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Biomedical subjects

F Ogushi

Publications and source records attributed to F Ogushi.

At least 55 records · Page 3Linked to original sources
PubMed1993

[Neutrophil chemotactic factor in supernatant from pulmonary fibroblasts stimulated with cytokines].

Fibroblasts are important for maintenance of the structural frame network for most tissues, and they also play an important role in the inflammatory process via production of various mediators. In this study, we demonstrated that pulmonary fibroblasts may participate in pulmonary inflammation by production of neutrophil chemotactic factor (NCF). Pulmonary fibroblasts were stimulated with various cytokines (IGF-1, PDGF, IL-1 alpha, IL-1 beta, IL-2, IL-6, TNF, IFNr). Fibroblasts stimulated with either TNF, IL-1 alpha or IL-beta but not IGF, PDGF, IL-2 or IL-6 demonstrated a kinetic and dose-dependent increase in NCF activity. The NCF activity of crude supernatant was heat-stable and was not changed by anti-C5 antibody treatment or ether extraction. Characterization of the NCF activity by gel-filtration using high pressure liquid chromatography showed two active fractions, one with MW greater than 100 kD and the other with MW less than 10 kD. NCF activity in the small molecular weight fraction was demonstrated by inhibition of chemotaxis by addition of anti-IL-8 antibody. These data suggest that cytokine-treated fibroblast-derived NCF may be important in the pathogenesis and expression of a variety of pulmonary disease processes associated with neutrophil accumulation and activation.

Cytokines↗
PubMed1992

Neutrophil chemotactic factors in the respiratory tract of patients with chronic airway diseases or idiopathic pulmonary fibrosis.

This study was designed to clarify the contributions of specific neutrophil chemotactic factors (NCF) in neutrophil accumulation in the human respiratory tract associated with various diseases. The activity and characteristics of the NCF in the bronchoalveolar lavage (BAL) fluid and culture media of alveolar macrophages obtained from normal volunteers, control patients, patients with chronic airway diseases (CAD) and patients with idiopathic pulmonary fibrosis (IPF) were examined. The BAL fluid from normal volunteers contained NCF comparable with the chemotactic factors interleukin-8 (IL-8) and leukotriene B4 (LTB4). Analysis of the biochemical characteristics of NCF released from alveolar macrophages suggests that they are derived from alveolar macrophages. The NCF activities in BAL fluids from patients with CAD and IPF were higher than those in BAL fluids from normal volunteers and control patients. Biochemical analysis demonstrated that several kinds of NCF, including those derived from the complement component C5 and alveolar macrophages, were present in the BAL fluid from patients with CAD and respiratory infections. The especially marked increase of C5-derived NCF indicate their importance in neutrophil accumulation in the respiratory tract of patients with CAD. Alveolar macrophages released different types of NCF after different lengths of culture periods (4 h and 24 h). Alveolar macrophages from patients with IPF released larger amounts of NCF than alveolar macrophages from normal volunteers, indicating the importance of alveolar-macrophage-derived NCF as well as C5-derived NCF in neutrophil accumulation in the respiratory tract of patients with IPF. These results suggest that various types of NCF increase in response to different disease states of the respiratory tract and serve to regulate the accumulation of neutrophils.

Adult↗
PubMed1992

Differential cell analysis in bronchoalveolar lavage fluid from pulmonary lesions of patients with tuberculosis.

To obtain information on the cellular reactions to Mycobacterium (M) tuberculosis in the lung, we analyzed the cells in bronchoalveolar lavage (BAL) fluid from pulmonary lesions in comparison with those in BAL fluid from nonaffected regions of the lungs, and control lungs, and in peripheral blood of patients with tuberculosis. Neutrophils and lymphocytes were increased in number in BAL fluid from affected lesions of the lungs of patients with miliary tuberculosis and patients with active pulmonary tuberculosis compared with those in BAL fluid from control patients, but the number of alveolar macrophages was decreased in BAL fluid from tuberculous lesions. However, the numbers of these cells were not changed in the BAL fluid from nonaffected regions of the lungs of patients with active or inactive pulmonary tuberculosis. The numbers of lymphocytes were decreased and the numbers of monocytes were increased in peripheral blood from patients with miliary tuberculosis and with active tuberculosis, indicating inverse changes in the numbers of lymphocytes and monocytes in the peripheral blood to those in the BAL fluid of patients with tuberculosis. These results indicate characteristic redistributions of immune or inflammatory cells in response to infection with M tuberculosis and suggest that these changes are important for understanding the pathophysiology of pulmonary tuberculosis.

Adult↗
PubMed1992

[Measurement of CA19-9 in bronchial lavage fluid from patients with lung cancer].

Carbohydrate antigen 19-9 (CA19-9) was measured in bronchial lavage fluid in 21 patients with lung cancer and 4 patients with benign lung diseases (2 patients with DPB, 2 patients with BE). Bronchial lavage of the tumor-related bronchus was performed. In normal subjects, levels of CA19-9 in lavage fluid were less than 1000 IU/ml. On the other hand, in 6 patients with lung cancer, levels of CA19-9 were higher than 1000 IU/ml, and in 3 of these cases, CA19-9 levels were higher than 8000 IU/ml. All six three cases were histologically diagnosed as adenocarcinoma. Tumor resected at operation was then stained by antibody recognizing CA19-9. Tumor in cases with high levels of CA19-9 was stained immunohistochemically. These results indicate that measurement of CA19-9 in bronchial lavage fluid of the tumor-related bronchus is a useful auxiliary method in the diagnosis of lung cancer.

Adenocarcinoma↗
PubMed1992

Interleukin-4 as a potent down-regulator for human alveolar macrophages capable of producing tumour necrosis factor-alpha and interleukin-1.

The effects of recombinant human interleukin-4 (IL-4) on the production of interleukin-1 (IL-1) and tumour necrosis factor-alpha (TNF alpha) by human alveolar macrophages (AM) and autologous peripheral blood monocytes (PBM) in response to lipopolysaccharide (LPS) were examined. AM and PBM were obtained by bronchoalveolar lavage and centrifugal elutriation, respectively, from healthy donors. The production of IL-1 (alpha and beta) and TNF alpha by human AM and PBM were quantitated by enzyme immunoassays (EIA). When activated with LPS, AM secreted much more TNF alpha, but less IL-1 beta than PBM. The production of IL-1 (alpha and beta) by activated AM and autologous PBM was suppressed dose-dependently by IL-4. The inhibitory effect of IL-4 was greatest when it was added to AM or PBM simultaneously with LPS or within 3 h after LPS. The suppressive effect of IL-4 was completely neutralized by pretreatment with rabbit anti-IL-4 antiserum. IL-4 also suppressed the production of IL-1 and TNF alpha by monocyte-derived macrophages. As measured by thymocyte co-stimulation assay, the production of cell-associated IL-1 was inhibited by coculture of AM plus LPS with IL-4. Northern blot analysis showed suppression by IL-4 of expression of messenger ribonucleic acid (mRNA) for IL-1 and TNF alpha in LPS-stimulated AM. We conclude that IL-4 is a potent down-regulator for human alveolar macrophages capable of producing IL-1 and TNF alpha.

Adult↗
PubMed1991

Thrombin enhances lung fibroblast proliferation in bleomycin-induced pulmonary fibrosis.

To clarify the role of thrombin in fibroblast growth and the development of pulmonary fibrosis in bleomycin-induced interstitial lung disease, we examined the relationship of thrombin activity to fibroblast growth-stimulating activity (FGA) in bronchoalveolar lavage (BAL) fluid from bleomycin-treated rats. Male Wistar rats were given a single intratracheal injection of bleomycin, BAL was performed 2, 6, and 15 days later, and the BAL fluid was assayed for thrombin activity and FGA. Higher FGA than the control value was detected in the BAL fluid from rats on day 6 after bleomycin administration. In bleomycin-treated rats, thrombin activity in the BAL fluid was significantly elevated on day 2 and maximal on day 6. The FGA of the BAL fluid from bleomycin-treated rats on day 6 was significantly decreased by its treatment with various thrombin inhibitors, such as alpha 1-protease inhibitor, antithrombin III, hirudin, and MD-805. In our assay, purified rat thrombin also showed FGA in vitro, and its FGA was inhibited by the same concentrations of these thrombin inhibitors as those inhibiting the activity in the BAL fluid. On ammonium sulfate fractionation, most of the thrombin activity was recovered in the fraction of 35 to 50% saturation in which most of the FGA was detected. These results suggest that the FGA of the BAL fluid from bleomycin-treated rats was at least partly due to thrombin is responsible, at least in part, for fibroblast growth and pulmonary fibrosis in bleomycin-induced interstitial lung disease.

Ammonium Sulfate↗
PubMed1991

Risk factors for emphysema. Cigarette smoking is associated with a reduction in the association rate constant of lung alpha 1-antitrypsin for neutrophil elastase.

The increased risk of developing emphysema among individuals who smoke cigarettes and who have normal levels of alpha 1-antitrypsin (alpha 1AT) is hypothesized to result from a decrease in the antineutrophil elastase capacity of the lower respiratory tract alpha 1AT of smokers compared with nonsmokers. To evaluate this hypothesis we compared the time-dependent kinetics of the inhibition of neutrophil elastase by lung alpha 1AT from healthy, young cigarette smokers (n = 8) and nonsmokers (n = 12). alpha 1-antitrypsin was purified from lavage fluid using affinity and molecular sieve chromatography, and the association rate constant (k assoc) for neutrophil elastase quantified. The k assoc of smoker plasma alpha 1AT (9.5 +/- 0.5 X 10(6) M-1s-1) was similar to that of nonsmoker plasma (9.3 +/- 0.7 X 10(6) M-1s-1, P greater than 0.5). In marked contrast, the k assoc of smoker lower respiratory tract alpha 1AT was significantly lower than that of nonsmoker alpha 1AT (6.5 +/- 0.4 X 10(6) M-1s-1 vs. 8.1 +/- 0.5 X 10(6) M-1s-1, P less than 0.01). Furthermore, the smoker lower respiratory tract alpha 1AT k assoc was significantly less than that of autologous plasma (P less than 0.01). When considered in the context of the concentration of alpha 1AT in the lower respiratory tract epithelial lining fluid, the inhibition time for neutrophil elastase of smoker lung alpha 1AT was twofold greater than that of nonsmoker lung alpha 1AT (smoker: 0.34 +/- 0.05 s vs. nonsmoker: 0.17 +/- 0.05 s, P less than 0.01). Consequently, for concentrations of alpha 1AT in the lower respiratory tract it takes twice as long for an equivalent amount of neutrophil elastase to be inhibited in the smoker's lung compared with the nonsmoker's lung. These observations support the concept that cigarette smoking is associated with a decrease in the lower respiratory tract neutrophil elastase inhibitory capacity, thus increasing the vulnerability of the lung to elastolytic destruction and thereby increasing the risk for the development of emphysema.

Emphysema↗
PubMed1991

[A case of small cell lung cancer associated with pulmonary sarcoidosis].

A 63-year-old man with pulmonary sarcoidosis, diagnosed by mediastinal lymph node biopsy in 1977, was admitted in Feb. 1987 because of shortness of breath and cough. Chest X-ray showed bilateral hilar lymphadenopathy and a tumor shadow in the right lung field. Histological examination of specimens biopsied from the right lung revealed small cell carcinoma (S.C.C.). Bronchoalveolar lavage was performed to evaluate the disease activity of sarcoidosis, and the total number of cells and T-lymphocytes; the ratio of CD4+ cells to CD8+ cells was not increased. He was treated with combination chemotherapy, however, he died of respiratory failure after 7 months. An autopsy was performed, and the lesions were examined histologically. The sarcoid lesion in a lymph node obtained at autopsy was not active, in contrast to that obtained by mediastinal lymph node biopsy. Lung cancer and sarcoidosis are both common diseases, but their coexistence in the same patient is not common, and autopsied cases are rare. In this case, an autopsy was performed, and BAL had been performed prior to his death. The relationship between the BAL findings and the histology of sarcoidosis was examined. Based on the results of autopsy and BAL, the sarcoidosis was inactive prior to death, but had been histologically active 10 years previously. Therefore, this is a very interesting case, since we can examine the relationship between the two diseases, and the progression of each disease. This case also provides an interesting example of differentiation of sarcoidosis from S.C.C. Metastatic invasion of the hilar lymph nodes without bronchial stenosis and changes secondary to stenosis may often occur in patients with small cell lung cancer. Such metastatic invasion closely resembles the bilateral hilar lymphadenopathy of sarcoidosis; therefore, in some cases, it may be extremely difficult to differentiate the two diseases.

Bronchoalveolar Lavage Fluid↗
PubMed1991

[The role of thrombin on lung fibroblast growth and fibrosis in bleomycin-induced lung disorder].

In order to clarify the role of thrombin on the development of pulmonary fibrosis in diffuse interstitial lung diseases, we examined the relationship between fibroblast growth-stimulating activity (FGA) and thrombin activity in bronchoalveolar lavage fluid (BALF) from rats with bleomycin-induced interstitial lung disorders. Male Wistar strain rats (body weight about 200 g) were given a single intratracheal injection of 0.9 mg bleomycin, and bronchoalveolar lavage was performed on days 2, 6 and 15. The BALF was centrifuged at 250 X g for 10 min to remove cells, and then the supernatant was recentrifugation at 27,000 X g for 40 min to remove pulmonary surfactants. The supernatant (10 ml) was dialyzed overnight against distilled water, frozen at -70 degrees C, freeze-dried, and resuspended in 2 ml of Dulbecco's modified Eagle medium (concentrated 5-fold). The 5-fold concentrated BALF was added to rat lung fibroblast culture media, and assayed for cytotoxic activity and FGA. Thrombin activity in 250 X g supernatant was measured by using fluorescence assay with the synthetic peptide substrate, Boc-Val-Pro-Arg-4-methylcoumaryl-7-amide. Histological examination showed a prominent increase in fibroblast number in the pulmonary interstitium on day 6, and transformation of fibroblasts into mature forms, fibrocytes, on day 15. On day 2 after bleomycin administration, no FGA was seen but cytotoxic activity was detected in the BALF. On day 6, the cytotoxic activity was not found, whereas FGA showed a significantly higher level than the control value. On day 15, the FGA decreased to the control value.(ABSTRACT TRUNCATED AT 250 WORDS)

Ammonium Sulfate↗
PubMed1991

[A case of metastatic rib tumor from thyroid cancer confirmed by the presence of thyroglobulin].

A 63-year-old female, with a chief complaint of right chest pain was referred to our hospital because of an abnormal right chest wall shadow on chest X-ray. A rib tumor was suspected based on her chest CT scan. Percutaneous needle biopsy yielded a diagnosis of well-differentiated adenocarcinoma. As metastatic rib tumor was suspected, the primary tumor was sought for. A thyroid gland nodule was recognized by ultrasonography, and the cytological diagnosis was class V. Immunohistological demonstration of the thyroglobulin studies of the rib tumor tissue revealed papillary and trabecular patterns of cell arrangement and the presence of thyroglobulin existence. Definitive diagnosis of metastatic rib tumor from thyroid cancer was established. Immunohistological examination is useful to confirm the diagnosis of metastatic cancer of thyroid origin.

Adenocarcinoma↗
PubMed1991

[C5 contents and neutrophil chemotactic activities in bronchiolar and alveolar regions].

To clarify the localization and mechanism of neutrophil infiltration in the lower respiratory tract, we measured neutrophil number, neutrophil chemotactic factor (NCF) activity and content of C5 in bronchial lavage (BL) fluid and bronchoalveolar lavage (BAL) fluid. Numbers of neutrophils, NCF activity and C5 content were higher in the BL fluid from normal volunteers (NV) and control patients (CP) than those in the BAL fluid from the same subjects. The NCF activity in the BL fluid was inhibited approximately 40% by anti-C5 antiserum, and correlated with C5 content in the BL fluid. In the BAL fluids of patients with chronic airway diseases (CAD) and patients with idiopathic interstitial pneumonia (IIP), neutrophil number, NCF activity and C5 content were increased compared to those in BAL fluid from NV or CP. These results indicated that neutrophils are predominant in the bronchial region compared to the alveolar region, and that C5-derived NCF play important roles in the accumulation of neutrophils in the bronchial region. Also C5-derived NCF are thought to be related to, at least, a part of the neutrophil infiltration in the respiratory tract of patients with CAD and IIP.

Adult↗
PubMed1990

[Lung surfactant apoprotein (LSP) content of sputum samples from patients with chronic airway diseases].

LSP contents of sputum samples from patients with chronic airway diseases were measured by an enzyme-linked immunosorbent assay (ELISA) kit which was designed by Kuroki et al to examine whether a substance identical to lung surfactant contained in alveolar lining layer, is also contained in respiratory tract fluid or not in the ELISA kit. One antibody to LSP was conjugated to peroxidase and another one to LSP was fixed onto a bead. A neo-anionic detergent, Triton X-100 and an anionic detergent, sodium dodecyl sulfate (SDS) were added to extraction medium to separate LSP from lung surfactant, and LSP reaction of sputum sample was maximal when the ratio of Triton X-100 to SDS was in range of 1 to 4. Airway mucous glycoprotein (AMG) purified from sputum sample did not show any LSP reaction. In CsCl density gradient ultracentrifugation of whole sputum, the LSP reaction was detectable only in the top fraction with density of about 1.40 and AMG was located in the fraction with a density of about 1.50. These results indicate that the LSP reaction of sputum sample is not due to false reaction caused by nonspecific binding of viscous AMG to the two antibodies to LSP, but to the existence of LSP. Therefore it was concluded that lung surfactant is contained in respiratory tract fluid. In general, the LSP concentrations in sputum samples were lower in purulent sputa than in mucoid or mucopurulent sputa, and lower in patients with diffuse panbronchiolitis and bronchiectasia than in those with pulmonary emphysema and chronic bronchitis. It was shown that LSP was hydrolyzed by neutrophil leucocyte homogenate. These results suggest that LSP content of sputum is influenced by various factors such as infection and disease in the respiratory tract, and thus is useful to estimate pathological states of chronic airway diseases.

Aged↗
PubMed1989

A case of bronchogenic cyst with high production of antigen CA 19-9.

A 35-year-old man was hospitalized with complaints of retrosternal pain and high fever. A chest radiograph showed a large round mass in the mediastinum. Of the several tumor markers in the serum tested, only CA 19-9 was elevated. Thoracotomy revealed a cystic mass with purulent hemorrhagic materials. Histologically the cyst was lined by bronchial epithelium with no evidence of malignancy. The high level of CA 19-9 in the cystic fluid, and positive immunohistochemical staining of the bronchial glands in the cyst wall for CA 19-9 indicated that the elevated serum level of CA 19-9 originated from the bronchogenic cyst after its infection.

Adult↗
PubMed1988

Characterization of the gene and protein of the alpha 1-antitrypsin "deficiency" allele Mprocida.

The "deficiency" group of alpha 1-antitrypsin (alpha 1AT) alleles is characterized by alpha 1AT genes that code for alpha 1AT present in serum but in amounts insufficient to protect the lower respiratory tract from progressive destruction by its burden of neutrophil elastase. Mprocida, a rare alpha 1AT allele associated with alpha 1AT serum levels less than 10 mg/dl (normal 150-350 mg/dl), codes for an alpha 1AT molecule that focuses on immobilized pH gradient isoelectric gels slightly cathodal to the common normal M1 (Val213) protein. On a per molecule basis, Mprocida has a mildly reduced function as an inhibitor, with an association rate constant for human neutrophil elastase of 7.0 +/- 0.1 x 10(6) M-1 s-1 (normal M1 (Val213) 9.3 +/- 0.8 x 10(6), p less than 0.01). The Mprocida molecule behaves normally in vivo with a half-life similar to normal M1 alpha 1AT molecules. Restriction endonuclease mapping demonstrates that the cloned Mprocida gene was grossly intact. Sequencing of all the exons, exon-intron junctions, and the major promoter region demonstrated Mprocida to be identical to the M1 (Val213) gene except for a single base substitution in exon II coding for amino acid 41 of the mature protein (M1 (Val213) Leu41 CTG----Mprocida Pro41 CCG). Usefully, the coding sequence of the alpha 1AT residues 40-41 is recognized by the restriction endonuclease PvuII so that using a probe corresponding to this region of exon II, the Mprocida mutation can be rapidly identified by Southern analysis. Evaluation of the crystallographic structure of alpha 1AT suggests the Leu41 to Pro41 mutation may disrupt alpha-helix A in the region of Pro21-Ser45, suggesting the possibility that the alpha 1AT Mprocida molecule is unstable and degraded intracellularly prior to secretion.

Alleles↗
PubMed1988

Evaluation of the S-type of alpha-1-antitrypsin as an in vivo and in vitro inhibitor of neutrophil elastase.

S-type alpha 1-antitrypsin (alpha 1AT) is a deficiency haplotype that differs from the common normal M1 (val213) alpha 1AT haplotype by a single amino acid (glu264 to val264). To evaluate the adequacy of the antineutrophil elastase protection associated with the S homozygous state, alpha 1AT plasma and lung epithelial lining fluid (ELF) levels and antineutrophil elastase function were analyzed in 9 PISS subjects. The plasma alpha 1AT levels of SS subjects were intermediate between that of M1M1 and ZZ subjects (p less than 0.001, all comparisons) and the plasma neutrophil elastase inhibitory capacity paralleled the differences in alpha 1AT concentration (p less than 0.001, all comparisons). The association rate constant for neutrophil elastase of the purified S protein was less than that of the normal molecule (S-type, 7.1 +/- 0.1 X 10(6) M-1 s-1; M1-type, 9.6 +/- 0.2 X 10(6) M-1 s-1; p less than 0.001), but much greater than that for the Z molecule (p less than 0.001). Exposure of the purified S protein to increasing oxidant burdens resulted in a dose-dependent reduction in the ability of the molecule to inhibit neutrophil elastase in a fashion parallel to that of the M1 and Z proteins. Quantification of ELF alpha 1AT levels and antineutrophil elastase capacity demonstrated that the SS ELF parameters were, as in plasma, intermediate between M1 homozygotes and Z homozygotes. Using the association rate constant together with the quantification of ELF alpha 1AT levels, the "in vivo lung inhibition time" was estimated, yielding an assessment of the relative antineutrophil elastase screen of the PISS lower respiratory tract.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Characterization of the gene and protein of the common alpha 1-antitrypsin normal M2 allele.

The normal M2 variant of alpha 1-antitrypsin (alpha 1AT) was cloned from a genomic DNA library of an individual homozygous for this allele. Sequencing of all coding exons of the M2 gene revealed it was identical to the common M1(Val213) gene except for two bases (M1(Val213) CGT Arg101, M2 CAT His101; M1(Val213) GAA Glu376 M2 GAC Asp376). Analysis of the sequence of the M1(Val213) and M2 genes around residue 101 revealed the M1 Arg101----M2 His101 caused a loss of the cutting site for the restriction endonuclease RsaI. Using this enzyme, as well as 19-mer oligonucleotides probes centered at residues 101 and 376, evaluation of genomic DNA from 22 M1 alleles and 14 M2 alleles revealed that residue 101 was Arg in all M1 alleles and His in all M2 alleles, while residue 376 was Glu in all M1 alleles and Asp in all M2 alleles. Despite the differences in sequence at two amino acids, the M1(Val213) and M2 proteins function similarly as assessed by quantification of the association rate constant of each for their natural substrate neutrophil elastase. In the context that there are two mutations separating the M1(Val213) and M2 alleles, it is likely that there is another alpha 1AT variant that was an intermediate in the evolution of these genes.

Alleles↗