Masatoshi Takaishi

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.

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

SummaryThe 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 µgNocardia 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.

Clinical usefulness of continuous administration ofNocardia rubra cell wall skeleton (N-CWS) in diffuse panbronchiolitis (DPB)

Eight patients with diffuse panbronchiolitis (DPB) who had repeated intractable airway infections were continuously treated withNocardia rubra cell wall skeleton (N-CWS), a biological response modifier. As a result, subjective symptoms were reduced in 6 patients. Antibiotics therapy could be discontinued completely in two patients and the dose of antibiotics could be reduced considerably in two other patients. No adverse reactions in relation to N-CWS were observed. These results suggest that N-CWS is effective in treating erythromycin-resistant DPB.

ANALYSES OF BRONCHOALVEOLAR LAVAGE FLUID (BALF) IN MRL-LPR/LPR MICE

We performed bronchoalveolar lavage (BAL) in MRL-lpr/lpr (MRL/l) and MRL- +/+ (MRL/n) mice and evaluated various cellular and humoral components of the bronchoalveolar lavage fluid (BALF) to clarify the pathogenic mechanism of pulmonary fibrosis in MRL/l mouse. The numbers of macrophages, neutrophils and lymphocytes, N-Acetyl-beta-glucosaminidase (beta-NAG), and fibronectin increased in the BALF from MRL/l mice than that from MRL/n mice, but no significant differences were observed in total protein, beta-glucuronidase, acid phosphatase, or phospholipid level. Increased fibronectin level in the BALF from MRL/l mice may be related with pathogenesis of pulmonary fibrosis.