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Biomedical subjects

S Fukuyama

Publications and source records attributed to S Fukuyama.

At least 55 records · Page 3Linked to original sources
PubMed1995

Close correlation between nitric oxide (NO) formation from NO releasers and the biological activities of these agents in rats.

The aim of this study was to clarify the difference in the profiles of nitric oxide (NO) formation of three NO releasers and to examine the correlation between NO formation from these drugs and their biological activities in rats. (+/-)-(E)-ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexenamide (FK409) and 3-morpholinosydnonimine (SIN-1) spontaneously generated nitrite, an oxidative product of NO, in sodium phosphate buffer (PB) solution. On the other hand, sodium nitroprusside (SNP) did not generate nitrite. The rank order of the concentrations of nitrite generated was SIN-1 > FK409 >> SNP. In biological studies using rats, these drugs showed anti-platelet effects and in vitro vasorelaxant and hypotensive effects with potencies in the rank order of FK409 > SIN-1 > SNP and SNP > FK409 > SIN-1, respectively. These drugs generated nitrite with concentrations in the rank order of FK409 > SIN-1 > SNP and SNP > FK409 > SIN-1 in rat plasma and in PB solution with L-cysteine (Cys), respectively. In conclusion, three NO releasers liberate NO with NO-releasing rates of different rank orders under different incubation conditions, and the anti-platelet effects and vasorelaxant and hypotensive effects of these NO releasers closely correlate with NO formation from the compounds in the plasma and PB solution with Cys, respectively, but not with that in PB solution without Cys.

Animals↗
PubMed1995

A new nitric oxide (NO) releaser: spontaneous NO release from FK409.

The remarkable vasorelaxant and anti-platelet effects of FK409 have been reported to be due to nitric oxide (NO) release. The purpose of the present study is to investigate the spontaneous NO-releasing pathway of FK409 in aqueous solutions. 1H-NMR spectra of FK409 suggested that the compound underwent a time-dependent elimination of the hydrogen atom at alpha-position of the nitro moiety (at the 5-position) in weakly alkaline solutions. In addition, the degradation of FK409 monitored by HPLC showed a pH-dependency accelerating with an increase of pH. These results revealed that the first step in the degradation of FK409 might be the hydroxyl ion-dependent subtraction of the hydrogen atom at the 5-position. On the other hand, NO release from FK409 also exhibited a pH-dependency, and the velocity of NO liberation was markedly enhanced above pH 6. Furthermore, a linear relationship between the rate of FK409 degradation and that of NO formation was observed, indicating that the rate-limiting step for NO formation is the same as that for degradation. Thus, the rate-limiting process of NO formation from FK409 is due to the deprotonation reaction of the hydrogen atom at the 5-position by hydroxyl ions. The deprotonation process appears to be an essential step for both FK409 degradation and NO release. On the basis of the results, a possible kinetic scheme for NO release from FK409 is proposed.

Buffers↗
PubMed1995

The effect of mechanical stress on hypertrophy of the lumbar ligamentum flavum.

To clarify the effect of mechanical stress on hypertrophy of the ligamentum flavum (LF), we compared the thicknesses, histological findings, and total collagen content of 161 lumbar LF in two groups defined by radiographic signs. LF with one or more signs of spondylolisthesis, disk degeneration, vacuum phenomenon, traction spur, or facet joint osteoarthrosis were considered degenerative; all others were considered nondegenerative. Thickness was measured by computed tomographic scan, and total collagen content by Woessner's method. We found that the ligament was thicker in the degenerative group (4.0 +/- 1.1 mm vs. 3.0 +/- 0.7 mm, p < 0.01), the degeneration of fibers more severe, and the total collagen content higher (51.9 +/- 14.5% vs. 40.3 +/- 3.9%, p < 0.05). Thus, mechanical stress is considered a cause of ligament hypertrophy.

Adolescent↗
PubMed1994

Mechanism of optical isomerization of (S)-N-[1-(2-fluorophenyl)-3,4,6,7- tetrahydro-4-oxopyrrolo[3,2,1-jk] [1,4]-benzodiazepine-3-yl]-1H- indole-2-carboxamide (FK480) in soft capsules containing polyethylene glycol 400 and glycerol.

FK480 is a new synthetic non-peptide antagonist of cholecystokinin (CCK)-A receptors. The dosage form of FK480 is a soft capsule containing a solution of FK480 in a mixture of polyethylene glycol 400 (PEG 400) and glycerol to improve its bioavailability. Studies on the stability of this FK480 dosage form revealed that the main degradation occurred by optical isomerization at the asymmetric C-3 position of the pyrrolobenzodiazepine ring. The degradation reaction was accelerated by formic acid formed in a mixture of PEG 400 and glycerol. Addition of amino acids to the capsule solution retarded the isomerization by reacting with formic acid. Therefore, formic acid appears to accelerate optical isomerization of FK480.

Benzodiazepinones↗
PubMed1994

[Spontaneous regression of lumbar hernia of the nucleus pulposus. Follow-up study of 4 cases by repeated magnetic resonance imaging].

INTRODUCTION: As yet there have been no consistent magnetic resonance (MR) imaging studies on spontaneous regression of herniated lumbar nucleus pulposus (HNP). We present four patients in whom follow-up MRI images demonstrated spontaneous regression or complete disappearance of a herniated lumbar nucleus pulposus. One patient presented with a large extruded type, and the rest had the sequestrated type. All patients made evolved favorably with conservative therapy. RESULTS: Follow-up MRI images revealed a remarkable regression of the HNP in the extrusion case and complete disappearance in the sequestration cases. In the extrusion case, follow-up MRI images showed rapid shrinkage of the portion extruded into the epidural space. In the sequestration cases, MR images with Gadolinium DTPA (enhanced MR images) showed that the enhanced lesion around the HNP had reduced its size as the HNP diminished. Final MR images could not detect the HNP in any view of the spinal canal. CONCLUSION: We therefore concluded that the regression of HNP in MR images might have been due more to resorption than to dehydration.

Adult↗
PubMed1993

Induction of mucosal disease in cattle persistently infected with noncytopathic bovine viral diarrhea-mucosal disease virus by superinfection with cytopathic bovine viral diarrhea-mucosal disease virus.

Three head of cattle persistently infected with noncytopathic bovine viral diarrhea-mucosal disease virus (ncBVD-MDV) were superinfected naturally or experimentally with cytopathic bovine viral diarrhea-mucosal disease virus (cBVD-MDV). In the naturally superinfected case, one animal manifested pyrexia and severe diarrhea, and died without developing antibodies to cBVD-MDV. However, another animal survived with only continual slight anorexia and pyrexia, and developed strong resistance to the superinfected strain. In the experimental cases, induction of MD was unsuccessful in two persistently infected cattle when superinfected with cBVD-MDV antigenically heterologous for persistently infected ncBVD-MDV. They also developed antibodies to the cBVD-MDV strain with which they had been infected. After 6 months, these cattle were infected again with a cBVD-MDV strain different from that used in the previous experiment. One animal infected with this strain, which was antigenically homologous to the persistently infected strain, died after developing MD symptoms without developing antibodies to the infecting strain. It is suggested that the antigenic relationship between the persistent ncBVD-MDV and the superinfected cBVD-MDV was an important factor in developing MD.

Animals↗
PubMed1993

Protection against bovine leukemia virus infection by use of inactivated vaccines in cattle.

The protective effects of vaccines made from the viral materials of LK15 cell line (LK15 vaccine) or bat lung cell line (Bat2cl1; Bat vaccine) infected with bovine leukemia virus (BLV) were examined in cattle. Twelve cattle were vaccinated twice at 4-week interval then challenged 4 weeks after the second inoculation. Nine cattle vaccinated with the LK15 vaccine produced antibody to BLV-specific glycoprotein (gp), and the titers ranged from 1:16 to 1:64 by the agar gel immunodiffusion test. Four cattle challenged with 100 microliters (70 to 100 syncytia) of cow blood persistently infected with BLV were protected from infection. However, of the remaining 5 cattle challenged with 500 microliters of infected blood, only 2 were protected. Of the three cattle vaccinated with the Bat vaccine, gp antibody titers ranged from 1:8 to 1:64. Two of them were protected against the challenge with 100 microliters of infected blood. Two cattle protected against the challenge were rechallenged 32 weeks after the first vaccination and not protected. On the other hand, 2 animals protected against the challenge were revaccinated with the LK15 vaccine 32 weeks after the first vaccination. They protected against rechallenge. The results show that all cattle which had gp antibody titers of 1:16 or above were protective against challenge with 100 microliters of the infected blood.

Animals↗
PubMed1993

[The changes in Ca(2+)-sensitivity of rabbit skeletal myofibrillar ATPase activity under various conditions].

Effect of the composition of the reaction mixture on the Ca(2+)-sensitivity of myofibrillar ATPase of rabbit skeletal muscle was investigated. The Ca(2+)-concentrations necessary for the half maximum ATPase activation were 2.95 x 10(-6) M at 50 mM KCl, 4.37 x 10(-6) M at 90 mM KCl and 5.25 x 10(-6) M at 130 mM KCl. Thus the Ca(2+)-sensitivity was definitely lower at higher KCl concentrations. The Ca(2+)-sensitivity was about 2 times higher at pH 7.3 (pCa50 5.65) compared to the Ca(2+)-sensitivity at pH 6.8 (pCa50 5.36). The change in the Mg-ATP concentration between 0.5 mM and 3.5 mM, did not significantly affect the Ca(2+)-sensitivity of myofibrillar ATPase, but affected biphasically the maximum ATPase activity. These change in the Ca(2+)-sensitivity at various conditions is considered to be due mainly to the property of troponin C, the Ca(2+)-receptive protein of myofibrils.

Adenosine Triphosphatases↗
PubMed1992

Fragmentation hemolysis in a patient with hypertrophic obstructive cardiomyopathy and mitral valve prolapse.

We encountered a 65-year-old female with hypertrophic obstructive cardiomyopathy and mitral valve prolapse who had infective endocarditis and hemolytic anemia. The infecting organism of endocarditis was group A streptococci. With regard to the etiology of the hemolytic anemia, fragmentation hemolysis was considered because fragmented red cells and elevated lactic dehydrogenase were observed. Haptoglobin was markedly decreased. Coombs' test, Ham's test and abnormal hemoglobin were negative. She had not had a hemolytic attack in the past. Ultrasonic cardiography showed asymmetrical septal hypertrophy, mitral valve prolapse and 285 mmHg of calculated pressure gradient in the left ventricle. Cardiac catheterization showed 115 mmHg of left intraventricular pressure gradient and mitral regurgitation (grade 2). Hemolysis was slightly improved after treatment with propranolol. Thus, fragmentation of the normal red cells seemed to be due to shear stress.

Aged↗
PubMed1992

Field trials on a live bovine respiratory syncytial virus vaccine in calves.

Field trials were carried out in calves using a live bovine respiratory syncytial (BRS) virus vaccine prepared from the attenuated BRS virus, strain rs-52. Two hundred seventy-five and 353 calves were vaccinated intranasally and intramuscularly, respectively. No undesirable postvaccinal reactions were observed in the vaccinated calves. Of the serum neutralizing (SN) antibody negative calves 89.7% (26/29) and 92.8% (90/97) developed SN antibody 1 month after intranasal and intramuscular vaccination, respectively. Most of the calves having SN antibody titers of 1:1 or 1:2 at the time of vaccination showed a significant increase in SN antibody titer. About 70% and 90% of the calves vaccinated intranasally and intramuscularly, respectively, maintained SN antibody for 6 months after vaccination. In a field trial, a natural BRS virus infection occurred about 5 months after the start of the trial. Ten of the 16 unvaccinated control calves showed respiratory symptoms due to BRS virus infection. On the contrary, all of the 68 vaccinated calves exhibited no symptoms at all, indicating efficacy of the vaccine.

Animals↗
PubMed1990

Establishment of an attenuated strain of bovine respiratory syncytial virus for live virus vaccine.

To develop a live virus vaccine for the prevention of bovine respiratory syncytial (BRS) virus infection in calves, an attempt was made to produce an attenuated virus. The RS-52 strain of BRS virus, isolated from the nasal secretions of a naturally infected calf, was subjected to serial passages in adult hamster lung established (HAL) cells at 30 degrees C and the attenuated rs-52 strain as a live virus vaccine was established. The rs-52 strain multiplied better at 30 degrees C than at 34 or 37 degrees C in HAL cells. The differences in the highest virus titers of this strain between the culture temperature of 30 degrees C and that of 34 or 37 degrees C were more than 2.25 log TCID50. Colostrum-deprived newborn calves and 2 approximately 4 months old calves inoculated with the rs-52 strain manifested no abnormal clinical sings at all. However, all inoculated calves produced serum neutralization antibody. When the colostrum-deprived newborn calves immunized with the rs-52 strain were challenged with the virulent NMK7 strain of BRS virus, they exhibited no pyrexia or other abnormal clinical signs at all. An attempt was made to recover the virus from nasal secretions of these calves, but in vain. On the other hand, a nonimmunized control colostrum-deprived newborn calf developed slight fever, mild cough, and slight serous nasal discharge after challenge exposure. The virus was recovered from nasal secretions of this calf. From these results, it was considered that the rs-52 strain could be used as an attenuated live virus vaccine for prevention of BRS virus infection.

Animals↗
PubMed1989

The renal kallikrein-kinin system in renoparenchymal hypertension.

In order to investigate the pathophysiological role of renal kallikrein (KK)-kinin system in renoparenchymal hypertension (RHT), urinary excretion of KK was measured in 15 patients with RHT and compared with that in 16 normotensive subjects (NT). The urinary kininase excretion was also determined in some subjects. KK quantity and activity was measured by direct radioimmunoassay and kininogenase assay, respectively. Kininase activity was determined as a bradykinin-degradating activity. The urinary excretion of KK quantity and activity as well as the fractional excretion of KK were significantly lower in RHT than in NT. Significantly positive correlations were observed between urinary excretion of KK quantity or KK activity and creatinine clearance. The fractional excretion of kininase was significantly higher in RHT than in NT while no significant difference was found in the urinary kininase excretion between these groups. These results suggest that renal KK-kinin system is suppressed not only in the whole kidney but in each nephrone which is still functioning, and the suppression of this system may contribute to the pathophysiology of RHT.

Adult↗
PubMed1989

Renal kininases in primary aldosteronism.

In order to further clarify the role of renal kallikrein-kinin (K-K) system in primary aldosteronism (PA), daily urinary excretions of renal K-K system components including kallikrein (KAL), kinin (KIN), total kininase (K-ase), K-ase I, K-ase II and neutral endopeptidase (NEP) were measured in PA and normotensives (NT). In this study, a new method for the simultaneous determination of human urinary K-ase I, II and NEP was established and employed. The daily excretions of KAL was significantly higher in PA than that in NT, while no difference was found in KIN between PA and NT. On the other hand, total K-ase in PA (897 +/- 258 micrograms/min/day) was significantly higher than that in NT (209 +/- 6). NEP was also significantly higher in PA (262 +/- 22 micrograms/min/day) than that in NT (127 +/- 6), whereas there were no differences in K-ase I and K-ase II between PA and NT. The relative contributions of K-ase I, II and NEP to total K-ase in NT were 14, 27 and 59%, while those in PA were 12, 17 and 36%, respectively. As a result, these three K-ase contributed only 64% to the total K-ase in PA. These findings suggested that 1) NEP may play a major role in the catabolism of renal KIN in human, 2) NEP is accelerated in PA, 3) unknown K-ase, different from K-ase I, II or NEP, may exist in PA, and 4) accelerated renal K-ase activity may play some role on the disorder of renal water-sodium metabolism and high blood pressure in PA.

Humans↗
PubMed1989

A sensitive method for differential determination of kininase I, II and neutral endopeptidase (NEP) in human urine.

In order to clarify the significance of NEP in human renal kallikrein-kinin system, an assay system was developed for the simultaneous determination of kininase I, II and NEP activities in human. Each kininase activity was determined by measuring the hydrolysis of bradykinin in the presence of specific inhibitors of kininase I (2-mercaptomethyl-3-guanidinoethylthiopropanoic acid), kininase II (captopril) and NEP (phosphoramidon) in 8 normal subjects. The effects of the different assay buffers on kininase activities were also investigated by using a phosphate buffer. Total kininase, kininase I, II and NEP activities were 499 +/- 65 ng/min/ml (mean +/- S.E.), 55 +/- 8, 141 +/- 21 and 299 +/- 42, respectively in our method using a tris buffer, while a phosphate buffer brought about activities of 358 +/- 43, 45 +/- 5, 156 +/- 21 and 135 +/- 25 ng/min/ml. The relative contributions of kininase I, II and NEP to total kininase activity were 11, 29 and 59% in our assay system, while they were 13, 44 and 35% when a phosphate buffer was used. From these results it was suggested that 1) phosphate may inhibit urinary NEP activity, so that a tris buffer should be used as the incubation buffer, 2) NEP is the major component of human urinary kininases, and 3) NEP may play an important role in the renal kallikrein-kinin system.

Buffers↗
PubMed1989

Localization of neutral endopeptidase in the kidney determined by the stop-flow method.

Recently, the existence of neutral endopeptidase (NEP) as a new kininase in the kidney has been reported. In this study, the localization of NEP in the nephron was investigated and compared with other components of the renal kallikrein-kinin (K-K) system by using a stop-flow method in dog kidneys. The stop-flow method was performed according to the procedures previously reported by Scicli et al and Malvin et al. Five mongrel dogs (weighing 15-20 kg) were used in this study. Kininase I, II and NEP were measured by the modified procedure of Ura et al. Kallikrein and kinin were found in the distal tubules, and kininase I and II were observed in both the distal and proximal tubules. NEP was localized mainly in the proximal tubules. A small peak was also recognized in the distal tubules. From these results, it was suggested that, not only kininase I and II but also NEP existing in the proximal tubules may destroy kinin filtered from the glomeruli, and these kininases existing in the distal tubules may play an important role in connection with kinin producing enzymes on the regulation of activity in the renal kallikrein-kinin system.

Animals↗
PubMed1989

High homology between 6-aminohexanoate-cyclic-dimer hydrolases of Flavobacterium and Pseudomonas strains.

The nucleotide sequences of the genes for 6-aminohexanoate-cyclic-dimer hydrolases of Flavobacterium sp. strain K172 (F-nylA) and Pseudomonas sp. NK87 (P-nylA), enzymes essential for the degradation of a by-product of the nylon-6 industry, were obtained by the dideoxynucleotide chain-termination method. A 1,479-base-pair open reading frame starting at a GTG and terminating at a TGA was found for the both of the genes. The P-nylA and F-nylA genes encoded polypeptides of 493 amino acids and had only 10 base substitutions in the coding region, which caused seven amino acid substitutions.

Amidohydrolases↗