ABO-Incompatible Living Kidney Transplants: Evolution of Outcomes and Immunosuppressive Management.

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.

Expression of B7-H3, a potential factor of tumor immune evasion in combination with the number of regulatory T cells, affects against recurrence-free survival in breast cancer patients.

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.

Collective excitations in a melt of fast phase change material GeCu2Te3.

Inelastic x-ray scattering measurements have been carried out to investigate atomic dynamics in a melt of fast phase change material GeCu2Te3. The dynamic structure factor was analysed using the model function with three damped harmonic oscillator components. By investigating the correlation between the excitation energy and the linewidth, and that between the excitation energy and the intensity on contour maps of a relative approximate probability distribution function proportional toexp(-χ2/N), we could judge the reliability of each inelastic excitation in the dynamic structure factor. The results indicate that there are two inelastic excitation modes besides the longitudinal acoustic one in the liquid. The lower energy excitation could be assigned to the transverse acoustic one whereas the higher energy one disperses like fast sound. The latter result may imply that the liquid ternary alloy exhibits a microscopic phase separation tendency.

Structural origins of the unusual thermal stability of amorphous CuxGe50-xTe50(0⩽x⩽33.3).

We have investigated the local atomic structures of several compositions of the amorphous phase of the system CuxGe50-xTe50(0⩽x⩽33.3), based on extended x-ray absorption fine-structure as well as anomalous x-ray scattering experiments, and discuss the unusual trend regarding their thermal stability as a function of the Cu content. At low concentrations (x⩽15), Cu atoms tend to agglomerate in flat nanoclusters reminiscent of the crystalline phase of metallic Cu, leading to a more and more Ge-deficient Ge-Te host network structure with growing Cu content and an increasing thermal stability. At higher Cu concentrations (x⩾25), Cu is incorporated into the network, leading to an overall weaker bonding situation which is associated with a decreasing thermal stability.

Low energy excitation in liquid Sb and liquid Bi observed in inelastic x-ray scattering spectra.

The dynamic structure factorS(Q,E), whereQandEare momentum and energy transfer, respectively, has been measured for liquid Sb, using inelastic x-ray scattering. A modified damped harmonic oscillator model function was applied to analyseS(Q,E) of liquid Sb and also to that of liquid Bi by Inuiet al(2015Phys. Rev.B92, 054206). The obtained excitation energy was in fairly good agreement with that predicted byab initiomolecular dynamics simulations on these liquid semi-metals. The excitation energy of the longitudinal acoustic mode in liquid Sb and liquid Bi exhibits flat-toppedQdependence whereas the lower excitation energy below the longitudinal acoustic excitation showsQ-gap behaviour. From the viscosity estimated from theQ-gap experimentally obtained, it is inferred that the lower energy excitation arises from the transverse acoustic excitation in the liquids.

Isolation, evaluation and use of two strong, carbon source-inducible promoters from Corynebacterium glutamicum.

AIMS: To obtain strong, carbon source-inducible promoters useful for industrial applications of Corynebacterium glutamicum. METHODS AND RESULTS: DNA microarray and qRT-PCR enabled identification of the promoters of cgR_2367 (malE1) and cgR_2459 (git1) as strong, maltose- and gluconate-inducible promoters, respectively, in C. glutamicum. Promoter probe assays revealed that in the presence of the inducing sugars, PmalE1 and Pgit1, respectively, facilitated 3.4- and 4.2-fold increased beta-galactosidase activities compared to the same activity induced by glucose. In addition, PmalE1 was not functional in Escherichia coli, in which Pgit1 function was repressible, which enabled the cloning of a hitherto 'difficult-to-clone' heterologous gene of a lignocellulolytic enzyme, whose secretion was consequently induced by the carbon sources. CONCLUSIONS: PmalE1 and Pgit1 are strong, carbon source-inducible promoters of C. glutamicum whose characteristics in E. coli are integral to the secretion ability of C. glutamicum to secrete lignocellulolytic enzyme. SIGNIFICANCE AND IMPACT OF THE STUDY: Corynebacterium glutamicum, like its counterpart industrial workhorses E. coli and Bacillus subtilis, does exhibit strong, carbon source-inducible promoters, and the functionality of two of which was demonstrated in this study. While this study may be most relevant in the ongoing efforts to establish technologies of the biorefinery, it should also be of interest to general microbiologists exploring the versatility of industrial micro-organisms. In so doing, the study should impact future advances in industrial microbiology.

Experimental observation of density fluctuations in liquid metals associated with liquid-liquid, liquid-gas and metal-nonmetal transitions.

We have developed a special technique and succeeded to carry out small-angle x-ray scattering measurements for some liquid metal systems. The purpose is to investigate effects of transitions such as liquid-liquid (LLT), liquid-gas (LGT) and metal-nonmetal (MNMT) transitions on mesoscopic density fluctuations in liquids. In liquid Te systems (Se-Te and Ge-Te mixtures), which show continuous LLT accompanying MNMT, parameters of density fluctuations show maxima almost in the middle of the transition, both in strength and spatial size. This work (and Kajihara et al 2012 Phys. Rev. B86 214202) was the first direct observation that density fluctuations exhibit maximum corresponding to LLT. However in this study, we could not clearly separate the effects of LLT and MNMT on the observed density fluctuations. Thus, we also investigated fluid Hg under high pressure and high temperature conditions, which shows MNMT near a critical point of LGT, to investigate how MNMT affects them. We observed distinct density fluctuations; a strength and a correlation length of them show maxima at around a critical isochore of LGT, and the former is basically consistent with a phase diagram (compressibility) of LGT; they do not show any peaks at MNMT region. Precise analysis revealed that MNMT only affects a shift of another parameter, a short-range correlation length. These results in fluid Hg indicate that the density fluctuations are mainly derived from a critical phenomena of LGT and MNMT does not play any critical role on them. We believe that the latter conclusion also holds true for liquid Te systems; MNMT plays no important role on the density fluctuations in liquid Te systems and LLT is the main origin of them.

Peculiar temperature dependence of dynamical sound speed in liquid Se50Te50 by inelastic x-ray scattering.

Inelastic x-ray scattering (IXS) measurements were carried out on liquid Se50Te50 at temperatures up to 1323 K to investigate how the atomic dynamics changes with temperature through the semiconductor-metal transition. The acoustic mode was clearly observed in the dynamic structure factor and its energy was determined using a damped harmonic oscillator model. The dynamical sound speed obtained by IXS for [Formula: see text] nm-1 was found to behave similarly to the temperature dependence of ultrasonic sound velocity with a minimum near the semiconductor metal transition. The results can be explained by taking liquid Se50Te50 to be an inhomogeneous liquid consisting of metallic and semiconducting domains whose size is approximately 3 nm. The relaxation time obtained from frequency dependence of the dynamical sound speed was on a picosecond time scale.

Ultrastructure of the calcium release channel of sarcoplasmic reticulum.

This study is concerned with the characterization of the morphology of the calcium release channel of sarcoplasmic reticulum (SR) from fast-twitch skeletal muscle, which is involved in excitation-contraction coupling. We have previously purified the ryanodine receptor and found it to be equivalent to the feet structures, which are involved, in situ, in the junctional association of transverse tubules with terminal cisternae of SR. The receptor is an oligomer of a single high molecular weight polypeptide and when incorporated into phospholipid bilayers, has channel conductance which is characteristic of calcium release in terminal cisternae of SR. The purified channel can be observed by electron microscopy using different methods of sample preparation, with complementary views being observed by negative staining, double staining, thin section and rotary shadowing electron microscopy. Three views can be observed and interpreted: (a) a square face which, in situ, is junctionally associated with the transverse tubule or junctional face membrane; (b) a rectangle equivalent to the side view; and (c) a diamond shape equivalent to the side view, of which the base portion appears to be equivalent to the transmembrane segment. Negative staining reveals detailed substructure of the channel. A computer averaged view of the receptor displays fourfold symmetry and ultrastructural detail. The dense central mass is divided into four domains with a 2-nm hole in the center, and is enclosed within an outer frame which has a pinwheel appearance. Double staining shows substructure of the square face in the form of parallel linear arrays (six/face). The features of the isolated receptor can be correlated with the structure observed in terminal cisternae vesicles. Sections tangential to the junctional face membrane reveal that the feet structures (23-nm squares) overlap so as to enclose smaller square spaces of approximately 14 nm/side. We suggest that this is equivalent to the transverse tubule face and that the terminal cisternae face is smaller (approximately 17 nm/face) and has larger alternating spaces as a consequence of the tapered sides of the foot structures. Image reconstruction analysis appears to be feasible and should provide the three-dimensional structure of the channel.

High frequency dynamics in liquid nickel: An inelastic x-ray scattering study.

Owing to their large relatively thermal conductivity, peculiar, nonhydrodynamic features are expected to characterize the acousticlike excitations observed in liquid metals. We report here an experimental study of collective modes in molten nickel, a case of exceptional geophysical interest for its relevance in earth interior science. Our result shed light on previously reported contrasting evidences: In the explored energy-momentum region, no deviation from the generalized hydrodynamic picture describing nonconductive fluids is observed. Implications for high frequency transport properties in metallic fluids are discussed.

Structural and electronic properties of expanding fluid metals.

It has been theoretically predicted that interacting electron gas suffers a negative compressibility when the electron density is sufficiently reduced. Dielectric anomaly is another expression of compressional instability in which the static dielectric function of electron gas changes sign from positive to negative. In a medium with a negative dielectric function, like charges can attract. Expanding fluid alkali metals are the ideal system in which such instability of electron gas can be probed via the structural response of ions. We have performed x-ray diffraction and small angle x-ray scattering measurements using synchrotron radiation for expanding fluid rubidium and cesium. On the basis of the experimental results we discuss the existence of compressional instability and dielectric anomaly in three-dimensional electron gas.

Mechanisms of inhibitory effects of CoQ10 on UVB-induced wrinkle formation in vitro and in vivo.

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.

Living Related Renal Transplantation Using a Saphenous Vein Graft: A Case Report.

We report a case of living related renal transplantation that used the recipient's saphenous vein as a graft to extend the length of the right donor renal vein. A 41-year-old woman underwent ABO-incompatible living related renal transplantation from her 74-year-old mother in November 2014. A retroperitoneal laparoscopic right donor nephrectomy was performed, because the right kidney showed a cyst on preoperative computed tomography. As the right kidney after donor nephrectomy had a short renal vein and the kidney was large at 280 g, anastomosis with the external iliac vein was difficult. Therefore, we obtained the recipient's 15-cm-long right saphenous vein and created a 1 cm saphenous vein graft. We anastomosed 1 side of the saphenous vein graft to the allograft renal vein in bench surgery and performed end-to-side anastomosis of the other end to the recipient's external iliac vein. The allograft renal artery was used to perform end-to-end anastomosis to the recipient's internal iliac artery. Allograft kidney function was good after transplantation. When the longer axis of the renal graft vein is short, as in the right kidney, a saphenous vein graft may be useful.

Static and dynamic structures of liquid Ba8Ga16Sn30: a melt of the thermoelectric clathrate compounds.

X-ray diffraction and inelastic x-ray scattering measurements of liquid Ba8Ga16Sn30 have been carried out to investigate local structure and atomic dynamics in the liquid. The pair distribution function shows shorter and longer interatomic distances in the first coordination shell. The dynamic structure factor exhibits the inelastic excitations on both sides of the quasielastic central peak. The inelastic excitations disperse with increasing the momentum transfer, suggesting the longitudinal acoustic mode. We found a low energy excitation in addition to the longitudinal acoustic excitation in the dynamic structure factor and it reminds us a strong relationship with a rattling motion of a guest (Ba) atom in the solid state. The temperature dependence of the pair distribution function and the longitudinal acoustic excitation energy is very weak in a range from 600 to 900 °C. The result suggests that Ba and other atoms in the melt are located around minimum positions of the effective pair potential approximated as a harmonic one.

Follow-up Survey of Donor Candidates for Living Related Kidney Transplantation With Prostate Cancer.

INTRODUCTION: With the increasing number of elderly kidney donor candidates due to the lack of available donors, prostate cancer has sometimes been detected in these candidates during pretransplant screening examinations. There are currently no guidelines or consensus on prostate cancer screening and treatment in donors. We retrospectively evaluated the clinical course of donor candidates with prostate cancer. METHODS: Between January 2006 and December 2016, 9 donor candidates for living related kidney transplantation were incidentally diagnosed with prostate cancer at our institution. All male kidney transplant donor candidates routinely received prostate-specific antigen (PSA) testing. The patients with PSA levels > 4.0 ng/mL underwent prostate biopsies. For future kidney transplantation, treatment for localized prostate cancer was prostatectomy. RESULTS: Seven low- or intermediate-risk patients according to the D'Amico risk classification underwent endoscopic prostatectomy, while 2 high-risk patients underwent high dose-rate brachytherapy to prioritize prostate cancer treatment. Of the 7 who underwent surgery, 3 patients ultimately became living related kidney transplantation donors for their wives. There was no recurrence of PSA elevation after treatment. CONCLUSION: This study showed that donor candidates with prostate cancer could safely donate a kidney after a thorough evaluation to exclude those with high-risk prostate cancer. Transmission of prostate cancer through kidney transplantation seems unlikely and robot-assisted laparoscopic prostatectomy may be feasible for donor candidates with localized prostate cancer.

Viscoelastic anomaly accompanying anti-crossing behaviour in liquid As2Se3.

We investigate the dynamic structure factor of the melt of the well known glass former, As2Se3, using inelastic x-ray scattering for temperatures, T, [Formula: see text] K and momentum transfers Q from [Formula: see text] nm-1. An anomaly was observed at Q = 2.7 nm-1 ([Formula: see text] K) with, in the context of a simple model, both an abrupt change in frequency and an increased linewidth reminiscent of an anti-crossing in a solid. Comparison with structural information from reverse Monte Carlo modeling of x-ray diffraction data allows us to associate the disappearance of the anomaly at higher temperatures with a drop in the number of mechanical constraints per atom, n mc, to [Formula: see text] reminiscent of the threshold applicable for glass formation in rigidity theory. It is inferred that the surprising jump in the dispersion in the liquid may be correlated with a stiffness transition in a network glass.

Divergent mechanisms of 5' 23S rRNA IVS processing in the alpha-proteobacteria.

Widespread occurrence of a separate small RNA derived from the 5'-end of 23S rRNA and of an intervening sequence (IVS) which separates this domain from the main segment of 23S rRNA in the alpha-proteobacteria implies that processing reactions which act to excise the IVS are also maintained in this group. We previously characterized the first example of processing of this IVS in Rhodopseudomonas palustris, which is classified with the Bradyrhizobia In this case, IVS excision occurs by a multistep process and RNase III appears to act at an early step. Here, we characterize in vivo and in vitro IVS processing in two other related, but phenotypically distinct, Bradyrhizobia We also examine in vivo and in vitro processing of rRNA precursors from a more distantly related alpha-proteobacterium, Rhodobacter sphaeroides which produces a separate 5' 23S rRNA domain but has different sequences in the 5' 23S rRNA IVS. The details of the in vivo processing of all of the Bradyrhizobial rRNAs closely resemble the R. palustris example and in vitro studies suggest that all of the Bradyrhizobia utilize RNase III in the first step of IVS cleavage. Remarkably, in vivo and in vitro studies with R.sphaeroides indicate that initial IVS cleavage uses a different mechanism. While the mechanism of IVS cleavage differs among these alpha-proteobacteria, in all of these cases the limits of the internal segments processed in vivo are almost identical and occur far beyond the initial cleavage sites within the IVSs. We propose that these bacteria possess common secondary maturation pathways which enable them to generate similarly processed 23S rRNA 5'- and 3'-ends.

Characterization of a separate small domain derived from the 5' end of 23S rRNA of an alpha-proteobacterium.

We demonstrate the presence of a separate processed domain derived from the 5' end of 23S rRNA in ribosomes of Rhodopseudomonas palustris, a member of the alpha-++proteobacteria. Previous sequencing studies predicted intervening sequences (IVS) at homologous positions within the 23S rRNA genes of several alpha-proteobacteria, including R.palustris, and we find a processed 23S rRNA 5' domain in unfractionated RNA from several species. 5.8S rRNA from eukaryotic cytoplasmic large subunit ribosomes and the bacterial processed 23S rRNA 5' domain share homology, possess similar structures and are both derived by processing of large precursors. However, the internal transcribed spacer regions or IVSs separating them from the main large subunit rRNAs are evolutionarily unrelated. Consistent with the difference in sequence, we find that the site and mechanism of IVS processing also differs. Rhodopseudomonas palustris IVS-containing RNA precursors are cleaved in vitro by Escherichia coli RNase III or a similar activity present in R.palustris extracts at a processing site distinct from that found in eukaryotic systems and this results in only partial processing of the IVS. Surprisingly, in a reaction unlike characterized cases of eubacterial IVS processing, an RNA segment larger than the corresponding DNA insertion is removed which contains conserved sequences. These sequences, by analogy, serve to link the 23S rRNA 5' rRNA domains or 5.8S rRNAs to the main portion of other prokaryotic 23S rRNAs or to eukaryotic 28S rRNAs, respectively.

Robot-Assisted Radical Prostatectomy for Localized Prostate Cancer in Asian Renal Transplant Recipients.

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.

Cloning of dnaK and dnaJ homologous genes from a purple non-sulfur bacterium Rhodopseudomonas species.

The dnaK and dnaJ genes were isolated as a cluster from a purple non-sulfur phototrophic bacterium, Rhodopseudomonas species No. 7 by a polymerase chain reaction (PCR) based method. The deduced products of dnaK (631 amino acids) and dnaJ (379 amino acids) were 67% and 56% identical to the respective Escherichia coli gene products. The functions of DnaK and DnaJ could be confirmed by complementation of the respective E. coli mutants.