Object Relations and Identity Disturbances in Bulimic Women

Problem. Although diagnostic criteria of bulimia center on weight- and food-related issues, eating disorders may be viewed as a response to deficits in self-regulatory functions. The purpose of this study was to investigate the relationship between the severity of bulimia, object relations, and identity. This study tested the hypotheses that women with a more severe eating pathology have high scores on object-relations disturbance as well as identity disturbance. It was postulated that women who have been assessed as having a more cohesive ego might respond to cognitive behavioral therapy while those who are assessed as having less intact ego resources may require more intensive psychodynamic approaches. Method. The study involved the administration of three tests by therapists who were treating women diagnosed with bulimia nervosa according to DSM-IV criteria. The test instruments included the following: Bulimia Test-Revised, Bell Object Relations Inventory, and the Erwin Identity Scale. An interview was conducted on a selected group of 12 subjects. Results. There were statistically significant correlations between the severity of bulimia and the severity of object relations and identity disturbance. Specifically, the Alienation subscale of the Bell Object Relations Inventory and the Confidence subscale of the Erwin Identity Scale had the strongest correlation with the BULIT-R. The qualitative results indicated that a number of themes were strongly identified by both High Bulimics and Low Bulimics. Conclusions. The quantitative analysis indicated there was a relationship between the severity of object relations, identity disturbance, and bulimia. However, the qualitative analysis identified many of the women, in the Low Bulimic group, had significant disturbances in their relationships as well as their opinion of their body. It was concluded that both groups exhibited significant object relations and identity disturbances. Therefore, it is suggested that a more psychodynamic approach is useful for understanding the adaptive functions of bulimia

The Deconvolution Analysis of the Radiohippurate Renogram

The evaluation of kidney function is a necessary procedure in assessing the extent of renal disease in today\u27s population. In particular, this assessment should include measurements of the patient\u27s plasma flow into and urine flow from each kidney. Changes in either measurement from accepted normal ranges indicate the presence of a disease process. The combination of radioactive tracer methods with data analysis using models describing biological kinetics has demonstrated the potential of large computers in the assessment of renal function. However, the requirement for sophiticated computer resources has limited the widespread application these techniques might otherwise receive. This work investigates the application of minicomputers for performing this data analysis using digital filtering (deconvolution) methods. A multiparameter compartmental model describing the distribution of 131I-orthoiodohippurate in the renal-vascular system is presented. Differential equations are developed which, when solved, describe the time behavior of this tracer material following its intravenous injection into the body. Analysis of this modeled system shows that only a few parameter values need be identified to characterize the functional vistate of thP renal system in terms of plasma flow and urine flow. The values for these parameter values can be obtained from the renal impulse responses, if these responses are available. Since the renogram can be modeled by a convolution of the renal impulse response with an appropriate renal input function, it follows that isolation of the renal impulse response can be accomplished by deconvolution. The development of this digital filter for performing these deconvolutions is developed in detail. Following the deconvolution of the renogram, the resulting sequence can be analyzed and values assigned to the parameters requiring estimation. These parameter values, in turn, are used to provide measures of plasma flow to and urine flow from each kidney. Computer simulation demonstrated the proper behavior of the deconvolution filter. Clinical application demonstrated the ability to estimate unilateral plasma flow but urine flow could not be computed confidently. In conclusion, it is felt the model does represent an adequate description of hippurate kinetics but does warrant further investigation. Although deconvolution techniques present an economical and efficient means for renal data analysis, the clinical utility cannot be fully realized until the signal-to-noise ratio of the data is improved

Effects of zebra mussel attachment on the foraging behaviour of a larval dragonfly, Macromia illinoiensis

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/88127/1/j.1365-2311.2011.01329.x.pd

Development of novel adenoviral vectors to overcome challenges observed with HAdV-5 based constructs

Recombinant vectors based on human adenovirus serotype 5 (HAdV-5) have been extensively studied in pre-clinical models and clinical trials over the last two decades. However, the thorough understanding of the HAdV-5 interaction with human subjects has uncovered major concerns about its product applicability. High vector-associated toxicity and widespread pre-existing immunity have been shown to significantly impede the effectiveness of HAdV-5 mediated gene transfer. It is therefore that the in depth knowledge attained working on HAdV-5 is currently being used to develop alternative vectors. Here, we provide a comprehensive overview of data obtained in recent years disqualifying the HAdV-5 vector for systemic gene delivery as well as novel strategies being pursued to overcome the limitations observed with particular emphasis on the ongoing vectorization efforts to obtain vectors based on alternative serotypes

Key Role of the Scavenger Receptor MARCO in Mediating Adenovirus Infection and Subsequent Innate Responses of Macrophages

ABSTRACT The scavenger receptor MARCO is expressed in several subsets of naive tissue-resident macrophages and has been shown to participate in the recognition of various bacterial pathogens. However, the role of MARCO in antiviral defense is largely unexplored. Here, we investigated whether MARCO might be involved in the innate sensing of infection with adenovirus and recombinant adenoviral vectors by macrophages, which elicit vigorous immune responses in vivo. Using cells derived from mice, we show that adenovirus infection is significantly more efficient in MARCO-positive alveolar macrophages (AMs) and in AM-like primary macrophage lines (Max Planck Institute cells) than in MARCO-negative bone marrow-derived macrophages. Using antibodies blocking ligand binding to MARCO, as well as gene-deficient and MARCO-transfected cells, we show that MARCO mediates the rapid adenovirus transduction of macrophages. By enhancing adenovirus infection, MARCO contributes to efficient innate virus recognition through the cytoplasmic DNA sensor cGAS. This leads to strong proinflammatory responses, including the production of interleukin-6 (IL-6), alpha/beta interferon, and mature IL-1α. These findings contribute to the understanding of viral pathogenesis in macrophages and may open new possibilities for the development of tools to influence the outcome of infection with adenovirus or adenovirus vectors. IMPORTANCE Macrophages play crucial roles in inflammation and defense against infection. Several macrophage subtypes have been identified with differing abilities to respond to infection with both natural adenoviruses and recombinant adenoviral vectors. Adenoviruses are important respiratory pathogens that elicit vigorous innate responses in vitro and in vivo. The cell surface receptors mediating macrophage type-specific adenovirus sensing are largely unknown. The scavenger receptor MARCO is expressed on some subsets of naive tissue-resident macrophages, including lung alveolar macrophages. Its role in antiviral macrophage responses is largely unexplored. Here, we studied whether the differential expression of MARCO might contribute to the various susceptibilities of macrophage subtypes to adenovirus. We demonstrate that MARCO significantly enhances adenovirus infection and innate responses in macrophages. These results help to understand adenoviral pathogenesis and may open new possibilities to influence the outcome of infection with adenoviruses or adenovirus vectors. IMPORTANCE Macrophages play crucial roles in inflammation and defense against infection. Several macrophage subtypes have been identified with differing abilities to respond to infection with both natural adenoviruses and recombinant adenoviral vectors. Adenoviruses are important respiratory pathogens that elicit vigorous innate responses in vitro and in vivo. The cell surface receptors mediating macrophage type-specific adenovirus sensing are largely unknown. The scavenger receptor MARCO is expressed on some subsets of naive tissue-resident macrophages, including lung alveolar macrophages. Its role in antiviral macrophage responses is largely unexplored. Here, we studied whether the differential expression of MARCO might contribute to the various susceptibilities of macrophage subtypes to adenovirus. We demonstrate that MARCO significantly enhances adenovirus infection and innate responses in macrophages. These results help to understand adenoviral pathogenesis and may open new possibilities to influence the outcome of infection with adenoviruses or adenovirus vectors.</jats:p

Carbon Neutral luxury Dog House

ME450 Capstone Design and Manufacturing Experience: Winter 2021Our goal for this project was to design an outdoor shelter for a large dog which will be carbon neutral in use and in construction. This design was made for a specific household of stakeholders, including their growing golden retriever. This shelter maintains a comfortable temperature for the dog under all Michigan seasonal outdoor temperatures. The shelter is designed to reduce bugs and to optimize accessibility for maintenance and cleaning. Various design decisions were made for the specific end users, such as opening windows for internal airflow and visibility to the outdoors. This design is made to be easy and affordable to construct, while also leaving a carbon neutral effect on the environment.Dr. Steven Skerlos: UM Mechanical Engineeringhttp://deepblue.lib.umich.edu/bitstream/2027.42/167639/1/Team_22-Carbon_Neutral_Luxury_Dog_House.pd

Vaccine Platforms Combining Circumsporozoite Protein and Potent Immune Modulators, rEA or EAT-2, Paradoxically Result in Opposing Immune Responses

Malaria greatly impacts the health and wellbeing of over half of the world's population. Promising malaria vaccine candidates have attempted to induce adaptive immune responses to Circumsporozoite (CS) protein. Despite the inclusion of potent adjuvants, these vaccines have limited protective efficacy. Conventional recombinant adenovirus (rAd) based vaccines expressing CS protein can induce CS protein specific immune responses, but these are essentially equivalent to those generated after use of the CS protein subunit based vaccines. In this study we combined the use of rAds expressing CS protein along with rAds expressing novel innate immune response modulating proteins in an attempt to significantly improve the induction of CS protein specific cell mediated immune (CMI) responses.BALB/cJ mice were co-vaccinated with a rAd vectors expressing CS protein simultaneous with a rAd expressing either TLR agonist (rEA) or SLAM receptors adaptor protein (EAT-2). Paradoxically, expression of the TLR agonist uncovered a potent immunosuppressive activity inherent to the combined expression of the CS protein and rEA. Fortunately, use of the rAd vaccine expressing EAT-2 circumvented CS protein's suppressive activity, and generated a fivefold increase in the number of CS protein responsive, IFNγ secreting splenocytes, as well as increased the breadth of T cells responsive to peptides present in the CS protein. These improvements were positively correlated with the induction of a fourfold improvement in CS protein specific CTL functional activity in vivo.Our results emphasize the need for caution when incorporating CS protein into malaria vaccine platforms expressing or containing other immunostimulatory compounds, as the immunological outcomes may be unanticipated and/or counter-productive. However, expressing the SLAM receptors derived signaling adaptor EAT-2 at the same time of vaccination with CS protein can overcome these concerns, as well as significantly improve the induction of malaria antigen specific adaptive immune responses in vivo

A New Adenovirus Based Vaccine Vector Expressing an Eimeria tenella Derived TLR Agonist Improves Cellular Immune Responses to an Antigenic Target

Adenoviral based vectors remain promising vaccine platforms for use against numerous pathogens, including HIV. Recent vaccine trials utilizing Adenovirus based vaccines expressing HIV antigens confirmed induction of cellular immune responses, but these responses failed to prevent HIV infections in vaccinees. This illustrates the need to develop vaccine formulations capable of generating more potent T-cell responses to HIV antigens, such as HIV-Gag, since robust immune responses to this antigen correlate with improved outcomes in long-term non-progressor HIV infected individuals.. Moreover, we show that these improved responses were dependent upon improved TLR pathway interactions.The data presented in this study illustrate the potential utility of Ad-based vectors expressing TLR agonists to improve clinical outcomes dependent upon induction of robust, antigen specific immune responses

Essential Role of Cdc42 in Ras-Induced Transformation Revealed by Gene Targeting

The ras proto-oncogene is one of the most frequently mutated genes in human cancer. However, given the prevalence of activating mutations in Ras and its association with aggressive forms of cancer, attempts to therapeutically target aberrant Ras signaling have been largely disappointing. This lack of progress highlights the deficiency in our understanding of cellular pathways required for Ras-mediated tumorigenesis and suggests the importance of identifying new molecular pathways associated with Ras-driven malignancies. Cdc42 is a Ras-related small GTPase that is known to play roles in oncogenic processes such as cell growth, survival, invasion, and migration. A pan-dominant negative mutant overexpression approach to suppress Cdc42 and related pathways has previously shown a requirement for Cdc42 in Ras-induced anchorage-independent cell growth, however the lack of specificity of such approaches make it difficult to determine if effects are directly related to changes in Cdc42 activity or other Rho family members. Therefore, in order to directly and unambiguously address the role of Cdc42 in Ras-mediated transformation, tumor formation and maintenance, we have developed a model of conditional cdc42 gene in Ras-transformed cells. Loss of Cdc42 drastically alters the cell morphology and inhibits proliferation, cell cycle progression and tumorigenicity of Ras-transformed cells, while non-transformed cells or c-Myc transformed cells are largely unaffected. The loss of Cdc42 in Ras-transformed cells results in reduced Akt signaling, restoration of which could partially rescues the proliferation defects associated with Cdc42 loss. Moreover, disruption of Cdc42 function in established tumors inhibited continued tumor growth. These studies implicate Cdc42 in Ras-driven tumor growth and suggest that targeting Cdc42 is beneficial in Ras-mediated malignancies

A Non Membrane-Targeted Human Soluble CD59 Attenuates Choroidal Neovascularization in a Model of Age Related Macular Degeneration

Age related macular degeneration (AMD) is the most common cause of blindness amongst the elderly. Approximately 10% of AMD patients suffer from an advanced form of AMD characterized by choroidal neovascularization (CNV). Recent evidence implicates a significant role for complement in the pathogenesis of AMD. Activation of complement terminates in the incorporation of the membrane attack complex (MAC) in biological membranes and subsequent cell lysis. Elevated levels of MAC have been documented on choroidal blood vessels and retinal pigment epithelium (RPE) of AMD patients. CD59 is a naturally occurring membrane bound inhibitor of MAC formation. Previously we have shown that membrane bound human CD59 delivered to the RPE cells of mice via an adenovirus vector can protect those cells from human complement mediated lysis ex vivo. However, application of those observations to choroidal blood vessels are limited because protection from MAC- mediated lysis was restricted only to the cells originally transduced by the vector. Here we demonstrate that subretinal delivery of an adenovirus vector expressing a transgene for a soluble non-membrane binding form of human CD59 can attenuate the formation of laser-induced choroidal neovascularization and murine MAC formation in mice even when the region of vector delivery is distal to the site of laser induced CNV. Furthermore, this same recombinant transgene delivered to the intravitreal space of mice by an adeno-associated virus vector (AAV) can also attenuate laser-induced CNV. To our knowledge, this is the first demonstration of a non-membrane targeting CD59 having biological potency in any animal model of disease in vivo. We propose that the above approaches warrant further exploration as potential approaches for alleviating complement mediated damage to ocular tissues in AMD