The single nucleotide polymorphism upstream of insulin-induced gene 2 ( INSIG2) is associated with the prevalence of hypercholesterolaemia, but not with obesity, in Japanese American women

Insulin-induced gene 2 (insig-2) protein is known to play important roles in cholesterol and TAG metabolism both in vivo and in vitro. One particularly interesting single nucleotide polymorphism (SNP), rs7566605, located 10 kb upstream of INSIG2 was reported to have the strongest association with obesity among 86 604 SNP, while the relationship with dyslipidaemia is uncertain. Eight hundred and eighty-five Japanese Americans (347 men and 538 women) and 378 Japanese (182 men and 196 women) were enrolled, and the rs7566605 SNP, which is consistent with either G or C, was determined. We investigated the association between the rs7566605 SNP and the prevalence of hypercholesterolaemia or hypertriacylglycerolaemia, or obesity parameters, as assessed by BMI, waist girth and percentage body fat. There were no significant differences in BMI, waist girth and percentage body fat according to the genotype in each of the four groups, which was divided by population and sex. The prevalence of hypercholesterolaemia was significantly different between the genotypes in Japanese American female subjects (GG, 62.2 %; GC, 57.1 %; CC, 42.1 %; P = 0.021), but not in the other subjects. In Japanese American women, the subjects with the CC genotype had a 0.43-fold decreased risk (95 % CI 0.24, 0.80) for hypercholesterolaemia compared with the GG genotype after adjustment for age, percentage body fat, smoking status and hormone replacement therapy. The CC genotype of the rs7566605 SNP is suggested to be a protective genetic factor against the progression of hypercholesterolaemia on a high-fat diet, especially in Japanese female subjects.     

Analysis of 256 cases of basal cell carcinoma after either one-step or two-step surgery in a Japanese institution

Basal cell carcinoma (BCC) is a common skin cancer that arises from the cells of the basal layer of the epithelium or from the external root sheath of the hair follicle. In the present report, 256 cases treated surgically between 1999 and 2008 in our department were retrospectively analyzed. The most frequent BCC locations included the face (77.8%), especially the nose (26.9%) and eyelids (21.5%). Incomplete excisions occurred in 21 cases. Two patients experienced local recurrence; one of these patients exhibited a bone metastasis while the other had a metastasis of the parotid gland without the local recurrence. The rate of local BCC recurrence was 0.78%, which is lower than that described in previous reports. We categorized BCC into four histological types: superficial, solid, adenoid and infiltrative. The solid type was the most frequent histological type (62.1%). For preventive recurrence, we treated BCC patients with two-step surgery when the tumor was large or histologically invasive. At the first step, we excised the tumor with a sufficient safety margin, and at the second step, we performed reconstruction after the histological confirmation that no remnant malignant cells were in the tumor margins. In the present report, no local recurrence occurred in patients following the two-step surgery. Therefore, two-step surgery is recommended for tumors at locations and with histological types related to frequent recurrence.     

Cigarette smoking decreases dynamic inspiratory capacity during maximal exercise in patients with type 2 diabetes

To investigate the influence of cigarette smoking on exercise capacity, respiratory responses and dynamic changes in lung volume during exercise in patients with type 2 diabetes. Forty-one men with type, 2 diabetes without cardiopulmonary disease were recruited and divided into 28 non-current smokers and 13 current smokers. All subjects received lung function tests and cardiopulmonary exercise testing using tracings of the flow-volume loop. Exercise capacity was compared using the percentage of predicted oxygen uptake at maximal workload (%VO2max). Respiratory variables and inspiratory capacity (IC) were compared between the two groups at rest and at 20%, 40%, 60%, 80% and 100% of maximum workload. Although there was no significant difference in lung function tests between the two groups, venous carboxyhemoglobin (CO-Hb) levels were significantly higher in current smokers. %VO2max was inversely correlated with CO-Hb levels. Changing patterns in respiratory rate, respiratory equivalent and IC were significantly different between the two groups. Current smokers had rapid breathing, a greater respiratory equivalent and a limited increase in IC during exercise. Cigarette smoking diminishes the increase in dynamic IC in patients with type 2 diabetes. As this effect of smoking on dynamic changes in lung volume will exacerbate dynamic hyperinflation in cases complicated by chronic obstructive pulmonary disease, physicians should consider smoking habits and lung function when evaluating exercise capacity in patients with type 2 diabetes.     

Circulating visfatin level is correlated with inflammation, but not with insulin resistance

OBJECTIVE: Recent studies, both in vitro and in vivo, have indicated that visfatin is one of the inflammatory cytokines, although the relationship between visfatin and insulin resistance remains inconclusive. Accordingly, we assessed the association between visfatin concentrations in serum and those of interleukin-6 (IL-6) and C-reactive protein (CRP), known as markers of systemic inflammation, and also investigated the relationship between these serum concentrations and insulin resistance. DESIGN AND METHOD: A total of 295 Japanese Americans living in Hawaii (126 men and 169 women, mean age 68.7 +/- 14.9 years) were enrolled. The serum levels of visfatin, IL-6 and CRP levels were measured, and homeostasis model assessment for insulin resistance (HOMA-IR) was calculated as a marker of insulin resistance. RESULTS: Significant positive correlations were found between serum levels of visfatin and IL-6 or CRP (r = 0.271, P < 0.001; r = 0.118, P < 0.05, respectively). Multiple regression analysis revealed that correlations between serum levels of visfatin and IL-6 or CRP remained significant after adjustments for age, sex, body mass index, per cent body fat and waist girth. There was no significant trend of the HOMA-IR for the tertiles of serum concentrations of visfatin. On the other hand, a significant trend towards increase of HOMA-IR with increasing tertile of serum concentrations, from the lowest to the highest, was observed for both IL-6 and CRP. The HOMA-IR in subjects with serum concentration of IL-6 or CRP in the highest or intermediate tertiles of IL-6 or CRP were significantly higher than that in subjects in the lowest tertile, even after adjustment for age and sex (IL-6: P < 0.001 and P < 0.001, respectively; CRP: P < 0.001 and P < 0.01, respectively). CONCLUSION: Serum visfatin levels were positively correlated with the serum levels of IL-6 and slightly related with serum levels of CRP, but not with HOMA-IR, in Japanese Americans. Our results indicate that circulating visfatin may reflect inflammation status.     

Cancer-testis antigen lymphocyte antigen 6 complex locus K is a serologic biomarker and a therapeutic target for lung and esophageal carcinomas

Gene expression profile analyses of non-small cell lung carcinomas (NSCLC) and esophageal squamous cell carcinomas (ESCC) revealed that lymphocyte antigen 6 complex locus K (LY6K) was specifically expressed in testis and transactivated in a majority of NSCLCs and ESCCs. Immunohistochemical staining using 406 NSCLC and 265 ESCC specimens confirmed that LY6K overexpression was associated with poor prognosis for patients with NSCLC (P = 0.0003), as well as ESCC (P = 0.0278), and multivariate analysis confirmed its independent prognostic value for NSCLC (P = 0.0035). We established an ELISA to measure serum LY6K and found that the proportion of the serum LY6K-positive cases was 38 of 112 (33.9%) NSCLC and 26 of 81 (32.1%) ESCC, whereas only 3 of 74 (4.1%) healthy volunteers were falsely diagnosed. In most cases, there was no correlation between serum LY6K and conventional tumor markers of carcinoembryonic antigen (CEA) and cytokeratin 19-fragment (CYFRA 21-1) values. A combined ELISA for both LY6K and CEA classified 64.7% of lung adenocarcinoma patients as positive, and the use of both LY6K and CYFRA 21-1 increased sensitivity in the detection of lung squamous cell carcinomas and ESCCs up to 70.4% and 52.5%, respectively, whereas the false positive rate was 6.8% to 9.5%. In addition, knocked down of LY6K expression with small interfering RNAs resulted in growth suppression of the lung and esophageal cancer cells. Our data imply that a cancer-testis antigen, LY6K, should be useful as a new type of tumor biomarker and probably as a target for the development of new molecular therapies for cancer treatment.