bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinicopathological study of de novo membranous nephropathy of ‘stage 0’ after kidney transplantation
Authors: Katsuma Ai , Nakada Yasuyuki , Yamamoto Izumi , Horita Shigeru , Katsumata Haruki , Kobayashi Akimitsu , Unagami Kohei , Okumi Masayoshi , Ishida Hideki , Yokoo Takashi , Yamaguchi Yutaka , Tanabe Kazunari ,   Japan Academic Consortium of Kidney Transplantation (JACK)
Published: July 2018

ABSTRACTAimDe novo membranous nephropathy (dnMN) contributes to graft failure, but the pathophysiology of the disease remains poorly understood. We defined cases exhibiting granular Immunoglobulin G (IgG) immunofluorescence staining but lacking dense deposits on electron microscopy as being of ‘dnMN stage 0’; we studied the associated clinicopathological features.MethodsWe studied 4653 allograft biopsy specimens (from 1747 cases treated in the Department of Urology, Tokyo Women’s Medical University) and found 42 cases of allograft membranous nephropathy, of which 28 (1.6%) were diagnosed as dnMN. Of these, five cases (0.06%) fulfilled the criteria for dnMN stage 0.ResultsAll five cases were diagnosed based on biopsies indicating increased serum levels of creatinine. Proteinuria status varied from negative to 2+. The median period from transplantation to allograft biopsy was 4068 days. Four of the five cases exhibited suspicious antibody‐mediated rejection together with dnMN. The glomerular capillaries of all cases were C4d‐positive, as were the peritubular capillaries of three of the four ABO‐compatible transplants. In terms of IgG subclass, IgG1 and IgG3 predominated in all cases, and phospholipase A2 receptor status (evaluated via immunoreactivity) was negative in all cases. We examined two cases by immunoelectron microscopy using anti‐IgG and anti‐C4d antibodies. We found subendothelial and intramembranous deposits expressing both IgG and C4d, corresponding to positivity in immunofluorescence analysis.ConclusionWe confirmed the existence of dnMN stage 0 by focusing on granular IgG immunofluorescence positivity.
Clinicopathological features and outcomes of kidney allografts in plasma cell‐rich acute rejection: A case series
Authors: Hamada Aki Mafune , Yamamoto Izumi , Kawabe Mayuko , Katsumata Haruki , Yamakawa Takafumi , Katsuma Ai , Nakada Yasuyuki , Kobayashi Akimitsu , Koike Yusuke , Miki Jun , Yamada Hiroki , Kimura Takahiro , Tanno Yudo , Ohkido Ichiro , Tsuboi Nobuo , Yamamoto Hiroyasu , Yokoo Takashi 
Published: July 2018

ABSTRACTPlasma cell‐rich acute rejection (PCAR) is a rare type of acute rejection in renal transplantation. Despite aggressive immunotherapy, approximately 40–60% of patients develop graft loss within 1 year after an episode of PCAR. However, the reason for this outcome remains obscure. This study retrospectively identified six patients with PCAR diagnosed between 2009 and 2015 at a single university hospital. Clinicopathological data were collected. Five of the six patients were male, and mean age at the onset of PCAR was 49.0 ±14.5 years. None of the patients showed overall poor adherence to medication. Mean time to diagnosis was 302 ±234 days post‐transplantation. All patients had preceding or concurrent viral infection. Four patients developed PCAR alone and two patients developed PCAR with antibody‐mediated rejection. One of the six patients showed both severe tubulointerstitial and microvascular inflammation (total of Banff tubulitis ‘t’ + interstitial inflammation ‘i’ + glomerulitis ‘g’ + peritubular capillaritis ‘ptc’ scores >10). This patient had progressive worsening of graft function and re‐initiated dialysis at 74 months after a PCAR episode. In addition, three of the six patients had long‐term recurrence of PCAR. With the recurrence of PCAR, patients with both moderate tubulointerstitial and microvascular inflammation (total of Banff ‘t’ + ‘i’ + ‘g’ + ‘ptc’ scores >6) had progressive worsening of graft function. In summary, the present results suggest that concurrent moderate to severe tubulointerstitial and microvascular inflammation may lead to poor outcomes of graft function after a PCAR episode.
Two novel APOA1 gene mutations in a Japanese renal transplant recipient with recurrent apolipoprotein A‐I related amyloidosis
Authors: Horike Keiji , Takeda Asami , Tsujita Makoto , Goto Norihiko , Watarai Yoshihiko , Uchida Kazuharu , Katayama Akio , Nishihira Morikuni , Shimizu Akira , Nozu Kandai , Morozumi Kunio 
Published: July 2018

ABSTRACTApolipoprotein A‐I amyloidosis is a rare, autosomal dominant disorder of APOA‐1 gene characterized by the deposition of apolipoprotein A‐I in various organs and can be classified into either hereditary or nonhereditary form in the absence of a family history. Renal disease caused by Apolipoprotein A‐I amyloidosis commonly manifested as slowly progressive renal function impairment without heavy proteinuria. Apolipoprotein A‐I‐related amyloidosis of kidney is of pathogenetic interest because the renal failure is due to peritubular and interstitial amyloid deposits without glomerular deposits. Tubulointerstitial lesion of amyloid deposits was diagnosed in half of carriers of APOA1 gene mutation, only 13% of patients progressed to renal failure requiring hemodialysis or kidney transplantation. Recurrence of apolipoprotein A‐I‐related amyloidosis after kidney transplantation is very rare. We report a case of a 63‐year‐old Japanese female without a family history of kidney and/or liver disease who showed slowly progressive renal graft dysfunction without overt proteinuria. Graft biopsy revealed characteristic Congo red stain positive amyloid deposits localized in the renal interstitial area. No glomerular, vascular and tubular amyloid deposits were noted. Laser microdissection‐liquid chromatography tandem mass spectrometry‐based proteomic analysis elucidated the type of amyloidosis as apolipoprotein A‐I amyloidosis. Genetic analysis of DNA sequence study revealed two novel APOA1 gene mutations of Leu202Arg and Lys262Asn. This is a first and very rare case report of the recurrence of non‐familial hereditary apolipoprotein A‐I amyloidosis in Japanese transplant recipient.
Protocol graft biopsy in kidney transplantation
Authors: Sakai Ken , Oguchi Hideyo , Muramatsu Masaki , Shishido Seiichiro 
Published: July 2018

ABSTRACTAccurate interpretation of renal allograft biopsy is necessary to guide therapy, especially when an episode biopsy is taken to rescue the graft. Contrarily, a protocol biopsy is carried out routinely to identify baseline conditions (biopsy at 0 or 1 h), subclinical rejection, histological change under current immunosuppression regimen, drug nephrotoxicity, viral infection, and recurrence of glomerulonephritis. Semiquantitative scoring for active lesions including tubulitis, glomerulitis, capillaritis, arteritis, arteriopathy, and others such as polyomavirus infection are key factors in transplant pathology. Recently, the Banff classification has proposed several novel concepts focused on antibody‐mediated rejection (ABMR). This review presents the interpretation of transplant pathology from rejection to infection, recurrence of glomerulonephritis, and drug nephrotoxicity, with a description of ABMR according to the 2013 and 2017 Banff classification.
Targeting eotaxin‐1 and CCR3 receptor alleviates enteric neuropathy and colonic dysfunction in TNBS‐induced colitis in guinea pigs
Authors: Filippone R. T. , Robinson A. M. , Jovanovska V. , Stavely R. , Apostolopoulos V. , Bornstein J. C. , Nurgali K. 
Published: July 2018

AbstractBackgroundThe accumulation of eosinophils is mediated by the chemokine receptor‐3 (CCR3)‐eotaxin axis. Increased expression of eotaxin and its receptor is associated with inflammatory bowel disease (IBD). Activation of eosinophils causes the release of cationic proteins that are neurotoxic such as eosinophil‐derived neurotoxin (EDN). Damage to enteric neurons alters neurally controlled functions of the gut correlated with intestinal inflammation. We hypothesized that inhibition of the CCR3‐eotaxin axis will prevent inflammation‐induced functional changes to the gastrointestinal tract.MethodsHartley guinea pigs were administered with trinitrobenzene sulfonate (TNBS; 30 mg/kg in 30% ethanol) intrarectally to induce colitis. A CCR3 receptor antagonist (SB 328437 [SB3]) was injected intraperitoneally 1 hour postinduction of colitis. Animals were euthanized 7 days post‐treatment and colon tissues were collected for ex vivo studies. The EDN‐positive eosinophils in the colon, indicating eosinophil activation, were quantified by immunohistochemistry. Effects of SB3 treatment on gross morphological damage, enteric neuropathy, and colonic dysmotility were determined by histology, immunohistochemistry, and organ bath experiments.Key ResultsThe number of EDN‐positive eosinophils was significantly increased in the lamina propria in close proximity to myenteric ganglia in inflamed colon. The TNBS‐induced inflammation caused significant damage to colonic architecture and inhibition of colonic motility. Treatment with SB3 antagonist attenuated inflammation‐associated morphological damage in the colon, reduced infiltration of EDN‐positive eosinophils and restored colonic motility to levels comparable to control and sham‐treated guinea pigs.Conclusion & InferencesThis is the first study demonstrating that inhibition of CCR3‐eotaxin axis alleviates enteric neuropathy and restores functional changes in the gut associated with TNBS‐induced colitis.
Heritability of spotted wilt resistance in a Florida‐EP™ “113”‐derived peanut (Arachis hypogaea) population
Authors: Tseng Yu‐Chien , Tillman Barry L. , Gezan Salvador A. , Wang Jianping , Rowland Diane L. 
Published: July 2018

AbstractSpotted wilt, caused by tomato spotted wilt virus (TSWV), is a major disease of peanut (Arachis hypogaea) in the south‐eastern United States. Cultivar resistance is the most important factor in disease control. However, spotted wilt resistance in current cultivars still carries risk in the absence of other practices when disease is severe. In contrast, a newly developed cultivar, Florida‐EP™ “113,” has demonstrated excellent resistance even when spotted wilt is severe. Information on heritability of this resistance can help breeders better utilize it in breeding. F2‐derived populations from the cross Florida‐EP™ “113”/Georgia Valencia were developed and tested in field experiments in Florida from 2012 to 2014. Disease symptoms were evaluated visually, and the frequency of TSWV infection was measured by ImmunoStrip®. Heritability estimated from ImmunoStrip® was higher (0.66) compared to visual ratings (0.48). Genetic correlations among evaluation methods (rA = 0.92–0.99) and environments (rB = 0.86–0.99) were high. These results indicate that resistance in Florida‐EP™ “113” is highly heritable and that selection in a high disease risk environment is feasible without significant erosion of genetic gain.
Helping to reduce fights before flights: How environmental stressors in organizations shape customer emotions and customer–employee interactions
Authors: DeCelles Katherine A. , DeVoe Sanford E. , Rafaeli Anat , Agasi Shira 
Published: July 2018

AbstractPrevious examinations of environmental stressors in organizations have mostly emphasized their dysfunctional effects on individuals’ emotions and behaviors. Extending this work by drawing from the social functional perspective on emotion, we propose that customers’ negative emotional responses to environmental stressors in organizations can exert both dysfunctional and functional effects on customer–employee interactions. Specifically, we theorize that situational and physiological forms of environmental stressors can be dysfunctional by incurring customer anger, precipitating customer aggression, and diminishing employee helpfulness. We further theorize that situational relative to physiological stressors can exert functional effects in inducing customer fear that elicits empathy and helpfulness from employees. We test our model via an archival, observational, and critical incident yoked experimental study set in the airport context. This research contributes to stress theory and its organizational application by integrating theory from the social functional approach to emotion with appraisal‐based theories of stress in organizations.
Chronic exercise impairs nitric oxide pathway in rabbit carotid and femoral arteries
Authors: Marchio Patricia , Guerra‐Ojeda Solanye , Vila José M. , Aldasoro Martín , Valles Soraya L. , Soler Carlos , Mauricio Maria D. 
Published: July 2018

Key points
Some of the beneficial effects of exercise in preventing vascular related diseases are mediated by the enhancement of endothelial function where the role of nitric oxide (NO) is well documented, although the relevance of calcium activated potassium channels is not fully understood.
The impact of oxidative stress induced by training on endothelial function remains to be clarified.
By evaluating different endothelial vasodilator pathways on two vascular beds in a rabbit model of chronic exercise, we found a decreased NO bioavailability and endothelial nitric oxide synthase expression in both carotid and femoral arteries.
Physical training induced carotid endothelial dysfunction as a result of an increase in oxidative stress and a reduction in superoxide dismutase expression.
In the femoral artery, the lower production of NO was counteracted by an increased participation of large conductance calcium activated potassium channels, preventing endothelial dysfunction.
AbstractThe present study aimed to evaluate the effects of chronic exercise on vasodilator response in two different arteries. Rings of carotid and femoral arteries from control and trained rabbits were suspended in organ baths for isometric recording of tension. Endothelial nitric oxide synthase (eNOS), Cu/Zn and Mn‐superoxide dismutase (SOD), and large conductance calcium activated potassium (BKCa) channel protein expression were measured by western blotting. In the carotid artery, training reduced the relaxation to ACh (10–9 to 3 × 10–6 m) that was reversed by N‐acetylcysteine (10–3 m). l‐NAME (10–4 m) reduced the relaxation to ACh in both groups, although the effect was lower in the trained group (in mean ± SEM, 39 ± 2% vs. 28 ± 3%). Physical training did not modify the relaxation to ACh in femoral arteries, although the response to l‐NAME was lower in the trained group (in mean ± SEM, 41 ± 5% vs. 17 ± 2%). Charybdotoxin (10–7 m) plus apamin (10–6 m) further reduced the maximal relaxation to ACh only in the trained group. The remaining relaxation in both carotid and femoral arteries was abolished by KCl (2 × 10–2 m) and BaCl2 (3 × 10–6 m) plus ouabain (10–4 m) in both groups. Physical training decreased eNOS expression in both carotid and femoral arteries and Cu/Zn and Mn‐SOD expression only in the carotid artery. BKCa channels were overexpressed in the trained group in the femoral artery. In conclusion, chronic exercise induces endothelial dysfunction in the carotid artery as a result of oxidative stress. In the femoral artery, it modifies the vasodilator pathways, enhancing the participation of BKCa channels, thus compensating for the impairment of NO‐mediated vasodilatation.
Impact of car transport availability and drive time on eye examination uptake among adults aged ≥60 years: a record linkage study
Authors: Wright David M , O'Reilly Dermot , Azuara-Blanco Augusto , Hogg Ruth E 
Published: July 2018

AimTo examine associations between uptake of free primary eye care, service availability (density of optometric practices) and service accessibility (household car access and drive time to nearest provider) after accounting for socioeconomic status and other individual, household and area factors.MethodsWe constructed a cohort of 294 870 community-dwelling adults aged 60 years, drawing contextual information from the 2011 Northern Ireland Census. Minimum drive times to the nearest optometry practice (1–19 min) and number of practices were derived for 890 geographical areas. The primary outcome was attendance at one or more publicly funded eye examinations to which all cohort members were entitled between 2009 and 2014. We used multiple log-binomial regression to estimate associations between eye care uptake, car ownership and drive time.ResultsEye examination uptake was 60.0%. 23.7% of the cohort had no car access, and these individuals had lower uptake than car owners (unadjusted risk ratio (RR) of uptake=0.86 (0.86, 0.87)). Among non-car owners, uptake decreased with drive time (longest vs shortest: RR=0.92 (0.88, 0.97)) with the largest decrease at 4 min drive time (approximately 1.5 miles). This pattern was weaker among car owners. These associations were independent of service availability, which was not associated with uptake.ConclusionBoth drive time and household car access were associated with eye care use, adjusting for individual, household and area factors. Policies to improve uptake should target those with no car access, especially those beyond walking distance from the nearest eye care provider.
Effect of thermoelectric material of Ca or Fe-doped LaCoO3
Authors: Murai Kei-Ichiro , Kori Shuhei , Nakai Shun , Moriga Toshihiro 
Published: July 2018

As the Perovskite-type Lanthanum Cobalt Oxide of LaCoO3 is nontoxic and thermally stable even at high temperature, this material is expected as a candidate for thermoelectric applications. The thermoelectric performance of a material is often evaluated by the dimensionless figure-of-merit, ZT (=S[Formula: see text]T/[Formula: see text]), or S[Formula: see text] in the ZT equation. S[Formula: see text] shows the electrical characteristic as a Power factor (PF). It has been reported Seebeck coefficient of LaCoO3 is higher than other oxide materials at room temperature even though electrical conductivity and ZT are lower values. In this study, calcium-doped lanthanum cobaltite La[Formula: see text]Ca[Formula: see text]CoO3 (x = 0.00, 0.05, 0.10 and 0.15) and iron-doped lanthanum cobaltite LaCo[Formula: see text]Fe[Formula: see text]O3 (y = 0.05, 0.10 and 0.15) have been prepared by solid-phase process. The X-ray diffraction patterns of the calcium-doped samples and iron-doped samples show cubic perovskite structure. Electric conductivities were improved by Ca or Fe substitution and showed a tendency to increase with increasing the temperature. The sample substituted with Fe 5 mol.% showed the maximum PF, 0.510 ([Formula: see text] W/K2m) at 548 K, and the sample substituted with Ca 15 mol.% showed the maximum PF, 0.152 ([Formula: see text] W/K2m) at 498 K.
The Epigenomic Landscape of Pituitary Adenomas Reveals Specific Alterations and Differentiates Among Acromegaly, Cushing's Disease and Endocrine-Inactive Subtypes
Authors: Salomon Matthew P. , Wang Xiaowen , Marzese Diego M. , Hsu Sandy C. , Nelson Nellie , Zhang Xin , Matsuba Chikako , Takasumi Yuki , Ballesteros-Merino Carmen , Fox Bernard A. , Barkhoudarian Garni , Kelly Daniel F. , Hoon Dave S.B. 
Published: July 2018

Abstract
Purpose: Pituitary adenomas are one of the most common benign neoplasms of the central nervous system. Although emerging evidence suggests roles for both genetic and epigenetic factors in tumorigenesis, the degree to which these factors contribute to disease remains poorly understood.
Experimental Design: A multiplatform analysis was performed to identify the genomic and epigenomic underpinnings of disease among the three major subtypes of surgically resected pituitary adenomas in 48 patients: growth hormone (GH)–secreting (n = 17), adrenocorticotropic hormone (ACTH)–secreting (n = 13, including 3 silent-ACTH adenomas), and endocrine-inactive (n = 18). Whole-exome sequencing was used to profile the somatic mutational landscape, whole-transcriptome sequencing was used to identify disease-specific patterns of gene expression, and array-based DNA methylation profiling was used to examine genome-wide patterns of DNA methylation.
Results: Recurrent single-nucleotide and small indel somatic mutations were infrequent among the three adenoma subtypes. However, somatic copy-number alterations (SCNA) were identified in all three pituitary adenoma subtypes. Methylation analysis revealed adenoma subtype-specific DNA methylation profiles, with GH-secreting adenomas being dominated by hypomethylated sites. Likewise, gene-expression patterns revealed adenoma subtype-specific profiles. Integrating DNA methylation and gene-expression data revealed that hypomethylation of promoter regions are related with increased expression of GH1 and SSTR5 genes in GH-secreting adenomas and POMC gene in ACTH-secreting adenomas. Finally, multispectral IHC staining of immune-related proteins showed abundant expression of PD-L1 among all three adenoma subtypes.
Conclusions: Taken together, these data stress the contribution of epigenomic alterations to disease-specific etiology among adenoma subtypes and highlight potential targets for future immunotherapy-based treatments. This article reveals novel insights into the epigenomics underlying pituitary adenomas and highlights how differences in epigenomic states are related to important transcriptome alterations that define adenoma subtypes. Clin Cancer Res; 24(17); 4126–36. ©2018 AACR.
Parallel Accumulation of Tumor Hyaluronan, Collagen, and Other Drivers of Tumor Progression
Authors: Li Xiaoming , Shepard H. Michael , Cowell Jessica A. , Zhao Chunmei , Osgood Ryan J. , Rosengren Sanna , Blouw Barbara , Garrovillo Sheryl A. , Pagel Mark D. , Whatcott Clifford J. , Han Haiyong , Von Hoff Daniel D. , Taverna Darin M. , LaBarre Michael J. , Maneval Daniel C. , Thompson Curtis B. 
Published: July 2018

AbstractPurpose: The tumor microenvironment (TME) evolves to support tumor progression. One marker of more aggressive malignancy is hyaluronan (HA) accumulation. Here, we characterize biological and physical changes associated with HA-accumulating (HA-high) tumors.Experimental Design: We used immunohistochemistry, in vivo imaging of tumor pH, and microdialysis to characterize the TME of HA-high tumors, including tumor vascular structure, hypoxia, tumor perfusion by doxorubicin, pH, content of collagen. and smooth muscle actin (α-SMA). A novel method was developed to measure real-time tumor-associated soluble cytokines and growth factors. We also evaluated biopsies of murine and pancreatic cancer patients to investigate HA and collagen content, important contributors to drug resistance.Results: In immunodeficient and immunocompetent mice, increasing tumor HA content is accompanied by increasing collagen content, vascular collapse, hypoxia, and increased metastatic potential, as reflected by increased α-SMA. In vivo treatment of HA-high tumors with PEGylated recombinant human hyaluronidase (PEGPH20) dramatically reversed these changes and depleted stores of VEGF-A165, suggesting that PEGPH20 may also diminish the angiogenic potential of the TME. Finally, we observed in xenografts and in pancreatic cancer patients a coordinated increase in HA and collagen tumor content.Conclusions: The accumulation of HA in tumors is associated with high tIP, vascular collapse, hypoxia, and drug resistance. These findings may partially explain why more aggressive malignancy is observed in the HA-high phenotype. We have shown that degradation of HA by PEGPH20 partially reverses this phenotype and leads to depletion of tumor-associated VEGF-A165. These results encourage further clinical investigation of PEGPH20. Clin Cancer Res; 24(19); 4798–807. ©2018 AACR.