An artificial impact on the asteroid (162173) Ryugu formed a crater in the gravity-dominated regime.

The Hayabusa2 spacecraft investigated the small asteroid Ryugu, which has a rubble-pile structure. We describe an impact experiment on Ryugu using Hayabusa2's Small Carry-on Impactor. The impact produced an artificial crater with a diameter >10 meters, which has a semicircular shape, an elevated rim, and a central pit. Images of the impact and resulting ejecta were recorded by the Deployable CAMera 3 for >8 minutes, showing the growth of an ejecta curtain (the outer edge of the ejecta) and deposition of ejecta onto the surface. The ejecta curtain was asymmetric and heterogeneous and it never fully detached from the surface. The crater formed in the gravity-dominated regime; in other words, crater growth was limited by gravity not surface strength. We discuss implications for Ryugu's surface age.

IMPACT ON ABSORBED DOSE RATE IN AIR IN KANTO REGION BY FUKUSHIMA DAIICHI NUCLEAR POWER PLANT ACCIDENT.

Absorbed dose rates in air were measured for the whole area of the Kanto region in 2015, 2016 and 2017 (n = 31 147). The mean absorbed dose rates in air for each prefecture measured by car-borne surveys were from 44 to 67 nGy h-1 (13-289 nGy h-1). The absorbed dose rate in air from artificial radionuclides (134Cs + 137Cs) measured by fixed-point observation (n = 507) was from 1 to 14 nGy h-1 (0-105 nGy h-1), and meaning that the contribution ratios of 134Cs and 137Cs were 3-22%. The deposited location of artificial radionuclides was less than 1000 m from ground level and depended on the topography, wind direction and precipitation field.

Severe Phlebitis Accompanying Vascular Rejection Type Acute T Cell-Mediated Rejection in Renal Transplantation.

PURPOSE: Renal transplant patients with vascular rejection type acute T cell-mediated rejection (ATCMR) grade II have a poor prognosis. Vascular lesions in those cases are thought to randomly occur, thus we searched for a novel pathological marker related to vascular rejection in kidney transplantation. METHODS: We determined pathological characteristics in 14 ATCMR grade II patients treated during an acute phase from 2004 to 2013. We then examined whether those findings appeared in transplant kidney biopsy specimens, except for cases of vascular rejection, in patients examined from 2010 to 2014. RESULTS: In 9 of the 14 ATCMR grade II patients, phlebitis was accompanied by inflammatory cells that formed polypoid projections in the venous lumen and partial disappearance of vascular endothelium. Further investigation showed those inflammatory cells to be T cells and macrophages. Histological findings revealed coexisting phlebitis in 2 of 13 patients with ATCMR grade I, 3 of 24 with borderline changes, and none with normal findings. Phlebitis occurred at a significantly greater rate than the other findings in cases of vascular rejection (P < .05). However, there was no significant difference in regard to graft survival between patients with and without phlebitis (P = .1829). CONCLUSION: Our results suggest severe phlebitis as a novel finding associated with the pathology of vascular rejection in patients with a renal allograft.

Comparison of Sensitivity of Immunocomplex Capture Fluorescence Analysis for Detecting Donor-specific Anti-HLA Class II Antibodies in Kidney Transplant Patients.

BACKGROUND: Immunocomplex capture fluorescence analysis (ICFA) detects donor-specific antihuman leukocyte antigen (HLA) antibodies (DSA), but the detection sensitivity of HLA class II antibodies using conventional ICFA is as low as 57%. The aim of the study was to improve the detection sensitivity of HLA class II antibodies by ICFA, and compare the ICFA results with the Luminex single-antigen bead test. METHODS: Six DSA-negative kidney transplant donors and recipient pairs and 10 HLA class II DSA-positive pairs were included in the study. The detection sensitivity of modified ICFA was compared with conventional ICFA, and the ICFA results were compared with the Luminex single-antigen bead test. RESULTS: The index value of modified ICFA was higher than that of conventional ICFA. The cutoff value of conventional ICFA was 30,686 (MFI), which was improved to 19,405 using modified ICFA. Regarding the HLA-DQ antibody, 5 samples found to be positive by Luminex single-antigen bead testing were all negative using modified ICFA. The reason for this discrepancy could be related to: (1) the difference in detection sensitivity; (2) the difference in HLA antigen surface expression between naive lymphocytes and synthetic beads; or (3) the structure of synthetic HLA DQ antigen on the Luminex single-antigen beads. CONCLUSION: The index value of the modified ICFA was higher than that of conventional ICFA, and the detection sensitivity of HLA class II antibodies was improved by modified ICFA. Further assessment is necessary to clarify the reasons for divergence between ICFA and Luminex single-antigen bead test results.

Properties of the feline tumour suppressor reduced expression in immortalized cells (REIC/Dkk-3).

Reduced expression in immortalized cells (REIC/Dkk-3), a member of the human Dickkopf (Dkk) family, is a growth suppressor in human and canine mammary tumours. Mammary gland tumours are common neoplasms with high malignancy in female cats. The purpose of this study was to clone the feline REIC/Dkk-3 homolog, investigate its expression in cell lines established from feline mammary gland tumours, and test its tumour suppressor function. Western blot analysis revealed that expression of the REIC/Dkk-3 protein was reduced in feline mammary carcinoma cell lines. Forced expression of REIC/Dkk-3 induced apoptosis in feline mammary tumour cell lines. These results demonstrate that REIC/Dkk-3 expression, which is downregulated in feline mammary tumour cell lines, results in the induction of apoptosis in these cells. Our findings suggest that feline REIC/Dkk-3 represents a potential molecular target for the development of therapies against feline mammary cancers.

Plasmodium knowlesi and human malaria parasites in Khan Phu, Vietnam: Gametocyte production in humans and frequent co-infection of mosquitoes.

Four species of malaria parasite, Plasmodium falciparum, Plasmodium vivax, Plasmodium malariae and Plasmodium knowlesi infect humans living in the Khanh Phu commune, Khanh Hoa Province, Vietnam. The latter species also infects wild macaque monkeys in this region. In order to understand the transmission dynamics of the three species, we attempted to detect gametocytes of the three species in the blood of infected individuals, and sporozoites in the salivary glands of mosquitoes from the same region. For the detection of gametocyte-specific mRNA, we targeted region 3 of pfg377, pvs25, pmg and pks25 as indicators of the presence of P. falciparum, P. vivax, P. malariae and P. knowlesi gametocytes, respectively. Gametocyte-specific mRNA was present in 37, 61, 0 and 47% of people infected with P. falciparum (n = 95), P. vivax (n = 69), P. malariae (n = 6) or P. knowlesi (n = 32), respectively. We found that 70% of mosquitoes that had P. knowlesi in their salivary glands also carried human malaria parasites, suggesting that mosquitoes are infected with P. knowlesi from human infections.

Induction Immunosuppressive Therapy With Everolimus and Low-Dose Tacrolimus Extended-Release Preserves Good Renal Function at 1 Year After Kidney Transplantation.

BACKGROUND: Utilization of everolimus (EVR) has been increasing in recent years for patients undergoing renal transplantation to reduce calcineurin inhibitor (CNI) levels. However, an optimum regimen has yet to be established. METHODS: We retrospectively examined 12 renal transplant recipients who underwent an induction immunosuppressive protocol; the protocol comprises 5 agents, including EVR plus low-dose tacrolimus extended-release (TAC-ER) treatment. We compared those findings from those of 14 patients who underwent a conventional protocol without EVR. Clinical outcome and pathologic changes were assessed by using protocol graft biopsy findings obtained at 3 months and 1 year after transplantation. RESULTS: The estimated glomerular filtration rate was significantly higher for the EVR group at both 3 months and 1 year compared with the conventional group (P < .01 and P = .03, respectively). TAC-ER trough levels were also significantly lower at 3 months and 1 year (both, P < .01). Histologic findings of the 3-month protocol biopsy samples in the EVR group revealed 4 cases of borderline change and 2 of acute cellular-mediated rejection. The findings from the 1-year biopsy samples revealed 10 cases with normal findings with no evidence of CNI toxicity. Patients in the EVR group developed subclinical borderline change and acute cellular-mediated rejection after 3 months at a significantly higher rate than the conventional group (P = .02). CONCLUSIONS: Use of the present therapeutic strategy successfully maintained the trough of each drug at a lower level, and it also kept renal function stable up to 1 year after transplantation.

Post-Transplant Anemia Has Strong Influences on Renal and Patient Outcomes in Living Kidney Transplant Patients.

BACKGROUND: Post-transplant anemia (PTA) is a risk factor for mortality and graft loss in kidney transplant patients. METHODS: In all, 172 patients were included in this study. PTA was defined as hemoglobin <13.0 g/dL in men and 12.0 g/dL in women. The primary outcome of interest was the renal outcome, defined as a 50% increase in serum levels of creatinine, a return to chronic dialysis, and subsequent kidney transplantation (KTx). The secondary outcome was a composite of the primary outcome and death. RESULTS: At baseline, 75 patients (43.6%) had PTA. During follow-up of a median of 7.3 years, 52 patients (30.2%) had 2-fold higher creatinine levels than at baseline, 24 patients (14.0%) had to return to chronic dialysis or subsequent KTx, and 11 patients (6.4%) died; 8 (4.7%) of the deceased patients had functioning allografts. Univariate regression analyses showed that a lower hemoglobin level and positive proteinuria were significantly associated with both outcomes. After adjusting for important clinical variables, a lower hemoglobin level remained a strong predictor for both outcomes. Restricted cubic splines showed an almost linear inverse association with a hemoglobin level ≥12 g/dL. The risk of the outcomes increased with decreasing tertiles of the baseline hemoglobin level for both men and women, but the associations in women were much weaker than those in men, suggesting a different prognostic value of the hemoglobin level between men and women. CONCLUSIONS: PTA strongly influenced the renal and patient outcomes in living kidney transplant patients.

Adherence to Dietary Recommendations in Maintenance Phase Kidney Transplant Patients.

OBJECTIVES: Current adherence to dietary recommendations for chronic kidney disease was evaluated in kidney transplant patients in the maintenance phase. METHODS: A total of 268 maintenance phase kidney transplant patients were included in the study. Estimated daily intakes of oral protein and salt were calculated from 24-h urinary excretion of nitrogen and sodium, respectively. Dietary recommendations for chronic kidney disease, as issued in 2014 by the Japanese Society of Nephrology, were used as the basis for assessing diet. RESULTS: The study included 114 female patients and 154 male patients. The mean age, posttransplantation years, body mass index, estimated glomerular filtration rate, and 24-h urinary excretion of protein were 56.3 years, 11.2 years, 22.0 kg/m(2), 42.6 mL/min/1.73 m(2), and 321 mg/d, respectively. Estimated daily protein and salt intakes were 0.98 ± 0.26 g/kg/d and 9.3 ± 3.9 g/d. Only 47 patients (17.5%) in the case of salt intake and 105 patients (39.2%) in the case of protein intake were within reference values. The 24-h urinary protein excretion of the daily salt intake-adherent group (<6 g) was significantly less than that of the nonadherent group (≥6 g) (P = .021). CONCLUSIONS: The adherence rate to dietary recommendations for chronic kidney disease in kidney transplant patients was low. The 24-h urinary protein excretion of the daily salt intake-adherent group was significantly less than that of the nonadherent group. Dietary therapy for these patients may have the potential to improve kidney graft function and survival.

Early microchimerism in peripheral blood following kidney transplantation.

BACKGROUND: The role of microchimerism found in the peripheral blood of renal transplant recipients remains a matter of debate. We assessed the frequency of microchimerism after kidney transplantation and examined its influence on clinical courses over a 12-month follow-up period. PATIENTS AND METHODS: Ten single-kidney recipients underwent microchimerism detection at 2 days, 2 weeks, and 1, 3, 6, and 12 months after transplantation, with mismatch human leukocyte antigen (HLA)-A, -B, and -C used as markers. RESULTS: Microchimerism was detected in 8 (80%) patients at 2 days after kidney transplantation. In 3 of those, microchimerism became negative within 3 months after transplantation, whereas it remained present for up to 12 months in 3 patients (33 %). There was 1 acute rejection episode in a patient in whom microchimerism became negative within 3 months. Protocol renal graft biopsy specimens obtained 3 months after transplantation revealed no acute cellular-mediated rejection (ACMR) or acute antibody-mediated rejection (AAMR) in the 5 patients positive for microchimerism at 3 months. CONCLUSIONS: Microchimerism was frequently detected after kidney transplantation. Microchimerism that remained for more than 3 months post-transplantation might be correlated with a lower incidence of rejection, thus its monitoring may help identify recipients with a low rejection risk.

Conversion to mycophenolate mofetil from azathioprine shows significant positive effect on graft function in long-term past-kidney transplantation stable-state patients.

OBJECTIVES: A number of reports have shown that the efficacy of mycophenolate mofetil (MMF) is superior to that of azathioprine (AZP) for long-term kidney allograft survival. We conducted a retrospective single-center study to evaluate renal function more than 2 years after conversion from AZP to MMF in kidney transplant recipients several years after transplantation. METHODS: AZP was converted to MMF in 51 recipients at 17.0 ± 0.8 years after kidney transplantation who were followed up for more than 2 years after conversion. Estimated glomerular filtration rate (eGFR) was determined using the Formula of the Japanese Society of Nephrology. RESULTS: The eGFR was significantly greater at 1 year before conversion (41.72 ± 1.91 mL/min/1.73 m(2)) as compared with the day of conversion (39.04 ± 1.82 mL/min/1.73 m(2); P < .05). After conversion, eGFR plateaued to 39.30 ± 2.01 mL/min/1.73 m(2) at 1 year and 38.24 ± 2.42 mL/min/1.73 m(2) at 2 years after conversion. The average eGFR slopes were -2.96 ± 0.36 mL/min/1.73 m(2) per year for AZP and 1.22 ± 0.10 mL/min/1.73 m(2) per year for MMF (P < .0001). Cyclosporine (CSA) was reduced from 176 ± 9.3 to 165 ± 9.8 mg/d (P = .0394) after the switch, whereas the CSA trough level was increased from 77.3 ± 6.6 to 118 ± 9.8 ng/mL (P = .0017). Furthermore, the daily dose of tacrolimus (TAC) was decreased from 3.5 ± 0.3 to 3.1 ± 0.3 mg/d (P = .0083). CONCLUSIONS: Our findings demonstrated the safety of conversion from AZP to MMF even in the patients who underwent renal transplantation several years prior. In addition, these short-term results indicated the improvement in allograft function following conversion.

Excellent results of immunocomplex capture fluorescence analysis-I for cross-match test in renal transplantation.

A flow cytometry cross-match (FCXM) test is the gold standard for detection of human leukocyte antigen (HLA) antibodies in renal transplantation because of its high sensitivity. However, this technique can produce false-positive results when non-HLA antibodies or low-titer donor-specific antibodies (DSA) are detected. To determine the clinical relevance of the recently introduced novel cross-match test termed immunocomplex capture fluorescence analysis (ICFA), we retrospectively compared the results of ICFA and FCXM, including a single-antigen bead test for detection of DSA in renal transplant recipients. We found a correlation of 71.4% (235/329) between the results of ICFA-I and FCXM-T, whereas that between ICFA-II and FCXM-B was 41.1% (134/326). Ninety-four patients were ICFA-I negative and FCXM-T positive, and 188 were ICFA-II negative and FCXM-B positive, whereas 46.8% (44/94) and 61.7% (116/188) were found to be DSA-I and DSA-II negative, respectively, which classified them into the non-HLA antibody and low-titer DSA groups, respectively. The mean value of molecules of equivalent soluble fluorochrome for DSA-I was 22,994 in the ICFA-I-positive group, which was significantly higher than 2117 in the negative group (P < .0001), whereas there was no significant difference for DSA-II between the ICFA-II-positive and ICFA-II-negative groups. Graft survival in the ICFA-I-negative group was significantly higher than that in the ICFA-I-positive group (P = .0058). Our results indicate that ICFA-I does not respond to non-HLA antibodies or low-titer DSA, which have influence on graft survival. Therefore, this novel hybrid test, which combines cross-match testing and HLA antibody detection functions, may be useful for clinical pretransplantation evaluation of renal transplantation patients.

Clinical and virologic courses of hepatitis B surface antigen-negative and hepatitis B core or hepatitis B surface antibody-positive renal transplant recipients.

Recent findings suggest that reactivation of hepatitis B (HB) virus (HBV) in renal transplantation recipients with a past HBV infection is an important cause of morbidity and mortality. In the present study, we reviewed the clinical and virologic courses of past HBV infections in recipients following renal transplantation. We retrospectively analyzed pretransplant HB surface antigen (HBsAg), HB core antibody (HBcAb), HB surface antibody (HBsAb), and HBV deoxyribonucleic acid (DNA) levels in 147 patients who underwent renal transplantation at our institution between September 2000 and November 2011. Thirty-four (23.1%) of the patients were diagnosed with a past HBV infection. The mean age of patients with a past HBV infection was significantly older than that of those without (48.4 vs 41.1 years, P = .002), while the duration of hemodialysis (HD) was significantly longer (138 vs 79.5 months, P = .027) and ratio of cadaveric transplantation procedures was higher (41.2% vs 21.2%, P = .035). During the follow-up period after renal transplantation, HBsAg was negative, HBV DNA was undetectable, and serum alanine aminotransferase level was normal in all patients. There were no statistically differences for graft and patient survival, and serum creatinine level between patients with and without a past HBV infection. Our results indicate that a past HBV infection is significantly associated with older age, longer duration of HD, and cadaveric transplantation. However, no HBV reactivation occurred in our previously infected patients, and the presence of HBcAb or HBsAb positivity did not influence graft or patient survival or renal function following renal transplantation.

Serum adiponectin and leptin levels are useful markers for prostate cancer screening after adjustments for age, obesity-related factors, and prostate volume.

AIM: Adiponectin and leptin, polypeptide hormones produced by adipocytes, have recently been reported to be associated with prostate cancer risk, though, the relationship remains poorly understood. We examined the association of adiponectin and leptin levels in serum with prostate cancer risk after adjustments for age, obesity-related factors, and prostate cancer risk. METHODS: Fifty-four prostate cancer patients and 70 control subjects provided blood sampled between 2008 and 2009. Using those, we determined serum adiponectin and leptin levels, and evaluated their relationships with prostate cancer risk after adjustments for age, obesity-related factors (body weight, body mass index, waist circumference), and prostate volume. Adipokine densities were calculated by dividing serum level with prostate volume. RESULTS: There were no differences for median serum adiponectin and leptin levels between the prostate cancer and benign control groups (P=0.22 and 0.78, respectively). Patients with levels of both adipokines in the highest quartile after adjustment for age had significantly higher risks of prostate cancer (adiponectin: odds ratio [OR] 2.79, P=0.014; leptin: OR 2.72, P=0.027). Patients with an adiponectin level greater than the median after adjustment for body weight also had a significantly elevated risk of prostate cancer (OR 2.22, P=0.031), whereas, those with a leptin level significantly greater than the median had a significantly lower risk (OR 0.46, P=0.027). Furthermore, median adiponectin density was significantly higher in the prostate cancer group than the benign group (P=0.0033). CONCLUSION: Serum adiponectin and leptin levels are useful markers for prostate cancer risk after adjustments for age, obesity-related factors, and prostate volume.

Oncogenic fusion E2A-HLF sensitizes t(17;19)-positive acute lymphoblastic leukemia to TRAIL-mediated apoptosis by upregulating the expression of death receptors.

t(17;19)-acute lymphoblastic leukemia (ALL) shows extremely poor prognosis. E2A-HLF derived from t(17;19) blocks apoptosis induced by the intrinsic mitochondrial pathway and has a central role in leukemogenesis and chemoresistance. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is expressed on cytotoxic T cells and natural killer cells and binds with death receptors (DR4/DR5), inducing apoptosis by dual activation of intrinsic and extrinsic pathways, and TRAIL mediates the graft-versus-leukemia (GVL) effect after allogeneic stem cell transplantation (allo-SCT). We found that cell lines and patients' samples of t(17;19)-ALL expressed death receptors for TRAIL, and recombinant soluble TRAIL immediately induced apoptosis into t(17;19)-ALL cell lines. E2A-HLF induced gene expression of DR4/DR5, which was dependent on the DNA-binding and transactivation activities of E2A-HLF through the 5' upstream region of the start site at least in the DR4 gene. Introduction of E2A-HLF into non-t(17;19)-ALL cell line upregulated DR4 and DR5 expression, and sensitized to proapoptotic activity of recombinant soluble TRAIL. Finally, a newly diagnosed t(17;19)-ALL patient underwent allo-SCT immediately after induction of first complete remission, and the patient has survived without relapse for over 3-1/2 years after allo-SCT. These findings suggest that E2A-HLF sensitizes t(17;19)-ALL to the GVL effect by upregulating death receptors for TRAIL.

Nocturnal blood glucose and IGFBP-1 changes in type 1 diabetes: Differences in the dawn phenomenon between insulin regimens.

OBJECTIVE: Insulin-like growth factor binding protein-1 (IGFBP-1) is known to regulate the bioavailability of insulin-like growth factor (IGF) and the levels of IGFBP-1 are increased in the morning in patients with type 1 diabetes mellitus. We investigated the nocturnal fluctuations of glucose, IGFBP-1, and free IGF-1 levels with three insulin regimens. RESEARCH DESIGN AND METHODS: Forty-eight type 1 diabetes patients were divided into three groups according to their basal insulin therapy (continuous subcutaneous insulin infusion [CSII], insulin glargine, NPH insulin). Blood samples were obtained every 2 h between 2 300 h and 0700 h to measure plasma glucose, IGFBP-1 and free IGF-1 levels. RESULTS: The dawn phenomenon was more frequent with NPH (62.1%) than with glargine (16.6%, p<0.05) and CSII (14.3%, p<0.05). In the NPH group, the serum IGFBP-1 levels were markedly increased from 21.0+/-3.6 ng/ml at 2 300 h to 200.3+/-21.8 ng/ml at 0700 h and free IGF-1 levels were inversely decreased; these changes were partially suppressed in the CSII and glargine groups. CONCLUSIONS: The use of insulin regimens that provide sufficient insulin levels in the early morning can suppress the dawn phenomenon, leading to improved glycemic control. The increase in circulating IGFBP-1 in the morning, as a result of waning of insulin action, lowers free IGF-1 levels and may cause insulin resistance.

Little impact of donor/recipient major mismatch for neutrophil-specific antigen NA2 on neutrophil recovery after allogeneic SCT.

The Fcgamma receptor IIIb (FcgammaRIIIb), a receptor for the Fcgamma region of IgG, is specifically expressed on neutrophils. It has two allelic polymorphisms, NA1 and NA2, which are highly immunogenic and act as targets in alloimmune or autoimmune neutropenia. Thus, neutrophil antigens (NA) compatibility of donor/recipient pairs might be expected to affect the engraftment of neutrophils after allogeneic SCT (allo-SCT). Here, the impact of NA compatibility of 17 patients and their donors undergoing allo-SCT with a myeloablative regimen was determined. Leukocyte depletion filters were used for all transfusions before and post-SCT; most patients received G-CSF after transplant. Major mismatches for NA1 and NA2 were present in 1 and 7 patient/donor pairs, respectively. These eight patients receiving NA major-mismatched allo-SCT were compared with nine patients who received NA compatible allo-SCT. Engraftment of neutrophils and the incidence of post-engraftment neutropenia were found to be identical in the two groups. Despite the limitations in statistical power because of the small number of patients analyzed, these observations suggest that the major mismatching for NA2 antigen has little impact on the engraftment of neutrophils after myeloablative allo-SCT, at least in patients transfused using leukocyte depletion filters and receiving G-CSF after transplantation.