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Biomedical subjects

S Kohno

Publications and source records attributed to S Kohno.

At least 415 records · Page 23Linked to original sources
PubMed1997

Analysis of T cell subsets and beta chemokines in patients with pulmonary sarcoidosis.

BACKGROUND: Sarcoidosis is a systemic granulomatous disorder of unknown origin characterised by accumulation of T lymphocytes and macrophages in multiple organs. Several cytokines and adhesion molecules may contribute to the accumulation of T lymphocytes in pulmonary sarcoidosis. The distribution of T lymphocyte subsets, T cell bearing CD11a and beta chemokines such as regulated on activation normal T expressed and secreted (RANTES), macrophage inflammatory peptide 1 alpha (MIP-1 alpha), and macrophage chemoattractant protein 1 (MCP-1) in bronchoalveolar lavage (BAL) fluid and peripheral blood were compared in untreated patients with sarcoidosis and normal subjects. METHODS: Flow cytometric analysis with monoclonal antibodies to cell surface antigens was used to identify T lymphocyte subsets in the BAL fluid of untreated patients with sarcoidosis (n = 40)--either without (group A, n = 12) or with (group B, n = 28) radiological evidence of pulmonary involvement--and in 22 normal subjects. The level of different beta chemokines was estimated by enzyme linked immunosorbent assay (ELISA). RESULTS: A high percentage of CD3+ cells, CD4+ cells expressing HLA-DR antigen, and a high CD4/CD8 ratio were detected in the BAL fluid of patients compared with normal subjects. In particular, CD4+ CD29+ memory T cells were significantly increased in patients with sarcoidosis. Furthermore, these cells were higher in those in group B than group A. The level of RANTES in the BAL fluid of patients was significantly higher than in normal subjects and correlated well with the percentage, number, and expression of CD29 on CD4 cells. The expression of CD11a (alpha chain of lymphocyte function associated antigen-1, LFA-1) on CD3+ cells in the BAL fluid of patients with sarcoidosis was not different from that of normal subjects. However, the expression of CD11a on CD3+ cells in the BAL fluid of patients in group A was significantly lower than that of patients in group B and normal subjects. CONCLUSIONS: These results suggest a possible interaction between activated memory T cells bearing CD11a and RANTES which may contribute to the pulmonary involvement in patients with sarcoidosis.

Adult↗
PubMed1997

Effect of clarithromycin on lymphocytes in chronic respiratory Pseudomonas aeruginosa infection.

In a newly established murine model of chronic Pseudomonas aeruginosa respiratory infection mimicking diffuse panbronchiolitis (DPB), we investigated the effect of oral administration of clarithromycin on lymphocyte accumulation in the lung. Infection was produced by placement of a plastic tube precoated with P. aeruginosa in the bronchus. The number of bacteria on the tube was 6.25 +/- 0.22 log10 colony-forming units (cfu)/ml. Viable bacteria were constantly isolated at 10(5) to 10(6) cfu/specimen from the lungs for more than 1 yr. The histopathologic features resembled those of DPB consisting of massive accumulation of lymphocytes in the lung. The total number of pulmonary lymphocytes started to increase on Day 7, reaching a peak level within 12 d of intratracheal challenge. The number remained steady at that level for up to 120 d. There was also a steady fall in the CD4+/CD8+ ratio in the lungs, commencing on Day 7 and persisting to Day 120. A 10-d course of oral clarithromycin (10 mg/kg/d) from Day 7 resulted in a reduction of lymphocyte numbers to baseline level, although the dose did not influence the number of bacteria in the lungs. Treatment also increased the CD4+/CD8+ ratio to the baseline level from Day 7 to 17. Our results were similar to those detected in bronchoalveolar lavage fluid of patients with DPB and suggest that the therapeutic benefits of clarithromycin are due to its anti-inflammatory properties rather than antimicrobial effect.

Animals↗
PubMed1997

Rapid prediction of rifampin susceptibility of Mycobacterium tuberculosis.

We evaluated the relationship between rifampin (RIF) susceptiblility and amino acid substitution in rpoB gene of Mycobacterium tuberculosis and the usefulness of rpoB gene sequencing in the rapid prediction of RIF susceptibility of M. tuberculosis in clinical specimens. A total of 76 genetic alterations in the 69 bp core region of rpoB gene were detected in 74 of 130 M. tuberculosis strains. Examination of the correlation between the minimum inhibitory concentrations (MICs) of RIF and amino acid substitutions in the 69 bp core region of rpoB gene revealed that all 43 strains containing amino acid substitution with Leu or Trp in codon 531 showed RIF-resistant phenotypes, with MICs > or = 64 microg/ml. In contrast, a variable level of RIF susceptibility was observed among strains containing amino acid substitutions in either codon 516 or codon 526. In the clinical study, we tested 26 sputum samples, two gastric lavages, and one synovial fluid sample obtained from patients with tuberculosis. The RIF susceptibility predicted by direct rpoB sequencing was satisfactorily compatible with the results of the RIF-susceptibility test and the MICs of RIF against isolated organisms. Our results suggest that rpoB gene sequencing is useful for the detection of M. tuberculosis in clinical samples as well as the rapid prediction of RIF susceptibility of these strains.

Amino Acid Sequence↗
PubMed1997

Effect of Japanese angelica root extract on pentobarbital-induced sleep in group-housed and socially isolated mice: evidence for the central action.

We investigated the effect of the aqueous extract of Japanese angelica root (JAR) on pentobarbital (PB) sleep in group-housed and socially isolated mice. The JAR extract (1.25-2.5 g/kg, p.o.) dose-dependently reversed the decrease in PB sleep caused by isolation stress without affecting PB sleep in group-housed mice. The JAR extract (2.5 g/kg, p.o.) also antagonized the decrease in PB sleep caused by the alpha 2-adrenoceptor antagonists yohimbine and idazoxan (1 mg/kg, i.p.) and the alpha 1-adrenoceptor agonist methoxamine (200 nmol, i.c.v.) in group-housed mice. These results suggest that the JAR extract reverses changes in the arousal level caused by isolation stress and the activation of central noradrenergic systems.

Administration, Oral↗
PubMed1997

A new model of experimental allergic rhinitis using Japanese cedar pollen in guinea pigs.

In the majority of the models of experimental allergic rhinitis, antigen challenge has been performed by single topical instillation or perfusion with the solution. The present study was performed to establish a good model using Japanese cedar pollen, which is able to repeatedly induce allergy restricted to the upper airway. Guinea pigs sensitized with the pollen extracts were subjected to quantitative and repeated inhaling of the pollen with a devised apparatus. Following the respective challenges, the nasal cavity was washed with a new technique: Washing with physiologic saline was performed from one nostril to the other one, the latter of which was kept under slightly reduced pressure. When the animal was subjected to cedar pollen inhalation, almost all the pollens inhaled were located in the upper airway. At the 5th inhalation, nasal cavity lavage revealed that both albumin leakage and histamine release into the nasal cavity were increased at maximum levels in 1 hr (respectively 2 mg and 3 ng/animal); and at the same time, a considerable number of leukocytes, especially eosinophils, were found migrating into the nasal cavity for at least 10 hr. The present methods can permit various analyses of allergic rhinitis and the assessment of drugs without sacrificing the animal over the long term.

Albumins↗
PubMed1997

Repeated antigen inhalation-induced reproducible early and late asthma in guinea pigs.

To develop a model of chronic experimental asthma in guinea pigs, the animal was forced to inhale the mist of a low dose of ovalbumin (OA) adsorbed on fine Al(OH)3 for sensitization once every 4 weeks. The animal was challenged by inhalation with the mist of OA on day 14 after the respective sensitizations. Either the first or the second antigen challenge markedly induced an early asthmatic response (EAR), whereas there was hardly any late asthmatic response (LAR). At the 3rd challenge, LAR also emerged with some severity. These dual responses were consistently observed until the 10th challenge. On the other hand, repeated inhalation/challenge, once every 2 weeks, with OA alone at the same dose tended to lead to the desensitization of the EAR. In addition, LAR was hardly observed throughout the experiments. In both groups, gamma 1 and IgE levels in the serum were elevated by the repetitive antigen inhalations, yet no obvious relationship between these antibody levels and the intensity of either EAR or LAR was recognized. The present results indicate that the asthmatic model with reproducible EAR and LAR developed in this study appears to be very beneficial for the investigation of bronchial asthma and for the assessment of anti-asthma drugs.

Administration, Inhalation↗
PubMed1997

Systemic idiopathic fibrosis with inflammatory pulmonary lesions.

Systemic idiopathic fibrosis is characterized by non-suppurative inflammatory diseases of connective tissue, mainly adipose tissue. Although, in this condition, fibrosis may develop in several organs, there have been few reports of fibrosis involving the lung or pleura. We present a case of systemic idiopathic fibrosis associated with inflammatory pulmonary lesions, mimicking lung cancer with multiple pulmonary metastases. Chest CT and MRI showed a spiculated mass around the aortic arch with localized aortic wall thickening and nodules in the lungs. Abdominal CT showed a homogeneous mass around the abdominal aorta, consistent with retroperitoneal fibrosis. Transbronchial lung biopsy of the lesion in the right mid-lung field showed only a few scattered histiocytes accompanying inflammatory and fibrotic change. There was no evidence of malignancy, necrosis, angitis or mycobacterial infection. The lesions almost completely disappeared following prednisone treatment.

Aged↗
PubMed1997

Gamma-delta T cells in BAL fluid of chronic lower respiratory tract infection.

Gamma-delta (gamma/delta) T cells are thought to represent the first line of defense against various pathogenic microorganisms. The aim of the present study was to investigate whether gamma/delta T cells were increased in BAL fluid (BALF) of patients with diffuse panbronchiolitis (DPB), a model of chronic lower respiratory tract infection. The study population consisted of four groups, including patients with DPB, sarcoidosis, idiopathic pulmonary fibrosis, and normal subjects. Two-color direct immunofluorescence and flow cytometry were used for analysis of peripheral blood or BALF from these patients. The percentage of peripheral blood or BALF gamma/delta T cells relative to the total number of lymphocytes was similar in the four groups. Although the absolute number of gamma/delta T cells in BALF was significantly higher in DPB patients compared with the other three groups, the total lymphocyte number in BALF in DPB patients was increased and the number of BALF gamma/delta T cells correlated with the total lymphocyte number in BALF. Furthermore, the percentage and number of BALF gamma/delta T cells were not related to a certain group of pathogenic organisms or the number of colony-forming units. Our results suggest that gamma/delta T cells are unlikely to play a part in chronic lower respiratory tract infection.

Adult↗
PubMed1997

Elevated levels of soluble adhesion molecules in serum of patients with diffuse panbronchiolitis.

STUDY OBJECTIVE: Adhesion molecules have been implicated in the pathogenesis of inflammatory diseases. This study was designed to determine whether soluble adhesion molecules in serum reflect the disease activity in diffuse panbronchiolitis (DPB). PATIENTS AND METHODS: Using an enzyme-linked immunosorbent assay, we measured the serum levels of soluble L-, E-, and P-selectin (sL-, sE-, and sP-selectin), intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 in 27 patients with DPB, 13 with bronchiectasis, and 15 normal adults. BAL was also performed, and the levels of interleukin (IL)-8 and IL-1 beta in BAL fluid (BALF) were measured. RESULTS: The serum levels of these molecules were significantly elevated in DPB patients compared with the control subjects. DPB patients also had significant high levels of circulating sE- and sP-selectin compared with patients with bronchiectasis. There was a significant correlation between serum sE-selectin and the percentage of neutrophils in BALF in all patients. There was a significant inverse correlation between serum sE-selectin and percent vital capacity in DPB patients. In the same patients, the relationships between serum sE-selectin and BALF concentrations of IL-1 beta as well as between serum sL-selectin and BALF IL-8 were also significant. Treatment of DPB patients with macrolides significantly reduced the serum levels of these soluble adhesion molecules and BALF concentrations of IL-1 beta and IL-8. CONCLUSIONS: Our results suggest that these soluble adhesion molecules, particularly selectins, may reflect the disease activity of DPB, and that their levels may be regulated by cytokines produced in the lungs.

Adult↗
PubMed1997

Involvement of IL-4 in human glomerulonephritis: an in situ hybridization study of IL-4 mRNA and IL-4 receptor mRNA.

Interleukin-4 (IL-4) has been recently implicated in the pathogenesis of glomerulonephritis. However, the expression of IL-4 and IL-4 receptor (IL-4R) in human kidney has not been fully determined. Nonradioactive in situ hybridization was used to examine the expression of IL-4 mRNA and IL-4R mRNA in tissues from normal kidneys and specimens from a variety of human kidney diseases. In normal glomeruli, a few mesangial cells and cells of the Bowman's capsule weakly expressed IL-4 and IL-4R mRNA, whereas in diseased glomeruli both mRNA types were strongly expressed in resident glomerular cells, including mesangial cells, glomerular epithelial cells, and cells of the Bowman's capsule. The relationship between the expression of these mRNA and the degree of glomerular injury was different in different types of glomerulonephritis. In IgA nephropathy and non-IgA mesangial proliferative glomerulonephritis, IL-4 expression correlated positively with the degree of mesangial hypercellularity and extracellular matrix expansion. However, IL-4R expression was relatively constant. In contrast, the expression of IL-4 and IL-4R mRNA correlated negatively with the degree of glomerular injury in lupus nephritis. Coexpression and discordant expression of these mRNA forms were observed in individual cells. In tubulointerstitium with severe lesions, IL-4 mRNA and IL-4R mRNA were observed in atrophic tubules and some of the infiltrating cells and fibroblasts. The interstitial expression of these mRNA forms was similar in IgA nephropathy, non-IGA mesangial proliferative glomerulonephritis, and lupus nephritis and correlated positively with the degree of tubulo-interstitial changes. These results suggest that an autocrine and/or paracrine pathway of IL-4 is present in human diseased kidneys and that IL-4 may be involved in tissue injury in glomerulonephritis.

Adult↗
PubMed1997

Massive adrenal hemorrhage secondary to metastasis of lung cancer.

Hemorrhagic adrenal metastasis from lung cancer is extremely rare, although adrenal involvement is common in widely disseminated cancer. We report a case of massive adrenal hemorrhage secondary to metastasis of lung cancer. A 47-year-old female was treated by left upper lobectomy and mediastinal lymph node resection for an adenocarcinoma with intrapulmonary metastasis in the left upper lobe. Eight months later, she presented with right flank and back pain, and abdominal ultrasonography and computed tomography showed a right solitary adrenal tumor with massive hemorrhage. The tumor was not resectable and partially responded to chemotherapy. A massive adrenal hemorrhage, secondary to metastasis of lung cancer, presents with nonspecific clinical signs and symptoms. In lung cancer patients with an acute flank or back pain, hemorrhagic adrenal metastasis should be considered in the differential diagnosis.

Acute Disease↗
PubMed1997

Bronchial artery aneurysm as a cause of atelectasis.

A 54-year-old nonsmoker female developed atelectasis of the anterior basal segment of the right lower lobe. A non-pulsating endobronchial tumor was observed bronchoscopically obstructing the right basal bronchus. The tumor was confirmed on arteriography to be a saccular aneurysm of the right bronchial artery. The aneurysm was treated with bronchial artery embolization. Bronchial artery aneurysm, without a predisposing disease, is quite rare, but should be considered as an etiological factor of atelectasis.

Aneurysm↗
PubMed1997

Aspirin-induced asthma as a risk factor for asthma mortality.

We have recently reported severe airway obstruction and bronchial hyperresponsiveness (BHR) in fatal asthma compared with patients without a history of near-fatal asthma. Based on these findings, we evaluated whether aspirin-induced asthma (AIA) is a risk factor for asthma mortality by analyzing pulmonary function and BHR. FEV1.0% and methacholine inhalation threshold were significantly lower in the fatal asthma group compared with the AIA and non-AIA groups. However, there were no significant differences between the AIA and non-AIA groups. Our results suggested that AIA is not a risk factor for asthma mortality if avoidance of aspirin and aspirin-like drugs is assured.

Adult↗
PubMed1997

Evaluation of plasma (1-->3)-beta-D-glucan measurement by the kinetic turbidimetric Limulus test, for the clinical diagnosis of mycotic infections.

The present multicentre clinical study was conducted to assess the clinical utility of a new diagnostic method for deep mycosis in which (1-->3)-beta-D-glucan, a fungal cell wall component existing in plasma, was quantitatively measured by the kinetic turbidimetric Limulus test (WB003). Plasma (1-->3)-beta-D-glucan concentrations were 0.57 +/- 0.10 microgram/l in 92 healthy subjects and 0.62 +/- 0.32 microgram/l in 26 patients with non-mycotic diseases (disease control group). In comparison with these healthy subjects and patients with non-mycotic diseases, patients with mycosis had significantly higher plasma (1-->3)-beta-D-glucan concentrations: 19.63 +/- 73.28 micrograms/l in 12 patients with candidaemia, 11.28 +/- 21.42 micrograms/l in 7 patients with urinary Candida infection, 4.84 +/- 12.71 micrograms/l in 5 patients with pulmonary candidiasis, and 12.21 +/- 31.31 micrograms/l in 4 patients with invasive pulmonary aspergillosis. On the statistical analysis of these data, a cut-off value was set at 1.0 microgram/l. Using this cut-off value, 3 patients with pulmonary cryptococcosis and 4 patients (4/6) with pulmonary aspergilloma were all negative with low plasma (1-->3-beta-D-glucan levels. The test WB003 provided equivalent or higher efficiency of diagnosis of candidiasis and aspergillosis, in comparison with commercially available antigen detection kits, demonstrating its utility as a diagnostic reagent. It may also be useful in assessing therapeutic effectiveness when used periodically after treatment.

Adolescent↗
PubMed1997

Intraglomerular C3 synthesis in rats with passive Heymann nephritis.

Passive Heymann nephritis (PHN), a model of human membranous nephropathy, is an immune-complex-mediated glomerulonephritis characterized by the presence of complement-dependent tissue injury. Recent studies have confirmed the synthesis of C3, involved in both the classical and alternative pathways of complement, in injured human and animal renal tissues. However, there is little clear information on the role of local C3 synthesis in the pathogenesis of nephritides such as PHN. In the present study, using nonradioactive in situ hybridization and semiquantitative reverse transcriptase polymerase chain reaction, we examined C3 synthesis in the kidney and its contribution to tissue injury in a rat model of PHN induced by the injection of polyclonal anti-gp330 antibody. C3 mRNA was localized in mesangial cells, glomerular epithelial cells, and cells of Bowman's capsule. During the early stages of PHN, C3 mRNA expression was detected in mesangial cells and glomerular epithelial cells, whereas such expression was limited to mesangial cells during the late stages of the disease. Focal, weak C3 mRNA expression was detected in tubular epithelial cells and occasionally in the interstitium. Semiquantitative polymerase chain reaction demonstrated that the level of C3 mRNA expression correlated with that of proteinuria. Our results suggest that renal cells synthesize C3 mRNA in PHN in a site-specific manner and that locally produced C3 is associated with the development of proteinuria in this model.

Animals↗