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Summary— Acidosis affects multiple steps in the excitation-contraction coupling pathway of myocardium, producing decreased calcium sensitivity of myofibrils and modification of the function of the sarcoplasmic reticulum. Our aim was to evaluate the effectiveness of three different classes of inotropic agents under acidotic conditions: 1) forskolin, an adenylate cyclase activator that enhances cellular cyclic AMP concentrations, 2) elevated extracellular Ca2+ and 3) endothelin-1, an activator of the inositol triphosphate, diacylglycerol pathway. Ferret papillary muscles were mounted in organ baths containing normal physiological solution (pH = 7.4). After baseline tension was measured, the muscles were bathed in an acidotic solution (pH = 6.98) that decreased tension to 40% of the control; subsequently, the muscles were washed with normal physiological solution until they returned to baseline. Each inotropic agent was added to the bathing solution in a concentration sufficient to increase tension by 40% above the baseline. Then the solution was made acidotic (pH = 6.98) in the continuous presence of that concentration of inotropic agent and the resultant steady-state developed tension measured. The increases in tension induced by each inotropic agent at normal pH were adjusted to be similar; in contrast, the response to each drug in acidosis was significantly different. Under acidotic conditions, endothelin-1 was the most effective inotropic agent in restoring the depressed developed tension. This was possibly due to enhancement of the myofilament sensitivity to Ca2+ , which was more effective than increasing [Ca2+ ]i through elevating extracellular Ca2+ or the addition of forskolin which increased [Ca2+ ]i but desensitized the myofilaments to Ca2+ . 相似文献
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Shared care: a review of the literature 总被引:7,自引:1,他引:6
This review examines broad issues of concern regarding the primary/secondarycare interface. The main purpose was to identify areas of goodpractice which could be adapted for more general use. One ofthe most fundamental aspects identified was communication, whichis discussed in some detail. Also covered are shared prescribingand disease management. The data suggest that the most effectivesystem(s) of shared care has yet to be established. Furtherqualitative and economic evaluations are required, taking intoaccount patient preferences. Although the literature does describecertain practice exemplars, it is clear that inter- and intra-professionalcommunication continues to be a problem. Whilst informationtechnology may provide some of the solutions, it is concludedthat a culture change, which compels health professionals tomake sharing of patient information a much higher priority,is reauired. Keywords. Shared care, seamless care, hospital, general practice, family practice. 相似文献
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Chaperonin-mediated assembly of wild-type and mutant subunits of human propionyl-CoA carboxylase expressed in Escherichia coli 总被引:1,自引:0,他引:1
We developed a bacterial expression system for the human alpha and beta
cDNAs of propionyl-CoA carboxylase (PCC). These cDNAs (less the putative
mitochondrial matrix targeting presequences) were co-expressed in
Escherichia coli on one plasmid vector with each cDNA having its own
IPTG-inducible promoter. Only negligible amounts of active PCC were
measured despite the presence of both alpha and beta subunits as indicated
by Western blot analysis and the almost complete biotinylation of the alpha
subunit. Co-expression of this plasmid with a second plasmid vector
over-expressing the E. coli chaperonin proteins, groES and groEL, resulted
in a several hundred-fold increase in PCC specific activity, to a level
comparable with that found in crude human liver extracts. PCC was partially
purified on monomeric avidin affinity resin and the presence of both alpha
and beta subunits was demonstrated, thereby confirming the assembly of both
subunits into an active enzyme. Deficiency of either alpha PCC or beta PCC
results in propionic acidemia, an autosomal recessive disorder. We used
this expression system to characterize one missense mutation previously
described in five Japanese alleles, namely C1283T (Thr428lle) in beta PCC.
This mutation, when expressed in E.coli under the same conditions as that
of wild-type PCC, had null activity, despite the presence of assembled
alpha PCC and beta PCC subunits. This bacterial expression system can be
useful for analysis of either alpha PCC or beta PCC mutations. Our findings
indicated that the groES and groEL chaperonin proteins were essential for
folding and assembly of the human PCC heteromeric subunits.
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A novel C202F mutation in the connexin26 gene (GJB2) associated with autosomal dominant isolated hearing loss 下载免费PDF全文
Morlé L Bozon M Alloisio N Latour P Vandenberghe A Plauchu H Collet L Edery P Godet J Lina-Granade G 《Journal of medical genetics》2000,37(5):368-370
Mutations in the GJB2 gene encoding connexin26 (CX26) account for up to 50% of cases of autosomal recessive hearing loss. In contrast, only one GJB2 mutation has been reported to date in an autosomal dominant form of isolated prelingual hearing loss. We report here a novel heterozygous 605G→T mutation in GJB2 in all affected members of a large family with late childhood onset of autosomal dominant isolated hearing loss. The resulting C202F substitution, which lies in the fourth (M4) transmembrane domain of CX26, may impair connexin oligomerisation. Finally, our study suggests that GJB2 should be screened for heterozygous mutations in patients with autosomal dominant isolated hearing impairment, whatever the severity of the disease.
Keywords: C202F mutation; connexin26 gene (GJB2); autosomal dominant hearing loss 相似文献
Keywords: C202F mutation; connexin26 gene (GJB2); autosomal dominant hearing loss 相似文献
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JJ Favre Ph Chaffanjon JG Passagia JP Chirossel 《Surgical and radiologic anatomy : SRA》1995,17(2):133-138
Summary The authors report the results of a series of dissections and anatomic sections of the fronto-basal region of the brain and of the anterior cranial fossa in human cadavers. The constant presence of an arachnoidal cistern above the olfactory nerve was verified. The arachnoid separates from the pial membrane and forms a bridge with the ventral part of the olfactory bulb and tract, from the lateral edge of the olfactory sulcus to the medial edge of the gyrus rectus. The cistern is wide in its anterior portion, between the gyrus rectus and the olfactory bulb, and is reduced to a virtual slit in its posterior portion where the tract is lodged in the olfactory sulcus. The olfactory nerve can be separated without damaging fronto-basal arachnoidial adhesions over several centimeters. Dissection of this region after intravascular injection of colored media shows the constant presence of an artery destined to the olfactory bulb and tract. It originates either from the lateral surface of the anterior cerebral a. (segment A2), or from the medial fronto-basal a., and consistently provides terminal branches in front of the olfactory trigone in the medial olfactory sulcus. At their ventral extremity, the olfactory structures are therefore vascularised independently for several centimeters, from the lower face of the frontal lobe. The independent vascularisation of the olfactory nerve, the tenuous and easily detachable adhesions, and the actual presence of a true arachnoidal cistern all contribute to enabling surgical techniques which conserve olfactory function during anterior approaches.
Vascularisation du nerf olfactif. Rapports méningés et applications chirurgicales
Résumé Les auteurs rapportent les résultats d'une série de dissections et de coupes de la région fronto-basale de l'encéphale et de la fosse crânienne antérieure sur sujets cadavériques. La présence constante d'une citerne arachnoïdienne au dessus du n. olfactif a été vérifiée. L'arachnoïde se sépare du feuillet pial et passe en pont à la partie ventrale du bulbe et du tractus olfactifs, du bord latéral du sillon olfactif au bord médial du gyrus rectus. La citerne est large dans sa portion antérieure, entre le gyrus rectus et le bulbe olfactif, se réduit à une fente virtuelle postérieure lorsque le tractus se loge dans le sillon olfactif. Le n. olfactif peut être séparé sans dommage des adhérences arachnoïdiennes fronto-basales sur quelques centimètres. La dissection de cette région, après injection intravasculaire de masses colorées montre, de façon originale, la présence constante d'une artère destinée au tractus et au bulbe olfactifs. Elle naît soit de la face latérale de l'a. cérébrale antérieure (segment A2), soit de l'a. fronto-basale médiale, pour donner ses branches terminales toujours en avant du trigone olfactif dans le sillon orbitaire médial. Sur quelques centimètres à leur extrémité ventrale, les structures olfactives ont donc une vascularisation indépendante de la face inférieure du lobe frontal. L'indépendance vasculaire du n. olfactif, des adhérences ténues, facilement détachables, et la réalité vérifiée d'une véritable citerne arachnoïdienne permettent d'imaginer des techniques conservatrices de la fonction olfactive utilisées dans plusieurs indications de la chirurgie de la fosse crânienne antérieure.相似文献