Search PubMed⌕ Search

Biomedical subjects

K Torikai

Publications and source records attributed to K Torikai.

At least 37 records · Page 2Linked to original sources
PubMed1999

Alteration of the cellular response to interleukin-1 beta by SV40 large T antigen in rheumatoid synovial fibroblasts.

The large T antigen of SV40 (LT) has been widely used to immortalize primary cells for various studies. In this study, synovial fibroblasts of a patient from rheumatoid arthritis (RA) were transformed with LT gene to analyze the effect of SV40-mediated transformation on the production of cytokines, such as IL-6, IL-8, and GM-CSF, that are under the control of interleukin-1 beta (IL-1 beta), a physiological inducer of nuclear factor kappa B (NF-kappa B). It was noted that the basal levels of GM-CSF and IL-8 were upregulated, whereas that of IL-6 was downregulated. Moreover, the extents of induction of these cytokines in response to IL-1 beta were markedly downregulated in synovial fibroblasts transformed by LT as compared from parental cells. Although IL-1 beta could translocate NF-kappa B to the nucleus in all cells, some of the transformed cells exhibited nuclear translocation of NF-kappa B even before the stimulation with IL-1 beta, suggesting that transformation of LT resulted in the constitutive activation of NF-kappa B, either directly or indirectly. In order to examine whether LT downregulate the kappa B-dependent gene expression, we performed the transient luciferase gene expression assay. We found that cotransfection of LT did not downregulate the kappa B-dependent gene expression that was stimulated with L-1 beta. These observations suggest that the apparent inhibitory effect of LT on the IL-1-induced expression of cytokines may not be through its direct action on the NF-kappa B transactivation.

Antigens, Polyomavirus Transforming↗
PubMed1998

Suppression of tumor promoter-induced oxidative stress and inflammatory responses in mouse skin by a superoxide generation inhibitor 1'-acetoxychavicol acetate.

Double applications of phorbol esters trigger excessive reactive oxygen species (ROS) production in mouse skin. Previously reported data suggest that the two applications induce distinguishable biochemical events, namely, priming and activation. The former is characterized as a recruitment of inflammatory cells, such as neutrophils, by chemotactic factors to inflammatory regions and edema formation. The latter is responsible for ROS generation. Thus, inhibitory effects of 1'-acetoxychavicol acetate (ACA), previously reported to be a superoxide generation inhibitor in vitro, on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced oxidative stress and inflammatory responses in mouse skin model were examined using a double application of ACA. We demonstrated that two pretreatments and pretreatment with ACA (810 nmol) in the activation phase suppressed double TPA application-induced H2O2 formation in mouse skin. ACA exhibited no inhibitory effects on edema formation and the enhancement of myeloperoxidase activity during the first TPA treatment, whereas the anti-inflammatory agent genistein administered at the same dose inhibited both biomarkers. No inhibitory potential of ACA for TPA-induced H2O2 formation in the priming phase was confirmed. On the other hand, in the in vitro study, ACA inhibited ROS generation in differentiated HL-60 cells more strongly than did 1'-hydroxychavicol, which showed no inhibition by pretreatment in the activation phase. In addition, allopurinol did not inhibit double TPA application-induced H2O2 formation in mouse skin. These findings suggest that the NADPH oxidase system of neutrophils rather than the epithelial xanthine oxidase system is dominant for the O2--generating potential in double TPA-treated mouse skin. ACA significantly inhibited mouse epidermis thiobarbituric acid-reacting substance formation, known as an overall oxidative damage biomarker. Moreover, histological studies demonstrated that ACA inhibited double TPA treatment-induced morphological changes reflecting inflammatory response, such as edema formation, leukocyte infiltration, hyperplasia, and cell proliferation. Furthermore, pretreatment with ACA but not 1'-hydroxychavicol in the activation phase inhibits double TPA application-induced increases in both number of leukocytes and proliferating cell nuclear antigen index. These results suggested that ROS from leukocytes including O2- plays an important role for continuous and excessive production of chemotactic factors, leading to chronic inflammation and hyperplasia, which are inhibitable by ACA. Thus, we concluded that O2- generation inhibitors are agents that effectively inhibit oxidative stress and inflammatory responses in mouse skin.

Animals↗
PubMed1996

Expression of Epstein-Barr virus latent infection genes and oncogenes in lymphoma cell lines derived from pyothorax-associated lymphoma.

Malignant lymphomas frequently develop in the pleural cavity of patients with long-standing pyothorax. The term pyothorax-associated lymphoma (PAL) has been proposed for this type of tumor. Most PALs are diffuse lymphomas of the B-cell type and contain Epstein-Barr virus (EBV) DNA. We have established 2 lymphoma cell lines from biopsy specimens of PAL cases, OPL-1 and OPL-2, and examined their growth characteristics and the expression of EBV latent infection genes and oncogenes. OPL-2 exhibited a more rapid growth and higher saturation density than OPL-1, and only OPL-2 exhibited colony-forming activity in soft agar. OPL-1 and -2 were positive for B-cell differentiation markers and showed clonal surface immunoglobulins. Both line contained a single predominant form of episomal EBV DNA, indicating clonal cellular proliferation of an EBV-infected progenitor cell. OPL-1 and -2 contained type B and A EBV genome, respectively. Expression of EBV nuclear antigen (EBNA)2 mRNA and protein was detected by Northern and Western blot analysis in OPL-1, but not in OPL-2. On the other hand, the expression of latent membrane protein (LMP)1 mRNA in both OPL-1 and -2 was extremely weak and detectable only by reverse transcription-polymerase chain reaction. Protein expression of LMP1 was not observed by Western blot analysis or immunocytochemistry. Both lines expressed c-myc mRNA. Only OPL-1 expressed mRNA of c-fgr, an oncogene whose expression is upregulated by EBNA2. Both OPLs expressed bcl-2 mRNA without detectable expression of LMP1 protein.

Aged↗
PubMed1996

[Prospective clinical study of the combination therapy of auranofin and methotrexate for rheumatoid arthritis--a multi-center study].

In a study to evaluate the usefulness of DMARDs combination therapy for RA, AF and MTX were concurrently given to RA patients who had responded poorly to over three months of monotherapy of either AF or MTX. The study was composed of two stages. In the first stage, patients were concurrently given AF and MTX for six months in order to evaluate the efficacy of combination therapy. In the second stage, patients who had responded to the earlier combination therapy were again put on monotherapy of the additive DMARD. Safety evaluation was conducted with 126 patients, and both efficacy and utility were evaluated in 100 patients. Lansbury index for RA significantly improved in both groups of patients starting with the AF and followed by the MTX combination (Group I) and those who started with MTX alone followed by the AF combination (Group II). The ratio of patients who achieved slight improvement or better in the overall improvement rating was significantly higher in Group I at 74.6%, vs. 51.1% in Group II patients. Ten patients (16.9%) and 2 patients (4.9%) were switched to their additive DMARD monotherapy of MTX and AF respectively, having responded to the combination therapy in stage I with slight improvement or a better rating. Adverse events were observed in 44 patients (34.9%), but the combination therapy neither increased the incidence of adverse events nor caused new adverse events. Combination therapy of AF and MTX appeared to be useful both in terms of efficacy and safety for patients who have experienced the dwindling effect of monotherapy.

Adult↗
PubMed1995

[The validity and reliability of a Japanese version of Arthritis Impact Measurement Scales in patients with rheumatoid arthritis].

A Japanese version of Arthritis Impact Measurement Scales (Japanese-AIMS) was developed after the original AIMS Version 2 (AIMS 2). We then conducted a Quality of Life measurement of 691 patients with Rheumatoid Arthritis (RA) with this newly developed questionnaire. Based on the data collected, the validity and reliability of the Japanese-AIMS was examined. The validity of the Japanese-AIMS, which was assessed by the examination of internal consistency among items and through factor analysis, was almost comparable with that of the original AIMS 2. QOL scales were also validated using internal standards based on the subject's responses to other items in the questionnaire. The test-retest reliability, which was the correlation of scale scores between two tests administered 4-5 weeks apart, was slightly lower than the original one. We conclude that the validity and reliability of the Japanese AIMS were comparable with those of the original one, though there could be possibly improved by the minor revision of phrasing. The large scale QOL measurement study with RA patients is under way, using the Japanese-AIMS with minor revision.

Activities of Daily Living↗
PubMed1994

[Mechanism of poor responsiveness to therapy of bacterial infection in patients with connective tissue diseases].

Infectious complications are important factors for poor prognosis of connective tissue diseases (CTD). 33% of the fatal cases with CTD were caused by infectious complications in our study. It was characteristic of infectious complications with CTD, that pneumonia was recognized in all CTD, especially, commoner in PSS, PM and OL, and frequently caused a fatal outcome. Gram negative bacillus, for instance E. coli and K. pneumoniae were frequently detected as pathogens. On the other hand, methicillin resistant Staphylococcus aureus (MRSA) was increased recently, and tuberculosis, especially atypical tuberculosis, such as, miliary and cutaneous forms were also recognized. The risk factors in the development of bacterial infections is considered to be intricately correlated with cellular and humoral immunodeficiency due to CTD or steroid hormones.

Antibody Formation↗
PubMed1993

A cultured skin substitute composed of fibroblasts and keratinocytes with a collagen matrix: preliminary results of clinical trials.

The cultured skin substitute was created through successive cultivation of fibroblasts and keratinocytes that were combined within a collagen matrix. This collagen matrix was composed of a collagen spongy sheet and a collagen gel. The collagen spongy sheet was designed to produce a honeycomb structure having many holes in which all holes through the sheet were filled with collagen gel. This specific structure thereby allows for the nourishment of the cultured keratinocytes on the surface of the matrix when placed on the graft bed. In this study, autologous cultured skin substitute was applied to a 51-year-old man who had sustained a burn injury. Three sheets of the cultured skin substitute (6 x 9.5 cm) were grafted onto the full-thickness excised wound in the right anterior chest wall. One week after grafting most of the matrix disappeared and stratified keratinocytes were seen to have firmly attached to the underlying tissue. Five weeks after grafting a cornified epidermal layer was seen. Ten months after grafting a mature epidermis and a well-differentiated papillary and reticular dermis replacement were observed. The physical properties and color of this grafted area resemble those of normal skin. In the second test case, autologous cultured skin substitute was applied to a 30-year-old man with a scar remaining after tattoo removal. Eight sheets of the cultured skin substitute (10 x 18 cm) were applied on an excised wound (thickness, 0.02-0.025 in.) of both the fore- and upper arms. The histological appearance of a biopsied skin specimen from the grafted area at 3 months after grafting showed a mature epidermis and a well-differentiated reticular dermis replacement. The regenerated skin at 14 months after grafting showed an excellent result.

Adult↗
PubMed1993

[A case of Legionnaires' disease due to aspiration of hot spring water and isolation of Legionella pneumophila from hot spring water].

We report a case of fulminant pneumonia that was due to aspiration of contaminated hot spring water and was not affected by beta-lactam antibiotics. We suspected that the patient had Legionnaires' disease and treated the clinical symptoms with erythromycin. Legionellaceae could not be isolated from sputum or lung biopsy material, but an elevated titer to Legionella pneumophila serogroup 4 was found by indirect immunofluorescence test. We diagnosed the patent as having Legionnaires' disease with improved clinical symptoms. Furthermore, we went to the hot spring that he visited and tried to isolate Legionellaceae. Hot spring water was collected from the bathroom and water, hot water, and shower water from the guest-room. After using a low-pH method, samples were cultured on BCYE alpha medium. Serogroups are classified by agglutination method with immune rabbit serum. As a result, we successfully isolated Legionella pneumophila serogroup 4 from hot spring water (42 degrees C) from the bath. No bacteria could be isolated from the other samples. Therefore, we believe that this case of Legionnaires' disease was caused by aspiration of contaminated hot spring water. The infection route of Legionnaires' disease is unclear. There are no previous reports of isolation of Legionellaceae from Japanese hot springs. This case would provide important information when considering the infection route of Legionnaires' disease in Japan.

Accidents↗
PubMed1993

The effects of warfarin on calcinosis in a patient with systemic sclerosis.

We describe the use of low doses of warfarin to treat calcinosis in a patient with systemic sclerosis or CREST syndrome. Our patient had Raynaud's phenomenon, skin sclerosis of the neck and the distal surface of the elbows, and pitting ulcers and scarification of the fingers as well as cutaneous calcinosis. After beginning warfarin, no calcium containing substance was discharged from the fingertip ulcers. There was no tendency to bleed and activated partial thromboplastin time and prothrombin time were normal. Sequential radiographs of the hands showed that calcinosis had improved. Since there seem to be few adverse effects, the use of warfarin in patients with calcinosis warrants further study.

Calcinosis↗