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Neuroangiogenesis: A Vascular Basis For Alzheimer's Disease And Cognitive Decline During Aging, Charles T. Ambrose

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Angiogenesis directs development of the brain's microcirculation during antenatal and postnatal development, but its role later in life is less well recognized. I contend that during senescence a reduced cerebral capillary density accounts in part for the vascular cognitive impairment observed in many older persons and possibly for some forms of Alzheimer's disease. I propose that neuroangiogenesis is essential throughout adult life for maintaining the microcirculation of the cerebral cortex and elsewhere in the brain and that it commonly declines with old age. To support this hypothesis I have examined the neurological literature for relevant studies on cerebral capillary density …

Dynamics Of Envelope Evolution In Clade C Shiv-Infected Pig-Tailed Macaques During Disease Progression Analyzed By Ultra-Deep Pyrosequencing, For Yue Tso, Damien C. Tully, Sandra Gonzalez, Christopher Quince, On Ho, Patricia Polacino, Ruth M. Ruprecht, Shiu-Lok Hu, Charles Wood

Nebraska Center for Virology: Faculty Publications

Understanding the evolution of the human immunodeficiency virus type 1 (HIV-1) envelope during disease progression can provide tremendous insights for vaccine development, and simian-human immunodeficiency virus (SHIV) infection of nonhuman primate provides an ideal platform for such studies. A newly developed clade C SHIV, SHIV-1157ipd3N4, which was able to infect rhesus macaques, closely resembled primary HIV-1 in transmission and pathogenesis, was used to infect several pig-tailed macaques. One of the infected animals subsequently progressed to AIDS, whereas one remained a nonprogressor. The viral envelope evolution in the infected animals during disease progression was analyzed by a bioinformatics approach using ultra-deep …

Evaluation Of Age-Related Changes In Translocator Protein (Tspo) In Human Brain Using 11C-[R]-Pk11195 Pet, Ajay Kumar, Otto Muzik, Varun Shandal, Diane Chugani, Pulak Chakraborty, Harry T. Chugani

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

We studied the distribution and expression of translocator protein in the human brain using ¹¹C-[R]-PK-11195 positron emission tomography (PK11195 PET) and evaluated age-related changes.

Methods

A dynamic PK11195 PET scan was performed in 15 normal healthy adults (mean age: 29 ±8.5 years (range: 20 to 49); 7 males) and 10 children (mean age: 8.8 ±5.2 years (range: 1.2 to 17); 5 males), who were studied for potential neuroinflammation but showed no focally increased PK11195 binding. The PET images were evaluated by calculating standard uptake values and regional binding potential, based on a simplified reference region model, as …

Vitamin D Mitigates Age-Related Cognitive Decline Through The Modulation Of Pro-Inflammatory State And Decrease In Amyloid Burden, Teresita L. Briones, Hala Darwish

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Increasing evidence shows an association between the use of vitamin D and improvement in age-related cognitive decline. In this study, we investigated the possible mechanisms involved in the neuroprotective effects of vitamin D on age-related brain changes and cognitive function.

Methods

Male F344 rats aged 20 months (old) and 6 months (young) were used and randomly assigned to either vitamin D supplementation or no supplementation (control). A total of n = 39 rats were used in the study. Rats were individually housed and the supplementation group received a subcutaneous injection of vitamin D (1, α25-dihydroxyvitamin D3) 42 I.U./Kg …

Augmented Annotation And Orthologue Analysis For Oryctolagus Cuniculus: Better Bunny, Douglas B. Craig, Sujatha Kannan, Alan A. Dombkowski

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

The rabbit is an important model organism used in a wide range of biomedical research. However, the rabbit genome is still sparsely annotated, thus prohibiting extensive functional analysis of gene sets derived from whole-genome experiments. We developed a web-based application that provides augmented annotation and orthologue analysis for rabbit genes. Importantly, the application allows comprehensive functional analysis through the use of orthologous relationships.

Results

Using data extracted from several public bioinformatics repositories we created Better Bunny, a database and query tool that extensively augments the available functional annotation for rabbit genes. Using the complete set of target genes …

Vip And Host Immunity, Xiaoyu Jiang

Wayne State University Dissertations

The purpose of the current dissertation was to examine how VIP regulates host immunity and corneal healing, specifically, its control of growth factors and TLR expression in the P. aeruginosa infected cornea. Firstly, VIP treatment increased growth factor expression (EGF, GHF, FGF and VEGF) in infected cornea. Notably, treatment with a mixture of EGF, FGF and HGF prevented corneal perforation, reduced pro-inflammatory cytokines and bacterial plate count, while increasing anti-inflammatory cytokines and antimicrobials such as murine beta-defensin2 and 3.

We also investigated the expression of TLR-signaling pathways in P. aeruginosa infected corneas with or without VIP treatment. PCR array and …

Endoplasmic Reticulum Calcium-Independent Phospholipase A2 Gamma (Er-Ipla2Γ): Role In Oxidative Stress-Induced Lipid Peroxidation, Ca2+ Release, Phospholipid Homeostasis And Cell Death In The Kidney, Andre Chioke Eaddy

MUSC Theses and Dissertations

Acute kidney injury and chronic kidney disease are becoming more prevalent and have high morbidity and mortality, and despite several therapies targeted towards treating or preventing kidney injury, outcomes have been unchanged for many years. Calcium­independent phospholipase A2y (iPLA2γ) is one of seven Ca2+-independent PLA2 enzymes and represents a potential therapeutic target in kidney disease because of its unique subcellular localization and its potential as the putative membrane remodeling/repair enzyme. Studies in our laboratory suggest iPLA2γ is cytoprotective during oxidant injury by preventing and/or repairing oxidant-induced lipid peroxidation and pointed to ER-iPLA2γ as the major component of membrane repair and …

Premalignant Oral Lesion Immunobiology: Immune Modulation And Vaccination, Anna-Maria Alicia De Costa

MUSC Theses and Dissertations

While studies have indicated that squamous cell carcinoma of the head and neck (HNSCC) is associated with immune suppression, these studies did not analyze the immune response at the dysplastic stage. This study utilized a mouse model of 4-nitroquinoline 1-oxide (4NQO)-induced oral carcinogenesis to examine the alterations in immune phenotype at the premalignant and malignant stages of HNSCC. Cervical lymph nodes of HNSCC-bearing mice were found to contain a greater number of cells, including a greater number of conventional (Tconv) and regulatory (Treg) T cells, compared to lymph nodes of control and premalignant lesion-bearing mice. Premalignant lesion-bearing mouse lymph nodes …

The Florida Melanoma Trial I: A Prospective Multicenter Phase I/Ii Trial Of Postoperative Hypofractionated Adjuvant Radiotherapy With Concurrent Interferon-Alfa-2b In The Treatment Of Advanced Stage Iii Melanoma With Long-Term Toxicity Follow-Up, Steven E. Finkelstein, Andy Trotti, Nikhil Rao, Douglas Reintgen, Wayne Cruse, Lynn Feun, Vernon Sondak, Daohai Yu, Weiwei Zhu, Clement Gwede, Ronald Deconti

Surgery Faculty Publications

Radiotherapy (RT) and interferon-alfa-2b (IFN α-2b) have individually been used for adjuvant therapy stage III melanoma with high-risk pathologic features. We hypothesized that concurrent adjuvant RT and IFN α-2b may decrease the risk of regional recurrence following surgery with acceptable toxicity. A prospective multicenter phase I/II study was conducted to evaluate hypofractionated RT with concurrent IFN. Induction IFN α-2b, 20 MU/m2/d, was administered IV ×5 consecutive days every week for 4 weeks. Next, RT 30 Gy in 5 fractions was given with concurrent IFN α-2b, 10 MU/m2 SQ 3 times per week on days alternating with …

Humor-Related Social Exchanges And Mental Health In Assisted Living Residents, Ann Elizabeth Mcqueen

Dissertations and Theses

Social contact is known to be vital for older adults' mental and physical health, but few studies of social interactions have taken place in long-term care settings. The current study investigated whether the psychological well-being of assisted living residents was influenced by factors associated with residents' social interactions involving humor. Specific aims of the present study were to develop and test a measure related to humor-related social exchanges, to examine how humor-related social exchanges affect residents' mental health, and to explore whether humor-related social exchanges mediated the effects of resident and facility characteristics on indices of mental health. One hundred …

Role Of The Immune System And Bioactive Lipids In Trafficking Bone Marrow-Derived Stem Cells In Patients With Ischemic Heart Disease, Ahmed Abdel-Latif

Theses and Dissertations--Microbiology, Immunology, and Molecular Genetics

Acute myocardial infarction (AMI) triggers the mobilization of stem/progenitor cells from bone marrow (BMSPCs) into peripheral blood (PB). The underlying mechanisms orchestrating this mobilization and subsequent homing of BMSPCs to the myocardium are poorly understood. While the role of traditional chemokines in the mobilization and homing of hematopoietic stem cell (HSCs) to BM niches is undisputed, their role in directing BMSPCs to the highly proteolytic environment of the ischemic myocardium is debatable and other redundant mechanism may exist. Based on our observation that bioactive lipids, such as sphingosine-1 phosphate (S1P) and ceramide-1 phosphate (C1P), play an important role in regulating …

Does The Afferent Tubular Segment In An Orthotopic Bladder Substitution Compromise Ureteric Antireflux Properties? An Experimental Study In Dogs, Hassan Abol- Enein, Nuzhat Faruqui, Nashwa Barakat, Ahmed A. Shokeir

Section of Urology

Objective: To study the effects of a short ureter on renal function and histology in an orthotopic bladder substitution model using a long afferent limb, in a canine model.
Materials and methods: The study included nine adult mongrel dogs. A 40-cm segment of ileum was isolated, the distal half detubularized, configured into a U-shape and sutured to form a flat plate; this was then used to augment the bladder. The proximal half of the isolated ileum remained in continuity with the enterocystoplasty to form an isoperistaltic ileal ‘chimney’. The left ureter was divided at its lumbar part and …

Attenuation Of Corneal Myofibroblast Development Through Nanoparticle-Mediated Soluble Transforming Growth Factor-Β Type Ii Receptor (Stgfβrii) Gene Transfer, Ajay Sharma, Jason T. Rodier, Ashish Tandon, Alexander M. Klibanov, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

Purpose: To explore (i) the potential of polyethylenimine (PEI)-DNA nanoparticles as a vector for delivering genes into human corneal fibroblasts, and (ii) whether the nanoparticle-mediated soluble extracellular domain of the transforming growth factor–β type II receptor (sTGFβRII) gene therapy could be used to reduce myofibroblasts and fibrosis in the cornea using an in vitro model.

Methods: PEI-DNA nanoparticles were prepared at a nitrogen-to-phosphate ratio of 30 by mixing linear PEI and a plasmid encoding sTGFβRII conjugated to the fragment crystallizable (Fc) portion of human immunoglobulin. The PEI-DNA polyplex formation was confirmed through gel retardation assay. Human corneal fibroblasts (HCFs) were …

Biochemical Links Between Hormonal Mediators Of Psychological Stress And The Expression Of Muc1 In Prostate Cancer Cells, Kristina Andrijauskaite

MUSC Theses and Dissertations

A growing body of scientific evidence has demonstrated that chronic psychological stress can not only increase the growth and metastasis of tumors through a number of mechanisms, such as by an increase of VEGF and Bcl-2, but also can decrease the survival of cancer patients. However, no studies have reported the effect of psychological stress with respect to the tumor marker MUC1. Therefore, building upon previous research, the purpose of the present study was to investigate the effect of the stress hormones cortisol and norepinephrine on the tumor marker MUC1, which is highly associated with tumor cell metastasis and is …

Brain-Computer Interfaces In Medicine, Jerry J. Shih, Dean J. Krusienski, Johnathan R. Wolpaw

Electrical & Computer Engineering Faculty Publications

Brain-computer interfaces (BCIs) acquire brain signals, analyze them, and translate them into commands that are relayed to output devices that carry out desired actions. BCIs do not use normal neuromuscular output pathways. The main goal of BCI is to replace or restore useful function to people disabled by neuromuscular disorders such as amyotrophic lateral sclerosis, cerebral palsy, stroke, or spinal cord injury. From initial demonstrations of electroenceph-alography-based spelling and single-neuron-based device control, researchers have gone on to use electroenceph-alographic, intracortical, electrocorticographic, and other brain signals for increasingly complex control of cursors, robotic arms, prostheses, wheelchairs, and other devices. Brain-computer interfaces …

Factors Associated With Myopia In School Children In China: The Beijing Childhood Eye Study, Qi Sheng You, Li Juan Wu, Jia Li Duan, Yan Xia Luo, Li Juan Liu, Xia Li, Qi Gao, Wei Wang, Liang Xu, Jost Jonas, Xiu Hua Guo

Research outputs 2012

Purpose: To assess factors associated with myopia in school children in rural and urban parts of Greater Beijing. Methods: The Beijing Pedriatic Eye Study was a population-based cross-sectional study, in which one school of each level (primary, junior high, senior high) was randomly selected from nine randomly selected districts out of 18 districts of Greater Beijing. The children underwent non-cylcoplegic refractometry and their parents an interview. Results: Of 16,771 eligible students, 15,066 (89.8%) children (7,769 (51.6%) girls) participated, with 8,860 (58.8%) participants living in the rural region. Mean age was 13.263.4 years (range:7–18 years). In multivariate analysis, prevalence of myopia …

Ginger And Osteoarthritis, Tessa Therkleson

Research outputs 2012

Ginger has been used for 1000s of years as a food and medicine; it is likely one of the most ancient remedies valued by humans. Ancient Indian and Chinese cultures reportedly used ginger for a wide variety of conditions and modern day research has found it effective as an anti-emetic and anti-inflammatory agent, when taken internally. Random controlled trials using ginger extract have been found effective in relieving symptoms of osteoarthritis. Osteoarthritis is the primary cause of musculoskeletal pain and disability in Western cultures. Current management is primarily through the use of anti-inflammatory and analgesic medication, with cortisone injections and …

Promoting Mitochondrial Biogenesis With The Sirti Activator Srt1720 To Improve Mitochondrial And Renal Function After Acute Kidney Injury, Jason Allen Funk

MUSC Theses and Dissertations

Mitochondrial dysfunction is a primary pathological consequence of acute kidney injury (AKI). Induction of mitochondrial biogenesis via the nuclear coactivator of transcription PPARγ-coactivator-1α (PGC-1α), the master regulator of mitochondrial biogenesis, rescues mitochondrial function in renal cells after oxidant injury. The primary goal of this project was to evaluate the recovery of mitochondrial function after in vivo AKI, and to determine the influence of mitochondrial biogenesis during the repair process. Deacetylation of PGC-1α by the class III HDAC SIRT1 produces a more active form of the protein and stimulates mitochondrial biogenesis. The potent SIRT1 activator SRT1720 induced deacetylation of PGC-1α, increased …

Long Term Weight Variability In Adults Of Adventist Health Study 1 And 2, Namgyal Lhawang Kyulo

Loma Linda University Electronic Theses, Dissertations & Projects

Background: The effect of overweight and obesity on the risk of fatal disease tends to attenuate with age. One plausible explanation is that a proportion of elderly people in the ideal weight category (19 to 25 kg/m ) experienced disease-related weight loss - an effect that will attenuate health risk related to overweight and obesity. One potential approach to controlling for this bias would be to examine fluctuations in weight during the adult lifespan by considering multiple measures of weight or recall of body weight during adulthood. Some of these measures are available in the Adventist Health Study cohorts and …

Mir-128 Inhibits Tumor Growth And Angiogenesis By Targeting P70s6k1., Zhu-Mei Shi, Jing Wang, Zhiping Yan, Yong-Ping You, Chong-Yong Li, Xu Qian, Yu Yin, Peng Zhao, Ying-Ying Wang, Xie-Feng Wang, Ming-Na Li, Ling-Zhi Liu, Ning Liu, Bing-Hua Jiang

Kimmel Cancer Center Faculty Papers

MicroRNAs are a class of small noncoding RNAs that function as critical gene regulators through targeting mRNAs for translational repression or degradation. In this study, we showed that miR-128 expression levels were decreased in glioma, and identified p70S6K1 as a novel direct target of miR-128. Overexpression of miR-128 suppressed p70S6K1 and its downstream signaling molecules such as HIF-1 and VEGF expression, and attenuated cell proliferation, tumor growth and angiogenesis. Forced expression of p70S6K1 can partly rescue the inhibitory effect of miR-128 in the cells. Taken together, these findings will shed light to the role and mechanism of miR-128 in regulating …

Early Versus Delayed Decompression For Traumatic Cervical Spinal Cord Injury: Results Of The Surgical Timing In Acute Spinal Cord Injury Study (Stascis)., Michael G Fehlings, Alex R. Vaccaro, Jefferson R Wilson, Anoushka Singh, David W Cadotte, James Harrop, Bizhan Aarabi, Christopher Shaffrey, Marcel Dvorak, Charles Fisher, Paul Arnold, Eric M Massicotte, Stephen Lewis, Raja Rampersaud

Department of Orthopaedic Surgery Faculty Papers

BACKGROUND: There is convincing preclinical evidence that early decompression in the setting of spinal cord injury (SCI) improves neurologic outcomes. However, the effect of early surgical decompression in patients with acute SCI remains uncertain. Our objective was to evaluate the relative effectiveness of early (injury) versus late (≥ 24 hours after injury) decompressive surgery after traumatic cervical SCI.

METHODS: We performed a multicenter, international, prospective cohort study (Surgical Timing In Acute Spinal Cord Injury Study: STASCIS) in adults aged 16-80 with cervical SCI. Enrolment occurred between 2002 and 2009 at 6 North American centers. The primary outcome was ordinal change …

Microbubble Mediated Thrombus Dissolution With Diagnostic Ultrasound For The Treatment Of Chronic Venous Thrombi., Shelby Kutty, Juefei Wu, James M. Hammel, Feng Xie, Shunji Gao, Lucas K. Drvol, John Lof, Stanley J. Radio, Stacey L. Therrien, David A. Danford, Thomas R. Porter

Journal Articles: Pediatrics

BACKGROUND: Central venous catheter (CVC) thrombi result in significant morbidity in children, and currently available treatments are associated with significant risk. We sought to investigate the therapeutic efficacy of microbubble (MB) enhanced sonothrombolysis for aged CVC associated thrombi in vivo.

METHODS AND RESULTS: A model of chronic indwelling CVC in the low superior vena cava with thrombus in situ was established after feasibility and safety testing in 7 pigs; and subsequently applied for repeated, sonothrombolytic treatments in 9 pigs (total 24 treatments). Baseline intracardiac echocardiography (ICE, 10.5F, Siemens), fluoroscopy and saline flushing confirmed the absence of any pre-existing CVC thrombus. …

Cardioprotection Of Controlled And Cardiac-Specific Over-Expression Of A(2a)-Adenosine Receptor In The Pressure Overload., Eman A Hamad, Weizhong Zhu, Tung O Chan, Valerie Myers, Erhe Gao, Xue Li, Jin Zhang, Jianliang Song, Xue-Qian Zhang, Joseph Y Cheung, Walter Koch, Arthur M Feldman

Center for Translational Medicine Faculty Papers

Adenosine binds to three G protein-coupled receptors (R) located on the cardiomyocyte (A(1)-R, A(2A)-R and A(3)-R) and provides cardiac protection during both ischemic and load-induced stress. While the role of adenosine receptor-subtypes has been well defined in the setting of ischemia-reperfusion, far less is known regarding their roles in protecting the heart during other forms of cardiac stress. Because of its ability to increase cardiac contractility and heart rate, we hypothesized that enhanced signaling through A(2A)-R would protect the heart during the stress of transverse aortic constriction (TAC). Using a cardiac-specific and inducible promoter, we selectively over-expressed A(2A)-R in FVB …

Orphan Nuclear Receptor Nur77 Regulates Androgen Receptor Gene Expression In Mouse Ovary., Anyi Dai, Guijun Yan, Qinyuan He, Yue Jiang, Qun Zhang, Ting Fang, Lijun Ding, Jianxin Sun, Haixiang Sun, Yali Hu

Center for Translational Medicine Faculty Papers

The androgen receptor (AR) is a nuclear receptor that is expressed in growing follicles and involved in folliculogenesis and follicle growth. The orphan nuclear receptor, Nur77, also has an important role in steroid signaling and follicle maturation. We hypothesized that AR levels and androgen signaling through AR are regulated by Nur77 in the ovary. In the ovaries of Nur77 knockout mice (n = 5), real-time PCR results showed that the mRNA levels of AR and an androgen signaling target gene, Kitl, were decreased by 35% and 24%, respectively, relative to wild-type mice (n = 5), which suggested transcriptional regulation of …

Microrna-145 Protects Cardiomyocytes Against Hydrogen Peroxide (H₂O₂)-Induced Apoptosis Through Targeting The Mitochondria Apoptotic Pathway., Ruotian Li, Guijun Yan, Qiaoling Li, Haixiang Sun, Yali Hu, Jianxin Sun, Biao Xu

Center for Translational Medicine Faculty Papers

MicroRNAs, a class of small and non-encoding RNAs that transcriptionally or post-transcriptionally modulate the expression of their target genes, has been implicated as critical regulatory molecules in many cardiovascular diseases, including ischemia/reperfusion induced cardiac injury. Here, we report microRNA-145, a tumor suppressor miRNA, can protect cardiomyocytes from hydrogen peroxide H₂O₂-induced apoptosis through targeting the mitochondrial pathway. Quantitative real-time PCR (qPCR) demonstrated that the expression of miR-145 in either ischemia/reperfused mice myocardial tissues or H₂O₂-treated neonatal rat ventricle myocytes (NRVMs) was markedly down-regulated. Over-expression of miR-145 significantly inhibited the H₂O₂-induced cellular apoptosis, ROS production, mitochondrial structure disruption as well as the …

Is Aspirin Effective In Helping To Prevent Breast Cancer In Women Ages 45 Years And Older?, Kristen M. Quartuccio

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this selective EBM review is to determine whether or not aspirin is effective in helping to prevent breast cancer in women ages 45 years and older.

STUDY DESIGN: Review of three English language primary studies published in 2005, 2007, and 2008

DATA SOURCES: Two randomized, double blind, placebo controlled clinical trials and one prospective, population based cohort study comparing aspirin to placebo were found using PubMed and Cochrane databases.

OUTCOMES MEASURED: Breast cancer development was measured in several ways. Tumor characteristics were measured at diagnosis, including size, metastasis to lymph nodes, histology of the mass, histology …

Identifying Sm22 As A Key Player In Arterial Diseases, Jianbin Shen

Wayne State University Dissertations

Background : Expression of vascular smooth muscle cell (VSMC) cytoskeleton markers including SM22 is down-regulated in arterial diseases including atherosclerosis where inflammation and osteochondrogenesis are present. However, the role of this downregulation in arterial pathogenesis is unknown. Hypothesis : Downregulation of SM22 may actively contribute to arterial pathogenesis. Methods : Five Sm22 knockout (Sm22^-/-) mice and their wild type littermates were subjected to carotid artery denudation, an artery injury model. Analyses were conducted on carotid arteries 2 weeks after injury. Primary VSMCs were isolated from mouse aortas and investigated individually at passage 2 to 4. Sm22 knockdown was …

Role Of Thromboxane Receptor-Alpha In Prostate Cancer Progression, Prasanna Ekambaram

Wayne State University Dissertations

Thromboxane A2 (TXA2) is a major arachidonic acid metabolite that signals through TXA2 receptors (TP) to induce platelet aggregation and smooth muscle contraction. TXA2 receptors are expressed as two different isoforms in humans, namely TP-alpha (TPα) and TP-beta (TPβ), which have common and distinct signaling pathways. Of the two TP receptor isoforms, studies have shown that TPα impacts tumor growth and progression of lung cancer. Previously our studies demonstrated that activation of Thromboxane receptor by TXA2 agonists could regulate prostate cancer (PCa) cell motility and cytoskeletal reorganization through activation of Rho-A. The primary objective of this study is to investigate …

A Role For Reactive Oxygen Species In Photodynamic Therapy, Michael Price

Wayne State University Dissertations

Photodynamic therapy (PDT) is based on the ability of certain photosensitizing agents to selectively localize in neoplastic cells and their vasculature. Subsequent irradiation at a wavelength corresponding to a photosensitizer absorbance band excites the photosensitizer molecules, leading to energy transfer reactions and fluorescence. It was initially concluded that the phototoxic effect occurred when energy from the excited state of the photosensitizer was transferred to dissolved oxygen to form singlet oxygen. This product has a very brief half-life and will cause cellular damage only in the immediate vicinity of its formation. But an excited-state photosensitizer can also interact with oxygen to …

Substance P And The Host Immune Response, Megan Elizabeth Foldenauer

Wayne State University Dissertations

This body of work examined the mechanism by which SP regulates host immunity, specifically, its control of growth factors and TLR expression in the P. aeruginosa-infected cornea. The role of mTOR and VIP in corneal infection and inflammation also was tested.

SP has a dual role in bacterial infection, unexpectedly upregulating growth factor production. This was accompanied by macrophage-specific upregulation of pro-inflammatory cytokines, downregulation of anti-inflammatory cytokines, and upregulation of anti-apoptotic genes, as well as a decrease in arginase-producing macrophages (M2 cells), important in stromal healing in these mice. All of these lead to worsened disease, despite the stimulatory effects …