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Biomedical subjects

E C Miller

Publications and source records attributed to E C Miller.

At least 91 records · Page 5Linked to original sources

DNA adducts formed from N-benzoyloxy-N-methyl-4-aminoazobenzene in vitro and from N, N-dimethyl-4-aminoazobenzene in mouse liver.

Reaction of N-benzoyloxy-N-methyl-4-aminoazobenzene with (14C) deoxyguanosine yielded a series of at least 10 dye derivatives separable by high-performance liquid chromatography. The major adduct, N-(deoxyguanosin-8-yl)-N-methyl-4-aminoazobenzene, was present as both cis and trans isomers. Similar series of adducts were obtained from enzymatic digests of DNA reacted in vitro with N-benzoyloxy-N-methyl-4-aminoazobenzene or from hepatic DNA of (C57BL/6 x C3H/He)F, males given injections at 12 days of age of [prime ring-(3)H]N, N-dimethyl-4-aminoazobenzene. The concentrations of the major adduct and of the second most prominent adduct in the hepatic DNA, after correction for liver growth, were approximately 30 to 70% of the initial values after 10 days; thus the second adduct was poorly removed in comparison to the major adduct.

Animals↗

Estimation of apurinic/apyrimidinic sites and phosphotriesters in deoxyribonucleic acid treated with electrophilic carcinogens and mutagens.

The number of apurinic/apyrimidinic (AP) sites in supercoiled SV40 deoxyribonucleic acid (DNA) after treatment with several electrophilic mutagens was quantitated by electrophoretic analysis of the DNA after cleavage of the phosphodiester bonds adjacent to AP sites by a specific endonuclease. The compounds studied, in order of increasing yields of AP sites obtained on incubation with the DNA for 5 h at 37 degrees C, were dimethylcarbamoyl chloride, ethyl methanesulfonate, N-ethyl-N-nitrosourea, 2-(N-acetoxyacetylamino)fluorene, beta-propiolactone, N-methyl-N-nitrosourea, methyl methanesulfonate, 1'-acetoxyestragole, 4-(N-acetoxyacetylamino)stilbene, (+/-)-7 beta, 8 alpha-dihydroxy-9 alpha, 10 alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene, N-(benzoyloxy)-N-methyl-4-aminoazobenzene, and 1-pyrenyloxirane. After a 5-h incubation at 37 degrees C and extraction of unreacted compound, further incubation at 70 degrees C generally increased the yield of AP sites; an exception was N-(benzoyloxy)-N-methyl-4-aminoazobenzene-reacted DNA. Except for DNA treated with N-ethyl-N-nitrosourea and N-methyl-N-nitrosourea, which are known to bind to a significant extent to DNA phosphates, the number of alkali-labile lesions in the treated DNA was similar to the number of AP sites. For the compounds studied there was no direct correlation between the number of AP sites produced and missense mutagenic activity, as measured in Salmonella typhimurium strain TA100.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗

[The problem of the increased perinatal mortality in premature breech deliveries, compared to premature vertex deliveries (author's transl)].

The perinatal mortality of 115 premature breech deliveries is compared to that of 843 vertex deliveries. No difference is found when birth weights at 100 gram intervals are compared. These results are statistically checked. The authors show that comparisons at 500 gram intervals are insufficient and can lead to wrong conclusions. When all premature deliveries without birth weight groups are compared the contrary results are statistically very significant. These results are in concordance with the perinatal mortality figures of mature infants born by various methods. The investigations lead to the conclusion that the mode of delivery has no essential influence on the neonatal prognosis. Mere breech presentation by itself is no indication for different delivery than for all premature deliveries. It is not so important to treat the breech presentation as it is to prevent premature deliveries.

Berlin↗

Comparative carcinogenicities of 4-N-pyrrolidinylazobenzene, its 4'-ethyl derivative, N-methyl-5-phenylazoindoline, and N,N-dimethyl-4-aminoazobenzene in the rat.

Ashby et al. (Carcinogenesis 1:1-7, 1980) have reported that 4-N-pyrrolidinylazobenzene is a powerful toxin and transforming agent in BHK cells. They have also proposed a scheme for the prediction of carcinogenic activity which is based on structural analysis of this and other compounds, including N-methyl-5-phenylazoindoline, tested in their BHK system. Contrary to their prediction, we found that 4-N-pyrrolidinylazobenzene and N-methyl-5-phenylazoindoline were not carcinogenic when fed to adult rats under conditions where N,N-dimethyl-4-aminoazobenzene induced a high incidence of hepatic carcinomas. 4'-Ethyl substitution of the pyrrolidine derivative yielded a weak carcinogen. These data suggest that complex structure-activity analyses for carcinogenic activity in this class of compounds are premature in the absence of data on whole animals. The transformation of BHK cells appears to require further validation as a predictor of the carcinogenic activity of chemicals for animals.

Animals↗

[Ultrasonic biometry for foetal weight determination (author's transl)].

A new formula has been derived from computer-aided analysis for predictive calculation of foetal weight. Biparietal diameter and mean thorax diameter were the parameters for measurement, while the truncus was additionally included for another method by which even higher demands could be met. Weight determination proper was based on a practicable vanishing point diagram (nomogram). -- A critical appraisal is made of the methods previously used for weight forecasting on the basis of ultrasonic biometry. The authors' own approach is described in great detail and for convenient check-up by means of mathematical tables and graphs. It is claimed to give better results, particularly in marginal areas of foetal development, such as hypertrophy and/or macrosomia in concomitance with diabetes mellitus or retardation. -- Data published by other authors were recalculated, with the view to producing hard evidence to the superiority of the new formula.

Anthropometry↗

[Studies into specificity for dye test (DT), complement fixation (CF), and intradermal test (ST) in diagnosis of toxoplasmosis (author's transl)].

Reference is made to an earlier study into the usefulness of the intradermal test. Now, an account is given of the specificities of tests used at present for the detection of toxoplasmosis, with reference being made to 4,341 intradermal tests, 1,332 dye tests, and 880 complement fixations. -- The three methods are qualitatively and quantitatively compared in great detail, with the close correlations between them explained. Reference is also made to the different origins of the antibody types detectable by the methods concerned. -- It seems to be quite obvious that the production of those antibody types differs in time and site, just as their lives are different in length. These findings actually are used as a point of departure for more detailed methodical proposals that should be followed in the search for an acute infection with Toxoplasma gondii. -- Various effects which might lead to unspecific tests are described in some length. -- All the above studies and findings have been used to compile a diagnosis diagram which may be a good basis for clinical decision-making on therapy.

Complement Fixation Tests↗

[Behaviour of cellular immunity, detectable by means of intradermal test, following Toxoplasma gondii infection (author's transl)].

The percentage of strongly positive reactions to intradermal testing of 2,997 pregnant women was found to grown continuously by about one per cent per annum along with growing age. -- The conclusion drawn from comprehensive discussion of the above findings is that cellular immunity is likely to grow rather than decline, as assumed in the past, following toxoplasmosis infection. However, the increase, about one per cent annually, is of minor dimensions and might be based on a booster effect. -- This would mean, after all, that the intradermal test will continue to be of informative value, even long time after the infection, for example, in the context of aged patients. Therefore, no correction is required either by the criteria of interpretation.

Adolescent↗

[Perinatal mortality of newborns with birth weights above 2,500 g and delivered from breech presentation (author's transl)].

An account is given of the problem of delivery from breech presentation, with reference being made to an analysis of childbirths over the last 14 years (1965 through 1978). -- Since the rate of premature births from breech presentation was found to be much higher than that generally recordable from vertex presentation, the gap being roughly by factor 4, reference in this paper has been restricted to children with birth weights above 2,500 g, defined as "mature" in a WHO recommendation, with the view to establish comparability between the data given in this paper, on the one, hand and the birth record on the basis of vertex presentation, on the other. -- Evidence is provided, by the example of 604 newborns delivered from breech presentation, that their intrapartum and postpartum mortality -- generally referred to as "purified" perinatal mortality, does not differ from figures quoted for comparable cases of vertex presentation. -- Another point made is that the vaginal route of delivery, except for complete extraction, is by no means necessarily inferior to caesarean section. Reduction of perinatal mortality, including morbidity, is considered to depend primarily on adequate labour monitoring. -- Taking into due consideration the considerable increase in maternal mortality and morbidity, the authors feel that the indications followed for termination of labour by caesarean section should be identical with those applicable to vertex presentation. -- The conclusion is drawn that delivery from breech presentation is a problem of premature birth rather than of positional abnormality.

Birth Weight↗

Adducts from the reaction of N-benzoyloxy-N-methyl-4-aminoazobenzene with deoxyguanosine or DNA in vitro and from hepatic DNA of mice treated with N-methyl- or N,N-dimethyl-4-aminoazobenzene.

N-Benzoyloxy-N-methyl-4-aminoazobenzene, a synthetic model ultimate carcinogenic derivative of N-methyl- and N,N-dimethyl-4-aminoazobenzene, reacted with [8-14C]deoxyguanosine in vitro to yield ten 14C-containing products separable by high-performance liquid chromatography. N-(Deoxyguanosin-8-yl)-N-methyl-4-aminoazobenzene, previously characterized as the major adduct formed in this reaction, occurred as cis and trans isomers which were interconvertible and together accounted for 75% of the reaction of N-benzoyloxy-N-methyl-4-aminoazobenzene with [8-14C]deoxyadenosine. The products obtained by reaction of DNA with N-benzoyloxy-N-methyl-4-aminoazobenzene and subsequent digestion to deoxynucleosides had a profile similar to that of the products obtained from deoxyguanosine except that the DNA digest contained a second major product that was formed in only small amounts on reaction with deoxyguanosine. The latter product has been identified as 3-(deoxy-guanosin-N2-yl)-N-methyl-4--aminoazobenzene by Beland et. al. (Chem.-Biol. Interactions, in press). Reaction with [purine-14C]DNA showed that most, if not all, of the products were derived from purine nucleosides. Digests of the DNA from the livers of C57BL/6 X C3H/He F1 mice, given injections at 12 days of age with [prime ring-3H]N-methyl- or N,N-dimethyl-4-aminoazobenzene, contained the same major adducts as did those obtained from DNA reacted with N-benzoyloxy-N-methyl-4-aminoazobenzene. The hepatic DNA also yielded a series of minor products that comigrated on high-performance liquid chromatography with adducts obtained in the reactions with N-benzoyloxy-N-methyl-4-aminoazobenzene. Approximately 70 and 30%, respectively, of the N-(deoxyguanosin-8-yl)-N-methyl-4-aminoazobenzene and of the second major product were removed from the mouse liver DNA within 10 days after administration of [prime ring-3H]N,N-dimethyl-4-aminoazobenzene. These data are of interest in view of the development of multiple hepatic tumors in mice of this hybrid treated prior to weaning with N-methyl- or N,N-dimethyl-4-aminoazobenzene.

Animals↗

[Change of immunity during pregnancy (author's transl)].

Determination of antibody to toxoplasmosis, on the basis of DT, CF, and ST, has shown that antibody quantities may vary, in the course of pregnancy, but are characterised by defined behaviour.--Antibody levels are shown to be at their maximum in early gravidity, that is before the 18th week of pregnancy, followed by relative decline and widely constant values beyond the 25th week.--The author, in a comprehensive discussion, points at the similarity between curves and titres of HCG excretion in urine, and he consideres that similarity a possible approach to further studies in greater detail.--Reference is also made to the importance of the above findings to diagnosis of acute infection by Toxoplasma gondii.

Antibody Formation↗

[Prolapse of umbilical cord - new aspects (author's transl)].

In an evaluation of more than 20,000 births, 39 recorded cases of prolapse of the umbilical cord were investigated in greater detail for the risk of perinatal mortality and morbidity. Particular attention was given to several variants of breech presentation in comparison to vertex presentations as well as to the time of rupture. The interval between diagnosis of prolapse of the umbilical cord and termination of birth was also in the focus of interest.-The authors concluded that the overall definition of "breech presentation" was quite inadequate and should be replaced, at least, by differentiation between real breech presentation and combined breech-footling presentations, in order to make allowance for the highly differentiated risks involved.-Therefore, a demand is made for strict differentiation of approach in key with presentation. Delivery should be terminated immediately in cases of prolapse of the umbilical cord in concomitance with real breech presentation or vertex presentation, whereas no direct time pressure existed in cases of combined breech-footling presentation.-The approach taken to all kinds of breech presentation, above all real breech presentation, should be identical with that taken to vertex presentation for adequately programmed delivery which has been a growing demand.-All conclusions proposed are discussed in great detail and substantiated as well as supported by comprehensive literature data.

Breech Presentation↗

[Risk of premature rupture of membranes and prognosis of premature delivery (author's transl)].

Premature rupture of the membranes was found to suppress rather than step up mortality, as was shown by examination of 919 newborns with birth weights of 2,500 g and less. The same conclusion was statistically secured for birth weights between 1,500 g and just below 2,000 g (p less than or equal to 0.05).-The above findings are likely to underscore results obtained by other authors who reported less occurrence of respiratory distress syndromes in premature newborns delivered after premature rupture of the membranes.-The frequency of premature ruptures tends to rise strongly along with declining birth weight, and similar correlations exist between perinatal mortality and birth weight. The authors, therefore, insist on the need for comparing only infants of one and the same birth weight (100 g-intervals), in order to forestall erroneous conclusions, otherwise inevitable.

Birth Weight↗