Therapeutic Effect of a Recombinant betaig-h3 Fragment-RGD Peptide for Chronic Inflammatory Arthritis

OBJECTIVE: betaig-h3 is a 68kDa extracellular matrix protein which is overexpressed in synovial tissues of rheumatoid arthritis (RA). Previous results proved that betaig-h3 fragments are relevant to adhesion and migration of synovial fibroblast and angiogenesis through interaction with alphavbeta 3 integrin. We designed a recombinant betaig-h3 protein consisting of a fas-1 domain and RGD motif and evaluated the therapeutic efficacy in RA. METHODS: Inhibitory effect of adhesion and migration of NIH3T3 cell line was evaluated in 96 well microtiter and transwell plates coated with betaig-h3. Clinical arthritis index was evaluated after treating CIA mice with MFK12. Immunohistochemical staining in synovial tissues were performed. Expression of transcripts and proteins of inflammatory mediators were analyzed by semi-quantitative RT-PCR and immunoblotting. RESULTS: Recombinant protein consisted of 4th fas-1 domain truncated for H1 and H2 sequences and RGD peptide (MFK12), had M.W. of 10.4kDa. betaig-h3 mediated adhesion and migration of NIH3T3 cell line were significantly inhibited in a dose-dependent manner. Arthritis severity and incidence were efficiently reduced when CIA mice were treated with MFK12 at 30 mg/kg/day compared with the control. Immunohistochemical staining of joint tissues in MFK12 treated mice exhibited reduced angiogenesis. In treated mice, expression of transcripts regarding inflammatory mediators was markedly suppressed and immunoblotting of ICAM-1 and RANKL from whole extract of hind paws also showed a significant reduction. CONCLUSION: This study shows that MFK12 is effective in treating RA, although further study is warranted to improve the therapeutic efficacy.

Relationship between Physical Activity and Cognitive Function in the Elderly

BACKGROUND: Physical activity is considered an effective non-pharmaceutical preventive measure against cognitive impairment. This study was designed to investigate the correlation between physical activity and cognitive function. METHODS: Subjects were recruited from the Suwon Project, a cohort comprising a nonrandom convenience sample of ethnic Koreans aged 60 years or older. All participants completed study questionnaires which included questions about demographic characteristics, current and/or past medical history, and drug history. Cognitive functions were evaluated using the Korean version of Mini-Mental State Examination (K-MMSE), Korean version of Short Form Geriatric Depression Scale and Beck Anxiety Inventory. The total time spent to complete 10 physical activities was recorded on a daily basis. RESULTS: The total amount of time spent to execute 10 physical activities was 91.9+/-98.9 minutes per day. K-MMSE score was significantly associated with the duration of physical activity after adjustment for age, sex, educational level, depression, anxiety, and underlying diseases using multiple logistic regression analysis (beta=0.002, p<0.05). Categorizing physical activities into three groups by intensity yielded an interesting result; moderate intensity group demonstrated a direct correlation with cognitive function (beta=0.002, p<0.05). CONCLUSION: Although much remains to be elucidated, our results suggest that physical activity may be associated with cognitive function, after controlling for covariates.

Two cases of congenital carpal coalition with pain of the wrist / 대한내과학회지

Congenital carpal coalition is an uncommon anomaly that results from an incomplete joint cavitation of the primitive carpus. Congenital carpal coalition between the capitate and hamate is generally believed to be asymptomatic and, thus, is usually discovered on radiographs taken for unrelated reasons. We report two cases of congenital carpal coalition (capitate-hamate) associated with pain of the wrist.

beta ig-h3-Mediated Adhesion of Fibroblast-Like Synoviocytes in Rheumatoid Arthritis / 대한류마티스학회지

OBJECTIVE: beta ig-h3 is an extracellular matrix protein, which is overexpressed in synovial tissues of rheumatoid arthritis (RA) similar to adhesive glycoproteins. We sought to evaluate the compensatory role of beta ig-h3 with adhesive glycoproteins in mediating the adhesion of fibroblast- like synoviocytes (FLS) and to confirm the inhibitory effect of YH18 peptide of the 2nd fas-1 domain in beta ig-h3-mediated adhesion. METHODS: The adhesion of FLS isolated from synovial tissues of RA, was evaluated in 96 well microtiter plate coated with matrix proteins. Inhibitory effect of YH18 peptides from the 2nd and 4th fas-1 domains was estimated in beta ig-h3-mediated adhesion of FLS. RESULTS: The adhesion of FLS on beta ig-h3 was weaker than that of fibronectin and vitronectin. The beta ig-h3-mediated adhesion was enhanced by the stimulation with phorbol myristate acetate (PMA), but not by cytokines and growth factors. Combination of fibronectin with beta ig-h3 synergistically enhanced the adhesion of FLS, in contrast to the additive effect of vitronectin combined with beta ig-h3. YH18 peptide of the 2nd fas-1 domain did not block the beta ig-h3-mediated adhesion of FLS. CONCLUSION: Our results reveal that beta ig-h3 may regulate the adhesion of FLS through the interaction with adhesive glycoproteins and confirm that the essential motifs mediating adhesion on beta ig-h3 are different according to the type of cells.

Regulation of betaig-h3 Production in Rheumatoid Synovitis by Inflammatory Mediators / 대한류마티스학회지

OBJECTIVE: To investigate the expression pattern of transforming growth factor-beta-inducible gene-h3 (betaig-h3) within rheumatoid synovial tissue and the regulation of betaig-h3 synthesis in fibroblast-like synoviocyte (FLS). METHODS: Synovial tissues obtained from patients with rheumatoid arthritis and osteoarthritis were obtained during joint replacement surgery. betaig-h3 expression was evaluated with immunohistochemical stain. FLS was isolated from synovial tissues and stimulated with cytokines including TGF-beta, TNF-alpha, IL-1beta, IFN-gamma, IL-6, IL-4, and IL-10. betaig-h3 synthesis was measured using semiquantitative RT-PCR, ELISA, immunofluorescence stain, and flow cytometry. RESULTS: Expression of betaig-h3 was diffuse and abundant in both lining and sublining layers of rheumatoid synovium, which was more prominent than those of osteoarthritis. Production of betaig-h3 in FLS was regulated by TGF-beta1 in a dose-dependent manner and was highest at 5 ng/mL of TGF-beta1. TNF-alpha and IL-1beta upregulated the production of betaig-h3 from FLS synergistically with TGF-beta1 but other cytokines such as IL-4, IL-6, IL-10 did not affect. betaig-h3 synthesis was efficiently inhibited by dexamethasone at higher dose (100 nM) but not by cyclosporine-A. CONCLUSION: Production of betaig-h3, which is highly upregulated in rheumatoid synovitis, is differentially regulated by inflammatory cytokines.

MPO Gene Polymorphism in Behcet's Disease / 대한류마티스학회지

OBJECTIVE: Behcet's disease (BD) is a systemic vasculitis in which hyperfunction of neutrophils is one of the major pathophysiologic features. Myeloperoxidase (MPO) is an important neutrophilic lysosomal enzyme and has been implicated in tissue damage of BD. As the A allele of -463G/A polymorphism of the MPO gene is associated with diminished activity of MPO, we analyzed the association of -463G/A polymorphism of the MPO gene with BD. METHODS: We analyzed -463G/A polymorphism of the MPO gene in BD patients (n=101) and controls (n=138). Genotype of the MPO gene at position -463 was determined by PCR-RFLP assay using genomic DNA. RESULTS: The allele frequency of -463G/A polymorphism of the MPO gene did not deviate from the Hardy-Weinberg expectation in both BD patients and controls. There were no statistically significant differences in genotype distribution and allele frequency between patients and controls at position -463 (p=0.761 and p=0.549 respectively). Analysis of genotype distribution and allele frequency of the -463G/A according to sex did not show any difference between patients and controls. There were no statistically significant differences in clinical manifestations of BD among different genotypes. CONCLUSION: The present data indicate that the -463G/A polymorphism of the MPO gene was not associated with the susceptibility to and clinical manifestations of BD in Korea.

Hemorrhagic gastroenteritis with Henoch-Sch?nlein purpura in adult / 대한내과학회지

BACKGROUND: To evaluate clinical manifestations, endoscopic findings and response to treatment in adult Henoch-Sch?nlein purpura (HSP) patients with hemorrhagic gastroenteritis. METHODS: Twenty patients who were admitted to Kyungpook National University Hospital between 1996 and 2003 were included, based on the following criteria: 1) diagnosed as HSP according to the criteria proposed by Michel et al., 2) older than 15 years old and 3) had evidences of gastrointestinal (GI) bleeding. Thirteen HSP patients who were older than 15 years old and had no evidences of GI bleeding were recruited as controls. We evaluated the clinical features and findings of upper GI endoscopy and colonoscopy. RESULTS: Mean age and male to female ratio were not significantly different between patients with and without hemorrhagic gastroenteritis (age: 29.5 +/- 15.1 vs. 30.5 +/- 13.5; M:F=14:6 vs. 9:4, respectively). Patients with hemorrhagic gastroenteritis had a significantly higher frequency of petechiae on the upper extremities (p=0.015). In the multivariate analysis, petechial lesion on the upper extremities was a significant risk factor for hemorrhagic gastroenteritis (p=0.041). Mucosal lesions were found in 94.7% and 83.3% of patients on upper GI endoscopy and colonoscopy, showing that most patients (82.3%) had both upper and lower GI bleeding. Most patients with hemorrhagic gastroenteritis showed good response to high dose glucocorticoid therapy. Mortality and relapse rate were 10% and 5%, respectively. CONCLUSION: In adult HSP patients, presence of petechiae on upper extremities may be a risk factor for hemorrhagic gastroenteritis. The present data suggest that both upper and lower GI examinations are necessary for proper evaluation of HSP patients with hemorrhagic gastroenteritis.

VEGF Gene Polymorphisms In Ankylosing Spondylitis / 대한내과학회지

BACKGROUND: Angiogenesis may be important in the pathogenesis of ankylosing spondylitis (AS) and vascular endothelial growth factor (VEGF) has been known as one of the most potent pro-angiogenic factors. The association between single nucleotide polymorphisms (SNP) of the VEGF gene and AS has not been reported. We have sought to investigate the association of AS with candidate polymorphisms in the VEGF gene which have been reported to be associated with VEGF production. METHODS: We analyzed four SNPs of the VEGF gene in AS patients (n=146) and healthy controls (n=140). Allele frequencies of polymorphisms of the VEGF gene at positions -2578, -1154, -634 and 936 were determined by PCR-RFLP assay using genomic DNA. RESULTS: All four polymorphisms were not deviated from Hardy-Weinberg equilibrium in bothAS patients and controls. There were no statistically significant differences in genotype distributions and allele frequencies between patients and controls for the -2578C/A, -1154G/A, -634C/G and 936C/T. Analysis of genotype distributions of four SNPs according to sex did not show any difference between patients and controls. The frequency of HLA-B27 was similar between different genotypes in all four SNPs on the VEGF gene.The frequencies of haplotypes which were predicted using the Bayesian algorithm were not significantly different between patients and controls. CONCLUSION: The present data indicate that four selected SNPs of the VEGF gene are not associated with the susceptibility to AS in Korean patients.

Subclavian artery stenosis in neurofibromatosis type 1 / 대한내과학회지

Vascular involvement in neurofibromatosis type 1 (NF1) is a well known but clinically underestimated phenomenon. Arterial stenosis and aneurysm have been reported and among the stenotic vasculopathy, renal artery stenosis is the most common type. On PubMed search, there have been 9 reported cases of subclavian arterial involvement in NF1, of which only one case showed subclavian arterial stenosis. We report a 41-year-old man with NF1 and a subclavian artery stenosis who was treated successfully with percutaneous transluminal angioplasty.

A Case of Systemic Lupus Erythematosus Presenting with Protein Losing Enteropathy / 대한류마티스학회지

Protein losing enteropathy (PLE) is characterized by the loss of protein into the gastrointestinal tract that results in hypoalbuminemia and generalized edema. PLE is associated with several clinical disorders, but it is a rare manifestation of systemic lupus erythematosus (SLE), and it may be the presenting manifestation of SLE. We report a patient with SLE presenting with PLE, in whom methylprednisolone pulse therapy was highly effective. A 29-year-old women was admitted to our hospital with generalized edema. Laboratory findings revealed hypoalbuminemia, hypercholesterolemia and antinuclear antibody 1:160, speckled type. Mucosal biopsies of the duodenal bulb and terminal ileum revealed edema and dilated lymphatics with infiltration of chronic inflammatory cells. PLE was diagnosed by marked elevation of alpha-1 antitrypsin clearance in stool and abnormal radioactivity within small intestine on 99mTc-labeled human serum albumin scan. Hypoalbuminemia and generalized edema improved rapidly after methylprednisolone pulse therapy.

Prognostic Factors in Patients with Paraquat Poisoning and Effect of Hemoperfusion

PURPOSE: Paraquat is a nonselective contact herbicide that may induce damage to many organs poisoned with it. Due to the high mortality associated with paraquat poisoning, a prediction of the outcome is a prerequisite for determining the therapeutic modality. METHODS: To identify prognostic factors for paraquat poisoning, the authors analyzed retrospectively the clinical features and outcomes of 45 patients (mean age: 45.9 years; male-to-female ratio: 1.1 : 1) poisoned with paraquat herbicides; they had been admitted to the emergency room of Kyungpook National University Hospital between June 1992 and June 2001. RESULTS: Most patients (91.1%) ingested liquid paraquat concentrate; twenty-six (62%) patients had intended to commit suicide. The overall mortality rate was 64.4% (29 patients); the mortality rate with ingestion of more than two mouthfuls was 93.3%. Seventy-six percent of the fatal cases expired within 2 days after intoxication. Azotemia, hypokalemia, hypoalbuminemia, leukocytosis, and decreased level of arterial PaCO2 and bicarbonate on the first hospital day were significantly related with mortality. Increased level of serum AST on the 4th hospital day was an additional marker of mortality. The survival rates according to the Yamaguchi index were significantly different (A: 60%, B: 12.5%, C: 17%). There was no significant difference in the mortality rate between patients treated with and without hemoperfusion. CONCLUSION: Acid-base and electrolyte imbalances, an abnormal renal function, a low Yamaguchi index, and a positive urine paraquat test might be useful as early markers of poor prognosis. The effect of hemoperfusion remains to be determined by a further larger prospective study.

Decreased Serum NAD Glycohydrolase Activities in Liver Cirrhosis / 대한간학회지

BACKGROUND/AIMS: NAD glycohydrolase (NADase) is abundantly expressed in the liver. This expression is prominent in Kupffer cells. Since it was recognized that reticulendothelial function is impaired in liver cirrhosis, we assessed how these enzyme activities were altered in patients with liver cirrhosis. METHODS: Serum samples were obtained from 61 patients with liver cirrhosis (according to the criteria of Child-Pugh 15 were classified A, 24 were classified B, and 22 were classified C) and 16 healthy subjects. NADase activities were measured fluorometrically with [adenine-14C] NAD. The reaction mixture contained [adenine-14C] NAD and enzyme (patient serum). The reaction was stopped after a 30 to 480 min incubation by the addition of 50 L of 25% trichloroacetic acid. RESULTS: Serum NADase activities in 61 patients with liver cirrhosis were significantly lower than those in healthy subjects (33+/-14 vs. 55.6+/-13 p<0.001). Serum NADase activities in severe cirrhotic patients were significantly lower than those in mild to moderate cirrhotic patients (criteria of Child-Pugh, A: 40.6+/-6.4 vs. B: 38.6+/-13 vs. C: 21.8+/-14, p<0.001). NADase activities were correlated to prothrombin time (r = 0.69), and Apo A1 (r = 0.58) that were useful in identifying high-risk subjects for severe liver disease, but not asparate aminotransferase (AST) and alanine aminotransferase (ALT). Also, NADase activities reciprocally correlated with PGAA index (r = -0.78), Child-Pugh's score (r = -0.48), and serum alpha-2-macroglobulin (r = -0.72). CONCLUSIONS: NADase activities could be used as a single diagnostic marker for liver cirrhosis in addition to the Child-Pugh's score and PGAA index.

A Case of Tubular Adenocarcinoma on Fistula of Duodenal Bulb / 대한소화기내시경학회지

The first documented case of duodenal carcinoma was described by Hamburger in 1746. Primary adeno-carcinoma of duodenum is rare. Malignant tumors of the small bowel are reported to account for about 1% of all gastrointestinal carcinoma. The autopsy incidence of duodenal adenocarcinoma is about 0.3% of all malignancy. The second and third portions of the duodenum are the usual sites of adenocarcinoma. Cancer in the duodenal bulb is exceedingly rare. Most of them revealed an intraluminal mass or wall thickening. But we have experienced a case of exophytic growth pattern adenocarcinoma such as the fistula of duodenal bulb in 49 year old male patient with hematemesis. For its great rarity, we report this case with review of literatures.

A Case of Similar Pattern of Hepatotoxicity after Propylthiouracil and Methimazole / 대한간학회지

A 46-year-old male patient developed jaundice after 23 days' treatment of propylthiouracil (PTU) for Graves' disease. Serum alkaline phosphatase was elevated markedly with moderate increase in serum aminotransferase, and the peak level of total bilirubin was 7.3 mg/dL. After withdrawal of PTU, serum aminotransferase and bilirubin began to decrease simultaneously, and completely normalized. One week after the discharge from hospital, he received radioiodine treatment for Graves' disease, but he showed aggravation of hyperthyroidism and ophthalmopathy. So we prescribed methimazole inevitably 16 days' after the radiodiodine treatment. He developed jaundice again after 69 days' treatment of methimazole, but the pattern of hepatotoxicity was slightly different from that of the previous PTU-nduced hepatotoxicity. Serum aminotransferase increased slightly and quickly normalized after discontinuance of methimazole, but serum total bilirubin increased continuously and reached to 24.6 mg/dL. Eosinophilia was prominent and the result of liver biopsy was compatible with cholestatic jaundice. The patient was treated with prednisolone and recovered from jaundice rapidly.

A case of parenchymal consolidative lesions with air-bronchogram in chest CT scan / 결핵

No abstract available.