Biomedical subjects

Minoru Hasegawa

Publications and source records attributed to Minoru Hasegawa.

61 records · Page 4Linked to original sources

PubMed2002

The cutaneous reverse Arthus reaction requires intercellular adhesion molecule 1 and L-selectin expression.

The deposition of immune complexes (IC) induces an acute inflammatory response with tissue injury. IC-induced inflammation is mediated by inflammatory cell infiltration, a process highly regulated by expression of multiple adhesion molecules. To assess the role of L-selectin and ICAM-1 in this pathogenetic process, the cutaneous reverse passive Arthus reaction was examined in mice lacking L-selectin (L-selectin(-/-)), ICAM-1 (ICAM-1(-/-)), or both (L-selectin/ICAM-1(-/-)). Edema and hemorrhage, which peaked 4 and 8 h after IC challenge, respectively, were significantly reduced in L-selectin(-/-), ICAM-1(-/-), and L-selectin/ICAM-1(-/-) mice compared with wild-type littermates. In general, edema and hemorrhage were more significantly inhibited in ICAM-1(-/-) mice than in L-selectin(-/-) mice, but were most significantly reduced in L-selectin/ICAM-1(-/-) mice compared with ICAM-1(-/-) or L-selectin(-/-) mice. Decreased edema and hemorrhage correlated with reduced neutrophil and mast cell infiltration in all adhesion molecule-deficient mice, but leukocyte infiltration was most affected in L-selectin/ICAM-1(-/-) mice. Reduced neutrophil and mast cell infiltration was also observed for all mutant mice in the peritoneal Arthus reaction. Furthermore, cutaneous TNF-alpha production was inhibited in each deficient mouse, which paralleled the reductions in cutaneous inflammation. These results indicate that ICAM-1 and L-selectin cooperatively contribute to the cutaneous Arthus reaction by regulating neutrophil and mast cell recruitment and suggest that ICAM-1 and L-selectin are therapeutic targets for human IC-mediated disease.

Animals↗

PubMed2002

Intercellular adhesion molecule-1 and L-selectin regulate bleomycin-induced lung fibrosis.

The development of bleomycin-induced lung injury, a model of pulmonary fibrosis, results from inflammatory cell infiltration, a process highly regulated by the expression of multiple adhesion molecules. At present, the identity and role of the adhesion molecules involved in the fibrotic process are unknown. Therefore, bleomycin-induced pulmonary fibrosis was examined in mice lacking L-selectin (L-selectin(-/-)) expression, intercellular adhesion molecule-1 (ICAM-1) expression, or both. After 16 days of intratracheal bleomycin challenge, collagen deposition was inhibited in both L-selectin(-/-) and ICAM-1(-/-) mice when compared with wild-type littermates. Interestingly, collagen deposition was virtually eliminated in L-selectin/ICAM-1(-/-) mice relative to either the L-selectin(-/-) or ICAM-1(-/-) mice. Decreased pulmonary fibrosis was associated with reduced accumulation of leukocytes, including neutrophils and lymphocytes. Decreased mRNA expression of proinflammatory cytokines and transforming growth factor (TGF)-beta1 paralleled the inhibition of collagen deposition. The present study indicates that L-selectin and ICAM-1 play a critical role in pulmonary fibrosis by mediating the accumulation of leukocytes, which regulate the production of proinflammatory cytokines and TGF-beta1. This suggests that these adhesion molecules are potential therapeutic targets for inhibiting human pulmonary fibrosis.

Animals↗

PubMed2002

Discrimination of subtypes of small adenocarcinoma in the lung with thin-section CT.

We studied the usefulness of thin-section CT in discriminating two categories of adenocarcinoma in the lung. Thin-section CT findings, such as, lesion size, ground-glass opacity (GGO) areas of lesion and presence or absence of lobulation, coarse spiculation, air bronchogram, small air space, or pleural tag of lesion in 62 consecutive patients with 62 adenocarcinomas (35 type A or B tumors (Noguchi's classification) and 27 type C tumors) of < or =20 mm, including 36 women and 26 men with a mean age of 64 years were analyzed. We performed stepwise logistic modeling using all the CT findings as independent variables to estimate the significant factors for discriminating type C from type A or B tumor. Lesion size in type C tumors was significantly (P<0.001) greater than that in type A or B tumors. GGO areas in type C tumors were significantly (P<0.001) smaller than that in type A or B tumors. The prevalence of coarse spiculation, air bronchogram, and pleural tag in type C tumors was significantly greater (P=0.001, 0.010, and <0.001, respectively) than that in type A or B tumors. Logistic modeling revealed that the GGO area was the only significant factor for discriminating two categories (P<0.001). Using the percentage of GGO areas for predicting type C tumor, 40% or less showed the highest accuracy of 85% with 70% sensitivity and 97% specificity. GGO areas of 30% or less had no false-positive diagnosis (100% specificity) with 81% accuracy but its sensitivity was low (56%). Thin-section CT was useful in discriminating two categories of adenocarcinoma in the lung.

Adenocarcinoma↗

PubMed2002

Prognostic significance of high-resolution CT findings in small peripheral adenocarcinoma of the lung: a retrospective study on 64 patients.

OBJECTIVE: We studied the prognostic importance of high-resolution CT (HRCT) findings in lung adenocarcinomas. PATIENTS AND METHODS: HRCT findings (lesion size, percentage of ground-glass opacity (GGO) areas of lesion, and presence or absence of lobulation, coarse spiculation, air space, pleural tag, and multiplicity of lesion), clinical data (age and surgical method), and pathologic findings (tumor subtypes and presence or absence of nodal metastasis) in 64 consecutive patients with 64 peripheral adenocarcinomas of 20 mm or less (mean, 13 mm), including 36 women and 28 men with a mean age of 64 years were analyzed and correlated with survival of the patients using Kaplan-Meier method and stepwise Cox proportional hazards modeling. Follow-up periods of the patients ranged from 6 to 45 months (mean, 22 months). Tumors were classified into six subtypes (types A-F) according to tumor growth patterns defined by Noguchi et al. RESULTS: Six (9%) of the 64 patients died of lung cancer. In univariate analyses, a significant difference was noted for lesion size (P=0.043), the percentage of GGO areas (P=0.005), and tumor subtypes (P=0.006). Lesion size of <15 mm (n=35), a lesion with GGO areas of >57% (n=36), and type A (n=16) or type B adenocarcinomas (n=16) indicated a significantly better survival. In multivariate analyses using these three parameters as independent variables, the percentage of GGO areas was the only significant independent factor for survival (P=0.044, relative risk=0.95). CONCLUSION: GGO areas measured on HRCT may have an independent prognostic significance of small adenocarcinomas of the lung.

Adenocarcinoma↗

PubMed2002

Complement receptors CD21/35 link innate and protective immunity during Streptococcus pneumoniae infection by regulating IgG3 antibody responses.

The CD21/35 receptor provides an important link between innate and adaptive immunity. Its importance during protective immune responses to encapsulated extracellular bacteria was assessed using a new line of mice completely deficient in CD21/35 expression (CD21/35(-/-)). CD21/35 expression was essential for the rapid trapping of C3dg-antigen complexes by B cells in vivo, especially in splenic marginal zones. Despite normal B cell development in CD21/35(-/-) mice, T cell-independent and -dependent antibody responses to low-dose antigens were significantly decreased, with a striking impairment in IgG3 responses. Accordingly, CD21/35(-/-) mice were more susceptible to acute lethal Streptococcus pneumoniae infection. Thus, CD21/35 expression is critical for early protective antibody responses to lethal pathogens that rapidly multiply and quickly overwhelm the immune system.

Animals↗

PubMed2002

CD19-dependent B lymphocyte signaling thresholds influence skin fibrosis and autoimmunity in the tight-skin mouse.

The tight-skin (TSK/+) mouse, a genetic model for human systemic sclerosis (SSc), develops cutaneous fibrosis and autoantibodies against SSc-specific target autoantigens. Although molecular mechanisms explaining the development of fibrosis and autoimmunity in SSc patients or TSK/+ mice remain unknown, we recently demonstrated that SSc patients overexpress CD19, an important regulatory molecule expressed by B lymphocytes. B cells from CD19-deficient mice are hyporesponsive to transmembrane signals, while B cells overexpressing CD19 are hyperresponsive and generate autoantibodies. In this study, TSK/+ B cells also exhibited a hyperresponsive phenotype with decreased surface IgM expression, enhanced serum Ig production, and spontaneous autoantibody production. Moreover, CD19 tyrosine phosphorylation was constitutively augmented in TSK/+ B cells. CD19-mediated [Ca(2+)](i) responses, Vav phosphorylation, and Lyn kinase activity were similarly enhanced. Studies of TSK/+ mice deficient in CD19 expression demonstrated that CD19 deficiency significantly decreased skin fibrosis in TSK/+ mice. Additionally, CD19 loss in TSK/+ mice upregulated surface IgM expression and completely abrogated hyper-gamma-globulinemia and autoantibody production. CD19 deficiency also inhibited IL-6 production by TSK/+ B cells. Thus, chronic B cell activation resulting from augmented CD19 signaling in TSK/+ mice leads to skin sclerosis possibly through IL-6 overproduction as well as autoimmunity.

ADP-ribosyl Cyclase↗

PubMedDate not supplied

High-resolution CT features: prognostic significance in peripheral lung adenocarcinoma with bronchioloalveolar carcinoma components.

BACKGROUND: Based on Noguchi's classification, adenocarcinomas with bronchioloalveolar carcinoma (BAC) components have a heterogeneous prognosis. However, until now, the prognostic factors in this tumor category have not been clarified. OBJECTIVES: We studied the prognostic significance of high-resolution CT (HRCT) findings in this tumor subtype. MATERIALS AND METHODS: HRCT findings [lesion size, percentage of ground-glass opacity (GGO) areas in the lesion, presence or absence of lobulation, coarse spiculation, pleural tag, satellite lesion, air bronchogram, and site of the lesion], clinical data (age, gender and surgical method), and pathologic findings (degree of tumor differentiation and presence or absence of nodal metastasis) were analyzed in 52 consecutive patients with adenocarcinoma with BAC components <3 cm (mean, 1.7 cm). The patients included 32 women and 20 men with a mean age of 66 years. The results correlated with survival using univariate and multivariate analysis. The mean follow-up period was 41 months. RESULTS: Nine (17%) of the 52 patients died of lung cancer. In univariate analysis, a significant difference was found for lobulation (p = 0.018), %GGO (p = 0.043), air bronchogram (p = 0.003), site of lesion (p = 0.034), degree of tumor differentiation (p = 0.001), and nodal metastasis (p = 0.040). Multivariate analysis using the 6 factors that were significant in univariate analysis as independent variables revealed that an air bronchogram (p = 0.010) and the degree of tumor differentiation (p = 0.008) were significant independent factors for survival. CONCLUSION: The presence of an air bronchogram on HRCT may have an independent prognostic significance in lung adenocarcinoma with BAC components.

Adenocarcinoma, Bronchiolo-Alveolar↗