It remains unclear whether immunosuppressive agents are effective in patients with immunoglobulin A nephropathy (IgAN). We investigated the efficacy of a mycophenolate mofetil (MMF) and corticosteroid combination therapy in patients with advanced IgAN. Methods: We conducted a multicenter, randomized, placebo-controlled, parallel-group study of 48 weeks administration of MMF and corticosteroids in biopsy-proven advanced IgAN patients with estimated glomerular filtration rate (eGFR) of 20–50 mL/min/1.73 m2 and urine protein-to-creatinine ratio (UPCR) of >0.75 g/day. The primary outcome was complete (UPCR < 0.3 g/day) or partial (>50% reduction of UPCR compared to baseline) remission at 48 weeks. Results: Among the 48 randomized patients, the percentage that achieved complete or partial remission was greater in the combination therapy group than in the control group (4.2% vs. 0% and 29.1% vs. 5.0%, respectively). Compared with the combination therapy group, eGFR in the control group decreased significantly from week 36 onward, resulting in a final adjusted mean change of –4.39 ± 1.22 mL/min/1.73 m2 (p = 0.002). The adjusted mean changes after 48 weeks were 0.62 ± 1.30 and –5.11 ± 1.30 mL/min/1.73 m2 (p = 0.005) in the treatment and control groups, respectively. The UPCR was significantly different between the two groups; the adjusted mean difference was –0.47 ± 0.17 mg/mgCr and 0.07 ± 0.17 mg/mgCr in the treatment and control group, respectively (p = 0.04). Overall adverse events did not differ between the groups. Conclusion: In advanced IgAN patients with a high risk for disease progression, combined MMF and corticosteroid therapy appears to be beneficial in reducing proteinuria and preserving renal function.

BACKGROUND/AIMS: Ambulatory blood pressure (BP) monitoring has been widely recommended for evaluating the status of BP, but is lacking in practicality. Determination of the specific time points for BP measurement that are representative of 24-hour mean BP could be useful and convenient in hypertensive patients with chronic kidney disease (CKD). METHODS: A total of 1,317 patients for whom 24-hour ambulatory BP monitoring was performed were enrolled in a multicenter study on hypertensive CKD. We analyzed the time points at which systolic blood pressure (SBP) values exhibited the smallest differences from 24-hour mean SBP (mSBP). We included office mSBP and analyzed the relationships between SBPs at the office and the time points with the smallest differences from 24-hour mSBP using several methods. RESULTS: The time points with the smallest differences from 24-hour mSBP were 7:00 AM, 2:00 PM, and 9:30 PM. In regression analysis, SBPs at 7:00 AM and 9:30 PM were better correlated with 24-hour mSBP than SBPs at 2:00 PM and the office. The proportions of patients with SBPs within 30% of 24-hour mSBP were higher at 7:00 AM and 9:30 PM. The best consistency between the uncontrolled hypertensive groups, defined as > or = 135 mmHg of 24-hour mSBP and higher values of SBPs corresponding to 135 mmHg of 24-hour mSBP, were observed at the 7:00 AM and 9:30 PM time points. CONCLUSIONS: The specific time points for SBPs that correlated well with 24-hour mSBP in hypertensive CKD patients were 7:00 AM and 9:30 PM.
Adult ; Aged ; *Blood Pressure ; Blood Pressure Monitoring, Ambulatory/*methods ; Circadian Rhythm ; Cross-Sectional Studies ; Female ; Humans ; Hypertension/*diagnosis/physiopathology ; Male ; Middle Aged ; Office Visits ; Predictive Value of Tests ; Prospective Studies ; Renal Insufficiency, Chronic/*diagnosis/physiopathology ; Republic of Korea ; Time Factors ; Young Adult

It is known that blood pressure variability (BPV) can independently affect target organ damage (TOD), even with normal blood pressure. There have been few studieson chronic kidney disease (CKD) patients. We evaluated the relationship between BPV and TOD in a cross-sectional, multicenter study on hypertensive CKD patients. We evaluated 1,173 patients using 24-hr ambulatory blood pressure monitoring. BPV was defined as the average real variability, with a mean value of the absolute differences between consecutive readings of systolic blood pressure. TOD was defined as left ventricular hypertrophy (LVH) (by the Romhilt-Estes score > or =4 in electrocardiography) and kidney injury (as determined from an estimated glomerular filtration rate [eGFR]<30 mL/min/1.73 m2 and proteinuria).The mean BPV of the subjects was 15.9+/-4.63 mmHg. BPV displayed a positive relationship with LVH in a univariate analysis and after adjustment for multi-variables (odds ratio per 1 mmHg increase in BPV: 1.053, P=0.006). In contrast, BPV had no relationship with kidney injury. These data suggest that BPV may be positively associated with LVH in hypertensive CKD patients.
Adult ; Aged ; Blood Pressure/*physiology ; Blood Pressure Monitoring, Ambulatory ; Cross-Sectional Studies ; Electrocardiography ; Female ; Glomerular Filtration Rate ; Humans ; Hypertension/*complications/*diagnosis ; Hypertrophy, Left Ventricular/*physiopathology ; Kidney/injuries ; Male ; Middle Aged ; Odds Ratio ; Proteinuria/complications ; Renal Insufficiency, Chronic/*complications/*diagnosis

We investigated the inhibitory effects of hesperidin on melanogenesis. To find melanosome transport inhibitor from natural products, we collected the structural information of natural products from Korea Food and Drug Administration (KFDA) and performed pharmacophore-based in silico screening for Rab27A and melanophilin (MLPH). Hesperidin did not inhibit melanin production in B16F10 murine melanoma cells stimulated with alpha-melanocyte stimulating hormone (alpha-MSH), and also did not affect the catalytic activity of tyrosinase. But, hesperidin inhibited melanosome transport in melanocyte and showed skin lightening effect in pigmented reconstructed epidermis model. Therefore, we suggest that hesperidin is a useful inhibitor of melanosome transport and it might be applied to whitening agent.
Biological Agents ; Computer Simulation ; Epidermis ; Hesperidin* ; Korea ; Mass Screening ; Melanins ; Melanocytes ; Melanoma ; Melanosomes* ; Monophenol Monooxygenase ; Skin ; United States Food and Drug Administration

Changes in the expression profiles of specific proteins leads to serious human diseases, including colitis. The proteomic changes related to colitis and the differential expression between tuberculous (TC) and ulcerative colitis (UC) in colon tissue from colitis patients has not been defined. We therefore performed a proteomic analysis of human TC and UC mucosal tissue. Total protein was obtained from the colon mucosal tissue of normal, TC, and UC patients, and resolved by 2-dimensional electrophoresis (2-DE). The results were analyzed with PDQuest using silver staining. We used matrix-assisted laser desorption ionization time-of-flight/time-of-flight spectrometry (MALDI TOF/TOF) to identify proteins differentially expressed in TC and UC. Of the over 1,000 proteins isolated, three in TC tissue and two in UC tissue displayed altered expression when compared to normal tissue. Moreover, two proteins were differentially expressed in a comparative analysis between TC and UC. These were identified as mutant beta-actin, alpha-enolase and Charcot-Leyden crystal protein. In particular, the expression of alpha-enolase was significantly greater in TC compared with normal tissue, but decreased in comparison to UC, implying that alpha-enolase may represent a biomarker for differential diagnosis of TC and UC. This study therefore provides a valuable resource for the molecular and diagnostic analysis of human colitis.
Actins ; Colitis ; Colitis, Ulcerative ; Colon ; Diagnosis, Differential ; Electrophoresis ; Glycoproteins ; Humans ; Lysophospholipase ; Mucous Membrane ; Phosphopyruvate Hydratase ; Proteins ; Proteomics ; Silver Staining ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; Spectrum Analysis ; Ulcer

BACKGROUND: Fibrous hamartoma is the key pathology of congenital pseudarthrosis of the tibia (CPT), which was shown to have low osteogenicity and high osteoclastogenicity. This study further investigated the mechanism of impaired osteoblastic differentiation of fibrous hamartoma cells. METHODS: Fibroblast-like cells were obtained from enzymatically dissociated fibrous hamartomas of 11 patients with CPT associated with neurofibromatosis type I (NF1). Periosteal cells were also obtained from the distal tibial periosteum of 3 patients without CPT or NF1 as control. The mRNA levels of Wnt ligands and their canonical receptors, such as Lrp5 and beta-catenin, were assayed using reverse transcriptase PCR (RT-PCR). Changes in mRNA expression of osteoblast marker genes by rhBMP2 treatment were assayed using quantitative real time RT-PCR. Changes in mRNA expression of transcription factors specifically involved in osteoblastic differentiation by rhBMP2 treatment was also assayed using quantitative real-time RT-PCR. RESULTS: Wnt1 and Wnt3a mRNA expression was lower in fibrous hamartoma than in tibial periosteal cells, but their canonical receptors did not show significant difference. Response of osteoblastic marker gene expression to rhBMP2 treatment showed patient-to-patient variability. Col1a1 mRNA expression was up-regulated in most fibrous hamartoma tissues, osteocalcin was up-regulated in a small number of patients, and ALP expression was down-regulated in most fibrous hamartoma tissues. Changes in mRNA expression of the transcription factors in response to rhBMP2 also showed factor-to-factor and patient-to-patient variability. Dlx5 was consistently up-regulated by rhBMP2 treatment in all fibrous hamartoma tissues tested. Msx2 expression was down-regulated by rhBMP2 in most cases but by lesser extent than control tissue. Runx2 expression was up-regulated in 8 out of 18 fibrous hamartoma tissues tested. Osterix expression was up-regulated in 2 and down-regulated in 3 fibrous hamartoma tissues. CONCLUSIONS: Congenital pseudarthrosis of the tibia appears to be caused by fibrous hamartoma originating from aberrant growth of Nf1 haploinsufficient periosteal cells, which failed in terminal osteoblastic differentiation and arrested at a certain stage of this process. This pathomechanism of CPT should be targeted in the development of novel therapeutic biologic intervention.
Adolescent ; *Cell Differentiation ; Cells, Cultured ; Child ; Child, Preschool ; Female ; Hamartoma/complications/*pathology ; Humans ; Infant ; Low Density Lipoprotein Receptor-Related Protein-5/metabolism ; Male ; Neurofibromatosis 1/complications/*pathology ; Osteoblasts/*pathology ; Periosteum/pathology ; Pseudarthrosis/complications/*congenital/pathology/physiopathology ; Receptors, Wnt/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Tibia/*pathology ; Transcription Factors/metabolism ; Wnt1 Protein/metabolism ; Wnt3A Protein/metabolism ; beta Catenin/metabolism

BACKGROUND/AIMS: Intestinal involvement with bleeding and perforation is one of the main causes of morbidity and mortality in patients with Behcet's disease (BD); however, the clinical course of intestinal BD has not been defined. The aim of this study was to determine the clinical course of intestinal BD based on the characteristics of ulcers visualized during colonoscopy. METHODS: We retrospectively reviewed the medical records and colonoscopic findings of 41 patients with intestinal BD. All patients were classified into subgroups according to ulcer depth, size, and number, and we analyzed the clinical manifestations, subset type of BD, medications, surgical procedures, and relapse rate among the subgroups. RESULTS: The median age at the time of diagnosis was 38 years (range, 18-74 years); 25 patients were females (M:F=1:1.56). Abdominal pain (n=40), diarrhea (n=27), and RLQ tenderness (n=21) were common symptoms. The number of complete, incomplete, and suspected types was 3, 17, and 21, respectively. In an analysis according to ulcer depth, the rate of steroid use and intestinal surgeries was more frequent in the deep ulcer group compared with the aphthous and shallow ulcer groups (50.0% vs. 0% vs. 17.6%; P=0.012; 42.9% vs. 0% vs. 23.5%: P=0.013) The rate of steroid use and relapse tended to be higher as the size of the ulcer increased; however, there was no difference in the rates of steroid use, surgeries, and relapse based on the number of intestinal ulcers. CONCLUSIONS: The prognosis was worse in patients with intestinal BD who have deeper and larger ulcers. Therefore, we suggest that such patients need to be treated aggressively.
Abdominal Pain ; Colonoscopy ; Diarrhea ; Female ; Hemorrhage ; Humans ; Medical Records ; Prognosis ; Recurrence ; Retrospective Studies ; Ulcer

BACKGROUND/AIMS: Intestinal involvement with bleeding and perforation is one of the main causes of morbidity and mortality in patients with Behcet's disease (BD); however, the clinical course of intestinal BD has not been defined. The aim of this study was to determine the clinical course of intestinal BD based on the characteristics of ulcers visualized during colonoscopy. METHODS: We retrospectively reviewed the medical records and colonoscopic findings of 41 patients with intestinal BD. All patients were classified into subgroups according to ulcer depth, size, and number, and we analyzed the clinical manifestations, subset type of BD, medications, surgical procedures, and relapse rate among the subgroups. RESULTS: The median age at the time of diagnosis was 38 years (range, 18-74 years); 25 patients were females (M:F=1:1.56). Abdominal pain (n=40), diarrhea (n=27), and RLQ tenderness (n=21) were common symptoms. The number of complete, incomplete, and suspected types was 3, 17, and 21, respectively. In an analysis according to ulcer depth, the rate of steroid use and intestinal surgeries was more frequent in the deep ulcer group compared with the aphthous and shallow ulcer groups (50.0% vs. 0% vs. 17.6%; P=0.012; 42.9% vs. 0% vs. 23.5%: P=0.013) The rate of steroid use and relapse tended to be higher as the size of the ulcer increased; however, there was no difference in the rates of steroid use, surgeries, and relapse based on the number of intestinal ulcers. CONCLUSIONS: The prognosis was worse in patients with intestinal BD who have deeper and larger ulcers. Therefore, we suggest that such patients need to be treated aggressively.
Abdominal Pain ; Colonoscopy ; Diarrhea ; Female ; Hemorrhage ; Humans ; Medical Records ; Prognosis ; Recurrence ; Retrospective Studies ; Ulcer

Lymphoepithelioma-like carcinoma (LELC) is a rare cancer and it makes up about 1~4% of all gastric malignancies. The main histologic feature of LELC is a lymphoid stroma. LELC is rare in that its shape is similar to that of submucosal tumor (SMT). Although SMT can be divided into malignant and benign tumors, using endoscopic ultrasonography (EUS) and EUS-guided fine needle aspiration, there are still many cases that can't be discriminated, and it is especially difficult to obtain specimens due to the small size of SMT. There have been some recent trials to endoscopic remove small SMTs for the purpose of making an exact diagnosis and guiding therapy. We report here a case of gastric LELC that exhibited the features of a submucosal tumor, and this LELC was removed by endoscopic enucleation. We also briefly review the relevant medical literature.
Biopsy, Fine-Needle ; Endoscopy ; Endosonography

BACKGROUND: Triple immunosuppressant therapy including anti-metabolites is the representative immunosuppressive therapy after renal transplantation. This study is to evaluate the factors that influence Mycophenolate sodium (MPS, Myfortic, Novartis, Basel, Switzerland) dosage patterns in renal transplantation patients who take MPS as an inosine monophosphate dehydrogenase (IMPDH) among antimetabolites. METHODS: From May 2007 to April 2008, 16 clinical departments of 14 transplantation centers in Korea retrospectively performed a survey on 650 renal transplantation recipients taking MPS. This survey collected personal information, clinical factors related to transplantation and immunosuppressive therapy. RESULTS: The mean age of the patients was 43.0+/-12.0 (7~75) and the study included 364 males (56.0%) and 286 females (44.0%). The average follow up period after renal transplantation was 49.5+/-53.4 (1~307) months. There were 366 (56.3%) living related cases, 145 (22.3%) living non-related cases and 139 (21.4%) deceased donor cases. Cyclosporine was the most common calcineurin inhibitor (CNI) used in combination therapy with MPS (476 cases, 73.2%) followed by tacrolimus (169 cases, 26.0%). The mean daily dose of MPS was 909.7+/-336.3 (180~1,620)mg and the mean daily dose per kg was 15.3+/-5.9 (2.65~32.73)mg/kg. The daily dose showed significant positive correlation with patient body weight but the daily dose per kg showed negative correlation. The daily dose of MPS was significantly higher in the combination therapy with cyclosporine than that with tacrolimus. The daily dose and the dose per kg decreased with increment of recipient age and post-transplant period. CONCLUSIONS: Our study concluded that MPS dosages correlated with the combined type of CNI, post-transplant period and age.
Body Weight ; Calcineurin ; Cyclosporine ; Female ; Follow-Up Studies ; Humans ; Inosine Monophosphate ; Kidney Transplantation ; Korea ; Male ; Mycophenolic Acid ; Oxidoreductases ; Retrospective Studies ; Sodium ; Tacrolimus ; Tissue Donors ; Transplants