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Biomedical subjects

M Kodama

Publications and source records attributed to M Kodama.

At least 541 records · Page 30Linked to original sources
PubMed1982

A correlation of the rate of N-hydroxylation of aminoazo dyes with their carcinogenic activity in the rat.

The rate of formation of N-hydroxy-N-methyl-4-aminoazobenzene (N-OH-MAB) derivatives from N,N-dimethyl-4-aminoazobenzene (DAB) derivatives and from N-methyl-4-aminoazobenzene (MAB) derivatives was measured by the e.s.r. spectroscopy, and the rate of N-demethylation of DAB derivatives was measured by h.p.l.c. The rate of formation of N-OH-MAB derivatives from DAB derivatives showed a strong correlation with their carcinogenic activity. This reaction occurs in two-steps, i.e. N-demethylation followed by N-hydroxylation. The rate of N-demethylation of DAB derivatives was not correlated with their carcinogenic activity. On the other hand, the rate of N-hydroxylation of MAB derivatives was well correlated with the carcinogenic activity of corresponding DAB derivatives. These results suggest that the carcinogenic activity of DAB derivatives in the rat was dependent upon the enzyme concerned with N-hydroxylation. The positive carcinogenicity is limited to those derivatives with a rate of N-hydroxylation above the threshold value.

Animals↗
PubMed1982

Gonyautoxin associated with RNA-containing fraction in the toxic scallop digestive gland.

A nontoxic high molecular substance associated with some paralytic shellfish poisons was separated by Sephadex G-50 gel filtration from the toxic digestive glands of the scallop Patinopecten yessoensis fed the causative plankton Protogonyaulax tamarensis. Unlike the corresponding fraction from the nontoxic digestive glands, the substance released gonyautoxins II and III on digestion with RNase T2, suggesting that it is associated with an RNA of P. tamarensis. It is possible that the toxification of scallop is partly due to the toxins already accumulated in Protogonyaulax cells, and partly due to incorporation of this precursor, which releases the toxins as a result of enzymic processes in the shellfish.

Animals↗
PubMed1982

A 13C nuclear magnetic resonance study of histone H1 in 2-chloroethanol and aqueous solutions. Identification of peaks characteristic of secondary folding.

A 13C NMR study of calf thymus histone H1 in both aqueous solution and 2-chloroethanol solution was performed to clarify the folding behavior in these systems. To ascertain the general trend of displacements of 13C shifts upon folding in an enhanced manner, the latter solvent was employed since it is known to increase the amount of alpha-helix content in histone to about 50%. Generally, upfield displacements of C beta signals (up to 1.4 ppm) were clearly identified as helix-induced peaks, although displacements of C alpha signals, which might be much larger, were not easily distinguished because of overlap of several broadened signals with reduced peak intensities. In particular, we found that the upfield displacement of Ala C beta, by 1.1 ppm, is an excellent probe to monitor the presence of alpha-helix conformation in both 2-chloroethanol and aqueous solutions. This upfield displacement of the C beta signal in alpha-helix segment is consistent with our previous findings for a number of model polypeptides by ordinary and solid-state high resolution 13C NMR spectroscopy. Further, we observed that 13C peaks of several residues (Tyr, Ser, Leu, Ile, and Val) were suppressed as a result of specific folding of H1 in the presence of NaCl in aqueous solution. Thus, it appears that several tightly-folded segments whose 13C signals were considerably broadened are located in the central core portion.

Amino Acids↗
PubMed1982

Electron spin resonance study on the metabolism of 2-naphthylamine and 1-naphthylamine in rat liver microsomes.

Incubation of 2-naphthylamine (2-NA) with rat liver microsomes fortified with NADPH resulted in the formation of two types of free radicals which were identified as being due to N-hydroxy-2-naphthylamine and 2-amino-1-naphthol. The former radical was shown to be oxidized further to 2-nitrosonaphthalene radical. Compared with the case of the constitutive microsomes, the amount of the free radicals increased progressively on using the microsomes from methylcholanthrene (MC)-induced or phenobarbital (PB)-induced rats. On the other hand, the amount of the free radical formed from 1-naphthylamine (1-NA) was much less than that from 2-NA, so that the radical structure was not identified unambiguously. The enzymes involved in this case were not induced by either MC or PB. Thus, from the viewpoint of free radical formation, the metabolic patterns of 2-NA and 1-NA are quite different and such different behavior might be correlated with the distinct difference in their carcinogenicities. From the inhibitory effects of carbon monoxide, SKF-525A, alpha-naphthoflavone and 1-(1-naphthyl)-2-thiourea on the free radical formation, it was concluded that both mixed function oxidases (cytochrome P-450s) and mixed function amine oxidase (dimethylaniline monooxygenase) are involved in the metabolism of 2-NA.

1-Naphthylamine↗
PubMed1982

[Experimental and clinical studies of cefmenoxime in the field of obstetrics and gynecology].

The study group was organized to evaluate the usefulness of cefmenoxime (CMX) injection, a new synthetic cephalosporin, for the treatment of infections in the field of obstetrics and gynecology. Fundamental and clinical studies were made by the society and the following results were obtained. 1. The peak distribution of CMX's MIC for E. coli, Klebsiella sp., Enterobacter sp., Bacteroides sp. and Peptococcus sp. isolated from obstetrical and gynecological infections with relatively high frequencies area 0.1, less than or equal to 0.05, 0.2, 3.13, 1.56 micrograms/ml, respectively, with an inoculation of 10(6) cells/ml. 2. When 1 g of CMX is administered by intravenous drip infusion for 1 hour, the maximum concentrations in various tissues of female genital organs were as follows: 14.2 and 13.2 micrograms/g in ovary and oviduct, respectively, at 1.20 hours after the start of administration, and 16.9 and 26.3 micrograms/g in corpus uteri and cervix uteri, respectively, after 1 hour. As for the transfer to the exudate in the pelvic dead cavity, the peak concentration was 15.6 micrograms/ml after 2.13 hours. 3. In the clinical studies, CMX was given to 258 cases with female genital organ infections and others. As for the clinical effects, with exclusion of 3 cases in which other antibiotics are concomitantly used, responses were excellent in 76 cases, good in 162 cases and poor in 17 cases, among 255 cases in total. The efficacy rate was 93.3%. The efficacy rates by diseases were 97.1% (68/70) for intrauterine infections, 88.8% (79/89) for intrapelvic infections, 98.4% (62/63) for adnexitis, and 100% (23/23) for infections of external genital organs. As for the clinical effects on causative bacteria, the efficacy rates were 100% (19/19) for single infections due to Gram-positive bacteria, 94.8% (55/58) for single infections due to Gram-negative bacteria, and 88.2% (15/17) for single infections due to anaerobic bacteria. And its efficacy rates were 89.6% (69/77) for mixed infection cases. Side effects were observed in 2 cases (0.8%); 1 case with eruption, and 1 case with diarrhea and vomiting. As for abnormal laboratory findings, lower white blood cell count was observed in 2 cases and elevation of the values regarding hepatic functions in 9 cases. All cases were returned to the normal after the completion of the administration. Cefmenoxime showed a satisfactory clinical efficacy and a potent bacteriological effect in treatment of the infections in the field of obstetrics and gynecology, and it has been concluded that cefmenoxime will be useful addition to the antibiotics for the therapy of these infections.

Adolescent↗
PubMed1982

N-Hydroxylation enzymes of carcinogenic aminoazo dyes: possible involvement of cytochrome P-448.

N-Hydroxylation reactions of 3'-methyl-N,N-dimethyl-4-aminoazobenzene (3'-Me-DAB) and 3'-methyl-N-methyl-4-aminoazobenzene (3'-Me-MAB) were studied by measuring the nitroxide radical generated from N-hydroxylated products of these aminoazo compounds. N-Hydroxylation activity was remarkably high in the microsomes from 3-methylcholanthrene (3-MC)-treated rats, whereas phenobarbital (PB) treatment had a slightly enhancing effect on the N-hydroxylation of 3'-Me-DAB and a rather inhibitory effect on that of 3'-Me-MAB. Either NADPH or NADH was effective for the N-hydroxylation of 3'-Me-MAB, though the former was slightly more effective. For the reaction of 3'-Me-DAB the effect of NADPH and NADH was additive, but this was not the case for 3'-Me-MAB. Carbon monoxide, metyrapone and 2-diethylaminoethyl-2,2-diethylvalerate hydrochloride (SKF-525-A), inhibitors of cytochrome P-450, had no inhibitory effect on the N-hydroxylation of 3'-Me-DAB and 3'-Me-MAB. On the other hand, alpha-naphthoflavone, an inhibitor of cytochrome P-448, considerably inhibited the N-hydroxylation of these aminoazo dyes. In the case of partially purified mixed function amine oxidase (MFAO), 1-(1-naphthyl)-2-thiourea, an inhibitor of MFAO, completely inhibited the N-hydroxylation of 3'-Me-MAB as well as the N-oxidation of dimethylaniline. On the other hand, in a microsomal system the inhibition of the N-hydroxylation was at most 40% at the concentration giving complete inhibition of the N-oxidation of dimethylaniline. From these results, it is concluded that, in addition to MFAO, cytochrome P-448 is involved in the N-hydroxylation of MAB.

Animals↗
PubMed1982

The effect of ovariectomy on excretion of urinary steroids and tumor growth in rats bearing 7,12-dimethylbenz[a]anthracene-induced mammary cancer.

The relation between the excretion of urinary steroids and the therapeutic effect of ovariectomy on tumors was investigated in female Sprague-Dawley rats bearing 7,12-dimethylbenz[a]anthracene-induced mammary cancer. Ovariectomy significantly reduced the excretion of urinary androgen, 11-deoxy-17-oxosteroid (11-DOOS), but hardly affected that of urinary corticosteroid, 17-deoxy-corticosteroid (17-DOCS). The responsiveness of tumors to ovariectomy was positively correlated with both pre-operative 11-DOOS and pre-operative ratio of 11-DOOS to 17-DOCS, and negatively correlated with pre-operative 17-DOCS. The extent of tumor regression after ovariectomy was associated with the decrease of urinary androgen. A similar correlation was observed between the decrease in the ratio 11-DOOS/17-DOCS and tumor suppression during cyclophosphamide treatment (medical ovariectomy). These results indicated that the tumor response to ovariectomy was related to a shift of the endogenous hormone balance from a relative dominance of androgen to relative dominance of corticosteroid. The significance of the hormonal findings is discussed in the light of the steroid metabolism in human breast cancer.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1982

[A study of combination chemotherapy with cis-diamminedichloroplatinum for advanced genitourinary carcinoma].

The patients with advanced testicular tumors and bladder carcinoma were treated by combination chemotherapies including cis-diamminedichloroplatinum. Four patients with advanced testicular tumors were treated with a combination chemotherapy, consisting of cis-diamminedichloroplatinum, vinblastine, and bleomycin or pepleomycin according to Einhorn's regimen. Three patients with advanced bladder carcinoma were treated with a combination chemotherapy consisting of cis-diamminedichloroplatinum, cyclophosphamide, and adriamycin according to Yagoda's regimen. These chemotherapy regimens produced 25% complete and 75% partial responses in testicular tumors and 100% of no change in bladder carcinoma. Although an overall response rate of three patients with bladder carcinoma was 0%, one patient was plateaustable for more than three months. We believe that the combination chemotherapy including cis-diamminedichloroplatinum is promising in the management of patients with advanced testicular tumors or bladder carcinoma.

Adolescent↗
PubMed1982

[Experiences with intravenous drip infusion therapy of amikacin for severe infections in patients of hematological disorder].

Amikacin was studied for clinical effect in 7 patients with acute leukemia, 1 patient with chronic myelogenous leukemia-blastic crisis, 1 patient with malignant lymphoma and 1 patient with aplastic anemia, who were suffered from severe infection such as sepsis, pneumonia or subcutaneous abscess. Most of these patients had bleeding tendency, so amikacin was administered by intravenous drip infusion in a dose of 200 mg--400 mg for 1 hour. Total doses of amikacin were between 3.2 g and 12.6 g. These doses of amikacin gave good response to 3 patients with sepsis, 1 patient with subcutaneous abscess and 1 patient with pneumonia. We didn't observe any side effect most likely associated with amikacin. Therefore, intravenous drip administration of amikacin might be useful drug for management of severe infections in patients of hematological disorder, and seemed to be as safe as intramuscular administration.

Adolescent↗
PubMed1982

Influence of corticosteroid hormones on the therapeutic efficacy of cyclophosphamide.

The purpose of this investigation was to clarify the relation between the therapeutic efficacy of cyclophosphamide and the activity of the endogenous and exogenous corticosteroid hormones using ICR female mice with ascitic Ehrlich tumor. A single ip injection of the drug, 3 mg/mouse, was given to each mouse 36 hr after tumor inoculation (1 X 10(6) tumor cells, ip), and the drug effect was assessed in terms of the number of 1-month survivors with and without tumor. The clock time of drug administration which produced minimal therapeutic efficacy chronologically coincided with the dark period (8 PM approximately 8 AM) and/or with a stage of increased plasma corticosterone in mice. In support of this, concomitant administration of corticosterone (hydrocortisone or corticosterone) significantly depressed the anti-tumor effect of the drug. Evidence is presented to indicate that the adverse effect of corticosteroids is related to an accelerated metabolism of cyclophosphamide within the host. The drug effect for a given total dose was improved by the use of hourly partitioned injections in place of a single injection. It was concluded that the therapeutic efficacy of cyclophosphamide is dependent on the time of exposure to drug action on the scale of hours, but not days, and that the anti-tumor effect of the drug can be suppressed by increased activity of endogenous and exogenous corticosteroid hormones through acceleration of the drug metabolism.

Adrenal Cortex Hormones↗
PubMed1981

Dissociation of chorioadenoma destruens from hydatidiform mole by urinary steroid analysis.

Dissociation between hydatidiform mole (HM) and chorioadenoma destruens (CA) was attempted by gas chromatographic analysis of urinary steroids. In the chromatogram, fraction 2 (F2) including four pregnane steroids (17-hydroxypregnanolone, pregnanolone, pregnanediol, and pregnanetriol) reflected the biologic activity of molar human chorionic gonadotropin (hCG), and the ratio of F2 to fraction 1 (F1) (17-ketosteroids) was found useful in monitoring secondary growth of trophoblastic tumor: Urinary log F2/F1 after curettage declined quickly and unidirectionally in HM, but the same parameter exhibited a temporal rise in CA at 11 to 20 days after curettage because of the molar hCG from residual tumor tissue. The resolution between HM and CA at that stage (11 to 20 curettage days) was of the order of diagnostic use and superior to that with immunoreacive hCG. The data obtained are discussed in the light of pathophysiology of CA.

17-Ketosteroids↗
PubMed1981

Aarskog syndrome with isolated growth hormone deficiency.

A 5-year-old male with the Aarskog syndrome is described. He had abnormal facies, short stature, short fingers with interdigital webbing, a saddle type scrotum and mild mental retardation. In addition, he had isolated growth hormone deficiency as evidenced by the insulin, arginine, and propranolol-glucagon tests. An arginine test after short-term stimulation with estrogen further supported this diagnosis. His mother had minor abnormalities of the hands and feet, and slight mental retardation.

Child, Preschool↗
PubMed1981

Primary myelofibrosis with myeloid metaplasia and cytogenetically abnormal clones in 2 children with Down's syndrome.

2 children with Down's syndrome showed severe anaemia, leucocytosis with blastic cells, thrombocytopenia and hepatosplenomegaly. Bone marrow aspirations were near-dry tap and marrow biopsy revealed primary myelofibrosis with myeloid metaplasia (MMM). Their course was short with a blood picture similar to that of leukaemia. They expired 2 months and 21/2 months after diagnosis, respectively. The cases were thought to represent an acute childhood variant of MMM. Cytogenetic study of circulating white cells by 24 h culture without phytophaemagglutinin stimulation revealed aneuploidy in both cases, the first case showing marked aneuploidy with a predominant karyotype of 50,XX,+8,+19,+19,+21 and the second case a mosaic of 47,XX,+G/48,XX+G,+G. The karyotype of phytohaemagglutinin stimulated lymphocytes was 47,XX,+G in both cases. These findings suggest that the abnormal karyotypes are those of circulating blastic cells which are abnormal clones of haematopoietic cells responsible for MMM. In Down's syndrome, MMM might not be so rare as reported.

Bone Marrow↗