Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q86TM3 (cage)
 29,987 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The pathophysiological mechanisms of hypercalcaemia were assessed in 50 rehydrated patients with cancer-associated hypercalcaemia. Surprisingly, renal tubular calcium reabsorption appeared to increase progressively as serum calcium rose, suggesting that the nomogram used for the calculation may have been inaccurate, in absolute terms, probably due to its failure to take account of the levels of urinary sodium excretion. There were significant differences in the mechanisms of hypercalcaemia in different patient subgroups, however, independent of differences in urinary sodium excretion. In those with few or no bone metastases, increased renal tubular calcium reabsorption was the principal cause of hypercalcaemia, often in association with increased bone resorption. These abnormalities were thought to reflect the renal and skeletal actions of a tumour-associated humoral mediator. The main cause of hypercalcaemia in those with extensive metastatic bone disease was increased bone resorption, with contributions from impairment of glomerular filtration rate and, to a minor extent, increased renal tubular calcium reabsorption. These abnormalities were thought to reflect a mainly local-osteolytic mechanism of hypercalcaemia with secondary impairment of GFR. Of all the biochemical variables assessed pre-treatment, the renal tubular component of hypercalcaemia correlated most strongly with post-treatment serum calcium values (r = 0.61, P less than 0.001). Because of their generally lower levels of renal tubular calcium reabsorption, patients with extensive skeletal metastases also had significantly lower post treatment calcium values than patients with few or no metastases (P less than 0.05). These data indicate that the pathophysiological mechanisms of hypercalcaemia are a major determinant of the calcium lowering response after antihypercalcaemic treatment. This should be taken into account during comparative studies of antihypercalcaemic therapy in patients with malignancy.
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PMID:Malignancy-associated hypercalcaemia: relationship between mechanisms of hypercalcaemia and response to antihypercalcaemic therapy. 297 9

The Lambert-Eaton myasthenic syndrome is associated in about 65% of cases with small cell carcinoma, a tumour of neurosecretory origin. It is characterised physiologically by a decrease in the nerve evoked quantal release of acetylcholine, and in the resting non-quantal release ("molecular leakage"). The associations with autoimmune disease, with other autoantibodies, with HLA-B8, and with the IgG heavy chain marker Glm (2) are consistent with an autoimmune aetiology. Clinical and electromyographic responses to plasma exchange point to a humorally mediated disorder. This has been substantiated by passive transfer of the the main electrophysiological features of LEMS to mice by daily injections of LEMS IgG. Plasma was no more effective in inducing the electrophysiological changes than the IgG fraction. The decrease in quantal content appeared closely to follow the level of human IgG in the mouse serum and complement (C5) deficient mice were as susceptible as normal controls. The principal physiological abnormalities are both Ca2+ dependent processes, suggesting that a defect in Ca2+ transport may underlie the disorder. Preliminary studies of quantal content at low Ca2+ concentrations in mice injected with LEMS IgG suggest the functional loss of 40% of Ca2+ channels. Electron microscopic freeze fracture studies in such animals show, as in the human disease, a significant reduction in the number of active zone particles which are believed to represent Ca2+ channels. Thus it seems likely that the disorder of acetylcholine release is due to an IgG antibody directed to nerve terminal determinants that include the Ca2+ channels or structures closely related to them. In cancer-associated LEMS, the autoantibody response may initially be made to similar determinants on the tumour cell membrane, cross-reactivity of the antibody with nerve terminal determinants leading to the disorder of transmitter release.
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PMID:Lambert-Eaton myasthenic syndrome. 298 46

Washed and permeabilized human erythrocyte ghosts were found to discharge calcium on treatment with ATP. Concomitantly, there was a decrease in phosphatidylinositol (PI) and an increase in phosphatidylinositol-4-phosphate (PIP) and phosphatidylinositol-4,5-bisphosphate (PIP2). These results support the hypothesis that an inositide shuttle, PI in equilibrium PIP in equilibrium PIP2, operates to maintain intracellular Ca2+ levels. The cation is thought to be sequestered in a cage formed by the head groups of two acidic phospholipid molecules, e.g., phosphatidylserine and phosphatidylinositol, with participation of both PO and fatty acid ester CO groups. These cages are stabilized by inter-headgroup hydrogen bonding. When the inositol group is phosphorylated in positions 4 and 5, inter-lipid hydrogen bonding is disrupted and the cage opens to release its Ca2+.
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PMID:Phosphorylation of erythrocyte membrane liberates calcium. 301 Sep 66

The effect of coprophagy on apparent neutral detergent fiber (NDF) digestibility, and calcium absorption was evaluated by housing rats in four types of cages: regular, metabolic, and two anticoprophagy cages: a short linear tube cage which allowed the rat forward and backward movement of about one-half a body length and a long tube cage assembled to form a square which allowed the rat to move in one direction through the tube but not turn around. Three-day weight gains of animals in the regular or metabolism cages were greater than those of rats housed in either anticoprophagy cage. In contrast, average food intake did not differ among the four housing conditions. Wet, but not dry, fecal weights were greater in the two groups of rats in the anticoprophagy cages. Neither fecal NDF (% dry wt) nor apparent NDF digestibility was affected by housing conditions. Apparent calcium absorption was decreased by the anticoprophagy housing. The differences in body weight and apparent calcium absorption suggest that prevention of coprophagy in the rats produces significant changes in the efficiency of food and nutrient utilization. The failure to detect differences in NDF digestibility indicates that coprophagy has little impact on the study of fiber digestibility.
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PMID:Effect of preventing coprophagy in the rat on neutral detergent fiber digestibility and apparent calcium absorption. 301 4

Eight patients with cancer associated hypercalcaemia were treated with the combination of aminohydroxypropylidene diphosphonate and salmon calcitonin for six days. Serum calcium concentration fell significantly within 24 hours of starting treatment due to a reduction in bone resorption and renal tubular calcium reabsorption. In the longer term hypercalcaemia was controlled by a further progressive reduction in bone resorption, which persisted for six days after treatment was stopped. Renal tubular calcium reabsorption, however, remained suppressed only during drug treatment. The rapid fall in serum calcium was attributable to the acute renal and skeletal effects of calcitonin, whereas in the longer term control of hypercalcaemia was due to diphosphonate mediated suppression of bone resorption. In view of the rapid effect and lack of toxicity, combined treatment with aminohydroxypropylidene diphosphonate and calcitonin would be of particular value in patients with severe hypercalcaemia in whom a quick but sustained reduction in the serum calcium concentration is desired.
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PMID:Treatment of cancer associated hypercalcaemia with combined aminohydroxypropylidene diphosphonate and calcitonin. 308 13

Clearance and in vitro microperfusion studies were performed in rabbits to determine the effect of cisplatin on proximal straight tubule transport of calcium and magnesium. Rabbits were injected with cisplatin (2.5 mg/kg i.p. once weekly) for 3 weeks, whereas control rabbits received normal saline solution which served as a diluent for cisplatin. In 5 rabbits, 24-hour clearance studies were performed with the aid of a metabolic cage. Following cisplatin treatment, fractional excretion of magnesium rose significantly (73.3 +/- 11.5 vs. 111.4 +/- 17.5%). Glomerular filtration rate fell with cisplatin treatment (4.05 +/- 0.76 vs. 2.81 +/- 28 ml/min). There was no difference in fractional excretion of calcium (26.3 +/- 9.5 vs. 22.7 +/- 3.2%). The cortical and juxtamedullary proximal straight tubules were perfused in vitro. Net volume absorption was the same in the control and cisplatin-treated rabbits. However, there was a significant reduction in JCa (cortical 0.57 +/- 0.10 vs. -0.10 +/- 0.12 pmol/min/mm; juxtamedullary 0.96 +/- 0.17 vs. 0.31 +/- 0.37 pmol/min/mm) and JMg (cortical 0.43 +/- 0.08 vs. -0.15 +/- 0.07 pmol/min/mm; juxtamedullary 0.40 +/- 0.27 vs. -0.30 +/- 0.28 pmol/min/mm). In contrast to chronic administration, acute addition of cisplatin into the bath had no effect on JCa and JMg in the cortical and juxtamedullary proximal straight tubules. These data indicate that chronic but not acute cisplatin treatment depresses the transport of calcium and magnesium in the cortical and juxtamedullary nephrons of the proximal straight tubule of the rabbit.
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PMID:Effect of cisplatin on proximal straight tubule transport of divalent cations in the rabbit. 338 Feb 20

1. We have previously reported reduced blood pH and plasma bicarbonate in young Okamoto-Aoki spontaneously hypertensive rats (SHR) compared with normotensive Wistar-Kyoto rats (WKY). Acid loading with 1.5% (w/v) NH4Cl as the sole drinking fluid produced identical falls in blood pH, the difference remaining significant. 2. The ability of SHR to excrete acid and alkaline loads was compared with that of WKY under metabolic cage conditions. The effects of such manipulations on urinary sodium, potassium, calcium and phosphate excretion were also determined. 3. No difference was found in the ability to excrete an acid load or to reduce urine pH. Neither total urinary ammonium ion nor titratable acid differed significantly between the strains under either baseline or acid-loading conditions. 4. Baseline urinary bicarbonate excretion was not significantly different between strains but intraperitoneal administration of NaHCO3 at 2.0 mmol/kg body weight resulted in enhanced excretion in the SHR (SHR vs WKY: 625.2 +/- 71.5 vs 381.8 +/- 40.6 mumol 24 h-1 kg-1 body weight, P less than 0.01, mean +/- SEM). 5. No difference in urinary sodium or potassium excretion was observed between SHR and WKY, but basal calcium and phosphate excretion were reduced in SHR (P less than 0.05). 6. Increased urinary bicarbonate excretion in the presence of significantly reduced plasma bicarbonate suggests reduced tubular reabsorption of bicarbonate, which may contribute to the mild metabolic acidosis in young SHR.
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PMID:Pathogenesis of abnormal acid-base balance in the young spontaneously hypertensive rat. 340 22

The nucleocapsid of the enveloped double-stranded RNA bacteriophage phi 6 was isolated by extraction with the nonionic detergent Triton X-114 and subjected to disruption analysis with chelating and protein-denaturing agents. The subnucleocapsid particles were separated in rate-zonal sucrose gradients, and their ultrastructure and protein composition were analyzed. The role of divalent cations in the nucleocapsid structure was studied by using a precipitation assay of the isolated nucleocapsid proteins. The phi 6 nucleocapsid had a cagelike skeleton consisting of a single polypeptide species (P1). Two other proteins (P2 and P4) were associated with the P1 cage. These three early proteins were previously known to be involved in the RNA synthesis machinery of the virus. The stability of the nucleocapsid surface lattice consisting of protein P8 was dependent on Ca2+ ions.
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PMID:The nucleocapsid of the lipid-containing double-stranded RNA bacteriophage phi 6 contains a protein skeleton consisting of a single polypeptide species. 359 79

Single Comb White Leghorn (SCWL) hens were given feeds (2975 kcal ME/kg) that were marginally deficient in protein (15%) and calcium (3.0%). Negative control was as a mash, whereas an experimental mixture had the same formulation, but 5 of the 15% protein was soybean pellets in place of the meal and 2 of the 3% calcium was oyster shell flakes. A complete cafeteria system acted as a positive control and provided pellets, oyster shell, and a 10% protein-1% calcium mash (2975 kcal ME/kg) separately in a three-compartment trough. Feed treatments were imposed from 24 to 40 weeks of age on hens kept one and two/cage. Performance effects, because of the feed treatments, were not apparent until after 8 weeks of experimentation. Production was sustained by the pellet-oyster shell feed mixture when birds given the complete mash declined. Feeds had immediate effects on egg quality. Egg shell deformation and albumen Haugh values were highest with the complete mash and lowest for the cafeteria system, while the complete mixture was generally between these extremes. Hens kept two/cage consumed more feed than those one/cage and responded similarly to each treatment, but the reduced performance associated with increased density was not alleviated.
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PMID:Egg quality and hen performance responses to protein-calcium deficiency, cafeteria feeding, and cage density. 373 24

Cisplatin (cis-platinum) has been shown to lower cancer-associated humoral hypercalcemia in an animal model and to inhibit bone resorption in vitro. This prospective study was designed to evaluate the efficacy of cisplatin in treating cancer-associated hypercalcemia in humans. Thirteen patients with severe hypercalcemia refractory to rehydration were treated with a 24-hour infusion of cisplatin, 100 mg/m2. Serial measurements of serum calcium and tumor size were made following cisplatin treatment and compared with pretreatment values. Nine patients (69%) achieved normocalcemia after treatment with cisplatin; and mean duration of benefit was 38 days in these patients. No reduction in tumor size was seen. All patients died of progressive cancer. We conclude that cisplatin can control malignant hypercalcemia for relatively long periods, and that its mechanism of action is not due to a reduction in tumor size.
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PMID:Treatment of cancer-associated hypercalcemia with cisplatin. 381 52


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