Biomedical subjects

S Asai

Publications and source records attributed to S Asai.

At least 73 records · Page 4Linked to original sources

PubMed1999

One-step direct assay for mature-type adrenomedullin with monoclonal antibodies.

Adrenomedullin (AM) is a potent hypotensive peptide. Plasma contains mature-type AM (m-AM), which is amidated at the carboxy terminus, and an intermediate, AM-Gly. We developed a one-step two-site IRMA specific for determining human m-AM with monoclonal antibodies. The detection limit was 0.5 pmol/L, and the working range (CV <15%) was 1-300 pmol/L. Dilution of plasma samples showed good linearity. The recovery of added AM was 91-118%. The intra- and interassay imprecision values (CVs) were 4.4-8.2% and 5.5-8.3%, respectively. The assay had no cross-reactivity with AM-Gly or other peptides similar to AM. The mean (+/- SD) plasma human m-AM concentration of 61 healthy subjects was 1.18 +/- 0.65 pmol/L. In conclusion, our IRMA makes it possible to specifically measure m-AM, using a small amount of plasma sample (0.2 mL) by a one-step overnight assay without prior extraction. Our simplified method would be suitable for clinical studies on AM, especially when large numbers of samples must be processed.

Adrenomedullin↗

PubMed1998

Minimal effect of brain temperature changes on glutamate release in rat following severe global brain ischemia: a dialysis electrode study.

Using a dialysis electrode, we recently developed an oxygen-independent system for real-time measurement of the glutamate concentration in the extracellular space ([Glu]e) during ischemia. This system allows separate evaluation of intra-ischemic biphase [Glu]e elevation, i.e. release from synaptic vesicles (1st phase), reversed uptake of glutamate from metabolic pools in neuronal cells (2nd phase), and post-ischemic glutamate re-uptake in ischemia-reperfusion models. Using the system, we attempted to clarify the relationship between biphase glutamate release and brain temperature in a model of acute global ischemia produced by transecting both carotid arteries. Our results showed that, in contrast to mild hyperthermia, hypothermia did not inhibit the 1st phase of [Glu]e release, and changes in intra-ischemic brain temperature had a minimal effect on the 2nd phase of [Glu]e elevation during severe acute ischemia. These findings, together with our previous data, indicate that brain temperature change in the intra-ischemic period plays an important role in disturbance of the glutamate re-uptake system during ischemia.

Animals↗

PubMed1998

Central nervous system action of melatonin on gastric acid and pepsin secretion in pylorus-ligated rats.

We recently demonstrated that centrally administered melatonin at low doses inhibits the induction of gastric lesions by water-immersion restraint stress. To investigate the mechanism of the potent anti-ulcer action of melatonin, the central nervous system (CNS) effects of melatonin on gastric acid and pepsin secretion were studied in conscious pylorus-ligated rats. Intracisternal (i.c.) melatonin (1-100 ng) dose-dependently decreased acid and pepsin output, while a higher i.p. dose (1 microg) had no inhibitory effect. The i.c. melatonin did not change serum gastrin concentrations. Serum melatonin concentrations at 1 and 4 h after i.c. administration of 10-100 ng melatonin did not differ from those in rats receiving i.c. vehicle. The present results suggest that melatonin administered centrally modulates the secretion of gastric acid and pepsin which may explain, at least in part, the protective, anti-stress role of melatonin in the gastric mucosa observed in our previous study.

Animals↗

PubMed1998

Affinity and kinetic analysis of the molecular interaction of ICAM-1 and leukocyte function-associated antigen-1.

LFA-1 is a member of the beta2 integrin family, and interacts with ICAM-1, a member of the Ig superfamily containing five Ig-like domains. Interaction of LFA-1 with ICAM-1 is important in a number of cellular events, including Ag-specific T cell activation and leukocyte transendothelial migration, which are known to be typically transient and highly regulated. In this study, we have used surface plasmon resonance technology to study the ICAM-1/LFA-1 interaction at the molecular level. A soluble form of LFA-1 (sLFA-1), normally expressed as two noncovalently associated membrane-bound subunits, has been produced, and its interaction with ICAM-1 has been examined. The kinetic analysis of a monomeric sLFA-1 binding to the first two domains of ICAM-1 expressed as a chimeric IgG fusion protein (D1D2-IgG) revealed that sLFA-1 was bound to the D1D2-IgG chimera with a Kd of 500 nM and dissociated with a k(diss) of 0.1 s(-1). Monomeric membrane-bound LFA-1 purified from plasma membranes showed a similar kinetic to sLFA-1. These results suggest that the monovalent interaction between ICAM-1 and LFA-1 has a primarily high affinity and a slow dissociation rate constant as compared with other adhesion molecules, suggesting a potential mechanism for firm adhesion.

Animals↗

PubMed1998

Effects of brain temperature on CBF thresholds for extracellular glutamate release and reuptake in the striatum in a rat model of graded global ischemia.

We simultaneously measured extracellular glutamate ([Glu]e) elevation and local CBF using a real-time monitoring method and laser-Doppler flowmetry, respectively, in the rat striatum in a modified graded global ischemia model. Ischemic brain temperatures were kept at 32 degrees C, 37 degrees C and 39 degrees C. Three distinct types of intraischemic [Glu]e elevation, reflecting mild, moderate and massive glutamate release, were observed. Brain temperature plays an important role in determining CBF thresholds for each of the three types of [Glu]e elevation. CBF thresholds for [Glu]e elevations shifted to a lower level range as brain temperature was reduced. In mild or moderate ischemia, there is no exposure to sustained [Glu]e elevation, which is seen only in relatively severe ischemia characterized by biphasic [Glu]e elevation.

Animals↗

PubMed1998

Central nervous system action of melatonin on gastric acid and pepsin secretion in pylorus-ligated rats.

Anesthesia↗

PubMed1998

Effect of yeast extract supplementation in leach solution on bioleaching rate of pyrite by acidophilic thermophile acidianus brierleyi

The bioleaching rate of pyrite (FeS2) by the acidophilic thermophile Acidianus brierleyi was studied at 65 degrees C and pH 1.5 with leach solutions supplemented with yeast extract. In the absence of yeast extract supplementation, A. brierleyi could grow autotrophically on pyrite, and the leaching percentage of pyrite particles (25-44 μm) reached 25% for 7 d. The bacterial growth and consequent pyrite oxidation were enhanced by the addition of yeast extract between 0.005 and 0.25% w/v: the pyrite particles were completely solubilized within 6 d. The bioleaching rate was enhanced by a factor of 1.5 when the yeast extract concentration was changed from 0.005 to 0.05% w/v. However, there was only a slight effect on the leaching rate at the yeast extract concentrations of 0.05 to 0. 25% w/v, suggesting that the organic supplement level was in large excess in the pyrite bioleaching. Copyright 1998 John Wiley & Sons, Inc.

Journal Article↗

PubMed1998

An improved method for the detection of changes in brain extracellular glutamate levels.

We developed a method for in vivo real-time monitoring of the concentration of extracellular glutamate ([Glu]e) in the brain under anoxic conditions. A dialysis electrode (Sycopel Int., UK) was employed as a sensing device to measure the concentration of glutamate by enzyme amperometry, and an electron mediator, ferrocene, was introduced into the electrode together with glutamate oxidase. The ferrocene was covalently conjugated with a high molecular weight molecule, bovine serum albumin, to avoid outward diffusion through the dialysis membrane. With this set-up, the amperometric response was independent of the pO2 around the electrode in vitro up to 400 microM glutamate. Using this method, we investigated the dynamics of [Glu]e in the rat striatum during anoxia. [Glu]e increased rapidly at 102+/-5.4s (n = 6) after the start of nitrogen inhalation. The increase continued for about 30 s, and then [Glu]e decreased. The peak value of delta[Glu]e was 141+/-37 micro M. [Glu]e subsequently underwent another gradual increase, reaching 213+/-69 microM at 15 min after the start of nitrogen inhalation. This distinct biphasic profile was reproducible. We conclude that this method is very useful for monitoring [Glu]e in the brain under low pO2 conditions.

Animals↗

PubMed1998

Correlation between alcohol-induced asthma and acetaldehyde dehydrogenase-2 genotype.

BACKGROUND: Alcohol-induced asthma, a phenomenon characteristic of Asians, is due to differences in alcohol metabolism, particularly acetaldehyde metabolism. We investigated the effect of polymorphism in acetylaldehyde dehydrogenase 2 (ALDH2) gene on the response to alcohol challenge testing in a group of Japanese asthmatic subjects and normal subjects. METHODS: Subjects were 32 asthmatic subjects and 30 healthy individuals. We measured the change in FEV1 after ingestion of 30 gm of ethanol. Blood ethanol, acetylaldehyde, and histamine concentrations were determined. ALDH2 gene type was established by polymerase chain reaction. RESULTS: Ethanol provocation test results were positive in 15 (47% responders) asthmatic subjects. The blood ethanol concentration was similar in responders and nonresponders. The fall in FEV1 was associated with a rise in blood acetaldehyde and histamine concentrations. The response to oral ethanol challenge was positive in three (19%) of 16 patients with normal homozygote ALDH2 genotype, 10 (71%) of 14 patients with type mutant heterozygote, and two (100%) of two patients with type mutant homozygote ALDH2 genotype. CONCLUSIONS: Alcohol-induced asthma is probably caused by increased blood acetaldehyde concentration resulting from abnormalities of ALDH2 enzyme activity based on ALDH2 genotype differences.

Acetaldehyde↗

PubMed1998

Analysis of MYC and chromosome 8 copy number changes in gastrointestinal cancers by dual-color fluorescence in situ hybridization.

We performed dual (two-color) fluorescence in situ hybridization (FISH) by using direct fluorescent labeling probes for C-MYC and chromosome 8 in six gastrointestinal (three stomach and three colon) cancers. There are several reports of increased C-MYC copy numbers in solid tumors. To date, however, genetic rearrangements including those of the C-MYC gene have not actually been detected by FISH. Metaphase FISH demonstrated the C-MYC gene on other chromosomes (i.e., in addition to chromosome 8) in one gastric cancer. Somatic mutations such as chromosome translocation or insertion including the C-MYC gene are assumed to have occurred in this case. Our results suggest that genetic rearrangements, in addition to an increased C-MYC copy number, may be a mechanism of MYC oncogene activation in solid tumors.

Adenocarcinoma↗

PubMed1998

Effect of synthetase inhibitors and receptor antagonists in antigen-induced contraction of human lung parenchyma.

BACKGROUND: Chemical mediators induce bronchoconstriction, enhance vascular permeability, and promote inflammation. The use of synthetase inhibitors and receptor antagonists of these mediators may be useful in the treatment of asthma. OBJECTIVES: We evaluated the role of chemical mediators in mite antigen-induced contraction in resected human lung parenchyma using synthetase inhibitors and receptor antagonists for these mediators. METHODS: Resected human lung parenchymal specimens were passively sensitized with serum obtained from patients with asthma showing an IgE RAST score for mites > or = 5. The specimens were suspended in Magnus bath filled with buffer. After confirmation of contraction using PGF2 alpha, buffer or synthetase inhibitors or receptor antagonists of various chemical mediators were added. Contraction of parenchyma was induced by the addition of mite antigen, and the concentration of thromboxaneB2 (TXB2), leukotriene (LT), and histamine was measured before and after contraction. RESULTS: Thromboxane A2 (TXA2) synthetase inhibitors significantly inhibited TXB2 release but not contraction. Leukotriene synthetase inhibitors significantly inhibited both LT release and contraction. The magnitude of the inhibitory effect was in the order of LT receptor antagonist > 5-lipoxygenase inhibitor > TXA2 receptor antagonist > PAF antagonist, TXA2 synthetase inhibitor, antihistamine > cyclooxygenase inhibitor. CONCLUSION: Among chemical mediators, LT appears to be the most closely involved in the immediate antigen-induced contractile response in resected human lung parenchyma. Receptor antagonists produced a more marked inhibition of antigen-induced contraction than synthetase inhibitors.

Aged↗

PubMed1998

Comparison of three treatment regimens of inhaled sodium cromoglycate in the management of adult patients with severe, steroid-dependent asthma.

BACKGROUND: Asthmatic patients whose asthma remains poorly controlled despite treatment with high doses of inhaled corticosteroids and co-administration of oral corticosteroids are a difficult problem in therapeutics. OBJECTIVE: To investigate the relative efficacy of three treatment regimens of inhaled sodium cromoglycate in the treatment of adult, severe, corticosteroid-dependent patients as determined by the reduction in the dose of oral corticosteroids and change in lung function. METHODS: Open, randomized, group comparative trial of 12 weeks duration in asthmatic patients attending a hospital outpatient department. Patients whose asthma is (1) severe according to the classification of the Japanese Society of Allergology, (2) stable, and (3) needing treatment with at least 1600 microg of inhaled beclomethasone dipropionate and 5 mg or greater of oral prednisolone per day. The three treatment regimens of inhaled sodium cromoglycate were group A received sodium cromoglycate powder at a dose of 16 mg/day administered by a metered dose inhaler. Group N received sodium cromoglycate aqueous solution at a dose of 80 mg/day administered by a nebulizer. Group C received sodium cromoglycate aqueous solution (80 mg/day) combined with salbutamol (3 mg/day) administered by a nebulizer. The main outcome measures were a change in the daily dose of oral corticosteroids and in lung function with twice daily measurements of peak expiratory flow (PEF) recorded in the morning (PEF AM) and in the evening (PEF PM). RESULTS: Mean reduction in oral corticosteroid dose/day was group A, 3.68 mg (95% CI 1.35,5.95); group N, 3.59 mg (95% CI 0.73,6.45); and group C, 3.97 mg (95% CI 1.81,6.13). The dosage reductions are all significant but with no differences between the groups. The mean increase in PEF over the last 4 weeks of treatment compared with baseline values was significant in all groups. The increases in group C are significantly greater than those in the other groups. These changes are all significant and the increases in group C are significantly greater than those in the other groups. CONCLUSIONS: Inhaled sodium cromoglycate may be a useful additional treatment in the management of adult patients with severe, oral steroid-dependent asthma. Of the three methods of administration compared in this trial the most useful immediate results were obtained when the drug was administered as an aqueous solution mixed with salbutamol and delivered by a powered nebulizer.

Administration, Inhalation↗

PubMed1998

Protective role of melatonin and the pineal gland in modulating water immersion restraint stress ulcer in rats.

We investigated the protective effect of melatonin on stress-induced gastric lesions in rats. Fasted rats were subjected to water immersion restraint stress for 4 h and the percentage of corpus mucosa containing hemorrhagic lesions was determined. Thirty minutes before restraint stress, melatonin or vehicle was administered i.p. In another experiment, pinealectomy was performed 1 week before water immersion restraint stress. Administration of melatonin at 1 and 5 mg/kg significantly decreased gastric lesions by 46 and 74%, respectively. In contrast, pinealectomy significantly enlarged the lesion area, although this effect was counteracted by melatonin at a dose of 1 mg/kg i.p. However, this protective effect of melatonin was abolished by i.p. pretreatment with indomethacin at 5 mg/kg. These results suggest that melatonin has gastroprotective properties against stress-induced gastric injury in rats and that the pineal gland contributes to gastric protection via prostaglandin-dependent mechanisms.

Animals↗

PubMed1998

Detection of Coxiella burnetii specific DNA in blood samples from Japanese patients with chronic nonspecific symptoms by nested polymerase chain reaction.

The nested polymerase chain reaction (PCR) was used for direct species-specific detection of Coxiella burnetii in blood samples from 52 patients with chronic nonspecific symptoms, but no diagnostic or treatment history of Q fever. All patients had been in ill-health with general fatigue, muscle and joint pain, headache, etc., for one to more than 10 years. Seventeen (33%) showed evidence of C. burnetii infection, based on amplification of 438-bp fragments specific to C. burnetii by nested PCR, and 94% of positive patients reported close contact with animals. In contrast, five (9.6%) of 52 samples from healthy adult controls and two (2.8%) of 70 cord blood samples were positive by nested PCR. These data suggest a high prevalence of infection among adult patients with long term, nonspecific complaints who live in close contact with animals and the possible existence of a chronic post-acute Q fever syndrome in Japan.

Adolescent↗

PubMed1998

[A study of virulence factors produced by MRSA strains isolated from blood samples].

Toxic shock syndrome toxin-1 (TSST-1) and enterotoxins are important virulence factors produced by Staphylococcus aureus. It is reported that these toxins are associated with septic shock and toxic shock syndrome. We investigated the toxin production and coagulase types of 701 MRSA strains isolated in Sasebo City General Hospital between 1994 and 1996 TSST-1 or/and enterotoxins were detected in 67% of all MRSA strains, and those were detected in 88% of MRSA strains isolated from blood samples. 45% of all MRSA strains produced both TSST-1 and enterotoxin C, and 70% of MRSA strains obtained from blood produced those toxins. Frequency of TSST-1 or/and enterotoxin production by MRSA strains isolated from blood samples was significantly higher than that by MRSA strains isolated from urine and pharynx (p < 0.05), and frequency of both TSST-1 and enterotoxin C production by MRSA isolates from blood was significantly higher than that by MRSA strains isolated from pharyngeal sample (p < 0.05). This study indicated that investigation of virulence factors produced by MRSA might give the useful information on prevention and treatment of MRSA infection.

Bacteremia↗

PubMed1998

Astemizole-induced torsades de pointes in a patient with vasospastic angina.

Astemizole (Hismanal), an antihistamine agent, has been reported to be associated with ventricular arrhythmias. In this paper we present a case of QT prolongation and torsades de pointes (TdP) in a 77-year-old woman who had been taking astemizole (10 mg/day) for 6 months because of allergic skin disease. At the time of admission, the serum concentration of astemizole and its metabolites was markedly elevated at 15.85 ng/ml, approximately 3 times the normal level. The patient was also taking cimetidine, a known inhibitor of cytochrome P-450 enzymatic activity, and during her admission was diagnosed as having vasospastic angina. To the best of our knowledge, this is the first report of astemizole-induced QT prolongation and TdP in Japan.

Aged↗

PubMed1998

Effects of cysteinyl-leukotriene receptor antagonist, thromboxane A2 receptor antagonist, and thromboxane A2 synthetase inhibitor on antigen-induced bronchoconstriction in patients with asthma.

BACKGROUND: Leukotriene (LT) and thromboxane A2 (TXA2) receptor antagonists have been used in the treatment of asthma. OBJECTIVES: We examined the effects of an LT receptor antagonist, TXA2 receptor antagonist, and TXA2 synthetase inhibitor on bronchoprovocation test (BPT) in patients with mild-to-moderate atopic asthma. METHODS: BPT was performed four times in each of six asthmatics. Development of the immediate asthmatic reaction (IAR) and late asthmatic reaction (LAR) was confirmed on the first BPT (BPT1). After a 7-day washout period, an LT receptor antagonist (pranlukast, 450 mg/d), TXA2 receptor antagonist (seratrodast, 80 mg/d), or TXA2 synthetase inhibitor (ozagrel, 800 mg/d) was administered orally over 7 days at random using a cross-over method (BPT2-4). Blood levels of LTB4, LTC4, LTD4, 11-dehydrothromboxane B2, eosinophil cationic protein, and histamine were measured at reaction phases of pre-BPT, IAR, and LAR. RESULTS: Administration of pranlukast suppressed IAR by 80.5% (p < 0.0001) and LAR by 54.6% (p = 0.0391). Ozagrel significantly suppressed IAR by 39.5% (p = 0.0413), but the fall in FEV1 was >20% (21.56+/-4.173%). Seratrodast did not suppress IAR or LAR. Blood levels of chemical mediators did not correlate with the suppressive effects of the tested drugs. CONCLUSIONS: The LT receptor antagonist was considered to be the most effective. LT might play a more important role in the pathogenesis of asthma than TXA2. Our data showed that measurement of blood levels of chemical mediators is not useful in identifying the pathogenic mechanisms of asthma.

Administration, Oral↗

PubMed1998

[Sudden decrease in the level of consciousness due to subarachnoid bleeding attack in a patient undergoing ophthalmic surgery under retrobulbar anesthesia].

We experienced a case of intraoperative subarachnoid bleeding attack under retrobulbar anesthesia in a 71 year-old female. Immediately after retrobulbar anesthesia with bupivacaine, the patient showed a sudden decrease in her level of consciousness, respiratory depression, convulsions and her blood pressure increased to 258/63 mmHg. The clinical symptoms and onset of the attack were very similar to those of acute local anesthetic intoxication, where local anesthetics reached the central nervous system through cerebrospinal fluid or via ophthalmic artery. We gave oxygen and provided ventilatory assist by bag and mask, and administered anticonvulsant and antihypertensive agents. After we confirmed recovery of consciousness and stability of hemodynamics and respiration, the extracapsular lens extraction began. The same attack reoccurred 20 minutes later, and we treated the patient with the same procedure as in the first attack and asked the surgeon to shorten the operation. After surgery the patient was diagnosed by computed tomography as having subarachnoid bleeding from a ruptured aneurysm of the anterior cerebral artery. When a patient's level of consciousness suddenly decreases under local anesthesia, we recommend terminating the surgery to clarify the cause. In such cases, serious cardio- and cerebrovascular disorders might be involved, rather than complications due to local anesthetic intoxication.

Aged↗