PubMed Health⌕ Search

Biomedical subjects

N F Johnson

Publications and source records attributed to N F Johnson.

At least 37 records · Page 2Linked to original sources
PubMed1994

Phagosomal pH and glass fiber dissolution in cultured nasal epithelial cells and alveolar macrophages: a preliminary study.

The dissolution rate of glass fibers has been shown to be pH sensitive using in vitro lung fluid simulant models. The current study investigated whether there is a difference in phagosomal pH (ppH) between rat alveolar macrophages (AM) and rat nasal epithelial cells (RNEC) and whether such a difference would influence the dissolution of glass fibers. The ppH was measured in cultured AM and RNEC using flow cytometric, fluorescence-emission rationing techniques with fluorescein-labeled, amorphous silica particles. Glass fiber dissolution was determined in AM and RNEC cultured for 3 weeks with fast dissolving glass fibers (GF-A) or slow dissolving ones (GF-B). The mean diameters of GF-A were 2.7 microns and of GF-B, 2.6 microns, the average length of both fibers was approximately 22 to 25 microns. Dissolution was monitored by measuring the length and diameter of intracellular fibers and estimating the volume, assuming a cylindrical morphology. The ppH of AM was 5.2 to 5.8, and the ppH of RNEC was 7.0 to 7.5. The GF-A dissolved more slowly in RNEC than in AM, and no dissolution was evident in either cell type with GF-B. The volume loss with GF-A after a 3-week culture with AM was 66% compared to 45% for cultured RNEC. These results are different from those obtained using in vitro lung fluid-simulant models where dissolution is faster at higher pH. This difference suggests that dissolution rates of glass fibers in AM should not be applied to the dissolution of fibers in epithelial cells.

Animals↗
PubMed1994

On the naming of color words and color patches.

Subjects can name color words faster than they can name color patches. To account for that effect, a generic model of naming is described which assumes that words access the mental lexicon directly, whereas color patches do so only indirectly via an initial imaginal or semantic representation. However, Lund (1927) reported that the naming advantage for words disappeared when all the items to be named on a page were the same (i.e., they were blocked). In the present study, three experiments are reported that were designed to provide a clearer empirical definition of Lund's blocking effect and to ascertain the extent to which it requires a modification of the generic model. The blocked lists had 50 items arranged into 10 blocks, with each block homogeneous with respect to color. The block lengths were either all a predictable length of 5 items or they varied randomly from 1 to 9 items. The data indicated the following: (1) The blocking effect occurred even when the task required a full identification of each item, and (2) the blocking effect was confined to within-block transitions. Blocking seemed to eliminate the word advantage by allowing the subject to re-use the lexical entry used for the immediately prior items, which is consistent with the generic model.

Color Perception↗
PubMed1994

An overview of animal models for assessing synthetic vitreous fibers (SVFs) safety.

Synthetic vitreous fibers (SVFs) are materials with many important commercial applications. The fibrous nature of the SVFs raises concerns about their potential human health hazards. However, sufficient epidemiological data do not exist to establish the hazardous nature of all SVFs. In addition, the cellular and molecular mechanisms underlying the induction of pulmonary lesions are only partially understood. Without sufficient evidence to associate fiber exposure and lung disease, animal bioassays have been used to identify specific hazardous fibers. These bioassays include inhalation exposures, intratracheal instillation, and intracavitary injection (intrapleural and intraperitoneal). Inhalation exposures of animals most closely represent the human experience, but these exposures are costly and time-consuming to conduct. Intratracheal and intracavitary administrations of fiber are alternatives to inhalation exposures; however, they do not represent human exposures and can give false positive results. The limitations of the noninhalation approaches must be considered when addressing the potential for a respirable fiber to induce human lung disease. In addition, when the results from inhalation exposures do not agree with the alternative animal assays, most weight should be given to the animal inhalation assays because of the limitations of the alternative approaches. To determine the safety of SVFs, both the inhalation and noninhalation approaches are suggested.

Air Pollutants, Occupational↗
PubMed1994

Estimation of the dose of radon progeny to the peripheral lung and the effect of exposure to radon progeny on the alveolar macrophage.

Groups of rats were exposed to radon progeny attached to a vector aerosol of cigarette smoke particles in a closed-loop exposure system. The total exposures ranged from 70 to 1020 WLM over a 3-5-h period. Alveolar macrophages were lavaged from exposed and control rats (exposed to the vector aerosol alone). There were no differences between phagocytic capabilities of the macrophages lavaged from the controls and any group of exposed rats. The increases in the numbers of binucleated/multinucleated and micronucleated macrophages were enumerated using cytological preparations of lavaged alveolar macrophages after exposure compared to the numbers in the control rats. The peak response in numbers of binucleated/multinucleated and micronucleated macrophages occurred at 21 days after exposure, beyond which the numbers decreased. This peak response showed a significant exposure-dependent relationship. The number of micronuclei provided a sensitive indicator of exposure. The lowest exposure level used (70 WLM) resulted in a significant difference in the number of micronucleated macrophages between control and exposed rats. The alpha-particle dose to the peripheral lung was estimated by comparing formation of micronuclei in cultured macrophages exposed to alpha particles from 238Pu (where the dose was known) to micronuclei in lavaged macrophages from animals exposed to radon progeny (where the exposure concentration was known, but the dose was not known). The dose estimated in this way for the peripheral lung was 9.8 +/- 1.2 mGy/WLM. This value is three to five times higher than predicted from mathematical models currently available.

Animals↗
PubMed1993

The effect of semantic priming on the detection of letters within words.

Smith (1979) reported an experiment in which subjects were to detect whether or not a displayed word contained a particular target letter. Her data indicated that if the word bearing the target letter was preceded by a semantically related item, the detection of the target letter was faster than it was if the preceding item was unrelated. Those results provided strong support for holistic models of word recognition, in which it is assumed that letter detection must be mediated by prior word recognition. That is, any facilitating effect of the prime on lexical access should be passed on to subsequent letter detection. The present experimental paradigm, which was very similar to (albeit different from) that of Smith, served to explore the generality of her effect, but the results did not confirm her findings. Although a lexical-decision task used in Experiments 2, 5, and 7 provided clear evidence that the priming items employed in these experiments did facilitate lexical processing, a letter-detection task used in Experiments 1, 3, 4, 6, and 8 failed to reveal any facilitating effect of semantic priming on letter detection. The conclusion is that the generality of Smith's effect is far too limited to offer support for holistic models of word recognition.

Adult↗
PubMed1992

In vitro activity of silicon carbide whiskers in comparison to other industrial fibers using four cell culture systems.

Silicon carbide whiskers (SiCW) and continuous glass filaments are important components of composite materials having potentially widespread use in the automotive, aerospace, and power generation industries. We determined the in vitro activity of three well-characterized samples of silicon carbide whiskers and a continuous glass filament sample in four different cellular assays and compared this to the activities of UICC crocidolite, JM Code 100 glass microfiber, and erionite in the same assay systems. The SiCW had a diameter range of 0.32-0.75 microns and a length range of 4.5-20.1 microns. The SiCW was significantly toxic; on a mass basis, one SiCW sample was more toxic than crocidolite; however, JM Code 100 glass microfiber, which is not toxic in vivo (i.e., it does not cause fibrogenesis or carcinogenesis when inhaled), was also more toxic than crocidolite. The glass filament sample was the least cytotoxic of all the samples tested. On a fiber number basis, all three SiCW samples were more toxic than crocidolite. The results of our study showed that SiCW exhibits significant in vitro biological reactivity. Thus, despite the caution that must be exercised in extrpolating the results of in vitro studies to conclusions about in vivo health effects, SiCW should be considered toxic until further toxicological data are available.

Aluminum Silicates↗
PubMed1992

Fiber-induced hydroxyl radical formation: correlation with mesothelioma induction in rats and humans.

As part of a program to study the effects of inhaled fibers, we characterized the capacity of various fibers to initiate hydroxyl radical (.OH) formation from hydrogen peroxide in a non-cellular system. We studied five natural fibers (erionite, crocidolite, amosite, anthophyllite and chrysotile) and two man-made fibers (JM code 100 glass fibers and glass wool). The fibers were incubated for 5 min at 37 degrees C with hydrogen peroxide and salicylic acid in pH 7.0 aqueous solutions. The salicylate reacted with any .OH formed in these mixtures to produce stable addition products. The amount of .OH addition products formed during the incubations was determined by the salicylate assay which uses HPLC with electrochemical detection. Erionite, JM code 100 and glass wool were the most effective initiators of .OH formation, followed, in order, by crocidolite, amosite and chrysotile. When the capacity of the natural fibers to initiate .OH formation was plotted versus either the values for tumor rates of rats that received pleural inoculations of fibers or the literature values for the human mesothelioma mortality rates, positive correlations (r2 > or = 0.896) were found. Similar correlations with man-made fibers were not found. No positive correlation could be made between .OH formation capacity versus the tumor rates of rats that received peritoneal injections of either type of fibers.

Aluminum Silicates↗
PubMed1992

The utility of animal inhalation studies to assess the risk of mineral fiber-induced pulmonary cancer.

Animal inhalation exposures to fibrous materials such as crocidolite and erionite produce lesions similar to those found in exposed humans. This indicates that the animal inhalation model is relevant for identifying hazardous fibrous materials. Intratracheal instillations and intracoelomic injections are alternative bioassays that can be used to screen for the most biologically active materials. These nonphysiological routes of administration can give false positive results; therefore, animal inhalation studies should be the ultimate bioassay used in the absence of appropriate epidemiological data.

Animals↗
PubMed1991

Carcinogenicity of the insulation wools: reassessment of the IARC evaluation.

In assessing the health evidence concerning man-made mineral fibers, the chemical composition, surface activity, durability, and size of fibers have to be taken into account. Special-purpose fine glass fibers need to be separated from the insulation wools (glass, rock, and slag wool). The epidemiological evidence is sufficient to conclude that there has been no mesothelioma risk to workers producing or using glass wool, rock wool, or slag wool. The epidemiological studies have been large and powerful, and they show no evidence of a cause-effect relationship between lung cancer and exposure to glass wool, rock wool, or slag wool fibers. There is some evidence of a small cancer hazard attached to the manufacturing process in slag wool plants 20 to 50 years ago, when asbestos was used in some products and other carcinogenic substances were present. However, this hazard is not associated with any index of exposure to slag wool itself. Animal inhalation studies of ordinary insulation wools also show that there is no evidence of hazard associated with exposure to these relatively coarse, soluble fibers. The evidence of carcinogenicity is limited to experiments with special-purpose fine durable glass fibers or experimental fibers, and only when these fibers are injected directly into the pleural or peritoneal cavity. Multiple chronic inhalation studies of these same special-purpose fine glass fibers have not produced evidence of carcinogenicity. It is suggested that the present IARC evaluation of the carcinogenic risk of insulation wools should be revised to Category 3: not classifiable as to carcinogenicity to humans.

Animals↗
PubMed1990

Proliferative responses of rat nasal epithelia to ozone.

The epithelium of the female Fischer 344/N rat anterior nasal cavity was examined and found to be composed of four types of epithelia: squamous, ciliated respiratory, nonciliated cuboidal/transitional, and olfactory. DNA replication in these tissues was monitored by bromodeoxyuridine (BrdUrd) incorporation. Labeled cells were identified using a monoclonal antibody recognizing BrdUrd. Ciliated respiratory, nonciliated cuboidal/transitional, and olfactory epithelia from control animals had a low level of DNA replication (1 labeled cell/mm basal lamina); in contrast, the squamous epithelium contained 40 labeled cells per millimeter basal lamina. Female Fischer 344/N rats were exposed to 0.0, 0.12, 0.27, or 0.8 ppm ozone, 6 hr/day for up to 7 days. Observations were made after 3 or 7 days of exposure and after 3 or 7 days of recovery from the 7-day exposure. Following exposure to 0.8 ppm ozone, a transient but marked increase in DNA replication was seen in the nonciliated cuboidal/transitional, while in ciliated respiratory and olfactory epithelia the transient increase in DNA replication was less marked. This increase was prominent after 3 days of exposure and absent by 7 days of exposure in all but the cuboidal/transitional epithelium. Exposure to 0.8 ppm ozone for either 3 or 7 days resulted in hyperplasia of the cuboidal epithelium. A depressed level of DNA replication was seen in the squamous epithelium following 7 days of recovery from 7 days of ozone exposure to 0.8 ppm ozone. This study shows that there are regional differences in DNA replication within the anterior nasal epithelium of the rat and that these levels are modulated by exposure to irritants. The cuboidal/transitional epithelium was the most responsive epithelial cell type to the effects of ozone exposure and may, therefore, provide a sensitive indicator of irritant damage to the respiratory tract.

Animals↗
PubMed1990

Separation and characterization of basal and secretory cells from the rat trachea by flow cytometry.

Basal and secretory cells have been separated as highly enriched viable populations from single-cell suspensions of rat tracheal epithelial cells. Isolation of the populations was achieved by preparation of a cell suspension and separation by flow cytometry using contour maps generated from 2 degrees and 90 degrees light scatter signals. Flow cytometric analysis of cells showed 10% of the whole preparation were cells in SG2M phase of the cell cycle. The secretory cells accounted for 86% of these cycling cells; the remainder were accounted for by the basal cells. Culture of sorted populations of basal and secretory cells in serum free defined medium showed that basal cells had a lower (0.6%) colony-forming efficiency than secretory cells (3.4%). Significant differences in blue auto-fluorescence, Hoechst 33342 uptake, and lectin staining were apparent between basal and secretory cells. These results suggest that the secretory cell rather than the basal cell is primarily the cell type involved in maintenance of the normal tracheal epithelium. Secretory cells are greater in number, have a higher proliferative potential, and greater metabolic capability. Because of these traits they may be a critical cell at risk from damage by environmental agents.

Animals↗
PubMed1990

DNA adduct formation in rat alveolar type II cells: cells potentially at risk for inhaled diesel exhaust.

Diesel exhaust (DE) is a pulmonary carcinogen in rats. One potential mechanism for DE-induced carcinogenicity involves the interaction of the organic chemicals associated with DE soot with DNA in target cells. The purpose of this study was to determine whether peripheral lung cells, specifically alveolar type II cells, are at risk from inhaled DE. Rats were exposed 16 hr/day, 5 days/week to filtered air (controls), carbon black (CB) (6.2 mg/m3), or to diluted DE (6.2 mg/m3) for 12 weeks. CB particles were used for comparison with DE soot, because the CB particles are morphologically similar to soot particles, but are virtually devoid of adsorbed organic compounds. Type II alveolar cells were isolated by flow cytometry and DNA in the cells was analyzed for DNA adducts using the 32P-postlabeling assay. There was a significant increase (approximately 4-fold) in the level of total adducts in type II cells of rats exposed to DE and CB, compared with sham-exposed rats. While exposure to CB and DE induced the formation of adducts that were not consistently seen in sham-exposed rats, exposure to these materials also appeared to increase the intensity of adducts present in type II cells from sham-exposed rats. These data underscore the importance of investigating molecular dosimetry at the biological level of the cell. We conclude that the type II alveolar cell may be a risk for damage from inhaled DE.

Adenosine Triphosphate↗
PubMed1990

Epithelial progenitor cells in the rat trachea.

Highly pure populations of basal and secretory cells from the rat trachea have been inoculated into denuded tracheal grafts to determine the differentiation pathways of these two cell types. The basal cell inoculum resulted in an epithelium comprised of only basal and ciliated cells, while the secretory cell inoculum gave rise to an epithelium comprised of secretory, basal, and ciliated cells. These results show that, in the rat trachea, the secretory cell is the major progenitorial cell type and the basal cell has only limited progenitorial capacity.

Alcian Blue↗
PubMed1990

On time differences in searching for letters in words and nonwords: do they emerge during the initial encoding or the subsequent scan?

Krueger (1970a, 1970b, 1982) has demonstrated that subjects can search for target letters within words faster than they can complete an equivalent search through nonwords, and he further demonstrated that the effect did not arise during the comparison stage. The present study involved three experiments in which the usual word advantage disappeared either when subjects knew where within a display the target item would appear (i.e., it was always the first letter), or when all the component letters were encoded into memory before the task began (i.e., a memory-search task). These data, in conjunction with Krueger's, where interpreted as localizing at least one (and possibly the only) source of the word-nonword difference in this task to the events that occur during the item-to-item transitions subjects make when scanning the letter arrays. That is, these transitions are faster for words than nonwords, and it was suggested that the time difference may emerge because although all the letters from within a word appear to be available in memory before the scan begins, this seems not to be true for consonant arrays. Given that this is the case, part of the word-nonword difference may be attributable to subsequent encoding events that would be needed for the consonant arrays as the scan moves from letter to letter.

Adult↗
PubMed1989

O6-methylguanine-DNA methyltransferase activity in tissues and cells of the rat respiratory tract.

A product of alkylating agents and DNA, O6-methylguanine (O6-MG), can mispair with thymine, resulting in initiation of a carcinogenic tissue response. O6-alkylguanine-DNA alkyltransferase (AGT) is an acceptor protein responsible for repairing O6-MG. The purpose of our experiments was to characterize in vitro AGT activity in tissues and cells in the respiratory tract, a target tissue for inhaled alkylating agents. Anatomically defined regions throughout the respiratory tract of male F344 rats were obtained. These included two regions of the lateral wall of the left and right nasal airway (maxilloturbinates and ethmoturbinates), trachea, extrapulmonary bronchi and peripheral lung. Alveolar type II cells were also used in these studies. Radioactive 3H-methylated DNA was synthesized for use in all experiments. Removal of [3H]methyl from O6-MG was measured by high-pressure liquid chromatography after incubation for up to 30 min of tissue and cell extracts with the [3H]DNA. With the exception of tracheal and bronchial extracts, all tissues and cells analyzed contained AGT activity, which was found to increase proportionally to the amount of protein added to reaction flasks. AGT activity in tracheal and bronchial extracts was only detected at the highest protein concentration used (1.5 mg protein/ml) and ranged from 10-15 fmol/mg protein. AGT activity was highest in the lung (integral of 75 fmol/mg protein) and a region of the nasal tissue, the ethmoturbinates (integral of 45 fmol/mg protein). AGT activity in the maxilloturbinates was about 50% less than the AGT activity measured in the ethmoturbinates. These data suggest that methylated DNA in specific regions of the rat respiratory tract should be readily repaired, albeit to different extents.

Animals↗
PubMed1989

Inhaled cigarette smoke induces preneoplastic changes in rat tracheal epithelial cells.

Rats were exposed 6 h/day, 5 days/week for 5 weeks to levels of cigarette smoke designed to deposit amounts of particulate per gram of lung similar to those experienced by a heavy smoker. Tracheal epithelial cells were isolated and examined in culture for the presence of preneoplastic variants. Two- to three-fold increases in the frequency of variants were observed in cells isolated from smoke-exposed animals compared to those from air-exposed controls. These results provide an estimate of the frequency of cigarette smoke-induced initiation events in respiratory epithelium that will be useful in further defining the role of cigarette smoke in the development of lung cancer.

Animals↗