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Biomedical subjects

C C Thompson

Publications and source records attributed to C C Thompson.

At least 55 records · Page 3Linked to original sources

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↗

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↗

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↗

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↗

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↗

Identification of a novel thyroid hormone receptor expressed in the mammalian central nervous system.

A complementary DNA clone derived from rat brain messenger RNA has been isolated on the basis of homology to the human thyroid hormone receptor gene. Expression of this complementary DNA produces a high-affinity binding protein for thyroid hormones. Sequence analysis and the mapping of this gene to a distinct human genetic locus indicate the existence of multiple human thyroid hormone receptors. Messenger RNA from this gene is expressed in a tissue-specific fashion with highest levels in the central nervous system.

Amino Acid Sequence↗

Sequence of the bacteriophage SP01 gene coding for transcription factor 1, a viral homologue of the bacterial type II DNA-binding proteins.

The Bacillus subtilis phage SP01, whose DNA contains 5-hydroxymethyluracil (hmUra) in place of thymine, codes for an abundant, small, basic protein called TF1. TF1 binds preferentially to hydroxymethyluracil-containing DNA and thereby selectively inhibits transcription of such DNA in vitro. The gene for TF1 has been sequenced. We find that this viral protein is a homologue of the ubiquitous bacterial type II DNA-binding proteins. The three-dimensional structure of one of these bacterial proteins has recently been determined. We are able to discern common as well as distinctive features in the amino acid sequence and the three-dimensional structure of the homologous viral protein.

Amino Acid Sequence↗

Purpuric oral and cutaneous lesions in a case of drug-induced thrombocytopenia.

This case, from all appearances, seems to constitute a case of secondary thrombocytopenia caused by drugs. Whether the etiology is one of over-dosage achieved when the two drugs, propranolol and disulfiram, were used in combination, or the interaction of the two drugs, or a response to disulfiram is difficult to state definitely. The use of propranolol alone does not seem to be the triggering factor because the patient resumed use of the drug without ill effect. Either an overdosage, exceeding a triggering threshold, was achieved in the combined usage of these two potentially purpuric drugs, or a reaction to disulfiram occurred subsequent to prior sensitizing exposure to this drug. The case does point out that the practitioner, whether dental or medical, should take a careful drug history--particularly in cases of purpura but also in other conditions, such as xerostomia, lichenoid reactions, and burning mouth or tongue. A copy of a current Physician's Desk Reference should be available in every dental or medical office.

Disulfiram↗

Oral manifestations of the congenital insensitivity-to-pain syndrome.

The congenital insensitivity-to-pain syndrome is a sensory syndrome in which pain is impaired. It has been variably classified under a variety of terms, on occasion leading to some confusion. The condition is present at birth. The patient is usually, but not always, normal with respect to intelligence, development, and psychological adjustments. Other sensory perceptions are normal. Traumatic lesions as a result of self-mutilative acts are not uncommon, especially at an early age. The condition may not be apparent clinically until the time of initial tooth eruption. As the primary teeth erupt, the patient acquires the necessary apparatus for self-infliction of wounds to oral structures, skin, and fingernails. A case of congenital indifference to pain is presented, with clinical documentation of tooth-related problems occurring over a 2-year period and of the steps taken to correct or minimize the traumatic effects of chewing.

Humans↗

Test-retest gains in WAIS scores after four retest intervals.

Administered the WAIS to 76 male college students on two occasions with a retest interval of either 1 week, 1 month, 2 months, or 4 months. Essentially all Verbal, Performance, and Full Scale IQs increased significantly on the retest. Increases in Verbal IQ for the four time intervals were 4.7, 1.8, 2.3, and .8 IQ points, respectively; the latter was the only nonsignificant gain found. The Performance IQ increased by 11.4, 9.8, 8.7, and 8.0 points for each subsequent time period, and the Full Scale IQ increased by 8.0, 5.7, 5.4, and 4.2 points for each respective time period. Test-retest correlations for the four intervals ranged from .91 to .72 for the Verbal IQ, .87 to .79 for the Performance IQ, and .94 to .74 for the Full Scale IQ. The results were pitted against similar test-retest studies, and clinical and research implications were discussed.

Humans↗

Molecular complexing ability of quinoline and its simple derivatives.

Electron donor-acceptor complexes for a group of quinolines and naphthalenes with 9-(dicyanomethylene)-2,4,7-trinitrofluorene in 1,2-dichloroethane were studied by optical absorption methods. Association constants, molar absorptivities, and charge-transfer transition energies were evaluated for each system, together with theoretically calcualted orbital energies and complex geometries. In contrast to the association constants and structures reported for N-heterocycle-halogen complexes, these studies indicate that, with a moderately large pi-electron acceptor, quinolines function as pi-rather then n-(lone-pair) donors. These results support intercalation models for drug-receptor interactions involving the quinoline moiety.

Chemical Phenomena↗