Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0032463 (polycythemia vera)
 3,374 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have mutagenized and mapped the gene encoding the large subunit of ribonucleotide reductase (RR1) in pseudorabies virus (PRV; synonyms Aujeszky's disease virus, suid herpesvirus type 1). PRV strains carrying an oligonucleotide that leads to termination of translation of the RR1 gene are avirulent for mice. We subsequently constructed a PRV strain carrying a deletion in the RR1 gene and also a PRV strain carrying both the deletion in the RR1 gene and a deletion in the glycoprotein g1 gene, which is a marker for PRV virulence. Both PRV strains were assayed for virulence and immunogenicity in pigs, the natural host for PRV. In contrast to a marker-rescued PRV strain, these RR1-deleted mutants were avirulent, were shed in very low titres in the oropharyngeal fluid by the animals, and induced low titres of neutralizing antibodies. However, protection against clinical signs after infection with virulent PRV was induced by both RR1-deleted mutants. The relative importance of viral RR and thymidine kinase enzymes for deoxynucleotide synthesis in viral replication is discussed. In addition, we discuss the potential use of RR as a target for anti-herpesviral drugs and the use of PRV strains, deleted for the RR1 gene, as vaccine strains.
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PMID:Ribonucleotide reductase-deficient mutants of pseudorabies virus are avirulent for pigs and induce partial protective immunity. 838 70

Oxygen tension in healing tissues is heterogeneous. Increased oxygen mostly stimulates repair mechanisms and enhances tissue healing. Hyperbaric oxygen therapy increases blood and tissue oxygen content and may help maintain cellular integrity and function. Hydroxyurea (HU) is a cytotoxic agent, which leads to inactivation of ribonucleotide reductase, inhibition of cellular DNA synthesis, and cell death in the S phase. HU induced leg ulcers occur after use of this agent for a long time and at higher cumulative doses. Here we describe a diabetic patient with foot ulcer associated with HU treatment for polycythemia vera, who was treated successfully with hyperbaric oxygen and general wound care after discontinuation of HU. Faster improvement of leg ulcer in our patient compared to literature regarding HU withdrawal as single therapy suggests that hyperbaric oxygen may be helpful in the management of HU associated leg ulcers, especially in diabetic subjects.
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PMID:Hydroxyurea associated leg ulcer succesfully treated with hyperbaric oxygen in a diabetic patient. 1731 77

Hydroxyurea (HU) is a ribonucleotide reductase inhibitor used to treat myeloproliferative diseases including polycythemia vera (PV) and essential thrombocythemia (ET). We describe an 82-year-old male who was started on HU 500 mg three times weekly for the treatment of PV. Eight days after initiation of HU he experienced anorexia, nausea, vomiting, fever, fatigue, dizziness, and shaking chills. Discontinuation of the HU resulted in resolution of his symptoms within 2 days, and HU was re-started. Ten days after re-starting HU, the patient re-presented with nausea and anorexia. Lab tests revealed elevations in liver enzyme function tests, which resolved promptly after cessation of HU. Patients being initiated on HU should be advised that rarely, fevers, chills, nausea, and elevations in liver function tests may occur.
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PMID:Hydroxyurea induced acute elevations in liver function tests. 1833 43

Nonmelanoma skin cancer is the most common malignant tumor in the fair skin population, with each year several millions of diagnosed cases. Their most common risk factors are fair skin, a history of excessive ultraviolet light exposure, chronic inflammatory skin conditions, exposure to radiation, and contact with arsenic. Certain drugs can also be associated with a higher risk of nonmelanoma skin cancer. These include hydroxyurea, which acts as a metabolic inhibitor of ribonucleotide reductase and a potent nonalkylating myelosuppressive agent. It is used for the treatment of various myeloproliferative disorders, including chronic myeloid leukemia, polycythemia vera, and essential thrombocytopenia. Several publications describe an increased occurrence of skin manifestations following hydroxyurea treatment. A growing body of evidence indicates a possible role of hydroxyurea in skin cancer progression. In this review article, we summarize some relevant observations about the association of hydroxyurea and skin cancer, and we describe our own clinical experiences to provide up to date recommendations about the care of patients on hydroxyurea therapy.
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PMID:Nonmelanoma skin cancer associated with Hydroxyurea treatment: Overview of the literature and our own experience. 3136 87