Fetal cerebrohepatorenal (Zellweger) syndrome: dysmorphic, radiologic, biochemical, and pathologic findings in four affected fetuses.

Four fetuses with positive family histories for cerebrohepatorenal (Zellweger) syndrome (CHRS) underwent diagnostic amniocentesis or chorionic villus biopsy. Cultured amniocytes or fibroblasts from all of the fetuses displayed abnormal fatty acid ratios, and the parents elected therapeutic abortions. Dysmorphic features in one fetus consisted of micrognathia, proximal implantation of toes, and bilateral talipes equinovarus. Radiologic examination of the fetus confirmed the dysmorphic features and revealed foci of mineralization in the patellae. Biochemical analysis of three of the fetuses demonstrated markedly increased levels of very-long-chain fatty acids, both saturated and monounsaturated, in liver, kidney, adrenal, and brain. Pathologic findings consisted of premature mineralization of patellae; renal cystic tubular dilations; striated cells in adrenal fetal zone and testicular interstitium; dysplastic alterations of inferior olivary nuclei, dentate nuclei, and cerebral cortex; equivocal increases in portal fibrous tissue; and abnormal cytosomes in fetal zone adrenocortical cells, testicular and renal interstitial cells, and brain macrophages. Iron deposition, probably physiologic, was observed only in liver tissue. Distributions of immunoreactive catalase were identical in the fetuses with CHRS and age-matched control subjects. These findings document the accuracy of the prenatal diagnostic test and provide insights into the morphogenesis and pathogenesis of CHRS.

Sister chromatid exchange in cancer.

Sister chromatid exchange (SCE) techniques have been shown to have great potential for use in the in vitro screening of suspected mutagens and carcinogens. Application of these techniques to bone marrow cells and/or lymphocytes from patients with various hematologic malignancies has demonstrated significant abnormalities in SCE frequencies in some of these diseases, as well as showing drug treatment effects. Interpretation of abnormal SCE findings in cancer patients is currently hindered by the lack of a clear understanding of the basic molecular and biochemical mechanisms involved in SCE formation. The potential practical use of SCE techniques in the diagnosis and treatment of cancer can not adequately be appreciated until this basic understanding is achieved.

Chromosomal instability in ataxia telangiectasia.

We have examined various aspects of lymphocyte chromosomal instability in three families comprised of five individuals affected with ataxiatelangiectasia (AT), their obligate heterozygous parents, and their unaffected sibs. We found that neither baseline sister chromatid exchanges (SCEs) nor mitomycin-C-induced increments in SCEs showed any significant differences among family members or between AT heterozygotes or homozygotes. Chromosome breakage in first-division metaphases was found to be moderately elevated in three of the five AT homozygotes (range 1-12%); breakage in the six AT obligate heterozygotes was within normal limits (0-4%). Analysis of Giemsa-banded metaphases indicated the presence of a clone bearing a paracentric inversion of chromosome #14 in addition to other chromosome #14 abnormalities in one AT homozygote. The same inversion was also found in this individual's affected sister and his obligate heterozygous father. A discussion regarding the relationship of the specificity of breakage and reunion of bands q12 and q23 on chromosome #14 and the high incidence of malignancy in AT is included.

Vasopressin: action on WRK-1 rat mammary tumor cells.

WRK-1, a cell line in long-term culture derived from a 7, 12-dimethylbenz[a]anthracene-induced rat mammary tumor, responds to physiologic concentrations of vasopressin with increased precursor incorporation into phospholipids and with increased protein accumulation. Because vasopressin has been reported to be a potent mitogen for Hela cells and 3T3 cells, a study was conducted to determine whether it could act as a mitogen for WRK-1 cells. Under no conditions was a clear-cut mitogen response to vasopressin demonstrated.

Gm and Km(Inv) frequencies in two Roumanian populations.

Serum samples from 170 unrelated individuals from the Suceava District of Roumania and from 199 unrelated individuals from Bucharest, Roumania were tested fro Gm(1,2,3,5,6,13,14,17,21) and Km(1)[Inv(1)]. Selected samples were also tested for Gm(15) and Gm(16). The frequencies of the three common Caucasoid haplotypes, Gm3,5,13,14, Gm1,17,21, and Gm1,2,17,21 in these two populations were found to be similar to those in neighboring Slavic states and Hungary. Racial admixture was evidenced by the presence of the Gm1,13,15,16,17 and Gm1,3,5,13,14 haplotypes, which are primarily Mongoloid, and the Gm1,5,13,14,17 haplotype which is primarily Negroid. Comparisons of these data with those from earlier studies of populations from Central Europe indicate that the frequency of the Gm3,5,13,14 haplotype within this region is high and essentially uniform. Published data for several blood group systems also indicate essentially uniform distributions of frequencies in this region. It is suggested that this region may be the center of a cline that radiates from it.