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Effects of periodic administration of Nocardia rubra cell-wall skeleton on immunoglobulin production and B-cell-stimulatory factor activity in vitro in workers at a poison gas factory.

The former workers at the Okunojima poison gas factory (poison gas workers) are a high-risk group for malignant neoplasms and show abnormalities in cellular immunity. At the same time, poison gas workers often have chronic respiratory diseases, such as chronic bronchitis, and are highly susceptible to respiratory infections. To explore the possibility of immunological cancer prevention, we have periodically administered 200 micrograms Nocardia rubra cell-wall skeleton (N-CWS) to poison gas workers once every 3 months since December 1978. During this period, we noted a significantly lower incidence of influenza among poison gas workers receiving N-CWS than in those not receiving the drug during the influenza epidemic. This finding suggested that the administration of N-CWS enhanced the resistance of these workers to infections. Therefore, periodical administration of N-CWS to poison gas workers was considered to enhance the reduced T-cell function of normalizing antibody production by stimulating the production of B-cell-stimulatory factor (BSF). In the present study, to clarify the mechanism of immunosuppression in the poison gas workers and to examine the effects of continual administration of N-CWS on this condition, we compared the immunoglobulin production and the proliferative and differentiative activities of B-cell-stimulatory factor (BSF) of peripheral blood mononuclear cells (PBMC), in poison gas workers treated or not treated with N-CWS. Comparisons were also made with age-matched healthy controls. In the untreated poison gas workers, immunoglobulin and BSF production of PBMC were reduced as compared with the control group. On the other hand, in the poison gas workers receiving N-CWS, immunoglobulin and BSF production of PBMC were restored nearly to the control level. These results show that in vitro antibody production in the poison gas workers was reduced and that a reduction in BSF production of T cells was one of its causes.

Adjuvants, Immunologic↗

Effects of Nocardia rubra cell wall skeleton on lymphocyte subsets in former poison gas factory workers.

Peripheral blood lymphocyte subsets were determined in former workers of the Okunojima Poison Gas Factory (poison gas workers) having a high incidence of lung cancer, and the effect of administration of Nocardia rubra cell wall skeleton (N-CWS) was studied. In poison gas workers not receiving N-CWS, both the percentage and absolute number of Leu-2a+ cells were significantly increased as compared with normal controls, while both the percentage and absolute number of Leu-7+ cells as well as the Leu-3a/Leu-2a ratio were significantly decreased. In poison gas workers receiving N-CWS, the percentage of Leu-2a+ cells was significantly decreased when compared with poison gas workers not receiving N-CWS, while the percentage of Leu-1+ cells and both the percentage and absolute number of Leu-7+ cells as well as the Leu-3a/Leu-2a ratio were significantly increased. When N-CWS was administered to poison gas workers, the percentage of Leu-2a+ cells significantly decreased, with a minimum two weeks after administration, while the percentage of Leu-3a+ and the Leu-3a/Leu-2a ratio significantly increased and the percentages of Leu-1+ and Leu-7+ cells also increased. Furthermore, the absolute number of Leu-3a+ cells increased markedly with a peak two weeks after administration. The absolute numbers of both Leu-1+ cells and Leu-7+ cells as well as total lymphocytes also significantly increased, but that of Leu-2a+ cells showed hardly any change. It is considered that a single administration of N-CWS transiently corrects the abnormality of lymphocyte subsets, and that repeated administration of N-CWS once every three months may maintain the lymphocyte subsets of poison gas workers at normal levels.

Aged↗

Effects of Nocardia rubra cell wall skeleton on interleukin 2 production and lymphocyte proliferation in former poison gas factory workers.

Phytohemagglutinin (PHA)-induced interleukin 2 (IL-2) production and lymphocyte proliferation were measured in former workers of the Okunojima Poison Gas Factory (poison gas workers), who have a high incidence of lung cancer, and the efficacy of administration of Nocardia rubra cell wall skeleton (N-CWS) was studied. In comparison with normal controls and poison gas workers receiving N-CWS, lymphocyte proliferation in poison gas workers not receiving N-CWS showed a significant decrease, while IL-2 production showed a slight though not statistically significant decrease. When N-CWS was administered to poison gas workers, IL-2 production and lymphocyte proliferation were significantly elevated, with a peak two weeks after administration. N-CWS, by elevating IL-2 production of lymphocytes, is considered to have improved the depression of lymphocyte proliferation.

Adjuvants, Immunologic↗

[Late lesions due to poison gas in survivors of the Iraqi poison warfare against the Kurdish people].

The purpose of this contribution was to demonstrate the extent of destruction of the human being by toxic war gases especially mustard gas. In spite of being several kilometers away from the scene of explosion, the surviving patients showed different residual symptoms of poison gas effects especially within the range of the skin, the eyes and the respiratory tract. There has been no effective treatment of these lesions found till nowaday and there would be perhaps none in a near future. No pathogenic organism already known could ever give rise to such destruction of the organism within a very short time. To make a comparison, the epidemic plague of 1349 (also called the huge plague year) should be mentioned here. It claimed 800 victims daily in Paris, whereas the disastrous event in the city of Halabja caused the death of 5000 people within less than 10 minutes. That is to say 8 times more than the daily victims of one of the last big epidemics of the middle ages. It is hopeless to assume that the production of these and similar destructive agents in the long run will be terminated. It is to be hoped however, that this horrible weapon never be delivered to persons who make use of it unscrupulously, as is already happened with the Kurdish people in Iraq.

Chemical Warfare↗

[Follow-up studies on chronic obstructive pulmonary disease among Ookunojima poison gas workers].

A high prevalence of chronic bronchitis has been reported among former employees of a poison gas factory in Ookunojima. The author has studied changes in clinical features by analyzing chest X-ray, sputa and respiratory function in 72 cases whose clinical courses could be observed for the 10 year period from 1981 to 1991. FEV1.0 in the patients with emphysematous change on chest X-ray was significantly decreased as compared to that of patients with inflammatory change and those with normal findings. FEV1.0 in the obstructive and infectious-obstructive type groups, in terms of clinical classification of chronic bronchitis, was significantly decreased as compared to that of simple and inflammatory types. These results show that the obstructive ventilation disorder in these two groups is progressive. Next, the author analyzed CT findings of the whole lung in 93 cases, including the former 72 cases. %(I-E) represents the alteration ratio of whole lung field CT numbers during full inspiration and full expiration. %(I-E) in the emphysematous group was significantly decreased as compared to the other two groups. %(I-E) showed a good correlation with FEV1.0 (r = 0.645), FEV1.0% (r = 0.500) and V50/V25(r = 0.523). This parameter was considered to be useful for evaluation of the obstructive ventilation disorder in these cases. The chronic bronchitis in these poison gas workers has been reported to be predominantly inflammatory and to have a variable clinical course. However, our results show that progression of the obstructive ventilation disorder caused by emphysematous change produces long term deterioration of pulmonary function in poison gas workers.

Aged↗

Somatic mutation in peripheral lymphocytes of former workers at the Okunojima poison gas factory.

The former workers at the Okunojima poison gas factory comprise a high risk group for malignant tumors such as respiratory tract cancer. Demonstration of injury to somatic cell genes in this group may provide important data for evaluating the association between mustard gas and malignant tumors. So we measured the frequency of T lymphocytes lacking the hypoxanthine guanine phosphoribosyl transferase (HGPRT) activity, by cloning with interleukin 2 (IL2). In this study, we performed cloning of T lymphocytes lacking the HGPRT activity using recombinant IL2 (rIL2) and observed an increased frequency of somatic mutation in poison gas workers who had had more chances to be exposed to mustard gas and those who had worked for a longer period. This result suggested that inhalation of small amounts of mustard gas damaged somatic cell genes, resulting in carcinogenesis.

Aged↗

[Pulmonary fibrosis following nitrous gas poisoning].

Authors in the autopsy material of the Department of Forensic Medicine of Semmelweis Medical University analysed nitrous-gas-poisoning cases. In the period of 1971--1975 out of 22 223 autopsy cases one case of nitrous gas-poisoning occurred. Data of the literature are summarized. Possible pathomechanism of the nitrous gas poisoning is also discussed.

Adult↗

Former poison gas workers and cancer: incidence and inhibition of tumor formation by treatment with biological response modifier N-CWS.

Mustard gas is known to have mutagenic and carcinogenic effects on animal and human cells. In this report, 1,632 male Japanese who worked in poison gas factories at some time between the years 1927 and 1945 were studied to determine comparative risk for development of cancer, the reference population being data on Japanese males overall. The standardized mortality ratio (SMR) for lung cancer in workers directly and indirectly involved in the production of mustard gas was significantly elevated. In addition, SMR for lung cancer in worker who had worked for more than 5 years was also significantly elevated. Thus, poison gas workers who had engaged in the production of mustard gas or related work for more than 5 years are a high-risk group for lung cancer. Under the cancer preventive program, Nocardia rubra cell-wall skeleton (N-CWS) was administered to 146 former poison gas workers. During a 4.5 year observation period, development of cancers was found in 7 treated workers and 17 untreated controls. After elimination of the influence of smoking level, a significant suppression of development of cancers was noted in the N-CWS-treated workers as compared to the untreated controls. Although the molecular mechanisms of carcinogenesis in former poison gas workers remains unclear, our study proposes the possible effect of biological response modifiers in the prevention of cancer development in high-risk human subjects.

Arsenicals↗