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Biomedical subjects

H Coon

Publications and source records attributed to H Coon.

9 recordsLinked to original sources

Continuous culture of neuronal cells from adult human olfactory epithelium.

Cells from the olfactory epithelium of adult human cadavers have been propagated in primary culture and subsequently cloned. These cells exhibit neuronal properties including: neuron-specific enolase, olfactory marker protein, neurofilaments, and growth-associated protein 43. Simultaneously, the cells exhibit nonneuronal properties such as glial fibrillary acidic protein and keratin, the latter suggesting properties of neuroblasts or stem cells. These clonal cultures contain 5-10% of cells sufficiently differentiated to show odorant-dependent cyclic adenosine 3',5'-monophosphate (cAMP) or calcium-release responses when challenged with submicromolar concentrations of odorants. The potential of culturing neuronal cells from patients with neuropsychiatric disorders, such as Alzheimer's disease or schizophrenia, could enable the study of the pathophysiology of these neurons in the culture dish and allow new approaches to the study of mental illness.

Adult

Identifying children in the Colorado Adoption Project at risk for conduct disorder.

Clustering techniques were used to identify a subsample of young adopted and nonadopted children in the Colorado Adoption Project at risk for conduct disorder. Although data from both boys and girls were analyzed, a cluster of girls large enough for subsequent statistical analysis could not be identified; therefore, results are reported for boys only. Identifying measures were selected based on the DSM-III-R diagnostic criteria. Cluster analyses confirmed the existence of a small group of boys who appeared to be significantly at risk. Subsequent parental and teacher ratings of these children verified the stability over time of the classification. The poor conduct group was significantly associated with difficult temperament in infancy, with poor conduct on the part of parents when they were youths, and with high achievement orientation in the home environment.

Adoption

Parent-offspring and sibling adoption analyses of parental ratings of temperament in infancy and childhood.

A first step toward understanding the etiology of personality is to investigate the relative impact of genetic and environmental factors using twin and adoption designs. Twin studies of infants and young children indicate substantial genetic influence for parental ratings of temperament in the preschool years. Adoption studies, however, have not previously been reported during the early years of life. We present parent-offspring comparisons for temperament (emotionality, activity, sociability, and impulsivity) for adopted and nonadopted children yearly from 1 to 7 years of age and their biological, adoptive, and nonadoptive parents. Also presented are correlations for adoptive and nonadoptive siblings when each child was 1, 2, 3, and 4 years of age. In contrast with twin results, little evidence is found for genetic influence. The average correlation between biological parents and their adopted-away children for data averaged over the 7 years is only .03. Similarly, the average parent-offspring correlation in nonadoptive families (.08) is no greater than in adoptive families (.12). Results for nonadoptive and adoptive siblings also indicate little genetic influence. The difference between the twin and adoption results may be due to environmental effects or to nonadditive genetic variance.

Adoption

A simple method of model fitting for adoption data.

Traditional models used with adoption data often make strong assumptions concerning the nature of genetic transmission and assortative mating. A simple model is presented which avoids these assumptions. The model is linearized and, thus, has the further advantage that it can be used with standard statistical packages such as LISREL or EQS. The model allows tests of the internal consistency of the data, in addition to tests of the relative strength of genetic and environmental transmission parameters. To illustrate the model, measures of general cognitive ability in parents and their 7-year-old children from the Colorado Adoption Project (CAP) were fit to the model using the LISREL program. This relatively simple model may be expanded to incorporate more complex designs involving multiple measures or siblings. Although the model will not always allow constraints on the parameter estimates in more complex models, it offers a quick, flexible method for initial exploration of adoption data.

Adoption

Genetic and environmental determinants of musical ability in twins.

Analyses of musical ability data from the Loehlin and Nichols National Merit Scholarship study are presented. Musical ability is indexed by four measures: interest in a profession in music, performance in school, performance outside of school, and receiving honors in music. These variables pose a challenge for behavior genetic analysis since they do not conform to the assumptions of traditional linear models. For example, there is a dependent relationship between the honors and the performance variables; one cannot obtain honors without performance. Several methods were employed to deal with these relationships, and the following conclusions appeared regardless of the method used. First, twin correlations were always high, ranging from 0.44 to 0.90 in monozygotic (MZ) twins and from 0.34 to 0.83 in dizygotic (DZ) twins. Second, although there was evidence for heritable variation, the effects of common environment were almost always larger than the effects of heredity. Third, marital assortment was not of sufficient magnitude to account for these common environment effects. In the young adults in this sample, musical ability is influenced more by shared family environment than by shared genes.

Adolescent

High NaCl induces stable changes in phenotype and karyotype of renal cells in culture.

Extracellular fluid in the renal medulla normally is hyperosmotic. To test adaptation to such an environment, a continuous line of rabbit renal inner medullary epithelial cells (GRB-PAP1), which had been established in isosmotic medium, was switched to a medium containing high NaCl. The origin of these cells is described. When the osmolality was raised from 300 to 600 mosmol/kg by adding NaCl, cells eventually survived and proliferated, but unexpectedly, they underwent major changes in phenotype and karyotype that persisted during proliferation in isosmotic or hyperosmotic medium for at least 7 months. The threshold concentration for the changes was approximately 500 mosmol/kg. Cells of a typical strain (PAP-HT25) that formed in hyperosmotic medium were much larger and more often multinucleated than were GRB-PAP1. GRB-PAP1 cells were near diploid; PAP-HT25 cells were polyploid. The changes, since they occurred in most clones, were due to adaptation of the majority of cells and not to selection of a minority of cells already having these characteristics. Cloning efficiency was higher for GRB-PAP1 than PAP-HT25 in isosmotic medium, but the reverse occurred in hyperosmotic medium. Thus exposure to the hyperosmotic medium induced greater ability to clone in it. We suggest that these changes may involve persistent alterations in gene regulation, possibly like those previously reported in chicken embryo fibroblast cells after hyperosmotic NaCl (Cell 30: 131-139, 1982).

Animals

Reconstruction of a thyroid gland equivalent from cells and matrix materials.

A living thyroid gland equivalent has been fabricated with a cultivated strain of rat thyroid cells (FRTL), dermal or thyroid fibroblasts, and matrix materials. The mixture becomes tissuelike in vitro by virtue of interactions between fibroblasts and collagen. Initially in vitro the thyroid cells are uniformly distributed as single cells and a small number of clusters containing less than 10 cells. When implanted into thyrodectomized hosts the thyroid cells in the tissue lattice become organized into follicles containing a colloidlike material. The follicles were found in clusters in sizes up to 0.3 mm. The clusters are vascularized. It is thought that they arise within clones rather than by an aggregation process. Using an antithyroglobulin antibody it was shown that both thyroid cells and the colloidlike material within follicles reacted positively. Development of follicles was strictly dependent on whether hosts were thyroidectomized. In nonthyroidectomized hosts no follicles were observed. We conclude that an organotypic structure can develop in vivo from a "gland-equivalent" fabricated with adult cells and matrix materials combined in vitro, and that cells cultivated for years in vitro retain the capacity to express differentiated functions in a reconstituted organ equivalent in vivo.

Animals

Cloning of infectious adeno-associated virus genomes in bacterial plasmids.

We describe the construction of two Escherichia coli hybrid plasmids, each of which contains the entire 4.7-kb DNA genome of the human parvovirus, adeno-associated virus (AAV) type 2. Because the AAV genome was inserted into the plasmid DNA using BglII linkers the entire virus genome can be recovered by in vitro cleavage of the purified recombinant plasmid. Transfection of these recombinant DNAs into an adenovirus-transformed human cell line in the presence of helper adenovirus resulted in efficient rescue and replication of the AAV genome and production of fully infectious virus particles. These AAV-plasmid recombinant DNA molecules should be useful both for site-specific mutagenesis of the viral genome and to study the potential of AAV as a eukaryotic vector.

Adenoviruses, Human

Oncogenic transformation of murine lymphoid cells by in vitro infection with Abelson leukemia virus.

Spleen cell cultures stimulated to DNA synthesis by antigen or mitogen were infected with Abelson virus, a C-type RNA virus inducing nonthymic lymphomas in mice. After 3 days the cells were transferred to mice and caused 100 percent incidence of lymphomas in as few as 29 days. That a number of the tumors were of donor origin, as shown by female karyotypes in recipient male mice, indicated that cells infected by virus in vitro were transformed. The process depended upon both virus and stimulation of lymphocytes in culture. Lymphoid tumors did not develop in mice receiving cells from virus-infected cultures not exposed to antigen or mitogen.

Animals