HLA‐C*12:02 is a susceptibility factor in late‐onset type of psoriasis in Japanese

Psoriasis is thought to be a multifactorial disease triggered by both genetic and environmental factors. The HLA‐C locus on chromosome 6p21.33 remains the strongest susceptibility candidate locus in psoriasis. The strong association between psoriasis and the HLA‐Cw6 allele has been well documented in various races. It is known that psoriatic patients with early onset are more likely to be familial and associated with HLA‐Cw6. Familial occurrence of Japanese psoriasis is smaller than other populations. Furthermore, males are predominant over females in Japanese psoriasis. We investigated the relation between HLA‐C alleles and age of onset, and in each gender for Japanese psoriasis, and discuss male predominance in the incidence of psoriasis in Japan. Four hundred forty six unrelated Japanese patients with psoriasis vulgaris and 557 sex‐ and age‐matched unrelated Japanese healthy controls were investigated by genotyping. We confirmed the association between early‐onset type of psoriasis with HLA‐C*06:02 allele in Japanese. In addition, we detected the association between the late‐onset type of psoriasis and the HLA‐C*12:02 allele in Japanese. No significant differences in allele frequency were observed between females and males. Our results suggest that there is no genetic factor effect on male predominance in Japanese. In contract, the effect of environmental risk factors on the onset of Japanese psoriatic patients is stronger in males than in females. As a result, male predominant in psoriasis may occur in Japan.     

Cigarette smoking and subsequent risk of lung cancer by histologic type in middle-aged Japanese men and women: the JPHC study

In order to update the findings of relative risk associated with cigarette smoking for lung cancer by histologic type in Japan, the data from a population-based cohort study of 91,738 men and women were analyzed. During 1990-1999, 422 lung cancer incident cases were identified. The relative risk for all incident cases associated with current smokers versus non-smokers was 4.5 [95% confidence interval (CI): 3.0-6.8] and 4.2 (95% CI: 2.4-7.2), for men and women, respectively. When divided by histologic type, relative risk for squamous cell carcinoma and small cell carcinoma was 12.7 (95% CI: 4.7-34.7) and 17.5 (95% CI: 4.9-62.1), while for adenocarcinoma it was 2.8 (95% CI: 1.6-4.9) and 2.0 (95% CI: 0.8-5.0) for men and women, respectively. We confirmed that the lung cancer risk in men rose with increasing cigarette smoking, especially the duration of smoking among current smokers and decreased after the cessation of smoking among former smokers. Unlike the US or European countries, the relative risk did not increase in this updated study, compared with previous studies in 1960s to 1990s in Japan either for all incident cases or for specific histologic types and the magnitude of relative risks was substantially lower than that observed in the US or European countries, especially for adenocarcinoma.     

Phase I-II study of biweekly paclitaxel administration with fixed-dose-rate cisplatin in advanced gastric cancer

Background Both paclitaxel (TXL) and cisplatin (CDDP) show efficacy against gastric cancer. The aim of this phase I-II study was to determine the maximum tolerated dose (MTD) and to evaluate the toxicity and efficacy of combination chemotherapy with these two agents. Methods Nineteen patients entered the phase I part of the study, and 21 patients entered the phase II part. TXL infusions were administered on days 1 and 15, with a fixed 3mg/m² dose of CDDP. Results In the phase I part of the study, we determined dose level 5, which represented a TXL dose of 18mg/m², with CDDP 3mg/m², to be the MTD. The recommended dose (RD) was level 4, with a TXL dose of 16mg/m² with CDDP, 3mg/m². In the phase II part of the study, the response rate was 25.0%; five patients had a partial response, seven had stable disease, 6 had progressive disease, and 2 were not evaluable. Grade 3 or 4 neutropenia was the most common adverse event and occurred in 65% of the patients. During treatment, 25% of the patients received granulocyte colony-stimulating factor, but febrile neutropenia was not shown in any of the patients. Major nonhematological toxicities were nausea/vomiting, anorexia, fatigue, alopecia, and sensory neuropathy. Adverse reactions of grade 3 or 4 were shown by two patients, one with anorexia (5%) and the other with sensory neuropathy (5%). Conclusion The RD was determined to be TXL 14mg/m², with CDDP 3mg/m².     

Smoking and risk of premature death among middle-aged Japanese: ten-year follow-up of the Japan Public Health Center-based prospective study on cancer and cardiovascular diseases (JPHC Study) cohort I.

To update the evidence on the association between smoking and mortality, we analyzed data from a population-based prospective study in Japan. In total, 19950 men and 21534 women aged 40 - 59 who reported their smoking history and had no serious disease at baseline survey were followed. During 1990 - 1999, 1014 men and 500 women died. Smokers were associated with an unhealthy lifestyle. Relative risks (RRs) for selected cause of death due to smoking were slightly attenuated by adjusting for possible confounding factors. Age- and area-adjusted RRs of male current smokers compared with never smokers were 1.66 (95% confidence intervals (CI): 1.40, 1.95) for all causes, 1.69 (1.31, 2.18) for all cancers, 1.67 (1.20, 2.34) for all circulatory system disease, and 1.63 (1.24, 2.15) for other causes, while those of females were 2.03 (1.52, 2.73), 2.06 (1.35, 3.15), 2.99 (1.75, 5.11), 1.31 (0.69, 2.51), respectively. After adjusting for multivariate variables, the corresponding RRs of male smokers were 1.55 (1.29, 1.86), 1.61 (1.20, 2.15), 1.41 (0.97, 2.03), and 1.61 (1.17, 2.19), against 1.89 (1.36, 2.62), 1.83 (1.14, 2.95), 2.72 (1.45, 5.07), and 1.39 (0.71, 2.73) for females. Twenty-two percent of death from all causes, 25% of all cancer, and 17% of all circulatory system disease deaths, could be attributed to cigarette smoking in males, and 5%, 4%, and 11% in females, respectively. Cumulative dose as indicated by pack-years was clearly associated with cancer death. These findings provided information as to the quantitative risk for premature death due to smoking among middle-aged Japanese men and women, and showed that the elevated risk was not explained by the unhealthy lifestyle of smokers.     

A Case-Control Study of the Effectiveness of Cervical Cancer Screening in Osaka, Japan

In the small town of Nose in Osaka, Japan, a population-based screening program for cervical cancer by Papanicolaou smear has been conducted since 1965. In order to evaluate the effectiveness of screening in terms of the reduction of the mortality and the incidence of invasive cervical cancer, two types of case-control studies were carried out. In the first study, the case series consisted of all women who died of cervical cancer under 80 years of age at the time of diagnosis in 1965-1987 (N = 15). For each case, 10 controls were chosen from living residents, matched by year of birth. It showed that the odds ratio (OR) of dying of cervical cancer for screened versus non-screened women was 0.22 (95%CI = 0.03-1.95). In the second study, the case series consisted of all women who were diagnosed as having invasive cancer under 80 years of age at the time of diagnosis in the same period (N = 28). For each case, 10 controls were chosen from living residents without invasive cancer, matched by year of birth and according to whether or not they were screened at the year of the diagnosis of the matched case. It showed that the OR of getting invasive cancer for screened versus non-screened women was 0,41 (95%CI = 0.13-1.29). From these results, it was estimated that 78% of cervical cancer mortality and 59% of invasive cervical cancer incidence among non-screened women could be prevented by cervical cancer screening.     

Impact of nuclear galectin-3 expression on histological differentiation and vascular invasion in patients with esophageal squamous cell carcinoma

Expression of galectin-3, a member of the beta-galactosidase binding lectin family, is reported to correlate with cell adhesion. The present immunohistochemical study was performed to clarify the impact of galectin-3 expression on patients with esophageal squamous cell carcinoma. Galectin-3 expression was examined immunohistochemically in 154 patients with esophageal squamous carcinoma, who had undergone surgery without preoperative supplemental therapy at the Department of Surgery II in the Hospital of the Faculty of Medicine, Oita University, between 1990 and 2000. The cases with > or =30% nuclear-stained cancer cells were considered high nuclear expression cases. In contrast, the cases with > or =45% cytoplasm-stained cancer cells were considered high cytoplasm expression cases. Twenty-three of 154 ESCC cases were regarded as high nuclear expression (14.9%) and 72 of 154 cases were regarded as high cytoplasm-expression (46.5%). High expression of galectin-3 in the nuclei inversely correlated with vascular invasion (p=0.030) and histological differentiation (p=0.0064). In contrast, cytoplasmic expression of galectin-3 revealed no significant impact on clinicopathological factors. Neither nuclear nor cytoplasmic expression of galectin-3 was a prognostic indicator in ESCC. Elevated expression of galectin-3 in the nuclei but not the cytoplasm may be an important biological parameter related to histological differentiation and vascular invasion in patients with ESCC.     

Role of the N-linked glycans of the prM and E envelope proteins in tick-borne encephalitis virus particle secretion

The tick-borne encephalitis (TBE) virus has two membrane glycoproteins (prM and E), which each has one N-linked glycan. Constructs that express prM and E proteins of TBE virus have been shown to produce virus-like particles (VLPs), which have surface properties that are similar to those of infectious viruses. To reveal the function of glycosylation of the TBE virus prM and E proteins in the secretion of VLPs, we expressed glycosylation-mutated prM and E proteins and compared the secretion levels and biological properties of the VLPs. In the prM protein glycosylation-deficient mutant, the level of secreted E protein was reduced to 60% of the wild-type level. On the other hand, in the E or prM-E protein glycosylation-deficient mutant, the level of secreted E protein was reduced to 10% of the wild-type level. Furthermore, the mutant which was glycosylated at positions 66 and 154 in protein E, the level of secreted E protein was four-fold higher than that of the wild-type. However, in the mutant which was glycosylated at position 66 only, E protein secretion was reduced to only 10% of the wild-type level. These data suggest that the glycan associated with the N-linked glycosylation site at position 154 in protein E plays an important role in VLP secretion.