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Biomedical subjects

T Kawada

Publications and source records attributed to T Kawada.

At least 145 records · Page 8Linked to original sources

Closed-loop identification of carotid sinus baroreflex open-loop transfer characteristics in rabbits.

In the circulatory system, a change in blood pressure operates through the baroreflex to alter sympathetic efferent nerve activity, which in turn affects blood pressure. Existence of this closed feedback loop makes it difficult to identify the baroreflex open-loop transfer characteristics by means of conventional frequency domain approaches. Although several investigators have demonstrated the advantages of the time domain approach using parametric models such as the autoregressive moving average model, specification of the model structure critically affects their results. Thus we investigated the applicability of a nonparametric closed-loop identification technique to the carotid sinus baroreflex system by using an exogenous perturbation according to a binary white-noise sequence. To validate the identification method, we compared the transfer functions estimated by the closed-loop identification with those estimated by open-loop identification. The transfer functions determined by the two identification methods did not differ statistically in their fitted parameters. We conclude that exogenous perturbation to the baroreflex system enables us to estimate the open-loop baroreflex transfer characteristics under closed-loop conditions.

Animals↗

Vagal stimulation decreases left ventricular contractility mainly through negative chronotropic effect.

Although an increase in vagal tone is known to slow heart rate (HR), whether it also depresses left ventricular contractility through mechanisms independent of the bradycardic effect remains unknown. The chief aim of this investigation, therefore, was the separation of the observed vagally mediated depression of ventricular contractility into direct and indirect vagal effects, the latter resulting via negative chronotropism. In 12 anesthetized, sympathectomized open-chest rabbits, we measured left ventricular contractility through determination of the end-systolic elastance (Ees). We found that tonic vagal stimulation administered at 0, 5, and 10 Hz decreased both HR (226.9 +/- 39.7, 201.9 +/- 25.7, and 171.3 +/- 18.5 beats/min, respectively; P = 0.0003) and Ees (109.5 +/- 25.7, 85.1 +/- 34.1, and 71.9 +/- 33.1 mmHg/ml, respectively; P = 5 x 10(-6)) in a frequency-dependent fashion. However, we observed that as long as HR was kept constant through fixed-rate atrial pacing, vagal stimulation resulted in little or no change in Ees. Thus we conclude that the negative inotropic effect of vagal stimulation is attributable primarily to its negative chronotropic effect when sympathetic tone is minimal.

Animals↗

Interstitial norepinephrine level by cardiac microdialysis correlates with ventricular contractility.

Although a cardiac microdialysis technique has made it possible to estimate myocardial interstitial norepinephrine (NE) levels, whether such levels reflect the local NE concentration that would regulate ventricular contractility remains unknown. If such levels indicate locally regulating NE concentration, then ventricular contractility should be a unique function of the interstitial NE level regardless of how the latter is altered. To examine this hypothesis, we altered the interstitial NE level endogenously by stimulating the cardiac sympathetic nerves at 1 and 2 Hz while monitoring ventricular contractility. We also altered the interstitial NE level exogenously by means of intravenous NE infusions at 10 and 40 micrograms.kg-1.h-1. The basal NE levels did not differ between the stimulation and the infusion experiments (42.9 +/- 11.2 vs. 40.1 +/- 6.2 pg/ml, means +/- SE). The slopes of regression lines relating ventricular contractility and interstitial NE level were also not different between the two experiments [1.13 +/- 0.20 vs. 1.17 +/- 0.20%/(pg/ml), means +/- SE]. We conclude that the interstitial NE level estimated by cardiac microdialysis reflects the local NE concentration regulating ventricular contractility.

Animals↗

Increase in swimming endurance capacity of mice by capsaicin-induced adrenal catecholamine secretion.

Increase in endurance swimming capacity caused by capsaicin (CAP), a pungent component of red pepper, -induced increase of fat metabolism in mice was investigated using an adjustable-current water pool. The mice administered CAP via a stomach tube, showed longer swimming time until exhaustion than the control group of mice, in a dose-dependent manner. The maximal effect was observed at a dose of 10 mg/kg while more than 15 mg/kg had no effect. The increase of endurance was observed only when CAP was administered two hours before swimming. After the administration of CAP, the serum glucose concentration rapidly increased and then decreased within 60 min, while the concentration of serum-free fatty acids gradually increased through 3 hours. The residual glycogen concentration of the gastrocnemius muscle after 30 min of swimming was significantly higher in the CAP-administered mice than in control mice, suggesting that use of the serum free fatty acids spared muscle glycogen consumption. The serum adrenaline concentration significantly increased with twin peaks at 30 min and two hours after administration of CAP. An experiment using adrenalectomized mice was done to confirm that the effect of CAP is due to increased energy metabolism through the secretion of adrenaline from the adrenal gland. The swimming endurance capacity of the adrenalectomized mice was not increased by CAP administration, although adrenaline injection induced a 58% increase in the endurance time. These results suggest that the increase of swimming endurance induced by CAP in mice is caused by an increase in fatty acid utilization due to CAP-induced adrenal catecholamine secretion.

Animals↗

[Prognostic factors of cervical carcinoma treated with postoperative radiotherapy].

We analyzed 119 patients with cervical carcinoma treated by postoperative radiotherapy from 1983 to 1993. Five- and 10-year survival rates of all patients were 77% and 67%, respectively. The 10-year survival rates for stage I (54 patients) and stage II (65 patients) were 76% and 58%, respectively. Ten-year survival rate for patients with both deep stromal invasion and lymph node metastasis was 37% which was much lower than in those without them (more than 90 %), indicating that they seemed to be factors related to poor prognosis. The results of multivariate analysis showed that the number of metastatic lymph nodes was the most important prognostic factor. Leg edema and intestinal and urinary insufficiency as late complications of postoperative radiotherapy occurred at low incidences and were well tolerated.

Adult↗

A new technique for transurethral resection of bladder tumors: rotational tumor resection using a new arched electrode.

PURPOSE: A new technique of transurethral resection of bladder tumors is described. MATERIALS AND METHODS: A 2.5 cm. papillary, sessile bladder tumor was treated via a rotational resection technique with a new arched electrode to replace longitudinal resection using a conventional loop electrode. RESULTS: This method was easy to perform and allowed for en bloc resection of bladder tumor. CONCLUSIONS: This rotational resection technique is useful for evaluation of pathological depth of tumors in resected specimens.

Aged↗

Estimation of arterial mechanical properties from aortic and tonometric arterial pressure waveforms.

Although arterial mechanical properties have been evaluated using arterial input impedance, the relative difficulty in accurate flow measurement made the value of impedance somewhat limited. To develop an alternative method to evaluate arterial mechanical properties, we analyzed the aortic pressure (AoP)-radial arterial pressure (RAP) relationship because of relative ease in obtaining peripheral pressure waveform by tonometry. In 8 patients we simultaneously recorded aortic root and radial arterial pressure waveforms. We calculated the transfer function from AoP to RAP. We then fitted the transfer function to a model of a lossless uniform elastic tube terminated with a modified Windkessel model. The fact that the model transfer function predicted AoP from RAP waveform with considerable accuracy indicated that the model represented the arterial mechanical properties well. We conclude that we can estimate the arterial mechanical properties by the pressure-pressure transfer function analysis.

Adolescent↗

Elevation of either axoplasmic norepinephrine or sodium level induced release of norepinephrine from cardiac sympathetic nerve terminals.

Using dialysis technique, prominent accumulation of norepinephrine (NE) in the myocardial interstitial space was observed under two different conditions: (1) local administration of a monoamine oxidase inhibitor (pargyline, 1, 10 mM), (2) local administration of a Na, K-ATPase inhibitor (ouabain, 10, 100 microM). Further, pretreatment with a vesicle uptake inhibitor (reserpine, 10 microM) augmented these responses. Either condition independently caused endogenous NE release and a brisk increase in dialysate NE levels might occur as a consequence of non-exocytotic release of NE.

Animals↗

Expression of uncoupling protein in skeletal muscle and white fat of obese mice treated with thermogenic beta 3-adrenergic agonist.

The mitochondrial uncoupling protein (UCP) is usually expressed only in brown adipose tissue (BAT) and a key molecule for metabolic thermogenesis. The effects of a highly selective beta 3-adrenergic agonist, CL316,243 (CL), on UCP expression in skeletal muscle and adipose tissues were examined in mice. Daily injection of CL (0.1 mg/kg, sc) to obese yellow KK mice for two weeks caused a significant reduction of body weight, associated with a marked decrease of white fat pad weight and hypertrophy of the interscapular BAT with a sixfold increase in UCP content. Clear signals of UCP protein and mRNA were detected by Western and Northern blot analyses in inguinal, mesenteric and retroperitoneal white fat pads, and also in gastrocnemius and quadriceps muscles, whereas no signal in saline-treated mice. The presence of UCP mRNA in muscle tissues was also confirmed by reverse transcription-PCR analysis. Weaker UCP signals were also detected in control C57BL mice treated with CL, but only in inguinal and retroperitoneal fat pads. Immunohistochemical examinations revealed that UCP stains in the white fat pads were localized on multilocular cells quite similar to typical brown adipocyte, and those in the muscle tissues on myocytes. The mitochondrial localization of UCP in myocytes was confirmed by immunoelectron microscopy. In addition to UCP protein, UCP mRNA was also detected in myocytes by in situ hybridization analysis. Thus, chronic stimulation of the beta 3-adrenergic receptor induces ectopic expression of UCP in adipose tissues conventionally considered as white fat and even in skeletal muscle, which probably contributes to the potent anti-obesity effect of the beta 3-adrenergic agonist.

Adipose Tissue↗

Continuous monitoring of short-latency somatosensory evoked potentials during cardiac and aortic surgery.

The effectiveness of monitoring somatosensory evoked potentials (SEPs) intraoperatively to detect brain damage early remains controversial. To assess the diagnostic accuracy of this modality, a study was conducted between 1991 and 1994, recording SEPs in 287 consecutive patients undergoing cardiac and aortic surgery using cardiopulmonary bypass (CPB) with moderate hypothermia or deep hypothermic circulatory arrest. From P1 to N2 of the SEPs occurring within 50 ms latency in response to electrical stimulation of the median nerve were recorded over the contralateral postcentral cortex at 5-min intervals using a Neuropack-2 (Nihon Koden, Tokyo, Japan). Normal SEPs were recovered in 247 patients postoperatively; however, 2 of these patients had suffered a cerebral infarction and 1, a transient stroke intraoperatively, demonstrating a false-negative incidence of 1.2%. On the other hand, three different types of abnormal SEPs were recorded postoperatively. P1 and N1 absence, probably caused by a subcortical lesion, was observed in 4 patients; P2 and N2 absence, probably caused by a cortical lesion, was observed in 8 patients; and a flat SEP, representing diffuse damage, was observed in 2 patients. Among these 14 patients with abnormal SEPs, 7 showed no neurologic disturbance at all, demonstrating a false-positive incidence of 50%. Thus, we concluded that when normal SEPs are recovered during weaning from CPB, the incidence of brain damage could be predicted at below 5%. Conversely, when abnormal SEPs are demonstrated, the incidence of brain dysfunction impeding a return to active life is estimated to be about 70%.

Adolescent↗

Bidirectional augmentation of heart rate regulation by autonomic nervous system in rabbits.

Although the characteristics of the static interaction between the sympathetic and parasympathetic nervous systems in regulating heart rate (HR) have been well established, how the dynamic interaction modulates the HR response remains unknown. We therefore investigated dynamic interaction by estimating the transfer function from nerve stimulation to HR using a band-limited Gaussian white-noise technique. The transfer function relating dynamic sympathetic stimulation to HR had characteristics of a second-order low-pass filter. Simultaneous tonic vagal stimulation at 5 and 10 Hz increased gain of the transfer function by 55.0 +/- 40.1 and 80.7 +/- 50.5%, respectively (P < 0.05). The transfer function from dynamic vagal stimulation to HR had characteristics of a first-order low-pass filter. Simultaneous tonic sympathetic stimulation at 5 and 10 Hz increased the gain by 18.2 +/- 17.9 and 24.1 +/- 18.0%, respectively (P < 0.05). Thus interaction augmented dynamic gain bidirectionally, even though it affected mean HR antagonistically. By virtue of this interaction, the autonomic nervous system appears to extend its dynamic range of operation.

Animals↗

Neural arc of baroreflex optimizes dynamic pressure regulation in achieving both stability and quickness.

The baroreflex loop consists of a fast neural arc and a slow mechanical arc. We hypothesized that the neural baroreflex arc compensates the slow mechanical response and thus improves the quality of blood pressure regulation. We estimated the open-loop transfer characteristics of the neural baroreflex arc (HP), i.e., from carotid sinus pressure to sympathetic nerve activity (SNA), and that of the effective peripheral baroreflex arc (Hp), i.e., from SNA to arterial pressure, in anesthetized rabbits. The gain of Hn was constant below 0.12 +/- 0.057 Hz and increased with a slope of 6.1 +/- 0.06 dB/octave above its frequency up to 1 Hz. In contrast, the gain of Hp was constant below 0.071 +/- 0.03 Hz and decreased with a slope of -11.0 +/- 1.48 dB/octave above the frequency. These data indicate that Hn accelerates slow peripheral responses in the frequency range of 0.1-1 Hz. Although too much acceleration in the high-frequency range could result in instability of the system, numerical analysis of the closed-loop baroreflex response indicated that the neural arc optimized arterial pressure regulation in achieving both stability and quickness.

Animals↗

The possibility of active form of vitamins A and D as suppressors on adipocyte development via ligand-dependent transcriptional regulators.

The study aimed to systematically examine the effects of fat soluble vitamins and their analogs on terminal differentiation of adipocytes on the cellular and molecular aspects. It is well known that fat soluble vitamins especially vitamins A and D inhibit the differentiation of adipocytes in cultured cells. Furthermore, it has been revealed that the low level of dietary fat soluble vitamins, especially vitamin A and carotenoid actively stimulate the development of adipose tissue, namely bovine marbling in vivo. We have shown that the expression of retinoic acid receptor (RAR) alpha and gamma, retinoid X receptor (RXR) alpha and beta, and vitamin D receptor (VDR) mRNA were abundant in rat adipose tissue and 3T3-L1 cells. The autoregulated amplification and reduction of RAR, RXR and VDR mRNA by their own ligands, were observed in 3T3-L1 cells. Finally, we proposed the model of vitamins A and D as suppressors on adipocyte development through retinoid/thyroid/vitamin D/fatty acid-activated/peroxisomal proliferator-activated receptor's subfamily.

3T3 Cells↗

[Comparison of life habits and health examination data between smokers and ex-smokers].

Health practice and health examination data were compared between smokers and ex-smokers in 6,076 male subjects, whose ages ranged from 40 to 59 years, who participated in health examinations in 1993 in 17 towns of Gunma Prefecture. A total of 4,629 (76.2%) subjects replied to the interview on health practice and also had health examination data that could be used. The numbers of smokers and ex-smokers were 2,681 and 245, respectively for a total of 2,926 target population. The percentage for those having breakfast daily was significantly higher in ex-smokers than in smokers in the age 40's group (p < 0.01). The percentage for those doing exercise more than one day a week was significantly higher in ex-smokers than in smokers in the age 50's group (p < 0.05). Mean body mass index (BMI) was significantly higher in ex-smokers than in smokers in the age 40's and 50's groups, with p < 0.05 and p < 0.01, respectively. Mean high-density lipoprotein cholesterol (HDLC) was significantly higher in ex-smokers than in smokers in the age 40's group (p < 0.05). The two way analysis of variance on BMI and HDLC was conducted by smoking and drinking factors. BMI was related to only smoking in the age 40's and 50's groups. Smoking and drinking habit related to HDLC in the age 40's group and the latter habit had a relatively large association to HDLC. From the association between BMI and smoking habit, we speculate that exercise was practiced by ex-smokers due to the obesity potential of the ex-smoking status.

Adult↗

[Clinical analysis of embolism with left atrial myxomas].

We conducted a retrospective analysis examining the relationship between the tumor quality and the occurrence of systemic embolization in 16 patients who underwent surgical excision of the left atrial myxoma. Systemic embolization occured in 10 patients (63%) before surgery, in 5 of whom embolic episodes were the first manifestation of the tumor. Cerebral infarction had developed in 7 patients, TIA in 2, myocardial infarction in 2, limb ischemia in 2, and multiple infarctions in the kidney, adrenal gland, spleen and bone marrow in one. A permanent deficit remained in 6 patients (60%). Myxoma was a lobulated and gelatinous type in 9 (90%) of these patients with embolization and a solid type only in one case. When the dignosis of the left atrial myxoma with soft and fragile quality is made by echocardiography, surgical excision should be performed without delay to prevent systemic embolization.

Adolescent↗

[Surgical treatment of aortic valve endocarditis associated with aortic root aneurysm and abscess].

Between Jan. 1979 and Mar. 1996, aortic root abscess and aneurysm were encountered in 10 (34.5%) of the 29 patients who underwent surgical treatment for the aortic valve endocarditis ; native valve endocarditis (NVE) in 8 and prosthetic valve endocarditis (PVE) in 2. Noncoronary sinus was involved in 8 (80%) of 10 patients, left coronary sinus destructed in one, and more than one sinus were involved in one. All patients underwent aortic valve replacement after repair of abscess or aneurysm with suture closure in 5, and patch closure in 3, and its resection in one. Aortic root reconstruction using a valved conduit was required for the repair of aortico-ventricular discontinuity followed debridement of the abscess cavity of almost entire annulus in one PVE patient who consequentry died of LOS and sepsis. There was no operative or postoperative death in the other patients, however, one female patient suddenly died 24 months after surgery. She underwent direct suture closure of left coronary sinus aneurysm and aortic valve replacement with a small-sized prosthetic valve. Suture dehiscence of the orifice of the aneurysm developed immediately after surgery. It is concluded that patch closure of aortic root aneurysm or abscess is recommended so as to avoid narrowing of left ventricular outflow tract and recurrence of aneurysm formation even if its orifice proved to be small.

Abscess↗