1.Adenovirus-induced Reactive Astrogliosis Exacerbates the Pathology of Parkinson’s Disease
Heeyoung AN ; Hyowon LEE ; Seulkee YANG ; Woojin WON ; C. Justin LEE ; Min-Ho NAM
Experimental Neurobiology 2021;30(3):222-231
Parkinson’s disease (PD) is the most prevalent neurodegenerative motor disorder. While PD has been attributed to dopaminergic neuronal death in substantia nigra pars compacta (SNpc), accumulating lines of evidence have suggested that reactive astrogliosis is critically involved in PD pathology. These pathological changes are associated with α-synuclein aggregation, which is more prone to be induced by an A53T mutation. Therefore, the overexpression of A53T-mutated α-synuclein (A53T-α-syn) has been utilized as a popular animal model of PD. However, this animal model only shows marginal-to-moderate extents of reactive astrogliosis and astrocytic α-synuclein accumulation, while these phenomena are prominent in human PD brains. Here we show that Adeno-GFAP-GFP virus injection into SNpc causes severe reactive astrogliosis and exacerbates the A53Tα-syn-mediated PD pathology. In particular, we demonstrate that AAV-CMV-A53T-α-syn injection, when combined with Adeno-GFAP-GFP, causes more significant loss of dopaminergic neuronal tyrosine hydroxylase level and gain of astrocytic GFAP and GABA levels. Moreover, the combination of AAV-CMV-A53T-α-syn and Adeno-GFAP-GFP causes an extensive astrocytic α-syn expression, just as in human PD brains. These results are in marked contrast to previous reports that AAV-CMV-A53T-α-syn alone causes α-syn expression mostly in neurons but rarely in astrocytes. Furthermore, the combination causes a severe PD-like motor dysfunction as assessed by rotarod and cylinder tests within three weeks from the virus injection, whereas Adeno-GFAP-GFP alone or AAV-CMV-A53T-α-syn alone does not. Our findings implicate that inducing reactive astrogliosis exacerbates PD-like pathologies and propose the virus combination as an advanced strategy for developing a new animal model of PD.
2.Adenovirus-induced Reactive Astrogliosis Exacerbates the Pathology of Parkinson’s Disease
Heeyoung AN ; Hyowon LEE ; Seulkee YANG ; Woojin WON ; C. Justin LEE ; Min-Ho NAM
Experimental Neurobiology 2021;30(3):222-231
Parkinson’s disease (PD) is the most prevalent neurodegenerative motor disorder. While PD has been attributed to dopaminergic neuronal death in substantia nigra pars compacta (SNpc), accumulating lines of evidence have suggested that reactive astrogliosis is critically involved in PD pathology. These pathological changes are associated with α-synuclein aggregation, which is more prone to be induced by an A53T mutation. Therefore, the overexpression of A53T-mutated α-synuclein (A53T-α-syn) has been utilized as a popular animal model of PD. However, this animal model only shows marginal-to-moderate extents of reactive astrogliosis and astrocytic α-synuclein accumulation, while these phenomena are prominent in human PD brains. Here we show that Adeno-GFAP-GFP virus injection into SNpc causes severe reactive astrogliosis and exacerbates the A53Tα-syn-mediated PD pathology. In particular, we demonstrate that AAV-CMV-A53T-α-syn injection, when combined with Adeno-GFAP-GFP, causes more significant loss of dopaminergic neuronal tyrosine hydroxylase level and gain of astrocytic GFAP and GABA levels. Moreover, the combination of AAV-CMV-A53T-α-syn and Adeno-GFAP-GFP causes an extensive astrocytic α-syn expression, just as in human PD brains. These results are in marked contrast to previous reports that AAV-CMV-A53T-α-syn alone causes α-syn expression mostly in neurons but rarely in astrocytes. Furthermore, the combination causes a severe PD-like motor dysfunction as assessed by rotarod and cylinder tests within three weeks from the virus injection, whereas Adeno-GFAP-GFP alone or AAV-CMV-A53T-α-syn alone does not. Our findings implicate that inducing reactive astrogliosis exacerbates PD-like pathologies and propose the virus combination as an advanced strategy for developing a new animal model of PD.
3.In Vitro Adenosine Triphosphate Based Chemotherapy Response Assay in Gastric Cancer.
Seulkee PARK ; Yanghee WOO ; Hogeun KIM ; Yong Chan LEE ; Sungho CHOI ; Woo Jin HYUNG ; Sung Hoon NOH
Journal of Gastric Cancer 2010;10(4):155-161
PURPOSE: The purpose of this study was to investigate the reliability and the clinical applicability of the adenosine-triphosphate-based chemotherapy response assay (ATP-CRA) as a method of determining in vitro chemosensitivity in patients with gastric cancer. MATERIALS AND METHODS: A total of 243 gastric cancer tissue samples were obtained from gastrectomies performed between February 2007 and January 2010. We evaluated the effectiveness of the ATP-CRA assay in determining the chemosensitivity of gastric cancer specimens using eleven chemotherapeutic agents - etoposide, doxorubicin, epirubicin, mytomicin, 5-fluorouracil, oxaliplatin, irinotecan, docetaxel, paclitaxel, methotraxate, and cisplatin - for chemosensitivity studies using ATP-CRA. We assessed the failure rate, the cell death rate, and the chemosensitivity index. RESULTS: The failure rate of ATP-CRA was 1.6% (4/243). The mean coefficient of variation for triplicate ATP measurements was 6.5%. Etoposide showed the highest cell death rate (35.9%) while methotrexate showed the lowest (16.6%). The most active chemotherapeutic agent was etoposide, which most frequently ranked highest in the chemosensitivity test: 31.9% (51/160). Oxaliplatin was more active against early gastric cancers than advanced gastric cancers, whereas docetaxel was more active against advanced cancers. The lymph node negative group showed a significantly higher cell death rate than the lymph node positive group when treated with doxorubicin, epirubicin, and mitomycin. CONCLUSIONS: ATP-CRA is a stable and clinically applicable in vitro chemosensitivity test with a low failure rate. The clinical usefulness of ATP-CRA should be evaluated by prospective studies comparing the regimen guided by ATP-CRA with an empirical regimen.
Adenosine
;
Adenosine Triphosphate
;
Camptothecin
;
Cell Death
;
Cisplatin
;
Doxorubicin
;
Epirubicin
;
Etoposide
;
Fluorouracil
;
Gastrectomy
;
Humans
;
Lymph Nodes
;
Methotrexate
;
Organoplatinum Compounds
;
Paclitaxel
;
Polyphosphates
;
Stomach Neoplasms
;
Taxoids
4.In Vitro Adenosine Triphosphate Based Chemotherapy Response Assay in Gastric Cancer.
Seulkee PARK ; Yanghee WOO ; Hogeun KIM ; Yong Chan LEE ; Sungho CHOI ; Woo Jin HYUNG ; Sung Hoon NOH
Journal of Gastric Cancer 2010;10(4):155-161
PURPOSE: The purpose of this study was to investigate the reliability and the clinical applicability of the adenosine-triphosphate-based chemotherapy response assay (ATP-CRA) as a method of determining in vitro chemosensitivity in patients with gastric cancer. MATERIALS AND METHODS: A total of 243 gastric cancer tissue samples were obtained from gastrectomies performed between February 2007 and January 2010. We evaluated the effectiveness of the ATP-CRA assay in determining the chemosensitivity of gastric cancer specimens using eleven chemotherapeutic agents - etoposide, doxorubicin, epirubicin, mytomicin, 5-fluorouracil, oxaliplatin, irinotecan, docetaxel, paclitaxel, methotraxate, and cisplatin - for chemosensitivity studies using ATP-CRA. We assessed the failure rate, the cell death rate, and the chemosensitivity index. RESULTS: The failure rate of ATP-CRA was 1.6% (4/243). The mean coefficient of variation for triplicate ATP measurements was 6.5%. Etoposide showed the highest cell death rate (35.9%) while methotrexate showed the lowest (16.6%). The most active chemotherapeutic agent was etoposide, which most frequently ranked highest in the chemosensitivity test: 31.9% (51/160). Oxaliplatin was more active against early gastric cancers than advanced gastric cancers, whereas docetaxel was more active against advanced cancers. The lymph node negative group showed a significantly higher cell death rate than the lymph node positive group when treated with doxorubicin, epirubicin, and mitomycin. CONCLUSIONS: ATP-CRA is a stable and clinically applicable in vitro chemosensitivity test with a low failure rate. The clinical usefulness of ATP-CRA should be evaluated by prospective studies comparing the regimen guided by ATP-CRA with an empirical regimen.
Adenosine
;
Adenosine Triphosphate
;
Camptothecin
;
Cell Death
;
Cisplatin
;
Doxorubicin
;
Epirubicin
;
Etoposide
;
Fluorouracil
;
Gastrectomy
;
Humans
;
Lymph Nodes
;
Methotrexate
;
Organoplatinum Compounds
;
Paclitaxel
;
Polyphosphates
;
Stomach Neoplasms
;
Taxoids
5.Megalocytic Interstitial Nephritis Following Acute Pyelonephritis with Escherichia coli Bacteremia: A Case Report.
Hee Jin KWON ; Kwai Han YOO ; In Young KIM ; Seulkee LEE ; Hye Ryoun JANG ; Ghee Young KWON
Journal of Korean Medical Science 2015;30(1):110-114
Megalocytic interstitial nephritis is a rare form of kidney disease caused by chronic inflammation. We report a case of megalocytic interstitial nephritis occurring in a 45-yrold woman who presented with oliguric acute kidney injury and acute pyelonephritis accompanied by Escherichia coli bacteremia. Her renal function was not recovered despite adequate duration of susceptible antibiotic treatment, accompanied by negative conversion of bacteremia and bacteriuria. Kidney biopsy revealed an infiltration of numerous histiocytes without Michaelis-Gutmann bodies. The patient's renal function was markedly improved after short-term treatment with high-dose steroid.
Acute Disease
;
Acute Kidney Injury/complications/*drug therapy/pathology
;
Anti-Bacterial Agents/therapeutic use
;
Azithromycin/therapeutic use
;
Bacteremia/*drug therapy/microbiology/pathology
;
Cefotaxime/therapeutic use
;
Creatinine/blood
;
Escherichia coli
;
Escherichia coli Infections/*drug therapy/microbiology/pathology
;
Female
;
Humans
;
Kidney/pathology
;
Methylprednisolone/therapeutic use
;
Middle Aged
;
Nephritis, Interstitial/*drug therapy/immunology/pathology
;
Pyelonephritis/complications/*drug therapy/pathology
;
Renal Dialysis
;
Shock, Septic/drug therapy/microbiology
6.Pituitary Granulomatosis with Polyangiitis Presenting with Central Diabetes Insipidus.
In Young KIM ; Seulkee LEE ; Hee Jin KWON ; Keol LEE ; Kwai Han YOO ; Hoon Suk CHA ; Eun Mi KOH ; Jaejoon LEE
Journal of Rheumatic Diseases 2015;22(3):195-199
We report on a case of limited form of granulomatosis with polyangiitis (GPA) with pituitary involvement which presented with central diabetes insipidus. This rare form of GPA has not been reported in Korea. The patient presented with fever, headache, productive cough, nasal symptoms, and polyuria. Laboratory data and imaging studies demonstrated inflammatory lesions in nasal sinus and lungs. Pituitary stalk thickening and enhancement were observed on brain magnetic resonance imaging. The histopathology of the lung lesions showed chronic active granulomatous inflammation. Polyuria, hyperosmolar hypernatremia, and decreased urine osmolality which responded to synthetic vasopressin analog were consistent with central diabetes insipidus. Based on the clinical findings and histopathological results, a diagnosis of GPA with pituitary involvement was established. Treatment with desmopressin as well as concurrent glucocorticoids and immunosuppressant resulted in clinical improvement.
Brain
;
Cough
;
Deamino Arginine Vasopressin
;
Diabetes Insipidus, Neurogenic*
;
Diagnosis
;
Fever
;
Glucocorticoids
;
Headache
;
Humans
;
Hypernatremia
;
Inflammation
;
Korea
;
Lung
;
Magnetic Resonance Imaging
;
Osmolar Concentration
;
Pituitary Gland
;
Polyuria
;
Vasopressins
7.Rheumatoid Nodulosis with Recurrent Nodules: A Case Report.
Seulkee LEE ; Kwai Han YOO ; Keol LEE ; In Young KIM ; Hee Jin KWON ; Hoon Suk CHA ; Jiwon HWANG
Korean Journal of Medicine 2015;88(2):241-245
Rheumatoid nodulosis, a benign variant of rheumatoid arthritis (RA), is a rare condition characterized by multiple subcutaneous nodules and positive rheumatoid factor in the absence of systemic manifestations or joint disease. Asymptomatic nodules rarely require treatment, and are unlikely to recur after excision, except in cases in which RA develops. Here, we describe an unusual case of recurrent rheumatoid nodulosis in a 42-year-old female presenting with recurrent subcutaneous nodules on the plantar side of her left foot, which caused pain when walking. Nodules were initially excised to control symptoms; however, since the excision, the nodules have recurred twice in the absence of other RA symptoms.
Adult
;
Arthritis, Rheumatoid
;
Female
;
Foot
;
Humans
;
Joint Diseases
;
Rheumatoid Factor
;
Rheumatoid Nodule*
;
Synovitis
;
Walking
8.Three Cases of Overlap Syndrome Consisting of Systemic Sclerosis and Rheumatoid Arthritis.
Seulkee LEE ; Kwai Han YOO ; Keol LEE ; In Young KIM ; Hee Jin KWON ; Hyemin JEONG ; Eun Mi KOH
Korean Journal of Medicine 2015;88(3):350-355
Overlap syndrome is defined as a disease entity that fulfills the classification criteria of at least two different rheumatologic diseases simultaneously. Overlap of systemic sclerosis (SSc) and rheumatoid arthritis (RA) is less common than the overlap of polymyositis with SSc or systemic lupus erythematosus. Distinguishing RA from SSc can be difficult because arthralgia is a frequent symptom of both. We observed three cases of RA and SSc overlap. In each case, RA occurred in sequence with SSc, with a period of 4-15 years between the onset of each disease. In one case, the patient had diffuse SSc, which is rare among overlap syndrome patients. Previously, only one case of overlap syndrome involving SSc and RA has been reported in Korea; herein, we report our cases with a review of the literature.
Arthralgia
;
Arthritis, Rheumatoid*
;
Classification
;
Humans
;
Korea
;
Lupus Erythematosus, Systemic
;
Polymyositis
;
Scleroderma, Systemic*
9.Epidemiology of Polymyalgia Rheumatica in Korea.
In Young KIM ; Gi Hyeon SEO ; Seulkee LEE ; Hyemin JEONG ; Hyungjin KIM ; Jaejoon LEE ; Eun Mi KOH ; Hoon Suk CHA
Journal of Rheumatic Diseases 2014;21(6):297-302
OBJECTIVE: Polymyalgia rheumatica is a chronic inflammatory disease that affects people older than 50 years of age. The diagnosis is made based on clinical features, and the current standard of treatment is low-dose glucocorticoids. PMR is more commonly reported in Caucasians and females. However, epidemiological studies of PMR in Asian countries are scarce. We aimed to estimate the epidemiology of PMR in Korea. METHODS: This study was conducted by analyzing the Health Insurance Review and Assessment databases. We verified all claims between 2007 and 2012. Cases were included when PMR ICD-10 code (M 35.3) was recorded more than twice, and glucocorticoids were prescribed for > or =30 days. RESULTS: We identified 1,463 newly diagnosed cases of PMR during the 5 years. Among them, 992 (67.8%) were female, and the mean age at diagnosis was 66.9 years old. The annual incidence rate was 2.06 per 100,000 individuals aged over 50 years. The prevalence rate was 8.21 per 100,000 individuals in 2012. Incidence and prevalence appeared to increase with age. Prednisolone was the most commonly prescribed glucocorticoid. In half of the patients, the daily starting dose was 6~15 mg as prednisolone equivalents. CONCLUSION: This is the first study to investigate the epidemiology of PMR in Korea. The incidence and prevalence appeared to be considerably lower than those in Western populations. Both genetic and environmental factors might influence disease occurrence. In addition, the actual incidence may have been underestimated due to lack of awareness of PMR in clinical practice.
Asian Continental Ancestry Group
;
Diagnosis
;
Epidemiologic Studies
;
Epidemiology*
;
Female
;
Glucocorticoids
;
Humans
;
Incidence
;
Insurance, Health
;
International Classification of Diseases
;
Korea
;
Polymyalgia Rheumatica*
;
Prednisolone
;
Prevalence
10.Esophageal Mast Cell Infiltration in a 32-Year-Old Woman with Noncardiac Chest Pain.
Keol LEE ; Hee Jin KWON ; In Young KIM ; Kwai Han YOO ; Seulkee LEE ; Yang Won MIN ; Poong Lyul RHEE
Gut and Liver 2016;10(1):152-155
Noncardiac chest pain (NCCP) is one of the most common esophageal symptoms and lacks a clearly defined mechanism. The most common cause of NCCP is gastroesophageal reflux disease (GERD). One of the accepted mechanisms of NCCP in a patient without GERD has been altered visceral sensitivity. Mast cells may play a role in visceral hypersensitivity in irritable bowel syndrome. In this case, a patient with NCCP and dysphagia who was unresponsive to proton pump inhibitor treatment had an increased esophageal mast cell infiltration and responded to 14 days of antihistamine and antileukotriene treatment. We suggest that there may be a relationship between esophageal symptoms such as NCCP and esophageal mast cell infiltration.
Adult
;
Chest Pain/*etiology
;
Esophageal Diseases/*complications/drug therapy
;
Esophagus/cytology/pathology
;
Female
;
Histamine Antagonists/therapeutic use
;
Humans
;
Leukotriene Antagonists/therapeutic use
;
Mast Cells/metabolism
;
Mastocytosis/*complications/drug therapy