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M Kondo

Publications and source records attributed to M Kondo.

At least 685 records · Page 38Linked to original sources

Analysis of longitudinal distribution of pulmonary vascular resistance by use of a five element lumped model.

To analyze longitudinal distribution of pulmonary vascular resistance, we proposed a five element lumped model which partitioned pulmonary circulation into pulmonary arterial, middle and pulmonary venous segment. The validity and anatomical correlation of the model were tested in an isolated, perfused, canine lung lobe preparation with inflow/outflow occlusion techniques. With arterial occlusion, pulmonary arterial pressure fell rapidly and then exponentially. With venous occlusion, pulmonary venous pressure rose suddenly and then exponentially. Theoretical pressure profiles produced by computer simulation of the model well approximated the general characteristics of the experimental traces. Serotonin increased the pressure gradient across the pulmonary arterial segment (delta Pa), whereas histamine increased the gradient across the pulmonary venous segment (delta Pv). Neither drug altered the gradient across the middle segment (delta Pm). The results suggest that the lumped model is a useful concept to understand the longitudinal distribution of pulmonary vascular resistance, and that delta Pa, delta Pm and delta Pv reflect the resistance distribution of anatomical pulmonary arteries, alveolar vessels and pulmonary veins, respectively.

Animals↗

Cardiovascular effects of dibutyryl cyclic AMP and milrinone under right heart bypass in anesthetized dogs.

To compare the cardiovascular effects of dibutyryl cyclic AMP (DBcAMP) and milrinone, we used the right heart bypass method in intact anesthetized dogs. The preload of the left ventricle was maintained constant throughout the experiment. Therefore, the effects of DBcAMP and milrinone on cardiac contractility and afterload of the left ventricle were investigated respectively without preload influence. DBcAMP and milrinone exhibited marked positive chronotropic-, positive inotropic-, vasodilative- and diuretic-activity. DBcAMP expressed these effects gradually and continuously, whereas milrinone expressed its pharmacological actions rapidly, but for a short duration of time. Both the afterload-reducing and the cardiac contractile force-enhancing activities of DBcAMP were longer lasting than those of milrinone. Mean arterial pressure was not altered by DBcAMP infusion, whereas it was increased significantly (p < 0.05) by milrinone infusion. The results of this study suggested that DBcAMP appeared to be indicated when there is a need to increase cardiac output by reducing afterload and increasing cardiac contractile force gradually and continuously. On the other hand, milrinone would seem to be indicated when the goal is to raise blood pressure rapidly and to increase cardiac output simultaneously.

Animals↗

Effect of CL 316,243, a novel beta 3-adrenoceptor agonist, on insulin secretion in perfused mouse pancreas.

In order to clarify the insulin-release mechanism of beta 3-adrenoceptor agonist, we examined the effect of CL 316,243, a highly specific beta 3-adrenoceptor agonist having a relative potency of beta 1:beta 2:beta 3 = 0:1:100,000, on insulin secretion in perfused mouse pancreas. The application of 0.2 mM and 0.5 mM CL 316,243 produced significant insulin secretion from within 1 min, which lasted until 2 min after its withdrawal. DL-propranolol and ICI 118551 at 0.2 mM partially inhibited the insulin secretion induced by the 0.2 mM CL 316,243, but 0.2 mM metoprolol had no effect on the insulin release produced by 0.2 mM CL 316,243. We conclude that beta 3-adrenoceptor agonist stimulates insulin secretion via beta 3-action in the perfused mouse pancreas.

Adrenergic beta-Agonists↗

Anti-obesity effect of CL 316,243, a highly specific beta 3-adrenoceptor agonist, in mice with monosodium-L-glutamate-induced obesity.

The effects of CL 316,243, a highly specific beta 3-adrenoceptor agonist (relative selectivities of 0, 1 and 100,000 for beta 1-, beta 2- and beta 3-receptors, respectively), were evaluated in mice with monosodium L-glutamate (MSG)-induced obesity as well as in control mice injected with physiological saline instead of MSG. Both MSG- and saline-treated mice were divided into three groups and at 8 weeks of age received either CL 316,243 (0.1 or 1.0 mg/kg) or distilled water through a gastric tube for 2 weeks. CL 316,243 not only reduced white adipose tissue mass but also activated brown adipose tissue and systemic metabolism, and hence reduced body mass without affecting food intake. Furthermore, CL 316,243 decreased hyperglycemia and hypertriglyceridemia in MSG-treated mice. However, at the higher dose, CL 316,243 also increased liver triglyceride in MSG-treated mice. These observations suggest that CL 316,243 exerts an anti-obesity effect in mice with MSG-induced obesity and consequently may prove efficacious in the treatment of human obesity.

Adrenergic beta-Agonists↗

Survey of fluctuating fetal body weights in Sprague-Dawley rats.

During the past 9 years of reproductive and developmental toxicity studies in Sprague-Dawley rat, we noticed that the average fetal body weight on day 20 of gestation in 81 control groups fluctuated significantly from study to study. The other parameters such as number of implants, resorption rats and number of live fetuses were relatively stable. With information cooperatively given by the animal supplier, we could pin down the possibility of the fluctuation. The animal supplier introduced Sprague-Dawley rats into Japan from the U. S. twice in the past. The documents we analyzed indicated that the fluctuation in fetal body weight was caused by different two colonies which were introduced into Japan at the different times.

Animals↗

Movement of carboxyfluorescein across the isolated rabbit iris-ciliary body.

The movement of carboxyfluorescein across the isolated iris-ciliary body of the albino rabbit was analyzed using an Ussing chamber under short-circuit conditions with carboxyfluorescein concentrations ranging from 10 to 100 microM. At a concentration of 50 microM, the outward permeability (from the aqueous to the stromal side) was 4.0 +/- 0.2 x 10(-6) cm/sec and the inward permeability (from the stromal to the aqueous side) was 1.3 +/- 0.2 x 10(-6) cm/sec (Mean +/- SE, N = 6). The former was significantly greater than the latter (P < 0.001). Inward movement of carboxyfluorescein showed a linear increase in relation to the concentrations tested. Neither ouabain (100 microM), 2,4-dinitrophenol (10 microM) nor probenecid (100 microM) significantly inhibited the inward movement of carboxyfluorescein. The net outward movement of carboxy-fluorescein became saturated, as concentration was increased, and a Lineweaver--Burke plot gave an apparent Km of 28 microM and Vmax of 0.67 x 10(-9) mole/hr/cm2. In addition, outward carboxyfluorescein movement was significantly inhibited by ouabain (100 microM), 2,4-dinitrophenol (10 microM), probenecid (100 microM), iodipamide (1.0 mM), hippurate (1.0 mM), low temperature or low external Na+ concentration. These results suggest that outward carboxyfluorescein movement across the tissue largely depends on carrier-mediated active transport, while inward movement occurs by passive diffusion.

Animals↗

Antioxidative effects of a processed grain food.

Antioxidant biofactor: AOB is a unique processed grain food. It is a yellow-green powder. It contains the following extracts: germ extracts, soybean, rice bran, tear grass, sesame, wheat, citron, green tea, green leaf extract, and malted rice. These materials were slowly roasted under a powdered oure at less than 60 degrees C and fermented with Aspergillus oryzae over 3 days to transform each ingredient into low molecular weight substances. These conditions were different by each material, environmental humidity and temperature. It probably contains a variety of substances having antioxidant activity including flavonoids, alpha-tocopherol, vitamin C, and tannins. We investigated its antioxidative properties using electron spin resonance (ESR) and autoxidation of rat brain homogenates. The superoxide, hydroxyl radical, and the stable free radical, diphenyl-p-picrylhydrazyl (DPPH) radical scavenging activity of AOB was investigated using ESR spectrometry. In an in vitro study, a suspension of AOB was added directly to a superoxide generating system (hypoxanthine-xanthine oxidase; HX/XO) and investigated using 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) as a spin trapping agent. At final concentrations of 0.01, 0.05, and 0.1 mg/ml, AOB dose-dependent scavenging activity was observed as 0.103, 0.619, and 1.369 U/ml, respectively. A concentration of 1.0 mg/ml completely scavenged DMPO-OOH signals; 1.0 mg/ml of AOB inhibited the DMPO-OH signal generated by Fenton's reaction, but its inhibitory effect was not competitive, and was inhibition of the Fenton's reaction. 1.0, 3.0, and 5.0 mg/ml of AOB were significantly inhibited the DPPH radical. In an in vivo study, rats were fed AOB orally at doses of 1 or 5 g/day for 24 h or for 3 days and the superoxide scavenging activity was measured in plasma. With the administration of 1 g/day for 3 days, the superoxide scavenging activity was about 1.8 times that of the control group fed a basal diet; 1.5 times the control with 5 g/day for 1 day, and 2.6 times the control with 5 g/day for 3 days, all of which represented significant increases in superoxide scavenging activity. AOB strongly inhibited the autoxidation of rat brain homogenates in vitro in a dose-dependent manner. However, each ingredient before roast and fermentation little inhibited lipid peroxidation. Roasting and fermentation with A. oryzae way be important to transform each ingredient into low molecular weight substances. Therefore, it was suggested that AOB possesses strong antioxidant and free radical scavenging activities.

Animals↗

The alpha/beta-adrenergic receptor blocker arotinolol activates the thermogenesis of brown adipose tissue in monosodium-L-glutamate-induced obese mice.

We have found previously that arotinolol, an alpha/beta-adrenergic blocker, increases blood flow in brown adipose tissue (BAT) in a similar extent as BRL 26830A, a beta 3-adrenoceptor agonist. We tested the hypothesis that arotinolol activates thermogenesis in BAT, leading to weight loss in monosodium-L-glutamate-induced (MSG-induced) obese mice and saline-treated controls. Six weeks of standard animal feed (CE-2) containing arotinolol hydrochloride (350 mg/kg CE-2), which reduced mean blood pressure in MSG-treated mice, significantly increased the mitochondrial protein content in BAT, and activated the specific and total binding of guanosine-5'-diphosphate (GDP) in BAT mitochondria, leading to a reduction of obesity in both MSG- and saline-treated mice vs. the control groups fed with CE-2 diet alone. However, six weeks of CE-2 diet containing propranolol hydrochloride (525 mg/kg CE-2) a non-selective beta-blocker, markedly reduced the specific and total binding of GDP in BAT mitochondria, leading to weight gain in both MSG- and saline-treated mice. These findings support the hypothesis, that arotinolol activates BAT thermogenesis, leading to weight loss.

Adipose Tissue↗

Usefulness of mazindol in combined diet therapy consisting of a low-calorie diet and Optifast in severely obese women.

We conducted a double-blind test to examine whether or not the addition of mazindol, an appetite suppressor, to combined diet therapy [low-calorie diet + Optifast: 4600-3928kj(1100-940 kcal)/day] enhances the weight-reduction effect and reduces dropout from treatment in women with severe obesity. All of the patients were enrolled in the combined diet therapy and exercise [1255kj(300 kcal/day)] for 7 months. At the end of the first month, the patients were given, at random, three tablets of either 0.5 mg mazindol (18 women) or placebo (18 women) per day, in three doses for three months, in addition to the diet and exercise therapies. At 7 months, the key for the double-blind test was opened by the controller. Four of the 18 patients in the placebo group dropped out of the programme at 2 months after drug treatment, because they could not endure the intense hunger. Therefore, data for these 4 patients were excluded from evaluation. However, none of the patients treated with mazindol + combined diet therapy dropped out. The body weight and body-fat ratio showed marked reduction (p < 0.01 vs. premedication weight). The percent weight loss and percent reduction in body-fat ratio in the mazindol group was significantly (p < 0.01) greater than those found in the placebo group, which also showed a significant decrease in body weight and body-fat ratio (p < 0.01 vs. pre-medication weight) during the same period.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Enterocolitis].

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Enterocolitis↗

[Cell-to-cell interaction in airway mucosa--effect of eosinophils on airway epithelial ion transport].

We examined the interaction between eosinophil-derived mediators and ion transport in airway epithelial cells. Eosinophils were obtained by peritoneal lavage from polymyxin B-treated guinea-pigs and were purified over discontinuous Percoll density gradients. The activated eosinophil supernatant was prepared with a two-stage method in the presence of A23187. The effects of eosinophil supernatant on the electric properties of cultured epithelial cells from cow trachea were examined in an Ussing chamber under short-circuit conditions. The eosinophil supernatant added to the serosal and mucosal sides increased the short-circuit current (Isc) in an eosinophil number-dependent manner (3 x 10(6), 10(7) eosinophils: delta Isc 9 +/- 1 microA/cm2, 18 +/- 3 microA/cm2). The response was inhibited by treatment of epithelial cells with diphenylamine-2-carboxylate but not by amiloride. The increase in Isc induced by the supermatant from eosinophils treated with indomethacin or the lipoxygenase inhibitor AA861 was significantly less than that induced by untreated eosinophils. These results indicate that activated eosinophils stimulate C1 secretion in airway epithelium via release of metabolites of arachidonic acid.

Animals↗

[Enterocolitis].

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Enterocolitis↗

[Pharmacokinetic and clinical studies of cefozopran in the field of pediatrics].

Pharmacokinetic and clinical studies on cefozopran (CZOP, SCE-2787), a new cephalosporin antibiotic, were carried out in the field of pediatrics. The results obtained are summarized below. 1. Serum concentrations and urinary excretion rates were determined after intravenous bolus injection of CZOP at a dose of 20 mg/kg for 5 minutes in 3 cases. The mean serum concentration of CZOP was 45.9 micrograms/ml at 30 minutes with the serum half-life of 1.77 hours. The mean cumulative urinary excretion rate in the first 8 hours after administration was 71.4%. 2. Fourteen patients with bacterial infections (pneumonia 9 cases, urinary tract infection 4 cases and lymphadenitis 1 case) were treated with CZOP at a daily dose of 55.8-65.7 mg/kg. The overall clinical efficacy and bacteriological eradication rates were both 100%. 3. No adverse reactions were observed. Abnormal laboratory test results were mild, slight elevation of GOT and GOT, GPT & LDH in 1 each and eosinophilia and thrombocytosis in 2 cases each.

Cephalosporins↗

[Continuous monitoring of nitric oxide release from airway mucosa].

There is increasing evidence that nitric oxide (NO) plays a role in the regulation of airway and vascular smooth muscle tone, pulmonary microvascular permeability, and host defense. However, it remains uncertain whether NO is actually released from airway mucosa. We therefore directly measured NO concentrations in the perfusate of rabbit tracheal mucosal surface, with an NO-selective electrode. The electrode was made of Pt/Ir alloy coated with a three-layered membrane that consisted of KCl, No-selective silicone resin, and a normal silicone membrane. Termination of tracheal perfusion with Krebs-Henseleit solution increased the electrical current derived from oxidation of NO at the electrode, and reperfusion rapidly decreased the current to the baseline value. Addition of L-NG-arginine methylester (L-NAME, 10(-3) M) to the perfusate decreased NO release, but D-NAME had no effect. Subsequent addition of L-arginine (10(-3) M) reversed the inhibition by L-NAME and greatly increased NO release above the baseline value. Histochemical staining to reveal NADPH diaphorase activity in the tracheal tissue showed a strong blue reaction mainly in the epithelial cells. These results suggest that NO is continuously released in the airway mucosal surface, probably from the epithelial cells rich in NO synthase.

Animals↗

Mechanism of anti-obesity action of benidipine hydrochloride in mice.

Benidipine hydrochloride, a dihydropyridine calcium antagonist, decreases body weight and also has a hypotensive effect. The mechanism of its inhibitory effect on body weight is unclear, although this agent increases blood flow in brown adipose tissue, which functions as a main thermogenic organ. The hypothesis that benidipine hydrochloride activates brown adipose tissue to induce body weight loss was tested on mice made obese by pretreatment with monosodium-L-glutamate (MSG). When benidipine hydrochloride was incorporated in the diet (1.0 mg per gram of food) for 4 weeks, binding of guanosine-5'-diphosphate in brown adipose tissue mitochondria was significantly increased. Body weight and body fat decreased in both MSG obese mice and in lean controls. Results support the hypothesis and suggest the possibility that benidipine hydrochloride may be useful for treating obese hypertensive patients.

Adipose Tissue, Brown↗

Parental origin of 11p15 deletions in human lung cancer.

Frequent occurrence of 11p deletions has been reported for diverse types of human cancers including lung cancers and Wilms' tumors. In contrast to the well documented identification of preferential retention of the paternal allele in Wilms' tumors, no data have hitherto been available for cancers of adults. Taking advantage of the paternal allele-specific expression of IGF2 in the normal lung, we examined 79 lung cancer cases to investigate allelic loss at 11p15 and the parental origin of the retained alleles. While 11 of 36 (31%) informative lung cancer cases exhibited 11p15 deletions, only seven of these (64%) retained the paternal allele in tumors (P = 0.274), showing a contrast to the strong paternal bias in childhood tumors. Our strategy eliminates the need for parental DNAs for the determination and should be applicable to other adulthood tumors carrying 11p deletions such as breast and bladder cancers.

Adult↗