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Biomedical subjects

Claire Harrison

Publications and source records attributed to Claire Harrison.

12 recordsLinked to original sources
PubMed2006

A family with erythrocytosis establishes a role for prolyl hydroxylase domain protein 2 in oxygen homeostasis.

The number of red blood cells is normally tightly regulated by a classic homeostatic mechanism based on oxygen sensing in the kidney. Decreased oxygen delivery resulting from anemia induces the production of erythropoietin, which increases red cell production and hence oxygen delivery. Investigations of erythropoietin regulation identified the transcription factor hypoxia-inducible factor (HIF). HIF is now recognized as being a key regulator of genes that function in a comprehensive range of processes besides erythropoiesis, including energy metabolism and angiogenesis. HIF itself is regulated through the alpha-subunit, which is hydroxylated in the presence of oxygen by a family of three prolyl hydroxylase domain proteins (PHDs)/HIF prolyl hydroxylases/egg-laying-defective nine enzymes. Hydroxylation allows capture by the von Hippel-Lindau tumor suppressor gene product, ubiquitination, and destruction by the proteasome. Here we describe an inherited mutation in a mammalian PHD enzyme. We show that this mutation in PHD2 results in a marked decrease in enzyme activity and is associated with familial erythrocytosis, identifying a previously unrecognized cause of this condition. Our findings indicate that PHD2 is critical for normal regulation of HIF in humans.

Adult↗
PubMed2005

Egocentric disorientation following bilateral parietal lobe damage.

Aguirre and D'Esposito (1999) suggested a taxonomy and theoretical framework for understanding topographical disorders. One of the problems they described involved egocentric disorientation, in which deficits are not strictly confined to the topographical sphere but are seen on a wide variety of visuo-spatial paradigms. Here, we report a neuropsychological investigation of MU, a person with egocentric disorientation. To test the usefulness of Aguirre and D'Esposito's framework, we administered tests which were predicted to be easy or difficult for people with egocentric disorientation to show that MU was impaired on tasks sensitive to egocentric disorientation and that he showed adequate performance on tests sensitive to other types of topographical representation. Thus MU showed normal performance on a test of recognition of famous landmarks and he could identify photographs of personally familiar places in his home town, yet he could not say how to get from a recognised building to another place in his environment. His performance fulfils the criteria for egocentric disorientation and fits the predictions derived from Aguirre and D'Esposito's views.

Adult↗
PubMed2005

Essential thrombocythemia.

Significant progress in our understanding of the molecular pathogenesis of essential thrombocythemia (ET) and the other Philadelphia (Ph) chromosome-negative myeloproliferative disorders (MPDs) has recently been achieved. Unfortunately, the diagnosis of ET still relies on a set of exclusion criteria developed years ago, as recent advances have yet to be evaluated for this purpose. The clinical course of ET is characterized by an increased incidence of thrombotic and hemorrhagic complications and an inherent tendency to progress into myelofibrosis or acute myeloid leukemia (AML). There is concern about undesirable effects of cytoreductive therapy given to prevent vascular events, particularly the risk of accelerating the rate of hematologic transformation. Thus, management involves modification of reversible vascular risk factors and further stratification according to the thrombotic risk. Myelosuppressive agents are not recommended in low-risk patients, whereas controlled studies support the therapeutic value of hydroxyurea (HU) plus aspirin in high-risk cases. Anagrelide or interferon-alpha (IFN-alpha) could be considered as second-line therapy in patients refractory or intolerant of HU. IFN-alpha is preferred in pregnant women.

Adult↗
PubMed2005

Pregnancy and its management in the Philadelphia negative myeloproliferative diseases.

The myeloproliferative diseases (MPDs) present several therapeutic challenges in patients of childbearing potential. The most extensive literature exists for patients with essential thrombocythaemia, with over 200 pregnancies reported in retrospective case series. Yet there is conflicting data in relation to predicting pregnancy outcome and optimal management strategy. Pregnancy is less frequently reported for polycythaemia vera and myelofibrosis. There is a need for collaboration to further our knowledge in this field. Here, the literature is reviewed in detail and experience of different therapeutic strategies in pregnancy discussed. There is increasing understanding about the pathogenesis of placental dysfunction in inherited thrombophilia and antiphospholipid antibody syndrome pregnancy outcomes in these conditions parallel those reported for MPDs. Furthermore several large studies have influenced pregnancy management in these conditions and, whilst not directly applicable to MPDs, this data have potential to inform treatment protocols. This data are reviewed and a personal management strategy for pregnancy in MPD proposed.

Female↗