Manubriosternal subluxation/dislocation can lead to manubriosternal septic arthritis in patients with kyphoscoliosis

Locally deranged joint anatomy can predispose to septic arthritis which can be managed by surgical debridement. We present a case of manubriosternal subluxation/dislocation caused by kyphoscoliosis leading to manubriosternal septic arthritis.     

Effects of repeated subculturing and prolonged storage at room temperature of enterohemorrhagic Escherichia coli O157:H7 on pulsed-field gel electrophoresis profiles

Three clinical strains of enterohemorrhagic Escherichia coli O157:H7 which were subcultured repeatedly or stored at room temperature over a 25-week period showed appreciable variations in their pulsed-field gel electrophoresis fragment patterns. The variations could be explained by a couple of spontaneous genetic events at most and thus did not invalidate the genetic lineage of the strains.     

Peroxynitrite modulates release of inflammatory mediators from guinea pig lung mast cells activated by antigen-antibody reaction

BACKGROUND: Peroxynitrite (ONOO-), the product of the reaction between the superoxide anion (*O2-) and nitric oxide (NO), is produced during inflammatory disease and may be a major cytotoxic agent. No reports are available as to whether ONOO- generates or modulates inflammatory mediator release from activated guinea pig lung mast cells. In this study, we explored the modulatory role of intracellular ONOO- on inflammatory mediator release (histamine and leukotrienes) from activated mast cells. METHODS: Guinea pig lung mast cells were purified by the enzyme digestion, and by using the rough and discontinuous Percoll density gradients. Mast cells were sensitized with IgG1 (anti-ovalbumin) antibody and challenged with ovalbumin (OVA). The intracellular ROS formation was determined by following the oxidative production of 2', 7'-dichlorofluorescein diacetate (DCFH-DA), dihydrorhodamine 123 (DHR), and anti-nitrotyrosine antibody immunofluorescence. Histamine was assayed using a fluorometric analyzer, leukotrienes by radioimmunoassay, intracellular Ca2+ levels by confocal scanning microscopy, and PLA(2) activity using prelabeling of [3H]arachidonic acid. RESULTS: ROS detected by DCFH-DA weakly increased in mast cells activated with OVA (1.0 g/ml), and the ROS so generated was inhibited by ebselen (50 microM). However, the ROS detected by DHR increased 3-fold under the same conditions. Peroxynitrite scavengers sL-MT, DMTU, and inhibitor FeTPPS inhibited ROS formation but the NADPH oxidase inhibitor diphenyleneiodonium (DPI) only partially inhibited this formation. Dimethyl thiourea (DMTU) and seleno-L-methionine (sL-MT) inhibited the tyrosine nitration of cytosolic proteins, the release of histamine and leukotrienes, Ca2+ influx, and the PLA(2) activity evoked by mast cell activation. CONCLUSION: The data obtained suggests that the ROS generated by the antigen/antibody reaction activated mast cells is ONOO-, and that this modulates the release of inflammatory mediators via Ca2+ -dependent PLA(2) activity.     

CDX2 and MUC2 protein expression in extrahepatic bile duct carcinoma

Although CDX2-mediated intestinal metaplasia and its association with gastric and esophageal carcinoma have been well described, its function in extrahepatic bile duct (EBD) carcinoma remains unclear. CDX2 and MUC2 expression were examined in 193 EBD carcinomas, and observed in 37.3% and 42.0%, respectively. Both CDX2 and MUC2 were observed in 27.4%. CDX2 (P<.001) and MUC2 (P<.001) were correlated with histologic subtypes and present, respectively, in all intestinal-type adenocarcinomas and mucinous carcinomas, 12 (71%) and 13 (76%) of 17 papillary carcinomas, 2 (40%) and 2 (40%) of 5 adenosquamous carcinomas, and 28.4% and 33.5% of adenocarcinomas, not otherwise specified. CDX2 was observed more frequently in tumors with papillary growth (P=.03) and no vascular invasion (P=.04), whereas MUC2 was more common in cases with low stage (P=.01) and no vascular invasion (P<.001). Patients with CDX2+/MUC2+ tumors had significantly better overall survival in univariate but not multivariate analysis than patients with other tumors (P<.05). Expression of CDX2 and MUC2 supports that intestinal differentiation is present in specific subtypes of EBD carcinomas, and their expression status correlates with patients' overall survival.     

Distribution of mutations in the PEX gene in families with X-linked hypophosphataemic rickets (HYP)

Mutations in the PEX gene at Xp22.1 (phosphate-regulating gene with homologies to endopeptidases, on the X-chromosome), are responsible for X-linked hypophosphataemic rickets (HYP). Homology of PEX to the M13 family of Zn2+ metallopeptidases which include neprilysin (NEP) as prototype, has raised important questions regarding PEX function at the molecular level. The aim of this study was to analyse 99 HYP families for PEX gene mutations, and to correlate predicted changes in the protein structure with Zn2+ metallopeptidase gene function. Primers flanking 22 characterised exons were used to amplify DNA by PCR, and SSCP was then used to screen for mutations. Deletions, insertions, nonsense mutations, stop codons and splice mutations occurred in 83% of families screened for in all 22 exons, and 51% of a separate set of families screened in 17 PEX gene exons. Missense mutations in four regions of the gene were informative regarding function, with one mutation in the Zn2+-binding site predicted to alter substrate enzyme interaction and catalysis. Computer analysis of the remaining mutations predicted changes in secondary structure, N-glycosylation, protein phosphorylation and catalytic site molecular structure. The wide range of mutations that align with regions required for protease activity in NEP suggests that PEX also functions as a protease, and may act by processing factor(s) involved in bone mineral metabolism.      

Bacillus Calmette-Guerin Granuloma in Seminal Vesicle: Report of the First Case in the English Literature

A 64-year-old man underwent a radical cystoprostatectomy for intravesical bacillus Calmette-Guerin (BCG) therapy-resistant, recurrent muscle invasive transitional cell carcinoma (TCC) of the urinary bladder. He had a history of left radical nephroureterectomy for a papillary TCC of the left ureter 10 months ago. On microscopic examination, not only multifocal residual papillary TCCs in the urinary bladder but also multiple small granulomas in the urinary bladder and prostate were noted. Interestingly, unusually severe granulomatous inflammation accompanying focal central caseating necrosis was identified in the subepithelial tissue of the left seminal vesicle and vas deferens. Neither prostatic adenocarcinoma nor TCC involvement was identified in the prostate and seminal vesicles. A few acid-fast bacilli were identified by the Ziehl-Neelsen staining in the seminal vesicle granulomas, confirming the BCG-induced inflammation. To the best of our knowledge, this is the first case of BCG-induced granuloma involving the seminal vesicle. It is uncertain why only the left seminal vesicle was involved with BCG granulomas and the incidence and mechanism of seminal vesicle BCG granuloma await more cases.