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Biomedical subjects

H Akita

Publications and source records attributed to H Akita.

At least 37 records · Page 2Linked to original sources
PubMed2001

Decreased longevity in Japanese men, associated with low-molecular-weight apolipoprotein(a) phenotypes.

Lipoprotein(a) [Lp(a)] is an established risk factor for atherosclerosis. High plasma Lp(a) concentrations are associated with low-molecular-weight (LMW) apolipoprotein(a) (apo a) phenotypes, which raises the question of whether LMW apo a phenotypes occur less frequently in the elderly. To assess this possibility, we studied apo A phenotype and allele frequencies in Japanese subjects > or = 80 years old (men:women = 40:34) in comparison with those <80 years old (men:women = 221:296). Significantly fewer LMW phenotypes and LMW alleles were observed in > or = 80 year old men compared with those < 80 years old: 2.5% versus 16.1% for the LMW phenotype frequency and 1.3% versus 9.7% for the LMW allele frequency (P<0.05, Fisher's exact probability test). Similar differences were not found in the women. Consistent with this, plasma Lp(a) concentrations were significantly lower in the men > or = 80 years old than in the younger group. These results indicate that LMW apo a phenotypes are associated with a shorter lifespan in men but not in women, possibly reflecting the higher susceptibility of men to atherosclerosis.

Adult↗
PubMed2001

Metabolic changes in human CD36 deficiency displayed by glucose loading.

Previous in vitro studies have shown that CD36 participates in cellular fatty acid (FA) uptake. In vivo evidence for a physiologic role of CD36 in this process is poor and mostly obtained in animals. To examine the metabolic role of human CD36, we performed a glucose loading test for normals (n = 16) and subjects with CD36 deficiency, both Type I (n = 5) and Type II (n = 16). After 30 min, FA levels had fallen by 60.1% in normals but by only 31.7% in Type II deficiency (P <0.01 vs. normals) and 16.5% in Type I deficiency which remained significantly higher than the other two groups out to 2 h. Further, changes in triglyceride and glucose metabolism were observed in the both types of CD36 deficiency. Impaired fast FA clearance by muscle and consequently increased hepatic FA uptake seem to underlie these changes. We conclude that human CD36 deficiency causes systemic metabolic changes.

Adult↗
PubMed2001

[Critical role for cell cycle regulators in androgen receptor function].

Androgen plays an important role in the growth of prostate cancer, but the molecular mechanism that underlies development of resistance to antiandrogen therapy remains unknown. Cyclin E has now been shown to increase the transactivation activity of the human androgen receptor (AR) in the presence of its ligand dihydrotestosterone. The enhancement of AR activity by cyclin E was resistant to inhibition by the antiandrogen 5-hydroxyflutamide. Cyclin E was shown to bind directly to the AB domain of the AR, and to enhance its AF-1 transactivation function. These results suggest that cyclin E functions as a coactivator of the AR, and that aberrant expression of cyclin E in tumors may contribute persistent activation of AR function, even during androgen ablation therapy.

Antineoplastic Agents, Hormonal↗
PubMed2001

[The efficacy of a comprehensive smoking cessation class, combined with nicotine patch and gum replacement therapy].

A six-month comprehensive smoking cessation class was conducted in our hospital, and the results were evaluated after one year. To increase the rate of smoking cessation, a smoking cessation support team composed of a medical doctor, a pharmacist, nurses, a registered dietitian, and a physical therapist was formed. The team provided specialized lectures and comprehensive group counseling programs every two weeks for the first two months and every month for the next four months. Each participant's expired carbon monoxide concentration and body weight were measured at every attendance. The participant continued with beneficial behavioral treatment for smoking cessation for six months, with nicotine replacement therapy (NRT) for the first eight weeks. The protocol of our NRT consisted of both the routine use of nicotine patches (Nicotinell TTS) and the rescue use of nicotine gum (Nicorette). We first ascertained each participant's degree of nicotine dependence, using the Fagerström Tolerance Questionnaire score, and daily nicotine intake was estimated by a detailed questionnaire. We then divided the participants into two NRT groups according to their nicotine dependence. The higher nicotine dependence group consisted of those whose Fagerström Tolerance Questionnaire score was more than 5 points or whose estimated nicotine intake was more than 10 mg/day. This group they used Nicotinell TTS 30 (TTS 30) for the first four weeks, TTS 20 for the next two weeks, and TTS 10 for the last two. In the lower dependence group. TTS 20 and TTS 10 were each given for four weeks. Nicotine gum use was restricted to 4 pieces a day for the first week and reduced by one per day each subsequent week. As a result, there was an 81.3% smoking cessation rate after eight weeks, 70.3% after six months, and 58.2% after one year. In conclusion, two courses of routine nicotine patch use, with the addition of restricted rescue use of nicotine gum, can produce better longterm abstinence results than previously reported NRTs, suggesting that this may be one of the best ways to cease smoking. We also emphasize that intensive group counseling programs and lectures supported by doctors and medical teams, as well as a continuing behavioral treatment component, may be indispensable for enhancing longterm sustained abstinence rates.

Administration, Cutaneous↗
PubMed2000

Human CD36 deficiency is associated with elevation in low-density lipoprotein-cholesterol.

To find out whether CD36 plays a role in the human lipoprotein metabolism, we studied lipoprotein profiles in subjects with CD36 deficiency. Apparently healthy Japanese volunteers (n = 790) were classified by flow cytometry into three groups of normal (platelet and monocyte CD36+, n = 741, 93.8%), type-II deficiency (platelet CD36- and monocyte CD36+, n = 45, 5.7%), and type-I deficiency (platelet and monocyte CD36-, n = 4, 0.5%). At least one of reported mutations in the CD36 gene was found in all four subjects with type-I deficiency and in 23 of the 45 subjects with type II. Among 779 subjects (731 normals, 44 type II, and four type I) with serum triglyceride levels of <400 mg/dL, serum total cholesterol and low-density lipoprotein (LDL) cholesterol were significantly elevated in type-II deficiency (P = 0.0095 and 0.0382 versus normal, respectively, Scheffe's F-test), while differences were not significant in triglyceride and high-density lipoprotein-cholesterol. Similar tendency was observed in type-I deficiency, although the differences were not statistically significant because of small sample size. We conclude that CD36 deficiency elevates LDL cholesterol, indicating a contribution of CD36 to LDL metabolism.

CD36 Antigens↗
PubMed2000

Induction of KAI-1 expression in metastatic cancer cells by phorbol esters.

KAI-1 is a tumor suppressor gene whose down-regulation has been shown to be associated with the development of metastases of cancer cells. Here, we demonstrated that KAI-1 expression was induced by activating protein kinase C even in metastatic prostate cancer cell lines in which its expression was significantly down-regulated. KAI-1 expression was enhanced in a dose-dependent manner by PMA, and its induction is at least in part due to transcriptional activation. Pretreatment with calphostin C abrogated its induction by PMA. Our findings may provide useful information for developing a novel drug capable of inducing KAI-1 expression and thereby inhibiting metastasis.

Antigens, CD↗
PubMed2000

Resistance to endotoxin shock in transgenic mice overexpressing endothelial nitric oxide synthase.

BACKGROUND: Nitric oxide (NO) plays a central role in the pathogenesis of septic shock. However, the role of the NO produced by endothelial NO synthase (eNOS) in septic shock is still unclear. We examined the effect of chronic eNOS overexpression and the role of eNOS-derived NO in lipopolysaccharide (LPS)-induced septic shock using eNOS transgenic (Tg) mice. METHODS AND RESULTS: LPS was intraperitoneally injected into Tg and control mice. No differences existed in the peak plasma nitrate and nitrate levels induced by LPS between the 2 genotypes. In LPS-treated control mice, blood pressure progressively declined and reached 60% of basal levels (from 97+/-3 to 59+/-3 mm Hg) 24 hours after LPS injection. In contrast, the blood pressure of LPS-treated Tg mice fell only 15% from basal levels (from 84+/-4 to 71+/-4 mm Hg) after the first 6 hours and, thereafter, it remained at this level. LPS-induced increases in the expression of the mRNA of both vascular cell adhesion molecule-1 and intracellular adhesion molecule-1 in the lungs were significantly lower in Tg mice than in control mice. LPS-induced pulmonary leukocyte infiltration and increases in lung water content were also significantly attenuated in Tg mice. Histological examination revealed that lung injury after LPS injection was milder in Tg mice. Furthermore, Tg mice exhibited enhanced survival from LPS-induced septic shock compared with control mice. CONCLUSIONS: Chronic eNOS overexpression in the endothelium of mice resulted in resistance to LPS-induced hypotension, lung injury, and death. These effects are associated with the reduced vascular reactivity to NO and the reduced anti-inflammatory effects of NO.

Animals↗
PubMed2000

(R)-ACX is a novel sufonylurea compound with potent, quick and short-lasting hypoglycemic activity.

We investigated the mechanism of the hypoglycemic effect of (R)-4-(1-acetoxyethyl)-N-(cyclohexylcarbamoyl)benzene-sulfonamide [(R)-acetoxyhexamide; (R)-ACX], a new sulfonylurea compound. (R)-ACX potently stimulated the release of insulin from cultured pancreatic beta-cells (HIT T15 cells), established from hamster islet cells SV40-transformed. When (R)-ACX was orally administered to fasted rats, it decreased the plasma glucose level in a dose-dependent manner. The hypoglycemic effect of (R)-ACX was quick and short lasting, as compared to that of acetohexamide and glibenclamide. The quick and short-lasting hypoglycemic effect of (R)-ACX was thought likely to result from rapid absorption of (R)-ACX and rapid elimination of (R)-ACX and its metabolite, (R)-hydroxyhexamide. Furthermore, (R)-ACX was found to suppress the increase of blood glucose level due to starch loading in fasted mice. (R)-ACX may be useful in the control of postprandial hyperglycemia to patients with non-insulin-dependent diabetic mellitus.

Acetohexamide↗
PubMed2000

T102C polymorphism of the serotonin (5-HT) 2A receptor gene in patients with non-fatal acute myocardial infarction.

Serotonin (5-HT), released from activated platelets, has been implicated in the pathogenesis of acute myocardial infarction (AMI). 5-HT induces platelet aggregation and vascular contraction through 5-HT2A receptor activation at sites of coronary atherosclerosis, leading to thrombus formation. Recently, a 5-HT2A receptor gene T102C polymorphism has been reported to be associated with clinical response to 5-HT2A receptor antagonist in patients with schizophrenia, suggesting this polymorphism of the gene affects the 5-HT2A receptor function. To investigate the relationship between the T102C polymorphism and AMI, we conducted a case-control study of 255 non-fatal AMI patients and 255 control subjects. Among the patients, the prevalence of TT genotype was significantly higher than in controls (32.5 vs. 24.3%; P<0.05). In male patients (n=216), the prevalence was much higher than in control subjects (33.8 vs. 24. 1%, P<0.03). In multiple logistic regression models, odds ratio of TT genotype was 1.45 (95% CI 0.96-2.20) in all and 1.61 (95% CI 1. 03-2.53) (P<0.05) in males. The association of T102C polymorphism of the 5-HT2A receptor gene with non-fatal AMI was statistically significant and independent of other risk factors in males. The TT genotype of the 5-HT2A receptor gene may enhance susceptibility to AMI. Our observations suggest that the T102C polymorphism of the 5-HT2A receptor gene can serve as a new genetic marker for AMI.

Aged↗
PubMed2000

Inhibition of endothelium-dependent arterial relaxation by oxidized phosphatidylcholine.

Formation of oxidized phosphatidylcholine (ox-PC), oxidatively fragmented phosphatidylcholine (PC) containing a short-chain and/or polar oxidative residue at the sn-2 position, in the process of LDL oxidation as well as its existence in atherosclerotic lesions has been demonstrated. To clarify the pathophysiological role of ox-PC in the vascular reactivity, we investigated the effects of various ox-PCs on the isometric tensions in rabbit thoracic aortas. Ox-PCs, which were produced upon oxidation of sn-2 polyunsaturated fatty acid (PUFA)-containing PCs, dose-dependently inhibited endothelium-dependent relaxation (EDR) evoked by acetylcholine or substance P. On the other hand, neither native PUFA-containing PCs nor an oxidative product of monounsaturated fatty acid-containing PC showed an inhibitory effect. None of ox-PCs affected endothelium-independent relaxation to nitroglycerin. The PC-headgroup fraction, but not the oxidized fatty acids fraction, was responsible for the inhibition of EDR by ox-PC. EDR was reduced by 2-(5-oxovaleroyl)-PC, one of the secondary oxidative products of PCs that contains a short chain aldehydic residue at the sn-2 position, but not by PC hydroperoxide, the primary oxidative product. Although the possibility could not be completely ruled out that lysophosphatidylcholine rather than ox-PC may be responsible for inhibitory effects on EDR, these results suggest a novel vascular activity of ox-PCs generated from sn-2 PUFA-containing PCs which may be implicated in the pathophysiology of vascular tone.

Acetylcholine↗
PubMed2000

Carvedilol improves endothelium-dependent dilatation in patients with coronary artery disease.

OBJECTIVE: Flow-mediated, endothelium-dependent dilatation (FMD) of the coronary and peripheral circulation is impaired by increased oxidative stress in patients with coronary artery disease (CAD). Carvedilol is a novel beta-blocker that also shows an antioxidant effect in vitro. However, the effect of carvedilol on endothelial dysfunction associated with established coronary atherosclerosis has not been examined in the clinical setting. METHODS: We studied 29 patients with CAD, including 17 with recent myocardial infarction and 12 with stable effort angina pectoris. Nineteen patients received carvedilol (10 with infarction and 9 with angina), and 10 were treated with placebo (7 with infarction and 3 with angina). We also studied 13 age- and sex-matched control subjects. Brachial FMD during reactive hyperemia and nitroglycerin-induced, endothelium-independent dilatation were assessed by high-resolution ultrasound. RESULTS: FMD was smaller in patients with CAD compared with controls, although nitroglycerin-induced dilatation was similar. Carvedilol significantly improved FMD after long-term treatment (5. 1% +/- 0.4% at baseline to 7.8% +/- 0.3% after 4 months; P <.01) but not after short-term treatment (5.1% +/- 0.4% at baseline to 5.0% +/- 0.7% after 2 hours). Placebo therapy had no effect on endothelial dysfunction. Neither carvedilol nor placebo had an effect on nitroglycerin-induced dilatation after short- and long-term treatment. Long-term carvedilol therapy also significantly decreased the plasma level of thiobarbituric acid-reactive substances compared with placebo (carvedilol, 5.8 +/- 0.4 nmol/mL to 4.6 +/- 0.3 nmol/mL, P <.01; placebo, 5.9 +/- 0.4 nmol/mL to 5.8 +/- 0.4 nmol/mL, P = not significant). CONCLUSION: These findings suggest that the improvement of endothelial function by carvedilol may be caused by its antioxidant activity.

Adrenergic beta-Antagonists↗
PubMed2000

[Comparison of the morphology and the reactivity of Chlamydia pneumoniae isolated in north-Kanto Area, Ibaraki Prefecture, Japan].

To compare the morphology among Chlamydia pneumoniae (C. pneumoniae), strain TW183 and strains which were isolated in the area of Kasumigaura, Ibaraki from 1992 to 1995. C. pneumoniae were infected on HL cell monolayers and cultured in 5% CO2 at 35.5 degrees C for about 60 hrs. The cells were harvested and fixed with 2.5% glutaraldehyde, and then the regular procedure for observation of Chlamydia in inclusion by transmission electron microscope was performed. Immunoblot assay was carried out by using highly and partially purified C. pneumoniae TW183 and 4 isolates with partial purification as antigens. The results were as follows: the shape of TW183 and the isolates included pear and round shapes, respectively. Immunoblotting profiles were the same in terms of band-formation patterns with the serum from a patient infected with C. pneumoniae. These results may indicate that the round shape of C. pneumoniae elementary body (EB) is predominantly pandemic in Japan, although pear-shaped EBs of C. pneumoniae were found in the neighboring prefecture of Chiba.

Child↗
PubMed2000

Cystic lymphangioma of retroperitoneum and groin.

We report a case of cystic lymphangioma of the retroperitoneum and groin. A 38-year-old male was referred to our hospital due to a right inguinal mass without tenderness. CT, MRI revealed retroperitoneal mass and inguinal mass. Biopsy of the inguinal mass was performed. The lesion was multicystic, and adherent to the surrounding tissue. Pathological examination revealed lymphangioma.

Adult↗
PubMed2000

Mechanisms of reduced nitric oxide/cGMP-mediated vasorelaxation in transgenic mice overexpressing endothelial nitric oxide synthase.

NO, constitutively produced by endothelial NO synthase (eNOS), plays a key regulatory role in vascular wall homeostasis. We generated transgenic (Tg) mice overexpressing eNOS in the endothelium and reported the presence of reduced NO-elicited relaxation. The purpose of this study was to clarify mechanisms of the reduced response to NO-mediated vasodilators in eNOS-Tg mice. Thoracic aortas of Tg and control mice were surgically isolated for vasomotor studies. Relaxations to acetylcholine and sodium nitroprusside were significantly reduced in Tg vessels compared with control vessels. Relaxations to atrial natriuretic peptide and 8-bromo-cGMP were also significantly reduced in Tg vessels. Reduced relaxations to these agents were restored by chronic N(G)-nitro-L-arginine methyl ester treatment. Basal cGMP levels of aortas were higher in Tg mice than in control mice, whereas soluble guanylate cyclase (sGC) activity in Tg vessels was approximately 50% of the activity in control vessels. Moreover, cGMP-dependent protein kinase (PKG) protein levels and PKG enzyme activity were decreased in Tg vessels. These observations indicate that chronic overexpression of eNOS in the endothelium resulted in resistance to the NO/cGMP-mediated vasodilators and that at least 2 distinct mechanisms might be involved: one is reduced sGC activity, and the other is a decrease in PKG protein levels. We reported for the first time that increased NO release from the endothelium reduces sGC and PKG activity in mice. These data may provide a new insight into the mechanisms of nitrate tolerance and cross tolerance to nitrovasodilators.

Animals↗
PubMed2000

Synthesis of decalin type chiral synthons based on enzymatic function.

Enzymatic monobenzoylation of (+/-)-2-hydroxy-decahydro-5,5,8a-trimethyl-1-naphthalenemethano l derivatives (1-4) using vinyl benzoate in organic solvent gave the optically active diols (1-4) and monobenzoates (16-19). The enantiomeric excess (ee) of the enzymatic reaction products were found to be in the range of 11% to 49%. On the other hand, enzymatic hydrolysis of the acetoxybenzylidene acetal (+/-)-25d, e was found to give more than 90% ee of (10aS)-25d, e in moderate yield. Finally, the 90% ee of (10aS)-25e was converted to the 90% ee of the desired (8aS)-1.

Enzymes↗