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Effects of low-chloride solutions on action potentials of sheep cadiac purkinje fibers 总被引:2,自引:0,他引:2 下载免费PDF全文
The rapid repolarization during phase 1 of the action potential of sheep cardiac purkinje fibers has been attributed to a time- and voltage-dependent chloride current. In part, this conclusion was based on experiments that showed a substantial slowing of phase 1 when larger, presumably impermeant, anions were substituted for chloride in tyrode’s solution. We have re- examined the electrical effects of low-chloride solutions. We recorded action potentials of sheep cardiac purkinje fibers in normal tyrode’s solution and in low-chloride solutions made by substituting sodium propionate, acetylglycinate, methylsulfate, or methanesulfonate for the NaCl of Tyrode’s solution. Total calcium was adjusted to keep calcium ion activity of test solutions equal to that of control solutions. Propionate gave qualitatively variable results in preliminary experiments; it was not tested further. Low-chloride solutions made with the other anions gave much more consistent results: phase 1 and the notch that often occurs between phases 1 and 2 were usually unaffected, and the action potential duration usually increased. The only apparent change in the resting potential was a transient 3-6 mV depolarization when low-chloride solution was first admitted to the chamber, and a symmetrical transient hyperpolarization when chloride was returned to normal. If a time- and voltage-dependent chloride current exists in sheep cardiac purkinje fibers, our results suggest that it plays little role in generating phase 1 of the action potential. 相似文献
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Background
Text-mining can assist biomedical researchers in reducing information overload by extracting useful knowledge from large collections of text. We developed a novel text-mining method based on analyzing the network structure created by symbol co-occurrences as a way to extend the capabilities of knowledge extraction. The method was applied to the task of automatic gene and protein name synonym extraction. 相似文献4.
BACKGROUND: Biochemical testing for pheochromocytoma by measurement of fractionated plasma metanephrines is limited by false positive rates of up to 18% in people without known genetic predisposition to the disease. The plasma normetanephrine fraction is responsible for most false positives and plasma normetanephrine increases with age. The objective of this study was to determine if we could improve the specificity of fractionated plasma measurements, by statistically adjusting for age. METHODS: An age-adjusted metanephrine score was derived using logistic regression from 343 subjects (including 33 people with pheochromocytoma) who underwent fractionated plasma metanephrine measurements as part of investigations for suspected pheochromocytoma at Mayo Clinic Rochester (derivation set). The performance of the age-adjusted score was validated in a dataset of 158 subjects (including patients 23 with pheochromocytoma) that underwent measurements of fractionated plasma metanephrines at Mayo Clinic the following year (validation dataset). None of the participants in the validation dataset had known genetic predisposition to pheochromocytoma. RESULTS: The sensitivity of the age-adjusted metanephrine score was the same as that of traditional interpretation of fractionated plasma metanephrine measurements, yielding a sensitivity of 100% (23/23, 95% confidence interval [CI] 85.7%, 100%). However, the false positive rate with traditional interpretation of fractionated plasma metanephrine measurements was 16.3% (22/135, 95% CI, 11.0%, 23.4%) and that of the age-adjusted score was significantly lower at 3.0% (4/135, 95% CI, 1.2%, 7.4%) (p < 0.001 using McNemar's test). CONCLUSION: An adjustment for age in the interpretation of results of fractionated plasma metanephrines may significantly decrease false positives when using this test to exclude sporadic pheochromocytoma. Such improvements in false positive rate may result in savings of expenditures related to confirmatory imaging. 相似文献
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Genetic affinities of inbred mouse strains of uncertain origin 总被引:5,自引:1,他引:4
Phylogenetic analyses of genetic data arising from 144 gene loci are used
to describe the interrelationships among 24 widely used inbred strains of
mice. An unordered-parsimony analysis gives a cladogram that is virtually
identical to the known genealogy of the mouse strains. A loss-parsimony
analysis is used to evaluate the hypothesis that the observed patterns of
genetic divergence among these 24 strains can be explained by the
segregation of residual heterozygosity arising from a small population of
highly heterozygous mice. The loss-parsimony cladogram is very similar to
both the unordered-parsimony cladogram and the known genealogy of the mice.
The phylogenetic analyses of these 144 loci are integrated with data on the
type and origin of the Y chromosome. Inclusion of the Y-chromosome data
provides additional insights into the genetic composition of several of the
original stocks used to produce the current inbred strains of mice. Ten
strains of uncertain origin are contained in these analyses, including AKR,
BUB, CE, I, NZB, P, RF, SJL, ST, and SWR. SJL is hypothesized to have been
derived from the same Swiss albino stock previously used to produce SWR.
The BUB strain appears to have had a complex origin and shows closest
genetic similarity to SWR and ST. AKR and RF are shown to be closely
related, while the I strain shows greatest genetic similarity to DBA/2 for
the 144 loci. However, I and DBA possess different types of Y chromosome.
The NZB strain shows genetic similarity to several stocks of both U.S. and
European origins. The power of the genetic data used in these analyses
reiterates that inbred strains of mice can be a valuable paradigm for
studies in evolutionary biology.
相似文献
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ADA WRÓBLEWSKA 《Biological journal of the Linnean Society. Linnean Society of London》2012,105(4):761-775
In the last decade a number of studies has illustrated quite different phylogeographical patterns amongst plants with a northern present‐day geographical distribution, spanning the entire circumboreal region and/or circumarctic region and southern mountains. These works, employing several marker systems, have brought to light the complex evolutionary histories of this group. Here I focus on one circumboreal plant species, Chamaedaphne calyculata (leatherleaf), to unravel its phylogeographical history and patterns of genetic diversity across its geographical range. A survey of 29 populations with combined analyses of chloroplast DNA (cpDNA), internal transcribed spacer (ITS) and AFLP markers revealed structuring into two groups: Eurasian/north‐western North American, and north‐eastern North American. The present geographical distribution of C. calyculata has resulted from colonization from two putative refugial areas: east Beringia and south‐eastern North America. The variation of chloroplast DNA (cpDNA) and ITS sequences strongly indicated that the evolutionary histories of the Eurasian/north‐western North American and the north‐eastern North American populations were independent of each other because of a geographical disjunction in the distribution area and ice‐sheet history between north‐eastern and north‐western North America. Mismatch analysis using ITS confirmed that the present‐day population structure is the result of rapid expansion, probably since the last glacial maximum. The AFLP data revealed low genetic diversity of C. calyculata (P = 19.5%, H = 0.085) over the whole geographical range, and there was no evidence of loss of genetic diversity within populations in the continuous range, either at the margins or in formerly glaciated and nonglaciated regions. © 2012 The Linnean Society of London, Biological Journal of the Linnean Society, 2012, 105 , 761–775. 相似文献
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van Halm VP Nurmohamed MT Twisk JW Dijkmans BA Voskuyl AE 《Arthritis research & therapy》2006,8(5):R151-6
Rheumatoid arthritis (RA) is characterized by inflammation and an increased risk for cardiovascular disease (CVD). This study
investigates possible associations between CVD and the use of conventional disease-modifying antirheumatic drugs (DMARDs)
in RA. Using a case control design, 613 RA patients (5,649 patient-years) were studied, 72 with CVD and 541 without CVD. Data
on RA, CVD and drug treatment were evaluated from time of RA diagnosis up to the first cardiovascular event or the end of
the follow-up period. The dataset was categorized according to DMARD use: sulfasalazine (SSZ), hydroxychloroquine (HCQ) or
methotrexate (MTX). Odds ratios (ORs) for CVD, corrected for age, gender, smoking and RA duration, were calculated per DMARD
group. Patients who never used SSZ, HCQ or MTX were used as a reference group. MTX treatment was associated with a significant
CVD risk reduction, with ORs (95% CI): 'MTX only', 0.16 (0.04 to 0.66); 'MTX and SSZ ever', 0.20 (0.08 to 0.51); and 'MTX,
SSZ and HCQ ever', 0.20 (0.08 to 0.54). The risk reductions remained significant after additional correction for the presence
of rheumatoid factor and erosions. After correction for hypertension, diabetes and hypercholesterolemia, 'MTX or SSZ ever'
and 'MTX, SSZ and HCQ ever' showed significant CVD risk reduction. Rheumatoid factor positivity and erosions both increased
CVD risk, with ORs of 2.04 (1.02 to 4.07) and 2.36 (0.92 to 6.08), respectively. MTX and, to a lesser extent, SSZ were associated
with significantly lower CVD risk compared to RA patients who never used SSZ, HCQ or MTX. We hypothesize that DMARD use, in
particular MTX use, results in powerful suppression of inflammation, thereby reducing the development of atherosclerosis and
subsequently clinically overt CVD. 相似文献
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Maria C Lebre Christina L Jonckheere Maarten C Kraan Arno WR van Kuijk Jan D Bos Menno de Rie Danielle M Gerlag Paul P Tak 《Arthritis research & therapy》2012,14(5):R200