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2009

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Articles 271 - 300 of 4384

Full-Text Articles in Medicine and Health Sciences

Tb Research At Ut-Houston – A Review Of Cord Factor: New Approaches To Drugs, Vaccines And The Pathogenesis Of Tuberculosis, Robert L Hunter, Lisa Armitige, Chinnaswamy Jagannath, Jeffrey K Actor Dec 2009

Tb Research At Ut-Houston – A Review Of Cord Factor: New Approaches To Drugs, Vaccines And The Pathogenesis Of Tuberculosis, Robert L Hunter, Lisa Armitige, Chinnaswamy Jagannath, Jeffrey K Actor

Faculty, Staff and Student Publications

Tuberculosis remains a major threat as drug resistance continues to increase. Pulmonary tuberculosis in adults is responsible for 80% of clinical cases and nearly 100% of transmission of infection. Unfortunately, since we have no animal models of adult type pulmonary tuberculosis, the most important type of disease remains largely out of reach of modern science and many fundamental questions remain unanswered. This paper reviews research dating back to the 1950's providing compelling evidence that cord factor (trehalose 6,6 dimycolate [TDM]) is essential for understanding tuberculosis. However, the original papers by Bloch and Noll were too far ahead of their time …


Association Tests Of The Opioid Receptor System And Alcohol-Related Traits, Ryan Bennett Dec 2009

Association Tests Of The Opioid Receptor System And Alcohol-Related Traits, Ryan Bennett

Theses and Dissertations

The opioid receptors and their endogenous ligands have long been implicated in a variety of traits including addiction, impulsive behaviors and substance dependence. Using phenotypic measurements collected from the IASPSAD, data from a latent class analysis and data from a SNP array and additional genotyping assays, association and regression tests were performed to determine the effects of common SNPs encoded in the genes of the opioid receptors and ligands on various traits relating to alcohol dependence. Although only one SNP can be reported as significant for substance dependence within alcoholics, there were a few results approaching significance that may offer …


Analysis Of Genetic Variability And Whole Genome Linkage Of Whole-Brain, Subcortical, And Ependymal Hyperintense White Matter Volume, Peter Kochunov, David Glahn, Anderson M. Winkler, Ravi Duggirala, Rene L. Olvera, Shelley A. Cole, Thomas D. Dyer, Laura Almasy, Peter T. Fox, John Blangero Dec 2009

Analysis Of Genetic Variability And Whole Genome Linkage Of Whole-Brain, Subcortical, And Ependymal Hyperintense White Matter Volume, Peter Kochunov, David Glahn, Anderson M. Winkler, Ravi Duggirala, Rene L. Olvera, Shelley A. Cole, Thomas D. Dyer, Laura Almasy, Peter T. Fox, John Blangero

School of Medicine Publications

Background and purpose: The cerebral volume of T2-hyperintense white matter (HWM) is an important neuroimaging marker of cerebral integrity. Pathophysiology studies identified that subcortical and ependymal HWM are produced by 2 different mechanisms but shared a common risk factor: high arterial pulse pressure. Recent studies have demonstrated high heritability of the whole-brain HMW volume and reported significant and suggestive evidence of genetic linkage. We performed heritability and whole-genome linkage analysis to replicate previous reported findings and to study shared genetic variance, and possible overlap for specific loci, between subcortical and ependymal HWM volumes in a population of healthy Mexican Americans. …


The 'Molar Tooth Sign' In Joubert Syndrome, Imaad Ur Rehman, Zablon Bett, Yousuf Husen, Ali Syed Muhammad Akhtar, Faisal Aziz Khan Dec 2009

The 'Molar Tooth Sign' In Joubert Syndrome, Imaad Ur Rehman, Zablon Bett, Yousuf Husen, Ali Syed Muhammad Akhtar, Faisal Aziz Khan

Department of Radiology

The molar tooth sign is seen in very few conditions and is a very rare paediatric central nervous system congenital anomaly. Molar tooth sign is the result of cerebellar vermis hypoplasia, thick and maloriented superior cerebellar peduncles, and an abnormally deep interpeduncular fossa. In Joubert syndrome this is seen in about 85% of patients. We present a case of 13 months old baby boy with recurrent episodes of fits and hyperpnoea, regression of milestones and developmental delay. MRI examination showed the characteristic molar tooth sign with apposition of cerebellar hemispheres, batwing-shaped fourth ventricle communicating through a thin fissure with foramen …


The Burden Of Stroke And Transient Ischemic Attack In Pakistan: A Community-Based Prevalence Study, Ayeesha Kamran Kamal, Ahmed Itrat, Muhammed Murtaza, Maria Khan, Asif Rasheed, Amin Ali, Amna Akber, Zainab Akber, Naved Iqbal, Sana Shoukat, Farzin Majeed, Danish Saleheen Dec 2009

The Burden Of Stroke And Transient Ischemic Attack In Pakistan: A Community-Based Prevalence Study, Ayeesha Kamran Kamal, Ahmed Itrat, Muhammed Murtaza, Maria Khan, Asif Rasheed, Amin Ali, Amna Akber, Zainab Akber, Naved Iqbal, Sana Shoukat, Farzin Majeed, Danish Saleheen

Section of Neurology

Background: The burden of cerebrovascular disease in developing countries is rising sharply. The prevalence of established risk factors of stroke is exceptionally high in Pakistan. However, there is limited data on the burden of stroke and transient ischemic attack (TIA) in South Asia. We report the first such study conducted in an urban slum of Karachi, Pakistan. Methods:Individuals 35 years of age or older were invited for participation in this investigation through simple random sampling. A structured face-to-face interview was conducted using a pretested stroke symptom questionnaire in each participant to screen for past stroke or TIA followed by …


Biological Diversity Of Prokaryotic Type Iv Secretion Systems, Cristina E Alvarez-Martinez, Peter J Christie Dec 2009

Biological Diversity Of Prokaryotic Type Iv Secretion Systems, Cristina E Alvarez-Martinez, Peter J Christie

Faculty, Staff and Student Publications

Type IV secretion systems (T4SS) translocate DNA and protein substrates across prokaryotic cell envelopes generally by a mechanism requiring direct contact with a target cell. Three types of T4SS have been described: (i) conjugation systems, operationally defined as machines that translocate DNA substrates intercellularly by a contact-dependent process; (ii) effector translocator systems, functioning to deliver proteins or other macromolecules to eukaryotic target cells; and (iii) DNA release/uptake systems, which translocate DNA to or from the extracellular milieu. Studies of a few paradigmatic systems, notably the conjugation systems of plasmids F, R388, RP4, and pKM101 and the Agrobacterium tumefaciens VirB/VirD4 system, …


Mindfulness Meditation And Art Making: Implications For Art Therapy, Susan Kathleen Mahl Dec 2009

Mindfulness Meditation And Art Making: Implications For Art Therapy, Susan Kathleen Mahl

EVMS School of Health Professions Theses & Dissertations

Meditation is being integrated into various fields to aid with healing, especially mindfulness meditation as it focuses on total awareness of the present. This thesis describes a self study that used a heuristic methodology to investigate the effects of mindfulness meditation on this researcher. I progressed through the six phases of heuristic research in a period seven weeks. At the beginning of the study, mindfulness meditation was practiced twice a week for a time period of 30 minutes to one hour for three weeks, followed by art making and reflections. Next, I practiced mindfulness meditation three times a week for …


Efficiency And Cost Of A Hospital-Based Medical Home: Children With Special Healthcare Needs, Rebecca Olsen Nov 2009

Efficiency And Cost Of A Hospital-Based Medical Home: Children With Special Healthcare Needs, Rebecca Olsen

Florida Public Health Review

The current study examined two years of pre-post hospital utilization data (the number of emergency room visits, number of unanticipated hospitalizations, and length of stay (LOS)) among forty-nine medically complex children to determine the efficiency and cost effectiveness of a comprehensive Hospital-Based Medical Home Model. Friedman nonparametric analysis was used to examine the pre-post differences for the non-normal distribution. Each of the cost-effectiveness measures (number of emergency room visits, number of unanticipated hospitalizations, and LOS) were found to be significantly lower post enrollment in the Hospital-Based Medical Home Model.


Food For Thought: The Importance Of Nutrition For Cognitive And Physical Well-Being, Keeley M. Caviness Nov 2009

Food For Thought: The Importance Of Nutrition For Cognitive And Physical Well-Being, Keeley M. Caviness

Senior Honors Theses

The purpose of this paper is to examine the effects of nutrition upon the physical development and health of an individual. The main focus is on proving through the examination of various literature and the effects of specific nutrients that nutrition has a great impact on mental and physical well-being. The reasons which people give for not having proper nutrition are taken into consideration as well, and an overall conclusion can be made that nutrition is very important and should be taught to all consumers.


Medical School Watercooler Newsletter - November 29, 2009, Lindsey Lyle Nov 2009

Medical School Watercooler Newsletter - November 29, 2009, Lindsey Lyle

Watercooler Newsletter

This is the November 29, 2009 edition of the Frederick P. Whiddon College of Medicine's newsletter - Watercooler

Contents Include:

  • USA Medical Student Participate in Dr. Pepper Challenge at SEC Championship

  • December 10th DSS - "Intersection Between Coagulation and Inflammation: The Secret Life of Coagulation Factors"

  • December Med School Cafe' - RSVP Now!

  • USA Faculty Make "House Calls" to Local College

  • Contruction Tour - New Dialysis Center at USAMC

  • For Starters - Get Your Vaccinations NOW!

  • Mammograms: When To Test?

  • Born to be a Doctor

  • December Distinguished Scientist Seminar

  • Benny Booker Remembered

  • November Med School Cafe' lecture - Online Now!


Prospective Associations Between Objective Measures Of Physical Activity And Fat Mass In 12-14 Year Old Children: The Avon Longitudinal Study Of Parents And Children (Alspac), Chris J. Riddoch, Sam D. Leary, Andy R. Ness, Steven N. Blair, Kevin Deere, Calum Mattocks, Alex Griffiths, George Davey Smith, Kate Tilling Nov 2009

Prospective Associations Between Objective Measures Of Physical Activity And Fat Mass In 12-14 Year Old Children: The Avon Longitudinal Study Of Parents And Children (Alspac), Chris J. Riddoch, Sam D. Leary, Andy R. Ness, Steven N. Blair, Kevin Deere, Calum Mattocks, Alex Griffiths, George Davey Smith, Kate Tilling

Faculty Publications

Objective: To investigate associations between physical activity at age 12 and subsequent adiposity at age 14.

Design: Prospective birth cohort study with data collected between 2003 and 2007.

Setting: Original recruitment in 1991-2 of 14,541 pregnant women living in the former County of Avon (United Kingdom).

Participants: At age 12, 11,952 children were invited to attend the research clinic. Of these, 7159 attended, and 4150 (1964 boys, 2186 girls) provided sufficient data on exposure, outcome, and confounding variables.

Main outcome measure: Fat mass at age 14, measured by dual emission x ray absorptiometry, associated with physical activity at age 12, …


The Impact Of Left Hemisphere Stroke On Force Control With Familiar And Novel Objects: Neuroanatomic Substrates And Relationship To Apraxia, Amanda M. Dawson, Laura J. Buxbaum, Susan V. Duff Nov 2009

The Impact Of Left Hemisphere Stroke On Force Control With Familiar And Novel Objects: Neuroanatomic Substrates And Relationship To Apraxia, Amanda M. Dawson, Laura J. Buxbaum, Susan V. Duff

Physical Therapy Faculty Articles and Research

Fingertip force scaling for lifting objects frequently occurs in anticipation of finger contact. An ongoing question concerns the types of memories that are used to inform predictive control. Object-specific information such as weight may be stored and retrieved when previously encountered objects are lifted again. Alternatively, visual size and shape cues may provide estimates of object density each time objects are encountered. We reasoned that differences in performance with familiar versus novel objects would provide support for the former possibility. Anticipatory force production with both familiar and novel objects was assessed in six left hemisphere stroke patients, two of whom …


Today - November 25, 2009, Loma Linda University Nov 2009

Today - November 25, 2009, Loma Linda University

TODAY

Inside this issue:

-- Jamaican governor-general visits Loma Linda University
-- ThankSharing program evokes spirit of gratitude and volunteerism
-- Big Hearts for Little Hearts Loma Linda Guild hosts ‘Food, Fashion, and Fun’ to benefit LLU Children’s Hospital
-- More than 6,000 participate in second annual ‘Believe and Walk for the Cure’
-- Promising research suggests a method for healing difficult wounds
-- The skies thunder over LLU Children’s Hospital during the 11th Annual Cops for Kids Fly-in
-- Fourth graders from surrounding communities receive free bicycles
-- School of Religion to present two events December 4 and 5
-- …


Smelling The Flowers At Thanksgiving, Kenneth P. Serbin Nov 2009

Smelling The Flowers At Thanksgiving, Kenneth P. Serbin

At Risk for Huntington's Disease

No abstract provided.


Dopamine-Stimulated Dephosphorylation Of Connexin 36 Mediates Aii Amacrine Cell Uncoupling, W Wade Kothmann, Stephen C Massey, John O'Brien Nov 2009

Dopamine-Stimulated Dephosphorylation Of Connexin 36 Mediates Aii Amacrine Cell Uncoupling, W Wade Kothmann, Stephen C Massey, John O'Brien

Faculty, Staff and Student Publications

Gap junction proteins form the substrate for electrical coupling between neurons. These electrical synapses are widespread in the CNS and serve a variety of important functions. In the retina, connexin 36 (Cx36) gap junctions couple AII amacrine cells and are a requisite component of the high-sensitivity rod photoreceptor pathway. AII amacrine cell coupling strength is dynamically regulated by background light intensity, and uncoupling is thought to be mediated by dopamine signaling via D(1)-like receptors. One proposed mechanism for this uncoupling involves dopamine-stimulated phosphorylation of Cx36 at regulatory sites, mediated by protein kinase A. Here we provide evidence against this hypothesis …


Effects Of Cannabinoid Receptor Interacting Protein (Crip1a) On Cannabinoid Receptor (Cb1) Function, Tricia Smith Nov 2009

Effects Of Cannabinoid Receptor Interacting Protein (Crip1a) On Cannabinoid Receptor (Cb1) Function, Tricia Smith

Theses and Dissertations

EFFECTS OF CANNABINOID RECEPTOR INTERACTING PROTEIN (CRIP1a) ON CANNABINOID (CB1) RECEPTOR FUNCTION. By Tricia Hardt Smith, B.S., M.S. A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy at Virginia Commonwealth University Virginia Commonwealth University, 2009. Major Director: Dana E. Selley, Ph.D., Department of Pharmacology and Toxicology This dissertation examines modulation of cannabinoid CB1 receptor function by Cannabinoid Receptor Interacting Protein (CRIP1a), a novel protein that binds the C-terminus of CB1 receptors. In Human embryonic kidney cells expressing human CB1 receptors (hCB1-HEK) and hCB1-HEK cells stably co-expressing CRIP1a (hCB1-HEK-CRIP1a), quantitative immunoblotting revealed a CRIP1a/CB1 …


Immigrant Granite Installer Killed After Falling With Homemade Construction Box, Kentucky Injury Prevention And Research Center Nov 2009

Immigrant Granite Installer Killed After Falling With Homemade Construction Box, Kentucky Injury Prevention And Research Center

Fatality Case Reports--Falls

On a summer day in 2009, a 50-year-old granite installer and his two sons were working alone at a construction site when the granite installer fell out of a second story window and was killed. The three granite installers worked for a subcontractor hired to install granite vanity tops and sinks in a newly constructed hotel. Work had commenced at 7:00 AM that morning. They were installing the second set of ten vanities for the day. All ten vanities, with back and side splash pieces, had been loaded onto a homemade three-sided construction box and lifted via a forklift to …


Detection Of Sub-Clinical Cwd Infection In Conventional Test-Negative Deer Long After Oral Exposure To Urine And Feces From Cwd+ Deer, Nicholas J. Haley, Candace K. Mathiason, Mark D. Zabel, Glenn C. Telling, Edward A Hoover Nov 2009

Detection Of Sub-Clinical Cwd Infection In Conventional Test-Negative Deer Long After Oral Exposure To Urine And Feces From Cwd+ Deer, Nicholas J. Haley, Candace K. Mathiason, Mark D. Zabel, Glenn C. Telling, Edward A Hoover

Microbiology, Immunology, and Molecular Genetics Faculty Publications

BACKGROUND: Chronic wasting disease (CWD) of cervids is a prion disease distinguished by high levels of transmissibility, wherein bodily fluids and excretions are thought to play an important role. Using cervid bioassay and established CWD detection methods, we have previously identified infectious prions in saliva and blood but not urine or feces of CWD+ donors. More recently, we identified very low concentrations of CWD prions in urine of deer by cervid PrP transgenic (Tg[CerPrP]) mouse bioassay and serial protein misfolding cyclic amplification (sPMCA). This finding led us to examine further our initial cervid bioassay experiments using sPMCA.

OBJECTIVES: We sought …


Synthesis And Evaluation Of Anibamine And Its Analogs As Novel Anti-Prostate Cancer Agents, Kendra Haney Nov 2009

Synthesis And Evaluation Of Anibamine And Its Analogs As Novel Anti-Prostate Cancer Agents, Kendra Haney

Theses and Dissertations

The chemokine receptor CCR5 has been implicated in the pathogenesis of prostate cancer. A novel natural product, anibamine, was isolated and found to be a micromolar inhibitor of the receptor. Anibamine was used as a new anti-prostate cancer lead compound. To discover the pharmacophore, analogs of anibamine were designed using the “deconstruction-reconstruction-elaboration” approach and synthesized. The establishment of a stereoselective route to only one isomer was explored, to increase yield and eliminate elaborate purification procedures. Analogs were found to have anti-prostate cancer activity at levels higher than the parent compound. The molecular modeling studies of the deconstructed analogs indicate that …


Medical School Watercooler Newsletter - November 22, 2009, Lindsey Lyle Nov 2009

Medical School Watercooler Newsletter - November 22, 2009, Lindsey Lyle

Watercooler Newsletter

This is the November 22, 2009 edition of the Frederick P. Whiddon College of Medicine's newsletter - Watercooler

Contents Include:

  • Med School Cafe' - SRO at Mobile Museum of Art
  • Pediatric Resident To Be Featured
  • 3rd Annual USA COM Research Forum
  • H1N1 Vaccination Clinic at Mitchell Center
  • Endowed Eran & N.Q. Adams Lecture and Visiting Professorship in Neurology


Teaching A School-Based Aac Team To Support The Communication Skills Of A Student Who Requires Aac, Amy Thatcher Nov 2009

Teaching A School-Based Aac Team To Support The Communication Skills Of A Student Who Requires Aac, Amy Thatcher

Speech and Hearing Sciences ETDs

Many children of all ages are in need of augmentative and alternative communication (AAC). Adult communication partners in the school setting typically interact differently with children who use AAC than they do with others. In prior studies, an eight-step instructional program designed to teach adult communication partners to facilitate the communication skills of students who use AAC has been used within an individual instructional format. The eight-step instructional model used to teach these adults has been shown to be effective; however, research is required to establish the efficacy of this program when providing instruction to adult communication partners within group …


Survival Analysis With Error-Prone Time-Varying Covariates: A Risk Set Calibration Approach, Xiaomei Liao, David M. Zucker, Yi Li, Donna Spiegelman Nov 2009

Survival Analysis With Error-Prone Time-Varying Covariates: A Risk Set Calibration Approach, Xiaomei Liao, David M. Zucker, Yi Li, Donna Spiegelman

Harvard University Biostatistics Working Paper Series

No abstract provided.


Evaluating Forensic Dna Evidence, Dan E. Krane Nov 2009

Evaluating Forensic Dna Evidence, Dan E. Krane

Biological Sciences Faculty Publications

No abstract provided.


Modulation Of Outer Hair Cell Electromotility By Cochlear Supporting Cells And Gap Junctions, Ning Yu, Hong-Bo Zhao Nov 2009

Modulation Of Outer Hair Cell Electromotility By Cochlear Supporting Cells And Gap Junctions, Ning Yu, Hong-Bo Zhao

Surgery Faculty Publications

Outer hair cell (OHC) or prestin-based electromotility is an active cochlear amplifier in the mammalian inner ear that can increase hearing sensitivity and frequency selectivity. In situ, Deiters supporting cells are well-coupled by gap junctions and constrain OHCs standing on the basilar membrane. Here, we report that both electrical and mechanical stimulations in Deiters cells (DCs) can modulate OHC electromotility. There was no direct electrical conductance between the DCs and the OHCs. However, depolarization in DCs reduced OHC electromotility associated nonlinear capacitance (NLC) and distortion products. Increase in the turgor pressure of DCs also shifted OHC NLC to the negative …


Analysis Of The Regulation Of The Transferrin Iron Acquisition System In Neisseria Gonorrhoeae, Acevedo Rosuany Vélez Nov 2009

Analysis Of The Regulation Of The Transferrin Iron Acquisition System In Neisseria Gonorrhoeae, Acevedo Rosuany Vélez

Theses and Dissertations

The neisserial transferrin binding proteins (Tbps) comprise a bipartite system for iron acquisition from human transferrin. TbpA is a TonB-dependent outer membrane protein that forms the pore for iron internalization. TbpB is a surface-exposed lipoprotein that makes the iron-uptake process more efficient. Previous studies have shown that the genes encoding these proteins are arranged in a bicistronic operon, with the tbpB gene located upstream of tbpA. The operon is under the control of the ferric uptake regulator (Fur) protein. However, promoter elements necessary for the regulation of the operon have not been experimentally defined. In this study, putative regulatory motifs …


Fall 09 Prescriptions For Excellence Download Full Pdf Nov 2009

Fall 09 Prescriptions For Excellence Download Full Pdf

Prescriptions for Excellence in Health Care Newsletter Supplement

No abstract provided.


Optimization Of Functional Mri Methods For Olfactory Interventional Studies At 3t, Vishwadeep Ahluwalia Nov 2009

Optimization Of Functional Mri Methods For Olfactory Interventional Studies At 3t, Vishwadeep Ahluwalia

Theses and Dissertations

Functional MRI technique is vital in investigating the effect of an intervention on cortical activation in normal and patient population. In many such investigations, block stimulation paradigms are still the preferred method of inducing brain activation during functional imaging sessions because of the high BOLD response, ease in implementation and subject compliance especially in patient population. However, effect of an intervention can be validly interpreted only after reproducibility of a detectable BOLD response evoked by the stimulation paradigm is first verified in the absence of the intervention. Detecting a large BOLD response that is also reproducible is a difficult task …


Brazilian Adolescents Infected By Hiv: Epidemiologic Characteristics And Adherence To Treatment, Julia K. C. Machado, Maria J. C. Sant'anna, Veronica Coates, Flavia J. Almeida, Eitan N. Berezin, Hatim A. Omar Nov 2009

Brazilian Adolescents Infected By Hiv: Epidemiologic Characteristics And Adherence To Treatment, Julia K. C. Machado, Maria J. C. Sant'anna, Veronica Coates, Flavia J. Almeida, Eitan N. Berezin, Hatim A. Omar

Pediatrics Faculty Publications

Over the last 3 decades since the first AIDS cases appeared, we have witnessed great progress in therapeutic methodologies that have transformed the evolution of the disease from debilitating and fatal, into chronic and controllable. HIV-infected children are arriving at adolescence and bringing specific challenges, not only to themselves, but also to their families and caregivers. This retrospective study sets forth epidemiological and treatment characteristics of 46 HIV-infected adolescents followed in a specialized university service relating said characteristics to therapy adherence assessed through a combination of three indirect methods. Therapy adherence did not reveal any association with either epidemiologic characteristics …


Suppression Of Erbb-2 In Androgen-Independent Human Prostate Cancer Cells Enhances Cytotoxic Effect By Gemcitabine In An Androgen-Reduced Environment., Li Zhang, Jeffrey S. Davis, Stanislav Zelivianski, Fen-Fen Lin, Rachel Schutte, Thomas L. Davis, Ralph Hauke, Surinder K. Batra, Ming-Fong Lin Nov 2009

Suppression Of Erbb-2 In Androgen-Independent Human Prostate Cancer Cells Enhances Cytotoxic Effect By Gemcitabine In An Androgen-Reduced Environment., Li Zhang, Jeffrey S. Davis, Stanislav Zelivianski, Fen-Fen Lin, Rachel Schutte, Thomas L. Davis, Ralph Hauke, Surinder K. Batra, Ming-Fong Lin

Journal Articles: Biochemistry & Molecular Biology

We examined the efficacy of combination treatments utilizing cytotoxic drugs plus inhibitors to members of the ErbB-ERK signal pathway in human prostate cancer (PCa) LNCaP C-81 cells. Under an androgen-reduced condition, 50nM gemcitabine caused about 40% growth suppression on C-81 cells. Simultaneous treatment of gemcitabine plus 10microM AG825 produced 60% suppression (p


Quantitative Analysis Of Tobacco Specific Nitrosamine In Human Urine Using Molecularly Imprinted Polymers As A Potential Tool For Cancer Risk Assessment, Kumar Shah Nov 2009

Quantitative Analysis Of Tobacco Specific Nitrosamine In Human Urine Using Molecularly Imprinted Polymers As A Potential Tool For Cancer Risk Assessment, Kumar Shah

Theses and Dissertations

Measuring urinary tobacco specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and its glucuronide conjugate may provide the best biomarker of tobacco smoke lung carcinogen metabolism. Existence of differences in the extent of NNAL metabolism rates may be potentially related to an individuals’ lung cancer susceptibility. Low concentrations of NNAL in smokers urine (<1 ng/mL) require sensitive and selective methods for analysis. Traditionally, this involves extensive, time-consuming sample preparation that limits throughput and adds to measurement variability. Molecularly imprinted polymers (MIPs) have been developed for the analysis of urinary NNAL by offline cartridge extraction combined with LC-MS/MS. This method when reproduced demonstrated problems with matrix effects. In the first part of this work, investigation of matrix effects and related problems with sensitivity for the published offline extraction method has been conducted. In order to address the need to improve throughput and other analytical figures of merit for the original method, the second part of this work deals with development of a high-throughput online microfluidic method using capillary-columns packed with MIP beads for the analysis of urinary NNAL. The method was validated as per the FDA guidance, and enabled low volume, rapid analysis of urinary NNAL by direct injection on a microfluidic column packed with NNAL specific MIP beads. The method was used for analysis of urinary NNAL and NNAL-Gluc in smokers. Chemometric methods were used with this data to develop a potential cancer-risk-assessment tool based on pattern recognition in the concentrations of these compounds in urine. In the last part, method comparison approaches for the online and the offline sample extraction techniques were investigated. A ‘fixed’ range acceptance criterion based on combined considerations of method precision and accuracy, and the FDA bioanalytical guidance limits on precision and accuracy was proposed. Data simulations studies to evaluate the probabilities of successful transfers using the proposed criteria were performed. Various experimental designs were evaluated and a design comprised of 3 runs with 3 replicates each with an acceptance range of ±20% was found appropriate. The off-line and the on-line sample extraction methods for NNAL analysis were found comparable using the proposed fixed range acceptance criteria.