PubMed Health⌕ Search

Biomedical subjects

P G Kratzer

Publications and source records attributed to P G Kratzer.

13 recordsLinked to original sources
PubMed1992

Cytogenetic evidence for enhanced selective miscarriage of trisomy 21 pregnancies with advancing maternal age.

The effect of advancing maternal age on the risk of death of fetuses with certain chromosome abnormalities has been tested by comparing their frequency at the time of chorionic villus sampling (CVS) with that at amniocentesis. The frequency of chromosome abnormalities among women whose sole risk factor for a chromosome abnormality was advanced maternal age (> or = 35 years old) was determined in a pooled group of 15,147 CVS cases, of whom > 1/3 were from the initial 7,500 CVS cases at the University of California, San Francisco, and compared with a pooled group of 74,851 amniocentesis cases collected from the literature. The frequency of trisomy 21 not only increased with advancing maternal age as expected, but the slope of the increase was about 25% greater in the CVS group than in the amniocentesis group (P = 0.08 for the difference in slopes by a logistic statistical model and P = 0.04 by a normit model). Similar patterns were seen for trisomies 18 and 13, but the P values for the differences in slopes were much higher. These results suggest that the miscarriage rate of trisomy 21 during the gestational interval studied is selectively greater with advancing maternal age. The basis for the enhanced selective loss of trisomy 21 with maternal age may be a reduced ability of the ageing "maternal compartment" to compensate for abnormal conceptuses.

Abortion, Spontaneous↗
PubMed1991

Trisomic pregnancies have normal human chorionic gonadotropin bioactivity.

Sera from women carrying either chromosomally normal or aneuploid fetuses in the first half of pregnancy were assayed for human chorionic gonadotropin (hCG) bioactivity in order to determine whether differences might provide the basis for a useful antenatal screen for aneuploidy. A mouse uterine weight assay was used to assess hCG bioactivity in sera from 35 patients undergoing chorionic villus sampling (12 normal pregnancies and 23 trisomic pregnancies) and in sera from 18 patients undergoing elective second-trimester abortion (12 presumed normal pregnancies, 3 trisomic pregnancies, and 3 pregnancies with neural tube defects). The hCG bioactivity to immunoactivity (B:I) ratio of normal pregnancies progressively decreased from 7.7 +/- 1.3 at 4-5 menstrual weeks, to 4.7 +/- 0.4 at 9-12 menstrual weeks, to 3.3 +/- 0.5 at 16-20 menstrual weeks. There were no significant differences in the B:I ratios between normal and aneuploid pregnancies in either the first-trimester (4.7 +/- 0.4 versus 5.2 +/- 0.3) or the second-trimester samples (3.3 +/- 0.5 versus 2.6 +/- 0.3), despite significantly greater hCG concentrations in the trisomic pregnancies. We conclude that while aneuploid pregnancies display dysfunctional regulation of hCG expression, the bioactivity of their hCG is normal and does not appear to form the basis for a useful screen for aneuploidy.

Aneuploidy↗
PubMed1991

First-trimester aneuploidy screening using serum human chorionic gonadotropin (hCG), free ahCG, and progesterone.

Immunochemical serum assays for human chorionic gonadotropin (hCG), the free ahCG subunit, and progesterone (P) were considered separately and in combination for their ability to screen for chromosomally abnormal pregnancies in the first trimester. Maternal serum was collected from 141 women undergoing chorionic villus sampling at 9-12 menstrual weeks. Trisomy 21 pregnancies had significantly higher hCG levels, while trisomy 18 and 13 pregnancies had markedly lower hCG and progesterone levels than those of chromosomally normal pregnancies. However, the discrimination of normal from aneuploid pregnancies was poor with either hCG alone, progesterone alone, or free ahCG alone. Much improved discrimination was obtained by combining hCG, free ahCG, and P into an aneuploidy index [(P/hCG)(free ahCG/hCG)]. This index distinguished 9 out of 17 (53 per cent) of the trisomy 21 pregnancies, while only misidentifying 5 out of 112 (4.5 per cent) of the normal pregnancies. The aneuploidy index thus appears promising as a first-trimester biochemical screen for aneuploid pregnancies.

Aneuploidy↗
PubMed1990

Corpus luteum function in early pregnancies is primarily determined by the rate of change of human chorionic gonadotropin levels.

Regulation of human corpus luteum activity was studied with radioimmunoassays and bioassays of sera drawn serially from women suspected of having ectopic pregnancies. Progesterone values exhibited considerable overlap in pregnancies that were subsequently classified as normal intrauterine (n = 21), ectopic (n = 35), or spontaneous abortion (n = 14). The rate of change of human chorionic gonadotropin concentration was significantly correlated with progesterone levels in ectopic (r = 0.64) and all pregnancies (r = 0.70). There was no correlation (r = -0.18) between the rate of change of human chorionic gonadotropin and the bioactivity produced per volume of serum. Ectopic pregnancies and normal intrauterine pregnancies did not differ in their ratio of in vivo bioactivity to immunoactivity. From these data we conclude that corpus luteum activity is primarily regulated by the rate of change of human chorionic gonadotropin concentration, without the involvement of other serum factors. We also conclude that reduced corpus luteum function in ectopic pregnancies is not a result of biochemical modification of the human chorionic gonadotropin molecule. Finally, we discourage the use of single progesterone values in screening for ectopic pregnancies because of the considerable overlap in progesterone values among these and normal intrauterine pregnancies.

Abortion, Spontaneous↗
PubMed1983

Differences in the DNA of the inactive X chromosomes of fetal and extraembryonic tissues of mice.

We have examined the role of DNA modification in X chromosome inactivation of fetal tissues of the mouse using DNA-mediated gene transfer for the gene hypoxanthine phosphoribosyltransferase (HPRT). Two types of tissues have been examined with respect to randomness of inactivation in 14-day mouse conceptuses: 1) fetal tissue, which undergoes random inactivation of either the maternal or paternal X; and 2) yolk sac endoderm tissue, an extraembryonic membrane, which normally undergoes nonrandom inactivation of the paternal X. Exploiting an electrophoretic variant of HPRT as a means to mark the active and inactive HPRT alleles we provide evidence that: 1) inactive X DNA of the fetus at 14 days behaves like that of both adult tissue and cell lines in that the inactive X DNA is not efficient in gene transfer; and 2) in contrast, inactive X DNA from yolk sac endoderm is functional in gene transfer. Thus, despite the similarity in single active X chromosome expression in yolk sac endoderm and somatic tissues, there appears to be a difference at the level of DNA modification between these two tissues.

Animals↗
PubMed1983

Electrophoretic variation for X chromosome-linked hypoxanthine phosphoribosyl transferase (HPRT) in wild-derived mice.

An electrophoretic variation for hypoxanthine phosphoribosyltransferase, HPRT, has been identified in samples of Mus spretus, a field mouse from southern Europe and in M. m. castaneus, a house mouse from southeast Asia. These mice will interbreed with laboratory mice to produce viable, fertile F1 progeny. The variation for HPRT segregates as an X chromosome gene in F1 and backcross progeny. Linkage analysis involving the markers Pgk-1 and Ags indicated a gene order of centromere--Hprt--Pgk-1--Ags in crosses involving both stocks of wild mice.

Animals↗
PubMed1983

Expression of maternally and embryonically derived hypoxanthine phosphoribosyl transferase (HPRT) activity in mouse eggs and early embryos.

X-chromosome activity in early mouse development has been studied by a gene dosage method that involves measuring the activity level of the X-linked enzyme hypoxanthine phosphoribosyl transferase (HPRT) in single eggs and embryos from XO females and from females heterozygous for In(X)1H, a paracentric inversion of the X chromosome. The HPRT activity in oocytes increased threefold over a 24-hr period beginning after ovulation. Afterward, the activity plateaued in unfertilized eggs but continued to increase for at least 66 hr in presumed OY embryos. Both before and after ovulation, the level of activity in unfertilized eggs from In(X)/X females was twice that from XO females, and the distributions of activity in eggs for both sets of females remained unimodal. Beginning with the two-cell stage, distributions of activity for embryos from In(X)/X females were trimodal, which is evidence for embryonic activity. It is proposed that activation of a maternal mRNA or proenzyme is responsible for the HPRT activity increase in oocytes and early embryos and is supplemented by dosage-dependent activity of the embryonic Hprt gene as early as the two-cell stage.

Animals↗
PubMed1982

Evidence for DNA modification in the maintenance of X-chromosome inactivation of adult mouse tissues.

The role of DNA modification in the maintenance of mammalian X-chromosome inactivation was investigated by using the technique of DNA transformation in mammalian cells. The ability of inactive X-chromosome DNA from adult mouse tissues to act in transformation for the X-linked hypoxanthine phosphoribosyltransferase gene (Hprt) could be ascertained by utilizing a recently discovered electrophoretic variant form of the hypoxanthine phosphoribosyltransferase enzyme and a previously available X:autosome translocation. Our findings indicate that inactive X-chromosome DNA from several tissues of adult female mice is strikingly inefficient, in comparison to active X-chromosome DNA, in eliciting genetic transformation for hypoxanthine phosphoribosyltransferase. These results provide in vivo evidence that is consistent with DNA modification playing an important role in the maintenance of X-chromosome inactivation.

Animals↗
PubMed1981

X chromosome reactivation in oocytes of Mus caroli.

Mature mammalian oocytes have both of their X chromosomes active, while somatic cells from the same individual have one of their X chromosomes in an inactive state. We asked whether the X chromosomes of the germ cells never undergo inactivation in their ontogeny or whether inactivation of an X chromosome does occur but is followed by a subsequent reactivation event. Our approach has used an electrophoretic polymorphism for the X-linked enzyme glucose-6-phosphate dehydrogenase (G6PD) in the mouse species Mus caroli. G6PD is dimeric, and a heterodimer is produced in cells from heterozygous females if and only if both X chromosomes are active. Ovaries from heterozygous fetuses at different gestational ages were dissected and either studied cytologically or pressed between microscopy slides to obtain germ cell-rich and germ cell-poor preparations. No heterodimer band was detected on the 10th day of development in germ cell-rich preparations. On subsequent days, an increasingly intense heterodimer band was detected, which, by the 13th day, was approximately twice as intense as the corresponding homodimer bands. Consideration of (i) the G6PD activity per germ cell and per somatic cell and (ii) the percentage of germ cells in the germ cell-rich preparations indicated that a heterodimer band should have been visible on the 10th day had both X chromosomes been active. Cytological examinations showed that the earliest germ cells enter meiotic prophase on the eleventh day. These results demonstrate that oogonia have a single active X chromosome and that the inactive X chromosome is reactivated at or, more likely, shortly before entry into meiotic prophase.

Alleles↗