The 150-kilodalton oxygen-regulated protein ameliorates lipopolysaccharide-induced acute lung injury in mice.

The 150-kd oxygen-regulated protein is a novel stress protein that is located in the endoplasmic reticulum and contributes to cell survival when this organelle is under stress. Expression of this protein was strongly increased in alveolar macrophages and alveolar epithelial cells from mice with acute lung injury induced by lipopolysaccharide. Transgenic mice overexpressing the 150-kd protein showed decreased histological severity of this lung injury, accompanied by lower total protein concentrations, and lactate dehydrogenase activity in bronchoalveolar lavage fluid. As indicated by nick end-labeling, lipopolysaccharide induced apoptosis in fewer alveolar wall cells in transgenic than in wild-type mice. Transgenic mice also showed increased survival after lipopolysaccharide injection (a log-rank test). Thus, the 150-kd protein, an endoplasmic reticulum-related molecular chaperone, is pivotal in resisting acute lung injury from lipopolysaccharide.

[A case of tricuspid valve infective endocarditis presenting with multiple nodular shadows in both lungs without known predisposing factors].

A 56-year-old woman was admitted to our hospital with fever, cough, and sputum production. Her chest radiograph and chest computed tomography showed multiple nodules. Laboratory findings revealed leukocytosis and an increased C-reactive protein concentration. Physical examination revealed a systolic murmur. Transesophageal echocardiography demonstrated a 1.5-cm area of vegetation on the tricuspid valve. Blood cultures grew Staphylococcus aureus. Tricuspid valve endocarditis and septic pulmonary embolism were diagnosed. She was treated successfully with intravenous ampicillin/sulbactam. This was a rare case of tricuspid valve infective endocarditis in an adult patient without known predisposing factors.

Allergic bronchial asthma: airway inflammation and hyperresponsiveness.

The international consensus report on diagnosis and treatment of asthma was published in 1992 (Clin Exp Allergy 22: 1-72). According to the report, asthma is a chronic inflammatory disorder of the airways in which many cells play a role, including mast cells and eosinophils. Airway inflammation causes various symptoms of asthma which are usually associated with widespread but variable airflow obstruction and causes an associated increase in airway responsiveness to a variety of stimuli. The definition of asthma, provided in this report, is an epoch-making revision of the conventional recognition of asthma based on respiratory physiology and does not contradict the empirical knowledge that asthma responds well to steroid therapy. One reason, which led airway inflammation to be understood as a major factor in the pathophysiology of asthma is the technological advance and the widespread use of bronchoscopes. The use of bronchoscopy as a research tool has markedly improved the understanding of the pathology of asthma. It became also possible to link biopsy findings to autopsy findings in patients who died of asthma. However, it is relatively difficult to repeat a biopsy of the airway mucosal membranes in individual asthmatic patients. Here, animal models of asthma play a significant role. Findings from animal models can provide a clue for the development of new anti-asthmatic drugs. This paper will deal with the paradigm of allergic asthma and focus on recent topics of interleukin (IL)-4 and IL-5, which seem to play a central role in allergic asthma. The causative relationship between airway inflammation and hyperresponsiveness will be discussed.

[Expression of heme oxygenase-1 and its effects in allergic airway inflammation and hyperresponsiveness].

We investigated whether an expression of hemeoxygenase-1 (HO-1) within the lung tissue is related to allergic airway inflammation and HO-1 expression could influence airway hyperreactivity (AHR) and eosinophilia in C57BL/6 mice actively sensitized to ovalbumin. The number of HO-1 positive cells was increased in the subepithelium of the bronchi after OVA challenge and HO-1 was localized to alveolar macrophage.Zinc-protoporphyrin (Zn-PP), a competitive inhibitor of hemeoxygenase, by intraperitoneal injection clearly inhibited AHR, pulmonary eosinophilia and IL-5 and IL-13 in the lung tissue. These data indicate that the expression of HO-1 is increased within the lung tissue in allergic airway inflammation and the overexpression of HO-1 could enhanced allergic airway inflammation.

[An autopsy case of desmoplastic malignant mesothelioma].

On November 15, 2000, a 60-year-old man was admitted to our hospital with progressive dyspnea and right chest pain. He had a 40-year history of occupational asbestos exposure, which began when he was 20 years old. On admission, his chest radiographs showed pleural effusion on the right side, and asbestos bodies were detected in his sputum. Neither a cytological examination of the pleural effusion nor a histological examination of the pleura by percutaneous pleural biopsy revealed malignant cells. In addition, we could not find any other cause for the pleural effusion (such as tuberculosis, collagen disease, or heart failure). In May 2001, the patient also developed pleural thickening and pain in the right hypochondrium, and he was readmitted to our hospital on May 21, 2001. On readmission, an enhanced abdominal CT showed multiple liver tumors, and percutaneous pleural and liver biopsies were performed. The histological findings in the pleura and liver specimens revealed hypocellular collagen tissues without malignant cells. Thus, we could not determine the main cause either of the pleural effusion or of the patient's disease. However, his condition rapidly deteriorated, and he died on August 12, 2001. At the autopsy, bilateral pleural thickening, predominantly on the right side, and invasion of the lungs were observed. The histological findings in the pleural and hepatic tissues revealed hypocellular collagen fibers with a striate pattern and areas of neoplastic spindle cells. He was diagnosed as having malignant desmoplastic mesothelioma with liver metastasis. Cases of malignant desmoplastic mesothelioma have rarely been reported in Japan.

[A case of pulmonary sarcoidosis with pneumothorax and pleural effusion after improvement of pulmonary impairment].

A 23-year-old man was admitted to our hospital for a complete medical evaluation of abnormal pulmonary shadows found on a chest radiograph during his annual check-up. Chest radiography and chest CT showed a diffuse spread of micronodules in both lung fields and mediastinal lymphadenopathy. A transbronchial lung biopsy demonstrated evidence of noncaseating epithelioid cell granuloma with multinucleated giant cells, and a diagnosis of sarcoidosis was made. The pulmonary shadows improved without therapy. Twenty months later, the patient was readmitted to the hospital because of chest pain and dyspnea. Pneumothorax appeared on the right in a chest radiograph, but subsided after drainage therapy, and two weeks later, a right side pleural effusion was seen. We determined that the pleura was involved in the sarcoidosis, and the patient was treated with oral prednisolone 20 mg daily. The pleural effusion gradually subsided. This is the first reported case in Japan of pulmonary sarcoidosis with pneumothorax and pleural effusion after improvement of pulmonary impairment.

[A case of desmoplastic malignant mesothelioma with elevated serum CYFRA 21-1].

A 70-year-old woman was admitted to our hospital for medical evaluation of a right side pleural effusion, which was pointed out at another hospital. Chest CT revealed a right pleural effusion with diffuse and irregular pleural thickening. Percutaneous pleural biopsy showed hypocellular collagenous tissue without malignant cells. Though she received antituberculosis therapy, the pleural thickening progressed and the serum CYFRA 21-1 level was elevated. Chest pain and dyspnea appeared, and she was readmitted. However, pneumonia was present as a complication, and she died. At autopsy, the right pleura was thickened and invasion of the lung and the chest wall was observed. Microscopic findings showed increased amounts of hyalinized collagen fibers forming a storiform pattern. At the tumor foci, atypical cells with distinct nucleoli were observed. Desmoplastic malignant mesothelioma, which is rarely reported in Japan, was diagnosed.

[An autopsy case of protein-losing enteropathy due to gastrointestinal amyloidosis, occurring in empyema].

On August 14, 2001, a 76-year-old woman with a history of rheumatoid arthritis was admitted to our hospital with fever, cough, dyspnea and diarrhea. On admission, her chest radiography showed pleural effusion on the right side, and thoracocentesis was used to diagnose empyema. The patient underwent pleural drainage and received antibiotics. Alpha-Streptococcus was detected in both aerobic and anaerobic cultures of the pleural effusion. After 2 weeks of therapy, her empyema had improved; but her diarrhea, which had started 1 week before admission, had worsened, and her hypoproteinemia had progressed. Examination of the fecal clearance of alpha-1-antitrypsin and biopsied rectal material revealed that the diarrhea was caused by protein-losing enteropathy due to gastrointestinal amyloidosis secondary to rheumatoid arthritis. The patient was treated with steroids, but developed an additional infectious disease and died on September 29, 2001. In this case, she suffered from various infectious diseases including empyema and fungus infections. It has been reported that protein-losing enteropathy accompanies abnormalities in the immune system, by the loss of immunoglobulins and lymphocytes from the gut. We therefore suspect that protein-losing enteropathy due to gastrointestinal amyloidosis caused this patient's empyema.

[A case in which progressive emphysematous changes were seen on chest computed tomography associated with Pneumocystis carinii pneumonia in a patient with AIDS].

A 60-year-old man was admitted to our hospital complaining of progressive dyspnea. On admission, he had marked hypoxemia, and his chest radiography and computed tomography (CT) showed ground glass opacities and multiple emphysematous changes in both lung fields. On examining the patient's bronchoalveolar lavage fluid (BALF). Pneumocystis carinii pneumonia (PCP) was diagnosed. A serological test for human immunodeficiency virus (HIV)-1, 2 was positive, and acquired immunodeficiency syndrome (AIDS) was diagnosed. Since the chest CT performed a month before the patient's admission to our hospital revealed ground glass opacities in both lung fields we thought that he had already developed PCP at that time. In comparison with his previous CT, the chest CT on admission showed progressive ground glass opacities and emphysematous changes. Although PCP is known to display various findings on chest radiography and CT, emphysematous changes are rarely reported in Japan. In this case we were able to confirm these changes and observe its progression using chest CT.

[A case of scurvy with alveolar hemorrhage].

A 53-yr-old man with a history of chronic renal failure was admitted to the hospital of Hyogo College of Medicine on March 24th, 1999, because of severe continuous hemoptysis. On February 14th, 1999, the patient had undergone a cadaveric kidney transplantation in the urology department of another hospital. He did not experience any immunological reactions due to tissue rejection. On admission, subcutaneous bleeding at the site of an injection received 1 month before was noticed on his left arm. Petecheae of the extremities and a conjunctival hemorrhage were also noted. However, coagulation and fibrinolysis tests were essentially normal. These findings indicated that the hemorrhages were due to vessel weakness. Scurvy was diagnosed since his serum vitamin C was extremely low (0.2 microgram/ml). The patient was given ascorbic acid (1 g/day), and his condition improved dramatically. Ten years ago, the patient had had renal failure, which had been treated with chronic maintenance dialysis and dietary restriction. It has been postulated that a diet lacking in vitamin C or the steroid treatment he received after kidney transplantation may have induced the scurvy.