Digital Commons Network^™

Altered Leptin Signaling On Dendritic Cells As A Potential Mechanism For Cancer Immunotherapy, Lorena Y. De Los Santos

Open Access Theses & Dissertations

Leptin is a pleiotropic hormone synthesized primarily by white adipocytes and its receptors are expressed in a variety of tissues and cells such as in the hypothalamus and cells of the immune system. Multiple cell types can produce a considerable amount of leptin such as skeletal muscle, placenta, and osteoblasts to name a few and its synthesis has been shown to be regulated by sex hormones and a broad range of inflammatory mediators. Although leptin has been shown to directly affect immune response, we are interested in how leptin affects dendritic cell function and their ability to induce a proper …

Development Of A Novel Metallo-Lipid Microparticle Delivery System For A Leishmania Mexicana Dna Vaccine Candidate, Joanna B. Valencia

Open Access Theses & Dissertations

ABSTRACT

Background and Significance.

The leishmaniases are an important group of neglected tropical parasitic diseases caused by parasitic protozoa of the genus Leishmania. International health authorities estimate that 350 million people around the world are at risk for contracting leishmaniasis. Two million new cases occur each year and 12 million people are presently infected worldwide. Leishmaniasis is endemic throughout the Americas region including all of Central America, most of South America, Mexico and southern Texas. Leishmania is also considered a threat to the military readiness of U.S. troops deployed to the Middle East or Latin America.

First- and second-line treatments …

Effectiveness Of Artemether-Lumefantrine Provided By Community Health Workers In Under-Five Children With Uncomplicated Malaria In Rural Tanzania: An Open Label Prospective Study, B.E. Ngasala, M. Malmberg, A.M. Carlsson, P.E. Ferreira, M.G. Petzold, D. Blessborn, Y. Bergqvist, J.P. Gil, Zul Premji, A. Martensson

Pathology, East Africa

Background: Home-management of malaria (HMM) strategy improves early access of anti-malarial medicines to high-risk groups in remote areas of sub-Saharan Africa. However, limited data are available on the effectiveness of using artemisinin-based combination therapy (ACT) within the HMM strategy. The aim of this study was to assess the effectiveness of artemether-lumefantrine (AL), presently the most favoured ACT in Africa, in under-five children with uncomplicated Plasmodium falciparum malaria in Tanzania, when provided by community health workers (CHWs) and administered unsupervised by parents or guardians at home.

Methods: An open label, single arm prospective study was conducted in two rural villages …

Addressing The Fertility Needs Of Hiv-Seropositive Males, Brian A. Levine, Sahadat K. Nurudeen, Jennifer T. Gosselin, Mark V. Sauer

Psychology Faculty Publications

An increasing number of serodiscordant couples are utilizing advanced reproductive technologies to address their reproductive needs. Recent literature has demonstrated that it is not only technically possible but also safe to utilize sperm-washing techniques to allow for the creation of embryos, thereby preventing both horizontal and vertical transmission of HIV. This article addresses the strengths and weakness of various reproductive techniques and discusses our experience at Columbia University (NY, USA), the location of the largest HIV-focused fertility program in the USA.

Perception And Practices Of Breastfeeding Of Infants 0-6 Months In An Urban And A Semi-Urban Community In Pakistan: A Cross-Sectional Study, Sumera Ali, Syed Faizan Ali, Ayesha Mallick Imam, Samia Ayub, Abdul Gaffar Billoo

Department of Paediatrics and Child Health

OBJECTIVE: To investigate mother's perception and practices about breastfeeding and their socio-demographic correlate in infants equal to or less than 6 months.

METHODS: A cross-sectional study was carried out on 200 mother-infant pairs who visited the health care centers, Bilal Colony (semi-urban) and the Aga Khan University (urban), for their well baby follow-ups and vaccination using convenient sampling. Frequencies and percentages were computed and Chi-square was used to find associations between socio-demographics of mothers and their perception and practices about breastfeeding.

RESULTS: Exclusive breastfeeding was reported by about 54% of the mothers. Thirty-five percent of the mothers gave prelacteal feed, …

Pseudo-Cushing’S Syndrome In A Hiv Patient With Complete Resolution Following Discontinuation Of Darunavir/Ritonavir, Rashmi Sharma Md, Margaret Hoffman-Terry Md, Facp

Department of Medicine

No abstract provided.

Immunopathology Of Postprimary Tuberculosis: Increased T-Regulatory Cells And Dec-205-Positive Foamy Macrophages In Cavitary Lesions, Kerry J Welsh, Semyon A Risin, Jeffrey K Actor, Robert L Hunter

Faculty, Staff and Student Publications

Postprimary tuberculosis occurs in immunocompetent people infected with Mycobacterium tuberculosis. It is restricted to the lung and accounts for 80% of cases and nearly 100% of transmission. Little is known about the immunopathology of postprimary tuberculosis due to limited availability of specimens. Tissues from 30 autopsy cases of pulmonary tuberculosis were located. Sections of characteristic lesions of caseating granulomas, lipid pneumonia, and cavitary stages of postprimary disease were selected for immunohistochemical studies of macrophages, lymphocytes, endothelial cells, and mycobacterial antigens. A higher percentage of cells in lipid pneumonia (36.1%) and cavitary lesions (27.8%) were positive for the dendritic cell marker …

Alterations In Content And Localization Of Defensins In Rat Ileum And Jejunum Following Ischemia-Reperfusion Specific Peptides, In Specific Places, For Specific Jobs?, Rosemary A Kozar, Rachel J Santora, Brian J Poindexter, Stephen M Milner, Roger J Bick

Faculty, Staff and Student Publications

Objective: To determine alterations in quantities and distributions of natural antimicrobials following ischemia-reperfusion injury. We hypothesized that these compounds would be upregulated in areas of small intestine where changes in permeability and cellular disruption were likely and where protective mechanisms would be initiated. Methods: Rats with ischemia-reperfusion underwent superior mesenteric artery clamping and reperfusion. Shams were subjected to laparotomy but no clamping. Ileum and jejunum were harvested and sectioned, and subjected to fluorescence deconvolution microscopy for determinations of content and localization of rat beta defensins, 1, 2, 3; rat neutrophil protein-1; and cathelicidin LL-37. Modeling was performed to determine cellular …

Complete Genome Sequence Of Treponema Paraluiscuniculi, Strain Cuniculi A: The Loss Of Infectivity To Humans Is Associated With Genome Decay, David Smajs, Marie Zobaníková, Michal Strouhal, Darina Cejková, Shannon Dugan-Rocha, Petra Pospíšilová, Steven J Norris, Tom Albert, Xiang Qin, Kym Hallsworth-Pepin, Christian Buhay, Donna M Muzny, Lei Chen, Richard A Gibbs, George M Weinstock

Faculty, Staff and Student Publications

Treponema paraluiscuniculi is the causative agent of rabbit venereal spirochetosis. It is not infectious to humans, although its genome structure is very closely related to other pathogenic Treponema species including Treponema pallidum subspecies pallidum, the etiological agent of syphilis. In this study, the genome sequence of Treponema paraluiscuniculi, strain Cuniculi A, was determined by a combination of several high-throughput sequencing strategies. Whereas the overall size (1,133,390 bp), arrangement, and gene content of the Cuniculi A genome closely resembled those of the T. pallidum genome, the T. paraluiscuniculi genome contained a markedly higher number of pseudogenes and gene fragments (51). In …

Post-Dural Puncture Posterior Reversible Encephalopathy Syndrome, Fauzia N. Minai, Syeda Fauzia Hasan, Mughis Sheerani

Department of Anaesthesia

We report the case of a young patient with 36 weeks pregnancy, and an acute respiratory infection with severe bronchospasm, who developed an occipital headache and neck pain on the third day of inadvertent dural puncture during placement of combined epidural spinal anaesthesia for caesarian section. It was diagnosed as post-dural puncture headache until generalised tonic clonic siezures occurred the next day raising the suspicion of postpartum eclampsia or meningitis. Posterior reversible encephalopathy syndrome was diagnosed on MRI of the brain which showed features of reversible ischemia in the posterior region of the brain. With anticonvulsant therapy and antibiotics there …

Surgical Site Infections In Gynecologic Oncology Patients: A Retrospective Study Of Patient Characteristics And Intraoperative Parameters, Christine C. Chen Md, Joanne N. Quiñones Md, Msce, Richard Boulay Md, M Bijoy Thomas Md, Martin Martino Md

Department of Obstetrics & Gynecology

No abstract provided.

Β-Lactams Interfering With Pbp1 Induce Panton-Valentine Leukocidin Expression By Triggering Sara And Rot Global Regulators Of Staphylococcus Aureus, Oana Dumitrescu, Priya Choudhury, Sandrine Boisset, Cedric Badiou, Michele Bes, Yvonne Benito, Christiane Wolz, Francois Vandenesch, Jerome Etienne, Ambrose L. Cheung

Dartmouth Scholarship

Previous articles reported that beta-lactam antibiotics increase the expression of Staphylococcus aureus Panton-Valentine leukocidin (PVL) by activating its transcription. We investigated the mechanisms underlying the inductor effect of beta-lactams on PVL expression by determining targets and regulatory pathways possibly implicated in this process. We measured PVL production in the presence of oxacillin (nonselective), imipenem (penicillin-binding protein 1 [PBP1] selective), cefotaxime (PBP2 s

The Pseudomonas Aeruginosa Magnesium Transporter Mgte Inhibits Transcription Of The Type Iii Secretion System, Gregory G. Anderson, Timothy L. Yahr, Rustin R. Lovewell, George A. O'Toole

Dartmouth Scholarship

Pseudomonas aeruginosa is an opportunistic pathogen that causes life-long pneumonia in individuals with cystic fibrosis (CF). These long-term infections are maintained by bacterial biofilm formation in the CF lung. We have recently developed a model of P. aeruginosa biofilm formation on cultured CF airway epithelial cells. Using this model, we discovered that mutation of a putative magnesium transporter gene, called mgtE, led to increased cytotoxicity of P. aeruginosa toward epithelial cells. This altered toxicity appeared to be dependent upon expression of the type III secretion system (T3SS). In this study, we found that mutation of mgtE results in increased T3SS …

Zinc Supplementation For The Prevention Of Pneumonia In Children Aged 2 Months To 59 Months, Zohra S. Lassi, Batool A. Haider, Zulfiqar Ahmed Bhutta

Woman and Child Health

Background:Pneumonia is a leading cause of morbidity and mortality in children younger than five years of age. Most deaths occur during infancy and in low-income countries. Daily regimens of zinc have been reported to prevent acute lower respiratory tract infection and reduce child mortality.
Objectives: To evaluate the effectiveness of zinc supplementation in the prevention of pneumonia in children aged two to 59 months.
Search Methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010, Issue 2), which contains the Acute Respiratory Infections Group's Specialised Register, MEDLINE (1966 to January Week 2, 2010), EMBASE …

The Epidemiology Of Bacterial Vaginosis In Relation To Sexual Behaviour, Hans Verstraelen, Rita Verhelst, Mario Vaneechoutte, Marleen Temmerman

Obstetrics and Gynaecology, East Africa

Background: Bacterial vaginosis (BV) has been most consistently linked to sexual behaviour, and the epidemiological profile of BV mirrors that of established sexually transmitted infections (STIs). It remains a matter of debate however whether BV pathogenesis does actually involve sexual transmission of pathogenic microorganisms from men to women. We therefore made a critical appraisal of the literature on BV in relation to sexual behaviour.

Discussion: G. vaginalis carriage and BV occurs rarely with children, but has been observed among adolescent, even sexually non-experienced girls, contradicting that sexual transmission is a necessary prerequisite to disease acquisition. G. vaginalis carriage is enhanced …

Controversies Of Treatment Modalities For Cerebral Venous Thrombosis, Maria Khan, Ayeesha Kamran Kamal, Mohammad Wasay

Department of Medicine

Cerebral vein thrombosis has been well recognized for nearly two centuries. However, therapeutic options for the condition are limited due to lack of large randomized trials. The various modalities reportedly used include antiplatelets, anticoagulation, fibrinolysis, and mechanical thrombectomy. Of these, antiplatelets are the least studied, and there are only anecdotal reports of aspirin use. Anticoagulation is the most widely used and accepted modality with favorable outcomes documented in two randomized controlled trials. Various fibrinolytic agents have also been tried. Local infusions have shown more promise compared to systemic agents. Similarly, mechanical thrombectomy has been used to augment the effects of …

The Face Of Felt Stigma: Experiences Of Puerto Ricans Living With Hiv In Allentown, Pa, M Reyes Ba, Julio Jiménez Md, Joseph L. Yozviak Do, Facp, Timothy J. Friel Md, D Adams Psyd, Cynthia Beitler, Eric J. Gertner Md, Mph, E Rivera Ba, L Santiago Phd

Department of Medicine

No abstract provided.

A Severe Case Of Necrotizing Fasciitis Of The Abdomen: A Survivor Story, Karin Mcconville Md, Dale A. Dangleben Md, Rovinder S. Sandhu Md

Department of Surgery

No abstract provided.

Successful Management Of Invasive Aspergillosis With Voriconazole And Amphoteracin B Therapy In A Patient With Acute Mycloid Leukemia (Aml-M2), Nauman Fazal Manzoor, Sidra Azim, Zehra Fadoo

Department of Paediatrics and Child Health

An eleven-year-old boy presented with one month's history of fever and weight loss. He was diagnosed with Acute Mycloid Leukemia (AML-M2). During treatment he developed recurrent infections with neutropenia requiring prolonged antibiotics and subsequently developed invasive aspergillosis. He was treated with amphotericin B and Voriconazole. This case shows the efficacy and safety of combined antifungal therapy, including voriconazole, for invasive aspergillosis complicating AML.

Compositions And Methods For Inhibiting Drusen Complement Components C3a And C5a For The Treatment Of Age-Related Macular Degeneration, Jayakrishna Ambati

Ophthalmology and Visual Science Faculty Patents

Activated C3 (C3a) and its receptor (C3aR) and activated C5 (C5a) and its receptor (C5aR) have been shown to induce vascular endothelial growth factor (VEGF) expression in vitro and in vivo. Compositions and methods for inhibiting C3a, C3aR, C5a and C5aR for the treatment and/or prevention of neovascular disease are provided. Also provided are Novel therapeutic targets and diagnostic markers for choroidal neovascularization.

Molecular Mechanism Of Agc Kinases In Human Malignant, Shaokun Shu

USF Tampa Graduate Theses and Dissertations

The maintenance of normal cell function and tissue homeostasis is dependent on the precise regulation of multiple signaling pathways that control cellular decisions to either proliferate, differentiate, arrest cell growth, or initiate programmed cell death (apoptosis). Cancer arises when clones of mutated cells escape this balance and proliferate inappropriately without compensatory apoptosis. Deregulated cell growth occurs as a result of perturbed signal transduction that modulates or alters cellular behavior or function to keep the critical balance between the rate of cell-cycle progression (cell division) and cell growth (cell mass) on one hand, and programmed cell death (apoptosis, autophagy) on the …

Interferon Regulatory Factor 3-Dependent Pathways Are Critical For Control Of Herpes Simplex Virus Type 1 Central Nervous System Infection, Vineet D. Menachery, Tracy J. Pasieka, David A. Leib

Dartmouth Scholarship

The initiation of the immune response at the cellular level relies on specific recognition molecules to rapidly signal viral infection via interferon (IFN) regulatory factor 3 (IRF-3)-dependent pathways. The absence of IRF-3 would be expected to render such pathways inoperative and thereby significantly affect viral infection. Unexpectedly, a previous study found no significant change in herpes simplex virus (HSV) pathogenesis in IRF-3^−/− mice following intravenous HSV type 1 (HSV-1) challenge (K. Honda, H. Yanai, H. Negishi, M. Asagiri, M. Sato, T. Mizutani, N. Shimada, Y. Ohba, A. Takaoka, N. Yoshida, and T. Taniguchi, Nature 434:772-777, 2005). In contrast, the …

Enterococcus Faecalis Rnjb Is Required For Pilin Gene Expression And Biofilm Formation, Peng Gao, Kenneth L Pinkston, Sreedhar R Nallapareddy, Ambro Van Hoof, Barbara E Murray, Barrett R Harvey

Faculty, Staff and Student Publications

Pili in Gram-positive bacteria play a major role in the colonization of host tissue and in the development of biofilms. They are promising candidates for vaccines or drug targets since they are highly immunogenic and share common structural and functional features among various Gram-positive pathogens. Numerous publications have helped build a detailed understanding of pilus surface assembly, yet regulation of pilin gene expression has not been well defined. Utilizing a monoclonal antibody developed against the Enterococcus faecalis major pilus protein EbpC, we identified mutants from a transposon (Tn) insertion library which lack surface-exposed Ebp pili. In addition to insertions in …

Concurrent Sexual Partnerships Do Not Explain The Hiv Epidemics In Africa: A Systematic Review Of The Evidence, Larry Sawers, Eileen Stillwaggon

Economics Faculty Publications

The notion that concurrent sexual partnerships are especially common in sub-Saharan Africa and explain the region’s high HIV prevalence is accepted by many as conventional wisdom. In this paper, we evaluate the quantitative and qualitative evidence offered by the principal proponents of the concurrency hypothesis and analyze the mathematical model they use to establish the plausibility of the hypothesis.

We find that research seeking to establish a statistical correlation between concurrency and HIV prevalence either finds no correlation or has important limitations. Furthermore, in order to simulate rapid spread of HIV, mathematical models require unrealistic assumptions about frequency of sexual …

Relationship Between Maternal Methadone Dose At Delivery And Neonatal Abstinence Syndrome., Neil S., Seligman, Christopher V. Almario, Edward J. Hayes, Kevin C. Dysart, Vincenzo Berghella, Jason K. Baxter

Department of Obstetrics and Gynecology Faculty Papers

OBJECTIVE: To estimate the relationship between maternal methadone dose and the incidence of neonatal abstinence syndrome (NAS).

STUDY DESIGN: We performed a retrospective cohort study of pregnant women treated with methadone for opiate addiction who delivered live-born neonates between 1996 and 2006. Four dose groups, on the basis of total daily methadone dose, were compared (160 mg/d). The primary outcome was treatment for NAS. Symptoms of NAS were objectively measured with the Finnegan scoring system, and treatment was initiated for a score>24 during the prior 24 hours.

RESULTS: A total of 330 women treated with methadone and their 388 …

Klebsiella Osteomyelitis Of The Right Humerus Involving The Right Shoulder Joint In An Infant, Maqbool Qadir, Syed Rehan Ali, Mumtaz Lakhani, Pervaiz Hashmi, Ahsen Amirali

Department of Paediatrics and Child Health

Osteomyelitis in newborn infants is a rare infection. Lower extremity joints are commonly affected. Most of the cases have a haematogenous spread. Aerobes are the common group of organism involved, of which Staphylococcus aureus is the commonest. Klebsiella osteomyelitis has been reported as a cause of Osteomyelitis. However, to the best of our knowledge, this is the first case report of Klebsiella pneumoniae associated osteomyelitis in an infant from Pakistan.

Prevalences Of Giardia Lamblia And Cryptosporidium Parvum Infection In Adults Presenting With Chronic Diarrhoea, Javed Yakoob, Zaigham Abbas, M. Asim Beg, Shagufta Naz, Rustam Khan, Muhammad Islam, Wasim Jafri

Section of Gastroenterology

iardia lamblia and Cryptosporidium parvum are both waterborne pathogens associated with diarrhoea in developing countries. In a recent study based at the Aga Khan University in Karachi, 334 adults aged 16–83 years (178 patients with chronic diarrhoea and 156 diarrhoea-free volunteers who acted as controls) were checked for infection with these parasites, using stool microscopy and/or PCR. Overall, 21 (6.3%) and 29 (8.7%) of the subjects were found positive for G. lamblia by microscopy and PCR, respectively, while the corresponding values for C. parvum were 13 (3.9%) and 14 (4.2%). Although, compared with the diarrhoea-free controls, the patients with diarrhoea …

Primary Human Mammary Epithelial Cells Endocytose Hiv-1 And Facilitate Viral Infection Of Cd4+ T Lymphocytes, Stephanie M. Dorosko, Ruth I. Connor

Dartmouth Scholarship

The contribution of mammary epithelial cells (MEC) to human immunodeficiency virus type 1 (HIV-1) in breast milk remains largely unknown. While breast milk contains CD4(+) cells throughout the breast-feeding period, it is not known whether MEC directly support HIV-1 infection or facilitate infection of CD4(+) cells in the breast compartment. This study evaluated primary human MEC for direct infection with HIV-1 and for indirect transfer of infection to CD4(+) target cells. Primary human MEC were isolated and assessed for expression of HIV-1 receptors. MEC were exposed to CCR5-, CXCR4- and dual-tropic strains of HIV-1 and evaluated for viral reverse transcription …

The Staphylococcus-Specific Gene Rsr Represses Agr And Virulence In Staphylococcus Aureus, Sandeep Tamber, Dindo Reyes, Niles P. Donegan, Joseph D. Schwartzman, Ambrose L. Cheung, Guido Memmi

Dartmouth Scholarship

The expression of virulence factors in Staphylococcus aureus is tightly coordinated by a vast network of regulatory molecules. In this report, we characterize a genetic locus unique to staphylococci called rsr that has a role in repressing two key virulence regulators, sarR and agr. Using strain SH1000, we showed that the transcription of virulence effectors, such as hla, sspA, and spa, is altered in an rsr mutant in a way consistent with agr upregulation. Analysis of RNAIII expression of the agr locus in rsr and rsr-sarR mutants indicated that rsr likely contributes to agr expression independently …

Mononucleosis And Antigen-Driven T Cell Responses Have Different Requirements For Interleukin-2 Signaling In Murine Gammaherpesvirus Infection, Michael Molloy, Weijun Zhang, Edward Usherwood

Dartmouth Scholarship

Interleukin-2 (IL-2) has been implicated as being necessary for the optimal formation of primary CD8⁺ T cell responses against various pathogens. Here we have examined the role that IL-2 signaling plays in several aspects of a CD8⁺ T cell response against murine gammaherpesvirus 68 (MHV-68). Exposure to MHV-68 causes a persistent infection, along with infectious mononucleosis, providing a model for studying these processes in mice. Our study indicates that CD25 is necessary for optimal expansion of the antigen-specific CD8⁺ T cell response but not for the long-term memory response. Contrastingly, IL-2 signaling through CD25 is absolutely required …