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Biomedical subjects

E C Miller

Publications and source records attributed to E C Miller.

At least 73 records · Page 4Linked to original sources
PubMed1982

[Amino acid imbalances in blood of pregnant women with diabetes and in blood of their newborns--limit values for screening (author's transl)].

Blood-borne free amino acids of 100 mothers were tested immediately after birth. Fifty of the probands had diabetes, while the other 50 were metabolically intact. Amino acid imbalance was recorded by means of multidimensional variance analysis from the diabetics and found to have been largely associated with glutamic acid threonine, alanine, glycine-serine, and glutamine.--A formula, derived from the aforementioned relevant amino acid concentrations, is given in this paper together with a nomogram (which might be used instead of the formula) for determination of diabetes-caused alterations in the amino acid spectrum

Amino Acids↗
PubMed1982

[Amino acid imbalance in the blood of pregnant diabetic women and their newborn infants--limit values for screening. II. Neonatal amino acid imbalance].

Free amino acids were studied in the blood of 50 newborns each of women with intact metabolism and of diabetic mothers. The tests were conducted immediately after delivery and on the fifth day of age. Amino acid imbalance reflected, after birth, in changed concentrations of glutamic acid-threonine, alanine and glycin-serine was recordable from newborns of the diabetic mothers. However, nothing but significant changes in concentrations of glutamic acid-threonine and alanine was recordable on the fifth day of age. --An account is given of the formulae and nomograms (applicable instead of these formulae) for postpartum amino acid concentrations and for concentrations on the fifth day of age, being established by discriminant analysis. These can be used to identify alterations inflicted upon amino acid metabolism by diabetes mellitus.

Amino Acids↗
PubMed1981

Searches for ultimate chemical carcinogens and their reactions with cellular macromolecules.

Studies on a variety of chemical carcinogens have demonstrated that their ultimate reactive and carcinogenic forms are strong electrophiles. Some carcinogens, such as alkylating agents, are in their ultimate forms as administered, but most require metabolism to these active derivatives. The ultimate carcinogens react, usually non-enzymatically, with nucleophilic constituents in vivo. Of particular interest in regard to their possible importance in carcinogenesis have been the covalent interactions of these electrophilic reactants with cellular informational macromolecules, the DNAs, RNAs, and proteins. Current data are consistent with the idea that the initiation step of chemical carcinogenesis is a mutagenic event and is caused by alteration of DNA by the ultimate carcinogens. The nature of the carcinogen metabolite(s) involved in the promotion phase has not been determined, but there appears to be no requirement that they be electrophilic. The development of the concept of ultimate chemical carcinogens as strong electrophilic reactants is reviewed, especially with respect to the studies carried in the authors' laboratory.

2-Acetylaminofluorene↗
PubMed1981

The side-chain epoxidation and hydroxylation of the hepatocarcinogens safrole and estragole and some related compounds by rat and mouse liver microsomes.

Safrole, estragole, and their 2',3'-oxides were hydroxylated by hepatic microsomes from rats and mice at the 1'-carbon; trans-anethole was hydroxylated at the 3'-carbon; and safrole, estragole, and their 1'-hydroxy derivatives were epoxidized at the 2',3'-double bond. The 2',3'-epoxidation of eugenol was just detectable. The formation of these metabolites was dependent on an NADPH-generating system and on cytochrome P-450. In the absence of 3,3,3-trichloropropylene oxide little or no safrole-, estragole-, or eugenol-2',3'-oxide was recovered when these oxides were added to the incubations; recoveries of 50-70% were obtained in its presence. The recoveries of the 2',3'-oxides of 1'-hydroxy-safrole and of 1'-hydroxyestragole were 50-80% in the absence of trichloropropylene oxide and nearly quantitative in its presence. All incubations for analysis of epoxidation rates contained trichloropropylene oxide. The rates of metabolite formation ranged from about 0.4 nmol of eugenol-2',3'-oxide/mg protein/h by female rat liver microsomes to about 270 nmol of trans-3'-hydroxyanethole/mg protein/h for male rat liver microsomes. The rates of epoxidation and hydroxylation were greater for the estragole derivatives than for the safrole derivatives. The rates of epoxidation of safrole and estragole were greater than for their 1'-hydroxy derivatives.

Allylbenzene Derivatives↗
PubMed1981

Mechanisms of chemical carcinogenesis.

Of the known carcinogenic agents (viruses, ultraviolet and ionizing radiations, and chemicals), chemicals appear to be of major importance in the induction of human cancers. The known chemical carcinogens include a wide range of structures. Their common feature is that their ultimate forms are electrophilic reactants; in most cases, these reactants arise through metabolism in vivo. Carcinogenesis by chemicals is a multistage process. The first stage, initiation, occurs rapidly and appears to be irreversible. The available data indicate that initiation generally results from one or more mutations of cellular DNA. Covalent reactions of electrophilic derivatives of carcinogens with DNA are the major cause of these mutations. The second stage, promotion, occurs over a longer period of time. Promotion is a complex process, for which the early stages are largely reversible. The critical events appear to be epigenetic. Complete carcinogens have both initiating and promoting activities, but the ratios of these two activities for various chemicals may differ greatly. This knowledge of the mechanisms of carcinogens by chemicals provides a useful basis for approaches to the prevention of human cancer.

Animals↗
PubMed1981

The in vivo formation and repair of DNA adducts from 1'-hydroxysafrole.

1'-Hydroxysafrole is a proximate carcinogenic metabolite of the naturally occurring hepatocarcinogen safrole. Comparison by high-performance liquid chromatography of the nucleoside adducts obtained from hepatic DNA of adult female mice treated with [2',3'-3H]1'-hydroxysafrole with those formed by reaction of deoxyribonucleosides with electrophilic derivatives of 1'-hydroxysafrole indicated that the four in vivo adducts studied were derived from an ester of 1'-hydroxysafrole. Three of the four adducts comigrated with products of the reaction of 1'-acetoxysafrole with deoxyguanosine, whereas the fourth adduct comigrated with the major reaction product of the ester with deoxyadenosine. Analysis of the three deoxyguanosine adducts indicated that all three involve substitution on the 2-amino group of guanine. A sample of ther major adduct prepared from deoxyguanylic acid has been characterized from its NMR spectrum as N2-(trans-isosafrol-3'-yl)-deoxyguanosine, and the deoxyadenosine adduct has been similarly characterized as N6-(trans-isosafrol-3'-yl)-deoxyadenosine. Repair replication was measured in cultured human T98G cells exposed to 1'-acetoxysafrole using the combined 5-bromodeoxyuridine density label and radioisotopic label method. At a concentration of 1 mM 1'-acetoxysafrole, the amount of repair synthesis approached maximum values only about 15% of those obtained after saturating doses of ultraviolet light. Repair patch size distribution was found to be similar in cells treated with ultraviolet light or 1'-acetoxysafrole as determined by the density of repair-labeled DNA relative to that of parental DNA.

Animals↗
PubMed1981

[Insulin requirements of the diabetic woman during pregnancy, labor, delivery and the puerperium (author's transl)].

The author demonstrates - contrary to all existing opinions - that without doubt insulin demand increases very early and relative continually; it stagnates only in the last weeks of pregnancy. Therefore gravid women have a resource of insulin - sufficient to guarantee (for sake of fetus) a constant level of blood-glucose. The author argues, that it may be taken for granted, that above all other hormones human placental lactogen (HPL) is responsible for regulation of carbohydrate metabolism during pregnancy. One of the most important consequences of these results is the necessity, to control the renal insulin demand of pregnant women at brief intervals (not longer than 14 days). That is the most certain way to protect fetus from injury (fetopathia!), caused by anomal high concentration of maternal blood-glucose. Moreover: alteration of insulin demand signal the condition of placenta, thus enabling the physician to act in due time.

Diabetes Mellitus↗
PubMed1981

Comparative carcinogenicities and reactivities of N-myristoyloxy-N-acetyl-2-aminofluorene and its 7-iodo derivative.

Earlier studies showed that N-acetyl-2-aminofluorene (AAF) is much more carcinogenic than N-acetyl-2-amino-7-iodofluorene (AAIF). Subsequently it was found that substitution of C-8 of guanine bases in DNA with AAF residues resulted in displacement of the guanine bases outside the DNA helix. This did not occur after similar substitution with AAIF residues. As one approach to assessing the possible importance of this gross conformational difference to the carcinogenicity of AAF, the carcinogenic activities of two electrophilic esters, N-myristoyloxy-AAF and its 7-iodo derivative, were compared by s.c. injection into male Fischer rats. On injection of a total of 64 mumol, each ester induced a high incidence of sarcomas, and the latent periods were similar. N-Myristoyloxy-AAIF was solvolyzed in aqueous media at about one-half the rate of N-myristoyloxy-AAF, and it was less than 10% as reactive with native DNA as N-myristoyloxy-AAF. N-Myristoyloxy-AAF and N-myristoyloxy-AAIF were each less reactive than the corresponding acetoxy derivatives. These data suggest that the low carcinogenicity of AAIF as compared to that of AAF may not be associated with the conformations of their adducts in the DNA. This difference in carcinogenicity may be related to differences in the rates of metabolic activation and inactivation of these two amides.

2-Acetylaminofluorene↗
PubMed1981

Mutagenicity, tumorigenicity, and electrophilic reactivity of the stereoisomeric platinum(II) complexes of 1,2-diaminocyclohexane.

Without external activation, cis- and trans-dichlorodiammineplatinum(II) (DDP) and the cis, trans(-), and trans(+) forms of dichloro-1,2-diaminocyclohexaneplatinum(II) (DDCP) and sulfato-1,2-diaminocyclohexaneplatinum(II) (SHP) showed a 400-fold range of mutagenicity for Salmonella typhimurium TA100 and TA98; they were 2 to 10 times more mutagenic for strain TA100 than for strain TA98. With strain TA100, trans-DDP was less than 0.5% as mutagenic as the cis isomer, which produced 180 revertants/nmol. For the diaminocyclohexane complexes, mutagenic activity was strongly dependent on the stereoisomer of the diaminocyclohexane in the complex. Thus, with strain TA100, the trans(+) forms of DDCP and SHP produced 220 and 66 revertants/nmol, respectively, while the cis and trans(-) isomers induced only 10 and 5% as many revertants as the trans(+) forms. The SHP complexes were the most reactive toward DNA and produced a greater reduction in the transforming activity of Bacillus subtilis DNA after 3-hr reaction times than did the DDP or DDCP complexes. With 20-hr reaction times, all of the platinum complexes showed similar extents of reaction with DNA and caused approximately equal losses of transforming activity. The stereoisomeric form of the diaminocyclohexane ligand of the DDCP or SHP complexes did not affect either the reactivity of the complex with DNA or its ability to reduce the transforming activity of DNA. Significant increases in the number of lung adenomas in A/J mice were induced by multiple i.p. injections of cis-DDP and each of the DDCP and SHP complexes (total doses, 21 to 108 mumol/kg body weight). Similar treatments with cis-DDP caused a significant increase in the number of skin papillomas in female CD-1 mice given promoting treatments with croton oil; the DDCP and SHP complexes had little or no activity in this system. At these levels, trans-DDP was not active for the induction of either lung adenomas or skin tumors. With the systems used for this study, the mutagenicities and tumorigenicities of the platinum(II) complexes did not correlate with their reported antitumor activities. Further studies appear warranted to determine whether there may be effective antitumor platinum(II) complexes that are not strongly mutagenic or carcinogenic.

Animals↗
PubMed1981

Quantitative analysis of the time-dependent development of glucose-6-phosphatase-deficient foci in the livers of mice treated neonatally with diethylnitrosamine.

The development of glucose-6-phosphatase (G-6-Pase-)-deficient hyperbasophilic foci was analyzed at 4-week intervals in the livers of CD-1 and C57BL/6J x C3H/HeJ F1 (hereafter called B6C3F1) mice given a single i.p. injection of diethylnitrosamine (DEN) (0.1, 0.2, or 0.4 mumol/g body weight) within 24 hr after birth. Transections of G-6-Pase-deficient foci of hepatocytes were readily discernible in liver sections of DEN-treated mice of either sex at 8 weeks of age. The size and number of these foci per liver increased with time. The occurrence of G-6-Pase-deficient focus transections with diameters as large as 1 mm coincided with the gross appearance of 1-mm gray-white nodules in the livers of male B6C3F1 mice at 16 weeks of age and in females at 32 weeks of age. Transections of all grossly visible hepatic nodules from male and female mice were G-6-Pase deficient and hyperbasophilic; the great majority were diagnosed as mouse hepatomas type A. After a single neonatal dose of DEN, the number and rate of growth of the G-6-Pase-deficient foci and the incidence and rate of appearance of gross hepatomas were greater in the liver of male than in those of female mice. In contrast, the average numbers of G-6-Pase-deficient foci in the livers of male and androgenized female B6C3F1 mice at 36 weeks of age were approximately equal and about twice that observed for the livers of DEN-treated female controls. Quantitation of carcinogen-induced histochemically detectable foci and hepatomas as a function of time provides a useful tool for the analysis of initiation and promotion in the mouse liver.

Age Factors↗
PubMed1981

[Frequency of breech presentation during pregnancy and on full term (author's transl)].

The causes underlying the relationship between breech presentation and premature birth were studied, with reference to the premature birth discussion which has assumed sizeable dimensions in the obstetric community. -- An evaluation of 785 ultrasonographic findings from pregnant women has shown breech presentation to be just as frequent as vertex presentation up to the 24th week of pregnancy. The former, consequently, should be considered as physiological. The frequency of breech presentation was found to go down continuously only beyond the 24th week and to drop below five per cent, after the 35th week of pregnancy to reach eventually the figure usually recorded at birth. These observations were found to be in good agreement with what has been reported by other authors. -- The authors of this paper were struck by surprise, when they found that the breech presentation figure, in the context of 997 premature births, was, with high significance, below the level usually recordable from unimplanted pregnancy. -- The above findings are discussed in great detail. Preliminary suggestions are made regarding possible interpretations. Yet, further target-oriented studies are required.

Breech Presentation↗
PubMed1981

N2 atom of guanine and N6 atom of adenine residues as sites for covalent binding of metabolically activated 1'-hydroxysafrole to mouse liver DNA in vivo.

Administration of 1'-[2'-3'-3H]hydroxysafrole to adult female mice resulted in the formation of DNA-, ribosomal RNA-, and protein-bound adducts in the liver that reached maximum levels within 24 hr. The levels of all three macromolecule-bound adducts decreased rapidly between 1 and 3 days after injection, at which time the amounts of the DNA-bound adducts essentially plateaued at approximately 15% of the maximum level. The amounts of the protein and ribosomal RNA adducts were very low by 20 days. Comparison by high-performance liquid chromatography of the deoxyribonucleoside adducts obtained from the hepatic DNA with those formed by reaction of deoxyguanosine and deoxyadenosine with 1'-acetoxysafrole, 1'-hydroxysafrole-2',3'-oxide, and 1'-oxosafrole indicated that the four in vivo adducts studied were derived from an ester of 1'-hydroxysafrole. Three of the four in vivo adducts comigrated with adducts formed by reaction of 1'-acetoxysafrole with deoxyguanosine; the fourth adduct comigrated with the major product of the reaction of this ester with deoxyadenosine. Adduct formation in vivo at low levels by the other two electrophilic metabolites was not excluded. The three adducts obtained by reaction of 1'-acetoxysafrole with deoxyguanosine appeared to be substituted on the 2-amino group of the guanine residue on the basis of their partitions between aqueous buffer solutions and 1-butanol:ethyl ether as a function of pH and their retention of 3H from [8-3H]deoxyguanosine. The corresponding three adducts derived from the hepatic DNA of mice given 1'-[2',3'-3H]hydroxysafrole had pH partition patterns not significantly different from the three adducts formed in vitro. Adduct II was further characterized from its nuclear magnetic resonance spectrum as N2-(trans-isosafrol-3'-yl)deoxyguanosine. Adduct IV, derived from the reaction of 1'-acetoxysafrole with deoxyadenosine 5'-phosphate, was characterized in the same manner as N6-(trans-isosafrol-3'-yl)deoxyadenosine.

Animals↗
PubMed1981

[Effects of mother's age and parity status on body size of newborns (author's transl)].

Body length of newborns was found to be influenced clearly by both parity and mother's age, as was borne out by an analysis of more than 21.000 births. Body lengths of newborns were found to increase along with rising order number of births and growing maternal age, yet, only up to a certain age limit beyond which newborn length tended to be stagnant or to decline, depending on parity status. An attempt is made to elucidate possible causes by correlating the author's own results with findings reported elsewhere in literature.

Adult↗
PubMed1981

[Obstetric manipulations including amnioscopy, amniotomy, and vaginal examination and duration of labour -- impact on maternal susceptibility to infection (author's transl)].

A detailed analysis was made of 139 deliveries, which had been systematically supervised, following amnioscopy and pelvimetry, in comparison to 104 deliveries, following spontaneous onset of labour and timely rupture of the amnion. Both variants were compared for the relative risk of infection to the mothers involved. --While infection morbidity was, surprisingly, unaffected by the interval between rupture and parturition, it was found to depend strongly on the duration of labour with the amniotic sac intact. --Morbidity, also, went up clearly along with the number of previous amnioscopies and of surgical deliveries, in particular caesarean section. --Discoloration of amniotic fluid, obviously, did not stimulate germ growth nor was any detrimental effect recordable from vaginal examination. --Early artificial rupture is considered good prophylaxies not only against infection but also against asphyxia.

Female↗
PubMed1981

[Prognostication of foetal weight by means of ultrasonic foetometry. Study into accuracy of various formulae and analysis of error sources (author's transl)].

The author conducted a large-scale study into all accessible formulae for foetal weight assessment on the basis of ultrasonic measurement. Included were the author's own recently devised formulae. They were all studied for their accuracy, with reference being made to 100 unselected data groupings.--Another analysis was made for the purpose of finding out the extent to which the number of data used by different examiners could change differences between estimated results derived from formulae. Reference in great detail is made also to the effects of measurement errors and selection of data upon formula results.--Proper choice of measurement level was found to be important. Abdominal parameters proved to be superior to thoracic parameters. Estimated results, generally, improved along with the number of foetal measuring points, provided they were really relevant and weightful.--Discussed is the relative value which should be ascribed to all factors with impact on the accuracy of weight prognosis. Proper choice of an adequate mathematical model or adjustment of such choice to foetal data is considered to be essential, because it has to be made by optimum consideration of all factors.--All the above formulae were verified, but accuracies claimed earlier by original authors were reproducible only in some rare cases. The demand, therefore, is made that whenever new formulae are introduced the best of all available techniques of assessment should be used to compare their results, with reference to be made to the same, unselected patients. This is considered to be the best way for an objective assessment of their advantages.--An account is given of those practicable formulae which can be recommended, as a result of the comparison, and for which easy-to-use nomograms are available.

Anthropometry↗