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 effect of hemolysis and infection/stasis on pigment gallstones was assessed by comparing the composition of stones from (1) U.S. patients without hemolysis or cirrhosis, (2) U.S. patients with sickle cell disease, and (3) Japanese patients with biliary infections. Gallstone composition was quantitated by infrared spectroscopy and chemical analyses. Gallstones from patients with sickle cell anemia contained more pigment, carbonate, calcium, and measured components than stones from U.S. patients without hemolysis (P less than 0.05). However, the similar types of calcium salts in black stones from patients with and without sickle cell anemia suggested that intermittent hemolysis may be a potential mechanism in the formation of black stones found in the general population. In Japanese patients with brown pigment stones, there was an absence of calcium carbonate, low levels of calcium phosphate, and the presence of calcium salts of fatty acids (P less than 0.05). Thus, the accompanying stasis and/or infection in this latter group was associated with the formation of a distinctive stone type and was not involved in the formation of the black stones. The similarly small proportion of cholesterol in each of these groups suggested that it was present due to coprecipitation rather than to cholesterol supersaturation.
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PMID:Pigment gallstone composition in patients with hemolysis or infection/stasis. 369 61

The aim of this study was to evaluate the influence of LCD on bone metabolism, and assess the indication of LCD. Fourteen patients on CAPD (m = 8, f = 6) were converted to LCD following over 1 year on standard calcium dialysate (1.75 mmol/l; SCD) treatment, and followed for 1 year. The biochemical measurements included plasma levels of Ca, P, ALP, and i-PTH. The bone mineral density (BMD) was evaluated using dual energy x-ray absorptiometry. Ca-carbonate and calcitriol were administered to maintain plasma Ca levels within the normal range. The patients were divided into three groups on the basis of the i-PTH levels just before the conversion to LCD. Group 1; n = 5, i-PTH < 65. Group 2; n = 5, 65 < or = i-PTH < 200. Group 3; n = 4, 200 < or = i-PTH (pg/ml). Mean BMD Z scores decreased significantly in group 3. Mean serum i-PTH significantly increased in all groups. These results suggest that LCD is effective for treating adynamic bone disease, which is seen in high frequency in patients undergoing peritoneal dialysis. However, these results also pointed to the disadvantage of worsening the secondary hyperparathyroidism. In conclusion, LCD should be used carefully in patients whose i-PTH levels are high, because of the possibility of bone mineral loss.
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PMID:[The impact of low calcium dialysate (1.25 mmol/l; LCD) on bone metabolism in CAPD patients]. 965 8

Band 3 proteins, members of the anion exchange family of proteins (AE 0-3), are involved in a number of physiological activities such as cell volume and osmotic homeostasis, HCO3-/Cl- exchange, red cell aging, IgG binding and cellular removal, and the maintenance of the structural integrity of cells. They are present in the membranes of all cells and cellular organelles examined including Golgi, mitochondria and nuclei. The first polymorphisms of band 3 discovered were the asymptomatic band 3 Memphis variants carrying the Lys --> Gly substitution at position 56 in the cytoplasmic tail, and band 3 Texas (high transport band 3 Texas) with a mutation in the critical transmembrane, anion transport domain (Pro --> Leu substitution at position 868). The rate at which band 3 mutations were discovered accelerated in the mid 1990s and there are now over 50 known. The most common polymorphisms of band 3 are the Diego blood group antigens which reside on extracellular loops of the protein. Southeast Asia ovalocytosis (SAO; a nine amino acid deletion of residues 400-408) is a band 3 mutation known only in the heterozygous state in which it does not cause disease. It is thought to confer resistance to malaria by altering red cell deformability. Band 3 mutations are responsible for a subset of the heterogeneous group of disorders known as hereditary spherocytosis (HS). HS is a relatively common congenital or inherited group of anemias characterized by chronic hemolysis and abnormal red cell morphology. Red cells in the subset of HS with band 3 mutations behave like they are band 3 deficient either because the mutant protein is not incorporated into the membrane or because it is not functional. HS can be caused by mutations in any of at least 5 proteins involved in membrane stability. Band 3 mutations are associated with diseases in cells besides erythrocytes. For example, 2 types of distal renal tubular acidosis are the result of band 3 mutations either alone or combined with SAO. Band 3 alterations are implicated in neurological diseases such as familial paroxysmal dyskinesia, idiopathic generalized epilepsies, and neuro- or choreoacanthocytosis although they have not been demonstrated to be causative. Mutations in other genes can cause changes in band 3. An example is sickle cell anemia where the increased oxidation causes accelerated aging of band 3 and increased IgG binding and cellular removal.
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PMID:Band 3 and its alterations in health and disease. 1509 83

Survival of human and animal cells requires avoidance of excessive alterations of cell volume. The osmolarity amassed by cellular accumulation of organic substances must be compensated by lowering cytosolic ion concentrations. The Na+/K+ ATPase extrudes Na+ in exchange for K+, which can permeate the cell membrane through K+ channels. K+ exit generates a cell-negative potential difference across the cell membrane, driving the exit of anions such as Cl-. The low cytosolic Cl- concentrations counterbalance the excess cellular osmolarity by organic substances. Cell volume regulation following cell swelling involves releasing ions through activation of K+ channels and/or anion channels, KCl-cotransport, or parallel activation of K+/H+ exchange and Cl-/HCO3- exchange. Cell volume regulation following cell shrinkage involves accumulation of ions through activation of Na+,K+,2Cl- cotransport, Na+/H+ exchange in parallel to Cl-/HCO3- exchange, or Na+ channels. The Na+ taken up is extruded by the Na+/K+ ATPase in exchange for K+. Shrunken cells further accumulate organic osmolytes such as sorbitol and glycerophosphorylcholine, and monomeric amino acids by altered metabolism and myoinositol (inositol), betaine, taurine, and amino acids by Na+ coupled transport. They release osmolytes during cell swelling. Challenges of cell volume homeostasis include transport, hormones, transmitters, and drugs. Moreover, alterations of cell volume participate in the machinery regulating cell proliferation and apoptotic cell death. Deranged cell volume regulation significantly contributes to the pathophysiology of several disorders such as liver insufficiency, diabetic ketoacidosis, hypercatabolism, fibrosing disease, sickle cell anemia, and infection.
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PMID:Mechanisms and significance of cell volume regulation. 1792 74

Bone disease with osteoporosis and osteomalacia are common in sickle cell disease (SCD). Some patients have vitamin D deficiency and low bone mineral density (BMD). The role of vitamin D and calcium supplementation to restore bone health in SCD has not been well studied. In 14 adults with SCD, we measured 25(OH)D (25-hydroxyvitamin D) and BMD at the femoral neck, lumbar spine, and distal third of the ulna plus radius, along with markers of bone resorption (CTx; C-terminal component of pro-collagen type I) and bone formation (osteocalcin) before and after 12 months of vitamin D(2) and calcium carbonate treatment. Pretreatment, all patients were vitamin D deficient with a mean 25(OH)D level of 11.6 [corrected] +/- 4 [corrected] ng/ml, had low BMD at the lumbar spine (L-spine), 0.87 +/- 0.11 g/cm(2) (mean Z-score of -2.6 3 +/- 0.71 SD and T score of -2.31 +/- 0.75 SD), femoral neck, 0.8 +/- 0.18 g/cm(2) (mean Z-score -1.36 +/- 0.84, T-score -1.14 +/- 0.75), and the distal radius and ulna, 0.6 +/- 0.17 g/cm(2) (mean Z-score -1.18 +/- 0.79, T-score -1.01 +/- 0.74) and had elevated CTx (0.87 +/- 0.5 ng/ml) and osteocalcin levels (12.3 +/- 3.7 ng/mul). After treatment, all patients corrected their 25(OH)D level (34.6 [corrected] +/- 11 [corrected] ng/ml) (P < 0.001) with a 3.6% +/- 3.9% increase in BMD at the L-spine (P = 0.009), 4.6% +/- 8.5% increase at the femoral neck (P = 0.05) and 6.5% +/- 12.6% increase at the distal radius plus ulna (P = 0.09). CTx, osteocalcin, and PTH(i) levels were unchanged. Treatment of adult SCD with vitamin D and calcium can restore 25(OH)D levels to normal and improve BMD, but, markers of bone resorption remained unchanged. Screening for vitamin D deficiency and BMD in SCD patients seems warranted.
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PMID:Sickle cell bone disease: response to vitamin D and calcium. 1792 48