Biomedical subjects

T Hidaka

Publications and source records attributed to T Hidaka.

At least 91 records · Page 5Linked to original sources

PubMed1997

Efficacy of filtration leukocytapheresis on rheumatoid arthritis with vasculitis.

The present study was designed to determine the efficacy of filtration leukocytapheresis (LCAP) in the treatment of rheumatoid arthritis (RA) with vasculitis. Nine RA patients with vasculitis were studied by the Malignant RA Collaborative Group formed by 8 clinical centers. A total of 7 filtration LCAP procedures using the Cellsorba column (Asahi Medical Co., Ltd., Tokyo, Japan) were performed with 1 week intervals between treatments. During each apheresis procedure, 3,000 ml of blood was filtered and returned to the patient at a flow rate of 50 ml/min for 60 min. In addition to the amelioration of arthritis, the improvement of extraarticular symptoms associated with rheumatoid vasculitis such as polyneuritis, skin ulcers, digital gangrene and rheumatoid nodules was obtained. In contrast, no improvement was observed in interstitial pneumonia or lung fibrosis. LCAP could be an optional modality for the treatment of RA with vasculitis.

Adult↗

PubMed1997

The mechanism of the efficiency of leukocytapheresis on rheumatoid arthritis.

This study was designed to determine the efficacy of filtration leukocytapheresis (LCAP) in the treatment of rheumatoid arthritis (RA) and the mechanism of its efficacy. Three filtration LCAP procedures in 22 RA patients were performed. Heparinized samples were collected from peripheral blood and synovial fluid. The surface markers of T cells were measured by flow cytometry before the first and third procedures. Proportions of activated and memory T cells in the peripheral blood were paradoxically higher after the third procedure than they were prior to the first treatment. Inversely, the activated T-cell counts in the synovial fluid decreased after the third procedure. In RA patients, higher proportions of activated T lymphocytes are present in RA affected joints than in the peripheral blood. If LCAP induced the redistribution of activated T cells from the affected joints into the circulating blood, the effectiveness of LCAP in the treatment of RA might be explained by the mechanism.

Arthritis, Rheumatoid↗

PubMed1997

Effects of benzoxazinorifamycin KRM-1648 on cytokine production at sites of Mycobacterium avium complex infection induced in mice.

Although various antimicrobial agents exhibit appreciable microbicidal activity in the early phase (weeks 2 t0 4) of Mycobacterium avium complex (MAC) infection induced in mice, progressive bacterial regrowth subsequently occurs. To clarify the reason for this pattern of changes, we studied changes in the levels of various cytokines in tissue at sites of infection (spleens and lungs) of MAC-infected mice which were or were not given a benzoxazinorifamycin, KRM-1648 (KRM). Levels of the proinflammatory cytokines tumor necrosis factor alpha (TNF-alpha) and gamma interferon (IFN-gamma) in tissues temporarily increased at around weeks 2 to 4 after infection, rapidly decreased thereafter, and returned to normal by week 8. Similar but somewhat delayed changes were noted for levels of interleukin 10 (IL-10) and transforming growth factor beta (TGF-beta), immunosuppressive cytokines with macrophage (M phi)-deactivating activity, in tissue, except that TGF-beta levels in the spleen remained high during weeks 4 to 8. KRM treatment blocked the increase in the levels of all of those cytokines in tissue in the early phase of infection, most strongly at week 4. IL-6 levels were beneath the limit of detection throughout the observation period. Bacterial loads in the visceral organs decreased during the first 2 weeks, and KRM treatment markedly promoted this decrease. However, regrowth of MAC organisms began at weeks 2 to 4 and continued thereafter, even in KRM-treated mice. Splenocytes and splenic M phi s of MAC-infected mice (week 2) produced and/or released into the culture fluid significant amounts of TNF-alpha (in a cell-bound form), IFN-gamma, and IL-10, but not TGF-beta, during 3 days of cultivation. A substantial amount of TGF-beta was produced during 2 weeks of cultivation of peritoneal M phi s. KRM itself did not significantly affect the IL-10- and TGF-beta-producing ability of cultured M phi s. These findings suggest that IL-10 and TGF-beta play important roles in the regrowth of MAC organisms seen during the course of KRM treatment.

Animals↗

PubMed1997

Starvation-increased insulin-dependent tyrosine phosphorylation of the 195-kDa protein in intact rat liver.

Insulin stimulates tyrosine phosphorylation of 175-195 kDa proteins including insulin receptor substrate-1 (IRS-1) in various tissues and cell types. In intact rat livers, starvation increased the insulin-dependent tyrosine phosphorylation of the insulin receptor and IRS-1 as has been described by others. Surprisingly, starvation greatly increased the tyrosine phosphorylation of the 195-kDa protein induced by insulin, indicating that this protein may be a new substrate of the insulin receptor kinase. The marked increase in tyrosine phosphorylation of the 195-kDa protein may have a physiological role in signal transmission in response to insulin under starvation conditions.

Animals↗

PubMed1997

Changes in tyrosine phosphorylation of insulin receptor and insulin receptor substrate-1 (IRS-1) and association of p85 of phosphatidylinositol 3-kinase with IRS-1 after feeding in rat liver in vivo.

The binding of insulin to its receptor rapidly induces intrinsic insulin receptor tyrosine kinase activity, resulting in tyrosine phosphorylation of various cytosolic substrates, such as insulin receptor substrate-1 (IRS-1) which, in turn, associates with a p85 subunit of phosphatidylinositol 3-kinase (PI 3-kinase) followed by activation of this enzyme. In the present study, we have examined these early steps of insulin signalling in rat liver in vivo after food ingestion. After fasting for 22 h, a 12% casein diet was available ad libitum throughout the 8-h experimental period. Plasma insulin concentrations increased within 45 min after feeding, reached a maximum at 1.5 h and gradually decreased until 8 h. Autophosphorylation of the insulin receptor beta-subunit in liver was detected even during fasting and increased about 1.5-fold at 1.5 h after feeding. Basal tyrosine phosphorylation of IRS-1 was detectable during starvation, increased about twofold at 3 h after feeding and levels were maintained until 8 h. The content of the p85 subunit of PI 3-kinase associated with IRS-1 also increased after feeding in parallel with the changes in tyrosine phosphorylation of IRS-1. Because tyrosine phosphorylation of the insulin receptor beta-subunit and IRS-1 and the association of the p85 subunit of PI 3-kinase with IRS-1 in liver were closely correlated with the changes in the plasma concentration of insulin, we concluded that endogenous insulin secreted in response to eating caused these insulin-dependent intracellular changes in the liver.

Animals↗

PubMed1997

Rapidly progressive interstitial lung disease associated with dermatomyositis responding to intravenous cyclophosphamide pulse therapy.

Interstitial lung disease, especially the rapidly progressive type, carries a grave prognosis when associated with polymyositis (PM)/dermatomyositis (DM). We describe a case of rapidly progressive interstitial lung disease associated with DM. Pathological findings included bronchiolitis obliterans organizing pneumonia (BOOP) pattern in the right upper lung lobe and interstitial fibrosis with microscopic honeycomb lesions in the right lower lung lobe. The patient's respiratory distress was severe and persistent, and oral intubation with mechanical ventilation was transitionally introduced. The respiratory distress condition responded to intravenous cyclophosphamide pulse therapy.

Autoimmune Diseases↗

PubMed1997

SLE and Sjögren's syndrome associated with unilateral moyamoya vessels in cerebral arteries.

Moyamoya disease is a rare clinical entity, diagnosed by cerebral angiography and characterized by occlusion of the internal carotid artery system and the development of collateral arteries. A 30-year-old woman with systemic lupus erythematosus and Sjögren's syndrome recurrently presented transient right homonymous hemianopsia. Cerebral angiography showed occlusion of the left posterior cerebral artery associated with the development of collateral circulation ("moyamoya vessels"). In a young adult, as in this case, the unilaterality of the lesion and the presentation of transient ischemic attacks rather than subarachnoid hemorrhage are rare features for Moyamoya disease. Antiphospholipid syndrome was absent.

Adult↗

PubMed1997

Primary Sjögren's syndrome associated with hyaline-vascular type of Castleman's disease and autoimmune idiopathic thrombocytopenia.

We describe a case of primary Sjögren's syndrome complicated by hyaline-vascular type of Castleman's disease and autoimmune idiopathic thrombocytopenia. This type of Castleman's disease was diagnosed by biopsy of a right axillary lymph node 7 years after the onset of Sjögren's syndrome. The specimen showed small hyaline-vascular lymphoid follicles and interfollicular capillary proliferation. Serum IL-6 was slightly increased, but systemic manifestations, such as fever or weight loss, were not present. Hyaline-vascular type of Castleman's disease should be considered a lymphoproliferative disorder associated with Sjögren's syndrome.

Biopsy↗

PubMed1997

[Scanning and transmission electron microscopic observations of the inner ear of hamsters with hyperlipidemia].

The relationship between hyperlipoproteinemia and sensorineural hearing loss has been studied by means of guinea pig models with hypercholesterolemia. However, these observations of the inner ear using guinea pig models have been limited to a short time. By using a golden hamster model with hypercholes terolemia, I was able to observe the inner ear for a long time. Two-month-old hamsters were fed a hyperlipid diet consisting of standard chow supplemented with 3% cholesterol and 15% cattle fat for 30, 60, 90, 120, and over 150 days. Six-month-old hamsters were fed the hyperlipid diet for 30 days. Then the animals were examined for auditory dysfunction and morphological changes in the cochlea. Biochemical findings in the serum showed hyperlipoproteinemia, especially hypercholesterolemia. Regarding auditory dysfunction, the threshold change in the auditory brainstem response (ABR) was mild. Scanning and transmission electron microscopic revealed many protrusions toward the endolymphatic space on the surface of the marginal cells of the stria vascularis. Vascular degeneration of the marginal cells and intermediate cells of the stria vascularis was also observed. In addition, protrusions containing a lysozome structure consisting of outer piller cells were observed on the organ of Corti. These results with experimental hamsters fed a hyperlipid diet indicate that such a diet may induce functional changes in the cochlea such as auditory dysfunction with the occurrence in hypercholesterolemia.

Animals↗

PubMed1997

[Radiographic and pathological findings in 4 patients with pulmonary cryptococcosis].

We reviewed the records of 4 patients with pathologically diagnosed pulmonary cryptococcosis to determine whether there was any relationship between radiographic and pathological findings. The underlying disease were diabetes mellitus (patient 1), rheumatoid arthritis treated with glucocorticoids (patient 2), and adultonset T cell leukemia (patients 3 and 4). All radiographs showed multiple nodules, and patchy and localized infiltrates, which progressed to diffuse interstitial infiltration. According to Mark's classification, the pathological findings in patients 1 and 2 showed granulomatous pneumonia, those in patient 3 showed histiocytic pneumonia, and patient 4 had intercapillary cryptococci with no inflammatory response. The granuloma appeared larger in patient 1 than in patient 2. This concurred with the clinical findings, i.e. large granulomas formed in immunocompetent patients, and diffuse pulmonary infiltrates developed in those whose immune systems had been compromised. When a granuloma formed, roentgenograms showed a well defined nodular shadow, with some nodules developing in the cavity. When granuloma formation became unclear, roentgenograms tended to show localized-to-diffuse infiltration, or interstitial shadows.

Cryptococcosis↗

PubMed1997

Studies on the biosynthesis of bialaphos. Biochemical mechanism of C-P bond formation: discovery of phosphonopyruvate decarboxylase which catalyzes the formation of phosphonoacetaldehyde from phosphonopyruvate.

The biosynthetic step following the phosphoenolpyruvate (PEP) phosphomutase reaction which forms a C-P bond of bialaphos was proven by the identification of phosphonopyruvate (PnPy) and phosphonoacetaldehyde (PnAA) as intermediates in the culture broth of Streptomyces hygroscopicus, a producing organism of bialaphos, and by detection of enzymatic decarboxylation of PnPy to PnAA. Purified PnPy decarboxylase turned out to require thiamine diphosphate and Mg2+ as cofactors. PnPy decarboxylase drives the unfavorable forward reaction to form PnPy catalyzed by PEP phosphomutase and is suggested to be essential to C-P compound biosynthesis.

Acetaldehyde↗

PubMed1997

[Evaluation of a new anti-cancer drug regimen against uterine cervical cancer in nude mice].

The purpose of this study was to describe a new anti-cancer drug regimen for uterine cervical cancer. The cytotoxicities of some anti-cancer drugs regimens against the human uterine cervical cancer xenografted into nude mice have been studied. The activities of CDDP, CPT-11, TXL, CDDP + BLM, CDDP + MMC, CPT-11 + BLM, CPT-11 + CDDP, CDDP + 5-FU, CPT-11 + MMC, CPT-11 + TXL and CDDP + TXL for squamous cell carcinoma (TCR, TCK, TCG), and CDDP, MMC, TXL, CDDP + TXL, CDDP + MMC and MMC + TXL for adenocarcinoma (TCO, TCM, TCY), were evaluated comparing with a control group using saline. Five mice were used for each groups. When the xenografted tumor reached 6 mm in diameter, 1/5 LD50 of these drugs were administered into the peritoneal cavity of the mice once a week for three weeks. The effective regimens were CDDP + MMC, CDDP + BLM, CDDP + CPT-11 and CPT-11 + MMC for squamous cell carcinoma of the uterine cervix. CDDP + MMC, CDDP + TXL, MMC + TXL and CDDP were effective for endocervical adenocarcinoma. It was suggested that these new drug regimens should be used in clinical studies.

Adenocarcinoma↗

PubMed1997

Characterization of a newly established human tumor cell line (TEN) from a patient with clear cell carcinoma of the uterine body and its sensitivity to anti-cancer agents.

A cell line derived from human endometrial clear cell adenocarcinoma was newly established and named TEN. The tumor cells were obtained from uterine body of a 74-year-old who had been undergone an abdominal simple hysterectomy. The histologic features of the tumor cells showed abundant clear cytoplasm with diastase digested glycogen granule growing in solid nest and tubular pattern. The TEN cells were continuously propagated in vitro during the past 45 months and they were at 75th passage. They grew in a monolayered sheet with a doubling time of about 53 hours. The TEN cells resembled the structure of the original tumor and had abundant glycogen granules, lipid droplets in the cytoplasm. The histopathology of the transplanted tumor in SCID mice resembled that of the original tumors. The TEN cells secreted a high content of CA125. Immunohistochemically, the TEN cells had c-erbB-2 and Cathepsin D immunoreactivity in some parts of the cell population. But they did not have estrogen, progesterone and EGF receptor. Sensitivities of the TEN cells to a variety of anti-cancer drugs were examined. In in-vitro tests, MTT assays employed. The results suggested that the TEN cells were not sensitive to any of 13 agents. On the other hand, in-vivo sensitivity test of transplanted tumor in SCID mice, the tumors were sensitive to CPT-11 and paclitaxel. We conclude that the TEN cell line will be effective material for chemosensitivities against the endometrial clear cell adenocarcinoma.

Adenocarcinoma, Clear Cell↗

PubMed1997

Studies on the biosynthesis of bialaphos. Biochemical mechanism of C-P bond formation: discovery of phosphonopyruvate decarboxylase which catalyzes the formation of phosphonoacetaldehyde from phosphonopyruvate

Journal Article↗

PubMed1996

Thromboxane A2 receptor blockade suppresses intercellular adhesion molecule-1 expression by stimulated vascular endothelial cells.

Inhibition of the thromboxane A2-synthesizing enzyme (DP-1904: [+/-]-6-[1-imidazolylmethyl]-5,6,7,8-tetrahydronaphthalene-2-carbo xylic acid hydrochloride hemihydrate) reportedly suppresses intercellular adhesion molecule-1 (ICAM-1) expression on the surface of stimulated vascular endothelial cells (Ishizuka et al., 1994, Eur. J. Pharmacol 262, 113). In the present study, thromboxane A2 receptor antagonists suppressed the expression of ICAM-1 on the surface of human vascular endothelial cells that were stimulated by tumor necrosis factor alpha (TNF alpha), platelet activating factor (PAF), or U46619 (9,11-dideoxy-9 alpha, 11 alpha-epoxymethanoprostaglandin F2 alpha). Augmentation of ICAM-1 expression on human vascular endothelial cells stimulated by U46619 was suppressed by protein kinase C inhibitors. Thromboxane A2 receptor antagonist suppressed U46619 stimulation of protein kinase C activity of a cell membrane fraction. These results indicate that in human vascular endothelial cells, thromboxane A2, the production and secretion of which is stimulated by TNF alpha or PAF, binds to the thromboxane A2 receptors on cell membranes and augments ICAM-1 expression on the cell surfaces mainly through protein kinase C.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

PubMed1996

Anti-DNA antibody kinetics following selective removal by adsorption using dextran sulphate cellulose columns in patients with systemic lupus erythematosus.

The aim of this study is to determine by mathematical analysis which of two models, the one- or the two-compartment model, more closely approximates the kinetics of anti-dsDNA following immunoadsorption procedures in patients with systemic lupus erythematosus. Titers of anti-dsDNA were measured at specified intervals after apheresis to each model by nonlinear least-squares methods, and Akaike's Information Criterion (AIC) was calculated to determine which model most approximately described the kinetics. The AIC of the two-compartment model was larger than that of the one-compartment model in all 14 SLE patients (P < .001). Therefore, the one-compartment model is thought to be suitable. The generation rate and catabolic rate of anti-dsDNA were obtainable using this model. The anti-dsDNA replenishment curve after an immunoadsorption session was defined by only two parameters: the generation and catabolic rates of anti-dsDNA.

Adolescent↗

PubMed1996

High-avidity anti-DNA antibody removal from the serum of systemic lupus erythematosus patients by adsorption using dextran sulfate cellulose columns.

The purpose of this study is to determine whether immunoadsorption treatment using a dextran sulfate (DS) column can remove high-avidity anti-double-stranded DNA (anti-dsDNA) antibody from the blood of patients with systemic lupus erythematosus (SLE). Before and after each immunoadsorption therapy routine, titers of the high-avidity anti-dsDNA antibody of 11 SLE patients were measured by using a newly developed assay kit to exclusively detect high avidity anti-DNA antibody. Patients with active SLE showed significantly higher titers of high-avidity antibody than did those with inactive SLE, and their titers were significantly reduced by immunoadsorption procedures. Removal of high-avidity antibodies in vitro was also confirmed by mixing patients' sera and DS gel. Immunoadsorption therapy using DS columns is effective in the removal of high-avidity anti-dsDNA antibodies that are closely associated with pathogenicity in SLE.

Adult↗

PubMed1996

Anti-dsDNA antibody kinetics during in vivo apheresis in systemic lupus erythematosus patients and in an in vitro apheresis model.

Levels of anti-dsDNA measured just after an immunoadsorption procedure in systemic lupus erythematosus (SLE) patients are sometimes paradoxically larger than those measured just before the procedure. A 1:100 in vitro single-compartment immunoadsorption system model was devised to determine which of two models, one- or two-compartment, more closely approximates the kinetics of anti-dsDNA during apheresis procedures. Ten SLE patients were employed in this study. A total of 4,100 ml of plasma was passed through the dextran sulfate cellulose columns during one clinical apheresis session. In eight of ten patients, the log of RIA-measured anti-dsDNA titers decreased linearly as treated plasma volume increased, in both the clinical procedure and the experimental model. The mean adsorption efficacy in the clinical apheresis procedure and in the in vitro model was 0.37 and 0.27, respectively. However, in one patient the RIA-measured level of anti-dsDNA increased during the apheresis procedure; this phenomenon was mirrored in the model (definitely a single pool model). In contrast, the level of anti-dsDNA, as measured by ELISA, decreased in accordance with the increase of treated plasma volume in both the clinical and the in vitro apheresis procedures. Therefore, an increased titer of anti-dsDNA as measured by RIA immediately following clinical apheresis cannot be accounted for exclusively by an inflow of antibodies from a secondary (extravascular) pool into the circulating plasma. In short, a one-compartment model is applicable and an explanation must be sought elsewhere.

Adult↗