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Biomedical subjects

D E Banks

Publications and source records attributed to D E Banks.

At least 37 records · Page 2Linked to original sources
PubMed1993

Altered calcium homeostasis and cell injury in silica-exposed alveolar macrophages.

There is evidence to suggest that cell injury induced in alveolar macrophages (AM) following phagocytic activation by silica particles may be mediated through changes in intracellular free calcium [Ca2+]i. However, the mechanism of silica-induced cytotoxicity relative to [Ca2+]i overloading is not yet clear. To provide a better insight into this mechanism, isolated rat AMs were exposed to varying concentrations of crystalline silica (particle size < 5 microns in diameter) and the fluctuation in their [Ca2+]i and cell integrity were quantitatively monitored with the fluorescent calcium probe, Fura-2 AM, and the membrane integrity indicator, propidium iodide (PI). Results from this study indicate that silica can rapidly increase [Ca2+]i in a dose-dependent manner with a characteristic transient calcium rise at low doses (< 0.1 mg/ml) and an elevated and sustained rise at high doses (> 0.1 mg/ml). Depletion of extracellular calcium [Ca2+]o markedly inhibited the [Ca2+]i rise (approximately 90%), suggesting that Ca2+ influx from extracellular source is a major mechanism for silica-induced [Ca2+]i rise. When used at low doses but sufficient to cause a transient [Ca2+]i rise, silica did not cause significant increase in cellular PI uptake during the time of study, suggesting the preservation of membrane integrity of AMs under these conditions. At high doses of silica, however, a marked increase in PI nuclear fluorescence was observed. Depletion of [Ca2+]o greatly inhibited cellular PI uptake, induced by 0.1 mg/ml or higher doses of silica. This suggests that Ca2+ influx, as a result of silica activation, is associated with cell injury. Indeed, our results further demonstrated that the low dose effect of silica on Ca2+ influx is inhibited by the Ca2+ channel blocker nifedipine. At high doses of silica (> 0.1 mg/ml), cell injury was not prevented by nifedipine or extracellular Ca2+ depletion, suggesting that other cytotoxic mechanisms, i.e., nonspecific membrane damage due to lipid peroxidation, are also responsible for the silica-induced cell injury. Silica had no significant effect on cellular ATP content during the time course of the study, indicating that the observed silica-induced [Ca2+]i rise was not due to the impairment of Ca(2+)-ATPase pumps, which restricts Ca2+ efflux. Pretreatment of the cells with cytochalasin B to block phagocytosis failed to prevent the effect of silica on [Ca2+]i rise. Taken together, these results suggest that the elevation of [Ca2+]i caused by silica is due mainly to Ca2+ influx through plasma membrane Ca2+ channels and nonspecific membrane damage (at high doses).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1993

Intraocular pressure during mechanical ventilation with different levels of positive end-expiratory pressure.

OBJECTIVE: To determine the effect of positive end-expiratory pressure (PEEP) on intraocular pressure. DESIGN: Prospective, controlled, longitudinal, dual center study. In one group, patients served as their own control. In the second group, isolated determinations of intraocular pressure were made in mechanically ventilated patients receiving PEEP. SETTING: Adult intensive care units of two university hospitals. PATIENTS: Intraocular pressures were measured serially in eight patients during the recovery phase of different clinical conditions and in 22 patients receiving mechanical ventilation with PEEP > or = 10 cm H2O for > 24 hrs. INTERVENTIONS: Group A) In eight patients, a PEEP dose-response curve was established (PEEP 0, 5, 10, 15, and 0 cm H2O every 15 mins). Intraocular pressures were measured at the end of each period. Group B) In 22 patients, measurement of intraocular pressures were done while the patients received mechanical ventilation with PEEP > or = 10 cm H2O for at least > 24 hrs. MEASUREMENTS AND MAIN RESULTS: In both groups, there was a positive correlation between the PEEP level and the central venous pressure (p < .05 in group A, and p < .03 in group B). No relationships between intraocular pressure and PEEP or central venous pressure were observed. However, there was a correlation between intraocular pressure and length of PEEP therapy (p < .03). We found ocular hypertension in only one patient (right eye intraocular pressure = 26 mm Hg; left eye intraocular pressure = 24 mm Hg). CONCLUSIONS: Short-term therapy with PEEP of < or = 15 cm H2O does not present a clinically important significant risk for intraocular pressure increase in a population with normal basal ocular tonometry. During prolonged mechanical ventilation with PEEP, increments in intraocular pressure may occur, but these increments appear to not be of a clinically relevant magnitude.

Adult↗
PubMed1993

Mechanisms of hydroxyl free radical-induced cellular injury and calcium overloading in alveolar macrophages.

Excessive production of reactive oxygen radicals by alveolar macrophages is proposed to play an important role in oxidative lung injury. A major product oxygen radical formation is the highly reactive hydroxyl radical (.OH) generated via a biologic Fenton reaction. In addition to its known ability to induce lipid peroxidation, recent studies have suggested that the .OH may exert its cytotoxic effect through the alteration of [Ca2+]i homeostasis. To test this potential mechanism as well as to investigate the relationship between .OH and Ca2+ overloading in cytotoxic injury, isolated rat alveolar macrophages were exposed to externally generated radical system, H2O2 (0.01 to 1 mM) and Fe2+ (1 mM) and their [Ca2+]i levels and cell injury were monitored using quantitative fluorescence microscopy with the aid of the specific Ca2+ indicator, Fura-2, and membrane integrity indicator, propidium iodide. Electron spin resonance measurements using the spin trap 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) confirmed the production of the .OH radical by this system. Upon the addition of the radicals, the macrophages displayed a rapid initial rise in [Ca2+]i which was followed by a slower but more pronounced [Ca2+]i elevation that reached a level 3 to 5 times higher than the basal level. This process preceded cell death as evident by nuclear propidium iodide fluorescence. Depletion of extracellular Ca2+ inhibited both the [Ca2+]i response and cell injury. Preincubation of the cells with the Ca2+ channel blocker verapamil or .OH radical scavenger mannitol similarly inhibited the [Ca2+]i rise and loss of viability. Firefly luciferase assay of cellular ATP content demonstrated that the alterations in [Ca2+]i following .OH treatment preceded the depletion of ATP.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Understanding circulatory shock. Is it hypovolemic, cardiogenic, or vasogenic?

Circulatory shock comprises a group of complex circulatory syndromes that result from a variety of conditions. It alters the function of most organ systems and has very high mortality. Identification of the type of shock (hypovolemic, cardiogenic, vasogenic, or a combination) and optimal treatment are aided by hemodynamic monitoring, including determination of preload, cardiac output, and systemic vascular resistance. Experimental studies and isolation of bioactive substances have improved understanding of the mechanisms involved in shock. Restoration of intravascular volume, cardiac contractility, and vascular tone and control of the underlying septic process when applicable are the basis of current therapy. Close monitoring and support of the affected organ systems in an intensive care environment facilitate recovery. Encouraging results with new treatments indicate improved chances for a satisfactory outcome in patients with circulatory shock.

Humans↗
PubMed1990

Neutrophil chemotactic activity in toluene diisocyanate (TDI)-induced asthma.

We quantitated serum neutrophil chemotactic activity (NCA), which is associated with mast cell or basophil activation, to determine if mast cell or basophil mediators are released during bronchoprovocation-inhalation challenge with subirritant levels of toluene diisocyanate (TDI). Four subjects with suspected TDI-induced asthma and four mite-sensitive subjects with asthma who served as a comparison group were studied. NCA was measured in a multiwell, microchemotaxis chamber. Blood samples were collected, and FEV1 measurements were performed before challenge and at regular intervals during the subsequent 24 hours. Three of four workers clinically sensitive to TDI reacted to a subirritant TDI exposure. There was no increase in NCA during placebo challenges. NCA increased in the three TDI-sensitive workers during early and late asthmatic reactions in quantities proportional to the FEV1 decline. No increase in NCA was found during TDI exposures in the TDI-negative worker. Gel filtration analysis demonstrated the main NCA fraction eluted with macromolecules of an estimated molecular weight greater than 440,000 daltons. This characteristic is compatible with neutrophil chemotactic factor of basophil or mast cell origin. The kinetics of NCA release were similar in mite- and TDI-induced asthmatic reactions. A high correlation (r = 0.97; p = 0.0006) was obtained between the percent decrease in FEV1 during early asthmatic reactions and percent increase in NCA. These observations support the hypothesis that activation of mast cells or basophils is associated with TDI-induced early and late asthmatic reaction.

Animals↗
PubMed1990

Reliability of cell counts and protein determinations in serial bronchoalveolar lavage procedures performed on healthy volunteers.

We measured the variability in volume, total cells, cell types, and proteins in the bronchoalveolar lavage fluid recovered from 10 volunteers (five smokers, five non-smokers) lavaged repeatedly over a three-year period. Thirty lavages were performed using a rigorously standardized approach. Differential counts on the cytospin preparations were performed by three independent readers and interobserver variability in the interpretation of these counts measured. Variability in interpreting the cellular counts was less in smokers than non-smokers and decreased as the number of cells of any particular type increased. Only one reader interpreting the mean percentage of cells recovered of one cell type (neutrophils) in only one smoking group, the nonsmokers, was significantly different from the other two. There was also considerable variability in bronchoalveolar lavage fluid total protein, albumin, IgG, and IgA. Expressing albumin and IgG as a percentage of total protein recovered and expressing IgA and albumin as a ratio in nonsmokers lessened the variability of these parameters. Mean and standard deviations of the cellular and protein concentrations showed that large differences in these parameters would be necessary in order to attribute these changes to changes in the underlying pulmonary status. Excessive variability in nearly all parameters in this group without recognized lung disease challenges the usefulness of this test in the clinical assessment of patients serially followed because of underlying lung disease.

Adult↗
PubMed1990

Persistence of toluene diisocyanate-induced asthma despite negligible workplace exposures.

Six polyurethane foam workers were shown to have TDI-induced asthma by specific inhalation challenge testing. All remained in the workplace in jobs with minimal TDI exposures. Mean and time-weighted average exposure concentration for the asthmatic group was 0.64 +/- 0.46 ppb, less than 5 percent of the permissible exposure limit and significantly less (p less than 0.01) than the mean TWA exposures occurring in the foam line and the finishing workers. Serial evaluation of the respiratory health of these six showed all persisted with respiratory symptoms, none had improvement in bronchial hyperresponsiveness to methacholine, and three had a greater than 15 percent decline in FEV1 on one of the days of spirometric testing over the five-year period from 1982 to 1986. Although we could not have predicted the outcome of asthma had these workers left the workplace and ceased isocyanate exposure entirely, occupational asthma persisted despite negligible ongoing TDI exposures.

Asthma↗
PubMed1989

Role of inhalation challenge testing in the diagnosis of isocyanate-induced asthma.

Results of isocyanate challenge tests performed on 63 workers referred with a diagnosis of probable isocyanate asthma between 1974 and 1988 were reviewed. Thirty (48 percent) had an acute episode of asthma with a greater than 20 percent decline in FEV1 following subirritant exposure to isocyanates. No difference in the frequency or type of respiratory complaints between isocyanate reactors and nonreactors was found. No differences in lung function results were present when comparing smoking and ex-smoking reactors and nonreactors. In never-smokers with complaints consistent with isocyanate-induced asthma, the presence of obstructive lung disease increased the likelihood that isocyanate-induced asthma was present. Bronchial responsiveness to methacholine occurred in nearly all isocyanate reactors but predicted isocyanate-induced asthma in only 68 percent of the workers. In nearly all cases of challenge-confirmed toluene diisocyanate (TDI)-induced asthma, a 15-min exposure to 20 ppb of the commercial TDI mixture (80:20 2,4:2,6) provoked asthma. Conversely, in the absence of an asthmatic response following exposure to this dose for this duration, a second exposure at this concentration for a longer time would be reasonable to confirm the absence of isocyanate-induced asthma. Among workers employed in the production of polyurethane foam and confirmed to have TDI-induced asthma by inhalation challenge to the different TDI isomers, there appeared to be increased airway reactivity to the 2,6 isomer. This may have relevance to the frequency and intensity of respiratory symptoms that workers with TDI-induced asthma develop in differing industrial settings.

Adult↗
PubMed1988

Recurrent asthma induced by toluene diisocyanate.

A worker developed toluene diisocyanate induced asthma in 1974. On reassessment, 11 years after leaving the chemical plant where toluene diisocyanate was produced, he had no respiratory symptoms and normal bronchial reactivity in response to methacholine, and showed no reaction when challenged with a subirritant concentration of toluene diisocyanate. He developed asthma within five months of returning to the workplace. Repeat challenge testing showed bronchial hyperreactivity to methacholine and to the specific sensitising agent, toluene diisocyanate. This clinical pattern could be due to underlying toluene diisocyanate sensitivity with resolution and reappearance of hyperresponsiveness to methacholine and toluene diisocyanate reactivity associated with workplace toluene diisocyanate exposure. Alternatively, this worker may have developed sensitisation to toluene diisocyanate anew.

Adult↗
PubMed1987

Cytotoxic cell function in bronchogenic carcinoma.

Biologic response modifiers (BRM) such as interleukin-2 (Il-2) and gamma-interferon (gamma IFN) can augment preexisting or initiate new cytotoxic capacity of human lymphocytes against tumor cells. Although in vivo therapy with BRM or adoptive immunotherapy with BRM-treated cells seems logical in the treatment of bronchogenic carcinoma, recent studies have shown that lymphocytes from the lung and tumor tissues of patients with bronchogenic carcinoma have defective cytotoxic function. We sought to determine if defects in lung cytotoxic cell function are primary or secondary to local tumor effects, and if peripheral blood lymphocyte populations from patients can serve as a source for BRM-stimulated cytotoxic cells. We evaluated the natural killer (NK) cell and lymphokine (Il-2) activated killer cell activity (LAK) activity of mononuclear cell populations from 11 patients with newly diagnosed bronchogenic carcinoma and three control groups. Cultured human squamous cell and adenocarcinoma cell lines proved useful in evaluating LAK activity in these studies. Levels of NK and LAK activity in patients compared favorably with both those of non-smokers in two different age ranges and with smokers. Peripheral blood cytotoxic cell function remains intact and responsive to augmentation by BRM in patients with recently diagnosed bronchogenic carcinoma. Reported defects in patient lung cell cytotoxic function appear to be local tumor-related defects not present in peripheral blood lymphocytes.

Adult↗
PubMed1987

Pulmonary immunologic features of alveolar septal amyloidosis associated with multiple myeloma.

A 74-year-old man presented with interstitial pulmonary disease which was proven to be alveolar septal amyloidosis by transbronchial biopsy. Multiple myeloma was diagnosed on the basis of monoclonal IgG-lambda protein in serum, monoclonal lambda light chains in urine, a bone marrow plasmacytosis of 22 percent, and serum IgA and IgM levels less than 100 mg/dl and 50 mg/dl, respectively. Appropriate investigations failed to show additional sites of deposition of amyloid. Analysis of fluid from bronchoalveolar lavage showed an increase in total cells recovered, a lymphocytosis with a ratio of T helper over T suppressor cells greater than that in peripheral blood, the presence of an IgG-lambda paraprotein, and an IgG/albumin ratio greater than that in serum. While plasma cells could not be identified in the recovered cell population, cultured cells from bronchoalveolar lavage fluid showed increased production of IgG. These findings provide evidence of an ongoing pulmonary immune response resulting in excess IgG-lambda protein in the pulmonary compartment, a factor which may contribute to the development of amyloidosis.

Aged↗
PubMed1986

Modulation of natural killer cell function by human alveolar macrophages.

Lymphocyte natural killer (NK) activity appears to be important in resistance against viral infection and malignancy. Since pulmonary alveolar macrophages (PAM) derived from nonsmokers suppress NK activity in vitro, we asked if PAM derived from smokers modulated NK activity in a similar fashion. Bronchoalveolar lavage cells (BLC) were obtained from healthy nonsmokers and healthy smokers by bronchoalveolar lavage. Increasing numbers of BLC were cocultured with a fixed ratio of monocyte-depleted peripheral blood lymphocytes (PBL) and Cr51-labeled K562 tumor target cells (PBL:K562, ratio 25:1; BLC:PBL ratios ranging from 0.02:1 to 1:1). Increasing numbers of BLC progressively suppressed the ability of either autologous or homologous PBL to lyse tumor targets. Smoker and nonsmoker BLC inhibited NK activity of homologous lymphocytes with similar potency. Suppression of NK activity by BLC was not reversed by the addition of indomethacin or catalase to cell cultures. Furthermore, suppression could not be reproduced by performing cytotoxicity assays in the presence of BLC culture supernatants. Lymphocytes boosted to high levels of NK activity by preincubation with alpha-interferon or interleukin-2 were still susceptible to suppression by BLC. Thus, PAM derived from smokers efficiently suppress lymphocyte NK activity, and the degree of suppression increases as the ratio of PAM to lymphocytes increases. Since smoking causes a bronchoalveolar accumulation of PAM, these inhibitory cells may result in profound local suppression of NK activity in smoker's lungs.

Adult↗
PubMed1986

Immunomodulation by bronchial lavage cells in normal individuals and patients with bronchogenic carcinoma.

The ability of bronchoalveolar lavage cells to facilitate lymphoproliferation to mitogen in a system which allows assessment of pulmonary alveolar macrophage accessory cell function was investigated. Bronchoalveolar lavage cells were obtained from healthy non-smokers and smokers and from patients undergoing diagnostic bronchoscopy. Lavaged cells were cultured with monocyte-depleted homologous blood lymphocytes obtained from healthy, young volunteers and stimulated with suboptimal (2 micrograms/ml) or optimal (20 micrograms/ml) concentrations of phytohemagglutinin. Mitogen responses of lymphocytes in all groups were related to the number of lavage cells added, increasing with 1:100 and 1:10 bronchoalveolar lavage cell to lymphocyte ratios and decreasing with 1:2 and 1:1 ratios. Lymphoproliferative responses observed in smoker and nonsmoker cultures were not different. In contrast, maximal proliferative responses of cell cultures from patients with epidermoid and small cell carcinoma were decreased compared with cultures from patients with adenocarcinoma or controls. These data show that pulmonary bronchial lavage cells from smokers and nonsmokers provide similar dose related augmentation and suppression of lymphocyte mitogenic responses. Furthermore, accessory cell function of lavage cell populations is normal in patients with adenocarcinoma, but depressed in patients with epidermoid or small cell carcinoma.

Adenocarcinoma↗
PubMed1986

Human ventilatory response to washed and unwashed cottons from different growing areas.

Thirty volunteer subjects were exposed to controlled amounts of respirable dust generated by the carding of cotton in an experimental cardroom. Eighteen exposures each lasting six hours were performed while carding unwashed and washed cottons from the three major growing regions of the United States. Elutriated dust was analysed gravimetrically and was comparable (0.59 mg/m3 +/- 0.04) for all exposures. Spirometry was recorded before and after each exposure. California cotton resulted in a significantly smaller fall in FEV1 than cotton of the same grade from Texas or Mississippi. All washed cottons resulted in reduced declines when compared with unwashed cottons. For 17 subjects breathing zone personal total dust samples were analysed for airborne endotoxin and compared with the individual's pulmonary function response. A significant correlation between endotoxin exposure and acute decrease in FEV1 was seen. The effect on FEV1 per nanogram of airborne endotoxin was greater for Mississippi cotton than for cotton from the other regions. Airborne endotoxin appears to be an important determinant of acute pulmonary effects of cotton dust. Water washing of cotton results in reduced airborne endotoxin and less bronchoconstriction.

Byssinosis↗
PubMed1986

Modification of the methacholine inhalation test and its epidemiologic use in polyurethane workers.

The dosimeter method of administering doubling cumulative doses of methacholine to measure bronchial responsiveness was standardized to control for the effects of a number of potential influencing variables. The aerodynamic mass median diameter of the challenge aerosol produced from a DeVilbiss 646 nebulizer proved to be 1.2 mu, and the mean output per inhalation 8.9 microliters. Each challenge dose comprised 5 inhalations. Cumulative doses ranged from 0.3 methacholine inhalation units (1 unit = 1 inhalation of aerosol from a 1-mg/ml solution of methacholine, i.e., 8.9 micrograms methacholine) to a possible 640 units, the maximum that was considered reasonable to avoid the risk of unacceptable systemic effects. Responsiveness was expressed as the dose provoking a 20% decline (PD20) in FEV1. Modifications in this full protocol were introduced to facilitate epidemiologic investigations. Physician assessments coupled with baseline measurements of ventilatory function allowed starting at higher dosages for persons with low probability of hyperresponsiveness, thereby shortening the time required for testing to an average of 38 min. In a validation study of 20 persons using both the full and modified protocols, no significant differences were detected between measured PD20 values (geometric means Full versus Modified, 14.83 versus 14.88; r = 0.99). The modified protocol was used to measure bronchial responsiveness in 254 workers exposed to toluene diisocyanate. It proved to be safe and acceptable. Sixty-four workers (25.2%) were found to be reactors. The frequency distribution of the PD20 values exhibited a steadily increasing trend, consistent with a unimodal distribution.

Adult↗
PubMed1986

Absence of hyperresponsiveness to methacholine in a worker with methylene diphenyl diisocyanate (MDI)-induced asthma.

A 29-year-old man had a persuasive history of respiratory illness following exposures to methylene diphenyl diisocyanate (MDI). He was evaluated by measuring bronchial reactivity to methacholine, both before and after controlled laboratory exposures to MDI. Despite evidence of progressive declines in FEV1 with increasing (but subirritant) doses of MDI on three consecutive days, there was no bronchial hyperresponsiveness to methacholine, before or after MDI challenge. We conclude that the absence of nonspecific bronchial hyperresponsiveness does not exclude the possibility of isocyanate asthma. In the face of a compelling history, a negative result of methacholine challenge should not deter observation or laboratory testing for specific respiratory allergy to these chemicals.

Adult↗