Prostanoids, which consist of the prostaglandins (PGs) and the thromboxanes (TXs), exert a variety of actions in the body, which are mediated via specific cell surface receptors. They consist of five types of receptors named the TP, IP, EP, FP and DP receptors. The EP receptor have four subtypes, the EP₁, EP₂, EP₃ and EP₄ receptors. However, none of the receptors had been isolated and cloned until the TXA₂ receptor was purified from human blood platelets and its cDNA cloned. By homology screening in mouse cDNA libraries, the structures of all of the mouse prostanoid receptors have been identified.
These studies have clearly shown that all of the prostanoid receptors belong to the G-protein-coupled, rhodopsin-type receptor superfamily, and that they constitute a new subfamily of receptors. On the other hand, their ligand binding characteristics and signal transduction were studied using the expresson system of the cloned receptors. These studies have clarified the structure and function of the prostanoid receptors.

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Myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA) has been widely detected in some diseases. It appears that the titer of MPO-ANCA is not always correlated with the activity of the disease. The epitope mapping of MPO-ANCA using recombinant proteins has been demonstrated to be effective in elucidating their etiology. The recombinant fragments of the MPO molecule have been expressed in E. coli without the association of the sugar moiety for the epitope analysis. The Western blotting and ELISA using the purified recombinant deletion mutants of human MPO has been established. It seems to be useful for sub-classifica-tion of MPO-ANCA related vasculitis. When epitope of sera of patients with MPO-ANCA-related renal diseases and vasculitis was analyzed by the Western blotting. Most of the sera reacted with either of the region of N- or C-terminus of the heavy chain, whereas no serum reacted with the light chain regions. Recently, some model mice of MPO-ANCA have been examined also.

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Here we summarize our biochemical and histochemical characterization of L-selectin ligands in the kidney. The staining pattern with anti-sialyl Le^X antibodies (KM-93, FH-6 and CSLEX-1) was distinct from that with L-selectin-IgG chimera (LEC-IgG), suggesting that sialyl Le^X antigen is not associated with ligands for L-selectin in the kidney, unlike other glycoprotein ligands for L-selectin. Immuno-precipitation analysis with LEC-IgG revealed that a proteoglycan-like molecule from a renal tubule-derived cell line specifically bound to L-selectin. Using sequential column chromatography, we isolated this proteoglycan-like molecule and identified it as versican, a large chondroitin sulfate proteoglycan. Histochemical examination confirmed that versican is localized in the distal straight tubules of the rat kidney where L-selectin ligands are detected. Interestingly, after ureteral obstruction in the rat, versican disappeared from the renal tubules and appeared in the vascular bundles. Concomitantly, a massive leukocyte infiltration was observed around the vascular bundles, which was significantly inhibited with administration of an anti -L-selectin monoclonal antibody. These results suggest that versican secluded in the renal tubules under physiological conditions may play a role in leukocyte infiltration as an L-selectin ligand by changing its localization under pathological conditions.

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The use of immunoglobulin for human in vivo treatment has been limited to a great extent by the patient's immune response to non human antibodies in immunotherapy. Since it is hard to accepted the idea in public society that periodontal diseases cause death in humans, the development of safe antibodies in passive immunization is required. Several methods have been developed for the production of safe antibodies such as recombinant single chain Fv (ScFv) and human type antibodies. Porphyromonas gingivalis, a Gram-negative anaerobe, appears to be one of the most virulent microorganisms in relation to adult periodontitis. Coaggregation and hemagglutinin factors are important virulent factors in colonization on host tissues. This paper briefly introduces here the methods for preparation of safe immunoglobulins and summarizes our own attempts in preparations of ScFv and human type antibodies which are capable to inhibit the activities of coaggregation and hemagglutinin of P. gingivalis.

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We evaluated the role of interleukin-8 (IL-8) in patients with various acute and chronic inflammatory lung diseases and sepsis with multiple organ dysfunction syndrome. Initially, in patients with acute lung injury, such as acute respiratory distress syndrome (ARDS) and inhalation injury, IL-8 levels in bronchoalveolar lavage fluid (BALF) were significantly elevated. With regard to latter patients, the BALF IL-8 levels well correlated with the degree of successive respiratory dysfunction. Secondly, among patients with chronic inflammatory lung diseases, BALF IL-8 levels were significantly elevated in patients with acutely exacerbating idiopathic pulmonary fibrosis (IPF), hypersensitivity pneumonitis and chronic lower respiratory tract infection. Furthermore, in IPF patients, alveolar macrophages produced significantly larger volume of IL-8 in response to endotoxin, which may be one of the key mechanisms of acute exacerbation in IPF. Finally, in septic patients, the higher serum IL-8 levels were associated with the complication of DIC, renal failure and central nervous system dysfunction, indicating the possible involvement of IL-8 in these conditions.
These results strongly support our hypothesis that IL-8 plays a prominent role in above diseases or conditions and thus could become a good target for anti-mediator therapy.

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We created synovial enhancement score (SES) of the wrist with Gd-DTPA enhanced MRI for patients with rheumatoid arthritis (RA) . To evaluate the clinical predictive values, various clinical parameters including age, duration of disease, erythrocyte sedimentation rate (ESR), Lansbury activity index (LI) were retrospectively surveyed. A total of 149 MRI examinations from 96 rheumatoid patients were reviewed and correlated with matched clinical data, out of which ESR and LI showed relatively high correlation coefficients (0.43 with the p-value of<0.001 and 0.44 with the p-value of 0.006, respectively) . To determine whether patients with seronegative RA differ in SES from patients with seropositive RA, 25 patients with seronegative RA were closely matched with seropositive control subjects. In spite of radiographic carpal predominancy previously reported in seronegative rheumatoid patients, seronegative RA patients had significantly lower SES (11.9 vs 19.1 points with p-value of 0.0006) . MRI synovial enhancement score of the wrist with Gd-DTPA sppears to have a good clinical predictive value for RA patients. Seronegative RA patients had less severe synovial enhancement of the wrist as compared with seropositive RA patients.

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Objects: To assess the effects of Argatroban which was developed as an antithrombin agent, we experimentally investigated the number of inflammatory cells and astrocytes infiltrated and/or appeared in injured lesion of rat brain.
Methods: Gelatins soaked with Argatroban or saline were placed in the artificial cavities of brain defect for assessing the grade of infiltrating inflammatory cells using ordinary hematoxylin-eosin (HE) and immunohistochemical (IHC) stains. Polymorphonuclear leukocytes by HE stain and monocyte/macrophage positive cells, glial fibrillary acidic protein (GFAP) positive and vimentin positive astrocytes by IHC stain were compared between Argatroban and saline (control) treated group.
Results: Argatroban suppressed accumulation of inflammatory cells, both polymorphonuclear leukocytes and monocyte/macrophage positive cells, and vimentin positive astrocytes along the brain defect edge, but had no effect on GFAP positive astrocytes along the brain defect edge.
Conclusion: Argatroban may minimize the secondary brain damage through suppressing the infiltration of inflammatory cells and excessive gliosis comprised of vimentin positive astrocytes and have good effects on the neural regenaration.

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