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Biomedical subjects

S Morimoto

Publications and source records attributed to S Morimoto.

At least 415 records · Page 23Linked to original sources
PubMed1990

Direct inhibition of smooth muscle myosin light chain kinase by arachidonic acid in a purified system.

The direct effect of arachidonic acid (AA) on the phosphorylation of smooth muscle myosin light chain (SMLC) by smooth muscle myosin light chain kinase (SMLCK) was assessed in a purified system. AA inhibited the phosphorylation of SMLC by SMLCK in a dose dependent manner. Increasing the amount of calmodulin (59 nM and 590 nM) did not reverse this inhibition. Linoleic acid and oleic acid also inhibited the phosphorylation. The inhibitory potency of these unsaturated fatty acids paralleled the number of cis double bonds. These results show that SMLCK is directly inhibited by unsaturated fatty acids including AA.

Animals↗
PubMed1990

Phosphoramidon, a metalloproteinase inhibitor, suppresses the hypertensive effect of big endothelin-1.

Intravenous (i.v.) injection of big endothelin-1 (1-39, 0.05-1.0 nmol/kg) to anaesthetized rats produced a dose-dependent and long-lasting hypertensive effect, the magnitude of which was similar to that evoked by ET-1 (1-21). In animals given phosphoramidon (0.25 mg/kg per min i.v.), a metalloproteinase inhibitor, the hypertensive effect of big endothelin-1 was markedly attenuated. The same dose of phosphoramidon did not influence the endothelin-1-induced hypertensive effect. The possibility that big endothelin-1 is converted to endothelin-1 by a phosphoramidon-sensitive metalloproteinase in vivo warrants further attention.

Anesthesia↗
PubMed1990

[Changes in TSH-receptor antibody (TR-AB) and thyroid stimulating antibody (TS-AB) after thyroidectomy in thyrotoxic patients].

Changes in TSH-receptor antibody (TR-Ab) and thyroid stimulating antibody (TS-Ab) after thyroidectomy were examined in seventeen thyrotoxic patients (3 males and 14 females, 40.0 +/- 3.4 yr) with positive TR-Ab and TS-Ab. They were subjected to thyroid surgery because of suspected malignancy, methymazol induced agranulocytosis, cardiac failure, recurrent gastric ulcer or emotional instability. Of these patients, 3 were totally thyroidectomized, 11 were subtotally thyroidectomized and 3 were unilaterally lobectomized. Histological findings in these patients showed diffuse hyperplasia in 8 cases, an adenomatous goiter in 3, diffuse hyperplasia plus follicular adenomas in 5, and Hashitoxicosis in one. Their thyroid function before surgery was as follows: T3 level, 3.9 +/- 0.7 ng/ml; T4, 19.5 +/- 3.3 micrograms/dl; free T3, 11.9 +/- 1.2 pg/ml; free T4, 4.9 +/- 1.0 ng/dl; and TSH, 0.9 +/- 0.1 microU/ml. Mean levels of TR-Ab and TS-Ab before surgery were 56.8 +/- 4.6% and 1,218.6 +/- 262.4%, respectively. Positive anti-thyroid antibody (TGHA) was 47.0%, positive anti-microsomal antibody (MCHA) was 88.2% in these thyrotoxic patients, and mean levels of TGHA and MCHA were 1,688 +/- 715 and 89,280 +/- 34,717 times, respectively. After the operation, these parameters were decreased and their thyroid functions became an euthyroid or a hypothyroid state one month later. The incidence of post-operative hypothyroidism was 45.5% in subtotally thyroidectomized patients, 33.3% in unilaterally lobectomized patients and 100% in totally thyroidectomized patients. TR-Ab levels decreased from 56.2 +/- 6.5% before surgery to 24.5 +/- 12.2% 12 months after surgery, but increased again to 35.0 +/- 15.7% 24 months after surgery in subtotally thyroidectomized patients. These levels also decreased from 50.4 +/- 11.0% before surgery to 37.8 +/- 11.4% 12 months after surgery, and remained unchanged to 38.2 +/- 10.4% 24 months after surgery in unilaterally lobectomized patients. On the other hand, in totally thyroidectomized patients, TR-Ab levels decreased and normalized 12 months after surgery. One of subtotally thyroidectomized or unilaterally lobectomized patients developed recurrent thyrotoxicosis with an increased positive TR-Ab. Mean levels of TS-Ab decreased to 28.3 +/- 181.3% and 152.5 +/- 47.9% 12 and 24 months after surgery, respectively, in subtotally thyroidectomized patients. These levels decreased 12 months after surgery and then increased again to 303.6 +/- 130.6% in unilaterally lobectomized patients. On the other hand, TS-Ab levels decreased and normalized to 94.3 +/- 3.9% 6 months after surgery in totally thyroidectomized patients.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1990

[Preliminary study and clinical evaluation method of ioversol in angiocardiography--establishment of safety evaluation parameters and reliability of radiographic quality evaluation].

A multi-center clinical study of a new nonionic iodinated contrast medium (ioversol) was performed in 26 patients undergoing left ventriculography (LVG) and coronary angiography (CAG) at four centers. The aims of this study were to try to establish a clinical evaluation method on contrast media in angiocardiography and to determine radiographic efficacy and safety of ioversol. The reliability of the method evaluating the radiographic quality of the contrast medium was also examined with statistical analysis. Excellent radiographic efficacy was observed with ioversol and morphological diagnosis was possible in all cases. The electrocardiograms (ST-segment deflection, T-wave amplitude, QT interval, corrected QT interval, arrhythmia and heart rate) and the hemodynamic parameters (left ventricular systolic and end diastolic pressures, left ventricular dp/dt max, aortic systolic and diastolic pressures) indicated no clinically significant changes. This study suggested that the monitoring of the ECGs and hemodynamic parameters for up to three minutes after injection of the contrast medium is sufficient for the evaluation in LVG and CAG, and that the monitoring in CAG during the first injection into each left and right coronary artery is also sufficient for the purpose. Heat sensation during injection was mild. A patient had a symptom of nausea after ioversol administration, but it was mild and transient and resolved spontaneously. There were no abnormal clinical laboratory data related to ioversol. The reliability of the radiographic quality evaluated by the individual clinical investigators was considered to be high and adaptable. However, the evaluation in the blinded cinefilms by the committee members involving all investigators would be more preferable for the higher objectivity. The study results suggest that ioversol is considered to be the efficacious and safe contrast medium for the cardiovascular angiography.

Adolescent↗
PubMed1990

Participation of both intracellular free Ca2+ and protein kinase C in tonic vasoconstriction induced by prostaglandin F2 alpha.

The roles of intracellular free Ca2+ and protein kinase C in the tonic contraction induced by prostaglandin were studied. Prostaglandin F2 alpha induced tonic contraction of rat thoracic aorta in both control and Ca2(+)-free solution. Close correlations were observed between the contractile response of aortic strips and the changes in intracellular free Ca2+ concentration in vascular smooth muscle cells assessed with the fluorescent Ca2+ indicator fura 2, both in control and Ca2(+)-free solutions. Prostaglandin F2 alpha also enhanced the production of inositol 1,4,5-trisphosphate in vascular smooth muscle cells before the rise of the intracellular free Ca2+ concentration. Moreover, 1-(5-isoquinoline-sulfonyl)-2-methylpiperazine, an inhibitor of protein kinase C, inhibited the tonic contractions induced by PGF2 alpha and 12-O-tetradecanoyl phorbol-13-acetate, a direct activator of protein kinase C, at similar concentrations. These results suggest that both intracellular free Ca2+ and protein kinase C participate in prostaglandin F2 alpha-induced tonic contraction.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1990

Increased urinary excretion of beta-hydroxyisovaleric acid in ketotic and non-ketotic type II diabetes mellitus.

To evaluate the catabolism of leucine in diabetes mellitus, the urinary excretion of beta-hydroxyisovaleric acid, a by-product of leucine catabolism, in 21 nonproteinuric type II diabetic patients with and without ketosis and 21 control subjects was measured using gas chromatography-mass spectrometry. Urinary beta-hydroxyisovaleric acid and serum leucine concentrations were higher in the 9 ketotic diabetic patients than in the 12 nonketotic diabetic patients (p less than 0.005, p less than 0.01, respectively) or in the control subjects (p less than 0.01, p less than 0.01, respectively). The serum leucine concentrations in the nonketotic diabetic patients and control subjects did not differ significantly (p greater than 0.05), but urinary beta-hydroxyisovaleric acid concentrations were significantly greater in the former (p less than 0.01). These data suggest that in type II diabetic patients the catabolism of leucine is accelerated even in the absence of ketosis and that the urinary beta-hydroxyisovaleric acid concentration is a useful marker of short-term metabolic control in these patients.

Adult↗
PubMed1990

Evidence for pepstatin-sensitive conversion of porcine big endothelin-1 to endothelin-1 by the endothelial cell extract.

We designed a radioimmunoassay (RIA) specific for the C-terminal fragment (CTF, 22-39) of porcine big endothelin-1 (big ET-1, 1-39), and investigated whether the generation of ET-1 (1-21) is concomitant with that of the CTF during incubation of big ET-1 with the endothelial cell (EC)-extract. When the incubation mixture was applied to reverse-phase high performance liquid chromatography coupled with the RIAs for CTF and ET, immunoreactive (IR)-CTF eluted as one major and one minor peak, and IR-ET as one major peak. The retention times of each peak corresponded to those of synthetic CTF, big ET-1 and ET-1, respectively. An aspartic protease inhibitor pepstatin-A completely inhibited the generation of CTF- and ET-1-like materials. Both materials were also detected in culture medium of porcine aortic ECs. These findings strongly suggest that ET-1 is generated from big ET-1 via a single cleavage between Trp21 and Val22 in vascular ECs and that a pepstatin-sensitive aspartic protease is a possible candidate for big ET-1 converting enzyme.

Animals↗
PubMed1990

Conversion of porcine big endothelin to endothelin by an extract from the porcine aortic endothelial cells.

Conversion of porcine big endothelin (big ET) to endothelin (ET) by an extract from cultured porcine aortic endothelial cells was investigated using a radioimmunoassay (RIA) specific for ET and reverse-phase high performance liquid chromatography (RP-HPLC). When big ET was incubated with the extract at an acid pH in the presence of E-64, a cysteine protease inhibitor, the amount of immunoreactive-ET (IR-ET) in the incubation mixture was greatly increased and the optimum pH for this increased reaction was 4.0. The extract-induced increase in IR-ET was completely inhibited by pepstatin-A. These immunoreactive alterations correlated with those in the vasoconstrictor activity. When the incubation mixture of big ET with the cell extract was applied to the RP-HPLC, the IR-ET eluted at the same retention time as seen with synthetic porcine ET. We suggest that a pepstatin-sensitive aspartic protease is involved in the conversion of big ET to ET in vascular endothelial cells.

Animals↗
PubMed1990

Interaction of saposins, acidic lipids, and glucosylceramidase.

Activity of lysosomal glucosylceramidase is stimulated by two small glycoproteins, saposin A and C, which are, together with two other similar glycoproteins, derived from a single precursor protein. This enzyme is also stimulated by naturally occurring acidic lipids, such as phosphatidylserine and gangliosides. Using highly purified glucosylceramidase, saposins, and acidic lipids, the mechanism of enzyme stimulation was studied by investigating complex formation between the three components and by examining effects on activity caused by changing amounts of saposins and acidic lipids, individually or in combination. The results indicated that acidic lipids form a water-soluble complex with glucosylceramidase but not with saposins and that saposins and acidic lipids each bind to the enzyme at two different sites for the activation. Based on these observations, the previously proposed three-binding sites model of glucosylceramidase, activator, and substrate was modified to one composed of four binding sites: one for carbohydrate of the substrate, one for aglycon, one for acidic lipids, and one for saposins.

Female↗
PubMed1990

[The effect of angiotensin I converting enzyme inhibitor (SQ 14225) on plasma 18-hydroxycorticosterone and aldosterone in sodium depleted conscious rats].

Altered sodium intake is known to cause a greater change in plasma 18-hydroxycorticosterone (18-OHB) level than in plasma aldosterone level, resulting in an increase of plasma 18-OHB/aldosterone ratio in sodium-depleted man and rats. To evaluate the role of endogenous angiotensin II in the high plasma 18-OHB/aldosterone ratio in sodium-depleted rats, we examined the effect of the angiotensin I converting enzyme inhibitor SQ 14225 on plasma 18-OHB and aldosterone in sodium-depleted (SD) and sodium-repleted (SR) conscious rats. Plasma renin activity (PRA) and plasma angiotensin II were higher in the SD rats than in the SR rats. The ingestion of SQ 14225 caused an increase in PRA and a decrease in plasma angiotensin II, whereas these changes were more prominent in the SD rats than in the SR rats. Plasma 18-OHB and aldosterone levels were higher in the SD rats than in the SR rats. The plasma 18-OHB/aldosterone ratio was also higher in the SD rats than in the SR rats. The ingestion of SQ 14225 caused decreases in plasma 18-OHB and aldosterone levels in both the SR and SD rats, whereas the SQ 14225-induced decreases in plasma 18-OHB and aldosterone levels were more prominent in the SD rats than in the SR rats. Thus, the ingestion of SQ 14225 induced a decrease in the plasma 18-OHB/aldosterone ratio in both the SR and SD rats. The decrease in plasma 18-OHB/aldosterone ratio was more prominent in the SD rats than in the SR rats.(ABSTRACT TRUNCATED AT 250 WORDS)

18-Hydroxycorticosterone↗
PubMed1990

Pepsin, an aspartic protease, converts porcine big endothelin to 21-residue endothelin.

Porcine big endothelin (big ET-39) at 1 nM, a concentration with no influence on contractile activity in isolated rat aorta, induced a slow-onset and sustained contraction by the pre-incubation with pepsin. When the incubation mixture of big ET-39 with pepsin was analyzed by high-performance liquid chromatography on an octadecyl silica column, two major products of pepsin hydrolysis were obtained; their amino acid sequences were identical with those of 21-residue endothelin (ET-21) and a C-terminal peptide of big ET-39, big ET (22-39), respectively. On the other hand, no degradation of ET-21 was observed by pepsin treatment. These results indicate that pepsin specifically cleaves a Trp21-Val22 bond in the big ET-39 molecule, producing ET-21 and big ET (22-39). Thus, the possibility that pepsin-like aspartic protease may participate in the conversion of big ET-39 to ET-21 in vivo warrants further attention.

Animals↗
PubMed1990

Differentiation between left circumflex and right coronary artery occlusions: studies on ST-segment deviation during percutaneous transluminal coronary angioplasty.

To distinguish between acute occlusion of the right coronary artery (RCA) and the left circumflex artery (LCx) by electrocardiography, we studied ST-segment deviation during balloon inflation in percutaneous transluminal angioplasty. The composite electrocardiographic criteria based on ST-segment deviations increased the diagnostic specificity: that is, the finding of inferior infarction (ST-segment elevation in leads II, III, aVF) without lateral infarction (ST-segment elevation in leads V5,6) was highly suggestive of RCA occlusion (sensitivity and specificity: 35 of 43 cases, 81.4%; and 33 of 36 cases, 91.7%), whereas ST-segment elevation in leads V5,6 (LCx: 23 of 36 cases; 63.9%, RCA: 5 of 43 cases; 11.6%) or isolated ST-segment depression in leads V2-4 (LCx: 9 of 36 cases; 25.0%, RCA: none of 43 cases) was highly suggestive of LCx occlusion. These results indicate that the composite electrocardiographic criteria were useful in predicting the artery involved in acute myocardial infarction, although any single criterion was not sensitive or specific enough to differentiate right from left circumflex coronary artery occlusion.

Angioplasty, Balloon, Coronary↗
PubMed1990

Lesions in side branches of arteries having undergone percutaneous transluminal coronary angioplasty: a histopathologic study.

Percutaneous transluminal coronary angioplasty (PTCA) may cause occlusion in side branches. No histologic studies, however, have been made on side branches of the arteries in which PTCA has been performed. A histologic study was therefore made to explain the effect of PTCA on side branches. Histologic specimens were prepared by serial step sectioning from 15 side branches of 10 autopsied cases that had undergone PTCA. The results of examination by light microscope were as follows: (1) Stenoses due to PTCA were seen in seven branches (46.7%). (2) The stenoses were classified into three types: (a) stenosis due to blocking of the orifice of a side branch by the disrupted portion of the intima of the main artery (one branch); (b) stenosis due to medial dissection of the main artery or further dissection occurring even in the side branches (three branches); and (c) stenosis due to fragmentation of the internal elastic lamina of the main artery accompanied by proliferation of smooth muscle cells even in the side branch (three branches). It is now clear that stenosis is caused in side branches long after PTCA. Extra care is required when major side branches exist in the portion where this procedure is to be performed.

Adult↗
PubMed1990

Effects of 1,25-dihydroxyvitamin D3 on the syntheses of DNA and glycosaminoglycans by rat aortic smooth muscle cells in vitro.

Studies were made on the effects of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] on the syntheses of DNA and glycosaminoglycans (GAG) by rat aortic smooth muscle cells (SMC) in vitro. DNA synthesis in cell cultures without fetal calf serum (FCS) was stimulated by incubation for 24 hr with 1,25-(OH)2D3 at concentrations of more than 10(-12) M, stimulation being maximal at a concentration of 10(-8) M. On the other hand, GAG synthesis was inhibited dose-dependently by 1,25-(OH)2D3 at concentrations of more than 10(-11) M. Other vitamin D3 metabolites had similar, but weaker effects on the syntheses of DNA and GAG by SMC, which were proportional to their affinities for the 1,25-(OH)2D3 receptor. These effects of 1,25-(OH)2D3 were not seen after short-term incubation (1 hr). These findings suggested that 1,25-(OH)2D3 stimulated the proliferation of SMC independent of growth factors in FCS, and that its effects were dependent on its specific receptor. Excess 1,25-(OH)2D3 might cause arteriosclerosis not only by stimulating proliferation but also by suppressing GAG synthesis.

Animals↗
PubMed1990

Inverse relation between severity of psoriasis and serum 1,25-dihydroxy-vitamin D level.

The serum levels of calcium, inorganic phosphate, parathyroid hormone, calcitonin, 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D were measured in 34 patients with psoriasis vulgaris and compared with the severity of skin lesions. Severity of psoriasis was evaluated by three indices, the area-severity index (ASI), the area index (AI) and the severity index (SI), determined as the product of the area and severity, the area, and the severity of the individual skin lesions, respectively. The mean basal levels of these serum parameters were within the normal range. ASI and SI showed significant inverse correlations (r = -0.387, P less than 0.05 and r = -0.638, P less than 0.01, respectively) with the serum level of 1,25-dihydroxyvitamin D, but not with any other serum parameters, but AI was not correlated with any of these serum parameters. These data suggest that psoriatic patients are not deficient in 1,25-dihydroxyvitamin D, but that development of this skin disease may be related to a slightly decreased level of active metabolites of vitamin D or abnormalities in the responsiveness of the skin cells to them.

Adolescent↗
PubMed1990

Characterization of a mutation in a family with saposin B deficiency: a glycosylation site defect.

Saposins are small, heat-stable glycoproteins required for the hydrolysis of sphingolipids by specific lysosomal hydrolases. Saposins A, B, C, and D are derived by proteolytic processing from a single precursor protein named prosaposin. Saposin B, previously known as SAP-1 and sulfatide activator, stimulates the hydrolysis of a wide variety of substrates including cerebroside sulfate, GM1 ganglioside, and globotriaosylceramide by arylsulfatase A, acid beta-galactosidase, and alpha-galactosidase, respectively. Human saposin B deficiency, transmitted as an autosomal recessive trait, results in tissue accumulation of cerebroside sulfate and a clinical picture resembling metachromatic leukodystrophy (activator-deficient metachromatic leukodystrophy). We have examined transformed lymphoblasts from the initially reported saposin B-deficient patient and found normal amounts of saposins A, C, and D. After preparing first-strand cDNA from lymphoblast total RNA, we used the polymerase chain reaction to amplify the prosaposin cDNA. The patient's mRNA differed from the normal sequence by only one C----T transition in the 23rd codon of saposin B, resulting in a threonine to isoleucine amino acid substitution. An affected male sibling has the same mutation as the proband and their heterozygous mother carries both the normal and mutant sequences, providing additional evidence that this base change is the disease-causing mutation. This base change results in the replacement of a polar amino acid (threonine) with a nonpolar amino acid (isoleucine) and, more importantly, eliminates the glycosylation signal in this activator protein. One explanation for the deficiency of saposin B in this disease is that the mutation may increase the degradation of saposin B by exposing a potential proteolytic cleavage site (arginine) two amino acids to the amino-terminal side of the glycosylation site when the carbohydrate side chain is absent.

Amino Acid Sequence↗
PubMed1990

Distribution of saposin proteins (sphingolipid activator proteins) in lysosomal storage and other diseases.

Saposins (A, B, C, and D) are small glycoproteins required for the hydrolysis of sphingolipids by specific lysosomal hydrolases. Concentrations of these saposins in brain, liver, and spleen from normal humans as well as patients with lysosomal storage disease were determined. A quantitative HPLC method was used for saposin A, C, and D and a stimulation assay was used for saposin B. In normal tissues, saposin D was the most abundant of the four saposins. Massive accumulations of saposins, especially saposin A (about 80-fold increase over normal), were found in brain of patients with Tay-Sachs disease or infantile Sandhoff disease. In spleen of adult patients with Gaucher disease, saposin A and D accumulations (60- and 17-fold, respectively, over normal) were higher than that of saposin C (about 16-fold over normal). Similar massive accumulations of saposins A and D were found in liver of patients with fucosidosis (about 70- and 20-fold, respectively, over normal). Saposin D was the primary saposin stored in the liver of a patient with Niemann-Pick disease (about 30-fold over normal). Moderate increases of saposins B and D were found in a patient with GM1 gangliosidosis. Normal or near normal levels of all saposins were found in patients with Krabbe disease, metachromatic leukodystrophy, Fabry disease, adrenoleukodystrophy, I-cell disease, mucopolysaccharidosis types 2 and 3B, or Jansky-Bielschowsky disease. The implications of the storage of saposins in these diseases are discussed.

Adult↗