Human mid-trimester amniotic fluid cells were cultivated under conditions of decreased oxygen supply. Compared to control cultures the low-oxygen group showed improved growth which was quantitated by three independent assays (1) direct cell counts, (2) bromodeoxyuridine (BrdU)-Hoechst flow-cytometry, and (3) cloning efficiency. The growth promoting effects of lowered oxygen hold for all major morphologic categories of amniotic fluid cells.
Inadequate midfacial and forebrain development may result from constitutional chromosome aberrations, gene defects and, possibly, from as yet unidentified terato-genetic agents. The spectrum of clinical manifestations ranges from cyclopia with grossly incomplete organogenesis of the forebrain to apparently minor deviation from normal midface morphogenesis presenting as hypotelorism or absence of the philtrum. Such minor facial dysmorphias may, however, be likewise accompanied by severe anomaly in brain development and function. We report six cases of holoprosencephaly defects in children without demonstrable chromosomal anomalies. The presenting clinical symptoms in these cases were anomalies of cranio-facial shape, hypotelorism; nasal and ocular malformations, as well as median clefts. Some cases presented additional defects in extra craniofacial regions. Two infants who survived for several hours showed evidence of forebrain defects on CT-scans. Three of the cases suggest autosomal-recessive inheritance with 25% recurrence risk on the basis of proven or highly probable parental consanguinity. The remaining, presumably sporadic cases carry a low empirical recurrence risk. Three of the six cases received direct or indirect hormone treatments during early pregnancy.
Newer genetic investigations show that the complete or classical hydatidiform mole has in over 90% of the cases a diploid female set of chromosomes which is exclusively of paternal origin. The 23 X sperm genom is doubled and the nucleus of the ovocyte is degenerated. In contradistinction the nucleus of the ovocyte persists in partial moles. The normal ontogenesis is also disturbed by a preponderance of paternal genetic material. By melting of 2 instead of 1 paternal germ cell (Dispermia) the genom of partial moles is to 1/3 of maternal and to 2/3 of paternal origin. The triploid set of chromosomes shows usually 69xxy. Whereas the potential of malignancy of partial moles is low a choriocarcinoma results from 2 to 10% of the complete moles. Responsible maybe recessive hereditary mutations of growth controlling genes, which are present in complete moles in a homozygote form due to the doubling of a single paternal set of chromosomes. Total absence of the growth controlling loci of these genes maternally permits an unhibited expression of the growth controlling paternal genes.
Now that we know about the genetic production mechanisms of diseases of the trophoblast, interest is concentrated on the question which risk factors can produce a disposition in the patient - seen from a clinico-genetic angle - towards malignancy of a complete mole. Many years before the genetic interrelations became known, there had been discussions on blood relationship as a possible aetiological factor in the production of chorionic carcinoma. Since consanguinity in preceding generations can lead to a selection of certain genotypes, this question was reexamined on a limited patients material (10 patients with chorionic carcinoma and 11 with mole). The negative result of this study contradicts - similar to other recent publications on this subject - the hitherto frequently advanced hypothesis that homozygotism is responsible, for a recessive "onko" gen, for rendering a complete mole malignant. Recent investigations, for example, point to a close correlation between the presence of a Y chromosome in a complete mole, and malignancy.
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