Medical Sciences Commons^™

Evaluation Of Cholera Vaccines Formulated With Toxin-Coregulated Pilin Peptide Plus Polymer Adjuvant In Mice, Jia-Yan Wu, William F. Wade, Ronald K. Taylor

Dartmouth Scholarship

Cholera is an acute diarrheal disease that is caused by the gram-negative bacterium Vibrio cholerae. The low efficacy of currently available killed-whole-cell vaccines and the reactinogenicity coupled with potential reversion of live vaccines have thus far precluded widespread vaccination for the control of cholera. Recent studies on the molecular nature of the virulence components that contribute to V. cholerae pathogenesis have provided insights into possible approaches for the development of a defined subunit cholera vaccine. Genetic analysis has demonstrated that the toxin-coregulated pilus (TCP) is the major factor that contributes to colonization of the human intestine by V. cholerae. In …

Immune Response Genes Modulate Serologic Responses To Vibrio Cholerae Tcpa Pilin Peptides, Michael D. Meeks, Terri K. Wade, Ronald K. Taylor, William F. Wade

Dartmouth Scholarship

Cholera is an enteric disease caused by Vibrio cholerae. Toxin-coregulated pilus (TCP), a type 4 pilus expressed by V. cholerae, is a cholera virulence factor that is required for host colonization. The TCP polymer is composed of subunits of TcpA pilin. Antibodies directed against TcpA are protective in animal models of cholera. While natural or recombinant forms of TcpA are difficult to purify to homogeneity, it is anticipated that synthesized TcpA peptides might serve as immunogens in a subunit vaccine. We wanted to assess the potential for effects of the immune response (Ir) gene that could complicate a peptide-based …

Anti-Class Ii Monoclonal Antibody-Targeted Vibrio Cholerae Tcpa Pilin: Modulation Of Serologic Response, Epitope Specificity, And Isotype, Jia-Yan Wu, Ronald K. Taylor, William F. Wade

Dartmouth Scholarship

Toxin-coregulated pilus (TCP) is a colonization factor required for cholera infection. It is not a strong immunogen when delivered in the context of whole cells, yet pilus subunits or TcpA derivative synthetic peptides induce protective responses. We examined the efficacy of immunizing mice with TCP conjugated to anti-class II monoclonal antibodies (MAb) with or without the addition of cholera toxin (CT) or anti-CD40 MAb to determine if the serologic response to TcpA could be manipulated. Anti-class II MAb-targeted TCP influenced the anti-TCP peptide serologic response with respect to titer and isotype. Responses to TcpA peptide 4 were induced with class …

Evaluation Of A Tetracycline-Inducible Promoter In Staphylococcus Aureus In Vitro And In Vivo And Its Application In Demonstrating The Role Of Sigb In Microcolony Formation, B. T. Bateman, N. P. Donegan, T. M. Jarry, M. Palma

Dartmouth Scholarship

An inducible promoter system provides a powerful tool for studying the genetic basis for virulence. A variety of inducible systems have been used in other organisms, including pXyl-xylR-inducible promoter, the pSpac-lacI system, and the arabinose-inducible P_BAD promoter, but each of these systems has limitations in its application to Staphylococcus aureus. In this study, we demonstrated the efficacy of a tetracycline-inducible promoter system in inducing gene expression in S. aureus in vitro and inside epithelial cells as well as in an animal model of infection. Using the xyl/tetO promoter::gfp_uvr fusion carried on a shuttle …

Therapeutic Electromagnetic Field Effects On Angiogenesis And Tumor Growth, C. Douglas Williams, Marko S. Markov, W. Elaine Hardman, Ivan L. Cameron

Biochemistry and Microbiology

Background: A new approach to cancer therapy based on the application of therapeutic electromagnetic fields (TEMF) has been developed by EMF Therapeutics, Inc., Chattanooga, TN, USA. This study was designed to assess the effect of TEMF on tumor vascularization and growth of murine 16/C mammmary adenocarcinoma cells in C3H/HeJ mice.

Materials and Methods: Implanted tumors were allowed to grow for seven days until the tumor volume reached 100 mm3 before treatment was started. Mice (20 per control, 10 per EMF exposed group) received treatment (10 minutes per day with 0, 10 mT, 15 mT or 20 mT) with a 120 …

Association Of Viral Genome With Graft Loss In Children After Cardiac Transplantation., Girish S. Shirali, J Ni, R E. Chinnock, J K. Johnston, G L. Rosenthal, N E. Bowles, J A. Towbin

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: The survival of recipients of cardiac allografts is limited by rejection, lymphoproliferative disease, and coronary vasculopathy. The purpose of this study in children who had received heart transplants was to evaluate the cardiac allografts for myocardial viral infections and to determine whether the presence of viral genome in the myocardium correlates with rejection, coronary vasculopathy, or graft loss.

METHODS: We enrolled heart-transplant recipients 1 day to 18 years old who were undergoing evaluation for possible rejection and coronary vasculopathy. Endomyocardial-biopsy specimens were evaluated for evidence of rejection with the use of standard criteria and were analyzed for the presence …

Clumping Factor A Mediates Binding Of Staphylococcus Aureus To Human Platelets, Ian R. Siboo, Ambrose L. Cheung, Arnold S. Bayer, Paul M. Sullam

Dartmouth Scholarship

The direct binding of bacteria to platelets may be an important virulence mechanism in the pathogenesis of infective endocarditis. We have previously described Staphylococcus aureus strain PS12, a Tn551-derived mutant of strain ISP479, with reduced ability to bind human platelets in vitro. When tested in an animal model of endocarditis, the PS12 strain was less virulent than its parental strain, as measured by bacterial densities in endocardial vegetations and incidence of systemic embolization. We have now characterized the gene disrupted in PS12 and its function in platelet binding. DNA sequencing, Southern blotting, and PCR analysis indicate that PS12 contained two …

Sars, A Sara Homolog Repressible By Agr, Is An Activator Of Protein A Synthesis In Staphylococcus Aureus, Ambrose L. Cheung, Katherine Schmidt, Brian Bateman, Adhar C. Manna

Dartmouth Scholarship

The expression of protein A (spa) is repressed by global regulatory loci sarA and agr. Although SarA may directly bind to the spa promoter to downregulate spa expression, the mechanism by which agr represses spa expression is not clearly understood. In searching for SarA homologs in the partially released genome, we found a SarA homolog, encoding a 250-amino-acid protein designated SarS, upstream of the spa gene. The expression of sarS was almost undetectable in parental strain RN6390 but was highly expressed in agr and sarA mutants, strains normally expressing high level of protein A. Interestingly, protein A …

Characterization Of Sarr, A Modulator Of Sar Expression In Staphylococcus Aureus, Adhar Manna, Ambrose L. Cheung

Dartmouth Scholarship

The expression of virulence determinants in Staphylococcus aureus is controlled by global regulatory loci (e.g., sar and agr). The sar locus is composed of three overlapping transcripts (sar P1, P3, and P2 transcripts from P1, P3, and P2 promoters, respectively), all encoding the 372-bp sarA gene. The level of SarA, the major regulatory protein, is partially controlled by the differential activation of sar promoters. We previously partially purified a ∼12 kDa protein with a DNA-specific column

Health Professions Division Catalog Academic Year 2001-2002, Nova Southeastern University

Health Professions Divisions Course Catalogs and Course Descriptions

No abstract provided.

The Process Of Clinical Trials: A Model For Successful Clinical Trial Participation, Cecile A. Lengacher, Lois L. Gonzalez, Rosemary Giuliano, Mary P. Bennett, Charles E. Cox, Douglas S. Reintgen

Nursing Faculty Publications

No abstract provided.

Department Of Radiation Oncology And Kimmel Cancer Center, Thomas Jefferson University, The Intronic G13964c Variant In P53 Is Not A High-Risk Mutation In Familial Breast Cancer In Australia., Anna Marsh, Amanda B Spurdle, Bruce C Turner, Sian Fereday, Heather Thorne, Gulietta M Pupo, Graham J Mann, John L Hopper, Joseph F Sambrook, Georgia Chenevix-Trench

Department of Radiation Oncology Faculty Papers

BACKGROUND: Mutations in BRCA1 and BRCA2 account for approximately 50% of breast cancer families with more than four affected cases, whereas exonic mutations in p53, PTEN, CHK2 and ATM may account for a very small proportion. It was recently reported that an intronic variant of p53--G13964C--occurred in three out of 42 (7.1%) 'hereditary' breast cancer patients, but not in any of 171 'sporadic' breast cancer control individuals (P = 0.0003). If this relatively frequent occurrence of G13964C in familial breast cancer and absence in control individuals were confirmed, then this would suggest that the G13964C variant plays a role in …

Epstein-Barr Virus Serology In The Diagnosis Of Nasopharyngeal Carcinoma From Sarawak, Madeline Wong Mei Fong

Student Works (2000-2009)

The Epstein-Barr virus (EBV) is closely associated with nasopharyngcal carcinoma (NPC). The role(s) of EBV in NPC remains unclear but antibodies to two EBV proteins namely the viral capsid antigen (VCA) and early antigen (EA), are clinically useful diagnostic markers of NPC. The NPC scenario in Malaysia has been based on studies done on West Malaysian patients but not much has been described for NPC in Sarawak, East Malaysia. In this study, 164 NPC sera from newly histologically confirmed NPC patients were collected from the Radiotherapy Unit of Kuching General Hospital, Sarawak prior to radiotherapy. One hundred and forty seven …

A Noninvasive Test For Vesico-Ureteric Reflux In Children, R. A. Mevorach, B. Cilento, S. Zahorian, C. Badgett, R. Walker, A. Atala, S. Iannello, M. Meyer

Electrical & Computer Engineering Faculty Publications

Objective To report the development and testing of a device for the noninvasive diagnosis of vesico‐ureteric reflux (VUR) which avoids the need for urethral catheterization (currently required to reliably determine the presence of VUR), and which thus avoids the anxiety of parents and patients that causes many families to refuse such evaluation.

Patients and methods Fifty‐four children (49 girls and five boys, mean age 7.2 years, range 4–14) previously evaluated as having VUR volunteered to participate; no child was symptomatic at the time of the study. Refluxing units were known to be present by voiding cysto‐urethrography (within 1 year, mean …

Attachment Of Toxoplasma Gondii To A Specific Membrane Fraction Of Cho Cells, Chaitali Dutta, Jane Grimwood, Lloyd H. Kasper

Dartmouth Scholarship

We have observed previously that attachment of Toxoplasma gondii to synchronized host cells is considerably increased at the mid-S phase (4 h postrelease). Synchronized CHO host cells at the mid-S phase were fractionated by molecular weight, and the antigens were used to produce a panel of polyclonal mouse antisera. The polyclonal antisera raised against fraction 4 with molecular mass ranging approximately from 18 to 40 kDa significantly reduced attachment to mid-S-phase host cells. Immunofluorescence assays demonstrated strong reactivity to mid-S-phase host cells and identified a number of potential receptors on Western blots. These data indicate that there is a specific …

Lack Of Cd4+ T Cells Does Not Affect Induction Of Cd8+ T-Cell Immunity Against Encephalitozoon Cuniculi Infection, Magali Moretto, Lori Casciotti, Brigit Durell, Imtiaz A. Khan

Dartmouth Scholarship

Cell-mediated immunity has been reported to play an important role in defense against Encephalitozoon cuniculi infection. Previous studies from our laboratory have underlined the importance of cytotoxic CD8⁺ T lymphocytes (CTL) in survival of mice infected with E. cuniculi. In the present study, immune response against E. cuniculi infection in CD4⁺T-cell-deficient mice was evaluated. Similar to resistant wild-type animals, CD4^−/− mice were able to resolve E. cuniculi infection even at a very high challenge dose (5 × 10⁷ spores/mouse). Tissues from infected CD4^−/−mice did not exhibit higher parasite loads in comparison to …

Helicobacter Pylori Serology And The Diagnosis Of H. Pylori Infection In Children, Yoram Elitsur, Rafah Aflak, Cheryl Neace, W. E. Triest

Biochemistry and Microbiology

Serological screening accuracy rate may be dependent on clinical and pathological determinants. The aim of this study was to evaluate the accuracy of Hp serology test (Roche Biomedical Lab., Labcorp), In the diagnosis of Hp infection in 121 children who were seen in the Pediatric Gastoenterology Clinic at the Marshall University Joan C. Edwards School of Medicine In Huntington. Positive serology detected children with Hpassociated gastritis with a sensitivity of 51.6%. Positive serology significantly correlated with the degree of gastric inflammation and density of Hp organisms in the gastric mucosa (ANOVA p < 0.001). The Labcorp. Hp-ELISA test had a poor accuracy rate for the detection of Hp-gastritis in children. Gastric biopsies should always be performed to establish the diagnosis of Hp infection in children.

Low Serum Alpha 1 Antitrypsin In Duodenal Ulcer--A Family Study, Anjum Shahid, Sarwar J, Zuberi Mohammad A, Waqar,Huma Qureshi Waqar,Huma Qureshi Waqar,Huma Qureshi, Anwar Ali Siddiqui, Taranum Sultana

Department of Biological & Biomedical Sciences

No abstract provided.

Structured Treatment Interrupion (Sti) With Nevirapine (Nvp) And Two Nucleoside Reverse Transciptase Inhibitors (Nsrti): Is Re-Suppression Achieved Following Treatment Interruption?, Joseph L. Yozviak Do, Facp, R Eric Doerfler Np, Cch, William C. Woodward Do

Department of Medicine

No abstract provided.

Staphylococcus Aureus Rn6390 Replicates And Induces Apoptosis In A Pulmonary Epithelial Cell Line, Barbara C. Kahl, Mark Goulian, Willem Van Wamel, Mathias Herrmann, Sanford M. Simon, Gilla Kaplan, Georg Peters, Ambrose L. Cheung

Dartmouth Scholarship

Staphylococcus aureus frequently colonizes the airways of patients with compromised airway defenses (e.g., cystic fibrosis [CF] patients) for extended periods. Persistent and relapsing infections may be related to live S. aureus bacteria actively residing inside epithelial cells. In this study, we infected a respiratory epithelial cell line, which was derived from a CF patient, with S. aureus RN6390. Internalization of S. aureus was found to be time and dose dependent and could be blocked by cytochalasin D. Transmission electron microscopy revealed that internalized bacteria resided within endocytic vacuoles without any evidence of lysosomal fusion in a 24-h period. The results …

Antiretroviral Therapy (Art) In Clinical Practice: Effectiveness And Tolerability Of Necvirapine (Nvp), Stavudine (D4t) And Lamivudine (3tc), Joseph L. Yozviak Do, Facp, R Eric Doerfler Np, Cch, William C. Woodward Do

Department of Medicine

No abstract provided.

Differential Infectivity And Division Of Toxoplasma Gondii In Human Peripheral Blood Leukocytes, Jacqueline Y. Channon, Rosanne M. Seguin, Lloyd H. Kasper

Dartmouth Scholarship

When tachyzoites were incubated with human peripheral blood leukocytes in vitro, more monocytes and dendritic cells than neutrophils or lymphocytes were infected. Although tachyzoites were able to divide in each of these cell types, monocytes and dendritic cells were more permissive to rapid tachyzoite division than neutrophils or lymphocytes.

Vitamin A And Cancer, Richard M. Niles

Biochemistry and Microbiology

Vitamin A, its physiological metabolites and synthetic derivatives (retinoids) have been shown to have protective effects against the development of certain types of cancer. In addition, pharmacological amounts of retinoids have been used with some success in the treatment of a few human tumors. The chemoprevention effect of retinoids is most likely exerted at the tumor promotion phase of carcinogenesis. Retinoids block tumor promotion by either inhibiting proliferation, inducing apoptosis, inducing differentiation, or a combination of these actions. Clinically, isotretinoin (13-cis-retinoic acid) significantly decreases the incidence of second primary tumors in patients with head and neck cancer and also reduces …

Effects Of Estradiol And Progesterone On Susceptibility And Early Immune Responses To Chlamydia Trachomatis Infection In The Female Reproductive Tract, Charu Kaushic, Fan Zhou, Andrew D. Murdin, Charles R. Wira

Dartmouth Scholarship

We have used a previously described rodent model to examine the influence of hormonal environment on susceptibility and immune responses to genital Chlamydia infection. Ovariectomized rats were administered estradiol, progesterone, or a combination of both, infected with Chlamydia trachomatis via the intrauterine route, and sacrificed 5 days later. Histopathological examination showed severe inflammation in the uteri and vaginae of progesterone-treated animals, whereas animals receiving estradiol or a combination of both hormones showed no inflammation. Large numbers of chlamydiae were found in vaginal secretions of progesterone-treated and combination-treated animals, while estradiol-treated animals had none. Tissue localization showed that numerous chlamydial inclusions …

Antiretroviral Therapy (Art) In Clinical Practice: Ethnic Variability In Effectiveness And Tolerability Of Nelfinavir And Two Nucleoside Reverse Transcriptase Inhibitors, Joseph L. Yozviak Do, Facp, B Moran, R Eric Doerfler Np, Cch, William C. Woodward Do

Department of Medicine

No abstract provided.

Angiotensin Ii Promotes Atherosclerotic Lesions And Aneurysms In Apolipoprotein E-Deficient Mice, Alan Daugherty, Michael W. Manning, Lisa A. Cassis

Gill Heart & Vascular Institute Faculty Publications

Increased plasma concentrations of angiotension II (Ang II) have been implicated in atherogenesis. To examine this relationship directly, we infused Ang II or vehicle for 1 month via osmotic minipumps into mature apoE^–/– mice. These doses of Ang II did not alter arterial blood pressure, body weight, serum cholesterol concentrations, or distribution of lipoprotein cholesterol. However, Ang II infusions promoted an increased severity of aortic atherosclerotic lesions. These Ang II–induced lesions were predominantly lipid-laden macrophages and lymphocytes; moreover, Ang II promoted a marked increase in the number of macrophages present in the adventitial tissue underlying lesions. Unexpectedly, pronounced abdominal …

Effect Of Receptor-Selective Retinoids On Growth And Differentiation Pathways In Mouse Melanoma Cells, Sejal H. Desai, Goran Boskovic, Linda L. Eastham, Marcia Dawson, Richard M. Niles

Biochemistry and Microbiology

Treatment of B16 mouse melanoma cells with all-trans-retinoic acid (ATRA) results in inhibition of cell proliferation and induction of differentiation. Accompanying these events is an induction of retinoic acid receptor β (RARβ) expression, an increase in protein kinase Cα (PKCα) expression, and enhanced activator protein-1 (AP-1) transcriptional activity. These cells express nuclear RARα and RARγ and nuclear retinoid X receptors (RXR) α and β constitutively. We tested the ability of receptor-selective retinoids to induce the biochemical changes found in ATRA-treated melanoma cells and also tested their effectiveness in decreasing anchorage-dependent and -independent growth. The RXR-selective ligand (2E,4E)-6-(5,6,7,8-tetrahydro-3,5,5,8,8-pentamethyl-2-naphthalenyl)-3,7-dimethyl-2,4,6-octatrienoic acid (SR11246) was …

Is Incapacity A Permanent Thing?, Shirley M. Neitch

Internal Medicine

No abstract provided.

Differential Expression Of Chemokines In A Mouse Model Of Wound Healing, Susan H. Jackman, Matthew B. Yoak, Shivaleela Keerthy, Bonnie L. Beaver

Biochemistry and Microbiology

Macrophages have a multifaceted role in wound healing. While their initial activity may be in the degradation and elimination of damaged tissue, macrophages also produce and secrete a variety of mediators that can participate in the repair process as well. To perform these functions, macrophages must be recruited to a wound site. Our purpose was to examine the temporal and spatial expression of macrophage chemoattracting cytokines (chemokines) at a surgical wound site. A surgical wound was prepared on the dorsal aspect of B6AFI/J mice. Biopsies were obtained from the wound and a comparable nonwounded area between 6 and 72 hr …

Dietary Fish Oil Sensitizes A549 Lung Xenografts To Doxorubicin Chemotherapy, W. Elaine Hardman, Mary Pat Moyer, Ivan L. Cameron

Biochemistry and Microbiology

A549 xenografts were allowed to grow in nude mice to about 5 mm in diameter, then diets were changed to modified AIN-76 diets containing 19% wt/wt. fish oil (FO) or 20% wt./wt. com oil (CO). Ten days later dietary ferric citrate (0.3% wt./dry wt.) was added and doxoribicin (DOX) treatment (3.6 mg/kg i.v. each of the 5 days for 18 days) commenced. Treatment with DOX halted the growth of tumors in the CO fed mice. However, in those mice, which consumed FO or FO with ferric citrate, treatment with DOX caused significant tumor regression.