Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018799 (heart disease)
 34,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Werner syndrome is a rare autosomal recessive disease characterized by a premature aging phenotype, genomic instability, and a dramatically increased incidence of cancer and heart disease. Mutations in a single gene encoding a 1432-amino acid helicase/exonuclease (hWRN) have been shown to be responsible for the development of this disease. We have cloned, overexpressed, and purified a minimal, 171-amino acid fragment of hWRN that functions as an exonuclease. This fragment, encompassing residues 70-240 of hWRN (hWRN-N(70-240)), exhibits the same level of 3'-5' exonuclease activity as the previously described exonuclease fragment encompassing residues 1-333 of the full-length protein. The fragment also contains a 5'-protruding DNA strand endonuclease activity at a single-strand-double-strand DNA junction and within single-stranded DNA, as well as a 3'-5' exonuclease activity on single-stranded DNA. We find hWRN-N(70-240) is in a trimer-hexamer equilibrium in the absence of DNA when examined by gel filtration chromatography and atomic force microscopy. Upon addition of DNA substrate, hWRN-N(70-240) forms a hexamer and interacts with the recessed 3'-end of the DNA. Moreover, we find that the interaction of hWRN-N(70-240) with the replication protein PCNA also causes this minimal, 171-amino acid exonuclease region to form a hexamer. Thus, the active form of this minimal exonuclease fragment of human WRN appears to be a hexamer. The implications these results have on our understanding of hWRN's roles in DNA replication and repair are discussed.
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PMID:A minimal exonuclease domain of WRN forms a hexamer on DNA and possesses both 3'- 5' exonuclease and 5'-protruding strand endonuclease activities. 1186 28

Werner's syndrome is an autosomal recessive disorder resulting in premature aging. Most patients die in their fifth decade from malignancies or heart disease. The gene for Werner's syndrome (WRN) encodes a recQ helicase. Cells from patients with Werner's syndrome have increased sensitivity to DNA-damaging drugs in vitro. Here we present a patient with Werner's syndrome who developed severe chemotherapy-induced toxicity during treatment for acute myelogenous leukemia. We propose that lack of WRN resulted in increased sensitivity of the patient's cells to the toxicity of chemotherapy.
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PMID:Severe toxicity following induction chemotherapy for acute myelogenous leukemia in a patient with Werner's syndrome. 1601 64

Cell Communication and Adhesion has been fortunate to enlist two pioneers of epidermal and cardiac cell junctions, Kathleen Green and Mario Delmar, as Guest Editors of a two part series on junctional targets of skin and heart disease. Part 2 of this series begins with an overview from Dipal Patel and Kathy Green comparing epidermal desmosomes to cardiac area composita junctions, and surveying the pathogenic mechanisms resulting from mutations in their components in heart disease. This is followed by a review from David Kelsell on the role of desmosomal mutation in inherited syndromes involving skin fragility. Agnieszka Kobeliak discusses how structural deficits in the epidermal barrier intersect with the NFkB signaling pathway to induce inflammatory diseases such as psoriasis and atopic dermatitis. Farah Sheikh reviews the specialized junctional components in cardiomyocytes of the cardiac conduction system and Robert Gourdie discusses how molecular complexes between sodium channels and gap junction proteins within the perijunctional microdomains within the intercalated disc facilitate conduction. Glenn Radice evaluates the role of N-cadherin in heart. Andre Kleber and Chris Chen explore new approaches to study junctional mechanotransduction in vitro with a focus on the effects of connexin ablation and the role of cadherins, respectively. To complement this series of reviews, we have interviewed Werner Franke, whose systematic documentation the tissue-specific complexity of desmosome composition and pioneering discovery of the cardiac area composita junction greatly facilitated elucidation of the role of desmosomal components in the pathophysiology of human heart disease.
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PMID:Highlighting Kathleen Green and Mario Delmar, guest editors of special issue (part 2): junctional targets of skin and heart disease. 2485 68

Since 1929, when the first cardiac catheterization was safely performed in a human by Dr. Werner Forssmann (on himself), there has been a rapid progression of cardiac catheterization techniques and technologies. Today, these advances allow us to treat a wide variety of patients with congenital heart disease using minimally invasive techniques; from fetus to infants to adults, and from simple to complex congenital cardiac lesions. In this article, we will explore some of the exciting advances in cardiac catheterization for the treatment of congenital heart disease, including transcatheter valve implantation, hybrid procedures, biodegradable technologies, and magnetic resonance imaging (MRI)-guided catheterization. Additionally, we will discuss innovations in imaging in the catheterization laboratory, including 3D rotational angiography (3DRA), fusion imaging, and 3D printing, which help to make innovative interventional approaches possible.
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PMID:Innovative interventional catheterization techniques for congenital heart disease. 2977 Feb 92