Life Sciences Commons^™

Tryptophan 375 Stabilizes The Outer-Domain Core Of Gp120 For Hiv Vaccine Immunogen Design, Duoyi Hu, Dane Bowder, Wenzhong Wei, Jesse Thompson, Mark A. Wilson, Shi-Hua Xiang

Nebraska Center for Virology: Faculty Publications

The outer-domain core of gp120 may serve as a better HIV vaccine immunogen than the full-length gp120 because of its greater stability and immunogenicity. In our previous report, we introduced two disulfide bonds to the outer-domain core of gp120 to fix its conformation into a CD4-bound state, which resulted in a significant increase in its immunogenicity when compared to the wild-type outer-domain core. In this report, to further improve the immunogenicity of the outer-domain core based immunogen, we have introduced a Tryptophan residue at gp120 amino acid sequence position 375 (375S/W). Our data from immunized guinea pigs indeed shows a …

Chloroviruses Have A Sweet Tooth, James L. Van Etten, Irina V. Agarkova, David D. Dunigan, Michela Tonetti, Cristina De Castro, Garry A. Duncan

Nebraska Center for Virology: Faculty Publications

Chloroviruses are large double-stranded DNA (dsDNA) viruses that infect certain isolates of chlorella-like green algae. They contain up to approximately 400 protein-encoding genes and 16 transfer RNA (tRNA) genes. This review summarizes the unexpected finding that many of the chlorovirus genes encode proteins involved in manipulating carbohydrates. These include enzymes involved in making extracellular polysaccharides, such as hyaluronan and chitin, enzymes that make nucleotide sugars, such as GDP-L-fucose and GDP-D-rhamnose and enzymes involved in the synthesis of glycans attached to the virus major capsid proteins. This latter process differs from that of all other glycoprotein containing viruses that traditionally use …

Characterization Of A New Chlorovirus Type With Permissive And Non-Permissive Features On Phylogenetically Related Algal Strains, Cristian F. Quispe, Ahmed Esmael, Olivia Sonderman, Michelle Mcquinn, Irina Agarkova, Mohammed Battah, Garry A. Duncan, David D. Dunigan, Timothy P. L. Smith, Cristina Decastro, Immacolata Speciale, Fangrui Ma, James L. Van Etten

Nebraska Center for Virology: Faculty Publications

A previous report indicated that prototype chlorovirus PBCV-1 replicated in two Chlorella variabilis algal strains, NC64A and Syngen 2-3, that are ex-endosymbionts isolated from the protozoan Paramecium bursaria. Surprisingly, plaque-forming viruses on Syngen 2-3 lawns were often higher than on NC64A lawns from indigenous water samples. These differences led to the discovery of viruses that exclusively replicate in Syngen 2-3 cells, named Only Syngen (OSy) viruses. OSy-NE5, the prototype virus for the proposed new species, had a linear dsDNA genome of 327 kb with 44-nucleotide-long, incompletely base-paired, covalently closed hairpin ends. Each hairpin structure was followed by an identical …

Traumatic Stab Wound To The Chest: A Rare Cause Of Pituitary Apoplexy, Jairo Espinosa M.D., Tim Wysozan, Chris Sloffer

Research Day

INTRODUCTION: Pituitary apoplexy is an uncommon condition that results from infarction and hemorrhage of an established pituitary adenoma. Based on our review of the literature, this is the first description of pituitary apoplexy presenting after a knife stab wound to the deltopectoral region. 
CASE PRESENTATION: A 44 year-old male presented to the trauma bay as a tier 1 trauma activation status post stabbing to the left deltopectoral groove. The patient was found to be hypotensive, tachycardic and actively exsanguinating from the stab wound. He was taken to the operating room where the wound was explored and the left cephalic vein …

Phenotypic Low-Level Isoniazid Resistance As A Marker To Predict Ethionamide Resistance In Mycobacterium Tuberculosis, Salima Qamar, Joveria Q. Farooqi, Kausar Jabeen, Rumina Hasan

Department of Pathology and Laboratory Medicine

Background: Tuberculosis is one of the most prevalent diseases in Pakistan. Pakistan has the highest burden of MDR-TB in the Eastern Mediterranean region. Ethionamide is an anti-tuberculous drug frequently used to treat MDR-TB. Its drug susceptibility testing is not easily available in resource limited settings. Since it acts on the same target protein as isoniazid (inhA protein encoded by inhA gene), we sought to find out if phenotypic isoniazid resistance can be a marker of ethionamide resistance.
Materials and Methods: This was a retrospective observational study conducted at the Aga Khan University hospital section of microbiology. Data was retrieved between …

Utility Of Peripheral Film Findings And Its Correlation With Automated Analyzer - An Audit From Tertiary Care Hospital, Sidra Asad, Imran Ahmed, Natasha Ali

Department of Pathology and Laboratory Medicine

Background and Objective: With the advent of automated hematology analyzer, the use of traditional microscopy of blood film has become limited. The objective of our study was to determine the percentage of peripheral blood smear review in our institution in the era of automation and to identify reasons of manual review.
Materials and Methods: This was a prospective audit from January 1, 2015, to January 15, 2015. Consecutive complete blood count (CBC) samples and peripheral smear requests made up the sample size. All age groups and genders were included. CBCs were performed on Sysmex XE-5000. The variables to be analyzed …

Papillary Craniopharyngioma: A Clinicopathologic Study Of A Rare Entity From A Major Tertiary Care Center In Pakistan, Muhammad Usman Tariq, Nasir Ud Din, Zubair Ahmad, Wasim Memon

Department of Pathology and Laboratory Medicine

Background: Papillary craniopharyngioma (PCP) are uncommon variants of craniopharyngiomas (CP), which are benign epithelial neoplasms of the sellar and suprasellar region. Histologically, PCPs are typically composed of well-differentiated stratified squamous epithelium; however, focal variations are not uncommon. A distinction from other lesions of the region, despite being difficult to achieve due to the overlapping radiological and clinical features, is important for adequate treatment to be administered.
Objective: Our aim was to study the clinical and histological features of PCP with emphasis on features that are helpful in its distinction from other lesions that are similar in appearance.
Materials and Methods: …

Rapid Detection Of In Vitro Antituberculous Drug Resistance Among Smear-Positive Respiratory Samples Using Microcolony Detection-Based Direct Drug Susceptibility Testing Method, Irim Iftikhar, Seema Irfan, Joveria Farooqi, Zahida Azizullah, Rumina Hasan

Department of Pathology and Laboratory Medicine

Background: With the rise in multidrug-resistant tuberculosis, there is a search for newer techniques that will rapidly detect drug-resistant Mycobacterium tuberculosis. Although molecular techniques can detect resistance, culture is still considered gold standard, especially in resource-limited settings where quick, cheap, and easy techniques are needed. The aim of the study was to evaluate microcolony method thin layer agar (TLA) for quick detection of resistance against the first- and second-line antituberculous drugs in clinical isolates. This was a cross-sectional study performed at Aga Khan University Hospital.
Material and Methods: A total of 87 Z-N stain smear-positive pulmonary samples were received and …

Mammary Extracellular Matrix Directs Differentiation Of Testicular And Embryonic Stem Cells To Form Functional Mammary Glands In Vivo, Robert D. Bruno, Jodie M. Fleming, Andrea L. George, Corinne A. Boulanger, Pepper Schedin, Gilbert H. Smith

School of Medical Diagnostics & Translational Sciences Faculty Publications

Previously, we demonstrated the ability of the normal mammary microenvironment (niche) to direct non-mammary cells including testicular and embryonic stem cells (ESCs) to adopt a mammary epithelial cell (MEC) fate. These studies relied upon the interaction of transplanted normal MECs with non-mammary cells within the mammary fat-pads of recipient mice that had their endogenous epithelium removed. Here, we tested whether acellular mammary extracellular matrix (mECM) preparations are sufficient to direct differentiation of testicular-derived cells and ESCs to form functional mammary epithelial trees in vivo. We found that mECMs isolated from adult mice and rats were sufficient to redirect testicular derived …

16 Year Old Baseball Pitcher Presenting With Gradual Worsening Of Posterolateral Right Elbow Pain And Negative Mri Findings, Nithin Natwa, Reema Sheth, Nisha Sheth

Research Day

Background: Elbow pain is a common presenting symptom in repetitive motion performing athletes. Due to the popular use of prolonged conservative therapy in elbow pain, and the importance of early surgical intervention in Elbow Synovial Fold Syndrome, proper and prompt diagnosis is essential. In our case report, a 16 year old male right hand-dominant baseball pitcher presents with gradual onset of posterolateral right elbow pain over 4 months. Purpose: This study helps reflect the correct timeline in imaging along with the appropriate duration of conservative management. After reviewing this study the reader will be better able to differentiate between Lateral …

Pheochromocytoma With Ivc Invasion: Case Report & Systematic Review Of Literature, Jennifer Kim Bs, Ms2, Gitonga Munene M.D., David Schutter Md, Pgy3

Research Day

Surgical management and outcome of pheochromocytoma with invasion of the inferior vena cava (IVC) has not been thoroughly reported or widely available in the literature. As determining the malignancy of pheochromocytoma has yet to be clearly defined and the experience of surgical resection of this condition is underrepresented, we include a case report and a systematic literature review on this condition. A literature search in PubMed was performed based on a recent review article by Kassahun et al. (2016). The search yielded 13 case reports between 1988 and 2014 from which data was extracted based on the following variables: patient’s …

Gallbladder Duplication: Case Report Of A Rare Congenital Anomaly Treated By Single-Incision Laparoscopic Cholecystectomy In A Pediatric Patient, Jairo Espinosa M.D., Peter White, Michael Leinwand M.D.

Research Day

Introduction: Gallbladder duplication is a rare congenital anomaly. Preoperative diagnosis is essential for prevention of intra operative complications. Based on our review of the literature, this is the first description of gallbladder duplication treated with single-incision laparoscopic surgery (SILS) in a pediatric patient.

Case Presentation: A 14 year-old girl presented to the pediatric surgery clinic with a 4-month history of right upper quadrant abdominal pain, nausea, and low- grade fevers. Preoperative imaging revealed gallbladder duplication. The single incision laparoscopic technique was employed. Intra operative ndings included two gallbladders that appeared to share a common wall. There were two parallel cystic …

Acquired Craniosynostosis In A Patient With Iatrogenic Vitamin D Intoxication, Wesley Eichorn, Kristi Vanderkolk Md

Research Day

Introduction: Craniosynostosis, which refers to premature fusion of cranial sutures, is an uncommon diagnosis in the pediatric patient, occurring with an incidence of approximately 1 in 2,000 individuals. It is most often associated with X-Linked hypophosphatemic rickets. The implications of craniosynostosis, especially with a delayed diagnosis, are severe. Case Report: MJ is an African American male born at term via cesarean section with an unremarkable immediate postnatal period. He was diagnosed with rickets at the age of 7 months but treatment was not immediately initiated. He presented again at age 9 months with an upper respiratory infection and failure to …

Infection-Associated Mycobacterium Fortuitum Infection, Dennis T. Huang, Larry Lutwick

Research Day

Introduction: Mycobacterial species are unusual causes of skin and soft tissue infections and can be difficult to diagnose in the absence of consideration as they often require specific culture media and longer incubation times. We report a Mycobacterium fortuitum subcutaneous abscess in a diabetic related to medication injection that was initially diagnosed without specialized media or prolonged incubation times. Case Report: A 48 year old diabetic female developed a progressive subcutaneous swelling in the tissues of the right lower abdominal wall where she had been injecting liraglutide. Because of continued enlargement "to almost egg size" with pain, she was empirically …

Mechanical Loading As Potential Treatment For Wnt Inhibitor Induced Bone Loss, Juraj Zahatnansky Md, Daniel Dick, Gabrielle Foxa, Robert Baker, Bart Williams Phd

Research Day

The Wnt signaling pathway has been shown to play a role in bone homeostasis and carcinogenesis. On the one hand, a decrease in signaling has been associated with a decrease in bone mass, on the other, an increase in signaling with cancer development. LGK974 is a Wnt signaling inhibitor currently being investigated as a potential cancer therapeutic agent. This molecule inhibits Porcupine, a transmembrane protein necessary for Wnt ligand secretion. In light of the above and based on our preliminary data, treatment with LGK974 leads to bone mass loss. Our investigation aims to address whether such bone loss can be …

Cryptococcal Empyema: A Rare Manifestation Of Disease, Mohamed Mortagy, Larry Lutwick, Stephen Breisach

Research Day

Introduction: Cryptococcus neoformans is a pathogenic yeast that is generally acquired by man from the environment via the respiratory route. Despite this route of acquisition, overt pulmonary infection is uncommonly diagnosed and the disease is usually manifest as a subacute meningitis which is mostly manifest in individuals who are celluarly immunoincompetent such as those on cancer chemotherapy, receiving anti-solid organ rejection medications and those with HIV/AIDS. Infection of the pleural space with C. neoformans is quite uncommon. We report a non-immunosuppressed man who was found to have infection of the pleural in the wake of bacterial empyema who was successfully …

Mycobacterial Disease Overlooked In A Frail Diabetic Male Treated For Pneumonia, Aydin Tavakoli Md Msc, Glenn V. Dregansky Do

Research Day

Mycobacterial disease has been characterized to cause human illness since the 1950’s but practitioners whom address pulmonary disease can overlook its insidious presentation. This case report documents the presentation of a mycobacterial illness treated as a severe pneumonia. This is the case of a critically ill 43-year-old male, with poorly treated diabetes who presented with severe, long-standing respiratory distress in DKA. He had a history of weight loss, night sweats, decreased oral intake, and weakness for about a month. He was treated for euglycemia and his pulmonary disease was characterized as a bacterial pneumonia. Common pathogens were ruled out in …

Mixed Goblet Cell Carcinoid-Adenocarcinoma: A Case Series, Jairo Espinosa M.D., Timothy Truong, Julia Miladore M.D., John T. Collins, Saad Shebrain M.D., Gitonga Munene M.D.

Research Day

INTRODUCTION: Mixed goblet cell carcinoid-adenocarcinoma (GCC) tumors are a group of rare heterogenous neoplasms of the appendix accounting for < 5% of all primary appendiceal tumors. They are characterized as an intermediate between classic carcinoid tumors and appendiceal adenocarcinomas, exhibiting both neuroendocrine and glandular/mucinous morphology that most commonly presents in Caucasian females in the fifth and sixth decades. We present three cases of mixed GCC presenting as acute appendicitis. CASE PRESENTATION: Case #1 A 65-year-old male presented with RLQ pain, nausea, emesis, and leukocytosis. CT of the abdomen revealed perforated appendicitis. The patient underwent a laparoscopic appendectomy. Pathology revealed a high-grade adenocarcinoma ex goblet cell carcinoid, signet ring type extending through the muscularis propria into the mesoappendix measuring >3cm. The patient subsequently underwent a colonoscopy that revealed diverticulosis, but was otherwise normal. Patient then underwent a right hemicolectomy and partial omentectomy. Pathology revealed normal ileal, omental, and colonic tissue without evidence of carcinoma. 0/12 nodes were positive. Case #2 A 49-year-old male presented with periumbilical pain, nausea, emesis, and leukocytosis. CT of the abdomen revealed appendicitis. The patient underwent a laparoscopic appendectomy. Pathology revealed a high-grade, poorly differentiated, adenocarcinoma ex goblet cell carcinoid invading through the muscularis propria into …

Challenges In The Diagnosis And Management Of Pediatric Pulmonary Tuberculosis In Madagascar, Emily Cordes, Richard Roach

Research Day

Introduction: Tuberculosis (TB) remains an important cause of morbidity and mortality in Madagascar. According to the World Health Organization (WHO), in 2015, the estimated incidence of TB was 57,000 and 11,000 of those cases were of patients less than 14 years old. Of the reported cases, 89% were bacteriologically confirmed. However, it is well established that bacteriologic confirmation of TB in children is especially difficult. Therefore, the incidence of TB in the pediatric population in Madagascar, and likely worldwide, is under estimated. We report a case of a 4 year old male that illustrates the challenges in diagnosis and management …

Antegrade Endosteal Fibular Strut Augmentation For Periprosthetic Femur Fracture Above Stemmed Total Knee Arthroplasty, Tyler Snoap, Jason Roberts, Matthew Jaykel

Research Day

Abstract Title: ANTEGRADE ENDOSTEAL FIBULAR STRUT AUGMENTATION FOR PERIPROSTHETIC FEMUR FRACTURE ABOVE STEMMED TOTAL KNEE ARTHROPLASTY Abstract ID: 245 Abstract Category: Clinical Research Introduction: 
The management of peri-prosthetics fracture around total knee replacements is technically challenging. The options for operative fixation become more limited if the femoral component is stemmed, which often is the case after revision arthroplasty procedures. The goals of surgery for peri-prosthetic fractures above knee replacements are to provide a rigid construct to promote healing, allow immediate knee range of motion, and allow weight bearing during the healing process. 
Purpose: 
The purpose of this study is to …

Surviving As A Cancer Survivor: A Case Report Of Radiation-Induced Autonomic Dysfunction, Daphne Sy, Mark Schauer

Research Day

While radiation and chemotherapy have achieved high rates of cure for Hodgkin lymphoma, the medical community is only now starting to characterize the long-term effects of treatment on these young cancer survivors, many decades later. Mantle radiation has been implicated in significantly increased cardiovascular risks, pulmonary fibrosis, other cancers, and thyroid disease over the patient’s lifetime. However, new syndromes are still being discovered within this population as they age. The purpose of this case study was to consider the unique health issues of cancer survivors, and how their treatment history should prompt us to broaden our differentials. Our patient presented …

Improving Productivity Through Scheduling At The Wmed Family Medicine Residency Clinic, Alex Witte Md, Susan Jevert-Eichorn, Alison Radigan Md, Larry Mann Do, Jamie Mccartney Md, Aisha Shakoor Md

Research Day

INTRODUCTION: The Accreditation Council for Graduate Medical Education (ACGME) requires every family medicine residency program to have a practice site that supports, “continuous, comprehensive, convenient, accessible, and coordinated patient care”. The WMed Family Medicine Resident Clinic (Team Oakland), located within the Family Health Center (FHC) – Paterson location, has long been plagued by scheduling difficulties, as evidenced by high no-show rates, empty appointment slots, and frequent cancellations threatening the ability of our residents to achieve the required number of outpatient visits mandated by the Family Medicine Residency Review Committee (RRC) and the requirement for continuity from the ACGME. We believe …

Social Determinants - Impacting Or Causing Disparities In Patient Care?, Shaena Faye Freeman Md, Kristi Vanderkolk Md

Research Day

Health disparities secondary to social factors including socioeconomic status, race, gender and ethnicity are well known to the health community and are a troubling issue in the United States. Social determinants are defined by the WHO as the structural “conditions people are born, live, grow, work and age in…determined by wealth distribution and available resources…that are mostly responsible for health inequalities.” We present here the case of TL, a 49 year old African American female who presented to the emergency department three times with atypical coronary disease symptoms in the setting of recent NSTEMI with subsequent 3 vessel CABG. At …

Widespread Tau Seeding Activity At Early Braak Stages, Jennifer L. Furman, Jaime Vaquer-Alicea, Charles L. White, Nigel J. Cairns, Peter T. Nelson, Marc I. Diamond

Pathology and Laboratory Medicine Faculty Publications

Transcellular propagation of tau aggregates may underlie the progression of pathology in Alzheimer's disease (AD) and other tauopathies. Braak staging (B1, B2, B3) is based on phospho-tau accumulation within connected brain regions: entorhinal cortex (B1); hippocampus/limbic system (B2); and frontal and parietal lobes (B3). We previously developed a specific and sensitive assay that uses flow cytometry to quantify tissue seeding activity based on fluorescence resonance energy transfer (FRET) in cells that stably express tau reporter proteins. In a tauopathy mouse model, we have detected seeding activity far in advance of histopathological changes. It remains unknown whether individuals with AD also …

Prebiotics And Inflammatory Bowel Disease, Heather Rasmussen, Bruce R. Hamaker

Department of Nutrition and Health Sciences: Faculty Publications

Inflammatory bowel disease risk factors include poor diet, and corresponding low intake of dietary fiber, specifically prebiotics, which is fermented by the gut microbiota. Dietary fibers, many of which are potential prebiotics, have hundreds to thousands of unique chemical structures that may promote bacteria or bacterial groups to provide beneficial health effects. In vitro and in vivo animal models provide some support for the use of prebiotics for inflammatory bowel disease through inflammation reduction. Studies using prebiotics in patients with inflammatory bowel disease are limited and focus on only a select few prebiotic substances.

Keywords: Inflammatory bowel disease, Ulcerative colitis, …

Readiness For Antimicrobial Resistance (Amr) Surveillance In Pakistan; A Model For Laboratory Strengthening, Dania Khalid Saeed, Rumina Hasan, Mahwish Naim, Afia Zafar, Erum Khan, Kauser Jabeen, Seema Irfan, Imran Ahmed, Mohammad Zeeshan, Zabin Wajidali, Joveria Farooqi, Sadia Shakoor, Abdul Chagla, Jason Roy

Department of Pathology and Laboratory Medicine

Background: Limited capacity of laboratories for antimicrobial susceptibility testing (AST) presents a critical diagnostic bottleneck in resource limited countries. This paper aims to identify such gaps and to explore whether laboratory networks could contribute towards improving AST in low resource settings. Methods: A self-assessment tool to assess antimicrobial susceptibility testing capacity was administered as a pre-workshop activity to participants from 30 microbiology laboratories in 3 cities in Pakistan. Data from public and private laboratories was analyzed and capacity of each scored in percentage terms. Laboratories from Karachi were invited to join a support network. A cohort of five laboratories that …

Anti-Proliferative Role Of Recombinant Lethal Toxin Of Bacillus Anthracis On Primary Mammary Ductal Carcinoma Cells Revealing Its Therapeutic Potential, Rekha Khandia, Bramhadev Pattnaik, Katherikamem Rajukumar, Atul Pateriya, Sandeep Bhatia, Harshad Murugkar, Anil Prakash, Hare Krishna Pradhan, Kildeep Dhama, Ashol Munjal, Sunil K. Joshi

Bioelectrics Publications

Bacillus anthracis secretes three secretary proteins; lethal factor (LF), protective antigen (PA) and edema factor (EF). The LF has ability to check proliferation of mammary tumors, chiefly depending on mitogen activated protein kinase (MAPK) signaling pathway. Evaluation of therapeutic potential of recombinant LF (rLF), recombinant PA (rPA) and lethal toxin (rLF + rPA = LeTx) on the primary mammary ductal carcinoma cells revealed significant (p < 0.01) reduction in proliferation of tumor cells with mean inhibition indices of 28.0 ±1.37% and 19.6 ± 1.47% respectively. However, treatment with rPA alone had no significant anti-proliferative effect as evident by low mean inhibition index of 3.4 ± 3.87%. The higher inhibition index observed for rLF alone as compared to LeTx is contrary to the existing knowledge on LF, which explains the requirement of PA dependent endocytosis for its enzymatic activity. Therefore, the plausible existence of PA independent mode of action of LF including direct receptor mediated endocytosis or modulation of signal transduction cascade via unknown means is hypothesized. In silico protein docking analysis of other cellular receptors for any plausibility to play the role of receptor for LF revealed c-Met receptor showing strongest affinity for LF (H bond = 19; Free energy = …

Peripheral Huntingtin Silencing Does Not Ameliorate Central Signs Of Disease In The B6.Httq111/+ Mouse Model Of Huntington's Disease., Sydney R Coffey, Robert M Bragg, Shawn Minnig, Seth A Ament, Jeffrey P Cantle, Anne Glickenhaus, Daniel Shelnut, José M Carrillo, Dominic D Shuttleworth, Julie-Anne Rodier, Kimihiro Noguchi, C Frank Bennett, Nathan D Price, Holly B Kordasiewicz, Jeffrey B Carroll

Articles, Abstracts, and Reports

Huntington's disease (HD) is an autosomal dominant neurodegenerative disease whose predominant neuropathological signature is the selective loss of medium spiny neurons in the striatum. Despite this selective neuropathology, the mutant protein (huntingtin) is found in virtually every cell so far studied, and, consequently, phenotypes are observed in a wide range of organ systems both inside and outside the central nervous system. We, and others, have suggested that peripheral dysfunction could contribute to the rate of progression of striatal phenotypes of HD. To test this hypothesis, we lowered levels of huntingtin by treating mice with antisense oligonucleotides (ASOs) targeting the murine …