Publications by authors named "Hiroshi Ohta"

211 Publications

PD-L1 immunohistochemistry for canine cancers and clinical benefit of anti-PD-L1 antibody in dogs with pulmonary metastatic oral malignant melanoma.

NPJ Precis Oncol 2021 Feb 12;5(1):10. Epub 2021 Feb 12.

Department of Advanced Pharmaceutics, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, Japan.

Immunotherapy targeting programmed cell death 1 (PD-1) and PD-ligand 1 (PD-L1) represents promising treatments for human cancers. Our previous studies demonstrated PD-L1 overexpression in some canine cancers, and suggested the therapeutic potential of a canine chimeric anti-PD-L1 monoclonal antibody (c4G12). However, such evidence is scarce, limiting the clinical application in dogs. In the present report, canine PD-L1 expression was assessed in various cancer types, using a new anti-PD-L1 mAb, 6C11-3A11, and the safety and efficacy of c4G12 were explored in 29 dogs with pulmonary metastatic oral malignant melanoma (OMM). PD-L1 expression was detected in most canine malignant cancers including OMM, and survival was significantly longer in the c4G12 treatment group (median 143 days) when compared to a historical control group (n = 15, median 54 days). In dogs with measurable disease (n = 13), one dog (7.7%) experienced a complete response. Treatment-related adverse events of any grade were observed in 15 dogs (51.7%). Here we show that PD-L1 is a promising target for cancer immunotherapy in dogs, and dogs could be a useful large animal model for human cancer research.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41698-021-00147-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7881100PMC
February 2021

Association between maternity harassment and depression during pregnancy amid the COVID-19 state of emergency.

J Occup Health 2021 Jan;63(1):e12196

Department of Public Health, Kitasato University School of Medicine, Kanagawa, Japan.

Objectives: Maternity harassment, known in English as pregnancy discrimination, remains prevalent in developed countries. However, research examining the mental health effects of maternity harassment is lacking. We aimed to examine the association between maternity harassment and depression during pregnancy in Japan.

Methods: A cross-sectional Internet survey was conducted on 359 pregnant employees (including women who were working at the time their pregnancy was confirmed) from May 22 to May 31, 2020, during which time a COVID-19 state of emergency was declared. Maternity harassment was defined as being subjected to any of the 16 adverse treatments prohibited by national guidelines. Depression was defined as a score of ≥9 on the Edinburgh Postnatal Depression Scale (Japanese version). Logistic regression analysis was performed.

Results: Overall, 24.8% of the pregnant employees had experienced maternity harassment by supervisors and/or colleagues. After adjusting for demographics, pregnancy status, work status, and fear of COVID-19, pregnant employees who experienced maternity harassment were more likely to have depression than those who did not (odds ratio 2.48, 95% confidential interval 1.34-4.60). This association was not influenced by whether they were teleworking or not as a COVID-19 measure.

Conclusions: One quarter of pregnant employees experienced maternity harassment and had a higher prevalence of depression than those who did not. Being physically away from the office through teleworking may not reduce the effect of maternal harassment on depression. To protect the mental health and employment of pregnant women, employers should comply with the laws and take measures to prevent maternity harassment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/1348-9585.12196DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7815681PMC
January 2021

Echocardiographic estimation of left ventricular-arterial coupling in dogs with myxomatous mitral valve disease.

J Vet Intern Med 2021 Jan 13;35(1):78-87. Epub 2021 Jan 13.

Laboratory of Veterinary Internal Medicine, Department of Veterinary Clinical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Hokkaido, Japan.

Background: The effective arterial elastance (Ea) to left ventricular (LV) end-systolic elastance (Ees) ratio (Ea/Ees) is an index of the interaction between LV and systemic arterial systems, left ventricular-arterial coupling (VAC). The Ea is an index of total arterial load of the LV, whereas Ees is an index of LV systolic function. In humans, inappropriate VAC based on increased Ea/Ees estimated using echocardiography is associated with more advanced heart disease severity.

Hypothesis: Left ventricular-arterial coupling assessed by echocardiographic estimation of Ea/Ees is associated with disease severity in dogs with myxomatous mitral valve disease (MMVD).

Animals: Ninety MMVD dogs and 61 healthy dogs.

Methods: Prospective cross-sectional study. The MMVD dogs were classified into stages B1, B2, or C according to American College of Veterinary Internal Medicine guidelines. Effective arterial elastance was echocardiographically estimated using the formula: mean blood pressure/(forward stroke volume/body weight). End-systolic elastance was echocardiographically estimated using the formula: mean blood pressure/(LV end-systolic volume/body weight). The ratio Ea/Ees was calculated.

Results: The ratio Ea/Ees was higher in stage B2 dogs than in healthy dogs and dogs stage B1 (both P < .0001), and higher in stage C dogs than in healthy dogs and dogs in the other 2 stages (healthy vs C and B1 vs C, P < .0001; B2 vs C, P = .0005). Multivariable logistic regression analysis showed that Ea/Ees and the peak velocity of early diastolic transmitral flow to isovolumic relaxation time ratio were independent predictors of stage C among echocardiographic indices in MMVD dogs.

Conclusions And Clinical Importance: Inappropriate VAC assessed by echocardiographically estimated Ea/Ees is associated with advanced disease severity in dogs with MMVD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jvim.16028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7848320PMC
January 2021

Prognostic value of small intestinal dilatation in dogs with protein-losing enteropathy.

J Vet Med Sci 2021 Jan 12. Epub 2021 Jan 12.

Laboratory of Veterinary Internal Medicine, Graduate School of Veterinary Medicine, Hokkaido University.

To date, little is known about the prognostic significance of ultrasonographic findings in dogs with protein-losing enteropathy (PLE). The aim of this retrospective study was to examine the prognostic value of ultrasonographic findings in dogs with PLE. A total of 26 dogs with PLE were included: 20 dogs with chronic enteropathy and 6 dogs with gastrointestinal lymphoma. The presence of small intestinal dilatation was associated with shorter survival time in dogs with PLE (P=0.003). The presence of hyperechoic intestinal mucosal striations was associated with longer survival time in dogs with PLE (P=0.0085). The results of the current study indicate that the presence of small intestinal dilatation might be associated with poor prognosis in dogs with PLE.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1292/jvms.20-0489DOI Listing
January 2021

Cyclosporin A and FGF signaling support the proliferation/survival of mouse primordial germ cell-like cells in vitro†.

Biol Reprod 2021 Feb;104(2):344-360

Institute for the Advanced Study of Human Biology (ASHBi), Kyoto University, Kyoto, Japan.

Primordial germ cells (PGCs) are the founding population of the germ cell lineage that undergo a multistep process to generate spermatozoa or oocytes. Establishing an appropriate culture system for PGCs is a key challenge in reproductive biology. By a chemical screening using mouse PGC-like cells (mPGCLCs), which were induced from mouse embryonic stem cells, we reported previously that forskolin and rolipram synergistically enhanced the proliferation/survival of mPGCLCs with an average expansion rate of ~20-fold. In the present study, we evaluated other chemicals or cytokines to see whether they would improve the current mPGCLC culture system. Among the chemicals and cytokines examined, in the presence of forskolin and rolipram, cyclosporin A (CsA) and fibroblast growth factors (FGFs: FGF2 and FGF10) effectively enhanced the expansion of mPGCLCs in vitro (~50-fold on average). During the expansion by CsA or FGFs, mPGCLCs comprehensively erased their DNA methylation to acquire a profile equivalent to that of gonadal germ cells in vivo, while maintaining their highly motile phenotype as well as their transcriptional properties as sexually uncommitted PGCs. Importantly, these mPGCLCs robustly contributed to spermatogenesis and produced fertile offspring. Furthermore, mouse PGCs (mPGCs) cultured with CsA ex vivo showed transcriptomes and DNA methylomes similar to those of cultured mPGCLCs. The improved culture system for mPGCLCs/mPGCs would be instructive for addressing key questions in PGC biology, including the mechanisms for germ cell migration, epigenetic reprogramming, and sex determination of the germline.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/biolre/ioaa195DOI Listing
February 2021

Formation of Calcified Nodule as a Cause of Early In-Stent Restenosis in Patients Undergoing Dialysis.

J Am Heart Assoc 2020 10 23;9(19):e016595. Epub 2020 Sep 23.

Department of Cardiology Kindai University Osaka Japan.

Background Dialysis is an independent risk factor for in-stent restenosis (ISR) after stent implantation in coronary arteries. However, the characteristics of ISR in patients undergoing dialysis remain unclear, as there are no histological studies evaluating the causes of this condition. The aim of the present study was to investigate the causes of ISR between patients who are undergoing dialysis and those who are not by evaluating tissues obtained from ISR lesions using directional coronary atherectomy. Methods and Results A total of 29 ISR lesions from 29 patients included in a multicenter directional coronary atherectomy registry of 128 patients were selected for analysis and divided into a dialysis group (n=8) and a nondialysis group (n=21). Histopathological evaluation demonstrated that an in-stent calcified nodule was a major histological characteristic of ISR lesions in the dialysis group and the prevalence of an in-stent calcified nodule was significantly higher in the dialysis group compared with the nondialysis group (75% versus 5%, respectively; <0.01). On the other hand, the prevalence of an in-stent lipid-rich plaque was significantly lower in the dialysis group compared with the nondialysis group (0% versus 43%, respectively; =0.03). In all cases with an in-stent calcified nodule, the underlying calcification before stent implantation was moderate to severe. When tissue characteristics were stratified according to duration post-stent implantation, an in-stent calcified nodule in the dialysis group was mainly observed within 1 year after stent implantation. Conclusions In-stent calcified nodules are a common cause of ISR in patients undergoing dialysis and are observed within 1 year after stent implantation, suggesting different causes of ISR between patients undergoing dialysis and those who are not.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/JAHA.120.016595DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7792410PMC
October 2020

Long-term expansion with germline potential of human primordial germ cell-like cells in vitro.

EMBO J 2020 Nov 20;39(21):e104929. Epub 2020 Sep 20.

Institute for the Advanced Study of Human Biology (ASHBi), Kyoto University, Kyoto, Japan.

Human germ cells perpetuate human genetic and epigenetic information. However, the underlying mechanism remains elusive, due to a lack of appropriate experimental systems. Here, we show that human primordial germ cell-like cells (hPGCLCs) derived from human-induced pluripotent stem cells (hiPSCs) can be propagated to at least ~10 -fold over a period of 4 months under a defined condition in vitro. During expansion, hPGCLCs maintain an early hPGC-like transcriptome and preserve their genome-wide DNA methylation profiles, most likely due to retention of maintenance DNA methyltransferase activity. These characteristics contrast starkly with those of mouse PGCLCs, which, under an analogous condition, show a limited propagation (up to ~50-fold) and persist only around 1 week, yet undergo cell-autonomous genome-wide DNA demethylation. Importantly, upon aggregation culture with mouse embryonic ovarian somatic cells in xenogeneic-reconstituted ovaries, expanded hPGCLCs initiate genome-wide DNA demethylation and differentiate into oogonia/gonocyte-like cells, demonstrating their germline potential. By creating a paradigm for hPGCLC expansion, our study uncovers critical divergences in expansion potential and the mechanism for epigenetic reprogramming between the human and mouse germ cell lineage.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.15252/embj.2020104929DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7604613PMC
November 2020

Gene expression of leucine-rich alpha-2 glycoprotein in the polypoid lesion of inflammatory colorectal polyps in miniature dachshunds.

J Vet Med Sci 2020 Oct 5;82(10):1445-1449. Epub 2020 Aug 5.

Laboratory of Veterinary Internal Medicine, Graduate School of Veterinary Medicine, Hokkaido University, N18 W9, Kita-ku, Sapporo, Hokkaido 060-0818, Japan.

Inflammatory colorectal polyps (ICRPs) in miniature dachshunds (MDs) are speculated to be a breed-specific inflammatory bowel disease (IBD). Leucine-rich alpha-2 glycoprotein (LRG) has been identified as a novel biomarker of human IBD. The aim of this study was to examine LRG gene expression in the polypoid lesions of ICRPs. Polypoid lesion specimens were collected from 24 MDs with ICRPs. Nonpolypoid colonic mucosa was collected from 18 MDs with ICRPs and 10 controls. The gene expression of LRG, interleukin (IL)-1β, IL-6, tumor necrosis factor-α, and IL-22 was examined. The expression of LRG gene was significantly increased in the polypoid lesions of ICRPs and correlated with that of the four cytokines. In conclusion, the LRG gene was expressed within the polypoid lesions of ICRPs and might be associated with local cytokine expression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1292/jvms.20-0242DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7653302PMC
October 2020

Activities of matrix metalloproteinase-2, matrix metalloproteinase-9, and serine proteases in samples of the colorectal mucosa of Miniature Dachshunds with inflammatory colorectal polyps.

Am J Vet Res 2020 Jul;81(7):572-580

Objective: To investigate the activities of gelatinases (matrix metalloproteinase [MMP]-2 and MMP-9) and serine proteases in the colorectal mucosa of Miniature Dachshunds (MDs) with inflammatory colorectal polyps (ICRPs).

Animals: 15 MDs with ICRPs and 5 dogs with non-ICRP-related large bowel diarrhea (controls).

Procedures: Zymographic methods were used to evaluate the activities of MMP-2, MMP-9, latent forms of MMP-2 and MMP-9 (pro-MMP-2 and pro-MMP-9), and serine proteases in inflamed and noninflamed tissue samples from MDs with ICRPs and in noninflamed tissue samples from control dogs. The associations of serine protease activities with MMP-2 or MMP-9 activity were also analyzed.

Results: Activities of pro-MMP-2 and pro-MMP-9 were detected in most tissue samples, regardless of the tissue type, whereas activities of MMP-2 and MMP-9 were not detected in control tissue samples. In the inflamed tissue samples from MDs with ICRPs, the activities of MMP-2, pro-MMP-9, and MMP-9 were significantly higher than those in the noninflamed tissue samples from those dogs. Serine protease activities were significantly higher in the inflamed and noninflamed tissue samples from MDs with ICRP, compared with findings for control tissue samples. A weak correlation was detected between serine protease activities and MMP-9 activity.

Conclusions And Clinical Relevance: Study results suggested that gelatinase and serine protease activities are upregulated in the colorectal mucosa of MDs with ICRPs, possibly contributing to the pathogenesis of this disease through the functions of these enzymes in degradation of extracellular matrix and promotion of inflammatory cell migration and inflammatory responses.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2460/ajvr.81.7.572DOI Listing
July 2020

An area ratio of thyroid gland to common carotid artery for evaluating the thyroid gland size.

J Vet Med Sci 2020 Jul 4;82(7):1012-1016. Epub 2020 Jun 4.

Laboratory of Veterinary Internal Medicine, Department of Clinical Sciences, Faculty of Veterinary Medicine, Hokkaido University, Kita 18-jo Nishi 9-chome, Kita-ku, Sapporo 060-0818, Japan.

The feasibility of ultrasonographic measurement of thyroid gland area to common carotid artery (TG:CCA) was investigated. Twenty-one healthy, 12 hypothyroid and 18 non-thyroid illness (NTI) dogs were evaluated. The area of thyroid lobe and common carotid artery in right and left sides were measured using the same ultrasonographic images in transverse plane. The average of the right and left ratio was calculated as TG:CCA. The median TG:CCA of 21 healthy dogs was 1.53, and it did not correlate either body weight or age. The median TG:CCA of 12 hypothyroid dogs was 0.81, which was significantly lower than that of 18 NTI dogs (1.81, P<0.001). If the cut off value <1.12 was used, TG:CCA indicated hypothyroidism with a sensitivity of 100%, specificity of 83%, and accuracy of 90%. Our data indicated that TG:CCA was independent of both body weight, which may contribute to consistent measurement of thyroid size. The results of this study suggest that TG:CCA is a promising tool for diagnosing canine hypothyroidism.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1292/jvms.20-0183DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7399328PMC
July 2020

Genome-wide DNA methylation analysis in canine gastrointestinal lymphoma.

J Vet Med Sci 2020 May 25;82(5):632-638. Epub 2020 Mar 25.

Laboratory of Veterinary Internal Medicine, Graduate School of Veterinary Medicine, Hokkaido University, N18 W9, Kita-ku, Sapporo, Hokkaido 060-0818, Japan.

DNA methylation is the covalent modification of methyl groups to DNA mostly at CpG dinucleotides and one of the most studied epigenetic mechanisms that leads to gene expression variability without affecting the DNA sequence. Genome-wide analysis of DNA methylation identified the signatures that could define subtypes of human lymphoma patients. The objective of this study was to conduct the genome-wide analysis of DNA methylation in dogs with gastrointestinal lymphoma (GIL). Genomic DNA was extracted from endoscopic biopsies from 10 dogs with GIL. We performed Digital Restriction Enzyme Assay of DNA Methylation (DREAM) for genome-wide DNA methylation analysis that could provide highly quantitative information on DNA methylation levels of CpG sites across the dog genome. We successfully obtained data of quantitative DNA methylation level for 148,601-162,364 CpG sites per GIL sample. Next, we analyzed 83,132 CpG sites to dissect the differences in DNA methylation between GIL and normal peripheral blood mononuclear cells (PBMCs). We found 383-3,054 CpG sites that were hypermethylated in GIL cases compared to PBMCs. Interestingly, 773 CpG sites including promoter regions of 61 genes were identified to be commonly hypermethylated in more than half of the cases, suggesting conserved DNA methylation patterns that are abnormal in GIL. This study revealed that there was a large number of hypermethylated sites that are common in most of canine GIL. These abnormal DNA methylation could be involved in tumorigenesis of the canine GIL.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1292/jvms.19-0547DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7273592PMC
May 2020

One-year limb outcome and mortality in patients undergoing revascularization therapy for acute limb ischemia: short-term results of the Edo registry.

Cardiovasc Interv Ther 2020 Mar 25. Epub 2020 Mar 25.

Division of Cardiovascular Medicine, Toho University Ohashi Medical Center, Tokyo, Japan.

The present study aimed to clarify the current status, therapeutic strategy, and 1-year outcome in acute limb ischemia (ALI) patients in Japan. The EnDOvascular treatment (Edo) registry database includes 324 patients from 10 institutes who were registered between November 2011 and October 2013. A total of 70 ALI patients (mean age 74.0 years) from the Edo registry database were enrolled in this study. Of the 70 included patients, 72.9% were male and 35.7% had embolism. Of patients, 38.6%, 42.9%, and 18.6% underwent EVT, surgery, and hybrid thrombectomy, respectively, in primary revascularization strategy. Limb ischemia was categorized into four classes at initial evaluation: SVS/ISCVS class I (n = 13, 18.6%), SVS/ISCVS class IIa (n = 36, 51.4%), SVS/ISCVS class IIb (n = 21, 30%), and SVS/ISCVS class III (n = 0, 0%). Three patients with SVS/ISCVS class IIb limb ischemia developed myonephropathic metabolic syndrome. No catheter-directed thrombolysis was employed as a primary revascularization strategy. The 1-year rates of all-cause death, major amputation, and a composite of perioperative death or major adverse limb event were 28.6%, 5.7%, and 40.0%, respectively. Lower age, male sex, dyslipidemia, high estimated glomerular filtration rate, high albumin level, and low C-reactive protein level were independent positive predictors of all-cause death. In this registry, SVS/ISCVS class IIa ALI was predominant. Approximately 40% of primary revascularization strategy was surgery and EVT, followed by hybrid therapy. All-cause death and major amputation rates at 1 year were less than 30% and 6%, respectively.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12928-020-00662-6DOI Listing
March 2020

Clinical characteristics of dogs with food-responsive protein-losing enteropathy.

J Vet Intern Med 2020 Mar 15;34(2):659-668. Epub 2020 Feb 15.

Laboratory of Veterinary Internal Medicine, Department of Clinical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Hokkaido, Japan.

Background: In dogs with protein-losing enteropathy (PLE), data on the clinical characteristics of food-responsive PLE (FR-PLE) remain scarce.

Objective: To determine the clinical characteristics of FR-PLE in dogs responsive to ultralow-fat diet (ULFD) management.

Animals: Thirty-three dogs diagnosed with PLE based on standard diagnostic criteria.

Methods: Retrospective review of medical records. Clinical findings were compared between dogs with FR-PLE (FR-PLE group) and those with immunosuppressant-responsive PLE (IR-PLE) or nonresponsive PLE (NR-PLE) (IR/NR-PLE group). The area under the curve (AUC) of a receiver operating characteristic curve was used to evaluate the ability of factors to differentiate the FR-PLE and IR/NR-PLE groups. Survival time was compared between the FR-PLE and IR/NR-PLE groups.

Results: Twenty-three dogs responded to ULFD management and were diagnosed with FR-PLE. The canine chronic enteropathy clinical activity index (CCECAI) was significantly lower in the FR-PLE group than in the IR/NR-PLE group (P < .001). The AUC of CCECAI for differentiating the FR-PLE group was 0.935 (95% confidence interval [CI], 0.845-1.000) with an optimal cutoff value of 8 (sensitivity, 0.826; specificity, 0.889). Survival times were significantly longer in the FR-PLE group (median, not reached) than in the IR/NR-PLE group (median, 432 days; P < .001).

Conclusions And Clinical Importance: Dogs that respond to ULFD management and are diagnosed with FR-PLE are expected to have a favorable prognosis. Clinical scores, specifically the CCECAI, could be useful for differentiating FR-PLE from IR-PLE or NR-PLE.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jvim.15720DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7096654PMC
March 2020

ZGLP1 is a determinant for the oogenic fate in mice.

Science 2020 03 13;367(6482). Epub 2020 Feb 13.

Institute for the Advanced Study of Human Biology (ASHBi), Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.

Sex determination of germ cells is vital to creating the sexual dichotomy of germ cell development, thereby ensuring sexual reproduction. However, the underlying mechanisms remain unclear. Here, we show that ZGLP1, a conserved transcriptional regulator with GATA-like zinc fingers, determines the oogenic fate in mice. ZGLP1 acts downstream of bone morphogenetic protein, but not retinoic acid (RA), and is essential for the oogenic program and meiotic entry. ZGLP1 overexpression induces differentiation of in vitro primordial germ cell-like cells (PGCLCs) into fetal oocytes by activating the oogenic programs repressed by Polycomb activities, whereas RA signaling contributes to oogenic program maturation and PGC program repression. Our findings elucidate the mechanism for mammalian oogenic fate determination, providing a foundation for promoting in vitro gametogenesis and reproductive medicine.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1126/science.aaw4115DOI Listing
March 2020

Induction of the germ cell fate from pluripotent stem cells in cynomolgus monkeys†.

Biol Reprod 2020 03;102(3):620-638

Institute for the Advanced Study of Human Biology (ASHBi), Kyoto University, Kyoto, Japan.

In vitro reconstitution of germ-cell development from pluripotent stem cells (PSCs) has created key opportunities to explore the fundamental mechanisms underlying germ-cell development, particularly in mice and humans. Importantly, such investigations have clarified critical species differences in the mechanisms regulating mouse and human germ-cell development, highlighting the necessity of establishing an in vitro germ-cell development system in other mammals, such as non-human primates. Here, we show that multiple lines of embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) in cynomolgus monkeys (Macaca fascicularis; cy) can be maintained stably in an undifferentiated state under a defined condition with an inhibitor for WNT signaling, and such PSCs are induced efficiently into primordial germ cell-like cells (PGCLCs) bearing a transcriptome similar to early cyPGCs. Interestingly, the induction kinetics of cyPGCLCs from cyPSCs is faster than that of human (h) PGCLCs from hPSCs, and while the transcriptome dynamics during cyPGCLC induction is relatively similar to that during hPGCLC induction, it is substantially divergent from that during mouse (m) PGCLC induction. Our findings delineate common as well as species-specific traits for PGC specification, creating a foundation for parallel investigations into the mechanism for germ-cell development in mice, monkeys, and humans.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/biolre/ioz205DOI Listing
March 2020

A childhood immunization education program for parents delivered during late pregnancy and one-month postpartum: a randomized controlled trial.

BMC Health Serv Res 2019 Nov 5;19(1):798. Epub 2019 Nov 5.

Department of Family Nursing, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo, 113-0033, Japan.

Background: Improved immunization rates have reduced the incidence of vaccine-preventable diseases (VPDs) in advanced nations. Japan's unique vaccination system classifies vaccines into routine vaccines ostensibly required under the Preventive Vaccination Law and recommended but optional vaccines, although all vaccines are in fact voluntary. In Japan, low immunization rates, particularly for optional vaccines, have resulted in high rates of sequelae and death. The decision as to whether a child will receive a vaccine depends on the parents, who must obtain information, make inquiries, and make the required payment, the last of which is a major barrier. This randomized, controlled trial was conducted to evaluate the effectiveness of an immunization education program designed to meet mothers' needs.

Methods: This randomized controlled trial assigned pregnant women to intervention or control groups. The intervention was individual education sessions involving the children's fathers in shared decision-making on whether or not to immunize their child. A survey was conducted before and after the intervention. Data were analyzed using the intention-to-treat principle.

Results: Of 225 pregnant women, 175 (78%) participated and 171 replied to the post-survey. At age 3 months, intervention infants had higher self-reported immunization rates for hepatitis B virus vaccine (76% vs. 49%; P < 0.001) and rotavirus vaccine (84% vs. 68%; P = 0.019) than control group infants. The percentage of parents intending to vaccinate their infants was higher in the intervention group (77% vs. 52%; P < 0.01). Improvements in scores for basic knowledge (mean [SD]: 5.5 [3.6] vs. 3.0 [3.8], range: 10-30; P < 0.001), advanced knowledge (mean [SD]: 5.1 [2.4] vs. 2.8 [2.5], range: 5-15; P < 0.001), and health literacy regarding immunization (mean [SD]: 0.5 [0.8] vs. 0.2 [0.6], range: 1-5; P < 0.01) were higher in the intervention group. The rate of decision making by both parents (68% vs. 52%; P < 0.05) was higher in the intervention group.

Conclusions: Our findings confirmed the program's effectiveness. The intervention improved immunization rates, the percentage of parents intending to vaccinate their infants and knowledge scores. Interventions which directly and indirectly involved fathers in shared decision-making on whether to immunize their child were effective, as were individualized interventions that provided parents with access to up-to-date information.

Trial Registration: UMIN000012575 . Registered 14 December 2013 (The study was prospectively registered).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12913-019-4622-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6833181PMC
November 2019

Cardiac Rupture Due to Side Branch Occlusion After Stent Implantation - The Crime of Jailed Stent.

Circ J 2020 01 18;84(2):295. Epub 2019 Oct 18.

Division of Human Pathology, Department of Pathology and Microbiology, Nihon University School of Medicine.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1253/circj.CJ-19-0510DOI Listing
January 2020

Computed tomographic features for differentiating benign from malignant liver lesions in dogs.

J Vet Med Sci 2019 Dec 10;81(12):1697-1704. Epub 2019 Oct 10.

Laboratory of Veterinary Internal Medicine, Department of Veterinary Clinical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Hokkaido 060-0818, Japan.

Thus far, there are few computed tomography (CT) characteristics that can distinguish benign and malignant etiologies. The criteria are complex, subjective, and difficult to use in clinical applications due to the high level of experience needed. This study aimed to identify practical CT variables and their clinical relevance for broadly classifying histopathological diagnoses as benign or malignant. In this prospective study, all dogs with liver nodules or masses that underwent CT examination and subsequent histopathological diagnosis were included. Signalments, CT findings and histopathological diagnoses were recorded. Seventy liver nodules or masses in 57 dogs were diagnosed, comprising 18 benign and 52 malignant lesions. Twenty-three qualitative and quantitative CT variables were evaluated using univariate and stepwise multivariate analyses, respectively. Two variables, namely, the postcontrast enhancement pattern of the lesion in the delayed phase (heterogeneous; odds ratio (OR): 14.7, 95% confidence interval (CI): 0.82-262.03, P=0.0429) and the maximal transverse diameter of the lesion (>4.5 cm; OR: 33.3, 95% CI: 2.29-484.18, P=0.0006), were significantly related to the differentiation of benign from malignant liver lesions, with an area under the curve of 0.8910, representing an accuracy of 88.6%. These findings indicate that features from triple-phase CT can provide information for distinguishing pathological varieties of focal liver lesions and for clinical decision making. Evaluations of the maximal transverse diameter and postcontrast enhancement pattern of the lesion included simple CT features for predicting liver malignancy with high accuracy in clinical settings.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1292/jvms.19-0278DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6943317PMC
December 2019

Usefulness of noninvasive shear wave elastography for the assessment of hepatic fibrosis in dogs with hepatic disease.

J Vet Intern Med 2019 Sep 28;33(5):2067-2074. Epub 2019 Aug 28.

Laboratory of Veterinary Internal Medicine, Department of Veterinary Clinical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan.

Background: Two-dimensional shear wave elastography (2D-SWE) can noninvasively evaluate hepatic elastic modulus as shear wave velocity (SWV). Additionally, it may predict the presence of clinical relevant hepatic fibrosis (≥F2) in dogs with hepatic disease.

Objectives: To investigate whether SWV measured by 2D-SWE can differentiate between dogs with (≥F2) and without (F0-1) clinically relevant hepatic fibrosis.

Animals: Twenty-eight client-owned dogs with hepatic disease and 8 normal healthy Beagle dogs were enrolled.

Methods: In this cross-sectional prospective study, SWVs were measured using 2D-SWE in all dogs. Hepatic fibrosis stages and necroinflammatory activity grades were histopathologically evaluated using a histological scoring scheme that was adapted from the Ishak schema used in human medicine.

Results: Median SWVs were significantly higher in dogs with clinically relevant hepatic fibrosis (2.04 m/s; range, 1.81-2.26 m/s) than in healthy dogs (1.51 m/s; range, 1.44-1.66 m/s; P = .007), and dogs without clinically relevant hepatic fibrosis (1.56 m/s; range, 1.37-1.67 m/s; P < .001). However, no significant difference was found in the SWVs between dogs without clinically relevant hepatic fibrosis and healthy dogs (P = .99). Furthermore, median SWVs were not significantly different among dogs with necroinflammatory activity, those without necroinflammatory activity, and healthy dogs (Kruskal-Wallis test, P = .12).

Conclusions And Clinical Importance: The 2D-SWE may be useful for predicting the presence of hepatic fibrosis in dogs with hepatic disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jvim.15598DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6766497PMC
September 2019

Findings of contrast-enhanced ultrasonography with Sonazoid for cholangiocellular adenoma in three dogs.

J Vet Med Sci 2019 Aug 27;81(8):1104-1108. Epub 2019 Jun 27.

Laboratory of Veterinary Internal Medicine, Department of Veterinary Clinical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Hokkaido 060-0818, Japan.

Contrast-enhanced ultrasonography (CEUS) is useful to distinguish benign and malignant focal liver lesions in dogs. Cholangiocellular adenoma is an extremely rare benign tumor in dogs and has not been examined using CEUS with Sonazoid. The aim of this study was to describe findings of CEUS with Sonazoid in three dogs with cholangiocellular adenoma. All three dogs showed contrast defects in the Kupffer phase and these findings mimicked malignant neoplasia during the Kupffer phase. Moreover, all dogs showed early washout and hypoechoic lesions relative to the surrounding normal liver parenchyma in the portal phase. To our knowledge, this is the first study to report that CEUS findings of cholangiocellular adenoma with Sonazoid mimicked malignancy in three dogs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1292/jvms.19-0116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6715911PMC
August 2019

Plasma amino acid profiles in dogs with inflammatory bowel disease.

J Vet Intern Med 2019 Jul 20;33(4):1602-1607. Epub 2019 May 20.

Laboratory of Veterinary Internal Medicine, Department of Veterinary Clinical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Hokkaido, Japan.

Background: Lymphocytic-plasmacytic enteritis is the common form of idiopathic inflammatory bowel disease (IBD) in dogs. In human IBD, disturbances of amino acid metabolism have been demonstrated to be involved in the pathophysiology of IBD. Therefore, plasma amino acid profile might represent a novel marker of human IBD.

Objectives: To determine the plasma amino acid profiles of dogs with IBD and its usefulness as a novel marker of IBD in dogs.

Animals: Fasting blood plasma was obtained from 10 dogs with IBD and 12 healthy dogs.

Methods: All IBD dogs were prospectively included in this study, and heparinized blood samples were collected. The plasma concentrations of 21 amino acids were determined using the ninhydrin method. The relationships among the plasma amino acid concentrations and plasma C-reactive protein (CRP) concentration, canine chronic enteropathy clinical activity index (CCECAI), and overall World Small Animal Veterinary Association (WSAVA) score were investigated.

Results: Median concentration (nmol/mL) of methionine [46.2; range, 30.0-59.3], proline [119.4; range, 76.7-189.2], serine [115.1; range, 61.4-155.9], and tryptophan [17.4; range, 11.9-56.3]) were significantly lower than in control dogs [62.6; range, 51.0-83.6, 199.1; range, 132.5-376.7, 164.3; range, 124.7-222.9, and 68.3; range, 35.7-94.8, respectively]. A negative correlation was identified between the plasma serine concentration and CCECAI (r = -.67, P = .03), but there were no correlations between plasma amino acid concentrations and CRP concentration or overall WSAVA score.

Conclusions And Clinical Importance: Plasma serine concentration might represent a novel maker of IBD in dogs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jvim.15525DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6639477PMC
July 2019

Effect of acute volume loading on left atrial strain values derived from two-dimensional speckle tracking echocardiography in dogs.

J Vet Med Sci 2019 Jul 15;81(7):949-957. Epub 2019 May 15.

Laboratory of Veterinary Internal Medicine, Graduate School of Veterinary Medicine, Hokkaido University, Hokkaido 006-0818, Japan.

The purpose of this study was to evaluate the cardiac acute volume loading effect on left atrial (LA) strain and strain rate (SR) parameters derived from two-dimensional speckle tracking echocardiography (2D-STE) in healthy dogs. Six healthy beagles were anesthetized and subjected to increase cardiac preload by intravenous infusion with lactated Ringer solution at 150 ml/kg/hr for 90 min. A Swan-Ganz catheter was placed to directly measure the mean pulmonary capillary wedge pressure (PCWP). Echocardiography was performed before (baseline) and at 15, 30, 45, 60, 75, and 90 min after acute volume loading began. Apical 4-chamber images focused on the LA were digitally recorded for later strain and SR analysis via 2D-STE. Acute volume loading significantly increased from baseline during LA strain and SR as assessed by the speckle tracking-based technique during reservoir and conduit function at 15 to 90 min after volume load began, and strain indices representing booster pump function were enhanced at 45 to 90 min. In addition, acute volume loading resulted in a significantly greater PCWP after fluid infusion. On multiple regression analysis, quadratic regression analysis was a better fit for the relationship between PCWP and all LA functional indices. Our findings indicated that LA function analyzed by strain and SR was enhanced during cardiac acute volume loading in healthy dogs. The change in strain and SR during acute volume loading should be interpreted with caution during the diagnosis of heart diseases related to volume overload.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1292/jvms.19-0012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6656807PMC
July 2019

Plasma-free amino acid profiles in dogs with hepatocellular carcinoma.

J Vet Intern Med 2019 Jul 8;33(4):1653-1659. Epub 2019 May 8.

Laboratory of Veterinary Internal Medicine, Department of Veterinary Clinical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan.

Background: Metabolomic analysis using blood samples has been suggested to be useful for the early detection of cancer. Among metabolites, plasma-free amino acid (PFAA) profiles are potential diagnostic biomarkers for several diseases including cancer. However, the relationship between PFAA concentrations and liver tumors in dogs remains unknown.

Objective: To determine the characteristics of PFAA profiles of dogs with hepatocellular carcinoma (HCC) and correlated clinical features.

Animals: Thirty-four client-owned dogs diagnosed with HCC (n = 26) and benign liver diseases (n = 8) and 11 age-matched healthy dogs.

Methods: Prospective study using heparinized blood samples from fasted dogs. Plasma was deproteinized, and the concentrations of 21 amino acids were measured using an automated high-performance liquid chromatography amino acid analyzer.

Results: Plasma glutamic acid concentrations were significantly different among groups (P < .0024 after Bonferroni correction). Compared to healthy dogs, dogs with HCC and benign liver diseases had significantly higher concentrations of glutamic acid by post hoc analysis. However, no significant difference in the PFAA profiles of HCC and benign liver diseases were detected. In addition, preoperative and postoperative PFAA profiles of dogs with HCC were not significantly different.

Conclusions And Clinical Importance: Increased glutamic acid concentrations might play a role in the development or be a consequence of liver tumor formation. However, PFAA profiles of HCC could not be differentiated from those of benign lesions. In addition, glutamic acid concentrations did not change after surgical resection. These results indicate that PFAA profiles may not be useful biomarkers for detecting HCC in dogs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jvim.15512DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6639499PMC
July 2019

Predictive factors of malignancy in dogs with focal liver lesions using clinical data and ultrasonographic features.

J Vet Med Sci 2019 May 8;81(5):723-729. Epub 2019 Apr 8.

Laboratory of Veterinary Internal Medicine, Department of Veterinary Clinical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Hokkaido 060-0818, Japan.

A definitive diagnosis of focal liver lesions (FLLs) requires invasive procedures for histopathologic examination. Thus, a simpler noninvasive diagnostic method, such as conventional ultrasonography combined with clinical data, is needed for the prediction of liver malignancy. The objective of this study was to examine the diagnostic accuracy of clinical data and ultrasonographic (US) features to differentiate benign and malignant liver lesions. Medical records and US images from dogs with FLLs that underwent abdominal US and histopathologic examinations following surgery or liver biopsy were retrospectively reviewed. Clinical data, including signalment, clinical signs and laboratory findings, and the US features of liver lesions that could act as predictive factors were assessed using univariate and multivariate analyses to evaluate the associations between predictive factors and liver malignancy. Based on the histopathologic results, 55 dogs with malignant lesions and 28 dogs with benign lesions were included in the study. The results of univariate analysis showed that several US features and platelet count were significantly associated with liver malignancy. Multivariate analysis revealed that the platelet count (thrombocytosis; odds ratio [OR]: 4.13, 95% confidence intervals [CI]: 1.81-9.41), lesion size (4.1 cm or greater; OR: 23.83, 95% CI: 3.74-151.95) and echotexture of FLLs (heterogenous; OR: 8.44; 95% CI: 1.37-51.91) were independent predictors for differentiating benign and malignant liver lesions, suggesting that a combination of clinical data and US findings of FLLs could predict liver malignancy in dogs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1292/jvms.18-0673DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6541846PMC
May 2019

Evaluation of liver and spleen stiffness of healthy dogs by use of two-dimensional shear wave elastography.

Am J Vet Res 2019 Apr;80(4):378-384

Objective: To assess liver and spleen stiffness in healthy dogs by use of a novel 2-D shear wave elastography (SWE) technique and to investigate the repeatability and reproducibility of the technique.

Animals: 8 healthy adult Beagles.

Procedures: 2-D SWE was performed on each dog to assess liver and spleen stiffness. Repeatability (intraday variability) and reproducibility (interday variability) of 2-D SWE were investigated. For all 8 dogs, 2-D SWE was performed 3 times in 1 day (4-hour intervals) and on 3 separate days (1-week interval). Data were expressed as mean ± SD values for shear wave velocity and the Young modulus in the liver and spleen. Intraday and interday coefficients of variation were assessed for all variables.

Results: Mean ± SD shear wave velocity obtained for the liver and spleen was 1.51 ± 0.08 m/s and 2.18 ± 0.27 m/s, respectively. Mean value for the Young modulus obtained for the liver and spleen was 6.93 ± 0.79 kPa and 14.66 ± 3.79 kPa, respectively. Elasticity values were significantly higher for the spleen than for the liver. Intraday and interday coefficients of variation for all variables were < 25% (range, 3.90% to 20.70%).

Conclusions And Clinical Relevance: 2-D SWE was a feasible technique for assessing liver and spleen stiffness of healthy dogs. Future studies on the application of 2-D SWE for dogs with chronic hepatitis, cirrhosis, and portal hypertension are needed to evaluate the clinical applicability of 2-D SWE.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2460/ajvr.80.4.378DOI Listing
April 2019

Th17 cells increase during maturation in peripheral blood of healthy dogs.

Vet Immunol Immunopathol 2019 Mar 5;209:17-21. Epub 2019 Feb 5.

Department of Veterinary Medicine, Faculty of Applied Biological Sciences, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan. Electronic address:

Recent studies have indicated that T helper 17 (Th17) cells are involved in the pathogenesis of various inflammatory diseases in dogs. However, age-related changes in canine Th17 cells have not yet been investigated. In the present study, the proportion of Th17 cells was examined in the peripheral blood mononuclear cells (PBMCs) of healthy dogs at various ages: Group 1 (n = 16; less than 1 year of age), Group 2 (n = 25; 1-5 years), and Group 3 (n = 19; 6-9 years), using flow cytometry and an anti-human interleukin (IL)-17A monoclonal antibody that reacts with canine IL-17A. The proportion of circulating Th17 cells positively correlated with age. The age-related differences were observed in the proportion of Th17 cells among Group 1 (mean ± SD: 1.52 ± 1.18%), Group 2 (mean ± SD: 3.81 ± 1.94%) and Group 3 (mean ± SD: 7.49 ± 2.54%). Our results suggest that age-related changes in Th17 cells need to be considered in future research on Th17-related diseases in dogs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.vetimm.2019.02.002DOI Listing
March 2019

Evaluation of duodenal perfusion by contrast-enhanced ultrasonography in dogs with chronic inflammatory enteropathy and intestinal lymphoma.

J Vet Intern Med 2019 Mar 19;33(2):559-568. Epub 2019 Feb 19.

Laboratory of Veterinary Internal Medicine, Department of Veterinary Clinical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan.

Background: Contrast-enhanced ultrasonography (CEUS) can be used to evaluate intestinal perfusion in healthy dogs. It is helpful for diagnosing and monitoring inflammatory bowel disease in humans and could be useful for dogs with chronic intestinal diseases.

Objectives: To examine duodenal perfusion in dogs with chronic inflammatory enteropathy (CIE) and intestinal lymphoma.

Animals: Client-owned dogs with CIE (n = 26) or intestinal lymphoma (n = 7) and dogs with gastrointestinal signs but histopathologically normal duodenum (controls, n = 14).

Methods: In this cross-sectional study, dogs with CIE were classified into remission (n = 16) and symptomatic (n = 10) groups based on clinical scores determined at the time of CEUS. The duodenum was scanned after IV injection of Sonazoid® (0.01 mL/kg). CEUS-derived perfusion parameters, including time-to-peak, peak intensity (PI), area under the curve (AUC), and wash-in and wash-out rates were evaluated.

Results: The PI was significantly higher in the symptomatic CIE group (median (range); 105.4 (89.3-128.8) MPV) than in the control group (89.9 (68.5-112.2) MPV). The AUC was significantly higher in the symptomatic CIE group (4847.9 (3824.3-8462.8) MPV.sec) than in the control (3448.9 (1559.5-4736.9) MPV.sec) and remission CIE (3862.3 (2094.5-6899.0) MPV.sec) groups. The PI and clinical score were positively correlated in the CIE group. No significant differences in perfusion parameters were detected between the lymphoma and CIE groups or the lymphoma and control groups.

Conclusions And Clinical Importance: The PI and AUC can detect duodenal inflammation and hence are potentially useful for excluding a diagnosis of CIE.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jvim.15432DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6430930PMC
March 2019

Corrigendum: Urinary Exosome-Derived microRNAs Reflecting the Changes in Renal Function in Cats.

Front Vet Sci 2019 28;6. Epub 2019 Jan 28.

Laboratory of Anatomy, Department of Basic Veterinary Sciences, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, Japan.

[This corrects the article DOI: 10.3389/fvets.2018.00289.].
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fvets.2019.00002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6360164PMC
January 2019

Effect of acute volume overload on echocardiographic indices of right ventricular function and dyssynchrony assessed by use of speckle tracking echocardiography in healthy dogs.

Am J Vet Res 2019 Jan;80(1):51-60

OBJECTIVE To determine the relationship between acute volume overload and echocardiographic indices of right ventricular (RV) function and dyssynchrony in healthy dogs. ANIMALS 7 healthy Beagles. PROCEDURES Right heart catheterization and echocardiography were performed in 7 healthy anesthetized Beagles at baseline and after induction of volume overload. Volume overload was induced by IV infusion of lactated Ringer solution (150 mL/kg/h for 90 minutes). Echocardiographic indices of RV function, including peak velocity of systolic tricuspid annular motion, tricuspid annulus plane systolic excursion, fractional area change, RV Tei index, RV longitudinal strain (RVLS), and systolic RV longitudinal strain rate (RVLSR), were obtained by use of speckle tracking echocardiography (STE). In addition, SD of the systolic shortening time of the right ventricle for the 6 segments (RV-SD6) was determined with STE. RESULTS Volume overload significantly increased the RV end-diastolic pressure, compared with the baseline value. Echocardiographic indices of RV function, except for septal RVLSR, were significantly enhanced by volume overload. In contrast, RV-SD6 did not change with volume overload. Although echocardiographic indices of RV function, except for septal RVLSR, were correlated with RV end-diastolic pressure, RV-SD6 was not correlated. CONCLUSIONS AND CLINICAL RELEVANCE Echocardiographic indices of RV function, including RVLS and RVLSR, were affected by acute short-term volume overload. Therefore, results for assessment of RV function by use of STE in dogs with clinical conditions associated with right-sided chronic volume overload, such as tricuspid and pulmonic regurgitation, should be interpreted with caution.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2460/ajvr.80.1.51DOI Listing
January 2019

Urinary Exosome-Derived microRNAs Reflecting the Changes in Renal Function in Cats.

Front Vet Sci 2018 20;5:289. Epub 2018 Nov 20.

Laboratory of Anatomy, Department of Basic Veterinary Sciences, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, Japan.

Increased incidence of kidney disease (KD) is a common concern in human and companion animals. Cats, in particular, are highly susceptible to KD. Novel KD biomarkers would help to address these problems. Therefore, we are focusing on microRNA, a highly conserved nucleic acid, as a KD biomarker for various animals. We previously reported that altered levels of urinary exosome (UExo)-derived microRNAs indicate renal pathologies in dogs. This study comprehensively examined UExo-derived microRNAs, which reflected the KD status in cats. The examined cats were divided into two groups: normal renal function (NR) and KD. Based on our previous data in dogs and cats, as well as the present data on UExo-derived microRNAs in cats by next-generation sequencing, let-7b, let-7f, miR-10a, miR-10b, miR-21a, miR-22, miR-26a, miR-27b, miR-146a, miR-181a, miR-191, and miR-486a were identified as biomarker candidates. In summary, the levels of UExo-derived let-7b, miR-22, and miR-26a significantly decreased in cats with KD from the early stages of the disease. UExo-derived miRNA levels normalized to urinary creatinine or total RNA of miR-21a was significantly higher in the KD group. Importantly, the ratio of UExo-derived miR-21a to let-7b showed a significant and strongest correlation with serum creatinine (ρ = 0.751), blood urea nitrogen (ρ = 0.754), and urinary creatinine (ρ = -0.421) among all examined indices. Further, the ratio of miR-181a to let-7b or miR-10b significantly correlated with the progression of renal dysfunction in the KD group. Thus, we identified that UExo-derived microRNAs in cats, and their raw and normalized levels could indicate altered renal function.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fvets.2018.00289DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6262179PMC
November 2018