Digital Commons Network^™

Primers And Probe To Identify Mycobacterium Tuberculosis Complex, Subodh M. Lele, Manjiri S. Lele, Nada H. Khattar

Pathology and Laboratory Medicine Faculty Patents

Methods and nucleic acids for rapid, reliable and sensitive detection of Mycobacterium tuberculosis (MTB) complex pathogen in a biological sample. Oligonucleotides are provided which amplify MTB DNA and which are useful in carrying out real time PCR of DNA obtained from formalin-fixed and paraffin-embedded tissue samples.

Novel Role Of Antioxidant-1 (Atox1) As A Copper-Dependent Transcription Factor Involved In Cell Proliferation, S. Itoh, H. W. Kim, O. Nakagawa, K. Ozumi, Susan M. Lessner, H. Aoki, K. Akram, R. D. Mckinney, M. Ushio-Fukai, T. Fukai

Faculty Publications

Copper plays a fundamental role in regulating cell growth. Many types of human cancer tissues have higher copper levels than normal tissues. Copper can also induce gene expression. However, transcription factors that mediate copper-induced cell proliferation have not been identified in mammals. Here we show that antioxidant-1 (Atox1), previously appreciated as a copper chaperone, represents a novel copper-dependent transcription factor that mediates copper-induced cell proliferation. Stimulation of mouse embryonic fibroblasts (MEFs) with copper markedly increased cell proliferation, cyclin D1 expression, and entry into S phase, which were completely abolished in Atox1^-/- MEFs. Promoter analysis and EMSA revealed that copper …

Diabetes Alters Contraction-Induced Mitogen Activated Protein Kinase Activation In The Rat Soleus And Plantaris, Anjaiah Katta, Deborah L. Preston, Sunil K. Kakarla, Shinichi Asano, Sarath Meduru, Sriram P. Mupparaju, Ellie Yokochi, Kevin M. Rice, Devashish H. Desai, Eric R. Blough

MIIR Faculty Research

The prescription of anaerobic exercise has recently been advocated for the management of diabetes; however exercise-induced signaling in diabetic muscle remains largely unexplored. Evidence from exercise studies in nondiabetics suggests that the extracellular-signal-regulated kinases (Erk1/2), p38, and c-JUN NH2-terminal kinase (Jnk) mitogen-activated protein kinases (MAPKs) are important regulators of muscle adaptation. Here, we compare the basal and the in situ contraction-induced phosphorylation of Erk1/2- p38- and Jnk-MAPK and their downstream targets (p90rsk and MAPKAP-K2) in the plantaris and soleus muscles of normal and obese (fa/fa) Zucker rats. Compared to lean animals, the time course and magnitude of Erk1/2, p90rsk and …

Abeta42 Mutants With Different Aggregation Profiles Induce Distinct Pathologies In Drosophila., Koichi Iijima, Hsueh-Cheng Chiang, Stephen A Hearn, Inessa Hakker, Anthony Gatt, Christopher Shenton, Linda Granger, Amy Leung, Kanae Iijima-Ando, Yi Zhong

Department of Biochemistry and Molecular Biology Faculty Papers

Aggregation of the amyloid-beta-42 (Abeta42) peptide in the brain parenchyma is a pathological hallmark of Alzheimer's disease (AD), and the prevention of Abeta aggregation has been proposed as a therapeutic intervention in AD. However, recent reports indicate that Abeta can form several different prefibrillar and fibrillar aggregates and that each aggregate may confer different pathogenic effects, suggesting that manipulation of Abeta42 aggregation may not only quantitatively but also qualitatively modify brain pathology. Here, we compare the pathogenicity of human Abeta42 mutants with differing tendencies to aggregate. We examined the aggregation-prone, EOFAD-related Arctic mutation (Abeta42Arc) and an artificial mutation (Abeta42art) that …

Fibulin-2 Is Dispensable For Mouse Development And Elastic Fiber Formation, Francois-Xavier Sicot, Takeshi Tsuda, Dessislava Markova, John Klement, Machiko Arita, Rui-Zhu Zhang, Te-Cheng Pan, Robert P. Mecham, David E. Birk, Mon-Li Chu

Department of Dermatology and Cutaneous Biology Faculty Papers

Fibulin-2 is an extracellular matrix protein belonging to the five-member fibulin family, of which two members have been shown to play essential roles in elastic fiber formation during development. Fibulin-2 interacts with two major constituents of elastic fibers, tropoelastin and fibrillin-1, in vitro and localizes to elastic fibers in many tissues in vivo. The protein is prominently expressed during morphogenesis of the heart and aortic arch vessels and at early stages of cartilage development. To examine its role in vivo, we generated mice that do not express the fibulin-2 gene (Fbln2) through homologous recombination of embryonic stem cells. Unexpectedly, the …

Trk: A Neuromodulator Of Age-Specific Behavioral And Neurochemical Responses To Cocaine In Mice., Michelle Niculescu, Shane A Perrine, Jonathan S Miller, Michelle E Ehrlich, Ellen M Unterwald

Farber Institute for Neuroscience Faculty Papers

Responses to psychostimulants vary with age, but the molecular etiologies of these differences are largely unknown. The goal of the present research was to identify age-specific behavioral and molecular adaptations to cocaine and to elucidate the mechanisms involved therein. Postweanling, periadolescent, and adult male CD-1 mice were exposed to cocaine (20 mg/kg) for 7 d. The rewarding effects of cocaine were assessed, as were the response to a Trk antagonist and the regulation of dopamine and cAMP-regulated phosphoprotein, 32 kDa (DARPP-32). Cocaine was rewarding in both periadolescent and adult mice using a conditioned place preference procedure. In contrast, postweanling mice …

The Expression Of Microrna Mir-107 Decreases Early In Alzheimer's Disease And May Accelerate Disease Progression Through Regulation Of Β-Site Amyloid Precursor Protein-Cleaving Enzyme 1, Wang-Xia Wang, Bernard W. Rajeev, Arnold J. Stromberg, Na Ren, Guiliang Tang, Qingwei Huang, Isidore Rigoutsos, Peter T. Nelson

Sanders-Brown Center on Aging Faculty Publications

MicroRNAs (miRNAs) are small regulatory RNAs that participate in posttranscriptional gene regulation in a sequence-specific manner. However, little is understood about the role(s) of miRNAs in Alzheimer's disease (AD). We used miRNA expression microarrays on RNA extracted from human brain tissue from the University of Kentucky Alzheimer's Disease Center Brain Bank with near-optimal clinicopathological correlation. Cases were separated into four groups: elderly nondemented with negligible AD-type pathology, nondemented with incipient AD pathology, mild cognitive impairment (MCI) with moderate AD pathology, and AD. Among the AD-related miRNA expression changes, miR-107 was exceptional because miR-107 levels decreased significantly even in patients with …

Diverse Antidepressants Increase Cdp-Diacylglycerol Production And Phosphatidylinositide Resynthesis In Depression-Relevant Regions Of The Rat Brain, Kimberly R. Tyeryar, Habiba O.U. Vongtau, Ashiwel S. Undieh

College of Pharmacy Faculty Papers

BACKGROUND: Major depression is a serious mood disorder affecting millions of adults and children worldwide. While the etiopathology of depression remains obscure, antidepressant medications increase synaptic levels of monoamine neurotransmitters in brain regions associated with the disease. Monoamine transmitters activate multiple signaling cascades some of which have been investigated as potential mediators of depression or antidepressant drug action. However, the diacylglycerol arm of phosphoinositide signaling cascades has not been systematically investigated, even though downstream targets of this cascade have been implicated in depression. With the ultimate goal of uncovering the primary postsynaptic actions that may initiate cellular antidepressive signaling, we …

In Vitro Analysis Of Tobramycin-Treated Pseudomonas Aeruginosa Biofilms On Cystic Fibrosis-Derived Airway Epithelial Cells, Gregory G. Anderson, Sophie Moreau-Marquis, Bruce A. Stanton, George A. O'Toole

Dartmouth Scholarship

P. aeruginosa forms biofilms in the lungs of individuals with cystic fibrosis (CF); however, there have been no effective model systems for studying biofilm formation in the CF lung. We have developed a tissue culture system for growth of P. aeruginosa biofilms on CF-derived human airway cells that promotes the formation of highly antibiotic-resistant microcolonies, which produce an extracellular polysaccharide matrix and require the known abiotic biofilm formation genes flgK and pilB. Treatment of P. aeruginosa biofilms with tobramycin reduced the virulence of the biofilms both by reducing bacterial numbers and by altering virulence gene expression. We performed microarray analysis …

Gene Expression Profile Of Neuronal Progenitor Cells Derived From Hescs: Activation Of Chromosome 11p15.5 And Comparison To Human Dopaminergic Neurons., William J Freed, Jia Chen, Cristina M Bäckman, Catherine M Schwartz, Tandis Vazin, Jingli Cai, Charles E Spivak, Carl R Lupica, Mahendra S Rao, Xianmin Zeng

Farber Institute for Neuroscience Faculty Papers

BACKGROUND: We initiated differentiation of human embryonic stem cells (hESCs) into dopamine neurons, obtained a purified population of neuronal precursor cells by cell sorting, and determined patterns of gene transcription.

METHODOLOGY: Dopaminergic differentiation of hESCs was initiated by culturing hESCs with a feeder layer of PA6 cells. Differentiating cells were then sorted to obtain a pure population of PSA-NCAM-expressing neuronal precursors, which were then analyzed for gene expression using Massive Parallel Signature Sequencing (MPSS). Individual genes as well as regions of the genome which were activated were determined.

PRINCIPAL FINDINGS: A number of genes known to be involved in the …

Repression Of Hla By Rot Is Dependent On Sae In Staphylococcus Aureus, Dongmei Li, Ambrose Cheung

Dartmouth Scholarship

The regulatory locus sae is a two-component system in Staphylococcus aureus that regulates many important virulence factors, including alpha-toxin (encoded by hla) at the transcriptional level. The SarA homologs Rot and SarT were previously shown to be repressors of hla in selected S. aureus backgrounds. To delineate the interaction of rot and sae and the contribution of sarT to hla expression, an assortment of rot and sae isogenic single mutants, a rot sae double mutant, and a rot sae sarT markerless triple mutant were constructed from wild-type strain COL. Using Northern blot analysis and transcriptional reporter gene green fluorescent protein, …

Morphine Exacerbates Hiv-1 Tat-Induced Cytokine Production In Astrocytes Through Convergent Effects On [Ca2+]I, Nf-Κb Trafficking And Transcription, Nazira El-Hage, Annadora J. Bruce-Keller, Tatiana Yakovleva, Igor Bazov, Georgy Bakalkin, Pamela E. Knapp, Kurt F. Hauser

Pharmacology and Toxicology Publications

Astroglia are key cellular sites where opiate drug signals converge with the proinflammatory effects of HIV-1 Tat signals to exacerbate HIV encephalitis. Despite this understanding, the molecular sites of convergence driving opiate-accelerated neuropathogenesis have not been deciphered. We therefore explored potential points of interaction between the signaling pathways initiated by HIV-1 Tat and opioids in striatal astrocytes. Profiling studies screening 152 transcription factors indicated that the nuclear factor-kappa B (NF-κB) subunit, c-Rel, was a likely candidate for Tat or Tat plus opiate-induced increases in cytokine and chemokine production by astrocytes. Pretreatment with the NF-κB inhibitor parthenolide provided evidence that Tat±morphine-induced …

Long Lasting Synchronization Of Calcium Oscillations By Cholinergic Stimulation In Isolated Pancreatic Islets, Min Zhang, Bernard Fendler, Bradford Peercy, Pranay Goel, Richard Bertram, Arthur Sherman, Leslie Satin

Pharmacology and Toxicology Publications

Abstract

Individual mouse pancreatic islets exhibit oscillations in [Ca²⁺]_i and insulin secretion in response to glucose in vitro, but how the oscillations of a million islets are coordinated within the human pancreas in vivo is unclear. Islet to islet synchronization is necessary, however, for the pancreas to produce regular pulses of insulin. To determine whether neurohormone release within the pancreas might play a role in coordinating islet activity, [Ca²⁺]_i changes in 4–6 isolated mouse islets were simultaneously monitored before and after a transient pulse of a putative synchronizing agent. The degree of synchronicity was …

Book Review: Drugs During Pregnancy And Lactation: Treatment Options And Risk Assessment, Robert L. Brent

The Selected Works of Robert Brent

No abstract provided.

Effects Of Aging And Gender On Regulators Of Muscle Adaptation In F344/Bn Rat Model, Satyanarayana Paturi

Theses, Dissertations and Capstones

Sarcopenia is the loss of muscle mass and strength that occurs with aging. Here we examine the effects of aging and gender on the regulation of molecules believed to regulate muscle growth and adaptation in the F344/BN rat. In male animals, soleus and EDL muscle/body weight ratio declined continuously with aging while muscle atrophy in female animals plateaued at 26-months and remained constant thereafter. Aging increased the phosphorylation of protein kinase-B (Akt) and the mammalian target of rapamycin (mTOR) in the female but not male soleus muscle. This finding was associated with the attenuation of muscle atrophy observed in female …

Manganese Superoxide Dismutase Contributes To Cisplatin-Induced Cytotoxicity Rather Than All-Trans Retinoic Acid-Dependent Chemoresistance, Zina-Ann Cardozo

Theses, Dissertations and Capstones

Neuroblastoma is an extra-cranial solid tumor of the nervous system occurring predominantly in infants and children younger than five years of age. Neuroblastoma presents a challenge to therapy primarily due to a decreased responsiveness to anticancer agents like cisplatin (CDDP), leading to recurrence. Vitamin A and its derivatives, known as retinoids, are preventive against cancer and induce differentiation in some cell lines. Retinoids are now being tested clinically for the treatment of neuroblastoma. One major limitation to retinoid therapy is the development of chemoresistance. In the present study human SK-N-SH neuroblastoma cells pretreated with 10 μM all-trans retinoic acid (ATRA) …

Impaired Overload-Induced Hypertrophy In Obese Zucker Rat Slow-Twitch Skeletal Muscle, Anil Kumar Gutta

Theses, Dissertations and Capstones

How insulin resistant muscle responds to mechanical overload (MOV) is not well understood. Using immunohistochemical analysis and immunoblotting, we investigated whether Lean Zucker (LZ) and insulin resistant Obese Zucker rats (OZ) respond in a similar fashion to MOV. Five young adult (2 months old) male LZ and OZ rats were subjected to a surgical ablation of the gastrocnemius muscle and overloaded for 8 weeks. MOV-induced increases in soleus muscle mass and average fiber cross-sectional area were attenuated in OZ compared to LZ animals. This reduction in OZ muscle adaptation was associated with decreased activity / phosphorylation levels of STAT3, β-catenin …

Fusion, 2008, George Washington University, William H. Beaumont Medical Research Honor Society

Fusion

No abstract provided.

Attenuation Of Vasospasm By Dexmedetomidine After Experimental Subarachnoidal Haemorrhage In Rabbits, Olcay Eser, Hüseyi̇n Fi̇dan, Ömer Çoşkun, Yüksel Ela, Ahmet Songur, Murat Coşar

Turkish Journal of Medical Sciences

Aim: Vasospasm is one of the most important factors that influence the successful treatment of ruptured intracranial aneurysm. We studied if vasospasm following subarachnoidal haemorrhage (SAH) can be alleviated by dexmedetomidine in an animal model. Materials and Methods: Experimental SAH was induced in 12 of 18 New Zealand rabbits by intracisternal injection of autologous blood. Control animals (sham SAH, n = 6) received intracisternal injection of the respective volume of physiological saline solution. Forty eight hours after the operation, rabbits in sham SAH and SAH-alone (n = 6) groups were infused intravenously with 0.9% sodium chloride for 2 h, whereas …

The Effect Of Caffeic Acid Phenethyl Ester (Cape) Treatment On Levels Of Mda, No And Antioxidant Enzyme Activities In Retinas Of Streptozotocin-Induced Diabetic Rats, Mustafa Durmuş, H. Ramazan Yilmaz, Efkan Uz, Nurten Özçeli̇k

Turkish Journal of Medical Sciences

Aim: This study was performed to determine the effect of caffeic acid phenethyl ester (CAPE) treatment on levels of malondialdehyde (MDA) and nitric oxide (NO) and activities of antioxidant enzymes in retinas of streptozotocin (STZ)-induced diabetic rats. Materials and Methods: Twenty-seven rats were enrolled and divided into three groups: group 1: non-diabetic rats as control (n = 9); group 2: STZ-induced, untreated diabetic rats (n = 8); and group 3: STZ-induced, CAPE-treated diabetic rats (n = 10). Levels of MDA and NO and the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in retinal tissues were analyzed. Results: In …

Current Trends And Future Implications In Sepsis Treatment, Bariş Doğu Yildiz, Kaya Yorganci

Turkish Journal of Medical Sciences

Sepsis is a systemic illness caused by invasion of tissues by pathogens. It is highly lethal, causing circulatory failure and death. There has been extensive research trying to identify possible therapies for sepsis. Apart from source control, and antibiotic and supportive therapy, glucocorticoids, anticoagulant agents, and immunoglobulins have been tried in both the experimental setting and in septic patients. Newer strategies include novel anticoagulant agents like ethyl pyruvate, statins, insulin receptor modulators and Toll-like receptor modulators. This review article summarizes both the current therapies and endeavors for future treatment in sepsis.

Oropharyngeal Anthrax, Abdullah Taş, Recep Yağiz, Şaban Gürcan, Deni̇z Karaoğlu

Turkish Journal of Medical Sciences

Aims: To report a rare case of oropharyngeal anthrax. Materials and Methods: A case report of oropharyngeal anthrax is presented together with the related world literature. Results: A 70-year-old female patient with respiratory distress and extensive swelling of neck, soft palate and uvula is presented. There was ecchymosis on the neck circumferentially. Bacillus anthracis grew in the blood culture. The patient died of toxemia and sepsis. Conclusions: Oropharyngeal anthrax is the least common form of anthrax. This acute illness should be added to the differential diagnosis of inflammatory lesion of the oropharynx with extensive neck swelling. Successful diagnosis of anthrax …

Environmental Causes Of Human Congenital Malformations: The Physician's Role In Dealing With These Complex Clinical Problems Caused By Environmental And Genetic Factors., Robert L. Brent

The Selected Works of Robert Brent

No abstract provided.

Forensic Emergency Medicine - Six-Year Experience Of 13823 Cases In A University Emergency Department, Ahmet Demi̇rcan, Ayfer Keleş, Nesli̇han Gürbüz, Fi̇kret Bi̇ldi̇k, Şahender Gülbi̇n Aygencel, Nuretti̇n Özgür Doğan, Okşan Deri̇nöz, Taner Akar

Turkish Journal of Medical Sciences

Aims: Clinical forensic medicine deals with cases involving both the legal and medical aspects of patient care, such as motor vehicle trauma or poisoning. In this study, we aimed to draw attention to the forensic issues by retrospective investigation of 13823 emergency cases and to share our experiences on this topic. Materials and Methods: This retrospective study was conducted in a university Emergency Department (ED) in Ankara, Turkey. The data were collected from official hospital police sheets. Results: Between 2000 and 2005, 13823 legal cases (3.66% of all ED patients) were examined, and 58.23% of them were male. The mean …

Association Of Epstein-Barr Virus With Nasopharyngeal Carcinoma And Current Status Of Development Of Cancer-Derived Cell Lines, Charles A. Gullo Phd, Wong Kein Low, Gerrard Teoh

Biochemistry and Microbiology

It is well known that the Epstein-Barr virus (EBV) contributes directly to tumourigenesis in nasopharyngeal carcinoma (NPC), primarily in the undifferentiated form of NPC (WHO type III; UNPC or UC), which is commonly found in South East Asia. Unfortunately, research in NPC has been severely hampered by the lack of authentic EBV-positive (EBV+) human NPC cell lines for study. Since 1975, there have been more than 20 reported NPC cell lines. However, many of these NPC-derived cell lines do not express EBV transcripts in long-term culture, and therefore that finding may dispute the fundamental theory of NPC carcinogenesis. In fact, …

A Phylogenomic Profile Of Hemerythrins, The Nonheme Diiron Binding Respiratory Proteins, Xavier Bailly, Stefano Vanin, Christine Chabasse, Kenji Mizuguchi, Serge N. Vinogradov

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Hemerythrins, are the non-heme, diiron binding respiratory proteins of brachiopods, priapulids and sipunculans; they are also found in annelids and bacteria, where their functions have not been fully elucidated.

Results

A search for putative Hrs in the genomes of 43 archaea, 444 bacteria and 135 eukaryotes, revealed their presence in 3 archaea, 118 bacteria, several fungi, one apicomplexan, a heterolobosan, a cnidarian and several annelids. About a fourth of the Hr sequences were identified as N- or C-terminal domains of chimeric, chemotactic gene regulators. The function of the remaining single domain bacterial Hrs remains to be determined. In …

Tissue Engineering The Motoneuron To Muscle Segment Of The Stretch Reflex Arc Circuit Utilizing Micro-Fabrication, Interface Design And Defined Medium Formulation, Mainak Das

Electronic Theses and Dissertations

The stretch reflex circuit is one of the most primitive circuits of mammalian system and serves mainly to control the length of the muscle. It consists of four elements: the stretch sensor (muscle spindle/ intrafusal fiber lie parallel between extrafusal, contractile musculature), extrafusal muscle fiber, sensory neuron and motoneuron. The basic principle of the stretch reflex arc circuit is as follows: whenever there is a sudden stretch in a muscle, it needs to compensate back to its original length so as to prevent any kind of injury. It performs this compensation process using a simple negative feed back circuit called …

The Effect Of Pparγ Activation By Pioglitazone On The Lipopolysaccharide-Induced Pge2 And No Production: Potentialunderlying Alteration Of Signaling Transduction, Bin Xing

University of Kentucky Doctoral Dissertations

Microglia-mediated neuroinflammation plays an important role in the pathogenesis of Parkinson's disease (PD). Uncontrolled microglia activation produces major proinflammatory factors including cyclooxygenase 2 (COX-2) and inducible nitric oxide synthase (iNOS) that may cause dopaminergic neurodegeneration. Peroxisome proliferator-activated receptor γ (PPARγ) agonist pioglitazone has potent antiinflammatory property. We hypothesize pioglitazone protects dopaminergic neuron from lipopolysaccharide (LPS)-induced neurotoxicity by interacting with relevant signal pathways, inhibiting microglial activation and decreasing inflammatory mediators.

First, the neuroprotection of pioglitazone was explored. Second, the signaling transductions such as jun N-terminal kinase (JNK) and the interference with these pathways by pioglitazone were investigated. Third, the effect of …

A Novel And Generalizable Organotypic Slice Platform To Evaluate Stem Cell Potential For Targeting Pediatric Brain Tumors., Shengwen Calvin Li, William Gunter Loudon

Department of Cancer Biology Faculty Papers

Brain tumors are now the leading cause of cancer-related deaths in children under age 15. Malignant gliomas are, for all practical purposes, incurable and new therapeutic approaches are desperately needed. One emerging strategy is to use the tumor tracking capacity inherent in many stem cell populations to deliver therapeutic agents to the brain cancer cells. Current limitations of the stem cell therapy strategy include that stem cells are treated as a single entity and lack of uniform technology is adopted for selection of clinically relevant sub-populations of stem cells. Specifically, therapeutic success relies on the selection of a clinically competent …

Pdgf-Driven Proliferation, Migration, And Il8 Chemokine Secretion In Human Corneal Fibroblasts Involve Jak2-Stat3 Signaling Pathway, Neeraj Vij, Ajay Sharma, Mahesh Thakkar, Sunilima Sinha, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

Purpose: Platelet-derived growth factor (PDGF) is associated with corneal fibroblast migration and proliferation and plays an important role in corneal wound healing. However, the intracellular mechanisms of PDGF-mediated functions in corneal fibroblasts are poorly understood. We tested the hypothesis that PDGF functional activities in the cornea involve the Janus kinase-2/signal transducers and activators of transcription-3 (JAK2-STAT3) signaling pathway and whether PDGF induces the expression of suppressors of cytokine signaling 3 (SOCS3), belonging to the novel family of feedback regulators of cytokine and growth factor activities.

Methods: Human corneal fibroblast (HSF) cultures were used as an in vitro model for functional …