Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0004135 (ATM)
 13,001 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Binding sites for angiotensin II were found, in a line of Swiss 3T3 cells (designated as R3T3 cells), that were insensitive to Dup 753 and dithiothreitol yet were sensitive to PD 123319, making them members of the AT2 class of angiotensin II binding sites. These binding sites appeared not to be coupled to guanine nucleotide-binding proteins, and affinity labeling experiments revealed a specifically labeled protein with an apparent molecular weight of about 100,000. Treatment of cells with angiotensin II revealed no perturbation of common signaling pathways, including stimulation of phosphatidylinositol turnover, effects on levels of cAMP, tyrosine kinase activity, and release of arachidonic acid. Also, angiotensin II or PD 123319 had no effect on cell growth, mitogenesis, or hypertrophy or on mitogenesis or hypertrophy stimulated by several growth factors. These results show that the AT2 binding site is quite distinct from the AT1 site in terms of molecular weight, binding properties, and coupling to second messenger systems. Although the significance of this novel angiotensin II binding site remains obscure, the identification of cell lines selectively expressing it should greatly aid in the understanding of its regulation and function.
Mol Pharmacol 1991 Sep
PMID:Characterization of angiotensin II (AT2) binding sites in R3T3 cells. 189 25

Quantitative autoradiography was used to characterize angiotensin AT1 and AT2 receptors, in the rat aorta at three developmental ages; embryonic day 18 (E18), and postnatal weeks 2 and 8. The expression of angiotensin receptors was higher in the aorta of E18 and 2-week-old rat. A major proportion of the angiotensin receptors expressed in the aorta at these two ages was AT2 (84 and 81% respectively). Conversely, in the aorta of 8-week-old rats, AT1 was the predominant angiotensin receptor subtype (71%). In 8-week-old rats, the AT2 subtype was also present (28%). In pre- and postnatal rats, [125I]Sar1-angiotensin II binding to AT1 receptors was sensitive to GTP gamma S whereas binding to AT2 receptors was not. AT2 receptors may serve an important role during stages of rapid growth of the aorta, and also have a significant function in the adult vasculature.
Biochem Biophys Res Commun 1991 Sep 30
PMID:Changes in expression of angiotensin receptor subtypes in the rat aorta during development. 193 Jan 81

Electrophysiological examinations were performed on 32 children aged three to 17 years who had typical clinical manifestations of ataxia-telangiectasia (AT). EMG findings demonstrated neurogenic lesions, more pronounced in the distal leg muscles of older children where they resembled the picture characteristic of motor neuron disease. Electrophysiological and nerve conduction results showed that generalised, progressive, sensory nervous system degeneration, with neurogenic amyotrophy affecting the distal part of the lower limbs, is an established feature of this disease and can be considered one of the diagnostic characteristics of AT. This allows the syndrome to be classified as an hereditary spinocerebellar degeneration.
Dev Med Child Neurol 1990 Sep
PMID:Progressive peripheral neuron degeneration in ataxia-telangiectasia: an electrophysiological study in children. 217 59

Ataxia-telangiectasia and xeroderma pigmentosum are human hereditary diseases in which patients are cancer prone and demonstrate increased sensitivity to DNA damage by ionizing and ultraviolet radiation, respectively. In culture, both ataxia-telangiectasia and xeroderma pigmentosum skin fibroblasts show increased synthesis and secretion of the extracellular matrix proteins fibronectin and collagen. To determine whether these differences in protein production result from fundamental abnormalities in regulation of genes associated with cellular interactions, we compared the effects of trifluoperazine and 12-O-tetradecanoylphorbol-13-acetate on expression of the extracellular matrix-degrading metalloproteinases, procollagenase and prostromelysin, by normal, ataxia-telangiectasia, and xeroderma pigmentosum fibroblasts. After trifluoperazine treatment the overall levels of these metalloproteinases were much greater in three ataxia-telangiectasia cell strains and in cells from xeroderma pigmentosum complementation groups A and D than in normal cells. In contrast, cells from xeroderma pigmentosum complementation group C produced only slightly more procollagenase than normal cells. 12-O-tetradecanoylphorbol-13-acetate also induced higher than normal levels of procollagenase in some ataxia-telangiectasia and xeroderma pigmentosum strains, but less than that induced by trifluoperazine. Because increased extracellular accumulation of matrix-degrading enzymes has long been implicated in metastatic progression, this altered expression of procollagenase and prostromelysin in ataxia-telangiectasia and xeroderma pigmentosum cells could play an important role in the pathogenesis of various tumors in individuals with these genetic diseases.
In Vitro Cell Dev Biol 1990 Sep
PMID:Enhanced expression of procollagenase in ataxia-telangiectasia and xeroderma pigmentosum fibroblasts. 217 6

Aware of having tackled a difficult topic in the present paper and also of the fact that all gnathological philosophies are open to sundry criticisms, we believe we have made a valid contribution with experimental, clinical and practical consequences in the functional reconstruction of the incisor guide. In addition, the clinical experimentation undertaken, even with the limitations resulting from the small number of patients examined, will allow us to study the group of patients at risk for the appearance of ATM pathologies over a period of twelve years.
Dent Cadmos 1990 Sep 15
PMID:[Fixed prosthetic reconstruction. Restoration of upper incisors. 3]. 224 71

A technique for nonradioactive in situ hybridization on human metaphase chromosomes has been developed to localize human cosmid clones. The simple procedure using two fluorescent dyes (fluorescein and propidium iodide) allows the simultaneous identification of chromosomal R-bands and hybridization signal in a single screening of the slides. This technique has been used for rapid correlation of the genetic and physical map of chromosome 11q13-qter in the region of genes responsible for ataxia-telangiectasia and tuberous sclerosis.
Proc Natl Acad Sci U S A 1990 Sep
PMID:Simultaneous localization of cosmids and chromosome R-banding by fluorescence microscopy: application to regional mapping of human chromosome 11. 239 67

Recent reports from a number of laboratories have linked radiosensitivity in ataxia telangiectasia (A-T) to a large and prolonged block of some cells in G2 phase. Previous results from this laboratory, largely with one Epstein-Barr virus-transformed A-T lymphoblastoid cell line, presented evidence for a dramatic increase in the number of cells in G2 phase over controls during a 24-h period post irradiation. We describe here a study of the effect of gamma-radiation on G2 phase delay in several A-T cell lines. Based on previous results with several cell lines 24 h post irradiation was selected as the optimum time to discriminate between G2 phase delay in control and A-T cells. All A-T homozygotes showed a significantly greater number of cells in G2 phase, 24 h post irradiation, than observed in controls. A more prolonged delay in G2 phase after irradiation was seen in different A-T cell types that included lymphoblastoid cells, fibroblasts and SV40-transformed fibroblasts. At the radiation dose used it was not possible to distinguish A-T heterozygotes from controls.
Mutat Res 1989 Sep
PMID:Comparison of gamma-radiation-induced accumulation of ataxia telangiectasia and control cells in G2 phase. 254 9

In this short article, Raymond Peterson and Jane Funkhouser develop the argument that the common molecular mechanism linking the various clinical manifestations of ataxia-telangiectasia (AT) is a defect in the regulation of the immunoglobulin (Ig) gene superfamily. They propose that the AT gene codes for a protein essential for the orderly expression of this gene family, perhaps regulating the gene rearrangement process that appears to be a unique characteristic of this system. Members of the Ig gene superfamily play a major role in the development and operation of the immune and nervous systems, and any perturbation of their expression would be anticipated to produce a panoply of signs and symptoms, such as those characterizing the AT phenotype.
Immunol Today 1989 Sep
PMID:Speculations on ataxia-telangiectasia: defective regulation of the immunoglobulin gene superfamily. 268 80

The effect of hydrogen peroxide on the rate of semi-conservative DNA synthesis in ataxia telangiectasia (AT) and normal human lymphoblastoid cells was investigated. The rate of DNA synthesis in AT cells was not depressed to a lesser extent than in normal cells, as might have been expected since H2O2 is a radiomimetic agent. On the contrary, 4 AT cell lines displayed a higher sensitivity to the inhibitory effect of H2O2 on DNA synthesis than 2 normal cell lines. Comparable levels of cytotoxicity were detected in cell viability studies. Furthermore, neither the level of DNA breakage produced by H2O2, nor the rate of repair of these lesions was significantly different in normal and AT cells. Together, these results indicate that the AT cell lines utilized in this study are not hypersensitive to the oxidant. It is suggested that H2O2 may not induce lethality via the direct action of the hydroxyl radical (OH.).
Mutat Res 1989 Sep
PMID:Identification of 4 ataxia telangiectasia cell lines hypersensitive to gamma-irradiation but not to hydrogen peroxide. 277 Jul 63

The objective of this study was to obtain an estimate of the frequency distribution of spontaneous chromosomal breakage occurring in vivo in oral epithelia of 20 ataxia-telangiectasia patients (A-T homozygotes) and 26 parents (A-T obligate heterozygotes). Samples of exfoliated cells were obtained from each individual by swabbing the oral cavity and preparing air-dried slides. The percentage of exfoliated cells with micronuclei (MEC frequency) was used as an in vivo indicator for the amount of chromosomal breakage occurring in the tissue. As a population group, MEC frequencies of the A-T patients differed significantly from controls (mean for A-T patients, 1.51; for controls, 0.29; P less than 0.01). However, the values observed in individual patients ranged from MEC frequencies 10- to 12-fold above control values, to frequencies overlapping the upper values observed in the controls. Similarly, MEC frequencies observed among the A-T heterozygotes differed significantly from controls (mean for A-T heterozygotes, 1.02, mean for controls, 0.29; P less than 0.01). However, only 16 of the 26 individuals sampled had MEC frequencies greater than 0.5%, the 90th percentile for controls (compared with 16 of the 20 A-T patients examined). Of the A-T patients 11 had been previously assigned to complementation groups on the basis of sensitivity to x-irradiation. Seven of the patients belonged to group A and had MEC frequencies ranging from 0.3% to 1.9% with the remaining patients belonging to group C with MEC frequencies of 0.2% to 0.9%. The data presented in this paper suggest that although levels of spontaneous breakage in epithelial tissues of A-T patients and A-T obligate heterozygotes are often significantly elevated, this is not the case in all individuals.
Hum Genet 1989 Sep
PMID:Heterogeneity of chromosomal breakage levels in epithelial tissue of ataxia-telangiectasia homozygotes and heterozygotes. 277 52


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>