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Biomedical subjects

E Gotoh

Publications and source records attributed to E Gotoh.

At least 37 records · Page 2Linked to original sources
PubMed1998

Effects of renin-angiotensin system blockade and dietary salt intake on left ventricular hypertrophy in Dahl salt-sensitive rats.

We studied the effects of chronic blockade of the renin-angiotensin system on hypertension and cardiac left ventricular hypertrophy (LVH) in Dahl salt-sensitive (DS) rats given a high-salt or low-salt diet. [Experiment 1] Twelve-week-old male DS rats were fed an 8% NaCl diet and received the angiotensin II receptor (AT1) antagonist, candesartan (3 mg/kg/d), the angiotensin converting enzyme inhibitor enalapril (30 mg/kg/d), or vehicle for 6 wk after 3 wk of 8% salt-loading. Neither candesartan nor enalapril with concomitant high salt-loading attenuated the blood pressure (BP) elevation. LVH was also not attenuated significantly by these treatments. [Experiment 2] After 8 wk of 8% salt-loading, the rats were given a 0.3% NaCl diet and concurrently received candesartan, enalapril, or vehicle for 5 wk. Switching from the high-salt to low-salt diet significantly decreased BP and left ventricular mass in the vehicle-treated animals. Both candesartan and enalapril normalized BP during salt-depletion; the blockade of the renin-angiotensin system produced an additive reduction in LVH. These findings suggest that sodium intake and hemodynamic load, but not the renin-angiotensin system, may be major determinants of the development of LVH in DS rats.

Angiotensin II↗
PubMed1997

Percutaneous transluminal mitral valvuloplasty normalizes baroreflex sensitivity and sympathetic activity in patients with mitral stenosis.

BACKGROUND: In patients with mitral stenosis, reduced cardiac output or altered pulmonary hemodynamics may increase sympathetic nerve activity. However, the magnitude of the increase in sympathetic activity in such patients and the effect of valvuloplasty on this activity are unknown. METHODS AND RESULTS: We microneurographically measured muscle sympathetic nerve activity before and after mitral valvuloplasty in 10 patients (mean+/-SEM age, 48+/-2 years) with mitral stenosis and in 10 healthy volunteers (47+/-4 years); hemodynamic variables were also measured. Baroreflex sensitivity was assessed on the basis of the ratio of the change in heart rate or muscle sympathetic activity to the change in mean arterial pressure during intravenous infusion of sodium nitroprusside or phenylephrine. At baseline, muscle sympathetic activity was significantly higher in the patients with mitral stenosis than in the control subjects (42.1+/-3.2 versus 26.1+/-3.7 bursts/min, P<.05). However, there was no significant difference between the groups in sympathetic activity at 1 week after valvuloplasty. The reduction in sympathetic activity after valvuloplasty was maintained for > or = 6 months and correlated with the increase in cardiac index (r=.74, P<.05). Baroreflex sensitivity was significantly lower in the patients than in the control subjects, but after valvuloplasty there was no significant difference in baroreflex sensitivity between the groups. CONCLUSIONS: Sympathetic activity is increased in patients with mitral stenosis. Mitral valvuloplasty in such patients results in early and long-lasting normalization of sympathetic nerve activity, possibly because of an improvement in arterial baroreflex sensitivity.

Adult↗
PubMed1997

A method for detecting sister chromatid exchanges using prematurely condensed chromosomes and immunogold-silver staining.

We have developed a method for detecting sister chromatid exchanges using premature chromosome condensation and immunogold labelling followed by silver enhancement. Cells were grown in bromodeoxyuridine before sister chromatid exchanges were generated with mitomycin C. Calyculin A was then used to condense the chromosomes prematurely. Finally, incorporated bromodeoxyuridine was detected using a gold-conjugated antibody followed by silver enhancement. Exchanged chromatids could easily be seen in the resulting chromosomes. This simple method allows sister chromatid exchanges to be detected with great sensitivity and resolution.

Bromodeoxyuridine↗
PubMed1997

Primary Charnley total hip arthroplasty for congenital dysplasia: effect of improved techniques of cementing.

We performed Charnley total hip arthroplasties on 64 patients (71 hips) between 1976 and 1984 for moderate congenital acetabular dysplasia in which a superolateral cement thickness of less than 20 mm was expected when the cup was placed in the true acetabulum at an angle of 45 degrees. Of these, 59 hips were examined 10 to 17 years after operation; 37 (group A) had been operated on between 1976 and 1982 using Charnley's original technique of cementing the acetabulum and 22 (group B) between 1983 and 1984 using more modern techniques. In group A, aseptic loosening of the socket was observed in ten hips (27.0%) and the 17-year survival rate was 81.5%. In group B, loosening was noted in only one socket (4.5%) and the 13-year survival rate was 100%. The improved techniques produced significantly better long-term results in fixation of the cup in dysplastic hips without bone grafting.

Adult↗
PubMed1997

Valgus-extension osteotomy for advanced osteoarthritis in dysplastic hips. Results at 12 to 18 years.

We treated 31 consecutive patients of mean age 43 years (22 to 59) with severe osteoarthritis of the hip secondary to dysplasia by valgus-extension osteotomy. The clinical results were analysed for factors which may have affected the outcome. The procedure was carried out only on one side and was combined with a Chiari pelvic osteotomy in four patients. The angle of valgus was between 30 and 40 degrees with 10 to 20 degrees of extension. The mean follow-up was 15 years (12 to 18). Clinical evaluation using Charnley's modification of the system of Merle d'Aubigné and Postel showed that the mean score for pain had improved from 2.3 before operation to 4.2 at 15 years, and function from 2.3 to 4.2. Range of movement had decreased from 4.2 to 3.5. Fifteen patients (48.4%) had a pain score of 5 or 6 and were evaluated as satisfactory. Kaplan-Meier survivorship analysis showed a survival rate of 51% at 15 years after operation. Two preoperative factors had a significant positive correlation with the radiological results, namely the thickness of the capital drop osteophyte and the length of the roof osteophyte. We suggest that this procedure is effective for advanced osteoarthritis in the dysplastic hip in young and active patients if these factors are satisfactory on the preoperative radiographs.

Adult↗
PubMed1997

[Telomere DNA and telomerase of lymphoma-derived cell lines--telomere hypothesis for cell growth control].

Telomere is the specialized structure of chromosome end. Telomeric DNA is essential for stabilization of linear double-stranded DNA molecules. Human telomeric DNA comprises the tandem repeat (AATGGG)n. Telomeres of normal somatic cells shorten progressively on every cell division, and telomere length is considered to determine cellular proliferative capacity. Most normal cells except germ line cells lack telomerase activity. Evidence of telomerase reactivation in human cancer cells was reported in 1994. The telomere hypothesis of aging and cell immortalization has drawn much attention in recent years. We examined telomere DNA and telomerase activity of Burkitt's lymphoma cell lines and EBV-infected proliferating B lymphocytes. All of these cells had varied average size of TRFs and the cell lines of lymphoma origin showed elevated telomerase activity.

Burkitt Lymphoma↗
PubMed1996

Detection and evaluation of chromosomal aberrations induced by high doses of gamma-irradiation using immunogold-silver painting of prematurely condensed chromosomes.

We developed a method for detecting chromosomal aberrations after irradiation with high doses of gamma-rays. At high dose levels, few of the irradiated cells are able to enter mitosis so that it is difficult to obtain enough mitotic chromosomes using a conventional colcemid block. Therefore, okadaic acid was used to condense prematurely the chromosomes of interphase cells. Even after irradiation with doses > 40 Gy, okadaic acid was able to force sufficient numbers of cells to condense their chromosomes. Segments of chromosomes were then detected by chromosome painting using a gold-conjugated antibody followed by silver enhancement. This simple method allows highly damaged chromosomes to be detected with great sensitivity.

Cell Cycle↗
PubMed1996

AT1 receptor antagonist, TCV 116, does not prevent cardiac hypertrophy in salt-loaded Dahl salt-sensitive rats.

1. We investigated the effects of direct blockade of angiotensin II (AngII) by a potent, non-peptide angiotensin II toff 1 (AT1) receptor antagonist, TCV 116, on the development of cardiac hypertrophy in salt-loaded Dahl salt-sensitive rats. 2. Six week old male Dahl salt-sensitive rats (n = 44) were fed a 4% salt diet and were simultaneously given various doses of TCV 116 orally for 7 weeks. Each control group received vehicle alone. 3. Dietary high salt intake elevated blood pressure continuously and caused left ventricular hypertrophy in rats treated with vehicle. TCV 116 had a minor effect on the rise in blood pressure. Left ventricular mass (left ventricular weight/body-weight) decreased slightly but not significantly, in rats treated with 3 mg/kg per day of TCV 116 (n = 8). Higher doses of TCV 116 (6 and 10 mg/kg per day; n = 8 each) did not show a decrease in left ventricular mass compared with the vehicle control. 4. These results suggest that AngII blockade has only minor effects on hypertension and on cardiac hypertrophy in salt-loaded Dahl salt-sensitive rats and that the renin-angiotensin system may not contribute to the development of cardiac hypertrophy in Dahl salt-sensitive rats on a moderately high-salt diet.

Angiotensin Receptor Antagonists↗
PubMed1996

A case report of angioedema during long-term (66 months) angiotensin converting enzyme inhibition therapy with enalapril.

We describe a rare case of ACE inhibitor-induced angioedema during long-term therapy in a 51-year-old male patient with essential hypertension; and this is the third case reported of this adverse reaction in Japan. The patient received enalapril for 66 months, and complained of a dry cough which was mild and tolerable. Recently, he noted tenderness of his mouth, face, swelling of lips and tongue for 3 to 4 h after taking his morning dose of enalapril. These symptoms abated spontaneously, so he continued taking the drugs. He again noted similar episodes of angioedema 29 days after the first experience. He had no further episodes of angioedema or dry cough after cessation of enalapril. This case of angioedema developed during long-term therapy with enalapril administered as 19,930 mg of enalapril maleate. We emphasize that angioedema may occur at any time during the use of enalapril.

Angioedema↗
PubMed1995

Assignment of a human autoimmune antigen, p80-coilin gene to chromosome 17q21-q23 and of its possible pseudogene to chromosome 14.

In order to determine the chromosomal locations of an autoimmune antigen, the coilin gene and its pseudogene, we amplified the segments of the two genes by the polymerase chain reaction (PCR) and screened a panel of somatic cell hybrids for the presence of the gene products. The results indicate that the human coilin gene and its pseudogene can be assigned to chromosome 17 and chromosome 14, respectively. Further analysis of cell hybrids bearing chromosome 17 with various deletions localized the coilin gene to the region q21-q23.

Animals↗
PubMed1994

Effects of hypertension and aging on fibronectin expression in aorta of Dahl salt-sensitive rats.

Effects of hypertension and aging on aortic fibronectin expression were investigated in male Dahl salt-sensitive (Dahl-S) and salt-resistant (Dahl-R) rats fed either a low- or high-salt diet from 5 to 37 wk of age. In comparison to low-salt controls, the steady-state mRNA levels for aortic fibronectin in salt-loaded Dahl-S rats were dramatically increased at 37 wk of age, corresponding to a severe stage of hypertension with high mortality, whereas at earlier ages representing early to established phases of hypertension, no significant changes were observed. Salt loading affected neither blood pressure nor aortic fibronectin expression in Dahl-R rats. Aging without coexisting hypertension did not cause significant changes in aortic fibronectin mRNA levels all through the study period in either strain of rats. These results suggest that aortic fibronectin may be strongly regulated by factors associated with severe hypertensive organ damages caused by long-standing hypertension in salt-loaded Dahl-S rats. Also suggested was that aortic fibronectin may not play a major role in the pathogenesis of early aortic changes occurring in response to hypertension or as a process of aging.

Aging↗
PubMed1994

Pharmacokinetics and pharmacodynamics of the alpha 1-adrenergic antagonist bunazosin retard in hypertensives.

The pharmacokinetics and pharmacodynamics of an alpha 1-blocker a sustained release formulation of bunazosin (Detantol R, E1015, 4-amino-2-(4-butyrylhexahydro-1H-1,4-diazepin-1-yl)-6,7- dimethoxyquinazoline hydrochloride, CAS 52712-76-2), were investigated in hypertensive patients with normal renal function (NRF) and those with impaired renal function (IRF). The subjects were hospitalized and placed on a constant sodium diet (NaCl 7 g/day) throughout the study. A 6 mg dose of bunazosin was administered orally once a day for 8 days. Measurement of blood pressure (BP) and sampling of blood and urine specimens were made on the first and last days of treatment. A significant decrease in both systolic and diastolic BP was observed after consecutive dosing of bunazosin compared to baseline values over 24 h in the NRF and for 8 h in the IRF. There were no significant differences in plasma profiles of bunazosin in both groups after single and consecutive dosing. The pharmakokinetic parameters of bunazosin in the NRF and IRF groups did not differ after the single and the consecutive dosing, except for plasma peak levels (Cmax) which were significantly higher in the IRF than those in the NRF. There were, however, neither prolongation of apparent elimination half-life (t1/2), nor increase in Cmax, nor area under the plasma concentration-time curve (AUC0-24) after consecutive dosing in both groups. Cumulative urinary excretion rates of bunazosin were less than 1.1% of dose in both groups, and those did not differ significantly between the NRF and IRF groups in both single and consecutive studies.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-1 Receptor Antagonists↗
PubMed1994

Effect of an angiotensin receptor antagonist, TCV-116, on sympathetic nerve activity in patients with essential hypertension.

The effects of an angiotensin II receptor (AT1) antagonist on sympathetic nervous responses to a mental arithmetic task and a cold pressor test were investigated using a placebo-controlled, single-blind design in 8 patients with essential hypertension (53 +/- 3 years). All patients received a placebo for 2 weeks (placebo run-in period), after which the control group (P; n = 4) continued to receive the placebo, while the experimental group (TCV; n = 4) received TCV-116 at 4 mg/day for 4 weeks (treatment period). After basal measurements were carried out, an arithmetic task and a cold pressor test were conducted on the last day of each period. Blood pressure (BP), heart rate (HR) and electrocardiogram (ECG) were continuously monitored. Muscle sympathetic nerve activity (MSNA) was assessed by determining the burst rate of the mean voltage neurogram obtained from the tibial nerve. Sympathovagal balance was also assessed, by determining the area ratio of the low frequency (LF: 0.05-0.15 Hz) to high frequency bands (HF: 0.16-0.5 Hz) of a power spectral analysis of HR variability (maximum entropy method). During the placebo run-in period, there were no significant differences in basal BP, HR, LF/HF or MSNA between the two groups. During the treatment period, basal mean BP in the TCV group was significantly lower (p < 0.05) than that in the P group, but there were no significant differences in basal HR, LF/HF or MSNA between the two groups. Although the arithmetic stress significantly increased BP, HR and LF/HF in both groups, MSNA was not significantly altered in either group.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin Receptor Antagonists↗
PubMed1994

Long-term therapy with terazosin may improve glucose and lipid metabolism in hypertensives: a multicenter prospective study.

The effects of long-term monotherapy with terazosin, an alpha-1 blocker, on blood pressure, glucose tolerance, and serum lipid profiles were prospectively investigated in 53 hypertensive patients: 19 with normal glucose tolerance (NGT) and 34 with impaired glucose tolerance (IGT). The plasma glucose, serum lipids, fructosamine, and glycosylated hemoglobin A1c (HbA1c) levels were determined before and during long-term (6 months) therapy with terazosin. A 75-g oral glucose tolerance test was performed before and during long-term terazosin therapy. Significant falls in both systolic and diastolic blood pressure in both patient groups were maintained during the long-term therapy with terazosin. Neither fasting nor postglucose-load venous plasma glucose levels were altered in either group of patients, and diabetes mellitus did not develop in any patient with NGT during the study. There was no significant change in the insulinogenic index (delta IRI/delta BS at 30 minutes after glucose load) in either patient group. In patients with IGT, glucose intolerance was slightly improved with significant reductions in HbA1c and fructosamine during terazosin therapy. Serum total cholesterol (TC) and triglyceride levels were significantly decreased in patients with IGT. In addition, TC and low density lipoprotein (LDL) cholesterol were significantly decreased in patients with hypercholesterolemia (TC > 220 mg/dL). These results suggest that long-term therapy with terazosin may improve glucose and lipid metabolism in hypertensive patients and terazosin seems to be an antihypertensive agent with beneficial effects for hypertensive patients with either dyslipidemia or impaired glucose metabolism.

Adrenergic alpha-Antagonists↗