Medicine and Health Sciences Commons^™

Assessing Adequacy: A Meta-Analysis Of Rapid Onsite Evaluation Of Thyroid Nodules, Peter P. Issa, Christina Mccarthy, Mohammad Hussein, Aaron L. Albuck, Essam Emad, Mohamed Shama, Krzysztof Moroz, Eman Toraih, Emad Kandil

School of Medicine Faculty Publications

Introduction: Fine-needle aspiration (FNA) is the standard form of preoperative evaluation of thyroid nodule cytological status. A significant number FNAs are classified as inadequate for interpretation, requiring a repeat FNA which is potentially avoidable, costly, and delays treatment. To address these concerns and maximize first-time FNA adequacy, rapid onsite evaluation (ROSE) of FNA specimens was introduced. Our study aims to determine the impact of ROSE on FNA adequacy. Methods: PubMed, Embase, and Web of Science were searched for primary articles assessing the adequacy of ROSE in thyroid nodules. Results: A total of 17 studies were included for a total of …

The Role Of Molecular Thyroseq V3 Testing For Diagnosis And Management Of Indeterminate Thyroid Nodules., Ruth Delahunty

International Undergraduate Journal of Health Sciences

Worldwide, thyroid cancer is the 8^th most common malignancy (3^rd most common in women) and in recent years, there has been increased incidence of thyroid cancer worldwide. There is currently said to be a of thyroid nodules as of 2022. When it comes to the management of indeterminate thyroid nodules, clinical decision making can be challenging.

Thyroseq V3 testing may be used to determine the percentage probability of a thyroid nodule of being either malignant or benign, through a complex algorithm with next generation sequencing techniques, currently testing is done in the University of Pittsburgh and therefore is …

Labrad : Vol 48, Issue 1 - July 2023, Aga Khan University Hospital, Karachi

LABRAD

• Editorial
• Articles
• Toxicology In Public Health: Mitigating Risk, Fostering Well-Being
• Predictive And Prognostic Biomarkers in Histopathology
• Cancer Registry and Public Health Surveillance - Role of Pathologists
• Diagnosis of Celiac Disease DQA1*02,05; DQB1*02,03:02 (DQ2&DQ8) in patients
• Magnifying The Clinical Value of Expert Review and Reassessment
• Urine Cytology: A Screening and Surveillance Test
• An Overview of Convalescent Plasma for The Treatment of COVID-19
• Role of Imaging in Public Health Care
• Microsatellite Instability (MSI) Testing
• MRI Liver with Hepatocyte-Specific Contrast Agent
• Basics and Role of Cytopathology
• Bone Tumors: From Timely Diagnosis to Improved Patient Outcome
• Differentiating Between Dengue Fever and Malaria Using The …

Immunohistochemistry For The Proliferation Markers Ki67 And Phh3 In Cell Block Material Of Basaloid Salivary Gland Neoplasms Is Predictive Of Malignancy, Robert Post, Zach Breslin, Yanki Yarman, Stacey Gargano

Department of Pathology, Anatomy, and Cell Biology Posters

Background: Basaloid salivary gland neoplasms (BSGNs) are notoriously difficult to classify in fine needle aspiration (FNA) specimens due to the morphologic overlap shown by the various benign and malignant entities in this category1,2,3. Adenoid cystic carcinoma (AdCC) represents a particular diagnostic challenge, as it typically shows low grade cytologic features despite its aggressive clinical behavior and need for more extensive surgery4. We examined whether the proliferation markers Ki67 and PHH3 could help predict malignancy in BSGNs, thus improving diagnostic accuracy and optimizing patient care.

How Irish Medical Scientists Can Assist In The Improved Diagnosis Of The Disease Infectious Mononucleosis, Patrick Naughton

ORBioM (Open Research BioSciences Meeting)

Background:

The eponymously named Epstein-Barr Virus (EBV) or human herpesvirus 4 (HHV-4) is the sole causative agent of the acute illness in humans described either as infectious mononucleosis (IM), or glandular fever. IM, when not clinically silent, can present in patients with at least two of the classic triad of symptoms of fever, pharyngitis, and lymphadenopathy. Challenges for the clinician arise when atypical cases present. Early, accurate and informed laboratory test results are vital for diagnosis, appropriate treatment, and patient management. A key challenge for the practitioner, particularly in cases where the illness can present atypically, is distinguishing bacterial tonsillitis …

Diagnostic Imaging And Hematological And Cytological Analyses Play A Vital Role In Clinical Investigation And Selection Of Therapeutic Approaches In A Polo Pony With Septic Olecranon Bursitis, Rungrueang Yodsheewan, Ravisara Limsripan, Metha Chanda

The Thai Journal of Veterinary Medicine

A 19-year-old gelding polo pony was presented with a prominent protuberance at the tip of the right elbow and five days later, developed a marked swelling on the entire right foreleg with a high fever. Ultrasonography, performed on the caudal elbow region, demonstrated heterogeneous echogenic materials encapsulated in the fibrous capsule. The initial hematological analysis revealed anemia and a normal white blood count (WBC). Hyperbilirubinemia was detected biochemically. Pale yellow/turbid fluid was aspirated from the protuberance area, which showed septic exudate characteristics and contained Streptococcus spp. The pony was diagnosed with septic olecranon bursitis associated with streptococcal infection. The fluid-filled …

Diagnosing Vitreoretinal Lymphomas—An Analysis Of The Sensitivity Of Existing Tools, Anahita Sehgal, Jose S. Pulido, Arman Mashayekhi, Tatyana Milman, Gabor Gy Deák

Wills Eye Hospital Papers

Vitreoretinal Lymphoma (VRL) is a rare ocular pathology that is notorious for mimicking chronic uveitis, which is a seemingly benign condition in comparison. The most common form of VRL is the diffuse large B-cell type, and there has been a high mortality rate. This dismal prognosis can be improved significantly if the disease is diagnosed early, but until now there is no consensus on an appropriate diagnostic algorithm. We conducted a retrospective search of PubMed Central® and analyzed results from thirty-three studies that were published between 2011–2021. The chosen studies incorporated some popular testing tools for VRL, and our analyses …

Development And Validation Of A Raman Spectroscopic Classification Model For Cervical Intraepithelial Neoplasia (Cin), Damien Traynor, Shiyamala Duraipandian, Ramya Bhatia, Kate Cuschieri, Prerna Tewari, Padraig Kearney, Tom D'Arcy, John J. O'Leary, Cara M. Martin, Fiona Lyng

Articles

The mortality associated with cervical cancer can be reduced if detected at the precancer stage, but current methods are limited in terms of subjectivity, cost and time. Optical spectroscopic methods such as Raman spectroscopy can provide a rapid, label-free and nondestructive measurement of the biochemical fingerprint of a cell, tissue or biofluid. Previous studies have shown the potential of Raman spectroscopy for cervical cancer diagnosis, but most were pilot studies with small sample sizes. The aim of this study is to show the clinical utility of Raman spectroscopy for identifying cervical precancer in a large sample set with validation in …

Novel Fusion Ktn1-Prkd1 In Cribriform Adenocarcinoma Of Salivary Glands Located In The Parotid Gland: Case Report Including Cytologic Findings, Treeva K. Jassim, T. Sheng, Shulin Zhang, Sainan Wei, Susanne M. Arnold, Alexandra E. Kejner, Therese J. Bocklage, Julie C. Dueber

Pathology and Laboratory Medicine Faculty Publications

Background
Cribriform adenocarcinoma of salivary glands (CASG) is a rare, predominantly minor salivary gland tumor first described in 1999. Because the tumor shares morphologic and molecular features with polymorphous adenocarcinoma (PAC), in 2017, the World Health Organization (WHO) included CASG within the spectrum of PAC. Almost 75% of CASG harbor molecular alterations in the PRKD (Protein kinase D) gene family, and some cases show ARID1A (AT-rich interaction domain 1A)-PRKD1 or DDX3X (DEAD-Box Helicase 3 X-Linked)-PRKD1 fusions.

Case presentation
A 39-year-old man presented with headache and painless right cheek mass of two years duration. Imaging showed a well-circumscribed, …

Depolarization-Initiated Endogenous Cannabinoid Release And Underlying Retrograde Neurotransmission In Interneurons Of Amygdala, Sodikdjon A. Kodirov, Kathrin Bonni, Michael Wehrmeister, Beat Lutz

Health & Biomedical Sciences Faculty Publications and Presentations

The depolarization is also important for the short-term synaptic plasticity, known as depolarization-induced suppression of excitation (DSE). The two major types of neurons and their synapses in the lateral nucleus of amygdala (LA) are prone to plasticity. However, DSE in interneurons has not been reported in amygdala in general and in LA in particular. Therefore, we conducted the patch-clamp experiments with LA interneurons. These neurons were identified by lack of adaptation in firing rate of action potentials. In this study, we show for the first time a transient suppression of neurotransmission at synapses both within the local network and between …

Role Of Fine Needle Aspiration Cytology In The Diagnosis Of Parotid Gland Tumors: Analysis Of 193 Cases, Rahim Dhanani, Haissan Iftikhar, Mohammad Sohail Awan, Nida Zahid, Sehrish Nizar Ali Momin

Section of Otolaryngology, Head & Neck Surgery

Introduction: Parotid gland tumors include a wide variety of inflammatory and neoplastic diseases. The majority of these tumors are benign (80%), which usually require superficial parotidectomy, while the incidence of malignant tumors is lower (20%), requiring more radical surgery with or without neck dissection. The diagnosis cannot be established on the basis of clinical history and simple physical examination and requires complementary diagnostic methods. Fine needle aspiration cytology (FNAC) guided by ultrasound is a widely used diagnostic tool to evaluate parotid swellings.
Objective: To determine the sensitivity, specificity, positive and negative predictive values and diagnostic accuracy of FNAC in the …

Randomised Placebo-Controlled Cross-Over Study Examining The Role Of Anamorelin In Mesothelioma (The Anthem Study): Rationale And Protocol, Siao Nge Hoon, Katrina Fyfe, Carolyn J. Peddle-Mcintyre, Samantha Bowyer, Felicity Hawkins, Emily Jeffery, Hui Jun Chih, Jenette Creaney, Anna Nowak, Fraser Brims

Research outputs 2014 to 2021

Introduction Cachexia is common in malignant mesothelioma (MM); half of patients have malnutrition and low skeletal muscle mass. Malnourished patients have worse quality of life (QoL). Weight loss is strongly associated with poor survival. Anamorelin is an oral ghrelin receptor agonist that improves appetite, body weight and QoL in advanced cancer. The aim of this study is to examine the efficacy of anamorelin in improving appendicular skeletal muscle mass (ASM) and patient-reported outcomes in patients with MM with cachexia. Methods and analysis A single-centre, phase II, randomised, placebo-controlled cross-over pilot study with 28-day treatment periods and 3-day washout. Forty patients …

The Potential Of Biobanked Liquid Based Cytology Samples For Cervical Cancer Screening Using Raman Spectroscopy., D. Traynor, S. Duraipandian, R. Bhatia, K. Cuschieri, C. M. Martin, J. J. O'Leary, Fiona Lyng

Articles

Patient samples are unique and often irreplaceable. This allows biobanks to be a valuable source of material. The aim of this study was to assess the ability of Raman spectroscopy to screen for histologically confirmed cases of Cervical Intraepithelial neoplasia (CIN) using biobanked liquid based cytology (LBC) samples. Two temperatures for long term storage were assessed; 80°C and -25°C. The utility of Raman spectroscopy for the detection of CIN was compared for fresh LBC samples and biobanked LBC samples. Two groups of samples were used for the study with one group associated with disease (CIN 3) and the other associated …

Recent Advances In The Vibrational Spectroscopic Diagnosis Of Non-Small Cell Lung Cancer, Declan O'Dea, Fiona Lyng, Siobhan Nicholson, Finbar O'Connell, Aoife Maguire, Alison Malkin

Articles

Lung cancer is the leading cause of cancer deaths worldwide accounting for 1.69 million deaths in 2015. Studies have indicated a 5 year survival rate of 8%–15% in western countries, although a survival rate as low as 1% has been demonstrated for late stage diagnosis. With the advent of targeted therapies, it is imperative to accurately differentiate non-small cell lung cancer (NSCLC) subtypes in order to ensure efficacy of treatment for patients. Immunohistochemistry and molecular techniques for the diagnosis of NSCLC are increasingly part of the diagnostic algorithm and clinical work-up of lung cancer patients, however due to the limitation …

Adaptation Mechanism And Tolerance Of Rhodopseudomonas Palustris Psb-S Under Pyrazosulfuron-Ethyl Stress, Xiang-Wen Luo, De-Yang Zhang, Teng-Hui Zhu, Xuguo Zhou, Jing Peng, Song-Bai Zhang, Yong Liu

Entomology Faculty Publications

Background: Pyrazosulfuron-ethyl is a long lasting herbicide in the agro-ecosystem and its residue is toxic to crops and other non-target organisms. A better understanding of molecular basis in pyrazosulfuron-ethyl tolerant organisms will shed light on the adaptive mechanisms to this herbicide.

Results: Pyrazosulfuron-ethyl inhibited biomass production in Rhodopseudomonas palustris PSB-S, altered cell morphology, suppressed flagella formation, and reduced pigment biosynthesis through significant suppression of carotenoids biosynthesis. A total of 1127 protein spots were detected in the two-dimensional gel electrophoresis. Among them, 72 spots representing 56 different proteins were found to be differently expressed using MALDI-TOF/TOF-MS, including 26 up- and 30 …

Improved Removal Of Blood Contamination From Thinprep Cervical Cytology Camples For Raman Spectroscopic Analysis, Damien Traynor, Shiyamala Duraipandian, C.Ara M. Martin, John J. O'Leary, Fiona Lyng

Articles

There is an unmet need for methods to help in the early detection of cervical precancer. Optical spectroscopy-based techniques, such as Raman spectroscopy, have shown great potential for diagnosis of different cancers, including cervical cancer. However, relatively few studies have been carried out on liquid-based cytology (LBC) pap test specimens and confounding factors, such as blood contamination, have been identified. Previous work reported a method to remove blood contamination before Raman spectroscopy by pretreatment of the slides with hydrogen peroxide. The aim of the present study was to extend this work to excessively bloody samples to see if these could …

A Study Of Hormonal Effects In Cervical Smear Samples Using Raman Spectroscopy, D. Traynor, P. Kearney, I. Ramos, C. M. Martin, J. J. O'Leary, Fiona Lyng

Articles

Raman spectroscopy is a powerful tool that has the potential to be used as a screening method for cervical cancer. It is a label-free, low-cost method providing a biochemical fingerprint of a given sample. The objective of this study was to address patient-to-patient variability contributed by hormonal effects due to the menstrual cycle, the use of hormone-based contraceptives (HC) and the onset of menopause, and to determine if these changes would affect the ability to successfully identify dyskaryotic cells. Raman spectra were recorded from unstained ThinPrep cervical samples (45 cytology negative and 15 high-grade dyskaryosis (high-grade squamous intraepithelial lesion, HSIL) …

Assessment Of Tumor-Induced Pain And C-Reactive Protein Levels In Dogs With Caninetransmissible Venereal Tumors, Waqas Ahmad, Muti-Ur- Rehman, Aftab Ahmad Anjum, Gulbeena Saleem, Ubaid Ur Rehman Zia, Muhammad Azeem, Fahad Akram

Turkish Journal of Veterinary & Animal Sciences

The aim of this study was to determine the impact of tumor volume on generalized behavior, pain perception, and serum C-reactive protein (CRP) in dogs with canine transmissible venereal tumors (CTVTs). Pain scoring was performed using the Glasgow Composite Measure Pain Scale Short-Form. Cytomorphology of the tumors was studied through fine-needle aspiration and histopathology. Molecular identification of CTVTs was carried out using PCR assays based on LINE-1/c-myc. Hematological profiles including complete blood count and CRP were analyzed using an automatic hematology analyzer and immunoturbidimetric assays, respectively. Chi-square and regression analysis statistics were used for data analysis. Results of the study …

Increased Micronucleus Count Predicts Malignant Behavior In Pleural Effusion Fluid, Tuba Di̇lay Kökenek Ünal, İpek Çoban

Turkish Journal of Medical Sciences

Background/aim: Micronucleus (MN) frequency is used as a biomarker of chromosomal damage, genome instability, and cancer risk. e aim of this study was to evaluate the diagnostic usefulness of MN frequency to di erentiate between malignant and benign pleural e usion samples. Materials and methods: Retrospectively, 78 pleural uid cytology samples (including 20 cases of benign reactive mesothelial cells, 22 cases of suspicious cytology, and 36 cases of malignant cytology) were examined. e number of micronucleated cells in 1000 well- preserved cells was counted. Statistical tests were performed to compare the study groups. Recover operating characteristics (ROC) curve analysis was …

Hpv Types And E6/E7 Mrna Expression In Cervical Samples From Turkish Women With Abnormal Cytology In Ankara, Turkey, İpek Tüney, Ayli̇n Altay, Koray Ergünay, Sevgen Çeli̇k Önder, Alp Usubütün, Mehmet Coşkun Salman, Gülendam Bozdayi, Erdem Karabulut, Osman Seli̇m Badur, Kunter Yüce, Ahmet Pinar

Turkish Journal of Medical Sciences

Background/aim: Human papillomaviruses have been established as a risk factor for invasive carcinoma of the uterine cervix. HPV E6/E7 oncogene expression has recently emerged as a promising biomarker to determine the risk for progression to high-grade cervical lesions. The aim of this study was to evaluate HPV mRNA and DNA detection in samples with abnormal cytology. Materials and methods: Cervical specimens were obtained at the Department of Obstetrics and Gynecology via cervical brushes during January-October 2011. Liquid-based cytology slides were evaluated according to the 2001 Bethesda System. Cytology specimens from a total of 81 women with abnormal cytology were included. …

Effect Of The Time Of Day And Queue Position In The Endoscopic Schedule On The Performance Characteristics Of Endoscopic Ultrasound-Guided Fine-Needle Aspiration For Diagnosing Pancreatic Malignancies., Jason Korenblit, Danielle M Tholey, Joanna Tolin, David Loren, Thomas Kowalski, Douglas G. Adler, Julie Davolos, Ali A. Siddiqui

Division of Gastroenterology and Hepatology Faculty Papers

BACKGROUND AND OBJECTIVES: Recent reports have indicated that the time of day may impact the detection rate of abnormal cytology on gynecologic cytology samples. The aim of this study was to determine if procedure time or queue position affected the performance characteristics of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) for diagnosing solid pancreatic malignancies.

PATIENTS AND METHODS: We conducted a retrospective study evaluating patients with solid pancreatic lesions in whom EUS-FNA was performed. Three timing variables were evaluated as surrogate markers for endoscopist fatigue: Procedure start times, morning versus afternoon procedures, and endoscopy queue position. Statistical analyses were performed to determine …

Methodologies And Considerations For Bladder Cancer Detection With Raman Based Urine Cytology, Laura T. Kerr, Thérése M. Lynn, Ivor M. Cullen, Padraig J. Daly, Nigam Shah, Shirley O'Dea, Alison Malkin, Bryan M. Hennelly

Articles

Bladder cancer has the highest recurrence rate of any cancer. The American Urological Association recommends cystoscopic surveillance every 3–6 months for 3 years, and at least once a year thereafter, particularly for high-risk patients; however, cystoscopy is invasive, expensive, and is not without insignificant morbidity for the patient. Urine cytology is often used as an adjunct to cystoscopy; however, it has a low sensitivity in detecting low grade bladder cancers. Recent studies have investigated the application of Raman micro-spectroscopy for the detection of bladder cancer via urine cytology, and it has been demonstrated to significantly improve the diagnostic sensitivity of …

New And Contemporary Markers Of Prognosis In Nonmuscle Invasive Urothelial Cancer, Hammad Ather, Syed M Nazim

Department of Surgery

Abstract

Nonmuscle invasive (NMI) urothelial cancer (UC) is associated with varied biological potential. It is characterized by frequent recurrence and progression, which thus worsens the oncological outcome. Nearly three-quarters of NMI UCs recur within 5 years, whereas half can progress during follow-up. Progression is particularly seen in T1 and carcinoma in situ (CIS). Undoubtedly, NMI UC is one of the most expensive cancers to manage. The European Organisation for Research and Treatment of Cancer (EORTC) risk calculator is a commonly used tool for assessing the recurrence and progression potential of a newly diagnosed cancer. The parameters used in the assessment …

Endometrial Cytology As A Diagnostic Tool For Subclinical Endometritis In Beef Heifers, Carlos Moscuzza, Guadalupe Alvarez, Betiana Gutierrez, Marcelo Zurita, Marcelo Tropeano, Roberto Perna

Turkish Journal of Veterinary & Animal Sciences

The obstetric assistance of dystocia in field conditions promotes greater bacterial contamination of the uterus, causing subclinical endometritis. The aim of this study was to determine the occurrence of subclinical endometritis in beef heifers receiving professional calving assistance, and to evaluate endometrial cytology as a diagnostic technique compared to uterine biopsy. A group of 829 Angus heifers were assisted at calving. Dystocia was classified based on difficulty at assistance, which was estimated as complex or simple. At the end of the calving season, 93 dystocic heifers were reported (10.7%). The percentage of simple resolution and complex resolution was 88.2% and …

The Risk Of Tumor Cell Dissemination In Mediastinoscopy: A Cytological Study, Yasemi̇n Bi̇lgi̇n Büyükkarabacak, Ayşen Taslak Şengül, Bi̇lge Can Meydan, Burçi̇n Çeli̇k, Mehmet Gökhan Pi̇rzi̇renli̇, Selçuk Gürz, Zeynep Peli̇n Sürücü, Ahmet Başoğlu

Turkish Journal of Medical Sciences

Background/aim: Mediastinoscopy is an invasive procedure that is used in the diagnosis of mediastinal diseases and in staging lung cancer. Tumor cell seeding during mediastinoscopy along the mediastinum and the incision line is a very rare complication. This study aimed to test the safety of mediastinoscopy in terms of tumor seeding by cytological evaluation of mediastinal lavage samples taken before and after biopsy. Materials and methods: The patients who underwent mediastinoscopy in our hospital between 2011 and 2014 were studied prospectively. Seventy-three patients with a diagnosis of lung or mediastinal malignancy were included in the study. All patients underwent classical …

Syndecan 4 Is Required For Endothelial Alignment In Flow And Atheroprotective Signaling, Nicolas Baeyens, Mary Jo Mulligan-Kehoe, Federico Corti, David D. Simon, Tyler D. Ross, John M. Rhodes, Thomas Z. Wang

Dartmouth Scholarship

Atherosclerotic plaque localization correlates with regions of disturbed flow in which endothelial cells (ECs) align poorly, whereas sustained laminar flow correlates with cell alignment in the direction of flow and resistance to atherosclerosis. We now report that in hypercholesterolemic mice, deletion of syndecan 4 (S4−/−) drastically increased atherosclerotic plaque burden with the appearance of plaque in normally resistant locations. Strikingly, ECs from the thoracic aortas of S4−/− mice were poorly aligned in the direction of the flow. Depletion of S4 in human umbilical vein endothelial cells (HUVECs) using shRNA also inhibited flow-induced alignment in vitro, which was rescued by re-expression …

Biomarkers Of Alzheimer's Disease Risk In Peripheral Tissues; Focus On Buccal Cells, Maxime François, Wayne Leifert, Ralph Martins, Philip Thomas, Michael Fenech

Research outputs 2014 to 2021

Alzheimer's disease (AD) is a progressive degenerative disorder of the brain and is the most common form of dementia. To-date no simple, inexpensive and minimally invasive procedure is available to confirm with certainty the early diagnosis of AD prior to the manifestations of symptoms characteristic of the disease. Therefore, if population screening of individuals is to be performed, more suitable, easily accessible tissues would need to be used for a diagnostic test that would identify those who exhibit cellular pathology indicative of mild cognitive impairment (MCI) and AD risk so that they can be prioritized for primary prevention. This need …

Bioengineered Lysozyme Reduces Bacterial Burden And Inflammation In A Murine Model Of Mucoid Pseudomonas Aeruginosa Lung Infection, Charlotte C. Teneback, Thomas C. Scanlon, Matthew J. Wargo, Jenna L. Bement, Karl E. Griswold, Laurie W. Leclair

Dartmouth Scholarship

The spread of drug-resistant bacterial pathogens is a growing global concern and has prompted an effort to explore potential adjuvant and alternative therapies derived from nature's repertoire of bactericidal proteins and peptides. In humans, the airway surface liquid layer is a rich source of antibiotics, and lysozyme represents one of the most abundant and effective antimicrobial components of airway secretions. Human lysozyme is active against both Gram-positive and Gram-negative bacteria, ac

Flagellar Motility Is A Key Determinant Of The Magnitude Of The Inflammasome Response To Pseudomonas Aeruginosa, Yash R. Patankar, Rustin R. Lovewell, Matthew E. Poynter, Jeevan Jyot, Barbara I. Kazmierczak, Brent Berwin

Dartmouth Scholarship

We previously demonstrated that bacterial flagellar motility is a fundamental mechanism by which host phagocytes bind and ingest bacteria. Correspondingly, loss of bacterial motility, consistently observed in clinical isolates from chronic Pseudomonas aeruginosa infections, enables bacteria to evade association and ingestion of P. aeruginosa by phagocytes both in vitro and in vivo. Since bacterial interactions with the phagocyte cell surface are required for type three secretion system-dependent NLRC4 inflammasome activation by P. aeruginosa, we hypothesized that reduced bacterial association with phagocytes due to loss of bacterial motility, independent of flagellar expression, will lead to reduced inflammasome activation. Here we report …

Engineering A Bcr-Abl–Activated Caspase For The Selective Elimination Of Leukemic Cells, Manabu Kurokawa, Takahiro Ito, Chih-Sheng Yang, Chen Zhao

Dartmouth Scholarship

Increased understanding of the precise molecular mechanisms involved in cell survival and cell death signaling pathways offers the promise of harnessing these molecules to eliminate cancer cells without damaging normal cells. Tyrosine kinase oncoproteins promote the genesis of leukemias through both increased cell proliferation and inhibition of apoptotic cell death. Although tyrosine kinase inhibitors, such as the BCR-ABL inhibitor imatinib, have demonstrated remarkable efficacy in the clinic, drug-resistant leukemias emerge in some patients because of either the acquisition of point mutations or amplification of the tyrosine kinase, resulting in a poor long-term prognosis. Here, we exploit the molecular mechanisms of …