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)

A 23-kDa, soluble, calcium-binding photoreceptor-specific protein (23-kDa) has been shown to be identical to recoverin and the cancer-associated retinopathy protein. Recoverin has been reported to activate guanylate cyclase to increase the amount of cyclic GMP and thereby reopen cation channels within the photoreceptor cells. In this study, the 23-kDa protein was purified from bovine retinas and monospecific antibodies against it were generated in rabbits. Western analysis demonstrated 23-kDa in retinas from human, monkey, bovine, dog, rabbit, rat, mouse, frog, chameleon and iguana although it was not detected in chicken or fly retinas. No immunoreactivity was observed in any non-retinal tissues except the pineal gland. The 23-kDa protein was detected, by Western analysis, at postnatal day 5 in the mouse retina and it increased in amount in parallel with the differentiation of the photoreceptor cells in normal mice and it also decreased in parallel with their degeneration in the rd mouse. Immunocytochemical analysis of the adult mouse retina showed that 23-kDa is restricted primarily to the inner segments of the photoreceptor cells and, unlike arrestin, its localization did not shift in response to light/dark changes.
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PMID:Developmental appearance, species and tissue specificity of mouse 23-kDa, a retinal calcium-binding protein (recoverin). 840 85

One current hypothesis for the initiation of Ca2+ entry into nonelectrically excitable cells proposes that Ca2+ entry is linked to the state of filling of intracellular Ca2+ stores. In the human T lymphocyte cell line Jurkat, stimulation of the antigen receptor leads to release of Ca2+ from internal stores and influx of extracellular Ca2+. Similarly, treatment of Jurkat cells with the tumor promoter thapsigargin induced release of Ca2+ from internal stores and also resulted in influx of extracellular Ca2+. Initiation of Ca2+ entry by thapsigargin was blocked by chelation of Ca2+ released from the internal storage pool. The Ca2+ entry pathway also could be initiated by an increase in the intracellular concentration of Ca2+ after photolysis of the Ca(2+)-cage, nitr-5. Thus, three separate treatments that caused an increase in the intracellular concentration of Ca2+ initiated Ca2+ influx in Jurkat cells. In all cases, Ca(2+)-initiated Ca2+ influx was blocked by treatment with any of three phenothiazines or W-7, suggesting that it is mediated by calmodulin. These data suggest that release of Ca2+ from internal stores is not linked capacitatively to Ca2+ entry but that initiation is linked instead by Ca2+ itself, perhaps via calmodulin.
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PMID:Increased intracellular Ca2+ induces Ca2+ influx in human T lymphocytes. 844 15

Hypercalcaemia is the most common metabolic complication of malignant disease. It is an important cause of morbidity in cancer patients and is potentially amendable to treatment. Bone metastases are rarely the cause of hypercalcaemia in malignancy, the elevation in calcium concentrations usually resulting from the effects of humoral mediators released by the tumour. Many factors isolated from tumours have the potential to cause hypercalcaemia, but the most important is parathyroid hormone related protein (PTHrP), a peptide which mimics the effect of PTH. Treatment of cancer associated hypercalcaemia is based on an initial phase of volume repletion with isotonic saline, followed by drug treatment to inhibit bone resorption. Bisphosphonates are the most widely used agents in the treatment of such bone resorption, are very effective and have minimal toxicity. Gallium nitrate is also effective but less widely used. The combination of bisphosphonates and calcitonin has been found to be particularly useful in patients with severe hypercalcaemia, since this gives a more rapid reduction in serum calcium values than can be achieved with bisphosphonate alone. In the longer term, effective control of hypercalcaemia depends on treating the primary tumour. In the majority of cases this is not possible, however, because of the state of disease progression or the nature of the tumour. Anti-hypercalcaemic therapy is an important palliative measure in cancer patients who have symptoms of hypercalcaemia. Treatment does little to alter the long term prognosis but often results in an improvement in symptoms such that the majority may be made well enough to be discharged from hospital care.
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PMID:Pathogenesis and management of cancer associated hypercalcaemia. 856 93

Vertebral columns of female and male breeding rabbits, kept in conventional cages or in a group housing system, were investigated by spot checks anatomically and radiographically in regard to deformations of the vertebral column. It should be proved, whether depending on the housing system and the opportunity of locomotion the male and female rabbits get deformations of the vertebral column. The observations show, that the bucks had no deformations, whereas the does had. It became evident, that frequence and degree of deformation were dependent on the cage size. It provokes deformations by "flat sitting" as well as the systemic hypoplasia of bony tissue caused by deficiency of locomotion. Reproduction provokes deformations of the vertebral column, too, causing alterations in the static-dynamic forces of trunk construction as well as a high need and metabolism of calcium. The causing factors and the relevance of animal protection are discussed.
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PMID:[Scoliosis, lordosis and kyphosis in breeding rabbits]. 876 92

The effect of high-intensity training on the in vivo lower leg fracture strength during muscle contraction was investigated in osteoporotic rats. 20 Wistar rats were ovariectomized and given a low calcium (0.01%) diet. 7 weeks after ovariectomy they were randomized into training (T) and sedentary (S). The S group was kept cage-confined without any intervention. The T group ran on a treadmill with 10 degrees inclination 5/7 days for 8 weeks. A maximum intensity of 27 m/min was reached after 4 weeks. After 8 weeks, the right lower legs of the anesthetized animals were loaded in three-point ventral bending until fracture occurred during electrically-induced muscle contraction. The left tibiae were excised and fractured at the same level as the right tibiae. Weight gain was equal in the two groups. Energy absorption and deflection at fracture were significantly higher in the T group than in the S group in vivo during muscle contraction. In vitro, there were no significant differences in mechanical results. The mediolateral outer diameter was larger in the T group, and the maximal stress that the tibia could withstand was lower than in the S group. We conclude that 8 weeks of high-intensity training of osteoporotic rats increased the structural lower leg strength during muscle contraction. The reduced maximal stress in the training animals indicates a reduction in bone material quality. The increase of in vivo structural strength must reflect an increased protective effect of muscle contraction due to training.
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PMID:Training increases the in vivo fracture strength in osteoporotic bone. Protection by muscle contraction examined in rat tibiae. 879 42

Recoverin, a photoreceptor-specific calcium-binding protein, is a target for antibodies in human cancer-associated retinopathy. We have studied the binding properties of antirecoverin human autoantibodies and rat monoclonal antibodies (MAbs). The majority of antibodies to recoverin, both in human disease and in animals immunized with recoverin, are directed against the same major immunodominant region, the sequence within the residue 64-70 in proximity to the calcium-binding domain EF-hand 2. The immunodominant epitopes consist of linear and conformational components. Our data demonstrate that the reactivity of autoantibodies was dependent on conformational changes induced by the binding of calcium to recoverin. Some patients' antibodies could be detected by immunocytochemical methods and enzyme linked immunosorbent assay (ELISA); however, their binding was abolished on Western blots; their epitopes were sensitive to SDS treatment. Immunization of Lewis rat with purified recoverin induces antibodies with properties strikingly similar to human autoantibodies. Comparison between the monoclonal antibodies (MAbs) and native autoantibodies showed that the calcium-induced changes in conformation were critical for specificities of the antibody generated. The recoverin region within the sequence 61-82 is a key region for antibody binding; it also contains a major T-cell epitope, and it is highly uveitogenic in Lewis rats.
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PMID:Epitope recognition of recoverin in cancer associated retinopathy: evidence for calcium-dependent conformational epitopes. 889 98

N-benzyl-3,11-azatricyclo[6.3.0.0]undecane and N-octyl-3,11-azatricyclo[6.3.0.0]undecane, two triquinane compounds containing an endocyclic nitrogen atom and differing side-chains, were synthesized by thermal 2 + 2 cycloreversion from the symmetric cage compound pentacyclo[5.4.0.0.0.0]undecane-8,11-dione. The conformation of the cyclic system showed close similarity with the conformation of the hydrate of 4-methyltricyclo[6.3.0.0]undeca-3,11-dione. Both N-benzyl-3,11-azatricyclo[6.3.0.0]undecane and N-octyl-3,11-azatricyclo[6.3.0.0]undecane showed similar suppressant activity on the Ca2+ action potential of guinea-pig papillary muscle--the benzyl (aromatic) derivative fully suppressed the action potential (AP) whilst the aliphatic (octyl) derivative suppressed the AP to about 50% at the same dosages. Similarly, both these compounds (irreversibly) suppressed the chronotropy of spontaneously contracting guinea-pig atria by approximately 30% at concentrations of 1 x 10(-5) M or more.
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PMID:The biological activity of two symmetric amine derivatives of the cis-syn-cis triquinane system. 899 28

Hypercalcaemia is an important cause of morbidity in malignant disease. We studied the efficacy and safety of intravenous ibandronate (a new, potent bisphosphonate) in a multicentre study of 147 patients with severe cancer-associated hypercalcaemia which had been resistant to treatment with rehydration alone. Of 131 randomized patients who were eligible for evaluation, 45 were allocated to receive 2 mg ibandronate, 44 patients to receive 4 mg and 42 patients to receive 6 mg. Serum calcium values fell progressively in each group from day 2, reaching a nadir at day 5, and in some patients normocalcaemia was maintained for up to 36 days after treatment. The 2-mg dose was significantly less effective than the 4-mg or 6-mg dose in correcting hypercalcaemia, as the number of patients who achieved serum calcium values below 2.7 mM after treatment was 50% in the 2-mg group compared with 75.6% in the 4-mg group and 77.4% in the 6-mg group (P < 0.05; 2 mg vs others). In a logistic regression analysis, three factors were found to predict response; ibandronate dose (higher doses were more effective), severity of presenting hypercalcaemia (severe hypercalcaemia was associated with less complete response) and tumour type (patients with breast carcinoma and haematological tumours responded better than those with other tumours). Ibandronate was generally well tolerated and no serious drug-related adverse events were observed. We conclude that ibandronate is a safe, well tolerated and effective treatment for cancer-associated hypercalcaemia, which should prove a useful addition to the current range of therapies available to treat this condition.
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PMID:Dose-response study of ibandronate in the treatment of cancer-associated hypercalcaemia. 901 41

The aim of this study was to investigate the effect of training on the in vivo tibial structural strength during the development of post-ovariectomy osteoporosis. Seventeen mature Wistar rats (215 g) were ovariectomized and randomized into two groups. The sedentary control group was kept cage confined, while 3 days postoperatively the trained group started treadmill running with high intensity for 1 h 5 days a week. All were given a low calcium diet (Ca 0.01%). After 8 weeks the animals were anaesthetized and the right lower legs fractured during muscle contraction in three-point ventral bending. The left legs were fractured at the same level after removal of all soft tissues. Histomorphometry of the meta- and diaphysis of the distal tibiae was performed. Weight-gain was higher in sedentary (108 g) than in trained (61 g) rats (P<0.0001). There were no significant differences in mechanical results between the groups at in vivo or in vitro fracture. Correcting for weight-gain differences did not change these results. Histomorphometry showed no differences between the groups. Corticosterone was higher in trained than in sedentary rats (P<0.02), and corticosterone may have had a negative influence both on muscle and bone. The study could not show an effect of high intensity training in the early phase after ovariectomy on in vivo or in vitro fracture strength.
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PMID:Effect of intensive training on lower leg structural strength: an in vivo study in ovariectomized rats. 924 Oct 27

Calcium ionophore A23187 induced time and concentration dependent production of immunoreactive leukotriene (LT) B4 by equine heparinized whole blood in vitro. Time dependent production of immunoreactive LTB4 by equine neutrophils and immunoreactive LTC4 by equine eosinophils in vitro was also demonstrated. The 5-lipoxygenase activating protein (FLAP) inhibitors, BAY X 1005 and BAY Y 1015, produced concentration dependent inhibition of ionophore-induced LTB4 synthesis by equine whole blood (mean +/- SEM IC50s n = 5; 6.14 +/- 0.28 microM vs. 12.30 +/- 0.75 microM for BAY Y 1015 and BAY X 1005, respectively) and neutrophils (mean +/- SEM IC50s n = 5; 0.003 +/- 0.001 microM vs. 0.045 +/- 0.021 microM for BAY Y 1015 and BAY X 1005, respectively) and LTC4 synthesis by equine eosinophils (mean +/- SEM IC50s n = 5; 0.0036 +/- 0.0002 microM and 0.108 +/- 0.023 microM for BAY Y 1015 and BAY X 1005, respectively) in vitro. In all three assays, BAY Y 1015 was more potent than BAY X 1005, and for both compounds much higher concentrations were required to inhibit LT synthesis by whole blood compared to isolated neutrophils and eosinophils. Plasma concentration-time relationships and pharmacokinetic parameters for BAY Y 1015 administered intravenously and orally to six horses at a dosage of 10 mg/kg in a two period cross-over study were established. The study also evaluated the anti-inflammatory properties of BAY Y 1015 and its ability to inhibit ex vivo whole blood LTB4 synthesis and in vivo LTB4 synthesis in a tissue cage model of acute inflammation. At this dosage, BAY Y 1015 failed to significantly inhibit immunoreactive LTB4 synthesis or the oedema produced by intradermal injection of the mild irritant, carrageenan.
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PMID:Pharmacology of the 5-lipoxygenase inhibitors BAY Y 1015 and BAY X 1005 in the horse. 928 Mar 70


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