Leonard Atkins

Etiologic Heterogeneity of Neural-Tube Defects

We classified 106 stillborn and live-born infants with anencephaly, meningomyelocele, meningocele and encephalocele according to the recognized causes of these malformations. Six different causes were identified, including both genetic and nongenetic disorders; 12 per cent had nongenetic disorders, a chromosome abnormality, or an encephalocele as part of the autosomal recessive Meckel syndrome. Therefore, for this 12 per cent genetic counseling normally provided for isolated anencephaly, meningomyelocele or encephalocele would have been incorrect. If all infants were considered together regardless of cause, the precurrence and recurrence rates of similar malformations in the sibs were 5.2 and 1.7 per cent respectively. However, if infants with other disorders, especially the Meckel syndrome, were excluded, the precurrence and recurrence rates for isolated anencephaly, meningomyelocele and encephalocele among white infants were only 1.7 per cent and 0 per cent. These rates are much lower than the risk of 5 per cent currently being used in genetic counseling in the United States.

Familial Premature Ovarian Failure Due to an Interstitial Deletion of the Long Arm of the X Chromosome

Abstract We describe a family in which four women had menstrual irregularities and a partial deletion of the long arm of the X chromosome (Xq). Three of the four women had premature ovarian failure (at the ages of 24 to 37 years). Chromosome-banding studies initially suggested that a terminal portion of Xq was deleted. However, DNA-hybridization studies showed that an interstitial portion of Xq was deleted and that the affected women had a 46,XX,del(X)(pter-q21.3::q27-qter) karyotype. These findings help clarify the role of Xq in ovarian function and indicate that the accurate description of such abnormalities requires a combination of cytogenetic and DNA-hybridization analysis. (N Engl J Med 1987; 317: 125–31.)

A Case of Trisomy 9

The first patient with trisomy 9, an infant who survived 28 days, is reported. Clinical findings included microcephaly, low-set malformed ears, small palpebral fissures, enophthalmos, bulbous nose, micrognathia, low hairline, congenital heart disease, skeletal abnormalities, small penis, hypoplastic scrotum, and a Dandy-Walker like deformity of the fourth ventricle.

KLE: a cell line with defective estrogen receptor derived from undifferentiated endometrial cancer.

KLE is a cell line derived from a poorly differentiated endometrial carcinoma that is aneuploid with chromosome numbers ranging from 51 to 66 and 6-8 marker chromosomes demonstrated by G banding. Tumors harvested from five of five nude mice bearing an inoculum for more than a month resemble the original specimen, and electron microscopy shows microvilli, many junctional processes, glycogenation, and a prominent nucleolonema. The cell cytosol contains a specific binder for estradiol, but there is no estrogen receptor in the nucleus and in a study reported elsewhere (Raam et al., Breast Cancer Res. Treat. 2, 277 (1982) ) translocation to the nucleus fails to occur. The enzyme phenotype of this cell is human, non-HeLa.

Amplification of AML1 in childhood acute lymphoblastic leukemias.

Amplification of AML1 has been confirmed by fluorescence in situ hybridization analysis in two cases of childhood acute lymphoblastic leukemia. It remains to be elucidated whether this amplification results in up‐regulation of the normal AML1 gene product or a potentially mutant AML1 transcript.

Correlation of Gross Gastroscopic Findings with Gastroscopic Biopsy in Gastritis

THE development of the Wolf-Schindler flexible gastroscope in 19321 followed by the Benedict flexible operating gastroscope in 19482 and the flexible gastric-biopsy tube invented in 1949 by Wood et...

Characterization of a xenograft model of human ovarian carcinoma which produces intraperitoneal carcinomatosis and metastases in mice.

A new xenograft model for human epithelial ovarian carcinoma with extensive intraperitoneal (i.p.) carcinomatosis as the predominant disease manifestation, is described. Cells from the established NIH:OVCAR‐5 cell line were injected i.p. into 6‐to 8‐week‐old Swiss nude mice. Comparative analyses between cells cultured in vitro and tumor cells derived ex vivo were performed to assess histologic features, immunohistochemical cell markers, hormonal receptor expression, adhesion to extracellular matrix molecules and chromosomal constitution. Macroscopically, the extent of tumor development appeared to be site‐dependent and tumor cell survival was dose‐dependent. Advanced disease was characterized by extensive solid tumor burden and ascites with parenchymal invasion, lymphatic metastases and vascular dissemination. Individual tumor nodules exhibited developing neovasculature characterized by the absence of mature basement membrane. Despite some histologic loss of cellular differentiation in advanced disease, antigenic expression was preserved, distinguishing these cells as epithelial in origin. Karyotyping of tumor cells demonstrated multiple numeric and structural chromosomal abnormalities. Serum and ascites CA 125 levels were consistently elevated only in tumor‐bearing mice. This new murine model closely resembles the aggressive disease process of human epithelial ovarian carcinoma, in which the efficacy of i.p. and systemic therapeutic modalities can be investigated.

Prenatal genetic diagnosis. 3.

More than 100,000 children are born in the U.S. each year with major congenital defects or genetic disorders, with or without mental retardation. Advances in prenatal diagnosis have now made it possible to detect an increasing number of these disorders in utero. Carrier detection is advised prior to pregnancy, rather than after the birth of a defective child, or during pregnancy itself. Patients have a right to know about their genetic risks and should have the freedom to exercise their options.

CHROMOSOMAL HETEROMORPHISM IN SOME MALE LIZARDS OF THE GENUS ANOLIS

Chromosomal heteromorphism in males of several species of the lizard genus Anolis is demonstrated. In the bimaculatus group, the diploid number of chromosomes is 29 in males and 30 in females. Males have three unpaired chromosomes--an acrocentric, a microchromosome, and a metacentric. These are interpreted as X1, X2, and Y, respectively. Females are characterized as X1X1X~2X2. In A. conspersus the male has a heteromorphic pair of macrochromosomes (one member is acrocentric, one member metacentric). The diploid number is 30. No female was available. A. biporcatus has a mechanism that appears identical to the bimaculatus group. The diploid number for males is 29, for females 30. Males have three unpaired chromosomes--an acrocentric, a microchromosome, and a metacentric. Males are X1X2Y, females are X1X1X2X2.

Eosinophilia, chloromas and a chromosome abnormality in a patient with a myeloproliferative syndrome

The existence of eosinophilic leukemia remains controversial since many authors challenge the existence of this entity. We present a patient with a hypereosinophilic syndrome whose findings were consistent with a leukemic process. The patients course was marked by signs and symptoms of myeloblastoma formation and his illness terminated in an acute blastic crisis. Chromosome studies on peripheral blood leucocytes demonstrated aneuploidy and an abnormal number four chromosome with additional material on its long arm. This case appears to be an unusual example of a hypereosinophilic syndrome with both myeloblastoma formation and an abnormal leucocyte karyotype.