Overexpression of cyclin‐dependent kinase 4 protein in extramammary Paget's disease

Cyclin‐dependent kinase 4 and 6 (CDK4/6) plays an important role in cell cycle progression, and the CDK4/6–cyclin D1 complex controls the cell cycle transition from G₁ phase to S phase. CDK4 is enhanced in several types of cancers and CDK4/6 inhibitors attenuate the proliferation of several types of cancer in vitro/in vivo. The purpose of our study was to investigate the expression pattern of CDK4 and evaluate its clinical importance in extramammary Paget's disease (EMPD). Almost all EMPD tissues were positive for CDK4, and metastatic lesions had a similar immunostaining intensity to primary lesions. In addition, CDK4 protein levels were positively correlated with those of cyclin D1 protein. Taken together, CDK4 may assume a crucial role in EMPD progression.     

Potential extraperitoneal space continuous with the peri-intestinal space: CT evidence and anatomical evaluation in patients with pneumatosis intestinalis without intestinal ischemia

Purpose  

Extraperitoneal spaces, such as the mesenteric space and the retroperitoneal space, can serve as areas that enable a reduction in the pressure exerted by extraperitoneal fluid collection and infiltrating diseases. In clinical practice, understanding the existence of these decompression spaces (or pathways) is very important for making accurate diagnoses. Here, we evaluated potential anatomical extraperitoneal spaces based on the extraluminal gas distribution in patients with pneumatosis intestinalis without intestinal ischemia.     

Effect of pravastatin on progression of coronary atherosclerosis in patients after coronary artery bypass surgery.

BACKGROUND: Although the anti-atherosclerotic effects of HMG-CoA reductase inhibitors are well known, their specific effect on saphenous vein grafts after coronary artery bypass graft (CABG) operation is not well documented and has not been studied in Japan, so the aim of the present prospective randomized controlled study involving 27 Japanese institutions was to investigate the effects of pravastatin on the progression of atherosclerosis in such grafts and native coronary arteries after CABG. METHODS AND RESULTS: A total of 303 patients who had undergone CABG were randomly assigned to either the pravastatin group (n =168) or the control group (n = 167). Paired coronary angiograms were obtained at baseline and at the end of 5-year follow-up in 182 (60%) patients. The low-density lipoprotein cholesterol concentration significantly decreased in the pravastatin group from 141.4 mg/dl to 113.7 mg/dl (-19.6%), compared with 141.1 mg/dl to 133.7 mg/dl (-5.2%) in the control group (p < 0.001). Although there was no significant difference in the quantitative coronary angiography measurements between the 2 groups, the global change score indicated a significant pravastatin-mediated reduction in plaque progression (p < 0.01). CONCLUSIONS: Pravastatin can potentially reduce atherosclerotic progression in both the bypass graft and native coronary arteries of patients after CABG.     

Relationships of oxidized HDL with blood coagulation and fibrinolysis in patients with type 2 diabetes mellitus

Although oxidization of LDL is known to be a crucial step for atherosclerotic progression, the significance of oxidized HDL remains to be clarified. The purpose of this study was to determine the relationships of oxidized HDL with blood coagulation and fibrinolysis in patients with diabetes. The subjects were outpatients with type 2 diabetes (n?=?163; median hemoglobin A1c, 6.9%). Activities of blood coagulation and fibrinolysis were evaluated by levels of thrombin–anti-thrombin complex (TAT) and plasmin–α2 plasmin inhibitor complex (PIC), respectively. Relationships of oxidized HDL with TAT and PIC were investigated by using linear regression analysis and logistic regression analysis. Oxidized HDL showed a significant inverse correlation with TAT and a marginally significant correlation with PIC (Spearman’s rank correlation coefficient: TAT, ??0.205 [p?<?0.01]; PIC, ??0.135 [p?=?0.087]). Prevalence of high TAT was significantly lower in the 3rd tertile group for oxidized HDL than in its 1st tertile (20.4 vs. 5.6%, p?<?0.05), and prevalence of high PIC was marginally significantly lower in the 3rd tertile group for oxidized HDL than in its 1st tertile (40.7 vs. 24.1%, p?=?0.099). In multivariate logistic regression analysis using age, gender, smoking, alcohol drinking, BMI, hemoglobin A1c, therapy for dyslipidemia, therapy for diabetes and anti-coagulation therapy as explanatory variables, odds ratios for high TAT and high PIC in the 3rd tertile group for oxidized HDL versus its 1st tertile group were significantly lower than the reference level of 1.00 (high TAT: 0.19 [0.04–0.99], p?<?0.05; high PIC: 0.33 [0.12–0.95], p?<?0.05). The frequency of high TAT or high PIC was lower in the higher tertile group for oxidized HDL than in its lower tertile group. Thus, oxidized HDL is thought to be inversely associated with both blood coagulation and fibrinolysis in patients with type 2 diabetes.     

Expression and regulation of periostin/OSF-2 gene in rat uterus and human endometrium

Periostin/OSF2 is a ligand for alphavbeta3 and alphavbeta5 integrins and activates the Akt/PKB pathway. Recent reports of periostin/OSF2 gene disrupted mice indicate that periostin/OSF-2 plays an important role in implantation. Quantitative RT-PCR revealed that the expression of periostin/OSF-2 mRNA in rat uteri was reduced to approximately 10% at 12 h after 17beta-estradiol (E2) injection, but was not changed after progesterone (P) injection. RT-PCR revealed the expression of periostin/OSF-2 in human endometrium, cultured human endometrial stromal cells (ESCs), and cultured human endometrial epithelial cells. In ESCs, the expression of periostin/OSF-2 mRNA was reduced to approximately 50% at 6 h after E2 treatment. The amount of periostin/OSF2 mRNA in human endometrium significantly increased during mid-proliferative and early secretory phases of menstrual cycle, and decreased during late-proliferative, mid-secretory and late secretory phases. The expression of periostin/OSF2 mRNA significantly decreased in ESCs decidualized by treatment with E2 and P for 7 and 11 days. By immunohistochemistry, the expression of periostin/OSF-2 was strongly detected in endometrial stromal cells during early proliferative, mid-proliferative and early secretory phases, and was strongly detected in endometrial epithelial cells during late secretory phase. This study demonstrated that the expression of periostin/OSF-2 is regulated by ovarian steroid hormones in rat uterus and human endometrium.     

Assessment of Hepatic Functional Reserve in Cirrhotic Patients by Computed Tomography of the Caudate Lobe

In order to investigate whether the size of thecaudate lobe of the cirrhotic liver is related to thehepatic functional reserve, the morphometric analysis ofthe caudate lobe was preformed retrospectively using computed tomography in 106 consecutivepatients of whom 67 had compensated (group 1), and 39uncompensated (group 2) liver cirrhosis. In 51 patients,hepatic measurements were repeated in follow-up. Age- and gender-matched controls were studied.The size of the caudate lobe and the ratio of thecaudate to right lobe were correlated with liverfunction. The caudate lobe was larger in the studypatients than in the controls, and larger in group 1than in group 2 (P < 0.01). The caudate to right loberatios were also greater in the study patientsespecially in group 1 (P < 0.01). In follow-up, the regression coefficient for the caudate to rightlobe ratio was positive in group 1 and negative in group2 (P < 0.05). Even though the caudate lobe ofpatients with uncompensated liver cirrhosis was larger than that of the controls, patients withcompensated liver cirrhosis had a larger caudate lobeand higher caudate to right lobe ratio compared to thepatients with uncompensated liver cirrhosis. The caudate lobe may have played an importantrole in maintaining proper liver function in thesepatients.     

Delayed Gastric Emptying by Helicobacter pylori Lipopolysaccharide in Conscious Rats

The present study was carried out to investigatethe possibility that lipopolysaccharide deprived fromHelicobacter pylori may alter gastric motility. Toaddress the question, we examined the effect of H. pylori lipopolysaccharide on gastricemptying in conscious rats. Gastric emptying wasevaluated by the phenol red method. Time-course anddose-related effects of intraperitoneal administrationof H. pylori lipopolysaccharide were investigated.Intraperitoneal injection of H. pylorilipopolysaccharide significantly suppressed gastricemptying of a liquid meal in a dose-dependent manner.The inhibitory action of H. pylori lipopolysaccharide wasobserved 2, 4, 8, or 12 hr after the injection. Theseresults suggest for the first time that H. pylorilipopolysaccharide may suppress gastric emptying in along-lasting fashion. It is also suggested that H. pylorimay influence gastric function through its cell wallstructure named lipopolysaccharide.     

Low-dose ethanol attenuates gut ischemia/reperfusion-induced liver injury in rats via nitric oxide production

BACKGROUND AND AIMS: The acute administration of low-dose ethanol was demonstrated to attenuate liver injury elicited by gut ischemia/reperfusion (I/R). Nitric oxide (NO) has been found to be a modulator of adhesive interactions between leukocytes, platelets, and endothelial cells, but there has been much controversy about the effects of ethanol on NO regulation. The objective of this study was to investigate the role of NO in ethanol-reduced hepatic microvascular dysfunction elicited by gut I/R. METHODS: Male Wistar rats were exposed to 30 min of gut ischemia followed by 60 min of reperfusion. Intravital microscopy was used to monitor leukocyte recruitment and non-perfused sinusoids (NPS). Plasma alanine aminotransferase (ALT) activities were measured 6 h after the onset of reperfusion. In another set of experiments, ethanol (10%, 1 g/kg) was administered before ischemia. RESULTS: Gut I/R elicited increases in the number of stationary leukocytes, NPS, and plasma ALT activities; all of which were attenuated by pretreatment with ethanol or an NO donor. Gut I/R caused the apoptosis of hepatocytes, which was prevented by pretreatment with ethanol. Pretreatment with an NO synthase inhibitor diminished the protective effects of ethanol. The administration of ethanol increased plasma nitrite/nitrate levels. CONCLUSION: These results suggest that low-dose ethanol attenuates the gut I/R-induced hepatic microvascular dysfunction and sequential liver injury by increasing sinusoidal NO levels.