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)

To identify factors affecting bilirubin excretion, the effects of bile flow and bile salt excretion on bilirubin output into bile have been examined in normobilirubinemic, cholecystectomized patients with balloon-occludable, reinfusion T-tubes, 8 patients with cholesterol (CS) and 2 with pigment (PS) gallstones. Another patient with pigment gallstones, sickle cell disease (SS), and stable jaundice was studied to examine the mechanism by which an increased bilirubin load was excreted. Total bilirubin was almost entirely conjugated and excretion was related linearly to bile salt excretion PS and CS subjects; one-third of bilirubin excretion was bile salt independent and two-thirds was bile salt associated. In the SS patient 90% of the bilirubin excretion was independent of bile salt output. In PS and CS patients, bilirubin output was linearly related to bile flow, but the SS patient showed significant bilirubin excretion at low flow rates. CS and PS patients had similar patterns of bilirubin excretion, but the increased bilirubin load in the SS patient was excreted independently of bile salts. In the SS patient, unconjugated bilirubin output was hyperbolically related to bile salts output and represented a maximum of 3% of the total bilirubin output. The bile salt-independent excretion of conjugated bilirubin suggests that micelles were not required for transport into bile; whereas the hyperbolic relationship for unconjugated bilirubin and bile salt output, similar to that of the micellar lipids. cholesterol, and phospholipids, suggests interaction with micelles.
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PMID:Factors affecting bilirubin excretion in patients with cholesterol or pigment gallstones. 83 16

Severe hyponatremia has been observed in three children with sickle cell disease, and mild hyponatremia was noted during 36% of random hospitalizations for sickle crisis secondary to vasoocclusion or infection. Serum and urinary electrolytes were therefore studied in such patients. Hyponatremia was found in 52% of patients hospitalized with pain and/or fever, even though they received large amounts of sodium intravenously. Urine sodium losses were high with frequent negative sodium balance and weight loss. When well, these patients did not demonstrate hyponatremia, although urinary salt losses appeared to be just as high, suggesting compensatory salt intake when the children are well. It is essential to monitor electrolytes and urinary losses to manage sickle crisis properly. Six to 11 mEq/kg/day of sodium is suggested as a usual need of these patients during crisis. Sickle cell disease patients have, in addition to the better known defect in concentration of urine, a functional defect in dilution of urine at least during periods of "crisis".
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PMID:Hyponatremia in sickle cell disease. A renal salt-losing state. 127 Nov 42

Polymerization-depolymerization of proteins within cells and subcellular organelles may have powerful osmotic effects. As a model to study these we analyzed the predicted volume changes following hemoglobin (Hb) S polymerization in sickle cell anemia (SS) red cells with different initial volumes. The theoretical analysis predicted that dehydrated SS red cells may sustain large polymerization-induced volume shifts whose direction would depend on whether or not small solutes were excluded from polymer-associated water. Experiments with SS cells from promptly fractionated venous blood showed oxygenation-induced swelling, maximal in the densest cells, in support of nonexclusion models. The predicted extent of cell dehydration on polymerization was strongly influenced by factors such as the dilution of residual soluble Hb and the increased osmotic contribution of Hb in cells dehydrated by salt loss, largely overlooked in the past. The osmotic effects of polymer formation may thus play an important part in microcirculatory infarction by dense SS cells, as they become even denser and stiffer during deoxygenation in the capillaries.
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PMID:Osmotic effects of protein polymerization: analysis of volume changes in sickle cell anemia red cells following deoxy-hemoglobin S polymerization. 187 1

Renal hemodynamics and solute and water handling were evaluated in 19 sickle cell patients and 8 matched normal subjects during water diuresis, before and after acute oral administration of a nonsteroidal antiinflammatory drug (NSAID). Baseline GFR and RPF were higher in the patients compared to the normals. In contrast to normals, indomethacin and sulindac induced a 16% and 14% decrease in GFR, respectively. Indomethacin resulted in a slight increase in UOsm in normals, but a substantially greater rise in the patients. Following indomethacin a greater fall in FENa, fractional solute delivery to the diluting segment of the nephron [(CH2O + CNa + K)/GFR], fractional solute reabsorption in the diluting segment [CH2O/GFR] and the fraction of distally delivered solute reabsorbed [CH2O/(CH2O + CNa + K)] was observed in the sickle cell patients than in the normal subjects. A similar trend, but of significantly lesser magnitude than that induced by indomethacin, was observed following sulindac in the sickle cell patient. The data imply that the supranormal GFR observed in the sickle cell patients was prostaglandin-mediated. The effects of NSAID's on renal solute and water handling in the sickle cell patients are compatible with a prostaglandin-dependent decreased salt reabsorption in the medullary thick ascending limb of Henle, together with a hyperfunctioning proximal tubule. The data also imply an additional indomethacin-sensitive antinatriuretic effect in the diluting segment in these patients. Moreover, the results suggest that in sickle cell anemia sulindac may not have a "renal sparing" advantage over other NSAID's.
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PMID:Effects of nonsteroidal antiinflammatory drugs on renal function in sickle cell anemia. 319 68

Since the rate of polymerization of sickle hemoglobin is exquisitely dependent on its concentration, a small reduction in intracellular hemoglobin concentration should cause a significant inhibition of sickling. In three patients with homozygous sickle cell anemia, sustained hyponatremia was induced by a program consisting of a high fluid intake, a low salt diet and a vasopressin analog, DDAVP. During periods of hyponatremia, mean corpuscular hemoglobin concentration (MCHC) fell 13% and in vitro sickling was reduced as assessed by morphology and oxygen affinity. The frequency and duration of sickle cell crises appeared to be decreased during periods when patients were hyponatremic. These preliminary results indicate that reduction in intracellular hemoglobin concentration is an effective approach to the treatment of sickle cell anemia.
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PMID:The treatment of sickle cell anemia with induced hyponatremia. 715 56

Arterial blood pressures (BPs) in 187 adult patients with sickle cell disease, casually recorded during hospitalization or clinic visits, were compared with BPs from age- and sex-matched populations of black Americans. The BPs in those with sickle cell disease were significantly lower than those in the control populations in all ages and did not demonstrate the expected rise with advancing age. In these patients, there was no difference between BP and sex, degree of anemia, or hemoglobin genotype. Four patients had diastolic and two had systolic hypertension. The prevalence of hypertension was significantly less than that in the block population. These BP findings in sickle cell disease may be due to the renal tubular defect responsible for increased sodium and water excretion, which may blunt the plasma volume expansion necessary for sustained hypertension and thus promote lower arterial pressures, similar to that situation observed in patients with salt-losing nephritis.
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PMID:Arterial blood pressure in adults with sickle cell disease. 723 8

Iron studies were performed on 25 children with homozygous sickle cell disease. The majority (80%) of patients had never been transfused. Surprisingly, the results showed that all had low serum iron and low transferrin saturation. Three children had no marrow iron stores while the rest had diminished amounts of iron. This may be an important finding in view of recent efforts at fortifying common salt with iron. The exact effects of iron deficiency on sickle cell disease are not known and a controlled trial is called for.
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PMID:Iron deficiency in sicle cell disease. 737 58

The incubation of red blood cells in high concentrations of sodium bicarbonate produces a net influx of salt and water resulting in the dilution of cell hemoglobin. After reinfusion into the donor, cells swollen in this manner can be readily identified in peripheral blood samples by their low density on phthalate gradients. It is proposed that this manipulation of cell water content may have therapeutic implications for sickle cell disease, since the rate of deoxyhemoglobin S gelation is retarded by small reductions in hemoglobin concentration.
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PMID:Cell density profile as a measure of erythrocyte hydration: therapeutic alteration of salt and water content in normal and SS red blood cells. 739 91

A concentrated, DNA-free extract of histone acetylase A was prepared from calf thymus tissues in two simple steps, which exploit the ability of polyethylene glycol to precipitate both nucleic acids and proteins from solutions containing high concentrations of salt (Alberts, B., and Herrick, G. (1971) Methods Enzymol. 21, 198-217). This extract was then chromatographed on four successive columns. The use of 75 microgram/ml of insulin as a carrier protein in all of these later steps, plus the inclusion of 1 M urea in some column buffers, has been useful in improving both the yield and reproducibility of the purification. The highly active enzyme obtained has a molecular weight of about 70,000, and the best fractions could be about 30% pure. Our data indicate that the acetylase A is only a very minor protein in cells, being present in perhaps a few thousand molecules per cell.
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PMID:Extensive purification of histone acetylase A, the major histone N-acetyl transferase activity detected in mammalian cell nuclei. 744 May 47

Butyrate analogues have been shown to increase fetal hemoglobin (HbF) production in vitro and in vivo. Sodium phenylbutyrate (SPB), an oral agent used to treat individuals with urea-cycle disorders, has been shown to increase HbF in nonanemic individuals and in individuals with sickle cell disease. We have treated eleven patients with homozygous beta thalassemia (three transfusion dependent) and one sickle-beta-thalassemia patient with 20 g/d (forty 500-mg tablets) of SPB for 41 to 460 days. All patients showed an increase in the percent of F reticulocytes associated with treatment, but only four patients responded by increasing their Hb levels by greater than 1 g/dL (mean increase, 2.1 g/dL; range, 1.2 to 2.8 g/dL). None of the transfusion-dependent thalassemia subjects responded. Increase in Hb was associated with an increase in red blood cell number (mean increase, 0.62 x 10(12)/L), and mean corpuscular volume (mean increase, 6 fL). Changes in percent HbF, absolute HbF levels, or alpha- to non-alpha-globin ratios as measured by levels of mRNA and globin protein in peripheral blood did not correlate with response to treatment. Response to treatment was not associated with the type of beta-globin mutation, but baseline erythropoietin levels of greater than 120 mU/mL was seen in all responders and only two of eight nonresponders to SPB. Compliance with treatment was greater than 90% as measured by pill counts. Side effects of the drug included weight gain and/or edema caused by increase salt load in 2/12, transient epigastric discomfort in 7/12, and abnormal body odor in 3/12 subjects. Two splenectomized patients who were not on prophylactic antibiotics developed sepsis while on treatment. We conclude that SPB increases Hb in some patients with thalassemia, but the precise mechanism of action is unknown.
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PMID:Oral sodium phenylbutyrate therapy in homozygous beta thalassemia: a clinical trial. 752 72


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