Expression of copper-transporting P-type adenosine triphosphatase (ATP7B) as a prognostic factor in human endometrial carcinoma

OBJECTIVE: Copper-transporting P-type adenosine triphosphate (ATP7B) has been reported to be associated with cisplatin resistance in vitro. However, the clinical significance of this transporter has not previously been addressed in endometrial carcinoma. Our goal was to investigate if ATP7B is expressed in endometrial carcinoma and whether its expression correlates with prognosis. METHODS: We performed immunohistochemical analysis of ATP7B using a monoclonal antibody against ATP7B in 51 endometrial endometrioid adenocarcinomas. 27 of 51 patients were treated with cisplatin-based chemotherapy after surgery. RESULTS: Cytoplasmic staining of tumor cells was observed in 37.3% (19/51 cases) of the analyzed carcinomas and no staining was observed in adjacent non-neoplastic cells. ATP7B positivity in the degree of differentiation of G2 and G3 carcinoma was significantly higher than that of G1 carcinoma (P = 0.019). The patients with ATP7B-positive tumors had a worse prognosis than that with ATP7B-negative tumors in overall survival and disease-free survival, respectively (P < 0.01). CONCLUSIONS: These findings suggest that overexpression of ATP7B expression in endometrial carcinoma is correlated with unfavorable clinical outcome in patients treated with cisplatin-based chemotherapy. ATP7B expression could be considered as a prognostic factor in patients with endometrial carcinoma.     

Association of Physical Performance and Pain With Fear of Falling Among Community—Dwelling Japanese Women Aged 65 Years and Older

Our aim was to explore the association of physical performance and pain with fear of falling among community-dwelling Japanese women.The subjects were 278 women aged 65 years and over. We collected information on fear of falling, painful joints, comorbidities, falls in the previous year, and cataracts. Walking time (distance of 6 m), chair stand time (5 times), grip strength, the timed up and go test (TUG), and functional reach were measured.The prevalence of fear of falling was 36.3%, and it increased with age, but it was not significant (P = 0.081). Multivariate logistic regression analysis showed that poor physical performance (longer walking time, longer chair stand time, weaker grip strength, and longer TUG) and pain (low back, and upper and lower extremity pain) were significantly associated with fear of falling after adjusting for age, body mass index, comorbidities, falls in the previous year, and cataracts.Maintaining physical functioning and managing pain may be important for elderly women with fear of falling.     

Advances in understanding and treating liver diseases during pregnancy:A review

Liver disease in pregnancy is rare but pregnancyrelated liver diseases may cause threat to fetal and maternal survival.It includes pre-eclampsia;eclampsia;haemolysis,elevated liver enzymes,and low platelets syndrome;acute fatty liver of pregnancy;hyperemesis gravidarum;and intrahepatic cholestasis of pregnancy.Recent basic researches have shown the various etiologies involved in this disease entity.With these advances,rapid diagnosis is essential for severe cases since the decision of immediate delivery is important for maternal and fetal survival.The other therapeutic options have also been shown in recent reports based on the clinical trials and cooperation and information sharing between hepatologist and gynecologist is important for timely therapeutic intervention.Therefore,correct understandings of diseases and differential diagnosis from the pre-existing and co-incidental liver diseases during the pregnancy will help to achieve better prognosis.Therefore,here we review and summarized recent advances in understanding the etiologies,clinical courses and management of liver disease in pregnancy.This information will contribute to physicians for diagnosis of disease and optimum management of patients.     

Effect of Alcohol Intake on the Efficacy of Interferon Therapy in Patients with Chronic Hepatitis C as Evaluated by Multivariate Logistic Regression Analysis

The effect of alcohol intake on the efficacy of interferon (IFN) therapy was evaluated retrospectively in patients with chronic hepatitis C diagnosed by liver histology and positive serum hepatitis C virus (HCV)-RNA. Patients included 119 given IFN therapy and 11 no IFN therapy. Serum HCV-RNA was measured 6 months after discontinuation of IFN therapy in 92 treated patients, 27.2% of whom showed disappearance of serum HCV-RNA. Multivariate logistic regression analysis revealed that this disappearance was affected by alcohol intake, the presence of its history ( p < 0.05) or cumulative alcohol consumption (kg) (p < 0.01), and serum HCV-RNA levels ( p < 0.001). The odds ratio associated with serum HCV-RNA still positive at 6 months was 7.016 (95% confidence interval: 1.444-34.082) and 1.004 (1.001-1.007) for the presence of alcohol intake history and the cumulative alcohol consumption, respectively. Other predictor variables–such as sex and age of patients, history of blood transfusion, HCV genotype, histological findings of the liver, and types of IFN– had no influence on the efficacy of the therapy. Cumulative alcohol consumption showed a negative correlation with serum HCV-RNA levels pretreatment, when the outcome variable was divided into two categories based on serum HCV-RNA levels: 10⁶ copy/ml or less and 10⁷ copy/ml or more. Alcohol intake was positively correlated with histological extent of alcoholic fibrosis, but affected neither grading nor staging of chronic viral hepatitis. We conclude that alcohol intake was a risk factor on the efficacy of IFN therapy in chronic hepatitis C patients. This effect was independent of serum HCV-RNA levels and histological findings specific for viral hepatitis in the liver.     

Successful treatment of gallbladder carcinoma producing alpha-fetoprotein with segmental adenomyomatosis

The successful treatment of hepatoid adenocarcinoma of the gallbladder with elevated serum alpha-fetoprotein (1243 ng/ml) and segmental adenomyomatosis in a 58-year-old woman is described. The woman had alpha-fetoprotein (AFP)-producing carcinoma of the gallbladder with regional lymph node metastasis and was treated by extended radical resection and postoperative adjuvant chemotherapy. She is alive, showing normal serum AFP concentration and no recurrence, 57 months after surgery. The tumor cells were stained immunohistochemically for AFP by the peroxidase anti-peroxidase method. Serum AFP reactivity to concanavalin A and lentil lectin was similar to the pattern shown in hepatocellular carcinoma. Only a few cases of AFP-producing gallbladder carcinoma have been reported and there have been no reports of long-term survivors. The combination of aggressive radical resection and chemotherapy seems to have been effective for achieving long-term survival without liver metastasis.     

Clinical Utility of Pulsed Doppler Flowmetry in Patients with Portal Hypertension

The recently developed Doppler flowmetry system that consists of an electronic sector and a pulsed Doppler flowmeter, is capable of determining the direction of blood flow in large veins visible by ultrasonography and measuring blood flow. It is noninvasive and can be performed in patients on ambulatory basis at the time of routine ultrasound examination. In this communication, clinical utility of pulsed Doppler flowmetry was tested in 20 patients with portal hypertension. Doppler flowmetry proved useful in differential diagnosis of splenorenal shunt and cystic disease, diagnosis of arterioportal shunt, diagnosis of portal vein occlusion, demonstration of hepatofugal flow in the splenic vein, and prediction of esophageal varices by the demonstration of hepatofugal flow in an enlarged left gastric vein.     

Differential production of Th1- and Th2-type chemokines by mouse Langerhans cells and splenic dendritic cells

Some chemokines specifically attract T helper 1 (Th1) cells, whereas others attract T helper 2 (Th2) cells. In this study, we investigated the capacity of Langerhans cells (LC) to produce Th1- and Th2-type chemokines in comparison with that of splenic CD11c(+) dendritic cells (DC). We prepared highly purified (>95%) LC from BALB/c mouse skin using the panning method. With regard to Th1-type chemokines, exogenous stimulus, such as interferon-gamma (IFN-gamma), lipopolysaccharide, or polyinosinic-polycytidylic acid, was mandatory for the production of substantial amounts of CXCL10, CXCL9, and CXCL11 both in LC and splenic DC. LC, as a whole, exhibited low ability to produce Th1-type chemokines in comparison with splenic DC. As for Th2-type chemokines, LC, but not splenic DC, produced high levels of CCL22 and CCL17 constitutively during culture even without exogenous stimuli. The production of Th2-type chemokines was regulated in a complicated manner. In particular, interleukin-4 upregulated, and IFN-gamma downregulated both CCL22 and CCL17 production by LC. Of note, LC produced much more amounts of Th2-type chemokines than splenic DC under any conditions tested. Finally, Th1- and Th2-type chemokines produced by LC were shown to be functional using chemokine receptor-transfected-2B4 T cells. The high production of CC chemokine receptor 4 ligands by LC in the absence of IFN-gamma may be an important character discriminating LC from other DC.     

Portal Hemodynamic Responses after Oral Intake of Glucose in Patients with Cirrhosis

Changes of portal, superior mesenteric, and splenic venous flows, and portohepatic gradient (portal vein pressure minus free hepatic vein pressure) after a meal were studied in patients with cirrhosis using the duplex ultrasonic Doppler flowmeter, and portal and hepatic vein catheterizations after ingestion of 227 ml of 33% glucose solution (300 kcal). As a control, changes of portal venous flow and portohepatic gradient after drinking 227 ml of water, were studied. Portal and superior mesenteric venous flows increased significantly at 30 min after glucose intake, and they returned gradually to the basal values, whereas no significant postprandial change occurred in splenic venous flow. The sum of superior mesenteric and splenic venous flows was greater than the estimated portal venous flow before glucose intake, and the difference widened during post-prandial mesenteric hyperemia, indicating an increase of blood flow into the portal-systemic shunts. After glucose intake, portohepatic gradient elevated immediately, in parallel with an increase of portal venous flow, and these changes persisted for the 30 min studied; however, no significant change occurred in these parameters after drinking water. In conclusion: 1) In patients with cirrhosis, hyperemia occurs in the intestine but not in the spleen after glucose intake, and 2) postprandial mesenteric hyperemia causes an increase of portal venous inflow, portal-systemic collateral flow, portal venous flow, and an elevation of portohepatic gradient.     

Brain ischemia and gastric mucosal damage in spontaneously hypertensive rats

Brain ischemia is often accompanied by acute gastric lesions. To clarify the underlying mechanism, the influence of acute ischemic insult to the brain on gastric hemodynamics and mucosal integrity was examined in spontaneously hypertensive rats. One hour after brain ischemia, gastric mucosal blood flow decreased to 71% of the preischemic levels in the control rats but was preserved significantly better, at 94 and 108%, in the prazosin-treated and guanethidine-treated rats, respectively. Vagotomy almost abolished the decrease in gastric mucosal blood flow during cerebral ischemia. Intragastric 0.6 N hydrochloric acid administered just after reperfusion induced more severe hemorrhagic ulcers in the control than in the prazosin-treated and vagotomized groups. These results suggest that noradrenergic neurons acting through ₁-adrenoceptors contributes to the decrease in gastric mucosal blood flow, and the subsequent disturbed integrity of the gastric mucosa, through the vagal adrenergic pathway during brain ischemia in spontaneously hypertensive rats.