Showing papers by "Research Triangle Park published in 1996"

Research needs for the risk assessment of health and environmental effects of endocrine disruptors: a report of the U.S. EPA-sponsored workshop.

Abstract: The hypothesis has been put forward that humans and wildlife species adverse suffered adverse health effects after exposure to endocrine-disrupting chemicals. Reported adverse effects include declines in populations, increases in cancers, and reduced reproductive function. The U.S. Environmental Protection Agency sponsored a workshop in April 1995 to bring together interested parties in an effort to identify research gaps related to this hypothesis and to establish priorities for future research activities. Approximately 90 invited participants were organized into work groups developed around the principal reported health effects-carcinogenesis, reproductive toxicity, neurotoxicity, and immunotoxicity-as well as along the risk assessment paradigm-hazard identification, dose-response assessment, exposure assessment, and risk characterization. Attention focused on both ecological and human health effects. In general, group felt that the hypothesis warranted a concerted research effort to evaluate its validity and that research should focus primarily on effects on development of reproductive capability, on improved exposure assessment, and on the effects of mixtures. This report summarizes the discussions of the work groups and details the recommendations for additional research.

Benzothiadiazole, a novel class of inducers of systemic acquired resistance, activates gene expression and disease resistance in wheat.

Abstract: Systemic acquired resistance is an important component of the disease resistance repertoire of plants. In this study, a novel synthetic chemical, benzo(1,2,3)thiadiazole-7-carbothioic acid S-methyl ester (BTH), was shown to induce acquired resistance in wheat. BTH protected wheat systemically against powdery mildew infection by affecting multiple steps in the life cycle of the pathogen. The onset of resistance was accompanied by the induction of a number of newly described wheat chemically induced (WCI) genes, including genes encoding a lipoxygenase and a sulfur-rich protein. With respect to both timing and effectiveness, a tight correlation existed between the onset of resistance and the induction of the WCI genes. Compared with other plant activators, such as 2,6-dichloroisonicotinic acid and salicylic acid, BTH was the most potent inducer of both resistance and gene induction. BTH is being developed commercially as a novel type of plant protection compound that works by inducing the plant's inherent disease resistance mechanisms.

Benzothiadiazole induces disease resistance in Arabidopsis by activation of the systemic acquired resistance signal transduction pathway

Abstract: Summary Benzothiadiazole (BTH) is a novel chemical activator of disease resistance in tobacco, wheat and other important agricultural plants. In this report, it is shown that BTH works by activating SAR in Arabidopsis thaliana. BTH-treated plants were resistant to infection by turnip crinkle virus, Pseudomonas syringae pv ‘tomato’ DC3000 and Peronospora parasitica. Chemical treatment induced accumulation of mRNAs from the SAR-associated genes, PR-1, PR-2 and PR-5. BTH treatment induced both PR-1 mRNA accumulation and resistance against P. parasitica in the ethylene response mutants, etr1 and ein2, and in the methyl jasmonate-insensitive mutant, jar1, suggesting that BTH action is independent of these plant hormones. BTH treatment also induced both PR-1 mRNA accumulation and P. parasitica resistance in transgenic Arabidopsis plants expressing the nahG gene, suggesting that BTH action does not require salicylic acid accumulation. However, because BTH-treatment failed to induce either PR-1 mRNA accumulation or P. parasitica resistance in the non-inducible immunity mutant, nim1, it appears that BTH activates the SAR signal transduction pathway.

A benzothiadiazole derivative induces systemic acquired resistance in tobacco

Abstract: Summary Systemic acquired resistance (SAR) is a pathogen-induced disease resistance response in plants that is characterized by broad spectrum disease control and an associated coordinate expression of a set of SAR genes. Benzo(1,2,3)-thiadiazole-7-carbothioic acid S-methyl ester (BTH) is a novel synthetic chemical capable of inducing disease resistance in a number of dicotyledenous and monocotyledenous plant species. In this report, the response of tobacco plants to BTH treatment is characterized and the fact that it controls disease by activating SAR is demonstrated. BTH does not cause an accumulation of salicylic acid (SA), an intermediate in the SAR signal transduction pathway. As BTH also induces disease resistance and gene expression in transgenic plants expressing the nahG gene, it appears to activate the SAR signal transduction pathway at the site of or downstream of SA accumulation. BTH, SA and TMV induce the PR-1a promoter using similar cis-acting elements and gene expression is blocked by cycloheximide treatment. Thus, BTH induces SAR based on all of the physiological and biochemical criteria that define SAR in tobacco.

Signal design for transmitter diversity wireless communication systems over Rayleigh fading channels

Abstract: Transmitter diversity wireless communication systems over Rayleigh fading channels using pilot symbol assisted modulation (PSAM) are studied. Unlike conventional transmitter diversity systems with PSAM that estimate the superimposed fading process, we are able to estimate each individual fading process corresponding to the multiple transmitters by using appropriately designed pilot symbol sequences. With such sequences, special coded modulation schemes can then be designed to access the diversity provided by the multiple transmitters without having to use an interleaver or expand the signal bandwidth. The code matrix notion is introduced for the coded modulation scheme, and its design criteria are also established. In addition to the reduction in receiver complexity, simulation results are compared to, and shown to be superior to, that of an intentional frequency offset system over a wide range of system parameters.

Vip3A, a novel Bacillus thuringiensis vegetative insecticidal protein with a wide spectrum of activities against lepidopteran insects.

Abstract: A novel vegetative insecticidal gene, vip3A(a), whose gene product shows activity against lepidopteran insect larvae including black cutworm (Agrotis ipsilon), fall armyworm (Spodoptera frugiperda), beet armyworm (Spodoptera exigua), tobacco budworm (Heliothis virescens), and corn earworm (Helicoverpa zea) has been isolated from Bacillus thuringiensis strain AB88. VIP3-insecticidal gene homologues have been detected in approximately 15% of Bacillus strains analyzed. The sequence of the vip3A(b) gene, a homologue of vip3A(a) isolated from B. thuringiensis strain AB424 is also reported. Vip3A(a) and (b) proteins confer upon Escherichia coli insecticidal activity against the lepidopteran insect larvae mentioned above. The sequence of the gene predicts a 791-amino acid (88.5 kDa) protein that contains no homology with known proteins. Vip3A insecticidal proteins are secreted without N-terminal processing. Unlike the B. thuringiensis 5-endotoxins, whose expression is restricted to sporulation, Vip3A insecticidal proteins are expressed in the vegetative stage of growth starting at mid-log phase as well as during sporulation. Vip3A represents a novel class of proteins insecticidal to lepidopteran insect larvae.

On the importance of peer influence for adolescent drug use: commonly neglected considerations

Abstract: Peer influence is generally believed to be a major cause of adolescent drug behavior. This paper reviews research findings on friend selection and projection to suggest that the magnitude of friend influence may be overestimated. This paper also observes that, although adolescent drug use is assumed to begin in response to peer group influence, peer groups have rarely been measured in studies of drug behavior. Social network analysis is identified as a promising method for measuring peer groups. The implications of this review for research and programs are considered.

Mucociliary differentiation of serially passaged normal human tracheobronchial epithelial cells.

Abstract: The goal of our studies was to establish procedures for subculturing normal human tracheobronchial epithelial (NHTBE) cells without compromising their ability to differentiate into mucous and ciliated cells (i.e., differentiation competence) and to study the regulation of airway secretions by epidermal growth factor (EGF) and retinoic acid (RA). Primary NHTBE cells were obtained from a commercial source and subcultured repeatedly in serum-free medium on plastic tissue culture dishes. The subcultured cells were tested after every passage for differentiation competence in air-liquid interface (ALI) cultures. The apical secretions of cultured NHTBE cells were characterized by immunoblotting, Western blotting, or enzyme-linked immunosorbent assay using a variety of antibodies. They contained mucin-like materials as well as lysozyme, lactoferrin, and secretory leukocyte protease inhibitor (SLPI). We found that an EGF concentration of 25 ng/ml, which is commonly used in airway cell cultures, adversely affected growth, mucin production, and morphology of ALI cultures and that RA was essential for mucociliary differentiation. Without RA, the epithelium became squamous and mucin secretions decreased 300- to 900-fold. In contrast, secretion of lysozyme, lactoferrin, and SLPI was significantly increased in RA-depleted cultures. Cells of passage 2 (P-2) through P-4 remained competent to differentiate into mucous and ciliated cells when grown in ALI cultures. However, mucin secretion and ciliagenesis decreased in P-3 and P-4 cell cultures and P-3 but not P-4 cell cultures exhibited bioelectric properties characteristic of airway epithelium. We concluded that P-2 and P-3 NHTBE cell cultures retain many important features of normal airway epithelium. This enables one to conduct many studies of airway cell biology with a greatly expanded (6,000-fold) cell pool.

Prevalence of psychiatric disorders among incarcerated women. II. Convicted felons entering prison

Abstract: Background: No unbiased estimates of the rates of psychiatric disorder among women prison inmates are available. Nonetheless, available data suggest that some psychiatric disorders are prevalent in this population. The objective of the study was to determine the rates, risk factors, and outcomes of specific psychiatric disorders among women prison inmates. Methods: A virtual census of women felons (N=805) entering prison in North Carolina was assessed using in-person interviews. Assessments were conducted for 8 disorders, using the Composite International Diagnostic Interview as the primary assessment measure. For validation purposes, one quarter of the inmates were reassessed for 2 of these disorders, using structured clinical interviews. Results: Inmates were found to have high rates of substance abuse and dependence and antisocial and borderline personality disorders compared with women in community epidemiologic studies. Rates among inmates were also somewhat elevated for mood disorders but not for anxiety disorders. The rate of reports of lifetime exposure to traumatic events was also high. Rates of disorder tended to be higher among white than among African American women. Conclusion: High rates of substance abuse, psychiatric disorder, and psychological distress associated with exposure to traumatic events suggest that women in prison have a need for treatment for substance abuse and other mental health problems.

Peptides from conserved regions of paramyxovirus fusion (F) proteins are potent inhibitors of viral fusion.

Abstract: The synthetic peptides DP-107 and DP-178 (T-20), derived from separate domains within the human immunodeficiency virus type 1 (HIV-1) transmembrane (TM) protein, gp4l, are stable and potent inhibitors of HIV-1 infection and fusion. Using a computer searching strategy (computerized antiviral searching technology, C.A.S.T.) based on the predicted secondary structure of DP-107 and DP-178 (T-20), we have identified conserved heptad repeat domains analogous to the DP-107 and DP-178 regions of HIV-1 gp41 within the glycoproteins of other fusogenic viruses. Here we report on antiviral peptides derived from three representative paramyxoviruses, respiratory syncytial virus (RSV), human parainfluenza virus type 3 (HPIV-3), and measles virus (MV). We screened crude preparations of synthetic 35-residue peptides, scanning the DP-178-like domains, in antiviral assays. Peptide preparations demonstrating antiviral activity were purified and tested for their ability to block syncytium formation. Representative DP-178-like peptides from each paramyxovirus blocked homologous virus-mediated syncytium formation and exhibited EC50 values in the range 0.015-0.250 microM. Moreover, these peptides were highly selective for the virus of origin. Identification of biologically active peptides derived from domains within paramyxovirus F1 proteins analogous to the DP-178 domain of HIV-1 gp4l is compelling evidence for equivalent structural and functional features between retroviral and paramyxoviral fusion proteins. These antiviral peptides provide a novel approach to the development of targeted therapies for paramyxovirus infections.

Chromosome aberrations, micronuclei, aneuploidy, sister chromatid exchanges, and cancer risk assessment.

Abstract: This paper describes the four cytogenetic endpoints most frequently used in hazard identification assays as the first step in the risk assessment process. These are structural chromosome aberrations, micronuclei, aneuploidy, and sister chromatid exchanges. The biological mechanisms involved in the formation of the alterations observed in each assay are briefly discussed. Variations in and recent improvements to each assay are described, with an emphasis on the use of molecular techniques to improve the sensitivity of the assay, and to allow for detection of specific alterations that are, or could be, associated with cancer induction. This, in turn, will make the data obtained in the cytogenetic assays more useful in cancer and genetic risk assessment. Thus, the aim of this paper is to encourage cytogeneticists to design their experiments in such a way that the data obtained will be of maximum possible benefit for characterizing and quantifying adverse human health effects, particularly cancer.

Glutathione S-transferase GSTT1 genotypes and susceptibility to cancer: studies of interactions with GSTM1 in lung, oral, gastric and colorectal cancers

Abstract: Allelism in glutathione S-transferase GSTM1 and GSTT1 has been suggested as a risk factor in various cancers. Accordingly, we describe a group of case-control studies carried out to identify associations between GSTT1 genotypes and susceptibility to lung, oral, gastric and colorectal cancers. The frequencies of the putatively high risk GSTT1 null genotype were not increased in the lung, oral or gastric cancer cases compared with controls but the frequency of this genotype was significantly increased (P = 0.0011, odds ratio = 1.88) in the colorectal cancer cases. No significant interactions between the GSTT1 and GSTM1 null genotypes were identified in the cancer groups studied. Indeed, no significant associations between GSTM1 genotypes and susceptibility were identified though further evidence was obtained that the protective effect of GSTM1*A and GSTM1*B is not equal. The data complement studies showing that GSTT1 null is associated with an increased susceptibility to total ulcerative colitis and suggests that this enzyme is important in the detoxification of unidentified xenobiotics in the large intestine.

Slicing object-oriented software

Abstract: Describes the construction of system dependence graphs for object-oriented software on which efficient slicing algorithms can be applied. We construct these system dependence graphs for individual classes, groups of interacting classes and complete object-oriented programs. For an incomplete system consisting of a single class or a number of interacting classes, we construct a procedure dependence graph that simulates all possible calls to public methods in the class. For a complete system, we construct a procedure dependence graph from the main program in the system. Using these system dependence graphs, we show how to compute slices for individual classes, groups of interacting classes and complete programs. One advantage of our approach is that the system dependence graphs can be constructed incrementally because representations of classes can be reused. Another advantage of our approach is that slices can be computed for incomplete object-oriented programs such as classes or class libraries. We present our results for C++, but our techniques can be applied to other statically typed object-oriented languages such as Ada-95.

Dual mode satellite/cellular terminal

Abstract: A method and apparatus of communicating information using Time Division Multiple Access and adaptive transmission and reception are disclosed. Signal bursts are transmitted from TDMA transmitters to a TDMA receiver wherein the transmitter codes the information and transmits coded information to the receiver using at least one of two timeslots of a plurality of timeslots in a repetitive TDMA frame period. Both of the two timeslots are received whether or not the transmitter has transmitted using one or two timeslots and the received signals are classified as intended and non-intended. Successively received signals classified as intended are then assembled into a block for decoding to reproduce the information.

Oxidant Generation and Lung Injury after Particulate Air Pollutant Exposure Increase with the Concentrations of Associated Metals

Abstract: We tested the hypothesis that particulate air pollutants are associated with metals that have a capacity to transport electrons and that biologic activity of the particulates can correlate with the concentrations of these metals. The metals studied were titanium, vanadium, chromium, manganese, iron, cobalt, nickel, and copper. Measurements included (1) oxidized products of deoxyribose catalyzed by particulates, (2) induction of a neutrophilic alveolitis after particulate instillation, (3) increments in airway reactivity after particulate instillation, and (4) mortality after exposures to both dusts and a microbial agent. Employing 10 different dusts of either natural or anthropogenic origin, in vitro generation of oxidized products of deoxyribose increased with ionizable concentrations of all metals, except for titanium, associated with the particles. After tracheal instillation of dust into rats, both the neutrophil influx and lavage protein increased with ionizable concentrations of these same m...