Detection of somatic mutations of the PIG-A gene in Brazilian patients with paroxysmal nocturnal hemoglobinuria

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal syndrome characterized by intravascular hemolysis mediated by complement, thrombotic events and alterations in hematopoiesis. Basically, the molecular events which underlie the complexity of the syndrome consist of the absence of the glycosylphosphatidylinositol (GPI) anchor as a consequence of somatic mutations in the PIG-A gene, located on the X chromosome. The GPI group is responsible for the attachment of many proteins to the cytoplasmic membrane. Two of them, CD55 and CD59, have a major role in the inhibition of the action of complement on the cellular membrane of blood cells. The absence of GPI biosynthesis can lead to PNH. Since mutations in the PIG-A gene are always present in patients with PNH, the aim of this study was to characterize the mutations in the PIG-A gene in Brazilian patients. The analysis of the PIG-A gene was performed using DNA samples derived from bone marrow and peripheral blood. Conformation-sensitive gel electrophoresis was used for screening the mutation and sequencing methods were used to identify the mutations. Molecular analysis permitted the identification of three point mutations in three patients: one G->A transition in the 5' portion of the second intron, one T->A substitution in the second base of codon 430 (Leu430->stop), and one deletion deltaA in the third base of codon 63. This study represents the first description of mutations in the PIG-A gene in a Brazilian population.76376

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time, and attempts to address it require a clear understanding of how ecological communities respond to environmental change across time and space. While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes, vast areas of the tropics remain understudied. In the American tropics, Amazonia stands out as the world's most diverse rainforest and the primary source of Neotropical biodiversity, but it remains among the least known forests in America and is often underrepresented in biodiversity databases. To worsen this situation, human-induced modifications may eliminate pieces of the Amazon's biodiversity puzzle before we can use them to understand how ecological communities are responding. To increase generalization and applicability of biodiversity knowledge, it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple organism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region's vulnerability to environmental change. 15%–18% of the most neglected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lost

Hairy-cell Leukemia And Glucose-6-phosphate Dehydrogenase [1]

[No abstract available]33557

Hairy Cell Leukemia And Multipe Autoimmune Manifestations In A Human Immunodeficiency Virus-infected Patient

Aggressive B-cell lymphomas are clearly related to HIV infection. However, the relationship of HIV infection to low-grade B- or T-cell lymphomas and Hodgkin's disease is not well established. The authors describe a case in which hairy cell leukemia was associated with lupus anticoagulant and direct Coombs' test in an HIV-positive patient.66632532

Acute Myocardial Infarction In Sickle Cell Anaemia Associated With Severe Hypoxia

A 17 year old boy with sickle cell anaemia presented with acute myocardial infarction associated with severe hypoxia and reticulocytopenia. Ischaemic heart disease is rare in sickle cell anaemia and in this case it is possible that the acute episode of hypoxia led to myocardial infarction.667821068107

Rapid Detection Of Factor V Leiden (fvq506) By Non-radioactive Single Strand Conformation Polymorphism (sscp)

The transition G→A at position 506 of the factor V gene is responsible for resistance to the anticoagulant effect of activated protein C (APC-resistance), and represents the most common hereditary risk factor for venous thrombosis. A comparison of the ability of non-radioactive single-strand conformation polymorphism (SSCP) and of a standard PCR procedure followed by further digestion with MnlI to detect this factor V gene (FVQ 506) transition indicates that these is a good agreement between the two methods. Non-radioactive SSCP analysis therefore represents a rapid and sensitive alternative for the diagnosis of this important point mutation.415379381Anderson, F.A., Wheeler, B., Goldberg, R.J., Hosmer, D.W., Forcier, A., Patwardhan, N.A., Physician practices in the prevention of venous thromboembolism (1993) Ann Int Med, 115, pp. 591-595Colman, R.W., Hirsh, J., Marder, V.J., Salzman, E.W., Hemostasis and Thrombosis (1994) Basic Principles and Clinical Practice, 3rd Edn, , Lippincott, PhiladelphiaBauker, K.A., Rosenberg, R.D., The hypercoagulable state (1991) Disorders of Hemostasis 2nd Edn., pp. 267-291. , Ratnoff OD & Forbes CD ed. Saunders, PhiladelphiaDahlback, B., Carlsson, M., Svensson, P.J., Familial thrombophilia due to a previously unrecognized mechanism characterized by poor anticoagulant response to activated protein C: Prediction of a cofactor to activated protein C (1993) Proc Natl Acad Sci USA, 90, pp. 1004-1008Koster, T., Rosendaal, F.R., Ronde, H., Briét, E., Vandenbroucke, J., Bertina, R.M., Venous thrombosis due to poor anticoagulant response to activated protein C: Leiden Thrombophilia Study (1993) Lancet, 342, pp. 1503-1506Griffin, J.H., Evatt, B., Wideman, C., Fernández, J.A., Anticoagulant protein C pathway defective in majority of thrombophilic patients (1993) Blood, 82, pp. 1989-1993Svensson, P.J., Dahlbäck, B., Resistance to activated protein C as a basis for venous thrombosis (1994) N Engl J Med, 330, pp. 517-522Bertina, R.M., Koelemann, B.P.C., Koster, T., Rosendaal, F.R., Dirven, R.J., Ronde, H., Mutation in blood coagulation factor V associated with resistance to activated protein C (1994) Nature, 369, pp. 64-67Orita, M., Iwahana, H., Kanazawa, H., Hayashi, K., Sekiya, T., Detection of polymorphisms of human DNA by gel electrophoresis as single-strand conformation polymorphisms (1989) Proc Natl Acad Sci USA, 86, pp. 2766-2770Grompe, M., The rapid detection of unknown mutation in nucleic acids (1993) Nature Genetics, 5, pp. 111-117Sugano, K., Kyogoku, A., Fukayama, N., Ohkura, H., Shimosato, Y., Sekiya, T., Hayashi, K., Rapid and simple detection of c-Ki-ras2 gene codon 12 mutations by nonradioisotopic single-strand conformation polymorphism analysis (1993) Lab Invest, 68, pp. 361-366Arruda, V.R., Annichini-Bizzacchi, J.M., Costa, F.F., Reitsma, P.H., Factor, V., Leiden (FVQ506) is common in Brazilian population (1995) Am J Hematol, 39, pp. 242-243Millar, S.A., Dykes, D.D., Polesky, H.F., A simple salting out procedure for extracting DNA from nucleated cell (1988) Nucleic Acids Res, 16, p. 1215Saiki, R.K., Gelfand, D.H., Stoffel, S., Scharf, S.J., Higushi, R., Horn, G.T., Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase (1983) Science, 239, pp. 487-491Lunghi, B., Iacoviello, L., Gemmati, D., Dilasio, M.G., Castoldi, E., Pinotti, M., Detection of new polymorphic markers in the factor V gene: Association with factor V levels in plasma (1996) Thromb Haemostas, 75, pp. 45-48Engel, H., Zwang, L., VanHiet, H.H.D.M., Michiels, J.J., Stibbe, J., Lindemans, J., Phenotyping and genotyping of coagulation factor V Leiden (1996) Thromb Haemostas, 75, pp. 267-26