Thermoelectric current in a graphene Cooper pair splitter.

Generation of electric voltage in a conductor by applying a temperature gradient is a fundamental phenomenon called the Seebeck effect. This effect and its inverse is widely exploited in diverse applications ranging from thermoelectric power generators to temperature sensing. Recently, a possibility of thermoelectricity arising from the interplay of the non-local Cooper pair splitting and the elastic co-tunneling in the hybrid normal metal-superconductor-normal metal structures was predicted. Here, we report the observation of the non-local Seebeck effect in a graphene-based Cooper pair splitting device comprising two quantum dots connected to an aluminum superconductor and present a theoretical description of this phenomenon. The observed non-local Seebeck effect offers an efficient tool for producing entangled electrons.

Bolometer operating at the threshold for circuit quantum electrodynamics.

Radiation sensors based on the heating effect of absorbed radiation are typically simple to operate and flexible in terms of input frequency, so they are widely used in gas detection1, security2, terahertz imaging3, astrophysical observations4 and medical applications5. Several important applications are currently emerging from quantum technology and especially from electrical circuits that behave quantum mechanically, that is, circuit quantum electrodynamics6. This field has given rise to single-photon microwave detectors7-9 and a quantum computer that is superior to classical supercomputers for certain tasks10. Thermal sensors hold potential for enhancing such devices because they do not add quantum noise and they are smaller, simpler and consume about six orders of magnitude less power than the frequently used travelling-wave parametric amplifiers11. However, despite great progress in the speed12 and noise levels13 of thermal sensors, no bolometer has previously met the threshold for circuit quantum electrodynamics, which lies at a time constant of a few hundred nanoseconds and a simultaneous energy resolution of the order of 10h gigahertz (where h is the Planck constant). Here we experimentally demonstrate a bolometer that operates at this threshold, with a noise-equivalent power of 30 zeptowatts per square-root hertz, comparable to the lowest value reported so far13, at a thermal time constant two orders of magnitude shorter, at 500 nanoseconds. Both of these values are measured directly on the same device, giving an accurate estimation of 30h gigahertz for the calorimetric energy resolution. These improvements stem from the use of a graphene monolayer with extremely low specific heat14 as the active material. The minimum observed time constant of 200 nanoseconds is well below the dephasing times of roughly 100 microseconds reported for superconducting qubits15 and matches the timescales of currently used readout schemes16,17, thus enabling circuit quantum electrodynamics applications for bolometers.

Production and purification of lentiviral vectors generated in 293T suspension cells with baculoviral vectors.

Lentivirus can be engineered to be a highly potent vector for gene therapy applications. However, generation of clinical grade vectors in enough quantities for therapeutic use is still troublesome and limits the preclinical and clinical experiments. As a first step to solve this unmet need we recently introduced a baculovirus-based production system for lentiviral vector (LV) production using adherent cells. Herein, we have adapted and optimized the production of these vectors to a suspension cell culture system using recombinant baculoviruses delivering all elements required for a safe latest generation LV preparation. High-titer LV stocks were achieved in 293T cells grown in suspension. Produced viruses were accurately characterized and the functionality was also tested in vivo. Produced viruses were compared with viruses produced by calcium phosphate transfection method in adherent cells and polyethylenimine transfection method in suspension cells. Furthermore, a scalable and cost-effective capture purification step was developed based on a diethylaminoethyl monolithic column capable of removing most of the baculoviruses from the LV pool with 65% recovery.

Matrix metalloproteinases-7, -8, -9 and TIMP-1 in the follow-up of diisocyanate-induced asthma.

BACKGROUND: Diisocyanate-induced asthma (DIA) is known to be associated with poor prognosis. We wished to clarify if matrix metalloproteinases (MMP)-7, -8 or -9 or tissue inhibitor of matrix metalloproteinases (TIMP-1) are associated with the functional or inflammatory outcome in DIA patients. METHODS: This is a longitudinal study where 17 patients with DIA diagnosed by a specific challenge test to diisocyanates were monitored. Exposure to diisocyanates was terminated seven (mean) months before the challenge test. The studies included spirometry, histamine challenge test and bronchoscopy. MMP-7, MMP-8, TIMP-1 [Enzyme-linked immunosorbent assay (ELISA)- and immunofluorometric assay-methods], MMP-9 (ELISA and zymography), interferon-gamma, tumour necrosis factor-alpha, interleukin-6, -8, -15, -17, CXCL-5/ENA-78, monocyte chemoattractant protein-1 and macrophage inhibitory factor (MIF) (ELISA) were assayed from bronchoalveolar lavage (BAL) fluid. Inhaled steroid therapy was initiated after the examinations, which were repeated at 6 months and at 3 years during the treatment. The results were compared with those of 15 healthy controls. RESULTS: Inhaled steroid medication increased BAL levels of MMP-9 and MMP-9/TIMP-1 and decreased MMP-7 and MMP-7/TIMP-1. The increase in MMP-9 levels was associated with a decline in the TH-2 type inflammation. CONCLUSIONS: Our data suggest that reduced TH-2 type inflammation in DIA after inhaled steroid medication is reflected as elevated MMP-9 and MMP-9/TIMP-1 levels in BAL. MIF may be the inducer of MMP-9. This might point to some protective role for MMP-9 in DIA.

Inflammation and functional outcome in diisocyanate-induced asthma after cessation of exposure.

BACKGROUND: The clinical outcome of diisocyanate-induced asthma has been found to be poor despite cessation of exposure. Our aim was to study the outcome of diisocyanate-induced asthma after initiation of inhaled steroid treatment at a mean period of 7 months (range 2-60 months) after cessation of exposure by following up lung function and bronchial inflammation. METHODS: Bronchoscopy was performed on 17 patients 2 days after a positive inhalation challenge test, after which budesonide 1600 mug a day was started. Bronchoscopy, spirometry, and histamine challenge tests were repeated at 6 months and on average 3 years. The results were also compared with those obtained from 15 healthy control subjects. RESULTS: Nonspecific bronchial hyperreactivity diminished significantly (P = 0.006); however, forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) values decreased, with a median yearly reduction of FEV1 of 79 ml. The count of mast cells in bronchial mucosa decreased (P = 0.012) and that of macrophages increased (P = 0.001). Interleukin-4 level in mucosa was during the first year significantly higher than in controls but its level decreased in the follow-up. Interleukin-6, interleukin-15, and tumour necrosis factor alpha messenger-RNA levels were significantly higher in hyperreactive patients than in nonhyperreactive patients at the end of the follow-up. CONCLUSION: Our results indicate that inflammation may persist in diisocyanate-induced asthma despite inhaled steroid medication. However, TH2-type inflammation diminished. Persistent nonspecific bronchial hyperreactivity was associated with proinflammatory acting cytokines produced mainly by macrophages. Considering the poor prognosis of the disease the findings could be utilized to develop the follow-up and treatment of diisocyanate-induced asthma.

Airway inflammation and basement membrane tenascin in newly diagnosed atopic and nonatopic asthma.

Previous studies have shown both similar and distinct inflammatory changes in atopic and nonatopic asthma. This study was set to investigate the bronchial inflammatory cell infiltrate and subepithelial basement membrane (BM) tenascin deposition in subjects with newly diagnosed asthma and bronchial hyperresponsiveness (BHR). Seventy-nine asthmatic subjects (age 18-60 years) were recruited and 58 were atopic according to skin prick testing. The patients recorded asthma symptoms and peak flow measurements for 14 days. Lung function and BHR were measured by spirometry and histamine challenge. Serum eosinophil cationic protein (ECP) and blood eosinophils were assessed. Fiberoptic bronchoscopy was performed to obtain bronchial biopsies. Serum ECP was higher in the atopic group but eosinophil counts did not differ. There were no differences in inflammatory cells studied (activated eosinophils, T-lymphocytes, mast cells or macrophages) between nonatopic and atopic subjects. BM tenascin layer was significantly thicker in atopic compared with nonatopic subjects (7.6 vs 6.3 microm, P = 0.007). The thickness of tenascin correlated with eosinophil, T-lymphocyte, and macrophage counts, as well as with IL-4-positive cell counts and the correlation was seen only in atopic asthmatics. These findings suggest that inflammatory cells may have a regulatory role in tenascin expression in atopic asthma.

Biopsy markers of airway inflammation and remodelling.

Bronchial inflammation is a consistent feature of asthma and its chronicity probably determines disease progression. Clinical evaluation of drugs with potential disease-modifying activity requires measurement of their effects on the inflammatory and remodelling process using a variety of techniques including bronchial biopsy, and analysis of sputum, bronchoalveolar lavage, blood, urine and exhaled air. Markers of the key components of the inflammatory process, such as the number and activation of T-cells. the number of mast cells, cytokine and chemokine release or gene expression, and eosinophil and neutrophil recruitment, can be determined in biopsy samples. Biopsies also allow assessment of the integrity and structure of the airway epithelium, the thickness of the reticular basement membrane and the numbers and ultrastructure of contractile cells. These and other markers may allow differentiation between subtypes of asthma patient according to atopic status and will help to distinguish asthma from chronic obstructive pulmonary disease. Airway remodelling may be a consequence of chronic bronchial inflammation and is a characteristic of chronic asthma, particularly in severe asthma and when there is progressive decline in lung function. There are changes in the surface epithelium, reticular basement membrane, bronchial smooth muscle, blood vessels and mucous glands. Reliable markers of remodelling need to be identified to improve our ability to evaluate chronic asthma therapy.

Endothelial sulfated sialyl Lewis x glycans, putative L-selectin ligands, are preferentially expressed in bronchial asthma but not in other chronic inflammatory lung diseases.

Lymphocyte infiltrate is a hallmark of inflammatory responses. We have previously shown that de novo-induced endothelial sialyl Lewis x (sLex) expression guides lymphocytes in an L-selectin-dependent manner to sites of acute organ transplant rejections. In this research, we have analyzed five groups of chronic lung inflammations to determine the presence of properly glycosylated, i.e., sulfated, sLex-decorated, L-selectin ligands. Two anti-sLex (2F3 and HECA-452) and one anti-6- and/or 6'-sulfated and/or 6,6'-bisulfated (MECA-79) monoclonal antibodies (mAbs) were used. The control lung specimens did not express L-selectin ligands on endothelium. In contrast, the endothelial staining intensity and the number of positive peribronchial venules and capillaries with mAbs 2F3, HECA-452, and MECA-79 were significantly greater in bronchial biopsies from patients with asthma compared with normal specimens (P<0.003). However, no significant increase of peribronchial endothelial reactivity with these antibodies was observed in adult respiratory distress syndrome, chronic bronchitis, fibrosing alveolitis, and granulomatous inflammation compared with controls. These data suggest that sulfated sLex glycans, acting putatively as ligands for L-selectin, could be instrumental in lymphocyte extravasation into human peribronchial lung tissue during asthma, but not so important in several other inflammatory lung diseases.

Placebo-controlled study of inhaled budesonide on indices of airway inflammation in bronchoalveolar lavage fluid and bronchial biopsies in cross-country skiers.

BACKGROUND: Asthma-like symptoms, methacholine hyperresponsiveness, use of inhaled steroids, airway inflammation, and increased tenascin expression in the reticular basement membrane have been reported in competitive cross-country skiers. OBJECTIVE: To investigate the effect of inhaled budesonide, 400 mug twice daily, on indices of airway inflammation in 'ski asthma', defined as asthma-like symptoms within the previous year and bronchial hyperresponsiveness to methacholine. METHODS: A randomised double-blind placebo-controlled parallel-group bronchial biopsy and bronchoalveolar lavage (BAL) study of 25 (19 male) competitive cross-country skiers (mean age 18 (16-20) years for a mean (range) treatment period of 22 (10-32) weeks over the competitive season. RESULTS: No changes were seen regarding cellular inflammation in the bronchial mucosa or tenascin expression. In the BAL fluid, both groups had a significant decrease in activated T-suppressor (CD8) lymphocytes and an increase in macrophages, with no differences across the groups. Within the budesonide group, there was a decrease in IL2 receptor-activated T-helper lymphocytes and an improvement in FEV(1). Asthma-like symptoms were unchanged in 17 (68%) skiers. Methacholine provocation test was negative in 15 subjects, and remained positive in 5 subjects in each group. The improvement in bronchial responsiveness occurred in both groups and was not accompanied by a decrease in cellular inflammation. CONCLUSIONS: We were unable to show any clear beneficial effect of budesonide in 'ski asthma'. As changes in training intensity probably accounted for the spontaneous improvement in bronchial responsiveness, more attention should be directed at reducing environmental stress to the airways than at attempting pharmacological modulation of induced inflammatory changes.

In vitro determination of carcinogenicity of sixty-four compounds using a bovine papillomavirus DNA-carrying C3H/10T(1/2) cell line.

A new in vitro test for predicting rodent carcinogenicity is evaluated against a testing database of 64 chemicals including both genotoxic and nongenotoxic carcinogens and carcinogens that normally require addition of an S-9 microsomal fraction for detection in the bacterial mutagenicity assay. The assay uses focus formation in a stable, bovine papillomavirus type 1 (BPV-1) DNA carrying C3H/10T(1/2) mouse embryo fibroblast cell line (T1) that does not require transfection, infection with virus, isolation of primary cells from animals, or addition of a microsomal fraction. Of a total database of 64 compounds, 92% of the carcinogens, promoters, or noncarcinogens were correctly predicted. Based on previously reported results, the test of bacterial mutagenicity would have correctly predicted 58% of carcinogens, promoters or noncarcinogens and the Syrian hamster embryo test would have correctly predicted 87% of carcinogens, promoters, or noncarcinogens of this database. Of carcinogens that normally require addition of an S-9 fraction, T1 cells correctly predicted rodent carcinogenicity of polyaromatic hydrocarbons, aflatoxins, azo-compounds, nitrosamines, and hydrazine without the addition of an S-9 fraction. Of nongenotoxic carcinogens, T1 cells correctly predicted diethylstilbestroel, diethylhexylphthalate, acetamides, alkyl halides, ethyl carbamate, and phorbol ester tumour promoters.

Evidence of airway inflammation and remodeling in ski athletes with and without bronchial hyperresponsiveness to methacholine.

Asthma-like symptoms, methacholine hyperresponsiveness, and use of asthma medication are prevalent in elite cross-country skiers. We quantitated mucosal inflammatory cell infiltration and tenascin expression in the subepithelial basement membrane in endobronchial biopsy specimens of the proximal airways from 40 elite, competitive skiers (mean: 17.5; range: 16 to 20 yr) without a diagnosis of asthma, in 12 subjects with mild asthma, and in 12 healthy controls, through immunohistochemistry and indirect immunofluorescence, respectively. All of the subjects were nonsmokers. T-lymphocyte, macrophage, and eosinophil counts were, respectively, greater by 43-fold (p < 0.001), 26-fold (p < 0.001), and twofold (p < 0.001) in skiers, and by 70-fold (p < 0.001), 63-fold (p < 0.001), and eightfold (p < 0.001) in asthmatic subjects than in controls. In skiers, neutrophil counts were more than twofold greater than in asthmatic subjects, and mast cell counts were not significantly different than in controls. Tenascin expression (as measured through the thickness of the tenascin-specific immunoreactivity band in the basement membrane) was increased in skiers (median: 6.7 microm; interquartile range [IQR]: 5.3 to 8.5 microm, p < 0.001) and asthmatic subjects (mean: 8.8 microm; IQR: 7.2 to 10.8 microm, p < 0. 001) compared with controls (mean: 0.8 microm; IQR: 0 to 3.1 microm) and did not correlate with inflammatory cell counts. Inflammatory changes were present irrespective of asthmalike symptoms, hyperresponsiveness, or atopy. Prolonged repeated exposure of the airways to inadequately conditioned air may induce inflammation and remodeling in competitive skiers.

Histopathologic features of early and progressive asthma.

During the last decade, morphologic studies on bronchial biopsy specimens have led to our present understanding of asthma as an inflammatory airways disease. However, little knowledge exists about the sequence of cellular events during the disease or of possible mucosal changes early in asthma. So far the primary cause, the site of damage, and the mechanisms inducing the inflammatory reaction remain to be elucidated. A multifactorial genetic susceptibility may be important for the development of asthma. Suggested factors that may trigger changes in the cells' morphologic and functional phenotype are viral infections, allergen exposure, maternal factors, diet, and smoking. Current evidence has implied that interactions between epithelial cells and the subepithelial connective tissue in the mucosa are important for normal homeostatic balance. Changes in airway epithelial phenotype possibly resulting from altered gene expression in its lining cells may be very important even as a first line change in asthma.

Early interventions in asthma with inhaled corticosteroids.

We have earlier shown epithelial damage in the airway mucosa in patients with asthma. Later other structural changes have been recognized in asthma, such as deposition of collagen and tenascin in the subepithelial basement membrane and changes in the laminin subchain composition. These processes are modified by an inflammatory process in the airways. Both the United States National Institutes of Health and the British Thoracic Society guidelines on the management of asthma emphasize the need for early use of anti-inflammatory drugs. Many clinical studies that used airway biopsy specimens have shown a decrease in airway inflammatory cell numbers after inhaled corticosteroid therapy. However, there is very little information on the effects of asthma medication on the structural components of the airways. Both the synthesis and degradation of many extracellular matrix components may be affected by the disease process and the drugs resulting in altered remodeling and gene expression in the airways. Because there are only a few studies that try to identify early changes in asthma, it is not known whether the anti-inflammatory treatment of asthma proposed by the guidelines is started early enough.

Regular albuterol or nedocromil sodium--effects on airway subepithelial tenascin in asthma.

Both albuterol and nedocromil sodium have been recognized to possess certain anti-inflammatory properties. However, there are no data on the impact of these drugs on the pathophysiology of the bronchial extracellular matrix in asthma characterized by enhanced tenascin (Tn) expression, known to occur proportional to the severity of asthma. This paper reports data from a morphometric study on the effects of regular treatment with inhaled albuterol or nedocromil sodium on the extent of bronchial subepithelial deposition of Tn, collagen types III, IV, and VII and mucosal infiltration with macrophages. Thirty-two patients (14 women) with chronic asthma, aged 38.7 years (median) with a median forced expiratory volume in 1 sec (FEV1) of 74.4% predicted, were selected to undergo fibre-optic bronchoscopy with bronchial biopsies before and after 12 weeks of treatment with either inhaled albuterol 0.2 mg or nedocromil sodium 4 mg four times daily according to a double-blind protocol. Cryostat sections of the biopsy specimens were studied by indirect immunostaining techniques using monoclonal antibodies and computer-assisted quantitative image analysis. Albuterol treatment significantly reduced the median thickness of subepithelial Tn expression from 9.7 to 6.3 microns (P = 0.023) and macrophage numbers in the epithelium (P = 0.034), lamina propria (P = 0.039) and entire mucosa (P = 0.033), whereas nedocromil sodium had no effect. Expression of the collagen types was not affected by either treatment. There was no identifiable statistical difference between the two treatments for any of the outcome variables measured. Nevertheless, the results demonstrate that even a short-acting beta 2-agonist may exert anti-inflammatory potential sufficient to interfere with the basic mechanisms of asthma as shown by reduction of subepithelial Tn content and mucosal macrophage count.

Lymphoid aggregates in endobronchial biopsies from young elite cross-country skiers.

Observation of bronchus-associated lymphoid tissue (BALT) in whole lung specimens from healthy nonsmoking adults has questioned the hypothesis that BALT is not constitutively present in healthy adult human lungs. In our study, we investigated endobronchial biopsies of the second- and third-generation carinae from 44 cross-country ski athletes and 12 healthy control subjects, all nonsmoking young adults. The skiers had a prevalence of respiratory allergy (18%), asthma-like symptoms (59%), beta2 agonist medication (25%), and methacholine bronchial hyperresponsiveness (79%). Biopsy sections were stained by immunohistochemical and hematoxylin-eosin-saffran methods. Lymphoid aggregates of more than 50 cells were identified in 28 (64%) skiers and three (25%) control subjects (p = 0.02). They were small in comparison to those found in rabbits and rats, contained T and B lymphocytes and macrophages, and were seen more frequently in skiers using beta2 agonists (p = 0.04) and with bronchial hyperresponsiveness to methacholine (p = 0.053). The frequency of these aggregates was not significantly different at the two carinal levels (p = 0.6). The aggregates were not associated with a history of respiratory allergy or asthma-like symptoms. These aggregates share some resemblance with what is usually defined as BALT. However, their exact nature and function await further clarification.

Tenascin is increased in airway basement membrane of asthmatics and decreased by an inhaled steroid.

Tenascin and fibronectin are extracellular matrix glycoproteins expressed during morphogenesis and tissue repair. In the present study bronchial biopsies were studied by the morphometric method of immunocytochemistry to reveal the distribution of different tenascin and fibronectin isoforms as well as the presence of inflammatory cells in the airway mucosa of patients with chronic asthma (n = 32) and those with seasonal birch-pollen-sensitive asthma out of season (n = 17), both in comparison with healthy control subjects (n = 12). The results showed an increase in tenascin immunoreactivity in the bronchial subepithelial reticular basement membrane layer in patients with chronic asthma (p < 0.0001) and in those with seasonal asthma (p < 0.01) compared with control subjects. The tenascin immunoreactivity, appearing as an intense wide subepithelial band in asthma, was seen only occasionally in the basement membrane of control specimens. Instead, a diffuse immunoreaction against both total fibronectin and locally produced extradomain A fibronectin was similarly visible in the airway mucosa of both patients and control subjects. Despite the significant increase in the airway mucosa of eosinophils and lymphocytes in patients with chronic asthma (p < 0.0001 and p < 0.0001, respectively) and of eosinophils in patients with seasonal asthma (p < 0.001), there was no correlation between the number of these cell types and level of tenascin expression. In patients with birch-pollen-sensitive asthma during the birch-pollen season, inhaled corticosteroid treatment, budesonide 400 micrograms twice daily, decreased tenascin immunoreactivity, in comparison with effects of placebo (p = 0.01). Our results suggest that the higher amount of tenascin reflects disease activity in asthma and may be an indicator of a remodeling process rather than of injury itself.

Two novel mutations in a Canadian family with aspartylglucosaminuria and early outcome post bone marrow transplantation.

Aspartylglucosaminuria (AGU) is a lysosomal storage disease caused by deficiency of aspartylglucosaminidase. The disease is overrepresented in the Finnish population, in which one missense mutation (Cys163Ser) is responsible for 98% of the disease alleles. The few non-Finnish cases of AGU which have been analyzed at molecular level have revealed a spectrum of different mutations. Here, we report two new missense mutations causing AGU in two Canadian siblings. The patients were compound heterozygotes with a G299-->A transition causing a Gly100-->Gln substitution and a T404-->C transition resulting in a Phe135-->Ser change in the cDNA coding for aspartylglucosaminidase. The younger patient recently underwent bone marrow transplantation.

Bronchial biopsy findings in intermittent or "early" asthma.

Bronchial biopsy specimens from subjects with intermittent or "early" asthma were compared with specimens taken from healthy subjects. Patients with early asthma included those with seasonal asthma and occupational asthma. There was a small but statistically significant increase in the thickness of the subepithelial extracellular matrix protein tenascin in subjects with seasonal and occupational asthma compared with control subjects. Collagen types IV and VII were increased only in patients with occupational asthma. Eosinophils were the only inflammatory cells that were significantly increased in subjects with seasonal asthma compared with control subjects. These data show that inflammation is present in the airways of patients with early asthma, and the increase in tenascin expression in the basement membrane zone suggests that structural changes are also initiated at an early stage of the disease.

Effect of regular nedocromil sodium or albuterol on bronchial inflammation in chronic asthma.

Nedocromil sodium is recommended for daily treatment of mild persistent asthma but its effect on cellular changes in asthmatic airways is poorly understood. We compared the antiinflammatory effects of nedocromil sodium and albuterol in 32 patients with asthma who received either nedocromil sodium 4 mg or albuterol 0.2 mg four times daily for 12 weeks according to a double-blind protocol. Patients underwent fiberoptic bronchoscopy, and lung function and bronchial responsiveness to histamine were measured. Numbers of inflammatory cells were studied by immunohistochemistry and image analysis. We were unable to identify any statistical differences between treatment groups for any of the variables measured. We conclude that our immunohistochemical study does not support the concept of nedocromil sodium as a potent/antiinflammatory drug.

Expression of laminins in the airways in various types of asthmatic patients: a morphometric study.

Laminins (Ln) are crucial in airway morphogenesis. Because they are able to interact with inflammatory cells, they are likely to participate in inflammation accompanied by airway structural remodeling in asthma. Taking biopsies and using immunohistochemistry and quantitative image analysis, we characterized the distribution of Ln chains alpha 1, alpha 2, and beta 2 in the bronchial mucosa of patients with seasonal (n = 17), early occupational (n = 8), and chronic asthma (n = 16) for comparison with that of normal controls (n = 8). In all asthmatic patients, both Ln chains alpha 1 and beta 2 were confined to the superficial margin of the basement membrane (BM), blood vessels, and smooth muscle. The thickness of Ln beta 2 expression in BM was significantly greater in patients with chronic (1.9 +/- 0.1 microns; P < 0.001) and occupational asthma (1.7 +/- 0.1 microns; P < 0.05) than in controls (0.4 +/- 0.3 microns). Only in patients with occupational asthma was the thickness of the Ln alpha 1 layer (2.3 +/- 0.2 microns; mean +/- SEM) significantly different from that in controls (1.4 +/- 0.5 microns; P < 0.05). There was no immunoreactivity for the Ln alpha 2 chain in controls or patients with mild asthma, but in clinically severe chronic asthma we found a discontinuous staining along the epithelial margin of the BM. Since Ln chains alpha 2 and beta 2 appear to function only during morphogenesis, increased expression of these Ln chains in adult asthma patients suggests accelerated tissue turnover in the airways, possibly as a result of airway inflammation in asthma.