Sadanori Shintaku

Efficacy of HSP72 induction in rat liver by orally administered geranylgeranylacetone.

Abstract It is well known that heat‐shock proteins (HSPs) have a cyto‐protective function as “molecular chaperones” when cells are exposed to several stress conditions. Geranylgeranylacetone (GGA) is an antiulcer drug that was developed in Japan and it has recently been reported to induce HSP72 in rat gastric mucosa. In this experiment, we investigated the induction of HSP72 in rat liver in response to oral administration of GGA and assessed its ability to induce tolerance to warm ischemic injury by this approach. We prepared donor rats by orally administering GGA to them and compared HSP72 expression in graft liver, survival rates, and serum TNF‐α concentrations after liver transplantation with the findings in controls. The survival rates were significantly increased when the livers were obtained from donor rats given GGA. Western blotting revealed expression of HSP72 in graft livers given GGA, and the serum TNF‐α levels were significantly suppressed in the rats given GGA. Oral administration of GGA induced HSP72 in graft livers, and they were better able to tolerate warm ischemic injury. Oral administration of GGA appears to provide a promising new strategy for preventing ischemia‐reperfusion injury.

Monitoring for engraftment following rat orthotopic liver transplantation by in vitro amplification of Y-chromosome gene using polymerase chain reaction

The polymerase chain reaction (PCR) using primers specific for the rat Y-chromosome gene made it possible to distinguish a very small number of male rat cells from a large excess of female rat cells. In nonimmunosuppressed LEW recipients of ACI liver allografts, the donor cells in the bloodstream disappeared rapidly by day 3, earlier than the biochemical changes indicative of liver dysfunction. In immunosuppressed LEW recipients of ACI liver allografts, the donor cells were detected for a longer time. Moreover, in LEW recipients surviving for long period, the PCR revealed mixed-microchimerism. Our results indicated that this Y chromosomal gene-specific PCR method is useful for assessing engraftment following rat liver transplantation.

Modified MILLER banding procedure for managing high-flow access and dialysis-associated steal syndrome

Purpose Both high-flow vascular access (VA) and dialysis-associated steal syndrome are serious complications requiring a flow reduction technique. We adopted the minimally invasive limited ligation endoluminal-assisted revision (MILLER) banding procedure with some modifications to control the high blood flow and steal syndrome during VA procedures and retrospectively assessed the outcome. Methods Seven patients with high-flow access (access flow >1400 ml/min) and five patients with steal syndrome (with pain, coldness, or cyanosis) were treated using the MILLER banding method. Flow volume of the brachial artery was monitored using Doppler ultrasonography during the banding procedure. In patients with steal syndrome, the finger probe of a pulse oximeter was attached to a finger on the ipsilateral side, and the peripheral oxygen saturation (SpO2) was monitored. Results In the high-flow group, the mean access blood flow (Qa) decreased from 2043 ± 463 ml/min (mean ± SD) to 1248 ± 388 ml/min (p<0.001). In the steal syndrome group, the SpO2 value improved in all steal syndrome patients after banding. Symptoms were almost relieved in two steal syndrome patients. The Qa in the steal group decreased from 997 ± 867 to 548 ± 376 ml/min (p = 0.12). The secondary patency rates of the high-flow and steal groups at 6 months were 83.3% and 50%, respectively. Conclusions The MILLER banding procedure with intraoperative access flow monitoring is effective to treat high-flow VA and steal syndrome.

Effect of FTY720 on immunoregulation in concordant xenotransplantation.

Abstract The present study was designed to analyze the immunosuppressive activity of FTY720 in concordant xenotransplantation. When T and B lymphocytes of human peripheral blood were incubated with FTY720, the number of viable cells decreased in a dose‐dependent manner at doses higher than 4×10‐5 M. DNA fragmentation was observed at doses higher than 4×10 ‐5 M in B cell‐rich fractions. These data demonstrate that FTY720 is cytotoxic to B lymphocytes as well as T lymphocytes and apoptosis may play an important role in this cytotoxicity. Golden Syrian hamsters were the donors and Lewis rats the recipients of skin grafts. The recipients were divided into the following four groups; (1) untreated recipients, (2) FTY720 (5mg/kg per day) was administered orally for 8 days (days ‐1–6), (3) FK 506 (1 mg/kg per day) was injected i. m. for 7 days (days 0–6), and (4) FK506 (1 mg/kg per day) was injected i.m. for 7 days (days 0–6) and FTY720 (5 mg/kg per day) was administered orally for 8 days (days‐1–6). The mean graft survival times in groups 1–4 were.7 ± 0.52 days (n= 6), 12.0 ± 0.71 days (n= 6), 13.2 ± 1.6 days (n= 6), and 37.7 ± 4.3 days (n= 6), respectively. There was a significant difference in the mean survival time between groups one and four. Combined therapy with FTY720 and FK506 is a useful tool for immunoregulation in xenotransplantation.

Hypomagnesemia as a predictor of mortality in hemodialysis patients and the role of proton pump inhibitors: A cross-sectional, 1-year, retrospective cohort study.

Introduction This study aimed to evaluate the association between proton pump inhibitor (PPI) use and serum magnesium levels, and the role of hypomagnesemia and PPI use as a risk factor for mortality in hemodialysis patients.

Distal ulnar-basilic fistula as the first hemodialysis access

Purpose A distal forearm ulnar-basilic (UB) arteriovenous fistula (AVF) can be chosen if a radial-cephalic (RC)-AVF is not suitable for a primary AVF. However, limited data are available on the feasibility of using a distal forearm UB-AVF as an option for primary AVF. Methods This retrospective analysis included 446 patients for whom AVFs (417 RC and 29 UB) had been newly created from January 2003 to December 2009, at our hospital. Patients in whom the arterial or venous anatomy precluded RC-AVF creation, UB-AVF was established as distally as possible on the forearm. Patency, defined as access survival after creation, was calculated using Kaplan-Meier analysis. The difference in patency between the two groups was examined using log-rank test. Results The primary patency of UB-AVFs was significantly lower than that of RC-AVFs (p=0.037, log-rank test). The primary patency rate at 1 year was 25.0% versus 44.7%, respectively. However, there was no significant difference in secondary patency between the two groups. The secondary patency rate at 1 year was 85.5% for UB-AVFs versus 82.9% for RC-AVFs. The incidence rate of percutaneous angioplasty until access abandonment per patient-years was 1.100 for UB-AVFs versus 0.671 for RC-AVFs. There was no difference in the time to maturation between the two groups. Conclusions The secondary patency rate of UB-AVF is similar to that of RC-AVF. We recommend the creation of an UB-AVF when an RC-AVF is not a suitable option for the primary AVF.

Vascular access in super-aged patients

Purpose In developed countries, dialysis patients are aging along with the general population. The choice of vascular access (VA) is a more complex decision among elderly patients and is not specifically addressed by clinical practice guidelines. We investigated the relationship between the VA type at dialysis initiation in elderly patients and their prognosis, as well as the selection of the optimal VA type. Methods We conducted a retrospective observational cohort study of consecutive adult patients (age ≥18 years) as their first form of renal replacement therapy (RRT) between January 1, 2003, and December 31, 2010. For this study, VA included both arteriovenous fistula (AVF) and temporary central venous catheter (CVC). Results A total of 402 patients were included in this study. The percentage of patients who started dialysis with CVC increased with age, and 63% of those were over 80 years. The survival rate in the group of elderly patients (≥70 years) using CVC at dialysis initiation was significantly lower. In contrast, the survival rates were comparable between nonelderly patients (<70 years) using CVC or AVF. One hundred and thirty patients were super-aged (≥80 years). In super-aged patients (≥80 years) and aged patients (70-79 years), dialysis initiation with CVC was correlated with a significantly poorer survival rate than dialysis initiation with AVF. The survival rates were comparable between the low CRP group (<1.8 mg/dL) using CVC or AVF. Conclusions The initiation of dialysis with temporary CVC is not a risk factor of death in nonelderly patients (<70 years). On the other hand, in elderly (≥70 years) and super-aged (≥80 years) patients, dialysis initiation with CVC increased the risk of death, but they had to start dialysis with CVC on an emergency basis because of their clinical condition, that is, inflammations.

Expression of bcl-2 homologue mRNAs in rat liver allograft: rejection-induced cell apoptosis is associated with upregulation of bax and bcl-xs expression

Abstract Apoptosis is considered to play an important role in rejection of organ transplants, although the precise mechanism has not been elucidated. In this study, we screened for the expression of bcl‐2 homologues (bcl‐2, bax, bcl‐xl, and bcl‐xs) and Fas ligand (FasL) by RT‐PCR method in grafts during acute rejection in rats following liver transplantation. Both bax and bcl‐xs (inducers of apoptosis) mRNA levels increased steadily in the allografted group from postoperative day (POD) 2 to 8, while no remarkable changes of bcl‐2 and bcl‐xl expression (inhibitors of apoptosis) were recognized. Significant induction of FasL gene expression was observed in the allografted group on POD 4 and expression gradually decreased thereafter, although minimal FasL mRNA expression was seen in isografts. Our results indicated, for the first time, that rejection‐induced cell apoptosis is closely associated with upregulation of bax and bcl‐xs expression besides FasL, but not with down‐regulation of bcl‐xl.

Expressions of p53 and PCNA do not correlate with the international index or early response to chemotherapy in non‐Hodgkin's Lymphoma

The expression of p53 and PCNA on deparaffinized sections of tumor was assessed in relation to the International Index and response to chemotherapy. Thirty‐five non‐Hodgkins lymphoma (NHL) patients were divided into three groups: aggressive NHL, mantle cell lymphoma (MCL), and low‐grade NHL. None of the expressions correlated with the International Index or early response to chemotherapy in any group. In low‐grade NHL, none of the patients expressed p53. Only one of three patients with overexpression of p53 showed conformational change and alteration of sequence in exon 7 by PCR‐SSCP and DNA sequencing. The results showed that p53 and PCNA staining were not useful for predicting early response to chemotherapy, and that their expressions had no correlation with the International Index. Am. J. Hematol. 58:42–48, 1998.

Past and Present Perspectives on Encapsulating Peritoneal Sclerosis

Encapsulating peritoneal sclerosis (EPS) is a serious complication of long-term peritoneal dialysis. The mortality rate for EPS has been high, primarily due to complications related to bowel obstruction. However, recent advances in clinical research have established the pathogenesis, the disease course, and a treatment strategy. Currently, there is consensus on therapy; however, treatment with corticosteroids and tamoxifen should be administered in a timely manner. The final therapeutic option for EPS is surgical enterolysis (adhesiolysis). Moreover, a biocompatible peritoneal dialysis solution has become available for patients worldwide, which may further reduce peritoneal deterioration and EPS risk. These activities have promoted a better understanding of and have prompted countermeasures against EPS. EPS is no longer considered a fatal complication.