Deficiency in EBV-induced gene 3 (EBI3) in MRL/ lpr mice results in pathological alteration of autoimmune glomerulonephritis and sialadenitis

MRL/lpr mice develop a systemic autoimmune disease that is reminiscent of systemic lupus erythematosus (SLE) and Sjögren’s syndrome in humans. To investigate the role of IL-27 in the development of autoimmune disorders in MRL/lpr mice, we disrupted the EBV-induced gene 3 (EBI3), which is a subunit of IL-27. Consequently, the pathophysiology of glomerulonephritis and sialadenitis, which develops in MRL/lpr mice, was drastically changed. EBI3^?/? MRL/lpr mice developed disease that resembles human membranous glomerulonephritis (MGN), not diffuse proliferative glomerulonephritis (DPGN), with a predominance of IgG1 in glomerular deposits, and different type sialadenitis from Sjögren’s syndrome, with IgG1 producing plasma cell infiltration in salivary glands, accompanied by increased IgG1 and IgE in the sera. T cells in these mice displayed significantly reduced IFN-γ production along with elevated IL-4 expression. Loss of EBI3 thus favors Th2-type autoimmune responses, suggesting that the Th1/Th2 balance may be a pivotal determinant of phenotypes of human autoimmune diseases.     

The effect of PGI2 analogue on vascular endothelial function and platelet aggregation in patients with NIDDM

The effect of the short-term administration of beraprost sodium, an analogue of prostaglandin I₂ (PGI₂), on the function of vascular endothelial cells and platelet in non-insulin-dependent diabetes mellitus (NIDDM) patients was investigated. Seven nonobese NIDDM patients with microalbuminuria were recruited for this study. They received a dose of 20 μg of beraprost sodium three times daily for 1 month. Before and after this treatment, various factors concerning functions of vascular endothelial cells and platelet were measured. Treatment with PGI₂ analogue caused a decrease in basal levels of plasma lipoprotein (a) from 16.8 ± 5.3 to 13.2 ± 4.4 mg/dL (p < 0.05), immunoreactive-(i-)endothelin from 2.4 ± 0.3 to 1.6 ± 0.2 pg/mL, and i-thrombomudulin from 9.3 ± 3.7 to 7.9 ± 3.0 FU/L, respectively, and caused a significant increase in basal plasma i-tissue type plasminogen activator (tPA) from 5.3 ± 0.7 to 8.3 ± 1.5 ng/mL (p < 0.01). This treatment also increased maximum response of i-tPA induced by desmopressin infusion. Platelet aggregation due to ADP was inhibited in five of six patients after this treatment. In conclusion, treatment with PGI₂ analogue caused a decrease in the presumed promoting factors of angiopathy such as lipoprotein (a) and endothelin and an increase in the protecting endothelial factor of angiopathy, tissue type plasminogen activator in patients with NIDDM. And immunoreactive thrombomodulin levels which reflect the vascular endothelial cell injury tended to decrease with the treatment. Therefore, it is suggested that this treatment preserves the vascular endothelial function in diabetes.     

A microRNA regulatory mechanism of osteoblast differentiation

Growing evidence shows that microRNAs (miRNAs) regulate various developmental and homeostatic events in vertebrates and invertebrates. Osteoblast differentiation is a key step in proper skeletal development and acquisition of bone mass; however, the physiological role of non-coding small RNAs, especially miRNAs, in osteoblast differentiation remains elusive. Here, through comprehensive analysis of miRNAs expression during osteoblast differentiation, we show that miR-206, previously viewed as a muscle-specific miRNA, is a key regulator of this process. miR-206 was expressed in osteoblasts, and its expression decreased over the course of osteoblast differentiation. Overexpression of miR-206 in osteoblasts inhibited their differentiation, and conversely, knockdown of miR-206 expression promoted osteoblast differentiation. In silico analysis and molecular experiments revealed connexin 43 (Cx43), a major gap junction protein in osteoblasts, as a target of miR-206, and restoration of Cx43 expression in miR-206-expressing osteoblasts rescued them from the inhibitory effect of miR-206 on osteoblast differentiation. Finally, transgenic mice expressing miR-206 in osteoblasts developed a low bone mass phenotype due to impaired osteoblast differentiation. Our data show that miRNA is a regulator of osteoblast differentiation.     

Outcome of MR-guided percutaneous cryoablation for hepatocellular carcinoma

Purpose

To assess the mid-term results of MR-guided percutaneous cryoablation for small hepatocellular carcinoma (HCC).

Methods

Using an argon-based cryoablation system, MR-guided percutaneous cryoablation was performed. The number of tumors was three or fewer. The maximum diameter of tumors was less than 5 cm when solitary and no more than 3 cm when multiple. The Kaplan–Meier method was used to calculate the survival of patients.

Results

Among 15 patients, 16 tumors were treated. The maximum tumor diameter ranged from 1.2 to 4.5 cm, with a mean of 2.5 ± 0.8 cm (mean ± standard deviation). The volume of iceballs measured on MR-images was greater than that of the tumors in all cases. The follow-up period ranged from 10 to 52 months, with a mean of 36.6 ± 12.1 months. One-year and 3-year overall survival were 93.8 and 79.3%, respectively. The complete ablation rate was 80.8% at 3 years. Immediate complications were pneumothorax, hemothorax, and pleural effusion. An ablation zone was not absorbed and content exuded from a scar of the probe tract 4 months after cryoablation in one patient.

Conclusion

MR-guided percutaneous cryoablation appears to be a feasible modality and potentially good option for the treatment of small HCC.

     

Xanthogranulomatous cholecystitis: the use of preoperative CT findings to differentiate it from gallbladder carcinoma

Background and aim

A retrospective analysis was performed on 32 patients with histologically confirmed xanthogranulomatous cholecystitis (XGC) and 21 patients with gallbladder carcinoma who underwent surgical treatment between 1998 and 2007.

Methods

All patients underwent preoperative CT scanning. The CT features analyzed were: the presence of intramural hypoattenuated nodules or bands, mucosal line, the patterns of wall thickening and enhancement, and the presence of stones in the gallbladder. The variables of the CT findings with XGC were analyzed using multivariate logistic regression analysis.

Results

Intramural hypoattenuated nodules were observed in 21 patients (65%) with XGC, but in only six patients (29%) with gallbladder carcinoma (P < 0.01). The mucosal line was observed in 27 patients (84%) with XGC and in only four patients (19%) with gallbladder carcinoma (P < 0.0001). Gallstones were noted in 24 patients (75%) with XGC and five patients (24%) with gallbladder carcinoma (P < 0.001). There was no significant difference in the pattern of gallbladder wall thickening (diffuse or focal) and the presence of changes outside the gallbladder. Multivariate logistic regression analysis revealed from the CT features that the enhanced continuous mucosal line (P = 0.0013) and the presence of gallstones (P = 0.0072) were independently correlated with XGC.

Conclusion

CT features of the enhanced continuous mucosal line in a thickened gallbladder wall, together with gallstones in a patient with chronic gallbladder disease, are highly suggestive of XGC. Accurate diagnosis of XGC may therefore indicate the need to select a less aggressive surgical approach.     

Papillary dilation vs sphincterotomy in endoscopic removal of bile duct stones a randomized trial with manometric function

To circumvent the long-term effects of papillary ablation for extracting common bile duct stones (<12 mm in diameter) in endoscopic sphincterotomy (EST), endoscopic papillary dilation (EPD) was attempted in 20 patients. To evaluate papillary function before and after the procedures, manometry of the sphincter of Oddi was carried out in 13 with EPD and 10 of 20 patients with EST. Extraction of all stones was successful (100%) in both groups at an equal rate. Repeated numbers of procedures were common in both groups. However, the mean duration of the procedure was high in EPD compared to EST (63 min vs 42 min,P<NS). Adjunctive therapies like mechanical lithotripsy (ML), nasobiliary drainage, and choledochoscopy were included in EPD, while EST required a basket catheter and ML. There was no significant difference on manometry before and after the procedures (P=NS), although papillary function was found to have decreased after the EPD. In contrast, all patients in the EST group lost papillary function after the procedure. Thirty-day morbidity and mortality rate were absent in both groups. Immediate and 2.5-year follow up complications were uncommon in both groups. As a simple method, EPD may be an effective and safe alternative to EST in the management of patients with bile duct stones who require maintenance of papillary function.     

A prospective study on the prognostic significance of urokinase-type plasminogen activator levels in breast cancer tissue

Urokinase-type plasminogen activator (u-PA), which cleaves plasminogen to yield plasmin, is a serine protease of fibrinolysis and is presumed to play a key role in extracellular proteolysis and facilitate the migration of cancer cells. This study was conducted prospectively to evaluate the prognostic significance of u-PA antigen level in breast cancer tissues. u-PA concentrations in the cytosol of 226 breast cancer tissues were determined prospectively by enzyme-linked immunosorbent assay using cytosol fractions prepared for steroid hormone assay. The median follow-up period of the patients was 60 months. Various prognostic factors were evaluated by univariate analysis or multivariate analysis using the Cox proportional-hazards method. Patients with primary breast cancer containing high levels of u-PA had a significantly shorter disease-free survival than patients with low levels of u-PA antigens. In multivariate analysis, a high level of u-PA was an independent risk factor for disease-free survival, being independent of age, axillary node status, and estrogen receptor status. Among the major prognostic factors, a high u-PA antigen level, lymph node involvement, and a positive estrogen receptor status were the most important for predicting relapse-free survival (P=0.044, P<0.0001, P=0.0039). This first prospective study confirmed the prognostic significance of the u-PA antigen level in association with other major prognostic factors. The results of our present study suggest that u-PA in breast cancer tissue might be involved in breast cancer invasion and metastasis. Received: 20 November 1996 / Accepted: 9 June 1997     

Determination of Hepatitis Delta Virus (HDV)-RNA in Asymptomatic Cases of HDV Infection

Objectives: To assess the frequency of hepatitis delta virus (HDV) viremia in asymptomatic cases of HDV infection and the clinical significance of the HDV viremia, we conducted a cross-sectional community-based study. Methods : Of 2207 examinees, 210 (9.5%) were found to be positive for hepatitis B surface antigen (HBsAg). Antibody to HDV was detected in 47 (22.4%) of the 210 examinees, and 43 of the 47 were further evaluated for serum HDV-RNA by polymerase chain reaction. Results : Twenty-one (48.8%) of the 43 had detectable levels of HDV-RNA in serum, and 22 (51.2%) were negative for serum HDV-RNA. The majority (61.9%) of the HDV-RNA-positive HBsAg carriers had high levels of serum ALT. In contrast, the frequency of an abnormally high level of serum ALT was only 9.1% in the HBsAg carriers positive for HDV antibody but negative for HDV-RNA and the frequency did not differ from that seen in the HBsAg-negative individuals. The semi-quantified HDV-RNA levels did not correlate with the serum ALT levels. Conclusion : Seropositivity of HDV-RNA was strongly associated with liver cell damage, even in asymptomatic cases. The absence of a detectable level of serum HDV-RNA might be related to previous HDV infection.