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Biomedical subjects

K Shigehara

Publications and source records attributed to K Shigehara.

14 recordsLinked to original sources

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-beta1 (TGF-beta1), 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 beta1-integrin subfamilies (alpha1, alpha4, alpha5 and alpha6) were more strongly expressed on lymphocytes around the granulomas. Epithelioid cells exhibited strong expression of the alpha5 molecule. Fibroblasts exhibited the expression of the alpha2 and alpha5 molecules surrounding ECM proteins. The alpha5beta1 molecule had a distribution similar to that of fibronectin. TGF-beta1 was detected in epithelioid cells throughout the various evolutional stages and its expression was especially marked in mature granulomas. Interaction of fibronectin and the alpha5beta1 molecule may have an important role in the process of formation of sarcoid granuloma. The expression of TGF-beta1 may be involved in the regression of sarcoid granuloma by initiating fibrosis and atrophy of epithelioid cells.

Extracellular Matrix Proteins

Cranial defect and decrease in cerebral blood flow resulting from deep contact burn of the scalp in the neonatal period.

A case of cranial defect in the anterior fontanelle region is reported. The patient suffered a deep contact burn on the right parietofrontal region in the neonatal period. At age 3 years, a bone defect of 30 x 20 mm was observed in the right parietofrontal region, including the anterior fontanelle, and the pulsation of the brain was palpable. Moreover, scintigraphy of cerebral blood flow using SPECT with 99mTc-HMPAO demonstrated extensive decrease in blood flow in the right parietosquamosal region. Cranioplasty was performed at 3 years and 4 months using split ribs grafts and at age 5 years and 4 months using split-thickness calvarial bone grafts. After the cranioplasty, there was no bony defect and no region of reduced blood flow. The child is developing well.

Brain

Circulating soluble intercellular adhesion molecule-1 (sICAM-1) in patients with sarcoidosis.

sICAM-1 has been elevated in sera of specific inflammatory diseases, and circulating sICAM-1 concentrations reflect disease activity in these diseases. We measured circulating sICAM-1 concentrations and serum angiotensin-converting enzyme (SACE) activity in patients with sarcoidosis. Patients with sarcoidosis had significantly increased circulating sICAM-1 concentrations (62.8 +/- 33.5 U/ml) and SACE activity (23.7 +/- 7.4 U/l) compared with controls (circulating sICAM-1 50.9 +/- 12.1 U/ml, and SACE 13.5 +/- 3.8 U/l). Successive measurements showed that circulating sICAM-1 values changed in parallel with disease activity in sarcoidosis. In the progressive disease group (progressed or without change for 2 years or more), circulating sICAM-1 values (102.2 +/- 35.3 U/ml) at the time of diagnosis were significantly increased compared with those in the regressive disease group (disappeared or regressed within 2 years) 46.4 +/- 12.6 U/ml). However, there was no significant difference in SACE activity of the regressive and progressive disease groups. Fifteen patients with a high value of circulating sICAM-1 (> 75 U/ml, mean of controls + 2 s.d.) all had progressive disease, while only 15 of 44 patients with a high value of SACE had progressive disease. Circulating sICAM-1 will be a useful blood marker to predict outcome and to monitor disease activity in sarcoidosis.

Adolescent

Lactic dehydrogenase-immunoglobulin G kappa complex in a patient with idiopathic interstitial pneumonia.

A female patient with idiopathic interstitial pneumonia (IIP) was admitted again 40 months after the diagnosis due to progression of clinical findings and increased activity of serum lactic dehydrogenase (LDH). Analysis of LDH isoenzyme disclosed a broad band between LDH4 and LDH5. Gel filtration and immunoelectrophoresis showed that immunoglobulin (Ig) G (kappa type) bound the LDH. With prednisolone and azathioprine, her symptoms and radiological findings improved concomitant with a decrease in the serum LDH activity. The LDH-IgG kappa complex disappeared in the circulation 14 months after initiation of the therapy. We report circulating LDH-Ig complex in a patient with IIP, which may be related to the disease progression of IIP.

Antigen-Antibody Complex

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.

Adult

Circulating gamma delta-T-cell-receptor-positive lymphocytes in sarcoidosis.

We investigated phenotypic surface markers of peripheral blood lymphocytes including expression of gamma delta T cell receptor (TCR gamma delta) in 185 patients with sarcoidosis and 42 normal subjects. The proportion of TCR gamma delta+ lymphocytes in peripheral blood of patients with sarcoidosis (5.5 +/- 5.4%) was significantly higher than in normal subjects (3.6 +/- 2.2%; p < 0.05). A number of patients with sarcoidosis had prominently increased levels of circulating TCR gamma delta+ lymphocytes. Successive measurements of circulating TCR gamma delta+ lymphocytes demonstrated the persistence of increased levels of circulating TCR gamma delta+ lymphocytes. We divided the patients with sarcoidosis into two groups, one with high, the other with low TCR gamma delta+ expression. Compared with the low-value group, the high-value group had significantly decreased levels of circulating CD4+ lymphocytes, decreased incidence of a positive tuberculin reaction, and higher levels of serum angiotensin-converting enzyme and lysozyme, suggesting that these two groups may differ in their immunological response and disease activity of sarcoidosis. Measurement of TCR gamma delta+ expression in the circulation seems to be useful for estimating the disease activity of sarcoidosis.

Adolescent

Pulmonary cryptococcal infection in an untreated patient with sarcoidosis.

A 36-year-old housewife was referred to our hospital in March, 1993. Her chest X ray films showed mediastinal and bilateral hilar lymphadenopathy. She was confirmed to have pulmonary sarcoidosis. We did not administer any medications for her. Four months after the diagnosis of sarcoidosis, opacities with cavitation appeared on the chest X ray. Histologic findings of lung biopsy specimens revealed granulomas with the existence of encapsulated Cryptococci. We administered an antifungal drug, itraconazole. The opacities were greatly improved by the medication. We report focal pulmonary cryptococcal infection in an untreated patient with sarcoidosis.

Adult

Soluble intercellular adhesion molecule-1 (ICAM-1) in sera and bronchoalveolar lavage fluid of patients with idiopathic pulmonary fibrosis and pulmonary sarcoidosis.

ICAM-1 plays an important role in inflammatory diseases. To assess level of soluble ICAM-1 in the circulation and inflamed lesions, we measured levels of soluble ICAM-1 in the circulation and bronchoalveolar lavage fluid (BALF) of patients with idiopathic pulmonary fibrosis (IPF) and with pulmonary sarcoidosis (PS) and of healthy volunteers (HV), and we also analysed ICAM-1 expression of BALF cells in some patients and HV. IPF patients had significantly higher levels of circulating ICAM-1 than HV, while PS patients did not. By contrast, significantly increased levels of BALF soluble ICAM-1 were found in PS patients compared with those of HV, but not in IPF patients. There were no significant differences in the proportions of ICAM-1+ BALF lymphocytes in IPF patients, PS patients and HV, whereas significantly increased proportions of ICAM-1+ pulmonary alveolar macrophages were found in PS patients compared with those of HV, but not in IPF patients. There was a significant positive correlation of BALF soluble ICAM-1 levels to BALF lymphocyte proportions in PS patients. Although the source of BALF soluble ICAM-1 is unclear, BALF soluble ICAM-1 appears to reflect the grade of local activity of sarcoidosis. An interesting discrepancy between soluble ICAM-1 levels in the circulation and BALF was found in IPF patients, and this might be an important clue to an understanding of this disorder.

Adolescent

Increased level of circulating gamma/delta T cells in a patient with eosinophilic granuloma.

A patient with eosinophilic granuloma, histologically confirmed from open lung biopsy specimen, had a history of scarlet fever and a prominently high level of circulating gamma/delta T cells (25 percent) in comparison with normal levels (< 10 percent). Despite steroid therapy, the levels were persistently high. To our knowledge, this is the first report of an increased level of circulating gamma/delta T cells in a patient with eosinophilic granuloma.

Adult

Eosinophilic cationic protein in chronic eosinophilic pneumonia and eosinophilic granuloma.

We measured eosinophilic cationic protein (ECP) concentrations in the circulation and bronchoalveolar lavage (BAL) fluids from patients with chronic eosinophilic pneumonia, patients with eosinophilic granuloma, and normal control subjects. Significantly increased ECP concentrations were found in the circulation of patients with chronic eosinophilic pneumonia and with eosinophilic granuloma compared with those found in control subjects. The ECP concentrations were well correlated to eosinophil counts in the circulation of patients with chronic eosinophilic pneumonia, while they were not in patients with eosinophilic granuloma. Chronic eosinophilic pneumonia patients had prominently increased ECP concentrations in BAL fluids compared with those found in control subjects, while eosinophilic granuloma patients did not. Those concentrations in chronic eosinophilic pneumonia patients were well correlated to eosinophil counts in the BAL fluid. Corticosteroid therapy remarkably decreased circulating ECP concentrations in three patients with chronic eosinophilic pneumonia, but it had no significant effects in two patients with eosinophilic granuloma. Measurement of ECP concentrations seems to be useful to evaluate the disease activity of chronic eosinophilic pneumonia.

Adult

[Expression of integrin molecules in sarcoid lesions].

In order to assess the role of adhesion molecules in sarcoid lesions, we examined the expression of integrin families and extracellular matrix proteins by immunohistochemical techniques in sarcoid lymph nodes. Epithelioid cells exhibited intensive expression of ICAM-1, the alpha 5 and the beta 2 molecules. Lymphocytes exhibited intensive expression of ICAM-1, the alpha 4, the alpha 5 and beta 2 molecules. Laminin and type IV collagen were detected at basement membranes in vessels. Fibronectin was distributed within granulomas with a concentric pattern and around granulomas with a fibrillar pattern. Its distribution was well correspondence with the alpha 5 expression. These data suggest that integrin families might play an important role in granuloma formation and migration of lymphocytes into inflamed sarcoid lesions.

Cell Movement

[A case of pulmonary sarcoidosis with B lymphocytosis in peripheral blood].

A 24-year-old man was admitted on October 14, 1988, with bilateral cotton-like shadows on chest X-ray film. Chest CT demonstrated multiple nodular shadows in bilateral lung fields. Laboratory data on admission showed peripheral blood lymphocytosis and slight decrease of serum IgG and IgA. ACE was within normal limits, and BALF findings showed no increase of lymphocytes. Surface marker analysis of peripheral blood lymphocytes showed an increase of B lymphocytes of antibody independent stage (B1, B4, J5, OKB7, sIgM, and sIgD positive cells were increased). Southern blot analysis of peripheral blood showed no rearrangement of immunoglobulin chains (H chain and L chain). In order to differentiate sarcoidosis from lymphoproliferative disorder, open lung biopsy was performed. Pathologic study revealed multiple epithelial granulomas without caseation. Immunohistochemical study demonstrated no accumulation of B cells of the lung. This patient was pathologically diagnosed as having pulmonary sarcoidosis. The abnormal chest shadows gradually improved without therapy; however, B cell lymphocytosis and slight decrease of serum IgG and IgA persisted. In general, lymphocytopenia of peripheral blood is usual in sarcoidosis. We report a rare case of pulmonary sarcoidosis with polyclonal B lymphocytosis of antibody independent stage in peripheral blood.

Adult

[A case of the management of developed collateral vessels through left thoracotomy of recurrence of right bronchiectasia with hemoptysis].

A 40-year-old woman, with a previous history of right S1, S2 segmentectomy and right middle lobectomy for bronchiectasis with hemoptysis at the age of 24, was admitted for frequent hemoptysis. As a result of a chest roentgenogram, a CT scan and bronchographic examination, a recurrence of bronchiectasis in the right ventral segment of the upper lobe (S3) and the right superior segment of the lower lobe (S6) was diagnosed. The bronchial arteriogram and aortogram showed four vessels going into this region and a shunt lesion was located on located on the proximal side of the pulmonary artery. If a right pneumonectomy had been done, pulmonary function would have gotten worse. If a right thoracotomy had been performed, there would have been much bleeding from the entering vessels. Therefore, a left thoracotomy was preformed and those vessels ligated. The patient is doing well one year after the operation without hemoptysis.

Adult

A case of Trichosporon pullulans infection of the lung with adult T-cell leukemia.

Fungal infections are often reported, but Trichosporon infection is very rare. A 78-year-old man with adult T-cell leukemia complicated with pulmonary infections is presented. Bronchial exudate culture revealed many yeast-like colonies, which were morphologically and biochemically identified as Trichosporon pullulans.

Aged