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Biomedical subjects

N Ueda

Publications and source records attributed to N Ueda.

At least 217 records · Page 12Linked to original sources

Effects of zopiclone, triazolam, and nitrazepam on standing steadiness.

We examined the effects of the nonbenzodiazepine hypnotic zopiclone and the benzodiazepine hypnotics triazolam and nitrazepam on standing steadiness. Eight healthy volunteers received placebo, zopiclone (7.5 mg), triazolam (0.25 mg), and nitrazepam (5 mg) in a random-order, double-blind crossover design. Postural sway was assessed before and 1 and 2 h after drug administration using a stabilometer connected to a microcomputer. Triazolam significantly impaired standing steadiness. Zopiclone also impaired standing steadiness but the degree of impairment seemed to be less marked. Nitrazepam 5 mg had no significant effects on postural sway. Triazolam 0.25 mg, zopiclone 7.5 mg, and nitrazepam 5 mg, which are reported to be equipotent to each other as hypnotics, are not equipotent with respect to their effects on postural sway.

Adult↗

Mitogen-activated protein kinase and its activator are regulated by hypertonic stress in Madin-Darby canine kidney cells.

Madin-Darby canine kidney cells behave like the renal medulla and accumulate small organic solutes (osmolytes) in a hypertonic environment. The accumulation of osmolytes is primarily dependent on changes in gene expression of enzymes that synthesize osmolytes (sorbitol) or transporters that uptake them (myo-inositol, betaine, and taurine). The mechanism by which hypertonicity increases the transcription of these genes, however, remains unclear. Recently, it has been reported that yeast mitogen-activated protein (MAP) kinase and its activator, MAP kinase-kinase, are involved in osmosensing signal transduction and that mutants in these kinases fail to accumulate glycerol, a yeast osmolyte. No information is available in mammals regarding the role of MAP kinase in the cellular response to hypertonicity. We have examined whether MAP kinase and MAP kinase-kinase are regulated by extracellular osmolarity in Madin-Darby canine kidney cells. Both kinases were activated by hypertonic stress in a time- and osmolarity-dependent manner and reached their maximal activity within 10 min. Additionally, it was suggested that MAP kinase was activated in a protein kinase C-dependent manner. These results indicate that MAP kinase and MAP kinase-kinase(s) are regulated by extracellular osmolarity.

Animals↗

In vivo osmoregulation of Na/myo-inositol cotransporter mRNA in rat kidney medulla.

myo-Inositol, a major compatible osmolyte in renal medulla, is accumulated in kidney-derived epithelial cells cultured in hypertonic media via Na/myoinositol cotransporter (SMIT). The altered medium osmolality of Madin-Darby canine kidney cells leads to changes in the transcription of the SMIT gene and mRNA abundance. To investigate whether SMIT is regulated by tonicity in vivo, renal medullary myoinositol and SMIT mRNA was measured in rats in hydrated and dehydrated states. Rats were divided into two groups: (1) hydrated rats, free access to 3% sucrose water; (2) dehydrated rats, 3 days of water deprivation. Urine sodium, potassium, urea, and osmolality in dehydrated rats were significantly higher than in hydrated rats. Renal medullary sodium, urea, and myo-inositol in dehydrated rats were significantly higher than in hydrated rats. Northern analysis revealed that there was a message hybridized to SMIT cDNA in the cortex and outer and inner medulla of the kidney. Compared with hydrated rats, SMIT mRNA in dehydrated rats was 2.6-fold higher in the outer medulla and 2.5-fold higher in the inner medulla. These results indicate that there is osmoregulatory SMIT in the outer and inner medulla of the kidney and that myo-inositol accumulation in this region is probably due to the increased expression of the SMIT gene.

Animals↗

[Respiratory disease in the tertiary emergency hospital].

We studied treatment for respiratory emergencies over the past 11 years at our hospital, a tertiary emergency center. We supply intermediate management services to a general hospital. A total of 13,667 patients received tertiary emergency medical care (annual mean: 1243). Of these, 1592 had severe respiratory disturbances (11.5% of the total; 971 males, 621 females; annual mean: 143). The most frequently seen conditions were COPD, respiratory failure due to old pulmonary tuberculosis) 35.2%, mortality failure due to old pulmonary tuberculosis (35.2%, mortality rate: 29.7%), bronchial asthma (26.0%, mortality rate 9.6%), pneumonia (19.0%, mortality rate 20.4%), and pneumothorax (10.3%). Very few of the patients with bronchial asthma who arrived in cardiopulmonary arrest survived. Patients with interstitial pneumonia, paraquat lung, pulmonary obstruction, adult respiratory distress syndrome, and near-drowning all had poor prognoses, as did victims of attempted suicide by hanging and attempted murder by strangulation. About 25% of the patients required mechanical ventilation, and about half of those patients died. Changes in prehospital care and in care given after critical care is no longer needed are important in improving the prognoses for patients with respiratory emergencies.

Adult↗

Double burst stimulation with submaximal current.

The present study evaluated responses to double burst stimulation (DBS) at supramaximal and submaximal currents in 30 adult patients. Usually, DBS is applied with supramaximal stimulation, but this may be quite uncomfortable for the awake patient. Therefore, the authors investigated whether it is possible to obtain an accurate assessment of significant residual neuromuscular blockade if the stimulus current is reduced to 30 mA. In all patients, neuromuscular response to DBS three three (DBS3.3), DBS three two (DBS3.2) and train-of-four (TOF) stimulation at supramaximal and/or submaximal currents was recorded using a mechanomyograph, and the ratios of the fourth to the first twitch (T4/T1) induced by TOF stimulation at supramaximal current, and the height of the second response to the first (D2/D1) induced by DBS at 30 mA and supramaximal current were calculated. The relations between control T4/T1 ratios determined by supramaximal TOF stimulation and D2/D1 ratios determined by supramaximal DBS3.3 and submaximal DBS3.3 were Y = 0.99X + 0.08 and Y = 1.01X + 0.04, respectively, and there was no statistical difference between the two regression lines. The same relation between T4/T1 ratios and D2/D1 ratios by DBS3.2 were Y = 0.69X + 0.05 and Y = 0.72X + 0.02, respectively, and there was no significant difference. It is concluded that evaluation of the response to DBS at 30 mA has the same reliability as evaluation with supramaximal current.

Adult↗

Apoptosis.

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Animals↗

[The mechanism of potentiation of the antitumor effect of 5-fluorouracil by methionine-free intravenous amino acid solution (AO-90) in rats].

AO-90, a methionine-free intravenous amino acid solution (7.43%) showed to potentiate the antitumor effect of 5-fluorouracil (5-FU) when concomitantly used as the nitrogen source in total parenteral nutrition (TPN) in Yoshida sarcoma (YS)-bearing rats. In the present experiment, this potentiation mechanism was studied by determining the serum methionine level and tumor methylenetetrahydrofolate (CH2FH4) content in YS-bearing Donryu rats given AO-90 (nitrogen 0.73g/kg on the 1st day and 1.46g/kg for the remaining 6 days) by TPN for 1 week. The rats were subcutaneously inoculated with 10(4) YS cells in the dorsum 3 days before the start of TPN. Inhibition of thymidylate synthase activity in tumor tissue after dosing of AO-90 (nitrogen 0.68g/kg on the 1st day and 1.36 g/kg for the remaining 6 days) by TPN along with daily intraperitoneal dosing of 5-FU (10 mg/kg) was also evaluated with the inoculation of 10(6) tumor cells. The results were compared with those in tumor-bearing rats given TPN with a commercially available amino acid solution containing methionine. On day 5 of TPN, the tumor-bearing rats given AO-90 showed a significantly lower serum methionine level than the control rats: 101 +/- 11 mumol/l versus 29 +/- 14 mumol/l (p < 0.01); and a higher CH2FH4 content in tumor: 7.0 +/- 2.8 pmol/g protein versus 23.7 +/- 16.6 pmol/g protein (p < 0.05). Thymidylate synthase inhibition was 81.2 +/- 5.1% in the AO-90 group and 30.9 +/- 26.3% in the control group (p < 0.01). The results of the present study suggest that AO-90 potentiate the antitumor effect of 5-FU by biochemical modulation. AO-90 concomitantly given with 5-FU for 7 days was effective not only in the allogeneic tumor model, but also in WKAH and SHR rats previously inoculated with 10(6) of syngeneic KDH-8 hepatoma cells and SST-2 adenocarcinoma cells, respectively. Weight of SST-2 adenocarcinoma in SHR rats after the TPN period was significantly smaller in the AO-90 group than in the control rats given methionine-containing TPN and 5-FU: 2.66 +/- 0.91 versus 5.12 +/- 2.11 (p < 0.05).

Amino Acids↗

[A new neuromuscular transmission monitor (TOF Guard): the rationale behind the method and its clinical usefulness].

TOF Guard is one of the latest developments in the field of neuromuscular monitoring equipment. This system uses a miniature acceleration transducer (a piezo-electric ceramic wafer is used), simply fastened to the thumb with tape. The rationale behind the method is Newton's second law, stating that the acceleration is directly proportional to the force. In this study, authors assessed the accuracy of this system in clinical use, comparing with the force transducer method (Myograph 2000). The result showed that there was a very close positive correlation between the values of T1, TOF ratio and posttetanic count simultaneously measured by both methods. The coefficient of correlation was 0.96, and its significance level was P < 0.001. From the clinical view point, it is concluded that TOF Guard is very useful because of its accuracy and because the equipment is easy to handle, compact and of low price as a neuromuscular monitoring system for routine anesthesia.

Adult↗

Activin A induces apoptotic cell death.

Activins, members of a family of the transforming growth factor beta (TGF beta), are involved in the regulation of multiple biological events. We found a novel effect of activin A on hybridoma and myeloma cell lines. Activin A exhibited a cytotoxic effect on interleukin-6 (IL-6)-dependent B9 cells and induced a significant increase in the proportion of fragmented DNA. B9 cells exposed to activin A released high amounts of lactate dehydrogenase (LDH) and exhibited the typical ladder pattern of DNA fragmentation of apoptotic cells. IL-6 did not prevent apoptosis of B9 cells induced by activin A. The cytotoxicity of activin A to B9 cells was suppressed by follistatin. On the other hand, TGF beta showed no cytotoxic effect on B9 cells. These findings indicate that apoptosis induced by activin A could be one of the mechanisms to prevent uncontrolled cell growth.

Activins↗

Arachidonate 12-lipoxygenase of platelet-type in human epidermal cells.

A homogenate of epidermal cells isolated from human skin converted arachidonic acid to 12S-hydroxy-5, 8,10,14-eicosatetraenoic acid and 15-hydroxy-5, 8,11,13-eicosatetraenoic acid as the main lipoxygenase products. The production of these hydroxy acids was not stimulated by the addition of 1 mM NADPH required for cytochrome P-450 reaction, but inhibited by 65-75% with 40 microM nordihydroguaiaretic acid, a nonspecific lipoxygenase inhibitor. In addition to these lipoxygenase products, the epidermal cell homogenate converted arachidonic acid to prostaglandin E2 together with minor amounts of prostaglandins D2 and F2a and 12-hydroxy-5,8,10-heptadecatrienoic acid. Thromboxane B2 was not detected. This finding rules out the possible contamination of platelet 12-lipoxygenase in the epidermal cells. After subcellular fractionation of the epidermal cell homogenate, the 12-lipoxygenase activity was found in the 164,000 x g supernatant, the 164,000 x g pellet, and the 10,000 x g pellet. The cytosolic enzyme and the enzymes solubilized from the two pellets produced 12S-hydroperoxy-5,8,10,14-eicosatetraenoic acid as the primary product in contrast to cytochrome P-450 which produces primarily hydroxy acids. The 12-lipoxygenase in the 164,000 x g supernatant and the solubilized enzymes from the 164,000 x g pellet and 10,000 x g pellet were precipitable by antibodies raised against human platelet 12-lipoxygenase, but not by antibodies against porcine leukocyte 12-lipoxygenase. The immunoprecipitated 12-lipoxygenase from each fraction was almost inactive with linoleic acid as substrate, characteristic of 12-lipoxygenase of platelet-type. Furthermore, 12-lipoxygenase mRNA in the epidermal cells could be reverse-transcribed and amplified by polymerase chain reaction with the primers specific for human platelet 12-lipoxygenase cDNA, but not with those for porcine leukocyte 12-lipoxygenase cDNA. Thus, the 12-lipoxygenase of human epidermal cells is similar to human platelet 12-lipoxygenase in terms of immunogenicity, catalytic property, and primary structure, and distinct from leukocyte 12-lipoxygenase.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗

Increase in bleomycin-detectable iron in ischaemia/reperfusion injury to rat kidneys.

Iron has been shown to be important in ischaemic, immune and toxic forms of tissue injury in various organs. Although it is generally accepted that iron participates in the generation of powerful oxidant species (e.g. hydroxyl radicals) there has not been any direct evidence that iron capable of catalysing free-radical reactions is increased in tissues in these models of injury. In the present study we demonstrate that ischaemia/reperfusion injury to the kidney results in no significant change in total, nonhaem or ferritin iron levels, but there is a marked and specific increase in bleomycin-detectable iron (capable of catalysing free-radical reactions) in the kidney. The increase in bleomycin-detectable iron is observed only after reperfusion but not during the ischaemic period. In a separate study we demonstrate that despite a drastic reduction in the iron content in the kidney, as a result of feeding an iron-deficient diet, there is a similar and a marked increase in the bleomycin-detectable iron in kidneys accompanied by a lack of protection against ischaemia/reperfusion injury.

Acute Kidney Injury↗

Immunocytochemical localization of prostaglandin endoperoxide synthase in the bovine intestine.

The localization of prostaglandin (PG) endoperoxide synthase in bovine intestine was examined immunocytochemically with polyclonal antibody raised against PG endoperoxide synthase purified from bovine seminal glands. The most intense positive staining reaction for the enzyme was present in mast cells. Mast cells were found to be widely distributed in the intestinal wall, and were particularly numerous in the lamina propria. Most of the mast cells in the lamina propria of the intestinal villi were elongated and oriented with their long axis parallel to the plane of the absorptive epithelium. In whole mount preparations of jejunal villi, mast cells were seen to form a two-dimensional network in the lamina propria. In addition to mast cells, smooth muscle cells of the inner circular muscle layer and muscularis mucosae, nerve cells and fibers, endothelial cells of arterioles, and serosal epithelial cells also showed faint to moderate staining for the enzyme. These results suggested that mast cells are the major source of PGs in the bovine intestinal wall. The characteristic arrangement of mast cells in the intestinal villi may be related to their functions in this portion of the bovine intestine.

Animals↗

Bronchial atresia: report of a case and review of the literature.

We report herein an unusual presentation of bronchial atresia in a 28-year-old woman, in whom hyperlucency of the ventral segment, distal to a right extrahilar mass found on a routine chest X-ray, was not recognized. Atresia of the medial branch of the ventral segmental bronchus (B3b) with mucoid impaction in the dilated bronchus was finally disclosed by a right upper lobectomy. The patient had been asymptomatic, and physical examination demonstrated no abnormal findings such as decreased breathing sounds over the affected lung. Localized hyperlucency and a mass are the characteristic radiographic features of bronchial atresia. In the present case, however, hyperlucency distal to the mass, which was retrospectively evident on a computed tomogram of the chest, was not recognized. The preoperative diagnosis was also made difficult by the fact that the atresia was located on a subsequential branch (B3b) of the ventral segmental bronchus of the right upper lobe. Since computed tomography and magnetic resonance imaging are able to make an accurate diagnosis of bronchial atresia possible, surgery is often not indicated for asymptomatic patients. Moreover, although surgical intervention is required for patients with complications such as encroachment of normal pulmonary tissue or infection, resection should be as limited as possible to preserve normal lung tissue.

Adult↗

Evidence suggesting that iron and calcium are interrelated in oxidant-induced DNA damage.

The effect of iron chelators and agents that buffer cytosolic-free calcium ([Ca2+]i) on hydrogen peroxide-induced DNA strand breaks in LLC-PK1 cells has not been previously examined. In addition, the interrelationship between iron and calcium in the pathogenesis of DNA damage has not been studied in any model of tissue injury. Exposure of LLC-PK1 cells to 1 mM hydrogen peroxide resulted in marked DNA damage, as measured by the alkaline unwinding assay (residual intact double stranded DNA at 10 min, control: 88 +/- 1%; hydrogen peroxide-treated cells: 17 +/- 3%, N = 8). The iron chelators, 1,10-phenanthroline and deferoxamine, and agents which buffer [Ca2+]i, BAPTA and quin-2, provided highly significant protection against hydrogen peroxide-induced DNA strand breaks. We then examined the effect of iron chelators on hydrogen peroxide-induced rise in [Ca2+]i in LLC-PK1 cells. Both 1,10-phenanthroline and deferoxamine prevented the marked and sustained rise in [Ca2+]i induced by exposure of LLC-PK1 cells to 1 mM hydrogen peroxide ([Ca2+]i at 15 min, control 100 +/- 3 nM; hydrogen peroxide 195 +/- 14 nM; 1,10-phenanthroline + hydrogen peroxide 100 +/- 4 nM; deferoxamine + hydrogen peroxide 106 +/- 4 nM; N = 4). We excluded the possibility that the iron chelators were directly chelating calcium by performing experiments using a cell free system. We also confirmed that BAPTA and quin-2, in concentrations used in our study, chelate calcium but not iron or copper.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcium↗

Gentamicin-induced mobilization of iron from renal cortical mitochondria.

Iron, presumably by participating in generation of hydroxyl radical or other oxidant species or initiation of lipid peroxidation, has been shown to play an important role in several models of tissue injury, including acute renal failure induced by the antibiotic gentamicin. However, the sources of iron remain unknown. Rat renal mitochondria incubated at 37 degrees C with gentamicin resulted in a time- (15-60 min) and a dose-dependent (0.01-5 mM) iron release as measured by formation of iron-bathophenanthroline sulfonate complex FeII-(BPS)3 [at 60 min, control: 1.2 +/- 0.1 nmol/mg protein, n = 7; gentamicin (5 mM): 5.1 +/- 0.4 nmol/mg protein, n = 7]. No formation of FeII(BPS)3 complex was detected in the absence of mitochondria or when incubations were carried out at 0 degrees C. Similar results were obtained when 2,2'-dipyridyl, another iron chelator, was used for measurement of iron release. On the basis on our previous study that gentamicin enhances generation of hydrogen peroxide by renal cortical mitochondria, we examined whether effect of gentamicin on iron release is mediated by hydrogen peroxide. Catalase (which decomposes hydrogen peroxide), but not heat-inactivated catalase, as well as pyruvate, a potent scavenger of hydrogen peroxide, prevented gentamicin-induced iron mobilization. Superoxide dismutase, a scavenger of superoxide anion, or hydroxyl radical scavengers (dimethylthiourea or sodium benzoate) had no effect. Taken together, the data with scavengers indicate that gentamicin-induced iron mobilization from mitochondria is mediated by hydrogen peroxide.

2,2'-Dipyridyl↗

A solitary renal mass as the only manifest lesion of a B-cell lymphoma.

A patient with a solitary renal mass as the only manifest lesion of B-cell lymphoma was reported. The surgical specimen revealed that the lesion was histologically limited to the renal parenchyma. Liver dysfunction prevented him from receiving systemic chemotherapy. Mediastinal and mesenteric lymph node involvements developed 6 months later. Fortunately, the patient survived without recurrence for 18 months after the surgical removal of these tumors and intensive chemotherapy. Systemic chemotherapy is recommended on patients with renal lymphoma even if the tumor seems to be limited to the organ.

Humans↗