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Biomedical subjects

M Sasano

Publications and source records attributed to M Sasano.

At least 19 recordsLinked to original sources
PubMed1992

Constitutive production of angiotensin converting enzyme from rheumatoid nodule cells under serum free conditions.

Angiotensin converting enzyme was assayed in serum free culture supernatants from unstimulated rheumatoid nodule cells. Angiotensin converting enzyme was released spontaneously and the angiotensin converting enzyme derived from rheumatoid nodule cells was suppressed in a dose and time dependent manner by the protein synthesis inhibitor cycloheximide. These data suggest the constitutive de novo synthesis of angiotensin converting enzyme by rheumatoid nodule cells.

Adult↗
PubMed1992

Inhibitory effect of (4R)-hexahydro-7,7-dimethyl-6-oxo-1,2,5-dithiazocine-4-carboxylic acid (SA3443), a novel cyclic disulfide, on the production of TNF-like factor from Propionibacterium acnes-primed rat liver macrophages/Kupffer cells.

The effect of (4R)-hexahydro-7,7-dimethyl-6-oxo-1,2,5-dithiazocine-4-carboxylic acid (SA3443), a novel cyclic disulfide, on tumor necrosis factor (TNF)-like factor production from Propionibacterium acnes (P. acnes)-primed rat liver macrophages/Kupffer cells was investigated. A remarkable increase in TNF-like activity was detected in the culture supernatants of the liver macrophages/Kupffer cells from P. acnes-treated rats. At concentrations of 1 x 10(-6) to 1 x 10(-4) M, SA3443 significantly inhibited the production/release of TNF-like factor from these P. acnes-primed/activated liver macrophages/Kupffer cells.

Adjuvants, Immunologic↗
PubMed1991

Suppressive effect of anti-rheumatic drugs on interleukin-1 beta release from human peripheral blood monocytes.

We developed an ELISA system for human IL-1 alpha and -beta release from silica-stimulated monocytes from healthy volunteers and tested the effect of several anti-rheumatic drugs including nonsteroidal anti-inflammatory drug (Ibuprofen). Anti-rheumatic drugs including Auranofin and Sulphasalazine suppressed IL-1 beta release significantly at therapeutic concentrations, whereas Bucillamine, Lobenzarit, D-Penicillamine and Ibuprofen did not. These results suggest a possible immunotherapeutic effectiveness of some anti-rheumatic drugs on rheumatoid arthritis through their inhibition of IL-1 beta release.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1991

Interleukin-1 beta release from human peripheral blood monocytes associated with phagocytosis of carbonyl-iron or erythrocytes.

Interleukin-1 beta (IL-1 beta) release from human peripheral blood monocytes during the incubation with carbonyl-iron or sheep red blood cells was investigated. The incubation of purified monocytes with carbonyl-iron or sheep red blood cells enhanced IL-1 beta release, while their compounds, hemoglobin, globin and ferric citrate did not. The mechanisms of IL-1 beta release by carbonyl-iron or sheep red blood cells may be related to their phagocytosis, as non-phagocytic monocytes did not release IL-1 beta.

Enzyme-Linked Immunosorbent Assay↗
PubMed1991

Functional characterization of SV40-transformed adherent synovial cells from rheumatoid arthritis.

A total of 14 transformed cell clones were obtained by micro-injecting origin-defective SV40 DNA into three types of cloned adherent synovial cells (ASC) (dendritic cells (DCs), macrophage-like cells (MCs), and fibroblast-like cells (FCs)) from two rheumatoid arthritis patients (five DC clones (SV40-DCs), five MC clones (SV40-MCs) and four FC clones (SV40-FCs)). All the transformed cell nuclei expressed SV40-specific T antigen. The cells which formed a colony had a few times shorter doubling time than the original cells. IL-1 alpha, IL-1 beta and prostaglandin E2 were detected in the culture supernatant from the unstimulated transformed cells like untransformed cells. The SV40-DCs showed the most potent accessory cell function in oxidative mitogenesis assay among the three types of SV40-ASCs. Granulocyte macrophage colony stimulatory factor (GM-CSF) was detected only in the culture supernatant from the SV40-MCs without stimulation. Extensive phenotypic analysis revealed relatively cell-specific markers. SV40-DCs were HLA-DP+ and glial fibrillary acidic protein positive. SV40-MCs stained positive for 5'-nucleotidase and nonspecific esterase. These transformed ASCs retained much of the original cellular physiology of rheumatoid arthritis (RA) ASCs and may be a useful tool for characterizing the role of ASCs in the pathogenesis of RA.

Adult↗
PubMed1991

Induction of cytotoxic cell activities by a novel cyclic disulfide compound, SA3443 in vivo.

(4R)-Hexahydro-7,7-dimethyl-6-oxo-1,2,5-dithiazocine-4-carboxylic acid (SA3443) is a newly synthesized cyclic disulfide compound which offers potential hepatoprotective properties. The effect of SA3443 on the induction of natural killer (NK) and cytotoxic T lymphocyte (CTL) activities was investigated. NK activity in BALB/c mice splenic cells was investigated using YAC-1 cells as target cells. SA3443, at a dose range of 30-300 mg/kg/day, augmented NK activity significantly when administered orally once daily for 4 days before the assay. Alloantigen-specific CTL activity in splenic cells from BALB/c mice was detected 9 days after sensitization with C57BL/6 mice splenic detected 9 days after sensitization with C57BL/6 mice splenic cells. SA3443, at a dose of 100 mg/kg/day, augmented CTL activity significantly when administered orally, once daily for 4 days beginning after the sensitization and for 2 days before the assay, while a high dose of SA3443, at 300 mg/kg, suppressed CTL activity. From these results, it is thought that SA3443 may assist in the elimination of hepatitis viruses from the liver in patients with chronic active hepatitis, by the activation of NK and/or CTL activities.

Adjuvants, Immunologic↗
PubMed1991

SA3443, a novel cyclic disulfide compound, depresses anti-SRBC antibody-forming cell responses in the mouse through inhibition of antigen-presenting cell activities.

(4R)-Hexahydro-7,7-dimethyl-6-oxo-1,2,5-dithiazocine-4-carboxylic acid (SA3443) is a newly synthesized cyclic disulfide compound which has potential hepatoprotective properties. The effect of SA3443 on the induction of anti-sheep red blood cell (SRBC) plaque (antibody) forming cell (PFC) responses was investigated in vivo and in vitro. SA3443 (approximately 3 mg/kg/day) remarkably decreased the number of anti-SRBC PFC in the spleens of mice immunized with a high dose of SRBC in vivo. The addition of SA3443 (approximately 1 x 10(-7) M) at the initiation of mouse spleen cell cultures in vitro also exerted a significant inhibitory effect on subsequent PFC response to SRBC, and removal of SA3443 after 24 h did not reverse its inhibitory effect. Pre-incubation of isolated adherent spleen cells with SRBC and SA3443 resulted in a similar inhibition of subsequent PFC response, but a pre-incubation of macrophage-depleted cells with SRBC and SA3443 or a pre-incubation of the unseparated spleen cells with SA3443 in the absence of SRBC had no effect. These findings have suggested that SA3443 may depress antibody response through inhibition of macrophage antigen-presenting cell activity.

Adjuvants, Immunologic↗
PubMed1990

Modulatory effect of bucillamine (SA96) on interleukin-1-and/or -2-induced proliferation of T lymphocytes.

Bucillamine [SA96:N-(2-mercapto-2-methylpropanoyl)-L-cysteine], a synthetic SH compound, has recently been developed as remission-inducing agent for rheumatoid arthritis (RA), and its clinical usefulness for RA has been proved in Japan. Bucillamine suppressed the mitogen-induced proliferation of murine lymphocytes in vitro. The present study was undertaken to clarify the effect of bucillamine primarily on the release of interleukin (IL)-1 from monocytes and on the proliferation of T cells. Bucillamine significantly inhibited IL-1-induced thymocyte proliferation in a dose-dependent manner. And, bucillamine also inhibited IL-2-induced proliferation at the concentration of 1 x 10(-4) M, but augmented proliferation at the concentration of 1 x 10(-5) M. In contrast, D-penicillamine (an analogous SH compound to bucillamine) did not show any significant effect at similar concentrations.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1990

Spontaneous release of angiotensin converting enzyme and interleukin 1 beta from peripheral blood monocytes from patients with rheumatoid arthritis under a serum free condition.

Angiotensin converting enzyme (ACE) and interleukin 1 activities were assayed simultaneously in the serum free medium from the unstimulated peripheral blood monocytes from 32 patients with rheumatoid arthritis (RA), 11 patients with osteoarthritis, and 25 normal controls matched for age and sex. Angiotensin converting enzyme activity was raised in most (29/32) patients with RA and interleukin 1 activity (most of which was interleukin 1 beta) was enhanced in 11/32 patients with RA, while monocytes from only two patients with osteoarthritis, but from none of the controls, secreted a small amount of ACE alone in the culture condition. Monocytes from patients with early RA (disease duration less than 3 years) released significantly more ACE and interleukin 1 than those from late stage RA (disease duration greater than or equal to 3 years).

Adult↗
PubMed1990

Production of prostaglandin E2 induced by histamine by cloned rheumatoid synovial cells.

Production of prostaglandin E2, with or without histamine stimulation, by three different types of cloned rheumatoid synovial cells (macrophage like, dendritic, and fibroblast like) was evaluated. The ability of these cloned cells to respond to histamine on a cell to cell basis was as follows: macrophage like cells responded most strongly, followed by dendritic cells, followed by fibroblast like cells. Production of prostaglandin E2, stimulated by histamine, may have a role in bony destruction in rheumatoid joints.

Adult↗
PubMed1990

Adherent synovial cells from nonrheumatoid arthritis do not release interleukin 1 beta and prostaglandin E2 spontaneously in longterm culture.

Adherent synovial cells from both 13 patients without rheumatoid arthritis (RA) (gout, osteoarthritis and meniscal lesion) and 8 patients with RA consisted of dendritic cells, macrophage-like cells and fibroblast-like cells after cloning in a similar fashion as reported in our previous paper. All the adherent synovial cells from patients without RA did not release interleukin 1 (IL-1) beta and prostaglandin E2 (PGE2) spontaneously, while those cells released comparable amounts of IL-1 beta, but not PGE2 to RA cells after type II collagen stimulation. Only the synovial cells from RA, irrespective of morphology and cloning, released IL-1 beta and PGE2 without stimulation. Nonrheumatoid synovial cells may differ functionally from RA cells.

Arthritis, Rheumatoid↗
PubMed1989

Decrease in disease activity and concomitant increase in the percentage of peripheral blood suppressor T-cells in rheumatoid arthritis by a newly synthesized slow-acting anti-rheumatic drug (Bucillamine).

Bucillamine: N-(2-mercapto-2-methyl-propanoyl)-L-cysteine, is a newly synthesized slow-acting anti-rheumatic drug with two SH-bonds in its chemical structure. Eleven patients with rheumatoid arthritis (RA) were treated with Bucillamine, and both Lansbury's activity index and the percentage of suppressor T-cells (Leu 2a+ Leu 15+) were serially monitored for 10 weeks. The percentage of suppressor T-cells, which was depressed in the active disease state, reached normal levels with clinical improvement according to Lansbury's index. Bucillamine may have an immunomodulating activity and may be a useful drug for the treatment of RA.

Adult↗
PubMed1989

Lack of association of HLA-DR4 with interleukin 1 beta secretion from peripheral blood monocytes in patients with rheumatoid arthritis.

The possible association between HLA-DR4 and interleukin 1 beta (IL-1 beta) secretion from peripheral blood monocytes was analyzed using 34 female patients, with definite rheumatoid arthritis (RA). RA monocytes in serum-free medium or medium supplemented with 10% fetal calf serum secreted IL-1 spontaneously. The level of secretion was enhanced by stimulation with pyrogen-free type II collagen as determined by comparison with 30 healthy individuals matched for age and sex. No association between HLA-DR4 and spontaneous or stimulated IL-1 release from RA monocytes was observed.

Adult↗
PubMed1988

Augmented interleukin-1 production and HLA-DR expression in the synovium of rheumatoid arthritis patients. Possible involvement in joint destruction.

Potent interleukin-1 (IL-1) activity was detected in culture supernatants from synovium, obtained by arthroscopy, from rheumatoid arthritis (RA) patients but not from non-RA patients. Production of IL-1 by RA synovium correlated well with findings of inflammation on arthroscopy and HLA-DR expression in immunohistochemical staining. Furthermore, there was a positive correlation between IL-1 production from RA synovium and joint changes detected on roentgenograms. These findings strongly suggest that IL-1 might play an important role in the joint destruction in RA.

Adult↗
PubMed1988

Stimulation of interleukin-1 alpha and interleukin-1 beta release from human monocytes by cyanogen bromide peptides of type II collagen.

Pyrogen-free cartilage fragments from patients with fracture, osteoarthritis, or rheumatoid arthritis were found to stimulate the production of interleukin-1 alpha-like and interleukin-1 beta-like factor by peripheral blood mononuclear cells from healthy individuals and rheumatoid arthritis patients. The stimulatory cartilaginous component was type II collagen, and the major stimulatory determinant on type II collagen was found to be cyanogen bromide 11 peptide. These results suggest a possible pathogenic role of the intact cartilaginous component in interleukin-1-mediated joint destruction.

Arthritis, Rheumatoid↗
PubMed1988

pH dependency of effect of topically applied dipivefrine hydrochloride on intraocular pressure and pupil size in rabbits: comparative studies with epinephrine.

The pH and dose dependencies of topically applied dipivefrine hydrochloride (DPE) on intraocular pressure (IOP) reduction and mydriasis were compared with those of epinephrine bitartrate (EPI) in normal rabbits. Statistically significantly greater IOP lowering and mydriatic effects of DPE solutions were achieved by increasing their pH from 3 to 6 or their concentrations from 0.02% to 0.1%. The ocular hypotensive and mydriatic effects of EPI also depended on their concentrations, but not on their pH. On the other hand, blink rates of rabbits following topical application of DPE tended to be reduced by the increase of pH, while they were not influenced by the concentrations. From these results, it was indicated that the pharmacological effects of DPE were augmented about 3 times by increasing the pH of its solutions from 3 to 5, which also was associated with reduction of ocular irritation, while the effects of EPI were not altered by the changes of pH. As the result of the increase of pH from 3 to 5, DPE became about 50 times more potent than EPI as a ocular hypotensive agent.

Administration, Topical↗
PubMed1987

Spontaneous production of an interleukin 1-like factor by cloned rheumatoid synovial cells in long-term culture.

We have cloned adherent synovial cells from rheumatoid synovitis. These can be generally divided into three types, including cells that have the characteristic features of dendritic cells (DCs), macrophagelike cells (MCs) and fibroblastlike cells (FCs), as classified by morphology and immunofluorescent staining. The cloned cells were able to divide and were cultured for up to 11 mo without any significant morphological changes. All the cloned cells were HLA-DR+ after gamma-interferon treatment. Spontaneous production of a factor with interleukin 1 activity by the cloned cells was detected even after long-term culture (the ability, on a per cell basis, being in the following order: DC greater than MC greater than FC). These synovial cells may be important for bony destruction in rheumatoid joints.

Arthritis, Rheumatoid↗