Extrusion of penem antibiotics by multicomponent efflux systems MexAB-OprM,MexCD-OprJ,and MexXY-OprM of Pseudomonas aeruginosa

The high intrinsic penem resistance of Pseudomonas aeruginosa is due to the interplay among the outer membrane barrier, the active efflux system MexAB-OprM, and AmpC beta-lactamase. We studied the roles of two other efflux systems, MexCD-OprJ and MexXY-OprM, in penem resistance by overexpressing each system in an AmpC- and MexAB-OprM-deficient background and found that MexAB-OprM is the most important among the three efflux systems for extrusion of penems from the cell interior.     

The ovulation pattern during three consecutive menstrual cycles has a significant impact on pregnancy rate and sex of the offspring

Identification of the ovary at the time of ovulation during three consecutive menstrual cycles results in one of eight ovulation patterns, left-left-right, right-left-right, left-right-right, and right-right-right of right-sided ovulation and right-right-left, left-right-left, right-left-left, and left-left-left of left-sided ovulation. Our data suggest that IVF and IUI treatment in cycles in which development of the preovulatory follicle(s) occurs in the right-sided ovary-and ovulations took place from the left-sided ovary in the preceding two cycles (left-left-right)-is likely to show the best pregnancy potential and high offspring sex ratio.     

Relationship Between Mortality and Cancer‐Bearing Status in Patients With Chronic Kidney Disease Who Attended an Educational Program

Patients with malignancy have a poorer prognosis than others do, which must be taken into consideration when treating them for chronic kidney disease (CKD). However, there are few studies investigating their prognosis. This was an observational study of 515 (394 men and 121 women) stable non‐dialysis patients with CKD who attended a CKD educational program. Mean age was 68.8 ± 13.0 years. Median follow‐up was 968.5 days. Mean creatinine was 3.4 ± 1.6 mg/dL. Of these, 63 had malignancy and 452 did not; 20.6% of the former and 11.9% of the latter group died by the end of the study period (P = 0.0548). Malignancy was not associated with all‐cause mortality (HR: 1.3475, 95% CI: 0.7202–2.5214, P = 0.3507) but with malignancy‐associated mortality (HR: 3.9477, 95% CI: 1.6348–9.5331, P = 0.0023). Renal replacement therapy was not associated with mortality. Since malignancy greatly affects the prognosis, it must be taken into consideration when treating these patients.     

Selection of highly responsive T cell receptors by an analysis combining the expression of multiple markers

The clinical success of T cell receptor (TCR) gene–transduced T (TCR-T) cell therapy is expected as one of the next-generation immunotherapies for cancer, in which the selection of TCRs with high functional avidity (high-functional TCRs) is important. One widely used approach to select high-functional TCRs is a comparison of the EC50 values of TCRs, which involves laborious experiments. Therefore, the establishment of a simpler method to select high-functional TCRs is desired. We herein attempted to establish a simple method to select high-functional TCRs based on the expression of T cell activation markers using the mouse T cell line BW5147.3 (BW). We examined relationships between the EC50 values of TCRs in interleukin-2 production and the expression levels of TCR activation markers on BW cells. In TCR-expressing BW cells stimulated with antigenic peptides, the CD69, CD137, and PD-1 expression was differentially induced by various doses of peptides. An analysis of TCRs derived from the tumor-infiltrating lymphocytes of murine melanoma and peripheral blood T cells of hepatocellular carcinoma patients treated with a peptide vaccination revealed that an analysis combining CD69, CD137, and PD-1 expression levels in BW cells stimulated with a single dose of an antigenic peptide selected high-functional TCRs with functional avidity assessed by EC50 values. Our method facilitates the section of high-functional TCRs among tumor-reacting TCRs, which will promote TCR-T cell therapy. The stimulation of BW cells expressing objective TCRs with a single dose of antigenic peptides and analysis combining the expression of CD69, CD137, and PD-1 allows us to select highly responsive TCRs.