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

Employing the surface immunofluorescence technique and rosette test, surface receptors of lymphocytes from 83 healthy subjects (57 adult donors and 2l infants), 3 mature fetuses, and 110 patients, including 23 infants with acute repiratory infections, 22 patients with multiple sclerosis (MS), 20 patients with viral hepatitis (VH), 22 patients with chronic brucellosis, and 1 patient with ataxia-telangiectasia lacking serum IgA were studied. Surface immunoglobulins complement-receptor lymphocyte (B lymphocytes), rosette formation with uncoated sheep erythrocytes (T lymphocytes), and receptor for Fc IgG, characteristic mainly of B lymphocytes, were determined. Percentages of B lymphocytes in peripheral blood of adults (21%) and infants (about 24%), T lymphocytes in adults (about 70%) and infants (about 52%) were determined. On the surface of lymphocytes from adults, IgM predominated, followed by IgG, and IgA was least frequent. In acute upper respiratory tract infections in infants percentages of B lymphocytes in peripheral blood were markedly increased. Glucocorticoids used in treatment exerted a distinctly suppressive effect on these cells. In multiple sclerosis the number of cells with receptors for complement and density of receptors for Fc IgG on the surface of lymphocytes were decreased. In acute viral hepatitis, no significant changes in the contents of B and T lymphocytes in peripheral blood were noted. In chronic brucellosis, the numbers of T lymphocytes were decreased, and atypical mononuclear cells with partial lack of receptors typical of B lymphocytes were observed. The findings indicate that in diseases based on bacterial or viral infections and in multiple sclerosis, B and T lymphocytes play an essential role, which is reflected by the percentages of B and T lymphocytes in peripheral blood.
Ann Med Sect Pol Acad Sci 1975
PMID:Immunologic heterogeneity of the lymphocyte surface in various diseases. 110 13

The Nijmegen breakage syndrome (NBS) is a rare autosomal recessive disease, which belongs to the family of genetically determined instability syndromes and to the growing category of ataxia telangiectasia (AT)--related disorders. The main manifestations include pronounced microcephaly with mental retardation in most patients, "bird-like" facies, growth retardation, immunodeficiency, chromosome instability with multiple chromosome 7 and 14 rearrangements, hypersensitivity to ionizing radiation and normal AFP level. In light of high predisposition to malignancy, an accurate diagnosis is very important for the patient.
Pediatr Pol 1996 Mar
PMID:[Microcephaly with chromosomal instability and immunodeficiency--Nijmegen syndrome]. 896 94

The aim of this study was to compare the potential antithrombotic action of captopril (angiotensin converting enzyme inhibitor) and losartan (a selective AT1 receptor antagonist) after their chronic administration in a model of venous thrombosis in rats. Captopril significantly reduced the incidence of venous thrombosis (67% vs 14%; p < 0.05) and both drugs markedly reduced the weight of thrombus. At the same time the platelet aggregation was reduced only in rats treated with losartan (100 +/- 7% vs 52 +/- 11%; p < 0.001). The mean blood pressure dropped only after losartan administration. We observed no changes in "transection" bleeding time after both drugs administration. In conclusion, captopril and losartan exerted an antithrombotic effect in venous thrombosis model in rats. The precise mechanism of this action should be established.
Pol J Pharmacol
PMID:Effects of drugs affecting the renin-angiotensin system on venous thrombosis in normotensive rats. 911 34

Endothelial cells produce both vasodilatating compounds as nitric oxide, prostacycline, endothelial derived hyperpolarising factor and counteracting substances known as endothelial derived contracting factors: endothelin, tromboxan A2, prostaglandin H2, free oxygen radicals. Natural balance between both groups affects blood perfusion of various tissues and constitutes important element in blood pressure control. More and more attention is paid to endothelial dysfunction in patogenesis of hypertension. In a number of studies endothelial dysfunction in hypertensive patients was found out as decreased release of nitric oxide or increased production of endothelin. Principle mechanism of impaired function of endothelium in hypertension seems to be decreased production and increased degradation of nitric oxide mainly due to free oxygen radicals. Favorable effects in improvement of endothelial function were achieved by using ACE inhibitors, AT1 receptor blockers and calcium channel antagonists.
Pol Merkur Lekarski 2002 Apr
PMID:[Endothelial dysfunction in hypertension--clinical implications]. 1208 1

Ultraviolet (UV) irradiation produces DNA photoproducts that are blocks to DNA replication by normal replicative polymerases. A specialized, damage-specific, distributive polymerase, Pol H or Pol h, that is the product of the hRad30A gene, is required for replication past these photoproducts. This polymerase is absent from XP variant (XP-V) cells that must employ other mechanisms to negotiate blocks to DNA replication. These mechanisms include the use of alternative polymerases or recombination between sister chromatids. Replication forks arrested by UV damage in virus transformed XP-V cells degrade into DNA double strand breaks that are sites for recombination, but in normal cells arrested forks may be protected from degradation by p53 protein. These breaks are sites for binding a protein complex, hMre11/hRad50/Nbs1, that colocalizes with H2AX and PCNA, and can be visualized as immunofluorescent foci. The protein complexes need phosphorylation to activate their DNA binding capacity. Incubation of UV irradiated XP-V cells with the irreversible kinase inhibitor wortmannin, however, increased the yield of Mre11 focus-positive cells. One interpretation of this observation is that two classes of kinases are involved after UV irradiation. One would be a wortmannin-resistant kinase that phosphorylates the Mre11 complex. The other would be a wortmannin-sensitive kinase that phosphorylates and activates the p53/large T in SV40 transformed XP-V cells. The sensitive class corresponds to the PI3-kinases of ATM, ATR, and DNA-PK, but the resistant class remains to be identified. Alternatively, the elevated yield of Mre11 foci positive cells following wortmannin treatment may reflect an overall perturbation to the signaling cascades regulated by wortmannin-sensitive PI3 related kinases. In this scenario, wortmannin could compromise damage inducible-signaling pathways that maintain the stability of stalled forks, resulting in a further destabilization of stalled forks that then degrade, with the formation of DNA double strand breaks.
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PMID:DNA replication arrest in XP variant cells after UV exposure is diverted into an Mre11-dependent recombination pathway by the kinase inhibitor wortmannin. 1245 48

The renin-angiotensin-aldosterone system plays an important role in the regulation of electrolyte balance, body fluid volume and blood pressure. As yet, angiotensin II has been ascribed actions mediated by first type of receptors (AT1) such as increased blood pressure, antinatriuretic effect, cell proliferation. Since several years studies have been conducted on the role of second type receptor (AT2) through which angiotensin manifests its effects opposing those resulting from stimulation of type 1 receptor. They include: release of bradykinin and nitric oxide, vasodilation, natriuretic and antiproliferative effects. Blockade of the function of this receptor causes excessive reaction induced by action exerted on AT1 receptor.
Pol Merkur Lekarski 2003 Feb
PMID:[Unexpected properties of angiotensin mediated by the AT2 receptor: possible therapeutic implications]. 1272 64

It is suggested that vasoconstriction mediated by angiotensin II cleaved from angiotensin I by angiotensin converting enzyme (ACE) is counterbalanced by concomitant formation of vasodilator angiotensin (1-7) by neutral endopeptidase (NEP). Here, we tested this hypothesis using as a bioassay the isolated rat lung perfused with Krebs-Henseleit (KH) solution and ventilated with negative pressures. Addition of angiotensin I (100 nM) into the isolated lung resulted in an immediate increase in pulmonary arterial pressure (Delta PAP) which was not accompanied by a significant change in respiratory lung function or weight of the lung. The Delta PAP response induced by angiotensin I was abolished by an inhibitor of ACE, perindoprilate (1 microM), or by angiotensin type 1 receptor antagonist (losartan, 1 microM) but not by angiotensin type 2 receptor antagonist (PD 123.319, 10 microM) suggesting the involvement of ACE and AT1 (but not AT2) receptors in this response. On the other hand, antagonist of bradykinin receptor B2 (icatibant, 100 nM) or an inhibitor of neutral endopeptidase, thiorphan (1 microM and 10 microM) did not modify DeltaPAP response induced by angiotensin I. In summary, in the isolated rat lung perfused with KH solution, ACE has a dominant role in the pulmonary conversion of angiotensin I to angiotensin II, while NEP-derived angiotensin 1-7 does not seem to constitute a major counterbalancing mechanism in the pulmonary vasoconstriction induced by endogenously formed angiotensin II.
Pol J Pharmacol
PMID:Effect of neutral endopeptidase inhibition on vascular response induced by exogenous angiotensin I in the isolated rat lung. 1473 Jan 3

Ataxia-telangiectasia (AT) is the primary immunodeficiency with chromosomal instability. AT is a multisystem, autosomal recessive disorder characterised by progressive cerebellar ataxia, oculocutaneous telangiectasia, and increased susceptibility to recurrent respiratory tract infections and cancer predisposition. The cells from AT patients are radiosensitive to ionizing radiation and DNA repair damage. The gene responsible for AT is localised at chromosome 11q23.1, and encodes protein ATM that is important in the cell cycle control. In AT, both the humoral and cellular immune systems are affected including deficiency of serum IgA (70% of patients), IgG2 and IgG4, and deficiency of serum IgG (30% of patients). Functional tests of lymphocytes T revealed poor proliferative responses to phytohemagglutinin.
Neurol Neurochir Pol 2004
PMID:[Ataxia telangiectasia syndrome: clinical picture and immunological abnormalities]. 1504 61

Among the causes of premature ovarian failure (POF) two groups of factors are reported: factors which lead to decrease of follicular number and factors which stimulate follicular atresia. In the first group genetic factors are the most important whereas in the second: enzymatic autoimmunological, iatrogenic, toxins and infections are reported. In 1986 familiar POF on the background of long arm of chromosome X deletion was reported. Other chromosomes which are important for normal ovarian function are: chromosome 21 (AIRE gene), chromosome 11 (gene of beta FSH, ATM gene), chromosome 3 (gene responsible for BEPS syndrome) and chromosome 2 (genes of FSH and LH receptors). In this review the role of these genes and results of several epidemiological studies are reported.
Endokrynol Pol
PMID:[Genetic aspects of premature ovarian failure]. 1635 Jul 32

Ataxia-telangiectasia mutated (ATM), ataxia-telangiectasia Rad3-related (ATR) and the Mre11/Rad50/Nbs1 complex ensure genome stability in response to DNA damage. However, their essential role in DNA metabolism remains unknown. Here we show that ATM and ATR prevent accumulation of DNA double-strand breaks (DSBs) during chromosomal replication. Replicating chromosomes accumulate DSBs in Xenopus laevis egg extracts depleted of ATM and ATR. Addition of ATM and ATR proteins to depleted extracts prevents DSB accumulation by promoting restart of collapsed replication forks that arise during DNA replication. We show that collapsed forks maintain MCM complex but lose Pol epsilon, and that Pol epsilon reloading requires ATM and ATR. Replication fork restart is abolished in Mre11 depleted extracts and is restored by supplementation with recombinant human Mre11/Rad50/Nbs1 complex. Using a novel fluorescence resonance energy transfer-based technique, we demonstrate that ATM and ATR induce Mre11/Rad50/Nbs1 complex redistribution to restarting forks. This study provides direct biochemical evidence that ATM and ATR prevent accumulation of chromosomal abnormalities by promoting Mre11/Rad50/Nbs1 dependent recovery of collapsed replication forks.
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PMID:ATM and ATR promote Mre11 dependent restart of collapsed replication forks and prevent accumulation of DNA breaks. 1660 1


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