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대한내분비학회> Endocrinology and Metabolism(구 대한내분비학회지)> 증례 : kLight chain disease 에 대한 Fanconi`s syndrome 에서 골연화증과 사구체 족세포의 족돌기 소실을 보인 1 예

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증례 : kLight chain disease 에 대한 Fanconi`s syndrome 에서 골연화증과 사구체 족세포의 족돌기 소실을 보인 1 예

Case Reports : A Case of Adult Fanconi`s Syndrome with Glomerular Podocyte Foot Process Effacement and osteomalacia Induced by kLight Chain Disease

남재현(Jae Hyun Nam) , 최규헌(Gyu Hyun Choi) , 박기현(Ki Hyun Park) , 안철우(Chul Woo Ahn) , 송영득(Young Duk Song) , 임승길(Sung Kil Lim) , 이현철(Hyun Chul Lee) , 허갑범(Kap Bum Huh)
  • : 대한내분비학회
  • : Endocrinology and Metabolism(구 대한내분비학회지) 15권4호
  • : 연속간행물
  • : 2000년 12월
  • : 627-633(7pages)
Endocrinology and Metabolism(구 대한내분비학회지)

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The Fanconi`s syndrome is characterized by generalized disturbance of proximal tubular function. It leads to excessive losses of amino acids, glucose, phosphate, bicarbonate, and other substrates handled by the proximal tubules. The metabolic consequences are acidosis, hypophosphatemia, hypocalcemia, osteomalacia, osteoporosis, and growth retardation. Adult Fanconi`s syndrome is mostly secondary form caused by multiple myeloma, primary amyloidosis, light chain nephropathy, and heavy metal poisoning. We experienced 50-year-old woman with r light chain disease whose chief complaints were weakness of both lower extremities and multiple bone pain. This patient had renal glycosuria, hypercalciuria, normal anion gap type metabolic acidosis, osteomalacia and normal distal tubule acidification. Her bone marrow biopsy showed inappropriate proliferation of plasma cell. The patient underwent percutaneous renal biopsy in which was exceptionally observed focal effacement of podocyte foot process. So we report a case of osteomalacia caused by adult Fanconi`s syndrome and foot process effacement by κ-light chain disease (J Kor Soc Endocrinol 15:627-633, 2000).

UCI(KEPA)

I410-ECN-0102-2009-510-005279099

간행물정보

  • : 의약학분야  > 내과학
  • : KCI등재
  • : SCOPUS
  • : 격월
  • : 2093-596X
  • : 2093-5978
  • : 학술지
  • : 연속간행물
  • : 1986-2022
  • : 2658


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1Update from the 2022 World Health Organization Classification of Thyroid Tumors: A Standardized Diagnostic Approach

저자 : Chan Kwon Jung , Andrey Bychkov , Kennichi Kakudo

발행기관 : 대한내분비학회 간행물 : Endocrinology and Metabolism(구 대한내분비학회지) 37권 5호 발행 연도 : 2022 페이지 : pp. 703-718 (16 pages)

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The fifth edition of the World Health Organization (WHO) histologic classification of thyroid neoplasms released in 2022 includes newly recognized tumor types, subtypes, and a grading system. Follicular cell-derived neoplasms are categorized into three families (classes): benign tumors, low-risk neoplasms, and malignant neoplasms. The terms “follicular nodular disease” and “differentiated high-grade thyroid carcinoma” are introduced to account for multifocal hyperplastic/neoplastic lesions and differentiated thyroid carcinomas with high-grade features, respectively. The term “Hürthle cells” is replaced with “oncocytic cells.” Invasive encapsulated follicular and cribriform morular variants of papillary thyroid carcinoma (PTC) are now redefined as distinct tumor types, given their different genetic alterations and clinicopathologic characteristics from other PTC subtypes. The term “variant” to describe a subclass of tumor has been replaced with the term “subtype.” Instead, the term “variant” is reserved to describe genetic alterations. A histologic grading system based on the mitotic count, necrosis, and/or the Ki67 index is used to identify high-grade follicular-cell derived carcinomas and medullary thyroid carcinomas. The 2022 WHO classification introduces the following new categories: “salivary gland-type carcinomas of the thyroid” and “thyroid tumors of uncertain histogenesis.” This review summarizes the major changes in the 2022 WHO classification and their clinical relevance.

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2Independent Skeletal Actions of Pituitary Hormones

저자 : Se-min Kim , Farhath Sultana , Funda Korkmaz , Daria Lizneva , Tony Yuen , Mone Zaidi

발행기관 : 대한내분비학회 간행물 : Endocrinology and Metabolism(구 대한내분비학회지) 37권 5호 발행 연도 : 2022 페이지 : pp. 719-731 (13 pages)

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Over the past years, pituitary hormones and their receptors have been shown to have non-traditional actions that allow them to bypass the hypothalamus-pituitary-effector glands axis. Bone cells―osteoblasts and osteoclasts―express receptors for growth hormone, follicle stimulating hormone (FSH), thyroid stimulating hormone (TSH), adrenocorticotrophic hormone (ACTH), prolactin, oxytocin, and vasopressin. Independent skeletal actions of pituitary hormones on bone have been studied using genetically modified mice with haploinsufficiency and by activating or inactivating the receptors pharmacologically, without altering systemic effector hormone levels. On another front, the discovery of a TSH variant (TSH-βv) in immune cells in the bone marrow and skeletal action of FSHβ through tumor necrosis factor α provides new insights underscoring the integrated physiology of bone-immune-endocrine axis. Here we discuss the interaction of each pituitary hormone with bone and the potential it holds in understanding bone physiology and as a therapeutic target.

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3Updates on Paget's Disease of Bone

저자 : Yong Jun Choi , Young Bae Sohn , Yoon-sok Chung

발행기관 : 대한내분비학회 간행물 : Endocrinology and Metabolism(구 대한내분비학회지) 37권 5호 발행 연도 : 2022 페이지 : pp. 732-743 (12 pages)

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Paget's disease of the bone is a prevalent bone disease characterized by disorganized bone remodeling; however, it is comparatively uncommon in East Asian countries, including China, Japan, and Korea. The exact cause still remains unknown. In genetically susceptible individuals, environmental triggers such as paramyxoviral infections are likely to cause the disease. Increased osteoclast activity results in increased bone resorption, which attracts osteoblasts and generates new bone matrix. Fast bone resorption and formation lead to the development of disorganized bone tissue. Increasing serum alkaline phosphatase or unique radiographic lesions may serve as the diagnostic indicators. Common symptoms include bone pain, bowing of the long bones, an enlarged skull, and hearing loss. The diagnosis is frequently confirmed by radiographic and nuclear scintigraphy of the bone. Further, bisphosphonates such as zoledronic acid and pamidronate are effective for its treatment. Moreover, biochemical monitoring is superior to the symptoms as a recurrence indicator. This article discusses the updates of Paget's disease of bone with a clinical case.

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4Update on Preoperative Parathyroid Localization in Primary Hyperparathyroidism

저자 : Hye-sun Park , Namki Hong , Jong Ju Jeong , Mijin Yun , Yumie Rhee

발행기관 : 대한내분비학회 간행물 : Endocrinology and Metabolism(구 대한내분비학회지) 37권 5호 발행 연도 : 2022 페이지 : pp. 744-755 (12 pages)

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Parathyroidectomy is the treatment of choice for primary hyperparathyroidism when the clinical criteria are met. Although bilateral neck exploration is traditionally the standard method for surgery, minimally invasive parathyroidectomy (MIP), or focused parathyroidectomy, has been widely accepted with comparable curative outcomes. For successful MIP, accurate preoperative localization of parathyroid lesions is essential. However, no consensus exists on the optimal approach for localization. Currently, ultrasonography and technetium-99m-sestamibi-single photon emission computed tomography/computed tomography are widely accepted in most cases. However, exact localization cannot always be achieved, especially in cases with multiglandular disease, ectopic glands, recurrent disease, and normocalcemic primary hyperparathyroidism. Therefore, new modalities for preoperative localization have been developed and evaluated. Positron emission tomography/computed tomography and parathyroid venous sampling have demonstrated improvements in sensitivity and accuracy. Both anatomical and functional information can be obtained by combining these methods. As each approach has its advantages and disadvantages, the localization study should be deliberately chosen based on each patient's clinical profile, costs, radiation exposure, and the availability of experienced experts. In this review, we summarize various methods for the localization of hyperfunctioning parathyroid tissues in primary hyperparathyroidism.

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5You Can't Avoid Shift Work? Then Focus on Body Fat Rather than Weight

저자 : Eun Kyung Lee

발행기관 : 대한내분비학회 간행물 : Endocrinology and Metabolism(구 대한내분비학회지) 37권 5호 발행 연도 : 2022 페이지 : pp. 756-758 (3 pages)

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6Association between the Diabetes Drug Cost and Cardiovascular Events and Death in Korea: A National Health Insurance Service Database Analysis

저자 : Seung Min Chung , Ji-in Lee , Eugene Han , Hyun-ae Seo , Eonju Jeon , Hye Soon Kim , Ji Sung Yoon

발행기관 : 대한내분비학회 간행물 : Endocrinology and Metabolism(구 대한내분비학회지) 37권 5호 발행 연도 : 2022 페이지 : pp. 759-769 (11 pages)

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Background: This study aimed to investigate the long-term effects of diabetes drug costs on cardiovascular (CV) events and death.
Methods: This retrospective observational study used data from 2009 to 2018 from the National Health Insurance in Korea. Among the patients with type 2 diabetes, those taking antidiabetic drugs and who did not have CV events until 2009 were included. Patients were divided into quartiles (Q1 [lowest]-4 [highest]) according to the 2009 diabetes drug cost. In addition, the 10-year incidences of CV events (non-fatal myocardial infarction, stroke, hospitalization for heart failure, and coronary revascularization) and CV death (death due to CV events) were analyzed.
Results: A total of 441,914 participants were enrolled (median age, 60 years; men, 57%). CV events and death occurred in 28.1% and 8.36% of the patients, respectively. The 10-year incidences of CV events and deaths increased from Q1 to 4. After adjusting for sex, age, income, type of diabetes drugs, comorbidities, and smoking and drinking status, the risk of CV events significantly increased according to the sequential order of the cost quartiles. In contrast, the risk of CV death showed a U-shaped pattern, which was the lowest in Q3 (hazard ratio [HR], 0.953; 95% confidence interval [CI], 0.913 to 0.995) and the highest in Q4 (HR, 1.266; 95% CI, 1.213 to 1.321).
Conclusion: Diabetes drug expenditure affects 10-year CV events and mortality. Therefore, affording an appropriate diabetes drug cost at a similar risk of CV is an independent protective factor against CV death.

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7Association among Current Smoking, Alcohol Consumption, Regular Exercise, and Lower Extremity Amputation in Patients with Diabetic Foot: Nationwide Population-Based Study

저자 : Yoon Jae Lee , Kyung-do Han , Jun Hyeok Kim

발행기관 : 대한내분비학회 간행물 : Endocrinology and Metabolism(구 대한내분비학회지) 37권 5호 발행 연도 : 2022 페이지 : pp. 770-780 (11 pages)

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Background: The present study investigates whether modifiable behavioral factors of current cigarette smoking, heavy alcohol consumption, and regular exercise are associated with risk of lower extremity amputation (LEA) in diabetic patients.
Methods: A total of 2,644,440 diabetic patients (aged ≥20 years) was analyzed using the database of the Korean National Health Insurance Service. Cox proportional hazard regression was used to assess adjusted hazard ratios (HRs) for the behavioral factors with risk of LEA under adjustment for potential confounders.
Results: The risk of LEA was significantly increased by current cigarette smoking and heavy alcohol consumption (HR, 1.436; 95% confidence interval [CI], 1.367 to 1.508 and HR, 1.082; 95% CI, 1.011 to 1.158) but significantly decreased with regular exercise (HR, 0.745; 95% CI, 0.706 to 0.786) after adjusting for age, sex, smoking, alcohol consumption, exercise, low income, hypertension, dyslipidemia, body mass index, using insulin or oral antidiabetic drugs, and diabetic duration. A synergistically increased risk of LEA was observed with larger number of risky behaviors.
Conclusion: Modification of behaviors of current smoking, heavy alcohol intake, and exercise prevents LEA and can improve physical, emotional, and social quality of life in diabetic patients.

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8Association of Shift Work with Normal-Weight Obesity in Community-Dwelling Adults

저자 : Chul Woo Ahn , Sungjae Shin , Seunghyun Lee , Hye-sun Park , Namki Hong , Yumie Rhee

발행기관 : 대한내분비학회 간행물 : Endocrinology and Metabolism(구 대한내분비학회지) 37권 5호 발행 연도 : 2022 페이지 : pp. 781-790 (10 pages)

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Background: Shift work is associated with obesity and metabolic syndrome. However, this association in the normal-weight population remains unclear. This study aimed to investigate whether shift work is associated with normal-weight obesity (NWO).
Methods: From the nationally representative Korea National Health and Nutrition Examination Survey (KNHANES) dataset (2008 to 2011), 3,800 full-time workers aged ≥19 years with a body mass index (BMI) ≤25 kg/m2 were analysed. We defined NWO as BMI ≤25 kg/m2 and body fat percentage ≥25% in men and ≥37% in women. Working patterns were classified into “daytime,” “other than daytime,” and “shift.” Multivariable logistic regression analysis was performed to evaluate the relationship between shift work and NWO.
Results: Shift work was associated with higher odds of NWO than daytime work (adjusted odds ratio [aOR], 1.47; 95% confidence interval [CI], 1.04 to 2.09) and night/evening work (aOR, 1.87; 95% CI, 1.11 to 3.14) after adjustment for type of work, working hours, age, sex, BMI, 25-hydroxyvitamin D levels, homeostatic model assessment for insulin resistance, and other sociodemographic factors. In subgroup analyses, the association between shift work and NWO was more robust in those aged ≥60 years and those working ≥56 hours/week.
Conclusion: Shift work was associated with NWO in community-dwelling Korean adults, independent of age, sex, BMI, and other covariates.

KCI등재 SCOPUS

9Recent Changes in the Incidence of Thyroid Cancer in Korea between 2005 and 2018: Analysis of Korean National Data

저자 : Yun Mi Choi , Jiwoo Lee , Mi Kyung Kwak , Min Ji Jeon , Tae Yong Kim , Eun-gyoung Hong , Won Bae Kim , Won Gu Kim

발행기관 : 대한내분비학회 간행물 : Endocrinology and Metabolism(구 대한내분비학회지) 37권 5호 발행 연도 : 2022 페이지 : pp. 791-799 (9 pages)

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Background: In this study, we evaluated the recent changes in the standardized, age-specific, stage-specific incidence rates (IRs) of thyroid cancer in Korea and compared them with the incidence data reported by the Surveillance, Epidemiology, and End Results Program.
Methods: The analysis was conducted using the incidence data (2005 to 2018) from the Statistics Korea and Korea Central Cancer Registry.
Results: The age-standardized IR (SIR) of thyroid cancer increased from 24.09 per 100,000 in 2005 to 74.83 in 2012 (annual percent change [APC], 14.5). From 2012 to 2015, the SIR decreased to 42.52 (APC, -17.9) and then remained stable until 2018 (APC, 2.1). This trend was similar in both men and women. Regarding age-specific IRs, the IRs for ages of 30 years and older showed a trend similar to that of the SIR; however, for ages below 30 years, no significant reduction was observed from the vertex of IR in 2015. Regarding stage-specific IRs, the increase was more prominent in those with regional disease (APC, 17.4) than in those with localized disease until 2012; then, the IR decreased until 2015 (APC, -16.1). The average APC from 2005 to 2018 increased in men, those under the age of 30 years, and those with regional disease.
Conclusion: The SIR in Korea peaked in 2012 and decreased until 2015 and then remained stable until 2018. However, in young individuals under the age of 30 years, the IR did not significantly decrease but tended to increase again. In terms of stage-specific IRs, the sharpest increase was seen among those with regional disease.

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10DN200434 Inhibits Vascular Smooth Muscle Cell Proliferation and Prevents Neointima Formation in Mice after Carotid Artery Ligation

저자 : Sudeep Kumar , Jonghwa Jin , Hyeon Young Park , Mi-jin Kim , Jungwook Chin , Sungwoo Lee , Jina Kim , Jung-guk Kim , Yeon-kyung Choi , Keun-gyu Park

발행기관 : 대한내분비학회 간행물 : Endocrinology and Metabolism(구 대한내분비학회지) 37권 5호 발행 연도 : 2022 페이지 : pp. 800-809 (10 pages)

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Background: Excessive proliferation and migration of vascular smooth muscle cells (VSMCs), which contributes to the development of occlusive vascular diseases, requires elevated mitochondrial oxidative phosphorylation to meet the increased requirements for energy and anabolic precursors. Therefore, therapeutic strategies based on blockade of mitochondrial oxidative phosphorylation are considered promising for treatment of occlusive vascular diseases. Here, we investigated whether DN200434, an orally available estrogen receptor-related gamma inverse agonist, inhibits proliferation and migration of VSMCs and neointima formation by suppressing mitochondrial oxidative phosphorylation.
Methods: VSMCs were isolated from the thoracic aortas of 4-week-old Sprague-Dawley rats. Oxidative phosphorylation and the cell cycle were analyzed in fetal bovine serum (FBS)- or platelet-derived growth factor (PDGF)-stimulated VSMCs using a Seahorse XF-24 analyzer and flow cytometry, respectively. A model of neointimal hyperplasia was generated by ligating the left common carotid artery in male C57BL/6J mice.
Results: DN200434 inhibited mitochondrial respiration and mammalian target of rapamycin complex 1 activity and consequently suppressed FBS- or PDGF-stimulated proliferation and migration of VSMCs and cell cycle progression. Furthermore, DN200434 reduced carotid artery ligation-induced neointima formation in mice.
Conclusion: Our data suggest that DN200434 is a therapeutic option to prevent the progression of atherosclerosis.

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5포도당과 이소프로테레놀에 의한 시상하부의 소마토스타틴 분비가 갑상선자극호르몬방출호르몬에 의한 갑상선자극호르몬에 미치는 효과

저자 : 박철영(Cheol Young Park) , 양인명(In Myung Yang) , 오승준(Seung Joon Oh) , 김덕윤(Deog Yoon Kim) , 우정택(Jeong Taek Woo) , 김성운(Sung Woon Kim) , 김진우(Jin Woo Kim) , 김영설(Young Seol Kim) , 최영길(Young Kil Choi)

발행기관 : 대한내분비학회 간행물 : Endocrinology and Metabolism(구 대한내분비학회지) 15권 4호 발행 연도 : 2000 페이지 : pp. 486-492 (7 pages)

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Background: Acute hyperglycemia stimulates somatostatin (SRIH) release from the hypothalamus, and which in turn suppress growth hormone (GH) secretion and thyroid stimulating hormone (TSH) from the anterior pituitary gland. Beta-adrenergic pathway is known to stimulate the hypothalamus SRIH release. Recently, We demonstrated that isoproterenol, a beta-adrenergic agonist, had an additional suppressive effect on the suppression by glucose of GHRH-stimulated GH response. Therefore, the present study aimed to determine whether isoproterenol has an additional suppressive effect on the suppression by glucose of TRH-stimulated TSH response. Methods: Seven healthy young men, aged 24 to 27 years, were studied. Four different TRH stimulation tests were carried out. (Test 1) TRH (Hoechst AG, Germany), 200 μg bolus, was given intravenously at 0 minute. (Test 2) Glucose, 100 g, was given orally 30 min before TRH administration. (Test 3) Isoproterenol(Isuprel, Sanofi Winthrop, USA), 0.012 pg/kg, was infused continuously for 120 min after TRH administration. (Test 4) After pretreatment with glucose as Test 2, isoproterenol and TRH were administered as Test 3. Results: Oral glucose ingestion significantly suppressed the TRH-stimulated TSH secretion. Isoproterenol infusion significantly suppressed the TRH-stimulated TSH secretion. Glucose-induced suppression of the TSH response was significantly greater than that by isoproterenol. 1soproterenol infusion after glucose pretreatment did not show any additional suppressive effect on the glucose-induced suppression of TSH response to TRH. Conclusion: The results suggest that isoproterenol infusion in addition to glucose pretreatment before the TRH stimulation test is not necessary for the development of stronger stimulation test for the hypothalamic somatostatin secretion (J Kor Soc Endocrinol l5:486-492, 2000).

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6성장호르몬 결핍증 환아에서 성장호르몬 치료가 혈청 leptin 농도에 미치는 영향

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발행기관 : 대한내분비학회 간행물 : Endocrinology and Metabolism(구 대한내분비학회지) 15권 4호 발행 연도 : 2000 페이지 : pp. 493-501 (9 pages)

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Background: Leptin the ob gene product is secreted by adipocytes and binds to specific receptors in the central nervous system regulating energe intake and expenditure. Correlation between fat mass and leptin level is well established. However, data on the hormonal regulation of the leptin in human are scarce. Growth hormone (GH) has lypolytic action and patients with growth hormone deficiency (GHD) have showed higher leptin levels than expected for the obesity We investigated the changes in serum leptin levels and body mass index in children with GHD during GH therapy. Methods: Thirty children with GHD participated. All subjects were 5~13 years old and in prepubertal stage. The causes of GHD were idiopathic in 15 and organic in 15 children. Patients received GH 0.6.7 IU/kg/week subcutaneously, in 67 divided doses and investigated at baseline and after 6 and 12 months of GH treatment. Serum leptin levels were determined with a human leptin and IGF-1 radioimmunoassay (Linco Research and Nichols Institute, USA). Results: The height velocity was increased significantly after 12 months of GH treatment. Serum leptin concentrations were significantly reduced after 6 and 12 months of treatment but revealed no significant differences in the sex and the causes of GHD. Body mass indices were significantly reduced after treatment. Serum leptin levels positively correlated with body mass index at baseline and after 6 and 12 months of GH treatment. The serum IGF-1 level were increased significantly after GH treatment and did not significantly correlated with leptin levels at baseline and after treatment. Conclusion: This study demonstrated that serum leptin and body mass index were decreased with significant positive correlation during GH treatment in children with GHD (J Kor Soc Endocrinol 15:493-501, 2000).

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7유전성 비만 마우스 ( ob / ob ) 에서 Retrovirus 를 이용한 Leptin 유전자의 전입 및 발현

저자 : 변용준(Young Jun Byun) , 정인철(In Cheol Jeong) , 오상환(Sang Hwan Oh) , 조무연(Moo Youn Cho)

발행기관 : 대한내분비학회 간행물 : Endocrinology and Metabolism(구 대한내분비학회지) 15권 4호 발행 연도 : 2000 페이지 : pp. 502-512 (11 pages)

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Background: Leptin gene is known to be related to obesity in human and animals and complete genetic defect of the gene in ob/ob mouse has been identified. Therefore, ob/ob mouse is widely used as an animal model for the study of etiology and therapy of obesity. The main biological function of leptin was thought to involve in the regulation of food intake and weight gain, however, the regulatory mechanisms by which leptin functions in the weight reduction and lowering the blood glucose level are uncertain. In the present study, retroviral-mediated leptin gene transduction into ob/ob mouse was attempted for the correction of biochemical parameters of obesity. Methods: Leptin cDNA was inserted into pLXSN retroviral vector (pLXSN-lep) and recombinant leptin expressing retrovirus particles (3 X10 CFU/mL) were produced in Ψ2 ecotropic packaging cells and subsequent transfection into PA317 amphotropic packaging cells. The leptin expressing recombinant viruses (LER) were transduced into NIH3T3 mouse fibroblasts and insertion of leptin cDNA into chromosomal DNA of PA317 and MH3T3 mouse fibroblasts was confirmed by Southern blot hybridizations. Leptin mRNA and its protein expressed in the cells were identified by Northern blot hybridization and Western blot immunodetection method, respectively. LER were injected I. P. into ob/ob mice, and body weight, food intake, serum leptin level and blood glucose level were measured. Results: Expression of leptin was identified in PA317 and NIH3T3 mouse fibroblasts transduced with LER. Leptin content in sera of mice transfused with LER was drastically increased after 1 week and decreased to the almost basal level at 3 weeks after the transfusion. The body weight as well as food intake of ob/ob mouse transduced by LER decreased for the first 3 weeks and slightly increased thereafter. The reduction of both body weight and food intake in ob/ob mice transduced with LER was observed with the concomitant increase of serum leptin level, indicating that retroviral-mediated transduction of leptin gene in ob/ob mouse in vivo produced a biologically active leptin protein and released it into blood circulation. Conclusion: A transient expression of leptin cDNA in ob/ob mice by a retroviral-mediated transduction was performed and further studies are required for long term expression of the gene in vivo (J Kor Soc Endocrinol 15:502-512, 2000).

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8갑상선 여포선암 진단시 HBME - 1 면역염색법의 유용성

저자 : 신영구(Young Goo Shin) , 이기범(Kyi Bum Lee) , 정윤석(Yoon Sok Chung) , 김현만(Hyeon Man Kim)

발행기관 : 대한내분비학회 간행물 : Endocrinology and Metabolism(구 대한내분비학회지) 15권 4호 발행 연도 : 2000 페이지 : pp. 513-521 (9 pages)

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Background: Leptin gene is known to be related to obesity in human and animals and complete genetic defect of the gene in ob/ob mouse has been identified. Therefore, ob/ob mouse is widely used as an animal model for the study of etiology and therapy of obesity. The main biological function of leptin was thought to involve in the regulation of food intake and weight gain, however, the regulatory mechanisms by which leptin functions in the weight reduction and lowering the blood glucose level are uncertain. In the present study, retroviral-mediated leptin gene transduction into ob/ob mouse was attempted for the correction of biochemical parameters of obesity. Methods: Leptin cDNA was inserted into pLXSN retroviral vector (pLXSN-lep) and recombinant leptin expressing retrovirus particles (3 X10 CFU/mL) were produced in Ψ2 ecotropic packaging cells and subsequent transfection into PA317 amphotropic packaging cells. The leptin expressing recombinant viruses (LER) were transduced into NIH3T3 mouse fibroblasts and insertion of leptin cDNA into chromosomal DNA of PA317 and MH3T3 mouse fibroblasts was confirmed by Southern blot hybridizations. Leptin mRNA and its protein expressed in the cells were identified by Northern blot hybridization and Westen blot immunodetection method, respectively. LER were injected I. P. into ob/ob mice, and body weight, food intake, serum leptin level and blood glucose level were measured. Results: Expression of leptin was identified in PA317 and NIH3T3 mouse fibroblasts transduced with LER. Leptin content in sera of mice transfused with LER was drastically increased after 1 week and decreased to the almost basal level at 3 weeks after the transfusion. The body weight as well as food intake of ob/ob mouse transduced by LER decreased for the first 3 weeks and slightly increased thereafter. The reduction of both body weight and food intake in ob/ob mice transduced with LER was observed with the concomitant increase of serum leptin level, indicating that retroviral-mediated transduction of leptin gene in ob/ob mouse in vivo produced a biologically active leptin protein and released it into blood circulation. Conclusion: A transient expression of leptin cDNA in ob/ob mice by a retroviral-mediated transduction was performed and further studies are required for long term expression of the gene in vivo (J Kor Soc Endocrinol 15:502-512, 2000).

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9갑상선암 세포주에서 아데노바이러스 - hNIS ( Ad - hNIS ) 유전자 이입에 의한 방사성 요오드 포획 증진 효과

저자 : 박건구(Kun Koo Park) , 진정선(Jung Sun Jin) , 이성진(Seong Jin Lee) , 박정윤(Jung Yoon Park) , 이희란(Heui Ran Lee) , 문대혁(Dae Hyuk Moon) , 안일민(Il Min Ahn) , 장혜숙(Hye Sook Chang)

발행기관 : 대한내분비학회 간행물 : Endocrinology and Metabolism(구 대한내분비학회지) 15권 4호 발행 연도 : 2000 페이지 : pp. 522-531 (10 pages)

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Background: The sodium-iodide-symporter (NIS) is a plasma membrane glycoprotein with 13 putative transmembrane domains, which is responsible for concentrating iodide into the thyroid by an active transport and provides the mechanism for radioactive-iodine (RAI) therapy for thyroid cancer. However, undifferentiated thyroid cancers and about 2050% of differentiated thyroid cancers do not take up the RAI at therapeutic dose. The NIS has been cloned from rat and human (hNIS) and characterized recently. In an attempt to develop a new therapeutic strategy using hNIS gene for improving the efficacy of RAI therapy in thyroid cancers, we have constructed a recombinant adenovirus encoding the hNIS (Ad-hNIS) and tested its function by an iodide uptake by infecting human thyroid cancer cells. Methods: RT-PCR was performed to measure an intrinsic hNIS expression in thyroid cancer cell lines, such as NPA, FRO and ARO. To generate the hNIS adenovirus, hNIS cDNA was isolated and ligated into Swa I site of cosmid shuttle vector (pAxCAwt). We have produced recombinant adenovirus by co-transfecting the cosmid with DNA-TPC to 293 cell line. Adenovirus that express (β-Galactosidase (LacZ) was also prepared by the similar strategy. Adenovirus infection efficiency was measured in three thyroid cancer cell lines. Finally, 24 hours after infection of ad-hNIS into the cells, I125-uptake was measured. Results: Endogenous hNIS expression was detected only in FRO cells but not in NPA, ARO and Hela cells by RT-PCR. X-Gal staining after infection of Ad-LacZ to thyroid cancer cell (NPA, ARO, FRO) showed that an infection rate in ARO cells was 98.5+0.5%, 97.0+0.2% in FRO cells and 75.5+5.0% in NPA cells. We selected ARO cells for the infection of Ad-hNIS due to the highest infection efficiency and the absence of endogenous hNIS expression. When ARO cells were infected with the ad-hNIS, I125 uptake was increased 504+6.4%. Conclusion: Overexpression of hNIS gene in thyroid cancer cells elicited over 5 fold increase in I-uptake, suggesting that the Ad-hNIS infection to the thyroid cancer cells may improve the efficiency of radioactive iodine therapy (J Kor Soc Endocrinol 15:522-53l, 2000).

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10양성 갑상선 결절에서 티록신 억제 요법의 효과

저자 : 윤석기(Seog Ki Yun) , 김철희(Chul Hee Kim) , 김영선(Young Sun Kim) , 변동원(Dong Won Byun) , 서교일(Kyo Il Suh) , 유명희(Myung Hi Yoo)

발행기관 : 대한내분비학회 간행물 : Endocrinology and Metabolism(구 대한내분비학회지) 15권 4호 발행 연도 : 2000 페이지 : pp. 532-541 (10 pages)

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Background: Benign pathologic findings are shown in 800% of thyroid nodules by fine needle aspiration cytology (FNAC) or needle biopsy. About half of these benign nodules are follicular lesions which are presented only as thyroid follicles or thyroid cell clumps. Differential diagnosis of follicular adenoma, follicular carcinoma and adenomatous goiter is impossible by FNAC or needle biopsy. Thyroxine suppression therapy has been performed traditionally in order to discriminate malignant nodules, but few studies are available which confirmed the efficacy of thyroxine suppression therapy in thyroid nodules of those the initial pathologic findings were follicular lesions. So we tried to evaluate the efficacy of thyroxine suppression therapy in benign thyroid nodules and also the incidence of thyroid cancer of the thyroid nosules which were not decreased on thyroxine suppression therapy after surgical resection. Methods: Total 1027 patients with thyroid nodules were evaluated by FNAC or needle biopsy at Soonchunhyang university hospital from 1990 to 1996. Among 1027 patients, 507 patients showed follicular lesions in FNAC or needle biopsy and they received thyroxine suppression therapy. Thyroid nodule volume was measured before and after thyroxine suppression therapy using ultrasonography. We studied 184 patients who were followed up for more than 1 year. Serial changes of thyroid function tests, thyroid nodule volume, serum thyroglubulin (Tg) level before and after therapy were analyzed. Results: l. In 80 (43.5%) of the 184 patients, nodule volumes decreased more than 50 percent after thyroxine suppression therapy. 2. There was no significant difference in serum T3, T4, TSH levels before and after thyroxine suppression therapy between group I (nodule volume decreased less than 50%) and group II (nodule volume decreased more than 50%). 3. In group II patients, thyroid nodule volumes were decreased continuously at 12 month, 18 month and 30 month after thyroxine suppression (p<0.05). 4. There was no significant difference between the group I and group II in the frequency of multiple thyroid nodules on ultrasonography. 5. Among 37 patients who underwent thyroidectomy, 19 cases (51.4%) were revealed as malignant thyroid nodules (papillary cancer 4 cases, follicular cancer 15 cases). Eighteen cases (48.6%) were revealed as benign thyroid nodules (follicular adenoma 10 cases, adenomatous goiter 8 cases). 6. There was no significant difference in the frequency of multiple nodules on ultrasonography between benign and malignant nodules. Conclusion: Our data suggested thyroxine suppression therapy was effective in discriminating malignant thyroid nodules from benign nodules, especially in selecting follicular carcinoma from follicular lesion by FNAC or biopsy (J Kor Soc Endocrinol 15:532-541, 2000).

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