Soluble intercellular adhesion molecule-1 (ICAM-1) in sera and bronchoalveolar lavage (BAL) fluids of extrinsic allergic alveolitis.

ICAM-1 plays an important role in inflammatory diseases. We analysed ICAM-1 expression on BAL fluid cells and measured soluble ICAM-1 (sICAM-1) concentrations in sera and BAL fluids from patients with extrinsic allergic alveolitis (EAA). We found significantly increased cellular ICAM-1 expression on BAL fluid lymphocytes and alveolar macrophages, and significantly increased values of circulating and BAL fluid sICAM-1 in EAA patients compared with controls. Successive measurement showed prompt decrease of both sICAM-1 values in EAA patients during periods when antigen exposure was prevented. In BAL fluids from EAA patients, sICAM-1 values significantly correlated to neutrophil and ICAM-1+ lymphocyte counts. In EAA patients, circulating and BAL fluid sICAM-1 values has significant negative correlations to values of carbon monoxide diffusing capacity and to time intervals between last episode and sample collection. However, these values had significant positive correlation to values of alveolar-arterial oxygen pressure difference. In EAA, antigen exposure appears to induce cellular ICAM-1 expression on BAL fluid cells, and also appears to up-regulate shedding of ICAM-1 in the alveolar lining fluid and in the circulation. The sICAM values appear to reflect disease activity of EAA.     

Increased circulating interleukin-12 (IL-12) p40 in pulmonary sarcoidosis

In sarcoidosis, a T helper 1 (Th1) response is an essential event and the up-regulation of interleukin-12 (IL-12) has been detected in affected disease sites. In order to investigate the clinical usefulness of circulating IL-12, we measured the serum concentrations of IL-12 by ELISA and performed immunohistochemistry using specific MoAbs for IL-12 in the lungs and scalene lymph nodes of patients with sarcoidosis. The serum concentration of IL-12 p40 was detectable in all 45 patients with pulmonary sarcoidosis and 18 normal controls, whereas that of IL-12 p70 was undetectable. The serum concentrations of IL-12 p40 in pulmonary sarcoidosis were significantly higher than those of the normal controls, especially in cases with abnormal intrathoracic findings detected by chest roentogenogram. The serum concentrations of interferon-gamma (IFN-gamma) also increased compared with those of normal controls and there was a significant positive correlation between the serum concentrations of IL-12 p40 and IFN-gamma. Furthermore, serum angiotensin-converting enzyme (ACE) and lysozyme, which are known to be useful markers for disease activity in sarcoidosis, correlated well with the serum concentrations of IL-12 p40. The positive 67Ga scan group (for lung field) had significantly elevated serum IL-12 p40 levels compared with those of the negative group. No bioactivity of IL-12 p70 was detected in three sarcoid cases sera by using the IL-12 responsive cell line. Finally, the immunohistochemical approach revealed that IL-12 p40 was expressed in the epithelioid cells and macrophages of sarcoid lungs and lymph nodes. We concluded that the production of IL-12 p40 was far greater in the sera and we have demonstrated this to be a useful clinical marker for disease activity and the Th1 response in pulmonary sarcoidosis.     

Immunolocalization of extracellular matrix proteins and integrins in sarcoid lymph nodes

 To improve our understanding of the role of extracellular matrix (ECM) proteins and integrins during the processes of granuloma formation in sarcoidosis, we examined the distribution of ECM proteins and the expression of integrins in sarcoid lymph nodes by immunohistochemical methods. We also examined the expression of transforming growth factor-β1 (TGF-β1), which is one of major regulators for synthesis of ECM proteins. Most ECM proteins were detected in the periphery of the granulomas in a concentric pattern, and fibronectin was diffusely detected from an early to a regressive stage. Compared with normal lymph nodes, most β1-integrin subfamilies (α1, α4, α5 and α6) were more strongly expressed on lymphocytes around the granulomas. Epithelioid cells exhibited strong expression of the α5 molecule. Fibroblasts exhibited the expression of the α2 and α5 molecules surrounding ECM proteins. The α5β1 molecule had a distribution similar to that of fibronectin. TGF-β1 was detected in epithelioid cells throughout the various evolutional stages and its expression was especially marked in mature granulomas. Interaction of fibronectin and the α5β1 molecule may have an important role in the process of formation of sarcoid granuloma. The expression of TGF-β1 may be involved in the regression of sarcoid granuloma by initiating fibrosis and atrophy of epithelioid cells. Received: 2 December 1997 / Accepted: 19 February 1998     

Pneumocystis carinii carriage in immunocompromised patients with and without human immunodeficiency virus infection

Eighty-one bronchoalveolar lavage (BAL) specimens obtained from 26 HIV-infected, 45 non-HIV immunosuppressed and 10 immunocompetent patients with primary pulmonary diseases were analysed for the presence of Pneumocystis carinii by staining and by P. carinii 5S rDNA determined by PCR. P. carinii was observed by staining of BAL specimens from HIV-infected patients significantly more frequently than those from immunocompromised hosts without HIV infection (57.7% versus 20.0%, respectively). P. carinii 5S rDNA was detected by PCR assay in seven (26.9%) HIV-infected individuals, which was significantly more frequent than for four (8.9%) immunosuppressed patients without HIV infection, for whom staining was negative. None of these patients developed P. carinii pneumonia (PCP) within the follow-up period. BAL specimens from 10 immunocompetent patients with pulmonary disorders were negative for PCP by both staining and PCR assay.     

Phenotypic analysis in peripheral blood lymphocytes of patients with pulmonary tuberculosis]

In order to clarify the immunological aspects of tuberculosis, phenotype of peripheral blood lymphocytes was analyzed in 96 patients with pulmonary tuberculosis and 43 normal controls. In tuberculosis, CD8 positive T cells were significantly decreased in comparison with normal controls and regarding expression of CD3, CD4, CD19, CD16 and gamma delta T cell receptor (TCR), there was no significant difference between tuberculosis and normal controls, though in tuberculosis CD4 positive T cells tended to be high as compared to normal controls. With respect to previous therapeutic condition, the group with previous chemotherapy had significantly high CD4 positive cells, low CD8 positive cells and low gamma delta TCR positive cells as compared to the group without previous chemotherapy. Between groups divided by Type or Expansion of pulmonary tuberculosis without previous chemotherapy, there was no significant difference regarding any surface markers. Regarding pulmonary tuberculosis with previous chemotherapy, the group of Type II had significantly high CD4 positive cells and low CD8 positive cells as compared to Type III, and in the group of Expansion 3, CD19 positive cells were significantly high as compared to Expansion 2. Characteristic of phenotype in peripheral blood lymphocytes of patients with pulmonary tuberculosis is predominant CD4 positive cells in a corresponding decrease in the proportion of CD8 positive cells and is no elevation of gamma delta TCR positive T cells.     

Increased levels of interleukin-18 in patients with pulmonary sarcoidosis

Interleukin-18 (IL-18) has recently been identified as an interferon-gamma (IFN-gamma)-inducing factor, and it plays an important role in T helper 1 (Th1) response. We measured the serum levels of IL-18 and IFN- gamma in 37 patients with pulmonary sarcoidosis and 25 healthy control subjects. We also measured the levels of IL-18 and IFN-gamma in 10-fold concentrated bronchoalveolar lavage (BAL) fluids of 19 patients with pulmonary sarcoidosis and 9 healthy control subjects (all lifelong nonsmokers). The levels of serum IL-18 and IFN-gamma were significantly increased in patients with sarcoidosis. The levels of BAL fluid IL-18 were significantly elevated in patients with sarcoidosis, however, the IFN-gamma levels of the patients and control subjects were all below sensitivity. Serum IL-18 levels significantly correlated with serum IFN-gamma levels and lysozyme activity. The patients positive for gallium-67 ((67)Ga) scan had significantly elevated serum IL-18 levels as compared with those of the negative patients. BAL fluid IL-18 levels significantly correlated with serum IL-18 levels in patients with sarcoidosis, and there was a significant correlation between IL-18 levels and lymphocyte proportions in sarcoid BAL fluids. In patients with sarcoidosis, IL-18 seems to induce IFN-gamma production and IL-18 levels in sera may reflect disease activity of sarcoidosis.     

Thymidine phosphorylase and vascular endothelial growth factor in patients with Stage I lung adenocarcinoma

BACKGROUND: Thymidine phosphorylase (TP) has chemotactic activity in endothelial cells in vitro and angiogenic activity in vivo. However, the clinical significance of TP and cooperative roles of TP with other angiogenic factors have remained unclear in nonsmall cell lung carcinoma (NSCLC). METHODS: The authors stained for TP, vascular endothelial growth factor (VEGF), and basic fibroblast growth factor (bFGF) in 132 tumors from patients with Stage I NSCLC. They compared TP, VEGF, and bFGF expression levels with microvessel counts (MVCs), macrophage counts, mast cell counts, and clinical outcomes of patients with Stage I NSCLC. RESULTS: In adenocarcinoma samples, only stromal cell-TP expression and tumor cell-VEGF expression were associated with MVCs and mast cell counts but not with macrophage counts. In squamous cell carcinoma samples, there were no significant associations of the expression of any examined angiogenic factors with MVCs, mast cell counts, or macrophage counts. More importantly, only among patients with Stage I adenocarcinoma of the lung did patients in the stromal cell-TP positive tumor group and in the tumor cell-VEGF positive tumor group have a significantly worse prognosis compared with patients in the stromal cell-TP negative tumor group and in the tumor cell VEGF negative group, respectively. In addition, among patients with Stage I adenocarcinoma, patients in the stromal cell-TP positive and tumor cell-VEGF positive tumor group had a significantly worse prognosis among the four groups. CONCLUSIONS: TP induction in tumoral stroma, but not in tumor cells, and tumor cell-VEGF induction may promote angiogenesis cooperatively in adenocarcinoma of the lung. Stromal cell-TP expression and tumor cell-VEGF expression may be important prognostic factors in adenocarcinoma of the lung, and stromal cell-TP expression may be a marker of active remodeling stroma in adenocarcinoma of the lung.     

A case of nonspecific interstitial pneumonia associated with amyopathic dermatomyositis efficiently treated with a combination of cyclosporin A and prednisolone]

A 36-year-old man was admitted to our hospital complaining of cough, dyspnea on exertion, skin eruptions, and joint pain. Characteristic skin lesions such as erythema around the nails, telangiectasis, and edema of the eyelids were observed in this patient. He had never complained of muscle symptoms, and his laboratory examinations showed no elevation of either CPK or aldolase. From several lines of evidence including the skin biopsy findings, amyopathic dermatomyositis was diagnosed. Chest X-ray films showed subpleural funicular opacities and consolidation in both lower lung fields. Lung biopsy specimens taken under video-assisted thoracoscopic surgery revealed nonspecific interstitial pneumonia, group II. Oral prednisolone treatment was initiated at 60 mg daily together with oral cyclosporin A (100-150 mg daily). The minimum serum concentration of cyclosporin A was maintained between 100 and 200 ng/ml. Respiratory symptoms gradually improved, and the oral prednisolone dose was tapered off. Pulmonary function and chest CT findings showed marked improvement.     

Self-reported rate of eating is significantly associated with body mass index in Japanese patients with type 2 diabetes. Japan Diabetes Clinical Data Management Study Group (JDDM26)

We examined whether the rate of eating was associated with the body mass index and glycemic control status in Japanese patients with type 2 diabetes (50% women, mean±SD age 59.4±7.5years). Rapid eating was significantly associated with body mass index (p=0.047). The body mass index of those who reported eating quickly was 0.8kg/m(2) higher than in individuals who reported eating at medium speed even after adjustment for known confounders. No significant association was observed between the rate of eating and HbA(1c). Our findings suggest an association between self-reported rapid eating and an elevated body mass index in patients with type 2 diabetes.