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Biomedical subjects

H Saari

Publications and source records attributed to H Saari.

47 records · Page 3Linked to original sources
PubMed1989

Non-proteolytic activation of latent human neutrophil collagenase and its role in matrix destruction in periodontal diseases.

Collagenases are known to be associated with tissue destruction in chronic inflammatory diseases such as periodontal diseases and rheumatoid arthritis. Collagenases are secreted by circulating inflammatory cells (polymorphonuclear leukocytes and monocytes), resident mesenchymal cells and epithelial cells in latent forms, which can be activated by proteases and compounds reacting with protein thiol groups. We have studied here the effects of oxygen-derived free radicals (ODFR) on latent human neutrophil collagenase. Also, in order to elucidate the cellular sources of collagenases, the ability of human gingival crevicular fluid (GCF) collagenases both from adult periodontitis (AP) and localized juvenile periodontitis (LJP) patients to degrade soluble interstitial collagen types I and II was studied. ODFR generated by the xanthine oxidase/hypoxanthine system in the presence of trace amounts of iron and EDTA activated latent neutrophil collagenase to an equal extent as the known activators phenylmercuric chloride and gold thioglucose. ODFR activation was inhibited by desferoxamine and mannitol as well as by superoxide dismutase and catalase. Clear differences in the susceptibility of collagen types I and II to AP and LJP GCF collagenases were observed. AP GCF collagenase degraded type I and II collagens at equal rates, resembling the substrate-specificity of human neutrophil collagenase. LJP GCF collagenase degraded type I collagen considerably faster than type II collagen, which was only negligibly degraded. This corresponds to the substrate specificity of fibroblast collagenase. Zymographic evaluation of gelatinolytic proteases showed the presence of 90 and 68 kD gelatinases in both AP and LJP GCF. Non-proteolytic means apparently provide a potent activation pathway of neutrophil collagenase in vivo and the hydroxyl radical was identified to be one of the potent activating oxidants.(ABSTRACT TRUNCATED AT 250 WORDS)

Body Fluids↗
PubMed1989

Concentration and degree of polymerization of hyaluronate in equine synovial fluid.

In addition to its well-known physicochemical properties, hyaluronate (HA) has recently been shown to have important biological and pathophysiologic regulatory effects on granulocytes, monocytes, fibroblasts, and endothelial cells, as well as on the healing of wounds and various joint disorders. Many of these effects depend on or are reflected in the concentration and degree of polymerization of HA. Therefore, high-performance liquid chromatography with size-exclusion column was used to characterize the concentration and degree of polymerization of HA in equine synovial fluid (SF). The mean (+/- SD) HA concentration was 0.47 +/- 0.19 mg/ml and there was no difference between control joints and those with positive response to local anesthetic administration (0.61 +/- 0.20 mg/ml vs 0.42 +/- 0.17 mg/ml), suggesting that in horses with acute traumatic synovitis causing lameness, HA concentration in SF cannot be used as a marker for the condition. High-performance liquid chromatograms disclosed considerable variation between horses in the degree of polymerization reflected in the peak area to height ratio (mean +/- SD, 3.207 +/- 0.447; range, 2.229 to 3.915), indicating differences in local synthesis, degradation, or mobilization into lymph of SF HA. In addition, the correlation between SF HA concentration and degree of polymerization was 0.760 (P less than 0.01; linear regression analysis), suggesting that HA concentration and chain length are independently regulated.

Animals↗
PubMed1989

Cellular and molecular aspects of inflammation.

Cellular host reaction to noxious agents and damaging events consists of inflammatory, immune and repair responses. These are usually involved in different phases of the host reaction in a well co-ordinated manner, contributing to the well-being of the host. However, when they are excessive, uncontrolled or occur in a vulnerable anatomic location, they can contribute greatly to injury. In general, the effects of the initiating stimulus are much enhanced by secondary involvement of amplification loops, leading to recruitment of nonspecific cells. The number of initially stimulated and/or actively involved cell is, therefore, usually low but of crucial importance for the outcome of the process. As important as understanding of the mechanisms responsible for initiation and amplification of the host response is knowledge of the negative feedback loops responsible for down-regulation of the whole process.

Cell Line↗
PubMed1988

An immunoperoxidase-autoradiography double labeling method for analysis of lymphocyte activation markers and DNA synthesis.

An immunoperoxidase-autoradiography double labeling method for analysis of lymphocyte activation markers and DNA synthesis is described. For this study expression of MHC locus II coded Ia antigen, interleukin-2 receptor, transferrin receptor and gp 40/80 glycoprotein was analyzed using monoclonal antibodies in avidin-biotin-peroxidase complex staining combined with visualization of [3H]thymidine incorporation by autoradiography. Compared to spontaneous [3H]thymidine incorporation assay information is obtained at single cell level. In contrast to blast indexes calculated from MGG stained preparates, information on the expression of various functional cell surface structures as well as DNA synthesis is also obtained. Double-assay for lymphocyte phenotype and DNA synthesis by flow cytometry might be preferred to light microscopy, but the widespread use of immunoperoxidase staining and autoradiography may make this new kind of approach more easily available. Other advantages worth considering are the possibility of transporting, staining and counterstaining as microscope slides and the permanent nature of the documentation and morphological information obtained. In our experience, this method seems to be useful for studying resting peripheral blood lymphocytes as well as mitogen and antigen induced changes in the lymphocyte activation state.

Antibodies, Monoclonal↗
PubMed1988

Synovial fibroblasts.

Chronic synovitis refers to fibrin deposits on the surface of proliferating superficial synovial lining cells leading to villous hyperthrophy, and associated with foci of cell necrosis and infiltration of chronic inflammatory cells. The superficial synovial lining cells include fibroblast-like type B cells and macrophage-like type A cells. Fibroblast- and macrophage-like cells in the early or leading edge of pannus may represent an extension of these cells, which themselves may be nothing else than stromal fibroblasts and macrophages adapted to the particular micro-milieu prevailing at the interface of hyaluronate (HA) containing synovial fluid and richly vascularized loose connective tissue in the sublining stroma. In all three locations fibroblasts are exposed to various humoral substances, extracellular matrix (ECM) and cell-cell contacts, which may modify their phenotype and function. Therefore, one would expect differences in the fibroblasts in inflammatory and non-inflammatory synovial tissue. These changes can be best understood by considering some of the basic fibroblast properties, namely migration, substrate adherence, proliferation and synthesis and degradation of ECM.

Animals↗
PubMed1980

Interactions of Ca2+ and H+ with heme A in cytochrome oxidase.

Ca2+ ions shift the absorption spectrum of reduced cytochrome a in mitochondria by acting from the outside of the membrane. In isolated cytochrome oxidase the shift may be induced by either Ca2+ or H+, the apparent pK varying between 6.20 and 5.75 depending on the state of cytochrome a3. Studies of the Soret band show that Ca2+ also shifts the spectrum of ferrocytochrome a3 in isolated oxidase in contrast to the situation in mitochondria or isolated oxidase reconstituted into liposomes. Model studies with reduced bis-imidazole heme A reveals an analogous spectral shift induced by Ca2+. Esterification of the propionate carboxyls of heme A abolishes the spectral shift, suggesting that it is due to interaction of Ca2+ with these groups. When taken together with the data with intact mitochondria, this suggests that the propionate side chains of cytochrome a are accessible to Ca2+ and H+ from the outside of the mitochondrial membrane. In the soluble enzyme both hemes a and a3 are accessible. Thus heme a may be located near the outside of the inner membrane whereas heme a3 experiences a different environment in which no Ca2+ shift occurs.

Animals↗
PubMed1975

A spectral shift in cytochrome a induced by calcium ions.

Ca2+ induces a red shift in the absorption spectrum of ferrocytochrome a when added to uncoupled mitochondria, sub-mitochondrial particles or isolated cytochrome aa3. The shift is identical within experimental error to the previously reported energy-linked shift in intact mitochondria (Wikström, M. K. F. (1972), Biochim. Biophys. Acta 283, 385-390). One mol of calcium produces the shift in one mole of cytochrome a, the KD being approx. 20-30 muM. The calcium-induced shift is readily reversed by chelating agents such as EDTA, ethyleneglycol-bis-(beta-aminoethyl ether)N,N'-tetraacetic acid (EGTA) and ATP and is insensitive to uncoupling agents and inhibitors of calcium transport (La3+ and ruthenium red). It is shown that the binding site for calcium that is responsible for the spectral shift is located on the outside of the permeability barrier of the mitochondrial cristae membrane. It is proposed that calcium simulates the energy-linked shift in cytochrome a by binding to a site of cytochrome aa3 that is occupied by protons in energized mitochondria and that is located at the external surface of the mitochondrial membrane.

Adenosine Triphosphate↗
PubMedDate not supplied

Ochronosis: a report of a case and a review of literature.

A patient with alkaptonuria and ochronotic pigment deposited in articular cartilage and sclerae clinically manifested a serious osteoarthritis of the peripheral and axial joints and synchondrosis, typically involved in long lasting cases of this hereditary defect of homogentisic acid oxidase. This is the first patient with this disorder reported, where a non-cemented total knee prosthesis (PCAR) was applied on both knees. This was possible due to the good quality of the bone stock, which did not seem to be impaired by ochronosis. Our patient had no cardiac symptoms or murmurs, but had a slight calcification in the annulus of aorta observed with echocardiography, a useful new method for screening this disease manifestation. A third new aspect reported is the immunopathology of the synovial tissue. Small pieces of torn-off cartilage were seen embedded in the synovial stroma. This was associated with a slight hyperplasia of the C3bi-receptor positive and proline hydroxylase positive type A and B synovial lining cells. Perivenular infiltrates contained CD2 positive T lymphocytes, mostly belonging to the CD4 subset, and some C3bi-receptor positive monocytes. Activated CD25 positive and immunoglobulin light chain positive T and B lymphocytes were absent or few. Because modern medicine has much to offer to those suffering from this ancient inborn error of metabolism in the form of new specific diagnostic methods and new surgical modes of treatment, such as endoprosthesis surgery and cardiac valve replacement, we also present a literature overview of this interesting condition.

Dioxygenases↗