Browsing by Subject "Department of Medicine"

Now showing 1 - 17 of 17

Clinical Risk Factors for Infection and Antibiotic Resistance in BMT Patients
(2012-04-18) Bock, Allison
Bacterial infections continue to be a leading cause of mortality and morbidity in blood or bone marrow transplant (BMT) patients. The relative importance of different clinical features (donor type, graft cell source, and conditioning regimen) on the incidence and timing of post-transplant bacterial infections is uncertain, but a detailed analysis could better guide prevention and therapy. We retrospectively analyzed the incidence and risk factors for bacterial infection, as well as patterns of antibiotic resistance, in 834 BMT patients at the University of Minnesota from 2005-2010. We found that donor type has the greatest impact on the incidence of infection in BMT patients out to 100 days post-transplant. Full intensity, myeloablative conditioning, compared to reduced intensity conditioning is also associated with a greater risk of bacteremia, as is later development of acute GVHD. Additionally, BMT patients, compared to the contemporaneous hospital population, develop infections with resistance to many antibiotics used for both prophylaxis and treatment against commonly isolated bacterial organisms. These findings have important clinical implications regarding the use and selection of both prophylaxis and empiric antibiotic regimens.
Elucidating Genes that Promote the Development of Stem-Like Cells in Triple Negative Breast Cancers
(2022) Makovec, Allison; Tape, Sydney; Richter, Camden; Rennhack, Jonathan P.; Hwang, Justin
ER71 Transcriptionally Activates Brachyury: Study of Molecular Mechanisms Involved in Gene Regulation
(2010-04-21) Eck, Leslie
Congenital cardiac malformation is the most frequent birth defect which contributes to advanced heart failure in the pediatric and adult population. An enhanced understanding of the transcriptional networks that direct cardiac progenitors during heart development will have important therapeutic applications for the treatment of congenital heart disease. Furthermore, a number of parallel transcriptional pathways or networks have been proposed for the generation and regeneration of tissues such as the heart. For these reasons we predict that the definition of the transcriptional regulatory mechanisms of cardiac progenitor cells in the developing heart will enhance our understanding of cardiogenesis, congenital heart disease and myocardial regeneration. Previously, using transcriptome and RT-PCR analysis we found that ER71 was dysregulated in Nkx2-5 null embryos at both E8.0 and E9.5 in comparison to their WT littermates. This data established that ER71 is a direct downstream target of the homoedomain protein Nkx2-5. Here, we will focus on transcriptional regulation of cardiogenesis by Nkx 2.5, Etsrp71, and Brachyury (T protein).
Evaluating Primary Myelodysplastic Syndrome in Acute Myeloid Leukemia Patients
(2012-04-18) Hoff, Gretchen
The prognostic outcome of acute myelogenous leukemia (AML) patients with a history of myelodysplastic syndrome is significantly worse than those without prior MDS. It is thought that approximately 40% of AML multilineage dysplasia (MLD) patients have a history of MDS. In this study a pool of AML-MLD patients were retrospectively investigated for primary MDS.
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.
Interview with Frank Cerra
(University of Minnesota, 2014-07-31) Cerra, Frank B.; Tobbell, Dominique
Dr. Frank Cerra begins part one of his interview by describing his undergraduate education at SUNY Binghamton, his medical education at Northwestern University Medical School, and his residency at SUNY Buffalo. He then describes his recruitment to the University of Minnesota, his early goals, and his growing administrative roles. He describes the leadership implications of investigations into Antilymphocyte Globulin (ALG) on the Medical School and the merging of University Hospital with Fairview Health Services. He then discusses the following topics: his interest in surgery; the culture of the University of Minnesota’s Department of Surgery; his work with the pharmaceutical industry and the College of Pharmacy; his work developing a critical care program at the University; and his relationships with the hospital directors, hospital nursing, and the School of Nursing. In part of two his interview, Dr. Cerra intersperses reflections on finances and relations among different levels of administration in the University, the AHC, and University Hospital. He also discusses the following topics: his relationship with Neal Gault; strategic and long-range planning; the goals of the AHC; the formation of University of Minnesota Physicians; the establishment of the Biomedical Ethics Center (later the Center for Bioethics) and the Masonic Cancer Center; the investigations into ALG and Dr. John Najarian; the establishment of the Center for Drug Design; William Brody as Provost of the AHC and issues surrounding faculty tenure; and the establishment of the Institute for Health Informatics. In part three of his interview, Dr. Cerra expands on the decision to merge University Hospital with Fairview Health Services, particularly focusing on logistics, culture, and reception. He also discusses failed attempts to create a unified children’s hospital in the Twin Cities. He then reflects on the following topics: the major challenges and achievements of his tenure as senior vice president; the merging of the positions of Senior Vice President of Health Sciences and Dean of the Medical School; the creation of the Clinical and Translational Science Institute and the Biomedical Discovery District; and the medical device industry in Minnesota. He concludes by describing the University of Minnesota and Mayo Clinic partnership in research.
Interview with Henry Buchwald
(University of Minnesota, 2012-09-28) Klaffke, Lauren E.; Buchwald, Henry
Dr. Henry Buchwald begins his interview talking about his early life: fleeing Austria in the midst of the Holocaust, growing up in New York, and his baccalaureate and medical education at Columbia. He discusses how he arrived at an interest in medicine, his time in the Air Force, and his reasons for choosing to pursue a residency at the University of Minnesota. As part of his time at Minnesota, Dr. Buchwald compares the University’s research program with those of other medical schools, relates the profound influence of Owen Wangensteen on the Surgery Department, and discusses his early lab work and his studies of biochemistry, particularly lipids, with Ivan Frantz. In reviewing his changing research interests, Dr. Buchwald cites major diseases afflicting society at various times during his career: the increasing association of cholesterol with heart disease prompted his early interest in lipid uptake and spurred his work on the Program on Surgical Control of Hyperlipidemias (POSCH); the need for treatments for diabetes prompted his research into Infusaid, the first implantable infusion pump, a collaborative effort that led to the development of several other devices and eventually the establishment of a bioengineering program at the University; and finally, the ongoing obesity epidemic spurred Dr. Buchwald’s current research into the jejunoileal bypass for the treatment of obesity. In his reflections on obesity research, Dr. Buchwald discusses the high level of stigmatism associated with the disease and the difficulty of funding research into its treatment.
Interview with Ivan Frantz, Jr.
(University of Minnesota, 1995-05-05) Frantz, Ivan; Chambers, Clarke A.
Clarke A. Chambers interviews Ivan Frantz Jr., research professor in the Medical School.
Interview with John S. Najarian
(University of Minnesota, 2011-09-27) Tobbell, Dominique A.; Najarian, John S.
Dr. John Najarian begins part one of his interview with a reflection on where he was born and raised and how he became interested in medicine. He then discusses his time in the U.S. Air Force, his interest in transplantation, the research he conducted under the mentorship of Frank Dixon and Joe Feldman, his decision to return to surgical work, his time at UCSF, and his move to the University of Minnesota. Dr. Najarian then reviews his time at the University of Minnesota, covering all of the following topics: his efforts to increase the number of surgical patients and work with surgeons in the community; relations with administrators at University Hospital; the continued training of academic surgeons; relations between different departments within the Medical School; cultural differences across the United States; the organ transplantation program at the University; ethical issues in transplantation; Robert Good’s work on bone marrow transplantation; transsexual surgery at the University; the faculty practice plan and income in the Medical School; the impact of Medicare and Medicaid; the health manpower shortage and problems with manpower distribution; and efforts to recruit minority and female surgeons. Dr. Najarian begins part two of his interview by reviewing collaborations with different schools and departments across the University and the differences between the University of Minnesota and the University of California-San Francisco. He comments on his experiences as the College of Medical Sciences reorganized as the Academic Health Center and relations with the state legislature. Dr. Najarian then discusses the following topics: changes to the hospital’s Board of Governors; space and staffing issues; the expansion of the hospital in the late 1970s and 1980s; and the sale of University Hospital to Fairview. Dr. Najarian spends a considerable portion of the interview reflecting on the development of Minnesota antilymphocyte globulin (ALG) and the legal problems he faced with the FDA and the University surrounding its sale. In the remainder of the interview, Dr. Najarian discusses the following topics: the leadership of Lyle French and Neal Vanselow; the impact of the National Organ Transplant Act of 1984; transplants conducted in pediatric patients and Jamie Fisk’s successful liver transplant at eleven months old; and changes in surgical technologies. He concludes his interview with reflections on the legacy of Dr. Owen Wangensteen and other figures important to the history of the AHC.
Interview with Karen Karni
(University of Minnesota, 2012-09-11) Hagens, Emily; Karni, Karen
Dr. 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.
Interview with Vernon Weckwerth
(University of Minnesota, 2010-12-14) Tobbell, Dominique A.; Weckwerth, Vernon
Vernon Weckwerth begins his interview by discussing his upbringing during the Great Depression near the Red River Valley of Minnesota, his early education, and the rather circuitous route he took to the University of Minnesota. He discusses his graduate education, his return to Minnesota, and his professorship in health care administration in the School of Public Health. Weckwerth highlights some of his work in hospital administration within the context of the University’s land-grant mission and the creation of the Independent Study Program (ISP) to serve rural populations. As he relates his creation of ISP, Weckwerth elaborates on his educational philosophy and town/gown issues. Though his degrees were not in public health, Weckwerth took all of the public health courses offered by the University. He relates his interest in public health in terms of his rural upbringing and how he entered the field professionally. He then discusses the leadership of Gaylord Anderson, Lee Stauffer, and Edith Leyasmeyer in the School of Public Health. He also covers the following: his interpretation of dean appointments, his philosophy of public health as a field, the relationship of the School of Public Health to other departments, biostatistics, his role in the national heart study, the creation of the family practice program, the reorganization of the AHC, his experiences with the state legislature and community and professional organizations, his role in creating a doctoral program in nursing, the spread and closing of ISP, and his time on the faculty senate.
Investigating Methylglyoxal Mediated DNA Damage in Pulmonary Arterial Hypertension
(2021-08-29) Park, Anna K.; Prins, Kurt W.
Pulmonary arterial hypertension (PAH) is a progressive disorder characterized by an increase in blood pressure in the pulmonary arteries. The hypertensive force driving PAH often results in detrimental physiological changes of the pulmonary arteries and right ventricle (RV). This RV remodeling ultimately leads to RV failure and death. As a quickly progressing disease, median survival in PAH is only 5-7 years, with the strongest predictor of mortality being RV dysfunction (RVD). A key indicator of PAH in patients is mitochondrial dysfunction, and the resulting presence of methylglyoxal (MG): a toxic intermediate byproduct of glycolysis. While little is understood of the process, MG intermediates are thought to be able to induce post-translational DNA damage. The effect of MG exposure to differentiating cardiomyoblasts was tested using western blot analysis and immunohistochemistry. The DNA damage was measured using the presence of pH2AX antibodies as a marker for double-stranded DNA breaks. The results of the western blot analyses revealed that cardiomyoblasts exposed to 625µM MG for 4 hours experienced a 9.99 fold increase in pH2AX expression relative to the control (p-value < 0.05). The immunohistochemistry was conducted using both pH2AX and H2AX as markers of DNA damage, and the immunohistochemistry results revealed a positive relationship between MG exposure and DNA damage in cardiomyoblasts. Further research will be necessary in order to more fully delineate the relationship between MG and DNA damage in regards to PAH.
Protection Against Acute Kidney Injury by TUDCA
(2009-04-08) Ononenyi, Chimezie U.
Presently there is no therapy for acute kidney injury (AKI). Potentially one can protect kidneys against injury by preventing cell death following AKI. There are two types of cell death that occurs following AKI: necrosis and apoptosis. Necrosis is uncontrolled and synchronous cell death that occurs at the time of AKI. In contrast, apoptosis, or programmed cell death is an asynchronous cell death that continues to occur for days following AKI, thereby providing a window of opportunity for intervention. Tauroursodeoxycholic acid (TUDCA), a bile acid synthesized in the liver, has been shown to be effective by inhibiting apoptosis in rat models of stroke and Huntington’s disease. We hypothesized that TUDCA will be similarly effective in protection against AKI. Accordingly, the goal of this study was to investigate the protective effects of TUDCA in a rat model of ischemic AKI. We induced AKI by bilateral renal artery clamping for 45 minutes. Three rats were given 400mg/kg/day of TUDCA intraperitoneally from day -1 to day 6, while the control animals received the vehicle. We determined kidney functions by measuring blood urea nitrogen (BUN), proliferation by immunohistochemistry for Ki67, and apoptosis by TUNEL assay. Compared to a control, animals that received TUDCA had less severe kidney injury and apoptosis. In conclusion, TUDCA provides protection against acute kidney injury likely by preventing apoptosis.
SB-Transposition: MAR & SV40 Excision Assay
(2009-04-08) Goh, Diane
Sleeping Beauty transposon (SB-Tn) is an effective system that incorporates genes into vertebrate (human) chromosomes without using viruses. The Excision Assay is part of a project that determines the transposition efficiency using vector backbone elements hypothesized to increase the probability of successful gene insertion. The DNA elements used are the matrix-attachment regions (MAR) and SV40 enhancer. MAR contributes to retention of the plasmid in the host nucleus by interacting with the host nuclear proteins; SV40 enhancer promotes a high translocation rate of the SB-Tn vector into the host nucleus. The vector backbone also expresses the obligate SB transposase that must be supplied in mammalian cells to cut and paste the SB-Tn from the plasmid vector into the host chromosome. Following transfection of the vector series into a human hepatocellular carcinoma cell line (huh7), the total DNA is isolated to determine the ratio of excision product plasmids (resealed vector backbone following the cutting and pasting of the SB-Tn into the host genome to the original SB-Tn vectors transfected). This approach addresses if vector backbone modifications influence persistence of the original vector and/or excision product. If the excision plasmid, containing the SB transposase is retained in the nucleus of the host cell, the continued expression might potentially lead to harmful transposition activity remobilizing the SB-Tn integrated in the host genome.
The Search for Novel Cancer Therapies : Catalytic Inhibition of Topoisomerase II by Substituted 9-aminoacridine Derivatives
(2011-04-13) Etchison, Ryan; Jacobson, Blake; Dixon, Joe-Jay; Kratzke, Robert
The objective of this research is to test the antiproliferative effects of four novel substituted 9-aminoacridine derivatives on lung cancer and to determine their viability as potential therapeutic agents for use in a clinical setting.
ShRNA Knockdown of ID genes in Human Embryonic Stem Cells as a Possible Path Towards B and T Cell Development
(2009-04-08) Taylor, Russ
Human Embryonic Stem Cells (hESCs) are pluripotent, self-renewing cells capable of becoming any cell in the human body. Previously, our lab has derived multiple cell types from hESCs, with a particular interest in hematopoietic (blood cell) development. We have been able to successfully derive natural killer (NK) cells, a type of lymphocyte with potent anti-tumor activity. However, to date we have been unable to derive other lymphocytes (T and B cells) from hESCs. Using Umbilical Cord Blood (UCB) as a comparison for early hematopoietic development, we deduced that one possible factor for this difference could be a relatively high expression of the Inhibitor of Differentiation (IDs) transcription factors in hESCs compared to UCB. ID proteins bind to and negatively regulate basic Helix-Loop-Helix (bHLH) proteins responsible for many differentiation programs within the cell. In particular, ID2 and ID3 are known to promote NK cell development and inhibit B and T cell development. My project has been to introduce shRNA constructs into hESCs to inhibit expression of ID2 and ID3 as a means to better promote T and B cell development from hESCs. Two shRNA systems have been designed. The first uses a lentiviral vector in which the shRNA construct is constitutively expressed. The second uses a lentiviral vector containing a CRE-conditional shRNA expression system. We have introduced both of these vectors into Ntera2 embryonal carcinoma cells and hESCs. For the constitutive shRNAs, we demonstrate partial knockdown of ID2 and ID3 via qRTPCR. These constitutive knockdown ID hESCs become more difficult to culture in an undifferentiated state, and over time may have lost some of their potency. This potential problem with constitutive knockdown cells highlights the need for the inducible system, which is in progress. We anticipate that the ability to inhibit ID2/3 expression at specific timepoints of hESCs differentiation into hematopoietic cells could solve this problem and facilitate development of B and T cells from hESCs.
Spin Embryoid Bodies as an Improved Method of Blood Cell Differentiation in Human Embryonic Stem Cells and Induced Pluripotent Stem Cells
(2010-04-21) Armstrong, Rebecca
Two types of cells have been characterized as pluripotent stem cells: human embryonic stem cells (hESCs) and the more recently described induced pluripotent stem cells (iPSCs). Pluripotency means that these cells have the ability to form all the cells and tissues of the human body. hESC and iPSC differentiation into blood cells is particularly useful in studying the mechanisms of blood diseases and cell transfusion therapies. To better understand the potential of these cells to specifically produce blood cells, it is necessary to define an efficient and reproducible system of differentiation. Previously, our and other groups have used a stromal cell co-culture method to support blood development from hESCs. In these current studies, we are employing a stromal-free and serum-free differentiation method that may facilitate clinical translation of hESC- and iPSC-derived cells. This method involves forced aggregation of defined numbers of undifferentiated hESCs or iPSCs in 96-well plates by centrifugation to form embryoid bodies (spin EBs) of a uniform size. We examine this method’s potential to derive blood precursor cells and mature blood lineage cells from both hESCs and iPSCs.

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