Browsing by Subject "Department of Laboratory Medicine and Pathology"
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Item The Analysis of Pyridyloxobutyl RNA Adducts in Rats Treated With 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone(2009-04-08) Muzic, JohnTobacco-specific nitrosamines are potent carcinogens formed from parent compounds such as nicotine during the curing process of tobacco. The cytochrome P450 enzyme family metabolically activates these nitrosamines, which then attach pyridyloxobutyl (POB) groups to DNA bases. The formation of POB-DNA adducts in tissues of rats treated with tobacco-specific nitrosamines have been demonstrated in previous studies. These adducts can potentially lead to mutations in DNA which promote the formation of tumors. However there exists no data on the formation of POB-RNA adducts. RNA adducts could be important in carcinogenesis, and could potentially be a more reliable biomarker than DNA adducts for tobacco-specific nitrosamine exposure. The objective of our project was to chemically characterize and quantify POB-RNA adducts in the tissue of rats treated with a nitrosamine compound, specifically 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). RNA was isolated from rat liver treated with NNK over a course of 20 weeks and from untreated liver. Combined liquid chromatography-mass spectrometry and high performance liquid chromatography were used to identify RNA adducts. The results indicate the presence of POB-RNA adducts in the treated livers. Further work will involve synthesizing standards by reacting NNK with nucleosides and confirming the structure of adducts with NMR. The results of this study will confirm the presence of RNA adducts due to nitrosamine exposure and provide insight into the utility of RNA adducts as a biomarker used for chemopreventative strategies.Item Biological Function of Nectin 4 in Ovarian Cancer(2012-04-18) Meyer, AdamOvarian Cancer Overview: 5th leading cause of cancer death for women in the U.S.; Most patients diagnosed after metastasis, when survival rates are low; Early diagnosis yields 93% five year survival rate. Biomarkers and Nectin 4: Biomarkers have different properties: early detection, clues to therapy effectiveness, and possible prognostic applications; Nectin 4 has been identified by the Skubitz lab as a possible biomarker. Nectins belong to a family of immunoglobulin-like proteins important in cell to cell adhesion; A study of 500 ovarian cancer tumors showed 48.6% stained for Nectin 4 in the tumor while 53% of ovarian cancer blood samples tested positive. Nectin 4 also expressed in lung cancer. Our hypothesis is that knocking down the expression of Nectin 4 will inhibit ovarian cancer cell function and metastasis.Item IL-4 Induces Protection of Porcine Endothelial Cells from Anti-Endothelial Cell Antibody in Association with Upregulation of Claudin-5(2010-04-21) Goldish, DannyInterspecies organ transplantation offers a potential strategy to the global shortage in vital human organs for donation. Multiple obstacles remain before rejection of foreign organ grafts (xenotransplantation) can be avoided. In pig-to-primate combinations, the vascular endothelium of the transplant is the main target of injury by the host immune system. We are using an in vitro system in which pig endothelial cells (EC) are modified to make them resistant to injury by anti-EC antibodies (abs) in human blood. These abs damage the EC by causing cellular retraction and intercellular gap formation. My aim is to study methods and mechanisms that protect the EC from injury caused by the abs. The cytokine interleukin-4 (IL-4) induces protection of EC from apoptosis and from killing by human complement. My results demonstrated that pretreatment of the EC with pig IL-4 decreases the amount of abinduced cellular retraction and intercellular gap formation. This finding suggested that IL-4 might regulate the expression of proteins that maintain cell-to-cell junctions in the monolayer. Using immunofluoresce, we examined the expression of the junction proteins CD31, VEcadherin, and claudin-5, in IL-4-treated and untreated EC. We found that IL-4 strongly induces claudin-5 expression, but not expression of VE-cadherin or CD31. We now plan to use siRNA silencing of claudin-5 to investigate whether increases in claudin-5 protein are important for protection of EC from ab-induced damage. If this silencing abolishes EC protection, claudin-5 must play a pivotal role in IL-4-induced protection. Conversely, if protection still occurs, claudin-5 is an unnecessary side reaction of the protection. This information will help uncover mechanisms behind IL-4 induced protection, and contribute to new approaches for xenotransplantation.Item Interview with Christopher G. Chute(2014-12-04) Chute, Christopher G.; Tobbell, DominiqueChristopher Chute begins by discussing his educational background and his decision to move to the Mayo Clinic in the late 1980s. Next, he discusses some of the health informatics research and educational projects that the Mayo Clinic and the University of Minnesota have collaborated on. Dr. Chute describes in detail the main research projects that he and the Division of Biomedical Informatics have worked on since the late 1980s, including research in the areas of biomedical terminology and ontology and the management of patient data in electronic medical records. He discusses his role in the University of Minnesota’s National Library of Medicine Research Training Program and the eventual formal incorporation of the Mayo Clinic into the training program. He discusses the changes in the training program over the course of the 1990s and early 2000s in the context of broader changes in the field of health informatics in particular and biomedical research more generally. Dr. Chute next discusses the efforts, beginning in the mid-2000s, to establish a collaborative health informatics training program between the Mayo Clinic, Arizona State University, and the University of Minnesota. He also discusses the process by which both the Mayo Clinic and the University of Minnesota secured Clinical Translation Science Awards. Finally, Dr. Chute reflects on the interprofessionalism that has characterized health informatics at the University of Minnesota.Item Interview with David Brown(University of Minnesota, 2012-05-09) Tobbell, Dominique A.; Brown, David M.David Brown begins by describing his childhood and education in Illinois. He discusses his experience attending medical school in the 1960s and his decision to join the University of Minnesota’s Department of Pediatrics. He describes his experiences with Ellis Benson and others with whom he worked in the Department. He discusses the role of women in laboratory medicine and his work in comparative endocrinology. He explains the differences in the administrations of several different deans of the Medical School and the School’s changing relationship with the University (and later, Fairview) Hospital. He describes some of the issues of town/gown in Minneapolis and in Minnesota at large, especially related to pediatric medicine. He describes his decision to become an administrator and his own tenure as Dean of the Medical School, the development of the Masonic Cancer Center, and the University’s ALG scandal. He concludes with his retirement and his discovery of a passion for art.Item Interview with Donald Connelly(2015-04-01) Connelly, Donald; Tobbell, DominiqueDonald Connelly begins by discussing his educational background, including his early interest in biomedical computing. He describes his first years in the Department of Laboratory Medicine and Pathology including the state of computing in laboratories in the 1970s, the atmosphere of the Department, and his experiences as director of the Laboratory Data Division and acting director of the Outpatient Laboratory. Next, Dr. Connelly discusses his experiences as a Ph.D. student in the Division of Health Computer Sciences. He goes on to describe his early research developing ways to graphically display laboratory data to clinicians, and his subsequent research with Theodore Thompson, MD, to develop a clinical workstation for the University of Minnesota’s Neonatal Intensive Care Unit. He also describes his work developing an automated decision support system for blood bank personnel assessing requests for platelets. Dr. Connelly next discusses the courses he taught in the Division of Health Computer Sciences; the National Library of Medicine Training Grant programs; and the interdisciplinarity and interprofessionalism of health informatics. He reflects upon the leadership of Eugene Ackerman and Laël Gatewood, the challenges each faced due to the lack of strong institutional support for the Division of Health Computer Sciences, and the increased status of health informatics within the University following the establishment of the Clinical and Translational Science Institute. He also discusses his experiences directing the Division of Health Computer Sciences. Dr. Connelly briefly discusses the relationships between the Division of Health Computer Sciences and the Mayo Clinic, the Biomedical Library, and the Minnesota Department of Health. He next discusses work that he has done in the area of electronic health records. Dr. Connelly goes on to discuss the establishment of the Institute for Health Informatics; the directorship of Julie Jacko; and the establishment of the Master’s in Health Informatics. Finally, Dr. Connelly reflects on some of the major changes he has in health informatics observed over his career.Item Interview with Ellis Benson(University of Minnesota, 2009-12-01) Tobbell, Dominique A.; Benson, EllisEllis Benson starts with his background, including growing up in China (his parents were missionaries), why he went into medicine and academic medicine, and his educational history. He discusses his residency in pathology at the UMN, his internal medicine residency at the VA Hospital, joining the Department of Laboratory Medicine, his work while he was in charge of the blood bank, his work as director of Clinical Laboratories, and his work as head of Pathology. He offers reflections on cardiac surgeons Richard Varco and Walter Lillehei and how they dealt with the Lab and the Blood Bank, as well as working with the Department of Surgery and surgeons more generally. He discusses the appointment of Robert Howard as dean of the College of Medical Sciences in 1959 and Howard’s deanship, the Vice President of the Health Sciences search and the appointment of Lyle French. He also discusses Franz Halberg, and David Brown. He discusses his work on protein chemistry and going to the Carlsberg Laboratory in Copenhagen, the UMN’s Clinical Laboratory providing community services to anyone in Minnesota, the Medical Technology program, why technologists tended to be women, and specialization in medicine. He describes the founding of the Academy of Clinical Laboratory Physicians and Scientists, the creation of the Department of Laboratory Medicine at the UMN in 1959, space issues in the late 1950s and early 1960s, the merger of Laboratory Medicine and Pathology, and the relationships between the clinical and basic science departments within the Medical School. He discusses the attempt to establish a second medical school in St. Paul, relations between the Medical School and other UMN health science schools in the 1960s and 1970s, faculty attitudes toward the 4 reorganization in 1970, the impact of the introduction of Medicaid and Medicare, the attempt to create a School of Allied Health Sciences in the late 1960s and early 1970s, relations between the Medical School and the Mayo Clinic, and relations with the University Hospitals.Item Interview with Grace Ederer(University of Minnesota, 2012-07-30) Hagens, Emily; Ederer, Grace M.Grace Ederer begins her interview with a description of her upbringing, her education, and her decision to enter the field of medical technology. She then recalls the early stages of her career and her work at the University of Minnesota from 1952 to 1982. Ederer describes the role of women in medical technology, the building of the new medical sciences building, and Dr. Gerald T. Evans’ efforts to reorganize the clinical laboratories and medical technology to integrate them into the Medical School. Ederer also discusses her decision to adopt a dog that had been used in experiments conducted C. Walton Lillehei on hypothermia in open-heart surgery. She goes on to describe her changing positions at the University, her teaching, her research, and her pursuit of a master’s in public health. She also talks about her interactions with Dr. Evans, Dr. Ellis Benson, and Dr. Lillehei. She then discusses the Medical Technology Program, her work with Barbara Tucker on laboratory safety and ethics, her work with Ruth Hovde and Verna Rausch, the changing curriculum, dealing with the high volume of lab work, working with graduate students, her experiences with Robert Howard, and efforts to establish a school of Allied Health Sciences.Item Interview with Karen Karni(University of Minnesota, 2012-09-11) Hagens, Emily; Karni, KarenDr. Karen Karni begins her interview with an overview of her educational history and how she came to be director of the medical technology program at the University of Minnesota. She then, in more detail, discusses the following: her interest in medical technology; her time as an undergraduate student at the University; generalist and specialty work in medical technology; her work in Bar Harbor, Maine and Virginia, Minnesota; and her time at State University of New York at Buffalo. In reviewing her time at the University of Minnesota in the medical technology program, Dr. Karni covers the following topics: working with Verna Rausch; changes in the curriculum; her doctoral research and certification exams for laboratory personnel; the hierarchy within which laboratory personnel work; the culture of the Medical School and the Rajender Consent Decree; Ellis Benson’s tenure as chair of the Department of Laboratory Medicine and Pathology; Dave Brown’s tenure as chair; Leo Furcht as chair; her work with the Minnesota Society for Medical Technology; relationships among the divisions within the Department of Laboratory Medicine and Pathology; her appointment and tenure as director of the medical technology program; her work through Project Hope and the National Accrediting Agency for Clinical Laboratory Sciences; the changing demography of students within the medical technology program; and the tenures of several vice presidents of the Academic Health Center. She goes on to consider changes in medical technology more broadly, evolving requirements for tenure, simulation in medical technology education, and automation in the field. She concludes with thoughts on how the University’s medical technology program fits in the history of laboratory science.Item Interview with Lynda Ellis(University of Minnesota, 2014-10-21) Ellis, Lynda; Tobbell, DominiqueLynda Ellis begins by discussing her educational background and her arrival at the University of Minnesota. She describes her first years in the Division of Health Computer Sciences, the atmosphere of the Department of Laboratory Medicine and Pathology, and her colleagues in the Department. She then discusses her initial research in computer-based patient education; the graduate program in Biometry and Health Information Systems; and her year of leave at 3M. Dr. Ellis next describes her collaborative work with Larry Wackett and the development of the University of Minnesota Biocatalysis/Biodegradation Database, and then returns to the subject of her work on computer-based patient education. She discusses the National Library of Medicine Training Grant program; the development of the Health Sciences Instructional Computing Laboratory; the important role of the Biomedical Library in the history of health informatics at the University; the leadership styles of Eugene Ackerman and Laël Gatewood; and the number of women in health informatics.Item Interview with Martin LaVenture(2015-03-22) LaVenture, Martin; Tobbell, DominiqueMartin (Marty) LaVenture received his BS in Natural Science from St. John’s University in Collegeville, Minnesota in 1973, and a Masters in Public Health in Epidemiology in 1976 and Ph.D. in Health Informatics in 2004 from the University of Minnesota. From 1976 to 1978, Dr. LaVenture served as epidemiologist and surveillance coordinator in the Immunization Program Section of the Minnesota Department of Health. In 1978, Dr. LaVenture joined the Wisconsin Division of Health in Madison, where he held the position of assistant state epidemiologist and communicable disease coordinator until 1987. Between 1987 and 1990, he served as director of the Cohort Public Health Division of Epic Systems Corp., in Minneapolis where he worked as a developer of software systems for health information management. In 1990, Dr. LaVenture returned to the Minnesota Department of Health where he held the position of supervisor, Immunization Assessment and Registries Unit in the Division of Disease Prevention and Control. From December 1995 through December 1997, he served as manager, Acute Disease Prevention Services Section in the Division of Disease Prevention and Control. Since December 1997, Dr. LaVenture has served as Director of Health Informatics and since 2009 he has served as Director of the Office of Health Information Technology and e-Health at the Minnesota Department of Health. As part of this, he leads the statewide Minnesota e-Health Initiative, a public-private collaborative chartered in 2004 to advance health information technology adoption and use in Minnesota. In 1992, Dr. LaVenture joined the graduate program in Health Informatics at the University of Minnesota, receiving his Ph.D. in 2004. Since 2004, he has served as a core member of faculty at the University of Minnesota in Health Informatics. In 2011, Dr. LaVenture was elected as a fellow of the American College of Medical Informatics.Item Interview with Milton Corn(2014-11-21) Corn, Milton; Tobbell, DominiqueMilton Corn begins the interview discussing the definition of health informatics and the early National Library of Medicine Research Training in Medical Informatics programs, including the University of Minnesota’s training program. Dr. Corn describes his first introduction to medical informatics while serving as dean of Georgetown University School of Medicine and his decision to join the NLM in 1990. He describes at length the evolution of the NLM Research Training Program and the related history of the University of Minnesota’s training program based on the evaluations the NLM performed of the training program every five years. He discusses the University of Minnesota and Mayo Clinic’s efforts to establish a collaborative training program with Arizona State University. He also discusses the implications of Minnesota’s decision not to fully pursue bioinformatics when the NLM shifted the focus of its training program in the 1990s. Dr. Corn goes on to discuss the development of the Clinical and Translational Science Awards and the influence of the awards on health informatics research.Item Interview with Robert McCollister(University of Minnesota, 2009-12-09) Tobbell, Dominique A.; McCollister, RobertRobert McCollister begins by discussing his background, including his education and medical training. He discusses getting into administration, how he became involved with the curriculum, working in the Department of Laboratory Medicine, and his work as assistant dean of student affairs. He offers many reflections on the development of the Medical School curriculum. He describes the work to improve the governance in the Medical School in the mid-1960s, revising the curriculum in the 1960s, the expansion of Medical School class size in the 1960s, recruitment of minority students, and Robert Howard’s departure as dean of the College of Medical Sciences and the appointment of Lyle French as the first Vice President of the Health Sciences. He discusses the Educational Policy Committee, the large number of women in leadership positions in the Department of Laboratory Medicine, the reorganization of the health sciences in 1970, department “fiefdoms”, Curriculum 2010, the Comprehensive Clinic, the Department of Family and Community Health, specialization in medicine, Phase C of the medical school curriculum, the teaching of behavioral science within the curriculum, transfer students from the Dakotas, the Program in Human Sexuality, and the student attempt to get a medical ethics course included in the curriculum. He talks about Ray Amberg, C.J. Watson, Richard Ebert, Frederic Kottke, Robert Howard, Benjamin Fuller, Frank Cerra, and Lyle French.Item Interview with Stanley Finkelstein(University of Minnesota, 2014-11-06) Finkelstein, Stanley; Tobbell, DominiqueStanley Finkelstein begins by discussing his educational background and his arrival at the University of Minnesota. He describes at length his research in the field of home monitoring and telehealth, including his research with Jay N. Cohn on the development of a device to measure and monitor arteriovascular compliance in order to diagnose and monitor hypertension and congestive heart failure; his research with Warren Warwick and the development of the first home monitoring system for cystic fibrosis patients; and the subsequent development of home monitoring of lung transplant patients in collaboration with Marshall Hertz. Dr. Finkelstein goes on to discuss the NLM training grant program; the lack of institutional support provided to the Division of Health Computer Sciences; the development of the Institute for Health Informatics; the leadership of Eugene Ackerman and Laël Gatewood; the number of women in the field of biomedical engineering and health informatics; the relationship between the Division of Health Computer Sciences and the Biomedical Library; the collaborative relationship between the University of Minnesota and the Mayo Clinic; and the development of the Masters in Health Informatics.Item Interview with Stuart Speedie(2015-01-29) Speedie, Stuart; Tobbell, DominiqueStuart Speedie begins by discussing his educational background and his early career spent first at the Northwest Regional Educational Laboratory in Portland, Oregon, and then at the University of Maryland School of Pharmacy where he served as Director of Education. He discusses his early interest in information systems and technology and his five-year NSF-funded research project on the development of expert systems on the appropriate use of drugs in hospital settings, which he developed during a sabbatical year at Stanford University. He describes his responsibilities disseminating information technology at the University of Maryland and the information systems research he conducted there. Next he discusses his move to the University of Minnesota, his appointment in the Division of Health Computer Sciences and in the office of the Provost of the Academic Health Center, and his role on the Provost’s Reengineering Task Force on Information Technology. He discusses his role within the Division of Health Computer Sciences (subsequently renamed the Division of Health Informatics); his work in telehealth and telemedicine; and his collaboration with Stanley Finkelstein on the use of telehealth technologies in homecare. He next discusses the NLM Research Training in Medical Informatics program. He describes the efforts to establish the terminal Masters in Health Informatics; the influence of different directors—Laël Gatewood, Donald Connelly, Julie Jacko—on the Division and later, the Institute for Health Informatics; his collaborations with Donald Connelly on the impact of health information exchange on patients and hospital emergency departments; the influence of Connie Delaney’s appointment to the Institute for Health Informatics; and the Division and Institute’s long-term relationship with the Mayo Clinic.Item Mechanisms of Androgen-Mediated Repression of the Maspin Tumor Suppressor Gene in Prostate Cancer(2009-04-08) Bader, DavidIt is estimated that one in six men in North America will be diagnosed with prostate cancer (PCa) during his lifetime. Localized PCa is often treated using surgery and radiation. Advanced and metastatic PCa can be treated by blocking the production or action of androgens, the male sex hormones. This androgen depletion therapy is only temporarily successful because PCa frequently returns in an androgen-refractory form that is resistant to hormonal manipulations and capable of growing in an androgen-depleted environment. Androgen receptor (AR) is a nuclear receptor transcription factor necessary for normal prostate cell growth and function as well as for growth of PCa. Androgens activate the AR, which translocates to the nucleus where it transcriptionally activates or represses target genes. One such gene is the Maspin tumor suppressor. Maspin is a proteinase inhibitor that serves to prevent proteinase degradation of the extracellular matrix, which is prerequisite to tumor invasion and metastasis. Androgens transcriptionally repress Maspin, but the mechanisms have not yet been fully characterized. To investigate the mechanisms of Maspin repression, a plasmid containing the luciferase reporter gene under the control of the Maspin promoter was constructed and transfected into VCaP and LNCaP PCa cell lines. Transfected cells were treated with dihydrotestosterone (a natural androgen) or mibolerone (a synthetic androgen) for 24 hours. Luciferase activity was subsequently measured by dual luciferase assay. These experiments have indicated that the AR may not directly repress Maspin transcription. Ongoing research will utilize real time PCR to determine whether AR inhibits Maspin transcription via a direct or indirect mechanism.Item Optimizing Humoral Immunity to a Soluble Subunit gp350 Epstein-Barr Virus Vaccine(2022) Meirhaeghe, MadelineItem Synthesis of Novel PMMA Monomers with Carbohydrate Functionality(2009-04-08) Otto, Rita M.Polymethylmethacrylate (PMMA) is a mostly biologically inert material that has many applications as a biomaterial . The ability to functionalize PMMA with carbohydrates easily and at a low cost is of great interest because of their possible commercial applications. It has been shown previously that synthesis of PMMA monomers with carbohydrate functionalities is possible, but most procedures are costly and time consuming. Here is shown a facile and inexpensive procedure for the synthesis of two PMMA monomers with carbohydrate functionalities.