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Biomedical subjects

M Akagi

Publications and source records attributed to M Akagi.

At least 73 records · Page 4Linked to original sources
PubMed1995

Inhibitory effect of epinastine on superoxide generation by rat neutrophils.

We studied the effects of antiallergic drugs, epinastine, ketotifen, oxatomide, mequitazine and cromolyn sodium on superoxide anion (O2-) generation from rat neutrophils. Epinastine, ketotifen, oxatomide and mequitazine dose-dependently prevented the N-formyl-Met-Leu-Phe- and phorbol 12-myristate 13-acetate-induced O2- generation, but cromolyn sodium did not prevent it. When membrane and cytosol fractions were incubated with each drug, epinastine, ketotifen and mequitazine prevented O2- generation. On the other hand, when only the membrane fraction was incubated with each drug, ketotifen and mequitazine prevented O2- generation, but epinastine did not. Epinastine may inhibit the NADPH oxidase system through the obstruction of NADPH oxidase-associated cytosol components.

Animals↗
PubMed1995

New criteria for the radical repair of congenital heart disease with pulmonary hypertension. In order to avoid postoperative residual pulmonary hypertension.

In congenital heart disease (CHD) with pulmonary hypertension (PH) resulting from high pulmonary flow, we sometimes experience patients whose PH continues even after the normalization of flow following surgery. Preoperative identification of these patients is difficult even using direct hemodynamic measurements at cardiac catheterization. The purpose of this study is to interpret the state of the pulmonary vascular bed more precisely using a new theoretical approach and to present the criteria available for avoiding residual PH. During preoperative routine catheter examination in CHD patients with PH we applied the Windkessel model to the pulmonary circulation and calculated the diastolic time constant (Td) of the pulmonary circulation. Td of Group 1 (0.50 +/- 0.03 sec), 6 patients who manifested residual PH after surgery, was higher than that of group 2 (0.23 +/- 0.14 sec), 42 patients with normalized pulmonary artery pressure after surgery. Furthermore, the relationships between Td and pulmonary blood flow (Qp) or pulmonary to systemic flow ratio (Qp/Qs) were very sensitive for distinguishing between these two groups. Group 1 was located in the left-upper quadrant of the graph of Td vs Qp or Td vs Qp/Qs relationships, whereas group 2 was located in the right-lower quadrant. The relationships between Td and Qp or Qp/Qs were considered to reflect the pathological change in the pulmonary vasculature more precisely. As a consequence, they would be very useful in understanding the state of the pulmonary vascular bed and avoiding residual PH.

Blood Pressure↗
PubMed1995

Contribution of platelet activating factor (PAF) in histamine-induced model of nasal allergy in rats.

Histamine-induced nasal hyperpermeability was measured in rats. Perfusion of histamine elicited a biphasic increase of nasal vascular permeability, and an increase of concentration of platelet-activating factor (PAF) in the perfusate. Both phases were prevented by pretreatment with diphenhydramine (1 mg/kg, p.o.), a histamine H1-receptor antagonist, and the second increase of vascular permeability was prevented by pretreatment with 3-[4-(2-chlorophenyl)-9-methyl-6H-thieno [3,2-f] [1,2,4]-triazolo [4,3-alpha] [1,4] diazepin-2-yl]-1-(4-morpholinyl)-1-propane (WEB 2086) (10 mg/kg, p.o.), an anti PAF agent. The time-course of PAF-induced nasal hyperpermeability was similar to that of the second increase induced by histamine. These findings suggest that PAF released by histamine from nasal mucosa plays an important role in nasal allergy, especially in the late phase.

Animals↗
PubMed1995

Effect of loratadine on immediate and delayed type hypersensitivity reactions.

Loratadine (CAS 79794-75-5) was effective in inhibiting the contractions of the ileum induced by histamine in guinea pigs. The drug also caused an anti-acetylcholine, anti-serotonin and anti-leukotriene D4 (LTD4) effect. In addition, loratadine inhibited the synthesis of leukotrienes more potently than ketotifen. On the other hand, in in vitro studies of histamine release from rat peritoneal mast cells induced by compound 48/80 or lung fragments in actively sensitized guinea, pigs, loratadine elicited a significant inhibition at a concentration of 5 mumol/l. In ex vivo studies, the drug inhibited histamine release from lung fragments induced by concanavalin A, and significant effect lasted for 24 h when the drug was administered at a dose of 20 mg/kg. The drug inhibited LTD4 release as well as histamine from lung fragments in actively sensitized guinea pigs. Loratadine inhibited not only 45Ca uptake into the rat peritoneal mast cells but also Ca2+ release from the intracellular Ca store induced by compound 48/80 or A23187. Loratadine increased cAMP content in rat lung preparation while decreasing cGMP content. Loratadine caused no significant change in order parameter and phospholipase A2 activity. The drug was more potent than ketotifen and terfenadine in inhibiting antigen-induced increase in airway resistance in guinea pigs. In addition, the effect of loratadine on airway resistance was sustained for 12 h. Loratadine inhibited an increase in dye leakage into the nasal cavity in rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1995

A comparative study of myocardial troponin T levels in patients undergoing hemodialysis.

This study included 25 patients receiving hemodialysis (HD) but in whom diabetes mellitus was not the primary disease (HD-non DM group), 25 patients receiving hemodialysis with diabetes mellitus as the primary disease (HD-DM group), and 50 patients with diabetes mellitus who had not yet been treated with hemodialysis (DM group). The following markers of myocardial injury were measured in these patients: troponin T (TnT), creatine kinase (CK), myoglobin (Mb), and myosin light chain-1 (MLC-1). No significant correlation was found between myocardial TnT and Cr in any study group. The Mb and MLC-1 values in patients receiving HD were markedly higher than normal regardless of the primary disease involvement, while myocardial TnT was found to be only slightly abnormal. These results suggest that myocardial TnT may be a more useful marker of myocardial injury in HD patients than the markers in current use. In the present investigation, myocardial TnT was the only marker that was higher in the HD-DM group than in the HD-non DM group. This suggests the possibility that the HD-DM group included more patients with arteriosclerotic lesions, such as myocardial injury.

Aged↗
PubMed1995

Role of histamine H3 receptor on hypoxia-reoxygenation-induced cardiac dysfunction in guinea pigs.

Hypoxia elicited a remarkable decrease in contractility and heart rate in isolated right atria from guinea pigs, a decrease which recovered partially during reoxygenation. Histamine content increased during hypoxia and decreased during reoxygenation. However, hypoxia induced a marked degranulation of mast cells. Pretreatment with alpha-methylhistamine (100-300 nM) recuperated control level contractility and heart rate, and prevented the hypoxia-reoxygenation-induced leakage of creatine phosphokinase (CPK). On the other hand, pretreatment with thioperamide (100-300 nM) decreased contractility and heart rate dose-dependently, and prevented recovery during reoxygenation. These data shows that cardiac histamine may play an important role in the protection against hypoxia-reoxygenation injury through the H3 receptor.

Adenosine Triphosphate↗
PubMed1994

Frequent loss of heterozygosity of the long arm of chromosome 7 is closely associated with progression of human gastric carcinomas.

Loss of heterozygosity (LOH) on the long arm of chromosome 7 was examined using 5 polymorphic marker probes on 98 gastric carcinomas to elucidate a novel locus for development and progression of the tumors. Twenty-six (32%) of 82 informative cases showed LOH on 7q on at least one locus of 5 loci. Among 5 loci, LOH at D7S95 locus was most frequent, the incidence being 53% in well-differentiated gastric carcinomas and 33% in poorly differentiated and scirrhous gastric carcinomas respectively. At 3 loci, c-met, D7S63 and D7S22, the incidence of LOH was about 30% and 10% in well-differentiated and poorly differentiated gastric carcinoma cases respectively. In contrast, LOH at D7S64 was not detected in any gastric-carcinoma cases. Deletion mapping of 7q revealed that D7S95 locus was the essential region of LOH. Eight (62%) of 13 cases with LOH at D7S95 locus belonged to the most advanced stage grouping. Furthermore, 6 (75%) of 8 cases with abdominal dissemination showed LOH at D7S95. Therefore, cases with LOH at D7S95 showed significantly worse prognosis than the cases without the LOH in the stage-III and stage-IV groups. These findings overall suggest that D7S95 locus on 7q may contain a candidate suppressor gene for the progression of gastric carcinoma.

Adenocarcinoma↗
PubMed1994

Superoxide anion-induced histamine release from rat peritoneal mast cells.

We investigated the properties of superoxide anion (O2-)-induced histamine release from rat peritoneal mast cells using superoxide anion radicals obtained from potassium superoxide (KO2). KO2 elicited a rapid histamine release in a dose-dependent fashion, without lactate dehydrogenase (LDH) release. The KO2-induced release was temperature- and energy-dependent. KO2 rapidly increased the intracellular free Ca2+ concentration, accompanied by a marked increase of Ca(2+)-uptake. These findings indicate that the increase in intracellular Ca2+ concentration is involved in the initiation of KO2-induced histamine release, and KO2 could be used as an agent of O2(-)-induced biological reactions.

Animals↗
PubMed1994

[Assessment for development of superficial colorectal neoplasm--endoscopic and clinicopathologic analysis of 149 submucosal invasive carcinomas].

We performed the endoscopic and clinicopathologic analysis for the development of superficial colorectal carcinoma, using 149 submucosal (sm) invasive colorectal carcinomas. It was observed that superficial colorectal carcinomas had a tendency to rise by their sm massive invasion. In this study, we judged that the sm colorectal carcinomas originated from superficial colorectal carcinoma were 37 (25%) of 149 lesions, and their distribution in the colon and rectum was similar to that of advanced colorectal carcinomas, although the lesions originated from non-superficial (polypoid) colorectal carcinoma did not show so tendency. On the other hand, sm colorectal carcinomas originated from superficial colorectal carcinoma contained the evident adenomatous components in 7 (19%) of 37 lesions and had significantly higher incidence of lymph node metastasis than those originated from non-superficial (polypoid) carcinoma. These results suspected the facts as follows; 1) Superficial early colorectal carcinoma may be compatible as the origin to advanced colorectal carcinoma and has higher malignant potential than non-superficial early carcinoma. 2) Superficial colorectal carcinoma might also have the route of the development of "adenoma-carcinoma sequence", as well as "de novo" histogenesis.

Adenoma↗
PubMed1993

Antiallergic profile of the novel H1-antihistaminic compound levocabastine.

Levocabastine hydrochloride (R50 547, CAS79516-68-0) caused no inhibitory effect on the histamine release from rat peritoneal mast cells induced by compound 48/80, A23187 and concanavalin A. However, the drug inhibited histamine release from passively sensitized mast cells and passive peritoneal anaphylaxis in rats, though higher concentrations or doses were required. Moreover, levocabastine provided a relatively potent inhibitory effect on histamine release from lung pieces of actively sensitized guinea pigs exposed to antigen, and simultaneously the drug prevented a decrease in the cyclic AMP (cAMP) content. Levocabastine potently inhibited histamine-induced cutaneous reactions in rats and the drug also prevented histamine-induced contraction of isolated guinea pig ileum. Levocabastine did not induce any significant changes in platelet aggregation or in the contraction of guinea pig ileum induced by platelet activating factor (PAF). However, the drug inhibited eosinophil migration induced by PAF. The chemotaxis of neutrophils induced by N-formyl-methionyl-leucylphenylalanine (fMLP) was also inhibited by levocabastine in a dose-dependent fashion. Levocabastine has no influence on the order parameter tested with liposomes, suggesting that the drug provides no significant effect on the membrane fluidity of lipid bilayer. These results seem to indicate that the antiallergic effect of levocabastine is mainly dependent on its potent antihistaminic activity.

Anaphylaxis↗
PubMed1993

Spectroscopic characterization of heterochiral DNAs.

We have synthesized heterochiral dodecadeoxynucleotides having an unnatural L-nucleotide residue, and have investigated their structures by ultraviolet (UV) absorption, circular dichroism (CD) measurements and nuclear magnetic resonance (NMR) spectroscopy. It was clearly shown that the overall structures of the heterochiral 12-mers are a right-handed B-conformation and the unnatural L-nucleotide residue in the heterochiral 12-mer (L-4) forms stable Watson-Crick type base-pairing with the natural complementary residue. In this double helix (L-4), the unnatural G4 residue has an S-type sugar conformer and a low-anti glycosidic torsion angle. From the properties of an enantiomer, natural nucleotides may possibly form a low-anti left-handed B-form duplex with the aid of certain factors.

Base Sequence↗
PubMed1992

Randomized adjuvant trial to evaluate the addition of tamoxifen and PSK to chemotherapy in patients with primary breast cancer. 5-Year results from the Nishi-Nippon Group of the Adjuvant Chemoendocrine Therapy for Breast Cancer Organization.

BACKGROUND: A randomized adjuvant trial was conducted from October 1982 to January 1985 to evaluate the addition of tamoxifen (TAM) to combination chemotherapy with perioperative mitomycin C (MMC) and ftorafur (FT) for patients with estrogen receptor (ER)-positive tumors and the addition of PSK, a biologic response modifier, to MMC+FT chemotherapy for patients with ER-negative tumors in operable Stage IIA, IIB, and IIIA cancer. The doses used were 20 mg of oral TAM daily, 600 mg of oral FT daily, and 3 g of oral PSK daily for 2 years. Intravenous MMC (13 mg/m2) was given on the day of operation. METHODS: A total of 967 patients were entered and randomized by stratification based on ER status and staging (1978 International Union Against Cancer [UICC] criteria at the time of trial execution). Of 967 patients, 914 (94.5%) were evaluable. At 5-year follow-up, significant prolonged overall survival (OS) and relapse-free survival (RFS) times were seen with the addition of TAM in patients with ER-positive and Stage IIIA T3N0 cancer (1987 UICC-American Joint Committee on Cancer [AJCC] criteria); however, no significant survival benefit from TAM was seen in patients with ER-positive and Stage IIA T2N1 cancer. There was no significant difference between regimens, with or without PSK, in patients with ER-negative disease. RESULTS: Results of subset analyses suggested a benefit from TAM in postmenopausal patients with ER-positive and Stage IIA T2N1 cancer and a benefit from PSK in patients with node-negative, ER-negative, and Stage IIA T2N1 cancer. CONCLUSIONS: The 5-year results of the current trial showed a survival advantage by the addition of TAM to chemotherapy in patients with ER-positive and Stage IIIA T3N0 cancer.

Adjuvants, Immunologic↗
PubMed1992

Effects of 1,3-chelation induced by cis-diamminedichloroplatinum(II) on the stability of DNA duplexes.

Several 1,3-intra-strand cross-linked decadeoxynucleotide duplexes, modified with cis-diamminedichloroplatinum(II) (cis-DDP), and their base substitution analogues at the complementary site to the intervening base of the coordination sites, were synthesized and measured for UV-melting profiles to determine melting temperature (Tm) values. The results indicated the thermal stability of the oligonucleotide duplexes containing Pt-induced 1,3-intra-strand cross-linking did not depend on the kind of intervening base of the coordination site but rather on its complementary base. These results may explain the mutagenicity of cis-DDP from a chemical aspect.

Base Sequence↗
PubMed1992

Synthesis and properties of mirror-image DNA.

We have investigated the conformations of the hexadeoxyribonucleotide, L-d(CGCGCG) composed of L-deoxyribose, the mirror image molecule of natural D-deoxyribose. In this paper, we report the synthesis of four L-deoxynucleosides and the L-oligonucleotide-ethidium bromide interactions. The L-deoxyribose synthon 9 was synthesized from L-arabinose with an over all yield of 28.5% via the Barton-McCombie reaction. The L-deoxynucleosides were obtained by a glycosylation of appropriate nucleobase derivatives with the 1-chloro sugar 9. After derivatization to nucleoside phosphoramidites, L-deoxycytidine and L-deoxyguanosine were incorporated into a hexadeoxynucleotide, L-d(CGCGCG) by a solid-phase beta-cyanoethylphosphoramidite method. This L-hexanucleotide was resistant to digestion with nuclease P1. The conformations of L-d(CGCGCG) were an exact mirror image of that of the corresponding natural one as described previously, and the conformations of the L-d(CGCGCG)-ethidium bromide complex were also the mirror images of those of the D-d(CGCGCG)-ethidium bromide complex under both low and high salt conditions. These results suggest that ethidium bromide prefers not a right-handed helical sense, but the base-base stacking geometry of the B-form rather than that of the Z-form. Thus, L-DNA would be a useful tool for studying DNA-drug interactions.

Chromatography, High Pressure Liquid↗
PubMed1992

Action of Escherichia coli heat-stable enterotoxin II on isolated sections of mouse ileum.

When Escherichia coli STII was applied to the serosa of the ileum at a concentration of 40 micrograms/ml, an acceleration of the spontaneous motility and a weak contraction were induced 2-3 min later. The induction was not affected by the addition of atropine (10(-6) M), but was abolished by the addition of papaverine (10(-4) M). When STII was applied to the mucosa, the acceleration of the spontaneous motility appeared 7-8 min later, but a contraction was not induced. These results suggest that STII acts directly on muscle cell of the ileum and enhances the spontaneous motility of the intestine.

Animals↗
PubMed1992

Early postoperative chemotherapy following noncurative resection for patients with advanced gastric cancer.

We studied the effect of early postoperative chemotherapy, including 5-fluorouracil (5-FU) for 5 days for patients with gastric cancer following noncurative resection. The study was prospectively randomised and controlled, and 162 (87.1%) of 186 were eligible candidates for statistical assessment. Patients randomised to group A received therapy that is used widely to treat patients with gastric cancer in Japan; mitomycin C (MMC), OK-432, UFT and PSK. Patients randomised to group B received the same drugs given to group A plus 5-FU bolus injections for 5 days, beginning on postoperative day 2. There were no differences in prognostic factors and doses of the drugs prescribed, except for 5-FU. There was no difference in the toxicity rate between the groups. Generalised Wilcoxon test revealed a P value of 0.169, and the 50% survival rate improved 1.4-fold in patients with gastric cancer treated with early postoperative chemotherapy of MMC, OK-432 plus 5-FU injection.

Aged↗
PubMed1992

Antiallergic effect of epinastine (WAL 801 CL) on immediate hypersensitivity reactions: (I). Elucidation of the mechanism for histamine release inhibition.

Epinastine caused an inhibition of histamine release from rat peritoneal mast cells induced by both antigen-antibody reaction and compound 48/80. Epinastine was similarly effective in inhibiting compound 48/80-induced histamine release not only from isolated rat peritoneal mast cells but also from rat mesenterial pieces. Also, histamine release from lung pieces obtained from actively sensitized guinea pigs after exposure to antigen challenge was markedly inhibited by epinastine. The drug was effective in inhibiting not only Ca2+ uptake into lung mast cells in actively sensitized guinea pigs but also Ca2+ release from the intracellular Ca store of rat peritoneal mast cells exposed to both compound 48/80 and substance P. No significant changes were observed in phosphodiesterase activity in rat peritoneal mast cells treated with epinastine, while adenylate cyclase activity was augmented by epinastine. Epinastine has no inhibitory effect on histamine release induced by Ca2+ or IP3 from permeabilized mast cells. However, the drug significantly and dose-dependently suppressed calmodulin activity suggesting that histamine release inhibition due to epinastine may be partly attributable to Ca(2+)-calmodulin dependent process(es). The drug caused no visible changes in thermodynamic behavior of lipids, either in order parameter or in differential scanning calorimetry, indicating that the drug has no influence on membrane fluidity.

Adenylyl Cyclases↗