[Determining the of intraocular tumors using calipers and combined A and B image echography].
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Biomedical subjects
Publications and source records attributed to J Graw.
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A spontaneous mutation causing a nuclear opacity of the lens of the eye was detected among (101 X C3H) F1 hybrid mice. The nuclear opacity, provisional gene symbol Nop, is inherited as a single autosomal dominant gene. Penetrance on the genetic background of the 101-strain is complete. Heterozygotes and homozygotes are viable and fertile. The amount of protein after centrifugation at 3000 g is reduced in the cataractous lens. After isoelectric focusing a band at pH 8.5 in the protein pattern is missing. The glutathione redox-state of the cataractous lens is also affected. The amount of oxidized glutathione relative to the total amount of glutathione is increased from 2.7 to 7.8% in the Nop/ + mutant (P less than 0.01). Enzyme activities connected with the glutathione redox-cycle (glutathione peroxidase, glutathione reductase, glucose-6-phosphate dehydrogenase) are not affected. The activities of some glycolytic enzymes, phosphoglycerate kinase, glyceraldehyde-phosphate dehydrogenase, phosphoglyceromutase and triosephosphate isomerase are reduced (P less than 0.05). However, the concentration of ATP in the cataractous lens is unchanged.
A gamma-crystallin has been purified by a two-step column chromatography from an extract of water soluble lens proteins from (101/ E1xC3H /E1)F1 mice. About 17% of the water soluble lens protein in normal mice is represented by this gamma-crystallin. The protein has been shown to be absent in cataractous lenses of Nop /+ mice after isoelectric focusing of water soluble lens proteins. It has a MW of 20,000. Amino acid analysis reveals the occurrence of eight cystein residues, which is considered to be high compared to other crystallins. The protein might play an important role in cataractogenesis.
An ATP-dependent deoxyribonuclease was isolated from lymphocyte nuclei. The enzyme preparation sediments with about 4 S through sucrose gradients and shows one stainable band after sodium dodecyl sulfate gel electrophoresis. We find three, possibly four, activities associated with the enzyme: a DNA-independent ATPase activity; an ATP-independent endonuclease; an ATP-dependent nuclease which degrades nicked DNA to acid-soluble material; and an unwinding activity producing single-stranded regions in nicked DNA.
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By i.p. application of 70 or 100 mg/kg ethyl-nitrosourea, resp., to gravide Göttingen miniature pigs on days 14 or 16, resp., of gestation massive malformations of the skeletal system were produced. The experiments demonstrated the teratogenic effect of ethylnitrosourea on non-rodents, ascertained the period of determination of the skeletal system in pigs, confirmed the concentration effect in teratogenesis as well as the ineffectiveness of biological barriers with adequately high dosages.
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The multiple endpoint mammalian mutagenesis approach developed in our institute screens in the same animal for recessive specific-locus alleles at 7 loci, approximately 30 loci coding for dominant-cataract mutations, 23 loci controlling protein-charge changes and 12 loci for enzyme-activity alterations. Experiments to screen for the approximately 70 loci in the same offspring of treated male mice were performed with ethylnitrosourea (ENU), procarbazine and X-ray exposure. Mutations were recovered for each genetic endpoint in all treatment groups where a sufficient number of offspring was scored. ENU treatment is highly effective in inducing mutations to all genetic endpoints. The mutations were confirmed by breeding tests. The mutation rates to specific-locus and enzyme-activity alleles were both higher than the mutation rates to either dominant-cataract or protein-charge alleles. The advantages and possibilities of the multiple endpoint approach are discussed in detail.
Male mice were X-irradiated with 3.0 + 3.0 Gy or 5.1 + 5.1 Gy (fractionation interval 24 h). The offspring were screened for dominant cataract and recessive specific locus mutations. In the 3.0 + 3.0-Gy spermatogonial treatment group, 3 dominant cataract mutations were confirmed in 15 551 offspring examined and 29 specific locus mutations were recovered in 18 139 offspring. In the post-spermatogonial treatment group, 1 dominant cataract mutation was obtained in 1120 offspring and 1 recessive specific locus mutation was recovered in 1127 offspring. The induced mutation rate per locus, per gamete, per Gy calculated for recessive specific locus mutations is 2.0 X 10(-5) in post-spermatogonial stages and 3.7 X 10(-5) in spermatogonia. For dominant cataract mutations, assuming 30 loci, the induced mutation rate is 5.0 X 10(-6) in the post-spermatogonial stages and 1.1 X 10(-6) in spermatogonia. In the 5.1 + 5.1-Gy spermatogonial treatment group, 3 dominant cataract mutations were obtained in 11 205 offspring, whereas in 13 201 offspring 27 recessive specific locus mutations were detected in the spermatogonial group. In the post-spermatogonial treatment group no dominant cataract mutation was observed in 425 offspring and 2 recessive specific locus mutations were detected in 445 offspring. The induced mutation rate per locus, gamete and Gy in spermatogonia for recessive specific locus mutations is 2.8 X 10(-5) and for dominant cataract mutations 0.9 X 10(-6). In post-spermatogonial stages, the mutation rate for recessive specific locus alleles is 6.2 X 10(-5). In the concurrent untreated control group, in 11 036 offspring no dominant cataract mutation and in 23 518 offspring no recessive specific locus mutation was observed. Litter size and the number of carriers at weaning have been determined in the confirmation crosses of the obtained dominant cataract mutants as indicators of viability and penetrance effects. Two mutants had a statistically significantly reduced litter size and one mutant had a statistically significantly reduced penetrance.