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)

The kinetic inhibition of the gelation of hemoglobin S is compared to the change in hemoglobin S soulbility, when the solubility is altered by carbon monoxide, pH, or urea. By means of a new technique, the delay time and the extent of gelation are measured on the same sample. They delay time, td, is found to be proportional to a high power (30-40) of the hemoglobin S solubility. Togehter with the previously reported concentration dependence, this result demonstrates that the rate is proportional to a high power of the supersaturation, S, defined as the ratio of the total hemoglobin S concentration to the equilibrium solubility. The results obey the supersaturation equation td-1 = gammaSn, where gamma is an empirical constant (about 10(-7) sec-1) and n is about 35. The supersaturation equation can successfully account for observations on the kinetics of cell sickling and is therefore used to estimate the increase in the delay time for sickling necessary to produce significant clinical benefit to patients with sickle cell disease.
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PMID:Supersaturation in sickle cell hemoglobin solutions. 0 40

A method is described wherein blood samples taken from adults or newborns and dried on filter paper can be used for hemoglobin analysis within 2 years after sampling. The samples are eluted in 8 M urea in the presence of 5% 2-mercaptoethanol and 2% of the neutral detergent Nonidet P-40. Then the individual alpha, beta, gamma, and epsilon chains are separated by means of electrofocusing in 8 M urea-PAA gels. Up to 96 samples can be applied to a gel using multiple syringes. Several hundred samples can be analyzed daily by one person. This method may be especially useful for preventive programs against sickle cell anemia as well as for human mutation monitoring systems.
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PMID:Improved screening test for abnormal hemoglobins from dried blood samples. 53 5

Serums from 4 species of deer and 1 species of antelope were analyzed for various components in order to define an animal disease model for sickle cell disease in people. Animal species included black-tailed deer (Odocoileus hemionus columbianus), mule deer (Odocoileus hemionus), sika deer (Cervus nippon nippon), fallow deer (Dama dama), and pronghorn antelope (Antilocapra americana). The mean serum values for total bilirubin, total protein, albumin, creatinine, urea nitrogen, and electrolytes were similar in all species and were in the normal range for human beings. Cholesterol and uric acid values for all animals were lower than those for people. Alkaline phosphatase values in the 4 cervid species were higher than in the pronghorn antelope. Values for glutamic oxalacetic transaminase were lower in the cervids than in the pronghorn antelope. Lactic dehydrogenase values were similar in the 5 species. High activities for glutamic oxalacetic transaminase and lactic dehydrogenase in the 5 species probably related to muscle mass and great muscular activity.
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PMID:Serum biochemical and electrophoretic values from four deer species and from pronghorn antelope. 119 May 86

The effect of urea on the oxygen affinity of sickle cells and normal cells was studied up to a concentration of about 1.0 M. Besides the increase in oxygen affinity found in both normal and sickle cells there was a further increase found only in the sickle cells. This specific increase was caused by the direct inhibition of the polymerization of deoxygenated Hb-S by the urea and was used to measure the extent of this inhibition. Even at concentrations of 1.0 M the urea did not fully inhibit the polymerization. At the urea concentrations recommended for treatment of sickle cell crises and for the oral treatment of the disease there was only a very slight inhibition of polymerization. The small increase in oxygen affinity brought about by these concentrations of urea (equivalent to a log P50 change of 0.016) will cause some additional minimal inhibition of sickling at physiological partial pressures of oxygen. Oxygen dissociation measurements of Hb-A in dilute solution showed that 0.95 M urea had no effect on the interaction of 2,3-DPG and chloride with haemoglobin nor on the haem-haem interactions. This implies that the quaternary 'deoxy' form of the haemoglobin may still form and that the action of urea in inhibiting the polymerization is through interference with the intermolecular bonds rather than by inducing a conformational change which disrupts the bonding. Unless urea at the concentrations recommended for treatment inhibits the sickling of the cells by some mechanism other than its effect on the haemoglobin (such as by an effect on the membrane), these results suggest that it is of little use for the treatment of sickle cell disease.
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PMID:The effect of urea on sickling. 119 70

Sickling, viscosity and gelling properties of the red cells and the hemoglobins of three Virginia white-tailed deer homozygous for types II and III (the sickling types) and V (the nonsickling type), respectively, have been analyzed. The sickling of erythrocytes of deer with type II or III is inhibited by urea and cyanate at concentrations which are comparable to those used in in vitro studies of red cells from patients with sickle cell anemia. No differences were observed between the viscosities of the three deer hemoglobin types at temperatures of 12 degrees C or above. High concentrations of deer hemoglobin types II and III gelled at 1 degree C and at pH values of 7.4-7.7; the minimum gelling concentration of type II was 33.5 g% and of type III was 38 g%. Gel formation was not observed at pH values between 6.7-7.1. Hemoglobin type V did not gel and prevented the formation of gels of type II and III in mixtures at pH 7.6-7.7.
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PMID:Viscosity and gelation studies in deer hunting hemoglobins. 120 78

Urea kinetics were measured on two separate occasions in five adults with normal haemoglobin genotype (HbAA) and in four who were homozygous for sickle cell disease (HbSS). Prime/intermittent doses of [15N15N]urea were given orally on one occasion and intravenously on the other. In three of the nine individuals there appeared to be significant hydrolysis of the oral dose of urea before absorption, leading to spurious results for the urea kinetics. When only the studies in which isotope was given intravenously were considered, there was a difference in the rate at which urea-N was salvaged, with more urea-N being salvaged by HbSS subjects than HbAA. It is concluded that the oral presentation of isotope can be used to measure urea kinetics provided care is taken to exclude those subjects who are likely to display upper intestinal hydrolysis, and that there are differences in aspects of urea kinetics between HbAA and HbSS which may be of metabolic importance.
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PMID:Urea kinetics: comparison of oral and intravenous dose regimens. 163 48

To study the potential of multivariate classification methods in order to obtain more insight into abnormal laboratory data from patients with sickle cell disease, we investigated standard haematological and clinical chemical variables of 18 controls and 37 apparently healthy persons with heterozygous sickle cell disease (Hb AS), all women, using both univariate and multivariate classification methods. In the univariate method, those with Hb AS showed decreased serum log aspartate aminotransferase (log AST) activity, mean corpuscular volume and mean corpuscular haemoglobin (MCH) and increased sodium concentration. The multivariate method identified sodium, potassium, urea, uric acid, log AST, alanine aminotransferase and MCH as the variables that produced maximal separation between persons with Hb As and controls. It increased the 'non-error rate' for classification of persons with Hb AS by 16.4% compared with classification based on the variable, MCH, that produced maximal separation by the univariate method. The frequency distribution of percentage Hb S in the Hb AS group proved bimodal with maximal separation at 37.0% Hb S. The subgroup with 37.0% or less (n = 16) was considered to have concomitant heterozygous alpha-thalassaemia-2. In the univariate method the subgroup characterized by greater than 37.0% Hb S (n = 21) had increased serum sodium and uric acid concentrations, perhaps related to sickle cell nephropathy, whereas the subgroup with less than or equal to 37% Hb S did not. The multivariate method added information to the univariate method by additionally identifying abnormalities in serum potassium and urea concentrations in the former subgroup.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Potential of descriptive linear discriminant analysis for studying clinical chemical and haematological data from persons with heterozygous sickle cell disease. 189 49

The influence of the alpha-thalassaemia gene on the haematological, biochemical and clinical presentation of sickle cell anaemia (SCA) was investigated in Saudi patients with 1 or 2 alpha-gene deletions. The results were compared to the results obtained in SCA patients without alpha-thalassaemia. In SCA patients with 2 gene deletions (homozygous alpha-thalassaemia 2), the mean cell volume, mean cell haemoglobin and Hb F were significantly lower (p less than 0.05), while packed cell volume and Hb A2 level were considerably higher (p less than 0.05) than in the SCA patients without alpha-thalassaemia. RBC and haemoglobin were higher in the former group, but the difference was not statistically significant. Patients with 1 gene deletion had intermediate values. Among the biochemical parameters, the bilirubin level was highest in patients with 1 gene deletion. Triglyceride, cholesterol, creatinine and urea levels were lower in all SCA patients, while alkaline phosphatase (ALP) and transaminases were elevated. The increase in the levels of ALP, SGOT and SGPT was maximum in the SCA patients with 2 gene deletions, but except for SGOT, the increase was not statistically significant. The retrospective analysis of the clinical data revealed that SCA patients with alpha-thalassaemia had fewer complications and had received fewer blood transfusions than the patients without alpha-thalassaemia.
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PMID:Clinical manifestation and laboratory findings of sickle cell anaemia in association with alpha-thalassaemia in Saudi Arabia. 242 Jan 34

The chemistry, pharmacology, pharmacokinetics, clinical uses and efficacy, adverse effects, drug interactions, dosage and administration, and formulary considerations of epoetin are described. Erythropoietin, a glycoprotein hormone primarily synthesized in the kidney, is the chief regulator of red blood cell production. Erythropoietin concentrations increase in response to a hypoxic state, resulting in increased red blood cell formation, accelerated hemoglobin production, and premature movement of reticulocytes into the circulation. The human gene responsible for the production of erythropoietin recently was cloned, and the recombinant product--epoetin--has been made available through mass production. The apparent volume of distribution of i.v. epoetin approximates the assumed plasma volume both in healthy volunteers and in patients with chronic renal failure. Little is known about the metabolism and route of elimination of epoetin and erythropoietin. Epoetin recently was approved by the FDA for treatment of anemia associated with chronic renal failure. Clinical trials in patients receiving hemodialysis or peritoneal dialysis and in predialysis patients with renal dysfunction demonstrate epoetin's efficacy. Other potential indications include augmentation of blood production in patients enrolled in autologous blood donation programs and treatment of anemias associated with rheumatoid arthritis, sickle cell disease, acquired immunodeficiency syndrome, cancer, and premature birth. The most frequent adverse effect associated with epoetin therapy is the worsening or development of hypertension. Other adverse effects include thrombocytosis, hyperkalemia, rise in serum urea concentration, iron deficiency, and flu-like symptoms. No drug interactions with epoetin have been reported in humans. The recommended starting epoetin dosage in patients with chronic renal failure is 50-100 IU/kg three times weekly. Epoetin is available only as an injection for i.v. or s.c. administration. Epoetin provides a new therapeutic approach to the treatment of anemia associated with chronic renal failure in hemodialysis, peritoneal dialysis, and predialysis patients. Benefits of epoetin therapy include reduced need for blood transfusions, the amelioration of anemic symptoms, and an improved quality of life.
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PMID:Epoetin: human recombinant erythropoietin. 268 Feb 41

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


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