Biomedical subjects

H Yoshiji

Publications and source records attributed to H Yoshiji.

62 records · Page 4Linked to original sources

PubMed1990

Influence of timing of administration of liposome-encapsulated superoxide dismutase on its prevention of acetaminophen-induced liver cell necrosis in rats.

The possible participation of acute oxidative stress in the in vivo mechanism by which acetaminophen (APAP) induces hepatocellular injury was examined. Male Sprague-Dawley rats were administered 3-methylcholanthrene, fasted for 18 h, then given APAP and sacrificed after a further 6 h of fasting. Extensive centrilobular liver cell necrosis along with markedly elevated serum activity of aminotransferases was observed. Liposome-encapsulated human recombinant Cu-Zn superoxide dismutase (LSOD) administered 1 or 0.5 h prior to APAP or simultaneously with the toxin completely prevented APAP-induced hepatocellular injury. In contrast, LSOD administered 5 or 2.5 h before or 1, 2.5 or 5 h after the toxin treatment did not prevent APAP toxicity. Incomplete protection against APAP-induced injury was obtained when LSOD was administered 0.5 h after the toxin. These results support the proposal of an oxidative mechanism for APAP hepatotoxicity.

Acetaminophen↗

PubMed1990

Liposome-encapsulated superoxide dismutase prevents liver necrosis induced by acetaminophen.

Liposome-encapsulated human recombinant superoxide dismutase (LSOD) protected male rats that were pretreated with 3-methylcholanthrene from the liver necrosis produced by acetaminophen. By contrast, SOD-free liposomes, free SOD, or heat-denatured LSOD had no protective effect. Liposome-encapsulated SOD did not simply delay the onset of liver necrosis. A second dose of LSOD at 12 hours prevented the necrosis of the liver as assessed 24 hours after treatment with 500 mg/kg body weight of acetaminophen. Liposome-encapsulated human recombinant superoxide dismutase did not alter the metabolism of acetaminophen as assessed by either the rate or extent of the depletion of hepatic stores of glutathione or by the extent of the covalent binding of the metabolites of [3H]acetaminophen to total liver cell proteins. Evidence of the peroxidation of lipids in the accumulation of malondialdehyde in the livers was detected within 3 hours of the administration of acetaminophen and before the appearance of liver necrosis. Liposome-encapsulated human recombinant superoxide dismutase prevented the accumulation of malondialdehyde in parallel with the prevention of liver necrosis. Finally, LSOD also prevented the potentiation by 1,3-bis(2-chloroethyl)-1-nitrosourea of the hepatotoxicity of acetaminophen. These data document the participation of superoxide anions in the hepatotoxicity of acetaminophen in intact rats.

Acetaminophen↗

PubMedDate not supplied

Pancreatic pleural effusion with a pancreaticopleural fistula diagnosed by magnetic resonance cholangiopancreatography and cured by somatostatin analogue treatment.

A 69-year-old man with chronic alcoholic pancreatitis developed a left-sided massive pleural effusion. Magnetic resonance cholangiopancreatography clearly demonstrated the pancreatic cyst and the fistula connecting the cyst with the left pleural cavity, resulting in the diagnosis of pancreatic pleural effusion with a pancreaticopleural fistula. Conservative somatostatin analogue treatment completely eradicated the pancreatic pleural effusion and closed the pancreaticopleural fistula.

Aged↗

PubMedDate not supplied

Histopathological findings in a highly invasive mouse mammary carcinoma transfected with human tissue inhibitor of metalloproteinases-1.

We have transfected a full-lenght cDNA-encoding human tissue inhibitor of metalloproteinases-1 (TIMP-1) by lipofection in highly invasive F3II mouse mammary sarcomatoid carcinoma cells. In vitro, overexpression of TIMP-1 was associated with abrogation of metalloproteinase activity, extended doubling time, and a more flattened, epithelioid polyhedric morphology. Female Balb/c mice inoculated subcutaneously with TIMP-1 transfectant exhibited a prolonged tumor latency and tumor burden was significantly lower in early stages of tumor growth. Control F3II cells grew by invading the muscular and adipose layers of the subcutis, dermis, and dermal papillae. On the contrary, mammary carcinoma cells transfected with TIMP-1 grew without signs of active invasion of dermis. Tumors also revealed a decreased amount of necrosis and host inflammatory cell infiltrates. However, histological analysis did not demonstrate any change in vascular density. Animals bearing F3II tumors overexpressing TIMP-1 showed a significant reduction in the size of metastatic lung nodules. These data suggested that TIMP-1 overexpression may reduce local invasion and delay the progression of the metastatic disease in the present mammary tumor model.

Animals↗

PubMedDate not supplied

Sonographic estimation of liver tumor development induced by oral administration of thioacetamide in rat.

Animal models for various types of cancer are of great help in the study of tumors and antitumor effects. Subcutaneous models have been widely utilized because they can be produced easily by subcutaneously implanting tumor cells into animals. Although subcutaneous models are very convenient for examining tumor development, they are definitely different from clinical manifestations of original tumors. In orthotopic animal models for internal tumors, however, it is difficult to examine tumor development without sacrificing animals. We demonstrate here that the occurrence and growth of liver tumors induced by oral administration of thioacetamide into rats were clearly observable by ultrasonography, and that the sonographic estimation was accurate. It was observed sonographically that the number and volume of liver tumors increased proportionately with TAA treatment periods. These results indicate that sonography is a useful and non-invasive method to investigate liver tumor development in rats.

Administration, Oral↗

PubMedDate not supplied

Breast cancer; tumor neovasculature and the effect of tissue inhibitor of metalloproteinases-1 (TIMP-1) on angiogenesis.

Microvessel density has been proposed as a prognostic factor in breast carcinoma. In paired samples of human breast carcinoma and the adjacent non-neoplastic tissue, proliferating microvessels were associated with in situ ductal and lobular carcinomas. In invasive carcinomas, the microvessels were located within the tumor stroma. Recombinant tissue inhibitor of metalloproteinases-1 (rTIMP-1) was produced in a baculovirus system to examine its effect on angiogenesis. When present as a molecule of 29 kDa, rTIMP-1 inhibited matrix metalloproteinase (MMP) activity. However, a 66 kDa aggregate of TIMP-1 did not block MMP activity, although it inhibited in vitro angiogenesis as the 29 kDa form did. Studies have been initiated to characterize the effects of overexpression of TIMP-1 on breast carcinoma cells. Preliminary findings show TIMP-1 mediated changes in morphology and downregulation of MMP activity. These findings suggest that the angiogenesis inhibitory activity of TIMP-1 is unrelated to its antimetalloproteinase activity and that TIMP-1 may affect cellular function in different ways.

Animals↗

PubMedDate not supplied

Bystander effect caused by cytosine deaminase gene and 5-fluorocytosine in vitro is substantially mediated by generated 5-fluorouracil.

Because it appears impossible to transfer toxic genes to all the cells of a cancer, the bystander effect is critical to induce effective antitumor effects. In the present study, possible in vitro mechanisms of the bystander effect by the cytosine deaminase (CD) gene and 5-fluorocytosine (5-FC) were investigated. CD-transduced cancer cells exhibited much higher sensitivity to 5-FC compared to parental cells. CD-transduced cells caused killing of neighboring parental cells in the presence of 5-FC, irrespective of direct cell-to-cell contact. Media conditioned by CD-transduced cells and 5-FC contained considerable amounts of 5-fluorouracil (5-FU) and exhibited profound cytotoxicity on parental cells. Furthermore, this killing ability of conditioned media correlated well with 5-FU levels converted from 5-FC by CD-transduced cells. CD was shown not to be secreted into media from cells. These results indicate that diffusible 5-FU plays the substantially causative role in the in vitro bystander effect caused by the CD/5-FC system.

Animals↗

PubMedDate not supplied

Analysis of intrahepatic invasion of hepatocellular carcinoma using fluorescent dye-labeled cells in mice.

Despite intensive efforts in the treatment of hepatocellular carcinoma (HCC), its prognosis remains poor, mainly because of intrahepatic metastasis. It is, therefore, important to investigate the invasive and metastatic behavior of HCC. To examine this, murine HCC cells were labeled with the fluorescent carbocyanine dye, DiI and implanted under the capsule of the liver of syngeneic mice. Optimal conditions are described for labeling HCC cells with DiI. Histological analysis using fluorescent and confocal microscopes revealed that HCC cells migrate to and invade the adjacent portal vein, but not the adjacent central vein. Conversely, DiI-labeled hepatocytes were shown not to migrate in the liver. These results suggest that intrahepatic metastasis of HCC occurs by invading the portal venous system. Furthermore, it is indicated that orthotopic implantation of fluorescent dye-labeled tumor cells may be a convenient and useful method to investigate the invasive and metastatic behavior of various types of cancer.

Animals↗