적인 치료 방법이 필요하다. 최근 미국에서 발표된 본 연구는 위마비증이나 연관 증후군 환자에서 구역과 구토 증상을 줄이기 위한 aprepitant(neurokinin-1 receptor antagonist) 치료의 효과를 분석한 것으로, 향후 일반적인 치료에 불응성 위마비증 환자에서 새로운 약제 사용을 시도해볼 수 있어 소개하고자 한다. 본 Aprepitant for the Relief of Nausea (APRON) 연구는 기질적 질환을 배제하기 위하여 최근 2년 이내 위내시경이 정상이며, 적어도 6개월 이상 조기 포만감(early satiety), 식후 만복감(postprandial fullness), 팽만감(bloating) 그리고 명치부 통증(epigastric pain)을 유발하는 증상과 함께 만성적인 구역이 있는 18세 이상의 성인 중 4시간의 위배출 검사를 시행받은 환자를 대상으로 하였다. 객관적인 지표로 0점에서 45점까지 보이는 9-증상 Gastroparesis Cardinal Symptom Index(GCSI)가 2주 이상 총 21점 이상이며, 0-100 mm의 visual analog scale (VAS)의 7일간의 구역 증상 평균 25 mm 이상인 환자를 대상으로 하였다. 일주일에 3일 이상 narcotics를 사용하였거나 와파린이나 pimozide, terfenadien, astemizole, cisapride를 복용하였던 환자, 2배 이상으로 간 효소 수치상승을 보이거나 Child-Pugh score 10점 이상, aprepitant에 알레르기를 보이는 환자는 제외되었다. 그렇지만 metoclopramide나 erythromycin을 안정적으로 사용 중인 환자는 제외되지 않았다. 위배출 검사는 2시간에서 60% 이상 남아 있거나 4시간에서 10% 이상 남아 있는 경우에 지연된 것으로 정의되었으며, 지연된 위배출 검사 결과 자체는 환자의 등록 기준에 포함되진 않았다. 등록 기준에 포함된 환자는 1:1로 무작위 배정되어 하루 한 번 125 mg의 aprepitant 복용군과 위약군으로 나누어져 연구가 진행되었으며, 약제 복용 4주간 2주 간격으로, 그리고 복용 후 2주 뒤까지 구역 증상의 호전 정도와 약제 안전성을 확인하였다. 이러한 효과를 판정하기 위하여 환자가 방문하는 동안 GCSI를 포함한 Patient Assessment of Upper GI Symptoms (PAGI-SYM), Gastrointestinal Symptom Rating Scale, daily VAS, daily diary version of the GCSI 그리고 정신 측정 도구와 삶의 질 도구인 Patient health Questionnaire 15와 Short Form 36 version이 측정되었다. 구역에 대한 aprepitant와 위약의 치료 효과의 일차적 판정은 이전 항암 요법에 대한 aprepitant 연구와 같이 28일 평균 VAS 25 mm 미만이거나 치료 전 7일간의 VAS와 비교하여 28일 치료 기간 동안 25 mm 이상 감소한 경우로 정의하였고, 이차 결과는 구역의 매일 시간, 치료 중 구역이 없는 날짜의 퍼센트, PAGI-SYM score의 개선 등으로 확인하였다. 2013년 4월부터 2015년 7월까지 총 126명의 환자가 등록되어 aprepitant군 63명, 위약군 63명으로 무작위 배정되었다. 전체의 57%인 72명에서 위배출 지연이 보였으며, 나머지 43%에서는 정상 또는 빠른 위배출 소견을 보여 만성적으로 설명할 수 없는 구역과 구토에 포함된 환자군으로 확인되었다. 또한 29%에서 당뇨를 가지고 있었으며, 8%에서 수면제를 사용하고 있었다. 최종적으로 aprepitant군은 59명, 위약군은 63명이 연구를 끝까지 종료하였다. 일차 결과에서 aprepitant 군 46%, 위약군 40%의 구역 호전을 보여 두 치료군 간에 통계적으로 의미 있는 차이는 보이지 않았다(상대 위험도 1.2, 95% CI: 0.8-1.7; p=0.43). 그러나 일차 분석의 두 가지 척도(28일 평균 VAS 25 mm 미만과 기저 VAS보다 평균 28일 VAS의 25 mm 이상 감소)를 모두 함께 고려한 민감도 분석에서는 aprepitant군이 37% (22/59)로 위약군의 17%(11/63)에 비하여 통계적으로 의미 있는 구역의 호전을 보였다(상대 위험도 2.1, 95% CI: 1.1-4.1; p=0.01). 또한 이차 분석을 살펴보면 aprepitant군에서 PAGI-SYM 중증도 지수로 확인하였을 때, 구역(1.8 vs. 1.0; p=0.005)과 구토(1.6 vs. 0.5; p=0.001)의 중증도 및 매일 구역 시간의 감소를 보였고, 28일 동안 구역이 없는 날짜의 퍼센트 증가 소견을 보였다. 다른 이차 결과 분석에서 aprepitant군이 PAGI-SYM 중증도 지수의 GCSI 종합 점수(1.3 vs. 0.7; p=0.001), 상당한 증상호전, 구역 구토의 세부 점수, 팽만감 세부 점수 그리고 위식도 역류 증상 점수에서 호전을 보였고, 매일 일기로 표현한 daily diary version of the GCSI에 상복부 통증 중증도, 전체 증상 그리고 Gastrointestinal Symptom Rating Scale의 종합 점수에서 호전을 보였다. 연구 중 발생한 부작용은 주로 경증과 중등도 정도의 부작용이 주로 발생하였지만, aprepitant군(35% vs. 17% 위약군, p=0.04)에서 더 많이 발생하였다. 결론적으로 위마비증 또는 위마비증 유사 증후군으로 인한 만성 구역 및 구토 환자의 무작위 시험에서 aprepitant는 VAS 점수를 통한 주요 결과를 분석하였을 때는 구역의 중증도를 호전시키지 못하였지만 다른 이차적 결과에 대해서는 위약군에 대하여 호전 소견을 보였다. 따라서 aprepitant에 효과적인 반응을 보이는 위마비증 환자를 감별하는 추가 임상시험이 필요할 것으로 판단된다.

A Study on Farmer's Syndrome and Its Risk Factors of Vinyl House Worker and Farmer in a Rural Area (일부 농촌지역 비닐하우스 재배자들의 농부증 실태와 관련요인)

  • Lee, In-Bae;Lee, Yeon-Kyeong;Chang, Sung-Sil;Lee, Sok-Goo;Cho, Young-Che;Lee, Dong-Bae;Lee, Tae-Yong
    • Journal of agricultural medicine and community health
    • /
    • v.24 no.1
    • /
    • pp.13-33
    • /
    • 1999
  • The aim of this study was to investigate fatigue scores, physical complaints, farmer's syndrome and to find out its risk factors among farmers. The questionnaire survey was conducted to 177 vinyl house workers and 213 farmers who lived in Chongyang gun of Chungnam province from February 24 to March 15, 1998. The obtained main results were followings; 1. The fatigue scores were not significantly different between vinyl house workers and farmers. The fatigue scores were higher in female group, lower education group, shorter sleep hours group(under 8 hours), nonsmoker, nondrinker group than otherwise groups. There was not statistically significant difference between the mean fatigue scores and age, eating habit and body mass index. Duration of farming years in vinyl house and farming area and number of farming workers in farmers family showed a slight relationship with the fatigue score. 2. Health scores were not different between vinyl house workers and farmers. The health states was poorer in female group, lower education group, shorter sleep hours group(under 8 hours), nonsmoker group, and nondrinker group than otherwise groups by health scores. Health scores were not related with age, eating habit and body mass index. 3. The proportion of farmer's syndrome was 49.1% in vinyl house workers and 52.1% in farmers. That was higher in female than in male and the higher proportion was found in the lower education group of vinyl house workers and farmers. The proportion of farmer's syndrome was higher in the group of smoker, alcohol drinkers and over or under weight in vinyl house workers, but did not differ in those of farmers. 4. By multiple logistic regression, sex and sleep hours were risk factors affecting to farmer's syndrome. Odds ration for female group was 2.53 (reference group was male) and that for over 8 sleep hours group was 0.74 (reference group was under 8 sleep hours group). 5. The chief complaints by CMI were "I am difficult to work due to aching the back and the limbs", "I feel prickle pain in the limbs", "I sometimes have a twinge in the limbs", "I am not quite well as having a pain in the limbs", "I feel weaker grasping power than before" in both of vinyl house workers and farmers. Vinyl house workers more frequently pointed out skin darkening, skin disease and hemorrhoids than farmers. 6. According to correspondence analysis, skin disease of vinyl house workers was related to vinyl house farmers and digestive and general symptom was associated with male and endocrinological and muscular symptom was associated with female in vinyl house workers. And it revealed that farmer's syndrome was highly related with female and farmers relatively. By the above results, the fatigue scores, perceive health and farmer's syndrome did not much differ in two groups, but aged female farmers should be considered as female farmers represented higher fatigue score, farmers syndrome and poorer perceive health than male farmers in addition to farmer's syndrome was increased with ageing process. Also feeble but distinguished symptoms which might be due to working environment were observed especially in vinyl house workers and that should be considered and investigated continuously.

  • PDF

Effect of Acutely Increased Glucose Uptake on Insulin Sensitivity in Rats (단기간의 당섭취 증가가 인슐린 감수성에 미치는 영향)

  • Kim, Yong-Woon;Ma, In-Youl;Lee, Suck-Kang
    • Journal of Yeungnam Medical Science
    • /
    • v.14 no.1
    • /
    • pp.53-66
    • /
    • 1997
  • Insulin resistance is a prominent feature of diabetic state and has heterogeneous nature. However, the pathogenetic sequence of events leading to the emergence of the defect in insulin action remains controversial. It is well-known that prolonged hyperglycemia and hyperinsulinemia are one of the causes of development of insulin resistance, but both hyperglycemia and hyperinsulinemia stimulate glucose uptake in peripheral tissue. Therefore, it is hypothesized that insulin resistance may be generated by a kind of protective mechanism preventing cellular hypertrophy. In this study, to evaluate whether the acutely increased glucose uptake inhibits further glucose transport stimulated by insulin, insulin sensitivity was measured after preloaded glucose infusion for 2 hours at various conditions in rats. And also, to evaluate the mechanism of decreased insulin sensitivity, insulin receptor binding affinity and glucose transporter 4 (GLUT4) protein of plasma membrane of gastrocnemius muscle were assayed after hyperinsulinemic euglycemic clamp studies. Experimental animals were divided into five groups according to conditions of preloaded glucose infusion: group I, basal insulin ($14{\pm}1.9{\mu}U/ml$) and basal glucose ($75{\pm}0.7mg/dl$), by normal saline infusion; group II, normal insulin ($33{\pm}3.8{\mu}U/ml$) and hyperglycemia ($207{\pm}6.3mg/dl$), by somatostatin and glucose infusion; group III, hyperinsulinemia ($134{\pm}34.8{\mu}U/ml$) and hyperglycemia ($204{\pm}4.6mg/dl$), by glucose infusion; group IV, supramaximal insulin ($5006{\pm}396.1{\mu}U/ml$) and euglycemia ($l00{\pm}2.2mg/dl$), by insulin and glucose infusion; group V, supramaximal insulin ($4813{\pm}687.9{\mu}U/ml$) and hyperglycemia ($233{\pm}3.1mg/dl$), by insulin and glucose infusion. Insulin sensitivity was assessed with hyperinsulinemic euglycemic clamp technique. The amounts of preloaded glucose infusion(gm/kg) were $1.88{\pm}0.151$ in group II, $2.69{\pm}0.239$ in group III, $3.54{\pm}0.198$ in group IV, and $4.32{\pm}0.621$ in group V. Disappearance rates of glucose (Rd, mg/kg/min) at steady state of hyperinsulinemic euglycemic clamp studies were $16.9{\pm}3.88$ in group I, $13.5{\pm}1.05$ in group II, $11.2{\pm}1.17$ in group III, $13.2{\pm}2.05$ in group IV, and $10.4{\pm}1.01$ in group V. A negative correlation was observed between amount of preloaded glucose and Rd (r=-0.701, p<0.001) when all studies were combined. Insulin receptor binding affinity and content of GLUT4 were not significantly different in all experimental groups. These results suggest that increased glucose uptake may inhibit further glucose transport and lead to decreased insulin sensitivity.

  • PDF

Usefulness of Non-coplanar Helical Tomotherapy Using Variable Axis Baseplate (Variable Axis Baseplate를 이용한 Non-coplanar 토모테라피의 유용성)

  • Ha, Jin-Sook;Chung, Yoon-Sun;Lee, Ik-Jae;Shin, Dong-Bong;Kim, Jong-Dae;Kim, Sei-Joon;Jeon, Mi-Jin;Cho, Yoon-Jin;Kim, Ki-Kwang;Lee, Seul-Bee
    • The Journal of Korean Society for Radiation Therapy
    • /
    • v.23 no.1
    • /
    • pp.31-39
    • /
    • 2011
  • Purpose: Helical Tomotherapy allows only coplanar beam delivery because it does not allow couch rotation. We investigated a method to introduce non-coplanar beam by tilting a patient's head for Tomotherapy. The aim of this study was to compare intrafractional movement during Tomotherapy between coplanar and non-coplanar patient's setup. Materials and Methods: Helical Tomotherapy was used for treating eight patients with intracranial tumor. The subjects were divided into three groups: one group (coplanar) of 2 patients who lay on S-plate with supine position and wore thermoplastic mask for immobilizing the head, second group (non-coplanar) of 3 patients who lay on S-plate with supine position and whose head was tilted with Variable Axis Baseplate and wore thermoplastic mask, and third group (non-coplanar plus mouthpiece) of 3 patients whose head was tilted and wore a mouthpiece immobilization device and thermoplastic mask. The patients were treated with Tomotherapy after treatment planning with Tomotherapy Planning System. Megavoltage computed tomography (MVCT) was performed before and after treatment, and the intrafractional error was measured with lateral(X), longitudinal(Y), vertical(Z) direction movements and vector ($\sqrt{x^2+y^2+z^2}$) value for assessing overall movement. Results: Intrafractional error was compared among three groups by taking the error of MVCT taken after the treatment. As the correction values (X, Y, Z) between MVCT image taken after treatment and CT-simulation image are close to zero, the patient movement is small. When the mean values of movement of each direction for non-coplanar setup were compared with coplanar setup group, X-axis movement was decreased by 13%, but Y-axis and Z-axis movement were increased by 109% and 88%, respectively. Movements of Y-axis and Z-axis with non-coplanar setup were relatively greater than that of X-axis since a tilted head tended to slip down. The mean of X-axis movement of the group who used a mouthpiece was greater by 9.4% than the group who did not use, but the mean of Y-axis movement was lower by at least 64%, and the mean of Z-axis was lower by at least 67%, and the mean of Z-axis was lower by at least 67%, and the vector was lower by at least 59% with the use of a mouthpiece. Among these 8 patients, one patient whose tumor was located on left frontal lobe and left basal ganglia received reduced radiation dose of 38% in right eye, 23% in left eye, 30% in optic chiasm, 27% in brain stem, and 8% in normal brain with non-coplanar method. Conclusion: Tomotherapy only allows coplanar delivery of IMRT treatment. To complement this shortcoming, Tomotherapy can be used with non-coplanar method by artificially tilting the patient's head and using an oral immobilization instrument to minimize the movement of patient, when intracranial tumor locates near critical organs or has to be treated with high dose radiation.

  • PDF

Lung Injury Indices Depending on Tumor Necrosis Factor-$\alpha$ Level and Novel 35 kDa Protein Synthesis in Lipopolysaccharide-Treated Rat (내독소처치 흰쥐에서 Tumor Necrosis Factor-$\alpha$치 상승에 따른 폐손상 악화 및 35 kDa 단백질 합성)

  • Choi, Young-Mee;Kim, Young-Kyoon;Kwon, Soon-Seog;Kim, Kwan-Hyoung;Moon, Hwa-Sik;Song, Jeong-Sup;Park, Sung-Hak
    • Tuberculosis and Respiratory Diseases
    • /
    • v.45 no.6
    • /
    • pp.1236-1251
    • /
    • 1998
  • Background : TNF-$\alpha$ appears to be a central mediator of the host response to sepsis. While TNF-$\alpha$ is mainly considered a proinflammatory cytokine, it can also act as a direct cytotoxic cytokine. However, there are not so many studies about the relationship bet ween TNF-$\alpha$ level and lung injury severity in ALI, particularly regarding the case of ALI caused by direct lung injury such as diffuse pulmonary infection. Recently, a natural defense mechanism, known as the stress response or the heat shock response, has been reported in cellular or tissue injury reaction. There are a number of reports examining the protective role of pre-induced heat stress proteins on subsequent LPS-induced TNF-$\alpha$ release from monocyte or macrophage and also on subsequent LPS-induced ALI in animals. However it is not well established whether the stress protein synthesis such as HSP can be induced from rat alveolar macrophages by in vitro or in vivo LPS stimulation. Methods : We measured the level of TNF-$\alpha$, the percentage of inflammatory cells in bronchoalveolar lavage fluid, protein synthesis in alveolar macrophages isolated from rats at 1, 2, 3, 4, 6, 12, and 24 hours after intratracheal LPS instillation. We performed histologic examination and also obtained histologic lung injury index score in lungs from other rats at 1, 2, 3, 4, 6, 12, 24 h after intratracheal LPS instillation. Isolated non-stimulated macrophages were incubated for 2 h with different concentration of LPS (0, 1, 10, 100 ng/ml, 1, or 10 ${\mu}g/ml$). Other non-stimulated macrophages were exposed at $43^{\circ}C$ for 15 min, then returned to at $37^{\circ}C$ in 5% CO2-95% for 1 hour, and then incubated for 2 h with LPS (0, 1, 10, 100ng/ml, 1, or 10 ${\mu}g/ml$). Results : TNF-$\alpha$ levels began to increase significantly at 1 h, reached a peak at 3 h (P<0.0001), began to decrease at 6 h, and returned to control level at 12 h after LPS instillation. The percentage of inflammatory cells (neutrophils and alveolar macrophages) began to change significantly at 2 h, reached a peak at 6 h, began to recover but still showed significant change at 12 h, and showed insignificant change at 24 h after LPS instillation compared with the normal control. After LPS instillation, the score of histologic lung injury index reached a maximum value at 6 h and remained steady for 24 hours. 35 kDa protein band was newly synthesized in alveolar macrophage from 1 hour on for 24 hours after LPS instillation. Inducible heat stress protein 72 was not found in any alveolar macrophages obtained from rats after LPS instillation. TNF-$\alpha$ levels in supernatants of LPS-stimulated macro phages were significantly higher than those of non-stimulated macrophages(p<0.05). Following LPS stimulation, TNF-$\alpha$ levels in supernatants were significantly lower after heat treatment than in those without heat treatment (p<0.05). The inducible heat stress protein 72 was not found at any concentrations of LPS stimulation. Whereas the 35 kDa protein band was exclusively found at dose of LPS of 10 ${\mu}g/ml$. Conclusion : TNF-$\alpha$ has a direct or indirect close relationship with lung injury severity in acute lung injury or acute respiratory distress syndrome. In vivo and in vitro LPS stimulation dose not induce heat stress protein 72 in alveolar macrophages. It is likely that 35 kDa protein, synthesized by alveolar macrophage after LPS instillation, does not have a defense role in acute lung injury.

  • PDF

Clinical Application Analysis of 3D-CRT Methods Using Tomotherapy (토모테라피를 이용한 3차원 입체 조형 치료의 임상적 적용 분석)

  • Cho, Kang-Chul;Kim, Joo-Ho;Kim, Hun-Kyum;Ahn, Seung-Kwon;Lee, Sang-Kyoo;Yoon, Jong-Won;Cho, Jeong-Hee;Lee, Jong-Seok;Yoo, Beong-Gyu
    • Journal of radiological science and technology
    • /
    • v.36 no.4
    • /
    • pp.327-335
    • /
    • 2013
  • This study investigates the case of clinical application for TomoDirect 3D-CRT(TD-3D) and TomoHelical 3D-CRT(TH-3D) with evaluating dose distribution for clinical application in each case. Treatment plans were created for 8 patients who had 3 dimensional conformal radiation therapy using TD-3D and TH-3D mode. Each patients were treated for sarcoma, CSI(craniospinal irradiaion), breast, brain, pancreas, spine metastasis, SVC syndrome and esophagus. DVH(dose volume histogram) and isodose curve were used for comparison of each treatment modality. TD-3D shows better dose distribution over the irradiation field without junction effect because TD-3D was not influenced by target length for sarcoma and CSI case. In breast case, dosimetric results of CTV, the average value of D 99%, D 95% were $49.2{\pm}0.4$ Gy, $49.9{\pm}0.4$ Gy and V 105%, V 110% were 0%, respectively. TH-3D with the dosimetric block decreased dose of normal organ in brain, pancreas, spine metastasis case. SCV syndrome also effectively decreased dose of normal organ by using dose block to the critical organs(spinal cord <38 Gy). TH-3D combined with other treatment modalities was possible to boost irradiation and was total dose was reduced to spinal cord in esophagus case(spinal cord <45 Gy, lung V 20 <20%). 3D-CRT using Tomotherapy could overcomes some dosimetric limitations, when we faced Conventional Linac based CRT and shows clinically proper dose distribution. In conclusion, 3D-CRT using Tomotherapy will be one of the effective 3D-CRT techniques.

Analysis of domain required for aggregates formation of ALS (Amyotrophic lateral sclerosis)/FTD (Frontotemporal dementia)-linked FUS in mammalian cells (루게릭병 및 전측두엽성 치매 연관 단백질 Fused in Sarcoma (FUS)의 스트레스 응집체 형성에 관여하는 도메인 분석)

  • Jun, Mi-Hee;Lee, Jin-A
    • Analytical Science and Technology
    • /
    • v.28 no.5
    • /
    • pp.331-340
    • /
    • 2015
  • Mutations in Fused in Sarcoma (FUS) have been identified in patients with amyotrophic lateral sclerosis (ALS) or Frontotemporal Dementia (FTD). Pathological FUS is mis-localized to cytosol and forms aggregates associated with stress granules (SG), while FUS is normally localized to nucleus. However, it is largely unknown how pathological FUS forms SG-aggregates and which domains are responsible for this process. In this study, we examined cellular localization and aggregation of ALS-linked FUS missense mutants (P525L, R521C, R521H, R521G), analyzed the domains responsible for cytosolic FUS aggregation in HEK293T cells, and confirmed this in cultured mouse neurons. To do this, we firstly generated missense mutants of FUS and then examined their cellular localization. We found that P525L was mostly mis-localized to cytosol and formed FUS-positive SG aggregates while R521C, R521H, or R521G was localized to both nucleus and cytosol. To further characterize the domains required for aggregate formation of cytosolic FUS, we generated different domain-deletion mutants using FUS-∆17 which has a deletion of nuclear localization signal. Interestingly, cytosolic FUS without SYGQ and RGG1 domain or cytosolic FUS without RGG2-ZnF-RGG3 domain did not form FUS-positive SG aggregates, while cytosolic FUS without RRM domain generated more aggregates compared to FUS-∆17. Taken together, these data suggest that SYGQ-RGG1 or RGG2-ZnF-RGG3 domain contributes to formation of cytosolic aggregate, while RRM domain might interfere with FUS aggregation. Therefore, our studies will provide important insight for understanding cellular pathogenesis of neurodegeneration associated with FUS aggregate as well as finding therapeutic targets for ALS or FTD.

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
    • /
    • v.45 no.4
    • /
    • pp.439-448
    • /
    • 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.

Leukoencephalopathy after CNS Prophylactic Therapy in Pediatric Hematologic Malignancy (소아 혈액종양 환자에서 중추신경계 예방적 치료 후 발생한 백질뇌병증)

  • Lee, Jun Hwa;Lee, Sun Min;Choi, Eun Jin;Lee, Kun Soo
    • Clinical and Experimental Pediatrics
    • /
    • v.46 no.6
    • /
    • pp.566-571
    • /
    • 2003
  • Purpose : Leukoencephalopathy(LE) is one of the most serious complications in children with hematologic malignancies during the course of treatment. Early recognition is important to reduce the impact and sequelae from LE. We therefore investigated the clinical features of LE following central nervous system(CNS) prophylaxis in children with hematologic malignancies and evaluated the significance of regular check-ups of brain MRI. Methods : We retrospectively reviewed children with hematologic malignancies who had CNS prophylaxis including intrathecal(IT) methotrexate(MTX) and/or cranial irradiation at the Department of Pediatrics, Kyungpook National University Hospital from Oct. 1995 to May 2002. Fifteen cases of acute leukemia and one case of lymphoma who experienced LE following CNS prophylaxis were included in the study. Clinical data were analyzed from the medical records and brain MRIs were reviewed by neuroradiologists. Results : The ages ranged from 1 to 13 years(median age=5.2 years), and the male to female ratio was 3 : 1. The time interval from the beginning of chemotherapy to the time of diagnosis of LE ranged from 2 to 17 months. They all had IT MTX two to 15 times and ten underwent cranial irradiation(1,800 rads). At the time of diagnosis, ten of them had neuropsychiatric symptoms including seizures, personality changes, headache, etc. After the change of treatment modality, four cases showed significant improvement on follow-up MRIs, six cases had no significant changes and two had worsening of LE. Four patients died of infection and bone marrow relapse. Conclusion : CNS prophylaxis with IT therapy and cranial irradiation may cause leukoencephalopathy during the course of treatment. As a result, regular brain MRI check-up is recommended for the early detection and reducing the incidence of LE, along with changes in the treatment modality.