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Biomedical subjects

M Kodama

Publications and source records attributed to M Kodama.

At least 505 records · Page 28Linked to original sources

[Cytofluorometric analysis of cell kinetics in relation to tumor growth of advanced gastric cancers].

Correlated studies on both cell kinetics in association with nuclear ploidy pattern and pathological morphology of advanced gastric cancers were carried out using DNA-RNA cytofluorometry (NIKON SPM-RF1-D) with AO stain. The results showed that advanced gastric cancers could be divided into two main groups. Group 1 (12 cases) was the diploid cell population, commonly found in Borrmann type 4 showing diffuse infiltration of cancer cells, and group II (14 cases) was characterized by polyploidization, usually found in Borrmann type 2 or 3 showing adenocarcinomas composed of markedly pleomorphic cells. In addition, we further differentiated from group II four cases of cancers which included aneuploid cells with more pronounced pleomorphism than group II, and classified them as group II'. These results suggest that cell kinetics and nuclear ploidy pattern of the advanced gastric cancers are closely related to pathological characteristics, i.e., groups I and II to undifferentiated (gastric type) and differentiated (intestinal type) carcinomas, respectively.

Adenocarcinoma↗

Disruptive effect of diethylstilbestrol on microtubules.

Diethylstilbestrol, a unique carcinogen lacking measurable mutagenic potency in Salmonella, was shown to be an inhibitor of microtubule assembly in vitro using microtubule proteins isolated from porcine brains. The effective concentration of diethylstilbestrol was 10-200 microM, as determined by viscometry, turbidity measurement, and electron microscopic analysis.

Animals↗

Enhancing effect of hydrocortisone acetate administration on the content of A-type particles in Ehrlich ascites tumor.

The incidence of intracytoplasmic A-particles was investigated in neoplastic and nonneoplastic cells of Swiss/ICR mice. The concentration of the virus-like particles decreased in the order of 1) invasive Ehrlich 4N ascites clone 1 tumor, 2) noninvasive Ehrlich 4N ascites clone 3 tumor, and 3) nonneoplastic cells of tumor-free mice. Four successive injections of hydrocortisone acetate, 1 mg/day/mouse, when administered after tumor inoculation, almost tripled the cellular content of A-particles in Ehrlich clone 1 tumor (P less than .001), whereas the same treatment given before tumor inoculation did not affect the particle content. The enhancing effect of the hormone was found to be dose-dependent (P = .0027). Possibly, hydrocortisone acetate accelerates the formation of A-particles by stimulating directly the virus-generating apparatus of clone 1 tumor cells.

Administration, Topical↗

[Spindle cell carcinoma of the penis--a case report].

Over a 2-month period, a 34-year old man with phimosis developed a pedunculated tumor, measuring 4 X 2.5 X 2 cm in his glans penis. Microscopically the bulk of the tumor was composed of spindle-shaped cells, however, at some parts of the tumor, squamous cell cysts or nests, consistent with well-differentiated squamous cell carcinoma, were noted. Atypical epithelial cells merged imperceptibly with the underlying spindle-shaped cells. The histological diagnosis of spindle cell carcinoma, an uncommon variant of squamous cell carcinoma, was made. Spindle cell carcinoma arising from the penis is very rare and only two reports are available at present.

Adult↗

[Characteristics of urinary steroid excretions in ovarian cancer patients].

We performed a case-control study to investigate the urinary steroid excretions in ovarian cancer patients. The use of gas-liquid chromatography permitted the estimation of 14 urinary steroids. Data on 139 urine specimens from 36 cancer patients were compared with those on age-matched controls. A general depression of adreno-corticosteroid excretions was consistently observed in the cancer patients as compared with the control women. The possible role of observed steroidal disorders in the genesis of ovarian neoplasia is discussed in light of the epidemiological and biological aspects of this tumor.

Adrenal Cortex Hormones↗

Caerulein, a cholecystokinin-related peptide, depresses somatic function via the vagal afferent system.

Intravenous doses of 0.5-8 micrograms/kg (0.3-4.9 nmol/kg) of caerulein, a cholecystokinin-related peptide, depressed the crossed extensor reflex response of chloralose-anesthetized rats in a dose-dependent manner. Intraventricularly administered caerulein was effective only at high doses (1-2 micrograms/animal, i.e., 0.6-1.2 nmol/animal). Cervical vagotomy completely abolished the inhibitory effect of peripherally injected caerulein. Electrical stimulation of vagal afferent nerves could simulate the caerulein effect to some extent. These results suggest that the primary site of action of peripherally administered caerulein is located in the gastrointestinal tract and thus the generated afferent vagal impulses mediate the reflex depression via the nucleus tractus solitarius and other as yet unclarified brain stem structures.

Animals↗

Purification of mixed-function amine oxidase from rat liver microsomes.

To clarify the metabolism of carcinogenic aminoazo dyes in target tissues, mixed function amine oxidase (MFAO) was purified from rat liver. The MFAO was solubilized from microsomes with Triton X in the presence of 20 glycerol and 1 mM EDTA and purified successively with DEAE Sepharose CL-6B, 2',5'-ADP Sepharose 4B and Hydroxyapatite column chromatography. The purified enzyme yielded a single protein band on sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis. The apparent molecular weight was about 59,000. When dimethylaniline (DMA) was used as a substrate, the specific activity of the enzyme fortified with NADPH was about 430 nmol DMA N-oxide formed/mg protein/min with a yield of about 15%. N-Demethylation of dimethylaminoazobenzene (DAB) with the enzyme proceeded only when iron was added to the reaction system.

Animals↗

Occurrence of saxitoxin and other toxins in the liver of the pufferfish Takifugu pardalis.

Highly toxic livers of the pufferfish Takifugu pardalis were extracted with acidic ethanol. The toxins extracted were partially purified by chromatography on Bio-Gel P-2 and then Bio-Rex 70, resulting in separation into three fractions I, II and III. ratios of total mouse units per fraction were approximately 0.1:100:0.01, respectively, with tetrodotoxin (TTX) as standard. By TLC, electrophoresis and a TTX analyzer, Fr. II was identified as TTX and, unexpectedly, Fr. III as saxitoxin, while Fr. I remains unidentified.

Animals↗

Generation of hydrogen peroxide and superoxide anion from active metabolites of naphthylamines and aminoazo dyes: its possible role in carcinogenesis.

Autoxidation of active metabolites of naphthylamine and aminoazo dyes in neutral buffer generated hydrogen peroxide (H2O2) and superoxide anion (O-.2), as detected by the titanium sulfate method and nitro blue tetrazolium method, respectively. 2-Amino-1-naphthol, 1-amino-2-naphthol, 1-amino-4-naphthol, N-hydroxy-2-aminonaphthalene, N-hydroxy-1-aminonaphthalene, N-hydroxy-4-aminoazobenzene and N-hydroxy-4-methylaminoazobenzene generated H2O2 and O-.2, whereas 1-nitrosonaphthalene, 2-nitrosonaphthalene, 1-naphtylamine, 2-naphthylamine and non-carcinogenic aminonaphthols and naphthols generated no active oxygens. Catalase and superoxide dismutase were used to identify the formation of these active oxygens. For all compounds tested except nitrosonaphthalenes, good parallelism was found between the active oxygen formation and convertibility to free radicals. These results suggest a possible role of free radicals and subsequently formed active oxygens in aromatic amine carcinogenesis.

Animals↗

Release of tetrodotoxin and paralytic shellfish poison from puffer liver by RNase.

A nontoxic high-molecular fraction was separated from the extracts of toxic liver of a puffer, Takifugu poecilonotus, by Sephadex G-50 gel filtration. This fraction became toxic when digested with RNase T2. The toxins were partially purified by activated charcoal treatment, followed by chromatography on Bio-Gel P-2 and Bio-Rex 70, and were analyzed by TLC and electrophoresis. The results showed that most of the toxicity is accounted for by tetrodotoxin, and the remainder by saxitoxin and other unidentified toxins. The corresponding high-molecular fraction separated from nontoxic liver of another puffer, T. rubripes, did not release any toxin on RNase digestion.

Animals↗

Incorporation of bile acid of low concentration into model and biological membranes studied by 2H and 31P NMR.

We have analyzed the manner of incorporation of bile acid into lipid bilayers and resultant perturbation of the bilayer structure with lower bile acid/lipid ratios relevant to the physiological conditions (approximately 1 mM) by 2H and 31P NMR methods, as an aid to understanding the possible role as an endogenous tumor promoter in colon cancer besides the primary physiological function of solubilizing lipids. On the basis of the 2H quadrupole splittings of [6,6,7,7,8-2H5]deoxycholate and [11,11,12,12-2H4]chenodeoxycholate in the presence of lamellar multibilayers of egg yolk lecithin, these bile acids were found to be incorporated in such a manner that the B-D rings lie parallel with the normal of the bilayers when the ratio of the bile acid to lipid is low (less than 0.11). When the ratio is increased, these bile acid molecules are not dispersed entirely in the bilayer but aggregate to form micelles with lipids. Further, we studied the resultant perturbation of the multibilayers of egg yolk lecithin analyzed by using the 2H quadrupole splitting of [18,18,18-2H3]stearic acid as a probe and by 31P chemical shift anisotropy. We found that the bilayer structure is retained even at the bile acid-to-lipid ratio of 0.25, although a small amount of an isotropic phase appeared such as small vesicles and micelles. The molecular ordering of fatty acyl chains was rather enhanced by the presence of 1 mM deoxycholate in erythrocyte ghosts as seen from the 2H quadrupole splitting of [16,16,16-2H3]palmitic acid, although deoxycholate caused hemolysis in this condition. The former observation can be explained by the way the lipid-protein interaction is modified by deoxycholate located in the interface between the lipids and proteins.

Animals↗

An electron spin resonance study on the free radicals produced from aclacinomycin a and its derivatives: analysis of hyperfine structure of the spectra by means of molecular orbital method.

Quinone-containing carcinostatics, aclacinomycin A and its derivatives were investigated on the convertibility to free radical under a mild reducing condition. The hyperfine structures of electron spin resonance (ESR) spectra were satisfactorily reproduced by computer simulations, using the hyperfine coupling constants calculated by the Intermediate Neglect of Differential Overlap Molecular Orbital (INDO MO) method. This verifies the reliability of molecular orbital calculations and opens a way to analyze theoretically the correlation between chemical structures and carcinostatic activities. By analyzing hyperfine structures of ESR spectra, the free radical produced from aclacinomycin was identified as a neutral form of semiquinone radical of intact aclacinomycin. Taking into account the previous finding that 7-deoxyaklavinone (C1) is formed reductively by cytochrome P-450 reductase (EC 1.6.2.4; Komiyama et al., 1979), it is postulated that two types of semi-quinone radicals exist in vivo.

Aclarubicin↗

Classification of compounds by cluster analysis of Ames test data.

The dose-response curves for various compounds in the Ames test were analyzed by combining the least-squares method with cluster analysis. The following theoretical equation was employed: m(x) = (B + Sx)exp(-Tx), where m(x) is the number of revertants at the dose of x; B, the background number; S, the mutagenicity rate; and T, the toxicity rate. This equation is derived from a one-hit model modified to take account of the toxicity, and the parameters B, S and T are determined by applying the least-squares method for the fitting between theoretical and experimental dose-response curves with the use of the program package SALS (statistical analysis with least-squares fitting). With the values for B, S and T thus obtained, cluster analysis can clearly separate mutagenic and non-mutagenic compounds. Moreover, when cluster analysis into six groups is carried out, each group has quite characteristic parameter values. Consequently, this procedure is very useful for the classification of compounds according to the nature of the dose-response curve, that is, according to the nature of their mutagenic activity.

Carcinogens↗