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Biomedical subjects

F Kayama

Publications and source records attributed to F Kayama.

At least 19 recordsLinked to original sources
PubMed2000

A nuclear matrix-associated factor, SAF-B, interacts with specific isoforms of AUF1/hnRNP D.

One class of heterogeneous nuclear ribonucleoproteins (hnRNPs), AUF1/hnRNP D, consists of four isoform proteins (p45, p42, p40, and p37) which are generated by alternative splicing. The present study was therefore undertaken to clarify any isoform-specific differences in terms of their functions and nucleocytoplasmic localization. All isoforms primarily localized in the nucleus. However, heterokaryon analysis and a study using RNA polymerase II inhibitor revealed that p40/p37 exhibited a continuous shuttling between the nucleus and cytoplasm. Constant nuclear retention activity was mapped to the p45/p42-specific sequence at the C-terminal region, which is retained by alternative splicing. Using this domain as a probe, we performed a yeast two-hybrid screening and we found that scaffold attachment factor B (SAF-B), a nuclear matrix-associated protein, exhibits protein-protein interaction to this region. Colocalization of p45/p42 and SAF-B was observed as a speckle in the nucleus. Interestingly, p45/p42 isoforms appeared to act as a negative regulator in gene expression by forming a complex with SAF-B. Thus, the present study revealed that the isoform-specific functions of AUF1/hnRNP D are defined by intracellular shuttling capacity.

3T3 Cells↗
PubMed2000

Arsenic mediates cell proliferation and gene expression in the bladder epithelium: association with activating protein-1 transactivation.

Although the mechanism of action has not yet been defined, epidemiological studies have demonstrated an association between elevated arsenic levels in drinking water and the incidence of urinary bladder transitional cell carcinomas. In the current studies, we demonstrate that mice exposed to 0.01% sodium arsenite in drinking water develop hyperplasia of the bladder urothelium within 4 weeks of exposure. This was accompanied by the accumulation of inorganic trivalent arsenic, and to a lesser extent dimethylarsinic acid, in bladder tissue, as well as a persistent increase in DNA binding of the activating protein (AP)-1 transcription factor. AP-1 transactivation by arsenic also occurred in bladders of transgenic mice containing an AP-1 luciferase reporter. Consistent with these in vivo observations, arsenite increased cell proliferation and AP-1 DNA binding in a human bladder epithelial cell line. Gene expression studies using RNase protection assays, reverse transcription-PCR, and cDNA microarrays indicated that arsenite alters the expression of a number of genes associated with cell growth, such as c-fos, c-jun, and EGR-1, as well as cell arrest, such as GADD153 and GADD45. The proliferation-enhancing effect of arsenic on uroepithelial cells likely contributes to its ability to cause cancer.

Animals↗
PubMed2000

Cadmium-induced acute hepatic injury is exacerbated in human interleukin-8 transgenic mice.

It is reported repeatedly that severe hepatocellular necrosis along with infiltration of neutrophils occurs after acute cadmium exposure. Neutrophils, which migrate by the gradient of chemoattractants such as interleukin-8, are believed to play an important role in inflammation at the damaged sites. To investigate whether neutrophils aggravate or repair the liver injury induced by cadmium, we checked the hepatotoxic effects of cadmium on human interleukin-8 transgenic mice (hIL-8Tg), which overexpressed IL-8 and displayed an inability of neutrophil migration resulting from both the lack of chemotactic gradient and the downregulation of l-selectin on the surface of neutrophils. A significantly lower survival rate was observed in hIL-8Tg compared with wild-type mice after subcutaneous administration of cadmium. Evident liver injury characterized by abrupt increases in plasma GOT and GPT levels was found in hIL-8Tg at 18 h after cadmium administration. Histological examinations, including H & E staining and esterase staining, revealed the infiltration of numerous neutrophils into the damaged liver tissues in wild-type mice, and the inhibition of the neutrophil migration into the liver as well as enhanced hepatocellular necrosis in hIL-8Tg. Peripheral white blood cell and polymorphonuclear cell counts increased and reached their peaks at 12 h after cadmium administration in wild-type mice, whereas the increase in blood leukocyte counts was delayed in hIL-8Tg. There was no significant difference in the amounts of cadmium accumulated in liver and kidneys between wild-type mice and hIL-8Tg. In conclusion, an acute cadmium hepatotoxic effect was exacerbated in hIL-8Tg resulting from inhibited neutrophil migration, suggesting that migrated neutrophils can prevent aggravation of liver injury by acute cadmium administration.

Alanine Transaminase↗
PubMed1999

Inhibitory effect of natural and environmental estrogens on thymic hormone production in thymus epithelial cell culture.

The present study was carried out to assess the direct effect of natural estrogen and environmental estrogens on thymus epithelial cell (TEC) production/secretion of the thymic hormone thymosin-alpha 1 by using the technique of quantitative high-performance liquid chromatography. The presence of estrogen receptors in the TECs was also investigated. Murine TECs were cultured in the experimental DMEM medium containing various concentrations of natural or environmental estrogens, which was followed by determining the production of thymosin-alpha 1. The production of thymosin-alpha 1 by TECs was significantly inhibited by increasing concentrations of 17beta-estradiol (natural estrogen) over 3 x 10(-11) M, genistein (phytoestrogen) over 3 x 10(-9) M, coumestrol (phytoestrogen) over 3 x 10(-9) M, alpha-zearalanol (livestock anabolic) over 3 x 10(-7) and bisphenol-A (plastic) over 3 x 10(-6) M. Small amounts of estrogen receptor were present in the TECs. The above results clearly indicate that natural and environmental estrogens directly modulate TECs to produce thymic hormone probably through an estrogen receptor mechanism. Furthermore, our finding may be useful for evaluating biological effects of chemicals with estrogenic activity.

Animals↗
PubMed1998

Estrogenic xenobiotics increase expression of SS-A/Ro autoantigens in cultured human epidermal cells.

SS-A/Ro autoantibodies are detected at high levels in patients with autoimmune diseases such as systemic lupus erythematosus. It has been reported that natural estrogen is capable of inducing cell surface expression of SS-A/Ro autoantigens in human epidermal keratinocytes. In this study, we analysed, by reverse transcriptase polymerase chain reaction and immunohistochemistry, the effects of estrogenic xenobiotics (i.e. environmental estrogens) on the expression of 52-kDa SS-A/Ro autoantigen in cultured keratinocytes. At a concentration of 10 microM, various estrogenic xenobiotics derived from plants, insecticides, or detergents induced up to a 3-fold increase in 52-kDa SS-A/Ro mRNA levels in human keratinocytes compared with untreated cells. The immunohistochemistry results paralleled the reverse transcriptase polymerase chain reaction results. These findings suggest that environmental stimulation can induce the expression of autoantigens such as SS-A/Ro.

Adult↗
PubMed1998

Protective effects of a human 18-kilodalton cationic antimicrobial protein (CAP18)-derived peptide against murine endotoxemia.

CAP18 (an 18-kDa cationic antimicrobial protein) is a granulocyte-derived protein that can bind lipopolysaccharide (LPS) and inhibit various activities of LPS in vitro. The present study examined the protective effect of a synthetic 27-amino-acid peptide (CAP18(109-135)) from the LPS-binding domain of CAP18 against antibiotic-induced endotoxin shock, using highly LPS-sensitive D-(+)-galactosamine (D-GalN)-sensitized C3H/HeN mice. The antibiotic-induced endotoxin (CAZ-endotoxin) was prepared from the culture filtrate of Pseudomonas aeruginosa PAO1 exposed to ceftazidime (CAZ). Injection of CAP18(109-135) protected the mice injected with LPS or CAZ-endotoxin from death and lowered their tumor necrosis factor (TNF) levels in serum in a dose-dependent manner. Treatment with CAZ caused death of the D-GalN-sensitized P. aeruginosa PAO-infected mice within 48 h, while injection with CAP18(109-135) rescued the mice from death. In the mice rescued from death by injection with CAP18(109-135), endotoxin levels in plasma and TNF production by liver tissues were decreased but the numbers of viable infecting bacteria in their blood were not decreased significantly and remained at the levels in CAZ-treated mice. These results indicate that CAP18(109-135) is capable of preventing antibiotic-induced endotoxic shock in mice with septicemia and that the effect is due to its LPS-neutralizing activity rather than to its antibacterial activity.

Animals↗
PubMed1997

Pro-inflammatory cytokines and interleukin 6 in the renal response to bacterial endotoxin.

Pro-inflammatory cytokines, including tumour necrosis factor alpha (TNF-alpha), interleukin (IL)-1 and IL-6 are thought to play important roles in the pathophysiology of chronic kidney disorders, including glomerulonephritis. In particular, IL-6 has received considerable attention as it appears at high concentrations to promote the progression of renal disease while at lower levels may be involved in regulating repair mechanisms. As such, cytokine profiles have been examined in the kidney by either examining secretion from isolated kidney cells or quantitating plasma and urinary levels in experimental models of glomerulonephritis. To examine the cytokine responses within the kidney, without the contribution of other organ systems, we used semi-quantitive polymerase chain reaction (RT-PCR) analysis and a recently developed kidney slice culture model from tissues of mice treated with combinations of endotoxin and neutralizing antibodies against TNF-alpha. The expression of IL-6, in addition to other pro-inflammatory cytokine genes, was increased by endotoxin treatment and reduced by pretreatment with neutralizing antibodies to TNF-alpha. Immunohistochemical staining revealed that IL-6 was expressed primarily in mesangial cells. Urinary IL-6 was also increased in endotoxin-treated mice and was inhibited by treatment with neutralizing TNF-alpha antibodies. Kinetics of the kidney-specific cytokine responses indicated that increase in TNF-alpha occurred initially, followed by IL-1 beta and finally IL-6. Furthermore, addition of TNF-alpha to glomerular mesangial cells induces IL-6 secretion. Taken together, these studies indicate that, like in the liver, a cytokine response occurs in the kidney from bacterial endotoxin and that TNF-alpha acts as a primary cytokine capable of stimulating additional cytokines, including IL-6.

Animals↗
PubMed1997

Arsenic can mediate skin neoplasia by chronic stimulation of keratinocyte-derived growth factors.

Although numerous epidemiological studies have shown that inorganic arsenicals are human skin carcinogens, there is currently no accepted mechanism for its action or an established animal model for its study. We observed increased mRNA transcripts and secretion of keratinocyte growth factors, including granulocyte macrophage-colony stimulating factor (GM-CSF) and transforming growth factor-alpha (TGF-alpha) and the proinflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) in primary human epidermal keratinocytes cultured in the presence of low micromolar concentrations of sodium arsenite. Total cell numbers, as well as c-myc expression and incorporation of [3H]thymidine, both indicators of cell proliferation, were also elevated in keratinocyte cultures treated with sodium arsenite. As an in vivo model, the influence of arsenic on mouse skin tumor development was studied in transgenic TG.AC mice which carry the v-Ha-ras oncogene, and can serve as a genetically initiated model for skin carcinogenesis. Following low-dose application of 12-O-tetradecanoyl phorbol-13-acetate (TPA), a marked increase in the number of skin papillomas occurred in transgenic mice receiving arsenic in the drinking water as compared to control drinking water. Papillomas did not develop in arsenic-treated transgenic mice that had not received TPA or arsenic-treated wild-type FVB/N mice, suggesting that arsenic is neither a tumor initiator or promoter but rather an enhancer. Injection of anti-GM-CSF antibodies following application of TPA in transgenic mice reduced the number of papillomas. Consistent with that observed in human keratinocyte cultures, increases in GM-CSF and TGF-alpha mRNA transcripts were found within the epidermis of arsenic-treated mice when compared to controls within 6 weeks of treatment. These results suggest that arsenic enhances papilloma development via the chronic stimulation of keratinocyte-derived growth factors and represents the first example of a chemical carcinogen that acts in this manner. These studies suggest that in vitro studies with human keratinocyte cultures examined in conjunction with TG.AC transgenic mice can provide a useful model for examining the tumor enhancing properties of environmental chemicals.

Animals↗
PubMed1996

Arsenic induces overexpression of growth factors in human keratinocytes.

Although epidemiological studies have shown that inorganic arsenicals are human skin carcinogens and induce hyperproliferation and hyperkeratosis, there is currently no known mechanism for their action or an established animal model for its study. We observed increased mRNA transcripts and secretion of keratinocyte growth factors, including granulocyte macrophage-colony stimulating factor (GM-CSF) and transforming growth factor-alpha (TGF alpha) and the proinflammatory cytokine tumor necrosis factor-alpha in primary human epidermal keratinocytes cultured in the presence of low micromolar concentrations of sodium arsenite. Treatment with sodium arsenite resulted in a significant increase in cell proliferation, as indicated by increases in cell numbers, c-myc gene expression, and incorporation of [3H]thymidine into cellular DNA. Studies of transcriptional regulation indicate that the rate of GM-CSF mRNA transcription is increased, while the elevated TGF alpha is likely the results of message stabilization. While a number of cytokine regulatory networks exist in the skin, studies utilizing neutralizing antibodies against the growth factors of interest indicate that inhibition of the arsenic-induced increase in TGF alpha results in a corresponding decrease in the gene expression and secretion of GM-CSF. The present studies demonstrate that growth-promoting cytokines and growth factors are induced in keratinocytes following treatment with arsenic and could play a significant role in arsenic-induced skin cancer.

Arsenites↗
PubMed1996

Indoor pollution from heating.

The concentrations of indoor pollutants generated from types of heaters were measured in a model room of 20m2 in area and 45m3 in capacity. We used six different heaters: three kerosene heaters of different types, town and propane gas heaters, and an electric heater. Three ventilation conditions were introduced into each experiment: non-ventilation, fan-on ventilation with closed door and fan-off ventilation with half-opened door. The results obtained by heating under non-ventilation condition were as follows: The concentrations of NO2 and CO2 were comparatively high and the values obtained from all the heaters except the electric heater exceeded the 1-hr Environmental Quality Standards, Japan (EQS NO2: 0.04-0.06 ppm) and the Building Sanitation Management Standards, Japan (BSMS CO2: 1,000 ppm), respectively. The CO concentration emitted from reflection kerosene and town gas heaters slightly exceeded the BSMS (10 ppm). The concentrations of suspended particulate matter and polynuclear aromatic hydrocarbons showed an increasing tendency during the use of kerosene-fueled heaters. Under two ventilating conditions, NOx concentration decreased to less than a third in comparison with non-ventilating condition.

Air Pollutants↗
PubMed1995

Role of tumor necrosis factor-alpha in cadmium-induced hepatotoxicity.

Liver and kidney injury following acute or chronic exposure to cadmium is well characterized. While hepatocytes and endothelial cells of the sinusoids are thought to be the primary cellular targets in the liver, ultrastructural changes may vary depending upon the exposure regimen and the time following administration. Since acute and chronic liver disease is often associated with the presence of cytokines, we investigated the role of proinflammatory cytokines in cadmium-induced hepatotoxicity. Supernatants from cultured liver slices obtained from acute or subchronic cadmium-exposed rats and mice were collected and cytokine secretion was examined. In addition, mRNA transcripts for IL-1 alpha, IL-1 beta, IL-6, TNF-alpha, MIP-2, IFN-gamma, and ICAM-1 from livers of treated mice were quantitated by reverse transcription-polymerase chain reaction. Modest increases in secretion of TNF-alpha, IL-1 alpha, and IL-6 were observed in response to cadmium which were enhanced in LPS-primed mice. Additionally, cadmium exposure increased IL-1 alpha, IL-1 beta, TNF-alpha, MIP-2, IL-6, and ICAM-1 mRNA transcripts in the liver. Immunohistochemical analysis revealed that TNF-alpha was associated with nonparenchymal cells in livers of cadmium-treated mice. Cadmium exposure produced a marked increase in plasma hepatocellular enzyme levels (i.e., AST, LDH, SDH), acute phase proteins (i.e., serum amyloid A), and foci formation in the liver, while focal inflammation and serum amyloid A (SAA) secretion, but not plasma enzymes, were further increased in cadmium-exposed mice primed with LPS. SAA secretion and focal inflammation were prevented by pretreatment with antibodies to TNF-alpha, indicating that these pathological manifestations are cytokine dependent. These data indicate that TNF-alpha, released from nonparenchymal cells as well as associated cytokines, are responsible for certain manifestations observed with cadmium-induced hepatotoxicity.

Animals↗
PubMed1995

Cadmium-induced renal damage and proinflammatory cytokines: possible role of IL-6 in tubular epithelial cell regeneration.

Cadmium exposure in humans and experimental animals produces renal damage characterized by degeneration and necrosis of tubular epithelial cells followed by interstitial inflammation and eventual regeneration of proximal tubular cells. Since chronic kidney diseases are often associated with the presence of inflammatory cytokines and cadmium has been reported to alter cytokine expression in monocytes and the Kupffer cells of the liver, we investigated the role of proinflammatory cytokines in cadmium-induced nephrotoxicity. Increases in TNF-alpha and IL-6 cytokine mRNA transcripts and secretion were observed in the kidney following exposure of LPS-primed mice to a total of 21 mg/kg body weight cadmium administered over a 14-week period. IL-6 was the predominant cytokine expressed and was found to be present in mesangial cells. Cadmium, in the presence of LPS, was able to induce IL-6 secretion in vitro from mouse glomerular mesangial cells. Proliferative cell nuclear antigen (PCNA) staining revealed increases in regeneration of tubular epithelial cells following cadmium exposure. Furthermore, renal tubular epithelial cells responded to IL-6 by marked proliferation. Taken together, these data suggest that cadmium-induced IL-6 secretion in the kidney may act to support the regeneration of renal tubular epithelial cells that occurs in the course of cadmium nephrotoxicity.

Animals↗
PubMed1994

[The effect of occult hyperprolactinemia (OHP) on gonadotropin secretion system].

The present study was conducted to investigate the effects of the transient increase of serum prolactin levels on the gonadotropin secretion system in patients with occult hyperprolactinemia (OHP). 216 cases of normoprolactinemic hypothalamic anovulatious were selected by LH-RH and TRH loading tests, and 5mg/day of bromocriptine was administered for more than 8 weeks. The effectiveness of the bromocriptine administration was estimated by the ultrasonic examination of the follicular development. The endocrinological backgrounds were compared between bromocriptine effective (154 cases, group A) and non-effective (62 cases, group B) patients. Serum prolactin levels 30min. after LH-RH and TRH loading (PRL30 in group A were significantly higher than those of group B (74.1 +/- 36.5 vs. 38.0 +/- 18.2ng/ml, p < 0.01). From this result, it was thought that many of the OHP patients were selected in group A. Serum LH levels 30min. after loading test (LH30) in group A also increased compared to those of group B (65.0 +/- 66.5 vs. 43.1 +/- 34.3mIU/ml, p < 0.02). The LH/FSH ratio before loading was also higher in group A (1.3 +/- 0.6) than that of group B (1.0 +/- 0.5, p < 0.02). This fact showed that group A also contained patients with hyper-LH hypothalamic anovulation, which is known as the endocrinological PCOD. There were also significant inverse correlations between serum levels of prolactin and FSH in group A (before loading values: r = 0.272, 30min. after loading: r = 0.224, p < 0.01). By the administration of bromocriptine, serum prolactin levels decreased both in group A and B, and the elevated serum LH/FSH ratio (1.0 +/- 0.4, p < = 0.02), LH30 (46.1 +/- 37.0mIU/ml, p < 0.005) also decreased significantly. Serum levels of FSH in group A increased significantly with treatment (before loading: 5.4 +/- 2.6-->6.2 +/- 2.0, 30min. after loading: 10.6 +/- 6.0-->14.6 +/- 9.9mIU/ml, p < 0.005). From these facts, it was concluded that FSH secretion was suppressed even by a slight increase of serum prolactin levels which was usually seen in the OHP, and bromocriptine administration was effective not only for the suppression of serum prolactin and LH levels, but also for the improvement of FSH secretion in the OHP patients.

Anovulation↗
PubMed1994

Cytokine induction in human epidermal keratinocytes exposed to contact irritants and its relation to chemical-induced inflammation in mouse skin.

In response to exogenous stimuli such as phorbol-12-myristate 13-acetate, ultraviolet B radiation, and lipopolysaccharide, human keratinocytes produce soluble mediators that are important in primary contact irritancy including cytokines that are associated with proinflammatory properties (interleukin-1 alpha [IL-1 alpha], tumor necrosis factor alpha), chemotaxis (IL-8), and growth activation (granulocyte/macrophage colony stimulating factor, IL-6, transforming growth factor alpha). We examined qualitative and quantitative changes in selected intracellular and secreted cytokines in human keratinocyte cultures in response to non-sensitizing contact irritants (croton oil, sodium lauryl sulfate, methyl salicylate, ethyl phenylpropiolate), sensitizing irritants (oxazolone, dinitrofluorobenzene), and ulcerative agents (phenol, benzalkonium chloride, chromium trioxide). The chemicals were also applied to mouse skin to assess whether the chemical-specific pattern of inflammation correlated with the in vitro production of keratinocyte-derived cytokines. Although all agents elicited neutrophils to the site of chemical application, time dependent and chemical-specific patterns of inflammation could be detected. Sodium lauryl sulfate, phenol, and croton oil induced increases in IL-8 production at non-cytotoxic concentrations in semi-confluent human keratinocyte cultures. Phenol and croton oil stimulated tumor necrosis factor alpha production, whereas croton oil was the only agent found to induce granulocyte/macrophage colony-stimulating factor production. Croton oil, phenol, benzalkonium chloride, and dinitrofluorobenzene induced the intracellular production of IL-1 alpha without a concomitant release into the medium. The release of cytokines occurred in parallel with a relative increase in cytokine-specific mRNA transcripts. Studies using neutralizing antibodies to tumor necrosis factor alpha and IL-1 alpha demonstrated that IL-8 induction by croton oil and phenol occurred directly rather than through autocrine circuits. These data suggest that a given pattern of cytokine production is chemical-specific and may predict the contribution of keratinocytes to skin inflammation.

Animals↗
PubMed1994

Endotoxin-induced cytokine gene expression and excretion in the liver.

Peptide mediators, including tumor necrosis factor-alpha, interleukin 1 and interleukin-6, are associated with many chronic inflammatory diseases and septic shock. As such, considerable information has been collected by means of study of cytokine secretion from isolated cells or plasma cytokines during septic shock or inflammatory disorders. In this investigation, we used semiquantitative polymerase chain reaction analysis and a recently developed liver slice model to examine the characteristics of cytokine profiles that occur in the liver, the main organ involved in endotoxemia, after lipopolysaccharide challenge. Tumor necrosis factor-alpha, interleukin-1 alpha and interleukin-6 were rapidly secreted after in vivo LPS exposure or when added in vitro to rodent or human liver slice samples. This increase was associated with increased cytokine-specific mRNA transcripts. Kinetic analysis revealed that most tumor necrosis factor-alpha is released from the liver within 1 hr of lipopolysaccharide challenge, whereas interleukin-1 alpha and interleukin-6 continued to be produced for the entire culture period. Addition of monoclonal antibodies against tumor necrosis factor-alpha or interleukin-1 alpha to the culture partly inhibited interleukin-6 secretion, indicating that interleukin-1 alpha and tumor necrosis factor-alpha help mediate and sustain interleukin-6 synthesis. Depletion of hepatic sinusoidal macrophages (Kupffer cells) by a liposome-mediated macrophage "suicide" technique indicated that almost all of the secreted interleukin-1 alpha and tumor necrosis factor-alpha originate from these cells, whereas interleukin-6 secretion might also include other cell types. This study supports and extends previous findings and allows for a more rational approach to developing effective therapies against chronic inflammatory diseases and septic shock.

Alanine Transaminase↗
PubMed1993

Effect of side-stream cigarette smoke on the hepatic cytochrome P450.

The effect of inhalation of side-stream cigarette smoke on the hepatic microsomal cytochrome P450 was investigated Rats were placed in a chamber of 0.1 m3 in volume, in which cigarettes were burned at the rate of 1, 3, or 5 cigarettes per h, 8 h/day for 5 days. Cytochrome P450 and NADPH-cytochrome c reductase showed no significant changes; however, cytochrome b5 increased significantly. On the other hand, the activity of aryl hydrocarbon hydroxylase (AHH) decreased in the rats treated with a high concentration of cigarette smoke. In order to study the changes of isoforms of cytochrome P450, western blot analyses were performed. The inductions of three kinds of isoforms, cytochromes P450IA1, IA2, and IIB1, were demonstrated immunochemically. However, there were disagreements between the results of the western blot analyses and the measurements of total cytochrome P450 content and AHH activity.

Animals↗
PubMed1993

Personal exposure to nitrogen dioxide from indoor heaters and cooking stoves.

The personal exposure to NO2 generated from various heaters and cooking stoves were studied, using 85 university students. The students attached NO2 filter badges to their chests or collars and wrote down the period of time for heating and cooking for 1 week. Types of heaters and smoking habits were described through a questionnaire. The urinary hydroxyproline/creatinine ratio (HOP/C) was examined as a biomarker for health effects. The outdoor NO2 concentration during the study period was 13.5-13.7 micrograms/m3. Smoking and the usage of electric heaters did not affect the exposure to NO2. Exposure increased according to the length of time kerosene heaters or oil fan heaters were used. The NO2 concentration during the heating by a kerosene heater and an oil fan heater was calculated to be 219 and 474 micrograms/m3, respectively. The correlation between the period of cooking and personal exposure was also observed. The NO2 levels during cooking were calculated to be 290 micrograms/m3. Using these calculated values of NO2 concentration, it is possible to presume the personal exposure levels from the length of time heaters and cooking stoves are used even if the subjects do not attach the filter badges. Neither smoking nor exposure to NO2 were associated with the increase of urinary HOP/C.

Adult↗