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Biomedical subjects

S Imokawa

Publications and source records attributed to S Imokawa.

At least 19 recordsLinked to original sources

Lack of evidence for a role of Epstein-Barr virus in the increase of lung cancer in idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is known as an independent risk factor for lung cancer. Because Epstein-Barr virus (EBV) may be involved in the genesis of IPF as well as certain malignancies, we investigated whether EBV contributes to the increased incidence of lung cancer in IPF The formalin-fixed and paraffin-embedded lung sections were prepared from 22 lung cancer patients with IPF and 22 lung cancer patients without IPF All ofthe IPF patients pathologically showed usual interstitial pneumonia. In situ hybridization for EBV-encoded small non-polyadenylated RNAs failed to show positive signals in the cancer tissues of either IPF or non-IPF patients. This study did not provide evidence for an etiologic role of EBV in the development of lung cancer in IPF.

Adenocarcinoma↗

Wegener's granulomatosis responding to antituberculous drugs.

We present a case of Wegener's granulomatosis (WG) that responded to antituberculous drugs. A 44-year-old woman with multiple nodules on chest radiograph received a diagnosis of pulmonary tuberculosis because open-lung biopsy specimens showed caseous granulomas. Her chest shadows underwent repeated resolution after the start of antituberculous treatment, and relapse after the cessation of the drugs. Antineutrophil cytoplasmic antibody was positive (14 enzyme-linked immunosorbent assay units), and the second lung biopsy specimens showed necrotizing granulomas and vasculitis without pathogenic organisms. Thus, the patient received a diagnosis of WG and was successfully treated with trimethoprim/sulfamethoxazole 10 years after her initial evaluation. Antituberculous drugs were effective in this case of WG.

Adult↗

Methotrexate pneumonitis: review of the literature and histopathological findings in nine patients.

Pneumonitis is a serious and unpredictable side-effect of treatment with methotrexate (MTX) that may become life-threatening. The clinical and histological features of nine cases of MTX pneumonitis are reported and the literature reviewed. The typical clinical symptoms include progressive shortness of breath and cough, often associated with fever. Hypoxaemia and tachypnoea are always present and crackles are frequently audible. Chest radiography reveals a diffuse interstitial or mixed interstitial and alveolar infiltrate, with a predilection for the lower lung fields. Pulmonary function tests show a restrictive pattern with diminished diffusion capacity. Lung biopsy reveals cellular interstitial infiltrates, granulomas or a diffuse alveolar damage pattern accompanied by perivascular inflammation. These clinical and pathological findings are not specific to MTX pneumonitis and can be seen with other drug-induced lung toxicities. It is important that all patients receiving methotrexate be educated concerning this potential adverse reaction and instructed to contact their physicians should significant new pulmonary symptoms develop while undergoing therapy. If methotrexate pneumonitis is suspected, methotrexate should be discontinued, supportive measures instituted and careful examination for different causes of respiratory distress conducted.

Aged↗

[Aspergillosis with non-cavitary lung cancer].

Growth of Aspergillus was observed in the necrotic tissue of non-cavitary lung cancer. Case 1 was a 60-year-old male complaining of cough and fever and was found to have left lower lobe atelectasis on chest X-ray. Bronchoscopic examination showed the yellow soft lesion occluding the left upper and lower lobe bronchus. Specimen from the lesion demonstrated adenocarcinoma and hyphae of Aspergillus in the necrotic tumor. Case 2 was a 53-year-old male who was found to have a left upper lobe mass by chest X-ray screening. Bronchoscopic examination showed the yellow polypoid lesion occluding the left upper division bronchus. Pneumonectomy was done and resected specimen of the lesion demonstrated adenocarcinoma and the hyphae of Aspergillus growing in both necrotic tissue and cancer tissue. As both patients had hyphae of Aspergillus in the necrotic tumor, it is considered that the presence of necrosis may cause the growth of Aspergillus.

Adenocarcinoma↗

Increased numbers of dendritic cells in the bronchiolar tissues of diffuse panbronchiolitis.

Dendritic cells (DCs) are potent antigen-presenting cells (APCs); they are considered to be the most important APC in the lung. Recently, the number of DCs in the large airways was demonstrated to increase in patients with atopic asthma, leading to the concept that DCs play an important role in airway inflammation. However, little is known about the distribution of lung DCs in the small airways under other pathological conditions. The aim of the present study was to examine the distribution of DCs in the bronchiolar tissues in patients with diffuse panbronchiolitis (DPB), which is a chronic inflammatory disorder of the airways histologically characterized by peribronchiolitis. We investigated the distribution of DCs in the bronchiolar tissues of the lungs in 11 patients with DPB and 7 control subjects with normal lungs using immunohistochemical methods. Marked increases in the number of CD1a(+), CD1c(+), and CD83(+) DCs were found in both the bronchiolar epithelium and submucosal tissues of patients with DPB, compared with control subjects with normal lungs. The most striking increase occurred in the number of DCs expressing CD83, a marker of mature DCs, in the submucosal tissues of patients with DPB. The increases of these positive cells in patients with DPB were more marked in the submucosal tissues than in the epithelium. The bronchiolar epithelial cells in patients with DPB strongly expressed GM-CSF protein, which is an important cytokine for the differentiation and function of DCs, suggesting that the increased local production of GM-CSF may be responsible for the accumulation and differentiation of DCs in the bronchiolar tissues of patients with DPB. These results suggest that increased DCs in the bronchiolar tissues, together with their phenotypical maturation, may play an important role in the mucosal immune response in patients with DPB through their potent antigen-presenting function.

Adult↗

[Testicular sarcoidosis].

We report a rare case of testicular sarcoidosis. A 68-year-old man was admitted for detailed examination of uveitis and swelling of the testes. A chest X-ray film and computed tomographic scans disclosed ground-glass shadows in the lower fields of both lungs with mediastinal lymphadenopathy. Ga scintigram showed pronounced accumulations in the testes, hilum, and mediastinum. Transbronchial lung and testicular biopsy specimens demonstrated noncaseating epithelioid granulomas, thus confirming the diagnosis of sarcoidosis with testicular involvement. The patient was followed up without systemic steroids. A review of the world literature found only 12 reported cases of clinically evident testicular sarcoidosis.

Aged↗

[Lung cancer obscured by aspergillus hyphae].

A 66-year-old man was referred to our hospital because of cough. Chest X-ray films showed complete atelectasis of the left lung. Serum CYFRA was elevated. Bronchoscopic examination disclosed a white polypoid lesion occluding the left main bronchus. A biopsy specimen from the lesion revealed numerous aspergillus hyphae. Oral itraconazole (100 mg) and weekly endobronchial instillation of fluconazole were administered. Three months later, on the 12th bronchoscopic examination, the tumor occluding the left main bronchus was detected after the removal of aspergillus, and the biopsy findings yielded a diagnosis of squamous cell carcinoma. Aspergillosis complicated by lung cancer without cavity formation is very rare, and compounded the difficulty of diagnosing lung cancer in this case.

Aged↗

[A comparative study of the prognosis for Japanese patients with idiopathic interstitial pneumonia or BOOP based on histopathologic subsets].

We explored the prognosis for 123 patients with either idiopathic interstitial pneumonia (IIP) or bronchiolitis obliterans organizing pneumonia (BOOP). All patients underwent either open lung biopsy or thoracoscopic lung biopsy procedures. The histopathologic diagnosis of IIP included patients with usual interstitial pneumonia (UIP), nonspecific interstitial pneumonia (NSIP), and desquamative interstitial pneumonia with respiratory bronchiolitis-associated interstitial lung disease. The prognosis was poorest for patients with a histologic diagnosis of UIP, and excellent for those who received a diagnosis of BOOP. Although the prognosis is generally considered to be good for patients with NSIP, some NSIP patients in our study died. Histopathologic diagnosis based on surgical lung biopsy is useful in evaluating the prognosis for patients with IIP.

Aged↗

[A case of tracheobronchomegaly].

We report a rare case of tracheobronchomegaly with crescent-type tracheobronchomalacia. A 77-year-old man with a chronic cough was referred to our hospital because of fever and dyspnea. Radiographic examination showed enlargement of the trachea and main bronchi. On chest radiography, the transverse diameter of the trachea was 31 mm, and consolidation shadows were seen in both upper lung fields. Tracheobronchomegaly with pneumonia was diagnosed. The pneumonia was improved by administration of PAPM/BP. On bronchoscopic examination, the trachea and main bronchi were extremely dilated on inspiration, and were collapsed on expiration. The biopsy specimen from the bronchial mucosa showed non-specific chronic inflammation.

Aged↗

[Compensatory growth of residual lung after pneumonectomy in childhood].

Though pneumonectomy proved to be a potent stimulus to compensatory growth in the animal model, the literature on this subject in human patients is sparse. We report a rare case of compensatory growth after pneumonectomy in childhood. A 17-year-old man was admitted to our hospital because of chest pain. He had been capable of normal exercise despite a history of pneumonectomy at the age of 4. Chest radiography showed pneumothorax and a displaced heart. In a chest CT scan, both pleural spaces were filled with the enlarged left lung. Since thoracoscopic examination showed a bulla at the surface of S3, bullectomy was performed. The specimen resected from the lung showed slight dilatation of the alveoli. It is considered that the enlargement of the residual lung had occurred as a result of alveolar multiplication rather than by dilatation of the existing alveoli. This case demonstrates lung regeneration in childhood.

Adolescent↗

Development of bronchus-associated lymphoid tissue in chronic hypersensitivity pneumonitis.

STUDY OBJECTIVES: Bronchus-associated lymphoid tissue (BALT) is well defined in animals. In humans, however, BALT has been reported to be inducible under pathologic conditions, such as chronic respiratory infection, although it is not present in healthy adults. Thus, induced BALT is considered to be involved in the mucosal immunity of the human lung under these conditions. However, there have been few studies to investigate BALT development in hypersensitivity pneumonitis. The aim of this study was to examine the presence of BALT in hypersensitivity pneumonitis, especially in its chronic form. METHODS: The subjects included five patients with chronic hypersensitivity pneumonitis (CHP) diagnosed from clinical and histologic findings. We investigated histologically the development of BALT in these patients. Further, the cellular distribution of BALT was also examined by immunohistochemistry. RESULTS: BALT was present in three of five patients with CHP. Immunohistochemical examination revealed the follicular area of BALT to be composed mainly of B cells, while the parafollicular area comprised predominantly T cells. Centroblasts located in the germinal center of BALT expressed Ki-67 antigen, a marker of cell proliferation, suggesting that these cells were actively proliferating after antigenic stimulation. Cells expressing bcl-2, which is present primarily on memory B cells, were confined to the follicular area, devoid of any germinal centers. S-100-positive, CD1a-negative interdigitating dendritic cells were observed in the dome area of BALT. CONCLUSIONS: These observations suggest that chronic antigenic stimulation and/or inflammation in CHP may cause BALT development, which, in turn, is likely to play an important role in the mucosal immune response of this disease.

Adult↗

[Recurrent pulmonary infarction associated with familial protein S deficiency type III].

A 38-year-old woman was admitted to our hospital because of recurrent chest pain and fever. Chest X-ray films and computed tomograms showed subpleural consolidation containing small cavity-like opacities. Open lung biopsy revealed non-infectious abscess and vessels with organizing thrombus. The patient was given a diagnosis of pulmonary infarction due to the existence of deep venous thrombosis. Coagulation studies demonstrated that she had decreased plasma protein S activity, whereas her free and total protein S antigen levels were normal. Because her mother and maternal uncle and aunt also demonstrated decreased protein S activity with normal plasma protein S antigen levels, the patient was considered to be affected by familial protein S deficiency type III.

Adult↗

Diffuse panbronchiolitis and rheumatoid arthritis-associated bronchiolar disease: similarities and differences.

There is a considerable overlap between diffuse panbronchiolitis (DPB) and bronchiolar disease associated with rheumatoid arthritis. The present study assessed how these conditions could be differentiated. The subjects included 25 DPB patients and 15 RA patients with bronchiolar disease (RA-BD). Patients with either condition had chronic cough, purulent sputum, dyspnea and coarse crackles. Most patients with either DPB or RA-BD had a history of sinusitis as well as elevated cold hemagglutin titers and decreased levels in partial pressure of oxygen (PaO2), forced expiratory volume in one second (FEV1.0) and V 25/Ht. On histological examination, both conditions also shared various histological patterns although panbronchiolitis lesions were more common in DPB than RA-BD (68% vs 20%) and bronchiolar obliteration appeared to occur at more proximal sites in RA-BD than DPB. However, there were important differences: long-term treatment with erythromycin had less effect in RA-BD than DPB, and the frequency of HLA B54 tended to be higher in DPB than RA-BD (50.0% vs 22.2%), suggesting that they are distinct conditions.

Adult↗

[Interstitial pneumonia preceding systemic sclerosis].

We describe a 57-year-old man with interstitial pneumonia associated with systemic sclerosis. About 3 years prior to the appearance of distinctive signs of systemic sclerosis, he was admitted to our hospital with a chronic dry cough. A chest roentgenogram on admission revealed reticulonodular shadows in both lung fields. There were no abnormal laboratory findings. Open lung biopsy specimens revealed patterns indicative of usual interstitial pneumonia, and myxomatous connective tissue within the lumen of the airways. Skin biopsy specimens showed heightened levels of collagen in the dermis, a finding consistent with systemic sclerosis. The patient was given a diagnosis of lung involvement preceding systemic sclerosis despite the absence of concurrent skin symptoms.

Cryptogenic Organizing Pneumonia↗

Tissue factor expression and fibrin deposition in the lungs of patients with idiopathic pulmonary fibrosis and systemic sclerosis.

Although abnormalities of alveolar fibrin turnover have been reported to play a role in the development of idiopathic pulmonary fibrosis (IPF), the pathophysiological relevance remains unclear. We therefore investigated the localization of tissue factor (TF) and fibrin deposition in patients with IPF using immunohistochemistry and compared the results with those from patients who had interstitial pneumonia associated with systemic sclerosis (IP-SSc) and idiopathic bronchiolitis obliterans with organizing pneumonia (BOOP). Expression of TF-mRNA was also assessed, using in situ hybridization with a digoxigenin-labeled cRNA probe. In patients with IPF, IP-SSc, and idiopathic BOOP, the TF antigen was positively stained in type II pneumocytes and in some alveolar macrophages. The fibrin antigen was stained in the type II pneumocytes and the adjacent area. Tissue factor-mRNA was expressed in the type II pneumocytes and in some alveolar macrophages. Neither TF antigens nor TF-mRNA were detected in the normal lung. These results indicate that type II pneumocytes are a major source of TF, suggesting that TF production in these cells is closely related to fibrin deposition in the lungs of people with these diseases.

Base Sequence↗

[Clinicopathological features of interstitial pneumonia associated with amyopathic dermatomyositis].

We studied clinicopathological characteristics of interstitial pneumonia associated with amyopathic dermatomyositis. The subjects comprised two men and three women, and their mean age was 58.2 years. All subjects had cruptions specific for dermatomyositis, but had no signs of myositis. They all presented with acutely or subacutely developed coughing and dyspnea. Results of tests for anti-Jo-1 antibody were negative in all cases. Chest X-ray films showed infiltrations or streaky shadows, or both in the middle and lower lung fields. Analysis of bronchoalveolar lavage fluid revealed abnormally high percentages of lymphocytes and neutrophils. In one patients a specimen obtained by open lung biopsy showed homogeneous cell infiltrations in alveolar septa and regional alveolar damage. That patient was successfully treated with cyclosporin and corticosteroids in early phase of the disease. The other four patients received immunosuppressive agents after respiratory failure developed. All four died despite having received high-dose corticosteroid and immunosuppressive therapy. Examination of autopsy specimens showed diffuse alveolar damage.

Acute Disease↗

[Systemic sarcoidosis with involvement of the spermatic cord].

A 49-year-old man presented with an enlarging, painful, right inguinal mass and small red nodules around his nose and upper lip. He had undergone an operation for a right inguinal hernia in childhood. Because malignancy was suspected, the right spermatic cord, testis, and epididymis were resected. Histological examination of the lesion in the spermatic cord revealed non-caseating epithelioid-cell granuloma and no acid-fast bacilli, which was compatible with sarcoidosis. A chest X-ray film and computed tomograms showed enlarged hilar lymph nodes and reticular infiltrates. Histological examination of specimens obtained by transbronchial lung biopsy and by skin biopsy also showed non-caseating epithelioid-cell granulomas. After resection of the spermatic cord, the activity of angiotensin-converting enzume was 29.9 IU/L, which was above the reference range. Systemic sarcoidosis with involvement of the spermatic cord was diagnosed. Because he had no respiratory symptoms and his skin lesions resolved without treatment, he is currently under observation and is not receiving corticosteroid therapy.

Genital Diseases, Male↗

Possible involvement of an environmental agent in the development of acute eosinophilic pneumonia.

BACKGROUND: Although the pathogenesis of acute eosinophilic pneumonia remains largely unknown, it has been suggested that it may include a hypersensitivity phenomenon induced by inhaled environmental antigens. METHODS: To investigate this possibility, we studied the effect of environmental challenges in three patients with acute eosinophilic pneumonia. Symptoms and laboratory findings were evaluated before and after the challenge tests in the patient's homes and their places of work. RESULTS: After the provocation challenges to their homes, all three patients developed fever, cough, and fatigue and two of them presented with dyspnea. Inspiratory crackles became audible in all cases, and there was a decreased Pao2 level in two. Similar challenges at their workplaces were negative. After moving out of their homes, the patients engaged in their usual work but had no recurrent episodes. CONCLUSIONS: These results suggest that environmental factors in the home can be the cause of acute eosinophilic pneumonia. In order to elucidate the pathogenesis of the disease, it is important to further investigate environmental factors.

Acute Disease↗