Smoking, alcohol drinking, green tea consumption and the risk of esophageal cancer in Japanese men

BACKGROUND: Although smoking and alcohol drinking are established risk factors of esophageal cancer, their public health impact is unclear. Furthermore, the effect of green tea is controversial. METHODS: The present study was based on a pooled analysis of two prospective cohort studies. A self-administered questionnaire about health habits was distributed to 9,008 men in Cohort 1 and 17,715 men in Cohort 2, aged 40 years or older, with no previous history of cancer. We identified 38 and 40 patient cases with esophageal cancer among the subjects in Cohort 1 (9.0 years of follow-up) and Cohort 2 (7.6 years of follow-up), respectively. Cox proportional hazards regression was used to estimate hazard ratios (HRs) of the risk of esophageal cancer incidence. RESULTS: Cigarette smoking, alcohol drinking and green tea consumption were significantly associated with an increased risk of esophageal cancer. Compared with men who had never smoked, never drunk alcohol or green tea, the pooled multivariate HRs (95% confidence intervals) were 5.09 (1.80-14.40) (p for trend <0.0001), 2.73 (1.55-4.81) (p for trend=0.0002), or 1.67 (0.89-3.16) (P for trend=0.04) for men who were currently smoking > or =20 cigarettes/day, drinking alcohol daily, or drinking > or =5 cups green tea/day, respectively. The population attributable fractions of esophageal cancer incidence that was attributable to smoking, alcohol drinking and green tea consumption were 72.0%, 48.6%, and 22.1%, respectively. CONCLUSIONS: Among the variables studied, smoking has the largest public health impact on esophageal cancer incidence in Japanese men, followed by alcohol drinking and green tea drinking.     

Alcohol consumption and lung cancer mortality in Japanese men: results from Japan collaborative cohort (JACC) study

BACKGROUND: The relationship between alcohol consumption and increased risk of lung cancer is controversial. This study was set up to investigate the association between alcohol consumption and death from lung cancer in a large Japanese cohort. METHODS: The subjects comprised 28,536 males, aged 40-79 years, living throughout Japan. During 268,464 person-years of follow-up, 377 lung cancer deaths were recorded. The hazard ratio (HR) of alcohol consumption for lung cancer mortality was calculated using the Cox proportional hazards model after adjustment for age, smoking and family history of lung cancer. RESULTS: There was no association between increased mortality from lung cancer and alcohol consumption among current drinkers. Compared with subjects who had never drunk alcohol, the HRs (95% confidence interval [CI]) of death from lung cancer for light (consuming <25.0 g ethanol per day), moderate (25.0-49.9 g per day) and heavy (>or=50 g per day) drinkers were 0.81 (95% CI=0.61-1.07), 0.82 (0.61-1.11) and 0.97 (0.66-1.43), respectively. Further adjustment for fruit and vegetable intake did not change the results, and there was no change in HR materially after excluding those patients who died during the first 5 years of follow-up. CONCLUSIONS: These findings indicate that alcohol consumption was not associated with increased lung cancer mortality in this population of Japanese men.     

Surgical outcome of stentless aortic valve replacement for calcified aortic stenosis

We have conducted aortic valve replacement (AVR) using a stentless bioprosthesis (Medtronic Freestyle valve) on 10 patients with calcified aortic stenosis since March 2004. There were 64-84 years of age and 75 ± 5.5 years old on average, and included 4 males. Implantation was conducted by a modified subcoronary method in all the patients. The preoperative New York Heart Association class was class II in 80% of the patients. The preoperative left ventricular mass and the left ventricular mass index (LVMI) were 193.1-524.1 g and 144.1-299.5 g/m2 and, on average 328.4 ± 104.7 g and 217.3 ± 55.7 g/m2, respectively. The annulus dimension was 18-24 mm and, on average, 20.3 ± 1.7 mm. The size of implanted valve was 19-25 mm and, on average, 21 ± 2.2 mm. The maximum pressure gradient of the aortic valve remained at 14.2-46.5 mmHg, 25.2 ± 10.2 mmHg on average, 1 or 2 months after surgery, but the LVMI significantly improved to 153.2 ± 33.9 g/m2 (p = 0.018). The hospitalization period were 24.7 ± 16.9 days for all the patients and 19.3 ± 5.1 days for patients undergoing the AVR alone. These results show that LVMI is significantly reduced by using a stentless bioprosthesis in the early phase after surgery, and early discharge from hospital can be expected by concurrently using minimally invasive cardiac surgery.     

Characterization of an immortalized hepatic stellate cell line established from metallothionein-null mice

Hepatic stellate (HS) cells were isolated from the livers of metallothionein (MT)-null and control mice and used to establish IMS/MT(-) and IMS/N cell lines, respectively, using SV40 virus transformation. Cellular morphology, incorporation of vitamin A and expression of alpha-SMA, desmin and SV40 T-antigen were used to confirm that both cell lines were immortal HS cells. The growth rates of both cell lines were similar and there was little difference between cell line sensitivity to zinc. MT-null IMS/MT(-) cells were more sensitive to cadmium and mercury, although both cell lines accumulated almost equal amounts of cadmium during a 24-hr culture period. As HS cells play an important role in hepatic fibrosis and are activated by heavy metals such as cadmium or reactive oxygen, the MT-null HS cell line derived in this study should be a useful experimental model for examination of the role of MT in HS cell activation.     

Active oxygen processing for acrylic intraocular lenses to prevent posterior capsule opacification

PURPOSE: To evaluate active oxygen processing on the surface of acrylic intraocular lenses (IOLs) to prevent secondary posterior capsule opacification (PCO). SETTING: Department of Ophthalmology, Dokkyo Medical University School of Medicine, Mibu City, Tochigi, Japan. METHODS: Acrylic IOLs were prepared, and ultraviolet (UV)/ozone (UV/O3) or argon plasma was irradiated to the surface of the IOLs. Elemental analysis (electron spectroscopy for chemical analysis [ESCA]) of the IOL surfaces was performed to confirm surface modification. Changes produced by UV/O3 or argon plasma treatment were examined for fibronectin and lens epithelial cell (LEC) adhesion. To evaluate the PCO prevention by treated IOLs, 8-week-old albino rabbits were used. The rabbit eyes randomly had phacoemulcification and implantation of 3 different IOLs: the UV/O3-treated IOLs, argon plasma-treated IOLs, and the control IOLs. After 2 weeks, the rabbits were killed and their globes were dissected and fixed using formaldehyde 10%. The PCO was observed using light microscopy (DX51, ORIMPUS) after hematoxylin and eosin staining. RESULTS: Comparison of IOL surface composition by ESCA showed an increase in nitrogen content and hydroxyl substitute and carboxyl substitute groups on surfaces of treated IOLs. The fibronectin adhesion and the LEC adhesion on the UV/O3-treated and argon plasma-treated samples were increased. In the untreated group, there was statistically significant inhibition of PCO formation in the UV/O3-treated and argon plasma-treated groups. CONCLUSION: Active oxygen processing and argon plasma irradiation on the surface of IOLs was effective in preventing secondary PCO after cataract surgery.     

TYROSINEMIA

A case of tyrosinemia in a three-month-old boy is presented. The patient appeared jaundiced initially with markedly elevated levels of serum tyrosine and a positive Millon-reacting urine. Jaundice persisted and hepatospleno-megaly gradually increased. He died due to liver failure on the 51st day after admission. At autopsy, the liver showed the features of severe giant cell hepatitis including giant cell formation, fibrosis and bile retention. The pancreas and the brain showed characteristic postmortem Andings as previously reported in patients with tyrosinemia. ACTA PATH. JAP. 29: 615–622, 1979.     

Therapeutic effects for hypersensitivity pneumonitis induced by Japanese mushroom (Bunashimeji)

BACKGROUND: Bunashimeji-related hypersensitivity pneumonitis is found among workers who cultivate the mushroom in indoor facilities. An evaluation of protective measures was initiated using the outcomes of clinical, immunological, and radiological findings. METHODS: Twenty-two patients presented with symptoms of HP; all were employed cultivating Bunashimeji mushrooms in indoor facilities. After hospitalization, 6 of 22 patients quit their job to avoid exposure to spores (Avoidance group). Sixteen patients continued to work used a mask for 3 months, and were then divided into two subgroups: Mask alone (seven patients) and mask plus oral prednisolone (Mask + PSL) (nine patients). The erythrocyte sedimentation rate (ESR), serum Krebs von der Lungen-6 (KL-6), surfactant protein-D (SP-D), lymphocyte stimulation test (LST), ground-glass scores in chest high-resolution computed tomography (HRCT), and bronchoalveolar lavage (BAL) were assessed before and after treatment. RESULTS: Complete avoidance resulted in a significant decrease in LST. There was a significant decrease after PSL treatment in serum KL-6, SP-D, and total cell counts in the BAL fluid in the Mask + PSL group. In the Mask alone group, serum KL-6, SP-D, ground-glass scores in chest HRCT and total cell counts in BAL fluid showed high levels compared with the other two groups. CONCLUSIONS: Complete cessation was the best treatment for hypersensitivity pneumonitis. The use of a mask was ineffective for patients with a high serum KL-6 and SP-D concentration and severe ground-glass opacity on chest HRCT. Initial treatment with PSL is recommended for these patients with high levels of total cell counts in BAL fluid.     

Treatment of Eyelid Epithelial Neoplasm by Targeting Sonic Hedgehog Signaling: An Experimental Study

Purpose

To evaluate the effect of cyclopamine, an inhibitor of the Sonic hedgehog (Shh) signal, on the growth of an epithelial neoplasm.

Methods

Chemically induced eyelid tumors in XPC-null mice (n = 40) were treated daily with a subcutaneous injection of cyclopamine (1?mg/animal) for 7 days. The animals were killed after bromodeoxyuridine (BrdU) labeling, and the tumors were histologically examined. An in vitro study was conducted by using a squamous cell carcinoma (SCC) cell line. The SCC cells were treated with 0, 12.5, or 25.0?μg/ml recombinant Shh (rShh) and either 0 or 100?μM cyclopamine, and cell proliferation was evaluated by using an MTT assay. Cells from this cell line were also implanted subcutaneously in nude mice (n = 8) to develop tumors, and the effect of cyclopamine administration was examined in the developed tumors.

Results

Histology showed that cyclopamine treatment suppressed BrdU incorporation and induced apoptosis in the majority of cells in tumors chemically induced in the eyelid of the XPC-null mice. Cell proliferation of the SCC cell line was enhanced by adding rShh, and this effect was abolished by adding cyclopamine. Proliferation of the SCC cell line was not affected by adding cyclopamine in the absence of rShh. On the other hand, the SCC cells expressed Shh in vivo in tumors developed in nude mice, but cyclopamine suppressed cell proliferation in the tumors, and the Shh-signaling pathway was inhibited by cyclopamine-induced apoptosis.

Conclusions

Cyclopamine inhibits proliferation and induces apoptosis in epithelial tumor cells in vivo. The Shh-signaling pathway may be a potential therapeutic target for patients with eyelid tumors.?Jpn J Ophthalmol 2006;50:305–311 © Japanese Ophthalmological Society 2006     

Genipin suppresses subconjunctival fibroblast migration, proliferation and myofibroblast transdifferentiation

PURPOSE: Inchin-ko-to is a herbal medicine which has therapeutic effects in ameliorating liver fibrosis or cholestatic liver diseases. Its main bioactive component is genipin, which is an intestinal bacterial metabolite of this medication. Accordingly, we determined whether or not Inchin-ko-to suppresses in a wound healing model subconjunctival fibroblast (SCF) migration proliferation and myofibroblast transdifferentiation since an inhibitory effect could be of value in improving trabeculotomy outcome. METHODS: Effects of genipin on SCF cell migration were examined subsequent to wounding confluent monolayer cultures. Alamar blue staining evaluated the effects of genipin (0-50 microg/ml) on fibroblast cell proliferation. Immunostaining determined alpha-smooth muscle actin (alphaSMA) expression. Western blotting evaluated (alphaSMA) expression and phospho-Smad2 formation. Real-time RT-PCR evaluated TGFbeta1 and collagen Ialpha2 mRNA expression. Enzyme-immunoassay determined culture medium collagen I content. RESULTS: Genipin suppressed wound-induced cell migration and proliferation. It also decreased collagen type I TGFbeta1 and alphaSMA mRNA and protein expression. Smad2 signaling was inhibited by genipin in a dose-dependent manner. CONCLUSION: Genipin suppresses injury-induced fibrogenic responses in SCFs. This result suggests that the herbal medicine Inchin-ko-to might have therapeutic value following trabeculotomy.