Objectives: Cytokines are critical regulatory molecules that circulate in blood at measurable levels. However, the epidemiology of serum cytokine levels in healthy populations is still limited, particularly for Japanese populations. The objective of this study was to examine the relation between serum cytokine levels and common laboratory tests in a healthy Japanese population. Methods: We studied serum levels of six cytokines (interleukin-4 (IL-4), IL-5, IL-6, IL-10, interferon-γ (IFN-γ), granulocyte-macrophage colony-stimulating factor (GM-CSF)) in a healthy Japanese population using a sensitive chemiluminescence ELISA (CL-ELISA). We examined the relations between serum cytokine levels and common laboratory tests using multiple regression analysis. We were particularly interested in potential relations between serum cytokine levels and C-reactive protein (CRP) in light of its relation to the risk of cardiovascular events. We also investigated the relation between cytokine levels, alcohol consumption and smoking. Results: After adjusting for the influence of other cytokines and laboratory tests, the serum level of IL-4 was associated with IL-5 and GM-CSF. In addition to IL-4, IL-5 was also associated with IL-10 and IFN-γ. IL-6 was associated with IL-10 and IFN-γ, and IL-10 and IFN-γ were associated with GM-CSF. CRP was significantly negatively associated with serum IL-4 level. IL-6 was weakly correlated with alcohol consumption level in this population. IL-5 among smokers tended to be lower than that among nonsmokers. Conclusions: Close relations among serum cytokine levels were observed in a healthy population. It is interesting that the level of IL-4, an anti-inflammatory cytokine, was inversely related to CRP level, suggested to be a marker of inflammation.
Serum ; Cytokines ; Interleukin-4 ; Japanese language ; Interleukin-10

To determine whether the ethlenbisdithiocarbamate fungicides, zineb, manzeb and maneb affect the N-methyl-D-aspartate (NMDA) receptor in rat brain membranes, we performed a binding assay using [3H]MK-801, a noncompetitive NMDA receptor antagonist. Displacement studies were conducted using well washed membranes to exclude the effect of endogenous acidic amino acids on the binding of [3H]MK-801. In both the presence or absence of added glutamate and glycine in the assay buffer, the dose-response curve indicated that zineb enhanced the binding in a concentration range of 100-500 μM. However, the displacement curves indicated that manzeb and maneb inhibited the binding in a concentration range of 10-500 μM. The addition of 50 μM glutamate and glycine to the assay medium increased binding by 5-20% above the control in a concentration range of 0.1-100 μM. No rats injected with zineb, manzeb, maneb (100 mg/kg, ip) showed any characteristic toxic signs or any significant weight changes within 24 hrs. Estimation of [3H]MK-801 binding to unwashed membranes from intoxicated rat brains revealed no marked change in Bmax or Kd values for 24 hrs following fungicide administration.
binding ; Upper case emm ; Fungicide, NOS ; MK-801 ; assay

Recently, patient safety has become a social concern in Japan. Even though cases of “incidents” and “accidents” by interns have been collected and analyzed in each hospital, few published reports have concerned teaching hospitals. The purpose of this study was to identify the incidence of “incidents” and “accidents” by first-year and second-year interns in Japan.
1) In August 2005, a questionnaire was mailed to 231 interns at 14 teaching hospitals. A total of 192 interns participated in this study, with a response rate of 83.1%.
2) The number of cases of “incidents” and “accidents” involving interns since the start of their training was collected.An “incident” was defined as an error that was prevented before occurrence, whereas an “accident” was defined as an unplanned, unexpected, and undesired event with adverse consequences.
3) Among first-year interns, “incidents” occurred at a rate of 0.79 per resident-month (95% confidence interval [CI]: 0.30-1.28), while “accidents” were observed at a rate of 0.13 per resident-month (95% CI: 0.06-0.20).
4) Among second-year interns, “incidents” occurred at a rate of 0.24 per resident-month (95% CI: 0.14-1.34), and “accidents” were observed at a rate of 0.06 per resident-month (95% CI: 0.01-0.11).
5) There was no significant difference in the number of cases of “incidents” and “accidents” in regards to sex, age, or the number of beds of teaching hospitals.

OBJECTIVETributyltin (TBT) compounds have been widely used as antifouling agents for shipbottom paint. The immune system is a target of TBT intoxication. We evaluated the effects of TBT chloride in macrophages, which have critical roles in the immune system, using a murine macrophage lineage cell line, J774.1,in vitro.

METHODSWe examined tumor necrosis factor α (TNFα), interleukin-1β (IL-1β) andc-jun mRNA expression in J774.1 cells. The effects of TBT on the apoptosis of J774.1 cells were examined by determining the percentage of TUNEL-positive cells and caspase-3 activity.

RESULTSThe mean values of the viabilities of J774.1 cells exposed to TBT decreased dose-dependently. The relative mRNA expression of TNFα increased dose-dependently, however, that of IL-1β was not significantly different among the groups. The mean percentage of TUNEL-positive cells increased dose-dependently. Increases in the caspase-3 activities of J774.1 cells were observed in the groups exposed to higher concentrations of TBT. The mean value of relative mRNA expression of c-Jun transcription factor increased dose-dependently.

CONCLUSIONSThe increases in the percentage of TUNEL-positive cells and in caspase-3 activity suggested that exposure to TBT induces apoptosis of J774.1 cells. The increases in the mRNA expression of TNFα andc-jun by TBT may be related to apoptosis in macrophages.

OBJECTIVESCytokines are critical regulatory molecules that circulate in blood at measurable levels. However, the epidemiology of serum cytokine levels in healthy populations is still limited, particularly for Japanese populations. The objective of this study was to examine the relation between serum cytokine levels and common laboratory tests in a healthy Japanese population.

METHODSWe studied serum levels of six cytokines (interleukin-4 (IL-4), IL-5, IL-6, IL-10, interferon-γ (IFN-γ), granulocyte-macrophage colony-stimulating factor (GM-CSF)) in a healthy Japanese population using a sensitive chemiluminescence ELISA (CL-ELISA). We examined the relations between serum cytokine levels and common laboratory tests using multiple regression analysis. We were particularly interested in potential relations between serum cytokine levels and C-reactive protein (CRP) in light of its relation to the risk of cardiovascular events. We also investigated the relation between cytokine levels, alcohol consumption and smoking.

RESULTSAfter adjusting for the influence of other cytokines and laboratory tests, the serum level of IL-4 was associated with IL-5 and GM-CSF. In addition to IL-4, IL-5 was also associated with IL-10 and IFN-γ. IL-6 was associated with IL-10 and IFN-γ, and IL-10 and IFN-γ were associated with GM-CSF. CRP was significantly negatively associated with serum IL-4 level. IL-6 was weakly correlated with alcohol consumption level in this population. IL-5 among smokers tended to be lower than that among nonsmokers.

CONCLUSIONSClose relations among serum cytokine levels were observed in a healthy population. It is interesting that the level of IL-4, an anti-inflammatory cytokine, was inversely related to CRP level, suggested to be a marker of inflammation.

OBJECTIVEThe aim of this study was to investigate the effect of tributyltin (TBT) compound onN-methyl-D: -aspartate (NMDA) receptors in the brains of preweanling mice.

METHODSPregnant ICR mice were exposed to TBT chloride at concentrations of 0, 15, and 50 ppm in water. Male offspring were sacrificed at 1, 2 and 3 weeks after birth. Mouse brain membranes were prepared from cerebral cortices, and the specific binding of [(3)H]MK-801 to an NMDA receptor was determined by radioligand binding assay.

RESULTSThe mean body weight of preweanling mice of the 50 ppm dose group decreased by 17-25% (p<0.01) at 1, 2 and 3 weeks of age, compared with that of preweanling mice of the corresponding control group. The [(3)H]MK-801 binding level significantly decreased (p<0.05) in the 15 ppm F1 group at 1 week and in the 15 ppm and 50 ppm F1 groups at 3 weeks of age, compared with that in the corresponding control F1 group.

CONCLUSIONSThe exposure to TBT via placenta and dam's milk seriously affected not only the growth of preweanling mice, but also the F1 cerebral NMDA receptors involved in memory and learning.

OBJECTIVESThe toxicity of microglass fibers (MG), one of the man-made mineral fibers, has not been sufficiently evaluated. The aim of the current study was to evaluate the cytotoxicity of MGin vitro.

METHODSAlveolar macrophages were obtained from the bronchoalveolar lavage of male F344/N rats. The macrophages were exposed to MG at concentrations of 0, 40, 80, 160 and 320 μg/ml. The effects of MG on the macrophages were examined by cell magnetometry, LDH assay and morphological observation.

RESULTSIn the cell magnetometry experiment, a significant delay of relaxation (the reduction of remanent magnetic field strength) was observed in the cells treated with 160 and 320 μg/ml of MG in a dose-dependent manner. A significant increase in LDH release was also observed in the cells with 160 and 320 μg/ml in a dose-dependent manner. Changes in the cytoskeleton were observed after exposure to MG by immunofluorescent microscopy using an α-tubulin antibody.

CONCLUSIONSThe cytotoxicity of MG on alveolar macrophages was demonstrated with cell magnetometry. The mechanism of the toxic effects of MG was related to cytoskeleton damage.