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Biomedical subjects

T Shindo

Publications and source records attributed to T Shindo.

At least 55 records · Page 3Linked to original sources
PubMed1997

[Gene Polymorphism of 5, 10-methylenetetrahydrofolate reductase as a coronary risk factor].

Hyperhomocysteinemia has been identified as a possible risk factor for coronary artery disease. The association of the alanine/valine (A/V) polymorphism of 5, 10-methylenetetrahydrofolate reductase (MTHFR), one of the key enzymes catalyzing re-methylation of homocysteine, with coronary artery disease was examined in 362 Japanese males with a diagnosis of coronary artery disease confirmed with coronary angiography. The A/V polymorphism was analyzed with PCR followed by Hinf I digestion. The screening of 778 male volunteer controls revealed that the frequency of V allele in Japanese was 0.33, comparable to that in the French Canadian population. The VV genotype, which correlates with increased plasma homocysteine levels due to reduced activity and increased thermolability of this enzyme, was significantly more frequent in patients with coronary artery disease (15.7%, n = 362) than in controls (10.2%, n = 778; p = 0.0067). The association of the VV genotype with coronary artery disease was further increased in patients with > or = 99% stenotic lesion (p = 0.0010). In these patients, the frequency of the VV genotype was significantly higher in patients with triple-vessel disease (26%) than in patients with single- or double-vessel disease (15% and 14%, respectively). The fasting plasma homocysteine levels in VV subjects were higher than those in AV or AA subjects. The VV genotype of MTHFR associated with increased plasma homocysteine levels may represent an important genetic risk factor for coronary artery disease, especially with the occurrence of myocardial infarction.

Adult↗
PubMed1996

Cough threshold for capsaicin increases by azelastine in patients with cough-variant asthma.

To assess the effects of azelastine in patients with cough-variant asthma, we measured the cough threshold for capsaicin (the concentration required to elicit more than five coughs) in 16 patients with cough-variant asthma before and after 4 weeks of treatment with azelastine (2 mg; b.i.d.) or placebo. After treatment, coughing decreased in all patients and the cough threshold for capsaicin increased significantly, from 0.67 +/- 0.30 microM to 4.76 +/- 1.55 microM (P < 0.01) in the azelastine group. However, the cough threshold for capsaicin did not increase significantly, from 0.86 +/- 0.33 microM to 1.11 +/- 0.35 microM (P > 0.10) in the placebo group. These results suggest that azelastine inhibits coughing in patients with cough-variant asthma.

Adult↗
PubMed1996

Antimuscarinic effect of tiquizium bromide in vitro and in vivo.

OBJECTIVE: We studied the bronchodilatory effect of tiquizium bromide [3-(di-2-thienylmethylene)-5 methyl-trans-quinolizidinium bromide; TQZ], an antimuscarinic agent, on airway smooth muscle in vitro, and also in patients with chronic obstructive pulmonary disease (COPD). METHODS: In the first experiment, canine tracheal smooth muscle was used to measure the pA2 of TQZ in vitro. The selectivity of TQZ in vitro. The selectivity of TQZ for muscarinic receptor subtypes was also examined with a radioligand binding assay. RESULTS: The pA2 value of TQZ was 8.75. The pKi values of TQZ for M1, M2, and M3 were 8.70, 8.94, and 9.11, respectively. In an open pilot experiment, the effects of TQz inhalation were studied in seven patients with COPD (seven men, mean age 68.5 years). TQZ significantly increased forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) in a dose-dependent manner. The mean maximum increases in FVC and FEV1 caused by inhaled TQZ (2.0 mg) were 24% and 29%, respectively, and they were measured 1 h after the drug had been inhaled. The FVC and FEV1 were still significantly higher than the control values even 8 h after the drug had been inhaled. No adverse effects were observed after inhalation of TQZ. CONCLUSION: These data suggest that TQZ is an effective antimuscarinic agent, and that it causes significant bronchodilation in patients with COPD.

Acetylcholine↗
PubMed1996

Regional myocardial interstitial norepinephrine kinetics during coronary occlusion and reperfusion.

We investigated myocardial interstitial norepinephrine kinetics in both the ischemic and nonischemic regions during reperfusion after 40 min of coronary occlusion in anesthetized cats. By use of a cardiac dialysis technique, dialysate norepinephrine contents from both regions were monitored as an index of myocardial interstitial norepinephrine levels. For vehicle perfusate (n = 8), the accumulated dialysate norepinephrine level in the postischemic region decreased from 3,010 +/- 923 pg/ml at 30-40 min of occlusion to 957 +/- 178 pg/ml at 0-10 min of reperfusion and returned to near control level at 30-40 min of reperfusion. After 40 min of reperfusion, there were no significant differences in tyramine (100 micrograms/ml, norepinephrine-releasing sympathomimetic amine)-induced norepinephrine release between both regions. For perfusate containing 100 microM desipramine (neural uptake inhibitor, n = 6), at 0-10 min of reperfusion, the dialysate norepinephrine in the postischemic region did not significantly decrease. The dialysate norepinephrine then returned to near preocclusion level at 30-40 min of reperfusion. These data suggest that reperfusion rapidly returns accumulated myocardial norepinephrine to the preischemic level and neuronal norepinephrine uptake greatly contributes to this return in the early phase of reperfusion. Forty minutes of coronary occlusion cause neither norepinephrine exhaustion nor irreversible impairment of norepinephrine uptake function in nerve terminals.

Animals↗
PubMed1996

Method of obtaining mutants defective in immunoglobulin mu transcription factors.

A method of obtaining mutants defective in the regulatory function of Ig mu gene expression was developed. Such mutants are useful for discovering the functions of transcription factors and isolating their genes, especially those of DNA-unbinding factors. Cells expressing Ig mu and Eco-GPT simultaneously under control of each mu enhancer were prepared as follows: myeloma X63Ag8.653 cells were transfected with pSV-V mu Me delta CH1 encoding a mu gene modified for cell surface mu expression without light chains, selected by neomycin resistance, transfected with Eco-GPT gene connected to the mu enhancer, and selected with mycophenolic acid in a medium containing xanthine. The mu(m)/Eco-GPT cells were mutated with ethane methyl sulfonate (EMS), and selected with toxin-conjugated anti-mu antibody, and then with 6-thioguanine. The mu(M)-/Eco-GPT- mutants obtained were fused with X63Ag8.653 cells. Fusion caused the mutant to recover mu(M) expression, suggesting that some trans-acting transcription factor other than the mu-encoding gene itself was probably mutated.

3T3 Cells↗
PubMed1996

Effectiveness of the anticholinergic agent oxitropium bromide in elderly patients with bronchial asthma.

The short-term and long-term effects of the anticholinergic agent oxitropium bromide (CAS 30286-75-0, OTB) were studied in nine elderly patients with bronchial asthma (8 men and 1 women, age: 69.5 +/- 5.2 years, 3 atopic and 6 (not atopic cases). 2 h after inhalation of 0.8 mg of OTB, forced vital capacity (FVC) had increased from 2.28 +/- 0.22 1 to 2.87 +/- 0.27 1 (p < 0.01), forced expiratory volume in 1 s (FEV1) had increased from 1.22 +/- 0.14 to 1.57 +/- 0.16 1 (p < 0.01), and respiratory resistance (Rrs) had decreased from 5.9 +/- 0.8 cmH2O/l/s to 4.9 +/- 0.7 cmH2O/l/s (p < 0.05). The patients inhaled OTB (0.2 mg t.i.d.) for 6 weeks. Their peak expiratory flow rates, measured each morning and each evening, increased significantly during the first 2 weeks of administration, and the increase was sustained for the entire weeks (p < 0.05). Other pulmonary-function tests were done before drug administration and again at the end of the 6 weeks. By the end of the 6th week of OTB administration, FVC had increased from 2.30 +/- 0.22 1 to 2.99 +/- 0.26 1 (p < 0.01), and FEV1 had increased from 1.25 +/- 0.17 to 1.70 +/- 0.22 1 (p < 0.05). These data indicate that OTB can be useful in the treatment of elderly patients with bronchial asthma.

Administration, Inhalation↗
PubMed1995

Routine high-performance liquid chromatographic determination of myocardial interstitial norepinephrine.

The present study describes a high-performance liquid chromatographic-electrochemical detection (HPLC-ED) system for routine measurement of the low levels of norepinephrine (NE) found in the myocardial interstitial space. In this system, an in vivo detection limit of 100 fg in a 50-microliters injection was achieved for NE. Using cardiac dialysis technique, 20-microliters dialysates were sampled from the myocardial interstitial space at 2-min intervals. The basal dialysate NE concentration was 16.6 +/- 4.0 pg/ml. This low detection limit allowed the dialysate NE concentration to be monitored for dysfunction of the cardiac sympathetic nerve terminal. This system offers a new possibility for routine analysis of myocardial interstitial NE levels.

Animals↗
PubMed1995

Systemic artery-to-pulmonary artery shunt after using an omental pedicle flap.

A 66-year-old man was hospitalized because of hemoptysis. Four years earlier, he had undergone an operation involving the use of an omental pedicle flap that was supplied by the right gastroepiploic artery for the treatment of empyema. Arteriography revealed that the right gastroepiploic artery communicated with the periphery of the right pulmonary artery. The right gastroepiploic artery was divided surgically.

Abdominal Muscles↗
PubMed1995

A catechol 2,3-dioxygenase gene as a reporter.

A catechol 2,3-dioxygenase (C23O) gene of Pseudomonas aeruginosa was expressed under the Simian virus 40 or Rous sarcoma virus promoter in mammalian cells; it was found that the gene could be used as a reporter for the study of gene expression. The C23O gene was a more sensitive reporter than the generally used beta-galactosidase gene.

Amino Acid Sequence↗
PubMed1995

Aneurysmal dilatation of the pulmonary trunk with mild pulmonic stenosis.

We present the unusual case of a 72-year-old woman whose chest X-ray showed an abnormal left hilar shadow. A pulmonary angiogram revealed an aneurysm in the pulmonary artery with a diameter of 55 mm that extended from the main pulmonary trunk to its bifurcation. Mild pulmonic stenosis with a systolic pressure gradient of 18 mmHg across the pulmonic valve was recognized. Mild dilatation of the ascending aorta was also present. The pressure gradient across the pulmonic valve was lower than is typical for an aneurysmal dilatation, suggesting that this patient represented a case of idiopathic pulmonary artery dilatation. We suspected the presence of a congenital structural alteration common to the pulmonary artery and the ascending aorta.

Aged↗
PubMed1995

Nitric oxide synthesis in cardiac myocytes and fibroblasts by inflammatory cytokines.

OBJECTIVE: The aim was to investigate nitric oxide (NO) synthase activity in cultured neonatal rat cardiac myocytes and fibroblasts upon treatment with inflammatory cytokines interleukin 1 beta (IL-1 beta), tumour necrosis factor alpha (TNF-alpha), IL-2, IL-6, IL-8, transforming growth factor beta (TGF-beta) and gram negative bacterial lipopolysaccharide (LPS). METHODS: NO and guanosine 3',5'-cyclic monophosphate (cGMP) synthesis was measured in cultured neonatal rat cardiac myocytes and fibroblasts, using Griess reagent and an enzyme immunoassay kit, respectively. The expression of inducible NO synthase (iNOS) mRNA and protein was assayed by northern and western blotting, respectively. RESULTS: Incubation of cardiac myocytes for 24 h with IL-1 beta (10 ng.ml-1) or LPS (1 microgram.ml-1) caused significant increases in NO and cGMP production. TNF-alpha, IL-2, IL-6, IL-8, and TGF-beta showed no significant effect on their production. IL-1 beta induced NO and cGMP production in a time and dose dependent manner. IL-1 beta also increased iNOS mRNA and protein accumulation in cardiac myocytes. Simultaneous incubation of IL-1 beta with NG-monomethyl-L-arginine, genistein, calphostin C, cycloheximide, or actinomycin D completely inhibited the IL-1 beta induced NO production by cardiac myocytes. TGF-beta, dexamethasone, or cyclosporin A also dose dependently inhibited the IL-1 beta induced NO production. Exposure to IL-1 beta for 12-24 h decreased the beating rate of cardiac myocytes, but addition of dexamethasone completely overcame this inhibition. In contrast to cardiac myocytes, incubation of cardiac fibroblasts for 24 h with IL-1 beta or LPS showed no significant effect on NO or cGMP production. CONCLUSIONS: These observations suggest that IL-1 beta/LPS responsive iNOS, which is an important regulator of contractile function of the heart, is present in cardiac myocytes but not in cardiac fibroblasts.

Amino Acid Oxidoreductases↗
PubMed1995

[Female lung cancer].

One hundred and ninety one women were diagnosed with lung cancer at our hospital. This comprised 23.7% of all lung cancer cases. Smoking habits were significantly lower in female lung cancer. Adenocarcinoma is the most common histological type of female lung cancer (64.2%). The prognoses of asymptomatic cases detected by regular examination were significantly better than those of symptomatic cases. Among resectable cases of either adenocarcinoma or squamous cell carcinoma, there were no significant differences between the prognosis for women and that for men. However, the prognosis for nonresectable cases of adenocarcinoma in women was significantly better in the 2-year survival rate (30.8%) than the prognosis for such cases in men. Since the periphery type is the most common site of adenocarcinoma in women, educating women, especially those in the high-risk group, and persuading them to undergo regular examinations are important step to increasing early-stage detection and cure.

Adenocarcinoma↗
PubMed1995

Effect of a new dual neurokinin antagonist on airway smooth muscle in situ.

The effect of FK224 (N-(N2-[N-¿N-(N-2,3-didehydro-N-methyl-N-[N-3- (2-pentylphenyl)-propionyl¿-L-threonyl]tyrosyl-L-leucynyl)-D -phenylalanyl¿-L-allothreonyl]-L-asparaginyl)-L-serine-v-lacto ne, CAS 125787-94-2) on isometric contraction of canine tracheal smooth muscle in situ was studied. Contraction was induced by administration of substance P, neurokinin A, and neurokinin B intra-arterially into the tracheal circulation in five mongrel dogs. FK224 inhibited substance P- and neurokinin A-induced contraction in a dose-dependent manner, but it did not inhibit neurokinin B-induced contraction significantly. These data suggest that FK224 is a dual antagonist of both neurokinin 1 and neurokinin 2 receptors, with a similar potency in in vivo experiments.

Animals↗
PubMed1994

Diameter and flow velocity changes of feline small pulmonary vessels in response to sympathetic nerve stimulation.

Using an X-ray television system, we measured directly changes in the internal diameter (ID), flow velocity, and volume flow of the small pulmonary vessels (100-500 microns ID) in response to electrical sympathetic nerve stimulation (SNS) in anaesthetized cats before and after adrenergic receptor blockade. Flow velocity was obtained by measuring the distance that the leading edge of the contrast medium moved per 0.1 s in the small arteries. Volume flow was obtained from the product of flow velocity and cross-sectional area calculated from the ID of the small arteries. SNS was accomplished with 10- to 15-V square-wave pulses of 2-ms duration at 20-30 Hz for 20-s periods. In response to SNS, arterial ID decreased significantly by 8-13% in the 200- to 500-microns vessels but not in the 100- to 200-microns vessels. In the veins, on the other hand, there was no significant ID decrease in any of the 100- to 500-microns vessels. After alpha-receptor blockade (phentolamine, 2 mg/kg i.v.), there were significant ID increases (4-9%) in the 100- to 500-microns arteries in response to SNS, the maximum increases being in the 100- to 200-microns arteries. After beta-blockade (propranolol, 2 mg/kg i.v.), the ID decrease due to SNS in the 200- to 500-microns arteries was enhanced (24-27%) and, in addition, the 100- to 200-microns arteries exhibited a significant ID decrease (18%). Combined alpha- and beta-blockade completely abolished the ID decrease due to SNS. In the veins, on the other hand, no ID change occurred even after alpha- or beta-blockade.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗