Adenosine triphosphate: protection against radiation-indued chromosome loss in Drosophila.

Injection of 5 milligrams of adenosine triphosphate per milliliter into adult Drosophila melanogaster X(e2) yB/sc(8) y(+) 4 to 8 hours old either immediately before or after administration of 2000 roentgens of x-rays protected those cells in spermatogenesis which were in or near meiosis from the loss of the ring X or the y(+) portion of Y chromosome. The loss of the chromosomes was determined by appearance of exceptional XO males in the offspring.

The centralized prenatal genetics screening program of New York City III: The first 7,000 cases.

The Prenatal Diagnosis Laboratory of New York City (PDL) is a regional program for the prevention of genetic diseases. The administrative aspects of the establishment of the laboratory were described in papers I [Hsu, 1981] and II [Hsu and Benn, 1981] in this series. We now report our experience of the first 7,000 referrals to the laboratory. The laboratory achieved a success rate of 99.5% in obtaining a diagnosis. The frequency with which a repeat amniocentesis was required was 1.9%, usually attributable to inadequate initial amniotic fluid volume or condition. Cases were completed in an average time of 20.82 days. A total of 149 (2.13%) cytogenetic abnormalities were detected. There were 59 nonmosaic autosomal trisomies and 29 sex chromosome abnormalities. The incidence of unbalanced structural abnormalities (0.186%) was much higher than that reported in surveys of newborn infants largely because of the prenatal detection of cases with supernumerary chromosomes. The incidence of balanced structural abnormalities was also considerably higher than that found in surveys of the newborn population, in part because of the detection of subtle familial pericentric inversions of common chromosome regions (inv(Y)(p11q11), inv(2) (p11q13), and inv(1)(p11q13)). The incidence of cases with multiple independent chromosome abnormalities was no higher than expected by chance. A high incidence of mosaicism, pseudomosaicism, and maternal cell contamination was found. Screening for neural tube defects accounted for the detection of a further 16 abnormalities. Nearly all women with severely abnormal fetuses (trisomy 13, 18, 21) elected to terminate their pregnancy whereas only 62% of patients with a prenatally diagnosed sex chromosome abnormality elected to terminate their pregnancies. Full details of follow-up and confirmatory studies for unusual diagnoses are reported. Utilization of prenatal diagnosis in the New York City area has increased sharply since PDL became operational. The laboratory's success illustrates the role of a prenatal diagnosis laboratory that provides a service independent of the patient's financial status. The experience further shows the high degree of acceptance of prenatal diagnosis by individuals at high risk for a child with a genetic disorder.

Screening of karyotype and semen quality in an artificial insemination program: acceptance and rejection criteria.

Semen quality and karyotype were screened in all men offering to be donors for an artificial insemination (AID) program. The criteria for accepting or rejecting semen have now been set with respect to this sample of the population. There was no evidence of differences between the pregnancy rates of the accepted donors. One of 172 potential donors with a clear medical history had a chromosomal abnormality, 4 had pericentric inversions of chromosome 9, and 14 had other heterochromatic variants. Of the recipients of AID, 5 of 196 women had chromosomal abnormalities, and 12 had heterochromatic variants.

Cryopreservation of ICR mouse oocytes: improved post-thawed preimplantation development after vitrification using Taxol, a cytoskeleton stabilizer.

OBJECTIVE: To establish an effective cryopreservation method. DESIGN: In vitro model study. SETTING: Infertility Medical Center, Pochon CHA University. ANIMAL(S): Four-week-old ICR mice superovulated with pregnant mare serum gonadotropin (PMSG) and human chorionic gonadotropin. INTERVENTION(S): Vitrified-thawed oocytes were fertilized and subsequently cultured in vitro. MAIN OUTCOME MEASURE(S): Post-thawed development, chromosome/spindle normalities, and blastocyst quality. RESULT(S): More cumulus-enclosed oocytes were fertilized and developed to the 8-cell stage after vitrification and thawing than denuded oocytes. However, cryopreserved oocytes of both types had lower spindle and chromosome normalities than fresh oocytes, which resulted in reduced developmental competence after thawing. The addition of 1 microM of Taxol, a cytoskeleton stabilizer, to vitrification solution greatly promoted the blastocyst formation of vitrified-thawed oocytes, compared with no addition (24.0% vs. 58.6%). No difference in blastocyst quality, which was evaluated by blastomere and inner cell mass cell numbers and inner cell mass cell per trophoblast ratio, was found between fresh oocytes and oocytes vitrified with Taxol. CONCLUSION(S): A vitrification solution consisting of 5.5 M ethylene glycol, 1.0 M sucrose, 10% fetal bovine serum, and 1 microM Taxol greatly improved post-thawed development of vitrified oocytes.

Frequency of births with potentially avoidable serious chromosomal anomalies in EEC countries, 1979-1982.

Child bearing at an early age and prenatal cytogenetic diagnosis in pregnant women of advanced age, combined with selective abortion, make it possible to avoid the birth of many children with serious chromosomal anomalies. To see how many of such births were still avoidable in Europe, data from 16 regional EUROCAT registers of congenital anomalies in nine EEC countries were analysed. In the period 1979-1982 about 30% of children with unbalanced anomalies of autosomes were born (live- and still-births) to mothers over 35 years of age. This amounts to an estimated 1300 cases yearly in the entire population of the nine countries. The approach shows the possible use of registry data for monitoring effects of avoidance strategies.

Can preference scores for discrete states be used to derive preference scores for an entire path of events? An application to prenatal diagnosis.

The authors conducted a study exploring whether preferences for sequences of events can be approximated by preferences for component discrete states. Visual-analog-scale (VAS) and standard-gamble (SG) scores for a subset of the possible sequences of events (path states) and component temporary and chronic outcomes (discrete states) that can follow prenatal diagnostic decisions were elicited from 121 pregnant women facing a choice between chorionic villus sampling and amniocentesis. For individuals, preference scores for path states could not be predicted easily from discrete-state scores. Mean path-state VAS scores, however, were predicted reasonably accurately by multiple regression models (R2 = 0.85 and 0.82 for two different anchoring schemes), with most measured scores lying within the 95% confidence intervals of the derived scores. It is concluded that, for individual patient decision making, preferences for path states should be elicited. When mean preference values for a population are sought, however, it may be reasonable to derive regression weights from a subset of respondents and then to apply those weights to preferences for discrete states elicited from a larger group.

Inhibition of benzo[a]pyrene- and cyclophoshamide-induced mutagenicity by Cinnamomum cassia.

Cinnamomum cassia is used as a flavoring spice with some established medicinal properties. In this study, we evaluated the antimutagenic effect of C. cassia against two mutagens, viz. benzo[a]pyrene (B[a]P) and cyclophosphamide (CP). The antimutagenic properties of C. cassia were examined by the Ames test. In vivo chromosomal aberration (CA) and micronuclei tests were also employed to assess the antimutagenic effect of C. cassia in mice after pretreatment with the extract orally for seven consecutive days. To elucidate the mechanism by which C. cassia exerts its antimutagenic effect, certain key enzymes involved in bioactivation and detoxification processes were also investigated. Changes in liver cytochrome P450 (Cyt P450), glutathione content (GSH), glutathione S-transferase (GST), glutathione reductase (GR), and glutathione peroxidase (GPX) were evaluated in pretreated animals. It was observed in the Ames test, bone marrow chromosomal aberration assay, and micronucleus test that C. cassia exerted significant antimutagenic effects against B[a]P and CP in animals treated with the plant extract. C. cassia pretreatment decreased Cyt P450 content but increased GSH content and the activity of glutathione-dependent antioxidant enzymes, viz. GST, GR, and GPX. The present findings demonstrate that the antimutagenic potential of C. cassia could be attributed to its modulatory effect on the xenobiotic bioactivation and detoxification processes.

Factors that contribute to biomarker responses in humans including a study in individuals taking Vitamin C supplementation.

It is possible in many situations to identify humans exposed to potentially toxic materials in the workplace and in the environment. As in most human studies, there tends to be a high degree of interindividual variability in response to chemical insults. Some non-exposed control individuals exhibit as high a level of damage as some exposed individuals and some of these have levels of damage as low as many of the controls. Thus, it is only the mean values of the groups that can substantiate an exposure-related problem; the data on an individual basis are still of limited use. While human lymphocytes remain the most popular cell type for monitoring purposes, sperm, buccal, nasal, epithelial and placental cells are also used. However, for interpretation of responses, the issue of confounding factors must be addressed. There are endogenous confounding factors, such as age, gender, and genetic make-up and exogenous ones, including lifestyle habits (smoking, drinking, etc.) There are biomarkers of exposure, effect/response and susceptibility and the last may be influenced by the genotype and polymorphism genes existing in a population. From our own studies, confounding effects on cytogenetic damage and ras oncoproteins will be considered in relation to workers exposed to vinyl chloride and petroleum emissions and to volunteers taking Vitamin C supplementation. Smoking history, exposure and duration of employment affected the worker studies. For petroleum emissions, so did gender and season of exposure. For the non-smoking volunteer Vitamin C supplementation study, cholesterol levels, plasma Vitamin C levels, lipid peroxidation products and DNA damage in the Comet assay were also measured. Gender affected differences in Vitamin C levels, antioxidant capacity and the number of chromosome aberrations induced by bleomycin challenge in vitro. The results were the same for both high and low cholesterol subjects. The relationship between biomarkers and the various factors which affect them is complex. Sometimes the variables are not completely independent of each other.

Modulation of ochratoxin-produced genotoxicity in mice by vitamin C.

Ochratoxin A (OA), when administered orally daily for 45 days to albino Swiss mice, Mus musculus, at a level equivalent to the human dietary concentration of 1 microgram/kg body weight/day, increased the production of abnormalities in both mitotic and meiotic chromosomes as well as in the gross morphology of the sperm head. The sperm count per unit volume of caput epididymal suspension also decreased. Vitamin C at a concentration equivalent to the human therapeutic dose (10 mg/kg body weight/day), when administered orally concurrently with OA, significantly minimized the incidence of these abnormalities. The protective effect of vitamin C was most marked in mitotic chromosomes followed by that in meiotic chromosomes and sperm head morphology; the improvement in sperm count was least marked. The possible mechanism of this effect is discussed.

ACOG educational bulletin. Maternal serum screening. Number 228, September 1996 (replaces no. 154, April 1991). Committee on Educational Bulletins of the American College of Obstetricians and Gynecologists.

Maternal serum screening offers women the ability to increase the detection of open fetal defects, Down syndrome, and trisomy 18. After being informed of the risks and advantages of serum screening, a patient may elect to be screened. Counseling must emphasize that serum screening for these disorders is voluntary, and patients must be aware that further evaluation, if their results are classified as positive, may include amniocentesis. Physicians should have access to genetic services and reliable laboratories to assist them in the management of maternal serum screening and genetic procedures. Special attention must be given to the older gravida to help her make an appropriate personal decision regarding screening and genetic testing. Patients receiving positive results from a definitive test (karyotype or, possibly, ultrasonography) should have access to adequate counseling, including the availability of support groups and pediatric surgeons.

Testing for fetal abnormality in routine antenatal care.

The detection of fetal abnormality is a major component of routine antenatal care. A variety of techniques are now in use, although these are constantly being modified in the pursuit of more accurate and earlier detection. In this paper we draw attention to the distinction between screening and diagnostic tests, and describe the techniques which have been most commonly used in the UK: serum-screening for neural tube defects; screening for Down's syndrome; ultrasound scanning; amniocentesis and chorionic villus sampling.

Control of genetic defects.

Recombinant DNA techniques offer the possibility of diagnosing genetic defects directly by analysing DNA itself. This is especially interesting for detecting carriers of recessive defects. In comparison with phenotypic screening with progeny testing or biochemical tests, DNA screening is independent of the time of gene expression and is not influenced by non-genetic effects. If the mutation causing the defect is known, alterations of DNA sequences can be identified directly as restriction fragment length polymorphisms (RFLPs) or with the use of allele specific oligonucleotides (ASO). DNA amplification with the polymerase chain reaction makes screening tests faster and more accurate. For most defects, the genetic basis is not known. Pedigree analysis with linked polymorphic DNA markers can be used to establish defect diagnosis. Linkage analysis can locate the chromosomal region of the gene responsible for the disease. Identification of the gene and the mutation in the defect allele finally will lead to direct DNA diagnosis. A dense linkage map with highly polymorphic genetic markers covering the entire genome will in future improve understanding of polygenic diseases. Increasing knowledge of the molecular genetics of human defects will promote DNA diagnosis in other species.

Triphalangeal thumb and split foot in the same family.

The authors report a family with triphalangeal thumb with nail hypoplasia: one of them has also split feet. They believe that the existence of such families must make very circumspect with regard to genetic counseling for a minor problem such as triphalangeal thumb.

The cardio-facio-cutaneous (CFC) syndrome: autosomal dominant inheritance in a large family.

A large, three generation-family with firm evidence of autosomal dominant transmission of the cardio-faciocutaneous (CFC) syndrome is reported. This observation questions once more the validity of separating the CFC syndrome from the Noonan syndrome as two distinct entities.

Fetal hydrocephalus. Clinical significance of associated anomalies and genetic counseling: a pathological approach.

We report on a consecutive series of 94 cases of fetal hydrocephalus. Pathological and neuropathological findings have been thoroughly analysed in order to define more precisely the clinical significance of associated anomalies and their implications in genetic counseling. In 90.5% of cases, hydrocephalus was associated with other central nervous system (84%) or extra neural (56%) anomalies. True aqueductal stenosis occurred only twice in our series. In only 9 fetuses, hydrocephalus was an isolated finding, secondary to haemorrhage or infection. Since fetal hydrocephalus is an etiologically heterogeneous disorder, its recurrence varies greatly. Without a final diagnosis, based on well documented pathological data and cytogenetic studies, accurate genetic counseling and prenatal diagnosis in subsequent pregnancies would be impossible.

Cerebral midline developmental anomalies: spectrum and associated features.

Cerebral midline anomalies are defects of anatomical relationships between the two hemispheres. They include holoprosencephalies, septal and commissural agenesis. Agenesis of the olfactory tract (arhinencephalies) are often included in the spectrum of holoprosencephalies and the facial phenotype is thought to be affected and characteristic in the midline development abnormalities. This work concerns a review of the literature and personal experience in two units of Fetopathology in Paris. This study confirms the relationships between various cerebral malformations and their frequent association. However, arhinencephaly and moreover agenesis of corpus callosum should be considered as heterogeneous entities, often totally distinct and independent from the malformative process of the holoprosencephaly. In addition, if major facial anomalies such as cyclopia are almost pathognomonic for holoprosencephaly, minor malformations such as lateral facial clefts of cleft palates result from a great variety of malformative processes.

Protective role of ascorbic acid and vitamin B-complex against pesticide-induced clastogeny in bone marrow cells of mice.

Concurrent administration for one week of vitamins B-Complex (0.3 ml of 1% Polybion) or ascorbic acid (0.25 ml of 1% Redoxon, to 8-week old albino swiss mice, Mus musculus along with organophosphorous pesticide Malathion or carbamate pesticide Rogor (both 1 microliters/kg b.wt.) could significantly decrease the chromosome-clastogeny rate induced by the pesticides alone in the metaphase chromosomes of bonemarrow cells. The vitamins were not clastogenic, whereas the Malathion proved to be clastogenic four-times and Rogor six-times more than the control rate. The vitamins seem to reduce the incidence of fragmentation and subsequent rearrangements induced by the pesticides. On the basis of the available literature, it is presumed that the vitamins might be preventing the formation of mutagenic lipid conjugates of biometabolised forms of the pesticides.

Quality of life in Turner syndrome is related to chromosomal constitution: implications for genetic counselling and management.

Issues of self-appraisal, friendships and academic attainments are uniquely salient for all adolescents. For girls with Turner syndrome, social problems and learning difficulties often become more serious at this time, yet may be unacknowledged by those responsible for paediatric care because their focus is on growth and sexual maturation. Data on the social and educational adjustment of 110 45,X (monosomic) females aged between 6 and 25 years is presented. Detailed information on the patients' precise karyotype was used to demonstrate systematic differences in adjustment between those whose single X chromosome was maternally derived and those in whom it was paternal. Implications for educational support and parental guidance are discussed.

Rapid karyotyping in the second and third trimesters for fetuses at risk of chromosomal abnormalities at Chulalongkorn Hospital.

Transabdominal fetal blood sampling under ultrasonic guidance was performed in 20 fetuses at 18 to 34 weeks gestation. Pure fetal blood was obtained in all cases; 11 from the umbilical veins at the placental cord insertion, 7 from the fetal intrahepatic veins and 2 from the fetal hearts. Rapid karyotype was obtained within 7 days by fetal lymphocyte culture. Chromosomal abnormality was detected in 5 (25.0%) fetuses. Abnormal karyotype was found in 4 of 8 fetuses with structural malformations detected by antenatal ultrasound and in 1 of 5 fetuses of elderly mothers at advanced gestational ages. This suggested that in fetuses at risk of chromosomal abnormality, rapid karyotype should be obtained and fetal blood sampling is justified in the second or third trimester.

[Pregnancy following oocyte donation]. / Zwangerschap na eiceldonatie.

Five women, aged 31, 26, 31, 34, and 28 years, became pregnant after oocyte donation and in-vitro fertilization. One was a carrier of Leber's optical atrophy, three had had an early menopause (in two because of chromosomal abnormalities), and one had had bilateral ovarian extirpation because of a cystadenoma and endometriosis. Three developed (pre-)eclampsia during pregnancy and one had a serious fluxus post partum. One twin died in utero, the other children were healthy. In the Netherlands in-vitro fertilization (with or without egg-donation) takes place up to the age of about 40. Regarding the high incidence of obstetrical complications in women under 40, raising the age limit could lead to even more pregnancy problems. Candidates for oocyte donation should be informed about these risks, furthermore they should not deliver at home.