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Biomedical subjects

T Ishikawa

Publications and source records attributed to T Ishikawa.

At least 163 records · Page 9Linked to original sources

Effect of a low-fat diet enriched with oleic acid on postprandial lipemia in patients with type 2 diabetes mellitus.

The aim of the present study was to compare the effects of a low-fat diet enriched with oleic acid to those of a low-fat diet enriched with linoleic acid on fasting lipids, postprandial lipemia, and oxidative susceptibility of low-density lipoprotein (LDL) in patients with type 2 diabetes mellitus (DM). In a 3-wk randomized crossover study, eight patients with type 2 DM were given an experimental low-fat diet enriched with either oleic acid or linoleic acid. The oleic-acid-enriched diet contained 5, 15, and 5%, energy from saturated, monounsaturated, and polyunsaturated fatty acids, and the linoleic-acid-enriched diet contained 5, 5, and 15% energy from saturated, monounsaturated, and polyunsaturated fatty acids, respectively. In addition to evaluating the fasting lipids and oxidative susceptibility of LDL, we evaluated postprandial lipemia using an oral fat load at the end of each 3-wk dietary phase. There were no significant differences in fasting lipid profile or lag time of LDL oxidation between the two experimental dietary phases. The average and maximal increments of remnant-like particle (RLP) cholesterol levels during oral fat load were significantly higher after the oleic-acid-enriched dietary phase than after the linoleic-acid-enriched dietary phase. The area under the curve of RLP cholesterol was also significantly larger after the oleic-acid-enriched dietary phase than after the linoleic-acid-enriched dietary phase. These results suggest that the oleic-acid-enriched diet was associated with increased formation of postprandial chylomicron remnants compared with the linoleic-acid-enriched diet.

Aged↗

A new procedure for chronic atrial fibrillation: bilateral appendage-preserving maze procedure.

BACKGROUND: Atrial transport and atrial natriuretic peptide secretion is severely reduced from normal after the maze III procedure. To improve these factors, we developed a bilateral appendage-preserving maze procedure (BAP-maze). METHODS: Forty-six patients with chronic atrial fibrillation who underwent the BAP-maze procedure were compared with 40 patients who underwent the maze III procedure. The ratio of the peak velocity of the A and E waves of transmitral flow (transthoracic pulsed Doppler echocardiography), the left atrial appendage ejection fraction (transesophageal echocardiography), and the atrial natriuretic peptide secretory reserve during treadmill exercise test were measured at 6 months postoperatively. RESULTS: Sinus rhythm was restored in 44 patients (95.7%) by the BAP-maze procedure and in 39 patients (97.5%) by the maze III procedure. The ratio of the peak velocity of the A and E waves was 0.52 +/- 0.22 in the BAP-maze group and 0.25 +/- 0.19 in the maze III group (p < 0.0001). The left atrial appendage ejection fraction was 44.7% +/- 11.5%, and the atrial natriuretic peptide secretory reserve was greater in the BAP maze group (p = 0.037). CONCLUSIONS: The BAP-maze procedure improved atrial transport and atrial natriuretic peptide secretion as well as simplifying the maze operation, without decreasing its effectiveness against atrial fibrillation.

Aged↗

Risk stratification using serum concentrations of cardiac troponin T in patients with end-stage renal disease on chronic maintenance dialysis.

BACKGROUND: It has been recently suggested that cardiac troponin T (cTnT) may be more sensitive than troponin I (cTnI) for subclinical myocardial cell injury in patients on chronic dialysis. METHODS: We prospectively compared the predictive value of cTnT with cTnI, atrial (ANP) and brain natriuretic peptide (BNP) in 100 consecutive outpatients on chronic dialysis without acute coronary syndromes over a period of 3 months, and assessed whether the combination of cTnT with clinical information including age, duration of dialysis, and medical histories was useful for risk stratification of these patients. During the 2-year follow-up period, 19 patients died, mostly due to cardiac causes (53%). RESULTS: The area under the receiver operator characteristic (ROC) curve for the cTnT as predictor of both overall and cardiac death was significantly greater than the area under the cTnI curve (p < 0.0001 and p = 0.01), the BNP curve (p < 0.001 and p < 0.01) or the ANP curve (p < 0.0001 and p < 0.005). In a stepwise multivariate Cox regression analysis, only cTnT (p < 0.05 and p < 0.01) and a history of heart failure requiring hospitalization (p < 0.05 and p < 0.005) were independent predictors of both all cause and cardiac mortality. Using parameters of cTnT > or =0.1 microg/l and/or history of heart failure, the overall and cardiac mortality rate for the low risk group (n=66) were 4.5% and 1.5%, respectively, 40% and 16% for the intermediate risk group (n=25), and 67% and 56% for the high risk group (n=9). CONCLUSION: cTnT concentrations offer a higher prognostic accuracy than cTnI, ANP and BNP in patients on chronic dialysis. The combination of elevated cTnT and a history of heart failure may be a highly effective means of risk stratification of these patients.

Adult↗

Oxidized heptenes from flowers of Melodorum fruticosum.

Three oxidized heptenes, 7-benzoyloxy-6-oxo-2,4Z-heptadiene-1,4-olide, [7-benzoyloxy-4-hydroxy-1-methoxy-2E,4Z-heptadiene-1,6-dione] and 7-benzoyloxy-6-oxo-2,4E-heptadiene-1,4-olide, were isolated from flowers of Melodorum fruticosum. Their structures were determined by spectral data analysis. The first two compounds exhibited moderate cytotoxicity against a panel of human tumor cell lines, whereas the third was inactive.

Alkenes↗

Glucides of Cnidium monnieri fruit.

From the fruit of Cnidium monnieri Cusson (Umbelliferae), two glucides were isolated together with other known glucides. Their structures were clarified as glycerol 2-O-alpha-L-fucopyranoside and D-quinovitol (6-deoxy-D-glucitol), respectively.

Apiaceae↗

Beta(3)-adrenoceptor agonists for the treatment of frequent urination and urinary incontinence: 2-[4-(2-[[(1S,2R)-2-hydroxy-2-(4-hydroxyphenyl)-1-methylethyl]amino]ethyl)phenoxy]-2-methylpropionic acid.

In a search for novel analogues of beta(3)-adrenoceptor (AR) agonists relaxing the bladder for treatment of urinary dysfunction, 2-[4-(2-[[(1S,2R)-2-hydroxy-2-(4-hydroxyphenyl)-1-methylethyl]amino]ethyl)phenoxy]-2-methylpropionic acids (1a-e), into which a fibrate-like structure had been incorporated, were synthesised. Compound 1a was found to be a selective beta(3)-AR agonist in functional assays using the ferret detrusor (beta(3)-AR), rat uterus (beta(2)-AR), and rat atrium (beta(1)-AR); beta(3): EC(50)=7.8 nM, beta(2): IC(50)=7,300 nM, beta(1): EC(20)=23,000 nM. The introduction of a chlorine atom or methyl substituent at the ortho-position on the phenyl ring of 1a further improved beta(3)-AR selectivity. In an in vivo study, 1a lowered intrabladder pressure (ED(50)=31 microg/kg) in rats, without increasing heart rate, in keeping with the in vitro results. Consequently, it is proposed that 1a and its analogues (1b-e), possess beta(3)-AR agonistic activity in the absence of undesirable beta(1)- or beta(2)-AR mediated actions, and may be useful for clinical treatment and pharmacological studies.

Adrenergic beta-3 Receptor Agonists↗

Magnetic resonance imaging in hemifacial hyperplasia.

We describe a case of hemifacial hyperplasia due to a combination of lipoma and lipomatosis. The contribution of MRI to the diagnosis of hemifacial hyperplasia and to monitoring growth and development in this condition is demonstrated.

Anatomy, Cross-Sectional↗

G649, an allelic variant of the human H2 receptor with low basal activity, is resistant to upregulation upon antagonist exposure.

Orange et al reported an allelic variant of the human histamine H2 receptor, in which adenine 649 was replaced with guanine, to be more frequent in the schizophrenic population than controls in British Caucasians. The A649 to G change causes an Asn to Asp transition at amino acid position 217 in the third intracellular region, which is postulated to be important for receptor function. Herein, we analyzed the functional significance of this variant using wild-type and variant receptors expressed in Chinese hamster ovary cells. The variant receptor was associated with markedly lower basal cAMP productions than the wild-type receptor. Histamine-dependent cAMP productions via the variant receptor were lower as well. Treatment of cells expressing variant receptors with 10(-5) M ranitidine for 24 h resulted in a reduced degree of receptor upregulation as compared with the wild-type receptor. Thus, this is the first report of an allelic variant of the human H2 receptor which confers altered receptor function. To analyze gastric acid secretion in individuals with this variant, we examined 100 Japanese control subjects. However, neither heterozygotes nor homozygotes were found, suggesting that this variant, if present, is uncommon in the Japanese population.

Alleles↗

Selective enhancement of thrombopoietic activity of PEGylated interleukin 6 by a simple procedure using a reversible amino-protective reagent.

We developed a novel method for the chemical modification of cytokines with synthetic polymers to increase the therapeutic efficacy of the former in vivo. A pH-reversible amino-protective reagent, dimethylmaleic anhydride (DMMAn), was used for modification of interleukin-6 (IL-6) with polyethylene glycol (PEG). The novel PEG-conjugated IL-6 (DmPEG-IL-6), which had been pretreated with DMMAn before PEGylation, showed up to a 140% increase in in vitro specific activity compared with PEG-IL-6 that had been synthesized by the previous method. Moreover, DmPEG-IL-6 caused thrombopoiesis more potently in mice than PEG-IL-6. The DmPEG-IL-6 Fr.1, having 3-4 PEG chains attached to the cytokine, showed the strongest thrombopoietic effect among the DmPEG-IL-6s with different molecular sizes that were tested. PEG-IL-6 Fr.1 had a 500-fold higher potency in stimulating thrombopoiesis than native IL-6 and DmPEG-IL-6 Fr.1 achieved a threefold higher thrombopoietic effect than PEG-IL-6 Fr.1. In addition, side-effects, such as an increase in the plasma fibrinogen level, were not observed after injection of either PEG-IL-6s or DmPEG-IL-6s. These results suggest that PEGylation with DMMAn pretreatment may become a useful means for clinical cytokine delivery.

Animals↗

Improved survival with oral administration of enteric-coated tegafur/uracil for advanced stage IV-A hepatocellular carcinoma.

BACKGROUND AND AIMS: There is currently no proven chemotherapy regimen for hepatocellular carcinoma (HCC). The principal chemotherapeutic approach in most cases is infusion therapy into the hepatic arteries feeding the tumors. However, the clinical effects of chemotherapy are extremely poor. Therefore, in the present study, we conducted a prospective randomized trial of the efficacy of oral administration of enteric-coated tegafur/uracil for advanced HCC. METHODS: From 1994 to 1999, a total of 56 consecutive patients with unresectable stage IV-A HCC were studied prospectively to examine the efficacy of enteric-coated tegafur/uracil in HCC and to determine the significant prognostic factors. Twenty-eight patients were treated only with enteric-coated tegafur/uracil without other anticancer treatment. Another 20 patients were given conservative management only. The remaining eight patients withdrew from the study. RESULTS: In the group treated only with enteric-coated tegafur/uracil, the median survival time and 1 and 2 year survival rates were 12.13 months and 55.3 and 36.9%, respectively. In the control group, the median survival time and 1 year survival rate were 6.20 months and 5.5%, respectively. By both univariate analysis and multivariate analysis using Cox's proportional hazards model, treatment with enteric-coated tegafur/uracil was shown to be the factor most significantly favoring a better prognosis. CONCLUSIONS: Although the prognosis of most patients with stage IV-A HCC is poor, administration of enteric-coated tegafur/uracil induces long-term survival and is an effective treatment for stage IV-A HCC.

Administration, Oral↗

High viral loads, serum alanine aminotransferase and gender are predictive factors for the development of hepatocellular carcinoma from viral compensated liver cirrhosis.

BACKGROUND AND AIMS: The aims of the present study were to determine the occurrence rate of hepatocellular carcinoma (HCC) and to assess the risk factors for the development of HCC in compensated viral liver cirrhosis. METHODS: Two hundred and thirty-nine cirrhotic patients (65 hepatitis B surface antigen (HBsAg) positive, 165 hepatitis C virus (HCV) antibody positive (anti-HCV), and nine with both HBsAg and anti-HCV positivity) were studied. The Kaplan-Meier method evaluated by a log-rank test was used to estimate the cumulative probability of HCC development. Independent predictors of HCC development were estimated by using the Cox proportional hazard regression analysis. RESULTS: Dual infection manifested as HBsAg and anti-HCV positive was the highest risk of HCC. Multivariate analysis indicated that anti-HCV positive, HBsAg positive, and lactate dehydrogenase were independent predictors of the development of HCC among individuals with viral cirrhosis. In the HBsAg-positive group, a high-titer of HBV-DNA (more than 3.7 log genome equivalents (LGE)/mL) was most predictive of HCC development. In the anti-HCV-positive group, male gender and a high-titer of HCV-RNA (more than 1.0 Meq/mL) were predictive factors for the development of HCC. CONCLUSIONS: Individuals with high viral loads should be monitored for the development of HCC. Clinical efforts at eradicating or reducing the viral load may reduce the risk for HCC.

Alanine Transaminase↗

Pleomorphic adenoma of the parotid gland with extensive bone formation.

We report an unusual case of pleomorphic adenoma with extensive bone formation, occurring in the parotid gland of a 58-year-old Japanese man. The tumor was a well-circumscribed mass that measured 20 x 20 x 15 mm and contained extensive bone formation. Histologically, most of the tumor was composed of bone and chondroid tissues. The bone formation with a marrow-like structure occupied half the volume of the tumor. The chondroid tissues merged continuously into bone tissues. The bone tissue seemed to be formed within areas of chondral tissue by a process of enchondral ossification. Except for the unusual amount of large bone formation, the tumor showed histology of pleomorphic adenoma, particularly at the periphery of the tumor. These histological findings suggest the possibility of extensive enchondral ossification in pleomorphic adenoma.

Adenoma, Pleomorphic↗

Doppler index and plasma level of atrial natriuretic hormone are improved by optimizing atrioventricular delay in atrioventricular block patients with implanted DDD pacemakers.

Doppler index is the sum of isovolumetric contraction time and isovolumetric relaxation time divided by ejection time and has clinical value as an index of combined systolic and diastolic myocardial performance. This crossover study compared the Doppler index and atrial natriuretic hormone (atrial natriuretic peptide) [ANP] between optimal (AV) delay and prolonged AV delay in patients with DDD pacemakers. The study included 14 patients (6 men, 8 women, age 78.4+/-9.3 [SD] years) with AV block with an implanted DDD pacemaker. AV delay was prolonged in a 25-ms, stepwise fashion starting from 125 ms to 250 ms. Pacing rate was set at 70 beats/min. Cardiac output (CO) was assessed by pulsed Doppler echocardiography, and optimal AV delay was defined as the AV delay at which CO was maximum, and an AV delay setting of 250 ms as prolonged AV delay. Plasma level of ANP and Doppler index determined by echocardiography were measured 1 week after programming. AV delay was switched to another AV delay and measurements were repeated after 1 week. Optimal AV delay was 159+/-19 ms. Doppler index was significantly lower at optimal AV delay than at prolonged AV delay (0.68+/-0.26 vs 0.92+/-0.30, P < 0.05). The plasma ANP level was significantly lower at optimal AV delay than at prolonged AV delay (29.0+/-30.7 vs 52.6+/-44.9 pg/mL, P < 0.05). In conclusion, the Doppler index and the plasma ANP level were significantly lower at optimal AV delay than at prolonged AV delay. This study shows the importance of the optimal AV delay setting in patients with an implanted DDD pacemaker, the Doppler index and plasma ANP levels are good indicators for optimizing AV delay.

Aged↗

Optimal atrioventricular delay setting determined by evoked QT interval in patients with implanted stimulus-T-driven DDDR pacemakers.

Cardiac function is improved by optimizing the atrioventricular (AV) delay. An automatic optimizing function of AV delay may be necessary to achieve the most favourable haemodynamic state in paced patients. The QT interval may change when cardiac function is improved by optimizing the AV delay. The QT or stimulus-T interval is used as a sensor for rate-responsive pacemakers. Evoked (e) QT interval is measured as the time duration from the ventricular pace pulse (stimulus) and the T-sense point that is the steepest point of the intracardiac T wave (stimulus-T interval). The relationship between AV delay, eQT interval and cardiac function was studied in 10 patients (73 +/- 10 (SD) years old) with an implanted stimulus-T-driven DDDR pacemaker. Cardiac output (CO) and pulmonary capillary wedge pressure (PCWP) were measured by Swan-Ganz catheter. The AV delay was prolonged stepwise by 30 ms. Electrocardiogram event markers which indicated ventricular spike and sensed T wave were recorded, and the interval between two event markers was measured as eQT interval. When AV delay was changed from 240 ms to the AV delay at which CO was maximal (172 +/- 33 ms), eQT interval prolonged from 346 +/- 60 to 353 +/- 62 ms (P < 0.01). There was a significant positive correlation between the optimal AV delay at which CO was maximal (172 +/- 33 ms) and the optimal AV delay which was predicted from the maximum eQT interval (179 +/- 37 ms, r = 0.92, P < 0.001). When AV delay was changed from 240 ms to the predicted optimal AV delay, CO increased from 4.2 +/- 0.7 to 4.5 +/- 0.81.min-1 (P < 0.001) and PCWP was decreased from 7.1 +/- 4.0 to 5.7 +/- 3.1 mmHg (P < 0.05). In conclusion, the optimal AV delay can be predicted from the eQT interval which is sensed by an implanted pacemaker. Automatic setting of the optimal AV delay may be achieved by the QT sensor of an implanted pacemaker.

Aged↗

Investigation on diabetic autonomic neuropathy assessed by power spectral analysis of heart rate variability in WBN/Kob rats.

This article investigates the development of cardiovascular autonomic dysfunction caused by diabetes mellitus. We performed power spectral analysis of heart rate variability in WBN/Kob rats as a model of spontaneous diabetes. The heart rate of the rats was measured continuously for 24 hours with an implanted telemetric transmitter, and power spectral analysis of heart rate variability was performed on continuous electrocardiograms. At 4 to 5 months of age, the rats indicated a tendency toward a decrease in plasma insulin concentration without hyperglycemia. At 8 to 9 months of age, they showed remarkable hyperglycemia, loss of the circadian rhythm of the heart rate, and reversion or loss of the circadian rhythm of the blood pressure. By the power spectral analysis of heart rate variability, it became apparent that the circadian rhythm of the low frequency/high frequency ratio was absent even in prediabetic WBN/Kob rats. In addition, the circadian rhythms of the high-frequency power level and low frequency/high frequency ratio were absent in diabetic WBN/Kob rats. These findings indicate that the autonomic nervous system in WBN/Kob rats is progressively damaged from the prediabetic to diabetic state. In conclusion, diabetic autonomic neuropathy may be characterized by the appearance of sympathetic overactivity that precedes the impairment of parasympathetic activity.

Animals↗

Impaired glucose tolerance without hypertriglyceridemia does not enhance postprandial lipemia.

Postprandial lipemia has been thought to be one of risk factors for coronary heart disease, and enhances in potential patients for atherosclerotic disease. Patients with impaired glucose tolerance (IGT) often show hypertriglyceride, which is caused by enhanced portprandial lipemia. Therefore, postprandial lipemia in patients with IGT and without hypertriglyceridemia has not been cleared. We have examined the levels of plasma triglyceride and chylomicron remnants after a high fat meal load (1250 kcal, 40% fat and 420 mg cholesterol) in 13 normotriglyceridemic subjects with IGT and 10 controls with normal glucose tolerance (NGT). Chylomicron remnants were evaluated as remnant-like particles (RLP) that were not bound to an immunoaffinity gel mixture containing apo A-I and apo B-100 monoclonal antibody. RLP cholesterol levels 4 hours after the fat load were significantly lower in IGT subjects than in NGT subjects. Increase of RLP cholesterol after the fat meal load only significantly correlated with increase of insulin during the first 30 min after a 75 g oral glucose tolerance test, but not fasting lipid, insulinogenic index and HOMA-R (homeostasis model) in all subjects. These results suggest that postprandial response does not enhance in IGT subjects, and may associate with early-phase insulin secretion and without insulin resistance in normotriglyceridemic men with IGT or NGT.

Antibodies, Monoclonal↗

Thoracoscopic thermal ablation therapy for hepatocellular carcinoma located beneath the diaphragm.

BACKGROUND AND STUDY AIMS: Percutaneous interstitial thermal ablation therapy effectively treats hepatocellular carcinoma (HCC) that can be visualized on percutaneous ultrasonography. However, when the tumor is located just under the top of the diaphragm, visualization can be difficult with conventional ultrasonographic examination. There are also problems concerning complete tumor ablation. We performed thoracoscopic thermal ablation therapy for HCC located just beneath the diaphragm in nine patients with advanced liver cirrhosis. PATIENTS AND METHODS: Eight patients underwent thoracoscopic microwave coagulation therapy, and one patient underwent thoracoscopic radiofrequency ablation therapy. RESULTS: Despite the poor hepatic reserve, postoperative recovery after thoracoscopic thermal ablation therapy was rapid in all patients, without deterioration of hepatic function. CONCLUSIONS: This preliminary study suggests that the new technique of thoracoscopic thermal ablation therapy is a less invasive optional therapy for HCC located in segments VII or VIII in cirrhotic patients.

Aged↗