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Biomedical subjects

J Kubota

Publications and source records attributed to J Kubota.

At least 37 records · Page 2Linked to original sources

Effects of renal denervation on pressure-natriuresis in spontaneously hypertensive rats.

To investigate the role of renal sympathetic nerve activity (RSNA) under developing and established hypertension, renal function was studied in chronically renal-denervated and sham-operated male spontaneously hypertensive rats (SHR) and control Wistar Kyoto rats (WKY) at 8 (early hypertensive) and 22 (established hypertensive) weeks of age. To further characterize the renal pressure-natriuresis-diuresis relationship in SHR, renal perfusion pressure (RPP) was reduced by aortic constriction to the level seen in age-matched WKY and the same studies were repeated. After denervation, urinary sodium excretion (UNaV), fractional excretion of sodium (FENa) and urine flow (UF) were increased in 8-week-old SHR (p < 0.01). With the exceptions of UNaV and FENa in denervated 8-week-old SHR, renal cortical blood flow, glomerular filtration rate, UF, UNaV and FENa decreased with the reduction of RPP in all of the SHR groups. These results suggest that RSNA significantly influences renal sodium and fluid handling, thus contributing to the shifting of the arterial pressure-renal sodium excretion curve to the right along the pressure axis and/or to an increase in the steepness of the relationship in 8-week-old SHR. There appeared to be a marked difference in renal sodium handling between 8- and 22-week-old SHR.

Animals↗

Hemodynamic and neurohumoral responses to exercise in patients with congestive heart failure.

Hemodynamic and neurohumoral responses to supine bicycle exercise were evaluated in 16 patients with congestive heart failure (New York Heart Association functional class II-III) and in 8 normal controls. We determined cardiac output by the dye-dilution method, and forearm hemodynamics by plethysmography. The patients had lower resting cardiac and stroke indexes (p < 0.05) than the normal controls. During exercise, the increase in the cardiac index due to an increase in heart rate, was less than that in the controls. Resting and exercise systemic vascular resistance indices were higher in the patients (p < 0.05). The patients had lower resting forearm blood flow and higher forearm vascular resistance (p < 0.05), and the increases during exercise were comparable in the 2 groups. However, forearm venous tone and venous pressure increased more in the patients (p < 0.05). Exercise duration was shorter in the patients (p < 0.01). Resting plasma angiotensin II and norepinephrine were similar in the 2 groups, but plasma 6-keto-prostaglandin F1 alpha and atrial natriuretic peptide were higher in the patients. During exercise, all of these neurohumoral parameters rose more in the patients than in the controls (p < 0.05). Thus, the patients exhibited impaired central and peripheral hemodynamics both at rest and during exercise. The excessive exercise responses of all of the neurohumoral factors suggest that both vasoconstrictor and vasodilator systems are activated in heart failure.

6-Ketoprostaglandin F1 alpha↗

Long-term alpha 1 blockade does not reverse cardiac hypertrophy in spontaneously hypertensive rats.

Not all antihypertensive drugs induce regression of left ventricular (LV) hypertrophy in hypertension, although they may equally lower blood pressure. The effects of alpha 1-blockers on regression have been inconsistent. In this study, bunazosin, a selective alpha 1-blocker, (15 mg/kg/day in food) was given to male spontaneously hypertensive rats (SHR) from 15 to 35 weeks of age to evaluate its effects on cardiac hypertrophy, hemodynamics, and neurohumoral factors. Age- and sex-matched SHR served as controls. LV function and cardiac output were determined by a micromanometer and thermodilution, respectively. Bunazosin significantly decreased blood pressure in conscious rats (from 209 to 192 mmHg, p < 0.01) but did not reduce LV mass. Heart rate, LV end-diastolic pressure, dp/dtmax, and cardiac output were similar in the 2 groups. Plasma renin activity was unaltered but plasma norepinephrine levels were higher in the treated rats (p < 0.05). Thus, bunazosin produced a significant relative reduction of blood pressure but did not reverse LV hypertrophy in SHR. Inadequate afterload reduction (8%) due to severe hypertension (> 200 mmHg) may explain the absence of regression. The rise of plasma norepinephrine levels may also offset the beneficial effects of bunazosin.

Adrenergic alpha-Antagonists↗

[A study of trientine therapy in Wilson's disease with neurological symptoms].

D-penicillamine, an orally-administered chelating agent, is effective for Wilson's disease (WD). However 25% of WD patients showed serious adverse reactions to D-penicillamine cause this drug to be discontinued after months or years of treatment. For these cases, trientine-2HCl and trientine-4HCl, less toxic agents, are investigated. Three patients with WD, associated with neurological symptoms, were given either trientine-2HCl or trientine-4HCl. These patients had been on therapy with D-penicillamine. Severe adverse reactions had developed during the course of therapy, and D-penicillamine was discontinued, pancytopenia in case 1, nephrotic syndrome in case 2, and myasthenia gravis in case 3. Trientine-2HCl for case 1, and trientine-4HCl for cases 2 and 3 were instituted and continued. The neurological findings in all patients were extremely improved without side effects by trientine therapy. Though the chelating action on copper is weaker than that of D-penicillamine, it is efficient in improvement of the clinical neurological symptoms.

Adolescent↗

Effects of lisinopril upon cardiac hypertrophy, central and peripheral hemodynamics and neurohumoral factors in spontaneously hypertensive rats.

OBJECTIVE: Left ventricular function (LVF) after reversal of left ventricular hypertrophy (LVH) with antihypertensive therapy is still controversial. The present study was undertaken in spontaneously hypertensive rats (SHR) to determine whether LVF of the regressed heart with lisinopril is normally maintained. DESIGN: We compared cardiac function of SHR after reversal of LVH induced by lisinopril with that observed in control SHR and also with effects after a 4-week washout period. METHODS: Administration of lisinopril began at 15 weeks of age and continued for 20 weeks. Cardiac index, renal blood flow, leg muscle blood flow, plasma renin activity, atrial natriuretic peptide level, and norepinephrine concentration were determined. RESULTS: Lisinopril decreased body weight, blood pressure and left ventricular weight and increased leg muscle blood flow; cardiac index and renal blood flow were unaltered. Although norepinephrine concentration was unchanged, plasma renin activity increased and atrial natriuretic peptide decreased in treated SHR. Peak left ventricular pumping ability during volume loading was comparable in the two groups. After a 4-week washout period, left ventricular mass and blood pressure increased but remained lower than controls; cardiac index at rest and during volume loading was similar in the two groups. CONCLUSIONS: These data indicate that LVF of the regressed heart induced by lisinopril was well preserved at rest, during volume loading and also after spontaneous recurrence of hypertension in SHR.

Animals↗

Transesophageal echocardiography with a single-plane probe. Long-axis views of the heart from the apical (transgastric) approach.

The literature suggests that during transesophageal echocardiography (TEE), a short-axis view can be obtained in the gastric position using a single-plane probe. Recently, we have found that a long-axis apical display of the heart can be achieved by placing the tip of the probe in the fundus of the stomach. In a 3-month period, we attempted to obtain this view in 54 consecutive patients. Twelve of the patients had TEE done under general anesthesia, while the other 42 patients had the procedure performed under sedation with midazolam at hospital bedside or as an outpatient. The long-axis transgastric view was obtained in 51 of the 54 patients (94%). The image quality was graded subjectively as good in 39 (72%) and fair in the other 12 patients (22%). This view helped to establish the diagnosis in eight patients (15%) and to increase the level of confidence about the accuracy of the diagnosis in 23 (43%) other patients. Four patients' findings are described. We conclude that the new long-axis transgastric view is easy to obtain, does not add much time to the usual TEE study, does not add to the low complication rate of TEE, and may help to interrogate the distal structures of the heart.

Adolescent↗

Nifedipine in divided doses does not reverse left ventricular hypertrophy in spontaneously hypertensive rats.

This study investigated whether nifedipine administered in divided daily doses would diminish left ventricular hypertrophy (LVH) in spontaneously hypertensive rats (SHR). We administered nifedipine (12 mg/kg/day) in 3 divided doses by gastric gavage to 15-week-old male SHR (n = 10) for 4 weeks. Age- and sex-matched SHR served as controls (n = 10). Left ventricular (LV) function was evaluated by LV catheterization and cardiac output was determined by the thermodilution method. Plasma renin activity (PRA) and plasma norepinephrine levels were measured. Nifedipine significantly decreased blood pressure (p less than 0.01), shortened time constant T (p less than 0.05), and increased cardiac output (p less than 0.05). Nifedipine did not impair the LV systolic and diastolic indices during acute afterload elevation with angiotensin II. LV weight was similar in the 2 groups of rats. While PRA was unaltered, plasma norepinephrine levels were higher in the nifedipine-treated rats (p less than 0.05). These data indicate that nifedipine in 3 divided doses reduced blood pressure in SHR without compromising cardiac function but did not reverse LVH. The short hypotensive duration of nifedipine and its enhancement of sympathetic nervous activity may be responsible for the failure to reverse LVH, despite adequate blood pressure control.

Adrenergic Fibers↗

Kinetic analyses of creatine kinase release patterns in patients with acute myocardial infarction undergoing emergency coronary arteriography.

To quantify the effects of early reperfusion on the size of infarcts, an enzyme indicator was developed: myocardial creatine kinase (CK) release rate (kr), based on a compartmental kinetics model. In 59 patients with acute myocardial infarction (MI) who received intracoronary thrombolysis therapy in the acute phase, the kr showed a good correlation with the flow condition of infarct-related coronary artery and the time required to reach peak enzyme activity. Apparent serum CK disappearance rate (kd') was estimated by using the method of Norris. The kd' was significantly underestimated in patients without reperfusion, suggesting the presence of prolonged enzyme release from the infarcted area. In 22 of 59 patients, who had a first acute anterior MI (left anterior descending arterial lesion), the correction of cumulative enzyme release by myocardial enzyme release (kr) resulted in a closer correlation with chronic phase left ventricular function. Thus, kinetic analyses of serum enzyme release provide a useful means to estimate the infarct size during intracoronary thrombolysis therapy.

Adult↗

Peripheral hemodynamic effects of captopril in patients with congestive heart failure.

In 14 patients with severe congestive heart failure, the effects of captopril on the forearm circulation were evaluated with strain gauge plethysmography. Changes in plasma renin activity, angiotensin II, norepinephrine, epinephrine, bradykinin, prostaglandin E2, and 6-keto-prostaglandin F1 alpha concentrations were also measured. To determine whether the prostaglandins contribute to the peripheral hemodynamic response to captopril, the hemodynamic and hormonal measurements were repeated after pretreatment with indomethacin, an inhibitor of prostaglandin synthesis. Ninety minutes after administering a single dose of captopril (25 mg), mean blood pressure and venous pressure decreased (p less than 0.01 and p less than 0.05, respectively), forearm blood flow and maximum venous volume increased (p less than 0.05 for both), and forearm vascular resistance and forearm venous tone decreased (p less than 0.05 for both). Captopril also improved forearm venous distensibility (p less than 0.05). Pretreatment with oral indomethacin (50 mg) significantly blunted all of these captopril-induced hemodynamic changes. The blockage of the renin-angiotensin system by captopril was unaltered by indomethacin pretreatment. Captopril significantly increased plasma bradykinin, prostaglandin E2, and 6-keto-prostaglandin F1 alpha (p less than 0.05 for each). Indomethacin pretreatment did not affect the captopril-induced increase in bradykinin, but it did completely eliminate the increase in the prostaglandins. Plasma catecholamines did not change with captopril. These data suggest that the vasodilator prostaglandins play a significant role in captopril's peripheral vasodilative effects in congestive heart failure.

6-Ketoprostaglandin F1 alpha↗

Cardiorenal effects of an orally active dopamine prodrug (TA-870) in patients with congestive heart failure.

The effects of TA-870, a newly synthesized orally active dopamine prodrug, on the cardiorenal functions were investigated in 12 patients with severe chronic congestive heart failure. A single oral dose of TA-870 (1,200 mg) improved left ventricular fractional shortening and mean circumferential velocity on M-mode echocardiography (p less than 0.01 for both). Renal plasma flow and glomerular filtration rate improved with TA-870 (p less than 0.01 and p less than 0.05, respectively); urine volume and sodium excretion increased (p less than 0.01 for both). Blood pressure and heart rate did not change during the 4-h experimental period. Mean plasma free dopamine levels peaked 1 h after dosing. These data suggest that the cardiorenal effects of oral TA-870 are comparable with those of continuous intravenous injections of dopamine. Thus, TA-870 appears to be a useful alternative drug to intravenous dopamine.

Adult↗

Long-term prognosis for patients with variant angina and influential factors.

Two hundred forty-five patients with variant angina were followed for an average of 80.5 months (range, 36-184 months). Survival rate at 1, 3, 5, and 10 years was 98%, 97%, 97%, and 93%, respectively. Survival rate without myocardial infarction at 1, 3, 5, and 10 years was 86%, 85%, 83%, and 81%, respectively. By univarite analysis, ST segment elevation in both the anterior and inferior electrocardiographic leads was the most important factor influencing survival, followed by use of calcium antagonists, left ventricular function, smoking, and alcohol intake. The variables that significantly correlated with survival without myocardial infarction were use of calcium antagonists, left ventricular function, extent and severity of coronary artery disease, coronary artery bypass surgery, and disease activity. Multivariate analysis using the Cox proportional hazards model showed that intake of calcium antagonists, extent and severity of coronary artery disease, and ST segment elevation in both the anterior and inferior leads were significant independent predictors of survival without myocardial infarction. We conclude that long-term prognosis for patients with variant angina is relatively good and that use of calcium antagonists improves it.

Adult↗

Isolation of two forms of growth hormone secreted from eel pituitaries in vitro.

Two forms of growth hormone (GH) were purified by chromatofocusing of medium from cultured Japanese eel (Anguilla japonica) pituitaries. The pituitaries were organ-cultured in Eagle's minimum essential medium with Earle's salts. Following polyacrylamide gel electrophoresis of the medium at pH 9.5, two prominent bands were seen with Rf 0.36 and 0.29; they were designated as eGHI and eGHII, respectively. Seven-hundred fifty milliliters of medium, in which 260 pituitaries were cultured for 6-10 weeks, was concentrated by DIAFLO membrane (YM-5) and subjected to gel filtration on a Sephadex G-75 column and to chromatofocusing on a PBE-94 column. eGHI and II were finally purified by gel filtration on a Sephadex G-75 column, yielding 2.0 mg of eGHI and 1.3 mg of eGHII. Both eGHI and eGHII were equipotent to ovine GH in promoting growth of juvenile rainbow trout. The putative GH-producing cells in the proximal pars distalis of the eel pituitary were stained specifically with antisera raised against eGHI or eGHII; no cross-reactivity was seen in the follicular prolactin cells in the rostral pars distalis. As determined by gel isoelectric focusing, eGHI and eGHII have isoelectric points of 6.3 and 6.7, respectively. Identical molecular masses of 23,000 Da were determined by sodium dodecyl sulfate gel electrophoresis. Their amino acid compositions strongly resembled each other; comparison of the partial N-terminal amino acids indicates that sequence 1 to 36 of GHII is exactly the same as 4 to 39 of GHI.

Animals↗

Effects of captopril on peripheral hemodynamics in severe congestive heart failure.

The effects of captopril on the forearm hemodynamics in patients with severe congestive heart failure were studied, using strain-gauge plethysmography. To determine whether prostaglandins are involved in the captopril actions, indomethacin, an inhibitor of prostaglandin synthesis, was administered. In 8 patients, captopril (25 mg) decreased mean blood pressure (P less than 0.01) and venous pressure (P less than 0.05); forearm blood flow (P less than 0.05) and maximum venous volume (P less than 0.05) were increased; forearm vascular resistance (P less than 0.05) and forearm venous tone (P less than 0.05) were decreased. Venous distensibility was improved with captopril (P less than 0.05). All the hemodynamic changes were attenuated by indomethacin (50 mg). Captopril increased circulating bradykinin (P less than 0.05), prostaglandin E2 (P less than 0.05) and 6-keto-prostaglandin F1 alpha (P less than 0.05). Indomethacin did not affect bradykinin level but blocked the increase in prostaglandins. These data suggest that captopril dilates both arterial and venous vessels not only by blocking the renin-angiotensin system but by increasing local or circulating vasodilator prostaglandins.

Blood Pressure↗

Isolation and characterization of chum salmon growth hormone.

Two molecular forms of salmon growth hormone (sGH), sGH I and II, have been isolated from the pituitary glands of the chum salmon (Oncorhynchus keta); a two-step extraction procedure, under alkaline (pH 10) conditions, subsequent to acid-acetone extraction was employed for extraction of the sGHs. They were then purified by iso-electric precipitation at pH 5.6, gel filtration on Sephadex G-100, and high-performance liquid chromatography on ODS. Intraperitoneal injection of sGH I and a combination of sGH I and II at doses of 0.01 microgram/g body wt at different intervals resulted in a significant increase in body weight and length of juvenile rainbow trout. The GH producing cells in the pituitary of mature chum salmon were identified in the proximal pars distalis immunocytochemically with a specific antiserum; no cross-reactivity was seen in the prolactin cells in the rostral pars distalis. A molecular weight of 22,000 was estimated for both sGHs by gel electrophoresis in sodium dodecyl sulfate. Isoelectric points, by gel electrofocusing, of 5.6 and 6.0 were estimated for sGH I and II, respectively, with differences present in the amino acid composition and the N-terminal residue, suggesting that they may be genetic variants coded on two separate genes. The partial amino acid sequences of sGH I at both terminal regions have been determined.

Amino Acid Sequence↗

A new approach for the enzymatic estimation of infarct size: serum peak creatine kinase and time to peak creatine kinase activity.

The relations of several creatine kinase (CK) variables to angiographic left ventricular ejection fraction and abnormally contracting segments in the chronic phase were examined in 2 groups of patients with a first anterior acute myocardial infarction. In group A (n = 22), emergency coronary angiography was performed and nonsurgical early reperfusion was attempted. Such an early revascularization, which was considered partially present in group B (n = 16), which received conventional therapy, shifted the CK time-activity curve to the left and altered its relation to angiographic cardiac function. At similar levels of peak CK, myocardial damage was significantly smaller in patients with successful thrombolysis than in those with unsuccessful reperfusion and conventional therapy (p less than 0.01). In patients whose infarct was considered to be moderate according to peak CK (1,000 to 3,000 U/liter), there was significant correlation between time to peak CK and left ventricular ejection fraction or percent abnormally contracting segments irrespective of their group. The results suggest that one should take into account rapid washout and shorter time to peak CK when estimating enzymatic infarct size in humans. The multivariate analysis of cardiac function with peak CK and time to peak CK resulted in a closer correlation in all patients. Such a correction in the time to peak CK may be a clinically useful approach for better interpretation of infarct size.

Aged↗

Pathogenesis of angina pectoris in patients with one-vessel disease: possible role of dynamic coronary obstruction.

We examined the pathogenesis of angina pectoris in 101 patients with one-vessel disease except those with 99% to 100% occlusion. The attacks could not be induced or could not be reproducibly induced by maximal treadmill exercise at the same hour of different days within a week period in 54 (53.5%) of the patients. In the 47 patients whose attacks were reproducibly induced by the exercise, propranolol, 80 mg orally, did not suppress the attacks in 41 (87.2%) of the patients. Diltiazem, 90 mg, and nifedipine, 20 mg given orally, suppressed the attacks completely in 39 (83.0%) of the 47 patients and in 36 (81.8%) of the 44 patients, respectively. Coronary arteriography showed that dynamic obstruction of the artery supplying the area of myocardium represented by ST segment deviation appeared during the attacks and disappeared with subsidence of the attacks in all 55 patients in whom coronary arteriography was done during the attack. We conclude that angina pectoris is usually caused not by increased myocardial oxygen demand but by dynamic coronary obstruction or by a combination of both in most patients with one-vessel disease.

Adult↗

Development and validation of a salmon growth hormone radioimmunoassay.

A highly specific and sensitive radioimmunoassay (RIA) for the measurement of plasma and pituitary growth hormone (GH) levels in salmonid fishes was developed using an anti-serum raised in rabbit against chum salmon (Oncorhynchus keta) GH (sGH). Pituitary extracts and plasma from chum, coho, masu, and amago salmon, and from rainbow trout and Japanese charr, all exhibited displacement curves parallel to the sGH standard. Samples from the eel, carp, goldfish, and tilapia, as well as plasma from hypophysectomized chum salmon and rainbow trout, all showed negligible cross-reactivity. None of the mammalian or teleostean GH or prolactin preparations tested cross-reacted with the antibody in the assay system. RIA sensitivity was 0.6 ng sGH/ml of plasma when 100 microliter of plasma was employed. Intra- and interassay coefficients of variation were 3.9 and 4.1%, respectively. Plasma GH levels of the mature chum salmon caught in Otsuchi Bay were highly variable, especially in females (20.2 +/- 8.2 ng/ml) as compared with males (16.0 +/- 1.1 ng/ml), and there was no significant change after transfer to fresh water. Whereas there was no change in plasma GH levels in males kept in seawater, the levels in females increased with time in close correlation with the increase in plasma chloride.

Animals↗