Biomedical subjects

D N Weissman

Publications and source records attributed to D N Weissman.

At least 19 recordsLinked to original sources

PubMed2005

Tuberculosis mortality by industry in the United States, 1990-1999.

OBJECTIVE: To identify occupations and industries with elevated respiratory tuberculosis (TB) mortality in the United States for the period 1990-1999, we used National Center for Health Statistics multiple-cause-of-death data, restricted to certain states for which information on decedents' usual industry and occupational information was available and limited to US residents aged > or =15 years. DESIGN: A total of 7686 deaths between 1990 and 1999 were attributed to respiratory TB. Proportionate mortality ratios (PMRs), adjusted for age, sex, and race, were calculated from US census occupation and industry classifications. RESULTS: Industries and occupations involving potential contact with infected cases (e.g., health care workers), those with silica exposure and silicosis (e.g., mining and construction), and those associated with low socioeconomic status had significantly elevated TB mortality. CONCLUSIONS: Overall, the pattern of findings echoes that described in various prior reports, which indicates that the potential for exposure and disease development still persists among certain worker groups. The findings should be useful in guiding occupationally targeted TB prevention programs.

Female↗

PubMed2001

Respiratory symptoms among crab processing workers in Alaska: epidemiological and environmental assessment.

BACKGROUND: Crab processing workers may develop respiratory symptoms and specific IgE responses, but the risk factors have not been fully described. METHODS: In 1998, 107 workers at a crab processing facility completed a survey both at the beginning and end of the processing season. The surveys included standardized symptom questionnaires, spirometry, and serological testing, as well as measurement of workplace airborne crab allergens and microscopic analysis of aerosolized materials. RESULTS: Over the crab processing season, asthma-like symptoms developed in 26% of study participants and bronchitic symptoms in 19%. Only 9% of those with new asthma-like symptoms were IgE-sensitized to crab at the end of the season. Among the crab processing jobs, butchering and degilling workers had the highest incidence of respiratory symptoms. CONCLUSIONS: Both personal and process-related factors appear to affect the development of respiratory symptoms in crab processing workers. In this study, crab specific IgE was not detected in most of the workers with new symptoms. Published 2001 Wiley-Liss, Inc.

Adolescent↗

PubMed2001

Immunoglobulin responses to experimental silicosis.

Silicosis is a crippling fibrotic lung disease induced by inhalation of crystalline silica. One feature of silicosis is systemic and pulmonary immune dysfunction characterized in part by elevations in serum and bronchoalveolar lavage (BAL) immunoglobulins. A major specific aim of the current report was to demonstrate that an experimental model of silicosis previously well characterized for the development of pulmonary inflammation and fibrosis would also exhibit increased levels of serum and BAL IgG and IgM similar to those of human silicosis. We also sought to document the anatomic compartments responsible for these immunoglobulin responses. To address these specific aims, we compared levels of IgG and IgM in serum and BAL from rats with experimental silicosis induced by inhalation of silica with levels of these immunoglobulins in titanium dioxide (TiO(2))- and sham (air)-exposed controls. The ability of mononuclear cell populations from lung, lung-associated lymph node, and spleen to produce IgG and IgM ex vivo were also compared. We found that experimental silicosis was associated with elevated IgG and IgM levels in blood and BAL relative to the control groups. Our findings also suggested that draining lung-associated lymph nodes (LALN) were the most important sites for increased IgG and IgM production in experimental silicosis, with lungs contributing to a lesser degree. Increased production in the LALN appeared related to marked expansion in total numbers, but not relative proportion, of B lymphocytes.

Administration, Inhalation↗

PubMed2001

Effect of age on respiratory defense mechanisms: pulmonary bacterial clearance in Fischer 344 rats after intratracheal instillation of Listeria monocytogenes.

STUDY OBJECTIVES: To examine the lung defense mechanisms of both young and aged rats before and after pulmonary challenge with a bacterial pathogen. DESIGN: Male Fischer 344 rats, either 2.5 months or 20 months of age, were intratracheally inoculated with 5 x 10(3), 5 x 10(4), or 5 x 10(5) Listeria monocytogenes, and the effects on mortality, lung inflammation, pulmonary bacterial clearance, alveolar macrophage (AM) function, and T-lymphocyte characterization were determined. MEASUREMENTS AND RESULTS: In noninfected control animals, the older rats had lower numbers of AMs on lavage and a lower percentage of total T, CD4+, and CD8+ cells. No difference was observed between noninfected young and old rats in AM function, assessing both chemiluminescence and nitric oxide (NO) production. After bacterial challenge, aged rats exhibited an increase in mortality, pulmonary infection, and edema, and lung lesions, which were more extensive than those observed in the younger rats. Interestingly, AM chemiluminescence was enhanced, while AM NO, a highly important antibacterial defense product, was abrogated in the aged rats as compared to the young rats. CONCLUSIONS: This study demonstrated that advanced age is associated with alterations in lung defense mechanisms and increased susceptibility to pulmonary bacterial infection marked by elevated mortality, slowed pulmonary bacterial clearance, and altered AM function, specifically a decrease in NO production. These observations are indicative of reduced pulmonary defense function in an older population of rats.

Aging↗

PubMed2001

IgG subclass responses in experimental silicosis.

Silicosis is a crippling fibrotic lung disease induced by inhaling crystalline silica. In addition to fibrosis, silica inhalation by humans is associated with a number of immunological effects including increased levels of serum immunoglobulins (in particular IgG), increased prevalence of autoantibodies, and autoimmune disease. Recent studies using rodent models have shown that experimental silicosis is associated with a T-helper (TH)1 pattern of T-cell activation in the lungs and lung-associated lymph nodes after silica inhalation, which are also the sites of increased IgG production. We therefore hypothesized that the subclass distribution of IgG production occurring in experimental silicosis would suggest TH1 activation as the primary stimulus for IgG production. Using an ELISPOT assay, we found increased IgG-secreting spot-forming cells of all IgG subclasses in lung-associated lymph nodes taken from silica-exposed rats 3 to 4 months after aerosol exposure to silica. Neither TH1- nor TH2-dependent IgG subclass-secreting cells were selectively enhanced. Our findings suggest that TH1 activation alone does not account for increased production of IgG in experimental silicosis.

Administration, Inhalation↗

PubMed2000

[The effects of smoking on pulmonary IgA and immune response to antigen in young smokers].

OBJECTIVE: To evaluate the influence of smoking on pulmonary immune function. METHODS: Twelve healthy volunteers, of them 5 smokers and another 7 nonsmokers, underwent right middle lobe bronchoalveolar lavage (BAL) and transbronchial instillation of KLH into lingula. Dimeric and monomeric IgA, albumin and cellular differential count in BALF were measured. Serum anti-KLH IgA was tested at various days after instillation of antigen. RESULTS: The level of monomeric IgA, counts of neutrophils and pulmonary macrophages in BALF of smokers were significantly higher than nonsmokers. Positive correlations were found between mIgA, and albumin and neutrophils counts. Serum anti-KLH IgA level in smokers increased slower and decreased earlier than in nonsmokers. CONCLUSIONS: Smoking causes inflammatory responses in lung and injures pulmonary immune response to antigen in young smokers.

Adult↗

PubMed1997

Antisense inhibition of silica-induced tumor necrosis factor in alveolar macrophages.

Tumor necrosis factor-alpha (TNFalpha) has been shown to play an important role in the pathogenesis of silicotic fibrosis. In this study, antisense oligonucleotides targeted to TNFalpha mRNA were used to inhibit silica-induced TNFalpha gene expression in alveolar macrophages. To achieve macrophage-specific oligonucleotide delivery, a molecular conjugate consisting of mannosylated polylysine that exploits endocytosis via the macrophage mannose receptor was used. Complexes were formed between the mannosylated polylysine and oligonucleotides and added to the cells in the presence of silica. Enzyme-linked immunoadsorbent assay showed that the complex consisting of the conjugate and antisense oligomer effectively inhibited TNFalpha production, whereas the oligomer alone had much less effect. Reverse transcriptase-polymerase chain reaction analysis revealed that the reduction in TNFalpha secretion was associated with specific ablation of targeted TNFalpha mRNA. The conjugate alone or conjugate complexed with inverted or sense sequence oligonucleotide had no effect. The promoting effect of the conjugate on antisense activity was shown to be due to enhanced cellular uptake of the oligomer via mannose receptor-mediated endocytosis. Cells lacking mannose receptors showed no susceptibility to the conjugate treatment. These results indicate that effective and selective inhibition of macrophage TNFalpha expression can be achieved using the antisense mannosylated polylysine system.

Animals↗

PubMed1996

Reduction of lung dust burden in pneumoconiosis by whole-lung lavage.

Pneumoconioses are characterized as irreversible, progressive respiratory diseases. No effective therapy exists to prevent progression of these diseases. Whole-lung lavage (WLL) might limit the rate of disease progression through the removal of dust, inflammatory cells, and cytokines. We performed WLL on a 54-year-old underground miner employed as a motorman and roof bolter and a 55-year-old driller at a surface coal mine. Both demonstrated normal lung function and chest radiographs showing ILO profusion category 2 nodular interstitial changes. From Subject 1, we recovered 5.24 x 10(8) cells (90% macrophages) from the right lung and 3.45 x 10(8) cells (94% macrophages) from the left lung. WLL removed 1.82 g of mineral dust (non-coal) on the right and 1.64 g on the left. From Subject 2, we recovered 7.49 x 10(8) cells (46% macrophages) from the right and 9.78 x 10(8) cells (69% macrophages) from the left lung. WLL removed 0.40 g of mineral dust on the right and 0.53 g on the left. Proinflammatory cytokines, growth factors, and cellular enzymes were also recovered. In cases of pneumoconiosis, WLL is capable of removing relatively large quantities of dust, cells, and soluble materials from the lungs. Only long-term follow-ups of individuals with progressive dust-induced disease who receive WLL therapy in the context of a clinical trial will provide information regarding the importance of removing mineral dust and inflammatory cells from the lung.

Bronchoalveolar Lavage↗

PubMed1996

Bronchoprovocation tests in the diagnosis of isocyanate-induced asthma.

Over the past 25 years, investigators have continued to improve on the approach to providing nonirritant exposures for the accurate diagnosis of isocyanate-induced asthma. Although the technology used in testing has become more sophisticated and may be fairly considered the domain of the bioengineer, the chemist, and the industrial hygienist, the requirements of the physician have remained unchanged. The physician must observe the level of exposure closely and monitor the worker's symptoms and lung function. Direct physician involvement in the testing procedure remains critical to the worker's safety and for the accurate diagnosis of isocyanate-induced asthma.

Asthma↗

PubMed1994

Intrapulmonary antigen deposition in the human lung: local responses.

We hypothesized that, as in animal models, localized deposition of antigen into the human lung would induce local inflammatory and immune responses in antigen-exposed sites. To test this hypothesis, segmental instillation of a well-characterized, highly immunogenic, soluble antigen, keyhole limpet hemocyanin (KLH) was performed in 10 healthy, nonsmoking volunteers. Ten to fifteen days after instillation, bronchoalveolar lavage (BAL) was performed in immunized segments (IS) and contralateral control segments (CS) and local responses to antigen instillation were assessed by comparing IS and CS BAL. Greater albumin concentrations and cell recoveries were found in IS than in CS BAL, suggesting local inflammation. Although total numbers of each cell type were increased, relative proportions of alveolar macrophages, lymphocytes, and neutrophils were similar in IS and CS BAL. CD4/CD8 ratios in IS BAL samples were greater than those in CS samples, because of higher numbers of CD4+ lymphocytes in IS than in CS BAL but similar numbers of CD8+ lymphocytes. Anti-KLH IgG and IgA concentrations were greater in IS than in CS BAL. However, anti-KLH IgG/albumin ratios were similar in IS BAL and serum, suggesting that anti-KLH IgG had reached IS by passive transudation from the circulation. In contrast, anti-KLH IgA/albumin concentrations were greater in IS BAL than in serum, suggesting local production, and/or active transport of serum-derived anti-KLH IgA into the IS. Fractionation of serum and IS BAL on sucrose gradients demonstrated that anti-KLH IgA activity was largely associated with 11S polymeric IgA in both locations.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗

PubMed1992

Primary immunization in the canine lung. Soluble antigen induces a localized response.

Primary immunization of the dog by intralobar instillation of particulate antigen induces an intense, localized pulmonary antibody response. In contrast, although soluble antigen can also induce local antibody responses after repeated deposition in the canine respiratory tract, its ability to induce local responses after primary immunization has not been well characterized. To document such responses, we immunized five beagle dogs using a bronchoscope to instill 10 mg keyhole limpet hemocyanin (KLH) into a single lung lobe (immunized) and saline into a contralateral lung lobe (control). Over the next 3 wk, we monitored specific immune responses in blood and bronchoalveolar lavage (BAL) fluids obtained from the immunized and control lung lobes. Primary intrapulmonary immunization of dogs with KLH resulted in anti-KLH antibody responses both in blood and in immunized and control BAL fluids. However, immunoglobulin class-specific expression of response differed between the immunized and control lung lobes. Specific IgM and IgA responses were significantly greater in the immunized lobes. In contrast, specific IgG, and cells producing specific IgG, were quantitatively similar in lavage fluids derived from immunized and control lung lobes. These studies demonstrate that primary immunization of the dog by intralobar instillation of soluble antigen stimulates a local IgM and IgA response and an IgG response that distributes to both immunized and unimmunized lung. This pattern of immunoglobulin class-specific pulmonary antibody response has the potential to importantly influence regional responses to intrapulmonary antigen.

Animals↗

PubMed1991

Comparative morphology and morphometry of alveolar macrophages from six species.

Pulmonary alveolar macrophages (PAM) were collected from normal, healthy mice, rats, dogs, cynomolgus monkeys, chimpanzees, and humans and evaluated for morphologic and morphometric characteristics. The PAM of mice, rats, and dogs were morphologically similar and had statistically similar frequency distributions for size. The cell size distribution for these three species was relatively homogeneous. The PAM of nonhuman primates and humans were morphologically heterogenous with sometimes prominent cytoplasmic vacuolation, irregular cell outlines, and increased numbers of multinucleated cells as compared to the PAM of rodents and dogs. The mean size of human PAM was statistically greater than that for all other species evaluated, including nonhuman primates. These data indicate that significant differences in PAM morphology and size exist among species.

Animals↗

PubMed1991

Long-term maintenance of localized antibody responses in the lung.

Immune memory cells for antibody production in the lung respond to antigen challenges, providing an important pulmonary defence. However, studies reported here suggested that long-term antibody production in the lung might also be important in pulmonary immune memory. After localized lung immunization and challenges, antibody production of specific IgG and IgA continued in the immunized lung lobes of dogs for months after the last antigen exposure. In addition, the evaluation of lung immunity in dogs immunized and challenged 3 years or 5 years previously (without additional antigen challenge) showed significantly higher levels of specific antibody in lavage fluid from the lung lobe exposed to antigen than in lavage fluids from control lung lobes. Cells from blood or from control lung lobes did not produce significant levels of specific antibody in vitro, whereas cells lavaged from the immunized lung lobes were producing specific antibody. Therefore, long-term antibody production by cells in lung lobes exposed to antigen probably contributed to antibody levels in serum and unexposed lung lobes. Traditionally, lymphoid tissues are believed to be responsible for long-term antibody production. However, antibody production in the lung for years without repeated antigen exposure suggested that other tissues might also be important in long-term antibody production. Maintenance of localized antibody production in the lung would be an important pulmonary defence against infectious agents, but might also play a key role in hypersensitivity lung diseases.

Animals↗

PubMed1990

Murine lung immunity to a soluble antigen.

Although it is known that soluble antigen is immunogenic when deposited in the respiratory tract, less is known about lung immunity to soluble antigen than is known about lung immunity to particulate antigen. To test the hypothesis that soluble antigen triggers antigen-specific immunity in the respiratory tract in a fashion similar to that reported for particulate antigen, we examined the development of local and systemic immunity in C57BL/6 mice after intratracheal (i.t.) instillation of a soluble, large molecular weight protein neoantigen, keyhole limpet hemocyanin (KLH). Specific anti-KLH IgG and IgM first appeared in the sera of mice on day 7 after primary immunization by i.t. instillation of KLH, with specific serum antibody concentrations remaining elevated at day 11. Cell populations prepared from lung-associated lymph nodes of immunized mice released specific anti-KLH IgG and IgM in vitro; peak levels were obtained from cells isolated 7 days after antigen instillation, with levels of specific antibody released by cells isolated on days 9 and 11 decreasing markedly. Cultured spleen cells obtained from mice after primary immunization released only low levels of specific IgM, and no specific IgG. No specific antibody was released by cell populations derived from the lungs of animals undergoing primary immunization. When presensitized mice were given an i.t. challenge with KLH, responses differed markedly from those following primary immunization. Lung-associated lymph node cell populations from challenged mice released greater amounts of specific antibody earlier than did cell populations from mice undergoing primary immunization.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1987

Antigenic/allergenic analysis of basidiomycete cap, mycelia, and spore extracts.

Since airborne basidiospores may be important inducers of respiratory allergy, extracts of spores, caps and mycelia from Pleurotus ostreatus were studied by immunologic techniques. Crossed immunoelectrophoresis of the Pleurotus spore extract showed it to be a complex mixture containing at least 27 precipitating antigens. Crossed-line immunoelectrophoresis comparing Pleurotus spore extract with extracts of Pleurotus cap or mycelia demonstrated both common antigens and antigens unique to the spore extract. Inhibition of Pleurotus spore RAST by extracts of Pleurotus spore, cap, and mycelia suggested that these extracts contained common allergenic components. However, wheal and flare skin reactivity of allergic patients to extracts of P. ostreatus or Cantharellus cibarius demonstrated little correlation between reactivity to cap and spores. These results demonstrate that basidiomycete spore extracts are the best diagnostic reagents to use in clinical studies, although cap and mycelia extracts may provide useful material for further allergen analysis.

Allergens↗

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↗

PubMed1985

Pulmonary manifestations of the rheumatic diseases.

The collagen vascular diseases represent a heterogeneous group of multisystem disorders with a wide range of clinicopathologic features. Although these diseases represent distinct clinical entities, a great deal of overlap exists between them. For example, the diffuse interstitial fibrosis of SLE, RA, DM-PM, PSS, and MCTD are indistinguishable clinically, radiographically, and histologically. Conversely, the pulmonary manifestations of the various vasculitides all differ significantly from each other in their clinicopathologic presentation, as well as in their response to therapy. For diagnostic purposes, histologic evidence will usually be required for the pulmonary manifestations of the rheumatic diseases. Therapy must then be individualized for each of these entities, as the protocol and response are variable.

Arthritis, Rheumatoid↗