Publications by authors named "Takahiro Maeda"

294 Publications

Type I interferon mediated induction of somatostatin leads to suppression of ghrelin and appetite thereby promoting viral immunity in mice.

Brain Behav Immun 2021 Apr 22. Epub 2021 Apr 22.

Institute for Immunology, Faculty of Medicine, LMU Munich, Germany. Electronic address:

Loss of appetite (anorexia) is a typical behavioral response to infectious diseases that often reduces body weight. Also, anorexia can be observed in cancer and trauma patients, causing poor quality of life and reduced prospects of positive therapeutic outcomes. Although anorexia is an acute symptom, its initiation and endocrine regulation during antiviral immune responses are poorly understood. During viral infections, plasmacytoid dendritic cells (pDCs) produce abundant type I interferon (IFN-I) to initiate first-line defense mechanisms. Here, by targeted ablation of pDCs and various in vitro and in vivo mouse models of viral infection and inflammation, we identified that IFN-I is a significant driver of somatostatin (SST). Consequently, SST suppressed the hunger hormone ghrelin that led to severe metabolic changes, anorexia, and rapid bodyweight loss. Furthermore, during vaccination with Modified Vaccinia Ankara virus (MVA), the SST-mediated suppression of ghrelin was critical to viral immune response, as ghrelin restrained the production of early cytokines by natural killer (NK) cells and pDCs, and impaired the clonal expansion of CD8 T cells. Thus, the hormonal modulation of ghrelin through SST and the cytokine IFN-I is fundamental for optimal antiviral immunity, which comes at the expense of calorie intake.
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http://dx.doi.org/10.1016/j.bbi.2021.04.018DOI Listing
April 2021

Title: Gene transfer by pyro-drive jet injector is a novel therapeutic approach for muscle diseases.

Gene 2021 Apr 20;788:145664. Epub 2021 Apr 20.

Laboratory of Clinical Science and Biomedicine, Graduate School of Pharmaceutical Sciences, Osaka University, Japan; Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives (OTRI), Osaka University, Japan; Laboratory of Clinical Pharmacology and Therapeutics, Graduate School of Pharmaceutical Sciences, Osaka University, Japan. Electronic address:

The angiogenic gene therapy is an attractive approach for the treatment of ischemic muscle diseases, including peripheral arterial disease and ischemic heart diseases. Although a variety of gene transfer methods have been developed, the efficiency of gene transfer is still limited. We have been developing the needleless high-energy bioinjector device, Pyro-drive Jet Injector (PJI), based on pyrotechnics using a combination of ignition powder and gunpowder, however, the utility of PJI in gene transfer into muscle tissues remains unclear. pcDNA3.1 plasmid containing Flag was injected to the thigh muscles of C57BL/6J mice using PJI or needle, as a control. Histological analysis demonstrated that the protein expression of Flag was observed in a wider range in PJI group than in needle group. To assess the validity of PJI for gene therapy, pcDNA3.1-human fibroblast growth factor 2 (FGF2), which has angiogenic activity and tissue protective properties, was injected into the ischemic thigh muscles with PJI or needle. ELISA assay revealed that the protein expression of FGF2 was increased in the thigh muscle tissues by PJI-mediated gene delivery. Significantly, histological analyses revealed that muscle fiber cross-sectional area and the number of endothelial marker CD31 (+) cells was increased in ischemic hind-limb tissues of the PJI-FGF2 group but not in those of needle-FGF2 group. To expand the applicability of the PJI-mediated gene transfer, pcDNA3.1-venus plasmid was injected into murine hearts with PJI or needle. PJI method was successful in gene transfer into murine hearts, especially into cardiomyocytes, with high efficiency when compared to needle method. Collectively, the non-needle, non-liposomal and non-viral gene transfer by PJI could be a novel therapeutic approach for muscle diseases.
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http://dx.doi.org/10.1016/j.gene.2021.145664DOI Listing
April 2021

Clinical features and chromosomal/genetic aberration in adult acute lymphoblastic leukemia in Japan: results of Fukuoka Blood & Marrow Transplant Group Studies ALL MRD 2002 and 2008.

Int J Hematol 2021 Mar 16. Epub 2021 Mar 16.

Division of Hematology and Oncology, Department of Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume, 830-0011, Japan.

Acute lymphoblastic leukemia (ALL) is a common neoplasm in children, but less frequent in adults. Since information on clinical features and genetics of adult ALL in Japan is limited, we analyzed 215 subjects aged 16-65 years with untreated ALL enrolled in the Fukuoka Blood & Marrow Transplant Group studies ALL MRD 2002 and 2008. The prevalence of ALL was bimodal, with the larger group aged 56-65 years. Immunophenotypic characterization showed B-lineage is more frequent than T-lineage ALL (78.6 vs 13.0%), with age-related differences. The proportion with BCR-ABL1 rearrangement increased progressively with age, up to 55.7% among subjects aged over 56-65 years. Rearrangements involving the KMT2A gene, ETV6-RUNX1, and TCF3-PBX1 were rare in this study cohort. The overall incidence of hyperdiploidy was only 1.7%, and there were no cases with hypodiploidy. Overall survival varied by age and cytogenetics. Older subjects and those with BCR-ABL1 tended to have inferior outcomes. In this epidemiological study of Japanese adult ALL, the majority of subjects had B-lineage ALL, the T-cell phenotype was most frequent in those aged 16-25, and BCR-ABL1 rearrangement was very common, with prevalence increasing with age. These types of adult ALL are potentially manageable with targeted therapies.
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http://dx.doi.org/10.1007/s12185-021-03116-8DOI Listing
March 2021

The impact of FGF19/FGFR4 signaling inhibition in antitumor activity of multi-kinase inhibitors in hepatocellular carcinoma.

Sci Rep 2021 Mar 5;11(1):5303. Epub 2021 Mar 5.

Division of Stem Cell and Molecular Medicine, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan.

FGF19/FGFR4 autocrine signaling is one of the main targets for multi-kinase inhibitors (MKIs). However, the molecular mechanisms underlying FGF19/FGFR4 signaling in the antitumor effects to MKIs in hepatocellular carcinoma (HCC) remain unclear. In this study, the impact of FGFR4/ERK signaling inhibition on HCC following MKI treatment was analyzed in vitro and in vivo assays. Serum FGF19 in HCC patients treated using MKIs, such as sorafenib (n = 173) and lenvatinib (n = 40), was measured by enzyme-linked immunosorbent assay. Lenvatinib strongly inhibited the phosphorylation of FRS2 and ERK, the downstream signaling molecules of FGFR4, compared with sorafenib and regorafenib. Additional use of a selective FGFR4 inhibitor with sorafenib further suppressed FGFR4/ERK signaling and synergistically inhibited HCC cell growth in culture and xenograft subcutaneous tumors. Although serum FGF19 (n = 68) patients treated using sorafenib exhibited a significantly shorter progression-free survival and overall survival than FGF19 (n = 105) patients, there were no significant differences between FGF19 (n = 21) and FGF19 (n = 19) patients treated using lenvatinib. In conclusion, robust inhibition of FGF19/FGFR4 is of importance for the exertion of antitumor effects of MKIs. Serum FGF19 levels may function as a predictive marker for drug response and survival in HCC patients treated using sorafenib.
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http://dx.doi.org/10.1038/s41598-021-84117-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7935880PMC
March 2021

Intracellular invasion ability of Streptococcus agalactiae among non-invasive isolates from human adults and companion animals in Japan.

J Infect Chemother 2021 Mar 2. Epub 2021 Mar 2.

Laboratory of Infectious Diseases, Graduate School of Infection Control Sciences & Ōmura Satoshi Memorial Institute, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8641, Japan.

Objective: This study evaluated the cell invasion ability (CIA) of Streptococcus agalactiae isolates from humans and companion animals and clarified the relationship between CIA populations and their microbiological features.

Methods: Human-origin and companion animal-origin isolates were collected along with host information. We measured CIA using human-lineage colon cancer epithelium (Caco-2) and keratinocyte (HaCaT) cell lines, via virulence-associated gene profiling (bca-rib-bac-lmb-cylE-hylB-pavA-pilB-spb1-srtC1-brpA), capsular genotyping, multilocus sequence typing, and antimicrobial resistance (AMR) phenotyping/genotyping. Significant differences in data regarding CIA into epithelium and keratinocytes and those of isolates from different hosts were assessed. We analyzed the association of CIA populations with the virulence genotypes, capsular genotypes, sequence types/clonal complexes, and AMR phenotypes/genotypes.

Results: A comparative analysis was performed between human (n = 15) and canine (n = 17) non-invasive isolates. There was a difference in CIA data between Caco-2 and HaCaT cells using human and animal isolates. For percent invasion ability into Caco-2 cells, we designated values ≥ 0.1 as high-frequency CIA and values < 0.1 as low-frequency CIA. Fourteen isolates harbored high-frequency and 18 isolates harbored low-frequency strains. There was no association between the high-frequency population and the virulence genotypes, capsular genotypes, sequence types/clonal complexes, and AMR phenotypes/genotypes.

Conclusion: This is the first report assessing the invasion ability of S. agalactiae into HaCaT and Caco-2 cells. Our observations suggest that S. agalactiae is more capable of entering Caco-2 rather than HaCaT.
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http://dx.doi.org/10.1016/j.jiac.2021.02.017DOI Listing
March 2021

The Relationship between Dental Findings and Tongue Pressure: A Survey of 745 Community-Dwelling Adults and Elderly Persons in Japan.

Gerontology 2021 Feb 17:1-8. Epub 2021 Feb 17.

Department of Oral Health, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.

Introduction: Reduced tongue pressure is one of the causes of dysphagia. The purpose of this study was to investigate the relationship between dental findings and tongue pressure, and whether prosthetic treatment prevents reduced tongue pressure.

Methods: This was a cross-sectional study. Participants were 745 community-dwelling adults and elderly persons in the Goto Islands in Nagasaki, who underwent a health checkup for residents in 2015 and 2016. Data were collected on gender; age; grip strength; hemoglobin; Creatinine (Cr); glycated hemoglobin (HbA1c); history of stroke; smoking, drinking, exercise, and walking habits; number of teeth; wearing of removable dentures; functional units of natural teeth (n-FTUs), fixed prostheses (nif-FTUs), and removable dentures (t-FTUs); and tongue pressure. The associations between each variable and tongue pressure were examined using multiple regression analysis. Next, those with 3 or fewer n-FTUs were selected, and differences in tongue pressure were compared between those with 3 or fewer nif-FTUs and those with 4 or more nif-FTUs, using a propensity score matching method.

Results: Male gender, weak grip strength, low HbA1c, no drinking, and a low number of teeth were independent factors significantly associated with lower tongue pressure. Among participants with 3 or fewer n-FTUs, the 43 with 4 or more nif-FTUs showed significantly higher tongue pressure than the 43 with 3 or fewer nif-FTUs after propensity score matching, although the number of t-FTUs was not associated with tongue pressure.

Discussion/conclusion: Tooth loss was significantly associated with lower tongue pressure. It was suggested that fixed prosthesis treatment might prevent the reduction of tongue pressure, but removable dentures did not have such an effect.
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http://dx.doi.org/10.1159/000513599DOI Listing
February 2021

Propofol midazolam for sedation during radiofrequency ablation in patients with hepatocellular carcinoma.

JGH Open 2021 Feb 22;5(2):273-279. Epub 2020 Dec 22.

Departmetn of Anesthesiology, Graduate School of Medicine Chiba University Chiba Japan.

Background And Aim: Standardization of the sedation protocol during radiofrequency ablation (RFA) in patients with hepatocellular carcinoma (HCC) is needed. This randomized, single-blind, investigator-initiated trial compared clinical outcomes during and after RFA using propofol and midazolam, respectively, in patients with HCC.

Methods: Few- and small-nodule HCC patients (≤3 nodules and ≤3 cm) were randomly assigned to either propofol or midazolam. Patient satisfaction was assessed using a 100-mm visual analog scale (VAS) (1 mm = not at all satisfied, 100 mm = completely satisfied). Sedation recovery rates 1, 2, 3, and 4 h after RFA were evaluated based on Modified Observer's Assessment of Alertness/Sedation (MOAA/S) scores; full recovery was defined as a MOAA/S score of 5.

Results: Between July 2013 and September 2017, 143 patients with HCC were enrolled, and 135 patients were randomly assigned to the treatment group. Compared with midazolam, propofol exhibited similar median procedural satisfaction (propofol: 73.1 mm, midazolam: 76.9 mm, = 0.574). Recovery rates 1 and 2 h after RFA were higher in the propofol group than in the midazolam group. Meanwhile, recovery rates observed 3 and 4 h after RFA were similar in the two groups. The safety profiles during and after RFA were almost identical in the two groups.

Conclusion: Patient satisfaction was almost identical in patients receiving propofol and midazolam sedation during RFA. Propofol sedation resulted in reduced recovery time compared with midazolam sedation in patients with HCC. The safety profiles of both propofol and midazolam sedation during and after RFA were acceptable.
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http://dx.doi.org/10.1002/jgh3.12483DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7857294PMC
February 2021

Influence of height on endothelial maintenance activity: a narrative review.

Environ Health Prev Med 2021 Feb 6;26(1):19. Epub 2021 Feb 6.

Department of General Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.

Recent studies have revealed an inverse association between height and cardiovascular disease. However, the background mechanism of this association has not yet been clarified. Height has also been reported to be positively associated with cancer. Therefore, well-known cardiovascular risk factors, such as increased oxidative stress and chronic inflammation, are not the best explanations for this inverse association because these risk factors are also related to cancer. However, impaired blood flow is the main pathological problem in cardiovascular disease, while glowing feeding vessels (angiogenesis) are the main characteristic of cancer pathologies. Therefore, endothelial maintenance activity, especially for the productivity of hematopoietic stem cells such as CD34-positive cells, could be associated with the height of an individual because this cell contributes not only to the progression of atherosclerosis but also to the development of angiogenesis. In addition, recent studies have also revealed a close connection between bone marrow activity and endothelial maintenance; bone marrow-derived hematopoietic stem cells contribute towards endothelial maintenance. Since the absolute volume of bone marrow is positively associated with height, height could influence endothelial maintenance activity. Based on these hypotheses, we performed several studies. The aim of this review is not only to discuss the association between height and bone marrow activity, but also to describe the potential mechanism underlying endothelial maintenance. In addition, this review also aims to explain some of the reasons that implicate hypertension as a major risk factor for stroke among the Japanese population. The review also aims to clarify the anthropological reasons behind the high risk of atherosclerosis progression in Japanese individuals with acquired genetic characteristics.
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http://dx.doi.org/10.1186/s12199-021-00941-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7866474PMC
February 2021

Contribution of VEGF polymorphism rs3025020 to short stature and hypertension in elderly Japanese individuals: a cross-sectional study.

J Physiol Anthropol 2021 Feb 4;40(1). Epub 2021 Feb 4.

Department of General Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.

Background: Recently, short stature has been revealed to be positively associated with hypertension, possibly because this indicates lower activity of vascular maintenance, such as angiogenesis. Vascular endothelial growth factor (VEGF) polymorphism (rs3025020) plays an important role in the progression of angiogenesis and may be associated with both hypertension and hypertension-associated short stature.

Methods: A cross-sectional study of 1377 elderly Japanese individuals aged 60-89 years was conducted. Short stature was defined as the lowest tertile of height (< 160.8 cm for men and < 148.7 cm for women). Hypertension was defined as systolic blood pressure ≥ 140 mmHg and/or diastolic blood pressure ≥ 90 mmHg and/or antihypertensive medication use.

Results: Independent of known cardiovascular risk factors, short stature was found to be positively associated with hypertension; the fully adjusted odds ratio (OR) and 95% confidence interval (CI) for hypertension were 1.51 (1.17, 1.96). With the reference group of carriers of the major allele of rs3025020, TT-homozygotes showed significantly lower OR for hypertension and short stature; the fully adjusted ORs (and 95% CIs) were 0.60 (0.41, 0.90) for hypertension and 0.59 (0.38, 0.91) for short stature, respectively.

Conclusions: Angiogenesis-related genetic factor (rs3025020) is associated with hypertension and short stature, whereas short stature is positively associated with hypertension. Further investigation is necessary in this regard; the capacity for angiogenesis might partly explain the mechanism underlying the inverse association between height and hypertension.
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http://dx.doi.org/10.1186/s40101-021-00253-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7863239PMC
February 2021

Possible mechanisms underlying the association between human T-cell leukemia virus type 1 (HTLV-1) and hypertension in elderly Japanese population.

Environ Health Prev Med 2021 Jan 29;26(1):17. Epub 2021 Jan 29.

Department of Community Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki-shi, Sakamoto 1-12-4, Nagasaki, 852-8523, Japan.

Background: Human T-cell leukemia virus type 1 (HTLV-1) activates inflammatory cascades by activating the NF-κB pathway. The minor allele of single nucleotide polymorphism (SNP) in breast cancer suppressor BRCA1-associated protein (BRAP), which has a common etiology with HTLV-1 infection, has been reported to be positively associated with carotid atherosclerosis, but inversely associated with hypertension. Therefore, HTLV-1 infection may be inversely associated with hypertension by activating endothelial maintenance, including atherosclerosis. To clarify these associations, a cross-sectional study was conducted using 2989 Japanese individuals aged 60-99 years participating in a general health check-up.

Methods: Logistic regression models were used to clarify the association between HTLV-1 and hypertension. Platelet levels stratified analyses were also performed since platelet production, which plays a crucial role in endothelium maintenance, can be stimulated by activating the NF-κB pathway.

Results: HTLV-1 infection was found to be significantly inversely associated with hypertension, particularly in subjects with high platelet levels (≥ second tertiles of platelet levels); the fully adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were 0.75 (0.62, 0.92) for total and 0.64 (0.50, 0.82) for high platelet levels, respectively. Further analysis of the non-hypertensive subjects demonstrated that HTLV-1 infection was significantly positively associated with atherosclerosis in subjects with the highest tertile of platelet levels (2.11 [1.15, 3.86]) but not in subjects with low platelet levels (first and second tertiles of platelet level) (0.89 [0.57, 1.39]).

Conclusion: Asymptomatic HTLV-1 infection is inversely associated with hypertension, possibly by activating endothelial maintenance, including atherosclerosis progression.
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http://dx.doi.org/10.1186/s12199-021-00938-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7846982PMC
January 2021

Zdhhc2 Is Essential for Plasmacytoid Dendritic Cells Mediated Inflammatory Response in Psoriasis.

Front Immunol 2020 8;11:607442. Epub 2021 Jan 8.

Laboratory of Mouse Genetics, Institute of Psychiatry and Neuroscience, Xinxiang Medical University, Henan, China.

Zdhhc family genes are composed of 24 members that regulate palmitoylation, a post-translational modification process for proteins. Mutations in genes that alter palmitoylation or de-palmitoylation could result in neurodegenerative diseases and inflammatory disorders. In this study, we found that Zdhhc2 was robustly induced in psoriatic skin and loss of Zdhhc2 in mice by CRISPR/Cas9 dramatically inhibited pathology of the ear skin following imiquimod treatment. As psoriasis is an inflammatory disorder, we analyzed tissue infiltrating immune cells and cytokine production. Strikingly we found that a master psoriatic cytokine interferon-α (IFN-α) in the lesioned skin of wildtype (WT) mice was 23-fold higher than that in Zdhhc2 deficient counterparts. In addition, we found that CD45 white blood cells (WBC) infiltrating in the skin of Zdhhc2 deficient mice were also significantly reduced. Amelioration in psoriasis and dramatically reduced inflammation of Zdhhc2 deficient mice led us to analyze the cellular components that were affected by loss of Zdhhc2. We found that imiquimod induced plasmacytoid dendritic cell (pDC) accumulation in psoriatic skin, spleen, and draining lymph nodes (DLN) were drastically decreased in Zdhhc2 deficient mice, and the expression of pDC activation marker CD80 also exhibited significantly inhibited in psoriatic skin. In further experiments, we confirmed the cell intrinsic effect of Zdhhc2 on pDCs as we found that loss of zDHHC2 in human CAL-1 pDC dampened both interferon regulatory factor 7 (IRF7) phosphorylation and IFN-α production. Therefore, we identified novel function of Zdhhc2 in controlling inflammatory response in psoriasis in mice and we also confirmed that crucial role of Zdhhc2 in pDCs by regulating IRF7 activity and production of the critical cytokine. Our results finding the dependence of IFN-α production on Zdhhc2 in inflamed murine skin and in human pDCs provide rationale for targeting this new molecule in treatment of inflammation.
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http://dx.doi.org/10.3389/fimmu.2020.607442DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7819861PMC
January 2021

Association between serum sodium level within normal range and handgrip strength in relation to hypertension status: a cross-sectional study.

Sci Rep 2021 Jan 13;11(1):1088. Epub 2021 Jan 13.

Department of Community Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki-shi, Sakamoto 1-12-4, Nagasaki, 852-8523, Japan.

Serum sodium concentration within the normal range could act as an indicator of age-related changes such as decrease in muscle strength and impairment of capillary function. Since endothelial injury stimulates endothelial repair by enhancing CD34-positive cell production, the level of serum sodium may be inversely associated with that of circulating CD34-positive cells, thus indicating the degree of age-related endothelial injury. We conducted a cross-sectional study of 246 elderly Japanese men aged 60-69 years. Subjects were stratified by hypertension status because hypertension should act as a strong confounding factor for the analyses performed in this study. Serum sodium concentration was positively associated with handgrip strength in non-hypertensive subjects [standardized parameter estimate (β) = 0.29; p = 0.003], but not for hypertensive subjects (β = 0.01; p = 0.878), while it was inversely associated with circulating CD34-positive cell levels in non-hypertensive subjects [simple correlation coefficient (r) = - 0.28; p = 0.002] but not for hypertensive subjects (r = - 0.07; p = 0.454). For non-hypertensive elderly subjects, serum sodium concentration within the normal range is positively associated with handgrip strength and inversely associated with CD34-positive cells, thus partly indicating the degree of age-related endothelium injury. These associations could prove to be an efficient tool for clarifying the background mechanism governing the decrease in age-related muscle strength.
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http://dx.doi.org/10.1038/s41598-020-80163-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7806731PMC
January 2021

Comparison between Invasive and Non-invasive Streptococcus agalactiae Isolates from Human Adults, Based on Virulence Gene Profile, Capsular Genotype, Sequence Type, and Antimicrobial Resistance Pattern.

Jpn J Infect Dis 2020 Dec 25. Epub 2020 Dec 25.

Laboratory of Infectious Diseases, Graduate School of Infection Control Sciences & Ōmura Satoshi Memorial Institute, Kitasato University, Japan.

This study assessed whether invasive group B Streptococcus (GBS) isolates were similar to non-invasive isolates from adult patients. Invasive and non-invasive GBS isolates were collected from three hospitals and two laboratory centers from January 2015 to October 2019. The isolates were identified through 16S rRNA amplicon sequencing and amplification of GBS-specific dltS. The virulence gene profile, capsular genotype, sequence type (ST)/clonal complex (CC), and antimicrobial resistance (AMR) phenotype/genotype were determined, and the 72 invasive isolates and 50 non-invasive isolates were comparatively analyzed. We observed a significantly decreased rate of rib detection in the invasive isolates compared to that in the non-invasive isolates (77.8% vs. 92.0%, p < 0.05). Additionally, we found significant differences in the prevalence of CC1 (23.6% vs. 46.0%, p < 0.05) and CC26 (12.5% vs. 2.0%, p < 0.05) between the invasive and non-invasive populations. However, there were no significant differences in the comparative data of the virulence gene profiles, capsular genotypes, other STs/CCs, and AMR phenotypes/genotypes between the two populations. These findings suggest that the invasive and non-invasive isolates shared similar features in terms of virulence gene profile, capsular genotype, ST/CC, and AMR genotype/phenotype (except for the rates of rib detection and CC1/CC26 prevalence).
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http://dx.doi.org/10.7883/yoken.JJID.2020.761DOI Listing
December 2020

The initial assessment of expert panel performance in core hospitals for cancer genomic medicine in Japan.

Int J Clin Oncol 2021 Mar 1;26(3):443-449. Epub 2021 Jan 1.

Department of Gastrointestinal Oncology, National Cancer Center Hospital East, 6-5-1, Kashiwanoha, Kashiwa-shi, Chiba, 277-8577, Japan.

Background: Since June 2019, cancer genomic profiling (CGP) tests have been reimbursed by the National Health Insurance system in Japan, with restrictions for government-designated hospitals with a molecular tumor board composed of multidisciplinary specialists, known as an expert panel (EP). The standardization of EPs is a critical challenge for implementing precision oncology in the clinical setting.

Methods: Data on consecutive cases who underwent the CGP tests at 11 core hospitals between June 2019 and January 2020 were collected. We evaluated the proportions of cases that received genomically matched treatments, including investigational new drugs (INDs) based on CGP results, and/or for which genetic counseling was recommended. Two simulated cases were annotated by each EP. The annotated reports were then centrally assessed.

Results: Each EP mainly discussed the applicability to genomically matched treatments and the necessity of performing genetic counseling. A pre-review of the report by key members in each EP reportedly made the EP conference more interactive and efficient, and thereby saved time. A total of 747 cases underwent CGP tests, 28 cases (3.7%) received genomically matched treatment, and 17 cases (2.3%) were referred for genetic counseling. Annotated reports for the simulated cases varied across the EPs, particularly the number of recommended IND trials, which seemed to be associated with the actual number of participants in IND trials.

Conclusions: This investigation provides reference data for the application of precision oncology in a clinical setting. Further investigations on the standardization of clinical annotations are warranted.
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http://dx.doi.org/10.1007/s10147-020-01844-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7895780PMC
March 2021

Association between high psychological distress and poor oral health-related quality of life (OHQoL) in Japanese community-dwelling people: the Nagasaki Islands Study.

Environ Health Prev Med 2020 Dec 10;25(1):82. Epub 2020 Dec 10.

Department of Community Medicine, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki, 852-8523, Japan.

Background: We investigated the association between psychological distress and oral health status/oral health-related quality of life (OHQoL) in Japanese community-dwelling people.

Methods: We conducted a cross-sectional study using data from the Nagasaki Islands Study. A total of 1183 (455 men and 728 women) has been analyzed in this study. Psychological distress was measured using the Kessler Psychological Distress Scale (K6). Oral health status was measured by dental examination. The OHQoL was measured using the General Oral Health Assessment Index (GOHAI). We defined the total score of ≥5 points on the K6 as high psychological distress (high-K6 group).

Results: The multiple linear regression analysis to identify the GOHAI showed that gender, K6, the total number of teeth, the number of dental caries, and visiting a dental clinic within the past 6 months significantly associated with the GOHAI. Among all of these variables, high-K6 (≥ 5) was a substantial contributing factor of the GOHAI (β = - 0.23, 95% Cl - 2.31 to -1.41, p < 0.0001).

Conclusions: It is likely that the individual with high psychological distress was strongly related to poor OHQoL even in the general population.
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http://dx.doi.org/10.1186/s12199-020-00919-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7730733PMC
December 2020

Association between self-reported walking speed and calcaneal stiffness index in postmenopausal Japanese women.

BMC Geriatr 2020 11 11;20(1):466. Epub 2020 Nov 11.

Department of Public Health, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki, 852-8523, Japan.

Background: Osteoporosis and related fractures, a worldwide public health issue of growing concern, is characterized by compromised bone strength and an increased risk of fracture. Here we show an association between self-reported walking speed and bone mass among community-dwelling postmenopausal Japanese women aged 50 years and older. DESIGN; CROSS-SECTIONAL STUDY: Setting and Participants; The survey population included 1008 postmenopausal women 50-92 years of age residing in rural communities.

Methods: Self-reported walking speed was ascertained by asking the participants: "Is your walking speed faster than others of the same age and sex?" to which participants responded "yes (faster)" or "no (moderate/slower)." Calcaneal stiffness index was measured.

Results: Women with a faster self-reported walking speed were younger and had a lower BMI, higher stiffness index, and higher grip strength than women with a slower walking speed. Multiple linear regression analysis adjusted for age, BMI, grip strength, comorbidity, current smoking, and alcohol drinking status showed a significant association between faster self-reported walking speed and higher calcaneal stiffness index (p <  0.001).

Conclusions: Our findings suggest that questionnaires of walking speed may be useful for predicting bone mass and that a fast self-reported walking may benefit bone health in postmenopausal women.
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http://dx.doi.org/10.1186/s12877-020-01858-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7661156PMC
November 2020

The linkage between medical student readiness for interprofessional learning and interest in community medicine.

Int J Med Educ 2020 Nov 6;11:240-244. Epub 2020 Nov 6.

Center for Comprehensive Community Care Education, Nagasaki University Graduate School of Biomedical Sciences.

Objectives: The purpose of this study is to investigate the relationship between medical student readiness for interprofessional learning and interest in community medicine prior to incorporating community-oriented interprofessional education into the curriculum.

Methods: A questionnaire was administered to students at Nagasaki University School of Medicine in Japan during each of three consecutive years (N=2244). The Readiness for Interprofessional Learning Scale (RIPLS) was administered in addition to a questionnaire to evaluate interest in community medicine. The Kruskal-Wallis and Steel-Dwass tests were used to determine differences between school years. Correlation between the RIPLS score and interest in community medicine was evaluated with Spearman's rank correlation coefficient. Relationships between RIPLS score and demographic parameters, and interest in community medicine were evaluated with multiple linear regression analysis.

Results: Eighty-four percent (1891/2244) of students responded. The RIPLS score was highest in school year 1, followed by year 6, year 5, year 3, and years 4 and 2. Interest in community medicine correlated with the RIPLS score (r = 0.332, p < 0.001), but less in year 1 (r = 0.125, p = 0.002) than in other years. RIPLS score was significantly associated with gender, age, school year, interest in community medicine, but not the year that the survey was conducted.

Conclusions: Community-oriented interprofessional education has the potential to improve attitudes towards interprofessional learning. When introducing this promising education into the curriculum from year 1, attracting students' interest in community medicine should be considered.
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http://dx.doi.org/10.5116/ijme.5f89.83aeDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7883804PMC
November 2020

Associations between thyroid-stimulating hormone and hypertension according to thyroid cyst status in the general population: a cross-sectional study.

Environ Health Prev Med 2020 Nov 5;25(1):69. Epub 2020 Nov 5.

Division of Promotion of Collaborative Research on Radiation and Environment Health Effects, Atomic Bomb Disease Institute, Nagasaki University, Nagasaki, Japan.

Background: The absence of thyroid cysts may indicate latent thyroid damage, as demonstrated in our previous study. However, the association between the absence of thyroid cysts and latent functional damage of the thyroid is unknown. At low thyroid hormone productivity, which may be associated with latent functional damage of the thyroid, the association between thyroid-stimulating hormone (TSH) and hypertension might be enhanced. Therefore, we evaluated the association between TSH level and hypertension stratified by thyroid cyst status.

Methods: We conducted a cross-sectional study of 1724 euthyroid Japanese individuals aged 40-74 years who participated in an annual health checkup in 2014.

Results: In the study population, 564 and 686 participants had thyroid cysts and hypertension, respectively. A significant positive association was observed between TSH and hypertension in subjects without a thyroid cyst but not in subjects with thyroid cysts. There was a significant positive association between hypertension and TSH in subjects without a thyroid cyst (odds ratio [OR] 1.27; 95% confidence intervals [CI] 1.01, 1.61) but not in subjects with thyroid cysts (OR 0.79; CI 0.57, 1.09) in the model fully adjusted for known confounding factors. The correlation between the TSH and free triiodothyronine (fee T3) levels (simple correlation coefficient [r] = - 0.13, p < 0.01) was stronger in the subjects without thyroid cysts than in those with thyroid cysts (r = - 0.03, p = 0.525).

Conclusions: TSH is positively associated with hypertension only in individuals without thyroid cysts. The correlation between the TSH and free T3 levels was stronger in the subjects without thyroid cysts than in those with thyroid cysts. Therefore, the absence of thyroid cysts could be related to the association between TSH level and hypertension, possibly by indicating that the subjects without thyroid cysts had limited thyroid hormone reserves. Therefore, the absence of thyroid cysts could indicate the latent functional damage of the thyroid.
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http://dx.doi.org/10.1186/s12199-020-00910-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7646082PMC
November 2020

Outcome predictors after retransplantation in relapsed acute lymphoblastic leukemia: a multicenter, retrospective study.

Ann Hematol 2021 Jan 5;100(1):197-208. Epub 2020 Nov 5.

Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Science, 3-1-1, Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.

Retransplantation is the only curative treatment option for patients with acute lymphoblastic leukemia (ALL) that has relapsed after allogeneic hematopoietic cell transplantation (allo-HCT); however, data in this setting remain scant. Hence, this multicenter, retrospective study aims to determine outcome predictors after retransplantation in relapsed ALL. We examined 55 recipients who underwent multiple allo-HCTs during 2006-2018. The 2-year overall survival (OS), progression-free survival (PFS), and non-relapse mortality rates were 35.9%, 29.1%, and 23.6%, respectively. We observed a trend of better outcome in Ph + ALL (n = 22) patients compared with non-Ph ALL (n = 33) patients; the 2-year PFS was 40.9% versus 21.2%, indicating a beneficial effect of more potent second- or third-generation tyrosine kinase inhibitors. Univariate analysis revealed that late relapse after the previous transplant was the only significant predictor of better transplant outcome among Ph + ALL patients, whereas factors related to prolonged OS/PFS in non-Ph ALL patients were late relapse after the previous transplant, longer duration from disease relapse/progression to second or more allo-HCT, disease status at the transplantation, and good performance status. Nevertheless, further investigations are warranted to determine whether novel molecular-targeted agents with higher efficacy and fewer toxicities could exceed conventional chemotherapies as a bridging strategy to next allo-HCT and improve the outcomes of non-Ph ALL patients.
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http://dx.doi.org/10.1007/s00277-020-04310-0DOI Listing
January 2021

Hand-assisted laparoscopic ileal ureter substitution for ureteral obstruction after right ureteral rupture: A case report.

Urol Case Rep 2020 Nov 24;33:101326. Epub 2020 Jun 24.

Department of Urology, Kawasaki Municipal Hospital, 12-1 Shinkawadori, Kawasaki-ku, Kawasaki-city, Kanagawa, 210-0013, Japan.

Iatrogenic ureteral rupture is a serious complication. In the past, ileal ureter substitution was performed with open, laparoscopic, and robot-assisted procedure; however, there are problems with operation invasiveness and difficulty. We present a 72-year-old female whose ureter was completely injured at the ureteropelvic junction and torn longitudinally in full length at the time of transurethral lithotripsy. Although initially she had nephrostomy, we were able to internalize with hand-assisted laparoscopic ileal ureter substitution for obstruction over the full length of the ureter.
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http://dx.doi.org/10.1016/j.eucr.2020.101326DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7573837PMC
November 2020

Midterm Outcomes of Autologous Osteochondral Graft Transplantation Only in the Femoral Condyle without Treating the Tibial Plateau with Subchondral Bone Exposed.

Cartilage 2020 Oct 23:1947603520967066. Epub 2020 Oct 23.

Department of Orthopaedic Surgery, National Hospital Organization Kyoto Medical Center, Kyoto, Japan.

Objective: This study aimed to examine the midterm clinical outcomes of autologous osteochondral grafts (AOG) that were performed in the femoral condyle without treating the tibial plateau with subchondral bone exposed, and to compare these outcomes with those of AOG used in patients with osteoarthritis (lateral type or medial type) or osteonecrosis.

Design: The study included 6 men and 16 women and 11 right knees and 11 left knees. The mean operative age was 56.0 years (range, 21-76 years), and the mean follow-up period was 98.4 months (range, 60-164 months). Six patients had lateral type osteoarthritis (OAL), 7 had medial type osteoarthritis (OAM), and 9 had osteonecrosis (ON). The patients' knee symptoms as their clinical outcome were evaluated using the knee scoring system of the Japanese Orthopedic Association (JOA), and the International Knee Documentation Committee (IKDC) subjective score.

Results: The postoperative clinical outcomes of the OAL and ON group were significantly better than their preoperative clinical scores and remained the same until the final follow-up. However, the clinical outcomes of OAM improved 2 years after AOG, but eventually decreased thereafter. The number of worse cases in the OAM group was significantly larger than those in the OAL and ON groups.

Conclusion: In these procedures, the postoperative clinical outcomes of the OAL and ON groups were significantly better than their preoperative clinical scores and were maintained for about 8 years. However, the clinical outcomes of OAM improved until 2 years after AOG, but eventually decreased thereafter.
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http://dx.doi.org/10.1177/1947603520967066DOI Listing
October 2020

Analyses of Intermediate-Stage Hepatocellular Carcinoma Patients Receiving Transarterial Chemoembolization prior to Designing Clinical Trials.

Liver Cancer 2020 Sep 22;9(5):596-612. Epub 2020 Jul 22.

Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan.

Background: Intermediate-stage hepatocellular carcinoma (HCC) has a high frequency of recurrence and progression to advanced stage after transarterial chemoembolization (TACE), particularly in patients with high tumor burden. Promising new results from immune checkpoint inhibitors (ICIs) and ICI-based therapies are expected to replace TACE, especially in HCC patients with high tumor burden.

Aims: The present study aimed to evaluate the effectiveness of TACE with a view to design clinical trials comparing TACE and ICIs.

Methods: We retrospectively identified intermediate-stage HCC patients undergoing TACE from our database and subdivided patients into low- and high-burden groups based on three subclassification models using the diameter of the maximum tumor and the number of tumors. Clinical outcomes were compared between low- and high-burden intermediate-stage HCC.

Results: Of 1,161 newly diagnosed HCC patients, 316 were diagnosed with intermediate-stage disease and underwent TACE. The median overall survival from high-burden intermediate-stage disease was not significantly different by clinical course, reaching high tumor burden in all subclassification models. The prognosis of high-burden patients after initial TACE was poor compared with low-burden patients for two models (except for the up-to-seven criteria). In all three models, high-burden patients showed a poor durable response rate (DRR) both ≥3 months and ≥6 months and poor prognosis after TACE. Moreover, patients with confirmed durable response ≥3 months and ≥6 months showed better survival outcomes for high-burden intermediate-stage HCC.

Conclusions: Our results demonstrate the basis for selecting a population that would not benefit from TACE and setting DRR ≥3 months or ≥6 months as alternative endpoints when designing clinical trials comparing TACE and ICIs.
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http://dx.doi.org/10.1159/000508809DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7548915PMC
September 2020

Anti-thyroid peroxidase antibody and subclinical hypothyroidism in relation to hypertension and thyroid cysts.

PLoS One 2020 2;15(10):e0240198. Epub 2020 Oct 2.

Division of Strategic Collaborative Research, Atomic Bomb Disease Institute, Nagasaki University, Nagasaki, Japan.

Hypertension frequently occurs in subclinical hypothyroidism (SCH). By bolstering thyroid inflammation, anti-peroxidase antibody (TPO-Ab) causes autoimmune thyroiditis, which is one of the most common causes of SCH. Since the absence of thyroid cysts is associated with TPO-Ab (+) based on the indication of latent thyroid damage, we explored the potential mechanism underlying the association among TPO-Ab, SCH, hypertension, and thyroid cysts. A cross-sectional study of 1,483 Japanese aged 40-74 years was conducted. Thyroid cysts were defined as those having a maximum diameter of ≥ 2.0 mm, containing no solid component. TPO-Ab (+) was positively associated with SCH with hypertension (adjusted odds ratio [OR] and 95% confidence interval [CI], 2.62 [1.40, 4.89]) but not with SCH without hypertension (0.84 [0.37, 1.89]), respectively. Moreover, among participants without thyroid cysts, SCH was positively associated with hypertension (2.15 [1.23, 3.76]) but not among participants with thyroid cysts (0.58 [0.16, 2.16]), respectively. TPO-Ab was positively associated with SCH with hypertension, but not with SCH without hypertension. In addition, status of thyroid cysts might act as a determinant factor on the association between SCH and hypertension. These findings are efficient tools to clarify the background mechanism that underlies SCH.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0240198PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7531803PMC
December 2020

Normal range of anti-thyroid peroxidase antibody (TPO-Ab) and atherosclerosis among eu-thyroid population: A cross-sectional study.

Medicine (Baltimore) 2020 Sep;99(38):e22214

Division of Strategic Collaborative Research, Atomic Bomb Disease Institute, Nagasaki University, Nagasaki.

Anti-thyroid peroxidase antibody (TPO-Ab), which is the known cause of autoimmune thyroid disease, enhances proinflammatory cytokine responses. Since low-grade inflammation is a known risk factor for atherosclerosis, a normal range of TPO-Ab (TPO-Ab negative) could be positively associated with atherosclerosis among participants with normal thyroid function. However, no study reported the association between normal range of TPO-Ab and atherosclerosis among eu-thyroid participants. A cross-sectional study was conducted with 1165 Japanese individuals with normal thyroid function (ie, normal range of free triiodothyronine [free T3] and free thyroxine [free T4]), aged 40 to 74 years, who participated in an annual health checkup in 2014. Among the study population, 115 were diagnosed as having atherosclerosis. A normal range value of TPO-Ab titer is revealed to be positively associated with atherosclerosis; sex, age, thyroid function (free T3 and thyroid-stimulating hormone), and known cardiovascular risk factor adjusted odds ratio and 95% confidence interval of atherosclerosis for logarithmic values of TPO-Ab was 2.23 (1.11, 4.47). When we limited the analysis to participants with normal levels of thyroid-stimulating hormone, this association became slightly stronger (2.65 [1.27,5.51]). Among the eu-thyroid general population, a normal range of TPO-Ab titer is revealed to be positively associated with atherosclerosis. Even though a TPO-Ab titer is not clinically relevant and is not associated with autoimmune thyroid disease, it could influence endothelial remodeling including atherosclerosis.
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http://dx.doi.org/10.1097/MD.0000000000022214DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7505314PMC
September 2020

Beneficial tyrosine kinase inhibitor therapy in a patient with relapsed BCR-ABL1-like acute lymphoblastic leukemia with CCDC88C-PDGFRB fusion.

Int J Hematol 2021 Feb 19;113(2):285-289. Epub 2020 Sep 19.

Division of Hematology and Oncology, Department of Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume, 830-0011, Japan.

BCR-ABL1-like acute lymphoblastic leukemia (ALL) is a neoplasm of lymphoblasts committed to the B-cell lineage that lack the BCR-ABL1 translocation but show a pattern of gene expression very similar to that seen in ALL with BCR-ABL1 with poor prognosis. A 22-year-old female was diagnosed with common-B-cell-ALL positive for CD10, CD19, CD22, CD79a, CD34, HLA-DR, and TdT in January 2017, and achieved complete remission (CR) with induction therapy, followed by consolidation therapy and maintenance therapy. In March 2020, 6 months after the completion of maintenance therapy, she relapsed. Inotuzumab ozogamicin (IO) was administered, and on day 28, bone marrow evaluation showed a morphologic CR. She had an HLA-identical sibling, and transplantation in her 2nd CR was planned. Because her ALL had been identified as BCR-ABL1-like ALL with CCDC88C-PDGFRB fusion, she was treated with imatinib for 2 months accompanied by 2 intrathecal methotrexate therapies, and 1 course of L-asparaginase, vincristine, and prednisolone in an outpatient setting. MRD analysis revealed potent efficacy of 2 months imatinib therapy; IgH MRD decreased from 1 × 10 to 1 × 10, and CCDC88C-PDGFRB/10ABL from 37.3 to 0. It is earnestly desired that well-designed clinical trials of TKI in ABL class-mutant BCR-ABL1-like ALL be conducted in Japan.
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http://dx.doi.org/10.1007/s12185-020-03006-5DOI Listing
February 2021

Significance of prophylactic urethrectomy at the time of radical cystectomy for bladder cancer.

Jpn J Clin Oncol 2021 Feb;51(2):287-295

Department of Urology, Keio University School of Medicine, Tokyo, Japan.

Background: Prophylactic urethrectomy at the time of radical cystectomy is frequently recommended for patients with bladder cancer at a high risk of urethral recurrence without definitive evidence. The present study attempted to clarify the survival benefits of performing prophylactic urethrectomy.

Methods: We identified 214 male patients who were treated by radical cystectomy with an incontinent urinary diversion in our seven institutions between 2004 and 2017. We used propensity score matching and ultimately identified 114 patients, 57 of whom underwent prophylactic urethrectomy (prophylactic urethrectomy group) and 57 who did not (non-prophylactic urethrectomy group).

Results: No significant differences were observed in the 5-year overall survival rate between the prophylactic urethrectomy and non-prophylactic urethrectomy groups in the overall. However, the local recurrence rate was significantly lower in the prophylactic urethrectomy group than in the non-prophylactic urethrectomy group (P = 0.015). In the subgroup of 58 patients with multiple tumours and/or concomitant carcinoma in situ at the time of transurethral resection of bladder tumour, the 5-year overall survival rate was significantly higher in the prophylactic urethrectomy group than in the non-prophylactic urethrectomy group (P = 0.021). A multivariate analysis revealed that performing prophylactic urethrectomy was the only independent predictor of the overall survival rate (P = 0.016). In those patients who were treated without neoadjuvant chemotherapy (n = 38), the 5-year overall survival rate was significantly higher in the prophylactic urethrectomy group than in the non-prophylactic urethrectomy group (P = 0.007).

Conclusions: Prophylactic urethrectomy at the time of radical cystectomy may have a survival benefit in patients with multiple tumours and/or concomitant carcinoma in situ, particularly those who do not receive neoadjuvant chemotherapy.
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http://dx.doi.org/10.1093/jjco/hyaa168DOI Listing
February 2021

Intracellular Invasion Ability and Associated Microbiological Characteristics of Streptococcus canis in Isolates from Japan.

Jpn J Infect Dis 2021 Mar 31;74(2):129-136. Epub 2020 Aug 31.

Laboratory of Infectious Diseases, Graduate School of Infection Control Sciences & Ōmura Satoshi Memorial Institute, Kitasato University, Japan.

This study evaluated the cell invasion ability (CIA) of Streptococcus canis isolates, and clarified the relationship between high-frequency CIA and its microbiological features. Of the companion animal-origin isolates (n = 117) that were obtained in 2017, 40 isolates were randomly selected with the host information, with two human blood-origin isolates included. CIA was measured using human colon carcinoma epithelium and the hemolytic activity (HA) using sheep blood, along with S. canis M-like protein (SCM) allele typing, sequence type (ST) determination, and antimicrobial resistance (AMR) phenotyping/genotyping. CIA measurements revealed that 19 and 24 isolates had high- and low-frequencies, respectively. HA assessment revealed that 24 and 19 isolates were categorized as high- and low- level, respectively. No difference was observed in the high-/low-level HA between the high- /low-frequency CIA populations. A significant difference was found in the high-/low-frequency CIA between the SCM group I/II populations. Additionally, a significantly higher CIA was found in the SCM allele type 10/type 11 than in the others. A significant association was observed between high-frequency CIA and the ST21/ST41 populations. No difference was found in the high-/low-frequency CIA between the presence and absence of the AMR phenotype/genotype. These observations suggest a relationship between high-frequency CIA and its microbiological characteristics (SCM allele type 10/type 11 or ST21/ST41).
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http://dx.doi.org/10.7883/yoken.JJID.2020.382DOI Listing
March 2021

The Efficacy and Safety of Highly-Bioavailable Curcumin for Treating Knee Osteoarthritis: A 6-Month Open-Labeled Prospective Study.

Clin Med Insights Arthritis Musculoskelet Disord 2020 12;13:1179544120948471. Epub 2020 Aug 12.

Department of Orthopedic Surgery, National Hospital Organization, Kyoto Medical Center, Kyoto, Japan.

Background: We previously developed a surface-controlled water-dispersible form of curcumin that we called Theracurmin. The area under the blood concentration-time curve (AUC) of Theracurmin in humans was 27-fold higher than that of curcumin powder. Previously, we reported on the anti-inflammatory effects of Theracurmin for knee osteoarthritis.

Hypothesis/purpose: We determined the clinical effects of orally administered Theracurmin in patients with knee osteoarthritis over a 6-month period.

Study Design: Open prospective study.

Methods: Fifty patients Kellgren-Lawrence grade II, III, or IV knee osteoarthritis who were above 40 years old were enrolled in this clinical study. Theracurmin containing 180 mg/day of curcumin was administered orally every day for 6 months. To monitor for adverse events, blood biochemistry analyses were performed before and after 6 months of each intervention. The patients' knee symptoms were evaluated at 0, 1, 2, 3, 4, 5, and 6 months based on the Japanese Knee Osteoarthritis Measure, the knee pain visual analog scale, and the knee scoring system of the Japanese Orthopedic Association.

Results: Five cases dropped out during the study, but no cases dropped out because of major problems. No major side effects were observed with Theracurmin treatment, including the blood biochemistry analysis results. The effective group included 34 cases (75.6%), while the not-effective group included 11 cases.

Conclusion: This study demonstrates the safety and good efficacy of Theracurmin for various types of knee osteoarthritis. Theracurmin shows great potential for the treatment of human knee osteoarthritis.
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http://dx.doi.org/10.1177/1179544120948471DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7425263PMC
August 2020

Potential mechanisms underlying the association between single nucleotide polymorphism (BRAP and ALDH2) and hypertension among elderly Japanese population.

Sci Rep 2020 08 25;10(1):14148. Epub 2020 Aug 25.

Department of Community Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki-shi, Sakamoto 1-12-4, Nagasaki, 852-8523, Japan.

Minor allele frequency (MAF) of rs3782886 (BRAP) and rs671 (ALDH2) are reported to be inversely associated with blood pressure. Another study revealed that hematopoietic activity which is evaluated by reticulocytes could influenced on hypertension status partly by indicating activity of endothelial maintenance. Therefore, to evaluate the association between genetic factor and hypertension, influence of hematopoietic activity should be considered. A multi-faced analysis was performed in a simple general elderly population model (1,313 older Japanese aged 60-98 years). Participants were stratified by median values of reticulocytes (5.21 × 10 cells/μL for men and 4.65 × 10 cells/μL for women). Independent of known cardiovascular risk factors, MAF of rs3782886 and rs671 are significantly inversely associated with hypertension for participants with high hematopoietic activity (high reticulocytes level) (fully adjusted odds ratio (ORs) were 0.72 (0.55, 0.96) for rs3782886 and 0.72 (0.54, 0.96) for rs671) but not for low reticulocytes count (the corresponding values were 1.05 (0.79, 1.39) and 1.08 (0.81, 1.45), respectively). Hematopoietic activity evaluated by reticulocytes levels could influence on the association between single nucleotide polymorphism (rs3782886 and rs671) and hypertension. Those results were efficient tool to clarify the part of the mechanism that underlying the association between genetic factor and hypertension.
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http://dx.doi.org/10.1038/s41598-020-71031-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7447746PMC
August 2020