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School of Medicine Faculty Publications

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Full-Text Articles in Investigative Techniques

Atypical Presentation Of Spindle Cell Lipoma In A Young Male With A History Of Malignant Melanoma, Ty Theriot, John David Cattar, Lacey Falgout, Nicholas Culotta, Christopher Haas Nov 2024

Atypical Presentation Of Spindle Cell Lipoma In A Young Male With A History Of Malignant Melanoma, Ty Theriot, John David Cattar, Lacey Falgout, Nicholas Culotta, Christopher Haas

School of Medicine Faculty Publications

Spindle cell lipoma (SCL) is a benign adipocytic tumor usually found in the subcutis of the posterior neck, upper back, and shoulder, predominantly in middle-aged males. This case report describes an atypical presentation of SCL in a 26-year-old male with a history of malignant melanoma. The patient presented with an erythematous plaque with central hyperpigmentation on the right upper arm, an uncommon location and presentation for SCL. Histopathological examination revealed an atypical myxoid spindle cell neoplasm with CD34 positivity and an overlying mildly atypical compound melanocytic nevus. The unusual clinical and histological features, combined with the patient's melanoma history, complicated …


Convexity Dural Hemangioma: Illustrative Case, Ellery A. Hayden, Jack A. Leoni, Frank Culicchia Nov 2024

Convexity Dural Hemangioma: Illustrative Case, Ellery A. Hayden, Jack A. Leoni, Frank Culicchia

School of Medicine Faculty Publications

BACKGROUND: Dural hemangiomas are a relatively rare form of intracranial mass, as hemangiomas tend to present in bone or as intraparenchymal lesions and only around 5%-13% have been reported to originate from the dura mater. Here, the authors present the case of a 46-year-old female who underwent craniotomy for a suspected convexity meningioma resection, which was unexpectedly found to be a dural capillary hemangioma. OBSERVATIONS: The patient was a 46-year-old female who presented with a left frontal intracranial mass found incidentally and showed significant growth over 4 years. The mass was suspected to be a meningioma as it was homogeneously …


Plasma Proteome Alterations Of Laying Hens Subjected To Heat Stress And Fed A Diet Supplemented With Pequi Oil (Caryocar Brasiliense Camb.): New Insights In The Identification Of Heat Stress Biomarkers, Joyce Da Silva, Luane Andrade, Paola Rodrigues, Laís Cordeiro, Gabrieli Lima, Júlia Lopes, Elis Castillo, Renata Martins, Andrey Assunção, José Vieira, Marília Busalaf, Jiri Adamec, José Sartori, Pedro Padilha Nov 2024

Plasma Proteome Alterations Of Laying Hens Subjected To Heat Stress And Fed A Diet Supplemented With Pequi Oil (Caryocar Brasiliense Camb.): New Insights In The Identification Of Heat Stress Biomarkers, Joyce Da Silva, Luane Andrade, Paola Rodrigues, Laís Cordeiro, Gabrieli Lima, Júlia Lopes, Elis Castillo, Renata Martins, Andrey Assunção, José Vieira, Marília Busalaf, Jiri Adamec, José Sartori, Pedro Padilha

School of Medicine Faculty Publications

Heat stress can disrupt the balance between the heat poultry release into the environment and the heat they generate. Pequi oil has antioxidant properties, which may mitigate the heat stress effects. This study aimed to investigate the response of laying hens to pequi oil supplementation under heat stress using a proteomic approach. A total of 96 Lohmann White laying hens with 26 weeks old were housed in a completely randomized design with a 2 × 2 factorial arrangement. They were housed in two climate chambers, thermal comfort temperature ± 24.04 °C with the relative humidity ± 66.35 and heat stress …


Molecular Architecture Of Chitin And Chitosan-Dominated Cell Walls In Zygomycetous Fungal Pathogens By Solid-State Nmr, Qinghui Cheng, Malitha C. Dickwella Widanage, Jayasubba Reddy Yarava, Ankur Ankur, Jean Paul Latgé, Ping Wang, Tuo Wang Sep 2024

Molecular Architecture Of Chitin And Chitosan-Dominated Cell Walls In Zygomycetous Fungal Pathogens By Solid-State Nmr, Qinghui Cheng, Malitha C. Dickwella Widanage, Jayasubba Reddy Yarava, Ankur Ankur, Jean Paul Latgé, Ping Wang, Tuo Wang

School of Medicine Faculty Publications

Zygomycetous fungal infections pose an emerging medical threat among individuals with compromised immunity and metabolic abnormalities. Our pathophysiological understanding of these infections, particularly the role of fungal cell walls in growth and immune response, remains limited. Here we conducted multidimensional solid-state NMR analysis to examine cell walls in five Mucorales species, including key mucormycosis causative agents like Rhizopus and Mucor species. We show that the rigid core of the cell wall primarily comprises highly polymorphic chitin and chitosan, with minimal quantities of β-glucans linked to a specific chitin subtype. Chitosan emerges as a pivotal molecule preserving hydration and dynamics. Some …


The Effectiveness Of The Gnana Laryngeal Mask Airway Ii (Gla-Ii) With Novel Suction Tubing In Gastrointestinal (Gi) Cases, Shahab Ahmadzadeh, Landyn D. Johnson, William T. Barham, James Ilochi, Matthew Fredericks, Giustino Varrassi, Sahar Shekoohi, Alan D. Kaye Sep 2024

The Effectiveness Of The Gnana Laryngeal Mask Airway Ii (Gla-Ii) With Novel Suction Tubing In Gastrointestinal (Gi) Cases, Shahab Ahmadzadeh, Landyn D. Johnson, William T. Barham, James Ilochi, Matthew Fredericks, Giustino Varrassi, Sahar Shekoohi, Alan D. Kaye

School of Medicine Faculty Publications

INTRODUCTION: The Gnana laryngeal mask airway II (GLA-II) is a supraglottic airway device similar to the classic laryngeal mask airway, except it has an additional suction port. This suction port allows for the removal of secretions and saliva. A previous version of the Gnana laryngeal airway 4 was made of silicone, while this newer version is made of polyvinyl chloride (PVC), which is more affordable. This study aimed to demonstrate the effectiveness and tolerability of this PVC-designed GLA-II and evaluate its ability to suction secretions. METHODS: The prospective cohort study included 100 gastrointestinal (GI) cases to determine the effectiveness and …


Roles Of Hydrogen Sulfide (H2s) As A Potential Therapeutic Agent In Cardiovascular Diseases: A Narrative Review, Kazi N. Islam, Ivan D. Nguyen, Rahib Islam, Humza Pirzadah, Hassan Malik Jul 2024

Roles Of Hydrogen Sulfide (H2s) As A Potential Therapeutic Agent In Cardiovascular Diseases: A Narrative Review, Kazi N. Islam, Ivan D. Nguyen, Rahib Islam, Humza Pirzadah, Hassan Malik

School of Medicine Faculty Publications

Cardiovascular disease (CVD) stands as one of the leading causes of morbidity and mortality worldwide, and the continued search for novel therapeutics is vital for addressing this global health challenge. Over the past decade, hydrogen sulfide (H₂S) has garnered significant attention in the field of medical research, as it has been proven to be a cardioprotective gaseous signaling molecule. It joins nitric oxide and carbon monoxide as endogenously produced gasotransmitters. As for its mechanism, H₂S functions through the posttranslational addition of a sulfur group to cysteine residues on target proteins in a process called sulfhydration. As a result, the observed …


Rare Causes Of Gastrointestinal Hemorrhage: A Case Series Of Adult Duodenal And Jejunal Gastric Heterotopia, Venkata Vinod Matli, John Kirkikis, Gregory Wellman, Dustin Hadley, Ross M. Dies, David F. Dies Jul 2024

Rare Causes Of Gastrointestinal Hemorrhage: A Case Series Of Adult Duodenal And Jejunal Gastric Heterotopia, Venkata Vinod Matli, John Kirkikis, Gregory Wellman, Dustin Hadley, Ross M. Dies, David F. Dies

School of Medicine Faculty Publications

Gastric heterotopia (GH) is a rare cause of gastrointestinal bleeding. GH of the small bowel is rare, and the duodenum is more commonly involved than the jejunum. Here, we present five cases of GH involving the duodenum and jejunum, with presentations including gastrointestinal bleeding, symptomatic anemia, and no symptoms. A 63-year-old man presented with melenic stools but could not identify an obvious bleeding source during endoscopy. He was ultimately diagnosed with jejunal GH. A 70-year-old woman with melena and severe anemia had a duodenal bulb mass detected during endoscopy, which was histopathologically diagnosed as GH. A 54-year-old woman experienced nausea, …


Bd Vaginal Panel Assay Results On The High-Throughput Bd Cor System Compared To The Bd Max System, Elizabeth Stonebraker, Wallace Greene, Stephanie N. Taylor, Catherine L. Cammarata, April Bobenchik, Elizabeth Lockamy Jun 2024

Bd Vaginal Panel Assay Results On The High-Throughput Bd Cor System Compared To The Bd Max System, Elizabeth Stonebraker, Wallace Greene, Stephanie N. Taylor, Catherine L. Cammarata, April Bobenchik, Elizabeth Lockamy

School of Medicine Faculty Publications

Molecular-based assays demonstrate excellent sensitivity for the detection of vaginitis causes. Here, the high-throughput BD Vaginal Panel for BD COR System (VP-COR) performance was compared to that of the predicate, BD MAX Vaginal Panel for BD MAX System (VP-MAX). Clinical or contrived samples were used to determine the agreement between VP-COR and VP-MAX. Acceptance criteria for VP-COR agreement were as follows: bacterial vaginosis (BV) required a positive percent agreement (PPA) point estimate of ≥ 95% and a negative percent agreement (NPA) point estimate of ≥ 98%; Candida group, Candida glabrata, Candida krusei, and Trichomonas vaginalis (TV) required a PPA and …


Clinical Trial Recruitment Of People Who Speak Languages Other Than English: A Children's Oncology Group Report, Melissa P. Beauchemin, Maria Ortega, Sheila J. Santacroce, Joanna M. Robles, Jenny Ruiz, Anurekha G. Hall, Justine M. Kahn, Cecilia Fu, Manuela Orjuela-Grimm, Grace C. Hillyer, Samrawit Solomon, Wendy Pelletier, Raul Montiel-Esparza, Lindsay J. Blazin, Cassie Kline, Alix E. Seif, Paula Aristizabal, Lena E. Winestone, Maria C. Velez Jun 2024

Clinical Trial Recruitment Of People Who Speak Languages Other Than English: A Children's Oncology Group Report, Melissa P. Beauchemin, Maria Ortega, Sheila J. Santacroce, Joanna M. Robles, Jenny Ruiz, Anurekha G. Hall, Justine M. Kahn, Cecilia Fu, Manuela Orjuela-Grimm, Grace C. Hillyer, Samrawit Solomon, Wendy Pelletier, Raul Montiel-Esparza, Lindsay J. Blazin, Cassie Kline, Alix E. Seif, Paula Aristizabal, Lena E. Winestone, Maria C. Velez

School of Medicine Faculty Publications

BACKGROUND: Persons who speak languages other than English are underrepresented in clinical trials, likely in part because of inadequate multilevel resources. We conducted a survey of institutions affiliated with the Children's Oncology Group (COG) to characterize current research recruitment practices and resources regarding translation and interpretation services. METHODS: In October 2022, a 20-item survey was distributed electronically to institutions affiliated with COG to assess consent practices and resources for recruiting participants who speak languages other than English to COG trials. Descriptive statistics were used to summarize responses; responses were compared by institution size and type as well as respondent role. …


An Exploratory Analysis Of Sociodemographic Factors Associated With Physical Functional Impairment In Icu Survivors, Megan A. Watson, Marie Sandi, Johanna Bixby, Grace Perry, Patrick J. Offner, Ellen L. Burnham, Sarah E. Jolley Jun 2024

An Exploratory Analysis Of Sociodemographic Factors Associated With Physical Functional Impairment In Icu Survivors, Megan A. Watson, Marie Sandi, Johanna Bixby, Grace Perry, Patrick J. Offner, Ellen L. Burnham, Sarah E. Jolley

School of Medicine Faculty Publications

IMPORTANCE: Physical functional impairment is one of three components of postintensive care syndrome (PICS) that affects up to 60% of ICU survivors. OBJECTIVES: To explore the prevalence of objective physical functional impairment among a diverse cohort of ICU survivors, both at discharge and longitudinally, and to highlight sociodemographic factors that might be associated with the presence of objective physical functional impairment. DESIGN, SETTING, AND PARTICIPANTS: This was a secondary analysis of 37 patients admitted to the ICU in New Orleans, Louisiana, and Denver, Colorado between 2016 and 2019 who survived with longitudinal follow-up data. MAIN OUTCOMES AND MEASURES: Our primary …


Probability Of Occult Ankle Fracture Based On Radiograph-Measured Swelling, Christian Kenneth Kerut, Srikanth Mudiganty, Denise Goodfellow Kerut, Ronald L. Horswell, Reagan Williams, Melanie Valencia, Joseph Gonzales May 2024

Probability Of Occult Ankle Fracture Based On Radiograph-Measured Swelling, Christian Kenneth Kerut, Srikanth Mudiganty, Denise Goodfellow Kerut, Ronald L. Horswell, Reagan Williams, Melanie Valencia, Joseph Gonzales

School of Medicine Faculty Publications

INTRODUCTION: Pediatric ankle injuries are a common presentation in the emergency department (ED). A quarter of pediatric ankle fractures show no radiographic evidence of a fracture. Physicians often correlate non-weight bearing and tenderness with an occult fracture. We present this study to predict the probability of an occult fracture using radiographic soft-tissue swelling on initial ED radiographs. METHODS: This is a retrospective study at a Level 1 pediatric trauma center from 2021 to 22. Soft-tissue swelling between the lateral malleolus and skin was measured on radiographs, and weight-bearing status was documented. Statistical analysis was conducted using Stata software. DISCUSSION: The …


Vitamin D Deficiency In Scheuermann's Disease Is Associated With Increased Adverse Outcomes, Shivan N. Chokshi, Srikanth Mudiganty, Rutledge Carter Clement, William Accousti Apr 2024

Vitamin D Deficiency In Scheuermann's Disease Is Associated With Increased Adverse Outcomes, Shivan N. Chokshi, Srikanth Mudiganty, Rutledge Carter Clement, William Accousti

School of Medicine Faculty Publications

INTRODUCTION: Scheuermann's disease is a diagnosis of hyperkyphosis commonly encountered in pediatric patients. Studies in animal models suggest an association with vitamin D deficiency, however, extensive studies have not been performed in humans. This study analyzes the role of vitamin D deficiency on unfavorable results in patients with Scheuermann's disease. METHODS: The TriNetX database was utilized to perform a retrospective analysis. Patients in the United States aged 0-18 years with Scheuermann's disease were identified using International Classification of Diseases, Tenth Revision (ICD-10) codes and categorized into those with and without a diagnosis of vitamin D deficiency. Comparison of patient groups …


Conceptualizing Care Partners' Burden, Stress, And Support For Reintegrating Veterans: A Mixed Methods Study, Nicholas A. Rattray, Mindy Flanagan, Allison Mann, Leah Danson, Ai-Nghia Do, Diana Natividad, Katrina Spontak, Gala True Feb 2024

Conceptualizing Care Partners' Burden, Stress, And Support For Reintegrating Veterans: A Mixed Methods Study, Nicholas A. Rattray, Mindy Flanagan, Allison Mann, Leah Danson, Ai-Nghia Do, Diana Natividad, Katrina Spontak, Gala True

School of Medicine Faculty Publications

BACKGROUND: People who support Veterans as they transition from their military service into civilian life may be at an increased risk of psychological distress. Existing studies focus primarily on paid family caregivers, but few studies include spouses and informal non-family "care partners." We sought to identify key challenges faced by care partners of Veterans with invisible injuries. METHODS: Semi-structured interviews were conducted with 36 individuals involved in supporting a recently separated US military Veteran enrolled in a 2-year longitudinal study. CPs completed validated measures on perceived stress, caregiving burden, quality of their relationship, life satisfaction, and flourishing. Independent -tests were …


Amondys 45 (Casimersen), A Novel Antisense Phosphorodiamidate Morpholino Oligomer: Clinical Considerations For Treatment In Duchenne Muscular Dystrophy, Megan E. Vasterling, Rebecca J. Maitski, Brice A. Davis, Julie E. Barnes, Rucha A. Kelkar, Rachel J. Klapper, Hirni Patel, Shahab Ahmadzadeh, Sahar Shekoohi, Alan D. Kaye, Giustino Varrassi Dec 2023

Amondys 45 (Casimersen), A Novel Antisense Phosphorodiamidate Morpholino Oligomer: Clinical Considerations For Treatment In Duchenne Muscular Dystrophy, Megan E. Vasterling, Rebecca J. Maitski, Brice A. Davis, Julie E. Barnes, Rucha A. Kelkar, Rachel J. Klapper, Hirni Patel, Shahab Ahmadzadeh, Sahar Shekoohi, Alan D. Kaye, Giustino Varrassi

School of Medicine Faculty Publications

AMONDYS 45 (casimersen) is an antisense oligonucleotide therapy used to treat Duchenne muscular dystrophy (DMD), a rare genetic disorder characterized by a mutation in the DMD gene. Symptoms include progressive muscle weakness, respiratory and cardiac complications, and premature death. Casimersen targets a specific mutation in the DMD gene that results in the absence of dystrophin protein, a key structural component of muscle fibers. While there is currently no cure for DMD, exon-skipping therapy works by restoring the reading frame of the mutated gene, allowing the production of a partially functional dystrophin protein. Clinical trials of casimersen have shown promising results …


Incidence Of Rapidly Progressive Osteoarthritis Following Intra-Articular Hip Corticosteroid Injection: A Systematic Review And Meta-Analysis, Franco M. Sabatini, Anna Cohen-Rosenblum, Travis B. Eason, Charles P. Hannon, Samuel D. Mounce, Chad A. Krueger, F Winston Gwathmey, Stephen T. Duncan, David C. Landy Dec 2023

Incidence Of Rapidly Progressive Osteoarthritis Following Intra-Articular Hip Corticosteroid Injection: A Systematic Review And Meta-Analysis, Franco M. Sabatini, Anna Cohen-Rosenblum, Travis B. Eason, Charles P. Hannon, Samuel D. Mounce, Chad A. Krueger, F Winston Gwathmey, Stephen T. Duncan, David C. Landy

School of Medicine Faculty Publications

BACKGROUND: The American Academy of Orthopedic Surgery recommends intra-articular corticosteroid injections (CSIs) for managing hip osteoarthritis (OA) based on short-term, prospective studies. Recent retrospective studies have raised concerns that CSIs may lead to rapidly progressive OA (RPOA). We sought to systematically review the literature of CSIs for hip OA to estimate the incidence of RPOA. METHODS: MEDLINE, Embase, and Cochrane Library were searched to identify original research of hip OA patients receiving CSIs. Overall, 27 articles involving 5831 patients published from 1988 to 2022 were included. Study design, patient characteristics, CSI details, follow-up, and cases of RPOA were recorded. Studies …


Rod-Specific Downregulation Of Omega-3 Very-Long-Chain Polyunsaturated Fatty Acid Pathway In Age-Related Macular Degeneration, William C. Gordon, Marie Audrey I. Kautzmann, Bokkyoo Jun, Megan L. Cothern, Zhide Fang, Nicolas G. Bazan Sep 2023

Rod-Specific Downregulation Of Omega-3 Very-Long-Chain Polyunsaturated Fatty Acid Pathway In Age-Related Macular Degeneration, William C. Gordon, Marie Audrey I. Kautzmann, Bokkyoo Jun, Megan L. Cothern, Zhide Fang, Nicolas G. Bazan

School of Medicine Faculty Publications

Docosahexaenoic acid (DHA; 22:6) plays a key role in vision and is the precursor for very-long-chain polyunsaturated fatty acids (VLC-PUFAs). The release of 32- and 34-carbon VLC-PUFAs and DHA from sn-1 and sn-2 of phosphatidylcholine (PC) leads to the synthesis of cell-survival mediators, the elovanoids (ELVs) and neuroprotectin D1 (NPD1), respectively. Macula and periphery from age-related macular degeneration (AMD) donor retinas were assessed for the availability of DHA-related lipids by LC-MS/MS-based lipidomic analysis and MALDI-molecular imaging. We found reduced retina DHA and VLC-PUFA pathways to synthesize omega-3 ELVs from precursors that likely resulted in altered disks and photoreceptor loss. Additionally, …


A Matched Cohort Study Of Open Thoracostomies Performed By Ground Medics, Alison Smith, Angelo Ciaraglia, Benjamin Axtman, Cj Winckler, David Wampler, Maxwell Braverman, C. Patrick Shahan, Rachelle Babbitt Jonas, Michael Shiels, Brian Eastridge, Ronald Stewart, Susannah Nicholson, Donald Jenkins Apr 2023

A Matched Cohort Study Of Open Thoracostomies Performed By Ground Medics, Alison Smith, Angelo Ciaraglia, Benjamin Axtman, Cj Winckler, David Wampler, Maxwell Braverman, C. Patrick Shahan, Rachelle Babbitt Jonas, Michael Shiels, Brian Eastridge, Ronald Stewart, Susannah Nicholson, Donald Jenkins

School of Medicine Faculty Publications

Background: Tension pneumothorax resulting from chest trauma is a rapidly fatal condition that requires prompt treatment. Prehospital open thoracostomy (POT) is a potentially lifesaving intervention that can be performed in the field to treat tension pneumothorax. However, the results from POT performed by ground EMS providers have not been well-studied. The objective of this study was to compare outcomes for patients with chest trauma who underwent POT performed by ground EMS providers with a matched cohort who did not undergo this procedure in the field. Methods: A retrospective chart review of consecutive adult patients presenting to a Level I trauma …


Diagnostic Performance Of Afirma And Interpace Diagnostics Genetic Testing In Indeterminate Thyroid Nodules: A Single Center Study †, Emad Kandil, Tyler A. Metz, Peter P. Issa, Mohamed Aboueisha, Mahmoud Omar, Abdallah S. Attia, Bert Chabot, Mohammad Hussein, Krzysztof Moroz, Mohamed Shama, Eman Toraih Mar 2023

Diagnostic Performance Of Afirma And Interpace Diagnostics Genetic Testing In Indeterminate Thyroid Nodules: A Single Center Study †, Emad Kandil, Tyler A. Metz, Peter P. Issa, Mohamed Aboueisha, Mahmoud Omar, Abdallah S. Attia, Bert Chabot, Mohammad Hussein, Krzysztof Moroz, Mohamed Shama, Eman Toraih

School of Medicine Faculty Publications

Indeterminate thyroid nodules (ITN) represent 20–30% of biopsied nodules, with a 10–60% risk of malignancy. Molecular testing can stratify the risk of malignancy among ITNs, and subsequently reduce the need for unnecessary diagnostic surgery. We aimed to assess the performance of these molecular tests at a single institution. Patients with Bethesda III, IV, and V nodules with Afirma and Interpace Diagnostics genetic testing data from November 2013 to November 2021 were included. Three cohorts were formed, including GSC + XA, ThyGeNEXT + ThyraMIR, and GSC + GEC. Statistical analysis determined the sensitivity, specificity, positive predictive value (PPV), negative predictive value …


Magnetic Resonance Imaging-Derived Microvascular Perfusion Modeling To Assess Peripheral Artery Disease, Olga A. Gimnich, Tatiana Belousova, Christina M. Short, Addison A. Taylor, Vijay Nambi, Joel D. Morrisett, Christie M. Ballantyne, Jean Bismuth, Dipan J. Shah, Gerd Brunner Jan 2023

Magnetic Resonance Imaging-Derived Microvascular Perfusion Modeling To Assess Peripheral Artery Disease, Olga A. Gimnich, Tatiana Belousova, Christina M. Short, Addison A. Taylor, Vijay Nambi, Joel D. Morrisett, Christie M. Ballantyne, Jean Bismuth, Dipan J. Shah, Gerd Brunner

School of Medicine Faculty Publications

BACKGROUND: Computational fluid dynamics has shown good agreement with contrast-enhanced magnetic resonance imaging measurements in cardiovascular disease applications. We have developed a biomechanical model of microvascular perfusion using contrast-enhanced magnetic resonance imaging signal intensities derived from skeletal calf muscles to study peripheral artery disease (PAD). METHODS AND RESULTS: The computational microvascular model was used to study skeletal calf muscle perfusion in 56 in-dividuals (36 patients with PAD, 20 matched controls). The recruited participants underwent contrast-enhanced magnetic resonance imaging and ankle-brachial index testing at rest and after 6-minute treadmill walking. We have determined associations of microvascular model parameters including the transfer …


Helical Remodeling Augments 5-Lipoxygenase Activity In The Synthesis Of Proinflammatory Mediators, Eden M. Gallegos, Tanner D. Reed, Forge A. Mathes, Nelson V. Guevara, David B. Neau, Wei Huang, Marcia E. Newcomer, Nathaniel C. Gilbert Sep 2022

Helical Remodeling Augments 5-Lipoxygenase Activity In The Synthesis Of Proinflammatory Mediators, Eden M. Gallegos, Tanner D. Reed, Forge A. Mathes, Nelson V. Guevara, David B. Neau, Wei Huang, Marcia E. Newcomer, Nathaniel C. Gilbert

School of Medicine Faculty Publications

The synthesis of proinflammatory leukotrienes implicated in asthma, allergic rhinitis, and atherosclerosis is initiated by the enzyme 5-lipoxygenase (5-LOX). The crystal structure of human Stable-5-LOX revealed a conformation where the catalytic iron was inaccessible to bulk solvent as two aromatic residues on a conserved helix-α2 (Hα2) plugged the substrate access portal. Whether 5-LOX can also adopt a more open conformation has not been resolved. Here, we present a new conformation of 5-LOX where Hα2 adopts an elongated conformation equivalent to that described in other animal lipoxygenase structures. Our observation of the sigmoidal kinetic behavior of 5-LOX, which is indicative of …