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  • 1
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Several observations suggest that cyclic GMP might regulate some aspect of neuromuscular physiology or metabolism in the lobster, Homarus americanus: (1) lobster muscle is one of the richest known sources of cyclic GMP-dependent protein kinase, (2) the preparation contains several phosphoproteins whose state of phosphorylation is affected by cyclic GMP more effectively than by cyclic AMP, and (3) guanylate cyclase and phosphodiesterase are active in this tissue. However, no factor has yet been identified that alters lobster muscle cyclic GMP levels. We have screened extracts of neural and neurosecretory structures for the capacity to promote cyclic GMP accumulation in isolated exoskeletal muscles. Extracts of the sinus gland (a neurohemal organ found in the eyestalk) contain a factor that induces up to 100-fold increases in muscle cyclic GMP content, whereas extracts of other tissues are ineffective. This factor can also act on targets other than muscle, with hepatopancreas, testis, and neuronal tissue showing the largest responses. The sinus gland factor does not appear to affect cyclic GMP metabolism by depolarizing the preparation or by mobilizing extracellular Ca2+. The effect on cyclic GMP levels is dose-dependent and linear with time. Biological activity is destroyed by boiling and by 90% ethanol. It is also destroyed by trypsin, chymotrypsin, or pronase, which suggests that the factor is a protein or peptide. Both gel filtration chromatography and experiments using dialysis tubing with different molecular weight exclusion limits indicate that the factor has an apparent molecular weight of 5,000–12,000 daltons. A preliminary fractionation scheme, based on gel filtration, ion-exchange, and reverse-phase chromatography, gives 〉1,300-fold purification. Our long-range goal is to purify this factor to homogeneity, compare it to other peptide hormones, and use it as a probe to evaluate the role of cyclic GMP at the neuromuscular junction.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Clinical & experimental allergy 27 (1997), S. 0 
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background Nitric oxide (NO) plays a major role in the regulation of vascular tone and in non-specific host defence. The epithelium in the paranasal sinuses was recently identified as the major site of NO production in the upper airways.Objective To investigate NO status in allergic rhinitis, we compared the NO concentration in the nasal cavities of control subjects (n= 19) and in patients with allergic rhinitis (n= 36) with symptoms (WS, n= 17) or without symptoms (WOS, n= 19) on the day of the test.Methods NO concentration was measured using a chemiluminescent analyser aspiring from each nasal cavity at a sampling flow rate of 0.7L/min, before and 10min after administration of a nasal vasoconstrictor.Results The mean NO concentration (± se) in the control was 235 ± 11 ppb and 225 ± 9 ppb in the right and left nostrils respectively, and was decreased by 14% and 12% by the nasal vasoconstrictor (P 〈 0.001). The NO concentration in patients with allergic rhinitis was significantly higher in the right and left nostrils (382 × 20 ppb and 396 ± 28 respectively, P 〈 0.0001 versus control). All WOS patients demonstrated normal or increased NO concentrations in both nostrils, whereas two WS patients showed decreased NO concentrations in the left nostril. Inhalation of a nasal vasoconstrictor increased NO concentration by 6% and 27% in the right and left nostrils respectively in WS patients.Conclusion Nasal NO concentration is increased in patients with allergic rhinitis. Interestingly, patients without symptoms on the day of the test also showed a clear-cut increase in nasal NO production, which could reflect a permanent inflammation of the sinus mucosa.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Twenty-one patients, who had previously experienced an anaphylactic reaction to suxamethonium during general anaesthesia, were selected for this study. Initially, skin tests with muscle relaxants were carried out in the twenty-one patients, detection of specific anti-choline IgE in nineteen, and leucocyte histamine release in seventeen. These three tests were then repeated between 1 year and 4 years after the initial evaluation. In the majority of patients, sensitization to the muscle relaxants persisted for more than 1 year after the anaphylactic reaction. Only three patients out of twenty-one (4%) had negative skin tests when retested 1–4 years later. A reduction in leucocyte histamine release was noticed in one of the seventeen retested patients (6%). Modifications of anti-choline IgE were observed in five of nineteen patients (26%). The persistence of sensitization to suxamethonium may result from repeated stimulation by occasional contacts with quaternary ammonium compounds. This study demonstrates the reliability of skin tests, leucocyte histamine release and detection of anti-choline IgE to diagnose allergic reactions to suxamethonium, even when they are performed a long time after the initial anaphylactic reaction.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1398-9995
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background:  High concentrations of nitric oxide (NO) originating from a type-2 nitric oxide synthase (NOS2) located within the paranasal sinuses are measured in nasal air in man. NO is believed to play a central role in nonspecific defense of paranasal sinuses. Glucocorticoids (GCs), a therapeutic often used for a wide range of diseases, is known to strongly downregulate NOS2.Aims of the study:  To investigate the effect of very high intravenous doses of GCs on nasal NO in man.Methods:  Nasal NO was measured in 15 patients without any history of allergy or chronic airway disorder who were treated for 3 days with a daily dose of 1000 mg methylprednisolone for an exacerbation of multiple sclerosis. Nasal NO was also measured in 30 matched control subjects.Results:  In control subjects, the maximal value of nasal NO [mean (SE)] was 233 (8) part per billion (ppb), and did not differ from patients with multiple sclerosis [maximum value: 219 (13) ppb; left nostril: 214 (12) ppb; right nostril: 215 (12) ppb]. After GCs treatment, nasal NO increased in patients [maximum value: 250 (13) ppb (P 〈 0.0001); left nostril: 249 (12) ppb (P 〈 0.0001); right nostril: 244 (13) ppb (P 〈 0.0001)].Conclusions:  We conclude that GCs do not decrease but even increase nasal NO.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1398-9995
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background: No validated assessment of allergic rhinitis (AR) is presently available that can be used in population studies in the absence of medical diagnosis and of objective measurements of allergy. To compensate for this lack, a quantitative Score For Allergic Rhinitis (SFAR) ranging between 0 and 16 has been developed by experts. Methods: The SFAR, encompassing eight features of AR, was validated in three different ways: 1) among 269 outpatients taking the specialist's diagnosis of AR and skin prick tests (SPT) positivity as a gold standard (diagnosis validation); 2) using psychometric methods (internal validation); and 3) in a random population-based sample of 3001 individuals by telephone interview (population acceptability). Results: A SFAR value ≥ 7 allowed satisfactory discrimination between the outpatients with AR from those without (sensitivity = 74% [95% confidence interval CI: 0.69,0.79], specificity = 83% [0.79, 0.87], positive predictive value = 84% [0.80, 0.88], negative predictive value = 74% [0.69, 0.79] and Youden's index = 0.57, respectively). Internal consistency of the score was also high (among others, Cronbach's alpha coefficient = 0.79). On average, it took only 3 min for the individuals interviewed on the phone to complete the questionnaire, the questions of which were well understood. Among these subjects, the prevalence of AR was 21% [95% CI: 19.5%, 22.5%], which is comparable to other determinations in France. Conclusions: The newly a priori proposed Score For Allergic Rhinitis (SFAR) is easy to use and can be useful to estimate prevalence and to study causation of AR in population settings.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1398-9995
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Fluticasone propionate aqueous spray, a new intranasal corticosteroid preparation, and disodium eromoglyeate 2% aqueous nasal spray, an established preventive treatment for seasonal allergic rhinitis, were compared in a double-blind, double-dummy, parallel-group, multicentric study in France. A total of 218 patients with seasonal allergic rhinitis caused by grass pollen (verified by positive skin prick test) were preventively treated before the onset of the grass pollen season with either fluticasone propionate 200 μg once daily or disodium cromoglycate 5.2 mg four times daily. Half of these doses was given in each nostril. Treatment started before the onset of the pollen season in most patients (178/218). Diary cards, including symptoms of rhinitis and usage of nasal sprays, were filled in twice daily for 5 weeks.Terfenadine in 60-mg tablets and eye-drops could be used as rescue medications. We treated 110 patients with fluticasone propionate and 108 patients with disodium cromoglycate. Patients treated with flutieasone propionate had significantly more days free of primary efficacy symptoms of sneezing (P 〈 0.001) and nasal discharge during the day (P= 0.002), as well as free of all the other nasal symptoms (P 〈 0.0l), and significantly lower median scores (P 〈 0.05) for all nasal symptoms except nasal discharge than patients treated with disodium cromoglycate. There was no difference in eye symptoms or in rescue medication use between the two groups. Compliance with the treatment was assessed. Eleven patients recorded incorrect use of both nasal sprays for over 25% of days, and 55 patients recorded incorrect use of four-times-daily spray only; no patient recorded incorrect use of morning spray only. Both treatments were generally well tolerated.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1398-9995
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background:  To improve asthma control, the management of rhinosinusitis often leads the physician to perform sinonasal imaging and/or nasal endoscopy, but their respective contributions are still insufficiently understood.Objective:  To evaluate the potential contribution of a symptoms questionnaire, sinus radiography (SR) and computed tomography (CT) scan to the diagnosis of nasal diseases in asthmatic patients when compared with ENT examination.Methods:  A total of 124 patients completed a questionnaire on nasal symptoms administered by the chest physician. Then, they underwent ENT examination. On the same day, SR and CT scans were performed independently.Results:  Patients (80.3%) had nasal symptoms during the month preceding the consultation. The ENT examination was normal in 8.1% (n = 10) and revealed rhinitis in 57.3% (n = 71), rhinosinusitis in 14.5% (n = 18) and nasal polyposis in 20.2% (n = 25). For rhinitis, the negative predictive value of bilateral nasal obstruction was 87.8%. Both SR and CT had low sensitivity and specificity. For rhinosinusitis, the negative predictive value of nasal symptoms varied from 85.4 to 95.2%. Sinus CT was at least as accurate as SR for the diagnosis of rhinosinusitis. In a multivariate analysis, only the CT scan (score ≥12) appeared to be significantly associated with the diagnosis of nasal polyposis.Conclusion:  In asthmatic patients, physicians need to enquire systematically about the existence of nasal symptoms by using this simple questionnaire which is sensitive for rhinitis, and has good negative predictive value for excluding rhinosinusitis and nasal polyposis.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Allergy 50 (1995), S. 0 
    ISSN: 1398-9995
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The tachykinin substance P (SP) is present in lung sensory nerve endings and may be released after neurogenic stimulation. Its role in the pathogenesis of asthma is still unclear. Nevertheless, it may play a major role in airway neurogenic inflammation. Alveolar macrophages are the predominant cells of the airway space and are involved in various types of airway inflammation. We studied guinea pig alveolar macrophage response to SP and other related peptide (C- and N-terminal sequences, NK1-receptor agonist) stimulation. Alveolar guinea pig macrophages were recovered by bronchoalveolar lavage (BAL). Macrophage reactive oxygen intermediate (ROI) production was studied by luminol-dependent chemiluminescence with several concentrations of SP and related peptides. Eicosanoid synthesis after stimulation was evaluated by thin-layer chromatography (TLC) and enzyme-linked immunosorbent assay (ELISA). SP, C-terminal sequence, and NKl-receptor agonist significantly increased ROI production by alveolar macrophages (P〈0.01). NK1 -agonist and C-terminal sequence modified arachidonic acid metabolism and induced a significant increase in prostaglandin (PG)D2 synthesis (211% and 66%, respectively). We concluded that SP and related peptides directly affect guinea pig alveolar macrophages by inducing the production of inflammatory metabolites.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1365-2958
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: Staphylococcal γ-haemolysins are bicomponent toxins in a family including other leucocidins and α-toxin. Two active toxins are formed combining HlgA or HlgC with HlgB. Both open pores in lipid membranes with conductance, current voltage characteristics and stability similar to α-toxin, but different selectivity (cation instead of anion). Structural analogies between γ-haemolysins and α-toxin indicate the presence, at the pore entry, of a conserved region containing four positive charges in α-toxin, but either positive or negative in γ-haemolysins. Four mutants were produced (HlgA D44K, HlgB D47K, HlgB D49K and HlgB D47K/D49K) converting those negative charges to positive in HlgA and HlgB. When all charges were positive, the pores had the same selectivity and conductance as α-toxin, suggesting that the cluster may form an entrance electrostatic filter. As mutated HlgC-HlgB pores were less affected, additional charges in the lumen of the pore were changed (HlgB E107Q, HlgB D121N, HlgB T136D and HlgA K108T). Removing a negative charge from the lumen made the selectivity of both HlgA-HlgB D121N and HlgC-HlgB D121N more anionic. Residue D121 of HlgB is compensated by a positive residue (HlgA K108) in the HlgA-HlgB pore, but isolated in the more cation-selective HlgC-HlgB pore. Interestingly, the pore formed by HlgA K108T-HlgB, in which the positive charge of HlgA was removed, was as cation selective as HlgC-HlgB. Meanwhile, the pore formed by HlgA K108T-HlgB D121N, in which the two charge changes compensated, retrieved the properties of wild-type HlgA-HlgB. We conclude that the conductance and selectivity of the γ-haemolysin pores depend substantially on the presence and location of charged residues in the channel.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1432-1424
    Keywords: trout ; intestine ; brush-border membrane ; vesicle ; Cl− conductance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Summary Experiments were performed to determine the presence of a Cl−−OH− exchange (Cl−−H+ cotransport) in the brush-border membranes isolated from the intestinal epithelium of freshwater trout. Determinations of alkaline phosphatase activities have shown that vesicle suspensions had an enrichment factor of about 17 in this enzyme indicating a high degree of purification of the brush-border membrane preparation. Cl− uptake by vesicles in the presence of a proton gradient occurs against a concentration gradient with an overshoot ratio of about 2 and is inhibited by SITS. Several lines of evidence suggest that the mechanism involved is electrical in nature: (i) Cl− uptake is increased when the proton gradient is increased, but there is a linear relationship between the Cl− uptake and the Nernst potential of protons. (ii) Cl− uptake is increased when a proton ionophore is added at low concentration and inhibited at high concentration, suggesting that a proton conductance is involved in the Cl− uptake. (iii) there is a linear relationship between the initial speed of the uptake of increasing Cl− concentrations and the Cl− concentration. (iv) Cl− uptake can be modulated by different potassium gradients with or without valinomycin. It is concluded that the enterocyte of the freshwater trout is not equipped with a Cl−−OH− exchange and the Cl− uptake by vesicles is realized by a Cl− conductance.
    Type of Medium: Electronic Resource
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