| The Key Involvement of Poly(ADP-Ribosyl)ation in Defense Against Toxic Agents: Molecular Biology Studies |
MAY 2007 |
6 pages |
| Authors:
Mark E. Smulson; GEORGETOWN UNIV WASHINGTON DC SCHOOL OF MEDICINE
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 | Our study during the period 2005-2007 focused in lung cell as critical in the regulation of airway inflammation in response to environmental pollutants. |
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| The Key Involvement of Poly(ADP-ribosyl)ation in Defense Against Toxic Agents: Molecular Biology Studies |
30 OCT 2004 |
20 pages |
| Authors:
Mark Smulson; GEORGETOWN UNIV WASHINGTON DC SCHOOL OF MEDICINE
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| We observed that exposure of rat lung alveolar type II epithelial cells (RLE-6TN) to JP-8 in vitro induces biochemical and morphological markers of apoptotic cell death such as activation of caspase-3, cleavage of poly(ADP- ribose) polymerase, chromatin condensation, release of cytochrome c from mitochondria, and cleavage of genomic DNA. Generation of reactive oxygen species (ROS) and depletion of intracellular reduced glutathione (GSH) also showed to play important roles in the ... |
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| The Role of Src Tyrosine Kinase Signaling Networks in the Development and Progression of Ovarian Cancer in a Mouse Model |
SEP 2002 |
16 pages |
| Authors:
Christopher C. Taylor; Ting Chen; GEORGETOWN UNIV WASHINGTON DC SCHOOL OF MEDICINE
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| Ovarian cancer is among the most common and deadly malignancies in women, accounting for nearly 15,000 deaths per year in the United States. We have developed a mouse model of ovarian cancer, which will allow for new studies into the biochemical changes that occur in the tumorigenic process. We have determined that Src tyrosine kinase is over expressed and constitutively activated in these mouse ovarian cancer cells. This leads to ... |
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| The Key Involvement of Poly(ADP-Ribosylation) in Defense Against Toxic Agents: Molecular Biology Studies |
01 JUN 1998 |
23 pages |
| Authors:
Mark E. Smulson; GEORGETOWN UNIV WASHINGTON DC SCHOOL OF MEDICINE
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| The Air Force employs or generates a variety of materials, such as fuels, some of which may be potentially hazardous and could be released into the environment. Effective tools are required to predict and assess the fate of these agents in the environment. It is equally important, to understand the basic biological mechanisms, of these agents. We have thus begun to assess whether these fuels kill ... |
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| The Role of Interferon in the Cellular Response of the CNS Macrophage, the Microglia, During Injury and Inflammation |
09 OCT 97 |
6 pages |
| Authors:
Carol A. Colton; GEORGETOWN UNIV WASHINGTON DC SCHOOL OF MEDICINE
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| Our lab has studied the response of the CNS macrophage, the microglia to injury and inflammation. Using an in vitro approach, we have shown that microglia cultured from the cerebral cortices of neonatal animals (rat, mouse, hamster or human) have the same functional responses as non-CNS macrophages. That is, they demonstrate chemotaxis, express macrophage-like surface antigens and they produce a variety of cytoactive factors including proteases, interleukin-1 and reactive oxygen ... |
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| The Key Involvement of Poly (ADP-Ribosylation) in Defense against Toxic Agents. Molecular Biology Studies |
10 APR 95 |
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| Authors:
Mark E. Smulson; GEORGETOWN UNIV WASHINGTON DC SCHOOL OF MEDICINE
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 | Poly(ADP-ribose) polymerase (PARP) requires DNA for activity, and the catalytic activity of this enzyme is directly coordinated to the number of DNA strand breaks in DNA. Our laboratory, during an earlier AFOSR granting period was the first to isolate and clone a full-length cDNA for this enzyme. We also showed that this cDNA, in an appropriate vector, can be expressed in eukarvotic cells above endogenous levels. This has permitted direct ... |
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| The Key Involvement of Poly(ADP-Ribosylation) in Defense Against Toxic Agents: Molecular Biology Studies |
12 OCT 94 |
9 pages |
| Authors:
Mark E. Smulson; GEORGETOWN UNIV WASHINGTON DC SCHOOL OF MEDICINE
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| Poly(ADP-ribose) polymerase (PADPRP) is a chromatin-bound enzyme which is pivotal in cellular recovery from DNA strand break damage. PADPRP requires DNA for activity; it is significant that the catalytic activity of this enzyme is directly coordinated with the number of DNA strand breaks in DNA, both in vitro as well as in vivo. Thus, poly(ADP-ribosylation) is rapidly modulated in response to environmentally significant DNA-damaging agents; this probably represents the most ... |
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| The Key Involvement of Poly(ADP-Ribosylation) in Defense Against Toxic Agents: Molecular Biology Studies |
04 MAY 93 |
8 pages |
| Authors:
Mark E. Smulson; GEORGETOWN UNIV WASHINGTON DC SCHOOL OF MEDICINE
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| Our laboratory, during an earlier AFOSR granting period, was the first to isolate and clone a full-length cDNA for this enzyme. We also showed that this cDNA, in an appropriate vector, can be expressed in eukaryotic cells above endogenous levels. Accordingly, our laboratory is capable of performing direct experiments, utilizing recombinant DNA techniques, to test for the role of this enzyme in DNA repair and recovery from toxic agents during ... |
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| Studies of Safety, Infectivity and Immunogenicity of a New Temperature Sensitive (ts) 51-1 Strain of S. Typhi as a New Live Oral Typhoid Fever Vaccine Candidate, |
APR 1992 |
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| Authors:
J. A. Bellanti; B. J. Zeligs; S. Vetro; Y.H. Pung; S. Luccioli; GEORGETOWN UNIV WASHINGTON DC SCHOOL OF MEDICINE
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| This report describes the results of a phase 1 study evaluating the safety, infectivity, and immunogenicity of a new live oral S. typhi ts 51-1 typhoid fever vaccine in the human. Three normal male subjects ranging in age from 20-40 years received 3 oral doses of S. typhi ts 51-1, each dose containing 109 organisms. Prior to and following immunization each subject was carefully monitored by clinical and laboratory parameters ... |
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| Epidemiologic View of Allergic Diseases in North America: Implications for Aerospace Medicine, |
APR 1992 |
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| Authors:
J. A. Bellanti; GEORGETOWN UNIV WASHINGTON DC SCHOOL OF MEDICINE
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| The allergic disorders comprise a heterogeneous group of diseases which involve the respiratory tract (e.g. allergic rhinitis and asthma), the skin (e.g. atopic eczema), and the gastrointestinal tract (e.g. allergic gastroenteritis, food allergy) and which afflict 50 million Americans. The respiratory allergic diseases affect major segments of the population (15-170/0) who may be recruited as aircraft personnel and therefore these diseases pose particular risk to flying safety of personnel either ... |
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| The Key Involvement of Poly(ADP-Ribosylation) in Defense Against Toxic Agents in Molecular Biology Studies |
17 DEC 91 |
16 pages |
| Authors:
Mark E. Smulson; GEORGETOWN UNIV WASHINGTON DC SCHOOL OF MEDICINE
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| Poly(ADP-ribose) polymerase requires DNA for activity, and the catalytic activity of this enzyme is directly coordinated to the number of DNA strand breaks in DNA. Use of molecular techniques and the complete amino acid sequence of the enzyme, established during the past granting period, should allow us to learn considerably more about the mechanism and role of this enzyme in cells exposed to stressful environments. In AIM I. we proposed ... |
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| Nicotinic Cholinergic Receptors in Rat Brain |
26 MAR 91 |
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| Authors:
Kenneth J. Kellar; GEORGETOWN UNIV WASHINGTON DC SCHOOL OF MEDICINE
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| Nicotinic cholinergic receptors in rat brain were studied to determine their dependence on intact disulfide bonds, their relationship to catecholamine and serotonin axons, and their regulation by cholinesterase inhibitors and nicotinic agonists. Reduction of disulfide bonds with dithiothreitol decreased the number of nicotinic binding sites labeled by 3 Hacetylcholine (3 HAC). This effect was reversed by reoxidation of the reduced sulfhydryl groups to disulfide bonds. Lesioning catecholamine or serotonin axons ... |
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| The Key Involvement of Poly (ADP-Ribosylation) in Defense Against Toxic Agents in Molecular Biology Studies |
12 DEC 90 |
11 pages |
| Authors:
Mark E. Smulson; GEORGETOWN UNIV WASHINGTON DC SCHOOL OF MEDICINE
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| The enzyme poly(ADP-Rib) polymerase requires DNA for activity, and it is significant that the catalytic activity of this enzyme is directly coordinated to the number of DNA strand breaks in DNA, both in vitro as well as in vivo. Significant reductions in cellular NAD levels reflect increased poly ADP-ribosylation, due to DNA breaks, and hence it is of significance to this application that 38 organophosphorus and methyl carbonate insecticides in ... |
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| The Key Involvement of Poly (ADP-Ribosylation) in Defense against Toxic Agents in Molecular Biology Studies |
15 NOV 89 |
15 pages |
| Authors:
Mark E. Smulson; GEORGETOWN UNIV WASHINGTON DC SCHOOL OF MEDICINE
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| The program has 3 interrelated aims. The first stage involves recombinant construction of polymerase cDNA into a family of selected expression vectors which in most cases will possess an inducible promoter. During the first year, the cDNA was inserted in both sense and antisense orientations and also site-directed mutants. We were also concerned with construction (I-D) and expression of site-directed mutants and potential inhibitory peptides in vivo in order to ... |
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| The Development and Use of Anti-Receptor Antibodies to Induce Systemic Immunity to Organophosphorous Compounds |
01 NOV 89 |
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| Authors:
Tran C. Chanh; Philip Calcagno; GEORGETOWN UNIV WASHINGTON DC SCHOOL OF MEDICINE
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| A new soman (GD agent) analog was synthesized that contained an o- methyl group substitution at the fluorine position and a free amino group added on to the methyl group of the beta-carbon (C). This analog was conjugated to keyhole limpet hemocyanin (KLH) and use as immunogen in BALB/C mice to generate a monoclonal antibody (mAb), designated GD-1, specific for soman. The approximate IC50 of GD1 anti-soman mAb was 7 ... |
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| Nicotinic Cholinergic Receptors in Rat Brain |
01 MAY 86 |
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| Authors:
Kenneth J. Kellar; GEORGETOWN UNIV WASHINGTON DC SCHOOL OF MEDICINE
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| We have compared the characteristics of the recognition sites for 3Hacetylcholine and 3H(-)nicotine in rat brain and found that the pharmacology, distribution, disulfide bond requirement, and regulation by chronic administration of nicotine and soman are identical. From these studies we conclude that 3Hacetylcholine and 3H(-)nicotine recognize the same recognition site which has the characteristics expected of a nicotinic cholinergic receptor. We have also determined that 3Hacetylcholine of high specific radioactivity ... |
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| Nicotinic Cholinergic Receptors in Rat Brain |
13 MAY 85 |
11 pages |
| Authors:
Kenneth J. Kellar; GEORGETOWN UNIV WASHINGTON DC SCHOOL OF MEDICINE
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| We have conducted experiments to determine if 3H acetylcholine (3Hach) nicotinic recognition sites are located presynaptically on catecholamine and/or serotonin axons. Lesions of these axons by intraventricular injections of neurotoxins resulted in marked decreases in 3Hach binding sites in the striatum and hypothalamus, but not in the cortex or thalamus. These results indicate that 3Hach nicotinic binding sites are located on catecholamine and serotonin axons in specific areas of the ... |
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| Nicotinic Cholinergic Receptors in Rat Brain |
02 JUN 84 |
23 pages |
| Authors:
Kenneth J. Kellar; GEORGETOWN UNIV WASHINGTON DC SCHOOL OF MEDICINE
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| We have examined the molecular bond requirements of 3Hacetylcholine 3HACh nicotinic binding sites in rat brain. Reduction of disulfide bonds in vitro with the reducing agent dithiothreitol (DTT) resulted in a decrease in the number of 3HACh binding sites that could be measured, but the affinity of the remaining sites was unaltered. The effect of DTT was concentration-dependent, and it was reversed by reoxidation of the reduced disulfide bonds, with ... |
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