Medicine and Health Sciences Commons^™

Synthesis And Antiproliferative Activities Of Quebecol And Its Analogs, Kasiviswanadharaju Pericherla, Amir Nasrolahi Shirazi, V. Kameshwara Rao, Rakesh Tiwari, Nicholas Dasilva, Kellen Mccaffrey, Yousef A. Beni, Antonio González- Sarrías, Navindra P. Seeram, Keykavous Parang, Anil Kumar

Pharmacy Faculty Articles and Research

Simple and efficient synthesis of quebecol and a number of its analogs was accomplished in five steps. The synthesized compounds were evaluated for antiproliferative activities against human cervix adenocarcinoma (HeLa), human ovarian carcinoma (SK-OV-3), human colon carcinoma (HT-29), and human breast adenocarcinoma (MCF-7) cancer cell lines. Among all the compounds, 7c, 7d, 7f, and 8f exhibited antiproliferative activities against four tested cell lines with inhibition over 80% at 75 mu M after 72 h, whereas, compound 7b and 7g were more selective towards MCF-7 cell line. The IC50 values for compounds 7c, 7d, and 7f were 85.1 mu M, 78.7 …

Tossing The Coin For Half Life, William L. Romine

Biological Sciences Faculty Publications

No abstract provided.

Effects Of Acute Or Chronic Ethanol Exposure During Adolescence On Behavioral Inhibition And Efficiency In A Modified Water Maze Task, Shawn K. Acheson, Craig Bearison, Mary-Louise Risher, Sabri H. Abdelwahab, Wilkie A. Wilson, H. Scott Swartzwelder

Biomedical Sciences

Ethanol is well known to adversely affect frontal executive functioning, which continues to develop throughout adolescence and into young adulthood. This is also a developmental window in which ethanol is misused by a significant number of adolescents. We examined the effects of acute and chronic ethanol exposure during adolescence on behavioral inhibition and efficiency using a modified water maze task. During acquisition, rats were trained to find a stable visible platform onto which they could escape. During the test phase, the stable platform was converted to a visible floating platform (providing no escape) and a new hidden platform was added …

Generating Hypotheses About Care Needs Of High Utilizers: Lessons From Patient Interviews., Dawn B Mautner, Hauchie Pang, Jeffrey C Brenner, Judy A Shea, Kennen S Gross, Rosemary Frasso, Carolyn C Cannuscio

Department of Family & Community Medicine Faculty Papers

Informed by a largely secondary and quantitative literature, efforts to improve care and outcomes for complex patients with high levels of emergency and hospital-based health care utilization have offered mixed results. This qualitative study identifies psychosocial factors and life experiences described by these patients that may be important to their care needs. Semi-structured interviews were conducted with 19 patients of the Camden Coalition of Healthcare Providers' Care Management Team. Investigators coded transcripts using a priori and inductively-derived codes, then identified 3 key themes: (1) Early-life instability and traumas, including parental loss, unstable or violent relationships, and transiency, informed many participants' …

Small Molecule Antagonists Of Melanopsin-Mediated Phototransduction, Kenneth A. Jones, Megumi Hatori, Ludovic S. Mure, Jayne R. Bramley, Roman Artymyshyn, Sang-Phyo Hong, Mohammad Marzabadi, Huailing Zhong, Jeffrey Sprouse, Quansheng Zhu, Andrew T. E. Hartwick, Patricia J. Sollars, Gary E. Pickard, Satchidananda Panda

School of Veterinary and Biomedical Sciences: Faculty Publications

Melanopsin, expressed in a subset of retinal ganglion cells, mediates behavioral adaptation to ambient light and other non-image forming photic responses. This has raised the possibility that pharmacological manipulation of melanopsin can modulate several CNS responses including photophobia, sleep, circadian rhythms and neuroendocrine function. Here we describe the identification of a potent synthetic melanopsin antagonist with in vivo activity. Novel sulfonamide compounds inhibiting melanopsin (opsinamides) compete with retinal binding to melanopsin and inhibit its function without affecting rod/cone mediated responses. In vivo administration of opsinamides to mice specifically and reversibly modified melanopsin-dependent light responses including the pupillary light reflex and …

Jordanian Ethical Perceptions Of Preimplantation Genetic Diagnosis, Sarah C. Miller

Independent Study Project (ISP) Collection

Preimplantation Genetic Diagnosis (PGD) is a procedure that can be done during In Vitro Fertilization (IVF), involving genetic and chromosomal screening of fertilized embryos prior to implantation into a woman’s uterus. After PGD, only the embryos possessing the desired characteristics are implanted, while the other embryos are frozen for future use, or discarded. PGD is used for family balancing (gender selection for balancing the gender dynamic within a family), gender selection to screen out sex-linked diseases, or a broader genetic screening for diseases known to be present in the patient’s family history.

Many ethical questions have been raised about PGD, …

Primary Blast Traumatic Brain Injury In The Rat: Relating Diffusion Tensor Imaging And Behavior, Matthew D. Budde, Alok Shah, Michael Mccrea, William E. Cullinan, Frank A. Pintar, Brian D. Stemper

Biomedical Sciences Faculty Research and Publications

The incidence of traumatic brain injury (TBI) among military personnel is at its highest point in U.S. history. Experimental animal models of blast have provided a wealth of insight into blast injury. The mechanisms of neurotrauma caused by blast, however, are still under debate. Specifically, it is unclear whether the blast shockwave in the absence of head motion is sufficient to induce brain trauma. In this study, the consequences of blast injury were investigated in a rat model of primary blast TBI. Animals were exposed to blast shockwaves with peak reflected overpressures of either 100 or 450 kPa (39 and …

High Dose, Variable Length, N-Acetylcysteine (Hinac) Therapy For Late-Presenting Acetaminophen Poisoning, Jessica K. Eygnor Do, Suprina Dorai Md, Philip W. Moore Do, J Ward Donovan Md, Keith K. Burkhart Md

Department of Emergency Medicine

No abstract provided.

Mapping The Knowledge Economy Of Medicinal Plants In Northern Madagascar: Information And Resource Flow In Traditional Health Practices, Chanelle Adams

Independent Study Project (ISP) Collection

In the wake of pharmaceutical success with alkaloid compounds found in the Madagascar periwinkle (Catharanthus roseus), there has been increased attention towards identifying medicinal properties in the country’s rich flora. Both native and foreign companies seek profitable use of wild plant species found within Madagascar’s unique biodiversity. Many conservation organizations believe that the world’s forests in biological “hot spots” contain cures unknown to modern science and therefore, their preservation essential.

While the protection of these natural resources is important to Western medicine, it is even more vital for local people who depend on the forest as their primary …

Patient Communication In Radiology: Current Status Of Breaking Bad News Among Radiologists And Radiology Trainees In Pakistan, Ranish Deedar Ali Khawaja, Waseem Akhtar, Ali Khawaja, Hira Irfan, Mohammad Naeem, Mukhtiar Memon

Medical College Documents

Breaking bad news can be an intimidating task for any physician. The aim of this study was to record the practices of breaking bad news to the patients by Pakistani radiologists and trainees. The radiologists and trainees attending the 26th National Radiological Conference in October 2010 in Karachi, Pakistan, were surveyed. The response rate was 76%. The respondents included residents (51%), private practicing radiologists (28%), academic radiologists (13%), and other trainees (8%). Most of the academic radiologists communicated with their patients. The daily frequency of breaking bad news by residents was noted, which was highest in the public teaching hospitals …

A Miniaturised Spectrometer Device For The Detection Of Nitrogen Dioxide In An Urban Environment, Brian Devine

Doctoral

Monitoring of air pollutants, such as Nitrogen Dioxide (NO2), that are toxic or environmentally damaging is a key metric for environmental protection agencies worldwide. There is a constant need to develop new technologies and methodologies that provide real-time, low cost pollution measurements over a broad range of sampling sites, particularly in urban and industrial areas. Typically, detection of pollutants in urban environments is performed using a variety of techniques, many of which are expensive, require complex setups and are in fixed locations. The novel system presented in this thesis is designed for portable, low cost and in-situ detection of pollutants …

Prostate Cancer Stem Cell-Targeted Efficacy Of A New-Generation Taxoid, Sbt-1214 And Novel Polyenolic Zinc-Binding Curcuminoid, Cmc2.24, Galina I. Botchkina, Edison S. Zuniga, Rebecca H. Rowehl, Rosa Park, Rahuldev Bhalla, Agnieszka B. Bialkowska, Francis Johnson, Lorne M. Golbu, Yu Zhang, Iwao Ojima, Kenneth R. Shroyer

Department of Biomedical Engineering Faculty Publications

Background

Prostate cancer is the second leading cause of cancer death among men. Multiple evidence suggests that a population of tumor-initiating, or cancer stem cells (CSCs) is responsible for cancer development and exceptional drug resistance, representing a highly important therapeutic target. The present study evaluated CSC-specific alterations induced by new-generation taxoid SBT-1214 and a novel polyenolic zinc-binding curcuminoid, CMC2.24, in prostate CSCs.

Principal Findings

The CD133high/CD44high phenotype was isolated from spontaneously immortalized patient-derived PPT2 cells and highly metastatic PC3MM2 cells. Weekly treatment of the NOD/SCID mice bearing PPT2- and PC3MM3-induced tumors with the SBT-1214 led to dramatic suppression of tumor …

Scavenger Receptor Class B Type I Regulates Cellular Cholesterol Metabolism And Cell Signaling Associated With Breast Cancer Development., Christiane Danilo, Jorge L Gutierrez-Pajares, Maria Antonietta Mainieri, Isabelle Mercier, Michael P. Lisanti, Philippe G. Frank

Department of Stem Cell Biology and Regenerative Medicine Faculty Papers & Presentations

INTRODUCTION: Previous studies have identified cholesterol as an important regulator of breast cancer development. High-density lipoprotein (HDL) and its cellular receptor, scavenger receptor class B type I (SR-BI) have both been implicated in the regulation of cellular cholesterol homeostasis, but their functions in cancer remain to be established.

METHODS: In the present study, we have examined the role of HDL and SR-BI in the regulation of cellular signaling pathways in breast cancer cell lines and in the development of tumor in a mouse xenograft model.

RESULTS: Our data show that HDL is capable of stimulating migration and can activate signal …

Proteomic Analysis Of Mismatch Repair-Mediated Alkylating Agent-Induced Dna Damage Response, Xi Chen, Yong Zhao, Guo-Min Li, Lin Guo

Toxicology and Cancer Biology Faculty Publications

BACKGROUND: Mediating DNA damage-induced apoptosis is an important genome-maintenance function of the mismatch repair (MMR) system. Defects in MMR not only cause carcinogenesis, but also render cancer cells highly resistant to chemotherapeutics, including alkylating agents. To understand the mechanisms of MMR-mediated apoptosis and MMR-deficiency-caused drug resistance, we analyze a model alkylating agent (N-methyl-N’-nitro-N-nitrosoguanidine, MNNG)-induced changes in protein phosphorylation and abundance in two cell lines, the MMR-proficient TK6 and its derivative MMR-deficient MT1.

RESULTS: Under an experimental condition that MNNG-induced apoptosis was only observed in MutSα-proficient (TK6), but not in MutSα-deficient (MT1) cells, quantitative analysis …

A Standardized Patient Counseling Rubric For A Pharmaceutical Care And Communications Course, Niambi Horton Pharmd, Kenna D. Payne Pharmd, Michelle Jernigan Pharmd, Jill Frost Pharmd, Stephen Wise Pharmd, Mary Klein Pharmd, Joel Epps Mba, H. Glenn Anderson Pharmd

Pharmaceutical Science and Research

Objective. To restructure a required pharmaceutical care and communications course to place greater emphasis on communication skills and include a high-stakes assessment.

Design. A standardized counseling rubric was developed for use throughout the pharmacy curriculum and the counseling laboratory practicals were changed to high-stakes assessments.

Assessment. An annual mid-semester and end-of-semester high-stakes patient-counseling objective structured clinical examination (OSCE) conducted prior to and after revision of the course and counseling rubric documented improvements in students’ scores. Performance on the post-course annual assessment patient counseling OSCE improved compared to that on the pre-course (p,0.001).

Conclusion. The 2010 course revision improved …

Cholinergic Enhancement Of Brain Activation In Mild Cognitive Impairment During Episodic Memory Encoding, Shannon L. Risacher, Yang Wang, Heather A. Wishart, Laura A. Rabin, Laura A. Flashman, Brenna C. Mcdonald, John D. West, Robert B. Santulli, Andrew J. Saykin

Publications and Research

Objective: To determine the physiological impact of treatment with donepezil (Aricept) on neural circuitry supporting episodic memory encoding in patients with amnestic mild cognitive impairment (MCI) using functional magnetic resonance imaging (fMRI).

Methods: Eighteen patients with MCI and 20 age-matched healthy controls (HC) were scanned twice while performing an event-related verbal episodic encoding task. MCI participants were scanned before treatment and after approximately 3 months on donepezil; HCwere untreated but rescanned at the same interval.Voxel-level analyses assessed treatment effects on activation profiles in MCI patients relative to retest changes in non-treated HC. Changes in task-related connectivity in medial temporal circuitry …

De Novo Frameshift Mutation In Asxl3 In A Patient With Global Developmental Delay, Microcephaly, And Craniofacial Anomalies., Darrell L. Dinwiddie, Sarah E. Soden, Carol J. Saunders, Neil A. Miller, Emily G. Farrow, Laurie D. Smith, Stephen F. Kingsmore

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Currently, diagnosis of affected individuals with rare genetic disorders can be lengthy and costly, resulting in a diagnostic odyssey and in many patients a definitive molecular diagnosis is never achieved despite extensive clinical investigation. The recent advent and use of genomic medicine has resulted in a paradigm shift in the clinical molecular genetics of rare diseases and has provided insight into the causes of numerous rare genetic conditions. In particular, whole exome and genome sequencing of families has been particularly useful in discovering de novo germline mutations as the cause of both rare diseases and complex disorders.

CASE PRESENTATION: …

Transient And Selective Suppression Of Neural Activity With Infrared Light, Michael W. Jenkins, Hui Lu, Jeffrey M. Mcmanus, Hillel J. Chiel

Faculty Scholarship

Analysis and control of neural circuitry requires the ability to selectively activate or inhibit neurons. Previous work showed that infrared laser light selectively excited neural activity in endogenous unmyelinated and myelinated axons. However, inhibition of neuronal firing with infrared light was only observed in limited cases, is not well understood and was not precisely controlled. Using an experimentally tractable unmyelinated preparation for detailed investigation and a myelinated preparation for validation, we report that it is possible to selectively and transiently inhibit electrically- initiated axonal activation, as well as to both block or enhance the propagation of action potentials of specific …

The Role Of Nitric Oxide Dysregulation In Tumor Maintenance, Christopher Rabender

Theses and Dissertations

The inflammatory nature of the tumor microenvironment provides a cytokine and chemokine rich proliferative environment. Much of the responsibility of this environment is due to the production of Reactive Oxygen Species (ROS). These studies examined the proliferative rich tumor environment from a new perspective of Nitric Oxide Synthase (NOS) dysregulation. NOS’s have the ability to become uncoupled and generate superoxide in lieu of nitric oxide (NO). A requirement of NOS for the production of NO is the cofactor tetrahydrobiopterin (BH4) and when it is missing NOS becomes uncoupled and turns into a peroxynitrite synthase. Here I demonstrate that NOS is …

How Studies Of Human Sex Ratios At Birth May Lead To The Understanding Of Several Forms Of Pathology, William H. James

Human Biology Open Access Pre-Prints

This paper deals with the problem of the causes of the variation of sex ratio (proportion male) at birth. This problem is common to a number of areas in biology and medicine e.g. obstetrics, neurology/psychiatry, parasitology, virology, oncology and teratology. It is established that there are significantly biased, but unexplained, sex ratios in each of these fields. Yet workers in them (with the possible exception of virology) have regarded the problem as a minor loose end, irrelevant to the field’s major problems. However, as far as I know, no-one has previously noted that unexplained biased sex ratios occur, and thus …

Aspirin And Low-Molecular Weight Heparin Combination Therapy Effectively Prevents Recurrent Miscarriage In Hyperhomocysteinemic Women., Pratip Chakraborty, Sayani Banerjee, Piyali Saha, Shyam Sundar Nandi, Sunita Sharma, Sourendra K. Goswami, Baidyanath Chakravarty, Syed N. Kabir

Journal Articles: Cellular & Integrative Physiology

The management of recurrent pregnancy loss (RPL) still remains a great challenge, and women with polycystic ovarian syndrome (PCOS) are at a greater risk for spontaneous abortion. Treatment with low-molecular-weight heparin (LMWH) has become an accepted treatment option for women with RPL; however, the subgroup of women, who are likely to respond to LMWH, has not been precisely identified. The present study evaluated the efficacy of LMWH with reference to PCOS and associated metabolic phenotypes including hyperhomocysteinemia (HHcy), insulin resistance (IR) and obesity. This prospective observational study was conducted at Institute of Reproductive Medicine, Kolkata, India. A total of 967 …

Combined Fluorescent In Situ Hybridization For Detection Of Micrornas And Immunofluorescent Labeling For Cell-Type Markers, Amrita Datta Chaudhuri, Sowmya V. Yelamanchili, Howard S. Fox

Journal Articles: Pharmacology & Experimental Neuroscience

Identification of the cell type of origin for normal or aberrant gene expression is critical for many studies, and poses a significant problem for some regulatory RNAs such as microRNAs. MicroRNAs are small non-coding RNAs that regulate cellular function by targeting specific mRNAs and reducing the level of their protein product. Aberrant expression of miRNAs in cell-types where they are not normally expressed occurs in several disease conditions. Therefore, it is important to determine not only the expression level of microRNAs, but also where they are expressed. Here we describe a detailed method for fluorescent in situ hybridization (FISH) combined …

The Science (And Pseudoscience) Of Dna Profiling, Dan E. Krane

Biological Sciences Faculty Publications

No abstract provided.

Nf1 Loss And Ras Hyperactivation In Oligodendrocytes Induce Nos-Driven Defects In Myelin And Vasculature, Debra A. Mayes, Tilat A. Rizvi, Haley E. Titus-Mitchell, Rachel Oberst, Georgianne M. Ciraolo, Charles V. Vorhees, Andrew P. Robinson, Stephen D. Miller, Jose A. Cancelas, Anat O. Stemmer-Rachamimov, Nancy Ratner

Neuroscience, Cell Biology & Physiology Faculty Publications

Patients with neurofibromatosis type 1 (NF1) and Costello syndrome Rasopathy have behavioral deficits. In NF1 patients, these may correlate with white matter enlargement and aberrant myelin. To model these features, we induced Nf1 loss or HRas hyperactivation in mouse oligodendrocytes. Enlarged brain white matter tracts correlated with myelin decompaction, downregulation of claudin-11, and mislocalization of connexin-32. Surprisingly, non-cell-autonomous defects in perivascular astrocytes and the blood-brain barrier (BBB) developed, implicating a soluble mediator. Nitric oxide (NO) can disrupt tight junctions and gap junctions, and NO and NO synthases (NOS1-NOS3) were upregulated in mutant white matter. Treating mice with the NOS inhibitor …

Trigeminal Trophic Syndrome, Ryan Owen Do, Joshua M. Levin Md, Stephen M. Purcell Do

Department of Medicine

No abstract provided.

Reactive Hyperemia Occurs Via Activation Of Inwardly Rectifying Potassium Channels And Na+/K+-Atpase In Humans, Anne R. Crecelius, Jennifer C. Richards, Gary J. Luckasen, Dennis G. Larson, Frank A. Dinenno

Health and Sport Science Faculty Publications

Rationale: Reactive hyperemia (RH) in the forearm circulation is an important marker of cardiovascular health, yet the underlying vasodilator signaling pathways are controversial and thus remain unclear.

Objective: We hypothesized that RH occurs via activation of inwardly rectifying potassium (K_IR) channels and Na⁺/K⁺-ATPase and is largely independent of the combined production of the endothelial autocoids nitric oxide (NO) and prostaglandins in young healthy humans.

Methods and Results: In 24 (23±1 years) subjects, we performed RH trials by measuring forearm blood flow (FBF; venous occlusion plethysmography) after 5 minutes of arterial occlusion. In protocol 1, …

Structure, Theoretical Studies And Coupling Reactions Of Some New Cyclic Boronic Esters, Andrew Kuttler, Sravanthi Durganala, Albert Fratini, Alexander Morgan, Vladimir Benin

Chemistry Faculty Publications

The present report describes the X-ray structural and theoretical studies of some new pinacolboronate esters, and it also outlines the use of the target structures in Suzuki coupling reactions to produce new aromatic or heteroaromatic esters and amides. X-ray structural analysis of the studied compounds revealed that the pinacolborane ring's position with respect to the benzene ring varies, depending on the particular environment. An ortho-positioned carboxylic ester (methyl ester) causes a nearly perpendicular orientation of the pinacolborane unit with respect to the benzene ring, whereas an ortho-positioned amide (N,N-dimethylamide) causes the pinacolborane unit to orient itself nearly coplanar. A plausible …

Successful Long-Term Extracorporeal Cardiopulmonary Membrane Oxygenation Without Anti-Coagulation, Janissa Nair, Dorothea T. Watson Do, Rita Pechulis Md, Fccp, Nicholas M. Rini Pa-C, Timothy S. Misselbeck, Kenneth Miller Rrt, James K. Wu Md

Department of Surgery

No abstract provided.

Maternal Genital Tract Colonisation By Group-B Streptococcus: A Hospital Based Study, Nida Najmi, Rozina Sikandar, Nadeem F. Zuberi, Imtiaz Jehan

Department of Obstetrics & Gynaecology

Objectives: To determine the prevalence of Group B Streptococcus genital tract infection in pregnant women and to determine the risk factors for its colonisation.
Methods: The cross-sectional study was conducted at the Aga Khan University Hospital, Karachi and Sobhraj Hospital, Karachi, from May to August 2007. Pregnant women at 35-37 weeks gestation attending antenatal clinic at these hospitals constituted the study population. Based on stratified sampling, 405 patients were recruited. High vaginal swabs of these patients were taken in order to calculate the prevalence of infection at each hospital. Logistic regression was used to evaluate the risk factor association. SPSS …

Role Of Vimf In Gingipain Maturation In Porphyromonas Gingivalis, Arun S. Muthiah

Loma Linda University Electronic Theses, Dissertations & Projects

Gingipain activity in Porphyromonas gingivalis, the major etiological agent in adult periodontitis, is post-translationally regulated by unique Vim proteins including VimF, a putative glycosyltransferase. To ascertain the VimF mediated phenotype we first inactivated the vimF gene in P. gingivalis ATCC 33277 (FLL476), a less virulent fimbriated strain. We observed that the vimF-defective mutant (FLL476) showed a phenotype similar to that of the vimF-defective mutant (FLL95) in the P. gingivalis W83 background. While hemagglutination was not detected and autoaggregationn was reduced, biofilm formation was increased in FLL476. Also, invasive capacity decreased for this mutant. Furthermore, fimbrial structures were missing in FLL476, …