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D K Manchester

Publications and source records attributed to D K Manchester.

44 records · Page 3Linked to original sources
PubMed1982

Resolution and reconstitution of human placental monooxygenase activity responsive to maternal cigarette smoking.

Human placental cytochrome P-450 monooxygenase activity toward 7-ethoxyresorufin increases in response to maternal cigarette smoking and is specifically inhibited in vitro by 7,8-benzoflavone. Using a mixture of ionic and nonionic detergents we have solubilized placental cytochrome P-450 CO binding and cytochrome C reductase activities and separated them by anion exchange chromatography. Fractions containing cytochrome P-450 from placentas from smokers will catalyze 7,8-benzoflavone-inhibitable activity in reconstituted systems. SDS polyacryl-amide gel electrophoresis reveals proteins (molecular weight 70,000-40,000) in cytochrome P-450-containing fractions, derived from women who smoke, which are not detected in material from nonsmokers. These findings support the contention that placental response to maternal smoking involves induction of cytochrome P-450.

Cytochrome P-450 Enzyme System↗
PubMed1981

Sensitivity of human placental monooxygenase activity to maternal smoking.

The in vitro oxidation of 7-ethoxyresorufin was studied in placental microsomes from 47 full-term pregnancies. Placental activities were compared in four groups formed on the basis of maternal smoking history as follows: nonsmokers (n = 12), passive smokers (n = 16), 1 to 20 cigarettes/day (n = 13), and 20+ cigarettes/day (n = 5). Passive smoking was defined as living with someone who smoke cigarettes. Umbilical cord plasma thiocyanate concentrations were measured to confirm histories and were higher when mothers smoked (80 +/- 10 micro M, 1 to 20 cigarettes/day, 116 +/- 8 micro M, 20+ cigarettes/day) than when mothers did not smoke (34 +/- 3 micro M, nonsmokers; 35 +/- 3 micro M, passive smokers). 7-Ethoxyresorufin O-deethylase activity was increased 10- to 30-fold in placentas from smokers. Activity toward 7-ethoxyresorufin in placentas from smokers was markedly inhibited in vitro by addition of 7,8-benzoflavone. Among nonsmokers, percent inhibition of O-deethylase activity by 7,8-benzoflavone was greater (P less than 0.05) in placentas from women passively exposed to cigarette smoke. Human placental monooxygenase activity is sensitive to both active and passive cigarette smoke exposure.

Benzoflavones↗
PubMed1977

The effect of birth on the maturation of hepatic cytochrome(s) P-450 mono-oxygenase and tyrosine aminotransferase activities in the guinea pig.

Mixed coat guinea pigs delivered by Cesarian section 5 days before term were compared to spontaneously delivered full-term animals with respect to the postnatal maturation of hepatic mono-oxygenase activity in vitro toward aniline and p-chloro-N-methylaniline. Tyrosine aminotransferase acitivity was studied in the same preparations as a positive control for birth-related phenomena. Mono-oxygenase activities toward both sustrates increased significantly in both premature and full-term animals during the first 3 postnatal days and approached adult values 72 h after birth. The maturation of tyrosine aminotransferase activity occured in a qualitatively similar fashion. The mechanism through which birth initiates the maturation of drug oxidative capacity is unresolved; the gestational age at which competence to respond to the event of birth is acquired, remains undefined.

Aniline Compounds↗
PubMedDate not supplied

Binding of 2,3,7,8-tetrachlorodibenzo-p-dioxin to AH receptor in placentas from normal versus abnormal pregnancy outcomes.

Binding of [3H]2,3,7,8-tetrachlorodibenzo-p-dioxin to AH receptor was characterized in cytosol from human placentas in which the pregnancy outcome was normal compared with pregnancies in which there was some adverse outcome (premature birth; intrauterine growth retardation; structural abnormality). No significant difference was detected between normal and adverse outcomes in the concentration of AH receptor sites (Bmax) nor in the affinity with which [3H]TCDD bound to the receptor (Kd). Aryl hydrocarbon hydroxylase activity, a CYP1A1 enzyme regulated by the AH receptor, was elevated in placental microsomes from smokers; this elevation was associated with intrauterine growth retardation.

Aryl Hydrocarbon Hydroxylases↗
PubMedDate not supplied

Derivative fluorescence spectral analysis of polycyclic aromatic hydrocarbon-DNA adducts in human placenta.

Metabolic activation in humans of chemical carcinogens found in the environment results in the formation of carcinogen-DNA adducts in vivo. Some polycyclic aromatic hydrocarbon-DNA adducts in human DNA can be hydrolyzed under mildly acidic conditions to yield tetrahydrotetrol derivatives which may then be detected by synchronous fluorescence spectroscopy. In an analysis of human placental DNA, second derivative spectroscopy alone was unable to resolve the synchronous fluorescent signature for r-7,t-8,t-9,c-10-tetrahydroxy-7,8,9,10-tetrahydrobenzo[alpha]pyrene from a crude extract, because a complex array of other fluorescent materials was also present. Purification of the sample by a combination of chromatographic procedures including immunoaffinity chromatography and HPLC has now been shown to yield r-7,t-8,t-9,c-10-tetrahydroxy-7,8,9,10-tetrahydrobenzo[alpha]pyrene residues from human DNA that are spectroscopically pure at the second derivative level. Immunoaffinity columns were prepared with rabbit antiserum raised against DNA that had been modified with (+/-)-r-7,t-8-dihydroxy-t-9,10-epoxy-7,8,9,10-tetrahydrobenzo[alpha]pyre ne. This antiserum has now been shown to recognize DNA samples that have been modified with six different polycyclic aromatic hydrocarbon diol epoxides and is probably only specific for a broad spectrum of polycyclic aromatic hydrocarbon-DNA adducts. Adducts were eluted from the immunoaffinity columns, hydrolyzed with acid, and extracted into isoamyl alcohol, before being subjected to high-performance liquid chromatography. These experiments reveal important limitations of second derivative fluorescence spectroscopy as a tool in the analysis of complex environmental mixtures. Furthermore, they extensively define the ability of anti-benzo[alpha]pyrenediol epoxide-DNA antibodies to recognize different types of polycyclic aromatic hydrocarbon-DNA adducts.

Biotransformation↗
PubMedDate not supplied

X-linked myotubular myopathy: a case report of prenatal and perinatal aspects.

Nine families have been reported in which male newborns presented with X-linked myotubular (centronuclear) myopathy. Little is known about the biochemical basis of this disorder or about its natural history in utero. We report a family in which an infant with myotubular myopathy presented in utero with polyhydramnios, poor fetal movement, and fetal cardiac arrhythmias. Shortly after birth the infant died from severe respiratory insufficiency. Gas chromatography-mass spectrophotometry for serum organic acids showed a large octanoic acid peak, but total acyl-CoA dehydrogenase activities in liver were normal. The maternal family history was significant for two perinatal male deaths. Postmortem examination revealed generalized muscle wasting, cardiac enlargement, cryptorchidism, and flexion contractures. Examination of muscle showed numerous fibers that had enlarged, centrally located nuclei and perinuclear clear zones. The muscle fibers were hypotrophic and predominantly of type I. Biopsy specimens of the muscles of the mother and maternal aunt had increased numbers of centrally located nuclei. Neurologic examination was normal. The case demonstrates the typical clinical course, pathology, and family history of severe X-linked myotubular myopathy. In addition, it confirms the reported detection of fetal cardiac arrhythmias and documents what may be an abnormality in fatty acid oxidation.

Family↗