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Conclusions 1. Acute pulmonary histoplasmosis in adults is demonstrated to be associated with exogenous sources of infection in one-half of a series of cases. 2. No exogenous sources of infection were found in chronic pulmonary histoplasmosis in adults by methods comparable to those used in acute pulmonary histoplasmosis. 3. The significance of these findings for the pathogenesis of the three clinical forms of histoplasmosis is discussed. 4. In acute pulmonary histoplasmosis in adults, the isolation ofH. capsulatum from the environment at sites of exposure aided in specific diagnosis.Two acute pulmonary histoplasmosis cases were reported previously (2–3).  相似文献   
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alpha 1-Proteinase inhibitor (alpha 1-PI), a member of the serineproteinase inhibitor superfamily, has a primary role in controllingneutrophil elastase activity within the mammalian circulation. Severalstudies have indicated that the reactive center region of alpha 1-PI, theamino acid sequence of which is critical to recognition of and binding totarget proteinases, is highly divergent within and among species. Thisappears to be a consequence of accelerated rates of evolution that may havebeen driven by positive Darwinian selection. In order to examine this andother features of alpha 1-PI evolution in more detail, we have isolated andsequenced cDNAs representing alpha 1- PI mRNAs of the mouse species Mussaxicola and Mus minutoides and have compared these with a number of othermammalian alpha 1-PI mRNAs. Relative to other mammalian mRNAs, the extentof nonsynonymous substitution is generally high throughout the alpha 1-PImRNA molecule, indicating greater overall rates of amino acid substitution.Within and among mouse species, the 5'-half of the mRNA, but not the3'-half, has been homogenized by concerted evolution. Finally, the reactivecenter is under diversifying or positive Darwinian selection in muridrodents (rats, mice) and guinea pigs yet is under purifying selection inprimates and artiodactyls. The significance of these findings to alpha 1-PIfunction and the possible selective forces driving evolution of serpins ingeneral are discussed.  相似文献   
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  总被引:4,自引:0,他引:4  
In congestive heart failure (CHF), themechanisms of exercise-induced sympathoexcitation are poorly defined.We compared the responses of sympathetic nerve activity directed tomuscle (MSNA) and to skin (SSNA, peroneal microneurography) duringrhythmic handgrip (RHG) at 25% of maximal voluntary contraction andduring posthandgrip circulatory arrest (PHG-CA) in CHF patients with those of an age-matched control group. During RHG, the CHF patients fatigued prematurely. At end exercise, the increase in MSNA was similarin both groups (CHF patients, n = 12;controls, n = 10). However, duringPHG-CA, in the controls MSNA returned to baseline, whereas it remainedelevated in CHF patients (P < 0.05).Similarly, at end exercise, the increase in SSNA was comparable in bothgroups (CHF patients, n = 11;controls, n = 12), whereas SSNAremained elevated during PHG-CA in CHF patients but not in the controls (P < 0.05). In a separate controlgroup (n = 6), even high-intensity static handgrip was not accompanied by sustained elevation of SSNAduring PHG-CA. 31P-nuclear magneticresonance spectroscopy during RHG demonstrated significant muscleacidosis and accumulation of inorganic phosphate in CHF patients(n = 7) but not in controls(n = 9). We conclude that in CHFpatients rhythmic forearm exercise leads to premature fatigue andaccumulation of muscle metabolites. The prominent PHG-CA response ofMSNA and SSNA in CHF patients suggests activation of the musclemetaboreflex. Because, in contrast to controls, in CHF patients bothMSNA and SSNA appear to be under muscle metaboreflex control, themechanisms and distribution of sympathetic outflow during exerciseappear to be different from normal.

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Betchen  SA; Doty  RL 《Chemical senses》1998,23(4):453-457
Several fundamental questions remain enigmatic concerning human olfactorysensitivity, including (i) whether detection threshold differences existbetween the two sides of the nose (and, if so, whether such differences areinfluenced by handedness) and (ii) whether bilateral (i.e. binasal)stimulation leads to lower thresholds than unilateral stimulation (and, ifso, whether the degree of facilitation is inversely related to generalolfactory ability). In this study, and well-validated single staircaseprocedure was used to establish bilateral and unilateral detectionthresholds for the cranial nerve I stimulant phenyl ethyl alcohol in 130right- and 33 left-handed subjects. No differences in sensitivity betweenthe left and right sides of the nose were observed in either group.Bilateral thresholds were lower, on average, than unilateral thresholdswhen the latter were categorized in terms of left and right nares. However,the bilateral thresholds did not differ significantly from those of theside of the nose with the lower threshold. Overall smell ability, asmeasured by the University of Pennsylvania Smell Identification Test, didnot interact with any of the test measures. These data imply that (i) theleft and right sides of the nose do not systematically differ in detectionthreshold sensitivity for either dextrals or sinistrals and (ii) if centralintegration of left:right olfactory threshold sensitivity occurs, itseffects do not exceed the function of the better side of the nose.  相似文献   
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The CpG Island Methylator Phenotype (CIMP) is fundamental to an important subset of colorectal cancer; however, its cause is unknown. CIMP is associated with microsatellite instability but is also found in BRAF mutant microsatellite stable cancers that are associated with poor prognosis. The isocitrate dehydrogenase 1 (IDH1) gene causes CIMP in glioma due to an activating mutation that produces the 2-hydroxyglutarate oncometabolite. We therefore examined IDH1 alteration as a potential cause of CIMP in colorectal cancer. The IDH1 mutational hotspot was screened in 86 CIMP-positive and 80 CIMP-negative cancers. The entire coding sequence was examined in 81 CIMP-positive colorectal cancers. Forty-seven cancers varying by CIMP-status and IDH1 mutation status were examined using Illumina 450K DNA methylation microarrays. The R132C IDH1 mutation was detected in 4/166 cancers. All IDH1 mutations were in CIMP cancers that were BRAF mutant and microsatellite stable (4/45, 8.9%). Unsupervised hierarchical cluster analysis identified an IDH1 mutation-like methylation signature in approximately half of the CIMP-positive cancers. IDH1 mutation appears to cause CIMP in a small proportion of BRAF mutant, microsatellite stable colorectal cancers. This study provides a precedent that a single gene mutation may cause CIMP in colorectal cancer, and that this will be associated with a specific epigenetic signature and clinicopathological features.  相似文献   
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The Na-K-2Cl cotransporter (NKCC1) is one of several transporters that have been linked to hypertension, and its inhibition reduces vascular smooth muscle tone and blood pressure. NKCC1 in the rat aorta is stimulated by vasoconstrictors and inhibited by nitrovasodilators, and this is linked to the contractile state of the smooth muscle. To determine whether blood pressure also regulates NKCC1, we examined the acute effect of hypertension on NKCC1 in rats after aortic coarctation. In the hypertensive aorta (28-mmHg rise in mean blood pressure), an increase in NKCC1 activity (measured as bumetanide-sensitive (86)Rb efflux) was apparent by 16 h and reached a plateau of 62% greater than control at 48 h. In contrast, there was a slight decrease in NKCC1 activity in the hypotensive aorta (21% decrease in mean blood pressure). Measurement of NKCC1 mRNA by real-time PCR revealed a fivefold increase in the hypertensive aorta compared with the hypotensive aorta or sham aorta. The inhibition by bumetanide of isometric force response to phenylephrine was significantly greater in the hypertensive aorta than in the control aorta or hypotensive aorta. We conclude that NKCC1 in rat aortic smooth muscle is regulated by blood pressure, most likely through changes in transporter abundance. This upregulation of NKCC1 is associated with a greater contribution to force generation in the hypertensive aorta. This is the first demonstration that NKCC1 in vascular smooth muscle is regulated by blood pressure and indicates that this transporter is important in the acute response of vascular smooth muscle to hypertension.  相似文献   
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