The University of Colorado Denver is a public research university in the U.S. state of Colorado. It is part of the University of Colorado system. The university has two campuses — one in downtown Denver at the Auraria Campus, and the other at the Anschutz Medical Campus located in neighboring Aurora. The single university is the result of the 2004 consolidation of the University of Colorado at Denver and the University of Colorado Health science Center.The University of Colorado Denver is located on Auraria Campus in Downtown Denver, Colorado while the University of Colorado Hospital is located on the Anschutz Medical Campus in Aurora, Colorado nearly 10 miles away. UCH is also affiliated with the neighboring Children's Hospital, and with the National Jewish Medical and Research Center and Denver Health Medical Center in Denver. There are currently more than 27,000 students at the school's two physical campuses in downtown Denver and in Aurora. The school also offers classes via CU Online.The University of Colorado Denver is the largest research institution in Colorado, attracting more than $375 million in research grants annually, and granting more graduate degrees than any other institution in the state. CU Denver, along with University of Colorado Hospital and University Physicians, Inc., employs more than 12,200 Coloradans, making it one of the metro Denver area's top employers. The university serves more than 500,000 patients a year through its hospital and clinical services. Wikipedia.
Levin M.J.,University of Colorado at Denver
Current Opinion in Immunology | Year: 2012
Varicella-zoster virus (VZV) T-cell-mediated immunity (VZV-CMI) in older persons prevents latent VZV in sensory neurons from reactivating to cause herpes zoster. VZV-CMI declines greatly with aging, but can be restored by the licensed zoster vaccine. However, the vaccine-induced boost in VZV-CMI (which determines the efficacy of the vaccine) is a function of the age of the vaccinee, and the duration of this boost wanes with time. Both factors influence the value of this vaccine. To understand these aging effects, limited information about the phenotypic and functional differences in VZV-CMI in old and young persons are reviewed, as well as the reversal of these differences by vaccination. Based on information from these studies some potential approaches to improving prevention of herpes zoster are discussed. © 2012 Elsevier Ltd.
Hawkins J.L.,University of Colorado at Denver
New England Journal of Medicine | Year: 2010
A 30-year-old nulliparous woman at 39 weeks' gestation is undergoing induction of labor because of premature rupture of membranes. She is currently receiving an oxytocin infusion, and her cervical dilatation is 1 cm. Her obstetrician has ordered intermittent intravenous administration of fentanyl for pain relief, but she feels nauseated, has been unable to rest, and describes her pain as 9 on a scale of 10. The patient strongly prefers a vaginal delivery to cesarean delivery and is concerned that epidural analgesia may alter the progress of labor. The anesthesiologist is consulted to discuss the use of epidural analgesia during labor and delivery. Copyright © 2010 Massachusetts Medical Society. All rights reserved.
Szefler S.J.,University of Colorado at Denver
Journal of Allergy and Clinical Immunology | Year: 2011
Over the past 20 years, there has been a concerted effort in the United States to reduce morbidity related to chronic disease, including asthma. Attention was initially directed toward asthma in response to the recognition that asthma mortality was increasing and that the burden of disease was significant. These efforts to address asthma mortality led to many new initiatives to develop clinical practice guidelines, implement the asthma guidelines into clinical practice, conduct research to fill the gaps in the guidelines, and continuously revise the asthma guidelines as more information became available. An assessment of our progress shows significant accomplishments in relation to reducing asthma mortality and hospitalizations. Consequently, we are now at a crossroads in asthma care. Although we have recognized some remarkable accomplishments in reducing asthma mortality and morbidity, the availability of new tools to monitor disease activity, including biomarkers and epigenetic markers, along with information technology systems to monitor asthma control hold some promise in identifying gaps in disease management. These advances should prompt the evolution of new strategies and new treatments to further reduce disease burden. It now becomes imperative to continue a focus on ways to further reduce the burden of asthma and prevent its onset. © 2011 American Academy of Allergy, Asthma & Immunology.
Schedin P.,University of Colorado at Denver
Cold Spring Harbor perspectives in biology | Year: 2011
Cells of the mammary gland are in intimate contact with other cells and with the extracellular matrix (ECM), both of which provide not only a biochemical context, but a mechanical context as well. Cell-mediated contraction allows cells to sense the stiffness of their microenvironment, and respond with appropriate mechanosignaling events that regulate gene expression and differentiation. ECM composition and organization are tightly regulated throughout development of the mammary gland, resulting in corresponding regulation of the mechanical environment and proper tissue architecture. Mechanical regulation is also at play during breast carcinoma progression, as changes in ECM deposition, composition, and organization accompany breast carcinoma. These changes result in stiffer matrices that activate mechanosignaling pathways and thereby induce cell proliferation, facilitate local tumor cell invasion, and promote progression. Thus, understanding the role of forces in the mammary gland is crucial to understanding both normal developmental and pathological processes.
Vazquez-Torres A.,University of Colorado at Denver
Antioxidants and Redox Signaling | Year: 2012
Significance: The reactivity of the thiol in the side chain of cysteines is exploited by bacterial regulatory proteins that sense and respond to reactive oxygen and nitrogen species. Recent Advances: Charged residues and helix dipoles diminish the pKa of redox active cysteines, resulting in a thiolate that is stabilized by neighboring polar amino acids. The reaction of peroxides with thiolates generates a sulfenic acid (-SOH) intermediate that often gives rise to a reversible disulfide bond. Peroxide-induced intramolecular and intermolecular disulfides and intermolecular mixed disulfides modulate the signaling activity of members of the LysR/OxyR, MarR/OhrR, and RsrA family of transcriptional regulators. Thiol-dependent regulators also help bacteria resist the nitrosative and nitroxidative stress. -SOHs, mixed disulfides, and S-nitrosothiols are some of the post-translational modifications induced by nitrogen oxides in the thiol groups of OxyR and SsrB bacterial regulatory proteins. Sulfenylation, disulfide bond formation, S-thiolation, and S-nitrosylation are reversible modifications amenable to feedback regulation by antioxidant and antinitrosative repair systems. The structural and functional changes engaged in the thiol-dependent sensing of reactive species have been adopted by several regulators to foster bacterial virulence during exposure to products of NADPH phagocyte oxidase and inducible nitric oxide synthase. Critical Issues: Investigations with LysR/OxyR, MarR/OhrR, and RsrA family members have helped in an understanding of the mechanisms by which thiols in regulatory proteins react with reactive species, thereby activating antioxidant and antinitrosative gene expression. Future Directions: To define the determinants that provide selectivity of redox active thiolates for some reactive species but not others is an important challenge for future investigations. © 2012 Mary Ann Liebert, Inc.
Freedman R.,University of Colorado at Denver
Annual Review of Medicine | Year: 2014
α7-Nicotinic acetylcholine receptors have emerged as a potential therapeutic target for the treatment of neurocognitive dysfunctions in schizophrenia that are often resistant to existing antipsychotic drugs. Molecular evidence for involvement in schizophrenia of CHRNA7, the gene for the receptor subunit, in the neurobiology of deficits in attention is a critical rationale for the clinical study of α7-nicotinic receptor agonists to improve neurocognition. Initial clinical trials show enhancement of inhibitory neuron function related to sensory gating and increased attention and working memory, as well as improvement in negative symptoms such as anhedonia and alogia. Further development of this therapeutic strategy requires assessment of interactions with patients' heavy cigarette smoking and the relationship of this mechanism to the therapeutic effects of clozapine and olanzapine, both highly effective therapeutics with significant side effects. © 2014 by Annual Reviews. All rights reserved.
Nelson H.S.,University of Colorado at Denver
Journal of Allergy and Clinical Immunology: In Practice | Year: 2014
Subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) are both effective treatments for allergic rhinitis and allergic asthma, both show clinical evidence of disease modification by decreasing new sensitizations in individuals who were monosensitized, by reducing the development of asthma in patients with allergic rhinitis, and by inducing clinical improvement that persists for years after discontinuation of a successful course of treatment. Initiation of SLIT is accompanied by a high incidence of local symptoms, but these are generally mild and do not usually persist beyond the first few weeks. Systemic reactions do occasionally occur with SLIT but much less frequently than with SCIT, and, to date, no fatal or near fatal reactions have been reported. Effective doses have been defined for many allergens for SCIT and are now being defined for SLIT. There remains the unanswered question of the effectiveness of SLIT with multiple allergen extracts. The relative clinical efficacy of SCIT and SLIT remains to be defined. When each is compared with placebo, results of meta-analyses suggest greater efficacy of SCIT. In the limited number of randomized, head-to-head studies, SCIT has more often provided greater clinical and immunologic responses. However, head-to-head studies with well-defined effective doses by the 2 routes are urgently needed. © 2014 American Academy of Allergy, Asthma & Immunology.
Hendrick R.E.,University of Colorado at Denver
Radiology | Year: 2010
Purpose: To compare radiation doses and lifetime attributable risks (LARs) of radiation-induced cancer incidence and mortality from breast imaging studies involving the use of ionizing radiation. Materials and Methods: Recent literature on radiation doses from radiologic procedures and organ doses from nuclear medicine procedures, along with Biologic Effects of Ionizing Radiation (BEIR) VII age-dependent risk data, is used to estimate LARs of radiation-induced cancer incidence and mortality from breast imaging studies involving ionizing radiation, including screen-film mammography, digital mammography, digital breast tomosynthesis, dedicated breast computed tomography, breast-specific gamma imaging (BSGI), and positron emission mammography (PEM). Results: Two-view digital mammography and screen-film mammography involve average mean glandular radiation doses of 3.7 and 4.7 mGy, respectively. According to BEIR VII data, these studies are associated, respectively, with LARs of fatal breast cancer of 1.3 and 1.7 cases per 100 000 women aged 40 years at exposure and less than one case per one million women aged 80 years at exposure. Annual screening digital or screen-film mammography performed in women aged 40-80 years is associated with an LAR of fatal breast cancer of 20-25 cases in 100 000. A single BSGI study involving a label-recommended dose of 740-1100 MBq (20-30 mCi) of technetium 99m-sestamibi is estimated to involve an LAR of fatal cancer that is 20-30 times that of digital mammography in women aged 40 years. A single PEM study involving a labeled dose of 370 MBq (10 mCi) of fluorine 18 fluorodeoxyglucose is estimated to involve an LAR of fatal cancer that is 23 times higher than that of digital mammography in women aged 40 years. Conclusion: A single BSGI or PEM study is associated with a fatal radiation-induced cancer risk higher than or comparable to that of annual screening mammography in women aged 40-80 years. © RSNA, 2010.
Berman B.D.,University of Colorado at Denver
Brain : a journal of neurology | Year: 2013
Writer's cramp is a task-specific focal hand dystonia characterized by involuntary excessive muscle contractions during writing. Although abnormal striatal dopamine receptor binding has been implicated in the pathophysiology of writer's cramp and other primary dystonias, endogenous dopamine release during task performance has not been previously investigated in writer's cramp. Using positron emission tomography imaging with the D2/D3 antagonist 11C-raclopride, we analysed striatal D2/D3 availability at rest and endogenous dopamine release during sequential finger tapping and speech production tasks in 15 patients with writer's cramp and 15 matched healthy control subjects. Compared with control subjects, patients had reduced 11C-raclopride binding to D2/D3 receptors at rest in the bilateral striatum, consistent with findings in previous studies. During the tapping task, patients had decreased dopamine release in the left striatum as assessed by reduced change in 11C-raclopride binding compared with control subjects. One cluster of reduced dopamine release in the left putamen during tapping overlapped with a region of reduced 11C-raclopride binding to D2/D3 receptors at rest. During the sentence production task, patients showed increased dopamine release in the left striatum. No overlap between altered dopamine release during speech production and reduced 11C-raclopride binding to D2/D3 receptors at rest was seen. Striatal regions where D2/D3 availability at rest positively correlated with disease duration were lateral and non-overlapping with striatal regions showing reduced D2/D3 receptor availability, except for a cluster in the left nucleus accumbens, which showed a negative correlation with disease duration and overlapped with striatal regions showing reduced D2/D3 availability. Our findings suggest that patients with writer's cramp may have divergent responses in striatal dopamine release during an asymptomatic motor task involving the dystonic hand and an unrelated asymptomatic task, sentence production. Our voxel-based results also suggest that writer's cramp may be associated with reduced striatal dopamine release occuring in the setting of reduced D2/D3 receptor availability and raise the possibility that basal ganglia circuits associated with premotor cortices and those associated with primary motor cortex are differentially affected in primary focal dystonias.
Agency: NSF | Branch: Continuing grant | Program: | Phase: Cellular Dynamics and Function | Award Amount: 192.59K | Year: 2017
The goal of this CAREER project is to understand the molecular mechanism by which microtubule polymers assemble and how changes in the protein conformation lead to microtubule disassembly. Microtubule polymers play vital cellular roles in transport and signaling processes in all higher organisms. These processes depend on the ability of microtubules to switch between states of assembly and disassembly. To gain new insight into the mechanism of microtubule dynamics (assembly and disassembly), the research program will generate tubulin mutants that mimic sequence differences from cold-adapted organisms, which exhibit highly stable microtubules, and determine how these mutations impact microtubule dynamics. The results of these experiments will address a critical gap in our understanding of how changes in tubulin structure determine its propensity to assemble or disassemble, thereby providing a major advance for the microtubule field. In addition, this project will impact our broader understanding of molecular mechanisms of cold adaptation. To further broaden the impact of the project, the Principal Investigators laboratory will partner with students and teachers from Denver public high schools with underrepresented minority populations in a collaborative research-education program. This program will advance the research goals of the project while training high school teachers and students in the process of hypothesis-driven science, techniques in molecular biology, communication skills, and gaining exposure to the broader research community, thereby exciting and empowering future scientists.
This project will uniquely contribute to ongoing structural/function studies of tubulin proteins and microtubules. Whereas crystallographic approaches provide detailed molecular snapshots of stable conformations of the tubulin proteins, the projects genetic approach is uniquely suited to define the roles of dynamic regions of tubulins that are not accessible to crystallography. The Principal Investigator will use a combination of sequence data from cold tolerant organisms and unbiased genetic screens to identify amino acid changes that enhance microtubule stability, and to determine the basis of enhanced stability using in silico protein modeling and quantitative assays of microtubule activity in cells and in a minimal system with purified proteins.