Increased expression of matrix metalloproteinase in Clara cell-ablated mice inhaling crystalline silica.

We investigated the function of Clara cells in vivo during exposure to inhaled crystalline silica by examining pulmonary matrix metalloproteinase (MMP)-2 and MMP-9 mRNA levels in mice. The Clara cells of male FVB/n mice (8-12 weeks old) were ablated by intraperitoneal administration of naphthalene (300 mg/kg) in a corn oil vehicle. The mice were then exposed to crystalline silica (Min-U-Sil-5 silica, 97.1 +/- 9.5 mg/m(2), 6 hr/day, 5 days/week) for up to 2 weeks. Transcriptional levels of mRNA extracted from the lungs were assessed by reverse transcription-polymerase chain reaction. Gene expression of both MMP-2 and MMP-9 was significantly more marked in the Clara cell-ablated group than in the group with Clara cells, indicating that Clara cells inhibit MMP expression. Our findings suggest that Clara cells inhibit pulmonary inflammation induced by crystalline silica via MMPs in vivo.

Bilateral massive pleural effusions caused by uremic pleuritis.

A 61-year-old man was started on hemodialysis in June 1998. Just after the commencement of dialysis, a chest X-ray film revealed bilateral pleural effusions. The effusions were hemorrhagic and exudative, and did not respond to dialysis. He was transferred to our university hospital on October 8,1998. Repeated thoracentesis demonstrated hemorrhagic and exudative characteristics without any diagnostic evidence. Pleural biopsies showed fibrosis and lymphocyte infiltration. The effusions were massive and did not respond to treatments including hemodialysis, repeatedly performed pleurodesis and the administration of antituberculous drugs. He died of respiratory failure on December 30, 1998. The autopsy confirmed bilateral fibrinous pleuritis without any underlying infections or malignancy. We diagnosed this case as uremic pleuritis from this clinical course and the autopsy findings. The clinical entity of uremic pleuritis was recognized as a complication of patients with hemodialysis in 1969. Uremic pleuritis generally responds to continued hemodialysis and the prognosis is usually good. However, some case reports demonstrated that surgical decortication is only indicated in cases with a severe clinical course. The clinical course of the present case was progressive and fatal. Uremic pleuritis is a serious complication of hemodialysis, which may lead to death.

Effects of mineral fibers on the gene expression of proinflammatory cytokines and inducible nitric-oxide synthase in alveolar macrophages.

To determine which parameters are useful for the risk assessment of man-made mineral fibers (MMMFs), we examined the gene expression of interleukin-1 alpha (IL-1 alpha), tumor necrosis factor alpha (TNF alpha), interleukin-6 (IL-6) and inducible nitric-oxide synthase (iNOS) in mineral fiber-exposed alveolar macrophages (AMs). Male Wistar rats were intratracheally exposed to saline or mineral fibers suspended in saline (2 mg of crocidolite, chrysotile, alumina silicate refractory fiber (RF1) or potassium octatitanate whisker (TW)). Bronchoalveolar lavage was performed 4 weeks after the fiber-instillation, and the recovered AMs were stimulated by lipopolysaccharide for 2 or 6 hours. Expression of IL-1 alpha, TNF alpha, IL-6 and iNOS from AMs was observed using reverse transcription-polymerase chain reaction (RT-PCR). The levels of IL-1 alpha and IL-6 mRNA induced by mineral fiber exposure were greatest in AMs exposed to TW, crocidolite, chrysotile and RF1 in that order. However, both gene expression of iNOS and TNF alpha were not elevated in both crocidolite and TW exposure, despite their high pathological potential. These data suggested that IL-1 alpha and IL-6 may be useful indicators for the risk assessment of MMMFs.

[A case of pulmonary fibrosis with many asbestos bodies in bronchoalveolar lavage fluid after exposure to asbestos and man-made mineral fibers].

We report a case of severe pulmonary fibrosis in a patient exposed to asbestos and other natural and man-made mineral fibers (MMMF) over a period of time. A 63-year-old man was admitted to our hospital because of progressive dyspnea and severe hypoxemia with hypercapnea. Mineral fibers recovered by bronchoalveolar lavage were analyzed by scanning electron microscope (SEM) and energy-dispersive x-ray spectroscopy (SEM-EDS). The bronchoalveolar lavage fluid (BALF) included a large number of asbestos bodies (116,000/ml). The cores of the asbestos fibers were crocidolite, and no vitreous fibers nor other kinds of man-made mineral fibers (MMMFs) were identified. To our knowledge, the number of asbestos bodies per ml of this patient's BALF is the greatest ever reported. Insufficient personal protection of the airways, high concentrations of inhaled fibers, co-exposure to cigarette smoke, and prolonged biopersistence of crocidolite asbestos fibers are presumed to be the causes of such severe asbestosis.

[Pulmonary involvement in acute febrile neutrophilic dermatosis (Sweet's syndrome)].

We encountered a 55-year-old man with pulmonary involvement in acute febrile neutrophilic dermatosis (Sweet's syndrome). He had been treated with steroids for Sweet's syndrome for 2 years, and on September 17, 1998 presented with a cough and a fever of 38.9 degrees C. Physical examination revealed fine crackles at the bases of both lungs. Chest radiography and computed tomography demonstrated reticular and nodular infiltrates in both lungs. Treatment with a variety of antibiotic agents and an antifungal agent was not effective. Sputum culture was sterile and bronchial washings were negative for infectious pathogens. Transbronchial biopsy revealed a mild chronic interstitial infiltrate and an inflammatory exudate in bronchiolo-alveolar tissue. The pulmonary lesions and cutaneous lesions were resolved by intradermal injections of triamcinolone acetonide in addition to oral prednisolone. Although the apparent neutrophilic infiltrates cited by earlier reports were not observed in transbronchial biopsy specimens, the clinical course in this case suggested that our patient had Sweet's syndrome with pulmonary involvement.