Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002895 (sickle cell disease)
 11,747 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Red cell survival was measured in ten subjects with S-C disease and one with S-O Arab (alpha 2 beta 2-121 glu yields lys) disease using both DF32p and 51Cr as tags. Red cell volume was slightly reduced in most patients (87% plus or minus 20% of predicted normal). In nine SC patients, mean red cell life (DF32p) was 28.9 plus or minus 4.0 days. For one SC subject it was significantly longer (47.9 days), as it was for the one with S-O Arab. The S-O Arab subject had irreversibly sickled cells in the peripheral blood, shereas those with SC had few (less than 1/1000 red cells) or none. The S-O Arab hemolysate gelled at a hemmoglobin concentration (16.2 g/100ml) near that for sickle cell anemia hemolysates (15.9 plus or minus 1.0 g/100 ml; n equals 8) but significantly lower than that for SC hemolysates (21.6 plus or minus 1.9 g/100 ml; n equals 5). It seems likely that properties of S-C red cells other than their relative ease of sickling contribute significantly to their rate of hemolysis.
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PMID:Red cell life span in sickle cell-hemoglobin C disease with a note about sickle cell-hemoglobin O ARAB. 112 Jan 86

The most common method of blood sample collection for neonatal screening programs for inherited diseases-blood spots on filter paper--is poorly suited for screening of sickle cell diseases by conventional assays because of the denaturing effects of this medium on hemoglobins that affect their electrophoretic identifications. The monoclonal antibody beta (6)-1 specifically recognizes the hemoglobin A beta-chain residue 6 (glutamic acid), that is, the normal counterpart of hemoglobins S and C, and this recognition is unaffected by changes in hemoglobins induced by filter paper storage. The beta (6)-1 immunoassay analysis of 67 prescreened samples extracted from filter paper permitted unambiguous group identification, by virtue of nonreactivity, of the pathologic sickle cell disease phenotypes SS (sickle cell anemia) and SC (sickle cell-hemoglobin C disease), along with the homozygous hemoglobin C phenotype (hemoglobin CC disease). Other phenotypes identified by beta (6)-1 nonreactivity would include S-beta(0) thalassemia, C-beta (0) thalassemia, and beta(0) thalassemia (Cooley's anemia). As systems for collecting newborn blood specimens on filter paper and their transmittal to centralized laboratories are already established in many states, this assay for sickle cell and hemoglobin C diseases could rapidly be combined with other mass screening programs for inborn errors of metabolism.
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PMID:Negative screening for sickle cell diseases with a monoclonal immunoassay on newborn blood eluted from filter paper. 224 58

The UP1 single-stranded nucleic acid binding protein from calf thymus (Herrick, G. & Alberts, B.M. (1976) J. Biol. Chem. 251, 2124-2132) has recently been shown to be a proteolytic fragment derived from the A1 heterogeneous nuclear ribonucleoprotein (hnRNP) (Pandolfo et al. (1985) Nucleic Acids Res. 13, 6577-6590). The NH2-terminus of the 22,162 dalton UP1 protein appears to be blocked, which suggests that UP1 represents the NH2-terminal two thirds of this 32,000 dalton hnRNP protein. The complete amino acid sequence for UP1 was derived from automated sequencing of peptides that were purified by HPLC from digests with trypsin, chymotrypsin, Staphylococcus aureus protease, endoproteinase Lys-C, and cyanogen bromide. Trichloroacetic acid precipitation followed by enzymatic digestion in 2 M urea proved to be the best approach for generating UP1 peptides. By carboxymethylating after, rather than before, digestion it was possible to avoid problems associated with the insolubility of the carboxymethylated UP1. All of the resulting peptides in amounts varying from 2 to 15 nmol were coupled to aminopolystyrene prior to solid-phase sequencing. Using these methods, no difficulties were encountered in assigning glutamic acid residues or in completely sequencing peptides that contained up to 25-30 residues. The relative ease with which the UP1 protein was sequenced, requiring only about a year to complete, and the comparatively modest amount of protein required, less than 5 mg, attests to the usefulness of water soluble carbodiimide coupling and solid-phase sequencing for determining the primary structures of proteins. In addition to serving as a basis for determining structural relationships among various mammalian single-stranded nucleic acid binding proteins, the amino acid sequence of UP1 reveals that the A1 hnRNP protein contains a region of internal sequence homology that apparently corresponds to two independent nucleic acid binding sites.
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PMID:Amino acid sequence of UP1, an hnRNP-derived single-stranded nucleic acid binding protein from calf thymus. 303 34

Direct analysis of fetal DNA using restriction endonucleases constitutes a major area of progress in prenatal diagnosis. This recent technology may permit the precise identification of a mutant allele for some diseases, whereas in others it allows the familial segregation of a pathogenic allele to be followed by its linkage to a DNA sequence polymorphism. This type of analysis, available in a few centers, is currently used, among others, for the prenatal diagnosis of hemoglobinopathies such as sickle cell anemia. After fetal cells have been obtained by choriocentesis or amniocentesis, the extracted DNA is exposed to selected restriction enzymes. In the diagnosis of sickle cell anemia the mutant codon responsible for the substitution of glutamic acid by valine in the beta hemoglobin chain is no longer cut by the enzyme Mst II, due to its variance with the normal codon; this difference in fragment length is detected by DNA electrophoresis, and the particular fragments are identified by molecular hybridization with appropriate radioactive probes. Utilizing these methods the genotype of a homozygous normal fetus can be distinguished from that of a homozygote affected or a heterozygote for the sickle mutation of the beta hemoglobin chain. We have recently applied this prenatal methodology to the pregnancies of two couples from Zaire, in which each member was a proven sickle cell carrier. Fetal material was obtained in both cases by amniocentesis at the 16th week of gestation and followed by cell culture. In the first case, a 46, XX fetus, DNA (10 mcg) revealed a heterozygous sickle cell carrier genotype.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Prenatal prevention of drepanocytosis: analysis of cellular DNA in 2 cases]. 402 Mar 52

Two human hemoglobins designed to inhibit the polymerization of sickle hemoglobin (Hb S; alpha 2 beta S2) have been produced. Mutations that disrupt the ability of Hb S to form polymers were introduced into the normal human beta-globin gene by site-specific mutagenesis. These mutations affect the axial and lateral contacts in the sickle fiber. The recombinant hemoglobin designated anti-sickling hemoglobin 1 (Hb AS1) contains the mutations beta 22 glutamic acid to alanine and beta 80 asparagine to lysine. Hb AS2 has the same beta 22 glutamic acid to alanine mutation combined with beta 87 threonine to glutamine. Human alpha- and beta AS-globin genes were separately fused downstream of beta-globin locus control region sequences and these constructs were coinjected into fertilized mouse eggs. Transgenic mouse lines that synthesize high levels of each anti-sickling hemoglobin were established and anti-sickling hemoglobins were purified from hemolysates and characterized. Both AS hemoglobins bind oxygen cooperatively and the oxygen affinities of these molecules are in the normal range. Delay time experiments demonstrate that Hb AS2 is a potent inhibitor of Hb S polymerization; therefore, locus control region beta AS2-globin gene constructs may be suitable for future gene therapy of sickle cell disease.
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PMID:Recombinant human hemoglobins designed for gene therapy of sickle cell disease. 793 4

Neonates with sickle cell disease (SCD) are of normal size at birth in terms of height and weight. However, by the sixth month of life their growth begins to lag significantly behind that of non-sicklers. We hypothesize that such growth retardation could be explained, at least in part, by the increased excretion of free amino acids in the urine of children with SCD. It is well established that in SCD there are abnormalities in the proximal tubules where amino acids are reabsorbed. We collected serum and urine samples from 13 patients with SCD (age range, 10 months to 14 years), and 17 age-and gender-matched controls, and analysed these specimens for free amino acids and creatinine. The SCD population was less well nourished than the controls, as evidenced by the lower serum prealbumin levels in the former group (91.3 v. 127 mg/l, P = 0.01). The serum concentrations of all of the essential amino acids were significantly reduced (21-47 per cent, P < 0.01) in the SCD subjects, as were those of most of the non-essential amino acids (exceptions: alanine, glutamic acid, proline). The urine concentrations of seven of the essential amino acids (indexed to creatinine) were increased in the SCD children. The greatest difference in urinary amino acid excretion was seen with methionine; the SCD subjects excreted 3.6-fold more methionine than the controls. These data indicate that reduced levels of serum amino acids resulting from increased urinary loss of these amino acids in children with SCD could contribute to the decreased growth rates one sees in children with this genetically inherited hematologic disorder.
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PMID:Serum and urinary amino acid levels in sickle cell disease. 928 25

Sickle cell anemia is a genetic blood disorder arising from a point mutation in the beta-globin gene that leads to the replacement of glutamic acid residue by valine at the sixth position of the beta--chain of hemoglobin. At low oxygen tension, the mutant hemoglobin, sickle hemoglobin, polymerizes inside the red blood cells into a gel or further into fibers leading to a drastic decrease in the red cell deformability. As a result, micro-vascular occlusion arises which may lead to serious, sometimes fatal, crises. The present article reviews the historical, genetic, molecular, cellular, and clinical aspects of the disease. A review for the development and design of drugs to treat sickle cell anemia is presented. Anti-sickling agents are classified, based on the target to be modified, into three classes: the gene, the sickle hemoglobin molecule, and the red cell membrane modifiers. In spite of the full understanding of the pathology, physiology, and the molecular nature of the disease, and the development of large number of antisickling agents, a cure for sickle cell anemia still is unavailable. Strategies to treat sickle cell anemia since the early times of the disease state discovery in 1910, has focussed mainly on prophylactic measures to alleviate the painful crises. The article addresses clinical approaches used then and now to treat the disease, and the rationale of their use. Currently in clinical practice, hydroxyurea is the most commonly used agent to treat the disease, and it has been recently approved by the united states Food and Drug Administration as a drug for that purpose.
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PMID:Sickle cell anemia and antisickling agents then and now. 1117 67

The substitution of glutamic acid by valine at the sixth position of the beta-globins of haemoglobin S (Hb S) causes a drastic reduction in the solubility of the deoxy form of Hb S. Under hypoxic conditions, deoxy-Hb S molecules polymerize inside the cells, forming rigid, sickled cells. We studied the effect of Niprisan (Nix-0699), a naturally occurring antisickling agent, on the survival of transgenic (Tg) sickle mice under severe acute hypoxic conditions (60 min). Before hypoxia exposure, the mice were treated by gavage once daily for 7 d with 0 mg/kg (n = 10), 10 mg/kg (n = 5), 50 mg/kg (n = 5), 300 mg/kg (n = 4) or 500 mg/kg (n = 5) of Nix-0699. The mean survival times of the untreated and treated mice were 10, 25, 39, 55 or 60 min respectively. The percentage of sickled cells in the venous blood of the treated mice was lower than that in control mice and was dose dependent. Histological examination of the lungs of the control mice showed entrapment of massive numbers of sickled cells in the alveolar capillaries, although the degree of such entrapment decreased with the increased dose of Nix-0699. Nix-0699 may be a promising option for the treatment and management of patients with sickle cell disease.
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PMID:Niprisan (Nix-0699) improves the survival rates of transgenic sickle cell mice under acute severe hypoxic conditions. 1295 72

Sickle hemoglobin is a mutant hemoglobin in which valine has been substituted for the glutamic acid normally at the sixth amino acid of the beta-globin chain. Detection of the single base pair mutation at codon 6 of the beta-globin gene is important for the prenatal diagnosis of sickle cell anemia and sickle cell disease. Application of the polymerase chain reaction technology to detect sickle cell patients and heterozygous carriers in a group of patients suspected for sickle cell disease was carried out. The sample was composed of 52 normal individuals and 52 unrelated outpatients who were attending the Hematology Research Center. All patients were interviewed. Results of their medical histories, physical examination, and the hematological analysis were recorded. The blood samples were collected in EDTA and genomic DNA was extracted from leukocytes. An amplified 110 base pair fragment of the beta-globin gene containing codon 6, was digested with the restriction enzyme MS II, and electerophoresed in 3 per cent agarose. We have established the technical condition for detection of sickle cell disease using a PCR assay. Fifteen patients having haemoglobin (Hb SS) and 37 patients in the heterozygous state (Hb AS) were identified. We confirm that the normal controls have the Hb AA genotype. The standardization of a highly sensitive and specific diagnostic test for sickle cell disease permitted us to identify the normal controls, the homozygotes and heterozygotes. This amplification method is rapid, sensitive and simple, and also has application research that is important for the prenatal diagnosis of sickle cell disease.
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PMID:Molecular analysis of Iranian families with sickle cell disease. 1583 69

Sickle-cell anemia is a genetic blood disease characterized by a hemoglobin gene mutation. The genetic failure is basically constituted by replacement of the hemoglobin beta chain in the sixth position so that the amino acid valine is encoded instead of glutamic acid. As a result, the erythrocytes have their normal biconcave discoid shape distorted, generally presenting a sicklelike shape, which reduces both their plasticity and lifetime. Because a complete blood supply is so important during application of both intraoral and extraoral forces, this article addresses the general and oral aspects associated with sickle-cell anemia. This will guide the clinician regarding such patients who seek orthodontic treatment by making references to literature on multidisciplinary management.
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PMID:Orthodontic treatment of patients with sickle-cell anemia. 1653 52


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