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Biomedical subjects

T Aikawa

Publications and source records attributed to T Aikawa.

At least 109 records · Page 6Linked to original sources
PubMed1989

Effect of ursodeoxycholic acid in chronic hepatitis and primary biliary cirrhosis.

Clinical and experimental investigations have suggested that ursodeoxycholic acid (ursodiol) may have cytoprotective or choleretic action and therefore be beneficial in patients with intrahepatic cholestasis or chronic liver disease. In an open-label study, we treated 45 patients with chronic hepatitis with 300 mg of ursodiol three times daily for six months. At four months, gamma-glutamyl transpeptidase (gamma-GTP) and leucine aminopeptidase levels had decreased. SGOT and SGPT levels also decreased significantly. Evaluation of histologic changes has not yet been completed. No significant differences in improvement of liver function tests were found in a comparison with 19 historical controls. We also studied eight patients with primary biliary cirrhosis, treated for more than one and a half years with 600 mg of ursodiol per day. At one month, itching diminished in five patients who had pruritus. ALPase and gamma-GTP levels decreased significantly, and GOT and GPT levels were also reduced. IgM levels did not change, but the titer of antimitochondrial body decreased by half in two patients. Levels of glycoursodeoxycholic acid increased, and in three patients follow-up liver biopsy showed marked improvement. These preliminary results suggest that ursodiol is safe and effective for the treatment of chronic hepatitis and primary biliary cirrhosis, but a large-scale, controlled trial is needed.

Alanine Transaminase↗
PubMed1989

Preparation of a fine powder of 2-deoxy-2-[18F]fluoro-D-glucose suitable for inhalation to diagnose lung diseases by means of PET.

Fine 2-deoxy-2-[18F]fluoro-D-glucose (18FDG) powder was obtained by adding diethyl ether into a methyl alcohol solution of 18FDG and other sugar as seed. When micronized particles of sodium N-acetyl-neuraminate (Neu5Ac-Na) were used as seed crystals, particles containing 18FDG were obtained and 80% of them were smaller than 10 microns in size. More than 60% of these crystals were 4-6 microns in size. In a preclinical study of forced inhalation in a dog, the 18FDG fine powder was mainly distributed in the trachea. The radioactivity in the trachea then increased once and a gradual decrease followed. The radioactivity was transferred into the blood and radioactivity incorporation into the heart was observed. After a normal volunteer inhaled 18FDG dry powder aerosol, the radioactivity was found in the respiratory tract and the peripheral area of the lung by means of PET. Absorption and in vivo dynamics of the 18FDG were also analysed.

Administration, Inhalation↗
PubMed1989

Leukotriene C4 and B4 in bronchoalveolar lavage fluid during biphasic allergic bronchoconstriction in sheep.

To study the contribution of leukotriene C4 (LTC4), leukotriene D4 (LTD4), leukotriene B4 (LTB4), and inflammation to the antigen-induced late bronchial response, these leukotrienes, histamine, and cell differentials were evaluated in bronchoalveolar lavage fluid (BALF). Immediate and late responses were induced by Ascaris suum antigen inhalation in 11 conscious sheep. Bronchoalveolar lavage was performed on 3 separate test days, before challenge (control), during the immediate response, and during the late response. Leukotrienes were measured by radioimmunoassay after purification by reverse-phase high-performance liquid chromatography. LTB4 and LTC4 were detected in control BALF, but LTD4 was not. LTC4 and LTB4 were increased in the late response (p less than 0.05 compared with each control). The percent neutrophils recovered by bronchoalveolar lavage was increased during the late response, and this was significantly correlated with pulmonary resistance (p less than 0.01). Histamine levels in BALF were elevated during the immediate response but not during the late response. Our results suggest that histamine and LTC4 may contribute to the contraction of bronchial smooth muscle in the immediate and the late response, respectively. The increase in LTB4, a neutrophil chemotactic factor, during the late response may be responsible for the increase in the percent neutrophils.

Administration, Inhalation↗
PubMed1989

Morphometric analysis of intraluminal mucus in airways in chronic obstructive pulmonary disease.

Mucus volume in both central and peripheral airways was assessed in 13 patients, six with chronic bronchitis (CB) and seven with chronic pulmonary emphysema (CPE), by morphologic quantitative measurement in autopsied lungs, and the results were compared with those from four control lungs (NL). The patients with CB and CPE had severe obstructive impairment that did not differ significantly between the two groups (FEV1%, mean 45% in CB and mean 49% in CPE). Mucous hypersecretion during clinical remission differed significantly between the CB and CPE groups (mean 80 ml/day in CB and mean 8 ml/day in CPE). The length of the airway basement membrane and the area of mucus were measured with a digitizing computer. The volume ratio of mucus to airway lumen, which was defined as the volume ratio of mucus to airway lumen calculated as a cylinder by the length of basement membrane, was regarded as the mucus occupying ratio (MOR). MOR was significantly higher in CB lungs (4.1 +/- 1.0% in central airways and 19.6 +/- 3.8% in peripheral airways, mean +/- SE) than in NL (0.3 +/- 0.1% in central airways and 0.6 +/- 0.3% in peripheral airways, respectively) in both central and peripheral airways (p less than 0.05 and p less than 0.01, respectively), whereas no significant increase in MOR was found in CPE lungs, compared with NL. Furthermore, peripheral airway MOR was significantly higher than that of central airways in CB lungs (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1989

Effects of galactose depletion from oligosaccharide chains on immunological activities of human IgG.

We previously reported a decrease in the content of galactose residues in oligosaccharide chains of serum IgG from patients with rheumatoid arthritis, which was presumed to affect the 3 dimensional structure of CH2 domain. In the present study, we prepared the galactose depleted IgG (agalacto IgG) and characterized its immunological activities. Significant reduction in Clq binding and Fc receptor binding was observed in agalacto IgG. However, IgM rheumatoid factor binding and protein A binding were the same as with intact IgG. Our results implied the biological function of the carbohydrate moiety of human IgG.

Arthritis, Rheumatoid↗
PubMed1989

[A comparison of two doses of tamoxifen in patients with advanced breast cancer: 20 mg/day versus 40 mg/day].

In order to establish the optimal dose of Tamoxifen in the treatment of advanced breast cancer, a randomized trial comparing 40 mg/day to 20 mg/day was conducted. Thirty-four patients were entered in the study, and the results were as follows: 1) The response rates of 40 mg/day and 20 mg/day were 35.3% and 23.5%, respectively, without any significant difference between them. 2) The response rate in relation to metastatic sites were also similar at the two dose levels. 3) There was no significant difference in the median duration of response, either. 4) Among nine patients, one PR and three NC case were observed with subsequent increase of the dosage to 40 mg/day after 20 mg/day. The conclusion from this study was that 20 mg/day of Tamoxifen was suitable as an initial dosage for the treatment of advanced breast cancer. But, in certain cases who failed to respond, a dose-escalation to 40 mg/day appeared to be effective.

Adult↗
PubMed1989

[Amelioration of cisplatin-induced vomiting and anorexia by methylprednisolone].

Amelioration of cisplatin (CDDP)-induced vomiting and anorexia by methylprednisolone (MP) was studied using conscious dogs. The incidence of vomiting was 88.9% and the mean number of emetic episodes was 8.22 +/- 1.25/dog during 5 hours after i.v. administration of 1.5 mg/kg CDDP in 9 dogs. In control dogs, food intake on the day after administration of CDDP was markedly reduced to 60 +/- 22.4 g/day from 461 +/- 23 g. Continuous high-dose infusion of MP (10 mg/kg, 10 min before the start of CDDP infusion and 50 mg/kg/h for 5 h) markedly reduced the incidence (33%) and mean number of vomiting episodes (2.00 +/- 1.51/dog) and also mitigated the reduction of food intake (350 +/- 30.6 g/day). However, continuous low-dose infusion of MP (5 mg/kg, 10 min before CDDP infusion and 16.6 mg/kg/h for 5 h) showed a little effect on CDDP-induced vomiting. Plasma MP levels after the high-dose and the low-dose regimens were 6.20 +/- 0.628 micrograms/ml and 4.66 +/- 1.72 micrograms/ml, respectively, 30 min after CDDP infusion. In both cases, MP levels gradually increased and reached to those more than twice 5 hours after CDDP infusion. Bolus administrations of MP (30 mg/kg, each time) 2 hr and 30 min before CDDP infusion also significantly reduced the mean number of emetic episodes (3.22 +/- 1.33/dog) and mitigated the reduction of food intake (325 +/- 37.3 g/day). No significant changes in catecholamines, prostaglandins, vasopressin, plasma renin activity, Na+, K+, Mg++ and osmolality in peripheral blood were noted after administration of CDDP and/or MP. The results suggest that administration of MP was effective against CDDP-induced vomiting and anorexia in dogs.

Animals↗
PubMed1988

K channels of human alveolar macrophages.

The activation of macrophages has been reported to be associated with Ca-activated K permeability change. In order to study this permeability change in human alveolar macrophages, we examined alveolar macrophages electrophysiologically at a single channel level. We observed two types of Ca-activated K channel currents having conductances of 218 +/- 2 and 32 +/- 0.6 picosiemens in symmetrical 154 mmol/L KCl solutions. The characteristics, such as voltage dependency and Ca sensitivity, as well as channel conductance, were different between these two types of channel currents. Quinine (a blocker of Ca-activated K conductance), 0.5 mmol/L, reduced these channel currents by 45 +/- 8% and 31 +/- 8%. Quinine, 0.5 mmol/L, also inhibited chemiluminescence and leukotriene B4 release by 82 +/- 6 to 88 +/- 3% and 88 +/- 2%, respectively. These results suggest the presence of two types of Ca-activated K channels, which may be related to the release of inflammatory mediators from human alveolar macrophages.

Calcium↗
PubMed1988

Effects of qing-fei-tang (seihai-to) and baicalein, its main component flavonoid, on lucigenin-dependent chemiluminescence and leukotriene B4 synthesis of human alveolar macrophages.

A traditional Chinese remedy, Qing-Fei-Tang (Seihai-to, T90), has been used for treatment of chronic respiratory diseases with long-lasting cough and sputum, e.g. chronic bronchitis. We examined the effect of T90 and its main component flavonoid, baicalein, on the lucigenin-dependent chemiluminescence (CL) and leukotriene B4 (LTB4) synthesis of human alveolar macrophages (AM). AM were obtained by bronchoalveolar lavage from patients with various respiratory diseases, including sarcoidosis, idiopathic pulmonary fibrosis, bronchial asthma, chronic bronchitis and lung cancer. CL were observed by stimulating 1 x 10(5) AM with phorbol myristate acetate in the presence of lucigenin. LTB4 were generated by incubating 1 x 10(6)/ml AM with Ca ionophore A23187 for 30 min and determined by reverse phase high performance liquid chromatography and radioimmunoassay. T90 (0.2-2.0 mg/ml) and baicalein (0.1-100 microM) inhibited both CL and LTB4 production of AM in a dose-dependent fashion. These inhibitory effects were not due to cytotoxic effects of the procedure because neither 2 mg/ml T90 nor 100 M baicalein affected the viability of AM nor lactate dehydrogenase release from AM. These results suggest that T90 exerts its effect on inflammatory lung diseases through the anti-inflammatory action, i.e. inhibiting the oxidative and arachidonate metabolism of local inflammatory lung cells.

Acridines↗
PubMed1988

Bronchoalveolar lavage during inhalation provocation test in a case of farmer's lung disease.

Bronchoalveolar lavage (BAL) was performed in order to reveal inflammatory immune processes during inhalation provocation test in a patient with farmer's lung disease. Three hours after inhalation challenge the patient showed dyspnea and an increase in body temperature to 38.9 degrees C, restrictive and obstructive impairment, and a decrease in peripheral lymphocytes from, 2.8 x 10(3)/mm3 to 1.8 x 10(3)/mm3, although peripheral granulocytes increased from 4.4 x 10(3)/mm3 to 10.3 x 10(3)/mm. BAL fluid at that time showed increases in lymphocytes, granulocytes and macrophage, as well as proteins and complements, compared with that before the inhalation test. These findings indicate that with inhalation challenge in a patient with farmer's lung disease, inflammation increases vascular permeability while protein loss is followed by an increase in lymphocytes, granulocytes and macrophage; the lymphocytes migrate to the lung from peripheral blood.

Aged↗
PubMed1987

Bronchodilating effect of intravenous magnesium sulfate in bronchial asthma.

The bronchodilating effect of magnesium sulfate (MgSO4) was studied in ten asthmatic patients with mild attacks. In five patients, 0.5 mmol/min of MgSO4 was administered intravenously for 20 minutes, and the time courses of respiratory resistance, forced vital capacity, and forced expiratory volume at 1 s were studied. In another five patients, MgSO4 dose-response curves were obtained. Soon after administration began, MgSO4 relieved bronchoconstriction in a dose-dependent manner. Maximum responses (mean +/- SE) of respiratory resistance, forced vital capacity, and forced expiratory volume were 71% +/- 3%, 117% +/- 5%, and 118% +/- 1% of initial values, respectively, and were similar to the effects of additional albuterol inhalation. The infusion of MgSO4 also improved dyspnea and piping rales in three other asthmatic patients with a severe attack. We conclude that intravenous infusion of MgSO4 produces a rapid and marked bronchodilation in both mild and severe asthma and may be a unique bronchodilating agent.

Adult↗
PubMed1987

On the pathogenesis of chronic alcoholic pancreatitis from the viewpoint of experimental results in rats.

To elucidate the pathogenesis of chronic alcoholic pancreatitis, light-microscopic and electron microscopic observations of pancreases from Wistar strain rats given 20% ethanol ad lib, instead of water, were performed. Results were as follows: (1) In 3 (11%) rats, focal lobular unit acinar cell damage was observed under light-microscopy. In these cases, the intercalated ducts and centroacinar cells showed proliferation independently of protein plugs in ducts. (2) After ethanol intake, several degenerative changes in the acinar cells and ductular cells were observed under electron microscopy. The earliest and most consistent change was the irregular formation of microvilli and interdigitation between the parenchymal cells, accompanied by widening of the intercellular space, especially between the acinar and centroacinar cells. After three months of ethanol intake, an increase in the lysosomes and mitochondrial alteration occurred in acinar cells, and after six months of ethanol ingestion, there was tortuous ductular proliferation accompanied by the degeneration of the ductular cells. In addition to these parenchymal changes, the capillary endothelium and nervous tissue of the pancreas showed occasional degenerative changes after three to six months of ethanol intake. These results suggest that repeated degeneration and regeneration of the ductular cells results in deformation of ductular structures, with subsequent stenosis, and represents the primary event in the development of chronic alcoholic pancreatitis in rats.

Alcoholism↗
PubMed1987

Kinetic characteristics and binding process of substrate analogs to the adenosine deaminase in the marine mussel, Mytilus edulis.

1. The purified mussel enzyme deaminated several adenosine analogs with different Km and relative Vmax values. Affinity for adenine was similar to that for adenosine but the deamination rate was extremely slow. 2. Purine riboside was competitive, coformycin was a tight, slow binding inhibitor, and inhibition by both these compounds was pH-dependent. 3. Inosine, hypoxanthine, guanosine and 6-mercapto-purine riboside were slightly inhibitory. 4. The results suggested that initial binding of the substrate was guided by the adenine moiety followed by a stereospecific steering due to a ribose-dependent distortion in the complex to facilitate nucleophilic attack at C-6.

Adenosine↗
PubMed1987

Affinity difference of adenosine deaminases for the purine riboside-epoxyactivated Sepharose 6B column.

The small-size adenosine deaminase (Mr = 35,000 and 43,000) in calf intestinal mucosa, frog liver and scallop adductor muscle and the large-size deaminase (Mr = 100,000) in frog liver probably formed by adding a conversion protein to the small enzyme, were tightly bound to the purine riboside affinity column. Binding of the other large-size enzymes (Mr = 140,000) in the midgut gland of scallop and mussel to the column was not successful. It seems that the binding difference does not depend on a change in affinity between active site and ligand but rather on the stereospecific positioning of active site in the enzyme molecules.

Adenosine Deaminase↗