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Biomedical subjects

Y Saeki

Publications and source records attributed to Y Saeki.

At least 145 records · Page 8Linked to original sources
PubMed1993

Differential control of sympathetic outflow to kidney, heart, adrenal gland, and liver during systemic hypotension induced by cardiac tamponade in anesthetized dogs.

This study was designed to determine if cardiac tamponade-induced hypotension produces differential control in efferent sympathetic nerve activity to the kidney (RNA), heart (CNA), adrenal gland (AdNA), and liver (HNA) in pentobarbital-anesthetized dogs and to define whether systemic baroreceptors modify this response. We recorded RNA, CNA, AdNA, and HNA simultaneously during a 10 min period of sustained hypotension of 50 mm Hg, which was produced by intrapericardial saline infusion at 20 ml/min. When blood pressure reached 50 mm Hg, sympathetic nerve activity to all four organs increased significantly. Following this, RNA decreased significantly below the control (72 +/- 12%) at the end of experiment, while CNA, AdNA, and HNA remained elevated above control values throughout the experiment. Renal sympathoinhibition was reversed by cervical vagotomy, whereas this had no effect on CNA, AdNA, and HNA responses to hypotension. Additionally, the combined denervation of vagal, carotid sinus, and aortic nerves did not show any significant change in any variables. Thus these results indicate that hypotension due to cardiac tamponade in dogs produces an initial equivocal sympathoexcitation to the kidney, heart, adrenal gland, and liver followed by vagal afferent-mediated sympathoinhibition to the kidney but sustained excitation to the other three organs.

Adrenal Glands↗
PubMed1992

Human peripheral blood lymphocytes express D5 dopamine receptor gene and transcribe the two pseudogenes.

Sequential reverse transcription and polymerase chain reaction (RT-PCR) of the mRNA were used to investigate the expression of dopamine receptors in human peripheral blood lymphocytes. The RT-PCR products contained three types of sequences, each corresponding to those of the D5 dopamine receptor gene and the two related pseudogenes. The lymphocyte cDNA library also contained the clones encoding parts of the three genes. Binding profiles of dopaminergic ligands to the lymphocytes were similar to those for the native neuronal membranes.

Benzazepines↗
PubMed1992

Differential regulation of rat AT1a and AT1b receptor mRNA.

Rat type 1 angiotensin II receptor has two subtypes, namely type 1a and type 1b. The regulation of the expressions of these two subtype receptor mRNAs was studied by using a competitive polymerase chain reaction method. The expression of the type 1a mRNA in the liver was negatively and that of the type 1b mRNA in the adrenal was positively modulated by bilateral nephrectomy. In the ventricle of 16 week old Spontaneously hypertensive rat, the expression level of the AT1b receptor mRNA was higher than that in the ventricle of the age-matched Wistar-Kyoto rat, while the expression levels of the AT1a mRNA in the ventricle were almost similar between the two strains at this age. Although type 1a and type 1b have almost similar functional properties, the expressions of their mRNAs were differentially regulated.

Adrenal Glands↗
PubMed1992

A novel mutant (transthyretin Ile-50) related to amyloid polyneuropathy. Single-strand conformation polymorphism as a new genetic marker.

DNA sequence polymorphisms in transthyretin (TTR) genes were investigated by single-strand conformation polymorphism (SSCP) analysis of polymerase chain reaction products. The amplified DNA fragments that encode each exon of the normal TTR gene showed two bands, representing the two complementary single strands of DNA. In one patient with amyloid polyneuropathy, the exon 3 DNA showed a unique, aberrant migration pattern. Direct sequencing analysis of the amplified exon 3 revealed a single base change (G-to-T), resulting in a novel amino acid substitution (Ser-50----Ile). We also present the SSCP patterns for five known Japanese TTR variants.

Amyloidosis↗
PubMed1992

Transfer of multiple sclerosis into severe combined immunodeficiency mice by mononuclear cells from cerebrospinal fluid of the patients.

To investigate the mode of the pathogenesis of multiple sclerosis (MS), we transferred cerebrospinal fluid (CSF) cells, predominantly mononuclear cells, from MS patients at both exacerbation and remission stages of the disease into severe combined immunodeficiency mice by intracisternal injection. As controls, (i) CSF cells from patients with cervical spondylosis and (ii) peripheral blood mononuclear cells from normal individuals were transferred. Four to 6 weeks after transfer, most mice transferred with CSF cells from MS patients at the exacerbation stage of the disease developed paralysis and ataxia. The histopathological examination on the sacrificed mice revealed multiple scattered, discrete lesions localized in the white matter of the brainstems and spinal cords. These lesions were characterized by various degrees of tissue necrosis, involving inflammatory-cell infiltration. Most infiltrating cells were macrophages, although a smaller number of granulocytes appeared in several foci. Reactive astrocytic gliosis was also seen around the necrotic foci. Furthermore, these lesions exhibited demyelination. These histopathological changes are similar to those seen in MS. In contrast, none of the severe combined immunodeficiency mice transferred with CSF cells from MS patients at the remission stage of the disease, or with CSF cells from the patients with cervical spondylosis, or with peripheral blood mononuclear cells from normal individuals showed any such histopathological changes. These observations provide convincing direct evidence of encephalitogenicity of mononuclear cells in CSF from MS patients at the exacerbation stage of the disease.

Animals↗
PubMed1992

A multicenter comparison of nicorandil and diltiazem on serum lipid, apolipoprotein, and lipoprotein levels in patients with ischemic heart disease.

The effects of nicorandil and diltiazem on serum lipid, apolipoprotein, and lipoprotein levels in 37 patients with ischemic heart disease were examined in a randomized, multicenter study. Nicorandil (n = 20, 10-40 mg/day, b.i.d.) and diltiazem (n = 17, 60-240 mg/day, b.i.d.) were administered for 12 weeks. Both nicorandil and diltiazem administration showed an effective antianginal effect. Diltiazem administration showed a significant hypotensive action. There were no significant changes in serum lipids, apolipoproteins, and lipoproteins for both nicorandil and diltiazem. There were no significant changes in body weight, uric acid, and fasting blood sugar levels during the test period for both drugs. These data show that nicorandil, like diltiazem, does not have any adverse effects on lipid metabolism and that it is a favorable drug to use as an agent for treating arteriosclerotic heart disease.

Aged↗
PubMed1992

Increase in cardiac muscle fructose content in streptozotocin-induced diabetic rats.

To evaluate the activation of the sorbitol pathway in cardiac muscle in diabetic rats, we measured sorbitol, fructose, and myo-inositol content in cardiac tissue obtained from control and streptozotocin-diabetic rats, with or without an 8-week insulin treatment, using gas chromatography-mass spectrometry (GC-MS). Cardiac fructose and sorbitol content in 10-week diabetic rats increased by 60-fold and 3.9-fold of those of control rats, respectively (P less than .001). In contrast, cardiac myo-inositol content in 10-week diabetic rats decreased to 56% (P less than .025) of the control value. The abnormalities in cardiac fructose, sorbitol, and myo-inositol content were completely normalized by the 8-week insulin treatment, which was initiated 2 weeks after the induction of diabetes. There was no difference in cardiac aldose reductase activity between control and diabetic rats. However, cardiac sorbitol dehydrogenase activity in diabetic rats was 151% (P less than .005) higher than that of control rats, although hepatic sorbitol dehydrogenase activity was not different between the two groups. These results indicate that the sorbitol pathway is significantly activated in cardiac tissue obtained from streptozotocin-induced diabetic rats, which results in the marked cardiac accumulation of fructose.

Aldehyde Reductase↗
PubMed1992

Acute effect of hypobaria and hypoxia on renal nerve activity in anaesthetized rabbits.

To determine the acute effect of reduced barometric pressure and hypoxia on renal nerve activity, urethane-anaesthetized and mechanically ventilated rabbits were randomly exposed to the following four separate conditions in a decompression chamber: hypoxic hypobaria (n = 7), hypoxic normobaria (n = 5), normoxic hypobaria (n = 8) and slow normoxic hypobaria (n = 7). A combination of rapid decompression and simultaneous adjustment of inspired PO2 was used to simulate an altitude of 6600 m, and renal nerve activity and haemodynamics, such as systemic blood pressure and heart rate, were measured. During both hypoxic hypobaria and hypoxic normobaria, there were significant and similar increases in renal nerve activity at 6600 m (54 +/- 7% and 61 +/- 13% from each baseline, respectively). However, there were no changes in renal nerve activity during normoxic hypobaria or slow normoxic hypobaria with decompression rates of 1000 or 400 m min-1, respectively. From these results, we conclude that a reduction in barometric pressure without hypoxia does not affect renal nerve activity in anaesthetized rabbits.

Anesthesia↗
PubMed1992

Abnormalities in cardiac alpha 1-adrenoceptor and its signal transduction in streptozocin-induced diabetic rats.

To investigate a mechanism of diabetic cardiomyopathy, we examined an alteration of cardiac alpha 1-adrenoceptor (alpha 1-AR) signaling in streptozotocin-induced diabetic rats. In diabetes, the cell surface alpha 1-AR concentration on isolated cardiac myocytes decreased by 45% without any change in the dissociation constant, and, moreover, norepinephrine (NE)-stimulated ventricular inositol 1,4,5-trisphosphate (IP3) production was also decreased by 34%. In contrast, basal ventricular protein kinase C (PKC) activity was elevated in both cytosolic (by 98%) and membrane (by 41%) fractions in diabetes. All of these abnormalities seen in diabetes were reversed by chronic insulin treatment. Rapid activation of PKC by phorbol ester in the normal rat heart revealed decreases in both receptor number (by 19%) and NE-stimulated IP3 production (by 21%). These results indicate that the impairment of cardiac alpha 1-AR signaling is closely associated with the diabetic state and may be linked, at least in part, with the abnormal activation of cardiac PKC.

Animals↗
PubMed1992

Spatial and temporal differing control of sympathetic activities during hemorrhage.

We performed simultaneous multifiber recordings of cardiac, renal (RNA), hepatic (HNA), adrenal, and splenic sympathetic nerve activities during 10 min of sustained hemorrhagic hypotension to a mean blood pressure of 50 mmHg. One minute after bleeding in dogs with intact baroreceptors, all measured nerve activities increased significantly, and a gradual decline toward prebleeding level followed. Only RNA showed a great inhibition below prebleeding level. In cervically vagotomized dogs, all nerve activities showed significantly higher levels than prebleeding control throughout the experiment. The initial increase in HNA observed at 1 min postbleeding in animals with intact baroreceptors was attenuated. HNA in the vagotomized group showed a gradual increase so that 5 min postbleeding, HNA reached a peak level that was maintained until the end of the experiment. Sympathoinhibition in RNA and decrease in heart rate during hemorrhagic hypotension were reversed to significant increases after vagotomy. In contrast, animals with denervation of the carotid sinus and aortic nerves showed initial increases in nerve activities followed by recovery to prebleeding control level within 2 min postbleeding. After complete denervation of systemic baroreceptors, rapid hemorrhage did not cause any significant change in sympathetic nerve activity in any nerve. These results indicate that early reflex response to hemorrhage in regional sympathetic nerves is unidirectional sympathoexcitation mediated by summative unloading of both arterial baroreceptors and cardiopulmonary receptors. When greater than 1 min passed after bleeding and sustained hypotension of 50 mmHg was established, a reflex mechanism through the vagal afferents participated to inhibit the unidirectional sympathoexcitation mediated by unloading of arterial baroreceptors, with different magnitude in different innervated organs.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands↗
PubMed1992

Pulmonary vascular response to anaphylaxis in isolated canine lungs.

We determined changes in vascular resistance and microvascular permeability during anaphylactic reaction in isolated canine lungs perfused at constant pressure with autologous blood. In lungs with anaphylaxis induced by an intra-arterial injection of Ascaris suum antigen (10 mg), pulmonary vascular resistance and capillary pressure assessed as double occlusion pressure increased transiently by 10 times and 6.3 mmHg, respectively. Pre- to postcapillary vascular resistance ratio decreased from 0.89 +/- 0.05 to 0.21 +/- 0.06, suggesting predominant pulmonary venoconstriction. In lungs perfused in the antidromic direction from the pulmonary vein to the artery, anaphylaxis caused marked precapillary vasoconstriction, consistent with pulmonary venoconstriction. Vascular permeability assessed using the capillary filtration coefficient and isogravimetric capillary pressure did not change significantly for 3 h in either group. No changes were found in any variables in the saline-injected control lungs. The final weight of the anaphylactic lungs was significantly greater than that of the control lungs. Thus we conclude that anaphylaxis in isolated canine lung produces an increase in capillary pressure due to pulmonary venoconstriction without significant changes in vascular permeability. Pulmonary edema accompanied by anaphylactic hypotension may result from an increase in pulmonary hydrostatic intravascular pressure but not an increase in pulmonary vascular permeability.

Anaphylaxis↗
PubMed1992

Effects of lisinopril and low-dose trichlormethiazide on lipoprotein metabolism in patients with mild to moderate hypertension.

Fifty-six hypertensive patients were recruited to participate in a 12 week, randomised, multicentre trial to compare the effects of lisinopril (n = 31) and low-dose trichlormethiazide (n = 25) administration on blood pressure and lipoprotein metabolism. Both systolic and diastolic BPs decreased significantly after administration of lisinopril (5-40mg/day, mean dose 11 mg/day) and trichlormethiazide (2.0-4.0 mg/day, mean dose 2.2 mg/day). There were no significant changes in lipids, lipoproteins or apolipoproteins with either drug for 12 weeks and no significant differences between the two drugs for these parameters. It is concluded that lisinopril and low-dose trichlormethiazide administration are effective antihypertensive measures without any adverse effects after 12 weeks on lipoprotein metabolism in patients with mild to moderate essential hypertension.

Adult↗
PubMed1991

New mutant gene (transthyretin Arg 58) in cases with hereditary polyneuropathy detected by non-isotope method of single-strand conformation polymorphism analysis.

Single-strand conformation polymorphism (SSCP) was analyzed to detect a mutation in the transthyretin (TTR) gene from the mother and son showing polyneuropathy with carpal tunnel syndrome. DNA segments containing TTR coding sequence were amplified by polymerase chain reaction, heat denatured and electrophoresed on a neutral polyacrylamide gel. The single-stranded DNA fragments in the gel were transferred to a nylon membrane and hybridized with biotinylated TTR cDNA probe, followed with chemiluminescent DNA detection. The mobility shift was found in the fragments of exon 3 from the patients' DNA. Sequencing analyses of the exon 3 confirmed a T----G base change, resulting in a Leu 58----Arg substitution. TTR Arg 58 is the first mutant TTR gene that has been detected by SSCP analysis. The rapid and sensitive detection of new mutations at various sites on the TTR gene is hereafter possible by the present method in the facilities for non-radioactive experiments.

Adult↗
PubMed1991

Activation dependence of isotonic transient in response to step tension reduction in cardiac muscle segment during barium contracture.

To clarify the activation-dependence of dynamic mechanical characteristics of contracting cardiac muscle, we analysed the healthy central segment length (SL) response to step decrease in tension at two different levels of barium contracture (0.2 mM and 0.5 mM Ba2+) in rat papillary muscles with a fixed initial SL. The time course of this response is thought to reflect the kinetics of actin-myosin interaction. The muscle was released stepwise from the steady contracture tension (Tc) to new steady tension levels (Tr) of varying magnitudes at 22 degrees C. The SL responses consisted of four phases at Tr/Tc greater than 0.3. The amplitude of shortening in the second phase, after the initial rapid and minute shortening in the first phase, increased with an increase in amplitude of step tension reduction, and was greater at the higher activation level when compared at an identical amount of Tr/Tc. The fourth phase, after the remarkable lengthening in the third phase, was an extremely slow and minute shortening toward a new steady SL under the new tension. The duration of the second and third phase was quite insensitive to activation level at Tr/Tc greater than 0.85, but became longer at the higher activation level with larger amounts of tension reduction. The velocity measured from the initial quasi-steady SL shortening in the second phase increased significantly with the increase in activation level. These results are discussed in terms of cross-bridge kinetics underlying the isotonic SL transients at two different activation levels.

Animals↗
PubMed1991

Hyperthyroid dog left ventricle has the same oxygen consumption versus pressure-volume area (PVA) relation as euthyroid dog.

We studied the effects of hyperthyroidism on the relation between O2 consumption (Vo2) and the pressure-volume area (PVA) of the left ventricle (LV) in dogs. PVA is a measure of the total mechanical energy generated per beat of LV. Dogs were treated by daily intramuscular injection of 0.3 or 1.0 mg/kg L-thyroxine over 2-5 weeks. Hyperthyroid dogs had a 40 times higher serum T4, a 40% higher sinus heart rate, and a 35% higher LV Emax (an index of ventricular contractility) than euthyroid dogs. Hyperthyroid dog hearts had linear Vo2-PVA relations like euthyroid dog hearts. The regression line was Vo2 = A x PVA + B, where A was 2.30 (dimensionless) and B was 0.53 J/beat per 100 g LV. B was significantly increased with dobutamine and decreased with propranolol, whereas A was not significantly changed by them. These A and B values were comparable to euthyroid data. Hyperthyroidism did not significantly affect myosin Ca-ATPase activity and V3-type myosin predominance, but increased the speed of the force transient response to length perturbation by 20%-70%, suggesting similar increases in crossbridge cycling rate. We conclude that in spite of accelerated crossbridge cycling rate the Vo2-PVA relation was not altered by hyperthyroidism in dogs.

Animals↗
PubMed1991

Effects of vasopressin on gastric mucosal blood flow in portal hypertension.

In patients with portal hypertension, bleeding from the gastric mucosa is common, and is often treated with vasopressin (VP). VP reduces the portal pressure by contracting the arterioles of the abdominal organs. In normal rats, VP reduces the gastric mucosal blood flow (GMBF). However, it is not sure whether the reduction of the portal pressure by VP actually reduces the GMBF in patients with portal hypertension. Here, we studied the effects of VP on the GMBF of 24 patients with portal hypertension resulting from cirrhosis. The ICG15 test was done for 20 of the patients. We measured the GMBF of the antrum and body of the stomach using a laser Doppler flowmeter (Peliflux PF 2) connected with a gastrofiberscope without VP on one day and about 10 min after the start of administration of VP (0.4 U/min, i.v.) on another day. Unexpectedly, the GMBF was increased with VP in 14 of 22 patients at the antrum and in 19 of 24 patients at the body of the stomach. In the body of the stomach, there was correlation between the increase in the GMBF caused by VP and the results of the ICG15 test. A high ICG15 reflects high portal pressure, so this finding indicates that in high portal pressure, the GMBF is increased by VP, and in low portal pressure, the GMBF is decreased by VP.

Animals↗
PubMed1991

Cross-bridge movement in fast and slow skeletal muscles of the chick.

1. Fast (posterior latissimus dorsi, PLD) and slow (anterior latissimus dorsi, ALD) muscles of the chick were studied by time-resolved X-ray diffraction using a synchrotron radiation source. 2. In both muscles and at both 20 and 30 degrees C, intensities of the X-ray equatorial reflections changed faster than tension at the beginning of tetanus. When the intensity change was converted into the mass transfer from the thick to the thin filament, the difference between the half-rise times of the transfer and tension development at 20 degrees C was 140 ms in ALD and 37 ms in PLD. At 30 degrees C it was 110 ms and 10-20 ms for ALD and PLD respectively. 3. These results indicate that in the early stage of contraction, some of the myosin heads in the vicinity of the thin filament are developing little or no tension, and suggest that the fast and slow muscles differ in the transition rate of myosin heads from the state of attachment with low tension to that with high tension.

Actins↗