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Biomedical subjects

M Sakuma

Publications and source records attributed to M Sakuma.

At least 127 records · Page 7Linked to original sources
PubMed1992

Effect of slow release nifedipine tablets in patients with essential hypertension.

The antihypertensive effect of slow release nifedipine (CAS 21829-25-4) tablets (20 mg, Adalat) administered once or twice daily was studied in patients with essential hypertension of WHO stage I or II. Ambulatory blood pressure was monitored by a finger volume oscillometric device every 5 min for 24 h before and during the treatment with nifedipine. Whether administered once or twice daily, nifedipine tablets dit not change the pattern of circadian blood pressure variation; i.e. diurnal rise and nocturnal fall. Twice daily administration induced a significant downward shift in the blood pressure pattern. In other words, further hypotensive effect was observed during the night when the blood pressure was already low. On the other hand, administration once daily in the morning lowered daytime blood pressure without affecting blood pressure during the night. The duration of action of nifedipine tablets administered once daily was 12 h or more. In the acute experiment using 20 mg tablets of nifedipine, plasma concentration of nifedipine was well correlated with the percentage change in mean blood pressure. The minimal effective plasma concentration of nifedipine was estimated to be 13.4 ng/ml. However, in chronic treatment, nifedipine lowered blood pressure at the plasma concentration of 10 ng/ml. The results indicate that nifedipine tablets administered once daily provide an effective antihypertensive regimen for controlling daytime hypertension with minimal antihypertensive effect during the night.

Adult↗
PubMed1992

[A case of extra-anatomic bypass for ruptured thoracoabdominal aortic aneurysm with tuberculosis].

Now aneurysmectomy and graft replacement is the most popular surgical method of aortic aneurysm, but there are many opinions about surgical methods and assist circulation for emergency operation of ruptured aortic aneurysm. We experienced the case of ruptured thoracoabdominal aortic aneurysm with tuberculosis, and rescued the patient by extra-anatomic bypass (EAB). A 60-year-old woman, who had been treated with tuberculosis for about 40 years, was operated on for cold abscess of her left psoas muscle by other orthopedic surgeons. At that time, massive bleeding happened, and she was transferred to us under diagnosis of ruptured thoracoabdominal aortic aneurysm. EAB, as emergency operation, was done because we considered it was dirty and dangerous to replace the prosthesis beside the abscess. The postoperative course was almost uneventful except the evidence of Gaffky's first stage. We considered EAB was an useful method for emergency cases and some infectious aortic aneurysms.

Aorta, Abdominal↗
PubMed1991

Assay of fatty acid omega-hydroxylation using high-performance liquid chromatography with fluorescence labeling reagent, 3-bromomethyl-7-methoxy-1,4-benzoxazin-2-one (BrMB).

A sensitive nonradioisotopic method is reported for measuring microsomal lauric acid omega-hydroxylation activity. The assay is based upon separation and detection of 12-hydroxylauric acid formed by means of high-performance liquid chromatography following fluorescence labeling of the carboxyl group with 3-bromomethyl-7-methoxy-1,4-benzoxazin-2-one (BrMB). The use of 10-hydroxycapric acid as an internal standard affords the accurate and reproducible assay. The differential effect of dehydroepiandrosterone, a peroxisome proliferator, on the omega-hydroxylation activity in the liver and kidney of rats is also reported.

Animals↗
PubMed1991

Differential phenotypic expression by three mutant alleles in familial lecithin:cholesterol acyltransferase deficiency.

Familial deficiency of lecithin:cholesterol acyltransferase (LCAT) is an autosomal recessive disorder characterised by abnormalities of all plasma lipoprotein classes and by abnormal deposition of unesterified cholesterol in tissues. To elucidate the molecular basis of the disease, the LCAT genes of three unrelated Japanese patients were amplified by means of the polymerase chain reaction. Direct sequencing of the amplified fragments covering all exons and junctions showed that the patients are homozygotes for separate gene mutations. In one patient a 3 bp insertion, which should cause a substantial change in the enzyme structure, was found in exon 4; he had near absence of LCAT mass and activity. Two separate missense mutations were identified in exon 6 of the other two patients, who produced functionally defective enzymes that differed widely in specific activity. The replacement of asparagine228 with positively charged lysine completely abolished enzyme activity, whereas the other, conservative, aminoacid substitution (methionine293----isoleucine) gave rise to a partially defective enzyme. These results show that distinct mutations cause differences in plasma LCAT activity and LCAT mass, ultimately leading to differential phenotypic expression of familial LCAT deficiency.

Adult↗
PubMed1991

Lecithin-cholesterol acyltransferase (LCAT) deficiency with a missense mutation in exon 6 of the LCAT gene.

The plasma enzyme, human lecithin-cholesterol acyltransferase (LCAT) is responsible for the majority of cholesterol ester formation in human plasma and is a key enzyme of the reverse transport of cholesterol from peripheral tissue to the liver. We sequenced genomic DNA of the LCAT gene from a Japanese male patient who was clinically and biochemically diagnosed as a familial LCAT deficiency. Analysis of all exons and exon-intron boundaries revealed only a single G to A transition within the sixth exon of both allele of the gene, leading to the substitution of methionine for isoleucinle at residue 293 of the mature enzyme. This mutation creates a new hexanucleotide recognition site for the restriction endonuclease Ndel. Familial study of Ndel digestion of the genomic DNA and determination of plasma LCAT activity established that the patient and his sister whose plasma LCAT activity were extremely reduced were homozygous and his children whose plasma LCAT activity were about half of normal controls were heterozygous for this mutation.

Base Sequence↗
PubMed1991

Characteristics of dehydroepiandrosterone as a peroxisome proliferator.

Treatment of rats with dehydroepiandrosterone (300 mg/kg body weight, per os, 14 days) caused a remarkable increase in the number of peroxisomes and peroxisomal beta-oxidation activity in the liver. The activities of carnitine acetyltransferase, microsomal laurate 12-hydroxylation, cytosolic palmitoyl-CoA hydrolase, malic enzyme and some other enzymes were also increased. The increases in these enzyme activities were all greater in male rats than in female rats. Immunoblot analysis revealed remarkable induction of acyl-CoA oxidase and enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase bifunctional enzyme in the liver and to a smaller extent in the kidney, whereas no significant induction of these enzymes was found in the heart. The increase in the hepatic peroxisomal beta-oxidation activity reached a maximal level at day 5 of the treatment of dehydroepiandrosterone and the increased activity rapidly returned to the normal level on discontinuation of the treatment. The increase in the activity was also dose-dependent, which was saturable at a dose of more than 200 mg/kg body weight. All these features in enzyme induction caused by dehydroepiandrosterone correlate well with those observed in the treatment of clofibric acid, a peroxisome proliferator. Co-treatment of dehydroepiandrosterone and clofibric acid showed no synergism in the enhancement of peroxisomal beta-oxidation activity, suggesting the involvement of a common process in the mechanism by which these compounds induce the enzymes. These results indicate that dehydroepiandrosterone is a typical peroxisome proliferator. Since dehydroepiandrosterone is a naturally occurring C19 steroid in mammals, the structure of which is novel compared with those of peroxisome proliferators known so far, this compound could provide particular information in the understanding of the mechanisms underlying the induction of peroxisome proliferation.

Animals↗
PubMed1991

Substance P-evoked release of GABA from isolated spinal cord of the newborn rat.

Isolated spinal cords of newborn rats were perfused with artificial cerebrospinal fluid and the effects of substance P and its analogs on the release of endogenous GABA were examined. Application of substance P evoked a dose-dependent release of GABA from spinal cords. The threshold concentration of substance P for induction of a significant increase in the GABA release was 3 microM. The substance P-evoked GABA release was neither blocked by removal of Ca2+ from perfusion medium nor by tetrodotoxin. In contrast, the GABA release evoked by high K+ (90 mM) was abolished in Ca(2+)-free medium, and the GABA release evoked by veratridine (5 microM) was suppressed by tetrodotoxin (1 microM). A GABA uptake inhibitor, cis-4-hydroxynipecotic acid, markedly augmented the GABA release induced by high K+, but not that induced by substance P or veratridine. These results suggest the possibility that a carrier-mediated mechanism might be involved in the GABA release induced by substance P, as well as by veratridine, in the newborn rat spinal cord. Two N-terminal fragments of substance P, substance P free acid and substance P1-10 amide, as well as [D-Arg1,D-Trp7,9,Leu11]substance P (spantide), evoked an increase in the GABA release, whereas substance P1-6, and a C-terminal fragment, substance P5-11 were inactive. Somatostatin and compound 48/80 also evoked a GABA release, which was independent of external Ca2+ and resistant to tetrodotoxin. [D-Pro4,D-Trp7,9,10]substance P4-11 (10-15 microM) inhibited the GABA release evoked by substance P, somatostatin and compound 48/80.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1991

Substance P-evoked release of acetylcholine from isolated spinal cord of the newborn rat.

Isolated spinal cords of newborn rats were perfused with artificial cerebrospinal fluid and the release of endogenous acetylcholine was measured using high-performance liquid chromatography with an electrochemical detection system. Application of high-K+ (90 mM) medium evoked about an eight-fold increase in the acetylcholine release, and the K(+)-evoked release was Ca2+ dependent. Veratridine (20 microM) also evoked about a four-fold increase in the acetylcholine release, and this increase was suppressed by 0.2 microM tetrodotoxin. Application of substance P at 0.3-3 microM evoked a concentration-dependent release of acetylcholine. The substance P-evoked acetylcholine release was Ca2+ dependent and abolished by tetrodotoxin. Neurokinin A, neurokinin B, acetyl-Arg6-septide and senktide (3 microM each) also evoked a release of acetylcholine. Electrophysiological experiments using isolated spinal cords of newborn rats showed that bath application of substance P induced a depolarization of motoneurons, which was enhanced by edrophonium. This enhancement of substance P-induced depolarization by edrophonium disappeared in a low-Ca2+ medium or in the presence of atropine and dihydro-beta-erythroidine. In the presence of edrophonium and dihydro-beta-erythroidine, substance P induced an inhibition of monosynaptic reflex, and this inhibition was abolished by atropine. These results suggest that substance P and other tachykinins induce a release of acetylcholine from the newborn rat spinal cord by exciting cholinergic neurons.

Acetylcholine↗
PubMed1991

Effect of pericardium on regional myocardial systolic function in acute ischemia.

To know whether or not the pericardium affects regional myocardial systolic function in acute ischemia, we measured ischemic and non-ischemic segment lengths of the left ventricle using ultrasonic crystals in 10 open-chest dogs with the pericardium preserved. When the left ventricular pressure and segment lengths were stable after left circumflex coronary occlusion, we opened the pericardium widely. After coronary occlusion, end-diastolic length (EDL) in ischemic and non-ischemic segments increased, and the ischemic segment showed paradoxical systolic expansion while the non-ischemic segment increased its active shortening. After pericardiectomy, heart rate, left ventricular systolic pressure, and peak positive and negative dP/dt did not change. EDL in ischemic and non-ischemic segments further increased from 12.02 +/- 0.18 to 12.50 +/- 0.16 mm (mean +/- S.E., p less than 0.01) and from 11.12 +/- 0.20 to 11.45 +/- 0.18 mm (p less than 0.05), respectively, despite the concomitant fall in left ventricular end-diastolic pressure (LVEDP) from 12.4 +/- 0.6 to 10.6 +/- 0.8 mmHg (p less than 0.01). End-systolic length in ischemic and non-ischemic segments also increased from 12.37 +/- 0.25 to 12.70 +/- 0.20 mm (p less than 0.05) and from 8.50 +/- 0.13 to 8.74 +/- 0.13 mm (p less than 0.01), respectively, although the left ventricular end-systolic pressure did not change. Maximum expanded systolic length of the ischemic segment also increased from 12.99 +/- 0.20 to 13.42 +/- 0.16 mm (p less than 0.01). These results indicate that, in acute ischemia, the pericardium inhibits paradoxical systolic expansion of the ischemic region and increase in end-systolic length of non-ischemic segment. Thus, it is concluded that the pericardium modifies the regional myocardial systolic function in acute ischemia, perhaps through the mechanical restraint of the pericardium.

Animals↗
PubMed1991

Incidence of retinoblastoma in Nagasaki Prefecture, Japan.

From 1965 to 1986, thirty-four patients with retinoblastoma were born in Nagasaki Prefecture, Japan, 23 with unilateral and 11 with bilateral retinoblastoma. The incidence of retinoblastoma was calculated to be approximately 1 in 16,053 births; it was bilateral in 1 in 49,618 births. There was no significant difference in the incidence of retinoblastoma between urban and rural areas. In Shimabara district it was 1 in 10,331 births--much higher than in any other district of Nagasaki Prefecture. Historically, almost all the natives had been killed in the Shimabara War in 1637, and then people immigrated to Shimabara mainly from Hyogo, Aichi and Shizuoka Prefectures. The authors compared the incidence and distribution of retinoblastoma in these three prefectures with the figures in Shimabara. The incidence in the Tamba and Tajima districts of Hyogo Prefecture was 1 in 10,570 and 1 in 10,411, respectively, very similar to that in Shimabara. The authors wonder if this similarity is only an accidental coincidence when the historical relationship among the three districts is considered.

Eye Neoplasms↗
PubMed1991

[Clinical investigation on the adjunctive method in the surgery of thoracic aortic aneurysms--comparison of the temporary bypass and partial extracorporeal bypass].

Since 1980, two different operative strategies were employed during resection to provide distal aortic perfusion by temporary bypass (Group "TB", 39 patients) or partial extracorporeal bypass (Group "PEC", 39 patients) in the operation for the thoracic descending aortic aneurysms or the dissecting aortic aneurysms with DeBakey type III. No significant differences were found in the patient population or the operative procedures between two groups. Mean bypass flow in Group "PEC" was 1850 +/- 70 (ml/min), which is significantly higher than in Group "TB" (1000 +/- 240 ml/min). However, there were no significant differences in the distal aortic pressure between two groups, which was due to administration of vasodilators. Platelet counts in Group "PEC" were significantly lower in the postoperative courses, probably caused by the use of roller pumps or suckers. The incidence of the postoperative renal dysfunction was almost the same in two groups. Cardiac functions during temporary bypass were suppressed by the aortic cross-clamping, therefore, it is necessary to evaluate the cardiac function preoperatively in employing this method. Partial extracorporeal bypass has the disadvantages of the requirement for full heparinization, but it can be indicated to almost all cases, even to the patients with poor cardiac function. It also has the advantage to maintain the distal perfusion in the unexpected intraoperative situations. The method of distal aortic perfusion should be determined by patient-related and disease-related factors.

Aged↗
PubMed1990

Left ventricular end-systolic stress-volume index ratio in aortic and mitral regurgitation with normal ejection fraction.

To evaluate the left ventricular contractile state in regurgitant valvular disease with normal ejection fraction, we analyzed the end-systolic stress-volume index relationship (ESSVR) by means of cineangiography in 15 normal subjects, 11 patients with aortic regurgitation (AR), and 10 patients with mitral regurgitation (MR) whose ejection fraction (EF) was 60% or more. The end-systolic stress-volume index ratio in normal subjects was 5.57 +/- 0.60 kdyne/cm5/m2 (mean +/- standard deviation), and we defined the range including +/- 2 standard deviations of the ratio as the normal ESSVR range. Six patients with AR and five patients with MR placed inside the normal ESSVR range, termed AR IN and MR IN, but the remaining five patients with AR and MR placed to the right of the normal range, termed AR OUT and MR OUT. EF did not differ between patients with AR IN and AR OUT (69.4 +/- 5.4 verus 70.7 +/- 6.1%) and between MR IN and MR OUT (71.6 +/- 3.6 versus 71.1 +/- 7.9%). The EF of the subdivided groups with AR and MR also did not differ from that of normal subjects (70.7 +/- 7.3%). This finding showed that the left ventricular contractile state was depressed in patients with AR OUT and MR OUT despite a normal EF. In AR and MR the end-systolic stress and end-systolic volume index of OUT did not differ from those of IN, but the end-diastolic volume index of OUT was larger than that of IN (AR OUT 156.8 +/- 27.9 versus AR IN 110.8 +/- 24.1 ml/m2, MR OUT 160.5 +/- 44.7 versus MR IN 101.0 +/ 16.6 ml/m2; both p less than 0.05), and the regurgitant fraction of OUT was higher than that of IN (AR OUT 52.6 +/- 13.6 versus AR IN 29.7 +/- 13.3%, MR OUT 52.9 +/- 10.2 versus MR IN 30.2 +/- 11.4%; both p less than 0.05). In addition, there was a linear inverse correlation between the end-systolic stress-volume index ratio and the end-diastolic volume index in all subjects (r = -0.82, n = 36). In normal subjects there was a linear inverse correlation between end-systolic stress and the EF (r = -0.91, n = 15), but this relationship failed to separate patients with OUT from those with IN. Results of the present study suggest that some patients with AR and MR whose EF was normal had a depressed contractile state, and these patients had a large end-diastolic volume index and a high regurgitant fraction.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1990

Cutaneous nerve-evoked cholinergic inhibition of monosynaptic reflex in the neonatal rat spinal cord: involvement on M2 receptors and tachykininergic primary afferents.

The mechanisms of a cutaneous nerve-evoked inhibition of monosynaptic reflex were investigated in an isolated spinal cord-peripheral nerve preparation of the neonatal rat. Conditioning stimulation of the saphenous nerve, with five pulses at 50 Hz and a strength sufficient to activate C fibers, evoked an inhibition lasting about 20 s of the monosynaptic reflex that was elicited by stimulation of the nerve branch to quadriceps femoris muscle and recorded from the L3 ventral root. This inhibition of monosynaptic reflex was potentiated by an anticholinesterase, edrophonium, and mostly blocked by atropine. Application of acetylcholine, muscarine, bethanechol, carbachol, arecoline and oxotremorine induced an inhibition of monosynaptic reflex. From the effects of muscarinic antagonists, pirenzepine, AF-DX 116, and 4-diphenylacetoxy-N-methylpiperidine on the agonist-evoked and primary afferent-evoked inhibition of monosynaptic reflex it was concluded that the muscarinic receptors involved in the cutaneous nerve-evoked inhibition of monosynaptic reflex are of M2 type. When monosynaptic reflexes were evoked by two successive stimuli with intervals of 15 ms to 1 s, the second response was smaller than the first. This depression of monosynaptic reflex became less pronounced when the reflex was reduced by application of oxotremorine or arecoline or by conditioning stimulation of primary afferents, suggesting that the inhibition of monosynaptic reflex is presynaptic in nature. The late phase of the cutaneous nerve-evoked inhibition of monosynaptic reflex (5-20 s after conditioning stimulation) was markedly depressed by a tachykinin antagonist, spantide. Perfusion of the spinal cord with capsaicin (1 microM) for 1 h also abolished the late phase of the inhibition.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1990

Effects of gangliosides on cell maturation of murine megakaryocytes in a liquid culture system.

Formation of platelet-producing megakaryocytes, the cytoplasm of which showed the terminal stage of cell maturation, heavy granulation and platelet-fields delineated with demarcation membranes, was observed in a short-term culture system, using megakaryocyte-enriched bone marrow cell suspension. Approximately 6-8% of the megakaryocytes changed to the platelet-producing megakaryocytes during 12-hour incubation. In the presence of inhibitors of energy metabolism, formation of the platelet-producing megakaryocytes was inhibited, suggesting that the process is dependent on energy producing systems. Ganglioside GD1a increased both the number of total megakaryocytes and the ratio of the platelet-producing megakaryocytes to total megakaryocytes, while GM1 did not influence the number of total megakaryocytes, but increased the ratio. Gangliosides GM2, GM3 and GD1b showed little effect on either the number of total megakaryocytes or the ratio. The results suggest that ganglioside GD1a stimulates at least two steps of megakaryocyte maturation, the change of megakaryocytic progenitors to megakaryocytes and the subsequent maturation of megakaryocytes to the platelet-producing megakaryocytes, while GM1 stimulates only the latter step of the maturation.

Animals↗
PubMed1990

[The diagnostic value of cine-MR imaging in diseases of great vessels].

The diagnostic value of cine magnetic resonance imaging (cine-MRI) was evaluated in 10 patients with disease of great vessels. The parameters necessary to decide the appropriate treatment, such as presence and extension of intimal flap, DeBakey type classification, identification of the entry, differentiation between true and false lumen, and between thrombosis and slow flow were demonstrated in all patients with dissecting aortic aneurysm. However, abdominal aortic branches could not be demonstrated enough by cine-MRI, therefore conventional AOG was necessary to choose the operative procedure in these cases. In patients with thoracic aortic aneurysm (TAA), cine-MRI was valuable in demonstrating both blood flow and thrombus in the lumen of aneurysm, and AOG was thought to be unnecessary in most cases. Cine-MRI is a promising new technique for the evaluation of diseases of great vessels.

Aged↗