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T Kawada

Publications and source records attributed to T Kawada.

At least 73 records · Page 4Linked to original sources
PubMed2000

Closed-loop estimation of the open-loop carotid sinus baroreflex transfer function for the use of animal experiments in space.

In order to develop effective counter measures to cardiovascular maladaptation associated with space flight, it is essential to know how dynamic characteristics of blood pressure regulation are altered in space. The open-loop transfer characteristics of the carotid sinus baroreflex can be divided into the neural arc and peripheral arc transfer functions (Ikeda et al. 1996). The neural arc transfer function represents the dynamic input-output characteristics from arterial pressure (AP) to efferent sympathetic nerve activity (SNA), while the peripheral arc transfer function represents those from SNA to AP. Although AP perturbation according to a white noise sequence can be used to estimate the transfer functions under baroreflex closed-loop conditions (Kwanda et al. 1997), arterial catheter implantation necessary to perturb AP limits the applicability of this method to freely moving animal experiments. To overcome this problem, we explored the closed-loop system identification method using electrical stimulation. We used aortic depressor nerve (ADN) stimulation and rapid pacing (RP) of the heart to perturb the arterial baroreflex system.

Algorithms↗
PubMed1999

Characterization of a novel cDNA sequence encoding invertebrate tachykinin-related peptides isolated from the echiuroid worm, Urechis unicinctus.

Tachykinin is one of the most well-known bioactive peptides found in vertebrates, and tachykinin-related peptides have also been isolated from various invertebrate species. Urechistachykinin I (Leu-Arg-Gln-Ser-Gln-Phe-Val-Gly-Ser-Arg-NH(2)) and II (Ala-Ala-Gly-Met-Gly-Phe-Phe-Gly-Ala-Arg-NH(2)) were purified from the ventral nerve cords of echiuroid worm, Urechis unicinctus. In the present study, we described the characterization of a novel cDNA encoding the urechistachykinin precursor. Amino acid sequence analysis of the deduced polypeptide revealed that the urechistachykinin precursor included seven structurally related peptides, unlike mammalian tachykinin precursors which encode only one or two tachykinin peptides. This is the first identification of an invertebrate tachykinin-related peptide cDNA.

Amino Acid Sequence↗
PubMed1999

Strain- and age-dependent loss of sarcoglycan complex in cardiomyopathic hamster hearts and its re-expression by delta-sarcoglycan gene transfer in vivo.

The delta-sarcoglycan (SG) gene is deleted in hamsters with hereditary cardiomyopathies. Immunological analyses of heart before, but not after, the progression of cardiomyopathy (CM) revealed that the BIO 14.6 strain, a model of hypertrophic CM, heterogeneously preserved alpha- and gamma-SG with loss of beta- and delta-SG. In contrast, the TO-2 strain, a model of dilated CM, did not show either SG. Furthermore, in vivo transfer of the full length delta-SG gene to TO-2 hearts expressed all four SGs. Thus, this age- and strain-dependent features suggest a more feasible setting for TO-2 than BIO 14.6 to verify both CM progression and the efficacy of gene therapy.

Age Factors↗
PubMed1999

Novel therapeutic strategy against central baroreflex failure: a bionic baroreflex system.

BACKGROUND: Central baroreflex failure in Shy-Drager syndrome and traumatic spinal cord injuries results in severe orthostatic hypotension and often confines the patient to the bed. We proposed a novel therapeutic strategy against central baroreflex failure: implementation of an artificial feedback control system able automatically to regulate sympathetic vasomotor tone, that is, a bionic baroreflex system (BBS). With the use of a rat model of central baroreflex failure, we developed the BBS and tested its efficacy. METHODS AND RESULTS: Our prototype BBS for the rat consisted of a pressure sensor placed into the aortic arch, stimulation electrodes implanted into the greater splanchnic nerve, and a computer-driven neural stimulator. By a white noise approach for system identification, we first estimated the dynamic properties underlying the normal baroreflex control of systemic arterial pressure (SAP) and then determined how the BBS computer should operate in real time as the artificial vasomotor center to mimic the dynamic properties of the native baroreflex. The open-loop transfer function of the artificial vasomotor center was identified as a high-pass filter with a corner frequency of 0.1 Hz. We evaluated the performance of the BBS in response to rapid-progressive hypotension secondary to sudden sympathetic withdrawal evoked by the local imposition of a pressure step on carotid sinus baroreceptors in 16 anesthetized rats. Without the BBS, SAP rapidly fell by 49+/-8 mm Hg in 10 seconds. With the BBS placed on-line with real-time execution, the SAP fall was suppressed by 22+/-6 mm Hg at the nadir and by 16+/-5 mm Hg at the plateau. These effects were statistically indistinguishable from those of the native baroreflex system. CONCLUSIONS: These results suggest the feasibility of a BBS approach for central baroreflex failure.

Animals↗
PubMed1999

Precise identification of gene products in hearts after in vivo gene transfection, using Sendai virus-coated proteoliposomes.

Both efficient gene transfer and the exact identification of gene product are required for gene therapy. Gene transfection of green fluorescence protein (GFP) might be useful for the reporter. After in vivo cotransfection of GFP and beta-galactosidase (beta-Gal) genes in Sendai virus-coated proteoliposomes to rat hearts, we compared the sensitivity and specificity of three methods: GFP detection, histochemical staining (HC) of beta-Gal activity, and immunostaining (IS) of the beta-Gal protein. Fluorescence microscopy and double staining of HC and IS revealed that both GFP and IS were equally sensitive and fourfold superior to HC at the peak of gene expression. However, different from skeletal muscle, the GFP of transfected cardiomyocytes showed two demerits: the fluorescence quenching due to the intense staining of beta-Gal activity, and nonspecific autofluorescence from myocardium. Thus, specific IS would be so far the most reliable to identify the gene product in heart.

Animals↗
PubMed1999

Platelet spontaneous aggregation in platelet-rich plasma is increased in habitual smokers.

Cigarette smoking is a well-known risk factor for atherosclerotic disorders. Several authors have suggested that platelet aggregability is important in smoking-induced vascular injury. When platelet-rich plasma is stirred at 37 degrees C in the absence of chemical stimulants, small aggregates of platelets may be formed, but it was difficult to detect small aggregates by conventional aggregometer using optical density. Recent technological advances have made it possible to detect small aggregates by using a newly developed assay system that employs laser light scattering. In the present study, we attempted to measure platelet aggregation by this method, using laser light scattering in 54 nonsmoking healthy males and 51 healthy male habitual smokers who were age matched. In smokers, blood was obtained after 10 hours of smoking abstinence. No significant difference in platelet aggregation was induced by 1 microM or 5 microM of ADP between smokers and nonsmokers. In smokers, plasma fibrinogen levels and the number of small aggregates formed in the absence of chemical stimulants was significantly higher than in nonsmokers. Small aggregates formed in the absence of stimulants correlated positively with the concentrations of von Willebrand factor (vWF) antigen (r=0.2654, p<0.01) and of fibrinogen (r=0.2834, p<0.01). The formation of these small aggregates was inhibited by monoclonal antibody against GPIIb/IIIa blocking fibrinogen binding to GPIIb/IIIa but not inhibited at all by monoclonal antibody against GPIb blocking vWF binding to GPIb. From these results, enhanced platelet aggregability in smokers was confirmed, and it was suggested that GPIIb/IIIa is concerned in platelet spontaneous aggregation, although vWF may not directly influence on the platelet spontaneous aggregation. Since the mechanism of spontaneous aggregation and the effect of increased spontaneous aggregability on the progression of atherosclerosis remains unclear, further study was considered necessary.

Adult↗
PubMed1999

Altered expression of CD45 isoforms in differentiation of acute myeloid leukemia.

Specific expression of different CD45 isoforms can be seen in various stages of differentiation of normal nucleated hematopoietic cells. Association of membrane expression of CD45 isoforms and differential levels of leukemia cells was studied in 91 cases with de novo acute myeloid leukemia (AML). Membrane expression of CD45RA and CD45RO was analyzed by flow cytometry and their expression patterns were compared with AML subtypes classified according to the French-American-British (FAB) classification. CD45RA was essentially expressed in all of the FAB myelocytic subtypes (M0-M3). Its expression in percentage was lower in the most differentiated subtype of AML (M3) when compared with other myelocytic subtypes. CD45RO expression was rarely observed in cases with myelocytic subtypes (1/56 cases of M0, M1, M2, and M3) except for the minimally differentiated myelocytic subtype (M0) or those with potential for differentiation to T-cell lineage where three of 12 cases showed CD45RO expression. When leukemia cells of an M3 case were differentiated to mature granulocytes by treatment of all-trans-retinoic acid, they showed increasing expression of CD45RO. In subtypes with a monocytic component (M4 and M5), both of CD45RA and CD45RO expression were observed and mutually exclusive. When 10 cases of M5 were subdivided by the differential level into undifferentiated (M5a) and differentiated monocytic leukemia (M5b), expression of CD45RA and CD45RO was strictly restricted to cases with M5a and M5b, respectively. These results suggest that CD45 isoform expression in AML characterizes differential levels both in myelocytic and monocytic lineages and specifically disturbed in each subtype. The assessment of CD45 isoform expression appears to provide an insight on biological characteristics and a useful supplementary test for differential diagnosis of AML subtypes.

Acute Disease↗
PubMed1999

Development of a servo-controller of heart rate using a cycle ergometer.

In exercise training, precise control of exercise intensity would maximize the training efficacy while minimizing risks. To adjust work rate, heart rate (HR) has been used as a measure of exercise intensity. Thus, we developed a servo-controller of HR using a cycle ergometer. After estimating the transfer function from work rate to HR, we optimized feedback parameters for achieving a quick and stable HR response by means of a computer simulation. We then examined the performance of the servo-controller of HR in 55 healthy volunteers. We set the target HR at 60% and 75% of the age-predicted maximum HR. Times required for HR to reach 90% of the target HR were 136 +/- 33 and 137 +/-22s in the respective protocols. Standard deviations of the steady-state difference between the target and measured HRs were 2.5 +/- 0.6 and 3.8 +/- 1.1 beats/min. We conclude that the developed servo-controller makes it possible to precisely regulate HR and, thereby, exercise intensity.

Adult↗
PubMed1999

Argatroban, an attractive anticoagulant, for left heart bypass with centrifugal pump for repair of traumatic aortic rupture.

Systemic heparinization often increases the risk of fatal bleeding from other injured organs in surgical repair of the aorta using extracorporeal circulation in patients with traumatic aortic rupture associated with multisystem injuries. We used an antithrombin agent, argatroban, as an alternative anticoagulant in left heart bypass with the Bio-Medicus centrifugal pump in 7 of 9 recent patients who underwent aortic repair using left heart bypass. All these patients survived without obvious evidence of systemic thromboembolization. Surgical treatments for other organ injuries were carried out in 3 patients concomitantly or immediately after aortic repairs without undue blood loss. Argatroban may have a complementary effect for preventing thrombus formation without aggravating bleeding tendency because of its monotarget specificity to thrombin. We believe intravenous administration (0.5 to 2 micrograms/kg/min) of argatroban is a safe anticoagulant for left heart bypass in repairs of traumatic aortic rupture associated with multiple organ injuries.

Adolescent↗
PubMed1999

The orosensory recognition of long-chain fatty acids in rats.

To determine the selectivity of long-chain fatty acid (LCFA) in the oral cavity, short-term (5 min) two-bottle tests were conducted in rats. Fifteen male Wistar rats were given oleic acid, linoleic acid, linolenic acid, and their derivatives. All compounds used were 99% pure. The concentration of test fluids was made 1% in 0.3% xanthan gum to minimize postingestive and textural effects. The rats preferred LCFA fluids to the control of 0.3% xanthan gum solution. The preference order of LCFA was linolenic acid > linoleic acid > oleic acid. Four LCFA derivatives (methyl oleate, oleyl alcohol, methyl linoleate, and linolyl alcohol), triolein, and capric acid were not preferred to LCFA, but LCFA derivatives were preferred to the control of xanthan gum solution. These studies suggest that rats select LCFA from olfactory or gustatory cues that are related to both the carbon chain and carboxylate group.

Animals↗
PubMed1999

Effects of ouabain on in situ cardiac sympathetic nerve endings.

Using dialysis technique, the effects of ouabain on in situ cardiac sympathetic nerve endings were examined in anesthetized cats. Dialysis probes were implanted in the left ventricular myocardium, and the concentration of dialysate norepinephrine (NE) was used as an indicator of NE output at the cardiac sympathetic nerve ending. Locally applied ouabain dose-dependently (1, 10, 100 microM) increased dialysate NE levels. This finding suggested that ouabain causes an increase in NE efflux without any requirement for prior mobilization of NE from vesicular stores. Transection of sympathetic nerves innervating the heart, was without effect on the ouabain (100 microM)-induced increase in NE efflux. Pretreatment with a Ca2+-channel blocker, omega-conotoxin GVIA (10 microg/kg i.v.) suppressed the ouabain-induced NE efflux. These data suggested that ouabain opened N-type calcium channels coupled to NE release without centrally mediated neural transmission. Furthermore, ouabain-induced NE efflux was suppressed by pretreatment with desipramine (neuronal NE uptake inhibitor, 100 microM). Our data suggest that the two mechanisms (exocytosis and carrier-mediated outward transport), to the same extent, contributed to the amount of NE efflux evoked by ouabain in in situ cardiac sympathetic nerve endings.

Animals↗
PubMed1999

Analysis of strain distribution in the medial collateral ligament using a photoelastic coating method.

The strain distribution over the entire medial collateral ligament (MCL) was measured using a photoelastic coating method. This new approach utilized a polyurethane monomer as a photoelastic coating film. The initial experiments investigating MCL strain measurement showed that this film had a high sensitivity for strain and good adhesion to the ligament. It was confirmed that strain distribution could be obtained qualitatively over the entire ligament using this method. The mechanism of MCL injury was studied by applying this polyurethane coating film to the entire MCL in a femur-MCL-tibia complex. When simple tension was applied to the complex, strain concentrations were centred at the tibial insertion site, and all the specimens ruptured at the MCL tibial insertion site. With application of a valgus bending moment, increased strain was seen in the MCL from the medial femoral condyle to the medial epicondyle. Histological analysis demonstrated midsubstance ligament ruptures in this same region. For both tests, rupture sites and increased strain concentration sites correlated. In addition, an impingement phenomenon of the MCL on the medial femoral condyle can be seen during application of valgus force, and this phenomenon may explain the higher incidence of MCL injuries on the femoral side seen in the clinical setting. This polyurethane coating method allows for direct and visual measurements, and can qualitatively measure the strain behaviour over the entire MCL surface. This new technique represents a significant improvement over previous point-by-point strain measurement methods.

Animals↗
PubMed1999

Nicotine induces uncoupling protein 1 in white adipose tissue of obese mice.

OBJECTIVE: To test the hypothesis that nicotine not only activates uncoupling protein1 (UCP1) in brown adipose tissue (BAT), but also induces UCP1 in white adipose tissue (WAT), which contributes to the mitigation of obesity in obese mice. DESIGN: Weights of the whole body, the gastrocnemius muscle, interscapular BAT and subcutaneous and retroperitoneal WAT, food intake and the mRNA and protein of UCP1 in these tissues were measured and immunohistochemistry using antiserum against UCP1 was also performed in obese yellow KK mice treated with nicotine for 6 months and control mice treated with physiological saline. RESULTS: Obese mice treated with nicotine for 6 months, compared with those injected with saline, weighed significantly less (P < 0.01) and had smaller subcutaneous and retroperitoneal WAT pads (P < 0.01), while obese mice that received nicotine ate less (P < 0.05) than those injected with saline. In mice treated with nicotine, the mRNA and protein of UCP1 was detected not only in BAT, but also in subcutaneous and retroperitoneal WATs. Immunohistochemically, the BAT of obese mice contained large lipid droplets and appeared rather WAT-like, but changed to typical brown adipocytes after nicotine treatment. The fat pads of nicotine-treated mice contained many multilocular cells that were positive for UCP1. CONCLUSION: Nicotine not only activates UCP1 in BAT, but also induces UCP1 in WAT and decreases food intake, which contributes to the mitigation of obesity.

Adipocytes↗
PubMed1999

Allyl-containing sulfides in garlic increase uncoupling protein content in brown adipose tissue, and noradrenaline and adrenaline secretion in rats.

The effects of garlic supplementation on triglyceride metabolism were investigated by measurements of the degree of thermogenesis in interscapular brown adipose tissue (IBAT), and noradrenaline and adrenaline secretion in rats fed two types of dietary fat. In Experiment 1, rats were given isoenergetic high-fat diets containing either shortening or lard with or without garlic powder supplementation (8 g/kg of diet). After 28 d feeding, body weight, plasma triglyceride levels and the weights of perirenal adipose tissue and epididymal fat pad were significantly lower in rats fed diets supplemented with garlic powder than in those fed diets without garlic powder. The content of mitochondrial protein and uncoupling protein (UCP) in IBAT, and urinary noradrenaline and adrenaline excretion were significantly greater in rats fed a lard diet with garlic powder than in those fed the same diet without garlic. Other than adrenaline secretion, differences due to garlic were significant in rats fed shortening, also. In Experiment 2, the effects of various allyl-containing sulfides present in garlic on noradrenaline and adrenaline secretion were evaluated. Administration of diallyldisulfide, diallyltrisulfide and alliin, organosulfur compounds present in garlic, significantly increased plasma noradrenaline and adrenaline concentrations, whereas the administration of disulfides without allyl residues, diallylmonosulfide and S-allyl-L-cysteine did not increase adrenaline secretion. These results suggest that in rats, allyl-containing sulfides in garlic enhance thermogenesis by increasing UCP content in IBAT, and noradrenaline and adrenaline secretion.

Adipose Tissue, Brown↗
PubMed1999

Acute effect of tumor necrosis factor-alpha is minimal on mechanics but significant on energetics in blood-perfused canine left ventricles.

OBJECTIVES: We hypothesized that tumor necrosis factor-alpha (TNF-alpha) acutely alters left ventricular mechanoenergetics in blood-perfused hearts. To test this hypothesis, we examined the relation between left ventricular mechanics and energetics, both before and after infusion of TNF-alpha. DESIGN: Prospective, experimental study. SETTING: Research laboratory. SUBJECTS: Nine isolated, blood-perfused canine hearts. INTERVENTIONS: Recombinant human TNF-alpha (90 microg/min) was infused into the coronary circulation of the isolated hearts for 20 mins. MEASUREMENTS AND MAIN RESULTS: In the isolated, cross-circulated, blood-perfused canine left ventricles, left ventricular contractility was assessed through measurement of end-systolic elastance (Ees). Energetics were examined in terms of the end-systolic pressure-volume area-myocardial oxygen consumption (MVo2) relation. TNF-alpha concentration in coronary venous blood was >1000 ng/mL throughout the experiments. Nevertheless, infusion of TNF-alpha barely affected contractility acutely, i.e., there was a minimal decrease during the infusion (8.1+/-2.8% at 10 mins, p < .01) and a minimal increase after the infusion (11.2+/-2.5% at 10 mins, p< .01). Neither did the TNF-alpha infusion affect the slope of the end-systolic pressure-volume area-MVo2 relation. This finding indicated that the chemomechanical conversion efficiency remained unchanged. However, TNF-alpha infusion significantly increased the oxygen cost of contractility by 40% (1.25+/-0.13 vs. 1.75+/-0.24 mL oxygen.mL/mm Hg/beat, p< .05), indicating that MVo2 for the excitation-contraction coupling increased. CONCLUSIONS: TNF-alpha minimally alters left ventricular mechanics, but significantly changes energetics. The latter effect may result from changes in intracellular calcium handling.

Animals↗
PubMed1999

A staging system for multiple myeloma based on the morphology of myeloma cells.

The morphology of myeloma cells is reported to be one of the prognostic factors in multiple myeloma (MM) patients. We analyzed the prognostic factors, including morphological classification, in 292 patients with MM in order to select poor-risk patients who should be considered candidates for early intensive chemotherapy, including stem cell transplantation. Multivariate analysis was applied to 90 patients diagnosed between 1989 and 1996, because serum beta-2-microglobulin (beta2M) has been measured regularly since 1989, and showed that serum albumin, serum beta2M, and the morphology of myeloma cells predicted survival. According to these factors, patients were divided into 3 risk groups; a high-risk group (14%), a intermediate-risk group (46%) and a low-risk group (40%). There were significant differences between survival times in these 3 groups (median survival: high-risk, 16; intermediate-risk, 22; and low-risk, 44 months).

Aged↗
PubMed1999

New simple methods for isolating baroreceptor regions of carotid sinus and aortic depressor nerves in rats.

We developed new methods for isolating in situ baroreceptor regions of carotid sinus and aortic depressor nerves in halothane-anesthetized rats. After ligation of the root of the external carotid artery, the internal carotid and pterygopalatine arteries were embolized with two ball bearings of 0.8 mm in diameter. Bilateral carotid sinus pressures were changed between 60 and 180 mmHg in 20-mmHg steps lasting 1 min each. The sigmoidal steady-state relationship between aortic and carotid sinus pressures in 11 rats indicated the maximum gain of the carotid sinus baroreflex to be -2. 99 +/- 0.75 at 120 +/- 5 mmHg. An in situ isolation of the baroreceptor area of the right aortic depressor nerve could be made by ligation of the innominate, common carotid, and subclavian arteries in 9 rats. Pressure imposed on the subclavian baroreceptor was altered between 40 and 180 mmHg in 20-mmHg steps lasting 1 min each. The sigmoidal steady-state relationship between the aortic depressor nerve activity and imposed pressure showed that the baroreceptor gain peaked at 118 +/- 4 mmHg. We established an easy approach to the rat baroreflex and baroreceptor research.

Animals↗