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Biomedical subjects

Hajime Sugiyama

Publications and source records attributed to Hajime Sugiyama.

6 recordsLinked to original sources

TGF-beta type I receptor kinase inhibitor down-regulates rheumatoid synoviocytes and prevents the arthritis induced by type II collagen antibody.

Rheumatoid arthritis (RA) is characterized by hypertrophic synovial tissues comprising excessively proliferating synovial fibroblasts and infiltrating inflammatory cells. Transforming growth factor-beta (TGF-beta) is a multifunctional cytokine that regulates cell growth, inflammation and angiogenesis by acting on various cell types. In RA synovial tissues, TGF-beta is expressed at high levels. However, the precise role of TGF-beta in RA remains unclear. We herein demonstrated a causal link between the TGF-beta-induced RA synovial cell proliferation and induction of platelet-derived growth factor (PDGF)-AA. In addition, TGF-beta induced IL-6 and vascular endothelial growth factor (VEGF) production by RA synovial fibroblasts associated with nuclear factor-kappa B activation. These effects of TGF-beta on RA synovial fibroblasts were suppressed by TGF-beta type I receptor kinase inhibitor HTS466284. Furthermore, HTS466284 significantly prevented anti-collagen type II antibody-induced arthritis in mice according to the clinical manifestations, histology, tumor necrosis factor-alpha, PDGF and VEGF expression and 5-bromo-2'-deoxyuridine incorporation. These in vitro and in vivo results suggest that TGF-beta plays a role in the development of synovial hyperplasia consisting of synovial cell proliferation, inflammation and angiogenesis. The blockade of TGF-beta signaling may thus become an additional strategy for the treatment of RA.

Animals↗

Pseudogout attack induced during etidronate disodium therapy.

We report the first case of pseudogout attack in the distal interphalangeal (DIP) joints during etidronate disodium therapy. A 64-year-old woman had intermittent administration of etidronate disodium (Didronel; Sumitomo, Osaka, Japan) alone because of osteoporosis. Each cycle consisted of a daily dose of 200 mg for 2 weeks, repeating every 12 weeks. Two weeks after completing the third cycle, severe pain and swelling occurred in the DIP joints of the right middle, ring, and left ring finger; and skin ulcer formation was observed on the dorsal side of the DIP joints of the right middle and ring fingers as well as the left ring finger. Because monoclinic calcium pyrophosphate crystals were detected in the synovial fluid from the DIP joints of the right middle finger, we diagnosed these symptoms as induced by pseudogout attack. Oral loxoprofen sodium at a daily dose of 180 mg resulted in rapid symptom resolution. A decrease in function of calcium metabolism in elderly persons has been reported to be a cause of pseudogout attack. On the other hand, distal interphalangeal joint arthritis presenting as Heberden's nodes is a common condition in elderly patients. Therefore, pseudogout attack should be considered as an adverse drug reaction when administering bisphosphonate in elderly patients with Heberden's nodes.

Anti-Inflammatory Agents, Non-Steroidal↗

Hydroxyapatite-coated total knee arthroplasty in rheumatoid arthritis patients: a short-term follow-up study.

OBJECTIVE: To determine the outcome of cementless hydroxyapatite-coated total knee prosthesis in rheumatoid patients. DESIGN: Analytical. PLACE AND DURATION OF STUDY: University of Yamanashi Hospital, Japan, from October 1999 to September 2002. PATIENTS AND METHODS: Twenty total knee arthroplasties using HA-coated Scorpio Superflex CR and Delta 7000 series were performed in 17 rheumatoid patients. Pre and postoperative results were compared using JOA scores. RESULTS: Male: female ratio was 16:1, average age was 67 years and mean duration of follow-up was two years. JOA scores improved significantly (p<0.05) postoperatively from an average of 37 to 80. Varus and valgus angular deformities improved significantly and 90% of the knees had alignment between zero and 5 degrees of valgus angulation with an average tibiofemoral angle (FTA) of 172. The radiographic findings revealed no radiolucent lines at two years follow-up. Distal femur osteolysis was not observed. CONCLUSION: The clinical results were excellent at 2-year follow-up, which are in agreement with other reports using hydroxyapatite-coated knee prosthesis.

Aged↗

Computational evaluation of the specific interaction between cation and mismatch base pair.

Ab initio calculations were carried out to characterize the structure and energetic of silver cation (Ag (I)) complex with cytosine (C:Ag:C) and mercury cation (Hg (II)) complex with thymine (T:Hg:T) systems. These metal-modified mismatch base pairs have been optimized using Hatree-Fock method without any symmetry constrains. Using above methods, the models of Ag (I) in a crosslink between O2 carbonyl oxygen of cytosine, O2(C):Ag:O2(C), and Hg (II) in a crosslink between N3 nitrogen atom of thymine, N3(T):Hg:N3(T) were obtained. Furthermore, the interaction energies of C:Ag:C and T:Hg:T models were estimated. The result showed that the coordination silver (I) cation with cytosine is more stable than hydrate state.

Base Pair Mismatch↗

Hematopoietic activity of common marmoset CD34 cells isolated by a novel monoclonal antibody MA24.

OBJECTIVE: We focused on a small New World monkey, the common marmoset (Callithrix jacchus), to establish a nonhuman primate model of the treatment of hematological disorders. In this study, we developed the first monoclonal antibodies (MAbs) against marmoset CD34 and tested the in vitro and in vivo hemopoietic activity of cell populations isolated using one of these MAbs. METHODS AND RESULTS: Marmoset cDNA encoding a human CD34 homologue was cloned from bone marrow (BM)-derived RNA using reverse transcription polymerase chain reaction and rapid amplification of cDNA ends. The amino acid sequence of the marmoset CD34 had 81% homology with the human sequence. Five mouse MAbs were raised against marmoset CD34 transfectant. One representative MAb, MA24 (IgM), reacted with approximately 0.5 to 1% of BM mononuclear cells (MNCs), where the colony-forming unit granulocyte/macrophage (CFU-GM) was enriched approximately 11- to 75-fold as compared with the whole BM MNCs. Multilineage differentiation of marmoset CD34+ cells in NOD/SCID mice was confirmed by flow cytometry 1 month after xenotransplantation. CONCLUSION: These results demonstrated that MA24 is useful for the analysis and enrichment of hematopoietic progenitor cells in the marmoset model for preclinical experiments.

Amino Acid Sequence↗

Destructive pulmonary embolism in a patient with community-acquired staphylococcal bacteremia.

We report a 17-year-old man with destructive pulmonary embolism caused by Staphylococcus aureus bacteremia. The patient was not immunocompromised and had neither underlying diseases nor risk factors, such as concomitant influenza viral infection, which exacerbate staphylococcal infections. The rapid and extensive progression of pulmonary involvement in all lung fields make this a rare case; there have been few reports in the literature describing a similar radiographic appearance in patients with community-acquired staphylococcal bacteremia. In-vitro studies did not demonstrate the production of enterotoxins or toxic shock syndrome toxin 1 (TSST-1) by the isolated strain, but genetic analysis detected Panton-Valentine leukocidine gene from the strain. Subsequent empyema with bilateral pneumothorax was prolonged because of superinfection with both methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa. Optional surgical treatments, including thoracostomy and thoracopneumoplasty, finally improved his condition.

Adolescent↗