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J Korean Med Sci. 2000 Oct;15(5):485-93.
Expression of osteopontin in calcified coronary atherosclerotic plaques.

Kwon HM, Hong BK, Kang TS, Kwon K, Kim HK, Jang Y, Choi D, Park HY, Kang SM, Cho SY, Kim HS.

Yonsei Cardiovascular Center and Research Institute, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea. kwonhumc.yonsei.ac.kr

Advanced atherosclerosis is often associated with dystrophic calcification and remodeling of extracellular matrix of vascular wall. Recently many studies have documented a general relationship between calcification and severity of coronary disease, and discussed the feasibility of electron beam computed tomography for detecting and quantifying the coronary artery calcification in the patients. The present study investigated the expression and the localization of osteopontin, one of noncollagenous bone matrix protein, within the calcified coronary arteries. Autopsy-derived coronary artery specimens were scanned and reconstructed to visualize the pattern of coronary calcification using a novel microscopic computed tomography technique. The localization of the osteopontin were evaluated by immunohistochemial stain with LF7. The present study showed that the pattern of coronary calcification is variable and the expression of osteopontin is localized mainly to calcified lesion. The smooth muscle cells in addition to macrophage expressed osteopontin protein in human coronary atherosclerotic plaques. Soluble osteopontin released near to the sites of vascular calcification may represent an adaptive mechanism aimed at regulating the process of vascular calcification.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11068982&dopt=Abstract

Eur J Immunol. 2000 Oct;30(10):2815-23.
Contribution of OX40/OX40 ligand interaction to the pathogenesis of rheumatoid arthritis.

Yoshioka T, Nakajima A, Akiba H, Ishiwata T, Asano G, Yoshino S, Yagita H, Okumura K.

Department of Joint Disease and Rheumatism, Nippon Medical School, Tokyo, Japan.

OX40 ligand (OX40L) and OX40 (CD134) are a pair of cell surface molecules belonging to the TNF/TNF receptor family. Interaction of OX40L with its receptor OX40 is thought to be important in T cell activation through T cell/antigen-presenting cell interaction. However, involvement of these molecules in the pathogenesis of rheumatoid arthritis (RA) remains unclear. To explore the contribution of OX40/OX40L interaction to the pathogenesis of RA in vivo, we evaluated the effect of a neutralizing anti-OX40L monoclonal antibody (mAb) on the development of collagen-induced arthritis (CIA) in DBA/1 mice as an animal model for RA. Administration of anti-OX40L mAb into type II collagen (CII) -immunized DBA/1 mice dramatically ameliorated the disease severity. In vivo treatment with anti-OX40L mAb did not inhibit the expansion of CII-reactive T cells, but suppressed IFN-gamma and anti-CII IgG2a production. Therefore, OX40/OX40L interaction appears to play a critical role in the development of CIA by enhancing Th1-type autoimmune response. In addition, T lymphocytes in synovial fluid and synovial tissue from RA patients expressed OX40, while OX40L was expressed on sublining cells in synovial tissue. These results indicate that OX40/OX40L interaction may play a critical role in the development of RA.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11069062&dopt=Abstract

Am J Respir Crit Care Med. 2000 Nov;162(5):1949-56.
Characteristic elevation of matrix metalloproteinase activity in idiopathic interstitial pneumonias.

Suga M, Iyonaga K, Okamoto T, Gushima Y, Miyakawa H, Akaike T, Ando M.

First Department of Internal Medicine and Department of Microbiology, Kumamoto University School of Medicine, Kumamoto, Japan.

Destruction of subepithelial basement membrane is a key event in the pathogenesis of idiopathic pulmonary fibrosis (IPF). To evaluate the role of matrix metalloproteinases (MMPs) in parenchymal remodeling in idiopathic interstitial pneumonia (IIP), we studied MMP-2 and -9 activity, in bronchoalveolar lavage fluid (BALF) by zymography and the expression of MMP-2 and -9 and TIMP-2 in lung tissue by immunohistochemistry. BALF and lung tissues were collected from 26 patients with usual interstitial pneumonia (IPF-UIP), 11 with nonspecific interstitial pneumonia (NSIP), and 6 with bronchiolitis obliterans organizing pneumonia (BOOP). IPF-UIP cases showed predominant expression of MMP-9, whereas NSIP and BOOP cases showed predominant MMP-2 expression in BALF and in tissues. In BALF samples from rapidly progressive IPF-UIP cases, neutrophil-derived MMP-9 activity, as well as MMP-9 active form were characteristically detected. Furthermore, the MMP-9 activity correlated significantly with an increase of neutrophils in BALF, whereas the MMP-2 activity associated with NSIP and BOOP correlated with an increase of lymphocytes. These results indicate that MMP-9 in IPF-UIP and MMP-2 in NSIP and BOOP may contribute to pulmonary structural remodeling through type IV collagenolytic activity. The characteristic contributions of matrix-degrading proteins may relate to the distinct prognostic features of these diseases.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11069839&dopt=Abstract

Scand J Gastroenterol. 2000 Sep;35(9):969-75.
Experimental model of hepatic fibrosis following repeated periportal necrosis induced by allylalcohol.

Jung SA, Chung YH, Park NH, Lee SS, Kim JA, Yang SH, Song IH, Lee YS, Suh DJ, Moon IH.

Dept. of Internal Medicine, Asan Medical Center, Ewha Womans University College of Medicine, Seoul, Korea.

BACKGROUND/AIMS: In most patients with chronic viral hepatitis the predominant lobular location of hepatic necrosis and fibrosis is the periportal zone. We established a new simple model of hepatic fibrosis in rats by repetitive periportal necrosis with allylalcohol. METHODS: Of 40 male adult rats, 30 were injected with 0.62 mmol/kg of allylalcohol intraperitoneally twice a week, the remaining 10 with normal saline as controls. Ten rats were killed at each of 4, 8, and 16 weeks later. The extent of fibrosis was evaluated according to the portal-portal extent. Transforming growth factor (TGF) beta1 mRNA in liver tissues was detected by reverse transcriptase polymerase chain reaction, and its levels were determined by the endpoint titers of serial two-fold dilutions of cDNA. RESULTS: After 4 weeks, periportal fibrosis was produced in only 6 out of 10 rats, and was mild in extent. However, after 8 weeks, 8 out of 9 survivors showed moderate to severe fibrosis, which corresponded to a score of 7 or more. The extent of fibrosis correlated significantly with the amount of collagen and TGFbeta1 mRNA expression in liver tissues. The collagen content and expression of TGFbeta1 mRNA were also upregulated significantly in liver tissues with a fibrosis score of 7 or more. CONCLUSIONS: Hepatic fibrosis can be sufficiently induced by repetitive intraperitoneal injection of 0.62 mmol/kg of allylalcohol twice a week for 8 weeks. This simple model of hepatic fibrosis, in which TGFbeta1 is overexpressed at the transcriptional level, may be useful in the study of patients who have predominantly periportal necrosis and fibrosis.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11063159&dopt=Abstract

Croat Med J. 2000 Dec;41(4):396-400.
Determinants of reduced bone mineral density and increased bone turnover after kidney transplantation: cross-sectional study.

Kusec V, Smalcelj R, Cvijetic S, Rozman B, Skreb F.

Clinical Institute of Laboratory Diagnosis, Zagreb University Hospital Center, Kispaticeva 12, 10 000 Zagreb, Croatia. rkuseudjer.irb.hr

AIM: To analyze bone metabolism and the risk factors of bone loss in kidney transplant recipients. METHODS: The bone mineral density (BMD) of the lumbar spine, femoral neck, and radius was determined by dual-energy X-ray absorptiometry in 52 patients 8 days to 228 months after kidney transplantation. Total and bone alkaline phosphatase (BAP), osteocalcin, procollagen, type I collagen telopeptide, collagen cross links, calcium, intact parathyroid hormone (iPTH), and creatinine were measured in all patients. RESULTS: The BMD of the spine and femoral neck was reduced in 57%, and of the radius in 72% of the patients. Reduced BMD was associated with significantly increased levels of iPTH, osteocalcin, and procollagen. Dialysis duration negatively correlated with the radius BMD in all patients and the femoral neck BMD in women. No relationship between BMD and length of post-transplantation time, age, cumulative steroid dose, or serum creatinine level was established. All biochemical parameters negatively correlated with the spine BMD, but not with the BMD of the femoral neck and radius. The correlation between BAP and telopeptide and length of post-transplantation time was also negative. No difference in the incidence of osteopenia was found between genders. CONCLUSION: Osteopenia/osteoporosis and increased bone turnover were present in more than a half of the kidney transplant recipients. Reduced BMD was associated with enhanced bone remodeling, primarily mediated by PTH hypersecretion. The length of post-transplantation period, cumulative steroid dose, gender, and age could not be identified as risk factors of reduced BMD.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11063762&dopt=Abstract

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