Article

Megaloblastic Anemia and Other Causes of Macrocytosis

Department of Internal Medicine, Marshfield Clinic, 1000 North Oak Avenue, Marshfield, WI 54449, USA.
Clinical Medicine & Research 10/2006; 4(3):236-41. DOI: 10.3121/cmr.4.3.236
Source: PubMed

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Available from: ncbi.nlm.nih.gov
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    • "The two latter conditions lead to a delay in cell proliferation and to the formation of " trademark " large RBCs with an arrest in nuclear maturation. Bone marrow findings typically include large erythroblasts (megaloblasts) and hypercellularity[13]. Main morphological feature is macrocytosis which leads to classification in macrocytic anemias and in terms of laboratory findings is correlated with increased MCV. "
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    ABSTRACT: We herein would like to report an interesting case of a patient who presented with anemia and thrombocytopenia combined with high serum Lactic Dehydrogenase where Thrombotic Thrombocytopenic Purpura was originally considered. As indicated a central venous catheter was inserted in his subclavian vein which led to mediastinal hematoma and finally intubation and Intensive Care Unit (ICU) hospitalization. After further examination patient was finally diagnosed with B12 deficiency in a setting of H hemoglobinopathy. There have been previous reports where pernicious anemia was originally diagnosed and treated as Thrombotic Thrombocytopenic Purpura but there has been none to our knowledge that was implicated with hemothorax and ICU hospitalization or correlated with thalassemia and we discuss the significance of accurate diagnosis in order to avoid adverse reactions and therapy implications.
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    • "THF is a co-factor critical in the metabolism of amino acids and nucleic acids. The deficiency in THF (possibly caused by the deficiency in FOL) leads to megalobalstic anemia [42]. Therefore, the delivery of human DHFR variants efficiently catalyzing the conversion reaction of FOL or the human DHFR genes into megaloblastic anemia patients is a potential therapeutic strategy. "
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    ABSTRACT: As the number of reactions requiring biotransformation continues to grow, manipulating the enzyme substrate specificity becomes very important. Complementary to conventional enzyme engineering techniques based on only natural amino acids, we hypothesized that the site-specific incorporation of a non-natural amino acid in vivo into an enzyme can be used to re-design the active site for the altered substrate specificity. To test our hypothesis, we introduced the non-natural amino acid L-2-naphthylalanine (2Nal) into the active site of the model enzyme murine dihydrofolate reductase (mDHFR). We explored whether the substrate specificity of the enzyme could be switched from the good substrate dihydrofolate (DHF) to the poor substrate folate (FOL). We used two protein design programs (RosettaLigand and RosettaDesign) to calculate ligand docking and conformational stability, respectively, for the evaluation of multiples sites in the mDHFR. From the calculations, position 31 was predicted as an optimal 2Nal incorporation site. One mDHFR variant containing 2Nal at position 31 (mDHFR2Nal31) was expressed in the Escherichia coli expression host cells equipped with the engineered yeast phenylalanyl-tRNA and phenylalanyl-tRNA synthetase pair. As expected, the kinetic assays of purified mDHFR variant revealed that mDHFR2Nal31 has the enhanced binding affinity toward FOL and also exhibits 7.6-fold enhanced catalytic efficiency of FOL over DHF compared to mDHFRWT.
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    • "When Cbl is deficient, red blood cell membrane rigidity increases and erythrocyte deformability decreases[2]. These changes ultimately result in cell lysis, causing hemolytic anemia, and elevation of serum LDH levels[3]. LDH levels appear to be markedly higher among persons with MAHA due to Cbl deficiency versus TTP[1,4]. Cbl deficiency also causes elevated homocysteine levels, which leads to endothelial dysfunction and results in fragmentation of erythrocytes to schistocytes[5].In 2011, Tadakamalla et al.described a patient with PA who was initially diagnosed with TTP based on hemolysis, thrombocytopenia and numerous schistocytes being identified in the initial peripheral blood smear. "

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