Biomedical subjects

J Itakura

Publications and source records attributed to J Itakura.

23 records · Page 2Linked to original sources

PubMed1994

Blockade of liver macrophages by gadolinium chloride reduces lethality in endotoxemic rats--analysis of mechanisms of lethality in endotoxemia.

We investigated the effects of gadolinium chloride (GdCl3.6H2O), which blocks phagocytosis by liver macrophages, on the mortality, blood tumor necrosis factor (TNF) levels, and hepatotoxicity in a lethal endotoxic shock rat model system [10 mg/kg body weight lipopolysaccharide (LPS) intravenously]. With administration of GdCl3, twice at 0.5 or 5 mg/kg, the survival rate 24 h after LPS injection was 56% and 100%, respectively, whereas the level of TNF in blood was not affected. Microscopic investigation of the liver revealed that the focal necrosis of hepatocytes under endotoxemia was completely protected by the administration of GdCl3 at 5 mg/kg. We then investigated the effects of GdCl3 on superoxide (O2-) production by isolated liver macrophages in vitro. The O2- production by liver macrophages isolated from control rats was suppressed by GdCl3 in a dose-dependent manner. GdCl3 also had a cytotoxic effect on these macrophages. The enhanced O2- production by liver macrophages isolated from sublethal endotoxemic (1 mg/kg) rats was suppressed by pretreatment with GdCl3 (5 mg/kg). It was suggested that lethality in endotoxemia cannot be explained only by the degree of increase in blood TNF levels and that the mechanism by which GdCl3 reduces mortality and hepatotoxicity in endotoxemia possibly includes suppression of superoxide production by liver macrophages.

Animals↗

PubMed1994

Glucagon responses in rabbits with obstructive jaundice and a low energy status in the liver.

Glucagon has a choleretic effect and also stimulates energy-consuming reactions, such as gluconeogenesis and ureogenesis in the liver. The effect of glucagon on energy metabolism in the liver was analyzed in rabbits with obstructive jaundice that had severe liver damage, indicated by significantly lower hepatic energy charge levels. The gluconeogenetic responses to glucagon administration, as shown by increases in the plasma glucose levels, were usually observed in normal rabbits, but these responses were completely depressed after glucagon administration in rabbits with obstructive jaundice. The energy charge levels in the latter animals decreased even further after glucagon administration. Even though the energy consumption for gluconeogenesis after glucagon administration was limited in the jaundiced rabbits, it was sufficient to cause a deterioration in the hepatic energy balance. The above findings show that the administration of glucagon increases the amount of energy expended in the liver following a reduction in the hepatic energy charge in rabbits with obstructive jaundice. Therefore, even though glucagon has a choleretic effect, it should be administered carefully to patients with obstructive jaundice, especially in those with severe liver damage, such as in patients with cholangitis.

Adenine Nucleotides↗

PubMed1993

The indications for tumor mass reduction surgery and subsequent multidisciplinary treatments in stage IV hepatocellular carcinoma.

The indications for tumor-mass reduction surgery and subsequent immunotherapy in patients with stage IV hepatocellular carcinoma (HCC) were elucidated in this study. About 42% of the resected specimens from stage IV-A patients (n = 26) contained well-differentiated multicentrically occurring HCC, which was not found in any of the stage IV-B patients (n = 9). The 2-year survival rate after reduction surgery was 49% for the stage IV-A patients and only 13% for the stage IV-B patients, while 6 of the stage IV-A patients who survived for more than 2 years had no vascular invasion or distant organ metastases. Some of the stage IV patients maintained normal peripheral natural killer (NK) activity and were also able to tolerate surgical insults immunologically, provided that appropriate postoperative immunotherapy was given. Thus, stage IV-A HCC has a greater possibility of containing slow-growing intrahepatic tumor clusters, and the removal of any rapidly growing tumors from among these should be undertaken by reduction surgery followed by subsequent multidisciplinary treatment for residual tumor cells, including appropriate immunotherapy.

Carcinoma, Hepatocellular↗

PubMed1988

[Analysis of human mitochondrial DNA in hepatocellular carcinomas].

Based on the following 3 points: 1) tumor proliferation is energy-dependent, 2) mitochondrial energy-production system is dominant for cell growth, and 3) liver mitochondria (mt) possess their own DNA and RNA synthesizing some of their own proteins including respiratory enzymes such as cytochrome oxidases, a possible relationship between mutations of mt-DNA and clinical status of cell proliferation was examined in 10 HCC patients who underwent liver resection. Mt-DNA at the cancerous and the noncancerous portions of 1g resected liver specimens were separated from the nuclear DNA, and then digested with Hinf I endonuclease. DNA filters were made of the digested mt-DNA fragments on the agarose and polyacrylamide gel. The filters were hybridized with a nick-translated 32P-labeled DNA fragments. In two cases, abnormal mt-DNA were detected. In the first case, the tumor was the massive type and grew rapidly invading the bile duct. One restriction fragment of 3.0 Kb of the cancerous and non cancerous portion became larger by 60 bp. In the second case, regarded as metachronous multicentric HCC, the second largest band of the 3.4 Kb fragment of the cancerous portion showed a wider range but not of the noncancerous portion. The former change may indicate polymorphism but the latter indicates an occurrence of the mutation of mt-DNA. Further studies are required, including examinations on the rest of mitochondrial fragments.

Aged↗

PubMedDate not supplied

Increased cyclin D1 in human pancreatic cancer is associated with decreased postoperative survival.

Cyclin D 1 belongs to a family of protein kinases that have been implicated in cell cycle regulation. In the present study we characterized cyclin D1 expression in 6 cultured human pancreatic cancer cell lines and in normal and cancerous human pancreatic tissues. A 4.4-kb cyclin D1 mRNA transcript was present in all cell lines and in all pancreatic tissues. Cyclin D1 mRNA levels were 2.1-fold higher in the pancreatic cancers than in normal pancreatic tissues (p < 0.0002). Cancer patients with lower cyclin D1 levels (n=16) had a median survival of 15.5 months whereas patients with higher levels (n=16) had a median survival of 6.5 months (p < 0.007). These data indicate that cyclin D1 expression may serve as a predictor of postoperative survival in pancreatic cancer patients, and raise the possibility that treatment modalities blocking cyclin D1 activity may have a future role in the therapy of these patients.

Adult↗