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Biomedical subjects

C S Cooper

Publications and source records attributed to C S Cooper.

At least 127 records · Page 7Linked to original sources
PubMed1987

Variables associated with disrupted placement in a select sample of abused and neglected children.

The purpose of this study was to examine the placement history of 172 abused and/or neglected children who had been placed in a residential home for maltreated children. Data were collected on the child's placement history (i.e., number of placements, time in transition, and placement rate) and also on child and family characteristics. Pearson correlation coefficients were run between child and family variables and each of the three placement history variables. In addition, t-tests were also used as a method of analysis. Results indicated that children with the following characteristics or life circumstances experienced the more disruptive experience while in foster care: children having severe behavior problems; children who were very young when first removed from their natural home; and children having drug addicted and/or alcoholic parents. Implications of these findings indicate social workers and judges need to be alert to the potential for system abuse of children in foster placement, responsible long-term planning for any child in foster care is critical, and those involved in therapeutic treatment for abused/neglected children should be attentive to the child's placement history.

Adolescent↗
PubMed1987

Induction of thymomas by N-methyl-N-nitrosourea in AKR mice: interaction between the chemical carcinogen and endogenous murine leukaemia viruses.

AKR mice develop thymomas spontaneously when greater than 6 months old but when young AKR mice are treated with N-methyl-N-nitrosourea (MNU) they develop thymomas at 3-6 months of age. In this study the potential role of oncogene activation in the development of both the spontaneous and MNU-induced thymomas in AKR mice has been examined by DNA transfection into NIH3T3 mouse fibroblasts and by Southern analysis of tumour DNA. The results show that a high proportion of MNU-induced thymomas contain activated cellular rasK while no activated cellular ras genes were detected in spontaneous thymomas. Southern analysis of tumour DNA revealed that 2/30 spontaneous tumours and 2/52 MNU-induced tumours contained alterations in the c-myc gene while 5/29 spontaneous tumours and 6/56 MNU-induced tumours contained alterations in the Pim-1 gene. A more detailed analysis of the Pim-1 gene demonstrated that the alterations observed in most MNU-induced and spontaneous tumours resulted from proviral integration at the 3' end of this gene. Our analyses also demonstrated that the majority of MNU-induced tumours, including those containing rearrangements in the Pim-1 gene, lacked the somatically acquired recombinant MCF proviruses that are present in most spontaneous AKR lymphomas. These results provide evidence that the mechanisms of development of MNU-induced and spontaneous tumours in AKR mice are distinct and the development of thymomas that contain proviral integrations at the Pim-1 locus in the MNU-treated AKR mice involve cooperation between the chemical carcinogen and endogenous murine leukaemia viruses.

Animals↗
PubMed1987

Primary structure of the met protein tyrosine kinase domain.

The primary structure of the protein tyrosine kinase domain of the human met gene has been determined from cDNA clones prepared from transcripts of the activated human met gene. These analyses reveal that the met kinase domain (located on human chromosome 7) possesses unique features that distinguish met from other members of the src family of protein tyrosine kinases. The results also demonstrate that the product of the activated met gene is a fusion protein and that the amino terminal end of this fusion protein, which is encoded by human chromosome 1, exhibits homology to laminin B1.

Amino Acid Sequence↗
PubMed1986

The activated human met gene encodes a protein tyrosine kinase.

We have raised antibodies against a synthetic dodecapeptide corresponding to the carboxyl terminus of the predicted met gene product. Phosphorylation of 60 kDa and 65 kDa proteins on tyrosine residues was observed when immunoprecipitates of cells containing the activated human met gene were incubated with [gamma-32P]ATP. Phosphoproteins with the same molecular masses could be immunoprecipitated from cells metabolically labelled with [32P]orthophosphate. When considered together, these observations indicate that the activated human met gene encodes 60 kDa and 65 kDa proteins that can catalyse autophosphorylation on tyrosine residues.

Amino Acid Sequence↗
PubMed1986

Chromosome mediated gene transfer of six DNA markers linked to the cystic fibrosis locus on human chromosome seven.

The DNA probes met and pJ3.11 are derived from loci on chromosome seven that are closely linked to, and probably flanking, the gene mutation causing cystic fibrosis (CF). We have shown that mitotic chromosomes from the cell line MNNG-HOS, which contains an activated met oncogene, can induce morphological transformation of mouse NIH-3T3 cells. Southern analysis of isolated transfectant cell lines with cloned dispersed repetitive human DNA sequences as probes demonstrated that several lines of transformed NIH 3T3 cells had stabley incorporated large segments of chromosome seven DNA. Southern blot analysis also demonstrated the presence of met, pJ3.11 and several other single copy sequences that had been previously localised to chromosome 7 within the transgenomes. In this way a further four genetic markers were shown to be physically linked to met, and thus to CF. These probes may prove useful in confirming the order of loci around CF and in the prenatal diagnosis of this common autosomal recessive disease.

Animals↗
PubMed1986

Mechanism of met oncogene activation.

The met oncogene activated in vitro by treatment of a human osteogenic sarcoma (HOS) cell line with N-methyl-N'-nitronitrosoguanidine (MNNG) is related to the tyrosine kinase gene family. Probes from the met oncogene locus recognize two distinct transcripts of 9.0 kb and 10.0 kb which are independently expressed in a cell-type-specific fashion. While the met proto-oncogene locus expresses the 9.0 kb RNA and maps to human chromosome 7q21-31, the locus expressing the 10.0 kb RNA, (tpr; translocated promoter region) maps to human chromosome 1. Both MNNG-HOS cells and met NIH 3T3 transformants express a novel 5.0 kb RNA which represents a hybrid transcript with 5' sequences derived from tpr and 3' sequences from the met proto-oncogene. Treating HOS cells in vitro with MNNG, a known clastogenic carcinogen, resulted in fusion of two chromosomally disparate loci, met and tpr, generating the active met oncogene.

Cell Line↗
PubMed1986

Amplification and overexpression of the met gene in spontaneously transformed NIH3T3 mouse fibroblasts.

We have identified a class of transformed NIH3T3 mouse fibroblasts that arise at low frequencies in transfection experiments with DNA from both neoplastic and non-neoplastic cells and that may result from a low level of spontaneous transformation of NIH3T3 cells. DNA from the transformed cells was unable to transform NIH3T3 cells in a second cycle of transfection and, where examined, the cells showed no evidence for the uptake of the transfected DNA sequences. The results of Southern analyses demonstrate that a mouse homologue of the human met oncogene is amplified 4- to 8-fold in 7 of 10 lines of these transformed NIH3T3 mouse fibroblasts. The cells containing the amplified gene also exhibit at least a 20-fold overexpression of an 8.5-kb mRNA that is homologous to met. To test the hypothesis that met encodes a growth factor receptor, we examined the binding of platelet-derived growth factor, epidermal growth factor, insulin-like growth factor I and gastrin-releasing peptide to transformed and non-transformed NIH3T3 cells. The results show that there is no significant elevation of the binding of these growth factors to cells containing amplification and overexpression of met.

Animals↗
PubMed1986

The chemistry of lipid peroxidation metabolites: crosslinking reactions of malondialdehyde.

Malondialdehyde reacts readily with amino acids to form adducts containing vinylogous amidine linkages. Crosslinking reactions between nucleic acid bases and amino acids induced by malondialdehyde also have been investigated. The physical data obtained for the adducts provide structural information on the possible mode of crosslinking of proteins and nucleic acids induced by this lipid metabolite.

Chemical Phenomena↗
PubMed1985

Metabolic activation of 7,12-dimethylbenz[a]anthracene in rat mammary tissue: fluorescence spectral characteristics of hydrocarbon-DNA adducts.

The hydrocarbon-deoxyribonucleoside adducts present in DNA isolated from the mammary glands of rats that had been treated with 7,12-dimethylbenz[a]anthracene (DMBA) were separated by Sephadex LH20 column chromatography, purified by high performance liquid chromatography (HPLC), and examined by photon-counting spectrophotofluorimetry. The adducts were found to have anthracene-like fluorescence spectra which is consistent with the reaction of diol-epoxides formed in the 1,2,3,4-ring of DMBA with mammary gland DNA.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1984

An activated rasN gene: detected in late but not early passage human PA1 teratocarcinoma cells.

Early passages of the human teratocarcinoma cell line PA1 are not tumorigenic in nude mice, while late passages are. A transforming gene present in late passages of PA1 cells was isolated as a biologically active molecular clone and is a new isolate of the human rasN locus. Its transforming activity is due to a single G---A (G, guanine; A, adenine) point mutation at the codon for amino acid 12 which changes the codon for glycine so that an aspartic acid residue is expressed. In contrast to late passage PA1 cells (passages 106, 330, and 338), DNA from the PA1 cell line at early passages (passage 36) does not yield rasN foci in DNA transfection assays. Thus, the presence of an activated rasN in PA1 cells correlates with enhanced tumorigenicity of the cell line and, more importantly, may have arisen during cell culture in vitro.

Animals↗
PubMed1984

Characterization of human transforming genes from chemically transformed, teratocarcinoma, and pancreatic carcinoma cell lines.

Dominant transforming genes that were transferred to mouse NIH3T3 cells by cellular DNAs prepared from a chemically transformed human cell line (MNNG-HOS), a human teratocarcinoma cell line (PA1), and a human pancreatic carcinoma cell line (A1165) were characterized (a) analyzing the repetitive human DNA sequences that were associated with the transforming gene and (b) determining their relationship to the oncogenes of the Harvey (rasH) and Kirsten (rasK) sarcoma viruses and to the human neuroblastoma transforming gene (rasN). The results show that the transforming gene activated in the teratocarcinoma cell line is identical to the neuroblastoma transforming gene and that the transforming gene of the pancreatic carcinoma cell line is a human homologue of rasK. In contrast, the transforming gene activated in the chemically transformed human cell line showed no detectable homology to rasK, rasH, and rasN.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1983

Sites of single-strand breaks in DNA treated with a diol-epoxide of benz[a]anthracene.

Evidence presented here indicates that r-8,t-9-dihydroxy-t-10,11-oxy-8,9,10,11-tetrahydrobenz[a]anthracene can introduce single-strand breaks into DNA. The positions of the single-strand breaks were determined in experiments in which the diol-epoxide was incubated with a defined 85 base pair DNA molecule that was radiolabelled at one 3' end with 32P. Analysis of the radiolabelled DNA fragments produced in these experiments in DNA sequencing gels showed that the breaks occur at most but not all guanines and at some adenines.

Base Composition↗
PubMed1983

Tumorigenesis by transected cells in nude mice: a new method for detecting cellular transforming genes.

We have demonstrated that NIH 3T3 cells freshly transfected with either a cloned retroviral provirus or cell DNA derived from virally-transformed cells are able to induce tumors when injected subcutaneously into nude mice. Furthermore, cells transfected with DNA derived from at least three transformed human cell lines are able to induce tumors. These latter tumors contain human DNA sequences and DNA isolated from at least some of them is able to induce both foci and tumors in subsequent DNA transfection. Our data suggests that tumor induction by transfected 3T3 cells could serve as a powerful system for the selection of cells transformed by dominant cellular oncogenes. This method oviates the requirement that oncogenes induce clearly defined morphologically-transformed foci in order to be detected, and eliminates the need to maintain morphologically normal cells in tissue culture for many weeks, as well as the necessity of microscopically screning large numbers of tissue culture dishes. The tumors which arise in nude mice grow progressively, have been readily transplantable to other nude mice, and have been readily explantable into tissue culture. In addition, both DNA and RNA can be isolated directly from the mouse tumors to screen for the presence and expression of transfected sequences. We are currently examining other DNA samples from both human tumor-derived cell lines and primary human tumors to determine if this assay will detect and identify additional oncogenes. We are also studying the suitability of other normal cell lines as recipients in this assay, since cell lines which do not show readily discernible morphological transformation in monolayer culture may be suitable as tumor inducers following transfection. This assay should provide a convenient alternative method for detecting transforming genes and may help to increase the number of such sequence which can be identified and analyzed.

Animals↗
PubMed1982

New method for detecting cellular transforming genes.

Tumor induction in athymic nude mice can be used to detect dominant transforming genes in cellular DNA. Mouse NIH 3T3 cells freshly transfected with either cloned Moloney sarcoma proviral DNA or cellular DNA's derived from virally transformed cells induced tumors when injected into athymic nu/nu mice. Tumors were also induced by cells transfected with DNA from two tumor-derived and one chemically transformed human cell lines. The mouse tumors induced by human cell line DNA's contained human DNA sequences, and DNA derived from these tumors was capable of inducing both tumors and foci on subsequent transfection. Tumor induction in nude mice represents a useful new method for the detection and selection of cells transformed by cellular oncogenes.

Animals↗
PubMed1982

Inactivation of a diol epoxide by dihydrodiol dehydrogenase but not by two epoxide hydrolases.

The mutagenicity of r-8,t-9-dihydroxy-t-10, 11-oxy-8,9,10,11-tetrahydrobenz[a]anthracene (BA-8,9-diol 10, 11-oxide) toward Salmonella typhimurium TA 100 is not decreased by the presence of large amounts of highly purified microsomal or cytosolic epoxide hydrolase. However, highly purified dihydrodiol dehydrogenase inactivates this diol epoxide, which is a major DNA-binding metabolite of benz[a]anthracene. The K-region epoxide, benz[a]anthracene 5,6-oxide (BA 5,6-oxide) is efficiently inactivated by microsomal epoxide hydrolase, is much less readily inactivated by cytosolic epoxide hydrolase, and is not inactivated by dihydrodiol dehydrogenase. This inactivation of a diol epoxide by dihydrodiol dehydrogenase points to a new significance of this enzyme and a new level of control for diol epoxides.

Alcohol Oxidoreductases↗
PubMed1982

The metabolism and activation of polycyclic aromatic hydrocarbons in epithelial cell aggregates and fibroblasts prepared from rat mammary tissue.

The metabolism of 7,12-dimethylbenz[a]anthracene (DMBA), benzo[a]pyrene (BP) and benz[a]anthracene (BA) by epithelial cell aggregates and fibroblasts in culture has been investigated using mammary tissue obtained from female Wistar rats. The results show that: (a) both types of mammary cells metabolise all three hydrocarbons into ether- and water-soluble derivatives; (b) the patterns of metabolites produced by epithelial cells and fibroblasts are similar but that fibroblasts form more of the water-soluble materials; (c) the major dihydrodiols formed are the 8,9-dihydrodiols of BA and DMBA and the 7,8- and 9,10-dihydrodiols of BP; (d) all three hydrocarbons are metabolise to form products that bind covalently to protein but only the potent carcinogens BP and DMBA are metabolised to form derivatives that react covalently with DNA; and (e) the chromatographic profiles of the hydrocarbon-deoxyribonucleoside adducts formed in epithelial cells treated with either BP or DMBA are similar to those obtained in analogous experiment with fibroblasts.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1982

Molecular structure of (+/-)-7,8,9,10-tetrahydroxy-7,8,9,10-tetrahydrobenzo(a)pyrene determined by x-ray crystallography.

The molecular structure of a tetrahydrotetrol that is formed by hydrolysis of (+/-)-7 alpha, 8 beta-dihydroxy-9 beta, 10 beta-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene, has been determined by X-ray crystallographic methods. The relative orientations of the four hydroxyl groups of the racemic tetrahydrotetrol (7 alpha, 8 beta, 9 beta, 10 alpha) indicate that the tetrahydrotetrol was formed by the trans opening of the epoxide ring of the diol-oxide. The hydroxyl groups at positions 7 and 8 adopt a diequatorial conformation, while those at positions 9 and 10 adopt a diaxial conformation. Several other geometric features are discussed.

Benzopyrenes↗