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H Toda

Publications and source records attributed to H Toda.

At least 55 records · Page 3Linked to original sources

[Clinical trial of fadrozole hydrochloride for postmenopausal patients with recurrent breast cancer].

Eleven recurrent postmenopausal breast cancer patients with osseous or lung metastases were received fadrozole hydrochloride at a dose of 1 mg twice a day for more than 8 weeks. The median disease-free interval of these 11 patients with metastasis was 74 months. Out of 11 evaluable cases, 2 PR, 6 long-NC and 3 PD were observed. The overall response rate was 18.2% and the long-NC rate was 54.5%. The average overall duration of responses and long-NC were 567 days and 573 days, respectively. There was no adverse drug reaction. A combination therapy with fadrozole hydrochloride 2 mg daily and cyclophosphamide 100 mg orally on days 1-14 was given to 14 postmenopausal patients with recurrent breast cancer. The median disease-free interval of these 14 patients with metastasis was 33 months. There were 2 CR, 3 PR, 4 long-NC, 2 NC and 3 PD. The overall response rate and long-NC rate were 35.8% and 28.6%, respectively. The average overall duration of responses and long-NC were 700 days and 443 days, respectively. The adverse drug reactions were anorexia (Grade 2) and neutropenia (Grade 1 and 2). These results suggested that a combination therapy with fadrozole hydrochloride and cyclophosphamide can be effective and contribute to survival time in the treatment of postmenopausal breast cancer.

Aged↗

Cardioprotection of SM-15681, an Na+/H+ exchange inhibitor in ischemic and hypoxic isolated perfused rat hearts.

We investigated the effects of SM-15681 (N-(aminoiminomethyl)-1-methyl-1H-indole-2-carboxamide monohydrochloride) on Na+/H+ exchange activity in the myocardium and in ischemic and hypoxic injury in isolated perfused rat hearts. These effects were compared with those of ethylisopropyl amiloride (EIPA). Na+/H+ exchange activity was studied with a NH4Cl prepulse technique under HCO3(-)-free conditions. SM-15681 (10(-8)-10(-7) M) inhibited pH recovery of acidosis in the rat myocardium in a concentration-dependent manner and the IC50 value of SM-15681 (80 nM) was similar to that of EIPA. In perfused rat hearts, SM-15681 (10(-6) M) and EIPA (10(-6) M) significantly improved cardiac functions and prevented enzyme release and abnormal elevation of tissue Ca2+ content during 20 min of reperfusion after 40 min of ischemia and 20 min of reoxygenation after 30 min of hypoxia. We conclude that an Na+/H+ exchange inhibitor, SM-15681, shows cardioprotective effects on ischemia/reperfusion and hypoxia/reoxygenation injury. Our results also support the hypothesis that Na+/H+ exchange contributes to the pathophysiology of cardiac ischemic reperfusion injury.

Amides↗

Thiopental attenuates relaxation and cyclic GMP production in vascular smooth muscle of endotoxin-treated rat aorta, independent of nitric oxide production.

As thiopental (thiopentone) suppresses cyclic GMP (cGMP) formation produced by nitric oxide donor drugs, we have tested if it suppresses cGMP formation and increases vascular tone after induction of calcium-calmodulin-independent nitric oxide synthase (iNOS). Rat aortic rings were treated with Escherichia coli lipopolysaccharide (LPS) 1 microgram ml-1 for 4 h, and the effects of thiopental on tension, cGMP concentrations and nitrite accumulation were determined. Thiopental 0.3 mmol litre-1 reduced the tension of phenylephrine-precontracted aortic rings before LPS treatment, but caused no significant effects on tension in the presence of L-arginine 10 mumol litre-1 after LPS treatment. L-Arginine 1 mumol litre-1 to 1 mmol litre-1 increased concentrations of cGMP in LPS-treated aorta in a concentration-dependent manner. This was reduced by thiopental 0.3-1 mmol litre-1. Treatment with L-arginine 1 mmol litre-1 increased concentrations of nitrite, the end product of nitric oxide; this was not affected by thiopental 1 mmol litre-1. We conclude that thiopental suppressed cGMP formation in iNOS-induced vascular smooth muscle without affecting nitric oxide production.

Anesthetics, Intravenous↗

Mechanisms of isoflurane-increased submaximum Ca2+-activated force in rabbit skinned femoral arterial strips.

BACKGROUND: Isoflurane enhances contraction in isolated intact arterial rings by a protein kinase C (PKC) activator and also causes contracture in skinned arterial strips. This study investigated the mechanisms of this isoflurane activation of the contractile proteins of skinned strips. METHODS: The skinned strips, mounted on photodiode force transducers, were prepared from rabbit femoral arteries treated with saponin. The strips were activated by 1 microM Ca2+ (buffered with 7 mM EGTA) with or without inhibitors for PKC and calmodulin-dependent protein kinase II (CaM kinase II). When force reached steady state, isoflurane was administered and changes in force were observed. Another group of the strips was frozen to assay myosin light chain phosphorylation (MLC-p) using two-dimensional electrophoresis and immunoblotting. Analysis of variance was used to compare the results from test and control groups. Probability values <0.05 were significant. RESULTS: Isoflurane (1-5%) dose dependently increased (24-81%) the Ca2+-activated force. At 1% and 5% isoflurane, MLC-p did not change either as the force increased or reached a new steady state level. However, with 3% isoflurane, MLC-p transiently decreased (29.1% and 17.1% of total MLC for 0% and 3% isoflurane, respectively). The 3% isoflurane-increased force was blocked by 10 microM bisindolymaleidmide, an inhibitor of PKC, but not by 10 microM Gö-6976, an inhibitor of Ca2+-dependent PKC, and was enhanced 50% by 0.1 mM KN-62, an inhibitor of CaM kinase II. CONCLUSIONS: Isoflurane increased submaximum Ca2+-activated force in skinned femoral arterial strips by activating Ca2+-independent PKC, possibly epsilon isoezyme. The isoflurane-decreased MLC-p may be caused by activation of CaM kinase II.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Genetic alterations of mixed hyperplastic adenomatous polyps in the colon and rectum.

Some mixed hyperplastic adenomatous polyps (MHAPs) contain dysplastic lesions or even carcinomas. These polyps are considered to be different from ordinary hyperplastic polyps and may have a preneoplastic potential. We investigated APC and K-ras mutations in MHAPs of the colon and rectum, and also in colorectal adenomas and hyperplastic polyps to identify molecular differences between MHAPs, adenomas and hyperplastic polyps, using direct sequencing of mutation cluster regions (MCR) in APC and K-ras. No APC mutations were identified in 12 MHAPs and 8 hyperplastic polyps, whereas 10 of 27 (37.0%) adenomas showed somatic mutations. K-ras mutations were identified in one of 12 (8.3%) MHAPs, one of 8 (12.5%) hyperplastic polyps, and 10 of 27 (37.0%) adenomas. p53 mutation was found in a carcinoma arising in an MHAP. Mutations other than APC mutations may play a role in the development of MHAPs.

Adenoma↗

Neuroradiological characteristics of ecchordosis physaliphora. Case report and review of the literature.

An extremely rare case of ecchordosis physaliphora is presented in which the authors focus especially on its radiological characteristics. The patient complained of a headache with no other neurological abnormalities. A thorough radiological examination revealed a small intradural prepontine mass with no bone destruction of the clivus. Magnetic resonance imaging was very useful in visualizing this mass as a low signal intensity lesion on T1-weighted images and as a high signal intensity lesion on T2-weighted images without any contrast enhancing effects. At surgery, a cystic gelatinous nodule was found ventral to the pons; the nodule was connected to the dorsal wall of the clivus via a delicate stalk. Histological studies proved that this was an ecchordosis physaliphora. Review of the literature demonstrates that the reported cases of ecchordoses have many common radiological features that would suggest the diagnosis of this rare disease.

Brain↗

Use of the QRS scoring system in the early estimation of myocardial infarct size following reperfusion.

While the QRS scoring system has been established as a convenient tool for estimating infarct size in nonreperfused patients during the chronic stage of myocardial infarction, its applicability to reperfused patients in the acute stage has not been established. To investigate whether infarct size could be estimated by the QRS scoring system soon after reperfusion, we evaluated QRS scores obtained serially 6 hours to 1 month after reperfusion, total creatine kinase release, and left ventricular ejection fraction in 126 patients with acute myocardial infarction who underwent successful reperfusion therapy. A significant correlation was observed between the QRS score obtained after 6 hours and that obtained after 1 month (r = .89). The QRS scores obtained after 6 hours and 1 month were significantly correlated with total creatine kinase release (r = -.65 and r = -.75, respectively) and left ventricular ejection fraction (r = .62 and r = .76, respectively). Thus, the QRS scoring system can be used as a simple and economical method for estimation of infarct size soon after reperfusion.

Aged↗

A case of cor triatriatum in an eighty-year-old man: transesophageal echocardiographic observation of multiple defects.

An 80-year-old man was admitted to the hospital because of recurrent syncope caused by sick sinus syndrome. Conventional transthoracic echocardiography showed a membranelike echo-dense structure across the left atrium. Subsequently we confirmed the diagnosis of cor triatriatum with multiple defects and shunt flows across the membrane by transesophageal color flow Doppler echocardiography. There were no other associated congenital anomalies. The patient recovered well and was discharged from the hospital after implantation of a permanent VVI pacemaker for sinus node dysfunction. No other cardiac intervention for the cor triatriatum was done except follow-up with echocardiography. About 1 year after discharge, he died of massive cerebral infarction. The cardiac autopsy findings were compatible with the transesophageal echocardiogram. This is a rare case of uncorrected cor triatriatum in an elderly patient.

Aged↗

Inverted repeats in the TATA-less promoter of the rat catalase gene.

The rat catalase gene promoter lacks a TATA box, and has eight initiation sites of transcription as well as several GT and CCAAT boxes. To elucidate the mechanism of transcription in this TATA-less promoter, we analyzed nuclear factors binding to this regulatory region of the catalase gene. Functional analysis of the promoter region revealed that a pair of inverted repeat motifs located on both sides of the transcription initiation sites played an important role in the gene expression. The core sequence of this element is GYCMGGCCCKCTCYKG (M=A/C, K=G/T, Y=T/C), and four species of complex were observed to bind to this sequence. Furthermore, this element in the chimeric promoter negatively interacted with the initiator element of the terminal deoxynucleotidyl transferase gene. These results suggested that the rat catalase gene is regulated by a novel mechanism involving the inverted repeated structure of the promoter and characteristic binding factors.

Animals↗

Gas exchange function through the mastoid mucosa in ears after surgery.

Gas exchange function through the mastoid mucosa was investigated in ears after surgery using nitrous oxide. Increase in the mastoid pressure was assessed by a micropressure sensor placed in the mastoid cavity during the second-stage revision operation performed under general anesthesia using 67% nitrous oxide, 33% oxygen, and sevoflurane on 14 ears with chronic adhesive otitis media or cholesteatoma as well as on seven ears without inflammation as controls. All seven control ears showed pressure increase in the mastoid in various degrees. In the 14 postoperative ears, nine of the 10 ears on which the mastoid mucosa had previously been able to be preserved in various degrees showed pressure increase in the mastoid, but none of the remaining four ears, which had previously had mastoidectomy, showed any pressure increase. The presence or absence of the mastoid pressure increase of those ears was also found to be correlated well with the presence or absence of mastoid aeration on computed tomography examined just before the second-stage operation. These results appear to indicate that, in ears after surgery, recovery of both the gas exchange function and aeration in the mastoid is expected only when the mastoid mucosa can be preserved even partially.

Adolescent↗

Serum levels of cardiac troponin I and troponin T in estimating myocardial infarct size soon after reperfusion.

BACKGROUND: Cardiac troponin I (TnI) and troponin T (TnT) are highly specific myocardial markers. OBJECTIVE: To determine whether their serum levels can be used to estimate myocardial infarct size soon after reperfusion. METHODS: We measured the serum levels of TnI, TnT, and creatine kinase every 3 h, and the serum cardiac myosin light chain I (MLCI) every 24 h, in 42 patients with acute myocardial infarction in whom reperfusion therapy had successfully been performed. We calculated the severity of regional hypokinesis by analyzing the follow-up ventriculograms with the centerline method. RESULTS: The time from reperfusion to the peak level for TnI was 6.1 +/- 3.5 h, significantly shorter than those for creatine kinase (7.5 +/- 4.1 h) and MLCI (55 +/- 28 h). The time to peak level for TnT (6.8 +/- 4.0 h) differed significantly from that for MLCI but not from that for creatine kinase. There was a significant correlation between the peak levels of TnI and TnT (r = 0.86). The peak TnI and TnT levels were correlated well to the peak creatine kinase level (r = 0.67 and 0.69, respectively), total creatine kinase release (r = 0.66 and 0.66), and the peak MLCI level (r = 0.71 and 0.80). We observed excellent correlations between the peak levels of TnI and TnT, and regional hypokinesis (r = -0.84 and -0.85, respectively). These were comparable to the correlations between regional hypokinesis and the peak creatine kinase level (r = 0.75), total creatine kinase release (r = -0.72), and the peak MLCI level (r = -0.76). CONCLUSIONS: These results suggest that the peak serum levels of TnI and TnT in patients with successful reperfusion are accurate and early indices of infarct size.

Angioplasty, Balloon, Coronary↗

Suppression of acetylcholine-induced relaxation by local anesthetics and vascular NO-cyclic GMP system.

BACKGROUND: Local anesthetics have been demonstrated to attenuate acetylcholine-induced relaxation of vascular smooth muscle, but the mechanism responsible has not been elucidated. The present study was undertaken to ascertain whether this effect of local anesthetics is due to suppression of the vascular nitric oxide (NO)-cyclic GMP (cGMP) system. METHODS: Isolated rat aortae were cut into helical strips and mounted in bathing solution to measure isometric tension changes. They were precontracted with phenylephrine (0.3 microM) then exposed to cumulative concentrations of relaxants including acetylcholine, sodium nitroprusside (SNP) and papaverine, in the absence or presence of local anesthetics. Aortae for cGMP measurements were cut longitudinally into pairs of strips and bathed in the solution without tension. In the absence or presence of anesthetics, they were stimulated with acetylcholine or SNP, and the cGMP content of each strip was radioimmunoassayed. RESULTS: Acetylcholine-induced, endothelium-dependent relaxation of phenylephrine-precontracted aortae was attenuated by lidocaine (30-300 microM), tetracaine (10-30 microM), bupivacaine (10-100 microM) and ropivacaine (30-100 microM). SNP-induced relaxation was attenuated by lidocaine (300 microM), tetracaine (30 microM), bupivacaine (10-100 microM) and ropivacaine (30-100 microM). Papaverine-induced relaxation was attenuated by lidocaine (300 microM), bupivacaine (30-100 microM) and ropivacaine (30-100 microM), and augmented by tetracaine (30 microM). Cyclic GMP levels in acetylcholine-stimulated aortae were reduced significantly by lidocaine (300 microM), tetracaine (100 microM) and bupivacaine (300 microM) treatment, but not by ropivacaine (300 microM). SNP-stimulated cGMP levels were reduced by tetracaine (100 microM) but not by any other anesthetics at the concentrations tested. CONCLUSION: We conclude that lidocaine, tetracaine and bupivacaine suppress acetylcholine-stimulated formation of cGMP. However, the attenuation of acetylcholine-induced relaxation by local anesthetics is not totally ascribable to reduced cGMP levels.

Acetylcholine↗

[Urease-negative Helicobacter pylori isolates from gastrointestinal mucosa of patients with peptic ulcer].

It is well known that Helicobacter pylori produced a large amount of urease which plays an important role in the maintenance of infection and adhesion. Two thousand three hundred and thirty-one specimens of the gastrointestinal mucosa were obtained from patients with peptic ulcer to isolate H. pylori strains. Of these specimens, 1602 strains of H. pylori were isolated and 7 urease-negative H. pylori strains were found. Biological characteristics (except urease production) of urease-negative H. pylori were in accord with urease-positive reference strains (ATCC strains). Furthermore, these urease-negative strains were confirmed to be H. pylori strains by PCR. These results suggest that the emergence of urease-negative strains pose a new problem for H. pylori infection in patients with peptic ulcer.

Gastric Mucosa↗

[Living related liver transplantation for patients with ornithine transcarbamylase deficiency].

Ornithine transcarbamylase deficiency (OTCD) is an inborn error of urea synthesis inherited as an X-linked trait, a clinical manifestation of which is a repeated episodes of hyperammonemic coma. Recently, liver transplantations have been performed in these patients in the USA and Europe. We experienced the anesthetic managements of liver transplantations in two OTCD patients, who had been suffering from several episodes of hyperammonemic decompensation despite a restricted protein diet with administration of sodium benzoate. Anesthesia was induced and maintained with a combination of fentanyl and midazolam in both cases. Their postoperative courses were good without any neurological damages, though one patient had hyperammonemic attack during the operation.

Amino Acid Metabolism, Inborn Errors↗

[Mitrofanoff procedure with bladder-sparing urethrectomy in female urethral carcinoma: report of a case].

A 60-year-old woman with urethral carcinoma treated by bladder sparing surgery is reported. A tumor of Grabstald's clinical stage C2 arose from the anterior urethra infiltrated into the distal wall of vagina with invasion of vaginal mucosa. Pathological findings revealed poorly differentiated squamous cell carcinoma. She underwent a wide local excision of the urethra and the anterior vaginal wall with preserving the bladder. An appendicovesicostomy (Mitrofanoff procedure was selected for the urinary diversion. This technique provided a small stoma, appropriate continence, normal bladder sensation and preseving renal function. Bladder-sparing urethrectomy could be an alternative treatment for female urethral tumors.

Appendix↗

Right ventricular stiffness measured by a new method without volume estimation in coronary artery disease.

This study was designed to measure the right ventricular (RV) stiffness (delta P/ delta V) with a new method without estimating the RV volume itself. RV stiffness has rarely been measured due to the difficulty in estimating the RV volume. Without measuring RV volume itself, stiffness can be determined by measuring its volume change (delta V). Tricuspid filling flow volume, which is the diastolic RV delta V, is measurable by using Doppler echocardiography. Thus, RV stiffness may possibly be obtained from Doppler echocardiography combined with high-fidelity RV pressure. Subjects consisted of 8 controls, 8 patients with angina pectoris, 8 with anterior, 8 with posterior, and 8 with inferior prior myocardial infarction. Tricuspid annular dimension was measured by 2-dimensional echocardiography and the tricuspid annular area was calculated. Velocity-time integral of the tricuspid filling flow during the late diastole was measured by pulsed Doppler echocardiography. Then, the late diastolic RV delta V was obtained as the product of the tricuspid annular area and the integral. The late diastolic RV pressure rise (delta P) was also measured with a micromanometer catheter. The RV elastic chamber stiffness constant ([delta P/ delta V]/P) was obtained by dividing simple stiffness by the mean RV pressure during late diastole. The RV elastic chamber stiffness constant did not significantly differ among controls, patients with angina pectoris, and those with anterior and posterior myocardial infarction (0.0054 +/- 0.0009 vs 0.0057 +/- 0.0018 vs 0.0064 +/- 0.002 vs 0.0052 +/- 0.0019 ml-1). However, it was significantly increased in patients with inferior myocardial infarction (0.010 +/- 0.004 ml-1, p < 0.01 or 0.05) compared with those in the other 4 groups. These results suggest (1) that RV stiffness can be measured with a new method without RV volume estimation, and (2) that this new method is useful in evaluating RV diastolic pathophysiology in patients with coronary artery disease.

Aged↗

Corticobasal degeneration: widespread argentophilic threads and glia in addition to neurofibrillary tangles. Similarities of cytoskeletal abnormalities in corticobasal degeneration and progressive supranuclear palsy.

A 57-year-old man had exhibited cortical sensory disturbance, rigidity, spasticity, dementia, alien hand, grasp reflex, supranuclear ophthalmoplegia, pseudobulbar palsy, and neck dystonia for 4 years. Histological examination of autopsied specimens revealed neuronal loss in the cerebral cortex, with ballooned neurons, subthalamic nucleus, substantia nigra, basal ganglia, midbrain tegmentum, and the thalamus. There were neurofibrillary tangles in the subthalamic nucleus and the substantia nigra. Gallyas-Braak silver impregnation demonstrated numerous argentophilic tangles, threads, and a few argentophilic glia in the cerebral cortex, subcortical white matter, particularly in the precentral gyrus, subcortical nuclei, and the brainstem. These argentophilic structures were largely positive for tau, and negative for ubiquitin, paired helical filaments, and phosphorylated neurofilament. Ultrastructurally, 15-nm-wide straight tubules were observed in the neurons of the substantia nigra, globus pallidus, and the precentral cortex, coexisting with a few twisted tubules periodically constricted at 160- to 230-nm intervals. It was conclusively shown that Gallyas- and tau-positive cytoskeletal abnormalities occurred widely in brain of corticobasal degeneration. Both distribution and morphology of abnormal phosphorylated tau protein in corticobasal degeneration appear to resemble these features in progressive supranuclear palsy. These findings suggest a common cytoskeletal etiopathological significance in corticobasal degeneration and progressive supranuclear palsy.

Basal Ganglia↗