A methodology designed to eliminate mitotic inhibitor action and involving use of pretested fetal calf serum and careful pH and temperature control has been described by which cells from normal human and animal tissue can be maintained in active growth for long periods in vitro without development of aneuploidy. By means of this procedure, it is possible reliably to establish cell cultures from minute skin biopsies which can be taken from any individual. Clones of mammalian cells with chromosomal markers have been isolated by this means from x-irradiated non-irradiated cell cultures. Application of these techniques to chromosome delineation in large numbers of human subjects; determination of chromosomal sex in patients; spontaneuos and induced genetic changes in somatic mammalian cells in vivo and in vitro; comparison of metabolic differences between normal and cancerous cells and other problems have been indicated.

Sixty-seven adolescents participated in this protocol, including 42 with sex chromosome abnormalities and 25 controls. Results from a battery of neuropsychological tests indicated karyotype specific patterns of neuropsychological impairment: (1) 47,XXY boys had unimpaired intelligence but reduced abilities in verbal fluency and reading; (2) 47,XXX girls experienced reduced general intelligence accompanied by impaired scores on individual tests of attention, concept formation, spatial thinking, verbal fluency, and academic skills, while retention of memorized information was a relative strength; (3) among the 45,X girls average intelligence level was also reduced along with scores on tests of attention, concept formation, verbal fluency, spatial thinking, and academic skills, and an atypical pattern of hand dominance was identified; (4) test scores in the group of mosaic females did not differ from those of controls. Test scores and patterns of personal adaptation were quite variable in all groups; while eight nonmosaic propositi required intensive special education assistance in their public schooling, eight others have attended college.

factor activities in both the fetal lamb and in the mother ewe. The changes were not consistent with classical disseminated intravascular coagulation. An additional stress such as hypotension is probably required to induce intravascular coagulation in the fetus. The exact mechanism responsible for the observed changes remains unclear. The changes are not related to mere exposure of fetal blood to a lowered pH. The observation that the mother ewes also experience a reduction in factor V and factor IX activity in the absence of lactic acidosis suggests the liberation of a mediator from the fetus capable of crossing the placenta. These observations support the original findings of Bishop et al. (3) ondary sexual changes, basal serum hormone concentrations and acute responses to stimulation with gonadotropinreleasing hormone and human chorionic gonadotropin were normal. The timing of the onset of clinical puberty was normal. Early pubertal boys showed initial testicular growth and normal serum testosterone levels, while serum follicle-stimulating hormone and estradiol concentrations were significantly elevated. By midpuberty, the Klinefelter subjects were uniformly hypergonadotropic and their testicular growth had ceased. Serum testosterone concentrations after age 15 remained in the low-normal adult range. Serum estradiol levels remained high, irrespective of the presence or absence of gynecomastia. Exaggerated responses to gonadotropin-releasing hormone are seen in pubertal subjects with elevated basal gonadotropin values.