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1.
Sci Rep ; 14(1): 926, 2024 01 09.
Article in English | MEDLINE | ID: mdl-38195985

ABSTRACT

Although novel techniques for avoiding incontinence during robot-assisted radical prostatectomy have been developed, long-term oncological outcomes are unknown. The objective of this study was to determine the long-term oncological outcomes and functional outcomes of novel nerve-sparing robot-assisted radical prostatectomy with endopelvic fascia preservation for a single surgeon. Data from 100 patients who underwent structure-preserving prostatectomies performed by a single surgeon were retrospectively analyzed. The median console time was 123 min. Bilateral nerve-sparing was performed in 43% of patients underwent, and 57% underwent unilateral nerve-sparing surgery. Most patients (96%) reached complete pad-zero urinary continence by one year after surgery. Satisfactory erectile function was achieved in 97% of patients who underwent bilateral nerve-sparing surgery, and 80% of patients who underwent unilateral nerve-sparing surgery. The surgical margin was positive for 25% of patients, and the biochemical recurrence-free rate at 5 years was 77%. The cancer-specific survival rate was 100% during the median follow-up period of 4.5 years. Clavien-Dindo grade III complications occurred in 1% of cases. The outcomes for novel nerve-sparing robot-assisted radical prostatectomy with endopelvic fascia preservation were similar to previously reported oncological outcomes, with satisfactory functional outcomes. This operative method may be useful for patients who are eligible for nerve-sparing surgery.


Subject(s)
Robotics , Surgeons , Male , Humans , Retrospective Studies , Prostatectomy , Fascia
2.
Int J Urol ; 30(8): 659-665, 2023 08.
Article in English | MEDLINE | ID: mdl-37130793

ABSTRACT

OBJECTIVES: To determine candidates for extended pelvic lymph node dissection using a novel nomogram to assess the risk of lymph node invasion in Japanese prostate cancer patients in the robotic era. METHODS: A total of 538 patients who underwent robot-assisted radical prostatectomy with extended pelvic lymph node dissection in three hospitals were retrospectively analyzed. Medical records were reviewed uniformly and the following data collected: prostate-specific antigen, age, clinical T stage, primary and secondary Gleason score at prostate biopsy, and percentage of positive core numbers. Finally, data from 434 patients were used for developing the nomogram and data from 104 patients were used for external validation. RESULTS: Lymph node invasion was detected in 47 (11%) and 16 (15%) patients in the development and validation set, respectively. Based on multivariate analysis, prostate-specific antigen, clinical T stage ≥3, primary Gleason score, grade group 5, and percentage of positive cores were selected as variables to incorporate into the nomogram. The area under the curve values were 0.781 for the internal and 0.908 for the external validation, respectively. CONCLUSIONS: The present nomogram can help urologists identify candidates for extended pelvic lymph node dissection concomitant with robot-assisted radical prostatectomy among patients with prostate cancer.


Subject(s)
Prostatic Neoplasms , Robotic Surgical Procedures , Robotics , Male , Humans , Nomograms , Prostate-Specific Antigen , Retrospective Studies , Lymphatic Metastasis/pathology , Lymph Node Excision , Lymph Nodes/surgery , Lymph Nodes/pathology , Prostatic Neoplasms/surgery , Prostatic Neoplasms/pathology , Prostatectomy
3.
Surgery ; 174(2): 234-240, 2023 08.
Article in English | MEDLINE | ID: mdl-37188580

ABSTRACT

BACKGROUND: The surgical and endocrinological outcomes of single-port laparoscopic partial adrenalectomy for patients with aldosterone-producing adenomas are unknown. Precise diagnosis of intra-adrenal aldosterone activity and a precise surgical procedure may improve outcomes. In this study, we aimed to determine the surgical and endocrinological outcomes of single-port laparoscopic partial adrenalectomy with preoperative segmental selective adrenal venous sampling and intraoperative high-resolution laparoscopic ultrasound in patients with unilateral aldosterone-producing adenomas. We identified 53 patients with partial adrenalectomy and 29 patients with laparoscopic total adrenalectomy. Single-port surgery was performed for 37 and 19 patients, respectively. METHODS: A single-center, retrospective cohort study. All patients with unilateral aldosterone-producing adenomas diagnosed by selective adrenal venous sampling and treated surgically between January 2012 and February 2015 were included. Follow-up with biochemical and clinical assessments was set at 1 year after surgery for short-term outcomes and was performed every 3 months after surgery. RESULTS: We identified 53 patients with partial adrenalectomy and 29 patients with laparoscopic total adrenalectomy. Single-port surgery was performed for 37 and 19 patients, respectively. Single-port surgery was associated with shorter operative and laparoscopic times (odds ratio, 0.14; 95% confidence interval, 0.039-0.49; P = .002 and odds ratio, 0.13; 95% confidence interval, 0.032-0.57; P = .006, respectively). All single-port and multi-port partial adrenalectomy cases showed complete short-term (median 1 year) biochemical success, and 92.9% (26 of 28 patients) who underwent single-port partial adrenalectomy and 100% (13 of 13 patients) who underwent multi-port partial adrenalectomy showed complete long-term (median 5.5 years) biochemical success. No complications were observed with single-port adrenalectomy. CONCLUSION: Single-port partial adrenalectomy is feasible after selective adrenal venous sampling for unilateral aldosterone-producing adenomas, with shorter operative and laparoscopic times and a high rate of complete biochemical success.


Subject(s)
Adenoma , Adrenal Gland Neoplasms , Adrenocortical Adenoma , Hyperaldosteronism , Laparoscopy , Humans , Adrenalectomy/methods , Aldosterone , Retrospective Studies , Feasibility Studies , Hyperaldosteronism/diagnosis , Hyperaldosteronism/etiology , Hyperaldosteronism/surgery , Adrenocortical Adenoma/diagnostic imaging , Adrenocortical Adenoma/surgery , Adrenocortical Adenoma/complications , Laparoscopy/adverse effects , Adenoma/diagnostic imaging , Adenoma/surgery , Adenoma/complications , Adrenal Gland Neoplasms/diagnostic imaging , Adrenal Gland Neoplasms/surgery , Adrenal Gland Neoplasms/complications
4.
IJU Case Rep ; 5(4): 304-307, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35795120

ABSTRACT

Introduction: Plasmacytoid variant bladder cancer is a rare variant of urothelial carcinoma that accounts for 1% of bladder cancers. Plasmacytoid variant urothelial carcinoma is characterized by an aggressive phenotype and poor clinical outcomes. Case presentation: A 61-year-old woman presented with gross hematuria. Cystoscopy showed a 16-mm solid tumor. Transurethral resection of the bladder tumor was performed, and the pathological diagnosis was invasive plasmacytoid variant urothelial carcinoma. Although the pathological T stage was pT1, computed tomography showed right obturator lymph node swelling. Since previous reports indicate poor response to chemotherapy for this disease, clinical sequencing was performed. Based on the high tumor mutation burden revealed, pembrolizumab was administered for 4 cycles, and computed tomography showed a partial response. Robot-assisted radical cystectomy was performed, and a pathological complete response including the pelvic lymph node was observed. Conclusion: Pembrolizumab may be a treatment option for plasmacytoid variant urothelial carcinoma following genomic analysis.

5.
Vaccines (Basel) ; 9(12)2021 Dec 20.
Article in English | MEDLINE | ID: mdl-34960251

ABSTRACT

Vaccination has been critical to reducing infections and deaths during the coronavirus disease 2019 (COVID-19) pandemic. While previous studies have investigated attitudes toward taking a vaccine, studies on the determinants of COVID-19 vaccination behavior are scant. We examine what characteristics, including socioeconomic and non-economic factors, are associated with vaccination behavior for COVID-19 in Japan. We use a large nationwide online survey with approximately 10,000 participants. As of September 2021, 85% of the respondents said that they had received or would receive a COVID-19 vaccine. Employing logistic regression analysis on vaccination behavior, we found that vaccination rates are higher among those who are older, married, educated, and/or work in a large company. On the other hand, vaccination rates tend to be lower among the self-employed, younger women, and those with poor mental health. Income did not significantly correlate with vaccination. Medical workers were found to have a relatively high rate of vaccination. Although attitude towards risk and time preference were not crucial factors for vaccination, fear of infection, infection prevention behavior, and agreement with government policies on behavioral restrictions in crisis situations positively correlated with vaccination.

6.
PLoS One ; 16(6): e0252710, 2021.
Article in English | MEDLINE | ID: mdl-34161349

ABSTRACT

The social climate for women studying STEM subjects is changing, but the proportion of women taking STEM subjects in Japan is small. Only 27.9% of university students in the department of science is women in 2019. In this study, we used an online survey to investigate whether randomly providing three types of gender equality information increased the motivation of junior high school students to choose STEM subjects and the motivation of their parents to support that choice. Information on STEM, especially about social equality, and information on math stereotypes and STEM occupations, increased students' motivations for studying STEM. This suggests that providing gender equality information is an effective way to change students' attitudes toward STEM.


Subject(s)
Career Choice , Engineering/education , Gender Equity , Mathematics/education , Motivation , Science/education , Students/psychology , Technology/education , Attitude , Female , Humans , Information Dissemination/methods , Internet , Japan , Male , Occupations/classification , Parents/psychology , Surveys and Questionnaires/statistics & numerical data
7.
Public Underst Sci ; 30(7): 810-826, 2021 10.
Article in English | MEDLINE | ID: mdl-33757362

ABSTRACT

Women are a minority in science, technology, engineering and mathematics academic careers. In particular, few women in Japan choose to study physics and mathematics. In this study, we investigated the factors contributing to the masculine image of physics and mathematics based on the framework of our expanded model. We conducted online questionnaire surveys in Japan and England, and found that physics and mathematics occupations, and mathematical stereotypes were both related to a masculine image. Only in Japan were social factors, such as a person's attitude to intellectual women, related to viewing mathematics as 'masculine'. However, the experience of being told or having heard that the choice of a particular course of studies would make someone less attractive to the opposite sex was evident only in England. This finding suggests that social factors affect the masculine image of physics and mathematics, and that this could vary depending on the country.


Subject(s)
Masculinity , Science , Career Choice , Engineering , Female , Humans , Japan , Male , Mathematics , Physics
8.
Int J Urol ; 26(8): 791-796, 2019 08.
Article in English | MEDLINE | ID: mdl-31081198

ABSTRACT

OBJECTIVES: To examine the effectiveness of intravesical irrigation with physiological saline solution or distilled water for the prevention of bladder recurrence in patients undergoing laparoscopic nephroureterectomy for upper urinary tract urothelial carcinoma. METHODS: This retrospective study involved 109 upper urinary tract urothelial carcinoma patients who underwent laparoscopic nephroureterectomy, and were evaluated at Chiba University Hospital and Yokohama Rosai Hospital between 2001 and 2018. We investigated the outcomes and analyzed various clinical factors including with or without intravesical irrigation related to bladder carcinoma recurrence after surgery. Physiological saline solution or distilled water was used for irrigation, which was carried out only during surgery. RESULTS: The median follow-up period after surgery was 26.1 months. Bladder recurrence was confirmed within 2 years for 45 of the 109 patients in the present study. Irrigation was carried out for 48 cases (distilled water, 26 patients; physiological saline solution, 22 patients). Tumor grade (G1-2 vs G3; P = 0.05) and intravesical irrigation (yes vs no; P = 0.0058) were related to bladder recurrence on univariate analyses. On multivariate analyses, intravesical irrigation was the independent factor involved in the prevention of bladder recurrence (P = 0.0051). Comparison between the irrigation and non-irrigation groups showed that bladder recurrence rates were significantly lower in the irrigation group (irrigation group vs non-irrigation group: 25.0% vs 52.5%, P = 0.0066). There was no significant difference in the recurrence rate between the two solutions used for irrigation. CONCLUSIONS: Intravesical irrigation during surgery of upper urinary tract urothelial carcinoma might decrease postoperative bladder recurrence rates.


Subject(s)
Carcinoma, Transitional Cell/surgery , Kidney Neoplasms/surgery , Neoplasm Recurrence, Local/prevention & control , Nephroureterectomy/methods , Saline Solution/administration & dosage , Ureteral Neoplasms/surgery , Administration, Intravesical , Aged , Female , Follow-Up Studies , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Neoplasm Recurrence, Local/epidemiology , Neoplasm Seeding , Retrospective Studies , Therapeutic Irrigation/methods , Urinary Bladder , Water/administration & dosage
9.
Chem Pharm Bull (Tokyo) ; 65(11): 1085-1088, 2017.
Article in English | MEDLINE | ID: mdl-29093296

ABSTRACT

κ-Opioid receptor agonists with high selectivity over the µ-opioid receptor and peripheral selectivity are attractive targets in the development of drugs for pain. We have previously attempted to create novel analgesics with peripheral selective κ-opioid receptor agonist on the basis of TRK-820. In this study, we elucidated the biological properties of 17-hydroxy-cyclopropylmethyl and 10α-hydroxy derivatives. These compounds were found to have better κ-opioid receptor selectivity and peripheral selectivity than TRK-820.


Subject(s)
Analgesics/pharmacology , Drug Discovery , Morphinans/pharmacology , Pain/drug therapy , Receptors, Opioid, kappa/agonists , Spiro Compounds/pharmacology , Acetic Acid , Analgesics/chemical synthesis , Analgesics/chemistry , Animals , Dose-Response Relationship, Drug , Male , Mice , Mice, Inbred ICR , Models, Molecular , Molecular Conformation , Morphinans/chemical synthesis , Morphinans/chemistry , Pain/chemically induced , Spiro Compounds/chemical synthesis , Spiro Compounds/chemistry , Structure-Activity Relationship
10.
Cardiovasc Diabetol ; 16(1): 125, 2017 10 10.
Article in English | MEDLINE | ID: mdl-29017497

ABSTRACT

BACKGROUND: Dipeptidyl peptidase-4 (DPP-4) inhibitors may have protective effects in the early stage of atherosclerosis in patients with type 2 diabetes, although similar effects in advanced atherosclerosis were not shown in recent randomized placebo-controlled studies. Therefore, we investigated the efficacy of DPP-4 inhibitor on endothelial function and glycemic metabolism compared with high-dose metformin. METHODS: In this multicenter, open-labeled, prospective, randomized, parallel-group comparison study, patients with type 2 diabetes treated with low-dose metformin (500-750 mg/day) were enrolled and randomly assigned to a vildagliptin, a DPP-4 inhibitor, add-on group (Vilda) or a double dose of metformin group (high Met) for 12 weeks. Flow-mediated dilation (FMD) and serum metabolic markers were assessed before and after treatment. In addition, glycemic control and metabolic parameters were also assessed. RESULTS: Ninety-seven subjects (aged 58.7 ± 11.0 years; body mass index, 25.9 ± 4.4 kg/m2; HbA1c, 7.3 ± 0.5%; FMD, 5.8 ± 2.6%) were enrolled. Eight subjects dropped out by the end of the study. There were no significant differences between the two groups in baseline characteristics. After 12 weeks, HbA1c was significantly improved in the Vilda group compared with the high Met group (- 0.80 ± 0.38% vs. - 0.40 ± 0.47%, respectively; p < 0.01). However, there were no significant differences in FMD (- 0.51 [- 1.08-0.06]% vs. - 0.58 [- 1.20-0.04]%). Although the apolipoprotein B/apolipoprotein A1 ratio was significantly reduced in the Vilda group compared with baseline (0.66-0.62; p < 0.01), the change did not differ significantly between the two groups (- 0.04 vs. 0.00; p = 0.27). Adiponectin levels were significantly increased in the Vilda group compared with the high Met group (0.75 µg/mL vs. 0.01 µg/mL; p < 0.01). CONCLUSIONS: Regardless of glycemic improvement, combination therapy of vildagliptin and metformin did not affect endothelial function but may exert favorable effects on adipokine levels and lipid profile in patients with type 2 diabetes without advanced atherosclerosis.


Subject(s)
Adamantane/analogs & derivatives , Diabetes Mellitus, Type 2/drug therapy , Dipeptidyl-Peptidase IV Inhibitors/administration & dosage , Endothelium, Vascular/drug effects , Hypoglycemic Agents/administration & dosage , Metformin/administration & dosage , Nitriles/administration & dosage , Pyrrolidines/administration & dosage , Adamantane/administration & dosage , Adult , Aged , Diabetes Mellitus, Type 2/metabolism , Drug Therapy, Combination , Endothelium, Vascular/physiology , Female , Follow-Up Studies , Humans , Male , Middle Aged , Prospective Studies , Treatment Outcome , Vildagliptin
11.
Nat Chem Biol ; 13(6): 675-680, 2017 06.
Article in English | MEDLINE | ID: mdl-28437394

ABSTRACT

Target-protein degradation is an emerging field in drug discovery and development. In particular, the substrate-receptor proteins of the cullin-ubiquitin ligase system play a key role in selective protein degradation, which is an essential component of the anti-myeloma activity of immunomodulatory drugs (IMiDs), such as lenalidomide. Here, we demonstrate that a series of anticancer sulfonamides NSC 719239 (E7820), indisulam, and NSC 339004 (chloroquinoxaline sulfonamide, CQS) induce proteasomal degradation of the U2AF-related splicing factor coactivator of activating protein-1 and estrogen receptors (CAPERα) via CRL4DCAF15 mediated ubiquitination in human cancer cell lines. Both CRISPR-Cas9-based knockout of DCAF15 and a single amino acid substitution of CAPERα conferred resistance against sulfonamide-induced CAPERα degradation and cell-growth inhibition. Thus, these sulfonamides represent selective chemical probes for disrupting CAPERα function and designate DCAFs as promising drug targets for promoting selective protein degradation in cancer therapy.


Subject(s)
Indoles/pharmacology , Nuclear Proteins/metabolism , RNA Splicing , RNA-Binding Proteins/metabolism , Sulfonamides/metabolism , Antineoplastic Agents/pharmacology , Gene Knockdown Techniques , Humans , Nuclear Proteins/chemistry , Nuclear Proteins/genetics , Proteolysis/drug effects , RNA-Binding Proteins/chemistry , RNA-Binding Proteins/genetics , Sulfonamides/pharmacology
12.
Nat Microbiol ; 2: 17022, 2017 Mar 01.
Article in English | MEDLINE | ID: mdl-28248290

ABSTRACT

Retinoic acid-inducible gene I (RIG-I) receptor recognizes 5'-triphosphorylated RNA and triggers a signalling cascade that results in the induction of type-I interferon (IFN)-dependent responses. Its precise regulation represents a pivotal balance between antiviral defences and autoimmunity. To elucidate the cellular cofactors that regulate RIG-I signalling, we performed two global RNA interference analyses to identify both positive and negative regulatory nodes operating on the signalling pathway during virus infection. These factors were integrated with experimentally and computationally derived interactome data to build a RIG-I protein interaction network. Our analysis revealed diverse cellular processes, including the unfolded protein response, Wnt signalling and RNA metabolism, as critical cellular components governing innate responses to non-self RNA species. Importantly, we identified K-Homology Splicing Regulatory Protein (KHSRP) as a negative regulator of this pathway. We find that KHSRP associates with the regulatory domain of RIG-I to maintain the receptor in an inactive state and attenuate its sensing of viral RNA (vRNA). Consistent with increased RIG-I antiviral signalling in the absence of KHSRP, viral replication is reduced when KHSRP expression is knocked down both in vitro and in vivo. Taken together, these data indicate that KHSRP functions as a checkpoint regulator of the innate immune response to pathogen challenge.


Subject(s)
DEAD Box Protein 58/antagonists & inhibitors , RNA, Viral/immunology , RNA-Binding Proteins/metabolism , Signal Transduction , Trans-Activators/metabolism , HEK293 Cells , Humans , Immunity, Innate , Influenza A Virus, H1N1 Subtype/immunology , Protein Binding , Protein Interaction Mapping , Protein Interaction Maps , Receptors, Immunologic
13.
Proc Natl Acad Sci U S A ; 114(15): 3927-3932, 2017 04 11.
Article in English | MEDLINE | ID: mdl-28356515

ABSTRACT

miRNAs play critical roles in various biological processes by targeting specific mRNAs. Current approaches to identifying miRNA targets are insufficient for elucidation of a miRNA regulatory network. Here, we created a cell-based screening system using a luciferase reporter library composed of 4,891 full-length cDNAs, each of which was integrated into the 3' UTR of a luciferase gene. Using this reporter library system, we conducted a screening for targets of miR-34a, a tumor-suppressor miRNA. We identified both previously characterized and previously uncharacterized targets. miR-34a overexpression in MDA-MB-231 breast cancer cells repressed the expression of these previously unrecognized targets. Among these targets, GFRA3 is crucial for MDA-MB-231 cell growth, and its expression correlated with the overall survival of patients with breast cancer. Furthermore, GFRA3 was found to be directly regulated by miR-34a via its coding region. These data show that this system is useful for elucidating miRNA functions and networks.


Subject(s)
Breast Neoplasms/genetics , Gene Library , Glial Cell Line-Derived Neurotrophic Factor Receptors/genetics , MicroRNAs/genetics , Breast Neoplasms/pathology , Cell Line, Tumor , Female , Gene Expression Regulation, Neoplastic , Genes, Reporter , Glial Cell Line-Derived Neurotrophic Factor Receptors/metabolism , Humans , MicroRNAs/metabolism , RNA Helicases/genetics , Trans-Activators/genetics
14.
Nihon Hinyokika Gakkai Zasshi ; 108(2): 80-86, 2017.
Article in Japanese | MEDLINE | ID: mdl-29669981

ABSTRACT

(Objectives) Radiation induced cystitis (RC) is one of the toxicities we must often treat after radiation therapy for prostate cancer.Some patients require urinary diversion with or without cystectomy.We evaluated the clinical risks and management of RC. (Patients and methods) The clinical records of 303 patients who underwent radiation therapy for prostate cancer (199 only radiation therapy; 104 adjuvant or salvage radiation therapy after radical prostatectomy) between 2005 and 2015 in our institute, were reviewed.We defined RC based on the presence of macrohematuria, not caused by reccurence of prostate cancer or occurrence of bladder cancer. (Results) The median follow up time was 37 months (range 1-132).Thirty patients (9.9%) developed RC.Compared to radiation therapy alone, adjuvant/salvage radiation therapy was found to be a risk for RC (4.5% vs. 20.1%, p< 0.01).Ten out of 30 RC patients needed hospitalization and 6 patients underwent urinary diversion with or without cystectomy.Two patients who underwent urinary diversion without cystectomy were hospitalized for a longer period compared with 4 patients with cystectomy. (Conclusion) Adjuvant/salvage therapy is a risk factor of RC after radiation therapy for prostate cancer.About 2% of the patients needed urinary diversion and cystectomy improved their prognosis.

15.
Cerebellum ; 16(2): 518-524, 2017 04.
Article in English | MEDLINE | ID: mdl-27830516

ABSTRACT

Spinocerebellar ataxia type 31 (SCA31) is known as a late-onset, relatively pure cerebellar form of ataxia, but a longitudinal prospective study on the natural history of SCA31 has not been done yet. In this prospective cohort study, we enrolled 44 patients (mean ± standard deviation 73.6 ± 8.5 years) with genetically confirmed SCA31 from 10 ataxia referral centers in the Nagano area, Japan. Patients were evaluated every year for 4 years using the Scale for the Assessment and Rating of Ataxia (SARA) and the Barthel Index (BI). Of the 176 follow-up visits (91.5%), 161 were completed in this study. Five patients (11.4%) died during the follow-up period, and two patients (4.5%) were lost to follow-up. The annual progression of the SARA score was 0.8 ± 0.1 points/year and that of the BI was -2.3 ± 0.4 points/year (mean ± standard error). Shorter disease duration at baseline was associated with faster progression of the SARA score. Our study indicated the averaged clinical course of SCA31 as follows: the patients develop ataxic symptoms at 58.5 ± 10.3 years, become wheelchair bound at 79.4 ± 1.7 years, and died at 88.5 ± 0.7 years. Our prospective dataset provides important information for clinical trials of forthcoming disease-modifying therapies for cerebellar ataxia. It also represents a useful resource for SCA31 patients and their family members in genetic counseling sessions.


Subject(s)
Spinocerebellar Ataxias/physiopathology , Age of Onset , Aged , Aged, 80 and over , Disease Progression , Family , Female , Follow-Up Studies , Humans , Japan , Kaplan-Meier Estimate , Longitudinal Studies , Male , Middle Aged , Multivariate Analysis , Prospective Studies , Regression Analysis , Severity of Illness Index , Spinocerebellar Ataxias/diagnosis , Spinocerebellar Ataxias/epidemiology , Spinocerebellar Ataxias/rehabilitation , Time Factors , Wheelchairs
16.
Mol Cell Endocrinol ; 441: 134-139, 2017 02 05.
Article in English | MEDLINE | ID: mdl-27514282

ABSTRACT

We report a case of non-familial juvenile primary aldosteronism (PA). Super-selective adrenal venous sampling identified less aldosterone production in the right inferior adrenal segment than others. Bilateral adrenalectomy sparing the segment normalized blood pressure and improved PA. Both adrenals had similar histologies, consisting of a normal adrenal cortex and aldosterone synthase-positive hyperplasia/adenoma. An aldosterone-driving KCNJ5 mutation was detected in the lesions, but not in the histologically normal cortex. After taking into account that the two adrenal glands displayed a similar histological profile, as well as the fact that hyperplastic lesions in both glands exhibited a common KCNJ5 mutation, we conclude that the specific mutation may have occurred at an adrenal precursor mesodermal cell, at an early stage of development; its daughter cells were mixed with non-mutant cells and dispersed into both adrenal glands, resulting into a form of the condition known as genetic mosaicism.


Subject(s)
Adrenal Glands/embryology , Adrenal Glands/pathology , G Protein-Coupled Inwardly-Rectifying Potassium Channels/genetics , Hyperaldosteronism/genetics , Mutation/genetics , Base Sequence , DNA Mutational Analysis , High-Throughput Nucleotide Sequencing , Humans , Immunohistochemistry
17.
PLoS One ; 11(10): e0164255, 2016.
Article in English | MEDLINE | ID: mdl-27711199

ABSTRACT

OBJECTIVES: The DPP-4 inhibitors are incretin-related drugs that improve hyperglycemia in a glucose-dependent manner and have been reported to exert favorable effects on atherosclerosis. However, it has not been fully elucidated whether DPP-4 inhibitors are able to improve endothelial function in patients with type 2 diabetes. Therefore, we investigated the efficacy of sitagliptin, a DPP-4 inhibitor, on endothelial function and glycemic metabolism compared with that of the sulfonylurea glimepiride. MATERIALS AND METHODS: In this multicenter, prospective, randomized parallel-group comparison study, 103 outpatients with type 2 diabetes (aged 59.9 ± 9.9 years with HbA1c levels of 7.5 ± 0.4%) with dietary cure only and/or current metformin treatment were enrolled and randomly assigned to receive sitagliptin or glimepiride therapy once daily for 26 weeks. Flow-mediated dilation (FMD), a comprehensive panel of hemodynamic parameters (Task Force® Monitor), and serum metabolic markers were assessed before and after the treatment. RESULTS: During the study period, no statistically significant change in %FMD was seen in both groups (sitagliptin, 5.6 to 5.6%; glimepiride, 5.6 to 6.0%). Secretory units of islets in transplantation, TNF-α, adiponectin and biological antioxidant potential significantly improved in the sitagliptin group, and superoxide dismutase also tended to improve in the sitagliptin group, while improvements in HbA1c levels were similar between groups. Cardiac index, blood pressure and most other metabolic parameters were not different. CONCLUSIONS: Regardless of glycemic improvement, early sitagliptin therapy did not affect endothelial function but may provide favorable effects on beta-cell function and on inflammatory and oxidative stress in patients with type 2 diabetes without advanced atherosclerosis. TRIAL REGISTRATION: UMIN Clinical Trials Registry System UMIN 000004955.


Subject(s)
Diabetes Mellitus, Type 2/drug therapy , Endothelium/metabolism , Sitagliptin Phosphate/therapeutic use , Sulfonylurea Compounds/therapeutic use , Adiponectin/metabolism , Adult , Aged , Aged, 80 and over , Antioxidants/metabolism , Biomarkers/blood , Blood Pressure , Body Mass Index , Drug Administration Schedule , Female , Glycated Hemoglobin/analysis , Hemodynamics , Humans , Hypoglycemic Agents/therapeutic use , Male , Metformin/therapeutic use , Middle Aged , Prospective Studies , Sitagliptin Phosphate/pharmacology , Sulfonylurea Compounds/pharmacology , Superoxide Dismutase/metabolism , Treatment Outcome , Tumor Necrosis Factor-alpha/metabolism , Young Adult
18.
Biochem Biophys Rep ; 5: 266-271, 2016 Mar.
Article in English | MEDLINE | ID: mdl-28955833

ABSTRACT

We have previously isolated a lactic acid bacterium (LAB), Pediococcus pentosaceus LP28, from the longan fruit Euphoria longana. Since the plant-derived LAB strain produces an extracellular polysaccharide (EPS), in this study, we analyzed the chemical structure and the biosynthesizing genes for the EPS. The EPS, which was purified from the LP28 culture broth, was classified into acidic and neutral EPSs with a molecular mass of about 50 kDa and 40 kDa, respectively. The acidic EPS consisted of glucose, galactose, mannose, and N-acetylglucosamine moieties. Interestingly, since pyruvate residue was detected in the hydrolyzed acidic EPS, one of the four sugars may be modified with pyruvate. On the other hand, the neutral EPS consisted of glucose, mannose, and N-acetylglucosamine; pyruvate was scarcely detected in the polysaccharide molecule. As a first step to deduce the probiotic function of the EPS together with the biosynthesis, we determined the whole genome sequence of the LP28 strain, demonstrating that the genome is a circular DNA, which is composed of 1,774,865 bp (1683 ORFs) with a GC content of 37.1%. We also found that the LP28 strain harbors a plasmid carrying 6 ORFs composed of 5366 bp with a GC content of 36.5%. By comparing all of the genome sequences among the LP28 strain and four strains of P. pentosaceus reported previously, we found that 53 proteins in the LP28 strain display a similarity of less than 50% with those in the four P. pentosaceus strains. Significantly, 4 of the 53 proteins, which may be enzymes necessary for the EPS production on the LP28 strain, were absent in the other four P. pentosaceus strains and displayed less than 50% similarity with other LAB species. The EPS-biosynthetic gene cluster detected only in the LP28 genome consisted of 12 ORFs containing a priming enzyme, five glycosyltransferases, and a putative polysaccharide pyruvyltransferase.

19.
Nihon Hinyokika Gakkai Zasshi ; 107(4): 215-219, 2016.
Article in Japanese | MEDLINE | ID: mdl-29070733

ABSTRACT

(Objectives) To evaluate the safety and oncologic efficacy of laparoscopic radical nephrectomy (LRN) for renal cell carcinoma (RCC) >7 cm, we retrospectively reviewed the clinical outcome and long-term cancer control of patients who underwent LRN in comparison to open radical nephrectomy (ORN). (Patients and methods) The clinical records of 79 patients with RCC >7 cm, who underwent radical nephrectomy (37 LRN; 42 ORN) between 1993 and 2014, were reviewed. (Results) The 2 groups (LRN and ORN) were comparable regarding age, body mass index and mean tumor size (86.5 mm vs. 94.6 mm).The operative time was significantly longer in the LRN group than ORN group (204 min vs. 168 min; p<0.05) and blood loss was significantly lower in the LRN group than in the ORN group (144 ml vs. 930 ml; p<0.05).No statistically significant difference was found in complication rate (10.8% vs. 23.8%) and the 2-year recurrence-free survival rate (85.6% vs. 83.8%). (Conclusion) Despite the longer operative time, LRN for large RCC was associated with lower blood loss. This study provides evidence of the safety and efficacy of LRN for large RCC.

20.
Nihon Hinyokika Gakkai Zasshi ; 106(3): 190-3, 2015 Jul.
Article in Japanese | MEDLINE | ID: mdl-26419077

ABSTRACT

A 68-year-old woman presented with asymptomatic gross hematuria. Computed tomography (CT) scan revealed noninvasive tumor in the right ureteropelvic junction. After diagnosis with right pelvis carcinoma by ureteroscopy, she underwent laparoscopic nephroureterectomy in Aug. 2008. Six months later, hepatic metastasis was detected. Three courses of combination chemotherapy consisting of gemcitabine and cisplatin (GC) were conducted, and then partial response (PR) was achieved. In Aug. 2009, radical metastasectomy for liver metastasis was performed. More than four years and five months after hepatectomy, the patient has achieved a high quality of life.


Subject(s)
Kidney Neoplasms/pathology , Liver Neoplasms/secondary , Pelvic Neoplasms/pathology , Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cisplatin/administration & dosage , Deoxycytidine/administration & dosage , Deoxycytidine/analogs & derivatives , Female , Hepatectomy , Humans , Kidney Neoplasms/drug therapy , Kidney Neoplasms/surgery , Laparoscopy , Liver Neoplasms/surgery , Metastasectomy , Nephrectomy , Pelvic Neoplasms/drug therapy , Pelvic Neoplasms/surgery , Recurrence , Gemcitabine
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