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Biomedical subjects

M Akagi

Publications and source records attributed to M Akagi.

At least 19 recordsLinked to original sources
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↗
PubMed1992

Application of L-DNA to the study of the specific DNA recognition mechanism of bleomycin.

The hexadeoxynucleotide analog, L-d(CGCGCG) composed of L-deoxyribose was synthesized and clearly shown to have the same conformation and dynamic properties with natural D-d(CGCGCG) except for chirality with CD spectra. This unnatural hexanucleotide was not cleaved by bleomycin, an antitumor DNA cleaving drug, but was able to bind to the DNA binding domain of bleomycin to a similar extent with the natural one. These results strongly suggest the importance of the other moiety than the DNA binding domain for the specific DNA recognition of bleomycin. Thus, L-oligonucleotides are useful for the study of DNA-drug interactions.

Binding Sites↗
PubMed1991

Photo-induced formation of the 2-deoxyribonolactone-containing nucleotide for d(ApCpA); effects of neighboring bases and modification of deoxycytidine.

Previously, we reported the formation of a 2-deoxyribonolactone-containing nucleotide by UV irradiation of d(ApCpA). In this paper, we report some mechanical feature of this novel photoreaction. From the results of photolysis of d(GpCpG), this reaction is independent of neighboring bases. On photolysis of deoxycytidine at acidic pH, 2-deoxyribonolactone was produced with 74.2% isolated yield. And effects of some modifications of deoxycytidine were investigated. The results suggest that hydrates are possible intermediates for this reaction and the protonation may be essential not for deoxycytidine, but for the intermediates.

Adenine↗
PubMed1991

Interstrand cross-linking of the hexadeoxynucleotide d(TACGTA) upon reaction with trans-diamminedichloroplatinum(II).

The reaction of trans-diamminedichloroplatinum(II), an inactive isomer of cisplatin, with d(TACGTA) was performed in aqueous solution, and the interstrand cross-linked adduct was isolated on a preparative scale. This adduct was characterized by 1 M thiourea treatment, atomic absorption spectroscopy, enzymatic digestion and 1H NMR as platinum coordinated to two molecules of d(TACGTA) at the N7 atom of the guanine residue. This interstrand cross-linked adduct did not form a duplex structure in the conditions where the free hexanucleotide adopts it.

Chromatography, High Pressure Liquid↗
PubMed1991

Role of the cytoskeleton in Ca2+ release from the intracellular Ca store of rat peritoneal mast cells.

In order to study the role of the cytoskeleton in histamine release from mast cells, the effects of cytochalasin D, cholchicine and vinblastine on Ca2+ release from the intracellular Ca store induced by compound 48/80 were investigated by means of a video-intensified microscopy system. When the quin 2-loaded mast cells were stimulated by 0.35 micrograms/ml of compound 48/80, a rapid increase in intracellular Ca2+ was observed. At concentrations higher than 10(-6) M, both colchicine and vinblastine pretreatments significantly inhibited the increase in intracellular Ca2+ concentrations caused by compound 48/80, although cytochalasin D had no effect. When permeabilized mast cells were exposed to potassium-antimonate solution, microtubules became attached to the endoplasmic reticulum, where many dots of Ca-antimonate were observed; in some areas, the microtubules interconnected the endoplasmic reticulum and granules in the mast cells. From the results of the present study, it was assumed that microtubules play some important role in the processes leading to Ca2+ release from the intracellular Ca store.

Aminoquinolines↗
PubMed1991

The existence of filaments connecting the granules and the cell membrane in rat peritoneal mast cells.

SEM images of rat peritoneal mast cells showed that microtubule-like filaments seemed to penetrate the granules and project several branches just beneath the granular surface. Each granule appeared to be a cluster of microgranules. TEM observations frequently revealed microtubules connecting the granule surface to the subplasmalemmal network or to the adjacent granule surface and on some occasions, microtubules also appeared to penetrate the granule membranes. Moreover, TEM revealed that individual granules seemed to consist of a mass of microgranules, each 10-15 nm in diameter; freeze-fracture images showed similar configurations. These findings suggest that the microtubule-like filamentous structures in mast cells play a role corresponding to that of the open canalicular system in platelets.

Animals↗
PubMed1991

Comparative study of the adverse effects of various radiographic contrast media, including ioversol, a new low-osmolarity medium. II. The complement system and endothelial cells.

The effects of ioversol, iohexol, iopamidol and meglumine sodium amidotrizoate (MSA) on the complement system and endothelial cells were investigated. The protein bindings of the radiographic contrast media (RCM), each tested with guinea pig plasma, were less than 1%. When guinea pig serum was incubated with any of the RCM, activation of the complement system, which leads to hemolysis, was not influenced by the nonionic agents, ioversol, iohexol or iopamidol. However, MSA, an ionic agent, significantly reduced hemolytic activity at 370 mgI/ml. Perfusion of the abdominal aorta with nonionic agents did not elicit significant endothelial damage; ioversol induced the least damage among the nonionic RCM, while MSA caused remarkable endothelial damage. Although MSA caused a marked release of endothelin-1 from cultured endothelial cells obtained from porcine aorta, nonionic RCM did not induce significant endothelin-1 release; no influence was elicited by ioversol and iohexol caused a weak suppression, while iopamidol had the opposite effect. These results indicate that ioversol could be used as a safe contrast medium in intravascular administration.

Animals↗
PubMed1991

Dislocation of the peroneal tendons in neonates and infants.

Twenty-three cases of dislocation of the peroneal tendons were found during routine orthopedic examinations of neonates and infants. All but one case was without foot deformity. One case was treated with a cast, and the others received no treatment. Follow-up observations revealed that the dislocations resolved spontaneously in almost all cases. This condition seems to be not as rare as had been previously considered. Dislocations of the peroneal tendons in neonates and infants without foot deformity should be untreated and allowed to resolve spontaneously.

Ankle Joint↗
PubMed1991

[A successful surgical treatment of cor triatriatum with VSD, PDA and CoA].

A successful repair of cor triatriatum with VSD, PDA and CoA is reported. A two-month-old boy was admitted for evaluation of growth failure and cyanosis. Physical examination on admission revealed systolic murmurs at left sternal border. Chest X-ray showed increased pulmonary vascularities without cardiomegaly. Echocardiography showed abnormal wall in left atrium with VSD, PDA and CoA. An emergency operation consisting of patch closure of VSD, ligation of PDA and resection of the anomalous left atrial membrane were performed. At postoperative course, an episode of pulmonary hypertension crisis happened. But the patient tolerated this episode and survived.

Aortic Coarctation↗
PubMed1991

[Successful surgical treatment of total anomalous pulmonary venous connection (supracardiac Ib type) showing an unusual shape of the pulmonary veins in an infant].

An experience of a 9-month-old infant with Darling's type Ib of total anomalous pulmonary venous connection is presented. In this case, the left pulmonary vein traveled horizontally behind the atrium, entered the right thoracic cavity and drained into the SVC together with the right lower, middle and upper pulmonary veins. The patient was treated with repair using Gersony-Malm's method and plasty of SVC because of the stenosis of the common pulmonary vein's entrance to the SVC. Her postoperative course was uneventful, and the result was satisfactory. To our knowledge, our case is the first successful correction not associated with other complex cardiac anomalies in the world.

Female↗
PubMed1990

Serum carcinoembryonic antigen level increases correlate with tumor progression in patients with differentiated gastric carcinoma following noncurative resection.

Serum carcinoembryonic antigen (CEA) levels were determined serially in 30 preoperative and postoperative patients with differentiated and 47 with undifferentiated gastric cancers. Macroscopic noncurative resection of the stomach was done for those patients. There was no difference between survival curves in the differentiated and undifferentiated cases, and the 50% survival was 13.1 months for the differentiated group and 12.5 months for the undifferentiated group. Preoperative serum CEA levels were 10.4 +/- 5.2 ng/ml for the differentiated and 4.0 +/- 1.6 ng/ml for the undifferentiated cases, and CEA-positive rates were 20.0% for the differentiated and 14.9% for the undifferentiated cases. There was no difference in preoperative CEA values with regard to tissue types. In the course of tumor progression, CEA levels increased during the first postoperative year in the differentiated cases and related reciprocally to decreases in survival rates. Little change was noted in the undifferentiated cases. Therefore, the serial postoperative assay of serum CEA levels has predictability with regard to tumor progression in patients with a differentiated gastric cancer.

Adult↗
PubMed1990

Histamine release induced by histone and related morphological changes in mast cells.

When isolated rat peritoneal mast cells were exposed to histone mixture, both histamine release and degranulation were evoked rapidly and dose-dependently at concentrations higher than 1 microgram/ml in a Ca-free medium. All of the histone subfractions (H1, H2A, H2B, H3 and H4) induced histamine release from mast cells in a Ca-free medium and, as in the case of histone mixture, the amount of histamine release was reduced by addition of Ca2+. By means of high-voltage electron microscopy, at least three types of degranulation were observed in mast cells exposed to histone mixture: (1) microfilament-associated degranulation, (2) extrusion of granules with the surrounding membrane, and (3) mass degranulation.

Animals↗