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Biomedical subjects

K Shimamoto

Publications and source records attributed to K Shimamoto.

At least 235 records · Page 13Linked to original sources

[Therapeutic policy for elderly hypertensives in Japan--a questionnaire survey of specialists].

In order to clarify the therapeutic policy for hypertension in the elderly, we mailed a questionnaire to 147 specialists in Japan and received 123 replies. The upper age limit for antihypertensive treatment was considered to be 80-85 years old by about 50% of the specialists, but the other 50% did not consider an upper age limit. The range of the systolic blood pressure (BP) for which drug treatment was indicated in those without cardiovascular complications was considered to be increased with age, being 160 mmHg and higher in those aged 60-69, 160-170 mmHg and higher in those aged 70-79, and 170-180 mmHg and higher in those aged 80-89, while the level of diastolic BP requiring treatment was considered to be 90-95 mmHg and higher in all age ranges. The goal of BP control was considered to be less than 150/90 mmHg in those aged 60-69, and less than 160/90 mmHg in those aged 70-79 by the majority of the specialists, and to be higher in those aged 80-90, i.e. less than 170-180/95-100 mmHg by more than 20% of the specialists. As the initial selection of antihypertensive regimen, calcium antagonists followed by angiotensin I-converting enzyme inhibitors (ACEI) were selected by the majority, while diuretics, beta-blockers and alpha 1 blockers were chosen by the minority.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

[Characteristics of blood pressure regulating endocrinological factors in elderly essential hypertensives].

Plasma renin activity (PRA) was lower in elderly normotensive subjects and essential hypertensives (EHT), and a significant negative correlation was found between PRA and age in both groups. In EHT, the proportion of the low renin group to total EHT increased with aging. There was a significantly positive correlation between plasma norepinephrine (PNE) and age in NT, but not in EHT. The mean value of PNE in young subjects was significantly higher in EHT than in NT, but not in the middle-aged and elderly groups, suggesting the important role of PNE in young EHT. Power spectral analysis revealed a significant reduction of both sympathetic and parasympathetic activity with aging in NT and EHT, indicating much caution may be required if sympathetic nerve activity is evaluated only by PNE levels in elderly EHT. The expanded plasma volume was another characteristic in elderly EHT, and suppressed activity of renal kallikrein-kinin, prostaglandin and dopamine may be involved with its mechanisms. Regarding insulin sensitivity in elderly EHT, it was shown that 1) the reduction of insulin sensitivity plays some role in age related acceleration of hypertension and glucose intolerance, 2) selective insulin resistance with respect to glucose metabolism already exists at lower ages in EHT, and 3) both Na retention and pressor system activation via insulin action might be a cause of blood pressure elevation in EHT.

Adult↗

The natriuretic mechanisms of neutral endopeptidase inhibitor in rats.

The activity of the renal kallikrein-kinin system is controlled by the concentration of intrarenal kinins. Neutral endopeptidase 24.11 (NEP) cleaves kinins as effectively as kininase I and kininase II. It is also well known that NEP metabolizes atrial natriuretic peptide (ANP). The present study evaluated the effects of NEP inhibitor on renal action by kinins, ANP and nitric oxide in Sprague-Dawley normotensive rats and DOCA-salt hypertensive rats. In normotensive rats, we demonstrated that 1) inhibition of NEP potentiates the contribution of kinins to the renal water-sodium metabolism and overcomes the contribution of ANP to that metabolism, 2) nitric oxide participates in the action of kinins, and 3) changes in urinary cGMP excretion do not reflect the changes in plasma ANP, but the changes in nitric oxide, under these conditions. On the other hand, it was also suggested that augmented ANP may contribute mainly to renal water-sodium handling by NEP inhibitor in DOCA-salt rats. Therefore, the contributions of the two systems to the diuretic and natriuretic mechanisms of NEP inhibition may differ between Sprague-Dawley normotensive rats and DOCA-salt hypertensive rats.

Animals↗

Kinin generation by hemodialysis membranes as a possible cause of anaphylactoid reactions.

1. Severe anaphylactoid reactions have been reported in some patients treated with angiotensin converting enzyme (ACE) inhibitors during hemodialysis with a polyacrylonitrile (PAN) membrane. Generation of bradykinin via contact activation at the negatively charged membrane surface and reduced bradykinin breakdown due to ACE inhibition have been suggested as possible causes. This hypothesis was evaluated in the present study. 2. PAN or cellulose dialyzer membranes were incubated with plasma at different concentrations of ACE inhibitor. The rate and extent of kinin accumulation was dependent on the ACE inhibitor concentration. 3. Bradykinin levels were determined in "historical" plasma samples drawn from patients treated with ACE inhibitor at the onset of anaphylactoid reactions during hemodialysis with PAN dialyzers. The kinin levels were significantly higher (2.4 +/- 0.05 pmol/ml) than in samples from a group of control patients (0.29 +/- 0.02 pmol/ml). 4. Plasma kinin levels were measured in patients who developed anaphylactoid reactions during dialysis with a PAN membrane though not being treated with ACE inhibitor. At the onset of the reaction, kinin levels increased to 2.1 pmol/ml in the line entering the dialyzer and to 10.5 pmol/ml in the line leaving the dialyzer compared to not more than 0.12 pmol/ml upon dialysis with other membranes. 5. These in vitro and in vivo results demonstrate that contact of blood with a polyacrylonitrile membrane leads to the generation of kinins which accumulate if ACE is inhibited. It is very likely that kinin accumulation in the circulation is the cause of anaphylactoid reactions during hemodialysis with PAN membranes in patients treated with ACE inhibitors and, in some cases, in patients not receiving ACE inhibitor medication.

Acrylic Resins↗

Does insulin resistance participate in an impaired glucose tolerance in primary aldosteronism?

It has been reported that glucose intolerance is occasionally found in primary aldosteronism. In this study, we measured insulin sensitivity by the euglycaemic hyperinsulinaemic glucose clamp technique and ability to release insulin by 75 g oral glucose tolerance test (OGTT) in primary aldosteronism. Seven patients with primary aldosteronism (PA) (53.7 +/- 3.4 years; mean +/- SEM) and eight normotensive subjects (NS) (57.5 +/- 2.6 years) were employed in this study. The two-hour euglycemic hyperinsulinaemic glucose clamp technique was performed in seven PA before adrenalectomy, six PA after adrenalectomy and eight NS. The 75 g OGTT was also done in five PA before and after adrenalectomy and eight NS. The mean rate of glucose infusion to maintain euglycemia for the last 30 minutes of the clamp technique was used as an indicator of insulin sensitivity (M-value). The total blood glucose levels during 75 g OGTT (area under the curves) (sigma blood glucose) were significantly higher in PA than those in NS, and the total insulin levels during 75 g OGTT (area under the curves) (sigma IRI) were significantly lower in PA than those in NS. After adrenalectomy in PA, blood glucose levels were significantly decreased and IRI were significantly increased compared with the normal range. There was a significant positive correlation (P < 0.05, r = 0.71) between serum potassium levels and IRI in PA which were determined before and after adrenalectomy. In PA, M-values (240.7 +/- 14.6 mg/m2/min) were significantly higher than those in NS (199.0 +/- 12.3 mg/m2/min).(ABSTRACT TRUNCATED AT 250 WORDS)

Female↗

Effects of an angiotensin II receptor antagonist, TCV-116, on insulin sensitivity in fructose-fed rats.

This study was designed to examine the effects of an angiotensin II receptor antagonist on insulin sensitivity in an insulin-resistant hypertensive rat model (fructose-fed rats; FFR). Male Sprague-Dawley rats were fed a fructose-rich diet or standard chow for 4 weeks and then treated with either 1 mg/kg/day of TCV-116 (angiotensin II receptor antagonist) or vehicle for a further 2 weeks. Steady-state plasma glucose (SSPG) was measured while the animals were conscious. Insulin (2.5 mU/kg/min) and glucose (8 mg/kg/min) were simultaneously infused to determine insulin sensitivity in each group. The mean arterial pressure (MAP) was higher in the FFR (133 +/- 5 mmHg) than in the control group (120 +/- 3), and TCV-116 (110 +/- 4) decreased MAP significantly. SSPG was also higher in the FFR group (207 +/- 6 mg/dl) than in the control (137 +/- 10, p < 0.01), and TCV-116 (171 +/- 7) significantly reduced SSPG. The FFR group also had higher steady-state plasma insulin (SSPI) levels than the control (107 +/- 10 microU/ml for FFR and 63 +/- 12 for control, p < 0.05), and TCV-116 attenuated the increase in SSPI (73 +/- 11, p < 0.05). Thus, the angiotensin II receptor antagonist improved insulin resistance, as assessed by determining SSPG in FFR, suggesting that angiotensin II antagonism may play an important role in improving of insulin resistance in FFR.

Angiotensin Receptor Antagonists↗

Renal kallikrein-kinin, prostaglandin E2, and dopamine systems in young normotensive subjects with a family history of essential hypertension.

Before dopamine infusion, there were no differences in urinary excretion of sodium (UNaV), fractional excretion of sodium (FENa), kinin and kallikrein quantity (KALQ), activity (A) or specific activity (Sp) between the young normotensive subjects with (FH[+]) and without a family history of essential hypertension (FH[-]), whereas urinary dopamine excretion was significantly lower and urine volume (UV) and urinary prostaglandin E2 (PGE2) were significantly higher in FH(+) subjects than in FH(-) subjects. After infusion of dopamine (3 micrograms/kg/min for 60 min), the increases in UV, UNaV, FENa, kinin, KALA, KALSp, and PGE2 were higher in FH(+) than in FH(-) subjects. From these results, it was concluded that (1) the augmented response of urinary kallikrein-kinin and PGE2 to infused dopamine in FH(+) subjects could be explained by the hereditary suppression of dopamine in the kidneys, and (2) the maintenance of a normal level of the basal kallikrein-kinin system and an increase of PGE2 in FH(+) subjects may be caused by compensatory mechanisms other than that of renal dopamine.

Adult↗

Exercise-induced STV1 elevation: a sign of right ventricular dysfunction in recent inferior myocardial infarction.

BACKGROUND: Little is known about exercise-induced electrocardiographic ST segment shift in right-sided precordial leads, especially elevated ST in patients with subacute inferior myocardial infarction. OBJECTIVE: To test the clinical significance of exercise-induced STV1 deviation with special regard to right ventricular function and right ventricular involvement. DESIGN: Sixty-eight patients with recent inferior myocardial infarction (without having a left descending arterial lesion) aged 30 to 73 years (mean +/- SD, 59.1 +/- 10.0) were investigated with respect to biventricular function observed in radionuclide ventriculography and treadmill stress electrocardiographic findings. RESULT: STV1 shift during exercise (delta STV1) had a negative linear logarithmic relationship only with the right ventricular ejection fraction (RVEF) and no correlation with the left ventricular ejection fraction (delta STV1 = 6.7604-1.7528xlnRVEF, r = 0.709, P = 0.0001). Significant STV1 elevation (delta STV1 of 0.5 mm or more) predicted right ventricular dysfunction (RVEF of 40% or less) and right ventricular infarction with sensitivities of 76% and 77%, specificities of 88% and 92%, and accuracies of 84% and 77%, respectively. Twenty patients with STV1 elevation (0.5 mm or more) showed nearly identical rest and exercise electrocardiographic findings, exercise capacities and similar stenotic lesions on coronary angiography, to 43 patients without significant STV1 elevation. Elective balloon angioplasty reduced the delta STV1 during exercise in only three of six patients (50%) with right ventricular infarction. CONCLUSION: Exercise-induced STV1 elevation may be a useful indicator of global right ventricular dysfunction and/or right ventricular infarction in the subacute phase of myocardial inferior infarction.

Adult↗

[The role of endogenous digitalis-like factor on hypertensive mechanisms in reduced renal mass hypertensive rats].

The pathophysiological role of endogenous digitalis-like factor (EDLF) on blood pressure elevation was studied in reduced renal mass (RRM) rats with saline loading for a model of volume dependent hypertension. Fifty-four male Sprague-Dawley rats were operated on to remove varying proportions of their kidney mass (3/6RRM, n = 12; 4/6RRM, n = 16; 5/6RRM, n = 13) or sham operated (control, n = 13). They were given 1% NaCl to drink for 4 weeks. Urinary EDLF (UDLF) excretions were measured by radioimmunoassay using the anti-digoxin antibody, and urine volume, urinary sodium excretion and blood pressure were recorded. Systolic blood pressure was elevated significantly at the 1st week in 5/6RRM rats (from 135 +/- 3 mmHg to 157 +/- 3 mmHg) and continued to increase gradually until the 4th week (186 +/- 8 mmHg), but this was not seen in the other three groups. Urine volume and urinary sodium excretion increased after 1% saline drinking in all groups. UDLF increased significantly at the 1st day after 1% saline drinking in all groups (control: from 2.3 +/- 0.3 to 3.8 +/- 0.2, 3/6RRM: from 2.8 +/- 0.2 to 5.0 +/- 0.2, 4/6RRM: from 3.6 +/- 0.3 to 6.9 +/- 0.4, 5/6RRM: from 3.6 +/- 0.2 to 7.6 +/- 0.6 ng.digoxin/kg/day) but returned to the basal levels 2 days later in controls (3.0 +/- 0.4 ng.digoxin/kg/day) and 2 weeks later in 3/6RRM rats (3.1 +/- 0.2 ng.digoxin/kg/day) and 4/6RRM (3.3 +/- 0.3 ng.digoxin/kg/day). UDLF only remained higher than the basal level in 5/6RRM rats (2nd week: 4.7 +/- 0.4, 3rd week: 5.7 +/- 0.7, 4th week: 5.9 +/- 0.8 ng.digoxin/kg/day). A significant positive correlation was found between UDLF and systolic blood pressure (r = 0.278, p < 0.05), and between UDLF and sodium excretion (r = 0.657, p < 0.001) in 5/6RRM rats. When daily UDLF was measured in all groups during the 1st week, the integrated UDLF for 7 days of 1% saline consumption in 5/6RRM rats was significantly higher than in controls and 3/6RRM rats, and tended to be higher than in 4/6RRM rats. Integrated UDLF correlated positively with systolic blood pressure or changes in the systolic blood pressure. From these observations, it was concluded that EDLF might induce sodium excretion and that EDLF has an important role in the pathogenesis of blood pressure elevation in 5/6RRM rats.

Animals↗

Salt and hypertension: water-sodium handling in essential hypertension.

This paper describes sodium handling in the kidney and the significance and mechanisms of its effects upon essential hypertension. In patients with low renin essential hypertension, plasma and urinary norepinephrine levels, plasma renin activity and fractional excretion of sodium were significantly lower, while plasma volume, extracellular fluid volume and exchangeable sodium were higher than in normal renin essential hypertension. The suppression of some renal depressor-natriuretic systems, the dopaminergic, kallikrein-kinin and prostaglandin E2 systems may contribute to the retention of sodium-water in these patients, because these depressor systems were observed to be greatly suppressed in essential hypertension, especially in the low renin group. The reduction of conversion from L-dopa to dopamine by dopa-decarboxylase in the proximal tubules was suggested from our clearance studies as the mechanism of the suppression of renal dopaminergic activity. Moreover, renal dopaminergic activity was already suppressed at the prehypertensive stage, possibly through the inhibition of renal dopa-decarboxylase activity. Thus, it appears that the suppression of renal depressor-natriuretic systems play an important role in the pathogenesis of essential hypertension through the retention of sodium and body fluid volume.

Body Water↗

Processing followed by complete editing of an altered mitochondrial atp6 RNA restores fertility of cytoplasmic male sterile rice.

Two atp6 genes were found in the mitochondrial genome of cytoplasmic male sterile (CMS) rice carrying the [cms-bo] cytoplasm. One (N-atp6) was identical to the normal cytoplasmic gene, while the second (B-atp6) was identified as a candidate CMS gene by Southern analysis of the mitochondrial genome of CMS cybrid rice. The coding sequence of B-atp6 was identical to the normal N-atp6 gene but its 3'-flanking sequence was different starting at 49 bases downstream from the stop codon. Northern analysis showed that B-atp6 is transcribed into a 2.0 kb RNA in the absence of the Rf-1 gene, whereas two discontinuous RNAs, of approximately 1.5 and 0.45 kb, were detected in the presence of the Rf-1 gene. Determination of the 3' and 5' ends of these RNAs suggested that the two discontinuous RNAs were generated from the 2.0 kb RNA by RNA processing at sites within the B-atp6-specific sequences by the action of the Rf-1 gene. Sequence analysis of cDNA clones derived from the N-atp6 RNA and the processed and unprocessed RNAs of B-atp6 indicated that the processed B-atp6 RNAs were edited as efficiently as the N-atp6, whereas unedited and partially edited RNAs were detected among unprocessed RNAs. RNA processing by Rf-1 thus influences the sequential post-transcriptional editing of the B-atp6 RNAs. Because the unprocessed RNAs of B-atp6 are possibly translated into altered polypeptides, our results suggest that interaction of RNA processing and editing plays a role in controlling CMS expression and the restoration of fertility in rice.

Amino Acid Sequence↗

Proximal promoter region of the wheat histone H3 gene confers S phase-specific gene expression in transformed rice cells.

The cis-regulatory elements that confer cell cycle-dependent expression to the wheat histone H3 gene were investigated in rice cells (Oc strain) transformed with H3/GUS chimeric genes. 5' deletion mutants of the H3 promoter region (from -1711, -908 or -185 to +57 relative to the transcription start site) were joined to the coding sequence of the bacterial beta-glucuronidase (GUS) gene then introduced stably into rice cells. S1 analyses of the RNA from transformed rice cells whose cell cycles had been synchronized by treatment with aphidicolin showed that the steady-state levels of the transcripts from chimeric genes were altered with the change in DNA synthesis and the content of rice H3 mRNA throughout the cell cycle. Even though H3 promoter activity decreased as 5' deletion proceeded, transcripts from the chimeric genes showed increases, as much as 10-fold 1 h after release from the aphidicolin block, which were rapidly lost over the next 4 h. The results suggest that the 242 bp sequence from -185 to +57, which contains the basal promoter region, confers the S phase-specific expression of the H3 gene and that the upstream sequence from position -186 is required for the full activity of this promoter.

Base Sequence↗

Trans-activation and stable integration of the maize transposable element Ds cotransfected with the Ac transposase gene in transgenic rice plants.

To develop an efficient gene tagging system in rice, a plasmid was constructed carrying a non-autonomous maize Ds element in the untranslated leader sequence of a hygromycin B resistance gene fused with the 35S promoter of cauliflower mosaic virus. This plasmid was cotransfected by electroporation into rice protoplasts together with a plasmid containing the maize Ac transposase gene transcribed from the 35S promoter. Five lines of evidence obtained from the analyses of hygromycin B-resistant calli, regenerated plants and their progeny showed that the introduced Ds was trans-activated by the Ac transposase gene in rice. (1) Cotransfection of the two plasmids is necessary for generation of hygromycin B resistant transformants. (2) Ds excision sites are detected by Southern blot hybridization. (3) Characteristic sequence alterations are found at Ds excision sites. (4) Newly integrated Ds is detected in the rice genome. (5) Generation of 8 bp target duplications is observed at the Ds integration sites on the rice chromosomes. Our results also show that Ds can be trans-activated by the transiently expressed Ac transposase at early stages of protoplast culture and integrated stably into the rice genome, while the cotransfected Ac transposase gene is not integrated. Segregation data from such a transgenic rice plant carrying no Ac transposase gene showed that four Ds copies were stably integrated into three different chromosomes, one of which also contained the functional hph gene restored by Ds excision. The results indicate that a dispersed distribution of Ds throughout genomes not bearing the active Ac transposase gene can be achieved by simultaneous transfection with Ds and the Ac transposase gene.

Base Sequence↗

Plasma noradrenaline as an indicator of functional state in hearts with mitral stenosis: the influence of acutely reduced left atrial pressure by balloon mitral commissurotomy.

To investigate the mechanism in which plasma noradrenaline concentration (pNA) is elevated in heart failure, the effect of balloon mitral valvuloplasty was used as a model of acute manipulation of the left atrial pressure reduction in ten patients with mitral stenosis. Gorlin mitral valve area and pNA were correlated with New York Heart Association functional class and found to have a significant exponential inverse relationship with each other ([pNA, pg/ml] = 198.9 x [mitral valve area, cm2]-0.696; P = 0.003). Elevated pNA could be partially explained by a reduced cardiac index (CI) ([pNA, pg/ml] = 403.4 x [CI, l/min/m2]-0.889; P = 0.027; r = 0.495), especially in severely failed hearts, but not by pulmonary capillary wedge pressure (PCWP). However, the percent changes (% delta) of variables early after balloon valvuloplasty exhibited a paradoxical contrast; % delta pNA showing a clear negative exponential correlation with % delta PCWP ([% delta pNA] = 436.0 x [% delta PCWP + 80]-0.679 - 80; P = 0.021), but not with % delta CI. These results suggest that pNA should be considered an indicator of cardiac functional class in mitral stenosis. PNA is modulated by both cardiac index and pulmonary capillary pressure, but in different ways.

Adult↗

Efficacy and mode of action of manidipine: a new calcium antagonist.

Clinical studies were performed on patients with mild-to-moderate essential hypertension to elucidate the efficacy and mode of action of manidipine. Augmentation of diuresis and natriuresis during the short- and long-term phases of manidipine treatment was found in essential hypertensive patients. Manidipine partly inhibited sympathetic nerve activity and suppressed the mean arterial pressure response to infused norepinephrine. This drug also inhibited aldosterone secretion. Natriuresis and suppression of pressor responses may contribute to the depressor mechanisms of this drug. After manidipine administration, increases in both urinary calcium and uric acid were observed. Both parameters were positively correlated with urinary excretion of sodium, and the inhibition of tubular reabsorption may contribute to this mechanism. The increase in plasma parathyroid hormone may also be involved in the calciuresis produced by manidipine. Patients with lower plasma renin activity or lower plasma ionized calcium levels showed a greater reduction in blood pressure after manidipine administration. Thus the hypotensive action of manidipine was more pronounced in low renin essential hypertension.

Adult↗

Antihypertensive effect of a newly synthesized endothelin antagonist, BQ-123, in a genetic hypertensive model.

A newly synthesized ET(A)-selective antagonist, BQ-123, was examined with respect to its anti-endothelin(ET) action in vitro and in vivo and its effect on blood pressure in Wistar Kyoto rats (WKY), spontaneously hypertensive rats (SHR) and stroke-prone spontaneously hypertensive rats (SHRSP). In isolated porcine coronary arteries, BQ-123 (0.07 microM to 6.0 microM) shifted the concentration-response curve for ET-1 to the right without affecting the maximal response of ET-1, its pA2 value being 7.35. Intravenous infusion of BQ-123 at a rate of 1.2 and 30 mg/kg/hr produced a significant decrease in blood pressure in 20- to 29-week-old SHRSP, but did not alter blood pressure in 13- to 16-week-old WKY or in 18- to 19-week-old and 40-week-old SHR. The hypotensive effect of BQ-123 depended on the pretreatment blood pressure level. These results suggest that ET-1 is involved in part in the maintenance of high blood pressure in malignant hypertension, as exemplified by SHRSP.

Amino Acid Sequence↗

Insect resistant rice generated by introduction of a modified delta-endotoxin gene of Bacillus thuringiensis.

As a first step towards development of insect resistant rice we have introduced a truncated delta-endotoxin gene, cryIA(b) of Bacillus thuringiensis (B.t.) which has specific biological activity against lepidopteran insects into a japonica rice. To highly express the cryIA(b) gene in rice the coding sequence was extensively modified based on the codon usage of rice genes. Transgenic plants efficiently expressed the modified cryIA(b) gene at both mRNA and protein levels. Bioassays using R2 generation plants with two major rice insect pests, striped stemborer (Chilo suppressalis) and leaffolder (Cnaphalocrosis medinalis), indicated that transgenic rice plants expressing the CryIA(b) protein are more resistant to these pests than untransformed control plants. Our results suggest that the B.t. endotoxin genes will be useful for the rational development of new rice varieties resistant to major insect pests.

Amino Acid Sequence↗