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Biomedical subjects

K Okada

Publications and source records attributed to K Okada.

At least 685 records · Page 38Linked to original sources

Neural mechanism of depressor responses of arterial pressure elicited by acupuncture-like stimulation to a hindlimb in anesthetized rats.

The effects of acupuncture-like stimulation of a hindlimb on renal sympathetic nerve activity (RNA) as well as mean arterial blood pressure (MAP) were examined in anesthetized rats. An acupuncture needle (diameter of 160 microns) was inserted into the skin of a hindlimb and underlying muscles to a depth of 5 mm and was twisted at about 1 Hz. Under deep anesthetic condition, in about 70% of trials, acupuncture-like stimulation for 60 s induced a decrease in MAP which was accompanied by a decrease in RNA. Acupuncture-like stimulation applied to the muscles alone, but not to the skin alone, induced inhibition of RNA and MAP. Transection of sciatic and femoral nerves ipsilateral to the hindlimb stimulation completely abolished the responses of RNA and MAP. The hindlimb stimulation excited the femoral and common peroneal afferent nerves. In spinalized animals, the hindlimb stimulation did not produce any changes in RNA and MAP. The results indicate that the decrease in MAP induced by acupuncture-like stimulation of a hindlimb is a reflex response. The afferent pathway is composed of hindlimb muscle afferents while the efferent pathway is composed of sympathetic vasoconstrictors including the renal nerves. Endogenous opioids may not be involved in the present reflex, because an intravenous injection of naloxone, an antagonist of the opioid receptors, did not influence the reflex.

Acupuncture Therapy↗

High-grade surface osteosarcoma of the humerus.

We presented a case of high-grade surface osteosarcoma of the humerus in a 12-year-old girl and the results of our analysis of 26 cases reported in the literature. Twelve of the 21 patients for whom substantial follow-up information was reported had died of the disease, and the results of the analysis regarding the efficacy of chemotherapy and medullary involvement were ambiguous. It is emphasized that high-grade surface osteosarcoma is a distinct entity, since it is associated with a poorer prognosis than other osteosarcomas arising on the surface of bone.

Bone Neoplasms↗

Acute left atrial thrombus causing cardiogenic shock following mitral valve replacement: report of a case.

We report herein the rare case of a 53-year-old woman who developed cardiogenic shock due to an acute left atrial thrombus following replacement of the mitral valve. A definitive diagnosis was not able to be made using precordial echocardiography because of the broad, flat shape of the thrombus; however, transesophageal echocardiography imaged the thrombus in detail. The patient was initially stabilized by percutaneous cardiopulmonary support after which a thrombectomy was successfully performed.

Echocardiography, Transesophageal↗

Analysis of target organs for the latency of murine cytomegalovirus DNA using specific pathogen free and germfree mice.

Cytomegalovirus (CMV) establishes a latent infection in its host; however, the organ sites of viral latency and its mechanism still remain to be fully clarified. To elucidate this issue, a latent infection with murine (M) CMV was attempted to induce in mice and the organ sites of the latent viral genome were examined for more than one year by a polymerase chain reaction (PCR). As a result, latent MCMV DNA was detectable in both the lung and the spleen as late as 59 weeks after infection. The heart was also observed to be a target organ of latent MCMV DNA, though the amount of viral DNA was much less than that seen in the lung and spleen. In germfree (GF) mice, on the other hand, no such latent viral DNA was observed in the spleens, while it was seen, but to a significantly smaller degree, in the lungs and the hearts than in the same organs of specific pathogen-free (SPF) mice. The amount of infectious virions generated in the host appeared to be almost equal between the GF and SPF mice. The above findings therefore suggest that the spleen, lung and heart are target organs for MCMV latency and the indigenous bacterial flora, which are not colonizing in GF mice, play an important role in the establishment of such viral latency in SPF mice.

Amino Acid Sequence↗

Methylprednisolone inhibits increase of interleukin 8 and 6 during open heart surgery.

It has been reported that interleukin 8 (IL-8) and interleukin 6 (IL-6) are two of the chemical mediators causing myocardial injury. It is not clear whether treatment with corticosteroids in vitro in these patients can prevent the production of interleukin 8 and 6. This prospective study was conducted to investigate whether methylprednisolone (MP) pretreatment (30 mg.kg-1 before CPB and before declamping of aorta) influenced the production of IL-8 and 6 in the peripheral circulation in 27 patients undergoing elective coronary artery bypass surgery. The IL-8 and IL-6 concentrations were measured by ELISA kit. We also studied the effect of MP pretreatment on postoperative cardiac function. Serum concentration of IL-8 in non-MP-treated patients (37 +/- 44 pg.ml-1 preoperatively) increased to 169 +/- 86 pg.ml-1 60 min after declamping of the aorta (P < 0.001). The increase was greater than the increase from 22 +/- 8.9 pg.ml-1 to 52 +/- 35 pg.ml-1 in the MP-treated patients (P < 0.01). Serum IL-6 concentration in non-MP-treated patients increased from the preoperative value of 59 +/- 30 pg.ml-1 to 436 +/- 143 pg.ml-1 60 min after declamping of the aorta (P < 0.001). The increase was greater than the increase from 36 +/- 15 pg.ml-1 to 135 +/- 85 pg.ml-1 in the MP-treated patients (P < 0.01). Furthermore, postoperative cardiac index in MP-treated patients (3.6 +/- 1.1 L.min-1.m-2) was higher than 2.3 +/- 0.8 L.min-1.m-2 of non MP-treated patients (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac Output↗

Successful 24-hour rabbit heart preservation by hypothermic continuous coronary microperfusion with oxygenated University of Wisconsin Solution.

BACKGROUND: This study assessed whether a combination of hypothermic continuous coronary microperfusion and oxygenated University of Wisconsin Solution (UWS) improves postischemic functional recovery and minimizes myocardial tissue edema. METHODS: Isolated rabbit hearts were divided into four groups (n = 6 each): group I (immediate reperfusion), group II (simple cold storage in UWS), group III (hypothermic continuous coronary microperfusion with UWS), and group IV (hypothermic continuous coronary microperfusion with oxygenated UWS). Hearts in groups II, III, and IV were preserved for 24 hours. Preischemic and postischemic cardiac function was measured using a Langendorff apparatus. RESULTS: Hearts in group I showed complete functional recovery, whereas cardiac output in group II was inadequate. In groups III and IV, the percentage recovery rate (post/pre) of cardiac output was 57.0% +/- 3.1% and 82.2% +/- 9.1%, respectively (p < 0.05). In groups III and IV, perfusion pressures at the end of 24-hour preservation increased from the initial 5 mm Hg to 12.3 +/- 2.7 and 8.3 +/- 1.4 mm Hg (p < 0.05), respectively. In groups I, III, and IV, the percentage tissue water content was 82.8 +/- 1.0, 86.7 +/- 1.7, and 83.8 +/- 1.6, respectively (p < 0.05 for group III versus groups I and IV). There was a significant correlation between the percentage tissue water content and coronary perfusion pressure at the end of the 24-hour preservation (r = 0.60, p = 0.040) and a significant inverse correlation between percentage tissue water content and percentage recovery rate of cardiac output (r = -0.69, p = 0.014). In ultrastructural examination, myocardial tissue edema was limited and mitochondria were well preserved in group IV. CONCLUSION: We conclude that the combination of a hypothermic continuous coronary microperfusion technique and oxygenation of UWS was the procedure of choice for reducing tissue edema and improving both the coronary microcirculation and functional recovery during 24-hour heart preservation.

Adenosine↗

Effects of fibrin on the secretion of plasminogen activator inhibitor-1 from endothelial cells and on protein kinase C.

We previously demonstrated that cultured human umbilical vein endothelial cells (HUVECs) overlaid with a fibrin clot induced a slight increase in tissue-type plasminogen activator (t-PA) secretion and marked reduction in plasminogen activator inhibitor-1 (PAI-1) secretion. In this study, the intracellular signal transduction after fibrin stimulation was further investigated by analyzing cyclic AMP (cAMP) and protein kinase C (PK-C). When HUVECs were stimulated by fibrin clots, t-PA mRNA increased to 130% but PAI-1 mRNA decreased to 42%. These changes concurred with the data on the protein levels of t-PA and PAI-1 as previously reported. The effect of fibrin on t-PA production in HUVECs was not significantly altered after the elevation of cAMP by either forskolin or dibutyryl cAMP. Furthermore, an effect of fibrin on t-PA production did not appear when the cells were treated by phorbol 12-myristate 13-acetate (PMA) or 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H-7). The suppressive effect of fibrin on PAI-1 secretion from HUVECs was not altered by elevation of cAMP. Regarding the activation of PK-C by PMA, PAI-1 secretion was enhanced, but was suppressed by fibrin stimulation. H-7 suppressed PAI-1 secretion and further stimulation by fibrin almost completely abolished PAI-1 secretion. These changes were well associated with mRNA levels of t-PA and PAI-1. These results suggested that fibrin on HUVECs preferably down-regulates PK-C resulting in a decrease of PAI-1 in both the protein and mRNA levels and that effect of fibrin on t-PA secretion is neither involved in PK-C nor cAMP pathway.

Cells, Cultured↗

Neutrophil elastase inhibitor reduces asthmatic responses in allergic sheep.

To determine the role of neutrophil elastase in asthmatic responses, we studied the effect of ONO-5046, a specific neutrophil elastase inhibitor, on antigen-induced asthmatic responses in allergic sheep. Pulmonary resistance (RL) was measured for 8 h after antigen challenge. Measurements of airway responsiveness to methacholine and bronchoalveolar lavage fluid (BALF) were obtained 8 h after challenge. Antigen challenge caused early and late increases in RL, airway hyperresponsiveness (AHR), and recruitment of neutrophils and eosinophils along with increases in TXB2 and LTB4 in BALF. ONO-5046 treatment significantly reduced both early and late bronchoconstriction, neutrophil recruitment, increases in LTB4 in BALF, and AHR. ONO-5046 post-treatment significantly reduced the increase in RL 8 h after antigen challenge. Another neutrophil elastase inhibitor, FR 134043, significantly reduced both early and late bronchoconstriction. ONO-5046 had little effect on calcium ionophore-induced LTB4 release from isolated neutrophils and whole blood obtained from drug-treated sheep. These findings suggest that neutrophil elastase is involved in antigen-induced bronchoconstriction and AHR mediated by neutrophil accumulation and 5-lipoxygenase products in allergic sheep.

Airway Resistance↗

Expression of gamma delta T cell receptor on caprine globule leukocytes.

Histochemical characteristics and immunological surface phenotypes of globule leukocytes (GLs) of normal goats were investigated in the intestine. In the small intestine, GLs were concentrated in the base of the villus and around the crypt, whereas in the cecum and colon they were randomly distributed. Their cytoplasmic granules exclusively stained with phosphotungstic acid hematoxylin, and were negative for peroxidase and histamine in contrast to those of subepithelial mast cells. The existence of chondroitin sulfate in some granules of GLs and heparin in most granules of mast cells were revealed by alcian blue staining and digestion with chondroitinase ABC. Isolated intestinal GLs were positive for T cell receptor (TcR) 1-N24 (gamma delta) and CD8 alpha, and negative for WC1-N3 and WC1-N4. Cryostat sections of ileum revealed preferential intraepithelial distribution of both TcR1-N24+ cells and CD8+ cells. WC1-N3+ and WC1-N4+ cells were rarely seen in the epithelium and lamina propria. These results indicate that caprine GLs are a gamma delta T cell subset, which is a different cell population from WC1 positive gamma delta T cells.

Animals↗

Effects of subchronic treatments with SM-9018, a novel 5-HT2 and D2 antagonist, on dopamine and 5-HT receptors in rats.

1. Receptor binding and behavioral studies were performed to compare the effects of subchronic treatments with SM-9018, a novel 5-HT2 and D2 antagonist, and with haloperidol (HAL) on dopamine and 5-HT receptors in rats. 2. SM-9018 treatment (10 mg/kg/day p.o.) for 2 weeks did not significantly change the density (Bmax) of striatal D2 receptors or the incidence of stereotyped behavior induced by apomorphine (APO). By contrast, HAL treatment (3 mg/kg/day p.o., for 2 weeks) significantly increased the D2 receptor density by about 55% and markedly enhanced the behavioral response to APO. 3. The density of 5-HT2 receptors in the cerebral cortex was significantly reduced (about 20%) by SM-9018 treatment without being affected by HAL. However, the hyperthermic response of rats to p-chloroamphetamine (p-CAMP, a putative 5-HT releaser) was unaltered by either treatment. 4. Neither SM-9018 nor HAL treatment changed the density of 5-HT1A receptors in the hippocampus. 5. These findings suggest that SM-9018 is weaker than HAL in inducing up-regulation and supersensitivity of the striatal D2 receptors after the subchronic treatment.

Animals↗

Direct effect of cadmium on citrate uptake by isolated rat renal brush border membrane vesicles.

High incidence of multiple kidney stone formation has been observed among workers exposed to cadmium (Cd). Citrate is known to be a protective factor against renal stone formation. To study the direct effect of cadmium on citrate uptake by the renal brush border membrane, we exposed isolated rat renal brush border membrane vesicles (BBMV) to cadmium and determined their citrate uptake characteristics. BBMV were prepared by the divalent cation precipitation method. Citrate uptake was measured by the Millipore rapid membrane filtration technique. Preincubation of BBMV with 2 and 10 mM CdCl2 for 1 min significantly inhibited citrate uptake compared with that of BBMV without Cd. Analysis of the time course of citrate uptake during 30-min preincubation of BBMV with 0.5 mM Cd also revealed significant reduction of the uptake compared with that of the control BBMV without preincubation. These findings indicate that preincubation of BBMV with cadmium results in time-dependent and concentration-dependent inhibition of citrate uptake.

Animals↗

Endothelin receptor antagonists in a beagle model of pulmonary hypertension: contribution to possible potential therapy?

OBJECTIVES: This study investigated the pharmacologic effect of endothelin receptor antagonists on cardiopulmonary hemodynamic variables in a beagle model of pulmonary hypertension. BACKGROUND: We recently developed a beagle model of pulmonary hypertension that allows accurate determination of cardiopulmonary hemodynamic variables and is associated with elevated plasma endothelin-1 concentrations similar to those in pulmonary hypertension in humans. METHODS: Twelve beagles (pulmonary hypertension, n = 6; control group, n = 6) were studied during baseline conditions and during right atrial infusion of FR139317 (an ETA receptor antagonist), RES-701-1 (an ETB receptor antagonist), nitroglycerin and prostaglandin E1. Pulmonary hypertension was induced in experimental beagles 8 weeks after injection with 3 mg/kg body weight of dehydromonocrotaline. RESULTS: FR139317 lowered pulmonary artery and systemic arterial pressures in both pulmonary hypertensive and control beagles, with a significantly greater effect on pulmonary artery pressure in pulmonary hypertensive dogs. RES-701-1 tended to increase pulmonary artery pressure only in pulmonary hypertensive beagles. Nitroglycerin depressed pulmonary artery and systemic arterial tone equally well in control and pulmonary hypertensive animals. Prostaglandin E1 produced a greater decrease in systemic arterial pressure in pulmonary hypertensive than in normal beagles despite having the same effect on pulmonary artery pressure in both. CONCLUSIONS: ETA receptor antagonists decrease pulmonary artery pressure in a beagle model and may therefore be clinically useful for treatment of pulmonary hypertension.

Alprostadil↗

Disaccharide analysis of the skin glycosaminoglycans in chronically ultraviolet light-irradiated hairless mice.

The alteration of main disaccharide units in the skin of hairless mice (HOS:Hr 1) after chronic and repeated ultraviolet light (UV) radiation was investigated using high performance liquid chromatography after labeling with 1-phenyl-3-methyl-5-pyrazolone. The total amount of main disaccharide units increased by UVA irradiation at the 24th and 36th weeks in comparison with the control. At the 36th week UVA significantly increased hyaluronic acid-derived delta Di-HA (HA). Dermatan sulfate-derived delta Di 4S (DS) and chondroitin sulfate-derived delta Di-4S (CS) increased at the 36th week, although not statistically significant. The total amount of main disaccharide units was increased significantly by UVB irradiation at the 24th week as compared with the control. Concerning the compositional change in main disaccharide units after a 36-week repeated exposure, the decrease in delta Di-HA(HA) and the increase in delta Di-4S (DS) were found in the order of control, UVA- and UVB-irradiated groups. These results, for the first time, indicate the precise alterations of glycosaminoglycans, both in the total amount and in the composition, confirming the previous histochemical findings. This disaccharide analysis should provide a useful method to examine the biochemical changes of skin glycosaminoglycans in photoaging.

Animals↗

What factors affect ventricular performance after a Fontan-type operation?

Postoperative conditions after a Fontan-type operation, particularly as they affect results in the early term, are thought to depend on factors such as the state of pulmonary circulation and ventricular function. In this study, we attempted to determine the factors that influence ventricular characteristics in the middle term after Fontan-type procedures. Catheterization was performed at a mean of 15 months after operation in 57 patients with univentricular atrioventricular connection who underwent the operation between 1.0 and 22.6 years of age. End-diastolic volume, end-systolic volume, ejection fraction, and end-diastolic pressure of the systemic ventricle were analyzed together with an estimation of the systemic flow index. These parameters were influenced significantly by the presence of atrioventricular valve insufficiency. The morphologically left ventricle showed a better ejection fraction than did the morphologically right ventricle, whereas the systemic flow index was greater in patients undergoing total cavopulmonary connection than in those receiving an atriopulmonary connection. Young age was significantly associated with a better postoperative contractility, whereas the potential for impaired ventricular compliance was suggested in several patients undergoing operation after 4 years of age. On the basis of our results, we conclude that total cavopulmonary connection performed at a young age should be the surgical procedure of choice and that atrioventricular insufficiency must be treated properly at, and even after, the initial definitive repair.

Adolescent↗

Evaluation of two assay kits for thermostable direct hemolysin (TDH) as an indicator of TDH-related hemolysin (TRH) produced by Vibrio parahaemolyticus.

Reversed passive latex agglutination (RPLA) or enzyme-linked immunosorbent assay kits with beads (Bead-ELISA) are commercially available in Japan to detect the thermostable direct hemolysin (TDH) produced by Vibrio parahaemolyticus isolates. We evaluated whether these kits can be used to assay the pathogenic toxin, TDH-related hemolysin (TRH), produced by some so-called Kanagawa phenomenon-negative V. parahaemolyticus strains isolated from patients with diarrhea. Our results showed that the two kits, RPLA and Bead-ELISA, can detect TRH, although they were originally developed for detection of TDH. This may be due to the use of polyclonal anti-TDH antisera that cross react with TRH. Although the sensitivity for TDH detection by RPLA and Bead-ELISA differed tenfold, that for TRH detection was essentially equal. The minimum concentration of TRH required for detection by the two assay kits was about 10 ng/ml.

Enzyme Stability↗