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1.
Trials ; 24(1): 365, 2023 May 30.
Article in English | MEDLINE | ID: mdl-37254217

ABSTRACT

BACKGROUND: An increasing number of older people are living with chronic kidney disease (CKD). Many have complex healthcare needs and are at risk of deteriorating health and functional status, which can adversely affect their quality of life. Comprehensive geriatric assessment (CGA) is an effective intervention to improve survival and independence of older people, but its clinical utility and cost-effectiveness in frail older people living with CKD is unknown. METHODS: The GOAL Trial is a pragmatic, multi-centre, open-label, superiority, cluster randomised controlled trial developed by consumers, clinicians, and researchers. It has a two-arm design, CGA compared with standard care, with 1:1 allocation of a total of 16 clusters. Within each cluster, study participants ≥ 65 years of age (or ≥ 55 years if Aboriginal or Torres Strait Islander (First Nations Australians)) with CKD stage 3-5/5D who are frail, measured by a Frailty Index (FI) of > 0.25, are recruited. Participants in intervention clusters receive a CGA by a geriatrician to identify medical, social, and functional needs, optimise medication prescribing, and arrange multidisciplinary referral if required. Those in standard care clusters receive usual care. The primary outcome is attainment of self-identified goals assessed by standardised Goal Attainment Scaling (GAS) at 3 months. Secondary outcomes include GAS at 6 and 12 months, quality of life (EQ-5D-5L), frailty (Frailty Index - Short Form), transfer to residential aged care facilities, cost-effectiveness, and safety (cause-specific hospitalisations, mortality). A process evaluation will be conducted in parallel with the trial including whether the intervention was delivered as intended, any issue or local barriers to intervention delivery, and perceptions of the intervention by participants. The trial has 90% power to detect a clinically meaningful mean difference in GAS of 10 units. DISCUSSION: This trial addresses patient-prioritised outcomes. It will be conducted, disseminated and implemented by clinicians and researchers in partnership with consumers. If CGA is found to have clinical and cost-effectiveness for frail older people with CKD, the intervention framework could be embedded into routine clinical practice. The implementation of the trial's findings will be supported by presentations at conferences and forums with clinicians and consumers at specifically convened workshops, to enable rapid adoption into practice and policy for both nephrology and geriatric disciplines. It has potential to materially advance patient-centred care and improve clinical and patient-reported outcomes (including quality of life) for frail older people living with CKD. TRIAL REGISTRATION: ClinicalTrials.gov NCT04538157. Registered on 3 September 2020.


Subject(s)
Frailty , Renal Insufficiency, Chronic , Aged , Humans , Middle Aged , Frail Elderly , Frailty/diagnosis , Frailty/therapy , Goals , Geriatric Assessment , Quality of Life , Australia , Renal Insufficiency, Chronic/diagnosis , Renal Insufficiency, Chronic/therapy , Randomized Controlled Trials as Topic , Multicenter Studies as Topic
2.
J Dev Orig Health Dis ; 10(2): 206-213, 2019 04.
Article in English | MEDLINE | ID: mdl-30451146

ABSTRACT

The objective of this study was to investigate the impact of the most commonly cited factors that may have influenced infants' gut microbiota profiles at one year of age: mode of delivery, breastfeeding duration and antibiotic exposure. Barcoded V3/V4 amplicons of bacterial 16S-rRNA gene were prepared from the stool samples of 52 healthy 1-year-old Australian children and sequenced using the Illumina MiSeq platform. Following the quality checks, the data were processed using the Quantitative Insights Into Microbial Ecology pipeline and analysed using the Calypso package for microbiome data analysis. The stool microbiota profiles of children still breastfed were significantly different from that of children weaned earlier (P<0.05), independent of the age of solid food introduction. Among children still breastfed, Veillonella spp. abundance was higher. Children no longer breastfed possessed a more 'mature' microbiota, with notable increases of Firmicutes. The microbiota profiles of the children could not be differentiated by delivery mode or antibiotic exposure. Further analysis based on children's feeding patterns found children who were breastfed alongside solid food had significantly different microbiota profiles compared to that of children who were receiving both breastmilk and formula milk alongside solid food. This study provided evidence that breastfeeding continues to influence gut microbial community even at late infancy when these children are also consuming table foods. At this age, any impacts from mode of delivery or antibiotic exposure did not appear to be discernible imprints on the microbial community profiles of these healthy children.


Subject(s)
Breast Feeding , Gastrointestinal Microbiome/physiology , Anti-Bacterial Agents/administration & dosage , Australia , Cohort Studies , DNA, Bacterial/isolation & purification , Feces/microbiology , Female , Firmicutes/genetics , Firmicutes/isolation & purification , Gastrointestinal Microbiome/drug effects , Healthy Volunteers , Humans , Infant , Male , Milk, Human , RNA, Ribosomal, 16S/genetics , Time Factors , Veillonella/genetics , Veillonella/isolation & purification
3.
J Hosp Infect ; 99(3): 303-305, 2018 Jul.
Article in English | MEDLINE | ID: mdl-29551649

ABSTRACT

Aerosol and splatter produced during dental treatments (ultrasonic scaling and professional mechanical tooth cleaning) are potential sources of infection. Contamination patterns on the mask, goggles, chest and gowned right arm of operators, and on the goggles of patients before and after dental treatments were investigated using ATP bioluminescence analysis. Contamination on every surface tested increased significantly after dental treatment. Maximum contamination was found on the goggles of patients. Aerosol and splatter produced during dental treatments therefore have the potential to spread infection to operators and patients. ATP bioluminescence is a useful tool for monitoring surface contamination.


Subject(s)
Adenosine Triphosphate/analysis , Aerosols , Dental Scaling , Environmental Microbiology , Luminescent Measurements , Staining and Labeling/methods , Humans
4.
J Hosp Infect ; 94(4): 393-396, 2016 Dec.
Article in English | MEDLINE | ID: mdl-27597265

ABSTRACT

Bacterial contamination of dental unit waterlines (DUWLs) was evaluated using ATP bioluminescence analysis and a conventional culture method. Water samples (N=44) from DUWLs were investigated for heterotrophic bacteria by culture on R2A agar, which gave counts ranging from 1.4×103 to 2.7×105 cfu/mL. The ATP bioluminescence results for DUWL samples ranged from 6 to 1189 relative light units and could be obtained within 1min; these correlated well with the culture results (r=0.727-0.855). We conclude that the results of the ATP bioluminescence assay accurately reflect the results of conventional culture-based testing. This method is potentially useful for rapid and simple monitoring of DUWL bacterial contamination.


Subject(s)
Adenosine Triphosphate/analysis , Bacteria/isolation & purification , Dental Offices , Disinfection/methods , Water Microbiology , Bacteria/metabolism , Colony Count, Microbial , Humans , Luminescent Measurements
5.
Cell Death Dis ; 6: e1706, 2015 Mar 26.
Article in English | MEDLINE | ID: mdl-25811803

ABSTRACT

Ku70 (Lupus Ku autoantigen p70) is essential in nonhomologous end joining DNA double-strand break repair, and ku70(-/-) mice age prematurely because of increased genomic instability and DNA damage responses. Previously, we found that Ku70 also inhibits Bax, a key mediator of apoptosis. We hypothesized that Bax-mediated apoptosis would be enhanced in the absence of Ku70 and contribute to premature death observed in ku70(-/-) mice. Here, we show that ku70(-/-) bax(+/-) and ku70(-/-) bax(-/-) mice have better survival, especially in females, than ku70(-/-) mice, even though Bax deficiency did not decrease the incidence of lymphoma observed in a Ku70-null background. Moreover, we found that ku70(-/-) mice develop lung diseases, like emphysema and pulmonary arterial (PA) occlusion, by 3 months of age. These lung abnormalities can trigger secondary health problems such as heart failure that may account for the poor survival of ku70(-/-) mice. Importantly, Bax deficiency appeared to delay the development of emphysema. This study suggests that enhanced Bax activity exacerbates the negative impact of Ku70 deletion. Furthermore, the underlying mechanisms of emphysema and pulmonary hypertension due to PA occlusion are not well understood, and therefore ku70(-/-) and Bax-deficient ku70(-/-) mice may be useful models to study these diseases.


Subject(s)
Antigens, Nuclear/genetics , DNA-Binding Proteins/genetics , Lung Diseases/genetics , Lymphoma/genetics , bcl-2-Associated X Protein/genetics , Animals , Apoptosis/genetics , Disease Models, Animal , Female , Heart Diseases/genetics , Heart Diseases/pathology , Humans , Ku Autoantigen , Lung Diseases/pathology , Lymphoma/pathology , Mice , Mice, Knockout
6.
Kyobu Geka ; 65(5): 393-6, 2012 May.
Article in Japanese | MEDLINE | ID: mdl-22569498

ABSTRACT

There are few case reports of cardiovascular surgery with multiple myeloma. We report 3 cases of cardiovascular surgery with multiple myeloma. CASE 1: A 73-year-old male hemodialytic patient with multiple myeloma was performed off-pump coronary artery bypass grafting (OPCAB) for angina. He was dead on the 72th postoperative day because of sepsis. CASE 2: A 68-year-old female patient with multiple myeloma was performed mitral valve replacement for mitral regurgitation. The postoperative course was uneventful. CASE 3: A 78-year-old male patient, the aorta was replaced with a artificial graft for impending rupture of thoracoabdominal aortic aneurysm. He was diagnosed with multiple myeloma after surgery. He was dead on the 99th postoperative day because of sepsis. One of the affecting prognosis factors is infection and it is intractable.


Subject(s)
Cardiovascular Surgical Procedures , Multiple Myeloma/complications , Aged , Angina Pectoris/surgery , Aorta/surgery , Aortic Rupture/surgery , Coronary Artery Bypass, Off-Pump , Female , Humans , Male , Mitral Valve/surgery , Mitral Valve Insufficiency/surgery , Treatment Outcome
7.
Transplant Proc ; 44(2): 409-11, 2012 Mar.
Article in English | MEDLINE | ID: mdl-22410029

ABSTRACT

Tumor vascular invasion is one of the worst factors of metastasis and/or recurrence in hepatocellular carcinoma (HCC) patients after living donor liver transplantation (LDLT), leading to poor outcomes. We investigated the relevance between preoperative parameters and histological vascular invasion among HCC patients who underwent LDLT. We enrolled 27 HCC patients who underwent LDLT from September 2003 to February 2011 in our hospital. Their primary diseases were hepatitis C (n=16) hepatitis B (n=9), primary biliary cirrhosis (n=1), and cryptogenic liver cirrhosis (n=1). The 2 groups were positive (N=7) versus negative (N=20) histological vascular invasion. We compared the greatest size and numbers of tumors from preoperative enhanced computerized axial tomography (CAT) scans, preoperative serum levels of alpha-fetoprotein (AFP) and protein induced by vitamin K absence or antagonist-II (PIVKA-II), as well as preoperative anticancer therapy. The preoperative greatest average diameter and numbers of tumor were 2.99 cm and 2.43, respectively, among positive patients, and 1.93 cm and 1.3, respectively, among patients with negative vascular invasion. The mean values of AFP and PIVKA-II were 3568.7 ng/mL and 2511.7 mAU/mL, respectively, among positive patients, and 812.8 ng/mL and 134.8 mAU/mL, respectively, among patients with negative vascular invasion. Five positive and 11 negative patients received preoperative anticancer therapy. Even if the tumor was within Milan criteria, namely, maximum size 3 cm and number of tumors 3, preoperative treatment may be a preoperative predictive factor for positive histological vascular invasion.


Subject(s)
Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/surgery , Liver Neoplasms/pathology , Liver Neoplasms/surgery , Liver Transplantation , Living Donors , Biomarkers/blood , Carcinoma, Hepatocellular/mortality , Female , Humans , Japan , Liver Neoplasms/mortality , Liver Transplantation/adverse effects , Liver Transplantation/mortality , Male , Middle Aged , Neoadjuvant Therapy , Neoplasm Invasiveness , Neoplasm Recurrence, Local , Predictive Value of Tests , Preoperative Care , Protein Precursors/blood , Prothrombin , Survival Analysis , Survival Rate , Time Factors , Tomography, X-Ray Computed , Treatment Outcome , Tumor Burden , alpha-Fetoproteins/analysis
8.
Transplant Proc ; 44(1): 140-3, 2012 Jan.
Article in English | MEDLINE | ID: mdl-22310599

ABSTRACT

BACKGROUND: Mizoribine (MZR) has been developed as an immunosuppressive agent in Japan, but it shows less potent immunosuppressive effects at doses up to 3 mg/kg/d. In this study, we investigated whether high-dose MZR (6 mg/kg/d) was effective for ABO-incompatible (ABO-i) living donor kidney transplantation (LKT) using treatment with anti-CD25 and anti-CD20 monoclonal antibodies without splenectomy. METHODS: Since 2007, we encountered 24 cases of ABO-i LKT using anti-CD20 and anti-CD25 monoclonal antibody without splenectomy. The pretransplant immunosuppressive regimen consisted of two doses of anti-CD20 antibody, mycophenolate mofetil (MMF), prednisolone, a calcineurin inhibitor (cyclosporine [7 mg/kg] or tacrolimus [0.2 mg/kg] and two doses of anti-CD25 antibody. Antibody removal by plasmapheresis was performed before LKT up to several times according to the antibody titer. The posttransplant regimen consisted of high-dose mizoribine (6 mg/kg/d) instead of MMF (MZR group, n = 12). RESULTS: The 1-year graft survival rates for the MZR and MMF groups were both 100%. The rejection rate in the MZR group (eight %) was not significantly higher than that in the MMF group (seventeen %) Serum creatinine level was not significantly different between the two groups. In the MZR group 6 (50%) patients developed CMV antigenemia-positivity versus 11 (92%) in the MMF group (P < .05). The number of patients who developed CMV disease was 0 in the MZR group and 1 (8%) in the MMF group. The number of patients treated with ganciclovir was 0% and 8%, respectively (not significant). CONCLUSIONS: We obtain good clinical results with high-dose MZR in ABO-i LKT using anti-CD20 and anti-CD25 antibody treatment without splenectomy.


Subject(s)
ABO Blood-Group System/immunology , Antibodies, Monoclonal, Murine-Derived/therapeutic use , Antibodies, Monoclonal/therapeutic use , Blood Group Incompatibility/immunology , Histocompatibility , Immunosuppressive Agents/therapeutic use , Kidney Transplantation , Recombinant Fusion Proteins/therapeutic use , Ribonucleosides/therapeutic use , Splenectomy , Adult , Antibodies, Monoclonal/adverse effects , Antibodies, Monoclonal, Murine-Derived/adverse effects , Antigens, CD20/immunology , Antiviral Agents/therapeutic use , Basiliximab , Biomarkers/blood , Creatinine/blood , Cytomegalovirus Infections/drug therapy , Cytomegalovirus Infections/immunology , Drug Therapy, Combination , Female , Graft Rejection/immunology , Graft Rejection/prevention & control , Graft Survival/drug effects , Humans , Immunosuppressive Agents/adverse effects , Interleukin-2 Receptor alpha Subunit/immunology , Japan , Kaplan-Meier Estimate , Kidney Transplantation/adverse effects , Kidney Transplantation/immunology , Living Donors , Male , Middle Aged , Recombinant Fusion Proteins/adverse effects , Ribonucleosides/adverse effects , Rituximab , Time Factors , Treatment Outcome , Young Adult
9.
Transplant Proc ; 43(6): 2418-20, 2011.
Article in English | MEDLINE | ID: mdl-21839281

ABSTRACT

In Japan, amyloidosis is a rare cause of renal failure and of renal transplantation. We treated a patient who underwent a renal transplantation because of chronic renal failure caused by secondary amyloidosis with a good result. The patient was a 50-year-old woman who was diagnosed with secondary amyloidosis and an amyloid kidney. She underwent living donor renal transplantation after about 7 years of hemodialysis. During the 3-year posttransplantation period, she maintained good allograft function with a serum creatinine level about 1.2 mg/dL. Because of amyloidosis is a systemic disease, amyloid kidney patients often experience fatal complications, so the indications for renal transplantation in amyloid patients are still controversial. But if the patient's general condition is good, renal transplantation can be an effective therapy for patients with kidney failure caused by amyloidosis.


Subject(s)
Amyloidosis/complications , Kidney Failure, Chronic/surgery , Kidney Transplantation , Living Donors , Female , Humans , Immunosuppressive Agents/therapeutic use , Kidney Failure, Chronic/etiology , Middle Aged , Treatment Outcome
10.
Transplant Proc ; 43(6): 2424-7, 2011.
Article in English | MEDLINE | ID: mdl-21839283

ABSTRACT

A 60-year-old male patient with an unknown cause for cirrhosis and a hepatoma underwent an ABO incompatible living donor liver transplantation (LDLT) from his son. The transplanted graft was his son's right lobe. For ABO incompatible transplantation, splenectomy was performed for desensitization. A catheter was inserted into the recipient's right hepatic artery for subsequent local immunosuppression. On the 15th postoperative day, a fusiform 15 × 10 mm aneurysm was observed in the graft right hepatic artery using ultrasonography and hepatic arteriography. At that time, the patient was also diagnosed to have an intraperitoneal abscess at the bottom of his left diaphragm. Administering antibiotics, we tried to embolize the aneurysm because of fear of rupture, but this manever failed because it was difficult to insert the wire in to the aneurysm to produce a stenosis around its proximal neck. However, because the aneurysm was not detectable on the 37th postoperative day, it was assumed to have embolized spontaneously. This relatively rare case revealed a hepatic artery aneurysm that spontaneously regressed after ABO incompatible LDLT.


Subject(s)
ABO Blood-Group System/immunology , Aneurysm/etiology , Blood Group Incompatibility/complications , Hepatic Artery , Histocompatibility , Liver Transplantation/adverse effects , Aneurysm/diagnosis , Blood Group Incompatibility/immunology , Hepatic Artery/diagnostic imaging , Humans , Liver Transplantation/immunology , Living Donors , Male , Middle Aged , Remission, Spontaneous , Time Factors , Tomography, X-Ray Computed , Ultrasonography
11.
Transplant Proc ; 43(6): 2379-82, 2011.
Article in English | MEDLINE | ID: mdl-21839272

ABSTRACT

BACKGROUND: Due to the shortage of deceased donors, we have expanded the indications for living-donor kidney transplantation (LKT) to include ABO-incompatible (ABO-i) individuals. However, which patients with high-titer anti-blood-group antibody can be transplanted successfully is unclear. METHODS: Since 2009 we have performed 2 high-titer ABO-i spousal LKT using anti-CD20 and anti-CD25 monoclonal antibody without splenectomy. In both cases, anti-type A antibody was 2048-fold before antibody removal. The immunosuppressive regimen consisted of 2 doses of anti-CD20 antibody (200 mg/body, day -14 to day -7), mycophenolate mofetil (1000 mg), prednisolone (10 mg starting from day -14), calcineurin inhibitor (cyclosporine [7 mg/kg] or tacrolimus [0.2 mg/kg] starting from day -7), and 2 doses of anti-CD25 antibody (20 mg/body, days 0 and 4). Antibody removal by plasmapheresis was performed up to 4 times before LKT according to the antibody titer. The posttransplantation regimen consisted of mycophenolate mofetil or mizoribine as antimetabolite. A protocol biopsy was performed at 1 month and 1 year after LKT. RESULT: The 60- and 62-year-old men had renal graft transplantation performed in the right hemipelvis without complication. After LKT, urinary output and serum creatinine decrease were within acceptable ranges without evidence of an acute rejection episode for 12 and 7 months, respectively. Patient and graft survival rates were 100%. A protocol biopsy at 1 month after LKT showed additional treatment to be unnecessary. Serious viral infection was not seen, even in the 1 patient who temporarily experienced positive changes in cytomegalovirus antigenemia. CONCLUSIONS: We obtained good clinical results among 2 high-titer ABO-i LKT using anti-CD20 and anti-CD25 antibodies without splenectomy, in conjunction with a calcineurin inhibitor plus mycophenolate mofetil or mizoribine.


Subject(s)
ABO Blood-Group System/immunology , Antibodies, Monoclonal/therapeutic use , Antigens, CD20/immunology , Blood Group Incompatibility/immunology , Histocompatibility , Immunosuppressive Agents/therapeutic use , Interleukin-2 Receptor alpha Subunit/immunology , Kidney Transplantation/immunology , Blood Group Incompatibility/diagnosis , Blood Grouping and Crossmatching , Drug Therapy, Combination , Graft Survival , Humans , Living Donors , Male , Middle Aged , Plasmapheresis , Splenectomy , Time Factors , Treatment Outcome
12.
Kyobu Geka ; 62(13): 1178-81, 2009 Dec.
Article in Japanese | MEDLINE | ID: mdl-19999099

ABSTRACT

An 81-year-old woman was referred to our hospital for surgical treatment for mitral valve regurgitation, tricuspid valve regurgitation and atrial fibrillatory bradycardia. The platelet count on admission was 4.9 x 10(4)/microl. and the results of other studies were compatible with idiopathic thrombocytopenic purpura. Although we performed high-dose transvenous immunoglobulin infusion (400 mg/kg/day) for 5 consecutive days, the platelet count showed no remarkable change. Because of progression of heart failure, we underwent cardiac operation under thrombocytopenic condition. Intra and post-operative platelet transfusion might contribute to postoperative course uneventful without bleeding tendency. In this case, high-dose immunoglobulin therapy was not effective. However the operative course was satisfactory with adequate surgical hemostasis and platelet transfusion.


Subject(s)
Heart Valve Prosthesis , Pacemaker, Artificial , Prosthesis Implantation , Purpura, Thrombocytopenic, Idiopathic/complications , Aged, 80 and over , Atrial Fibrillation/surgery , Female , Humans , Immunoglobulins, Intravenous/therapeutic use , Mitral Valve Insufficiency/surgery , Purpura, Thrombocytopenic, Idiopathic/drug therapy , Tricuspid Valve Insufficiency/surgery
13.
Sex Dev ; 3(4): 225-32, 2009.
Article in English | MEDLINE | ID: mdl-19752602

ABSTRACT

Exogenous factors such as temperature, social behavior, and salinity play a crucial role during the critical sensitive period of sex differentiation in many vertebrates. In fishes, amphibians, and reptiles temperature treatment is known to induce all-male (or female) individuals, and genes related to sex differentiation have been studied. The Japanese pufferfish, Takifugu rubripes, possesses the most compact genome among vertebrates and has immense potential for studies focusing on comparative genome analysis. In this study, we describe gonadal morphology and vasa (germ cell marker) and dmrt1 (Sertoli cell marker) expression on a molecular level in relation to the development of temperature-treated pufferfish. To investigate the relationship between temperature and gonadal development, pufferfish were exposed to high-temperature conditions (32 degrees C) during early gonadal development. Morphological observations showed that this high-temperature treatment did not influence sexual differentiation as determined by ovarian cavity characteristics; however, high-temperature treatment induces gonadal degeneration that is devoid of germ cells. RT-PCR results revealed no vasa expression within germ cell-degenerated gonads. In situ hybridization results showed that dmrt1 was expressed in somatic cells of germ cell-degenerated ovaries. These results suggest that high-temperature treatment during early gonadal development induces germ cell degeneration and masculinization of ovarian somatic cells in pufferfish.


Subject(s)
Germ Cells/cytology , Takifugu/growth & development , Temperature , Animals , Body Weight , Cell Death , DEAD-box RNA Helicases/genetics , DEAD-box RNA Helicases/metabolism , Female , Gene Expression Regulation, Developmental , Germ Cells/enzymology , Gonads/cytology , Gonads/enzymology , Gonads/growth & development , In Situ Hybridization , Male , Transcription Factors/genetics , Transcription Factors/metabolism
14.
Kyobu Geka ; 62(5): 391-4, 2009 May.
Article in Japanese | MEDLINE | ID: mdl-19425381

ABSTRACT

A 58-year-old man with a complaint of a feeling of fullness and constipation was admitted to our hospital. Enhanced computed tomography (CT) images demonstrated sacral aneurysm with multiple penetrating atherosclerotic ulcer (PAU) at the abdominal aorta above the renal artery. The aneurysm was expanded for 2 weeks progressively. An urgent thracoabdominal aorta replacement was performed. Pathological findings showed that the media of aorta was destroyed and dissected, and intramural hematoma was found. The postoperative course was good. He has been from any aortic events 12 months after surgery.


Subject(s)
Aorta, Abdominal/surgery , Aorta, Thoracic/surgery , Aortic Diseases/surgery , Atherosclerosis/surgery , Ulcer/surgery , Humans , Male , Middle Aged
15.
Article in English | MEDLINE | ID: mdl-19275683

ABSTRACT

Peroxisome proliferator activator-receptor (PPAR)-gamma is a ligand-activated transcriptional factor belonging to a steroid receptor superfamily. PPAR-gamma plays a role in both adipocyte differentiation and carcinogenesis. Up-date, PPAR-gamma is expressed in various cancer tissues, and PPAR-gamma ligand induces growth arrest of these cancer cells. In this study, we examined the expression of PPAR-gamma in human urological cancer (including renal cell carcinoma, bladder tumor, prostate cancer and testicular cancer) by RT-PCR and immunohistochemistry, and we also examined the effect of PPAR-gamma ligand in these cells by MTT assay, flow cytometry and hoechest staining. PPAR-gamma expression was significantly more extensive and intense in malignant tissues than in normal tissues. PPAR-gamma ligand induced the reduction of malignant cell viability through early apoptosis. These results demonstrated that generated PPAR-gamma in urological cancer cells may play an important role in carcinogensis and become a new target therapy in the treatment of urological cancer.


Subject(s)
PPAR gamma/physiology , Urologic Neoplasms/etiology , Carcinoma, Renal Cell/drug therapy , Carcinoma, Renal Cell/etiology , Humans , Kidney Neoplasms/drug therapy , Kidney Neoplasms/etiology , Male , PPAR gamma/drug effects , Prostatic Neoplasms/drug therapy , Prostatic Neoplasms/etiology , Testicular Neoplasms/drug therapy , Testicular Neoplasms/etiology , Urinary Bladder Neoplasms/drug therapy , Urinary Bladder Neoplasms/etiology , Urologic Neoplasms/drug therapy
16.
Transplant Proc ; 41(1): 73-5, 2009.
Article in English | MEDLINE | ID: mdl-19249480

ABSTRACT

The pathogenesis of ischemia-reperfusion (I/R) injury is known to involve cytokines and particularly surface adhesion molecules, the expression of which initiates the attachment of inflammatory cells. Renal I/R injury, a clinically important problem, is an invariable consequence of renal transplantation. The problem begins at the onset of acute tubular necrosis (ATN), when the transplantation includes a long ischemic interval or by use of a cardiac arrest donor's kidney. The cysteinyl leukotriene-1 (CysLT(1)), a potent lipid mediator in allergic disease, acts through the CysLT(1)R receptor. We researched the expression of CysLT(1)R in rat renal I/R injury as well as correlations with the degree of ATN. The right kidney was harvested and the left renal artery and vein were clamped at laparotomy. The kidney was reperfused after 90 minutes of ischemia; rats were sacrificed at 0, 3, 5, 12, and 24 hours after reperfusion. CysLT(1)R expression was analyzed by immunohistochemistry. CysLT(1)R expression was observed only in endothelial cells of a normal kidney. CysLT(1)R expression was most intense on endothelial cells at 3 hours after reperfusion, and CysLT(1)R expression on endothelial cells gradually became weaker. Twelve hours after reperfusion, ATN extended throughout the ischemic kidney. Renal I/R injury gradually progressed at time after reperfusion. Several hours after the maximal CysLT(1)R expression, we observed the maximum renal I/R injury.


Subject(s)
Kidney Tubules/pathology , Receptors, Leukotriene/physiology , Renal Artery/physiopathology , Renal Circulation/physiology , Reperfusion Injury/physiopathology , Animals , Immunohistochemistry , Kinetics , Male , Necrosis , Rats , Rats, Inbred Lew , Receptors, Leukotriene/metabolism , Renal Veins/physiopathology
17.
Transplant Proc ; 40(7): 2149-51, 2008 Sep.
Article in English | MEDLINE | ID: mdl-18790177

ABSTRACT

Renal ischemia-reperfusion (I/R) injury is a major cause of renal transplant dysfunction. Recent studies of I/R injury have focused on the function of neutrophils, the mechanisms of action of inflammatory cytokines, and oxygen free radicals, as well as other mediators. However, few reports address the cysteinyl leukotriene-1 receptor (CysLT1R), an important mediator of bronchial asthma in human beings. We examined the expression of CysLT1R in rat renal I/R injury. At laparotomy, the right kidney was harvested and the left renal artery and vein were clamped. The kidney was reperfused after 90 minutes of ischemia, and the rats were killed after 0, 3, 5, 12, or 24 hours. Expression of CysLT1R analyzed at immunohistochemistry was observed only in endothelial cells in nonischemic kidney. At 0 to 3 hours after reperfusion, CysLT1R expression on endothelial cells gradually became stronger, being most intense at 3 hours after reperfusion. Twelve hours after reperfusion, necrosis extended throughout the ischemic kidney; nearly all of the tubular epithelial cells were destroyed. At 3 to 12 hours after reperfusion, CysLT1R expression gradually became weaker on endothelial cells. At 24 hours after reperfusion, CysLT1R expression was almost at the level of that in nonischemic kidney. Expression of CysLT1R was noted in a rat model of renal I/R injury. Several hours after the maximal CysLT1R expression, we observed the maximum renal I/R injury. These results may suggest a relationship between the CysLT1R and renal I/R injury.


Subject(s)
Kidney Tubular Necrosis, Acute/metabolism , Kidney/metabolism , Receptors, Leukotriene/metabolism , Reperfusion Injury/metabolism , Animals , Immunohistochemistry , Kidney/pathology , Kidney Tubular Necrosis, Acute/pathology , Male , Rats , Rats, Inbred Lew , Renal Circulation
18.
Sex Dev ; 1(5): 311-22, 2007.
Article in English | MEDLINE | ID: mdl-18391543

ABSTRACT

In order to assess the involvement of aromatase CYP19 isoforms and endogenous sex steroids in gonadal sex differentiation and development of the Japanese fugu (Takifugu rubripes), an aromatase inhibitor (AI, fadrozole) was administered to developing fishes from the 'first feeding' till the 100th day after hatching. It was observed that ovarian cavity formation was inhibited by fadrozole at doses of 500 and 1000 microg/g diet, which was followed by testicular differentiation in all treated fugu. In the non-treated fugu, CYP19A was predominantly expressed in the ovary and CYP19B in the brain (in both sexes), although both were expressed interchangeably at low levels. An exceptionally high expression of CYP19B was also evident in testis throughout the study period. Both forms of CYP19 mRNA showed low levels of expression in brain and gonad with no significant differences between the two AI treatments. AI treatment inhibited CYP19A mRNA in trunk during the crucial period of ovarian cavity formation and CYP19B in gonad and brain by the end of gonadal sex differentiation. An elevation of testosterone and 11-ketotestosterone was observed which can be associated with the down-regulation of the circulating 17beta-estradiol production during the AI treatment period. After stopping AI treatment, both circulating estrogen and androgen were normalized. The current results suggest that suppression of CYP19A before and during morphological sex differentiation inhibits ovarian cavity formation in fugu. Furthermore, non-detectable limits of 17beta-estradiol and high testosterone levels by the end of the gonadal differentiation period can be ascribed to inhibition of CYP19B, suggesting that conversion of 17beta-estradiol from testosterone is plausibly regulated by CYP19B, and that this factor (CYP19B) may play an important role in AI-induced testicular development after gonadal sex differentiation through regulation of the testosterone-17beta-estradiol balance in fugu.


Subject(s)
Aromatase Inhibitors/pharmacology , Aromatase/physiology , Sex Differentiation/physiology , Takifugu/growth & development , Testis/growth & development , Animals , Aromatase/genetics , Brain/enzymology , Estradiol/blood , Fadrozole/pharmacology , Female , Male , Molecular Sequence Data , Ovary/anatomy & histology , Ovary/enzymology , Ovary/growth & development , RNA, Messenger , Sex Differentiation/drug effects , Takifugu/anatomy & histology , Testis/anatomy & histology , Testis/enzymology , Testosterone/blood , Time Factors
19.
J Cardiovasc Surg (Torino) ; 47(6): 659-65, 2006 Dec.
Article in English | MEDLINE | ID: mdl-17043612

ABSTRACT

AIM: The present study was designed to identify risk factors that may induce adverse outcome defined as permanent neurological dysfunction and mortality after aortic arch surgery using selective cerebral perfusion by logistic regression analysis and to reveal the role of open stent-graft placement. METHODS: One hundred and nineteen consecutive patients underwent ascending aorta and/or aortic arch operation with open technique between 1995 and 2005 were examined. Ascending aorta and/or hemiarch was replaced in 28 patients, total arch in 75 patients, and proximal or distal aortic arch replacement in 16 patients. Open stent-graft placement was used in 25 patients. RESULTS: The in-hospital mortality rate was 9.2%. Permanent neurological dysfunction occurred in 10 patients (8.4%). Thoracotomy (P=0.0331) and cardiopulmonary bypass time (P=0.0238) were significant risk factors for permanent neurological dysfunction. Preoperative shock (P=0.0266) was significant independent risk factor for mortality. Emergent operation (P=0.0454), thoracotomy (P=0.0232), and cardiopulmonary bypass time (P=0.0379) were significant independent risk factors for adverse outcome. The duration of selective cerebral perfusion was not associated with adverse outcome. Open stent-graft placement has no need of thoracotomy for aneurysm extending descending thoracic aorta and time variables concerning the operation were significantly shorter in the patients with open stent-graft placement than in patients with standard operation for total arch replacement. RESULTS: Thoracotomy was significant risk factor for adverse outcome after aortic arch repair using selective cerebral perfusion. Total arch replacement with open stent-graft placement can avoid the need of thoracotomy and reduce time variables concerning the operation to improve the surgical


Subject(s)
Aorta, Thoracic/surgery , Aorta/surgery , Blood Vessel Prosthesis Implantation/adverse effects , Cerebrovascular Circulation , Nervous System Diseases/etiology , Stents , Adult , Aged , Aged, 80 and over , Aorta/pathology , Aorta, Thoracic/diagnostic imaging , Aortic Aneurysm/diagnostic imaging , Aortic Aneurysm/mortality , Aortic Aneurysm/surgery , Aortic Aneurysm, Thoracic/diagnostic imaging , Aortic Aneurysm, Thoracic/mortality , Aortic Aneurysm, Thoracic/surgery , Blood Vessel Prosthesis Implantation/methods , Cardiopulmonary Bypass/adverse effects , Female , Humans , Logistic Models , Male , Middle Aged , Nervous System Diseases/physiopathology , Odds Ratio , Radiography , Risk Assessment , Risk Factors , Shock/complications , Thoracotomy/adverse effects , Time Factors , Treatment Outcome , Vascular Surgical Procedures
20.
Transplant Proc ; 38(7): 2199-200, 2006 Sep.
Article in English | MEDLINE | ID: mdl-16980041

ABSTRACT

Renal ischemia-reperfusion (I/R) injury during renal transplantation is a significant cause of renal dysfunction. The pathological role of free radicals in this process is a major concern. We investigated the effect of a free radical scavenger, edaravone (MCI-186), in renal I/R injury. Male Lewis rats (270 to 320 g) were used for the model. The right kidney was harvested and left renal artery and vein were clamped as laparotomy. The kidney was reperfused after 90 minutes of ischemia. Edaravone (10 mg/kg) was delivered intravenously before ischemia and after reperfusion to prevent the neutrophil activation. In the nontreatment I/R group, no rat survived beyond 4 days. However, in the edaravone I/R treatment group, one among five rats survived more than 7 days. These results suggested that treatment with edaravone ameliorated renal I/R injury, and that the agent has the potential to ameliorate preservation injury in renal transplantation.


Subject(s)
Antipyrine/analogs & derivatives , Free Radical Scavengers/therapeutic use , Renal Circulation/physiology , Reperfusion Injury/drug therapy , Animals , Antipyrine/therapeutic use , Disease Models, Animal , Edaravone , Male , Rats , Rats, Inbred Lew , Renal Circulation/drug effects , Reperfusion Injury/mortality , Reperfusion Injury/pathology , Survival Analysis
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