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Biomedical subjects

Y Okuda

Publications and source records attributed to Y Okuda.

At least 19 recordsLinked to original sources
PubMed2000

Intrathecal administration of neutralizing antibody against Fas ligand suppresses the progression of experimental autoimmune encephalomyelitis.

A therapy aimed at blocking the Fas/Fas ligand (FasL) system was investigated using a relapsing form of experimental autoimmune encephalomyelitis (EAE) in mice, an animal model of multiple sclerosis (MS). Intracisternal administration of neutralizing antibody against FasL during the progression phase of EAE significantly reduced the severity of the disease with milder inflammation and myelin breakdown in the central nervous system (CNS). These results raised the possibility that the Fas/FasL system might contribute to tissue destruction in the CNS in the acute phase of EAE and that the intrathecal administration of neutralizing antibody against FasL may be beneficial for suppression of the acute phase of MS.

Acute Disease↗
PubMed2000

Enhancement of Th2 response in IL-6-deficient mice immunized with myelin oligodendrocyte glycoprotein.

To investigate the mechanism for the resistance of IL-6-deficient mice to experimental autoimmune encephalomyelitis (EAE), we examined the production of cytokines in lymph nodes (LNs) of wild-type and IL-6-deficient mice immunized with myelin oligodendrocyte glycoprotein (MOG) by reverse transcriptase-polymerase chain reaction analysis. Significant up-regulation of IL-4 production and down-regulation of IFN-gamma production were found in LNs from IL-6-deficient mice as compared to LNs from wild-type mice. Administration of IL-6, which caused typical EAE in IL-6-deficient mice immunized with MOG, reduced IL-4 production but did not restore IFN-gamma production in LNs of IL-6-deficient mice. These results implied that the resistance of IL-6-deficient mice to EAE might be mainly due to enhancement of Th2 response.

Animals↗
PubMed2000

Nitric oxide production of rat Leydig and Sertoli cells is stimulated by round spermatid factor(s).

In this study, we provide evidence of cell-to-cell interaction between rat germ cells and Leydig or Sertoli cells in relation to nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) messenger RNA (mRNA) expression. As a result of being cultured in a round spermatid-conditioned medium (RSd-CM), NO production in both Leydig and Sertoli cells increased in proportion to the length of the culture period. iNOS mRNA expression in both types of cells also increased in a dose-dependent manner as a result of being cultured with RSd-CM. This increase was detected as early as 3 h and was maintained up to 24 h. In contrast, neither NO production nor iNOS mRNA increased in either type of cell following culture in a pachytene spermatocyte-conditioned medium (PS-CM). Our findings suggest that RSd may control NO production of Leydig and Sertoli cells. This cell-to-cell interaction may be an important mechanism of regulation of testicular function.

Animals↗
PubMed2000

Effect of hypoxia on nitric oxide production and its synthase gene expression in rat smooth muscle cells.

It has not been clarified yet as to whether hypoxia and inflammation affect NO synthesis. In this study, we investigated the transcription of inducible nitric oxide synthase (iNOS) mRNA and the production of nitric oxide (NO) in rat smooth muscle cells (SMCs) cultured under hypoxic conditions in the presence and absence of proinflammatory cytokine interferon-gamma (IFN-gamma) and lipopolysaccharide (LPS). We found that hypoxia inhibited the production of NO but did not affect the transcription of iNOS mRNA in rat SMCs treated with IFN-gamma, LPS, or both. These results indicate that O(2) is involved in the regulation of NO synthesis in inflammatory tissues.

Animals↗
PubMed2000

The effect of apoptosis inhibitors on experimental autoimmune encephalomyelitis: apoptosis as a regulatory factor.

The effect of apoptosis inhibitors on experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis, was investigated by intraperitoneal or intracisternal administration of apoptosis inhibitors Ac-YVAD-cmk and zVAD-fmk. After onset of the disease, these agents had no suppressive effect on EAE and resulted in impaired recovery or earlier relapse. Histological examination revealed that administration of zVAD-fmk suppressed the apoptotic death of inflammatory cells in the central nervous system (CNS) of mice with EAE. The results indicated that the apoptotic elimination of infiltrated cells in the CNS might be one of the recovery mechanisms in EAE.

Amino Acid Chloromethyl Ketones↗
PubMed2000

Structure-activity relationship in potentially anti-tumor promoting benzalacetone derivatives, as assayed by the epstein-barr virus early antigen activation.

The in vitro anti-tumor promoting activities of antimutagenic benzalacetone (4-phenyl-3-buten-2-one), its monosubstituted derivatives and related compounds, cinnamaldehydes and cinnamic acids, were evaluated by determining the inhibitory effect on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells. In this short-term assay, benzalacetone, which is the basic structure of dehydrozingerone (one-half analog of curcumin) inhibited the EBV-EA activation; the IC(50) value, the molar ratio of benzalacetone to TPA needed for inhibiting 50% of positive cells activated with 32 pmol TPA, was 129. IC(50) values of 2- and 4-methoxybenzalacetones were about one-half of that of benzalacetone and the methoxy compounds were more effective than hydroxybenzalacetones. IC(50) values of chloro- and trifluoromethyl-benzalacetones were higher than that of benzalacetone, indicating that these compounds are weaker inhibitors. In addition, the position of a substituent on the benzene ring affected the inhibitory effect. In benzalacetone derivatives substituted by a hydroxy-, methoxy-, chloro- or trifluoromethyl group, the 2-substituted derivatives exhibited the strongest inhibitory effect, followed by the 3- and the 4-substituents. Cinnamic acid derivatives also decreased the inhibitory effects in the same order. In the side chain of benzalacetone, the terminal group adjacent to the carbon-carbon double bond also affected the inhibitory effect. The conversions of the methylketone to aldehyde and carboxyl groups, i.e., cinnamaldehyde and cinnamic acid, increased the inhibitory effect: the IC(50) values were about one-third of that of benzalacetone. beta-Methyl styrene, which in the side chain has no carbonyl group adjacent to the double bond, inhibited the EBV-EA activation at the concentration of about one-third of that of benzalacetone, indicating that the carbonyl group negatively affects the inhibitory effect. This agreed with the previous observation between isoeugenol and dehydrozingerone, 4-hydroxy-3-methoxy derivatives of beta-methyl styrene and benzalacetone, respectively. The mechanism of the EBV-EA activation inhibition was discussed by being compared with the inhibition of mutagenesis for which the unsaturated bonded-carbonyl system is necessary.

Acrolein↗
PubMed2000

Enhanced graft healing of high-porosity expanded polytetrafluoroethylene grafts by covalent bonding of fibronectin.

The effect of covalent bonding of fibronectin on the patency and graft healing of high-porosity expanded polytetrafluoroethylene (ePTFE) grafts was evaluated. Bilateral carotid grafting was performed in ten mongrel dogs using high-porosity (60 microm) ePTFE grafts, 4 cm in length and 4 mm in internal diameter, that either had been pretreated by the covalent bonding of fibronectin (fibronectin grafts) or were untreated (control grafts). The grafts were harvested 4 to 6 weeks after surgery and subjected to macroscopic and light-microscopic observations. There was no significant difference in patency between the fibronectin grafts and the control grafts with rates of 80% and 70%, respectively. The thrombus-free area score was significantly greater in the fibronectin grafts than in the control grafts, at 86.9% vs 34.0%. Furthermore, the pseudointima was better replaced by fibrous tissue in the fibronectin grafts than in the control grafts, being lined with a layer of endothelial-like cells. More transmural tissue ingrowth was evident in the fibronectin grafts than in the control grafts. The covalent bonding of fibronectin improves graft healing by stimulating transmural tissue ingrowth in high-porosity ePTFE grafts.

Animals↗
PubMed2000

High-porosity expanded polytetrafluoroethylene grafts for thoracic vena cava replacement with or without an omentum wrap.

We previously reported that, in a short-term thoracic inferior vena cava (IVC) replacement, a high-porosity expanded polytetrafluoroethylene (ePTFE) graft (fibril length 60 microm) performed well without altering the short-term patency, and that the healing of the high-porosity ePTFE graft was accelerated by an omentum wrap. The purpose of this study was to examine the long-term performance of the high-porosity ePTFE graft with or without an omentum wrap. Eighteen grafts were placed as a thoracic IVC replacement in dogs. Nine of the grafts were wrapped in an omental pedicle flap while the other 9 were not. At 1 month and 6 months, the grafts were harvested and examined for a pathological analysis. During the observation period, one dog died of a viral infection, while the other 17 dogs survived. At 1 month and 6 months, the patency rates of the 17 grafts were 100% regardless of the presence or absence of an omentum wrap. The healing of the grafts without omentum wrap was incomplete 6 months after implantation; granulation tissue was present in the center of the pseudointima. The grafts healed completely by the addition of an omentum wrap. Our data suggest that, with an omentum wrap, the high-porosity ePTFE graft is fully expected to show a good long-term function.

Animals↗
PubMed2000

Delapril versus manidipine in hypertensive therapy to halt the type-2-diabetes-mellitus-associated nephropathy.

Thirty-nine hypertensive patients with type 2 diabetes mellitus were followed under long-term treatment (mean, 20.7 months) with manidipine hydrochloride, a Ca antagonist, or delapril hydrochloride, an ACE inhibitor, at nine institutions. Both the treatments showed similar antihypertensive effects, although slight but significantly larger decreases were observed in systolic and mean blood pressures at months 12 and 24 in the patients treated with manidipine (P < 0.02). The urinary albumin excretion index (AEI) tended to increase throughout the study in both treatment groups, but no significant difference in AEI was observed between the two treatment groups at any time point. Overt albuminuria developed in four patients on manidipine but did not appear in any of the patients on delapril. The risk of progression to overt albuminuria was significantly different between manidipine and delapril groups (P = 0.011). No increase in serum creatinine (Cr) was observed with delapril. The average excretion indexes of tubular markers such as beta2-microglobulin, alpha1-microglobulin, and NAG tended to be higher in the patients on manidipine than in those on delapril. Taken in sum, these findings suggest that the ACE inhibitor delapril is more beneficial than the Ca antagonist manidipine in the treatment of diabetic renal diseases via mechanisms other than the blood pressure regulation, partly through their different effects on tubular function. In conclusion, delapril was significantly more effective than manidipine in inhibiting progression to overt albuminuria in hypertensive type 2 diabetes mellitus patients.

Adult↗
PubMed2000

Bile acids increase intracellular Ca(2+) concentration and nitric oxide production in vascular endothelial cells.

The effects of bile acids on intracellular Ca(2+) concentration [Ca(2+)](i) and nitric oxide production were investigated in vascular endothelial cells. Whole-cell patch clamp techniques and fluorescence measurements of [Ca(2+)](i) were applied in vascular endothelial cells obtained from human umbilical and calf aortic endothelial cells. Nitric oxide released was determined by measuring the concentration of NO(2)(-). Deoxycholic acid, chenodeoxycholic acid and the taurine conjugates increased [Ca(2+)](i) concentration-dependently, while cholic acid showed no significant effect. These effects resulted from the first mobilization of Ca(2+) from an inositol 1,4,5-triphosphate (IP(3))-sensitive store, which was released by ATP, then followed by Ca(2+) influx. Both bile acids and ATP induced the activation of Ca(2+)-dependent K(+) current. Oscillations of [Ca(2+)](i) were occasionally monitored with the Ca(2+)-dependent K(+) current in voltage-clamped cells and Ca(2+) measurements of single cells. The intracellular perfusion of heparin completely abolished the ATP effect, but failed to inhibit the bile acid effect. Deoxycholic acid and chenodeoxycholic acid enhanced NO(2)(-) production concentration-dependently, while cholic acid did not enhance it. The bile acids-induced nitric oxide production was suppressed by N(G)-nitro-L-arginine methyl ester, exclusion of extracellular Ca(2+) or N-(6-aminohexyl)-5-chloro-l-naphthalenesulphonamide hydrochloride (W-7) and calmidazolium, calmodulin inhibitors. These results provide novel evidence showing that bile acids increase [Ca(2+)](i) and subsequently nitric oxide production in vascular endothelial cells. The nitric oxide production induced by bile acids may be involved in the pathogenesis of circulatory abnormalities in liver diseases including cirrhosis.

Animals↗
PubMed2000

Cremasteric reflex test as an objective indicator of spinal anaesthesia.

We studied 100 men who were scheduled for urological surgery (Group 1) and another 50 men for orthopaedic surgery (Group 2). We attempted to anaesthetise both sides of the lower body in Group 1 and to anaesthetise one leg in Group 2 by injecting 0.3% hyperbaric dibucaine intrathecally. The presence or absence of the cremasteric reflex and loss of sensation to pinprick higher than the first lumbar dermatome were examined by two researchers who were blind to each other's results. In Group 1, both the reflex and the pinprick sensation were always absent bilaterally 5 min after intrathecal injection. In Group 2, in 23 of 50 patients the reflex had become absent bilaterally; in all these patients, bilateral sensory loss was detected. In the remaining 27 patients, both the reflex and the pinprick sensation were absent on the operation side, whereas both were present on the nonoperation side. Sensitivity, specificity and positive or negative predictive value for the cremasteric reflex were all 100%. Disappearance of the cremasteric reflex is a simple objective indicator of spinal anaesthesia at the first lumbar dermatome. This test may be useful in patients who cannot give reliable answers to conventional tests, such as the pinprick test.

Adult↗
PubMed2000

Inhibition of apoptosis in cultured immature rat Leydig cells by human chorionic gonadotropin associated with Bcl-2 mRNA expression.

Bcl-2 is the first identified negative regulator of apoptotic cell death. When the level of Bcl-2 mRNA in rat whole testes was examined in the present study, it gradually decreased in rats from 2.5 to 9 weeks old. We also examined the effect of human chorionic gonadotropin (hCG) on apoptosis and the level of Bcl-2 mRNA expression in immature Leydig cells in vitro. When the cells were cultured with serum free media (SFM), Bcl-2 mRNA levels gradually decreased. On the other hand, the level of Bcl-2 mRNA in cells treated with 50 ng/ml of hCG decreased at 6 h, but increased after 12 h. At 24 h, the level of Bcl-2 mRNA in the treated cells was almost the same as that of control cells (time = 0). At 12 h after the addition of various concentrations (from 0.1-1000 ng/ml) of hCG, Bcl-2 mRNA levels increased in a dose-dependent manner. An analysis of DNA fragmentation showed that treatment with hCG prevents the apoptosis of immature Leydig cells. Our findings suggest that Bcl-2 mRNA may be related to the programmed cell death of immature rat Leydig cells in vitro, which are inhibited by hCG.

Animals↗
PubMed2000

Creation of aortic dissection model in swine.

The use of mongrel dogs for experimental purposes was recently restricted and this report presents the experience of creating an aortic dissection model in swine. All the swine in group 1 were anesthetized without pentobarbital and the descending aorta was side-clamped during the creation of the aortic dissection. The false lumen of the completed dissection was patent in the long term despite not having the anchoring suture that the previous canine model required to stabilize the opening of the entry tear. All the swine anesthetized with pentobarbital (ie, group 2) died of heart failure either during cross-clamping of the descending aorta or postoperative aortography. In conclusion, creation of a thoracic aortic dissection is possible in swine, but cross-clamping of the thoracic descending aorta and pentobarbital anesthesia should be avoided.

Aortic Dissection↗
PubMed2000

[Anesthetic management of a patient with West syndrome].

A 21-year-old female with West syndrome was scheduled for resection of hordeolum. She had an episode of convulsion at three months of age, and was diagnosed as having West syndrome at one year of age. She had epileptic seizures twice a week in spite of administration of phenytoin, clonazepam and sodium valproate. These drugs had been administered till the morning of the surgery. After premedication with atropine 0.25 mg, anesthesia was induced with propofol (12-->10-->8 mg.kg-1.h-1). The tracheal intubation was performed with vecuronium 0.1 mg.kg-1 and anesthesia was maintained with continuous infusion of propofol 6-8 mg.kg-1.h-1 and local infiltration with 1.0% lidocaine 5 ml. We administered phenytoin to prevent epileptic seizures during the surgery. No epileptic seizures occurred perioperatively. We conclude that propofol may be useful for a patient with West syndrome, and we should be careful not to lower the threshold for convulsion during the perioperative period.

Adult↗
PubMed2000

[Anesthetic management of bilateral lung lavage for pulmonary alveolar proteinosis--comparison between sevoflurane and propofol].

A 55-year-old man with pulmonary alveolar proteinosis underwent lung lavage under general anesthesia using sevoflurane three years ago. Although transient hypoxia occurred postoperatively, there were no complications. Because of the recent deterioration of his symptoms, he was rescheduled for lung lavage. Anesthesia was induced with propofol 120 mg and fetanyl 0.2 mg. Vecuronium 7 mg was administered to facilitate tracheal intubation using a double-lumen tube. Anesthesia was maintained with propofol 4 mg.kg-1.h-1. Electrocardiogram, blood pressure, SPO2, EtCO2 and rectal temperature were monitored intraoperatively. We also checked PaO2 when necessary. Although transient hypoxia occurred after the procedure, it receded spontaneously. Since inhalation anesthetics inhibit hypoxic pulmonary vasoconstriction, intravenous anesthetics may be more useful for patients with severe pulmonary alveolar proteinosis.

Anesthesia, General↗
PubMed2000

[Anesthetic management of an emergency surgery for panperitonitis during an asthmatic attack].

We report anesthetic management of an emergency surgery for panperitonitis during an asthmatic attack in a patient with angina pectoris. A 71-year-old male patient, complaining of abdominal pain and dyspnea, was diagnosed as having panperitonitis and asthmatic attack by surgeons in the emergency room. General anesthesia was induced by intravenous injection of propofol (30 mg), ketamine (30 mg), fentanyl (200 micrograms), suxamethonium (60 mg) and diltiazem (5 mg) following cannulation of the left radial artery for continuous monitoring of direct arterial pressure. Anesthesia was maintained by continuous infusion of propofol (4-10 mg.kg-1.h-1) and ketamine (1 mg.kg-1.h-1) in combination with intermittent epidural injection of local anesthetics. Although sudden onset of increased peak airway pressure occurred 45 minutes after starting operation, 50 mg of propofol injection and 500 mg of aminophyline infusion could relieve this high airway pressure. Because increased peak airway pressure appeared frequently and this could not be relieved by bolus injection of propofol, we changed the intravenous anesthesia to nitrous oxide-oxygen-isoflurane (GOI). After this change, no asthmatic attack occurred during the operation. While the mechanical ventilation was required during the early postoperative period along with infusion of aminophyline and inhalation of beta-stimulants, the patient was weaned successfully from the mechanical ventilation 12 hours postoperatively. It was speculated that the intraoperative asthmatic attack might have been caused by light level of anesthesia with propofol and ketamine. We concluded that other analgesics, such as fentanyl or epidural local anesthetics, must have been supplemented at proper timing during the continuous infusion of propofol and ketamine during the surgery.

Aged↗
PubMed2000

[Usefulness of laryngeal mask for difficult intubation in a child with congenital laryngeal webs].

We report a case of difficult intubation with congenital laryngeal web. An 11-year-old boy was scheduled for urinary surgery. After anesthetic induction, the anesthesiologist encountered resistance at the vocal cord preventing satisfactory intubation. A size 3 laryngeal mask was immediately inserted, and an adequate airway was obtained. We found a laryngeal web at the vocal cord by bronchoscope inserted thorough the laryngeal mask. The peroperative course was uneventful. Immediately after removal of the laryngeal mask, the patient developed airway obstruction due to sputum and/or laryngeal spasm. The obstruction was relieved through application of positive pressure ventilation and aspiration of the sputum.

Airway Obstruction↗