Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002871 (anemia)
 52,094 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The preimplantation diagnosis of a HbSA-globin transgene in biopsied trophectoderm cells and blastomeres in embryos using a transgenic mouse model for the trait of human sickle-cell anaemia has been undertaken. A sensitive procedure was developed for the amplification of the human beta-globin gene sequence flanking the sickle mutation. Polymerase chain reaction (PCR) assays were undertaken on one to five biopsied trophectoderm cells and isolated blastomeres of the preimplantation mouse embryo. After biopsy the blastocysts were cultured whilst the cells were analysed for the presence of the transgene, and a high proportion (82-91%) were viable as assessed by the presence of a blastocoele cavity within a 5-h period. The majority of the biopsied cultured blastocysts were frozen and used to confirm the diagnosis; 90 biopsied cultured blastocysts were transferred to pseudopregnant recipients and 34% established pregnancy. Material from day 13.5 post-coitum fetuses was also used to confirm the original diagnosis. The time (4-5 h) required to carry out the analysis obviates a need for extended culture or cryopreservation of the biopsied embryo. In individual experiments under optimal conditions, the presence of the transgene in biopsied cells was detected with 100% accuracy, and the PCR analysis was sensitive at the 1-cell level. The overall success rate of diagnosis and confirmation of the presence or absence of the human beta-globin sequence in the biopsied embryo was 70%. Over the entire experimental period (14 months) DNA contamination from a variety of sources did occasionally occur; the methods used to overcome this problem are discussed.
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PMID:Preimplantation diagnosis of a human beta-globin transgene in biopsied trophectoderm cells and blastomeres of the mouse embryo. 136 3

Fanconi anemia (FA) is a rare genetic disorder characterized by progressive pancytopenia, congenital abnormalities, and a predisposition to malignancy. Recently, mutation in a novel gene named FACC (Fanconi anemia C complementing) has been identified as causing one type of FA. Here, we report successful functional complementation of four FA(C) cell lines using a retroviral vector to transfer a copy of the normal FACC gene. The hallmark of the FA cell phenotype is extreme sensitivity to cross-linking agents such as mitomycin C (MMC). Cell lines transduced by FACC viral vectors were distinguished by their ability to grow at concentrations of MMC several orders of magnitude higher than those concentrations inhibitory of parental controls. The genetically corrected cell lines were analyzed for susceptibility to MMC-induced chromosomal breakage and were found to have been normalized. These two different assays confirmed that our retroviral vectors were capable of transferring a functional FACC gene to lymphoid cell lines established from FA(C) patients. We next analyzed the ability of our viral vectors to functionally correct hematopoietic progenitor cells from a patient bearing a splice donor mutation. Progenitor cells were purified by an immunoaffinity column to enrich for cells with high CD34 expression. Similar to FA lymphoid cell lines, this patient's CD34-enriched cells were extremely sensitive to MMC. After infection of these progenitor cells with viral vectors bearing normal FACC, increased numbers of colonies formed both in the absence and presence of < or = 5 nmol/L MMC, but no colonies formed from uninfected cells, even in the absence of MMC. Polymerase chain amplification was used to confirm proviral DNA integration. Thus, retroviral vectors can be engineered to transfer a normal FACC gene to lymphoid cell lines and primary hematopoietic cells bearing four different FACC mutations. FA stem cells rescued by gene transduction should have a selective growth advantage within the hypoplastic FA marrow environment in vivo. These experiments suggest that gene therapy may be an effective treatment strategy for FA.
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PMID:A functionally active retrovirus vector for gene therapy in Fanconi anemia group C. 751 16

Fever, loss of weight, anaemia, hepatosplenomegaly and lymphadenopathy developed in two HIV-infected patients. At first malignant lymphoma with septicaemia was thought to be the cause. In both patients Salmonella enteritidis was isolated by blood culture and found to be sensitive against the antibiotics that were given (5 g azlocillin and 2 g cefotaxime, three times daily each; additionally in case 2, metronidazole, 500 mg three times daily). Because bone-marrow biopsy demonstrated acid-fast rods, antimycobacterial treatment was started (isoniazid 300 mg/d, rifampicin 600 mg/d, ethambutol 1,200 mg/d and pyrazinamide 2 g/d). Despite this the patients died of septic shock. Histological examination revealed massive amounts of acid-fast rods in spleen, liver, gut and bone marrow. Polymerase chain reaction and sequencing identified the structure as that of the recently discovered M. genavense.
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PMID:[Mycobacterium genavense infection in AIDS]. 844 11

The relationship between transient erythroblastopenia of childhood (TEC) and parvovirus B19 infection remains uncertain. Large series using primarily serologic evaluation have not shown an association, whereas smaller series have reported parvovirus B19 infection in such patients. Further, parvovirus DNA or antigen has been detected in some patients seronegative for the virus at presentation. Polymerase chain reaction (PCR) amplification has never been used to evaluate patients with TEC for parvovirus B19. We used the PCR in an attempt to detect parvovirus B19 in DNA extracted from archived bone marrow coverslips of 16 patients diagnosed with TEC. The patients ranged in age from 3 to 23 months and presented with a mean hemoglobin value of 5.4 g/dL. Sixty-nine percent were neutropenic and none was thrombocytopenic. None of the patients had histologic evidence of parvovirus B19 infection in the bone marrow. DNA amplification for parvovirus B19 was negative in each case. In contrast, parvovirus B19DNA was amplified from DNA isolated from archived bone marrow coverslips of a patient with known parvovirus B19 infection, indicating that the PCR assay was sufficiently sensitive to detect virus from archieved bone marrow coverslips. Review of the literature indicates that the patients with parvovirus-associated TEC are generally older and often present with concomitant thrombocytopenia, whereas patients with parvovirus B19-negative TEC are younger and present without thrombocytopenia, similar to the patients in our study. Our results suggest that parvovirus B19 is not the cause of anemia in the young patient with typical features of TEC. Rather, parvovirus B19 infection of older, previously healthy children may occasionally cause a protracted anemia, often with thrombocytopenia, which may be diagnosed by some as TEC.
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PMID:Polymerase chain reaction amplification of archival material for parvovirus B19 in children with transient erythroblastopenia of childhood. 902 46

A 12-year-old boy was referred because of abdominal pain, gross hematuria, and passage of stones. Further evaluation showed growth delay, low average range of intellectual functioning, and a speech articulation disorder. No signs of self-mutilation or self-injurious behavior were present. He had hyperuricemia, hyperuricosuria, uric acid crystalluria, uric acid calculi, macrocytosis, megaloblastic bone marrow changes, and mild anemia. Hypoxanthine phosphoribosyltransferase (HPRT) enzyme activity was reduced to approximately 26% of normal. Polymerase chain reaction-single strand conformational polymorphism analysis of the HPRT gene in DNA isolated from the patient's blood lymphocytes revealed a single nucleotide substitution at codon 200 in exon 8. The base change was a guanine to cytosine transversion, resulting in the conservative amino acid substitution of threonine in place of arginine. To our knowledge, this mutation has not previously been reported.
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PMID:A new point mutation in a hypoxanthine phosphoribosyltransferase-deficient patient. 932 99

Medical records of 3 dogs from North Carolina and 3 dogs from Virginia with ehrlichial morulae in circulating neutrophils were studied retrospectively. Two clinically distinct disease syndromes, including chronic, moderate to severe anemia (n = 3) and polyarthritis (n = 2) were associated with canine granulocytic ehrlichiosis (CGE) in these dogs. One dog was clinically healthy, and abnormalities were not detected during physical examination. Clinical signs were nonspecific and included fever, lethargy, anorexia, vomiting, and diarrhea. The most frequent laboratory abnormalities were normocytic normochromic nonregenerative anemia, moderate thrombocytopenia with large platelets, lymphopenia, and eosinopenia. Considerable variability was found in the serologic responses to Ehrlichia equi, Ehrlichia canis, and Ehrlichia chaffeensis antigens among the 5 dogs for which stored sera were available for indirect fluorescent antibody testing. Polymerase chain reaction amplification and sequencing of portions of the 16S rRNA gene from blood (collected in ethylenediaminetetraacetic acid) of 1 severely anemic dog (dog 3) and 1 polyarthritic dog (dog 4) resulted in DNA sequences nearly identical to the GenBank accessions for Ehrlichia ewingii. The DNA sequence from a 3rd dog (dog 5) was most similar to that of E. canis. Serologic or molecular results support the possibility of E. ewingii, E. equi, and E. canis coinfection or serologic cross-reactivity among canine granulocytic and monocytic Ehrlichia species in dogs from North Carolina and Virginia. Variability in response to tetracycline or doxycycline treatment was noted in these dogs, with more rapid resolution of signs in dogs with polyarthritis. We report the 1st cases of CGE in dogs from North Carolina and Virginia, including recognition of CGE in a healthy dog.
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PMID:Granulocytic ehrlichiosis in dogs from North Carolina and Virginia. 956 Jul 60

The proliferative and differentiative response of neutrophils to granulocyte-macrophage colony-stimulating factor (GM-CSF) is known to be impaired in patients with myelodysplastic syndromes (MDS). To investigate the mechanisms of the defective response in MDS, we examined expression levels of GM-CSF receptor alpha (GMR alpha) and common beta (beta c) subunits on CD16(+) neutrophils, CD14(+) monocytes and CD3(+) T cells from 26 MDS patients and 10 healthy controls using flow cytometry. Expression of GMR alpha was significantly decreased on the neutrophils of five out of 26 patients and was not specific for any FAB subtype. In contrast, beta c expression on neutrophils was significantly reduced in 14 out of 26 patients with a higher proportion occurring in the advanced stages of MDS including refractory anaemia with excess of blasts (RAEB), RAEB in transformation (RAEBt) and overt leukaemia compared with refractory anaemia (RA)/RA with ringed sideroblasts (RARS) or healthy controls. Decreased beta c also correlated with the degree of hypogranular neutrophil morphology and increased infection. Expression of both subunits on T cells and monocytes in MDS was similar to normal controls. Polymerase chain reaction amplification of reverse-transcribed mRNA isolated from the affected neutrophils suggests that the reduction of beta c may result from decreased message levels. The observed reduction in GM-CSF receptor expression could account for the impaired proliferative and maturational responses in MDS.
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PMID:Neutrophil-specific reduction in the expression of granulocyte--macrophage colony-stimulating factor receptor subunits in myelodysplastic syndromes. 1112 48

This article is the first report of hemoglobin (Hb) Pyrgos along with other Hbs forming triple-heterozvgous patterns. Of 2 cases, the first occurred in a Thai girl with thalassemic facies, marked anemia, and hepatosplenomegaly, who had Hb Pyrgos in association with Hb H disease with Hb Constant Spring (CS). This case represents a triple heterozygosity comprising Hb Pyrgos, alpha-thalassemia 1, and Hb CS. Hb electrophoresis revealed an abnormal Hb in addition to Hbs CS, A2, A, Bart's, and H. This abnormal Hb moved slightly faster than Hb A but more slowly than Hb Bart's. Polymerase chain reaction revealed that the abnormal Hb was caused by a missense mutation within codon 83 of the beta-globin gene (GGC to GAC) resulting in a glycine-to-aspartic acid substitution, which corresponds to Hb Pyrgos. The patient required blood transfusions by the age of 3 years. A splenectomy was performed when she was 5 years old, after which her hematocrit level remained above 32%. The second case was the patient's older sister who was also triple heterozygous (Hb Pyrgos, E, and CS) but was healthy.
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PMID:Triple heterozygosity of a hemoglobin variant: hemoglobin Pyrgos with other hemoglobinopathies. 1184 88

Traditionally, the treatment of viral hepatitis C (positive Polymerase Chain Reaction -PCR-) was with Interferon. A combination of Interferon plus Ribavirin has been producing better results in last years. Currently, Ribavirin is not indicated for patients with Chronic Kidney Disease because of a high risk of severe anaemia. In a few cases, this treatment is producing good results with previous dose adjustment. We show a case of a 28-year-old man with Chronic Kidney Disease on treatment with periodical hemodialysis and chronic hepatopathy HCV Positive RNA HCV (> 1,000,000 copies/ml) and persistent transaminase elevation. Before kidney transplantation, we decided to use Interferon (3,000,000 IU/48 hours) and Ribavirin (200 mg/24 hours) treatment. After 15 days, we saw normal transaminase values and HCV RNA was negative. The patient required temporary suspension of Ribavirin and two red blood cell transfusions due to severe anaemia. Ribavirin was reintroduced 200 mg/48 h posthemodialysis. The patient did not present any complication again, and could be treated for 14 months. After next 11 months of evolution the patient has normal rates of liver function and negative HCV RNA values.
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PMID:[Therapy with interferon plus ribavirin in hemodialysis patient with PCR-positive viral hepatitis C]. 1521 67

Neurologic disease occurs sporadically in horses infected with the equine infectious anemia virus (EIAV). This report describes a case of clinically severe neurologic disease in a pony experimentally infected with EIAV. This pony did not have fever or anemia, which are the characteristic clinical signs of disease. The histopathologic changes were characterized as lymphohistiocytic periventricular leukoencephalitis. Polymerase chain reaction and in situ hybridization data showed that the brain lesions were directly associated with viral replication and that high-level viral replication occurred selectively within the lesion and not in other tissues. These findings suggest that EIAV-associated neurologic disease is the direct result of viral replication.
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PMID:Leukoencephalitis associated with selective viral replication in the brain of a pony with experimental chronic equine infectious anemia virus infection. 1534 29


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