Digital Commons Network^™

Enhancement Of Anti-Hiv-1 Ribozyme Activities By Rev Binding And Multimerization, Yuksel Yildiz

Loma Linda University Electronic Theses, Dissertations & Projects

To effectively apply hammerhead ribozymes as therapeutic agents it is necessary to co-localize them with the desired target. Human immunodeficiency virus type1 (HIV- 1) infectivity is dependent on env gene expression. HIV-1 Rev protein binds to a higher ordered RNA structure within the env transcript termed the Rev Binding Element (RBE). In anti-HIV gene therapy employing ribozymes to increase the co-localization of anti- HIV ribozymes with target HIV mRNAs, it has been proposed that when the native HIV- 1 RBE is appended to a ribozyme as a decoy molecule, simultaneous binding of Rev monomers to the RBE sequences in both …

Cd8+-T-Cell Immunity Against Toxoplasma Gondii Can Be Induced But Not Maintained In Mice Lacking Conventional Cd4+ T Cells, Lori Casciotti, Kenneth H. Ely, Martha E. Williams, Imtiaz A. Khan

Dartmouth Scholarship

T-cell immunity is critical for survival of hosts infected with Toxoplasma gondii. Among the cells in the T-cell population, CD8⁺ T cells are considered the major effector cells against this parasite. It is believed that CD4⁺ T cells may be crucial for induction of the CD8⁺-T-cell response against T. gondii. In the present study, CD4^−/− mice were used to evaluate the role of conventional CD4⁺ T cells in the immune response against T. gondii infection. CD4^−/− mice infected with T. gondii exhibited lower gamma interferon (IFN-γ) messages in the majority of their …

The Utilization Of Services Of Health Care Providers Among Patients Presenting To Family Physicians At A Teaching Hospital In Karachi, Pakistan, Waris Qidwai, Iqbal Azam, S. S. Ali, S. Ayub

Department of Family Medicine

Objective: To study the utilization of services of Health care providers among patients presenting to Family Physicians in a teaching hospital in Karachi.
Methodology: It was a cross sectional study. A questionnaire was developed to collect patient’s utilization of services of health care providers. The investigators administered the questionnaire to 387 patients, after purpose of the study was explained, written consent was taken and confidentiality was assured.
Results: The study population included more females than males, with average age of 32.6 years. The majority were married, well educated, in private and government service, were students or housewives. …

Factors Influencing Immunization Status In Primary Care Clinics, David Page, Jan Meires, Amy B. Dailey

Health Sciences Faculty Publications

Background and Objectives: National standards and goals for childhood immunization rates are well established. Yet, despite clear standards and goals, physicians do not achieve the desired rate (90%) for immunization coverage. This study examined factors related to immunization status for 2-year-old children in pediatric and family practice settings.

Methods: Specially trained personnel used computer software to audit 2,552 records from 42 practices in Northeast Florida throughout 1997–1999. Immunization records were judged as either complete or incomplete, and factors related to immunization status were studied. Clinic type and 18 immunization practice standards were reviewed for effect on immunization status.

Results: The …

Primaquine-Induced Hemolytic Anemia: Formation And Mechanism Of Action Of The Hemotoxic Metabolite 6-Methoxy-8-Hudroxylamoniquinoline (Maq-Noh), Laura Jane Campbell-Bolchoz

MUSC Theses and Dissertations

Primaquine is an important antimalarial drug that is often dose-limited in therapy by the onset of hemolytic anemia. It is well accepted that this toxicity is due to the action of its metabolites and not the parent compound. However, the toxic species have not been identified and little is known about the mechanism underlying primaquine-induced red cell injury. Previous studies to identify the hemotoxic metabolites have focused on the redox active phenolic derivatives of primaquine and have shown that a number of these compounds are capable of decreasing red cell GSH levels and oxidizing oxyhemoglobin to methemoglobin. However, these derivatives …

Small Glutamine-Rich Protein/Viral Protein U–Binding Protein Is A Novel Cochaperone That Affects Heat Shock Protein 70 Activity, Peter C. Angeletti, Doriann Walker, Antonito T. Panganiban

Nebraska Center for Virology: Faculty Publications

Molecular chaperone complexes containing heat shock protein (Hsp) 70 and Hsp90 are regulated by cochaperones, including a subclass of regulators, such as Hsp70 interacting protein (Hip), C-terminus of Hsp70 interacting protein (CHIP), and Hsp70-Hsp90 organizing factor (Hop), that contain tetratricopeptide repeats (TPRs), where Hsp70 refers to Hsp70 and its nearly identical constitutive counterpart, Hsc70, together. These proteins interact with the Hsp70 to regulate adenosine triphosphatase (ATPase) and folding activities or to generate the chaperone complex. Here we provide evidence that small glutamine-rich protein/viral protein U–binding protein (SGT/UBP) is a cochaperone that negatively regulates Hsp70. By “Far-Western” and pull-down assays, SGT/UBP …

Effect Of Zinc On The Treatment Of Plasmodium Falciparum Malaria In Children: A Randomized Controlled Trial, F. Sempertegui, B. Estrella, F.R. Toapanta, D.S. Torres, D.E. Calahorrano, K. Yeboah-Antwi, E. Addo-Yobo, P. Arthur, S. Newton, Zul Premji, M. Hubert, C.S. Makwaya, F. Ssengooba, J. Konde-Lule, E. Mukisa, D.H. Hamer, W. Macleod, C. Duggan, W. Fawzi, J. Simon, V. Mwanakasale, M. Mulenga, T. Sukwa, J. Tshiula

Pathology, East Africa

Background: Zinc supplementation in young children has been associated with reductions in the incidence and severity of diarrheal diseases, acute respiratory infections, and malaria.

Objective: The objective was to evaluate the potential role of zinc as an adjunct in the treatment of acute, uncomplicated falciparum malaria; a multicenter, double-blind, randomized placebo-controlled clinical trial was undertaken.

Design: Children (n = 1087) aged 6 mo to 5 y were enrolled at sites in Ecuador, Ghana, Tanzania, Uganda, and Zambia. Children with fever and ≥ 2000 asexual forms of Plasmodium falciparum/μL in a thick blood smear received chloroquine and were randomly assigned to …

Lack Of Benefit Of Granulocyte Macrophage Or Granulocyte Colony Stimulating Factor In Patients With Febrile Neutropenia, T. Siddiqui, I. A. Burney, A. Salam, G. N. Kakepoto, Mohammad Khurshid, R. A. Smego

Section of Haematology/Oncology

Objectives: To compare the clinical benefits of granulocyte-colony stimulating factor (G-CSF) or granulocyte macrophage-colony stimulating factor (GM-CSF) plus standard supportive care to supportive care alone among cancer patients with febrile neutropenia.
Methods: Clinical data were collected retrospectively from 148 consecutive cancer patients with neutropenia and fever. Patients had hematologic (i.e., acute leukemias or lymphoproliferative disorders) or non-hematologic malignancies (i.e., solid tumors including carcinoma of breast, lung, or colon). Clinical variables analyzed included: age and sex; underlying malignancies; chemotherapy regimens; symptoms at time of presentation; duration of fever prior to study enrollment; days from chemotherapy until administration of GM-CSF or …

Prevalence And Risk Factors For Vaginal Candida Colonization In Women With Type 1 And Type 2 Diabetes, Ella M. De Leon, Scott J. Jacober, Jack D. Sobel, Betsy Foxman

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Diabetes mellitus increases the rate of vaginal colonization and infection with Candida species

Methods

We surveyed women with diabetes receiving care at either an urban or suburban diabetes clinic to examine the relationship between vaginal Candida colonization, diabetes type and duration, and HbA_1c level. 101 participants completed the self-administered questionnaire and self-collected a vaginal swab for Candida culture. Candida colonization was similar by age and race.

Results

Type 1 diabetics were three times as likely as type 2 diabetics to be colonized with any Candida species (OR = 3.4; 95% CI: 1.03, 11.41; p = 0.04); even …

Abscesses In The Liver: Amoebic Or Pyogenic?, Bushra Jamil, Saeed Hamid

Department of Medicine

No abstract provided.

Staphylococcus Aureus Agr And Sara Functions Are Required For Invasive Infection But Not Inflammatory Responses In The Lung, Geoffrey Heyer, Shahryar Saba, Robert Adamo, William Rush, Grace Soong, Ambrose Cheung, Alice Prince

Dartmouth Scholarship

Staphylococcus aureus strains lacking agr- and sarA-dependent gene products or specific MSCRAMM (microbial surface components recognizing adhesive matrix molecules) adhesins were compared for the ability to activate inflammatory responses in the lung. The mutants were evaluated for virulence in a mouse model of pneumonia and by quantifying their ability to stimulate interleukin-8 (IL-8) and granulocyte-macrophage colony-stimulating factor (GM-CSF) expression in respiratory epithelial cells. In a neonatal mouse, only strains with intact agr and sarA loci were consistently associated with invasive, fatal pulmonary infection (P < 0.001) and sarA was specifically required to cause bacteremia (P < 0.001). The agr and/or sarA mutants were, nonetheless, fully capable of producing pneumonia and were as proficient as the wild-type strain in stimulating epithelial IL-8 expression, a polymorphonuclear leukocyte chemokine, in airway cells. In contrast, agr and especially sarA mutants induced less epithelial GM-CSF expression, and MSCRAMM mutants lacking fibronectin binding proteins or clumping factor A, a ligand for fibrinogen, were unable to stimulate epithelial GM-CSF production. The ability to induce IL-8 expression was independent of the adherence properties of intact bacteria, indicating that shed and/or secreted bacterial components activate epithelial responses. While conserved staphylococcal components such as peptidoglycan are sufficient to evoke inflammation and cause pneumonia, the agr and sarA loci of S. aureus are critical for the coordination of invasive infection of the lungs.

General Practitioners' Attitudes To Palliative Care : A Regional Perspective, Richelle Lee-Steere

Theses : Honours

The study explores regional general practitioners' attitudes to palliative care through semi- structured interviewing using a qualitative methodology. Attitudes to palliative care were examined using the general practitioners' accounts of their experiences and perceptions of caring for terminally ill patients. The participants were ten registered general practitioners located within the Greater Sunbury Division of General Practice in the South West of Western Australia. A semi-structured interview schedule containing ten open-ended questions was used to assess regional general practitioners' attitudes to palliative care. Examples of the research questions included: What are regional general practitioners' attitudes to palliative care? What supports are …

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 …

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 …

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 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 …

Vital Signs, Fall 2001, Boonshoft School Of Medicine

Vital Signs

A twenty three page newsletter created by the Boonshoft School of Medicine to document the current affairs of the school. This issue includes a variety of feature articles, alumni profiles, class notes, and more.

Bilateral Cervical Radiculopathy As A Presentation Of Spinal Tuberculosis: Report Of Two Cases, G R. Sharma, Rashid Jooma

Section of Neurosurgery

No abstract provided.

Commencement, Philadelphia (2001), Philadelphia College Of Osteopathic Medicine

Commencements

Philadelphia Campus D.O. Commencement Program, 110th Class. Degrees include Doctor of Osteopathic Medicine.

Commencement Speaker: The Honorable Ruth Ann Minner, Governor of Delaware

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 …

Vital Signs, Spring 2001, Boonshoft School Of Medicine

Vital Signs

A twenty-one page newsletter created by the Boonshoft School of Medicine to document the current affairs of the school. This issue includes feature articles, student notes, and more.

Maternal Deaths In A Developing Country: A Study From The Aga Khan University Hospital, Karachi, Pakistan 1988-1999, R N. Qureshi, S Jaleel, R Hamid, S F. Lakha

Department of Obstetrics & Gynaecology

Objective: The maternal deaths occurring over a twelve-year period (1988-1999) in a tertiary referral center were reviewed. The purpose of the study was to assess the causes of these maternal deaths.
Setting: The Aga Khan University Hospital (AKUH) Karachi, Pakistan.
Methods: The medical records of maternal deaths were reviewed. These were women who had either registered for delivery at the hospital; or were referred from another hospital or from home, when an emergency developed. They were either admitted to the Medicine, Surgery and the Obstetrics and Gynaecology Departments at the hospital.Results: A total of 81 maternal deaths were identified, of …

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

An Analysis Of Anemia And Child Mortality, B.J. Brabin, Zul Premji, F. Verhoeff

Pathology, East Africa

The relationship of anemia as a risk factor for child mortality was analyzed by using cross-sectional, longitudinal and case-control studies, and randomized trials. Five methods of estimation were adopted: 1) the proportion of child deaths attributable to anemia; 2) the proportion of anemic children who die in hospital studies; 3) the population-attributable risk of child mortality due to anemia; 4) survival analyses of mortality in anemic children; and 5) cause-specific anemia-related child mortality. Most of the data available were hospital based. For children aged 0-5 y the percentage of deaths due to anemia was comparable for reports from highly malarious …

Reovirus 1/L As A Model To Study The Induction Of Optimal Immunity At Mucosal And Systemic Sites, Sherry Renee Crowe

MUSC Theses and Dissertations

Achieving protective immunity at mucosal sites is critically important for effective immunization against pathogens that colonize the host via the wet epithelium. We utilized reovirus 1/L infection of mice to study immunization strategies for the induction of optimal humoral and cell-mediated immunity at mucosal surfaces. The humoral and cell-mediated responses at mucosal and systemic sites were monitored following upper respiratory tract, or systemic inoculation. Utilizing these models, we found that the combined upper and lower respiratory tract inoculation resulted in optimal humoral immunity proximally (in the respiratory tract), distrally (in the oral, gastrointestinal, and urogenital tracts), and systematically. This immune …

Reproductive Tract Infections: A Guide For Programme Managers, Sarah Hawkes, Anjali Nayyar, Johannes Van Dam, Kevin R. O'Reilly, Bidia Deperthes, Dinesh Agarwal

Reproductive Health

Reproductive tract infections (RTIs) including sexually transmitted infections represent a silent worldwide pandemic that adversely impacts the reproductive health (RH) of women and men. Various community- and hospital-based studies in India have provided insights into the magnitude of the problem. The International Conference on Population and Development (1994) emphasized integration of RH services to meet the needs of men and women especially with prevention and management of RTIs/STIs. The emergence of HIV and the identification of STIs as a risk factor for the spread of HIV have further lent a sense of urgency for a programmatic response to address this …

Female Genital Tuberculosis Revisted, R N. Qureshi, S Samad, R Hamid, S F. Lakha

Department of Obstetrics & Gynaecology

Objective: To assess the clinical presentation of genital tuberculosis and to study various modes of diagnosis and treatment.SETTING: The Aga Khan University Hospital (AKUH), Karachi.
Method: A retrospective case review of all index female cases of genital tuberculosis, admitted to AKUH over twelve years of period.
Result: A total of 40 cases of genital tuberculosis were reported during this time period. Majority of cases were between 25-45 years. The commonest presenting symptoms were infertility (42.5%) and abdominal pain (42%). Others included fever, ascites, irregular vaginal bleeding, oligomenorrhea, chest pain and pain in the flanks. Main mode of treatment was antituberculous …

Anatomical Variations Of Internal Jugular Vein As Seen By "Site Rite Ii" Ultrasound Machine--An Initial Experience In Pakistani Population, Hameedullah, M. A. Rauf, Fazal Hameed Khan

Department of Anaesthesia

Objective: To determine the anatomical variations of the internal jugular vein (IJV) in Pakistani adult population with the help of Site Rite II ultrasound machine.
Material and Method: The right IJV relation to the carotid artery was visualized at four different landmarks (angle of the mandible, thyroid cartilage, cricoid cartilage, and the supraclavicular area). Size of IJV in comparison to carotid artery was also seen.
Results: In 49 cases the IJV was found in aberrant relation to carotid artery at the angle of the mandible (p value
Conclusion:Care should be taken while cannulating IJV at the angle of the …

Acute Haemolysis In Childhood Falciparum Malaria, H. Ekvall, P. Arese, F. Turrini, K. Ayi, F. Mannu, Zul Premji, A. Bjorkman

Pathology, East Africa

Acute haemolysis associated with clinical episodes of high-level Plasmodium falciparum parasitaemia was studied in 20 children from an holoendemic area (coastal Tanzania). The change in blood haemoglobin (Hb) concentration ranged from -46 to +5 g/L during the 72-h observation period and was linearly related to maximum parasitaemia. Balance studies between loss of blood Hb, increase in plasma Hb and appearance of Hb in the urine indicated that extravascular clearance of red cells was the predominant mode of erythrocyte clearance. Most subjects, however, showed minor signs of intravascular haemolysis. The plasma Hb was ≪1% of blood Hb and haemoglobinuria was detected …