Shear stress differentially activates extracellular signal-regulated kinase (ERK) and c-Jun NH2-terminal kinase (JNK) by mechanisms involving G alpha i2 and G beta/gamma proteins, respectively, in ...bovine aortic endothelial cells (BAEC). The early events in this signaling mechanism by which G proteins regulate ERK and JNK in response to shear stress have not been defined.
Bailey et al present the case of a pregnant 37-year-old Caucasian woman who developed toxic shock syndrome following minor surgery. She lost her baby, but she survived and was discharged home 12 days ...after admission.
In order to study the effects of different rates of rhythmic auditory stimulation on the phonemic accuracy of speakers who have apraxia of speech, eight apraxic subjects read four equated ...monosyllabic passages under one control and three experimental conditions. In the experimental conditions, rhythmic auditory stimulation provided by a metronome was imposed at each subject's oral reading rate as well as 75% and 125% of this established rate. In the control condition, the subjects read without any accompanying rhythmic stimulation. It was found that the stimulus supplied by an auditory metronome did not significantly improve the phonemic accuracy of these subjects. Articulatory accuracy tended to deteriorate under imposed rhythmic stimulation.
Cutis verticis gyrata (CVG) is a rare disorder; it is characterized by thickening of the scalp which becomes raised to form ridges and furrows resembling the cerebral gyri. We report a case of CVG ...associated with the autosomal dominant insulin resistance syndrome. This syndrome is characterized by obesity, mild mental retardation, delayed puberty, acanthosis nigricans and hyperinsulinaemia. The association of CVG and autosomal dominant insulin resistance has not been previously described.
Since the discovery that at least one form of endothelium derived relaxing factor is nitric oxide (NO), numerous studies have uncovered diverse roles for this free radical in a variety of ...physiological and pathophysiological processes. NO production, a process mediated by a family of enzymes termed NO synthases, has been detected in most cell types. Many of the effects of NO are thought to be mediated through its direct interaction with specific and defined cell signaling pathways. The nature of such interactions are highly dependent on the concentration of NO and cell type. Furthermore, specific NO derived reaction products, such as peroxynitrite, also have the potential to effect cell signal transduction events. As with NO, this can occur through diverse mechanisms and depends on concentration and cell type. It is perhaps not surprising that the reported effects of NO in different disease states are often conflicting. In this brief overview, a framework for placing these apparently disparate properties of NO will be described and will focus on the effects of NO and peroxynitrite on signaling pathways.
Two hundred and forty patients with basal cell carcinomas (BCCs) on the head or neck were studied. Scrapings of the lesions were taken for cytological examination, and a 3-mm punch biopsy was ...performed for histopathological study. The accuracy of diagnosis by each method was compared. Both methods confirmed the clinical diagnosis in 226 cases, and both were negative in 10 cases. Cytopathology gave one false negative result (0.42%), and histopathology gave two false negative results (0.83%). Cytopathology gave one false positive result (0.42%), and histopathology did not produce any false positive results. We conclude that cytological examination of skin scrapings from suspected BCCs is a rapid and reliable method of diagnosis.
Laminar shear stress activates c-Jun NH(2)-terminal kinase (JNK) by the mechanisms involving both nitric oxide (NO) and phosphatidylinositide 3-kinase (PI3K). Because protein kinase B (Akt), a ...downstream effector of PI3K, has been shown to phosphorylate and activate endothelial NO synthase, we hypothesized that Akt regulates shear-dependent activation of JNK by stimulating NO production. Here, we examined the role of Akt in shear-dependent NO production and JNK activation by expressing a dominant negative Akt mutant (Akt(AA)) and a constitutively active mutant (Akt(Myr)) in bovine aortic endothelial cells (BAEC). As expected, pretreatment of BAEC with the PI3K inhibitor (wortmannin) prevented shear-dependent stimulation of Akt and NO production. Transient expression of Akt(AA) in BAEC by using a recombinant adenoviral construct inhibited the shear-dependent stimulation of NO production and JNK activation. However, transient expression of Akt(Myr) by using a recombinant adenoviral construct did not induce JNK activation. This is consistent with our previous finding that NO is required, but not sufficient on its own, to activate JNK in response to shear stress. These results and our previous findings strongly suggest that shear stress triggers activation of PI3K, Akt, and endothelial NO synthase, leading to production of NO, which (along with O(2-), which is also produced by shear) activates Ras-JNK pathway. The regulation of Akt, NO, and JNK by shear stress is likely to play a critical role in its antiatherogenic effects.
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