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S Ullrich

Publications and source records attributed to S Ullrich.

67 records · Page 4Linked to original sources
PubMed1988

GTP-dependent inhibition of insulin secretion by epinephrine in permeabilized RINm5F cells. Lack of correlation between insulin secretion and cyclic AMP levels.

The mechanism by which alpha 2-adrenergic agonists inhibit exocytosis was investigated in electrically permeabilized insulin secreting RINm5F cells. In this preparation alpha 2-adrenoceptors remain coupled to adenylate cyclase, since basal- and forskolin-stimulated cyclic AMP production was lowered by epinephrine and clonidine by 30-50%. Cyclic AMP levels did not correlate with the rate of insulin secretion. Thus, at low Ca2+, forskolin enhanced cyclic AMP levels 5-fold without eliciting secretion, and Ca2+-stimulated secretion was associated with decreased cyclic AMP accumulation. Epinephrine (plus propranolol) inhibited Ca2+-induced insulin secretion in a GTP-dependent manner. The maximal inhibition (43%) occurred at 500 microM GTP. Clonidine also inhibited Ca2+-stimulated secretion. Replacement of GTP by GDP or by the nonhydrolyzable GTP analog guanosine 5'-(3-O-thio)triphosphate as well as treatment of the cells with pertussis toxin prior to permeabilization abolished epinephrine inhibition of insulin secretion. Pertussis toxin did not affect Ca2+-stimulated secretion. Insulin release stimulated by 1,2-didecanoyl glycerol was also lowered by epinephrine suggesting an effect distal to the activation of protein kinase C (Ca2+/phospholipid-dependent enzyme). These results taken together with the ability of epinephrine to inhibit ionomycin-induced insulin secretion in intact cells suggest that alpha 2-adrenergic inhibition is distal to the generation of second messengers. A model is proposed for alpha 2-adrenoceptor coupling to two effector systems, namely the adenylate cyclase and the exocytotic site in insulin-secreting cells.

Adenylate Cyclase Toxin↗
PubMed1988

Specific interaction between a subset of the p53 protein family and heat shock proteins hsp72/hsc73 in a human osteosarcoma cell line.

We report here immunological evidence for the specific association between p53 and hsp72/hsc73 heat shock proteins in a human cell line derived from an osteosarcoma. The same association between p53 and hsp72/hsc73 was observed in HOS-TE85 clone 5 from which the HOS-SL cell line was derived. This association was indicated by the co-immunoprecipitation from HOS-SL of both p53 and hsp72/hsc73 proteins observed with either an anti-p53 monoclonal antibody (PAb421) or an antiserum specifically reacting with hsp72/hsc73 heat shock proteins. Furthermore, Western blot analysis allowed us to show that hsp72/hsc73 proteins did not share an epitope with p53, confirming that the co-immunoprecipitation of p53 and hsp72/hsc73 was attributable to the physical association of the proteins. Data obtained from SDS-PAGE show that the HOS-SL cells expressed two forms of p53 with distinct molecular weights. Both forms contained several species with different isoelectric points ranging between pH 6.0 and 6.5. The data obtained from both 1D and 2D gel analyses consistently show that the p53 proteins involved in the association with hsp72/hsc73 were mainly the species that migrated with the slower mobility in the SDS dimension. The possibility is discussed that the HOS-SL p53 variant forming a complex with hsp72/hsc73 contains an activating mutation for transformation.

Antibodies, Monoclonal↗
PubMed1987

Regulation of exocytosis in electrically permeabilized insulin-secreting cells. Evidence for Ca2+ dependent and independent secretion.

The regulation of insulin secretion from RINm5F cells exposed to high voltage discharge has been investigated. Electron microscopy revealed that the overall structure of the cells was preserved after permeabilization. In this preparation insulin release was stimulated by Ca2+ (EC50 = 2.4 microM). The stable GTP analogue GTP gamma S enhanced secretion both at intermediate (nano- to micromolar) and vanishingly low (less than 10 pM) Ca2+ concentrations. At optimal Ca2+ (10 microM) the effect of GTP gamma S was greatly reduced. We investigated whether the secretory response to GTP analogues was mediated by any of three enzyme systems regulated by GTP-binding proteins, i.e. generation of cyclic AMP by adenylate cyclase, of diacylglycerol by phospholipase C and of arachidonic acid by phospholipase A2. The involvement of these messenger systems could be excluded as (i) cyclic AMP only had minor, Ca2+ dependent effects, (ii) phospholipase C was not activated in the absence of Ca2+ and insulin secretion due to the phorbol ester TPA displayed a different Ca2+ dependency, (iii) arachidonic acid did not elicit Ca2+ independent insulin secretion. These results, taken together with the finding that insulin secretion due to Ca2+ or TPA is attenuated by the inhibitory guanine nucleotide GDP beta S, suggest the existence of a regulatory site in exocytosis which is sensitive to guanine nucleotides.

Animals↗
PubMed1985

Quinine inhibits Ca2+-independent K+ channels whereas tetraethylammonium inhibits Ca2+-activated K+ channels in insulin-secreting cells.

The effects of quinine and tetraethylammonium (TEA) on single-channel K+ currents recorded from excised membrane patches of the insulin-secreting cell line RINm5F were investigated. When 100 microM quinine was applied to the external membrane surface K+ current flow through inward rectifier channels was abolished, while a separate voltage-activated high-conductance K+ channel was not significantly affected. On the other hand, 2 mM TEA abolished current flow through voltage-activated high-conductance K+ channels without influencing the inward rectifier K+ channel. Quinine is therefore not a specific inhibitor of Ca2+-activated K+ channels, but instead a good blocker of the Ca2+-independent K+ inward rectifier channel whereas TEA specifically inhibits the high-conductance voltage-activated K+ channel which is also Ca2+-activated.

Adenoma, Islet Cell↗
PubMed1985

Expression of both alpha 1- and alpha 2-adrenoceptors in an insulin-secreting cell line. Parallel studies of cytosolic free Ca2+ and insulin release.

Changes in intracellular free Ca2+, [Ca2+]i, and immunoreactive insulin release in response to alpha-adrenergic agents were measured in RINm5F cell suspensions. Cells were loaded with the fluorescent indicator quin 2 for monitoring [Ca2+]i. Epinephrine (1 microM), which inhibited alanine-stimulated insulin release by 73%, evoked a transient rise in [Ca2+]i. This rise is in part due to Ca2+ mobilization, since it is still present in the absence of extracellular Ca2+. The alpha 2-adrenergic agonist clonidine (10 microM) mimicked the epinephrine effect on insulin release without any change in [Ca2+]i. In contrast, the alpha 1-adrenergic agonist phenylephrine (10 and 100 microM) raised [Ca2+]i, albeit to a lesser extent than epinephrine. Phenylephrine enhanced basal, but had no effect on alanine-stimulated insulin release. To examine further the nature of the effect of epinephrine, specific alpha-adrenergic blocking agents were employed. The epinephrine-induced increase in [Ca2+]i could be inhibited by the alpha 1-adrenergic antagonists BE2254 (0.1 microM) and prazosin (0.01 microM). In the presence of these blockers, epinephrine was still able to inhibit insulin release. When alpha 2-adrenergic receptors were blocked by the addition of idazoxan (0.1 and 1 microM), epinephrine still raised [Ca2+]i. At the higher concentration of idazoxan, the epinephrine inhibition of insulin release was completely overcome. The alpha-adrenergic agonists did not attenuate the alanine-induced rise in [Ca2+]i. This study shows that both subtypes of alpha-adrenergic receptors are present in the insulin-secreting cell line RINm5F. The activation of alpha 1-adrenergic receptors leads to an increase in [Ca2+]i. In contrast, the inhibition of insulin release due to epinephrine is mediated through alpha 2-adrenergic receptors. The alpha 2-adrenergic mechanism does not involve changes in [Ca2+]i, but is rather exerted at a later step in the secretory process.

Alanine↗
PubMed1984

Glyceraldehyde, but not cyclic AMP-stimulated insulin release is preceded by a rise in cytosolic free Ca2+.

The dynamics of changes in membrane potential, cytosolic free Ca2+, [Ca2+]i and immunoreactive insulin release were assessed in RINm5F cells. Membrane depolarization and a rise in [Ca2+]i preceded the stimulation of insulin release by D-glyceraldehyde. Forskolin, which raised the cellular cyclic AMP levels, stimulated insulin release without changing membrane potential or [Ca2+]i. It is concluded that cyclic AMP acts on insulin release not by mobilizing Ca2+ but by another, as yet undefined, mechanism.

Aminoquinolines↗
PubMed1984

Islet cyclic AMP levels are not lowered during alpha 2-adrenergic inhibition of insulin release.

Epinephrine-induced changes in insulin release and cyclic AMP levels were measured simultaneously in isolated rat islets. Forskolin was used to enhance islet cyclic AMP levels. Forskolin (30 microM) stimulated adenylate cyclase activity 10-fold in islet homogenates and raised cyclic AMP levels 5-fold in intact islets (both at low and high glucose). Insulin release was enhanced by forskolin only at high glucose. Epinephrine (0.1 microM) inhibited glucose- and forskolin-induced insulin release to basal rates. At the same time epinephrine potentiated forskolin-elevated cyclic AMP levels. In contrast epinephrine attenuated forskolin-stimulated adenylate cyclase activity in islet homogenates. At low glucose, both alpha 2- and beta-adrenergic blockade counteracted the epinephrine potentiation, each by 50%. At high glucose the effect was mainly beta-adrenergic in nature. The actions of epinephrine in the presence of a beta-blocker were mimicked by the alpha 2-agonist clonidine. Despite the variations in cyclic AMP levels stimulated insulin release was always inhibited by activation of alpha 2-receptors. Finally, insulin release stimulated by exogenous cyclic AMP was abolished by epinephrine. These results suggest that epinephrine inhibits insulin release at a step distal to the generation of cyclic AMP.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1980

Lambda receptor in the outer membrane of Escherichia coli as a binding protein for maltodextrins and starch polysaccharides.

The starch polysaccharides amylose and amylopectin are not utilized by Escherichia coli, but are bound by the bacteria. The following evidence supports the view that the outer membrane lambda receptor protein, a component of the maltose/ maltodextrin transport system is responsible for the binding. (i) Amylose and amylopectin both inhibit the transport of maltose into E. coli. (ii) Both polysaccharides prevent binding of non-utilizable maltodextrins by the intact bacterium, a process previously shown to be dependent on components of the maltose transport system (T. Ferenci, Eur. J. Biochem., in press). (iii) A fluorescent amylopectin derivative, O-(fluoresceinyl thiocarbamoyl)-amylopectin, has been synthesized and shown to bind to E. coli in a reversible, saturable manner. Binding of O-(fluoresceinyl thiocarbamoyl)-amylopectin is absent in mutants lacking the lambda receptor, but mutations in any of the other components of the maltose transport system do not affect binding as long as lambda receptor is present. (iv) Using the inhibition of lambda receptor-dependent O-(fluoresceinyl thiocarbamoyl)-amylopectin binding as an assay, the affinities of the lambda receptor for maltodextrins and other sugars have been estimated. The affinity for dextrins increases with increasing degree of polymerization (K(d) for maltose, 14 mM; for maltotetraose, 0.3 mM; for maltodecaose, 0.075 mM). Maltose and some other di- and trisaccharides are inhibitory to amylopectin binding, but only at concentrations above 1 mM.

Amylopectin↗
PubMedDate not supplied

The Ullrich-Hodge Alternative Therapy Assessment Model. Teaching students to evaluate patients for use, motivation, and risks.

Americans are increasingly turning to complementary and alternative medical therapies as a way of maintaining or improving their health. As with other treatment modalities, nurses have a responsibility to implement the nursing process as it relates to the use of alternative therapies. This article introduces a model for identifying patients who use alternative therapies and evaluating their knowledge base, motivation, and degree of risk.

Complementary Therapies↗
PubMedDate not supplied

[Homicides--the sociodemographic background of the offender and the behavioral symptoms].

The authors examined 261 forensic-psychiatric reports to determine whether persons convicted of criminal homicide differed from persons convicted of other crimes with regard to personal biography, sociodemographic milieu, and character traits. Both groups were found to come from similarly disadvantaged social backgrounds. Murderers could not be distinguished on the basis of biographical data alone. The parameters found to be distinctive of murderers were: site of the crime, criminal-victim relationship, motive for the act, intoxication at the time of the crime, and the perpetrator's opinion regarding the purpose and intent of the homicide. The present findings confirm some of the results obtained by other authors on this topic.

Adolescent↗
PubMedDate not supplied

ANCA against the bactericidal/permeability increasing protein (BPI-ANCA) can compromise the antibiotic function of BPI in a Wegener's granulomatosis patient.

A 54-year old Wegener's granulomatosis patient with PR3-ANCA at diagnosis 2 years ago was admitted with a pulmonary relapse and new subglottic stenosis preceded by pulmonary infections. The patient presented with bactericidal/permeability increasing protein (BPI)-ANCA in ELISA whereas at the same time PR3-ANCA had disappeared. Bronchoalveolar lavage revealed pulmonary infection with Gram-negative bacteria. After antibiotic treatment, immunosuppression was started with cyclophosphamide and infliximab due to refractory disease. Remission was induced and BPI-ANCA disappeared. A bacterial growth inhibition assay with BPI and the patient's IgG purified during the actual pulmonary relapse showed inhibition of the antimicrobial activity of BPI in vitro, in contrast to IgG from sera taken 2 years before and after remission was induced. The patient's BPI-ANCA recognised the bioactive N-terminal portion of BPI. Thus a possible mechanism is demonstrated for how BPI-ANCA may contribute to a pro-inflammatory setting during the development of a pulmonary relapse in the absence of PR3-ANCA by impeding bacterial clearance.

Anti-Bacterial Agents↗