LPS-CXCL10 Predicts Responses to Bortezomib in Myeloma Patients

To identify predictive biomarkers for clinical responses to bortezomib treatment, 0.06 mL of each whole blood without any cell separation procedures was stimulated ex vivo using five agents, and eight mRNAs were quantified. In six centers, heparinized peripheral blood was prospectively obtained from 80 previously treated or untreated, symptomatic multiple myeloma (MM) patients with measurable levels of M-proteins. The blood sample was procured prior to treatment as well as 2-3 days and 1-3 weeks after the first dose of bortezomib, which was intravenously administered biweekly or weekly, during the first cycle. Six stimulant-mRNA combinations; that is, lipopolysaccharide (LPS)-granulocyte-macrophage colony-stimulating factor (GM-CSF), LPS-CXCL chemokine 10 (CXCL10), LPS-CCL chemokine 4 (CCL4), phytohemagglutinin-CCL4, zymosan A (ZA)-GMCSF and ZA-CCL4 showed significantly higher induction in the complete and very good partial response group than in the stable and progressive disease group, as determined by both parametric (t-test) and non-parametric (unpaired Mann-Whitney test) tests. Moreover, LPS-induced CXCL10 mRNA expression was significantly suppressed 2-3 days after the first dose of bortezomib in all patients, as determined by both parametric (t-test) and non-parametric (paired Wilcoxon test) tests, whereas the complete and very good partial response group showed sustained suppression 1-3 weeks after the first dose. Thus, pretreatment LPS-CXCL10 mRNA and/or the six combinations may serve as potential biomarkers for the response to bortezomib treatment in MM patients

Fretting fatigue behaviour of Ni-free high-nitrogen stainless steel in a simulated body fluid

Fretting fatigue behaviour of Ni-free high-nitrogen steel (HNS) with a yield strength of about 800 MPa, which was prepared by nitrogen gas pressurized electroslag remelting, was studied in air and in phosphate-buffered saline (PBS(-)). For comparison, fretting fatigue behaviour of cold-rolled SUS316L steel (SUS316L(CR)) with similar yield strength was examined. The plain fatigue limit of HNS was slightly lower than that of SUS316L(CR) although the former had a higher tensile strength than the latter. The fretting fatigue limit of HNS was higher than that of SUS316L(CR) both in air and in PBS(-). A decrease in fatigue limit of HNS by fretting was significantly smaller than that of SUS316L(CR) in both environments, indicating that HNS has better fretting fatigue resistance than SUS316L(CR). The decrease in fatigue limit by fretting is discussed taking into account the effect of friction stress due to fretting and the additional influences of wear, tribocorrosion and plastic deformation in the fretted area

A case of Hirschsprung's disease underwent surgery in adulthood

Adult Hirschsprung's disease is a rare motor disorder of the gut that is frequently misdiagnosed as refractory constipation. We describe a 30-year-old patient with adult Hirschsprung's disease with a history of chronic constipation requiring daily enema. Barium enema and rectal biopsy showed short segment-type Hirschsprung's disease with a grossly distended sigmoid colon with fecal retention. Staged operations, including the Duhamel-GIA method as a definitive surgery, completely resolved the patient's symptoms. There were no complications by the end of a 7-year follow-up. Adult Hirschsprung's disease should be considered in the differential diagnosis of cases where adult patients present with chronic constipation. Despite technical difficulty of the modified Duhamel-GIA procedure due to chronic fibrous changes of the rectum, it is a feasible surgical option for treating cases of adult Hirschsprung's disease