Plasma cells and the chronic nonsuppurative destructive cholangitis of primary biliary cirrhosis

There has been increased interest in the role of B cells in the pathogenesis of primary biliary cirrhosis (PBC). Although the vast majority of patients with this disease have anti-mitochondrial antibodies, there is no correlation of anti-mitochondrial antibody titer and/or presence with disease severity. Furthermore, in murine models of PBC, it has been suggested that depletion of B cells may exacerbate biliary pathology. To address this issue, we focused on a detailed phenotypic characterization of mononuclear cell infiltrates surrounding the intrahepatic bile ducts of patients with PBC, primary sclerosing cholangitis, autoimmune hepatitis, chronic hepatitis C, and graft-versus-host disease, including CD3, CD4, CD8, CD20, CD38, and immunoglobulin classes, as well as double immunohistochemical staining for CD38 and IgM. Interestingly, CD20 B lymphocytes, which are a precursor of plasma cells, were found in scattered locations or occasionally forming follicle-like aggregations but were not noted at the proximal location of chronic nonsuppurative destructive cholangitis. In contrast, there was a unique and distinct coronal arrangement of CD38 cells around the intrahepatic ducts in PBC but not controls; the majority of such cells were considered plasma cells based on their expression of intracellular immunoglobulins, including IgM and IgG, but not IgA. Patients with PBC who manifest this unique coronal arrangement were those with significantly higher titers of anti-mitochondrial antibodies. CONCLUSION: These data collectively suggest a role for plasma cells in the specific destruction of intrahepatic bile ducts in PBC and confirm the increasing interest in plasma cells and autoimmunity.     

Silver oxide‐containing hydroxyapatite coating has in vivo antibacterial activity in the rat tibia

Bacterial infection is a serious postoperative complication of joint replacement. To prevent infections related to implantation, we have developed a novel antibacterial coating with Ag‐containing hydroxyapatite (Ag‐HA). In the present study, we examined the antibacterial activity of Ag‐HA implant coatings in the medullary cavity of rat tibiae. Forty 10‐week‐old rats received implantation of Ag‐HA‐ or HA‐coated titanium rods, then were inoculated with ～1.0 × 10² colony‐forming units of methicillin‐resistant Staphylococcus aureus. Bacterial counts were calculated for rats euthanized at 24, 48, and 72 h postoperatively. Serum levels of Ag (in the Ag‐HA group only) were calculated for rats euthanized at 24, 48, 72 h and 4 weeks. Radiographic evaluations of bone infection were also performed at 4 weeks. Tibiae from both groups showing infection were evaluated histologically. Significant differences in bacterial counts were seen at 24, 48, and 72 h. Mean concentrations of Ag in serum peaked about 48 h after implantation, then gradually decreased. Mean radiographic scores for infection were significantly lower with Ag‐HA implants than with HA implants. Histological examination showed better results for abscesses, bone resorption, and destruction of cortical bone around Ag‐HA‐coated implants. These results indicate that Ag‐HA coatings may help prevent surgical‐site infections associated with joint replacement. © 2013 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 31:1195–1200, 2013     

Immunohistochemically localization of vascular endothelial growth factor, vascular endothelial growth factor receptor-2, collagen I and fibronectin in the epithelia-mesenchymal junction of the human tooth germ

During tooth development, tooth shape is mediated by the ECM through epithelial-mesenchymal interactions mediated by the ECM at the epithelia-mesenchymal junction. Blood vessel endothelium growth is mainly regulated by vascular endothelial growth factor (VEGF) and the relationship between tooth shape formation and VEGF are unknown. We examined immunohistochemical localization of VEGF and its receptor VEGF receptor-2 (VEGFR-2), collagen I and fibronectin, (both representative protein of ECM) at the epithelia-mesenchymal junction of human deciduous teeth from the cap stage to late bell stages in a human fetus at 16, 20, 24, 28 and 32 weeks of gestation. Immunoreactivity at the basement membrane for VEGF was detected from the cap stage to the bell stage. Immunoreactivity to fibronectin was weak in the cap stage and increased in the bell stage; collagen I was negative in the cap stage and slightly expressed in the bell stage in the basement membrane. We suggest that VEGF and ECM affect cooperatively in tooth shape formation at the basement membrane.     

Stabilization Mechanism of Roxithromycin Tablets Under Gastric pH Conditions

Macrolide antibiotics are widely used at clinical sites. Clarithromycin (CAM), a 14-membered macrolide antibiotic, was reported to gelate under acidic conditions. Gelation allows oral administration of acid-sensitive CAM without enteric coating by hindering the penetration of gastric fluid into CAM tablets. However, it is unknown whether this phenomenon occurs in other macrolide antibiotics. In this study, we examined the gelation ability of 3 widely used macrolide antibiotics, roxithromycin (RXM), erythromycin A, and azithromycin. The results indicated that not only CAM but also RXM gelated under acidic conditions. Erythromycin A and azithromycin did not gelate under the same conditions. Gelation of RXM delayed the disintegration of the tablet and release of RXM from the tablet. Disintegration and release were also delayed in commercial RXM tablets containing disintegrants. This study showed that 2 of the 4 macrolides gelated, which affects tablet disintegration and dissolution and suggests that this phenomenon might also occur in other macrolides.     

Middle-preserving pancreatectomy with reversed pancreaticogastrostomy: report of a case

Parenchyma-sparing pancreatic resections have been reported increasingly in recent years; however, for multifocal diseases involving the head and the tail of the pancreas, total pancreatectomy is still the preferred procedure. The possible consequence of this procedure is loss of normal pancreatic parenchyma, resulting in insufficiency of pancreatic exocrine and endocrine functions. Various types of limited resection have been introduced for isolated or multiple pancreatic lesions, depending on the location of the tumor. Even for multifocal diseases, if the pancreatic body is spared, a middle-preserving pancreatectomy (MPP) can be performed to assure maximal pancreatic function and uncompromised quality of life. Yet, few papers have introduced the feasibility of MPP for a better outcome. This report describes a new surgical technique for MPP using an alternative approach for the remnant pancreas anastomosis. We used this technique successfully to remove a bifocal neoplasm: adenocarcinoma of the distal bile duct and mucinous cyst adenoma in the tail of the pancreas.     

Impact of Multivascular Disease on Cardiovascular Mortality and Morbidity in Patients Receiving Hemodialysis: Ten-Year Outcomes of the Q-Cohort Study

Aim: Multivascular disease, indicating concurrent arteriosclerotic lesions in a number of different vascular beds, is an independent risk factor for recurrent ischemic events in the general population. However, the impact of multivascular disease on the risk of developing cardiovascular disease has not been fully evaluated in patients receiving hemodialysis.Methods: A total of 3,504 hemodialysis patients were prospectively followed for 10 years. In this study, multivascular disease was defined as the coexistence of coronary artery disease and stroke. We examined the relationship between multivascular disease and the occurrence of composite cardiovascular endpoint, consisting of cardiovascular death, nonfatal coronary artery disease, nonfatal stroke, and peripheral artery disease.Results: The proportion of participants with multivascular disease was 5.7% (n = 200) at baseline. During follow-up (median, 106.6 months; interquartile range, 50.1–121.8 months), 1,311 patients experienced the composite endpoint, which was defined as at least one of the following: cardiovascular death (n = 620), nonfatal coronary artery disease (n = 318), nonfatal stroke (n = 340), and peripheral artery disease (n = 257). Compared with the group with no history of cardiovascular disease, the risk of experiencing the composite endpoint increased significantly with higher numbers of injured vascular beds in patients with single vascular disease (hazard ratio, 1.68; 95% confidence interval, 1.49–1.89) and in those with multivascular disease (hazard ratio, 2.11; 95% confidence interval, 1.71–2.60). In a multivariable analysis, multivascular disease was an independent predictor of cardiovascular events, in addition to diabetes, aging, and hypertension.Conclusions: This study clearly demonstrated that multivascular disease was a powerful predictor for cardiovascular mortality and morbidity in patients receiving hemodialysis.     

Magnesium sulphate infusion suppresses the cardiac release of noradrenaline during a handgrip stress test

BACKGROUND: Magnesium has several important cardiovascular effects, but its effect on cardiac sympathetic efferent neuron activity has not been clarified. Objectives: To examine the effect of magnesium sulphate infusion on cardiac sympathetic efferent postganglionic neuronal liberation of noradrenaline. PATIENTS AND METHODS: Twenty-two patients who underwent cardiac catheterization were randomly allocated to the control group or the magnesium group. Plasma noradrenaline and adrenaline concentrations in the aorta and the coronary sinus were measured. Noradrenaline or adrenaline release from the heart was calculated by dividing the difference in noradrenaline or adrenaline concentration between the aorta and the coronary sinus by that of the aorta. After baseline blood sampling, the control patients and the patients in the magnesium group received intravenous infusion of saline or magnesium sulphate (10 mmol). All patients were then subjected to 3 min of handgrip exercise stress test to augment sympathetic efferent neuronal activity, and the blood sampling was repeated. RESULTS: Although blood pressure was increased by the handgrip stress test, there were no differences in heart rate and blood pressure between the two groups, both at baseline and during the handgrip stress test. The plasma noradrenaline and adrenaline concentrations and noradrenaline or adrenaline release from the heart did not differ between the two groups in the baseline condition. However, the handgrip stress increased plasma noradrenaline concentrations and the cardiac noradrenaline release was increased in the control group, whereas the cardiac noradrenaline release was not increased by the handgrip stress in the magnesium group (P<0.02). CONCLUSIONS: These data indicate that magnesium sulphate infusion suppresses the release of catecholamines by the heart, which is an indirect index of sympathetic efferent neuronal activity.     

Diverse p53 gene aberration in hepatocellular carcinoma detected by dual-color fluorescence in situ hybridization

BACKGROUND AND AIM: In order to evaluate loss of the p53 gene more precisely, we performed dual-color fluorescence in situ hybridization (dual-color FISH) for chromosome 17 and p53 gene together with DNA polymorphism analysis of the p53 gene in hepatocellular carcinoma (HCC). METHODS: Dual-color FISH using probes specific for the centromere of chromosome 17 and the p53 gene was performed for 41 HCC and DNA polymorphism analysis was also performed for them. RESULTS: Of the 34 HCC tested by dual-color FISH, 20 had loss of at least one p53 gene (58.8%). In contrast, of the 32 HCC tested by DNA polymorphism analysis, 23 gave informative results, among which only eight had loss of heterozygosity (LOH) of the p53 gene (34.8%). Notably, among 14 cases positive for loss of the p53 gene by dual-color FISH, seven cases were negative for LOH of the p53 gene. Moreover, dual-color FISH revealed that the percentage of cells that lost at least one p53 gene increased as the HCC became less differentiated (P < 0.01), whereas LOH did not reveal any such correlation. CONCLUSIONS: These data suggest that loss of the p53 gene was present in a considerable number of HCC, and diversity of the p53 gene aberration increases with progression of HCC. Dual-color FISH is an effective method for detection of p53 gene aberration, and it can provide new insight into oncogenesis in HCC.