BACKGROUND: To determine the molecular structure of type II collagen-specific T-cell receptors associated with rheumatoid arthritis (RA). METHODS: We generated CII-specific T-cell lines of 8 RA patient s by prolonged in vitro culture with bovine CII (bCII) and the immunogenic peptide (256-270) of human CII. The proliferation response towards CII stimulation was measured from the uptake of 3 H-thymidine. Changes in the secretion of Th 1 and Th2 cytokines in the culture supernatent were measured by ELISA. The TCR clonotypes of these T-cells were examined by RT-PCR/ SSCP analyses of all 22 V beta chains. RESULTS: T-cells from patients' tissue exhibited strong proliferation index upon CII stimulation, which was maintained up to 6 months in the culture. The secretion of INF-gamma from these T-cells increased along with the duration of culture time, while the amount of IL-4 production did not show significant changes. The SSCP band patterns of patients' T-cells appear as discrete bands unlike the smeary streak produced from normal samples. Some SSCP bands, each representing selected expansion of a TCR containing certain subtype of V beta peptides, appeared to be identical in more than one patients. Among these, the expansion of SSCP band representing the V beta 14 CDR3 region persisted after switching the antigen to the immunogenic human peptide (256-270). CONCLUSION: CII-reactive T-cells expressing distinct CDR3 motifs are selectively expanded in the peripheral blood and synovial fluid of RA patients, and their persistent proliferation upon CII stimulation, as well as the production Th 1-type cytokines, may play pivotal roles in RA pathogenesis.
Arthritis, Rheumatoid* ; Cytokines ; Enzyme-Linked Immunosorbent Assay ; Humans ; Interleukin-4 ; Molecular Structure ; Peptides ; Polymorphism, Single-Stranded Conformational ; Receptors, Antigen, T-Cell ; Synovial Fluid ; T-Lymphocytes*

Since the 1970s, the average life expectancy of Koreans has been increasing. Our concerns are not simply about longevity, but also about disability-free life. lately, Sasang constitutional medicine has attracted public attention, especially with respect to the elderly. The purpose of this study was to investigate the food habits, nutrients intake, and disease distribution among the elderly, according to their Sasang constitutions. The results are as follow : The distribution of constitutions of the subjects were Tae-eum 48.8%, So-yang 27.4%, So-eum 22.6%, and So-yang + So-eum 1.2%. In both elderly men and women, body weight, percent ideal body weight, and diastolic pressure of the Tae-eum were significantly higher than those of other constitutions. In both men and women, the level of hemoglobin in the Tae-eum was significantly higher than those of other constitutions. The level of LDL-cholesterol was higher, and the level of HDL-cholesterol was lower in the So-eum elderly women. Food habits of the So-eum were the most irregular, and nutrients intake of the So-eum was lower than that of other constitutions in both elderly men and women. In elderly men, the incidence of hypertension was the highest in the Tae-eum, and the incidence of gastritis was the highest in both So-yang and So-eum. In elderly women, the incidence of fatty liver was the highest in the Tae-eum and So-yang, and gastritis and hypertension were the highest in the So-eum. In the elderly, obese and anemic persons were significantly more in the Tae-eum and the So-eum, respectively. The results of this study showed that there were significant differences of physical, characeristics, food, habits, and distributions of disease for the subjects according to each Sasang constitutions. Intake of nutrient was poor, regardless of Sasang constitutions, in both men and women.
Aged* ; Blood Pressure ; Body Weight ; Constitution and Bylaws* ; Fatty Liver ; Female ; Food Habits* ; Gastritis ; Humans ; Hypertension ; Ideal Body Weight ; Incidence ; Life Expectancy ; Longevity ; Male

PURPOSE: It is known that single umbilical artery is frequently associated with gastrointestinal or urogenital anomaly, however, routine renal sonography has been debated in healthy neonate with isolated single umbilical artery. This study is designed to determine the usefulness of routine renal sonography in apparently healthy infants with an isolated single umbilical artery. METHODS: Thirty healthy neonates with a single umbilical artery without a major anomaly from January 1995 to July 2002 were enrolled. The authors investigated the clinical background of babies and their mothers after renal sonography after 72 hours of age. When the abnormalities were found at the first renal sonography, the severity of hydronephrosis and degree of obstruction and renal function were analyzed by follow up renal sonography, voiding cystourethrography(VCUG) and technetium-99m-dimercaptosuccinic acid(DMSA) scan or technetium-99m-mercaptoacetyl-triglycerine (MAG3) scan. RESULTS: Among the 30 healthy patients with isolated single umbilical artery, five patients(16.7%) showed abnormalities on first renal sonography with one major(3.3%) and four(13.4%) minor renal anomaly(minimal or mild hydroneohrosis). One major renal anomaly(severe hydronephrosis) showed severe decreased renal function on MAG3 scan without reflux, and the other four minor regressed spontaneously on follow up study. CONCLUSION: The value of routine early renal sonograpy for detecting renal anomaly in healthy infants with an isolated single umbilical artery remained unclear because most of the anomalies would regress spontaneously in the follow up study.
Follow-Up Studies ; Humans ; Hydronephrosis ; Infant* ; Infant, Newborn ; Mass Screening* ; Mothers ; Single Umbilical Artery*

Although rheumatoid arthritis has been known to be a common autoimmune disease characterized by chronic inflammation mainly evident in diarthrodial joints, its pathogenesis remains to be clarified. In the present study, to investigate the pathogenic signaling system taken place in the rheumatoid joints, we assessed whether synovial fluid obtained from patients with rheumatoid arthritis contains inducers for proinflammatory cytokines such as interleukin (IL)-12 and IL-23. Peritoneal macrophages isolated from IL-12/IL-23 p40-YFP reporter mice were stimulated with synovial fluid, followed by flow cytometry to screen CD11b+ and YFP-expressing cells, reflective of IL-12/IL-23 p40-producing macrophages. The expression levels of Toll-like receptor (TLR)-2 and -4, which have a potential to mediate IL-12/IL- 23 p40 induction, were determined in synovial cells obtained from a patient with rheumatoid arthritis by RT-PCR analyses. One out of 10 synovial fluid from rheumatoid arthritis patients induced IL-12/IL-23 p40 expression, while all of 10 synovial fluid from osteoarthritis patients did not. Synoviocytes constitutively expressed Toll-like receptor (TLR)-2 and -4 which are candidate receptors for IL-12/IL-23 inducers. Upon LPS stimulation, the levels of TLR-2 and -4 were downregulated and upregulated, respectively. Taken together, these results suggest that some patients with rheumatoid arthritis elicit synovitis through TLR-2- and -4-mediated induction of proinflammatory cytokines IL-12 and IL-23.
Animals ; Arthritis, Rheumatoid ; Autoimmune Diseases ; Cytokines ; Flow Cytometry ; Fluorescence* ; Humans ; Inflammation ; Interleukin-12 ; Interleukin-23 ; Interleukins ; Joints ; Macrophages ; Macrophages, Peritoneal ; Mass Screening* ; Mice* ; Osteoarthritis ; Synovial Fluid* ; Synovitis ; Toll-Like Receptors

PURPOSE: To guarantee the proper tension of the tape, we have adopted standardized methods by using Babcock clamp. MATERIALS AND METHODS: Medical records of 118 women who underwent Tension-Free Vaginal Tape Obturator (TVTO) prucedure were retrospectively reviewed. Tension of the tape was controlled either by holding the 1 cm length of the mesh with Babcock clamp in 72 cases (Group I), or by placing Metzenbaum scissor between the tape and the urethra in 46 cases (Group II) before pulling on the tape. The preoperative evaluations included symptom questionnaire, history taking, physical examination, one hour pad test and complete multichannel urodynamic study. Postoperatively, uroflowmetry, postvoiding residual urine volume and symptom questionnaire were repeated. RESULTS: The success rates of the operation were not different between groups. However, postoperative complication rates, including persistent pain and de novo urgency, in the Group II (n=9, 19.6%) was higher than in Group I (n=6, 8.3%). The rate of postoperative transient urinary retention was also higher in Group II (p<0.05). The rate of the patients who answered [satisfied] were significantly high in Group I (95.8%) compared to Group II (80.4%). CONCLUSIONS: By using the Babcock clamp technique, the complications can be minimized, and satisfaction increased. Our findings suggest that this technique does assure the proper tension for the normal voiding postoperatively.
Female ; Humans ; Medical Records ; Physical Examination ; Postoperative Complications ; Surveys and Questionnaires ; Retrospective Studies ; Suburethral Slings* ; Surgical Instruments ; Urethra ; Urinary Retention ; Urodynamics

Microalbuminuria is a marker of generalized endothelial dysfunction resulting from arterial stiffness or insulin resistance, and brachial-ankle pulse wave velocity (baPWV) is a good measure of arterial stiffness. We aimed to investigate whether elevated baPWV is independently associated with microalbuminuria. This study included 1,648 individuals aged over 40 who participated in the baseline Multi-Rural Cohort Study conducted in Korean rural communities between 2005 and 2006. Participants were classified into less than 30 mg/g as normoalbuminuria or 30-300 mg/g as microalbuminuriausing urinary albumin creatinine ratio (UACR). The median and Q1-Q3 baPWV values were significantly higher in the microalbuminuric group both in men (1,538, 1,370-1,777 cm/s vs. 1,776, 1,552-2,027 cm/s, P < 0.001) and women (1,461, 1,271-1,687 cm/s vs. 1,645, 1,473-1,915 cm/s, P < 0.001). BaPWV was independently associated with microalbuminuria in both genders after adjusting for pulse rate; fasting blood glucose; triglyceride; homeostatic model assessment insulin resistance (HOMA(IR)) and, history of hypertension and diabetes. Fasting blood sugar and HOMA(IR) were judged as having nothing to do with multicolinearity (r = 0.532, P < 0.001). Elevated baPWV was independently associated with microalbuminuria regardless of insulin resistance among rural subjects over 40 yr.
Adult ; Aged ; Albuminuria/*diagnosis/etiology/metabolism ; Ankle Brachial Index ; Ankle Joint/*physiopathology ; Blood Chemical Analysis ; Blood Glucose/analysis ; Brachial Artery/*physiopathology ; Cohort Studies ; Diabetes Mellitus, Type 2/complications/diagnosis ; Female ; Humans ; Hypertension/complications/diagnosis ; Male ; Middle Aged ; *Pulse Wave Analysis ; Risk Factors ; *Rural Population ; Serum Albumin/analysis ; Triglycerides/blood ; Vascular Stiffness

Indoleamine 2,3-dioxygenase (IDO) is a key negative regulator of immune responses and has been implicated in tumor tolerance, autoimmune disease and asthma. IDO was detected in the joint synovial tissue in the inflammatory microenvironment of rheumatoid arthritis (RA), but IDO expression in joint synovial tissue is not sufficient to overcome the inflamed synovial environment. This study aimed to unravel the mechanisms involving the failure to activate tolerogenic IDO in the inflamed joint. We demonstrate that both poly (I:C) and lipopolysaccharide (LPS) induce expression of IDO in synovial fibroblasts. However, inflammatory cytokines such as IL-17, TNF-alpha, IL-12, IL-23 and IL-16 did not induce IDO expression. Poly (I:C) appeared to induce higher IDO expression than did LPS. Surprisingly, toll-like receptor (TLR)4-mediated IDO expression was upregulated after depletion of myeloid differentiation primary response protein 88 (MyD88) in synovial fibroblasts using small interfering RNA (siRNA). IDO, TLR3 and TLR4 were highly expressed in synovial tissue of RA patients compared with that of osteoarthritis patients. In addition, RA patients with severe disease activity had higher levels of expression of IDO, TLR3 and TLR4 in the synovium than patients with mild disease activity. These data suggest that upregulation of IDO expression in synovial fibroblasts involves TLR3 and TLR4 activation by microbial constituents. We showed that the mechanisms responsible for IDO regulation primarily involve MyD88 signaling in synovial fibroblasts, as demonstrated by siRNA-mediated knockdown of MyD88.
Adaptor Proteins, Vesicular Transport/genetics/metabolism ; Arthritis, Rheumatoid/*metabolism ; Blotting, Western ; Cells, Cultured ; Fibroblasts/drug effects/*metabolism ; Humans ; Immunohistochemistry ; Indoleamine-Pyrrole 2,3,-Dioxygenase/genetics/*metabolism ; Interleukin-12/pharmacology ; Interleukin-16/pharmacology ; Interleukin-17/pharmacology ; Interleukin-23/pharmacology ; Lipopolysaccharides/pharmacology ; Myeloid Differentiation Factor 88/genetics/*metabolism ; Poly I-C/pharmacology ; Polymerase Chain Reaction ; RNA, Small Interfering/genetics/physiology ; Synovial Membrane/*cytology ; Toll-Like Receptor 4/genetics/metabolism ; Tumor Necrosis Factor-alpha/pharmacology

Inflammatory mediators has been recognized as an important role in the pathogenesis of rheumatoid arthritis (RA). IL-17 is increasingly recognized as an important regulator of immune and inflammatory responses, including induction of proinflammatory cytokines and osteoclastic bone resorption. Evidence of the expression and proinflammatory activity of IL-17 has been demonstrated in RA synovium and in animal models of RA. However, the signaling pathways that regulate IL-17 production remain unknown. In the present study, we investigated the role of the phosphatidylinositol 3 kinase (PI3K)-Akt pathway in the regulation of IL-17 production in RA. PBMC were separated from RA (n=24) patients, and stimulated with various agents (anti CD3, anti CD28, PHA, ConA, IL-15). IL-17 levels were determined by sandwich ELISA and RT-PCR. The production of IL-17 was significantly increased in cells treated with anti-CD3 antibody, PHA, IL-15 or MCP-1 (P<0.05). ConA also strongly induced IL-17 production (P<0.001), whereas TNF-alpha, IL-1beta, IL-18 or TGF-beta did not. IL-17 was detected in the PBMC of patients with osteoarthritis (OA) but their expression levels were much lower than those of RA PBMC. Anti-CD3 antibody activated the PI3K-Akt pathway and activation of the PI3K-Akt pathway resulted in a pronounced augmentation of nuclear factor kappaB (NF-kappaB). IL-17 production by activated PBMC in RA is completely or partially blocked in the presence of NF-kappaB inhibitor PDTC and PI3K- Akt inhibitor, wortmannin and LY294002, respectively. Whereas the inhibition of AP-1 and extracellular signal-regulated kinase (ERK)1/2 did not affect IL-17 production. These results provide new insight into that PI3K/Akt and NF-kappaB dependent signal transduction pathway could be involved in the overproduction of key inflammatory cytokine, IL-17 in rheumatoid arthritis.
Arthritis, Rheumatoid* ; Bone Resorption ; Cytokines ; Enzyme-Linked Immunosorbent Assay ; Humans ; Interleukin-15 ; Interleukin-17* ; Interleukin-18 ; Models, Animal ; NF-kappa B ; Osteoarthritis ; Osteoclasts ; Phosphatidylinositol 3-Kinase ; Phosphotransferases ; Signal Transduction* ; Synovial Membrane ; Transcription Factor AP-1 ; Transforming Growth Factor beta ; Tumor Necrosis Factor-alpha

OBJECTIVE: Hydroxychloroquine (HCQ) is a drug that has been used to treat autoimmune disorders such as rheumatoid arthritis and systemic lupus erythematosus. However, the specific mechanism for its pharmacologic action has been largely unknown. It has been reported that dysregulation of lymphocytic apoptosis mediated by Fas ligand (FasL) and Fas is associated with the development of autoimmune diseases and HCQ induces apoptosis in peripheral blood lymphocytes. These reports suggest that HCQ may exert its pharmacologic effects through the modulation of FasL and Fas. Therefore, we are intended to investigate the effects of HCQ on the regulation of FasL and Fas. Jurkat cells or peripheral blood mononuclear cells (PBMNC) were treated with varying concentrations of HCQ. Semiquantative reverse transcription- polymerase chain reaction, Western blotting, flow cytometry, and ELISA were used for this study. HCQ at nontoxic concentrations( 50~150 micrometer) caused a dose dependent increase of FasL mRNA expression and FasL in cell lysates. HCQ inhibited the release of intracellular 40 kDa FasL by Jurkat cells which were pulse-stimulated with PHA (50 microgram/ml). Jurkat cells activated with PHA increased membrane bound FasL (mFasL) expression (24.5+/-4.3%), however Jurkat cells pretreated with HCQ(150 micrometer) followed by PHA administration did not further increase mFasL expression (26.8+/-1.6%). Addition of different concentrations of HCQ to the cultured PBMNC stimulated with PHA for 24 hours showed increase of soluble FasL (sFasL). The levels of sFasL treated with HCQ zero, 50, 150 and 300 micrometer for 24 hours were 38.6+/-3.0, 43.4+/-5.1, 77.0+/-3.6(P<0.05) and 72.3+/-8.1pg/ml(P<0.05) respectively. However, fas metabolism was not affected by HCQ. CONCLUSION: These results suggest that HCQ may exhibit its pharmacological effects by upregulation of FasL gene expression and increased production sFasL without any influence on the Fas metabolism of T cells.
Apoptosis ; Arthritis, Rheumatoid ; Autoimmune Diseases ; Blotting, Western ; Enzyme-Linked Immunosorbent Assay ; Fas Ligand Protein* ; Flow Cytometry ; Gene Expression ; Humans ; Hydroxychloroquine* ; Jurkat Cells ; Lupus Erythematosus, Systemic ; Lymphocytes ; Membranes ; Metabolism* ; Polymerase Chain Reaction ; RNA, Messenger ; T-Lymphocytes* ; Up-Regulation

A 13-year-old girl presented with multiple skin abscesses. She was diagnosed as having juvenile dermatomyositis (DM) at the age of 7 years. She had suffered from recurrent skin infections, atypical pruritic dermatitis and pneumonia since the age of 8 years. Bacteriologic and fungal cultures for skin abscesses and oral mucosa were positive S. aureus and C. albicans, respectively. Chemotactic defect in peripheral blood neutrophils was observed. The level of serum IgE was markedly elevated, and anti-S.aureus specific IgE was found. A diagnosis of hyperimmunoglobulin E-recurrent infection syndrome (HIE) was made and she was successfully treated with surgical drainage and antibiotics. To our knowledge, this is the first case report of HIE in a patient with juvenile dermatomyositis.
Adolescence ; Case Report ; Dermatomyositis/complications* ; Female ; Human ; IgE/blood ; Job's Syndrome/immunology ; Job's Syndrome/diagnosis ; Job's Syndrome/complications* ; Staphylococcal Infections/immunology ; Staphylococcal Infections/complications ; Staphylococcus aureus/immunology