Risk of Lymph Node Metastasis in Patients with the Superficial Spreading Type of Esophageal Squamous Cell Carcinoma.

BACKGROUND: Little is known about the clinicopathological characteristics of superficial spreading-type esophageal carcinoma extending ≥5 cm along the long axis of the esophagus. This study was aimed at investigating the frequency of lymph node metastasis (LNM) in patients with superficial spreading-type esophageal carcinoma. METHODS: We reviewed the data of 320 patients with superficial esophageal squamous cell carcinoma who had undergone esophagectomy with lymph node dissection at our hospital between 1986 and 2010. The incidence of LNM was compared between the spreading (≥5 cm) and nonspreading (< 5 cm) types. RESULTS: The multivariate analysis revealed significant differences in the likelihood of LNM depending on the lymphovascular invasion, the infiltrative growth pattern (INF)-c, and the depth. There was no difference in the LNM frequency between nonspreading and spreading type in the patients with epithelium (EP)-lamina propria, muscularis mucosa (MM)-submucosa (SM)1 and SM2/3 lesions. The frequencies of LNMs (nonspreading-type vs. spreading-type tumors) in the patients with MM-SM1 lesions were 7/47 (14.9%) versus 4/25 (16%) and those in the patients with SM2/3 lesions were 22/58 (37.9%) versus 4/14 (28.9%), when the lesions did not have lymphovascular invasion and INF-c. CONCLUSIONS: Endoscopic resection can be selected for -EP-SM1 lesions, regardless of whether the lesions are of the spreading type or nonspreading type.

Severe rhabdomyolysis associated with severe fever with thrombocytopenia syndrome in a married couple: a case report.

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne infection that has recently emerged. This infectious disease is due to the transfer of SFTS virus (SFTSV) from the infected blood of animals to humans. Approximately 30% of patients who are infected with SFTS die from multiorgan failure associated with severe infection, systemic inflammatory response syndrome, or disseminated intravascular coagulation. We treated an elderly Japanese couple (husband and wife) who had genetically identical SFTSV infections and who both developed severe rhabdomyolysis. CASE PRESENTATION: An 80-year-old man presented to the clinic with a fever; his 74-year-old wife presented with a fever 9 days later. Their laboratory results at diagnosis showed severe rhabdomyolysis with significantly elevated creatinine kinase (detected levels: husband, 9546 U/L; wife, 15,933 U/L). The creatinine kinase isozyme was 100% MM type in both patients. In both the husband and wife, SFTSV was identified with real-time polymerase chain reaction analysis. The detected SFTSVs in both the husband and wife were identical according to the genome sequence analysis. The husband's bone marrow indicated macrophage activation syndrome, but he responded to supportive therapy. He was discharged after being hospitalized for 32 days. The wife was admitted to our hospital in critical condition 2 days after SFTS symptom onset. She died of multiorgan failure 8 days after onset, despite being cared for in an intensive care unit. Both of the patients presented with rhabdomyolysis following SFTS symptom onset. The patients' clinical outcomes were different from each other; i.e., the husband survived, and the wife died. CONCLUSIONS: SFTSV infection-associated rhabdomyolysis has been reported in one patient, and simultaneous onset in two related patients has not been described previously. Our findings suggest that similar biological responses occurred, but they resulted in different clinical outcomes in the patients infected by the identical SFTSV isolates. Notably, a patient's clinical outcome depends on their own immune response. We suggest that one component of viral rhabdomyolysis involves immune-mediated responses. Severe immunological responses may adversely affect the treatment outcome, as demonstrated by the wife's clinical course. Our findings demonstrate that a patient's immune response contributes to their prognosis following SFTSV infection.

Association between left ventricular hypertrophy and changes in arterial stiffness during hypertensive treatment.

Cardio-ankle vascular index (CAVI) has been demonstrated as a parameter of arterial stiffness, which antihypertensive therapy may improve. However, little information is available about the factors affecting changes in arterial stiffness assessed by CAVI during antihypertensive therapy. We performed a study to examine the factors affecting changes in arterial stiffness assessed by CAVI during antihypertensive therapy. Eighty treated hypertensive patients (71 ± 10 years) were divided into two groups: 50 patients showing a decrease in CAVI (Group 1) and 30 patients showing an increase (Group 2) during observation (24 ± 11 months) of antihypertensive therapy. The groups did not differ in the rates of use of angiotensin II receptor blockers or calcium channel blockers. Age (Group 1: 67 ± 11 versus Group 2: 74 ± 8 years), left ventricular mass index (LVMI) (Group 1: 103 ± 19 versus Group 2: 120 ± 24 g/m(2)) and systolic blood pressure (Group 1: 133 ± 17 versus Group 2: 144 ± 23 mm Hg) at the start of observation were significantly higher in Group 2 than in Group 1 (p = 0.003, p = 0.001 and p = 0.027, respectively). The changes in CAVI during observation were correlated only with LVMI (r = 0.289, p = 0.009) at the start of observation for all 80 patients. It may be difficult to improve arterial stiffness assessed by CAVI during antihypertensive therapy in hypertensive patients with left ventricular hypertrophy.

Association between oxidative stress assessed by urinary 8-hydroxydeoxyguanosine and the cardiac function in hypertensive patients without overt heart disease.

Although increased oxidative stress is known to be associated with worsened cardiac function in chronic heart failure, consensus is still lacking regarding the association between oxidative stress and cardiac function in hypertensive patients without overt heart disease. This study aimed to evaluate the association between oxidative stress assessed by urinary 8-hydroxydeoxyguanosine (8-OHdG) and cardiac function in hypertensive patients without overt heart disease. We enrolled a total of 80 hypertensive patients (70 ± 11 y) who had been taking antihypertensive medications for at least 1 year. Urinary 8-OHdG levels were measured by an immunochromatographic assay (ICR-001, Selista Inc., Tokyo, Japan). Echocardiography was performed to assess the left ventricular (LV) diastolic function by measuring early diastolic mitral annular velocity (e') and the ratio of early transmitral flow velocity (E) to e' (E/e'). Urinary 8-OHdG was correlated with E/e' (r = 0.346, P = .002), e' (r = -0.310, P = .005), and HbA1c (r = 0.276, P = .013). Multiple linear regression analysis revealed that only e' (ß = -0.343, P = .004) was an independent determinant of urinary 8-OHdG. In conclusion, decreased e' is independently associated with elevated urinary 8-OHdG, a marker of oxidative stress, in hypertensive patients. Therefore, an elevated urinary 8-OHdG level may be useful in detecting subclinical LV diastolic dysfunction in hypertensive patients without overt heart disease.

Comparison of Needle Knife versus Scissors Forceps for Colorectal Endoscopic Submucosal Dissection: A Prospective Randomized Study.

BACKGROUND AND AIM: To evaluate the efficacy and safety of a grasping-type knife, called Clutch Cutter (CC), for colorectal endoscopic submucosal dissection (C-ESD). METHODS: This was a randomized prospective study. Patients who underwent C-ESD for colorectal neoplasms >20 mm and <50 mm in size were enrolled, dividing into two groups: ESD using needle type of dual knife alone (D-group) and circumferential incision using dual knife followed by submucosal dissection using CC (CC-group). The primary outcome was the self-completion rate. The secondary outcomes were intraoperative complication rate, procedure time, and en bloc resection rate. RESULTS: A total of 45 patients were allocated to the D-group and 43 to the CC-group were allocated. The self-completion rate was higher in the CC-group (87% [39/45] vs. 98% [42/43]). All of the six patients with an incomplete procedure in the D-group were completely resected with CC use. The intraoperative complication rate was not significant in either group (D vs. CC: 2% vs. 0%). The mean procedure time was significantly shorter in the D-group than that in the CC-group (62.0 vs. 81.1 min; p = 0.0036). The en bloc resection rate was 100% in the D-group and 98% in the CC-group. CONCLUSIONS: While dual knife use is superior to CC in terms of time efficiency, the use of CC may be a safe and efficacious option for achieving complete C-ESD.

Association of serum anti-periodontal pathogen antibody with ischemic stroke.

BACKGROUND: Periodontitis increases the risk of atherosclerotic cardiovascular disease and ischemic stroke. In this study, we evaluated whether serum antibody levels against individual periodontal pathogens are significantly associated with ischemic stroke subtypes and their risk factors. METHODS: Patients with acute ischemic stroke (n = 132; 74 male and 58 female, 71.3 ± 10.7 years) and patients with no previous stroke (n = 77; 38 male and 39 female, 70.7 ± 9.5 years) were consecutively enrolled in this study. Stroke subtype was evaluated based on the Trial of Org 10172 in Acute Stroke Treatment classification. Serum was obtained from each patient after obtaining their consent to participate in the study. The levels of serum antibodies against Aggregatibacter actinomycetemcomitans (Aa), Porphyromonas gingivalis (Pg) and Prevotella intermedia (Pi) were evaluated by ELISA. Serum high-sensitivity C-reactive protein (hs-CRP) levels were measured by nephelometry. RESULTS: Serum hs-CRP levels were significantly associated with acute ischemic stroke even after controlling for acute ischemic stroke, hypertension, diabetes mellitus and bulb/ internal carotid artery (ICA) atherosclerosis which were statistically selected (coefficient 0.245, 95% CI 0.142-0.347, p < 0.0001). The serum-antibody level of Pi was significantly higher in atherothrombotic-stroke patients than in patients with no previous stroke (p = 0.0035). Detectable serum anti-Pg antibody was significantly associated with atrial fibrillation (overall χ(2) = 35.5, R(2) = 0.18, n = 209, p < 0.0001; anti-Pg antibody: OR 4.36, 95% CI 1.71-12.10, p = 0.0017), and detectable serum anti-Pi antibody was significantly associated with bulb/ICA atherosclerosis after controlling for the statistically selected associated factors (overall χ(2) = 46.1, R(2) = 0.18, n = 209, p < 0.0001; anti-Pg antibody: OR 16.58, 95% CI 3.96-78.93, p < 0.0001). The levels of serum anti-Pi antibody were significantly associated with atherothrombotic stroke with the statistically selected associated factors excluding bulb/ICA atherosclerosis (overall χ(2) = 77.0, R(2) = 0.44, n = 129, p < 0.0001; anti-Pi antibody: OR 23.6, 95% CI 2.65-298.2, p = 0.008). However, when we included bulb/ICA atherosclerosis in this model, the levels of serum anti-Pi antibody were no longer significantly associated with atherothrombotic stroke (overall χ(2) = 98.0, R(2) = 0.56, n = 129, p < 0.0001; anti-Pi antibody: p = 0.107). CONCLUSIONS: Our results suggest that anti-Pg antibody is associated with atrial fibrillation and that anti-Pi antibody is associated with carotid artery atherosclerosis. In addition, anti-Pi antibody may be associated with atherothrombotic stroke through its association with carotid artery atherosclerosis. Thus, periodontitis may lead to serious systemic diseases.

Clinical significance of autoantibodies to p53 protein in patients with autoimmune liver diseases.

BACKGROUND: Autoantibodies to p53 (anti-p53) are rarely present in the sera of patients with autoimmune diseases or the sera of patients with malignancies. OBJECTIVE: To examine the prevalence of anti-p53 in patients with autoimmune liver disease including autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), AIH/PBC overlap syndrome (AIH/PBC OS) and primary sclerosing cholangitis (PSC), and to determine the clinical significance of anti-p53 in autoimmune liver diseases. METHODS: Forty patients with AIH, 41 patients with PBC, eight patients with AIH/PBC OS and five patients with PSC were enrolled. Anti-p53 and antibodies to double-stranded DNA (anti-ds-DNA) were analyzed using commercially available ELISA kits. Demographic, laboratory and histological data were compared between the AIH groups seropositive and seronegative for anti-p53. RESULTS: Six of 40 (15.0%) patients with AIH and four of eight (50.0%) patients with AIH/PBC OS were positive for anti-p53. One of 41 (2.4%) patients with PBC was also positive for anti-p53, but all five patients with PSC were negative, indicating a significantly higher prevalence of anti-p53 in patients with AIH or AIH/PBC OS compared with patients with PBC. None of the AIH patients positive for anti-p53 progressed to hepatic failure or relapsed after immunosuppressive treatment. Titres of anti-ds-DNA in patients with AIH and AIH/PBC OS significantly correlated with titres of anti-p53 (r=0.511; P=0.0213). CONCLUSION: The emergence of anti-p53 is likely to be useful for discriminating AIH or AIH/PBC OS from PBC and helpful for predicting favourable prognoses in patients with AIH. DNA damage may trigger the production of anti-p53 in patients with AIH or AIH/PBC OS.

Clinical relevance of antibodies to cardiolipin in patients with chronic hepatitis C.

The significance of antibodies to cardiolipin (anti-CL) remains uncertain in patients with chronic hepatitis C (CH-C). The main purpose of this study was to elucidate the clinical characteristics of patients with CH-C seropositive for anti-CL. The prevalence of anti-CL and clinical parameters associated with anti-CL in those patients were examined. Six of the 45 (13%) patients with CH-C had anti-CL. However, none of these six CH-C patients fulfilled the criteria for antiphospholipid syndrome. Serum triglyceride and apolipoprotein B (ApoB) levels in CH-C patients with anti-CL were significantly higher than those in CH-C patients without anti-CL. Serum triglyceride levels positively correlated with serum ApoB levels. CH-C patients with anti-CL had significantly more progressive hepatic fibrosis than those without anti-CL. The degree of 8-hydroxy 2'-deoxyguanosine (8-OHdG) expression in the liver tissue was more severe in CH-C patients with anti-CL than in those without it. However, the emergence of anti-CL in CH-C patients was independent of insulin resistance, hepatic steatosis, and iron overload. These findings suggest that the emergence of anti-CL is associated with oxidative stress and that CH-C patients seropositive for anti-CL have clinical characteristics of hypertriglyceridemia, which derives from the facilitation of ApoB synthesis, and progressive hepatic fibrosis.

Reduced bone mineral density in hypertensive patients is associated with left ventricular diastolic dysfunction, not left ventricular hypertrophy.

Left ventricular (LV) hypertrophy and diastolic dysfunction are commonly observed in hypertensive patients, and have been demonstrated to be risk factors of chronic heart failure due to LV diastolic dysfunction. Recently, reduced bone mineral density has been found in hypertensive patients compared with healthy controls. However, relationships between bone mineral density and LV hypertrophy and diastolic dysfunction have not been fully assessed. We examined relationships between bone mineral density and both LV hypertrophy and diastolic dysfunction in 38 hypertensive patients (23 males, 15 females; mean age 71 ± 8 y) who had been treated with antihypertensive drugs for at least 1 year. The bone mineral density of the calcaneus was measured with a quantitative ultrasound measurement device (A-1000 EXPRESS/InSight, GE Healthcare, Horten, Norway), and the stiffness index was determined as a parameter of bone mineral density. Echocardiography was performed to measure the left ventricular mass index as a parameter of LV hypertrophy. Left ventricular diastolic dysfunction was also assessed by early diastolic mitral annular velocity (e'), and the ratio of early transmitral flow velocity (E) to e' (E/e'). The bone mineral density did not correlate with left ventricular mass index, but did correlate with e' (r = 0.453, P < .01) and E/e' (r = -0.359, P < .05). Thus, reduced bone mineral density in hypertensive patients is not associated with LV hypertrophy but with LV diastolic dysfunction. Hypertensive patients with reduced bone mineral density may have a high risk of chronic heart failure due to LV diastolic dysfunction as well as bone fractures due to osteoporosis.

Endoscopic features of colorectal lymphoma according to histological type.

Background and Aim: This study aimed to investigate the relationship between the histological type of colorectal lymphoma and its endoscopic features. Methods: We retrospectively analyzed patients with primary colorectal lymphoma who were diagnosed using colonoscopy and biopsy specimens at the National Cancer Center Hospital, Tokyo, Japan. The lesions were macroscopically classified into the following types via colonoscopy: polypoid, ulcerative, multiple lymphomatous polyposis, diffuse, and mixed. Results: A total of 117 lesions were identified in 90 patients enrolled in this study. Of these, 59 (50%) were located in the ileocecal region, 23 (20%) in the rectum, 9 (8%) in the transverse colon, 8 (7%) in the sigmoid colon, 7 (6%) in the descending colon, and 4 (3%) in the ascending colon. Moreover, the most common histological subtypes were diffuse large B-cell lymphoma (DLBCL) in 39 patients (43%) and mantle cell lymphoma (MCL) in 23 patients (26%), followed by follicular lymphoma (FL; 17%), mucosa-associated lymphoid tissue (MALT) lymphoma (9%), peripheral T-cell lymphoma-NOS (2%), monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL; 2%), and Burkitt lymphoma (1%). More than half of the DLBCL (52%), MCL (52%), and MALT (56%) lymphomas were macroscopically classified as polypoid types. In contrast, FL lesions showed various macroscopic types. The majority of DLBCL (62%) and FL (78%) lesions were distributed in the ileocecal region. MCL lesions tended to be widely spread in various sites of the large intestine. Conclusions: Colorectal lymphomas showed macroscopically distinctive features depending on the histological type. Understanding the macroscopic classification of the lesions by colonoscopy and its distribution may be helpful in diagnosing the type of lymphoma and determining the malignant grade based on the histological types.

Association between echocardiographic parameters and brain natriuretic peptide levels in treated hypertensive patients.

We examined which echocardiographic parameter correlated best with plasma brain natriuteric peptide (BNP) levels in treated hypertensive patients. Enrolled in the study were 122 treated hypertensive patients (70 ± 9 y). The left ventricular mass index and left atrial dimension (LAD) were measured using echocardiography as indexes of left ventricular hypertrophy and left atrial enlargement, respectively. Among all the echocardiographic parameters, LAD correlated best with BNP (r = 0.343, p < 0.001). Stepwise regression analysis showed that LAD (ß coefficient = 0.513, p < 0.001) was independently associated with BNP. Left atrial enlargement, rather than left ventricular hypertrophy, may be clinically useful for predicting elevated BNP levels in treated hypertensive patients.

Seasonal variation in estimated glomerular filtration rate based on serum creatinine levels in hypertensive patients.

Seasonal variations in blood pressures should be kept in mind when controlling blood pressure in hypertensive patients. Seasonal variations in glomerular filtration rate (GFR) also may have a clinical significance. However, it is time-consuming to measure GFR directly. We therefore examined the seasonal variation in estimated glomerular filtration rate (eGFR) based on serum creatinine levels in hypertensive patients without CKD (eGFR ≥ 60 mL/min/1.73 m(2)) and those with chronic kidney disease (CKD) (eGFR < 60 mL/min/1.73 m(2)). This study included 47 hypertensive patients without CKD (69 ± 11 yrs) and 55 hypertensive patients with CKD (76 ± 8 yrs). The eGFR was determined from the equation: eGFR = 194 × age(-0.287) × (serum creatinine)(-1.094) (× 0.739 if female). Overall, both groups of hypertensive patients demonstrated similar seasonal variations in eGFR. Importantly, hypertensive patients without CKD and those with CKD showed the lower eGFR in summer (June-August) (71.8 ± 13.2 and 37.2 ± 13.0 mL/min/1.73 m(2), respectively) compared with the eGFR in spring (March-May) (77.9 ± 13.0 and 43.0 ± 14.0 mL/min/1.73 m(2), respectively) (p < 0.05). The decrease in eGFR from spring to summer was similar for both types of hypertensive patients (without CKD, -6.1 ± 7.0; with CKD, -5.8 ± 5.2 mL/min/1.73 m(2)). However, the percent change in eGFR from spring to summer was greater in hypertensive patients with CKD (-13.8 ± 9.4 %) than in those without CKD (-7.7 ± 8.3 %) (p = 0.001). In conclusion, careful observation regarding renal function is needed for hypertensive patients with CKD during summer.

Association between bone mineral density and arterial stiffness in hypertensive patients.

Hypertension and osteoporosis are two common diseases in the elderly population. Recently, reduced bone mineral density has been found in hypertensive patients compared with healthy controls. Reduced bone mineral density is associated with increased arterial stiffness in chronic dialysis patients and healthy postmenopausal women. However, relationships between bone mineral density and arterial stiffness in hypertensive patients have not been fully assessed. We examined the relationships between bone mineral density and both arterial stiffness and nutritional status in 52 hypertensive patients (27 male and 25 female subjects; mean age 71±8 years) who had been treated with antihypertensive drugs for at least one year. The bone mineral density of the calcaneus was measured with a quantitative ultrasound measurement device, and the stiffness index was determined as a parameter of the bone mineral density. We measured the cardio-ankle vascular index (CAVI) to assess arterial stiffness and used the serum albumin to assess nutritional status. Increased arterial stiffness as assessed with CAVI is associated with reduced bone mineral density (r=-0.289, p=0.038). However, the correlation between CAVI and bone mineral density is not as strong as the correlation between serum albumin and bone mineral density (r=0.501, p<0.001). In conclusion, nutritional status is an important indicator of bone mineral density in hypertensive patients. Moreover, increased arterial stiffness is associated with reduced bone mineral density in hypertensive patients. Therefore, hypertensive patients with increased arterial stiffness may have a high risk of bone fracture due to osteoporosis.

Association between high-sensitivity C-reactive protein and left ventricular diastolic function assessed by echocardiography in patients with cardiovascular risk factors.

High-sensitivity C-reactive protein (hsCRP) has been demonstrated to play a causal role in atherosclerosis and to predict cardiovascular events in the general population. On the other hand, left ventricular (LV) hypertrophy and diastolic dysfunction assessed by echocardiography can also predict cardiovascular events in patients with cardiovascular risk factors. However, there are few data regarding the relationships among hsCRP, LV hypertrophy, and diastolic function. We examined the relationships among hsCRP, LV hypertrophy, and diastolic function in 185 patients (65±11 years), who had no overt heart disease, but had cardiovascular risk factors, including hypertension, diabetes, and dyslipidemia. Echocardiography was performed to measure the left ventricular mass index (LVMI) as a parameter of LV hypertrophy. LV diastolic function was assessed by the ratio (E/A) of early (E) and late (A) diastolic transmitral flows, early diastolic mitral annular velocity (E'), and the ratio (E/E') of E to E' using Doppler echocardiography. The hsCRP was correlated with LVMI (r=0.228, p=0.002), E' (r=-0.276, p<0.001), and E/E' (r=0.419, p<0.001). The E/E' as a parameter of LV diastolic function showed the closest correlation to hsCRP. These results indicate that elevated hsCRP reflects LV diastolic dysfunction rather than LV hypertrophy. We therefore suggest that hsCRP may be a marker of subclinical LV diastolic dysfunction in patients with cardiovascular risk factors.

Correlation of arterial stiffness to left ventricular function in patients with reduced ejection fraction.

Heart failure has been divided into heart failure with preserved left ventricular (LV) ejection fraction (EF) and heart failure with reduced EF, because the pathophysiologies of the two conditions are different. Cardio-ankle vascular index (CAVI) is a new indicator of arterial stiffness, and the most conspicuous feature of CAVI is its independence of blood pressure at the time of measurement. Arterial stiffness has been considered to increase LV afterload, which requires special care to avoid the onset of heart failure. We compared the correlation of arterial stiffness as assessed by CAVI to LV function in 44 hypertensive patients with preserved EF (EF: 71 ± 7%) and 31 patients with reduced EF (48 ± 8%). All of patients with reduced EF had history of both hypertension and myocardial infarction. Using Doppler echocardiography, LV diastolic and systolic function was evaluated by measuring peak early diastolic mitral annular velocity (e') and global LV peak systolic longitudinal strain (GPSLS), respectively. In patients with preserved EF, CAVI was correlated with e' (r = -0.313, p = 0.038), but not with GPSLS (r = 0.207). By contrast, CAVI was correlated with GPSLS (r = 0.604, p < 0.001) as well as e' (r = -0.393, p = 0.029) in patients with reduced EF. Thus, patients with reduced EF showed a closer correlation of arterial stiffness to LV function compared with patients with preserved EF. Therefore, hypertensive patients with reduced EF require a stricter regimen for treating arterial stiffness than their counterparts with preserved EF.

Premedication of hemin for eradication therapy of Helicobacter pylori in patients with porphyria.

Eradication therapy of Helicobacter pylori may be safe if hemin has been intravenously administered in advance, even in patients with a history of recurrent acute porphyria attack.

Exendin-4 regulates pancreatic ABCA1 transcription via CaMKK/CaMKIV pathway.

ATP-binding cassette transporter A1 (ABCA1) in pancreatic beta cells influences insulin secretion and glucose homeostasis. This study investigates whether the long-acting agonist of the glucagon-like peptide 1, namely exendin-4, which mediates stimulatory effects on ABCA1 gene expression, could interfere with the Ca(2+)/calmodulin (CaM)-dependent protein kinase (CaMK) cascade. ABCA1 promoter activity was examined by reporter gene assay in rat insulin-secreting INS-1 cells incubated with exendin-4. CaMKIV activity was assessed by detection of activation-loop phosphorylation (Thr(196)) of CaMKIV. We investigated the influence of the constitutively active form (CaMKIVc) or CaMKIV knockdown on ABCA1 expression. Increased abundance of ABCA1 protein was noted in response to rising concentrations of exendin-4 with maximum induction at 10 nM. Exendin-4 also stimulated ABCA1 promoter activity, but failed to do so in the presence of STO-609, a CaMKK inhibitor. Up-regulation of CaMKIV phosphorylation (at Thr(196)) peaked after 10 min. of exposure to exendin-4. CaMKIVc enhanced or up-regulated ABCA1 promoter activity in INS-1 cells. Furthermore, exendin-4 induction of ABCA1 protein expression was significantly suppressed in cells treated with CaMKIV-siRNA. Activation of the CaMKK/CaMKIV cascade by exendin-4 stimulated ABCA1 gene transcription, indicating that exendin-4 plays an important role in insulin secretion and cholesterol ester content in pancreatic beta cells.

Differences between hypertensive and atherosclerotic lesions in retinal arteries assessed by Scheie's classification in hypertensive patients following stroke.

Scheie's classification regarding hypertensive and atherosclerotic lesions in retinal arteries is generally used to assess the severity of hypertensive retinopathy and the risks of cardiovascular events in hypertensive patients. However, the differences between these two types of retinal artery lesions have not been fully examined. Both arterial stiffness and aortic root diameter are increased in hypertensive patients. The aim of this study was to elucidate differences in the two types of lesions by comparing their relationships to arterial stiffness and aortic root diameter in hypertensive patients following stroke. Fifty-two hypertensive patients following stroke were divided into five stages according to Scheie's classification of hypertensive (H stage 0-4) and atherosclerotic (S stage 0-4) lesions by ophthalmologists. Arterial stiffness was measured as brachial-ankle pulse wave velocity (baPWV) using an automatic waveform analyzer. Aortic root diameter was measured using M-mode echocardiography. The H and S stages in retinal arteries correlated with each other (ρ = 0.443, p < 0.001). However, the S stage correlated with baPWV (ρ = 0.385, p = 0.005) and the aortic root diameter (ρ = 0.285, p = 0.043), while the H stage did not correlate with these parameters. Multiple stepwise regression analysis demonstrated that the aortic root diameter was independently associated with S stage (ß = 0.373, p = 0.006), even though baPWV was independently associated with neither S stage nor H stage. In conclusion, hypertensive lesions (H stage) in retinal arteries are associated with atherosclerotic lesions (S stage) in retinal arteries. However, S stage may reflect arterial stiffening and aortic root dilatation better than H stage in hypertensive patients following stroke. This difference between H and S stages of Scheie's classification should be kept in mind when considering the association between retinal microcirculation and large vessel arteriosclerosis.

Seasonal blood pressure variation and its relationship to environmental temperature in healthy elderly Japanese studied by home measurements.

The purpose of the present study was to examine seasonal blood pressure variation and its relationship to environmental temperature in healthy elderly Japanese, as studied by home measurements. Fifteen healthy elderly Japanese (79.3 +/- 5.9 yrs) measured their blood pressure at home each morning for more than 25 times per month for 3 years. Monthly mean outdoor temperatures were obtained from the Takamatsu meteorological Observatory. The highest levels of systolic and diastolic blood pressure measured at home were observed in February (129 +/- 14 and 81 +/- 13 mmHg). The lowest levels of systolic and diastolic blood pressure measured at home were observed in August (117 +/- 11 and 73 +/- 10 mmHg). Likewise, the lowest and highest means of outdoor temperature were observed in February (5.0 degrees C) and August (29.2 degrees C), respectively. Hence, both systolic and diastolic blood pressure demonstrated a close inverse correlation with the means of outdoor temperature (r = -0.973, p < 0.001 and r = -0.985, p < 0.001, respectively). A 1 degree C decrease in the mean outdoor temperature was associated with rises of 0.43 mmHg in systolic blood pressure (SBP) and 0.29 mmHg in diastolic blood pressure (DBP). Seasonal variations in home blood pressure and outdoor temperature showed complete correspondence in healthy elderly Japanese, with the blood pressures being inversely related to the ambient temperature. These seasonal home blood pressure variations should be kept in mind when controlling blood pressure in elderly patients.