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Biomedical subjects

T Sakata

Publications and source records attributed to T Sakata.

At least 55 records · Page 3Linked to original sources
PubMed2001

Lack of noninvasive markers of ventricular repolarization inhomogeneity in patients with idiopathic ventricular tachyarrhythmia.

Noninvasive markers reflecting repolarization inhomogeneity have been proposed to be useful indices for identifying patients at risk of ventricular arrhythmias based on organic heart disease. In this study, we clarify whether or not repolarization inhomogeneity markers are useful in patients with idiopathic ventricular tachycardia (VT). We investigated T-wave alternans (TWA) and corrected QT-interval dispersion (QTD) in 84 consecutive patients with idiopathic VT, 90 patients with VT associated with organic heart disease (organic VT), and 87 normal individuals. VT was defined as tachycardia lasting > or =5 consecutive ventricular ectopic beats at a rate of > or =120 beats/min. TWA was positive in 20 of 84 patients (24%) with idiopathic VT, 59 of 90 patients (66%) with organic VT, and 16 of 87 normal individuals (18%). The alternans voltage was 2.6 +/- 3.1 micro V in idiopathic VT patients, 5.6 +/- 6.4 micro V in organic VT patients, and 2.9 +/- 5.7 micro V in normal individuals. QTD were 53 +/- 20 ms in idiopathic VT patients, 92 +/- 20 ms in organic VT patients, 46 +/- 18 ms in normal individuals, respectively. A positive TWA test result was seen more (P <.01) frequently, and QTD was longer (P <.01) in organic VT patients compared to normal individuals, whereas there was no difference between idiopathic VT patients and normal individuals. In addition, in patients with idiopathic VT, neither did any of these measurements differ between patients with sustained VT (lasting for > or =30 s) and those with nonsustained VT. Noninvasive markers of repolarization inhomogeneity, such as TWA and QTD, are not useful for identifying patients with idiopathic VT. Repolarization inhomogeneity may not affect to the pathogenesis of idiopathic VT.

Adult↗
PubMed2001

A nested variant of transitional cell carcinoma of the urinary bladder: a case report.

Nested variants of transitional cell carcinomas (TCC-NVs) are relatively rare neoplasms in the urinary bladder, but at least 25 cases have been described. This disease is characterized by the pathological finding of irregular nests and/or tubules of transitional carcinoma cells infiltrating the lamina propria without involvement of the mucosal layer. In our case, diagnosed by open biopsy, there were scattered tumor cells observed from the muscle layer to the subserosa, with a tendency toward increasing cellular anaplasia with the depth of invasion. Since the prognosis of TCC-NV is generally poor, comprehensive chemotherapy was performed. No changes were observed on computed tomography and the performance status (0) remained the same after 1 year, so the treatment was considered effective. We conclude that open biopsy should be carried out without hesitation when bladder cancer is suspected, even if there are negative findings of repeated urinary cytology examination and/or endoscopic cold cup biopsy. Immunohistochemical analysis may help in the diagnosis of TCC-NVs derived from epithelial cells. Diagnosis and treatment at an early stage should reduce the mortality of patients with TCC-NVs.

Aged↗
PubMed2001

Predicting the recurrence of ventricular tachyarrhythmias from T-wave alternans assessed on antiarrhythmic pharmacotherapy: a prospective study in patients with dilated cardiomyopathy.

BACKGROUND: Microvolt T-wave alternans (TWA) has been proposed as a useful index to identify patients at risk of ventricular tachyarrhythmias. Recent studies have demonstrated that antiarrhythmic drugs, such as amiodarone and procainamide, decrease the prevalence of TWA. In this study, we tested whether TWA in patients on antiarrhythmic pharmacotherapy significantly predicts the recurrence of ventricular tachyarrhythmias in patients with dilated cardiomyopathy. METHODS: To evaluate the ability to predict the recurrence of ventricular tachyarrhythmias, determinate TWA and left ventricular ejection fraction (LVEF) were prospectively assessed in 49 patients with ischemic or nonischemic dilated cardiomyopathy on antiarrhythmic pharmacotherapy for sustained ventricular tachycardia (VT) or ventricular fibrillation (VF). The pharmacotherapy consisted of class I (17 patients), III (29 patients), and IV (3 patients) antiarrhythmic drugs. The study endpoint was the first recurrence of sustained VT or VF on treatment during the follow-up period. RESULTS: TWA was positive on antiarrhythmic pharmacotherapy in 30 patients (61%). During a follow-up of 13 +/- 11 months, the sustained VT or VF recurred in 21 of the 41 patients (51%) with available follow-up data. The sensitivity of TWA and LVEF for predicting recurrence of ventricular tachyarrhythmias was 76 and 38%, specificity was 60 and 70%, positive predictive value was 67 and 57%, and negative predictive value was 71 and 52%. Kaplan-Meier event-free analysis revealed that TWA was a significant risk stratifier (P = 0.02), whereas LVEF was not. CONCLUSIONS: This prospective study suggests that TWA significantly predicts the recurrence of ventricular tachyarrhythmias, even on antiarrhythmic pharmacotherapy, in patients with dilated cardiomyopathy. TWA may also be a useful marker for evaluating the efficacy of antiarrhythmic drugs for ventricular tachyarrhythmias.

Adult↗
PubMed2001

Asymptomatic inflammatory bowel disease with special reference to ulcerative colitis in apparently healthy persons.

OBJECTIVE: We examined cases of asymptomatic inflammatory bowel diseases, particularly asymptomatic ulcerative colitis, which were found in apparently healthy Japanese persons who underwent general health screening. METHODS: Patients with positive immunological fecal occult blood test (IFOBT) among approximately 236,000 persons participating in the health screening program at the Aichi Prefectural Center for Health Care for the past 9 yr underwent total colonoscopy. In patients with ulcerative colitis, we investigated the sex and age distributions, extent of lesion, endoscopic activity, incidence rate, and clinical course. RESULTS: In all, 35 cases of inflammatory bowel disease were detected, and 274 cases of colorectal cancer (not discussed here) were detected in the same population. The 35 cases of inflammatory bowel disease consisted of 19 cases of ulcerative colitis (12 of asymptomatic and minimally symptomatic ulcerative colitis, and seven of symptomatic or with past history of ulcerative colitis); five of intestinal tuberculosis; two of Crohn's disease; two of amebic colitis; and seven of endoscopic colitis. The 12 patients with asymptomatic and minimally symptomatic ulcerative colitis consisted of 11 men and one woman aged 36-63 yr (mean 46.2 yr). We classified these cases into three grades of severity according to endoscopic findings: four cases were mild, eight moderate, and none severe. Of these 12 cases, three were found endoscopically because of positive IFOBT, although barium enema was normal. Anatomic types of colitis cases included three of total colitis, three left-sided colitis, two proctitis, and four right-sided or segmental colitis. In one case, the disease extended proximally during the course of observation. CONCLUSIONS: We found 35 cases of inflammatory bowel disease because of positive IFOBT performed as part of a general health screening. Of these, 19 cases were ulcerative colitis. These included many asymptomatic and minimally symptomatic cases, which could be very important in helping to elucidate the natural history of ulcerative colitis; thus, long-term follow up is necessary.

Adult↗
PubMed2001

Development of a new method for assessing the cardiac baroreflex: response to downward tilting in patients with diabetes mellitus.

OBJECTIVE: To investigate the clinical value of a new non-invasive method for assessing baroreflex sensitivity using downward tilting. PATIENTS: 34 patients with diabetes mellitus, mean (SD) age, 53.6 (11.8) years. DESIGN: Arterial blood pressure and ECG were recorded simultaneously while the patients were on a tilt table. After 20 minutes at a 70 degrees upright tilt, the patients were returned to the supine position at a speed of 3.2 degrees /s (downward tilting baroreflex sensitivity test, DT-BRS). A beat to beat systolic blood pressure increase associated with a corresponding lengthening of the RR interval was noted during downward tilting. Baroreflex sensitivity was also assessed using the conventional method of an intravenous injection of phenylephrine (Phe-BRS). Heart rate variability was analysed during rest and tilting. RESULTS: The slope of the regression line for systolic blood pressure v RR interval during downward tilting was highly correlated with Phe-BRS (r = 0.83, p < 0.0001). Both DT-BRS and Phe-BRS were correlated with the high frequency (HF) component of resting heart rate variability (p < 0.005) and with the ratio of the low frequency to the high frequency component (LF/HF) during upright tilting (p < 0.005). DT-BRS and Phe-BRS were also correlated with the difference between rest and tilting values of HF and LF/HF (p < 0.005). CONCLUSIONS: DT-BRS provides a physiological, non-invasive method for determining baroreflex sensitivity and may be a useful index of reflex cardiac vagal and sympathetic function in patients with diabetes mellitus.

Adult↗
PubMed2001

VLCD-induced weight loss improves heart rate variability in moderately obese Japanese.

To evaluate the effects of weight reduction on the autonomic nervous system in obese patients, we investigated heart rate variability (HRV) based on 24-hr ambulatory electrocardiogram (ECG) recordings before and after weight reduction. To aim for weight reduction, 16 obese patients were treated with the very-low-calorie conventional Japanese diet (VLCD-CJ) therapy combined with behavior therapy. Percent weight reduction was 17.8% +/- 1.5% (means +/- SEM), but mean blood pressure did not change significantly after VLCD-CJ therapy. The mean normal R-R interval (mNN) of the 24-hr ECG and all other five time-domain indices increased after weight reduction. Spectral analysis revealed that weight reduction increased the high frequency (HF) component, but decreased the ratio of low to high (LF/HF) components. Rate of change in mNN or HF correlated positively with reduction rate of body mass index, but not that in LF/HF. Analysis of daily fluctuations in each HRV parameter showed that significant improvement after weight loss occurred mainly during the nocturnal period, but an HF component was improved throughout the day and night periods. These findings indicate that functional impairment of the autonomic nervous system in obese subjects, particularly in the nocturnal period, is improved by effective weight reduction after VLCD-CJ therapy.

Adult↗
PubMed2001

Orexin-A regulates body temperature in coordination with arousal status.

Orexins, hypothalamic neuropeptides, are involved in modulation of food intake and arousal status. To further examine their physiological roles in brain function, the effect of centrally administered orexin-A on body temperature was investigated in rats. Assessed by a telemetry sensor system implanted into the abdominal cavity, infusion of orexin-A into the third cerebroventricle (i3vt) increased body temperature in a dose-responsive manner. Expression of uncoupling protein 1 (UCP1) mRNA in brown adipose tissue (BAT), as a marker for peripheral thermogenesis, failed to increase after the infusion. Expression of UCP3 mRNA in skeletal muscle was up-regulated, whereas UCP2 in white adipose tissue was unchanged after the infusion. The resulting information indicates that orexin neurons regulate body temperature in coordination with arousal status independently of peripheral thermogenesis, which is regulated by BAT UCP1.

Adipose Tissue↗
PubMed2001

Transplantation of normal islets into the portal vein of Otsuka Long Evans Tokushima Fatty rats prevents diabetic progression.

To investigate the long-term effects of normal pancreatic islet transplantation on progression of obese type 2 diabetes mellitus (DM), 1500 normal islets (per rat) from Wistar King A rats at 8 weeks of age were transplanted into the liver through the portal vein of Otsuka Long Evans Tokushima Fatty (OLETF) rats, an animal model of obese type 2 DM, at 12 weeks of age. Body weight in the transplanted OLETF (IT) rats 8 and 28 weeks after islet transplantation did not differ from that in the corresponding sham-operated (SO) rats, but was greater than that in lean littermates (LETO rats; P < 0.05 for each group). In the early phase, 8 weeks after transplantation, rats in both IT and SO groups were normoglycemic, but hyperinsulinemic (P < 0.05 for each compared with LETO rats), probably resulting from increased body weight. In the late phase, 28 weeks after transplantation, hyperglycemia in the IT group was greatly attenuated compared with the SO group (P < 0.05), but hyperinsulinemia remained in both the IT and the SO groups compared with that in the LETO group (P < 0.05 for each). Immunohistochemical studies demonstrated that hypertrophic and fibrotic changes in pancreatic islets, together with mesangial proliferation of the glomerular matrix, an indicator for diabetic nephropathy, were attenuated predominantly in the IT group at the late phase after transplantation compared with those in the corresponding phase of the SO group. Islet transplantation into the liver of OLETF rats thus prevented further progression of obese type 2 DM. A possible mechanism is that islet transplantation may prevent development of hyperglycemia by improving abnormal hepatic glucose metabolism and consequently insulin resistance, which may lead to blockade of a vicious cycle between advancing damage to pancreatic islet cells and increased demand for insulin secretion, thus sparing original pancreatic cells from exhaustion induced by increased demand for insulin secretion.

Animals↗
PubMed2001

Clinical usefulness of the combination of T-wave alternans and late potentials for identifying high-risk patients with moderately or severely impaired left ventricular function.

Ventricular tachyarrhythmia (VT) is an independent risk factor for an increased overall mortality in patients with impaired left ventricular (LV) function, but there is not an established noninvasive tool to detect such patients. The present study aimed to clarify the most useful noninvasive approach for identification of patients with moderately or severely impaired LV function complicated by VT. Sixty-seven patients in New York Heart Association (NYHA) classes I-III with an LV ejection fraction (LVEF) less than 40% and an LV end-diastolic dimension (LVDD) of at least 55 mm on echocardiography were enrolled. Impaired LV function was caused by either ischemic (n=30) or nonischemic dilated cardiomyopathy (n=37). T-wave alternans (TWA), QT dispersion (QTD), and late potentials (LP) on signal-averaged electrocardiography were sequentially determined without using antiarrhythmic drugs. VT was defined as more than 6 consecutive ventricular ectopic beats. The mean NYHA class was 1.9+/-0.7, mean LVEF was 31+/-8%, and mean LVDD was 65+/-10mm. A history of VT was present in 26 of the patients (39%). Univariate and multivariate logistic analysis showed that TWA and LP were closely related to VT, whereas NYHA> or =III, LVEF<30%, LVDD> or =70mm, and QTD> or =90ms were not. The combination of TWA and LP had the most significant value (p=0.0004, odds ratio=8.44) by univariate analysis, and only this combination had significant value in multivariate analysis (p=0.04). Therefore, the combination of TWA and LP could be a useful index for identifying those patients with impaired LV function who are at risk for VT.

Action Potentials↗
PubMed2001

[Monoaminergic anorectic agents].

Catecholamine, dopamine, serotonine (5HT) and neuronal histamine are anorectic monoamines and act as anorectic neurotransmitters. The anorectic agents as modulators of these monoamines inhibit appetite by activating release together with suppressing reuptake of those monoamines. The anorectic agents were classified in clinical use into either alpha 1, beta-adrenergic receptor agonists or 5HT-receptor agonist. Dexfenfluramine, a 5HT-receptor agonist, was inhibited in clinical use because of its cardiac complications including pulmonary hypertension and valvelar disease. Mazindol is an adrenergic agonist and the solitary anti-obesity drug used clinically in Japan. Sibutramine shows the effects of both beta-adrenergic and serotonergic receptor agonists. Sibutramine induces not only appetite suppression but also acceleration of peripheral energy expenditure. No histaminergic anorectics have been employed in the clinical situation to date. L-Histizine, precursor amino acid of endogenous neuronal histamine, is useful for suppression of food intake, lipolytic acceleration of peripheral adipose tissues and enhanced energy expenditure in both animals and humans. L-Histizine thus inspires development of more effective and safer anorectics that can be used without suffering from the rebound phenomenon of body weight.

Adrenergic Agents↗
PubMed2001

[Leptin-induced regulation of fat metabolism and its accumulation].

Recent findings have shown that supplementation of leptin decreases body weight in leptin-deficient ob/ob mice through its suppressive effect on food intake and accelerating effect on energy expenditure, particularly on peripheral fat lipolysis. When endogenously hyperleptinemic obese rats were further induced to be hyperleptinemic exogeously using adenovirus vector, their body fat mass was reduced but not food intake. These findings implicate a direct lipolytic action of leptin on peripheral adipose tissues in obese rats because leptin transport capacity across the blood-brain barrier is almost saturated by the relative hyperleptinemia. Recovery from excessive body fat accumulation after adenovirus-induced hyperleptinemia is much slower than that after caloric restriction because there may be difference between those treatments in decreased lipogenic enzymes activities and/or increased activities of fatty acid oxidative enzymes and thermogenic uncoupling proteins. The fat melting effects of leptin may show its crucial pharmacologic potencies to design therapeutic strategies against morbid obesity. The studies on leptin provide a better understanding for creative approaches to anti-obesity drug that are efficient for reducing body fat mass without harmful side-effects.

Animals↗
PubMed2001

Structural elucidation and synthesis of 3-hydroxybenzene-1,2-dicarbaldehyde from astigmatid mites.

The structure of a novel aromatic compound contained in the unidentified Rhizoglyhus mite (Acaridae: Astigmata) was elucidated, without its isolation, to be 3-hydroxybenzene-1,2-dicarbaldehyde (tentatively named gamma-acaridial) by a combination of GC/MS and GC/FT-IR together with knowledge of related mite compounds. The structure was confirmed by a 5-step synthesis, starting from methyl 3-hydroxybenzoate, in a 15% overall yield. The compound is widely distributed not only among Astigmata but also among Oribatida, although its biological function is obscure at present.

Aldehydes↗
PubMed2001

Structural elucidation of twelve novel esters composed of five fatty acids and three new branched alcohols together with four monoterpenoids from Sancassania shanghaiensis (Acari: Acaridae).

A total of 12 novel esters and four monoterpenoids (rosefuran, (2R,3R)-epoxyneral, and alpha- and beta-acaridials) were detected by GC/MS analyses as the opisthonotal gland components of Sancassania shanghaiensis. The acidic fraction after hydrolysis was composed of five common fatty acids (palmitic, stearic, oleic, linoleic and arachidic acid), while the alcoholic fraction consisted of two major components (C6 and C8 alcohols with branched methyls), together with a trace amount of C9 alcohol. The two major alcohols were identified as new alcohols [(S)-2-methylpentanol and (2S,4S)-2,4-dimethylhexanol] by comparing the physico-chemical data of their 3,5-dinitrobenzoates with those of regio-selectively synthesized alcohols. The C9 alcohol was suggested as (2S,4S)-2,4-dimethylheptanol, based on a structural and biogenetic analogy to the C6 and C8 alcohols. Five of the compounds were each identified by GC to be (S)-2-methylpentyl esters from five fatty acids, and the other five components likewise as (2S,4S)-2,4-dimethylhexyl esters. The remaining two were suggested as (2S,4S)-2,4-dimethylheptyl stearate and linolate.

Alcohols↗
PubMed2001

Comparison of T-wave alternans and QT interval dispersion to predict ventricular tachyarrhythmia in patients with dilated cardiomyopathy and without antiarrhythmic drugs: a prospective study.

Microvolt T-wave alternans (TWA) and QT interval dispersion (QTD), which reflect temporal and spatial repolarization abnormalities, respectively, have been proposed as useful indices to identify patients at risk for ventricular tachyarrhythmias (VTs). The purpose of this study was to clarify which repolarization abnormality marker is more useful in predicting arrhythmic events in patients with dilated cardiomyopathy (DCM). Forty-two consecutive nonischemic DCM patients underwent the assessment of TWA and QTD. Patients undergoing antiarrhythmic pharmacotherapy, except beta-blockers and those with irregular basic rhythms, were excluded from entry. Eight patients were also excluded because of indeterminate test results. Therefore, 34 DCM patients were prospectively assessed. The end point of the study was the documentation of VT defined as > or = 5 consecutive ectopic beats during the follow-up period. TWA and QTD (> or = 65 msec) were positive in 24 (80%) and 11 (37%) of 30 patients with available follow-up data, respectively. There was no relationship between TWA and QTD. During a follow-up of 13+/-11 months, VTs occurred in 13 patients (43%). In Cox regression analysis, TWA was a significant risk stratifier (p=0.02), whereas QTD was not. The sensitivity, specificity, and positive and negative predictive values of TWA in predicting VTs were 100%, 35%, 54%, and 100%, respectively. TWA could be a useful noninvasive index to identify patients at risk for VTs in the setting of DCM. This study may suggest that temporal repolarization abnormality is associated more with arrhythmogenesis than with spatial repolarization abnormality in DCM patients.

Adult↗
PubMed2001

The effect of propafenone on premature ventricular contractions (PVC): an analysis based on heart rate dependency of PVCs.

The effect of 450 mg/day propafenone for two weeks on premature ventricular contractions (PVCs) was studied in combination with an assessment of heart rate (HR) dependency of PVCs using Holter ECG monitoring in patients with more than 720 PVCs per day. The PVC-HR correlation was classified into positive (P), bidirectional (B), and flat and negative (FN) correlation groups. The positive group included only patients in whom PVC frequency increased with a heart rate increase, while the bidirectional group included patients with PVCs whose frequency increased at low heart rates and decreased at high heart rates. The FN group contained both flat (PVC frequency was almost fixed regardless of heart rate changes) and negative (PVC frequency decreased as heart rate increased) correlations. The effectiveness of propafenone was 70% in the positive group and 50% in the nonpositive group which included both bidirectional (67%) and FN (0%) groups, using a > 70% PVC reduction as a criterion of efficacy. From this, we concluded that propafenone is effective in patients showing either positive or bidirectional PVC-HR correlation. The coupling interval (CI) of PVCs was also prolonged by propafenone as a whole. The present study suggests that there are differences in the mechanism of PVC development in patients with flat or negative correlation and those with a positive or bidirectional correlation. Thus, this type of analysis contributes to an understanding of the action of antiarrhythmic agents, and may allow the prediction of their efficacy on PVCs.

Aged↗
PubMed2001

Central infusion of histamine reduces fat accumulation and upregulates UCP family in leptin-resistant obese mice.

Leptin resistance has recently been confirmed not only in animal obese models but in human obesity. Evidence is rapidly emerging that suggests that activation of histamine signaling in the hypothalamus may have substantial anti-obesity and antidiabetic actions, particularly in leptin-resistant states. To address this issue, effects of central, chronic treatment with histamine on food intake, adiposity, and energy expenditure were examined using leptin-resistant obese and diabetic mice. Infusion of histamine (0.05 pmol x g body wt(-1) x day(-1)) into the lateral cerebroventricle (i.c.v.) for 7 successive days reduced food intake and body weight significantly in both diet-induced obesity (DIO) and db/db mice. Histamine treatment reduced body fat weight, ob gene expression, and serum leptin concentration more in the model mice than in pair-fed controls. The suppressive effect on fat deposition was significant in visceral fat but not in subcutaneous fat. Serum concentrations of glucose and/or insulin were reduced, and tests for glucose and insulin tolerance showed improvement of insulin sensitivity in those mice treated with histamine compared with pair-fed controls. On the other hand, gene expression of uncoupling protein (UCP)-1 in brown adipose tissue and UCP-3 expression in white adipose tissue were upregulated more in mice with i.c.v. histamine infusion than in the pair-fed controls. These upregulating effects of histamine were attenuated by targeted disruption of the H1-receptor in DIO and db/db mice. Sustained i.c.v. treatment with histamine thus makes it possible to partially restore the distorted energy intake and expenditure in leptin-resistant mice. Together, i.c.v. treatment with histamine contributes to improvement of energy balance even in leptin-resistant DIO and db/db mice.

Adipose Tissue↗
PubMed2001

Targeted disruption of histamine H1-receptor attenuates regulatory effects of leptin on feeding, adiposity, and UCP family in mice.

Histamine neurons are widely distributed in the brain and suppress food intake through the histamine H1 receptor (H1-R) in the hypothalamus. To examine the role of neuronal histamine in leptin signaling pathways, we investigated the effects of H1-R knockout (H1KO) mice on both food intake and mRNA expressions of uncoupling proteins (UCPs) as regulated by leptin, and concomitantly on basal changes in both expression of hypothalamic neuropeptides and diet-induced fat deposition in adipose tissues. H1KO mice showed no change in daily food intake, growth curve, body weight, or adiposity. Reflecting no specificity in these parameters, H1KO mice induced no basal changes in mRNA expression of hypothalamic neuropeptides, ob gene, or peripheral UCPs. Loading H1KO mice with a high-fat diet accelerated fat deposition and ob gene expression compared with the controls. Leptin-induced feeding suppression was partially attenuated in H1KO mice, indicating involvement of histamine neurons in feeding regulation as a downstream signal of leptin. Upregulation of fat UCP mRNA and reduction of body fat induced by central infusion of leptin were attenuated in the H1KO mice. These results show that H1KO mice are a novel leptin-resistant model and that H1-R is a key receptor for downstream signaling of leptin in the brain that contributes to regulation of feeding, fat deposition, and UCP mRNA expression.

Adipose Tissue↗