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High concentration of (1-->3)-beta-D-glucan in BAL fluid in patients with acute eosinophilic pneumonia.

Our aim in the study was to investigate the pathogenesis of eosinophilic inflammation in patients with acute eosinophilic pneumonia (AEP), and to determine the levels of (1-->3)-beta-D-glucan, which is one of the major components of the cell wall of most fungi, in the BAL fluid (BALF) of those patients with AEP. Six patients with AEP and five patients with chronic eosinophilic pneumonia (CEP) that was in the acute stage and had been newly diagnosed, and nine healthy subjects from the Kurume University School of Medicine and the Social Institute Tagawa Hospital between 1995 and 2001 were entered into the study. In AEP patients, (1-->3)-beta-D-glucan was detected in BALF, and these findings were compared with BALF findings in patients with CEP as well as with those in healthy subjects. In the BALF of AEP patients, the mean concentration of (1-->3)-beta-D-glucan was significantly higher (p < 0.05) than that of CEP patients as well as healthy subjects. In patients with AEP, the mean concentration of (1-->3)-beta-D-glucan in BALF was significantly higher (p < 0.05) than that in the blood. In four of six patients with AEP, we measured serial changes in (1-->3)-beta-D-glucan levels, and the level of (1-->3)-beta-D-glucan in the BALF decreased with clinical improvement at follow-up. We concluded that inhaled (1-->3)-beta-D-glucan may be involved in the mechanisms of pulmonary inflammation in patients with AEP.

Acute Disease↗

Electron microscopic findings in BAL of a fire-eater after petroleum aspiration.

Hydrocarbon pneumonitis, known also as fire-eater pneumonia, always develops after aspiration of low-viscosity, volatile hydrocarbides. Despite the presence of clear-cut indicators for an infection, it is considered to be an acute pseudoinfectious lung disease. In this article, we report on a relatively rare clinical picture of a 30-year-old man after accidental petroleum aspiration. In addition to the usual clinical and instrumental examinations, we also performed, for the first time, electron microscopic investigations of the BAL specimen. A striking finding was the occurrence of macrophages (40%) with numerous lipoid inclusions that exhibited all morphologic signs of an activation as well as neutrophil granulocytes (33%), lymphocytes (21%), and eosinophils (6%). Despite a large and necrotizing infiltration of the right lower lobe, the clinical course was uneventful with complete recovery.

Adult↗

Regional differences in emphysema scores and BAL glutathione levels in HIV-infected individuals.

STUDY OBJECTIVES: Evidence exists that HIV-seropositive individuals may be at increased risk for the development of precocious pulmonary emphysema. HIV infection is also associated with antioxidant deficiency in both the serum and lungs, and it is therefore possible that increased oxidant stress may contribute to parenchymal lung injury occurring in the setting of HIV. We sought to determine the regional distribution of emphysema and regional distribution of glutathione (GSH) concentrations among HIV-seropositive subjects with emphysema. DESIGN: Cross-sectional evaluation of a prospective, longitudinal study. SETTING: University teaching hospital. SUBJECTS/MEASUREMENTS: HIV-seropositive subjects without AIDS-related pulmonary complications participating in a descriptive study of lung biology in HIV-seropositive individuals. Emphysema scoring and evaluation of emphysema lobar distribution was performed among 40 subjects with emphysema. Eleven subjects underwent BAL of the right middle lobe (RML) and right upper lobe (RUL) with measurement of epithelial lining fluid (ELF) GSH in each lobe. RESULTS: We found that the mean emphysema scores were much higher in the upper lobes compared to the rest of the lung. Mean GSH levels were significantly greater in the RUL compared to the RML. The regional differences were present in both smokers and nonsmokers. CONCLUSIONS: We conclude that in the setting of HIV, emphysema is more prominent and lung GSH concentrations are higher in the upper lobes. We hypothesize that the increased GSH may represent a compensatory response to increased oxidant stress in the upper lobes.

Adult↗

Perforin down-regulation and adhesion molecules activation in pulmonary sarcoidosis: an induced sputum and BAL study.

BACKGROUND: Sarcoidosis is thought to be a T-helper type 1 cytokine-mediated disorder. Sputum induction has been proposed as a useful noninvasive method mainly for the assessment of airway diseases. However, it is unknown whether the balance of T-cytotoxic (Tc1) type 1 and Tc2 cells is altered in sarcoidosis. STUDY OBJECTIVES: The primary aim of this study was to characterize the CD8+ T lymphocyte subpopulations in induced sputum from sarcoidosis patients, and to compare these subpopulations to those found in BAL fluid (BALF) from sarcoidosis patients. To further investigate the mechanism of the cytotoxic activity of CD8+ lymphocytes, we measured their perforin expression. Additionally, two adhesion molecules (CD62 and CD71), which are expressed on CD8+ T cells and may serve as novel immunologic markers, were detected. SETTINGS: Department of Thoracic Medicine, University of Crete, and Department of Pneumonology, Democritus University of Thrace, Alexandroupolis, Greece. PATIENTS: We prospectively studied 22 patients with sarcoidosis (median age, 48 years; age range, 25 to 65 years) and 10 healthy subjects (5 female and 5 male; median age, 39 years; age range, 26 to 60 years). INTERVENTIONS: The stimulation of lymphocytes with phorbol 12-myristate 13-acetate was followed by the use of double immunocytochemical methods to identify CD8+ interferon (IFN)-gamma producing cells (ie, Tc1) and CD8+ interleukin-4 producing cells (ie, Tc2). MEASUREMENTS AND RESULTS: We found a significant decrease in the prestimulation percentage of IFN-gamma-positive CD8+ T cells in the BALF (p = 0.001) and induced sputum (p = 0.001) of sarcoidosis patients compared to the number in samples from healthy control subjects. However, no significant difference was documented between lymphocyte subsets poststimulation. Decreased levels of perforin expression were found in BALF (p = 0.001) and induced sputum (p < 0.001) of sarcoidosis patients compared to those in control subjects. The adhesion molecules were significantly increased in both the BALF and induced sputum of the sarcoid population compared to those in healthy control subjects. CONCLUSIONS: Our results suggest that inflammation could be effectively and noninvasively determined by using sputum induction in sarcoidosis patients. In addition, we have provided evidence suggesting the possibility that CD8+ lymphocytes might not play a major role in sarcoidosis.

Adult↗

Chemical composition of the essential oil of Phlomis linearis Boiss. & Bal., and biological effects on the CAM-assay: a safety evaluation.

Phlomis linearis Boiss. & Bal. of the Lamiaceae family growing in central, east and southeast Anatolia is an endemic species for Turkey. The essential oil obtained from the aerial parts by hydro distillation was subsequently analyzed by GC/MS. The main components of the oil were found as beta-caryophyllene (24.2%), germacrene D (22.3%) and caryophyllene oxide (9.2%), among 49 identified compounds, representing 94.5% of the total essential oil. The overall biological activity of the essential oil (100 microg/pellet) was tested on the chorioallantoic membrane (CAM) of the fertilized hen's egg in order to examine the anti-angiogenic and anti-inflammatory activity. None of the tests showed pronounced activity, toxicity or irritation at the tested concentration.

Allantois↗

Maltose adaptive mutant of heterotrophic marine bacterium, Alteromonas espejiana Bal-31: changes in the growth and the induction of extracellular alpha-amylase.

Growth of the heterotrophic marine bacterium, Alteromonas espejiana Bal-31 was inhibited in the presence of sucrose, maltose and even glucose, but not with starch. Extracellular alpha-amylase was induced with a lag phase of 2 h in the presence of starch. In contrast, cell growth of the S2a mutant was not affected by the addition of maltose, and starch was ineffective in the induction of extracellular alpha-amylase in this mutant. Activity of extracellular alpha-amylase was induced from the S2a mutant with a 4-h lag phase in the presence of maltose, and the high level of enzyme activity was maintained for at least 24 h. Activity of alpha-amylase induced by both wild type starch and S2a mutant maltose cultures were mainly observed in extracellular locations. This activity could be stopped by tetracycline treatment, indicating that enzyme induction was dependant on gene expression and not on enzyme protein secretory mechanisms. Our results showed that the mutation in S2a changed the growth and the modulation of the specific alpha-amylase in response to carbon nutrients.

Adaptation, Physiological↗

[Chemokine RANTES in bronchoalveolar lavage fluid(BAL)from two different lung segments indicated by high resolution tomography (HRCT) in patients with sarcoidosis].

In 28 non-smoking patients with sarcoidosis (14 males, 14 females aged 19-51) the concentrations of cytokine RANTES were estimated in BAL fluid from two different lung segments: with the most (s.A) and with the least (s.B.) extensive involvement estimated by high resolution computed tomography (HRCT). In examined subjects 12 patients showed homogeneous distribution of HRCT changes (HD) in lung parenchyma and 16 showed nonhomogeneous distribution of HRCT changes (ND) with domination of pathological changes in upper lobes. Eleven healthy volunteers served as controls. In BALF from s.A and sB the significantly higher concentrations of RANTES were observed in comparison with control group (14.4 and 10.9 pg/ml vs 3.6 and 3.4 pg/ml respectively). In group (ND) in BALF from s.A (from upper lobes--the most occupied by HRCT changes) the concentrations of RANTES were significantly higher than in BALF from s.B (from lower lobes with the least involvement estimated by HRCT). RANTES concentrations in BALF from s.A and s.B positively correlated with lymphocytes count, lymphocytes CD3, CD4 and HLA-DR+ and correlated negatively with diffusing capacity in sarcoid patients. Our results suggest the significant role in pathogenesis of sarcoidosis and in alveolitis process enhancement.

Adult↗

No association between the dopamine D3 receptor Bal I polymorphism and schizophrenia in a family-based study of a Palestinian Arab population.

Several recent meta-analyses appear to show a weak but significant effect of both forms of the gly/ser DRD3 polymorphism in conferring risk for schizophrenia. Since most studies have employed the artifact-prone case-control design, we thought it worthwhile to examine the role of this polymorphism using a robust family-based strategy in an ethnic group not previously systematically studied in psychiatric genetics, Palestinian Arabs. We failed to obtain any evidence in 129 Palestinian triads, using the haplotype relative risk (allele frequency: Pearson chi-square = 0.009, P > 0.1, df = 1, n = 258 alleles) or transmission disequilibrium test design (chi-square = 0.38, P > 0.1, n = 86 families) for association/linkage (or increased homozygosity) of the DRD3 Bal I polymorphism to schizophrenia in our sample. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:778-780, 2000.

Alleles↗

[Anaerobic bacteria in bronchoalveolar lavage fluid (BAL) after thoracic surgery].

Purpose of this study was to find out what kind of anaerobic bacteria were in lower respiratory tract and how often they were present there considering patients after thoracic surgery. Also, what is susceptibility of bacteria to antibiotics. Research covered 30 patients after operation. Material for research was bronchoalveolar lavage (BAL) taken during bronchoscopy. Collected sample was cultivated in anaerobic and aerobic conditions. Anaerobic bacteria were found in 28 samples (93%). Totally there were 100 anaerobic bacteria strains. The most common Gram-negative rods were from genus Prevotella (24 strains, 24%) and Bacteroides (15 strains, 15%). Gram-negative bacteria except Bacteroides characterised biggest susceptibility to imipenem, piperacillin/tazobactam, amoxicillin/clavulanate, ampicillin/sulbactam, piperacillin, clindamycin and metronidazol. Bacteroides were susceptible to imipenem, piperacillin/tazobactam and metronidazol. Among Gram-positive anaerobic bacteria mostly were isolated from cocci Peptostreptococcus (18 strains, 18%) and were susceptible to all antibiotics. Gram-positive rods were in most cases represented by Actinomyces (12 strains 12%) and were highly susceptible to all antibacterial means except metronidazol (100% is resistant).

Aged↗

Kallikrein-like activity in the bronchoalveolar lavage (BAL) fluid of sensitized, challenged guinea-pigs.

Sensitization and challenge of guinea-pig airways with aerosols of ovalbumin solution administered through an endotracheal tube leads to a significant increase in kallikrein-like enzyme activity in bronchoalveolar lavage (BAL) fluid. This increase is present up to six hours after challenge and may be related to changes in airways resistance that persist for similar periods.

Aerosols↗

Bradykinin and other inflammatory mediators in BAL-fluid from patients with active pulmonary inflammation.

We evaluated the levels of bradykinin, albumin, TAME-esterase activity, histamine, PGD2 and LTC4 in bronchoalveolar lavage fluid from asthmatics and from patients with pneumonia, sarcoidosis, fibrosis, and chronic bronchitis. Compared with the results of healthy volunteers and atopic asymptomatic asthmatics the bradykinin levels and TAME-esterase activity were significantly elevated. In all other groups, histamine was additionally elevated in asymptomatic asthmatics, whereas albumin was elevated in symptomatic asthmatics and fibrosis patients, and decreased in chronic bronchitis and pneumonia patients. Following local intrabronchial allergen challenge of mild grass pollen asthmatics out of season bradykinin levels increased significantly, correlated with albumin, histamine and TAME-esterase activity. In contrast to the increased mediator concentrations in the early phase reaction there was no change of BAL cells in asthmatics compared to baseline and healthy volunteers. The presence of bradykinin in the bronchoalveolar space of patients with active pulmonary inflammations and bradykinin generation in asthmatics as a result of intrabronchial allergen challenge provides strong evidence that kinins are involved in inflammatory disorders of the lower airways.

Asthma↗

[A case of acute eosinophilic pneumonia with a disassociation between the KL-6 level and SP-A and SP-D levels in the serum and BAL fluid].

A 45-year-old Japanese electrical engineer was admitted to our department of internal medicine on August 12, 2003, because of a sudden high fever and severe hypoxic respiratory failure. At a barbecue with his family on August 3 beside a nearby river, he had been exposed to the smoke. From August 4 to 11, he had suffered fatigue, fever, dry cough and progressive dyspnea. On admission, his SpO2 was 84%, and computed tomography scanning showed patchy ground glass opacity, thickened bronchial walls, and bilateral pleural effusions. The eosinophil count in the bronchoalveolar lavage fluid (BALF) was increased to 52.4%. Noticeably, the KL-6, SP-A and SP-D levels in the serum were elevated to 197 U/ml, 188 ng/ml and 137 ng/ml, and their levels in BALF had also increased to 225 U/ml, 890 ng/ml and 1110 ng/ml, respectively. The lymphocyte stimulation test was negative, and the cultures of blood and BALF did not grow any pathogens. The patient had smoked 1 pack of per cigarettes day for 25 years and showed no sign of atopic illness. Acute eosinophilic pneumonia (AEP) was diagnosed, and responded dramatically to treatment with oxygen and corticosteroids. The dissociation between the normal KL-6 levels and the elevated SP-A and SP-D levels in the serum and BAL fluid may play an important role in cases of AEP.

Acute Disease↗

[Changes in the interaction of DNA with chromatin and nuclear matrix proteins during digestion of nuclei with restrictases and nuclease Bal 31].

Earlier experiments with the use of nucleoprotein-celite chromatography revealed that DNA is bound to a replicative complex localized in the nuclear matrix by a topologically tight bond. Induction of site-specific DNA breaks by restriction nucleases in isolated nuclei of proliferating cells causes a gradual concentration-dependent liberation of DNA from the tight binding to the nuclear matrix. The DNA involved in the tight interaction with matrix proteins is especially sensitive to digestion by Sau 3A1, EcoRI, PstI, BCNI and Bam HI restrictases. One-strand DNA-specific nuclease Bal 31 also destroys the tight DNA-matrix bond. The tightness of DNA-protein bonds in chromatin particles formed after the digestion of nuclei with restrictases is dependent on the particle size. The data are summarized in a model of a topological DNA-matrix bond.

Chromatin↗

Terminally directed hydrolysis of duplex ribonucleic acid catalyzed by a species of the BAL 31 nuclease from Alteromonas espejiana.

The extracellular nuclease activities of Alteromonas espejiana sp. BAL 31 are mediated by at least two distinct protein species that differ in molecular weights and catalytic properties. The two species that have been purified to homogeneity and characterized, the "fast" (F) and "slow" (S) enzymes, both possess an exonuclease activity that shortens both strands of duplex DNA, with the F nuclease displaying a much greater (approximately 19-fold) turnover number for this degradation than the S species. In the present article, it is shown that the F species also mediates the terminally directed hydrolysis of a linear duplex RNA, gradually shortening molecules of this substrate through a mechanism that results in the removal of nucleotides from both the 3' and the 5' ends. This degradation proceeds with very infrequent introduction of scissions away from the termini as demonstrated by gel electrophoretic examination of the products of partial degradation, both in duplex form and after denaturation by reaction with CH3HgOH, and by electron microscopic characterization of duplex partially degraded molecules. The apparent Michaelis constant and turnover number have been determined. At equimolar enzyme concentrations in the limit of high substrate concentration, the F nuclease will degrade duplex RNA at a rate 0.021 +/- 0.010 (S.D.) times that for a duplex DNA of comparable guanine + cytosine content. The S species, by contrast, shows very little activity against the duplex RNA substrate relative to that of the F enzyme.

Endodeoxyribonucleases↗

Isolation and comparison of two molecular species of the BAL 31 nuclease from Alteromonas espejiana with distinct kinetic properties.

The extracellular nuclease from Alteromonas espejiana sp. BAL 31 can be isolated as two distinct proteins, the "fast" (F) and "slow" (S) species, both of which have been purified to homogeneity. The F and S species of the nuclease have molecular weights, respectively, of 109 X 10(3) and 85 X 10(3), and both are single polypeptide chains with an isoelectric pH near 4.2. Both species catalyze the degradation of single-stranded and linear duplex DNAs to 5'-mononucleotides. The degradation of linear duplex DNA occurs through a terminally directed hydrolysis mechanism that results in the removal of nucleotides from both the 3' and 5' ends. Apparent Michaelis constants (Km) have been obtained for the exonuclease activities of both species and for the activity against single-stranded DNA of the S species. The Km for the hydrolysis of single-stranded DNA catalyzed by the F species has not been obtained because the reaction velocity was maximal even at the lowest substrate concentrations accessible in the photometric assay. The ratio of the turnover numbers for the exonuclease activities of the two species indicates that the F species will shorten linear duplex DNA at a rate 27 +/- 5 (S.D.) times faster than an equimolar concentration of the S species in the limit of high substrate concentration, while the corresponding ratio for the activities against single-stranded DNA (1.2 +/- 0.1) shows that the two species are similar with respect to hydrolysis of this substrate. In the limit of high substrate concentrations, the F and S species break phosphodiester bonds in single-stranded DNA at rates 1.3 +/- 0.3 and 33 +/- 2 times those for the exonucleolytic degradation of linear duplex DNA, respectively. It has not been established whether the two species are physically related.

Bacteria↗

[Acute self-poisoning with arsenic and treatment with BAL (author's transl)].

A case of attempted suicide by ingestion of 4.8 g As2O3 (more than 20 times the estimated lethal dose) is reported. Absorption of arsenic caused elevated urinary levels over 5 days BAL treatment was started within three hours after arsenic ingestion. The patient did not develop any signs of polyneuropathy or other clinical changes.

Arsenic Poisoning↗

Comparison of morphological and biochemical changes of BAL-isolated cells in experimental lung emphysema.

The aim of the study was to evaluate the protease and antiprotease activity in the fluid obtained from the culture of cells isolated from the lungs of animals with experimental emphysema. An attempt was made to correlate the results of biochemical examinations with adherence degree and ultrastructural changes of the surface of BAL-isolated cells. The experiment was carried out on male Wistar rats, of 180-220 g b.w. Two i.p. injections of BCG-vaccine (4 x 10(8) microorganisms) on the 1st and 14th day were applied as macrophage mobilizing and activating agent. Papain (2 mg/l ml/100 g b.w.) was given once i.t. on the 21st day. The animals were sacrificed on the 28th day of the experiment. We found a correlation between the increase in the cell adherence and ultrastructural changes (in SEM), suggesting an increased activity of the cells isolated from BCG-treated rats. In the culture medium of cells isolated from the rats which were given BCG or papain and BCG+papain we observed an increased base protease activity and decreased Cathepsin D activity comparing with the control group. Increased antitrypsin activity in the BCG and BCG+papain-treated rats and decreased antitrypsin activity in papain-treated rats only was observed, too. There was no obvious difference in the levels of the antiplasmin and antichymotrypsin activities between the groups. The present results indicate that activated pulmonary macrophages are one of the sources of the protease-antiprotease intraalveolar imbalance. However, an increased production of proteolytic enzymes may not be the only factor responsible for the progression of lung emphysema in BCG-treated rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Proliferating alveolar macrophages in BAL and lung function changes in interstitial lung disease.

In interstitial lung disease, the number of alveolar macrophages (AMs) can be increased. This may be caused by recruitment of precursor cells from peripheral blood and/or local proliferation in the lung. We therefore analysed proliferation, by studying both the expression of the nuclear proliferation antigen, Ki67, and the deoxyribonucleic acid (DNA) content, using the Feulgen reaction followed by cytometry. The patients had interstitial lung disease, i.e. sarcoidosis (n = 20), extrinsic allergic alveolitis (n = 20), idiopathic lung fibrosis or lung involvement in collagen-vascular disease (n = 19). In all patient groups there was a significant increase in proliferating AMs compared to healthy controls (4.2 versus 1.4% Feulgen, 2.1 versus 0.5% Ki67), with a significant correlation between these two parameters. A positive correlation was also found in bronchoalveolar lavage (BAL) between numbers of lymphocytes and proliferating cells in sarcoidosis and in fibrosis. In fibrosis, numbers of eosinophils and proliferating cells were also positively correlated. Our main finding was, however, a positive correlation between numbers of proliferating cells (Feulgen) and lung function parameters, especially vital capacity and oxygen tension (PO2) at rest, in patients with sarcoidosis and lung fibrosis. By contrast, in extrinsic allergic alveolitis, no correlation could be observed between proliferating cells and cell population or lung function. Our results suggest that local proliferation of macrophages is an important element in interstitial lung disease.

Adult↗