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Biomedical subjects

T Goldsmith

Publications and source records attributed to T Goldsmith.

6 recordsLinked to original sources

Characterization of asphalt fume composition under simulated road paving conditions by GC/MS and microflow LC/quadrupole time-of-flight MS.

A highly sensitive, selective, and reliable analytical method has been developed and validated for characterization of asphalt fume generated under simulated road paving conditions. A dynamic asphalt fume generation system was modified to provide consistent test atmospheres at simulated asphalt road paving conditions. In the process of fume generation, asphalt was initially preheated in an oven to 170 degrees C, pumped to a large kettle, which maintained the asphalt temperature between 150 and 170 degrees C, and then transferred to the generator. The fume was conducted from the generator to an exposure chamber through a heated transfer line. Characterization of the asphalt fume test atmospheres included the following: (1) determination of the consistency of the asphalt aerosol composition within the generation system; (2) quantification of total organic matter of the asphalt fume by electron impact ionization of isotope dilution gas chromatography/ mass spectrometry); and (3) identification of individual priority polycyclic aromatic hydrocarbons (PAHs) in asphalt fume by selected ion monitoring. With the developed method, asphalt fumes could be characterized into three fractions: (1) filter collection of a large molecular size fraction over a range of mass-to-charge (m/z) ratios of 173-309; (2) XAD-2 trapping of a medium molecular size fraction over a range of m/z ratios of 121-197; and (3) charcoal trapping of a small molecular size fraction that contained mainly the volatile vapor fraction over a range of m/z ratios of 57-141. Total organic matter of the asphalt fume was quantified over the 5 exposure days. Sixteen specific priority PAHs were monitored and identified. These PAHs were determined at trace levels on the filter fraction. A novel approach, which utilizes collision-induced dissociation of fragmentation pathway leading to a characteristic fragmentation pattern by coupling microflow liquid chromatography to atmospheric pressure chemical ionization of quadrupole time-of-flight mass spectrometry, was used to further clarify the trace amount of key components present in simulated road paving asphalt fumes. These results demonstrate that asphalt fume composition could be characterized and specific priority PAHs could be identified by this method. The major advantages of this method are its highly sensitivity, selectivity, and reliability for chemical hazard characterization in a complex mixture. This method is suitable for support toxicity studies using simulated occupational exposure to asphalt fumes.

Carcinogens, Environmental↗

PACT, a stress-modulated cellular activator of interferon-induced double-stranded RNA-activated protein kinase, PKR.

The interferon (IFN)-induced, double-stranded (ds)RNA-activated serine-threonine protein kinase, PKR, is a key mediator of the antiviral activities of IFNs. In addition, PKR activity is also involved in regulation of cell proliferation, apoptosis, and signal transduction. In virally infected cells, dsRNA has been shown to bind and activate PKR kinase function. Implication of PKR activity in normal cellular processes has invoked activators other than dsRNA because RNAs with perfectly duplexed regions of sufficient length that are able to activate PKR are absent in cellular RNAs. We have recently reported cloning of PACT, a novel protein activator of PKR. PACT heterodimerizes with PKR and activates it by direct protein-protein interaction. Overexpression of PACT in mammalian cells leads to phosphorylation of the alpha subunit of the eukaryotic initiation factor 2 (eIF2alpha), the cellular substrate for PKR, and leads to inhibition of protein synthesis. Here, we present evidence that endogenous PACT acts as a protein activator of PKR in response to diverse stress signals such as serum starvation, and peroxide or arsenite treatment. Following exposure of cells to these stress agents, PACT is phosphorylated and associates with PKR with increased affinity. PACT-mediated activation of PKR leads to enhanced eIF2alpha phosphorylation followed by apoptosis. Based on the results presented here, we propose that PACT is a novel stress-modulated physiological activator of PKR.

3T3 Cells↗

Use of the radial forearm fasciocutaneous free flap and montgomery salivary bypass tube for pharyngoesophageal reconstruction.

BACKGROUND: Head and neck reconstructive surgeons involved in pharyngoesophageal reconstruction have several options available to repair the defect after partial or total laryngopharyngectomy. There is no uniform agreement among head and neck surgeons as to which of the most frequently used techniques offers the best results. METHODS: A retrospective study was performed on 20 consecutive patients who had undergone reconstruction of the hypopharynx and cervical esophagus using a radial forearm free flap with Montgomery salivary bypass tube at the Massachusetts Eye and Ear Infirmary in Boston, Massachusetts, and St. Louis University, Department of Otolaryngology-Head and Neck Surgery between 1992 and 1996. This reconstruction was used for primary reconstruction after total or partial laryngopharyngectomy with cervical esophagectomy, partial pharyngectomy sparing the larynx, and for reconstruction of the stenotic neopharynx after laryngectomy. RESULTS: The overall rate of pharyngocutaneous fistula was 20%, and the rate of postoperative stricture was 10%. Of patients reconstructed with this technique, 85% were able to resume oral alimentation, whereas 15% remained G-tube dependent. Of the 18 patients who did not have their larynges remain intact, 6 were able to develop useful tracheoesophageal speech. CONCLUSIONS: The results of this study show that the radial forearm fasciocutaneous free flap in combination with the Montgomery salivary bypass tube is extremely useful for reconstruction of partial and circumferential defects of the hypopharynx and cervical esophagus.

Adult↗

Acute inflammatory reaction in rats after intratracheal instillation of material collected from a nylon flocking plant.

Several cases of interstitial lung disease have been diagnosed among workers at a nylon flock plant, but the etiologic agent for the disease outbreak was unknown. The results of a medical survey and industrial hygiene study indicated that the dust present in the plant may be responsible. Thus, airborne dust collected at the plant was examined for its inflammatory potential in rat lungs. The endpoints measured were: (1) breathing rates, (2) differential cell counts of bronchoalveolar lavage cells, (3) alveolar macrophage (AM) chemiluminescence, (4) albumin concentration and matrix metalloprotease activities in the acellular fluid from the initial bronchoalveolar lavage, and (5) pulmonary histopathology. In the first study, rats received a single dose of the airborne dust sample (10 mg/kg body weight) by intratracheal (IT) instillation. At 1 d post-IT, all inflammatory endpoints were significantly increased versus controls, but by 29 d post-IT they did not differ significantly from controls. Histopathology demonstrated mild to moderate, multifocal, suppurative pneumonia, usually centered around bronchioles, at 1 d post-IT. At 29 d post-IT, pulmonary inflammation was minimal to mild and characterized by alveolar histocytosis usually restricted to the immediate area of retained bire-fringent fibers. In subsequent experiments, airborne dust was extracted with water and the dust (washed airborne dust) and water extract (soluble fraction) were separated by centrifugation for further study. Nylon tow dust was prepared in the laboratory by milling uncut nylon strands (called tow) that had not been treated with the finish or dyes that are commonly used in the flock plants. Rats were administered a single dose of a dust sample (10 mg/kg body weight) or the soluble fraction (1.3 ml/kg body weight) by IT administration and the same endpoints were measured at 1 d post-IT. The dust samples caused significant increases in all of the inflammatory endpoints; however, the soluble fraction was much less active. Histological analysis of the lungs 1 d post-IT confirmed lung inflammation was occurring and tended to center around bronchioles. The results suggest that: (1) nylon flocking generates particles of respirable size that can interact with AM in the lung and can be detected in the lung 29 d after exposure, (2) the dust samples examined cause an inflammatory response, (3) water-extractable agent(s) from airborne dust contribute only minimally to the inflammatory response, and (4) the acute inflammatory response to these dusts is substantial when compared to other pathologic occupational dusts previously examined in our laboratory.

Acute Disease↗