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)

Normal rat kidney cells, non-productively infected with the anaemia-inducing variant of Friend spleen focus-forming virus (F-SFFVA), were metabolically labelled with [2-3H]mannose. The primary translation product of the viral envelope gene (env), representing a glycoprotein with an apparent molecular M(r) of 55,000 (gp55), was isolated from cell lysates by immunoaffinity chromatography and purified by preparative SDS/PAGE. Radiolabelled oligosaccharides, released from tryptic glycopeptides by treatment with endo-beta-N-acetylglucosaminidase H, were characterized chromatographically, by enzymic digestion and by acetolysis. The results revealed that F-SFFVA gp55 obtained from this source carried predominantly oligomannose type sugar chains with five to nine mannoses. As a characteristic feature, glycans with seven to nine mannoses contained, in part, an additional glucose residue. Although the amount of glucosylated species found was higher in F-SFFVA gp55 (about 25% of total endo-H-sensitive oligosaccharides) than in gp55 of the corresponding polycythaemia-inducing variant (F-SFFVP, 16.3%), the overall glycosylation pattern of the F-SFFVA env product closely resembled that of F-SFFVP gp55 [Strube et al. (1988) J Biol Chem 263:3762-71]. Hence, our results demonstrate that the different intracellular processing and transport of the primary F-SFFVA env product cannot be attributed to aberrant trimming of its oligomannose type glycans.
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PMID:Glycosylation of glycoprotein 55 encoded by the anaemia-inducing strain of Friend spleen focus-forming virus. 780 3

Eleven children aged 0.6-17 years with preterminal chronic renal failure and anemia (mean serum creatinine concentration 4.8 mg/dl; mean hemoglobin concentration 7.9 g/dl) were treated with sc injections of recombinant human erythropoietin (EPO, initial dose 150 U/kg/week) over a mean period of 13 months. When a target hemoglobin concentration of 11.5-13.5 g/dl was reached, the dose was adapted. Iron deficiency was corrected. Hemoglobin concentration increased by > 2 g/dl in all patients within 14-119 (mean 45) days. The last maintenance dose ranged between 75 and 300 (mean 133) U/kg/week. No major adverse effects were observed, except for hypertension which occurred in about half of the patients and necessitated interruption of EPO in one child with advanced renal failure. Additional antihypertensive drugs were given to five patients. Body height increased in two patients by 0.6 and 1.3 SDS/year, respectively. In six patients with a mean observation period of 14 months before and 16 months after the start of EPO, the mean slope of the reciprocal serum creatinine concentration curve improved slightly (p = 0.05). The proposed schedule appears to be safe for the treatment of renal anemia in most pre-dialysis patients. Frequent monitoring of hemoglobin, blood pressure, serum creatinine and ferritin is required.
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PMID:Treatment of renal anemia by subcutaneous erythropoietin in children with preterminal chronic renal failure. 811 Nov 77

Various disorders of the red cell skeleton and membrane have been described in hereditary spherocytosis. To elucidate which aberrations could be used for identification of HS patients in a Danish population, we examined ghosts from 17 HS patients and 20 normals by use of SDS-gel scanning, native spectrin extraction, and limited tryptic digestion. Compared to normals, HS patients had significantly lowered alpha-spectrin (p < 0.004), protein 4.2 (p < 0.025), and actin (p < 0.05), and significantly increased anion-transporter (p < 3 x 10(-6)) and glyceraldehyde-3-phosphate dehydrogenase (G3PD, p < 0.04). Sixteen out of 17 HS patients could be identified by aberrations of the anion-transporter or protein 4.2 outside a 95% confidence interval for normals. Extraction of native spectrin and limited tryptic digest showed no difference between normals and HS patients. RBC separated into young and old fractions were used to examine the occurrence of protein aberrations associated with RBC age. Young RBC contained more G3PD (35%) and less protein 4.1 (6.5%) and actin (8.7%) than old. In male HS patients an increased G3PD content showed a linear correlation (p < 0.001) with a low concentration of blood haemoglobin. We conclude that aberrations of G3PD, and possibly protein 4.1, and actin, are associated with anaemia in HS. Increased anion-transporter or lowered protein 4.2 may be useful for diagnosis of HS, and were inherited in five out of six families where two generations were available.
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PMID:Hereditary spherocytosis: diagnostic and anaemia-associated aberrations of ghost proteins. 819 7

The Belgrade Laboratory (b/b) rat has an autosomal mutation which in homozygous state induces severe anemia. This study was based on solubilization of total rat globin chains and their separation into alpha- and beta-globins using a 20% SDS polyacrylamide gel. These analyses demonstrated that the disbalance of alpha/beta globins in b/b red blood cells (RBC) is due to decreased level of alpha-globins. Iron-dextran administration corrected the level and globin ratio in b/b RBC thus confirming that the iron deficiency is the primary defect in b/b rats.
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PMID:The disbalance of alpha- and beta-globins in anemic Belgrade rat red blood cells. 819 63

We studied bovine subjects that exhibited a moderate uncompensated anemia with hereditary spherocytosis inherited in an autosomal incompletely dominant mode and retarded growth. Based on the results of SDS-PAGE, immunoblotting, and electron microscopic analysis by the freeze fracture method, we show here that the proband red cells lacked the band 3 protein completely. Sequence analysis of the proband band 3 cDNA and genomic DNA showed a C --> T substitution resulting in a nonsense mutation (CGA --> TGA; Arg --> Stop) at the position corresponding to codon 646 in human red cell band 3 cDNA. The proband red cells were deficient in spectrin, ankyrin, actin, and protein 4.2, resulting in a distorted and disrupted membrane skeletal network with decreased density. Therefore, the proband red cell membranes were extremely unstable and showed the loss of surface area in several distinct ways such as invagination, vesiculation, and extrusion of microvesicles, leading to the formation of spherocytes. Total deficiency of band 3 also resulted in defective Cl-/HCO3- exchange, causing mild acidosis with decreases in the HCO3- concentration and total CO2 in the proband blood. Our results demonstrate that band 3 indeed contributes to red cell membrane stability, CO2 transport, and acid-base homeostasis, but is not always essential to the survival of this mammal.
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PMID:Defective anion transport and marked spherocytosis with membrane instability caused by hereditary total deficiency of red cell band 3 in cattle due to a nonsense mutation. 862 63

We investigated the genetic defects in two patients with familial lecithin:cholesterol acyltransferase (LCAT) deficiency. Their clinical manifestations including corneal opacities, anemia, proteinuria, and hypoalphalipoproteinemia were identical for familial LCAT deficiency. Their LCAT activities and the cholesterol esterification rate (CER) were nearly zero, and their LCAT masses were below 10% of normal control values. Sequence analysis of the amplified DNA of case 1 revealed one base deletion of G at base 873 (first position of Val264) in exon 6, leading to a premature termination by frameshift. Sequence analysis of amplified DNA of case 2 revealed a single G to A converting Gly (GGT) to Ser (AGT) substitution at residue 344. When COS-1 cells were transfected with these mutants, LCAT activity in the medium was nearly zero, and the LCAT mass was undetectable (< 0.01 microgram/ml). In contrast, LCAT activity in the medium of COS-1 cells, transfected with wild-type LCAT, was 1.7 nmol/h per ml and the LCAT mass was 0.09 micrograms/ml. The LCAT mass in the cell lysates of the mutants was less than 12% of control for case 1 and 18% of control for case 2. Northern blot analysis of the mRNA of COS-1 cells transfected with the mutants showed the same amounts of LCAT mRNA as compared with wild-type LCAT. Biosynthesis of mutant LCATs was analyzed by pulse-chase and immunocytochemistry in transfected baby hamster kidney cells. SDS-PAGE/fluorography demonstrated that wild-type LCAT was synthesized as a high-mannose type of 56 kDa, which was very slowly converted to a mature form of 67 kDa and was secreted into the media. In contrast to the wild-type LCAT, the mutant precursors were not processed into the mature form but slowly degraded along with chase times. On steady and continuous labeling in the case of wild-type LCAT, the mature 67 kDa form was observed in both the cell lysate and media, whereas no mature form was detected in the cell lysates and media which were transfected mutant LCATs. These data suggest that the mutant LCATs are actually synthesized in an amount comparable to that of wild-type, but they are slowly degraded without being processed into the mature form. The immunocytochemistry revealed that mutant LCATs were mainly retained in the endoplasmic reticulum. These data suggest that these two mutations may disrupt the mutant LCATs' transport from the endoplasmic reticulum into Golgi apparatus, resulting in LCAT deficiency.
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PMID:Two novel point mutations in the lecithin:cholesterol acyltransferase (LCAT) gene resulting in LCAT deficiency: LCAT (G873 deletion) and LCAT (Gly344-->Ser). 865 71

The pathogenesis of poikilocytosis in calves was investigated. Nine calves 1 to 2 months old exhibiting poikilocytosis (poikilocytic calves), were examined. The proportion of poikilocytes in their blood was more than 70% in two calves (severely poikilocytic), while it averaged 30% in the remaining seven calves (moderately poikilocytic). All of the polikilocytic calves exhibited mild anemia. The concentration of plasma iron in 8 of them was 20-30% of that in normal calves, but it increased as the calves aged. The polikilocyte count in moderately poikilocytic calves decreased in proportion to the increase of the plasma iron concentration, though a high poikilocyte count was observed in a severely poikilocytic calf even after the plasma iron concentration reached the normal level. Column chromatography of a hemoglobin preparation from all the calves examined revealed 5 distinct peaks. Three peaks were embryonic, fetal and adult hemoglobins, respectively. The other peaks were tentatively designated Hb-2 and Hb-3, respectively. The amount of Hb-2 in the two severely poikilocytic calves was about three times that in the other calves including those moderately poikilocytic, and it decreased as the calves aged. The decrease of Hb-2 in one severely poikilocytic calf was related to a reduction of the proportion of poikilocytes in its peripheral blood. There was no significant difference in age-dependent changes of hemoglobin types between moderately poikilocytic calves and normal calves. Furthermore, SDS-PAGE analysis of red cell membrane revealed that protein 4.2 consisted of two polypeptides in the two severely poikilocytic, and three moderately poikilocytic calves, while it consisted of a single polypeptide in the remaining calves examined. These results indicated that the abnormalities of hemoglobin composition and protein 4.2 in the erythrocyte membrane observed in the severely poikilocytic calves might be responsible for the morphological changes in the erythrocytes, whereas iron deficiency was thought to be the predominant cause of poikilocytosis in the moderately poikilocytic calves.
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PMID:Hemoglobin types, erythrocyte membrane skeleton and plasma iron concentration in calves with poikilocytosis. 884 98

Rabbit ceruloplasmin (Cp) was purified after solid ammonium sulfate precipitation to 60% final saturation by a two-step column chromatography procedure, utilizing DEAE-Sephadex A-50 and changing the NaCl concentration in the buffer to 0.16 M to achieve the isolation of the protein. The purified Cp was used to prepare antibodies in guinea pigs that were used afterwards to determine the Cp concentration in normal rabbits and in rabbits with an experimentally induced chronic anemia. The molecular weight of rabbit Cp determined by SDS-PAGE was 125,000 and a high molecular weight Cp of 200,000 comprising 8% of the total purified protein was also found. An optical density ratio (610 nm/280 nm) of 0.0475 and a molar extinction coefficient of 7625 were obtained. Copper determinations yielded a value of 0.24% that corresponds to 5 copper atoms per molecule. The staining of Cp following discelectrophoresis in polyacrylamide gels also showed a two band pattern.
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PMID:Rabbit ceruloplasmin: purification and partial characterization. 895 70

Congenital dyserythropoietic anemia of type II (CDA II) is a rare disorder, usually present in childhood, with a clinical picture of chronic anemia of mild to moderate degree, splenomegaly and intermittent or persistent jaundice. It is transmitted by autosomal recessive inheritance and is characterized by the presence of a large number of multinucleate and binucleate erythroblasts in the bone marrow and typical morphological abnormalities of the membrane of circulating erythrocytes. SDS-PAGE of red blood cell membrane proteins shows a narrower aspect and a faster migration of band 3 (anion exchange transporter). This aspect is consistent with decreased glycosylation of this protein. The genetic mutations responsible for the glycosylation defect in CDA II have not yet been identified. Analysis of carbohydrate structures and biochemical data indicate that the activity of either GnT II or alpha-Man II is reduced in different families, suggesting that the disease is genetically heterogeneous. Molecular cloning of the GnT II and alpha-Man II DNA sequences has allowed direct investigation of the genetic mutations underlying the glycosylation defect in CDA II patients to begin.
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PMID:Congenital dyserythropoietic anemia type II: molecular basis and clinical aspects. 900 44

Antisera raised against oriented peptide conjugates were used to identify and partially characterize a 24 kDa protein product expressed by chicken anaemia virus (CAV). The peptides derived from the N and C termini of the protein were shown to react against the native protein, expressed within virus-infected cells, by immunofluorescence, immunoperoxidase and immunogold thin section electron microscopy techniques. The protein product was located by immunogold single labelling in intranuclear inclusions similar to those described previously for the 13 kDa CAV protein, which causes apoptosis. The 24 kDa protein was co-localized to the nuclear inclusions with the CAV 13 kDa protein by simultaneous dual labelling immunogold electron microscopy. Following isolation of the CAV proteins by nuclei isolation and SDS-PAGE, the antisera were used to probe for the protein by immunoblotting. The antisera recognized an expressed protein product of apparent molecular mass 30 kDa. An immunofluorescence time course study of CAV protein expression was carried out and the peptide antisera reacted against the protein at 12 h post-infection. Antisera against the 13 kDa protein reacted at similar times post-infection. This was in contrast to antisera raised against the 52 kDa capsid protein which is detectable by immunofluorescence only after 24 h. The 13 kDa and 24 kDa proteins thus appear to be early antigens produced by CAV during infection.
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PMID:Identification of a 24 kDa protein expressed by chicken anaemia virus. 904 62


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