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R Sumimoto

Publications and source records attributed to R Sumimoto.

At least 19 recordsLinked to original sources
PubMed2001

[Effectiveness of high-dose, intermittent 5'-DFUR therapy for advanced gastric cancer].

We report a case of advanced gastric cancer with multiple liver metastases and peritoneal dissemination. The patient was effectively treated with high-dose 5'-DFUR. A 52-year-old patient with advanced gastric cancer and multiple liver metastases, who showed a high serum level of CEA and CA19-9 underwent simple D1 gastrectomy. Thereafter, he received per os 1,200 mg/day of 5'-DFUR intermittently (5 days a week) and TAI every four months postoperatively. The serum levels of both CEA and CA19-9 fell dramatically to within the normal range and were maintained thereafter until the present. The size and number of the liver metastases dramatically decreased, judging from CT and angiography findings.

Adenocarcinoma↗
PubMed1998

Establishment of chimerism in donor liver with recipient-type bone marrow cells prior to liver transplantation produces marked suppression of allograft rejection in rats.

In this study, we investigated whether establishment of chimerism in donor liver with recipient-type bone marrow cells (BMCs) prior to liver transplantation could prolong the liver allograft survival. Donor female ACI rats were inoculated with recipient-type BMCs of male LEW rats via the portal vein, with or without irradiation as cytoablation, followed by intramuscular administration of FK506 for 5 days. At 1-2 months later, livers were harvested and transplanted into naive female LEW rats. No immunosuppressants were used. Chimerism in donor rats was confirmed by primers specific for the sex determinant Y chromosome of rats. With livers from rats pretreated with recipient-type BMCs, survival of liver allografts was significantly extended, irrespective of irradiation. These results showed that modification of the donor liver by intraportal injection of recipient-type BMCs and concomitant administration of FK506 prior to liver transplantation prolonged liver allograft survival in rats.

Animals↗
PubMed1998

TNF-alpha and heat-shock protein gene expression in ischemic-injured liver from fasted and non-fasted rats. Role of donor fasting in the prevention of reperfusion injury following liver transplantation.

We have previously shown that livers from long-term-fasted rats acquire tolerance to warm ischemic injury following transplantation, despite the fact that fasting depletes glycogen and ATP from the liver. The precise mechanism of the protective effect induced by donor fasting, however, is still a matter of controversy. In this experiment we determined heat-shock protein (GRP78) mRNA expression in livers during long-term fasting and TNF-alpha mRNA expression in transplanted livers exposed to warm ischemia. We also measured the concentration of TNF-alpha by ELISA in the ascitic fluid of fed and fasted rats injected intraperitoneally with zymosan to investigate why livers from fasted rats tolerate ischemic injury better. There seemed to be a positive correlation between GRP78 mRNA expression and survival. TNF-alpha secretion into the ascitic fluid of fasted rats was markedly suppressed, and fasting donor animals induced cytoprotective substances, such as GRP78, in the liver. These factors may contribute to the tolerance to ischemic injury produced by donor fasting.

Animals↗
PubMed1998

The outcome of liver transplantation at various times (70, 120, and 134 days) after the initiation of carcinogenesis in rats.

The therapeutic results of liver transplantation for primary liver cancer have not been satisfactory. The high rate of recurrence appears to be due to the inadequate care taken in selecting the most appropriate candidates for orthotopic liver transplantation (OLT), the presence of circulating hepatocellular carcinoma (HCC) cells and micrometastases at the time of liver transplantation, and the tumor growth-promoting effects of immunosuppressive agents. We believe that HCC patients must be carefully staged in order to identify those most suitable for OLT. We therefore induced HCC in pure-strain rats by the oral administration of diethylnitrosamine (DEN) and studied the outcomes of liver transplantation at various time points (70, 120, and 134 days) after the initiation of carcinogenesis. The mean survival time (MST +/- SD) of the non-OLT control group (N = 14) was 18.2 +/- 5 days after Day 120. The survival time of the four rats in the OLT Day 120 group was 81.3 +/- 20.6 days after transplantation. One rat showing full weight recovery soon after transplantation survived for 97 days after transplantation and then succumbed to recurrence. The survival time of the four rats in the OLT Day 134 group was 7.3 +/- 5.0 days after transplantation. The survival time of the three rats in the OLT Day 70 group was 145.3 +/- 70.0 days after transplantation, with a maximum survival of 221 days until death. Significantly prolonged survival, as compared with that in the non-OLT group, was observed in the OLT Day 70 and OLT Day 120 groups (p < 0.01), while there was no significant prolongation in the OLT Day 134 group (NS). The timing of liver transplantation is a very important factor. Preoperative assessment of factors potentially affecting recurrence in HCC patients is imperative for selecting the most appropriate candidates for OLT. Careful selection of candidates for OLT should always be considered the key to successful liver transplantation (i.e., long-term survival) for patients with liver cancer.

Animals↗
PubMed1998

Examination of serum class I antigen in allograft recipient rats--origin and control of serum class I antigen.

We examined the appearance of DA type (RT1Aa) class I antigen in the serum of rats that had received isogeneic or allogeneic liver grafts (DA into DA, DA into LEW, PVG into DA, PVG into F1 hybrid (DAxPVG). Recipient LEW rats were given either one injection of the anti-CD8 mAb, OX-8, following thymectomy or anti-CD4 mAb (cocktail of OX-35 and OX-38) following thymectomy 3 days prior to liver grafting. We also tested the serum RT1Aa antigen titer of F1 (DAxPVG) recipients after PVG spleen transplantation and the serum RT1Aa antigen titer in the DA rat after hepatectomy and cyclosporin treatment. Replacement of DA liver by PVG lowered transiently the serum level of RT1Aa antigen to 70% of that in normal DA serum shortly after liver transplantation. However, this titer increased gradually over the level in normal DA serum. A PVG spleen graft to an F1 hybrid recipient resulted in death due to typical GVH disease between 13 and 24 days after spleen transplantation. The RT1Aa antigen titer increased to several times more than that in normal F1 serum throughout the observation period. LEW recipients of DA liver died at 9-11 days (9.8 +/- 1.1 days) due to acute liver rejection. In this combination, the serum level of RT1Aa increased until day 8, reaching a maximum (four times) on day 4. Deletion of either CD8+ or CD4+ T cells by anti-CD8 or anti-CD4 MAb in this transplantation prolonged the survival times of liver grafts for up to 26.8 +/- 8.4 and 35.6 +/- 17.9 days, respectively. In the anti-CD8 or anti-CD4 MAb- treated recipients, the serum titer of DA class I antigen was not elevated and there were no differences between the two. Hepatectomy in combination with cyclosporin induced a higher titer of liver-derived class I antigen in the serum as long as liver regeneration proceeded. These results suggest that the liver is the principal source of serum class I antigen in rats. Rejection, GVH reaction and liver regeneration increased the serum class I antigen from transplanted liver or host tissue. It is unlikely that this is due to cleavage of membranous class I antigen by class I- reactive CD8+ T cells.

Animals↗
PubMed1998

Examination of serum amyloid A protein in kidney transplant patients--comparison of serum amyloid A and C-reactive protein for monitoring the occurrence of renal-allograft-related complications.

Serum amyloid A (SAA) is an inflammation-reactive protein, like C-reactive protein (CRP). In this study, we examined SAA levels in the sera of kidney transplant patients with acute rejection (N = 12), chronic rejection (N = 60) and cytomegalovirus (CMV) infection complications and compared them with serum CRP levels in terms of sensitivity and reactivity. The SAA and CRP showed almost similar kinetics in 10 patients within 2 months of kidney transplantation. However, in 2 patients SAA responded more sensitively to CMV infection and acute rejection. SAA increased significantly 10-fold relative to its baseline levels. The SAA levels also increased along with those of serum creatinine levels. Our experiments clearly showed that SAA and CRP responded sensitively to several stimuli with elevated serum levels including surgical trauma, acute allograft rejection and infection. However, the reactivity and sensitivity of SAA was clearly higher than those of CRP in patients with viral infections, on steroid therapy and undergoing chronic allograft rejection, suggesting that monitoring SAA levels provides more useful information than monitoring CRP.

Biomarkers↗
PubMed1997

Inhibition of warm ischemic injury to rat liver, pancreas, and heart grafts by controlling the nutritional status of both donor and recipient.

In this study, we tested the effect of donor fasting with or without the use of an essential fatty acids deficiency (EFAD) diet in the recipient using rat heart, pancreas, and liver transplant models. We then compared the survivals, tumor necrosis factor alpha (TNF-alpha) response, and white cell accumulation in rats in order to clarify the mechanisms of the beneficial effect of donor fasting and recipient EFAD. It was found that when the grafts were obtained from fasted donors and then transplanted into fed recipients, the survival rate was significantly higher for all three grafts than for those obtained from fed rats and transplanted into fed rats. The best survival was seen for pancreas grafts obtained from fasted donors and then transplanted into EFAD recipients. TNF-alpha secretion was significantly suppressed in both fasted and EFAD rats, and both the total cell count and neutrophil count were suppressed in EFAD rats. These results clearly indicate that in addition to liver grafts, both heart and pancreas grafts obtained from fasted animals are more tolerant to warm ischemic injury. Furthermore, the combination of donor fasting and recipient EFAD acts synergistically to inhibit the post-transplantation inflammatory reaction (through decreased TNF-alpha secretion and white cell accumulation), thus resulting in an improved survival.

Animals↗
PubMed1996

Synergistic effects of nafamostat mesilate rinse and Kupffer cell blockade for rat liver preservation.

We investigated the efficacy of a new rinse solution containing nafamostat mesilate (NM) (a serine protease inhibitor) for liver preservation with modulation of Kupffer cell function. Orthotopic liver transplantation (OLT) was performed in male Lewis rats after 24 h of cold storage in University of Wisconsin organ preservation solution. After OLT, survival was determined, together with assays of blood chemistry, tissue NM metabolites, and histology 3 h after OLT. NM rinse was found to have a cytoprotective effect on liver parenchymal cells, based on enzyme data showing that NM rinse reduced the release of serum alanine aminotransferase significantly in comparison with saline rinse (P < 0.05). However, the effect was not sufficient to improve the survival rate. In contrast, when the donor was treated with gadolinium chloride 24-30 h before graft harvest, NM rinse improved the survival rate to around 80% compared with 25% for saline. The assay of NM metabolites in grafted liver tissue showed that pretreatment of the donor rats with GdCl3 delayed the degeneration of NM in the liver tissue. These data demonstrate that NM rinse and Kupffer cell blockade exert synergistic effects, leading to increased survival after cold-preserved liver transplantation.

Animals↗
PubMed1996

Liver glycogen in fasted rat livers does not improve outcome of liver transplantation.

Controversy exists over how the nutritional condition of the donor liver affects transplant outcome. Some studies suggest that livers from fasted animals (liver glycogen-depleted) are more readily injured than livers from fed animals. Our previous study suggested the opposite, i.e., livers from donors fasted for 4 days were significantly more viable on orthotopic liver transplantation. Fasting may decrease the sensitivity of the liver to an inflammatory response or block Kupffer cell activation following transplantation. Thus, long-term fasting may be beneficial for reasons unrelated to liver glycogen content. In this study we attempted to separate out the roles of fasting and liver glycogen in liver transplant outcome by fasting donors for 2 days and then feeding them only glucose to elevate liver glycogen. Rats (Brown Norway) were fed (standard diet), fasted (4 days), or fasted 2 days and then fed glucose (in water) for 2 days. Livers were preserved for either 30 or 44 h in UW solution and transplanted. Four-day fasting of the donor improved the survival rate in liver transplantation (50%-100% in 30-h cold storage, 29%-83% in 44-h cold storage). However, feeding glucose for 2 days to fasted animals caused a decrease in survival in this series of transplants (40% in 30-h cold storage, 0% in 44-h cold storage). In the glucose-fed group, liver glycogen was 240% of that in the control group. This suggests that the presence of a high concentration of liver glycogen is not beneficial to the preserved and transplanted rat liver.

Animals↗