Source efficiency of alpha-emitters applied to the skin surface.

Skin surface contamination by alpha-emitters is in itself not hazardous, but it would cause significant internal exposure in the case of injured skin as well as misjudgment in direct in vivo measurements (e.g. lung counting). The present study determined the source efficiency of alpha-emitters (241Am) applied to swine skin samples by analysing the observed alpha-particle energy spectra using advanced alpha-spectrometric simulation. Based on our results, the source efficiency was determined to be 0.365 (alpha-particle s-1 per Bq) on average (c.f. 0.5 in the case of no self-absorption in the source). The decrease in source efficiency would be attributed primarily to the radionuclide entering hair follicles or deep wrinkles. The degradation of the measured spectra from the skin samples indicates the penetration of some radionuclides into the upper layers of the stratum corneum. Although this study was limited to results obtained from swine skin samples, it suggests that irregularities in the skin surface may affect direct alpha measurements.

Facilitation of bone resorption activities in synovial lavage fluid patients with mandibular condyle fractures.

The aim of this study was to investigate the bone resorption effect of the mediators delivered in joint cavity of patients with mandibular condyle fractures by detecting osteoclast markers using cellular biochemistry methods, and by analysing bone resorption activities via inducing osteoclast differentiation of the infiltrated cells from arthrocentesis. Sixteen joints in 10 patients with mandibular condyle fractures were evaluated. The control group consisted of synovial fluid (SF) samples from seven joints of four volunteers who had no clinical signs or symptoms involving the temporomandibular joint (TMJ) or disc displacement. We collected SF cells from all patients during therapeutic arthrocentesis. The infiltrating cells from TMJ SF were cultured, differentiated into tartrate-resistant acid phosphatase (TRAP)-positive osteoclast-like cells and examined bone resorption activities. We also investigated factors related to osteoclast induction of SF, using ELISA procedures. Osteoclast-like cells were induced from the SF cells obtained from all patients with condylar fractures. These multinucleated giant cells were positive for TRAP and actin, and had the ability to absorb dentin slices. The levels of macrophage colony-stimulating factor (M-CSF), prostaglandin E2 (PGE2), soluble form of receptor activator of nuclear factor kappa-B ligand (sRANKL) and osteoprotegerin (OPG), in SF samples from the patients, were significantly higher than in the controls. These findings indicate that bone resorption activities in SF from patients with mandibular condyle fractures were upregulated and may participate in the pathogenesis and wound healing.

EFFECT OF SEASONAL CHANGES ON TESTICULAR MORPHOLOGY AND THE EXPRESSION OF CIRCADIAN CLOCK GENES IN JAPANESE WOOD MICE (APODEMUS SPECIOSUS).

This study aimed to determine the seasonality of reproduction throughout the year in Japanese wood mice (Apodemus speciosus). The effect of seasonal changes on testicular morphology and the periodic expression of circadian clock genes in the hypothalamus and testes of male individuals was evaluated. We also examined the morphology of the testes and caudae epididymides of male mice. In addition, RT-PCR analysis was carried out with mRNA extracted from the hypothalamus and testes to evaluate the expression of the circadian clock genes Clock, Bmal1, Per1, and Cry1. The complete induction of testicular activity was detected from February to April and from August to October, with testes weight increasing with the completion of spermatogenesis (reproductive season). From May to early June and from November to early January, testicular weight declined, the seminiferous tubules reduced in size, spermatogenesis was arrested, and sperm were not produced (non-reproductive season). From mid- June to July and mid-January, the re-induction of testicular activity for spermatogenesis was observed in the seminiferous tubules (transitional season). Out of the four examined genes, Cry1 had the highest expression level in both the hypothalamus and testes throughout the year, followed by Bmal1, Per1, and Clock. The expression of Bmal1 was significantly lower in the hypothalamus and testes during the transitional season compared to the reproductive and non-reproductive seasons. Cry1 transcript levels were also significantly lower in the hypothalamus and testes during the transitional season compared to the reproductive season. In conclusion, the results indicating changes in testicular morphology revealed annual reproductive, non-reproductive, and transmission periods in Japanese wood mice. When an increase in testicular activity was observed indicating the onset of the reproductive season, the mean day length was approximately 11–13 h. The expression of the circadian clock genes Bmal1 and Cry1 in the hypothalamus and testes during the reproductive season was significantly higher than that of the same genes during the transitional season. Consequently, completion of spermatogenesis occurred in the seminiferous tubules of Japanese wood mice testes during the reproductive period.

How do employment types and job stressors relate to occupational injury? A cross-sectional investigation of employees in Japan.

OBJECTIVE: This study investigated whether 1) the risk of occupational injury differs among permanent employees and specific types of temporary workers, 2) the risk of occupational injury differs across different employment types depending on the degree of job stressors. STUDY DESIGN: A cross-sectional study design based on self-report survey data. METHODS: A total of 36,688 full-time workers (28,868 men and 7820 women; average age = 35.4) were surveyed by means of a self-administered questionnaire. Employment types consisted of permanent employment and two forms of temporary employment: direct-hire and temporary work agent (TWA). Job characteristics including job demands, job control, and social support at work were measured. Occupational injury was measured by asking whether the participant had an injury on the job in the past 12 months that required a medical treatment. To investigate the relationships between employment types, job stressors, and occupational injury, hierarchical moderated logistic regression tests were conducted. RESULTS: High job demands (OR = 1.44) and low job control (OR = 1.21) were significantly associated with an increased risk of occupational injury, while controlling for demographic, life style, health, and occupational factors. In addition, direct-hires (OR = 1.85) and temporary agent workers (OR = 3.26) had a higher risk of occupational injury compared with permanent employees. However, the relationship between employment types and the risk of occupational injury depended on the levels of job demands and job control. Specifically, the magnitude of the relationship between job demands and the risk of occupational injury was substantially greater for temporary work agents than for permanent employees when they reported low levels of job control. Such an interaction effect between job demands and job control on the risk of occupational injury was not observed between permanent employees and direct-hire temporary workers. CONCLUSION: The current study indicated that temporary workers might be more vulnerable to occupational injury than permanent employees. High levels of job demands and low levels of job control might also add to temporary workers' risk of occupational injury, particularly for TWAs.

Radioactive pollution from Fukushima Daiichi nuclear power plant in the terrestrial environment.

Major contaminants from venting and hydrogen explosions at the Fukushima Daiichi nuclear reactors between 12 and 15 March 2011 were transported northwestward and deposited on soil and plants via precipitation. Surface soils and plant leaves were sampled at 64 sites in the Fukushima Prefecture. The highest concentrations of (134)Cs (84.4 kBq kg(-1)) and (137)Cs (82.0 kBq kg(-1)) in surface soils were observed at Nagadoro in Iidate village located 32 km northwest from the Fukushima Daiichi nuclear power plant. Furthermore, (131)I, (129)Te, (129 m)Te, (110 m)Ag and (140)La were detected in the same samples. Outer surface of plant leaves, such as bamboo, cabbage and grasses were highly contaminated at the high-dose rate areas of Tsushima and Minami-Tsushima in Namie town. Mugwort leaves that grew after the pollution event had extremely low concentration of radionuclides; however, the plant/soil radiocaesium ratio was 0.023 ± 0.006. It is anticipated that decomposition of fallen leaves will promote recycling of radionuclides in the environment.

Extended-spectrum ß-lactamase-producing Escherichia coli strains in the feces of carriers contribute substantially to urinary tract infections in these patients.

INTRODUCTION: The current increase in the incidence of urinary tract infections (UTIs) worldwide caused by extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli may be due to the high number of ESBL-producing Enterobacteriaceae carriers in the community. However, whether ESBL-producing bacteria can cause UTIs in carriers remains uncertain. MATERIALS AND METHODS: In this study, 21 fecal carriers of ESBL-producing Enterobacteriaceae were assessed for UTIs caused by ESBL-producing E. coli. Bacterial isolates obtained from patients' urine and stool specimens were phenotypically and genotypically examined. Clonal similarities of isolates were assessed by multilocus sequence typing (MLST) and random amplified polymorphic DNA (RAPD) fingerprinting. RESULTS: The study revealed that 9 of 21 carriers developed UTIs, and genetic analysis showed that 44% of the UTIs developed were caused by the same ESBL-producing E. coli as that found in the feces of the patients. CONCLUSIONS: The ESBL-producing E. coli in carriers can cause UTIs.

Active cigarette smoking, secondhand smoke exposure at work and home, and self-rated health.

OBJECTIVES: Although active smoking has been reported to be associated with poor self-rated health (SRH), its association with secondhand smoke (SHS) is not well understood. STUDY DESIGN: A cross-sectional study was conducted to examine the association of active smoking and SHS exposure with SRH. METHODS: A total of 2558 workers (1899 men and 689 women), aged 16-83 (mean 45) years, in 296 small and medium-sized enterprises were surveyed by means of a self-administered questionnaire. Smoking status and exposure levels to SHS (no, occasional or regular) among lifetime non-smokers were assessed separately at work and at home. SRH was assessed with the question: How would you describe your health during the past 1-year period (very poor, poor, good, very good)? SRH was dichotomized into suboptimal (poor, very poor) and optimal (good, very good). Odds ratios (ORs) with 95% confidence intervals (CIs) for reporting suboptimal vs optimal SRH according to smoking status and smoke exposure were calculated. RESULTS: Current heavy smokers (20+ cigarettes/day) had a significantly increased suboptimal SRH than lifetime non-smokers after adjusting for sociodemographic, lifestyle, physical and occupational factors (OR 1.34, 95% CI 1.06-1.69). Similarly, lifetime non-smokers occasionally exposed to SHS at work alone had worse SRH than their unexposed counterparts (OR 1.50, 95% CI 1.02-2.11). In contrast, lifetime non-smokers exposed at home alone had no significant increase in suboptimal SRH. CONCLUSIONS: The present study indicates an increase in suboptimal SRH among current heavy smokers, and suggests that SHS exposure at work is a possible risk factor for non-smokers. Whether or not the association is causal, control of smoking at work may protect workers from developing future health conditions.

Evaluation of the position, mobility, and morphology of the disc by MRI before and after four different treatments for temporomandibular joint disorders.

OBJECTIVES: The purpose of this study was to evaluate changes in disc position, mobility, and morphology in patients with temporomandibular joint disorders (TMD) in response to four different treatments, splint therapy, pumping manipulation, arthrocentesis, and arthroscopic surgery, using magnetic resonance imaging (MRI). METHODS: Eighty-five joints (85 patients) with unilateral internal derangement or osteoarthritis that were successfully treated were included in this study. The patients were divided into four groups as follows: splint therapy group, pumping manipulation group, arthrocentesis group, and arthroscopic surgery group. Changes in the disc position, mobility, and morphology before and after treatment were compared among the four groups using MRI. RESULTS: All discs showed anterior disc displacement (ADD) without reduction before treatment. Only 10% of the joints became ADD with reduction after treatment, and the other joints remained ADD without reduction in spite of treatment. Discs treated by arthroscopic surgery were located more anteriorly compared with pre-treatment. In pre-treatment MRI, the rate of stuck disc increased as the stage of the treatment advanced. In post-treatment MRI, all temporomandibular joints (TMJs) had mobile discs. The disc deformity advanced after arthrocentesis and arthroscopic surgery. CONCLUSIONS: Even though clinical signs and symptoms were alleviated by treatment, most discs remained ADD without reduction on MRI in spite of treatment. This suggests that the four treatments do not necessarily improve the position and deformity of the disc, and that arthroscopic surgery advances the deformity and anterior displacement of the disc. Disc mobility is important for improving clinical signs and symptoms.

The characteristics of karyotype and telomeric satellite DNA sequences in the cricket, Gryllus bimaculatus (Orthoptera, Gryllidae).

The chromosomes derived from the Japanese population of Gryllus bimaculatus were characterized by C-banding and Ag-NOR staining. The chromosome number, 2n = 28 + XX (female)/XO (male), corresponded with that of other populations of G. bimaculatus, but the chromosome configuration in idiograms varied between the populations. NORs were carried on one pair of autosomes and appeared polymorphous. The positive C-bands located at the centromere of all chromosomes and the distal regions of many chromosome pairs, and the size and the distribution pattern of the distal C-heterochromatin showed differences among the chromosomes. In addition, this paper reports on the characteristics of HindIII satellite DNA isolated from the genome of G. bimaculatus. The HindIII repetitive fragments were about 0.54 kb long, and localized at the distal C-bands of the autosomes and the interstitial C-bands of the X chromosome. Molecular analysis showed two distinct satellite DNA sequences, named the GBH535 and GBH542 families, with high AT contents of about 67 and 66%, respectively. The two repetitive families seem to be derived from a common ancestral sequence, and both families possessed the same 13-bp palindrome sequence. The results of Southern blot hybridization suggest that the sequence of the GBH535 family is conserved in the genomic DNAs of Gryllus species, whereas the GBH542 family is a species-specific sequence.

Isolation and characterization of synovial cells from the human temporomandibular joint.

BACKGROUND: The synovial tissues with temporomandibular disorders (TMDs) often show chronic inflammatory changes and the synovial cells participate in the pathogenic processes of TMDs. The synovial membrane is composed of a synovial lining layer and a connective sublining layer. The synovial lining layer is made up of two kinds of cells: macrophage-like type A and fibroblastic type B cells. The aim of this study was to isolate and characterize synovial cells from the human temporomandibular joint (TMJ). METHODS: Synovial cells were isolated using an explant culture method. Then, we characterized the cultured synovial cells (SGA2 cells) using immunocytochemistry. RESULTS: SGA2 cells expressed the fibroblastic markers vimentin and prolyl 4-hydroxylase; they also expressed laminin and heat shock protein 27, all of which are markers of type B cells. However, some cells expressed the macrophage marker CD68. These CD68-positive cells simultaneously expressed laminin. CONCLUSIONS: We isolated and cultured synovial type B cells from the human TMJ, and identified the presence of intermediate type synovial lining cells, having the phenotypic properties of both type A and type B cells, among the synovial lining cells.

Molecular cytogenetic characterization and chromosomal distribution of the satellite DNA in the genome of Oxya hyla intricata (Orthoptera: Catantopidae).

The genomic DNA of the grasshopper (Oxya hyla intricata) was subjected to electrophoresis after digestion with HaeIII, and the result showed two bands of highly repetitive DNA, approximately 200 and 400 bp in length. The 200-bp HaeIII-digested fragment was cloned and characterized by sequencing and fluorescence in situ hybridization (FISH). The results showed the presence of two distinct satellite DNA (stDNA) families: one consisting of a 169-bp repeated element having an A+T content of 60.9% and the other consisting of a 204-bp repeated element having an A+T content of 53.9%. No significant homology between the two stDNA families was observed. FISH showed that the chromosomal locations of these families are different from each other. The 169-bp element was located in the C-band-positive regions of the short arms of most of the chromosomes, whereas the 204-bp element was located in the centromeric regions of three chromosome pairs. These results imply that the origins of these two DNA families are different. The results of zoo-blot hybridization to the genomic DNA from four Oxya species, O. hyla intricata, O. japonica japonica, O. chinensis formosana, and O. yezoensis, suggest that the two stDNA families found in the present study are species-specific for O. hyla intricata.

Karyotypic evolution and organization of the highly repetitive DNA sequences in the Japanese shrew-moles, Dymecodon pilirostris and Urotrichus talpoides.

The karyological relationship and organization of highly repetitive DNA sequences in Japanese shrew-moles were studied by zoo-blot hybridization and fluorescence in situ hybridization (FISH). When the genomic DNA of the eastern race of Urotrichus talpoides was digested with PstI, three fragments of highly repetitive DNA sequences, approximately 0.7, 0.9, and 1.4 kb in length, were observed as distinct bands. The results of FISH in the eastern race of U. talpoides using these three fragments separately as probes showed that the 0.7-kb PstI fragment was distributed in the centromeric regions of most chromosomes, and that the 0.9- and 1.4-kb fragments were predominantly located in the C-heterochromatin region of chromosome 13p. Although the western race of U. talpoides also had three PstI fragments, 0.9- and 1.4-kb PstI fragments were more ambiguous than those of the eastern race. The PstI- digested genomic DNA in Dymecodonpilirostris produced only a faint 0.9-kb band, and its signal patterns obtained by zoo-blot hybridization were clearly different from those of U. talpoides. The 0.7-kb fragment of U. talpoides hybridized strongly with the 0.9-kb fragment of D. pilirostris. In a FISH analysis, the 0.9-kb fragment of D. pilirostris hybridized with highly repetitive DNA in the centromeric regions of most chromosomes from both D. pilirostris and U. talpoides. Zoo-blot hybridization and FISH analyses suggest that the 0.9- and 1.4-kb PstI fragments were generated specifically in the genome of U. talpoides after the common ancestor differentiated into two extant shrew-mole species. A difference in the length of the centromeric elements between U. talpoides and D. pilirostris might be observed due to certain modifications of the repeating unit.

Naïve (CD4+CD45RA+) T cell subpopulation is susceptible to various types of hazardous substances in the workplace.

To find the most susceptible lymphocyte subpopulation with exposure to various occupational hazardous substances, we reanalyzed our previous data. We measured T, B and natural killer NK cell subpopulations by means of flowcytometry among workers who were exposed to aromatic amines, chromate, mercury lead and organic-solvents. The exposed/non-exposed ratio was defined as the mean value of the absolute number of lymphocyte subpopulations in the exposed workers divided by the corresponding value of the non-exposed control group in 5 studies reported previously by us. The ratio of CD4+CD45RA+ T cells in all the exposed groups examined in this study was less than 1.0, and the mean of these ratio was 0.77, which was the lowest among lymphocyte subpopulations examined. The mean ratio was 1.06 for CD4+CD29+ T cells, 0.91 for CD4+ T cells, 0.99 for CD8+ T cells, 0.93 for CD3+ T cells, 0.99 for CD19+B cells, 0.96 for CD57-CD16+ NK cells, 0.82 for CD57+CD16+ NK cells, 1.25 for CD57+CD16- NK cells and 0.89 for total lymphocytes. With regard to the difference between exposed and non-exposed workers the estimated overall difference in the mean absolute number of CD4+CD45RA+ T cell subpopulation between exposed and non-exposed workers among five studies was -135 ((% confidence interval, CI: (-194,-75)) cells/mm3 (p<0.01). In conclusion, naïve (CD4+CD45RA+) T cell subpopulation was the most susceptible to the effects of various toxic substances as compared with other lymphocyte subpopulations. This lympohocyte subpopulation may be useful for monitoring immune system of workers exposed to various types of substances in the workplace.

Theoretical study on the excited states of psoralen compounds bonded to a thymine residue.

Time-dependent density functional theory calculations have been performed for the excited states of psoralen, 5-methoxypsoralen, and 8-methoxypsoralen in systems and furan and pyrone monoadducts bonded to a thymine residue. The theoretical assignments to ultraviolet (UV) absorption spectra of isolated systems have been performed. The present calculations have clarified that the excitation energies of the first singlet excited (S1) state of monoadducts are blue-shifted compared with the isolated systems. It is shown that, in particular, the S1 excitation energy of the pyrone monoadduct is significantly blue-shifted and, therefore, the pyrone monoadduct is not excited by UV-A light (300-400 nm), which is used in the photochemotherapy.

Potential role of phosphodiesterase 7 in human T cell function: comparative effects of two phosphodiesterase inhibitors.

Even though the existence of phosphodiesterase (PDE) 7 in T cells has been proved, the lack of a selective PDE7 inhibitor has confounded an accurate assessment of PDE7 function in such cells. In order to elucidate the role of PDE7 in human T cell function, the effects of two PDE inhibitors on PDE7A activity, cytokine synthesis, proliferation and CD25 expression of human peripheral blood mononuclear cells (PBMC) were determined. Recombinant human PDE7A was obtained and subjected to cyclic AMP-hydrolysis assay. PBMC of Dermatophagoides farinae mite extract (Df)-sensitive donors were stimulated with the relevant antigen or an anti-CD3 monoclonal antibody (MoAb). PBMC produced IL-5 and proliferated in response to stimulation with Df, while stimulation with anti-CD3 MoAb induced CD25 expression and messenger RNA (mRNA) synthesis of IL-2, IL-4 and IL-5 in peripheral T cells. A PDE inhibitor, T-2585, which suppressed PDE4 isoenzyme with high potency (IC50 = 0.00013 microM) and PDE7A with low potency (IC50 = 1.7 microM) inhibited cytokine synthesis, proliferation and CD25 expression in the dose range at which the drug suppressed PDE7A activity. A potent selective inhibitor of PDE4 (IC50 = 0.00031 microM), RP 73401, which did not effectively suppress PDE7A (IC50 > 10 microM), inhibited the Df- and anti-CD3 MoAb-stimulated responses only weakly, even at 10 microM. PDE7 may play a critical role in the regulation of human T cell function, and thereby selective PDE7 inhibitors have the potential to be used to treat immunological and inflammatory disorders.

Transient contribution of mast cells to pulmonary eosinophilia but not to hyper-responsiveness.

BACKGROUND: We have recently demonstrated that the transfer of interleukin (IL)-5-producing CD4+ T cell clones into unprimed mice is sufficient for the development ofeosinophilic inflammation in the bronchial mucosa upon antigen inhalation. OBJECTIVE: The aim of this study was to elucidate the possible contribution of mast cells in eosinophilic inflammation and bronchial hyper-responsiveness (BHR), and to discriminate between the roles of CD4+ T cells and mast cells. METHODS: Mast cell-deficient mice (WBB6F1-W/Wv) and their congenic normal littermates (WBB6F1-+/+) were immunized with ovalbumin and challenged by inhalation with the relevant antigen. RESULTS: Airway eosinophilia was induced with equivalent intensity in +/+ and W/Wv mice 6, 24, 96 and 216 h after antigen inhalation. In contrast, 48 h after antigen challenge, eosinophilic infiltration into the bronchial mucosa was significantly less pronounced in W/Wv mice than in +/+ mice. Anti-CD4 monoclonal antibody (mAb), anti-IL-5 mAb, and cyclosporin A were administered next, demonstrating that the airway eosinophilia of W/Wv mice induced 48 h after antigen challenge was almost completely inhibited by each of these three treatments, but that of +/+ mice was significantly less susceptible. Bronchial responsiveness to acetylcholine was increased 48 h after antigen challenge and was not significantly different between +/+ and W/Wv mice. Administration of anti-IL-5 mAb completely inhibited the development of BHR in both +/+ and W/Wv mice. CONCLUSION: These results indicate that, in mice, mast cells do have a supplemental role in the development of pulmonary eosinophilia but not BHR. CD4+ T cells totally regulate these responses by producing IL-5.

Dynamics of antigen-specific helper T cells at the initiation of airway eosinophilic inflammation.

Bronchial asthma is characterized by chronic eosinophilic inflammation of the bronchial mucosa in which Th2 cells play crucial roles. Ovalbumin-reactive Th2 clones were labeled with a fluorescent-probe then infused into unprimed mice to elucidate the dynamics of antigen-specific T cells involved in allergic inflammation. Infiltration of not only labeled antigen-specific T cells, but also unlabeled nonspecific CD4(+) T cells into the bronchial mucosa following inhaled antigen challenge was detectable under confocal microscopy and flow cytometry. Accordingly, labeled T cells in the spleen were decreased, whereas those in hilar lymph nodes were increased upon antigen challenge. Approximately 45% of antigen-specific T cells that migrated into the lungs bore CD25, while another early activation marker, CD69, was expressed on 80% of the migrated T cells. Accordingly, antigen challenge to the mice induced in situ proliferation of antigen-specific T cells as well as bronchial epithelial cells in the lungs. Expression of vascular cell adhesion molecule (VCAM)-1, but not intercellular adhesion molecule (ICAM)-1, on the vascular endothelium in the lungs was enhanced following antigen challenge. Nevertheless, treatment with anti-VCAM-1 antibody, and also anti-ICAM-1 antibody strongly suppressed the accumulation of T cells, suggesting that both VCAM-1 and ICAM-1 are essential for antigen-stimulated T cell mobilization into peripheral tissues. Our current study visualized the kinetics and the mechanism of antigen-specific T cell migration in response to local challenge with a protein antigen.

Immunohistochemical localization of Betacellulin, a member of epidermal growth factor family, in atherosclerotic plaques of human aorta.

Betacellulin (BTC), a new member of the EGF family, has been reported to be a potent mitogen for rat vascular smooth muscle cells (SMCs). BTC mRNA is known to be expressed in several human organs. However, the localization of BTC in human vascular tissues has not yet been clarified. We investigated whether or not BTC protein is involved in the pathogenesis of human atherosclerosis. Recombinant human BTC showed a mitogenic activity on cultured human aortic SMCs by measuring [3H]thymidine incorporation. The immunohistochemical localization of BTC, SMCs, macrophages, EGF receptors and ErbB4 was examined in autopsied human aortas. BTC was detected in both intimal and medial SMCs of the aortic wall. The percentage of BTC-positive medial SMCs in early types of atherosclerotic lesions decreased with age, but in adult, it was significantly higher in advanced types than in early types of atherosclerotic lesions. BTC-positive SMCs were predominantly localized in the medial side of the intima. Furthermore, numerous BTC-positive SMCs and macrophages were observed around the core lesion of atherosclerotic plaques. Receptors for BTC, EGF receptor and ErbB4, were expressed on SMCs, suggesting that BTC is associated with EGF receptor family-mediated signaling. BTC is produced in human aortic tissue and might play important roles in atherogenesis.