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T Hidaka

Publications and source records attributed to T Hidaka.

At least 163 records · Page 9Linked to original sources
PubMed1992

Presence of autoantibodies to peptidyl-prolyl cis-trans isomerase (cyclosporin A-binding protein) in systemic lupus erythematosus.

Several autoantibodies against cytoplasmic or nuclear components of cells have been reported in autoimmune diseases. We report here a previously unrecognized autoantibody to peptidyl-prolyl cis-trans isomerase (PPIase) in patients with systemic lupus erythematosus (SLE). PPIase, which catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides, has recently been found to be identical to cyclophilin, a specific binding protein of a potent immunosuppressant, cyclosporin A. IgG and IgM anti-PPIase antibodies were detected in 40 and 20% of unselected patients with SLE, respectively, by ELISA. The reactivity of these sera was confirmed by immunoblotting experiments. Sera from rheumatoid arthritis patients showed no reactivity and 1 of 8 sera from systemic sclerosis patients and 1 of 25 sera from normal controls showed only weak reactivity. Unexpectedly, the anti-PPIase antibody was unable to inhibit PPIase activity, indicating that the autoantibody recognizes an epitope of PPIase which is different from the active site of PPIase. The levels of the anti-PPIase antibody in SLE patients correlated with remissions and flares of the disease. The anti-PPIase antibody was higher in patients with active SLE than those with inactive disease. The prevalence of the active stage of the disease was significantly higher in IgG anti-PPIase antibody-positive SLE patients as compared to antibody-negative SLE patients. These data define the presence of a new autoantibody against PPIase and its association with the activity and certain clinical manifestations in SLE.

Adult↗
PubMed1992

In vitro and in vivo activities of KRM-1648, a newly synthesized benzoxazinorifamycin, against Mycobacterium marinum.

The in vitro and in vivo activities of KRM-1648, one of the newly synthesized benzoxazinorifamycins, against M. marinum were compared with those of rifampin. The MIC values of KRM-1648 determined by the agar dilution method on 7H11 medium against 10 strains of M. marinum were 32-128 times and even more below those of rifampin. In an in vivo experiment, KRM-1648 was markedly effective in terms of the incidence of gross skin lesions and the number of CFUs in the lungs and spleen. Its efficacy was much greater than that of rifampin.

Animals↗
PubMed1992

Autostimulatory effects of IL-6 on excessive B cell differentiation in patients with systemic lupus erythematosus: analysis of IL-6 production and IL-6R expression.

Introducing avidin-biotin complex ELISA for anti-DNA antibody, the mechanism of in vitro production of anti-ssDNA antibody as well as of polyclonal immunoglobulin mediated by an IL-6-IL-6R loop was studied in patients with systemic lupus erythematosus (SLE). Regardless of the presence or absence of T cells, B cells from SLE patients could produce IgG anti-ssDNA antibody as well as total IgG without any stimulation. Low density B cells obtained by Percoll gradient density centrifugation responded to rIL-6 to produce IgG and IgG anti-ssDNA antibody. rIL-2 and rIL-4 had lesser effects on the differentiation of low density B cells. In fact, IL-6R was preferentially expressed on low density B cells from active SLE patients, as detected by anti-IL-6R MoAb, MT18, which did not inhibit IL-6 binding. SLE B cells, especially high density B cells, produced greater amounts of IL-6 in culture supernatants than did T cells, regardless of whether disease was active or inactive. Normal T cells and B cells did not produce significant amounts of IL-6. Thus, endogenous IL-6 produced by high density B cells bound to the IL-6R preferentially expressed on the low density B cells, and drove them into terminal differentiation, especially in active SLE patients. Further, addition of polyclonal anti-IL-6 or anti-IL-6R MoAb (PM1), which inhibited IL-6 binding, both inhibited IgG anti-ssDNA antibody as well as total IgG production by SLE B cells in a dose-dependent manner. These results suggest that interruption of the autocrine IL-6 loop would be of therapeutic value in SLE.

Antibodies, Antinuclear↗
PubMed1992

IL-4 down-regulates the surface expression of CD5 on B cells and inhibits spontaneous immunoglobulin and IgM-rheumatoid factor production in patients with rheumatoid arthritis.

There is evidence to suggest that CD5+ B cells may be associated with autoimmunity, e.g. they are increased in patients with rheumatoid arthritis (RA). In this study, we found that the expression of CD5 on RA B cells increased spontaneously, following culture for up to 4 days in vitro in the absence of T cells, supporting the idea that the CD5+ B cell possesses distinctive features. The spontaneous increase of CD5 expression was down-regulated by recombinant IL-4 (rIL-4). Other cytokines studied (rIL-1 alpha, rIL-2, rIL-5, rIL-6) did not alter CD5 expression. Studies of antibody production showed that rIL-4 could reduce spontaneous production of total IgG and IgM in non-stimulated RA T plus B cell cultures. Spontaneous production of IgM rheumatoid factor (IgM-RF), measured by a newly developed avidin-biotin complex ELISA, was also reduced by rIL-4. Furthermore, rIL-4 reduced the increase in IgM-RF production observed on stimulation with Staphylococcus aureus Cowan I (SAC) or pokeweed mitogen (PWM). Thus, IL-4 might act as a regulator of the development of abnormal B cell differentiation in patients with RA.

Adult↗
PubMed1992

Chemotherapeutic efficacy of a newly synthesized benzoxazinorifamycin, KRM-1648, against Mycobacterium avium complex infection induced in mice.

Newly synthesized benzoxazinorifamycin, KRM-1648, was studied for its in vivo anti-Mycobacterium avium complex (MAC) activities. When the MICs were determined by the agar dilution method with Middlebrook 7H11 agar medium, KRM-1648 exhibited similarly potent in vitro antimicrobial activities against the MAC isolated from AIDS and non-AIDS patients, indicating possible usefulness of KRM-1648 against AIDS-associated MAC infections. KRM-1648 exhibited potent therapeutic activity against experimental murine infections induced by M. intracellulare N-260 (virulent strain) and N-478, which has much weaker virulence. Similarly, KRM-1648 exhibited an excellent therapeutic efficacy against M. intracellulare infection induced in NK-cell-deficient beige mice (as a plausible model for AIDS-associated MAC infection), in which a much more progressed state of gross lesions and bacterial loads at the sites of infection were observed. When the infected beige mice were killed at weeks 4 and 8, obvious therapeutic efficacy was seen on the basis of reduction in the incidence and degree of lung lesions and bacterial loads in the lungs and spleen with infections due to M. intracellulare N-241, N-256, and N-260. In this case, the efficacy was the highest in N-260 infection, followed by strain N-241. When mice were observed until infection-induced death, survival time of the infected beige mice was found to be prolonged by KRM treatment. However, KRM-1648 was not efficacious in suppressing the progression of pulmonary lesions and the increase in bacterial loads at the sites of infection, including lungs and spleen, at the late phase of infection. This may imply some difficulty with chemotherapy for AIDS-associated MAC infection, even with KRM-1648 treatment, which has excellent in vitro and in vivo anti-MAC activities, as shown in present study.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Purification and characterization of phosphoenolpyruvate phosphomutase from Pseudomonas gladioli B-1.

Phosphoenolpyruvate phosphomutase (PEPPM) catalyzes C-P bond formation by intramolecular rearrangement of phosphoenolpyruvate to phosphonopyruvate (PnPy). We purified PEPPM from a gram-negative bacterium, Pseudomonas gladioli B-1 isolated as a C-P compound producer. The equilibrium of this reaction favors the formation of the phosphate ester by cleaving the C-P bond of PnPy, but the C-P bond-forming reaction is physiologically significant. The C-P bond-forming activity of PEPPM was confirmed with a purified protein. The molecular mass of the native enzyme was estimated to be 263 and 220 kDa by gel filtration and polyacrylamide gel electrophoresis, respectively. A subunit molecular mass of 61 kDa was determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, indicating that the native protein was a tetramer. The optimum pH and temperature were 7.5 to 8.0 and 40 degrees C, respectively. The Km value for PnPy was 19 +/- 3.5 microM, and the maximum initial velocity of the conversion of PnPy to phosphoenolpyruvate was 200 microM/s/mg. PEPPM was activated by the presence of the divalent metal ion, and the Km values were 3.5 +/- 1.4 microM for Mg2+, 16 +/- 5 nM for Mn2+, 3.0 +/- 1.5 microM for Zn2+, and 1.2 +/- 0.2 microM for Co2+.

Carbon↗
PubMed1992

Synthesis and biological activity of 5'-aminobenzoxazinorifamycin derivatives.

Benzoxazinorifamycin reacted with various secondary amines to yield various 5'-substituted aminobenzoxazinorifamycin derivatives. The derivatives exhibited potent activities against gram-positive bacteria and mycobacteria. The antimicrobial activities of these compounds against Mycobacterium tuberculosis and Mycobacterium intracellulare were superior to those of rifampicin. Some of these compounds showed good plasma levels after oral administration in rats.

Animals↗
PubMed1992

Effects of nitric oxide-related compounds and carperitide on hemodynamics and hematocrit in anesthetized rats.

Sodium nitroprusside, nitroglycerin and carperitide (alpha-human ANP) all reduced mean blood pressure, but only carperitide increased the hematocrit in rats with bilateral renal artery- and ureter-ligation. NG-Monomethyl-L-arginine, a selective inhibitor of nitric oxide synthesis, elevated the mean blood pressure but did not change the hematocrit significantly. These findings suggest that ANP has a physiological role in regulating circulatory blood volume distinct from that of NO, although both increase intracellular cyclic GMP in the vasculature.

Anesthesia↗
PubMed1992

Fluorescent probe-labeled lipid microsphere uptake by human endothelial cells: a flow cytometric study.

Lipid microspheres have been used as carriers of drugs such as prostaglandin E1 (lipo-PGE1) and corticosteroid (liposteroid). Lipo-PGE1 is used for the treatment of chronic arterial occlusive diseases because its activity is far greater than that of free PGE1 in vivo. To verify the fact that the drug carriers, lipid microspheres, are preferentially taken up by endothelial cells, we labeled lipid microspheres with a fluorescent probe, DiI (DiI-LM), and observed them in some in vitro models. Stoichiometric fluorescence was obtainable, and the fluorescence was stable between pH 3.3 and pH 8.9. Human umbilical vein endothelial cells and cells of a human endothelial cell line, ECV304, showed increased uptake of DiI-LM, 81% and 61%, respectively. In contrast, uptakes were less than 7% in human skin fibroblasts, 3T3 cells, and human neutrophils. Prominent perinuclear fluorescence was also observed in endothelial cells by fluorescence microscopy. DiI-LM and flow cytometric analysis will be useful for studies to elucidate the precise mechanism of the selective accumulation of lipid microspheres by cells in blood vessel walls.

Carbocyanines↗
PubMed1992

Malignant lymphoma in the mesentery with immune thrombocytopenia.

A 69-year-old man was referred to our hospital for further evaluation of an abdominal mass. After admission, he was suspected of having a malignant mesenteric tumor. Laboratory data disclosed thrombocytopenia with increased levels of platelet-associated immunoglobulin G. On surgery, the tumor involved the ileal mesentery, invading the urinary bladder and mucosal surface of the terminal ileum. The diagnosis of mesenteric lymphoma with immune thrombocytopenia was made. Complete remission was obtained after surgery and the subsequent three courses of combination chemotherapy. However, thrombocytopenia still persisted. This rare presentation is discussed with a review of the available literature.

Aged↗
PubMed1992

Identification of free and esterified hydroxyoctadecadienoates (HODEs) and linoleate-hydroxylating pathway in the epidermis of hairless mice.

Epidermal homogenates of hairless mice contained a large amount of lipid material showing a single peak on reverse phase (RP)-high pressure liquid chromatography (HPLC) with a maximum absorbance of 234 nm, which was different in retention time from arachidonate metabolites such as 12-HETE, 15-HETE and 5-HETE. The production of this material was dependent on exogenous linoleate concentration, protein concentration and buffer pH. This material was identified to be a mixture of 13-HODE and 9-HODE on the basis of UV absorbance spectra, retention times on RP-HPLC, straight phase (SP)-HPLC, gas chromatography-mass spectrometry (GC/MS) and mass spectra obtained. As assessed by SP-HPLC after saponification, these two HODEs were found to exist primarily in esterified forms in the skin. Neither substance was produced following heat denaturation of the homogenate. These results indicate that 13- and 9-HODEs are produced from linoleate enzymatically at physiologically relevant levels in the epidermis of hairless mice. Thus, it is possible that these two materials may play some important role in pathophysiology of the skin.

Animals↗
PubMed1992

Studies on the biosynthesis of bialaphos (SF-1293) 12. C-P bond formation mechanism of bialaphos: discovery of a P-methylation enzyme.

An enzymatic activity catalyzing P-methylation of N-acetyldemethylphosphinothricin, a biosynthetic intermediate of the herbicide bialaphos, was detected in a cell extract of Streptomyces hygroscopicus SF-1293, a bialaphos producing organism. The gene coding for this P-methylation enzyme in the bialaphos biosynthetic gene cluster was also expressed in Streptomyces lividans. The methyl donor of the reaction was determined to be methylcobalamin. The P-methylation enzyme utilized both N-acetyldemethylbialaphos and N-acetyldemethylphosphinothricin as substrates.

Herbicides↗
PubMed1992

Rapid growth and difficulty of early detection of scirrhous carcinoma of the stomach.

We report six cases of scirrhous carcinoma of the stomach in which we were able to observe the natural history of serial radiographs. All the patients developed scirrhous carcinoma of the stomach in an observation periods ranging from 2 to 15 months (mean: 5.8 months). No abnormalities or obvious findings indicative of a carcinoma were detectable, on the prior radiographs, even when they were reviewed. Endoscopy was also performed in two patients during the observation period, and no lesions were detected. At the time of diagnosis, two patients were inoperable because of metastases and died of the disease 2 and 5 months later. Three patients died of the disease 5, 8, and 26 months after gastrectomy, respectively. Only one patient is free of disease 16 months after gastrectomy. Our findings suggest that the difficulty of detection and the rapid growth of this tumor may explain why it is seldom detected at an early stage and has a very poor prognosis.

Adenocarcinoma, Scirrhous↗
PubMed1992

Cytokine regulation of prolyl 4-hydroxylase production in skin fibroblast cultures from patients with systemic sclerosis: contribution to collagen synthesis and fibrosis.

Prolyl 4-hydroxylase (PH) is an enzyme that catalyzes an essential step in procollagen synthesis. PH production, as measured by the new ELISA method, was significantly higher in fibroblast cultures from patients with systemic sclerosis (SSc; N = 7) than in cultures from healthy controls (NC; N = 5) (p less than 0.01). Transforming growth factor-beta and tumor necrosis factor-alpha significantly increased PH production, but recombinant interferon-gamma had a significant negative effect on PH production. Since the production of PH is relevant to collagen synthesis by fibroblasts of patients with SSc, regulation of PH production may have therapeutic value.

Cells, Cultured↗
PubMed1992

Effect of prolyl 4-hydroxylase inhibitor on fibroblast collagen production in vitro: an approach to the treatment of systemic sclerosis.

Prolyl 4-hydroxylase (PH), which catalyzes the conversion of prolyl residues to 4-hydroxyproline, plays a central role in the synthesis and secretion of collagen. We demonstrated that fibroblasts from patients with systemic sclerosis produced significantly more PH than those from healthy subjects. To regulate excessive collagen production by scleroderma fibroblasts, we examined the effect of a PH inhibitor on collagen production by scleroderma fibroblasts. Fibrostatin-C, a PH inhibitor, significantly decreased the amount of procollagen (type I) production by scleroderma fibroblasts (p < 0.01). We suggest that this PH inhibitor might be a valid antifibrotic agent useful for the treatment of patients with scleroderma.

Blotting, Northern↗