No abstract

Objective. To investigate the association between human T lymphotropic virus type I (HTLV‐I) infection and rheumatoid arthritis (RA) in Nagasaki, an area highly endemic for HTLV‐I infection. Methods. Sera from 113 female patients with RA and 19,796 female blood donors were screened for anti–HTLV‐I antibodies with a gelatin particle agglutination kit and confirmed using an immunoblotting kits. Results. The age‐adjusted summary odds ratio of HTLV‐I infection among RA patients, as compared with blood donors, was 2.8 (95% confidence interval [95% CI] 1.8–4.6). The etiologic fraction, i.e., the proportion of RA in the study population that is attributable to HTLV‐I infection, was estimated to be 13.2% (95% CI 5.1–21.2). There was no significant difference in the clinical and laboratory findings between HTLV‐I–infected and HTLV‐I–uninfected RA patients. Conclusion. These epidemiologic findings support the idea that HTLV‐I infection is a risk factor for RA, and suggest that ∼13% of the cases of RA in females living in Nagasaki are associated with HTLV‐I infection.

A prospective follow-up study was carried out to assess the prognosis of renal tubular function after reduction of environmental cadmium exposure. Time-related changes in urinary beta 2-microglobulin and cadmium excretion were followed from 1979 to 1989 in 102 residents of a cadmium-polluted area in Nagasaki, Japan. The average dietary cadmium intake among the study population was more than 200 micrograms/d in 1969, which decreased to approximately half that amount in 1983 because cadmium-polluted paddy fields were replaced with new soil in 1981. The geometric mean urinary beta 2-microglobulin concentration for 28 subjects aged 40 y or older in 1979 increased from 1,135.8 micrograms/g creatinine in 1979 to 1,999.7 micrograms/g creatinine in 1989. A similar tendency was also observed in 16 subjects with urinary beta 2-microglobulin concentrations greater than 1,000 micrograms/g creatinine in 1979, although the statistical significance of the difference did not reach the 5% level, probably because of the small sample size. In 48 persons examined in 1982, 1986, and 1989, the geometric mean of urinary cadmium concentration decreased from 8.49 micrograms/g creatinine in 1982 to 6.03 micrograms/g creatinine in 1989. The tendency for increasing beta 2-microglobulin excretion observed in the present study could not be explained by aging alone. Thus, it was concluded that renal tubular dysfunction caused by environmental cadmium was irreversible and slowly progressive, even after reduction of exposure. Six of 8 subjects who had severe renal dysfunction and who were included in the study died before 1986 and could not be followed. The implication of loss of subjects because of death is also discussed.

Cadmium (Cd) from a zinc mine polluted Jinzu River basin, Toyama prefecture and produced a disease with severe bone pain (Itai-itai disease), from the early part of the 20th century. Cd caused renal tubular dysfunction and osteomalacia accompanied by osteoporosis. The main symptoms of the disease were bone pain, pseud fracture (Looser's zone), fracture, and renal tubular dysfunction. The pollution of paddy-field soil by Cd still remains and our epidemio1ogica1 studies of the inhabitants living in the Cd-polluted areas show the presence of renal tubular dysfunction and decrease of bone mass; characteristic of Itai-itai disease.

New insights into the immunology and genetics of malignant lymphomas have allowed the recognition of new entities and the refinement of previously recognized disease categories. The relative incidence of these subtypes of malignant lymphoma is also known to differ according to geographic location. In order to clarify the current status of malignant lymphomas in Japan and the relative incidences of their subtypes, 3194 patients were classified according to the new World Health Organization (WHO) classification. Among these were 3025 cases (94.71%) of non‐Hodgkin's lymphoma (2189 cases (68.53%) of B‐cell lymphoma, 796 cases (24.92%) of T‐cell lymphoma) and 141 cases (4.41%) of Hodgkin's lymphoma. The incidences of the major subtypes of non‐Hodgkin's lymphoma were 33.34% for diffuse large B‐cell lymphoma, 8.45% for marginal zone B‐cell lymphoma of mucosa‐associated lymphoid tissue (MALT) type, 8.05% for plasma cell myeloma, 7.45% for adult T‐cell leukemia/lymphoma (ATLL), 6.7% for follicular lymphoma, 6.67% for peripheral T‐cell lymphoma of unspecified type, 2.79% for mantle cell lymphoma, 2.6% for nasal and nasal‐type T/NK cell lymphoma, 2.35% for angioimmunoblastic T‐cell lymphoma, and 2.35% for precursor B‐cell lymphoblastic leukemia/lymphoma, in decreasing order. The other subtypes comprised less than 2%, mainly precursor T‐cell lymphoblastic lymphoma/leukemia (1.72%), anaplastic large‐cell lymphoma of T‐ and null‐cell types (1.53%), and B‐cell chronic lymphocytic leukemia/small lymphocytic lymphoma (1.31%). The incidence of ATLL was influenced by its high percentage (19.20%) in the south‐western Japanese island, Kyushu, an endemic area of human T‐cell leukemia virus type 1 (HTLV‐1), but which appeared to be lower than that in a previous study. The nodular sclerosis and mixed cellularity types of Hodgkin's disease occupied 1.78% and 1.63%, respectively. These data are distinct from those in Western countries and similar in several ways to those in the East, although the relatively high rate of ATLL was attributed to the geographical difference in the etiologic factor, HTLV‐1.

Urinary #,-microglobulin (/,-m) concentration was determined by radioimmunoassay with Phadebas /2-microtests (Pharmacia/Shionogi, Osaka), and urinary total amino nitrogen concentration by the trinitrobenzene sulphonic acid method.In August 1990, we checked vital status of the 230 participants in the health surveys. The observation period was from the date of the initial examination to the date of death or transfer or 1 August 1990. Of 230 subjects in the cohort, 88 had died and three had moved out of the study area. The total number of observation person-years was 2700-7.Results and discussion The mean age of the study population at the time of initial examination was 61-9 (standard deviation (SD) 11-8) for men and 63-5 (SD 12-7) for women.The geometric mean ofurinary #,2-M concentration at the initial examination was 418-3 (SD 4 88) pg/g creatinine for men and 642-2 (SD 6-41) pg/g creatinine for women. The geometric mean urinary total amino nitrogen concentration was 14-1 (SD 1-48) mmol/g creatinine for men and 16-7 (SD 1 51) mmol/ g creatinine for women.All subjects were dichotomised according to their urinary #,-m concentration.

A retrospective cohort study was carried out to clarify the effect of exposure to environmental cadmium (Cd) on mortality. A total of 256 residents aged 50 years or older, living in Sasu, a Cd-polluted area in Tsushima Island in Nagasaki Prefecture, Japan, were followed from July 1979 to February 1989. The expected number of deaths calculated was based on the sex-and age-specific mortality rate in Tsushima Island in 1985. In Sasu residents of both sexes with urinary R2-microglobulin (M2-m) concentration greater than 1,000 pug/g creatinine in 1979, observed deaths were greater than expected. However, the p value of the difference was less than 0.05 only in men. The relationships of age, mean blood pressure, urinary /32-m and urinary Cd concentration to mortality were examined using Cox's proportional hazards model. Urinary R2-m was independently and significantly related to mortality in men but not in women. The results suggest an association between Cd-induced renal tubular dysfunction and mortality.

A community‐based cohort study was conducted to clarify the risk of human T‐cell leukemia virus type I (HTLV‐I) infection for cause‐specific deaths. A total of 1,997 individuals (751 men and 1,246 women) aged 30 or older in A‐IsIand, Nagasaki Prefecture, Japan who had voluntarily attended annual mass health examinations, including serum HTLV‐I antibody test, were followed up for a mean period of 5.3 years. In a Cox proportional hazards analysis adjusted for age at baseline, the HTLV‐I seropositivity was found to be associated with mortality from all causes in men (hazard ratio (HR) 1.89; 95% confidence interval (CD 1.01–3.54) and women (HR 1.94; 95% CI 1.16–3.22). When the effects of 2 deaths (1 man and 1 woman) from adult T‐cell leukemia/lymphoma (ATL) were excluded, the mortality risk decreased slightly but was still significantly or marginally significantly greater than 1 in both men (HR 1.77; 95% CI 0.93–3.37) and women (HR 1.87; 95% CI 1.12–3.12). Further analysis of cause‐specific deaths revealed a significant increase in the risk for non‐neoplastic diseases but not for neoplasms excluding ATL. These findings suggest that long‐term HTLV‐I infection represents a health hazard greater than just that for the development of ATL. It was difficult, however, to draw a conclusion regarding the association between HTLV‐I infection and cancer risk, because the number of cancer deaths was small and the incidence of cancer was not investigated.