[Morphological analysis of congenital craniofacial malformations].
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Biomedical subjects
Publications and source records attributed to N Motohashi.
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The labeling reactions of L-lysine and poly-L-lysine (average of molecular weight: 3400 (I), 15000 (II), 25000 (III) and 87000 (IV) with 57Co2+ ions and the tumor and organ distributions of their complexes were examined. L-Lysine and poly-L-lysine with 57Co2+ ions were incubated for 20 hrs at 30 degrees C in the solution of pH 9.0 and 50 v/v% ethanol solution of pH 10.5, respectively. L-Lysine and poly-L-Lysine were labeled with 57C02+ ions in radiochemical yields of over 95 and 60-70%, respectively. The radioactive polypeptides were separated from unreacted 57Co2+ ions in the range of pH 8.0 to 8.5 by means of gel filtration on Sephadex G-25 M column (1.5 X 5.0 cm). The radioactive complexes were injected intravenously in mice. L-Lysine complex was excreted rapidly from tumour tissue and various organs. The localization of poly-L-lysine complexes in tumor was higher 3 to 5 times than that of L-lysine complex at 20 hrs after injection. The localization in tumor increased in the order of L-lysine-less than II-less than I-complex. II-Complex was excreted scarcely from tumor. 57Co-poly-L-lysine complexes revealed remarkably high localization in liver and spleen. THe localization in tumor of those complexes seemed to be related to the molecular weight and the positive charge of lysine.
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Two male patients with Johanson-Blizzard syndrome are presented. Radiocephalometry of the craniofacial complex disclosed findings previously unreported. The radiographic observations, extending from age 6 months to 5 years of age in one case, revealed a decelerating growth pattern with minimal effect on the neurocranium, but with greater effect on facial growth. Maxillary growth was more severely retarded than mandibular growth. The phenotypic characteristics related to growth retardation are age dependent in the severity of their expression.
Roentgencephalometric investigation of four patients (three male, one female) with cerebral gigantism (Soto syndrome) demonstrated that both the neurocranium and facial skeleton are increased in size. The recessed flat facies characteristic of the syndrome can be attributed to the increased anterior cranial base length and frontal bossing combined with relative retroposition of the maxilla. Mandibular body length was increased but ramal height was within normal limits. The obtuse gonial angle added to the effective length of the mandible. The backward rotation of the mandible resulting from the obtuse gonial angle contributed to increased lower face height.
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Benz[c]acridine and its 10 methyl-substituted derivatives were examined for chemical reactivity with osmium tetroxide and mutagenic activity on Salmonella typhimurium, and the results were contrasted with the electronic charge in the K region and the carcinogenic activity of benz[c]acridines. The addition of osmium tetroxide took place at the K region of benz[c]acridines. A linear relationship was established between the charge in the K region and the rate constant of the second-order reaction between osmium tetroxide and benz[c]acridines except the 5,7-dimethyl derivative whose substituent in the 5-position sterically hindered the reaction. Benz[c]acridines showed mutagenic activity in the presence of S-9 Mix, but not in the absence of S-9 Mix. There was a corresponding relationship among the K-region reactivity, mutagenic activity, and carcinogenic activity in benz[c]acridines. The only exception for this was the 7,11-dimethyl derivative in which the 11-methyl group had a steric effect on the ring-nitrogen atom. It was suggested that a common mechanism with regard to the reactivity of the K region is working in both carcinogenesis and mutagenesis. It was concluded that benz[c]acridines are activated, before they display a carcinogenic or mutagenic activity, to a proximate form such as 5,6-epoxides, through a metabolic process in which the nucleophilic property of the K region to react with electrophilic reagents plays an important role.
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Formation of a free radical from carcinogenic and noncarcinogenic benz[c]acridine derivatives in the presence of proteins was examined. When aqueous mixture of benz[c]acridine and protein was stirred for a long period, shielded from light, benz[c]acridines were converted into free radicals. Albumin had the greatest effect in accelerating the free radical formation, and the effect was smaller in globulin, histone, and deoxyribonuclease. The g-value of the free radicals thus obtained was 2.005. Intensity of the electron spin resonance (ESR) signals of the free radical from carcinogenic derivatives was higher than those of the free radical from noncarcinogenic derivatives. There was a corresponding correlation among the ESR signal intensity of the free radical formed from the mixed system of benz[c]acridine and protein, charge of the K-region or ring nitrogen of the compound, and carcinogenicity of benz[c]acridines.
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