Ichiro Yamadori

Ocular adnexal IgG4-related disease has uniform clinicopathology

IgG4‐related disease is a recently proposed clinical entity with several unique clinicopathological features. Ocular adnexal IgG4‐related disease, however, has not well been clarified. The purpose of the present study was to examine 21 patients (10 men, 11 women; age range, 39–86 years) with ocular adnexal IgG4‐related disease. In 17 out of 21 patients (81%), the lacrimal glands were involved and bilateral lacrimal gland swelling was frequently observed (n = 12; 70.6%). In contrast, the conjunctiva was not involved in any of the patient. Histology was uniform with marked lymphoplasmacytic infiltration admixed with dense fibrosis, similar to previous reports of IgG4‐related disease. Immunostaining detected numerous aggregates of IgG4‐positive plasma cells. Serum IgG4 was higher than normal in 10 of the 13 patients tested, although it was measured after treatment in almost all cases. Interestingly, immunoglobulin heavy chain gene rearrangement was detected in two of 17 patients (12%) examined. The present results show that ocular adnexal IgG4‐related disease has uniform clinicopathology: that is, disease involving the bilateral lacrimal glands with lymphoid hyperplasia and fibrosis, but not the conjunctiva. And presence of immunoglobulin heavy chain gene rearrangement suggests the possibility of B‐cell lymphoma arising in a background of IgG4‐related chronic inflammation.

Pathological and radiological changes in resected lung specimens in Mycobacterium avium intracellulare complex disease

The present study was designed to evaluate the pathological and immunohistochemical findings of Mycobacterium avium intracellulare complex (MAC) lung infection. A retrospective study was performed in five cases with positive cultures for MAC in whom lung resections were performed between January 1989 and December 1996. A determination of whether or not MAC caused pulmonary disease was made using the 1997 criteria defined by the American Thoracic Society. In addition, MAC was cultured from all of the five lung specimens. Pathological and immunohistochemical findings as well as chest computed tomography (CT) findings were evaluated in these five patients. Pathological findings of bronchiectasis, bronchiolitis, centrilobular lesion, consolidation, cavity wall and nodules were demonstrated, respectively, in relation to chest CT findings. Extensive granuloma formation throughout the airways was clearly demonstrated. Immunohistochemical staining demonstrated: 1) epithelioid cells and giant cells; 2) myofibroblasts extensively infiltrating the cavity wall; and 3) B-cells detected in aggregates in the vicinity of the epithelioid granulomas. This study identified pathological and immunohistochemical characteristics of Mycobacterium avium complex infection relative to chest computed tomography findings and allowed the conclusion that bronchiectasis and bronchiolitis were definitely caused by Mycobacterium avium complex infection.

Clinical features of Stenotrophomonas maltophilia pneumonia in immunocompromised patients

Between January 1988 and December 1992, 68 patients admitted to our Department of Internal Medicine with haematological malignancies or solid tumours showed colonization of the respiratory tract with Stenotrophomonas maltophilia. To characterize the significance of respiratory tract colonization by S. maltophilia, we retrospectively reviewed the medical records of the 68 patients colonized with this organism. Twenty-nine of these 68 patients developed pneumonia, with S. maltophilia being implicated in 10 cases. The majority of these 10 patients showed lobular infiltration on chest X-ray. Pleural effusion was observed in two (20%) of the 10 patients. All 68 strains of S. maltophilia were resistant to imipenem. Latamoxef was effective against 98 center dot 5% of strains, while minocycline was effective against 100% of strains. This report describes the clinical features of nosocomial S. maltophilia pneumonia in immunocompromised patients.

Nonspecific interstitial pneumonia as pulmonary involvement of primary Sjögren's syndrome.

Abstract. The pathologic patterns of lung involvement in nine patients with Sjögrens syndrome (SjS) are evaluated. The patients consisted of three males and six females, with a median age of 59 years. The SjS was diagnosed according to the criteria of the First International Seminar on SjS. In all patients, high-resolution computed radiographic scanning (HRCT) of the lungs was performed, and apparent honeycomb or microhoneycomb formation was observed in six patients. Pathologically, six patients were diagnosed with usual interstitial pneumonia (UIP), and three were diagnosed with nonspecific interstitial pneumonia/fibrosis (NSIP) (group II). There were no apparent honeycomb formations on HRCT in patients diagnosed with NSIP. In conclusion, NSIP is also a possible histologic classification of interstitial pneumonia associated with SjS.

Clinical features of non-specific interstitial pneumonia

The clinical features of 24 patients with non-specific interstitial pneumonia (NIP) were evaluated. The patients consisted of seven men and 17 women, with a median age of 60 years. In seven patients, the disease was idiopathic and eight had collagen vascular diseases. Cough, dyspnoea and fever were frequently observed. The time interval between the onset of symptoms and open lung biopsy was 3 months. Mild increases of IgG, CRP, and LDH were also frequently observed. The average per cent VC was 65.1 +/- 3.2% and the average PaO2 was 71.3 +/- 2.4 Torr. Bronchoalveolar lavage was done in 20 patients, and a moderate increase in lymphocytes (27.8 +/- 6.7%) with a low CD4/CD8 ratio (0.86 +/- 0.22) was observed. Multiple patchy infiltration or diffuse interstitial shadows, located predominantly in the lower fields of both lungs were the characteristic chest CT findings. Lung biopsies in this group were characterized by varying proportions of chronic interstitial inflammation and fibrosis which was temporarily uniform. Patients were given steroid pulse therapy or oral steroids. The results were mild to marked improvements in chest roentgenographic findings and lung functions. Four patients (16.7%) died because of respiratory failure caused by NIP. This is the first report to describe clinical features of NIP since the original report by Katzenstein and Fiorelli.

Pathological findings of bronchiectases caused by Mycobacterium avium intracellulare complex

It has been argued whether bronchiectasis is truly caused by MAC infection or just a predisposed condition in which MAC colonizes. Our present study was designed to evaluate the pathological findings of bronchiectases caused by Mycobacterium avium intracellulare complex (MAC) lung infection and to demonstrate MAC in the lesion of bronchiectases. A retrospective study was performed in nine cases with positive cultures for MAC in whom lung resections were performed. A determination of whether or not MAC caused pulmonary disease was made using the 1997 criteria required by the American Thoracic Society. In addition, MAC were cultured from all nine lung specimens. Pathological findings of bronchiectases were evaluated in these nine patients. Destruction of bronchial cartilage and smooth muscles layer, obstruction of airway by granulomas, and ulceration of bronchial mucosa were frequently observed. Our present study demonstrates that destruction of fundamental bronchial structure due to extensive granuloma formation throughout the airways was likely the main cause of bronchiectases in MAC infection.

Heterogeneous point mutations of the p53 gene in pulmonary fibrosis

Lung cancer is a frequent complication in pulmonary fibrosis. Overexpression of p53 proteins has been demonstrated by immunostaining in bronchoepithelial cells in patients with idiopathic pulmonary fibrosis. However, it is still unclear whether this overexpressed p53 protein is wild-type or mutant. It was hypothesized that pulmonary fibrosis may be a precancerous lesion with deoxyribonucleic acid point mutations in bronchoepithelial cells. Mutations of the p53 gene were tested for by fluorescence-based single-strand conformation polymorphism (FSSCP), cloning-sequencing and immunostaining techniques. Out of 10 tissue samples that demonstrated overexpression of p53 protein by immunostaining, nine (90%) exhibited point mutations and eight (80%) exhibited heterogeneous point mutations of the p53 gene. The mutations found in pulmonary fibrosis were scattered throughout the central part of the p53 gene, and both guanine (G):cytosine (C) to adenine (A):thymine (T) and A:T to G:C transitions were frequently observed. In conclusion, frequent heterogeneous point mutations of the p53 gene were detected in pulmonary fibrosis. These mutations may have resulted from several types of deoxyribonucleic acid damage that occurred in bronchoepithelial cells and this may explain previous findings of a very high incidence of lung cancer complicating pulmonary fibrosis.

Lymphocyte subsets in lung tissues of interstitial pneumonia associated with untreated polymyositis/dermatomyositis

Abstract. This study was designed to evaluate the distribution of lymphocyte subsets in lung specimens obtained by surgical lung biopsy from 12 patients with interstitial pneumonia associated with untreated polymyositis/dermatomyositis (PM/DM). Differences of histological findings and distributions of lymphocyte subsets between PM and DM were also evaluated. Distributions of B lymphocytes, CD4-positive T lymphocytes, and CD8-positive T lymphocytes were evaluated immunohistochemically. Interstitial pneumonia was pathologically classified as basically nonspecific interstitial pneumonia (NSIP) in all patients. Immunohistochemically, the distribution of B lymphocytes was mostly restricted to inside and/or around lymphoid follicles. The CD4-positive T lymphocytes were distributed diffusely in fibrotic areas and unrelated to lymphoid follicles. Most CD8-positive T lymphocytes were diffusely distributed, especially in relatively normal alveoli. There were no significant differences in the distribution of lymphocyte subsets between PM and DM. Although the distribution of B lymphocytes and CD4- and CD8-positive T lymphocytes in the lung were different, there were no significant differences in distributions of lymphocyte subsets between PM and DM.

Measurement of hepatocyte growth factor in serum and bronchoalveolar lavage fluid in patients with pulmonary fibrosis

The present study evaluated the clinical significance of hepatocyte growth factor (HGF) in patients with pulmonary fibrosis. Twenty-one patients with a diagnosis of pulmonary fibrosis [14 with idiopathic pulmonary fibrosis (IPF) and seven with pulmonary fibrosis associated with a collagen vascular disorder (PF-CVD]) and 21 normal subjects as control were studied. HGF levels in sera of patients with pulmonary fibrosis (0.34 +/- 0.02 ng ml-1) were elevated significantly as compared with normal subjects (0.21 +/- 0.01 ng ml-1) (P < 0.0001). HGF/albumin levels in broncho-alveolar lavage fluid (BALF) of patients with pulmonary fibrosis (72 +/- 17 ng g-1 albumin) were also significantly elevated as compared with normal subjects (under the detection limit) (P < 0.01). HGF levels in sera correlated significantly with elastase levels in sera and C-reactive protein, and correlated negatively with PaO2. HGF levels in sera were significantly higher in smokers with pulmonary fibrosis (0.42 +/- 0.03 ng ml-1) as compared with non-smokers with pulmonary fibrosis (0.29 +/- 0.03 ng ml-1) (P < 0.005). HGF/albumin levels in BALF correlated significantly with elastase/albumin levels in BALF, lactate dehydrogenase/albumin in BALF, Immunoglobulin A/albumin in BALF, total cell count/albumin in BALF, total number of alveolar macrophage/albumin in BALF, total number of neutrophil/albumin in BALF, CEA/albumin in BALF, CA19-9/albumin in BALF, and SCC/albumin in BALF. These results suggest that following lung injury, HGF may be a mediator involved in the repair which leads to pulmonary fibrosis.

Characterization of a small-cell-lung-carcinoma cell line from a patient with cancer-associated retinopathy.

We examined the biologic properties of a small‐cell‐lung‐carcinoma (SCLC) cell line (designated MN‐1112) established from a patient with SCLC who showed paraneoplastic retinopathy syndrome. Morphologic and immunocytochemical analyses showed that MN‐1112 cells possess features of the classic type of SCLC. MN‐1112 cells grew in suspension forming relatively large clumps of cells with a doubling time of 72 hr. By light‐microscope examination, the cells were relatively small and had scanty cytoplasm. The cells produced NSE, ACTH and CK (BB isozyme); they also expressed recoverin, a novel photoreceptor protein, detected by Northern‐blot and Western‐immunoblot analysis using human‐recoverin‐specific DNA probe and anti‐bovine‐recoverin polyclonal antibody. This report shows that human recoverin is expressed in cultured SCLC cells. Our results support the hypothesis that, in cancer‐associated retinopathy (CAR) patients, auto‐immune antibody targeting for ectopic recoverin in SCLC is initially produced and cross‐reacts with the retinal protein, resulting in the retinal degeneration that occurs in CAR patients.