22 results on '"Akihiro Kuma"'
Search Results
2. Development of chronic kidney disease influenced by serum urate and body mass index based on young-to-middle-aged Japanese men: a propensity score-matched cohort study
- Author
-
Kazuhiko Enta, Akihiro Kuma, Kosuke Mafune, Bungo Uchino, Yoko Ochiai, and Akihiko Kato
- Subjects
Medicine - Published
- 2022
- Full Text
- View/download PDF
3. Development of chronic kidney disease influenced by serum urate and body mass index based on young-to-middle-aged Japanese men: a propensity score-matched cohort study
- Author
-
Akihiro Kuma, Kosuke Mafune, Bungo Uchino, Yoko Ochiai, Kazuhiko Enta, and Akihiko Kato
- Subjects
Adult ,Male ,General Medicine ,Middle Aged ,Body Mass Index ,Uric Acid ,Cohort Studies ,Young Adult ,Japan ,Risk Factors ,Humans ,Medicine ,Renal Insufficiency, Chronic ,Propensity Score ,Glomerular Filtration Rate ,Retrospective Studies - Abstract
ObjectiveTo investigate the association between serum uric acid (SUA) level and body mass index (BMI) on the development of chronic kidney disease (CKD) in working men aged 20–60 years.DesignRetrospective cohort study.SettingData from employees’ annual health check-ups were collected from two companies in 2009 and 2014.ParticipantsA total of 16 708 working men were recruited. We excluded participants with missing essential data (N=7801), who had basal estimated glomerular filtration rate (eGFR) 2 and/or proteinuria (N=698) or with the absence of follow-up data (N=2).Primary outcomeeGFR 2 and/or proteinuria (≥1+) in 2014 (defined as incident CKD).ResultsThe cut-off values of SUA for incident CKD were 6.6 mg/dL in both young (20–39 years old) and middle-aged (40–60 years old) men analysed by receiver operator characteristics. ORs for incident CKD were assessed on propensity score-matched (1:1) cohorts. In young participants (N=1938), after propensity score matching, a coexistence of high-level SUA (≥6.6 mg/dL) and overweight (BMI ≥25 kg/m2) was a significant risk factor of incident CKD (OR=2.18, 95% CI 1.10 to 4.31, p=0.025), but high-level SUA was not an independent risk factor without overweight status (p=0.174). In middle-aged participants (N=2944) after propensity score matching, high-level SUA was a significant risk factor of incident CKD both with or without overweight (OR=1.44, 95% CI 1.02 to 2.04, p=0.037; OR=1.32, 95% CI 1.01 to 1.73, p=0.041, respectively).ConclusionThese findings suggest that high-level SUA is strongly associated with incident CKD in overweight young adult men.
- Published
- 2022
4. Downregulation of let-7 by Electrical Acupuncture Increases Protein Synthesis in Mice
- Author
-
Faten Hassounah, Hui Cai, Ying Huang, Manshu Yu, Akihiro Kuma, Xiaonan H. Wang, Yanhua Wang, and Janet D. Klein
- Subjects
microRNA ,Physiology ,Myogenesis ,Chemistry ,Skeletal muscle ,Stimulation ,Acu/LFES ,Hindlimb ,Protein degradation ,Exosome ,Muscle atrophy ,Cell biology ,medicine.anatomical_structure ,Downregulation and upregulation ,Physiology (medical) ,mTOR ,medicine ,exosome ,QP1-981 ,skeletal muscle ,medicine.symptom ,IGF-1 signaling ,Original Research - Abstract
BackgroundOur previous study found that acupuncture with low frequency electrical stimulation (Acu/LFES) prevents muscle atrophy by attenuation of protein degradation in mice. The current study examines the impact of Acu/LFES on protein synthesis.MethodC57/BL6 mice received Acu/LFES treatment on hindlimb for 30 min once. Acu/LFES points were selected by WHO Standard Acupuncture Nomenclature and electric stimulation applied using an SDZ-II Electronic acupuncture instrument. Muscle protein synthesis was measured by the surface-sensing of translation (SUnSET) assay. Exosomes were isolated using serial centrifugation and concentration and size of the collected exosomes were measured using a NanoSight instrument. The mature microRNA library in serum exosomes was validated using a High Sensitivity DNA chip.ResultsProtein synthesis was enhanced in the both hindlimb and forelimb muscles. Blocking exosome secretion with GW4869 decreased the Acu/LFES-induced increases in protein synthesis. MicroRNA-deep sequencing demonstrated that four members of the Let-7 miRNA family were significantly decreased in serum exosomes. Real time qPCR further verified Acu/LFES-mediated decreases of let-7c-5p in serum exosomes and skeletal muscles. In cultured C2C12 myotubes, inhibition of let-7c not only increased protein synthesis, but also enhanced protein abundance of Igf1 and Igf1 receptors. Using a luciferase reporter assay, we demonstrated that let-7 directly inhibits Igf1.ConclusionAcu/LFES on hindlimb decreases let-7-5p leading to upregulation of the Igf1 signaling and increasing protein synthesis in both hindlimb and forelimb skeletal muscles. This provides a new understanding of how the electrical acupuncture treatment can positively influence muscle health.
- Published
- 2021
5. Effects of bicarbonate/lactate-buffered neutral peritoneal dialysis fluids on angiogenesis-related proteins in patients undergoing peritoneal dialysis
- Author
-
Ikutaro Furuno, Yutaka Otsuji, Masaru Araki, Yasushi Oginosawa, Kazutoshi Nakazono, Akihiro Kuma, Yuki Tsuda, Masahito Tamura, Hiromichi Ueno, Masaharu Kataoka, Hiroyuki Morimoto, Emi Hasegawa, Kenya Sanada, Yoichi Ueta, and Tetsu Miyamoto
- Subjects
Nephrology ,medicine.medical_specialty ,Biocompatibility ,Angiogenesis ,Urology ,medicine.medical_treatment ,Bicarbonate ,030232 urology & nephrology ,030204 cardiovascular system & hematology ,Pharmacology ,Peritoneal dialysis ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Internal medicine ,medicine ,In patient ,Transplantation ,Oncogene ,business.industry ,Growth-related oncogene ,Biocompatible material ,Diseases of the genitourinary system. Urology ,Bicarbonate/lactate-buffered neutral peritoneal dialysis fluid ,chemistry ,Chemokine ,RC870-923 ,business - Abstract
Background In order to facilitate the safe and long-term delivery of peritoneal dialysis (PD), it is necessary to improve the biocompatibility of peritoneal dialysis fluids (PDFs). The novel bicarbonate/lactate-buffered neutral PDFs (B/L-PDFs) are expected to be improved biocompatible. This study evaluated the biocompatibility of B/L-PDFs by analysis on the profile of angiogenesis-related proteins in drained dialysate of patients undergoing PD. Methods Concentrations of 20 angiogenesis-related proteins in the dialysate were semi-quantitatively determined using a RayBio® Human Angiogenesis Antibody Array and were compared between B/L-PDFs and conventional lactate-buffered neutral PDFs (L-PDFs). Results The expression of growth-related oncogene (GRO α/β/γ), which belongs to the CXC chemokine family, decreased significantly after use of the B/L-PDFs compared to the L-PDFs (P = 0.03). The number of the proteins with lower level in the B/L-PDFs compared with L-PDFs was significantly negatively correlated with the PD duration (Spearman ρ = − 0.81, P = 0.004). Conclusion This study suggested that B/L-PDFs are more biocompatible than conventional PDFs.
- Published
- 2021
6. Significance of kidney biopsy in autosomal dominant tubulointerstitial kidney disease-UMOD: is kidney biopsy truly nonspecific?
- Author
-
Tadashi Konoshita, Junko Imura, Hiroaki Muramoto, Michihiro Mitobe, Kiyoaki Ito, Ichiro Mizushima, Hiroaki Tsuruta, Mitsuhiro Kawano, Akira Iguchi, Shoichiro Daimon, Tamehito Onoe, Satoshi Hara, Takeshi Zoshima, Takayasu Mori, Nao Kishimoto, Akihiro Kuma, Maki Shimizu, Kazunori Yamada, and Yoshifumi Ubara
- Subjects
Adult ,Male ,0301 basic medicine ,Nephrology ,medicine.medical_specialty ,Pathology ,Tamm–Horsfall protein ,Adolescent ,Biopsy ,Tamm-Horsfall protein ,Kidney biopsy ,030232 urology & nephrology ,Autosomal dominant tubulointerstitial kidney disease ,Gene mutation ,Kidney ,lcsh:RC870-923 ,Sensitivity and Specificity ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Uromodulin ,medicine ,Humans ,biology ,medicine.diagnostic_test ,business.industry ,Glomerulosclerosis ,Middle Aged ,Polycystic Kidney, Autosomal Dominant ,lcsh:Diseases of the genitourinary system. Urology ,medicine.disease ,Kidney Tubules ,030104 developmental biology ,medicine.anatomical_structure ,Mutation ,biology.protein ,Tubulointerstitial fibrosis ,Female ,business ,Research Article ,Kidney disease - Abstract
Background Autosomal dominant tubulointerstitial kidney disease (ADTKD) is a rare hereditary disease caused by a variety of genetic mutations. Carriers of a mutation in the responsible genes are at risk of reaching end-stage kidney disease typically in middle age. The frequency of this disease is assumed to be underestimated because of a lack of disease-specific signs. Pathological findings obtained from kidney of uromodulin related ADTKD (ADTKD-UMOD) patients are regarded as non-specific and less-informative for its diagnosis. This research was undertaken to evaluate the significance of kidney biopsy in ADTKD-UMOD patients. Methods Thirteen patients from 10 families with nine identified uromodulin (UMOD) gene mutations who underwent kidney biopsy in the past were studied. Their kidney tissues were stained with anti-UMOD antibody in addition to conventional methods such as PAS staining. When positive, the numbers of tubules with visible UMOD protein accumulations were calculated based on the total numbers of UMOD expressing tubules. Pathological findings such as tubulointerstitial fibrosis, atrophy, inflammation and glomerulosclerosis were also evaluated and analyzed. Results Interstitial fibrosis and tubular atrophy were present in all 13 patients. Most atrophic tubules with thickening and lamellation of tubular basement membranes showed negative UMOD staining. In all but two patients with C94F mutations, massive accumulation of UMOD proteins was observed in the renal endoplasmic reticulum. UMOD accumulations were also detectable by PAS staining as polymorphic unstructured materials in the 11 patients at frequencies of 2.6–53.4%. 80.4% of the UMOD accumulations were surrounded by halos. The detection rate of UMOD accumulations positively correlated with eGFR. Glomerulosclerosis was detected in 11/13 patients, with a frequency of 20.0 to 61.1%, while no cystic dilatations of glomeruli were detected. Conclusions Massively accumulated UMOD proteins in ADTKD-UMOD kidneys are detectable not only by immunostaining using anti-UMOD antibody but also by conventional methods such as PAS staining, although their detection is not easy. These findings can provide important clues to the diagnosis of ADTKD-UMOD. Kidney biopsy in ADTKD-UMOD may be more informative than assumed previously.
- Published
- 2021
7. Alteration of normal level of serum urate may contribute to decrease in estimated glomerular filtration rate decline in healthy Japanese men
- Author
-
Yoko Ochiai, Kazuhiko Enta, Bungo Uchino, Akihiro Kuma, Akihiko Kato, and Kosuke Mafune
- Subjects
Adult ,Male ,medicine.medical_specialty ,Renal function ,hyperuricemia ,Kidney ,urologic and male genital diseases ,Critical Care and Intensive Care Medicine ,Japan ,Risk Factors ,Internal medicine ,Humans ,Medicine ,Hyperuricemia ,Renal Insufficiency, Chronic ,propensity score ,Retrospective Studies ,business.industry ,Serum uric acid ,food and beverages ,Normal level ,General Medicine ,medicine.disease ,Diseases of the genitourinary system. Urology ,Uric Acid ,Serum urate ,Linear relationship ,Endocrinology ,Nephrology ,occupational health ,Linear Models ,Clinical Study ,RC870-923 ,sense organs ,business ,chronic kidney disease ,Glomerular Filtration Rate ,Research Article - Abstract
Serum uric acid (SUA) levels have a linear relationship with the estimated glomerular filtration rate (eGFR). It is unclear whether further changes, subsequent to normal level of SUA can attenuate eGFR decline in a healthy population, so we aimed to determine the normal level of SUA that can contribute to preventing kidney dysfunction. In this retrospective cohort study from Japan, annual health checkup data from 2009 to 2014 was collected. After propensity score matching (1:1), data from 2,634 individuals with basal SUA ≤7.0 mg/dL (normal; mean age, 39 y; mean eGFR, 80.8 mL/min/1.73 m2) and 1,642 individuals with basal SUA >7.0 mg/dL (elevated; mean age, 42 y; mean eGFR, 75.0 mL/min/1.73 m2) were collected to determine the relationship between followed-up SUA level and the rate of change in eGFR. In individuals with normal level SUA at baseline, the elevation of SUA (>7.0 mg/dL) accelerated eGFR decline compared to those with normal SUA levels at 5-year follow-up (−4.1 ± 9.6% vs −9.9 ± 9.0%, p < .0001). Digression of SUA level (≤7.0 mg/dL) reduced eGFR decline compared with persistent SUA level over 7.0 mg/dL (−1.5 ± 11.5% vs −7.0 ± 10.1, p < .0001). In multiple linear regression analysis, there was strong association between the rate of change in SUA and eGFR in individuals with basal SUA ≤7.0 and >7.0 mg/dL (standardized coefficient; −0.3348, p < .001 and −.2523, p < .001, respectively). Subsequent to normal level of SUA (under 7.0 mg/dL) may contribute to a decrease in eGFR decline in apparently healthy men.
- Published
- 2021
- Full Text
- View/download PDF
8. Inhibition of urea transporter ameliorates uremic cardiomyopathy in chronic kidney disease
- Author
-
Janet D. Klein, Fitra Rianto, Lin Tan, Ying Huang, Jeff M. Sands, Manshu Yu, Akihiro Kuma, Xiaonan H. Wang, and Nawazish Naqvi
- Subjects
0301 basic medicine ,Male ,medicine.medical_specialty ,Urea transporter ,Cardiac fibrosis ,medicine.medical_treatment ,Heart Ventricles ,Cardiomyopathy ,Cardiomegaly ,Peptidyl-Dipeptidase A ,urologic and male genital diseases ,Kidney ,Biochemistry ,Article ,Muscle hypertrophy ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Fibrosis ,Transforming Growth Factor beta ,Internal medicine ,Renin–angiotensin system ,Genetics ,medicine ,Animals ,Urea ,RNA, Messenger ,Renal Insufficiency, Chronic ,Molecular Biology ,biology ,business.industry ,Membrane Transport Proteins ,medicine.disease ,Nephrectomy ,female genital diseases and pregnancy complications ,Actins ,Mice, Inbred C57BL ,030104 developmental biology ,Endocrinology ,Hypertension ,biology.protein ,business ,Cardiomyopathies ,030217 neurology & neurosurgery ,Biotechnology ,Kidney disease - Abstract
Uremic cardiomyopathy, characterized by hypertension, cardiac hypertrophy, and fibrosis, is a complication of chronic kidney disease (CKD). Urea transporter (UT) inhibition increases the excretion of water and urea, but the effect on uremic cardiomyopathy has not been studied. We tested UT inhibition by dimethylthiourea (DMTU) in 5/6 nephrectomy mice. This treatment suppressed CKD-induced hypertension and cardiac hypertrophy. In CKD mice, cardiac fibrosis was associated with upregulation of UT and vimentin abundance. Inhibition of UT suppressed vimentin amount. Left ventricular mass index in DMTU-treated CKD was less compared with non-treated CKD mice as measured by echocardiography. Nephrectomy was performed in UT-A1/A3 knockout (UT-KO) to further confirm our finding. UT-A1/A3 deletion attenuates the CKD-induced increase in cardiac fibrosis and hypertension. The amount of α-smooth muscle actin and tgf-β were significantly less in UT-KO with CKD than WT/CKD mice. To study the possibility that UT inhibition could benefit heart, we measured the mRNA of renin and angiotensin-converting enzyme (ACE), and found both were sharply increased in CKD heart; DMTU treatment and UT-KO significantly abolished these increases. Conclusion: Inhibition of UT reduced hypertension, cardiac fibrosis, and improved heart function. These changes are accompanied by inhibition of renin and ACE.
- Published
- 2020
9. UT-A1/A3 knockout mice show reduced fibrosis following unilateral ureteral obstruction
- Author
-
Carla LaShannon Ellis, Jeff M. Sands, Janet D. Klein, Akihiro Kuma, Faten Hassounah, Fitra Rianto, Xiaonan H. Wang, and Eva L. Rodriguez
- Subjects
Male ,medicine.medical_specialty ,Physiology ,Urea transporter ,Renal urea handling ,Vimentin ,urologic and male genital diseases ,Kidney ,Severity of Illness Index ,Masson's trichrome stain ,Fibrosis ,Transforming Growth Factor beta ,Internal medicine ,Renal fibrosis ,Medicine ,Animals ,Mice, Knockout ,biology ,business.industry ,urogenital system ,Membrane Transport Proteins ,medicine.disease ,female genital diseases and pregnancy complications ,Actins ,Extracellular Matrix ,Mice, Inbred C57BL ,Disease Models, Animal ,Endocrinology ,Knockout mouse ,biology.protein ,Female ,Kidney Diseases ,business ,Kidney disease ,Ureteral Obstruction ,Research Article - Abstract
Renal fibrosis is a major contributor to the development and progression of chronic kidney disease. A low-protein diet can reduce the progression of chronic kidney disease and reduce the development of renal fibrosis, although the mechanism is not well understood. Urea reabsorption into the inner medulla is regulated by inner medullary urea transporter (UT)-A1 and UT-A3. Inhibition or knockout of UT-A1/A3 will reduce interstitial urea accumulation, which may be beneficial in reducing renal fibrosis. To test this hypothesis, the effect of unilateral ureteral obstruction (UUO) was compared in wild-type (WT) and UT-A1/A3 knockout mice. UUO causes increased extracellular matrix associated with increases in transforming growth factor-β, vimentin, and α-smooth muscle actin (α-SMA). In WT mice, UUO increased the abundance of three markers of fibrosis: transforming growth factor-β, vimentin, and α-SMA. In contrast, in UT-A1/A3 knockout mice, the increase following UUO was significantly reduced. Consistent with the Western blot results, immunohistochemical staining showed that the levels of vimentin and α-SMA were increased in WT mice with UUO and that the increase was reduced in UT-A1/A3 knockout mice with UUO. Masson’s trichrome staining showed increased collagen in WT mice with UUO, which was reduced in UT-A1/A3 knockout mice with UUO. We conclude that reduced UT activity reduces the severity of renal fibrosis following UUO.
- Published
- 2020
10. Relationship between abdominal adiposity and incident chronic kidney disease in young- to middle-aged working men: a retrospective cohort study
- Author
-
Akihiko Kato, Masatoshi Kawashima, Akihiro Kuma, Bungo Uchino, Kazuhiko Enta, Yutaka Otsuji, Masahito Tamura, and Yoko Ochiai
- Subjects
Adult ,Male ,Aging ,medicine.medical_specialty ,Waist ,Physiology ,030232 urology & nephrology ,Renal function ,030204 cardiovascular system & hematology ,urologic and male genital diseases ,Body Mass Index ,Cohort Studies ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Japan ,Reference Values ,Risk Factors ,Physiology (medical) ,Internal medicine ,Diabetes Mellitus ,medicine ,Humans ,Renal Insufficiency, Chronic ,Risk factor ,Adiposity ,Retrospective Studies ,business.industry ,Retrospective cohort study ,Odds ratio ,Middle Aged ,medicine.disease ,Obesity ,Nephrology ,Obesity, Abdominal ,Hypertension ,Waist Circumference ,business ,Body mass index ,Follow-Up Studies ,Glomerular Filtration Rate ,Kidney disease - Abstract
Obesity is a risk factor for the development of chronic kidney disease (CKD). However, it remains to be fully examined whether fatness is more useful in predicting incident CKD. We aimed this study to determine the association of body fat, body mass index and waist circumference (WC) with subsequent changes in estimated glomerular filtration rate (eGFR) and incident CKD in young- to middle-aged working men. We analyzed data from annual health check-up in male workers aged from 20 to 60 years with basal eGFR of 60–90 mL/min/1.73 m2. Cut-off values of parameters and odds ratio (OR) for the incident CKD were calculated by receiver operator characteristics analysis andχ2 test, respectively. We also tested trends of changes in eGFR according to changes in WC in each age decade. There were 8,015 men participants. During the 5-year follow-up, 11.0% of the participants (N = 878) had developed to incident CKD. When basal WC was greater than 80.0 cm, which was decided by Youden’s Index, there was a significantly higher risk of incident CKD [OR 1.57 (95% confident interval 1.35–1.84)]. Changes in WC over 5 years were significantly related to eGFR decline in young men ( 80.0 cm is a risk factor for incident CKD and strongly associated with a decline in eGFR in the young- to middle-aged working healthy men.
- Published
- 2018
11. Monocarboxylate Transporter-1 Mediates the Protective Effects of Neutral-pH Bicarbonate/Lactate-Buffered Peritoneal Dialysis Fluid on Cell Viability and Apoptosis
- Author
-
Tetsu Miyamoto, Yoshikazu Harada, Ryota Serino, Nana Ishimatsu, Hiroto Izumi, Yutaka Otsuji, Masahito Tamura, Yoko Nakano, Akihiro Kuma, and Yumi Furuno
- Subjects
0301 basic medicine ,Small interfering RNA ,Bicarbonate ,030232 urology & nephrology ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Medicine ,Viability assay ,Gene knockdown ,TUNEL assay ,biology ,business.industry ,fungi ,Transporter ,Hematology ,Molecular biology ,body regions ,030104 developmental biology ,Monocarboxylate transporter 1 ,nervous system ,Biochemistry ,chemistry ,Nephrology ,Apoptosis ,biology.protein ,business - Abstract
We investigated the effects of bicarbonate/lactate-buffered peritoneal dialysis fluid (B/L-PDF) and lactate-buffered PDF (L-PDF) on cell viability and apoptosis, focusing on monocarboxylate transporters (MCTs). MCT-1 transports lactate into cells. Cell viability and apoptosis of human peritoneal mesothelial cells (HPMCs) were examined by water-soluble tetrazolium salt-1 and TUNEL assays, respectively. The relative number of viable HPMCs was significantly decreased by L-PDF at 48 h (8.8 ± 0.4%) compared with cells cultured in M199, but not by B/L-PDF (66.7 ± 1.1%). Apoptosis was markedly induced by L-PDF at 48 h (69.3 ± 16.2%), but not by B/L-PDF (2.6 ± 0.3%). Knockdown of MCT-1 by small interfering RNA (siRNA) attenuated the L-PDF-induced reduction of viable cells and increased apoptosis compared with control siRNA, but MCT-4 knockdown had no effect. B/L-PDF had lesser effects on cell viability and apoptosis of HPMCs compared with L-PDF. These results suggest that B/L-PDF biocompatibility occurs by avoiding the induction of apoptosis in HPMCs.
- Published
- 2016
12. Biocompatibility of neutral bicarbonate-buffered peritoneal dialysis solution
- Author
-
Akihiro Kuma, Masahito Tamura, and Tetsu Miyamoto
- Subjects
Biocompatibility ,Computer Networks and Communications ,business.industry ,medicine.medical_treatment ,Bicarbonate ,030232 urology & nephrology ,Pharmacology ,Peritoneal dialysis ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,chemistry ,Hardware and Architecture ,030220 oncology & carcinogenesis ,medicine ,business ,Software - Published
- 2016
13. 465 The factors which influences to the serum adiponectin level among japanese workers with declining renal function
- Author
-
Taro Okazaki, Tomoko Yokogawa, Masatoshi Kawashima, Kazuhiko Enta, and Akihiro Kuma
- Subjects
Health examination ,business.industry ,Linear regression ,Physiology ,Medicine ,Renal function ,Regression analysis ,business ,Serum adiponectin ,Body mass index ,Lipoprotein - Abstract
Introduction This study aimed to investigate factors which influences to the serum adiponectin level among Japanese workers with declining renal function. Methods This study involved all participants who had undergone measurement of the serum adiponectin level at least one time at annual health examination during the period from 2008 to 2016 among Japanese workers in a railway company. We conducted analyses of participants with declining renal function. For those with serum adiponectin levels measured multiple times during this period, health examination data obtained during the year when the most recent level was measured were used for analysis. The participants were classified into 4 categories according to eGFR. Categories G3a, G3b, G4, and G5 were 45–59, 30–44, 15–29 and 2 ; and the serum adiponectin level was obtained for each group. Next, factors’ affecting the serum adiponectin level was investigated among indices of lifestyle-related diseases and different lifestyles measured at health examination. The serum adiponectin level was used as a dependent variable, while eGFR, indices of lifestyle-related diseases, and different lifestyles were used as independent variables. Multiple regression analysis was performed to identify items significantly influences to the serum adiponectin level. Results This study included 646 participants, and was 98.3% male. The mean serum adiponectin level was 8.6 μg/mL (1.8–32.5). The levels of the categories divided by eGFRs were 8.1 (G3a), 10.3 (G3b), 13.5 (G4), and 15.6 (G5). Multiple regression analysis identified four items as being significantly associated with the serum adiponectin level (standardised regression coefficient): eGFR (0.334), body mass index (0.241), the presence/absence of regular sleeping habits (0.114), and low-density lipoprotein (0.077). Conclusions In the participants with declining renal function, the serum adiponectin level was significantly associated with some items. Estimated GFR showed the greatest standardised regression coefficient, indicating that eGFR strongly affects the serum adiponectin level.
- Published
- 2018
14. Strong expression of polypeptide N-acetylgalactosaminyltransferase 3 independently predicts shortened disease-free survival in patients with early stage oral squamous cell carcinoma
- Author
-
Kimitoshi Kohno, Yasuyuki Sasaguri, Toshiyuki Nakayama, Yoshikazu Harada, Hirotsugu Noguchi, Yuichiro Kawatsu, Hiroshi Hijioka, Hidetaka Uramoto, Akihiko Miyawaki, Tomoko Kimura, Sohsuke Yamada, Hiroto Izumi, Akihiro Kuma, Ryoichi Oya, Shohei Kitada, and Ke-Yong Wang
- Subjects
Male ,Oncology ,Cytoplasm ,Cancer Research ,Pathology ,Glycosylation ,Metastasis ,Pathogenesis ,Neoplasm Metastasis ,Stage (cooking) ,Aged, 80 and over ,Mouth neoplasm ,Cell Differentiation ,General Medicine ,Middle Aged ,Disease-free survival (DFS) ,Prognosis ,Immunohistochemistry ,Neoplasm Proteins ,Gene Expression Regulation, Neoplastic ,Lymphatic system ,Carcinoma, Squamous Cell ,Disease Progression ,N-Acetylgalactosaminyltransferases ,Female ,Mouth Neoplasms ,Original Article ,Erratum ,Adult ,medicine.medical_specialty ,Biology ,Polypeptide N-acetylgalactosaminyltransferase 3 (GalNAc-T3) ,Disease-Free Survival ,Young Adult ,Cell Line, Tumor ,Internal medicine ,Biomarkers, Tumor ,Cell Adhesion ,medicine ,Humans ,Neoplasm Invasiveness ,Aged ,Vessel invasion ,Gene Expression Profiling ,Early stage OSCC (ESOSCC) ,medicine.disease ,Oral squamous cell carcinoma (OSCC) ,carbohydrates (lipids) ,Microscopy, Fluorescence ,Tumor progression ,Cancer cell ,Neoplasm Recurrence, Local - Abstract
The polypeptide N-acetylgalactosaminyltransferase (GalNAc-Ts) family of enzymes regulates the critical initial steps of mucin-type O-glycosylation. Among GalNAc-Ts that may significantly influence cancer biology, thus affecting cell differentiation, adhesion, invasion, and/or metastasis, GalNAc-T3 exhibits a high expression in several human cancers, closely associated with tumor progression and a poor prognosis. However, the expression pattern of GalNAc-T3 in oral squamous cell carcinoma (OSCC) remains obscure. Since postoperative recurrence of even early stage OSCC (ESOSCC) occurs at an early phase, significantly affecting their clinical course and worse outcome, the identification of clinically significant accurate biomarkers is needed. Therefore, we investigated the correlation between the immunohistochemical GalNAc-T3 expression and various clinicopathological characteristics and recurrence using 110 paraffin-embedded tumor samples obtained from patients with surgically resected ESOSCC (T1–2N0). Recurrence was recognized in 37 of 110 (33.6 %) patients. The GalNAc-T3 expression was considered to be strongly positive when 20 % or more of the cancer cells showed positive cytoplasmic staining. Consequently, a strong expression of GalNAc-T3 was observed in 40 patients (36.4 %), showing a close relationship to poor differentiation, the presence of lymphatic and vascular invasion, and recurrence. Univariate and multivariate analyses further demonstrated that the patients with a strong GalNAc-T3+ status had markedly lower disease-free survival (DFS) rates, especially within the first 2 years postoperatively. Therefore, GalNAc-T3 might play a role in the pathogenesis of ESOSCC recurrence, and its immunohistochemical detection potentially predicts a shorter DFS and may be a useful parameter for providing clinical management against ESOSCC in the early postoperative phase. Electronic supplementary material The online version of this article (doi:10.1007/s13277-015-3928-7) contains supplementary material, which is available to authorized users.
- Published
- 2015
15. Mitochondrial Transcription Factor A and Mitochondrial Genome as Molecular Targets for Cisplatin-Based Cancer Chemotherapy
- Author
-
Yoichiro Yoshida, Ke Yong Wang, Kimitoshi Kohno, Mayu Takahashi, Hiroto Izumi, Masakazu Hirakawa, Akihiro Kuma, Shinji Matsumoto, Tomoko Kurita, and Yoshikazu Harada
- Subjects
Mitochondrial DNA ,medicine.medical_treatment ,cisplatin ,Antineoplastic Agents ,Review ,Biology ,Mitochondrion ,Catalysis ,cancer chemotherapy ,Mitochondrial Proteins ,Inorganic Chemistry ,lcsh:Chemistry ,Neoplasms ,medicine ,Animals ,Humans ,Physical and Theoretical Chemistry ,Molecular Biology ,Transcription factor ,lcsh:QH301-705.5 ,Spectroscopy ,Cisplatin ,Chemotherapy ,mtDNA ,Organic Chemistry ,General Medicine ,TFAM ,Mitochondria ,Computer Science Applications ,Cell biology ,DNA-Binding Proteins ,Gene Expression Regulation, Neoplastic ,Oxidative Stress ,lcsh:Biology (General) ,lcsh:QD1-999 ,Drug Resistance, Neoplasm ,Apoptosis ,Genome, Mitochondrial ,Cancer cell ,prognosis ,mtTFA ,DNA Damage ,Transcription Factors ,medicine.drug - Abstract
Mitochondria are important cellular organelles that function as control centers of the energy supply for highly proliferative cancer cells and regulate apoptosis after cancer chemotherapy. Cisplatin is one of the most important chemotherapeutic agents and a key drug in therapeutic regimens for a broad range of solid tumors. Cisplatin may directly interact with mitochondria, which can induce apoptosis. The direct interactions between cisplatin and mitochondria may account for our understanding of the clinical activity of cisplatin and development of resistance. However, the basis for the roles of mitochondria under treatment with chemotherapy is poorly understood. In this review, we present novel aspects regarding the unique characteristics of the mitochondrial genome in relation to the use of platinum-based chemotherapy and describe our recent work demonstrating the importance of the mitochondrial transcription factor A (mtTFA) expression in cancer cells.
- Published
- 2015
16. Impact of low-density lipoprotein cholesterol on decline in estimated glomerular filtration rate in apparently healthy young to middle-aged working men
- Author
-
Yoko Ochiai, Bungo Uchino, Masatoshi Kawashima, Kazuhiko Enta, Akihiro Kuma, Yutaka Otsuji, Masahito Tamura, and Akihiko Kato
- Subjects
Adult ,Male ,medicine.medical_specialty ,Physiology ,Population ,030232 urology & nephrology ,Renal function ,030204 cardiovascular system & hematology ,Gastroenterology ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Japan ,Reference Values ,Risk Factors ,Physiology (medical) ,Internal medicine ,Diabetes mellitus ,medicine ,Humans ,Young adult ,Renal Insufficiency, Chronic ,education ,Occupational Health ,Dyslipidemias ,Retrospective Studies ,education.field_of_study ,business.industry ,Odds ratio ,Cholesterol, LDL ,Middle Aged ,medicine.disease ,Confidence interval ,Endocrinology ,Nephrology ,Metabolic syndrome ,business ,Dyslipidemia ,Glomerular Filtration Rate - Abstract
It remains to be fully clarified whether there is a relationship between uncontrolled dyslipidemia and decline in estimated glomerular filtration rate (eGFR) in the general population. Therefore, this study’s aim was to test the association of dyslipidemia with changes in eGFR in apparently healthy working men. We retrospectively examined the annual medical check-up list of 14,510 male workers aged 20–60 years with eGFR ≥ 60 mL/min/1.73 m2 at baseline, and then evaluated the association of the changes in the check-up parameters with a decline in eGFR during the 5-year observation period. Mean age and eGFR were 38.5 years and 82.3 mL/min/1.73 m2 at baseline, respectively. Evaluated low-density lipoprotein cholesterol (LDL-C) (≥140 mg/dL) was a strong indicator of CKD development in participants (basal eGFR 60–90 mL/min/1.73 m2) without hypertension [odds ratio (95% confidence interval): 1.46 (1.12–1.90)] or diabetes mellitus (DM) [1.49 (1.23–1.82)]. When LDL-C normalized under 140 mg/dL during follow-up, the decline in eGFR was smaller in non-hypertensive participants [−5.9 (−14.4 to −0.9) vs −13.4 (−18.4 to −4.5) mL/min/1.73 m2, p
- Published
- 2017
17. Hypersensitivity to Aurora Kinase Inhibitors in Cells Resistant against Platinum- Containing Anticancer Agents
- Author
-
Masaki Akiyama, Ke-Yong Wang, Koji Yamaguchi, Yoshikazu Harada, Ryoichi Oya, Noriaki Kitamura, Akihiro Kuma, Hiroto Izumi, Takahiro Yamaguchi, Kimitoshi Kohno, and Yoshiko Iwai
- Subjects
Cancer Research ,Organoplatinum Compounds ,medicine.medical_treatment ,Aurora inhibitor ,Aurora B kinase ,Antineoplastic Agents ,Biology ,Pharmacology ,Targeted therapy ,chemistry.chemical_compound ,Aurora kinase ,Aurora Kinases ,Cell Line, Tumor ,medicine ,Humans ,Protein Kinase Inhibitors ,Cisplatin ,Kinase ,Organophosphates ,Oxaliplatin ,ZM447439 ,chemistry ,Drug Resistance, Neoplasm ,Benzamides ,Quinazolines ,Molecular Medicine ,medicine.drug - Abstract
The aurora kinases are serine/threonine kinases that are essential for mitosis and contribute to tumorigenesis. Therefore, aurora kinases hold promise for molecularly targeted therapy. In the present study, we demonstrated that aurora B kinase (AURKB) is overexpressed in both cisplatin- and oxaliplatin-resistant cells. Downregulation of AURKB sensitized cells to both cisplatin and oxaliplatin, but not to paclitaxel, 5-FU or hydrogen peroxide. Interestingly, we found that both cisplatin- and oxaliplatin-resistant cells were hypersensitive to the AURKB specific inhibitors, AZD1152 HQPA and ZM447439, suggesting that both cisplatin- and oxaliplatinresistant cells develop an addiction to AURKB. These data provide evidence that aurora kinase inhibitors can overcome both cisplatin and oxaliplatin resistance. Therefore, AURKB inhibitors could offer potential benefits if used after first-line platinum-based chemotherapy.
- Published
- 2014
18. Polypeptide N-acetylgalactosaminyl transferase 3 independently predicts high-grade tumours and poor prognosis in patients with renal cell carcinomas
- Author
-
Atsunori Nabeshima, Hirotsugu Noguchi, Yasuyuki Sasaguri, Nakano R, Tetsuro Matsumoto, Ke-Yong Wang, Sohsuke Yamada, Shohei Kitada, Kimitoshi Kohno, Akihiro Kuma, Takashi Tasaki, Ouchi S, Hiroto Izumi, and Shohei Shimajiri
- Subjects
Adult ,Male ,Cancer Research ,Pathology ,medicine.medical_specialty ,Poor prognosis ,renal cell carcinoma ,Cell ,Biology ,Cohort Studies ,Cell Line, Tumor ,parasitic diseases ,medicine ,Carcinoma ,Biomarkers, Tumor ,Transferase ,Humans ,In patient ,vascular invasion ,Molecular Diagnostics ,Carcinoma, Renal Cell ,Aged ,Retrospective Studies ,Aged, 80 and over ,Middle Aged ,medicine.disease ,Prognosis ,Kidney Neoplasms ,carbohydrates (lipids) ,medicine.anatomical_structure ,Oncology ,Cell culture ,GalNAc-T6 ,Cancer research ,N-Acetylgalactosaminyltransferases ,lipids (amino acids, peptides, and proteins) ,GalNAc-T3 ,Female ,Neoplasm Grading - Abstract
Background: The polypeptide N-acetylgalactosaminyltransferases (GalNAc-Ts) family of enzymes regulates the initial steps of mucin-type O-glycosylation. N-acetylgalactosaminyltransferases might show novel patterns of GalNAc-T glycosylation on tumour-derived proteins, which could influence cancer biology, but its mechanisms are unclear. We investigated the association of GalNAc-T3 and -T6 expressions with clinicopathological features and prognoses of patients with renal cell carcinomas (RCCs). Methods: Expressions of GalNAc-T3/6 and cell-adhesion molecules were analysed immunohistochemically in 254 paraffin-embedded tumour samples of patients with RCC. Results: Of 138 GalNAc-T3+ cases, 46 revealed significant co-expression with GalNAc-T6. N-acetylgalactosaminyltransferases-3+ expression showed a close relationship to poor clinical performance and large tumour size, or pathologically high Fuhrman's grading, and presence of vascular invasion and necrosis. The GalNAc-T3-positivity potentially suppressed adhesive effects with a significantly low β-catenin expression. Univariate and multivariate analyses showed the GalNAc-T3+ group, but not the GalNAc-T6+ group, to have significantly worse survival rates. Conclusion: N-acetylgalactosaminyltransferases-3 expression independently predicts high-grade tumour and poor prognosis in patients with RCC, and may offer a therapeutic target against RCC.
- Published
- 2013
19. [Mechanism of and Therapy for Kidney Fibrosis]
- Author
-
Akihiro Kuma, Masahito Tamura, and Yutaka Otsuji
- Subjects
0301 basic medicine ,Epithelial-Mesenchymal Transition ,medicine.medical_treatment ,Renal function ,Protein Serine-Threonine Kinases ,Kidney ,03 medical and health sciences ,Fibrosis ,Transforming Growth Factor beta ,medicine ,Animals ,Humans ,Epithelial–mesenchymal transition ,Molecular Targeted Therapy ,Wnt Signaling Pathway ,Kidney transplantation ,Dialysis ,Uremia ,Inflammation ,urogenital system ,business.industry ,TOR Serine-Threonine Kinases ,Public Health, Environmental and Occupational Health ,Acute kidney injury ,Antibodies, Monoclonal ,General Medicine ,medicine.disease ,030104 developmental biology ,medicine.anatomical_structure ,Cancer research ,Kidney Diseases ,business ,Kidney disease - Abstract
Fibrosis occurs in systemic tissues other than the brain and finally induces dysfunction of the fibrotic organ. Kidney fibrosis is related to scarring after acute kidney injury and the progression of chronic kidney disease. Kidney function decreases with the progression of kidney fibrosis. As fibrotic tissue cannot return to its original status, advanced kidney fibrosis requires the administration of dialysis or kidney transplantation. Thus, elucidation the mechanism of kidney fibrosis is an important research theme. The proliferation and activation of (myo) fibroblasts and the excessive production of an extracellular matrix are common mechanisms in fibrosis in many organs, but it seems that kidney fibrosis has specific pathways. Tubular epithelial, mesangial cells, and erythropoietin producing cells, which exist only in the kidney, participate in forming kidney fibrosis. This review highlights an understanding of the cells and their underlying mechanisms, which are specific to kidney fibrosis process: transforming growth factor-β (TGF-β), epithelial-mesenchymal transition, wingless/int-1 (WNT) signaling, renal anemia, and uremia. Finally, we describe potential therapies that focus on the mechanisms of kidney fibrosis: anti-TGF-β antibody and mammalian target of rapamycin (mTOR).
- Published
- 2016
20. Forced Expression of ZNF143 Restrains Cancer Cell Growth
- Author
-
Kimitoshi Kohno, Masaki Akiyama, Takahiro Yamaguchi, Yoshihiro Yasuniwa, Akihiro Kuma, Hiroto Izumi, and Noriaki Kitamura
- Subjects
cell division ,Cancer Research ,education.field_of_study ,Cell cycle checkpoint ,ZNF143 ,cell cycle ,Cell division ,Cell ,Population ,Biology ,Cell cycle ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,lcsh:RC254-282 ,Article ,Cell biology ,medicine.anatomical_structure ,Oncology ,Cell culture ,Gene expression ,Cancer cell ,medicine ,education - Abstract
We previously reported that the transcription factor Zinc Finger Protein 143 (ZNF143) regulates the expression of genes associated with cell cycle and cell division, and that downregulation of ZNF143 induces cell cycle arrest at G2/M. To assess the function of ZNF143 expression in the cell cycle, we established two cells with forced expression of ZNF143 derived from PC3 prostate cancer cell lines. These cell lines overexpress genes associated with cell cycle and cell division, such as polo-like kinase 1 (PLK1), aurora kinase B (AURKB) and some minichromosome maintenance complex components (MCM). However, the doubling time of cells with forced expression of ZNF143 was approximately twice as long as its control counterpart cell line. Analysis following serum starvation and re-seeding showed that PC3 cells were synchronized at G1 in the cell cycle. Also, ZNF143 expression fluctuated, and was at its lowest level in G2/M. However, PC3 cells with forced expression of ZNF143 synchronized at G2/M, and showed lack of cell cycle-dependent fluctuation of nuclear expression of MCM proteins. Furthermore, G2/M population of both cisplatin-resistant PCDP6 cells over-expressing ZNF143 (derived from PC3 cells) and cells with forced expression of ZNF143 was significantly higher than that of each counterpart, and the doubling time of PCDP6 cells is about 2.5 times longer than that of PC3 cells. These data suggested that fluctuations in ZNF143 expression are required both for gene expression associated with cell cycle and for cell division.
- Published
- 2011
21. Role of WNT10A-expressing kidney fibroblasts in acute interstitial nephritis
- Author
-
Yutaka Otsuji, Yoshiko Iwai, Ke-Yong Wang, Kimitoshi Kohno, Hiroto Izumi, Noriaki Kitamura, Masahito Tamura, Akihiro Kuma, Sohsuke Yamada, and Takahiro Yamaguchi
- Subjects
Male ,Pathology ,medicine.medical_specialty ,Clinical Pathology ,Renal function ,lcsh:Medicine ,Apoptosis ,Pathology and Laboratory Medicine ,Kidney ,Diagnostic Medicine ,Fibrosis ,Molecular Cell Biology ,Medicine and Health Sciences ,medicine ,Humans ,lcsh:Science ,Aged ,Multidisciplinary ,biology ,business.industry ,lcsh:R ,Wnt signaling pathway ,Biology and Life Sciences ,Kidney metabolism ,Cell Biology ,Fibroblasts ,medicine.disease ,Actins ,Extracellular Matrix ,Fibronectins ,Wnt Proteins ,Fibronectin ,Oxidative Stress ,medicine.anatomical_structure ,Gene Expression Regulation ,Nephrology ,Acute Disease ,biology.protein ,Nephritis, Interstitial ,lcsh:Q ,Cellular Structures and Organelles ,business ,Wound healing ,Nephritis ,Research Article - Abstract
WNT signaling mediates various physiological and pathological processes. We previously showed that WNT10A is a novel angio/stromagenic factor involved in such processes as tumor growth, wound healing and tissue fibrosis. In this study, we investigated the role of WNT10A in promoting the fibrosis that is central to the pathology of acute interstitial nephritis (AIN). We initially asked whether there is an association between kidney function (estimated glomerular filtration rate; eGFR) and WNT10A expression using kidney biopsies from 20 patients with AIN. Interestingly, patients with WNT10A expression had significantly lower eGFR than WNT10A-negative patients. However, changes in kidney function were not related to the level of expression of other WNT family members. Furthermore, there was positive correlation between WNT10A and α-SMA expression. We next investigated the involvement of WNT10A in kidney fibrosis processes using COS1 cells, a kidney fibroblast cell line. WNT10A overexpression increased the level of expression of fibronectin and peroxiredoxin 5. Furthermore, WNT10A overexpression renders cells resistant to apoptosis induced by hydrogen peroxide and high glucose. Collectively, WNT10A may induce kidney fibrosis and associate with kidney dysfunction in AIN.
- Published
- 2014
22. SP743ASSOCIATION BETWEEN PLASMA PENTRAXIN-3 LEVELS AND RISK OF ALL-CAUSE MORTALITY IN JAPANESE HEMODIALYSIS PATIENTS WITH NUTRITIONAL RISK
- Author
-
Tetsu Miyamoto, Ken Otsuji, Hiromichi Ueno, Ryota Serino, Mika Matsumoto, Kenichiro Bando, Yutaka Otsuji, Akihiro Kuma, Emi Hasegawa, Yumi Furuno, Nana Ishimatsu, Yoko Fujimoto, and Masahito Tamura
- Subjects
Transplantation ,medicine.medical_specialty ,Nephrology ,business.industry ,medicine.medical_treatment ,Internal medicine ,medicine ,Hemodialysis ,PTX3 protein ,business ,Nutritional risk ,All cause mortality ,Pentraxin-3 - Published
- 2015
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.