Nox2-Derived Oxidative Stress Results In Inefficacy Of Antibiotics Against Post-Influenza S. Aureus Pneumonia., 2016 University of Nebraska Medical Center
Nox2-Derived Oxidative Stress Results In Inefficacy Of Antibiotics Against Post-Influenza S. Aureus Pneumonia., Keer Sun, Vijaya Kumar Yajjala, Christopher Bauer, G. Talmon, Karl J. Fischer, Tammy Kielian, Dennis W. Metzger
Journal Articles: Pathology and Microbiology
Clinical post-influenza Staphylococcus aureus pneumonia is characterized by extensive lung inflammation associated with severe morbidity and mortality even after appropriate antibiotic treatment. In this study, we show that antibiotics rescue nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 (Nox2)-deficient mice but fail to fully protect WT animals from influenza and S. aureus coinfection. Further experiments indicate that the inefficacy of antibiotics against coinfection is attributable to oxidative stress-associated inflammatory lung injury. However, Nox2-induced lung damage during coinfection was not associated with aggravated inflammatory cytokine response or cell infiltration but rather caused by reduced survival of myeloid cells. Specifically, oxidative stress ...
Classic Virilizing Congenital Adrenal Hyperplasia Presenting Late: Case Series From Pakistan, 2016 Aga Khan University
Classic Virilizing Congenital Adrenal Hyperplasia Presenting Late: Case Series From Pakistan, Aysha Habib Khan, Muniba Aban, Rameez-Ul-Hassan, Naeem-Ul-Haq, Jamal Raza, Abdul Jabbar, Tariq Moatter
Aysha Habib Khan
Deficiency of 21 hydroxylase enzyme deficiency (21OH) activity accounts for 90% cases of congenital adrenal hyperplasia (CAH). This results in deficient cortisol, increased ACTH, adrenal hyperplasia and increased adrenal androgen secretion. There is marked virilization in genetic females which is the hallmark of this disorder. Genetic heterogeneity in 21 OHD is well recognized, and both severe and mild forms occur. We present three cases of adult females with the disease from a larger study to establish genotype, phenotype correlation of Pakistani patients with congenital adrenal hyperplasia (CAH) and to highlight issues such as diagnostic delay, inappropriate gender assignment at birth ...
P27kip1 And P130 Cooperate To Regulate Hematopoietic Cell Proliferation In Vivo, 2016 Hammersmith Hospital
P27kip1 And P130 Cooperate To Regulate Hematopoietic Cell Proliferation In Vivo, Inês Soeiro, Azim Mohamedali, Hanna M. Romanska, Nicholas C. Lea, Emma S. Child, Janet Glassford, Stephen J. Orr, Claudia Roberts, Kikkeri N. Naresh, El-Nasir Lalani, David J. Mann, Roger J. Watson, N. Shaun B. Thomas, Eric W. -F. Lam
El Nasir Lalani
To investigate the potential functional cooperation between p27Kip1 and p130 in vivo, we generated mice deficient for both p27Kip1 and p130. In p27Kip1−/−;p130−/− mice, the cellularity of the spleens but not the thymi is significantly increased compared with that of their p27Kip1−/− counterparts, affecting the lymphoid, erythroid, and myeloid compartments. In vivo cell proliferation is significantly augmented in the B and T cells, monocytes, macrophages, and erythroid progenitors in the spleens of p27Kip1−/−; p130−/− animals. Immunoprecipitation and immunodepletion studies indicate that p130 can compensate for the absence of p27Kip1 in binding to and ...
Topographical Expression Of Class Ia And Class Ii Phosphoinositide 3-Kinase Enzymes In Normal Human Tissues Is Consistent With A Role In Differentiation, 2016 Imperial College School of Medicine
Topographical Expression Of Class Ia And Class Ii Phosphoinositide 3-Kinase Enzymes In Normal Human Tissues Is Consistent With A Role In Differentiation, Soha Salama El Sheikh, Jan Domin, Prakitpunthu Tomtitchong, Paul Abel, Gordon Stamp, El-Nasir Lalani
El Nasir Lalani
Background: Growth factor, cytokine and chemokine-induced activation of PI3K enzymes constitutes the start of a complex signalling cascade, which ultimately mediates cellular activities such as proliferation, differentiation, chemotaxis, survival, trafficking, and glucose homeostasis. The PI3K enzyme family is divided into 3 classes; class I (subdivided into IA and IB), class II (PI3K-C2α, PI3K-C2β and PI3K-C2γ) and class III PI3K. Expression of these enzymes in human tissue has not been clearly defined.
Methods: In this study, we analysed the immunohistochemical topographical expression profile of class IA (anti-p85 adaptor) and class II PI3K (PI3K-C2α and PI3K-C2β) enzymes in 104 formalin-fixed, paraffin embedded ...
Molecular And Cellular Biology Of Prostate Cancer, 2016 Aga Khan University
Molecular And Cellular Biology Of Prostate Cancer, El-Nasir Lalani, Marc Elie Laniado, Paul David Abel
El Nasir Lalani
Prostate cancer is an enigmatic disease. Although prostatic-intraepithelial neoplasia appears as early as the third decade and as many as 80% of 80 year old men have epithelial cells in their prostate that fit the morphological criteria for cancer, only about 10% of men will ever have the clinical disease and less than 3% will die from it. There have been no significant proven interventions which have altered the natural history of the disease since hormone down regulation was introduced in the 1940s and new research has been poorly supported. There is however an urgent need to develop new criteria ...
Body And Organ Measurements In Infants And Neonates: An Autopsy Study, 2016 The University of Western Ontario
Body And Organ Measurements In Infants And Neonates: An Autopsy Study, Audrey-Ann M. Evetts
Electronic Thesis and Dissertation Repository
Introduction: A pathologist doing a pediatric autopsy will commonly assess child’s development by comparing the postmortem data to standardized population parameters using body and organ measurement charts. Although a number of resources are available, many are outdated and have significant limitations.
Objectives: To create Ontario population-specific organ and body measurement mean charts for infants and to explore relationships between body measurements/organ weights and cause of death, age, and gender of the deceased.
Methods: A database of 900 cases of infant and neonatal deaths that were investigated by Ontario coroners from 2000 to 2010 was retrospectively analyzed.
Multiple Sclerosis Patients Have A Distinct Gut Microbiota Compared To Healthy Controls, Jun Chen, Nicholas Chia, Krishna R Kalari, Janet Z Yao, Martina Novotna, M Mateo Paz Soldan, David H Luckey, Eric V Marietta, Patricio R Jeraldo, Xianfeng Chen, Brian G Weinshenker, Moses Rodriguez, Orhun H Kantarci, Heidi Nelson, Joseph A Murray, Ashutosh K Mangalam
Department of Pathology Publications
Multiple sclerosis (MS) is an immune-mediated disease, the etiology of which involves both genetic and environmental factors. The exact nature of the environmental factors responsible for predisposition to MS remains elusive; however, it's hypothesized that gastrointestinal microbiota might play an important role in pathogenesis of MS. Therefore, this study was designed to investigate whether gut microbiota are altered in MS by comparing the fecal microbiota in relapsing remitting MS (RRMS) (n = 31) patients to that of age- and gender-matched healthy controls (n = 36). Phylotype profiles of the gut microbial populations were generated using hypervariable tag sequencing of the V3-V5 ...
Histological And Molecular Analysis Of A Progressive Diffuse Intrinsic Pontine Glioma And Synchronous Metastatic Lesions: A Case Report., 2016 George Washington University
Histological And Molecular Analysis Of A Progressive Diffuse Intrinsic Pontine Glioma And Synchronous Metastatic Lesions: A Case Report., Javad Nazarian, Gary E Mason, Cheng Ying Ho, Eshini Panditharatna, Madhuri Kambhampati, Louis Gilbert Vezina, Roger J. Packer, Eugene I Hwang
Integrative Systems Biology Faculty Publications
There is no curative treatment for patients with diffuse intrinsic pontine glioma (DIPG). However, with the recent availability of biopsy and autopsy tissue, new data regarding the biologic behavior of this tumor have emerged, allowing greater molecular characterization and leading to investigations which may result in improved therapeutic options. Treatment strategies must address both primary disease sites as well as any metastatic deposits, which may be variably sensitive to a particular approach.In this case report, we present a patient with DIPG treated with irradiation and serial investigational agents. The clinical, pathological and molecular phenotypes of both the progressive primary ...
5-Hyroxymethylcytosine Immunohistochemical Staining Correlates With Overall Survival In Patients With Chronic Myelomonocytic Leukemia, 2016 University of Massachusetts Medical School
5-Hyroxymethylcytosine Immunohistochemical Staining Correlates With Overall Survival In Patients With Chronic Myelomonocytic Leukemia, William Selove, Karen A. Dresser, Benjamin Chen
UMass Center for Clinical and Translational Science Research Retreat
Introduction Chronic myelomonocytic leukemia (CMML) is a myelodysplastic/myeloproliferative neoplasm that has been associated with a number of genetic mutations, most commonly TET2 mutations in up to 50-60% of cases. Mutations in epigenetic genes such as TET2 are known to disrupt the conversion of 5-methycytosine to 5-hydroxymethylcytosine (5hmC), contributing to oncogenesis. We hypothesized that CMML cases would exhibit decreased 5hmC expression, reflecting the propensity for TET2 mutations in CMML. We also sought to determine whether 5hmC IHC status reflected disease severity in terms of progression to AML and overall patient survival.
Methods Thirty-five cases of CMML from between 1/2006 ...
An Intact Dissecting Baker's Cyst Mimicking Recurrent Deep Vein Thrombosis, 2016 University of Massachusetts Medical School
An Intact Dissecting Baker's Cyst Mimicking Recurrent Deep Vein Thrombosis, Sarah Jamshed, L. Michael Snyder
Open Access Articles
We report a case of a 75-year-old female with a history of acute deep vein thrombosis (DVT) 6 years ago who presented with unilateral calf swelling and pain. D-dimer was normal, and compression ultrasound revealed findings typical of DVT, including an incompressible dilated and hypoechoic peroneal vein. Despite 4 months of anticoagulation for supposed recurrent DVT, pain symptoms persisted and repeat D-dimer and compression ultrasound were unchanged. A magnetic resonance imaging scan to investigate the leg demonstrated a 6-cm dissecting Baker's cyst extending posterolaterally resulting in venous compression and distal dilation, which appeared to have been confused with a ...
Inflammatory Cytokine Signaling Contributes To Erlotinib Resistance In Head And Neck Squamous Cell Carcinoma, Aditya Stanam
Theses and Dissertations
Resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) is a major obstacle in the success of head and neck cancer therapy. Despite efforts by several groups to understand the mechanisms of resistance to tyrosine kinase inhibitors such as erlotinib, there has been little success in improving the patient survival. Given that there are a number of ongoing clinical trials testing the efficacy of erlotinib in head and neck cancer, it is essential to investigate the novel mechanisms of erlotinib resistance to improve its efficacy and patient survival. This dissertation addresses this issue of erlotinib resistance in head ...
Moving Towards Effective Therapeutic Strategies For Neuronal Ceroid Lipofuscinosis., 2016 Sanford Research
Moving Towards Effective Therapeutic Strategies For Neuronal Ceroid Lipofuscinosis., Ryan D. Geraets, Seung Yon Koh, Michelle L. Hastings, Tammy Kielian, David A. Pearce, Jill M. Weimer
Journal Articles: Pathology and Microbiology
The Neuronal Ceroid Lipofuscinoses (NCLs) are a family of autosomal recessive neurodegenerative disorders that annually affect 1:100,000 live births worldwide. This family of diseases results from mutations in one of 14 different genes that share common clinical and pathological etiologies. Clinically, the diseases are subcategorized into infantile, late-infantile, juvenile and adult forms based on their age of onset. Though the disease phenotypes may vary in their age and order of presentation, all typically include progressive visual deterioration and blindness, cognitive impairment, motor deficits and seizures. Pathological hallmarks of NCLs include the accumulation of storage material or ceroid in ...
Labrad : Vol 42, Issue 1 - March 2016, 2016 Aga Khan University
Labrad : Vol 42, Issue 1 - March 2016, Aga Khan University Hospital, Karachi
- Biochemical Bone Profiles Available at Clinical Laboratoryof Aga Khan University Hospital
- Ionized Calcium Determination in Clinical Labortory
- Parathyroid Hormone Disorders and Issues of Testing
- Tubular Maximum Reabsorption Rate of Phosphate to Glomerular Filtration Rate (TmP/GFR)
- Renal Osteodystrophy: A Disturbed Metabolic Aspect of Renal Failure
- Update on Microbiological Diagnosis of Bone and Joint Disorders
- Classification of Tumours of Bone : An Update Based on the 2013 World Health Organization Classification of Tumours of Soft Tissue and Bone
- Recent Developments in Benign Bone Tumours
- Role of Clinical and Radiological Correlation in Orthopaedic Pathology
- CME Seminar on ‘World Osteoporosis Day’
Intimin Likely Used To Cause Disease During Competition With Commensal Escherichia Coli, 2016 Liberty University
Intimin Likely Used To Cause Disease During Competition With Commensal Escherichia Coli, Dominique J. Richburg
Senior Honors Theses
The intimin gene in the Locus of Enterocyte Effacement (LEE) island of pathogenicity is the primary attachment mechanism in Citrobacter rodentium. Intimin is a bacterial adhesin (protein) that attaches to obtain a niche/nutrient and thrive within the intestine. Intimin was deleted within C. rodentium to study colonization and pathogenesis in the murine intestine. Additionally, C. rodentium is an attaching/effacing pathogen, and a useful murine model in understanding Enterohemorrhagic Escherichia coli (EHEC) infection in humans. E. coli and C. rodentium cause gastroenteritis in humans and mice, respectively. C. rodentium is a murine pathogen commonly used to model gastrointestinal disease ...
A Novel Comparative Pattern Analysis Approach Identifies Chronic Alcohol Mediated Dysregulation Of Transcriptomic Dynamics During Liver Regeneration., 2016 Thomas Jefferson University, Daniel Baugh Institute for Functional Genomics and Computational Biology, Department of Pathology, Anatomy and Cell Biology
A Novel Comparative Pattern Analysis Approach Identifies Chronic Alcohol Mediated Dysregulation Of Transcriptomic Dynamics During Liver Regeneration., Lakshmi Kuttippurathu, Egle Juskeviciute, Rachael P Dippold, Jan B. Hoek, Rajanikanth Vadigepalli
Department of Pathology, Anatomy and Cell Biology Faculty Papers
BACKGROUND: Liver regeneration is inhibited by chronic ethanol consumption and this impaired repair response may contribute to the risk for alcoholic liver disease. We developed and applied a novel data analysis approach to assess the effect of chronic ethanol intake in the mechanisms responsible for liver regeneration. We performed a time series transcriptomic profiling study of the regeneration response after 2/3(rd) partial hepatectomy (PHx) in ethanol-fed and isocaloric control rats.
RESULTS: We developed a novel data analysis approach focusing on comparative pattern counts (COMPACT) to exhaustively identify the dominant and subtle differential expression patterns. Approximately 6500 genes were ...
Kshv-Encoded Vil-6 Collaborates With Deregulated C-Myc To Drive Plasmablastic Neoplasms In Mice, 2016 University of Iowa
Kshv-Encoded Vil-6 Collaborates With Deregulated C-Myc To Drive Plasmablastic Neoplasms In Mice, T R Rosean, C J Holman, V S Tompkins, X Jing, M D Krasowski, S Rose-John, S Janz
Department of Pathology Publications
No abstract provided.
How Our Practice Of Histopathology, Especially Tumour Pathology Has Changed In The Last Two Decades: Reflections From A Major Referral Center In Pakistan, Ahmad Z, Idrees R, Fatima S, Arshad H, Din Nu, Memon A, Minhas K, Ahmed A, Fatima S, Arif M, Ahmed R, Haroon S, Shahid Pervez, Hassan S, Kayani N
Continued advances in the field of histo-pathology (and cyto-pathology) over the past two decades have resulted in dramatic changes in the manner in which these disciplines are now practiced. This is especially true in the setting of a large university hospital where the role of pathologists as clinicians (diagnosticians), undergraduate and postgraduate educators, and researchers has evolved considerably. The world around us has changed significantly during this period bringing about a considerable change in our lifestyles and the way we live. This is the world of the internet and the world-wide web, the world of Google and Wikipedia, of Youtube ...
The Pathology Of The Feline Model Of Mucopolysaccharidosis Vi, 2016 University of Pennsylvania
The Pathology Of The Feline Model Of Mucopolysaccharidosis Vi, Mark Haskins, Gustavo Aguirre, Peter Jezyk, Donald Patterson
Gustavo D. Aguirre, VMD, PhD
Three cats with feline arylsulfatase-B-deficient mucopolysaccharidosis were studied by light and transmission electron microscopy. Membrane-bound cytoplasmic inclusions were present in hepatocytes, bone marrow granulocytes, vascular smooth muscle cells, and fibroblasts in skin, cornea, and cardiac valves. Central nervous system lesions were restricted to mild ventricular dilatation, perithelial cell vacuolation, and, in one animal, cord compression by vertebral exostoses. The lesions in these cats closely resembled those described in human patients with mucopolysaccharidosis VI (Maroteaux-Lamy syndrome).
Spectrum Of Microbial Diseases And Resistance Patterns At A Private Teaching Hospital In Kenya: Implications For Clinical Practice, Daniel Maina, Geoffrey Omuse, Gunturu Revathi, Rodney Adam
Pathology, East Africa
Background: Accurate local prevalence of microbial diseases and microbial resistance data are vital for optimal treatment of patients. However, there are few reports of these data from developing countries, especially from sub-Saharan Africa. The status of Aga Khan University Hospital Nairobi as an internationally accredited hospital and a laboratory with an electronic medical record system has made it possible to analyze local prevalence and antimicrobial susceptibility data and compare it with other published data.
Methods: We have analyzed the spectrum of microbial agents and resistance patterns seen at a 300 bed tertiary private teaching hospital in Kenya using microbial identity ...
Multiplatform Molecular Profiling Identifies Potentially Targetable Biomarkers In Malignant Phyllodes Tumors Of The Breast., 2016 Caris Life Sciences, Phoenix, AZ, United States
Multiplatform Molecular Profiling Identifies Potentially Targetable Biomarkers In Malignant Phyllodes Tumors Of The Breast., Zoran Gatalica, Semir Vranic, Anatole Ghazalpour, Joanne Xiu, Idris Tolgay Ocal, John Mcgill, Ryan P Bender, Erin Discianno, Aaron Schlum, Souzan Sanati, Juan P. Palazzo, Sandeep Reddy, Barbara Pockaj
Department of Pathology, Anatomy and Cell Biology Faculty Papers
Malignant phyllodes tumor is a rare breast malignancy with sarcomatous overgrowth and with limited effective treatment options for recurrent and metastatic cases. Recent clinical trials indicated a potential for anti-angiogenic, anti-EGFR and immunotherapeutic approaches for patients with sarcomas, which led us to investigate these and other targetable pathways in malignant phyllodes tumor of the breast. Thirty-six malignant phyllodes tumors (including 8 metastatic tumors with two cases having matched primary and metastatic tumors) were profiled using gene sequencing, gene copy number analysis, whole genome expression, and protein expression. Whole genome expression analysis demonstrated consistent over-expression of genes involved in angiogenesis including ...