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Biomedical subjects

Takumi Kishimoto

Publications and source records attributed to Takumi Kishimoto.

At least 19 recordsLinked to original sources

Heterogeneous nuclear ribonucleoprotein B1 expression in malignant mesothelioma.

Heterogeneous nuclear ribonucleoprotein B1, an RNA-binding protein required for mRNA maturation, reportedly is overexpressed in early lung cancer and in several other tumors, including precancerous lesions. Expression of the protein was assessed immunohistochemically in 39 specimens of malignant mesothelioma and five of non-neoplastic pleura, and by flow cytometry in a human epithelioid mesothelioma cell line. No tumor showed overexpression, but 29 of 39 cases showed modest expression. Patients whose tumors showed expression had significantly better survival rates than others. Epithelioid tumors and reactive mesothelial cells were more likely to express the protein than sarcomatoid tumors and resting mesothelial cells. Flow cytometric analysis of an epithelioid mesothelioma cell line demonstrated stronger expression in exponentially growing than growth-restricted cells. Heterogeneous nuclear ribonucleoprotein B1 is expressed widely in malignant mesotheliomas and in reactive mesothelial cells, but is not overexpressed. This protein may regulate proliferation linked with differentiation toward epithelioid morphology in mesothelial cells. Expression of the protein may be a prognostic indicator for patents with malignant mesothelioma.

Adult↗

Involvement of IL-10 and Bcl-2 in resistance against an asbestos-induced apoptosis of T cells.

To analyze the possibility that immunological alteration in asbestos-related diseases (ARDs) such as asbestosis (ASB) and malignant mesothelioma (MM) may affect the progression of cancers, a human adult T cell leukemia virus-immortalized T cell line (MT-2Org) was continuously exposed to 10 mug/ml of chrysotile-B (CB), an asbestos. After at least 8 months of exposure, the rate of apoptosis in the cells became very low and the resultant subline was designated MT-2Rst. The MT-2Rst cells were characterized by (i) enhanced expression of bcl-2, with regain of apoptosis-sensitivity by reduction of bcl-2 by siRNA, (ii) excess IL-10 secretion and expression, and (iii) activation of STAT3 that was inhibited by PP2, a specific inhibitor of Src family kinases. These results suggested that the contact between cells and asbestos may affect the human immune system and trigger a cascade of biological events such as activation of Src family kinases, enhancement of IL-10 expression, STAT3 activation and Bcl-2 overexpression. This speculation was partially confirmed by the detection of elevated bcl-2 expression levels in CD4 + peripheral blood T cells from patients with MM compared with those from patients with ASB or healthy donors. Further studies will be required to verify the role of T cells with enhanced bcl-2 expression in tumor progression induced by asbestos exposure.

Apoptosis↗

Infrequent existence of simian virus 40 large T antigen DNA in malignant mesothelioma in Japan.

Malignant mesothelioma is the most common primary pleural neoplasm. Association of simian virus 40 (SV40) with malignant mesothelioma has been reported, suggesting that SV40 plays an important role in the origin of a subset of these tumors. However, significant geographic variation is present as to how often this association occurs. As no study concerning SV40 in malignant mesothelioma has been reported from Japan, we examined the frequency of SV40 infection in Japanese malignant mesothelioma cases. In pleural malignant mesothelioma tissue from 35 patients in Japan, we sought the presence of SV40 large T antigen DNA using real-time polymerase chain reaction (PCR), as well as expression of the viral protein using immunohistological methods. Real-time PCR demonstrated that two of 35 mesotheliomas contained DNA sequences encoding portions of SV40 large T antigen. None of the 35 malignant mesothelioma specimens showed immunoreactivity for SV40 large T antigen. SV40 infection does not appear to have a major role in the development of malignant mesothelioma in Japan.

Adult↗

Alterations of Fas and Fas-related molecules in patients with silicosis.

Persons with silicosis have not only respiratory disorders but also autoimmune diseases. To clarify the mechanisms involved in the dysregulation of autoimmunity found in patients with silicosis, we have been focusing on Fas and Fas-related molecules in the Fas-mediated apoptotic pathway, because Fas is one of the most important molecules regulating auto-immunity involving T cells. Our findings showed that patients with silicosis exhibited elevated serum soluble Fas levels, an increased relative expression of the soluble fas and dcr3 genes in peripheral blood mononuclear cells, high levels of other variant messages of the fas transcript, relatively decreased expression of genes encoding several physiological inhibitors (such as survivin and toso), and dominancy of lower-membrane Fas expressers in lymphocytes, which transcribe soluble fas dominantly, compared with soluble fas transcription in healthy donors. These findings are consistent with known features regarding immunological factors, such as serum immunogulobulin G levels and the titer of anti-nuclear autoantibodies in silicosis. In addition, anti-caspase 8 autoantibody and anti-Fas autoantibody were detected in serum specimens from patients with silicosis, and a functional assay showed that anti-Fas antibody stimulated Fas-mediated apoptosis. We hypothesize that there are two subpopulations of silicosis lymphocytes. One is a long-term surviving fraction that includes self-recognizing clones showing lower levels of membrane Fas and inhibition of Fas/Fas ligand binding in extracellular spaces. The other subpopulation exhibits apoptosis caused by silica and silicates, is recruited from bone marrow, shows higher levels of membrane Fas, and is sensitive to anti-Fas autoantibody. Further investigation should be performed to confirm the effects of silica and silicates on the human immune system.

Autoantibodies↗

Lung disorders of workers exposed to rush smear dust in China.

The aim of this study was to evaluate the lung disorders of the workers exposed to rush smear dust. A cross sectional study was carried out on 1,709 current workers (788 male, 921 female) in 80 factories. All subjects were asked by questionnaire, and health examination including chest X-ray was conducted for 661 workers in 35 factories. Lung function test was also examined for 119 non-smoking males among 661 subjects. Dust samplings were collected and total and respirable dust concentrations at 127 spots in 35 factories were measured. The geometric mean dust concentration in the workshops was up to 20.00 mg/m(3), and the geometric mean respirable dust concentration reached 8.22 mg/m(3). The mean quartz concentration of accumulated dust was 29.2%. The prevalence of radiographic small opacities profusion category > or = 1/0, according to the ILO 1980 Classification System, was 2.6% among 661 employees. One worker was found to have pneumoconiotic findings of 2/2 profusion accompanied with large opacity. The prevalence of pneumoconiosis (1/0 or more) correlated with cumulative dust exposure (r=0.192, p<0.0001). The similar relationship was found between the prevalence rate of cough or sputa and worksite dust concentration. In non-smokers, a positive association was found between the prevalence of cough and occupational exposure duration (r=0.080, p=0.004). Approximately 19.3% and 34.5% of employees suffered from respiratory impairment for FVC and FEV1.0, respectively. This is the first report of "rush" pneumoconiosis in China. Rush mat workers were found to be at high risk for pneumoconiosis, a preventable disease. Our results showed a dose-response relationship between rush-mat dust level and the prevalence of pneumoconiosis. Similar relationship between the prevalence of cough and sputum and the work duration was found for non-smoking workers but not for smoking workers.

Adult↗

Clinical significance of the expression of tumor-associated antigen, RCAS1, and its soluble protein in pleural fluid in malignant mesothelioma.

RCAS1 is a type II membrane protein which is also secreted as a soluble protein. RCAS1 may play a role in evading immune surveillance by tumor cells and be responsible for the aggressive behavior of tumors. We examined the usefulness of RCAS1 in the follow-up of malignant mesothelioma. In addition, we examined the usefulness of its soluble protein (sRCAS1) in pleural effusion for the diagnosis of malignant mesothelioma. We studied 38 patients with pleural malignant mesothelioma and examined the correlation between RCAS1 expression, clinicopathologic variables and overall survival. We also determined the pleural fluid sRCAS1 concentration with an enzyme-linked immunosorbent assay (ELISA). We found that 34 out of 38 (89.5%) malignant mesothelioma cells stained for RCAS1. The positive rate was 90.9% in biphasic type, 78.6% in epithelioid type, and 100% in sarcomatoid type. No statistically significant correlation was observed between RCAS1 expression and gender, age, histology or clinical stage. Interestingly, survival of the malignant mesothelioma patients with RCAS1 expression was significantly increased compared with those without (median survival time: 13.0 vs. 4.3 months, p=0.011). Multivariate analysis of prognostic factors, using the Cox proportional hazards model, revealed that RCAS1 expression had a significantly positive effect on survival. sRCAS1 concentrations in pleural fluid in malignant mesothelioma were lower than those in lung cancer (2.18+/-2.20 vs. 46.3+/-129 U/ml; p=0.019). RCAS1 expression is informative for the follow-up of malignant mesothelioma patients. In addition, sRCAS1 in pleural fluid may be useful for the diagnosis of malignant mesothelioma.

Adult↗

Nonparaneoplastic limbic encephalitis with relapsing polychondritis.

Relapsing polychondritis (RP), which shows pain, swelling and destruction of the affected parts, is a rare autoimmune disorder affecting cartilage. We report a patient with RP that affected skull cartilage, who subsequently developed multifocal meningoencephalitis. The patient presented with severe recent memory disturbance, anxiety and moderate depression. MRI study showed bilateral median temporal lobe lesions including hippocampi and amygdaloidal bodies, abnormal findings that disappeared after treatment with high-dose steroids. This is thought to be the first case of RP presenting amnesic syndrome and mental disorder associated with nonparaneoplastic limbic encephalitis involving bilateral hippocampi and amygdaloidal bodies detected by MRI.

Anxiety↗

Clinical features of eleven cases of Mycobacterium avium-intracellulare complex pulmonary disease associated with pneumoconiosis.

The relationship between silicosis and tuberculosis is well known. Also other mycobacteria such as Mycobacterium kansasii often occur in association with pneumoconiosis. However, there are few reports describing an association of M. avium-intracellulare complex (MAC) lung disease and pneumoconiosis. The purpose of the present study is to describe clinical features of MAC respiratory infection associated with pneumoconiosis. Eleven patients with MAC respiratory infection associated with pneumoconiosis (all men, 6 with silicosis and 5 with welders' pneumoconiosis) were collected. A determination of whether or not MAC caused pulmonary disease was made using the 1997 criteria required by the American Thoracic Society. Radiologically, cavity formation as well as upper lung field predominance of MAC disease were observed in 8 of 11 cases (72.7%). Two of 11 patients died of respiratory failure. Our present study clearly demonstrates that clinical features of MAC respiratory infection associated with pneumoconiosis were different from MAC without underlying diseases.

Aged↗

Evaluation of the efficiency of respiratory protective equipment based on the biological monitoring of styrene in fibreglass reinforced plastics industries.

The purpose of the present study was to determine the efficiency of respiratory protective equipment in a fibreglass reinforced plastic factory by comparing results of environmental and biological monitoring of exposure to styrene. Five factories including 39 workers were investigated. Three types of respiratory protective equipment were tested: one was a half-mask air-purifying respirator equipped with a cartridge for organic solvents, another was a disposable gauze respirator impregnated with charcoal filter, and the third was a dust-proof respirator. The frequency of cartridge exchange of a half-mask respirator was twice a day only at one factory, and that was less than once a month at other factories. The site concentrations exceeded 20 ppm at 10 of the 82 sampling points (12.2%), and 22 of the 39 workers' (56.4%) personal exposure exceeded 20 ppm which is the current occupational exposure limit recommended by the Japan Society for Occupational Health. The efficiency of disposable gauze respirators and dust-proof respirators was low or rather zero. The average efficiency of half-mask respirators in which cartridges were exchanged twice a day and once a month was 83.6% and 46.6%, respectively. There was a significant disparity in the efficiency of the respirator depending on the frequency of cartridge exchange (p<0.05). Overall this study showed that even though a half-mask respirator is used and its cartridge is exchanged every half a day, workers exposed to a styrene concentration at or over 122 ppm are expected to inhale more than 20 ppm of styrene.

Adult↗

Mycobacterium kansasii osteomyelitis in a patient with AIDS on highly active antiretroviral therapy.

Skeletal infections with atypical mycobacteria are usually a manifestation of advanced HIV disease with most patients having CD4 counts of less than 100 cells/mm3. We report a case of Mycobacterium kansasii vertebral osteomyelitis on highly active antiretroviral therapy with a CD4 count of 320 cells/mm3 and viral load below the level of detection at the onset.

Acquired Immunodeficiency Syndrome↗

Malignant pleural mesothelioma in parts of Japan in relationship to asbestos exposure.

Malignant pleural mesothelioma is induced by asbestos exposure. Many reports have described this situation in America and European countries, but a few have been published in Japan. In this study malignant pleural mesothelioma cases in hospitals located in an area facing the Seto Inland Sea were evaluated. A total of 106 patients were examined with 100 patients having had occupational exposure to asbestos and 6 patients without such histories of asbestos exposure. Ninety seven were male and 9 were female. Ages ranged from 41 to 87 yr with mean of 64.8+/-5.3 yr. Thirty seven cases showed epithelial type of tumor, 25 biphasic type and 15 showed sarcomatous. The remaining 23 cases had insufficient evidence for typing the tumor. The mean survival rate for all cases was 9.2+/-11.6 months. Fifty-one patients had occupational histories of shipyard work, 16 patients worked in asbestos cement piping, and the remainder were employed in miscellaneous jobs related asbestos exposure. The duration of asbestos exposure ranged up to 20 yr or longer with the mean of 17.2+/-8.9 yr and the average latent period for the occurrence of malignant pleural mesothelioma was more than 31 yr with the mean of 37.0+/-13.3 yr. Quantification of asbestos bodies in the lungs indicated a high concentration in most patients and the major types of asbestos fibers were crocidolite and amosite. Six cases appeared after exposure to chrysotile. These results indicated that ninety four percent of malignant pleural mesothelioma appeared due to the exposure to asbestos including crocidolite and amosite. The remainder may be blamed on exposure to chrysotile.

Adult↗

[A case of splenic hemorrhage in the course of malignant mesothelioma].

A 56-year-old man was admitted to our hospital because of mass lesions at the levels of the right upper and lower lung regions on a chest plain radiograph. Chest computed tomography showed tumors which projected from the pleura of the right upper and lower lung fields. One particular point of interest was the complete separation of the tumors from each other. Malignant mesothelioma was diagnosed by biopsy of the pleura via echogram. Both chemotherapy and radiotherapy were administered because of brain metastasis and direct rib invasion. Under this combined therapy, sudden anemia and hypotension appeared due to splenic hemorrhage, which suggested splenic metastasis of the malignant mesothelioma. Multiple metastases in, for example, the spleen, brain, lung, liver, duodenum, small intestine, kidney, adrenal gland, vertebra, thyroid gland, and lymph nodes were confirmed by autopsy. Distant metastasis is rare for malignant mesothelioma, and we report here a case of splenic metastasis with splenic hemorrhage in malignant mesothelioma.

Brain Neoplasms↗

Clinical study of asbestos-related lung cancer.

We analyzed the characteristics of 120 patients of primary lung cancer supposed to be induced by exposure to asbestos. Most of 120 patients were male and the age ranged from 47 to 87 years with a median of 70 years. No particular tendency was observed in the histological types of the lung cancer in 120 patients. Forty of the 120 patients were heavy smokers. When the occupational history was analyzed, most of the patients had been exposed to asbestos in former Japanese naval shipyard, commercial shipyards, construction industry and ironworks. The term of asbestos exposure was 2 to 60 years with a median 27 years. Lung cancers appeared after 15 to 69 years with a median 43 years from the initial exposure to asbestos. Lung cancer was accompanied by asbestosis in 35 patients and by pleural plaques in 77. Twenty-two patients had both asbestosis and pleural plaques. The number of asbestos bodies per 5 g wet lung tissue for 72 patients whose lung tissues obtained from autopsy or surgery was more than 150 bodies which meant the number of occupational asbestos exposure. As for the kinds of asbestos fibers of 32 patients, 14 patients exposed to crocidolite, 10 patients to amosite and 8 patients to chrysotile.

Age of Onset↗

[A case of triple malignancies (gastric cancer, lung cancer and malignant pleural mesothelioma) after asbestos exposure].

This case study centers on a seventy-eight-year-old man with triple malignancies, namely, gastric cancer, lung cancer and malignant pleural mesothelioma, all of which developed at different times. The histological types were adenocarcinoma of the stomach, squamous cell carcinoma of the lung and sarcomatous malignant pleural mesothelioma. Gastric cancer was treated by endoscopic mucosal resection 2 years ago. The patient presented with a chief complaint of dyspnea, and right pleural effusion was found on chest radiography. The right-side effusion disappeared spontaneously, but a small mass on the left side was diagnosed as lung cancer, and so left inferior lobe resection was performed. Malignant pleural mesothelioma appeared after one year of pleural effusion and the patient died of mesothelioma one year after diagnosis. At autopsy, the gastric cancer and lung cancer had not relapsed and malignant pleural mesothelioma had metastasized to the lung, liver, adrenal gland and small intestine. He was a sailor by profession and it was obvious that he had been exposed to asbestos, because 538 asbestos bodies per 5 g of wet lung tissue were detected. His advanced age was one of the risk factors for the multiple malignancies, and the asbestos exposure was considered to have compounded these hazards to cause the triple malignancies. It is well known that lung cancer and malignant mesothelioma are induced by asbestos exposure, but multiple cancers including lung cancer and malignant mesothelioma are extremely rare.

Adenocarcinoma↗

The current state of workers' pneumoconiosis in relationship to dusty working environments in Okayama Prefecture, Japan.

This study involved the examination of 1,006 chest x-ray films of workers from the industries devoted to shipyard welding, stone grinding, and refractory crushing in southern Okayama prefecture. Of the reviewed films, analysis was focused on subjects with a profusion rate of 0/1 as well as pneumoconiotic subjects (exhibiting profusion rates of 1/0 or greater) in order to discover cases in the beginning stages. One-hundred-and-seventy-four films illustrated a profusion rate of 0/1 or greater, and the proportion of this profusion rate was revealed to be highest in shipyard welders. Even some workers under 40 years of age were found to have already developed pneumoconiosis. Of these 1,006 subjects, 30 volunteers permitted us to measure their personal dust exposure concentrations. The measured concentration of the shipyard welders' dust exposure (respirable dust; 3.3 86.3 mg/m3, total dust; 7.5-117.0 mg/m3) was higher than those of the other 2 industries. Statistical differences among the industries were observed in the respirable dust concentrations. A statistically significant positive correlation was demonstrated between the working duration in dusty environments and the rate of profusion. The present findings suggest the need for taking adequate measures in Okayama in order to prevent workers from developing, or to help retard the progression of, pneumoconiosis.

Adult↗

[Clinical evaluation of rounded atelectasis induced by exposure to asbestos].

We encountered 15 patients with rounded atelectasis induced by exposure to asbestos from 1992 to 1999. All patients were men whose ages ranged from 42 to 85 years, with a mean age of 64.2 +/- 11.5 years. Rounded atelectasis was present only in the right lung and two patients had 2 rounded atelectasis in the right lung. In eight cases, the rounded atelectasis was found in segment 10, while in the others, it was found in segments 4, 5, 6, 8, and 9. Although evidence of symptoms was absent, rounded atelectasis was detected in six patients through medical examinations. Others complained of chest pain and dyspnea. Thirteen patients displayed pleural plaques and only 2 patients revealed asbestosis. Malignant complications were discovered in 4 patients, of whom 3 showed primary lung cancer and 1 suffered acute myelocytic leukemia. In their occupational histories, 7 patients had been exposed to asbestos in the shipyards and 5 in the construction field. The mean period of the exposure was 25.1 +/- 12.7 years, and the latency period from the first asbestos exposure to the detection of atelectasis was 35.1 +/- 8.8 years. Five autopsied patients had more than 10,000 asbestos bodies in the lung, which indicated heavy exposure to asbestos. These results suggest that rounded atelectasis may appear after high-dose exposure to asbestos.

Adult↗

[Effects of rush-mat dust on the health of exposed workers].

OBJECTIVE: To evaluate the effect of exposure to rush-mat dust on the health of workers. METHODS: A cross sectional study of 661 workers (349 men, 312 women) from 35 rush-mat plants was carried out by using occupational health investigation, questionnare and physical examination. RESULTS: The geometric mean total dust concentration in the workshop was up to 20.00 mg/m3, and the geometric mean respirable dust concentration reached 8.22 mg/m3. The mean free SiO2 concentration of accumulated dust was 25.6%. The prevalence of radiographic small opacities profusion category > or = 1/0, according to the China Classification for pneumoconiosis (GB 5906-2000), and compared with the ILO 1980 system, was 2.57%. Even more, one man had category 2 pneumoconiosis with progressive massive fibrosis. However, the incidence of pneumoconiosis (1/0 at least) was correlated with work duration and dust concentration(r = 1.156, P < 0.001; r = 0.106, P = 0.006, respectively). Some positive correlations were found between the incidence of cough or expectoration and occupational exposure (r = 0.085, P = 0.028; r = 0.094, P = 0.016, respectively). CONCLUSION: To our knowledge, this is the first report of rush pneumoconiosis in China. The results have offered the possibility of a dose-response relationship between rush-mat dust and pneumoconiosis. More investigation in this area is need.

Aluminum Silicates↗

Gingival metastasis in lung cancer.

Gingival metastasis is an extremely rare manifestation of lung cancer, and exhibits rapid growth with various clinical symptoms. Physicians must appropriately manage patients with lung cancer who develop gingival metastasis. Clinical records of patients with lung cancer treated at the Department of Internal Medicine II, Okayama University Hospital, between 1976 and 1998 were retrospectively reviewed. The medical literature was searched by Medline to identify reports of gingival metastasis from lung cancer. Three of 729 (0.41%) lung cancer patients developed gingival metastasis in our hospital between 1976 and 1998, and 9 additional cases of this type of metastasis were found in the literature. All were male, and median age was 57.5 years (range, 47 to 70). There were no clear correlations between development of gingival metastasis and either histologic type or location of the primary lesion. Chemotherapy or radiotherapy was effective for treatment of gingival metastasis, and the quality of life was improved. However, survival after development of gingival metastasis was very short, with median survival of only 4 months.

Aged↗