Biomedical subjects

M Sasano

Publications and source records attributed to M Sasano.

At least 19 recordsLinked to original sources

PubMed2006

Spin correlations of strongly interacting massive fermion pairs as a test of Bell's inequality.

We report the results of the first-time test of the local hidden variable theories (Bell-Clauser-Horne-Shimony-Holt) involving strongly interacting pairs of massive spin 1/2 hadrons from the decay of short-lived (tau<10;-21sec) 2He spin-singlet state, populated in the nuclear reaction 2H+;1H-->;2He+n. The novel features of this experiment are (a) the use of an 'event-ready' [corrected] detector of nearly 100% efficiency to prepare an unbiased sample and (b) a focal-plane polarimeter of full 2pi sr acceptance with a random "post selection" of the reference axes. The spin-correlation function is deduced to be S[exp](pi/4)=2.83+/-0.24stat+/-0.07sys. This result is in agreement with nonlocal quantum mechanical prediction and it violates the Bell-CHSH inequality of |S|<or=2 at a confidence level of 99.3%.

Journal Article↗

PubMed2005

Resolving the discrepancy of 135 MeV pd elastic scattering cross sections and relativistic effects.

Three precise measurements for elastic pd scattering at 135 MeV/A have been performed with the three different experimental setups. The cross sections are described well by the theoretical predictions based on modern nucleon-nucleon forces combined with three-nucleon forces. Relativistic Faddeev calculations show that relativistic effects are restricted to backward angles. This result supports the two measurements recently reported by RIKEN and contradicts the KVI data.

Journal Article↗

PubMed2000

Effects of combinations of anti-rheumatic drugs on the production of vascular endothelial growth factor and basic fibroblast growth factor in cultured synoviocytes and patients with rheumatoid arthritis.

OBJECTIVE: To examine whether different combinations of disease-modifying anti-rheumatic drugs (DMARDs), including bucillamine (BUC), gold sodium thiomalate (GST), methotrexate (MTX), salazosulphapyridine (SASP) and dexamethasone (DEX; a steroid), act by inhibiting the production of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in cultured synoviocytes, causing a decrease in their serum concentrations in patients with rheumatoid arthritis (RA). METHODS: The VEGF and bFGF concentrations in cultured synoviocytes and peripheral blood from patients with RA were measured by enzyme-linked immunosorbent assay and their serum concentrations were measured at two time points. RESULTS: BUC and GST inhibited VEGF production even when given alone, and a combination of BUC, GST and MTX with DEX also inhibited VEGF production. None of the DMARDs or DEX inhibited bFGF production when given alone, but a combination of SASP and GST inhibited the production of bFGF in cultured synoviocytes. Serum VEGF concentrations were significantly decreased 6 months after the commencement of medication compared with their concentrations before medication. CONCLUSION: Our results show that the effects of a combination of DEX with any two of BUC, GST, SASP and MTX on the production of VEGF and bFGF in cultured synoviocytes and on the serum concentrations of VEGF in patients with RA may be based on synergistic or additive effects of the drugs.

Anti-Inflammatory Agents↗

PubMed1999

Inhibitory effects of anti-rheumatic drugs on vascular endothelial growth factor in cultured rheumatoid synovial cells.

Vascular endothelial growth factor (VEGF) is a potent inducer of angiogenesis and is constitutively expressed in the synovium of rheumatoid arthritis (RA). Over-expression of VEGF may play an important role in pathogenic vascularization and synovial hyperplasia of RA. In the present study, we examined whether disease-modifying anti-rheumatic drugs (DMARDs), including bucillamine (BUC), gold sodium thiomalate (GST), methotrexate (MTX) and salazosulfapiridine (SASP), act by inhibiting the production of VEGF by cultured synovial cells of patients with RA. Treatment of cultured synoviocytes with lipopolysaccharide (LPS) significantly increased VEGF production by cultured synovial cells. BUC significantly inhibited LPS-induced VEGF production, while GST tended to inhibit the production of VEGF. The inhibitory effects on VEGF production were dose-dependent. In contrast, MTX and SASP did not affect VEGF production. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis showed that BUC also inhibited LPS-induced VEGF mRNA expression in RA synovial cells. The present study provides the first evidence that BUC inhibits VEGF production and the expression of its mRNA in synovial cells of RA patients. Our results indicate that the anti-rheumatic effects of BUC are mediated by suppression of angiogenesis and synovial proliferation in the RA synovium through the inhibition of VEGF production by synovial cells.

Antirheumatic Agents↗

PubMed1997

Salazosulfapyridine suppresses chondrocyte mediated degradation induced by interleukin 1beta.

OBJECTIVE: To investigate the effects of salazosulfapyridine (SASP) and methotrexate (MTX) on interleukin (IL)-1beta treated rabbit chondrocytes. METHODS: Normal rabbit chondrocytes were cultured to confluency. IL-1beta was added to serum-free culture medium in the presence or absence of SASP or MTX. After 2 days' incubation, the effects were evaluated from the responses of metalloproteinases, glycosaminoglycan (GAG), and prostaglandin E2 (PGE2). RESULTS: SASP and MTX suppressed GAG and collagenase release into the culture medium from IL-1beta stimulated rabbit chondrocytes in a dose dependent manner. Only SASP suppressed stromelysin and PGE2 release. CONCLUSION: SASP may have a protective effect on cartilage degradation of patients with rheumatoid arthritis.

Animals↗

PubMed1997

Amelioration of type II collagen induced arthritis in rats by treatment with thymulin.

OBJECTIVE: To investigate the effects of thymulin (serum thymic factor + Zn2+) in collagen induced arthritis (CIA) in rats. METHODS: SD rats were immunized with bovine type II collagen plus Freund's incomplete adjuvant, and thymulin was administered intraperitoneally on the first day of first immunization. We determined the level of serum thymulin by rosette inhibition assay. Effects of thymulin on CIA rats were estimated by measuring the extent of hind paw edema, the level of serum anti-type II collagen antibody, and changes in histopathological features of the affected joints. RESULTS: Serum thymulin levels in CIA rats were significantly lower than in untreated rats. Thymulin diminished hind paw swelling and onset of arthritis compared with control rats. The serum anti-type II collagen antibody level was also reduced by thymulin. Histopathological examination showed inhibition of granulation tissue and new bone formation after injection of thymulin. CONCLUSION: Our results suggest thymulin plays a significant role in the onset and development of CIA in rats. Our data indicate thymulin may be therapeutically effective in preventing the development of rheumatoid arthritis.

Animals↗

PubMed1995

Superantigen properties of a human sialoprotein involved in gut-associated immunity.

Protein Fv (pFv) is a recently described 175-kD gut-associated sialoprotein with a potent capacity for augmentation of antibody-dependent immune functions. To investigate the molecular basis for Fab-mediated binding of pFv, we evaluated a panel of 52 monoclonal IgM and found that approximately 40% bound pFv. Whereas the majority (> or = 75%) of V H3 and V H6 IgM strongly bound pFv, only a small minority (< 20%) of IgM from other V H families bound pFv, and these antibodies had weaker binding interactions. Inhibition studies suggested that all binding occurred at the same (or overlapping) site(s) on pFv. Surface plasmon resonance studies demonstrated binding affinity constants up to 6.7 x 10(8) M-1 for pFv. Biopanning of IgM and IgG Fab phage-display libraries with pFv preferentially selected for V H3 and V H6 antibodies, but also obtained certain V H4 IgM. V H sequence analyses of 36 pFv-binding antibodies revealed that binding did not correlate with CDR sequence, JH, or L chain usage. However, there was preferential selection of pFv binders with V H CDR3 of small size. These studies demonstrate that a protein which enhances immune defense in the gut has structural and functional properties similar to known superantigens.

Amino Acid Sequence↗

PubMed1993

Age-associated changes in binding of human B lymphocytes to a VH3-restricted unconventional bacterial antigen.

We have recently demonstrated that there is a site on Staphylococcal protein A (SpA) that interacts with B cell Ig receptors in a manner comparable with known T cell superantigens, because this binding specificity is restricted to Fab with VH3 H chains and most VH3 Ig bind SpA. In the present studies, SpA was used as a phenotypic marker for VH3 expression by human lymphoid cells. As expected, this Fab-mediated binding specificity was completely inhibited by certain VH3 antibodies but not by antibodies from other VH families. In multiparameter flow cytometric analyses, this binding activity was demonstrated to be highly prevalent among B cells (14 to 54%), and was more common among IgM-bearing B cells compared with IgG-bearing B cells. In all studies, Fab-mediated binding of SpA was uniformly expressed by a greater proportion of CD5-positive B cells than CD5-negative B cells. The proportion of B lymphocytes with this VH3-restricted binding capacity was found to undergo age-associated changes, because a large proportion of the peripheral B cells of neonates (mean +/- SD, 46.0 +/- 2.9%) bind this site, but two 10-mo-old subjects and older children had significantly lower binding levels (29.0 +/- 3.5%) that were the same as binding levels by adult peripheral B lymphocytes (30.2 +/- 3.3%). In immunohistochemical studies, tonsilar B cells that bind this site on SpA were shown to be common in mantle zones and germinal centers of secondary follicles. We speculate that Fab-mediated SpA binding represents a fundamental and primitive binding capacity that is part of the human preimmune repertoire, and we discuss the implications for the observed age-dependent shift in Fab-mediated binding of SpA by peripheral blood B cells.

Adult↗

PubMed1993

Molecular selection of human antibodies with an unconventional bacterial B cell antigen.

Unconventional Ag for B cells that are comparable to known superantigens for T lymphocytes have not been well characterized. However, the bacterial membrane protein, Staphylococcal protein A (SpA), has sites that interact with the Fab of many IgM, IgA, IgG, and IgE, and in recent reports we have provided evidence of VH restriction in Fab that bind SpA. To investigate the molecular basis for this Fab binding specificity, we have selected monoclonal Fab from a phage-display combinatorial Ig library, based on the ability to bind SpA. By this approach, in an unselected human polyclonal IgG Fab library, about 17% of antibody-expressing clones were found to bind SpA. SpA binding was completely restricted to Fab with VH3 H chains, and about 60% of VH3 Fab in the unselected library had SpA binding capacity. Analysis of 21 VH sequences and 6 VL sequences demonstrated that Fab that bind SpA use diverse VH3 genes, while the L chains derive from a variety of V kappa and V lambda gene families. By creation of antibodies with differential H-L chain pairing, the global capacity to bind SpA was shown to be dictated by VH3 usage, but different L chain usage could result in up to a fourfold change in binding affinity. The apparent KD of the SpA binding by different Fab ranged from 2.5 x 10(-7) to > 10(-5) M. Furthermore, repeated rounds of in vitro panning selected for antibodies based on higher binding affinity. These data indicate that the pattern of VH family restriction of Ig reactive with SpA is comparable to known superantigens, and there is a hierarchy within the binding affinities of VH3 Fab based on V gene usage.

Adult↗

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↗