Biomedical subjects

M Sugano

Publications and source records attributed to M Sugano.

At least 73 records · Page 4Linked to original sources

PubMed1999

Improvement of molar ratio of branched-chain amino acids to tyrosine (BTR) associated with liver fibrosis in chronic hepatitis C patients treated with interferon-alpha.

The molar ratio of branched-chain amino acids (BCAA) to tyrosine (BTR), which has recently been possible to easily determine by an enzymatic method, can be clinically used as a substitute for that of BCAA to aromatic amino acids (AAA). We used this method to investigate the diagnostic implications of serum BTR in patients with chronic hepatitis C treated with interferon-alpha. There was a good correlation between BTR and staging (fibrosis) scores both before and after treatment. BTR increased significantly at 24 months after treatment in the responder group (P < 0.01). Moreover, a significant increase in BTR was observed in patients with improved staging (P = 0.015), but not grading (necroinflammatory), scores. BTR in chronic hepatitis C patients seems to be reflected by the extent of liver fibrosis, and, in the responder group, it can be improved, together with liver fibrosis, by interferon-alpha treatment.

Adult↗

PubMed1999

Dietary effect of conjugated linoleic acid on lipid levels in white adipose tissue of Sprague-Dawley rats.

We examined the effect of dietary conjugated linoleic acid (CLA) on lipid parameters in the liver, white adipose tissue (WAT) and brown adipose tissue (BAT) of Sprague-Dawley rats and found that it reduced the levels of triglycerides and non-esterified fatty acid in the liver and WAT without significant change in the BAT lipid levels. These results suggest that CLA has an obesity-preventing action.

Adipocytes↗

PubMed1999

Dietary effect of EPA-rich and DHA-rich fish oils on the immune function of Sprague-Dawley rats.

The dietary effect of fish oils (FOs) rich in eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) on the immune function of Sprague-Dawley rats was compared with that of safflower oil. After 3 weeks of feeding at the 10% level of a dietary fat, the IgG and IgM production by splenocytes and IgG production by mesenteric lymph node (MLN) lymphocytes were significantly higher in the FO-fed rats, while no significant difference was found in IgA or IgE productivity by both the spleen and MLN lymphocytes. In the FO-fed rats, peritoneal exudate cells released a lower amount of LTB4, reflecting their lower arachidonic acid level, and a higher amount of LTB5, reflecting their higher EPA level in phospholipids. On these EPA-rich FO exerted a stronger effect than DHA-rich FO immune functions.

Adjuvants, Immunologic↗

PubMed1999

Dietary effect of tocopherols and tocotrienols on the immune function of spleen and mesenteric lymph node lymphocytes in Brown Norway rats.

The immunoregulatory effects of dietary alpha-tocopherol (Toc) and tocotrienols (T-3) on humoral and cell-mediated immunity and cytokine productions were examined in Brown Norway rats. We found that the IgA and IgG productivity of spleen and mesenteric lymph node (MLN) lymphocytes was significantly enhanced in the rats fed on Toc or T-3, irrespective of concanavalin A (Con A) stimulation of the lymphocytes. On the contrary, the IgE productivity of lymphocytes from the rats fed on Toc or T-3 was less without Con A stimulation, but was greater in the presence of Con A, especially in the T-3 group. Toc or T-3 feeding significantly decreased the proportion of CD4+ T cells and the ratio of CD4+/CD8+ in both spleen and MLN lymphocytes of the rats fed on Toc or T-3. The interferon-gamma productivity of MLN lymphocytes was higher in the rats fed on Toc or T-3 than in those fed on a control diet in the presence of Con A, while that of spleen lymphocytes was lower in the rats fed on Toc or T-3. In addition, T-3 feeding decreased the productivity of tumor necrosis factor-alpha of spleen lymphocytes, while it enhanced the productivity of MLN lymphocytes. These results suggest that oral administration of Toc and T-3 affects the proliferation and function of spleen and MLN lymphocytes.

Animals↗

PubMed1999

Dietary effect of guar gum and its partially hydrolyzed product on the lipid metabolism and immune function of Sprague-Dawley rats.

The dietary effect of the water-soluble dietary fibers (WSDF), guar gum, partially hydrolyzed guar gum (PHGG), glucomannan, highly methoxylated (HM) pectin, on the serum lipid level and immunoglobulin (Ig) production of Sprague-Dawley rats was compared with that of water-insoluble cellulose. Although serum total cholesterol and triglyceride levels were significantly lower in the rats fed with WSDF than in those fed with cellulose, a decrease in the level of phospholipids was only observed in the rats that had been fed on guar gum or glucomannan. In addition, all WSDF feeding enhanced IgA productivity in the spleen and mesenteric lymph node lymphocytes, although the increase in serum IgA level was only observed in the rats fed on WSDF, and not on PHGG. When mesenteric lymph node lymphocytes were cultured in the presence of various concentrations of guar gum or glucomannan, no significant increase in Ig production was apparent. These data suggest that WSDF indirectly enhanced the Ig production of lymphocytes, and that serum lipid reduction and IgA production-enhancing activities of WSDF were dependent on their molecular sizes.

Animals↗

PubMed1999

Effect of dietary antioxidants on serum lipid contents and immunoglobulin productivity of lymphocytes in Sprague-Dawley rats.

Sprague-Dawley rats were fed alpha-tocopherol, tocotrienol, or quercetin to examine their dietary effects on serum lipid contents and immunoglobulin productivity. In tocotrienol or quercetin groups, serum triglyceride was lower than in the none group. Moreover, in the alpha-tocopherol group, serum IgA level and IgA productivity of MLN lymphocytes were high, while in the tocotrienol group, IgM productivity of spleen lymphocytes and IgA, IgG, and IgM productivity of MLN lymphocytes were high. Thus, we suggested each antioxidant had different effects in rats.

Animals↗

PubMed1999

Effect of dietary sesamin on metabolic fate of an exogenous linolelaidic acid in perfused rat liver.

To estimate the relative significance of exogenous and endogenous fatty acid substrates in decreasing hepatic triacylglycerol secretion after sesamin feeding, livers from rats fed diets supplemented with and without sesamin (sesamin: episesamin, 1:1, w/w) were perfused in the presence and absence of an exogenous di-trans isomer of linoleic acid (linolelaidic acid, trans,trans-9,12-octadecadienoic acid). Both exogenous trans fatty acid and dietary sesamin, as compared with respective controls, resulted in a marked increase in hepatic ketogenesis; however, the beta-hydroxybutyrate to acetoacetate ratio was elevated by exogenous fatty acid and decreased by dietary sesamin. On the other hand, hepatic secretions of triacylglycerol, phospholipid and cholesterol were markedly lowered in rats fed sesamin, especially when exogenous fatty acid substrate was provided. The relative significance of the exogenous fatty acid was observed in the dietary sesamin-induced decrease in hepatic secretion of triacylglycerol. These results suggest that increased fatty acid oxidation by dietary sesamin, as reflected by enhanced ketone body production, leads to decreased partition of fatty acid substrates to the esterification pathways, and this in turn reduces the synthesis and secretion of triacylglycerol. The altered metabolism of exogenous fatty acids in the liver was therefore a major determinant for the synthesis and secretion of triacylglycerol.

Animals↗

PubMed1999

Apolipoprotein E in cerebrospinal fluid: relation to phenotype and plasma apolipoprotein E concentrations.

BACKGROUND: Apolipoprotein (apo) E may be related to the development of Alzheimer disease, but data on apoE in cerebrospinal fluid (CSF) are limited. The aim of the present study was to measure apoE in CSF and relate its concentrations to apoE phenotype and CSF lipids. METHODS: We adapted an assay for CSF apoE sensitivity using an ELISA. It allowed us to measure CSF apoE with sufficient reproducibility and precision. RESULTS: The within- and between-run CVs were <7%, and the detection limit was 0.025 mg/L. No cross-reaction was found for other apolipoproteins. No significant differences related to sex or apoE phenotype were observed in the CSF apoE concentration. The mean CSF apoE concentration was significantly higher in the 0-5 year group (n = 6; 18.47 +/- 1.14 mg/L, mean +/- SD) than in the >5 year group (n = 34; 8.82 +/- 3.31 mg/L). The mean concentrations of total cholesterol (TC) and phospholipid (PL) in CSF were 2.68 +/- 2.16 and 6.50 +/- 2.84 mg/L (n = 52), respectively. Although no significant differences in TC or PL in the CSF were found with respect to sex or age, the concentrations in subjects with the apoE phenotype E4/E3 were significantly lower than in those with E3/E3 and E3/E2. The concentrations of apoE, TC, and PL in CSF did not correlate with those in plasma. The time-related fluctuations in CSF apoE were independent of those in total protein and IgG. CSF apoE was significantly correlated with TC and PL concentrations in the CSF, but not with the number of cells in the CSF. CONCLUSIONS: These findings support the idea that apoE and lipids are unable to cross the blood-brain barrier and that their concentrations in CSF may reflect production in central nervous tissue.

Adolescent↗

PubMed1998

Effect of antisense oligonucleotides against cholesteryl ester transfer protein on the development of atherosclerosis in cholesterol-fed rabbits.

Cholesteryl ester transfer protein (CETP) is the enzyme that facilitates the transfer of cholesteryl ester from high density lipoprotein (HDL) to apolipoprotein B (apoB)-containing lipoproteins. However, the exact role of CETP in the development of atherosclerosis has not been determined. In the present study, we examined the effect of the suppression of increased plasma CETP by intravenous injection with antisense oligodeoxynucleotides (ODNs) against CETP targeted to the liver on the development of atherosclerosis in rabbits fed a cholesterol diet. The ODNs against rabbit CETP were coupled to asialoglycoprotein (ASOR) carrier molecules, which serve as an important method to regulate liver gene expression. Twenty-two male Japanese White rabbits were used in the experiment. Eighteen animals were fed a standard rabbit chow supplemented with 0.3% cholesterol throughout the experiment for 16 weeks. At 8 weeks, they were divided into three groups (six animals in each group), among which the plasma total and HDL cholesterol concentrations did not significantly change. The control group received nothing, the sense group were injected with the sense ODNs complex, and the antisense group were injected with the antisense ODNs complex, respectively, for subsequent 8 weeks. ASOR. poly(L-lysine) ODNs complex were injected via the ear veins twice a week. Four animals were fed a standard rabbit diet for 16 weeks. The total cholesterol concentrations and the CETP mass in the animals injected with antisense ODNs were all significantly decreased in 12 and 16 weeks compared with those injected with sense ODNs and the control animals. The HDL cholesterol concentrations measured by the precipitation assay did not significantly change among the groups fed a cholesterol diet, and triglyceride concentrations did not significantly change in the four groups. However, at the end of the study, when the HDL cholesterol concentrations were measured after the isolation by ultracentrifugation and a column chromotography, they were significantly higher in the animals injected with antisense ODNs than in the animals injected with sense ODNs and in the control animals. A reduction of CETP mRNA and an increase of LDL receptor mRNA in the liver were observed in the animals injected with antisense ODNs compared with those injected with sense ODNs and the control animals. Aortic cholesterol contents and the aortic percentage lesion to total surface area were significantly lower in the animals injected with antisense ODNs than in the animals injected with sense ODNs and in the control animals. These findings showed for the first time that suppression of increased plasma CETP by the injection with antisense ODNs against CETP coupled to ASOR carrier molecules targeted to the liver could thus inhibit the atherosclerosis possibly by decreasing the plasma LDL + very low density lipoprotein (VLDL) cholesterol in cholesterol-fed rabbits.

Animals↗

PubMed1998

High proportion of missense mutations of the BRCA1 and BRCA2 genes in Japanese breast cancer families.

Mutations in either of two recently identified genes, BRCA1 and BRCA2, are thought to be responsible for approximately two-thirds of all cases of autosomal-dominantly inherited breast cancer. To examine the nature and frequency of BRCA1 and BRCA2 mutations in Japanese families exhibiting a high incidence of breast cancer, we screened 78 unrelated families in this category for mutations of these two genes. Examining the entire coding sequences as well as exon-intron boundaries of both genes by polymerase chain reaction (PCR) single-strand conformation polymorphism (SSCP) and multiplex-SSCP analysis, we identified possible disease-causing alterations in BRCA1 among affected members of 15 families and in BRCA2 in another 14 families. In 15 of those 29 families, the affected individuals carried missense mutations, although most germline mutations reported worldwide have been deletions or nonsense mutations. Our results, indicating that missense mutations of BRCA1 and BRCA2 tend to predominate over frameshifts or nonsense mutations in Japanese breast cancer families, will contribute significantly to an understanding of mammary tumorigenesis in Japan, and will be of vital importance for future genetic testing.

BRCA2 Protein↗

PubMed1998

Conjugated linoleic acid modulates tissue levels of chemical mediators and immunoglobulins in rats.

The effects of conjugated linoleic acid (CLA) on the levels of chemical mediators in peritoneal exudate cells, spleen and lung, and the concentration of immunoglobulins in mesenteric lymph node and splenic lymphocytes and in serum were examined in rats. After feeding diets containing either 0 (control), 0.5 or 1.0% CLA for 3 wk, there was a trend toward a reduction in the release of leukotriene B4 (LTB4) from the exudate cells in response to the dietary CLA levels. However, CLA did not appear to affect the release of histamine. A similar dose-response pattern also was observed in splenic LTB4, lung LTC4 and serum prostaglandin E2 levels, and the differences in these indices between the control and 1.0% CLA groups were all statistically significant. The reduction by CLA of the proportions of n-6 polyunsaturated fatty acids in peritoneal exudate cells and splenic lymphocyte total lipids seems to be responsible at least in part for the reduced eicosanoid levels. Splenic levels of immunoglobulin A (IgA), IgG, and IgM increased while those of IgE decreased significantly in animals fed the 1.0% CLA diet. This was reflected in the serum levels of immunoglobulins. The levels of IgA, IgG, and IgM in mesenteric lymph node lymphocytes increased in a dose-dependent manner, while IgE was reduced in those fed the higher CLA intake. However, no differences were seen in the proportion of T-lymphocyte subsets of mesenteric lymph node. These results support the view that CLA mitigates the food-induced allergic reaction.

Animals↗

PubMed1998

Dietary oxidized cholesterol modulates cholesterol metabolism and linoleic acid desaturation in rats fed high-cholesterol diets.

The interactive effect of high dietary levels of oxidized cholesterol on exogenous cholesterol and linoleic acid metabolism was examined in male 4-wk-old Sprague-Dawley rats given high-cholesterol diets. The rats were pair-fed purified diets free of or containing either 0.5% cholesterol alone or both 0.5% cholesterol and 0.5% oxidized cholesterol mixture (containing 93% oxidized cholesterol) for 3 wk. Hepatic 3-hydroxy-3-methylglutaryl CoA reductase activity was reduced in rats given cholesterol alone or both cholesterol and oxidized cholesterol. However, hepatic cholesterol 7alpha-hydroxylase activity was lowered only when rats were given both cholesterol and oxidized cholesterol, although dietary cholesterol increased this activity. Reflecting this effect, acidic steroid excretion was lowest among the groups of rats given cholesterol and oxidized cholesterol. On the other hand, the activity of hepatic delta6 desaturase, a key enzyme in the metabolism of linoleic acid to arachidonic acid, was increased in rats given both cholesterol and oxidized cholesterol, although dietary cholesterol alone lowered its activity. As a result, the delta6 desaturation index, 20:3n-6 + 20:4n-6/18:2n-6, in liver and serum phospholipids tended to be higher in the group fed both cholesterol and oxidized cholesterol than in the one fed cholesterol alone. Thus, dietary oxidized cholesterol significantly modulated exogenous cholesterol metabolism and promoted linoleic acid desaturation even when it was given at high levels together with a high cholesterol diet.

Animals↗

PubMed1998

Prenylflavonoids: a new class of non-steroidal phytoestrogen (Part 1). Isolation of 8-isopentenylnaringenin and an initial study on its structure-activity relationship.

Bioassay-guided fractionation of a methanolic extract of a Thai crude drug, derived from heartwood of Anaxagorea luzonensis A. Gray (Annonaceae), resulted in the isolation of 8-isopentenylnaringenin (1) as an estrogen agonist with a activity of about an order of magnitude greater than genistein. Various flavonoids possessing isopentenyl side chains in the A-ring have been prepared and evaluated for their ability to bind estrogen receptor. In addition, enantiomers of 1 were separated and the respective enantiomers were assayed. These studies have demonstrated that the presence of an 8-isopentenyl group is an important factor for binding. Flavones, flavanones and flavonols having an isopentenyl substituent at C-8 exhibited an appreciable affinity for estrogen receptor. Conversely, isoflavones possessing an 8-isopentenyl substituent at C-8 did not show this activity. Movement of the isopentenyl group from position 8 to 6 resulted in loss of the activity. No significant difference was observed between 2(S)- and 2(R)-enantiomers of 1 in their binding affinity. Prenylflavonoids are reported to possess a wide range of biological activities; however, estrogenic activity has not been described.

Breast Neoplasms↗

PubMed1998

Prenylflavonoids: a new class of non-steroidal phytoestrogen (Part 2). Estrogenic effects of 8-isopentenylnaringenin on bone metabolism.

In order to examine whether 8-isopentenylnaringenin (1), which has been proven to possess estrogen agonist activity in in vitro tests, also produces in vivo estrogenic properties, the effects of 1 on uterus and on bone metabolism were determined in ovariectomized rats. Rats were ovariectomized and treated with 1 at 30 mg/kg/day subcutaneously for two weeks or 17 beta-estradiol at 0.01 mg/kg/day subcutaneously for two weeks. Ovariectomy resulted in an increase in urinary excretion of bone resorption markers (hydroxyproline, pyridinoline and deoxypyridinoline) and a decrease in bone mineral density of the proximal tibia as well as reduced uterine weight. Treatment with 1 or 17 beta-estradiol completely suppressed these ovariectomy-induced bone and uterine changes in a qualitatively similar manner. These results demonstrate that 1 acts as an estrogen agonist in the uterus as well as in bone in vivo.

Amino Acids↗

PubMed1998

Inhibition of cholesterol absorption by plant sterols for mass intervention.

Plant sterols and stanols lower serum cholesterol by inhibiting intestinal absorption of cholesterol. Because of their safety and efficacy, their application for mass intervention is promising. The use of fatty acid esters of stanols is particularly helpful because stanols readily mix with dietary fats in this form and their hypocholesterolemic efficacy is greater than in the free form.

Animals↗

PubMed1998

Clinical significance of serum hyaluronic acid as a fibrosis marker in chronic hepatitis C patients treated with interferon-alpha: histological evaluation by a modified histological activity index scoring system.

The aim of the present study was to investigate the histological changes effected by interferon (IFN) treatment and to evaluate the clinical significance of serum hyaluronic acid (HA) as a marker of fibrosis. Forty-nine patients with chronic hepatitis C treated with IFN-alpha were divided into three groups according to the existence of viraemia: sustained complete responders (CR), complete responders with relapse (PR) and non-responders (NR). Needle biopsy sections of the liver taken before and at the end of IFN treatment were assessed according to the modified histological activity index (HAI) scoring system. Serum fibrosis markers, including HA, were measured at needle biopsies. Biopsies of CR at the end of treatment showed a significant improvement in fibrosis and necroinflammatory scores. More significant correlation was observed between fibrosis scores and serum levels of HA before IFN treatment (r = 0.607, P < 0.0001) than those between fibrosis scores, on the one hand, and peptide of type III procollagen (PIIIP; r = 0.531, P = 0.0004) or type IV collagen 7S domain (type IV-C; r = 0.241, P = 0.1062) on the other. Moreover, serum HA levels fell significantly in patients in whom fibrosis improved (P = 0.011). This is the first paper describing the advantages of the modified HAI scoring system over others in estimating the effect of IFN-alpha; the results also indicate that serum HA can be useful in monitoring liver fibrosis in chronic hepatitis C patients treated with IFN-alpha.

Adult↗

PubMed1998

Intravenous injection with antisense oligodeoxynucleotides against angiotensinogen decreases blood pressure in spontaneously hypertensive rats.

In the renin-angiotensin system, renin is known to cleave angiotensinogen to generate angiotensin I, which is the precursor of angiotensin II. Angiotensin II is a vasoactive peptide that plays an important role in blood pressure. On the other hand, the liver is the major organ responsible for the production of angiotensinogen in spontaneously hypertensive rats (SHR). To test the hypothesis that a reduction of angiotensinogen mRNA in the liver by antisense oligodeoxynucleotides (ODNs) may affect both plasma angiotensinogen and angiotensin II levels, as well as blood pressure, we intravenously injected antisense ODNs against rat angiotensinogen coupled to asialoglycoprotein carrier molecules, which serve as an important regulator of liver gene expression, into SHR via the tail vein. The SHR used in the present study were studied at 20 weeks of age and were fed a standard diet throughout the experiment. Plasma angiotensinogen, angiotensin II concentrations, and blood pressure all decreased from the next day until up to 5 days after the injection of antisense ODNs. These concentrations thereafter returned to baseline by 7 days after injection. A reduction in the level of hepatic angiotensinogen mRNA was also observed from the day after injection until 5 days after injection with antisense ODNs. However, in the SHR injected with sense ODNs, plasma angiotensinogen, angiotensin II concentrations, and blood pressure, as well as hepatic angiotensinogen mRNA, did not significantly change throughout the experimental period. Although the exact role of angiotensinogen in hypertension still remains to be clarified, these findings showed that intravenous injection with antisense ODNs against angiotensinogen coupled to asialoglycoprotein carrier molecules targeted to the liver could thus inhibit plasma angiotensinogen levels and, as a result, induce a decrease in blood pressure in SHR.

Angiotensinogen↗

PubMed1998

Interaction of mRNAs for angiotensin II type 1 and type 2 receptors to vascular remodeling in spontaneously hypertensive rats.

We administered angiotensin II (Ang II) receptor type 1 (AT1) blockade (losartan, 40 mg x kg-1 x d-1), type II receptor (AT2) blockade (PD123319, 100 mg x kg-1 x d-1), or angiotensin-converting enzyme (ACE) inhibitor (enalapril, 30 mg x kg-1 x d-1) to spontaneously hypertensive rats (SHR) from 10 to 20 weeks of age. Control SHR and Wister-Kyoto rats (WKY) received a placebo for the same period. At the end of treatment, losartan and enalapril were both found to have significantly reduced the arterial systolic blood pressure and the collagen concentration to the level of WKY, whereas PD123319 had no effect. Enalapril and PD123319 significantly reduced the media cross-sectional area of the aorta in comparison to that of untreated SHR, which was still larger than that of the WKY; however, losartan did not change it. Using reverse transcription-polymerase chain reaction, we next examined the mRNA expressions for ACE, AT1 receptor, and AT2 receptor in experimental animals. We observed significantly enhanced mRNA expression for AT1 and AT2 receptors and ACE in untreated SHR compared with WKY. The AT1 mRNA level was also significantly decreased in the SHR treated with either losartan or enalapril, whereas the AT2 mRNA level was significantly decreased in the SHR treated with either PD123319 or enalapril in comparison to untreated SHR. The level of ACE mRNA was significantly decreased only in the SHR treated with enalapril. These results indicate that AT1 receptor, but not AT2 receptor, plays a crucial role in the remodeling of matrix tissue, while AT2 receptor may play a role in the development of hypertrophy of smooth muscle in aorta in SHR, and that the reduction of hypertrophy of smooth muscle does not fully account for the suppression of hypertension.

Angiotensin Receptor Antagonists↗