Yukinori Kusaka

Comparative toxicity of standard nickel and ultrafine nickel in lung after intratracheal instillation.

Comparative Toxicity of Standard Nickel and Ultrafine Nickel in Lung after Intratracheal Instillation: Qunwei Zhang, et al.; Department of Environmental Health, School of Medicine, Fukui Medical University—A comparison was made of the bronchoalveolar lavage fluid (BALF) response to ultrafine nickel (Uf‐Ni) and standard‐sized nickel (Std‐Ni). Rats were intratracheally instilled with 0, 0.1, 0.5, 1 and 5 mg Uf‐Ni and Std‐Ni, respectively. At 3 d after instillation, the body weight and wet lung weight were determined. At the same time, BALF was analyzed for lactate dehydrogenase (LDH), total protein (TP), tumor necrosis factor‐alpha (TNF‐alpha), and total cell and differential cell counts. The results showed that indicators of lung injury and inflammation in BALF were markedly raised with increased Uf‐Ni and Std‐Ni for each from 0 to 1 mg, and there were no differences in the indices between instillation of Uf‐Ni at 1 mg and 5 mg. The results also showed that the effects of Uf‐Ni on the indices were significantly higher than those of Std‐Ni. Additional groups of rats were intratracheally instilled with 1 mg of Uf‐Ni or Std‐Ni, and wet lung weight and BALF profiles were analyzed at 1, 3, 7, 15 and 30 d later. The effect of Uf‐Ni and Std‐Ni on indices that can be presumed to reflect epithelial injury and permeability (LDH or TP), and release of proinflammatory cytokine (TNF‐alpha) were increased throughout the 30 d post‐exposure and the effects of Uf‐Ni on these indices were significantly higher than those of Std‐Ni from 1 to 30 d after instillation. Moreover, the number of neutrophils and LDH activity in BALF of rats after exposure to Uf‐Ni were significantly greater than those of Std‐Ni‐exposed rats up to 30 d after instillation. Our findings suggest that Uf‐Ni has a much more toxic effect on the lung than St‐Ni, but the mechanism remains to be elucidated.

Healthy lifestyles are associated with higher natural killer cell activity

BACKGROUND To investigate the association of individual lifestyle with immune response against tumors, we assayed peripheral blood lymphocytes of 62 healthy males ranging in age from 30 to 60 years for natural killer (NK) cell activity, which is the first line of defense against tumors, and for frequencies of NK cell subsets. METHODS The NK cell activity was determined by 51Cr release assay, and NK cell subsets were counted using surface antigens (CD16, CD57) which recognize NK cell subgroups with different cytolytic potentials. Subjects were classified into groups reporting good, moderate, and poor lifestyles according to their responses on a questionnaire regarding eight health practices (tobacco smoking, alcohol consumption, hours of sleep, physical exercise, eating breakfast, balanced nutrition, hours of work habits, and mental stress). RESULTS Individuals reporting good lifestyle habits were found to have the highest NK cell activity and it was significantly higher than the NK cell activity in those reporting poor lifestyle habits. Those reporting good health practices regarding smoking and physical exercise showed significantly higher NK cell activity at an effector-to-target-cell ratio of 40:1. CONCLUSIONS The higher NK cell activity among individuals reporting good lifestyle practices may reflect an increase in the cytolytic potential of NK cell activity within the CD16+, CD57- subset.

Biological monitoring of cobalt exposure, based on cobalt concentrations in blood and urine

SummaryCobalt exposure level and its concentrations in blood and urine were determined for 175 hard metal workers. For control data, the cobalt concentrations in blood and urine were measured for 20 office workers. The exposed workers had significantly higher cobalt concentrations in both blood and urine. The relationships between exposure level and cobalt concentrations in blood and urine were linear and positive. The results clearly showed that the cobalt concentration in the blood or urine can be used as an exposure indicator. With cobalt exposure of 100 μg/m3, the cobalt concentration was 0.57 to 0.79 μg/dl in blood and 59 to 78 μg/l in urine with 95% confidence limits. In workers using respirators, the cobalt concentrations in the blood and urine decreased to 2/5 and 1/8, respectively, of those not using respirators.

Hard metal asthma: cross immunological and respiratory reactivity between cobalt and nickel?

Eight asthmatic patients with hard metal asthma due to cobalt underwent bronchial provocation challenge with nickel sulphate. Seven patients developed a fall in FEV1 of 20% or more after inhaling nickel sulphate, four showing an immediate response and three a late response. Eight control subjects, including six asthmatic patients, with no history of hard metal exposure, showed no bronchoconstriction in response to a provocation challenge with nickel sulphate. Specific antibodies to nickel conjugated human serum albumin were present in four of the eight patients with sensitivity to cobalt conjugated human serum albumin but were absent from the serum of 60 unexposed asthmatic patients and 25 exposed symptom free workers. These results suggest that nickel as well as cobalt sensitivity plays a part in hard metal asthma.

Age, menopause, bone turnover markers and lumbar bone loss in healthy Japanese women

The change in lumbar vertebral bone mineral density (BMD) during a 2-year study period was examined in 167 healthy middle-aged and elderly Japanese women with reference to age, menopausal status and bone turnover markers at baseline. The perimenopausal and postmenopausal groups of the subjects showed a significant loss of BMD during the study period but the premenopausal women did not. The annual percent decrease of BMD (delta BMD) in the perimenopausal women (-2.40% in average) was significantly greater than that in either of the premenopausal (-0.01%) or over-all postmenopausal women (-0.85%). The subjects who had been postmenopausal for less than 10 years showed a significant bone loss. delta BMD in the postmenopausal women became less marked as the postmenopausal duration increased. The bone loss was accelerated for about 10 years after menopause. The pattern and magnitude of bone loss of Japanese women seemed to be similar to those of Caucasian women. The regression equation for delta BMD based on the bone turnover markers at baseline was shown to be significant in the postmenopausal women and the serum level of bone-specific alkaline phosphatase isoenzyme had a significant relation to delta BMD. However, this equation accounted for only 17.3% of the total variance of delta BMD and, hence, its validity was not sufficiently high for the prediction of bone loss in clinical settings.

The existence of specific antibodies to cobalt in hard metal asthma

Twelve workers with hard metal asthma diagnosed on the basis of peak flow diaries and positive bronchial reactions to cobalt chloride (CoCl2) were studied for sensitization by detection of specific antibodies to radioactive cobalt (57Co), cobalt‐conjugated human serum albumin (Co‐HSA) and cobalt‐conjugated exchange resin (Co‐resin). Their IgE titres ranged from 73 to 1500 IU/ml and eight were atopic individuals. Sixty serum samples from asthmatic patients with IgE titres of 14–4300 IU/ml were studied as controls in all tests. Eleven of twelve subject sera that selectively bound to 57Co after incubation with saturated ammonium sulphate (>232 c.p.m., P<0.01) were divided into three groups: (1) six sera showing evidence of specific IgE antibodies to Co‐HSA (>673 c.p.m., P<0.01) without those to Co‐resin; (2) one serum giving a positive radio‐allergosorbent test (RAST) only to Co‐resin (>417 c.p.m., P<0.01), and (3) four sera that were negative for two antigenic agents (Co‐HSA, Co‐resin). These results suggest that the subjects had occupational asthma due to hard metal exposure from cobalt sensitivity. An immuno‐allergic mechanism mediated by specific IgE antibodies to cobalt was confirmed to be responsible for the development of hard metal asthma, with the possibility of some role of the reaction without reagins.

Specific IgE antibodies to nickel in workers with known reactivity to cobalt.

Twenty‐one workers with hard metal asthma, including eight atopics, diagnosed on the basis of peak flow diaries and positive reaction to cobalt chloride (CoCl2) and/or nickel sulphate (NiSO4) in skin and provocation tests were studied for sensitization by detection of specific antibodies to nickel‐conjugated human serum albumin (Ni‐HSA), and nickel‐conjugated exchange resin (Ni‐resin). Their results were compared with those of sera obtained from control sera from 60 asthmatic patients and pair‐matched asymptomatic control workers in the hard metal plant. In the RASTs (radioallergosorbent tests), sera from the same six subjects developed positive reactions both to Ni‐HSA (RAST index > 2.0, P < 0.01) and Ni‐resin (RAST index > 2.0, P < 0.01), while the counts measured for the others of the 15 subjects (RAST index < 1.52) were about the same as those for control groups (RAST index < 1.58). Subject HSA RAST and resin RAST results (378.52 c.p.m. in HSA RAST and 324.56 in the resin RAST) were about the same as those of the control sera (388.65 c.p.m. and 398.59 c.p.m., respectively). There was no difference in the prevalence of smoking habit and high IgE between Ni‐RAST positive and negative subjects. However, subjects with simultaneous sensitivity to nickel and/or cobalt still developed asthmatic attacks following medications, while those without sensitivity to these metals were almost symptom free. The positive sera had simultaneous sensitivity to both cobalt and nickel, suggesting the presence in them of specific IgE antibodies to nickel playing some role in the aetiology of hard metal asthma.

Estimation of trunk muscle parameters for a biomechanical model by age, height and weight.

Estimation of Trunk Muscle Parameters for a Biomechanical Model by Age, Height and Weight: Akihiko Seo, et al. Department of Intelligent Systems, Graduate School of Engineering, Tokyo Metropolitan Institute of Technology—To establish more accurate equations for estimating the moment arm length and cross‐sectional area of the erector spinae and rectus abdominis muscles, the effects of height, weight and age on those muscles were analyzed by using a high‐order polynomial equation. Data on the moment arm length and cross‐sectional area at L3/ 4 were obtained from MRI images of 152 males and 98 females. The statistical model used in this study has any combination of up to third‐order independent variables for age, height and weight. The effective independent variables were selected by the forward step method of multiple regression analyses. The results of multiple regression analyses showed that the polynomial equations for the moment arm length of erector spinae in both genders, and that for the rectus abdominis in males, contained all three variables of age, height and weight. That for the moment arm length of female rectus abdominis contained the variables of weight and age. The multiple correlation coefficients of the erector spinae and rectus abdominis were 0.355 and 0.650 for males, 0.364 and 0.411 for females, respectively. The equations for the cross‐sectional area of the erector spinae in both genders, as well as that for male rectus abdominis contained only one variable (weight). The multiple correlation coefficients of the cross‐sectional area of the erector spinae were 0.576 for males and 0.469 for females. The cross‐sectional area of the female rectus abdominis had no effective variables.

Occupational Allergy in Medical Doctors

Occupational Allergy in Medical Doctors: Kazuhiro Sato, et al. Department of Environmental Health, School of Medicine, University of Fukui— Allergic diseases have increased in many developed countries including Japan. Doctors are also at risk for allergic diseases from exposure to allergens in working conditions and hospital environments. We investigated the factors relating to occupational allergy in doctors. Self‐administered questionnaires were mailed to all doctors (n=895) who had previously graduated from School of Medicine, Fukui Medical University. Data from 307 responders (response rate: 34.3%, male 241, female 66, mean age ± S.D., 30.8 ± 4.2) were analyzed. Eighty‐nine doctors stated that they had occupational allergy including contact dermatitis, allergic rhinitis and/ or asthma. Fifty‐four had contact dermatitis caused by surgical gloves; 77 had contact dermatitis from disinfectants, e.g. 23 from chlorhexidine gluconate; 21 from povidone iodine; and 15 from ethanol. Fifteen doctors experienced allergic rhinitis and/or asthma caused by handling laboratory animals. Univariate analysis showed that profession (surgical doctors) and past histories of allergic diseases (rhinitis, sinusitis, or atopic dermatitis) were significantly related to occupational allergy in doctors, but that gender, smoking or physical exercise were not significantly related to it. A logistic regression analysis showed that past histories of allergic diseases and the profession of surgical doctors were significantly related to occupational allergy, but that gender, age or smoking were not significantly related to it. The results of the present study suggest that past history of allergic diseases is a factor predisposing to occupational allergy in doctors. It is necessary and possible to extend more prophylactic measures for doctors, especially for surgeons, because exposure to responsible agents and materials for them can be more frequent.

Metal-Induced Lung Disease: Lessons from Japan's Experience

Metal‐Induced Lung Disease: Lessons from Japans Experience: Yukinori Kusaka, et al. Department of Environmental Health, School of Medicine, Fukui Medical University—Metals inducing occupational respiratory diseases, e.g. metal fever, acute and chronic pneumonia, asthma, bronchitis, chronic obstructive lung disease, pulmonary fibrosis and lung cancer are described. The metals mentioned are the following: aluminum, antimony, arsenic, barium, beryllium, cadmium, chromium, cobalt, copper, iron, lithium, manganese, mercury, nickel, platinum, rhodium, rare earth metals, titanium, uranium, vanadium, welding, zinc, zirconium. With respect to these metals, mechanism of the disease, disease statistics, case reports, diagnostic methods, patho‐physiology of the disease, and preventive measures including occupational exposure limits are also described. Experience in Japan on these issues is given in detail.