Search PubMed⌕ Search

Biomedical subjects

C C Thompson

Publications and source records attributed to C C Thompson.

At least 19 recordsLinked to original sources
PubMed1998

Late G1 accumulation after 2 Gy of gamma-irradiation is related to endogenous Raf-1 protein expression and intrinsic radiosensitivity in human cells.

We have previously reported a correlation between high endogenous expression of the protein product of the RAF-1 proto-oncogene, intrinsic cellular radiosensitivity and rapid exit from a G2/M delay induced by 2 Gy of gamma-irradiation. Raf1 is a positive serine/threonine kinase signal transduction factor that relays signals from the cell membrane to the MAP kinase system further downstream and is believed to be involved in an ionizing radiation signal transduction pathway modulating the G1/S checkpoint. We therefore extended our flow cytometric studies to investigate relationships between radiosensitivity, endogenous expression of the Raf1 protein and perturbation of cell cycle checkpoints, leading to alterations in the G1, S and G2/M populations after 2 Gy of gamma-irradiation. Differences in intrinsic radiosensitivity after modulation of the G1/S checkpoint have generally been understood to involve p53 function up to the present time. A role for dominant oncogenes in control of G1/S transit in radiation-treated cells has not been identified previously. Here, we show in 12 human in vitro cancer cell lines that late G1 accumulation after 2 Gy of radiation is related to both Raf1 expression (r = 0.91, P = 0.0001) and the radiosensitivity parameter SF2 (r = -0.71, P = 0.009).

Blotting, Western↗
PubMed1997

The product of a thyroid hormone-responsive gene interacts with thyroid hormone receptors.

Thyroid hormone is a critical mediator of central nervous system (CNS) development, acting through nuclear receptors to modulate the expression of specific genes. Transcription of the rat hairless (hr) gene is highly up-regulated by thyroid hormone in the developing CNS; we show here that hr is directly induced by thyroid hormone. By identifying proteins that interact with the hr gene product (Hr), we find that Hr interacts directly and specifically with thyroid hormone receptor (TR)-the same protein that regulates its expression. Unlike previously described receptor-interacting factors, Hr associates with TR and not with retinoic acid receptors (RAR, RXR). Hr can act as a transcriptional repressor, suggesting that its interaction with TR is part of a novel autoregulatory mechanism.

Animals↗
PubMed1996

Thyroid hormone-responsive genes in developing cerebellum include a novel synaptotagmin and a hairless homolog.

Proper development of the mammalian CNS requires sufficient thyroid hormone; thyroid hormone deficiency during a brief perinatal period produces severe neurological defects in humans and experimental animals. Thyroid hormone exerts its effects through nuclear receptors, which modulate the transcription of downstream genes in response to hormone binding. Surprisingly, few genes that are regulated by thyroid hormone receptors in the CNS have been described. Here, I report the isolation and characterization of genes that are expressed in response to thyroid hormone in developing rat brain. One such gene (Srg1) encodes a novel protein related to synaptotagmin, a protein involved in regulating neurotransmitter release; another (hr) encodes a putative zinc finger protein related to the product of a recently identified mouse gene, hairless. Both Srg1 and hr are induced rapidly (<4 hr), suggesting that they are regulated directly by thyroid hormone. The temporal and spatial expression of both Srg1 and hr is characteristic of genes important to nervous system development. Srg1 and hr are likely part of a cascade of gene activation induced by thyroid hormone that is critical for CNS organization and development.

Aging↗
PubMed1996

Exit from G2 phase after 2 Gy gamma irradiation is faster in radiosensitive human cells with high expression of the RAF1 proto-oncogene.

We have previously noted that high endogenous expression of the protein product of the full-length RAF1 proto-oncogene is related to relative intrinsic cellular radiosensitivity in 19 human cells lines in vitro. This appeared to be unrelated to the parameters of cell kinetics. In rodent and human cell lines transfected with dominant oncogenes, including Myc and MYC, Hras and HRAS and SV40, increased radioresistance has been accompanied by increased delay in progress through the G2 phase of the cell cycle after irradiation. We have thus examined the putative relationship between RAF1 expression and postirradiation perturbation of G2 phase in six of the human cell lines for which data have been reported previously. These lines exhibit a wide range of both radiosensitivity and Raf1 protein levels as measured previously by Western blotting. We report here that the cell lines whose cells appear to exit more rapidly from G2 phase are more radiosensitive (r = 0.91, P = 0.01) and express high levels of Raf1 protein (r = -0.93, P = 0.006).

Cell Line↗
PubMed1995

Accidental contamination from uranium compounds through contact with ceramic dinnerware.

Examination of orange-colored dinnerware samples purchased in antique stores and flea markets has revealed the occasional presence of surface uranium compounds that are readily transferred to the hands and clothing. We have further been able to produce soluble uranium compounds on the surfaces of clean dishes by exposing them to household vinegar or bleach. We estimate that handling of a contaminated dish can transfer up to 1-2 becquerels or more of uranium compounds to the hands. Uranium contamination is of concern because the element is not only an alpha emitter but also a chemical nephrotoxin. Although the amount of uranium likely to be ingested as a result of casual handling may be small, it could still exceed by several times the amount occurring in the average diet (about 40 mBq/day). Furthermore, since fresh surface compounds are readily formed, it is possible that a person who regularly handles or eats from uranium-glazed dinnerware can accidentally ingest significant amounts of uranium.

Ceramics↗
PubMed1993

Superoxide scavengers do not prevent ischemia-induced alteration of cerebral vasodilation in piglets.

Piglet brains generate superoxide during postischemic reperfusion, and topical application of activated oxygen species alters pial arteriolar responses. We investigated effects of pretreatment with scavengers of superoxide and H2O2 on ischemia-induced alterations of pial arteriolar responses in anesthetized newborn pigs. Four groups were studied: 1) time control, 2) untreated ischemia, 3) ischemia pretreated topically and systemically (conjugated to polyethylene glycol) with superoxide dismutase (SOD) and catalase, and 4) ischemia pretreated with Tiron. Pretreatment with SOD conjugated to polyethylene glycol alone during postischemic reperfusion effectively removed superoxide from its site of generation during postischemic reperfusion, but topical SOD was used also an insurance. Piglets were studied before and after 20 min of total cerebral ischemia caused by maintaining intracranial pressure above mean arterial pressure. As reported previously, before ischemia, hypercapnia and isoproterenol dilated pial arteries and arterioles and hypercapnia but not isoproterenol increased cortical periarachnoid cerebrospinal fluid 6-keto-prostaglandin F1 alpha, measured as an index of cerebral cortical prostacyclin synthesis. After cerebral ischemia, pial arterioles did not dilate in response to hypercapnia and 6-keto-prostaglandin F1 alpha did not increase, but dilation to isoproterenol was unchanged. The present study found that treatment with SOD/catalase or Tiron did not prevent loss of vasodilation to hypercapnia or the loss of hypercapnia-induced cerebral 6-keto-prostaglandin F1 alpha synthesis after cerebral ischemia. The postischemic loss of cerebral vasodilation to hypercapnia does not appear to involve superoxide or a subsequent reduced form of oxygen.

6-Ketoprostaglandin F1 alpha↗
PubMed1992

Postoperative pulmonary toxicity associated with mitomycin-C therapy.

As more patients survive cancer, and as more sophisticated multidrug antineoplastic protocols are developed, the chances of an anesthesiologist's coming into contact with patients who have been treated with such protocols are increasing. The anesthesiologist who must administer anesthesia to a patient who has had chemotherapy must be cognizant of the particular antineoplastic agents that have the potential for producing occult pulmonary dysfunction. Anesthetic management of these cases must be carefully planned and titrated to prevent further lung injury.

Adult↗
PubMed1991

Convergence of Ets- and notch-related structural motifs in a heteromeric DNA binding complex.

Analysis of the heteromeric DNA binding protein GABP has revealed the interaction of two distinct peptide sequence motifs normally associated with proteins located in different cellular compartments. The alpha subunit of GABP contains an 85-amino acid segment related to the Ets family of DNA binding proteins. The ETS domain of GABP alpha facilitates weak binding to DNA and, together with an adjacent segment of 37 amino acids, mediates stable interaction with GABP beta. The beta subunit of GABP contains four imperfect repeats of a sequence present in several transmembrane proteins including the product of the Notch gene of Drosophila melanogaster. These amino-terminal repeats of GABP beta mediate stable interaction with GABP alpha and, when complexed with GABP alpha, directly contact DNA. These observations provide evidence for a distinct biochemical role for the 33-amino acid repeats, and suggest that they may serve as a module for the generation of specific dimerization interfaces.

Animals↗
PubMed1991

Identification of Ets- and notch-related subunits in GA binding protein.

Recombinant cDNA clones that encode two distinct subunits of the transcription factor GA binding protein (GABP) have been isolated. The predicted amino acid sequence of one subunit, GABP alpha, exhibits similarity to the sequence of the product of the ets-1 protooncogene in a region known to encompass the Ets DNA binding domain. The sequence of the second subunit, GABP beta, contains four 33-amino acid repeats located close to the NH2-terminus of the subunit. The sequences of these repeats are similar to repeats in several transmembrane proteins, including Notch from Drosophila melanogaster and Glp-1 and Lin-12 from Caenorhabditis elegans. Avid, sequence-specific binding to DNA required the presence of both polypeptides, revealing a conceptual convergence of nuclear transforming proteins and membrane-anchored proteins implicated in developmentally regulated signal transduction processes.

Amino Acid Sequence↗
PubMed1991

Direct repeats as selective response elements for the thyroid hormone, retinoic acid, and vitamin D3 receptors.

We report here the identification of thyroid hormone response elements (TREs) that consist of a direct repeat, not a palindrome, of the half-sites. Unlike palindromic TREs, direct repeat TREs do not confer a retinoic acid response. The tandem TRE can be converted into a retinoic acid response element by increasing the spacing between the half-sites by 1 nucleotide, and the resulting retinoic acid response element is no longer a TRE. Decreasing the half-site spacing by 1 nucleotide converts the TRE to a vitamin D3 response element, while eliminating response to T3. These results correlate well with DNA-binding affinities of the thyroid hormone, retinoic acid, and vitamin D3 receptors. This study points to the general importance of tandem repeat hormone response elements and suggests a simple physiologic code exists in which half-site spacing plays a critical role in achieving selective hormonal response.

Animals↗
PubMed1991

Nucleotide pools and mutagenic effects of alkylating agents in wild-type and APRT-deficient Friend erythroleukaemia cells.

Wild-type Friend mouse erythroleukaemia cells (clone 707) were compared with adenine phosphoribosyltransferase (APRT)-deficient mutant subclones (707DAP8 and 707DAP10) for sensitivity to cell killing and mutagenesis by ethyl methanesulphonate (EMS) and methyl methanesulphonate (MMS). Cells were exposed to 0-300 micrograms/ml EMS and to 0-20 micrograms/ml MMS for a period of 16 h. A slight difference was found between wild-type cells and the two APRT-deficient subclones in terms of sensitivity to cell killing by both mutagens. The APRT-deficient subclones were, however, significantly more sensitive than wild-type cells to mutagenesis to 5-bromo-2-deoxyuridine resistance and 6-thioguanine resistance by EMS and MMS. The APRT-deficient subclones were found to have significantly decreased levels of dATP and dTTP nucleotides and decreased levels of all four ribonucleoside triphosphates (ATP, GTP, CTP and UTP) relative to wild-type cells. Wild-type Friend cells were found to have insignificant levels O6-methylguanine-DNA methyl transferase and it is suggested that the increased mutagen sensitivity of APRT-deficient cells may be due to imbalance of deoxyribonucleoside triphosphate pools during DNA excision-repair processes, or more probably due to deficiency of ATP for ATP-dependent DNA excision-repair enzymes.

Alkylating Agents↗
PubMed1989

Protein encoded by v-erbA functions as a thyroid-hormone receptor antagonist.

The thyroid-hormone receptor can, in the absence of its ligand, suppress activity of a responsive promoter. Addition of thyroid hormone, however, results in the stimulation of expression. The oncogenic derivative of the thyroid-hormone receptor, v-erbA, acts as a constitutive repressor and, when coexpressed with the receptor, blocks activation by thyroid hormone. Thus, v-erbA may be the first example of a dominant negative oncogene.

Animals↗
PubMed1989

Positional effect of cis/trans alpha globin gene deletions on the formation of "H" bodies.

Normal individuals have four alpha-globin genes, two on each member of the chromosome 16 pair (alpha alpha/alpha alpha). The alpha-thalassemia trait phenotype associated with deletions of two alpha-genes can be either on the same chromosome, the cis type (alpha alpha/--), or on opposite chromosomes, the trans type (alpha-/alpha-). Traditionally, the observation on vitally stained smears of occasional cells containing "H" bodies has been used as an important diagnostic criterion for alpha-thalassemia trait. These "H" bodies are thought to be precipitated beta tetramers because of the presence of excess beta-globin chains. Our study in patients with various alpha-genotypes indicates that normal subjects (alpha alpha/alpha alpha) and patients with silent alpha-thalassemia trait (alpha alpha/alpha-) generally have no "H" bodies. However, patients with the two-gene deletion of the cis type alpha-thalassemia (alpha alpha/--) show the occasional "H" body, and those with Hb "H" disease (alpha-/-- or alpha cs-/--) show many such bodies. On the other hand, patients with two-gene deletion of the trans type (alpha-/alpha-) do not show "H" bodies. The number of "H" bodies found does not appear to correlate directly with the degree of imbalance in alpha- and beta-chain production among the various alpha-genotypes examined. The chemical nature of "H" bodies is discussed, and an alternative hypothesis that embryonic zeta chains expressed in the cis type but not in the trans type of alpha-thalassemia are involved in the formation of "H" bodies is proposed.

Blotting, Southern↗
PubMed1989

Two kinetic methods to study the regulation of mammalian hexokinases.

Two new kinetic analyses for mammalian hexokinases are presented, which permit one to study the regulation of these enzymes by product inhibition. One method uses the pyruvate kinase-coupled assay and the other the glucose-6-phosphate dehydrogenase-coupled assay. Both methods give simple linear plots, which indicate that the magnesium-ATP complex overcomes the glucose 6-phosphate inhibition competitively, but by atypical kinetics. A new regulation coefficient (Kr) was defined and it was shown that, with both assay methods, the reciprocals of the slopes of the simple linear plots are proportional to Kr.[Mg.ATP].NADP, but not NAD, was found to be a powerful inhibitor of pig heart hexokinase.

Animals↗
PubMed1989

Trans-activation by thyroid hormone receptors: functional parallels with steroid hormone receptors.

The effects of thyroid hormones are mediated through nuclear receptor proteins that modulate the transcription of specific genes in target cells. We previously isolated cDNAs encoding two different mammalian thyroid hormone receptors, one from human placenta (hTR beta) and the other from rat brain (rTR alpha), and showed that their in vitro translation products bind thyroid hormones with the characteritistic affinities of the native thyroid hormone receptor. We now demonstrate that both of the cloned receptors activate transcription from a thyroid hormone-responsive promoter in a hormone-dependent manner, with rTR alpha eliciting a greater response than hTR beta. The putative functional domains of the thyroid hormone receptors were examined by creating chimeric thyroid hormone/glucocorticoid receptors, producing receptors with hybrid functional properties. These experiments support the proposal that the thyroid hormone receptors are composed of interchangeable functional domains, and indicate that the mechanism of hormone-inducible gene regulation has been conserved in steroid and thyroid hormone receptors.

Animals↗
PubMed1989

The interaction of anti 3.7 type quadruplicated alpha-globin genes and heterozygous beta-thalassemia.

Human alpha-globin gene mapping was carried out using a variety of restriction endonucleases (Bgl II, Bam HI, Hind III, Eco RI, Hpa I, Pvu II and Rsa I) on members of a family from El Salvador and a female from Hawaii, of Chinese descent, whose hematological and clinical parameters were those of beta-thalassemia intermedia. Southern blot DNA analysis showed that the beta-thalassemia intermedia patients from the above two families had the same anti 3.7 type quadruplicated alpha-genes on the one chromosome, and that they had the alpha genotype alpha 2, alpha 1 alpha 2, alpha 1 alpha 2, alpha 1/alpha 2, alpha 1. The alpha/beta globin synthesis ratios of the three affected Salvadoran patients were around 2.5, and the affected Hawaiian patient was 2.9. These ratios strongly suggest that the additional alpha-genes in the anti 3.7 type rearrangement are biologically active, thus accounting for the severity of the heterozygous beta-thalassemia observed among these patients.

DNA↗