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Semapimod Sensitizes Glioblastoma Tumors To Ionizing Radiation By Targeting Microglia, I. S. Miller, S. Didier, D. W. Murray, T. H. Turner, M. Issaivanan, R. Ruggieri, Y. Al-Abed, M. Symons Jan 2014

Semapimod Sensitizes Glioblastoma Tumors To Ionizing Radiation By Targeting Microglia, I. S. Miller, S. Didier, D. W. Murray, T. H. Turner, M. Issaivanan, R. Ruggieri, Y. Al-Abed, M. Symons

Journal Articles

Glioblastoma is the most malignant and lethal form of astrocytoma, with patients having a median survival time of approximately 15 months with current therapeutic modalities. It is therefore important to identify novel therapeutics. There is mounting evidence that microglia (specialized brain-resident macrophages) play a significant role in the development and progression of glioblastoma tumors. In this paper we show that microglia, in addition to stimulating glioblastoma cell invasion, also promote glioblastoma cell proliferation and resistance to ionizing radiation in vitro. We found that semapimod, a drug that selectively interferes with the function of macrophages and microglia, potently inhibits microglia-stimulated GL261 …

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Terror Medicine As Part Of The Medical School Curriculum, L. A. Cole, K. Wagner, S. Scott, N. D. Connell, A. Cooper, C. A. Kennedy, B. Natal, S. Lamba Jan 2014

Terror Medicine As Part Of The Medical School Curriculum, L. A. Cole, K. Wagner, S. Scott, N. D. Connell, A. Cooper, C. A. Kennedy, B. Natal, S. Lamba

Journal Articles

Terror medicine, a field related to emergency and disaster medicine, focuses on medical issues ranging from preparedness to psychological manifestations specifically associated with terrorist attacks. Calls to teach aspects of the subject in American medical schools surged after the 2001 jetliner and anthrax attacks. Although the threat of terrorism persists, terror medicine is still addressed erratically if at all in most medical schools. This paper suggests a template for incorporating the subject throughout a 4-year medical curriculum. The instructional framework culminates in a short course for fourth year students, such as one recently introduced at Rutgers New Jersey Medical School, …

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Aicar Attenuates Organ Injury And Inflammatory Response After Intestinal Ischemia And Reperfusion, J. P. Idrovo, W.L. Yang, A. Jacob, M. Aziz, Jeffrey Nicastro, Gene Coppa, P. Wang Jan 2014

Aicar Attenuates Organ Injury And Inflammatory Response After Intestinal Ischemia And Reperfusion, J. P. Idrovo, W.L. Yang, A. Jacob, M. Aziz, Jeffrey Nicastro, Gene Coppa, P. Wang

Journal Articles

Intestinal ischemia and reperfusion (I/R) is encountered in various clinical conditions and contributes to multiorgan failure and mortality as high as 60% to 80%. Intestinal I/R not only injures the intestine, but affects remote organs such as the lung leading to acute lung injury. The development of novel and effective therapies for intestinal I/R are critical for the improvement of patient outcome. AICAR (5-aminoimidazole-4-carboxyamide ribonucleoside) is a cell-permeable compound that has been shown to possess antiinflammatory effects. The objective is to determine that treatment with AICAR attenuates intestinal I/R injury and subsequent acute lung injury (ALI). Male Sprague Dawley rats …

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Gene Therapy In Patient-Specific Stem Cell Lines And A Preclinical Model Of Retinitis Pigmentosa With Membrane Frizzled-Related Protein Defects, Y. Li, W. H. Wu, C. W. Hsu, H. V. Nguyen, Y. T. Tsai, L. Chan, T. Nagasaki, I. H. Maumenee, L. A. Yannuzzi, S. H. Tsang, +3 Additional Authors Jan 2014

Gene Therapy In Patient-Specific Stem Cell Lines And A Preclinical Model Of Retinitis Pigmentosa With Membrane Frizzled-Related Protein Defects, Y. Li, W. H. Wu, C. W. Hsu, H. V. Nguyen, Y. T. Tsai, L. Chan, T. Nagasaki, I. H. Maumenee, L. A. Yannuzzi, S. H. Tsang, +3 Additional Authors

Journal Articles

Defects in Membrane Frizzled-related Protein (MFRP) cause autosomal recessive retinitis pigmentosa (RP). MFRP codes for a retinal pigment epithelium (RPE)-specific membrane receptor of unknown function. In patient-specific induced pluripotent stem (iPS)-derived RPE cells, precise levels of MFRP, and its dicistronic partner CTRP5, are critical to the regulation of actin organization. Overexpression of CTRP5 in naive human RPE cells phenocopied behavior of MFRP-deficient patient RPE (iPS-RPE) cells. AAV8 (Y733F) vector expressing human MFRP rescued the actin disorganization phenotype and restored apical microvilli in patient-specific iPS-RPE cell lines. As a result, AAV-treated MFRP mutant iPS-RPE recovered pigmentation and transepithelial resistance. The efficacy …

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Network Modulation Following Sham Surgery In Parkinson's Disease, J. H. Ko, A. Feigin, P. Mattis, C. C. Tang, Y. L. Ma, V. Dhawan, M. J. During, M. G. Kaplitt, D. Eidelberg Jan 2014

Network Modulation Following Sham Surgery In Parkinson's Disease, J. H. Ko, A. Feigin, P. Mattis, C. C. Tang, Y. L. Ma, V. Dhawan, M. J. During, M. G. Kaplitt, D. Eidelberg

Journal Articles

Patient responses to placebo and sham effects are a major obstacle to the development of therapies for brain disorders, including Parkinson's disease (PD). Here, we used functional brain imaging and network analysis to study the circuitry underlying placebo effects in PD subjects randomized to sham surgery as part of a double-blind gene therapy trial. Metabolic imaging was performed prior to randomization, then again at 6 and 12 months after sham surgery. In this cohort, the sham response was associated with the expression of a distinct cerebello-limbic circuit. The expression of this network increased consistently in patients blinded to treatment and …

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Characterization Of Disease-Related Covariance Topographies With Ssmpca Toolbox: Effects Of Spatial Normalization And Pet Scanners, S. C. Peng, Y. L. Ma, P. G. Spetsieris, P. Mattis, Andrew Feigin, V. Dhawan, D. Eidelberg Jan 2014

Characterization Of Disease-Related Covariance Topographies With Ssmpca Toolbox: Effects Of Spatial Normalization And Pet Scanners, S. C. Peng, Y. L. Ma, P. G. Spetsieris, P. Mattis, Andrew Feigin, V. Dhawan, D. Eidelberg

Journal Articles

To generate imaging biomarkers from disease-specific brain networks, we have implemented a general toolbox to rapidly perform scaled subprofile modeling (SSM) based on principal component analysis (PCA) on brain images of patients and normals. This SSMPCA toolbox can define spatial covariance patterns whose expression in individual subjects can discriminate patients from controls or predict behavioral measures. The technique may depend on differences in spatial normalization algorithms and brain imaging systems. We have evaluated the reproducibility of characteristic metabolic patterns generated by SSMPCA in patients with Parkinson's disease (PD). We used [F-18]fluorodeoxyglucose PET scans from patients with PD and normal controls. …

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Angiopoietin-2: A Key To Understanding Sepsis And Its Pulmonary Sequelae?, J. Y. Lee, E. J. Miller Jan 2014

Angiopoietin-2: A Key To Understanding Sepsis And Its Pulmonary Sequelae?, J. Y. Lee, E. J. Miller

Journal Articles

No abstract provided.

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Apol1 Risk Variants Enhance Podocyte Necrosis Through Compromising Lysosomal Membrane Permeability, X. Q. Lan, A. Jhaveri, K. Cheng, H. X. Wen, M. A. Saleem, P. W. Mathieson, S. Aviram, A. Malhotra, K. Skorecki, P. C. Singhal, +1 Additional Author Jan 2014

Apol1 Risk Variants Enhance Podocyte Necrosis Through Compromising Lysosomal Membrane Permeability, X. Q. Lan, A. Jhaveri, K. Cheng, H. X. Wen, M. A. Saleem, P. W. Mathieson, S. Aviram, A. Malhotra, K. Skorecki, P. C. Singhal, +1 Additional Author

Journal Articles

Development of higher rates of nondiabetic glomerulosclerosis (GS) in African Americans has been attributed to two coding sequence variants (G1 and G2) in the APOL1 gene. To date, the cellular function and the role of APOL1 variants (Vs) in GS are still unknown. In this study, we examined the effects of overexpressing wild-type (G0) and kidney disease risk variants (G1 and G2) of APOL1 in human podocytes using a lentivirus expression system. Interestingly, G0 inflicted podocyte injury only at a higher concentration; however, G1 and G2 promoted moderate podocyte injury at lower and higher concentrations. APOL1Vs expressing podocytes displayed diffuse …

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B-1a Cell Diversity: Nontemplated Addition In B-1a Cell Ig Is Determined By Progenitor Population And Developmental Location, N. E. Holodick, T. Vizconde, T. L. Rothstein Jan 2014

B-1a Cell Diversity: Nontemplated Addition In B-1a Cell Ig Is Determined By Progenitor Population And Developmental Location, N. E. Holodick, T. Vizconde, T. L. Rothstein

Journal Articles

Natural Abs produced by B-1a cells are required for immediate protection against infection. The protective capacity of natural Abs is attributed to germline-like structure, which includes the relative absence of N-region addition. Previous studies have shown B-1a cell Ig from aged mice contains abundant nontemplated (N)-additions. B-1a cells have been shown to derive from a specific lineage-negative (Lin(-)) CD45R(low/-) CD19(+) progenitor found both in fetal liver and adult bone marrow. In this study, we report identification of a fetal liver population characterized phenotypically as Lin(-)CD45R(-)CD19(-), which gives rise to IgM(+)IgD(low)CD45R(low)CD5(+)Mac-1(+)CD19(high)CD43(+)CD23(low) B-1a cells upon adoptive transfer to SCID recipients. These B-1a …

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A Comparison Of The Malignancy Incidence Among Patients With Psoriatic Arthritis And Patients With Rheumatoid Arthritis In A Large Us Cohort, R. L. Gross, J. S. Schwartzman-Morris, M. Krathen, G. Reed, H. Chang, K. C. Saunders, M. C. Fisher, J. D. Greenberg, C. Putterman, A. Broder, +3 Additional Authors Jan 2014

A Comparison Of The Malignancy Incidence Among Patients With Psoriatic Arthritis And Patients With Rheumatoid Arthritis In A Large Us Cohort, R. L. Gross, J. S. Schwartzman-Morris, M. Krathen, G. Reed, H. Chang, K. C. Saunders, M. C. Fisher, J. D. Greenberg, C. Putterman, A. Broder, +3 Additional Authors

Journal Articles

OBJECTIVE: To compare the incidence rates of malignancy among patients with psoriatic arthritis (PsA) and patients with rheumatoid arthritis (RA) in the Consortium of Rheumatology Researchers of North America (CORRONA) registry. METHODS: We analyzed 2,970 patients with PsA (7,133 patient-years of followup) and 19,260 patients with RA (53,864 patient-years of followup). Using a standardized adjudication process, we identified 40 confirmed malignancies in the patients with PsA and 307 confirmed malignancies in those with RA. Incidence rates were calculated per 100 patient-years. Incidence rate ratios were estimated, with adjustment for age, sex, disease duration, body mass index, disease activity, year of …

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Coupling To A Glioblastoma-Directed Antibody Potentiates Antitumor Activity Of Curcumin, P. Langone, P. R. Debata, J. D. Inigo, S. Dolai, S. Mukherjee, P. Halat, K. Mastroianni, G. M. Curcio, M. R. Castellanos, K. Raja, P. Banerjee Jan 2014

Coupling To A Glioblastoma-Directed Antibody Potentiates Antitumor Activity Of Curcumin, P. Langone, P. R. Debata, J. D. Inigo, S. Dolai, S. Mukherjee, P. Halat, K. Mastroianni, G. M. Curcio, M. R. Castellanos, K. Raja, P. Banerjee

Journal Articles

Current therapies for glioblastoma are largely palliative, involving surgical resection followed by chemotherapy and radiation therapy, which yield serious side effects and very rarely produce complete recovery. Curcumin, a food component, blocked brain tumor formation but failed to eliminate established brain tumors in vivo, probably because of its poor bioavailability. In the glioblastoma GL261 cells, it suppressed the tumor-promoting proteins NF-kappa B, P-Akt1, vascular endothelial growth factor, cyclin D1 and BClXL and triggered cell death. Expression of exogenous p50 and p65 subunits of NF-kappa B conferred partial protection on transfected GL261 cells against curcumin insult, indicating that NF-kappa B played …

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Depression In Pulmonary Arterial Hypertension And Interstitial Lung Diseases, S. Verma, J. Cardenas-Garcia, P. R. Mohapatra, A. Talwar Jan 2014

Depression In Pulmonary Arterial Hypertension And Interstitial Lung Diseases, S. Verma, J. Cardenas-Garcia, P. R. Mohapatra, A. Talwar

Journal Articles

Advanced lung diseases such as pulmonary arterial hypertension (PAH) and interstitial lung diseases (ILD) are chronic diseases that cause significantly high morbidity and mortality. As a result, patients can undergo some psychological changes leading to a poor quality of life and depression. Diagnosis of depression is often obscured because fatigue and apathy, two common symptoms of depression, frequently overlap with PAH and ILD. Healthcare providers are sometimes reluctant to ask or mistakenly believe that these symptoms are part of the ongoing disease process, rather than a serious condition like depression. Screening tools are available for physicians to be well positioned …

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Dose-Escalation Of Human Anti-Interferon-Alpha Receptor Monoclonal Antibody Medi-546 In Subjects With Systemic Sclerosis: A Phase 1, Multicenter, Open Label Study, A. Goldberg, T. Geppert, E. Schiopu, T. Frech, V. Hsu, R. W. Simms, S. L. Peng, Y. H. Yao, N. Elgeioushi, S. Yoo, +2 Additional Authors Jan 2014

Dose-Escalation Of Human Anti-Interferon-Alpha Receptor Monoclonal Antibody Medi-546 In Subjects With Systemic Sclerosis: A Phase 1, Multicenter, Open Label Study, A. Goldberg, T. Geppert, E. Schiopu, T. Frech, V. Hsu, R. W. Simms, S. L. Peng, Y. H. Yao, N. Elgeioushi, S. Yoo, +2 Additional Authors

Journal Articles

Introduction: Type I interferons (IFNs) are implicated in the pathogenesis of systemic sclerosis (SSc). MEDI-546 is an investigational human monoclonal antibody directed against the type I IFN receptor. This Phase 1 study evaluated the safety/tolerability, pharmacokinetics (PK), immunogenicity, and pharmacodynamics (PD) of single and multiple intravenous doses of MEDI-546 in adults with SSc. Methods: Subjects (>= 18 years) with SSc were enrolled in an open-label, dose-escalation study to receive single (0.1, 0.3, 1.0, 3.0, 10.0, or 20.0 mg/kg), or 4 weekly intravenous doses (0.3, 1.0, or 5.0 mg/kg/week) of MEDI-546. Subjects were followed for 12 weeks. Safety assessments included …

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Effects Of Prostaglandin E-2 On P53 Mrna Transcription And P53 Mutagenesis During T-Cell-Independent Human B-Cell Clonal Expansion, S. Haque, X. J. Yan, L. Rosen, S. Mccormick, N. Chiorazzi, P. K. A. Mongini Jan 2014

Effects Of Prostaglandin E-2 On P53 Mrna Transcription And P53 Mutagenesis During T-Cell-Independent Human B-Cell Clonal Expansion, S. Haque, X. J. Yan, L. Rosen, S. Mccormick, N. Chiorazzi, P. K. A. Mongini

Journal Articles

Within T-cell-dependent germinal centers, p53 gene transcription is repressed by Bcl-6 and is thus less vulnerable to mutation. Malignant lymphomas within inflamed extranodal sites exhibit a relatively high incidence of p53 mutations. The latter might originate from normal B-cell clones manifesting activation-induced cytosine deaminase (AID) and up-regulated p53 following T-cell-independent (TI) stimulation. We here examine p53 gene transcription in such TI clones, with a focus on modulatory effects of prostaglandin E-2 (PGE(2)), and evaluate progeny for p53 mutations. Resting IgM(+)IgD(+)CD27(-) B cells from human tonsils were labeled with CFSE and stimulated in vitro with complement-coated antigen surrogate, IL-4, and BAFF …

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Enhanced Nicotinic Receptor Mediated Relaxations In Gastroesophageal Muscle Fibers From Barrett's Esophagus Patients, L. S. Miller, A. K. Vegesna, A. S. Braverman, M. F. Barbe, M. R. Ruggieri Jan 2014

Enhanced Nicotinic Receptor Mediated Relaxations In Gastroesophageal Muscle Fibers From Barrett's Esophagus Patients, L. S. Miller, A. K. Vegesna, A. S. Braverman, M. F. Barbe, M. R. Ruggieri

Journal Articles

No abstract provided.

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Ethnic Disparities In The Risk Of Colorectal Adenomas Associated With Aspirin And Statin Use: A Retrospective Multiethnic Study, A. H. Davis-Yadley, S. Lipka, H. Shen, H. Shah, S. Swarup, A. Barnowsky, J. Silpe, A. Abraham, P. Viswanathan, B. Krishnamachari, +4 Additional Authors Jan 2014

Ethnic Disparities In The Risk Of Colorectal Adenomas Associated With Aspirin And Statin Use: A Retrospective Multiethnic Study, A. H. Davis-Yadley, S. Lipka, H. Shen, H. Shah, S. Swarup, A. Barnowsky, J. Silpe, A. Abraham, P. Viswanathan, B. Krishnamachari, +4 Additional Authors

Journal Articles

BACKGROUND: Although data on the inverse association between colorectal adenomas (CRA) and daily aspirin or statin therapy exists in white and black patients, scarce data exists on these associations in the Hispanic population. With a rapidly increasing Hispanic population in the United States, defining the association in Hispanics is crucial. METHODS: The study sample included 1,843 consecutive patients who underwent a colonoscopy (screening or diagnostic) from 2009 to 2011 at a community hospital in East Meadow, New York. Data was then extracted from patient charts regarding aspirin and/or statin use. Adjusted odds ratios (OR) and their 95% confidence intervals (CI) …

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The Gut Microbiota Influences Blood-Brain Barrier Permeability In Mice, V. Braniste, M. Al-Asmakh, C. Kowal, F. Anuar, A. Abbaspour, M. Toth, A. Korecka, B. T. Volpe, B. Diamond, S. Pettersson, +8 Additional Authors Jan 2014

The Gut Microbiota Influences Blood-Brain Barrier Permeability In Mice, V. Braniste, M. Al-Asmakh, C. Kowal, F. Anuar, A. Abbaspour, M. Toth, A. Korecka, B. T. Volpe, B. Diamond, S. Pettersson, +8 Additional Authors

Journal Articles

Pivotal to brain development and function is an intact blood-brain barrier (BBB), which acts as a gatekeeper to control the passage and exchange of molecules and nutrients between the circulatory system and the brain parenchyma. The BBB also ensures homeostasis of the central nervous system (CNS). We report that germ-free mice, beginning with intrauterine life, displayed increased BBB permeability compared to pathogen-free mice with a normal gut flora. The increased BBB permeability was maintained in germ-free mice after birth and during adulthood and was associated with reduced expression of the tight junction proteins occludin and claudin-5, which are known to …

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Histological Healing Favors Lower Risk Of Colon Carcinoma In Extensive Ulcerative Colitis, B. I. Korelitz, K. Sultan, M. Kothari, L. Arapos, J. Schneider, G. Panagopoulos Jan 2014

Histological Healing Favors Lower Risk Of Colon Carcinoma In Extensive Ulcerative Colitis, B. I. Korelitz, K. Sultan, M. Kothari, L. Arapos, J. Schneider, G. Panagopoulos

Journal Articles

AIM: To search for the answer in extensive ulcerative colitis as to whether histological inflammation persisting despite endoscopic mucosal healing serves to increase the risk of colon cancer (CC) or high grade dysplasia (HGD). METHODS: This is a single center (Lenox Hill Hospital) retrospective cohort and descriptive study of extensive ulcerative colitis (UC) for 20 years or more with a minimum of 3 surveillance colonoscopies and biopsies performed after the first 10 years of UC diagnosis. Data analyzed included: duration of UC, date of diagnosis of (CC) or (HGD), number of surveillance colonoscopies, and biopsies showing histological inflammation and its …

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Hormonal Milieu At Time Of B Cell Activation Controls Duration Of Autoantibody Response, V. Jeganathan, E. Peeva, B. Diamond Jan 2014

Hormonal Milieu At Time Of B Cell Activation Controls Duration Of Autoantibody Response, V. Jeganathan, E. Peeva, B. Diamond

Journal Articles

A strong gender bias is seen in many autoimmune diseases including systemic lupus erythematosus (SLE). To investigate the basis for the female preponderance in SLE, we have been studying BALB/c mice in which B cells express the R4A heavy chain of an anti-DNA antibody in association with an endogenous light chain repertoire (R4Atg mice). In unmanipulated mice, approximately 5% of B cells express the R4A transgene. R4Atg mice do not spontaneously develop elevated serum titers of anti-DNA antibodies. Administration of either estradiol (E2) or prolactin (Pr) results in escape from tolerance of autoreactive B cells, expressed as an increase in …

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Identification Of Stage-Specific Genes Associated With Lupus Nephritis And Response To Remission Induction In (Nzb X Nzw)F1 And Nzm2410 Mice, R. Bethunaickan, C. C. Berthier, W. J. Zhang, R. Eksi, H. D. Li, Y. F. Guan, M. Kretzler, A. Davidson Jan 2014

Identification Of Stage-Specific Genes Associated With Lupus Nephritis And Response To Remission Induction In (Nzb X Nzw)F1 And Nzm2410 Mice, R. Bethunaickan, C. C. Berthier, W. J. Zhang, R. Eksi, H. D. Li, Y. F. Guan, M. Kretzler, A. Davidson

Journal Articles

Objective. To elucidate the molecular mechanisms involved in renal inflammation during the progression, remission, and relapse of nephritis in murine lupus models using transcriptome analysis. Methods. Kidneys from (NZB x NZW)F1 (NZB/NZW) and NZM2410 mice were harvested at intervals during the disease course or after remission induction. Genome-wide expression profiles were obtained from microarray analysis of perfused kidneys. Real-time polymerase chain reaction (PCR) analysis for selected genes was used to validate the microarray data. Comparisons between groups using SAM, and unbiased analysis of the entire data set using singular value decomposition and self-organizing maps were performed. Results. Few changes in …

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Iso-66, A Novel Inhibitor Of Macrophage Migration Inhibitory Factor, Shows Efficacy In Melanoma And Colon Cancer Models, K. Ioannou, K. F. Cheng, G. V. Crichlow, A. I. Birmpilis, E. J. Lolis, O. E. Tsitsilonis, Y. Al-Abed Jan 2014

Iso-66, A Novel Inhibitor Of Macrophage Migration Inhibitory Factor, Shows Efficacy In Melanoma And Colon Cancer Models, K. Ioannou, K. F. Cheng, G. V. Crichlow, A. I. Birmpilis, E. J. Lolis, O. E. Tsitsilonis, Y. Al-Abed

Journal Articles

Macrophage migration inhibitory factor (MIF) is a pleiotropic pro-inflammatory cytokine, which possesses a contributing role in cancer progression and metastasis and, thus, is now considered a promising anticancer drug target. Many MIF-inactivating strategies have proven successful in delaying cancer growth. Here, we report on the synthesis of ISO-66, a novel, highly stable, small-molecule MIF inhibitor, an analog of ISO-1 with improved characteristics. The MIF:ISO-66 co-crystal structure demonstrated that ISO-66 ligates the tautomerase active site of MIF, which has previously been shown to play an important role in its biological functions. In vitro, ISO-66 enhanced specific and non-specific anticancer immune responses, …

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Mif: Mood Improving/Inhibiting Factor?, J. Bloom, Y. Al-Abed Jan 2014

Mif: Mood Improving/Inhibiting Factor?, J. Bloom, Y. Al-Abed

Journal Articles

Although major depressive disorder imposes a serious public health burden and affects nearly one in six individuals in developed countries over their lifetimes, there is still no consensus on its pathophysiology. Inflammation and cytokines have emerged as a promising new avenue in depression research, and, in particular, macrophage migration inhibitory factor (MIF) has been shown to be significant in depression physiology. In this review we summarize current research on MIF and depression. We highlight the arguments for MIF as a pro-and antidepressant species and discuss the potential implications for therapeutics.

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Modulation Of Renin Angiotensin System Predominantly Alters Sclerotic Phenotype Of Glomeruli In Hivan, A. Plagov, X. Q. Lan, P. Rai, D. Kumar, R. Lederman, S. Rehman, A. Malhotra, G. H. Ding, P. N. Chander, P. C. Singhal Jan 2014

Modulation Of Renin Angiotensin System Predominantly Alters Sclerotic Phenotype Of Glomeruli In Hivan, A. Plagov, X. Q. Lan, P. Rai, D. Kumar, R. Lederman, S. Rehman, A. Malhotra, G. H. Ding, P. N. Chander, P. C. Singhal

Journal Articles

HIV-associated nephropathy (HIVAN) is a common complication of HIV-1 infection in patients with African ancestry in general and with APOL1 gene risk variants in particular. Although collapsing glomerulopathy is considered a hallmark of HIVAN, significant numbers of glomeruli in patients with HIVAN also display other variants of focal segmental glomerulosclerosis (FSGS). We propose that collapsed glomeruli as well as glomeruli with other variants of FSGS are manifestations of HIVAN and their prevalence depends on associated host factors. We explored the role of the renin-angiotensin system (RAS) in the manifestation of any specific glomerular phenotype in HIVAN. To evaluate the role …

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Nf-Kappa B-To-Ap-1 Switch: A Mechanism Regulating Transition From Endothelial Barrier Injury To Repair In Endotoxemic Mice, G. Liu, X. B. Ye, E. J. Miller, S. F. Liu Jan 2014

Nf-Kappa B-To-Ap-1 Switch: A Mechanism Regulating Transition From Endothelial Barrier Injury To Repair In Endotoxemic Mice, G. Liu, X. B. Ye, E. J. Miller, S. F. Liu

Journal Articles

Endothelial barrier disruption is a hallmark of multiple organ injury (MOI). However, mechanisms governing the restoration of endothelial barrier function are poorly understood. Here, we uncovered an NF-kappa B-to-AP-1 switch that regulates the transition from barrier injury to repair following endotoxemic MOI. Endothelial NF-kappa B mediates barrier repair by inhibiting endothelial cell (EC) apoptosis. Blockade of endothelial NF-kappa B pathway activated the activator protein (AP)-1 pathway (NF-kappa B-to-AP-1 switch), which compensated for the anti-apoptotic and barrier-repair functions of NF-kappa B. The NF-kappa B-to-AP-1 switch occurred at 24 hours (injury to repair transition phase), but not at 48 hours (repair phase) …

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A Novel Mechanism Of B Cell-Mediated Immune Suppression Through Cd73 Expression And Adenosine Production, H. Kaku, K. F. Cheng, Y. Al-Abed, T. L. Rothstein Jan 2014

A Novel Mechanism Of B Cell-Mediated Immune Suppression Through Cd73 Expression And Adenosine Production, H. Kaku, K. F. Cheng, Y. Al-Abed, T. L. Rothstein

Journal Articles

Immune suppression by regulatory T cells and regulatory B cells is a critical mechanism to limit excess inflammation and autoimmunity. IL-10 is considered the major mediator of B cell induced immune suppression. We report a novel mechanism for immune suppression through adenosine generation by B cells. We identified a novel population of B cells that expresses CD73 as well as CD39, two ectoenzymes that together catalyze the extracellular dephosphorylation of adenine nucleotides to adenosine. Whereas CD39 expression is common among B cells, CD73 expression is not. Approximately 30-50% of B-1 cells (B220(+)CD23(-)) and IL-10 producing B (B10) cells (B220(+)CD5(+)CD1d(hi)) are …

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Pleural Innate Response Activator B Cells Protect Against Pneumonia Via A Gm-Csf-Igm Axis, G. F. Weber, B. G. Chousterman, I. Hilgendorf, C. S. Robbins, I. Theurl, L. M. S. Gerhardt, Y. Iwamoto, T. D. Quach, T. L. Rothstein, F. K. Swirski, +4 Additional Authors Jan 2014

Pleural Innate Response Activator B Cells Protect Against Pneumonia Via A Gm-Csf-Igm Axis, G. F. Weber, B. G. Chousterman, I. Hilgendorf, C. S. Robbins, I. Theurl, L. M. S. Gerhardt, Y. Iwamoto, T. D. Quach, T. L. Rothstein, F. K. Swirski, +4 Additional Authors

Journal Articles

Pneumonia is a major cause of mortality worldwide and a serious problem in critical care medicine, but the immunophysiological processes that confer either protection or morbidity are not completely understood. We show that in response to lung infection, B1a B cells migrate from the pleural space to the lung parenchyma to secrete polyreactive emergency immunoglobulin M ( IgM). The process requires innate response activator (IRA) B cells, a transitional B1a-derived inflammatory subset which controls IgM production via autocrine granulocyte/macrophage colony-stimulating factor (GM-CSF) signaling. The strategic location of these cells, coupled with the capacity to produce GM-CSF-dependent IgM, ensures effective early …

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Recognition Of Antigen-Specific B-Cell Receptors From Chronic Lymphocytic Leukemia Patients By Synthetic Antigen Surrogates, M. Sarkar, Y. Liu, J. Morimoto, H. Peng, C. Aquino, C. Rader, N. Chiorazzi, T. Kodadek Jan 2014

Recognition Of Antigen-Specific B-Cell Receptors From Chronic Lymphocytic Leukemia Patients By Synthetic Antigen Surrogates, M. Sarkar, Y. Liu, J. Morimoto, H. Peng, C. Aquino, C. Rader, N. Chiorazzi, T. Kodadek

Journal Articles

In patients with chronic lymphocytic leukemia (CLL), a single neoplastic antigen-specific B cell accumulates and overgrows other B cells, leading to immune deficiency. CLL is often treated with drugs that ablate all B cells, leading to further weakening of humoral immunity, and a more focused therapeutic strategy capable of targeting only the pathogenic B cells would represent a significant advance. One approach to this would be to develop synthetic surrogates of the CLL antigens allowing differentiation of the CLL cells and healthy B cells in a patient. Here, we describe nonpeptidic molecules capable of targeting antigen-specific B cell receptors with …

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Renin Modulates Hiv Replication In T Cells, N. Chandel, K. Ayasolla, X. Q. Lan, P. Rai, J. Mikulak, M. Husain, A. Malhotra, J. Mcgowan, P. C. Singhal Jan 2014

Renin Modulates Hiv Replication In T Cells, N. Chandel, K. Ayasolla, X. Q. Lan, P. Rai, J. Mikulak, M. Husain, A. Malhotra, J. Mcgowan, P. C. Singhal

Journal Articles

HIV is known to subvert cellular machinery to enhance its replication. Recently, HIV has been reported to enhance TC renin expression. We hypothesized that HIV induces and maintains high renin expression to promote its own replication in TCs. Renin enhanced HIV replication in TCs in a dose-dependent manner. (P)RR-deficient TCs, as well as those lacking renin, displayed attenuated NF-B activity and HIV replication. TCs treated with renin and Hpr displayed activation of the (P)RR-PLZF protein signaling cascade. Renin, HIV, and Hpr activated the PI3K pathway. Both renin and Hpr cleaved Agt (a renin substrate) to Ang I and also cleaved …

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Splenic B-1a Cells Expressing Cd138 Spontaneously Secrete Large Amounts Of Immunoglobulin In Naive Mice, N. E. Holodick, T. Vizconde, T. L. Rothstein Jan 2014

Splenic B-1a Cells Expressing Cd138 Spontaneously Secrete Large Amounts Of Immunoglobulin In Naive Mice, N. E. Holodick, T. Vizconde, T. L. Rothstein

Journal Articles

B-1a cells constitutively secrete natural antibody that provides immediate protection against microbial pathogens and functions homeostatically to speed removal of apoptotic cell debris. Although B-1a cells are especially prominent in the peritoneal and pleural cavities, some B-1a cells reside in the spleen. A small subset of splenic B-1a cells in naive, unimmunized mice express CD138, a recognized plasma cell antigen, whereas the bulk of splenic B-1a cells are CD138 negative. Splenic B-1a cells in toto have been shown to generate much more antibody per cell than peritoneal B-1a cells; however, specific functional information regarding CD138(+) splenic B-1a cells has been …

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Critical Periods Of Increased Fetal Vulnerability To A Maternal High Fat Diet, M. D. Plata, L. Williams, Y. Seki, K. Hartil, H. Kaur, C. L. Lin, A. Fiallo, A. S. Glenn, E. B. Katz, P. M. Vuguin, +2 Additional Authors Jan 2014

Critical Periods Of Increased Fetal Vulnerability To A Maternal High Fat Diet, M. D. Plata, L. Williams, Y. Seki, K. Hartil, H. Kaur, C. L. Lin, A. Fiallo, A. S. Glenn, E. B. Katz, P. M. Vuguin, +2 Additional Authors

Journal Articles

Background: Fetal adaptations to high fat (HF) diet in utero (IU) that may predispose to Metabolic Syndrome (MetS) in adulthood include changes in fetal hepatic gene expression. Studies were performed to determine whether maternal exposure to HF diet at different stages during pregnancy had different effects on the fetus, including hepatic gene expression. Methods: Female wild type mice were fed either a HF or breeding chow (C) for 2 wks prior to mating. The experimental groups were composed of embryonic day (e) 18.5 fetuses obtained from WT female mice that were fed HF (HF, 35.5% fat) or breeding chow (C, …

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