Inherited XX sex reversal in the cocker spaniel dog.

Nine XX true hermaphrodites and two XX males were discovered in a family of American cocker spaniels. The true hermaphrodites were partially-masculinized females with ovotestes; the XX males had malformed male external genitalia and cryptorchid aspermatogenic testes. Wolffian and Mullerian duct derivatives were present in both true hermaphrodites and XX males. All four sires of sex-reversed dogs were normal XY males; five of the dams were anatomically normal females and one was an XX true hermaphrodite. A second true hermaphrodite reproduced as a female, producing anatomically normal offspring. All matings that produced sex-reversed offspring were consanguineous. Matings of the parents of sex-reversed cocker spaniels to normal beagles with no family history of intersexuality produced only normal offspring. Examination of G-banded karyotypes of the affected animals, their parents, and siblings, revealed no structural anomalies of the chromosomes that were consistently associated with sex-reversal. In assays for serologically-detectable H-Y antigen, the group of XX true hermaphrodites and the group of XX males had mean levels of the antigen not significantly different from that in normal male controls. Female parents of sex-reversed dogs and some of their female siblings were typed H-Y antigen positive, but the mean level of the antigen in this group was less than that of normal male controls. It is proposed that XX sex reversal in cocker spaniels is due to a mutant gene which when homozygous in females, results in a level of H-Y antigen similar to that found in normal males and the gonads develop as ovotestes or testes. When the gene is heterozygous in females, the level of serologically-detectable H-Y antigen is lower than that found in normal males and the gonads develop as normal ovaries. The persistence of Mullerian structures in the presence of testicular tissue suggests that Mullerian inhibiting substance is deficient or ineffective in its action in this condition.

Chromosome studies of patients with Alzheimer disease.

Ten patients with either the familial or sporadic form of Alzheimer disease (AD) were studied cytogenetically to confirm reports of aneuploidy and "long acentric fragments" associated with the disease. Findings in leukocytes of patients were compared with those in eight unaffected relatives and seven persons of similar age. Observations from encoded slides involving 3,800 conventionally stained and 1,396 G-banded metaphases (one patient) showed no significant increase in aneuploidy. The frequency of cells with hypermodal counts, a reliable measure of aneuploidy, was 4.2% and 1.1%, respectively, in women and men with familial AD and 4.0% and 2.3%, respectively, in women and men with the sporadic form of the illness. Similar frequencies of hypermodal cells occurred in female (2.6%) and in male (2.0%) control subjects. In contrast to the lack of aneuploidy, a small but significant number of false "long acentric fragments" was found in cells of women with AD (P less than .05). These aberrations are thought to represent premature centromere division (PCD) in intact chromosomes, primarily supernumerary Xs. Often in multiple copies, PCD occurred in 2.8% of their cells and in 0.6% of cells from control women. PCD occurred in 3.6% of cells of women with the familial form and in 1.7% of cells of women with the sporadic type of dementia. Among unaffected relatives PCD increased with age. The rarity of PCD in G-banded metaphases from an affected female (3/1,396) suggests that metaphase spreading techniques also may affect observable frequency. Thus PCDs occur more frequently in, but are not unique to, AD and may represent an epiphenomenon of aging, a process also characterized by the occurrence of neurofibrillary tangles and senile plaques in the cerebral cortex.

Isolation and characterization of a neuroblastoma cell line from peripheral blood in a patient with disseminated disease.

Circulation in the blood stream of neuroblastoma cells was confirmed by establishment of a cell line from the peripheral blood of a child with disseminated disease. The morphologic, enzymatic, and chromosomal pattern of this cell line was similar to a cell line established from the primary tumor on a previous occasion. The peripheral blood smear did not demonstrate tumor cells but increased numbers of atypical monocytes; lymphoblasts were evident, which may have been unrecognized neuroblasts.

Abnormal chromosome 22 and recurrence of trisomy-22 syndrome.

Trisomy-22 was confirmed with both Q- and G-banding in two sibs. Growth and mental retardation plus various dysmorphic features of this syndrome are described and compared with previous reports. Cytogenetic studies reveal a morphologically atypical No. 22 in cells of the phenotypically normal mother (46,XX) and in both affected children. The variant G chromosome is identified as No. 22 by Q- and G-banding and is interpreted as a product of a pericentric inversion on the basis of general length, arm ratio (1.4), and anomalous satellite association frequency. Repeated nondisjunction for No. 22 is considered to have resulted from asynapsis caused by interference of an inversion loop configuration which, though short, comprised a major part of chromosome 22.

Reappraisal of karyological monitoring of diploid cell substrates.

The practical aspects of present requirements for karyological monitoring of diploid human fibroblasts used in vaccine production are critically re-examined. A brief review of known chromosomal instabilities and their correlations with neoplasia and with in vitro conversions of cell growth is presented and discussed in relation to karyological criteria in the selection of mammalian diploid cell substrates. It is proposed that extensive experience with the growth and karyological characteristics of human diploid fibroblast cell strains of embryonic origin may warrant the reduction or elimination of karyological monitoring of production lots. Additional requirements for characterization of cell strains for approval as substrates for vaccines are suggested which involve evaluations of chromosomal stability based upon (a) viral transformation rate and (b) aberration production rate in response to x-irradiation.

Establishment and characterization of human neuroblastoma cell lines.

Three new tissue culture cell lines, CHP-100, CHP-126, and CHP-134, have been established from explant cultures of human neuroblastoma. The cell lines have been characterized with respect to morphology, chromosomes constitution, growth, neural enzyme content, and their ability to grow in nude mice. The cells grow as dense masses comprised of fibroblast-or neuroblast-like cells with small processes. The cell lines differ in their neural enzyme acitivity. The chromosomal content of the 3 cell lines is near diploid, and all are capable of forming tumors in nude mice. The morphological findings indicate that the cells in culture resemble those found in the tumor, and the enzyme activities are consistent with those of nervous tissue. This the morphological, biochemical, and tumorigenic properties confirm that the 3 cell lines are neoplastic cells of neural origin.

The Giemsa banding pattern of the canine karyotype.

The canine metaphase karyotype consists of 78 chromosomes. All autosomes exhibit telocentric or acrocentric configurations gradually diminishing in size. These features make identification of homologous pairs by conventional analysis difficult. Chromosome preparations were derived from short-term cultures of peripheral blood lymphocytes obtained from clinically normal dogs representing at least four breeds. Most components of the canine karyotype can be distinguished readily. No significant G-banding pattern variations were detected in the individuals screened. An idiogrammatic interpretation of the banding pattern is presented. Apart from bands, other characteristic morphologic features were found which aid in identification. The G-banding pattern of the canine metacentric X is quite similar to that of the banded human X. The canine Y is a minute metacentric having two positive bands.