Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0220723 (PCA)
 4,687 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ten male patients with cirrhosis of the liver (three with portacaval anastomosis [PCA]) and eight sex- and age-matched controls underwent an arginine infusion test followed by an intravenous glucose tolerance test. Plasma glucose and growth hormone (GH) levels were measured during a period of three hours. In the normal subjects, the peak GH response to arginine occurred 60 minutes after the start of the infusion and was followed by a progressive decline in GH concentration; dextrose injection resulted in a further rapid fall in GH concentration. In cirrhotic patients, both fasting and postarginine GH concentrations were significantly higher than in controls; in addition, the dextrose injection, after causing a transitory drop in plasma GH levels, resulted in a marked increase in plasma GH concentration. In the patients with PCA, the plasma GH increase after arginine and after dextrous was more marked. In these cirrhotic patients, the plasma GH levels correlated directly with the magnitude of the portal hypertension and inversely with the serum albumin concentration, suggesting that the abnormality of GH secretion was a reflection of the derangement in liver function.
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PMID:Altered control of growth hormone secretion in patients with cirrhosis of the liver. 48 48

Guinea pigs were sensitized by p-phenetidine (PT), 2-hydroxy-p-phenetidine (HPT) as well as by conjugates prepared by reacting PT and HPT with proteins in vitro. Sensitization was evaluated by delayed skin reactivity and in vitro antigen-induced lymphocyte proleferation. HPT and HPT-protein conjugates were found to be the most effective sensitizing agents. Reaginic antibodies could be raised in both guinea pigs and rabbits by immunizing with PT- and HPT-protein conjugates but not by PT and HPT alone: these PCA antibodies showed strong cross-reactivity and could be elicited equally well with either the PT- or HPT-protein derivatives. By contrast, no precipitating antibodies could be raised in either species even after repeated immunizations over a period of 4 months. Peripheral blood lymphocytes, from a few patients who gave a positive patch test with PT, could be stiumlated in vitro with phenacetin and to a lesser degree with PT and with a HPT-derivative of human serum albumin.
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PMID:Immunogenicity of p-phenetidine, 2-hydroxy-p-phenetidine and their protein conjugates in guinea pigs, rabbits and man. 85 31

1. The role of platelet-activating factor (PAF) and peptidoleukotrienes as putative mediators of some of the vascular changes triggered by antigen was investigated in rats passively sensitized with monoclonal anti-DNP (2,4-dinitrophenyl) IgE. 2. Lethal anaphylaxis with respiratory distress, systemic hypotension, detachment of the intestinal mucosa, leukopenia and extravasation of protein-rich plasma was observed after antigen challenge of rats sensitized with partially purified monoclonal IgE at concentrations of 15 mg protein kg-1. 3. Analysis of the peritoneal fluid obtained after i.v. challenge with DNP-BSA (bovine serum albumin) showed the presence of significant amounts of PAF (101 +/- 8 pg/rat), whereas this mediator was undetectable in control animals. Leukotriene D4 was the predominant peptidoleukotriene that could be recovered after antigen challenge, and showed an extremely high concentration (92 +2- 15 ng/rat) as compared to PAF levels. 4. Extravasation of protein-rich plasma was observed shortly after challenge and reached a maximum at 30 min. Treatment of animals with i.v. PCA 4248 (1-2 mg kg-1) and WEB 2086 (1 mg kg-1), two chemically unrelated compounds which are antagonists of the PAF-receptor, produced a significant reduction of the extravasation of protein-rich plasma. 5. The same degree of protection could be afforded by MK-886, an inhibitor of leukotriene biosynthesis. Combined treatment with WEB 2086 and MK-886 provided greater inhibition of protein-rich plasma extravasation than either compound alone. PCA 4248 was also found to inhibit in a dose-dependent manner the systemic hypotension observed upon DNP-BSA challenge.6. These data indicate that the lipid mediators PAF and peptidoleukotrienes are major effectors of the vascular disturbances observed in rat passive IgE-mediated anaphylaxis.
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PMID:The role of platelet-activating factor and peptidoleukotrienes in the vascular changes of rat passive anaphylaxis. 159 74

Chemically defined haptenic reagents and haptenic conjugates were synthesized for use in clinical skin testing. One series of reagents was based on the 1-phenyl-2,3-dimethyl-3-pyrazolin-5-one structure, a second series on 1,2-diphenyl-pyrazolidine-3,5-dione. Haptens were connected via flexible spacer molecules which insert considerable distances between haptenic moieties and carriers. The skin test reagents were hexavalent conjugates prepared from the bis-penta-L-lysine carrier 'PAL'. The methodological details exemplify the application of N-hydroxysuccinimide activated ester derivatives for the preparation of peptidic conjugates. Rabbit and guinea-pig antisera against the haptens were obtained by immunization with human serum albumin conjugates. Efficacy and cross-reactivity relationships were assessed by guinea pig PCA and by testing actively immunized guinea pigs. A striking lack of cross-reactivity was found between pyrazolinone and pyrazolidinedione haptenic reagents in all test systems. On the other hand, the elicitation of homologous anaphylaxis was highly effective with the PAL conjugates. The data presented and discussed provide a basis for the evaluation of clinical tests performed in order to define drug-induced allergic reactions. They are relevant for immediate-type skin reactions as well as for serological methods.
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PMID:Defined test reagents for the diagnosis of drug-induced allergy. Antibody-dependent skin reactions towards pyrazolinone and pyrazolidinedione derivatives in the guinea pig. 361 98

The antigenicity or immunological characteristics of T-2588, newly-developed ester type cephem antibiotic, was studied employing rabbits, guinea pigs and mice. The results obtained were as follows: Antibody production against T-2588 was not observed in rabbit immunized with the emulsion of T-2588 and Freund's complete adjuvant (FCA). Hapten-specific antibody production against T-2525 was demonstrated by indirect hemagglutination test and 4 hrs. PCA of guinea pigs, employing rabbit antiserum hyperimmunized with the emulsion of T-2525 coupled to rabbit serum albumin and FCA. Hapten-specific antibody production against T-2525 was demonstrated by 48 hrs. PCA of rats, employing mice immunized with the mixture of T-2525 coupled to keyhole limpet hemocyanin and aluminium hydroxide gel. Cross antigenicity of T-2525 was observed to be relatively strong against cefotaxime and ceftizoxime, and very weak against cephalothin (CET), cefazolin, cefoperazone (CPZ), cefmenoxime, cefotiam and benzylpenicillin (PCG). Anaphylactic syndrome was not observed in guinea pigs actively sensitized with the emulsion of T-2588 or T-2525 and FCA. The ability of T-2588 and T-2525 to give a positive reaction in Coombs' test was rather weaker than that of CET, CPZ and PCG.
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PMID:[Immunological studies on the antigenicity of the cephem antibiotic T-2588]. 384 Feb 13

Multiple antibody components of rabbit antisera against p-azobenzenearsonate (R(p)) were studied with respect to their globulin nature and skin-sensitizing activity. IgA antibody was characterized by isolating two IgA-rich fractions from a specifically purified antibody preparation. Examination of these fractions showed that IgA antibodies existed in two molecular forms, one with a sedimentation constant of 7S and the other 9S. Skin-sensitizing activity was examined by a P-K type test and a PCA test with R(p)-rabbit serum albumin in homologous (rabbit) species. Only the 7S but not 9S IgA antibody sensitized rabbit skin. IgM antibody showed no activity and IgG antibody showed very low activity. In contrast, only IgG antibody was active in the P-K type test to sensitize a heterologous species (guinea pig). None of the antibodies of other classes showed sensitizing activity in heterologous skin. The 7S IgA antibody lost its sensitizing activity upon reduction and alkylation, although no change in its molecular size could be observed. The loss of sensitizing activity was not due to the destruction of antigen-binding activity since the treated 7S IgA antibody retained this activity as shown by radioimmunoelectrophoresis and by binding to the specific immunoadsorbent. The 9S IgA antibody was more resistant to these treatments than the IgM antibody and showed no indication of dissociation. The treated 9S IgA also retained antigen-binding activity. Both the P-K type and PCA reactions were considerably stronger when the interval between injections of antibody and antigen was 24 hr rather than 4 to 5 hr.
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PMID:Isolation of rabbit IgA antihapten antibody and demonstration of skin-sensitizing activity in homologous skin. 415 50

The effects of the different acyl side chains of azidocillin, ampicillin and benzylpenicillin on the immunogenic potency of penicilloylated antigens as well as on the specificity of the developed antibodies were investigated in CBA mice. The antigens used were penicilloylated bovine gammaglobulin (BGG), bovine serum albumin (BSA) and human serum albumin (HSA). Immunization was performed with injection of high doses of antigens together with adjuvant or by injection of minute amounts of antigen over periods of 10 days. IgE antibodies were recorded with PCA in rats and IgG antibodies were measured with a double antibody assay. The nature of the carrier as well as the number of epitopes was found to influence the development of antibodies irrespective of the immunization schedule used. The immunogenic activity of the PO-BSA antigens was related to the epitope density. The PO-BSA antigens were, in contrast to the PO-BGG antigens, weak immunogens in the CBA mice. The acyl side chains of the different penicillins influenced the induction and specificity of the IgE antibody responses obtained after daily treatment.
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PMID:Antigens in penicillin allergy. V. On the relative allergenic potency of antigens carrying penicilloyl determinants derived from azidocillin, ampicillin and benzylpenicillin. 615 79

Kinetics of primary and booster-specific and total IgE responses to distinct antigenic stimuli were studied in two inbred rat strains, Brown-Norway (BN) and Lewis, and one outbred, Sprague-Dawley (SD). The rats were immunized three or four times at intervals varying between 15 and 22 days by subcutaneous injections of 10 microgram ovalbumin, keyhole limpet haemocyanin (KLH) or bovine serum albumin (BSA) mixed with 10 mg aluminium hydroxide gel. IgE antibodies were measured in sera by PCA titres. High responses were obtained in BN rats (PCA titres about 10,000 after booster) and low responses in Lewis and SD rats. Positive booster responses were obtained in the three strains. Peritoneal mast cells collected from the three strains after immunization could degranulate on in vitro addition of specific antigen. In contrast, BN mast cells were bad receptors while Lewis and SD mast cells were good receptors for in vitro passive sensitization by mouse IgE antibodies. Total serum IgE was assayed by an in vitro competitive inhibition bioassay (CIB). The values before immunization were higher in BN (1-4 microgram/ml) than in Lewis (less than 0.25 microgram/ml) or SD rats (0.6 microgram/ml). After immunization, a striking increase could be observed in BN rats (up to 170 microgram/ml). There was no parallel between total IgE and IgE antibody levels at different times after immunization.
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PMID:Specific and total IgE responses to antigenic stimuli in Brown-Norway, Lewis and Sprague-Dawley rats. 696 9

The intravenous (i.v.) or oral administration of the platelet-activating factor (PAF) antagonist, PCA-4248, to guinea-pigs blocked selectively the bronchoconstriction induced by PAF, as well as the accompanying thrombocytopenia and leucopenia. In addition, PCA-4248 i.v. or intratracheal (i.t.) administration blocked the bronchoconstriction caused by the i.t. instillation of PAF. As in the case of other PAF antagonists, bronchoconstriction caused by the i.t. instillation of antigen was only inhibited by PCA-4248 in guinea-pigs that did not receive a booster injection of antigen during sensitization whereas the booster injection of antigen made anaphylactic bronchoconstriction resistant to the compound. In vitro, when lungs from non-sensitized guinea-pigs were perfused with Krebs-bovine serum albumin (BSA) solution supplemented with PCA-4248, bronchoconstriction and the formation of thromboxane A2 by PAF were blocked. In this in vitro model of perfused lungs, active sensitization with a booster injection of antigen leads to bronchopulmonary hyperresponsiveness to PAF and failure of other PAF antagonists to inhibit the effects of PAF itself. Surprisingly, in lungs isolated from actively sensitized and boosted guinea-pigs, PCA-4248 blocked the effects of PAF, indicating that this compound possesses additional original properties in this model.
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PMID:Compound PCA-4248 interferes with bronchopulmonary anaphylaxis and with in vitro hyperresponsiveness to platelet-activating factor. 768 2

The relation between islet cell specific antibodies, other autoantibodies and antibodies to cow's milk proteins was studied in IDDM and pre-IDDM by analysing islet cell antibodies (ICA), insulin autoantibodies (IAA), anti-nuclear (ANA), anti-reticulin class IgA [ARA(IgA)], smooth muscle, anti-mitochondria, parietal cell (PCA), adrenal and thyroid antibodies and antibodies to cow's milk formula (CMF), beta-lactoglobulin (BLG) and bovine serum albumin (BSA) in a population based study with more than 650 children with newly diagnosed IDDM and more than 550 initially non-diabetic siblings. After adjustment for age a weak association was seen in the diabetic children between IAA and ANA but none between ICA and autoantibodies directed against the other organ-specific or non-organ-specific antigens. There was no significant difference in cow's milk antibodies between diabetic children with and without ICA or IAA. The siblings with ICA had higher CMF (IgA and IgM) antibody levels and BLG (IgA) antibody levels than the remaining siblings, but no such differences were found when comparing IAA-positive and negative siblings. Siblings positive for ICA had PCA more often than did the ICA-negative siblings, whereas siblings positive for both ICA and PCA had increased levels of antibodies against CMF, BLG and BSA. These findings indicate that the humoral islet cell-associated autoimmunity characteristic of recent-onset childhood IDDM is clearly restricted to the islet cells and not directly related to signs of other organ-specific or non-organ-specific autoimmunity. The observation of increased levels of antibodies to cow's milk proteins in siblings positive for ICA suggests that the immune response to cow's milk proteins may be related to the progressive autoimmune process resulting in beta-cell destruction and ultimately in the clinical manifestation of IDDM. Gastrointestinal autoimmune mechanisms may play a role in the pathogenesis of IDDM, and the association observed between combined ICA and PCA positivity and increased levels of antibodies to cow's milk proteins in the siblings implies that there may be an enhanced transfer of nutritional antigens across the gut barrier in these subjects.
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PMID:Relation between antibodies to islet cell antigens, other autoantigens and cow's milk proteins in diabetic children and unaffected siblings at the clinical manifestation of IDDM. The Childhood Diabetes in Finland Study Group. 887 52


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