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1.
Transplant Proc ; 50(8): 2565-2568, 2018 Oct.
Article in English | MEDLINE | ID: mdl-30316399

ABSTRACT

Primary membranous nephropathy (MN) is an organ-specific autoimmune disease mainly caused by autoantibodies acting against the podocyte antigen M-type phospholipase A2 receptor 1 (PLA2R). Herein we present the clinical and histologic findings, including PLA2R staining, of early recurrent MN after kidney transplantation that was successfully treated with rituximab. A 60-year-old Japanese man had end-stage renal failure due to steroid-resistant primary MN and underwent ABO-incompatible living donor kidney transplantation. At 1 month after transplantation, a protocol biopsy revealed positive granular staining of IgG, C4d, and PLA2R on glomerular capillaries (GCs) without any abnormalities on light microscopy (LM). Although the patient had low-level proteinuria, recurrent MN was suspected based on the positive PLA2R staining; he was treated with an angiotensin receptor blocker and a single dose of 200 mg rituximab. However, proteinuria gradually increased to 877 mg/d. At 21 months after transplantation, a graft biopsy revealed spikes along the outer aspects of GC on LM, with stronger staining for PLA2R than that at 1 month after transplantation. A single dose of 500 mg rituximab was added, which effectively reduced proteinuria, and clinical remission continued until 3 years after transplantation. The latest graft biopsy showed reduced staining of PLA2R. The disease activity and therapeutic effect were well-reflected in the intensity of PLA2R staining. An approach intending an early diagnosis by protocol biopsy using PLA2R immunostaining is made and early treatment with rituximab will help reduce the risk of kidney graft loss due to recurrent primary MN.


Subject(s)
Glomerulonephritis, Membranous/drug therapy , Immunologic Factors/therapeutic use , Kidney Transplantation/adverse effects , Receptors, Phospholipase A2/immunology , Rituximab/therapeutic use , Autoantibodies/immunology , Early Diagnosis , Glomerulonephritis, Membranous/diagnosis , Humans , Male , Middle Aged
2.
Transplant Proc ; 49(5): 1183-1186, 2017 Jun.
Article in English | MEDLINE | ID: mdl-28583552

ABSTRACT

BACKGROUND: Sarcoidosis is a chronic systemic disease that is characterized by the formation of noncaseating granuloma and whose etiology is unclear. It is unclear whether patients with sarcoidosis are suitable organ donors. CASE: We treated a 56-year-old woman with pulmonary sarcoidosis who donated her kidney. She was previously in good health and was diagnosed with pulmonary sarcoidosis during her preoperative examination. Because she presented with no symptoms and was otherwise in good condition, donor nephrectomy was performed. RESULTS: Baseline biopsy examination showed no evidence of sarcoidosis. One year after transplantation, both the donor and the recipient had not developed kidney dysfunction or recurrence of sarcoidosis. CONCLUSION: This is a rare case in which a patient with pulmonary sarcoidosis donated a kidney for transplantation, and both the recipient and the donor were clinically healthy. A patient with sarcoidosis and no kidney lesion can donate a living kidney, because transplantation appears to be safe for both the recipient and the donor.


Subject(s)
Kidney Transplantation , Living Donors , Sarcoidosis, Pulmonary , Female , Humans , Middle Aged
3.
Eur J Surg Oncol ; 43(6): 1068-1075, 2017 Jun.
Article in English | MEDLINE | ID: mdl-28427822

ABSTRACT

OBJECTIVE: The principal objective of this study is to clarify the prognostic significance of borderline resectable pancreatic cancer (BRPC). The second objective is to evaluate the prognostic impact of the depth of pathological venous invasion. METHODS: The study included 122 pancreatic cancer patients who underwent curative surgery. All computed tomography scans of the patients were retrospectively interpreted and classified according to the NCCN guidelines, version 1.2016, as resectable (-) or borderline resectable (+) in each arterial (BR-A) and venous (BR-PV) involvement. RESULTS: The overall survival (OS) rate was significantly higher in BR-A(-) patients (n = 94) than in BR-A(+) patients (n = 28) (P = 0.001), whereas there was no difference between BR-PV(-) (n = 101) and BR-PV(+) patients (n = 21) (P = 0.257). In a multivariate analysis, the independent predictors of OS included BR-A(+) (P = 0.002), lymph node metastasis (P = 0.008), pathological venous invasion (P = 0.003), and adjuvant chemotherapy (P = 0.001). Of 39 patients who underwent venous resection, no significant difference was observed between BR-PV(-) (n = 20) and BR-PV(+) patients (n = 19) in resection rate, lymph node metastasis, the presence of extrapancreatic nerve invasion, recurrence rate, frequency of initial recurrence at a liver or local site, and OS. Pathological venous invasion was significantly deeper in BR-PV(+) patients. However, the depth of invasion was not associated with OS. CONCLUSION: The definition of venous involvement in the current guidelines predicted the depth of pathological venous invasion but not OS in BRPC patients. Further prospective, randomized studies are needed to establish treatment strategies for BRPC patients with isolated venous involvement.


Subject(s)
Adenocarcinoma/pathology , Mesenteric Veins/pathology , Pancreatectomy/methods , Pancreatic Neoplasms/pathology , Portal Vein/pathology , Adenocarcinoma/diagnostic imaging , Adenocarcinoma/surgery , Adult , Aged , Aged, 80 and over , Chemotherapy, Adjuvant , Female , Humans , Lymph Nodes/pathology , Male , Mesenteric Veins/diagnostic imaging , Mesenteric Veins/surgery , Middle Aged , Multivariate Analysis , Neoadjuvant Therapy , Neoplasm Invasiveness , Pancreatic Neoplasms/diagnostic imaging , Pancreatic Neoplasms/surgery , Pancreaticoduodenectomy , Peripheral Nerves/pathology , Portal Vein/diagnostic imaging , Portal Vein/surgery , Prognosis , Retrospective Studies , Survival Rate , Tomography, X-Ray Computed , Tumor Burden
4.
Transplant Proc ; 48(3): 734-7, 2016 Apr.
Article in English | MEDLINE | ID: mdl-27234724

ABSTRACT

BACKGROUND: An equation for the estimated glomerular filtration rate (eGFR) is generally used for evaluating renal function in Japan. OBJECTIVE: To assess the accuracy of the preoperative eGFR for estimating kidney donors' measured glomerular filtration rate (mGFR). METHODS: Between April 2009 and August 2014, 91 Japanese living kidney donors were included in this study. The eGFR was calculated as follows: eGFR = 194 × serum creatinine(-1.094) × Age(-0.287) (and × 0.739 for women), and the mGFR was evaluated using inulin clearance. The preoperative eGFR was then compared with the mGFR. RESULTS: Patients included 27 men and 64 women with a mean age of 56.8 ± 9.5 years (range, 36-79 years), mean body surface area of 1.56 ± 0.14 m(2) (range 1.27-1.92 m(2)), mean body mass index of 22.3 ± 2.3 kg/m(2) (range 14.0-27.0 kg/m(2)), and mean serum creatinine level of 0.66 ± 0.14 mg/dL (range 0.39-0.97 mg/dL). The mean eGFR was 81.3 ± 14.2 mL/min/1.73 m(2) (range 45.5-125.9 mL/min/1.73 m(2)), and the mean mGFR was 89.0 ± 15.5 mL/min/1.73 m(2) (range 45.4-130.7 mL/min/1.73 m(2)). The eGFR was significantly lower than the mGFR (P < .001). The correlation coefficient for the relationship between the eGFR and mGFR values was 0.503, and the mean difference between the 2 values was -7.8 (8.7%). CONCLUSIONS: Although the eGFR correlated with the mGFR, the eGFR values did not accurately estimate the mGFR in living kidney donors. Therefore, it is necessary to evaluate the mGFR, especially in marginal kidney donors.


Subject(s)
Glomerular Filtration Rate , Kidney Transplantation , Living Donors , Adult , Aged , Creatinine/blood , Female , Humans , Japan , Male , Middle Aged , Preoperative Care
5.
Transplant Proc ; 48(3): 827-30, 2016 Apr.
Article in English | MEDLINE | ID: mdl-27234745

ABSTRACT

BACKGROUND: Studies have revealed that patients who undergo preemptive kidney transplantation (PKT) have favorable prognoses compared with those who undergo kidney transplantation after the initiation of dialysis. The number of PKT cases performed worldwide has been increasing. The goal of this study was to determine the clinical characteristics of patients who may successfully receive PKT. METHODS: A single-center, case-control study was conducted to determine the clinical factors that lead to referral for PKT. RESULTS: Between April 1, 2009, and August 1, 2015, a total of 118 patients underwent living donor kidney transplantation. Thirty of these patients had not undergone dialysis before their initial visit to the study hospital. Of these, 20 received kidney transplantation before and after dialysis initiation, respectively (group PKT+, successful PKT; group PKT-, failed PKT). The baseline characteristics at the primary visit were compared between groups. The median duration from the first visit to the study institution to PKT was 5.6 ± 0.7 months. Serum creatinine (Cr) levels differed significantly between groups (PKT+ vs PKT-, 6.0 ± 0.3 mg/dL vs 7.5 ± 0.5 mg/dL; P = .03). The receiver-operating characteristic curves revealed that a serum Cr level >5.7 mg/dL at the initial visit to the unit was a cutoff point for predicting the success of PKT (area under the curve, 0.721; P = .02). CONCLUSIONS: Our results indicate that PKT should be performed within ∼6 months of the initial visit to the transplant center. Serum Cr levels <5.7 mg/dL predict successful PKT.


Subject(s)
Graft Survival , Kidney Transplantation , Adult , Case-Control Studies , Creatinine/blood , Female , Humans , Living Donors , Male , Middle Aged , Prognosis , Renal Dialysis
6.
Transplant Proc ; 48(3): 940-2, 2016 Apr.
Article in English | MEDLINE | ID: mdl-27234773

ABSTRACT

OBJECTIVE: We report the clinical course and pathologic findings of a kidney transplant donor who was diagnosed with immunoglobulin A (IgA) nephropathy by means of preimplantation biopsy and was later treated with methylprednisolone and tonsillectomy. CASE REPORT: The patient was a 57-year-old woman who met the criteria for kidney donation and was accepted as a donor. Donor nephrectomy was performed, and the preimplantation biopsy revealed that the donor had IgA nephropathy. One month after the nephrectomy, the donor's laboratory findings indicated proteinuria and hematuria. Because these findings indicated active IgA nephropathy, we decided to perform tonsillectomy and methylprednisolone pulse therapy. Soon after these treatments, the patient's proteinuria and hematuria were no longer observed. CONCLUSIONS: Subclinical IgA nephropathy can be incidentally found on preimplantation biopsies of living kidney donors. As demonstrated in this case, IgA nephropathy can become exacerbated and requires therapeutic intervention after kidney donation. Informed consent and careful observation should be used before and after transplantation, even for donors who have been determined to be eligible for kidney donation.


Subject(s)
Donor Selection , Glomerulonephritis, IGA/diagnosis , Glomerulonephritis, IGA/therapy , Kidney Transplantation , Living Donors , Female , Glucocorticoids/therapeutic use , Hematuria/etiology , Hematuria/therapy , Humans , Methylprednisolone/therapeutic use , Middle Aged , Nephrectomy , Proteinuria/etiology , Proteinuria/therapy , Tonsillectomy
7.
Am J Transplant ; 16(3): 886-96, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26555133

ABSTRACT

ABO-incompatible living kidney transplantation (ABO-ILKT) has steadily become more widespread. However, the optimal immunosuppressive regimen for ABO-ILKT remains uncertain. We aimed to determine the longitudinal changes in the outcomes from ABO-ILKT compared with those from ABO-compatible living kidney transplantation (ABO-CLKT) over the last 25 years. Of 1195 patients who underwent living kidney transplantations (LKT) at our institute between 1989 and 2013, 1032-including 247 ABO-ILKT and 785 ABO-CLKT cases-were evaluated for graft survival, patient survival, infectious adverse events, and renal function. The patients were divided into four groups according to the transplantation era and ABO-compatibility. In the past decade, ABO-ILKT and ABO-CLKT recipients yielded almost equivalent outcomes with respect to the 9-year graft survival rates, which were 86.9% and 92.0%, respectively (hazard ratio [HR] 1.38, 95% confidence interval [CI] 0.59-3.22, p = 0.455). The graft survival rate for ABO-ILKT conducted between 2005 and 2013 was better than that for ABO-ILKT conducted between 1998 and 2004 (HR 0.30, 95% CI 0.13-0.72, p = 0.007). ABO-ILKT recipients showed substantial improvements in the graft survival rate over time. Graft survival was almost identical over the past decade, regardless of ABO-incompatibility. Currently, ABO-ILKT is an acceptable treatment for patients with end-stage renal disease.


Subject(s)
ABO Blood-Group System/immunology , Blood Group Incompatibility/immunology , Desensitization, Immunologic/methods , Kidney Failure, Chronic/surgery , Kidney Transplantation , Adult , Female , Follow-Up Studies , Glomerular Filtration Rate , Graft Survival , Humans , Immunosuppressive Agents/therapeutic use , Kidney Function Tests , Living Donors , Male , Middle Aged , Prognosis , Prospective Studies , Retrospective Studies , Risk Factors
8.
Transplant Proc ; 47(8): 2533-6, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26518965

ABSTRACT

OBJECTIVE: We report a case of the clinical course and pathologic findings for a kidney transplant recipient with plasma cell-rich rejection (PCRR) accompanied by antibody-mediated rejection (ABMR). METHODS: A 29-year-old man with end-stage renal disease caused by lupus nephritis received an ABO-compatible living kidney transplant. RESULTS: Eighteen months after transplantation, the patient presented with proteinuria and increased serum creatinine. An episode biopsy revealed severe tubulointerstitial infiltration with plasma cells accompanied by peritubular capillaritis and positive findings on immunofluorescent C4d staining. Donor-specific antibodies were positive for DR52, and the patient was subsequently diagnosed with PCRR accompanied by ABMR. Treatment was initiated with high-dose steroids, intravenous immunoglobulin, gusperimus hydrochloride, muronmonab antibody CD3, and rituximab. However, ABMR persisted and allograft failure developed 20 months after onset. CONCLUSIONS: We argue that PCRR accompanied by ABMR is a subtype of PCRR that can progress to allograft failure owing to persistent ABMR.


Subject(s)
Graft Rejection/immunology , Isoantibodies/immunology , Kidney Failure, Chronic/surgery , Kidney Transplantation/adverse effects , Plasma Cells/immunology , ABO Blood-Group System , Adult , Antibody Specificity , Biopsy , HLA-DR Serological Subtypes/immunology , Humans , Immunoglobulins, Intravenous/therapeutic use , Isoantibodies/analysis , Kidney/immunology , Kidney Transplantation/methods , Living Donors , Lupus Nephritis/complications , Male , Transplant Recipients , Transplantation, Homologous
9.
Neuroscience ; 227: 336-49, 2012 Dec 27.
Article in English | MEDLINE | ID: mdl-23069764

ABSTRACT

Yokukansan (YKS) is a traditional Japanese medicine consisting of seven medicinal herbs that is used for the treatment of neurosis, insomnia, and the behavioral/psychological symptoms of dementia. This study examined the effects of YKS on morphine tolerance and physical dependence in mice. Daily oral administration of YKS (0.5 or 1.0 g/kg) for 3 weeks significantly attenuated morphine tolerance and naloxone-precipitated morphine withdrawal signs (jumps and body weight loss) without affecting the analgesic effect of morphine. The inhibitory effect of YKS on withdrawal jumps in morphine-dependent mice was blocked by a single pretreatment with an α(2)-adrenoceptor antagonist, yohimbine, but not by an α(1)-adrenoceptor antagonist, prazosin. A similar inhibitory effect on withdrawal jumps was observed by repeated administration of yohimbine. The membrane expression of α(2A)-adrenoceptors in the pons/medulla was decreased in morphine withdrawn animals; this reduction was prevented by repeated administration of YKS or yohimbine. Competitive radioligand and [(35)S]guanosine-5'-O-(3-thiotriphosphate) binding assays revealed that YKS and its constituent herbs, Glycyrrhiza (GR) and Uncaria hook (UH), had specific binding affinity for and antagonist activity against the α(2A)-adrenoceptor. Certain chemical constituents, including GR -derived glycyrrhizin and its metabolite, 18ß-glycyrrhetinic acid, and UH-derived geissoschizine methyl ether (GME), shared such activities. Repeated administration of GR, UH, glycyrrhizin or GME significantly inhibited morphine withdrawal signs. These results suggest that YKS and its active constituents inhibit morphine tolerance and physical dependence, and that the latter is due at least in part to the prevention of the decreased membrane expression of the α(2A)-adrenoceptor in the brainstem by its prolonged blockade.


Subject(s)
Behavior, Addictive/drug therapy , Drugs, Chinese Herbal/therapeutic use , Morphine Dependence/drug therapy , Receptors, Adrenergic, alpha-2/metabolism , Adrenergic Agents/pharmacology , Adrenergic alpha-Antagonists/pharmacokinetics , Adrenergic beta-Antagonists/pharmacology , Analysis of Variance , Animals , Disease Models, Animal , Dose-Response Relationship, Drug , Drug Tolerance , Guanosine 5'-O-(3-Thiotriphosphate)/pharmacokinetics , Guanosine Diphosphate/pharmacology , Isotopes/pharmacokinetics , Male , Mice , Norepinephrine Plasma Membrane Transport Proteins/metabolism , Pain Threshold/drug effects , Propranolol/pharmacology , Protein Binding/drug effects , Radioligand Assay , Time Factors , Tropanes/pharmacokinetics
10.
Br J Cancer ; 105(9): 1331-7, 2011 Oct 25.
Article in English | MEDLINE | ID: mdl-21970881

ABSTRACT

BACKGROUND: We investigated the changes in reactive oxygen species (ROS) and angiogenesis through angiotensin II (Ang II) type 1 receptor (AT1R) after the development of acquired platinum resistance in bladder cancer. METHODS: Four invasive human bladder cancer cell lines, T24, 5637, T24PR, and 5637PR, were used in vitro, whereas in vivo, T24 and T24PR cells were used. T24PR and 5637PR cells were newly established at our institution as acquired platinum-resistant sublines by culturing in cisplatin (CDDP)-containing conditioned medium for 6 months. RESULTS: Ang II induced significantly higher vascular endothelial growth factor (VEGF) production in T24PR and 5637PR cells than in their corresponding parent cells in vitro, whereas Ang II induced a further increase in VEGF production. These platinum-resistant cells also showed significantly higher AT1R expression than their corresponding parent cells. ROS was also significantly upregulated in T24PR and 5637PR cells, whereas increased AT1R expression was significantly downregulated by scavenging free radicals. We also demonstrated the efficacy of AT1R blockade at suppressing the growth of platinum-resistant xenograft model. CONCLUSION: Our findings indicate a new molecular mechanism for upregulated AT1R signalling through increased ROS when tumours progressed after the CDDP-based regimens, and shed light on the importance of AT1R blockade for platinum-resistant bladder cancers.


Subject(s)
Cisplatin/pharmacology , Neovascularization, Pathologic , Receptor, Angiotensin, Type 1/biosynthesis , Urinary Bladder Neoplasms/blood supply , Urinary Bladder Neoplasms/metabolism , Angiotensin II/pharmacology , Angiotensin II Type 1 Receptor Blockers/pharmacology , Animals , Antipyrine/analogs & derivatives , Antipyrine/pharmacology , Cell Line, Tumor , Drug Resistance, Neoplasm , Edaravone , Humans , Mice , Mice, Nude , Reactive Oxygen Species/metabolism , Urinary Bladder Neoplasms/drug therapy , Vascular Endothelial Growth Factor A/metabolism
11.
Rev Sci Instrum ; 82(7): 076104, 2011 Jul.
Article in English | MEDLINE | ID: mdl-21806238

ABSTRACT

We have developed a laser Doppler velocimeter (LDV) for measuring velocity distributions in blood vessels. We converted a transmission-based LDV into a reflection-based LDV to make it suitable for clinical applications. The velocity distribution image of a serpentine flow channel obtained could be qualitatively explained by the numerical results. Finally, we evaluated the system by using it to measure injection of blood into a glass tube by a syringe pump. The results obtained demonstrate that erythrocytes can be used as seeding particles for the reflection-type micro multipoint LDV. The results obtained are useful as basic data for clinical applications.


Subject(s)
Blood Vessels/physiology , Laser-Doppler Flowmetry/instrumentation , Animals , Hemorheology , Male , Mice , Microcirculation , Molecular Imaging
12.
Transpl Infect Dis ; 13(3): 318-23, 2011 Jun.
Article in English | MEDLINE | ID: mdl-20804536

ABSTRACT

Cytomegalovirus (CMV) reinfection of seropositive individuals has been associated with adverse outcomes in organ transplantation and is a frequent cause of congenital infection. Previously we demonstrated that mismatching of CMV glycoprotein H (gH) serotypes was associated with CMV disease after renal transplantation. Because the antigen domain 2 (AD2) epitope of glycoprotein B (gB) is conserved among CMV isolates and is one of the known targets of neutralizing antibodies, in this study we investigated whether antibodies against the epitope contribute to protection from CMV reinfection in renal transplantation, irrespective of gH serological matching. For this purpose, the gB and gH serology and clinical outcomes were analyzed retrospectively for 77 transplant recipients in the donor positive/recipient positive setting, who were managed by preemptive strategy. We found that there was a good negative correlation between the numbers of antigenemia-positive cells and the levels of antibodies against gB AD2 in the CMV-gH antibody matched group, but not in the CMV-gH antibody mismatched group. None of the recipients with antibodies against both gB AD2 and strain-specific epitopes of gH have experienced CMV disease during 6 month after transplantation, while 28% of those who lacked either/both antibody response needed preemptive therapy. Because the outcome was statistically significant, antibodies against gB AD2 can be a useful indicator to predict emergence of CMV disease for preemptive therapy, in addition to antibodies against the mismatched gH types.


Subject(s)
Antibodies, Viral/blood , Antigens, Viral/immunology , Cytomegalovirus Infections/immunology , Epitopes/immunology , Kidney Transplantation/adverse effects , Viral Envelope Proteins/immunology , Antibodies, Viral/immunology , Antigens, Viral/chemistry , Cytomegalovirus/classification , Cytomegalovirus/immunology , Cytomegalovirus Infections/virology , Epitopes/genetics , Humans , Kidney Transplantation/immunology , Serotyping , Species Specificity , Tissue Donors , Viral Envelope Proteins/chemistry
13.
Transplant Proc ; 42(5): 1476-8, 2010 Jun.
Article in English | MEDLINE | ID: mdl-20620457

ABSTRACT

INTRODUCTION: There are few recent studies investigating increased risks for adverse effects leading to chronic kidney disease (CKD) among kidney donors. The aim of this study was to identify factors that protect renal function among actual live kidney donors. MATERIALS AND METHODS: We enrolled 68 individuals who had undergone donor nephrectomy in this study. We assessed donor age, body mass index (BMI), casual blood pressure, preoperative and 3-month follow-up serum creatinines, serum total cholesterol, and several other clinical parameters. The severity of arteriosclerosis in the arteriolar and interlobular arteries of the donor kidney was semiquantitatively evaluated in 4 grades using back table biopsies. Impairment of renal function after surgery was expressed by differences in serum creatinine levels. RESULTS: The ratio of glomerular sclerosis, systolic blood pressure, and diastolic blood pressure positively correlated with donor age. Deterioration of renal function after donor nephrectomy negatively correlated with BMI and positively correlated with severity of arteriosclerosis in interlobular arteries. A multiple regression analysis model with respect to the severity of arteriosclerosis in interlobular arteries showed significant influence, of serum creatinine and systolic blood pressure. CONCLUSIONS: Preventing progression of arteriosclerosis and selecting the optimal BMI before donor nephrectomy will help to avoid impaired renal function among live kidney donors.


Subject(s)
Living Donors , Nephrectomy/adverse effects , Adult , Aged , Arteriosclerosis/epidemiology , Arteriosclerosis/pathology , Arteriosclerosis/physiopathology , Body Mass Index , Cholesterol/blood , Creatinine/blood , Diastole/physiology , Disease Progression , Female , Humans , Male , Middle Aged , Renal Artery/pathology , Risk Factors , Uric Acid/blood
14.
Article in English | MEDLINE | ID: mdl-20036750

ABSTRACT

Emerging evidence has shown that acute heat exposure affects metabolic characteristics and causes oxidative damage to skeletal muscle in birds. Little is known, however, about such phenomena under chronic heat stress conditions. To address this, we designed the present study to determine the influence of cyclic (32 to 24 to 32 degrees C: 32 degrees C for 8 h/d, 32-24-32HS ), and constant (32 and 34 degrees C, 32HS and 34HS, respectively) heat exposure on the metabolic and peroxide status in skeletal muscle of 4-wk-old male broiler chickens. Heat stress, particularly in the 32HS and 34HS groups, depressed feed intake and growth, while cyclic high temperature gave rise to a less severe stress response in performance terms. Malondialdehyde (MDA) levels in skeletal muscle were enhanced (P<0.05) by constant heat treatment; the degree of enhancement was not as large as the changes observed in our previous 'acute' heat stress model. The 3HADH (3-hydroxyacyl CoA dehydrogenase related to fatty acid oxidation) and CS (citrate synthase) enzyme activities were lowered (P<0.05) by both the cyclic and constant 34HS treatments, and constant 34HS group, respectively. These results suggest that chronic heat exposure decreases metabolic oxidation capacity in skeletal muscle of broiler chickens. On exposure to chronic heat stress, GPx activity remained relatively constant, though a temperature-dependent elevation in Cu/Zn-SOD activity was observed, implying that anti-oxidation ability was disturbed by the chronic stress condition. From these results it can be concluded that chronic heat stress did not induce oxidative damage to a major extent. This may probably be due to a decrease in metabolic oxidation capacity or due to a self-propagating scavenging system, though the system was not fully activated.


Subject(s)
Chickens/metabolism , Heat-Shock Response , Muscle, Skeletal/metabolism , Muscle, Skeletal/pathology , Oxidative Stress , Animals , Body Temperature , Chickens/blood , Chickens/growth & development , DNA, Mitochondrial/genetics , Free Radical Scavengers/metabolism , Gene Dosage/genetics , Gene Expression Regulation , Ion Channels/genetics , Ion Channels/metabolism , Malondialdehyde/metabolism , Mitochondrial Proteins/genetics , Mitochondrial Proteins/metabolism , Oxidation-Reduction , RNA, Messenger/genetics , RNA, Messenger/metabolism , Substrate Specificity , Uncoupling Protein 1 , Weight Gain
15.
Am J Transplant ; 9(3): 567-77, 2009 Mar.
Article in English | MEDLINE | ID: mdl-19260836

ABSTRACT

The impact of acute antibody-mediated rejection (AAMR) on the long-term outcome on ABO-incompatible (ABOI) kidney transplantation is not well understood. We retrospectively analyzed the long-term impact of AAMR and risk factors for AAMR in 57 consecutive recipients performed between 1999 and 2004. Nineteen patients (33%) who developed AAMR within 3 months posttransplantation constituted of the AMR group. The graft survival rate was significantly lower in the AMR group (AMR vs. non-AMR, respectively; 5 years: 84% vs. 95%; 8 years: 45% vs. 95%; p = 0.009). The prevalence of transplant glomerulopathy at 1 year posttransplantation was significantly higher in the AMR group (AMR 64% vs. non-AMR 3%, p < 0.001). Multivariate analysis demonstrated that anti-blood group IgG antibody titers of 1:32 at the time of transplantation (OR, 9.52; p = 0.041) and donor-specific anti-HLA antibodies (DSHA) detected by Luminex single bead method (OR, 5.68; p = 0.015) were independent risk factors for AAMR regardless of baseline anti-blood group IgG antibody titers. Our results indicate that AAMR has a heavy impact on the long-term outcome and preoperative DSHA appears to have a more significant association with poor graft outcomes than anti-blood group antibodies, even in ABOI kidney transplantation.


Subject(s)
ABO Blood-Group System/immunology , Antibodies/immunology , Blood Group Incompatibility/immunology , Graft Rejection/immunology , Kidney Transplantation/immunology , Adult , Creatine/blood , Female , Follow-Up Studies , Humans , Male , Risk Factors
16.
Transplant Proc ; 40(7): 2370-2, 2008 Sep.
Article in English | MEDLINE | ID: mdl-18790237

ABSTRACT

AIM: Tacrolimus (TAC) is an effective primary immunosuppressive agent in kidney transplantation. Chronic nephrotoxicity due to TAC has been reported to be similar to that of cyclosporine in kidney transplant patients. Since, the severity and influence of chronic TAC nephrotoxicity are not fully elucidated, we studied the clinicohistological characteristics of chronic TAC nephrotoxicity in kidney transplants. PATIENTS AND METHODS: We retrospectively studied the clinicohistological profiles of 15 transplant patients under TAC-based immunosuppression, who were diagnosed as chronic TAC nephrotoxicity by allograft biopsies, showing characteristic arteriolopathy--periodic acid-Schiff PAS--positive hyaline thickening in small arteries--between January 2004 and December 2005. The mean recipient age was 37.3 years and they consisted of 11 men and 4 women. The mean age of their donors was 59.4 years. RESULTS: The diagnoses of chronic TAC nephrotoxicities were established at an average of 54.7 months postoperatively. The severities of arteriolopathy were moderate in eight cases and severe in eight cases. The mean dosage of TAC at the time of diagnoses was 0.054 mg/kg with mean whole blood trough levels of 5.09 ng/mL, which is recognized to be within the so-called recommended level. Moderate to severe arteriosclerosis of medium-sized arteries were observed in 12 cases (80.0%). CONCLUSION: The existence of moderate to severe arteriosclerosis in medium-sized arteries would have the potential of causing chronic TAC nephrotoxicities, rather than the dosage or whole blood trough level of TAC.


Subject(s)
Immunosuppressive Agents/toxicity , Kidney Transplantation/pathology , Tacrolimus/toxicity , ABO Blood-Group System , Adolescent , Adult , Arteries/pathology , Arterioles/pathology , Biopsy , Cadaver , Child , Female , Graft Rejection/epidemiology , Histocompatibility Testing , Humans , Kidney Transplantation/immunology , Living Donors , Male , Middle Aged , Retrospective Studies , Tissue Donors/statistics & numerical data , Transplantation, Homologous/immunology , Transplantation, Homologous/pathology , Treatment Failure
17.
Transplant Proc ; 40(5): 1741-3, 2008 Jun.
Article in English | MEDLINE | ID: mdl-18589183

ABSTRACT

A 58-year-old man underwent kidney transplantation on November 14, 2002 for end-stage kidney disease after Chinese herb nephropathy. Immunosuppressive therapy was maintained with tacrolimus, mycophenolate mofetil, and methylpredonisolone. He was diagnosed with right ureteral cancer and underwent right nephroureterectomy on December 13, 2003. Then, he underwent left nephroureterectomy for left ureteral cancer on March 5, 2004. Subsequently, he was diagnosed with multiple bladder cancers and carcinoma in situ. On August 31, he underwent radical cystectomy with an orthotopic ileal neobladder (Studer's method). The postoperative course was uneventful. After 3 years follow-up, this patient shows no evidence of recurrence and his serum creatinine level is stable (1.7 mg/dL). The continence is maintained during both day and night; he voids without intermittent self-catheterization. We suggest that an orthotopic ileal neobladder is a safe method of urinary diversion after cystectomy in kidney transplant recipients.


Subject(s)
Drugs, Chinese Herbal/toxicity , Kidney Transplantation , Kidney/pathology , Urinary Bladder/physiopathology , Aged , Aged, 80 and over , Creatinine/blood , Female , Humans , Hydronephrosis/chemically induced , Hydronephrosis/surgery , Male , Mothers , Tissue Donors , Ureter/surgery , Urination
18.
Am J Transplant ; 8(1): 86-94, 2008 Jan.
Article in English | MEDLINE | ID: mdl-18021283

ABSTRACT

Numerous studies have shown that protocol biopsies have predictive power. We retrospectively examined the histologic findings and C4d staining in 89 protocol biopsies from 48 ABO-incompatible (ABO-I) transplant recipients, and compared the results with those of 250 controls from 133 ABO-compatible (ABO-C) transplant recipients given equivalent maintenance immunosuppression. Others have shown that subclinical rejection (borderline and grade I) in ABO-C grafts decreased gradually after transplantation. In our study, however, subclinical rejection in the ABO-I grafts was detected in 10%, 14% and 28% at 1, 3 and 6-12 months, respectively. At 6-12 months, mild tubular atrophy was more common in the ABO-C grafts whereas the incidence of transplant glomerulopathy did not differ between the two groups (ABO-C: 7%; ABO-I: 15%; p = 0.57). In the ABO-I transplants, risk factors for transplant glomerulopathy in univariate analysis were positive panel reactivity (relative risk, 45.0; p < 0.01) and a prior history of antibody-mediated rejection (relative risk, 17.9; p = 0.01). Furthermore, C4d deposition in the peritubular capillaries was detected in 94%, with diffuse staining in 66%. This deposition, however, was not linked to antibody-mediated rejection. We conclude that, in the ABO-I kidney transplantation setting, detection of C4d alone in protocol biopsies might not have any diagnostic or therapeutic relevance.


Subject(s)
ABO Blood-Group System/immunology , Blood Group Incompatibility/pathology , Graft Rejection/pathology , Kidney Transplantation , Kidney/pathology , Adult , Biopsy , Blood Group Incompatibility/blood , Blood Group Incompatibility/immunology , Complement C4b/metabolism , Female , Graft Rejection/blood , Graft Rejection/immunology , Humans , Kidney/metabolism , Kidney Transplantation/immunology , Kidney Transplantation/pathology , Male , Middle Aged , Retrospective Studies
19.
Am J Transplant ; 7(4): 825-31, 2007 Apr.
Article in English | MEDLINE | ID: mdl-17250557

ABSTRACT

Several protocols allow the successful ABO incompatible living-related kidney transplantation (ABO-ILKT), yet no single method has emerged as the best. We have made several substantial changes to our ABO-ILKT protocol over the past decade and a half and have attempted to determine whether the changes in immunosuppressive agents have resulted in a better outcome. We used methylprednisolone (MP), cyclosporine (CsA), azathioprine (AZ), antilymphocyte globulin (ALG) and deoxyspergualine (DSG) in the 105 cases of ABO-ILKT (group 1) between 1989 and 1999, and MP, tacrolimus (FK506), mycophenolate mofetil (MMF) in the 117 cases of ABO-ILKT (group 2) between 2000 and 2004. We compared the patient and graft survival rates as well as the incidence rate of acute rejection in these two eras, when different regimens were used. There were significant differences in the 1- and 5-year graft survival rates between groups 1 and 2 (1-year: 78% in group 1 vs. 94% in group 2; 5-year: 73% in group 1 vs. 90% in group 2, p = 0.008). Also, a higher incidence rate of acute rejection was significantly observed in group 1 (50/105, 48%) than in group 2 (18/117, 15%) (p < 0.001). We conclude that the FK/MMF combination regimen provides excellent graft survival results in ABO-ILKT.


Subject(s)
ABO Blood-Group System/immunology , Blood Group Incompatibility , Immunosuppressive Agents/therapeutic use , Kidney Transplantation/immunology , Living Donors , Adult , Autoantibodies , Female , Graft Rejection/drug therapy , Graft Rejection/epidemiology , Graft Survival , Humans , Immunosuppressive Agents/administration & dosage , Kidney Transplantation/mortality , Male , Middle Aged , Postoperative Complications/immunology , Retrospective Studies , Survival Analysis
20.
Transplant Proc ; 36(7): 1917-9, 2004 Sep.
Article in English | MEDLINE | ID: mdl-15518698

ABSTRACT

INTRODUCTION: Retroperitoneoscopic live donor nephrectomy (RPLDN) was performed because it is considered to be less invasive than open live donor-nephrectomy (OLDN) or transperitoneal laparoscopic live donor nephrectomy. PATIENTS AND METHODS: Between July 2001 and May 2003, 118 consecutive live donor kidney grafts were procured using RPLDN or OLDN. The patients who underwent RPLDN were divided into 2 groups: an initial group 1 (n = 38) and a subsequent group 2 (n = 48).Thirty-two patients who underwent OLDN during the same period were used as controls (group 3). The patients were placed in the lateral position. Three retroperitoneoscopic ports were inserted. The kidneys were retrieved through a 5-cm flank incision just below the 11th rib in group 1. In group 2, a 5-cm Pfannenstiel incision was used to extract the kidney. RESULTS: The operative time was 307 +/- 88 minutes, 245 +/- 42 minutes, and 215 +/- 70 minutes in groups 1, 2, and 3, respectively (group 1 vs group 2 or 3, P < .01). The mean postoperative pentazocine (painkiller) requirements were 12 mg, 4.4 mg, and 22 mg in groups 1, 2, and 3, respectively (group 2 vs group 1 or 3, P < .01). The hospital stay was 6.6 +/- 1.6, 4.9 +/- 0.7, and 7.0 +/- 0.1 days in groups 1, 2, and 3, respectively (group 2 vs group 1 or 3, P < .01). There were no serious complication, such as massive bleeding or bowel injury. CONCLUSIONS: RPLDN may be safer and less invasive than open donor nephrectomy.


Subject(s)
Kidney Transplantation/physiology , Living Donors , Nephrectomy/methods , Humans , Japan , Retroperitoneal Space , Retrospective Studies , Tissue and Organ Harvesting/methods , Treatment Outcome
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