Rafts, cholesterol- and sphingolipid-rich membrane microdomains, have been shown to play an important role in immune cell activation. More recently rafts were implicated in the signal transduction by members of the TNF receptor (TNFR) family. In this study, we provide evidences that the raft microdomain has a crucial role in RANK (receptor activator of NF-kappaB) signaling. We found that the majority of the ectopically expressed RANK and substantial portion of endogenous TRAF2 and TRAF6 were detected in the low-density raft fractions. In addition, TRAF6 association with rafts was increased by RANKL stimulation. The disruption of rafts blocked the TRAF6 translocation by RANK ligand and impeded the interaction between RANK and TRAF6. Our observations demonstrate that proper RANK signaling requires the function of raft membrane microdomains.
Carrier Proteins/metabolism ; Glycoproteins/*metabolism ; Human ; Membrane Glycoproteins/metabolism ; Membrane Microdomains/*metabolism ; Protein Transport/physiology ; Proteins/*metabolism ; Receptors, Cytoplasmic and Nuclear/*metabolism

OBJECTIVES: Osteoporosis is a disease of bones that is thought to result from an imbalance between bone resorption and bone formation. Although osteoporosis itself has no symptoms, osteoporosis caused by osteoclasts leads to an increased risk of fracture. Here we examined the effects of cornus officinalis on receptor activator of nuclear factor-kappaB ligand (RANKL)-mediated osteoclast differentiation. METHODS: We evaluated the effects of cornus officinalis on RANKL-induced osteoclast differentiation from bone marrow-derived macrophages (BMMs) and performed a cytotoxicity assay, reverse transcriptase-polymerase chain reaction (RT-PCR), and Western blot analysis. RESULTS: Cornus officinalis significantly inhibits RANKL-mediated osteoclast differentiation in a dose-dependent manner, but without cytotoxicity against BMMs. The mRNA expression of tartrate-resistant acid phosphatase (TRAP), osteoclast-associated receptor (OSCAR), c-Fos, and nuclear factor of activated T cells cytoplasmic 1 (NFATc1) in BMMs treated with RANKL was considerably inhibited by cornus officinalis treatment. Also, cornus officinalis inhibits the protein expression of c-Fos and NFATc1. Cornus officinalis greatly inhibits RANKL-induced phosphorylation of p38 and c-JUN N-terminal kinase (JNK). Also, cornus officinalis significantly suppresses RANKL-induced degradation of I-kappaB. CONCLUSIONS: Taken together, our results suggest that cornus officinalis may be a useful the treatment of osteoporosis.
Acid Phosphatase ; Blotting, Western ; Bone Resorption ; Cornus ; Cytoplasm ; Isoenzymes ; JNK Mitogen-Activated Protein Kinases ; Macrophages ; Osteoclasts ; Osteogenesis ; Osteoporosis ; Phosphorylation ; RANK Ligand ; Receptor Activator of Nuclear Factor-kappa B ; RNA, Messenger ; T-Lymphocytes

The purpose of this study was to investigate the fluoroquinolone resistance frequency of Enterococcus spp. from normal chicken feces and to analyse mutations of the gyrA and parC gene associated with fluoroquinolone resistance. Among 52 Enterococcus faecalis and 25 E. faecium isolates, 23 (44.2%) E. faecalis and 7 (28.0%) E. faecium were resistant to ciprofloxacin (CIP) by disc diffusion method. Genetic exchange in gyrA and parC gene among 2 CIP intermediate isolates and 15 CIP resistant isolates were found in the amino acid codon of Ser-83 and Asp-87, and Ser-80 and Glu-84, respectively. These mutants contained a change from Ser to Phe, Val, Tyr, Ile, Thr or Pro at codon 83 and from Glu to Gly or Leu at codon 87 in gyrA gene, and a change from Ser to Ile or Thr at codon 80 and from Glu to Asp or Lys at codon 84 in parC gene. The isolates with mutation in gyrA regardless of a mutation in parC showed high resistance (MIC > or =32 microgram/ml) to CIP, enrofloxacin, norfloxacin and ofloxacin. These results suggested that gyrA gene is the primary target for 4 fluoroquinolones resistance in Enterococcus spp.
Chickens* ; Ciprofloxacin ; Codon ; Diffusion ; Enterococcus faecalis ; Enterococcus* ; Feces* ; Fluoroquinolones ; Norfloxacin ; Ofloxacin ; Viperidae

Among the several rotenoids, amorphigenin is isolated from the leaves of Amopha Fruticosa and it is known that has anti-proliferative effects and anti-cnacer effects in many cell types. The main aim of this study was to investigate the effects of amorphigenin on osteoclast differentiation in vitro and on LPS treated inflammatory bone loss model in vivo. We show here that amorphigenin inhibited RANKL-induced osteoclast differentiation from bone marrow macrophages in a dose dependent manner without cellular toxicity. Anti-osteoclastogenic properties of amorphigenin were based on a down-regulation of c-fos and NFATc1. Amorphigenin markedly inhibited RANKL-induced p38 and NF-kappaB pathways, but other pathways were not affected. Micro-CT analysis of the femurs showed that amorphigenin protected the LPS-induced bone loss. We concluded that amorphigenin can prevent inflammation-induced bone loss. Thus we expect that amorphigenin could be a treatment option for bone erosion caused by inflammation.
Bone Marrow ; Down-Regulation ; Femur ; Inflammation ; Macrophages ; NF-kappa B ; Osteoclasts ; Osteoporosis ; Rotenone ; T-Lymphocytes

BACKGROUND: IgA nephropathy (IgAN) is the most frequent primary glomerulonephritis in the world. Despite 20 years of research into this condition, much remains unknown about its pathogenesis and therapy. One major problem is that the prognostic evaluation and renal survival of IgAN is unreliable. METHODS: A retrospective study was performed to clarify the prognostic factors and the long-term renal survival rates of this disease. RESULTS: One hundred fifty-two patients with IgAN who followed-up at least 3 years after renal biopsy were included in this study. During a mean followed-up of 9.3 years after their renal biopsy (range:36-215 months), 33 of them (21.7%) had progressed to end-stage renal disease (ESRD). The actuarial renal survival rate was 97% at 5 years, and 85% at 10 years. Using univariate analysis, 5 risk factors for developing ESRD were identified:male sex, hypertension, heavy proteinuria, renal insufficiency at the time of biopsy, severe histopathologic findings such as subclass IV/V lesions by Haas' subclassification were associated with significant risk factors for developing ESRD. In multivariate regression analysis, only Haas' subclass IV/V lesions and renal insufficiency at the time of biopsy were the independent prognostic factors of IgAN. CONCLUSION: In conclusion, further long-term prospective study with larger number of patients would be necessary to assess the prognostic factors in IgAN.
Biopsy ; Glomerulonephritis ; Glomerulonephritis, IGA ; Humans ; Hypertension ; Immunoglobulin A* ; Kidney Failure, Chronic ; Prognosis* ; Proteinuria ; Renal Insufficiency ; Retrospective Studies ; Risk Factors ; Survival Rate

PURPOSE: Renal tubular aicdosis (RTA) is a disorder of renal acidification out of porportion to the reduction in glomerular filtration rate. Type IV RTA refers to hyperkalemic metabolic acidosis resulting from aldosterone deficiency or resistance. The incidence of each type RTA has not been reported exactly, however reports on type IV RTA have been recently increasing. METHODS: A retrospective clinical analysis was performed in 50 patients with hyperkalemic distal renal tubular acidosis diagnosed between Jan. 1984 and Feb. 2003 at Department of Internal Medicine, Keimyung University, Dongsan Medical Center. RESULTS: From 1984 to 2003, 50 cases of hyperkalemic distal renal tubular acidosis were diagnosed. The mean age was 50.8+/-19.5 years. The two most common conditions were posttransplantation (28%), and diabetes mellitus (22%), which were followed by hypertension (12%), systemic lupus erythematosus (12%), chronic renal failure (12%), and others (26%). Asymptomatic hyperkalemia (34%), and muscle weakness (28%) were the two most common clinical presentations. All patients demonstrated normal anion gap acidosis with positive urine anion gap. The mean creatinine clearance was 25.6+/-16.4 mL/min. The mean baseline PRA and aldosterone levels were 3.82+/-7.16 ng/mL/hr and 110.02+/-108.2 ng/mL, respectively. Hyperkalemia was well responded to 9-alpha-fludrocortisone, furosemide, K-exchane resin, and combinations of these regimens. CONCIUSION: Type IV RTA is the most common type of RTA in children and adults, and can be an important cause of asymptomatic hyperkalemia. Therefore, type IV RTA should be included in the diffrential diagnosis of unexplained hyperkalemia in various clinical settings.
Acid-Base Equilibrium ; Acidosis ; Acidosis, Renal Tubular* ; Adult ; Aldosterone ; Child ; Creatinine ; Diabetes Mellitus ; Diagnosis ; Furosemide ; Glomerular Filtration Rate ; Humans ; Hyperkalemia ; Hypertension ; Hypoaldosteronism ; Incidence ; Internal Medicine ; Kidney Failure, Chronic ; Lupus Erythematosus, Systemic ; Muscle Weakness ; Retrospective Studies

PURPOSE: We examined the clinical characteristics and incidence of adults idiopathic nephrotic syndrome (NS) according to pathologic diagnosis, age, sex. METHODS: We retrospectively reviewed the clinical and pathological characteristics of primary glomerular lesions in adults idiopathic NS taken a renal biopsy from 1978 to 2005 at the Dongsan Medical Center. We compared the prevalence of adults idiopathic NS according to the pathologic diagnosis between two time intervals 1978 to 1990 and 1991 to 2005. RESULTS: The patients had mean age of 36.7+/-16.3 years and male to female ratio was 1.7:1 with male predominance. The frequency of histopathologic diagnoses were minimal change nephrotic syndrome (MCNS) 51.6%, membranous glomerulonephritis (MGN) 21.3%, focal segmental glomerulosclerosis (FSGS) 12.1%, IgA nephropathy 9.1%, membranoproliferative glomerulonephritis (MPGN) 4.2% in decreasing order of frequency. The mean age was youngest in MCNS (32.9+/-15.1) and oldest in MGN (46.2+/-16.6). Between 1978 to 1990 period and 1991 to 2005 period, the prevalence of MGN was significantly increased, whereas the prevalence of MPGN was decreased significantly. The prevalence of MCNS had a tendency to decrease and that of IgA nephropathy had a tendency to increase, however, both didn't reach statistical significance. The incidence of FSGS didn't show a significant change during the both study periods. CONCLUSION: MCNS was the most common disease among adults idiopathic NS. MGN was the most frequent etiology in patients older than 45 years. The incidence of MGN was increased over the 28-year period, and that of MPGN decreased significantly. There was no change in the frequency of FSGS.
Adult* ; Biopsy ; Diagnosis ; Female ; Glomerulonephritis, IGA ; Glomerulonephritis, Membranoproliferative ; Glomerulonephritis, Membranous ; Glomerulosclerosis, Focal Segmental ; Humans ; Incidence ; Korea* ; Male ; Nephrosis, Lipoid ; Nephrotic Syndrome* ; Prevalence ; Retrospective Studies

Posttransplant lymphoproliferative disorder (PTLD) is an uncommon but life-threatening complication of immunosuppressive therapy following solid organ transplantation. It encompasses a heterogeneous group of lymphoproliferative disorders ranging from reactive, polyclonal hyperplasia to aggressive non- Hodgkin's lymphoma. The majority of PTLD is of B-cell origin and associated with Epstein-Barr virus (EBV) infection. Gastrointestinal involvement, especially small bowel and colon, is common in patients with PTLD, but the duodenum is rarely involved. We have experienced a case of PTLD involving the duodenum eight years after kidney transplantation in 50-year-old man. Two weeks before admission, he had complained of epigastric pain, and was diagnosed as pangastritis and duodenal ulcer by upper gastrointestinal endoscopy. He was admitted due to aggravated epigastric pain despite anti-ulcer medication. On the seventh hospital day, we found a new mass-like lesion in the pyloric area of antrum and diffuse ulceration in the duodenum by follow-up endoscopy. Histologic findings revealed diffuse large B-cell lymphoma. During reduction in immunosuppressive regimens, his conditions deteriorated rapidly. He died of sepsis associated with duodenal ulcer perforation, 18 days after diagnosis.
B-Lymphocytes ; Colon ; Diagnosis ; Duodenal Ulcer ; Duodenum* ; Endoscopy ; Endoscopy, Gastrointestinal ; Follow-Up Studies ; Herpesvirus 4, Human ; Hodgkin Disease ; Humans ; Hyperplasia ; Kidney Transplantation* ; Kidney* ; Lymphoma, B-Cell ; Lymphoproliferative Disorders* ; Middle Aged ; Organ Transplantation ; Sepsis ; Transplants ; Ulcer

BACKGROUND: Peritoneal solute transport rate, assessed by PET, varies widely among patients and has been shown to differ significantly among different ethnic groups. The aim of the present study is to investigate the peritoneal transport characteristics in Korean peritoneal dialysis (PD) patients and factors that predict peritoneal transport status. METHODS: Between May 2001 and February 2006, 141 patients on PD performed a standard 4-hour PET within the first 6 months after initiation of PD therapy. RESULTS: Of these 141 patients, there were 71males and 70 females. The mean age of the patients was 51.2+/-12.5 years and the etiology of renal failure was diabetes in 67 patients (47.5%). The mean 4-hour D/P creatinine ratio was 0.68+/-0.11. Compared with a mean of 0.65+/-0.15 as determined by Twardowski et al, our patients have significantly higher mean solute transport rate (p<0.05). Numbers of low (L), low-average (LA), high-average (HA), and high (H) transporters were 15 (10.6%). 68 (48.2 %), 53 (37.6%) and 5 (3.5%), respectively. However, according to our own data, the number of L, LA, HA and H were 18 (12.8%), 42 (29.8%), 64 (45.4%) and 17 (12.1%), respectively, significantly different from those classified by Twardowski et al. In univariate analysis, older age, hypoalbuminemia and lower BMI were predictive of high transport status. Using multiple linear regression, only hypoalbuminemia was independently predictive of higher 4-hour D/Pcr (p=0.000). CONCLUSION: Korean PD patients have a higher mean solute transport rate than Twardowskis data, and serum albumin is an independent predictor of high transport status. Further prospective studies with a large number of patients are needed for evaluating the diversity of peritoneal transport characteristics in different ethnic populations.
Female ; Male ; Humans

BACKGROUND: Peritoneal solute transport rate, assessed by PET, varies widely among patients and has been shown to differ significantly among different ethnic groups. The aim of the present study is to investigate the peritoneal transport characteristics in Korean peritoneal dialysis (PD) patients and factors that predict peritoneal transport status. METHODS: Between May 2001 and February 2006, 141 patients on PD performed a standard 4-hour PET within the first 6 months after initiation of PD therapy. RESULTS: Of these 141 patients, there were 71males and 70 females. The mean age of the patients was 51.2+/-12.5 years and the etiology of renal failure was diabetes in 67 patients (47.5%). The mean 4-hour D/P creatinine ratio was 0.68+/-0.11. Compared with a mean of 0.65+/-0.15 as determined by Twardowski et al, our patients have significantly higher mean solute transport rate (p<0.05). Numbers of low (L), low-average (LA), high-average (HA), and high (H) transporters were 15 (10.6%). 68 (48.2 %), 53 (37.6%) and 5 (3.5%), respectively. However, according to our own data, the number of L, LA, HA and H were 18 (12.8%), 42 (29.8%), 64 (45.4%) and 17 (12.1%), respectively, significantly different from those classified by Twardowski et al. In univariate analysis, older age, hypoalbuminemia and lower BMI were predictive of high transport status. Using multiple linear regression, only hypoalbuminemia was independently predictive of higher 4-hour D/Pcr (p=0.000). CONCLUSION: Korean PD patients have a higher mean solute transport rate than Twardowskis data, and serum albumin is an independent predictor of high transport status. Further prospective studies with a large number of patients are needed for evaluating the diversity of peritoneal transport characteristics in different ethnic populations.
Female ; Male ; Humans