Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Systemic mastocytosis occurred as a fatal event in a patient with long-standing polycythemia vera. The patient had been treated over the course of 21 yr with radioactive phosphorus. Possible relationships between mastocytosis and polycythemia vera, and also between mastocytosis and treatment with ionizing radiation, are discussed. Histopathologic and electron microscopic findings are illustrated. Difficulties in establishing the diagnosis of mast cell disease in this setting are also described.
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PMID:Systemic mastocytosis in a patient with polycythemia vera treated with radioactive phosphorus. 30 Feb 55

The molecular structures of three phosphorus-based peptide inhibitors of aspartyl proteinases complexed with penicillopepsin [1, Iva-L-Val-L-Val-StaPOEt [Iva = isovaleryl, StaP = the phosphinic acid analogue of statine [(S)-4-amino-(S)-3-hydroxy-6-methylheptanoic acid] (IvaVVStaPOEt)]; 2, Iva-L-Val-L-Val-L-LeuP-(O)Phe-OMe [LeuP = the phosphinic acid analogue of L-leucine; (O)Phe = L-3-phenyllactic acid; OMe = methyl ester] [Iva VVLP(O)FOMe]; and 3, Cbz-L-Ala-L-Ala-L-LeuP-(O)-Phe-OMe (Cbz = benzyloxycarbonyl) [CbzAALP(O)FOMe]] have been determined by X-ray crystallography and refined to crystallographic agreement factors, R ( = sigma parallel to F0 magnitude of - Fc parallel to/sigma magnitude of F0), of 0.132, 0.131, and 0.134, respectively. These inhibitors were designed to be structural mimics of the tetrahederal transition-state intermediate encountered during aspartic proteinase catalysis. They are potent inhibitors of penicillopepsin with Ki values of 1, 22 nM; 2, 2.8 nM; and 3, 1600 nM, respectively [Bartlett, P. A., Hanson, J. E., & Giannousis, P. P. (1990) J. Org. Chem. 55, 6268-6274]. All three of these phosphorus-based inhibitors bind virtually identically in the active site of penicillopepsin in a manner that closely approximates that expected for the transition state [James, M. N. G., Sielecki, A.R., Hayakawa, K., & Gelb, M. H. (1992) Biochemistry 31, 3872-3886]. The pro-S oxygen atom of the two phosphonate inhibitors and of the phosphinate group of the StaP inhibitor make very short contact distances (approximately 2.4 A) to the carboxyl oxygen atom, O delta 1, of Asp33 on penicillopepsin. We have interpreted this distance and the stereochemical environment of the carboxyl and phosphonate groups in terms of a hydrogen bond that most probably has a symmetric single-well potential energy function. The pro-R oxygen atom is the recipient of a hydrogen bond from the carboxyl group of Asp213. Thus, we are able to assign a neutral status to Asp213 and a partially negatively charged status to Asp33 with reasonable confidence. Similar very short hydrogen bonds involving the active site glutamic acid residues of thermolysin and carboxypeptidase A and the pro-R oxygen of bound phosphonate inhibitors have been reported [Holden, H. M., Tronrud, D. E., Monzingo, A. F., Weaver, L. H., & Matthews, B. W. (1987) Biochemistry 26, 8542-8553; Kim, H., & Lipscomb, W. N. (1991) Biochemistry 30, 8171-8180].(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Crystallographic analysis of transition-state mimics bound to penicillopepsin: phosphorus-containing peptide analogues. 160 44

A 59-year-old male presented with systemic mastocytosis with extensive skeletal involvement resulting in vertebral compression fractures and bone pain. Histomorphometric analysis of bone revealed increased mast cells, elevated static parameters of bone resorption, and low bone formation. Serum calcium, phosphorus, and alkaline phosphatase were normal; however, serum 1,25-dihydroxyvitamin D3 and osteocalcin levels were low. Histamine levels in plasma and urine were elevated. Following therapy with ketotifen, the patient had resolution of bone pain along with decreased flushing and pruritus. Elevated plasma and urine histamine levels normalized, as did 1,25-dihydroxyvitamin D3 and osteocalcin levels. Indices of low bone formation improved on therapy. Eroded surfaces improved but remained elevated. This case is the first demonstration that bone symptoms and histomorphometric change in systemic mastocytosis are reversed with inhibition of mast cell degranulation. The role of mast cells and their products in bone metabolism is poorly understood, but the therapy of bone disease in systemic mastocytosis should include inhibition of the release of mast cell products along with the use of histamine antagonist.
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PMID:Inhibition of mediator release in systemic mastocytosis is associated with reversal of bone changes. 227 Jul 75

A series of phosphonic acid analogues of 2-benzylsuccinate were tested as inhibitors of carboxypeptidase A. The most potent of these, (2RS)-2-benzyl-3-phosphonopropionic acid, had a Ki of 0.22 +/- 0.05 microM, equipotent to (2RS)-2-benzylsuccinate and thus one of the most potent reversible inhibitors known for this enzyme. Lengthening by one methylene group to (2RS)-2-benzyl-4-phosphonobutyric acid increased the Ki to 370 +/- 60 microM. The monoethyl ester (2RS)-2-benzyl-3-(O-ethylphosphono)propionic acid was nearly as potent as (2RS)-2-benzyl-3-phosphonopropionic acid, with a Ki of 0.72 +/- 0.3 microM. The sulphur analogue of the monoethyl ester, 2-ambo-P-ambo-2-benzyl-3-(O-ethylthiophosphono)propionic acid, had a Ki of 2.1 +/- 0.6 microM, nearly as active as (2RS)-2-benzyl-3-(O-ethylphosphono)propionic acid. These phosphonic acids and esters could be considered to be multisubstrate inhibitors of carboxypeptidase A by virtue of their structural analogy with 2-benzylsuccinate. Alternatively, the tetrahedral hybridization at the phosphorus atom suggests that they could be mimicking a tetrahedral transition state for the enzyme-catalysed hydrolysis of substrate.
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PMID:3-Phosphonopropionic acids inhibit carboxypeptidase A as multisubstrate analogues or transition-state analogues. 408 24

Six pigs, initially of 35 kg mean live weight, were each fitted with a re-entrant cannula. This was formed on either side of a short pouch of duodenum into which the pancreatic duct opened and which contained a simple cannula linked to the centre of the re-entrant cannula. Each pig received two diets: diet A was based on wheat starch, sucrose and casein, while diet B was based on barley and soya-bean meal. The diets were given in equal amounts at 12 h intervals. Digesta and pancreatic juice were collected continuously during three 12 h periods for each pig on each diet. Mean duodenal output: dietary intake values for diets A and B respectively were: digesta 1.80, 2.86; dry matter 1.05, 1.03; nitrogen 1.05, 1.06; trichloroacetic acid (TCA)-soluble N 7.69, 9.10; glucose 0.97, 0.89. For diet A the proportion of TCA-soluble N in total N rose from 13 to 50% during 12 h, while it was approximately 50% throughout 12 h for diet B. Mean total pepsin (EC 3.4.23.1) activities (units/24 h) were 760449 (diet A) and 1 466 571 (diet B). Salivary and gastric secretions were calculated to be approximately 4 and 8 kg/24 h for diets A and B respectively. Mean flows in pancreatic juice (g/24 h) for diets A and B respectively were: juice 1204, 2182; protein 10.94, 12.10; N 1.98, 2.14; ash 9.46, 17.31; sodium 3.88, 6.91; potassium 0.23, 0.54; calcium 0.031, 0.046; phosphorus 0.024, 0.026. Mean total enzyme activities (units x 10(-3)/24 h) for diets A and B respectively were: trypsin (EC 3.4.21.4) 138, 114; chymotrypsin (EC 3.4.21.1) 84, 84; carboxypeptidase A (EC 3.4.2.1) 5, 4; carboxypeptidase B (EC 3.4.2.2) 15, 17; amylase (EC 3.2.1.1) 1061, 981. It was calculated that the minimum amount of endogenous N from saliva and gastric secretion was 0.3-0.6 g in 24 h. This assumes no absorption of N occurred anterior to the duodenal cannula.
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PMID:Studies on gastric digestion of protein and carbohydrate, gastric secretion and exocrine pancreatic secretion in the growing pig. 640 23

Elemental X-ray microanalysis of intact mouse peritoneal cells revealed significantly high K alpha sulfur and chloride peaks, while phosphorus, sodium and calcium displayed relatively low K alpha peaks. Bone marrow derived cultured mast cells exhibited a low K alpha peak for sulfur and a high K alpha peak for chloride. Peritoneal macrophages which served as controls differed from peritoneal mast cells by their high phosphorus and chloride content and a relatively low sulfur peak. The finding of two different spectra for the mast cells may provide additional parameters for discrimination of mast cell subsets.
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PMID:Elemental X-ray microanalysis of mouse peritoneal and bone marrow derived cultured mast cells. 674 27

In patients with chronic renal failure treated by long-term dialysis, inflammatory reactions occasionally develop in the bulbar conjunctiva; the episcleral tissue is only rarely involved. Diffuse congestion of both the conjunctiva and episclera was present in 5.3% of our patients and was associated with a sudden, marked rise in serum calcium. Histopathological examination suggests that this form of hyperemia, clinically preceded by a marked shedding of calcific precipitates, is the result of a neurogenic-driven inflammatory reaction in which mast cell degranulation is mediated by the axon reflex. Focal hyperemia associated with elastosis ("pingueculitis") was present in 6.7% of the patients. This type of hyperemia was observed after an extended period of increasing levels of BUN and seemed independent of both serum calcium and phosphorus. Diffuse hyperemia of the conjunctiva, being clinically distinctly different from the combined diffuse conjunctival and episcleral hyperemia, was also observed in 6.7%. Diffuse conjunctival hyperemia seemed to be associated with low BUN. Here, again, there was no association with serum calcium and phosphorus levels.
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PMID:The role of serum calcium in the development of the acute red eye in chronic renal failure. 779 5

Mast cells derived from the bone marrow of BALB/mice (BMMC) were cultured and their growth ceased with sodium butyrate. Sodium butyrate treatment (1mM, 4 days) caused maturation of the granules, an increased histamine content from approx. 1 pg/cell to 4 pg/cell. X-ray microanalysis revealed that maturation of the granules was accompanied by the increase in relative weight percent of sodium, phosphorus and sulphur, with concomitant decrease in chloride. The sulphur to potassium ratio increased three-fold in butyrate-treated mast cells. The existence of a different elemental composition during mast cell maturation may provide additional parameter for rapid discrimination of mast cell subpopulations.
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PMID:Effect of sodium butyrate treatment on the granule morphology, histamine level and elemental content of the bone marrow-derived mast cell. 802 97

A series of phosphonamidate compounds with different P1' amino acid residues have been shown to be irreversible inactivators of the serine beta-lactamase from Enterobacter cloacae P99. The efficiency of inhibition (based on k2/K values) of P99 by these derivatives, ordered in decreasing potency, is: beta-phenyl-beta-Ala > L-Phe > beta-Ala > Gly > D-Phe > D-Pro > D-thiazolidine. The D- and L-Phe compounds also inhibit carboxypeptidase A. The proline and thiazolidine derivatives were phosphonamidate methyl esters, whereas the others were salts of diacids. Electrospray mass spectrometry showed that equimolar mixtures of the P99 enzyme with each of the following derivatives, Gly, D-Phe, L-Phe, beta-Ala and beta-phenyl-beta-Ala, effected efficient adduct formation (70-95% of enzyme modified), illustrating the particularly active nature of some of these compounds. All the primary amino acid derivatives gave a similar mass increment, which suggests the displacement of the variable P1' part of the molecule. This observation provides evidence that the compounds phosphonylate the active-site serine, with the phosphonamidate bond as the scissile bond and the amino acid as the leaving group. The thiazolidine derivative (phosphonamidate methyl ester) also appeared to work by the same mechanism. The comparable proline derivatives caused lower than expected mass shifts of 227-229, and therefore it is proposed that with these compounds both the amino acid and the phosphonamidate ester methoxy group were displaced at the phosphorus atom during the inhibition process. Therefore, electrospray mass spectrometry has provided both a measure of potency and a rationale for the mechanism of inhibition of P99 by these compounds.
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PMID:Phosphonamidate analogues of dipeptides with carboxypeptidase A and beta-lactamase-inhibitory activity: elucidation of the mechanism of beta-lactamase inhibition by electrospray mass spectrometry. 867 57

The objective of this study was to investigate the relationship between protein nutrition, the pathophysiology, and acquisition and expression of immunity in long-term subclinical intestinal parasitism in sheep. Growing sheep were either uninfected controls or parasitised for 27 weeks with a daily dose of 2500 larvae of Trichostrongylus colubriformis, whilst they were given access to: (1) a low protein food, (2) a high protein food, or (3) a choice between the two foods, where they were allowed to select their diet. Blood samples were taken weekly for determination of serum albumin, total protein, Ca, P, urea and fructosamine concentrations. At the end of the study all sheep received a single (secondary) challenge infection (30,000 T. colubriformis L3) after treatment with anthelmintic to assess their immune status. The concentrations of sheep-mast cell proteinases (SMCP) in intestinal tissue, the number of circulating eosinophils and the total worm numbers recovered from the intestinal tract were used to investigate the effects of previous nutrition on the acquisition and expression of immunity. From the biochemical variables measured over 27 weeks, only serum fructosamine was affected by the interaction between feeding treatment and parasitism: fructosamine concentrations declined only in the parasitised animals on the low protein food during Weeks 6-15 of infection. This casts doubt on the usefulness of plasma fructosamine levels as an indicator of gastrointestinal parasitism, due to its being influenced by the nutritional environment. Total protein, albumin, calcium and phosphorus concentrations in the serum were affected by parasitism, but independently of feeding treatment. During the period of secondary challenge eosinophil numbers and SMCP concentrations were higher in the parasitised animals, reflecting the animals immune responsiveness. The numbers of worms recovered from the intestine of previously parasitised sheep were low; all three indicators of the development of acquired immunity were unaffected by previous nutritional treatment of the sheep. The results do not support the view that the pathophysiology of long term subclinical intestinal parasitism and the expression of acquired immunity induced by a trickle infection could be affected by the feeding treatment of the sheep (protein nutrition).
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PMID:The pathophysiology and development of immunity during long-term subclinical infection with Trichostrongylus colubriformis of sheep receiving different nutritional treatments. 891 99


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