Anterior mediastinal mass in a young man.

The case is presented of a patient in whom the diagnosis of Klinefelter's syndrome was made only after a mediastinal teratoma was discovered. Chest physicians should be aware of this association since they are often the first to evaluate patients with mediastinal masses.

Neuroblastoma as a prominent component of a mixed germ cell tumor of testis.

BACKGROUND: Primitive neuroectodermal tissue in teratomas of testis has been reported in the literature. A mixed germ cell tumor of testis with a prominent neuroblastoma component dictating the clinical behavior was found to be unique. METHODS: Tissue sections were stained with hematoxylin and eosin, and immunohistochemical, ultrastructural, cytogenetic, and flow cytometric analyses were performed on the primitive neuroectodermal component of the testicular mass. Follow-up results at 2.5 years are included. RESULTS: The microscopic findings on hematoxylin and eosin slides showed cells composing the majority of the neoplasm to have features of neuroblastoma. The immunohistochemical stains showed positivity for neuron-specific enolase in the cells comprising the neuroblastoma, and transmission electron microscopic study corroborated these findings by demonstrating microtubules and rare membrane-limited, dense-core granules in the cytoplasm. Flow cytometry showed a hypertetraploid population with a large aneuploid DNA content. Cytogenetics revealed a hypertriploid modal number of 74 chromosomes. The clinical features were dictated by the neuroblastoma component in a fashion similar to that of adult neuroblastomas and responded to the chemotherapeutic regimen designed for treating neuroblastoma. CONCLUSIONS: The neuroblastoma component proved to be more aggressive than the other elements of this neoplasm. This finding suggests that mixed germ cell tumors showing a large neuroblastoma component should be treated promptly and aggressively with chemotherapy.

Growth-dependent expression of human Mr 53,000 tumor antigen messenger RNA in normal and neoplastic cells.

We have investigated the expression of Mr 53,000 protein (p53) in total RNA isolated from human peripheral blood mononuclear cells stimulated by phytohemagglutinin, in serum-stimulated human diploid fibroblasts, and in normal and tumor cells of human epithelial colon tissue. We have found that the expression of p53 messenger RNA is growth regulated in human cells following kinetics similar to that previously shown in mouse 3T3 cells, and is increased in the large majority of colon adenocarcinomas in comparison to adjacent normal mucosa and adenoma. This increased expression of p53 is accompanied by a nearly proportional increase in the expression of histone H3. As the expression of histone H3 is restricted to the S phase of the cell cycle and therefore measures the growth fraction of a given population, we suggest that the increased expression of p53 observed in the large majority of colon tumors simply reflects the increased number of cycling cells frequently found in a neoplastic tissue. At variance with these findings a true overexpression of p53 was detected in one SV40-transformed human fibroblasts cell line.

Fetal cystic hygroma and Turner's syndrome.

Large nuchal cystic hygromas were observed in five second-trimester aborted fetuses at autopsy. Two female fetuses with generalized edema were karyotyped as 45,X. One of these was the twin of a 46,XX normal female sibling. The association of generalized edema with large nuchal cystic hygromas was seen only in these two fetuses and represents strong phenotypic evidence of Turner's syndrome. However, the absence of hydrops was not a reliable indicator of normal karyotype. One fetus without generalized edema was karyotyped as 47,XY, +21, inv(9). The remaining cases had normal karyotypes. Placental histology was not useful in discriminating monosomy X from other conditions, but placental tissue culture was important in obtaining a cytogenetic diagnosis. Karyotyping is recommended in all cases of fetal cystic hygroma.

Expression of c-myc and other cell cycle-dependent genes in human colon neoplasia.

We have investigated the expression of certain cell cycle-dependent genes in total RNA isolated from normal and neoplastic cells of human epithelial colon tissue. The genes studied had been previously identified as cell cycle dependent in rodent and human fibroblasts. Levels of expression of G1 genes were compared to the level of expression of the S-phase-specific gene H3 in normal and adjacent neoplastic epithelial cells of six different individuals. We have found that the increase in the expression of c-myc gene detected in colon tumor cells is accompanied by a parallel increase in the expression of two G1-specific genes (p2A9 and ornithine decarboxylase) and the S-phase-specific gene histone H3. An important conclusion that can be drawn from these findings is that the increased level of a cell cycle-specific RNA in a tumor may not indicate overexpression of that gene but simply reflect the increased fraction of cycling cells, unless the ratio of expression between G1 genes and G1-S-phase genes is altered.

Pregnancy in the Turner syndrome with only 45,X chromosomal constitution.

A 31-year-old white female, 127 cm tall and with other findings of the Turner syndrome, had had normal menses and had become pregnant at ages 23 and 26 years. Chromosomal analyses of several tissues, including both ovaries, revealed only 45,X karyotypes. Both of her daughters had 46,XX karyotypes in lymphocytes. This patient and nine other reported cases of fertile, apparently nonmosaic 45,X women illustrate an extreme of ovarian function in the Turner syndrome and raise questions about the absolute need for XX oocytes in ovarian development. The possibility of pregnancy must be considered in all patients with Turner syndrome, a relatively common chromosomal disorder.

Familial occurrence of chromosome 7/12 translocation.

A new balanced translocation, t(7;12) (p12;p13), was found in a high genetic risk family in which the mother is a translocation carrier. She had 12 pregnancies, six of which were terminated during the first trimester by spontaneous abortions. Among the six live births, three children inherited the translocation from their mother and were phenotypically normal. The father and three other children had normal karyotypes.

Clinical and cytogenetic studies of patients with polycystic ovary disease.

Chromosomal studies in patients with polycystic ovary disease have produced contradictory findings. Whereas some patients showed various sex-chromosome anomalies, the majority had a normal karyotype. However, banding techniques were not employed in any of those studies. This report presents the result of cytogenetic studies with the use of the trypsin-Giemsa banding technique in 15 patients with polycystic ovary disease. Ten patients had normal karyotypes. In five patients, pseudodiploidy with trisomy 14 was present in 2% to 4% of the cells analyzed. However, the missing chromosome in pseudodiploid cells was not always the same. The phenotype of these patients was normal, except for polycystic ovary disease. The finding of trisomy 14 in 2% to 4% of the cells in five of 15 patients (33%) with polycystic ovary disease is significant, since such an occurrence is extremely rare in the general population. The implication of this cytogenetic finding remains unclear.

Association of human chromosome 14 with a ts defect in G1 of Chinese hamster K12 cells.

Somatic cell hybrids between human lymphoblastoid cells (Raji) and temperature-sensitive Chinese hamster cells (K12) were selected from monolayer cultures in MEM at 40 degrees C. A total of 21 hybrid clones were isolated and karyotyped. All clones contained a near complete set of Chinese hamster chromosomes and 1 to 5 human chromosomes. Human chromosome 14 present in the hybrid cells of all clones; and was the only human chromosome retained in 10 clones. The presence of human chromosome 14 in hybrids was further confirmed by the demonstration of human nucleoside phosphorylase activity in the hybrid cells. Only one hybrid clone was positive for EBNA, the Epstein-Barr virus antigen present in Raji cells. These findings indicate that human chromosome 14 contains the necessary information for the K12 cells to overcome their G1 defect in the cell cycle and grow at non-permissive temperature. The present study lends strong support to the possibility that different steps in the G1 phase of the cell cycle are controlled by genes located on different chromosomes.

Temperature-sensitive variants for saturation density and anchorage dependencey of a simian virus 40-transformed human X mouse hybrid cell line.

Several variant clones temperature sensitive for some parameters of transformation from a hybrid cell line containing a stable diploid mouse genome and two human chromosomes 7 carrying an integrated defective simian virus 40 have been isolated. Like the wild-type (wt) cells, at the permissive temperature the temperature-sensitive (ts) clones grew to high saturation densities and readily formed colonies in methyl cellulose. In contrast to the wt cells, at the nonpermissive temperature they had variable but always lower saturation densities and were unable to form colonies in methyl cellulose. The fraction of cells that synthesized DNA decreased at both temperatures when the cells reached saturation density, but it represented always at least 20% of the total population. All of the ts clones so far tested had a near triploid chromosome number, contained from one to three human chromosomes 7, and were T-antigen-positive both at the permissive and nonpermissive temperatures. The ts clones maintained low saturation density at the nonpermissive temperature because of a decrease in the number of cells that were actively proliferating and because of the shedding of cells into the medium. Temperature downshifts and refeeding allowed for expression of the permissive phenotype. In most of the isolated clones anchorage independency was not correlated with unrestricted cell proliferation. These variant clones may provide useful systems for a better understanding of the number of interdependent pathways involved in the expression of the phenotype of a transformed cell and elucidate the molecular mechanism required for the maintenance of a normal state in a cell population.

Chromosome 6/15 translocation with multiple congenital anomalies.

A female infant with multiple congenital anomalies was found to have an abnormal karyotype: 45,XX,--6,--15, +t (6;15). Precise identification of the translocation was made by trypsin-Giemsa banding technic. The congenital malformations include hypertelorism, microphthalmia, beak nose, low-set ears, cleft palate, micrognathia, simian crease, hypertrichosis, and low hairline. The unbalanced translocation is apparently responsible for the abnormal phenotype.

The role of nuclei and nucleoli in the control of cell proliferation.

A number of changes have been reported to occur in chromatin of quiescent cells stimulated to proliferate. These changes, indicative of increased transcriptional activity, occur in the early prereplicative phase, several hours before the onset of DNA replication, and are detectable not only in chromatin, but also in isolated nuclei and in whole cells. Most of the increased transcriptional activity can be attributed to an increased activity of the nucleolus; however, extranucleolar genes are also important in the regulation of the cell cycle flow, from G0 to S.

Cytogenetic variants in holoprosencephaly. Report of a case and review of the literature.

A new infant with classical features of holoprosencephaly and multiple extracranial malformations was found to have abnormal karyotype: 47, XX, + 13. Although trisomy D has been reported in a few cases, our case is the first, to our knowledge, in which positive identification of trisomy 13 was made by banding technique in cebocephaly.

Release by human chromosome 3 of the block at G1 of the cell cycle, in hybrids between tsAF8 hamster and human cells.

A temperature-sensitive mutant of Syrian hamster cells, AF8 was fused with simian-virus-40-transformed Lesch-Nyhan fibroblasts; LNSV, in the presence of beta-propiolactone-inactivated Sendai virus. The AF8 cells grow well at 33.5 degrees but are arrested in mid G1 period when shifted to 39 degrees. The LNSV cells are deficient in hypoxanthine guanine phosphoribosyltransferase. The hybrid clones were selected in hypoxanthine-aminopterin-thymidine medium at 39 degrees. A total of 20 clones was isolated and karyotyped. All clones contained most of the hamster chromosomes and one to eight human chromosomes. The preferential retention of human chromosome 3 was observed in 100% of the metaphases of all clones. In nine of the clones, the only human chromosome present was chromosome 3. The results indicate that human chromosome 3 is responsible for conferring to the hybrid cells the ability to grow at nonpermissive temperature for AF8 cells, i.e., the ability to overcome the G1 block. These findings, together with other reports in the cell cycle may be regulated by genes located on different chromosomes.

Neonatal lupus erythematosus. Report of four cases with review of the literature.

We report four newborn infants with a distinctive evanescent cutaneous eruption that clinically and histologically resembled lupus erythematosus; two of the mothers had undifferentiated connective tissue disease. The tendency for lesions to occur in a periorbital location and the association of prominent telangiectasias were characteristic clinical signs in our patients. Immunoglobulin deposition at the basement membrane was demonstrated in one patient. Cytogenetic studies, done to exclude Bloom syndrome, revealed only nonspecific chromosomal abnormalities. A brief review of the literature, with speculations on the possible relationship of these changes to the occurrence of connective tissue disease in the mothers, is included in the discussion.