Umbilical Cord-Mesenchymal Stem Cell-Conditioned Medium Improves Insulin Resistance in C2C12 Cell

BackgroundUmbilical cord-mesenchymal stem cell-conditioned medium (UC-MSC-CM) has emerged as a promising cell-free therapy. The aim of this study was to explore the therapeutic effects of UC-MSC-CM on insulin resistance in C2C12 cell.MethodsInsulin resistance was induced by palmitate. Effects of UC-MSC-CM on insulin resistance were evaluated using glucose uptake, glucose transporter type 4 (GLUT4) translocation, the insulin-signaling pathway, and mitochondrial contents and functions in C2C12 cell.ResultsGlucose uptake was improved by UC-MSC-CM. UC-MSC-CM treatment increased only in membranous GLUT4 expression, not in cytosolic GLUT4 expression. It restored the insulin-signaling pathway in insulin receptor substrate 1 and protein kinase B. Mitochondrial contents evaluated by mitochondrial transcription factor A, mitochondrial DNA copy number, and peroxisome proliferator-activated receptor gamma coactivator 1-alpha were increased by UC-MSC-CM. In addition, UC-MSC-CM significantly decreased mitochondrial reactive oxygen species and increased fatty acid oxidation and mitochondrial membrane potential. There was no improvement in adenosine triphosphate (ATP) contents, but ATP synthesis was improved by UC-MSC-CM. Cytokine and active factor analysis of UC-MSC-CM showed that it contained many regulators inhibiting insulin resistance.ConclusionUC-MSC-CM improves insulin resistance with multiple mechanisms in C2C12 cell.

Umbilical Cord-Mesenchymal Stem Cell-Conditioned Medium Improves Insulin Resistance in C2C12 Cell

BackgroundUmbilical cord-mesenchymal stem cell-conditioned medium (UC-MSC-CM) has emerged as a promising cell-free therapy. The aim of this study was to explore the therapeutic effects of UC-MSC-CM on insulin resistance in C2C12 cell.MethodsInsulin resistance was induced by palmitate. Effects of UC-MSC-CM on insulin resistance were evaluated using glucose uptake, glucose transporter type 4 (GLUT4) translocation, the insulin-signaling pathway, and mitochondrial contents and functions in C2C12 cell.ResultsGlucose uptake was improved by UC-MSC-CM. UC-MSC-CM treatment increased only in membranous GLUT4 expression, not in cytosolic GLUT4 expression. It restored the insulin-signaling pathway in insulin receptor substrate 1 and protein kinase B. Mitochondrial contents evaluated by mitochondrial transcription factor A, mitochondrial DNA copy number, and peroxisome proliferator-activated receptor gamma coactivator 1-alpha were increased by UC-MSC-CM. In addition, UC-MSC-CM significantly decreased mitochondrial reactive oxygen species and increased fatty acid oxidation and mitochondrial membrane potential. There was no improvement in adenosine triphosphate (ATP) contents, but ATP synthesis was improved by UC-MSC-CM. Cytokine and active factor analysis of UC-MSC-CM showed that it contained many regulators inhibiting insulin resistance.ConclusionUC-MSC-CM improves insulin resistance with multiple mechanisms in C2C12 cell.

Umbilical Cord-Mesenchymal Stem Cell-Conditioned Medium Improves Insulin Resistance in C2C12 Cell

Background@#Umbilical cord-mesenchymal stem cell-conditioned medium (UC-MSC-CM) has emerged as a promising cell-free therapy. The aim of this study was to explore the therapeutic effects of UC-MSC-CM on insulin resistance in C2C12 cell. @*Methods@#Insulin resistance was induced by palmitate. Effects of UC-MSC-CM on insulin resistance were evaluated using glucose uptake, glucose transporter type 4 (GLUT4) translocation, the insulin-signaling pathway, and mitochondrial contents and functions in C2C12 cell. @*Results@#Glucose uptake was improved by UC-MSC-CM. UC-MSC-CM treatment increased only in membranous GLUT4 expression, not in cytosolic GLUT4 expression. It restored the insulin-signaling pathway in insulin receptor substrate 1 and protein kinase B. Mitochondrial contents evaluated by mitochondrial transcription factor A, mitochondrial DNA copy number, and peroxisome proliferator-activated receptor gamma coactivator 1-alpha were increased by UC-MSC-CM. In addition, UC-MSC-CM significantly decreased mitochondrial reactive oxygen species and increased fatty acid oxidation and mitochondrial membrane potential. There was no improvement in adenosine triphosphate (ATP) contents, but ATP synthesis was improved by UC-MSCCM. Cytokine and active factor analysis of UC-MSC-CM showed that it contained many regulators inhibiting insulin resistance. @*Conclusion@#UC-MSC-CM improves insulin resistance with multiple mechanisms in C2C12 cell.

Adult Stem Cell Treatment for Rheumatoid Arthritis

Since methotrexate began to be used in the treatment of rheumatoid arthritis (RA) 30 years ago, RA treatments have advanced rapidly from only reducing joint pain and inflammation to suppressing disease progression and joint destruction. In particular, the development of biologics and targeted anti-rheumatic drugs has almost made it possible to induce remission in patients with RA. On the other hand, the current RA treatments are still limited by adverse effects and treatment failure. Stem cell therapy has been suggested as an alternative treatment of RA, and preclinical studies and clinical trials using representative adult stem cells (ASCs), hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs), are currently underway. HSC therapy in RA has mostly progressed based on the concept of ‘immune reset’, in which the existing immune cells are replaced with healthy ones. HSC transplantation was completed relatively safely, and the patients showed a positive treatment response. Nevertheless, the treatment response of HSCs in RA depends on the conditioning regimen, and the efficacy did not persist for a long time. The MSCs possessed a hypo-immunogenicity, immune modulation effect and tissue regeneration capability, making them another promising candidate for the RA treatment. MSC transplantation in RA was found to be safe with few adverse effects, such as immune rejection or embolism, but it showed a partial and transient response. This review addresses the characteristics of ASCs, focusing specifically on HSCs and MSCs, and summarizes the results of preclinical studies and clinical trials of ASC therapy in RA.

Clinical Manifestations of Korean Adult Patients with Henoch-Schonlein Purpura / 대한류마티스학회지

OBJECTIVE: We investigated the clinical data and analyzed the significant prognostic factors for outcomes in Korean adult patients with Henoch-Schonlein Purpura (HSP). METHODS: We retrospectively reviewed the medical records of 52 patients over 20 years-old, who visited the Yonsei University Severance Hospital from December 1999 to November 2009, and fulfilled the classification criteria for HSP. We investigated the epidemiologic data, clinical features, renal biopsy findings, laboratory results and disease outcomes. RESULTS: The median age was 43.5 (20~83) years old and 29 out of 52 patients (55.8%) were male. HSP exhibited seasonal variation and most frequently developed in winter (42.3%), followed by spring (25.0%). Upper respiratory infection was the most common known preceding event for HSP development. Skin manifestations were observed in all subjects, followed by kidney (80.8%), gastro-intestine (57.7%) and joints (26.9%). After a median follow-up period 14.5 (1~227) months, 12 patients experienced HSP relapse (23.1%), and 7 patients had chronic renal failure (13.4%). Univariate analysis showed that renal insufficiency (p=0.002) and nephritic syndrome (p=0.026) at diagnosis were significantly related to the development of chronic renal failure. Of the two parameters, only initial renal insufficiency was found to be a significant predictive value for chronic renal failure (OR=28.7, p=0.001, 95% confidential interval 3.6~225.3). CONCLUSION: Renal insufficiency at diagnosis may be a useful predictive factor for progression to chronic renal failure in Korean adult patients with HSP.

A Case of Escherichia Coli Sternoclavicular Septic Arthritis / 대한류마티스학회지

Septic arthritis of the sternoclavicular joint is a rare condition. The predisposing risk factors include intravenous drug abuse, subclavian vein catheter placement, diabetes mellitus and trauma. Delayed or inadequate management can lead to irreversible joint damage with subsequent disability, even death. We report a 48-year-old female patient who presented with right sternoclavicular joint swelling and right shoulder pain. Magnetic resonance imaging of the sternum showed swelling of the right sternoclavicular joint with gadolinium enhancement. Synovial fluid and bone tissue culture revealed Escherichia coli (E.coli), and confirmed the diagnosis of sternoclavicular septic arthritis. She was successfully treated with surgical debridement and ciprofloxacin without recurrence. This is the first case report of E.coli sternoclavicular septic arthritis in Korea.

A Case of Wegener's Granulomatosis Presenting with Cerebral Infarction and Intracerebral Hemorrhage / 대한류마티스학회지

Wegener's granulomatosis is a multisystem necrotizing vasculitis that primarily involves the upper and lower respiratory tract and kidneys but can affect almost any organ, including the central nervous system. Cerebral infarction and intracerebral hemorrhage are rare neurologic complications of Wegener's granulomatosis. We report on a 52-year-old male patient with Wegener's granulomatosis presenting with a cerebral infarction and subsequent intracerebral hemorrhage. He was successfully treated with high dose corticosteroid and cyclophosphamide.

A Case of Dermatomyositis Showing Vesicular Lesion Associated with Ovarian Cancer / 대한류마티스학회지

Dermatomyositis is a rare inflammatory myopathy with characteristic skin manifestations and accompanied by muscular weakness. Vesicle formation in dermatomyositis is rare. We report a case of dermatomyositis associated with ovarian cancer in a 62-year-old woman who had vesicles and bullae on her arms. She had erythema and edema on the face, chest, abdomen, and shoulder for 2 months. Diagnosis of dermatomyositis was established by clinical manifestations, muscle enzyme elevation, and a characteristic electromyogram. She was successfully treated with cyclosporin and high doses of steroids.

A case of adult-onset Still's disease combined with Sjogren's syndrome / 대한내과학회지

Sjogren's syndrome is a chronic, slowly progressive autoimmune disease in which the exocrine glands are damaged by lymphocytic infiltration, resulting in xerostomia and xerophthalmia. Adult-onset Still's disease (AOSD) is a multi-systemic inflammatory disorder, characterized by a high spiking fever, an evanescent salmon-colored rash, arthralgia or arthritis, lymphadenopathy, leukocytosis, and the involvement of various organs. We report the case of a 59-year-old female patient with Sjogren's syndrome who presented with a fever of unknown origin. She was diagnosed with AOSD based on her high spiking fever, evanescent skin rash, arthralgia, lymphadenopathy, leukocytosis, sore throat, and hyperferritinemia after extensive investigations were performed to exclude other diseases. Her AOSD symptoms were successfully treated with high-dose glucocorticoid and methotrexate, without recurrence. We describe the case of a 59-year-old female patient with Sjogren's syndrome and AOSD.

A case of adult-onset Still's disease combined with Sjogren's syndrome / 대한내과학회지

Sjogren's syndrome is a chronic, slowly progressive autoimmune disease in which the exocrine glands are damaged by lymphocytic infiltration, resulting in xerostomia and xerophthalmia. Adult-onset Still's disease (AOSD) is a multi-systemic inflammatory disorder, characterized by a high spiking fever, an evanescent salmon-colored rash, arthralgia or arthritis, lymphadenopathy, leukocytosis, and the involvement of various organs. We report the case of a 59-year-old female patient with Sjogren's syndrome who presented with a fever of unknown origin. She was diagnosed with AOSD based on her high spiking fever, evanescent skin rash, arthralgia, lymphadenopathy, leukocytosis, sore throat, and hyperferritinemia after extensive investigations were performed to exclude other diseases. Her AOSD symptoms were successfully treated with high-dose glucocorticoid and methotrexate, without recurrence. We describe the case of a 59-year-old female patient with Sjogren's syndrome and AOSD.

Kikuchi-Fujimoto's Disease with Adult Onset Still's Disease / 대한류마티스학회지

Kikuchi-Fujimoto's disease (KFD), or histiocytic necrotizing lymphadenitis, is a rare benign and self-limiting disease. KFD are confused with systemic autoimmune disease as they present with localized lymphadenopathy, fever, fatigue, arthritis, leukopenia. Furthermore as KFD can occur associated with other autoimmune disease, we need to diagnose carefully. Here, we describe a case of 27-year-old female patient, diagnosed as KFD, who subsequently developed adult onset Still's disesase (AOSD). As far as we know, this is the first case of KFD with AOSD in Korea.

Serum Amyloid A as a Useful Indicator of Disease Activity in Patients with Ankylosing Spondylitis

PURPOSE: To investigate whether serum amyloid A (SAA) levels are increased in patients with ankylosing spondylitis (AS) and whether its levels correlate well with AS disease activity. MATERIALS AND METHODS: Thirty-eight patients with AS and 38 age- and sex-matched control subjects were enrolled in this cross-sectional study. Their SAA levels were quantitatively measured by immunonephelometry. An established, self-administered instrument for evaluating disease activity (Bath Ankylosing Spondylitis Disease Activity Index, BASDAI) was used to measure and acute phase reactants, including erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), in patients with AS. RESULTS: Patients with AS had a significantly higher mean SAA level than controls (9.52 +/- 7.49mg/L versus 2.73 +/- 1.57mg/L, p < 0.05), and the mean BASDAI score of patients with elevated SAA levels was significantly higher than that of patients with normal SAA levels (5.6 +/- 1.3 versus 4.4 +/- 1.5, p < 0.05). SAA levels showed significant correlations with BASDAI scores (r=0.431, p=0.007), ESR (r=0.521, p=0.001) and CRP levels (r=0.648, p < 0.001). Additionally, the correlation between ESR and CRP levels also appeared significant (r=0.703, p < 0.001). In those with normal ESR or CRP levels, SAA levels and BASDAI scores were elevated (p < 0.05) and showed a trend of positive correlation with one another. CONCLUSION: Our data showed that SAA levels were increased in patients with AS and correlated well with disease activity. These findings suggest that SAA can be used as a valuable indicator of disease activity in AS.

Malignancies in Korean Patients with Inflammatory Myopathy

The aim of this study was to assess the prevalence and the common type of malignancies in Korean patients with polymyositis (PM) and dermatomyositis (DM) and to evaluate the differences of clinical and laboratory findings between patients with malignancy and those without malignancy. Forty-one Korean patients, who were diagnosed as PM or DM, were enrolled in this study. They fulfilled the Bohan and Peter's criteria for a definite diagnosis of PM and DM. Patients with PM were 25 and those with DM were 16. Eleven out of 41 patients (26.8%) had malignancies. The malignancy was diagnosed simultaneously or later in 81.8% of patients with inflammatory myopathy (IM). The breast cancer was the most common malignancy. In this study, forty three years old as a screening age for malignancy had 88.9% sensitivity and 50.2% specificity. The serum levels of creatine kinase (CK) were significantly lower in patients with malignancy than those without malignancy.

A Case of HIV Infection by Intravenous Drug Abuse

Intravenous (IV) drug abuse is one of important transmission modes of human immunodeficiency virus (HIV) infection. IV drug abuse in HIV epidemics is frequent in western countries. In Korea, however, no case has been definitely identified although possibility of such infection route does exist considering rising number of IV drug use (IDU). Recently, we have experienced a case of HIV infection by IDU. We herein offer the case with review of literature.

A Case of Pneumocystis carinii Pneumonia in a Patient with Behcet Syndrome

Pneumocystis carinii pneumonia (PCP) is one of the most common causes of infection in patients with HIV infection. With the development of effective prophylactic agent, the incidence of PCP in patients with HIV infection has been declining. On the other hand, however, the incidence of PCP has been increasing in immunocompromised hosts without HIV infection, such as rheumatoid arthritis, bone marrow transplantaion and Behcet syndrome. The increased occurrence of PCP in non-HIV- infected subjects has been attributed to several factors, such as use of stronger immunosuppressive regimens, higher awareness of PCP, advanced diagnostic technology and nosocomial spread of P. carinii. The occurrence of PCP in patients who receive immunosuppressive drugs for autoimmune disease has not been well known in Korea. We report a patient with Behcet syndrome who suffered from PCP after immunosuppressive drugs.

A Case of HIV Infection by Intravenous Drug Abuse

Intravenous (IV) drug abuse is one of important transmission modes of human immunodeficiency virus (HIV) infection. IV drug abuse in HIV epidemics is frequent in western countries. In Korea, however, no case has been definitely identified although possibility of such infection route does exist considering rising number of IV drug use (IDU). Recently, we have experienced a case of HIV infection by IDU. We herein offer the case with review of literature.

A Case of Pneumocystis carinii Pneumonia in a Patient with Behcet Syndrome

Pneumocystis carinii pneumonia (PCP) is one of the most common causes of infection in patients with HIV infection. With the development of effective prophylactic agent, the incidence of PCP in patients with HIV infection has been declining. On the other hand, however, the incidence of PCP has been increasing in immunocompromised hosts without HIV infection, such as rheumatoid arthritis, bone marrow transplantaion and Behcet syndrome. The increased occurrence of PCP in non-HIV- infected subjects has been attributed to several factors, such as use of stronger immunosuppressive regimens, higher awareness of PCP, advanced diagnostic technology and nosocomial spread of P. carinii. The occurrence of PCP in patients who receive immunosuppressive drugs for autoimmune disease has not been well known in Korea. We report a patient with Behcet syndrome who suffered from PCP after immunosuppressive drugs.

Neuropsychiatric Lupus Diagnosed by Brain PET: A Case Report / 대한류마티스학회지

Neuropsychiatric lupus is a complication of systemic lupus erythematosus (SLE) characterized by profound metabolic alteration including impaired blood flow, ischemia, decreased aerobic metabolism and progressive neuronal loss of central nervous system. Because of the lack of useful diagnostic methods, it's diagnosis and management is difficult. Recently, F-18- fluoro-2-deoxy-D-glucose positron emission tomography (18FDG-PET) is considered to be a sensitive and reliable method for evaluating SLE patients with neuropsychiatric involvement as compared with brain computed tomography (CT) or magnetic resornance imaging (MRI). In SLE patient having mild or severe neuropsychiatric manifestations, 18FDG-PET shows hypo- or hypermetabolism by different glucose utilization in brain tissue. We experienced a 23-year-old woman with SLE who presented with seizure and loss of consciousness. Initially, brain MRI finding was negative, but brain 18FDG-PET revealed significant hypometabolism in the cerebral hemisphere at active stage of disease and complete resolution of metabolic abnormalities after treatment. Herein, we report a case of neuropsychiatric lupus diagnosed by brain 18FDG-PET.

A Case of Lung Metastasis of Mesoblastic Nephroma in Adulthood / 결핵

Mesoblastic nephroma is a neoplasm of the kidney which is characterized by interlacing bundles of spindle mesenchymal cells. It is usually diagnosed during the first six months of life and is mostly benign. Incidence in adults is exceedingly rare. In most cases, only total excision is required without postoperative adjuvant therapy, and the rare cases of local recurrence have usually been related to incomplete removal. However, mesoblastic nephroma may behave aggressively, in contrast to a congenital mesoblastic nephroma. Several cases of metastatic mesoblastic nephroma have been previously described. We report herein a case of a 42-year-old woman with mesoblastic nephroma which recurred as a large metastatic lung mass seven years after the nephrectomy. The patient presented with chest wall discomfort for four days. Seven years previously, total nephrectomy had been performed because of a right renal tumor which had been diagnosed as a mesoblastic nephroma. There had been no evidence of recurrence for five years, after which she discontinued follow-up. On readmission two years later, chest X-ray and CT scan revealed a large lung mass in the left upper lobe. It was completely excised and the pathologic examination was identical with that of the original renal tumor. Synovial sarcoma was excluded because the fusion transcripts of the SYT-SSX fusion gene associated with the t(X;18) translocation were negative. The final diagnosis was a lung metastasis of mesoblastic nephroma and the patient remained free of disease for 7 months postoperatively.