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)

The effects of protein supplementation and infection with Trichostrongylus colubriformis on production responses and immune function in young sheep and on nematode population dynamics were assessed. Eighty-four 3-month-old Merino wether sheep were housed in individual pens and fed ad libitum chopped oaten hay containing 0.5% urea, together with 50 g day-1 lucerne meal. Fish meal (FM) was given as a source of protected protein at 0, 50 or 100 g day-1 (FM0, FM50, FM100; from Days --28 to 140). From Days 1 to 140, 0 or 1000 T. colubriformis infective larvae were given on Mondays, Wednesdays and Fridays. Infected sheep were slaughtered after 35, 70, 105, or 140 days of infection. Live-weight gain was reduced significantly by infection with T. colubriformis in sheep given FM0, but not in sheep given FM50 or FM100. Greasy wool production and fibre diameter were increased by FM, whereas the effects of infection with T. colubriformis on wool measurements depended on the level of FM given. Worm egg concentrations in faeces were significantly lower for sheep given FM100 than for those given FM0 or FM50 during the last 28 days of infection. Similarly, the apparent rate of worm expulsion was considerably higher in sheep given FM than in those not given FM. The rate of expulsion of T. colubriformis correlated with levels of circulating eosinophils as well as with the concentration of intestinal sheep mast cell proteases. Levels of parasite-specific and non-specific circulating antibodies were either unaffected or reduced as a result of supplementation with FM, although lymphocyte stimulation in vitro in response to T. colubriformis third stage larval antigen was enhanced significantly in infected animals given FM100. It was concluded that supplementary feeding with FM substantially reduced the production losses attributable to infection with T. colubriformis and was associated with enhanced expulsion of the parasite burden.
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PMID:Effects of dietary protein intake on responses of young sheep to infection with Trichostrongylus colubriformis. 773 40

Dietary proteins are degraded by both endogenous enzymes and the caecal microflora. In conventional rats the enzyme content of the pancreas depends on the amount of dietary protein. The influence of the caecal microflora on this process is unknown. We report here the effect of the caecal microflora on pancreatic enzymes (proteases, amylase (EC 3.2.1.1), lipase (EC 3.1.1.3)) and on colonic metabolites (NH3, urea, short-chain fatty acids). Germ-free and conventional male Fischer rats were fed for 3 weeks with a diet containing 220 or 450 g protein/kg provided as a mixture of fish concentrate and soyabean isolate. The excretion of NH3 and the pH were specifically increased by the high-protein diet in the germ-free rats. The higher production of isobutyrate, valerate and isovalerate in conventional rats fed on the high-protein diet reflected a high bacterial proteolytic activity since these short-chain fatty acids are specific indicators of this activity. The microflora hydrolysed urea to NH3 and maintained the pH at neutrality whatever the amount of protein in the diet since there were changes in germ-free rats but not in conventional ones. In germ-free rats, amylase, trypsin (EC 3.4.21.4), elastase (EC 3.4.21.36) and carboxypeptidase A (EC 3.4.17.1) specific activities were significantly lower than in conventional rats. The adaptation of the pancreas to the 450 g protein/kg diet was not impaired by the bacterial status except for the specific activity of chymotrypsin (EC 3.4.21.1) which was more increased by this diet in germ-free than in conventional rats. Moreover, the specific activity of lipase increased only in conventional rats fed on the 450 g protein/kg diet. In conclusion, we observed a relationship between the enzyme content of the pancreas and the presence or absence of the caecal microflora suggesting that bacterial fermentation influences pancreatic function.
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PMID:Influence of caecal microflora and of two dietary protein levels on the adaptation of the exocrine pancreas: comparative study in germ-free and conventional rats. 878 16

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

Pea proteins have been considered for the introduction into the human diet only recently. This protein source was tested on nutritional and digestive parameters in heteroxenic male Fischer rats inoculated with a human faecal microflora from a methane producer. Compared to soybean proteins, pea proteins have similar effects on the rat's endogenous and bacterial digestive patterns. Compared to the pea proteins, a diet containing a standard meat meal enhanced the pH and the production of ammonia, while a lyophilized beef meat enhanced that of urea. The diet containing the standard meat decreases short-chain fatty acids and modifies the ratio of caecal short-chain fatty acids. Both animal diets decreased the specific activities of pancreatic proteases such as chymotrypsin (EC 3.4.21.1), trypsin (EC 3.4.21.4), and carboxypeptidase A (EC 3.4.17.1) when compared to the diet containing the pea isolate. In conclusion, the whole composition of the diet, more than the origin of the dietary protein, influences the rat's digestive pattern.
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PMID:Physiological effects of a pea protein isolate in gnotobiotic rats: comparison with a soybean isolate and meat. 952 65

A new series of 1-(6-amino-9H-purin-9-yl)-1-deoxy-N-ethyl-beta-D-ribofuranuronamide++ +-b earing N-arylureas or N-arylcarboxamido groups at the purine 6 position and N-arylureas combined with halogens or alkynyl chains at the 2 position have been synthesized and tested for affinity at A1 and A2A adenosine receptors in rat brain membranes and at cloned rat A3 receptors expressed in CHO cells. The derivatives contained the 5' substituent found in the potent, nonselective agonist 1-(6-amino-9H-purin-9-yl)-1-deoxy-N-ethyl-beta-D-ribofuranuronamide++ + (NECA). While the carboxamido derivatives (9-13) showed affinity for A1 receptors, the urea derivatives (30-45) showed different degrees of affinity and selectivity for the A3 adenosine receptor subtype. In particular the derivative bearing a p-sulfonamidophenyl-urea at the 6 position, 31 showed a high affinity (Ki = 9 nM) and selectivity for the A3 receptors compared to that of the reference compound 1-[6-[[(3-iodophenyl)methyl]amino]-9H-purin-9-yl]-1-deoxy-N-methyl-be ta-D-ribofuranuronamide (IB-MECA). Furthermore, the importance of the stereochemistry in the interaction of these ligands at the rat A3 adenosine receptors has been evaluated by introducing a chiral chain at the 6 position. The introduction of halogens or alkynyl chains at the purine 2 position of selected ureas did not give the expected enhancement of potency at A2A and/or A3 receptors but rather showed a dramatic reduction of A2A affinity, resulting in compounds with good A2A/A3 selectivity. For example, the 2-(3-hydroxy-3-phenyl-1-propyn-1-yl)-6-(4-methoxyphenylurea) derivative 61 showed the capability to bind simultaneously to A1 and A3 receptor subtypes, excluding the A2A receptor. Compound 31 was shown to be an agonist, 9-fold more potent than NECA, at A3 receptors in rat RBL-2H3 mast cell membranes through stimulation of binding of [35S]GTP-gamma-S.
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PMID:Synthesis and biological activity of a new series of N6-arylcarbamoyl, 2-(Ar)alkynyl-N6-arylcarbamoyl, and N6-carboxamido derivatives of adenosine-5'-N-ethyluronamide as A1 and A3 adenosine receptor agonists. 970 63

Vaccination with a membrane-bound thiol Sepharose-binding fraction (TSBP) of adult Haemonchus contortus has been shown to confer significant levels of protection against homologous challenge in sheep. This fraction is greatly enriched for cysteine proteinase activity. Following fractionation of TSBP by anion-exchange chromatography on MonoQ, protection was found to partition with those fractions further enriched for cysteine proteinase activity. In this study, the cysteine proteinases of adult H. contortus TSBP were specifically purified by affinity chromatography using recombinant H. contortus cystatin, a potent cysteine proteinase inhibitor. Although only 1-1.5% of total TSBP bound to cystatin-Sepharose, this fraction contained 100% of the cysteine proteinase activity, as determined by gelatin substrate gel analysis. When used to immunise sheep, less than 3microg per dose of this cysteine proteinase fraction was found to confer a substantial and repeatable level of protection against homologous challenge infection, reducing faecal egg counts by 48 and 28% and worm burdens by 44 and 46% over two trials. Host serum immunoglobulin levels and abomasal mast cell and eosinophil numbers were evaluated, although no correlation with protection was observed. Three cathepsin B-like cysteine proteinases present in TSBP (hmcp1, 4 and 6) have been identified previously by cDNA library immunoscreening. The predicted mature forms of these three cysteine proteinases were expressed in bacteria as insoluble, GST-fusion proteins. Following solubilisation in urea/DTT, the protective capacity of a cocktail of recombinant proteins was evaluated in sheep. Although no reduction in faecal egg counts was observed, sheep vaccinated with recombinant cysteine proteinases showed a highly significant 38% reduction (P <0.01) in worm burdens.
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PMID:Protection studies in sheep using affinity-purified and recombinant cysteine proteinases of adult Haemonchus contortus. 1547 16

The predominant problems associated with peritoneal dialysis (PD) are ultrafiltration failure and peritonitis. PD maintains a state of intraperitoneal inflammation that affects the structure and function of the peritoneal membrane, potentially impairing ultrafiltration efficiency. Paradoxically, some PD fluids also have anti-inflammatory properties that may compromise the immune defense against peritonitis. This anti-inflammatory feature is mostly due to the glucose degradation products (GDPs), formed during heat-sterilization and storage of PD fluids. The main purpose of the present thesis was to study regulatory mechanisms behind the acute intraperitoneal inflammatory response in PD in the presence and absence of experimental peritonitis. Rats were exposed to a single dose of heat- or filter sterilized PD fluids either as an i.p. injection or as an infusion through an indwelling catheter, with or without supplementations, or pretreatment of the animals. The dwell fluid was analyzed zero, two and four hours later concerning activation of the complement and coagulation cascades, neutrophil recruitment and respiratory burst, ultrafiltration volumes, cytokine-induced neutrophil chemoattractant (CINC-1), rat mast cell protease 2 (RMCP-2), glucose, urea and histamine concentrations and ex vivo/in vitro intraperitoneal chemotactic activity. Exposure to filter sterilized PD fluid alone induced intraperitoneal complement activation and coagulation, neutrophil recruitment and increased the levels of CINC-1 during the dwell. Intraperitoneal concentrations of the mast cell markers histamine and RMCP-2 changed little during the dwells and did not indicate mast cell activation. Low molecular weight heparin (LMWH) and C5 blockade improved ultrafiltration. Pretreatment with cobra venom factor, known decomplementing agent, blocked the CINC-1 release and the neutrophil recruitment and improved ultrafiltration. In combination with experimental peritonitis, heat sterilized PD fluid compared to filter sterilized, inhibited the CINC-1 release and the recruitment of neutrophils to the peritoneal cavity without affecting the intraperitoneal complement activation. The results of the present thesis indicate that addition of LMWH to the PD fluid improves ultrafiltration, probably by blocking C5a activity. C5 blockade seems to improve ultrafiltration by a mechanism that involves a reduction in glucose transport, possibly by reducing C5 induced vasodilatation. Complement activation is an early step in the acute reaction to PD and probably mediates the downstream events that lead to the recruitment of inflammatory cells to the peritoneal cavity. The cells involved in the release of CINC-1 later in this sequence are probably the mesothelial cells. During experimental peritonitis, heat sterilized PD fluids inhibited the neutrophil respiratory burst response of intraperitoneal neutrophils. Heat sterilized PD fluids also inhibit the recruitment of neutrophils to the peritoneal cavity by a mechanism independent of complement activation but probably depending on cytokine CINC-1 release during peritonitis.
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PMID:Acute inflammation in peritoneal dialysis: experimental studies in rats. Characterization of regulatory mechanisms. 1584 49

A subchronic toxicity study of water pepper extract (WPE) from Polygonum hydropiper L. was conducted in groups of 10 male and 10 female F344 rats fed powdered diets containing 0, 62.5, 250, 1000 or 4000 ppm concentrations for 13 weeks. Suppression of body weight gain due to decreased food consumption was observed in both sexes at 4000 ppm, and at autopsy, increase of relative weights was observed for the brain, liver, spleen, kidneys, and testes in these animals, suggestive of the reflection of the reduced body weights. At this dose, slight increases of blood urea nitrogen in both sexes and serum alanine aminotransferase, Na and Cl in females, were observed, suggestive of weak hepatic and renal toxicity, at least in females. The same females also exhibited slight decrease of red blood cells and haematocrit, slight increase of mean corpuscular volume and mean corpuscular haemoglobin, and minimal increase of splenic haemosiderin deposition, providing evidence of slight haemolytic anemia. On the other hand, enhanced accumulation of mast cells was observed in the mesenteric lymph nodes at 4000 ppm in males and 1000 and 4000 ppm in females. Considering the anti-anaphylactic properties of polygodial, a major constituent of WPE, the mast cell accumulation was concluded to be an adaptive change in response to the subchronic oral administration of WPE. Based on the present toxicity data, 1000 ppm was determined to be the no-observed-adverse-effect level, translating into 57.4 and 62.9 mg/kg/day for male and female rats, respectively.
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PMID:Subchronic toxicity study of water pepper extract in F344 rats. 1654 68

Cyanobacterial cyclopeptides: A series of analogues of the cyanobacterial cyclopeptide brunsvicamide A was prepared by effective solid-support-based total synthesis. Variations in stereochemistry revealed the importance of the D-lysine and the L-isoleucine residues for the substrate-competitive inhibitory activity of brunsvicamide A against carboxypeptidase A. The brunsvicamides are modified cyclopeptides from cyanobacteria, cyclised through the epsilon-amino group of a D-lysine unit. They are functionalised with urea groups and show potent carboxypeptidase inhibitory activities. In order to unravel the structural parameters that determine their activities, a collection of brunsvicamide analogues with varied amino acid structures and stereochemistries was synthesised by a combined solution- and solid-phase approach. Biochemical investigation of the compound collection for carboxypeptidase A inhibition revealed that the presence of D-lysine and L-isoleucine in the urea section is important for inhibition. It was found that brunsvicamide A is a substrate-competitive inhibitor of carboxypeptidase A. These findings are in agreement with the substrate specificity of the enzyme and were rationalised by computational studies, which showed the high relevance of the lysine stereochemistry for inhibitory activity.
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PMID:Synthesis and structure-activity correlation of a brunsvicamide-inspired cyclopeptide collection. 1936 Aug 7

Neurofibromatosis Type 1 (NF1) is a common autosomal dominant disease characterized by complex and multicellular neurofibroma tumors, and less frequently by malignant peripheral nerve sheath tumors (MPNSTs) and optic nerve gliomas. Significant advances have been made in elucidating the cellular, genetic, and molecular biology involved in tumor formation in NF1. Neurofibromatosis Type 1 is caused by germline mutations of the NF1 tumor suppressor gene, which generally result in decreased intracellular neurofibromin protein levels, leading to increased cascade Ras signaling to its downstream effectors. Multiple key pathways are involved with the development of tumors in NF1, including Ras/mitogen-activated protein kinase (MAPK) and Akt/mammalian target of rapamycin (mTOR). Interestingly, recent studies demonstrate that multiple other developmental syndromes (in addition to NF1) share phenotypic features resulting from germline mutations in genes responsible for components of the Ras/MAPK pathway. In general, a somatic loss of the second NF1 allele, also referred to as loss of heterozygosity, in the progenitor cell, either the Schwann cell or its precursor, combined with haploinsufficiency in multiple supporting cells is required for tumor formation. Importantly, a complex series of interactions with these other cell types in neurofibroma tumorigenesis is mediated by abnormal expression of growth factors and their receptors and modification of gene expression, a key example of which is the process of recruitment and involvement of the NF1(+/-) heterozygous mast cell. In general, for malignant transformation to occur, there must be accumulation of additional mutations of multiple genes including INK4A/ARF and P53, with resulting abnormalities of their respective signal cascades. Further, abnormalities of the NF1 gene and molecular cascade described above have been implicated in the tumorigenesis of NF1 and some sporadically occurring gliomas, and thus, these treatment options may have wider applicability. Finally, increased knowledge of molecular and cellular mechanisms involved with NF1 tumorigenesis has led to multiple preclinical and clinical studies of targeted therapy, including the mTOR inhibitor rapamycin, which is demonstrating promising preclinical results for treatment of MPNSTs and gliomas.
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PMID:Neurofibromatosis Type 1 and tumorigenesis: molecular mechanisms and therapeutic implications. 2004 23


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