Chamberlin
Huang
Sardelis
Claborn Jones-Trower
Skvorc
DiCarlo
Kluchinsky
Storey
Ettenberg
Ross Waterhouse
Grieco
Judith Chamberlin
Department of Preventive Medicine and Biometrics
Doctor of
Public Health
2001
Major Advisor:
Larry W. Laughlin, M.D., Ph.D.
Department of Preventive Medicine and Biometrics
Thesis Title: The Epidemiology of Bartonellosis in Peru
Abstract
Bartonellosis has caused debilitating illness and death since pre-Inca times. It is a vector-borne infectious disease found in the medically underserved communities of the high Andean mountain valleys of South America. The disease manifests in two clinical stages, a hematic stage followed by an eruptive stage. The etiologic agent is Bartonella bacilliformis, an alpha-2 proteobacteria that intracellularly infects erythrocytes and endothelial cells. Although recognized for centuries, relatively little is known about its epidemiology. This study examines the epidemiology and transmission dynamics of bartonellosis with the goal of developing a rationale control program.
In January 1997 a two year, population-based prospective cohort investigation was initiated in an area of Peru with endemic bartonellosis. Using house-to-house surveys, the population was censused, interviewed and then followed for evidence of bartonellosis. Active and passive case detection methods were used to identify cases and to determine prevalence, incidence, morbidity, mortality, and chronic carrier state. An indirect fluorescence antibody assay was developed to aid diagnosis. Individuals with clinical disease were enrolled in a cases-series investigation and re-evaluated every six months to determine the natural history of disease and the IgG antibody response over time. Case-houses were mapped using geographic information systems (GIS) to determine any possible spatial patterns of disease. Changes in incidence as a function of average monthly precipitation and temperature were analyzed using climatic data obtained from the National Centers for Environmental Prediction.
Of the 690 participants enrolled in the cohort investigation, 45% had IgG antibodies to B. bacilliformis. At enrollment, 0.5% of participants had asymptomatic bacteremia. After two years of follow-up, the incidence rate was 12.7 per 100 person-years. Significant risk factors for infection included young age and living in the household of another case; 70% of the cases were clustered in 18% of the households, and 75% of the cases occurred during the 1998 "El Nino", a period when average temperatures and precipitation levels increased. The 292 participants in the case-series investigation had a case fatality rate of 6%. Of those participants who were followed, 10% had persistent bacteremia after therapy, 41% experienced continual symptoms, and within 12 months, 44% of first stage clinical cases progressed to the second clinical stage with cutaneous lesions. IgG antibodies provided little protection from continual symptoms; participant's antibody titers slowly reverted to negative at a rate of 3% per year. The quantity and character of bartonellosis in this community represents a significant public health problem. Efforts to reduce disease prevalence should focus both on host and environmental factors and on methods to more effectively eradicate bacteremia in infected individuals.
LCDR David Merrell Claborn, USN
Department of Preventive Medicine and Biometrics
Doctor of
Public Health
2001
Major Advisor: Richard G. Andre, Ph.D., Department of Preventive Medicine and Biometrics
Thesis Title: Remote Sensing and Geographic Information Systems as Decision Support Tools for Malaria Control in the Republic of Korea
Abstract
Cost-comparisons are a necessary component of decision-making in the control of vector-borne disease. Remote sensing and geographical information systems (GIS) were used to estimate the size of vector larval habitats to allow a cost comparison of chemoprophylaxis and larviciding, two malaria control methods currently being considered for use in the Republic of Korea (ROK).
Two U.S. Army camps (Cp Casey and Cp Greaves) were selected as research sites. The cost of chemoprophylaxis was estimated for each population assuming a 19-week treatment regimen consisting weekly chloroquine chemoprophylaxis with terminal primaquine treatment, a single pre-treatment G-6-PD deficiency test, and a 50% turnover in personnel during the malaria transmission season. Annual cost of chemoprophylaxis was $37.53/person.
Larval habitats were sampled from June through September, 2000. Anopheline larvae were reared to the adult stage and identified using adult and pupal morphological characteristics. Gene sequencing and random amplification of polymorphic DNA (RAPD) analyses were performed to confirm the identification of the mosquitoes. Both molecular work and pupal morphology indicated that most of the anophelines collected during the study were Anopheles sinensis Wiedemann and that the abundance of other anopheline species is generally overestimated by adult keys.
The size of vector larval habitats within the 1-km flight range of An. sinensis around the two U.S. Army camps was determined using satellite-acquired images, and the cost of treating those areas with an insect-growth regulator was estimated. At Cp Greaves, the cost of the requisite three larvicidal applications exceeded the cost of chemoprophylaxis by a factor of four, but at Cp Casey, chemoprophylaxis was about 21 times as expensive as larviciding due to the larger number of at-risk personnel and the smaller size of the vector habitats.
This study demonstrates the usefulness of remote sensing and GIS as decision support tools for estimating costs of vector control methods used in the control of vector-borne disease. Such information can then serve as one component of the decision-making process for the design and implementation of disease prevention strategies.
Key Words (Indexing): Anopheles sinensis, Anopheles lesteri, Anopheles yatsushiroensis, malaria, Plasmodium vivax, remote sensing, larviciding, chemoprophylaxis, cost- comparison.
LTC Cheryl
D. DiCarlo, U.S.A.
Department of Anatomy, Physiology and Genetics
Doctor of
Philosophy
2001
Major Advisor: Diane Borst, Ph.D., Department of Anatomy, Physiology & Genetics
Thesis Title: Cataracts in the Fat Sand Rat: An Ocular Complication of Diabetes
ABSTRACT
Purpose: The fat sand rat, Psammomys obesus, a spontaneous model for Type 2 diabetes, develops cataracts within days of the onset of clinical diabetes. The purpose of this research was to determine the crystallin composition of the normal sand rat lens and determine the changes that occur during diabetic cataract formation.
Materials and Methods: Slit-lamp biomicroscopy was used for ocular examinations. Blood glucose, glycated hemoglobin (HbA1c), aqueous glucose, vitreous glucose, vitreous glycated protein and lens extract glycated protein and protein values were determined using standard techniques and colorimetric test kits. Location of glucose transporter (GLUT) transcripts was determined using reverse transcriptase polymerase chain reaction (rtPCR). Lens extracts were prepared then separated by gel filtration chromatography to study the crystallin classes by SDS-PAGE. Western blotting and mass spectrometry were used to verify the crystallin composition.
Results: Blood glucose, aqueous glucose, vitreous glucose and glycated hemoglobin (HbA1c) levels were all significantly elevated in the diabetic sand rats. Water-soluble protein levels were higher in the control sand rats. No significant differences were seen among glycated protein levels of the lens extracts. GLUT1, GLUT3 and GLUT4 transcripts were present in the anterior epithelial cells of the lens but only the GLUT 4 transcript was present in the lens fiber cells. SDS-PAGE of the diabetic animals revealed an increased banding pattern at 35 - 42 kDa and a band shift from 22.5 to 23.5 kDa. Western blotting and mass spectrometry confirmed "-A crystallin aggregates and $2B/$B3 crystallin band shifts, respectively.
Discussion: This is the first report of characterization of the normal and cataractous lens in the fat sand rat. The elevated glucose and HbA1c values in the blood of diabetic sand rats result in high levels of glucose within the eye. In the diabetics, there are "A crystallin aggregates and $B2/$B3 crystallin ratio shifts with cataracts. The diabetic cataracts seen on the slit-lamp exam are similar to those seen in humans. The data reported here provides the groundwork for medical therapies aimed at reversal or prevention of diabetic cataracts instead of surgical alleviation of this common cause of blindness. The sand rat is an excellent choice for such diabetes research.
Seth Ettenberg
Molecular and Cell Biology
Doctor of
Philosophy
2001
Major Advisor: Stan Lipkowitz, M.D., Ph.D. Molecular and Cell Biology Program
Title of Thesis: Regulation of Epidermal Growth Factor Receptor Signaling by chi-b
Abstract
Negative regulation of the Epidermal Growth Factor Receptor (EGFR) signaling is essential to proper regulation of cellular function. Genetic evidence from C. elegans and Drosophila melanogaster has demonstrated that cbl proteins are negative regulators of the EGFR in these organisms. To determine the role of mammalian cbl proteins in EGFR signaling, stable clones overexpressing cbl-b were created in two cell lines which have distinct biological responses to EGFR activation. In the 32D/EGFR murine hematopoetic cell line, overexpression of cbl-b inhibits Epidermal Growth Factor- induced (EGF) proliferation. In the MDA-MB-468 human breast cancer cell line, EGFR activation induces apoptosis. Overexpression of cbl-b in these cells inhibits EGF-induced-apoptosis. These data demonstrate that the mammalian cbl-b protein, like the C. elegans and Drosophila homologs, inhibits EGFR function. The molecular basis of this inhibition was studied in these two model systems. cbl-b is phosphorylated and recruited to the EGFR upon activation. In both cell lines, activation of the EGFR and activation of multiple downstream pathways have a shortened duration of signaling when cbl-b is overexpressed. Further biochemical analysis demonstrated that cbl-b increased activation-induced downregulation of the EGFR by enhancing EGFR ubiquitination and EGFR degradation. Specific inhibitors of either lysosomal or proteasomal proteases blocked cbl-b mediated EGFR degradation. Further analysis of cbl-b expression after cells are stimulated with EGF demonstrated that cbl-b is coordinately degraded along with the EGFR. Both EGFR and cbl-b downregulation requires an intact Tyrosine Kinase Binding and RING finger domain of the cbl-b protein. Additionally, binding of cbl-b to the EGFR is required for either protein to undergo EGF-induced degradation. Other proteins which are recruited to the activated EGFR complex are also coordinately degraded with the EGFR and cbl-b. These data allow us to construct a model of the regulation of the EGFR by cbl-b. Upon activation of the EGFR, cbl-b is phosphorylated and recruited to the EGFR. Next cbl-b enhances ubiquitination and subsequent degradation of the EGFR and other proteins bound to it. Finally, these data demonstrate that the mammalian protein cbl-b, like the C. elegans and Drosophila homologs, inhibits EGFR function.
John Paul
Grieco
Department of Preventive Medicine and Biometrics
Doctor of
Philosophy
2001
Major Advisor: Donald R. Roberts, Department of Preventive Medicine and Biometrics
Thesis Title: The bionomics and vector competence of Anopheles albimanus Weidemann and Anopheles vestitipennis Dyar and Knab (Diptera: Culicidae) in southern Belize, Central America
ABSTRACT
During an 18 month study period (1997-1998) in the Toledo District, southern Belize, a series of studies were undertaken to evaluate the vector competence of the Anopheles mosquitoes. At both Golden Stream and Rancho, the population densities of An. vestitipennis showed positive correlation with human cases of P. Vivax. and tested positive for P. Vivax. 210 (MFIR of 0.01 and MFIR of 0.0004, respectively). Population densities of An. darlingi from Golden Stream showed a negative correlation with high numbers of malaria cases but also tested positive for P. Vivax. 210 (MFIR of 0.001). Population abundance of An. albimanus from Rancho showed a negative correlation with malaria transmission and was not found naturally infected with malaria parasites. The feeding preference study showed An. vestitipennis to prefer feeding on human blood while An. albimanus showed a strong tendency for feeding on cattle and non-human hosts.
Human landing collections showed An. albimanus exhibited a bimodal biting pattern with an 0:1 ratio of 1 :0.1. Anopheles vestitipennis , however, exhibited a high level of biting activity throughout the night and a strong endophagic behavior (0:1 ratio of I :0.9). Post spray, deltamethrin functioned primarily as an irritant, causing premature exiting behavior. DDT exerted a powerful repellency effect resulting in a 97% post-spray reduction of An. vestitipennis females entering the hut.
Results from the comparative susceptibility study showed An. darlingi maintains a high salivary gland infection rate (41.0%) with P. falciparum (NF -54). Anopheles vestitipennis had a low salivary gland infection rate of9.3% with moderate numbers of sporozoites (i.e. 85.7% containing 50-250 sporozoites). Anopheles albimanus was the least susceptible to salivary gland infection (Golden Stream, 0.0% and Buena Vista, 2.2%).
Although the rate of infection for An. vestitipennis is low, its strong endophagic and anthropophagic behaviors augment its overall vector potential. This species clearly demonstrates characteristics of an important vector of malaria in Belize. The opposite appears to be true of An. albimanus . A low infection rate and both exophagic/zoophagic behaviors reveal this species to be a poor vector of P. falciparum.
Key Words (Indexing): Anopheles albimanus, Anopheles vestitipennis , DDT, deltamethrin, comparative susceptibility, experimental huts, Belize.
Grant D. Huang
Department of Medical and Clinical Psychology
Doctor of
Philosophy
2001
Major Advisor: Michael Feuerstein, Ph.D., Department of Medical and Clinical Psychology
Thesis Title: Workplace Stressors and Musculoskeletal Symptoms: Examining the Combined Impact of Ergonomic and Work Organization Factors
ABSTRACT
Work-related musculoskeletal symptoms are a significant public health challenge that have been associated with ergonomic and occupational psychosocial (i.e., work organization) factors. However, research still needs to delineate the specific dimensions of work organization that pose risks to workers. It is also unclear whether workplace physical and psychosocial stressors have a combined effect for these symptoms. Individuals (n = 289) from a population (U.S. Marines Corps) known to have a high rate of clinic visits associated with low back and upper extremity disorders were given a questionnaire containing items on demographics, health behaviors, level of physical exertion at work, family and life stressors, ergonomic factors, and work organization. After identifying specific work organization variables related to scheduling, job design, management style, career concerns, organizational characteristics, and interpersonal factors, logistic regression analyses were conducted to determine risks for low back symptoms only, upper extremity (UE) symptoms only, or concurrent low back and upper extremity symptoms. The occurrence of low back symptoms was associated with: age (OR = 1.09); family conflict (OR = 1.30); exposure to ergonomic stressors (OR = 1.03); time pressure at work (OR = 1.18); and, interpersonal demands at work (OR = 0.73). Risks for UE symptoms were: family conflict (OR = 1.27); exposure to ergonomic stressors (OR = 1.02); and, time pressure at work (OR = 1.16). Risk factors for the occurrence of both low back and UE symptoms were: age (OR = 1.13); exposure to ergonomic exposures (OR = 1.04); greater levels of interpersonal demands at work (OR = 1.56), work-related cognitive demands (OR = 1.20), and cognitive uncertainty (OR = 1.22); and, lower levels of skill discretion (OR = 1.09). Among the different ergonomic and work organization combinations, the occurrence of either low back symptoms or upper extremity symptoms was associated with higher levels of both ergonomic stressors and time pressure (OR = 2.61 & 2.90, respectively). Higher levels of ergonomic stressors and lower levels of involvement in management decisions (OR = 2.50) as well as higher levels of ergonomic stressors and time pressure (OR = 2.21), cognitive demands (OR = 2.25), cognitive uncertainty (OR = 2.08), interpersonal demands (OR = 2.44), or positive organizational climate (i.e., greater perceived responsibility) (OR = 2.15) were all risks for cases with both low back and upper extremity symptoms. These findings indicate the importance of distinguishing specific aspects of work organization and the need to concurrently assess them in conjunction with ergonomic risk factors in future research. They also highlight the potential of workstation and job redesign, job stress management, and organization-based efforts that incorporate worker input/involvement in reducing the levels of ergonomic stressors and work demands associated with low back and upper extremity symptoms.
Agnes Y. Jones-Trower
Molecular and Cell Biology Program
Doctor of
Philosophy
2001
Major Advisor: Christopher C. Broder, Ph.D., Department of Microbiology and Immunology
Thesis Title: Characterization and Enhanced Processing of Soluble, Oligomeric gp140 Envelope Glycoproteins Derived from Human Immunodeficiency Virus Type-1 Primary Isolates
ABSTRACT
HIV-1 first interacts with host cells through its envelope glycoprotein (Env), the major target of neutralizing antibodies. The biologically relevant form of Env is an oligomer, both in its presentation to the immune system and in virus entry. Also, native Env is cleaved into its gp120 and gp41 non-covalently associated subunits. Env-based vaccines have thus far failed to efficiently generate broadly cross-reactive, neutralizing antibodies towards primary isolates. Possible explanations for their failure are either they were derived from laboratory-adapted strains or they have not preserved the conformational structures necessary to elicit broadly reactive responses. Producing a broadly effective Env-based vaccine is also potentially complicated by the existence of multiple HIV-1 genotypes. Here, I have constructed a panel of truncated env genes from primary isolates of several different HIV-1 clades. Recombinant vaccinia viruses expressing these genes produce a secreted Env known as gp140. These gp140s were characterized by sucrose density gradient centrifugation and size exclusion chromatography analyses to determine oligomeric status and degree of processing. While most processed gp140s dissociated to monomeric forms, there was evidence that certain isolates could retain gp120 in an oligomer. A large scale purification scheme was developed using lentil lectin affinity and size exclusion chromatographies to prepare gp140 oligomers. Pre- and post-production processing enhancers (furin and plasmin) were examined as means to bolster the amount of processed gp140, and reducible crosslinkers were employed to analyze the ability of processed gp140 to maintain oligomeric forms. The antigenic properties of the gp140s, both cleaved vs. uncleaved, and crosslinked vs. non-crosslinked, were analyzed by immunoprecipitation with a panel of well-characterized human and mouse antibodies. The purified, crosslinked, cleaved oligomers retained important epitopes and the ability to undergo receptor-induced conformational change as could uncleaved gp140. Finally, a novel antigen delivery system (Matrix III) was investigated where oligomeric gp140 was encapsulated and administered to animals. Analysis of these sera has indicated that Matrix III does not seem to alter the quantity or quality of elicited antibody. Taken together, these experiments have provided critical information and material towards testing a variety of oligomeric Env-based vaccine strategies for the prevention of HIV-1 infection.
Timothy A.
Kluchinsky, Jr
Department of Preventive Medicine and Biometrics
Doctor of
Public Health
2001
Major Advisor: Philip A. Smith, Ph.D. Department of Preventive Medicine and Biometrics
Identification of CS-Derived Compounds Formed During Heat Dispersion of CS Riot Control Agent and the Temperature Ranges Associated with Their Formation
Abstract
Background: Military, correctional officer, and law enforcement personnel, are routinely exposed to 2-chlorobenzylidenemalononitrile (CS) during combat training, chemical protective mask confidence training, and riot control operations training. The public may be involuntarily exposed during rioting or civil disturbances. The potential exists for CS to form new compounds when dispersed by means of oxidizer-supported combustion of a chemical fuel from inside a canister.
Objectives: Research objectives were to identify CS-derived compounds that may be relevant to the preservation of health among those exposed, and to explore the effect of temperature on their formation. In addition to the need to identify these compounds and to understand their toxicity, knowledge of the temperature ranges associated with their formation is also important. If CS-derived compounds produced during heat-dispersion of CS canisters prove to be a public health hazard, alternative dispersion methods may be warranted..
Specific Aims: Research aims were to report on the objectives discussed above, publish the analytical methods and instrumental techniques necessary to characterize CS-derived compounds, and explore conditions leading to their formation.
Study Design: Air samples collected during heat-dispersion of CS were analyzed using open tubular gas chromatography coupled to mass spectrometry and compared to known standards using spectral interpretation techniques guided by spectral library comparison. Additional analytical methods were employed to explore formation of select inorganic analytes. A tube furnace was used to explore the effect of temperature on formation of CS-derived compounds.
Results: Compounds observed in air sample filter extracts, in addition to CS included 2- chlorobenzaldehyde, 2-chlorobenzonitrile, quinoline, 2-chlorobenzylcyanide, 1,2- dicyanobenzene, 3-(2-chlorophenyl)propynenitrile, cis and trans isomers of 2- chlorocinnamonitrile, 2 ,2-dicyano-3-(2-chlorophenyl)oxirane, 2-chlorohydrocinnamonitrile, benzylidenemalononitrile, cis and trans isomers of 2-cyanocinnamonitrile, 2- chlorobenzylmalononitrile, 3-quinoline carbonitrile, 3-isoquinoline carbonitrile, 4- Chlorobenzylidenemalononitrile, hydrogen cyanide, and hydrogen chloride. Experimentation using a tube furnace showed that formation of most of the CS-derived compounds observed was temperature dependent. The results of this research support the need for future evaluation of exposure to potentially harmful CS-derived compounds. Control of such exposures through implementation of appropriate personal protective equipment or alternative delivery methods may be warranted.
Nicole R.
Ross
Neuroscience Program
Doctor of
Philosophy
2001
Major Advisor: Dr. Linda L. Porter, Department of Anatomy, Physiology and Genetics
Title: The Effects of Dopamine and Estrogen upon Cortical Parvalbumin Expression
Abstract
Estrogen plays a protective role in several neurologic disorders known to involve alterations in both the dopamine system and (gamma amino butyric acid containing) GABAergic neurons that contain parvalbumin. Two studies were conducted to identify the effects of estrogen and dopamine upon cortical parvalbumin expression. In the first study, organotypic slice cultures of the frontal cortex were prepared from male rats (postnatal age 2-3) and maintained for 14 days in serum-enriched medium or media containing either: dopamine, estrogen, or a combination of the two. In control slices, parvalbumin immunoreactive neurons were primarily clustered near cortical layer V. All treatment conditions increased the distribution of parvalbumin labeled neurons in layer VI and enhanced the maturation of dendritic measures of labeled neurons in the deep layers (V -VI). Both estrogen and the combination treatment induced similar alterations in the superficial cortical layers (II-III). In the second study, gonadectomy (male rats, postnatal age 2) induced long lasting decreased in the density of parvalbumin immunoreactive neurons throughout all cortical layers. Estrogen replacement restored parvalbumin expression to control levels in the superficial cortical layers only. Gonadectomy also increased dopaminergic neuron density in the substantia nigra, compacta and tyrosine hydroxylase fiber length in the cortex at 33 days postnatal. Estrogen replacement returned dopaminergic neuron density, but not cortical fiber length, to control levels. Neonatal 6- hydroxy dopamine (6-0HDA) lesions produced results in the cortex that were similar to those induced by gon,adectomy, regardless of the loss in dopaminergic neurons. Taken together, these fmdings indicate that estrogen alters cortical parvalbumin expression and cortical and subcortical dopaminergic systems.
Michael R.
Sardelis
Department of Preventive Medicine and Biometrics
Doctor of
Philosophy
2001
Major Advisor: Richard G. Andre, Ph.D., Department of Preventive Medicine and Biometrics
Thesis Title: Potential for Aedes albopictus and Ochlerotatus j.japonicus to change the field ecology of arboviruses of human health importance in the mid-Atlantic region of the United States
ABSTRACT
Aedes albopictus and Ochlerotatus J. japonicus are mosquitoes that have been recently introduced into the United States. Since their introduction, they have been implicated in the transmission of one or more of the arboviruses of principal public health importance in the mid-Atlantic region. To more fully understand the potential of Ae. albopictus and Oc. J. japonicus to be vectors of endemic arboviruses, field and laboratory studies were conducted to assess their distribution in the region and to determine their vector competence for arboviruses for which data are lacking.
Aedes albopictus, a mosquito found in virtually all counties of states in the southeastern United States, was found to be established as far north as south-central Pennsylvania. Ochlerotatus J. japonicus, a mosquito that is generally found in more northern climates within its native range, was found to be established as far south as Maryland, and its relative abundance in Frederick County, Maryland, was found to be comparable to or greater than that of other container- inhabiting mosquito species.
Laboratory studies showed that Oc. j. japonicus is a competent vector of West Nile (WN), St. Louis encephalitis (SLE), eastern equine encephalitis (EEE), and La Crosse (LAC) viruses. Estimated transmission rates for these viruses by Oc. J. japonicus and by known principal or suspected vector mosquito species were determined concurrently for comparison. Based on these comparisons, Oc. j. japonicus was a more efficient laboratory vector of WN virus than Culex quinquefasciatus, as efficient as Culex pipiens in transmitting SLE virus, a less efficient laboratory vector of EEE virus than Ae. albopictus, and as efficient as Aedes triseriatus in transmitting LAC virus. Additional studies indicated that the extrinsic incubation period (EIP) for WN and EEE virus in Oc. j. japonicus held at 26C was between 7-11 days and around 5 days for, respectively.
Experimental
transmission studies showed that North American (NA) strains of Ae. albopictus
were competent vectors of WN virus. Transmission rates varied among the NA
strains tested, ranging from 36-92%. The EIP for WN virus in Ae. albopictus
held at 26oC was estimated to be 10 days. In a study to evaluate vertical
transmission, no virus was recovered from >12,000 F1 progeny.
This study provided key information for implicating Ae. albopictus and Oc.
j. japonicus as vectors of arboviruses of public health importance. These
data, combined with the behavioral and other biological characteristics of
Ae. albopictus and Oc. j. japonicus, indicate that these two introduced species
could change the field ecology of arboviruses of human health importance in
the mid-Atlantic region of the United States.
Casey Skvorc
Department of Medical and Clinical Psychology
Doctor of
Philosophy
2001
Major Advisor: Neil E. Grunberg, Ph.D., Department of Medical and Clinical Psychology
Thesis Title: Perception of Personal Well-Being and Workers' Compensation Injuries in Federal Correctional Workers
ABSTRACT
Federal correctional workers are tasked with protecting society from felons convicted of federal crimes and remanded to the custody of the Attorney General for incarceration. The physical and psychological demands placed upon these workers are great, and these workers have greater risk factors for occupational injury and disease than do other federal law enforcement officers. This dissertation examines rates of occupational injuries for approximately 30,000 federal correctional workers with regard to the security level of the prison worked in, the occupation of the correctional worker, gender, and associated number of days away from work after an occupational injury. Also analyzed is a Perception of Personal Well-Being (PWB)instrument, part of a widely circulated self-report measure of physical and emotional well-being administered to federal correctional workers on a nationwide basis. It was hypothesized that security level, and occupation, would be related to higher levels of occupational injury, lower levels of PWB, and that higher security levels would be associated with significantly lower levels of perception of personal well-being. Security level is significantly related to rates of occupational injury, in that federal correctional workers at Minimum security institutions had lower odds for the occurrence of occupational injuries than all other security levels except the AdMax security level. Security level was not a significant predictor for aggregate perception of well-being. Correctional officers had higher rates of occupational injuries than non-correctional officers. Security level was not a significant predictor of aggregate measures of PWB. Correctional officers had higher aggregate scores of PWB than non-correctional officers. Males had higher injury rates per 100 staff than females, and correctional officers had higher injury rates per 100 staff than non-correctional officers. Staff working at minimum security prisons had lower rates of injury per 100 staff than all other security levels. Male staff had higher mean levels of COP days than female staff, and correctional officers had higher numbers of COP days than non-correctional officers. The North Central region had higher a higher injury rate per 100 staff of all the regions, and the lowest mean level of COP days after an injury of all the regions. Male staff had higher levels of PWB than female staff, and correctional officers had higher levels of PWB than non-correctional officer staff.
Captain Julie
M. Storey
Department of Medical and Clinical Psychology
Doctor of
Philosophy
2001
Major Advisor: Michael Feuerstein, Ph.D., Department of Medical and Clinical Psychology
Thesis Title: Job Stress Reactivity and Work-Related Musculoskeletal Symptoms
ABSTRACT
Research regarding risk factors and correlates of work-related upper extremity (WRUE) symptoms and disorders have identified important ergonomic, workplace psychosocial, and individual psychosocial factors in their etiology, exacerbation and maintenance. Elevated levels of job stress have been frequently reported in this population, and epidemiological studies indicate job stress is associated with symptom severity, functional limitations, and lost work time in individuals with a variety of work-related upper extremity disorders. Although plausible pathophysiologic mechanisms exist linking the stress response to WRUE symptoms, little is known about the specific effects of stress on potential musculoskeletal and sympathetic nervous system mediators and how they may impact WRUE symptoms. Additionally, it is unclear if workers with these difficulties respond differently to stressors than asymptomatic workers. The present study was an exploratory investigation designed to address four primary questions: 1) do individuals with WRUE symptoms report higher levels of job stress and ergonomic exposure than asymptomatic individuals; 2) do workers with WRUE symptoms respond with greater musculoskeletal, neuroendocrine, and psychological responses than asymptomatic workers; 3) can ergonomic, psychosocial and physiological variables significantly discriminate between symptomatic and asymptomatic workers; and, 4) if they can discriminate between the groups, are the discriminating factors associated with general and WRUE-specific clinical outcomes. Female computer-users (n = 30; 16 symptomatic and 14 asymptomatic controls matched for age, body mass index, and job type) completed self-report measures of general health status, symptoms job stress, and ergonomic exposure and kept a 2-week diary of stressful work events and symptoms. At the end of the two-week monitoring period, participants were exposed to a laboratory-based job stress recall task while bilateral forearm activity (extensor and flexor), blood pulse volume, salivary cortisol levels, and self-report measures of symptoms and distress were monitored. Analyses of the self-report and job stress diary data indicated no significant differences between the groups on the frequency or intensity of job stress. However, symptomatic workers reported significantly greater distress in response to their peak stress event. Psychophysiologic data indicated significant group main effects for heart rate and forearm flexor muscle activity, where symptomatic workers exhibited higher tonic heart rate and flexor activity across all time periods. No group main effects were observed for forearm extensor, salivary cortisol, distress or symptoms, and no significant group by period interactions were observed for any of the measures. Canonical discriminant function analyses revealed that ergonomic exposure and job/family stress and coping were relatively poor discriminators between the groups while psychophysiologic response to the job stress recall task and a multifactorial model combining significant discriminators from all three domains (i.e., percent of work time at a computer workstation, the Impact of Events Scale-Revised, nondominant flexor activity during the stressor period, and heart rate during the recovery period) were good discriminators between the groups, classifying 89% and 92.3% of the sample respectively. Stepwise multiple regression analyses indicated this multifactorial model accounted for a significant amount of the variance in WRUE-specific outcomes (i.e., self-reported UE pain, functional limitations, and UE symptom severity), but not general physical or mental health. Results suggest that important ergonomic, psychosocial and physiological differences exist between these groups, including potential tonic heart rate elevations, tonic forearm musculature hyperarousal, and a tendency to experience prolonged cognitive and behavioral consequences to stressful events. These differences not only discriminate between the two groups but also are also associated with WRUE-specific clinical outcomes. Theoretical implications as well as questions for future research are discussed.
Roseann Marie
Waterhouse
Department of Pathology
Doctor of
Philosophy
2001
Major Advisor: Gabriela Dveksler, Associate Professor, Department of Pathology
Thesis Title: Identification of the First Receptor for a Pregnancy Specific Glycoprotein. Tetraspanins find their Ligand
ABSTRACT
Pregnancy
specific glycoproteins (PSGs) are a family of secreted proteins produced by
the placenta, which have been shown to be essential for pregnancy success.
The ability of human PSGs to induce anti-inflammatory cytokines has led to
the hypothesis that these proteins may function to protect the fetus from
attack by the maternal immune system. With the purpose of developing an animal
model to study the function of PSGs, we have studied the effects of murine
PSG17 on macrophages and we have cloned its receptor. RAW 264.7 cells and
peritoneal macrophages were treated with recombinant PSG17N, which consists
of the N-domain of PSG17. PSG17N induced production of IL-l 0 and IL-6 at
the protein and RNA levels in these cells. Secretion of TGF$1 and PGE2 was
also induced upon treatment with PSG17N. We then examined the PSG17-RAW cell
surface binding interaction. Scatchard analysis revealed that there are approximately
1770 binding sites per cell with a Kd of 2.2 X 10-11 M. For the purpose of
cloning the PSG17 receptor, we screened a RAW cell cDNA library by panning.
The receptor was identified as CD9, a member of the tetraspanin superfamily.
The specificity of the CD9-PSG17 interaction was confirmed by ELISA and flow
cytometry in CD9-transfected cells. Furthermore, binding of PSG17 to CD9-expressing
cells was blocked with anti-CD9 antibodies. We then tested whether murine
PSG18 and 19, which share with PSG17 the ability to induce cytokines in macrophages,
use CD9 as their receptor. These proteins do not bind to CD9. In conclusion,
we have identified the first receptor for a PSG as well as the first natural
ligand for a member of the tetraspanin superfamily.