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141.
EA Ratovitski MR Alam RA Quick A McMillan C Bao C Kozlovsky TA Hand RC Johnson RE Mains BA Eipper CJ Lowenstein 《Canadian Metallurgical Quarterly》1999,274(2):993-999
Nitric oxide (NO) acts as a neurotransmitter. However, excess NO produced from neuronal NO synthase (nNOS) or inducible NOS (iNOS) during inflammation of the central nervous system can be neurotoxic, disrupting neurotransmitter and hormone production and killing neurons. A screen of a hippocampal cDNA library showed that a unique region of the iNOS protein interacts with Kalirin, previously identified as an interactor with a secretory granule peptide biosynthetic enzyme. Kalirin associates with iNOS in vitro and in vivo and inhibits iNOS activity by preventing the formation of iNOS homodimers. Expression of exogenous Kalirin in pituitary cells dramatically reduces iNOS inhibition of ACTH secretion. Thus Kalirin may play a neuroprotective role during inflammation of the central nervous system by inhibiting iNOS activity. 相似文献
142.
The muscle bundles of the diaphragm form a curved sheet that extends from the chest wall to the central tendon. Each muscle bundle exerts a force in the direction of its curvature; the magnitude of this force is proportional to the curvature of the bundle. The contribution of this force to transdiaphragmatic pressure is maximal if the direction of bundle curvature is orthogonal to the surface and the curvature is maximal. That is, the contribution of muscle tension to transdiaphragmatic pressure is maximal if the muscle bundles lie along lines that are both geodesics and lines of maximal principal curvature of the surface. A theory of diaphragm shape is developed from the assumption that all muscle bundles have these optimal properties. The class of surfaces that are formed of line elements that are both geodescis and lines of principal curvature is described. This class is restricted. The lines that form the surface must lie in planes, and all lines must have the same shape. In addition, the orientation of the lines is restricted. An example of this class that is similar to the shape of the canine diaphragm is described, and the stress distribution in this example is analyzed. 相似文献
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144.
Environmental estrogens and reproductive health: a discussion of the human and environmental data 总被引:1,自引:0,他引:1
GP Daston JW Gooch WJ Breslin DL Shuey AI Nikiforov TA Fico JW Gorsuch 《Canadian Metallurgical Quarterly》1997,11(4):465-481
Estrogenic activity of certain xenobiotics is an established mechanism of toxicity that can impair reproductive function in adults of either sex, lead to irreversible abnormalities when administered during development, or cause cancer. The concern has been raised that exposure to ambient levels of estrogenic xenobiotics may be having widespread adverse effects on reproductive health of humans and wildlife. The purpose of this review is to evaluate (a) the nature of the evidence supporting this concern, and (b) the adequacy of toxicity screening to detect, and risk assessment procedures to establish safe levels for, agents acting by this mechanism. Observations such as adverse developmental effects after maternal exposure to therapeutic levels of the potent estrogen diethylstilbestrol or male fertility problems after exposure to high levels of the weak estrogen chlordecone clearly demonstrate that estrogenicity is active as a toxic mechanism in humans. High level exposures to estrogenic compounds have also been shown to affect specific wildlife populations. However, there is little direct evidence to indicate that exposures to ambient levels of estrogenic xenobiotics are affecting reproductive health. Reports of historical trends showing decreasing reproductive capacity (e.g., decreased sperm production over the last 50 years) are either inconsistent with other data or have significant methodologic inadequacies that hinder interpretation. More reliable historical trend data show an increase in breast cancer rate, but the most comprehensive epidemiology study to data failed to show an association between exposure to persistent, estrogenic organochlorine compounds and breast cancer. Clearly, more work needs to be done to characterize historical trends in humans and background incidence of abnormalities in wildlife populations, and to test hypotheses about ambient exposure to environmental contaminants and toxic effects, before conclusions can be reached about the extent or possible causes of adverse effects. It is unlikely that current lab animal testing protocols are failing to detect agents with estrogenic activity, as a wide array of estrogen-responsive endpoints are measured in standard testing batteries. Routine testing for aquatic and wildlife toxicity is more limited in this respect, and work should be done to assess the validity of applying mammalian toxicology data for submammalian hazard identification. Current risk assessment methods appear to be valid for estrogenic agents, although the database for evaluating this is limited. In conclusion, estrogenicity is an important mechanism of reproductive and developmental toxicity; however, there is little evidence at this point that low level exposures constitute a human or ecologic health risk. Given the potential consequences of an undetected risk, more research is needed to investigate associations between exposures and effects, both in people and animals, and a number of research questions are identified herein. The lack of evidence demonstrating widespread xenobiotic-induced estrogenic risk suggests that far-reaching policy decisions can await these research findings. 相似文献
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146.
The neurophysiological basis of attention control was studied in infants at the second half-year of life, i.e. in the period when the capability for voluntary control over behavior fundamentally improves. EEG was recorded in 60 infants aed 8-11 months in three experimental conditions: 1) attention to an object in the visual field (externally controlled attention, or the baseline state), 2) anticipation of a person in the peek-a-boo game (internally controlled attention), 3) attention to the reappeared person in the peek-a-boo game (control condition). The spectral analysis of the EEG data revealed a sharp increase in the EEG theta (3.6-6.0 Hz) during internally controlled attention as compared to the baseline and control conditions. The theta1 (3.6-4.8 Hz) increase was maximal in the frontal derivations. The reactivity of the frontal theta1 during internally controlled attention discriminated infants with different abilities to maintain this type of attention. The reactivity of the theta2 (5.2-6.0 Hz) was maximal in the right temporal derivation (T6) and did not depend on stability of the anticipatory attention. The findings point to different functional significance of the theta1 and theta2 rhythms in infants. It is suggested that synchronization of the frontal theta1 rhythm in infants reflects the activity of the anterior attention system which realizes the executive attention control. The ability to maintain anticipatory attention increased with age, whereas the frontal theta1 synchronization decreased and totally disappeared at the age of 11 months. At the age of 8 months there was a positive correlation between the frontal theta1 synchronization and behavioral index of stability of the internally controlled attention. On the contrary, this correlation was negative at the age of 9 and 10 months. It is suggested that the age-dependent dynamics of the relationship between the frontal theta1 reactivity and attention reflects a leap in maturation of the anterior attention system resulting in its more economic and efficient functioning. 相似文献
147.
148.
149.
EF Hoffenberg P Kozlowski TA Salerno R Deslauriers 《Canadian Metallurgical Quarterly》1996,62(1):135-143
Methylguanidine, guanidinoacetic acid and guanidinosuccinic acid are endogenous substances in body tissues. Extremely high levels of these substances are known to be related to the pathogenesis of epilepsy and renal failure such as uremia. In this study it was demonstrated that methylguanidine, guanidinoacetic acid and guanidinosuccinic acid, and arginine generate hydroxyl radicals in aqueous solution. These findings suggest that a high level of guanidino compounds accumulating near or within cells such as neurons (in an epileptogenic focus) or nephrons (in uremic patients) may cause free radical damage leading to these clinical disorders. Arginine may have a similar role in the pathogenesis of hyperarginemia. 相似文献
150.
O Lenz LJ Striker TA Jacot SJ Elliot PD Killen GE Striker 《Canadian Metallurgical Quarterly》1998,9(11):2040-2047
Mesangial sclerosis is a major feature of progressive renal disease. The mesangium contains mesangial cells and is bounded by the peripheral glomerular basement membrane and endothelial cells. Mesangial cells synthesize and degrade extracellular matrix. Whereas both mesangial and endothelial cells synthesize extracellular matrix components, the degradative pathway, well studied in the former, has not been investigated in endothelial cells. This study examines lines of all three glomerular cell types derived from female B6SJLF1/J mice, as well as mRNA levels for collagens alpha1(I), alpha1(IV), alpha3 (IV), alpha5 (IV), and alpha1 (VI), laminin, tenascin, matrix metalloproteinase-2 (MMP-2), and MMP-9. Type I and IV collagen synthesis was confirmed by enzyme-linked immunosorbent assay. MMP-2 and MMP-9 enzyme activity was measured by zymography. It was found that glomerular endothelial cells are a significant source of collagens, laminin, and tenascin. However, they express only low levels of MMP-2 and no detectable MMP-9. Stimulation with exogenous transforming growth factor-beta1 leads to a significant increase in collagen I, tissue inhibitors of metalloproteinase-1, and MMP-9 in conditioned media. These data suggest that glomerular endothelial cells may play an active role in extracellular matrix remodeling in glomerular disease. 相似文献