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Biomedical subjects

K Asano

Publications and source records attributed to K Asano.

At least 271 records · Page 15Linked to original sources
PubMed1993

Anti-allergic activity of roxithromycin: inhibition of interleukin-5 production from mouse T lymphocytes.

This study was designed to evaluate the effects of roxithromycin (RXM), a newly synthesized macrolide antibiotic on allergic responses in mice. RXM was orally administered into BALB/c mice once a day for 42 days in a single dose of 5 mg/kg body weight. Spleen cells (Sp C) collected from mice on day 7, 14, 28 and 42 post-RXM administration showed higher blastic activity of lymphocytes than those from control. The activity peaked on the 7th day, then gradually decreased, and returned to the control level by the 42nd day. Production of cytokines, IL-2 and IL-5, by Sp C in response to concanavalin A stimulation was also examined in the course of RXM administration. The capacity of Sp C to produce IL-2 was enhanced by oral administration of RXM for 28 days. However, a long-term (for 42 days) administration inhibited it. On the other hand, the capacity of of Sp C to produce IL-5 was strongly inhibited by oral administration of RXM; the titer of IL-5 was similar to that obtained in cultures of Sp C from control mice. These results strongly suggest that oral administration of RXM inhibits the function of Th2-type helper T lymphocytes and that a long-term administration of RXM may be beneficial in asthma and allergy.

Animals↗
PubMed1993

Inhibitory action of azelastine on cytokine production from human peripheral blood leukocytes in vitro.

Effects of azelastine (AZ) on human peripheral blood leukocytes (PBL) in culture were examined. Addition of 10.0 micrograms/ml of AZ resulted in a marked inhibition of PBL blastic activity, but lower concentrations (1.0 and 0.5 microgram/ml) had no demonstrable suppressive effects on the activation. Interleukin (IL)-2, IL-3 and IL-4 production from PBL in response to Concanavalin A stimulation was also strongly suppressed when the cells were cultured in the presence of AZ. This suppression was observed even when lower concentrations (1.0 and 0.5 microgram/ml) of AZ were added to cell cultures.

Adult↗
PubMed1993

Anti-HIV (human immunodeficiency virus) activity of sulfated paramylon.

Sulfated derivatives of paramylon, a water-insoluble (1-3)-beta-D-glucan from Euglena gracilis, significantly inhibited the cytopathic effect of human immunodeficiency virus (HIV-1, HIV-2) and the expression of HIV antigen in cultured MT-4, MOLT-4 cells and human peripheral blood mononuclear cells. Native paramylon, N,N-dimethylaminoethyl paramylon, N,N-diethylaminoethyl paramylon, 2-hydroxy-3-trimethylammoniopropyl paramylon chloride, and carboxymethyl paramylon had little or no anti-HIV activity. The anti-HIV activity of the sulfated paramylon derivatives depended on the number of sulfate groups, and the molecular weight. Paramylon sulfate significantly inhibited HIV-1 binding to MT-4 cells. The anti-coagulant activity of the sulfated paramylon derivatives also depended on the number of sulfate groups, but was generally lower than that of dextran sulfate. The results point to the potential of paramylon sulfate in the treatment of HIV infection.

Animals↗
PubMed1993

Results of cesium needle interstitial implantation for carcinoma of the oral tongue.

One hundred thirty previously untreated patients with invasive squamous cell carcinoma of the oral tongue received interstitial radiotherapy with curative intent using cesium needles. Ninety-nine patients were treated with interstitial radiotherapy alone and 31 patients received interstitial radiotherapy combined with external beam irradiation. The recurrence-free rates in the primary lesions were 94.4% (17/18) in T1, 91.2% (52/57) in T2, and 70.9% (22/31) in T3 lesions. The local recurrence-free rates with single-plane and two-plane implantation were good: 89.7% (70/78) and 85.7% (12/14), respectively. The rate of 64.2% (9/14) for volume implantation was significantly poorer (p < 0.05). It is evident that tumor volume is an important factor in the control of cancer following interstitial therapy. The overall incidence of ulceration of the tongue and mandibular complication was 20% (26/130) and 13% (17/130), respectively. Using both interstitial and external radiotherapy, the incidence was 22.5%, compared with 10.1% using interstitial radiotherapy alone. The mandibular complication incidence of 8.9% with single-plane implants was much lower than 20.8% for two-plane and 23.5% for volume implants. Interstitial radiotherapy is most suitable in T1 and T2 cases in which single-plane implantation is possible; for these patients interstitial radiotherapy, which has the advantage of preserving the structure and function of the tongue, should continue to be used in the future in spite of the progress in reconstructive surgery.

Adult↗
PubMed1993

Age dependency of mitochondrial DNA decrease differs in different tissues of rat.

Mitochondrial DNA contents were measured using non-radioactive DNA probes for specific mtDNA sequences. The nuclear repetitive DNA sequence, LINE, was used as an internal standard marker. Age-dependent decreases in the mtDNA/nucDNA ratio in rat hepatic cells were confirmed with this method and, furthermore, a similar decrease was found in cardiac muscles. On the other hand, in thigh skeletal muscles such a decrease was not observed, slight increases being rather found in 18- to 24-month-old rats. The possible relationship of the decrease in mtDNA and the mechanism underlying animal senescence was discussed.

Aging↗
PubMed1993

The role of OX22- helper T cells in protective immunity to reinfection with Taenia taeniaeformis in rats.

Spleen cells (SpC) and mesenteric lymph node cells (MLNC) from F344 donor rats actively immunized by oral inoculation with Taenia taeniaeformis eggs were syngeneically transferred into previously uninfected recipient rats by intravenous injection. Recipient rats were challenged with eggs after cell transfer. The degree of immunity was assessed by counting the number of growing metacestodes (MC) in the liver and compared with that in controls. Transfer of 2 x 10(8) SpC, obtained from donors immunized for ten or more (but not for three or five) days before cell transfer inhibited the establishment of most of MC. There were approximately 86-88% reductions in MC recoveries. SpC (2 x 10(8)) obtained from donors immunized for ten days inhibited the establishment of most of MC in recipient rats when transferred nought, two, or 24 h (but not 48 h) before egg challenge. Functional cells in the immune SpC were helper T cells W3/25+, OX8- and OX22-. However, immune MLNC obtained from donors immunized for three to ten days before cell transfer had no effect on transferring immunity.

Animals↗
PubMed1993

Quantitative structure-activity relationship (QSAR) study of elastase substrates and inhibitors.

One hundred Suc-X-Y-Ala-pNA peptides: (Suc: succinyl, pNA: p-nitroanilide, X, Y: Gly, Ala, Val, Leu, Ile, Phe, Pro, alpha-aminobutyric acid, norvaline, norleucine) were synthesized and their reaction constants with porcine pancreatic elastase (Km, kcat and kcat/Km) were determined. These reaction constants were quantitatively analyzed using the Free-Wilson/Fujita-Ban method. The contribution of amino acid side chains to the reaction constants Km, kcat and kcat/Km, expressed logarithmically, was found to be additive. On the other hand, 19 elastase inhibitors of the general formula CF3CO-X-Y-Ala-pNA (X,Y: ten amino acids) were synthesized, and their inhibition constants were compared with the Michaelis constant for the corresponding substrates and analyzed using free-energy-related substituent constants. In the analysis of amino acid side chains in the Y position, the Ki value of the inhibitor was generally correlated to the Km value of the substrate, which corresponded to the inhibitor, thus confirming the validity of the equation. log(1/Ki) = 1.271 log(1/Km) + 4.831 This study may serve as a prototypical approach to unraveling structure-activity relationships of peptide substrates and inhibitors of medicinal or agricultural importance.

Amino Acid Sequence↗
PubMed1993

Is an additional vaccination necessary for a successful second pregnancy in unexplained recurrent aborters who were successfully immunized with their husband's lymphocytes before the first pregnancy?

PROBLEM: Is an additional immunotherapy necessary or not for patients who have obtained successful results after initial immunotherapy? METHODS: The successive pregnancy outcome was analyzed in 22 patients out of 29 unexplained recurrent aborters who had undergone immunotherapy with their husband's lymphocytes according to our previously reported protocol (Takakuwa et al., Am J Reprod Immunol Microbiol. 10:1-9, 1986; Takakuwa et al., Am J Reprod Immunol. 23:37-41, 1990) and had obtained successful outcome between January 1983 and December 1989. In addition, the alteration of blocking antibodies (BAbs), which was evaluated by a one-way mixed lymphocyte culture reaction (MLR) blocking assay between the spouses, was analyzed in 26 patients out of 29. RESULTS: None of the 22 patients underwent further immunotherapy because a significantly high titer of MLR-BAbs had been detected before the new pregnancy. In 19 out of the 21 patients (90.5%), pregnancy was successful. CONCLUSION: Additional immunotherapy is not necessary for patients who have obtained successful results after the initial immunotherapy and are positive for MLR-BAbs after their first delivery.

Abortion, Habitual↗
PubMed1993

Time-dependently enhanced pressor responses in rat lungs after chronic exposure to high altitude.

To investigate the de-acclimatization process with respect to pulmonary vasoreactivity after high-altitude exposure, we performed a study of changes in pressor responses over time in salt-perfused lungs from rats that had been exposed to high altitude (HA, n = 41, 20 weeks at actual 2400 m). Comparisons were made with the lungs of rats kept at low altitude (n = 8, kept at 610 m). We studied HA rats from the time just after removal from high altitude to 2 weeks after the exposure. The pressor responses of HA lungs to both 0.5 microgram-angiotensin II and 5 min airway hypoxia (3% O2) just after the exposure did not differ from those of controls, but their responses began to increase within 12 h, and reached a maximum 3 days after exposure ended. The increase was time-dependent. We conclude that pulmonary vasopressor responses are enhanced time-dependently during the very early stages of de-acclimatization after high-altitude exposure.

Altitude↗
PubMed1993

Effects of pH and SO2 on solubility coefficients of inert gases in human whole blood.

We systematically investigated the quantitative importance of pH and O2 saturation (SO2) of hemoglobin on the solubility coefficients (alpha) for six inert gases: sulfur hexafluoride, N2, ethane, cyclopropane, halothane, and diethyl ether. Measurements of alpha were made at 37 degrees C with SO2 of 0-1.0 and pH of 7.2-7.7 by use of whole blood obtained from three healthy subjects. No significant dependence of alpha on pH was demonstrated for sulfur hexafluoride, N2, halothane, or diethyl ether, but an appreciable augmentation of alpha with increasing pH was found for ethane and cyclopropane. No alpha value obtained for oxygenated blood differed statistically from that for deoxygenated blood. In addition to the basic findings on the effects of pH on alpha values of ethane and cyclopropane with the multiple inert gas elimination technique (data obtained from 22 patients with either interstitial pneumonia or chronic obstructive pulmonary disease), we also found that dependence of alpha on blood pH exerted no significant influence on the recovery of ventilation-perfusion distribution in the lung. We concluded that: 1) pH plays an appreciable role in determining gas solubilities in blood, 2) SO2 is not a decisive factor for gas solubilities in blood, and 3) the influence of various pH values in pulmonary capillaries on inert gas exchange is negligible.

Adult↗
PubMed1993

[Effect of Y-25130, a selective 5-HT3 receptor antagonist, on the intestinal fluid secretion in rats].

We studied the effect of Y-25130 on the intestinal fluid secretion induced by 5-HT and cholera toxin in rats. 1) Net fluid secretion was increased dose-dependently by intramesenteric artery infusion of 5-HT (1-10 micrograms/min). 2) Y-25130 (0.01-1 mg/kg, i.v.) inhibited the net fluid secretion induced by 5-HT (3 micrograms/min). Granisetron and ondansetron also inhibited the net fluid secretion induced by 5-HT. 3) Methysergide did not inhibit the fluid secretion, and neither atropine nor tetrodotoxin inhibited it. 4) Cholera toxin (1-10 micrograms/2 ml into jejunal loops) caused profuse net fluid secretion. 5) Y-25130 (1 mg/kg, i.v.) inhibited the net fluid secretion induced by cholera toxin (3 micrograms/2 ml). Granisetron was inhibitory and ondansetron tended to inhibit the cholera toxin-induced secretion. These results suggest that 5-HT may increase the net fluid secretion through 5-HT3 receptors, and cholera toxin-induced fluid secretion may be at least partially mediated by 5-HT3 receptors. It is expected that Y-25130 may be useful for treating secretory diarrhea in humans.

Animals↗
PubMed1993

Sleep and respiration under acute hypobaric hypoxia.

The purpose of this study was to elucidate the effects of acute hypobaric hypoxia on nocturnal sleep architecture and respiratory responses in a hypobaric simulator. Five healthy young males (19-23 years old) were recruited to sleep for 8 h at sea level and at simulated altitudes of 1,500, 3,000, and 4,000 m in the simulator (61.2 m3, 20 degrees C, and 60% RH). Each experimental run was separated by at least 3 d. Standard polysomnograph, respiration, and arterial oxygen saturation (SaO2) during sleep were observed. 1) SaO2 decreased significantly with increasing altitude. At 4,000 m, SaO2 showed its lowest value during 1 to 3 h after sleep onset. 2) Sleep architecture below 3,000 m showed almost the same pattern. However, reduction in REM sleep and increased wakefulness were observed at 4,000 m, though such sleep disturbance was not observed in the first one-third of the night spent in bed. 3) Periodic breathing (PB) with apnea and/or hypopnea developed in all subjects above 3,000 m. PB tended to appear in light sleep, though sleep was not always disturbed by PB. It might be concluded that there was no sleep disturbance up to 3,000 m altitude. Nocturnal sleep at 4,000 m, however, was disturbed after a few hours from sleep onset by severe hypoxemia induced by multiplicative effects of hypoxia and hypoventilation during deep sleep. At high altitude, PB seems to not induce arousals consistently, which was different from sleep apnea syndrome at sea level.

Adult↗
PubMed1993

Transport of Na+ and HCO3- out of red blood cells is simultaneous with a chloride shift in canine and human whole blood exposed to CO2-rich gas.

To study the release of Na+ from erythrocytes, arterial whole blood obtained from anesthetized and heparinized dogs (n = 8), or human (n = 9) venous blood was aerated with a CO2-rich gas mixture (15% CO2, 25% O2, 60% N2) at a rate of 1 l/min. To examine possible mechanisms involved in the release of sodium ions into plasma, CO2-rich gas was also passed through whole blood in the presence of acetazolamide (n = 8), SITS (n = 8), or furosemide (n = 8). The changes in blood gas parameters, plasma protein concentration, hematocrit, and plasma sodium, chloride, and bicarbonate ion concentrations were examined. When CO2-rich gas was passed through treated and untreated canine or human whole blood, PCO2 and plasma sodium and bicarbonate contents per ml of blood increased, while pH and plasma chloride content per ml of whole blood decreased. After 0 to 5 min of CO2-rich gassing, the mean rates of change in plasma ion contents per ml of whole blood per min were related by the following equations: (1) delta MCI- = a (delta MNa+), (2) delta MHCO3- = b(delta MNa+), (3) delta MHCO3- approximately equal to delta MNa+ + delta MCl-, (4) b approximately equal to 1 + a. These results suggest that the release of Na+ and HCO3- from erythrocytes into plasma in canine and human whole blood occurred in a one-to-one ratio simultaneously with, and probably independently of, the well-known chloride shift during a period of 0 to 5 min after the start of CO2-rich gassing.

4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfo↗
PubMed1993

[Chemotherapy of malignant melanoma].

Malignant melanoma is among the malignant tumors which still have the poorest prognosis. Thus, malignant melanoma of stage II and the more advanced stages. At present, chemotherapeutic combinations used as the first choice in Japan are two regimens of postoperative adjuvant therapy for stage II and III patients, that aim at preventing recurrence. One of the regimens is a DAV combination (Dacarbazine, ACNU, vincristine), and another is PAV combination (Pepleomycin, ACNU, vincristine). For stage IV patients, the major therapeutic procedure is a CDV combination (cisplatin, dacarbazine, vindesine). The efficacy of CDV treatment has been approximately 30 per cent in our studies. It has shown comparable effects for metastatic lesion in the lymph nodes, mucous membrane (nasal cavity) and brain, while lesions in other organs are largely unaffected in many instances. Studies of new drugs and combinations must be undertaken for the treatment of malignant melanoma.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

[Application of lactate threshold in the exercise program for patients with coronary heart disease].

This study was conducted 1) to measure the exercise intensity corresponding to lactate threshold (LT) and 2) to clarify the method of prescribing LT level for patients with coronary heart disease (CHD) on the assumption that LT level indicates an optimal exercise intensity for those patients. Three males and 9 females with CHD, aged 57.6 +/- 7.7, participated in this study. Oxygen uptake (VO2), heart rate (HR), and ratings of perceived exertion (RPE) at LT and at maximal exercise were measured before (pre), 4 months (mid) and 8 months (post) after exercise conditioning. The intensity of most exercises was maintained at the level of LT. A significant increase was found in VO2LT from pre- to mid-test, and further increase was found from mid- to post-test after matching exercise intensity to the improvement in VO2LT. It is suggested that matching the progression of the absolute exercise intensity with the training-induced improvements of aerobic capacity i.e., maintaining the exercise intensity at LT for a sustained period of time, is a valid procedure for further improvement in aerobic capacity of CHD patients.

Aged↗
PubMed1993

[Roles of serotonin in glass-bead pulmonary microemboli].

We investigated the role of serotonin release from aggregating platelets in glass-bead microemboli on isolated perfused rabbit lungs. The perfusion was performed at 70 ml/min with a roller pump. The temperature of the perfusion circuit was maintained at 37 +/- 1 degrees C by means of a heat exchanger. 100 microns-diameter glass beads (1 g) were infused via the main pulmonary artery. We examined the concentration of serotonin and the number of platelets in the perfusate and the mean pulmonary arterial pressure before and after glass bead embolization. Administration of PRP (platelet-rich plasma) to the perfusate caused the concentration of serotonin to significantly increase after microembolization. Specific serotonin S2 receptor antagonist (DV-7028) inhibited the increase of serotonin concentration in the perfusate, platelet aggregation, and vasoconstriction. We concluded that in the glass-bead embolization model, serotonin was released from aggregating platelets surrounding the glass beads, and constricted pulmonary microvessels via serotonin S2 receptors on the vascular smooth muscles cells.

Animals↗
PubMed1993

[Effect of diffusion limitation on gas exchange in the lung--analysis in oleic acid-induced lung injury].

To assess the effect of diffusion limitation on gas exchange in injured lungs with non-cardiogenic pulmonary edema, an experimental model of acute lung injury with alveolar flooding was produced in six mongrel dogs by intravenously injecting oleic acid at 0.06 ml/kg. The effect of diffusion limitation was quantitatively examined by measuring the excretion (E) of three indicator gases (acetylene, ethylene and freon-22) with differing solubility (lambda) and tissue diffusivity (d). The indicator gases were dissolved in normal saline and infused at a constant rate through a peripheral vein. Since acetylene and ethylene have nearly identical of d but differing lambda, the difference in E values of these two gases may solely reflect the effect of uneven distribution of ventilation-perfusion ratios (VA/Q) in the lung. Thus, measured E values of acetylene and ethylene allowed us to approximately predict the E of freon-22, the value corresponding to the condition where d of freon-22 was taken to be equal to that of acetylene or ethylene. The difference between predicted and measured E values of freon-22 is indicative of the limitation of diffusion in the lung periphery. In all the lungs studied, measured E values of freon-22 were consistently smaller than those predicted from acetylene and ethylene, leading to the conclusion that gas exchange in injured lungs with widespread pulmonary edema was partly impaired by diffusion in aqueous media.

Animals↗