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H Rakugi

Publications and source records attributed to H Rakugi.

At least 19 recordsLinked to original sources
PubMed2006

Roles of TGF-beta1 and apoptosis in the progression of glomerulosclerosis in human IgA nephropathy.

Apoptotic glomerular cells have been detected in the severely damaged glomeruli that are a consequence of human IgA nephropathy. Transforming growth factor-(TGF) beta1 is known to induce apoptosis in cultured mesangial cells. To clarify whether TGF-beta1 contributes to the progression of IgA nephropathy by activating apoptosis in glomerular cells, we examined the expression of TGF-beta1 gene and apoptotic changes in kidney biopsy samples, and assessed those relations to the severity of nephropathy. 32 patients with IgA nephropathy, showing proteinuria (> 1 g/day) and serum creatinine less than 1.5 mg/dl were classified according to glomerular sclerosis index (GSI) into 3 groups (Group I: GSI < 0.3,Group 11: 0.3 < or = GSI < 1.0, Group: III GSI > or = 1.0). Computer-aided morphometry of glomeruli and arteries, and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling of fragmented DNA (TUNEL) staining were performed. Expression of TGF-beta1 and caspase-3 mRNAs in renal biopsy samples was analyzed by real-time PCR (Taq Man method). Increased glomerular area, interstitial fibrosis, lymphocytic infiltration, and tubulointerstitial changes were observed to accompany increased severity of GSI. TUNEL index was higher in Group III. The levels of TGF-beta1 and caspase-3 mRNAs were significantly increased in Group III (183 and 190%, respectively). Furthermore, caspase-3 mRNA levels were tightly associated with TGF-beta1 mRNA expression (r = 0.677, p < 0.0001). The present study suggests that the activation of TGF-beta1 plays a role in the progression of IgA nephropathy even in the moderate degree of glomerular injury, in part via activation of apoptosis of glomerular cells.

Adult↗
PubMed2004

Hypertension in a patient with Gitelman's syndrome.

Gitelman's syndrome is an autosomal recessive disorder characterized by sodium wasting and hypotension. A middle-aged woman was diagnosed with Gitelman's syndrome because of typical clinical manifestations in the youth and homozygous mutations of 18-base-pair insertion in exon 6 of thiazide-sensitive NaCl-cotransporter gene. It was unusual that she showed hypertension with advancing age. Her serum potassium levels remained low at around 3.5 mEq/l despite potassium supplementation. This case demonstrates that hypertension could result in spite of the extremely decreased sodium reabsorption in Gitelman's syndrome and that essential hypertension is genetically heterogeneous, and abnormality of all genes may not be necessarily required to cause blood pressure rise.

Adult↗
PubMed2001

Additive effects of nicorandil on coronary blood flow during continuous administration of nitroglycerin.

OBJECTIVES: We examined whether patients with ischemic heart disease (IHD) should be treated with nicorandil, an adenosine triphosphate-sensitive potassium channel opener, in addition to the regular use of nitrates. BACKGROUND: It has been reported that nicorandil possibly has additive effects on nitroglycerin (NTG) treatment for angina, but the mechanism is not clear. METHODS: We directly measured anterograde coronary blood flow (CBF) with a Doppler guide wire to examine the effects of intravenous administration of NTG (0.3 mg) and nicorandil (6 mg) during continuous administration of NTG at a sufficient dose (25 microg/min) in subjects with normal and stenotic coronary arteries. RESULTS: Additional systemic administration of NTG decreased anterograde CBF (normal -19.7%; stenotic -21.2%). In contrast, nicorandil increased anterograde CBF in both normal (54.6%) and stenotic (89.6%) coronary arteries, without the coronary steal phenomenon. There was a tendency toward nicorandil-dilated diameters in the patients with stenotic arteries (p = 0.06). There were no effects of additional administration on pulmonary artery wedge pressure. There was no difference in changes in heart rate and mean aortic blood pressure between NTG and nicorandil therapy. CONCLUSIONS: These results suggest that in patients treated with nitrates, additional administration of nicorandil is more useful, in terms of increasing CBF, than additional administration of nitrates. Adjunctive use of nicorandil with nitrates may provide the further benefit of myocardial protection and may improve the prognosis of patients with IHD.

Aged↗
PubMed2001

A common mutation of low-density lipoprotein receptor gene is associated with essential hypertension among Japanese.

Candidate genes offer one approach to the identification of the genetic susceptibility to hypertension. A common gene variant of the low-density lipoprotein (LDL) receptor gene (LDLR) that affects plasma LDL metabolism within the normolipidaemic range, may be such a candidate gene. A common mutation of LDLR, C1773T, was associated with lipid metabolism such that the T1773 allele increased plasma LDL levels in a Caucasian population. The present study examined whether C1773T/LDLR was associated with essential hypertension in a Japanese population. Subjects with essential hypertension (EHT, n = 300) with a family history of hypertension, and controls (NT, n = 310, sex- and age-matched with EHT) were recruited from among out-patients at Osaka University Hospital. A C1773T substitution at codon 570 in LDLR was determined using PCR-Hinc II-RFLP. It was revealed that the C1773 allele was significantly more frequent (0.89) among hypertensive patients (chi2 = 9.58, P < 0.01) than normotensives (0.83), the calculated odds ratio being 1.7 (95% CI: 1.2-2.4). The effect of the T1773 allele on increasing cholesterol was significant in normotensives without antihyperlipidaemic medication, but not in hypertensives. After adjustments of confounding factors, the estimated odds ratio for hypertension in the subjects with C1773 homozygote increased to 2.1 (95% CI: 1.3-3.5), suggesting that this polymorphism is an independent risk factor for hypertension. Our results show that the C1773 mutant of LDLR increases susceptibility to hypertension, but not via hypercholesterolaemia.

Asian People↗
PubMed2001

Lack of correlation between Mbo I restriction fragment length polymorphism of renin gene and essential hypertension in Japanese.

Predisposition to essential hypertension is associated with gene polymorphisms of the renin angiotensin system (RAS). Gene polymorphisms of the angiotensinogen and angiotensin converting enzyme genes are known to be risk factors for hypertension, while few studies concerning the renin gene polymorphism have been published. In the present investigation, we carried out a case control study using a Japanese population to examine the genetic influence of the renin gene on the predisposition to hypertension. Patients (n=235) recruited from outpatients at Osaka University Hospital and diagnosed with essential hypertension or receiving long-term antihypertensive medication participated in the study. Normotensive control subjects (n=510) without a history of hypertension and without diabetes mellitus were recruited from the same population, and were sex-matched with experimental subjects. A polymorphism in intron 9 of the human renin gene was determined as the Mbo I restriction fragment length polymorphism (Mbo I-RFLP). There was no significant association between Mbo I-RFLP of the renin gene and predisposition to essential hypertension in Japanese (p>0.05, chi2=2.1). These results suggest that the Mbo I (+) allele of the renin gene does not increase the risk for hypertension in Japanese.

Aged↗
PubMed2001

Effects of antihypertensive drugs and gene variants in the renin-angiotensin system.

Many genes and environmental factors are involved in the pathogenesis of hypertension, but the exact cause of essential hypertension has not yet been clarified. Gene polymorphism of the renin-angiotensin system (RAS) is one of the candidates. In the current study, we examined whether there was a correlation between the gene polymorphisms in RAS and either the choice of antihypertensive drugs or their efficacy. Subjects with essential hypertension (n=299) were recruited from among the outpatients of Osaka University Hospital and provided their informed consent for genetic analysis. Physicians freely chose the antihypertensive drugs and adjusted its dose until the patient's blood pressure was well controlled. The efficacy of each antihypertensive drug was estimated using the following formula: ABP=BP 1 (before treatment) - BP 2 (after treatment)/BP 1 x 100 (%). Gene variants in RAS were determined using PCR or PCR-RFLP (restriction fragment of polymorphism). The gene polymorphisms of RAS were not associated with delta SBP or ADBP. However, the mean ASBP in subjects with a deletion homozygote of the angiotensin converting enzyme gene (ACE/DD) was significantly lower (p<0.05) than that in patients with an insertion I allele of the ACE gene. The gene polymorphisms of RAS did not significantly affect the choice of antihypertensive drugs. Even though gene polymorphism in the renin angiotensin system was not a major factor in the antihypertensive therapy, the determination of genotype might be of help in the management of essential hypertension.

Antihypertensive Agents↗
PubMed2001

[A case of severe systemic edema in an elderly hypertensive patient with systemic lupus erythematodes during long-term treatment with anti-hypertensive drugs].

A 71-year-old woman receiving both angiotensin II receptor antagonist and calcium antagonist suffered severe systemic edema. She had been treated for essential hypertension with amlodipine for 2 years and candesartan for 3 months, and systemic lupus erythematodes (SLE) with steroids. During treatment, severe systemic edema appeared, mainly on her face, arms, and legs. At first, we suspected drug-induced edema by candesartan, so it was halted, but the edema still continued. We then considered amlodipine to be the culprit, and finally, the severe systemic edema disappeared after cessation of amlodipine. To control her blood pressure, we recommended candesartan, but 3 months late she suffered severe systemic edema again, thus the causative we drugs of her edema were thought to be both amlodipine and candesartan. Edema is a common symptom in elderly patients and we frequently observe drug-induced edema. In this case, there was underlying acceleration of blood vessel permeability induced by SLE and steroids and moreover, vasodilatation by candesartan and/or amlodipine further accelerated blood vessel permeability, and thus might have caused severe edema. It is very difficult to determine the cause of edema, especially in elderly patients, but we should consider not only one but also two or more drugs as being involved in drug-induced edema.

Aged↗
PubMed2001

[Review of randomized trials of angiotensin receptor blockers in the treatment of patients with congestive heart failure].

Angiotensin-converting enzyme (ACE) inhibitors are the first-line drugs for the treatment of congestive heart failure, but many patients could not receive those benefits because of intolerance. Recent randomized trials of angiotensin receptor blockers (ARB) in the treatment of patients with congestive heart failure elucidated clinical benefits of ARB as well as ACE inhibitors. ELITE II showed equivalent effect on mortality and morbidity between losartan and captopril and less adverse events in losartan. Val-HeFT showed additive benefits of valsartan on standard treatment with ACE inhibitors, diuretics and digitalis in patients with heart failure. CHARM would be elucidate the clinical usefulness of candesartan cilexetil in a broad spectrum of patients with symptomatic heart failure including patients whose LVEF greater than 40%.

Angiotensin Receptor Antagonists↗
PubMed2000

Quantitative ultrasonic tissue characterization can identify high-risk atherosclerotic alteration in human carotid arteries.

BACKGROUND: Recently, ultrasonic tissue characterization of the composition of plaques has been performed in a quantitative fashion on the basis of integrated backscatter (IBS) analysis, but most of those studies have used high-frequency ultrasound to obtain microscopic images. METHODS AND RESULTS: We performed B-mode measurement and IBS signal analysis with acoustic densitometry with a 7.5-MHz linear-array transducer in freshly excised human aortas (n=58) (normal, atheromatous, and fibrous tissue) obtained at autopsy. Atheromatous and fibrous tissue had a similar intima-media thickness (IMT), but the IBS value in atheromatous specimens was lower than that in fibrous specimens. We further applied this method to human carotid ultrasonography. The subjects were young (80 regions), middle aged with 1 or no coronary risk factors (low risk) (120 regions), middle aged with >/=2 coronary risk factors (high risk) (240 regions), or elderly (80 regions) or were patients with myocardial infarction (MI) with multivessel disease (90 regions). The IMT was similar in middle-aged, elderly, and MI subjects. In contrast, the IBS value was significantly higher in elderly subjects and lower in high-risk middle-aged and MI subjects compared with that in low-risk middle-aged subjects. The percent of regions diagnosed as atheromatous (IBS less than mean minus 2-SD value of IBS in young subjects) was 11% in low-risk middle-aged subjects, 29% in high-risk middle-aged subjects, and 63% in the MI group. CONCLUSIONS: In conjunction with conventional B-mode imaging, IBS analysis with carotid ultrasonography appeared to provide prognostic information to identify a high-risk group with systemic atherosclerosis, which could lead to coronary heart disease in individuals with early-stage disease.

Adult↗
PubMed2000

Deletion polymorphism of angiotensin-converting enzyme gene is associated with postprandial hyperglycaemia in individuals undergoing general check-up.

1. Deletion polymorphism, DD, of the angiotensin-converting enzyme (ACE) gene is reported to be related to cardiovascular disease, which is frequently based on insulin resistance. 2. To clarify the relationship between the ACE genotype DD and plasma glucose increases after an oral glucose load, we performed 75 g oral glucose tolerance test (OGTT) in 301 nondiabetic men (age range 30-60 years) undergoing general check-up. 3. Insertion/deletion (I/D) polymorphism of the ACE gene was explored using a polymerase chain reaction. The frequency of the II, ID and DD genotypes was 0.43, 0.43 and 0.14, respectively. 4. There were no differences in baseline clinical characteristics between subjects with each ACE genotype. 5. The mean (+/- SEM) plasma glucose level at 60 min of the OGTT was significantly higher in subjects with the DD genotype (170.8 +/- 6.9 mg/dL) than in subjects with either the II or ID genotype (mean value for two groups 156.6 +/- 2.7 mg/dL; P < 0.05). Moreover, the mean percentage change of plasma glucose after 60 min of the OGTT, a marker of plasma glucose increase, was significantly higher in individuals with the DD genotype than in individuals with either the II or ID genotypes. 6. In contrast, the mean fasting plasma glucose level, the plasma glucose level at 120 min, the glucose response area and the fasting insulin level were not different between individuals with the DD genotype and individuals with other genotypes. 7. In conclusion, subjects with the DD genotype showed transiently higher levels of plasma glucose after an oral glucose load than subjects with other genotypes. Further studies are required to determine whether the association between ACE genotype and postprandial hyperglycaemia influences the incidence of cardiovascular disease and diabetes mellitus.

Adult↗
PubMed2000

Association of polymorphism in the promoter region of the apolipoprotein E gene with diastolic blood pressure in normotensive Japanese.

The epsilon4 allele of apolipoprotein E (APOE) is reported to be a genetic risk factor of atherosclerosis through hyperlipidemia and late-onset Alzheimer's dementia. A recent report showed that a genetic variant (A -491T) in the promoter region of the APOE gene increases the risk of Alzheimer's disease. In the present study, we examined whether these APOE polymorphisms were genetically involved in essential hypertension. Japanese hypertensives (n=180) with a family history of hypertension and normotensive controls (n=195, sex and age matched with hypertensives) were recruited from the outpatients of Osaka University Hospital, and an informed consent to participate in the study was obtained from each person. APOE polymorphisms were determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The frequencies of the A -491 allele in hypertensives and normotensives were 0.98 and 0.97, respectively, and the TT/-491 genotype was not found in either group. No significant differences between hypertensives and normotensives were observed in allele frequencies in either APOE polymorphism; however, the mean diastolic blood pressure in normotensive subjects with AA/-491 was significantly higher than in the subjects with AT/-491 (p < 0.01). These results suggest that the presence of the APOE promoter polymorphism is not a major risk factor for hypertension but that it does have some minor effect on basal blood pressure variation.

Adult↗
PubMed2000

[Clinical implications of ultrasonic tissue characterization for atherosclerotic carotid intima-media].

Current imaging modalities, such as ultrasonic tissue characterization, have enabled accurate determination of the composition of atherosclerotic plaque of excised aortic tissue. The aim of this study is to compare integrated backscatter (IBS) echo signals of the intima-media complex of human carotid arteries between young and elderly subjects, and to evaluate the ability of ultrasonic tissue characterization. We compared the difference in ultrasonic parameters between the carotid arteries of young healthy subjects (n = 27, 25 +/- 1 y.o.) and elderly subjects (n = 55, 75 +/- 4 y.o.). Intima-media thickness (IMT) and calibrated IBS value (C-IBS: Tissue IBS-vessel lumen IBS value) were measured. The IMT values of young and elderly subjects were 0.54 +/- 0.03 and 1.08 +/- 0.07 mm, respectively (p < 0.01). C-IBS of elderly subjects (11.7 +/- 0.8 dB) was significantly higher than that of young subjects (6.9 +/- 0.7 dB). Significantly wider standard deviation of C-IBS value in each individual was observed in elderly subjects (mean +/- SE of individual standard deviation in C-IBS: 4.2 +/- 0.9 dB) compared with that in young subjects (1.7 +/- 0.3 dB). This might reflect varied composition of atherosclerotic plaques in elderly subjects. IBS analysis would become a promising method to distinguish plaque composition quantitatively and to assess the stability of plaques in clinical setting.

Adult↗
PubMed1999

Deletion polymorphism in the gene for angiotensin-converting enzyme is not a risk factor predisposing to abdominal aortic aneurysm.

OBJECTIVE: to establish whether deletion of the angiotensin-converting enzyme (ACE) gene is a risk factor predisposing to abdominal aortic aneurysm (AAA) or not. METHODS: the study included 125 patients with AAA and 153 controls randomly selected from 328 individuals. The control subjects were confirmed not to have an AAA, but matched with the AAA group for age, sex, hypertension, diabetes mellitus, and hyperlipidaemia. The presence of ACE polymorphism was detected by a polymerase chain reaction using DNA extracted from blood. RESULTS: the distribution of ACE genotypes and allele frequencies in the control and AAA groups was not significantly different. CONCLUSION: the deletion polymorphism in the ACE gene is not a risk factor for AAA.

Aged↗
PubMed1999

Upregulation of renin-angiotensin system during differentiation of monocytes to macrophages.

BACKGROUND: We have demonstrated that accumulated macrophages in human coronary arteries strongly express angiotensin converting enzyme in accordance with the development of atheromatous plaques. However, there are few reports on the regulation of the renin-angiotensin system in macrophages and in monocytes as their source. OBJECTIVE: To examine whether the renin-angiotensin system is upregulated during the differentiation of monocytes to macrophages, and whether it is further regulated by angiotensin II and cytokines. MATERIALS AND METHODS: We used a human leukemia cell line, THP-1, for monocytes. Differentiated THP-1, induced by adding phorbol 12-myristate 13-acetate for 24 h, were used as macrophages. Expression of messenger RNA of the renin-angiotensin system components was measured by quantitative reverse-transcriptase polymerase chain reaction. Angiotensin converting enzyme activity and subtype-specific angiotensin-binding sites of cultured cells, and angiotensin II production in the culture medium were measured. RESULTS: Macrophages expressed all components of the renin-angiotensin system except chymase. Cellular angiotensin converting enzyme activity and angiotensin II in the medium were increased 3.2- and 4.5-fold during differentiation, respectively. Expression of angiotensin II type 1 (AT1) and type 2 (AT2) receptors was increased 6.2-and 6.4-fold during differentiation, and was sustained for 7 days. Incubation with angiotensin II for 24 h caused downregulation of both AT1 and AT2 receptor messenger RNA, but the expression levels were still more than threefold higher compared with monocytes. The density of binding sites of AT1 and AT2 receptors in macrophages was 0.26 +/- 0.02 and 0.15 +/- 0.01 fmol/10(6) cells, respectively. CONCLUSION: The renin-angiotensin system is markedly activated during monocyte/macrophage differentiation, and may participate in the development of atherosclerosis.

Angiotensin II↗
PubMed1999

Relative localization of angiotensin-converting enzyme, chymase and angiotensin II in human coronary atherosclerotic lesions.

BACKGROUND: Studies using cell cultures and animal models have indicated an important role for angiotensin II in atherosclerosis. In humans, at least two major enzymes are involved in the conversion of angiotensin I to angiotensin II: so-called angiotensin-converting enzyme (ACE) and chymase. Enhanced activation of chymase in atherosclerotic tissue homogenates has been reported in animal models, but its contribution to the generation of angiotensin II has not been studied. OBJECTIVE: To clarify the localization of chymase and its pathophysiologic role in the formation of angiotensin II, using human coronary arteries. DESIGN AND METHODS: Twenty-four coronary artery segments obtained from 14 autopsied patients were characterized histologically into the following categories: normal coronary arteries with diffuse intimal thickening, hypercellular lesions, atheromatous plaques and fibrosclerotic plaques. We compared the cellular localization of chymase, ACE and angiotensin II expression using immunocytochemical techniques. RESULTS: Chymase was expressed only in the cytosole of mast cells in all segments. On the basis of the histologic study, the number of chymase-positive cells in the intima of atheromatous plaques was significantly higher than that in normal coronary arteries with diffuse intimal thickening. The expression of angiotensin II in the intima was enhanced in hypercellular lesions and atheromatous plaques. Localization of angiotensin II in the intima was associated with that of ACE. Immunodouble staining did not show colocalization of angiotensin II and chymase. CONCLUSIONS: These results suggest an important role for the production of angiotensin II by ACE in the progression of atherosclerosis in human coronary arteries. Enhanced expression of chymase appears not to be involved in angiotensin II production in the intima.

Adolescent↗