Indicators for early diagnosis of enterohemorrhagic Escherichia coli infection and methods for final diagnosis

Bloody diarrhea, abdominal cramp, history of barbecued beef for dinner at a restaurant and evidence of outbreak are important signs of Enterohemorrhagic Escherichia coli (EHEC) infections. Although early antibiotics therapy, such as fosfomycin and fluoroquinolones, is considered to be effective in Japan, stool cultures before antibiotics are essential for final diagnosis. In cases of hemorrhagic colitis or hemolytic uremic syndrome, when cultures are negative, detection of anti O-type specific lipopolysaccharides IgM antibodies is useful for estimate of causative EHEC. In our hospital, non-O157 EHECs increase in number as the causes of pediatric HUS since 1999.     

Attractant binding alters arrangement of chemoreceptor dimers within its cluster at a cell pole

Many sensory systems involve multiple steps of signal amplification to produce a significant response. One such mechanism may be the clustering of transmembrane receptors. In bacterial chemotaxis, where a stoichiometric His-Asp phosphorelay from the kinase CheA to the response regulator CheY plays a central role, the chemoreceptors (methyl-accepting chemotaxis proteins) cluster together with CheA and the adaptor CheW, at a pole of a rod-shaped cell. This clustering led to a proposal that signal amplification occurs through an interaction between chemoreceptor homodimers. Here, by using in vivo disulfide crosslinking assays, we examined an interdimer interaction of the aspartate chemoreceptor (Tar). Two cysteine residues were introduced into Tar: one at the subunit interface and the other at the external surface of the dimer. Crosslinked dimers and higher oligomers (especially a deduced hexamer) were detected and their abundance depended on CheA and CheW. The ligand aspartate significantly reduced the amounts of higher oligomers but did not affect the polar localization of Tar-GFP. Thus, the binding of aspartate alters the rate of collisions between Tar dimers in assembled signaling complexes, most likely due to a change in the relative positions or trajectories of the dimers. These collisions could occur within a trimer-ofdimers predicted by crystallography, or between such trimers. These results are consistent with the proposal that the interaction of chemoreceptor dimers is involved in signal transduction.     

Cytoplasmic Maspin Expression Correlates with Poor Prognosis of Patients with Adenocarcinoma of the Uterine Cervix

Background

Maspin is known to be a tumor suppressor protein and its prognostic significance in patients with several types of cancer has been reported. To date, however, no study has focused on the association between maspin expression and the prognosis of patients with adenocarcinoma of the uterine cervix. We explored the prognostic value of maspin expression with particular reference to its subcellular localization in patients with adenocarcinoma of the uterine cervix.

Methods

Paraffin-embedded tissue samples from 46 patients diagnosed as adenocarcinoma of the uterine cervix were immunohistochemically analyzed using an antibody for maspin. The patients were followed up for 3 to 165 months (median: 64.2 months) and the prognostic value was evaluated by the log-rank test and the Cox regression hazard model.

Results

A sample was considered maspin-positive if maspin was expressed in only the cytoplasm; 69.6% (32 cases) of the specimens were maspin-positive, and there was significant correlation between positivity and recurrence (P = 0.022). Maspin-positive patients had both shorter disease free survival and shorter overall survival by the log-rank test (P = 0.023, P = 0.043, respectively). By Cox’s multivariate analysis, the International Federation of Obstetrics and Gynecology (FIGO) status was the only independent prognostic factor for disease free survival and overall survival in patients with adenocarcinoma of the uterine cervix.

Conclusion

This is the first report to reveal an association between cytoplasmic maspin expression and the prognosis of patients with adenocarcinoma of the uterine cervix. Although further studies with a larger series of patients and a longer follow up period are necessary, the present results suggest that cytoplasmic maspin expression could be an indicator of unfavorable prognosis in patients with adenocarcinoma of the uterine cervix.     

Comparison of incretin immunoassays with or without plasma extraction: Incretin secretion in Japanese patients with type 2 diabetes

Aims/Introduction: The effectiveness of incretin‐based therapies in Asian type 2 diabetes requires investigation of the secretion and metabolism of glucose‐dependent insulinotropic polypepide (GIP) and glucagon‐like peptide 1 (GLP‐1). Plasma extractions have been suggested to reduce variability in intact GLP‐1 levels among individuals by removing interference that affects immunoassays, although no direct demonstration of this method has been reported. We have evaluated the effects of ethanol and solid‐phase extractions on incretin immunoassays. We determined incretin levels during meal tolerance tests in Japanese patients with type 2 diabetes and characterized predictors for incretin secretion. Materials and Methods: Japanese patients with type 2 diabetes (23 anti‐diabetic drug‐naïve and 18 treated with sulfonylurea [SU] alone) were subjected to meal tolerance tests, and incretin levels were determined by immunoassays with or without extraction. Results: Intact GLP‐1 levels determined by an intact GLP‐1 immunoassay with ethanol and solid‐phase extractions were lower than those determined without extraction. Intact GLP‐1 levels determined by the extractions were highly correlated with each other, much more so than the levels with and without extraction. Total GLP‐1 was unaffected by extractions, showing that extractions remove interference only in the case of intact GLP‐1. Incretin secretion after meal ingestion was similar between drug‐naïve and SU‐treated patients. Fasting and postprandial GLP‐1 levels were correlated positively with fasting free fatty acids and negatively with dipeptidyl peptidase‐4 activity. Conclusions: Ethanol and solid‐phase extractions remove interference for intact GLP‐1 immunoassay. SU showed little effect on incretin secretion. GLP‐1 and GIP secretion were predicted by different factors. (J Diabetes Invest, doi: 10.1111/j.2040‐1124.2011.00141.x, 2012)     

Mapping and ablation of clinical spontaneous perimitral atrial tachycardias using an ultra–high-resolution mapping system

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