HPV infection and immunochemical detection of cell-cycle markers in verrucous carcinoma of the penis

Penile verrucous carcinoma is a rare disease and little is known of its aetiology or pathogenesis. In this study we examined cell-cycle proteins expression and correlation with human papillomavirus infection in a series of 15 pure penile verrucous carcinomas from a single centre. Of 148 penile tumours, 15 (10%) were diagnosed as pure verrucous carcinomas. The expression of the cell-cycle-associated proteins p53, p21, RB, p16INK4A and Ki67 were examined by immunohistochemistry. Human papillomavirus infection was determined by polymerase chain reaction to identify a wide range of virus types. The expression of p16INK4A and Ki67 was significantly lower in verrucous carcinoma than in usual type squamous cell carcinoma, whereas the expression of p53, p21 and RB was not significantly different. p53 showed basal expression in contrast to usual type squamous cell carcinoma. Human papillomavirus infection was present in only 3 out of 13 verrucous carcinomas. Unique low-risk, high-risk and mixed viral infections were observed in each of the three cases. In conclusion, lower levels of p16INK4A and Ki67 expressions differentiate penile verrucous carcinoma from usual type squamous cell carcinoma. The low Ki67 index reflects the slow-growing nature of verrucous tumours. The low level of p16INK4A expression and human papillomavirus detection suggests that penile verrucous carcinoma pathogenesis is unrelated to human papillomavirus infection and the oncogenes and tumour suppressor genes classically altered by virus infection.Peer reviewedFinal Accepted Versio

Impact of single nucleotide polymorphism on short stature and reduced tongue pressure among community-dwelling elderly Japanese participants: a cross-sectional study

Background: Asian-specific single nucleotide polymorphism (SNPs) (rs3782886) is reported to be associated with myocardial infarction; sarcopenia is reported to be associated with coronary subclinical atherosclerosis. On the other hand, short stature has been revealed as an independent risk factor for cardiovascular disease. However, no studies have reported on the association between sarcopenia and short stature nor on the impact of rs3782886 on this association. Methods: Since reduced maximum voluntary tongue pressure against the palate (MTP) reflects one aspect of sarcopenia, we conducted a cross-sectional study of 537 community-dwelling elderly Japanese participants aged 60?89 years who had participated in a general health checkup in 2015. Short stature was defined as values at or under the 25th percentile, and reduced MTP was defined as the lowest tertile of the study population (<158.0 cm and <26.5 kPa for men, <145.0 cm and <24.1 kPa for women). Results: Independent of classical cardiovascular risk factors, short stature was revealed to be positively associated with reduced MTP. The adjusted-odds ratio (OR) and 95% confidence interval (CI) of reduced MTP for short stature was 1.87 (1.19, 2.94). We also found that independent of known cardiovascular risk factors, with the non-minor homo of rs3782886 taken as the reference group, the adjusted OR and 95% CI for short stature and reduced MTP of the minor homo allele were 3.06 (1.23, 7.63) and 3.26 (1.33, 8.03), respectively. Conclusion: Short stature is independently associated with reduced MTP, with Asian-specific SNPs possibly playing an important role in this association

Triglycerides and blood pressure in relation to circulating CD34-positive cell levels among community-dwelling elderly Japanese men: a cross-sectional study

Background: Triglycerides are reported to be positively associated with blood pressure (both systolic and diastolic). However, in a previous study, we reported a significant positive association between triglycerides and circulating CD34-positive cells (endothelial repair) among non-hypertensive, but not hypertensive, participants. Since hypertension and endothelial dysfunction have a bi-directional association (vicious cycle), the status of circulating CD34-positive cells may influence the association between triglycerides and hypertension. Methods: Since antihypertensive medication use may influence results of the present study, we conducted a cross-sectional study of 327 community dwelling elderly (aged 60-69 years) Japanese participants who were not taking anti-hypertensive medication and who had participated in a general health check-up in 2013-2015. Results: Participants were classified into two groups based on median values of circulating CD34-positive cells (0.93 cells/μL). For participants with lower circulating CD34-positive cells (n = 165), a significant positive association was seen between triglycerides and blood pressure, but not for participants with higher circulating CD34-positive cells (n = 162). The multivariable standardized parameter estimates (β) and p values of systolic blood pressure and diastolic blood pressure were 0.23 (p = 0.007) and 0.18 (p = 0.036) for participants with lower circulating CD34-positive cells and 0.08 (p = 0.409) and 0.03 (p = 0.786) for those with higher circulating CD34-positive cells. Conclusion: A significant positive association between triglycerides and blood pressure exists among those with lower, but not higher, circulating CD34-positive cells. The level of circulating CD34-positive cells acts as a determinant factor for the association between triglycerides and blood pressure

Association between high-density lipoprotein-cholesterol and hypertension in relation to circulating CD34-positive cell levels

Background: Although high-density lipoprotein-cholesterol (HDL) level is inversely correlated with cardiovascular events, HDL is also reported to be positively associated with hypertension, which is a known endothelial impairment factor. Since HDL mediates important protective actions on the vascular endothelium by increasing the number of circulating endothelial progenitor cells (CD34-positive cells), the level of circulating CD34-positive cells should influence the association between HDL and hypertension. Methods: To investigate the association between HDL and hypertension in relation to the level of circulating CD34-positive cells, we conducted a cross-sectional study of 477 elderly men aged 60?69 years who participated in general health checkup. Results: HDL was found to be significantly positively associated with hypertension in subjects with a high level of circulating CD34-positive cells, while no significant association was observed for subjects with low circulating CD34-positive cells. Known cardiovascular risk factors adjusted odds (ORs) and 95% confidence intervals (CIs) of hypertension for increments of one standard deviation (SD) in HDL (13.8 mg/dL) were 1.44 (1.06, 1.96) for subjects with a high level of circulating CD34-positive cells and 0.87 (0.63, 1.19) for subjects with low circulating CD34-positive cells. We also revealed a significant association between HDL level and CD34-positive cell level on hypertension, with fully adjusted p values for the effect of this interaction on hypertension at 0.022. Conclusions: Independent of known cardiovascular risk factors, HDL was found to be positively associated with hypertension in subjects with a high level of circulating CD34-positive cells but not for subjects with low circulating CD34-positive cells

Reticulocyte levels have an ambivalent association with hypertension and atherosclerosis in the elderly: a cross-sectional study

Yuji Shimizu,1,2 Shin-Ya Kawashiri,1 Hirotomo Yamanashi,3,4 Jun Koyamatsu,3 Shoichi Fukui,1 Hideaki Kondo,1,4 Mami Tamai,1 Seiko Nakamichi,4 Takahiro Maeda1,3&ndash;41Department of Community Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan; 2Department of Cardiovascular Disease Prevention, Osaka Center for Cancer and Cardiovascular Disease Prevention, Osaka, Japan; 3Department of Island and Community Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan; 4Department of General Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, JapanPurpose: Age-related reduction in bone marrow activity has been shown to cause anemia, and hypertension and endothelial dysfunction (atherosclerosis) are age-related diseases. However, recent studies have revealed a close association between bone marrow activity and endothelial maintenance. This study aimed to determine the association between elevated reticulocyte levels in conjunction with vigorous bone marrow activity and hypertension and atherosclerosis among the elderly.Study population and Methods: To determine the associations between reticulocyte levels and hypertension and atherosclerosis, we conducted a cross-sectional study of 2,098 elderly Japanese individuals, aged between 60 and 89&nbsp;years, who had participated in an annual health check-up in 2014.Results: Of the total study population, 1,348 individuals were diagnosed with hypertension (systolic blood pressure &ge;140&nbsp;mmHg and/or diastolic blood pressure &ge;90&nbsp;mmHg and/or having used antihypertensive medication), and 393 were diagnosed with atherosclerosis (carotid intima-media thickness &ge;1.1 mm). Reticulocyte levels were found to be significantly positively associated with hypertension and inversely associated with atherosclerosis. Cardiovascular risk factor-adjusted odds ratios and 95% confidence intervals for hypertension and atherosclerosis, when raised incrementally by 1 standard deviation to determine reticulocyte levels (5.5&times;104&nbsp;cells/&mu;L for men and 5.0&times;104&nbsp;cells/&mu;L for women), were 1.12 (1.01, 1.25) and 0.83 (0.72, 0.94), respectively.Conclusion: Along with established cardiovascular risk factors, reticulocyte levels in elderly Japanese individuals were found to be positively associated with hypertension and inversely associated with atherosclerosis. This finding may help clarify the background mechanisms concerning the association between bone marrow activity and vascular remodeling.Keywords: atherosclerosis, hypertension, reticulocyt

Hepatocyte growth factor and carotid intima-media thickness in relation to circulating CD34-positive cell levels

Hepatocyte growth factor (HGF) may act as a possible biochemical index for vascular damage, although evidence for the association between HGF and carotid intima-media thickness (CIMT) is limited. Since both HGF and circulating CD34-positive cells play an important role in endothelial repair, circulating CD34-positive cell levels may influence the association between HGF and CIMT. Methods: We conducted a cross-sectional study of 269 elderly Japanese men aged 60-69 years who had undertaken an annual medical checkup from 2014 to 2015. Results: The median value for circulating CD34-positive cells was 0.93 cells/μL. Among the study population, 135 men showed low circulating CD34-positive cell levels (? 0.93 cells/μL). By multivariable linear regression analysis, HGF was found to be significantly positively associated with CIMT only to participants with low circulating CD34-positive cell levels, with a multi-adjusted β of 0.26 (p = 0.005) and 0.002 (0.986) for low and high circulating CD34-positive cell levels, respectively. In addition, a significant interaction was observed between HGF and circulating CD34-positive cell levels (low and high) on CIMT (multivariable p value of 0.049). A positive association exists between HGF and CIMT in elderly Japanese men, limited to participants with low circulating CD34-positive cell levels. Conclusion: A positive association exists between HGF and CIMT in community-dwelling elderly Japanese men, which is limited to participants with low numbers of circulating CD34-positive cells. Our findings indicate that circulating CD34-positive cell levels could determine the influence of HGF on CIMT in elderly Japanese men

Association between tongue pressure and subclinical carotid atherosclerosis in relation to platelet levels in hypertensive elderly men: a cross-sectional study

Background: Age-related low-grade inflammation causing endothelial disruption influences sarcopenia, hypertension, and atherosclerosis. We reported previously that maintenance of muscle strength in elderly hypertensive men with high platelet levels is positively associated with subclinical atherosclerosis but not in those with low platelet levels. Since reduced tongue pressure is related to sarcopenia, tongue pressure may be associated with subclinical carotid atherosclerosis in hypertensive elderly subjects, and platelet levels may function as an indicator of the association between tongue pressure and subclinical carotid atherosclerosis. Methods: We conducted a cross-sectional study of 342 hypertensive elderly Japanese men aged 60-89 who participated in an annual health check-up in 2015 and 2016. Subclinical carotid atherosclerosis was defined as a common carotid intima-media thickness (CIMT) of 1.1mm or more. Results: In the overall study population, 171 subjects demonstrated low platelets (<21.4×104/μL). Tongue pressure was significantly inversely associated with subclinical carotid atherosclerosis in these subjects, but not in subjects with high platelets. The known cardiovascular risk factor adjusted odds ratios (ORs) and 95% confidence intervals (CIs) of subclinical carotid atherosclerosis for a 1 standard deviation (SD) increment in tongue pressure (10.4kPa) were 0.54 (0.35, 0.85) and 1.31 (0.87, 1.96), respectively. Conclusion: Tongue pressure is inversely associated with subclinical carotid atherosclerosis in hypertensive elderly men with low platelet levels, but not in those with high levels. This finding may thus constitute an efficient tool for clarifying the background mechanism of age-related diseases such as sarcopenia, hypertension, and atherosclerosis