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Biomedical subjects

A Ito

Publications and source records attributed to A Ito.

At least 973 records · Page 54Linked to original sources

Effect of age at treatment on the incidence and location of neurogenic tumors induced in Wistar rats by a single dose of N-ethyl-N-nitrosourea.

The effect of age at treatment on the incidence and location of neurogenic tumors induced by N-ethyl-N-nitrosourea (ENU) was investigated in 232 Wistar rats of both sexes. Rats were given 40 ng/kg of ENU on the 16th day of gestation (group I), on the day of birth (group II), and on the 1st week (group III), 2nd week (group IV), 3rd week (group V) and 4th week (group VI) after birth. Up to 6 months of observation, the brain consistently showed the highest susceptibility ranging from group I (93%) to group VI (36%), followed by the spinal cord (group I, 34%; group II, 64%; group III, 43%). However, the trigeminal nerve was only susceptible in group I (27%) and group II (36%) and the spinal root was susceptible exclusively in group II (46%). Most of the tumors obtained were oligodendrogliomas or mixed gliomas. Glioependymomas of the spinal cord were predominant only in group II. The temporal and paraventricular regions and hippocampus were the preferred sites of brain tumors in group I and II, but in groups III and IV frontal tumors were predominant. Mesenchymal tumors of the kidney were also induced, mainly in groups III (16%) and IV (16%).

Age Factors↗

Partial purification and characterization of a novel neutral proteinase from human uterine cervix.

1. Human uterine cervical stroma was found to contain a Ca(2+)-independent neutral proteinase against casein and N-benzoyl-dl-arginine p-nitroanilide (Bz-dl-Arg-Nan). This enzyme was tightly bound to an insoluble material (20000g pellet) and was solubilized by high concentrations of NaCl or KCl. High concentrations of them in the reaction system, however, inhibited reversibly the activity of this enzyme. 2. The neutral proteinase was partially purified by extraction with NaCl, gel filtration on Sephadex G-200 and affinity chromatography on casein-Sepharose. 3. The optimal pH of this partially purified enzyme was 7.4-8.0 against casein and Bz-dl-Arg-Nan. The molecular weight of the enzyme was found to be about 1.4x10(5) by gel filtration on Sephadex G-200. 4. The enzyme was significantly inhibited by di-isopropyl phosphorofluoridate (0.1mm). High concentration of phenylmethanesulphonyl fluoride (5mm), 7-amino-1-chloro-3-l-tosylamidoheptan-2-one (0.5mm), antipain (10mum) or leupeptin (10mum) was also found to be inhibitory, but chymostatin (40mug/ml), soya-bean trypsin inhibitor (2.5mg/ml), human plasma (10%, v/v), p-chloromercuribenzoate (1mm), EDTA (10mm) and 1-chloro-4-phenyl-3-l-tosylamidobutan-2-one (1mm) had no effect on the enzyme. 5. The neutral proteinase hydrolysed casein, Bz-dl-Arg-Nan and heat-denatured collagen, but was inactive towards native collagen and several synthetic substrates, such as 4-phenylazobenzyloxycarbonyl-Pro-Leu-Gly-Pro-d-Arg, 3-carboxypropionyl-Ala-Ala-Ala p-nitroanilide and 2,4-dinitrophenyl-Pro-Gln-Gly-Ile-Ala-Gly-Gln-d-Arg, and also proteoglycan. The enzyme did not act as a plasminogen activator. 6. These properties suggested that a neutral proteinase in the human uterine cervix was different from enzymes previously reported.

Adult↗

Unusual histiocytic tumor of the small intestine.

A case of unusual sarcoma of the small intestine is described. Ultrastructural observation, enzyme histochemical studies, and functional analysis, such as phagocytic capacity and surface markers, were helpful in defining the neoplastic cells as histiocytes. Autopsy findings are presented.

Histiocytoma, Benign Fibrous↗

Mammary carcinogenic effect of low-dose fission radiation in Wistar/Furth rats and its dependency on prolactin.

The mammary carcinogenic effect in rats of low-dose fission radiation and its dependency on prolactin were studied. A total of 141 female W/Fu rats were exposed to 4.8, 8.9, or 19.5 rads of fission radiation that had both fision neutrons of 2.0 million electron volts (MeV) and gamma ray components similar to those produced by the Hiroshima bomb. Only 1 of 48 rats (2.0%) developed mammary tumor (MT) after irradiation alone, whereas 20 of 48 rats (41.6%) developed MT's if prolactin was supplied shortly after irradiation by means of grafting of the prolactin-secreting pituitary tumor. Furthermore, MT's occurred in 11 of 45 rats (24.4%) treated with prolactin as late as 12 months after irradiation, which suggested the long-term survival of radiation-induced dormant MT cells. A correlation was found between the development of MT and the elevation of serum prolactin level; most MT's appeared shortly after the grafted mammotropic pituitary tumor became palpable. The growth of MT's appeared to be promoted by prolactin in collaboration with ovarian hormones; the growth of adenocarcinomas was dependent on prolactin and ovarian hormones, whereas the growth of fibroadenomas appeared to be less hormone-dependent. Much higher biologic effectiveness, especially in the low-dose range, was found with 2.0-MeV fission neutrons compared with 14.1-MeV fast neutrons or 180-kilovolt peak X-rays in rat mammary carcinogenesis.

Adenocarcinoma↗

Cytochrome b5-like hemoprotein of outer mitochondrial membrane; OM cytochrome b. I. Purification of OM cytochrome b from rat liver mitochondria and comparison of its molecular properties with those of cytochrome b5.

A cytochrome b5-like hemoprotein associated with the outer membrane of rat liver mitochondria, OM cytochrome b, was purified to homogeneity after solubilization with trypsin. OM cytochrome b was separated from microsomal cytochrome b5 by hydroxylapatite chromatography, though they were indistinguishable in DEAE-cellulose chromatography and in Sephadex G-75 gel filtration. The absorption spectra of reduced OM cytochrome b and cytochrome b5 in the visible region at liquid nitrogen temperature showed small but significant differences between them. A clear difference was also detected in amino acid composition, particularly in the contents of basic amino acids and methionine. Using rabbit antibodies prepared against purified OM cytochrome b and cytochrome b5, immunochemical comparison was also carried out. No immunological cross reaction was observed by Ouchterlony double diffusion in agar gel or in a quantitative immunoprecipitation test. It is thus concluded that OM cytochrome b is distinct from microsomal cytochrome b5.

Animals↗

Cytochrome b5-like hemoprotein of outer mitochondrial membrane: OM cytochrome b. II. Contribution of OM cytochrome b to rotenone-insensitive NADH-cytochrome c reductase activity.

The participation of OM cytochrome b in the rotenone-insensitive NADH-cytochrome c reductase activity of rat tissues was investigated in comparison with that of cytochrome b5, by using antibodies against these two cytochromes. The specificity of each antibody was confirmed by inhibition studies of NADH-cytochrome c reductase activities reconstituted from purified cytochromes and NADH-cytochrome b5 reductase. OM cytochrome b-mediated NADH-cytochrome c reductase activity was found in various tissues including liver, kidney, heart, and brain. The contribution of this activity to the total rotenone-insensitive NADH-cytochrome c reductase activity was high in heart and brain cells. NADH-cytochrome c reductase activity mediated by OM cytochrome b was principally localized in mitochondrial outer membrane. Immunoadsorption studies using antibody-coated polyacrylamide beads showed that significant OM cytochrome b-mediated activity is present in the microsomal membrane, and that cytochrome b5-mediated activity also exists in the mitochondrial outer membrane.

Animals↗

The existing forms of collagenase in the human uterine cervix.

The existing forms of collagenase [EC 3.4.24.7] in the human uterine cervix were examined. The latent collagenase extracted by homogenization in 0.25% Triton X-100 containing 0.01 M CaCl2 was indicated to be a complex of collagenase with alpha 2-macroglobulin by the behavior of the fraction of this enzyme before and after treatment with NaSCN on Sephadex G-150 column chromatography and an immunodiffusion method. The active collagenase was extracted by rehomogenization in 50 mM Tris-HCl buffer, pH 7.4, containing 0.1 M M CaCl2 from the insoluble residue at 0 degrees C. Another latent collagenase was extracted from the insoluble fraction in the same buffer by heating at 60 degrees C for 4 min and this enzyme was activated by 4-aminophenylmercuric acetate or trypsin. The molecular weights of the active and the latent forms were approximately 7.3 x 10(4) and 9.4 x 10(4), respectively. This indicates that the latency is due to the formation of a low molecular weight inhibitor enzyme complex. These results clarified that the human uterine cervix contains three existing forms (alpha 2-macroglobulin complex, active form and low molecular weight inhibitor complex) of collagenase under these experimental conditions.

Amino Acids↗

Effects of aging on hydroxyproline in human heart muscle.

Hydroxyproline concentration in the NaCl-soluble, TCA-soluble, and residual fractions of heart muscle was chemically determined in 40 autopsy subjects (25 men and 15 women), to study the effects of aging. In the left ventricle, the total hydroxyproline content of the endocardium and papillary muscle increased significantly in relation to age; the increase was greatest in the TCA-soluble fraction, followed by the residual fraction. Statistical analysis revealed that hydroxyproline in the residual fraction increased from the epicardium to the endocardium and then to the papillary muscle. Significant negative correlations were found between heart weight and total hydroxyproline in the epicardium and endocardium. In the right ventricle, a significant negative correlation was noted between heart weight and total hydroxyproline content. Though no correlations were evident between age and hydroxyproline content in females, significant correlations were observed between age and the total hydroxyproline content of the endocardium and papillary muscle in males. Furthermore, soluble collagen increased in most parts of the heart in females, but insoluble collagen increased in all parts of the heart in males. It is concluded that the hydroxyproline content of heart muscle increases in proportion to age and is in inverse proportion to heart weight. The increase occurs in the TCA-soluble and residual fractions, and extends from the endocardium to the papillary muscle. More profound changes in collagen metabolism are observed in males.

Adult↗

In vitro antibacterial activity of AM-715, a new nalidixic acid analog.

AM-715 [1-ethyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylic acid] is a new nalidixic acid analog. AM-715 has a broad spectrum of antibacterial activity against gram-positive and gram-negative bacteria. The antibacterial activity of AM-715 was greater than those of pipemidic acid and nalidixic acid. AM-715 had higher antibacterial activity against Pseudomonas aeruginosa than did gentamicin. Most nalidixic acid-resistant bacteria were susceptible to AM-715, and cross-resistance was not observed between AM-715 and various antibiotics. The minimal concentration of AM-715 required to inhibit the growth of 75% of the total number of clinical isolates was as follows: Escherichia coli, 0.04 mug/ml; Klebsiella pneumoniae, 0.1 mug/ml; Serratia marcescens, 0.88 mug/ml; Enterobacter spp., 0.076 mug/ml; Staphylococcus aureus, 1.10 mug/ml; P. aeruginosa, 0.38 mug/ml; and nalidixic acid-resistant strains of gram-negative bacteria, 0.62 mug/ml. AM-715 at minimal inhibitory concentrations or at slightly higher concentrations had bactericidal activity against various species of bacteria. The effect of inoculum sizes on minimal inhibitory concentrations and minimal bactericidal concentrations of AM-715 against gram-negative bacteria was smaller than on those of pipemidic acid and nalidixic acid. The dose-response curve of AM-715 indicated a steep gradient, and the 50% inhibited doses of AM-715 were 0.014 mug/ml against E. coli ML4707 and 0.21 mug/ml against P. aeruginosa NC-5.

Anti-Bacterial Agents↗

Synergism of diethylstilbestrol and other carcinogens in concurrent development of hepatic, mammary, and pituitary tumors in castrated male rats.

Castrated male WF rats, given implants of pellets containing 5.0 mg diethylstilbestrol (DES), were given N-butyl-N-nitrosourea (NBU) in small amounts, which alone produced no mammary tumors in intact female rats. Treatment resulted in the high yield of hepatic tumors (HT), mammary tumors (MT), and pituitary tumors (PT) concurrently in each rat. If animals were further treated with prolactin, the development of HT and MT was accelerated, whereas that of PT was suppressed. None of the intact or castrated rats receiving NBU and/or prolactin developed tumors in any tissues if DES treatment was omitted. Exposure of male rats, preconditioned similarly to NBU treatment, to 200 rads of 14.1-MeV fast-neutron radiation also elicited HT, MT, and PT with an efficiency comparable to that of NBU-treated rats. These findings indicate that DES played an essential role in the whole carcinogenic process in each tissue and that castrated male rats, if conditioned properly with estrogens, are useful for the study of the carcinogenesis mechanism in these tissues.

Animals↗