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Biomedical subjects

D M Lewis

Publications and source records attributed to D M Lewis.

At least 37 records · Page 2Linked to original sources

Tyrosine kinase activation in response to fungal spores is primarily dependent on endogenous reactive oxygen production in macrophages.

Studies from our laboratory (Shahan, T. A., Sorenson, W. G., and Lewis, D. M. (1994) Environ. Res. 67, 98-104) demonstrated that spores from different fungal species differentially activate rat alveolar macrophages as detected by the measurement of superoxide anion and cytokine production (Shahan, T. A., Siegel, P. D., Sorenson, W. G., Kuschner, W. G., and Lewis, D. M. (1998) Am. J. Respir. Cell Mol. Biol. 18, 435-441). Spores from Aspergillus candidus stimulated production of the highest levels of superoxide anion (5.2 nmol/1.0 x 10(6) alveolar macrophages (AMs)/30 min), followed by those from Aspergillus niger (2.4 nmol/1.0 x 10(6) AMs/30 min) and Eurotium amstelodami (0.4 nmol/1.0 x 10(6) AMs/30 min). The mechanism of this differential activation was studied. Our data demonstrate that the tyrosine kinases p56(Hck), p72(Syk), p77(Btk), p62(Yes), p56(Lck), and p59(Fyn) were specifically activated in response to spores from A. candidus, whereas spores from either A. niger or E. amstelodami activated p56(Hck), p72(Syk), and p77(Btk). Kinetic analysis of specific tyrosine kinases demonstrated that p56(Hck), p72(Syk), and p77(Btk) were activated faster and to a greater extent by spores from A. candidus as compared with spores from E. amstelodami. These data suggest a relationship between reactive oxygen species and tyrosine kinase activation. Treatment of AMs with H(2)O(2) (1 mM) caused the activation of p72(Syk) only, whereas treatment with superoxide dismutase and catalase before treatment with the spores had no effect on tyrosine kinase activation. Incubation with NADPH oxidase inhibitors inhibited both superoxide anion production and the activation of p56(Hck), p72(Syk), and p77(Btk) in response to fungal spores. These data indicate that endogenous reactive oxygen species are necessary for the activation of p56(Hck), p72(Syk), and p77(Btk) by spores; they also indicate that some species of spores are capable of activating tyrosine kinases independent of superoxide anion.

Agammaglobulinaemia Tyrosine Kinase↗

Dynamics of nuclei of muscle fibers and connective tissue cells in normal and denervated rat muscles.

The mitotic activity in muscles of growing rats and the effect of denervation were studied by means of continuous infusion of 5-bromo-2-deoxyuridine (BRDU). Denervated muscles after 10 weeks contained 20 to 60% fewer muscle nuclei than normal; BRDU labeled about 25% of the nuclei of normal soleus and extensor digitorum longus (EDL) and of denervated EDL muscles but only 5% in the denervated soleus muscle. Labeled nuclei persisted in denervated but not in normal muscles. After the main growth period, the turnover of myonuclei was at most 1 to 2% per week. The behavior of connective tissue nuclei was similar to that in muscle fibers. Infusion of BRDU had no effect on contractile properties. It is suggested that the exceptionally rapid atrophy of the denervated rat soleus associated with loss of satellite cells was due to loss of myonuclei and differentiation and fusion of satellite cells. The cause may possibly be that the phase of postdenervation fibrillation is shorter than in other muscles.

Animals↗

Medical hypnosis for temporomandibular disorders: treatment efficacy and medical utilization outcome.

AIM: The aim of this study was to examine the effectiveness of a particular behavioral medicine treatment modality, medical hypnosis, on reducing the pain symptoms of temporomandibular disorders (TMD). METHODS: Twenty-eight patients who were recalcitrant to conservative treatment for TMD participated in a medical hypnosis treatment program and completed measures of their pain symptoms on 4 separate occasions: during wait list, before treatment, after treatment, and at a 6-month follow-up. In addition, pretreatment and posttreatment medical use were examined. RESULTS: Statistical analysis of this open trial suggests that medical hypnosis is a potentially valuable treatment modality for TMD. Patients reported a significant decrease in pain frequency (F [3, 87] = 14.79, P<.001), pain duration (F [3, 87] = 9.56, P<.001), and pain intensity (F [3, 87] = 15.08, P<. 001), and an increase in daily functioning. Analysis suggests that their symptoms did not simply spontaneously improve, and that their treatment gains were maintained for 6 months after hypnosis treatment. Further, after hypnosis treatment, patients exhibited a significant reduction in medical use. CONCLUSION: Medical hypnosis appears to be an effective treatment modality for TMD, in terms of reducing both symptoms and medical use.

Adult↗

Preliminary report on the results of the second phase of a round- robin endotoxin assay study using cotton dust.

In an on-going endotoxin assay study, a two-part interlaboratory endotoxin assay study has been completed. The purpose of the study was to compare the variation in assay results between different laboratories, and, if the variation was high, to see if a common protocol would reduce the variation. In both parts of the study, membrane filters laden with the same approximate amount and type of cotton dust were sent for analysis to laboratories that "routinely" perform endotoxin analyses. First, each of these laboratories performed the analysis using the methodology common to its laboratory. In the second part of the study, membrane filters with cotton dust were again sent to the same laboratories where the analyses were performed as before but with a common extraction protocol. The preliminary results from the first phase of the study have been collected and showed that intra-laboratory variations were small, but large and significant interlaboratory variation was observed. The results were reported elsewhere. The preliminary results from the second part of the study consisting of the data currently collected are presented here. Again, intra-laboratory variations were small, but, also again, large and significant inter-laboratory variation was observed. However, in this part of the study, the range between the highest and lowest average results was narrower than in the first part of the study. Influence of the assay kit type was examined. The variation within assay kit type was small but significant differences in results were observed between assay kit types. The findings suggest that endotoxin concentration in samples can be ranked within laboratories, but not necessarily between laboratories. However, some of the variation between laboratories has been reduced by a common extraction protocol which suggests the possibility of further standardization that may lead to better comparability between laboratories.

Air Pollution, Indoor↗

Natural rubber latex: glove use, sensitization, and airborne and latent dust concentrations at a Denver hospital.

Exposure to natural rubber latex may cause immediate hypersensitivity reactions. Published latex sensitization prevalence rates range from 2.9% to 22% among health care workers, and from 0.12% to about 20% of occupationally unexposed populations. In this study, self-administered questionnaires addressed job and personal characteristics, glove use, and symptoms in two groups of hospital workers: those who regularly used latex gloves and those who did not. Serum was tested for latex-specific immunoglobulin E. Air, surface, and air-filter dust samples for natural rubber latex were collected. The prevalence of latex sensitization was 6.3% in the non-users and 6.1% in the latex glove users (P = 0.9); 81.3% of sensitized workers were atopic compared with 59.5% of non-sensitized workers (P < 0.05). Reporting of work-related hand dermatitis was more common in the latex glove users (23.4%) than in the non-users (4.9%), as were rhino-conjunctivitis (16.3% and 7.9%, respectively, [P < 0.01]), and hand urticaria (9.9% and 2.1%, respectively, [P < 0.01]). There was no significant difference in work-related symptoms between the sensitized and non-sensitized workers. Environmental concentrations of latex were higher in the work areas of the non-sensitized workers, but higher in the clinical than in the non-clinical areas. Occupational latex glove use was not a risk factor for sensitization.

Adult↗

Asthma-like symptoms in wood product plant workers exposed to methylene diphenyl diisocyanate.

BACKGROUND: Diisocyanates, a group of highly reactive chemicals, have frequently been associated with occupational asthma. We evaluated respiratory health in workers at a new wood products manufacturing plant that uses methylene diphenyl diisocyanate (MDI), and was designed and operated with a goal of minimizing worker exposures. METHODS: Health surveys using standardized respiratory questionnaires were done prior to the initial use of diisocyanates in the plant, and semiannually thereafter for a period of 2 years. Other testing included occupational and work practice histories, serial peak flow measurements, spirometry, methacholine challenge, and measurement of specific IgE antibodies to MDI-albumin conjugate. RESULTS: Of 214 plant employees who participated in at least one health survey, a follow-up survey was also available from 178 employees (83%). New-onset asthma-like symptoms (NAS) were reported by 15 of 56 workers (27%) in areas with the highest potential for exposures to liquid MDI monomer and prepolymer, vs 0 of 43 workers in the lowest potential exposure areas (p = 0.001). In the areas with high potential exposure, NAS developed in 47% of workers who had noted MDI skin staining, vs 19% without skin stains (p = 0.07). Working around and cleaning up liquid MDI represented a significant risk for asthma-like symptoms in both current smokers and nonsmokers; work with finished wood products did not. Asthma-like symptoms were associated with variable airflow limitation (odds ratio [OR], 5.0; confidence interval [CI], 1.4 to 18.7) and specific IgE to MDI-albumin (OR, 3.2; CI, 1.1 to 9.0), but not with skin prick tests to common aeroallergens (OR, 1.1; CI, 0.5 to 2.7). CONCLUSIONS: During the first 2 years of operation, in a plant designed and operated to control exposure to diisocyanates, the development of asthma-like symptoms was reported in a relatively high proportion of the employees who worked with liquid MDI. To prevent asthma symptoms among workers, careful control of respiratory tract exposures associated with liquid MDI is important, especially during cleanup activities. Strict limitation of skin contact with diisocyanates may also be necessary.

Adult↗

Factors influencing the documentation of care.

Nursing care plans should provide clear evidence of the quality of patient care provided. A study of a care plan used in a coronary care unit found that nurses were critical of the plan's format. Nurses need adequate education on the use of the chosen care plan and an understanding of the nursing model on which it is based.

Adult↗

Peripheral microvascular parameters in the nephrotic syndrome.

BACKGROUND: Peripheral edema, in combination with severe proteinuria and low serum albumin levels, is pathognomonic of the nephrotic syndrome, yet the exact mechanism of its formation is unknown. Two of the most important of the factors in Starling's forces controlling fluid filtration across the capillary have hitherto not been studied in nephrotic subjects. METHODS: The hydrostatic capillary pressure at the finger nail-fold in actively nephrotic subjects and age and sex matched controls was studied, using direct puncture of the apex of the capillary under video microscopy, and a servonulling apparatus to give a direct measurement of capillary pressure. Capillary filtration capacity (CFC) at the calf was measured noninvasively by a modern derivative of the technique of mercury strain gauge plethysmography. Fifteen nephrotic subjects with a variety of underlying pathological lesions, and age matched controls were studied. RESULTS: Contrary to the assumption of the "overflow" hypothesis of edema formation, there was no evidence of capillary hypertension. The capillary pressure showed no difference between nephrotic subjects and controls: median (range) of 17.6 (12.0 to 24.2) compared with 17.3 (9.0 to 21.6) mm Hg, P = NS. CFC was significantly higher in nephrotic subjects than controls [5.23 (3.28 to 8.52) x 10(-3) versus 3.55 (2.43 to 5.28) x 10(-3) ml/min/100 g/mm Hg, P < 0.01]. CONCLUSIONS: An increase in CFC provides a potentially novel mechanism contributing at least in part to the formation of peripheral edema in the nephrotic syndrome.

Adult↗

Organic dust exposures from work in dairy barns.

Environmental surveys were conducted in 85 barns, predominantly dairy, in central Wisconsin to characterize exposures to organic dusts and dust constituents from routine barn work. Environmental analytes included airborne dusts (total, inhalable inlet, and respirable), particle size distributions, endotoxins, total spore and bacteria counts, viable bacteria and fungi, histamine, cow urine antigen, mite antigen, ammonia, carbon dioxide, and hydrogen sulfide. The geometric mean (GM) concentration of airborne dusts include area total, 0.74 mg/m3; personal inhalable inlet, 1.78 mg/m3, and area respirable, 0.07 mg/m3. Viable bacteria and fungi, spores, endotoxins, histamine, cow urine antigen, and mite antigen were quantifiable constituents of these organic dusts and potential respiratory exposure hazards from routine dairy barn work. Endotoxin concentrations from the inhalable inlet samples ranged from 25.4 endotoxin units per cubic meter of air (EU/m3) to 34,800 EU/m3. The GM endotoxin concentration from these samples, 647 EU/m3, exceeds estimated threshold exposure levels for respiratory health effects. Ammonia was a common irritant quantified in most dairy barns. There were significant correlations between the concentrations of organic dusts and certain dust constituents, although in most instances these correlations were not strong. These sampling results demonstrate the complex nature of organic dusts and provide quantitative description of the exposures to toxic and immunogenic dust constituents during routine barn work.

Air Microbiology↗

Limb capillary filtration coefficient in human subjects: the importance of the site of measurement.

Capillary filtration coefficient is a critical determinant of fluid flux across the microvascular wall. Changes in capillary filtration coefficient have been described in a number of disease processes. Measurement is typically made by venous occlusion plethysmography using either the upper or lower limb, but a variety of measurement protocols have been used and the importance of the site of measurement remains unclear. In this study, forearm and calf capillary filtration coefficient were measured in healthy volunteers, either simultaneously (group A; n = 11) or sequentially in random order (group B; n = 11) using venous occlusion plethysmography, with the subject supine and the limb at heart level. In both studies capillary filtration coefficient was significantly higher when measured at the forearm than at the calf (group A: 6.1 +/- 1.0 versus 3.7 +/- 1.1 x 10(-3) ml min(-1) mmHg(-1) 100 ml(-1) (mean +/- SD), p < 0.01; group B: 5.1 +/- 1.2 versus 3.2 +/- 1.1 x 10(-3) ml min(-1) mmHg(-1) 100 ml(-1), p < 0.01). Isovolumetric venous pressure (the maximum pressure at which there is neither net filtration nor absorption at the microvascular wall) was similar in upper and lower limbs in both groups of subjects. We conclude that limb capillary filtration coefficient is dependent on the site of measurement. Caution is required when comparing data recorded at different sites even if corrected for the volume of soft tissue under study.

Adult↗

Molecular markers of acute upper airway inflammation in workers exposed to fuel-oil ash.

Biomarkers in nasal lavage (NL) fluid may be useful in determining the presence and severity of upper airway inflammation. We studied 18 boilermakers overhauling a large, oil-fired boiler and 11 utility workers who served as controls for 6 wk. NL was performed before (NL1), during (NL2), and after (NL3) the overhaul. We measured nasal fluid levels of interleukins 6 (IL-6) and 8 (IL-8), eosinophilic cationic protein (ECP), and myeloperoxidase (MPO) as markers of response to fuel-oil ash exposure. In boilermakers, MPO was elevated during boiler work versus preboiler work (mean = 33.8 versus 22.7 ng/ml, p < 0.05), and at the 2-wk postexposure lavage (NL3) it had declined to 24.2 ng/ml (p = 0.08). Mean IL-8 levels increased in boilermakers between NL1 and NL2 (mean = 83.8 versus 134.8 pg/ml, p < 0.05), then decreased at NL3 (mean = 134.8 versus 89.0 pg/ml, p < 0.05). Nasal fluid vanadium increased in boilermakers between NL1 and NL2 (median < 1.0 versus 4.7 ppb, respectively, p < 0.05), then decreased at NL3 (median, 4.7 versus < 1.0 ppb, respectively, p < 0. 05). Levels of IL-6 and ECP did not change significantly during the study. Utility workers showed no significant change in any marker during the study period. Particulate matter < 10 micro(m) (PM10) levels were higher for boilermakers than for utility workers before boiler work (geometric mean (GM) = 0.40 versus 0.10 mg/m3, p < 0.05). This difference was more significant during boiler work (GM = 0.47 versus 0.13 mg/m3, p < 0.001). Ozone levels were low during the study. These data suggest that exposure to fuel-oil ash results in acute upper airway inflammation, potentially mediated by increased IL-8 levels and the recruitment and activation of polymorphonuclear leukocytes. These changes were associated with significantly increased PM10 levels and concentrations of upper airway vanadium.

Adult↗

Concentration- and time-dependent upregulation and release of the cytokines MIP-2, KC, TNF, and MIP-1alpha in rat alveolar macrophages by fungal spores implicated in airway inflammation.

Inhalation of fungal spores has been shown to cause primary or secondary infection and respiratory inflammation and diseases such as allergic alveolitis, atopic asthma, and organic dust toxic syndrome, which are rarely reported in the absence of predisposing factors. Biochemical and molecular markers of inflammation were measured in rat bronchial alveolar lavage cells (> 95% macrophages) following stimulation with fungal spores isolated from pathogenic and nonpathogenic fungi that have been implicated in airway inflammation. The results of this study demonstrate that mRNA transcripts for the C-X-C branch of the PF4 superfamily are differentially upregulated over those of the C-C mediators in a time- and concentration-dependent manner. Macrophage inflammatory protein (MIP)-2 and KC were differentially upregulated over the acute phase inflammatory cytokines MIP-1alpha and tumor necrosis factor-alpha (TNF-alpha) in rat alveolar macrophages stimulated with fungal spores from Aspergillus candidus, Aspergillus niger, Eurotium amstelodami, and Cladosporium cladosporioides. Spores from Aspergillus terreus and Penicillium spinulosum failed to stimulate an increase of any cytokine mRNA, whereas those from Aspergillus fumigatus stimulated the upregulation of MIP-2, KC, TNF-alpha, and MIP-1alpha mRNAs. Over time, A. fumigatus stimulated increasing KC production until 24 h, when production levels increased slightly, then leveled off when measurements ceased at 36 h. Latex spheres stimulated modest amounts of MIP-2 and transforming growth factor-beta only. These observations suggest that the inflammatory cytokines MIP-2 and KC may be involved in the inflammation arising from the inhalation of fungal spores in a time- and concentration-dependent manner.

Animals↗

Adjuvant effect of respiratory irritation on pulmonary allergic sensitization: time and site dependency.

It has been suggested that airway irritation, by acting as an adjuvant, as well as producing damage, may be an important factor related to asthma. The present study examined the window of time following acute upper and lower airway irritant exposure to determine the period of increased risk of immunological sensitization. Brown Norway rats were exposed to 87 ppm NO2 or 1000 ppm NH3 for 1 hr. A 30-min ovalbumin (OVA) exposure of 18.14 microg/liter air was given at various times based upon the time course of irritant associated inflammatory response (either immediately prior to or 1 or 7 days after the irritant exposure). OVA-only, NO2-only or NH3-only controls, and saline controls were also studied. Weekly booster exposures of OVA (or saline) were given. Circulating OVA-specific IgE, IgA, and IgG levels were quantified periodically during the 6 weeks of the study. Bronchoalveolar lavage (BAL) was also performed to examine the inflammatory response to allergic and irritant challenge. Significant increases in OVA-specific IgE, IgG, and IgA antibody titers were seen in rats given the sensitizing OVA exposure within 1 day of the NO2, but not NH3 exposures. Enhancement of cellular infiltrate in BAL was noted in groups given the sensitizing OVA exposure within 1 day of the NO2 or NH3. It is concluded that the inflammatory and immunological response to antigen exposure can be modified by the site of respiratory tract irritation and the relative times of irritant and antigen exposure.

Adjuvants, Immunologic↗

Effects of long-term phasic electrical stimulation on denervated soleus muscle: guinea-pig contrasted with rat.

Guinea-pig soleus muscles were denervated and electrically stimulated for periods of 43 to 66 days. Stimuli were in 1 s bursts of 40 Hz pulses, repeated every 5 min. Other guinea-pigs were denervated for 82 days without stimulation and, in a third group, the soleus muscle was necrotized and allowed to regenerate without reinnervation for 13-15 days. Isometric and isotonic recordings were made in vivo. Denervated guinea-pig muscles were embedded in epoxy resin for light and electron microscopy. Chronic stimulation of denervated guinea-pig soleus had no effects on the prolonged twitch or on reduced maximal shortening velocity, maximal rate of rise of tension and tetanic force. This contrasts with the slow-to-fast conversion produced by denervation and denervation-stimulation of rat soleus. Loss of force was much greater in rat than guinea-pig after denervation, and chronic stimulation increased force in rat to the same level as in guinea-pig after denervation (with or without stimulation). Eighty-day denervated guinea-pig soleus did not reveal those morphological signs of fibre breakdown and regeneration which are prominent in denervated rat soleus muscles. Those changes in rat resembled aneurally regenerated muscles in several aspects, especially the increased incidence of fibres with internal myo-nuclei which did not appear in guinea-pig soleus after denervation. Aneurally regenerated guinea-pig soleus became fast like aneurally regenerated rat muscle. Our data are compatible with the hypothesis that slow-to-fast transformation of denervated rat soleus is not directly brought about by chronic stimulation but by de-novo formation of fast-contracting regenerated fibres. The persistence of fibrillation in guinea-pig but not rat after denervation may account for the species difference.

Animals↗