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T Gordon

Publications and source records attributed to T Gordon.

At least 55 records · Page 3Linked to original sources
PubMed1999

A critical evaluation of enzyme immunoassays for detection of antinuclear autoantibodies of defined specificities. I. Precision, sensitivity, and specificity.

OBJECTIVE: To determine the performance characteristics of enzyme-based immunoassay (EIA) kits for the detection of antinuclear and other autoantibodies of defined specificities. METHODS: Nine manufacturers of EIA kits to detect antibodies of defined specificities participated in a study in which they received coded sera from the Centers for Disease Control and Prevention. These coded sera contained different dilutions of antibody of one specificity mixed with sera containing antibodies of other specificities. The manufacturers were asked to use their standard technology to determine antibody content and send the data to a committee of the International Union of Immunological Societies for analysis. The data were analyzed for sensitivity and specificity in the detection of anti-double-stranded DNA (anti-dsDNA), anti-single-stranded DNA, antihistone, anti-Sm, anti-U1 RNP, anti-SSA/Ro, anti-SSB/La, anti-Scl-70 (DNA topoisomerase I), anticentromere, and anti-Jo-1 antibodies. In addition, replicate samples were included in the coded sera to evaluate the precision of each EIA method. RESULTS: Lack of sensitivity and specificity was most evident in the anti-dsDNA and anti-Sm kits, although 2 kits for anti-dsDNA achieved acceptable sensitivity and specificity. Generally, anti-SSA/Ro, anti-SSB/La, anti-Scl-70, anticentromere, and anti-Jo-1 kits performed well. Many false-positive results were obtained with a multiple myeloma serum containing cryoprecipitates, but multiple myeloma sera without cryoprecipitates presented no problem in the EIA system. Precision, based on evaluation of replicate samples, varied from very good to poor. CONCLUSION: No single manufacturer was clearly superior to others in terms of their products' overall sensitivity, specificity, and precision. Areas that needed improvement were in kits for the detection of antibodies to dsDNA and to Sm antigen. Some EIA kits achieved good sensitivity and specificity. Individual manufacturers were informed of the performance of their respective kits so they could take measures to correct perceived deficiencies and thus improve the reliability of a group of important diagnostic assays used in the evaluation of systemic rheumatic diseases.

Antibodies, Antinuclear↗
PubMed1999

Innervation and properties of the rat FDSBQ muscle: an animal model to evaluate voluntary muscle strength after incomplete spinal cord injury.

Muscles innervated from spinal segments close to the site of a human spinal cord injury are often under voluntary control but are weak because they are partially paralyzed and partially denervated. Our objective was to develop an animal model of this clinical condition to evaluate strategies to improve voluntary muscle strength. To do so, we examined the spinal and peripheral innervation of the flexor digitorum superficialis brevis quinti (FDSBQ) muscle of the rat foot, characterized the muscle and motor unit properties, and located the FDSBQ motoneurons. Retrograde labeled motoneurons were in L4 to L6 spinal cord. Unilateral stimulation of L4 to S1 ventral roots and recording of evoked force showed that FDSBQ motor axons exited via two ventral roots (L5 and L6 or L6 and S1) in 38% of rats and via one ventral root in 62% of rats. FDSBQ motor axons traveled via two peripheral nerves, the lateral plantar (76% of axons) and sural nerves (24%). Each ventral root contributed motor axons to each nerve branch. Thus, by combining conduction block of one peripheral nerve to induce partial muscle paralysis and ventral root section to induce partial denervation, it is possible to produce in one rat muscle the consequences of many human cervical spinal cord injuries. FDSBQ muscles and motor units were mainly fast-twitch, fatigable, and composed of fast-type muscle fibers. The narrow range of motor unit forces (1-13 mN), the low mean twitch force (5.1 +/- 0.3 mN), and the large number of motoneurons (31 +/- 4) suggest that rat FDSBQ muscle is a good model of distal human musculature which is frequently influenced by spinal cord injury. We conclude that the FDSBQ muscle and its innervation provide a useful animal model in which to study the consequences of many spinal cord injuries which spare some descending inputs but also induce substantial motoneuron death near the lesion.

Animals↗
PubMed1999

A centrifugal particle concentrator for use in inhalation toxicology.

Epidemiologic studies have provided strong evidence that episodic exposure to ambient particulate matter is associated with increases in morbidity and mortality. These adverse effects have been demonstrated at concentrations far below the National Ambient Air Quality Standard (NAAQS), and thus, the biological plausibility of these effects has been questioned. For the purpose of exposing test animals to relevant and reproducible exposure concentrations of ambient particulate matter (PM), we have developed a simple and inexpensive concentrator system that can concentrate ambient particles 10-fold. A high-volume blower is used to deliver ambient air to the inlet manifold of a centrifugal concentrator and the entrained particles travel along a concentric annulus formed by a stationary solid outer cylinder and a porous inner cylinder rotating at high speed (up to 12,500 rpm). Suction applied at one end of the porous shaft causes the dispersion medium (air) to pass through the porous cylinder and into the shaft. Since the rotational velocity of airborne particles is comparable to that of the rotating cylinder near its surface, the particles move radially outward due to the centrifugal force, in addition to their motion laterally along the cylinder and inward due to the suction of air into the rotating porous cylinder. The particles reach their highest concentration near the outlet manifold, where they enter the exposure chamber under positive pressure ( approximately 0.4 cm H2O). Except for coarse particle loss due to impaction and diffusional loss of ultrafine particles in the concentrator, the increase in particle concentration is the ratio of the flow rates for the inlet air and the air delivered to the exposure chamber. We have used the centrifugal concentrator to deliver concentrated ambient urban PM to a nose-only exposure chamber and examined the concentrating effect across ambient particle sizes.

Air↗
PubMed1999

Factors contributing to the acute and subchronic adverse respiratory effects of machining fluid aerosols in guinea pigs.

Several physical, chemical, and microbial factors are potential contributors to the adverse pulmonary effects associated with occupational exposure to machining fluid aerosols. The present study examined the relative toxicity of 3 major classes of machining fluids (soluble, semi-synthetic, and synthetic) as well as that of unused (fresh) versus used (grab samples taken from manufacturing sites) machining fluids. Pulmonary function and changes in cellular and biochemical indices in bronchoalveolar lavage fluid were examined during and 24 h after exposure, respectively. Statistically significant differences in toxicity were observed in guinea pigs exposed for 3 h to respirable aerosols of unused machining fluids (semi-synthetic > soluble >> synthetic). In addition, greater toxicity was observed in animals exposed to used, machining fluid aerosols compared to unused fluids. Moreover, within the used machining fluid types, significantly greater adverse effects were observed in animals exposed to poorly maintained fluids (i.e., heavy microbial contamination) versus well-maintained fluids. Changes in biochemical and cellular parameters in bronchoalveolar lavage fluid occurred after a single exposure to 5 mg/m3 of the poorly maintained used machining fluid aerosols. Changes in inflammation but not LDH and protein were observed in animals repeatedly exposed to semi-synthetic machining fluid aerosols. A statistically significant increase in lavage fluid neutrophils was observed in guinea pigs exposed to 5 mg/m3 used, semi-synthetic machining fluid aerosols for 4 weeks. In separate experiments, physicochemical properties of unused machining fluids were found to contribute to the production of adverse effects. Adjustment of the alkaline and hypotonic nature of the unused semi-synthetic machining fluid to isotonicity and pH 7 significantly reduced adverse effects. Together, these findings strongly suggest that multiple factors contribute to the adverse respiratory effects associated with occupational exposure to machining fluid aerosols.

Administration, Inhalation↗
PubMed1998

Ambient particulate matter causes activation of the c-jun kinase/stress-activated protein kinase cascade and DNA synthesis in lung epithelial cells.

Numerous epidemiological studies have demonstrated a positive association between ambient air pollution and adverse health effects including respiratory morbidity, asthma, and lung cancer. It has been suggested in some experimental studies that airborne particulate matter (PM) can produce inflammatory effects, but nothing is known about the possible proliferative and carcinogenic effects of these particles on cells of the lung. We show here that exposure of pulmonary epithelial cells, a cell type affected in acute lung injury, asthma, and lung carcinomas, to nontoxic concentrations of PM in vitro results in increases in c-jun kinase activity, levels of phosphorylated cJun immunoreactive protein, and transcriptional activation of activator protein-1-dependent gene expression. These changes are accompanied by elevations in numbers of cells incorporating 5'-bromodeoxyuridine, a marker of unscheduled DNA synthesis and/or cell proliferation. Data here are the first to demonstrate that interaction of ambient PM with target cells of the lung initiates a cell signaling cascade related causally to aberrant cell proliferation and carcinogenesis.

Air Pollution↗
PubMed1998

Incomplete rematching of nerve and muscle properties in motor units after extensive nerve injuries in cat hindlimb muscle.

1. Motor units were characterized in partially denervated or completely denervated and reinnervated cat medial gastrocnemius (MG) muscles where the number of innervating motor axons was severely reduced to determine (1) to what extent the nerve and muscle properties are rematched in enlarged motor units, (2) whether the normal size relationships between axon size, unit tetanic force and contractile speed are re-established, and (3) whether the type of nerve injury and/or repair affects the re-establishment of nerve and muscle properties. 2. Single MG units were sampled in (1) partially denervated muscles and in reinnervated muscles after either (2) crushing or (3) transecting the nerve and suturing its proximal end to either the distal nerve stump (N-N), or (4) directly to the muscle fascia (N-M). 3. The majority (75-88 %) of motor units in all muscles were classified as S (slow), FR (fast fatigue resistant), FI (fast fatigue intermediate) and FF (fast fatigable). However, there was an increased number of FI and unclassifiable motor units compared to normal. These results suggest that motor unit properties are not entirely regulated by the reinnervating motoneurone. 4. Despite more overlap in the range of unit force between different motor unit types the tetanic force of each type increased in all muscles when reinnervated by few (< 50 %) motor axons. This increase in unit force was due to an expansion in motor unit innervation ratio. 5. The normal relationships between axon size, unit tetanic force, and contractile speed were re-established in all muscles except when reinnervated by < 50 % of their normal complement of motor units after N-M suture. This lack of correlation was due to the reduced fast glycolytic (FG) fibre size and the proportionately greater increase in force of the S units. 6. After reinnervation the ranges in fibre cross-sectional area within single FF units were very similar to those found within the entire FG fibre population. 7. These results show that when few axons make functional connections in partially denervated or reinnervated muscles the normal relationships between axon size and motor unit contractile properties are re-established provided the nerves regenerate within the distal nerve sheath. This rematching of motoneurone size and motor unit contractile properties occurs primarily because the size of the motor axon governs the number of muscle fibres it supplies.

Animals↗
PubMed1998

Force and stiffness of old dystrophic (mdx) mouse skeletal muscles.

It has recently been suggested, based on studies of tissue pathology, that the limb muscles of old mdx mice may be a good model for the muscular changes seen in human Duchenne muscular dystrophy. To test this hypothesis, we measured force and stiffness of soleus and extensor digitorum longus (EDL) muscles of old (20-21 months) mdx mice and age-matched controls. The mdx and control muscles generated similar twitch, tetanic, and eccentric forces. They were also equally stiff. The results show that the mechanics of aged mdx limb muscles differ greatly from Duchenne muscular dystrophy in humans, and disagree with the hypothesis.

Aging↗
PubMed1998

Expression of metallothionein protein in the lungs of Wistar rats and C57 and DBA mice exposed to cadmium oxide fumes.

Chronic exposure to inhaled cadmium (Cd) has been shown to induce lung tumors in rats (Wistar strain) but not in mice (NMRI strain). The protein metallothionein (MT) plays an important role in Cd detoxification, and it has been suggested that differential inducibility of pulmonary MT may lead to interspecies susceptibility differences to inhaled Cd. Interstrain differences in the pulmonary response of the MT gene to Cd stimuli have not been examined in rats or mice. We compared pulmonary MT expression in Wistar Furth (WF) rats with that in DBA and C57 mice, following a single 3-h exposure to CdO fumes containing 1 mg Cd/m3. Induction of the MT gene was assessed by the levels of MT-I and MT-II transcripts, MT-protein content, and number of MT-labeled alveolar and bronchiolar epithelial cells immediately after Cd exposure and 1, 3, and 5 days later. Control animals were exposed to air/argon furnace gases. We observed differential intra- and interspecies inducibility of the MT gene in the lung following Cd inhalation. DBA mice exhibited greater levels of MT-mRNA, mainly for the MT-I isoform, MT-protein content, and number of MT positive cells relative to C57 mice. WF rats showed lower transcription and translation responses of the MT gene upon Cd stimuli than C57 mice. The present results, in concert with our previous findings of higher lung cell proliferation in Cd-exposed C57 relative to DBA mice, predict greater susceptibility of C57 to the carcinogenic effects of inhaled Cd. Furthermore, the low transcriptional and translation responses of the MT gene to Cd stimuli in WF rats might explain the higher susceptibility of this rat strain to develop malignant lung tumors after chronic exposure to Cd via inhalation. Parallel to our findings in mice, differences in the responsiveness of lung MT gene may exist across rat strains. Thus intraspecies genetic variability in pulmonary MT may influence the susceptibility of rats or mice to lung carcinogenesis induced by inhalation of Cd compounds.

Administration, Inhalation↗
PubMed1998

Pulmonary and cardiovascular effects of acute exposure to concentrated ambient particulate matter in rats.

To examine the biological plausibility of the adverse health effects of ambient particulate matter (PM), we have studied the cardio-pulmonary effects of PM in an animal model of pulmonary hypertension. Normal and monocrotaline-treated rats were exposed, nose-only, for 3 h to filtered air or concentrated ambient PM. At 3 h--but not 24 h--post-exposure, the percentage of neutrophils in peripheral blood was significantly elevated in PM-exposed animals while the percentage of lymphocytes was decreased with no change in white blood cell counts. These changes in white blood cell differential occurred in both normal and monocrotaline-treated animals. Small, but consistent changes in heart rate, but not core temperature, were observed after exposure to concentrated ambient PM. Pulmonary injury, as evidenced by increased protein levels in lavage fluid, occurred only in monocrotaline-treated animals exposed to > 360 microg/m3 PM. The observed pattern of hematological and cardiac changes suggests an activation of the sympathetic stress response.

Air Pollutants↗
PubMed1998

HLA class II phenotype controls diversification of the autoantibody response in primary Sjögren's syndrome (pSS).

The coexistence of anti-La (SS-B) and anti-Ro (SS-A) autoantibodies in pSS is probably explained by intermolecular spreading of autoimmunity toward different components of the La/Ro ribonucleoprotein (RNP). In order to evaluate the role of the HLA class II phenotype in controlling diversification of this autoantibody response, 80 patients with pSS were typed by polymerase chain reaction sequence-specific oligonucleotide (PCR-SSO) at the HLA class II loci DRB1, DQA1 and DQB1. Serum samples were examined for anti-La and anti-Ro by counterimmunoelectrophoresis and by ELISA using purified recombinant La and 60-kD Ro proteins. Patient sera were classified according to the extent of diversification of the anti-La, anti-Ro response including the presence or absence of precipitating anti-La antibodies. Immunogenic characteristics of these stratified groups were then studied. All patients with pSS, with or without autoantibodies to Ro and La, were found to have at least one of the HLA-DRB1 types DR2, DR3 or DR5. The HLA DR3-DQA1*0501-DQB1*02 (DR3-DQ2) haplotype was primarily associated with a diversified La/Ro RNP response containing precipitating autoantibodies to La (P<0.001); whereas the haplotype HLA DR2-DQA1*0102-DQB1*0602 (DR2-DQ1) was associated with a less diversified La/Ro RNP response containing non-precipitating (restricted epitope) anti-La autoantibodies (P<0.001). Anti-La-positive patients lacking both HLA-DR2 and HLA-DR3 all expressed the HLA-DQA1*0501 allele, which was present at increasing frequency with greater diversification of the anti-La/Ro autoantibody response. The association of distinct HLA haplotypes with different degrees of autoantibody diversification in patients with pSS suggests a model of HLA-restricted presentation of La/Ro peptide determinants to autoreactive helper T cells. We propose that non-precipitating anti-La responses are driven by limited intermolecular help from DR2-DQ1-restricted T helper cells recognizing Ro determinants. On the other hand, we speculate that the more diversified, precipitating anti-La responses obtain more efficient cognate T help from DR3-DQ2-restricted T helper cells recognizing La determinants, where HLA-DQA1*0501 may be a critical determinant for antigen presentation.

Alleles↗
PubMed1998

Lytic skull metastasis from a follicular thyroid carcinoma in a child.

We present a case of solitary lytic skull metastasis from a follicular thyroid carcinoma in a child. Salient clinical features, radiological findings, and histological distinctions of the metastatic skull tumor are described. Excision of the skull tumor followed by total thyroidectomy and (131)I-radioablation therapy has resulted in good short-term outcome. This is the first published report of a metastatic skull lesion from a follicular thyroid carcinoma in a child. Such a malignant lesion can radiologically mimic a benign skull tumor and should be considered in the differential diagnosis of a solitary lytic skull lesion with a sclerotic margin.

Adenocarcinoma, Follicular↗
PubMed1997

Innervation ratio and motor unit force in large muscles: a study of chronically stimulated cat medial gastrocnemius.

1. The present study uses chronic low frequency stimulation of cat medial gastrocnemius (MG) muscle to investigate the relative contribution of innervation ratio to the wide range of motor unit force in large mammalian muscles by reducing the normal variation in muscle fibre cross-sectional area and specific force. 2. Isometric force recordings from isolated and physiologically characterized motor units were made 42-240 days after stimulation. Innervation ratio, fibre area and fibre type (I, II A, II B) were determined in one glycogen-depleted motor unit per muscle. 3. After 42 days of stimulation, all motor units were non-fatigable and were classified as either slow (S) or fast-fatigue resistant (FR). Despite the absence of fast-fatigable (FF) motor units, all three muscle fibre types were present, as identified according to their myofibrillar ATPase reactivity. After 143 days, all motor units and muscle fibres were classified as type S and type I, respectively. 4. A rapid decline in muscle and motor unit force to 30% of normal values after 42 days of chronic stimulation was accounted for by a reduction in muscle fibre area. Fibre areas did not change further with longer periods of stimulation but type II fibres were converted to type I. All stimulated muscle fibres were the size of normal type I fibres; the size of the fibres within single motor units covered the full range of the muscle fibre population. 5. In long-term stimulated muscles (> 100 days) when all muscle fibres were type I and all motor units type S, only differences in innervation ratio could account for the remaining range in motor unit force. Estimates of this range from the minimum and maximum values recorded and from values of tetanic force between the 5th and 95th percentiles indicate that the range in innervation ratio in the MG muscles is at least 15-fold and may be as large as 38-fold. Enumerations of glycogen-depleted muscle fibres from single motor units were consistent with this explanation. 6. The findings provide evidence that there is a wide range of innervation ratios in large muscles, which can account for the large range in motor unit forces in the muscles. Since motor unit force and innervation ratio vary with motoneurone size, these studies provide further support that the size of the peripheral field of innervation of motoneurones is related to their size.

Animals↗
PubMed1997

The expression of the low affinity nerve growth factor receptor in long-term denervated Schwann cells.

Schwann cells in the distal stump of injured peripheral nerves synthesize the low affinity nerve growth factor receptor (p75). In this study we used short-term (1 week) and long-term (1-12 months) transected distal sciatic nerves of rats to determine the variations of p75 expression by using immunocytochemistry and in situ hybridization. Semi-quantitative analysis revealed that the synthesis of the protein product of the p75 gene is rapidly enhanced to reach a peak within the 1 month after denervation. After that it gradually decreased and was barely detectable 6 months following denervation. Double immunocytochemistry for p75 and the S100 protein revealed that p75 immunoreactivity is confined to the Schwann cells. Quantitative analysis of our in situ hybridization experiments revealed that the upregulation of the p75 mRNA parallels the enhanced synthesis of the corresponding protein and reaches a peak within 1 month, which is maintained until the second month after the transection and declines thereafter to reach background levels at 4 months. The electron microscopic observations reveal that the increase in the number of nuclei in the distal stump belong to severely atrophied Schwann cells and fibroblasts. Since the presence of p75 in the Schwann cells is necessary for reinnervation, our results indicate that, based on the expression of p75, the Schwann cells will provide a most suitable environment for the regenerating axons up to the first month. At later stages the ability of the Schwann cells to synthesize p75 and cell adhesion proteins such as N-CAM and GAP 43 decreases which may be one of the factors that contribute to poor functional recovery if the regenerating axons reach the distal stump after long periods of time.

Animals↗
PubMed1997

Reference sera for antinuclear antibodies. II. Further definition of antibody specificities in international antinuclear antibody reference sera by immunofluorescence and western blotting.

OBJECTIVE: To define the fine specificity of the 10 reference sera used for determination of antinuclear antibodies (ANA) and ANA subsets which are available from the Arthritis Foundation (AF) and from the Centers for Disease Control and Prevention (CDC). METHODS: AF/CDC sera were assessed by experienced laboratory staff, using indirect immunofluorescence and Western blotting. RESULTS: The original assignment of fluorescence patterns to 4 reference sera was confirmed, and the fluorescence intensities were determined using reference fluorescent beads. On Western blots, sera AF/CDC2 (anti-SS-B/La) and AF/CDC7 (anti-SS-A/Ro) did not detect Ro antigens, sera AF/CDC9 and AF/CDC10 appeared to be monospecific anti-Scl-70 and anti-Jo-1 sera, respectively, serum AF/CDC4 (anti-U1 small nuclear RNP) recognized the 70-kd band, and serum AF/CDC5 recognized the Sm antigen with its multiple bands. Semiquantitative analyses revealed that AF/CDC5, AF/CDC2, and AF/CDC10 were strongly reactive sera, whereas AF/CDC4 and AF/CDC9 were much weaker and should be used at lower dilutions on Western blots. CONCLUSION: The AF/CDC ANA reference sera, originally described as reference reagents for indirect immunofluorescence and double immunodiffusion techniques, are also useful for Western blotting. The data presented herein further support the use of these sera for reference purposes.

Antibodies, Antinuclear↗
PubMed1997

Range of antinuclear antibodies in "healthy" individuals.

OBJECTIVE: To determine the range of antinuclear antibodies (ANA) in "healthy" individuals compared with that in patients with systemic lupus erythematosus (SLE), systemic sclerosis (SSc; scleroderma), Sjögren's syndrome (SS), rheumatoid arthritis (RA), or soft tissue rheumatism (STR). METHODS: Fifteen international laboratories experienced in performing tests for ANA by indirect immunofluorescence participated in analyzing coded sera from healthy individuals and from patients in the 5 different disease groups described above. Except for the stipulation that HEp-2 cells should be used as substrate, each laboratory used its own in-house methodology so that the data might be expected to reflect the output of a cross-section of worldwide ANA reference laboratories. The sera were analyzed at 4 dilutions: 1:40, 1:80, 1:160, and 1:320. RESULTS: In healthy individuals, the frequency of ANA did not differ significantly across the 4 age subgroups spanning 20-60 years of age. This putatively normal population was ANA positive in 31.7% of individuals at 1:40 serum dilution, 13.3% at 1:80, 5.0% at 1:160, and 3.3% at 1:320. In comparison with the findings among the disease groups, a low cutoff point at 1:40 serum dilution (high sensitivity, low specificity) could have diagnostic value, since it would classify virtually all patients with SLE, SSc, or SS as ANA positive. Conversely, a high positive cutoff at 1:160 serum dilution (high specificity, low sensitivity) would be useful to confirm the presence of disease in only a portion of cases, but would be likely to exclude 95% of normal individuals. CONCLUSION: It is recommended that laboratories performing immunofluorescent ANA tests should report results at both the 1:40 and 1:160 dilutions, and should supply information on the percentage of normal individuals who are positive at these dilutions. A low-titer ANA is not necessarily insignificant and might depend on at least 4 specific factors. ANA assays can be a useful discriminant in recognizing certain disease conditions, but can create misunderstanding when the limitations are not fully appreciated.

Adult↗
PubMed1997

Comparison of inflammatory lung responses in Wistar rats and C57 and DBA mice following acute exposure to cadmium oxide fumes.

Inhalation of cadmium oxide (CdO) is a significant form of human exposure to cadmium (Cd). Furthermore, there is epidemiological and experimental data relating Cd inhalation with lung cancer. Animal studies indicate that rats are more susceptible to Cd-induced lung cancer than mice, but interstrain sensitivity differences to Cd-induced pulmonary inflammation or carcinogenesis have not been addressed in either species. We compared pulmonary inflammatory processes in Wistar Furth (WF) rats with those in C57 and DBA mice exposed to freshly generated CdO fumes in nose-only inhalation chambers. Animals were exposed to 1 mg Cd/m3 for 3 hr and terminated immediately or 1, 3, and 5 days after exposure. Control animals were exposed to air/argon furnace gases. Cd-induced lung injury was assessed by bronchoalveolar lavage fluid (BALF) analyses, histopathology, and immunohistochemical detection of cell proliferation. Inhalation of CdO resulted in pulmonary inflammatory processes that varied widely across species and strains. C57 mice responded with faster and greater influx of neutrophils and proliferation of alveolar macrophages, type II epithelial cells, and bronchiolar epithelial cells compared to DBA mice or WF rats. DBA mice retained a greater percentage of inhaled Cd in the lungs and presented higher levels of BALF protein than C57 mice or rats. In comparison to mice, WF rats responded with a more transient inflammatory response in BALF parameters and higher degree of acute inflammation in lung tissue. The more pronounced proliferation of alveolar and bronchiolar epithelial cells observed in C57 mice might indicate higher susceptibility of this mice strain to Cd-induced lung carcinogenesis compared to DBA mice or WF rats. Furthermore, the present results of fewer inflammatory cells and lower proliferation of epithelial cells in DBA mice in association with our previous observation of higher Cd-induced metallothionein protein in this strain suggest that DBA might be less susceptible to the pulmonary carcinogenic effects of inhaled Cd than C57 mice or WF rats. We conclude that mice might not necessarily be more resistant than rats to the carcinogenic effects of inhaled Cd, since intraspecies susceptibility differences are strongly suggested by the present data. An extrapolation of this conclusion is that genetic variations in the human population may determine individual sensitivity differences to inhaled Cd.

Administration, Inhalation↗
PubMed1997

Metal fume fever: characterization of clinical and plasma IL-6 responses in controlled human exposures to zinc oxide fume at and below the threshold limit value.

Results from animal and preliminary human exposure studies have called into question whether the 5 mg/m3 8-hour time-weighted average threshold limit value (TLV) for zinc oxide fume is sufficient to protect workers against metal fume fever. The objectives of this study were to determine the clinical effects of exposures to low concentrations of zinc oxide and to ascertain whether these exposures elevated circulating levels of specific cytokines, which could account for the symptoms of the metal fume fever syndrome. Thirteen resting naive subjects inhaled, on separate days, air and 2.5 and 5 mg/m3 of furnace-generated zinc oxide fume for 2 hours. Subjects recorded symptoms and temperature and had blood drawn before and after each exposure. The mean (+/- SE) maximum rise in oral temperature at 6 to 12 hours after exposure was 1.4 +/- 0.3 degrees F after 5 mg/m3, compared with 0.6 +/- 0.5 degrees F after air exposure (P < 0.05). Mean temperature was also elevated after exposure to 2.5 mg/m3 zinc oxide (1.2 +/- 0.3 degrees F). In a parallel fashion, plasma levels of interleukin 6 (IL-6), a pyrogen, were significantly elevated after exposure to 5 mg/m3 zinc oxide. Mean IL-6 values (pg/mL) at pre-exposure and at 3 and 6 hours post-exposure were 1.9 (+/- 0.6), 2.8 (+/- 0.7), and 2.9 (+/- 0.6), respectively, on the air day and 1.6 (+/- 0.6), 4.4 (+/- 1.2), and 6.4 (+/- 1.1) on the 5 mg/m3 zinc oxide day. Zinc oxide exposure did not significantly affect plasma levels of tumor necrosis factor. Total symptom scores peaked 9 hours after the 5 mg/m3 zinc oxide exposure. Myalgias, cough, and fatigue were the predominant symptoms reported. Inhalation of zinc oxide for 2 hours at the current TLV of 5 mg/m3 produces fever and symptoms along with elevation in plasma IL-6 levels.

Adult↗