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)

A high-performance liquid chromatography method for analyzing disaccharides derived from chondroitin sulfate glycosaminoglycans has been developed which employs a Whatman Partisil-10 PAC amino-cyano column and an acetonitrile/methanol/ammonium acetate solvent to resolve disulfated, monosulfated, and unsulfated disaccharides in a chromatographic run of less than 20 min. The single known trisulfated chrondroitin disaccharide can be eluted in an alternate solvent system containing the same mobile phase components in different proportions. Disaccharides were prepared for chromatography from glycosaminoglycans and proteoglycans of known compositions by digestion with chondroitinase ABC, with the exception of king crab cartilage glycosaminoglycan which was incubated sequentially with hyaluronidase and chondroitinase ABC. Disaccharides were extracted from the digestion mixtures in 80% ethanol, dried over nitrogen, resuspended in the HPLC solvent, and chromatographed at a flow rate of 1 ml/min. Unsaturated disaccharides in the column eluate were detected by continuous ultraviolet absorbance monitoring at 232 nm; alternatively, fractions were collected and assayed for uronic acid content or radioactivity. By utilizing the HPLC technique in conjunction with chondroitinase ABC and AC digestion and sulfatase hydrolysis, the epimeric structures of chondroitin sulfates E and H were confirmed. With this technique, rapid and reproducible analyses of chondroitin sulfate disaccharides generated from mouse mast cell proteoglycan and from glycosaminoglycans of squid cranial cartilage, shark skin, hagfish skin, and hagfish notocord were in close agreement with compositions obtained by other techniques.
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PMID:Analysis of polysulfated chondroitin disaccharides by high-performance liquid chromatography. 643 72

Stimulation of the anticoagulation system with the structural analogs of alpha-thrombin, DPP-alpha-thrombin and prothrombin I having no proteolytic activity leads, as is the case with alpha-thrombin, to a decrease in the heparin content in mast cells and to a concurrent rise in the blood level of the complex compounds of heparin and blood proteins. Morphometry disclosed a substantial shift of mast cell population towards the light, heparin-free forms. In the experimental animals, the index of mast cell saturation with heparin dropped below one. Heparin release by mast cells proceeded by the merocrine secretion type, largely at the expense of granulolysis, with the cell integrity being preserved. Degranulation was effected via the strong form. Intravenous injection to the animals of alpha-thrombin in the presence of the anticoagulation system blockade with chlorpromazine produced no similar changes in the mast cell population.
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PMID:[Analysis of the mast cell population in excitation and blockade of the anticoagulant system]. 711 21

PAC spectra (perturbed angular correlation of gamma-rays) of cadmium-substituted carboxypeptidase A (CPD) show that the enzyme in solution imposes a flexible, pH- and chloride-dependent coordination structure on the metal site, in contrast to what is found in the crystalline state. A much more restricted coordination geometry occurs for the steady-state peptide intermediates of Bz-Gly-l-Phe and Bz-Gly-Gly-l-Phe in solution, suggesting that substrate binding locks the structure in a rigid conformation. The results further indicate that the peptide intermediate has a six-coordinated metal coordination geometry with an OH- ligand at the solvent site and a carbonyl oxygen at an additional ligand site. In marked contrast, conformational rigidity is not induced by the inhibitor/poor substrate Gly-L-Tyr nor by the products of high turnover substrates, Bz-Gly, Bz-Gly-Gly, and L-Phe. These results are consistent with an intact scissile peptide bond in the enzyme-substrate complex of Bz-Gly-L-Phe and Bz-Gly-Gly-L-Phe. A single nuclear quadrupole interaction (NQI) is observed for the crystalline state of the enzyme between pH 5.7 and pH 9.4. This NQI agrees with calculations based on the metal coordination geometry for cadmium in crystalline CPD derived from X-ray diffraction studies. A single broad distribution of NQIs is observed for CPD in sucrose solutions and 0.1 M NaCl at pH values below 6.5. This NQI (NQI-1') has parameters very close to those for the crystalline state. The enzyme metal site, characterized by this NQI, is converted into two new enzyme metal sites over the pH range of 6.5-8.3. The metal coordination sphere of one of these has a NQI (NQI-1) with parameters similar to those at lower pH values (NQI-1') while the other NQI (NQI-2) is characterized by markedly different NQI parameters. Angular overlap model (AOM) calculations indicate that the coordination sites giving NQI-1' and NQI-1 both have a metal-bound water molecule while the coordination site giving NQI-2 has a metal-bound hydroxide ion. PAC results at pH 8.3-10.5 indicate that in this pH range the two metal coordination geometries related to NQI-1 and NQI-2 occur in a pH independent ratio of 2:1, with the one with the water ligand being the most abundant species. The observed pH-independent equilibrium between the two different metal coordination geometries for cadmium can be explained by an equilibrium between tautomeric forms of a hydrogen bond between the Glu-270 carboxyl group and the metal-bound water (Glu-270 COO-...(HOH)M <==> Glu-270 COOH...(OH-)M) being slow on the time scale of a PAC experiment, i.e., slower than 0.5 micros. We finally suggest that NQI-1' observed at low pH reflects an enzyme species containing a metal-coordinated water molecule and the protonated carboxyl group of Glu-270.
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PMID:Structure and dynamics of the metal site of cadmium-substituted carboxypeptidase A in solution and crystalline states and under steady-state peptide hydrolysis. 929 72

Chymase, a major product of mast cell activation, is secreted as a fully active enzyme. We have prepared recombinant human prochymase and have investigated the conditions under which it may be activated by dipeptidyl peptidase I (DPP I). The gene for human chymase was cloned in a baculovirus vector and expressed in High Five insect cells, and the recombinant protein purified by heparin-agarose and gel-filtration chromatography. The purified prochymase was homogeneous by SDS/PAGE with the same molecular mass as native human chymase, and its identity confirmed by N-terminal sequence analysis and Western blotting with chymase-specific antibodies. Treatment with DPP I to remove the N-terminal dipeptide prosequence resulted in enzymatically active chymase, with substrate and inhibitor profiles very similar to those of the native human enzyme. The activation of prochymase by DPP I was strongly inhibited by heparin (IC50 = 0.5 microg ml[-1]) and histamine (IC50 = 2 mM), though these mast cell products had little effect on the action of DPP I towards a low molecular-mass substrate. The pH optimum of DPP I was also higher and narrower with prochymase. The inhibitory action of heparin was lost at NaCl or KCl concentrations sufficient to elute prochymase from a heparin agarose column. Dextran sulphate was as inhibitory as heparin, whereas chondroitin sulphate C was more than 10-fold less effective. Our findings suggest that the activation of prochymase might be restricted to the early stages of vesicle maturation, when the pH is close to neutrality and the histamine and heparin concentrations are low.
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PMID:The conversion of recombinant human mast cell prochymase to enzymatically active chymase by dipeptidyl peptidase I is inhibited by heparin and histamine. 957 89

It has been shown that activation of protein tyrosine kinases (PTKs) is the earliest detectable signaling response to FcepsilonRI cross-linking on mast cells. Following tyrosine kinase activation, a family of mitogen-activated protein kinases (MAPKs) was found to be activated as well. Activation of this PTK signaling cascade will lead to mast cell degranulation. This review summarizes our recent studies on the role of PTK signaling cascade in an in vitro guinea pig model of allergic asthma using PTK inhibitors, genistein and tyrphostin 47, and MAPK kinase inhibitor, PD098059. Inhibitors of the PTK and MAPK signaling pathways significantly attenuated the ovalbumin (OVA)-induced bronchial anaphylactic contraction and enhanced relaxation of constricted airways, respectively, and substantially blocked the release of histamine and peptidoleukotrienes from chopped lung preparations induced by OVA. Based upon their substantial inhibitory effects on the Schultz-Dale reaction, further examination on the potential anti-asthmatic effects of PTK cascade inhibitors in an in vivo model of allergic asthma is recommended.
Asian Pac J Allergy Immunol 1999 Sep
PMID:Effects of inhibitors of the tyrosine kinase signaling cascade on an in vitro model of allergic airways. 1069 63

It has been discussed in several studies that non-immunologic factors, such as renin angiotensin aldosterone system (RAAS) may play a role in the pathophysiology of anaphylaxis. This study aimed to determine whether RAAS plays a part in the fall in blood pressure during drug reactions or not. Twenty patients who experienced hypotension during drug reaction and 15 healthy volunteers were enrolled in this study. None of the patients in the study or control groups were under treatment with any drug that was capable of influencing to RAAS. Serum levels of angiotensin-I (A-I), angiotensin-II (A-II), angiotensin converting enzyme (ACE) and aldosterone were measured in both study and control groups. The Mann-Whitney U test was used to compare the results of the groups. There were no statistically significant differences between the groups with respect to A-I, A-II, ACE and aldosterone levels. It was concluded that a fall in blood pressure during drug reaction must be the result of mast cell mediator effects on the vascular wall rather than RAAS impairment.
Asian Pac J Allergy Immunol 2000 Jun
PMID:Renin angiotensin aldosterone system and drug allergies complicated with hypotension. 1092 19

The 8p11 myeloproliferative syndrome (EMS) is associated with three translocations, t(8;13)(p11;q12), t(8;9)(p11;q33), and t(6;8)(q27;p11), that fuse unrelated genes (ZNF198, CEP110, and FOP, respectively) to the entire tyrosine kinase domain of FGFR1. In all cases thus far examined (n = 10), the t(8;13) results in an identical mRNA fusion between ZNF198 exon 17 and FGFR1 exon 9. To determine if consistent fusions are also seen in the variant translocations, we performed RT-PCR on four cases and sequenced the products. For two patients with a t(8;9), we found that CEP110 exon 15 was fused to FGFR1 exon 9. For two patients with a t(6;8), we found that FOP exon 5 (n = 1) or exon 7 (n = 1) was fused to FGFR1 exon 9. To determine if FGFR1 might be involved in other myeloid disorders with translocations of 8p, we developed a two-color FISH assay using two differentially labeled PAC clones that flank FGFR1. Disruption of this gene was indicated in a patient with a t(8;17)(p11;q25) and Ph-negative chronic myeloid leukemia in association with systemic malignant mast cell disease, a patient with acute myeloid leukemia with a t(8;11)(p11;p15), and two cases with T-cell lymphoma, myeloproliferative disorder, and marrow eosinophilia with a t(8;12)(p11;q15) and ins(12;8)(p11;p11p21), respectively. For the patient with the t(8;11), the chromosome 11 breakpoint was determined to be in the vicinity of NUP98. We conclude that 1) all mRNA fusions in EMS result in splicing to FGFR1 exon 9 but breakpoints in FOP are variable, 2) two-color FISH can identify patients with EMS, and 3) the t(8;17)(p11;q25), t(8;11)(p11;p15), t(8;12)(p11;q15), and ins(12;8)(p11;p11p21) are novel karyotypic changes that most likely involve FGFR1.
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PMID:Identification of four new translocations involving FGFR1 in myeloid disorders. 1155 Feb 83

Atopic ocular diseases involve a spectrum of immuno-inflammatory responses. There are minimal pathologic changes with SAC. With PAC, there is increased mast cell activation and late-phase inflammatory cell infiltrate as a consequence of continued allergic stimulation. Associated with the more chronic and severe forms of atopic ocular disorders, GPC, VKC and AKC, there is persistent mast cell, eosinophil, and lymphocyte activation resulting in pathologic changes. Therapeutic intervention for atopic ocular diseases has focused on symptomatic improvement. However, with an increasing understanding of the molecular mechanisms associated with the allergic inflammatory response, experimental studies may facilitate the development of preventative strategies.
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PMID:Atopic ocular disease. 1206 72

A prospective, cross-sectional and randomized cross-over study was conducted to study the clinical features and treatment outcome among Thai patients with vernal keratoconjunctivitis (VKC). History-taking and eye examinations were performed. Mild cases of VKC were given topical antihistamine four times daily. Moderate and severe cases of VKC were treated with topical lodoxamide four times a day. Severe cases of VKC were given topical corticosteroids. Moderate and severe cases of VKC, which were refractory to treatment with either corticosteroids or a mast cell stabilizer had topical cyclosporine 0.5% instilled four times daily. Five patients were exposed to two different treatment regimens in sequence. As main outcome measures, itching, foreign body sensation, photophobia, conjunctival injection, papillae and chemosis were evaluated weekly. The patients with the palpebral type of VKC had daily symptoms, which were more severe and triggered by house-dust with a significant difference among the groups. Limbal VKC was associated with allergic rhinitis more commonly than palpebral VKC. Positive results of skin prick testing to acacia, careless weed, mold, Johnson grass and cow's milk were significantly more common in patients with palpebral VKC. The most common symptoms and signs were found in the mixed type of VKC. Purulent discharge, pannus and lid erythema were found in the palpebral type. Levocabastine hydrochloride was sufficient for mild cases of limbal VKC; lodoxamide for the limbal and mixed types. Prednisolone acetate was the drug of choice in severe cases of any type but only for a short period of time. The success rate of topical cyclosporine in the palpebral type was lower than in the limbal type due to an intolerable burning sensation. Topical cyclosporine used in 4 patients with limbal and palpebral type had a success rate of 100% which was greater than in the lodoxamide group (66.7%, 0%). Compared with topical corticosteroid-treated eyes in one patient, the success rate in topical cyclosporine-treated eyes was not success. Grading the severity of each type of VKC is crucial to obtain good response of any medication and compliance. Topical cyclosporine 0.5% can be an alternative drug to relieve symptoms and signs of VKC in order to avoid steroid-induced glaucoma.
Asian Pac J Allergy Immunol 2003 Mar
PMID:Vernal keratoconjunctivitis in Thailand. 1293 48

Ocular allergic disorders can be a component of systemic or local allergies. The importance of ocular allergy results from its incidence rather than from its severity, however, some of them are vision-threatening. The majority of ocular allergies affect the conjunctiva, eyelids and sometimes cornea that is exposed to the environment and is the place of interaction between allergens and immunocompetent cells. Different types of allergic disorders in the eye may have similar signs and symptoms, but each has its own pathognomonic characteristics, which help to diagnose, differentiate and choose the most suitable therapy. Ocular allergic diseases are classified into six categories: SAC, PAC, VKC, AKC, GPC and ConBC. In 2001 EAACI suggested new classification, also of allergic conjunctivitis, into IgE-mediated and non-IgE-mediated conjunctivitis. IgE-mediated conjunctivitis may be divided into intermittent and persistent conjunctivitis. Persistent allergic conjunctivitis is classified into vernal and atopic keratoconjunctivitis. Conjunctivitis contact allergy is a non-IgE form of allergic conjunctivitis. Currently available medications provide safe and effective management of most cases of ocular allergy. Drugs used in the treatment of ocular allergic disorders include mast cell stabilizers, antihistamines, steroids, NSAID's, artificial tears and others.
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PMID:[Clinical picture, diagnosis and therapy of allergic eye diseases]. 1452 17


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