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Biomedical subjects

M Shingu

Publications and source records attributed to M Shingu.

At least 19 recordsLinked to original sources

Spontaneous formation of vanadium "molecules" in a geometrically frustrated crystal: AlV2O4.

We investigated the charge-ordered (CO) state in spinel AlV2O4 by electron diffraction, synchrotron x-ray diffraction, and magnetic measurements. It was found that the CO structure appearing below 700 K is characterized by the formation of V clusters (heptamers), each of which is consisting of 7 vanadium atoms and is in a spin-singlet state as a total. Theoretical consideration indicates that this unique molecularlike V heptamer is stabilized by a strong bonding of vanadium t(2g) orbitals.

Journal Article↗

Spondyloarthropathies in Japan: nationwide questionnaire survey performed by the Japan Ankylosing Spondylitis Society.

OBJECTIVE: The Japan Ankylosing Spondylitis Society conducted a nationwide questionnaire survey of spondyloarthropathies (SpA) in 1990 and 1997, (1) to estimate the prevalence and incidence, and (2) to validate the criteria of Amor and the European Spondylarthropathy Study Group (ESSG) in Japan. METHODS: Japan was divided into 9 districts, to each of which a survey supervisor was assigned. According to unified criteria, each supervisor selected all the clinics and hospitals with potential for SpA patients in the district. The study population consisted of all patients with SpA seen at these institutes during a 5 year period (1985-89) for the 1st survey and a 7 year period (1990-96) for the 2nd survey. RESULTS: The 1st survey recruited 426 and the 2nd survey 638 cases, 74 of which were registered in both studies. The total number of patients with SpA identified 1985-96 was 990 (760 men, 227 women). They consisted of patients with ankylosing spondylitis (68.3%), psoriatic arthritis (12.7%), reactive arthritis (4.0%), undifferentiated SpA (5.4%), inflammatory bowel disease (2.2%), pustulosis palmaris et plantaris (4.7%), and others (polyenthesitis, etc.) (0.8%). The maximum onset number per year was 49. With the assumption that at least one-tenth of the Japanese population with SpA was recruited, incidence and prevalence were estimated not to exceed 0.48/100,000 and 9.5/100,000 person-years, respectively. The sensitivity was 84.0% for Amor criteria and 84.6 for ESSG criteria. CONCLUSION: The incidence and prevalence of SpA in Japanese were estimated to be less than 1/10 and 1/200, respectively, of those among Caucasians. The adaptability of the Amor and ESSG criteria was validated for the Japanese population.

Adult↗

Studies of bovine enterovirus structure by ultraviolet resonance Raman spectroscopy.

The structural comparison of bovine enterovirus MZ468 strain before and after the heat treatment was studied by ultraviolet resonance Raman (UVRR) spectra excited at both 235 and 251 nm. The difference between full, heated full and purified empty particles, which were expected as an in vitro model of uncoating, were demonstrated. At 235 nm excitation, the Raman bands of the capsid protein dominated in all the UVRR spectra. The UVRR spectra of the empty particles exhibited non-homogenious broadening for tryptophan W3 band and W7 Fermi doublet bands, which were characteristics of hydrophobic environment, when compared with those of the full particles. The results indicates that some Trp indole rings of the full particles were packaged inside the viral capsids and not strained by virion assembly. On the other hand, the Raman bands assigned to guanine residues of the single stranded-RNA genome were enhanced strongly in the 251-nm excited UVRR spectrum. The spectral differences between the packaged (full particles) and the unpackaged virions (heated full particles) indicates that some guanine residues had strong hydrogen bonds in the full particles.

Animals↗

Nucleotide sequence of the gene encoding the RNA polymerase and the 3' non-coding region of a bovine enterovirus Japanese isolate: rapid synonymous substitutions between European and Japanese strains.

The nucleotide sequences of the genome RNA encoding the RNA polymerase and the 3' non-coding region (NCR) of bovine enterovirus (BEV) serotype I Japanese isolate, MZ468, were determined. The genetic distance between the two BEV serotype I strains, MZ468 and VG-5-27, was calculated by pairwise comparison of nucleotide sequences. The synonymous substitution rate was high (1.40 x 10(-2)/site/year), and of the same order as those of influenza virus HA, HIV-1 gag and env, and enterovirus 70 VP1 genes.

Amino Acid Sequence↗

Anti-inflammatory activity of superoxide dismutase conjugated with sodium hyaluronate.

Superoxide dismutase (SOD) from bovine erythrocytes was conjugated with sodium hyaluronate (HA) with a mean molecular weight of 10(6) to have greater anti-inflammatory activity in vivo. Amino groups of SOD were coupled with carboxyl groups in the hyaluronate molecule using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide. The HA-SOD conjugate was composed of 1.5 mol of SOD molecule per 1 mol of hyaluronate on the average, and retained 70% of the activity of unmodified SOD. The conjugate was essentially non-immunogenic in mice, and exhibited much higher anti-inflammatory activities than HA or SOD in models of inflammatory diseases such as ischemic oedema of the foot-pad in mice, carrageenin-induced pleurisy and adjuvant arthritis in rats.

Animals↗

Nucleic acid binding by zinc finger-like motif of human papillomavirus type 16 E7 oncoprotein.

Human papillomavirus (HPV) types 16 and 6b E7 proteins and their chimeric or mutant proteins were analyzed for oligonucleotide-binding activity by surface plasmon resonance-based biomolecular interaction analysis. The results indicated that type 16 E7 protein has stronger nucleic acid-binding activity than that of type 6b E7 protein. In addition, the results also indicated that the zinc finger-like motif in the C-terminal region of the type 16 E7 protein plays an important role in this activity.

Binding Sites↗

Human monoclonal rheumatoid factors augment arthritis in mice by the activation of T cells.

In order to investigate the in vivo role of rheumatoid factor (RF), the effects of the administration of human monoclonal (m) IgM-RF and IgG-RF on the development of arthritis in mice were examined. The administration of human mRFs into mice immunized with type II collagen (CII) markedly enhanced the clinical score and paw swelling. The severity of arthritic joint disease with a marked infiltration of lymphoid cells, proliferation of synovial membrane, pannus formation and destruction of articular cartilage was significantly enhanced in both groups receiving RF (RF-enhanced arthritis). Skin ulcers were also observed in some of these RF-enhanced arthritis mice, whereas no such signs were observed in CII-immunized mice without mRFs. Both IgM-RF and IgG-RF increased CII-specific IgG antibodies in circulation, and the severity of arthritis correlated with the production of high titres of anti-CII antibodies. In vivo treatment of RF-enhanced arthritis mice with an anti-CD4 MoAb or an anti-CD8 MoAb inhibited the induction and progression of arthritis in these mice. Administration of RF to severe combined immunodeficient (SCID) mice with arthritis developed by the transfer of spleen cells from CII-immunized mice, prolonged the arthritis and enhanced the severity. This murine model of RF-enhanced arthritis may provide a useful tool for analysing the pathogenesis of rheumatoid arthritis in RF-positive patients.

Adoptive Transfer↗

Bone resorption by tartrate-resistant acid phosphatase-positive multinuclear cells isolated from rheumatoid synovium.

Inflammatory reactions in rheumatoid arthritis (RA) often cause severe joint destruction. However, the mechanism of bone destruction is still a matter of controversy. To determine whether multinuclear cells found in the rheumatoid synovium can resorb bone, isolated synovial cells were assessed for tartrate-resistant acid phosphatase (TRAP) staining and the ability to resorb bone in a dentine resorption assay. TRAP-positive multinuclear cells were found in six out of 10 samples. These six samples showed resorption pit formation on dentine slices. The other four samples did not form resorption pits. The results of this study demonstrate that TRAP-positive multinuclear cells isolated from the rheumatoid synovium form resorption pits on dentine slices. Our results suggest that inflamed synovial cells in rheumatoid joints might participate in bone destruction.

Acid Phosphatase↗

HTLV-I infections in offspring derived from HTLV-I carrier rats during the suckling period.

An experimental rat model for vertical transmission of human T cell leukemia virus type I (HTLV-I) was used to examine whether the infection of offspring derived from HTLV-I carrier rats could be established during the suckling period. MT-2 (2 x 10(7)) cells were injected into 5-week-old rats twice, at 2-week intervals. HTLV-I infected or non-infected female rats were mated with HTLV-I carrier male rats. The titer of serum antibodies against HTLV-I in the offspring derived from non-infected dams was less than 1:16 by the agglutination test during the suckling period. The serum antibodies of the offspring derived from the infected dams was less than 1:32 at 1 day after birth and increased steadily to 1:2048 at 14 days. However, the HTLV-I proviral sequences were not detected in any organs of the offspring during the suckling period as determined by the nested double polymerase chain reaction (PCR). These findings indicate that maternal antibodies against HTLV-I were not readily transmitted through the placenta and that the anti-HTLV-I antibodies in the offspring came from the milk of the dams. Furthermore, the HTLV-I infection in the offspring that was derived from the carrier dam may not be established during the suckling period but after weaning.

Animals↗

Increased IL-1 receptor antagonist (IL-1ra) production and decreased IL-1 beta/IL-1ra ratio in mononuclear cells from rheumatoid arthritis patients.

In order to investigate the possible role of IL-1 receptor antagonist (IL-1ra) in patients with rheumatoid arthritis (RA), this study was undertaken to measure the amounts of IL-1ra and interleukin-1 beta (IL-1 beta) protein produced by mononuclear cells (MNC) and to investigate the relationship between production of these cytokines and clinical parameters. The MNC were cultured for 24 h and the supernatants were measured for IL-1ra and IL-1 beta by ELISA kits. MNC from peripheral blood (PB) and synovial fluid of RA patients produced significantly higher amounts of IL-1ra than normal PBMNC (P < 0.01 and P < 0.05, respectively). When the IL-1 beta/IL-1ra ratio was calculated, IL-1 beta/IL-1ra ratios of RA PBMNC were significantly lower than those of normal PBMNC (P < 0.001). The IL-1 beta/IL-1ra ratio of RA PBMNC was significantly higher in active RA patients than in RA patients in remission (P < 0.02). The amounts of IL-1ra produced by stimulated RA PBMNC positively correlated with the joint score (P < 0.05), serum CRP levels (P < 0.05) and the amounts of IL-1 beta produced (P < 0.01). The amounts of IL-1ra produced by unstimulated RA PBMNC did not correlate with any of the clinical parameters studied. Gold sodium thiomalate (GST), but not auranofin, increased IL-1ra production in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

The role of IL-4 and IL-6 in IL-1-dependent cartilage matrix degradation.

The objective of this paper was to study the effects of interleukin 4 (IL-4) and interleukin 6 (IL-6) on cartilage matrix degradation, the production of chondroitin-4-sulphate (C4S) and chondroitin-6-sulphate (C6S), metalloproteinase (stromelysin 1 = MMP-3) and metalloproteinase inhibitor (TIMP-1) production. Cartilage matrix degradation was assayed the release of 35SO4 from chondrocyte cultures. TIMP-1 and MMP-3 were measured by ELISA. C6S and C4S were measured by HPLC analysis. IL-1 beta significantly enhanced C4S production and significantly suppressed C6S production. Thus, the C4S/C6S ratio was significantly enhanced by IL-1 beta, and significantly suppressed by IL-4. IL-4 removed the suppressing effects of IL-1 beta for C6S and the enhancing effects of IL-1 beta for the C4S/C6S ratio. Whereas IL-1 beta stimulated the production of MMP-3, IL-4 and IL-6 had no effect on enzyme activity. IL-4, but not IL-6, removed the enhancing effects of IL-1 beta for MMP-3. In contrast, IL-4 and IL-6 significantly enhanced TIMP-1 production in chondrocytes, IL-4, but not IL-6, also significantly suppressed IL-1 beta-mediated cartilage matrix degradation. On the other hand, IL-6 significantly suppressed spontaneous cartilage matrix degradation which is supposed to be mediated by the autocrine IL-1 mechanisms. In conclusion our results suggest that IL-4 and IL-6 both protect the cartilage matrix degradation induced by IL-1.

Bone Matrix↗

Interleukin-1 receptor antagonist production in cultured synovial cells from patients with rheumatoid arthritis and osteoarthritis.

OBJECTIVE: To measure the amounts of interleukin-1 receptor antagonist (IL-1ra) protein produced by cultured synovial cells obtained from patients with rheumatoid arthritis (RA) and osteoarthritis (OA). METHODS: Synovial cells obtained from patients with either RA or OA were cultured and the supernatants were measured for IL-1ra by enzyme linked immunosorbent assay. RESULTS: The synovial cells obtained from patients with RA produced significantly smaller amounts of IL-1ra than did those obtained from patients with OA, in a late passage (third to fifth) without stimulation and a first passage both with and without stimulation (p < 0.025, respectively). In addition, when the patients with RA were divided into two groups according to the maximum number of lining cell layers, the amounts of IL-1ra produced by the proliferative type were smaller than those produced by the less proliferative type (p < 0.025). CONCLUSIONS: The above findings suggest that IL-1ra production in RA synovial cells is suppressed, and that reduced IL-1ra protein production is one of the causes which leads to the proliferation of lining cells and persistent joint inflammation.

Arthritis, Rheumatoid↗

[Clinical studies on 14 cases of adult-onset Still's disease].

We here report fourteen patients diagnosed as adult-onset Still's disease (AOSD) in our hospital. Seven patients were males (mean age at onset was 26.6 years), and seven were females (30.6 years). All of the cases had spiking fever ( > 39 degrees C) and joint symptoms. Hepatomegaly, splenomegaly, and lymphadenopathy were noted in 50% of the patients, respectively. Skin eruption was seen in twelve patients (85.7%). Among them, nine patients (64.3%) exhibited typical rash. Pleuritis or pericarditis was seen in one case each. Only one patient revealed neurological disorder. Abdominal pain was present in 50% of the cases. The ratio of occurrence of secondary amyloidosis was 14.3%. Four patients (28.6%) were diagnosed to have the apophyseal narrowing at the cervical spine (C2-C3). Two patients (14.3%) accompanied by Sjögren's syndrome were women over 40 years of age. The levels of soluble interleukin-2 receptor were significantly elevated in the sera obtained from seven patients with AOSD and four patients with juvenile-onset Still's disease, compared with normal controls. It seems to support the notion that immunopathologic processes via T cell activation play an important role in the pathogenesis of AOSD.

Adolescent↗

[Amyloidosis of the small intestine secondary to rheumatoid arthritis and juvenile rheumatoid arthritis: report of two cases].

We herein report two cases of gastrointestinal amyloidosis, secondary to juvenile rheumatoid arthritis (JRA) in one, and rheumatoid arthritis (RA) in the other. A 21-year-old woman, who has been suffering from JRA for the past 12 years, was transferred to our hospital due to intense pain in the epigastrium and back, diarrhea, high fever, and paralytic ileus. Treatment by corticosteroid, antibiotics, protease inhibitor, and total parenteral nutrition was not effective. The laparoscopic surgery was performed because of repeated melena followed by an episode of hypovolemic shock. The resected specimen of the ileum showed histologically marked amyloid deposition in the arteriolar walls. A 83-year-old man with RA for 14 years, was admitted to our hospital with complaints of abdominal pain, nausea, and diarrhea. He underwent an emergency operation for perforation of the ileum. The resected specimen revealed amyloid deposition and non-caseating granulomas. The fragility and impaired blood supply caused by amyloid deposition in the vascular walls may have terminated in the severe intestinal lesion. Further clinicopathological studies along this line are keenly desired in order to establish therapeutic modalities for gastrointestinal amyloidosis.

Adult↗

[Stromelysin-1 (MMP-3) level in the sera from patients with rheumatoid arthritis and other connective tissue diseases--clinical significances in early onset rheumatoid arthritis].

Stromelysin-1 (MMP-3) is a metalloproteinase that degrades articular cartilage matrix in patients with rheumatoid arthritis (RA). We measured MMP-3 in the sera from patients with RA and other connective tissue diseases using specific sandwich EIA and studied its clinical significance in early onset RA. MMP-3 level in healthy control (n = 170) was significantly higher in male than in female. The level of MMP-3 in RA was significantly and dramatically higher than in healthy control, osteoarthritis, systemic lupus erythematosus, progressive systemic sclerosis, primary sjogren's syndrome, mixed connective tissue disease, gouty arthritis and traumatic arthritis. Serum MMP-3 significantly correlated with serum BUN or serum creatinine levels in SLE patients but not in RA patients. In early onset RA, serum MMP-3 level was significantly elevated. Furthermore, when the relationship between the serum MMP-3 level and X-ray findings of the joints in RA was studied, it was found that MMP-3 level was elevated even in stage I or II and that there was no statistical differences between stage I or II and stage III or IV, suggesting that serum MMP-3 level is elevated in the early stage of initial inflammatory process when only mild cartilage degradation is seen. These results suggest that measurements of serum MMP-3 is an important tool for establishing diagnosis of early onset RA, and that serum MMP-3 level may be a marker of cartilage destruction and of estimating therapeutic efficacy in early onset RA.

Aged↗

Anti-inflammatory effects of recombinant human manganese superoxide dismutase on adjuvant arthritis in rats.

The anti-inflammatory effects of recombinant human manganese superoxide dismutase on adjuvant arthritis was investigated. Local application of this manganese superoxide dismutase given every 2 days not only significantly reduced foot swelling but also retarded radiological bone destruction in adjuvant arthritis. Copper zinc superoxide dismutase had little effect on foot swelling.

Animals↗

Production of soluble ICAM-1 from human endothelial cells induced by IL-1 beta and TNF-alpha.

The present study was designed to establish the effects of cytokines on soluble ICAM-1 (sICAM-1) production by human endothelial cells (EC) and ICAM-1 expression on these cells and the effects of purified sICAM-1 on lymphocyte-EC adhesion. Expression of ICAM-1 and production of sICAM-1 were measured by a specific ELISA method. ICAM-1 expression was enhanced by IL-1 beta, TNF-alpha, and most effectively by IFN-gamma. IL-4, IL-6, M-CSF, or GM-CSF showed no effects on ICAM-1 expression. IL-4 (100 units/ml) or IL-6(100 units/ml) abolished the enhancing effect of IL-1 beta, while TNF-alpha (1, 10, 100 units/ml) synergized with IL-1 beta to promote ICAM-1 expression in EC. In contrast with the transient increase of cell-associated ICAM-1 expression after activation by IL-1 beta, which peaked 40 h poststimulation and declined thereafter, sICAM-1 continued to accumulate in culture supernatants even after 48 h poststimulation in IL-1 beta-stimulated EC. IL-1 beta treatment resulted in an increase in adhesion. sICAM-1, purified from cell-free supernatants obtained after a 48-h culture of EC in IL-1 beta by affinity chromatography using monoclonal ICAM-1 antibody coupled to Sepharose beads, significantly inhibited lymphocyte EC adhesion. Preincubation of lymphocytes with conditioned medium of EC cultured with 100 units/ml IL-1 beta for 48 h, which contained a considerable amount of sICAM-1, resulted in a significant inhibition of lymphocyte adhesion to IL-1 beta-stimulated EC. These results suggest that there is a cumulative increase in sICAM-1 concentration in the vicinity of cytokine-stimulated EC and that this sICAM-1 modulates ICAM-1-mediated cell to cell interaction.

Cell Adhesion Molecules↗