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111.
The in vitro and animal model studies on optimal dosage of the newer beta-lactams are summarized and put into historical perspective. They provide a rationale for dosage schedules that continuously maintain inhibitory serum and tissue concentrations throughout the dosage interval. In vitro studies on the post-antibiotic effect (PAE) with beta-lactams revealed only short time periods of post-antibiotic growth suppression with gram-positive cocci and no post-antibiotic effect with gram-negative bacilli. A smilar lack of persistent growth suppression was observed with beta-lactams in a neutropenic mouse thigh infection model for both gram-positive and gram-negative bacteria. In the same animal model, dosing regimens of beta-lactams which continuously provided serum concentrations above the MIC were more efficacious than those that did not. The newer third-generation cephalosporins have prolonged half-lives and can maintain serum levels above the MIC for most pathogens, even when dosed at widely spaced intervals. 相似文献
112.
Virtual auditory space (VAS) stimuli based on outer ear transfer functions became increasingly important in spatial hearing research. However, few studies have investigated the match between responses of auditory neurons to VAS and free-field (FF) stimulation. This study validates acoustic spatial receptive fields (SRFs) of 183 individual midbrain units using both VAS and FF stimuli. The first-spike latency, which varied systematically across SRFs, was 14.9 +/- 8.3 (SD) ms in FF, and 15.1 +/- 8.3 ms in VAS. Spike-count-based SRFs measured 0-20 dB above the neural threshold covered on average 44.5 +/- 18.0% of the recorded sphere in FF and 45.5 +/- 18.7% in VAS. The average deviation of the centroid position of SRFs using FF and VAS stimuli was 7.4 degrees azimuth and 3.3 degrees elevation. The average spike rate remained unchanged. The SRF overlap recorded using FF and VAS stimuli (mean: 71.3 +/- 12.6%) or repeated FF stimuli (70.2 +/- 14.2%) was high and strongly correlated (r = 0.96; P < 0.05). The SRF match observed with FF and VAS stimuli was not significantly altered over a range of stimulus levels (paired t-test P = 0.51; n = 6). Randomized VAS barely affected SRF sizes, centroids, or maximum spike count but decreased the average minimum response to 59% compared with sequential stimulation (paired t-test; P = 0.05; n = 26). SRF recordings in VAS excluding the acoustic distortions of the recording equipment differed from those in VAS incorporating the equipment (paired t-test P = 0.01; n = 5). In conclusion, neurophysiological recordings demonstrate that individualized VAS stimuli provided a good simulation of a FF environment. 相似文献
113.
Self-contained underwater breathing apparatus (scuba) diving has grown in popularity, with nearly 9 million sport divers in
the United States alone. Approximately 7% of the population has been diagnosed with asthma, which is similar to the percentage
of divers admitting they have asthma. Numerous concerns exist regarding subjects with asthma who choose to participate in
recreational diving. Among these concerns are pulmonary barotrauma, pneumomediastinum, pneumothorax, arterial gas embolism,
ear barotrauma, sinus barotrauma, and dental barotrauma. Despite these concerns, a paucity of information exists linking asthma
to increased risk of diving complications. However, it has long been the norm to discourage individuals with asthma from participating
in recreational scuba diving. This article examines the currently available literature to allow for a more informed decision
regarding the possible risks associated with diving and asthma. It examines the underlying physiological principles associated
with diving, including Henry’s law and Boyle’s law, to provide a more intimate understanding on physiological changes occurring
in the respiratory system under compressive stress. Finally, this article offers a framework for guiding the patient with
asthma who is interested in scuba diving. Under the right circumstances, the patient with asthma can safely participate in
recreational diving without apparent increased risk of an asthma-related event. 相似文献
114.
Sarah Curran Shaun Purcell Ian Craig Philip Asherson Pak Sham 《American journal of medical genetics. Part B, Neuropsychiatric genetics》2005,(1):42-47
Molecular studies of attention deficit hyperactivity disorder (ADHD) have identified susceptibility genes for the categorically diagnosed disorder using operational diagnostic criteria. Here, we take a QTL approach to mapping genes for ADHD using a composite continuous index of ADHD behavior in a large epidemiological sample. Previous studies of clinical ADHD suggest that two functional polymorphisms in the serotonin transporter gene (SLC6A4), one in the 5'-regulatory region of the gene (5-HTTLPR) and the other a VNTR (5-HTTVNTR) in the second intron, as well as a single nucleotide polymorphism in the 3'-untranslated region (3'-UTR SNP), may be associated with the disorder. Here, we investigate these polymorphisms as well as an additional ten SNPs spread across the gene. We found significant association with the long (L) allele of the 5-HTTLPR; P = 0.019, but neither the 5-HTTVNTR nor the 3'-UTR SNP were significantly associated. Significant associations (P < 0.05) were found for a further 5 the 10 other markers tested. We found evidence for two haplotype blocks spanning the region. We found strong evidence for association with the first haplotype block (comprised of four markers), with the significance of a combined primary and secondary test of association reaching an empirical P value = 0.0054 for the global test and an empirical P value = 0.00081 for the largest local test. Thus, we show here that SLC6A4, which has a major influence on brain serotonin availability, may be a QTL for ADHD. 相似文献
115.
Therapy for rhinitis improves sleep quality and symptoms of daytime sleepiness. This improvement with therapy may be secondary to anti-inflammatory effects, leading to a reduction of inflammatory mediators, or to a mechanical reduction of congestion directly leading to improvement in sleep disturbance. We combined our data from 3 placebo-controlled studies of intranasal corticosteroids in patients with perennial rhinitis to determine whether a correlation between the reduction of congestion and improved sleep and daytime somnolence existed. The pooled data of budesonide, flunisolide, and fluticasone demonstrated significantly decreased nasal congestion, sleep problems, and sleepiness in treated patients. The data demonstrated a correlation between a reduction in nasal congestion and an improvement of sleep (P < .01) and daytime somnolence (P = .01). Thus, topical intranasal corticosteroids should be used to decrease nasal congestion and to improve sleep and daytime somnolence in patients manifesting these symptoms. 相似文献
116.
We investigated the effects of 5-hydroxytryptamine (5-HT, serotonin) in striatal cholinergic interneurones with gramicidin-perforated whole-cell patch recordings. Bath-application of serotonin (30 μ m ) significantly and reversibly increased the spontaneous firing rate of 37/45 cholinergic interneurones tested. On average, in the presence of serotonin, firing rate was 273 ± 193% of control. Selective agonists of 5-HT1A , 5-HT3 , 5-HT4 and 5-HT7 receptors did not affect cholinergic interneurone firing, while the 5-HT2 receptor agonist α-methyl-5-HT (30 μ m ) mimicked the excitatory effects of serotonin. Consistently, the 5-HT2 receptor antagonist ketanserin (10 μ m ) fully blocked the excitatory effects of serotonin. Two prominent after-hyperpolarizations (AHPs), one of medium duration that was apamin-sensitive and followed individual spikes, and one that was slower and followed trains of spikes, were both strongly and reversibly reduced by serotonin; these effects were fully blocked by ketanserin. Conversely, the depolarizing sags observed during negative current injections and mediated by hyperpolarization-activated cationic currents were not affected. In the presence of apamin and tetrodotoxin, the slow AHP was strongly reduced by 5-HT, and fully abolished by the calcium channel blocker nickel. These results show that 5-HT exerts a powerful excitatory control on cholinergic interneurones via 5-HT2 receptors, by suppressing the AHPs associated with two distinct calcium-activated potassium currents. 相似文献
117.
Survey of the Distribution of a Newly Characterized Receptor for Advanced Glycation End Products in Tissues 总被引:33,自引:2,他引:33 下载免费PDF全文
Jerold Brett Ann Marie Schmidt Shi Du Yan Yu Shan Zou Elliott Weidman David Pinsky Roman Nowygrod Michael Neeper Craig Przysiecki Alan Shaw Antonio Migheli David Stern 《The American journal of pathology》1993,143(6):1699-1712
Advanced glycation end products (AGEs), the final products of nonenzymatic glycation and oxidation of proteins, are found in the plasma and accumulate in the tissues during aging and at an accelerated rate in diabetes. A novel integral membrane protein, termed receptor for AGE (RAGE), forms a central part of the cell surface binding site for AGEs. Using monospecific, polyclonal antibody raised to human recombinant and bovine RAGE, immunostaining of bovine tissues showed RAGE in the vasculature, endothelium, and smooth muscle cells and in mononuclear cells in the tissues. Consistent with these data, RAGE antigen and mRNA were identified in cultured bovine endothelium, vascular smooth muscle, and monocyte-derived macrophages. RAGE antigen was also visualized in bovine cardiac myocytes as well as in cultures of neonatal rat cardiac myocytes and in neural tissue where motor neurons, peripheral nerves, and a population of cortical neurons were positive. In situ hybridization confirmed the presence of RAGE mRNA in the tissues, and studies with rat PC12 pheochromocytes indicated that they provide a neuronal-related cell culture model for examining RAGE expression. Pathological studies of human atherosclerotic plaques showed infiltration of RAGE-expressing cells in the expanded intima. These results indicate that RAGE is present in multiple tissues and suggest the potential relevance of AGE-RAGE interactions for modulating properties of the vasculature as well as neural and cardiac function, prominent areas of involvement in diabetes and in the normal aging process. 相似文献
118.
Summary We have used physicochemical and ultrastructural methods to investigate the effects of Ca2+ and ATP on the structure of purified heavy meromyosin (HMM) from the striated adductor muscle of the scallop, a species with myosin-linked regulation. Using papain as a structural probe, we found that, in the presence of ATP, the head/tail junction was five times more susceptible to digestion at high levels of Ca2+ than at low levels.wBy HPLC gel filtration, two fractions of scallop HMM with different Stokes radii were detected in the presence of ATP at low Ca2+, while at high Ca2+ a single peak with the larger Stokes radius predominated. Electron microscopy of rotary-shadowed HMM suggested that molecules with the smaller Stokes radius had their heads bent back towards their tails, while those with the larger radius had heads pointing away from the tail. The number of molecules with their heads bent back decreased at high Ca2+ levels. The data also showed that in the absence of ATP or at high salt, HMM molecules behaved similarly to those in the presence of ATP at high Ca2+.These results suggest that scallop myosin heads can exist in two conformations (heads down towards the tail and heads up away from the tail) and that the equilibrium between these two conformations is altered by the concentrations of salt, ATP and Ca2+. However, the equilibrium between the two forms appears to be too slow to be involved in regulating contraction. The heads-down configuration may instead be related to the inactive, folded (10S) form of scallop myosin and possibly involved in filament assembly during development. 相似文献
119.
Peter H. Cooke Fredric S. Fay Roger Craig 《Journal of muscle research and cell motility》1989,10(3):206-220
Summary The structure of myosin filaments isolated from skinned toad stomach smooth muscle cells has been examined by electron microscopy as a step toward identifying thein vivo structure. When negatively stained following exposure to relaxing conditions, the filaments exhibited a continuous 14-nm axial repeat of crossbridge projections with no central bare zone. The filaments thus differed from the bipolar filaments found in striated muscle and displayed instead features resembling side-polar and mixed-polarity filament models. By rotation of isolated filaments around their longitudinal axes it was found that cross bridges occurred only along two sides of the filament, an arrangement consistent with the side-polar but not the mixed-polarity model. The polarity is thus similar to that proposed for ribbons (Small & Squire,J. molec. Biol.
67, (1972) 17–149) and for synthetic smooth muscle myosin filaments (Craig and Megerman,J. Cell Biol.
75, (1977) 990–996); their appearance in cross-section, however, shows that these structures are filaments (i.e. with two axes of similar dimensions) and not broad ribbons. As the filaments were derived directly from skinned cells which contracted and relaxed in response to physiological levels of MgATP and Ca2+ at rates comparable to those of native, isolated cells, this unusual arrangement of cross bridges appears to be an effective, functional form of myosin in the contractile apparatus. Side-polar filaments therefore merit consideration as plausible candidates for the native organization of myosin in vertebrate smooth muscle cells. 相似文献
120.
Pendergast D Zamparo P di Prampero PE Capelli C Cerretelli P Termin A Craig A Bushnell D Paschke D Mollendorf J 《European journal of applied physiology》2003,90(3-4):377-386
In this paper a complete energy balance for water locomotion is attempted with the aim of comparing different modes of transport in the aquatic environment (swimming underwater with SCUBA diving equipment, swimming at the surface: leg kicking and front crawl, kayaking and rowing). On the basis of the values of metabolic power (Ė), of the power needed to overcome water resistance (d) and of propelling efficiency (P=d/tot, where tot is the total mechanical power) as reported in the literature for each of these forms of locomotion, the energy cost per unit distance (C=Ė/v, where v is the velocity), the drag (performance) efficiency (d=d/Ė) and the overall efficiency (o=tot/Ė=d/P) were calculated. As previously found for human locomotion on land, for a given metabolic power (e.g. 0.5 kW=1.43 l·min–1 O2) the decrease in C (from 0.88 kJ·m–1 in SCUBA diving to 0.22 kJ·m–1 in rowing) is associated with an increase in the speed of locomotion (from 0.6 m·s–1 in SCUBA diving to 2.4 m·s–1 in rowing). At variance with locomotion on land, however, the decrease in C is associated with an increase, rather than a decrease, of the total mechanical work per unit distance (Wtot, kJ·m–1). This is made possible by the increase of the overall efficiency of locomotion (o=tot/Ė=Wtot/C) from the slow speeds (and loads) of swimming to the high speeds (and loads) attainable with hulls and boats (from 0.10 in SCUBA diving to 0.29 in rowing). 相似文献