Ikuma Kasuga

Tumor-related leukocytosis is linked with poor prognosis in patients with lung carcinoma.

Tumor‐related leukocytosis is a paraneoplastic syndrome that is encountered occasionally in the clinical course of patients with lung carcinoma. Recently, autonomous production of hematopoietic cytokines (granulocyte‐colony stimulating factor [G‐CSF], granulocyte‐macrophage–colony stimulating factor [GM‐CSF], and interleukin‐6 [IL‐6]) were identified in some of these patients. However, the incidence and clinical characterization of this phenomenon have not been clarified.

Sarcoidosis induced by interferon therapy for chronic myelogenous leukaemia

A 31‐year‐old male was diagnosed as having chronic myelogenous leukaemia and has been treated with hydroxyurea and interferon‐α since February 1995. After 16 months, he complained of low‐grade fever and a cough. Bilateral hilar lymph node enlargement was detected on the chest X‐ray film and multiple subcutaneous erythematous nodules appeared. A skin biopsy revealed subcutaneous sarcoid granuloma. Two months after the cessation of interferon therapy, the subcutaneous nodules and the hilar lymph node enlargement resolved. It is possible that continuous interferon administration can promote granuloma formation in sarcoidosis by activating T cells and macrophages.

Detection of nocturnal wheezing in bronchial asthma using intermittent sleep tracheal sounds recording

Common clinical features of bronchial asthma include bronchoconstriction during the night, particularly while asleep. Although bronchoconstriction reduces the quality of life and can cause life‐threatening events, a clinical technique for evaluating bronchoconstriction during sleep has not been widely applied. In this study, we measured nocturnal wheezing by intermittent sleep tracheal sounds recording (ISTSR) to detect bronchoconstriction during the hours of sleep. Using ISTSR, we studied the number and duration of nocturnal wheezing episodes in 27 adult patients with bronchial asthma. Nocturnal wheezing was detected in 36 of 39 recordings. Although the pattern of hourly nocturnal wheezing count (hourly NWC pattern) varied among subjects, there appeared to be a reproducible pattern within individuals. When wheezing alternated between long and short duration, bronchoconstriction tended to be more severe. The NWC in 1 h (NWC/H) was positively correlated with subjective symptoms and inversely correlated with the morning per cent peak expiratory flow. The hourly NWC was significantly greater at 05:00 than that at midnight. Intermittent sleep tracheal sounds recording has potential to be a non‐invasive clinical tool for detecting nocturnal bronchoconstriction during hours of sleep in patients with asthma.

Clinical evaluation of serum type IV collagen 7S in idiopathic pulmonary fibrosis

Abstract Type IV collagen is one of the major components of the basement membrane (BM). 7S domain (7S collagen) of type IV collagen is an N‐terminal peptide which is stable against protease and heat. We investigated serum concentration of 7S collagen in patients with idiopathic pulmonary fibrosis (IPF) and other pulmonary diseases. The aim of this study was to evaluate whether changes in the serum concentration of 7S collagen reflect the fibrotic process of IPF. We measured the concentration of serum 7S collagen with radioimmunoassay in patients with IPF, chronic pulmonary emphysema (CPE), sarcoidosis, infectious pulmonary diseases (IPD) and normal healthy controls. We also monitored 7S collagen during the clinical course in some patients with IPF and investigated the correlation between the serum 7S collagen, and lactate dehydrogenase (LDH) and erthrocyte sedimentation rate (ESR) in patients with IPF. Patients with IPF showed significantly higher serum concentration of 7S collagen than other pulmonary diseases and healthy controls. The serum concentration of 7S collagen significantly decreased in IPF patients who showed roentgenographic improvement after corticosteroid treatment. There was a correlation between the serum 7S collagen and LDH, and ESR. In conclusion, serum concentrations of 7S collagen increase in patients with IPE The measurement of 7S collagen is useful for the evaluation of fibrotic change in the lung.

Protein kinase inhibitor attenuates an increase in endothelial monolayer permeability induced by tumour necrosis factor-α

Abstract We questioned the mechanism of the increase in pulmonary endothelial permeability induced by tumour necrosis factor‐α (TNF‐α), a cytokine implicated in the pathogenesis of adult respiratory distress syndrome. As a measure of permeability, we determined the albumin transferred across cultured pulmonary endothelial monolayers prepared on a porous filter. The agents evaluated included protein kinase inhibitors H‐7 and H‐8, a calmodulin antagonist W‐7, and protein kinase C (PKC) activators, phorbol myristate acetate (PMA) and SC‐9. H‐7, more potent in inhibiting PKC than H‐8, failed to attenuate the increase in permeability induced by TNF‐α. Neither PMA nor SC‐9 increased permeability. However, H‐8, which is a potent inhibitor of cyclic nucleotide‐dependent protein kinases, prevented the increase in permeability induced by TNF‐α. These results suggest that protein kinases other than PKC are involved in the signal transduction in endothelial permeability increase induced by TNF‐α. Calmodulin pathway may not be implicated in the increase in permeability induced by TNF‐α.

Direct Demonstration of the Productive Capability of Cytokines at the Single Cell Level in Lung Sarcoidosis Using Multicolor Cytometry

Background: Sarcoidosis is a chronic systemic disorder of unknown etiology characterized by noncaseating epithelioid cell granulomatous lesions, around which an increasing number of CD4+ T cells infiltrate. These CD4+ T cells may release interferon-γ (IFN-γ) and interleukin-2 (IL-2). These cytokines are considered to play an important role in pathogenesis of sarcoidosis. Methods: We employed a modification of Jung’s method using multicolor flow cytometry to assess the capability of single cells obtained from bronchoalveolar lavage (BAL) fluid to produce various cytokines. BAL CD4+ T cell production of IFN-γ, IL-2 and IL-4 after phorbol ester and ionomycin stimulation were studied. Results: The percentage of IFN-γ- and IL-2-producing CD4+ T cells was significantly higher in patients with sarcoidosis compared to healthy volunteers [84.7 ± 7.5 vs. 51.2 ± 14.8% (p < 0.005), and 75.3 ± 8.7 vs. 39.8 ±11.0% (p < 0.001), respectively]. No significant difference in the percentage of IL-4-producing CD4+ T cells was noted (1.2 ± 0.6 vs. 3.5 ± 2.6%; not significant), whereas the absolute number of IL-4-producing CD4+ T cells was significantly higher in patients with sarcoidosis compared to healthy volunteers (563.6 ± 330.2 vs. 50.9 ± 66.9/ml; p < 0.005). In the IL-4-producing CD4+ T cells, about 80% of cells concomitantly produced IFN-γ and more than 60% of cells also produced IL-2. Conclusion: We demonstrate that Th1-like-producing cells are predominant in the CD4+ as well as in the CD8+ T cell subset of patients with sarcoidosis. We for the first time demonstrated concomitant capabilities of BAL CD4+ T cells to produce Th1 and Th2 cytokines at the single cell level by multicolor flow cytometry.