Pathology Commons^™

Mdivi-1, A Mitochondrial Fission Inhibitor, Modulates T Helper Cells And Suppresses The Development Of Experimental Autoimmune Encephalomyelitis., Yan-Hua Li, Fang Xu, Rodolfo Thome, Min-Fang Guo, Man-Luan Sun, Guo-Bin Song, Rui-Lan Li, Zhi Chai, Bogoljub Ciric, A. M. Rostami, Mark T. Curtis, Cun-Gen Ma, Guang-Xian Zhang

Department of Neurology Faculty Papers

BACKGROUND: Unrestrained activation of Th1 and Th17 cells is associated with the pathogenesis of multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE). While inactivation of dynamin-related protein 1 (Drp1), a GTPase that regulates mitochondrial fission, can reduce EAE severity by protecting myelin from demyelination, its effect on immune responses in EAE has not yet been studied.

METHODS: We investigated the effect of Mdivi-1, a small molecule inhibitor of Drp1, on EAE. Clinical scores, inflammation, demyelination and Drp1 activation in the central nervous system (CNS), and T cell responses in both CNS and periphery were determined.

RESULTS: Mdivi-1 effectively …

Spg7 Targets The M-Aaa Protease Complex To Process Mcu For Uniporter Assembly, Ca2 Influx, And Regulation Of Mitochondrial Permeability Transition Pore Opening, Stephen Hurst, Ariele Baggett, György Csordás, Shey-Shing Sheu

Center for Translational Medicine Faculty Papers

The mitochondrial matrix ATPase associated with diverse cellular activities (m-AAA) protease spastic paraplegia 7 (SPG7) has been recently implicated as either a negative or positive regulatory component of the mitochondrial permeability transition pore (mPTP) by two research groups. To address this controversy, we investigated possible mechanisms that explain the discrepancies between these two studies. We found that loss of the SPG7 gene increased resistance to Ca²-induced mPTP opening. However, this occurs independently of cyclophilin D (cyclosporine A insensitive) rather it is through decreased mitochondrial Ca² concentrations and subsequent adaptations mediated by impaired formation of functional mitochondrial Ca …

Antibiotic Resistance And Molecular Characterization Of Bacteremia Escherichia Coli Isolates From Newborns In The United States., Bryan K. Cole, Marko Ilikj, Cindy B. Mccloskey, Susana Chavez-Bueno

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Escherichia coli is a major cause of neonatal sepsis. Contemporary antibiotic resistance data and molecular characterization of neonatal E. coli bacteremia isolates in the US are limited.

METHODS: E. coli blood isolates, antibiotic susceptibility data, and clinical characteristics were obtained from prospectively identified newborns from 2006 to 2016. The E. coli isolates were classified using an updated phylogrouping method and multi-locus sequence typing. The presence of several virulence traits was also determined.

RESULTS: Forty-three newborns with E. coli bacteremia were identified. Mean gestational age was 32.3 (SD±5.4) weeks. Median age was 7 days (interquartile range 0-10). Mortality (28%) occurred …

Metastatic Breast Cancer In Kenya: Presentation, Pathologic Characteristics, And Patterns-Findings From A Tertiary Cancer Center, Etoroabasi Ekpe, Asim Jamal, Jasmit Shah, Judith S. Jacobson, Shahin Sayed

Internal Medicine, East Africa

Purpose: The purpose of this research was to describe the sociodemographic and clinical characteristics of Kenyan women with metastatic breast cancer diagnosed and treated at Aga Khan University Hospital in Nairobi, Kenya from 2012 to 2018.

Patients and Methods: We reviewed charts of Kenyan women with metastatic breast cancer and analyzed sociodemographic data, breast cancer risk factors, and tumor characteristics associated with stage at diagnosis, receptor status (ie, estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 [HER2]), and site of metastasis using χ2, analysis of variance, two-sample t tests, and logistic regressions.

Results: A total of 125 …

Acinetobacter Infections: A Retrospective Study To Determine In Hospital Mortality Rate And Clinical Factors Associated With Mortality, Rajiv Patel, Jasmit Shah, Gunturu Revathi, Wangari Siika, Reena Shah

Internal Medicine, East Africa

A retrospective case series of acinetobacter infections at a tertiary hospital in Nairobi was conducted to determine the mortality rate and factors associated with mortality. Over an eight-year period, 80 clinically significant infections were identified. The majority of infections were ventilator-associated pneumonia (40%) and bloodstream infections (30%). Eighty-six percent of the isolates were multi-drug resistant. The mortality rate in the study cohort was 45%. Twelve patients grew Acinetobacter spp. within 48 h of hospitalization, and three of these patients had no prior healthcare contact. The mean Sequential Organ Failure Assessment score was associated with mortality from acinetobacter infections.

Labrad : Vol 45, Issue 2 - July 2019, Aga Khan University Hospital, Karachi

LABRAD - Departments of Pathology & Laboratory Medicine and Radiology Archives

• Novel Molecular Technique for Identifying Respiratory Tract Pathogens
• Role of Serum Galactomannan (GM) Assay in Diagnosing Invasive Aspergillosis (IA)
• Factor VIII Inhibitor – A Diagnostic Approach
• PET/CT Hybrid Imaging Technology at Aga Khan University Hospital
• Diagnostic Tests for Von Willebrand Disease
• Iron Deficiency Anemia
• Sweat Testing for Diagnosis of Cystic Fibrosis
• Flow Cytometric Identification of Abnormal B-Cells
• Direct Immunofluorescence in Bullous Skin Disorders
• Radiology-Pathology Correlation; Orthopedic Pathology
• Fecal Elastase: A Marker For Exocrine Pancreatic Function
• Edward Syndrome: Rare Autosomal Aneuploidy
• Sirolimus in Renal Transplant
• Latest Trends in Clinical Laboratory Science Technology
• Radiology-Neuropathology Correlation
• Nuchal Translucency Scan
• Bio-risk Management System in …

Unique Classification Of Parathyroid Dysfunction In Patients With Transfusion Dependent Thalassemia Major Using Nomogram: A Cross Sectional Study, Hafsa Majid, Lena Jafri, Jamsheer Jehangir Talati, Sibtain Ahmed, Bushra Moiz, Aysha Habib Khan

Department of Pathology and Laboratory Medicine

Introduction: Hypoparathyroidism is a rare complication of iron overload in patients with transfusion dependent β thalassemia major (β-TM). We aim to determine the prevalence of parathyroid dysfunction in patients with β-TM.
Methods:Diagnosed cases of transfusion dependent β-TM between 5 and 17 years of age were recruited from outpatient clinics of a non-profit organization in Karachi, Pakistan. Blood and urine samples were collected in fasting to determine Ca, P, Alb, Mg, Cr 25OHD and iPTH. Patients were grouped on the basis of upper and lower levels of Ca, 25OHD and iPTH for assessing parathyroid dysfunction into primary hypoparathyroidism [low calcium …

Gangliosides: Treatment Avenues In Neurodegenerative Disease., Pierre J. Magistretti, Fred H. Geisler, Jay S. Schneider, P. Andy Li, Hubert Fiumelli, Simonetta Sipione

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Gangliosides are cell membrane components, most abundantly in the central nervous system (CNS) where they exert among others neuro-protective and -restorative functions. Clinical development of ganglioside replacement therapy for several neurodegenerative diseases was impeded by the BSE crisis in Europe during the 1990s. Nowadays, gangliosides are produced bovine-free and new pre-clinical and clinical data justify a reevaluation of their therapeutic potential in neurodegenerative diseases. Clinical experience is greatest with monosialo-tetrahexosyl-ganglioside (GM1) in the treatment of stroke. Fourteen randomized controlled trials (RCTs) in overall >2,000 patients revealed no difference in survival, but consistently superior neurological outcomes vs. placebo. GM1 was shown …

Current Laboratory Techniques Commonly Used For The Detection Of Molecular Biomarkers And Potential Technologies On The Horizon, Muhammad Shariq Shaikh, Zeeshan Ansar Ahmed

Department of Pathology and Laboratory Medicine

No abstract provided.

Phylogenetic Estimates Of Hiv-1 Gp120 Indel Rates Across The Group M Subtypes, John Palmer, Art Poon

Western Research Forum

Insertions and deletions (indels) in the HIV-1 envelope glycoprotein gp120 play a significant role in the evolution of HIV pathogenesis and transmission fitness. While substitution rates in HIV-1 are well characterized by phylogenetic models, there is a lack of quantitative measures of indel rates in HIV-1. Here we use a dated-tip phylogenetic analysis of gp120 sequences to estimate indel rates for 7 subtypes and CRFs of HIV-1 group M.

We obtained and processed 26,359 HIV-1 gp120 sequences from the Los Alamos National Laboratory HIV Sequence database. After filtering these sequences, we extracted the conserved and variable regions from the remaining …

Antimicrobial Susceptibility Against Metronidazole And Carbapenem In Clinical Anaerobic Isolates From Pakistan, Kauser Jabeen, Yusra Shafquat, Joveria Farooqi, Kiran Mehmood, Seema Irfan, Rumina Hasan, Afia Zafar

Department of Pathology and Laboratory Medicine

Background: Globally metronidazole and carbapenem resistance in anaerobic organisms is increasing necessitating continuous surveillance to guide selection of empirical treatment. In this study we have determined metronidazole resistance in anaerobes using MIC Evaluator strips (M.I.C.E strips). Carbapenem resistance was evaluated only in metronidazole resistant isolates.
Material and methods: The study was conducted at the Aga Khan University (AKU) Hospital laboratory, Karachi, Pakistan (2014–2017). Metronidazole and imipenem resistance was evaluated using M.I.C.E strips and minimum inhibitory concentrations (MICs) were interpreted using Clinical Laboratory Standards Institute (CLSI) criteria. Clinical details including demographics, prolonged hospital stay, malignancy, transplant, dialysis, diabetes, site of infection …

Extreme Peripheral Blood Plasmacytosis Mimicking Plasma Cell Leukemia As A Presenting Feature Of Angioimmunoblastic T-Cell Lymphoma (Aitl)., Kelsey Sokol, Saritha Kartan, William T. Johnson, Onder Alpdogan, Neda Nikbakht, Bradley M. Haverkos, Jerald Z. Gong, Pierluigi Porcu

Department of Medical Oncology Faculty Papers

Angioimmunoblastic T-cell lymphoma (AITL) is one of four major subtypes of nodal peripheral T cell lymphoma, characterized by its cell of origin, the follicular helper T-cell (TFH). Patients typically present with prominent constitutional (B) symptoms, generalized lymphadenopathy, hepatosplenomegaly, cytopenias, and rash. Here we present a case of a 62-year-old male with progressive cervical adenopathy, fevers and weight loss presenting with extreme polyclonal plasmacytosis and high plasma EBV viral load. While the initial presentation appeared to mimic plasma cell leukemia or severe infection, lymph node biopsy and bone marrow biopsy confirmed a diagnosis of AITL. This case highlights the heterogeneity of …

Gm1 Ganglioside Modifies Α-Synuclein Toxicity And Is Neuroprotective In A Rat Α-Synuclein Model Of Parkinson's Disease., Jay S. Schneider, Radha Aras, Courtney K. Williams, James B. Koprich, Jonathan M. Brotchie, Vikrant Singh

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

While GM1 may interact with α-synuclein in vitro to inhibit aggregation, the ability of GM1 to protect against α-synuclein toxicity in vivo has not been investigated. We used targeted adeno-associated viral vector (AAV) overexpression of human mutant α-synuclein (A53T) in the rat substantia nigra (SN) to produce degeneration of SN dopamine neurons, loss of striatal dopamine levels, and behavioral impairment. Some animals received daily GM1 ganglioside administration for 6 weeks, beginning 24 hours after AAV-A53T administration or delayed start GM1 administration for 5 weeks beginning 3 weeks after AAV-A53T administration. Both types of GM1 administration protected against loss of SN …

Solitary Brain Metastasis: A Rare Initial Presentation Of Prostate Carcinoma, Asim Hafiz, Muneeb Uddin Karim, Bilal Mazhar Qureshi, Adnan Jabbar, Zubair Ahmad

Department of Radiation Oncology

Cerebral metastasis as an initial clinical presentation of prostate carcinoma is extremely rare. Usually, patients have widespread metastasis in the body before presenting with brain metastasis. In the absence of extensive metastasis, especially without bony metastasis, only brain metastasis is an unusual presentation of the disease. We report a case of a 59-years-old patient who presented with a lack of concentration and decreased vision. Magnetic resonance imaging (MRI) of the brain revealed a large right parietal-occipital space-occupying lesion. He underwent surgery and the pathological diagnosis of the tumor turned out to be metastatic prostate carcinoma. Further evaluation by a whole-body …

Analysis Of Candida Auris Fungemia At A Single Facility In Kenya, Rodney Adam, Gunturu Revathi, Nancy Okinda, Melanie Fontaine, Jasmit Shah, Elizabeth Kagotho, Mariana Castanheira, Michael A. Pfaller, Daniel Maina

Pathology, East Africa

Objectives: Candida auris emerged as a human pathogen in 2009 and has subsequently been identified around the world as a cause of invasive candidiasis. We did an analysis from a single institution in order to analyze risk factors and outcomes for C. auris candidemia.

Methods: Patients with candidemia were identified by the electronic medical record and reviewed for risk factors and outcome. Candida isolates were identified by Vitek2 as Candida haemulonii, but species determinations for 21 of the isolates using published molecular and proteomic methods identified all as C. auris.

Findings: From September 2010 to December 2016, C. auris accounted …

Tumor Heterogeneity As A Predictor Of Response To Neoadjuvant Chemotherapy In Locally Advanced Rectal Cancer, Alissa Greenbaum, David R. Martin, Therese J. Bocklage, Ji-Hyun Lee, Scott A. Ness, Ashwani Rajput

Pathology and Laboratory Medicine Faculty Publications

BACKGROUND: Neoadjuvant chemoradiotherapy (nCRT) is the standard of care for locally advanced adenocarcinoma of the rectum, but it is currently unknown which patients have disease that will respond. This study tested the correlation between response to nCRT and intratumoral heterogeneity using next-generation sequencing assays.

PATIENTS AND METHODS: DNA was extracted from formalin-fixed, paraffin-embedded biopsy samples from a cohort of patients with locally advanced rectal adenocarcinoma (T3/4 or N1/2 disease) who received nCRT. High read-depth sequencing of > 400 cancer-relevant genes was performed. Tumor mutations and variant allele frequencies were used to calculate mutant-allele tumor heterogeneity (MATH) scores as measures of intratumoral …

Chimeric Antigen T Cell Receptor Treatment In Hematological Malignancies, Natasha Ali

Department of Pathology and Laboratory Medicine

No abstract provided.

Initial Management Of Meningiomas: Analysis Of The National Cancer Database, Catherine R. Garcia, Stacey A. Slone, Monica Chau, Janna H. Neltner, Thomas A. Pittman, John L. Villano

Neurology Faculty Publications

BACKGROUND: Meningiomas are the most common central nervous system tumor. We describe current trends in treatment and survival using the largest cancer dataset in the United States.

METHODS: We analyzed the National Cancer Database from 2004 to 2014, for all patients with diagnosis of meningioma.

RESULTS: 201,765 cases were analyzed. Patients were most commonly White (81.9%) females (73.2%) with a median age of 64 years. Fifty percent of patients were diagnosed by imaging. Patients were reported as grade I (24.9%), grade II (5.0%), grade III (0.7%), or unknown WHO grade (69.4%). Patients diagnosed by imaging were older, received treatment in …

Blood Film Says It All! Rare Case Of Congenital Ttp Misdiagnosed As Itp, Ayesha Majeed Memon, Natasha Ali

Department of Pathology and Laboratory Medicine

We report a case of a 16-year-old female who presented with bleeding diathesis. Peripheral blood film examination was consistent with microangiopathic hemolytic anemia with 7% fragmented red blood cells. The ADAMTS13 level was 40 ng/ml (reference range: 630-850 ng/ml). She responded to plasma exchange therapy and methylprednisolone and was discharged in a stable condition.

Mutational Landscape Of Head And Neck Squamous Cell Carcinomas In A South Asian Population, Kulsoom Ghias, Sadiq S. Rehmani, Safina Abdul Razzak, Sarosh Madani, M Kamran Azim, Rashida Ahmed, Mumtaz J Khan

Department of Biological & Biomedical Sciences

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer type globally and contributes significantly to burden of disease in South Asia. In Pakistan, HNSCC is anmong the most commonly diagnosed cancer in males and females. The increasing regional burden of HNSCC along with a unique set of risk factors merited a deeper investigation of the disease at the genomic level. Whole exome sequencing of HNSCC samples and matched normal genomic DNA (n=7) was performed. Significant somatic single nucleotide variants (SNVs) were identified and pathway analysis performed to determine frequently affected signaling pathways. We identified significant, novel …