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K Shirabe

Publications and source records attributed to K Shirabe.

At least 37 records · Page 2Linked to original sources
PubMed2000

Expression and antitumor effects of TRAIL in human cholangiocarcinoma.

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)/Apo2L has been recently identified as important in promoting programmed cell death in breast and colon adenocarcinomas. In this study, we investigated the expression and therapeutic potential of TRAIL in cholangiocarcinoma, one of the most devastating human hepatic malignancies. Expression of TRAIL receptors was determined in 13 patients with resectable intrahepatic cholangiocarcinoma. Cellular effects of TRAIL in promoting apoptosis of human cholangiocarcinoma cells were analyzed after exposure to recombinant protein, as well as following transfection with a cDNA expression construct. In vivo effects of TRAIL on tumor growth were investigated after subcutaneous injection of cholangiocarcinoma cells into nude mice. Analysis of 13 clinical and tissue samples revealed that TRAIL receptors containing the death domain were present in all cholangiocarcinomas as well as paired normal hepatic tissues derived from surgically resected margins. In contrast, 7 tumors did not express the TRAIL decoy receptors lacking the death domain; such receptors were detectable in all of the normal hepatic tissue counterparts. Recombinant TRAIL induced extensive programmed cell death in cholangiocarcinoma cell lines lacking decoy receptor expression. Transfection of the ectodomain of TRAIL also induced cellular apoptosis; this effect was abolished by introduction of the generalized lymphoproliferative disease-like mutation in the TRAIL protein. Finally, in vivo administration of recombinant TRAIL substantially inhibited subcutaneous tumor growth of human cholangiocarcinoma cells. Induction of apoptosis in tumor cells is possible with a biologically active TRAIL, and suggests that this cytokine is a promising antitumor agent against human cholangiocarcinoma.

Amino Acid Sequence↗
PubMed2000

Infected hepatic cyst in a patient with multiple hepatic cysts: report of a case diagnosed by change of ultrasonographic findings.

Liver cysts are commonly observed, but infection of a liver cyst is a rare complication. Although patients have clinical symptoms, such as a high-grade fever and abdominal pain, diagnosing an infected cyst by abdominal ultrasonography, computed tomography (CT) with contrast medium and magnetic resonance imagings (MRI) is not always easy. We experienced an unusual case who had only clinical symptoms, such as high-grade fever and a right quadrant abdominal pain, but no imaging findings when admitted. Careful observation using ultrasonography once a week revealed signs of an infected cyst containing echogenic fluid 32 days after admission. We performed percutaneous transhepatic cystic drainage. When a patient has liver cysts and complains of high-grade fever and abdominal pain, liver cysts should be considered as a focus of sepsis, and we recommend repeat use of ultrasonography or CT, even if no typical findings occur the first time.

Aged↗
PubMed2000

The role of telomerase activity in hepatocellular carcinoma.

OBJECTIVE: The aim of this study was to clarify the role of telomerase activity in hepatocellular carcinoma (HCC). METHODS: Specimens from both HCC and noncancerous liver were obtained from 39 patients with HCC using a 14-gauge biopsy needle immediately after laparotomy. Telomerase activity was determined using a telomeric repeat amplification protocol assay. The 3+ of telomerase activity in HCC was defined as a high telomerase group, and 2+ or less of HCC telomerase activity was defined as a low telomerase group. In noncancerous liver, 2+ or more of telomerase activity was defined as an increased telomerase group, and 1+ or less of telomerase activity was defined as a nonincreased telomerase group. The correlation between telomerase activity in HCC or noncancerous liver and clinicopathological factors, including prognosis, was investigated. RESULTS: Telomerase activities in HCCs were 0 in one patient, 1+ in two, 2+ in seven, and 3+ in 29 patients. The disease-free survival rate in the high telomerase group was significantly worse than that in the low telomerase group. The des-gamma-carboxy prothrombin level in a high telomerase group (median, 330 mAU/ml) was significantly higher than that in the low telomerase group (median, 150 mAU/ml). A multivariate analysis revealed that higher TNM stage, high telomerase activity in HCC, female gender, and high alpha-fetoprotein value were independent significant factors related to be early recurrence. The incidence of multicentric HCC occurrence in the increased telomerase group (53.3%) tended to be higher than that in the nonincreased telomerase group (27.3%). CONCLUSION: A high telomerase activity in HCC correlated with the potential of HCC to be more malignant, which was expressed as both a high level of des-gamma-carboxy prothrombin and an earlier recurrence after hepatectomy than that of HCC with a low telomerase activity.

Adult↗
PubMed2000

Development of a hybrid artificial liver using a polyurethane foam/hepatocyte-spheroid packed-bed module.

Primary dog hepatocytes spontaneously formed spheroids in the pores of polyurethane foam (PUF) within 1-2 days of stationary culture. The spheroids, about 100-150 microm in diameter, partly attached to the surface and immobilized inside these pores. The lidocaine disappearance rate decreased to about 4 microg/10(5) viable cells/day for 10 days, while in the PUF/spheroid culture the rate was maintained at almost the initial level of 8 microg/10(5) viable cells/day for 10 days. Then, two scales of PUF packed-bed modules were designed. A small module (PUF volume; 14.5 cm3) was used for in vitro culture to investigate optimum culture conditions, and a large module (PUF volume; 300 cm3) was designed for dog experiments. Hepatocytes inoculated in these modules also formed spheroids and maintained almost the same activity of albumin secretion rate (111 microg/cm3 PUF/day in the small module and 87.7 microg/cm3 PUF/day in the large module). These results indicate that the PUF packed-bed module containing hepatocyte-spheroids is promising as a hybrid artificial liver.

Albumins↗
PubMed2000

Conditions required for a hybrid artificial liver support system using a PUF/hepatocyte-spheroid packed-bed module and it's use in dogs with liver failure.

We studied the effects of a hybrid artificial liver support system we developed on dogs with hepatic failure. The system consisted of a multi-channel polyurethane foam packed-bed culture module, including primary dog hepatocyte spheroids. Blood ammonia was well metabolized by 20 g hepatocytes, but the other functions such as glucose concentration, total bile acid concentration, and survival time required 30 g hepatocytes to improve conditions. We found that we should use a culture substratum that easily forms spheroids, and that an artificial liver module should be used as soon as possible after spheroid formation by hepatocytes in the module.

Animals↗
PubMed1999

Evaluation of a hybrid artificial liver using a polyurethane foam packed-Bed culture system in dogs.

BACKGROUND AND AIMS: We developed a polyurethane foam packed-bed culture system of hepatocyte spheroids as a hybrid artificial liver (PUF-HAL), which was effective for recovery from liver failure in rat experiments. In this report, the design of a scaled-up PUF-HAL for dogs is described and evaluated using a dog acute liver failure model. METHODS: Warm ischemic liver failure was induced with a portocaval shunt in each dog. The dogs were divided into two groups: (1) a control group (N = 4), in which each dog was attached to a PUF-HAL without hepatocytes for 9 h, and (2) a HAL group (N = 5), in which each dog was attached to a PUF-HAL with hepatocytes. Blood pressure, blood ammonia, blood glucose, serum creatinine, and other parameters related to liver function were compared between the two groups. RESULTS: In the HAL group, blood ammonia and serum creatinine levels were significantly lower, and blood pressure and blood glucose levels significantly higher, than those in the control group. CONCLUSIONS: The scaled-up PUF-HAL developed for large animals is useful as a liver support system in the dog acute liver failure model.

Ammonia↗
PubMed1999

CEPU-1, an immunoglobulin superfamily molecule, has cell adhesion activity and shows dynamic expression patterns in chick embryonic spinal cord.

In an attempt to isolate novel molecules involved in motoneuron differentiation and target muscle innervation during embryogenesis, we performed mRNA differential display analysis by comparing cDNAs of motoneurons purified by immunopanning from different portions along the rostro-caudal axis of chick embryonic spinal cord, and cloned an immunoglobulin superfamily protein named C30. By sequence comparison, C30 was shown to be an alternatively spliced isoform of CEPU-1, which was formerly reported as a member of the immunoglobulin superfamily specifically expressed in cerebellar Purkinje cells (Spaltmann and Brummendorf, 1996, J. Neurosci. 16, 1770-1779). We analyzed the expression pattern of CEPU-1 both at the mRNA and protein levels in the spinal cord of the chick embryo. Until stage 23, CEPU-1 was expressed faintly in the ventral part of the neural tube but gradually it became localized to a specific group of cells. In the motor column, CEPU-1 was expressed transiently in many columnar layers. A C30-transfected cell line showed Ca(2+)-independent cell-cell binding activity. These results suggest a role for CEPU-1 in specific axon guidance and/or fasciculation of motoneurons during development.

Animals↗
PubMed1999

Postoperative liver failure after major hepatic resection for hepatocellular carcinoma in the modern era with special reference to remnant liver volume.

BACKGROUND: Postoperative liver failure is a life-threatening complication after hepatic resection. Because of recent advances in liver surgery technique and a more stringent patient selection, mortality after hepatic resection has steadily decreased, but its incidence still ranges from 10% to 20%. The factors linked to postoperative liver failure in major hepatic resection in the modern era should be reevaluated. STUDY DESIGN: Of 80 patients with viral markers (hepatitis C viral antibody or hepatitis B surface antigen) who underwent major hepatic resections (no less than bisegmentectomies) for hepatocellular carcinoma between 1990 and 1996, 7 patients (8.8%) died of postoperative liver failure within 6 months after hepatectomy. The cause of liver failure was analyzed based on both the preoperative data and the intraoperative findings. In addition, since all the patients who died of liver failure underwent a right hepatic lobectomy, a further data analysis was also done in 47 patients who underwent a right lobectomy of the liver. A volumetric analysis by CT was then done to evaluate the remnant liver volume. RESULTS: Between the patients with liver failure and those without liver failure who underwent a right lobectomy, there were no significant differences in preoperative data or intraoperative findings. Volumetric analysis revealed that the remnant liver volume of patients who died of liver failure was significantly smaller than that of patients who lived (p = 0.008). The incidence of liver failure in patients with a remnant liver volume of less than 250 mL/m2 was 7 of 20 (38%), while it was 0 of 27 in patients with a liver volume of no less than 250 mL/m2 (p = 0.0012). The only significant risk factor for liver failure in patients with a remnant liver volume of less than 250 mL/m2 was diabetes mellitus (p = 0.0072). CONCLUSIONS: The expected remnant liver volume appears to be a good predictor for liver failure in patients who undergo a right lobectomy of the liver. In patients with diabetes mellitus and an expected remnant liver volume of less than 250 mL/m2, a major hepatectomy should be avoided. Careful patient selection based on volumetric analysis in major hepatectomy cases could help prevent the occurrence of postoperative liver failure.

Aged↗
PubMed1999

[Factors linked to 5-year survival after hepatectomy for hepatocellular carcinoma: univariate and multivariate analyses of 312 patients].

The purpose of this study was to clarify the factors linked to 5-year survival after hepatectomy for hepatocellular carcinoma (HCC). Three hundreds and twelve patients who underwent hepatectomy for HCC between 1985 and 1994 were observed for at least 5 years. These patients were divided into 2 groups: 160 patients who died within 5 years after hepatectomy and 152 patients who did not die within 5 years. Statistical analysis by chi 2 test showed that the favorable factors linked to 5-year survival were (a) diabetes mellitus (-), (b) albumin > 3.7 g/dl, (c) hepaplastin test > 61%, (d) indocyanine green retention test at 15 minutes < 16%, (e) curative resection (+), (f) alpha-fetoprotein < or = 32 ng/ml, (g) portal vein invasion (-), (h) intrahepatic metastasis (-), and (i) stage I and II. Statistical analysis by stepwise regression test showed that the favorable factors linked to 5-year survival were (a) intrahepatic metastasis (-), (b) diabetes mellitus, (c) indocyanine green retention test at 15 minutes < 16%, (d) curative resection (+) and (e) alpha-fetoprotein < or = 32 ng/ml. When patients diagnosed with HCC, patients selection for hepatectomy should be done, based on the total estimation, such as tumor invasiveness, liver functions, and diabetes mellitus.

Analysis of Variance↗
PubMed1999

Expression of matrix metalloproteinase-9 in surgically resected intrahepatic cholangiocarcinoma.

BACKGROUND: Matrix metalloproteinase-9 (MMP-9) has recently been reported to be related to cancer cell invasion. This study was performed to clarify the expression of MMP-9 in surgically resected intrahepatic cholangiocarcinoma (IHCC). METHODS: In 37 patients with IHCC who underwent a surgical resection, the expression of MMP-9 and the clinicopathologic characteristics of MMP-9-positive IHCC were investigated. The expression of MMP-9 was immunohistochemically detected in 16 (43%) of 37 IHCC. The patients were divided into MMP-9 (-) IHCC (n = 21), MMP-9 (+) IHCC (n = 12), and MMP-9 (++) IHCC (n = 4). RESULTS: The survival rate after surgical resection in patients with MMP-9 (-), (+), and (++) IHCC, was 66%, 39%, and 0% at one year, 50%, 32% and 0% at 3 years, respectively (P = .001). The incidence rate of lymph node metastasis was 6 (28%) of 21 in MMP-9 (-) patients, 7 (58%) of 12 in MMP-9 (+) patients and 4 (100%) of 4 in MMP-9 (++) patients. The incidence rate of lymph node metastasis increased in proportion to an increase in the expression of MMP-9 in IHCC (P = .02). Recurrence in the lymph node was more common in patients with MMP-9 (+) and (++) cancers than in those with MMP-9 (-) cancers. CONCLUSIONS: The expression of MMP-9 in IHCC was a prognostic factor related to lymph node metastasis.

Adult↗
PubMed1998

Clinicopathologic features of patients with hepatocellular carcinoma surviving >10 years after hepatic resection.

BACKGROUND: This study was performed to clarify the clinicopathologic features of hepatocellular carcinoma (HCC) patients surviving >10 years after hepatic resection. METHODS: Between January 1971 and April 1987, 142 patients underwent hepatic resection. Thirty-nine patients who died of surgical morbidity (surgical mortality rate: 27.5%) were excluded from this study. Among the 103 patients who survived and were observed for >10 years after surgery, 12 patients (11.7%) survived >10 years after hepatectomy. The surviving patients were divided into 2 groups: 10-year survivors (n = 12) and nonsurvivors (n = 91). A comparative study between the two groups was made. RESULTS: Preoperative liver function tests such as the indocyanine green retention test at 15 minutes and albumin levels showed that 10-year survivors had better liver function than nonsurvivors. With regard to virus markers, 5 of 12 patients (41.7%) were positive for hepatitis B surface antigen (HBs-Ag) and the incidence of hepatitis B virus-related HCC was significantly higher than in nonsurvivors (P = 0.020). The results also showed that 4 of 12 long term survivors had hepatitis C virus (HCV) antibody and 1 patient did not have any HCV antibody or HBs-Ag. In two other patients, the HCV antibody was not measured and HBs-Ag was negative. Among four patients with the HCV antibody, the serum HCV RNA concentration, measured by branched DNA probe assay, was <0.5 in 3 patients and 1.72 in 1 patient. Therefore, the HCV RNA concentration tended to be lower in 10-year survivors. Tumor recurrence occurred in 8 of the 10-year survivors. Solitary recurrence was observed in five patients whereas multiple recurrence was observed in three patients. All five patients with solitary recurrence underwent a second resection. CONCLUSIONS: Based on the results of the current study, good liver function, HBs-Ag positivity, and a low concentration of serum HCV RNA in HCV-related HCC should be considered potentially good predictors of a long term survival.

Adult↗
PubMed1998

Natural killer cell activity in patients with hepatocellular carcinoma: a new prognostic indicator after hepatectomy.

BACKGROUND: Natural cytotoxicity mediated by natural killer (NK) cells is believed to play an important role in host anticancer defense mechanisms. The aim of this study was to examine the prognostic significance of NK cell activity after hepatectomy in patients with hepatocellular carcinoma. METHODS: The NK cell activity in 210 patients with hepatocellular carcinoma was measured and evaluated in relation to clinicopathologic variables using univariate and multivariate analyses. RESULTS: The NK cell activity was decreased significantly in hepatocellular carcinoma patients compared with the control groups (P < 0.001). No correlation was observed between NK cell activity and the clinicopathologic variables. Multivariate analyses indicated that NK cell activity as well as intrahepatic metastases, platelet count, and serum albumin level were independent prognostic factors. CONCLUSIONS: This study suggests that the preoperative NK cell activity will help predict recurrence and prognosis after hepatectomy in patients with hepatocellular carcinoma.

Adult↗
PubMed1998

Role of carboxyl residues surrounding heme of human cytochrome b5 in the electrostatic interaction with NADH-cytochrome b5 reductase.

To identify the cytochrome b5 residues responsible for the electrostatic interaction with NADH-cytochrome b5 reductase (b5R), we prepared and characterized the cytochrome b5 mutants in which Glu41, Glu42, Glu63, Asp70, and Glu73 were replaced by Ala, utilizing site-directed mutagenesis and the expression system for cytochrome b5 in Escherichia coli. Apparent Km values of the wild type b5R for Glu42Ala cytochrome b5 and Asp70Ala cytochrome b5 were approximately three-fold and six-fold higher than that for the wild type cytochrome b5, respectively, while the kcat values for those mutants were not remarkably affected. In contrast, Glu41Ala, Glu63Ala, and Glu73Ala cytochrome b5 showed almost the same kinetic properties as the wild type cytochrome b5. Furthermore, kinetic studies on combinations of the cytochrome b5 and b5R mutants suggested the interaction between Glu42 and Asp70 of cytochrome b5 and Lys125 and Lys41 of b5R, respectively, in the reaction.

Amino Acid Substitution↗
PubMed1998

Electrostatic interaction between NADH-cytochrome b5 reductase and cytochrome b5 studied by site-directed mutagenesis.

Electrostatic interaction between NADH-cytochrome b5 reductase and cytochrome b5 was studied by site-directed mutagenesis. The target residues for mutagenesis were selected on the basis of the previously reported chemical cross-linking study of these two proteins, which implicated possible charge-pair interactions between Lys-41, Lys-125, Lys-162, and Lys-163 of the enzyme, and Glu-47, Glu-48, Glu-52, Glu-60, Asp-64 (group A), and heme propionate of cytochrome b5. Mutant reductases that lost one of the above-listed Lys residues showed higher K(m) values for cytochrome b5 and lower kcat values than those of the wild type, suggesting that all of the examined Lys residues participate in binding with cytochrome b5 as reported previously. In contrast, a removal of one of (or even all of) the group A residues from cytochrome b5 by mutagenesis caused no significant effect on the catalytic properties of cytochrome b5. Additional elimination of another set of negative residues (Glu-41, Glu-42, Asp-57, and Glu-63 (Group B)), which are also located close to heme, elevated the K(m) value by more than five folds. These results suggest that there should be other acidic residue(s) than group A in cytochrome b5 which participate in binding with NADH-cytochrome b5 reductase.

Binding Sites↗
PubMed1998

A thoracoabdominal hepatectomy and a transdiaphragmatic hepatectomy for patients with cirrhosis and hepatocellular carcinoma.

OBJECTIVE: To evaluate the results of a thoracoabdominal hepatectomy and a transdiaphragmatic hepatectomy for hepatocellular carcinoma in patients with impaired liver function. DESIGN: Retrospective study. SETTING: A university hospital in Japan. PATIENTS: Twenty-seven patients who from 1991 to 1996 underwent a thoracoabdominal hepatectomy for hepatocellular carcinoma located mainly in the superior portion of the liver and 20 patients who underwent a transdiaphragmatic hepatectomy for hepatocellular carcinoma located near the diaphragm. MAIN OUTCOME MEASURES: Morbidity, survival, and disease-free survival after each operation. Comparisons were then made with 183 patients who had undergone an ordinary transabdominal hepatectomy during the same period. RESULTS: In the thoracoabdominal hepatectomy group, 17 patients underwent a partial resection, 4 patients underwent a subsegmentectomy, and another 6 patients underwent either a segmentectomy or a procedure that was greater in size than a segmentectomy, whereas all of the patients in the transdiaphragmatic group underwent a partial resection. The morbidities in the thoracoabdominal group included pleural effusion in 6 patients (22%); intra-abdominal infection in 5 patients (19%); and hepatic failure in 3 patients (11%), of whom 1 died (mortality rate, 4%). In the transdiaphragmatic group, only 2 patients (10%) had non-life-threatening complications. The cumulative survival rates and the disease-free survival rates of the patients at 3 years were 51% and 24% in the thoracoabdominal hepatectomy group and 62% and 30% in the transdiaphragmatic hepatectomy group; no significant differences were observed when these findings were compared with those of patients who had undergone a transabdominal hepatectomy. CONCLUSION: The outcomes of the patients undergoing thoracoabdominal hepatectomy and those undergoing a transdiaphragmatic hepatectomy were generally satisfactory in spite of the fact that these procedures were performed on patients with cirrhosis and impaired liver function.

Aged↗
PubMed1998

Treatment strategy for patients with cystic lesions mimicking a liver tumor: a recent 10-year surgical experience in Japan.

OBJECTIVE: To clarify some of the difficulties in determining the appropriate surgical indications for cystic lesions mimicking a neoplasm in the liver. DESIGN: A retrospective review of hepatic resections for cystic lesions mimicking a neoplasm in the liver between August 1, 1986, and July 31, 1996. SETTING: A university hospital with a long history of hepatic resection for cystic lesions mimicking a neoplasm in the liver. PATIENTS: Ten patients with such cystic lesions in the liver, who underwent a hepatectomy during a recent 10-year period, were included in this study. MAIN OUTCOME MEASURES: Detailed clinicopathologic data were analyzed, and comparisons were made between the preoperative and postoperative diagnoses. RESULTS: The postoperative diagnoses consisted of cysts, including cysts complicated by an infection or hemorrhage in 7 patients, localized cystic dilation of the bile duct due to hepatolithiasis in 1, cystadenoma in 1, and mucin-producing cholangiocarcinoma in 1. In only one case was postoperative diagnosis identical to the preoperative diagnosis. In one case, an intraoperative pathological examination showed the tumor to be a mucin-producing cholangiocarcinoma instead of a cystadenocarcinoma. A tumor-marker analysis of the fluid in the cystic lesions also did not contribute to a definite diagnosis. Furthermore, cytological examination of the fluid could not completely exclude malignancy. Neither mortality nor morbidity occurred in any of the patients, and their mean length of hospitalization after hepatectomy was only 13.7 days. CONCLUSIONS: The accurate diagnosis of cystic lesions mimicking a tumor remains problematic; however, the results of hepatectomy for such cases are normally satisfactory. Such cystic lesions of the liver should be indicated for hepatectomy whenever the possibility of a cancerous neoplasm cannot be completely ruled out.

Adult↗
PubMed1998

Prognosis of hepatocellular carcinoma with diabetes mellitus after hepatic resection.

We evaluated the effect of diabetes mellitus on the prognosis of hepatocellular carcinoma after an elective hepatic resection. Of the 342 patients who underwent a hepatic resection between April 1985 and March 1995, 87 (25.4%) were diabetic. Postoperative morbidity was more common among diabetics than among nondiabetics (36.0% vs. 22.5%, P = .0239). The postoperative survival rate and the cancer-free survival rate were also better in patients without diabetes than in those with diabetes (P = .0333, P = .0149). The results of a multivariate analysis show diabetes mellitus to be an independent and prognostic indicator after a hepatic resection with hepatocellular carcinoma. According to the above findings, diabetes mellitus is thus considered to be a risk factor for prognosis after hepatic resection in patients with hepatocellular carcinoma.

Adult↗