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Biomedical subjects

Y Imai

Publications and source records attributed to Y Imai.

At least 685 records · Page 38Linked to original sources

Dihydrolipoic acid protects pancreatic islet cells from inflammatory attack.

In vitro models of pancreatic islet cell inflammation are the lysis of isolated islet cells by activated macrophages or by oxygen radicals released by the endothelial enzyme xanthine oxidase. Dihydrolipoic acid protected islet cells in both systems by different modes of action. Macrophage cytotoxicity towards islet cells, which is nitric-oxide-mediated, was suppressed by 2 h of preincubation of macrophages with lipoic acid. Similarly, 2 h of preincubation sufficed to protect islet cells against enzymatically produced oxygen radicals. Dihydrolipoic acid was found by chemiluminescence assay to scavenge directly such radicals. In macrophages dihydrolipoic acid suppressed the production of nitrite as a measure of nitric oxide release. These results suggest that dihydrolipoic acid is an anti-inflammatory agent which at the same time interferes with nitric oxide release from inflammatory macrophages and protects target cells from oxygen radical attack.

Animals↗

Rhythmic oscillations of blood pressure and R-R interval in patients with chronic renal failure.

Rhythmic blood pressure (BP) and R-R interval (R-R) oscillations at low-, mid- and high-frequency bands (LF: 0.02-0.06 Hz; MF: 0.07-0.14 Hz; HF: 0.15-0.40 Hz) were compared between uraemic patients maintained on haemodialysis and control subjects. The LF and MF power spectra of BP were attenuated more in patients than in controls. With subjects standing, the MF power spectrum of BP increased significantly in both groups. With subjects supine, the plasma norepinephrine concentration was higher, and its increment upon standing was greater in patients than in controls. Each R-R frequency power spectrum decreased more in patients than in control subjects. The HF power spectrum of R-R, i.e. a vagal tone index, systematically decreased upon standing in the control subjects but not in the patients. The linear coupling between BP and R-R oscillations was strongest in the HF band, decreasing in the MF and LF bands. Transfer function analysis indicated that, in uraemic patients, linear BP/R-R relationships were altered in the HF band but remained normal in the LF and MF bands. The present results suggest that, first, the decreased amplitude of Mayer waves, i.e. the MF power spectrum of BP, observed in uraemic patients can be attributed to low sensitivity of the vasculature to sympathetic stimuli, and, secondly, autonomic modulation of linear BP/R-R relationships is frequency-dependent.

Adult↗

A case of chronic pancreatitis complicated by massive pericardial and right pleural effusion.

A 42-year-old man was admitted complaining of dyspnea. Chest X-ray showed an increase in cardiac size, and echocardiography revealed a large volume of pericardial effusion. Pancreatic enzyme levels were elevated in both serum and pericardial effusion. Computed tomography and endoscopic retrograde pancreatography demonstrated a fistula connecting a pancreatic pseudocyst with the pericardium and the right pleural cavity. Massive pericardial and right pleural effusion is an extremely rare complication of chronic pancreatitis. In this case, computed tomography and endoscopic retrograde pancreatography were useful for diagnosing the fistula.

Adult↗

Intraorbital arteriovenous malformation: case report.

A case of intraorbital arteriovenous malformation presenting with visual loss, exophthalmos, and chemosis of the right eye is reported. Enhanced computer tomography and magnetic resonance imaging showed extraocular muscle enlargement and vascular abnormality in the right retrobulbar space. Angiography revealed an abnormal intraorbital vascular stain with an extremely dilated right ophthalmic artery. Total removal of the intraorbital contents was performed after unsuccessful endovascular and surgical treatment of arteriovenous malformation (AVM). Histopathological examination disclosed an AVM in the retrobulbar fatty tissue with extension into the extraocular muscles and optic nerve.

Adult↗

Bond strength of resin to dentin treated with calcium phosphate desensitizer.

In a previous study we proposed a new method utilizing immediate precipitation of calcium phosphate (CaP) in situ for treatment of dentin hypersensitivity. Sequential application of 5% disodium phosphate followed by 10% calcium chloride on patent dentin surface resulted in instant occlusion of dentin tubules and immediate relief from the hypersensitivity. To guarantee long-lasting effectiveness of the CaP treatment, resin coverage of the treated dentin surface will be the next practical approach. However, the CaP covering the surface may possibly affect bonding of resins. This study determined the effect of the CaP treatment on tensile bond strength of adhesive resins to dentin. Independent of the type of resin used, a bond strength of 4-5 MPa was obtained; cohesive failure occurred within the resin-CaP hybridized composite layer rather than at the dentin surface. The CaP treatment produced a significant increase in the bond strength of one resin.

Animals↗

Balloon angioplasty for postoperative pulmonary artery stenosis in transposition of the great arteries.

OBJECTIVES: This study was designed to assess the success rate and determinants of success or failure of balloon angioplasty for postoperative pulmonary stenosis in patients with transposition of the great arteries. BACKGROUND: Previous reports have suggested that pulmonary stenosis that develops after the arterial switch operation is not likely to be dilated. METHODS: Twenty-eight patients with transposition of the great arteries underwent 39 balloon angioplasty procedures after the arterial switch operation. The mean age at dilation was 4.5 +/- 2.2 years (range 0.7 to 9.8), and the interval between operation and balloon dilation was 3.6 +/- 1.8 years. The criterion of successful dilation was a > or = 50% increase in predilation diameter or a > or = 50% decrease in predilation pressure gradient. If the right ventricular/aortic pressure ratio decreased by > or = 0.2, so that the ratio became < 0.68, reoperation was thought to be not indicated. RESULTS: The success rate of balloon angioplasty for pulmonary artery stenosis was 51% (20 of 39 dilations). The mean age at dilation in the group with successful dilation (3.6 years) was significantly younger than that in the group with unsuccessful dilation (5.4 years). The interval between operation and dilation in the successful dilation group (2.4 years) was significantly less than that in the unsuccessful dilation group (4.6 years). In 13 patients who underwent balloon angioplasty < 3.5 years after operation, balloon dilation was successful in 92%. The balloon/artery ratio was significantly greater in the successful than in the unsuccessful dilation group. A right ventricular/aortic pressure ratio > or = 0.68 was observed in 20 patients, and reoperation was not indicated in 10 patients (50%). There was no death, but one pulmonary artery rupture that did not require surgical intervention occurred. Aneurysmal dilation of the pulmonary artery was observed in three patients. CONCLUSIONS: These data indicate that although the success rate of balloon angioplasty for pulmonary artery stenosis after the arterial switch operation is low (approximately 50%), balloon angioplasty can be the first therapeutic choice owing to the low complication rate and the potential benefit of the procedure. The success rate can be high if angioplasty is performed < 3.5 years after operation and a balloon of adequate size is used.

Age Factors↗

Plasma concentrations of immunoreactive-endothelin in patients with chronic renal failure treated with recombinant human erythropoietin.

1. Elevation of blood pressure is one of the major side effects of recombinant human erythropoietin therapy in haemodialysis patients. 2. We investigated the possible involvement of endothelin in the pathogenesis of this recombinant human erythropoietin-induced blood pressure elevation in 51 patients undergoing maintenance haemodialysis. 3. Blood haemoglobin level increased from 7.1 +/- 0.1 to 8.8 +/- 0.1 g/dl (means +/- SEM) after 8 weeks of treatment with recombinant human erythropoietin (3000-4500 units/week). An increase in mean blood pressure was found in 19 patients (37%) (n = 9, by 0-10 mmHg; n = 10, by > 10 mmHg). 4. Plasma immunoreactive-endothelin concentration significantly increased from 2.26 +/- 0.18 to 3.14 +/- 0.31 pmol/l in the 10 patients whose mean blood pressure increased by more than 10 mmHg (P < 0.05), but not in the other patients. Moreover, the increase in plasma immunoreactive-endothelin concentration showed a significant positive correlation with the change in mean blood pressure in 19 patients with elevated mean blood pressure (r = 0.47, P < 0.05). 5. There was no significant correlation between the change in plasma immunoreactive-endothelin concentration and the change in blood haemoglobin level or the change in body weight. 6. These results suggest the possibility that endothelin may contribute to the recombinant human erythropoietin-related rise in blood pressure in some haemodialysis patients.

Blood Pressure↗

Hypotensive effect of losartan, a nonpeptide angiotensin II receptor antagonist, in essential hypertension.

We examined the chronic effects of losartan (DuP 753), a novel orally active angiotensin II receptor antagonist, on blood pressure and renal function in eight hospitalized patients with essential hypertension. After a control period of 1 week, losartan was administered orally once a day for 2 to 4 weeks in increasing doses of 12.5, 25, 50, and 100 mg, until blood pressure in the supine position decreased more than 20 mm Hg (systolic) and 10 mm Hg (diastolic) (or 13 mm Hg in mean blood pressure). The average dose of losartan was 59.4 +/- 43.7 (mean +/- SD) mg/day. Systolic, diastolic, and mean blood pressures, according to 24 h monitoring, fell significantly, from 151.9 +/- 6.8 to 137.2 +/- 7.9 mm Hg, from 90.6 +/- 3.7 to 81.0 +/- 3.7 mm Hg, and from 111.1 +/- 4.6 to 99.7 +/- 5.0 mm Hg, respectively (mean +/- SE, P < .01 for each), with no change in circadian rhythm or variability of blood pressure. Reduction in blood pressure was slightly greater during daytime than during sleep time. Unlike peptide angiotensin II antagonists, losartan did not exert pressor action. No significant alterations were observed in body weight, serum electrolytes, creatinine clearance, urine volume, or urinary excretion of sodium. Losartan significantly lowered serum uric acid concentration from 5.5 +/- 0.4 to 4.8 +/- 0.3 mg/dL (P < .05). Urinary excretion of uric acid increased significantly from 498.9 +/- 64.4 to 540.6 +/- 66.6 mg/day (P < .05). Plasma renin activity rose significantly but plasma aldosterone concentration did not change with the losartan treatment. These results suggest that losartan has a long-acting hypotensive effect with a hypouricemic action in essential hypertension.

Adult↗

Age-specific characteristics of nocturnal blood pressure in a general population in a community of northern Japan.

The age- and gender-specific profile of circadian blood pressure variation was examined by monitoring ambulatory blood pressure (ABP) in 477 untreated subjects in a rural community of northern Japan. Autoregressive spectral analysis demonstrated three major peaks at around 24, 12, and 8 h. We fitted a truncated Fourier series with three harmonics to the blood pressure (BP) data using least squares regression. More than half of the BP and pulse rate periodic curves were bimodal, one-third were trimodal, and the remainder were unimodal. The nadir of BP appeared between 00:00 and 01:30, and that of pulse rate occurred between 00:30 and 02:00. The nadir of systolic and diastolic BP, as well as pulse rate, appeared earlier with increasing age, and the difference between subjects in their 20s and those in their 70s was about 1 h. The amplitude of 24 h BP decreased with increasing age in men, but not in women. This type of information on the circadian BP profile of a general population is useful for the diagnosis and treatment of hypertension.

Adult↗

Replacement of Thr-303 of P450 2E1 with serine modifies the regioselectivity of its fatty acid hydroxylase activity.

Threonine-303 of rabbit P450 2E1, which is putatively located at the distal heme surface, was replaced by serine and valine via site-directed mutagenesis. In the oxidized state, the Ser-mutated P450 exhibited a low- and high-spin mixed-type (low > high) absorption spectrum, whereas the Val-mutated P450, like the wild-type P450, exhibited a nearly high-spin type spectrum. The reduced CO complexes of the Ser- and Val-mutated P450s, as well as that of the wild-type P450, showed a Soret absorption maximum at 452 nm. Both mutated P450s were active in the hydroxylation of C10 to C18 fatty acids at somewhat lower rates than the wild-type P450. The Val-mutated P450 gave the same two products (the major one is probably the omega-1 hydroxy analog) as the wild-type P450, while additional products were formed on incubation with C11 to C17 fatty acids as substrates of the Ser-mutated P450; a total of four products was detected for each of the C12 to C15 fatty acids, and three for each of the C11, C16, and C17 homologues. The metabolites of laurate were determined by GC-MS analysis to be the omega-1, omega-2, omega-3, and omega-4 hydroxy counterparts. The Ser-mutated P450 hydroxylated drug substrates at almost the same rates as the wild-type P450, while the mutation to valine significantly lowered the drug hydroxylase activities.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Importance of successive prolines in the carboxy-terminal region of P450 2C2 and P450 2C14 for the hydroxylase activities.

Proline-480 and proline-481 are highly conserved in the P450 2 family. When these successive prolines of P450 2C2 were replaced by Ala-Thr, its activities of laurate (omega-1)-hydroxylation and benzphetamine N-demethylation were lost. On the other hand, the mutated P450 which retained one of the proline residues was 60-100% active in the (omega-1)-hydroxylation and 100-120% active in the N-demethylation. Pro-Pro (480, 481) to Ala-Thr mutated P450 2C14 was also inactive in testosterone 16 alpha-hydroxylation and benzphetamine N-demethylation, the activities of the wild-type P450 2C14. In the carboxyterminal region of the P450 2C subfamily, the sequence of P450 2C2 from residues 469-473 is noticeably different from those of the other members of this subfamily. The Ser-473 to Val mutation of P450 2C2 caused a decrease in the (omega-1)-hydroxylase activity to one-fifth but the N-demethylase activity was not much affected. When the sequence of P450 2C2 from residues 469-473 was replaced by that of P450 2C14 (mutation at four residues), the 16 alpha-hydroxylase and N-demethylase activities were increased by seven- and three-fold, respectively, and the (omega-1)-hydroxylase activity was decreased to one-third. The mutated P450 2C2, in which the carboxy-terminal four residue sequence or the proline cluster adjacent to the amino-terminal membrane-anchor signal sequences was deleted, was not accumulated in yeast cells transformed with plasmids directing the synthesis of such P450s.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

Purification and characterization of a form of P450 from horse liver microsomes.

A form of P450 [termed P450(h-1)] was purified from the liver microsomes of a male horse to electrophoretic homogeneity. The specific content of the final P450(h-1) preparation was 14.8 nmol/mg of protein and the recovery was 0.38% of the microsomal P450. The apparent molecular weight of P450(h-1) was 52,000 Da. The absorption spectra of P450(h-1) indicated that P450(h-1) was a low- and high-spin mixed type P450 in the oxidized form. The reconstituted system containing P450(h-1) could catalyze benzphetamine N-demethylation, 7-ethoxycoumarin O-deethylation, and testosterone 16 alpha-hydroxylation. In the horse hepatic microsomes, aniline p-hydroxylation and testosterone 6 beta-hydroxylation, in addition to the above reactions, were detected. The N-terminal amino acid sequence of P450(h-1) was highly homologous to that of rat P450 2C11. Western blot analysis using anti-P450(h-1) antibody revealed that this antibody most strongly recognized P450 2C13 among ten rat P450s belonging to eight different subfamilies involved in hepatic drug metabolism. This anti-P450(h-1) antibody inhibited the testosterone 16 alpha-hydroxylase activity in horse liver microsomes. These results suggest that P450(h-1) belongs to the P450 2C subfamily and contributes to the testosterone 16 alpha-hydroxylation in horse liver microsomes.

Amino Acid Sequence↗

Dynamics and participation of type II phospholipase A2 in rat zymosan-induced pleurisy.

Intrapleural injection of zymosan into rats induces acute inflammation characterized by plasma leakage and cellular influx. The level of type II phospholipase A2 (PLA2) increased in the pleural fluid as well as in exudating leukocytes after the injection of zymosan. Rather low PLA2 activity was found in cell lysates, though treatment of such lysates at low pH increased the PLA2 activity drastically. The appearance of "acid-extracted" PLA2 activity in leukocytes preceded that of the extracellular enzyme activity, suggesting that pleural leukocytes might be one of the origins of the extracellular enzyme. Treatment of exudating pleural leukocytes with purified rat type II PLA2 elicited the production of prostaglandin E2, but not platelet-activating factor appreciably. These findings indicate that type II PLA2 might play a role in the progression of inflammation through the production of eicosanoids in the present inflammation model.

Animals↗

Characteristics of a community-based distribution of home blood pressure in Ohasama in northern Japan.

OBJECTIVE: To evaluate the distribution, reference values and day-to-day variation of blood pressure of untreated subjects measured at home. DESIGN: Cross-sectional study of a cohort. SETTING: General community in northern Japan. SUBJECTS: Blood pressure was measured in 871 subjects (mean +/- SD age 46.0 +/- 19.5 years, range 7-98, constituting 38.7% of the local population of Uchikawama region, Ohasama) who were not receiving antihypertensive medication. METHODS: Subjects measured their own blood pressure at home at least three times (mean +/- SD 19.7 +/- 8.4) each morning using a semi-automatic oscillometric blood pressure measuring device. Screening blood pressure was measured once. MAIN OUTCOME MEASURES: Distribution of home blood pressure in the study population as a whole and with respect to age and sex, and the distribution of day-to-day variation of home blood pressure were determined. RESULTS: Mean home blood pressure was 117.3 +/- 13.4/69.3 +/- 9.7 mmHg (95% confidence interval 116.4-118.2/68.7-70.0). The 95th centile value was 143/85 mmHg, mean+SD 131/79 mmHg and mean + 2SD 144/89 mmHg. Mean screening blood pressure was 126.2 +/- 18.9/72.1 +/- 11.7 mmHg (95th centile 159/92 mmHg). Age- and sex-specific 95th centile values as well as mean +/- SD were obtained. Mean+SD, mean + 2SD and the 95th centile values obtained as reference upper limits of home blood pressure from subjects identified as normotensive by screening blood pressure (n = 707) were 125/77, 137/86 and 134/83 mmHg, respectively. Home blood pressure increased gradually with increasing age in both men and women, although blood pressure was significantly higher in men until 50 years of age. Day-to-day variation of home systolic blood pressure also increased with age. CONCLUSION: Since the distribution of home blood pressure values was affected by age and sex, age- and sex-matched reference values for home blood pressure should be established. Home blood pressure values in elderly subjects should be evaluated carefully, since these exhibit greater day-to-day variation.

Adolescent↗

Molecular breeding of a biotin-hyperproducing Serratia marcescens strain.

We previously reported that an acidomycin-resistant mutant of Serratia marcescens Sr41, SB304, and a mutant that was derived from SB304 and was resistant to a higher concentration of acidomycin, SB412, produced 5 and 20 mg of D-biotin, respectively, per liter of a medium containing sucrose and urea (N. Sakurai, Y. Imai, M. Masuda, S. Komatsubara, and T. Tosa, Appl. Environ. Microbiol. 59:2857-2863, 1993). In order to increase the productivity of D-biotin, the biotin (bio) operons were cloned from strains SB412, SB304, and 8000 (wild-type strain), and pLGM412, pLGM304, and pLGW101, respectively, were obtained through subcloning. These plasmids harbored 7.2-kb DNA fragments coding for the bioABFCD genes on a low-copy-number vector and were introduced into SB304, SB412, and 8000. Among the resulting recombinant strains, SB412(pLGM304) exhibited the highest D-biotin production (200 mg/liter) in the production medium. The plasmid was stably maintained in cells. Unexpectedly, SB412(pLGM412) grew very slowly, and the D-biotin productivity of this recombinant strain was not evaluated because pLGM412 was unstable.

Biotin↗

Construction of a Biotin-Overproducing Strain of Serratia marcescens.

We have isolated mutants resistant to acidomycin, a biotin analog, from Serratia marcescens Sr41. Strain SB304, resistant to 0.5 mg of acidomycin (frequently called actithiazic acid) per ml, produced 5 mg of d-biotin per liter of a medium containing sucrose and urea. Strain SB412, which was isolated from SB304 on a minimal agar plate containing 2 mg of acidomycin per ml and 0.1 mg of 5-(2-thienyl)-valeric acid per ml, produced 20 mg of d-biotin per ml. The two enzymes related to biotin synthesis were found to be released from biotin-mediated feedback repression in these mutants. Transductional analysis revealed that SB412 had acquired at least two mutations, one in the biotin operon locus and the other in an unknown locus distant from the biotin operon locus.

Journal Article↗