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Yuji Nimura

Publications and source records attributed to Yuji Nimura.

At least 91 records · Page 5Linked to original sources
PubMed2003

A novel mitochondrial carnitine-acylcarnitine translocase induced by partial hepatectomy and fasting.

The carnitine-dependent transport of long-chain fatty acids is essential for fatty acid catabolism. In this system, the fatty acid moiety of acyl-CoA is transferred enzymatically to carnitine, and the resultant product, acylcarnitine, is imported into the mitochondrial matrix through a transporter named carnitine-acylcarnitine translocase (CACT). Here we report a novel mammalian protein homologous to CACT. The protein, designated as CACL (CACT-like), is localized to the mitochondria and has palmitoylcarnitine transporting activity. The tissue distribution of CACL is similar to that of CACT; both are expressed at a higher level in tissues using fatty acids as fuels, except in the brain, where only CACL is expressed. In addition, CACL is induced by partial hepatectomy or fasting. Thus, CACL may play an important role cooperatively with its homologue CACT in a stress-induced change of lipid metabolism, and may be specialized for the metabolism of a distinct class of fatty acids involved in brain function.

3T3 Cells↗
PubMed2003

Simultaneous segmental obstruction of bile duct and portal vein markedly changes a population of biliary and hepatic cells in human liver.

BACKGROUND AND AIMS: No studies have investigated histologic changes caused by simultaneous segmental obstruction of the bile duct and portal vein in human liver. PATIENTS/METHODS: Liver tissues with simultaneous obstruction of the segmental bile duct and portal vein (O(+/+) liver), with segmental bile duct obstruction alone (O(+/-) liver), and without obstruction (O(-/-) liver) were obtained from patients who underwent hepatectomy, and studied morphologically and immunohistochemically. RESULTS: In O(+/+) liver, the proportional area consisting of hepatocytes was significantly less (31.0+/-25.8%) than in O(+/-) liver (78.4+/-18.9%) or O(-/-) liver (86.5+/-9.2%). In contrast, the proportional area consisting of biliary epithelial cells was significantly higher in O(+/+) liver (9.1+/-6.1%) than in O(+/-) liver (1.6+/-1.5%) or O(-/-) liver (0.7+/-0.6%). The proportional area consisting of fibrous tissue also was significantly higher in O(+/+) liver than in the other two groups. In O(+/+) liver, some cells located at the periphery of hepatocyte areas were immunoreactive for both hepatocyte and biliary epithelial cell markers. CONCLUSION: Simultaneous segmental obstruction of the bile duct and portal vein induces a marked ductular increase, periportal fibrosis, and a reduction in the number of hepatocytes in human liver tissue.

Bile Duct Neoplasms↗
PubMed2003

Loss of p27(Kip1) accelerates DNA replication after partial hepatectomy in mice.

BACKGROUND: Liver regeneration after partial hepatectomy (PH) is accomplished by a synchronous replication of hepatocytes. Both positive and negative regulators of cyclin-dependent protein kinase (Cdk) have been implicated in hepatocyte proliferation, but their specific roles in vivo remain to be clarified. To investigate the specific role of p27(Kip1), a member of the Cip/Kip family of Cdk inhibitors, in cell-cycle regulation during liver regeneration, p27-knockout mice were studied after PH. MATERIALS AND METHODS: Under ether anesthesia, mice were subjected to 70% PH. Animals were sacrificed at intervals after the surgery, and the remnant liver was harvested and analyzed. RESULTS: In p27-deficient mice, the timing of DNA synthesis was significantly accelerated with a perturbation in the ordered distribution of proliferating cells in the hepatic lobule. p27 deficiency, however, did not affect the whole population of cycling cells, the number of apoptotic cells, or liver injury and mortality after PH. CONCLUSION: These data provide in vivo evidence that p27 functions as a brake in the "start" of the hepatocyte cell cycle, thereby coordinating temporally and spatially the onset of DNA synthesis of hepatocytes within the hepatic lobules.

Animals↗
PubMed2003

Diagnosis and treatment of inferior vena caval invasion by hepatic cancer.

Hepatectomy with concomitant resection of the inferior vena cava (IVC) has become common for hepatic malignancies involving the IVC. However, diagnosing IVC invasion and the procedure of choice have yet to be standardized. Medical records of nine patients with liver cancer (five metastatic tumors from colorectal cancer and four intrahepatic cholangiocarcinomas) believed to have directly invaded the IVC wall were retrospectively abstracted for data on preoperative radiologic studies, surgical procedures, histology of the resected specimen, and treatment outcome. All nine patients underwent hepatectomy: Five did not undergo IVC resection because the IVC could be isolated from the tumor; the remaining four underwent combined IVC resection (wedge and segmental resections in two each). The segmentally resected IVC was reconstructed using an external iliac vein graft. Total hepatic vascular exclusion, venovenous bypass, and the ex vivo technique were not used. Interestingly, the tumor was smaller and the percentage of the IVC circumference in contact with tumor as seen on computed tomography (CT) was less in patients with IVC invasion than in those without it (40 +/- 11 vs. 134 +/- 61 mm, p < 0.05; 30% +/- 8% vs. 60% +/- 20%, p < 0.05). The length of the IVC compressed by tumor on cavography was similar in the two patient groups (47 +/- 9 vs. 55 +/- 8 mm). All patients were discharged from the hospital in good condition: Seven died of cancer recurrence, and the remaining two are currently alive and disease-free 15 and 73 months after surgery, respectively. In conclusion, imaging modalities demonstrating caval deformation, such as CT and cavography, are unreliable for diagnosing direct invasion of the IVC wall. Even when IVC invasion is strongly suggested by conventional radiologic studies, the surgeon should endeavor to peel the tumor from the IVC. This strategy is important to avoid unnecessary resection of the IVC, use of a prosthetic graft, or ex vivo hepatectomy.

Adenocarcinoma↗
PubMed2003

A novel platinum compound inhibits telomerase activity in vitro and reduces telomere length in a human hepatoma cell line.

Telomerase activity is detectable in most human tumors but not in most normal somatic cells or tissues. Telomerase inhibition has, therefore, been proposed as a novel and potentially selective strategy for antitumor therapy. In the present study, we found that platinum compounds, including cisplatin [cis-diamminedichloro-platinum (II)], strongly inhibited the activity of partially purified rat telomerase. Among the agents tested, 2,3-dibromosuccinato [2-(methylaminomethyl)pyridine]platinum (II) (compound E) exhibited the strongest inhibition, with an median inhibitory concentration (IC(50)) of 0.8 micro M. The mode of inhibition was noncompetitive with either dNTPs or TS (first) primer, with K(i) values estimated to be 2.3 or 3.9 micro M for varied TS primer or dNTPs, respectively. Notably, cisplatin also inhibited the telomerase activity, with an IC(50) of 2.0 micro M. Again, the mode of inhibition was noncompetitive, with K(i) values estimated as 7.3 or 8.1 micro M. Preincubation of TS primer with compound E did not affect the telomerase inhibition, whereas preincubation with cisplatin caused remarkable enhancement. Treatment of a human hepatoma cell line HepG2 with a low concentration of compound E gradually reduced the telomere length, indicating that this compound was able to inhibit telomerase in living cells as well as in vitro.

Animals↗
PubMed2003

Overexpression of interleukin-15 protects against Escherichia coli-induced shock accompanied by inhibition of tumor necrosis factor-alpha-induced apoptosis.

Interleukin (IL)-15, a potent inhibitor of tumor necrosis factor (TNF)-alpha-mediated apoptosis, causes multiple organ failure during endotoxic shock. We investigated the potential role of IL-15 in protection against Escherichia coli-induced shock by using IL-15 transgenic (Tg) mice. These mice were resistant to an otherwise lethal challenge with E. coli, although bacterial burden and serum levels of TNF-alpha were similar in non-Tg mice. Apoptosis in cells of the peritoneal cavity, liver, spleen, or lung was significantly suppressed in IL-15 Tg mice after E. coli infection. Peritoneal cells from naive IL-15 Tg mice were also resistant to TNF-alpha-induced apoptosis in vitro, and neutralization of endogenous IL-15 significantly aggravated TNF-alpha-induced apoptosis. Exogenous IL-15 prevented TNF-alpha-induced apoptosis in normal mice in vitro and improved the survival rate after E. coli challenge. These results suggest that IL-15 overexpression can prevent TNF-alpha-induced apoptosis and protect against E. coli-induced shock, indicating a possible therapeutic application of IL-15 for septic shock.

Animals↗
PubMed2003

Clinicoanatomical studies on the dorsal subsegmental bile duct of the right anterior superior segment of the human liver.

BACKGROUND: The dorsal subsegmental intrahepatic bile duct in the right anterior superior segment (B8c) sometimes joins the posterior sectorial duct. In such cases it can be misidentified as the right posterior superior segmental duct (B7). However, there are no published studies on the confluent pattern of B8c. MATERIALS AND METHODS: We studied B8c in the resected liver of 107 patients (65 with bile duct carcinoma and 42 with gallbladder carcinoma) who had undergone right hepatectomy or more extensive right-sided liver resection. RESULTS: B8c was identified in all cases. It joined the right posterior sectorial duct or B7 in 18 cases (16.8%). In 12 cases B8c joined independently the posterior sectorial duct or B7. In 6 cases B8c joined the posterior sectorial duct after making the common duct with the lateral subsegmental duct in the anterior superior or anterior inferior segment (B8b or B5c). CONCLUSIONS: B8c does not join the anterior sectorial bile duct in every sixth case.

Aged↗
PubMed2003

Factors influencing postoperative hospital mortality and long-term survival after radical resection for stage IV gallbladder carcinoma.

Factors influencing postoperative hospital mortality and long-term survival after radical resection of stage IV gallbladder carcinoma remain unclear. The objective of this study was to identify characteristics of patients who are good candidates in terms of surgical risk and long-term survival for radical resection of stage IV gallbladder carcinoma. A retrospective study was made of attempted surgical cure in 72 patients with stage IV gallbladder carcinoma. There were 14 postoperative hospital deaths (19%). Eleven (19%) of the 58 patients discharged from hospital survived for more than 3 years. Multivariate analysis indicated male gender, extended right hepatic lobectomy in a cholestatic liver, and portal vein resection as independent risk factors that correlated with hospital death. Distant metastasis was the sole independent factor that related negatively with long-term survival by multivariate analysis. Subset analysis was performed with combinations of the four independent factors obtained by multivariate analyses. The hospital mortality rate and the 3-year survival rate in the 44 patients without portal vein involvement were 9% and 28%, respectively, and were 3% and 27%, for the 31 women in this group. The highest 3-year survival rate (39%) was observed in the 26 patients without distant metastasis and portal vein involvement, despite a hospital mortality rate of 12%. Better patient selection may improve the outcome of radical surgery for stage IV gallbladder carcinoma. These data may be useful in designing future trials of the surgical treatment of advanced gallbladder carcinoma.

Aged↗
PubMed2003

Effect of chitosan film containing basic fibroblast growth factor on wound healing in genetically diabetic mice.

Basic fibroblast growth factor (bFGF) has been shown to stimulate wound healing. However, consistent delivery of bFGF has been problematic. We studied the stability of bFGF incorporated into a chitosan film as a delivery vehicle for providing sustained release of bFGF. The therapeutic effect of this system on wound healing in genetically diabetic mice was determined as a model for treating clinically impaired wound healing. A chitosan film was prepared by freeze-drying hydroxypropylchitosan (a water-soluble derivative of chitosan) acetate buffer solution. Growth factor was incorporated into films before drying by mixing bFGF solution with the hydroxypropylchitosan solution. bFGF activity remained stable for 21 days at 5 degrees C, and 86.2% of activity remained with storage at 25 degrees C. Full-thickness wounds were created on the backs of diabetic mice, and chitosan film or bFGF-chitosan film was applied to the wound. The wound was smaller in after 5 days in both groups, but the wound was smaller on day 20 only in the bFGF-chitosan group. Proliferation of fibroblasts and an increase in the number of capillaries were observed in both groups, but granulation tissue was more abundant in the bFGF-chitosan group. These results suggest that chitosan itself facilitates wound repair and that bFGF incorporated into chitosan film is a stabile delivery vehicle for accelerating wound healing.

Animals↗
PubMed2003

NK T cells stimulated with a ligand for TLR2 at least partly contribute to liver injury caused by Escherichia coli infection in mice.

Fas ligand (Fas L) expression was induced on intrahepatic NK1.1(+) T cells in vivo after an intraperitoneal inoculation of Escherichia coli. Liver injury after E. coli infection, as assessed by serum GPT level and histological examination, was significantly reduced in Jalpha281(-/-) mice lacking NK1.1(+) T cells or in gld/gld mice bearing mutated Fas L, indicating that NK T cells at least partly contribute to E. coli-induced liver injury in a Fas/Fas L-dependent manner. Bacterial numbers in organs and cytokine levels in serum of Jalpha281(-/-) mice did not differ from those of Jalpha281(+/+) mice following E. coli infection. Intrahepatic NK1.1(+) T cells, which preferentially expressed Toll-like receptor 2 (TLR2) mRNA, responded in vitro to synthetic lipoprotein, a ligand for TLR2, by inducing Fas L expression on their surface. In a manner analogous to E. coli infection, lipoprotein and LPS could additively induce Fas L expression on NK1.1(+) T cells, leading to liver injury in vivo in normal mice but not in gld/gld mice. In conclusion, it is suggested that induction of Fas L on NK T cells in response to bacterial components such as lipoproteins plays an important role in pathogenesis of E. coli-induced liver injury in mice.

Animals↗
PubMed2003

Mucocele-like tumor of the breast caused by ductal carcinoma in situ: a case report.

A mucocele-like tumor (MLT) of the breast caused by clinging and micropapillary carcinoma in situ is reported. The tumor was a smooth-contoured mass located near the nipple in the lower inner quadrant of the left breast. Ultrasonography showed a cystic tumor and distended ducts. An aspiration specimen contained abundant mucinous material and a small amount of epithelial cell components, but was insufficient for cytological diagnosis. An excisional biopsy specimen disclosed multiple cysts containing mucin with extravasation into the stroma. Additional pathologic diagnosis using consecutive microscopic sections demonstrated ductal carcinoma in situ. Subcutaneous mastectomy was subsequently performed. Histopathologic findings in the resected and biopsy specimens indicated a diagnosis of MLT caused by widely spreading clinging and micropapillary ductal carcinoma in situ. The ductal epithelium of the MLT in an open biopsy specimen must be carefully examined using consecutive microscopic sections to detect occult DCIS.

Adult↗
PubMed2003

Most informative projection for portography: quantitative analysis of 47 percutaneous transhepatic portograms.

The goal of this study was to determine which projection for percutaneous transhepatic portography best depicts the anatomy of the proximal portal vein. Portograms ( n = 47) obtained in the anteroposterior, right anterior oblique, and right anterior caudal oblique projections were analyzed retrospectively. Lengths of the right portal trunk, the transverse portion of the left portal vein, and the right anterior and posterior portal branches, as well as angles between the right portal trunk and the transverse portion of the left portal vein and between the right anterior and posterior portal branches were measured in the various projections. Differences were evaluated using analysis of variance with Scheffe's method. The transverse portion of the left portal vein and the right anterior and posterior portal branches appeared longer on the right anterior caudal oblique views than on the anteroposterior ( p < 0.0001, < 0.0001, < 0.0001) or right anterior oblique ( p < 0.0001, = 0.001, < 0.0001) views. The angle between the right portal trunk and the transverse portion of the left portal vein was wider on the right anterior oblique views than on the anteroposterior ( p < 0.0001) or right anterior caudal oblique ( p = 0.007) views. The angle between the right anterior and posterior portal branches was wider on the right anterior caudal oblique views than on the anteroposterior ( p < 0.0001) or right anterior oblique ( p = 0.030) views. The right anterior caudal oblique projection provides the best image of the proximal portal vein, and therefore should be obtained whenever possible in preoperative staging of hepatobiliary cancer.

Humans↗
PubMed2003

Intrahepatic segmental bile duct patterns in hepatolithiasis: a comparative cholangiographic study between Taiwan and Japan.

BACKGROUND/PURPOSE: We analyzed confluence patterns of intrahepatic segmental bile ducts, seeking to relate hepato-lithiasis to anatomic variation. The comparative study was completed patients with hepatolithiasis in Taiwan and Japan. METHODS: Direct cholangiography was performed in 103 hepatolithiasis patients in Taiwan and 77 in Japan. Segmental ducts patterns were classified as type I, normal configuration; type II, "triad" confluence; type III, posterior segmental duct joining left hepatic duct; or type IV, distal confluence of the right posterior segmental duct. RESULTS: Taiwanese patients had only calcium bilirubinate or black stones, and were mostly female. As overall analysis, types I, II, III, and IV were found in 61, 26, 13, and 3 patients, respectively. In Japanese, types I, II, III, and IV were found in 52, 10, 13, and 2, respectively. There was no difference between the two institutes. Since no patients in Taiwan had cholesterol calculi, Japanese patients were reanalyzed including only 58 patients with calcium bilirubinate or black stones. Differences in those populations remained insignificant. CONCLUSION: Anatomic variations in segmental ducts apparently do not contribute to pathogenesis of hepatolithiasis.

Adolescent↗
PubMed2003

Expression of deleted in malignant brain tumor-1 (DMBT1) molecule in biliary epithelium is augmented in hepatolithiasis: possible participation in lithogenesis.

Deleted in malignant brain tumor-1 (DMBT1) is a mucin-like molecule participating in mucosal immune defense. Given that bovine gallbladder mucin, which accelerates cholesterol crystallization, is a DMBT1 homolog, DMBT1 expression was examined immunohistochemically in biliary epithelial cells in livers with hepatolithiasis (N = 25), primary sclerosing cholangitis (N = 7), large bile duct obstruction (N = 12), and control normal livers (N = 10). DMBT1 protein was determined in the hepatic bile samples of hepatolithiasis (N = 12) and other hepatobiliary diseases (N = 8) by immunoblot. While DMBT1 was faintly expressed in normal livers (20%), it was significantly augmented in hepatolithiasis (76%) (P < 0.05). DMBT1 was mildly expressed in primary sclerosing cholangitis and large bile duct obstruction. DMBT1 protein was detected frequently in hepatic bile samples of hepatolithiasis (50%) (P < 0.05), but in the other bile samples. The percentage of cholesterol in intrahepatic calculi was significantly higher in the patients with DMBT1-positive bile. Augmented expression and secretion of DMBT1 in intrahepatic large bile ducts in hepatolithiasis suggests its role in lithogenesis.

Agglutinins↗
PubMed2003

Proliferation kinetics and apoptosis of serrated adenoma of the colorectum.

To elucidate the proliferation kinetics and cell loss by apoptosis of serrated adenoma (SA) of the colorectum, we performed Ki-67 immunohistochemistry and the terminal deoxynucleotidyl transferase (TdT)-mediated biotinylated deoxyuridine-triphosphate nick-end labeling (TUNEL) method for 24 SA, and compared the results to those of normal colonic mucosa (n = 15), hyperplastic polyp (HP) (n = 18) and traditional tubular adenoma (TA) (n = 55). The growth fraction (Ki-67 labeling index) of SA was 18.8%, which was significantly lower than those of TA (40.1%) and HP (23.8%), while the apoptotic index of SA (0.14%) was significantly lower than that of TA (1.17%). The proliferative compartment in SA was distributed either basally (47%, 60/117 crypts), or in the intermediate portion (51.3%, 55/117 crypts), and there was no superficial translocation of the proliferative compartment, which was seen in 81.2% (361/445 crypts) of TA crypts. These results indicate that SA is a tumor with low proliferative activity and its growth would be maintained by a low extent of cell loss by apoptosis. The results also indicate the neoplastic process in SA is characterized by the disorder of cell migration, maturation and exfoliation similar to HP, and its epithelial cell maturation and migration occasionally occur bidirectionally, toward the surface and to the bottom of the crypt.

Adenoma↗
PubMed2003

Biliary bile acid concentration is a simple and reliable indicator for liver function after hepatobiliary resection for biliary cancer.

BACKGROUND: The functional recovery of the remnant liver after an extended hepatectomy is critical for the outcome of the patient. The aim of this prospective study was to examine whether biliary bile acids could be an indicator for postoperative liver function. METHODS: Externally drained bile samples were obtained from 51 patients with biliary or periampullary carcinomas before and after surgery. Patients were categorized into 3 groups: group A, 29 hepatectomized patients without liver failure; group B, 7 hepatectomized patients with liver failure (maximum serum bilirubin level, >10 mg/dL); and group C, 15 patients who underwent biliopancreatic resection without hepatectomy, with a good postoperative course. Bile samples were withdrawn 1 day before surgery and on postoperative days 1, 2, 3, 4, 6, and 7. Total bile acids were measured with a 3 alpha-hydroxysteroid dehydrogenase method. RESULTS: Before surgery, the concentration of bile acids was higher in groups A and C than in group B, and correlated significantly with the indocyamine green disappearance rate (KICG) values (R(2) = 0.557; P <.0001). After surgery, bile acid concentrations decreased in all 3 groups until postoperative day 2, which was followed by a gradual increase. The concentration recovered to the preoperative level in groups A and C but remained low in group B. Biliary bile acid concentrations on day 2 correlated significantly with remnant liver KICG values (R(2) = 0.257; P =.0019). Among several parameters studied, including KICG, remnant liver KICG, biliary bile acids, and biliary bilirubin, biliary bile acid concentration had the most predictive power for occurrence of postoperative liver failure. CONCLUSION: Biliary bile acid concentration could be a simple, real-time, reliable indicator of preoperative and postoperative liver function.

Aged↗