Elevated oxidative stress measured as albumin redox state in continuous ambulatory peritoneal dialysis patients correlates with small uraemic solutes.
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Biomarkers↗
Biomedical subjects
Masaaki Nakayama
Publications and source records attributed to Masaaki Nakayama.
Clustering of Helicobacter pylori VacA in lipid rafts, mediated by its receptor, receptor-like protein tyrosine phosphatase beta, is required for intoxication in AZ-521 Cells.
Helicobacter pylori vacuolating cytotoxin, VacA, induces multiple effects on epithelial cells through different cellular events: one involves pore formation, leading to vacuolation, mitochondrial damage, and apoptosis, and the second involves cell signaling, resulting in stimulation of proinflammatory responses and cell detachment. Our recent data demonstrated that VacA uses receptor-like protein tyrosine phosphatase beta (RPTPbeta) as a receptor, of which five residues (QTTQP) at positions 747 to 751 are involved in binding. In AZ-521 cells, which mainly express RPTPbeta, VacA, after binding to RPTPbeta in non-lipid raft microdomains on the cell surface, is localized with RPTPbeta in lipid rafts in a temperature- and VacA concentration-dependent process. Methyl-beta-cyclodextrin (MCD) did not block binding to RPTPbeta but inhibited translocation of VacA with RPTPbeta to lipid rafts and all subsequent events. On the other hand, 5-nitro-2-(3-phenylpropylamino)-benzoic acid (NPPB), which disrupts anion channels, did not inhibit translocation of VacA to lipid rafts or VacA-induced activation of p38 mitogen-activated protein (MAP) kinase, but inhibited VacA internalization followed by vacuolation. Thus, p38 MAP kinase activation did not appear to be required for internalization. In contrast, phosphatidylinositol-specific phospholipase C (PI-PLC) inhibited translocation, as well as p38 MAP kinase/ATF-2 activation, internalization, and VacA-induced vacuolation. Neither NPPB nor PI-PLC affected VacA binding to cells and to its receptor, RPTPbeta. Thus, receptor-dependent translocation of VacA to lipid rafts is critical for signaling pathways leading to p38 MAP kinase/ATF-2 activation and vacuolation.
Activating Transcription Factor 2↗
Quantitative assessment of the peritoneal vessel density and vasculopathy in CAPD patients.
BACKGROUND: Peritoneal sclerosis (PS) complicates continuous ambulatory peritoneal dialysis (CAPD). Exploring the peritoneal vascular changes, which are characteristic histological findings in long-term PD, may give new insight into the basic pathological process leading to PS. We present a quantitative analysis of peritoneal vascular density as well as vasculopathy grades in relation to PD duration. METHODS: Peritoneal samples from 56 stable CAPD patients were analysed, and cases with membrane failure were excluded. Patients were classified into four groups according to CAPD duration in years: group A (n = 12), 0 year; group B (n = 11), 1-5 years; group C (n = 17), 5-9 years; and group D (n = 16), >9 years. The total density, of microvessels (capillaries, post-capillary venules and venules) and the density of each vasculopathy grade (0 = intact, 1 = mild, 2 = moderate and 3 = severe) in the compact zone were calculated (numbers/mm(2)) in each sample and the percentage ratio of each grade in relation to the total vessel density was also determined. RESULTS: There was no significant difference in the total vessel density (P-value = 0.64). In the grade of vasculopathy (density and percentage ratio), there were significant differences among groups, with grade 0 highest in group A, grade 1 highest in group C and grade 3 highest in group D. CONCLUSION: The results of this study indicate that vascular density does not increase, at least in stable uncomplicated PD, and that intact vessels decrease with time on PD, while the severe grades of vasculopathy predominate especially on a long-term basis.
Adult↗
Helicobacter pylori vacuolating cytotoxin induces activation of the proapoptotic proteins Bax and Bak, leading to cytochrome c release and cell death, independent of vacuolation.
Helicobacter pylori vacuolating cytotoxin, VacA, which causes vacuolation of gastric epithelial cells and other types of cultured cells, is known to stimulate apoptosis via a mitochondria-dependent pathway. In the present study, we examined the mechanisms of VacA-induced mitochondrial damage. Intracellular VacA localization was monitored by immunostaining and confocal microscopy; in AZ-521 cells in which cytochrome c release was stimulated, most of VacA was localized to vacuoles rather than mitochondria. VacA reduced the membrane potential of isolated mitochondria without inducing cytochrome c release, suggesting that it did not act directly to induce cytochrome c release from mitochondria and that in intact cells, VacA-induced cytochrome c release involved apoptosis-related factor(s), such as a proapoptotic Bcl-2 family protein. In agreement, flow cyto-metric analyses using antibodies specific for activated Bax revealed that intracellular Bax was activated by VacA in a concentration- and time-dependent manner. Using active form-specific antibodies, we also observed that the Bcl-2 family protein, Bak, was activated. By confocal microscopy, Bax and Bak were activated in AZ-521 cells in which cyto-chrome c release was induced by VacA. In addition, small interfering RNA-induced silencing of the bax gene resulted in reduction of VacA-stimulated cytochrome c release, consistent with a contribution of VacA-induced Bax activation to cytochrome c release. NH4Cl enhanced both VacA-induced vacuolation and Bax activation, whereas Bax activation was not inhibited by bafilomycin A1, which inhibited vacuolation caused by VacA. These results suggest that VacA acts through different signaling pathways to induce apoptosis via Bax activation, independent of vacuolation.
Apoptosis↗
[Survey on the current status of delivered informed consent for renal replacement therapy among patients with end-stage renal disease].
We conducted a survey on the adequacy of delivered informed consent (IC) among patients with end-stage renal disease (ESRD) regarding the information provided on renal replacement therapies (RRT): Hemodialysis (HD), peritoneal dialysis (PD), and renal transplantation (RTx). A self-assessment style of questionnaire entitled "Informed consent for the selection of dialysis therapy modality" was prepared for evaluation, and the adequacy of IC was scored by 5 grades ranging from "excellent" to "bad". The questionnaire was sent to all the JSDT registered facilities (n=3484), and 480 centers replied (13.8%). Among these, 407 centers had patients introduced onto some form of RRT modality in the last 12 months. As to the adequacy of delivered IC for each modality, "excellent and good" status was reported as follows: 80.8% in HD, 49.8% in PD, and 32.5% in RTx, respectively. The major reason for "poor and bad" IC adequacy in PD and RTx, was "not available in the facility". By analyzing the facilities stratified by the clinical experiences of each modality in the past, poorly delivered IC for PD and RTx was revealed in centers lacking experience. Delivered information about RRT to ESRD patients may be biased in Japan. The findings of this study suggested that a lack of medical experience of the modality contributes to insufficient IC.
Disclosure↗
Correction of CAPD catheter displacement using alpha-replacement method.
BACKGROUND: Malposition of the tip of a continuous ambulatory peritoneal dialysis (CAPD) catheter may impede a dialysis, and an invasive method, such as open or laparoscopic surgery, is necessary to correct its position. The alpha-replacement method is a nonsurgical procedure; however, the reported clinical experience has been limited. We thus reviewed our 19 cases to clarify the efficacy of this method. METHOD: The alpha-replacement method was used in 19 patients [mean age, 50 +/- 14 years old; male/female ratio, 13/6; duration of catheter insertion, 23.7 +/- 23.9 months; total, 29 times in 19 patients (once in 13 patients, twice in 3, three times in 2, four times in 1 patient)]. All patients received a swan-neck J-type catheter. The procedure was carried out by using a special guidewire within 1-2 weeks after dislocation of the tips. RESULTS: The procedure was successfully performed 22 times in 14 patients (success rate, 78% in each performance). Required time was only 5-10 min in most successful cases. No evident complications were encountered in any case. CONCLUSIONS: The alpha-replacement method for a displaced CAPD catheter proved to be effective and safe.
Adult↗
Risk factors for encapsulating peritoneal sclerosis in patients who have experienced peritoneal dialysis treatment.
BACKGROUND: The present study was conducted to clarify the clinical risk factors related to the development of encapsulating peritoneal sclerosis (EPS), which is one of the most serious complications in patients undergoing peritoneal dialysis (PD). METHODS: The records of 78 patients with a history of PD treatment, including 18 with EPS, were retrospectively analyzed (male/female, 51:27; age, 51.8 +/- 11.0 years; PD treatment, 94.1 +/- 42.7 months). The inclusion criteria were: duration of PD more than 24 months; 36-month follow up after discontinuation of PD; available data for dialysate-to-plasma creatinine ratio (D/P Cr), by fast peritoneal equilibration test within 3 months before PD discontinuation; and absence of EPS at PD discontinuation. Analytical parameters included age, sex, underlying renal disease, duration of PD, membrane transport state (higher transporter or lower transporter: D/P cr ratio more than or less than 0.75), number of episodes of peritonitis during PD treatment, performance of peritoneal lavage after PD discontinuation, and reasons for PD withdrawal (ultrafiltration failure, acute peritonitis, social matters). RESULTS: Significant differences were noted regarding the PD duration, D/P cr, higher membrane transport state, and number of peritonitis episodes during PD. On receiver operating characteristic curves, the cutoff points for EPS were: D/P cr ratio, 0.74; number of peritonitis episodes, 2; and PD duration (months), 115.2. Multivariate analysis, employing the factors age, PD duration, higher membrane transport state, and number of peritonitis episodes, which were selected by stepwise analysis, identified the latter two factors as significant for the development of EPS (odds ratio [OR], 4.0; P = 0.046 and OR, 12.0; P = 0.049, respectively). CONCLUSIONS: A higher transporter membrane state and the number of peritonitis episodes are factors contributing to the occurrence of EPS in patients who have experienced PD treatment.
Adult↗
High iron storage levels are associated with increased DNA oxidative injury in patients on regular hemodialysis.
BACKGROUND: Accumulating evidence suggests that oxidative stress is enhanced in patients on regular hemodialysis (HD). Iron supplementation is essential for the treatment of renal anemia, but there is a possibility that it could enhance oxidative stress by inducing the Fenton reaction. Here, we report our investigation of the relation between iron storage and DNA oxidative injury in HD patients. METHODS: The study subjects were 48 patients on regular HD (age, 62.7 +/- 12.1 years; HD duration, 67.2 +/- 62.5 months; non-diabetic/diabetic; 22:26). Patients who were positive for hepatitis C virus antibody (HCV Ab), or hepatitis B surface antigen (HBsAg), and those with inflammatory or malignant diseases were excluded. The serum 8-hydroxy-2'-deoxyguanosine (8-OHdG) level, a marker of DNA oxidative injury, was measured before the first HD session of the week in all patients, and factors associated with high serum 8-OHdG were investigated. In 9 patients with a serum ferritin level of more than 1000 ng/ml at study entry, serum 8-OHdG levels were followed up for 6 months in the absence of iron supplementation. RESULTS: Multivariate analysis showed that the serum ferritin level was a significant and independent determinant of serum 8-OHdG, and serum ferritin correlated significantly with the total dose of iron supplementation during the 6-month period of the study. In the nine patients, without iron supplementation, serum 8-OHdG levels, as well as serum ferritin, decreased significantly during follow-up. CONCLUSIONS: Our results suggest that increased iron storage may induce DNA oxidative injury in patients on regular HD, and that the serum ferritin level is a surrogate marker for this pathological condition.
8-Hydroxy-2'-Deoxyguanosine↗
Significance of screening for Fabry disease among male dialysis patients.
BACKGROUND: Fabry disease is an X-linked disorder resulting from a deficiency of the lysosomal enzyme alpha-galactosidase A(alpha-Gal A). Renal insufficiency is a very important manifestation and affects the prognosis of patients. Recently, a renal variant type that is characterized by low plasma alpha-Gal A activity and a milder phenotype, but which progresses to end-stage renal failure, has been reported. In this study, we clarified the incidence of this atypical variant of Fabry disease in hemodialysis patients. METHODS: We measured plasma alpha-Gal A activity in 450 male dialysis patients who had never been diagnosed with Fabry disease. RESULTS: The mean of the alpha-Gal A activity of the patients was 9.75 +/- 3.20 nmol/h/ml, while the controls with classical Fabry (n = 3) were 0.52-1.04 nmol/h/ml. Among the patients, one patient was found to exhibit low alpha-Gal A activity in plasma (3.18 nmol/h/ml) and in leukocytes (0.639 nmol/h/mg). This patient was a 43-year-old Japanese man who had been on regular dialysis since the age of 23. He did not present typical clinical signs of classical Fabry, such as acroparesthesias or hypohidrosis, but did present renal insufficiency and severe left ventricular hypertrophy which had developed only recently, suggesting a variant form of Fabry disease. Sequencing of the DNA of this patient revealed a deletion of a single amino acid of valine in 10252. CONCLUSIONS: A case of an atypical variant of Fabry among 450 male dialysis patients (0.22%) was found in the survey. This indicates the potential for undiagnosed Fabry disease among dialysis patients. The results of this study indicate the significance of screening for Fabry disease among male dialysis patients.
Adult↗
Restoration of peritoneal integrity after withdrawal of peritoneal dialysis: characteristic features of the patients at risk of encapsulating peritoneal sclerosis.
BACKGROUND: The epidemiological characteristics of encapsulating peritoneal sclerosis (EPS), such as its high incidence in patients with long-term peritoneal dialysis (PD) treatment, and the onset of EPS after patients are switched to hemodialysis (HD) may indicate an activated pathological process after PD withdrawal, especially in long-term PD patients. Accordingly, we aimed to observe changes in peritoneal function after the stoppage of PD, and to clarify the characteristic features of the patients at risk of EPS. METHODS: Thirty-three patients who were switched from continuous ambulatory peritoneal dialysis (CAPD) to HD were enrolled in this trial. Changes in the dialysate/plasma creatinine (D/P Cr) and CA125 levels in the effluent of the peritoneal equilibration test were observed for 6 months. Furthermore, each patient was followed-up for 36 months after PD withdrawal to monitor for the development of EPS. RESULTS: D/P Cr decreased significantly, while CA125 levels tended to increase. Nine patients developed EPS during the follow-up period and they specifically showed significant increases of D/P Cr levels and significantly lower levels of CA125 at PD withdrawal. The accumulation of high transporters in the EPS group at 0 and 6 months after PD withdrawal was significant. CONCLUSIONS: Peritoneal recovery may take place after withdrawal from PD treatment and such recover indicated by improvement of transport states and a rise of the CA125 level. The present study revealed that a high-transport state and lack of increase of CA125 in the effluent were associated with EPS development after PD withdrawal. This may suggest that the lack of peritoneal recovery after PD withdrawal is predictive for EPS development.
CA-125 Antigen↗
Photoluminescence properties of CdS and CdMnS quantum dots prepared by a reverse-micelle method.
We have investigated photoluminescence properties of CdS and CdMnS quantum dots (QDs) prepared by a reverse-micelle method. Before the surface modification, a broad luminescence band that originates from defects is dominant in CdS QDs. By the modification, the intensity of the band-edge luminescence is remarkably increased. The surface modification also causes drastic changes of decay profiles of the band-edge luminescence. The intensity of Mn2+ luminescence originating from the intra-3d shell transition of Mn2+ is also increased by the surface modification of CdMnS QDs. The decay time of the band-edge luminescence in surface-modified CdMnS QDs is faster than that in CdS QDs, which is due to the energy transfer from excitons to Mn2+.
Journal Article↗
Cytotoxicity and recognition of receptor-like protein tyrosine phosphatases, RPTPalpha and RPTPbeta, by Helicobacter pylori m2VacA.
Helicobacter pylori vacuolating cytotoxin, VacA, induces vacuolation in mammalian cell lines. Sequence differences in the middle of VacA molecules define two families, termed m1VacA and m2VacA, which differ in cell specificity. Similar to m1VacA, m2VacA is activated by acid or alkali, which enhances its binding to cells. Immunoprecipitation experiments showed that, in AZ-521 cells, activated m2VacA, similar to m1VacA, binds to two receptor-like protein tyrosine phosphatases, RPTPalpha and RPTPbeta suggesting that activated m2VacA as well as m1VacA may contribute to gastrointestinal disease following H. pylori infection. G401 cells express RPTPalpha, not RPTPbeta, and responded to both m1VacA and m2VacA. HeLa cells likewise expressed RPTPalpha, not RPTPbeta, but, in contrast to other cell lines, responded poorly to m2VacA. m1VacA associated with RPTPalpha of HeLa cells to an extent similar to that in other toxin-sensitive cells, whereas activated m2VacA bound HeLa cell RPTPalpha less well, consistent with its low vacuolating activity against these cells. The molecular mass of RPTPalpha from HeLa cells is less than that of the protein from G401 cells, although their extracellular amino acid sequences are virtually identical, with only two amino acid differences noted. Different post-translational modifications of RPTPalpha in HeLa cells may be responsible for the reduced susceptibility to m2VacA.
Adenocarcinoma↗
[Peritoneal injury and vasculopathy in peritoneal dialysis].
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Glycation End Products, Advanced↗
Encapsulating peritoneal sclerosis is a separate entity: Con.
There is controversy with respect to the issue that encapsulating peritoneal sclerosis (EPS) is a separate entity from simple sclerosis (SS), which is the uniform change of the peritoneum on peritoneal dialysis. These following ideas support the notion that the development of EPS is connected with pathology that is not the same as that responsible for SS: (1) EPS is a rare disorder, (2) certain factors are involved with the etiology, (3) the clinical background of the patients is not uniform, and (4) the histopathological findings of EPS are different from those of SS. There are pitfalls in these concepts and they need be revised. This paper discusses the issue against the idea that EPS is a separate entity, supporting the idea that it has a strong connection with SS in its primary pathophysiology.
Humans↗
[Dialysis as bridge therapy for renal transplantation: single center experience, a comparison of hemodialysis and continuous ambulatory peritoneal dialysis].
BACKGROUND: Kidney transplantation is the most ideal treatment in renal replacement therapy for patients with end-stage renal disease. However, the prevalence of transplantation is extremely low and most patients with ESRD should continue dialysis for their whole life. Recently, high transposition rate of renal transplantation from peritoneal dialysis (PD) was reported, however, it was unclear whether a difference in dialytic modality can influence the outcome. Therefore, we evaluated the influence of dialytic modality on the rate of kidney transplantation and outcome in our single center. METHODS: Forty-two kidney transplants were carried among 1,573 dialysis patients from the years 1986 to 2004 in our center. Transposition rates from two modalities (HD and PD) and graft survival were compared. The incidence of acute rejection episode, complications after receiving transplantations, and coexisting diseases were also evaluated between the two modalities prior to transplantation. RESULT: The number of patients who received HD was larger than PD (HD 77.1%, PD 22.9%, respectively). Forty-two patients undergoing dialytic therapy received a living-donor kidney transplantation. Overall graft survival was 92% at 5 years and 75% at 10 years. Among these cases, dialytic modality prior to transplantation was 57.1% in HD, and 42.9% in PD. The transfer rate from PD to transplantation was significantly (p = 0.0036) higher (4.7%) than that of HD (1.9%). The reason for the high transfer rate of PD patients might be cooperation with their family and the provision of relevant information by nephrologists during PD. There were no differences between the two modalities prior to transplantation in the graft survival rate, incidence of acute rejection, and complications before and after transplantation. CONCLUSION: Difference in pretransplant dialysis modality did not affect the outcomes, however, the transfer rate from PD was significantly higher than from HD. Accordingly, PD is useful compared to HD as bridge therapy for kidney transplantation from the high feasibility of living-donor kidney transplantation.
Adult↗
The plasma leak-to-response hypothesis: a working hypothesis on the pathogenesis of encapsulating peritoneal sclerosis after long-term peritoneal dialysis treatment.
Encapsulating peritoneal sclerosis (EPS) is one of the most serious complications of long-term peritoneal dialysis (PD). Long-term PD therapy has been suggested as a risk factor for EPS development among patients in Japan and Australia. Although the primary mechanism of EPS development has not been clarified, histologic changes of the peritoneum associated with prolonged PD are postulated to be causally related. The present article proposes a working hypothesis--the plasma leak-to-response hypothesis--that vascular alterations in the peritoneum of long-term PD patients play a crucial role in the initiation and development of EPS.
Humans↗
Recommendations on the management of encapsulating peritoneal sclerosis in Japan, 2005: diagnosis, predictive markers, treatment, and preventive measures.
This comprehensive update on the management of encapsulating peritoneal sclerosis incorporates insights gained from recently published findings and the accumulated experience of the authors. Aspects covered include diagnosis, risk factors and predictive markers, treatment, and prevention, including criteria for withdrawal from peritoneal dialysis.
Biomarkers↗
[Structure and intoxication of VacA].
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Animals↗