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S Tashiro

Publications and source records attributed to S Tashiro.

At least 19 recordsLinked to original sources

Significance of administration of fat emulsion: hepatic changes in infant rats receiving total parenteral nutrition with and without fat.

Total parenteral nutrition (TPN) is associated with cholestasis and hepatic steatosis, which can be lethal in infants who cannot be fed orally. The present animal study focused on the metabolic complications in the liver that may occur due to the excessive administration of fat-free TPN. Thirty infant (3-week-old) male SD rats weighing 60-70 g were randomly allocated to five groups (n = 6): the OD group received an oral diet, the FT group received an oral diet and was fasted overnight on the last day of experiment before sacrifice, the 0% fat group received TPN without fat, the 20% fat group received TPN with 20% of calories from fat emulsion, and the 40% fat group received TPN with 40% of calories from fat emulsion. All TPN regimens were isocaloric, isonitrogenic, and administered for 4 days. In the 0% fat group, plasma levels of liver enzymes were significantly higher than in the other groups. Pathological examination showed hepatomegaly and severe fatty changes without cholestasis in the 0% fat group. The results of this study in infant rats indicate the importance of including fat in the TPN regimen in order to prevent the abnormal hepatic changes associated with the excessive administration of fat-free TPN.

Alanine Transaminase↗

A new system for laser-UVA-microirradiation of living cells.

Local nuclear irradiation of living cells has been used to gain insight into the dynamic changes that cell nuclei undergo in response to DNA damage. In particular, the effects of DNA double-strand breaks (DSBs), a major threat to the genomic integrity of cells, have been studied by local nuclear irradiation with ionizing radiation. This method has the disadvantage that it requires expensive equipment to generate a sufficiently high density of focused or collimated ionizing radiation. After appropriate sensitization of the cellular DNA, nuclear microirradiation with UVA can also produce DSBs. In this communication we present a semi-automatic system for laser-UVA-microirradiation based on a commercial laser scanning microscope. The system allows the convenient selection and precise irradiation of living cells, and could provide the basis for a more widespread availability of microirradiation facilities for DNA-repair research.

Calibration↗

Neonatal ketosis is not rare: experience of neonatal screening using gas chromatography-mass spectrometry.

The causes and effects of transient neonatal ketosis, discovered during a pilot study of screening for abnormalities in neonatal metabolism using gas chromatography-mass spectrometry, were investigated. Of the 21,342 neonates that were screened, 47 had significant ketosis. The organic acid profile accompanying ketosis in the urine of neonates followed the pattern of ketotic dicarboxylic aciduria in approximately half of the cases. Ketosis was more often found in neonates nourished by breast feeding (33 out of 47). Over half of the neonates showing ketosis (28 out of 47) were asymptomatic. When normal neonates and neonates testing positive for ketosis were compared, no statistically significant correlations were found with regard to birth mass, gestational period, or gender. However, neonates with ketosis tended to have low mass gain rates in the 5 days from birth and a statistically significant difference was found in this regard in comparison to normal neonates (P<0.0001). From the above results, development of ketosis in neonates was found to be possible even in normal subjects. Most ketosis in neonates was also found to depend largely on nourishment after birth. Existence of an asymptomatic ketosis category was also suggested.

Gas Chromatography-Mass Spectrometry↗

Simultaneous resection of pancreas and liver metastases from different metachronous primary cancers.

Resection of a pancreatic head tumor and partial resection of the liver for metastatic lesions were carried out simultaneously in a 72-year-old woman. The patient had a history of two previous operations, right nephrectomy for renal cell carcinoma (clear cell type), done 14 years previously, and an Autincloss procedure for cancer of the left breast (solid tubular carcinoma); (T1N0M0; stage I) done 7 years previously. At the current presentation, preoperative radiographic examination showed a hypervascular tumor in each of the pancreatic and hepatic lesions, but with different patterns. On the basis of histological findings in the two resected specimens, it was difficult to establish whether the hepatic tumor originated from the renal cell carcinoma or the breast cancer, but postoperative immunohistochemical studies for carcinoembryonic antigen (CEA), estrogen receptors, and gross cystic disease fluid protein (GCDFP)-15 showed that the pancreatic tumor had metastasized from the renal cell carcinoma, and the liver tumor from the breast cancer. The immunohistochemical investigation of different markers thus proved to be useful in making the final diagnosis of metastatic lesions from different and metachronous cancers.

Aged↗

Evaluation of the acetaminophen absorption test for early detection of orthotopic small bowel transplant rejection.

We evaluated the efficiency of the acetaminophen (AC) absorption test as a marker of graft rejection in orthotopic small bowel transplantation (SBTX) in rats. Brown Norway (BN) rats were used as donors and Lewis (LEW) rats as recipients. Orthotopic allogenic SBTX was accomplished using a cuff technique for vessel anastomosis. Animals were divided into: group A (n = 9), untreated; group B (n = 15), extended small bowel resection; group C (n = 12), syngeneic SBTX without immunosuppressants; group D (n = 15), allogenic SBTX with tacrolimus (0.1 mg/kg per day); group E (n = 15), allogenic SBTX with tacrolimus (0.5mg/kg per day). Serum AC was measured 15 min following the instillation of 0.15 g/kg AC into the stomach on postoperative days (POD) 1, 3, and 7. Grafts were examined histologically. The group D grafts showed progressive acute rejection histologically, from normal on POD 1, to moderate on POD 3, and severe on POD 7. Serum AC in group D decreased significantly from 53.1 +/- 3.9 microg/ml on POD 1, to 35.0 +/- 12.0 microg/ml on POD 3, and 10.9 +/- 5.6 microg/ml on POD 7. No remarkable change was observed in the other groups. Serum AC correlated well with histological changes in rats subjected to SBTX, resulting in acute rejection. The AC absorption test could be useful for detection of progressive graft rejection in clinical SBTX.

Absorption↗

Effect of intrahepatic omental implantation on angiogenesis in rat liver with hepatic artery ligation.

Despite early surgical intervention, the results of treating hepatic artery thrombosis remain poor. The use of omental flaps is well documented for its angiogenic potential in promoting neovascularization in ischemic tissues. This experimental study evaluated the formation of new blood-vessels after omental implantation (OI) in rats after ligation of the hepatic artery. Wistar rats were used and divided into the following groups: I OI with HAL, II OI without HAL, III hepatic artery ligation (HAL). For angiography, measurements were made of liver tissue blood flow by the laser Doppler method and of hepatic artery flow by the colored microsphere method (CMS), and immunohistochemical study was done for vascular endothelial growth factor (VEGF). The rats were killed at 1, 3, 7 or 30 days after laparotomy. Relative arterial hepatic blood flow in the implanted lobe of group I, as determined by CMS, reached 50% of control values 7 days after surgery. Angiography and microscopic studies of the excised liver revealed distinct angiogenesis surrounding the omental implant in the liver for 7 days postoperatively. The formation of new blood-vessels after OI was not observed in livers without HAL. Omental implantation appears to be useful in preventing organ anoxia after hepatic artery thrombosis.

Animals↗

A non-toxic heat shock protein 70 inducer, geranylgeranylacetone, suppresses apoptosis of cultured rat hepatocytes caused by hydrogen peroxide and ethanol.

BACKGROUND/AIMS: A stress-inducible heat shock protein 70 (HSP70) is one of the best-known endogenous factors protecting cell injury under various pathological conditions. The aim of this study was to examine anti-apoptotic actions of a non-toxic HSP70 inducer, geranylgeranylacetone (GGA), on hepatocytes exposed to hydrogen peroxide (H2O2) or ethanol. METHODS: Primary cultures of rat hepatocytes were treated with different concentrations of GGA and exposed to 0.5 mM H202 or 100 mM ethanol. The heat shock response was assessed by measuring the activation of heat shock factor 1 (HSF1), HSP70 mRNA expression, and accumulations of HSP70, HSP90, and HSP27. Apoptosis was evaluated by DNA fragmentation. RESULTS: Pretreatment with 1 microM GGA for 2 h enhanced nuclear translocation and phosphorylation of HSF1, HSF1-DNA binding, HSP70 mRNA expression, and its accumulation, when the cells were exposed to H202 or ethanol. In association with this accelerated response, GGA suppressed the insult-induced activation of c-Jun N-terminal kinases, caspase 9, and caspase 3-like proteases, leading to significant inhibition of apoptosis. CONCLUSIONS: GGA exerted anti-apoptotic actions, at least in part, by priming hepatocytes for enhanced HSP70 induction. Our results suggest that GGA may have a potential benefit for the treatment of alcoholic and ischemia-reperfusion liver injuries.

Animals↗

Lymphatic spreading pattern of intrahepatic cholangiocarcinoma.

BACKGROUND: There have been very few reports on the pattern of lymphatic spread of intrahepatic cholangiocarcinoma. This pattern was elucidated to help define the rational extent of radical lymph node dissection. METHODS: Thirty-nine consecutive patients who underwent hepatectomy with radical lymph node dissection were reviewed retrospectively. RESULTS: Lymph node metastases were detected in 24 of the 39 patients (62%). The metastatic nodes were found in the hepatoduodenal ligament, along the common hepatic artery, around the abdominal aorta, on the posterior surface of the pancreas head, along the left gastric artery, along the superior mesenteric artery, around the celiac artery, along the lesser curvature of the stomach, and around the cardia. The nodal involvements along the left gastric artery, along the lesser curvature, or around the cardia were recognized only in the left peripheral and hilar types of cholangiocarcinoma, while all other sites included both the left or right peripheral type and the hilar type cholangiocarcinoma. CONCLUSIONS: Intrahepatic cholangiocarcinomas, irrespective of their intrahepatic location, mainly spread to the nodes in the hepatoduodenal ligament, then to the para-aortic nodes, retropancreatic nodes, or common hepatic artery nodes. In addition to these spreading routes, the left peripheral type or hilar type of cholangiocarcinoma tends to spread along the left gastric nodes through the lesser curvature.

Adult↗

[A case of successful management of nonresectable pancreas cancer with liver metastasis by intra-arterial infusion chemotherapy with angiotensin-II and administration of tegafur/uracil].

Nontypical chemotherapy regimens exist for advanced pancreatic cancer. We herein report a 62-year-old man whose nonresectable pancreatic cancer was treated effectively with a new method of intra-arterial regional chemotherapy with angiotensin-II (AT-II). The patient was admitted to our hospital with obstructive jaundice and anorexia. He was diagnosed as having inoperable advanced pancreatic cancer with liver metastasis. Enteric-coated tegafur/uracil (400 mg) was administered for 3 weeks. Simultaneously, intraarterial infusion with 5-fluorouracil (500 mg) and infusion of methotrexate (100 mg) with 50 micrograms of AT-II was given every week. A catheter connected to a subcutaneously implanted port system was placed into the common hepatic artery. As a result of this treatment, the maximum diameter of the pancreatic tumor decreased from 3 cm to 2 cm on the CT-scan. Serum carbohydrate antigen 19-9 (CA19-9) decreased from 24,000 U/ml to 186 U/ml. Moreover, the performance status of patient also improved, and he was discharged from our hospital despite his terminal cancer. This regimen could well be effective in cases of advanced pancreatic cancer.

Angiotensin II↗

[A case of nonresectable scirrhous type gastric cancer treated by hypertensive subselective chemotherapy with pharmacokinetic modulating chemotherapy].

There have been few effective chemotherapeutic regimens for scirrhous type gastric cancer. A 62-year-old male patient was admitted to our hospital because of anorexia and abdominal discomfort. Gastroendoscopy showed a type 4 advanced gastric cancer in the upper gastric body. Histologic study of biopsy specimens from the tumor revealed poorly differentiated adenocarcinoma. Examination by computed tomography and ultrasonography revealed swollen paraaortic lymph nodes and peritonitis carcinomatosa. The patient was diagnosed as having a nonresectable scirrhous type gastric cancer with peritonitis carcinomatosa and paraaortic lymph node metastasis. This patient was treated weekly with an intraarterial 5-FU (500 mg) and MTX (100 mg) including AT-II by a subcutaneously implanted port system placed into the thoracic aorta. Furthermore, he was administered tegafur/uracil (400 mg/day) 5 days weekly as a pharmacokinetic modulating chemotherapy (PMC). After eight courses of treatment of PMC, paraaortic lymph node swelling and ascites decreased. This chemotherapy produced a partial response in the peritonitis carcinomatosa and paraaortic lymph nodes. This chemotherapy was repeated preoperatively. We reconsidered this case to show indications for operation. The patient died suddenly of acute heart failure before the operation. This therapy was considered an effective treatment for nonresectable gastric cancer.

Adenocarcinoma, Scirrhous↗

Experimental study of combined treatment with tacrolimus and donor splenocytes via the portal vein in small bowel transplantation.

We previously reported that the combined treatment of perioperative administration of donor splenocytes via the recipient's portal vein (DSPV) and a short-course Tacrolimus significantly prolonged the survival of fully allogenic grafts in rat small bowel transplantation (SBTX). In the present study we examined whether this effect depended on the quantity of the administered alloantigens in DSPV. In addition, we examined the expression of the surface antigen on T cells of the splenocytes and the induced toleragenic factor, according to the tolerant recipients which in our previous report had shown the prolongation of allogenic transplant small bowel graft survival by the combined treatment of DSPV (1 x 10(8) donor splenocytes) and a short-course Tacrolimus. Donor splenocytes were prepared from Brown-Norway (BN (RT1n)) rat spleens for Lewis (LEW (RT1l)) recipients. The recipients (n = 10), treated with a short course of Tacrolimus (0.5 mg/kg, 0 to 3 days postoperatively) only showed graft rejection with an average of 6.3 +/- 1.0 days postoperatively. However, the combined treatment, consisting of DSPV of 1 x 10(8) donor splenocytes and a short course Tacrolimus significantly prolonged graft survival to 12.7 +/- 2.1 days (n = 12, P < 0.01). DSPV of less than 1 x 10(8) donor splenocytes (5 x 10(7) cells and 2.5 x 10(7)) could not prolong the graft or animal survival under a short-course Tacrolimus treatment. In the tolerant recipients, the CD4 and CD8 percentages of splenocytes were not significantly different from those of control rats or recipients that were treated with short-course Tacrolimus alone. Nevertheless, the percentage of Tcr-alpha beta+ cells expressing IL-2 receptor (R) was significantly lower than in either control rats or the recipients with short-course Tacrolimus. In the suppression assay to one-way mixed lymphocyte response, a toleragenic factor was suggested to the present in the serum of the tolerant recipients. In the present study, it was suggested that the effects of the combined treatment of DSPV and short-course Tacrolimus for the prolongation of graft survival in the rat allogenic SBTX should depended on the quantity of the antigens administered into the portal vein. The beneficial effects of this treatment were reflected in the suppression of IL-2R on the recipient's splenocytes, and tolerogenic factor(s) might subsequently be induced in the tolerant recipient's serum.

Animals↗

Rad51 accumulation at sites of DNA damage and in postreplicative chromatin.

Rad51, a eukaryotic RecA homologue, plays a central role in homologous recombinational repair of DNA double-strand breaks (DSBs) in yeast and is conserved from yeast to human. Rad51 shows punctuate nuclear localization in human cells, called Rad51 foci, typically during the S phase (Tashiro, S., N. Kotomura, A. Shinohara, K. Tanaka, K. Ueda, and N. Kamada. 1996. Oncogene. 12:2165-2170). However, the topological relationships that exist in human S phase nuclei between Rad51 foci and damaged chromatin have not been studied thus far. Here, we report on ultraviolet microirradiation experiments of small nuclear areas and on whole cell ultraviolet C (UVC) irradiation experiments performed with a human fibroblast cell line. Before UV irradiation, nuclear DNA was sensitized by the incorporation of halogenated thymidine analogues. These experiments demonstrate the redistribution of Rad51 to the selectively damaged, labeled chromatin. Rad51 recruitment takes place from Rad51 foci scattered throughout the nucleus of nonirradiated cells in S phase. We also demonstrate the preferential association of Rad51 foci with postreplicative chromatin in contrast to replicating chromatin using a double labeling procedure with halogenated thymidine analogues. This finding supports a role of Rad51 in recombinational repair processes of DNA damage present in postreplicative chromatin.

Bromodeoxyuridine↗

Transient expression of megakaryocyte-derived protein immunoreactive with an antiserum to cartilage oligomeric matrix protein in developing rat liver.

We analyzed a megakaryocyte-derived protein immunoreactive with an antiserum to cartilage oligomeric matrix protein (COMP) in the developing rat liver. Staining with the anti-COMP antiserum in the developing rat liver increased during embryogenesis, and was strongest in the livers of 17-day-old embryos. However, staining in the liver was not detected at eight days after birth or thereafter. The stained cells were found to be megakaryocytes. We partially purified the protein showing cross-reaction with the antiserum to COMP from a megakaryocyte-rich cells fraction in 17-day-old embrionic rat livers. The molecular weight of this protein (approximately 95 kDa) was close to the molecular weight of COMP (105 kDa). Amplification of an RT-PCR fragment (225 bp) corresponding to part of COMP mRNA was detected in cartilage, but not in megakaryocytes of fetal liver or bone marrow. Based on these results, the fetal rat liver megakaryocyte-derived protein that reacted with the antiserum against COMP was thought to contain a common epitope with COMP from cartilage, but to be a different protein from COMP.

Acetylcholinesterase↗

Hepatocellular carcinoma effectively treated by intravenous infusion of cisplatin.

We report a rare case of hepatocellular carcinoma (HCC) for which intravenous administration of cisplatin (CDDP) was effective. A 48-year-old woman with recurrent HCC was admitted to our hospital. She had undergone right hepatectomy 1 year previously. A large tumor in the liver and multiple lung metastases were found by computed tomography in June 1995. She was icteric, and titers of serum alpha-fetoprotein (AFP; 214 ng/ml) and protein induced vitamin K absence or antagonist-II (PIVKA-II; 80 AU/ml) were high. According to these findings, she was diagnosed as having nonresectable recurrent HCC with extrahepatic lesions. She was treated by intravenous administration of CDDP. The dose of CDDP was 50 mg and it was infused once a week. One kur of CDDP was 4 weeks, and a total of four kur were administered. We noted that the lung metastases and primary liver tumor resolved after 1 kur of chemotherapy. The levels of serum AFP and PIVKA-II decreased markedly, to 26 ng/ml and <0.07 AU/ml, respectively. A complete response was obtained, and she maintained a good state of health for the next 6 months, until brain metastases occurred. She died 13 months after the initiation of treatment with CDDP. In general, intravenous CDDP cannot be recommended as a single agent for HCC therapy, but CDDP showed good antineoplastic activity in our patient.

Antineoplastic Agents↗

Intraoperative microwave coagulation therapy for large hepatic tumors.

We report new surgical techniques for intraoperative microwave coagulation therapy (IMCT), conducted in three patients with large liver neoplasms with poor liver function or difficult tumor location. Anterolateral thoracotomy was performed for tumors in the right lobe to obtain a good operative field. Four electrode needles were inserted for microwave irradiation, with settings of 60 W, 45 s for coagulation and 1 s for dissociation. Clamping of the hepatoduodenal ligament was performed during IMCT. We began the coagulation at the bottom of the tumor, irradiating the tumor and the surrounding parenchyma to create regional necrosis with a safe margin. With these methods, we treated two women diagnosed with large hepatocellular carcinoma with liver cirrhosis and a man with liver metastasis from rectal cancer. The postoperative course of these patients was uneventful. A marked low-density area was seen in the region of therapy and no enhanced findings were observed on enhanced computed tomography postoperatively. However, in one patient, transcatheter embolization (TAE) was performed 1 month postoperatively because recurrence was noted on the bottom of the tumor. Thus, IMCT destroys the peripheral part of the tumor that may remain viable after TAE, but combination therapy with TAE is preferable, especially when a viable part exists within tumors. IMCT is an active, safe, and nontoxic therapeutic modality for large hepatic tumors, and is particularly applicable in patients with large hepatocellular carcinomas and poor liver function.

Aged↗

Expression of somatostatin receptor subtypes and growth inhibition in human exocrine pancreatic cancers.

The antiproliferative effects of somatostatin and its analogs on human pancreatic cancers were studied: (1) by evaluating the gene expression of somatostatin receptor (sstr) subtypes in human pancreatic cancer cell lines and cancer tissue specimens, (2) by evaluating the antiproliferative effects of somatostatin analogs, and (3) by evaluating the effect of sstr-2 cDNA transduction. Using a reverse transcriptase polymerase chain reaction (RT-PCR), the gene expression of five sstr subtypes (sstr-1 to -5) was examined in eight cell lines, and in ten pancreatic cancer tissues and in the normal surrounding pancreatic tissues. The antiproliferative effects of somatostatin (SS) -14 and its two analogs (SMS 201-995, RC-160) were examined by means of an MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (thiazolyl blue)) assay on three cell lines and Panc-1 transfectants with human sstr (hsstr)-2A cDNA. Sstr-2 was expressed in all samples tested. All examined cell lines simultaneously expressed sstr-2 and -5, while most of the examined pancreatic cancer tissues did not express both of these subtypes simultaneously. Somatostatin analogs inhibited epidermal growth factor (EGF)-stimulated pancreatic cancer cell proliferation. The cell proliferation was further and significantly inhibited by 14% in stable transfectants of Panc-1 cells with hsstr-2A. Based on these findings, it is concluded that somatostatin analogs with their antiproliferative effects mediated by sstr-2 could be potentially useful in the treatment of pancreatic cancers.

Cell Division↗

Effects of alendronate on bone metastases and hypercalcemia after surgery for hepatocellular carcinoma.

Alendronate, a bisphosphonate compound, lowers serum calcium in patients with cancer-associated hypercalcemia through its inhibitory effect on bone resorption and as a result symptoms associated with hypercalcemia improve. This study was carried out to investigate the effects of alendronate in patients with hypercalcemia due to bone metastasis of hepatocellular carcinoma (HCC). Two patients were evaluated. Their corrected serum calcium and alpha-fetoprotein (AFP) levels and their computed tomography (CT), bone scintigraphy and magnetic resonance imaging (MRI) findings were evaluated before and during alendronate treatment. After treatment, not only the corrected serum calcium levels but also AFP levels and bone pain decreased; in addition, the regression of the metastatic focus was noted in the MRI analysis. These tumor inhibitory effects of alendronate have not been reported in HCC before; and alendronate might serve to prevent bone metastases in patients with HCC. In conclusion, two patients who developed hypercalcemia associated with bone metastasis after surgery for HCC were treated with alendronate and they experienced alleviation of the pain due to bone metastasis, improvement of their quality of life and a marked decrease in AFP levels with tumor regression.

Aged↗