OBJECTIVES: Controversial arguments exists on both the case for and against on the accumulation of mitochondrial DNA (mtDNA) deletion in association to tissue and age. The debate continues as to whether this mutation is a major contributor to the phenotypic expression of aging and common degenerative diseases or simply a clinical insignificant epiphenomenon. The objective of this study was to determine whether the accumulation of mtDNA deletion is correlated with age-related and tissue-specific variation. MATERIALS AND METHODS: One hundred and fifty-seven tissues from blood, ovary, uterine muscle, and abdominal muscle were obtained from patients ranging in age from 31~60 years. After reviewing the clinical reports, patients with mitochondrial disorder were excluded from this study. The tissues were obtained at gynecological surgeries with the consent of the patient. Total DNA isolated from blood, ovary, uterine muscle, and abdominal muscle was amplified by two rounds of PCR using two pairs of primers corresponding to positions 8225-8247 (sense), 13551-13574 (antisense) for the area around deleted mtDNA and 8421-8440 (sense), 13520-13501 (antisense) for nested PCR product. A statistical analysis was performed by c2-test. RESULTS: About 0% of blood, 94.8% of ovary, 71.4% of uterine muscle, and 86.1% abdominal muscle harbored mtDNA deletion. When we examined the proportion of deleted mtDNA according to age deletion rate was 90% of ovary, 63.6% of uterine muscle, 77.7% of abdominal muscle in thirties and 100% of all tissue in fifties. CONCLUSION: The findings of this study suggest that the mtDNA deletion is varied in tissue-specific pattern and increases with aging.
Abdominal Muscles ; Aging ; Animals ; DNA ; DNA, Mitochondrial* ; Female ; Gynecologic Surgical Procedures ; Humans ; Mice ; Mitochondrial Diseases ; Myometrium ; Ovary ; Polymerase Chain Reaction

BACKGROUND: Postpartum thyroiditis(PPT) is one of syndromes of thyroid dysfunction that occurs in the first year after parturition. Reported incidence of PPT is 3.9-8.2% of postpartum women in several studies from different countries. The fact that 52-100% of patients with PPT have thyroid autoantibodies, and that lymphocytic infiltration of thyroid gland is the characteristic pathological feature of PPT suggest that PPT is an autoimmune disease. High iodine intake in short term period is known to aggrevate the experimental autoimmune thyroiditis. This study was performed to investigate the incidence and clinical features of PPT in Korean postpartum women who usually ingest excessive amount of idine in immediate postpartum period and to investigate the predictive value of thyroid autoantibodies in the development of PPT in them. METHOD: Between March 1996 and February 1997, 99 women without previous history of any thyroid disease who delivered babies at Boramae hospital were enrolled. Thyroid function parameters(T3, T4, free T4, TSH), thyroid autoantibodies(anti-microsomal antibody, anti-thyroglobulin antibody) and urinary iodine excretion were measured prospectively before and 1, 3 months after delivery. Dietary iodine intake during postpartum period was evaluated by questionnaire, and clinical parameters were followed up. RESULTS: During 3 months of observation, PPT developed in 8.1%(8/99) of postpartum women. Five cases had typical course having thyrotoxic phase and the other 3 cases had hypothyroid phase without toxic phase. However, only one of those required thyroid hormone replacement therapy in the latter group. There were no differences in age, baseline thyroid function parameters, parity, percent cases with family history of thyroid disease between those developed PPT (n=8) and those did not develop PPT(n=91). Duration of high iodine intake(3.8 +- 0.5 wk. vs. 3.7 +- 0.8 wk., p>0.05), total ingested amount of high iodine diet(77 +- 28 vs. 79 +- 24 bowels of miyokguk, p)0.05), and the urinary iodine excretion(1.9 +- 1.4 mg/g creatinine vs. 3.7 +- 3.7mg/g creatinine, p0.05) at 1 month postpartum were not different between two groups. Of 99 total subjects, anti-microsomal antibody(AMA) was present in 13.1%(13/99) before delivery in their sera. Positive predictive value of the presence of AMA before delivery in predicting the development of PPT was 30.8%. CONCLUSION: The fact that incidence of PPT in normal Korean postpartum women who usually have high iodine intake in immediate postpartum period is not higher than those of other countries, and that there was no difference in the amount of iodine intake between those developed PPT and those did not suggest that high iodine intake in immediate postpartum period do not influence on the incidence of PPT. The presence of AMA before delivery had low specificity in prediction of development of PPT, so the measurement of AMA seems not to be a useful screening test.
Autoantibodies ; Autoimmune Diseases ; Creatinine ; Female ; Hormone Replacement Therapy ; Humans ; Incidence* ; Iodine* ; Mass Screening ; Parity ; Parturition ; Postpartum Period* ; Postpartum Thyroiditis* ; Prospective Studies ; Surveys and Questionnaires ; Sensitivity and Specificity ; Thyroid Diseases ; Thyroid Gland ; Thyroiditis, Autoimmune

Rheumatoid arthritis (RA) is a chronic inflammatiory disease that mainly destroys cartilages or bones at the joints. This inflammatory disorder is initiated by self-attack using own immune system, but the detail of pathological mechanism is unclear. Features of autoantigens leading to autoimmune disease are also under veil although several candidates including type II collagen have been suggested to play a role in pathogenesis. In this report, we tried to identify proteins responding to antibodies purified from RA patients and screen proteins up-regulated or down-regulated in RA using proteomic approach. Fibronectin, semaphorin 7A precursor, growth factor binding protein 7 (GRB7), and immunoglobulin mu chain were specifically associated with antibodies isolated from RA synovial fluids. In addition, some metabolic proteins such as adipocyte fatty acid binding protein, galectin-1 and apolipoprotein A1 precursor were overexpressed in RA synovium. Also, expression of peroxiredoxin 2 was up-regulated in RA. On the contrary, expression of vimentin was severely suppressed in RA synoviocytes. Such findings might give some insights into understanding of pathological mechanism in RA.
Synovial Fluid/metabolism ; Sepharose/chemistry ; Proteomics/methods ; Middle Aged ; Male ; *Inflammation ; Humans ; *Gene Expression Regulation ; Female ; Collagen Type II/biosynthesis ; Autoantigens/metabolism ; Arthritis, Rheumatoid/*metabolism ; Aged ; Adult

OBJECTIVE: Angiopoietin-1 (Ang1) is a potent angiogenic factor that can increase synovial angiogenesis and also enhance osteoblast maturation and bone formation. However, its role in rheumatoid arthritis (RA) has not been well documented. Thus, we investigated roles of Ang1 in collagen-induced arthritis (CIA). METHODS: A recombinant adenovirus carrying the gene that encodes either cartilage oligomeric matrix protein (AdCOMP)-Ang1 (a modified form of Ang1) or LacZ (AdLacZ) was injected intravenously into CIA mice. Clinical, radiological, histopathological, and immunofluorescent analyses were performed. Serum levels of receptor activators of nuclear factor kappaB ligand (RANKL) and osteoprotegerin (OPG) and expression of osteoblast maturation genes were analyzed. RESULTS: AdCOMP-Ang1-injected mice developed more severe inflammation than the AdLacZ-injected mice. However, there were no significant differences in cartilage damage and bone erosion. More PECAM-1-positive blood vessels were seen in the synovium of the AdCOMP-Ang1-injected mice than in those injected with AdLacZ. Interestingly, a lower number of TRAP-positive osteoclasts were observed in AdCOMP-Ang1-injected CIA mice than in the AdLacZ group when comparing sections obtained from joints showing similar synovial proliferation. The serum OPG/RANKL ratio and expression of osteoblast maturation genes, such as runt-related transcription factor 2, bone sialoprotein, type 1 collagen, osteopontin, and osterix, were significantly upregulated in the AdCOMP-Ang1 group. CONCLUSION: COMP-Ang1 facilitates arthritis onset and increases synovial inflammation, but enhances osteoblast maturation, which in turn inhibits osteoclastogenesis by increasing the OPG/RANKL ratio in CIA. Our results suggest that careful investigation is necessary to delineate the possible therapeutic use of COMP-Ang1 as an adjunctive agent, in combination with anti-inflammatory therapies, for the prevention of bone destruction in RA.
Adenoviridae ; Angiogenesis Inducing Agents ; Angiopoietin-1 ; Animals ; Arthritis ; Arthritis, Experimental ; Arthritis, Rheumatoid ; Blood Vessels ; Cartilage ; Collagen Type I ; Extracellular Matrix Proteins ; Glycoproteins ; Inflammation ; Integrin-Binding Sialoprotein ; Joints ; Lifting ; Mice ; Osteoblasts ; Osteoclasts ; Osteogenesis ; Osteopontin ; Osteoprotegerin ; Synovial Membrane ; Transcription Factors

BACKGROUND/AIMS: Biliary complication after orthotopic liver transplantation(OLT) continue to be a significant cause of surgical morbidity, occurring in 10~50% of patients. Bile duct obstruction and biliary leaks account for the majority of these complications. An end-to-end choledochocholedochostomy(CD) with or without T-tube or a Roux-en-Y choledochojejunostomy(CDJ) have been the standard methods of biliary reconstruction following OLT. We reviewed our experiences of OLT to assess whether or not use of the T-tube leads to increased biliary tract complications. MATERIALS AND METHODS: From May 1996 to Feb 1998, 34 consecutive liver transplantation in 33 patients were performed at our hospital, including 12 living related liver transplantaiton. Nineteen patients were male and twenty-two patients were adult. The main indication of OLT was hepatitis B virus related cirrhosis(14 cases)in adult and biliary atresia(7 cases) in child. Four ABO incompatible cases were included in living related liver transplant. Biliary tract complications were categorized as bile leak, stenosis, or obstruction that required therapeutic intervention. Retrospective review of clinical recordings and laboratory findings were done. The median follow up periods was 10 months(range: 3~24 month). RESULTS: The methods of biliary reconstruction in cadaveric liver transplant were CD with T-tube(n=2), CD without T-tube(n=18) and Roux-en-Y HJ(n=2), respectively. In living related liver transplant(LRLT), all 12 cases were reconstructed by Roux-en-Y CDJ without stent. Biliary tract complications were observed in one case of child LRLT patient that biliary fistula occurred at exposed bile duct on cut surface of liver. This patient underwent reoperation for constructed another HJ and progressed without complication. T-tube related complication was observed in one adult patient. T-tube was impinged at cystic duct that obstructed bile flow, intermittently. This patient was treated with insertion of PTBD catheter and removal of T-tube. No other biliary complications were detected in our series. CONCLUSION: Performing an end-to-end CD without T-tube was a safe and effective method of reconstructing the biliary tract following hepatic transplantation in adult patients, comparing with T-tube splintage method. We concluded that routine placement of the T-tube at hepatic transplantation was considered to some selective cases, but more large scale and long -term studies were needed.
Adult ; Bile Ducts* ; Bile* ; Biliary Fistula ; Biliary Tract ; Cadaver ; Catheters ; Child ; Cholestasis ; Constriction, Pathologic ; Cystic Duct ; Follow-Up Studies ; Hepatitis B virus ; Humans ; Liver Transplantation* ; Liver* ; Male ; Reoperation ; Retrospective Studies ; Stents

BACKGROUND/AIMS: Biliary complication after orthotopic liver transplantation(OLT) continue to be a significant cause of surgical morbidity, occurring in 10~50% of patients. Bile duct obstruction and biliary leaks account for the majority of these complications. An end-to-end choledochocholedochostomy(CD) with or without T-tube or a Roux-en-Y choledochojejunostomy(CDJ) have been the standard methods of biliary reconstruction following OLT. We reviewed our experiences of OLT to assess whether or not use of the T-tube leads to increased biliary tract complications. MATERIALS AND METHODS: From May 1996 to Feb 1998, 34 consecutive liver transplantation in 33 patients were performed at our hospital, including 12 living related liver transplantaiton. Nineteen patients were male and twenty-two patients were adult. The main indication of OLT was hepatitis B virus related cirrhosis(14 cases)in adult and biliary atresia(7 cases) in child. Four ABO incompatible cases were included in living related liver transplant. Biliary tract complications were categorized as bile leak, stenosis, or obstruction that required therapeutic intervention. Retrospective review of clinical recordings and laboratory findings were done. The median follow up periods was 10 months(range: 3~24 month). RESULTS: The methods of biliary reconstruction in cadaveric liver transplant were CD with T-tube(n=2), CD without T-tube(n=18) and Roux-en-Y HJ(n=2), respectively. In living related liver transplant(LRLT), all 12 cases were reconstructed by Roux-en-Y CDJ without stent. Biliary tract complications were observed in one case of child LRLT patient that biliary fistula occurred at exposed bile duct on cut surface of liver. This patient underwent reoperation for constructed another HJ and progressed without complication. T-tube related complication was observed in one adult patient. T-tube was impinged at cystic duct that obstructed bile flow, intermittently. This patient was treated with insertion of PTBD catheter and removal of T-tube. No other biliary complications were detected in our series. CONCLUSION: Performing an end-to-end CD without T-tube was a safe and effective method of reconstructing the biliary tract following hepatic transplantation in adult patients, comparing with T-tube splintage method. We concluded that routine placement of the T-tube at hepatic transplantation was considered to some selective cases, but more large scale and long -term studies were needed.
Adult ; Bile Ducts* ; Bile* ; Biliary Fistula ; Biliary Tract ; Cadaver ; Catheters ; Child ; Cholestasis ; Constriction, Pathologic ; Cystic Duct ; Follow-Up Studies ; Hepatitis B virus ; Humans ; Liver Transplantation* ; Liver* ; Male ; Reoperation ; Retrospective Studies ; Stents