Search PubMed⌕ Search

Biomedical subjects

D R Mattison

Publications and source records attributed to D R Mattison.

At least 73 records · Page 4Linked to original sources
PubMed1988

Magnetic resonance imaging: a noninvasive tool for fetal and placental physiology.

Nuclear magnetic resonance imaging (MRI), a technique that utilizes biochemical information reflected in nuclear magnetic moments, can be used to image the uterus, fetus, and placenta of the human and nonhuman primate. MRI studies during pregnancy in the human and nonhuman primate provide soft-tissue structural information of considerable detail. MRI also offers the opportunity for noninvasive pharmacokinetic and toxicokinetic studies during pregnancy. Paramagnetic ions (Cu, Ni, Gd, Fe, Mn) after spin-lattice (T1) and spin-spin (T2) relaxation times in reproductive tissues. Changes in T1 and T2 alter the MRI image, reflecting uptake of paramagnetic ions by the uterus, placenta, or fetus. MRI provides a noninvasive method of monitoring body burden of selected xenobiotics during gestation. The use of paramagnetic labels on endogenous substances may also allow noninvasive determination of physiological parameters such as intervillous blood flow, placental metabolism, and placental transport during gestation.

Animals↗
PubMed1988

Computer modeling of human fertility: the impact of reproductive heterogeneity on measures of fertility.

As a result of the paucity of biological markers for both reproductive events and exposure to reproductive toxicants, it is likely that individual members of populations will be misclassified with respect to reproductive performance and xenobiotic exposure. A four-parameter computerized model of fertility (frequency of intercourse, male fecundity, female fecundity, and spontaneous abortion) was developed to explore the effect of misclassification of populations on several measures of fertility. The measures of fertility explored include cumulative percent pregnant, time to pregnancy, cycle specific fertility, and fecundability ratio. The cumulative percent pregnant and time to pregnancy appeared to be insensitive to small changes in reproductive competence. The fecundability ratio decreased in proportion to the size of population exposed to a reproductive toxicant. The three reproductive parameters, time to pregnancy, cumulative percent pregnant, and fecundability, do not appear useful as measures of reproductive heterogeneity in populations. The reproductive heterogeneity of a population was best defined by the change in cycle-specific fertility rate over the period of observation. These simulations suggest that the change in the cycle-specific fertility rate should be evaluated and comparable in all population groups over the period of observation to assure reproductive homogeneity.

Abortion, Spontaneous↗
PubMed1988

Galactose inhibition of ovulation in mice.

Clinical evidence suggests an association between galactosemia and premature ovarian failure. In the present study, adult female mice were fed a diet consisting of 50% galactose for either 2, 4, or 6 weeks. At all times there was a decrease in the normal ovulatory response, as evidenced by a reduction in the number of corpora lutea when compared with controls. Additionally, the exposure of galactose-treated mice to a superovulatory regimen of pregnant mare's serum gonadotropin (PMSG) and human chorionic gonadotropin (hCG) failed to induce an increased ovulatory response. Morphologic alterations, such as the increase in interstitial tissue and the appearance of lipofuscin, coupled with the failure to respond to exogenous gonadotropins, suggest that the reduced ovulatory response may be occurring at the level of the ovary. This effect, however, is reversible with cessation of galactose treatment.

Animals↗
PubMed1987

Experimental and clinical studies on the reproductive toxicology of 2,3,7,8-tetrachlorodibenzo-p-dioxin.

The reproductive toxicology of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has been studied in animal models and in human populations. In animals, TCDD has a range of toxic effects on organs of the reproductive system in males and females, on hormone biochemistry, and on embryo-fetal development. These effects may involve in part an identified intracellular TCDD receptor and its association with the induction of microsomal cytochrome P-450-dependent monooxygenases in many organs. TCDD treatment increases activity of monooxygenase enzyme in liver and gonads of treated animals, but unlike other polycyclic aromatic hydrocarbons that are monooxygenase inducers, TCDD is not cytotoxic to any population of oocytes in the mature female mouse. Epidemiological studies of TCDD reproductive toxicity have been limited in design. There are some reports of adverse effects in the Seveso population and in children born to American veterans presumed to have been exposed to TCDD in Agent Orange during the Vietnam war. Occupational cohorts have not been found to show such paternally mediated effects of TCDD exposure.

Abnormalities, Drug-Induced↗
PubMed1987

Mechanisms of regulation of rat ovarian 7,12-dimethylbenz[a]anthracene hydroxylase.

The mechanisms of regulation of ovarian 7,12-dimethylbenz[a]anthracene (DMBA) hydroxylase were investigated with respect to hormonal requirements and effects of the antiestrogen tamoxifen and known inducers of cytochrome P-450. The DMBA hydroxylase is increased endogenously about 3-fold in the proestrus phase as compared to the metestrus/diestrus phases (M. Bengtsson and J. Rydstrom, Science, 219 (1983) 1437-1438). A similar effect was caused by the gonadotropins follicle-stimulating hormone (FSH) and luteinizing hormone (LH) whereas pregnant mare's serum gonadotropin (PMSG) brought about a 3-7-fold increase, suggesting that the estrus cycle-dependence of the DMBA hydroxylase was due directly or indirectly to gonadotropins. In contrast, differentiation of granulosa/theca cells to corpus luteum cells after ovulation, caused by administration of human chorionic gonadotropin (hCG), led to a marked decrease in activity. The activity was not specific for DMBA since substitution of this hydrocarbon for benzo[a]pyrene (BP) as substrate gave similar results. A possible role of estrogens in this context was investigated by the administration of tamoxifen simultaneous with gonadotropin treatment, which caused a partial inhibition of the hydroxylase activity. Both estradiol and 3-methyl-cholanthrene (MC) increased DMBA hydroxylase but the effects of these agents were not additive. In contrast, the effects of estradiol and MC were partially additive to that of gonadotropin. On the basis of these results, it is proposed that the rat ovary contains one or several aryl hydrocarbon hydroxylases located in the granulosa/theca cells which are regulated by estrogens, MC and beta-naphthoflavone (BNF) and that the role of gonadotropins is to proliferate granulosa/theca cells.

Animals↗
PubMed1987

Effect of oocyte number and rate of atresia on the age of menopause.

Menopause occurs when oocyte number falls below the threshold required for ovarian function. The age of menopause is decreased by some drugs, some occupational exposures, and cigarette smoke (both active and passive). Using data collected by Block (Acta Anat (Basel) 1954; 14:208), we have constructed four, two parameter models to explore the effect of oocyte number and rate of atresia on age at menopause. The models used are: linear [O(A) = OB + R * A]; natural log [O(A) = R * In (A)]; exponential [O(A) = OB * exp(R * A)], and power [O(A) = OB * Age(R)]. OB = oocyte number at birth, ATR = rate of atresia, and O(A) = number of oocytes at age A. The parameters for the four models are: (formula; see text) Each model has different behavior with respect to alterations in oocyte number and rate of atresia on age at menopause. Animal studies suggest that ovarian failure is only weakly dependent on oocyte number, consistent with the power and exponential models. These suggest that the decrease in age at menopause following xenobiotic exposures results from an increase in the rate of atresia.

Age Factors↗
PubMed1987

Magnetic resonance imaging of monkey placenta with manganese enhancement.

Magnetic resonance imaging of pregnant cynomolgus monkeys in the last trimester was done on a Picker instrument (Picker International, Inc., Northford, Connecticut) operating at 0.26 tesla. Both inversion-recovery and spin-echo proton images were obtained, demonstrating good detail of fetal and maternal anatomy. The placenta was particularly easy to identify, and its image was further enhanced by a bolus infusion of manganese chloride. Manganese is one of several paramagnetic ions that shortens proton relaxation times, and as a result alters signal intensity in magnetic resonance imaging. An infusion of 10 mumol/kg of manganese chloride was chosen on the basis of an in vitro experiment demonstrating shortening of the spin-lattice relaxation time at increasing concentrations of manganese. Additional studies showed rapid serum clearance of manganese after an intravenous dose with subsequent rapid uptake in the placenta. These results demonstrate that manganese is potentially suitable for studying placental blood flow with magnetic resonance imaging.

Animals↗
PubMed1987

Biological markers of male reproductive toxicology.

Reproduction is a complex, stepwise series of processes that begins with gametogenesis, continues through gamete interaction, implantation, embryonic development, growth, parturition, and postnatal adaptation, and is completed with the development and sexual maturation of the newly formed organism. These reproductive processes do not take place in a chemically pristine environment, but rather in an environment increasingly contaminated with the products and by-products of the chemical age in which we live. Some environmental pollutants are known to be carcinogenic, mutagenic, or toxic to the reproductive system, but most have not been adequately tested for reproductive toxicity. Just as reproduction is complex, biological mechanisms underlying toxicology are similarly complex and involve absorption, distribution, metabolism (toxification and/or detoxification), excretion, and repair. The synthesis of these sciences into the relatively nascent science of reproductive toxicology includes teratology, pharmacology, epidemiology, and occupational and environmental health. Female reproductive function (especially pregnancy outcome) has historically been the focus of attention, but there is increasing interest in the effects of chemical exposure on male reproductive function. Several reports have documented the physiology, biochemistry, and toxicology of male mammalian reproduction, and evaluated susceptibility of the male to the effects of exogenous chemicals.

Animals↗
PubMed1987

Kinetic assessment of manganese using magnetic resonance imaging in the dually perfused human placenta in vitro.

The transfer and distribution of paramagnetic manganese was investigated in the dually perfused human placenta in vitro (using 10, 20, 100 microM Mn with and without 54Mn) using magnetic resonance imaging (MRI) and conventional radiochemical techniques. The human placenta concentrated 54Mn rapidly during the first 15 min of perfusion and by 4 hr was four times greater than the concentrations of Mn in the maternal perfusate, while the concentration of Mn in the fetal perfusate was 25% of the maternal perfusate levels. Within placentae, 45% of the 54Mn was free in the 100,000g supernatant, with 45% in the 1,000g pellet. The magnetic field dependence of proton nuclear spin-lattice relaxation time (T1) in placental tissue supports this Mn binding. Mn primarily affected the MRI partial saturation rather than spin-echo images of the human placenta, which provided for the separation of perfusate contributions from those produced by Mn. The washout of the Mn from the placenta was slow compared with its uptake, as determined by MRI. Thus, Mn was concentrated by the human placenta, but transfer of Mn across the placenta was limited in either direction. These studies also illustrate the opportunity for studies of human placental function using magnetic resonance imaging as a noninvasive biomarker.

Female↗
PubMed1987

Pharmacokinetics and expert systems as aids for risk assessment in reproductive toxicology.

A minimal approach to risk assessment in reproductive toxicology involves four components: hazard identification, hazard characterization, exposure characterization, and risk characterization. In practice, risk assessment in reproductive toxicology has been reduced to arbitrary safety factors or mathematical models of the dose-response relationship. These approaches obscure biological differences across species rather than using this important and frequently accessible information. Two approaches that are formally capable of using biologically relevant information (pharmacokinetics and expert system shells) are explored as aids to risk assessment in reproductive toxicology.

Animals↗
PubMed1987

Effects of manganese (Mn++) and iron (Fe+++) on magnetic resonance imaging (MRI) characteristics of human placenta and amniotic fluid.

The contrast and intensity of a magnetic resonance image (MRI) is affected in part by the spin-lattice relaxation time (T1) and spin-spin relaxation time (T2). Certain paramagnetic metal ions can alter these parameters suggesting that they may be useful contrast agents in MRI. In this study, Mn++ and Fe+++ were examined for their effects on T1 and T2 in human placenta and amniotic fluid (AF) at concentrations between 0.002 and 2.0 mM. Both Mn++ and Fe+++ produced a dose-dependent decrease in placental and AF T1. The effects of Fe+++ were not pronounced, decreasing T1 only at the highest concentrations, and not to the same degree as Mn++. Placental T2 was also significantly decreased by Mn++, whereas Fe+++ had no effect. These differences may be due to molecular binding, uptake by the placenta, or the paramagnetic characteristics of the metals. The results suggest that Mn++ will alter human placental MRI for T1 and to a lesser extent T2-dependent imaging processes. Fe+++ should have little or no effect on human placental MRI, except at very high concentrations.

Amniotic Fluid↗
PubMed1986

Effect of manganese on human placental spin-lattice (T1) and spin-spin (T2) relaxation times.

Human placentas were obtained immediately following delivery and incubated with manganese chloride (MnCl2) in concentrations ranging from 0.002 to 2.0 mM. Proton density, T1 and T2 were measured at times ranging from 5-200 minutes. There was rapid uptake of manganese by the placenta producing a dose-dependent decrease in placental T1 and T2. The major effect of manganese uptake was shortening of T1 suggesting that the contrast between placenta and myometrium will be enhanced predominantly for T1-dependent imaging pulse sequences.

Chlorides↗
PubMed1985

Benzo(a)pyrene inhibits ovulation in C57BL/6N mice.

Successful female reproductive function requires follicle growth, ovulation, and formation of the corpus luteum. Treatment of C57BL/6N mice with a single intraperitoneal injection of benzo(a)pyrene in doses ranging from 1 to 500 mg/kg produced a dose- and time-dependent decrease in the number of corpora lutea. This effect on the number of corpora lutea is most pronounced at 1 week after treatment, with a threshold of about 1 mg/kg, and an ED50 of 1.6 mg/kg. By 2 weeks after treatment partial recovery of follicle growth and ovulation occurred, as indicated by an increase in the ED50 to 20 mg/kg. Complete recovery of normal corpora lutea number occurs in mice treated with less than 100 mg/kg by 3 weeks after treatment, with little change in the ED50 noted between 3 and 4 weeks post-treatment, 78 mg/kg at both times. Mice treated with 100 or 500 mg/kg did not recover normal corpora lutea number over the course of this experiment. These data indicate that acute exposure to benzo(a)pyrene, and perhaps other polycyclic aromatic hydrocarbons, may have a transient adverse effect on follicle growth, ovulation, or formation of corpora lutea. A consequence of this effect, transient infertility, has been observed previously when exploring the effect of polycyclic aromatic hydrocarbons on murine reproduction.

Animals↗
PubMed1985

Murine oocyte destruction following intraovarian treatment with 3-methylcholanthrene or 7,12-dimethylbenz(a)anthracene: protection by alpha-naphthoflavone.

Bilateral or unilateral intraovarian injection with the polycyclic aromatic hydrocarbons 3-methylcholanthrene (3-MC), or 7,12-dimethylbenz(a)anthracene (DMBA) destroys oocytes in C57BL/6N and DBA/2N mice. The threshold for small oocyte destruction following bilateral intraovarian treatment with 3-MC was between 0.1 and 1 microgram/ovary in both DBA/2N amd C57BL/6N mice. After intraovarian treatment with DMBA, a more potent ovotoxin, the thresholds for small oocyte destruction were between 0.01 and 0.1 microgram/ovary. Calculated ED50's for small oocyte destruction following bilateral intraovarian treatment with 3-MC were C57BL/6N, 0.33 micrograms/ovary; DBA/2N, 1.02 micrograms/ovary--for DMBA the ED50's were C57BL/6N, 0.11 micrograms/ovary; DBA/2N, 0.03 micrograms/ovary. Unilateral intraovarian treatment also destroyed oocytes in the treated ovary. Treatment with intraperitoneal alpha-naphthoflavone (ANF), a competitive inhibitor of polycyclic aromatic hydrocarbon metabolism by microsomal monooxygenases, inhibited oocyte destruction. Intraovarian treatment with ANF decreased oocyte destruction produced by intraovarian DMBA. These data suggest that both 3-MC and DMBA are indirect acting ovotoxins requiring metabolic activation before oocyte destruction occurs. In addition, these data also suggest that the ovary contains the enzymes necessary to biotransform xenobiotics like 3-MC and DMBA to ovotoxic metabolites. Metabolic activation of xenobiotics to reactive products within the ovary may represent a special threat to the integrity of oocyte DNA.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1984

Monoclonal antibodies to the major protein of the murine zona pellucida: effects on fertilization and early development.

The growing murine oocyte is surrounded by an extracellular zona pellucida consisting of three sulfated glycoproteins, ZP-1, ZP-2, and ZP-3. The smallest of these, ZP-3, has been reported to be the species-specific sperm receptor. Monoclonal antibodies have been recently characterized to three different antigenic determinants, two found exclusively on ZP-2, and one found on both ZP-2 and ZP-3. The in vivo effect of these antibodies on the three known functions of the zona pellucida were examined. The most dramatic effect was the prevention of fertilization. After administration, the monoclonal antibodies were located in the ovary on the zona pellucida of growing oocytes. Eggs ovulated subsequently were coated with the monoclonal antibodies and failed to develop into 2-cell embryos after mating. Eighty days later, the monoclonal antibodies could no longer be detected on the zona of ovarian oocytes, and this loss coincided with the resumption of fertility. These findings provide molecular evidence for the hypothesis that the immunological block to sperm-egg binding need not involve antibody specific for the sperm receptor, and that antibodies to the zona pellucida block sperm access by steric hinderance. Other known functions of the zona were unaffected. The antibodies were unable to induce the biochemical changes in the zona associated with the postfertilization block to polyspermy and had no detectable effect on preimplantation development.

Animals↗