Department of Medicine

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    Effects of Purified Myosin Light Chain Kinase on Myosin Light Chain Phosphorylation and Catecholamine Secretion in Digitonin-Permeabilized Chromaffin Cells
    (Plenum, 1987-04-01) Lee, Sung A.; Hoiz, Ronald W.; Hathaway, David R.; Medicine, School of Medicine
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    Intracranial placement of a nasogastric tube
    (American Society of Neuroradiology, 1989) Koch, K.J.; Becker, G.J.; Edwards, M.K.; Hoover, R.L.; Medicine, School of Medicine
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    Antisense Oligonucleotides from the Stage-specific Myeloid Zinc Finger Gene MZF-1 Inhibit Granulopoiesis In Vitro
    (Rockefeller University Press, 1991-11-01) Bavisotto, Linda; Kaushansk, Kenneth; Lin, Nancy; Hromas, Robert; Medicine, School of Medicine
    Zinc finger proteins are transcriptional regulators of other genes, often controlling developmental cascades of gene expression. A recently cloned zinc finger gene, MZF-1, was found to be preferentially expressed in myeloid cells. Using complementary radiolabeled MZF-1 RNA hybridized to human bone marrow smears in situ, it was discovered that the expression of MZF-1 is essentially limited to the myelocyte and metamyelocyte stages of granulopoiesis. Antisense but not sense oligonucleotides from MZF-1 significantly inhibited granulocyte colony-stimulating factor-driven granulocyte colony formation in vitro.
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    Opioid peptides
    (The National Institute on Alcohol Abuse and Alcoholism, 1997) Froehlilch, Janice C.; Medicine, School of Medicine
    Opioid peptides produced in the body act as neuromodulators that modify the actions of other neurotransmitters in the central nervous system. By altering the electrical properties of their target neurons, thereby making these neurons more difficult to excite, opioid peptides can influence the release of various neurotransmitters. As a result of this modulation, opioid peptides can--among other functions--induce pain relief and euphoria as well as affect certain behaviors, including alcohol consumption. Alcohol can activate the opioid peptide system. This mechanism may contribute to alcohol reinforcement and excessive alcohol consumption, because agents that inhibit the opioid peptide system decrease alcohol self-administration in animals and reduce craving and alcohol consumption in human alcoholics. Moreover, a genetically determined, increased responsiveness of the opioid system to alcohol may contribute to a predisposition for alcoholism in some people.
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    Alcohol and medication interactions
    (U.S. National Institute on Alcohol Abuse and Alcoholism, 1999) Weathermon, Ron; Crabb, David W.; Medicine, School of Medicine
    Many medications can interact with alcohol, thereby altering the metabolism or effects of alcohol and/or the medication. Some of these interactions can occur even at moderate drinking levels and result in adverse health effects for the drinker. Two types of alcohol-medication interactions exist: (1) pharmacokinetic interactions, in which alcohol interferes with the metabolism of the medication, and (2) pharmacodynamic interactions, in which alcohol enhances the effects of the medication, particularly in the central nervous system (e.g., sedation). Pharmacokinetic interactions generally occur in the liver, where both alcohol and many medications are metabolized, frequently by the same enzymes. Numerous classes of prescription medications can interact with alcohol, including antibiotics, antidepressants, antihistamines, barbiturates, benzodiazepines, histamine H2 receptor antagonists, muscle relaxants, nonnarcotic pain medications and anti-inflammatory agents, opioids, and warfarin. In addition, many over-the-counter and herbal medications can cause negative effects when taken with alcohol.
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    Efficient in vivo catheter-based pericardial gene transfer mediated by adenoviral vectors
    (Wiley, 1999-01) March, K.L.; Woody, M.; Mehdi, K.; Zipes, D.P.; Brantly, M.; Trapnell, B.C.; Medicine, School of Medicine
    Adenoviral vectors are promising agents for a number of in vivo gene therapy applications including diseases of the heart and coronary vessels. Efficient intravascular gene transfer to specific sites has been achieved in occluded vessels, but otherwise is hampered by the effect of blood flow on localized vector uptake in the vessel wall. An alternative delivery approach to coronary arteries is the expression of diffusible gene products into the pericardial space surrounding the heart and coronary arteries. However, in vivo pericardial access is comparatively difficult and has been limited to surgical approaches. We hypothesized that efficient adenovirus-mediated gene expression in pericardial lining mesothelium could be achieved by transmyocardial vector delivery to the pericardium. To evaluate this concept, a hollow, helical-tipped penetrating catheter was used to deliver vector-containing fluid directly into the intrapericardial space. The catheter was introduced percutaneously in anesthetized mongrel dogs, advanced into the right ventricle, and the tip passed through the apical right ventricular myocardium under direct radiographic visualization until the open end of the catheter tip resided in the intrapericardial space. Adenoviral vectors expressing either nuclear-localizing beta-galactosidase, cytoplasmic luciferase, or secreted human alpha 1AT reporters (Av1nBg, Av1Lu, or Av1Aa, respectively) were instilled through the catheter into the intrapericardial space. Three days later the animals were sacrificed and reporter gene expression was evaluated in pericardium, epicardium, and multiple other tissues. In animals receiving Av1nBg, beta-galactosidase activity was evident in most of the pericardial lining endothelium, up to 100% in many areas. In animals receiving Av1Lu, luciferase reporter activity was abundant in pericardial tissues, but near-background levels were observed in other organs. In animals receiving Av1Aa, human alpha 1AT was abundant (16-29 mg/ml) in pericardial fluid, but was undetectable in serum. All animals tolerated the procedure well with no electrocardiographic changes and no clinical sequelae. These observations demonstrate highly efficient adenovirus vector delivery and gene transfer and expression in the pericardium and support the feasibility of localized gene therapy via catheter-based pericardial approaches. We suggest that the pericardial sac may serve as a sustained-release protein delivery system for the generation of desired gene products or their metabolites for diffusion into the epicardial region.
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    Establishment of a clinically correlated human pericardial fluid bank: Evaluation of intrapericardial diagnostic potential
    (Wiley, 1999-01) Dickson, Tonya J.; Nguyen, A.Q.; Kumfer, K.; Maxted, W.; Gurudutt, Vivek; Brown, John; Mahomed, Yousuf; Sharp, Thomas; Aufiero, Thomas X.; Fineberg, Naomi; March, Keith L.; Medicine, School of Medicine
    The development of a clinically correlated human pericardial fluid bank and database is described. A unique feature of this registry is the availability of a large number of pericardial fluid samples for testing with respect to multiple factors and for correlation with angiographic findings and clinical syndromes expressed by the patients. The collection of data at the present time comprises frozen pericardial fluid samples obtained from patients who have undergone cardiac surgery; and historical, clinical, and laboratory data obtained from the patient records. Nearly 400 samples have been stored and analyzed thus far, with sample entry continuing. This registry is designed to evaluate the local factors that play a role in mediating or reflecting myocardial or coronary responses. Pathophysiologic processes of particular interest include restenosis, plaque ruptures, and angiogenesis. Study of the pericardial fluid bank should lead to enhanced understanding of molecular mechanisms, as well as to the explanation for the reasons underlying interpatient variability in these processes. It is further anticipated that this information might provide a foundation for the diagnostic use of pericardial fluid to individualize therapies targeting angiogenesis or plaque physiology.
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    Selected lines and inbred strains. Tools in the hunt for the genes involved in alcoholism
    (The National Institute on Alcohol Abuse and Alcoholism, 2000) Grahame, Nicholas J.; Medicine, School of Medicine
    In their quest to elucidate the genetic influences contributing to alcoholism, researchers have long used selected lines and inbred strains of rodents. Selected lines are obtained by repeatedly mating those animals within a population that show extremely high or low values of the desired trait. Inbred strains are generated by mating male and female siblings, irrespective of any particular trait, over several generations. Both of these approaches have provided researchers with extensive knowledge about the genetic and neurobiological mechanisms contributing to alcohol-related traits. However, the use of these models is associated with some limitations, mostly resulting from the inbreeding involved in generating such lines and strains. Nevertheless, these models can offer some advantages over other genetic approaches, such as the analysis of quantitative trait loci or the generation of transgenic and knockout mice.
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    Optical Aberrations and Objective Choice in Multicolor Confocal Microscopy
    (Future Science, 2000-03) Dunn, Kenneth W.; Wang, Exing; Medicine, School of Medicine
    Refinements in design have simplified confocal microscopy to the extent that it has become a standard research tool in cell biology. However, as confocal microscopes have become more powerful, they have also become more demanding of their optical components. In fact, optical aberrations that cause subtle defects in image quality in wide-field microscopy can have devastating effects in confocal microscopy. Unfortunately, the exacting optical requirements of confocal microscopy are often hidden by the optical system that guarantees a sharp image, even when the microscope is performing poorly. Optics manufacturers provide a wide range of microscope objectives, each designed for specific applications. This report demonstrates how the trade-offs involved in objective design can affect confocal microscopy.
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    Nutrition Management of Type 2 Diabetes by Primary Care Physicians
    (2000-11) Marrero, David G.; Kraft, Stephanie Kakos; Mayfield, Jennifer; Wheeler, Madelyn L.; Fineberg, Naomi
    A survey was mailed to a probability sample of primary care physicians in Indiana to assess their use of and barriers to nutritional therapy for patients with type 2 diabetes. Most (62%) primary care physicians reported referring their type 2 diabetes patients for nutrition counseling, while 38% reported providing counseling themselves. Patient-centered barriers were most frequently cited as reasons for poor effectiveness of nutrition therapy. This differs from previous research that cites system-level factors as barriers.