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Labrad : Vol 45, Issue 1 - February 2019, Aga Khan University Hospital, Karachi 2019 Aga Khan University

Labrad : Vol 45, Issue 1 - February 2019, Aga Khan University Hospital, Karachi

LABRAD

  • Cardiac Manifestation of Inherited Metabolic Disorders
  • Utility of Plasma Homocysteine in Identifying Inherited Metabolic Disorders (IMDs)
  • Chediak-Higashi Syndrome, an Inherited Disorder in Phagocytic Function
  • Radiology-Pathology Correlation Rare Diseases of Bone
  • Dried Blood Spot (DBS) Sampling: A Method for Blood Collection without Venipuncture
  • Newborn Screening Program for Congenital Hypothyroidism
  • Rare Disease in Dermatopathology
  • Screening for Carbohydrate Metabolism Disorders by Sugar Chromatography in Urine
  • Hypophosphatasia a Rare Skeletal Disorder


Model-Based Virtual Patient Analysis Of Human Liver Regeneration Predicts Critical Perioperative Factors Controlling The Dynamic Mode Of Response To Resection., Babita Verma, Pushpavanam Subramaniam, Rajanikanth Vadigepalli 2019 Thomas Jefferson University; Indian Institute of Technology-Madras, Chennai

Model-Based Virtual Patient Analysis Of Human Liver Regeneration Predicts Critical Perioperative Factors Controlling The Dynamic Mode Of Response To Resection., Babita Verma, Pushpavanam Subramaniam, Rajanikanth Vadigepalli

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: Liver has the unique ability to regenerate following injury, with a wide range of variability of the regenerative response across individuals. Existing computational models of the liver regeneration are largely tuned based on rodent data and hence it is not clear how well these models capture the dynamics of human liver regeneration. Recent availability of human liver volumetry time series data has enabled new opportunities to tune the computational models for human-relevant time scales, and to predict factors that can significantly alter the dynamics of liver regeneration following a resection.

METHODS: We utilized a mathematical model that integrates signaling ...


Urease Is An Essential Component Of The Acid Response Network Of Staphylococcus Aureus And Is Required For A Persistent Murine Kidney Infection, Chunyi Zhou, Fatema Bhinderwala, McKenzie K. Lehman, Vinai Chittezham Thomas, Sujata S. Chaudhari, Kelsey J. Yamada, Kirk W. Foster, Robert Powers, Tammy Kielian, Paul D. Fey 2019 University of Nebraska Medical Center

Urease Is An Essential Component Of The Acid Response Network Of Staphylococcus Aureus And Is Required For A Persistent Murine Kidney Infection, Chunyi Zhou, Fatema Bhinderwala, Mckenzie K. Lehman, Vinai Chittezham Thomas, Sujata S. Chaudhari, Kelsey J. Yamada, Kirk W. Foster, Robert Powers, Tammy Kielian, Paul D. Fey

Journal Articles: Pathology and Microbiology

Staphylococcus aureus causes acute and chronic infections resulting in significant morbidity. Urease, an enzyme that generates NH3 and CO2 from urea, is key to pH homeostasis in bacterial pathogens under acidic stress and nitrogen limitation. However, the function of urease in S. aureus niche colonization and nitrogen metabolism has not been extensively studied. We discovered that urease is essential for pH homeostasis and viability in urea-rich environments under weak acid stress. The regulation of urease transcription by CcpA, Agr, and CodY was identified in this study, implying a complex network that controls urease expression in response to changes in metabolic ...


Analytical Validation Of A Prognostic Prostate Cancer Gene Expression Assay Using Formalin Fixed Paraffin Embedded Tissue., Paul W. Medlow, Christopher J. Steele, Andrena M. McCavigan, Wesley Reardon, Christopher M. Brown, Shauna M. Lambe, Felipe AA Ishiy, Steven M. Walker, Gemma E. Logan, Olaide Y. Raji, Viktor Berge, Betina Katz, Elaine W. Kay, Katherine M. Sheehan, Ronald W. Watson, Denis P. Harkin, Richard D. Kennedy, Laura A. Knight 2018 Almac Diagnostics Ltd.

Analytical Validation Of A Prognostic Prostate Cancer Gene Expression Assay Using Formalin Fixed Paraffin Embedded Tissue., Paul W. Medlow, Christopher J. Steele, Andrena M. Mccavigan, Wesley Reardon, Christopher M. Brown, Shauna M. Lambe, Felipe Aa Ishiy, Steven M. Walker, Gemma E. Logan, Olaide Y. Raji, Viktor Berge, Betina Katz, Elaine W. Kay, Katherine M. Sheehan, Ronald W. Watson, Denis P. Harkin, Richard D. Kennedy, Laura A. Knight

Pathology Articles

BACKGROUND: There is a clear need for assays that can predict the risk of metastatic prostate cancer following curative procedures. Importantly these assays must be analytically robust in order to provide quality data for important clinical decisions. DNA microarray based gene expression assays measure several analytes simultaneously and can present specific challenges to analytical validation. This study describes the analytical validation of one such assay designed to predict metastatic recurrence in prostate cancer using primary formalin fixed paraffin embedded tumour material.

METHODS: Accuracy was evaluated with a method comparison study between the assay development platform (Prostate Disease Specific Array) and ...


Loss-Of-Function Mutations In Atp6ap1 And Atp6ap2 In Granular Cell Tumors., Fresia Pareja, Alissa H. Brandes, Thais Basili, Pier Selenica, Felipe C. Geyer, Dan Fan, Arnaud Da Cruz Paula, Rahul Kumar, David N. Brown, Rodrigo Gularte-Mérida, Barbara Alemar, Rui Bi, Raymond S. Lim, Ino de Bruijn, Sho Fujisawa, Rui Gardner, Elvin Feng, Anqi Li, Edaise M. da Silva, John R. Lozada, Pedro Blecua, Leona Cohen-Gould, Achim A. Jungbluth, Emad A. Rakha, Ian O. Ellis, Maria I.A. Edelweiss, Juan P. Palazzo, Larry Norton, Travis Hollmann, Marcia Edelweiss, Brian P. Rubin, Britta Weigelt, Jorge S. Reis-Filho 2018 Memorial Sloan Kettering Cancer Center

Loss-Of-Function Mutations In Atp6ap1 And Atp6ap2 In Granular Cell Tumors., Fresia Pareja, Alissa H. Brandes, Thais Basili, Pier Selenica, Felipe C. Geyer, Dan Fan, Arnaud Da Cruz Paula, Rahul Kumar, David N. Brown, Rodrigo Gularte-Mérida, Barbara Alemar, Rui Bi, Raymond S. Lim, Ino De Bruijn, Sho Fujisawa, Rui Gardner, Elvin Feng, Anqi Li, Edaise M. Da Silva, John R. Lozada, Pedro Blecua, Leona Cohen-Gould, Achim A. Jungbluth, Emad A. Rakha, Ian O. Ellis, Maria I.A. Edelweiss, Juan P. Palazzo, Larry Norton, Travis Hollmann, Marcia Edelweiss, Brian P. Rubin, Britta Weigelt, Jorge S. Reis-Filho

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Granular cell tumors (GCTs) are rare tumors that can arise in multiple anatomical locations, and are characterized by abundant intracytoplasmic granules. The genetic drivers of GCTs are currently unknown. Here, we apply whole-exome sequencing and targeted sequencing analysis to reveal mutually exclusive, clonal, inactivating somatic mutations in the endosomal pH regulators ATP6AP1 or ATP6AP2 in 72% of GCTs. Silencing of these genes in vitro results in impaired vesicle acidification, redistribution of endosomal compartments, and accumulation of intracytoplasmic granules, recapitulating the cardinal phenotypic characteristics of GCTs and providing a novel genotypic-phenotypic correlation. In addition, depletion of ATP6AP1 or ATP6AP2 results in ...


Bilateral Serous Tubal Intraepithelial Carcinoma Associated With High-Grade Serous Carcinoma Of The Peritoneum: Evidence For Transcoelomic Tumor Spread By Extended Lymph Node Evaluation, Hermann Brustmann 2018 Department of Pathology, Landesklinikum Baden-Moedling, Austria

Bilateral Serous Tubal Intraepithelial Carcinoma Associated With High-Grade Serous Carcinoma Of The Peritoneum: Evidence For Transcoelomic Tumor Spread By Extended Lymph Node Evaluation, Hermann Brustmann

POG In Press

Serous tubal intraepithelial carcinoma (STIC) is now considered a putative precursor lesion of most extrauterine high-grade serous carcinomas (HGSC). It is frequently reported in high-risk women and women with advanced-stage serous carcinoma. This case study reports a serous high-grade carcinoma (HGSC) consisting of a bilateral STIC with a focus of stromal invasion in the left tube, and a peritoneal HGSC. The grossly normal-appearing tubes including the fimbriated ends were sectioned following the SEE-FIM protocol. In both tubes, tumor aggregates were exfoliated extensively to the tubal lumens. The neoplastic epithelia in any location were diffusely positive for p53 in strong nuclear ...


Task Sharing And Shifting To Provide Pathology Diagnostic Services: The Kenya Fine-Needle Aspiration Biopsy Cytology And Bone Marrow Aspiration And Trephine Biopsy Training Program, Shahin Sayed, Andrew Field, Jamilla Rajab, Anderson Mutuiri, Jessie Githanga, Mary Mungania, Nancy Okinda, Zahir Moloo, Abubakar Abdillah, Brian Ayara, Erick Chesori, Julia Muthua, Leah Obosy, Thaddeus Massawa, Okoth Obiero, Elizabeth Kagotho, Peter K. Shikuku, Andrew K. Gachii, Eunidah Migide, Donstefano Muninzwa, Sanford M. Dawsey, Lucy Muchiri 2018 Aga Khan University

Task Sharing And Shifting To Provide Pathology Diagnostic Services: The Kenya Fine-Needle Aspiration Biopsy Cytology And Bone Marrow Aspiration And Trephine Biopsy Training Program, Shahin Sayed, Andrew Field, Jamilla Rajab, Anderson Mutuiri, Jessie Githanga, Mary Mungania, Nancy Okinda, Zahir Moloo, Abubakar Abdillah, Brian Ayara, Erick Chesori, Julia Muthua, Leah Obosy, Thaddeus Massawa, Okoth Obiero, Elizabeth Kagotho, Peter K. Shikuku, Andrew K. Gachii, Eunidah Migide, Donstefano Muninzwa, Sanford M. Dawsey, Lucy Muchiri

Pathology, East Africa

Purpose: Fine-needle aspiration biopsy (FNAB) cytology is a simple, inexpensive, and accurate diagnostic test for benign, infectious, and malignant lesions of the breast, thyroid, lymph nodes, and other organs. Similarly, bone marrow aspiration and trephine (BMAT) biopsy procedures are relatively simple and inexpensive techniques that are important for diagnosing and monitoring many hematologic diseases including leukemias and lymphomas. However, the scarcity of pathologists in Kenya limits patient access to these simple diagnostic tests. We describe a task sharing and shifting program that sought to improve the provision of FNABs and BMAT biopsies in tertiary public hospitals in Kenya.

Methods: Between ...


Labrad : Vol 44, Issue 3 - December 2018, Aga Khan University Hospital, Karachi 2018 Aga Khan University

Labrad : Vol 44, Issue 3 - December 2018, Aga Khan University Hospital, Karachi

LABRAD

  • CD20 Negative B-Cell Lymphomas
  • Quantification of Monoclonal Protein
  • A Quick Guide to Immunofixation Electrophoresis
  • Autologous Bone Marrow Transplantation at AKU
  • Judicious Use of Immunohistochemistry & Ancillary Techniques in Precise Categorization of Lymphoproliferative Disorders


Seven Decades Of Vitamin D Research In Pakistan : Too Little, Too Much Or Just Right!, Aysha Habib Khan 2018 Aga Khan University

Seven Decades Of Vitamin D Research In Pakistan : Too Little, Too Much Or Just Right!, Aysha Habib Khan

Department of Pathology and Laboratory Medicine

No abstract provided.


Mutant Ubqln2p497h In Motor Neurons Leads To Als-Like Phenotypes And Defective Autophagy In Rats, Tianhong Chen, Bo Huang, Xinglong Shi, Limo Gao, Cao Huang 2018 Thomas Jefferson University

Mutant Ubqln2p497h In Motor Neurons Leads To Als-Like Phenotypes And Defective Autophagy In Rats, Tianhong Chen, Bo Huang, Xinglong Shi, Limo Gao, Cao Huang

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Mutations in ubiquilin2 (UBQLN2) have been linked to abnormal protein aggregation in amyotrophic lateral sclerosis (ALS). The mechanisms underlying UBQLN2-related neurodegenerative diseases remain unclear. Using a tetracycline-regulated gene expression system, the ALS-linked UBQLN2P497H mutant was selectively expressed in either the spinal motor neurons or astrocytes in rats. We found that selectively expressing mutant UBQLN2P497H in the spinal motor neurons caused several core features of ALS, including the progressive degeneration of motor neurons, the denervation atrophy of skeletal muscles, and the abnormal protein accumulation. Furthermore, mutant UBQLN2P497H accumulation was associated with an age-dependent decrease in several core autophagy-related proteins. ALS-like phenotypes ...


Serous Cystadenoma Of Pancreas : A Clinicopathologic Experience Of 23 Cases From A Major Tertiary Care Center, Muhammad Usman Tariq, Zubair Ahmad, Jamshid Abdul Ghafar, Nasir Ud Din 2018 Aga Khan University

Serous Cystadenoma Of Pancreas : A Clinicopathologic Experience Of 23 Cases From A Major Tertiary Care Center, Muhammad Usman Tariq, Zubair Ahmad, Jamshid Abdul Ghafar, Nasir Ud Din

Department of Pathology and Laboratory Medicine

Background: Serous cystadenomas of pancreas are rare benign epithelial neoplasms, which predominantly occur in the pancreatic body and tail of elderly females. Majority of these tumors have microcystic appearance. Macrocystic and solid variants have also been described. A number of more aggressive cystic pancreatic lesions are included in the differential diagnosis. Distinction from such lesions is important for optimal management.
Objective: Our aim was to study the clinical and histological features of serous cystadenomas which would be helpful in making their correct diagnosis and understanding their behavior.
Methods: We reviewed 23 cases of serous cystadenomas diagnosed in our institution between ...


Hypoxia-Mediated Mitochondria Apoptosis Inhibition Induces Temozolomide Treatment Resistance Through Mir-26a/Bad/Bax Axis., Xin Ge, Min-Hong Pan, Lin Wang, Wei Li, Chengfei Jiang, Jun He, Khaled Abouzid, Ling-Zhi Liu, Zhumei Shi, Bing-Hua Jiang 2018 Nanjing Medical University; The University of Iowa

Hypoxia-Mediated Mitochondria Apoptosis Inhibition Induces Temozolomide Treatment Resistance Through Mir-26a/Bad/Bax Axis., Xin Ge, Min-Hong Pan, Lin Wang, Wei Li, Chengfei Jiang, Jun He, Khaled Abouzid, Ling-Zhi Liu, Zhumei Shi, Bing-Hua Jiang

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Glioblastoma multiforme (GBM) is one of the most hypoxic tumors of the central nervous system. Although temozolomide (TMZ) is an effective clinical agent in the GBM therapy, the hypoxic microenvironment remains a major barrier in glioma chemotherapy resistance, and the underlying mechanisms are poorly understood. Here, we find hypoxia can induce the protective response to mitochondrion via HIF-1α-mediated miR-26a upregulation which is associated with TMZ resistance in vitro and in vivo. Further, we demonstrated that HIF-1α/miR-26a axis strengthened the acquisition of TMZ resistance through prevention of Bax and Bad in mitochondria dysfunction in GBM. In addition, miR-26a expression levels ...


Potential Role Of Csf Cytokine Profiles In Discriminating Infectious From Non-Infectious Cns Disorders., Danielle Fortuna, D. Craig Hooper, Amity L. Roberts, Larry A. Harshyne, Michelle Nagurney, Mark T. curtis 2018 Hospital of the University of Pennsylvania

Potential Role Of Csf Cytokine Profiles In Discriminating Infectious From Non-Infectious Cns Disorders., Danielle Fortuna, D. Craig Hooper, Amity L. Roberts, Larry A. Harshyne, Michelle Nagurney, Mark T. Curtis

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Current laboratory testing of cerebrospinal fluid (CSF) does not consistently discriminate between different central nervous system (CNS) disease states. Rapidly distinguishing CNS infections from other brain and spinal cord disorders that share a similar clinical presentation is critical. New approaches focusing on aspects of disease biology, such as immune response profiles that can have stimulus-specific attributes, may be helpful. We undertook this preliminary proof-of-concept study using multiplex ELISA to measure CSF cytokine levels in various CNS disorders (infections, autoimmune/demyelinating diseases, lymphomas, and gliomas) to determine the potential utility of cytokine patterns in differentiating CNS infections from other CNS diseases ...


Bacterial Contamination Of Platelets For Transfusion: Strategies For Prevention., Jerrold H. Levy, Matthew D. Neal, Jay H. Herman 2018 Duke University Hospital

Bacterial Contamination Of Platelets For Transfusion: Strategies For Prevention., Jerrold H. Levy, Matthew D. Neal, Jay H. Herman

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Platelet transfusions carry greater risks of infection, sepsis, and death than any other blood product, owing primarily to bacterial contamination. Many patients may be at particular risk, including critically ill patients in the intensive care unit. This narrative review provides an overview of the problem and an update on strategies for the prevention, detection, and reduction/inactivation of bacterial contaminants in platelets. Bacterial contamination and septic transfusion reactions are major sources of morbidity and mortality. Between 1:1000 and 1:2500 platelet units are bacterially contaminated. The skin bacterial microflora is a primary source of contamination, and enteric contaminants are ...


Multiple Tumor Suppressors Regulate A Hif-Dependent Negative Feedback Loop Via Isgf3 In Human Clear Cell Renal Cancer., Lili Liao, Zongzhi Z. Liu, Lauren Langbein, Weijia Cai, Eun-Ah Cho, Jie Na, Xiaohua Niu, Wei Jiang, Zhijiu Zhong, Wesley L. Cai, Geetha Jagannathan, Essel Dulaimi, Joseph R. Testa, Robert G. Uzzo, Yuxin Wang, George R. Stark, Jianxin Sun, Stephen C. Peiper, Yaomin Xu, Qin Yan, Haifeng Yang 2018 Thomas Jefferson University; Yale University

Multiple Tumor Suppressors Regulate A Hif-Dependent Negative Feedback Loop Via Isgf3 In Human Clear Cell Renal Cancer., Lili Liao, Zongzhi Z. Liu, Lauren Langbein, Weijia Cai, Eun-Ah Cho, Jie Na, Xiaohua Niu, Wei Jiang, Zhijiu Zhong, Wesley L. Cai, Geetha Jagannathan, Essel Dulaimi, Joseph R. Testa, Robert G. Uzzo, Yuxin Wang, George R. Stark, Jianxin Sun, Stephen C. Peiper, Yaomin Xu, Qin Yan, Haifeng Yang

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Whereas VHL inactivation is a primary event in clear cell renal cell carcinoma (ccRCC), the precise mechanism(s) of how this interacts with the secondary mutations in tumor suppressor genes, including PBRM1, KDM5C/JARID1C, SETD2, and/or BAP1, remains unclear. Gene expression analyses reveal that VHL, PBRM1, or KDM5C share a common regulation of interferon response expression signature. Loss of HIF2α, PBRM1, or KDM5C in VHL-/-cells reduces the expression of interferon stimulated gene factor 3 (ISGF3), a transcription factor that regulates the interferon signature. Moreover, loss of SETD2 or BAP1 also reduces the ISGF3 level. Finally, ISGF3 is strongly ...


Effect Of Positive Patient Identification On Wrong Blood In Tube Errors: A Single Center Experience, Faisal Huq Ronny, MD, PhD, Mary Harach, BS, MT(ASCP), CQA(ASQ), SSGB, Jay H. Herman, MD, FCAP 2018 Thomas Jefferson University

Effect Of Positive Patient Identification On Wrong Blood In Tube Errors: A Single Center Experience, Faisal Huq Ronny, Md, Phd, Mary Harach, Bs, Mt(Ascp), Cqa(Asq), Ssgb, Jay H. Herman, Md, Fcap

Department of Pathology, Anatomy, and Cell Biology Posters

No abstract provided.


Expression Analysis Of Cyclooxygenase-2 In Patients Suffering From Esophageal Squamous Cell Carcinoma, Shahida Tasneem, , Muhammad Tahir Sarwa, Muhammad Rizwan Bashi, Hamid Hussain, Jawad Ahmed, Shahid Pervez 2018 Khyber Medical University

Expression Analysis Of Cyclooxygenase-2 In Patients Suffering From Esophageal Squamous Cell Carcinoma, Shahida Tasneem, , Muhammad Tahir Sarwa, Muhammad Rizwan Bashi, Hamid Hussain, Jawad Ahmed, Shahid Pervez

Department of Pathology and Laboratory Medicine

Esophageal squamous cell carcinoma (ESCC) is one of the aggressive malignancies and mechanisms underlying its pathogenesis remain unclear. Cyclooxygenase-2 (COX-2) enzyme system plays a crucial role in many gastrointestinal malignancies and is an important regulator of cell growth, proliferation, apoptosis, differentiation and transformation. More precise outcome of COX-2 in ESCC is less investigated. In this study we investigated the risk factors of ESCC and expression of COX-2 in Carcinoma in situ (CIS) and ESCC compared to normal esophageal mucosa. ESCC relationship to clinico-pathological parameters using immunohistochemistry was also part of this investigation. Current study was conducted in the Institute of ...


Metformin Clinical Trial In Hpv+ And Hpv- Head And Neck Squamous Cell Carcinoma: Impact On Cancer Cell Apoptosis And Immune Infiltrate., Joseph M. Curry, Jennifer Johnson, Mehri Mollaee, Patrick Tassone, Dev Amin, Alexander Knops, Diana Whitaker Menezes, My Mahoney, Andrew P. South, Ulrich Rodeck, Tingting Zhan, Larry A. Harshyne, Nancy Philp, Adam J. Luginbuhl, David Cognetti, Madalina Tuluc, Ubaldo E. Martinez-Outshoorn, MD 2018 Thomas Jefferson University

Metformin Clinical Trial In Hpv+ And Hpv- Head And Neck Squamous Cell Carcinoma: Impact On Cancer Cell Apoptosis And Immune Infiltrate., Joseph M. Curry, Jennifer Johnson, Mehri Mollaee, Patrick Tassone, Dev Amin, Alexander Knops, Diana Whitaker Menezes, My Mahoney, Andrew P. South, Ulrich Rodeck, Tingting Zhan, Larry A. Harshyne, Nancy Philp, Adam J. Luginbuhl, David Cognetti, Madalina Tuluc, Ubaldo E. Martinez-Outshoorn, Md

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

Background: Metformin, an oral anti-hyperglycemic drug which inhibits mitochondrial complex I and oxidative phosphorylation has been reported to correlate with improved outcomes in head and neck squamous cell carcinoma (HNSCC) and other cancers. This effect is postulated to occur through disruption of tumor-driven metabolic and immune dysregulation in the tumor microenvironment (TME). We report new findings on the impact of metformin on the tumor and immune elements of the TME from a clinical trial of metformin in HNSCC. Methods: Human papilloma virus-(HPV-) tobacco+ mucosal HNSCC samples (n = 12) were compared to HPV+ oropharyngeal squamous cell carcinoma (OPSCC) samples (n ...


Mitochondrial Fusion And Bid-Mediated Mitochondrial Apoptosis Are Perturbed By Alcohol With Distinct Dependence On Its Metabolism, Shamim Naghdi, William S. Slovinsky, Muniswamy Madesh, Emanual Rubin, György Hajnóczky 2018 Thomas Jefferson University

Mitochondrial Fusion And Bid-Mediated Mitochondrial Apoptosis Are Perturbed By Alcohol With Distinct Dependence On Its Metabolism, Shamim Naghdi, William S. Slovinsky, Muniswamy Madesh, Emanual Rubin, György Hajnóczky

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Environmental stressors like ethanol (EtOH) commonly target mitochondria to influence the cell’s fate. Recent literature supports that chronic EtOH exposure suppresses mitochondrial dynamics, central to quality control, and sensitizes mitochondrial permeability transition pore opening to promote cell death. EtOH-induced tissue injury is primarily attributed to its toxic metabolic products but alcoholism also impairs tissues that poorly metabolize EtOH. We embarked on studies to determine the respective roles of EtOH and its metabolites in mitochondrial fusion and tBid-induced mitochondrial apoptosis. We used HepG2 cells that do not metabolize EtOH and its engineered clone that expresses EtOH-metabolizing Cytochrome P450 E2 and ...


Microtubule-Associated Protein 1 Light Chain 3b, (Lc3b) Is Necessary To Maintain Lipid-Mediated Homeostasis In The Retinal Pigment Epithelium., Anuradha Dhingra, Brent A Bell, Neal S. Peachey, Lauren L. Daniele, Juan Reyes-Reveles, Rachel C. Sharp, Bokkyoo Jun, Nicolas G. Bazan, Janet R. Sparrow, Hye Jin Kim, Nancy J. Philp, Kathleen Boesze-Battaglia 2018 University of Pennsylvania

Microtubule-Associated Protein 1 Light Chain 3b, (Lc3b) Is Necessary To Maintain Lipid-Mediated Homeostasis In The Retinal Pigment Epithelium., Anuradha Dhingra, Brent A Bell, Neal S. Peachey, Lauren L. Daniele, Juan Reyes-Reveles, Rachel C. Sharp, Bokkyoo Jun, Nicolas G. Bazan, Janet R. Sparrow, Hye Jin Kim, Nancy J. Philp, Kathleen Boesze-Battaglia

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Like other neurons, retinal cells utilize autophagic pathways to maintain cell homeostasis. The mammalian retina relies on heterophagy and selective autophagy to efficiently degrade and metabolize ingested lipids with disruption in autophagy associated degradation contributing to age related retinal disorders. The retinal pigment epithelium (RPE) supports photoreceptor cell renewal by daily phagocytosis of shed photoreceptor outer segments (OS). The daily ingestion of these lipid-rich OS imposes a constant degradative burden on these terminally differentiated cells. These cells rely on Microtubule-Associated Protein 1 Light Chain 3 (LC3) family of proteins for phagocytic clearance of the ingested OS. The LC3 family comprises ...


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