Giant cell carcinoma causing rapidly progressive respiratory failure as the presenting feature of AIDS.

The incidence of lung cancer has been increasing among HIV-positive patients. The majority of these cases were in patients previously diagnosed as HIV-positive and treated with highly active antiretroviral therapy (HAART). Here, we report a 56-year-old male patient with lung cancer, who was diagnosed as HIV-positive after the onset of neck pain and lumbago and thus, was not treated with anti-AIDS therapy. The patient developed rapidly progressive and fatal respiratory failure. Autopsy demonstrated giant cell carcinoma of the lung responsible for carcinomatous lymphangitis. This case highlighted the possibility that pulmonary carcinogenesis in HIV-positive patients is not necessarily associated with HAART therapy.

Lung cancer in chronic hypersensitivity pneumonitis.

BACKGROUND: So far, the association of lung cancer with chronic hypersensitivity pneumonitis (CHP) has not been studied. OBJECTIVE: We examined the prevalence and revealed clinical features of lung cancer in CHP. METHODS: We retrospectively reviewed the medical records from 1994 through 2005 and identified 11 patients (15 lesions) with lung cancer among 104 patients with CHP. Their clinical features and histopathological findings were analyzed. RESULTS: Ten men and 1 woman with a median age of 68.9 years were included. All patients had a smoking history. The most prevalent histopathological type of lung cancer was squamous cell carcinoma (53%), and all tumors were located in the peripheral region of the lung. Four patients suffered from lung cancer after the diagnosis of CHP and 1 patient had lung cancer before the diagnosis of CHP. The histological pattern of CHP showed a predominantly usual interstitial pneumonia-like lesion. Tumors were located adjacent to honeycombing in 7 (47%) of 15 lesions, bullae in 4 (27%) lesions, and relatively normal lung in 4 lesions. CONCLUSIONS: Since the prevalence of lung cancer in CHP seems to be high (10.6%) as seen in idiopathic pulmonary fibrosis, physicians should be aware of the possible complication of lung cancer in CHP.

A phase I study of TS-1 plus carboplatin in patients with advanced non-small-cell lung cancer.

TS-1 is a novel oral anticancer agent comprised of tegafur, a prodrug of 5- flurouracil, and two modulators. A phase i study of tS-1 plus carboplatin combination therapy was conducted to determine the maximum tolerated dose (MTD), recommended dose (RD), and dose limiting toxicities (DLT) in advanced non-small-cell lung cancer (NSClC). TS-1 was given orally at a dose of 80 mg/m(2)/day for 2 weeks, followed by a 2-week rest. Carboplatin was given intravenously on day 8 at a dose of 4.0, 5.0, 6.0 area under the curve (AUC) values. Fifteen patients with advanced NSClC were analyzed. the grade 3-4 toxicities observed during the first cycle were febrile neutropenia (6%), anemia (6%), anorexia (6%), and diarrhea (6%). these toxicities were reversible and manageable. The MTD for carboplatin was evaluated to be more than 6.0 AUC values, as one of six patients developed Dlt at this dose. the RD for carboplatin was estimated as 6.0 AUC values. Objective responses were seen in five patients (response rate 33%).

Pathogenesis of cBFL in common with IPF? Correlation of IP-10/TARC ratio with histological patterns.

BACKGROUND: A Th1 predominant immune response has been shown in acute hypersensitivity pneumonitis. Predominance of Th2 appears to favour the development of pulmonary fibrosis through the profibrotic process and has been described as crucial in the progression of idiopathic pulmonary fibrosis. Chronic bird fancier's lung (cBFL) can present with a histological pattern of usual interstitial pneumonia (UIP)-like lesions. Little is known about the Th1/Th2 balance in the pathogenesis of cBFL. METHODS: To evaluate the relevance of Th1-type chemokines (interferon-inducible protein, IP-10) and Th2-type chemokines (thymus- and activation-regulated chemokine, TARC) and their receptors (CXCR3 and CCR4) to the histological patterns of cBFL, 40 patients with cBFL who underwent surgical lung biopsies, 12 with acute BFL (aBFL) and 10 healthy volunteers were analysed. IP-10 and TARC levels in serum and bronchoalveolar lavage (BAL) fluid were measured by ELISA. Immunohistochemistry for CXCR3 and CCR4 was performed on surgical lung specimens. RESULTS: The ratio of TARC to IP-10 in the serum of patients with UIP-like lesions was significantly higher than in patients with cNSIP/OP-like lesions, aBFL and healthy volunteers. The ratio of CCR4 to CXCR3 in patients with UIP-like lesions was significantly higher than in those with cNSIP/OP-like lesions and fNSIP-like lesions. The ratio of CCR4-positive to CXCR3-positive cells correlated with the ratio of TARC to IP-10 in serum. CONCLUSIONS: A Th2 predominant immune response may play an important role in the development of UIP-like lesions, as already observed in idiopathic pulmonary fibrosis. A Th1 predominance may play a role in the development of cNSIP/OP-like lesions in cBFL.

Chronic bird fancier's lung: histopathological and clinical correlation. An application of the 2002 ATS/ERS consensus classification of the idiopathic interstitial pneumonias.

BACKGROUND: Chronic bird fancier's lung (BFL) has often been misdiagnosed as one of the idiopathic interstitial pneumonias (IIPs). METHODS: To define the clinical and pathological characteristics of chronic BFL, 26 patients with chronic BFL from whom a surgical lung biopsy specimen was taken between October 1992 and June 2001 were evaluated. The histopathological characteristics of the surgical lung biopsy specimens were examined and correlations between the histopathology and clinical characteristics were analysed. The quality of chronic inflammatory and fibrotic changes was expressed according to the 2002 ATS/ERS consensus classification of IIPs. RESULTS: Two patients were diagnosed as having bronchiolitis obliterans organising pneumonia (BOOP)-like lesions, five as having cellular non-specific interstitial pneumonia (NSIP)-like lesions, and eight as having fibrotic NSIP-like lesions. The other 11 patients were considered to have usual interstitial pneumonia (UIP)-like lesions because of the temporal heterogeneous appearances of the fibrotic changes. However, fibrosis in these patients had developed in centrilobular as well as perilobular areas, suggestive of hypersensitivity pneumonitis. Nineteen patients (73.1%) had multinucleated giant cells, often with cholesterol clefts, while only five patients (19.2%) had granulomas. Patients with BOOP-like or cellular NSIP-like lesions tended to have recurrent acute episodes, whereas patients with UIP-like lesions had an insidious onset. Patients with BOOP-like or cellular NSIP-like lesions had a more favourable outcome than those with fibrotic NSIP-like and UIP-like lesions. CONCLUSIONS: The qualities of chronic inflammatory and fibrotic lesions vary significantly among patients with chronic BFL but correlate with clinical features and prognosis.

[A case of Churg-Strauss syndrome in which positive rheumatoid factor and MPO-ANCA preceded the development of clinical symptoms of vasculitis].

A 52-year-old man in whom bronchial asthma had been diagnosed in 1995 was admitted for the treatment of Churg-Strauss syndrome in June 1997. Positive tests MPO-ANCA and rheumatoid factor preceded the symptoms of vasculitis for several months. A skin biopsy revealed infiltration of eosinophils in the vessel walls, and the diagnosis of Churg-Strauss syndrome was confirmed. After systemic administration of corticosteroids, the symptoms other than mononeuritis improved markedly, and his MPO-ANCA and rheumatoid factor became negative. Rheumatoid factor and MPO-ANCA may be useful for the early diagnosis of Churg-Strauss syndrome in patients with bronchial asthma in which a well-controlled disease develops into an intractable condition.

Calretinin promoter for suicide gene expression in malignant mesothelioma.

To achieve specific and efficient expression of transfected suicide gene in malignant mesothelioma cells, we explored the 5-flanking region (2.2 kb) of the calretinin gene as a tumor-specific promoter. RT-PCR analysis demonstrated the expression of calretinin mRNA in two human malignant mesothelioma cell lines (H2052 and 211 H). A reporting vector containing the calretinin promoter (pCAL-LUC) exhibited relatively high luciferase activity in these cell lines. After transfecting an expression vector containing the calretinin promoter-bound thymidine kinase gene (pCAL-TK) into the cells, we examined their sensitivity to ganciclovir (GCV). In the mesothelioma cell lines, the pCAL-TK transfected cells became about 100 times more sensitive to GCV than the parental cells. The calretinin promoter seems to be a promising candidate as a specific and efficient promoter in malignant mesothelioma.

Neuron specific enolase promoter for suicide gene therapy in small cell lung carcinoma.

To investigate the specific transduction of a suicide gene into human small cell lung carcinoma (SCLC) cells, we explored the promoter region of the neuron specific enolase (NSE) gene as a tumor-specific promoter. In Northern blot analysis, NSE mRNA was expressed more abundantly in the SBC3 human SCLC cell line than in the RERF human SCLC cell line, the A549 human lung adenocarcinoma cell line and the HeLa human uterine cervix epitheloid carcinoma cell line. A reporting vector containing the NSE promoter (pNSE-LUC) exhibited higher luciferase activity in SBC3 than in the other three cell lines. After transfecting an expression vector containing the NSE promoter-bound HSV-TK gene (pNSE-TK) into the cells, we measured their sensitivity to ganciclovir (GCV). In SBC3, pNSE-TK transfected cells showed about the same sensitivity to GCV as non-transfected (parental) cells. Though the NSE promoter itself is not optimal for use in suicide gene transfer to SCLC cells, it might be applied as a tumor-specific promoter after enhancement of its activity.

Adenovirus-mediated suicide gene transfer to small cell lung carcinoma using a tumor-specific promoter.

The gastrin-releasing peptide (GRP) is expressed in most types of small cell lung carcinoma (SCLC) and the GRP promoter is thought to be potentially useful for tumor-specific expression of the suicide gene in SCLC. We constructed an adenovirus containing the herpes simplex thymidine kinase suicide gene driven by the GRP promoter (AdGRP-TK) and transfected it into GRP-expressing SCLC cells (SBC5) to confer sensitivity to ganciclovir (GCV). After infection with AdGRP-TK, SBC5 cells became more sensitive to GCV in vitro. In nude mice, a subcutaneously-inoculated tumor of SBC5 cells infected with AdGRP-TK in advance regressed completely after intraperitoneal administration of GCV. These results suggest that adenovirus-mediated gene transfer of the suicide gene followed by pro-drug treatment may be applicable to SCLC.

Progesterone induces apoptosis in malignant mesothelioma cells.

Progesterone has been used in the treatment of patients with recurrent or metastatic progesterone receptor-positive endometrial carcinoma and breast cancer. In vitro study using a breast cancer cell line, T47D, demonstrated an increase in p53 gene expression and induction of apoptosis by the administration of progesterone. Therefore, we investigated the effect of progesterone administration on the proliferation and apoptosis in a mesothelioma cell line, 211H. The expression of the progesterone receptor gene was detected in this cell line by a nested RT-PCR method. The proliferation of the cell line was suppressed after a 10-day incubation with 30 microM progesterone. In progesterone-treated 211H cells, apoptotic cells were detected by TUNEL assay and nuclear DNA fragmentation analysis. These results clearly demonstrated that progesterone administration suppressed the cell proliferation and induced apoptosis in malignant mesothelioma cells.

Inhalation provocation tests in chronic bird fancier's lung.

BACKGROUND: Patients with chronic bird fancier's lung (BFL) can be classified into two types. One group of patients develops chronic disease with fluctuating acute episodes, including low-grade fever, mild exertional dyspnea, and cough (fluctuating chronic BFL; formerly termed recurrent and relapsing chronic BFL). The other group of patients shows no history of acute episodes (insidious chronic BFL). The diagnosis of chronic BFL is difficult, since the onset of chronic BFL may be insidious, with few if any symptoms during the early stages of the disease process. STUDY OBJECTIVE: To attempt to diagnose the conditions of these patients more precisely, inhalation provocation tests were conducted using avian dropping extracts. DESIGN: Retrospective chart review. SETTING: The Tokyo Medical and Dental University Hospital in Japan. PATIENTS: Eleven patients with chronic BFL (6 with fluctuating chronic BFL and 5 with insidious chronic BFL) and 6 control subjects (4 asymptomatic bird owners and 2 idiopathic pulmonary fibrosis patients) were evaluated. MEASUREMENTS AND RESULTS: Inhalation provocation tests using avian dropping extracts were conducted. All BFL patients were evaluated as positive or probable by inhalation challenge, whereas control subjects were evaluated as negative. A peripheral leukocytosis, an increase of alveolar-arterial oxygen pressure difference, an increase of body temperature, and the development of respiratory symptoms including cough and dyspnea were more frequently observed in chronic BFL patients than in control subjects. All the BFL patients had an increase in neutrophils in BAL fluids following inhalation challenge. CONCLUSIONS: We validated the utility of inhalation challenge for the diagnosis of chronic BFL, including fluctuating and insidious BFL. We also demonstrated that neutrophilia in BAL fluids following inhalation challenge could be added to the diagnostic criteria for chronic BFL.

Relationship between apoptosis and immunohistochemical staining for proliferating cell nuclear antigen and Ki-67 in non-small cell lung cancer.

The relationship between apoptosis and cellular proliferative activity in human non-small cell lung cancer (25 cases) was investigated using the in situ DNA nick-end labeling method and immunohistochemistry for both proliferating cell nuclear antigen (PCNA) and Ki-67 antigen. Comparison of the distribution of Ki-67-positive cells to that of apoptotic cells shows an inverse correlation in semi-serial sections. The PCNA labeling rates were closely correlated with Ki-67 labeling rates in non-small cell lung cancer. It was concluded that the immunostainings of PCNA and Ki-67 were almost equally valuable for assessing the proliferative activity in paraffin-embedded tissue from non-small cell lung cancer and that apoptosis may be related with the cell cycle in this cancer.

Use of gastrin-releasing peptide promoter for specific expression of thymidine kinase gene in small-cell lung carcinoma cells.

For specific transduction of herpes simplex virus thymidine kinase (HSV-tk) into human small-cell lung carcinoma (SCLC) cells, we explored the 5'-flanking region (-1.1 kb) of the gastrin-releasing peptide (GRP) gene as a lung cancer-specific promoter. RT-PCR analysis demonstrated expression of GRP mRNA in the SBC5 human SCLC cell line but not in the RERF human SCLC cell line, the A549 human lung adenocarcinoma cell line or the HeLa human uterine cervix epithelioid carcinoma cell line. A reporting vector containing the GRP promoter (pGL2-GRP) exhibited higher luciferase activity in SBC5 than in the other 3 cell lines. After transfecting an expression vector containing the GRP promoter-bound HSV-tk gene (pGRP-TK) into the cells, we measured their sensitivity to ganciclovir (GCV). In SBC5, pGRP-tk-transfected cells became about 100 times more sensitive to GCV than parental cells in vitro. In nude mice, tumors of pGRP-tk-transfected SBC5 regressed completely after i.p. administration of GCV. GRP promoter might be a good tool for tumor-specific transduction of suicide genes in GRP-expressing SCLC cells.

Mediastinal fibromatosis presenting with superior vena cava syndrome.

We encountered a fatal case of mediastinal fibromatosis in a 67-year-old female in whom there was aggressive infiltration into the large vessels, nerves and pericardium. She presented with the superior vena cava syndrome, Horner's syndrome, paralysis of bilateral vocal cords and diaphragm and heart failure. Mediastinoscopical examination revealed an extremely firm tumor adhering to the sternum, trachea and brachiocephalic artery. She died of severe heart failure due to the disturbed dilatation of the heart and ventilatory insufficiency. Although mediastinal fibromatosis is very uncommon and sometimes difficult to diagnose at an early stage, physicians should be aware of this disease for the differential diagnosis of mediastinal tumors.

Hypersensitivity pneumonitis among workers cultivating Tricholoma conglobatum (shimeji).

We report five cases of hypersensitivity pneumonitis among workers cultivating Tricholoma conglobatum (shimeji). After having worked for 5 to 20 years, they began to notice symptoms of cough, sputum, and dyspnea. They were diagnosed as having a hypersensitivity pneumonitis based on clinical features, bronchoalveolar lavage and transbronchial lung biopsy. By the double immunodiffusion test, precipitating lines between shimeji spore antigen and sera were observed in all of the patients. By enzyme-linked immunosorbent assay, the antibody activities against shimeji and three species of fungi (Cladosporium sphaerospermum, Penicillium frequentans, and Scopulariopsis species) were significantly higher in the sera of the patients than in those of normal subjects who were cultivating shimeji. Although it is not clear what causes this disease, these findings may be helpful in determining the specific antigen.

Cloning and functional expression of human aquaporin8 cDNA and analysis of its gene.

The cDNA and the gene of human aquaporin8 (AQP8) were cloned from human testis cDNA and a genomic library, respectively. The AQP8 cDNA encodes 261 amino acids. The identity of the amino acid sequence to other aquaporins is highest with a plant water channel, gamma-TIP (40.4%), while AQP2 and AQP3 are 28.9 and 29.5% identical to human AQP8, respectively. The human AQP8 is only 74.9% identical to rat AQP8 and 76.0% identical to mouse AQP8. In Northern blot analysis, approximately 1.35-kb human AQP8 mRNA was expressed in pancreas and colon, but not in other tissues. Absence of human AQP8 in testis is noteworthy as rat AQP8 was abundantly expressed in testis. The expression of human AQP8 cRNA in Xenopus oocytes increased osmotic water permeability by 10-fold. AQP8 was not permeable to urea nor to glycerol. The AQP8 gene has five introns, and the locations of exon-intron boundaries were different from those of the other mammalian aquaporins, suggesting its separate phylogenetic origin.

Acute lung injury after inhalation of water-proofing spray while smoking a cigarette.

A 34-year-old Japanese woman developed acute lung injury soon after inhaling a water-proofing spray which she applied onto her ski suit while smoking a cigarette at the same time. She initially demonstrated arterial hypoxemia (PaO2 = 59 mm Hg) and ground-glass opacities in both lung fields on the CT scan, which both returned to normal without any medication. Several water-proofing sprays, which are easily obtainable in Japan, contain 1,1,1-trichloroethane, liquefied petroleum gas and fluoride resin. Although these components have not been reported to be toxic to the lung yet, high concentrations of these components and/or the pyrolytic products of fluoride resin may have caused acute lung injury in this case.