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Biomedical subjects

C D Reed

Publications and source records attributed to C D Reed.

At least 19 recordsLinked to original sources
PubMed1995

Health Promotion Schools of Excellence: a model program for Kentucky and the nation.

This article reviews the development and progress of an innovative, comprehensive school health project in the Jefferson County school district known as the Health Promotion Schools of Excellence (HPSE). This project features unique working relationships between public and private entities seeking a common goal: "A Healthier Community." The goals and development of HPSE have been formulated to coincide with the emerging directives of the Kentucky Education Reform Act (KERA) as well as the growing pressures to control health care costs through effective preventive measures. The results of testing following the first and second years of the project show an encouraging trend of improved physical fitness levels for all students (grades K-12) and improving levels of health knowledge and attitudes in elementary level children (grades 4-8) as well as school faculty and staff. These initial results, although encouraging, will only be meaningful if they translate over time into a healthier, more responsible cohort of adolescents and young adults when compared to their peers not involved in the project. The project, while only in its third year of development, has already been recognized at regional and national levels as a successful model of a comprehensive school health program. As the project continues and grows, the authors anticipate developing one of the nation's largest and most comprehensive longitudinal data bases of childhood and adolescent health information.

Adolescent↗
PubMed1992

GGT to GTT transversions in codon 12 of the K-ras oncogene in rat renal sarcomas induced with nickel subsulfide or nickel subsulfide/iron are consistent with oxidative damage to DNA.

Nickel is a toxic, mutagenic, and carcinogenic metal of significant occupational and environmental concern. Although several cellular targets of nickel have been identified, considerable evidence suggests that it can act indirectly upon DNA by inducing the formation of oxidized purines or pyrimidines that constitute promutagenic lesions. In this study, we examined nickel subsulfide (Ni3S2)- or Ni3S2/iron-induced renal sarcomas in F344 rats for the presence of transforming mutations in the K-ras oncogene. Selective oligonucleotide hybridization analysis of K-ras gene sequences amplified by polymerase chain reaction revealed that 1 of 12 primary tumors induced with Ni3S2 and 7 of 9 primary tumors induced with Ni3S2/iron contained exclusively GGT to GTT activating mutations in codon 12. These mutations are consistent with the known ability of nickel, in the presence of an oxidizing agent, to catalyze formation of 8-hydroxydeoxyguanosine, which in turn promotes misincorporation of dATP opposite the oxidized guanine residue. The presence of GGT to GTT transversions was confirmed by direct sequencing of the polymerase chain reaction products. Sequencing also revealed that there were no transforming mutations in codons 13 or 59-61. Additionally, a direct correlation between shortened tumor latency and the presence of activating ras mutations was noted. These results show that, in rat kidney, Ni3S2 can induce transforming mutations that are consistent with the ability of nickel to produce oxidative lesions and that iron, which exacerbates the extent of cellular oxidative damage, can enhance the frequency of these transforming mutations.

Animals↗
PubMed1989

Infrequent activation of K-ras, H-ras, and other oncogenes in hepatocellular neoplasms initiated by methyl(acetoxymethyl)nitrosamine, a methylating agent, and promoted by phenobarbital in F344 rats.

Fischer 344/Ncr rats of both sexes were subjected to partial hepatectomy and then initiated 21-24 h later by a single injection of methyl(acetoxymethyl)nitrosamine at 0.1 mmol/kg body weight via the portal vein. Beginning 3 weeks later, development of hepatocellular neoplasms in initiated rats was promoted by feeding 0.05% phenobarbital (PB) in the diet. Not only intrahepatic lesions but also a variety of extrahepatic tumors were induced. High-molecular-weight DNAs were prepared from 67 samples of grossly normal liver containing multiple preneoplastic foci/areas of microscopic dimensions, 137 hepatocellular adenomas (nodules), 93 hepatocellular carcinomas (HCC), 10 cholangiomas, and 25 extrahepatic tumors in 95 rats and tested for transforming activity in the NIH 3T3 transfection assay. DNA preparations from 7 of 93 HCCs, 2 of 10 cholangiomas, 2 of 137 nodules, 1 histiocytic sarcoma, and 1 thyroid carcinoma were positive in the transfection assay. Southern blot analysis showed that NIH 3T3 transformants induced by DNA from 5 HCCs, 1 hepatocellular adenoma, 1 cholangioma, 1 histiocytic sarcoma, and 1 thyroid carcinoma contained an activated K-ras gene of rat origin. Rat-derived H-ras was identified in transformants from 2 additional HCCs and rat c-raf from 1 hepatocellular adenoma. The transforming gene from one cholangioma showed no sequence homology to the ras genes, neu, or c-raf. Immunoprecipitation analysis of ras Mr 21,000 protein in 11 transformants indicated that, based upon protein electrophoretic mobilities, activation of the ras genes consistently resulted from mutations in codon 12 of these genes. Selective oligonucleotide analysis revealed that a G----A transition in the second base of codon 12 of K-ras was present in the 9 K-ras-positive transformants and also in DNAs prepared from the original tumors. In contrast, oligonucleotide hybridization experiments with DNAs from 35 hepatocellular tumors that were negative in transfection assays revealed the presence of mutant K-ras in 1 of 15 HCCs; no mutation could be detected in 20 transfection-negative adenomas. The infrequency of detection of a specific oncogene, more frequent detection of oncogenes in malignant tumors, and failure to observe activated oncogenes in preneoplastic lesions suggest that activation of ras oncogenes may occur as a late and infrequent event in the evolution of some rat hepatocellular neoplasms and that mutation of a specific ras locus is not an obligatory early event in the genesis of these neoplasms.

Animals↗
PubMed1989

N-nitrosocimetidine as an initiator of murine skin tumors with associated H-ras oncogene activation.

N-Nitrosocimetidine (NCM) is a derivative of the drug cimetidine, a methylguanidine derivative used in the treatment of peptic ulcer, and is known to be inactive as a complete mouse skin carcinogen, even when given in repeated high doses for a long period. In the current experiment, NCM was tested for its ability to initiate skin tumors on Sencar mice. It was applied at doses of 1 or 0.3 mg, 5 times/week for 6 weeks, followed by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA), 1 microgram, 2 times/week for 50 weeks. Controls received acetone. The higher NCM dose had significant effects on TPA-promotable tumors, resulting in shortened time to first tumor, increased incidence of all tumors (2-fold) and of malignant tumors (4-fold), and greater tumor growth rate (2-fold), compared with the acetone/TPA-treated mice. The mice given the lower NCM dose did not exhibit increased tumor incidence, but their tumors had a significantly higher growth rate (3-fold) than those of the TPA controls. NCM without TPA treatment caused no tumors. Thus, NCM is a definitive, though weak initiator of TPA-promotable tumors. Nine tumors from the NCM-treatment groups were analyzed for activated oncogenes by the NIH 3T3 cell transfection assay. Five were positive and four of these were found by selective oligonucleotide hybridization analysis to have an A to T transversion in the second position of codon 61 of the H-ras oncogene. One of two tumors from the acetone/TPA group also contained transforming DNA and demonstrated this mutation. None of the tumors had a G----A transition mutation at the second position of codon 12 of this oncogene. Tumor initiation by NCM may then be associated with the same oncogene mutation reported for mouse skin tumors initiated by other types of carcinogens, although occurrence of the mutated oncogene in TPA controls precludes a definitive conclusion.

Animals↗
PubMed1987

Activated neu oncogene sequences in primary tumors of the peripheral nervous system induced in rats by transplacental exposure to ethylnitrosourea.

Neurogenic tumors were selectively induced in high incidence in F344 rats by a single transplacental exposure to the direct-acting alkylating agent N-ethyl-N-nitrosourea (EtNU). We prepared DNA for transfection of NIH 3T3 cells from primary glial tumors of the brain and from schwannomas of the cranial and spinal nerves that developed in the transplacentally exposed offspring between 20 and 40 weeks after birth. DNA preparations from 6 of 13 schwannomas, but not from normal liver, kidney, or intestine of tumor-bearing rats, transformed NIH 3T3 cells. NIH 3T3 clones transformed by schwannoma DNA contained rat repetitive DNA sequences, and all isolates contained rat neu oncogene sequences. One schwannoma yielded a transformant with rat-specific sequences for both neu and N-ras. A point mutation in the transmembrane region of the putative protein product of neu was identified in all six transformants and in the primary tumors from which they were derived as well as in 5 of 6 schwannomas tested that did not transform NIH 3T3 cells. Of 59 gliomas, only one yielded transforming DNA, and an activated N-ras oncogene was identified. The normal cellular neu sequence for the transmembrane region, but not the mutated sequence, was identified in DNA from all 11 gliomas surveyed by oligonucleotide hybridization. Activation of the neu oncogene, originally identified [Schechter, A.L., Stern, D.F., Vaidyanathan, L., Decker, S.J., Drebin, J.A., Greene, M.I. & Weinberg, R.A. (1984) Nature (London) 312, 513-516] in cultured cell lines derived from EtNU-induced neurogenic tumors that by biochemical but not histologic criteria were thought to originate in the central nervous system in BD-IX rats, appears specifically associated with tumors of the peripheral nervous system in the F344 inbred strain.

Animals↗
PubMed1985

Selective growth in culture of fetal rat renal collecting duct anlagen. Morphologic and biochemical characterization.

Cell culture conditions were devised that selectively supported growth of 13 or 14 gestation day F344 rat ureteric bud, the renal collecting duct anlagen. These same conditions also inhibited the growth of metanephrogenic mesenchyme, precursor of structures proximal to the duct. Isolated buds were cultured in Ham's F12 medium supplemented with epidermal growth factor, selenium, insulin, hydrocortisone, prostaglandin E1, transferrin, and triiodothyronine; fetal bovine serum (1%) was required for continuous propagation. Cultured cells were epithelial in morphology and formed domes. By electron microscopy, many structural characteristics of highly differentiated cells were evident: numerous mitochondria, Golgi apparatus, extensive endoplasmic reticulum, an occasional cilium, intracytoplasmic filaments, polarized formation of microvilli, and gap junctions. Histochemistry revealed considerable functional differentiation as well. Cultured bud cells, adult collecting duct, and fetal duct anlagen were positive for acid phosphatase, membrane-localized ATPase, and nonspecific esterase. Bud cells and fetal duct anlagen expressed high levels of gamma-glutamyl transpeptidase activity while adult collecting duct exhibited slight activity. In addition, immunocytochemical observation of intermediate filament expression revealed the presence of epithelial cytokeratins but absence of mesenchymal vimentin in cultured bud cells and fetal and adult collecting ducts. These results indicate that the culture conditions described can maintain the partially differentiated fetal collecting duct anlagen in a state consistent with its embryonal derivation, and therefore may be useful in culture studies of renal differentiation.

Acid Phosphatase↗
PubMed1982

A rapid bioassay to monitor murine leukemia virus infection in mice using cellular gp 71 binding.

A rapid and sensitive bioassay based on the availability of cell surface receptors for the binding of purified envelope glycoprotein, gp71, of Rauscher murine leukemia virus (R-MuLV) was developed to serially monitor viral-induced leukemogenesis in individual BALB/cAnN mice. The specificity of the bioassay was demonstrated by the competition of [125I]gp71 cellular binding with murine ecotropic viruses, purified unlabelled R-MuLV envelope glycoprotein and by antiserum to R-MuLV gp71. In contrast, there was no effect on the [125I]gp71 binding level with the addition of murine xenotropic viruses, R-MuLV p30, or several other proteins. The [125I]gp71 binding level of circulating leukocytes was significantly (P less than 0.05) reduced in mice after R-MuLV infection. The reduction of cellular gp71 binding developed in two stages and the latter stage was highly dependent (P less than 0.05) on circulating infectious virus titer. Using this technique, the gp71 cellular binding levels of 48-60 individual mice can be assayed in a 4 h period. The advantages of this bioassay compared to standard immunological and tissue culture techniques used in studying retrovirus expression and viral-cell interactions are discussed.

Animals↗
PubMed1980

Identification of an interferon in murine placentas.

It is becoming increasingly apparent that interferon exerts a major role in cellular regulatory processes. Besides its well known antiviral properties, interferon has been shown to affect cell surface antigen expression, lymphoid cell function, as well as cellular protein synthesis and growth. To date, however, there is little information available on the mechanism of interferon production in vivo except in response to a variety of exogenously administered viral and nonviral systemic inducers. We report here the detection of a pregnancy-associated elevation of interferon, or an interferon-like component, in selected reproductive tissues of mice.

Animals↗
PubMed1979

Depression of Rauscher leukemia virus envelope glycoprotein gp71 binding by lymphoid cells during leukemogenesis in mice.

The availability of membrane receptors for the 71,000-dalton envelope glycoprotein (gp71) of Rauscher murine leukemia virus on splenic and thymic cells from BALB/c mice during Rauscher murine leukemia virus-induced leukemogenesis was determined utilizing a radiolabeled gp71 binding assay. Shortly after infection, the relative cellular [125I]gp71 binding level decreased, first with splenic cells (at day 7 to 10 after infection) and later with thymic cells (at day 10 to 20 after infection). The dependency of the reduction of binding on the replication of the inoculated virus was demonstrated by regression analyses using cellular gp71 binding level as the dependent variable and infectious virus titer, as well as viral gp71 and p30 levels, of spleens and thymuses from infected mice as independent variables. With each independent variable, the reduction of gp71 binding for both cell types was highly dependent (P less than 0.01) on the level of virus detected in their respective organ. In the early stages of leukemogenesis, the [125I]gp71 binding level declined to approximately 20 to 30% of control values. During this period the rate of reduction of binding was very rapid and, in general was similar for both splenic and thymic cells. Further progression of the disease resulted in little or no further reduction in binding. The application of this technique to monitor host ecotropic virus synthesis and to study cell surface virus receptor control mechanisms in vivo is discussed.

Animals↗
PubMed1977

Binding characteristics of Rauscher leukemia virus envelope glycoprotein gp71 to murine lymphoid cells.

The major envelope glycoprotein (gp71) purified from Rauscher leukemia virus (R-MuLV) binds efficiently to murine lymphoid cells but not to either murine nonlymphoid cells or lymphoid cells from other species. Binding of 125I-labeled R-MuLV gp71 was competitively inhibited by unlabeled glycoprotein, as well as by whole R-MuLV, but not by murine xenotropic viruses, R-MuLV p30, and several unrelated proteins. Polyacrylamide gel electrophoresis profiles of iodinated gp71 after binding to lymphoid cells were similar to prebound profiles. Antibody to R-MuLV gp71 prevented binding, whereas normal serum had no effect. Adsorption of the glycoprotein to murine lymphoid cells occurs rapidly and is time and temperature dependent. The procedure described is sensitive for detecting the binding activity of approximately 10(4) cells. Binding was proportional up to 2.5 X 10(5) cells per ml and plateaued above 10(7) cells per ml. In the presence of excess R-MuLV gp71, BALB/c thymocytes bound approximately 2.4 X 10(4) molecules per cell.

Animals↗
PubMed1977

Inhibition of lymphocyte transformation by disrupted murine oncornavirus.

Freeze-thaw preparations of banded Rauscher murine leukemia virus markedly suppressed the in vitro cellular-mediated blastogenic response of murine splenic lymphocytes to phytohemagglutinin-P and to allogeneic cells in two-way mixed-leukocyte reaction. Suppression was shown not to be due to cytotoxicity or to virus-mitogen binding. It is suggested that a virion envelope component interferes with cellular-mediated immunity by altering cell recognition sites.

Animals↗
PubMed1972

Activation of C-type RNA virus markers in mouse uterine tissue.

Synthetic estrogenic compounds, both steroidal and nonsteroidal, and radiation activate markers of C-type virus information in mouse uterine tissue. Both the group-specific viral antigen and the RNA-directed DNA polymerase can be detected within 4 days after stimulation. These observations strengthen the concept of host-modified control mechanisms for expression of C-type virus markers.

Animals↗