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Epignetics And Allergic Disease, Jacob Sweeney '11

Honor Scholar Theses

In this thesis I will propose a novel framework for understanding allergy. I will argue that exposure to certain early-life environments lead to life-long allergic disease through epigenetic mechanisms. Although my argument currently exists as an unsubstantiated hypothesis, I will review indirect evidence that I have gathered throughout the immunologic and epigenetic literature to support my claim. | will then propose a set of experiments which will test my hypothesis. This thesis will address current scientific “hot topics” and their implications will challenge fundamental tenants of biology. Rather than jumping straight into the argument I will begin with some background …

A Novel Approach For A New Era: Successful Integration Of Multidisciplinary, Hepatitis C Care Within An Established Hiv Primary Care Practice, Joseph L. Yozviak Do, Facp, Orlando J. Penaloza Md, Facp, Timothy J. Friel Md

Department of Medicine

No abstract provided.

Effect Of Animal Facility Construction On Basal Hypothalamic-Pituitary-Adrenal And Renin-Aldosterone Activity In The Rat, Hershel Raff, Eric D. Bruder, William E. Cullinan, Dana R. Ziegler, Eric P. Cohen

Biomedical Sciences Faculty Research and Publications

Nearby construction can cause subtle, but important activation of the hypothalamic-pituitary-adrenal axis in laboratory rats.

Although loud noise and intense vibration are known to alter the behavior and phenotype of laboratory animals, little is known about the effects of nearby construction. We studied the effect of a nearby construction project on the classic stress hormones ACTH, corticosterone, renin, and aldosterone in rats residing in a barrier animal facility before, for the first 3 months of a construction project, and at 1 month after all construction was completed. During some of the construction, noise and vibrations were not obvious to investigators …

Human Papillomavirus Genotype Concordance Within Zambian Couples, Kgomotso Makhaola

School of Biological Sciences: Dissertations, Theses, and Student Research

Human Papillomavirus (HPV) is strongly associated with the development of cervical cancer, and has also been identified in other anogenital cancers such as penile, oral, and anal cancers. In regions like Sub Saharan Africa where the prevalence of HIV/AIDS is high,   increased rates of HPV infections have also been observed, however the effect of HIV/AIDS on the transmission of HPV is not yet well understood.  In this study specimens for HIV, HPV testing and pathology were collected from male participants and their female partners at a Urology department in Lusaka University Teaching Hospital, Zambia. Seventy four samples were collected but …

Advances And Future Challenges In Adenoviral Vector Pharmacology And Targeting, Reeti Khare, Christopher Y. Chen, Eric A. Weaver, Michael A. Barry

Nebraska Center for Virology: Faculty Publications

Adenovirus is a robust vector for therapeutic applications, but its use is limited by our understanding of its complex in vivo pharmacology. In this review we describe the necessity of identifying its natural, widespread, and multifaceted interactions with the host since this information will be crucial for efficiently redirecting virus into target cells. In the rational design of vectors, the notion of overcoming a sequence of viral “sinks” must be combined with re-targeting to target populations with capsid as well as shielding the vectors from pre-existing or toxic immune responses. It must also be noted that most known adenoviral pharmacology …

Whole-Genome Sequencing Of Staphylococcus Aureus Strain Rn4220, A Key Laboratory Strain Used In Virulence Research, Identifies Mutations That Affect Not Only Virulence Factors But Also The Fitness Of The Strain, Dhanalakshmi Nair, Guido Memmi, David Hernandez, Jonathan Bard, Marie Beaume, Steven Gill, Patrice Francois, Ambrose L. Cheung

Dartmouth Scholarship

Staphylococcus aureus RN4220, a cloning intermediate, is sometimes used in virulence, resistance, and metabolic studies. Using whole-genome sequencing, we showed that RN4220 differs from NCTC8325 and contains a number of genetic polymorphisms that affect both virulence and general fitness, implying a need for caution in using this strain for such studies.

Low Levels Of Hydrogen Peroxide Stimulate Corneal Epithelial Cell Adhesion, Migration, And Wound Healing, Qing Pan, Wen-Ya Qiu, Ya-Nan Huo, Yu-Feng Yao, Marjorie F. Lou

School of Veterinary and Biomedical Sciences: Faculty Publications

PURPOSE. Intracellular reactive oxygen species have been reported to associate with growth factor and integrin signalings in promoting cell adhesion in many cell types. This study is to explore if exogenous H2O2 at low levels can be beneficial to cell adhesion, migration, and wound healing.

METHODS. Primary rabbit corneal epithelial cells treated with 0–70 M H2O2 were tested for viability by MTT assay, adhesion by centrifugation assay, focal contacts of vinculin and F-actin by immunofluorescence, activated Src(pY416), EGF receptor (pY845), vinculin(pY1065), FAK(pY397), and FAK(pY576) by immunoblotting. Cell migration was examined with 0–50 M H2O2 using the scratch wound technique. Corneal …

Improving Outcomes For Hispanic Patients Undergoing Peginterferon/Ribavirin Therapy For Chronic Hepatitis C In An Internist-Led, Multidisciplinary, Multi-Cultural Practice: A Unique Application Of The Medical, Joseph L. Yozviak Do, Facp, Orlando J. Penaloza Md, Facp, Judith A. Knoop

Department of Medicine

No abstract provided.

Impaired Memory Cd8 T-Cell Responses Against An Immunodominant Retroviral Cryptic Epitope, Melanie R. Rutkowski, Cynthia A. Stevens, William R. Green

Dartmouth Scholarship

The immunodominant cryptic epitope SYNTGRFPPL, encoded within open reading frame 2 of the LP-BM5 retroviral gag gene, is critical for protection against retroviral-induced pathogenesis. The goal of this study was to dissect the memory response against this unique immunodominant cryptic epitope. Unlike the protective acute effector population of SYNTGRFPPL-specific CD8 T cells, long-lived SYNTGRFPPL-specific CD8 T cells lacked the ability to protect susceptible mice infected with LP-BM5 retrovirus. Compared to memory CD8 T cells against a conventional epitope with similar MHC-I specificity, primed and restimulated using similar conditions, long-lived SYNTGRFPPL-specific CD8 T cells were impaired in their ability to recall …

Comparative Gender Analysis Of The Efficacy And Safety Of Atazanavir/Ritonavir And Lopinavir/Ritonavir At 96 Weeks In The Castle Study., Kathleen E Squires, Margaret Johnson, Rong Yang, Jonathan Uy, Louise Sheppard, Judith Absalon, Donnie Mcgrath

Department of Medicine Faculty Papers

OBJECTIVES: To examine whether the overall results of the CASTLE study pertain to both genders, we analysed the efficacy and safety of atazanavir/ritonavir and lopinavir/ritonavir in 277 female and 606 male patients in the open-label, multinational trial over 96 weeks. The trial is registered with ClinicalTrials.gov, number NCT00272779.

METHODS: Treatment-naive patients aged ≥ 18 years with HIV-1 RNA ≥ 5000 copies/mL were randomized to receive either atazanavir/ritonavir 300/100 mg once daily or lopinavir/ritonavir 400/100 mg twice daily, with fixed-dose tenofovir/emtricitabine 300/200 mg once daily.

RESULTS: At week 96, confirmed virological response rates (HIV RNA <50 copies>/mL; intent-to-treat analysis) were higher in …

The Role Of The Pediatrican In The Effort To Prevent Congenital Malformations, Robert L. Brent Dr.

The Selected Works of Robert Brent

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Critical Role Of Leucine-Valine Change In Distinct Low Ph Requirements For Membrane Fusion Between Two Related Retrovirus Envelopes, Marceline Côté, Yi-Min Zheng, Kun Li, Shi-Hua Xiang, Lorraine M. Albritton, Shan-Lu Liu

Nebraska Center for Virology: Faculty Publications

Many viruses use a pH-dependent pathway for fusion with host cell membrane, the mechanism of which is still poorly understood. Here we report that a subtle leucine (Leu)-valine (Val) change at position 501 in the envelope glycoproteins (Envs) of two related retroviruses, jaagsiekte sheep retro-virus (JSRV) and enzootic nasal tumor virus (ENTV), is responsible for their distinct low pH requirements for membrane fusion and infection. The Leu and Val residues are predicted to reside within the C-terminal heptad repeat (HR2) region of JSRV and ENTV Envs, particularly proximal to the hairpin turn of the putative six-helix bundle (6HB). Substitution of …

Hiv-1 Effects On Neuropsychological Performance In A Resource-Limited Country, Zambia, Gabriel Holguin, Mwanza Banda, Elizabeth J. Willen, Costantine Malama, Kaseya O. Chiyenu, Victor C. Mudenda, Charles Wood

Nebraska Center for Virology: Faculty Publications

Zambia has substantially been affected by the HIV/AIDS epidemic with prevalence rates at 14% in a population estimated at 12 million. Yet, the extent of HIV-associated neurocognitive disorders (HAND) in this population remains to be clearly understood. A series of culturally appropriate neuropsychological (NP) assessments [International HIV Dementia Scale (IHDS), Color Trails Test 1 and 2, Grooved pegboard Test, and Time Gait Test] were used to test the effects of HIV on NP performance of HIV seropositive and seronegative individuals. Twenty-two percent HIV positive individuals ARV naïve met the criteria for IHDS-defined NP impairment. Gender significantly influenced the performance on …

Characterization Of Species C Human Adenovirus Serotype 6 (Ad6), Eric A. Weaver, Reeti Khare, Mathew L. Hillestad, Donna Palmer, Philip Ng, Michael A. Barry

Nebraska Center for Virology: Faculty Publications

Adenovirus serotype (Ad5) is the most studied Ad. Ad1, 2, and 6 are also members of species C Ad and are presumed to have biologies similar to Ad5. In this work, we have compared the ability of Ad1, 2, 5, and 6 to infect liver and muscle after intravenous and intramuscular injection. We found that Ad6 was surprisingly the most potent at liver gene delivery and that Ad1 and Ad2 were markedly weaker than Ad5 and 6. To understand these differences, we sequenced the Ad6 genome. This revealed that the Ad6 fiber protein is surprisingly three shaft repeats shorter than …

Generation Of A Kupffer Cell-Evading Adenovirus For Systemic And Liver-Directed Gene Transfer, Reeti Khare, Shannon M. May, Francesco Vetrini, Eric A. Weaver, Donna Palmer, Amanda Rosewell, Nathan Grove, Philip Ng, Michael A. Barry

Nebraska Center for Virology: Faculty Publications

As much as 90% of an intravenously (i.v.) injected dose of adenovirus serotype 5 (Ad5) is absorbed and destroyed by liver Kupffer cells. Viruses that escape these cells can then transduce hepatocytes after binding factor X (FX). Given that interactions with FX and Kupffer cells are thought to occur on the Ad5 hexon protein, we replaced its exposed hypervariable regions (HVR) with those from Ad6. When tested in vivo in BALB/c mice and in hamsters, the Ad5/6 chimera mediated >10 times higher transduction in the liver. This effect was not due to changes in FX binding. Rather, Ad5/6 appeared to …

Roles Of The 15-Kda Selenoprotein (Sep15) In Redox Homeostasis And Cataract Development Revealed By The Analysis Of Sep 15 Knockout Mice, Marina V. Kasaikina, Dmitri E. Fomenko, Vyacheslav M. Labunskyy, Salil A. Lachke, Wenya Qiu, Juliet A. Moncaster, Jie Zhang, Mark W. Wojnarowicz, Sathish Kumar Natarajan, Mikalai I. Malinouski, Ulrich Schweizer, Petra A. Tsuji, Bradley A. Carlson, Richard L. Maas, Marjorie F. Lou, Lee E. Goldstein, Dolph L. Hatfield, Vadim N. Gladyshev

School of Veterinary and Biomedical Sciences: Faculty Publications

The 15-kDa selenoprotein (Sep15) is a thioredoxin-like, endoplasmic reticulum-resident protein involved in the quality control of glycoprotein folding through its interaction with UDP-glucose:glycoprotein glucosyltransferase. Expression of Sep15 is regulated by dietary selenium and the unfolded protein response, but its specific function is not known. In this study, we developed and characterized Sep15 KO mice by targeted removal of exon 2 of the Sep15 gene coding for the cysteinerich UDP-glucose:glycoprotein glucosyltransferase-binding domain. These KO mice synthesized a mutant mRNA, but the shortened protein product could be detected neither in tissues nor in Sep15 KO embryonic fibroblasts. Sep15 KO mice were viable …

Management Of Community-Acquired Acute Bacterial Cystitis In Turkey, Ömer Coşkun, Hakan Erdem, Ali̇ Avci

Turkish Journal of Medical Sciences

Community acquired acute bacterial cystitis (CA-ABC) is one of the most common infectious presentations in the community. This paper aims to provide a rational approach in the management of CA-ABC based on local Turkish data. Materials and methods: The publications evaluating the microbiological data obtained from CA-ABC cases were searched in both Turkish and international databases. Results: Fosfomycin and nitrofurantain appear to be baseline antibiotics while the empirical use of trimethoprim sulfamethoxazole, amoxicillin clavulanate, and first and second generation cephalosporins seems to be unreliable in Turkey. Moreover, quinolones seem to be at the edge with resistance rates up to 20%. …

Are Gram Negative Bacilli A Threat For Prosthetic Joint Replacements? Experience Of A University Hospital, Emi̇ne Alp Meşe, Mehmet Halici, Emi̇ne Bi̇lge Kiran, Mahmut Argün, Mehmet Doğanay

Turkish Journal of Medical Sciences

No abstract provided.

Evaluation Of Rubella, Toxoplasma Gondii, And Cytomegalovirus Seroprevalences Among Pregnant Women In Denizli Province, Aysun Karabulut, Yusuf Polat, Meral Türk, Yasemi̇n Işik Balci

Turkish Journal of Medical Sciences

There is no national screening program for rubella, Toxoplasma gondii, and cytomegalovirus (CMV) infections for pregnant women in Turkey. The purpose of this study was to determine the prevalence of these infections among pregnant women in Denizli province, and to review seroprevalences reported from different regions of Turkey. Materials and methods: Between April 2008 and April 2009, 1268 women were investigated for rubella, 1102 for toxoplasma, and 1000 women for CMV seroprevalences in the first trimester of pregnancy. Toxoplasma and rubella IgM and IgG antibodies were assayed by the automated Vitros ECiQ system based on an immunometric technique. Cytomegalovirus IgM …

Assessment Of The Findings On The Existence Of Complications In Brucellosis, Cemal Bulut, Meltem Arzu Yetki̇n, Gülruhsar Yilmaz, Fatma Şebnem Erdi̇nç, Çi̇ğdem Ataman Hati̇poğlu, Sami̇ Kinikli, Behi̇ç Oral, Necla Tülek, Ali̇ Pekcan Demi̇röz

Turkish Journal of Medical Sciences

Brucellosis is a prevalent disease in Turkey. The object of this study was to assess the findings in brucellosis cases with and without complications. Materials and methods: A total of 324 patients diagnosed with brucellosis between 1999 and 2005 were reviewed retrospectively. The diagnosis of brucellosis was established serologically and/or by positivite blood culture. Epidemiologic features, clinical symptoms, and laboratory findings of the patients were assessed in both complicated and noncomplicated brucellosis cases by univariate and multivariate analysis. Results: The mean age of patients was 44.0 ± 18.3 years (range 15-83 years). In addition, 56% of the patients were male. …

Two Cases Of H1n1 Influenza Infection As The Initial Presentation Of Acute Leukemia, Leylagül Kaynar, Serdar Şivgin, Osman Başpinar, Fati̇h Kurnaz, Afra Yildirim, Gökhan Metan

Turkish Journal of Medical Sciences

Pandemic 2009 influenza A virus (H1N1) is a new influenza virus causing illness in human populations. Immunocompromised patients are at high risk for the acquisition of influenza and serious influenza-associated complications. However, there are no reports about patients with both newly diagnosed acute leukemia and H1N1 influenza infection. We reported 2 cases of previously healthy patients with H1N1 influenza infection as the initial presentation of acute leukemia.

A Comparison Of Two Different Fluorochrome Stains For The Detection Of Acid-Fast Bacilli In Sputum Specimens*, Vi̇ldan Avkan Oğuz, Nurbanu Sezak, Aygün Öztop, Nur Yapar, Süheyla Sürücüoğlu, Ayşe Yüce

Turkish Journal of Medical Sciences

The early diagnosis of active tuberculosis still depends on the presence of acid-fast bacilli (AFB) in stained sputum smears. In this study, our aim was to investigate the efficiency and cost-effectiveness of two different fluorochrome stains. Materials and methods: A total of 1013 sputum specimens were collected from 642 patients. Three smears and cultures were prepared from each specimen. Double-blind and prospective laboratory procedures were performed. Slides were stained with a commercial auramine/acridine orange kit (Stain 1), an in-house preparation of auramine- rhodamine/KMnO4 (Stain 2) and a Ziehl-Neelsen stain (EZN). Results: Of the 1013 specimens, 101 were culture positive. Among …

A Pooled Analysis Of The Resistance Patterns Of Escherichia Coli Strains Isolated From Urine Cultures In Turkey: A Comparison Of The Periods 1997-2001 And 2002-2007, Meltem Işikgöz Taşbakan, Hüsnü Pullukçu, Oğuz Reşat Si̇pahi̇, Tansu Yamazhan, Bi̇lgi̇n Arda, Sercan Ulusoy

Turkish Journal of Medical Sciences

To compare the resistance patterns of Escherichia coli strains reported to be isolated from urine cultures in published medical literature from Turkey in 1997-2001 and 2002-September 2007. Materials and methods: To find the published series, 3 national databases (Ulakbim Turkish Medical Literature database, http://www.turkishmedline.com, http://medline.pleksus.com.tr), and 2 international databases (Pubmed and Science Citation Index (SCI)) were searched. Results: Data for 25,577 E. coli strains were obtained from 53 articles (28 articles from 1997-2001, 25 from 2002-2007). Of these strains 18,106 were isolated from outpatients, whereas 7471 were from inpatients. When the strains isolated from outpatients were evaluated, there was a …

Human Brucellosis In Turkey: A Review Of The Literature Between 1990 And 2009, Şebnem Çalik, Ayşe Deni̇z Gökengi̇n

Turkish Journal of Medical Sciences

Brucellosis is a systemic infection, which may involve any organ or system of the body. The aim of this study was a review of the literature related to human brucellosis in Turkey. Materials and methods: In order to find the published reports on this subject, 3 national databases (TÜBİTAK-ULAKBİM Turkish Medical Literature database, http://www.turkishmedline.com, http://medline.pleksus.com.tr) and 2 international databases [Index Medicus and Science Citation Index (SCI)-expanded] were searched. In addition to the databases, abstracts of congresses held by the Turkish Clinical Microbiology and Infectious Diseases Association and the Antibiotic and Chemotherapy Association were searched for reports about brucellosis. Results: The …

Retrospective Evaluation Of Laboratory-Confirmed And Recovered Cases Of Influenza A(H1n1)V, Funda Sevencan, Mehmet Meli̇kşah Ertem, Neval Özçullu, Vedat Dorman, Abdulvahi̇t Ormanli, Namik Kemal Kubat, Nurhan Albayrak, Ayşe Başak Altaş

Turkish Journal of Medical Sciences

To retrospectively evaluate patients that were diagnosed with H1N1 and recovered from the disease in the initial period of an influenza A(H1N1)v epidemic in the province of Diyarbakir. It is estimated that 34-67 million individuals around the world have been infected by influenza A(H1N1)v, that 154,000-303,000 individuals have been hospitalized, and that 7000-13,000 individuals have lost their lives. Materials and methods: We were able to include 250 of 362 cases (69.0%) of confirmed influenza A(H1N1)v, from which the patients recovered, from the samples received between 19 October and 3 December 2009 after a pandemic alarm was given in the province …

Surveillance Of Antimicrobial Use In A Turkish University Hospital, Rabi̇n Saba, Di̇lara İnan, Özge Turhan, Ata Nevzat Yalçin, Fi̇li̇z Günseren, Lati̇fe Mamikoğlu

Turkish Journal of Medical Sciences

To determine antimicrobial use in a university hospital in Turkey and compare it with United States antimicrobial use and resistance (US-AUR) and International Nosocomial Infection Control Consortium (INICC) rates. Materials and methods: This was a prospective surveillance study done between January 2007 and December 2007. The data are standardized by use of the defined daily dose (DDD) for each antimicrobial group and by calculating use per 1000 patients (antibiotic use density-AD). Results: Data on 35,936 patients with a total of 215,616 patient-days were analyzed. Ampicillin group (mainly with a beta lactamase inhibitor) has the highest AD in ICU and non-ICU …

The Prevalence Of Tuberculin Skin Test Positivity And The Effect Of Bcg Vaccinations On Tuberculin Induration Size In The Eastern Mediterranean Region Of Turkey, Ferda Kazanci, Ekrem Güler, Canan Eren Dağli, Mesut Gari̇pardiç, Mehmet Davutoğlu, Esen İspi̇roğlu, Hasan Çeti̇n Ekerbi̇çer, Hamza Karabi̇ber

Turkish Journal of Medical Sciences

To evaluate the prevalence of tuberculin skin test (TST) positivity in Kahramanmaraş and interpret the size of purified protein derivative (PPD) induration with respect to the number of Bacillus Calmette-Guerin (BCG) scars and other factors. Materials and methods: A total of 2979 school children between the ages of 7 and 17 years were evaluated. On the basis of socioeconomic levels, 11 schools were selected and categorized into 3 subgroups: schools in the suburbs of the city (Group 1), schools in the city center (Group 2), and private schools (Group 3). Children were injected with 5 TU/0.1 mL of PPD and …

Clinical Significance And Staphylococcal Cassette Chromosome Mec (Sccmec) Characterization Of Coagulase-Negative Staphylococci Isolated From Blood Cultures, Gürkan Mert, Abdullah Kiliç, Orhan Bedi̇r, Ahmet Celal Başustaoğlu

Turkish Journal of Medical Sciences

To describe the true coagulase-negative staphylococci (CoNS) bacteremia rate compared with contaminants, and to determine the SCCmec types in methicillin-resistant staphylococci and evaluate the diversity between methicillin-resistant CoNS (MRCoNS) and methicillin-resistant Staphylococcus aureus (MRSA) isolates during a 10-month study period. Materials and methods: The true CoNS bacteremia or bloodstream infection episode was defined on the basis of previous studies on CoNS bacteremia and the definitions of the Centers for Disease Control and Prevention. SCCmec types were determined by using the real-time PCR method. A total of 357 staphylococci isolates, including 313 CoNS and 44 S. aureus, were obtained from 462 …

Knowledge Discovery For The Treatment Of Bacteria Affecting The Liver, Pinar Yildirim, Kağan Çeken, Osman Saka

Turkish Journal of Medical Sciences

Biomedical information is buried in millions of published articles, and so it is necessary to use text mining techniques to skim published articles for relevant information. In this study, we used biomedical text mining techniques to introduce a liver bacterial infection knowledge-acquisition information system. Materials and methods: Bacteria names were selected from Medline MeSH data and it was searched to identify the most frequent bacteria associated with the liver using a text mining system and time based analyses were used to show the evolution of treatments. Results: Liver infections constitute a major threat to public health, and our study shows …

Banf1 Is Required To Maintain The Self-Renewal Of Both Mouse And Human Embryonic Stem Cells, Jesse L. Cox, Sunil K. Mallanna, Briana D. Ormsbee, Michelle Desler, Matthew S. Wiebe, Angie Rizzino

Nebraska Center for Virology: Faculty Publications

Self-renewal is a complex biological process necessary for maintaining the pluripotency of embryonic stem cells (ESCs). Recent studies have used global proteomic techniques to identify proteins that associate with the master regulators Oct4, Nanog, and Sox2 in ESCs or in ESCs during the early stages of differentiation. Through an unbiased proteomic screen, Banf1 was identified as a Sox2- associated protein. Banf1 has been shown to be essential for worm and fly development but, until now, its role in mammalian development and ESCs has not been explored. In this study, we examined the effect of knocking down Banf1 on ESCs. We …