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In Vivo Characterization of Human APOA5 Haplotypes

Description: Increased plasma triglycerides concentrations are an independent risk factor for cardiovascular disease. Numerous studies support a reproducible genetic association between two minor haplotypes in the human apolipoprotein A5 gene (APOA5) and increased plasma triglyceride concentrations. We thus sought to investigate the effect of these minor haplotypes (APOA5*2 and APOA5*3) on ApoAV plasma levels through the precise insertion of single-copy intact APOA5 haplotypes at a targeted location in the mouse genome. While we found no difference in the amount of human plasma ApoAV in mice containing the common APOA5*1 and minor APOA5*2 haplotype, the introduction of the single APOA5*3 defining allele (19W) resulted in 3-fold lower ApoAV plasma levels consistent with existing genetic association studies. These results indicate that S19W polymorphism is likely to be functional and explain the strong association of this variant with plasma triglycerides supporting the value of sensitive in vivo assays to define the functional nature of human haplotypes.
Date: October 1, 2006
Creator: Ahituv, Nadav; Akiyama, Jennifer; Chapman-Helleboid, Audrey; Fruchart, Jamila & Pennacchio, Len A.
Partner: UNT Libraries Government Documents Department

Co-Funding for the Conference on Magnetic Resonance in Biological Systems

Description: The XXIst International Conference on Magnetic Resonance in Biological Systems (ICMRBS 2005), '60th anniversary of the discovery of Nuclear Magnetic Resonance,' was held between 16 and 21 January 2005 in Hyderabad, India. The meeting focused on a broad range of magnetic resonance methods as applied to studies of biological processes related to human health. The biennial ICMRBS has become the major venue for discussion of advances in nuclear and electron magnetic resonance (NMR & EMR/EPR) studies of the structure, dynamics, and chemical properties of important classes of biomolecules. Magnetic resonance has become an established tool in structural biology, and its special importance derives from its ability to provide atomic level information. It is becoming increasingly evident that the dynamic features of biomolecules, their intermolecular interactions, and accessible conformations in solution are data of key importance in understanding molecular recognition and function. NMR, which is already contributing to approximately 25% of the new structures being deposited with the Protein Data Bank, is destined to be a major player in the post genomic structure age with its emphasis on structure and function. In-vivo magnetic resonance spectroscopy (MRS) and magnetic resonance imaging (MRI) results shed light on human metabolic processes and on the cellular ramifications of cancer, stroke, cardiovascular disease, and other pathologies. New methodologies in metabonomics may lead to development of new drugs and medical diagnosis. The ICMRBS is the one conference that brings together experts from high-resolution NMR, solid state NMR, EPR, in-vivo MRS and MRI, and developers of instrumentation, techniques, software, and databases. Symposia at this ICMRBS are designed to continue the fruitful cross-fertilization of ideas that has been so successful in driving the spectacular advances in this field. ICMRBS 2005 maintained the traditional format of poster sessions, and plenary lectures that highlight major advances in each of the major ...
Date: October 1, 2008
Creator: Alan McLaughlin, Ph.D., Director, Division of Applied Science & Technology, NIBIB, NIH
Partner: UNT Libraries Government Documents Department

Acquisition, processing and display of gated cardiac scintigrams

Description: An improved method for non-traumatic and essentially noninvasive evaluation of left ventricular (LV) function with /sup 99m/Tc as the tracer was developed. This method combines previously used EKG gating techniques for cardiac blood pool visualization with new computerized acquisition, processing and display techniques. An Anger camera, a small computer, and a physiological synchronizer are used to acquire a sequence of eight scintigrams which span the entire cardiac cycle. Under our present protocol two twenty-minute sequences are obtained, one an LAO (50$sup 0$) projection, the other an RAO (30$sup 0$) projection. Subsequently these images are processed on-line with a digital filter to increase definition of the cardiac borders. The eight images are then displayed sequentially on a specially designed electronic monitor to give an impression of the beating heart somewhat analogous to that obtained with invasive contrast angiography. (auth)
Date: January 1, 1974
Creator: Alpert, N. M.; Chesler, D. A.; McKusick, K. A.; Potsaid, M. S.; Pohost, G. M. & Dinsmore, R. A.
Partner: UNT Libraries Government Documents Department

Ethical and legal issues arising from complex genetic disorders. DOE final report

Description: The project analyzed the challenges raised by complex genetic disorders in genetic counselling, for clinical practice, for public health, for quality assurance, and for protection against discrimination. The research found that, in some settings, solutions created in the context of single gene disorders are more difficult to apply to complex disorders. In other settings, the single gene solutions actually backfired and created additional problems when applied to complex genetic disorders. The literature of five common, complex genetic disorders--Alzheimer's, asthma, coronary heart disease, diabetes, and psychiatric illnesses--was evaluated in depth.
Date: October 9, 2002
Creator: Andrews, Lori
Partner: UNT Libraries Government Documents Department

Physiopathology of blood platelets and development of platelets substitutes. Progress report, August 1, 1976--October 31, 1977. [/sup 51/Cr]

Description: Progress is reported on the following research projects: the effect of estrogen on platelet aggregability and thrombus formation; the antithrombotic effect of platelet inhibiting agents in a bench model of artificial kidney; the arrest of hemorrhage in severely alloimmunized thrombocytopenic patients; and in vivo elution of /sup 51/Cr from labeled platelets induced by antibody. (HLW)
Date: July 31, 1977
Creator: Baldini, M G
Partner: UNT Libraries Government Documents Department

Rubidium-81 used as a myocardium imaging agent

Description: From 11th international annual meeting of the German Society of Nuclear Medicine; Athens, Greece (24 Sep 1973). Rubidium-81 is a new myocardial imaging agent with an ideal T/sub 1/2 of 4.6 hr and energies acceptable for gamma-camera viewing. The target-to-nontarget ratio for heart image to background in the projection images is usually less than 2: 1, thus good statistics are necessary to delineate lesions. The low radiation dose and availability of this isotope allow one to obtain 6 to 10 times the data, and /sup 81/Rb is probably superior to /sup 129/Cs and /sup 43/K for myoca rdial imaging if adequate collimation is present. (auth)
Date: September 1, 1973
Creator: Budinger, T.F.; Yano, Y. & McRae, J.
Partner: UNT Libraries Government Documents Department

Raman Spectroscopic Analysis of Biochemical Changes in Individual Triglyceride-Rich Lipoproteins in the Pre- and Postprandial State

Description: Individual triglyceride-rich lipoprotein (TGRL) particles derived from human volunteers are non-destructively analyzed by laser tweezers Raman microspectroscopy and information on their composition and distribution is obtained. The Raman signature of single optically trapped very low-density lipoproteins (VLDL), a subclass of TGRL, which play an important role in cardiovascular disease, exhibits distinct peaks associated with molecular vibrations of fatty acids, proteins, lipids, and structural rearrangements of lipids. Our analysis of pre- and postprandial VLDL exhibits the signature of biochemical changes in individual lipoprotein particles following the consumption of meals. Interaction of VLDL with endothelium leads to the breakdown of complex triacylglycerols and the formation of a highly ordered core of free saturated fatty acids in the particle. A particle distribution analysis reveals trends in the degree to which this process has occurred in particles at different times during the postprandial period. Differences in particle distributions based on the different ratios of polyunsaturated to saturated fats in the consumed meals are also easily discerned. Individual lipoprotein particles hydrolyzed in-vitro through addition of lipoprotein lipase (LpL) exhibit strikingly similar changes in their Raman spectra. These results demonstrate the feasibility of monitoring the dynamics of lipid metabolism of individual TGRL particles as they interact with LpL in the endothelial cell wall using Raman spectroscopy.
Date: September 13, 2004
Creator: Chan, J; Motton, D; Rutledge, J; Keim, N & Huser, T
Partner: UNT Libraries Government Documents Department

Ernest Orlando Berkeley National Laboratory - Fundamental and applied research on lean premixed combustion

Description: Ernest Orland Lawrence Berkeley National Laboratory (Berkeley Lab) is the oldest of America's national laboratories and has been a leader in science and engineering technology for more than 65 years, serving as a powerful resource to meet Us national needs. As a multi-program Department of Energy laboratory, Berkeley Lab is dedicated to performing leading edge research in the biological, physical, materials, chemical, energy, environmental and computing sciences. Ernest Orlando Lawrence, the Lab's founder and the first of its nine Nobel prize winners, invented the cyclotron, which led to a Golden Age of particle physics and revolutionary discoveries about the nature of the universe. To this day, the Lab remains a world center for accelerator and detector innovation and design. The Lab is the birthplace of nuclear medicine and the cradle of invention for medical imaging. In the field of heart disease, Lab researchers were the first to isolate lipoproteins and the first to determine that the ratio of high density to low density lipoproteins is a strong indicator of heart disease risk. The demise of the dinosaurs--the revelation that they had been killed off by a massive comet or asteroid that had slammed into the Earth--was a theory developed here. The invention of the chemical laser, the unlocking of the secrets of photosynthesis--this is a short preview of the legacy of this Laboratory.
Date: July 7, 1999
Creator: Cheng, Robert K.
Partner: UNT Libraries Government Documents Department

Heart pathology determination from electrocardiogram signals by application of deterministic chaos mathematics. CRADA final report

Description: It is well known that the electrical signals generated by the heart exhibit nonlinear, chaotic dynamics. A number of heart pathologies alter heartbeat dynamics and/or the electrical properties of the heart, which, in turn, alter electrocardiogram signals. Electrocardiogram techniques in common use for diagnosing pathologies have limited sensitivity and specificity. This leads to a relatively high misdiagnosis rate for ventricular fibrillation. It is also known that the linear analysis tools utilized (such as fast Fourier transforms and linear statistics) are limited in their ability to find subtle changes or characteristic signatures in nonlinear chaotic electrocardiogram signals. In contrast, the authors` research indicates that chaotic time-series analysis tools that they have developed allow quantification of the nonlinear nature of dynamic systems in the form of nonlinear statistics, and also enable characteristic signatures to be identified. The goal of this project is to modify these tools to increase and enhance the medically useful information obtained from electrocardiogram signals through the application of chaotic time series analysis tools. In the one year of the project, the tools have been extended to enhance the capabilities for detecting ventricular fibrillation. Chaotic time-series analysis provides a means to increase sensitivity in detecting general heart dynamics. Oak Ridge National Laboratory specialists have worked with Physio-Control and their medical collaborators to extend the capabilities of state-of-the-art electrocardiogram systems and interpretation of results.
Date: March 1, 1999
Creator: Clapp, N.E.; Hively, L.M. & Stickney, R.E.
Partner: UNT Libraries Government Documents Department

Use of tree-based models to identify subgroups and increase power to detect linkage to cardiovascular disease traits

Description: This article discusses the use of tree-based models to identify subgroups and increase power to detect linkage to cardiovascular disease traits.
Date: December 31, 2003
Creator: Costello, Tracy Jennifer; Swartz, Michael D.; Sabripour, Mahyar; Gu, Xiangjun; Sharma, Rishika & Etzel, Carol J.
Partner: UNT College of Arts and Sciences

Labeling cellular elements of blood with Technetium-99m

Description: The purpose of this proposal is to develop new technique of labeling platelets and white cells with Tc-99m radionuclide. The conditions of labeling canine platelets and white cells with the lipid-soluble Tc-99m HMPAO have been optimized. The function of labeled platelets were evaluated by the determination of platelet survival time and recovery and these values were compared with that of In-111 tropolone labeled platelets. We developed the bilateral femoral catheterization model for the evaluation of platelet-thrombosis on control and heparin-bonded catheters in dogs. We are evaluating platelet thrombosis in the hollow-fiber hemodialyzer with Tc-99m and In-111 labeled platelets. We have developed the flow-loop for in vitro studies and are using a pig model for quantitation of platelet-consumption during hemodialysis. We are currently evaluating the new technique of platelet and white cell-labeling with Tc-99m and testing them in animal models of thrombosis and infection (osteo-myelitis). We are also using the Tc-99m HMPAO labeled mixed white cells in the early diagnosis (3-hour post-injection) of acute and chronic infection in patients and comparing the results with that of IN-111 oxine labeled white cells.
Date: August 1, 1990
Creator: Dewanjee, M.K.
Partner: UNT Libraries Government Documents Department

Platelet thrombosis in cardiac-valve prostheses

Description: The contribution of platelets and clotting factors in thrombosis on cardiovascular prostheses had been quantified with several tracers. Thrombus formation in vivo could be measured semiquantitatively in animal models and patients with indium-111, Technetium-99m labeled platelets, iodine-123, iodine-131 labeled fibrinogen, and In-111 and Tc-99m labeled antibody to the fibrinogen-receptor on the platelet- membrane, or fibrin. The early studies demonstrated that certain platelet-inhibitors, e.g. sulfinpyrazone, aspirin or aspirin- persantine increased platelet survival time with mechanical valves implanted in the baboon model and patients. Thrombus localization by imaging is possible for large thrombus on thrombogenic surface of prosthesis in the acute phase. The majority of thrombus was found in the sewing ring (Dacron) in the acute phase in both the mechanical and tissue valves. The amount of retained thrombus in both mechanical and tissue valves in our one-day study in the dog model was similar (< 1% if injected In-111 platelets = 5 billion platelets). As the fibrous ingrowth covered the sewing ring, the thrombus formation decreased significantly. Only a small amount of thrombus was found on the leaflets at one month in both the dog and calf models. 38 refs., 9 figs., 5 tabs.
Date: January 1, 1989
Creator: Dewanjee, M.K.
Partner: UNT Libraries Government Documents Department

Studies defining interactions between hypertension and air pollutants

Description: An animal model of hypertension was developed by breeding two lines of rats. The model was used to investigate interactions between commonly encountered air pollutants and the development of hypertension. This paper summarizes studies of the interaction of sulfur dioxide and ozone with the models. (ACR)
Date: January 1, 1980
Creator: Drew, R T; Costa, D L; Haber, S & Iwai, J
Partner: UNT Libraries Government Documents Department

Applications of CdTe to nuclear medicine. Annual report, February 1, 1979-January 31, 1980

Description: The application of CdTe gamma detectors in nuclear medicine is reported on. An internal probe was developed which can be inserted into the heart to measure the efficiency of various radiopharmaceuticals in the treatment of heart attacks. A second application is an array of detectors which is light enough to be worn by ambulatory patients and can measure the change in cardiac output over an eight hour period during heart attack treatment. The instrument includes an on board tape recorder. (ACR)
Date: January 1, 1980
Creator: Entine, G
Partner: UNT Libraries Government Documents Department

Comparison of positron tomography and scintigraphy with $sup 201$Tl for delineation of the myocardium

Description: Recent advances in nuclear medicine instrumentation have led to the development of improved positron-imaging systems which exceed in performance the earlier systems which were limited mainly by low count rate capability. This has led to renewed interest in positron imaging in general, primarily because such devices offer better resolution and higher sensitivity than conventional, mechanically collimated gamma cameras, as well as tomographic capability which may provide additional and more accurate information for the clinician. Furthermore, the unique capabilities of positrons for use in reconstructive imaging are beginning to be exploited. In the present report, results are presented from a preliminary study in which longitudinal tomographic myocardial images, produced with $sup 81$Rb as the positron-emitting label using the double camera coincidence system are compared with conventional myocardial images obtained with $sup 201$Tl and a gamma camera. (auth)
Date: January 1, 1976
Creator: Fill, H.; Buchin, M.; Harper, P.V.; Muehllehner, G.; Walsh, W.; Resnekov, L. et al.
Partner: UNT Libraries Government Documents Department

Consistency of reported health effects of air pollution

Description: Three different studies have considered the relation between various mortality rates and air pollution levels. this paper evaluates the consistency of these studies and finds some evidence of a constant proportional effect on both males and females. Two of the studies indicate a relation between air pollution and total mortality rate but differ in the estimate of the effect by a factor of fifteen. The studies generally find little relation between pollution and lung diseases and lung cancer; they disagree on heart disease and total cancer findings.
Date: unknown
Creator: Finch, S J & Morris, S C
Partner: UNT Libraries Government Documents Department


Description: There is overwhelming evidence that addiction is a disease of the brain (Leshner, 1997). Yet public perception that addiction is a reflection of moral weakness or a lack of willpower persists. The insidious consequence of this perception is that we lose sight of the fact that there are enormous medical consequences of addiction including the fact that a large fraction of the total deaths from cancer and heart disease are caused by smoking addiction. Ironically the medical school that educates physicians in addiction medicine and the cancer hospital that has a smoking cessation clinic are vanishingly rare and efforts at harm reduction are frequently met with a public indignation. Meanwhile the number of people addicted to substances is enormous and increasing particularly the addictions to cigarettes and alcohol. It is particularly tragic that addiction usually begins in adolescence and becomes a chronic relapsing problem and there are basically no completely effective treatments. Clearly we need to understand how drugs of abuse affect the brain and we need to be creative in using this information to develop effective treatments. Imaging technologies have played a major role in the conceptualization of addiction as a disease of the brain (Fowler et al., 1998a; Fowler et al., 1999a). New knowledge has been driven by advances in radiotracer design and chemistry and positron emission tomography (PET) instrumentation and the integration of these scientific tools with the tools of biochemistry, pharmacology and medicine. This topic cuts across the medical specialties of neurology, psychiatry, cancer and heart disease because of the high medical, social and economic toll that drugs of abuse, including and especially the legal drugs, cigarettes and alcohol, take on society. In this chapter we will begin by highlighting the important role that chemistry has played in making it possible to quantitatively image the movement ...
Date: January 29, 2001
Creator: Fowler, J. S.; Volkow, N. D.; Ding, Y. S.; Logan, J. & Wang, G. J.
Partner: UNT Libraries Government Documents Department

Relation of air pollution to mortality: a critique. [SO/sub 2/ in New York City air]

Description: A study of the relation between SO/sub 2/ and smoke-shade in the surface air of New York City and deaths resulting from respiratory and heart diseases is discussed. The need to use data from a number of sampling stations in any epidemiological study on the health effects of air pollutants is stressed. It is pointed out that the complicated effects of weather on the environmental transport of air pollutants and the variations in statistical methods used may lead to eronious conclusions as to the cause of deaths.
Date: December 1, 1977
Creator: Goldstein, I F; Goldstein, M & Landovitz, L
Partner: UNT Libraries Government Documents Department

Interactive radiopharmaceutical facility between Yale Medical Center and Brookhaven National Laboratory. Progress report, November 1, 1980-October 31, 1981

Description: Research conducted in three principal areas is discussed and summarized. (1) Investigation of the influence of antiarrhythmic agents, such as lidocaine and procainamide, on the chemotaxis and nylon fiber adherence of indium-111-labelled human polymorphonulcear leukocytes (PMNs) in vitro revealed that at normal therapeutic levels of lidocaine and procaine, the adherence and chemotactic function of In-111-PMNs remain unaltered. Results with higher therapeutic blood levels are also discussed. (2) An improved method for labeling human platelets with In-111-oxine is outlined, and the influence of centrifugal force, oxine, ethanol, and radiation on platelet function is reported. Results indicate that normal labeling procedures induce no gross changes in platelet function. (3) The chemical preparation of radioiodinated arachidonic acid (AA) and nonradioactive acid ester of AA, and the analysis of metabolites of these compounds following myocardial ischemia were investigated in dogs. The tissue uptake of /sup 131/I-AA was compared to that of thallium-201.
Date: unknown
Creator: Gottschalk, A.
Partner: UNT Libraries Government Documents Department

What has happened to the survivors of the early Los Alamos nuclear accidents

Description: Two nuclear accidents involving a plutonium sphere just subcritical in size occurred at the Los Alamos Laboratory, LA-1 in 1945 and LA-2 in 1946. Because remote control devices were deemed unreliable at the time, the tamper material (tungsten carbide bricks in LA-1 and beryllium hemispheres in LA-2) was added by hand with the operator standing next to the assembly. In each case the critical size of the assembly was accidentally exceeded and the resultant exponentially increasing chain reaction emitted a burst of neutrons and gamma rays. Ten persons were exposed to the radiation bursts which were largely composed of neutrons. The doses ranged from fatal in the case of the two operators, to small in the case of some survivors. The two operators died within weeks as a result of acute radiation injury. Only six of the eight survivors were available for follow-up study ten or more years after the accident. Four of these six survivors are now dead, but the two living survivors are in excellent health with no clinical or laboratory evidence of late radiation injury. Two of the deceased died of acute myelogenous leukemia, another died at age 83 of refractory anemia, and the fourth of myocardial infarction. The heart attack could have been precipitated by the myxedema assumed to have been the result of the radiation exposure.
Date: January 1, 1979
Creator: Hempelman, L.H.; Lushbaugh, C.C. & Voelz, G.L.
Partner: UNT Libraries Government Documents Department

Genetic influence on brain catecholamines: high brain norepinephrine in salt-sensitive rats

Description: Rats genetically sensitive to salt-induced hypertension evinced higher levels of plasma norepinephrine and epinephrine than rats genetically resistant to hypertension. The hypertension-sensitive rats showed higher hypothalamic norepinephrine and lower epinephrine than resistant rats. In response to a high salt diet, brain stem norepinephrine increased in sensitive rats while resistant rats exhibited a decrease on the same diet.
Date: January 1, 1980
Creator: Iwai, J; Friedman, R & Tassinari, L
Partner: UNT Libraries Government Documents Department

Diagnostic and therapeutic applications of diode lasers and solid state lasers in medicine

Description: The Texas Medical Center in Houston and the nearby UT Medical Branch at Galveston together constitute a major center of medical research activities. Laser applications in medicine are under development with the engineering assistance of the colloborating engineering centers at Rice University, UT-Austin, and Texas A M Univ. In addition, this collective is collaborating with the Naval Research Laboratory, where new developments in laser design are underway, in order to transfer promising new laser technology rapidly into the medical environment.
Date: May 1, 1992
Creator: Jacques, S.L. (Texas Univ., Houston, TX (United States). Cancer Center); Welch, A.J. (Texas Univ., Austin, TX (United States)); Motamedi, M. (Texas Univ., Galveston, TX (United States). Medical Branch); Rastegar, S. (Texas A and M Univ., College Station, TX (United States)); Tittel, F. (Rice Univ., Houston, TX (United States)) & Esterowitz, L. (Naval Research Lab., Washington, DC (United States))
Partner: UNT Libraries Government Documents Department