Showing papers by "Research Triangle Park published in 1984"
TL;DR: This review of the literature is intended as an evaluative report rather than an annotated bibliography of all the source material examined on hydrogen sulfide, noting information gaps that may require further investigation.
Abstract: The information available on the biological activity of hydrogen sulfide has been examined for present status of critical results pertaining to the toxicity of hydrogen sulfide. This review of the literature is intended as an evaluative report rather than an annotated bibliography of all the source material examined on hydrogen sulfide. The information was selected as it might relate to potential toxic effects of hydrogen sulfide to man and summarized, noting information gaps that may require further investigation. Several recommendations are listed for possible consideration for either toxicological research or additional short- and long-term tests. Two bibliographies have been provided to assist in locating references considered in this report: (1) literature examined but not cited and (2) reference citations. The majority of the references in the first bibliography were considered peripheral information and less appropriate for inclusion in this report.
909 citations
TL;DR: Findings give additional support to the potential value of the RD50 model for setting occupational exposure guidelines and predicting the risk of injury to the respiratory tract from exposure to airborne sensory irritants.
195 citations
TL;DR: It is shown that chronic administration of low-modest doses of tricyclic antidepressants frequently cause considerable weight gain and can significantly interfere with the ability to provide long-term maintenance therapy.
165 citations
Patent•
15 Aug 1984TL;DR: A composition for use in an aqueous environment which comprises a formulation containing a water-soluble pharmaceutically beneficial agent, a waterinsoluble, water-permeable film coating surrounding the formulation, and particulate, watersoluble, pore-forming material dispersed within the film coating is presented in this paper.
Abstract: A composition for use in an aqueous environment which comprise a formulation containing a water-soluble pharmaceutically beneficial agent, a water-insoluble, water-permeable film coating surrounding the formulation, and particulate, water-soluble, pore-forming material dispersed within the film coating.
148 citations
TL;DR: Research revealed pronounced differences in the activity of the DNT isomers and provided the reason for the dissimilar results of the various carcinogenicity studies and provided valuable information in establishing the risk of these compounds to humans.
Abstract: (1984). Dinitrotoluene: Acute Toxicity, Oncogenicity, Genotoxicity, and Metabolism. CRC Critical Reviews in Toxicology: Vol. 13, No. 3, pp. 217-234.
138 citations
TL;DR: A nonlinear increase in covalent binding to respiratory mucosal DNA with increasing CH2O concentrations may be explained by a decrease in the efficiency of defense mechanisms or by an increase in the availability of reaction sites on the DNA resulting from increased cell turnover.
130 citations
TL;DR: Fischer 344 rats were exposed to 100, 33, 10, or 0 ppm of ethylene oxide vapor (EtO) by inhalation for 6 hr per day, 5 days per week, for approximately 2 years as mentioned in this paper.
128 citations
TL;DR: This work investigated whether a protein, α-amylase, one of several hydrolytic enzymes secreted from the aleurone of wheat into the endosperm during germination, could be processed and secreted in an active form from the yeast Saccharomyces cerevisiae, secretion being dependent upon the plant signal sequence.
Abstract: The translocation of secretory proteins across the endoplasmic reticulum involves the recognition and cleavage of an amino-terminal extension called the signal sequence1. The structure of signal peptides appears to be ubiquitous in having a very hydrophobic central core2, so that the signal sequence in secretory proteins from one organism could possibly be recognized by the processing and transport apparatus of another. We therefore wished to investigate whether a protein, α-amylase, one of several hydrolytic enzymes secreted from the aleurone of wheat into the endosperm during germination, could be processed and secreted in an active form from the yeast Saccharomyces cerevisiae, secretion being dependent upon the plant signal sequence. Here, synthesis of α-amylase was by inserting a cDNA clone coding for the entire α-amylase structural gene3 into a yeast expression vector4. The α-amylase protein coded for by this gene fusion has the signal sequence located internally, not at the N-terminal end of the polypeptide. Nevertheless, it is processed and the processed form is secreted into the medium in an active form. There are potential industrial applications for yeast that secrete a functional α-amylase.
120 citations
TL;DR: Findings suggest that murine stock and strain-dependent differences in sensitivity to two-stage skin carcinogenesis may not be due to major differences in the metabolism of the initiating hydrocarbons, but are partially the consequences of the agents used for promotion.
Abstract: Several approaches were employed to investigate whether murine stock and strain differences in susceptibility to two-stage skin carcinogenesis are due to differences in the metabolism of the initiating aromatic hydrocarbons, or the consequences of the agents used for promotion. A cell-mediated mutagenesis assay was used to quantitatively compare the abilities of cultured newborn SENCAR, DBA/2, C57BL/6 and BALB/c keratinocytes to metabolize dimethylbenz[a]anthracene (DMBA) to mutagenic and cytotoxic metabolites. At equivalent concentrations of DMBA, throughout a 25-fold range in promutagen concentration, C57BL/6, BALB/c and SENCAR keratinocyte-dependent mutant frequencies were very similar and approximately twice DBA/2 keratinocyte-dependent mutant frequencies. In in vivo tumor studies, C57BL/6 mice were more sensitive than SENCAR mice to complete skin carcinogenesis protocols employing repetitive weekly treatments with DMBA and benzo[a]pyrene (BP). At equivalent concentrations of either DMBA or BP, C57BL/6 mice developed carcinomas sooner, and had a greater number of carcinomas per animal. SENCAR mice were very sensitive to two-stage skin carcinogenesis protocols employing BP and DMBA as initiators and benzoyl peroxide and 12-O-tetradecanoylphorbol-13-acetate (TPA) as promoters. C57BL/6 mice were relatively refractory to TPA promotion but sensitive to promotion with benzoyl peroxide. These findings suggest that murine stock and strain-dependent differences in sensitivity to two-stage skin carcinogenesis may not be due to major differences in the metabolism of the initiating hydrocarbons, but are partially the consequences of the agents used for promotion.
112 citations
TL;DR: Several chemicals were highly correlated with each other in personal air samples, indicating possible common sources of exposure and some, but not all, of the potentially occupationally exposed individuals had significantly higher workplace exposures to several chemicals.
110 citations
TL;DR: The data indicate that the rat nasal mucosa, which is the major target site for both aldehydes in inhalation toxicity studies, can metabolize both formaldehyde and acetaldehyde, and that the specific activities of formalde and aldehyde dehydrogenase in homogenates of the nasal mucoso are essentially unchanged following repeated exposures to toxic concentrations of either compound.
TL;DR: Levels of GTP cyclohydrolase, neopterin and biopterin were determined in tissues and body fluids of humans, monkey, dog and mouse, while none could be detected in mouse, rat, guinea pig or hamster urine.
TL;DR: The nopaline synthase-β-galactosidase fusion described in this paper was constructed using the unique BamHI site of the nopalin synthase gene to construct an in-frame fusion, pGHlac+.
Abstract: A New Chimeric Gene as a Marker for Plant Transformation: The Expression of Escherichia coli β-Galactosidase in Sunflower and Tobacco Cells
TL;DR: It is suggested that the evaluation of hormonal influences on operant behaviors sensitive to tranquilizers should be a useful model system for studying possible mechanisms underlying emotional changes associated with reproductive cycles.
TL;DR: It is concluded that the present results are consistent with the existence of three receptor sub-types; however, it is suggested that substance P is the natural agonist for only one of these receptors, and that substance K and tuftsin may be the transmitters for the other two receptorSub-types.
TL;DR: DMBA, a more potent carcinogen than B[a]P, produces a more extensive B-cell suppression than B(a)P as well as alters host resistance to tumor and bacterial challenge.
TL;DR: Curve-linear regression analyses for the dose responsiveness of these parameters demonstrated that serum testosterone concentration initially decreased at a rate of 19%/mumol Cd/kg, respectively, and was the most sensitive to Cd exposure.
TL;DR: The sensory irritation potential of a series of saturated and unsaturated aliphatic and cyclic aldehydes was investigated in B6C3F1 and Swiss-Webster mice and tentative threshold limit values (TLVs), based upon prevention of sensory irritation, were extrapolated from the RD50 values of Swiss- Webster mice.
TL;DR: The findings indicate the complexity of cell types composing the rat nasal respiratory epithelium, with goblet cells, basal cells, ciliated cells, nonciliated columnar cells, cuboidal cells, and brush cells having distinct ultrastructural features.
Abstract: This ultrastructural study of the respiratory epithelium of the rat nasal mucosa revealed six morphologically distinct cell types: goblet cells, basal cells, ciliated cells, nonciliated columnar cells, cuboidal cells, and brush cells. The latter three have not been previously characterized in the rat nasal mucosa by transmission electron microscopy. Cuboidal cells observed on the conchae and lateral wall had short apical microvilli which were less dense than the microvilli of the nonciliated columnar cells. Nonciliated columnar cells also identified on the conchae and lateral wall had short microvilli and an extensive network of smooth endoplasmic reticulum in the apical region. The brush cell had distinct ultrastructural features; it was pear-shaped, with the broad base adjacent to the basement membrane and large microvilli on the surface. Microfilaments, microtubules, vesicles, and paired cisternae were found in the apical cytoplasm. Brush cells occurred singly on the conchae and lateral wall but were not identified in the respiratory epithelium of the nasal septum. These findings indicate the complexity of cell types composing the rat nasal respiratory epithelium.
TL;DR: The results indicate that NiCl2 predominantly affects T-cell mediated immune responses and natural killer cells.
TL;DR: Oxymetazoline demonstrated a pronounced organ selectivity, when compared to noradrenaline, by being a potent full agonist in rat anococcygeus muscle and a partial agonists in rat vas deferens, and theoretical modelling and experimental results indicate that high affinity/low efficacy agonists are much more sensitive to receptor coupling.
Abstract: Oxymetazoline demonstrated a pronounced organ selectivity, when compared to noradrenaline, by being a potent full agonist in rat anococcygeus muscle and a partial agonist in rat vas deferens. Responses of rat anococcygeus muscles to oxymetazoline were relatively more sensitive to antagonism by phenoxybenzamine (Pbz) an alkylating alpha-adrenoceptor antagonist. Therefore, although oxymetazoline was more potent than noradrenaline in this tissue, after Pbz (0.3 microM for 10 min), the responses to oxymetazoline were completely inhibited while those to noradrenaline were only partially inhibited. Schild analysis with phentolamine, corynanthine, prazosin and yohimbine indicated no alpha-adrenoceptor heterogeneity within the rat anococcygeus muscle or between this tissue and rat vas deferens. Measurement of agonist Kd values and Schild analysis of oxymetazoline antagonism of responses to noradrenaline (after alkylation) confirmed the homogeneity of alpha-adrenoceptors with respect to these two agonists. The above profiles of activity would be predicted if oxymetazoline had a higher affinity but lower efficacy than noradrenaline. Experimentally this was confirmed when it was found that oxymetazoline had 5 times the affinity but 0.2 to 0.3 times the efficacy of noradrenaline. These results serve as a caveat to the use of selective receptor desensitization and/or selective receptor alkylation (or protection from alkylation) as means of differentiating drug receptors. Theoretical modelling and these experimental results indicate that high affinity/low efficacy agonists are much more sensitive to receptor coupling. The implications for therapeutic selectivity could be important in that high affinity/low efficacy agonists theoretically have a much greater potential for organ selectivity.
TL;DR: Analysis of the fluid collected at the rete testis indicated that there was no treatment-related change in the relative amounts of androgen binding protein, indicating that the spermatocyte is the primary target cell for the histologic effects of EGME in the testis of F344 rats.
Abstract: Ethylene glycol monomethyl ether (EGME) has been found to produce testicular atrophy in experimental rodents. The studies that follow were designed to determine the testicular cell type(s) most susceptible to EGME administration. For histologic studies, F344 rats were gavaged with 150 mg/kg/day of EGME 5 days per week, and serially sacrificed. In sections from perfusion-fixed tissue, necrotic changes were observed in some meiotic and premeiotic spermatocytes 24 hours after a single dose. Also, nuclear condensation was seen in occasional early pachytene spermatocytes. These effects were magnified after two doses; there were more necrotic pachytene and meiotic spermatocytes than necrotic stage I pachytene spermatocytes. By day 4, testes from all treated animals were affected; there was a pronounced maturation-depletion effect, seen as the absence of round spermatids from tubules in stages I to III. These effects continued to develop at days 7 and 10, leaving only Sertoli cells, spermatogonia, and late stage spermatids populating the epithelium. Other animals were treated similarly, but subject to efferent duct ligation 16 hours prior to sacrifice. Fluid production, as judged by weight gain in the testes after efferent duct ligation, was unaffected by EGME treatment. Analysis of the fluid collected at the rete testis indicated that there was no treatment-related change in the relative amounts of androgen binding protein. The data indicate that the spermatocyte is the primary target cell for the histologic effects of EGME in the testis of F344 rats.
TL;DR: Observative TPN teams do not necessarily ensure optimum TPN therapy and institutions using this approach to provide nutrition parenterally must be prepared to establish the incidence of TPN-related complications and to expand the involvement of the TPN team as required to control the frequency of these anomalies.
Abstract: A two part, prospective study was undertaken to establish the existing frequency of total parenteral nutrition-(TPN) related mechanical, metabolic, and septic complications in an institution with a consultative TPN team (group A) and to determine if increasing the involvement of the TPN team in patient monitoring and verifying adherence to TPN infection control guidelines would reduce the incidence of these complications (group B). The initial 28 consecutive patients were managed entirely by their primary physicians with the role of the TPN team limited to consultative activities while the next 29 patients receiving TPN were managed jointly by their primary physicians and the TPN team. Analysis of the results show group B to have a significant reduction in metabolic complications, decreased incidence of mechanical abnormalities, and approximately equal incidences of documented sepsis. However, when compared to the results of an institution in which the TPN team has complete control of TPN therapy, even the group B patients had a relatively excessive number of TPN-related complications especially in the categories of mechanical and metabolic abnormalities. Thus, consultative TPN teams do not necessarily ensure optimum TPN therapy and institutions using this approach to provide nutrition parenterally must be prepared to establish the incidence of TPN-related complications and to expand the involvement of the TPN team as required to control the frequency of these anomalies.
Patent•
20 Nov 1984TL;DR: In this article, the topical use of nicotinamide to promote angiogenesis, reepithelialization and wound healing is discussed, and a vehicle for administering it is proposed.
Abstract: This invention pertains to the topical use of nicotinamide to promote, angiogenesis, reepithelialization and wound healing. Formulations and vehicles for administering nicotinamide are also within the scope of this invention.
TL;DR: Comparisons were made of the effects of cismethrin and deltamethrin exposure on motor activity and the acoustic startle response in male Long-Evans rats to better characterize the behavioral toxicity of pyrethroid insecticides.
TL;DR: Levels of urinary neopterin and biopterin were determined in patients having a diagnosis of schizophrenia, unipolar depression, or bipolar depression and subclassification of patients into primary and secondary depression demonstrated a significant elevation of urinaryBiopterin in both groups, whereas urinary Neopterin was elevated only in those patients with primary depression.
Abstract: Levels of urinary neopterin and biopterin were determined in patients having a diagnosis of schizophrenia, unipolar depression, or bipolar depression. Both neopterin and biopterin levels were significantly higher in the urine of patients with unipolar depression than in the urine of the control group. Subclassification of patients into primary and secondary depression demonstrated a significant elevation of urinary biopterin in both groups, whereas urinary neopterin was elevated only in those patients with primary depression. In patients with bipolar depression, neopterin excretion was elevated, but biopterin excretion did not differ from controls. No significant differences were found in schizophrenic patients.
TL;DR: It was concluded that the initial testicular effects of MeCl are directed at either the late stage spermatids or the Sertoli cells with a resultant delay in spermiation.
TL;DR: Protein kinase C has been purified by a rapid method resulting in a high-yield, stable enzyme preparation and the catalytic and regulatory properties were characterized employing histone H1 and HMG8, a proteolytic fragment of H1.
TL;DR: In this paper, the authors evaluated the relationship between surface area and reaction rate and found that the rate of CaS formation increases exponentially with the specific surface area of CaO in micrometer size particles and that the effect of surface area on reactivity is at least as great as that expected for pure diffusion control.
Abstract: Details are presneted of a new limestone injection multistage burner as an economical and practical method of reducing emissions from existing power plants by 50%. The process involves injection of pulverized limestone into coal burners that are designed to minimize NO/sub x/ formation by staged combustion. The reaction of CaO with SO/sub 2/ following combustion is the principal mechanism of sulfur capture in the LIMB process. The relationship between surface area and reaction rate is evaluated. It was found that the rate of CaS formation increases exponentially with the specific surface area of CaO in micrometer size particles. The effect of surface area on reactivity is at least as great as that expected for pure diffusion control. The activation energy of CaO reaction with H/sub 2/S or COS is 31 kcal/mol for the limestone studied. On the basis of the activation energy measured between 600/sup 0/ and 900/sup 0/C, and the reaction rates measured for CaO of 40 m/sup 2//g surface area, efficient sulfur capture would be predicted at 1250/sup 0/C in a dispersed-particle system if the kinetics of CaS formation is the only limitation.
TL;DR: 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) has been detected at levels ranging from 20 to 173 parts per trillion in adipose tissue from three Vietnam veterans who were "heavily exposed to Herbicide Orange".