PubMed Health⌕ Search

Biomedical subjects

S Arii

Publications and source records attributed to S Arii.

At least 73 records · Page 4Linked to original sources
PubMed1996

Amelioration by Kupffer cell blockade in hepatic damage induced by cold preservation with subsequent plasma-supplemented perfusion.

The effects of Kupffer cell blockade with gadolinium chloride (GdCl3) on hepatic injury in the cold preservation with subsequent perfusion was investigated. The condition of the liver grafts which were cold-preserved in University of Wisconsin solution was evaluated by measuring the uptake rates of indocyanine green and hyaluronic acid (IUR and HUR), two indices of liver damage. Perfusion injuries after cold storage occurred in 24-hr-preserved liver and progressed further in 36-hr-preserved liver. GdCl3 prevented the decrease in IUR and ameliorated perfusion injuries in the 36-hr-preserved liver, although GdCl3 did not inhibit the decrease in HUR. The HURs were remarkably decreased in the livers stored even for 6 hr, for which the cold-preserved livers were quite viable, whereas IURs were significantly decreased in livers stored for 24 hr or more when perfusion injury was apparently developed. These results suggest that the IUR is an indicator of hepatic perfusion injury in preserved livers and that Kupffer cell blockade may be a promising strategy for the prevention of hepatic injury after cold preservation with subsequent perfusion.

Animals↗
PubMed1996

The preventive effects of OK432 on endotoxin-induced liver injury: liver protection by the modulation of hepatic macrophage function.

The present study was conducted to clarify whether endotoxin-induced liver injury could be improved by modulating the function of hepatic macrophages using OK432, an immunostimulant derived from Streptococcus. OK432 elevated the capacity of hepatic macrophages to produce superoxide and tumor necrosis factor (TNF), and enhanced the mRNA expression of interleukin-1-alpha, -beta, and TNF-alpha in liver nonparenchymal cells (NPC). However, intravenous (iv) preadministration of OK432 reduced the mRNA expression of TNF-alpha in liver NPC enhanced by the endotoxin injection, decreased the serum level of GOT and lactic dehydrogenase (LDH), and improved the survival rate of endotoxin-injected rats. Histological examination revealed a significant reduction in cell vacuolization and focal necrosis in the livers of the endotoxin-injected rats pretreated with OK432. These results indicate that hepatic macrophages play a crucial role in endotoxin-induced liver injury, and that TNF-alpha is one of the factors most likely to be implicated in the development of endotoxin-induced liver injury. Thus, it is suggested that the administration of OK432 provides liver protection by modulating the responsiveness of hepatic macrophages against endotoxin.

Animals↗
PubMed1996

Effects of cholecystokinin and carbachol on membrane fluidity in pancreatic acini.

The effects of pancreatic secretagogues on the membrane fluidity of pancreatic acini were investigated using 1-[4-(trimethylammonium)phenyl]-6-phenyl-1,3,5-hexatriene iodide as a probe. Two kinds of pancreatic secretagogues, one category of which induces acute pancreatitis (cholecystokinin and carbachol) and another which does not induce acute pancreatitis (bombesin, CCK-JMV-180, and secretin), as well as lecithin were used to investigate the effect of changes in membrane fluidity of acini. Our study revealed that the membrane fluidity of the pancreatic acini was unaffected by a physiological dose (10(-11) M) of cholecystokinin. However, stimulation with a supramaximal dose of cholecystokinin (10(-8) M) increased membrane fluidity markedly within 20 min. Membrane fluidity increased dose-dependently with increasing CCK stimulation. A supramaximal dose of cholecystokinin also induced bleb formation and increased LDH release. These phenomena were blocked by simultaneous incubation with CR1505 (Loxiglumide), a potent antagonist of peripheral cholecystokinin receptors. A supramaximal dose of carbachol (10(-3) M) also induced increases in the membrane fluidity. Pancreatic secretagogues that do not induce acute pancreatitis did not induce alterations in membrane fluidity. Lecithin increased both membrane fluidity and LDH release. These observations suggest that this increase in membrane fluidity of the pancreatic acini may be related to membrane alteration and to functional damage of the acini. These observations [correction of observation] can serve as a window to detect the development of acute pancreatitis at an early stage.

Animals↗
PubMed1996

HLA-DR antigen and interleukin-2 receptor expression on primary-cultured human hepatic macrophages in relation to liver cirrhosis and hepatitis virus infection.

We analyzed primary-cultured human hepatic macrophages (HHMphi) from 12 patients with non-cirrhotic and cirrhotic livers for cell surface expression of HLA-DR antigen and interleukin-2 receptor (IL-2R). Compared to the relatively abundant HLA-DR antigen, IL-2R expression was generally low. No significant difference was observed between HLA-DR antigen expression nor IL-2 receptor expression. HHMphi from patients with serum hepatitis viral markers, however, expressed significantly more HLA-DR antigen than did HHMphi of patients without viral markers, which suggest a possible role of HHMphi as antigen-presenting cells (APC) in viral hepatitis. This direct, quantitative measurement of cell surface molecule expression on hepatic macrophages of human may provide an important clue to the pathophysiology of human liver disorders.

Aged↗
PubMed1996

Clinical significance of vascular endothelial growth factor and basic fibroblast growth factor gene expression in liver tumor.

Hepatocellular carcinoma (HCC) is a typical hypervascular tumor. However, the relationship between the vascularity of HCC and the expression of angiogenic factors has not been investigated. In addition, no detailed studies have examined the possible involvement of angiogenic factors in the grade of malignancy of HCC. The aim of this study was to determine which angiogenic factors regulate tumor angiogenesis and contribute to the invasive ability of liver tumors, especially of HCC. Northern blot analysis was used to examine the transcriptional expression of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (FGF), and acidic FGF in resected surgical specimens (20 HCC and 9 metastatic liver tumors). Correlations between messenger RNA (mRNA) expression and arteriographic findings, as well as histopathological findings, were evaluated. Immunohistochemistry was performed to identify the localization of cells expressing VEGF in HCC. Higher levels of VEGF mRNA were observed in 12 of 20 HCC and 2 of 9 metastatic liver tumors than in corresponding nontumorous tissues. The degree of VEGF mRNA expression was significantly correlated with the intensity of tumor staining in angiograms (P<.01). On immunohistochemical observation, VEGF protein was intensely detected in HCC cells. Furthermore, basic FGF mRNA was detected in 9 of 20 HCC and was related to the capsular infiltration of cancer cells (P<.05). In contrast, no significant difference was observed in the very low levels of acidic FGF mRNA found in the tumorous and nontumorous portions of the liver. In conclusion, these results suggest that VEGF contributes to angiogenesis of liver tumors, whereas basic FGF may be involved in the invasion of HCC into the surrounding tissues.

Aged↗
PubMed1996

Chemical mediators released by primary-cultured human hepatic macrophages in patients with and without cirrhosis: a study in tumor-bearing patients.

To elucidate the possible role of chemical mediators in modulating the host-defense activity of patients with cirrhosis, primary-cultured human hepatic macrophages (HHMphi) were obtained from cirrhotic and noncirrhotic patients who received liver resections because of the presence of malignant liver tumors. The cirrhotic and noncirrhotic groups consisted of patients with similar malignancies: noncirrhotic patients had normal liver function and normal liver histology for nontumorous portions. The cultured HHMphi were analyzed for their ability to release chemical mediators with specific activities in the host defense system. Dose-dependent increases in superoxide release, interleukin-1 (IL-1) release, and, within a relatively narrow range, prostaglandin-E2 (PGE2) release were observed in opsonized zymosan (oz)-stimulated HHMphi derived from both cirrhotic and noncirrhotic patients. The release of O2- and PGE2 from HHMphi derived from cirrhotic patients was significantly less than HHMphi derived from noncirrhotic patients, whereas the release of IL-1 was significantly greater. Although, because of the limited sample availability, only tumor-bearing patients were studied, the mediator-releasing ability of HHMphi derived from cirrhotic patients was significantly different from the ability of HHMphi derived from noncirrhotic patients with similar malignancies. This phenomenon may be related to altered host defenses in patients with cirrhosis.

Adjuvants, Immunologic↗
PubMed1996

Overexpression of matrix metalloproteinase 9 gene in hepatocellular carcinoma with invasive potential.

The prognosis for hepatocellular carcinoma (HCC) depends mainly on the clinicopathological characteristic regarding invasion and metastasis. In addition, another distinguishing feature of HCC is the high incidence of concomitant liver cirrhosis, in which the extracellular matrix proliferates markedly. Therefore, the present study was designed to investigate the molecules responsible for the invasion potential of HCC by focusing on matrix metalloproteinase (MMP) in particular, MMP-2 and MMP-9 and the corresponding tissue inhibitor of metalloproteinase (TIMP-2 and TIMP-1), because these enzymes participate in the degradation of the extracellular matrix including the basement membrane. Tumorous and adjacent nontumorous liver samples were obtained from 23 HCC patients who underwent a partial hepatectomy. In 16 of the 23 HCC samples, transcripts for MMP-9 were detected in the tumorous tissues, and 15 of 16 of these samples showed stronger expression in the tumorous tissues than in the nontumorous tissues. On the other hand, MMP-2 messenger RNA (mRNA) was detected in 18 of the 23 cases. Eight of these 18 cases showed more intense expression in the tumorous tissues than in the nontumorous tissues, whereas the expression levels were lower in the tumorous tissues than in the nontumorous tissues in 7 of 18 samples. With respect to the correlation between the clinicopathological features and mRNAs expression, it was found that the expression of MMP-9 mRNA in HCC with capsular infiltration was significantly higher than in HCC without capsular infiltration. HCC with capsular infiltration also tended to have a higher ratio of MMP-9 mRNA expression to TIMP-1 mRNA expression. In addition, the expression of MMP-2 mRNA in nontumorous cirrhotic tissues was significantly higher than in nontumorous tissues from patients with chronic hepatitis. Immunohistochemical examinations revealed that MMP-9 immunoreactivity was the most intense in the HCC cells, particularly in those cells in the marginal areas of the tumorous tissues. In conclusion, the present study shows that MMP-9 is closely participated in capsular infiltration in HCC.

Adult↗
PubMed1996

kan-1 (bile acid CoA:amino acid N-acyltransferase) messenger RNA as a novel predictive indicator for prognosis of hepatocellular carcinoma patients after partial hepatectomy.

We identified kan-1 complementary DNA (cDNA), the sequence of which is identical to bile acid CoA:amino acid N-acyltransferase (BAT), a liver enzyme that catalyzes the conjugation of bile acids with glycine or taurine. Kan-1(BAT) messenger RNA (mRNA) levels of the resected specimens obtained from 37 hepatocellular carcinoma (HCC) patients were studied in an attempt to evaluate prognostic significance in HCC patients after partial hepatectomy. Using Northern blot hybridization, kan-1(BAT) mRNA levels were quantified in tumorous and nontumorous tissues, and the ratio of the former to the latter was defined as the kan-1(BAT) ratio. Twelve patients had a kan-1(BAT) ratio < 0.5 (low kan-1[BAT] ratio), and 25 patients had a ratio >0.5 (high kan-1[BAT] ratio). The patients with a low kan-1(BAT) ratio demonstrated poorer survival than the patients with a high kan-1(BAT) ratio (P = .0013). The overall estimated hazard ratio for death in patients with a low kan-1(BAT) ratio was 68.05 according to a multivariate model (P = .0005). Thus, the kan-1(BAT) ratio may serve as a new molecular prognostic marker in HCC patients, following hepatic resection.

Acyltransferases↗
PubMed1996

A prospective randomized trial of the preventive effect of pre-operative transcatheter arterial embolization against recurrence of hepatocellular carcinoma.

To clarify whether pre-operative transcatheter arterial embolization (TAE) improves survival after hepatectomy, a prospective randomized comparative study was done. Of a total of 115 registered patients having solitary hepatocellular carcinoma (HCC) 2 to 5 cm in diameter, 18 (15.7%) were excluded after randomization. As a result, 97 patients were chosen as subjects and divided into two groups: hepatectomy with (group A: n=50) and without (group B: n=47) pre-operative TAE. The period of observation of the patients who survived the surgery was between 4.0 and 6.6 years. The randomization appeared to have provided well-balanced groups of patients and the clinico-pathological characteristics of the two groups were quite similar. The necrotic part of the cancerous lesions, as confirmed by operative specimens, amounted to 74.8+/-33.4% (mean +/-SD) in group A and 6.8+/-7.2% in group B (P<0.01). However, the cancer-free survival rates after hepatectomy in both groups showed little difference (39.1+/-7.0 (%+/-SE) and 31.1+/-0.1, respectively). We speculate that TAE is not effective against such HCC accessory lesions as minute intrahepatic metastasis and tumor thrombus and that pre-operative TAE does not improve post-operative survival.

Adult↗
PubMed1995

Reduced expression of kan-1 (encoding putative bile acid-CoA-amino acid N-acyltransferase) mRNA in livers of rats after partial hepatectomy and during sepsis.

We isolated a cDNA clone, kan-1, from a rat liver cDNA library using a reverse transcriptase PCR cloning method. The kan-1 cDNA encoded a polypeptide of 420 amino acids, and was 70 and 69% identical in nucleotide and amino acid sequences respectively with human liver bile acid-CoA-amino acid N-acyltransferase (BAT). Thus Kan-1 is probably a rat homologue of human BAT (rBAT). Kan-1/rBAT mRNA was mainly expressed in the livers of adult rats and rats immediately after, but not before, birth. It was expressed in the hepatocytes, the sinusoidal endothelial cells and the Kupffer cells of the liver. An anti-Kan-1/rBAT polyclonal antibody detected a protein of molecular mass 46 kDa in the liver. After partial hepatectomy, the levels of Kan-1/rBAT mRNA decreased at 6 and 12 h in the regenerating liver. In a sepsis model, hepatic expression of Kan-1/rBAT mRNA decreased at 6 and 12 h after caecal ligation and puncture. The kinetics of Kan-1/rBAT mRNA expression suggests that it may play a role in acute-phase reactions.

Acyltransferases↗
PubMed1995

Involvement of thromboxane A2-thromboxane A2 receptor system of the hepatic sinusoid in pathogenesis of cold preservation/reperfusion injury in the rat liver graft.

This study was designed to investigate the possible involvement of the thromboxane A2 (TXA2)-TXA2 receptor (TXA2R) system of the hepatic sinusoid in cold preservation/reperfusion injury in liver grafts. Rat livers were preserved in cold University of Wisconsin solution for either 6 or 24 hr. The number of TXA2Rs in sinusoidal endothelial cells isolated from 0-, 6-, and 24-hr preserved liver specimens was 22.50 +/- 1.80 x 10(3)/cell, 12.66 +/- 1.00 x 10(3)/cell, and 4.17 +/- 0.65 x 10(3)/cell, respectively. Kd and Bmax at 0 hr, 6 hr, and 24 hr of preservation were 8.54 +/- 1.26 nM and 37.34 +/- 3.01 fmol/10(6) cells, 7.08 +/- 1.14 nM and 12.66 +/- 1.00 fmol/10(6) cells, and 1.91 +/- 0.10 nM and 3.88 +/- 0.59 fmol/10(6) cells, respectively. The administration of OKY-046 (inhibitor of TXA2 synthesis) to the University of Wisconsin solution suppressed this reduction in TXA2R number. Furthermore, the concentration of TXA2 in hepatic sinusoid was decreased by OKY-046. In a reperfusion experiment, liver tissue preserved for 24 hr exhibited a higher reperfusion pressure, and effluent levels of both aspartate aminotransferase and lactate dehydrogenase were markedly elevated. The addition of OKY-046 to the preservation solution, however, prevented the rise in reperfusion pressure almost completely and the increase in effluent enzyme levels. This study showed that the TXA2Rs in sinusoidal endothelial cells were internalized through binding with TXA2 during cold preservation, causing activation of the TXA2-TXA2R system. This activation apparently induces an increase in reperfusion pressure, possibly due to sinusoidal contraction, resulting in microcirculatory disturbances.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Enhanced expression of multiple protein tyrosine phosphatases in the regenerating mouse liver: isolation of PTP-RL10, a novel cytoplasmic-type phosphatase with sequence homology to cytoskeletal protein 4.1.

To elucidate the role that protein tyrosine phosphatase (PTPs) may play in liver regeneration, PTPs expressed in the mouse liver after partial hepatectomy (PH) were investigated by a PCR-based cloning method. Sequencing of 115 cDNA clones identified 10 different sequences including MPTP (T cell PTP), PTP-1B, PTP-P19, mR-PTP mu, R-PTP alpha, PTP NE-3 (PTP-P1), R-PTP-kappa and the murine homologue of human LAR. The remaining two sequences, PTP-RL9 and PTP-RL10, encoded novel PTPs. PTP-RL10 cDNA contained an open reading frame of 1176 amino acids with no apparent membrane-spanning region. The amino-terminal region had sequence homology to those of human erythrocyte protein 4.1 and ezrin, cytoskeletal proteins. In the regenerating liver, the levels of five PTP gene mRNAs (MPTP, PTP-P19, R-PTP alpha, LAR homologue, and PTP-RL9) increased within 6 h, decreased to the normal level by 24 h, and increased again at 48 to 72 h after PH. The levels of PTP-1B and R-PTP-kappa mRNAs peaked within 6 h, decreased gradually, and returned to the normal level by 168 h after PH. In contrast, the levels of two PTP mRNAs (mR-PTP mu and PTP-RL10) peaked at 48 to 72 h, and returned to the normal level by 168 h after PH. No expression of PTP NE-3 was detected in the liver by Northern blotting. The differential expression of multiple PTPs during the pre-replicative and post-replicative stages of liver regeneration suggests that PTPs are involved in the regulation of growth and differentiation of liver cells.

Amino Acid Sequence↗
PubMed1995

Expression of cytokine genes during liver regeneration after partial hepatectomy in rats.

In the present study to demonstrate the relationship between cytokines and liver regeneration we investigated by Northern blot hybridization the cytokine gene induction in the regenerating liver and several other organs (spleen, lung, and kidney) in the rat after partial hepatectomy (PH). We also examined whether Kupffer cells and the spleen are involved in the induction of cytokine mRNA in the regenerating liver. Both IL-1 alpha and beta mRNA increased transiently 1/2 to 1 hr after PH in nonparenchymal cells (NPC) of the regenerating liver; they reached a maximum before the peak of hepatocyte DNA synthesis. PH also induced a slight, but significant, gene expression of IL-1 in lung and kidney in the early postoperative period. TNF-alpha mRNA increased gradually in the spleen, but not the liver, of partially hepatectomized rats at 3 to 12 hr and then reached a peak at 24 hr after PH. IL-6 transcripts were not detected in the regenerating liver, spleen, lung, or kidney during liver regeneration. In contrast, no cytokine gene expression was induced in any of these four organs during the first 3 days after sham operation or unilateral nephrectomy. When Kupffer cell activity was suppressed by gadolinium chloride pretreatment, or when splenectomy was performed 24 hr before PH, the constitutive IL-1 alpha and beta mRNA expressions in NPC of the normal rat liver were completely suppressed. In conclusion, the present study demonstrates, for the first time, the specific kinetics of cytokine gene expression in the liver, spleen, lung, and kidney after PH.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Participation of hepatic macrophages and plasma factors in endotoxin-induced liver injury.

The present study was designed to investigate the mechanism responsible for endotoxin-induced liver injury, based on the working hypothesis that hepatic macrophages activated by endotoxin play a key role in the development of this injury. At both the protein and the transcription levels, the intravenous administration of endotoxin was shown to have increased the capacity of hepatic macrophages to produce chemical mediators. To inhibit the function of hepatic macrophages, gadolinium chloride (GdCl3), a specific inhibitor of resident hepatic macrophages, was preadministered to rats before endotoxin injection. GdCl3 reduced the elevated glutamic oxaloacetic transamiase and lactate dehydrogenase serum levels produced by endotoxin treatment, suppressed the increased mRNA expression of tumor necrosis factor (TNF-alpha) produced in liver nonparenchymal cells by endotoxin, and then improved the survival rate of lipopolysaccharide-injected rats. These results indicated that hepatic macrophages played a crucial role in liver injury and that TNF-alpha was the most likely factor implicated in the development of endotoxin-induced liver injury. Furthermore, we found that liver injury did not progress during perfusion of endotoxin-pretreated extirpated liver with lactate Ringer's solution, whereas liver perfused with plasma developed remarkable hepatic impairment, which was inhibited almost completely by GdCl3-pretreatment; moreover, addition of heparin to the perfusate also prevented this deterioration. Thus, the present study showed that the activation of hepatic macrophages and factors in the plasma were two essential elements in the occurrence and development of endotoxin-induced liver injury.

Animals↗
PubMed1995

Liver transplantation and hepatic sinusoidal cells.

Primary graft non-function of the liver is one of the common causes of retransplantation. Although the mechanism of primary graft non-function is not fully understood, a potent elucidative pathogenesis is microcirculatory disturbance due to sinusoidal damage during cold preservation and reperfusion. In this article, we discuss the possible participation of sinusoidal endothelial cells and Kupffer cells (KC) in the cold preservation/reperfusion injury. Kupffer cell activation and endothelial damage were developed during the cold preservation with subsequent reperfusion. Activated KC produced a large quantity of tumour necrosis factor (TNF)alpha, and then increased ICAM-1 expression in sinusoidal endothelial cells. The reperfusion experiment showed that hypercoagulability and leucocyte adherence in the liver are strongly involved in reperfusion injury, and that KC blockade as well as anti-TNF alpha antibody and anti-ICAM-1 antibody ameliorate the injury in association with a reduction of both fibrin deposition and leucocyte accumulation. Ultrastructural observation also revealed the beneficial effect of KC blockade on the maintenance of sinusoidal endothelial cells. Furthermore, the thromboxane A2-thromboxane A2 receptor system in the sinusoid was also found to participate in this pathogenesis. Thus, these results suggested that cold preservation/reperfusion injury is due to sinusoidal microcirculatory disturbance, which is, at least in part, induced by communication between activated KC and sinusoidal endothelial cells through, among others, ICAM-1, cytokines and prostanoids.

Cold Temperature↗