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[Farmer's lung cases of a farmer and his son with high BAL fluid beta-D glucan levels].

A farmer and his son, who treated straw in a cowshed, were admitted to our hospital because of severe dyspnea during summer time. Their chest X-ray films revealed bilateral reticulonodular shadows in the middle to lower lung fields. Bronchoalveolar lavage (BAL) fluid analyses showed a high proportion of lymphocytes and an increased CD4/8 ratio. They were diagnosed with farmer's lung and treated with pulse therapy with methylprednisolone and tapering of steroid. Hypoxemia and interstitial shadow improved, though the farmer relapsed one day after getting home. Immune precipitation showed positive reactions against Aspergillus fumigatus, Aspergillus terreus and Nocardiopsis alba. Their beta D-glucan levels in BAL fluid were higher than those of healthy normal volunteers, whereas their beta D-glucan levels in serum were below the detection levels. Ventilation of the cowshed and wearing a mask should prevent recurrence of the disease.

Adult↗

Toxicity induced by Hg2+ on choline acetyltransferase activity from E. electricus (L.) electrocytes: the protective effect of 2,3 dimercapto-propanol (BAL).

BACKGROUND: The effect of mercury (Hg(2+)) on the activity of choline acetyltransferase (ChAT) from electrocytes of Electrophorus electricus (L.) was studied due to the importance of this enzyme and acetylcholine in many neurochemical functions such as arousal, learning, and memory. MATERIAL/METHODS: Mercury, which has affinity to thiol groups, acted as a potent inhibitor of ChAT, which was obtained by differential centrifugation and ammonium sulfate precipitation, at 80%, from the main electric organ homogenate. RESULTS: Mercury inhibition presents different kinetic behaviors for both enzyme substrates: noncompetitive to choline and of mixed type to AcCoA, with inhibition constants on the order of 0.5 to 1.0 microM. The enzyme activity was recovered using 2,3 dimercapto-propanol (BAL), a well-known chelate for sulphydryl groups and metals, which acted as a protecting agent and was able to revert the Hg(2+) inhibition at a concentration of 10 (-6) M. After treatment with this metal and in the presence of 2,3 dimercapto-propanol, 70% of the enzyme activity was recovered for AcCoA and 80% for choline. CONCLUSIONS: The observed inhibition is likely due to direct protein interaction, because the addition of BAL reversed the effects of HgCl(2) on ChAT activity. The results cast new light on the mechanisms of mercurial neurotoxicity.

Animals↗

Drug evaluation: BAL-8557--a novel broad-spectrum triazole antifungal.

Basilea Pharmaceutica is developing BAL-8557, a water-soluble prodrug of the triazole BAL-4815, for the potential treatment of fungal infections. By August 2005, a phase II study in oral candidiasis was underway. In September 2005, phase III trials were planned for invasive Candida and mold infections, including aspergillus and zygomycetes.

Animals↗

[Impact of co-expression of CD80, CD86 and CD137L genes on tumor immunogenicity in HCC H22-BAL b/c mouse model].

OBJECTIVE: To understand the influence of co-expression of CD80, CD86 and CD137L genes on tumor immunogenicity in hepatocellular carcinoma H22-BAL B/c mouse models. METHODS: The mice were randomly divided into five groups, named A, B, C, D and E, and control groups A and B, 20 mice in each group. Hepatocellular carcinoma H22-BAL B/c mouse model was established by subcutaneous injection of cells H22-Wt, H22-neo, H22-CD80/CD86+, H22-CD137L+ and H22-CD80/CD86/CD137L+, respectively. The rate and incubation period of tumor development, survival rate, and the tumor growth in vivo were observed and recorded. The effects of gene transduction on immunogenicity of the tumor and antitumor immunity of the animals were assessed by re-innoculation of wild type H22 cells. RESULTS: The rate of tumor development in group E was only 50%, much lower than that in other four groups (P < 0. 01). The tumor growth in group C was reduced with complete tumor regression in two hosts (20%, 2/10). In group E, there was more pronounced reduction of tumor size. The maximal tumor sizes were remarkably smaller than those of group C, and there was complete tumor regression in three mice (60%, 3/5). No tumor regression was found in the other three groups. Survival rates of group C and E were significantly higher than that of animals in groups A, B and D (P < 0. 01), but no significant difference was seen between group C and E. The results of re-inoculation test showed that tumor formation rate was 40% (4/10) in group C, 100% (8/8) in group D, and 0 (0/5) in group E. There were significant differences between groups C and E and control group, between group E and C, but not between C and D. After the third time of re-inoculation with H22-Wt cells at the 56th day, tumor occurred in 6/6 mice (100%) of group C, but 0 (0/5) in group E. The difference was very significant. Five animals without tumor formation after the first inoculation in group E, were re-inoculated with H22-Wt cells on the 21st day and the third re-inoculation on the 56th day, no tumor was found (0/5). CONCLUSION: Both co-expression and solo-expression of CD80+ CD86 and CD137L genes reduce the tumorigenicity of wild type H22 cells, but co-expression of CD80, CD86 and CD137L genes can more significantly improve the immunogenicity of H22-CD80/CD86/CD137L+ cells.

4-1BB Ligand↗

[Subpopulations of T lymphocytes in bronchoalveolar lavage (BAL) fluid of different interstitial lung diseases].

Immunocytochemical examinations using the PAP method with monoclonal antibodies against lymphocytes T (CD3, CD4, CD8) were carried out in 31 BAL's from patients with different interstitial lung diseases. A distinct increase of the CD4 (T "helper"): CD8 (T "suppressor") ratio was found in patients with sarcoidosis and in a patient with pigeon breeder's disease. A profound decrease of the CD4/CD8 ratio was found in HIV positive patients. The authors also discussed the methodological problems of correct typing of T cells in BAL.

Bronchoalveolar Lavage Fluid↗

[Preliminary evaluation of the diagnostic usefulness of bronchoalveolar lavage (BAL) in selected cases of interstitial lung diseases].

Diagnostic usefulness of BAL was assessed in 25 selected cases of interstitial lung diseases. There were 14 cases of allergic alveolitis, 6 cases of idiopathic pulmonary fibrosis and one case each of sarcoidosis, lymphangiomyomatosis, granulomotosis bronchocentrica, lymphogranulomatosis maligna, alveolitis of unknown etiology. BAL was assessed diagnostically usefull in 77% of the cases. More helpful was medical history which proved to be useful in all cases, and pulmonary function tests which were helpful in 84%. Lung biopsy was diagnostic in 66.6% of the cases, TBLB in 36.5%, while open lung biopsy carried out in 6 patients was diagnostic in 100%. Bronchoalveolar lavage is a useful element of diagnostic evaluation in patients with interstitial lung disorders, it is a safe method and well tolerated by the patients.

Adult↗

Usefulness of a multiple biomarker assay in bronchoalveolar lavage (BAL) and serum for the diagnosis of small cell lung cancer.

To evaluate the diagnostic usefulness of simultaneous determinations of carcinoembryonic antigen (CEA), neuron specific enolase (NSE), chorionic gonadotrophin (HCG) and carbohydrate antigenic determinant 19-9 (CA 19-9), we studied 48 patients with small cell lung carcinoma (SCLC) and 15 with nonmalignant lung disease. The combination of CEA-BAL, NSE-BAL, and NSE-serum taken together with results of bronchoscopy (histologic and cytologic) showed the highest discriminating power between malignant (SCLC) and nonmalignant lung disease. The sensitivity of bronchoscopy alone was 35%. However, when bronchoscopy results were combined with 3 positive markers, the sensitivity increased to 71%, with at least 2 positive markers to 94%, and with at least 1 positive marker to 100%. When both bronchoscopy and all 3 markers were negative, the results showed a negative predictive value of 100%.

Adult↗

Differences in BAL fluid variables in interstitial lung diseases evaluated by discriminant analysis.

The aim of this study was to investigate the possibility of distinguishing between patients with similarities in clinical presentation, suffering from three frequently occurring interstitial lung diseases, by means of discriminant analysis, using a number of selected variables derived from bronchoalveolar lavage fluid (BALF) analysis. The study involved all 277 patients, who had an initial bronchoalveolar lavage (BAL) in the period 1980-1990. These patients belonged to the following diagnostic groups: sarcoidosis (n = 193), subacute extrinsic allergic alveolitis (EAA) (n = 39) and idiopathic pulmonary fibrosis (IPF) (n = 45). Thirty healthy volunteers were used as controls. Cellular and non-cellular constituents of BALF were evaluated. Variables, which could be used to discriminate among the three diagnostic groups were: yield of recovered BALF, total cell count, and percentages of alveolar macrophages, lymphocytes, polymorphonuclear neutrophils, eosinophils and plasma cells in BALF. When the set of data used to predict the membership of patients to diagnostic groups (test set) was the same as that in which the discriminant analysis was performed (learning set), 93% of the cases were correctly classified. This percentage decreased to 90%, however, when the test set was different from the learning set. It is possible to discriminate among patients with sarcoidosis, EAA or IPF with these selected variables. It appears that bronchoalveolar lavage (BAL) is useful as an adjunct in concert with other diagnostic methods.

Adolescent↗

Inhalation challenge in pigeon breeder's disease: BAL fluid changes after 6 hours.

The purpose of this study was to determine the cellular events occurring 6 h after bronchial inhalation challenge, in a group of pigeon breeders. Twelve subjects agreed to undergo challenge, either with nebulized pigeon serum (Ps) (n = 10), or with saline (n = 2). The development of characteristic symptoms was used to detect a positive response in combination with monitoring tests (white blood cell count (WBC), body temperature, and spirometry). An initial bronchoalveolar lavage (BAL) was performed before inhalation challenge, and a further BAL on the previously spared right middle lobe subsegment or lingula 6 h after challenge. Paired bronchoalveolar lavage fluid (BALF) samples were analysed for urea, albumin, total and differential WBC, interleukin-1 and interleukin-2. There was a significant increase in total cells, lymphocytes, T-lymphocytes, and neutrophils; numbers.ml-1 of BALF in responders. A monitoring score reflecting severity of patient response correlated with an increase in all cell types (p < 0.05). In conclusion, responders developed both a BALF lymphocytic and neutrophilic "alveolitis" following inhalation challenge, the degree of BALF "alveolitis" correlating with the severity of patient response.

Adult↗

BAL lymphocyte activation antigens and diffusing capacity are related in mild to moderate pulmonary sarcoidosis.

To investigate the relationship [corrected] between immunocytological features of bronchoalveolar lavage (BAL) and clinical indices in sarcoidosis, we studied the lymphocyte subsets, as well as the expression of human leucocyte antigen-DR (HLA-DR) and interleukin 2 receptor (IL-2R) antigens in BAL lymphocytes. We studied 16 patients with untreated sarcoidosis and 12 control subjects. We found significantly higher absolute numbers of lymphocytes bearing the IL-2R antigen in sarcoidosis. A stronger difference between groups was observed in both the percentage and absolute numbers of HLA-DR+ lymphocytes. We also found a moderate but significant correlation between the number of lymphocytes expressing the activation antigens and single breath carbon monoxide diffusing capacity in patients with sarcoidosis: DLCO vs HLA-DR+ lymphocytes (r = -0.60); DLCO vs IL-2R+ lymphocytes (r = -0.62); carbon monoxide transfer coefficient (KCO vs HLA-DR+ lymphocytes (r = -0.53); and KCO vs IL-2R+ lymphocytes (r = -0.58). Our results suggest that the reduction in diffusing capacity, expressed as either DLCO or KCO, results from the severity of alveolitis in mild to moderate sarcoidosis.

Adult↗

The mechanism of bronchial hyperreactivity in allergic rhinitis patients. A light microscopic study on BAL and bronchial biopsy.

Epidemiological data indicated that allergic rhinitis often coexists with and may precede the development of reactive airway disease. In particular, ARP with BHR are more likely to develop asthma. However, the pathogenesis of BHR associated with allergic rhinitis is still remains uncertain. Therefore we designed the study on ARP with/without BHR. The aim of this study were to investigate the presence of an inflammatory process in lower respiratory tract in ARP and to relate these changes to airway responsiveness Eleven ARP with BHR (Group I), eleven ARP without BHR (Group II) and two control patients (Control group) were studied. All of the ARP were judged atopic on the basis of positive skin prick test to common inhalant allergens. Bronchial challenges were performed with increasing concentration of M. All the subjects underwent fiberoptic bronchoscopy, BAL and bronchial biopsies were obtained for pathologic examination. The mean total cell and the mean percentage of macrophages, lymphocytes, neutrophils and eosinophils in BAL fluid were in normal range in all groups without any significant differences between the groups. There weren't any correlation between PC20 to M and the total cell counts and percentage counts of these cells. In bronchial biopsy samples, the absolute numbers of lymphocytes, neutrophils, eosinophils and mast cells in the submucosa showed no differences between the three groups. The epithelial shedding was more extensive in ARP than control subjects (p = 0.05). The thickness of the epithelium was prominent in Group I (p < 0.05) but there was no significant differences in the basement membrane thickening between the three groups. We could only find an inverse correlation between PC20 to M and the mast cell counts in the submucosa (r xy:-0.815 p < 0.05). In conclusion, we couldn't observe any prominent morphological changes which indicate that may cause of BHR in ARP except the increased epithelial shedding in Group I. However, the increased epithelial shedding is not a reliable criterion to comment because of the possibility of mechanical damage of bronchial biopsies caused by the forceps.

Adolescent↗

[The effect of fiberoptic bronchoscopy and bronchoalveolar lavage (BAL) on results of spirometric measurements].

The effect of fiberoptic bronchoscopy and bronchoalveolar lavage on the functioning of the respiratory system was studied in 72 patients (42 males and 30 females). The bronchoscopy was performed in the sitting position. Supplemental oxygen was not given to all the evaluated patients. The group included 24 patients with lung cancer, 9 with sarcoidosis, 12 with tuberculosis, 1 with farmer's lung and 10 with other lung diseases (pneumonia, COPD). A control group consisted of 16 patients who were undergoing routine diagnostic endoscopy but who were seen to be without lung disease. Group BF (39 individuals) received only a bronchoscopic examination, group BF+BAL (33 persons) received a bronchoscopy followed by BAL using 140 ml. of normal saline solution as a lavage fluid. After the bronchoscopic examination there were significant differences in all spirometric measurements, except MEF25. The bronchoscopy and bronchoalveolar lavage caused a transient fall in FEV1, VC, MEF50, MEF75 (7.7-9.4%) which was similar in both groups. These measurements returned to normal after 24 hours. The testing of pulmonary functioning before the bronchoscopy was seen to be clinically important for safety of the patient undergoing this procedure.

Adult↗

[A case of multifocal Langerhans cell granulomatosis: a BAL follow up study].

Langerhans cell granulomatosis, once called histiocytosis X, is a rare disease. A case of multifocal Langerhans cell granulomatosis in the bone, lymph nodes, skin and lungs of an 18-year-old man is described. Head CT and MRI showed a soft tissue mass of the left temporal bone. Lymph node and skin biopsies substantiated a diagnosis of Langerhans cell granulomatosis. A High resolution CT scan of the lung revealed a small cystic lesion, and bronchoalveolar lavage (BAL) showed an increased number of S-100 positive cells. Steroid therapy resulted in complete resolution, and no S-100 positive cells were obtained in the follow-up BAL study.

Adolescent↗

N-acetyl-beta-D-glucosaminidase activity within BAL from macaques exposed to generic coal dusts.

N-acetyl-beta(beta)-D-glucosaminidase is a lysosomal enzyme secreted by alveolar macrophages in response to phagocytosis of particulate material. Alveolar macrophages participate in the degradation and fibrosis of pulmonary tissue that results in pneumoconiosis. Known quantities of four characterized respirable dusts were bronchoscopically placed into the right caudal lung lobe of macaque monkeys. Bronchoalveolar lavage (BAL) samples were collected from dust-exposed right lung and unexposed left lung of the same individuals at 2-week intervals for 12 weeks after dust instillation. The samples were tested for N-acetyl-beta-D-glucosaminidase activity to determine if the enzyme levels could serve as an indicator of pulmonary injury induced by generic coal dusts when compared to known fibrogenic and nuisance dusts. Installation of generic quartz, anthracite, or TiO2 dusts produced significant elevations of enzyme activity and increased numbers of macrophages in the dust-exposed lobes. Elevations in enzymatic activity and macrophage numbers were greatest in response to generic quartz dust. These results suggest that quantitative levels of N-acetyl-beta-D-glucosaminidase activity may be a useful indicator of acute and chronic lung injury following exposure to fibrogenic and nonfibrogenic dusts.

Acetylglucosaminidase↗

Excision of chromosomal DNA loops by treatment of permeabilised cells with Bal 31 nuclease.

The specificity of long-range fragmentation of human nucleolar genes by Bal 31 nuclease was studied using fractionation of cleavage products by pulsed field gel electrophoresis, followed by Southern hybridization. It was found that limited treatment of permeabilised cells with this nuclease results in accumulation of DNA scissions in matrix attachment areas. Consequently, chromosomal DNA loops and their oligomers are released from the genome.

Cell Line↗

Identification of acyl phosphatidylglycerol as a minor phospholipid of Pseudomonas BAL-31.

Compound X, a minor phospholipid of Pseudomonas BAL-31 and bacteriophage PM2, has been identified as X-3-phosphatidyl-1'-(3'-acyl)-glycerol, or acyl phosphatidylglycerol. The water-soluble product obtained by mild alkaline hydrolysis showed the same RF value as that of glycerophosphoryl-glycerol. The chemical analysis gave the ratio 1 : 3 : 2 for phosphate-acyl ester-glycerol. The position of the third acyl group was determined by nuclear magnetic resonance techniques.

Bacteriophages↗

Stereoconfiguration of phosphatidylglycerol in the membrane of bacteriophage PM2 and in its host, Pseudomonas BAL-31.

Turnover of the acylated and unacylated glycerol moieties of phosphatidylglycerol was examined during infection of Pseudomonas BAL-31 by bacteriophage PM2. No turnover of either glycerol moiety was observed in infected or inunfected cells. The stereochemical configuration of phosphatidylglycerol from both virus and host was determined and proved to be 3-sn-phosphatidyl-1'-sn-glycerol. These results exclude a mechanism of mobilizing lipids for the virus by acylation and deacylation of 3-sn-phosphatidyl-1'-sn-glycerol in the host membrane to form 1-sn-phosphatidyl-3'-sn-glycerol in the membrane of PM2.

Bacteriophages↗