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Biomedical subjects

S Satoh

Publications and source records attributed to S Satoh.

At least 559 records · Page 31Linked to original sources

Preparative high-yield electroelution of proteins after separation by sodium dodecyl sulphate-polyacrylamide gel electrophoresis and its application to analysis of amino acid sequences and to raise antibodies.

A method for the preparative high-yield electroelution of proteins from sodium dodecyl sulphate (SDS) polyacrylamide gel strips was established. The method consisted of SDS-polyacrylamide gel electrophoresis, detection of proteins with sodium acetate and electrophoretic elution at 200 V for 3 h by utilizing a horizontal flat-bed gel electrophoresis apparatus. Standard proteins with molecular masses of 14-66 kilodalton (cytochrome c, aldolase, ovalbumin and bovine serum albumin) were recovered with an average yield of 73.6 +/- 2.3%. A membrane-bound protein, rat skeletal muscle Ca(2+)-ATPase (100 kilodalton) was also well recovered (over 60%). This method was applicable to the purification of proteins required for N-terminal amino acid sequencing and to raise antibodies.

Amino Acid Sequence↗

Effects of endothelin on adrenergic neurotransmission in the dog kidney.

Endothelin infused into the renal artery (0.3-3 ng/kg per min) of anesthetized dogs suppressed the increases in renal venous plasma norepinephrine (NE) concentration and calculated NE efflux induced by renal nerve stimulation at low frequencies (0.7-1.2 Hz) but not at high frequencies (2-3.5 Hz). Endothelin failed to affect the decrease in renal blood flow induced by renal nerve stimulation or exogenous NE. These findings suggest that endothelin inhibits NE release during a slight rise in renal nerve activity, while it does not affect alpha-adrenoceptor-mediated vasoconstriction in the dog kidney.

Animals↗

Effects of atrial natriuretic peptide on adrenergically induced norepinephrine release and vasoconstriction in the dog kidney.

The effects of atrial natriuretic peptide (ANP) on the neural control of renal blood flow were examined in anesthetized dogs. Intrarenal arterial infusion of ANP (alpha-hANP, 10 and 50 ng/kg per min) suppressed the decrease in renal blood flow but not the increase in renal venous plasma norepinephrine concentration induced by renal nerve stimulation (1 and 2 Hz, for 1 min). ANP also attenuated the blood flow response to intrarenal arterial injection of methoxamine (5-20 micrograms). These results suggest that ANP acts at a postsynaptic site to suppress adrenergically induced vasoconstriction in the dog kidney.

Animals↗

Serotonin-induced renin release in the dog kidney.

The effect of serotonin (5-HT) on renin release was examined in denervated kidney of the pentobarbital-anesthetized dog. The intrarenal arterial infusion of a large dose of 5-HT (1 micrograms/kg per min) increased the renin secretion rate with an initial decrease and a subsequent increase in renal blood flow. Systemic blood pressure or heart rate was unaffected. The renin release induced by 5-HT was suppressed during intrarenal arterial infusion of a 5-HT1 and 5-HT2 antagonist, methysergide (30 micrograms/kg per min), or a selective 5-HT2 antagonist, ketanserin (3 micrograms/kg per min). A cyclooxygenase inhibitor, indomethacin (5 mg/kg i.v.), also suppressed the 5-HT-induced renin release. These results suggest that stimulation of renal 5-HT receptors, probably of the 5-HT2 type, can induce renin release from the dog kidney, which may be dependent on renal prostaglandin production. The present results, however, do not allow us to conclude that the renal 5-HT receptors play a physiological role in the control of renin release.

Anesthesia↗

Enhancement of propranolol hydrochloride and diazepam skin absorption in vitro: effect of enhancer lipophilicity.

The enhancement of model hydrophilic (propranolol hydrochloride) and lipophilic (diazepam) drug penetration across rat and hairless mouse skin in vitro has been studied. Preliminary experiments established that most n-alkanes having chain lengths of between 7 and 16 promote the flux of both drugs. For propranolol, enhancement varied parabolically with carbon number; for diazepam, heptane was ineffective and all others were essentially equipotent. Enhancement by n-nonane was then compared with that by n-nonanol. Propranolol flux was increased by both enhancers, whereas diazepam penetration was not affected by the less lipophilic alcohol. The enhancement of propranolol by n-nonane and n-nonanol was examined as a function of adjuvant concentration in the applied formulation. Maximum increases in maximum penetration rates of 6.5-fold (n-nonane) and 8.2-fold (n-nonanol) were determined. As expected, the enhancement was saturable, indicative of a maximally perturbed stratum corneum. Finally, the penetration enhancing abilities of six monoterpenes were assessed. The purely hydrocarbon analogues promoted both propranolol and diazepam transport to an extent similar to that of n-nonane. The terpenes with hydrogen-bonding ability, however, only enhanced propranolol flux (at a level comparable to n-nonanol). While the data reported do not directly reveal mechanistic information on percutaneous penetration enhancement, they do provide a starting point for the rational investigation of interrelationships between drug, enhancer, and skin. Such information is clearly essential for the optimization and exploitation of transdermal drug delivery.

Alkanes↗

Pharmacokinetics of SUN 1165, a new antiarrhythmic agent, in renal dysfunction.

The pharmacokinetics of a new Class I antiarrhythmic agent, SUN 1165, has been studied in 32 patients with varying degrees of renal impairment following a single oral dose of 50 mg. The apparent volume of distribution at steady state was 1.48 l.kg-1, the absorption rate constant was 2.2 h-1, and plasma protein binding was 26.8% in subjects with normal renal function. These variables were not altered with renal impairment. More than 60% of SUN 1165 given orally was excreted unchanged via the kidney, both by tubular secretion and glomerular filtration. The elimination rate constant, the apparent total body clearance and the apparent renal clearance were linearly correlated with the endogenous creatinine clearance. The half-time of elimination was 3.4 h in normal subjects and it was prolonged to 23.7 h in severe renal failure (creatinine clearance below 20 ml.min-1.1.48 m-2). Dosage adjustment of SUN 1165 is necessary in renal failure.

Acute Kidney Injury↗

The effects of HA1077 on the cerebral circulation after subarachnoid haemorrhage in dogs.

We examined the effects of the recently developed calcium antagonist HA1077 on cerebral haemodynamics during the chronic stage of the two-haemorrhage canine model system of vasospasm. Regional cerebral blood flow (rCBF), regional cerebral blood velocity and regional cerebral blood volume in the canine parietal cortex were measured by Laser-doppler flowmeter. On the 7th day after the initial injection of autogenous blood, subarachnoid haemorrhage (SAH) produced a significant decrease in rCBF (59% of control, p less than 0.05) and blood velocity (48% of control, p less than 0.05) with no remarkable change in blood volume (108% of control). Bolus intravenous administration of HA1077 (0.1-0.3 mg/kg) dose-dependently increased the rCBF and blood velocity, without significantly changing the blood volume on Day 7 after SAH. HA1077 improves haemodynamic function manifested by an increase in rCBF and velocity in this SAH model, and may be suitable for the treatment of vasospasm in patients with SAH.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Serum erythropoietic inhibitors in patients with pure red cell aplasia.

Inhibitory mechanisms of erythropoiesis in 20 patients with pure red cell aplasia (PRCA) were investigated using the technique of in vitro hematopoiesis and an assay for human parvovirus. Complement-dependent serum inhibitors against late erythroid progenitors (CFU-E) were demonstrated in seven of 19 patients examined, and complement-dependent inhibitors against early erythroid progenitors (BFU-E) were demonstrated in three of these seven patients. Nonspecific and complement-independent inhibitors against CFU-E were thought to be associated with the etiology of PRCA in one patient. Human parvovirus-mediated erythropoietic suppression was demonstrated in a patient with complete remission of acute lymphoblastic leukemia complicated with marrow erythroid aplasia, whose serum showed a perfect inhibition against erythroid progenitor cells. T-cell-mediated erythroid suppression was not demonstrated in the patients examined. These findings reveal that erythroid aplasia is associated with complement-dependent serum erythropoietic inhibitor in some patients (36.8% in the present study) with PRCA, but it is difficult to identify the mechanism of erythroid aplasia in more than half of the patients with PRCA. In addition, our present study discovered the presence of parvovirus-mediated marrow pure red cell aplasia in one adult patient with acute lymphoblastic leukemia.

Adult↗

Tumourous deposition of calcium pyrophosphate dihydrate crystals in the wrist. A case report.

A 63-year-old man had a tumourous deposition of calcium pyrophosphate dihydrate crystals in the palmar aspect of the wrist. Traumatic micro-fracture or osteoarthritis was thought to have triggered the deposition of these crystals. It should be possible to differentiate the lesion clinically and radiologically from tumoural calcinosis, in which the deposits consist of calcium carbonate and/or calcium phosphate.

Calcium Pyrophosphate↗

The role of platelets in the development of cerebral vasospasm.

A possible role of platelet-derived 5-HT was examined concerning the pathogenesis of cerebral vasospasm. Intracisternal injection of 5 ml of platelet-rich plasma (PRP; approximately 7.5 x 10(8) platelets) induced not only acute (1 h) but also chronic (7 days) angiographically evident cerebral vasospasm in dogs. Sympathetic perivascular nerves on cerebral arteries showed no remarkable change following repeated injections of PRP, as the dense distribution of catecholamine-fluorescence and neuropeptide Y-like immunoreactive nerve fibers on Day 7 was comparable to findings in the preinjection controls. While there were no 5-HT-immunoreactive fibers in the cerebral arteries of control animals, numerous 5-HT-immunoreactive fibers were present in the PRP-injected animals. These results suggest that 5-HT, presumably released from extravasated platelets, may be taken up by nerve endings and act as a vasoconstrictor transmitter in the pathogenesis of chronic vasospasm.

Acute Disease↗

Expression of cDNA for batroxobin, a thrombin-like snake venom enzyme.

The cloned cDNA for batroxobin has been expressed in E. coli. Batroxobin could only be obtained as intracellular aggregates of fusion proteins, fused with a small peptide. To obtain the mature batroxobin, the recognition sequence for thrombin was inserted between the peptide and the mature batroxobin. This fusion protein accumulated in an insoluble form and could easily be purified. After site-specific cleavage of the fusion protein with thrombin, recombinant batroxobin was isolated by preparative electrophoresis. Batroxobin with enzymatic activity was obtained by the refolding of recombinant batroxobin.

Amino Acid Sequence↗

Purification and immunohistochemical detection of an embryogenic cell protein in carrot.

An embryogenic cell protein from carrot (Daucus carota L.), designated ECP31 for embryogenic cell protein and with a relative mass of 31,000, was purified by sequential column chromatographies. Its apparent relative mass was estimated to be 120,000 by gel filtration. Immunoblotting and immunohistochemical studies showed that ECP31 was preferentially localized in the peripheral cells of clusters of embryogenic cells in the presence of 2,4-dichlorophenoxyacetic acid (2,4-D) and disappeared during the course of somatic embryogenesis in the absence of 2,4-D. ECP31 began to accumulate on the 33rd day after initiation of cultures of hypocotyl segments on Murashige-Skoog medium with 2,4-D, when callus began to appear on the segments. In dry seeds, lower amounts of ECP31 were located throughout the entire zygotic embryos but not in endosperm. ECP31 was also detected in provascular tissue of malformed somatic embryos.

Journal Article↗

Natriuretic effect of TMB-8 in anaesthetized dogs.

1. Effects of 8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate hydrochloride (TMB-8), an inhibitor of intracellular calcium release, on renal function were examined in anaesthetized dogs. 2. Intrarenal arterial infusion of TMB-8 (0.03 and 0.1 mg/kg per min) increased urine flow rate, urinary sodium excretion and fractional excretion of sodium without affecting blood pressure, renal blood flow or glomerular filtration rate. 3. The results suggest that TMB-8 inhibits tubular sodium reabsorption to induce natriuresis.

Animals↗

Blockade of intracellular actions of calcium may protect against ischaemic damage to the gerbil brain.

1. The brain cytoprotective effects of a putative calcium-associated protein kinase inhibitor, HA1077, as well as a calcium entry blocker nicardipine were evaluated in models of cerebral ischaemia in Mongolian gerbils. Morphological changes characterizing delayed neuronal death of selectively vulnerable CA1 pyramidal neurones in the hippocampus of the Mongolian gerbil brain occurred 7 days after transient bilateral occlusion of the common carotid arteries. 2. A single injection of HA1077 (1 and 3 mg kg-1, i.p.) 5 min after the occlusion led to a dose-dependent protection of the CA1 neurones. Repeated administrations of HA1077 (1 and 3 mg kg-1, i.p., twice daily for 7 days post-ischaemia) revealed an increase in the number of normal cells, compared to findings with a single administration. 3. In contrast to HA1077, nicardipine (0.3 and 1 mg kg-1, i.p.) did not reduce neuronal degeneration. 4. HA1077 did not interact with the ion channel within which MK-801 binds, as determined by receptor binding. 5. The calcium ionophore, A23187, caused a tonic contraction in canine cerebral arterial strips. HA1077, but not nicardipine, relaxed the A23187-induced contraction, concentration-dependently. 6. These results suggest that blockade of the intracellular actions of calcium may provide protection against ischaemic damage in the brain.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Role of renal nerves on pressure natriuresis in spontaneously hypertensive rats.

An abnormal rightward shift of the pressure-natriuresis curve is a well known feature of the renal function in hypertension. The participation of intrinsic neural factors in the kidney in this phenomenon was investigated in anesthetized young and adult spontaneously hypertensive rats (SHR). At 7-8 wk of age, the renal pressure-diuresis curve and pressure-natriuresis curve were shifted to the left in denervated SHR compared with innervated animals. Fractional excretion of sodium was higher, and plasma renin activity was lower in denervated SHR. Glomerular filtration rate was not affected by renal denervation. In 13- to 15-wk-old SHR, renal denervation did not affect the pressure-diuresis and -natriuresis curves, although other parameters were changed compared with the results at 7-8 wk. In Wistar-Kyoto rats, the pressure-diuresis curve was shifted to the left by renal denervation at both ages. These results suggest that the renal nerves have an important effect on the renal pressure-diuresis and -natriuresis curves. However, renal innervation cannot be thought to cause an abnormal rightward shift of the pressure-diuresis and -natriuresis curves in SHR, especially in the established stage of hypertension.

Animals↗

Cerebral vascular effects of peptide histidine methionine in canine and bovine species.

Peptide histidine methionine (PHM) is a neuropeptide with structural homology to vasoactive intestinal peptide (VIP), itself a putative vasodilatory neurotransmitter. Intra-arterial administration of PHM caused a transient, dose-dependent increase in canine vertebral artery blood flow in vivo. PHM was less potent in this effect than VIP. The interaction of PHM with the vasoconstrictor amines, norepinephrine, histamine, and serotonin, was examined using isolated strips of the bovine middle cerebral artery. PHM shifted the concentration-response curves for vasocontraction by norepinephrine and histamine to the right but did not affect the vasocontraction induced by serotonin. These results suggest that PHM may have a role in the regulation of the cerebral circulation.

Animals↗

Action potential of the intramural ureter in the dog.

In 33 adult mongrel dogs, the function of the intramural ureter was investigated. (A) Bipolar electrodes were placed in both the extravesical ureter and the intramural ureter. Then, an electromyogram (EMG) was recorded from two leads. (B) Cystotomy was performed, needle-type electrodes were inserted into the wall of the ureteral orifice and the extravesical ureter, and the EMG was recorded. (C) A special needle which could record EMG and measure pressure simultaneously was prepared. Then EMG and pressure measurements were recorded from the wall of the intramural ureter. In each experiment, action potentials were recorded from the intramural ureter that were similar to those from the extravesical ureter. The pressure in the wall of the intramural ureter showed variations matching the action potentials. From these results, it was evident that active muscle contraction occurred due to the action potential transmitted from the extravesical ureter even in the intramural ureter.

Action Potentials↗

Tone-dependent waterfall behavior during venous pressure elevation in isolated canine hearts.

We examined the "vascular waterfall" hypothesis, which proposes that coronary flow is unaffected by elevations in outflow pressure until the latter reaches a critical threshold level, in 29 isolated canine hearts. In fibrillating hearts vasodilated with adenosine or carbocromen, coronary flow and the coronary pressure-flow relation were not affected by changes in great cardiac vein pressure (PGCV) below a threshold value of 11 +/- 0.9 (mean +/- SEM) mm Hg. Further elevations of PGCV reduced flow and shifted the pressure-flow relation to the right, increasing its pressure-axis intercept (Pf=0). When vasomotor tone was augmented with vasopressin, threshold PGCV increased to 25 +/- 2.7 mm Hg (p less than 0.001). Once again, the pressure-flow relation was unaffected by changes in PGCV below the threshold value and shifted to the right when this value was exceeded. The amount by which spontaneous values of Pf=0 exceeded threshold values of PGCV was greater when vasomotor tone was augmented than during vasodilation. Pf=0 continued to exceed PGCV when the latter was raised above the threshold level. Both Pf=0 and threshold values of PGCV were less during a long diastole than during ventricular fibrillation. We reached the following conclusions. 1) During changes in PGCV below a threshold value, the coronary circulation exhibits traditional waterfall behavior. 2) The threshold pressure for altering waterfall behavior is affected by vascular tone and mechanical activity. 3) Pf=0 remains above PGCV when the latter is increased above the threshold value needed to alter flow.

Animals↗