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A Retrospective Study On The Effect Of Immunotherapy Treatment On Nasal Polyposis., Johanna Haejean Yun

College of Arts & Sciences Senior Honors Theses

Inside the paranasal sinuses, multiple saclike masses protrude from the lining, blocking one’s sense of taste and smell, clogging one’s nose with nasal congestion, and causing a continuous runny nose with postnasal drip. This is a common case of nasal polyposis. Nasal polyposis affects up to four percent of the general population, making it one of the most common chronic diseases of the upper respiratory tract (Settipane 1996). Moreover, in cadaveric studies, the prevalence has been as high as 40% (Larson et al 1994). Nasal polyps commonly occur in adults over the age of 40, predominantly in males—with a 2:1 …

Regulation Of Macrophage Inflammatory Signaling Pathways By Amp-Activated Protein Kinase., Yanfang Zhu

Electronic Theses and Dissertations

AMP-activated protein kinase, AMPK, is a conserved serine/threonine kinase with a critical function in the regulation of metabolic pathways in eukaryotic cells. Recently, AMPK has been shown to play an additional role as a regulator of inflammatory activity in leukocytes. Treatment of macrophages with chemical AMPK activators, or forced expression of a constitutively active form of AMPK, results in polarization to an antiinflammatory phenotype. Additionally, we reported previously that stimulation of macrophages with antiinflammatory cytokines such as IL-10, IL-4 and TGF-ß results in rapid activation of AMPK, suggesting that AMPK contributes to the suppressive function of these cytokines. In the …

Interleukin-6 And Soluble Interleukin-6 Receptor Levels In Posttraumatic Stress Disorder : Associations With Lifetime Diagnostic Status And Psychological Context., Tamara L. Newton, Rafael Fernandez-Botran, James J. Miller, Vicki Ellison Burns

Faculty Scholarship

This study correlated lifetime PTSD diagnostic status with interleukin-6 (IL-6) and soluble IL-6 receptor (sIL-6R) levels, and tested whether these correlations are sensitive to psychological context. Midlife women attended two research visits where blood was drawn (beginning of visits) and saliva and oral mucosal transudate were collected (beginning and end of visits) to measure IL-6 and sIL-6R. Women were classified as PTSD−/− (past and current symptoms below subsyndromal levels), PTSD+/− (past symptoms at or above subsyndromal levels), or PTSD +/+ (past and current symptoms at or above subsyndromal levels). PTSD+/+ women, compared to the other women, showed more negative emotion …

The Effect Of Mutations In Prmt5 On Its Ability To Oligomerize, Rachel Scarl

Senior Honors Projects

Atherosclerosis is a cardiovascular disease caused by a chronic inflammatory response in the cells lining blood vessels, vascular endothelial cells. In these cells, a network of interacting proteins regulates inflammation. One of these proteins, PRMT5, regulates the inflammatory response by methylating other proteins involved in inflammation. For PRMT5 to carry out its function, it must first oligomerize with itself and various other proteins. In this study, I determined whether mutations to specific PRMT5 methylation sites affect its ability to oligomerize. By expressing PRMT5 in HEK293 cells and studying the effects of adding a chemical cross-linking agent, DMS, I was able …

Influence Of Dietary Modification And/Or Exercise On Markers Of Inflammation In Male Rats, Trint Arlon Gunnels

Electronic Theses and Dissertations

The goal of the investigation was to examine the influence of a dietary intervention, with/without exercise, on markers of inflammation in plasma. Male Long-Evans rats (n = 28, aged 3-4 weeks) were assigned to either a “Daniel Fast” or “Western Diet” with/without exercise training for 13 weeks. Regular exercise training was performed three days a week. Following the 13-week intervention, the animals were sacrificed, followed by blood collection. Cytokines were measured via a magnetic bead panel assay. No statistical significance was found between groups (p > 0.05); however, a pattern was noted for both IL-1β and IL-10. Body weight gain was …

Increased Circulatory Lipopolysaccharide From A High Fat Diet Aggravates Inflammation And Exacerbates Renal Failure, Samuel Righi

Theses and Dissertations

Kidney failure is frequently associated with the risk factors linked to metabolic syndrome. Lipopolysaccharide (LPS) is a potent inflammatory molecule, which has increased absorption from the gut into blood circulation following a high fat and high-energy diet. We hypothesized that LPS from a high fat diet can amplify inflammation, thereby exacerbating chronic kidney disease and associated disorders. We have found that adding a high fat diet to renal insufficient mice significantly progressed their kidney disease as well as associated disorders, compared to both a high fat diet and renal insufficiency alone. Additionally, we were able to demonstrate in vitro that …

Benefits Of Exercise Intervention In Reducing Neuropathic Pain, John L. Dobson, James L. Mcmillan, Li Li

Department of Health Sciences and Kinesiology Faculty Publications

Peripheral neuropathy is a widespread and potentially incapacitating pathological condition that encompasses more than 100 different forms and manifestations of nerve damage. The diverse pathogenesis of peripheral neuropathy affects autonomic, motor and/or sensory neurons, and the symptoms that typify the condition are abnormal cutaneous sensation, muscle dysfunction and, most notably, chronic pain. Chronic neuropathic pain is difficult to treat and is often characterized by either exaggerated responses to painful stimuli (hyperalgesia) or pain resulting from stimuli that would not normally provoke pain (allodynia). The objective of this review is to provide an overview of some pathways associated with the development …

Dietary Antiaging Phytochemicals And Mechanisms Associated With Prolonged Survival, Hongwei Si, Dongmin Liu

Human Sciences Faculty Research

Aging is well-known an inevitable process that is influenced by genetic, lifestyle and environmental factors. However, the exact mechanisms underlying the aging process are not well understood. Increasing evidence shows that aging is highly associated with chronic increase in reactive oxygen species (ROS), accumulation of a low-grade proinflammatory phenotype and reduction in age-related autophagy, suggesting that these factors may play important roles in promoting aging. Indeed, reduction of ROS and low-grade inflammation and promotion of autophagy by calorie restriction or other dietary manipulation can extend lifespan in a wide spectrum of model organisms. Interestingly, recent studies show that some food-derived …

Therapeutic Implications Of Estrogen For Cerebral Vasospasm And Delayed Cerebral Ischemia Induced By Aneurysmal Subarachnoid Hemorrhage., Dale Ding, Robert M Starke, Aaron S Dumont, Gary K Owens, David M Hasan, Nohra Chalouhi, Md, Ricky Medel, Chih-Lung Lin

Department of Neurosurgery Faculty Papers

Cerebral vasospasm (CV) remains the leading cause of delayed morbidity and mortality following aneurysmal subarachnoid hemorrhage (SAH). However, increasing evidence supports etiologies of delayed cerebral ischemia (DCI) other than CV. Estrogen, specifically 17 β -estradiol (E2), has potential therapeutic implications for ameliorating the delayed neurological deterioration which follows aneurysmal SAH. We review the causes of CV and DCI and examine the evidence for E2-mediated vasodilation and neuroprotection. E2 potentiates vasodilation by activating endothelial nitric oxide synthase (eNOS), preventing increased inducible NOS (iNOS) activity caused by SAH, and decreasing endothelin-1 production. E2 provides neuroprotection by increasing thioredoxin expression, decreasing c-Jun N-terminal …

Voluntary Exercise Reduces Alzheimer’S-Like Pathology After Inflammation In Mice, Marielle K. Weintraub, Jordon D. White, Stephanie M. Turner, Samantha L. Hodges, Amanda Leigh Morin, Lindsey N. Sadler, Gary W. Boehm, Michael J. Chumley

International Journal of Exercise Science: Conference Proceedings

Current global statistics estimate that 44.4 million people are afflicted with dementia, and that 50%-75% of these patients suffer from Alzheimer’s disease (AD; Prince et al. 2013). AD, a progressive disorder categorized by neuronal and behavioral deterioration, is the 6^th leading cause of death in America (Alz facts and figure 2012). One hallmark pathology of AD is the presence of amyloid-beta (Aβ) in the brain, which can limit cell-to-cell communication, leading to cognitive deficits, and neuronal cell death. Although the exact origins of this disease still remain unknown, one possible catalyst of AD pathology is inflammation. Our lab has …

Immature Myeloid Cells Promote Tumor Formation Via Non-Suppressive Mechanism, Myrna Lillian Ortiz

USF Tampa Graduate Theses and Dissertations

ABSTRACT

Although there is ample evidence linking chronic inflammation with cancer, the cellular mechanisms involved in early events leading to tumor development remain unclear. Myeloid cells are an intricate part of inflammation. They consist of mature cells represented by macrophages, dendritic cells and granulocytes and a population of Immature Myeloid Cells (IMC), which in healthy individuals are cells in transition to mature cells. There is a substantial expansion of IMC in cancer and many other pathological conditions which is associated with pathologic activation of these cells. As a result, these cells acquire the ability to suppress immune responses and are …

T-Cell Mediated Mechanisms Of Autoimmunity, Anti-Tumor Immunity And Tumorigenesis, Jason Miska

Open Access Dissertations

The difficulty in identifying a tumor-specific antigen (TSA) in a majority of tumors poses a clinical problem in treating cancer with immunotherapy. To date, the majority of tumor antigens identified are not tumor-specific, but are rather largely “self” in nature, and the destruction of these tissues appear to be similar to autoimmune damage of normal tissues. Indeed, clinical studies of successful immune checkpoint therapies like such as anti-CTLA4 and anti-PD1/PD-L1 antibody treatment revealed a strong association of autoimmune side effects with therapeutic benefit. In these cases the anti-tumor effect seems to be mediated by, in part, an autoimmune response. The …

Blockade Of Mast Cell Activation Reduces Cutaneous Scar Formation, Lin Chen, Megan Schrementi, Matthew J. Ranzer, Traci A. Wilgus, Luisa A. Dipietro

Faculty Publications & Research

Damage to the skin initiates a cascade of well-orchestrated events that ultimately leads to repair of the wound. The inflammatory response is key to wound healing both through preventing infection and stimulating proliferation and remodeling of the skin. Mast cells within the tissue are one of the first immune cells to respond to trauma, and upon activation they release pro-inflammatory molecules to initiate recruitment of leukocytes and promote a vascular response in the tissue. Additionally, mast cells stimulate collagen synthesis by dermal fibroblasts, suggesting they may also influence scar formation. To examine the contribution of mast cells in tissue repair, …

An Intestinal Commensal Symbiosis Factor Controls Neuroinflammation Via Tlr2-Mediated Cd39 Signalling, Yan Wang, Kiel M. Telesford, Javier Ochoa-Repáraz, Sakhina Haque-Begum, Marc Christy, Eli J. Kasper, Li Wang, Yan Wu, Simon C. Robson, Dennis L. Kasper, Lloyd H. Kasper

Dartmouth Scholarship

The mammalian immune system constitutively senses vast quantities of commensal bacteria and their products through pattern recognition receptors, yet excessive immune reactivity is prevented under homeostasis. Intestinal microbiome can influence host susceptibility to extra-intestine autoimmune disorders. Here we report that polysaccharide A (PSA), a symbiosis factor for human intestinal commensal Bacteroides fragilis, protects against central nervous system demyelination and inflammation during experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis, through toll-like receptor 2 (TLR2). TLR2 mediates tissue-specific expansion of a critical regulatory CD39+ CD4 T cell subset by PSA. Ablation of CD39 signaling abrogates PSA control of EAE …

Depressive Symptoms And Inflammatory Indexes Are Modulated By Moderate Aerobic Exercise Training In Post-Menopausal Women, Ana M. Teixeira, Bahktyar Tartibian, Sodabeh Sharabiani

International Journal of Exercise Science: Conference Proceedings

Introduction: The aim of present study was to investigate the effects of moderate intensity exercise training on depressive and inflammatory markers in post-menopausal women.

Methods: Forty healthy postmenopausal women (55.1± 3.51 years) volunteered to participate in this study. The study design and its potential risks and benefits were fully explained before providing written informed consent, and approved by the human health committee of Urmia University, IRAN. At resting, the subjects were randomly assigned to one of the exercise (n=20) or control (n=20) groups. The exercise group performed aerobic exercise training (60%-70% MHR) 30-45 min/day, 3 times a week, for 12 …

Profile Of Cytokines And Soluble Tnf Receptors In Response To Moderate And Intense Exercises In Active And Remission Patients With Systemic Lupus Erythematosus, Luiz Augusto Perandini, Diego Sales-De-Oliveira, Suzana Beatriz Mello, Niels Olsen Camara, Fernanda Rodrigues Lima, Eduardo Borba, Eloisa Bonfá, Ana Lucia Sá-Pinto, Bruno Gualano

International Journal of Exercise Science: Conference Proceedings

Introduction: systemic lupus erythematosus (SLE) is a rheumatic autoimmune disease characterized by chronic inflammation that is associated with clinical symptoms and disease severity. Therefore, strategies to reduce inflammation, such as physical exercise, have a potential therapeutic role in SLE due to its anti-inflammatory effects. This study sought to compare cytokines and soluble TNF receptors response to: (1) moderate vs. intense aerobic exercise in active SLE (SLE_ACT) and remission SLE (SEL_REM) patients; (2) SLE_ACT vs. SLE_REM patients undergoing moderate and intense aerobic exercises; and (3) SLE patients vs. healthy controls (HC) undergoing moderate and intense …

Assessment Of Neutrophil Functional Activity Following Prolonged Endurance Exercise, Katsuhiko Suzuki, Kaoru Sugama, Kayo Yoshitani, Koso Shiraishi, Takashi Kometani, Shigeki Miura, Hiroshi Yoshioka, Yuichi Mori

International Journal of Exercise Science: Conference Proceedings

Introduction: Neutrophils not only play an important role in host defense by migrating to the site of infection and producing reactive oxygen species (RO S), but also mediate pathological process in inflammatory tissue damage. Therefore, it is import ant not only to assess but also modulate neutrophil activities for disease prevention. We hav e reported that exhaustive exercise causes neutrophil priming (Suzuki et al. J. Appl. Physiol. , 81, 1213-1222, 1996) which might be associated wi th muscle damage (Suzuki et al. J. Appl. Physiol. , 87, 1360-1367, 1999), but antioxidant capacity is also activated following exercise (Suzuki et al. …

Assessment Of Neutrophil Functional Activity Following Prolonged Endurance Exercise, Katsuhiko Suzuki, Kaoru Sugama, Kayo Yoshitani, Koso Shiraishi, Takashi Kometani, Shigeki Miura, Hiroshi Yoshioka, Yuichi Mori

International Journal of Exercise Science: Conference Proceedings

ntroduction: Neutrophils not only play an important role in host defense by migrating to the site of infection and producing reactive oxygen species (RO S), but also mediate pathological process in inflammatory tissue damage. Therefore, it is import ant not only to assess but also modulate neutrophil activities for disease prevention. We hav e reported that exhaustive exercise causes neutrophil priming (Suzuki et al. J. Appl. Physiol. , 81, 1213-1222, 1996) which might be associated wi th muscle damage (Suzuki et al. J. Appl. Physiol. , 87, 1360-1367, 1999), but antioxidant capacity is also activated following exercise (Suzuki et al. …

Regulation Of Immunological Pathways By Micrornas In Health And Disease, Barbara Wessner

International Journal of Exercise Science: Conference Proceedings

MicroRNAs (miRNAs) are small, non-coding, single stranded RNA molecules (19-24 nucleotides in length) that influence mRNA or protein levels by promoting either mRNA degradation or by preventing protein translation. In silico target prediction has revealed that they might regulate more than two thirds of human genes therefore playing an important role in physiological as well as pathophysiological processes (Ambros 2004; Lim, Lau et al. 2005). As such miRNAs have been identified as mediators of biological processes such as inflammation, angiogenesis, mitochondrial metabolism, cardiac and skeletal muscle contractile force generation and muscle hypertrophy and are suggested to play a significant role …

Gut Microflora And Health, Ryoichi Nagatomi Prof.

International Journal of Exercise Science: Conference Proceedings

Human gastrointestinal tract harbors a diverse population of microorganisms, the gut microbiata, the largest microbial community associated with human body, comprised of trillions of bacterial cells of over 1000 species. Although gut lumen is an extension of the external world for our organs and tissues, the interaction between human body and gut microbiata is highly mutual and reciprocal as if it is one of the internal organs.

In animal experiments and human observational studies, gut microflora and its composition have been demonstrated to have significant roles in body fat accumulation, and consequently, insulin resistance and obesity. The metabolic activity of …

Peroxisome Proliferator-Activated Receptor Δ Agonist Gw1516 Attenuates Diet-Induced Aortic Inflammation, Insulin Resistance, And Atherosclerosis In Low-Density Lipoprotein Receptor Knockout Mice, Lazar A. Bojic, Amy C. Burke, Sanjiv S. Chhoker, Dawn E. Telford, Brian G. Sutherland, Jane Y. Edwards, Cynthia G. Sawyez, Rommel G. Tirona, Hao Yin, J. Geoffrey Pickering, Murray W. Huff

Paediatrics Publications

OBJECTIVE - The peroxisome proliferator-activated receptor (PPAR) δ regulates systemic lipid homeostasis and inflammation. However, the ability of PPARδ agonists to improve the pathology of pre-established lesions and whether PPARδ activation is atheroprotective in the setting of insulin resistance have not been reported. Here, we examine whether intervention with a selective PPARδ agonist corrects metabolic dysregulation and attenuates aortic inflammation and atherosclerosis. APPROACH AND RESULTS - Low-density lipoprotein receptor knockout mice were fed a chow or a high-fat, high-cholesterol (HFHC) diet (42% fat, 0.2% cholesterol) for 4 weeks. For a further 8 weeks, the HFHC group was fed either HFHC …

Caspase-12 And Rheumatoid Arthritis In African-Americans, Laura Marshall, Mohammad Obaidullah, Trista Fuchs, Naomi S. Fineberg, Garland Brinkley, Ted R. Mikuls, Evan Hermel

Faculty Publications & Research of the TUC College of Osteopathic Medicine

CASPASE-12 (CASP12) has a downregulatory function during infection and thus may protect against inflammatory disease. We investigated the distribution of CASP12 alleles (#rs497116) in African-Americans (AA) with rheumatoid arthritis (RA). CASP12 alleles were genotyped in 953 RA patients and 342 controls. Statistical analyses comparing genotype groups were performed using Kruskal–Wallis non-parametric ANOVA with Mann–Whitney U tests and chi-square tests. There was no significant difference in the overall distribution of CASP12 genotypes within AA with RA, but CASP12 homozygous patients had lower baseline joint-narrowing scores. CASP12 homozygosity appears to be a subtle protective factor for some aspects of RA in AA …

Cervical Remodeling/Ripening At Term And Preterm Delivery: The Same Mechanism Initiated By Different Mediators And Different Effector Cells, Juan Miguel Gonzalez Velez

Wayne State University Dissertations

Premature cervical remodeling/ripening is believed to contribute to preterm delivery (PTD), the leading cause of perinatal morbidity and mortality. Despite considerable research, the causes of term and PTD remain unclear, and there is no effective treatment for PTD. We tested the hypothesis that complement activation plays a role in cervical remodeling and PTD. We studied cervical remodeling at term.

We studied two mouse models of inflammation-induced PTD. The first model was induced by vaginal administration of lipopolysaccharide (LPS)and the second one by administration of progesterone antagonist RU486. Increased cervical C3 deposition and macrophage infiltration and increased serum C3adesArg and C5adesArg …

Study Of Role Of Ribosomal Protein L13a In Resolving Inflammation, Darshana Poddar

ETD Archive

Inflammation is an obligatory attempt of the host immune system to protect the body against infection. However, unregulated synthesis of pro-inflammatory products can have detrimental effects. Though mechanisms which contribute to inflammation are well appreciated, those that resolve inflammation are poorly understood. Therefore, understanding the molecular basis of such pathways will provide an entirely novel approach to treat and prevent inflammatory diseases. Transcript-selective translational control can regulate the expression of a set of inflammatory genes. We have identified one such mechanism in a novel animal model which relies on the abrogation of ribosomal protein L13a-dependent translational silencing by creating macrophage-specific …

Effects Of Intermittent Pneumatic Compression On Delayed Onset Muscle Soreness (Doms) In Long Distance Runners, Shane N. Draper

ETD Archive

The purpose was to measure the effects of intermittent pneumatic compression (NormaTec, NT) on muscle inflammation after long distance running. Methods: Ten long distance runners, five males and five females, ages 18-55 years performed two, 20 mile runs at 70 VO2 max. The runs were followed by either no treatment (control) or NT treatment for five consecutive days. For the NT run, subjects were treated for one hour immediately following the run and daily for five days after. For the control run, subjects did not receive any treatment. Serum C - reactive protein (CRP), a marker of muscle inflammation, was …

Effect Of Tumor Necrosis Factorα On Expression Of Heme-Oxgenase1 In Human Gingival Fibroblasts, Jay Patel

PCOM Biomedical Studies Student Scholarship

Periodontitis is a chronic inflammatory disease that is characterized by activation of gingival fibroblasts to produce matrix metalloproteinases and other inflammatory mediators that contribute to destruction of tissues surrounding the teeth. In the United States, 22% of adults have a mild form of periodontal disease and 13% suffer from a severe form of the disease. In addition to tooth loss, periodontitis is associated with increased risk of several conditions, including diabetes, osteoporosis, rheumatoid arthritis and cardiovascular disease. Heme oxygenase-1 (HO-1) is activated by a wide variety of stressful stimuli and levels are increased in inflamed tissues. HO-1 degrades free heme, …

Effect Of Heme Oxygenase-1 On Matrix Metalloproteinase-3 Expression In Human Fibroblasts, Theresa A. Stangl

PCOM Biomedical Studies Student Scholarship

Heme oxygenase-1(HO-1) is an enzyme that plays a very important role in the resolution of inflammation. HO-1-based therapies are effective in a number of disease conditions. However, HO-1 also increases tumor growth, angiogenesis, metastasis and chemoresistance. Matrix metalloproteinase-3 (MMP-3) is an enzyme involved in physiological and pathophysiological tissue remodeling. Unbalanced expression of MMPs is a key feature of connective tissue destruction in chronic inflammatory conditions. Previously shown in this laboratory, the HO-1 inducer, hemin, increased MMP-3 mRNA expression in some HGF cultures. To assess whether HO-1 and/or its products regulate expression of MMP-3 in human fibroblasts, the effect of HO-1 …

Conservative Treatment Of De Quervain’S Tenosynovitis In Occupational Therapy: A Retrospective Outcome Study, Kevin R. Lang, Brittney S. Gibson, Kayleigh M. Oppenhuizen

Hand and Upper Extremity

Objective: De Quervain’s tenosynovitis (DQ) is a painful condition characterized by pain and inflammation at the first dorsal compartment of the wrist. This condition affects the wrist and thumb, and generally decreases an individual’s performance and engagement in daily occupations. Conservative management with occupational therapy (OT) can assist to diminish the associated symptoms and facilitate recovery of function; however, it is unclear what interventions are the most effective. The purpose of this study was to determine the effectiveness of conservative OT interventions for individuals diagnosed with DQ.

Study Design: An exploratory retrospective review of 148 de­‐identified electronic medical records provided …

The Molecular Mechanisms Underpinning The Therapeutic Properties Of Oleanolic Acid, Its Isomer And Derivatives For Type 2 Diabetes And Associated Complications, Danielle Camer, Yinghua Yu, Alexander Szabo, Xu-Feng Huang

Illawarra Health and Medical Research Institute

Recent research has uncovered the molecular mechanisms responsible for the therapeutic properties of oleanolic acid (OA), its isomer ursolic acid (UA), and derivatives. In particular, recent reports have highlighted the benefits of these compounds in the prevention and treatment of type 2 diabetes and associated life-threatening complications, such as nonalcoholic fatty liver disease, nephropathy, retinopathy, and atherosclerosis. The prevalence of type 2 diabetes is of major concern since it is reaching global epidemic levels. Treatments targeting the signaling pathways altered in type 2 diabetes are being actively investigated, and OA and UA in natural and derivative forms are potential candidates …

The Common Acid Sphingomyelinase Polymorphism P.G508r Is Associated With Self-Reported Allergy, Martin Reichel, Tanja Richter-Schmidinger, Christiane Muhle, Cosima Rhein, Panagiotis Alexopoulos, Sibylle G. Schwab, Erich Gulbins, Johannes Kornhuber

Illawarra Health and Medical Research Institute

Background: Acid sphingomyelinase (ASM) is a key regulator of ceramide-dependent signalling pathways. Among others, activation of ASM can be induced by CD95 or cytokine signalling and by cellular stress resulting from inflammation or infection. Increased ASM activity was observed in a variety of human diseases including inflammatory and neuropsychiatric disorders. We hypothesized that basal ASM activity might influence the susceptibility for common human diseases. Methods: The general health condition of 100 young people was assessed using a questionnaire. The ASM polymorphism rs1050239 (c.1522G>A; encoding p.G508R) was determined from genomic DNA. Activities of secretory (S-) and lysosomal (L-) ASM were …