bluuebunny/crossref_metadata_2025_split huggingface dataset:
Involvement of reduced sensitivity to Ca2+ in β‐adrenergic action on airway smooth muscle
Authors: Oguma T. , Kume H. , Ito S. , Takeda N. , Honjo H. , Kodama I. , Shimokata K. , Kamiya K. 
Published: January 2006

SummaryBackground
It is well known that β‐adrenoceptor agonists (β‐agonists) cause relaxation in airway smooth muscle mediated by a reduction in the concentration of intracellular Ca2+ ([Ca2+]i). However, little is currently known regarding whether reduced sensitization to Ca2+ is involved in the β‐adrenergic relaxation.Objective
This study was designed to determine the intracellular mechanisms underlying suppression of Ca2+ sensitization in β‐adrenergic relaxation (Ca2+‐independent relaxation by β‐agonists).Methods
Isometric tension and [Ca2+]i were simultaneously measured in fura‐2‐loaded strips isolated from guinea‐pig tracheal smooth muscles. The relationships between tension and [Ca2+]i were examined in the inhibitory action of isoprenaline (ISO) and other cAMP‐related agents against methacholine‐induced contraction.Results
The concentration‐inhibition curve for ISO against methacholine in tension was significantly dissociated from the curve for ISO in [Ca2+]i. In ISO‐induced relaxation, a reduction in tension was significantly greater than that in [Ca2+]i. This phenomenon was mimicked by other cAMP‐related agents: forskolin and dibutyryl‐cAMP. In contrast, the inhibitory action of SKF‐96365, a non‐selective inhibitor of Ca2+ channels, was associated with that in [Ca2+]i. In the presence of Rp‐cAMPS, an inhibitor of protein kinase A (PKA), ISO caused an equivalent relaxation with less reduction in [Ca2+]i. The effects of ISO were not affected by Y‐27632, an inhibitor of Rho‐kinase, or by bisindolylmaleimide, an inhibitor of protein kinase C. ISO failed to inhibit contraction elicited by calyculin A, an inhibitor of myosin phosphatase.Conclusion
β‐Adrenergic action antagonizes not only Ca2+ mobilization but also Ca2+ sensitization in methacholine‐induced contraction. The cAMP/PKA‐independent, Gs‐direct action is more potent in Ca2+‐independent relaxation by β‐agonists than the cAMP/PKA‐dependent pathway. Moreover, myosin phosphatase is a fundamentally affected protein in the reduced response to Ca2+ mediated by β‐agonist. Our results may provide evidence that this Ca2+ desensitization is a novel target for a reliever medication using rapid‐acting β‐agonists in acute asthma management.
Sequence variants of the secreted phosphoprotein 1 gene are associated with total serum immunoglobulin E levels in a Japanese population
Authors: Tanino Y. , Hizawa N. , Konno S. , Fukui Y. , Takahashi D. , Maeda Y. , Huang S. K. , Nishimura M. 
Published: January 2006

SummaryBackground
Secreted phosphoprotein 1 (SPP1) is a cytokine with pleiotrophic immunological activities, including activation of macrophage chemotaxis and T‐helper type 1 (Th1) immune responses. SPP1 gene polymorphisms have been shown to be associated with several immune inflammatory diseases including multiple sclerosis (MS), which is characterized by fewer allergic symptoms and lower numbers of allergen sensitizations.Objective
The present study examined whether SPP1 gene polymorphisms are associated with total serum IgE levels, atopy and asthma in a Japanese population.Methods
This case–control association analysis examined 611 subjects, including 268 subjects with asthma. We genotyped three promoter and two exon polymorphisms at SPP1: −1687A/G; −381T/C; −94 deletion/G; 5891C/T; and 7052T/C.Results
Association analyses of SPP1 polymorphisms showed that homozygosities for the 5891T allele (P=0.009) and 7052C allele (P=0.001) were significantly associated with increased levels of total IgE in non‐asthmatic subjects. However, these variants were not associated with asthma and atopy. Interestingly, individuals carrying the 5891C allele, which is more prevalent in patients with MS in Japanese populations, displayed significantly lower levels of total serum IgE. Individuals homozygous for the 7052C allele, which is associated with development of systemic lupus erythematosus, displayed significantly higher total serum IgE levels.Conclusion
These findings suggest that genetic polymorphisms in SPP1 may play a role in controlling basal levels of total serum IgE, independent of atopy.
Allergen‐induced interleukin‐9 production in vitro: correlation with atopy in human adults and comparison with interleukin‐5 and interleukin‐13
Authors: Devos S. , Cormont F. , Vrtala S. , Hooghe‐Peters E. , Pirson F. , Van Snick J. 
Published: January 2006

SummaryBackground
The contribution of IL‐9 to human atopy is supported by genetic studies. However, IL‐9 production in response to allergen in vitro has been reported only in children.Objective
Study IL‐9 induction by allergen in adults, compare it with IL‐5 and IL‐13 and evaluate its association with atopy.Methods
Peripheral blood mononuclear cell (PBMC) from control adults and from atopic patients were cultured with various allergens or phytohaemagglutinin (PHA) and secreted IL‐5, IL‐9 and IL‐13 were measured by ELISA.Results
IL‐9 was produced in response to Dermatophagoides pteronyssinus (Der p) by PBMC from Der p‐hypersensitive adults at levels equivalent to those induced by PHA but with slower kinetics. The induction of IL‐9 was allergen specific, reflecting donor RAST profile. In Der p‐triggered reactions of non‐atopic and atopic subjects, IL‐9 showed the highest selectivity for atopics, IL‐5 and IL‐13 being produced more frequently in non‐atopic donors. Significant correlations with specific IgE titres were found for IL‐9 with all allergens tested (Der p and two peptides of Bet v 1 birch allergen). For IL‐5 and IL‐13, they were in the same range for Der p but more variable for birch allergens. Patterns of cytokine production by individual patients in response to allergen reflected these differences: for Der p, IL‐5, IL‐9 and IL‐13 productions were strongly correlated but for birch IL‐5 differed from the latter two. The in vitro production of IL‐9 reflected clinical hypersensitivity profiles and was higher in individuals with asthma than in those with disease limited to rhinitis and/or conjunctivitis.Conclusions
Allergen‐triggered IL‐9 production in vitro is an excellent marker for atopy in adults given its virtual absence in allergen‐stimulated PBMC from non‐atopic individuals and its correlation with allergen‐specific IgE and asthma.
The diagnosis of Brazil nut allergy using history, skin prick tests, serum‐specific immunoglobulin E and food challenges
Authors: Ridout S. , Matthews S. , Gant C. , Twiselton R. , Dean T. , Arshad S. H. 
Published: January 2006

SummaryBackground
Allergy to Brazil nut is a relatively common nut allergy and can be fatal. However, the evidence is lacking regarding the best approach to its diagnosis.Objective
We sought to determine the relative merits of history, skin prick testing, measurement of serum‐specific IgE and challenge in the diagnosis of Brazil nut allergy.Methods
Fifty‐six children and adults with a history of an allergic reaction to Brazil nut or evidence of sensitization were investigated by questionnaire (n=56), skin prick tests (SPTs) (n=53), measurement of serum‐specific IgE to Brazil nut (n=54) and double‐blind, placebo‐controlled labial, and if necessary oral, challenges (n=19).Results
Brazil nut allergy occurred in highly atopic individuals of any age with a strong family history of atopy. In 24 of 56 (43%), the history of an immediate reaction was sufficient to make a diagnosis with confidence and an oral challenge was considered unsafe. Of the 19 subjects undertaking the ‘gold standard’ test of a double‐blind, placebo‐controlled, food challenge, all six subjects with a SPT of at least 6 mm had a positive challenge and all three subjects with a SPT of 0 mm had a negative challenge. In the remaining 10 (53%) subjects, where SPT was between 1 and 5 mm and serum‐specific IgE was less than 3.5 kU/L, an oral challenge was performed resulting in three positive and seven negative challenges.Conclusion
A combination of history, SPT and serum‐specific IgE was adequate in achieving a diagnosis in the majority (77%) patients with suspected Brazil nut allergy. However, a doubtful history with SPT between 1 and 5 mm, or a serum‐specific IgE less than 3.5 kU/L may require an oral challenge to help determine the risk of a Brazil nut allergic reaction.
Heart specific up‐regulation of genes for B‐type and C‐type natriuretic peptide receptors in diabetic mice
Authors: Christoffersen C. , Bartels E. D. , Nielsen L. B. 
Published: January 2006

AbstractBackground  Diabetes may cause cardiomyopathy characterized by cardiac fibrosis. Recent studies of genetically modified mice have elucidated a role of the natriuretic peptides (NP), type‐A and type‐B (ANP and BNP), and their common receptor [natriuretic peptide receptor (NPR), type‐A] in development of cardiac fibrosis. The role of NP type‐C (CNP) and NPR type‐B (NPR‐B) in the heart is less well established. In this study we examined if diabetes alters heart expression of the genes encoding the NP and its receptors.Materials and methods  Cardiac mRNA was quantified by real‐time PCR in diabetic streptozotocin (STZ)‐treated and ob/ob‐mice and nondiabetic control mice.Results  The ob/ob‐mice with type‐II diabetes displayed highly significant increases of the cardiac mRNA expression of NPR‐B and NPR‐C while the expression levels of NPR‐A, ANP, BNP, and CNP mRNA were similar in ob/ob‐mice and controls. Mice with STZ‐induced type‐I diabetes also showed an increase of heart NPR‐B mRNA expression at 12 weeks, but not at 3, 6 or 9 weeks after STZ‐treatment. The ANP and NPR‐C mRNA expressions were only altered after 3 weeks, whereas BNP, CNP and NPR‐A mRNA expressions were not altered in STZ‐treated‐mouse hearts at any of the time points.Conclusions  The results show that diabetes in mice confers increased NPR‐B gene expression in the heart, suggesting that increased NPR‐B signalling may affect development of diabetic cardiomyopathy.
Green tea polyphenol (–)‐epigallocatechin‐3‐gallate inhibits ethanol‐induced activation of pancreatic stellate cells
Authors: Asaumi H. , Watanabe S. , Taguchi M. , Tashiro M. , Nagashio Y. , Nomiyama Y. , Nakamura H. , Otsuki M. 
Published: January 2006

AbstractBackground  Activated pancreatic stellate cells (PSCs) play a central role in the pathogenesis of pancreatic fibrogenesis and inflammation. Ethanol, a major cause of chronic pancreatitis, directly induces PSC activation and oxidative stress. Inhibition of PSC activation or stimulation to PSC might be an effective therapeutic strategy for the prevention of pancreatic fibrosis, and (–)‐epigallocatechin‐3‐gallate (EGCG), a major component of green tea extracts, is a potent antioxidant of polyphenols. Therefore, we examined the mechanisms through which ethanol induces oxidative stress on PSCs and evaluated the effect of EGCG on activation and cell functions of ethanol‐stimulated PSCs.Materials and methods  The PSCs were isolated from the pancreas of male Wister rats with Nycodenz gradient methods and cells between passages one and four were used. Isolated PSCs were cultured with ethanol (50 mM) in the absence or presence of EGCG (5 µM or 25 µM).Results  The EGCG pre‐treatment abolished ethanol‐induced lipid peroxidation of the cell membrane, loss of total superoxide dismutase (SOD) activity and suppressed ethanol‐induced gene expressions of Mn‐ and Cu/Zn‐SOD. EGCG also suppressed ethanol‐induced p38 mitogen‐activated protein (MAP) kinase phosphorylation, α‐smooth muscle actin production in PSCs and activated transforming growth factor‐β1 secretion into the medium. Furthermore, EGCG inhibited ethanol‐induced type‐I procollagen production and collagen secretion. In addition, EGCG inhibited transformation of freshly isolated cells to activated myofibroblast‐like phenotype.Conclusions  Our results suggest that green tea and polyphenols could prevent pancreatic fibrosis by inhibiting PSC activation through the antioxidative effect.
Hypoxic inhibition of human myometrial contractions in vitro: implications for the regulation of parturition
Authors: Bugg G. J. , Riley M. J. , Johnston T. A. , Baker P. N. , Taggart M. J. 
Published: January 2006

AbstractBackground  Insufficient tissue oxygenation is a likely contribution to weak, inco‐ordinate human uterine contractile activity characteristic of prolonged, dysfunctional labour. However, the direct effects of hypoxia on human myometrial contractility has, surprisingly, not yet been detailed. Therefore, we report the influence of hypoxia on spontaneous and agonist‐induced carbachol, prostaglandin (PGF2α), and oxytocin contractions of myometria from nonpregnant and pregnant women.Materials and methods  Uterine biopsies were obtained from pregnant women at term undergoing elective Caesarean section and nonpregnant women undergoing hysterectomy. Myometrial strips were equilibrated at 37 °C in normoxic physiological salt solution (95% air/5% CO2) and the influence of hypoxia (95% N2/5% CO2) on contractility was investigated.Results  Hypoxia resulted in a significant reduction in spontaneous contractile function; nonpregnant tissue was less resistant to the deleterious effects of hypoxia. Agonist‐induced contractions, while being more resistant to hypoxia than spontaneous contractions, were also significantly inhibited. In myometria of pregnant women the PGF2α‐ or oxytocin‐induced contractility was more resistant to hypoxia than carbachol. Finally, the inhibitory actions of hypoxia were exacerbated with repeated oxytocin administration with a more severe effect on contractile integral than on initial phasic contraction amplitude.Conclusions  We detail, for the first time, the effects of hypoxia on contractility of human myometria from nonpregnant and pregnant women. Physiologically important uterotonic agents are more resistant to the effects of hypoxia than spontaneous contractions although repeated stimulation with oxytocin during hypoxia results in progressively less force. The results indicate that if significant hypoxia occurs in vivo then it is a likely contributory factor to the pathways underlying prolonged dysfunctional labour.
Influence of a subsequent meal on the oro‐cecal transit time of a solid test meal
Authors: Priebe M. G. , Wachters‐Hagedoorn R. E. , Landman K. , Heimweg J. , Elzinga H. , Vonk R. J. 
Published: January 2006

AbstractBackground  Oro‐cecal transit time (OCTT) is determined for clinical diagnostics of intestinal complaints and research purposes. Ingestion of a subsequent meal during the test period shortens the OCTT of a liquid test meal (glucose solution), as previously reported. This study was conducted to determine whether the same phenomenon occurs after ingestion of a solid test meal.Materials and methods  The OCTT of a pancake was measured with the lactose‐[13C]‐ureide breath test on two occasions in 28 volunteers. All the volunteers took the same subsequent meal once at 4 h and at 6 h after ingestion of the pancake.Results  In 16 of the 56 tests no increase in breath‐13CO2 was observed. No statistically significant difference was found between the OCTTs of the test meal after ingestion of the subsequent meal at 4 h or 6 h (367; 311–405 min and 290; 370–405 min, median quartiles, respectively) (P = 0·14, n = 18). Only a subgroup (n = 4) with a short OCTT in the test with the 4‐h subsequent meal (278; 259–296 min) tended to have a longer OCTT in the test with the 6‐h subsequent meal (390; 379–401 min; P = 0·059).Conclusion  The effect of the ingestion of a subsequent meal on the transit time of a test meal is shown to be dependent on the physical form and/or caloric content of the test meal.
Effects of antibodies obtained from patients with dilated cardiomyopathy on the function of isolated rat hearts
Authors: Staudt Y. , Trimpert C. , Birkenmeier K. , Krieg T. , Bemmann T. , Beug D. , Felix S. B. , Staudt A. 
Published: January 2006

AbstractBackground  Cardiac autoantibodies may play a pathophysiological role in cardiac dysfunction of patients suffering from dilated cardiomyopathy (DCM). Immunoadsorption (IA), which removes antibodies from patients’ plasma, may consequently improve cardiac function in DCM. The functional effects of DCM antibodies are only partly understood.Materials and methods  DCM patients (n = 10) were treated with IA by application of antibody columns directed against human immunoglobulin (Ig). IA was also performed with plasma taken from 10 healthy donors (controls). The antibodies eliminated and purified by IA were collected and dialysed. Rat hearts were isolated and perfused retrogradely via the aorta in Langendorff mode. During constant‐pressure and constant‐volume perfusion of the hearts, the influence of diluted antibodies on contractility, relaxation, and on coronary perfusion was analysed.Results  Antibodies obtained from controls had no effect on contractility and relaxation of isolated perfused hearts during constant‐pressure and constant‐volume perfusion. In contrast, during constant‐pressure perfusion, collected DCM antibodies caused immediate and dose‐related reduction of contractility (dLVP/dtmax: dilution −1 : 32 = −7·1 ± 1·1%; dilution −1 : 2 = −20·1 ± 2·1%; P < 0·001) and diastolic relaxation (dLVP/dtmin: dilution −1 : 32 = −11·1 ± 1·5%; dilution −1 : 2 = −23·9 ± 2·2%; P < 0·001). The heart rate did not change significantly in either group. The effects of DCM antibodies on contractility and relaxation remained detectable during constant‐volume perfusion. The observed reduction of contractility and diastolic relaxation was accompanied by impairment of coronary perfusion.Conclusion  In the rat heart, antibodies obtained from DCM patients may impair contractility and relaxation, and thereby probably also coronary perfusion.
Lipoprotein(a), type 2 diabetes and vascular risk in coronary patients
Authors: Saely C. H. , Koch L. , Schmid F. , Marte T. , Aczel S. , Langer P. , Hoefle G. , Drexel H. 
Published: January 2006

AbstractBackground  Lipoprotein(a) [Lp(a)] is an important cardiovascular risk factor in the general population. However, prospective data on the vascular risk conferred by Lp(a) in patients with diabetes mellitus are scarce and controversial. It is not known whether the diabetic state affects the association of Lp(a) with vascular events among coronary patients.Design  We measured Lp(a) in 587 consecutive patients undergoing coronary angiography for the evaluation of coronary artery disease. The incidence of vascular events was recorded over 4 years.Results  At baseline, Lp(a) was significantly lower in patients with type 2 diabetes (T2DM) (n = 136) than in nondiabetic individuals (11 (0·8–30) mg dL−1 vs. 16 (0·8–51) mg dL−1; P = 0·025). Prospectively, Lp(a) was a strong and independent predictor of vascular events in nondiabetic patients (standardized adjusted hazard ratio (HR) = 1·461 (1·121–1·904); P = 0·005), but not in patients with T2DM [HR = 0·812 (0·539–1·223); P = 0·320]. An interaction term diabetes × Lp(a) was significant (P = 0·008), indicating that Lp(a) was a significantly stronger predictor of vascular events in nondiabetic patients than in patients with T2DM.Conclusions  Lp(a) in diabetic coronary patients is low and not associated with the incidence of vascular events. Although measurement of Lp(a) provides useful information in nondiabetic coronary patients, it is of little value in coronary patients with T2DM.
Structural relationship of curcumin derivatives binding to the BRCT domain of human DNA polymerase λ
Authors: Takeuchi Toshifumi , Ishidoh Tomomi , Iijima Hiroshi , Kuriyama Isoko , Shimazaki Noriko , Koiwai Osamu , Kuramochi Kouji , Kobayashi Susumu , Sugawara Fumio , Sakaguchi Kengo , Yoshida Hiromi , Mizushina Yoshiyuki 
Published: January 2006

We previously reported that phenolic compounds, petasiphenol and curcumin (diferuloylmethane), were a selective inhibitor of DNA polymerase λ (pol λ) in vitro. The purpose of this study was to investigate the molecular structural relationship of curcumin and 13 chemically synthesized derivatives of curcumin. The inhibitory effect on pol λ (full‐length, i.e. intact pol λ including the BRCA1 C‐ terminal [BRCT] domain) by some derivatives was stronger than that by curcumin, and monoacetylcurcumin (compound 13) was the strongest pol λ inhibitor of all the compounds tested, achieving 50% inhibition at a concentration of 3.9 µm. The compound did not influence the activities of replicative pols such as α, δ, and ɛ. It had no effect on pol β activity either, although the three‐dimensional structure of pol β is thought to be highly similar to that of pol λ. Compound 13 did not inhibit the activity of the C‐terminal catalytic domain of pol λ including the pol β‐like core, in which the BRCT motif was deleted from its N‐terminal region. MALDI‐TOF MS analysis demonstrated that compound 13 bound selectively to the N‐terminal domain of pol λ, but did not bind to the C‐terminal region. Based on these results, the pol λ‐inhibitory mechanism of compound 13 is discussed.
Epstein–Barr virus infection negatively impacts the CXCR4‐dependent migration of tonsillar B cells
Authors: Ehlin‐Henriksson Barbro , Mowafi Frida , Klein George , Nilsson Anna 
Published: January 2006

SummaryThe primary Epstein–Barr virus (EBV) infection occurs in the oropharynx, where the virus infects B cells and subsequently establishes latency in the memory B‐cell compartment. EBV has previously been shown to induce changes in the cell surface expression of several chemokine receptors in cell lines and the transfection of EBNA2 or LMP1 into a B‐cell‐lymphoma‐derived cell line decreased the expression of CXCR4. We show that in vitro EBV infection reduces the expression of CXCR4 on primary tonsil B cells already 43 hr after infection. Furthermore, EBV infection affects the chemotactic response to stromal cell‐derived factor (SDF‐1)α/CXCL12, the ligand for CXCR4, with a reduction of SDF‐1α‐induced migration. To clarify whether this reduced migration is EBV‐specific or a consequence of cell activation, tonsillar B cells were either infected with EBV, activated with anti‐CD40 and interleukin‐4 (IL‐4) or kept in medium. Activation by anti‐CD40 and IL‐4 decreased the CXCR4 expression but the CD40 + IL‐4‐stimulated cells showed no reduction of chemotactic efficacy. Our finding suggests that changing the SDF‐1α response of the EBV‐infected B cells may serve the viral strategy by directing the infected cells into the extrafollicular areas, rather than retaining them in the lymphoepithelium.
Blockade of OX40‐ligand after initial triggering of the T helper 2 response inhibits mercuric chloride‐induced autoimmunity
Authors: MacPhee Iain A. M. , Yagita Hideo , Oliveira David B. G. 
Published: January 2006

SummaryMercuric chloride (HgCl2)‐induced autoimmunity in Brown Norway rats is a spontaneously resolving autoimmune response driven by the activation of T helper type 2 lymphocytes (Th2 cells). Treatment with antibody to OX40‐ligand (OX40‐L) from the time of the first HgCl2 injection for 12 days had little effect. Delayed treatment commenced 8 days after the first HgCl2 injection significantly suppressed immunoglobulin E production, splenomegaly, weight loss and mortality. This makes OX40/OX40‐L signalling an attractive therapeutic target for Th2‐driven autoimmune diseases. Intravenous administration of the murine antibody to OX‐40‐L elicited a vigorous anti‐mouse immunoglobulin antibody response that was significantly enhanced compared to the response to control immunoglobulin. It is likely that this response significantly reduced the plasma half‐life of the anti‐OX40‐L antibody and this observation has clear implications for the interpretation of data from experiments where anti‐OX40‐L is used in vivo.