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Biomedical subjects

S Okuda

Publications and source records attributed to S Okuda.

At least 73 records · Page 4Linked to original sources
PubMed1998

Chronic inhibition of nitric oxide in central nervous system does not cause hypertension.

Acute inhibition of nitric oxide (NO) synthase in the brain causes elevation of blood pressure and sympathetic excitation under anesthetized conditions. To investigate chronic effects of NO synthase inhibition in the central nervous system on blood pressure regulation in conscious unrestrained animals, we administered NG-monomethyl-L-arginine (L-NMMA), a potent NO synthase inhibitor, at low (22.5 mumol/kg) and high (67.5 mumol/kg) doses for 1 wk into the cisterna magna with an osmotic pump and measured mean arterial pressure (MAP) and heart rate (HR) by a telemetry method. The same dose of NG-monomethyl-D-arginine (D-NMMA), an inactive isomer of L-NMMA, was administered to control rats. Chronic intracisternal administration of low-dose L-NMMA significantly decreased the brain nitrite/nitrate and NO metabolite contents as compared with D-NMMA (p < 0.05). However, MAP and its variability, HR and its variability, and plasma norepinephrine levels did not differ between the two groups of rats at either low- or high-dose treatment. Thus, chronic NO synthase inhibition in the central nervous system did not affect systemic hemodynamics or plasma norepinephrine concentrations despite the inhibition of brain NO. Our results suggest that endogenous NO in the central nervous system, at least as a whole, may not affect the systemic hemodynamics of chronic unanesthetized rats.

Animals↗
PubMed1998

Fatal liver cirrhosis and esophageal variceal hemorrhage in a patient with type IIIa glycogen storage disease.

A 45-year-old woman with type IIIa glycogen storage disease (GSD IIIa) died of variceal hemorrhage secondary to liver cirrhosis. The postmortem examination disclosed increased intracellular glycogen in the liver as well as in the heart and skeletal muscle. Although most liver injuries in GSD IIIa have been considered to be non-progressive in adulthood, liver cirrhosis can be a cause of death in some patients.

Diagnosis, Differential↗
PubMed1998

[Continuous arterial infusion of protease inhibitor with supplementary therapy for the patients with severe acute pancreatitis--clinical effect of arterial injection of ulinastatin].

We treated five patients with severe acute pancreatitis by continuous arterial infusion (CAI) of protease inhibitor, nafamostat mesilate. Arterial injection (AI) of ulinastatin was performed in four cases and AI of antibiotics (IPM/CS) was done in one case, as supplemental therapies of CAI. Abdominal pain disappeared in 7.9 hours on the average, abdominal tenderness disappeared in 5.0 days and laboratory data lately recovered. All five cases treated by these therapies were cured without hemodialysis or surgical treatment in acute phase. AI of ulinastatin through arterial infusion catheter is pharmacokinetically more effective, because it yields a relatively high concentration of the drug at the acting site when compared with that of intravenous injection. Furthermore ulinastatin inhibits different types of protease from nafamostat mesilate. Therefore the clinical effect of CAI of nafamostat mesilate is enhanced by the combined therapy with AI of ulinastatin. It is also suggested that arterial injection of ulinastatin might be effective for the control of abdominal pain and that arterial injection of antibiotics might have an advantage on prevention of infectious pancreatic necrosis.

Acute Disease↗
PubMed1998

[A severe case of acute autonomic and sensory neuropathy].

Acute autonomic and sensory neuropathy (AASN) is a rare neuropathy characterized by acute autonomic dysfunction and objective sensory disturbances. A 26-year-old pregnant woman with severe autonomic and sensory dysfunction is reported. This patient suddenly developed marked nausea and vomitting in about 2 days after having a sore throat. She then developed signs of autonomic dysfunction including dilated non-reactive pupils, dryness of the eyes and oral mucous membranes, generalized anhidrosis, paralytic ileus, orthostatic hypotension, and continuous tachycardia. She also had severe generalized sensory impairments of all modalities, and all deep tendon reflexes were absent. Sensation was almost totally lost for all modalities below the neck. There was marked pseudoathetosis and sensory ataxia in all extremities. Motor examination was normal. She had inability to urinate. At this time she was 38 weeks pregnant, and when she showed signs of fetal distress, a Caesarean section was performed. Albumino-cytological dissociation was seen in the CSF. Serum noradrenaline was reduced, no sensory nerve action potentials could be elicited, and reduced coefficient of variation of the R-R interval on electrocardiography was observed. Plasma exchange was performed every other day for 3 days for about 3 weeks after the onset of the illness, but no favorable effects. Seven months after the onset, her autonomic dysfunction slightly improved, but there was no recovery from the sensory disturbances. Many symptoms and signs that characterize AASN occurred in this patient, and each was severe. The patient developed SIADH, sleep apnea, personality change, and amenorrhea in the course of the disease. We suggest that AASN patients might have both peripheral and central nervous system manifestations including seizures and personality changes.

Acute Disease↗
PubMed1997

Relationship between brainstem MRI and pathological findings in progressive supranuclear palsy--study in autopsy cases.

The relationship between the features of MRI in brainstem and pathological findings was investigated in eight autopsy cases with progressive supranuclear palsy (PSP). Features of T1-weighted images at midbrain level were atrophy of tegmentum and tectum, and dilatation of aqueduct. Histologically, these findings were consistent with atrophy of periaqueductal gray matter, quadrigeminal plate, and tegmentum. In these lesions, we detected neuronal loss, decrease in density of myelinated fibers, gliosis, rarefaction of tissues, and tau-positive structures such as neurofibrillary tangles (NFTs), glial fibrillary tangles (GFTs) and neuropil threads. At pons level, atrophy of tegmentum, atrophy of pontine base, and dilatation of prepontine cistern were found. Tau-positive structures were observed not only in tegmentum but also in pontine base. The density of the tau-positive structure was closely related to the severity of atrophy. Features of T2-weighted images were high intensity in the periaqueductal lesion and tegmentum in pons. In these lesions, severe histological findings were detected. The MRI features in brainstem were closely related to the histological findings as PSP.

Aged↗
PubMed1997

Stent placement for recurrent vasospastic angina resistant to medical treatment.

The successful stent placement for treatment of recurrent vasospastic angina in a patient with nonstenotic coronary arteries is described. Use of the Palmaz-Schatz stent resulted in successful vasodilation that completely prevented anginal attacks. This procedure represents an alternative treatment for patients with vasospastic angina refractory to aggressive medical therapy.

Angina Pectoris, Variant↗
PubMed1997

Studies on 3'-quaternary ammonium cephalosporins--III. Synthesis and antibacterial activity of 3'-(3-aminopyrazolium) cephalosporins.

The synthesis and in vitro antibacterial activity of 7 beta-[(Z)-2-(2-aminothiazol-4-yl)-2-methoxyiminoacetamido]cephalos porins bearing N-mono or dialkyl and carbamoyl aminopyrazolium, and five- or six-membered rings fused to the 3-aminopyrazolium methyl groups at the 3-position, are described. Aminopyrazolium methyl cephalosporins (23e, f, i), with fused saturated and unsaturated rings were especially effective against Staphylococcus strains compared to 3-amino-2-methylpyrazolium methyl cephalosporin (1). Among the cephalosporins prepared in this work, 7 beta-[(Z)-2-(2-aminothiazol-4-yl)-2-methoxyiminoacetamido]-3-(4,5, 6, 7-tetrahydro-1-pyrazolo[1,5-a]pyrimidinio)methyl-3-cephem-4-carbox ylate (23f) showed a good balance of antibacterial activity against both Gram-positive bacteria including Staphylococcus aureus and Gram-negative bacteria including P. aeruginosa. An imidazopyrazolium group at the 3-position in, for example, cephalosporin (23i) was particularly effective for improving antibacterial activity against MRSA.

Cephalosporins↗
PubMed1997

Studies on 3'-quaternary ammonium cephalosporins--IV. Synthesis and antibacterial activity of 3'-(2-alkyl-3-aminopyrazolium) cephalosporins related to FK037.

The synthesis and in vitro antibacterial activity of 7 beta-[(Z)-2-(2-aminothiazol-4-yl)-2-methoxyiminoacetamido] cephalosporins bearing various 2-alkyl-3-aminopyrazolium groups at the 3-position are described. Antibacterial activity against MRSA was affected by the nature of the substituent at the 2-position on the 3'-aminopyrazolium groups. Among the cephalosporins prepared in this study, 7 beta-[(Z)-2-(2-aminothiazol-4-yl)-2-methoxyiminoacetamido]-3-[3-am ino-2-(2 -hydroxyethyl)-pyrazolio]methyl-3-cephem-4-carboxylate sulfate (23e, FK037) showed extremely potent broad-spectrum activity against both Gram-positive bacteria including MRSA, and Gram-negative bacteria including Pseudomonas aeruginosa. In particular, the in vivo activity against MRSA of FK037 was the highest of all the beta-lactam antibiotics tested.

Anti-Bacterial Agents↗
PubMed1997

Sudden death in chronic dialysis patients.

METHODS: Causes of sudden death were investigated in 113 chronic dialysis patients who died during the 10-year period from July 1979 to January 1989; postmortem examination was performed on 93 of the cases (autopsy rate; 82.3%). Sudden death was regarded as death 24 h after the onset of acute illness in patients without any restriction in their daily activities. There were 35 sudden death cases out of the 93 autopsied chronic dialysis patients. We analysed the causes of sudden death for all chronic dialysis patients and for those who died suddenly. RESULTS: The mean age of the 93 cases was 61.4 +/- 10.5 years (+/-SD). Stroke was the most frequent cause of death (24 cases, 25.8%) in the 93 autopsied cases. This was followed by cardiac disease in 18 (19.4%), infectious disease in 16 (17.2%), malignancy in 14 (15.1%), and dissecting aortic aneurysm in 5 (5.4%). The mean age of the 35 sudden death cases was 60.9 +/- 10.9 years. Of the 35 sudden death cases in chronic dialysis patients, dissecting aortic aneurysm was the most common cause of sudden death (5 cases, 14.3%), followed by cerebral haemorrhage in three (8.6%), acute subdural haematoma in three (8.6%), acute myocardial infarction in two (5.7%), cerebral infarction in two (5.7%), and subarachnoidal haemorrhage in one (2.9%). CONCLUSIONS: Dissecting aortic aneurysm, leading frequently to stroke as a cause of sudden death in chronic dialysis patients, at least in Japan, should be carefully differentiated from other cardiac diseases in chronic dialysis patients, such as severe atherosclerosis.

Adult↗
PubMed1997

Formation of multimers of cucumber mosaic virus satellite RNA.

Double-stranded RNA multimers of cucumber mosaic virus (CMV) satellite RNA were detected in CMV-infected plants. RT-PCR showed that plus-sense and minus-sense monomers and plus-sense multimers of satellite RNA were present. Multimeric minus-sense RNA was not present except in the form of multimeric dsRNA. Sequence analysis of 52 cloned junction regions in head-to-tail repeats of unit-length satellite RNA indicated that about 35% of the junction sequences were precise fusions of monomer units, 56% lacked sequence of the 5' component, and 10% lacked sequence of both 3' and 5' components. No junction contained additional nucleotides. Deletions at the junction regions may have accumulated during CMV multiplication in inoculated plants. These data suggest that replicase is not released from the template during synthesis of multimeric molecules of satellite RNA.

Base Sequence↗
PubMed1997

Regulation of inducible nitric oxide synthase expression in L6 rat skeletal muscle cells.

Cytokine-stimulated expression of inducible type of nitric oxide synthase (iNOS) seems to be regulated by various signal pathways in a cell-specific manner. In this study, we examined how it was regulated in L6 rat skeletal muscle cells. In L6 cells, the combination of interleukin-1 beta and interferon-gamma induced a marked accumulation of nitrite, a stable metabolite of nitric oxide. In parallel with this reaction, iNOS mRNA expression was achieved at a maximum between 3 and 6 h, and iNOS protein was detectable at 6 h and peaked at 24 h after stimulation. Tyrosine kinase inhibitors, herbimycin A, and genistein suppressed cytokine-induced iNOS expression and nitrite production. Forskolin, an adenosine 3',5'-cyclic monophosphate-dependent protein kinase (PKA) activator, and phorbol 12-myristate 13-acetate, a protein kinase C (PKC)-activating phorbol ester, enhanced these cytokine-induced reactions. These results indicate that iNOS expression by cytokines is mediated via a protein tyrosine kinase-dependent pathway and is positively modulated by both PKA- and PKC-dependent pathways in this cell type.

Animals↗
PubMed1997

Roles of TGF-beta and latent TGF-beta-binding protein in glomerulosclerosis induced by two consecutive injections of monoclonal antibody 1-22-3 in rats.

The present study demonstrated the elevated synthesis and gene expressions of transforming growth factor beta (TGF-beta) or latent TGF-beta binding protein (LTBP) in an irreversible glomerulosclerosis rat model induced by two consecutive injections of monoclonal antibody (MoAb) 1-22-3. The rats were intravenously injected with 500 microg of MoAb 1-22-3 either once or twice at an interval of 2 weeks. The rats were sacrificed at 24 h, 1 week, 2 weeks or 16 weeks after the last injection. At 24 h, the mesangiolytic changes in the rats with two injections of MoAb 1-22-3 were similar to those in the rats with one injection. The glomerular matrix score in the rats with two injections was significantly higher than that in the rats with one injection at weeks 1, 2 or 16. An increased LTBP localization in the glomeruli of the rats at week 1 after either one or two injections was detected in the segmentally expanded mesangial matrix. Moreover, LTBP in the glomeruli of rats at week 1 after two injections appeared to be more strongly stained in the enlarged mesangial matrix than that in the rats after one injection. A TGF-beta bioassay using mink lung epithelial cells revealed that the total TGF-beta in the glomerular culture conditioned medium in the rats at week 1 after two injections was significantly larger than that in the rats after one injection. A Northern blotting analysis of the glomeruli showed that both the expressions of TGF-beta and LTBP mRNA in the rats after two injections were higher than those in the rats after one injection. These findings suggested that the elevated TGF-beta or LTBP may thus be related to the irreversible glomerulosclerosis that was induced by two injections of MoAb 1-22-3 into rats.

Animals↗
PubMed1997

Asymmetrical dimethylarginine, an endogenous nitric oxide synthase inhibitor, in experimental hypertension.

NG,NG-dimethyl-L-arginine (ADMA) is an endogenously synthesized nitric oxide (NO) synthase inhibitor which has potent pressor/vasoconstrictor effects. Dimethylargininase metabolizes ADMA to L-citrulline and plays a key role in determining the in vivo levels of ADMA. To investigate the role of ADMA in the pathogenesis of hypertension, we measured 24-hour urinary excretion of ADMA (UADMA) and nitrate/nitrite (NOx) in Dahl salt-sensitive hypertensive rats and spontaneously hypertensive rats (SHR). In Dahl salt-resistant rats, high-salt diet (8% NaCl) did not increase blood pressure and increased urinary NOx (P < .01) without changes in UADMA compared with low-salt diet (0.3% NaCl). In contrast, in Dahl salt-sensitive rats, high-salt diet increased blood pressure (P < .01), did not change urinary NOx excretion, and increased UADMA (P < .01). There was a significant (r = .65, P < .01) correlation between UADMA and the level of blood pressure in Dahl salt-sensitive rats. Plasma levels of NOx and ADMA and renal dimethylargininase content were comparable among them. These results may suggest that in Dahl salt-resistant rats, blood pressure is kept constant during high-salt intake, possibly due to the compensatory increased production of NO, and that in Dahl salt-sensitive rats, high-salt intake increases the production of ADMA, attenuates the compensatory increases in NO, and increases blood pressure. These results also suggest that the systemic production of ADMA is not dependent on renal dimethylargininase. SHR had significantly greater urinary NOx excretion (P < .05) and smaller UADMA than Wistar-Kyoto rats (P < .05), and UADMA was inversely correlated with their mean arterial pressure (r =.64, P < .05). In conclusion. ADMA, independently of the renal dimethylargininase content, may play a role in the pathogenesis in Dahl salt-sensitive hypertensive rats but not in SHR.

Amidohydrolases↗
PubMed1997

Dose-dependent incorporation of tea catechins, (-)-epigallocatechin-3-gallate and (-)-epigallocatechin, into human plasma.

Tea catechins, (-)-epigallocatechin-3-gallate (EGCg) and (-)-epigallocatechin (EGC), have been reported to suppress oxidation of plasma low density lipoprotein (LDL) in vitro. If dietary catechins can be efficiently incorporated into human blood plasma, anti-atherosclerotic effects in preventing oxidative modification of LDL would be expected. In this study, a newly developed chemiluminescence detection-high pressure liquid chromatography (CL-HPLC) method for measuring plasma catechins was used and the incorporation of EGCg and EGC into human plasma was investigated. Healthy subjects orally ingested 3, 5, or 7 capsules of green tea extract (corresponding to 225, 375, and 525 mg EGCg and 7.5, 12.5, and 17.5 mg EGC, respectively). The plasma EGCg and EGC concentrations before the administration were all below the detection limit (< 2 pmol/ml), but 90 min after, significantly and dose-dependently increased to 657, 4300, and 4410 pmol EGCg/ml, and 35, 144, and 255 pmol EGC/ml, in the subjects who received 3, 5, and 7 capsules, respectively. Both EGCg and EGC levels detected in plasma corresponded to 0.2-2.0% of the ingested amount. Catechin intake had no effect on the basal level of endogenous antioxidants (alpha-tocopherol, beta-carotene, and lycopene) or of lipids in plasma. These results suggested that drinking green tea daily would contribute to maintain plasma catechin levels sufficient to exert antioxidant activity against oxidative modification of lipoproteins in blood circulation systems.

Adult↗
PubMed1997

Effectiveness of aldose reductase inhibitors for diabetic gastroenteropathy with constipation.

We present a diabetic patient with long-standing constipation complicated by paralytic ileus and septic shock. She successfully recovered from a critical condition, and her diabetes was well controlled. However, the constipation did not improve even after the administration of conventional medications. Epalrestat, an aldose reductase inhibitor (ARI), improved her bowel motility and autonomic cardiovascular dysfunction, as evident from her heart rate and blood pressure response. Gastroenteropathy is a major diabetic complication which may cause disturbed bowel motility leading to serious enterobacterial infections, thus, its amelioration is important. ARI may be beneficial in the treatment of diabetic gastroenteropathy refractory to conventional therapies.

Aldehyde Reductase↗
PubMed1997

Risk factors for left ventricular hypertrophy in chronic hemodialysis patients.

Left ventricular hypertrophy is reported to be common in chronic hemodialysis patients, and also to increase the risk for mortality in chronic hemodialysis patients. An echocardiographical and clinical study was carried out to investigate the risk factors for left ventricular hypertrophy in 151 non-diabetic chronic hemodialysis patients without valvular diseases or myocardial infarction in two hemodialysis units in Fukuoka, Japan. The left ventricular mass index (LVMI) correlated positively to age, systolic blood pressure and interdialysis weight gain while it correlated negatively to the duration of hemodialysis therapy and hematocrit. Resorting to a multivariate analysis, the LVMI was found to positively correlate to age and the systolic blood pressure while it correlated negatively with the duration of hemodialysis therapy and the hematocrit level. These findings suggest that hypertension and anemia may thus be independent risk factors for left ventricular hypertrophy.

Cross-Sectional Studies↗