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Interdisciplinary Toxicology Mar 2014Pyrethroids, commercially available pesticides, are greatly in use these days, and thus they carry considerable chances of contaminating various ecosystems....
Pyrethroids, commercially available pesticides, are greatly in use these days, and thus they carry considerable chances of contaminating various ecosystems. Haematotoxicity of cypermethrin, a broadly used type II pyrethroid, has been assessed in the present study. Selected parameters included determination of total RBC count, haemoglobin concentration (Hb conc.), packed cell volume (PCV), mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH), mean corpuscular haemoglobin concentration (MCHC), erythrocyte sedimentation rate (ESR), total leukocyte count (TLC), differential leukocyte count (DLC), along with qualitative analysis of blood and bone marrow. Of these parameters, those showing significant decline following cypermethrin intoxication included total RBC count, Hb conc., PCV, MCV, MCH, whereas non-significant decrease was observed in the case of MCHC. ESR, TLC and DLC, on the other hand, increased significantly following cypermethrin intoxication. Qualitative changes included altered red cell morphology such as microcystosis, appearance of stomatocytes, poikilocytosis, giant platelet formation, etc. in peripheral blood and increased erythroid precursors in bone marrow of treated rats. These parameters were however normalised following twenty-two days of recovery phase.
PubMed: 26038674
DOI: 10.2478/intox-2014-0006 -
Haematologica Mar 2008beta-thalassemia is one of the most common genetic diseases in the world and requires extensive therapy. Lentiviral-mediated gene therapy has been successfully exploited...
BACKGROUND
beta-thalassemia is one of the most common genetic diseases in the world and requires extensive therapy. Lentiviral-mediated gene therapy has been successfully exploited in the treatment of beta-thalassemia and showed promise in clinical application. Using a human beta-globin transgenic mouse line in a beta-thalassemia diseased model generated with a lentiviral-mediated approach, we investigate the stable therapeutic effect on a common thalassemia syndrome.
DESIGN AND METHODS
Human beta-globin gene lentiviral vector was constr ucted, followed by subzonal microinjection into single-cell embryos of beta(IVS-2-654)-thalassemia mice to generate a transgenic line. Human beta-globin gene expression was examined with RT-PCR, Western-blotting and ELISA. The hematologic parameters and tissue pathology were investigated over time in founder mice and their off-spring.
RESULTS
Transgenic mice with stable expression of the lentivirus carrying human beta-globin gene were obtained. A marked improvement in red blood cell indices and a dramatic reduction in red blood cell anisocytosis, poikilocytosis and target cells were observed. Nucleated cell proportion was greatly decreased in bone marrow, and splenomegaly with extramedullary hematopoiesis was ameliorated. Iron deposition in liver was also reduced. There was a two-fold increase in the survival rate of the beta(IVS-2-654) mice carrying human beta-globin transgene. Significantly, the germline integration of the lentiviral construct was obtained and stable hematologic phenotype correction was observed over the next two generations of the transgenic mice.
CONCLUSIONS
The generation of human beta-globin transgenic mice in a beta(IVS-2-654)-thalassemia mouse mediated with lentiviral vectors provides a useful model and offers an attractive means to investigate the transgenic stable therapeutic effect in beta-thalassemia.
Topics: Animals; Bone Marrow; Disease Models, Animal; Female; Genetic Therapy; Genetic Vectors; Germ-Line Mutation; Globins; Humans; Lentivirus; Liver; Male; Mice; Mice, Mutant Strains; Mice, Transgenic; Microinjections; Mutagenesis, Insertional; Recombinant Fusion Proteins; Spleen; Virus Integration; beta-Thalassemia
PubMed: 18268280
DOI: 10.3324/haematol.12010 -
Annales de Biologie Clinique 2007We report the case of a 59 year old man presenting a regenerative microcytic hypochromic anaemia. The investigations revealed the presence of haemoglobin H, suggesting...
We report the case of a 59 year old man presenting a regenerative microcytic hypochromic anaemia. The investigations revealed the presence of haemoglobin H, suggesting abnormalities in the alpha-globin chains synthesis. Alpha-thalassemia was thus suspected. The patient had no personal or familial history. The association with aniso-poïkilocytosis and a marked iron overload (ferritinemia > 1,500 microg/L) suggested a myelodysplastic syndrome, which was confirmed with a bone marrow aspiration. The pattern was consistent with the Acquired alpha-Thalassemia-Myelodysplastic Syndrome (ATMDS). About a hundred cases are listed worldwidely and collected in an international registry. The causes of ATMDS are ignored, but recent reports indicate that the ATRX gene may be implicated in the pathogenesis. ATRX is a chromatin-associated protein, involved in the transcription of several genes. The alpha globin genes could be one of the targets of the ATRX protein.
Topics: Anemia, Refractory; Erythrocytes; Hemochromatosis; Humans; Male; Middle Aged; Myelodysplastic Syndromes; alpha-Thalassemia
PubMed: 17627922
DOI: No ID Found -
Romanian Journal of Morphology and... 2007Atherosclerosis is a complex process that affects specific tissues of the vasculature, susceptible to developing atherosclerosis. >From 10 patients with atherosclerosis,...
Atherosclerosis is a complex process that affects specific tissues of the vasculature, susceptible to developing atherosclerosis. >From 10 patients with atherosclerosis, between 50-70 years, peripheral blood was prelevated and after the technical procedures the blood cells were studied using the electron microscopy. The most characteristic morphological modifications were observed in agranulocytes and platelets. The granulocytes polymorphs showed insignificant ultrastructural changes, and the erythrocytes presented weak anizocytosis and poikilocytosis.
Topics: Aged; Atherosclerosis; Blood Cells; Blood Platelets; Erythrocytes; Female; Humans; Hypertension; Leukocytes; Male; Microscopy, Electron, Transmission; Middle Aged; Myocardial Ischemia; Stroke
PubMed: 17502950
DOI: No ID Found -
Blood Dec 2006Actin oligomers are a significant structural component of the erythrocyte cytoskeleton. Rac1 and Rac2 GTPases regulate actin structures and have multiple overlapping as...
Actin oligomers are a significant structural component of the erythrocyte cytoskeleton. Rac1 and Rac2 GTPases regulate actin structures and have multiple overlapping as well as distinct roles in hematopoietic cells; therefore, we studied their role in red blood cells (RBCs). Conditional gene targeting with a loxP-flanked Rac1 gene allowed Crerecombinase-induced deletion of Rac1 on a Rac2 null genetic background. The Rac1(-/-);Rac2(-/-) mice developed microcytic anemia with a hemoglobin drop of about 20% and significant anisocytosis and poikilocytosis. Reticulocytes increased more than 2-fold. Rac1(-/-);Rac2(-/-) RBCs stained with rhodamine-phalloidin demonstrated F-actin meshwork gaps and aggregates under confocal microscopy. Transmission electron microscopy of the cytoskeleton demonstrated junctional aggregates and pronounced irregularity of the hexagonal spectrin scaffold. Ektacytometry confirmed that these cytoskeletal changes in Rac1(-/-);Rac2(-/-) erythrocytes were associated with significantly decreased cellular deformability. The composition of the cytoskeletal proteins was altered with an increased actin-to-spectrin ratio and increased phosphorylation (Ser724) of adducin, an F-actin capping protein. Actin and phosphorylated adducin of Rac1(-/-);Rac2(-/-) erythrocytes were more easily extractable by Triton X-100, indicating weaker association to the cytoskeleton. Thus, deficiency of Rac1 and Rac2 GTPases in mice alters actin assembly in RBCs and causes microcytic anemia with reticulocytosis, implicating Rac GTPases as dynamic regulators of the erythrocyte cytoskeleton organization.
Topics: Actin Cytoskeleton; Anemia; Animals; Calmodulin-Binding Proteins; Carrier Proteins; Erythrocyte Membrane; Mice; Mice, Knockout; Microfilament Proteins; Neuropeptides; Phosphorylation; Protein Processing, Post-Translational; Reticulocytes; Reticulocytosis; Spectrin; rac GTP-Binding Proteins; rac1 GTP-Binding Protein; RAC2 GTP-Binding Protein
PubMed: 16882712
DOI: 10.1182/blood-2006-03-005942 -
American Journal of Hematology Jan 2003Myelofibrosis is characterized by reticulin fibrosis of the bone marrow with resulting features of myelophthisis. Besides hematopoietic malignancies and other neoplasms...
Myelofibrosis is characterized by reticulin fibrosis of the bone marrow with resulting features of myelophthisis. Besides hematopoietic malignancies and other neoplasms involving the bone marrow, myelofibrosis has been described in association with autoimmune disorders, especially systemic lupus erythematosus. We describe the clinicopathologic features of a primary form of autoimmune myelofibrosis (AIMF) in patients who do not have systemic lupus erythematosus or another well-defined autoimmune syndrome. Absence of marked splenomegaly, peripheral blood cytopenias with mild teardrop poikilocytosis and leukoerythroblastosis, bone marrow lymphoid aggregates, and presence of autoantibodies are some of the salient features of primary AIMF. AIMF should especially be differentiated from chronic idiopathic myelofibrosis, a neoplastic myeloproliferative disease. Primary AIMF appears to have an excellent prognosis, with all patients reported in this series responding to a short course of corticosteroid therapy.
Topics: Adrenal Cortex Hormones; Adult; Aged; Autoantibodies; Autoimmune Diseases; Bone Marrow; Comorbidity; Diagnosis, Differential; Female; Fever; Fibrosis; Humans; Immunosuppressive Agents; Male; Megakaryocytes; Middle Aged; Primary Myelofibrosis; Spleen; Sweating
PubMed: 12508261
DOI: 10.1002/ajh.10258 -
Blood Aug 2000Absence of band 3, associated with the mutation Coimbra (V488M) in the homozygous state, caused severe hereditary spherocytosis in a young child. Although prenatal...
Absence of band 3, associated with the mutation Coimbra (V488M) in the homozygous state, caused severe hereditary spherocytosis in a young child. Although prenatal testing was made available to the parents, it was declined. Because the fetus stopped moving near term, an emergency cesarean section was performed and a severely anemic, hydropic female baby was delivered. She was resuscitated and initially kept alive with respiratory assistance and hypertransfusion therapy. Cord blood smears revealed erythroblastosis, poikilocytosis, and red cells with stalk-like elongations. Band 3 and protein 4.2 were absent; spectrin, ankyrin, and glycophorin A were significantly reduced. Renal tubular acidosis was detected by the age of 3 months. Nephrocalcinosis appeared soon thereafter. After 3 years of follow-up the child is doing reasonably well on a regimen that includes regular blood transfusions and daily bicarbonate supplements. The long-term prognosis remains uncertain given the potential for hematologic and renal complications. (Blood. 2000;96:1602-1604)
Topics: Acidosis, Renal Tubular; Anion Exchange Protein 1, Erythrocyte; Female; Gene Deletion; Humans; Spherocytosis, Hereditary
PubMed: 10942416
DOI: No ID Found -
Annales de Biologie Clinique 2000Myelodysplastic syndromes (MDS) are clonal disorders of pluripotent hematopoietic stem cells. MDS occur predominantly over the age of 60 years. The diagnosis of MDS is... (Review)
Review
Myelodysplastic syndromes (MDS) are clonal disorders of pluripotent hematopoietic stem cells. MDS occur predominantly over the age of 60 years. The diagnosis of MDS is based on the examination of both blood films and bone marrow aspirate. Diseases such as vitamin B12 and/or folate deficiency, or cytotoxic therapy leading to a marrow dysplasia should be ruled out. Five subtypes are described in the FAB classification : refractory anaemia or refractory cytopenia, refractory sideroblastic anaemia, refractory anaemia with excess of blasts, refractory anaemia with excess of blasts in transformation, chronic myelomonocytic leukaemia. This FAB classification is based on a small number of parameters: percentage of blood and marrow blasts, percentage of ringed sideroblasts and blood monocytes. The anaemia is typically normo- or macrocytic, non regenerative, and in half cases is associated with neutropenia and/or thrombocytopenia. During blood film examination, cell abnormalities have to be notified, i.e. anisocytosis, poikilocytosis of red cells, morphological abnormalities of neutrophils including hypogranulation, hypolobulation, abnormal large platelets. The prognostic and the treatment of MDS depend on the subtype of the FAB classification, the patient's age, the percentage of marrow blasts, the importance of cytopenia, the presence or not of cytogenetic abnormalities and the existence or not of HLA-identical donor.
Topics: Diagnosis, Differential; Hematopoietic Stem Cells; Humans; Myelodysplastic Syndromes
PubMed: 10932040
DOI: No ID Found -
Anemia, splenomegaly, and increased osmotic fragility of erythrocytes in Abyssinian and Somali cats.Journal of the American Veterinary... Nov 2000To determine clinical and clinicopathologic features of a chronic intermittent severe hemolytic anemia characterized by erythrocyte osmotic fragility in Abyssinian and...
OBJECTIVE
To determine clinical and clinicopathologic features of a chronic intermittent severe hemolytic anemia characterized by erythrocyte osmotic fragility in Abyssinian and Somali cats.
DESIGN
Case series.
ANIMALS
13 Abyssinian and 5 Somali cats.
PROCEDURES
History, pedigree information, and results of routine laboratory tests, special erythrocyte studies, and histologic evaluation of splenic and hepatic specimens were analyzed.
RESULTS
Age at which clinical signs of anemia were first apparent ranged from 6 months to 5 years. Ten cats had splenomegaly. Most often, the PCV was between 15 and 25%, but it was as low as 5% at some times. The anemia was characterized by macrocytosis and mild to moderate reticulocytosis, but no poikilocytosis. Hyperglobulinemia, lymphocytosis, mild hyperbilirubinemia, and high hepatic enzyme activities were common findings. Results of Coombs tests and tests for infectious diseases were negative. The erythrocytic osmotic fragility was high in affected cats (mean osmotic fragility, 0.66 to 0.78%), compared with healthy cats (0.48 to 0.58). No specific membrane protein abnormality, erythrocyte enzyme deficiency, or hemoglobinopathy was identified. Histologic evaluation of splenic and hepatic specimens revealed extramedullary hematopoiesis and hemosiderosis. Four of the 5 Somali cats were closely related.
CONCLUSIONS AND CLINICAL RELEVANCE
On the basis of results of pedigree analyses, the apparent breed predilection, and the exclusion of other known causes of anemia in cats, we believe that the hemolytic anemia in these cats was likely a result of a novel hereditary erythrocyte defect. A genetic predisposition to immune-mediated destruction of erythrocytes could not be ruled out.
Topics: Anemia, Hemolytic, Autoimmune; Animals; Blood Chemical Analysis; Cat Diseases; Cats; Chromatography, High Pressure Liquid; Coombs Test; Electrophoresis, Polyacrylamide Gel; Female; Hematocrit; Hemoglobins; Histocytochemistry; Liver; Male; Membrane Proteins; Microscopy, Electron; Osmotic Fragility; Pedigree; Pyruvate Kinase; Spleen; Splenomegaly
PubMed: 11128538
DOI: 10.2460/javma.2000.217.1483 -
Internal Medicine (Tokyo, Japan) May 1998We report a case of multiple diffuse fibrosarcoma of bone. The patient, a 38-year-old man, was referred to our hospital with knee pain, anemia and thrombocytopenia. No...
We report a case of multiple diffuse fibrosarcoma of bone. The patient, a 38-year-old man, was referred to our hospital with knee pain, anemia and thrombocytopenia. No solid mass was seen on radiographic examination of the kneejoint, but magnetic resonance imaging showed hypointensity of the distal femur. Femoral biopsy revealed proliferation of long spindle-shaped fibrosarcoma cells, while a bone marrow biopsy of iliac bone (which appeared normal on radiographic examinations) showed replacement of hematopoietic cells by fibroblast-like spindle cells. A diagnosis of multiple diffuse fibrosarcoma of bone was therefore made. Autopsy revealed tumor invasion into multiple bones and several visceral organs and extramedullary hematopoiesis in the liver, spleen and lymph nodes. As this patient had leukoerythroblastic anemia with poikilocytosis, splenomegaly exhibiting extramedullary hematopoiesis, and apparent fibrotic change in his bone marrow, we suggest that this extremely rare disease should be considered in the differential diagnosis of myelofibrosis.
Topics: Adult; Anemia, Myelophthisic; Biopsy; Bone Marrow Cells; Bone Neoplasms; Diagnosis, Differential; Fatal Outcome; Femur; Fibrosarcoma; Hematopoiesis, Extramedullary; Humans; Ilium; Magnetic Resonance Imaging; Male; Neoplasms, Multiple Primary; Primary Myelofibrosis; Tomography, X-Ray Computed
PubMed: 9652906
DOI: 10.2169/internalmedicine.37.480