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81.
Hercus TR; Cambareri B; Dottore M; Woodcock J; Bagley CJ; Vadas MA; Shannon MF; Lopez AF 《Blood》1994,83(12):3500-3508
Residues within the first and fourth helices of human granulocyte- macrophage colony-stimulating factor (hGM-CSF) were analyzed for their role in biologic activity and interaction with the alpha- and beta- chains of the hGM-CSF receptor. Within the first helix substitution of the surface residues Glu14, Asn17, Gln20, Arg23, Arg24, and Asn27 or the buried residues Ala18, Leu25, and Leu28 did not significantly impair bioactivity or receptor binding. Substitutions at the buried residues Ala22 and Leu26 had intermediate bioactivity. However, substitutions of the surface residue Glu21 or the buried residue Ile19 reduced the relative bioactivity of the analogues to as little as 0.45% and 0.3%, respectively. Substitution of the charged surface residues of the fourth helix showed that substitution at Glu104, Lys107, and Lys111 had no significant effect on bioactivity, but substitution at Glu108 and Asp112 reduced the potency of the analogues to 34% and 7%, respectively. Receptor binding studies showed that, whereas Glu21 is the critical residue for binding to the hGM-CSF-receptor beta-chain, Asp112 is likely to be involved in binding to the GM-CSF-receptor alpha- chain. These results establish the relative contribution of residues in the first and fourth helices for GM-CSF bioactivity and receptor binding, and support a model where the fourth helix of GM-CSF interacts with the alpha-chain, and the first helix with the beta-chain of the GM- CSF receptor. 相似文献
82.
Denise R Silva Diego M Menegotto Luis F Schulz Marcelo B Gazzana Paulo TR Dalcin 《BMC infectious diseases》2010,10(1):54
Background
To describe the characteristics of patients with tuberculosis (TB) requiring intensive care and to identify the factors that predicts in-hospital mortality in a city of a developing country with intermediate-to-high TB endemicity. 相似文献83.
BackgroundLocked pubic symphysis is an unusual form of pelvic injury. In this the intact pubis gets trapped against contralateral pubis. Closed reduction can be attempted though often requires open reduction and internal fixation. This paper is presented for its rarity and probably first case series on locked pubic symphysis from single institute.Materials and methodsThree cases are presented from the Institute of Orthopaedics and Traumatology, Government General Hospital and Madras Medical College, Chennai from February 2007 to July 2009. Initially closed reduction was attempted but was not possible, so open reduction was planned. Open reduction was successful in all cases with some difficulty and fixed with symphysial plating. All patients were followed up for functional outcome for a mean follow-up of 15 months.DiscussionThis is the first time in the literature a case series of locked pubic symphysis is presented. In all cases it was found that anterior superior iliac spine on the affected side had moved closer to the midline compared to the opposite side. Though suprapubic cystostomy is a contraindication for pfannensteil incision, we have reduced three cases by this incision and done internal fixation with no postoperative wound infection. We were able to reduce the locked pubis with simple maneuvers and with no special distraction instruments. We did not require any osteotomy for the reduction which is a disadvantage as it may produce healing problems.ConclusionLocked pubic symphysis is a rare form of pelvic injury. Though conservative closed reduction maneuvers have been described open reduction is often required. Internal fixation helps not only in stabilizing the anterior rim of pelvis but also the posterior aspect by stabilizing the sacro iliac joint which improves pelvic stability and promotes recovery. 相似文献
84.
EG Gkougkousis M Khan TR Terry JK Mellon 《Annals of the Royal College of Surgeons of England》2009,91(6):532-534
Three cases of recurrent post-coital haematuria are described. Extensive protracted investigations pinpointed urethral varicosities as the likely cause. All patients were successfully treated with diathermy fulguration. 相似文献
85.
86.
Rachel C. Angers Tanya S. Seward Dana Napier Michael Green Edward Hoover Terry Spraker Katherine O’Rourke Aru Balachandran Glenn C. Telling 《Emerging infectious diseases》2009,15(5):696-703
Chronic wasting disease (CWD) is a contagious, fatal prion disease of deer and elk that continues to emerge in new locations. To explore the means by which prions are transmitted with high efficiency among cervids, we examined prion infectivity in the apical skin layer covering the growing antler (antler velvet) by using CWD-susceptible transgenic mice and protein misfolding cyclic amplification. Our finding of prions in antler velvet of CWD-affected elk suggests that this tissue may play a role in disease transmission among cervids. Humans who consume antler velvet as a nutritional supplement are at risk for exposure to prions. The fact that CWD prion incubation times in transgenic mice expressing elk prion protein are consistently more rapid raises the possibility that residue 226, the sole primary structural difference between deer and elk prion protein, may be a major determinant of CWD pathogenesis. 相似文献
87.
TR Miller I Milicic J Bauch J Du B Surber KE Browman K Marsh M Cowart JD Brioni TA Esbenshade 《British journal of pharmacology》2009,157(1):139-149
Background and purpose:
The histamine H3 receptor antagonist radioligand [3H]-A-349821 was characterized as a radiotracer for assessing in vivo receptor occupancy by H3 receptor antagonists that affect behaviour. This model was established as an alternative to ex vivo binding methods, for relating antagonist H3 receptor occupancy to blood levels and efficacy in preclinical models.Experimental approach:
In vivo cerebral cortical H3 receptor occupancy by [3H]-A-349821 was determined in rats from differences in [3H]-A-349821 levels in the isolated cortex and cerebellum, a brain region with low levels of H3 receptors. Comparisons were made to relate antagonist H3 receptor occupancy to blood levels and efficacy in a preclinical model of cognition, the five-trial inhibitory avoidance response in rat pups.Key results:
In adult rats, [3H]-A-349821, 1.5 µg·kg−1, penetrated into the brain and cleared more rapidly from cerebellum than cortex; optimally, [3H]-A-349821 levels were twofold higher in the latter. With increasing [3H]-A-349821 doses, cortical H3 receptor occupancy was saturable with a binding capacity consistent with in vitro binding in cortex membranes. In studies using tracer [3H]-A-349821 doses, ABT-239 and other H3 receptor antagonists inhibited H3 receptor occupancy by [3H]-A-349821 in a dose-dependent manner. Blood levels of the antagonists corresponding to H3 receptor occupancy were consistent with blood levels associated with efficacy in the five-trial inhibitory avoidance response.Conclusions and implications:
When employed as an occupancy radiotracer, [3H]-A-349821 provided valid measurements of in vivo H3 receptor occupancy, which may be helpful in guiding and interpreting clinical studies of H3 receptor antagonists. 相似文献88.
Janey Prodoehl PT PhD Mathew Spraker PhD Daniel Corcos PhD Cynthia Comella MD David Vaillancourt PhD 《Movement disorders》2010,25(13):2035-2043
To aid the development of symptomatic and disease modifying therapies in Parkinson's disease (PD), there is a strong need to identify noninvasive measures of basal ganglia (BG) function that are sensitive to disease severity. This study examines the relation between blood oxygenation level–dependent (BOLD) activation in every nucleus of the BG and symptom‐specific disease severity in early stage de novo PD. BOLD activation measured at 3 T was compared between 20 early stage de novo PD patients and 20 controls during an established precision grip force task. In addition to the BG nuclei, activation in specific thalamic and cortical regions was examined. There were three novel findings. First, there were significant negative correlations between total motor Unified PD Rating Scale and BOLD activation in bilateral caudate, bilateral putamen, contralateral external segment of the globus pallidus, bilateral subthalamic nucleus, contralateral substantia nigra, and thalamus. Second, bradykinesia was the symptom that most consistently predicted BOLD activation in the BG and thalamus. Also, BOLD activation in the contralateral internal globus pallidus was related to tremor. Third, the reduced cortical activity in primary motor cortex and supplementary motor area in de novo PD did not relate to motor symptoms. These findings demonstrate that BOLD activity in nuclei of the BG relates most consistently to bradykinesia and functional magnetic resonance imaging has strong potential to serve as a noninvasive marker for the state of BG function in de novo PD. © 2010 Movement Disorder Society 相似文献
89.
V Thulasiraman TR Ramesh Pandian S Cheralathan S Ashok 《Indian Journal of Orthopaedics》2010,44(4):471-473
Idiopathic internal jugular phlebectasia, occurs either unilaterally or bilaterally affecting the internal jugular vein is a rare congenital variation often diagnosed during childhood. It usually presents with a benign swelling over the lateral side of neck on the affected side, seen on exertion. A-30-year old male was operated for anterior cervical dissectomy from right lateral approach and was diagnosed per-operatively as internal jugular phlebectasia. The surgery was abandoned at this stage on the advice of cardiothoracic surgeon to investigate the patient for the secondary etiological factors for internal jugular vein dilatation. The patient was reassured without any active intervention for the phlebectasia and cervical dissectomy was performed in the second surgery through the lateral approach from left side. This case is presented in view of rarity and suggested that during preoperative workup the nearby structures like carotid sheath should be evaluated by magnetic resonance imaging to avoid such per-operative surprises. 相似文献
90.
TR Villa AR Correa Moutran LA Sobirai Diaz MM Pereira Pinto FA Carvalho AA Gabbai & D de Souza Carvalho 《Cephalalgia : an international journal of headache》2009,29(6):631-634
The aim of this study was to evaluate the visual attention of children with migraine and compare it with a control group. Thirty migrainous children and 30 controls without headache were subjected to a visual attention assessment with Trail Making Tests (TMT) A/B, Letter Cancellation Test, and the Brazilian computerized test Visual Attention Test, third edition. The migraine group was evaluated after 2 days without headache. The migraine group had an inferior performance compared with the control group on TMT A ( P = 0.03) and B ( P = 0.001), and more errors on tasks 1 ( P = 0.032) and 2 ( P = 0.015) of the Visual Attention Test, presenting difficulty with selective and alternate attention. Attention is a neurological function that depends on structures such as the brainstem, cerebral cortex and the limbic system and on neurotransmitters such as dopamine and noradrenaline. The neurochemical aspects involved in the physiopathology of migraine and attention mechanisms probably predispose these children to visual attention deficits. 相似文献