Complex de novo rearrangement involving four chromosomes and ten break points with interstitial deletions and duplication.

We describe an unusual de novo case of two interstitial deletions (5q22----5q31; 9q13----9p22) and one duplication (9q22----9p34) resulting from a 10-breakpoint, complex chromosome rearrangement of chromosomes 1, 5, 8, and 9 in a profoundly retarded woman.

Tetrasomy of the short arm of chromosome 9: prenatal diagnosis and further delineation of the phenotype.

A fetus with multiple malformations was identified by prenatal ultrasound investigation. Cordocentesis and fetal lymphocyte chromosome analysis demonstrated a model number of 47 chromosomes. The extra chromosome material was identified as an isochromosome of the entire short arm of chromosome 9 with no involvement of the heterochromatic region of the long arm [47,XY, + i(9p)]. This represents the first report of prenatal diagnosis of tetrasomy 9p. Further delineation of the phenotype is discussed.

Effects of LSD on human chromosomes.

A number of positive and negative studies have been reported with regard to the damaging effects of LSD on human chromosomes. The present report describes a comparative study of cytogenetic analyses of 200 metaphases of lymphocytes from each of 6 subjects (3 males, 3 females) at varying concentrations of LSD, along with a positive control with mitomycin C and a negative control with sterile water. Results of a small pilot study on the effects of LSD on growth, macromolecular synthesis, mutation, and recombination in bacteria, lambda phage and mammalian cells are also included. The data failed to show any significant differences between chromosome aberrations and LSD. Significant changes in somatic cells and in chromosomes occurred only at high doses of LSD.

Alteration of human breast tumor cell membrane functions by chromosome-mediated gene transfer.

BOT-2 cells (human breast tumor origin) have an impaired ability to utilize exogenous thymidine. Previous studies revealed this deficiency to be the permeation event rather than phosphorylation, since the cells have active thymidine kinase. Chromosome-mediated gene transfer was used to transfer genetic information in the form of metaphase chromosomes, from HeLa-65 cells to the BOT-2 cells, correcting the permease deficiency. Poly-L-ornithine or lipochromes were used for facilitation of chromosome uptake. After selection on HAT medium, transferant clones were isolated at a frequency of 4 x 10(-5) and 1 x 10(-5), respectively. Transferants MGP-1 and MGL-1 are stable after 18 months and have been characterized on the bases of purine and pyrimidine nucleoside uptake, relative thymidine kinase activities, alkaline phosphatase activities, and hydrocortisone-induced alkaline phosphatase activity. MGP-1 demonstrates positive thymidine uptake and incorporates radiolabeled thymidine into DNA. MGL-1 remains thymidine transport-deficient and surveys on HAT by increasing endogenous dihydrofolate reductase activity. Alkaline phosphatase activity in MGL-1 is similar to HeLa-65, 2% of that in BOT-2, and in addition, is inducible 25-30-fold by 3 micro M hydrocortisone. We have separated, genetically, a thymidine permease function from phosphorylation in cells of human origin and have transferred genetic information for the regulation of alkaline phosphatase.

A rare insertional translocation of proximal segment with heterochromatic region of 1q into 7p in monozygotic twins and spontaneous abortions.

We present a family identified through a healthy 20-year-old female with a history of multiple successive spontaneous abortions. Her karyotype demonstrates a rare balanced insertional translocation between chromosomes 1 and 7, 46,XX,dir ins(7;1)(p15.3;q12q21.3). This is the first reported case of a 7;1 insertional translocation involving the proximal segment of chromosome 1 and may well be the cause of the multiple spontaneous abortions in our proband.

A supernumerary microchromosome in amniotic cell cultures and talipes equinovarus in a live born female.

Amniocentesis for advanced maternal age resulted in the demonstration of a supernumerary microchromosome in the amniotic fluid cells. Cytogenetic analysis of peripheral blood from the female infant revealed a mosaic karyotype 46,XX/47,XX, + marker. The only anomaly noted in the infant was talipes equinovarus.

Cytogenetic studies of renal cell carcinoma.

To examine the possibility that patients with renal cell carcinoma (RCC) have chromosomal abnormalities at a common gene locus, we undertook a study of patients with and without a history of hereditary disease as part of an ongoing population-based case-control study of risk factors in RCC. We identified 112 patients for cytogenetic study. Chromosome preparations were made from peripheral blood cultures with standard and giemsa (GTG) banding techniques. C-banding was used to determine C-polymorphism. Eighty-nine cases had completely normal male and female karyotypes. Twenty-seven of them had C-polymorphism. In 16 patients, random numerical and structural abnormalities were observed. In the remaining seven patients, four had mosaic karyotypes, and the other three showed structural abnormalities. There was no statistically significant difference in the frequency of the abnormal karyotypes between the hereditary and nonhereditary RCC patients. This concludes a negative cytogenetic study of RCC patients that failed to show any constitutional rearrangement in blood cells.

Human monoclonal antibodies reactive with antigens of the group A Streptococcus and human heart.

Human mAb were produced from tonsillar or PBL of normal individuals or patients infected with group A streptococci. Lymphocytes were purified on Ficoll-Hypaque gradients and stimulated in vitro with purified group A streptococcal membranes or M protein extracts. The mAb were selected for study based on their reaction with group A streptococci, pep M5 protein, and/or M6 Escherichia coli protein. Further analysis by Western immunoblot or competitive inhibition ELISA revealed that there were two types of antibodies: one type that reacted with myosin and DNA and the other type that reacted with myosin, keratin, and/or actin. The specificities of these human mAb are similar to specificities observed in our previous studies of murine mAb reactive with group A streptococci and heart Ag. For comparison, anti-myosin antibodies were affinity purified from the sera of infected or acute rheumatic fever patients and were shown to react with myosin and DNA as well as with group A streptococci and M protein. To affinity purify these antibodies from normal sera, five times the amount of sera was required to obtain detectable quantities. These data suggest that the human mAb reactive with group A streptococci and myosin reflect the antibodies seen in sera from infected patients or acute rheumatics and that the B lymphocyte clones capable of producing these cross-reactive antibodies are also present in normal individuals.