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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 2016 Mayo Clinic

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., Javad Nazarian, Gary E Mason, Cheng Ying Ho, Eshini Panditharatna, Madhuri Kambhampati, Louis Gilbert Vezina, Roger J. Packer, Eugene I Hwang 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, William Selove, Karen A. Dresser, Benjamin Chen 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 ...


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 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 ...


Intimin Likely Used To Cause Disease During Competition With Commensal Escherichia Coli, Dominique J. Richburg 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., Lakshmi Kuttippurathu, Egle Juskeviciute, Rachael P Dippold, Jan B. Hoek, Rajanikanth Vadigepalli 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, T R Rosean, C J Holman, V S Tompkins, X Jing, M D Krasowski, S Rose-John, S Janz 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 2016 Aga Khan University

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

Shahid Pervez

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, Mark Haskins, Gustavo Aguirre, Peter Jezyk, Donald Patterson 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).


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 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 ...


T Cell/Histiocyte-Rich Large B Cell Lymphoma Of The Thymus: A Diagnostic Pitfall., Jie Xu, Xiaojun Wu, Vishnu Reddy 2016 George Washington University

T Cell/Histiocyte-Rich Large B Cell Lymphoma Of The Thymus: A Diagnostic Pitfall., Jie Xu, Xiaojun Wu, Vishnu Reddy

Pathology Faculty Publications

T cell/histiocyte-rich large B cell lymphoma (THRLBCL) is predominantly a nodal disease, with extranodal involvement, such as bone marrow, spleen, and liver. However, primary THRLBCL has never been reported in the thymus in the English literature. Here we report a case of THRLBCL presenting as mediastinal mass and lymphadenopathy. Based on the frozen section diagnosis of "thymoma," a 12 cm mass was excised. A year later she developed multiple enlarged lymph nodes and pulmonary nodules. Consultant review of the excised mediastinal mass showed scattered large atypical cells that were CD20+ and PAX-5+ and negative for pan-cytokeratin, AE1, and AE3 ...


Metataxonomic And Metagenomic Approaches Vs. Culture-Based Techniques For Clinical Pathology., Sarah K. Hilton, Eduardo Castro-Nallar, Marcos Pérez-Losada, Ian Toma, Timothy A. McCaffrey, Eric P. Hoffman, Marc O. Siegel, Gary L. Simon, W. Evan Johnson, Keith Crandall 2016 George Washington University

Metataxonomic And Metagenomic Approaches Vs. Culture-Based Techniques For Clinical Pathology., Sarah K. Hilton, Eduardo Castro-Nallar, Marcos Pérez-Losada, Ian Toma, Timothy A. Mccaffrey, Eric P. Hoffman, Marc O. Siegel, Gary L. Simon, W. Evan Johnson, Keith Crandall

Integrative Systems Biology Faculty Publications

Diagnoses that are both timely and accurate are critically important for patients with life-threatening or drug resistant infections. Technological improvements in High-Throughput Sequencing (HTS) have led to its use in pathogen detection and its application in clinical diagnoses of infectious diseases. The present study compares two HTS methods, 16S rRNA marker gene sequencing (metataxonomics) and whole metagenomic shotgun sequencing (metagenomics), in their respective abilities to match the same diagnosis as traditional culture methods (culture inference) for patients with ventilator associated pneumonia (VAP). The metagenomic analysis was able to produce the same diagnosis as culture methods at the species-level for five ...


The Experience Of Being Unsheltered In Atlanta, Ikeranda Smith 2016 Walden University

The Experience Of Being Unsheltered In Atlanta, Ikeranda Smith

Walden Dissertations and Doctoral Studies

In the United States, it is estimated that millions of adults are homeless. Some individuals choose not to use homeless shelters or are ineligible for their use. Researchers have indicated that many unsheltered homeless are men over the age of 45 years. The purpose of this phenomenological study was to examine the experiences with social services providers among unsheltered men. Understanding the social networks of unsheltered homeless and the use of spirituality or faith as a resource for coping was also examined, as a significant gap exists in the research on unsheltered homeless. Face-to-face, in-depth interviews were conducted with 8 ...


Tmsb4y Is A Candidate Tumor Suppressor On The Y Chromosome And Is Deleted In Male Breast Cancer., Hong Yuen Wong, Grace M Wang, Sarah Croessmann, Daniel J Zabransky, Anita Aggarwal, Min-Ling Liu, + 10 more 2015 George Washington University

Tmsb4y Is A Candidate Tumor Suppressor On The Y Chromosome And Is Deleted In Male Breast Cancer., Hong Yuen Wong, Grace M Wang, Sarah Croessmann, Daniel J Zabransky, Anita Aggarwal, Min-Ling Liu, + 10 More

Pathology Faculty Publications

Male breast cancer comprises less than 1% of breast cancer diagnoses. Although estrogen exposure has been causally linked to the development of female breast cancers, the etiology of male breast cancer is unclear. Here, we show via fluorescence in situ hybridization (FISH) and droplet digital PCR (ddPCR) that the Y chromosome was clonally lost at a frequency of ~16% (5/31) in two independent cohorts of male breast cancer patients. We also show somatic loss of the Y chromosome gene TMSB4Y in a male breast tumor, confirming prior reports of loss at this locus in male breast cancers. To further ...


Midgut Barrier Imparts Selective Resistance To Filarial Worm Infection In Culex Pipiens Pipiens, Michelle Michalski, Sarah Erickson, Bruce Christensen, Lyric Bartholomay 2015 University of Wisconsin–Oshkosh

Midgut Barrier Imparts Selective Resistance To Filarial Worm Infection In Culex Pipiens Pipiens, Michelle Michalski, Sarah Erickson, Bruce Christensen, Lyric Bartholomay

Lyric C. Bartholomay

Mosquitoes in the Culex pipiens complex thrive in temperate and tropical regions worldwide, and serve as efficient vectors of Bancroftian lymphatic filariasis (LF) caused by Wuchereria bancrofti in Asia, Africa, the West Indies, South America, and Micronesia. However, members of this mosquito complex do not act as natural vectors for Brugian LF caused by Brugia malayi, or for the cat parasite B. pahangi, despite their presence in South Asia where these parasites are endemic. Previous work with the Iowa strain of Culex pipiens pipiens demonstrates that it is equally susceptible to W. bancrofti as is the natural Cx. p. pipiens ...


Midgut Barrier Imparts Selective Resistance To Filarial Worm Infection In Culex Pipiens Pipiens, Michelle Michalski, Sarah Erickson, Bruce Christensen, Lyric Bartholomay 2015 University of Wisconsin–Oshkosh

Midgut Barrier Imparts Selective Resistance To Filarial Worm Infection In Culex Pipiens Pipiens, Michelle Michalski, Sarah Erickson, Bruce Christensen, Lyric Bartholomay

Lyric Bartholomay

Mosquitoes in the Culex pipiens complex thrive in temperate and tropical regions worldwide, and serve as efficient vectors of Bancroftian lymphatic filariasis (LF) caused by Wuchereria bancrofti in Asia, Africa, the West Indies, South America, and Micronesia. However, members of this mosquito complex do not act as natural vectors for Brugian LF caused by Brugia malayi, or for the cat parasite B. pahangi, despite their presence in South Asia where these parasites are endemic. Previous work with the Iowa strain of Culex pipiens pipiens demonstrates that it is equally susceptible to W. bancrofti as is the natural Cx. p. pipiens ...


Labrad : Vol 41, Issue 3 - December 2015, Aga Khan University Hospital, Karachi 2015 Aga Khan University

Labrad : Vol 41, Issue 3 - December 2015, Aga Khan University Hospital, Karachi

LABRAD

  • Overview on Approach to Inherited Bleeding Disorders
  • Diagnostic Approach to Haemoglobinopathies
  • Transient Abnormal Myelopoiesis
  • Urinary Tract Infections (UTI) in Children
  • Role of Histopathology in the Diagnosis of Paediatric Renal Tumours
  • Role of Histopathology in the Diagnosis of Paediatric Bone and Soft Tissue Small Round Cell Tumours
  • Evaluation of Inborn Errors of Metabolism (IEM) In a Nutshell
  • An Update on Blood Lead Levels in Children
  • Clinical Utility of Immature Platelet Fraction – An advanced 25 Parameter in Laboratory Hematology
  • Meeting Report: “Les Confluences” The Society for the Study 30 of Inborn errors of Metabolism (SSIEM) Annual Symposium 2015 in Lyon, France


Intraventricular Sialidase Administration Enhances Gm1 Ganglioside Expression And Is Partially Neuroprotective In A Mouse Model Of Parkinson's Disease., Jay S Schneider, Thomas N Seyfried, Hyo-S Choi, Sarah Kidd 2015 Department of Pathology Anatomy and Cell Biology, Thomas Jefferson University

Intraventricular Sialidase Administration Enhances Gm1 Ganglioside Expression And Is Partially Neuroprotective In A Mouse Model Of Parkinson's Disease., Jay S Schneider, Thomas N Seyfried, Hyo-S Choi, Sarah Kidd

Department of Pathology, Anatomy and Cell Biology Faculty Papers

BACKGROUND: Preclinical and clinical studies have previously shown that systemic administration of GM1 ganglioside has neuroprotective and neurorestorative properties in Parkinson's disease (PD) models and in PD patients. However, the clinical development of GM1 for PD has been hampered by its animal origin (GM1 used in previous studies was extracted from bovine brains), limited bioavailability, and limited blood brain barrier penetrance following systemic administration.

OBJECTIVE: To assess an alternative therapeutic approach to systemic administration of brain-derived GM1 to enhance GM1 levels in the brain via enzymatic conversion of polysialogangliosides into GM1 and to assess the neuroprotective potential of this ...


A Small Molecule Inhibitor Of Itk And Rlk Impairs Th1 Differentiation And Prevents Colitis Disease Progression, Hyoung-Soo Cho, HyunMu Shin, Helena Haberstock-Debic, Yan Xing, Timothy D. Owens, Jens Oliver. Funk, Ronald J. Hill, J. Michael Bradshaw, Leslie J. Berg 2015 University of Massachusetts Medical School

A Small Molecule Inhibitor Of Itk And Rlk Impairs Th1 Differentiation And Prevents Colitis Disease Progression, Hyoung-Soo Cho, Hyunmu Shin, Helena Haberstock-Debic, Yan Xing, Timothy D. Owens, Jens Oliver. Funk, Ronald J. Hill, J. Michael Bradshaw, Leslie J. Berg

Open Access Articles

In T cells, the Tec kinases IL-2-inducible T cell kinase (ITK) and resting lymphocyte kinase (RLK) are activated by TCR stimulation and are required for optimal downstream signaling. Studies of CD4(+) T cells from Itk(-/-) and Itk(-/-)Rlk(-/-) mice have indicated differential roles of ITK and RLK in Th1, Th2, and Th17 differentiation and cytokine production. However, these findings are confounded by the complex T cell developmental defects in these mice. In this study, we examine the consequences of ITK and RLK inhibition using a highly selective and potent small molecule covalent inhibitor PRN694. In vitro Th polarization experiments indicate ...


Expression Of Human Kallikrein Protein And Mrna In Maxillofacial Cysts And Tumours, Karl Kevin Cuddy 2015 The University of Western Ontario

Expression Of Human Kallikrein Protein And Mrna In Maxillofacial Cysts And Tumours, Karl Kevin Cuddy

Electronic Thesis and Dissertation Repository

Non-inflammatory odontogenic cysts and tumours vary in clinical appearance and can cause widespread destruction and deformation of the face. Proteases may play a role in the differing pathogenesis of these cysts and tumours. Human kallikrein proteins (KLKs) are a group of 15 serine proteases implicated in a variety of signaling and regulatory roles. This study evaluated the ameloblastoma, keratocystic odontogenic tumour (KOT), dentigerous cyst, lateral periodontal cyst, nasopalatine duct cyst and odontoma for the presence of KLK 3, 4, 5, 9 and 11 utilizing immunohistochemistry. Secondarily, we evaluated ameloblastoma for expression of KLK 1-15 mRNA using reverse transcription-polymerase chain reaction ...


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