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141.
Professor Tim W. Higenbottam John Britton David Lawrence Charles K. Connolly N. Kim Harrison Helen M. Eastham 《BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy》2000,14(4):247-254
Background: Short courses of oral prednisolone are used as rescue therapy for severe asthma exacerbations. This study compares nebulised budesonide or oral prednisolone, both followed by budesonide Turbohaler®, as a treatment for severe asthma exacerbations, in the absence of life-threatening features. Patients and Methods: Thirteen adults admitted to hospital were randomised to receive either nebulised budesonide (4mg 8-hourly) for 48 to 72 hours followed by budesonide Turbohaler® (1600μg twice daily for 7 days, then 800μg twice daily for 21 days) for 28 days or prednisolone (40mg daily) for 9 to 11 days followed by budesonide Turbohaler® (800μg twice daily) for 21 days. The primary efficacy variable was the change from baseline at 48 hours in forced expiratory volume in 1 second (FEV1). Secondary efficacy variables included an assessment of symptom severity (0 = none, 1 = mild, 2 = moderate, 3 = severe). Results: Difficulties were experienced with patient recruitment in the emergency setting. The results presented are from an incomplete study. Change in FEV1 from baseline to 48 hours was not statistically significantly different between the groups (the study was underpowered to detect a difference in change in FEV1, as the power to detect a prespecified difference between groups was 18%). Nebulised budesonide significantly reduced the severity of wheeze after 24 hours compared with prednisolone [estimate of treatment effect = ?0.95; 95% confidence intervals (CI) = ?1.76 to ?0.15; p = 0.0336 between groups] and 48 hours (estimate of treatment effect = ?0.79; 95% CI = ?1.42 to ?0.15; p = 0.0326 between groups). Conclusion: While oral prednisolone or intravenous hydrocortisone, oxygen and bronchodilators are the mainstay of acute management in severe asthma, the results of this study suggest that nebulised budesonide may assist in regaining control of symptoms during exacerbations of asthma. 相似文献
142.
Autocrine motility factor (AMF) is one of the motility cytokines regulating tumor cell migration, therefore identification
of the signaling pathway coupled with it has critical importance. Previous studies revealed several elements of this pathway
predominated by lipoxygenase-PKC activations but the role for tyrosine kinases remained questionable. Motility cytokines frequently
have mitogenic effect as well, producing activation of overlapping signaling pathways therefore we have used B16a melanoma
cells as models where AMF has exclusive motility effect. Our studies revealed that in B16a cells AMF initiated rapid (1–5
min) activation of the protein tyrosine kinase (PTK) cascade inducing phosphorylation of 179, 125, 95 and 40/37 kD proteins
which was mediated by upstream cyclo- and lipoxygenases. The phosphorylated proteins were localized to the cortical actin-stress
fiber attachment zones in situ by confocal microscopy. On the other hand, AMF receptor activation induced significant decrease
in overall serine-phosphorylation level of cellular proteins accompanied by serine phosphorylation of 200, 90, 78 and 65 kd
proteins. The decrease in serine phosphorylation was independent of PTKs, PKC as well as cyclo- and lipoxygenases. However,
AMF induced robust translocation of PKCα to the stress fibers and cortical actin suggesting a critical role for this kinase
in the generation of the motility signal. Based on the significant decrease in serine phosphorylation after AMF stimulus in
B16a cells we postulated the involvement of putative serine/threonine phosphatase(s) upstream lipoxygenase and activation
of the protein tyrosine kinase cascade downstream cyclo- and lipoxygenase(s) in the previously identified autocrine motility
signal.
This revised version was published online in July 2006 with corrections to the Cover Date. 相似文献
143.
S A Ford E R Tovey B A Baldo 《International archives of allergy and applied immunology》1985,78(1):15-21
Orchard grass (cocksfoot) pollen extracts, fractionated by polyacrylamide gradient electrophoresis or SDS gel electrophoresis were electroblotted onto nitrocellulose membranes and probed with sera from orchard grass pollen-allergic patients and 125I-anti-human IgE. The IgE-binding components of the pollen were detected by autoradiography. Elution studies showed that allergens could be extracted immediately and continuously over a 3-hour period. Two fractions of MWs 28,000 and 30,000 could be detected only after 20 min extraction. SDS-PAGE separations gave the better resolution revealing 19 electrophoretically-separate components, 13 of which bound human IgE. All of the IgE-binding components had MWs in the range 14,000 - 70,000. Three of the bands bound IgE from more than 85% of the serum samples. Following gradient gel electrophoresis, IgE binding was exhibited by 10 bands in the range MW 5,000 to greater than 669,000. The technique used allows one to quantitatively examine patients' sera for allergen-specific IgE antibodies and to identify the clinically important allergens. Results revealed numerous allergenic components over a wide MW range while patterns of IgE binding with different patients' sera demonstrated a great diversity of IgE antibody responses. This study demonstrates the suitability of the electroblotting technique combined with autoradiography for the investigation of allergenic components of grass pollen extracts and hence has application to extract standardization and immunotherapy. Such studies can be carried out rapidly, economically and with a high degree of sensitivity. 相似文献
144.
Rademakers R Melquist S Cruts M Theuns J Del-Favero J Poorkaj P Baker M Sleegers K Crook R De Pooter T Bel Kacem S Adamson J Van den Bossche D Van den Broeck M Gass J Corsmit E De Rijk P Thomas N Engelborghs S Heckman M Litvan I Crook J De Deyn PP Dickson D Schellenberg GD Van Broeckhoven C Hutton ML 《Human molecular genetics》2005,14(21):3281-3292
145.
The current view of whisker movement is that approximately 25 whiskers on each side of the face move in synchrony. To determine whether whiskers are constrained to move together, we trained rats to use two whiskers on the same side of the face in simple behavioral tasks and videotaped the whiskers during the task. Here we report that the movement of adjacent whiskers is usually synchronous but can diverge: 1) the distance between whiskers can vary dramatically during movement; 2) one whisker can move while the second one remains stationary; 3) two whiskers can simultaneously move in opposite directions; and 4) one whisker can be maintained in contact with an object while the other is retracted and protracted. The frequency of whisker movement during the task falls within the previously reported range for rats whisking freely into air or performing roughness discrimination with their whiskers. Our data also suggest that whisker movement can be divided into three distinct phases: protraction, retraction, and a measurable delay between these movements. We conclude that, although whiskers often move in concert, adjacent caudal whiskers can be moved independently of each other. 相似文献
146.
Linkage of chromosome 13q32 to schizophrenia in a large veterans affairs cooperative study sample 总被引:3,自引:0,他引:3
Faraone SV Skol AD Tsuang DW Bingham S Young KA Prabhudesai S Haverstock SL Mena F Menon AS Bisset D Pepple J Sautter F Baldwin C Weiss D Collins J Keith T Boehnke M Tsuang MT Schellenberg GD 《American journal of medical genetics》2002,114(6):598-604
Several prior reports have suggested that chromosomal region 13q32 may harbor a schizophrenia susceptibility gene. In an attempt to replicate this finding, we assessed linkage between chromosome 13 markers and schizophrenia in 166 families, each with two or more affected members. The families, assembled from multiple centers by the Department of Veterans Affairs Cooperative Studies Program, included 392 sampled affected subjects and 216 affected sib pairs. By DSM-III-R criteria, 360 subjects (91.8%) had a diagnosis of schizophrenia and 32 (8.2%) were classified as schizoaffective disorder, depressed. The families had mixed ethnic backgrounds. The majority were northern European-American families (n = 62, 37%), but a substantial proportion were African-American kindreds (n = 60, 36%). Chromosome 13 markers, spaced at intervals of approximately 10 cM over the entire chromosome and 2-5 cM for the 13q32 region were genotyped and the data analyzed using semi-parametric affected only linkage analysis. For the combined sample (with race broadly defined and schizophrenia narrowly defined) the maximum LOD score was 1.43 (Z-score of 2.57; P = 0.01) at 79.0 cM between markers D13S1241 (76.3 cM) and D13S159 (79.5 cM). Both ethnic groups showed a peak in this region. The peak is within 3 cM of the peak reported by Brzustowicz et al. [1999: Am J Hum Genet 65:1096-1103]. 相似文献
147.
William E Berger Linda B Ford Todd Mahr Robert A Nathan Courtney Crim Lisa Edwards Donna S Wightman William R Lincourt Kathleen Rickard 《Annals of allergy, asthma & immunology》2002,89(4):393-399
BACKGROUND: Studies have shown fluticasone propionate (FP) 100, 200, and 500 microg administered once daily to be effective in the treatment of asthma. The efficacy of a once daily regimen of FP 250 microg has not been evaluated previously. OBJECTIVE: We sought to evaluate the efficacy and safety of inhaled FP 250 microg administered once daily in patients currently receiving inhaled short-acting beta-agonists (SABA) alone or inhaled corticosteroids (ICS). METHODS: In two separate studies, 408 patients in the SABA study and 401 patients in the ICS study were randomly assigned to receive FP 250 microg or placebo for 12 weeks through the Diskus device (GlaxoSmithKline, Research Triangle Park, NC) each morning. RESULTS: At the study endpoint, SABA patients treated with FP and placebo had mean increases in forced expiratory volume in 1 second from baseline of 0.23 +/- 0.03 L and 0.10 +/- 0.03 L, respectively (P < 0.001). ICS patients treated with FP had a mean increase of 0.08 +/- 0.02 L compared with a decrease in forced expiratory volume in 1 second of -0.08 +/- 0.03 L with placebo (P < 0.001). Changes of similar magnitude in morning peak expiratory flow rates were seen with FP in both the SABA and ICS studies. Fewer FP-treated ICS study patients were withdrawn from the study as a result of predetermined asthma stability criteria and, therefore, those patients had a greater probability of remaining in the study than placebo-treated patients (P < 0.001). CONCLUSIONS: FP 250 microg, once daily, produced greater improvements in pulmonary function and asthma symptom control than placebo. This new treatment regimen provides clinicians with an additional therapeutic option for patients with asthma previously treated with either beta2-agonists alone or ICS. 相似文献
148.
Ferdinand von Meyenn Martin Schaefer Heike Weighardt Stefan Bauer Carsten J. Kirschning Hermann Wagner Tim Sparwasser 《Immunobiology》2006,211(6-8):557
Recognition of mycobacteria by the innate immune system is essential for the development of an adaptive immune response. Mycobacterial antigens stimulate antigen presenting cells (APCs) through distinct Toll-like receptors (TLRs) resulting in rapid activation of the innate immune system. The role of TLRs during infection with Mycobacterium bovis Bacillus Calmette-Guérin (BCG) has been evaluated for TLR2 and TLR4 only. Surprisingly, despite the fact that immune stimulatory CpG-motifs have been originally derived from BCG, for the vaccine strain the role of TLR9 has not been addressed before. To identify the set of TLRs involved in the recognition of BCG, we infected bone marrow-derived macrophages and bone marrow-derived dendritic cells (Flt3-ligand generated DCs) from TLR2, TLR3, TLR4, TLR7, TLR9, MyD88 knockout, TLR2/4 and TLR2/4/9 multiple knockout mice. The degree of activation and stimulation was determined by TNFα, IL-6 and IL-12p40 ELISA. Activation of DCs was measured by surface expression of the costimulatory molecule CD86. We observed the most dramatic reduction of the inflammatory response for TLR2-deficient antigen presenting cells. Both macrophages and DCs produce markedly decreased amounts of TNFα and IL-6 in the absence of TLR2 whereas no significant reduction could be observed for TLR3, 4, 7, 9 single TLR-knockouts. However, IL-12 production in DCs appears not exclusively dependent on TLR2 and only in TLR2/4/9-deficient DCs BCG-induced IL-12 is reduced to background levels. Similarly, up-regulation of CD86 is abolished only in TLR2/4/9-deficient DCs supporting a role of TLR9 in the recognition of M. bovis BCG by murine dendritic cells. 相似文献
149.
BACKGROUND: The latent structure of depression was examined using taxometric analysis, a family of statistical procedures designed specifically to test whether a given construct is best conceptualized as a distinct category or a continuous dimension. METHOD: Data were derived from the Australian National Survey of Mental Health and Well-Being, a large epidemiological survey that measured the prevalence of the major DSM-IV and ICD-10 mental disorders. Two taxometric procedures, maximum covariance (MAXCOV) and mean above minus below a cut (MAMBAC), were carried out on a sample of 1933 community volunteers. Simulated categorical and dimensional datasets aided in the interpretation of the research data. RESULTS: The results of the taxometric analyses in the subsample who endorsed at least one symptom of depression were consistent with a dimensional latent structure of depression. CONCLUSIONS: The findings of the current study suggest that depression, as measured in this subsample, is best conceptualized, measured and classified as a continuously distributed syndrome rather than as a discrete diagnostic entity. Incorporation of dimensional measurement into psychiatric classification systems remains a challenge for the future. 相似文献
150.
A re-examination of ryegrass (Lolium perenne) pollen allergens 总被引:4,自引:0,他引:4
Electroblotting of crude ryegrass pollen extracts and purified group I, II and III allergens identified 14 IgE-binding components, 8 of which were previously unrecognized. In addition to allergen groups I, II and III, which are already regarded as clinically important, and on the basis of the frequencies and intensities of IgE binding with sera from 42 ryegrass pollen-allergic patients, proteins with molecular weights (MWs) of 60, 32, 30 and 28 kD were identified as allergens of possible major clinical importance. Six other pollen components with MWs ranging from 23 to 80 kD and which reacted with IgE antibodies in the sera of 33-50% of patients, should also be viewed as proteins with potential clinical relevance for at least a proportion of the patients. The electrophoretic separation patterns of ryegrass pollen extracts in both alkaline and acid gels and IgE-probed membrane transfers produced in this study should serve as useful reference patterns for standardization purposes. In addition, the identification of the complete allergen recognition pattern by individual patients will permit safer and more effective diagnosis and therapy of ryegrass pollen sensitivities. 相似文献