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排序方式: 共有925条查询结果,搜索用时 15 毫秒
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Janette B Gomos Theresa M Rowe Saumendra N Sarkar Sean P Kessler Ganes C Sen 《Journal of interferon & cytokine research》2002,22(2):199-206
The 9-2 isozyme of 2-5 (A) synthetase has cellular proapoptotic functions that are mediated not by enzyme activity but by the Bcl-2 homology domain 3 present in its unique carboxyl-terminal region. Another proapoptotic cellular protein is Bax, whose absence in the Bax(-/-) mice causes male sterility due to abnormal sperm differentiation. In this study, we examined whether transgenic 9-2 expression can substitute for the in vivo reproductive function of Bax. To achieve this goal, a sperm-specific promoter was used to drive the expression of 9-2 in the sperm of transgenic mice. By selective cross-breeding, the transgene was transferred to Bax(-/-) mice to generate the experimental mouse line (Bax(-/-), 9-2(+/+)). The male experimental mice were sterile, and their testes maintained the structural abnormality found in Bax(-/-) mice. Thus, the male reproduction functions of Bax could not be replaced by the 9-2 isozyme of 2-5 (A) synthetase. 相似文献
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Childhood physical and sexual abuse and subsequent depressive and anxiety disorders for two American Indian tribes 总被引:1,自引:0,他引:1
Libby AM Orton HD Novins DK Beals J Manson SM;AI-SUPERPFP Team 《Psychological medicine》2005,35(3):329-340
BACKGROUND: This study examined the relationship of childhood abuse, both physical and sexual, with subsequent lifetime depressive and anxiety disorders--depression or dysthymia, post-traumatic stress disorder (PTSD), and panic or generalized anxiety disorder (GAD)--among American Indians (AIs). METHOD: Three thousand and eighty-four AIs from two tribes--Southwest and Northern Plains--participated in a large-scale, community-based study. Participants were asked about traumatic events and family history, and were administered standard diagnostic measures of depressive/anxiety disorders. RESULTS: Prevalence of childhood physical abuse was approximately 7% for both tribes. The Southwest tribe had higher prevalence of depressive and anxiety disorders, with rates of PTSD being the highest. Childhood physical abuse was significant in bivariate models of depressive/anxiety disorders, and remained so in the multivariate models. CONCLUSIONS: Childhood physical abuse was a significant predictor of all disorder groups for males in both tribes except for panic/GAD for the Northern Plains tribe in multivariate models; females showed a more varied pattern. Childhood sexual abuse did not significantly differ for males and females, and was an independent predictor of PTSD for both tribes, controlling for childhood physical abuse and other factors, and was significant for the other disorder groups only in the Southwest. Additional covariates that increased the odds of depressive/anxiety disorder, were adult physical or sexual victimization, chronic illness, lifetime alcohol or drug disorder, and parental problems with depression, alcohol, or violence. Results provided empirical evidence of childhood and later life risk factors and expanded the population at risk to include males. 相似文献
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Valter Poltojainen Janette Kemppainen Nina Keinnen Michaela Bode JuhaMatti Isokangas Hanne Kuitunen Juha Nikkinen Eila Sonkajrvi Vesa Korhonen Timo Tuovinen Matti Jrvel Niko Huotari Lauri Raitamaa Janne Kananen Tommi Korhonen Sami Tetri Outi Kuittinen Vesa Kiviniemi 《Human brain mapping》2022,43(13):4030
Primary central nervous system lymphoma (PCNSL) is an aggressive brain disease where lymphocytes invade along perivascular spaces of arteries and veins. The invasion markedly changes (peri)vascular structures but its effect on physiological brain pulsations has not been previously studied. Using physiological magnetic resonance encephalography (MREGBOLD) scanning, this study aims to quantify the extent to which (peri)vascular PCNSL involvement alters the stability of physiological brain pulsations mediated by cerebral vasculature. Clinical implications and relevance were explored. In this study, 21 PCNSL patients (median 67y; 38% females) and 30 healthy age‐matched controls (median 63y; 73% females) were scanned for MREGBOLD signal during 2018–2021. Motion effects were removed. Voxel‐by‐voxel Coefficient of Variation (CV) maps of MREGBOLD signal was calculated to examine the stability of physiological brain pulsations. Group‐level differences in CV were examined using nonparametric covariate‐adjusted tests. Subject‐level CV alterations were examined against control population Z‐score maps wherein clusters of increased CV values were detected. Spatial distributions of clusters and findings from routine clinical neuroimaging were compared [contrast‐enhanced, diffusion‐weighted, fluid‐attenuated inversion recovery (FLAIR) data]. Whole‐brain mean CV was linked to short‐term mortality with 100% sensitivity and 100% specificity, as all deceased patients revealed higher values (n = 5, median 0.055) than surviving patients (n = 16, median 0.028) (p < .0001). After adjusting for medication, head motion, and age, patients revealed higher CV values (group median 0.035) than healthy controls (group median 0.024) around arterial territories (p ≤ .001). Abnormal clusters (median 1.10 × 105mm3) extended spatially beyond FLAIR lesions (median 0.62 × 105mm3) with differences in volumes (p = .0055). 相似文献
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The final common pathway to death in all of us is an arrhythmia, yet we still know far too little about the contribution of conduction abnormalities and arrhythmias to the compromised states of the human fetus. At no other time in the human life cycle is the human being at more risk of unexplained and unexpected death than during the prenatal period. The risk of sudden death from 20-40 weeks gestation is 6-12 deaths/1000 fetuses/year. This is equal to, and in some ethnic groups HIGHER than, the risk of death in the adult population with known coronary artery disease over the same time frame (6-12 deaths/1000 patients/year). Because only a small percentage of the United States population is pregnant each year, because fetal demise is not often acknowledged through public displays such as funerals, and finally because fetal death is culturally accepted to a much greater extent than it should be, this critically important area of women's healthcare has not had the technological advances that have been seen in adult cardiac intensive care and other areas of medicine. Fetal cardiac deaths may be preventable and the diseases that lead to these deaths are often treatable, especially if the sophistication of our modern ICU's could somehow be translated to the prenatal monitoring arena. This review article will outline recent advances in evaluating fetal electrophysiology, helping the perinatologist to better understand the nuances of fetal arrhythmias. 相似文献
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Jeanine Jochems Janette Boulden Bridgin G Lee Julie A Blendy Matthew Jarpe Ralph Mazitschek John H Van Duzer Simon Jones Olivier Berton 《Neuropsychopharmacology》2014,39(2):389-400
HDAC inhibitors have been reported to produce antidepressant and pro-cognitive effects in animal models, however, poor brain bioavailability or lack of isoform selectivity of current probes has limited our understanding of their mode of action. We report the characterization of novel pyrimidine hydroxyl amide small molecule inhibitors of HDAC6, brain bioavailable upon systemic administration. We show that two compounds in this family, ACY-738 and ACY-775, inhibit HDAC6 with low nanomolar potency and a selectivity of 60- to 1500-fold over class I HDACs. In contrast to tubastatin A, a reference HDAC6 inhibitor with similar potency and peripheral activity, but more limited brain bioavailability, ACY-738 and ACY-775 induce dramatic increases in α-tubulin acetylation in brain and stimulate mouse exploratory behaviors in novel, but not familiar environments. Interestingly, despite a lack of detectable effect on histone acetylation, we show that ACY-738 and ACY-775 share the antidepressant-like properties of other HDAC inhibitors, such as SAHA and MS-275, in the tail suspension test and social defeat paradigm. These effects of ACY-738 and ACY-775 are directly attributable to the inhibition of HDAC6 expressed centrally, as they are fully abrogated in mice with a neural-specific loss of function of HDAC6. Furthermore, administered in combination, a behaviorally inactive dose of ACY-738 markedly potentiates the anti-immobility activity of a subactive dose of the selective serotonin reuptake inhibitor citalopram. Our results validate new isoform-selective probes for in vivo pharmacological studies of HDAC6 in the CNS and reinforce the viability of this HDAC isoform as a potential target for antidepressant development. 相似文献