ABO‐incompatible living kidney transplantation (ABO‐ILKT) has steadily become more widespread. However, the optimal immunosuppressive regimen for ABO‐ILKT remains uncertain. We aimed to determine the ...longitudinal changes in the outcomes from ABO‐ILKT compared with those from ABO‐compatible living kidney transplantation (ABO‐CLKT) over the last 25 years. Of 1195 patients who underwent living kidney transplantations (LKT) at our institute between 1989 and 2013, 1032—including 247 ABO‐ILKT and 785 ABO‐CLKT cases—were evaluated for graft survival, patient survival, infectious adverse events, and renal function. The patients were divided into four groups according to the transplantation era and ABO‐compatibility. In the past decade, ABO‐ILKT and ABO‐CLKT recipients yielded almost equivalent outcomes with respect to the 9‐year graft survival rates, which were 86.9% and 92.0%, respectively (hazard ratio HR 1.38, 95% confidence interval CI 0.59–3.22, p = 0.455). The graft survival rate for ABO‐ILKT conducted between 2005 and 2013 was better than that for ABO‐ILKT conducted between 1998 and 2004 (HR 0.30, 95% CI 0.13–0.72, p = 0.007). ABO‐ILKT recipients showed substantial improvements in the graft survival rate over time. Graft survival was almost identical over the past decade, regardless of ABO‐incompatibility. Currently, ABO‐ILKT is an acceptable treatment for patients with end‐stage renal disease.
The authors determine the longitudinal changes in the outcomes from ABO‐incompatible living kidney transplantation over the last 25 years and conclude that ABO‐incompatible living kidney transplant recipients have experienced substantial improvements in graft survival rate, frequency of infectious adverse events, and renal function over time.
Background
In the tumor microenvironment, factors inhibiting the targeting of cancer cells by activated T cells have recently been noted. B7-H3 belongs to the B7 superfamily of immune regulatory ...ligands and plays an important role in the adaptive immune response of co-inhibitory/stimulatory factors in regulating T cells. However, the degree to which B7-H3 directly affects tumor immune evasion mechanisms remains unclear, particularly in patients with breast cancer. Regulatory T cells (Tregs) are known as a key player in the inhibition of immune mechanisms. The present study demonstrated that expression of B7-H3 on tumor cells and the number of Tregs in the tumor microenvironment independently affected prognosis in breast cancer patients.
Methods
We immunohistochemically investigated the presence of B7-H3 and forkhead box P3 (Foxp3)-positive Tregs in pathological specimens from 90 patients with breast cancer.
Results
Positive B7-H3 expression was associated with shorter recurrence-free survival (RFS) (
p
=
0.014). A higher percentage of Foxp3-positive cells also correlated with shorter RFS (
p
=
0.039). Multivariate analysis showed B7-H3 as an independent factor on RFS. Foxp3 expression in tumor-infiltrating lymphocytes (TILs) correlated significantly with larger tumor size (>2 cm), expression of human epidermal growth factor receptor 2 (HER2), and higher nuclear grade (
p
=
0.003,
p
<
0.001,
p
=
0.001, respectively). No correlation was identified between expression of B7-H3 and the percentage of Foxp3-positive TILs.
Conclusions
B7-H3 and Foxp3 can be regarded as markers of poor prognosis in breast cancer. These expressions were not correlated, suggesting that B7-H3 expression plays an independent role in tumor immune evasion, regardless of Tregs.
Costimulatory signals are required for activation of immune cells, but it is not known whether they contribute to other biological systems. The development and homeostasis of the skeletal system ...depend on the balance between bone formation and resorption. Receptor activator of NF-κB ligand (RANKL) regulates the differentiation of bone-resorbing cells, osteoclasts, in the presence of macrophage-colony stimulating factor (M-CSF). But it remains unclear how RANKL activates the calcium signals that lead to induction of nuclear factor of activated T cells c1, a key transcription factor for osteoclastogenesis. Here we show that mice lacking immunoreceptor tyrosine-based activation motif (ITAM)-harbouring adaptors, Fc receptor common γ subunit (FcRγ) and DNAX-activating protein (DAP)12, exhibit severe osteopetrosis owing to impaired osteoclast differentiation. In osteoclast precursor cells, FcRγ and DAP12 associate with multiple immunoreceptors and activate calcium signalling through phospholipase Cγ. Thus, ITAM-dependent costimulatory signals activated by multiple immunoreceptors are essential for the maintenance of bone homeostasis. These results reveal that RANKL and M-CSF are not sufficient to activate the signals required for osteoclastogenesis.
We have measured x-ray diffraction and small-angle x-ray scattering of fluid rubidium by reducing electron density down to the range where the compressibility of the interacting electron gas has been ...theoretically predicted to become negative. Negative compressibility is closely associated with a negative value of the static dielectric function, which makes the screened Coulomb interaction among like charges overall attractive. It was clearly observed that the interatomic distance decreases in spite of the fact that mean interatomic distance increases with expansion, suggesting that an attractive interaction among like charges, ions in this case, is enhanced. These findings indicate that the observed structural features are evidence of the compressional instability of the 3D electron gas.
Photodamaged skin exhibits wrinkles, pigmented spots, dryness and tumors. Solar UV radiation induces cyclobutane pyrimidine dimers (CPD) and further produces base oxidation by reactive oxygen species ...(ROS). ROS are thought to be a major factor to initiate the up‐regulation of matrix metalloproteinases (MMPs) in keratinocytes and fibroblasts via activation of receptor proteins on the cell membrane of keratinocytes and fibroblasts, and to degrade fiber components in dermis, leading to wrinkle formation.
Coenzyme Q10 (CoQ10) was reported to reduce ROS production and DNA damage triggered by UVA irradiation in human keratinocytes in vitro. Further, CoQ10 was shown to reduce UVA‐induced MMPs in cultured human dermal fibroblasts. We speculated that UVB radiation‐induced cytokine production in keratinocytes may be inhibited by CoQ10, resulting in the reduction of MMPs in fibroblasts leading to wrinkle reduction. Our in vitro studies showed that UVB‐induced IL‐6 production of normal human keratinocyte (NHKC) decreased in the presence of CoQ10. Furthermore, MMP‐1 production of fibroblasts cultured with the medium containing CoQ10 collected from UVB‐irradiated NHKC significantly decreased during 24 h culture. In the clinical trial study, we found that the use of 1% CoQ10 cream for five months reduced wrinkle score grade observed by a dermatologist. Taken together, our results indicate that CoQ10 may inhibit the production of IL‐6 which stimulate fibroblasts in dermis by paracrine manner to up‐regulate MMPs production, and contribute to protecting dermal fiber components from degradation, leading to rejuvenation of wrinkled skin.
Inelastic x-ray scattering spectra of fluid S were measured from 403 K near the melting point to 1343 K in the supercritical region at 25 MPa. Although the dynamic structure factor in the ...supercritical region exhibits a single peak profile, the spectrum includes collective inelastic excitations besides the quasielastic component. The acoustic excitation energy in the supercritical region is close to the one predicted by the sound speed in the fluid consisting of S8 molecules and the observed excitation energies of the stretching modes in S molecules suggest that few fraction of S2 molecules in the supercritical region near the liquid-vapor critical point. This result indicates that the nearest neighbor coordination number in the supercritical fluid S obtained by x-ray diffraction Inui et al., J. Phys. Conf. Ser. 98 (2008) 012008 was underestimated.
•The dynamic structure factor of fluid sulfur was obtained up to 1343 K and 25 MPa in the supercritical region.•The inelastic excitations arising from molecular vibrational modes are observed.•Few fractions of S dimmers among S molecules in the supercritical region are estimated.
Abstract Background The purpose of this study was to present our experience with robot-assisted radical prostatectomy (RARP) for localized prostate cancer in renal transplant recipients (RTRs) and to ...determine the feasibility and efficacy of RARP in these patients. Methods We retrospectively reviewed the medical records of 236 patients who underwent RARP for localized prostate cancer at our institution between August 2011 and July 2015 and identified 3 patients who were RTRs. We reviewed the available clinical data of the 3 patients. Results All patients underwent RARP successfully without any major complications. The mean operation time was 162 minutes (range, 127–195 minutes). The mean estimated blood loss was 52 mL (range, 30–75 mL); therefore, the patients did not need any perioperative blood transfusion. In all cases, graft function, as determined according to the serum creatinine level, was stable during and after the operation. Pathological examination showed negative surgical margins with organ-confined disease in all patients. Conclusions We reported 3 RTRs with localized prostate cancer who were treated with RARP. RARP might be a feasible and effective minimally invasive technique for the treatment of localized prostate cancer in carefully selected RTRs.
The transverse acoustic excitation modes were detected by inelastic x-ray scattering in liquid Ga in the Q range above 9 nm(-1) although liquid Ga is mostly described by a hard-sphere liquid. An ab ...initio molecular dynamics simulation clearly supports this finding. From the detailed analysis for the S(Q,omega) spectra with a good statistic quality, the lifetime of 0.5 ps and the propagating length of 0.4-0.5 nm can be estimated for the transverse acoustic phonon modes, which may correspond to the lifetime and size of cages formed instantaneously in liquid Ga.
A newly designed magnifying endoscope featuring an endocytoscopy function provided by ultrahigh magnification was evaluated in a pilot study in patients with various types of benign and malignant ...pathology in the esophagus.
Seventy-five consecutive patients were included in the study from 15 March to 21 December 2005. Twenty-nine patients with specific esophageal lesions that had been detected by regular or narrow-band imaging, or both, were further evaluated using endocytoscopy, followed by tissue biopsy or resection. During the endocytoscopic examinations, the esophageal mucosa was stained with 0.5 % methylene blue. The endocytoscopic findings were graded from 1 to 5 in an endocytoscopic atypia (ECA) classification. The final histopathological diagnoses based on biopsies or resected specimens were as follows: category 1 in the Vienna classification, n = 4; category 2, n = 6; category 3, n = 1; category 4, n = 10; and category 5, n = 7. The endocytoscopic diagnoses were compared with the histopathological diagnoses.
Clear endocytoscopic images were obtained in all cases. In definitely malignant lesions, the cell nuclei had an enlarged and irregularly arranged appearance (grade ECA 5). The positive predictive value for malignancy (grades ECA 4 and 5) was 94 %; the false-negative rate was 16.7 %, and the false-positive rate was 6.3 %. The overall accuracy of endocytoscopy for differentiating between nonmalignant tissue (categories 1 - 3 in the Vienna classification) and malignant tissue (categories 4 and 5) was 82 %.
These preliminary results suggest that incorporating endocytoscopy facilities into a standard endoscope may be helpful in characterizing tissue in a variety of esophageal lesions. The potential clinical impact of this method in relation to other gastrointestinal organs requires further study.