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An Innovative Phase I Trial Design Allowing For The Identification Of Multiple Potential Maximum To Lerated Doses With Combination Therapy Of Targeted Agents, Sarina A. Piha-Paul Aug 2010

An Innovative Phase I Trial Design Allowing For The Identification Of Multiple Potential Maximum To Lerated Doses With Combination Therapy Of Targeted Agents, Sarina A. Piha-Paul

Dissertations and Theses (Open Access)

Treatment for cancer often involves combination therapies used both in medical practice and clinical trials. Korn and Simon listed three reasons for the utility of combinations: 1) biochemical synergism, 2) differential susceptibility of tumor cells to different agents, and 3) higher achievable dose intensity by exploiting non-overlapping toxicities to the host. Even if the toxicity profile of each agent of a given combination is known, the toxicity profile of the agents used in combination must be established. Thus, caution is required when designing and evaluating trials with combination therapies. Traditional clinical design is based on the consideration of a single …


The Challenge Of Head & Neck Squamous Cell Carcinoma Control In Pakistan, Syed Mohammad Asad Zaidi, Nauman Fazal Manzoor, Shabbir Akhtar Aug 2010

The Challenge Of Head & Neck Squamous Cell Carcinoma Control In Pakistan, Syed Mohammad Asad Zaidi, Nauman Fazal Manzoor, Shabbir Akhtar

Section of Otolaryngology, Head & Neck Surgery

No abstract provided.


Blastocystis Hominis And Dientamoeba Fragilis In Patients Fulfilling Irritable Bowel Syndrome Criteria., Javed Yakoob, Wasim Jafri, Mohammad Asim Beg,, Z Abbas, Shagufta Naz,, Muhammad Islam, Rustam Khan Aug 2010

Blastocystis Hominis And Dientamoeba Fragilis In Patients Fulfilling Irritable Bowel Syndrome Criteria., Javed Yakoob, Wasim Jafri, Mohammad Asim Beg,, Z Abbas, Shagufta Naz,, Muhammad Islam, Rustam Khan

Section of Gastroenterology

Studies have suggested a possible role for Blastocystis hominis and Dientamoeba fragilis in the etiology of irritable bowel syndrome (IBS). We studied the prevalence of B. hominis and D. fragilis in patients with IBS-diarrhea (IBS-D). Three hundred and thirty patients were enrolled, 171 (52%) with IBS-D and 159 (48%) were controls, respectively. Stool microscopy, culture, and polymerase chain reaction (PCR) for B. hominis and D. fragilis were done. B. hominis was positive by stool microscopy in 49% (83/171) of IBS compared to 24% (27/159) in control (p < 0.001). B. hominis culture was positive in 53% (90/171) in IBS compared to 16% (25/159) in control (p < 0.001). B. hominis PCR was positive in 44% (75/171) in IBS compared to 21% (33/159) in control (p < 0.001). D. fragilis microscopy was positive in 3.5% (6/171) in IBS-D compared to 0.6% (1/159) in control (p = 0.123). D. fragilis culture was positive in 4% (7/171) in IBS compared to 1.3% (2/159) in control (p = 0.176). D. fragilis PCR was positive in 4% (6/171) in IBS-D compared to 0% (0/159) in control (p = 0.030). B. hominis is common, while D. fragilis was less prevalent in our patients with IBS-D. B. hominis and D. fragilis culture had a better yield compared to stool microscopy and PCR.


The Perils Of The Imperfect Expectation Of The Perfect Baby., Frank A Chervenak, Laurence B Mccullough, Robert L Brent Aug 2010

The Perils Of The Imperfect Expectation Of The Perfect Baby., Frank A Chervenak, Laurence B Mccullough, Robert L Brent

Department of Pediatrics Faculty Papers

Advances in modern medicine invite the assumption that medicine can control human biology. There is a perilous logic that leads from expectations of medicine's control over reproductive biology to the expectation of having a perfect baby. This article proposes that obstetricians should take a preventive ethics approach to the care of pregnant women with expectations for a perfect baby. We use Nathaniel Hawthorne's classic short story, "The Birthmark," to illustrate the perils of the logic of control and perfection through science and then identify possible contemporary sources of the expectation of the perfect baby. We propose that the informed consent …


Expression Of Gna12 And Ifitm3, And Their Roles In Oral Carcinogenesis., Gan Chai Phei Aug 2010

Expression Of Gna12 And Ifitm3, And Their Roles In Oral Carcinogenesis., Gan Chai Phei

Student Works (2010-2019)

Oral squamous cell carcinoma (OSCC) is a major health problem worldwide. The heterogeneity of the disease is the main challenge for the improvement of current treatment modalities. Efforts in our laboratory have focused on the molecular profiling of oral cancer in order to understand the mechanisms underlying this disease. Based on the previous microarray data, Guanine nucleotide binding protein alpha-12 (GNA12) and Interferon inducible transmembrane protein 3 (IFITM3) were identified to be up-regulated in oral cancer. Objectives: This study aims to validate the expression of GNA12 and IFITM3 at the mRNA and protein levels in oral cancer tissues and to …


Immunophenotypic Profile Of Acute Leukemias At Agakhan University Hospital, Nairobi, Beatrice M. Kabera Jul 2010

Immunophenotypic Profile Of Acute Leukemias At Agakhan University Hospital, Nairobi, Beatrice M. Kabera

Master of Medicine in Clinical Pathology

Background: Reliable distinction between AML and ALL is important for the selection of appropriate therapy. The final diagnosis of acute leukemia should be based on clinico-pathological, morphological, cytochemical and molecular cytogenetics data, together with immunophenotypic information. Flow cytometry has become the preferred method for the lineage assignment and maturational analysis of malignant cells in acute leukemias. Immunophenotyping has also allowed the detection of aberrant antigen co expression and the analysis of heterogeneity and clonality of malignant cells in acute leukemias. It is insufficient to merely make a diagnosis of acute leukemia, or even AML or ALL. Further classification is essential …


Teratology Primer-2nd Edition (7/9/2010), Sura Alwan, Steven B. Bleyl, Robert L. Brent, Christina D. Chambers, George P. Daston, Elaine M. Faustman, Richard H. Finnell, F. Clarke Fraser, Jan M. Freidman, Adriane Fugh-Berman, John M. Graham, Jr., Barbara F. Hales, Deborah K. Hansen, Lewis B. Holmes, Ronald D. Hood, Robert J. Kavlock, Thomas B. Knudsen, Joseph Lary, Donald R. Mattison, Richard K. Miller, James L. Mills, Janine E. Polifka, Sonja A. Rasmussen, Bernard Robaire, John M. Rogers, Gary C. Schoenwolf, Anthony R. Scialli, Gary M. Shaw, Amar V. Singh, William Slikker, Jr., Ann P. Streissguth, Melissa S. Tassinari, Janet Uriu-Adams, Charles V. Vorhees, Elora J. Weringer Jul 2010

Teratology Primer-2nd Edition (7/9/2010), Sura Alwan, Steven B. Bleyl, Robert L. Brent, Christina D. Chambers, George P. Daston, Elaine M. Faustman, Richard H. Finnell, F. Clarke Fraser, Jan M. Freidman, Adriane Fugh-Berman, John M. Graham, Jr., Barbara F. Hales, Deborah K. Hansen, Lewis B. Holmes, Ronald D. Hood, Robert J. Kavlock, Thomas B. Knudsen, Joseph Lary, Donald R. Mattison, Richard K. Miller, James L. Mills, Janine E. Polifka, Sonja A. Rasmussen, Bernard Robaire, John M. Rogers, Gary C. Schoenwolf, Anthony R. Scialli, Gary M. Shaw, Amar V. Singh, William Slikker, Jr., Ann P. Streissguth, Melissa S. Tassinari, Janet Uriu-Adams, Charles V. Vorhees, Elora J. Weringer

Department of Pediatrics Faculty Papers

Foreword:

What is Teratology?

“What a piece of work is an embryo!” as Hamlet might have said. “In form and moving how express and admirable! In complexity how infinite!” It starts as a single cell, which by repeated divisions gives rise to many genetically identical cells. These cells receive signals from their surroundings and from one another as to where they are in this ball of cells —front or back, right or left, headwards or tailwards, and what they are destined to become. Each cell commits itself to being one of many types; the cells migrate, combine into tissues, or …


The Role Of Gender In Single Vs Married Individuals With Bipolar Disorder., Daniel Z Lieberman, Suena H Massey, Frederick K Goodwin Jul 2010

The Role Of Gender In Single Vs Married Individuals With Bipolar Disorder., Daniel Z Lieberman, Suena H Massey, Frederick K Goodwin

Psychiatry and Behavioral Sciences Faculty Publications

BACKGROUND: Despite the importance of marriage as a source of social support, it has been largely neglected in studies of bipolar disorder; and differential effects on men and women have not been explored.

METHODS: Data on episodes of depression, mania, and mixed states were collected for the previous 2 years from a sample of 282 bipolar individuals using the National Institute of Mental Health Life Chart Methodology.

RESULTS: Effects unique to women included the following: Bipolar women were significantly more likely to be married. Married women had fewer episodes of depression during the past 2 years than never-married women, and …


A Randomized Comparison Of Online And Paper Mood Charts For People With Bipolar Disorder., Daniel Z Lieberman, Tammas F Kelly, Lanny Douglas, Frederick K Goodwin Jul 2010

A Randomized Comparison Of Online And Paper Mood Charts For People With Bipolar Disorder., Daniel Z Lieberman, Tammas F Kelly, Lanny Douglas, Frederick K Goodwin

Psychiatry and Behavioral Sciences Faculty Publications

BACKGROUND: Longitudinal mood instability is the essential feature of bipolar disorder, however most rating scales are cross sectional in nature, and focus on acute symptoms. By contrast, the NIMH Life Chart Methodology (LCM) characterizes in detail the severity, duration, and frequency of mood episodes. Adherence to daily rating, however, tends to be low. In this study an online version of the LCM, designed to enhance adherence, was compared to the standard paper version.

METHODS: Patients from a mood disorders specialty clinic were randomized to the standard LCM or an online, open-source adaptation. The online version used hypertext links embedded in …


Human Papillomavirus And Survival Of Patients With Oropharyngeal Cancer., K Kian Ang, Jonathan Harris, Richard Wheeler, Randal Weber, David I Rosenthal, Phuc Felix Nguyen-Tân, William H Westra, Christine H Chung, Richard C Jordan, Charles Lu, Harold Kim, Rita S. Axelrod, Md, C Craig Silverman, Kevin P Redmond, Maura L Gillison Jul 2010

Human Papillomavirus And Survival Of Patients With Oropharyngeal Cancer., K Kian Ang, Jonathan Harris, Richard Wheeler, Randal Weber, David I Rosenthal, Phuc Felix Nguyen-Tân, William H Westra, Christine H Chung, Richard C Jordan, Charles Lu, Harold Kim, Rita S. Axelrod, Md, C Craig Silverman, Kevin P Redmond, Maura L Gillison

Jefferson Hospital Staff Papers and Presentations

BACKGROUND: Oropharyngeal squamous-cell carcinomas caused by human papillomavirus (HPV) are associated with favorable survival, but the independent prognostic significance of tumor HPV status remains unknown.

METHODS: We performed a retrospective analysis of the association between tumor HPV status and survival among patients with stage III or IV oropharyngeal squamous-cell carcinoma who were enrolled in a randomized trial comparing accelerated-fractionation radiotherapy (with acceleration by means of concomitant boost radiotherapy) with standard-fractionation radiotherapy, each combined with cisplatin therapy, in patients with squamous-cell carcinoma of the head and neck. Proportional-hazards models were used to compare the risk of death among patients with HPV-positive …


Oncolog Volume 55, Number 07, July 2010, Joe Munch, Sunni Hoseman Jul 2010

Oncolog Volume 55, Number 07, July 2010, Joe Munch, Sunni Hoseman

OncoLog MD Anderson's Report to Physicians (All issues) Archives

  • Refining Approaches to Thyroid Cancer: Time-proven treatments and newer biologic agents offer hope, particularly for patirnts with advanced disease.
  • Thyroid Cancer in Children.
  • Compass Summer 2010: Locoregional Cancer of the Esophagus: Timimg Surgery and Other Therapies for Resectable Disease.
  • HOUSE CALL: Understanding Clinical Trials


Circadian Rhythms In Patients With St-Elevation Myocardial Infarction, Richard Aplin Md, Dr Holmes Md, Fv Acquirre Jul 2010

Circadian Rhythms In Patients With St-Elevation Myocardial Infarction, Richard Aplin Md, Dr Holmes Md, Fv Acquirre

Articles

BACKGROUND:

Circadian rhythms with regard to time of symptom onset for patients with acute myocardial infarction have been observed, although their relationship to outcomes has been debated. We evaluated these rhythms in patients with ST-elevation myocardial infarction as a function of the 24-hour circadian cycle.

METHODS AND RESULTS:

The relationship between onset of symptoms during the 24-hour circadian cycle and prehospital delays from symptom onset to hospital arrival, timeliness of reperfusion, and in-hospital death was assessed in 2143 patients with ST-elevation myocardial infarction presenting from 2004-2008 at 1 of 3 tertiary-care healthcare ST-elevation myocardial infarction systems. There was …


Is There An Optimal Management For Localized Prostate Cancer?, Jaspreet Singh, Edouard J. Trabulsi, Leonard G. Gomella Jul 2010

Is There An Optimal Management For Localized Prostate Cancer?, Jaspreet Singh, Edouard J. Trabulsi, Leonard G. Gomella

Department of Urology Faculty Papers

Widespread screening with prostate-specific antigen (PSA) has led to a significant increase in the detection of early stage, clinically localized prostate cancer (CaP). Various ­treatment options for localized CaP are discussed in this review article including active ­surveillance, radical prostatectomy, radiation therapy, and cyrotherapy. The paucity of high-level evidence adds a considerable amount of controversy when choosing the “optimal” ­intervention, for both the treating physician and the patient. The long time course of CaP intervention outcomes, combined with continuing modifications in treatments, further complicate the ­matter. Lacking randomized trials that compare treatment options, this review article attempts to summarize the …


Gsk-3alpha Directly Regulates Beta-Adrenergic Signaling And The Response Of The Heart To Hemodynamic Stress In Mice., Jibin Zhou, Hind Lal, Xiongwen Chen, Xiying Shang, Jianliang Song, Yingxin Li, Risto Kerkela, Bradley W Doble, Katrina Macaulay, Morgan Decaul, Walter J Koch, John Farber, James Woodgett, Erhe Gao, Thomas Force Jul 2010

Gsk-3alpha Directly Regulates Beta-Adrenergic Signaling And The Response Of The Heart To Hemodynamic Stress In Mice., Jibin Zhou, Hind Lal, Xiongwen Chen, Xiying Shang, Jianliang Song, Yingxin Li, Risto Kerkela, Bradley W Doble, Katrina Macaulay, Morgan Decaul, Walter J Koch, John Farber, James Woodgett, Erhe Gao, Thomas Force

Center for Translational Medicine Faculty Papers

The glycogen synthase kinase-3 (GSK-3) family of serine/threonine kinases consists of 2 highly related isoforms, alpha and beta. Although GSK-3beta has an important role in cardiac development, much remains unknown about the function of either GSK-3 isoform in the postnatal heart. Herein, we present what we believe to be the first studies defining the role of GSK-3alpha in the mouse heart using gene targeting. Gsk3a(-/-) mice over 2 months of age developed progressive cardiomyocyte and cardiac hypertrophy and contractile dysfunction. Following thoracic aortic constriction in young mice, we observed enhanced hypertrophy that rapidly transitioned to ventricular dilatation and contractile dysfunction. …


Histamine Reduces Flash Sensitivity Of On Ganglion Cells In The Primate Retina, Nikolay P Akimov, David W Marshak, Laura J Frishman, Randolph D Glickman, Rafail G Yusupov Jul 2010

Histamine Reduces Flash Sensitivity Of On Ganglion Cells In The Primate Retina, Nikolay P Akimov, David W Marshak, Laura J Frishman, Randolph D Glickman, Rafail G Yusupov

Faculty, Staff and Student Publications

PURPOSE. In Old World primates, the retina receives input from histaminergic neurons in the posterior hypothalamus. They are a subset of the neurons that project throughout the central nervous system and fire maximally during the day. The contribution of these neurons to vision, was examined by applying histamine to a dark-adapted, superfused baboon eye cup preparation while making extracellular recordings from peripheral retinal ganglion cells. METHODS. The stimuli were 5-ms, 560-nm, weak, full-field flashes in the low scotopic range. Ganglion cells with sustained and transient ON responses and two cell types with OFF responses were distinguished; their responses were recorded …


Outcomes After Implantation Of The Taxus Paclitaxel-Eluting Stent In Saphenous Vein Graft Lesions: Results From The Arrive (Taxus Peri-Approval Registry: A Multicenter Safety Surveillance) Program, Emmanouil S. Brilakis Md, Phd, John M. Lasala Md, Phd, David A. Cox Md, Peter B. Berger Md, Thomas S. Bowman Md, Mph, Ruth M. Starzyk Phd, Keith D. Dawkins Md Jul 2010

Outcomes After Implantation Of The Taxus Paclitaxel-Eluting Stent In Saphenous Vein Graft Lesions: Results From The Arrive (Taxus Peri-Approval Registry: A Multicenter Safety Surveillance) Program, Emmanouil S. Brilakis Md, Phd, John M. Lasala Md, Phd, David A. Cox Md, Peter B. Berger Md, Thomas S. Bowman Md, Mph, Ruth M. Starzyk Phd, Keith D. Dawkins Md

Department of Medicine

No abstract provided.


Updating The Dermatologic Nomenclature: Names That Are Good Or Bad., Lawrence Charles Parish, Joseph A. Witkowski Jul 2010

Updating The Dermatologic Nomenclature: Names That Are Good Or Bad., Lawrence Charles Parish, Joseph A. Witkowski

Department of Dermatology and Cutaneous Biology Faculty Papers

Dermatology probably has the largest vocabulary of any of the medical specialties,1 a statement to which we can attest when we reviewed aspects of the Dermatology Lexicon project. Some terms are derived from the Latin or Greek and present spelling problems to all but a select few. Examples include acrokeratosis verruciformis and pterigium. Other diseases carry names that are such a mouthful that few can call them out without the interruption of breathing. These might include erosio interdigitalis blastomycetica and dermatitis exudative discoid and lichenoid of Sulzberger and Garbe. No wonder the former is now referred to simply as …


Expression Patterns Of Β–Catenin, Cox-2 And P27 In Colorectal Carcinomas At Aga Khan University Hospital, Nairobi, Patricia Okiro Jun 2010

Expression Patterns Of Β–Catenin, Cox-2 And P27 In Colorectal Carcinomas At Aga Khan University Hospital, Nairobi, Patricia Okiro

Master of Medicine in Anatomic Pathology

Introduction: Colorectal cancer is the third most common cancer worldwide, as indicated by WHO. Local published and unpublished data indicate that patients in the developing world with colorectal cancer tend to present at an early age, and possibly at a more advanced stage than described in the developed world. The reason for this difference is unclear, and as yet undefined. The Wnt/APC pathway, Microsatellite instability pathway and the Epigenetic pathway are three pathogenetically distinct pathways that have been implicated in the development of colorectal cancer. Exploration of these patterns may allow us to elucidate possible reasons for these differences. Objectives: …


Anti-Hiv Activity In Cervical-Vaginal Secretions From Hiv-Positive And -Negative Women Correlate With Innate Antimicrobial Levels And Igg Antibodies, Mimi Ghosh, John V. Fahey, Zheng Shen, Timothy Lahey, Susan Cu-Uvin, Zhijin Wu, Kenneth Mayer, Peter F. Wright, John C. Kappes, Christina Ochsenbauer, Charles R. Wira Jun 2010

Anti-Hiv Activity In Cervical-Vaginal Secretions From Hiv-Positive And -Negative Women Correlate With Innate Antimicrobial Levels And Igg Antibodies, Mimi Ghosh, John V. Fahey, Zheng Shen, Timothy Lahey, Susan Cu-Uvin, Zhijin Wu, Kenneth Mayer, Peter F. Wright, John C. Kappes, Christina Ochsenbauer, Charles R. Wira

Dartmouth Scholarship

Background: We investigated the impact of antimicrobials in cervicovaginal lavage (CVL) from HIV(+) and HIV(2) women on target cell infection with HIV. Since female reproductive tract (FRT) secretions contain a spectrum of antimicrobials, we hypothesized that CVL from healthy HIV(+) and (2) women inhibit HIV infection.

Methodology/Principal Findings: CVL from 32 HIV(+) healthy women with high CD4 counts and 15 healthy HIV(2) women were collected by gently washing the cervicovaginal area with 10 ml of sterile normal saline. Following centrifugation, anti- HIV activity in CVL was determined by incubating CVL with HIV prior to addition to TZM-bl cells. Antimicrobials and …


The Efficacy And Safety Of Insulin-Sensitizing Drugs In Hiv-Associated Lipodystrophy Syndrome: A Meta-Analysis Of Randomized Trials, Siddharth H. Sheth, Robin J. Larson Jun 2010

The Efficacy And Safety Of Insulin-Sensitizing Drugs In Hiv-Associated Lipodystrophy Syndrome: A Meta-Analysis Of Randomized Trials, Siddharth H. Sheth, Robin J. Larson

Dartmouth Scholarship

HIV-associated lipodystrophy syndrome (HALS) is characterized by insulin resistance, abnormal lipid metabolism and redistribution of body fat. To date, there has been no quantitative summary of the effects of insulin sensitizing-agents for the treatment of this challenging problem. We searched MEDLINE, the Cochrane Library, clinical trial registries, conference proceedings and references for randomized trials evaluating rosiglitazone, pioglitazone or metformin in patients with evidence of HALS (last update December 2009). Two reviewers independently abstracted data and assessed quality using a standard form. We contacted authors for missing data and calculated weighted mean differences (WMD) and 95% confidence intervals (CI) for each …


Ros Accumulation And Igf-Ir Inhibition Contribute To Fenofibrate/Pparalpha -Mediated Inhibition Of Glioma Cell Motility In Vitro, Justyna Drukala, Katarzyna Urbanska, Anna Wilk, Maja Grabacka, Ewa Wybieralska, Luis Del Valle, Zbigniew Madeja, Krzysztof Reiss Jun 2010

Ros Accumulation And Igf-Ir Inhibition Contribute To Fenofibrate/Pparalpha -Mediated Inhibition Of Glioma Cell Motility In Vitro, Justyna Drukala, Katarzyna Urbanska, Anna Wilk, Maja Grabacka, Ewa Wybieralska, Luis Del Valle, Zbigniew Madeja, Krzysztof Reiss

School of Medicine Faculty Publications

BACKGROUND: Glioblastomas are characterized by rapid cell growth, aggressive CNS infiltration, and are resistant to all known anticancer regimens. Recent studies indicate that fibrates and statins possess anticancer potential. Fenofibrate is a potent agonist of peroxisome proliferator activated receptor alpha (PPARalpha) that can switch energy metabolism from glycolysis to fatty acid beta-oxidation, and has low systemic toxicity. Fenofibrate also attenuates IGF-I-mediated cellular responses, which could be relevant in the process of glioblastoma cell dispersal. METHODS: The effects of fenofibrate on Glioma cell motility, IGF-I receptor (IGF-IR) signaling, PPARalpha activity, reactive oxygen species (ROS) metabolism, mitochondrial potential, and ATP production were …


Is Phonophobia Associated With Cutaneous Allodynia In Migraine?, Avi Ashkenazi, Irene Yang, Aamir Mushtaq, Michael L. Oshinsky Jun 2010

Is Phonophobia Associated With Cutaneous Allodynia In Migraine?, Avi Ashkenazi, Irene Yang, Aamir Mushtaq, Michael L. Oshinsky

Department of Neurology Faculty Papers

ABSTRACT

Objective

To determine whether phonophobia and dynamic mechanical (brush) allodynia are associated in episodic migraine (EM).

Methods

Adult patients with EM were prospectively recruited. A structured questionnaire was used to obtain demographic and migraine related data. Phonophobia was tested quantitatively using a real time sound processor and psychoacoustic software. Sound stimuli were pure tones at frequencies of 1000 Hz, 4000 Hz and 8000 Hz, delivered to both ears at increasing intensities, until an aversive level was reached. Allodynia was assessed by brushing the patient’s skin with a gauze pad at different areas. Patients were tested both between and during …


High-Throughput Experimental Studies To Identify Mirna Targets Directly, With Special Focus On The Mammalian Brain, Peter T. Nelson, Marianthi Kiriakidou, Zissimos Mourelatos, Grace S. Tan, Mary H. Jennings, Kevin Xie, Wang-Xia Wang Jun 2010

High-Throughput Experimental Studies To Identify Mirna Targets Directly, With Special Focus On The Mammalian Brain, Peter T. Nelson, Marianthi Kiriakidou, Zissimos Mourelatos, Grace S. Tan, Mary H. Jennings, Kevin Xie, Wang-Xia Wang

Pathology and Laboratory Medicine Faculty Publications

We review the pertinent literature on methods used in high-throughput experimental identification of microRNA (miRNA) "targets" with emphasis on neurochemical studies. miRNAs are short regulatory noncoding RNAs that play important roles in the mammalian brain. The functions of miRNAs are related to their binding of RNAs including mRNAs. Since mammalian miRNAs tend to bind to target mRNAs via imperfect complementarity, understanding exactly which target mRNAs are recognized by which specific miRNAs is a challenge. Based on early experimental evidence, a set of "binding rules" for miRNAs has been described. These have focused on the 5' "seed" region of miRNAs binding …


A Probit- Log- Skew-Normal Mixture Model For Repeated Measures Data With Excess Zeros, With Application To A Cohort Study Of Paediatric Respiratory Symptoms, Sadia Mahmud, W. Y. Wendy Lou, Neil W. Johnston Jun 2010

A Probit- Log- Skew-Normal Mixture Model For Repeated Measures Data With Excess Zeros, With Application To A Cohort Study Of Paediatric Respiratory Symptoms, Sadia Mahmud, W. Y. Wendy Lou, Neil W. Johnston

Community Health Sciences

Background: A zero-inflated continuous outcome is characterized by occurrence of "excess" zeros that more than a single distribution can explain, with the positive observations forming a skewed distribution. Mixture models are employed for regression analysis of zero-inflated data. Moreover, for repeated measures zero-inflated data the clustering structure should also be modeled for an adequate analysis. Methods: Diary of Asthma and Viral Infections Study (DAVIS) was a one year (2004) cohort study conducted at McMaster University to monitor viral infection and respiratory symptoms in children aged 5-11 years with and without asthma. Respiratory symptoms were recorded daily using either an Internet …


Mitochondria-Centric Activation Induced Cell Death Of Cytolytic T Lymphocytes And Its Implications For Cancer Immunotherapy, Arvind Chhabra Jun 2010

Mitochondria-Centric Activation Induced Cell Death Of Cytolytic T Lymphocytes And Its Implications For Cancer Immunotherapy, Arvind Chhabra

UCHC Articles - Research

Premature death of the adoptively transferred cytolytic T lymphocytes (CTL) by means of activation induced cell death (AICD) represents one of the major constraints in devising an effective anti-cancer immune intervention strategy. Understanding the mechanism of AICD is, therefore, critical for developing methods to interfere with this death process. Although the existing paradigm on AICD centers around the initiation of the cascade of events originating from the engagement of death receptors leading to the activation of effector caspases and eventually resulting in cell death, recent findings have questioned the universal role of caspases as the cell death executioners. We here …


Notch1 Functions As A Tumor Suppressor In A Model Of K-Ras–Induced Pancreatic Ductal Adenocarcinoma, Linda Hanlon, Jacqueline L Avila, Renée M Demarest, Scott Troutman, Megan Allen, Francesca Ratti, Anil K Rustgi, Ben Z Stanger, Fred Radtke, Volkan Adsay, Fenella Long, Anthony J Capobianco, Joseph L Kissil Jun 2010

Notch1 Functions As A Tumor Suppressor In A Model Of K-Ras–Induced Pancreatic Ductal Adenocarcinoma, Linda Hanlon, Jacqueline L Avila, Renée M Demarest, Scott Troutman, Megan Allen, Francesca Ratti, Anil K Rustgi, Ben Z Stanger, Fred Radtke, Volkan Adsay, Fenella Long, Anthony J Capobianco, Joseph L Kissil

Rowan-Virtua School of Osteopathic Medicine Departmental Research

K-ras is the most commonly mutated oncogene in pancreatic cancer and its activation in murine models is sufficient to recapitulate the spectrum of lesions seen in human pancreatic ductal adenocarcinoma (PDAC). Recent studies suggest that Notch receptor signaling becomes reactivated in a subset of PDACs, leading to the hypothesis that Notch1 functions as an oncogene in this setting. To determine whether Notch1 is required for K-ras-induced tumorigenesis, we used a mouse model in which an oncogenic allele of K-ras is activated and Notch1 is deleted simultaneously in the pancreas. Unexpectedly, the loss of Notch1 in this model resulted in increased …


Physiologically Based Pharmacokinetics Of Molecular Imaging Nanoparticles For Mrna Detection Determined In Tumor-Bearing Mice., Armin W Opitz, Eric Wickstrom, Mathew L Thakur, Norman J Wagner Jun 2010

Physiologically Based Pharmacokinetics Of Molecular Imaging Nanoparticles For Mrna Detection Determined In Tumor-Bearing Mice., Armin W Opitz, Eric Wickstrom, Mathew L Thakur, Norman J Wagner

Kimmel Cancer Center Faculty Papers

Disease detection and management might benefit from external imaging of disease gene mRNAs. Previously we designed molecular imaging nanoparticles (MINs) based on peptide nucleic acids complementary to cancer gene mRNAs. The MINs included contrast agents and analogs of insulin-like growth factor 1 (IGF-1). Analysis of MIN tumor uptake data showed stronger binding in tumors than in surrounding tissues. We hypothesized that MINs with an IGF-1 analog stay in circulation by binding to IGF-binding proteins. To test that hypothesis, we fit the tissue distribution results of several MINs in xenograft-bearing mice to a physiological pharmacokinetics model. Fitting experimental tissue distribution data …


Labrad : Vol 35, Issue 2 - June 2010, Aga Khan University Hospital, Karachi Jun 2010

Labrad : Vol 35, Issue 2 - June 2010, Aga Khan University Hospital, Karachi

LABRAD - Departments of Pathology & Laboratory Medicine and Radiology Archives

  • The Atypical Lymphocytes
  • High Performance Liquid Chromatography (HPLC): An Effective Tool for the Diagnosis of Various Hemoglobinopathies
  • Platelet Transfusions: What We Need to Know
  • Measuring Homocysteine Levels
  • Parathyroid Hormone: A Marker of Vitamin D Deficiency and Insufficiency
  • Surrogate Measures of Insulin Sensitivity
  • Foetal Autopsy
  • Laboratory Diagnosis of Vaginitis due to Trichomonas Vaginalis
  • AKU Clinical Laboratory Continuing Medical Education Seminars


Association Between Obesity, Depression, And Inflammation Among Seventh-Day Adventists In The Biopsychosocial Religion And Health Study, Michael Paalani Jun 2010

Association Between Obesity, Depression, And Inflammation Among Seventh-Day Adventists In The Biopsychosocial Religion And Health Study, Michael Paalani

Loma Linda University Electronic Theses, Dissertations & Projects

The effects of obesity and depression on morbidity and mortality may be mediated by inflammatory processes. Homeostasis within the immune system depends on a balance of pro-inflammatory and anti-inflammatory cytokine molecules, so chronic inflammatory diseases may result from cytokine dysregulation. The target population consisted of 508 Seventh Day Adventists (SDAs) who participated in the Biopsychosocial Religion and Health Study (BHRS), a sub-study of the Adventist Health Study-2. The study was a cross-sectional analysis of the association between obesity, depression, and inflammation after controlling for demographic, socioeconomic, health behavioral, and health status variables among BHRS participants.

Obesity was assessed by body …


Emergency Department Staff Adherence To Bad News Delivery Recommendations, Kristen R. Myers Jun 2010

Emergency Department Staff Adherence To Bad News Delivery Recommendations, Kristen R. Myers

Loma Linda University Electronic Theses, Dissertations & Projects

Emergency department (ED) staff is responsible for giving bad news regarding death, diagnoses, and other traumatic losses to patients and loved ones. Individuals receiving traumatic and sudden bad news are at increased risk of serious psychological and physiological consequences of disrupted grief. Despite published recommended practices for providers to help prevent maladaptive grief responses, little research is available on actual bad news delivery practices and factors promoting or hindering adherence to recommendations, and no study specifically explored the ED context.

The study used a qualitative design to explore bad news delivery practices, awareness of recommendations, factors perceived to hinder or …