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Articles 12661 - 12690 of 15660
Full-Text Articles in Entire DC Network
Maternal Magnesium Deficiency In Mice Leads To Maternal Metabolic Dysfunction And Altered Lipid Metabolism With Fetal Growth Restriction, M. Gupta, M. H. Solanki, P. K. Chatterjee, X. Y. Xue, A. Roman, N. Desai, B. Rochelson, C. N. Metz
Maternal Magnesium Deficiency In Mice Leads To Maternal Metabolic Dysfunction And Altered Lipid Metabolism With Fetal Growth Restriction, M. Gupta, M. H. Solanki, P. K. Chatterjee, X. Y. Xue, A. Roman, N. Desai, B. Rochelson, C. N. Metz
Journal Articles
Inadequate magnesium (Mg) intake is a widespread problem, with over 50% of women of reproductive age consuming less than the Recommended Dietary Allowance (RDA). Because pregnancy increases the requirement for Mg and the beneficial effects of magnesium sulfate for preeclampsia/eclampsia and fetal neuroprotection are well described, we examined the outcomes of Mg deficiency during pregnancy. Briefly, pregnant Swiss Webster mice were fed either control or Mg-deficient diets starting on gestational day (GD) 6 through euthanasia on GD17. Mg-deficient dams had significantly reduced weight gain and higher plasma adipokines, in the absence of inflammation. Livers of Mg-deficient dams had significantly higher …
Regional Brain Metabolism In A Murine Systemic Lupus Erythematosus Model, An Vo, B. T. Volpe, C. C. Tang, W. K. Schiffer, C. Kowal, P. T. Huerta, A. M. Ulug, S. L. Dewey, D. Eidelberg, B. Diamond
Regional Brain Metabolism In A Murine Systemic Lupus Erythematosus Model, An Vo, B. T. Volpe, C. C. Tang, W. K. Schiffer, C. Kowal, P. T. Huerta, A. M. Ulug, S. L. Dewey, D. Eidelberg, B. Diamond
Journal Articles
Systemic lupus erythematosus (SLE) is characterized by multiorgan inflammation, neuropsychiatric disorders (NPSLE), and antinuclear antibodies. We previously identified a subset of anti-DNA antibodies (DNRAb) cross-reactive with the N-methyl-D-aspartate receptor, present in 30% to 40% of patients, able to enhance excitatory post-synaptic potentials and trigger neuronal apoptosis. DNRAb + mice exhibit memory impairment or altered fear response, depending on whether the antibody penetrates the hippocampus or amygdala. Here, we used 18F-fluorodeoxyglucose (FDG) microPET to plot changes in brain metabolism after regional blood-brain barrier (BBB) breach. In DNRAb + mice, metabolism declined at the site of BBB breach in the first 2 …
Brain Region-Specific Alterations In The Gene Expression Of Cytokines, Immune Cell Markers And Cholinergic System Components During Peripheral Endotoxin-Induced Inflammation, H. A. Silverman, M. Dancho, A. Regnier-Golanov, M. Nasim, M. Ochani, P. S. Olofsson, M. Ahmed, E. J. Miller, S. S. Chavan, E. Golanov, C. Metz, K. J. Tracey, V. A. Pavlov
Brain Region-Specific Alterations In The Gene Expression Of Cytokines, Immune Cell Markers And Cholinergic System Components During Peripheral Endotoxin-Induced Inflammation, H. A. Silverman, M. Dancho, A. Regnier-Golanov, M. Nasim, M. Ochani, P. S. Olofsson, M. Ahmed, E. J. Miller, S. S. Chavan, E. Golanov, C. Metz, K. J. Tracey, V. A. Pavlov
Journal Articles
Inflammatory conditions characterized by excessive peripheral immune responses are associated with diverse alterations in brain function, and brain-derived neural pathways regulate peripheral inflammation. Important aspects of this bidirectional peripheral immune - brain communication, including the impact of peripheral inflammation on brain region-specific cytokine responses, and brain cholinergic signaling (which plays a role in controlling peripheral cytokine levels) remain unclear. To provide insight, we studied gene expression of cytokines, immune cell markers and brain cholinergic system components in the cortex, cerebellum, brainstem, hippocampus, hypothalamus, striatum, and thalamus in mice following an intraperitoneal lipopolysaccharide injection. Endotoxemia was accompanied by elevated serum levels …
Laser-Assisted Zona Pellucida Thinning Does Not Facilitate Hatching And May Disrupt The In Vitro Hatching Process: A Morphokinetic Study In The Mouse, T. Schimmel, J. Cohen, H. Saunders, M. Alikani
Laser-Assisted Zona Pellucida Thinning Does Not Facilitate Hatching And May Disrupt The In Vitro Hatching Process: A Morphokinetic Study In The Mouse, T. Schimmel, J. Cohen, H. Saunders, M. Alikani
Journal Articles
STUDY QUESTION: Does laser-assisted zona thinning of cleavage stage mouse embryos facilitate hatching in vitro? SUMMARY ANSWER: No, unlike laser zona opening, zona thinning does not facilitate embryo hatching. WHAT IS KNOWN ALREADY: Artificial opening of the zona pellucida facilitates hatching of mouse and human embryos. Laser-assisted zona thinning has also been used for the purpose of assisted hatching of human embryos but it has not been properly investigated in an animal model; thinning methods have produced inconsistent clinical results. STUDY DESIGN, SIZE, DURATION: Time-lapse microscopy was used to study the hatching process in the mouse after zona opening and …
Intracellular Hmgb1 Inhibits Inflammatory Nucleosome Release And Limits Acute Pancreatitis In Mice, R. Kang, Q. Zhang, W. Hou, Z. Yan, R. Chen, J. Bonaroti, P. Bansal, T. R. Billiar, A. Tsung, Q. Wang, D. L. Bartlett, D. C. Whitcomb, E. B. Chang, X. Zhu, H. Wang, B. Lu, K. J. Tracey, L. Cao, X. G. Fan, M. T. Lotze, H. J., 3rd Zeh, D. Tang
Intracellular Hmgb1 Inhibits Inflammatory Nucleosome Release And Limits Acute Pancreatitis In Mice, R. Kang, Q. Zhang, W. Hou, Z. Yan, R. Chen, J. Bonaroti, P. Bansal, T. R. Billiar, A. Tsung, Q. Wang, D. L. Bartlett, D. C. Whitcomb, E. B. Chang, X. Zhu, H. Wang, B. Lu, K. J. Tracey, L. Cao, X. G. Fan, M. T. Lotze, H. J., 3rd Zeh, D. Tang
Journal Articles
BACKGROUND & AIMS: High mobility group box 1 (HMGB1) is an abundant protein that regulates chromosome architecture and also functions as a damage-associated molecular pattern molecule. Little is known about its intracellular roles in response to tissue injury or during subsequent local and systemic inflammatory responses. We investigated the function of Hmgb1 in mice after induction of acute pancreatitis. METHODS: We utilized a Cre/LoxP system to create mice with pancreas-specific disruption in Hmbg1 (Pdx1-Cre; HMGB1(flox/flox) mice). Acute pancreatitis was induced in these mice (HMGB1(flox/flox) mice served as controls) after injection of l-arginine or cerulein. Pancreatic tissues and acinar cells were …
Hmgb1-Dna Complex-Induced Autophagy Limits Aim2 Inflammasome Activation Through Rage, L. Y. Liu, M. H. Yang, R. Kang, Y. P. Dai, X. J. Sun, X. L. Li, J. H. Li, H. C. Wang, L. Z. Cao, D. L. Tang, +3 Additional Authors
Hmgb1-Dna Complex-Induced Autophagy Limits Aim2 Inflammasome Activation Through Rage, L. Y. Liu, M. H. Yang, R. Kang, Y. P. Dai, X. J. Sun, X. L. Li, J. H. Li, H. C. Wang, L. Z. Cao, D. L. Tang, +3 Additional Authors
Journal Articles
High mobility group box 1 (HMGB1) is a prototype damage-associated molecular pattern (DAMP) that can induce inflammatory and immune responses alone as well as in combination with other molecules such as DNA. However, the intricate molecular mechanisms underlying HMGB1-DNA complex-mediated innate immune response remains largely elusive. In this study, we demonstrated that HMGB1-DNA complex initially induced absent in melanoma 2 (AIM2)-dependent inflammasome activation, and promoted rapid release of inflammasome-dependent early proinflammatory cytokines such as interleukin 10 (IL-1 beta). Subsequently, HMGB1 - DNA complex stimulated an ATG5-dependent cellular degradation process, autophagy, which was paralleled by a cessation of AIM2 inflammasome activation …
Molecular Mechanism And Therapeutic Modulation Of High Mobility Group Box 1 Release And Action: An Updated Review, B. Lu, C. Wang, M. Wang, W. Li, F. P. Chen, K. J. Tracey, H. C. Wang
Molecular Mechanism And Therapeutic Modulation Of High Mobility Group Box 1 Release And Action: An Updated Review, B. Lu, C. Wang, M. Wang, W. Li, F. P. Chen, K. J. Tracey, H. C. Wang
Journal Articles
High mobility group box 1 (HMGB1) is an evolutionarily conserved protein, and is constitutively expressed in virtually all types of cells. Infection and injury converge on common inflammatory responses that are mediated by HMGB1 secreted from immunologically activated immune cells or passively released from pathologically damaged cells. Herein we review the emerging molecular mechanisms underlying the regulation of pathogen-associated molecular patterns (PAMPs)-induced HMGB1 secretion, and summarize many HMGB1-targeting therapeutic strategies for the treatment of infection- and injury-elicited inflammatory diseases. It may well be possible to develop strategies that specifically attenuate damage-associated molecular patterns (DAMPs)-mediated inflammatory responses without compromising the PAMPs-mediated …
Gene-Based Therapies In Parkinson's Disease, P. J. Allen, A. Feigin
Gene-Based Therapies In Parkinson's Disease, P. J. Allen, A. Feigin
Journal Articles
Parkinson's disease (PD) is a progressive neurological disorder characterized primarily by the degeneration of nigrostriatal dopaminergic neurons and diminution of the neurotransmitter dopamine. Though dopamine replacement therapies such as levodopa can improve the symptoms of PD, the benefits may be overshadowed by side effects and the onset of symptoms not responsive to dopaminergic treatments (e.g., autonomic symptoms, gait and balance problems, and cognitive impairment). Furthermore, no therapies have proven to slow the neurodegenerative process. Novel approaches to address these difficult problems, and others, are being sought. Over the last decade, several innovative gene therapies for PD have entered human clinical …
Sex Differences In Anxiety And Depression Clinical Perspectives, M. Altemus, N. Sarvaiya, C. N. Epperson
Sex Differences In Anxiety And Depression Clinical Perspectives, M. Altemus, N. Sarvaiya, C. N. Epperson
Journal Articles
Sex differences are prominent in mood and anxiety disorders and may provide a window into mechanisms of onset and maintenance of affective disturbances in both men and women. With the plethora of sex differences in brain structure, function, and stress responsivity, as well as differences in exposure to reproductive hormones, social expectations and experiences, the challenge is to understand which sex differences are relevant to affective illness. This review will focus on clinical aspects of sex differences in affective disorders including the emergence of sex differences across developmental stages and the impact of reproductive events. Biological, cultural, and experiential factors …
Dopaminergic Influences On Emotional Decision Making In Euthymic Bipolar Patients, K. E. Burdick, R. J. Braga, C. B. Gopin, A. K. Malhotra
Dopaminergic Influences On Emotional Decision Making In Euthymic Bipolar Patients, K. E. Burdick, R. J. Braga, C. B. Gopin, A. K. Malhotra
Journal Articles
We recently reported that the D2/D3 agonist pramipexole may have pro-cognitive effects in euthymic patients with bipolar disorder (BPD); however, the emergence of impulse-control disorders has been documented in Parkinson's disease (PD) after pramipexole treatment. Performance on reward-based tasks is altered in healthy subjects after a single dose of pramipexole, but its potential to induce abnormalities in BPD patients is unknown. We assessed reward-dependent decision making in euthymic BPD patients pre- and post 8 weeks of treatment with pramipexole or placebo by using the Iowa Gambling Task (IGT). The IGT requires subjects to choose among four card decks (two risky …
Apoe Genotype Modulates Proton Magnetic Resonance Spectroscopy Metabolites In The Aging Brain, J. J. Gomar, M. L. Gordon, P. B. Kingsley, A. M. Ulug, L. Keehlisen, S. Huet, J. J. Buthorn, J. Koppel, E. Christen, C. Conejero-Goldberg, P. Davies, T. E. Goldberg, +1 Additional Author
Apoe Genotype Modulates Proton Magnetic Resonance Spectroscopy Metabolites In The Aging Brain, J. J. Gomar, M. L. Gordon, P. B. Kingsley, A. M. Ulug, L. Keehlisen, S. Huet, J. J. Buthorn, J. Koppel, E. Christen, C. Conejero-Goldberg, P. Davies, T. E. Goldberg, +1 Additional Author
Journal Articles
Background: Proton magnetic resonance spectroscopy (H-1-MRS) studies on healthy aging have reported inconsistent findings and have not systematically taken into account the possible modulatory effect of APOE genotype. We aimed to quantify brain metabolite changes in healthy subjects in relation to age and the presence of the APOE E4 genetic risk factor for Alzheimer's disease. Additionally, we examined these measures in relation to cognition. Methods: We studied a cohort of 112 normal adults between 50 and 86 years old who were genotyped for APOE genetic polymorphism. Measurements of H-1-MRS metabolites were obtained in the posterior cingulate and precuneus region. Measures …
Cb2 Receptor Deficiency Increases Amyloid Pathology And Alters Tau Processing In A Transgenic Mouse Model Of Alzheimer's Disease, Jeremy Koppel, V. Vingtdeux, P. Marambaud, C. D'Abramo, H. Jimenez, M. Stauber, R. Friedman, P. Davies
Cb2 Receptor Deficiency Increases Amyloid Pathology And Alters Tau Processing In A Transgenic Mouse Model Of Alzheimer's Disease, Jeremy Koppel, V. Vingtdeux, P. Marambaud, C. D'Abramo, H. Jimenez, M. Stauber, R. Friedman, P. Davies
Journal Articles
The endocannabinoid CB2 receptor system has been implicated in the neuropathology of Alzheimer's disease (AD). In order to investigate the impact of the CB2 receptor system on AD pathology, a colony of mice with a deleted CB2 receptor gene, CNR2, was established on a transgenic human mutant APP background for pathological comparison with CB2 receptor-sufficient transgenic mice. J20 APP (PDGFB-APPSwInd) mice were bred over two generations with CNR2(-/-) (Cnr2(tm1Dgen)/J) mice to produce a colony of J20 CNR2(+/+) and J20 CNR2(-/-)mice. Seventeen J20 CNR2(+/+) mice (12 females, 5 males) and 16 J20 CNR2(-/-) mice (11 females, 5 males) were killed at …
Alpha 7 Nicotinic Acetylcholine Receptor Signaling Inhibits Inflammasome Activation By Preventing Mitochondrial Dna Release, B. Lu, K. Kwan, Y. A. Levine, P. S. Olofsson, H. Yang, J. H. Li, S. Joshi, H. C. Wang, U. Andersson, S. S. Chavan, K. J. Tracey
Alpha 7 Nicotinic Acetylcholine Receptor Signaling Inhibits Inflammasome Activation By Preventing Mitochondrial Dna Release, B. Lu, K. Kwan, Y. A. Levine, P. S. Olofsson, H. Yang, J. H. Li, S. Joshi, H. C. Wang, U. Andersson, S. S. Chavan, K. J. Tracey
Journal Articles
The mammalian immune system and the nervous system coevolved under the influence of cellular and environmental stress. Cellular stress is associated with changes in immunity and activation of the NACHT, LRR and PYD domains-containing protein 3 (NLRP3) inflammasome, a key component of innate immunity. Here we show that alpha 7 nicotinic acetylcholine receptor (alpha 7 nAchR)-signaling inhibits inflammasome activation and prevents release of mitochondrial DNA, an NLRP3 ligand. Cholinergic receptor agonists or vagus nerve stimulation significantly inhibits inflammasome activation, whereas genetic deletion of alpha 7 nAchR significantly enhances inflammasome activation. Acetylcholine accumulates in macrophage cytoplasm after adenosine triphosphate (ATP) stimulation …
The Content Of Attenuated Psychotic Symptoms In Those At Clinical High Risk For Psychosis, C. Marshall, E. Denny, K. S. Cadenhead, T. D. Cannon, Barbara Cornblatt, T. H. Mcglashan, D. O. Perkins, L. J. Seidman, M. T. Tsuang, J. Addington, +2 Additional Authors
The Content Of Attenuated Psychotic Symptoms In Those At Clinical High Risk For Psychosis, C. Marshall, E. Denny, K. S. Cadenhead, T. D. Cannon, Barbara Cornblatt, T. H. Mcglashan, D. O. Perkins, L. J. Seidman, M. T. Tsuang, J. Addington, +2 Additional Authors
Journal Articles
Recent research has started to focus on identifying individuals who are at clinical high risk of developing psychosis as a means to try and understand the predictors and mechanisms involved in the progress to a full psychotic episode. The aim of the current study was to provide an initial description and prevalence rates of specific content found within attenuated positive symptoms. The Content of Attenuated Positive Symptoms (CAPS) codebook was used by independent raters to determine the presence of content within a sample of written vignettes. Krippendorff's alpha was used to determine inter-rater reliability. Overall, the majority of items fell …
Bdnf Val66met Polymorphism And Antipsychotic-Induced Tardive Dyskinesia Occurrence And Severity: A Meta-Analysis, I. Miura, Jianping Zhang, M. Nitta, T. Lencz, John Kane, Anil Malhotra, H. Yabe, Christoph Correll
Bdnf Val66met Polymorphism And Antipsychotic-Induced Tardive Dyskinesia Occurrence And Severity: A Meta-Analysis, I. Miura, Jianping Zhang, M. Nitta, T. Lencz, John Kane, Anil Malhotra, H. Yabe, Christoph Correll
Journal Articles
Background: Tardive dyskinesia (TD) is a serious long-term consequence of antipsychotic treatment. Since brain-derived neurotrophic factor (BDNF) has potent neurotrophic activity, genetic alterations in the BDNF gene may affect antipsychotic-induced TD. Methods: Searching PubMed and Web of Science until 05/31/13, we conducted a systematic review and a meta-analysis of the effects of BDNF Val66Met polymorphism on antipsychotic-induced TD. Pooled odds ratio was calculated to assess the effects of BDNF Val66Met polymorphism on TD occurrence. Additionally, pooled standardized mean differences (Hedges'g) were calculated to assess the effects on Abnormal Involuntary Movement Scale (AIMS) total score. Results: Out of 699 potentially eligible …
Matrics Cognitive Consensus Battery (Mccb) Performance In Children, Adolescents, And Young Adults, G. C. Nitzburg, P. Derosse, K. E. Burdick, B. D. Peters, C. B. Gopin, Anil Malhotra
Matrics Cognitive Consensus Battery (Mccb) Performance In Children, Adolescents, And Young Adults, G. C. Nitzburg, P. Derosse, K. E. Burdick, B. D. Peters, C. B. Gopin, Anil Malhotra
Journal Articles
Background: Neurodevelopmental models of schizophrenia suggest that cognitive deficits may be observed during childhood and adolescence, long before the onset of psychotic symptoms. Elucidating the trajectory of normal cognitive development during childhood and adolescence may therefore provide a basis for identifying specific abnormalities related to the development of schizophrenia. The MATRICS Consensus Cognitive Battery (MCCB), which was designed for use in clinical trials targeting cognitive deficits most common in schizophrenia, may provide a mechanism to understand this trajectory. To date, however, there is no performance data for the MCCB in healthy children and adolescents. The present study sought to establish …
Age-Related Differences In White Matter Tract Microstructure Are Associated With Cognitive Performance From Childhood To Adulthood, B. D. Peters, T. Ikuta, P. Derosse, M. John, K. E. Burdick, P. Gruner, D. M. Prendergast, Philip Szeszko, Anil Malhotra
Age-Related Differences In White Matter Tract Microstructure Are Associated With Cognitive Performance From Childhood To Adulthood, B. D. Peters, T. Ikuta, P. Derosse, M. John, K. E. Burdick, P. Gruner, D. M. Prendergast, Philip Szeszko, Anil Malhotra
Journal Articles
Background: Age-related differences in white matter tract microstructure have been well established across the life span. In the present cross-sectional study, we examined whether these differences are associated with neurocognitive performance from childhood to late adulthood. Methods: Diffusion tensor imaging was performed in 296 healthy subjects aged 8 to 68 years (mean = 29.6, SD = 14.6). The corpus callosum, two projection tracts, and five association tracts were traced using probabilistic tractography. A neurocognitive test battery was used to assess speed of processing, attention, spatial working memory, verbal functioning, visual learning, and executive functioning. Linear mediation models were used to …
Brain White Matter Development Is Associated With A Human-Specific Haplotype Increasing The Synthesis Of Long Chain Fatty Acids, B. D. Peters, A. N. Voineskos, P. R. Szeszko, T. A. Lett, P. Derosse, S. Guha, K. H. Karlsgodt, M. John, T. Lencz, A. K. Malhotra, +4 Additional Authors
Brain White Matter Development Is Associated With A Human-Specific Haplotype Increasing The Synthesis Of Long Chain Fatty Acids, B. D. Peters, A. N. Voineskos, P. R. Szeszko, T. A. Lett, P. Derosse, S. Guha, K. H. Karlsgodt, M. John, T. Lencz, A. K. Malhotra, +4 Additional Authors
Journal Articles
The genetic and molecular pathways driving human brain white matter (WM) development are only beginning to be discovered. Long chain polyunsaturated fatty acids (LC-PUFAs) have been implicated in myelination in animal models and humans. The biosynthesis of LC-PUFAs is regulated by the fatty acid desaturase (FADS) genes, of which a human-specific haplotype is strongly associated with omega-3 and omega-6 LC-PUFA concentrations in blood. To investigate the relationship between LC-PUFA synthesis and human brain WM development, we examined whether this FADS haplotype is associated with age-related WM differences across the life span in healthy individuals 9-86 years of age (n = …
Delineation Of Hippocampal Subregions Using T1-Weighted Magnetic Resonance Images At 3 Tesla, K. Rhindress, T. Ikuta, R. Wellington, A. K. Malhotra, P. Szeszko
Delineation Of Hippocampal Subregions Using T1-Weighted Magnetic Resonance Images At 3 Tesla, K. Rhindress, T. Ikuta, R. Wellington, A. K. Malhotra, P. Szeszko
Journal Articles
Although several novel approaches for hippocampal subregion delineation have been developed, they need to be applied prospectively and may be limited by long scan times, the use of high field (>3T) imaging systems, and limited reliability metrics. Moreover, the majority of MR imaging data collected to date has employed a T1-weighted acquisition, creating a critical need for an approach that provides reliable hippocampal subregion segmentation using such a contrast. We present a highly reliable approach for the identification of six subregions comprising the hippocampal formation from MR images including the subiculum, dentate gyrus/cornu Ammonis 4 (DG/CA4), entorhinal cortex, fimbria, …
White Matter Changes Associated With Antipsychotic Treatment In First-Episode Psychosis, P. Szeszko, D. G. Robinson, T. Ikuta, B. D. Peters, J. Gallego, J. Kane, A. K. Malhotra
White Matter Changes Associated With Antipsychotic Treatment In First-Episode Psychosis, P. Szeszko, D. G. Robinson, T. Ikuta, B. D. Peters, J. Gallego, J. Kane, A. K. Malhotra
Journal Articles
Second-generation antipsychotics are utilized extensively in the treatment of psychotic disorders and other psychiatric conditions, but the effects of these medications on human brain white matter are not well understood. We thus investigated the effects of second-generation antipsychotics on white matter integrity using tract-based spatial statistics in patients experiencing a first episode of psychosis with little or no prior antipsychotic exposure, and how potential changes were associated with metabolic side effects. Thirty-five (26 men/9 women) patients experiencing a first episode of psychosis received diffusion tensor imaging (DTI) exams, clinical assessments, and provided fasting blood samples at the onset of antipsychotic …
Expression Of Blimp-1 In Dendritic Cells Modulates The Innate Inflammatory Response In Dextran Sodium Sulfate-Induced Colitis, S. J. Kim, J. Goldstein, K. Dorso, M. Merad, L. Mayer, J. M. Crawford, P. K. Gregersen, B. Diamond
Expression Of Blimp-1 In Dendritic Cells Modulates The Innate Inflammatory Response In Dextran Sodium Sulfate-Induced Colitis, S. J. Kim, J. Goldstein, K. Dorso, M. Merad, L. Mayer, J. M. Crawford, P. K. Gregersen, B. Diamond
Journal Articles
A single nucleotide polymorphism of PRDM1, the gene encoding Blimp-1, is strongly associated with inflammatory bowel disease. Here, we demonstrate that Blimp-1 in CD103(+) dendritic cells (DCs) critically contributes to the regulation of macrophage homeostasis in the colon. Dextran sodium sulfate (DSS)-exposed Blimp-1(cko) mice with a deletion of Blimp-1 in CD103(+) DCs and CD11c(hi) macrophages exhibited severe inflammatory symptoms, pronounced weight loss, high mortality, robust infiltration of neutrophils in epithelial regions of the colon, an increased expression of proinflammatory cytokines and a significant decrease in CD103(+) DCs in the colon compared with DSS exposed wild-type (WT) mice. Purified colonic macrophages …
Inhibition Of Extracellular Hmgb1 Attenuates Hyperoxia-Induced Inflammatory Acute Lung Injury, M. Entezari, M. Javdan, D. J. Antoine, D. M. Morrow, R. A. Sitapara, V. Patel, M. Wang, L. Sharma, H. Wang, L. L. Mantell, +7 Additional Authors
Inhibition Of Extracellular Hmgb1 Attenuates Hyperoxia-Induced Inflammatory Acute Lung Injury, M. Entezari, M. Javdan, D. J. Antoine, D. M. Morrow, R. A. Sitapara, V. Patel, M. Wang, L. Sharma, H. Wang, L. L. Mantell, +7 Additional Authors
Journal Articles
Prolonged exposure to hyperoxia results in acute lung injury (ALI), accompanied by a significant elevation in the levels of proinflammatory cytokines and leukocyte infiltration in the lungs. However, the mechanisms underlying hyperoxia-induced proinflammatory ALI remain to be elucidated. In this study, we investigated the role of the proinflammatory cytokine high mobility group box protein 1 (HMGB1) in hyperoxic inflammatory lung injury, using an adult mouse model. The exposure of C57BL/6 mice to >/=99% O2 (hyperoxia) significantly increased the accumulation of HMGB1 in the bronchoalveolar lavage fluids (BALF) prior to the onset of severe inflammatory lung injury. In the airways of …
Mitochondrial Dna Copy Numbers In Pyramidal Neurons Are Decreased And Mitochondrial Biogenesis Transcriptome Signaling Is Disrupted In Alzheimer’S Disease Hippocampi, Ann C. Rice, Paula M. Keeney, Norah K. Algarzae, Amy C. Ladd, Ravindar R. Thomas, James P. Bennett
Mitochondrial Dna Copy Numbers In Pyramidal Neurons Are Decreased And Mitochondrial Biogenesis Transcriptome Signaling Is Disrupted In Alzheimer’S Disease Hippocampi, Ann C. Rice, Paula M. Keeney, Norah K. Algarzae, Amy C. Ladd, Ravindar R. Thomas, James P. Bennett
Neurology Publications
Alzheimer's disease (AD) is the major cause of adult-onset dementia and is characterized in its pre-diagnostic stage by reduced cerebral cortical glucose metabolism and in later stages by reduced cortical oxygen uptake, implying reduced mitochondrial respiration. Using quantitative PCR we determined the mitochondrial DNA (mtDNA) gene copy numbers from multiple groups of 15 or 20 pyramidal neurons, GFAP(+) astrocytes and dentate granule neurons isolated using laser capture microdissection, and the relative expression of mitochondrial biogenesis (mitobiogenesis) genes in hippocampi from 10 AD and 9 control (CTL) cases. AD pyramidal but not dentate granule neurons had significantly reduced mtDNA copy numbers …
Optimal Treatment Of Alzheimer's Disease Psychosis: Challenges And Solutions, Jeremy Koppel, Blaine Greenwald
Optimal Treatment Of Alzheimer's Disease Psychosis: Challenges And Solutions, Jeremy Koppel, Blaine Greenwald
Journal Articles
Psychotic symptoms emerging in the context of neurodegeneration as a consequence of Alzheimer's disease was recognized and documented by Alois Alzheimer himself in his description of the first reported case of the disease. Over a quarter of a century ago, in the context of attempting to develop prognostic markers of disease progression, psychosis was identified as an independent predictor of a more-rapid cognitive decline. This finding has been subsequently well replicated, rendering psychotic symptoms an important area of exploration in clinical history taking - above and beyond treatment necessity - as their presence has prognostic significance. Further, there is now …
The 12th Annual Pharmacogenetics In Psychiatry Meeting Report, J. Zhang, K. J. Aitchison, A. K. Malhotra
The 12th Annual Pharmacogenetics In Psychiatry Meeting Report, J. Zhang, K. J. Aitchison, A. K. Malhotra
Journal Articles
The 12th Annual Pharmacogenetics in Psychiatry meeting was held in Hollywood, Florida, from 31 May to 1 June 2013, in conjunction with the NCDEU meeting. It included a series of oral presentations as well as a poster session. This report summarizes the presentations at the conference. (C) 2014 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.
25-Hydroxyvitamin D And Cardiovascular Disease In Patients With Systemic Lupus Erythematosus: Data From A Large International Inception Cohort, A. Lertratanakul, P. Wu, A. Dyer, M. Urowitz, D. Gladman, C. Aranow, J. Font, R. Van Vollenhoven, T. Stoll, R. Ramsey-Goldman, +20 Additional Authors
25-Hydroxyvitamin D And Cardiovascular Disease In Patients With Systemic Lupus Erythematosus: Data From A Large International Inception Cohort, A. Lertratanakul, P. Wu, A. Dyer, M. Urowitz, D. Gladman, C. Aranow, J. Font, R. Van Vollenhoven, T. Stoll, R. Ramsey-Goldman, +20 Additional Authors
Journal Articles
Objective. An association between 25-hydroxyvitamin D (25[ OH] D; vitamin D) deficiency and increased cardiovascular (CV) risk factors and CV disease (CVD) has been shown in general population studies. Vitamin D deficiency has been noted in systemic lupus erythematosus (SLE), and CVD is a major cause of morbidity and mortality in SLE. The objectives of this study were to estimate the associations of 25(OH) D levels with CV risk factors and to determine whether low baseline 25(OH) D levels predict future CV events in patients participating in an international inception cohort. Methods. Data were collected on 890 participants, including demographics, …
Platelets Are Required For Enhanced Activation Of The Endothelium And Fibrinogen In A Mouse Thrombosis Model Of Aps, V. Proulle, R. A. Furie, G. Merrill-Skoloff, B. C. Furie, B. Furie
Platelets Are Required For Enhanced Activation Of The Endothelium And Fibrinogen In A Mouse Thrombosis Model Of Aps, V. Proulle, R. A. Furie, G. Merrill-Skoloff, B. C. Furie, B. Furie
Journal Articles
Antiphospholipid syndrome (APS) is defined by thrombosis, fetal loss, and the presence of antiphospholipid antibodies, including anti-beta 2-glycoprotein-1 autoantibodies (anti-beta 2GP1) that have a direct role in the pathogenesis of thrombosis in vivo. The cellular targets of the anti-beta 2GP1autoantibody/beta 2GP1complex in vivo were studied using a laser-induced thrombosis model of APS in a live mouse and human anti-beta 2GP1 autoantibodies affinity-purified from APS patients. Cell binding of fluorescently labeled beta 2GP1 and anti-beta 2GP1 autoantibodies revealed their colocalization on the platelet thrombus but not the endothelium. Anti-beta 2GP1 autoantibodies enhanced platelet activation, monitored by calcium mobilization, and endothelial activation, …
Spla2 Ib Induces Human Podocyte Apoptosis Via The M-Type Phospholipase A2 Receptor, Y. B. Pan, J. X. Wan, Y. P. Liu, Q. Yang, W. Liang, P. C. Singhal, M. A. Saleem, G. H. Ding
Spla2 Ib Induces Human Podocyte Apoptosis Via The M-Type Phospholipase A2 Receptor, Y. B. Pan, J. X. Wan, Y. P. Liu, Q. Yang, W. Liang, P. C. Singhal, M. A. Saleem, G. H. Ding
Journal Articles
The M-type phospholipase A2 receptor (PLA2R) is expressed in podocytes in human glomeruli. Group IB secretory phospholipase A2 (sPLA2 IB), which is one of the ligands of the PLA2R, is more highly expressed in chronic renal failure patients than in controls. However, the roles of the PLA2R and sPLA2 IB in the pathogenesis of glomerular diseases are unknown. In the present study, we found that more podocyte apoptosis occurs in the kidneys of patients with higher PLA2R and serum sPLA2 IB levels. In vitro, we demonstrated that human podocyte cells expressed the PLA2R in the cell membrane. After binding with …
Approaching The Next Revolution? Evolutionary Integration Of Neural And Immune Pathogen Sensing And Response, K. J. Tracey
Approaching The Next Revolution? Evolutionary Integration Of Neural And Immune Pathogen Sensing And Response, K. J. Tracey
Journal Articles
Mammalian immunity evolved by the process of natural selection that produced differential survival and reproduction advantages through combinations of hereditary traits underlying the response to pathogens. Primitive animals sense the presence of microbial pathogens through recognition of pathogen-derived molecules in their rudimentary immune and nervous systems. No molecular biological mechanism assigns primacy of pathogen sensing mechanisms to immune cells over neurons. Rather, in animals as diverse as Caenorhabditis elegans to mammals, neural reflexes are activated by the presence of pathogens and transduce neural mechanisms that control the development of immunity. A coming revolution in immunological thinking will require immunologists to …
Central Cholinergic Activation Of A Vagus Nerve-To-Spleen Circuit Alleviates Experimental Colitis, H. Ji, M. F. Rabbi, B. Labis, V. A. Pavlov, K. J. Tracey, J. E. Ghia
Central Cholinergic Activation Of A Vagus Nerve-To-Spleen Circuit Alleviates Experimental Colitis, H. Ji, M. F. Rabbi, B. Labis, V. A. Pavlov, K. J. Tracey, J. E. Ghia
Journal Articles
The cholinergic anti-inflammatory pathway is an efferent vagus nerve-based mechanism that regulates immune responses and cytokine production through alpha 7 nicotinic acetylcholine receptor (alpha 7nAChR) signaling. Decreased efferent vagus nerve activity is observed in inflammatory bowel disease. We determined whether central activation of this pathway alters inflammation in mice with colitis and the mediating role of a vagus nerve-to-spleen circuit and alpha 7nAChR signaling. Two experimental models of colitis were used in C57BL/6 mice. Central cholinergic activation induced by the acetylcholinesterase inhibitor galantamine or a muscarinic acetylcholine receptor agonist treatments resulted in reduced mucosal inflammation associated with decreased major histocompatibility …