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Biomedical subjects

Y Hidaka

Publications and source records attributed to Y Hidaka.

At least 145 records · Page 8Linked to original sources
PubMed1992

Inhibition of cultured vascular smooth muscle cell migration by simvastatin (MK-733).

The effect of simvastatin (MK-733), a potent 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, on the migration of cultured porcine smooth muscle cells (SMCs) was investigated in modified Boyden chambers. Platelet-derived growth factor (PDGF) stimulated the SMC migration dose dependently. MK-733 inhibited the migration response induced by PDGF with an IC50 value of 2 microM. Supplementation with mevalonate restored the migration response inhibited by MK-733 but the addition of low-density-lipoprotein (LDL) did not change the response. Another HMG-CoA reductase inhibitor, pravastatin (CS-514), also reduced the migration response. However its potency was far less than that of MK-733. MK-733 also inhibited the SMC migration stimulated by fibrinogen. These results suggest that non-sterol metabolite(s) of mevalonate, possibly prenylated proteins, are involved in a migration signaling pathway and that HMG-CoA reductase inhibitors are effective in the prevention of the formation of intimal hyperplasia in atherosclerosis.

Animals↗
PubMed1992

Serum interleukin 6 levels become elevated in acute myocardial infarction.

We have examined serum interleukin 6 (IL-6) levels in 12 patients with acute myocardial infarction (AMI). IL-6 levels became elevated in all patients, following the rise of serum creatine kinase (CK) activity. Peak IL-6 levels showed a good correlation with peak serum C-reactive protein (CRP) levels, while there was no direct relationship between peak IL-6 levels and peak CK activity. IL-6 mRNA was not detected in unstimulated "quiescent" rat cardiocytes cultured in serum-free medium, but its expression was induced by exposure of the cells to serum or ionomycin. These results show that IL-6 is synthesized in the myocardium and serum IL-6 levels become elevated in AMI, suggesting that IL-6 could affect the progression and/or healing processes of AMI.

Aged↗
PubMed1992

Consumption of milk from cows immunized with intestinal bacteria influences age-related changes in immune competence in mice.

Milk was obtained from nonimmunized cows and cows immunized with a mixture of various human gut bacteria. Each milk was administered orally to 2-mo-old C57BL/6 mice at a dose of 150 g.kg-1.d-1 for either 6 or 16 mo. The study group had fewer enteric bacteria and a lower concentration of the serum antibodies against enteric bacteria compared with the control group at 8 and 18 mo of age. Furthermore, the study group at 18 mo old had a higher redirected cytotoxicity of intestinal intraepithelial lymphocytes, a higher proliferative response of mesenteric lymph nodes cells against mitogenic or alloantigenic stimulation and a greater ability of the spleen cells to produce anti-sheep erythrocytes IgG antibody after systemic immunization with sheep erythrocytes. A lower level of autoantibodies was observed at 8 mo and 18 mo of age in the study group compared with the control group. These results suggest that the senescence of the murine immune system may be delayed by consumption of milk from immunized cows.

Animals↗
PubMed1992

Decreases in alpha beta T cell receptor negative T cells and CD8 cells, and an increase in CD4+ CD8+ cells in active Hashimoto's disease and subacute thyroiditis.

We examined peripheral lymphocyte subsets in patients with autoimmune thyroid disease, or subacute thyroiditis, in the active stage when possible. During destructive thyrotoxicosis arising from alpha beta T cell receptor (TCR) negative T (WT31-CD3+) cells and CD8 (CD4-CD8+) cells decreased and those of CD4+CD8+ cells increased slightly, resulting in proportional increases in CD4 (CD4+CD8-) cells, non-T, non-B (CD5-CD19-) cells, and the CD4/CD8 cell ratio. Changes were similar in active subacute thyroiditis. During stimulative thyrotoxicosis in active Graves' disease, the numbers of such T lymphocyte subsets were not changed, but only the number of CD5+ B (CD5+CD19+) cells increased markedly, resulting in proportional decreases in total T (CD3+) cells, alpha beta+ TCR T (WT31+CD3+) cells, CD8 cells, and non-T, non-B cells. A serial study of some of the patients showed opposite changes in alpha beta TCR- T cells, the CD4/CD8 cell ratio, and CD5+ B cells between the active stages of Graves' and Hashimoto's diseases. alpha beta TCR- T cells were mostly gamma delta TCR+ T (IIF2+ CD3+) cells in these patients. These data suggest that alpha beta TCR-T (gamma delta TCR+ T), CD8, and CD4+ CD8+ cells are important in thyroid destruction in Hashimoto's disease and subacute thyroiditis, and that CD5+ B cells are important in thyroid stimulation in Graves' disease.

Adult↗
PubMed1992

Effect of an inhibitor of squalene epoxidase, NB-598, on lipid metabolism in Hep G2 cells.

NB-598, a potent inhibitor of squalene epoxidase, inhibited cholesterol synthesis from [14C]acetate and induced intracellular squalene accumulation in Hep G2 cells. NB-598 inhibited cholesterol synthesis from [14C]acetate, [3H]mevalonate, and [3H]squalene, but not from [3H]2,3-oxidosqualene in Hep G2 cells. It reduced cholesterol ester synthesis remarkably in the absence of exogenous cholesterol. This compound did not have any effect on the synthesis of ubiquinone and dolichol. When Hep G2 cells were prelabeled with micellar [3H]cholesterol, NB-598 did not affect the excretion of bile acid incorporated from [3H]cholesterol. However, NB-598 decreased the secretion of free and esterified cholesterol, triacylglycerol, and phospholipids, and increased the secretion of squalene. NB-598 is thought not only to inhibit cholesterol synthesis, but also to inhibit the secretion of lipids.

Anticholesteremic Agents↗
PubMed1992

Increase in peripheral natural killer cell activity in patients with autoimmune thyroid disease.

Changes in the activity and number of natural killer (NK) cells in peripheral blood in patients with autoimmune thyroid disease were examined. NK activity was measured in a 4-hr 51Cr-release assay and the number of NK cells was analyzed with FITC-conjugated monoclonal antibodies by use of an automated flow cytometer. NK activity in patients with untreated Graves' disease (n = 25, 39.7 +/- 13.5%, P less than 0.05) and Hashimoto's thyroiditis (n = 18, 41.0 +/- 14.2%, P less than 0.05) was high compared to the activity in non-pregnant controls (n = 61, 32.6 +/- 15.0%). NK activity in patients with postpartum Graves' thyrotoxicosis (n = 11, 48.6 +/- 18.9%) was markedly increased compared to the activity in non-pregnant controls (P less than 0.01) and in postpartum controls (n = 29, 33.8 +/- 15.2%, P less than 0.05), although the mean ages of each group did not differ significantly. Moreover, NK activities in the thyrotoxic state were significantly higher than those in the euthyroid state in the same patients with postpartum Graves' thyrotoxicosis or with postpartum destructive thyrotoxicosis. The number of CD16 positive cells increased in patients with postpartum Graves' thyrotoxicosis. However the number of CD16 and CD57 positive cells were normal in all other groups of patients. These results indicate that an increase of NK activity is associated with exacerbation of autoimmune thyroid disease both in Hashimoto's thyroiditis and in Graves' disease and suggest that NK cells might have an important role for the control of disease activity in autoimmune thyroid disease.

Adult↗
PubMed1992

[Analysis of circulating thyroid-stimulating activities in pregnant women with Graves' disease: differential measurement of activities induced by TSH receptor antibody and hCG].

Thyrotoxicosis in Graves' disease is often aggravated in early pregnancy and this aggravation is associated with postpartum relapse of thyrotoxicosis. To examine whether thyroid-stimulating TSH receptor antibody (TSAb) or human chorionic gonadotropin (hCG), which also has thyroid-stimulating activity (TSA), is responsible for this early aggravation, the respective TSA due to TSAb or hCG were evaluated with a sensitive cAMP accumulation assay using FRTL-5 cells. TSA, which was detectable in all of 11 women in normal early pregnancy, correlated positively with serum hCG level, but was abolished completely by the pretreatment of serum samples with the solid-phase hCG antibody coupled with Sepharose-4B. Total TSA in the model samples of mixture of Graves' and pregnant sera (Gr + Preg), was reduced by the pretreatment with the solid-phase antibody, just corresponding with the reduction in hCG-induced TSA. Total TSA in early pregnant sera in 15 patients with Graves' disease, decreased significantly but was still positive even by the pretreatment with the hCG antibody. Pregnancy-associated changes in TSA was examined serially in a patient with Graves' disease, and hCG-induced TSA increased predominantly along with the serum thyroid hormone in early aggravation period. These data indicate that (1) the respective TSA due to TSAb or hCG can be differentially measured by using the solid-phase hCG antibody and (2) hCG plays an important role for aggravation of Graves' thyrotoxicosis in early pregnancy.

Animals↗
PubMed1992

[Determination of serum interleukin-6 concentration by an enzyme-linked immunosorbent assay in patients with paraproteinemia].

A sensitive enzyme-linked immunosorbent assay of human interleukin-6 (IL-6) was developed to measure the serum IL-6 by Fujirebio INC. Its sensitivity was 3 pg/ml and its analytical range was from 3 to 200 pg/ml. Its precision, reproducibility, and sensitivity were quite satisfactory. The serum IL-6 levels in 200 normal individuals were less than 3 pg/ml. Serum IL-6 concentration in patients with malignant and benign monoclonal gammopathy (BMG) was determined by an ELISA. Serum IL-6 concentration in patients with Bence Jones protein (BJP) type multiple myeloma (MM) (n = 12) was 12.3 +/- 12.7 (mean +/- SD) pg/ml, BJP and IgG type MM (n = 4) 11.5 +/- 5.8 pg/ml, IgM type MM (n = 11) 11.1 +/- 17.5 pg/ml and IgA type MM (n = 4) 4.0 +/- 1.4 pg/ml. They were significantly higher in BJP, BJP and IgG, and IgM types than in normal individuals. The cases with the serum IL-6 of more than 10 pg/ml were move frequent in MM (32.8%) than in BMG (16.3%). The correlation between the serum IL-6 and C-reactive protein (CRP) was r = 0.563 in patients with MM (n = 61) and r = 0.498 in BMG (n = 43). Besides, during the clinical course of a patient with IgG-lambda and BJP-lambda type MM, serum IL-6 concentration responded more sharply than CRP and WBC on candida infection. The measurement of serum IL-6 therefore, seemed not useful for differential diagnosis of monoclonal gammopathies, but it seemed useful as an acute phase protein as well as CRP.

Enzyme-Linked Immunosorbent Assay↗
PubMed1992

[Effect of coix seed on the changes in peripheral lymphocyte subsets].

Coix seed has been used in patients with verruca vulgaris and verruca planae juveniles, which have been considered to be induced by viral infection. Moreover, coixenolide, component in the seeds of coix, was reported to show anti-tumor activity. Possibly coix seed may have some influence on the cytotoxic activity of peripheral lymphocytes but there has been no data on this. Then we investigated the changes in number of cytotoxic lymphoid cells in seven volunteers before, during (four weeks) and after taking six coix seed tablets. Lymphocyte subsets were analyzed with monoclonal antibodies using a flow cytometer. The level of CD3+CD56+ (MHC-non restricted cytotoxic T cells) markedly increased at four weeks (before 1.9 +/- 0.5% vs four weeks 4.2 +/- 0.7%, p less than 0.01). The level of CD16+CD57- (the mature, most active natural killer cells) increased at three weeks (before 4.5 +/- 0.8% vs three weeks 5.2 +/- 0.8%, p less than 0.05). The level of CD3-CD56+ (natural killer cells) and the level of CD16+CD57+ (the variable active natural killer cells) decreased at one week and returned to normal level thereafter (before 13.7 +/- 2.1% vs one week 11.2 +/- 1.5%, p less than 0.05; before 8.8 +/- 1.5% vs one week 6.9 +/- 1.3%, p less than 0.05, respectively). These results indicate that coix seed modulate the peripheral blood lymphocyte subsets and may be effective to virus disease through the enhancement of cytotoxic activity.

Drugs, Chinese Herbal↗
PubMed1991

Effect of a novel squalene epoxidase inhibitor, NB-598, on the regulation of cholesterol metabolism in Hep G2 cells.

We have reported previously that NB-598 competitively inhibits human squalene epoxidase and strongly inhibits cholesterol synthesis from [14C]acetate in cultured cells. Furthermore, multiple oral administration of NB-598 decreased serum cholesterol levels in dogs (Horie, M., Tsuchiya, Y., Hayashi, M., Iida, Y., Iwasawa, Y., Nagata, Y., Sawasaki, Y., Fukuzumi, H., Kitani, K., and Kamei, T. (1990) J. Biol. Chem. 265, 18075-18078). In the present study, the effects of NB-598 on 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase and low-density-lipoprotein (LDL) receptor were examined using a human hepatoma cell line Hep G2. Incubation of Hep G2 cells with NB-598 for 18 h increased HMG-CoA reductase activity in a dose-dependent manner. However, the increase in activity induced by NB-598 was lower than that induced by L-654,969 (a potent HMG-CoA reductase inhibitor), although NB-598 inhibited cholesterol synthesis more potently than L-654,969. On the other hand, HMG-CoA reductase mRNA was increased to the same extent by both inhibitors. These results demonstrate that NB-598 does not inhibit the synthesis of non-sterol derivative(s) of mevalonate, which regulate HMG-CoA reductase activity at the post-transcriptional level. NB-598 increased the binding of 125I-LDL to Hep G2 cells. LDL receptor mRNA was also induced by NB-598. In the presence of LDL or cycloheximide, NB-598 did not increase LDL receptor activity. These results demonstrate that the induction of LDL receptor activity by NB-598 is due to increases in mRNA and protein through the inhibition of cholesterol synthesis at the squalene epoxidase step. From these observations, squalene epoxidase inhibitor is expected to be highly effective in the treatment of hypercholesterolemia and also is very useful as a research tool for studying the regulation of cholesterol metabolism.

Acetates↗
PubMed1991

Synthesis and biological properties of carba-analogs of heat-stable enterotoxin (ST) produced by enterotoxigenic Escherichia coli.

Analogs of a heat-stable enterotoxin (ST) that have a CH2-S linkage instead of an S-S linkage in the molecule were synthesized by conventional methods. The synthetic peptides showed toxicity, assayed as induction of fluid secretion in suckling mice, although their toxicities were hundredth that of native ST. This finding implies that ST is not recognized by its receptor protein through an exchange reaction between its disulfide linkages and thiol-groups of its receptor protein(s), but through hydrophobic or electrostatic interactions.

Amino Acid Sequence↗
PubMed1991

Changes in natural killer cell activity in normal pregnant and postpartum women: increases in the first trimester and postpartum period and decrease in late pregnancy.

Changes in the activity and number of natural killer (NK) cells in peripheral blood in normal pregnant and postpartum women were examined. NK activity was measured in a 4-h 51Cr-release assay and evaluated by conventional relative lytic units and absolute lytic units which represent the total NK activity within a fixed volume of circulating blood. The number of NK cells was analyzed with FITC-conjugated monoclonal antibodies and by use of an automated flow cytometer. Unexpectedly, the relative NK activity increased in the first trimester and also for 1 month postpartum compared to the activity in normal non-pregnant controls. On the other hand, absolute NK activity decreased in the third trimester compared to the activity in normal non-pregnant controls. The percentage of CD57+ cells decreased in the second trimester, but the percentage of CD16+ cells did not change during pregnancy or the postpartum period. The absolute counts of CD57+ cells and CD16+ cells decreased in the second and third trimesters and increased transiently in the postpartum period. These findings indicate that the increased NK activity in the first trimester and at 1 month postpartum is induced by increased cytotoxic activity of individual NK cells, and that the decreased NK activity in late pregnancy is induced by a decrease in the numbers of NK cells. These physiological changes may play an important role in implantation in early pregnancy, protection of the fetal allograft in late pregnancy and in the natural defense against infection during the puerperal period.

Adult↗
PubMed1991

Glycoprotein C of herpes simplex virus type 1 is essential for the virus to evade antibody-independent complement-mediated virus inactivation and lysis of virus-infected cells.

Glycoprotein C (gC) of herpes simplex virus type 1 (HSV-1) is a receptor for the complement component C3b. We have previously isolated HSV-1 gC- strains (TN1, TN2 and TN3) from a patient with recurrent keratitis at three different times. These are very rare isolates because gC was thought to be essential for the virus in vivo. To determine whether gC modifies the interaction of complement with cell-free virus or virus-infected cells, we constructed gC+ recombinant viruses in which the intact gC gene of strain KOS was inserted into the TN1 virus genome. TN1 virus was inactivated by complement and TN1 virus-infected cells were lysed by complement; however, gC+ recombinant viruses became resistant to these effects of complement. These results suggest a role for gC in protection of both the virion envelope and the infected cell surface against damage by complement. TN1 virus was inactivated by complement from rats (Wistar, WKA, F344 and SD), guinea-pigs (Hartley) and humans, but not by complement from mice (C3H, DDD and BALB/c), which indicates that mice seem to be inappropriate as an experimental model for the study of HSV infection in which complement factors need to be considered.

Animals↗