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Hiroko Iijima

Publications and source records attributed to Hiroko Iijima.

17 recordsLinked to original sources
PubMed2007

Phagocytosis of ultrasound contrast agent microbubbles by Kupffer cells.

Delayed parenchymal phase images of the liver more than 5 min after IV injection of ultrasound contrast agents are thought to be related to the phagocytosis of contrast agent microbubbles by macrophages. In this study, we examined whether liver-specific macrophages, Kupffer cells, phagocytosed the microbubbles and whether their elimination affected the delayed parenchymal images of the liver. Phase-contrast microscope observations showed that Kupffer cells phagocytosed various contrast agents in vitro. Among the contrast agents used, 99% of Sonazoid and Optison, and 47% of Levovist were phagocytosed, whereas only 7.3% of SonoVue and 0% of Imavist were phagocytosed. Elimination of Kupffer cells in vivo by gadolinium chloride (GdCl(3)) resulted in decreased intensity of the delayed parenchymal images with Sonazoid and Levovist, while SonoVue showed no changes compared with control. Our findings suggested that Kupffer cells phagocytosed contrast agents and they were responsible for the delayed images of contrast ultrasound in the liver.

Albumins↗
PubMed2006

Ultrasound contrast agent, Levovist microbubbles are phagocytosed by Kupffer cells-In vitro and in vivo studies.

Phase contrast microscopy showed that Levovist microbubbles were phagocytosed by cultured Kupffer cells and moved gradually toward the nucleus from the cell surface. They were diminished in size and disappeared within 30min by diffusion of the gas contained within the microbubbles. In an in vivo study, confocal laser scanning microscopy demonstrated that Levovist microbubbles were trapped and phagocytosed by Kupffer cells. No microbubbles were observed attached to the sinusoidal endothelium. Our findings suggest that liver-specific images obtained following intravenous injection of Levovist are composed of signals from microbubbles phagocytosed by Kupffer cells.

Journal Article↗
PubMed2006

Quantification of hepatic parenchymal blood flow by contrast ultrasonography with flash-replenishment imaging.

Flash-replenishment (FR) utilizes destruction of microbubbles in the scan volume by high-power ultrasound and enables to observe reperfusion at a low acoustic power. In this paper, we introduced theoretic equation between probability density function (PDF) of the transit time in the scan volume and time intensity curve (TIC) measured by FR method. From the equations, it was explained that the mean transit time (MTT) through the scan volume was calculated from the plateau level and tangent of the initial slope. Animal experiments were also performed to measure TIC in the parenchymal region of the liver using FR method. From the result of the TIC, the variant of the PDF for the transit time was found to be small and the average MTT was 11.1 s. Hepatic blood flow by an ultrasonic transit time flowmeter was also measured in the same experiment, and adequate correlation was obtained from between the two methods. The results suggested that the FR method, which is a noninvasive measurement, can predict the blood flow of the liver.

Animals↗
PubMed2005

Isolation and characterization of a novel immunomodulatory alpha-glucan-protein complex from the mycelium of Tricholoma matsutake in basidiomycetes.

Tricholoma matsutake, a high-class edible mushroom in Japan, has been reported to have excellent biological activities, but difficulty in cultivating the fruit bodies and limited bulk availability have restricted detailed studies. We have developed a method of culturing in tanks, enabling the bulk supply of the mycelia. The preparation (CM6271) exerts modulative effects on the immune competence of mice and rats. In this study, a sodium hydroxide extract of CM6271 was defatted followed by fractionation with a combination of ion exchange chromatography and gel filtration in order to identify the components involved in the expression of the activity, and a single peak fraction (MPG-1) was obtained with reversed phase chromatography. MPG-1 was a glycoprotein (sugar:protein ratio, 94.3:5.7) with a relative molecular mass of 360 kDa, and the sugar moiety contained about 90% glucose. NMR spectra and methylation analysis revealed that the alpha-1,4-linkage was the predominant glucan linkage with alpha-1,6- and alpha-1,2-linkages in the minority. The amino acid composition in the protein moiety was rich in glutamine, alanine, asparagine, leucine, glycine, valine, serine, threonine, isoleucine, and proline. MPG-1 was resistant to degradation with amylase or protease. The oral administration of MPG-1 promoted, in a dose-dependent manner, the recovery of the mouse natural killer cell activity and serum IL-12 level that had been reduced by the loading of restraint stress. The dose of MPG-1 (25 mg/kg) required for the expression of the effect decreases to 1/12 of that of CM6271 (300 mg/kg). Furthermore, MPG-1 formed a complex with TGF-beta1 in vitro, modulating the biological activity of TGF-beta1 by binding to its active form. These results indicate that the mycelium of T. matsutake contains a novel alpha-glucan-protein complex with immunomodulatory activities.

Animals↗
PubMed2005

Diagnosis of NASH using delayed parenchymal imaging of contrast ultrasound.

BACKGROUND AND AIMS: Non alcoholic steatohepatitis (NASH) is one of the representative liver diseases in the developed countries. Diagnosis of NASH is dependent on histological findings from liver biopsy. Usefulness of contrast ultrasound with Levovist for diagnosis of NASH is described. METHODS AND MATERIALS: Clinical study: Ultrasound contrast agent, Levovist of 2.5g was injected intravenously. The liver was scanned at 5, 10, 15, 20, 30, 40, and 50min after Levovist injection in different planes using a contrast specific ultrasound mode. Changes in microbubble accumulation in the liver were evaluated. The signal intensity from regions of interest (ROI) on the contrast images was measured and accumulation and decrescence of microbubbles were estimated using the time intensity curves (TICs). The image data and TICs were evaluated by blind reviewers. Fifteen patients with NASH, 8 with alcoholic steatohepatitis (ASH), 45 with non alcoholic fatty liver (NAFL), 10 with chronic hepatitis C (CHC) and 10 healthy volunteers were studied. Animal study: Methionine-choline-deficient diet (MCDD) fed rats were used for NASH model. Correlation between microbubble accumulation and morphological and functional changes of sinusoidal endothelium and macrophage was evaluated. RESULTS: The maximum intensity of contrast ultrasound was decreased and time course decrescence was more rapid in NASH than the other groups. These changes were correlated to the degree of centrilobular and pericellular fibrosis but not to steatosis in histological study. Disturbance of microbubble accumulation was correlated with sinusoidal function rather than morphological changes such as fibrosis and parenchymatitis in the animal studies. CONCLUSIONS: The Levovist contrast study enables differential diagnosis between NASH and other diseases that provoke steatosis and fibrosis.

Journal Article↗
PubMed2005

Differential diagnosis of pancreatic tumors using ultrasound contrast imaging.

BACKGROUND: The development of equipment and contrast agents for ultrasound imaging has contributed to major breakthroughs in the diagnosis of pancreatic tumors. We aimed to determine the diagnostic effectiveness of contrast ultrasound with Levovist, using the Agent Detection Imaging (ADI) technique, in 50 patients with pancreatic tumors. METHODS: We studied 50 cases of histologically proven pancreatic disease; 39 carcinomas, 2 endocrine tumors, 4 intraductal papillary mucinous carcinomas (IPMCs), and 5 cases of tumor-forming pancreatitis (TFP). Vascular and perfusion images of contrast-enhanced ultrasound (CE-US) were used for the evaluation of tumor vascularity and parenchymal perfusion of the tumor, respectively. The hemodynamics of the tumor, and the diagnostic capacity of CE-US were compared with those shown by computed tomography (CT). The histological diagnosis in all cases was made from either biopsy or surgical specimens. RESULTS: Thirty-four cases of pancreatic carcinoma (87%) showed a hypovascular and hypoperfusion pattern. The endocrine tumors showed a heterogeneous hypervascular and hyperperfusion pattern. All IPMC cases showed hypervascularity of the nodules inside the tumors. TFP showed an isovascular and homogeneous isoperfusion pattern. When tumors showing a hypovascular or hypoperfusion pattern on CE-US were diagnosed as carcinomas, 34 of the 39 carcinomas (87%) fit this criterion, with a 95% confidence interval (CI) of 73%-96%, whereas, on CT, 31 of the 39 were diagnosed as carcinoma; (sensitivity, 79%). The sensitivity and accuracy of CT were inferior to those of CE-US. Results of comparison between the CE-US findings and the histological diagnosis were as follows. The one papillary adenocarcinoma showed a hypervascular and hyperperfusion pattern; the 32 well or moderately differentiated adenocarcinomas showed a hypovascular and hypoperfusion pattern; and in the poorly differentiated adenocarcinomas, 2 cases of scirrhous type showed a hypovascular and hypoperfusion pattern, and the 4 cases of medullary type showed an isovascular and isoperfusion pattern. CONCLUSIONS: The differences in vascularity of pancreatic carcinomas depicted by CE-US were associated well with differences in histology. CE-US, by the ADI technique, is useful for the diagnosis of pancreatic tumors.

Adenocarcinoma, Papillary↗
PubMed2004

Differential diagnosis of hepatic nodules using delayed parenchymal phase imaging of levovist contrast ultrasound: comparative study with SPIO-MRI.

T2-weighted fast spin echo images and T2*-weighted gradient-echo images of superparamagnetic iron oxide magnetic resonance imaging (SPIO-MRI) have been reported to reflect the number and function of macrophages in reticuloendothelial organs and be useful to differentiate malignant tumors from benign nodules of liver. We tried to prove that contrast-enhanced ultrasound can diagnose hepatocellular carcinoma (HCC) by comparing the findings of SPIO-MRI and the findings of the liver parenchyma on the delayed parenchymal phase of ultrasound imaging using the intravenous contrast agent Levovist, not through the evaluation of vascular imaging. Forty-six patients (52 nodules) with histopathological diagnosis of hepatic tumors were studied. They consisted of 11 non-malignant nodules (six regenerative nodules and five dysplastic nodules) and 41 HCC. All the patients were examined by Levovist contrast-enhanced ultrasonography and SPIO-MRI. The delayed liver parenchymal images of contrast-enhanced ultrasound using the intravenous contrast agent Levovist were similar to those observed on SPIO-MRI. The similarity of both findings suggests that delayed phase imaging by Levovist is closely related to the number and function of Kupffer cells in liver tumors. The diagnostic accuracy of contrast-enhanced ultrasound for HCC was high (90.4%) demonstrating that it is as reliable as SPIO-MRI.

Journal Article↗
PubMed2004

Usefulness of contrast-enhanced ultrasonography with a new contrast mode, Agent Detection Imaging, in evaluating therapeutic response in hepatocellular carcinoma treated with radio-frequency ablation therapy.

Objective: The therapeutic response of radio-frequency ablation (RFA) for hepatocellular carcinoma (HCC) was evaluated by contrast-enhanced ultrasonography (US) using a new contrast mode, agent detection imaging (ADI), and its usefulness was compared with that of dynamic computed tomography (CT). Materials and methods: Forty patients with 64 nodules diagnosed as HCC histologically and/or by various imaging modalities were evaluated with ADI (1 and 7 days after treatment) and Dynamic CT (7 days after treatment). Results: ADI and dynamic CT revealed residual lesions in 15 and 12 nodules, and no residual lesions in 45 and 52 nodules, respectively. ADI yielded indeterminate findings in four nodules; although the vascular phase showed minute residual tumor vessels, the tumor appeared to be completely contained within the ablated area in the delayed phase. In these indeterminate cases, US-guided biopsies of the areas of residual vascularity revealed no viable cancer cells; only degenerated tissues. Conclusion: In assessing the therapeutic response of RFA for HCC, ADI has a similar competence to dynamic CT. Even if the vascular phase of contrast-enhanced US shows minute residual vessels, as long as the tumor is safely contained within the ablated area in the delayed phase, the cancer cells are likely to be degenerated.

Journal Article↗
PubMed2004

Inhibition of decrease in natural killer cell activity in repeatedly restraint-stressed mice by a biological response modifier derived from cultured mycelia of the basidiomycete Tricholoma matsutake.

OBJECTIVE: To develop a method to cope with stress-induced reduction in immunocompetence, we evaluated the immunomodulatory activities of a biological response modifier derived from the mycelia of the basidiomycete Tricholoma matsutake (CM6271) in mice under repeated restraint stress. METHODS: C57BL/6 mice were inserted, one per tube, into 50-ml polypropylene tubes into which more than 30 ventilation holes had been drilled, and were restrained everyday for 20 days in this fashion for set periods of time. Natural killer (NK) cell activity and NK1.1-positive cell counts in the spleen, ACTH and corticosterone levels in the blood were determined. CM6271 was orally administered daily during the restraint stress period. RESULTS: (1) When the mice were restrained in a confined space for 6 h per day for 20 days, the NK cell activity and the NK1.1-positive cell counts in the spleen significantly decreased after day 5 with an increase in the blood ACTH and corticosterone levels. (2) Oral administration of CM6271 during the restraint stress period significantly prevented the stress-induced decrease in NK cell activity. The effect was dependent on the timing, duration, and doses administered. (3) CM6271 did not significantly affect the splenic NK1.1-positive cell counts or the levels of blood ACTH and corticosterone in restraint-stressed mice. CONCLUSION: The above findings suggest that CM6271 inhibits the restraint stress-induced decrease of NK cell activity in a timing of administration and dose-dependent manner.

Animals↗
PubMed2003

Expression of matrix metalloproteinase, tissue inhibitors of metalloproteinase and adhesion molecules in silicotic mice with lung tumor metastasis.

The number of metastatic foci in silicotic mice is approximately 1.5-fold that in normal mice and in mice treated with TiO2 as inert particles. Expression of matrix metalloproteinases (MMPs) tissue inhibitors of metalloproteinases (TIMPs) and selectins was investigated in silicotic mice with lung tumor metastasis. Expression of MMP-9 and P-selectin mRNA, but not MMP-2 and E-selectin, increased significantly, showing decreases of the ratio of expression in TIMPs/MMP-9 in tumor-bearing silicotic mice compared with the tumor-bearing normal mice and mice treated with TiO2. Pretreatment with anti-P-selectin antibody inhibited number of metastatic foci significantly in silicotic mice, while pretreatment of animals with anti MMP-9 antibody showed slight decrease of metastatic foci. This evidence indicated that up-regulation of P-selectin expression contributed to enhanced rate of tumor metastasis in lung with silicosis.

Animals↗
PubMed2003

Enhanced recovery of NK cell activity in mice under restraint stress by the administration of a biological response modifier derived from the mycelia of the basidiomycete Tricholoma matsutake.

Some types of stressor act on the immune system via the network comprising the endocrine-immune-nervous systems, and are reportedly responsible for the onset of diseases as well as giving impetus to their advance. It is important for the maintenance and promotion of health to cope with stress-induced changes in immunocompetence. Therefore, we studied the effects of administration of a novel biological response modifier (CM6271) derived from the mycelia of the basidiomycete Tricholoma matsutake on the NK cell activity in mice under restraint stress, in order to evaluate its potential to modulate immune responsiveness in stress-loaded individuals. (1) When C57BL/6 mice were restrained in 50-ml tubes for more than 6 h, splenic NK cell activity decreased significantly, but recovered gradually after the mice were released. The extent of the reduction of activity and the degree of recovery depended on the duration of the restraint. (2) The oral administration of CM6271 caused a significant acceleration of the recovery of the activity. This effect was dependent on the timing of administration and the dose given. (3) The administration of CM6271 had no clear effect on the blood levels of ACTH, corticosterone or lipid peroxide levels in the liver. These findings suggest that CM6271 promotes recovery from the decrease in NK cell activity induced by restraint stress.

Adrenocorticotropic Hormone↗
PubMed2003

[Effect of PSK on Th1/Th2 balance in tumor-bearing mice].

We investigated the effect of PSK on Th1/Th2 balance in tumor-bearing mice. PSK was intraperitoneally administered to Meth A-bearing BALB/c mice, and PSK caused regression of the Meth A tumor. The results of Winn assay suggested that the effect of PSK was dependent on CD4+T cells. Furthermore, spleen cells were cultured with mitomycin C-treated Meth A, after which the cytokine concentration was measured by ELISA. IFN-gamma production was increased and IL-4 showed almost no change in PSK-administered mice. In another experiment, PSK was orally administered to colon 26-bearing mice in which tumors were inoculated into the subserosal space of the cecum. Mesenteric lymph nodes cells were cultured with mitomycin C-treated colon 26 cells. IFN-gamma production was increased, but not so much as to be statistically significant, and IL-4 was significantly decreased in PSK-administered mice. PSK increased IFN-gamma and IL-12 p70 production and decreased IL-4 production when spleen cells were stimulated with Con A together with PSK in vitro. As suggested from these results, PSK might induce cytokine production that works for Th1 differentiation, and suppress cytokine production that works for Th2 differentiation, and shift the Th1/Th2 balance toward Th1 dominance in tumor-bearing mice.

Animals↗
PubMed2002

Expression and mutation of p53 gene in the lung of mice intratracheal injected with crystalline silica.

The genotoxic effect of crystalline silica (Qt) in the lung was studied to clarify that silicosis conferred a significant increase in risk subsequent lung cancer. C57BL/6N mice received a single tracheal injection of Qt at dose of 2 mg/mouse. Lung p53mRNA was suppressed significantly, but no change of p21mRNA 15 months after treatment. Mutation of p53 gene was not identified at 15 months in the Qt group. Silicotic lesions were observed in the lungs of Qt group, but silicosis with pulmonary neoplasia was no detected. These results indicated that genetic changes in the silicotic lung might lead to facilitation of carcinogenesis.

Animals↗
PubMed2002

Expression of cyclooxygenase 2 and cytosolic phospholipase A(2) in the liver tissue of patients with chronic hepatitis and liver cirrhosis.

Cyclooxgenase (COX) and phospholipase A(2) (PLA(2)) are crucial rate-limiting enzymes involved in the conversion of arachidonic acid to prostaglandin H(2), the precursor of various compounds including prostaglandins (PGs), prostacyclin, and thromboxanes in the process of PGs' synthesis. Recent studies have shown increased levels of COX(2) in adjacent cirrhotic tissue of hepatocellular carcinoma. The relationship between the expression of COX(2) or cytosolicPLA(2) (cPLA(2)) and liver fibrosis has not been described previously. We used 45 formalin-fixed, paraffin-embedded liver tissue samples obtained by needle biopsies from patients with chronic hepatitis, consisting of 7 cases of F(0), 10 cases of F(1), 10 cases of F(2), 9 cases of F(3) and 9 cases of liver cirrhosis (LC) according to the New Inuyama Classification of the staging of liver fibrosis. The expression of COX(2) and cPLA(2) was investigated by immunohistochemistry, western blotting and image analysis. The positive signals for COX(2) and cPLA(2) were observed in the cytoplasm of hepatocytes. The signal intensity of COX(2) increased significantly with the progression of liver fibrosis (P<0.001) and no significant difference was observed in the relative amount of cPLA(2) from group F(0) to group LC. According to the New Inuyama Classification of hepatitis activity grading, 45 samples were classified as group A(1) (23 cases), group A(2) (19 cases) and group A(3) (3 cases). No significant differences were found in the relative amount of COX(2) and cPLA(2) between group A(1) and group A(2-3). Significant correlation was observed between the relative amount of COX(2) and hyaluronan (P<0.01). Our findings suggested that COX(2) may be involved in liver fibrogenesis.

Journal Article↗