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Biomedical subjects

D Saito

Publications and source records attributed to D Saito.

At least 73 records · Page 4Linked to original sources

Early afterdepolarization abolished by potassium channel opener in a patient with idiopathic long QT syndrome.

We describe a 17-year-old boy with idiopathic long QT syndrome and repeated syncopal episodes. Early afterdepolarization (EAD) in the monophasic action potential (MAP) was demonstrated in the posterior septum of the left ventricle. Injection of the potassium channel opener nicorandil decreased EAD and shortened MAP duration. The syncopal episodes due to ventricular fibrillation disappeared after administration of the potassium channel opener.

Action Potentials↗

[Detection of K-ras mutation from malignant cells in sputum with mutant-allele specific amplification (MASA) method].

Sputum cells from 44 lung cancer patients (22 adenocarcinoma, 19 squamous cell carcinoma and 3 small cell carcinoma cases) were examined to contain mutant K-ras genes. The mutant-allele-specific amplification (MASA) method was used for detection of K-ras point mutations. The reaction was designed to amplify only mutant codons with polymerase chain reaction (PCR). Codons 12, 13 and 61 were studied with synthesized primers. Two cases (primary adenocarcinoma of the lung and pancreas adenocarcinoma with lung metastasis) were positive for point mutations at codon 12. The mutation of GGT to GTT was found in the first case and to GAT in the second one. Further experiments with colony hybridization revealed the mutations were found in 1% of alleles in both cases. There were no point mutations found at codon 13 nor 61. Our experiments showed it is possible to detect K-ras mutation in sputum cells from lung cancer patients, with MASA method.

Adenocarcinoma↗

Clinical trial of continuous infusion of 5-fluorouracil using an ambulatory pump for metastatic colorectal cancer.

A clinical trial was conducted in order to evaluate the anti-tumor effect and toxicity of a continuous infusion of 5-fluorouracil (5-FU) for metastatic colorectal cancer. Two-hundred and fifty mg/m2/day 5-FU was administered as a continuous infusion through an indwelling central venous catheter with ambulatory pump. Twenty patients with metastatic colorectal cancer which could be measured or evaluated were enrolled in the trial. The objective response rate was 35% (95% confidence interval, 14-56%). The response rates by site were 33% in liver, 17% in lung, 60% in lymph nodes, 50% in adrenal gland and 50% in primary lesion. The major toxicity was stomatitis (50%; grades 2 and 3 on Eastern Cooperative Oncology Group (ECOG) criteria) and hand-foot syndrome (40%; grades 2 and 3 on ECOG criteria). The sequence of toxicity was stomatitis first, followed by hand-foot syndrome. The median cumulative dose of 5-FU from the initiation of therapy to the onset of toxicity was 7125 mg in stomatitis and 17,875 mg in hand-foot syndrome. These toxicities were mild and reversible after a short interruption to the 5-FU infusion. Neither hematological toxicity nor serious catheter-related complications were observed. We concluded that continuous infusion of 5-FU was a feasible treatment for the patient with metastatic colorectal cancer, and manageable on an out-patient basis.

Adult↗

Small depressed cancer of the large bowel: report of three cases.

This report describes three patients in whom colonoscopy detected small depressed cancers (without an elevated component) that had invaded the submucosa. They represent 0.4% (3/884) of all patients with invasive cancers and 3% (3/101) of patients with submucosal cancers in the National Cancer Center Hospital between January 1990 and February 1994. This type of cancer may have been overlooked in the past because of its small, flat nature. A slight deformity of the lumen, a faint color change (slightly reddish), and a loss of a vascular network pattern were important colonoscopic findings. Small depressed cancers may follow a different pathway to advanced cancer than polypoid cancers, although both pathways are included in the adenoma-carcinoma sequence. We should be aware of these lesions in our efforts to detect colorectal cancers in the early stage.

Adenocarcinoma↗

[The evaluation of systolic right ventricular pressure and right ventricular hypertrophy using body surface mapping (isointegral map, isochrone map)].

We studied QRS and QRST isointegral maps, and isochrone map for the diagnosis of right ventricular hypertrophy and its severity in atrial septal defects and primary pulmonary hypertensions. The discriminant analysis in QRS isointegral map showed better results for differential diagnosis between atrial septal defects and both normal subjects and incomplete right bundle branch block patients than these in QRST isointegral map and isochrone map. Three parameters (Qp/Qs, systolic right ventricular pressure, right ventricular ejection fraction) for right ventricular overload showed significant correlation with QRS isointegral map and QRS isopotential map. Thus body surface map was an useful method for the evaluation of right ventricular hypertrophy.

Body Surface Potential Mapping↗

Detection of novel mutations in the gyrA gene of Staphylococcus aureus by nonradioisotopic single-strand conformation polymorphism analysis and direct DNA sequencing.

A total of 36 clinical isolates of Staphylococcus aureus (29 fluoroquinolone-resistant strains and 7 fluoroquinolone-susceptible strains) were studied for the presence of point mutations in the gyrA gene by nonradioisotopic single-strand conformation polymorphism (Non-RI SSCP) analysis with silver stain. Direct DNA sequencing analysis of the PCR-amplified DNA fragments confirmed the results obtained by Non-RI SSCP analysis and revealed that fluoroquinolone resistance is closely associated with six types of mutations in the gyrA gene, of which three types of mutations were newly identified: (i) Ser-84-->Leu and Glu-88-->Gly, (ii) Ser-84-->Leu and Glu-88-->Lys, and (iii) Glu-88-->Gly. Furthermore, the novel ATT-->ATC mutation at codon 86 (silent mutation) was seen in only one fluoroquinolone-susceptible strain. All seven mutational types were separated from the wild type in a single electrophoretic step within 3 h after PCR amplification. Thus, we conclude that this new technique is a rapid, simple, and useful screening method for the genotyping of gyrA mutations associated with fluoroquinolone resistance.

Base Sequence↗

Role of endothelium-derived nitric oxide and adenosine in functional myocardial hyperemia.

To investigate the role of endothelium-derived nitric oxide (EDNO) and adenosine in functional myocardial hyperemia, we examined the effect of NG-nitro-L-arginine (L-NNA) and 8-p-sulfophenyltheophylline (8-SPT) on coronary vasodilation in response to increased myocardial oxygen consumption in pentobarbital sodium-anesthetized dogs. L-NNA significantly attenuated the increase in coronary conductance from 28 +/- 6 to 16 +/- 2% with atrial pacing, from 69 +/- 5 to 36 +/- 6% with isoproterenol, and from 25 +/- 6 to 9 +/- 4% with constriction of the aorta. 8-SPT given alone attenuated the increase in coronary conductance to the same extent as L-NNA. The combined administration of L-NNA and 8-SPT did not further change coronary conductance. These findings suggest that EDNO and adenosine play an important role in functional hyperemia. EDNO-induced functional hyperemia appears to be dependent on adenosine receptor activation.

Adenosine↗

Effects of nipradilol on venous hemodynamics: evaluation with a Doppler blood flow method.

Nipradilol is a newly synthesized beta-blocker which has a propranolol-like structure and contains a nitrate moiety. To examine the effect of nipradilol on venous blood flow, a single oral dose of nipradilol (6 mg) and propranolol (20 mg) was administered in the same 15 normal volunteers on separate days. Peak flow velocities, flow velocity integrals, and the diameter of the right brachiocephalic vein were measured before and 2 h after drug administration using Doppler echocardiography. These two beta-blockers significantly decreased systolic blood pressure to the same extent as they did heart rate. Nipradilol dilated the venous diameter by 8% and decreased peak flow velocity by 8% during systole and 9% during diastole. The flow velocity integral in one cardiac cycle also decreased significantly by 14%. Propranolol, however, failed to modify these parameters. These results suggest that nipradilol decreased venous return through its nitroglycerin-like direct vasodilating action.

Adult↗

"Very well differentiated tubular adenocarcinoma" of the stomach: its endoscopic and histopathological characteristics.

Between 1986 and 1991, 31 patients having tubular adenocarcinoma with low cellular and structural atypism ("very well differentiated tubular adenocarcinoma:" tub 0) underwent surgery at the National Cancer Center Hospital (NCCH). Histologically, the 31 lesions in the 31 patients were very similar to those observed in gastric adenoma (World Health Organization) with severe atypism. Their malignancy could be diagnosed only on the basis of cellular atypism, i.e., uneven distribution of chromatin in the nucleus accompanied by irregularity in the size or shape of the spindle-form nucleus, abnormal nuclear polarity and/or obvious nucleoli. Histologically, the border between the tub 0 and adenomatous areas ('front line' of carcinoma) could not be identified within the neoplastic lesion, which showed relatively regularly shaped tubuli (less structural atypism). Of the 31 cases, 30 were solitary early gastric cancer (EGC). Their clinicopathological features were compared with those of 34 cases of gastric adenoma, 237 cases of solitary well differentiated (tub 1) and 127 cases of moderately differentiated (tub 2) tubular adenocarcinoma which had been resected at the NCCH during the same period. Most (75%) of the 30 tub 0 EGCs were type IIc (depressed) macroscopically, despite their histological similarity to gastric adenoma which showed a high (90%) elevated appearance incidence. The incidence of small lesions, < 2 cm in diameter, was highest in gastric adenoma (82%), followed by tub 0 (64%), although the tub 0 lesions showed a wide range of sizes. Small lesions were less frequent in the tub 1 (43%) and tub 2 (33%) cases. The incidence of submucosal invasion was significantly lower in tub 0 cases (17%) than in tub 1 (39%) and tub 2 (46%) cases (P < 0.05). No lymph node metastasis was seen in tub 0 cases, but was seen in 6.4% and 9.4% of tub 1 and tub 2 cases, respectively. With regard to the endoscopic appearance of depressed mucosal cancer, the incidence of encroachment (moth-eaten appearance) on the tips of folds was significantly lower (10%) and the appearance of marginal elevation was significantly higher (79%) in tub 0 than in tub 1 (each P < 0.05) or tub 2 (each P < 0.01). The results suggest that 'tub 0' can be regarded as a less malignant but not benign tumor, and that its endoscopic characteristics provide valuable information which can be used to ensure that patients receive suitable treatment.

Adenocarcinoma↗

Morphometric analysis of colorectal dysplasia with image processing.

Nuclear and structural abnormalities on the histological specimens of colorectal dysplasias were quantified by using 10 parameters. From the measured values, the following histological findings were obtained: progression from mild to severe dysplasia was associated with an increase in nuclear size, and nuclear arrangement became more irregular. There was, however, no difference between the nuclear size and arrangement in severe dysplasia and those in carcinoma. The nuclei were spindle shaped in mild and moderate dysplasia. On the other hand, they were relatively round in severe dysplasia and carcinoma. Structural abnormalities tended to increase with the histological abnormalities. These results correspond well with the histological abnormalities by which the pathologists grade dysplasia and diagnose carcinoma subjectively. Therefore, these 10 parameters might be useful for quantifying histological characteristics of colorectal dysplasias.

Cell Nucleus↗

Effect of running training on uncoupling protein mRNA expression in rat brown adipose tissue.

The effect was investigated of endurance training on the expression of uncoupling protein (UCP) mRNA in brown adipose tissue (BAT) of rats. The exercised rats were trained on a rodent treadmill for 5 days per week and a total of 9 weeks. After the training programme, a marked decrease in BAT mass was found in terms of weight or weight per unit body weight; there was a corresponding decrease in DNA content and a downward trend in RNA and glycogen levels. The UCP mRNA was present at a markedly decreased level in BAT of trained animals. In consideration of the reduced levels of mRNAs for hormone-sensitive lipase and acyl-CoA synthetase, the brown adipose tissue investigated appeared to be in a relatively atrophied and thermogenically quiescent state.

Adipose Tissue, Brown↗

Morning increase in hemodynamic response to exercise in patients with angina pectoris.

The present study was conducted to determine whether or not there is diurnal variation in the hemodynamic responses to stimuli that increase myocardial oxygen demand, and the effects of such variation on electrocardiograms (ECG). Fifteen patients with angina pectoris, 17 patients with old myocardial infarction, and 8 healthy controls were examined in this study. Graded exercise stress testing was conducted in the supine position, once in the morning and once in the afternoon, using a bicycle ergometer. A standard 12-lead ECG was recorded before, immediately after, and 3, 5, and 10 min after the end of the exercise. The exercise ECG and blood pressure changes were compared among the groups and, within each group, the results after morning and afternoon exercise were compared. Hemodynamic responses, including heart rate, blood pressure, and the pressure-rate product, showed greater increases in the morning than in the afternoon in angina patients and controls, in association with greater depression of the electrocardiographic ST-segment. In contrast, patients with old myocardial infarction exhibited no difference in hemodynamic responses or the ST-pattern from morning to afternoon. The results suggest that diurnal variation of hemodynamic responses to increased oxygen demand may explain, at least partly, why myocardial ischemia of effort angina is more severe in the morning than in the afternoon.

Adult↗

Effects of oral theophylline on sick sinus syndrome.

OBJECTIVES: We sought to determine the effect of theophylline on cardiac pauses in sick sinus syndrome. BACKGROUND: Sick sinus syndrome, a relatively benign condition, is usually treated with pacemaker implantation without any proved effectiveness. Thus, an appropriate pharmacologic therapy would be useful. METHODS: Theophylline (200 to 400 mg/day for 1 month) was initially administered orally to 17 patients with sick sinus syndrome, which is manifested by sinus pauses of > 2.5 s. Eleven of the 17 patients subsequently received theophylline for an additional 8 to 37 months. Twenty-four-hour Holter recordings were obtained before treatment, at the end of 1 month of treatment and then at 6-month intervals. RESULTS: Theophylline decreased the frequency of sinus pauses from 256 +/- 230 to 23 +/- 62 pauses per 24 h and decreased the duration of the longest pauses from 4.7 +/- 1.8 to 2.2 +/- 0.97 s after 1 month of treatment. Subjective symptoms associated with cardiac pauses disappeared in 16 of 17 patients. Ventricular premature beats increased in frequency but did not last longer than two beats. Three patients experienced adverse effects. Nine of the 11 patients receiving long-term treatment had a good outcome, but 2 patients required a pacemaker because of the reappearance of long sinus pauses. CONCLUSIONS: The results suggest that oral theophylline may be beneficial for the treatment of patients with sick sinus syndrome.

Administration, Oral↗

Rapid diagnosis of gastric malignant lymphoma from biopsy specimens: detection of immunoglobulin heavy chain rearrangement by polymerase chain reaction.

The endoscopic appearances of the gastrointestinal lymphomas differ widely, and it is often difficult to make the distinction between a benign lymphoproliferative disorder and a malignant lymphoma even with a histologic evaluation. Since almost all primary malignant lymphomas of the gastrointestinal tract are of B-cell origin, the confirmation of monoclonality in immunoglobulin (Ig) is helpful for differential diagnosis. Rearrangements of the Ig heavy chain gene were examined by polymerase chain reaction (PCR) analysis in frozen biopsy specimens of human stomach. The sensitivity of the analysis was sufficient to detect even a 5% clonal B-cell proliferation and results could be obtained within 17 h. In a clinical investigation, seven of eight cases (88%) of primary gastric malignant lymphoma showed a single band in polyacrylamide gel electrophoresis (PAGE) after PCR, suggesting a monoclonal proliferation of B-cell lineage. By contrast, all seven cases of reactive lymphoreticular hyperplasias showed a broad smear pattern in PAGE, which is thought to reflect polyclonal proliferation. None of the lymphocytes infiltrating around gastritis (7 cases), gastric ulcers (12 cases) and gastric carcinomas (15 cases) showed a monoclonal proliferation pattern. These findings suggest that detection of monoclonality in Ig heavy gene rearrangement by PCR is useful for the differential diagnosis of B-cell lymphoproliferative diseases in the gastrointestinal tract.

Base Sequence↗

Helicobacter pylori may be transmitted through gastrofiberscope even after manual Hyamine washing.

Endoscopy is an effective diagnostic technique for gastric cancer, which is believed to be associated with Helicobacter pylori. Manual Hyamine washing is a widely used fiberscope cleaning method. Urease B gene of Helicobacter pylori was detected in 50% of the wash-out samples from the biopsy-suction channel of a fiberscope after manual Hyamine washing by nested polymerase chain reaction, and bacterial culture revealed viable Helicobacter pylori in 19%. However, Helicobacter pylori was not detected by either of the above methods in the biopsy-suction channel of the fiberscope after mechanical washing. These findings indicate that manual Hyamine washing of fiberscopes is insufficient to prevent iatrogenic Helicobacter pylori transmission, and that mechanical washing after manual Hyamine washing is essential.

Base Sequence↗

Relationship between pressure-rate product and myocardial oxygen consumption of normal and hypertrophic right ventricles in open-chest dogs.

There are few reports on the relationship between right ventricular performance and its myocardial oxygen consumption (RVMVO2). The present study was conducted to investigate the relationship between RVMVO2 and the mechanical performance of normal and hypertrophic right ventricles in open-chest dogs. Right ventricular hypertrophy (RVH) was induced by producing chronic right ventricular pressure overload by banding the pulmonary arteries of 8 puppies for 6 months. The experiment was performed under basal conditions and after increasing the RVMVO2 in the eight dogs with RVH as well as in 20 normal dogs. The RVMVO2 showed significant positive relationships with right coronary (RCA) flow, right ventricular systolic pressure, and right ventricular pressure-rate product (PRP) in both the normal right ventricle and RVH hearts. However, the slope between the PRP and RVMVO2 was significantly steeper in the normal right ventricle (RV) than in the hypertrophic RV. When the PRP was normalized for the thickness of the right ventricular free wall, the slope of the two regression lines merged into a single line of fit. These results suggest that the pressure-rate product can be used to predict myocardial oxygen demand not only in the normal RV but also in well-compensated, hypertrophic RV. Isoproterenol induced smaller increases in cardiac output in the dogs with RVH than in those with normal RV. It also appears that the cardiac output of the hypertrophic RV is less sensitive to beta-adrenoceptor stimulation than that of the normal RV.

Animals↗

Intravenous injection of adenosine triphosphate for assessing sinus node dysfunction in patients with sick sinus syndrome.

The clinical value of rapid intravenous injection of adenosine triphosphate (ATP, Adephos Kowa # L3, CAS 56-65-5) for assessing sinus node function was examined in 5 patients with sick sinus syndrome (SSS) and 6 normal controls. All patients with SSS showed cardiac pauses longer than 3 s on a 24-h Holter ECG monitoring. First, after prophylactic insertion of a temporary pacemaker in the right ventricle, overdrive suppression test was conducted using the standard technique, and sinus node recovery time (SNRT) was observed to evaluate the sinus node function. Then, 10 min later, 10 mg of ATP was rapidly injected intravenously, and body surface and intracavitary ECG were continuously recorded until the basal state was regained. The rapid injection of ATP resulted in a slight inhibition of sinus node automaticity in normal subjects, but marked inhibition was in patients with SSS associated with suppression of AV conduction. The longest post ATP atrial cycle (AA interval in the intracavitary ECG showed a close inverse relationship with SNRT corrected for basal sinus length (CSNRT), according to the following formula: longest AA interval (ms) = 3.32 x CSRT (ms) +254.4 (r = 0.91, p < 0.001). The results suggest that rapid intravenous injection is a useful tool for the diagnosis of SSS.

Adenosine Triphosphate↗

Effects of inosine on adenosine-induced coronary vasodilation in the open chest dog.

The effects of inosine (CAS 58-63-9) on adenosine-induced coronary vasodilation were studied in open-chest dogs. Inosine and hypoxanthine were infused into the coronary artery at a rate to obtain respective calculated coronary plasma concentrations of 10(-5) mol/l, and the dose-coronary flow response of adenosine was recorded with and without inosine or hypoxanthine infusion. When the maximum coronary dilation was obtained, 10 ml of 2 x 10(-3) mol/l 8-phenyltheophylline (8-PT) solution was injected into the femoral vein. Additionally, adenosine deaminase activity was measured in vitro in the presence of various concentrations of either inosine or hypoxanthine. It was found that inosine, but not hypoxanthine, intensified the coronary vasodilatory effect of adenosine, which was abolished by 8-PT injection: EC50 of adenosine was reduced from 10(-5.43) mol/l to 10(-5.90) mol/l by inosine. Inosine and hypoxanthine did not affect adenosine deaminase activity at concentrations of 10(-4) mol/l or less. These findings indicate that inosine intensifies the coronary vasoactivity of adenosine, independent of inhibition of adenosine deaminase activity.

Adenosine↗