Biomedical subjects

M Sugano

Publications and source records attributed to M Sugano.

At least 109 records · Page 6Linked to original sources

PubMed1997

Effects of hepatic HDL-related mRNAs on plasma prebeta HDL in cholesterol-fed rabbits.

This study was undertaken to determine; 1) the effect of cholesterol enriched diet on prebeta-migrating (prebeta) HDL levels, 2) the effect of the diet on plasma proteins and/or activities likely associated with prebeta HDL (cholesteryl transfer protein (CETP), lecithin-cholesterol acyltransferase (LCAT) and apolipoprotein (apo)A-I), 3) the effect of the diet on the corresponding hepatic mRNAs and 4) the correlation between the hepatic mRNAs and prebeta HDL. Rabbits were fed 0.1% (low) cholesterol (LC group, n = 6) or 0.5% (high) cholesterol diet (HC group, n = 6) for 6 weeks. Plasma CETP activities, plasma total apoA-I and prebeta apoA-I concentrations in the HC group were significantly increased (58.95 +/- 2.37%, 191.52 +/- 13.93 mg/dl, 44.21 +/- 1.14 mg/dl, respectively) compared with the LC group (39.36 +/- 3.62%, 152.85 +/- 8.61 mg/dl, 30.12 +/- 2.79 mg/dl, respectively)(p < 0.05). Plasma LCAT activities did not differ significantly (56.65 +/- 7.19 vs 57.41 +/- 8.21; HC vs LC). Hepatic CETP, LCAT and apoA-I mRNA levels were determined using reverse transcription polymerase chain reaction (RT-PCR). Hepatic CETP mRNA levels, compared to GAPDH mRNA levels as a control, were increased in the HC group (2.226 +/- 0.115) compared with the LC group (1.649 +/- 0.170) (p < 0.05), while hepatic LCAT and apoA-I mRNA levels were unchanged. Thus, plasma concentration of prebeta HDL, CETP activity and the amount of hepatic CETP mRNA were increased in response to the dietary intake of cholesterol. Multiple regression analyses showed that only hepatic CETP mRNA levels had a positive correlation with plasma prebeta HDL concentration (p = 0.04). These results indicate that individual variations in hepatic CETP mRNA levels in rabbits fed a cholesterol diet probably has a major influence on the determination of plasma prebeta HDL concentration.

Animal Feed↗

PubMed1996

Structure-activity relationships of phomactin derivatives as platelet activating factor antagonists.

Phomactins, natural products isolated from the culture broth of marine fungus Phoma sp., were found to be active as PAF antagonists. This unique carbon skeleton led us to investigate the structure-activity relationship demonstrating that the lipophilicity at C-(7-8), acetoxy, (methoxycarbonyl)oxy, and 3-isoxazolyloxy substitution at C-20, and 2-beta-OH configuration at C-2 are all required for the enhancement of inhibitor activity.

Epoxy Compounds↗

PubMed1996

The effects of renin-angiotensin system inhibition on aortic cholesterol content in cholesterol-fed rabbits.

To investigate how the renin-angiotensin system (RAS) might be involved in cholesterol-induced atherosclerosis, we studied the effects of a nonsulhydryl angiotensin converting enzyme (ACE) inhibitor, enalapril, and an angiotensin II receptor antagonist, E-4177, in cholesterol fed rabbits. Japanese white rabbits were randomly divided into four groups with the following dietary regimens: group A (n = 8) received a standard diet; group B (n = 8) had a 0.5% cholesterol diet; group C (n = 8) had a 0.5% cholesterol diet plus enalapril (10 mg/kg/day, p.o.); group D (n = 8) received a 0.5% cholesterol diet plus E-4177 (20 mg/kg/day, p.o.) and were fed these diets for 5 weeks. Enalapril or E-4177 had no significant effect on either the total plasma or the high density lipoprotein (HDL) cholesterol concentrations. However, the aortic cholesterol content in groups C and D was equally significantly less than that in group B. The plasma and aortic ACE activities were significantly reduced only in group C compared with those in the other groups. The aortic ACE mRNA and AT1 mRNA levels were assessed by a reverse transcription polymerase chain reaction (RT-PCR). The aortic ACE mRNA level was only significantly less in group C than in any of the other groups. The aortic AT1 mRNA level increased significantly in group B compared with that in group A and was significantly and equally reduced in both groups C and D compared with that in group B. These data indicate that angiotensin II rather than ACE may therefore be related to aortic cholesterol content. It follows therefore that the inhibition of angiotensin II by either ACE inhibitor or angiotensin II (type 1) receptor antagonist may play a role in prevention of atherosclerosis.

Angiotensin II↗

PubMed1996

Changes in plasma lipoprotein cholesterol levels by antisense oligodeoxynucleotides against cholesteryl ester transfer protein 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 apoB-containing lipoproteins and also affects the low density lipoprotein metabolism. On the other hand, the liver is the major tissue responsible for the production of CETP (CETP mRNA) in rabbits. To test the hypothesis that a reduction of CETP mRNA in the liver by antisense oligodeoxynucleotides (ODNs) may affect the plasma lipoprotein cholesterol levels, we intravenously injected antisense ODNs against rabbit CETP coupled with asialoglycoprotein carrier molecules, which serve as an important method to regulate liver gene expression, to cholesterol-fed rabbits via their ear veins. All rabbits were fed a standard rabbit chow supplement with 0.1% cholesterol for 10 weeks before and throughout the experiment. After injecting rabbits with antisense ODNs, the plasma total cholesterol concentrations and plasma CETP activities all decreased at 24, 48, and 96 h, whereas the plasma HDL cholesterol concentrations increased at 48 h. A reduction in the hepatic CETP mRNA was also observed at 6, 24, and 48 h after the injection with antisense ODNs. However, in the rabbits injected with sense ODNs, the plasma total and HDL cholesterol concentrations and the plasma CETP activities did not significantly change, and the hepatic CETP mRNA did not change either throughout the experimental period. Although the exact role of CETP in the development of atherosclerosis remains to be clarified, these findings showed for the first time that the intravenous injection with antisense ODNs against CETP coupled to asialoglycoprotein carrier molecules targeted to the liver could thus inhibit plasma CETP activity and, as a result, could induce a decrease in the plasma low density lipoprotein and very low density lipoprotein cholesterol and an increase in the plasma HDL cholesterol in cholesterol-fed rabbits.

Animals↗

PubMed1996

Regression of hypertrophy after myocardial infarction is produced by the chronic blockade of angiotensin type 1 receptor in rats.

The efficacy of angiotensin converting enzyme (ACE) inhibitors is well known to prevent the formation of angiotensin II (Ang II) by these agents. The objective of the present study was to evaluate the hemodynamic, biochemical, and morphological responses to Ang II receptor blockade with E-4177, 3-[(2'-carboxybiphenyl-4-yl) methyl]-2-cyclopropyl-7-methyl 3H-imidazol[4,5-b] pyridine, in rats with a healing myocardial infarction that had been induced by the surgical occlusion of the left main coronary artery. The left ventricular weight increased 8 and 12 weeks after infarction in comparison to that in sham-operated rats. Among the rats with experimental infarction, treatment with E-4177 significantly decreased the left ventricular weight. Although the infarct size was not affected by E-4177, its administration ameliorated the elevated end-diastolic pressure and reduced the systolic pressure. The effects of this agent on the levels of Ang II type 1 (AT1) receptor mRNA and ACe mRNA were evaluated in the non-infarcted myocardium by reverse transcriptase polymerase chain reaction and binding assays. Treatment with E-4177 reduced both the elevated AT1 mRNA and the number of Ang II receptors, but not the ACE mRNA or ACE activity. While the receptor affinity remained unchanged with this agent, the collagen concentration was decreased. On the other hand, the depressed Na+/Ca2+ exchange activity was restored in the non-infarcted myocardium at 8 and 12 weeks after injury to the level seen in the sham-operated rats. These findings suggest that the AT1 receptor antagonist, E-4177, has a beneficial effect on the hemodynamics in spite of the lack of any improvement in the infarct size. These observations may be partly attributed to the prevention of angiotensin II formation during the period of post-infarction healing.

Angiotensin II↗

PubMed1996

Characteristics of fats in Japanese diets and current recommendations.

Although there is no firm evidence to support the "ideal" or even "appropriate" healthy level of dietary fat, the habitual fat consumption pattern in Japan seems to be a criterion for the recommended allowance both in the quantitative and qualitative points of view as judged from the life expectancy and the incidence of degenerative diseases. The new recommended dietary allowance of Japan, fifth revision effective for five years starting in 1995, adopted dietary fat levels of 20-25 energy percent, the ratio of saturated, monounsaturated, and polyunsaturated fatty acids at 1:1.5:1 and the ratio of n-6/n-3 at 4. The recommended fat level is similar to that previously consumed in Japan, and is even lower than that in diets used to treat hyperlipidemia in Western countries, current recommendations in those countries being 30 energy percent fat. Convincing data for the beneficial effects of n-3 polyunsaturated fatty acids on human health, in particular for healthy people, have been presented in only a few reports. However, the recommended n-6/n-3 ratio of 4 seems reasonable compared with the ratio of around 10 in other developed countries. In this context, it is more important to fully understand the nutritional and physiological roles of fat in healthy people rather than in those with chronic disease. At present, the low-fat dietary pattern in Japan appears to be a healthy way of eating.

Dietary Fats↗

PubMed1996

Inhibitory effect of tea polyphenols on histamine and leukotriene B4 release from rat peritoneal exudate cells.

The effect of tea polyphenols on the release of chemical mediators, histamine and leukotriene B4 (LTB4), from rat peritoneal exudate cells (PEC) was studied. Among polyphenols, (-)-epigallocatechin gallate (EGCG) most strongly inhibited the histamine release from the cells stimulated with a calcium ionophore, A23187 or compound 48/80. Though (+)-catechin (C) and (-)-epicatechin (EC) had no effect, (-)-epigallocatechin (EGC) and (-)-epicatechin gallate (ECG) moderately inhibited the histamine release. Similarly, EGCG, ECG, and EGC inhibited LTB4 release from PEC, whereas C and EC were not effective. The magnitude of the inhibitory effect on the release of these mediators of tea polyphenols was in the order of EGCG > ECG > EGC. These results indicated an important role of the triphenol structure in the inhibitory activity. Therefore, the possible antiallergic effect of tea polyphenols can be expected.

Animals↗

PubMed1996

The influence of high and low molecular weight chitosan on colonic cell proliferation and aberrant crypt foci development in CF1 mice.

The effect of dietary chitosan, a fibre of animal origin, on the induction and development of colonic precursor lesions was determined in CF1 mice. Over a 2-wk pretreatment period, one group of mice was given azoxymethane (four injections of 5 mg/kg body weight) and the other was treated with saline. Subsequent to carcinogen or saline pretreatment mice were randomized into one of three dietary groups: (i) control AIN-76 diet; (ii) control AIN-76 diet with 2% low molecular weight chitosan (LMWC); or (iii) control AIN-76 diet with 2% high molecular weight chitosan (HMWC). Mice were maintained on this diet for 6 wk. Mice fed diet containing HMWC had significant reductions in the number of aberrant crypt foci, cell proliferation, crypt height and crypt circumference in the colonic epithelium (P < 0.05). In mice given diet supplemented with LMWC there was a trend towards reduced numbers of aberrant crypts, as well as decreased crypt height and circumference. The results of this study indicate that dietary chitosan reduces the incidence of early preneoplastic markers of colon carcinogenesis, as indicated by aberrant crypts and mitotic figures and altered crypt morphometrics in the murine colon. Molecular range and viscosity of the chitosan may influence the efficacy of this activity.

Animals↗

PubMed1996

Effects of gamma-linolenic acid and its positional isomer pinolenic acid on immune parameters of brown-Norway rats.

Male Brown-Norway rats given purified diets containing safflower oil (SFO, linoleic acid, 18:2 n-6), evening primrose oil (EPO, gamma-linolenic acid, 6,9,12- 18:3 n-6) or Korean pine seed oil (PSO, 5,9,12- 18:3) at the 10% level were immunized twice with intraperitoneal ovalbumin, on days 14 and 35 of the feeding diets, and killed one day after the second booster. The relative population of CD4+ T-lymphocytes in the spleen was significantly lower in rats fed SFO than in those fed EPO or PSO, while that of CD8+ subsets remained unchanged. There was a significant increase in the splenic production of IgG and IgE in the PSO group compared to the SFO group, while EPO significantly increased IgE. The periodical response patterns of the serum levels of IgG and IgE varied depending on the source of dietary fats, and the initial rise of total immunoglobulins tended to be higher in the EPO group. The release by peritoneal exudate cells of histamine was comparable among three groups irrespective of saturation by calcium ionophore A23187, while PSO significantly increased leukotriene B4 production. These observations not only indicate specific roles of gamma-linolenic acid but also diverse influences of different octadecatrienoic acids in various immune measurements.

Animals↗

PubMed1996

Dietary protein modifies oxidized cholesterol-induced alterations of linoleic acid and cholesterol metabolism in rats.

Effects of dietary protein on oxidized cholesterol-induced alterations in linoleic acid and cholesterol metabolism were studied in 4-wk-old male Sprague-Dawley rats, using casein and soybean protein as dietary protein sources. The rats were fed one of the two proteins in cholesterol-free, 0.3% cholesterol or 0.3% oxidized cholesterol mixture diets using a pair-feeding protocol for 3 wk. In the soybean protein-fed group, rats fed oxidized cholesterol did not have lower activity of liver microsomal delta6 desaturase, the rate-limiting enzyme in the metabolism of linoleic acid to arachidonic acid, compared with rats fed cholesterol-free diet, whereas in the casein-fed group the desaturase activity was significantly greater in rats fed oxidized cholesterol than in those fed cholesterol-free diet. This was in contrast to a significant reduction in liver microsomal delta6 desaturase activity by cholesterol, irrespective of protein source. In general, these changes were reflected in the desaturation indices of liver phospholipids. Furthermore, soybean protein significantly increased the fecal excretion of neutral and acidic steroids and tended to reduce (P = 0.082) the accumulation of oxidized cholesterols in the liver. Thus, soybean protein partly modified some of the undesirable effects of oxidized cholesterol through its hypocholesterolemic effect and possibly through the modulation of hepatic delta6 desaturase activity.

Animals↗

PubMed1996

Effect of unsaturated fatty acids and antioxidants on immunoglobulin production by mesenteric lymph node lymphocytes of Sprague-Dawley rats.

The effect of UFA on Ig production by rat MLN lymphocytes was examined to clarify their influence on allergic reactions. A 4-h treatment at 1 mM inhibited the production of IgA, IgG, and IgM by the lymphocytes, but stimulated IgE production. The IgE production-stimulating activity became stronger with increasing number of carbon atoms and/or double bonds. However, no saturated fatty acid with carbon numbers from 12 to 18 affected IgE production by the lymphocytes. Hydrogen peroxide exerted Ig production-regulating activity similar to that of UFA, suggesting that the effect of UFA is at least partly due to oxidation products. Thus, the effect of antioxidants on the Ig production-regulating activity of arachidonic acid was examined. alpha-Tocopherol and BHT annulled the stimulation of IgE production by arachidonic acid, but ascorbic acid was not effective. The IgE production-enhancing activity of UFA was closely related to their oxidation rate in culture medium. These results suggest that UFA enhance the allergic reaction through the stimulation of IgE production and the inhibition of IgA production, and that hydrophobic antioxidants are partially effective to annul the adverse effect of UFA.

Animals↗

PubMed1996

Metabolic interactions between essential and trans-fatty acids.

Trans-fatty acids exacerbate essential fatty acid deficiency in experimental animals by interfering with the metabolism of linoleic (18:2n-6) and alpha-linolenic (18:3n-3) acids and, hence, the eicosanoid production. The interfering effect depends on the type of trans-fatty acid. The detrimental effect of trans-fatty acid, however, apparently disappears when dietary linoleic acid is sufficiently supplemented. Trans-fatty acids appear to disturb fetal growth and birth weight, possibly by the same mechanism.

Animals↗

PubMed1996

Effects of n-3 polyunsaturated fatty acids and lectins on immunoglobulin production by spleen lymphocytes of Sprague-Dawley rats.

We examined the effects of n-3 polyunsaturated fatty acid (PUFA), such as alpha-linolenic (alpha-LA), eicosapentaenoic (EPA), and docosahexaenoic acid (DHA) on immunoglobulin (Ig) production by spleen lymphocytes of Sprague-Dawley rats. n-3 polyunsaturated fatty acid (PUFA) strongly inhibited the production of IgA and IgM and that of IgG weakly at 100 microM. When the lymphocytes were treated with n-3 PUFA in the presence of other inhibitory biomaterials such as lectins, some PUFA attenuated their inhibitory effect on Ig production. In the presence of concanavalin A (ConA), all n-3 PUFA attenuated the inhibitory effect of ConA on the production of IgM or IgG but increased its inhibition of IgA synthesis. Thus, the interaction of n-3 polyunsaturated fatty acid and lectins in spleen interfere with each other or the expression of Ig production regulating activity.

Animals↗

PubMed1996

Cytotoxicity and suppression of immunoglobulin production against human Namalwa cells caused by oxidized cholesterol.

The effects of oxidized cholesterols on proliferation and IgM production of human lymphoblastoid Namalwa cells were examined. An oxidized cholesterol mixture, in contrast to cholesterol, was a potent cytotoxin to Namalwa cells. Among oxidized cholesterols examined, 25-hydroxycholesterol was the most cytotoxic. However, no oxidized cholesterol examined suppressed IgM production, although cholestanetriol and 7-ketocholesterol did suppress it. Thus, oxidized cholesterols are cytotoxic to lymphocytes, while the influence on the immunoglobulin production may be marginal.

Burkitt Lymphoma↗

PubMed1996

Effect of natural food colorings on immunoglobulin production in vitro by rat spleen lymphocytes.

Water-soluble (cacao pigment, cochineal pigment, corn pigment, betanin, carthamus yellow, and monascus pigment) and water-insoluble (gardenia yellow, laccaic acid, bixin, and curcumin) natural colorings inhibited IgE production by rat spleen lymphocytes at 10 and microM, respectively. Although many of these colorings only inhibited the production of IgG and IgM at high concentrations, the water-insoluble colorings enhanced IgM production even at 1 microM. These results suggest that natural colorings have immunoglobulin production-regulating activity.

Animals↗

PubMed1996

Effects of dietary fats and curcumin on IgE-mediated degranulation of intestinal mast cells in brown Norway rats.

Brown Norway rats were primed intraperitoneally with beta-lactoglobulin for 3 wk to induce reaginic antibody, during which time they were fed diets containing 10% each of coconut oil (CO), high oleic safflower oil, safflower oil (SO), or fish oil, then they were challenged for 3 h orally with the antigen. The dietary SO, compared to other dietary fats, resulted in lower circulatory release of rat chymaseII (RChyII), an indicator of degranulation of mucosal mast cells in the intestine, in response to the antigen. Addition of 0.5% curcumin to the CO or SO diet lowered the release. The SO diet, compared to CO diet, tended to increase the concentration of reaginic antibody, but the influence of curcumin addition was not prominent. These results indicate that dietary ingredients differently influence the synthesis of immunoglobulin E and degranulation of mast cells.

Animals↗

PubMed1996

Effect of reaction temperature on the determination of rat serum IgE by the avidin-biotin method.

We established an avidin-biotin method for the sensitive determination of rat IgE and found that a non-specific signal was generated depending on the reaction temperature. When the sera of rats immunized or not with ovalbumin (OVA) were fractionated in a hydroxyapatite column and OVA-specific IgE was determined by the avidin-biotin method at 4 degrees C or 37 degrees C, OVA-specific IgE peaks were detected at 37 degrees C, even with nonimmunized rats, but not at 4 degrees C.

Animals↗

PubMed1996

Effects of fatty acids on accumulation and secretion of histamine in RBL-2H3 cells and leukotriene release from peritoneal exudate cells isolated from Wistar rats.

Effects of fatty acids on accumulation and secretion of histamine in rat basophilic leukemia RBL-2H3 cells and leukotriene release from peritoneal exudate cells isolated from Wistar rats were examined in relation to the manifestation of type I allergic reactions. When RBL-2H3 cells were cultured for 24 h in the presence of 1 mM short chain fatty acids, a marked increase in histamine accumulation was observed, especially with butyric acid. In addition, Ca-ionophore A23187-stimulated histamine release was enhanced in the cells treated with 0.1 mM mono to hexa unsaturated fatty acids with 18 to 22 carbon-chains. On the other hand, LTB4 release from rat peritoneal exudate cells was inhibited in the presence of polyunsaturated fatty acids, both n-6 and n-3, having more than 3 double bonds. Inhibitory activity was enhanced by an increase in the number of double bonds, and docosahexaenoic acid (DHA) exerted the highest activity with complete inhibition at 0.1 mM and 35.5% inhibition even at 10 microM. A hydrophobic radical scavenger (9,10-diphenylanthracene) and two antioxidants (butyrated hydroxytoluene and alpha-tocopherol) inhibited the production of LTB4, but hydrophilic counterparts (mannitol and ascorbic acid) did not. These results suggest that lipophilic anti-oxidative agents, as well as PUFA, inhibit the production of LTB4.

Animals↗