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Articles 271 - 300 of 409

Full-Text Articles in Allergy and Immunology

Establishing 3d Endometrial Organoids From The Mouse Uterus, Suni Tang, Sydney E Parks, Zian Liao, Dominique I Cope, Sarah E Blutt, Diana Monsivais Jan 2023

Establishing 3d Endometrial Organoids From The Mouse Uterus, Suni Tang, Sydney E Parks, Zian Liao, Dominique I Cope, Sarah E Blutt, Diana Monsivais

Faculty, Staff and Students Publications

Endometrial tissue lines the inner cavity of the uterus and is under the cyclical control of estrogen and progesterone. It is a tissue that is composed of luminal and glandular epithelium, a stromal compartment, a vascular network, and a complex immune cell population. Mouse models have been a powerful tool to study the endometrium, revealing critical mechanisms that control implantation, placentation, and cancer. The recent development of 3D endometrial organoid cultures presents a state-of-the-art model to dissect the signaling pathways that underlie endometrial biology. Establishing endometrial organoids from genetically engineered mouse models, analyzing their transcriptomes, and visualizing their morphology at …


Increased Camkk2 Expression Is An Adaptive Response That Maintains The Fitness Of Tumor-Infiltrating Natural Killer Cells, Patrick K Juras, Luigi Racioppi, Debarati Mukherjee, Sandeep Artham, Xia Gao, Laura Akullian D'Agostino, Ching-Yi Chang, Donald P Mcdonnell Jan 2023

Increased Camkk2 Expression Is An Adaptive Response That Maintains The Fitness Of Tumor-Infiltrating Natural Killer Cells, Patrick K Juras, Luigi Racioppi, Debarati Mukherjee, Sandeep Artham, Xia Gao, Laura Akullian D'Agostino, Ching-Yi Chang, Donald P Mcdonnell

Faculty, Staff and Students Publications

Calcium/calmodulin-dependent protein kinase kinase 2 (CaMKK2) is a key regulator of energy homeostasis in several cell types. Expression of this enzyme in tumor cells promotes proliferation and migration, and expression in tumor-associated immune cells facilitates M2 macrophage polarization and the development of myeloid-derived suppressor cells. Thus, there has been interest in developing CaMKK2 inhibitors as potential anticancer therapeutics. One impediment to clinical development of these agents is that the roles of CaMKK2 in other cellular compartments within the tumor immune microenvironment remain to be established. We report herein that CaMKK2 is expressed at low basal levels in natural killer (NK) …


Leukocytes As Mediators Of Gut-Brain Communication, Dilini Ekanayake Jan 2023

Leukocytes As Mediators Of Gut-Brain Communication, Dilini Ekanayake

Biomedical Sciences Posters and Presentations

Food allergies

▪ Reactions range from mild/delayed to severe/rapid. ▪ People with mild allergic reactions have increased re-exposure risks. ▪ Cow’s milk allergy tends to manifest with milder allergic reactions.

Cow’s milk allergy (CMA)

▪ CMA has been associated with behavioral and neurological disorders. ▪ How allergic inflammatory signals from the gut reach the brain is unclear


Continuous Consumption Of Whey Protein Affects Motor And Cognitive Functions In A Mouse Model Of Cow’S Milk Hypersensitivity, Geetika Verma Jan 2023

Continuous Consumption Of Whey Protein Affects Motor And Cognitive Functions In A Mouse Model Of Cow’S Milk Hypersensitivity, Geetika Verma

Biomedical Sciences Posters and Presentations

Hypersensitization to a food allergen can occur in the absence of immediate allergic reactions, a condition referred to as asymptomatic sensitization. Using mice asymptomatically sensitized to a bovine whey allergen, β-lactoglobulin (BLG, Bos d 5), we have previously shown that chronic exposure to the allergen results in behavior changes with increased neuroinflammation and cortical demyelination. However, whether allergen avoidance can resolve these pathologies is unknown. Thus, we aimed to compare immunological and behavioral changes in sham- or BLG-sensitized mice with or without the removal of dietary whey after the mice had consumed either a control diet (CTL) or a whey-protein-containing …


Continued Food-Allergen Consumption Exacerbates Beta-Amyloid Accumulation In Allergen-Sensitized Appnl-G-Fmice., Afrina Brishti Jan 2023

Continued Food-Allergen Consumption Exacerbates Beta-Amyloid Accumulation In Allergen-Sensitized Appnl-G-Fmice., Afrina Brishti

Biomedical Sciences Posters and Presentations

Alzheimer’s disease (AD) is the most common neurodegenerative disease, with β-amyloid(Aβ) plaque deposition being one of the hallmark pathologies. However, the etiology of AD remains elusive. While chronic inflammation from recurrent infections or injury seems to contribute to AD development, it is unclear whether atopic diseases, such as allergies, are associated with AD. We previously reported that continuous consumption of a whey protein(WP) -containing diet led to lasting neuro inflammation in C57BL/6J mice that were sensitized but tolerant to a bovine milk allergen, β-lactoglobulin (BLG;Bosd5). Thus, we hypothesized that the persisting neuroinflammation due to repeated allergen consumption would exacerbate AD …


Histamine H3 Receptor Antagonism Mitigates Food-Hypersensitivity-Associated Depressive Behavior And Neuropathology In A Mouse Model Of Cow’S Milk Allergy, Danielle Germundson-Hermanson Jan 2023

Histamine H3 Receptor Antagonism Mitigates Food-Hypersensitivity-Associated Depressive Behavior And Neuropathology In A Mouse Model Of Cow’S Milk Allergy, Danielle Germundson-Hermanson

Biomedical Sciences Posters and Presentations

Background Histamine is best known for causing allergy symptoms, but it also regulates blood-brain barrier permeability1 and oligodendrocyte differentiation2. Thus, brain histamine levels are tightly controlled.

Previous Findings We demonstrated that histamine and histamine H3 receptor (H3R) levels were elevated in a mouse model of cow’s milk allergy (CMA) in association with intracranial mast cell activation, depression-like behaviors, and cortical demyelination3,4.

Gaps in Knowledge In humans, food allergies are often associated with neuropsychiatric disorders5-7, but the involvement of allergy induced histamine in triggering behavioral changes is unclear.

Hypothesis Repeated allergen consumption can lead to central histaminergic dysfunction through H3R, ultimately …


Continuous Consumption Of Whey Protein Maintains Neuroinflammation In A Mouse Model Of Asymptomatic Cow’S Milk Allergy, Geetika Verma Jan 2023

Continuous Consumption Of Whey Protein Maintains Neuroinflammation In A Mouse Model Of Asymptomatic Cow’S Milk Allergy, Geetika Verma

Biomedical Sciences Posters and Presentations

Using a mouse model of cow’s milk allergy (CMA), we previously showed that C57BL/6J mice sensitized to a bovine whey allergen, β-lactoglobulin (BLG), exhibited anxiety/depression-like behavior and neuroinflammation in the absence of overt anaphylaxis upon allergen exposure


Milk Allergen Increases Intestinal Immune Cells In Association With Neuroinflammation And Behavioral Changes, Dilini Ekanayake Jan 2023

Milk Allergen Increases Intestinal Immune Cells In Association With Neuroinflammation And Behavioral Changes, Dilini Ekanayake

Biomedical Sciences Posters and Presentations

Cow’s milk allergy (CMA)

 CMA h as been associated with neurological disorders.

 How allergic inflammatory signals from the gut reach the brain is unclear.


Repeated Allergen Exposure Induces Histaminergic Dysregulation And Depression-Like Behaviors In A Non-Anaphylactic Food Allergy Mouse Model, Danielle Germundson-Hermanson Jan 2023

Repeated Allergen Exposure Induces Histaminergic Dysregulation And Depression-Like Behaviors In A Non-Anaphylactic Food Allergy Mouse Model, Danielle Germundson-Hermanson

Biomedical Sciences Posters and Presentations

▪ Food allergy is often comorbid with neuropsychiatric disorders such as anxiety1,2, depression1,2, OCD3, ADD/ADHD4, and autism5. ➢ The mechanism of how food allergy may impact brain function and behavior in certain allergic individuals has yet to be elucidated.

▪ Mast cells (MCs) are not only the effector cell of the hypersensitivity response but are also important in maintaining brain homeostasis6. ➢ MCs have been implicated in neuropsychiatric and neurodegenerative disorders such as multiple sclerosis7,8.

▪ We have previously found in a mouse model of cow’s milk allergy (CMA) that intracranial MC numbers9 and histamine 3 receptor (H3R)10 increased after …


Cortical Demyelination And Depression-Like Behavior Are Associated With Histaminergic Dysregulation In A Mouse Model Of Peripheral Inflammation, Danielle Germundson-Hermanson Jan 2023

Cortical Demyelination And Depression-Like Behavior Are Associated With Histaminergic Dysregulation In A Mouse Model Of Peripheral Inflammation, Danielle Germundson-Hermanson

Biomedical Sciences Posters and Presentations

▪ Demyelinating diseases of the central nervous system are increasing in prevalence world-wide1,2 and manifest as motor, behavioral, and/or cognitive defects3 . The etiology and pathophysiology of demyelinating diseases remain unclear.

▪ We have previously observed cortical demyelination in our mouse model of non-anaphylactic cow’s milk allergy4 . The demyelination was associated with depression-like behaviors and region-specific increases in brain histamine and H3 receptor (H3R) levels4,5 .

❖ The brain’s central histaminergic system is tightly controlled and regulates many behaviors. Additionally, signaling through H3R plays a crucial role in oligodendrocyte differentiation, and thus, demyelination and remyelination6 .

▪ We hypothesized …


Dietary Whey Protein Increases Brain Leukocytes In Mice Regardless Of Their Hypersensitivity Status, Dilini Ekanayake Jan 2023

Dietary Whey Protein Increases Brain Leukocytes In Mice Regardless Of Their Hypersensitivity Status, Dilini Ekanayake

Biomedical Sciences Posters and Presentations

Cow’s milk allergy (CMA) often manifests as milder reactions and may be linked to neurological problems. Previously, we demonstrated that C57BL/6J mice sensitized to a bovine whey allergen, β-lactoglobulin (BLG, Bos d 5), moderately increased BLG-specific IgE levels and exhibited behavioral changes without severe allergic reactions. When these non-anaphylactic CMA mice were placed on a whey-protein (WP)-containing diet for 2 weeks to simulate continuous dairy consumption, we found neuropathology indicative of neuroinflammation and cortical demyelination. Since immune cells migrate to the central nervous system (CNS) and promote neuroinflammation in demyelinating conditions such as multiple sclerosis, we hypothesized that the number …


Investigating The Potential Role Of Akkermansia Muciniphila Supplementation In Neuroinflammation: A Progress Report, Geetika Verma Jan 2023

Investigating The Potential Role Of Akkermansia Muciniphila Supplementation In Neuroinflammation: A Progress Report, Geetika Verma

Biomedical Sciences Posters and Presentations

Gut bacteria are important for proper development and function of the host immune system (1). Recent studies have provided association of altered microbiome in both food allergy and neuropsychiatric disorders (2, 3) indicating potential role of microbiome in regulating Gut-Brain-Axis. Akkermansia muciniphila belongs to the phylum Verrucomicrobia, is a commensal mucin degrading bacterial species (4). A. muciniphila protects the gut barrier by facilitating host mucus production. Since patients with food allergy have increased gut permeability, protection of intestinal barrier by increased mucus production may be beneficial in preventing allergen and pathogen infiltrations, hence, minimizing inflammation. A. muciniphila is well known …


Naproxen Chemoprevention Induces Proliferation Of Cytotoxic Lymphocytes In Lynch Syndrome Colorectal Mucosa, Charles M Bowen, Nan Deng, Laura Reyes-Uribe, Edwin Roger Parra, Pedro Rocha, Luisa M Solis, Ignacio I Wistuba, Valerie O Sepeda, Lana Vornik, Marjorie Perloff, Eva Szabo, Asad Umar, Krishna M Sinha, Powel H Brown, Eduardo Vilar Jan 2023

Naproxen Chemoprevention Induces Proliferation Of Cytotoxic Lymphocytes In Lynch Syndrome Colorectal Mucosa, Charles M Bowen, Nan Deng, Laura Reyes-Uribe, Edwin Roger Parra, Pedro Rocha, Luisa M Solis, Ignacio I Wistuba, Valerie O Sepeda, Lana Vornik, Marjorie Perloff, Eva Szabo, Asad Umar, Krishna M Sinha, Powel H Brown, Eduardo Vilar

Faculty, Staff and Student Publications

BACKGROUND: Recent clinical trial data from Lynch Syndrome (LS) carriers demonstrated that naproxen administered for 6-months is a safe primary chemoprevention that promotes activation of different resident immune cell types without increasing lymphoid cellularity. While intriguing, the precise immune cell types enriched by naproxen remained unanswered. Here, we have utilized cutting-edge technology to elucidate the immune cell types activated by naproxen in mucosal tissue of LS patients.

METHODS: Normal colorectal mucosa samples (pre- and post-treatment) from a subset of patients enrolled in the randomized and placebo-controlled 'Naproxen Study' were obtained and subjected to a tissue microarray for image mass cytometry …


Distinct Patterns Of Auto-Reactive Antibodies Associated With Organ-Specific Immune-Related Adverse Events, Mehmet Altan, Quan-Zhen Li, Qi Wang, Natalie I Vokes, Ajay Sheshadri, Jianjun Gao, Chengsong Zhu, Hai T Tran, Saumil Gandhi, Mara B Antonoff, Stephen Swisher, Jing Wang, Lauren A Byers, Noha Abdel-Wahab, Maria C Franco-Vega, Yinghong Wang, J Jack Lee, Jianjun Zhang, John V Heymach Jan 2023

Distinct Patterns Of Auto-Reactive Antibodies Associated With Organ-Specific Immune-Related Adverse Events, Mehmet Altan, Quan-Zhen Li, Qi Wang, Natalie I Vokes, Ajay Sheshadri, Jianjun Gao, Chengsong Zhu, Hai T Tran, Saumil Gandhi, Mara B Antonoff, Stephen Swisher, Jing Wang, Lauren A Byers, Noha Abdel-Wahab, Maria C Franco-Vega, Yinghong Wang, J Jack Lee, Jianjun Zhang, John V Heymach

Faculty, Staff and Student Publications

UNLABELLED: The roles of preexisting auto-reactive antibodies in immune-related adverse events (irAEs) associated with immune checkpoint inhibitor therapy are not well defined. Here, we analyzed plasma samples longitudinally collected at predefined time points and at the time of irAEs from 58 patients with immunotherapy naïve metastatic non-small cell lung cancer treated on clinical protocol with ipilimumab and nivolumab. We used a proteomic microarray system capable of assaying antibody reactivity for IgG and IgM fractions against 120 antigens for systemically evaluating the correlations between auto-reactive antibodies and certain organ-specific irAEs. We found that distinct patterns of auto-reactive antibodies at baseline were …


Pyrolyzed Deketene Curcumin Controls Regulatory T Cell Generation And Gastric Cancer Metabolism Cooperate With 2-Deoxy-D-Glucose, Takashi Maruyama, Hirofumi Miyazaki, Yun-Ji Lim, Jian Gu, Masaki Ishikawa, Taichi Yoshida, Wanjun Chen, Yuji Owada, Hiroyuki Shibata Jan 2023

Pyrolyzed Deketene Curcumin Controls Regulatory T Cell Generation And Gastric Cancer Metabolism Cooperate With 2-Deoxy-D-Glucose, Takashi Maruyama, Hirofumi Miyazaki, Yun-Ji Lim, Jian Gu, Masaki Ishikawa, Taichi Yoshida, Wanjun Chen, Yuji Owada, Hiroyuki Shibata

Faculty, Staff and Student Publications

Pyrolyzed deketene curcumin GO-Y022 prevents carcinogenesis in a gastric cancer mouse model. However, it is still less clear if GO-Y022 affects tumor-induced immune suppression. In this study, we found that GO-Y022 inhibited Treg generation in the presence of transforming growth factor beta 1 (TGF-β). However, GO-Y022 showed less impact on Foxp3+ Tregs in the gastric tumor microenvironment. Gastric tumor cells produce a large amount of L-lactate in the presence of GO-Y022 and diminish the inhibitory role of GO-Y022 against Treg generation in response to TGF-β. Therefore, naïve CD4+ T cells co-cultured with GO-Y022 treated gastric tumor cells increased Treg generation. …


Spatial Modelling Of The Tumor Microenvironment From Multiplex Immunofluorescence Images: Methods And Applications, Gayatri Kumar, Renganayaki Krishna Pandurengan, Edwin Roger Parra, Kasthuri Kannan, Cara Haymaker Jan 2023

Spatial Modelling Of The Tumor Microenvironment From Multiplex Immunofluorescence Images: Methods And Applications, Gayatri Kumar, Renganayaki Krishna Pandurengan, Edwin Roger Parra, Kasthuri Kannan, Cara Haymaker

Faculty, Staff and Student Publications

Spatial modelling methods have gained prominence with developments in high throughput imaging platforms. Multiplex immunofluorescence (mIF) provides the scope to examine interactions between tumor and immune compartment at single cell resolution using a panel of antibodies that can be chosen based on the cancer type or the clinical interest of the study. The markers can be used to identify the phenotypes and to examine cellular interactions at global and local scales. Several translational studies rely on key understanding of the tumor microenvironment (TME) to identify drivers of immune response in immunotherapy based clinical trials. To improve the success of ongoing …


Blockade Of Mglur5 In Astrocytes Derived From Human Ipscs Modulates Astrocytic Function And Increases Phagocytosis, Izabella B Q De Lima, Pablo L Cardozo, Julia S Fahel, Juliana P S Lacerda, Aline S Miranda, Antônio L Teixeira, Fabiola M Ribeiro Jan 2023

Blockade Of Mglur5 In Astrocytes Derived From Human Ipscs Modulates Astrocytic Function And Increases Phagocytosis, Izabella B Q De Lima, Pablo L Cardozo, Julia S Fahel, Juliana P S Lacerda, Aline S Miranda, Antônio L Teixeira, Fabiola M Ribeiro

Faculty, Staff and Student Publications

TNF-α is essential for induction and maintenance of inflammatory responses and its dysregulation is associated with susceptibility to various pathogens that infect the central nervous system. Activation of both microglia and astrocytes leads to TNF-α production, which in turn triggers further activation of these cells. Astrocytes have been implicated in the pathophysiology of a wide range of neurodegenerative diseases with either harmful or protective roles, as these cells are capable of secreting several inflammatory factors and also promote synapse elimination and remodeling. These responses are possible because they sense their surroundings via several receptors, including the metabotropic glutamate receptor 5 …


Development And Validation Of Early Death Risk Score Model For Emergency Status Prediction In Very Severe Aplastic Anemia, Xu Liu, Wenrui Yang, Li Zhang, Liping Jing, Lei Ye, Kang Zhou, Yuan Li, Jianping Li, Huihui Fan, Yang Yang, Youzhen Xiong, Xin Zhao, Fengkui Zhang Jan 2023

Development And Validation Of Early Death Risk Score Model For Emergency Status Prediction In Very Severe Aplastic Anemia, Xu Liu, Wenrui Yang, Li Zhang, Liping Jing, Lei Ye, Kang Zhou, Yuan Li, Jianping Li, Huihui Fan, Yang Yang, Youzhen Xiong, Xin Zhao, Fengkui Zhang

Faculty, Staff and Student Publications

This study developed and validated the Early Death Risk Score Model for early identification of emergency patients with very severe aplastic anemia (VSAA). All 377 patients with VSAA receiving first-line immunosuppressive therapy (IST) were categorized into training (n=252) and validation (n=125) cohorts. In the training cohort, age >24 years, absolute neutrophil count ≤0.015×109/L, serum ferritin >900ng/mL and times of fever before IST >1 time were significantly associated with early death. Covariates were assigned scores and categorized as: low (score 0-4), medium (score 5-7) and high (score ≥8) risk. Early death rate was significantly different between risk groups and the validation …


Protective Role Of Colitis In Inflammatory Arthritis Via Propionate-Producing Bacteroides In The Gut, Hoh-Jeong Shon, Yu-Mi Kim, Kyeong Seog Kim, Jin-Ouk Choi, Sang-Hyun Cho, Sujin An, Se-Hyeon Park, Yong-Joon Cho, Joo-Hong Park, Sang-Uk Seo, Joo-Youn Cho, Wan-Uk Kim, Donghyun Kim Jan 2023

Protective Role Of Colitis In Inflammatory Arthritis Via Propionate-Producing Bacteroides In The Gut, Hoh-Jeong Shon, Yu-Mi Kim, Kyeong Seog Kim, Jin-Ouk Choi, Sang-Hyun Cho, Sujin An, Se-Hyeon Park, Yong-Joon Cho, Joo-Hong Park, Sang-Uk Seo, Joo-Youn Cho, Wan-Uk Kim, Donghyun Kim

Faculty, Staff and Student Publications

OBJECTIVES: To investigate whether and how inflammatory disease in the intestine influences the development of arthritis, considering that organ-to-organ communication is associated with many physiological and pathological events.

METHODS: First, mice were given drinking water containing dextran sodium sulfate (DSS) and then subjected to inflammatory arthritis. We compared the phenotypic symptoms between the cohoused and separately-housed mice. Next, donor mice were divided into DSS-treated and untreated groups and then cohoused with recipient mice. Arthritis was then induced in the recipients. The fecal microbiome was analyzed by 16S rRNA amplicon sequencing. We obtained type strains of the candidate bacteria and generated …


Chromosomal Microarray Analysis Supplements Exome Sequencing To Diagnose Children With Suspected Inborn Errors Of Immunity, Breanna J Beers, Morgan N Similuk, Rajarshi Ghosh, Bryce A Seifert, Leila Jamal, Michael Kamen, Michael R Setzer, Colleen Jodarski, Rylee Duncan, Devin Hunt, Madison Mixer, Wenjia Cao, Weimin Bi, Daniel Veltri, Eric Karlins, Lingwen Zhang, Zhiwen Li, Andrew J Oler, Kathleen Jevtich, Yunting Yu, Haley Hullfish, Bibiana Bielekova, Pamela Frischmeyer-Guerrerio, An Dang Do, Laryssa A Huryn, Kenneth N Olivier, Helen C Su, Jonathan J Lyons, Christa S Zerbe, V Koneti Rao, Michael D Keller, Alexandra F Freeman, Steven M Holland, Luis M Franco, Magdalena A Walkiewicz, Jia Yan Jan 2023

Chromosomal Microarray Analysis Supplements Exome Sequencing To Diagnose Children With Suspected Inborn Errors Of Immunity, Breanna J Beers, Morgan N Similuk, Rajarshi Ghosh, Bryce A Seifert, Leila Jamal, Michael Kamen, Michael R Setzer, Colleen Jodarski, Rylee Duncan, Devin Hunt, Madison Mixer, Wenjia Cao, Weimin Bi, Daniel Veltri, Eric Karlins, Lingwen Zhang, Zhiwen Li, Andrew J Oler, Kathleen Jevtich, Yunting Yu, Haley Hullfish, Bibiana Bielekova, Pamela Frischmeyer-Guerrerio, An Dang Do, Laryssa A Huryn, Kenneth N Olivier, Helen C Su, Jonathan J Lyons, Christa S Zerbe, V Koneti Rao, Michael D Keller, Alexandra F Freeman, Steven M Holland, Luis M Franco, Magdalena A Walkiewicz, Jia Yan

Faculty, Staff and Students Publications

PURPOSE: Though copy number variants (CNVs) have been suggested to play a significant role in inborn errors of immunity (IEI), the precise nature of this role remains largely unexplored. We sought to determine the diagnostic contribution of CNVs using genome-wide chromosomal microarray analysis (CMA) in children with IEI.

METHODS: We performed exome sequencing (ES) and CMA for 332 unrelated pediatric probands referred for evaluation of IEI. The analysis included primary, secondary, and incidental findings.

RESULTS: Of the 332 probands, 134 (40.4%) received molecular diagnoses. Of these, 116/134 (86.6%) were diagnosed by ES alone. An additional 15/134 (11.2%) were diagnosed by …


Ems Administration Of Systemic Corticosteroids To Pediatric Asthma Patients: An Analysis By Severity And Transport Interval, Lauren Riney, Sam Palmer, Erik Finlay, Andrew Bertrand, Shannon Burcham, Phyllis Hendry, Manish Shah, Kathryn Kothari, David Ashby, Daniel Ostermayer, Olga Semenova, Benjamin N Abo, Benjamin Abes, Nichole Shimko, Emily Myers, Marshall Frank, Tim Turner, Mac Kemp, Kim Landry, Greg Roland, Jennifer Fishe Jan 2023

Ems Administration Of Systemic Corticosteroids To Pediatric Asthma Patients: An Analysis By Severity And Transport Interval, Lauren Riney, Sam Palmer, Erik Finlay, Andrew Bertrand, Shannon Burcham, Phyllis Hendry, Manish Shah, Kathryn Kothari, David Ashby, Daniel Ostermayer, Olga Semenova, Benjamin N Abo, Benjamin Abes, Nichole Shimko, Emily Myers, Marshall Frank, Tim Turner, Mac Kemp, Kim Landry, Greg Roland, Jennifer Fishe

Faculty, Staff and Students Publications

INTRODUCTION: Pediatric asthma exacerbations are a common cause of emergency medical services (EMS) encounters. Bronchodilators and systemic corticosteroids are mainstays of asthma exacerbation therapy, yet data on the efficacy of EMS administration of systemic corticosteroids are mixed. This study's objective was to assess the association between EMS administration of systemic corticosteroids to pediatric asthma patients on hospital admission rates based on asthma exacerbation severity and EMS transport intervals.

METHODS: This is a sub-analysis of the Early Administration of Steroids in the Ambulance Setting: An Observational Design Trial (EASI AS ODT). EASI AS ODT is a non-randomized, stepped wedge, observational study …


Case Report: Artemis Deficiency And 3m Syndrome-Coexistence Of Two Distinct Genetic Disorders, Ayca Ceylan, Ilyas Emre Tekdemir, Nadir Kocak, Ivan Kingyue Chinn, Jordan Scott Orange, Hasibe Artac Jan 2023

Case Report: Artemis Deficiency And 3m Syndrome-Coexistence Of Two Distinct Genetic Disorders, Ayca Ceylan, Ilyas Emre Tekdemir, Nadir Kocak, Ivan Kingyue Chinn, Jordan Scott Orange, Hasibe Artac

Faculty, Staff and Students Publications

The presence of two different genetic conditions in the same individual is possible, especially in populations with consanguinity. In this case report, we present the coexistence of Artemis deficiency (OMIM 602450) and Three M (3M) syndrome (OMIM 273750). A 10-months-old male patient with neuromotor developmental delay was evaluated for immunodeficiency due to recurrent respiratory infections diarrhea and oral moniliasis from the age of 1.5 months. He had facial dysmorphism with rotated ears, flat nose and hypertelorism. Neurological examination revealed generalized hypotonia and mental motor delay. Immunological screening of the patient demonstrated mild lymphopenia, hypogammaglobulinemia, reduced number of CD3


Combined Immunodeficiency Caused By Pathogenic Variants In The Zap70 C-Terminal Sh2 Domain, Cédric Mongellaz, Rita Vicente, Lenora M Noroski, Nelly Noraz, Valérie Courgnaud, Javier Chinen, Emilia Faria, Valérie S Zimmermann, Naomi Taylor Jan 2023

Combined Immunodeficiency Caused By Pathogenic Variants In The Zap70 C-Terminal Sh2 Domain, Cédric Mongellaz, Rita Vicente, Lenora M Noroski, Nelly Noraz, Valérie Courgnaud, Javier Chinen, Emilia Faria, Valérie S Zimmermann, Naomi Taylor

Faculty, Staff and Students Publications

INTRODUCTION: ZAP-70, a protein tyrosine kinase recruited to the T cell receptor (TCR), initiates a TCR signaling cascade upon antigen stimulation. Mutations in the ZAP70 gene cause a combined immunodeficiency characterized by low or absent CD8+ T cells and nonfunctional CD4+ T cells. Most deleterious missense ZAP70 mutations in patients are located in the kinase domain but the impact of mutations in the SH2 domains, regulating ZAP-70 recruitment to the TCR, are not well understood.

METHODS:Genetic analyses were performed on four patients with CD8 lymphopenia and a high resolution melting screening for ZAP70 mutations was developed. The impact of SH2 …


Covid-19 And Pregnancy: Clinical Outcomes; Mechanisms, And Vaccine Efficacy, Deepak Kumar, Sonam Verma, Indira U Mysorekar Jan 2023

Covid-19 And Pregnancy: Clinical Outcomes; Mechanisms, And Vaccine Efficacy, Deepak Kumar, Sonam Verma, Indira U Mysorekar

Faculty, Staff and Students Publications

As the COVID-19 pandemic continues into its third year, emerging data indicates increased risks associated with SARS-CoV-2 infection during pregnancy, including pre-eclampsia, intrauterine growth restriction, preterm birth, stillbirth, and risk of developmental defects in neonates. Here, we review clinical reports to date that address different COVID-19 pregnancy complications. We also document placental pathologies induced by SARS-CoV-2 infection, entry mechanisms in placental cells, and immune responses at the maternal-fetal interface. Since new variants of SARS-CoV-2 are emerging with characteristics of higher transmissibility and more effective immune escape strategies, we also briefly highlight the genomic and proteomic features of SARS-CoV-2 investigated to …


Editorial: Hemostasis In Ecmo And Vad, Volume Ii, Jun Teruya, Jean M Connors, Barbara Zieger Jan 2023

Editorial: Hemostasis In Ecmo And Vad, Volume Ii, Jun Teruya, Jean M Connors, Barbara Zieger

Faculty, Staff and Students Publications

No abstract provided.


From Concept To Delivery: A Yeast-Expressed Recombinant Protein-Based Covid-19 Vaccine Technology Suitable For Global Access, Peter J Hotez, Rakesh Adhikari, Wen-Hsiang Chen, Yi-Lin Chen, Portia Gillespie, Nelufa Y Islam, Brian Keegan, Rakhi Tyagi Kundu, Jungsoon Lee, Zhuyun Liu, Jason T Kimata, Numan Oezguen, Jeroen Pollet, Cristina Poveda, Kay Razavi, Shannon E Ronca, Ulrich Strych, Syamala R Thimmiraju, Leroy Versteeg, Maria Jose Villar-Mondragon, Junfei Wei, Bin Zhan, Maria Elena Bottazzi Jan 2023

From Concept To Delivery: A Yeast-Expressed Recombinant Protein-Based Covid-19 Vaccine Technology Suitable For Global Access, Peter J Hotez, Rakesh Adhikari, Wen-Hsiang Chen, Yi-Lin Chen, Portia Gillespie, Nelufa Y Islam, Brian Keegan, Rakhi Tyagi Kundu, Jungsoon Lee, Zhuyun Liu, Jason T Kimata, Numan Oezguen, Jeroen Pollet, Cristina Poveda, Kay Razavi, Shannon E Ronca, Ulrich Strych, Syamala R Thimmiraju, Leroy Versteeg, Maria Jose Villar-Mondragon, Junfei Wei, Bin Zhan, Maria Elena Bottazzi

Faculty, Staff and Students Publications

Introduction: The development of a yeast-expressed recombinant protein-based vaccine technology co-developed with LMIC vaccine producers and suitable as a COVID-19 vaccine for global access is described. The proof-of-concept for developing a SARS-CoV-2 spike protein receptor-binding domain (RBD) antigen as a yeast-derived recombinant protein vaccine technology is described.

Areas covered: Genetic Engineering: The strategy is presented for the design and genetic modification used during cloning and expression in the yeast system. Process and Assay Development: A summary is presented of how a scalable, reproducible, and robust production process for the recombinant protein COVID-19 vaccine antigen was developed. Formulation and Pre-clinical Strategy: …


Myeloid-Associated Differentiation Marker Is Associated With Type 2 Asthma And Is Upregulated By Human Rhinovirus Infection, Sasipa Tanyaratsrisakul, Alane Blythe C Dy, Francesca Polverino, Mari Numata, Julie G Ledford Jan 2023

Myeloid-Associated Differentiation Marker Is Associated With Type 2 Asthma And Is Upregulated By Human Rhinovirus Infection, Sasipa Tanyaratsrisakul, Alane Blythe C Dy, Francesca Polverino, Mari Numata, Julie G Ledford

Faculty, Staff and Students Publications

BACKGROUND: Human rhinoviruses are known to predispose infants to asthma development during childhood and are often associated with exacerbations in asthma patients. MYADM epithelial expression has been shown to associate with asthma severity. The goal of this study was to determine if MYADM expression patterns were altered in asthma and/or rhinovirus infection and if increased MYADM expression is associated with increased asthma-associated factors.

METHODS: Utilizing H1HeLa cells and differentiated primary human airway epithelial cells (AECs), we measured the expression of MYADM and inflammatory genes by qRT-PCR in the presence or absence of RV-1B infection or poly I:C treatment and with …


Alveolar Macrophages In Lung Cancer: Opportunities Challenges, Cheng-Yen Chang, Dominique Armstrong, David B Corry, Farrah Kheradmand Jan 2023

Alveolar Macrophages In Lung Cancer: Opportunities Challenges, Cheng-Yen Chang, Dominique Armstrong, David B Corry, Farrah Kheradmand

Faculty, Staff and Students Publications

Alveolar macrophages (AMs) are critical components of the innate defense mechanism in the lung. Nestled tightly within the alveoli, AMs, derived from the yolk-sac or bone marrow, can phagocytose foreign particles, defend the host against pathogens, recycle surfactant, and promptly respond to inhaled noxious stimuli. The behavior of AMs is tightly dependent on the environmental cues whereby infection, chronic inflammation, and associated metabolic changes can repolarize their effector functions in the lungs. Several factors within the tumor microenvironment can re-educate AMs, resulting in tumor growth, and reducing immune checkpoint inhibitors (ICIs) efficacy in patients treated for non-small cell lung cancer …


Effects Of Aging On Urinary Tract Epithelial Homeostasis And Immunity, Marianne M Ligon, Chetanchandra S Joshi, Bisiayo E Fashemi, Arnold M Salazar, Indira U Mysorekar Jan 2023

Effects Of Aging On Urinary Tract Epithelial Homeostasis And Immunity, Marianne M Ligon, Chetanchandra S Joshi, Bisiayo E Fashemi, Arnold M Salazar, Indira U Mysorekar

Faculty, Staff and Students Publications

A global increase in older individuals creates an increasing demand to understand numerous healthcare challenges related to aging. This population is subject to changes in tissue physiology and the immune response network. Older individuals are particularly susceptible to infectious diseases, with one of the most common being urinary tract infections (UTIs). Postmenopausal and older women have the highest risk of recurrent UTIs (rUTIs); however, why rUTIs become more frequent after menopause and during old age is incompletely understood. This increased susceptibility and severity among older individuals may involve functional changes to the immune system with age. Aging also has substantial …


Engaging Patients In Antimicrobial Stewardship: Co-Designed Educational Tool To Improve Periprocedural Care Through De-Implementation Of Guideline-Discordant Antimicrobial Use, Hawra Al Lawati, Marlena Shin, Rebecca Lamkin, Tyler Thompson, Isabella Epshtein, Hillary Mull, Dipandita Basnet Thapa, Dimitri Drekonja, Maria C Rodriguez-Barradas, Teena Huan Xu, Howard Gold, A Rani Elwy, Judy Strymish, Westyn Branch-Elliman Jan 2023

Engaging Patients In Antimicrobial Stewardship: Co-Designed Educational Tool To Improve Periprocedural Care Through De-Implementation Of Guideline-Discordant Antimicrobial Use, Hawra Al Lawati, Marlena Shin, Rebecca Lamkin, Tyler Thompson, Isabella Epshtein, Hillary Mull, Dipandita Basnet Thapa, Dimitri Drekonja, Maria C Rodriguez-Barradas, Teena Huan Xu, Howard Gold, A Rani Elwy, Judy Strymish, Westyn Branch-Elliman

Faculty, Staff and Students Publications

Effective de-implementation models often include replacement of an ineffective practice with an alternative. We co-developed patient education materials as a replacement strategy for inappropriate post-procedural antibiotics in cardiac device procedures. Lessons learned and developed materials may be used to promote infection prevention in other periprocedural settings.