Biomedical subjects
Publications and source records attributed to H A Gardner.
We describe a variant of carcinoma of the ampulla of Vater, which, to our knowledge, has not been previously described. Classic signet-ring cells represented the predominant cell type, and were admixed with more poorly differentiated tumor cells that were chromogranin positive. These findings raise the possibility of an amphicrine tumor of the ampulla.
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Prenatal diagnosis of del(11)(p13p15) was made on cultured amniotic fluid cells and confirmed on fetal skin fibroblasts after termination of pregnancy. Both irides appeared behind schedule in development by 2-3 weeks in reference to the gestational age of the fetus. It is suggested that the aniridia of the aniridia--Wilms tumour association is due to developmental arrest. Confirmation of this complex is difficult at mid-gestation without critical pathological study of the eyes.
Forty-two adult males--10 with Klinefelter's syndrome (karyotype XXY), 17 with normal sex chromosome karyotype (XY) but with physical signs of hypogonadism, and 15 presumed to be normal both chromosomally and hormonally--completed tests of Verbal and Nonverbal ability. It was predicted: a) that the XXY group would perform more poorly than the other two groups on tests of Verbal ability, and b) that the XY, hypogonadal group would perform more poorly than the others on tests of Non-verbal ability. The first hypothesis was supported. However, in spite of measurable verbal deficits, the XXY men (whose parents were more highly educated than those of the other two groups) did not appear to be underachievers. Rather, they were, in general, as well educated, as likely to be employed, and of socioeconomic status equivalent to that of the other men in the study. These findings are discussed briefly in terms of implications for early childhood education and genetic counselling. The second hypothesis was not supported: this is attributed to presumed heterogeneity of etiology of hypogonadism in the XY, hypogonadal group.
The R3230AC rat mammary adenocarcinoma is a transplantable tumor model, which can be subcultured in vitro and does not metastasize spontaneously. However, when cell suspensions of this tumor are injected intravenously, multiple lung foci develop. These foci were used as source for a cell subpopulation. Prolonged exposure of the original tumor cell line to increasing levels of lectins (concanavalin A and wheat germ agglutinin) resulted in the development of a lectin-resistant subpopulation. Through experimental in vitro exposure to the antiestrogenic compound tamoxifen citrate, a tolerant, karyotypically defined subpopulation was obtained. In the four cell lines studied, heterogeneity was observed in the following parameters: doubling time, steroid receptors, and median chromosome counts. Statistically discernible differences were found. This may represent a model for the effect of selective pressures in the tumor environment, such as endocrine manipulation, leading to the gradual development of resistant cell lines and treatment failure.
Human choriogonadotropin (hCG)-like material has been found in variable amounts on the surface of cells of human and animal tumors. Intravenous injection of R3230 AC rat adenocarcinoma cells, one of the models investigated, results in multiple lung foci seeding. We analyzed the phenotypic diversity of this tumor by cloning and culturing two distinct cell subpopulations from a cell culture of this tumor, hereafter called OR or original cell culture. One was obtained after repeated exposure of the OR to increasing concentrations of concanavalin A and wheat germ agglutinin. A single clone was isolated and was named lectin-resistant (LR) cell line. The LR cells did not metastasize but maintained stable tumorigenicity and morphology over at least 10 passages. A second cell line was obtained by repeated passage and injection of cells from a single metastatic node. After repeating the process five times, a single clone of cells was selected from the final variant and was called lung metastatic (LM) cell line. The LM cultured cells maintained stable tumorigenicity, morphology, and metastatic properties for no more than 10 passages. OR, LR, and LM cells were assessed by their doubling time (DT), chromosome counts, and hCG immunocytochemistry. The results demonstrated that the LM cell line had a higher chromosome count than the LR and the OR cell lines, and its DT was the shortest. Immunocytochemistry of the transplanted OR neoplasm showed scattered expression of the hCG-like material. By the same techniques a complete lack of reactivity of the LR cells was found. However, almost all cells of the LM line were strongly positive for hCG-like material. After a few passages, the great majority of the LM cells also became unreactive. Our data demonstrate: (i) the existence of marked heterogeneity of the expression of hCG-like material in the primary tumor cell population; (ii) that the expression of hCG-like material correlates with the metastasizing capacity of the cells; and (iii) that there is a phenotypic instability for the expression of hCG-like material by tumor cells when maintained in vitro.
Twenty-four cases of fetal cystic hygroma colli were diagnosed by ultrasound. In two patients, the diagnosis was not confirmed at autopsy. Ten of these were cases of Turner's syndrome, one was a case of Turner's mosaicism, three had other aneuploidies, four had normal chromosomes, and six had a failed chromosome culture. The diagnosis, management, and future counseling of these patients are discussed.
The bone marrow of 11 patients with small-cell lung cancer, who survived more than two years following combined-modality therapy, was subjected to morphologic, cytogenetic, and bone marrow culture studies. One patient, after a prodrome of anemia and thrombocytopenia, developed acute leukemia 60 months after the start of chemotherapy. Four months before frank leukemia developed, bone marrow culture studies showed a marked inability to form colonies. Cytogenetic studies demonstrated an abnormal clone of cells that included the deletion of the long arm of chromosome 5. No morphologic abnormalities were noted in the bone marrow of any other long-term survivor; however, the mean corpuscular volume of peripheral red blood cells was greater than normal in three of four patients who remain alive and disease free. In one of these patients marrow culture studies also failed to grow colonies. The other patients showed a decreased ability to form multilineage colonies and colonies of the granulocyte-macrophage lineage in vitro compared with a control population. All patients showed some degree of aneuploidy on cytogenetic analysis; in two cases approximately 50% of cells were aneuploid. However, no clonal abnormality was detected in any patient. Follow-up for the development of secondary acute leukemia and other long-term complications continues in these patients.
We describe a family in which autosomal dominant anterior polar cataracts are segregating in four members over three generations with an apparently balanced reciprocal translocation between chromosomes 2 and 14. We conclude that altered function of a gene or genes on chromosomes 2 or 14 are important in the embryological development of the lens.
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The 46, X, i(Xq) karyotype of isochromosome for the long arm of the X chromosome has been found to be a frequent structural abnormality in Turner's syndrome. To characterize the endocrine, metabolic, and psychometric features of such patients, nine subjects, aged 12 to 49 years, with this specific cytogenetic abnormality were studied. Although eight of the nine patients had a mosaic chromosome pattern, five had a greater proportion of i(Xq) cells than XO cells, and in four of these the proportion of i(Xq) cells was over 80%. Eight of the nine isochromosomes were metacentric and most had a single C-band. Two subjects were hypothyroid, six had thyroid antibodies present and five had parietal cell antibodies. Oral glucose tolerance testing was abnormal in three and elevated insulin levels were present in an additional two subjects. Psychometric testing showed some discrepancy between verbal and performance I.Q. scores, the performance scores generally being lower. Thus, thyroiditis, insulin insensitivity and diabetes mellitus, parietal cell antibodies, and a relatively low performance I.Q. are found in some of the 46, X, i(Xq) Turner's syndrome patients. The highest thyroid antibodies were present in the four subjects in whom more than 80% of cells were 46, X, i(Xq). Two of these subjects also had diabetes mellitus and three had antiparietal cell antibodies. These findings suggest an association of autoimmune disease with this particular cytogenetic abnormality.
A white girl presented at age 16 yr with delayed puberty and primary amenorrhea. She had 46 chromosomes with a de novo reciprocal X;9 translocation. The normal X chromosome was found to be heterochromatic, thus preserving the function of the translocation portion of the 9. Her total estrogen and serum estradiol levels were low and her serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels were at the lower end of the normal adult range. She had a reasonably good FSH and LH response to GnRH, but an inadequate response to 100 mg of clomiphene daily for 1 wk. This would suggest that the abnormality of function is probably hypothalamic, a hitherto unreported association. De novo translocations between X chromosomes and autosomes are rare and none identical to this case has been described. The breakpoint of the X chromosome was at p22, well outside the "critical region" for female reproductive function. It seems probable that her chromosome abnormality is responsible for her clinical state.
There are conflicting reports on the frequency in retinoblastoma tumor cells of aberrations involving chromosome No. 13. To quantitate the frequency of various chromosome aberrations, we analyzed the karyotypes from the retinoblastoma tumors; all tumors contained chromosome abnormalities. Chromosome No. 13 was altered in only two tumors, but the aberrations in these two cases affected different portions of the chromosome. We have concluded that chromosome aberrations affecting chromosome No. 13 are relatively infrequent in retinoblastoma tumors. Chromosome No.1 was involved in rearrangements in eight tumors; in six tumors the rearrangements lead to trisomy of 1q25-1q32. Seven tumors had aberrations resulting in trisomy of the long arm of chromosome No. 17; the most common aberration was an i(17q) chromosome. Every tumor showed trisomy of the long arm of either chromosome No. 1 or 17. These changes in chromosomes No. 1 and 17 have been observed by others in many different tumors and are not unique to retinoblastoma. In summary, chromosome abnormalities were present in all retinoblastoma tumors studied, but no aberration common to all tumors was found.
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The numerous inherited disorders involving the head and neck are best understood against the background of Mendelian genetics. An appreciation of patterns of inheritance and the factors that modify or simulate then allows the clinician to weigh the importance of family history, to evaluate the basic mechanisms involved in the disorder, and to give advice concerning future generations.
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The autopsy of an infant with the 4p- or Wolf-Hirschhorn syndrome revealed visceral abnormalities not previously described, i.e., agencies of the gallbladder and spleen. The parents' chromosomes were normal.