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Biomedical subjects

T Kawada

Publications and source records attributed to T Kawada.

At least 37 records · Page 2Linked to original sources
PubMed2001

Integrative sympathetic baroreflex regulation of arterial pressure.

The baroreflex system is the most important negative feedback control system functioning physiologically to attenuate the effects of rapid perturbation in arterial pressure. However, the complexity of the system resulting from the closed-feedback loop, nonlinearity, and system memory makes detailed quantitative characterization of the baroreflex system difficult. To overcome such limitations, we proposed a framework to decompose the baroreflex loop into two major arcs, that is, the mechanoneural arc and neuromechanical arc. Steady state analysis indicated that such decomposition allowed us to analytically determine the operating point by equilibrating two respective function curves. Dynamic analysis suggested that the mechanoneural arc accelerated the slow mechanical response of the neuromechanical arc. The acceleration mechanism in the mechanoneural are optimized arterial pressure regulation in achieving both stability and quickness. Establishment of such an integrative framework allowed the development of an artificial feedback control system able to regulate sympathetic vasomotor tone.

Animals↗
PubMed2001

Vagosympathetic interactions in ischemia-induced myocardial norepinephrine and acetylcholine release.

To elucidate the pathophysiological roles of vagosympathetic interactions in ischemia-induced myocardial norepinephrine (NE) and acetylcholine (ACh) release, we measured myocardial interstitial NE and ACh levels in response to a left anterior descending coronary occlusion in the following groups of anesthetized cats: intact autonomic innervation (INT, n = 7); vagotomy (VX, n = 6); local administration of atropine (Atro, n = 6); transection of the stellate ganglia (TSG, n = 5); local administration of phentolamine (Phen, n = 6); and combined vagotomy and transection of the stellate ganglia (VX+TSG, n = 5). The maximum NE release was enhanced in the VX group (141 +/- 30 nmol/l, means +/- SE, P < 0.05) compared with the INT group (61 +/- 12 nmol/l). Neither the Atro (50 +/- 24 nmol/l) nor VX+TSG groups (84 +/- 25 nmol/l) showed enhanced NE release. The maximum ACh release was unaltered in the TSG and Phen groups compared with the INT group (19 +/- 4, 18 +/- 4, and 13 +/- 3 nmol/l, respectively). These findings indicate that the cardiac vagal afferent but not efferent activity reduced the ischemia-induced myocardial NE release. In contrast, the cardiac sympathetic afferent and efferent activities played little role in the ischemia-induced myocardial ACh release.

Acetylcholine↗
PubMed2001

Differential dynamic baroreflex regulation of cardiac and renal sympathetic nerve activities.

Although regional difference in sympathetic efferent nerve activity has been well investigated, whether this regional difference exists in the dynamic baroreflex regulation of sympathetic nerve activity remains uncertain. In anesthetized, vagotomized, and aortic-denervated rabbits, we isolated carotid sinuses and randomly perturbed intracarotid sinus pressure (CSP) while simultaneously recording cardiac (CSNA) and renal sympathetic nerve activities (RSNA). The neural arc transfer function from CSP to CSNA and that from CSP to RSNA revealed high-pass characteristics. The increasing slope of the transfer gain in the frequencies between 0.03 and 0.3 Hz was significantly greater for CSNA than for RSNA (2.96 +/- 0.72 vs. 1.64 +/- 0.73 dB/octave, P < 0.01, n = 9). The difference was hardly explained by the difference in static nonlinear characteristics of CSP-CSNA and CSP-RSNA relationships or by the difference in conduction velocities in the multifiber recording. These results indicate that the central processing in the brain stem differs between CSNA and RSNA. The neural arc of the baroreflex may exert differential effects on the heart and kidney in response to dynamic baroreflex activation.

Animals↗
PubMed2001

Dynamic sympathetic control of atrioventricular conduction time and heart period.

Although power spectra of R-R and P-R intervals in response to random respiration show similar frequency distributions, the way in which dynamic sympathetic regulation contributes to such similarity remains unknown. We estimated the transfer function from sympathetic stimulation to the atrioventricular interval (AV conduction time; T(AV)) with and without constant atrial pacing in seven anesthetized cats. The transfer function from sympathetic stimulation to T(AV), except for absolute gain values, approximated a low-pass filter similar to that from sympathetic stimulation to the A-A interval (heart period; T(AA)). The 90%-rise times did not differ between the T(AA) and T(AV) step responses (32.3 +/- 1.8 vs. 29.6 +/- 3.2 s). Constant pacing augmented the T(AV) step response (-0.58 +/- 0.10 vs. -0.86 +/- 0.12 ms/Hz, P < 0.05) without affecting the 90%-rise time. These findings suggest that the dynamic characteristics of sympathetic control are similar between T(AA) and T(AV) despite the different electrophysiological mechanisms determining T(AA) and T(AV). A numerical simulation indicated that if the dynamic characteristics of the sympathetic control do not match between T(AA) and T(AV), a critical condition for initiation of reentrant tachycardia would be encountered.

Animals↗
PubMed2001

In vivo assessment of acetylcholine-releasing function at cardiac vagal nerve terminals.

We examined whether the ACh concentration measured by cardiac microdialysis provided information on left ventricular ACh levels under a variety of vagal stimulatory and modulatory conditions in anesthetized cats. Local administration of KCl (n = 5) and ouabain (n = 7) significantly increased the ACh concentration in the dialysate to 4.3 +/- 0.8 and 7.3 +/- 1.3 nmol/l, respectively, from the baseline value of 0.6 +/- 0.5 nmol/l. Intravenous administration of phenylbiguanide (n = 5) and phenylephrine (n = 6) significantly increased the ACh concentration to 5.4 +/- 0.9 and 6.0 +/- 1.5 nmol/l, respectively, suggesting that the Bezold-Jarisch and arterial baroreceptor reflexes affected myocardial ACh levels. Modulation of vagal nerve terminal function by local administration of tetrodotoxin (n = 6), hemicholinium-3 (n = 6), and vesamicol (n = 5) significantly suppressed the electrical stimulation-induced ACh release from 20.4 +/- 3.9 to 0.6 +/- 0.1, 7.2 +/- 1.9, and 2.7 +/- 0.6 nmol/l, respectively. Increasing the heart rate from 120 to 200 beats/min significantly reduced the myocardial ACh levels during electrical vagal stimulation, suggesting a heart rate-dependent washout of ACh. We conclude that ACh concentration measured by cardiac microdialysis provides information regarding ACh release and disposition under a variety of pathophysiological conditions in vivo.

Acetylcholine↗
PubMed2001

Comparison of suppressive potency between prednisolone and prednisolone sodium succinate against mitogen-induced blastogenesis of human peripheral blood mononuclear cells in-vitro.

Clinically, both prednisolone and prednisolone sodium succinate are widely used as immunosuppressive agents for the treatment of various allergic disorders. However, whether prednisolone sodium succinate itself has immunosuppressive or anti-inflammatory effects is unclear, and prednisolone sodium succinate may exhibit its efficacy only after hydrolytic conversion to prednisolone in-vivo. If this is the case, the impairment of prednisolone sodium succinate conversion to prednisolone in some clinical conditions may attenuate the efficacy of prednisolone sodium succinate. We therefore compared the pharmacological efficacy of prednisolone with that of prednisolone sodium succinate in-vitro using human peripheral blood mononuclear cells (PBMCs). PBMCs were obtained from 5 healthy subjects and 1 patient with pneumonia. The cells were incubated in the presence of concanavalin A and the cell growth was estimated by 3-(4,5-dimethyl thiazo-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Both prednisolone and prednisolone sodium succinate dose-dependently suppressed PBMC blastogenesis. Mean (s.d.) prednisolone and prednisolone sodium succinate IC50 (concentration of drug that gave 50% inhibition of cell growth) values were 580.0 (1037.9) and 3237.1 (4627.3) nM, respectively. The ratio of prednisolone IC50/prednisolone sodium succinate IC50 ranged from 0.005 to 0.230. Thus, prednisolone sodium succinate potency was markedly lower than that of prednisolone. After incubation of PBMCs with 100 microM prednisolone sodium succinate, 22.7-42.9 microM prednisolone was liberated into the culture medium, as determined by HPLC. The ratio of prednisolone liberation from prednisolone sodium succinate was not affected by the presence of fetal bovine serum or PBMC, or both, in the culture medium. These results suggested that the PBMC-suppressive effects of prednisolone sodium succinate might be due, at least partially, to prednisolone liberated from prednisolone sodium succinate into the culture medium. Prednisolone sodium succinate can be converted to prednisolone in the absence of serum or PBMCs, but the ratio of this conversion was very slow (t(1/2) > 4 days). Therefore, impairment of the enzymatic conversion of prednisolone sodium succinate to prednisolone in some pathological conditions such as liver diseases may result in attenuation of the clinical efficacy of prednisolone sodium succinate.

Adult↗
PubMed2001

[Physiological and pharmacological function of PPARs].

The finding of nuclear receptors has greatly enhanced our understanding of gene regulation by lipophilic hormones such as steroids, thyroxine, vitamin D and retinoids. These receptors comprise a superfamily of transcription factors containing highly related DNA-binding domains. In mammals, the peroxisome proliferator-activated receptor (PPAR) family of nuclear hormone receptors consists of three subtypes by separate genes: PPAR alpha, PPAR delta (also referred to as hNUC1 or PPAR beta), and PPAR gamma. PPARs have been associated with several distinct biological programs. PPARs function as a heterodimer with the retinoid X receptor. This complex binds to sequences termed direct repeat-1 response element in enhancer sites of regulated genes and activates transcription upon ligand and coactivator binding. Three different PPAR subtypes have specific roles in different organs. PPAR alpha, mainly expressed in liver, plays an important role in fatty acid metabolism. PPAR gamma predominantly is expressed in adipose cells. PPAR delta displays a high level of expression in lipid-metabolizing organs such as small intestine, heart and adipose tissue. Naturally occurring and synthetic molecules (anti-hyperlipidemia and diabetic drugs) that are ligands for these nuclear receptors control transcriptional activity of PPARs. We believe that the pharmacological and genomic researches on PPAR will develop powerful tools for prevention and medical care against common diseases.

Animals↗
PubMed2001

Inhibitory effect of monoacylglycerol on fatty acid uptake into rat intestinal epithelial cells.

We investigated the influence of glycerol esters on oleic acid uptake into IEC-6 cells. Monoolein, especially 2-monoacylglycerol, significantly inhibited the cellular uptake. Although diolein slightly inhibited the oleic acid uptake, triolein, glycerol and monooctanoate had no effect. These results suggest that after lipid digestion in the intestine, long-chain fatty acid uptake may be influenced by another digestive product, 2-monoacylglycerol.

Animals↗
PubMed2001

Changes of pyridine nucleotide levels during adipocyte differentiation of mouse 3T3-L1 cells.

The levels of NAD and NADP were measured in 3T3-L1 cells during a differentiation from preadipocytes to adipocytes. The cells were grown in the ordinary medium and differentiated in the medium by adding dexamethasone, 1-methyl-3-isobutylxanthine, and insulin for 2 days, and then they were grown in the medium by adding only insulin for another 8 days to accumulate fat. The levels of cellular NAD and NADP increased abruptly with days after differentiation, and the levels of NAD and NADP reached maximum at day 7, and at day 10 the values were decreased compared with the maximum values. These results suggest that expression of the pyridine nucleotide biosynthesis genes is induced in the differentiation process.

1-Methyl-3-isobutylxanthine↗
PubMed2001

Laterality in direct and indirect inotropic effects of sympathetic stimulation in isolated canine heart.

Although sympathetic nerve stimulation is known to increase ventricular contractility, concomitant increases in heart rate (HR) make it difficult to separate its direct inotropic effect from indirect inotropic effect through a force-frequency mechanism. We stimulated the stellate ganglia in 8 isolated canine hearts with functional sympathetic nerves. Right sympathetic stimulation at 10 Hz increased ventricular end-systolic elastance (E(es)) by 95.7 +/- 7.5% (p < 0.001) and HR by 32.5 +/- 4.2% (p < 0.05). In contrast, left sympathetic stimulation at 10 Hz increased E(es) by 70.7 +/- 6.5% (p < 0.001) without significant changes in HR. Preventing the chronotropic response by fixed-rate pacing attenuated the E(es) response to right sympathetic stimulation at 5 Hz (52.0 +/- 5.1 vs. 22.8 +/- 2.8%, p < 0.001), but not to left sympathetic stimulation at 5 Hz (54.5 +/- 3.4 vs. 53.3 +/- 2.2%, NS). In the isolated canine heart, the right sympathetic nerve affected E(es) by both the direct inotropic effect and the indirect HR-dependent inotropic effect. In contrast, the left sympathetic nerve regulated E(es) primarily by its direct inotropic effect.

Animals↗
PubMed2001

Biochemical and physiological characteristics of fat cell.

Since animals are under constant threat of starvation, storage of energy sources inside the body is essential for various activities. Therefore, animals exhibit highly sophisticated mechanisms for storing energy inside their bodies in adipose tissue. However, in humans it has been clarified that fat cell (adipocyte, which comprises adipose tissues) differentiation and the extent of subsequent fat accumulation (hypertrophy of cells) are closely associated with the occurrence and advancement of various diseases resulting from obesity. Moreover, progress in biochemical studies with respect to adipocyte in recent years has rapidly clarified new functions and differentiation mechanisms of adipocytes. Interesting points, in particular, are the function of white adipocytes as "secreting cells" and the molecular mechanism of adipocyte differentiation via the nuclear receptors. Consequently, adipose tissue is being targeted to prevent or treat many common diseases. This paper summarizes recent knowledge on characteristics, differentiation and proliferation of adipocytes and the mechanisms by which adipocytes are regulated.

Adipocytes↗
PubMed2001

[Leiomyoma of the esophagus shown as a cervical tumor].

A 44-year-old female was admitted to our hospital because of the left cervical tumor. Radiologic examination showed that the tumor was 5 cm in diameter and was inhomogeneous. The tumor was spread to the upper mediastinum. Esophagoscopy showed that the tumor was covered by the normal mucosa. Percutaneous fine needle biopsy did not appear the histopathological diagnosis. The patient underwent surgical resection through the cervical approach and the tumor was located between the mucosal and muscular layers of the esophagus. The tumor was enucleated without any complication. Histopathological diagnosis was leiomyoma. Postoperative course was uneventful. Expecting diagnosis and positive complete resection is recommended for leiomyoma of the esophagus.

Adult↗
PubMed2001

[Whole blood flow cytometry for detection of activated platelets. I. Platelet identification, blood collection and storage].

In order to assess platelet activation by flow cytometry and activation-dependent monoclonal antibodies, a minute volume(2.5 microliters) of citrated whole blood was mixed for 15 minutes with a cocktail of monoclonal antibodies(MoAb), including PAC1, (a MoAb specific for fibrinogen receptors), and a MoAb against CD62P, (an alpha-granule membrane protein which associates with platelet surface membranes when platelets are activated). After fixation with 1% formaldehyde, the percentage of platelets positive for PAC1 and/or MoAb-CD62P was measured by flow cytometry. Even in resting platelets without stimulation, about 15% of platelets were found to be PAC1-positive and 0.6% of platelets were CD62P-positive. If there was a one-minute delay after needle puncture and before blood collection, the number of PAC1-positive platelets was increased compared to that of blood obtained immediately after puncture. If blood was allowed to stand at room temperature, there was a gradual increase in the number of PAC1-positive platelets, and after 60 minutes, this increase became statistically significant. The addition of Iloprost, (a prostacyclin analogue), immediately after venipuncture did not completely prevent the increase in PAC1-positive platelets after 60 minutes. If the inhibitor was added after first incubating for 60 minutes, however, the percentage of PAC1-positive platelets was reduced to preincubation value. Although flow cytometry is a simple and powerful tool to assess platelet activation, there remain several methodological problems to be resolved before this method may be employed in routine clinical use.

Adult↗
PubMed2001

[Incomplete resection for primary non-small cell lung cancer].

A superior outcome is observed for cases of complete resection compared with that of incomplete resection. The reason and the countermeasure of the incomplete resection for lung cancer were analyzed. During 12 years, 274 patients with primary non-small cell lung cancer were surgically treated. Two hundred and forty-eight patients underwent complete resection and 26 incomplete resection. Three-year survival was 62% for patients with complete resection and 17% for patients with incomplete resection. Survival rates were not different between the paroative reduction surgery and the exploratory thoracotomy. Tiny but multiple pleural dissemination or small amount of the malignant pleurfal effusion was not able to detect preoperatively. In these cases, preoperative thoracoscopic observation may useful for avoiding the meaningless thoracotomy. Postoperative radiochemotherapy may improve the prognosis if the therapy is effective. Chemotherapy on the basis of the sensitivity assay is warranted.

Aged↗
PubMed2000

Cyanide intoxication induced exocytotic epinephrine release in rabbit myocardium.

Cyanide intoxication, which has been used as a model of energy depletion at cardiac sympathetic nerve terminals, causes non-exocytotic release of norepinephrine (NE). However, the effect of cyanide intoxication on cardiac epinephrine (Epi) release remains unknown. Using cardiac microdialysis in the rabbit, we measured dialysate Epi and NE concentrations as indices of myocardial interstitial Epi and NE levels, respectively. Local administration of sodium cyanide (30 mM) through the dialysis probe increased both Epi and NE levels (from 11.3+/-2.3 to 32.3+/-4.4 pg/ml and from 33.6+/-6.1 to 389.0+/-71.8 pg/ml, respectively, mean+/-S.E., P<0.01). Local desipramine (100 microM) administration suppressed the cyanide induced NE response without affecting the Epi response. In contrast, local omega-conotoxin GVIA (10 microM) administration partially suppressed the cyanide induced NE response and totally abolished the Epi response. In conclusion, cyanide intoxication causes N-type Ca(2+) channel dependent exocytotic Epi release as well as inducing N-type Ca(2+) channel independent non-exocytotic NE release.

Adrenergic Uptake Inhibitors↗
PubMed2000

Local epinephrine release in the rabbit myocardial interstitium in vivo.

Although several investigations have suggested cardiac epinephrine (Epi) release, local Epi release in the myocardial interstitium in vivo has not been measured. Using cardiac microdialysis in the rabbit, we measured dialysate Epi and norepinephrine (NE) concentrations as indices of myocardial interstitial Epi and NE levels, respectively. Exocytotic release induced by local administration of KCl (100 mM) through the dialysis probe increased Epi to 24.2 +/- 13.2 pg/ml from a control value of 3.2 +/- 3.6 pg/ml (P < 0.01, n = 6). Non-exocytotic release induced by the local administration of tyramine (10 microg/ml) also increased Epi to 34.6 +/- 15.3 pg/ml (p < 0.05 from control, n = 6). We conclude that Epi can be released via both exocytotic and non-exocytotic release mechanisms from the heart.

Animals↗