7 results on '"Bhasin, Manoj K."'
Search Results
2. Specific Transcriptome Changes Associated with Blood Pressure Reduction in Hypertensive Patients After Relaxation Response Training.
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Bhasin, Manoj K., Denninger, John W., Huffman, Jeff C., Joseph, Marie G., Niles, Halsey, Chad-Friedman, Emma, Goldman, Roberta, Buczynski-Kelley, Beverly, Mahoney, Barbara A., Fricchione, Gregory L., Dusek, Jeffery A., Benson, Herbert, Zusman, Randall M., and Libermann, Towia A.
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HYPERTENSION genetics , *BIOMARKERS , *BLOOD pressure , *CLUSTER analysis (Statistics) , *FACTOR analysis , *FISHER exact test , *GENE expression , *HYPERTENSION , *LONGITUDINAL method , *PATH analysis (Statistics) , *PROBABILITY theory , *PSYCHOLOGICAL tests , *RELAXATION for health , *RESEARCH funding , *STATISTICAL hypothesis testing , *T-test (Statistics) , *GENOMICS , *RELAXATION techniques , *DATA analysis software , *GENE expression profiling - Abstract
Mind–body practices that elicit the relaxation response (RR) have been demonstrated to reduce blood pressure (BP) in essential hypertension (HTN) and may be an adjunct to antihypertensive drug therapy. However, the molecular mechanisms by which the RR reduces BP remain undefined.Objective: Genomic determinants associated with responsiveness to an 8-week RR-based mind–body intervention for lowering HTN in 13 stage 1 hypertensive patients classified as BP responders and 11 as nonresponders were identified.Design: Transcriptome analysis in peripheral blood mononuclear cells identified 1771 genes regulated by the RR in responders. Biological process- and pathway-based analysis of transcriptome data demonstrated enrichment in the following gene categories: immune regulatory pathways and metabolism (among downregulated genes); glucose metabolism, cardiovascular system development, and circadian rhythm (among upregulated genes). FurtherResults: in silico estimation of cell abundance from the microarray data showed enrichment of the anti-inflammatory M2 subtype of macrophages in BP responders. Nuclear factor-κB, vascular endothelial growth factor, and insulin were critical molecules emerging from interactive network analysis. These findings provide the first insights into the molecular mechanisms that are associated with the beneficial effects of the RR on HTN. [ABSTRACT FROM AUTHOR]Conclusions: - Published
- 2018
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3. Upregulation of inflammatory gene transcripts in periosteum of chronic migraineurs: Implications for extracranial origin of headache.
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Perry, Carlton J., Blake, Pamela, Buettner, Catherine, Papavassiliou, Efstathios, Schain, Aaron J., Bhasin, Manoj K., and Burstein, Rami
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DOPA ,CELL receptors ,CEPHALOSPORINS ,CHRONIC diseases ,FASTING ,GENE expression ,INFLAMMATION ,ISOFLURANE ,MIGRAINE ,PERIOSTEUM ,PROTEINS ,RESEARCH funding ,CASE-control method ,GENE expression profiling ,PHARMACODYNAMICS - Abstract
Objective: Chronic migraine (CM) is often associated with chronic tenderness of pericranial muscles. A distinct increase in muscle tenderness prior to onset of occipital headache that eventually progresses into a full-blown migraine attack is common. This experience raises the possibility that some CM attacks originate outside the cranium. The objective of this study was to determine whether there are extracranial pathophysiologies in these headaches.Methods: We biopsied and measured the expression of gene transcripts (mRNA) encoding proteins that play roles in immune and inflammatory responses in affected (ie, where the head hurts) calvarial periosteum of (1) patients whose CMs are associated with muscle tenderness and (2) patients with no history of headache.Results: Expression of proinflammatory genes (eg, CCL8, TLR2) in the calvarial periosteum significantly increased in CM patients attesting to muscle tenderness, whereas expression of genes that suppress inflammation and immune cell differentiation (eg, IL10RA, CSF1R) decreased.Interpretation: Because the upregulated genes were linked to activation of white blood cells, production of cytokines, and inhibition of NF-κB, and the downregulated genes were linked to prevention of macrophage activation and cell lysis, we suggest that the molecular environment surrounding periosteal pain fibers is inflamed and in turn activates trigeminovascular nociceptors that reach the affected periosteum through suture branches of intracranial meningeal nociceptors and/or somatic branches of the occipital nerve. This study provides the first set of evidence for localized extracranial pathophysiology in CM. Ann Neurol 2016;79:1000-1013. [ABSTRACT FROM AUTHOR]- Published
- 2016
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4. Novel non-invasive biomarkers that distinguish between benign prostate hyperplasia and prostate cancer.
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Jedinak, Andrej, Curatolo, Adam, Zurakowski, David, Dillon, Simon, Bhasin, Manoj K., Libermann, Towia A., Roy, Roopali, Sachdev, Monisha, Loughlin, Kevin R., and Moses, Marsha A.
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PROSTATE cancer ,BIOMARKERS ,HYPERPLASIA ,GENE expression ,URINALYSIS - Abstract
Background: The objective of this study was to discover and to validate novel noninvasive biomarkers that distinguish between benign prostate hyperplasia (BPH) and localized prostate cancer (PCa), thereby helping to solve the diagnostic dilemma confronting clinicians who treat these patients. Methods: Quantitative iTRAQ LC/LC/MS/MS analysis was used to identify proteins that are differentially expressed in the urine of men with BPH compared with those who have localized PCa. These proteins were validated in 173 urine samples from patients diagnosed with BPH (N = 83) and PCa (N = 90). Multivariate logistic regression analysis was used to identify the predictive biomarkers. Results: Three proteins, β2M, PGA3, and MUC3 were identified by iTRAQ and validated by immunoblot analyses. Univariate analysis demonstrated significant elevations in urinary β2M (P < 0.001), PGA3 (P = 0.006), and MUC3 (P = 0.018) levels found in the urine of PCa patients. Multivariate logistic regression analysis revealed AUC values ranging from 0.618 for MUC3 (P = 0.009), 0.625 for PGA3 (P < 0.008), and 0.668 for β2M (P < 0.001). The combination of all three demonstrated an AUC of 0.710 (95% CI: 0.631 - 0.788, P< 0.001); diagnostic accuracy improved even more when these data were combined with PSA categories (AUC = 0.812, (95% CI: 0.740 - 0.885, P < 0.001). Conclusions: Urinary β2M, PGA3, and MUC3, when analyzed alone or when multiplexed with clinically defined categories of PSA, may be clinically useful in noninvasively resolving the dilemma of effectively discriminating between BPH and localized PCa. [ABSTRACT FROM AUTHOR]
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- 2015
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5. Functional Genomics in the Study of Mind-Body Therapies.
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Niles, Halsey, Mehta, Darshan H., Corrigan, Alexandra A., Bhasin, Manoj K., and Denninger, John W.
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FUNCTIONAL genomics ,MIND & body therapies ,IMMUNE system ,HEALTH promotion ,NF-kappa B ,GENE expression - Abstract
Background: Mind-body therapies (MBTs) are used throughout the world in treatment, disease prevention, and health promotion. However, the mechanisms by which MBTs exert their positive effects are not well understood. Investigations into MBTs using functional genomics have revolutionized the understanding of MBT mechanisms and their effects on human physiology. Methods: We searched the literature for the effects of MBTs on functional genomics determinants using MEDLINE, supplemented by a manual search of additional journals and a reference list review. Results: We reviewed 15 trials that measured global or targeted transcriptomic, epigenomic, or proteomic changes in peripheral blood. Sample sizes ranged from small pilot studies (n=2) to large trials (n=500). While the reliability of individual genes from trial to trial was often inconsistent, genes related to inflammatory response, particularly those involved in the nuclear factor-kappa B (NF-κB) pathway, were consistently downregulated across most studies. Conclusion: In general, existing trials focusing on gene expression changes brought about by MBTs have revealed intriguing connections to the immune system through the NF-κB cascade, to telomere maintenance, and to apoptotic regulation. However, these findings are limited to a small number of trials and relatively small sample sizes. More rigorous randomized controlled trials of healthy subjects and specific disease states are warranted. Future research should investigate functional genomics areas both upstream and downstream of MBT-related gene expression changes--from epigenomics to proteomics and metabolomics. [ABSTRACT FROM AUTHOR]
- Published
- 2014
6. Analysis of Host Gene Expression Changes Reveals Distinct Roles for the Cytoplasmic Domain of the Epstein-Barr Virus Receptor/CD21 in B-Cell Maturation, Activation, and Initiation of Virus Infection.
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Arredouani, Mohamed S., Bhasin, Manoj K., Sage, David R., Dunn, Laura K., Gill, Michael B., Agnani, Deep, Libermann, Towia A., and Fingeroth, Joyce D.
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GENE expression , *CYTOPLASM , *EPSTEIN-Barr virus , *B cells , *VIRUS diseases - Abstract
Epstein-Barr virus (EBV) attachment to human CD21 on the B-cell surface initiates infection. Whether CD21 is a simple tether or conveys vital information to the cell interior for production of host factors that promote infection of primary B cells is controversial, as the cytoplasmic fragment of CD21 is short, though highly conserved. The ubiquity of CD21 on normal B cells, the diversity of this population, and the well-known resistance of primary B cells to gene transfer technologies have all impeded resolution of this question. To uncover the role(s) of the CD21 cytoplasmic domain during infection initiation, the full-length receptor (CD21 = CR), a mutant lacking the entire cytoplasmic tail (CT), and a control vector (NEO) were stably expressed in two pre-B-cell lines that lack endogenous receptor. Genome-wide transcriptional analysis demonstrated that stable CD21 surface expression alone (either CR or CT) produced multiple independent changes in gene expression, though both dramatically decreased class I melanoma-associated antigen (MAGE) family RNAs and upregulated genes associated with B-cell differentiation (e.g., C2TA, HLA-II, IL21R, MIC2, CD48, and PTPRCAP/CD45-associated protein). Temporal analysis spanning 72 h revealed that not only CR- but also CT-expressing lines initiated latency. In spite of this, the number and spectrum of transcripts altered in CR- compared with CT-bearing lines at 1 h after infection further diverged. Differential modulation of immediate early cellular transcripts (e.g., c-Jun and multiple histones), both novel and previously linked to CD21-initiated signaling, as well as distinct results from pathway analyses support a separate role for the cytoplasmic domain in initiation of intracellular signals. [ABSTRACT FROM AUTHOR]
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- 2014
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7. Transcriptional Patterns in Peritoneal Tissue of Encapsulating Peritoneal Sclerosis, a Complication of Chronic Peritoneal Dialysis.
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Reimold, Fabian R., Braun, Niko, Zsengellér, Zsuzsanna K., Stillman, Isaac E., Karumanchi, S. Ananth, Toka, Hakan R., Latus, Joerg, Fritz, Peter, Biegger, Dagmar, Segerer, Stephan, Alscher, M. Dominik, Bhasin, Manoj K., and Alper, Seth L.
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PERITONEAL dialysis ,BOWEL obstructions ,GENETIC transcription ,DENDRITIC cells ,B cells ,REVERSE transcriptase polymerase chain reaction ,CELL proliferation - Abstract
Encapsulating peritoneal sclerosis (EPS) is a devastating complication of peritoneal dialysis (PD), characterized by marked inflammation and severe fibrosis of the peritoneum, and associated with high morbidity and mortality. EPS can occur years after termination of PD and, in severe cases, leads to intestinal obstruction and ileus requiring surgical intervention. Despite ongoing research, the pathogenesis of EPS remains unclear. We performed a global transcriptome analysis of peritoneal tissue specimens from EPS patients, PD patients without EPS, and uremic patients without history of PD or EPS (Uremic). Unsupervised and supervised bioinformatics analysis revealed distinct transcriptional patterns that discriminated these three clinical groups. The analysis identified a signature of 219 genes expressed differentially in EPS as compared to PD and Uremic groups. Canonical pathway analysis of differentially expressed genes showed enrichment in several pathways, including antigen presentation, dendritic cell maturation, B cell development, chemokine signaling and humoral and cellular immunity (P value<0.05). Further interactive network analysis depicted effects of EPS-associated genes on networks linked to inflammation, immunological response, and cell proliferation. Gene expression changes were confirmed by qRT-PCR for a subset of the differentially expressed genes. EPS patient tissues exhibited elevated expression of genes encoding sulfatase1, thrombospondin 1, fibronectin 1 and alpha smooth muscle actin, among many others, while in EPS and PD tissues mRNAs encoding leptin and retinol-binding protein 4 were markedly down-regulated, compared to Uremic group patients. Immunolocalization of Collagen 1 alpha 1 revealed that Col1a1 protein was predominantly expressed in the submesothelial compact zone of EPS patient peritoneal samples, whereas PD patient peritoneal samples exhibited homogenous Col1a1 staining throughout the tissue samples. The results are compatible with the hypothesis that encapsulating peritoneal sclerosis is a distinct pathological process from the simple peritoneal fibrosis that accompanies all PD treatment. [ABSTRACT FROM AUTHOR]
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- 2013
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