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Biomedical subjects

T Ishikawa

Publications and source records attributed to T Ishikawa.

At least 325 records · Page 18Linked to original sources
PubMed2000

Atrial overdriving is beneficial in patients with atrial arrhythmias: first results of the PROVE Study.

The AF Prevention by Overdriving (PROVE) trial is an ongoing prospective study of the effectiveness of atrial overdrive pacing combined with an Automatic Rest Rate function in the prevention of atrial arrhythmias. All patients who have received a Talent DR 213 pacemaker are eligible for enrollment into the study. After a 1-month monitoring period, the patients are divided into two groups. Group I includes patients with > or = 2 appropriate mode-switch (MS) episodes, or 1 MS episode of > or = 10 minutes, and/or > 300 atrial runs of > 5 beats/month. Group II includes all other patients. The number and duration of atrial arrhythmias are measured the pacemaker's Automatic Interpretation and Data Analysis software (AIDA). Patients' quality-of-life is measured by a validated functional status questionnaire. After having been grouped, the patients are randomly assigned, in a crossover design, to standard DDDR or overdrive pacing + Rest Rate, each programmed for a 3-month period. Preliminary results in 78 patients show a 34% reduction in the mean number of MS, and a mean 48% shortening of the overall duration of the episodes by overdrive pacing + Rest Rate, achieved by a mean 84% prevalence of atrial pacing. Overdrive pacing + Rest Rate was well tolerated and associated with a slight improvement in quality-of-life.

Aged↗
PubMed2000

Diagnosis of gastric cancers: comparison of conventional radiography and digital radiography with a 4 million-pixel charge-coupled device.

PURPOSE: To evaluate the differences in accuracy and observer performance at conventional radiography and at digital radiography with a 4 million-pixel charge-coupled device (CCD) for the diagnosis of gastric cancers. MATERIALS AND METHODS: A prospective study was performed of 225 patients with suspected gastric cancer who were referred to our hospital from January 1997 through February 1997. One hundred twelve patients were examined at conventional radiography and 113 were examined at digital radiography, and 24 and 27 patients had gastric cancer, respectively. Six radiologists interpreted the images, with attention to tumor findings. They were blinded to the clinical details, and their interpretations were rated against those of three other radiologists who examined the patients and who were aware of the clinical information such as endoscopic features and/or histopathologic findings in biopsy specimens. Receiver operating characteristic (ROC) analysis was used to compare the differences in observer performance for the diagnosis of gastric cancers at conventional radiography and at digital radiography. RESULTS: The overall sensitivity was 64.6% at conventional radiography versus 75.3% at digital radiography (P =. 287); specificities were 84.5% and 90.5%, respectively (P =.011); and the positive predictive values were 53.1% and 71.3%, respectively (P =.036). ROC analysis clearly showed higher diagnostic performance at digital radiography than at conventional radiography. CONCLUSION: The data demonstrate the high diagnostic value of digital radiography with a 4 million-pixel CCD for gastric cancers. The technique has considerable potential as an alternative to conventional gastrointestinal radiography.

Biopsy↗
PubMed2000

H(2)O(2) and ethanol act synergistically to gate ryanodine receptor/calcium-release channel.

We examined the effect of low concentrations of H(2)O(2) on the Ca(2+)-release channel/ryanodine receptor (RyR) to determine if H(2)O(2) plays a physiological role in skeletal muscle function. Sarcoplasmic reticulum vesicles from frog skeletal muscle and type 1 RyRs (RyR1) purified from rabbit skeletal muscle were incorporated into lipid bilayers. Channel activity of the frog RyR was not affected by application of 4.4 mM (0.02%) ethanol. Open probability (P(o)) of such ethanol-treated RyR channels was markedly increased on subsequent addition of 10 microM H(2)O(2). Increase of H(2)O(2) to 100 microM caused a further increase in channel activity. Application of 4.4 mM ethanol to 10 microM H(2)O(2)-treated RyRs activated channel activity. Exposure to 10 or 100 microM H(2)O(2) alone, however, failed to increase P(o). Synergistic action of ethanol and H(2)O(2) was also observed on the purified RyR1 channel, which was free from FK506 binding protein (FKBP12). H(2)O(2) at 100-500 microM had no effect on purified channel activity. Application of FKBP12 to the purified RyR1 drastically decreased channel activity but did not alter the effects of ethanol and H(2)O(2). These results suggest that H(2)O(2) may play a pathophysiological, but probably not a physiological, role by directly acting on skeletal muscle RyRs in the presence of ethanol.

Acetaldehyde↗
PubMed2000

Characterization of inducible nature of MRP3 in rat liver.

We found previously that expression of multidrug resistance-associated protein (MRP) 3 is induced in a mutant rat strain (Eisai hyperbilirubinemic rats) whose canalicular multispecific organic anion transporter (cMOAT/MRP2) function is hereditarily defective and in normal Sprague-Dawley (SD) rats after ligation of the common bile duct. In the present study, the inducible nature of MRP3 was examined, using Northern and Western blot analyses, in comparison with that of other secondary active [Na(+)-taurocholic acid cotransporting polypeptide (Ntcp), organic anion transporting polypeptide 1 (oatp1), and organic cation transporter (OCT1)] and primary active [P-glycoprotein (P-gp), cMOAT/MRP2, and MRP6] transporters. alpha-Naphthylisothiocyanate treatment and common bile duct ligation induced expression of P-gp and MRP3, whereas expression of Ntcp, oatp1, and OCT1 was reduced by the same treatment. Although expression of MRP3 was also induced by administration of phenobarbital, that of cMOAT/MRP2, MRP1, and MRP6 was not affected by any of these treatments. Moreover, the mRNA level of MRP3, but not that of P-gp, was increased in SD rats after administration of bilirubin and in Gunn rats whose hepatic bilirubin concentration is elevated because of a defect in the expression of UDP-glucuronosyl transferase. However, the MRP3 protein level was not affected by bilirubin administration. Although the increased MRP3 mRNA level was associated with the increased concentration of bilirubin and/or its glucuronides in mutant rats and in SD rats that had undergone common bile duct ligation or alpha-naphthylisothiocyanate treatment, we must assume that factor(s) other than these physiological substances are also involved in the increased protein level of MRP3.

1-Naphthylisothiocyanate↗
PubMed2000

Reward linked to increased natural killer cell activity in rats.

In rats splenic natural killer (NK) cell activity was found to be significantly higher following chronic uncontrollable electrical stimulation of the lateral hypothalamus in fully conscious rats, compared to sham-operated rats. In a pre-test study, all rats had demonstrated that the electrode site had self-stimulating properties, which supports the possibility that the experience of reward may be implicated in NK cell activity augmentation.

Animals↗
PubMed2000

Brain natriuretic peptide is a predictor of anthracycline-induced cardiotoxicity.

Anthracyclines are effective antineoplastic drugs, but they frequently cause dose-related cardiotoxicity. The cardiotoxicity of conventional anthracycline therapy highlights a need to search for methods that are highly sensitive and capable of predicting cardiac dysfunction. We measured the plasma level of brain natriuretic peptide (BNP) to determine whether BNP might serve as a simple diagnostic indicator of anthracycline-induced cardiotoxicity in patients with acute leukemia treated with a daunorubicin (DNR)-containing regimen. Thirteen patients with acute leukemia were treated with a DNR-containing regimen. Cardiac functions were evaluated with radionuclide angiography before chemotherapies. The plasma levels of atrial natriuretic peptide (ANP) and BNP were measured at the time of radionuclide angiography. Three patients developed congestive heart failure after the completion of chemotherapy. Five patients were diagnosed as having subclinical heart failure after the completion of chemotherapy. The plasma levels of BNP in all the patients with clinical and subclinical heart failure increased above the normal limit (40 pg/ml) before the detection of clinical or subclinical heart failure by radionuclide angiography. On the other hand, BNP did not increase in the patients without heart failure given DNR, even at more than 700 mg/m(2). The plasma level of ANP did not always increase in all the patients with clinical and subclinical heart failure. These preliminary results suggest that BNP may be useful as an early and sensitive indicator of anthracycline-induced cardiotoxicity.

Acute Disease↗
PubMed2000

Developmental changes in collapsibility of the passive pharynx during infancy.

The upper airway configuration significantly changes during the first year of life in humans, possibly leading to alteration of collapsibility of the pharyngeal airway. The present study evaluated developmental changes of passive pharyngeal mechanics in nine normal infants ranging in age from 2 to 12 mo. The static pressure-area relationship of the passive pharynx was quantified under general anesthesia with complete paralysis. We found a direct association between age and maximal velopharyngeal area (r = 0.840, p = 0.005). Velopharyngeal closing pressure progressively decreased with increasing age (r = -0.809, p = 0.008) and the closing pressures were below atmospheric pressure in all infants (range: -0.7 to -9.8 cm H(2)O; mean +/- SD: -3.6 +/- 2.7 cm H(2)O). Shape of the pressure-area curves became steeper in slope with maturation, indicating increased pharyngeal wall stiffness during development. Accordingly, we conclude that anatomic properties of the pharynx gain stability in favor of maintaining patent airway during development in normal infants.

Airway Resistance↗
PubMed2000

ADAMTS-1: a metalloproteinase-disintegrin essential for normal growth, fertility, and organ morphology and function.

A disintegrin and metalloproteinase (ADAM) represents a protein family possessing both metalloproteinase and disintegrin domains. ADAMTS-1, an ADAM family member cloned from cachexigenic colon adenocarcinoma, is unusual in that it contains thrombospondin type I motifs and anchors to the extracellular matrix. To elucidate the biological role of ADAMTS-1, we developed ADAMTS-1-null mice by gene targeting. Targeted disruption of the mouse ADAMTS-1 gene resulted in growth retardation with adipose tissue malformation. Impaired female fertilization accompanied by histological changes in the uterus and ovaries also resulted. Furthermore, ADAMTS-1(-/-) mice demonstrated enlarged renal calices with fibrotic changes from the ureteropelvic junction through the ureter, and abnormal adrenal medullary architecture without capillary formation. ADAMTS-1 thus appears necessary for normal growth, fertility, and organ morphology and function. Moreover, the resemblance of the renal phenotype to human ureteropelvic junction obstruction may provide a clue to the pathogenesis of this common congenital disease.

ADAM Proteins↗
PubMed2000

Persistent increase in bone turnover in Graves' patients with subclinical hyperthyroidism.

Hyperthyroid patients exhibit accelerated bone loss by increased bone turnover, and normalization of thyroid function is associated with a significant attenuation of increased bone turnover, followed by an increase in bone mineral density. However, of patients with Graves' disease (GD) maintained on antithyroid drug (ATD) treatment, some exhibit persistent suppression of TSH long after normalization of their serum free T3 (FT3) and free T4 (FT4) levels. The aim of this study was to examine whether bone metabolism is still enhanced in TSH-suppressed premenopausal GD patients with normal FT3 and FT4 levels after ATD therapy (n = 19) compared with that in TSH-normal premenopausal GD patients (n = 30), and to evaluate the relationship between serum TSH receptor antibody (TRAb), an indicator of disease activity of GD, and various biochemical markers of bone metabolism. No difference was found between the two groups in serum Ca, phosphorus, or intact PTH, or in urinary Ca excretion. Serum bone alkaline phosphatase (B-ALP), bone formation markers, and urinary excretions of pyridinoline (U-PYD) and deoxypyridinoline (U-DPD), which are bone resorption markers, were significantly higher in the TSH-suppression group than in the TSH-normal group (B-ALP, P < 0.05; U-PYD, P < 0.001; U-DPD, P < 0.001). For the group of all GD patients enrolled in this study, TSH, but neither FT3 nor FT4, exhibited a significant negative correlation with B-ALP (r = -0.300; P < 0.05), U-PYD (r = -0.389; P < 0.05), and U-DPD (r = -0.446; P < 0.05), whereas TRAb exhibited a highly positive and significant correlation with B-ALP (r = 0.566; P < 0.0001), U-PYD (r = 0.491; P < 0.001), and U-DPD (r = 0.549; P < 0.0001). Even in GD patients with normal TSH, serum TRAb was positively correlated with B-ALP (r = 0.638; P < 0.001), U-PYD (r = 0.638; P < 0.001), and U-DPD (r = 0.641; P < 0.001). In conclusion, it is important to achieve normal TSH levels during ATD therapy to normalize bone turnover. TRAb was not only a useful marker for GD activity, but was also a very sensitive marker for bone metabolism in GD patients during ATD treatment.

Adult↗
PubMed2000

Synthesis and pharmacological activity of O-(5-isoxazolyl)-L-serine.

A novel isoxazole derivative, O-(5-isoxazolyl)-L-serine (OIS, 1), was synthesized by a Mitsunobu reaction of isoxazolin-5-one (4) with N-Boc-L-serine tert-butyl ester (5) and subsequent deprotection of the coupling product. Its structure was elucidated by spectroscopic analyses. The pharmacological activity of 1 was also examined with cloned glutamate receptors and transporters using a Xenopus oocyte-expressing system showing substrate activity on an excitatory amino acid carrier 1 (EAAC 1) as a glutamate transporter.

ATP-Binding Cassette Transporters↗
PubMed2000

Prevalence of migraine and Raynaud's phenomenon in Japanese patients with vasospastic angina.

The prevalence of migraine and Raynaud's phenomenon in Japanese patients with vasospastic angina (group I) were compared with those in 2 control groups: one with effort angina (group II) and the other group without known ischemic heart disease (group III). There were no significant differences among the 3 groups with respect to age and sex. The prevalence of migraine in group I was 23 of 100, as compared with 4 of 100 in group II (p<0.01) and 11 of 100 in group III (p<0.05). The prevalence of Raynaud's phenomenon in group I was 9 of 100, as compared with 3 of 100 in group II and 4 of 100 in group III. Thus, in Japan, the prevalence of migraine in patients with vasospastic angina was higher than those in the 2 control groups, whereas the prevalence of Raynaud's phenomenon did not differ significantly among the 3 groups. The prevalence of Raynaud's phenomenon in Japanese patients with vasospastic angina was different from that reported from North America, although the prevalence of migraine was the same. This may be partially explained by racial differences.

Aged↗
PubMed2000

Incidence of atrial flutter and atrial fibrillation in patients with implanted physiological pacemakers.

Atrial flutter (AF) is a troublesome arrhythmia for patients with an implanted pacemaker. Although it has recently become possible to eliminate AF by radiofrequency catheter ablation (RF-CA), the incidence of AF before and after pacemaker implantation has not been clarified. The present study was conducted with 123 consecutive patients (69.3+/-11.6 (SD) years old) implanted with pacemakers, excluding patients who had chronic atrial fibrillation (AFib) when the pacemaker was implanted; 69 patients with atrioventricular (AV) block and 54 patients with sick sinus syndrome (including 29 patients with bradycardia-tachycardia syndrome). All patients were implanted with physiological pacemakers. The follow-up period was 4.7+/-1.9 years. In 11 of the 123 patients (8.9%), AF was observed before pacemaker implantation and the incidence was significantly higher in patients with sick sinus syndrome than in those with AV block (16.7 vs 2.9%, p<0.01). Nine of the 29 patients with bradycardia-tachycardia syndrome (31%) had AF. After physiological pacemaker implantation, AF recurred in 9 of the 11 patients, and AF was newly observed in 1 patient. Thus, 10 of the 123 patients (8.1%) had AF after physiological pacemaker implantation. Recurrence of AF was not suppressed by physiological pacing. Thirty of the 123 patients had AFib before implantation of a pacemaker and its occurrence was reduced by physiological pacing (from 24.4% to 12.2%, p<0.05). The incidence of AFib in patients with AF was significantly higher than in those without AF (90.0 vs 5.3%, p<0.001). In conclusion, the recurrence of AF is not prevented by physiological pacing and is closely related to the occurrence of AFib. RF-CA should be considered in patients who have AF before pacemaker implantation.

Aged↗
PubMed2000

Efficacy of atrioventricular sequential pacing and diastolic mitral regurgitation in patients with intrinsic atrioventricular conduction.

The efficacy of a short atrioventricular (AV) delay in patients with dilated cardiomyopathy has been reported, but there are deleterious effects of right ventricular pacing. Diastolic mitral regurgitation (MR) is observed in patients with elevated left ventricular end-diastolic pressure and can be induced by prolonging the AV delay in patients with DDD pacemakers. The critical PQ interval that induces diastolic MR may represent the upper limit of the optimal PQ interval. The efficacy of AV sequential pacing and diastolic MR were studied in 11 patients (68.3+/-13.7 (SD) years old) with intrinsic AV conduction and with implanted DDD pacemakers. Cardiac output (CO) and pulmonary capillary wedge pressure (PCWP) were measured by Swan-Ganz catheter and transmitral flow was recorded by pulsed Doppler echocardiography. AV delay was prolonged stepwise by 25 ms starting from 65 ms. Pacing rate was fixed at 70-80 beats/min. In 6 of the 11 patients, diastolic MR was observed under atrial pacing and the critical PQ interval for the appearance of diastolic MR was 0.22+/-0.04 s. CO was increased from 3.8+/-0.8 to 4.3+/-0.9 L/min (p<0.05) and PCWP was decreased from 7.5+/-2.8 to 5.5+/-1.6 mmHg (p<0.05) by shortening the AV delay till the diastolic MR disappeared. On the other hand, in 5 of the 11 patients, diastolic MR was not observed, and CO (4.2+/-0.5 to 4.3+/-0.5L/min, ns) and PCWP (5.8+/-4.6 to 5.4+/-3.9 mmHg, ns) were not improved by AV sequential pacing. In conclusion, cardiac function may be improved by AV sequential pacing and setting the AV delay under the critical PQ interval for the appearance of diastolic MR when the diastolic MR is observed. However, AV sequential pacing may be either ineffective or even deleterious for patients in whom diastolic MR is not observed.

Aged↗
PubMed2000

Application of a newly developed photoluminescence glass dosimeter for measuring the absorbed dose in individual mice exposed to low-dose rate 137Cs gamma-rays.

A photoluminescence glass dosimeter, GD-301, was applied to the measurement of low absorbed doses in mice exposed to low-dose rate 137Cs gamma-rays. The dosimeter system consists of small rod-shaped glass chip detectors capable of embedded in the body of a mouse and an automatic readout device equipped with a standard detector irradiated with 137Cs gamma-source. The measured absorbed doses were compared with the "exposure" estimated by an ionization chamber and with the doses measured by a BeO:Na thermoluminescence system. The results clearly demonstrate the superiority of the glass dosimetry regarding simplicity of operation, stability of long-term dose accumulation and good detector uniformity, which allow accurate tissue dosimetry.

Animals↗
PubMed2000

Radical-capturing reaction of 5,7,3',4'-tetramethylquercetin with the AIBN radical initiator.

In order to clarify the mechanism for the radical-capturing reaction which is initiated at the C3-hydroxyl group of flavonols, 5,7,3',4'-tetramethylquercetin (TMQ) was reacted with the 2,2'-azobis-isobutyronitrile (AIBN) radical initiator in benzene. Six products, one depside and its two hydrolytic products, one nitrile adduct, and two others, were isolated from the reaction mixture, and their structures were determined by instrumental analyses. The quantitative change to the four main products against the reaction time was measured by an HPLC method. The radical-capturing reaction pathway for TMQ with AIBN is proposed from these products and their quantitative changes. The pathway dividing into two clearly reveals that one subpath formed the depside and its hydrolytic products, while the other formed the nitrile adduct. The reactivity of each two sub-path was nearly the same, different from the case of TMQ and the 2,2'-azobis-2,4-dimethylvaleronitrile (AMVN) radical initiator.

Benzene↗
PubMed2000

Genetic analysis of growth inhibition of yeast cells caused by expression of Aspergillus oryzae RNase T1.

Even though most fungal hydrolytic enzymes have been successfully secreted in S. cerevisiae cells by expression of corresponding cDNA, overexpression of A. oryzae RNase T1 causes severe growth inhibition in yeast. We observed that yeast strains carrying RNase T1 cDNA under control of the GAL1 promoter with a single-copy vector were able to grow on galactose medium while those with a multi-copy vector were not. It was found that overexpression of three mutated versions of RNase T1 with low enzymatic activity did not affect the growth. We also observed that expression of RNase T1 without a signal sequence severely inhibited growth of the transformant even on the single-copy plasmid. Subcellular fractionation showed that overexpressed myc-tagged RNase T1 was localized in the membrane fraction. In the yeast secretory pathway, while the mutants defective in translocation into the ER, ER-Golgi trafficking and vacuole formation had severe growth inhibition during expression of RNase T1 from the single-copy plasmid. These results suggest that a mislocalization of active RNase T1 in cytosol by overflow from the secretory apparatus has toxic effects on the host cells.

Aspergillus oryzae↗
PubMed2000

Plasma levels and redox status of ascorbic acid and levels of lipid peroxidation products in active and passive smokers.

Both active and passive smoking are regarded as risk factors for various diseases. To clarify the effects of active and passive smoking on plasma vitamin C levels and lipid peroxidation status, we examined the plasma levels of ascorbic acid (AA), its redox status [ratio of dehydroascorbate (DHAA) to total AA], the levels of thiobarbiturate reactive substance (TBARS), and the levels of lipid peroxides (LPO) in smokers, nonsmokers, and nonsmokers regularly exposed to environmental cigarette smoke (passive smokers). The study population consisted of 149 healthy males: 75 active smokers (consumption of > 15 cigarettes/day for more than 5 years), 36 passive smokers (more than 10 hr/week exposure to environmental cigarette smoke), and 38 nonsmokers (no cigarette smoke exposure). There were no significant differences in plasma TBARS and LPO levels among the three groups. Plasma levels of AA, the reduced form of vitamin C, were significantly lower in active smokers than in the combined nonsmoking groups (7.2 +/- 3.5 and 8.4 +/- 3.4 microg/mL, respectively; p < 0.05). Although no significant differences were found in plasma DHAA levels among the three groups, the ratios of DHAA to total AA were significantly higher in active and passive smokers than nonexposed nonsmokers (11.2, 10.3, and 7.1%, respectively; p < 0.05). These results indicate that passive smoking, as well as direct inhalation of cigarette smoke, affects the redox status of plasma AA. In passive smokers, the altered redox status of plasma AA suggests an oxidative stress.

Adult↗