beta-amyloid peptide (Abeta) consisting of 40 to 42 amino acid is the principle constituent of senile plaques in Alzheimer's disease. Although, the hypothesis that deposition of AP triggers a cascade of events leading to the pathology of Alzheimer's disease has been widely accepted, direct evidence for triggering accumulation of phosphorylated tau in paired helical filament is rare. In this study, we examined neurotoxicity induced by 3 kinds of beta-amyloid peptides 1 ~28, 25~,35 and 1~40 to elucidate the way of mechanism trading to neuronal cell death caused by Abeta using cultured hippocampal neurons. For this purpose, we measured lactate dehydrogenase (LDH) in the culture media after treatment with Abeta combined with anti-oxidant drug, trolox, or not. By histochemical and TUNEL method, we studied the change of immunoreaction to anti-MAP-2 (microtubule associated protein -2, the main component of neuritis) and detected apoptotic cells, respectively, in the hippocampal neurons treated with Abeta. To investigate whether tau phosphorylation involve neurotoxicity induced by Abeta, we immunostained the neurons with anti-SMI-31 to recognize phosphorylated Ser 396/404 of tau. From our data, we suggested that Abeta1-40 and Abeta25-35 induced marked neurodegenerative changes, and the mechanism responsible for cell death caused by Abeta -neurotoxicity was associated with the apoptosis. Because Abeta-neurotoxicity was not inhibited by anti-oxidant, trolox, we suggested that anti-oxidant did not protect the neuronal cells against the damage induced by Abeta in ou. expo.imental envi.onment. Finally, we suggested that AP treatment did not potentiate the immunoreactivity to anti-phosphorylated tau antibody and we speculated that Abeta-neurotoxicity led hippocampal cells to apoptosis without tau phosphorylation.
Alzheimer Disease ; Apoptosis* ; Cell Death ; Culture Media ; In Situ Nick-End Labeling ; L-Lactate Dehydrogenase ; Neurons* ; Pathology ; Peptides* ; Phosphorylation* ; Plaque, Amyloid

PURPOSE: In order to evaluate the spectrum of mitochondrial DNA (mtDNA) mutations in the patients with suspected Leber's hereditary optic neuropathy (LHON). METHODS: We investigated 14 primary mtDNA mutations at nucleotide positions (nps 3460A, 4160C, 5244A, 9101C, 9804A, 10663C, 11778A, 13730A, 14459A, 14482G, 14484C, 14495G, 14498T, and 14568T) and one common secondary mutation (np15257A) in 82 Korean patients with suspected LHON. RESULTS: Among them, only three kinds of LHON mutations were identified in 60 (73%) of 82 probands, which were comprised of 46 (56%) cases with the 11778A, 13 (16%) with the 14484C, and 1 (1%) with the 3460A. None of the other mtDNA mutations was detected. Of the 60 probands with LHON positive mutations, 19 (32%) had relevant family histories. Heteroplasmy was determined in 2 (4%) of the 46 probands with the 11778A and 1 (8%) of 13 probands with the 14484C. CONCLUSIONS: In conclusion, the 11778A was the most common cause (56%), and higher prevalence of the 14484C and the lower prevalence of the 3460A were characteristic in Korean patients with LHON. Especially, the 3460A had a remarkable racial difference compared with Caucasians. Except 3460A, 11778A, and 14484C, the other mutations screened may not be involved in pathogenesis and not have a synergistic effect on the clinical expression of LHON in Koreans.
Asian Continental Ancestry Group ; DNA, Mitochondrial* ; Humans ; Molecular Biology* ; Optic Atrophy, Hereditary, Leber* ; Prevalence

Leber's hereditary optic neuropathy (LHON) is a maternally transmitted disease causing acute or subacute, bilateral optic atrophy mainly in young men. It is found to be a mitochondrial disorder with the primary mitochondrial DNA (mtDNA) mutations at 11778, 3460, and 14484. The incidence of each mutation is reported to be race-dependent. Point mutations at mtDNA nucleotide position 11778 and 14484 have been reported in Korean patients with LHON, however there has been no report of mtDNA mutation at nucleotide position 3460. Molecular genetic analyses at four primary sites (11778, 14484, 15257, and 3460) of mitochondrial DNA using the polymerase chain reaction, restriction enzyme digestion, and direct sequencing were performed in a 35-yr-old man with severe visual loss. A point mutation in the mtDNA at nucleotide position 3460 was identified and a conversion of a single alanine to a threonine was confirmed. To our knowledge, this is the first report confirming mtDNA mutation at nucleotide position 3460 in Korean patients with LHON. Detailed molecular analyses would be very helpful for the correct diagnosis of optic neuropathy of unknown etiology and for genetic counseling.
Adult ; *DNA, Mitochondrial ; Humans ; Male ; Optic Atrophy, Hereditary, Leber/*genetics ; *Point Mutation

OBJECTIVE: The purpose of this study was to investigate whether selective cyclooxygenase (COX) inhibitors promote paclitaxel-induced apoptosis in taxane-resistant ovarian cancer cells by suppressing MDR1/P-glycoprotein (P-gp) expression. METHODS: Taxane-resistant ovarian cancer cells were cultured with paclitaxel alone or combined with a selective COX inhibitors. The expression patterns of MDR1/P-gp and the ability of COX inhibitors to inhibit growth of taxane-resistant ovarian cancer cells were measured. The efficacy of prostaglandin E2 (PGE2) supplementation was measured to evaluate the mechanisms involved in suppressing MDR1 gene expression. RESULTS: P-gp was upregulated in taxane-resistant ovarian cancer cells compared to paired paclitaxel-sensitive ovarian cancer cells. An 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay showed that selective COX inhibitors significantly enhanced the cytotoxic effects of paclitaxel in taxane-resistant ovarian cancer cells via a prostaglandin-independent mechanism. These increased apoptotic effects were further verified by measuring an increased percentage of cells in sub-G1 stage using flow cytometry. Selective COX inhibitors suppressed MDR1 and P-gp expression. Moreover, combined treatment with paclitaxel and selective COX inhibitors increased poly (ADP-ribose) polymerase (PARP) cleavage in taxane-resistant ovarian cancer cells. CONCLUSION: Selective COX inhibitors significantly promote paclitaxel-induced cell death in taxane-resistant ovarian cancer cells in a prostaglandin-independent manner. COX inhibitors could be potent therapeutic tools to promote paclitaxel sensitization of taxane-resistant ovarian cancers by suppressing MDR1/P-gp, which is responsible for the efflux of chemotherapeutic agents.
Apoptosis ; Cell Death ; Cyclooxygenase Inhibitors ; Dinoprostone ; Flow Cytometry ; Ovarian Neoplasms ; P-Glycoprotein ; Paclitaxel ; Prostaglandin-Endoperoxide Synthases ; Tetrazolium Salts ; Thiazoles

PURPOSE: To evaluate the spectrum of mitochondrial DNA (mtDNA) aberrations in patients with suspected chronic progressive external ophthalmoplegia (CPEO) and to establish the molecular diagnostic method for CPEO in Koreans. METHODS: We performed mtDNA analyses for single deletions with long-range PCR and direct sequencing, and for the nine important point mutations including 3243A>G and 8344A>G with PCR/RFLP in muscles, bloods and paraffin-embedded muscle sections of 16 Korean patients with suspected CPEO. RESULTS: Three novel single mtDNA deletions were identified in three patients' muscles: 3159bp deletion from np 6657 to np 9815, 7591bp from np 8429 to np 16019, and 6191bp from np 7799 to np 13989. In addition, multiple mtDNA deletions were found in one patient. None of the blood specimen had mtDNA deletions even in the patients with mtDNA deletion in muscle. All single deletion junctions were flanked by direct repeats of 6-8 bp. None of the nine mtDNA point mutations were found in muscles, bloods or paraffin-embedded muscle sections. CONCLUSIONS: We identified three novel single deletions by mtDNA analyses in the muscles of 3 patients with CPEO. However, point mutations were not found. Furthermore, we established a molecular diagnostic method for CPEO in Korea. Long-range PCR and direct sequencing of the muscles were appropriate as a molecular diagnostic method for CPEO in Koreans.
Diagnosis* ; DNA, Mitochondrial* ; Humans ; Korea ; Muscles ; Ophthalmoplegia, Chronic Progressive External* ; Pathology, Molecular ; Point Mutation ; Polymerase Chain Reaction ; Repetitive Sequences, Nucleic Acid

Traumatic dislocation of the peroneus longus tendon is an often unrecognized injury which has been reported to occur most commonly during sports activity. Most acute cases with early detection can be treated by simple repair of the tendon or retinaculum using one of several procedures available. Accurate treatment through a comprehensive evaluation of the ankle injury prevents suboptimal and sometimes unrecorrectable outcomes. The authors experienced concomitantly the peroneus longus tendon dislocation associated with a trimalleolar fracture of the ankle. We report this case a brief review of the literature.
Animals ; Ankle ; Ankle Injuries ; Dislocations ; Sports ; Tendons

Pure-phase beta-tricalcium phosphate(beta-TCP) proved to be a bone regeneration material, providing the patient with vital bone at the defect site in a reasonable time, making a second surgical procedure for bone harvesting unnecessary. This study compares bone healing and BMP 2/4 expression in cranial defects in rabbits grafted with autogenous bone and beta-TCP. Thirty New Zealand White rabbits was divided into 3 group of 10 animals each. Bilateral calvarial defects were made in the parietal bones of each animal. beta-TCP placed in one defect and the other defects was filled with autogenous bone. The animal were sacrificed at 4, 8 and 12 weeks. Immunohistochemical analysis was used to investigate the expression of BMP 2/4. 1. The new bone formation around autogenous bone from 4 weeks and beta-TCP from 8 weeks. 2. In autogenous bone graft, BMP 2/4 expression was decreased from 4 to 12 weeks. 3. In beta-TCP graft, BMP 4 expression was increased from 8 to 12 weeks. But, BMP 2 was observed from 12 weeks. This study showed that bone healing, regeneration and, BMP 2/4 expression are delayed in grafted beta-TCP than autogenous bone.
Animals ; Bone Regeneration* ; Humans ; Osteogenesis ; Parietal Bone ; Rabbits ; Regeneration ; Transplants

PURPOSE: Hematopoietic cell transplantation (HCT) recipients are vulnerable to invasive infection by Haemophilus influenzae type b (Hib) and Streptococcus pneumoniae (Sp). This study was performed to evaluate immune responses after Hib and Sp vaccination in Korean pediatric HCT recipients. METHODS: Patients were prospectively enrolled at Samsung Medical Center during 2009-2011. ELISA tests to detect anti-PRP IgG antibody and antibodies to Sp serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F were performed at the Center for Vaccine Evaluation and Study, Ewha Medical Research Institute. RESULTS: Ten patients (two allogeneic, eight autologous recipients) with median age 5.4 years (range 2.7-12.2 years) were enrolled. Before Hib vaccination, 60% of patients' anti-PRP IgG titers were below 0.15 microg/mL. After vaccination, 100% of patients' anti-PRP IgG titers increased above 0.15 microg/mL (cut-off value for detection) and 1.0 microg/mL (cut-off value for seroprotection). For pneumococcus, in 2-5 year-old patients, pre-vaccination geometric mean concentrations (GMCs) of IgG for six serotypes (4, 6B, 9V, 14, 18C, and 23F) were below 0.35 microg/mL and at 5 months post-vaccination GMCs of IgG for all seven serotypes increased to above 0.35 microg/mL. In patients older than 5 years, pre-vaccination GMCs of IgG for four serotypes (4, 9V, 14, and 23F) were below 0.35 microg/mL and at 3 months post-vaccination GMCs of IgG for all seven serotypes increased to above 0.35 microg/mL. CONCLUSION: Most HCT recipients had low or no protective antibodies to Hib and Sp before vaccination, but showed good immune responses to protective levels after vaccination.
Academies and Institutes ; Antibodies ; Antibody Formation* ; Cell Transplantation* ; Enzyme-Linked Immunosorbent Assay ; Haemophilus influenzae type b* ; Humans ; Immunoglobulin G ; Prospective Studies ; Streptococcus pneumoniae* ; Transplants* ; Vaccination*

BACKGROUND: The purpose of our study was to evaluate the usefulness of hip arthroscopy including extensive capsulectomy for synovial chondromatosis of the hip. METHODS: From 2008 to 2016, 13 patients with synovial chondromatosis of the hip were treated with arthroscopic removal of loose bodies and synovectomy using three arthroscopic portals. An extensive capsulectomy was performed to allow the remaining loose bodies to be out of the extracapsular space, and the excised capsule was not repaired. All patients were assessed by clinical scores and the radiographs were reviewed to determine whether the remaining loose bodies disappeared at the last follow-up. RESULTS: Eight men and two women were followed up for a minimum of 1 year (mean, 3.8 years; range, 1 to 6.8 years) after hip arthroscopy. Clinical outcomes such as modified Harris hip score, University of California Los Angeles score, and Western Ontario and McMaster Universities Osteoarthritis Index score improved at the last follow-up. Although seven hips had remaining loose bodies after arthroscopic surgery, the remaining loose bodies disappeared in five hips (71.4%) at the last follow-up. CONCLUSIONS: Arthroscopic surgery was useful to treat synovial chondromatosis of the hip. In spite of limited removal of loose bodies, arthroscopic procedures including extensive capsulectomy could be effective for the treatment of synovial chondromatosis of the hip.
Arthroscopy* ; California ; Chondromatosis, Synovial* ; Female ; Follow-Up Studies ; Hip* ; Humans ; Male ; Ontario ; Osteoarthritis

Rheumatoid arthritis (RA) can cause significant hand and wrist damage and dysfunction. The aim of medical treatment is to eradicate inflammation and prevent damage to joints and soft tissues. Advances in newer biological therapies over the last two decades have resulted in greater remission rates and lower disease activity status. Despite these improvements, surgical intervention is still indicated in cases of disability, irreversible deformities, and severe pain. However, there are large variations in the surgical rates of common rheumatoid hand procedures, which may indicate clinical uncertainty or disagreement between treating rheumatologists and hand surgeons. In this review, we provide a basic overview of common problems of the hand and wrist in RA patients. The target audience is rheumatologists for their better understanding of surgical options and for better informed patient consultation before referring to hand surgeons.