Immunopathology Commons^™

Structure And Funding Of Clinical Informatics Fellowships: A National Survey Of Program Directors, Tushar N Patel, Aaron J Chaise, John J Hanna, Kunal P Patel, Karl M Kochendorfer, Richard J Medford, Dara E Mize, Edward R Melnick, Jonathan D Hron, Kenneth Youens, Deepti Pandita, Michael G Leu, Gregory A Ator, Feliciano Yu, Nicholas Genes, Carrie K Baker, Douglas S Bell, Joshua M Pevnick, Steven A Conrad, Aarti R Chandawarkar, Kendall M Rogers, David C Kaelber, Ila R Singh, Bruce P Levy, John T Finnell, Joseph Kannry, Natalie M Pageler, Vishnu Mohan, Christoph U Lehmann

Faculty, Staff and Students Publications

BACKGROUND: In 2011, the American Board of Medical Specialties established clinical informatics (CI) as a subspecialty in medicine, jointly administered by the American Board of Pathology and the American Board of Preventive Medicine. Subsequently, many institutions created CI fellowship training programs to meet the growing need for informaticists. Although many programs share similar features, there is considerable variation in program funding and administrative structures.

OBJECTIVES: The aim of our study was to characterize CI fellowship program features, including governance structures, funding sources, and expenses.

METHODS: We created a cross-sectional online REDCap survey with 44 items requesting information on program administration, …

Bridging The Gap: Assessing Cmv Dnaemia In Kidney Transplant Recipients With Previous Solid Organ Transplants, Goni Katz-Greenberg, Julie M Steinbrink, Krishna Shah, Jennifer S Byrns

Faculty, Staff and Students Publications

Cytomegalovirus (CMV) infection poses a significant threat to solid organ transplant (SOT) recipients and can lead to various complications and adverse outcomes. In an effort to prevent CMV infection, it is common to utilize prophylactic strategies, including antiviral medications such as valganciclovir, especially for high-risk patients. Risk factors for CMV infection in kidney transplant recipients (KTRs) include CMV mismatch between donor and recipient (i.e., donor positive, recipient negative), and intensity of immunosuppression, such as the use of T-cell depleting agents. However, little attention has been given to KTRs with a history of prior SOTs, despite their prolonged exposure to immunosuppressive …

Translational And Oncologic Significance Of Tertiary Lymphoid Structures In Pancreatic Adenocarcinoma, Zachary Gao, Joseph Azar, Huili Zhu, Sophia Williams-Perez, Sung Wook Kang, Celia Marginean, Mark P Rubinstein, Shalini Makawita, Hyun-Sung Lee, E Ramsay Camp

Faculty, Staff and Students Publications

Pancreatic adenocarcinoma (PDAC) is an aggressive tumor with poor survival and limited treatment options. PDAC resistance to immunotherapeutic strategies is multifactorial, but partially owed to an immunosuppressive tumor immune microenvironment (TiME). However, the PDAC TiME is heterogeneous and harbors favorable tumor-infiltrating lymphocyte (TIL) populations. Tertiary lymphoid structures (TLS) are organized aggregates of immune cells that develop within non-lymphoid tissue under chronic inflammation in multiple contexts, including cancers. Our current understanding of their role within the PDAC TiME remains limited; TLS are complex structures with multiple anatomic features such as location, density, and maturity that may impact clinical outcomes such as …

Childhood And Adolescent Relapsed/Refractory Aggressive B-Cell Lymphomas With T(8;14) And Bcl2 Expression, Burkitt Lymphoma Versus Diffuse Large B-Cell Lymphoma: A Diagnostic Challenge, Fouad El Dana, Sofia Alexandra Garces Narvaez, Nader K El-Mallawany, Jennifer E Agrusa, Zoann E Dreyer, Andrea N Marcogliese, Mohamed Tarek Elghetany, Jyotinder N Punia, Chi Young Ok, Keyur P Patel, Dolores H Lopez-Terrada, Kevin E Fisher, Choladda V Curry

Faculty, Staff and Students Publications

We present 2 diagnostically challenging cases of pediatric/adolescent relapsed/refractory aggressive mature B-cell non-Hodgkin lymphoma (B-NHL) within the spectrum of Burkitt lymphoma and diffuse large B-cell lymphoma and illustrate the different therapeutic regimens that are employed for pediatric and adult cancer centers. Both cases displayed varying-sized lymphoma cells with occasional single prominent nucleoli and heterogeneous BCL2 expression. Cytogenetics revealed complex karyotypes with t(8:14)(q24.2;q32) and IGH::MYC rearrangement by FISH. Next generation sequencing revealed deleterious TP53 and MYC mutations. We concluded that both could be diagnosed as “DLBCL-NOS with MYC rearrangement” using the current pathologic classifications, 2022 International Consensus Classification (ICC) and World …

Highly Invasive Biliary Cancer Presenting As Multiple Extrabiliary Lesions Masquerading As Abscesses, Alexander Lu, Alireza Mojtahedi, Lukman Cheraghvandi, David Wynne, Neda Zarrin-Khameh, Mohammad Ghasemi Rad

Faculty, Staff and Students Publications

Carcinosarcomas of the biliary tract are an extremely rare type of malignancy and may be low on a differential when presenting as multiple metastatic masses. In this case report, we report a case of a female who presented with an aggressive late-stage disease whose initial workup did not indicate a malignant process. Further complicating her care, biopsy samples taken from extra-hepatic masses were culture-positive for Lactobacillus rhamnosu. Given the late stage of the patient’s disease, hospice care was initiated. The patient passed away four months after the initial presentation.

Invasive Community-Onset Gram-Positive Infections From July 2018 Through December 2022 At 2 Children's Hospitals, Eric E Engstrom, Alexander S Plattner, J Chase Mcneil, Kristina G Hulten, Patrick J Reich, Mary G Boyle, James J Dunn, Stephanie A Fritz, Sheldon L Kaplan

Faculty, Staff and Students Publications

BACKGROUND: Invasive infections caused by Streptococcus pyogenes (invasive group A streptococcus [iGAS]) and Streptococcus pneumoniae (invasive pneumococcal disease [IPD]) decreased substantially at the beginning of the COVID-19 pandemic. Our study sought to evaluate the extent of this decrease and the trends of these infections since reversion of societal adjustments incident to the pandemic. We also wanted to compare the frequency of these infections with invasive community-onset Staphylococcus aureus (I-CO-SA) infections and common respiratory viral infections in this period.

METHODS: Cases of iGAS, IPD, and I-CO-SA infections were identified prospectively and retrospectively at 2 large US children's hospitals by positive cultures …

Best Practices For Effective Management Of Point Of Care Testing, Anil K Chokkalla, Brandy D Recio, Sridevi Devaraj

Faculty, Staff and Students Publications

With the recent COVID-19 pandemic, point-of-care testing has gained tremendous attention, particularly in acute care settings. The point-of-care testing landscape is rapidly expanding and being contemplated for any crucial test with a central laboratory turnaround time >25% of the clinical decision time. A typical point-of-care testing program within a large hospital system encompasses a multitude of operators utilizing a wide range of devices across multiple testing sites. Thus, managing a large point-of-care testing network remains a daunting task with challenges related to staffing, standardization, quality management, training and competency assessment, and data management. This review will focus on understanding the …

Polygenic Genetic Variation Affecting Antibody Formation Underlies Hypertensive Renal Injury In The Stroke-Prone Spontaneously Hypertensive Rat, Isha S Dhande, Yaming Zhu, Aniket S Joshi, M John Hicks, Michael C Braun, Peter A Doris

Faculty, Staff and Students Publications

During development of the spontaneously hypertensive rat (SHR), several distinct but closely related lines were generated. Most lines are resistant to hypertensive renal disease. However, the SHR-A3 line (stroke-prone SHR) experiences end-organ injury (EOI) and provides a model of injury susceptibility that can be used to uncover genetic causation. In the present study, we generated a congenic line in which three distinct disease loci in SHR-A3 are concurrently replaced with homologous loci from an injury-resistant SHR line (SHR-B2). Verification that all three loci were homozygously replaced in this triple congenic line [SHR-A3(Trip B2)] while the genetic background of SHR-A3 was …

Unexpected Drug-Induced Liver Injury Associated With Menofit: A Synbiotic Menopause Supplement, Apaar Dadlani, Azubuogu Anudu, E Celia Marginean

Faculty, Staff and Students Publications

MenoFit is a widely available over-the-counter synbiotic supplement, which is marketed for use in relieving menopausal symptoms. So far, there is no published data on liver injury because of its use. We present the first reported case of MenoFit-induced liver injury in a patient who presented with 1 week of jaundice and abnormal liver biochemical tests in the absence of other risk factors and negative comprehensive workup for known etiologies of liver disease.

Stratification Of Pediatric Covid-19 Cases Using Inflammatory Biomarker Profiling And Machine Learning., Devika Subramanian, Aadith Vittala, Xinpu Chen, Christopher Julien, Sebastian Acosta, Craig Rusin, Carl Allen, Nicholas Rider, Zbigniew Starosolski, Ananth Annapragada, Sridevi Devaraj

Faculty, Staff and Students Publications

While pediatric COVID-19 is rarely severe, a small fraction of children infected with SARS-CoV-2 go on to develop multisystem inflammatory syndrome (MIS-C), with substantial morbidity. An objective method with high specificity and high sensitivity to identify current or imminent MIS-C in children infected with SARS-CoV-2 is highly desirable. The aim was to learn about an interpretable novel cytokine/chemokine assay panel providing such an objective classification. This retrospective study was conducted on four groups of pediatric patients seen at multiple sites of Texas Children's Hospital, Houston, TX who consented to provide blood samples to our COVID-19 Biorepository. Standard laboratory markers of …

Comparison Of Random Urine Protein/Creatinine Ratio With 24-Hour Urine Protein In Suspected Pre-Eclampsia, Lily Olayinka, Emily Garnett, Brian Burnett, Sridevi Devaraj

Faculty, Staff and Students Publications

INTRODUCTION: Proteinuria is one of the classical criteria for the diagnosis of pre-eclampsia. The gold standard remains the measurement of 24-h urine protein which is time consuming and prone to preanalytical errors. Random urine protein creatinine ratio (UPCR) is endorsed by clinical practice guidelines as a faster alternative. The aim of this study was to evaluate the correlation between the 24-h urine protein excretion and UPCR in the identification of proteinuria in suspected preeclamptic patients.

METHOD: A total of 51 women with suspected pre-eclampsia from the maternal fetal clinic of our institution were retrospectively studied. The correlation between the UPCR …

The Role Of Fas Receptor Methylation In Osteosarcoma Metastasis, Jiayi M Sun, Wing-Yuk Chow, Gufeng Xu, M John Hicks, Manjula Nakka, Jianhe Shen, Patrick Kwok Shing Ng, Aaron M Taylor, Alexander Yu, Jason E Farrar, Donald A Barkauskas, Richard Gorlick, Jaime M Guidry Auvil, Daniela Gerhard, Paul Meltzer, Rudy Guerra, Tsz-Kwong Man, Ching C Lau, On Behalf Of The Target Osteosarcoma Consortium

Faculty, Staff and Students Publications

Osteosarcoma is the most frequent primary malignant bone tumor with an annual incidence of about 400 cases in the United States. Osteosarcoma primarily metastasizes to the lungs, where FAS ligand (FASL) is constitutively expressed. The interaction of FASL and its cell surface receptor, FAS, triggers apoptosis in normal cells; however, this function is altered in cancer cells. DNA methylation has previously been explored as a mechanism for altering FAS expression, but no variability was identified in the CpG island (CGI) overlapping the promoter. Analysis of an expanded region, including CGI shores and shelves, revealed high variability in the methylation of …

Pediatric Vitamin D: Pseudo-Hypervitaminosis, Lily Olayinka, Izmarie Poventud-Fuentes, Emily Garnett, Sridevi Devaraj

Faculty, Staff and Students Publications

BACKGROUND: Vitamin D toxicity is rare in pediatric population. Falsely elevated levels of 25-hydroxyvitamin D have been reported as a major challenge with immunoassay methods for quantifying vitamin D metabolites.

CASE PRESENTATION AND METHOD: Here, we present two pediatric cases of falsely elevated 25-hydroxyvitamin D that resulted in unnecessary further testing. We also report significant same-day variation in the measurement of 25-hydroxyvitamin D using the Abbott i2000SR immunoassay. Samples were spun twice and their values were confirmed with the gold standard liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for confirmation.

CONCLUSION: The addition of a centrifugation step prior to sample testing …

Barriers To A Successful Healthcare Transition For Individuals With Urea Cycle Disorders, Farah A Ladha, Cynthia Le Mons, William J Craigen, Pilar L Magoulas, Ronit Marom, Andrea M Lewis

Faculty, Staff and Students Publications

The pediatric to adult healthcare transition (HCT) is a process for individuals with chronic health conditions to gradually shift from a pediatric to an adult-oriented care system. Autonomy and self-management skills required for an individual's HCT readiness can be evaluated through the transition readiness assessment questionnaire (TRAQ). Despite general HCT preparation guidelines, little is known about the HCT experience of individuals with a urea cycle disorder (UCD). This is the first study to report the parent or guardian perception of the HCT process in children with a UCD by investigating the stages of transition readiness and transition outcome. We identify …

The Role Of Limch1 Alternative Splicing In Skeletal Muscle Function, Matthew S Penna, Rong-Chi Hu, George G Rodney, Thomas A Cooper

Faculty, Staff and Students Publications

Postnatal skeletal muscle development is a highly dynamic period associated with widespread alternative splicing changes required to adapt tissues to adult function. These splicing events have significant implications because the reversion of adult mRNA isoforms to fetal isoforms is observed in forms of muscular dystrophy. LIMCH1 is a stress fiber–associated protein that is alternatively spliced to generate uLIMCH1, a ubiquitously expressed isoform, and mLIMCH1, a skeletal muscle–specific isoform containing six additional exons simultaneously included after birth in the mouse. CRISPR/Cas9 was used to delete the six alternatively spliced exons of LIMCH1 in mice, thereby forcing the constitutive expression of the …

An Ocular Th1 Immune Response Promotes Corneal Nerve Damage Independently Of The Development Of Corneal Epitheliopathy, Alexia Vereertbrugghen, Manuela Pizzano, Florencia Sabbione, Irene Angelica Keitelman, Carolina Maiumi Shiromizu, Douglas Vera Aguilar, Federico Fuentes, Cintia S De Paiva, Mirta Giordano, Analía Trevani, Jeremías G Galletti

Faculty, Staff and Students Publications

Proper sight is not possible without a smooth, transparent cornea, which is highly exposed to environmental threats. The abundant corneal nerves are interspersed with epithelial cells in the anterior corneal surface and are instrumental to corneal integrity and immunoregulation. Conversely, corneal neuropathy is commonly observed in some immune-mediated corneal disorders but not in others, and its pathogenesis is poorly understood. Here we hypothesized that the type of adaptive immune response may influence the development of corneal neuropathy. To test this, we first immunized OT-II mice with different adjuvants that favor T helper (Th)1 or Th2 responses. Both Th1-skewed mice (measured …

Fine Needle Aspiration Of Pancreatic Lesions Focusing On Secondary Tumors With Emphasis Of Metastatic Breast Cancer: A Clinicopathological Study With Follow-Up, Maria Yanqing Chen, Neda Zarrin-Khameh, Ya Xu

Faculty, Staff and Students Publications

BACKGROUND: The data on metastatic tumors to the pancreas diagnosed by fine needle aspiration (FNA) biopsy is limited. We report our experience of FNA of primary and secondary pancreatic tumors emphasizing metastatic breast cancer in the pancreas.

METHOD: Total 274 cases of pancreatic FNA in 10 years were retrospectively reviewed. Literature review of metastatic breast cancers to the pancreas was performed.

RESULTS: Out of the 274 cases, 7 (7/274, 2.6%) cases were non-diagnostic, 46 (46/274, 16.8%) cases were negative for malignancy, and 40 (40/274, 14.6%) cases were under the category of atypical cells. There were 133 (133/274, 48.5%) cases diagnosed …

Urinary Cd163 Is A Marker Of Active Kidney Disease In Childhood-Onset Lupus Nephritis, Haleigh Inthavong, Kamala Vanarsa, Jessica Castillo, M John Hicks, Chandra Mohan, Scott E Wenderfer

Faculty, Staff and Students Publications

OBJECTIVE: The objective of this study was to evaluate the utility of urine CD163 for detecting disease activity in childhood-onset SLE (cSLE) patients.

METHODS: Sixty consecutive pediatric patients fulfilling four or more ACR criteria for SLE and 20 healthy controls were recruited for testing of urinary CD163 using ELISA. SLE disease activity was assessed using the SLEDAI-2K.

RESULTS: Urine CD163 was significantly higher in patients with active LN than inactive SLE patients and healthy controls, with receiver operating characteristics area under the curve values ranging from 0.93 to 0.96. LN was ascertained by kidney biopsy. Levels of CD163 significantly correlated …

Corrigendum To 'The Hemophilia Joint Health Score Version 21 Validation In Adult Patients Study: A Multicenter International Study' [Research And Practice In Thrombosis And Haemostasis, 6/2, (2022) E12690], Adrian Minford, Leonardo R Brand Ao, Maha Othman, Christoph Male, Rezan Abdul-Kadir, Paul Monagle, Andrew D Mumford, Dorothy Adcock, Björn Dahlbäck, Predrag Miljic, Maria T Desancho, Jun Teruya

Faculty, Staff and Students Publications

This corrects the article "The Hemophilia Joint Health Score version 2.1 Validation in Adult Patients Study: A multicenter international study" in volume 6, e12690.

Alternative Splicing Mediates The Compensatory Upregulation Of Mbnl2 Upon Mbnl1 Loss-Of-Function, Larissa Nitschke, Rong-Chi Hu, Andrew N Miller, Lathan Lucas, Thomas A Cooper

Faculty, Staff and Students Publications

Loss of gene function can be compensated by paralogs with redundant functions. An example of such compensation are the paralogs of the Muscleblind-Like (MBNL) family of RNA-binding proteins that are sequestered and lose their function in Myotonic Dystrophy Type 1 (DM1). Loss of MBNL1 increases the levels of its paralog MBNL2 in tissues where Mbnl2 expression is low, allowing MBNL2 to functionally compensate for MBNL1 loss. Here, we show that loss of MBNL1 increases the inclusion of Mbnl2 exon 6 and exon 9. We find that inclusion of Mbnl2 exon 6 increases the translocation of MBNL2 to the nucleus, while …

Insights Into Cell-Specific Functions Of Microtubules In Skeletal Muscle Development And Homeostasis, Lathan Lucas, Thomas A Cooper

Faculty, Staff and Students Publications

The contractile cells of skeletal muscles, called myofibers, are elongated multinucleated syncytia formed and maintained by the fusion of proliferative myoblasts. Human myofibers can be hundreds of microns in diameter and millimeters in length. Myofibers are non-mitotic, obviating the need for microtubules in cell division. However, microtubules have been adapted to the unique needs of these cells and are critical for myofiber development and function. Microtubules in mature myofibers are highly dynamic, and studies in several experimental systems have demonstrated the requirements for microtubules in the unique features of muscle biology including myoblast fusion, peripheral localization of nuclei, assembly of …

Growth And Differentiation Factor 15 (Gdf15) Levels Predict Adverse Respiratory Outcomes In Premature Neonates, Faeq Almudares, Joseph Hagan, Xinpu Chen, Sridevi Devaraj, Bhagavatula Moorthy, Krithika Lingappan

Faculty, Staff and Students Publications

Growth and differentiation factor 15 (GDF15) is a stress-responsive cytokine, and its expression increases during inflammation, hyperoxia, and senescence. Significantly, GDF15 is secreted by the placenta, and maternal levels increase throughout pregnancy. Serum GDF15 level is a promising biomarker for many lung diseases like pulmonary hypertension and pulmonary fibrosis. However, circulating GDF15 levels in preterm infants and their role as a predictor of respiratory outcomes have not been studied. We hypothesized that GDF15 levels would increase with gestational age at birth, and that postnatal GDF15 will be correlated with adverse respiratory outcomes in preterm infants. Scavenged blood samples were retrieved …

Resident Education And Virtual Medicine: A Faculty Development Session To Enhance Trainee Skills In The Realm Of Telemedicine, Anna E Rueda, Ana C Monterrey, Margaret Wood, Linessa Zuniga, Betty Del Rio Rodriguez

Faculty, Staff and Students Publications

INTRODUCTION: COVID-19 accelerated the use of telemedicine. Subsequently, clinical sites began conducting virtual visits. Academic institutions implemented telemedicine for patient care and simultaneously had to teach residents the logistics and best practices. To meet this need, we developed a training session for faculty focused on telemedicine best practices and teaching telemedicine in the pediatric realm.

METHODS: We designed this training session based on institutional and society guidelines and faculty experience with telemedicine. Objectives included telemedicine documentation, triage, counseling, and ethical issues in telemedicine. We conducted all sessions in a 60-minute or 90-minute format over a virtual platform for small and …

Lox Upregulates Fak Phosphorylation To Promote Metastasis In Osteosarcoma, Xiang Chen, Margaret Clement, M John Hicks, Poonam Sarkar, M Waleed Gaber, Tsz-Kwong Man

Faculty, Staff and Students Publications

Osteosarcoma is a malignant bone tumor that commonly occurs in the pediatric population. Despite the use of chemotherapy and surgery, metastasis remains to be the leading cause of death in patients with osteosarcoma. We have previously reported that cytoplasmic mislocalization of p27 is associated with a poor outcome in osteosarcoma. In this study, we further show that lysyl oxidase (LOX) expression was associated with p27 mislocalization. LOX is an enigmatic molecule that acts as a tumor suppressor or a metastatic promoter; however, its role in osteosarcoma is still unclear. Hence, we performed both

Proximity-Dependent Biotin Labeling In Testicular Germ Cells Identified Tesmin-Associated Proteins, Seiya Oura, Akinori Ninomiya, Fuminori Sugihara, Martin M Matzuk, Masahito Ikawa

Faculty, Staff and Students Publications

Characterization of protein-protein interactions (PPI) is a key to understanding the functions of proteins of interest. Recently developed proximity-dependent biotin identification (BioID) has been actively investigated as an alternative PPI mapping method because of its usefulness in uncovering transient PPI. Here, as an example of proximity labeling proteomics application in the testis, we generated two transgenic mouse lines expressing two biotin ligases (BioID2 or TurboID) fused with TESMIN, which translocates from the cytosol to the nucleus during meiotic progression and is required for reproduction. The BioID2 transgene, albeit not the TurboID transgene, rescued fertility defects of the Tesmin KO male …

Single Cell Rna Sequencing Of The Adult Drosophila Eye Reveals Distinct Clusters And Novel Marker Genes For All Major Cell Types, Kelvin Yeung, Komal Kumar Bollepogu Raja, Yoon-Kyung Shim, Yumei Li, Rui Chen, Graeme Mardon

Faculty, Staff and Students Publications

The adult Drosophila eye is a powerful model system for phototransduction and neurodegeneration research. However, single cell resolution transcriptomic data are lacking for this tissue. We present single cell RNA-seq data on 1-day male and female, 3-day and 7-day old male adult eyes, covering early to mature adult eyes. All major cell types, including photoreceptors, cone and pigment cells in the adult eye were captured and identified. Our data sets identified novel cell type specific marker genes, some of which were validated in vivo. R7 and R8 photoreceptors form clusters that reflect their specific Rhodopsin expression and the specific Rhodopsin …

Clinical And Molecular Insights Into Gastrointestinal Dysfunction In Myotonic Dystrophy Types 1 & 2, Janel A M Peterson, Thomas A Cooper

Faculty, Staff and Students Publications

Myotonic dystrophy (DM) is a highly variable, multisystemic disorder that clinically affects one in 8000 individuals. While research has predominantly focused on the symptoms and pathological mechanisms affecting striated muscle and brain, DM patient surveys have identified a high prevalence for gastrointestinal (GI) symptoms amongst affected individuals. Clinical studies have identified chronic and progressive dysfunction of the esophagus, stomach, liver and gallbladder, small and large intestine, and rectum and anal sphincters. Despite the high incidence of GI dysmotility in DM, little is known regarding the pathological mechanisms leading to GI dysfunction. In this review, we summarize results from clinical and …

Depletion Of Cd206+ M2-Like Macrophages Induces Fibro-Adipogenic Progenitors Activation And Muscle Regeneration, Allah Nawaz, Muhammad Bilal, Shiho Fujisaka, Tomonobu Kado, Muhammad Rahil Aslam, Saeed Ahmed, Keisuke Okabe, Yoshiko Igarashi, Yoshiyuki Watanabe, Takahide Kuwano, Koichi Tsuneyama, Ayumi Nishimura, Yasuhiro Nishida, Seiji Yamamoto, Masakiyo Sasahara, Johji Imura, Hisashi Mori, Martin M Matzuk, Fujimi Kudo, Ichiro Manabe, Akiyoshi Uezumi, Takashi Nakagawa, Yumiko Oishi, Kazuyuki Tobe

Faculty, Staff and Students Publications

Muscle regeneration requires the coordination of muscle stem cells, mesenchymal fibro-adipogenic progenitors (FAPs), and macrophages. How macrophages regulate the paracrine secretion of FAPs during the recovery process remains elusive. Herein, we systemically investigated the communication between CD206+ M2-like macrophages and FAPs during the recovery process using a transgenic mouse model. Depletion of CD206+ M2-like macrophages or deletion of CD206+ M2-like macrophages-specific TGF-β1 gene induces myogenesis and muscle regeneration. We show that depletion of CD206+ M2-like macrophages activates FAPs and activated FAPs secrete follistatin, a promyogenic factor, thereby boosting the recovery process. Conversely, deletion of the FAP-specific follistatin gene results in …

Clinical And Molecular Features Of Pediatric Cancer Patients With Lynch Syndrome, Sarah Scollon, Mohammad K Eldomery, Jacquelyn Reuther, Frank Y Lin, Samara L Potter, Lauren Desrosiers, Kenneth L Mcclain, Valeria Smith, Jack Meng-Fen Su, Rajkumar Venkatramani, Jianhong Hu, Viktoriya Korchina, Neda Zarrin-Khameh, Richard A Gibbs, Donna M Muzny, Christine Eng, Angshumoy Roy, D Williams Parsons, Sharon E Plon

Faculty, Staff and Students Publications

BACKGROUND: The association of childhood cancer with Lynch syndrome is not established compared with the significant pediatric cancer risk in recessive constitutional mismatch repair deficiency syndrome (CMMRD).

PROCEDURE: We describe the clinical features, germline analysis, and tumor genomic profiling of patients with Lynch syndrome among patients enrolled in pediatric cancer genomic studies.

RESULTS: There were six of 773 (0.8%) pediatric patients with solid tumors identified with Lynch syndrome, defined as a germline heterozygous pathogenic variant in one of the mismatch repair (MMR) genes (three with MSH6, two with MLH1, and one with MSH2). Tumor analysis demonstrated evidence for somatic second …

Validation Of Atovaquone Plasma Levels By Liquid Chromatography-Tandem Mass Spectrometry For Therapeutic Drug Monitoring In Pediatric Patients, Thomas D Horvath, Izmarie Poventud-Fuentes, Lily Olayinka, Asha James, Sigmund J Haidacher, Kathleen M Hoch, Alexandra M Stevens, Anthony M Haag, Sridevi Devaraj

Faculty, Staff and Students Publications

BACKGROUND: Atovaquone has traditionally been used as an antiparasitic and antifungal agent, but recent studies have shown its potential as an anticancer agent. The high variability in atovaquone bioavailability highlights the need for therapeutic drug monitoring, especially in pediatric patients. The goal of our study was to develop and validate the performance of an assay to quantify atovaquone plasma concentrations collected from pediatric cancer patients using LC-MS/MS.

METHODS: Atovaquone was extracted from a 10 µL volume of K

RESULTS: Atovaquone and its deuterated internal standard were analyzed using a gradient chromatographic method that had an overall cycle-time of 7.4 min …