Biomedical subjects

N Hara

Publications and source records attributed to N Hara.

At least 91 records · Page 5Linked to original sources

PubMed2000

[Lung cancer risk and genetic polymorphism at the glutathione S-transferase P1 locus in male Japanese].

The glutathione S-transferases (GSTs) are widely expressed in mammalian tissues and involved in Phase II detoxification reactions. The GSTs form a supergene family consisting of four distinct families, named alpha (GSTA), mu (GSTM) theta (GSTT) and pi (GSTP). Several of the GST genes are polymorphic in humans and are currently being investigated as possible cancer-risk modifiers. Among the GST genes, we examined GSTP1 polymorphism in exon 5 among male lung cancer patients (n = 86, male Japanese) and male healthy controls (n = 80, male Japanese) by restriction fragment length polymorphism-polymerase chain reaction method. The cancer patients showed frequency of the GSTP1 mutated genotype (individuals having at least one mutant allele, 29.1%) very similar to that of the control subjects (28.8%). After adjusting for smoking status, no association was found between the GSTP1 mutated genotype and lung cancer risk (odds ratio: 0.95; 95% confidence interval: 0.48-1.90). When study subjects were divided into two subgroups based on smoking status, the GSTP1 mutated genotype was not associated with an increased risk of lung cancer among smokers and non-smokers. These results suggest that GSTP1 polymorphism in exon 5 alone may not increase the risk of lung cancer in male Japanese.

Adult↗

PubMed2000

[A case of latex allergy with bronchial asthma].

A 26-year-old nurse consulted our department because of shortness of breath, wheezing and skin eruption after eating lunch several days before. At the consultation, the symptoms had disappeared, pulmonary function showed no abnormality, and there were no abnormal findings on chest auscultation. Latex allergy was suspected because of a history of wheezing and skin eruption after wearing latex gloves and an elevated serum IgE level specific to latex antigen. After a usage test of medical latex gloves, wheezing, skin eruption, and a decrease of FEV1.0 on pulmonary function testing were observed. The case was therefore diagnosed as latex allergy with bronchial asthma. Her symptoms were not observed after polymer coated gloves were substituted. Latex allergy is apt to complicate food allergy, an initial symptom of the present case. Specific IgE for several kinds of food was also elevated.

Adult↗

PubMed1999

Benzo[a]pyrene activates the human p53 gene through induction of nuclear factor kappaB activity.

p53 is known to be recruited in response to DNA-damaging genotoxic stress and plays an important role in maintaining the integrity of the genome. In the present study, the effect of a potent lung cancer carcinogen, benzo[a]pyrene (B[a]P) on p53 expression was investigated. We showed that exposure of A549 and NIH 3T3 cells to B[a]P resulted in an increase in p53 mRNA levels and in p53 promoter activation, indicating that B[a]P-induced p53 expression is partly regulated at the transcriptional level. The p53 promoter region which extends from -58 to -43, overlapping the kappaB motif, is essential for both the p53 basal promoter activity and p53 promoter activation induced by B[a]P. Nuclear factor kappaB (NF-kappaB) proteins have been revealed to be activated in B[a]P-induced p53 expression. Activated NF-kappaB complexes were shown to contain predominantly p50 and p65 subunit components in A549 cells and p65 subunit in NIH 3T3 cells. In addition, the overexpression of IkappaBalpha completely inhibited NF-kappaB activation, p53 promoter transactivation and the stimulatory effect on p53 transcription induced by B[a]P. We therefore conclude that B[a]P transcriptionally activates the human p53 gene through the induction of NF-kappaB activity.

3T3 Cells↗

PubMed1999

Effect of inhaled glucocorticoid on the cellular profile and cytokine levels in induced sputum from asthmatic patients.

Cytokines are considered to play a role in the airway inflammation of bronchial asthma. We examined the cellular profile and cytokine levels in induced sputum samples obtained before and after treatment with beclomethasone dipropionate (BDP, 800 microg/day, for 4 weeks) in 12 mild to moderate asthmatic subjects who had not previously received inhaled glucocorticosteroids. Sputum was induced with a 20-min inhalation of 3% saline by an ultrasonic nebulizer. The freshly expectorated sputum separated from the saliva was analyzed for cell counts, for the concentration of interleukin-8 (IL-8), and for the concentration of granulocyte-macrophage colony-stimulating factor (GM-CSF). The mean percentage of eosinophils in the sputum samples decreased significantly after BDP treatment, but no significant change in the percentage of neutrophils was observed. The mean IL-8 and GM-CSF levels also decreased significantly after treatment. The BDP treatment was associated with an increase in the mean peak expiratory flow (PEF) and with a decrease in the diurnal variation of PEF. These results suggest that inhaled steroids improve airway inflammation and lung function in asthmatics, presumably in part by inhibiting the synthesis of inflammatory cytokines such as IL-8 and GM-CSF.

Administration, Inhalation↗

PubMed1999

Role of nitric oxide released from iNANC neurons in airway responsiveness in cats.

The precise role of inhibitory nonadrenergic noncholinergic (iNANC) neurons and nitric oxide in airway hyperresponsiveness remains uncertain. The role of NO in the regulation of airway responsiveness was studied in anaesthetized and mechanically ventilated cats. To assess airway responsiveness, the changes in total pulmonary resistance (RL) produced by delivering serotonin aerosol to the airways were measured before and after N(omega)-nitro-L-arginine methyl ester (L-NAME), or a ganglionic blocker, hexamethonium, which has been reported to block iNANC. Serotonin was chosen because it causes bronchoconstriction in part by neural reflex. To further clarify the mechanism(s) involved, the effect of inhaled capsaicin was also determined in animals with sustained bronchoconstriction induced by serotonin after treatment with atropine and propranolol. Inhibition of NO synthase by L-NAME or blockade of iNANC neurons by hexamethonium significantly increased airway responsiveness. However, addition of L-NAME did not further increase airway responsiveness in animals treated with hexamethonium. In the presence of atropine and propranolol, inhaled capsaicin caused a marked bronchodilation during serotonin-induced sustained bronchoconstriction. The bronchodilation induced by capsaicin was significantly suppressed by hexamethonium and by L-NAME. These results suggest that the nitric oxide released from inhibitory nonadrenergic noncholinergic neurons is important in modulating the airway responsiveness of cats in vivo.

Airway Resistance↗

PubMed1999

Granulocyte, granulocyte-macrophage, and macrophage colony-stimulating factors can stimulate the invasive capacity of human lung cancer cells.

We and other researchers have previously found that colony-stimulating factors (CSFs), which generally include granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF), promote invasion by lung cancer cells. In the present study, we studied the effects of these CSFs on gelatinase production, urokinase plasminogen activator (uPA) production and their activity in human lung cancer cells. Gelatin zymographs of conditioned media derived from human lung adenocarcinoma cell lines revealed two major bands of gelatinase activity at 68 and 92 kDa, which were characterized as matrix metalloproteinase (MMP)-2 and MMP-9 respectively. Treatment with CSFs increased the 68- and 92-kDa activity and converted some of a 92-kDa proenzyme to an 82-kDa enzyme that was consistent with an active form of the MMP-9. Plasminogen activator zymographs of the conditioned media from the cancer cells showed that CSF treatment resulted in an increase in a 48-55 kDa plasminogen-dependent gelatinolytic activity that was characterized as human uPA. The conditioned medium from the cancer cells treated with CSFs stimulated the conversion of plasminogen to plasmin, providing a direct demonstration of the ability of enhanced uPA to increase plasmin-dependent proteolysis. The enhanced invasive behaviour of the cancer cells stimulated by CSFs was well correlated with the increase in MMPs and uPA activities. These data suggest that the enhanced production of extracellular matrix-degrading proteinases by the cancer cells in response to CSF treatment may represent a biochemical mechanism which promotes the invasive behaviour of the cancer cells.

Adenocarcinoma↗

PubMed1999

Mouse Rt6.1 is a thiol-dependent arginine-specific ADP-ribosyltransferase.

Mouse T-cell antigens Rt6.1 and Rt6.2 are glycosylphosphatidylinositol-anchored arginine-specific adenosine diphosphate (ADP)-ribosyltransferases. In the present study, we obtained evidence that an arginine-specific ADP-ribosyltransferase activity liberated from BALB/c mouse splenocytes by phosphatidylinositol-specific phospholipase C increased fivefold in the presence of dithiothreitol and that the activity was immunoprecipitated by polyclonal antibodies generated against recombinant rat RT6.1. When mouse Rt6.1 was expressed as a recombinant protein, the transferase activity of Rt6.1 was stimulated by dithiothreitol, and inhibited by N-ethylmaleimide, while activities of recombinant mouse Rt6.2 and the Glu-207 mutant of rat RT6.1 [Hara, N., Tsuchiya, M., and Shimoyama, M. (1996) J. Biol. Chem. 271, 29552-29555] were unaffected by either agent. In addition to four cysteine residues conserved among mouse Rt6 and rat RT6 antigens, Rt6.1 has two extra cysteine residues at positions 80 and 201. To investigate a contribution of these extra cysteines in mouse Rt6.1 to thiol dependency of Rt6.1 transferase activity, Cys-80 and Cys-201 of Rt6.1 were replaced with serine and phenylalanine, respectively, the corresponding residues of mouse Rt6. 2 and rat RT6.1. Transferase activity of the Phe-201 mutant of Rt6.1 lost thiol dependency while that of the Ser-80 mutant remained thiol-dependent. Thus, we conclude that mouse Rt6.1 is a thiol-dependent arginine-specific ADP-ribosyltransferase, and that Cys-201 confers thiol dependency on Rt6.1 transferase. Our study indicates that arginine-specific ADP-ribosyltransferase activity detected on BALB/c mouse splenocytes is attributed to Rt6.1 and that Rt6.1 differs from Rt6.2 in enzymatic property of the transferase and perhaps in immunoregulatory functions.

ADP Ribose Transferases↗

PubMed1999

Effect of the Chinese herbal medicine, Bakumondo-to, on airway hyperresponsiveness induced by ozone exposure in guinea-pigs.

OBJECTIVE: Bakumondo-to (Maimendong tang) is a Chinese herbal medicine that has been used as an anti-tussive agent. However, the effects of Bakumondo-to on airway hyperresponsiveness are unknown. We examine whether Bakumondo-to can inhibit airway hyperresponsiveness induced by ozone. METHODOLOGY: Measurements of airway responsiveness and plasma extravasation and bronchoalveolar lavage (BAL) were performed before and after ozone exposure (3 p.p.m., 2 h). Guinea-pigs were anaesthetized with pentobarbital sodium and mechanically ventilated. Airway responsiveness was determined by an inhalation of doubling concentration of histamine, and the concentration of histamine required to produce a 200% increase in R(L) (PC200) was calculated by log-linear interpolation. Plasma extravasation was evaluated by measuring the extravasation of Evans blue dye in the airway. RESULTS: Ozone produced significant airway hyperresponsiveness and plasma extravasation, with an influx of neutrophils in BAL fluid. Bakumondo-to (400 mg/kg p.o.) significantly inhibited airway hyperresponsiveness, but had no effect on neutrophil influx or plasma extravasation. CONCLUSIONS: We demonstrated that Bakumondo-to can attenuate airway hyperresponsiveness induced by ozone without affecting airway inflammation, which suggests that Bakumondo-to may act on the subsequent mechanisms after the induction of inflammation, such as mediator release.

Airway Resistance↗

PubMed1999

Second-line chemotherapy with weekly cisplatin and irinotecan in patients with refractory lung cancer.

Cisplatin and irinotecan are reported to act synergistically. The authors have conducted a phase II trial combining cisplatin and irinotecan in patients with refractory lung cancer to evaluate the activity and safety of the regimen. Twenty-one patients, who had not responded to prior platinum-based chemotherapy, were entered into the study. Both cisplatin (30 mg/m2) and irinotecan (60 mg/m2) were administrated on days 1, 8, and 15, and the regimen was repeated every 28 days. There were six partial responses, and the response rate was 29% (95% confidence interval, 11.3%-52.2%). The median survival time of all patients was 32 weeks, and 1-year and 2-year survival rates were 43% and 11%, respectively. Major toxicities were hematologic; leukopenia of grades 3 and 4 developed in 43% patients, anemia developed in 38%, and thrombocytopenia developed in 19%. One notable nonhematologic toxicity was diarrhea; which was grade 3 in 38%. The weekly chemotherapy combining cisplatin and irinotecan was active against lung cancer, which is refractory to platinum-based chemotherapy. However, skips of drug administration or dose reduction were necessary in 76% patients during two courses of planned administration, though the ratio of actual dose to scheduled dose was 81%. Dose modification would be necessary to yield better results by this weekly chemotherapy.

Adult↗

PubMed1999

Expression of p53 and glutathione S-transferase-pi relates to clinical drug resistance in non-small cell lung cancer.

To determine the predictive value of the expression of p53 and glutathione S-transferase-pi (GST-pi) with respect to chemotherapy response, immunostaining was performed on transbronchial biopsy specimens from previously untreated patients with non-small cell lung cancer. Of the 54 patients, 34 patients (63%) and 37 patients (69%) were positive for p53 and GST-pi, respectively. The response rates in the p53-positive and p53-negative group were 15 and 45%, and those in GST-pi-positive and GST-pi-negative groups were 16 and 47%, respectively. A multiple logistic regression analysis revealed that positive immunostaining for GST-pi was a significant risk factor for clinical chemotherapy resistance. The combination of these two markers was the most important independent factor in predicting a response to chemotherapy in multiple logistic regression analysis. Immunohistochemical expression of p53 and GST-pi was independently related to clinical chemoresistance in patients with non-small cell lung cancer. Combined use of these two biomarkers may be a useful predictor of clinical chemoresistance.

Adult↗

PubMed1999

Expression of B7-1, B7-2, and interleukin-12 in anti-Fas antibody-induced pulmonary fibrosis in mice.

BACKGROUND: We have previously reported that the inhalation of anti-Fas antibody induced pulmonary fibrosis in mice. To induce an effective immune response, antigen-presenting cells have to not only present antigenic peptide with MHC molecules to T lymphocytes, but also express B7 costimulating molecules. The purpose of this study is to investigate whether B7 family costimulating molecules and interleukin-12 (IL-12), which primarily promote cellular immunity, are associated with anti-Fas antibody-induced pulmonary fibrosis. METHODS: We examined the expression of B7-1, B7-2, and IL-12 using the revese transcription-polymerase chain reaction (RT-PCR), RT-in situ PCR, and immunohistochemistry. RESULTS: We observed the upregulation of B7-1, B7-2, and IL-12 p40 mRNA after anti-Fas antibody inhalation. B7-2 and IL-12 p40 mRNA appeared to be expressed in mononuclear cells, while B7-1 mRNA and protein were expressed in bronchiolar epithelial cells as well as macrophages. CONCLUSION: These findings indicate that the T-cell-mediated immune response in this model involved the upregulation of B7-1, B7-2, and IL-12, and that the aberrant expression of B7-1 in bronchiolar epithelial cells may induce autoreactive T cell proliferation against themselves.

Administration, Inhalation↗

PubMed1999

Effect of endothelin-1 on the serotonin-induced contraction of smooth muscle in the guinea pig trachea.

BACKGROUND: Endothelin (ET), a potent constrictor of smooth muscle including that of the airways, may contribute to the development of airway hyperresponsiveness. OBJECTIVE: To investigate the role of ET-1 on the airway smooth muscle, we examined the effects of ET-1 on the serotonin-induced contraction of guinea pig tracheal smooth muscle. METHODS: The changes in isometric tension evoked by serotonin were measured before and after the application of a subthreshold dose (a dose which did not induce smooth muscle contraction by itself) of ET-1. RESULTS: Serotonin caused smooth muscle contraction in a dose-dependent manner. The subthreshold doses of ET-1 (1 pM) and sarafotoxin 6c (1 pM), a selective ETB receptor agonist, were found to potentiate significantly the contraction induced by serotonin. A potentiating effect of ET-1 was not altered by indomethacin or calphostin C, a protein kinase C inhibitor. CONCLUSION: These results suggest that a subthreshold concentration of ET-1 can potentiate serotonin-induced contraction of smooth muscle through the activation of ETB receptor, while in contrast cyclooxygenase and protein kinase C were found not to be involved in this mechanism.

Animals↗

PubMed1999

Immunohistochemical localization of B7 costimulating molecules and major histocompatibility complex class II antigen in pulmonary sarcoidosis.

BACKGROUND: Alveolar macrophages (AM) of sarcoidosis have an enhanced capacity to mediate antigen-induced T lymphocyte proliferation. To induce an effective immune response, antigen-presenting cells have to not only present antigenic peptide with MHC molecules to T lymphocytes, but also express B7 costimulating molecules. OBJECTIVE: The purpose of this study was to investigate the expression of B7 and MHC molecules in lung tissues from patients with sarcoidosis. METHODS: We performed immunohistochemistry for B7-1, B7-2 and MHC class II antigens using transbronchial lung biopsy specimens obtained from patients with sarcoidosis and normal lung parenchyma obtained by lobectomy for solitary pulmonary nodule as controls. RESULTS: B7-1, B7-2 and MHC class II antigen were expressed in epithelioid cells in granulomas in 14 (93.3%), 2 (13.3%) and 9 (60.0%) of 15 patients with sarcoidosis, respectively. These were also expressed in AM in 14 (93. 3%), 5 (33.3%) and 12 (80.0%) of 15 patients with sarcoidosis, respectively. The positivity of B7-1 was significantly higher than that of B7-2 in both epithelioid cells and AM in sarcoidosis (p < 0. 01). Positive signals for B7-1, B7-2 and MHC class II antigen were also found in AM in 9 (90%), 8 (80%) and 8 (80%) of 15 of controls, respectively. However, the intensity of positive signals for B7-1, but not B7-2 or MHC class II antigen in AM was significantly increased in sarcoidosis compared to controls (p < 0.05). CONCLUSIONS: These results suggested that epithelioid cells in granulomas and AM from patients with sarcoidosis had the capability to act as accessory cells and that the accessory function of these cells was shifted to B7-1 rather than B7-2 in sarcoidosis.

B7-1 Antigen↗

PubMed1999

The involvement of Fas-Fas ligand pathway in fibrosing lung diseases.

Pulmonary fibrosis begins with alveolitis, which progresses to destruction of lung tissue and excess collagen deposition. This process could be the result of DNA damage and a form of apoptosis. Therefore, we hypothesized that Fas ligand (FasL), which induces apoptosis in cells expressing Fas antigen (Fas), is associated with pulmonary fibrosis. We examined frozen lung tissues from seven patients with idiopathic pulmonary fibrosis (IPF), and bronchoalveolar lavage fluid (BALF) cells from 19 patients with IPF and from 17 patients with interstitial pneumonia associated with collagen vascular diseases (CVD-IP). We used five frozen lungs with normal lung parenchyma and BALF cells from 10 patients with solitary pulmonary nodule as controls. Reverse transcription-polymerase chain reaction (RT-PCR) showed that FasL messenger RNA (mRNA) was expressed in BALF cells from all patients with IPF and from 15 of 16 patients with CVD-IP. FasL mRNA was not detected in BALF cells except in one of 10 controls. RT in situ PCR detected FasL mRNA in inflammatory cells in BALF from patients with IPF. Immunohistochemistry detected FasL protein in infiltrating lymphocytes and granulocytes in all of seven frozen lung tissues of IPF, but in none of five control lung tissues. Additionally, the expression of Fas appeared to be upregulated in bronchiolar and alveolar epithelial cells in IPF compared with normal lung parenchyma by immunohistochemistry. We conclude that Fas and FasL were upregulated in fibrosing lung diseases and may associate with DNA damage or apoptosis of bronchiolar and alveolar epithelial cells in this disorder.

Adult↗

PubMed1999

Frequent expression of p53 protein without mutation in the atypical epithelium of human bronchus.

We investigated the correlation between p53 protein levels and mutations in the p53 gene of atypical bronchial epithelium (ABE). Protein levels were analyzed by immunohistochemistry, whereas mutations were assessed by polymerase chain reaction-single-strand conformational polymorphism (PCR-SSCP) and direct sequencing. A total of 78 formalin-fixed, paraffin-embedded bronchial biopsy specimens that had been diagnosed to be ABE were retrieved from the archives and examined. p53 protein was expressed in 44 of the 78 (56%) specimens overall. However, when pathologically classified, 38% of hyperplasias, 58% of metaplasias, and 73% of dysplasias were positive, indicating that an increased frequency of p53 expression correlated with the severity of ABE (P = 0.042). Among the 44 specimens that expressed p53 protein, 40 (91%) did not reveal mutations by PCR-SSCP. In the four specimens with abnormal PCR-SSCP bands, p53 gene mutation was identified by direct sequencing and revealed the same point mutation at codon 248 (CGG-to-CTG transversion) of exon 7 in all four specimens. These four specimens were dysplasias derived from patients with lung cancer. p53 protein expression in ABE was associated with the wild-type gene in most cases; therefore, wild-type p53 protein expressed in ABE might have a protective function from lung carcinogenesis, and mutation of p53 gene may be a late event in the sequential steps of lung carcinogenesis.

Adolescent↗

PubMed1999

Induction of interleukin-8 secretion and apoptosis in bronchiolar epithelial cells by Fas ligation.

Epithelial cell injury is the common manifestation of lung injury. Contributing to such injury of epithelial cells is apoptosis. Although apoptosis is part of the normal process of epithelial renewal, in excess it is pathologic. We previously demonstrated the excessive apoptosis of lung epithelial cells and the upregulation of Fas and Fas ligand (FasL) in fibrosing lung diseases. We also showed that inhalation of anti-Fas antibody induced lung injury and fibrosis in mice. Interleukin (IL)-8 is one of the most important cytokines in the pathophysiology of acute lung injury and pulmonary fibrosis. In this study we investigated whether Fas ligation induces IL-8 secretion in addition to apoptosis in bronchiolar epithelial cells in vitro. Bronchiolar epithelial cells underwent apoptosis and also secreted IL-8 in response to tumor necrosis factor (TNF)-alpha or Fas ligation. New gene expression and protein synthesis were not necessary for Fas ligation- and TNF-alpha- mediated apoptosis, but were necessary for IL-8 secretion. We further found that Fas ligation induced activation of nuclear factor-kappa B. We conclude that the Fas/FasL pathway not only mediates apoptosis but also plays a proinflammatory role, and that stimulation of the Fas/FasL pathway in bronchiolar epithelial cells leads to IL-8 production, which may amplify the inflammatory cascade in lung injury and pulmonary fibrosis.

Antibodies, Monoclonal↗

PubMed1999

Essential roles of the Fas-Fas ligand pathway in the development of pulmonary fibrosis.

The Fas ligand is predominantly expressed in activated T lymphocytes and is one of the major effector molecules of cytotoxic T lymphocytes and natural killer cells. Previously, we found excessive apoptosis of epithelial cells and infiltrating lymphocytes expressing Fas ligand mRNA in the lung tissue of bleomycin-induced pulmonary fibrosis in mice. Here we demonstrated that the administration of a soluble form of Fas antigen or anti-Fas ligand antibody prevented the development of this model and that lpr and gld mice were resistant against the induction of pneumopathy. These results suggest that the Fas-Fas ligand pathway plays an essential role in the development of pulmonary fibrosis and that preventing this pathway could have therapeutic value in lung injury and fibrosis.

Animals↗

PubMed1999

Apoptosis in the course of granulomatous inflammation in pulmonary sarcoidosis.

Sarcoidosis is a chronic inflammatory disease of unknown aetiology characterized by the formation of non-necrotizing granulomas. The course of disease is usually self-limiting with the spontaneous resolution of granuloma. In the immune system, Fas antigen (Fas) and Fas ligand (FasL) are involved in the down regulation of immune reactions by inducing apoptosis. Therefore, it was hypothesized that the Fas/FasL pathway and apoptosis may be associated with the course of granulomatous inflammation in sarcoidosis. Terminal deoxynucleotidyl transferase-mediated biotin nick end-labelling (TUNEL) was performed to assess deoxyribonucleic acid strand breakages as a characteristic of apoptosis. Immunohistochemistry was also performed to detect Fas and FasL protein, and reverse transcriptase polymerase chain reaction (RT-PCR) and RT in situ PCR to detect FasL messenger ribonucleic acid (mRNA). Positive signals for TUNEL were detected in epithelioid histiocytes and lymphocytes within granulomas and in bronchoalveolar lavage (BAL) lymphocytes from patients with sarcoidosis. Positive signals for Fas were also detected in these cells. FasL mRNA was expressed in BAL lymphocytes from 15 of 20 patients with sarcoidosis, but from only one of 10 patients with normal lung parenchyma. FasL protein was expressed in lymphocytes surrounding and within the granuloma. There was a significant correlation between the result of TUNEL and clinical course in patients with sarcoidosis. Apoptosis in epithelioid histiocytes and inflammatory cells seems to participate in the course of granulomatous inflammation. Further studies are needed to determine the role of Fas, FasL and other regulatory factors in apoptosis in the granulomatous inflammation in pulmonary sarcoidosis.

Adult↗