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Biomedical subjects

S Morimoto

Publications and source records attributed to S Morimoto.

At least 397 records · Page 22Linked to original sources

[Citrate as an inhibitor of stone formation--with reference to intestinal citrate absorption and the influence of citrate on intestinal calcium absorption].

The response of serum citrate to the oral citrate load was studied in seven healthy subjects. Serum citrate was significantly elevated from 15 to 60 min post-load with some individual variations. In 27 stone-formers serum citrate and the response to the oral citrate administration was studied and compared with the results obtained on healthy subjects. The serum citrate concentration of stone-formers was 1.99 +/- 0.49 mg/dl as compared to 1.61 +/- 0.35 mg/dl in healthy subjects. After citrate administration serum citrate increased significantly in both groups, but no significant difference was shown in response to the oral citrate load between these two groups (3.44 +/- 0.94 mg/dl in stone-formers, 3.16 +/- 0.38 mg/dl in healthy subjects). In Sprague-Dawley rats each weighing about 200 g urinary citrate and calcium excretion were studied after administration of sodium citrate or calcium chloride or both. The concomitant equimolar administration of sodium citrate and calcium chloride did not have significant influence on urinary citrate or calcium excretion as compared when citrate or calcium was given alone. However, the calcium excretion was significantly decreased with the administration of citrate and calcium ata molar ratio of 1:2.

Animals↗

Phosphoramidon-sensitive endothelin converting enzyme in rat lung.

A neutral proteinase with endothelin (ET)-1 converting activity was identified in cytosol and membrane fractions prepared from rat lung, in a ratio of 1:4, respectively. The membrane-bound proteinase was solubilized by 0.5% 3-[(3-cholamidopropyl) dimethylammonio]-1-propanesulfonate (CHAPS) with an increase in specific activity, and then was characterized. The solubilized proteinase was capable of converting big ET-1 to ET-1 with an optimum pH of 6.5, and the conversion was dose-dependently suppressed by phosphoramidon (IC50 = 0.5 microM). The molecular mass of the proteinase was estimated to be about 500 kDa by gel filtration in the presence of 0.5% CHAPS. These results indicate that rat lung contains a phosphoramidon-sensitive neutral proteinase catalyzing conversion of big ET-1 to ET-1. The proteinase may be involved in the biosynthetic pathway of ET-1 in the lung and/or the conversion of circulating big ET-1.

Animals↗

DNA recognition by synthetic peptides as a model for the dimeric proteins.

A Chiral template possessing a C2 axis has been utilized to study an effect in the dimer formation of oligopeptides. Oligopeptide rich in basic amino acids are used as subunits that would interact with DNA, and the subunits are aligned according to the C2 axis of the template. Synthesis, characterization and DNA binding study of these dimeric peptides will be discussed.

DNA↗

[Skeletal alterations associated with long-term etretinate therapy].

Radiographic skeletal examinations were performed in sixteen adult patients who had received etretinate therapy for various keratinizing disorders (psoriasis vulgaris 13, pustular psoriasis 2, pustulosis palmoplantaris 1) over periods ranging from 0.7 to 4.5 years. The total dose of etretinate ranged from 5.1 to 36.5 g. In these patients, the frequency and the degree of skeletal alterations including hyperostosis, calcification of ligaments and periosteal thickening was found to be higher than that in age- and -sex matched, nontreated controls. Furthermore, almost all of these patients were asymptomatic and revealed no abnormalities in laboratory data, including levels of serum calcium, inorganic phosphate and alkaline phosphatase. It is necessary for patients who are undergoing long-term etretinate therapy to be examined regularly for such skeletal abnormalities.

Adult↗

[Physiological and pathological aging and electrolyte metabolism].

The extracellular and intracellular concentrations of electrolyte were maintained by various systems including kidney and endocrine system. Although concentrations of electrolyte in the extracellular fluid were maintained in normal ranges in healthy elderly subjects, the reserve ability for the maintenance of electrolyte balance decreases with physiological aging. Occurrence of abnormality in electrolyte concentrations in extracellular fluid is thought to be related to pathological aging. The frequency of subjects with abnormal circulating concentrations of electrolytes, as well as abnormal rates of severe such abnormalities increase with age. Clinical characterization and differentiation of physiological and pathological aging are not always easy. On the other hand, the kidney is the central organ for maintenance of electrolyte homeostasis. Decrease in renal ability to retain electrolytes sometimes affect the features of disorders such as hypertension and osteoporosis of elderly subjects. Intravenous infusion of physiological saline at a dose of 20 ml/kg over 2 hr evoked excessive excretion of sodium, calcium and inorganic phosphate in the urine in hypertensive elderly patients and in some patients with senile osteoporosis. These subjects showed decreased levels of plasma renin activity and increased serum levels of parathyroid hormone and 1,25-dihydroxyvitamin D. These features indicate that abnormal renal metabolization of electrolytes involving abnormality of endocrine system may be a cause of, and modulate the clinical features of, some disorders of elderly subjects.

Aged↗

[Plasminogen activator activity and its separative measurement in the gastric mucosa of liver cirrhotics].

Plasminogen activator (PA) activity of the gastric mucosa of liver cirrhotics was measured by use of Glt-Gly-Arg-MCA as the substrate. Gastroduodenal mucosal lesions were more frequently seen in cirrhotic patients with red spot of the gastric mucosa (RS (+) group) as compared to the cases without red spot (RS (-) group). RS (+) group had poor liver function as compared to RS (-) group. PA activity of the gastric mucosa in RS (+) group was higher than RS (-) and control groups. Furthermore, the elevated PA activity was highly associated with severe liver damage estimated by routine liver function test and Child's classification. Separately quantitative assay of PAs was performed by using Lysine-Sepharose 4B chromatography. Both the tissue type and urokinase type PA were higher in the RS (+) group than in control group. These results suggest that accelerated tissue fibrinolytic activity is one of the causative factors of gastric mucosal bleeding in cirrhotic patients with red spot.

Adult↗

[Late postoperative pulmonary vascular resistance in patients with tetralogy of Fallot and pulmonary atresia].

Twenty-two patients with tetralogy of Fallot and pulmonary atresia underwent cardiac catheterization and angiocardiography late after repair. In ten patients, the disease was not associated with the major aortopulmonary collateral artery (MAPCA), but in 12 patients, the disease was associated with it. Three patients died after restudy, two because of pulmonary hypertension and one because of pneumonia. Pulmonary artery mean pressure was 15-92 (28 +/- 21) mmHg, being higher in 75% of the patients with MAPCA than the normal range. The number of pulmonary artery subsegments connected to the central pulmonary arteries was determined from pulmonary arteriography, being 22-42 (38 +/- 6). Pulmonary artery mean pressure and pulmonary vasculature resistance (PVR), 0.8-35.2 (10 +/- 9), inversely correlated with the number of the centrally connected pulmonary artery subsegments (r = -0.81, p less than 0.001 vs PAP, r = -0.85, p less than 0.001 vs PVR). PVR per subsegment also inversely correlated with them (r = -0.81, p less than 0.001). These findings suggest that pulmonary vasculature resistance is abnormally high in this disease, and increase as the number of the centrally connected pulmonary artery subsegments decrease.

Adolescent↗

Sonographic staging of cancer of the mobile tongue.

In order to determine the value of sonography (US), in staging cancer of the mobile tongue, 57 patients were studied prospectively. Real-time sector scanners (5 and 7.5 MHz) were used with a submental approach. The findings by US were compared with those obtained by inspection and palpation and in 13 operated patients with the surgical results. US failed to visualize the tumor in 3 of the 57 patients (5%); in 30 patients (53%), the tumor was considered to be of nearly the same size by US and by palpation, but in 17 cases (30%), to be larger by US than by palpation, and in the remaining 7 cases (12%), to be smaller by US. Extension across the midline (8/8), and depth of tumor penetration, or extension to adjacent structures (5/5) were more correctly evaluated by US. We conclude that US is useful for staging work-up of tumors of the mobile tongue.

Adult↗

[Surgical treatment of tetralogy of Fallot with pulmonary atresia: early and late results].

From 1968 to 1987, 45 consecutive patients with tetralogy of Fallot and pulmonary atresia underwent corrective surgery. In the former 10 years, there were 8 operative deaths (40%) in the 20 patients and no late death. In the recent 10 years, there were 4 operative deaths and 4 late deaths in the 25 patients. In the 17 patients associated with large aorto pulmonary collateral artery (LAPCA) which was ligated in the most patients, there were 5 operative deaths (29%) and 3 late deaths. Nine patients (53%) survived long-term. There were 7 operative deaths (25%), one late death and 20 patients (71%) being long-term survivors in the 28 patients without LAPCA. Pulmonary hemodynamics were investigated in 10 patients without LAPCA and 11 with LAPCA after corrective surgery. Pulmonary arterial mean pressure (PAm) ranged from 9-24 (17 +/- 6) mmHg in patients without LAPCA and 15-92 (37 +/- 23) mmHg in those with LAPCA. Pulmonary arteriography showed arborization abnormality in 7 of the 11 patients with LAPCA. PAm inversely correlated well with number of pulmonary artery segments connected to the central pulmonary arteries. Postoperative pulmonary hypertension was found in patients with less than 16 bronchopulmonary segments connected to the central pulmonary arteries, and two of them died of pulmonary hypertension late after surgery. These results suggested that unifocalization to connect the central pulmonary artery more than 15 bronchopulmonary segments may be an important strategy for correction of this anomaly with LAPCA.

Child↗

Proteolytic processing of porcine big endothelin-1 catalyzed by cathepsin D.

Cathepsin D, a candidate for endothelin-converting enzyme (ECE), was allowed to act on porcine big endothelin-1 (big ET-1, 1-39). The proteinase primarily cleaved the Asp18-Ile19 and Trp21-Val22 bonds of big ET-1(1-39), with a optimum pH of 3.5. The mature ET-1(1-21), generated by the cleavage between Trp21 and Val22, was subsequently degraded by removal of most of the C-terminal tripeptide (Ile19-Ile20-Trp21). Therefore, cathepsin D is by no means a specific ECE, although the proteinase does cleave the Trp21-Val22 bond of big ET-1(1-39) to produce mature ET-1(1-21). The possibility that cathepsin D can act as an endothelin-degrading enzyme in vivo warrants consideration.

Amino Acid Sequence↗

[Erythrocyte sorbitol levels in patients with thyrotoxicosis].

Hyperglycemia and impaired glucose tolerance are frequently observed in patients with hyperthyroidism. However, little is known about whether altered polyol metabolism in hyperthyroidism is present or not. To examine changes in polyol metabolism in hyperthyroidism, we investigated changes in erythrocyte sorbitol, glyceraldehyde reductase (GAR) and sorbitol dehydrogenase (SDH) activities during hyperthyroid and euthyroid states in patients with thyrotoxicosis. Mean levels of erythrocyte sorbitol and GAR were 32.0 +/- 1.6nM/g.Hb and 147.1 +/- 0.3mU/g.Hb, respectively. In thyrotoxic patients in a hyperthyroid state, these values were significantly higher than those in euthyroid controls. Mean level of erythrocyte SDH in thyrotoxic patients was weak but was significantly increased in comparison with that of euthyroid controls. However, mean levels of erythrocyte sorbitol and GAR were remarkably reduced to 23.6 +/- 1.4nM/g.Hb and 125.3 +/- 4.6mU/g.Hb in thyrotoxic patients in a euthyroid state after treatment with anti-thyroid drugs or by subtotal thyroidectomy. Mean level of SDH, on the other hand, was increased after the treatment. In addition, positive correlations were observed between the level of erythrocyte sorbitol or GAR, and the level of free thyroxine(FT4) or free triiodothyronine(FT3). A negative correlation was observed between the level of erythrocyte SDH and the level of FT4 or FT3. These results suggest that the level of erythrocyte sorbitol may be increased through direct acceleration of erythrocyte GAR activity by increased thyroid hormone levels in patients with thyrotoxicosis.

Adult↗

[Case report of a patient with pseudohypoparathyroidism associated with slight increase in serum level of unconjugated bilirubin].

We treated a 29-year-old male patient with pseudohypoparathyroidism type I, who showed a slight increase in serum indirect bilirubin without any signs of liver dysfunction. Serum levels of total, direct and indirect bilirubins were 2.4, 0.7 and 1.7mg/dl, respectively (normal ranges: 0.2-0.8, 0-0.2 and 0.2-0.6mg/dl, respectively). The cause of the increases in serum bilirubin levels was not clear; however, hemolytic anemia, hereditary unconjugated hyperbilirubinemia or ineffective erythropoiesis were ruled out as causes for the increase, since 1) his serum level of haptoglobin was normal, 2) increase in serum level of indirect bilirubin 120 minutes after the infusion of 50mg nicotinic acid was within the normal range, and 3) severe anemia was not observed. Osmotic fragility of his circulating red blood cells was also within normal range. Three other patients with pseudohypoparathyroidism visiting our clinic also showed slightly high levels of serum indirect bilirubin, although four outpatients with idiopathic hypoparathyroidism showed no such abnormality. Abnormality in the responsiveness to parathyroid hormone and/or to that in the cyclic AMP productivity in this disease may cause the increase in the circulating unconjugated bilirubin.

Adult↗

Determination of saposin proteins (sphingolipid activator proteins) in human tissues.

Saposins are small glycoproteins which are required for sphingolipid hydrolysis by lysosomal hydrolases. Each saposin (A, B, C, and D) stimulates a different enzymatic activity. A new simple HPLC method to determine the levels of saposins A, C, and D in tissue was developed. Tissues were homogenized in 20 vol of water, boiled, and centrifuged. The supernatant was lyophilized and redissolved in 5 ml of water. A 1.5-ml sample of the solution was applied to a reverse-phase HPLC column (C4 column) and eluted with an acetonitrile gradient. Most contaminants eluted from the column prior to the saposins, which were eluted later as a cluster of peaks. This cluster was collected and then analyzed by another HPLC system equipped with an AX-300 anion-exchange column using a NaCl gradient. Saposins D, A, and C eluted from the AX-300 column separately and in that order. Quantitation of the saposins was made by measuring the sizes of each peak. Standard curves made from pure saposins showed that quantification was linear over a range from 1 to 5 micrograms. Saposin B was measured by its stimulation activity on pure human liver GM1 ganglioside beta-galactosidase. Stimulation was linear up to 80 micrograms of saposin B. Application of this method to analysis of human tissues for their saposin content is presented.

Chromatography, High Pressure Liquid↗

Conversion of big endothelin-1 to endothelin-1 by two types of metalloproteinases derived from porcine aortic endothelial cells.

Incubation of big endothelin-1 (big ET-1(1-39] with either the cytosolic or membrane fraction obtained from cultured endothelial cells, resulted in an increase in immunoreactive-endothelin (IR-ET), which was markedly inhibited by metal chelators. Phosphoramidon, a metalloproteinase inhibitor, specifically suppressed the membrane fraction-induced increase in IR-ET, whereas the increase in IR-ET observed with the cytosolic fraction was not influenced by phosphoramidon. Reverse-phase (RP)-HPLC of the incubation mixture of big ET-1 with the cytosolic or membrane fraction revealed one major IR-ET component corresponding to the elution position of synthetic ET-1(1-21). Simultaneously, immunoreactivities like the C-terminal fragment (CTF22-39) of big ET-1 were present, as deduced from the RP-HPLC coupled with the radioimmunoassay for CTF. Our results indicate the presence of two types of metalloproteinases, which convert big ET-1 to ET-1 via a single cleavage between Trp21 and Val22, in vascular endothelial cells.

Animals↗

[Usefulness of ioversol (MP-328) in angiocardiography--a multicenter comparative study with iopamidol].

A randomized, controlled study was conducted to compare the radiographic efficacy, safety and usefulness of ioversol and iopamidol in 146 patients undergoing angiocardiography at six institutions. The hemodynamic and electrocardiographic effects were clinically insignificant and comparable for both agents. Ioversol demonstrated lower incidence of adverse reactions and less heat sensation in left coronary arteriography than those with iopamidol. Overall radiographic efficacy with ioversol was slightly better than with iopamidol, according to the evaluation by both investigators and committee members. Ioversol appears to be very useful for angiocardiography. This comparative study demonstrated the value of safety and efficacy evaluation criteria suggested by the preceding clinical trial with ioversol.

Adult↗

Phosphoramidon, a metalloproteinase inhibitor, suppresses the secretion of endothelin-1 from cultured endothelial cells by inhibiting a big endothelin-1 converting enzyme.

Time-dependent secretion of immunoreactive-endothelin (IR-ET) from cultured porcine aortic endothelial cells was markedly suppressed by phosphoramidon is due to proteinase inhibitor. Analysis of the culture supernatant with or without phosphoramidon by reverse-phase high performance liquid chromatography confirmed that the suppression of IR-ET secretion by phosphoramidon is due to a decreae in secretion of endothelin-1-like materials. The secretion of the C-terminal fragment (CTF, 22-39)-like materials of big ET-1 was also decreased by phosphoramidon, whereas there was an increased secretion of big ET-1-like materials. These data strongly suggest that phosphoramidon suppresses the secretion of ET-1 from cultured endothelial cells by inhibiting the conversion of big ET-1 to ET-1. It is most likely that phosphoramidon-sensitive metalloproteinase is responsible for the processing of big ET-1 in vascular endothelial cells.

Animals↗

Mode of cleavage of pig big endothelin-1 by chymotrypsin. Production and degradation of mature endothelin-1.

Pig endothelin-1 [ET-1-(1-21)] seems to be produced via proteolytic processing between Trp-21 and Val-22 of an intermediate form consisting of 39 amino acid residues, termed big ET-1-(1-39), by a chymotrypsin-like proteinase. We examined the chymotryptic-cleavage sites of big ET-1-(1-39) by reverse-phase h.p.l.c. and sequence analysis, and found that chymotrypsin cleaved initially the Tyr-31-Gly-32 bond of big ET-1-(1-39), followed by cleavage between Trp-21 and Val-22. Furthermore, chymotrypsin hydrolysed the generated ET-1-(1-21), producing a single major product that had the same amino acid sequence as ET-1-(1-21) with a cleavage between Tyr-13 and Phe-14. The disulphide bridge between Cys-1 and Cys-15 remained intact. These results indicate that the conversion of big ET-1-(1-39) into ET-1-(1-21) catalysed by chymotrypsin requires hydrolysis of the Tyr-31-Gly-32 bond before that of the Trp-21-Val-22 bond, an event followed by cleavage between Tyr-13 and Phe-14 within the loop of ET-1-(1-21). Thus a chymotrypsin-like proteinase might be involved not only in the production but also in the degradation of ET-1-(1-21) in vivo.

Amino Acid Sequence↗