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Article ; Online: Overexpression of methyl-CpG binding protein 2 impairs T(H)1 responses.

Yang, Tianshu / Ramocki, Melissa B / Neul, Jeffrey L / Lu, Wen / Roberts, Luz / Knight, John / Ward, Christopher S / Zoghbi, Huda Y / Kheradmand, Farrah / Corry, David B

Science translational medicine

2012 Volume 4, Issue 163, Page(s) 163ra158

Abstract: ... helper cell type 2 (T(H)2)-dependent allergic responses. Relative to normal T cells, T(H) cells from children ... and mice with MECP2 duplication displayed similar impairments in IFN-γ secretion and T(H)1 responses ... suppresses IFN-γ secretion from T(H) cells, potentially leading to a partially immunodeficient state ...

Abstract	The DNA binding protein methyl-CpG binding protein 2 (MeCP2) critically influences neuronal and brain function by modulating gene expression, and children with overexpression of the MECP2 gene exhibit postnatal neurological syndromes. We demonstrate that some children with MECP2 duplication also display variable immunological abnormalities that include reductions in memory T and B cells and natural killer cells and immunoglobulin assay responses. Moreover, whereas mice with MeCP2 overexpression were unable to control infection with the intra-macrophage parasite Leishmania major and secrete interferon-γ (IFN-γ) from involved lymph nodes, they were able to control airway fungal infection by Aspergillus niger and mount protective T helper cell type 2 (T(H)2)-dependent allergic responses. Relative to normal T cells, T(H) cells from children and mice with MECP2 duplication displayed similar impairments in IFN-γ secretion and T(H)1 responses that were due to both MeCP2-dependent suppression of IFN-γ transcription and sequestration of the IFN-γ locus as assessed by chromatin immunoprecipitation assay. Thus, overexpressed MeCP2 aberrantly suppresses IFN-γ secretion from T(H) cells, potentially leading to a partially immunodeficient state. Our findings establish a rational basis for identifying, treating, and preventing infectious complications potentially affecting children with MECP2 duplication.
MeSH term(s)	Animals ; Cell Differentiation/genetics ; Cell Differentiation/physiology ; Cells, Cultured ; Chromatin Immunoprecipitation ; Flow Cytometry ; Gene Duplication/genetics ; Gene Duplication/physiology ; Humans ; Interferon-gamma/metabolism ; Leishmania major/pathogenicity ; Leishmaniasis, Cutaneous/immunology ; Methyl-CpG-Binding Protein 2/genetics ; Methyl-CpG-Binding Protein 2/metabolism ; Mice ; RNA, Small Interfering ; Th1 Cells/immunology ; Th1 Cells/metabolism
Chemical Substances	Methyl-CpG-Binding Protein 2 ; RNA, Small Interfering ; Interferon-gamma (82115-62-6)
Language	English
Publishing date	2012-12-07
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2518854-9
ISSN	1946-6242 ; 1946-6234
ISSN (online)	1946-6242
ISSN	1946-6234
DOI	10.1126/scitranslmed.3004430
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Article: Detection of autoreactive T cells in H-2u mice using peptide-MHC multimers.

Radu, C G / Anderton, S M / Firan, M / Wraith, D C / Ward, E S

International immunology

2000 Volume 12, Issue 11, Page(s) 1553–1560

Abstract: ... of experimental autoimmune encephalomyelitis (EAE), a prototype for T cell-mediated autoimmunity. In PL/J and B10.PL mice (H-2(u) haplotype ... MHC class II tetramers, that 15,000-70,000 self-antigen-specific T(h) cells accumulate in the draining ... Myelin basic protein (MBP)-specific T cells play a critical role in the pathogenesis ...

Abstract	Myelin basic protein (MBP)-specific T cells play a critical role in the pathogenesis of experimental autoimmune encephalomyelitis (EAE), a prototype for T cell-mediated autoimmunity. In PL/J and B10.PL mice (H-2(u) haplotype), the immunodominant epitope of MBP is represented by an N-terminal nonameric peptide, MBP1-9. To date, the MBP1-9-specific T cell repertoire has not been analyzed in quantitative terms. In the present study we demonstrate, using MHC class II tetramers, that 15,000-70,000 self-antigen-specific T(h) cells accumulate in the draining lymph nodes following immunization with spinal cord homogenate or MBP1-9. In contrast, MBP1-9-specific T cells are undetectable in unimmunized H-2(u) mice and represent >60% of the CD4 cells in naive mice transgenic for a TCR specific for this epitope. The results suggest that the extremely low affinity of the N-terminal peptide for I-A(u) does not limit the MBP1-9-specific T cells from expanding into a sizeable pool of autoreactive T cells. Therefore, the primary immune response to MBP1-9 does not differ quantitatively from previously reported CD4(+) T cell responses to foreign antigens.
MeSH term(s)	Animals ; Autoantigens/administration & dosage ; Autoantigens/immunology ; Epitopes, T-Lymphocyte/biosynthesis ; Epitopes, T-Lymphocyte/immunology ; Freund's Adjuvant/immunology ; H-2 Antigens/biosynthesis ; H-2 Antigens/immunology ; Histocompatibility Antigens Class II/biosynthesis ; Histocompatibility Antigens Class II/chemistry ; Histocompatibility Antigens Class II/immunology ; Hybridomas ; Injections, Subcutaneous ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Myelin Basic Protein/administration & dosage ; Myelin Basic Protein/immunology ; Peptide Fragments/administration & dosage ; Peptide Fragments/biosynthesis ; Peptide Fragments/immunology ; Receptors, Antigen, T-Cell, alpha-beta/biosynthesis ; T-Lymphocytes/immunology
Chemical Substances	Autoantigens ; Epitopes, T-Lymphocyte ; H-2 Antigens ; Histocompatibility Antigens Class II ; Myelin Basic Protein ; Peptide Fragments ; Receptors, Antigen, T-Cell, alpha-beta ; T-cell receptor Vbeta 8.2 ; myelin basic protein 1-9 ; myelin basic protein Ac1-11(4Y) ; Freund's Adjuvant (9007-81-2)
Language	English
Publishing date	2000-11
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	1013745-2
ISSN	1460-2377 ; 0953-8178
ISSN (online)	1460-2377
ISSN	0953-8178
DOI	10.1093/intimm/12.11.1553
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Zs.A 2619: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Metric Engineering of Crystalline Inclusion Compounds by Structural Mimicry This work was supported in part by the MRSEC Program of the National Science Foundation (Award Number DMR-9809364) and by the Natural Sciences and Engineering Research Council of Canada (postdoctoral fellowship for K.T.H.).

Holman / Ward

Angewandte Chemie (International ed. in English)

2000 Volume 39, Issue 9, Page(s) 1653–1656

Language	English
Publishing date	2000-05
Publishing country	Germany
Document type	Journal Article
ZDB-ID	2011836-3
ISSN	1521-3773 ; 1433-7851
ISSN (online)	1521-3773
ISSN	1433-7851
DOI	10.1002/(sici)1521-3773(20000502)39:9<1653::aid-anie1653>3.0.co;2-7
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Article ; Online: Lamellae-Nanotube Isomerism in Hydrogen-Bonded Host Frameworks This work was supported by the National Science Foundation (DMR-9908627), in part by the MRSEC Program of the National Science Foundation (DMR-9809364), and the Natural Sciences and Engineering Research Council of Canada (postdoctoral fellowship for K.T.H.).

Horner, Matthew J. / Holman, K. Travis / Ward, Michael D.

Angewandte Chemie (International ed. in English)

2001 Volume 40, Issue 21, Page(s) 4045–4048

Language	English
Publishing date	2001-11-05
Publishing country	Germany
Document type	Journal Article
ZDB-ID	2011836-3
ISSN	1521-3773 ; 1433-7851
ISSN (online)	1521-3773
ISSN	1433-7851
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Article ; Online: The Modern History of Alcohol Research: Introducing the Rutgers Digital Alcohol Studies Archives.

Ward, J H / Babor, T F / Allred, N / Bejarano, W

Journal of studies on alcohol and drugs

2024

Language	English
Publishing date	2024-01-25
Publishing country	United States
Document type	Journal Article
ZDB-ID	2266450-6
ISSN	1938-4114 ; 1934-2683 ; 1937-1888 ; 0096-882X
ISSN (online)	1938-4114 ; 1934-2683
ISSN	1937-1888 ; 0096-882X
DOI	10.15288/jsad.23-00353
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Un I Zs.547: Show issues

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Conference proceedings ; Online: The role of spatial dependence in global-scale coastal flood risk assessment

Li, H. / Haer, T. / Enríquez, A. / Ward, P.

XXVIII General Assembly of the International Union of Geodesy and Geophysics (IUGG)

2023

Abstract: Coastal flooding is among the world’s deadliest and costliest natural hazards. Its impacts can be particularly high when an event affects a large spatial area. Current large-scale flood risk studies assume that the probabilities of water levels during ... ...

Abstract	Coastal flooding is among the world’s deadliest and costliest natural hazards. Its impacts can be particularly high when an event affects a large spatial area. Current large-scale flood risk studies assume that the probabilities of water levels during such events do not vary in space. This failure to capture flood spatial dependence can lead to large misestimates of the hazard and associated risk, and therefore potentially misinform the risk management community. In this contribution, we assess the effects of spatial dependence on coastal flood risk estimation at the global scale. To this end, we compare the assessments using two spatial dependence scenarios: 1) complete dependence and 2) modelled dependence of water level return periods. For the first scenario, we use the existing risk information calculated by the GLOFRIS global risk modelling framework. To estimate the spatially-dependent risks, we use an event-based approach and consider 10,000-year extreme coastal flood events from the global synthetic dataset of spatially-dependent extreme sea levels. These spatially-coherent return periods are then combined with the GLOFRIS spatially-constant inundation layers to create the spatially-dependent inundation map. These maps are further overlaid with exposure layers and vulnerability information to assess the coastal flood impacts. The flood risk is estimated empirically and presented in terms of expected annual population and expected annual damage. This study will provide improved risk estimation at the global scale, which could be used to enhance flood risk management through better wide-area planning decisions, more accurate insurance coverage, and better emergency response.
Subject code	910
Language	English
Publishing country	de
Document type	Conference proceedings ; Online
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Article ; Online: Genetic background and sex influence somatosensory sensitivity and oxycodone analgesia in the Hybrid Rat Diversity Panel.

Duffy, Eamonn P / Ward, J O / Hale, L H / Brown, K T / Kwilasz, Andrew J / Saba, Laura M / Ehringer, Marissa A / Bachtell, Ryan K

Genes, brain, and behavior

2024 Volume 23, Issue 2, Page(s) e12894

Abstract: ... over the course of 2 h. Both mechanical and thermal sensitivity are shaped by genetic factors and ... display moderate heritability (h ...

Abstract	Opioid use disorder (OUD) is an ongoing public health concern in the United States, and relatively little work has addressed how genetic background contributes to OUD. Understanding the genetic contributions to oxycodone-induced analgesia could provide insight into the early stages of OUD development. Here, we present findings from a behavioral phenotyping protocol using several inbred strains from the Hybrid Rat Diversity Panel. Our behavioral protocol included a modified "up-down" von Frey procedure to measure inherent strain differences in the sensitivity to a mechanical stimulus on the hindpaw. We also performed the tail immersion assay, which measures the latency to display tail withdrawal in response to a hot water bath. Initial withdrawal thresholds were taken in drug-naïve animals to record baseline thermal sensitivity across the strains. Oxycodone-induced analgesia was measured after administration of oxycodone over the course of 2 h. Both mechanical and thermal sensitivity are shaped by genetic factors and display moderate heritability (h
MeSH term(s)	Rats ; Animals ; Oxycodone/pharmacology ; Analgesics, Opioid/pharmacology ; Analgesia ; Opioid-Related Disorders
Chemical Substances	Oxycodone (CD35PMG570) ; Analgesics, Opioid
Language	English
Publishing date	2024-04-10
Publishing country	England
Document type	Journal Article
ZDB-ID	2075819-4
ISSN	1601-183X ; 1601-1848
ISSN (online)	1601-183X
ISSN	1601-1848
DOI	10.1111/gbb.12894
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Zs.A 5642: Show issues

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Article ; Online: Patients Who Have Limited English Proficiency Have Decreased Utilization of Revision Surgeries After Hip and Knee Arthroplasty.

Nguyen, Kevin H / Suarez, Pablo / Sales, Chloe / Fernandez, Alicia / Ward, Derek T / Manuel, Solmaz P

The Journal of arthroplasty

2023 Volume 38, Issue 8, Page(s) 1429–1433

Abstract: Background: While racial and ethnic disparities are well documented in access to total joint arthroplasty (TJA), little is known about the association between having limited English proficiency (LEP) and postoperative care access. This study seeks to ... ...

Abstract	Background: While racial and ethnic disparities are well documented in access to total joint arthroplasty (TJA), little is known about the association between having limited English proficiency (LEP) and postoperative care access. This study seeks to correlate LEP status with rates of revision surgery after hip and knee arthroplasty. Methods: This was a retrospective cohort study of patients aged ≥ 18 years who underwent either total hip or total knee arthroplasty between January 2013 and December 2021 at a single academic medical center. The predictor variable was English proficiency status, where LEP was defined as having a primary language that was not English. Multivariable regressions controlling for potential demographic and clinical confounders were used to calculate adjusted odds ratios of undergoing revision surgery within 1 and 2 years after primary arthroplasty for patients who have LEP, compared to English proficient patients. Results: A total of 7,985 hip and knee arthroplasty surgeries were included in the analysis. There were 577 (7.2%) patients who were classified as having LEP. Patients who have LEP were less likely to undergo revision surgeries within 1 year (1.4% versus 3.2%, P = .01) and 2 years (1.7% versus 3.9%, P = .006) of primary TJA. Patients who have LEP had adjusted odds ratios of 0.45 (confidence interval: 0.22-0.92, P = .03) and 0.44 (confidence interval: 0.23-0.85, P = .01) of receiving revision surgery within 1 and 2 years, respectively. Conclusion: Patients who have LEP, compared to English proficient patients, were less likely to undergo revision surgeries at the same institution up to 2 years after hip and knee arthroplasty. These findings suggest that patients who have LEP may face barriers in accessing postoperative care.
MeSH term(s)	Humans ; Arthroplasty, Replacement, Knee ; Limited English Proficiency ; Reoperation ; Retrospective Studies ; Surveys and Questionnaires
Language	English
Publishing date	2023-02-18
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	632770-9
ISSN	1532-8406 ; 0883-5403
ISSN (online)	1532-8406
ISSN	0883-5403
DOI	10.1016/j.arth.2023.02.024
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Zs.A 2134: Show issues

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Article ; Online: Language barriers and postoperative opioid prescription use after total knee arthroplasty.

Nguyen, Kevin H / Rambachan, Aksharananda / Ward, Derek T / Manuel, Solmaz P

Exploratory research in clinical and social pharmacy

2022 Volume 7, Page(s) 100171

Abstract: Background: Patients with limited English proficiency (LEP) face difficulties in access to postoperative follow-up care, including post-discharge medication refills. However, prior studies have not examined how utilization of prescription pain ... ...

Abstract	Background: Patients with limited English proficiency (LEP) face difficulties in access to postoperative follow-up care, including post-discharge medication refills. However, prior studies have not examined how utilization of prescription pain medications after discharge from joint replacement surgeries differs between English proficient (EP) and LEP patients. Objective: This study explored the relationship between English language proficiency and opioid prescription refill requests after hospital discharge for total knee arthroplasty (TKA). Methods: This was an observational cohort study of patients ≥18 years of age who underwent TKA between January 2015 and December 2019 at a single academic center. LEP status was defined as not having English as the primary language and requesting an interpreter. Primary outcome variables included opioid pain medication refill requests between 0 and 90 days from discharge. Multivariable logistic regression modeling calculated the odds ratios of requesting an opioid refill. Results: A total of 2148 patients underwent TKA, and 9.8% had LEP. Postoperative pain levels and rates of prior opioid use did not differ between LEP and EP patients. LEP patients were less likely to request an opioid prescription refill within 30 days (35.3% vs 52.4%, p < 0.001), 60 days (48.7% vs 61.0%, p = 0.004), and 90 days (54.0% vs 62.9%, p = 0.041) after discharge. In multivariable analysis, LEP patients had an odds ratio of 0.61 of requesting an opioid refill (95% CI, 0.41-0.92, p = 0.019) within 30 days of discharge. Having Medicare insurance and longer lengths of hospitalization were correlated with lower odds of 0-30 days opioid refills, while prior opioid use and being discharged home were associated with higher odds of opioid refill requests 0-30 days after discharge for TKA. Conclusions: Language barriers may contribute to poorer access to postoperative care, including prescription medication refills. Barriers to postoperative care may exist at multiple levels for LEP patients undergoing surgical procedures.
Language	English
Publishing date	2022-08-23
Publishing country	United States
Document type	Journal Article
ISSN	2667-2766
ISSN (online)	2667-2766
DOI	10.1016/j.rcsop.2022.100171
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Article ; Online: The iso-oncotopic response: immunotherapy-associated bullous pemphigoid in tumour footprints.

Pearlman, Ross / Badon, Hannah / Whittington, Andrew / Brodell, Robert T / Ward, Kimberley H M

Clinical and experimental dermatology

2022 Volume 47, Issue 7, Page(s) 1379–1381

Abstract: This case report describes a unique distribution of bullous pemphigoid induced by cemiplimab therapy. The patient preferentially developed bullae in the scar "footprints" of previous non-melanoma skin cancers, yet traumatic scars were spared. We propose ... ...

Abstract	This case report describes a unique distribution of bullous pemphigoid induced by cemiplimab therapy. The patient preferentially developed bullae in the scar "footprints" of previous non-melanoma skin cancers, yet traumatic scars were spared. We propose to describe this distribution as an 'iso-oncotopic response'.
MeSH term(s)	Humans ; Immunologic Factors ; Immunotherapy/adverse effects ; Neoplasms ; Pemphigoid, Bullous/chemically induced ; Pemphigoid, Bullous/drug therapy
Chemical Substances	Immunologic Factors
Language	English
Publishing date	2022-05-14
Publishing country	England
Document type	Case Reports ; Letter
ZDB-ID	195504-4
ISSN	1365-2230 ; 0307-6938
ISSN (online)	1365-2230
ISSN	0307-6938
DOI	10.1111/ced.15177
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