Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.10.1 (ERK)
 95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The paper examines the allergen specific B-cell response in peripheral blood from patients undergoing immunotherapy with house dust mite extract. The 12 patients were part of a double blind placebo controlled study, and they were treated with either Dermatophagoides pteronyssinus (n = 4), Dermatophagoides farinae extract (n = 3) (Alutard SQ, ALK, Denmark) or placebo (n = 5). Blood was taken every fortnight on day seven after hyposensitization and tested for IgM, IgG, IgA and IgE antibody secreting cells (AbSC) to D. pteronyssinus and D. farinae allergens and for the total number of immunoglobulin secreting cells (IgSC). The data showed a maximum of approximately 120 Der f I+II specific AbSC/10(6) mononuclear cells (MNC). A comparison of specific AbSC to the major allergens of the two house dust mites demonstrated that there was no measurable species specificity in the B-cell response that could be correlated to immunotherapy with either of the two extracts. The specific IgM, IgG, and IgA response to Der f I+II was examined in the placebo (39 measurements) and the actively treated (56 measurements) groups, and the results demonstrated a significant rise in specific IgM and IgA AbSC following immunotherapy. The number of specific IgG AbSC did not change. There was a mean of less than one specific IgE AbSC/10(6) MNC, and no detectable change following the treatment. It is speculated that immunotherapy to inhalant allergens causes the induction of specific IgA AbSC. It would then be these partly differentiated plasma cells that are detected on their way to the bronchial or gut mucosa to exert their protective function mediated by allergen specific secretory IgA.
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PMID:The allergen specific B-cell response during immunotherapy. 139 64

Two radioimmunoassays specific for cholecystokinin-like immunoreactivity (CCK-LI) in human tissue are described. The first assay employed an antiserum (Z-69) directed to the sulphated tyrosine at the C-terminal end of CCK-33 and measured all biologically active molecular forms of CCK except the controversial C-terminal tetrapeptide amide (CCK4). The sensitivity of this assay was 0.6 pmol/g. A second assay (employing antiserum Z-91) measured CCK-LI forms larger than the octapeptide and had a sensitivity of 0.2 pmol/g. Both assays were characterised with endogenous human peptides. Acid (pH 2.5) and neutral extracts (pH 6.5) of human intestine and brain were assessed for CCK-LI concentrations and gel chromatography performed in the presence of 6 mol/l urea to elucidate the various molecular forms. Human cerebral cortex CCK-LI was almost all sulphated CCK-8, but large molecular mass forms were present, particularly in acid extracts, forming about 10% of the whole. Human duodenum and jejunum contained approximately equal amounts of large CCK, CCK 33/39 and of CCK-8. Both intestine and brain possess not yet isolated sulphated molecular forms which eluted between the pure CCK-8 and CCK-33/39 standards. The results obtained from this study indicate that the biosynthesis of CCK in human brain and gut is quantitatively different.
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PMID:Measurement and characterisation of human cholecystokinin-like immunoreactivity (CCK-LI) in tissues by radioimmunoassay. 652 56

Norethisterone oenanthate (NET OEN) was extensively hydrolysed in rabbit, rat and guinea pig plasma (99.9%, 76.1% and 46.0% hydrolysed in 90 min, respectively). In contrast, there was negligible hydrolysis (less than 2.5%) in dog, goat and human plasma. Rabbit liver, kidney, gut wall, stomach, heart and muscle showed marked hydrolytic activity in vitro, but there was little hydrolysis of NET OEN by either human muscle or fat. It is proposed that following intramuscular administration of NET OEN to rabbits, the ester is rapidly hydrolysed at the injection site and in the circulation whereas in humans the liver is the main site of hydrolysis since neither muscle nor plasma cause significant breakdown of the ester. The rabbit is not a good model for predicting the pharmacokinetics of NET OEN in humans.
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PMID:Studies on the enzymatic cleavage of norethisterone oenanthate. 723 40

Cholecystokinin (CCK) is a gut hormone that regulates pancreatic endocrine functions via CCKA receptors. CCK4 (Trp-Met-Asp-Phe-NH2) has an insulinotropic effect, but is 1000-fold less potent than CCK8. The in vitro potencies and selectivity of newly synthesized CCK4 analogs were investigated. Exchanging various a amino acids, for example Met by Nle and modifying Phe and/or Trp, led to compounds that were much more effective than CCK4 itself and show insulinotropic effects comparable with those of CCK8. Compounds that possess electron withdrawing groups on the C-terminal phenylalanine were especially effective; compounds with electron-donating groups had no effect. In contrast to CCK8 the synthetic CCK4 compounds were selective for the endocrine pancreas: they had no agonistic or antagonistic effect on the contraction of the guinea pig ileum, amylase release from isolated acini, and no major effect on the feeding behavior of mice being supplied with either compound by an implantable AlzetR pump for 8 days. The data indicate that some of the synthetic tetrapeptides exhibit a high affinity for the CCK receptor of the endocrine pancreas and that they are highly selective for this (peripheral) CCKA receptor subtype. The beta-cell CCKA receptors are different from those in exocrine pancreas, smooth muscle, and those for regulating appetite; these peripheral receptor subtypes can be discriminated for the first time.
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PMID:Evidence for cholecystokinin receptor subtype in endocrine pancreas. 753 22

With Hyroxylapatite purified preparations and BACH (biotin aminocapryl hydrazide) biotinylated McAbs, 274-2H10 and 273-2H1, recognizing different egg-associated epitopes, biotin-avidin (BA) involved alkaline phosphatase (AP) ELISA with detecting sensitivities reaching nanogram levels (10(-9), were set up. The detectable limit for crude preparations of Schistosoma japonicum SEAJ-TCA in 2H10-ELISA achieved 1. 0.3. 2 ng/ml, in which only S. japonicum specific egg antigens were efficiently detected, whereas with 2H1-ELISA, which could detect SEA-TCA of both S. japonicum and S. mansoni species, an end point of detecting 3.2 ng/ml was obtained. Repeated tests with human serum groups revealed very significant differences of extinction OD readings between patients and normal individuals. For detection combinations, a previously established anti-CAA homologous AP-ELISA system was parallelly used for gut-associated antigenemia determinations. Taking the mean extinction OD reading of a parallel normal serum group plus 3 SD as corresponding cut off values, 3 patient groups (n = 82, 52, 39) from different areas of transmission intensity were subjected to accumulating determinations for egg- and gut-associated antigenemia. Improved detectabilities to variable extent were achieved in either of the 2 or 3 combinations. The study thus demonstrated that the diagnostic efficiency for human schistosomiasis could be improved by multi-epitope detections for more than one target molecule using corresponding McAbs, especially in areas where the transmission intensity of the disease is comparatively lower.
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PMID:[A preliminary report on diagnostic complementarity of gut-associated and egg-associated antigenemia in schistosomiasis japonica]. 754 May 18

c-RET is an orphan receptor tyrosine kinase essential for enteric neurogenesis in mice and is involved in several human genetic disorders. RET is also one of the earliest surface markers expressed by postmigratory neural crest cells in the gut. We generated anti-RET monoclonal antibodies to isolate such cells. We find that RET+ cells are antigenically and functionally distinct from neural crest stem cells (NCSCs) characterized previously. Unlike NCSCs, which are RET- and MASH1-, most RET+ cells express MASH1. Moreover, unlike NCSCs, which are multipotent and have high proliferative capacity, many RET+ cells generate only neurons following a limited number of divisions. This behavior is observed even in the presence of glial growth factor, a polypeptide that suppresses neuronal and promotes glial differentiation by NCSCs. These data provide direct evidence for the existence of committed neuronal progenitor cells and support a model of neural crest lineage diversification by progressive restriction of developmental potential.
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PMID:Postmigratory neural crest cells expressing c-RET display restricted developmental and proliferative capacities. 754 33

The protein superfamily of transmembrane receptor tyrosine kinases (RTKs) are essential components of intercellular signalling pathways necessary for normal cellular regulation. We report the cloning and developmental expression pattern of Nsk2, a novel, structurally distinct mammalian RTK characterised by a putative extracellular region bearing four immunoglobulin-like domains. The Nsk2 locus was mapped to the distal region of mouse chromosome 13 and was found to be expressed preferentially in skeletal muscle amongst adult mouse tissues. Moreover, increased steady-state levels of Nsk2 transcripts were apparent on terminal differentiation of committed skeletal myoblast cell lines in vitro and multiple isoforms of the Nsk2 RTK were identified in skeletal myotube cultures. RNA in situ hybridisation studies of mouse embryos confirmed skeletal myogenesis to be a major site of Nsk2 expression during normal embryogenesis, and identified other likely sites of Nsk2 function in ganglia of the developing peripheral nervous system and various embryonic epithelia, including those of kidney, lung and gut, during fetal development. Taken together, our data suggest normal functions for Nsk2 RTKs in distinctive aspects of skeletal muscle development, neurogenesis and mesenchymal-epithelial interactions during organ formation.
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PMID:Cloning and developmental expression of Nsk2, a novel receptor tyrosine kinase implicated in skeletal myogenesis. 762 44

Hirschsprung disease (HSCR), or congenital aganglionic megacolon, is the most common cause of congenital bowel obstruction with an incidence of 1 in 5000 live births. Recently, linkage of an incompletely penetrant, dominant form of HSCR was reported, followed by identification of mutations in the RET receptor tyrosine kinase. To determine the frequency of RET mutations in HSCR and correlate genotype with phenotype, we have screened for mutations among 80 HSCR probands representing a wide range of phenotypes and family structures. Polymerase chain reaction (PCR) and single-strand conformation polymorphism (SSCP) analysis of RET's 20 exons for mutations among probands revealed eight putative mutations (10%). Sequence changes, which included missense, frameshift and complex mutations, were detected in both familial and isolated cases, among patients with both long- and short-segment HSCR and in three kindreds with other phenotypes (maternal deafness, talipes and malrotation of the gut, respectively). Two mutations (C609Y and C620R) we identified have previously been associated with multiple endocrine neoplasia type 2A (MEN2A), medullary thyroid carcinoma (MTC) and, on rare occasions, HSCR. Thus, while HSCR family members may be at risk for developing neuroendocrine tumors, it follows that identical mutations in RET may be able to participate in the pathogenesis of distinct phenotypes. Our data suggest that: (i) the overall frequency of RET mutations in HSCR patients is low and therefore, other genetic and/or environmental determinants contribute to the majority of HSCR susceptibility, and (ii) at present, there is no obvious relationship between RET genotype and HSCR phenotype.
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PMID:Mutation analysis of the RET receptor tyrosine kinase in Hirschsprung disease. 763 41

Endopeptidase-24.11 (neutral endopeptidase, neprilysin, 'enkephalinase', EC 3.4.24.11) and endopeptidase-24.18 (endopeptidase-2, meprin, EC 3.4.24.18) are cell-surface zinc-dependent metallo-endopeptidases able to cleave a variety of bioactive peptides including growth factors. We report the first study of the cellular and tissue distribution of both enzymes and of the mRNA for NEP during embryonic development in the rat. Endopeptidase-24.11 protein was first detected at E10 in the lining of the gut and, at E12, the enzyme was present on the notochord, medial and lateral nasal processes, otocyst, mesonephros, heart and neuroepithelium. In contrast, at this time endopeptidase-24.18 was present only on the apical surface of the neuroepithelial cells. By E14 and E16, NEP was also detected in a wide range of craniofacial structures, notably the palatal mesenchyme, the choroid plexus, tongue and perichondrium. The distribution of endopeptidase-24.18 at these stages was restricted to the inner ear, the nasal conchae, and ependymal layer of the brain ventricles and the choroid plexus. Although endopeptidase-24.11 had been detectable in the craniofacial vasculature at E12 and E14, this was no longer apparent at E16. Significantly, the distribution of endopeptidase-24.11 mRNA closely matched the immunolocalization of the protein at all stages investigated. In order to explore the functional role of these enzymes, inhibition studies were carried out using two selective inhibitors of endopeptidase-24.11, phosphoramidon and thiorphan. E9.5 and E10.5 embryos exposed to either inhibitor displayed a characteristic, asymmetric abnormality consisting of a spherical swelling, possibly associated with a haematoma, predominantly on the left side of the prosencephalon, and the severity of this defect appeared to be a dose-dependent phenomenon. This study suggests that these enzymes play previously unrecognized roles during mammalian embryonic development.
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PMID:Distribution of, and a putative role for, the cell-surface neutral metallo-endopeptidases during mammalian craniofacial development. 772 May 64

The RET proto-oncogene encodes a receptor tyrosine kinase. We and others have recently shown that distinct germline mutations of the RET proto-oncogene account for the majority of cases of the dominantly inherited multiple endocrine neoplasia (MEN) type 2 syndromes, and can cause a dominantly inherited form of Hirschsprung disease, a disorder of development of the autonomic innervation of the gut. RET is also oncogenically activated in some sporadic thyroid and adrenal tumours. Here we report the characterisation of multiple mRNA isoforms of RET generated by alternate splicing. Two isoforms are predicted to encode membrane-spanning receptors with a truncated extracellular ligand-binding domain. A third isoform is predicted to encode a soluble, secreted form of the receptor. These mRNA isoforms are expressed in both normal and tumour tissues.
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PMID:Multiple mRNA isoforms of the human RET proto-oncogene generated by alternate splicing. 773 89


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