[A case of gastro-renal-shunt induced non-cirrhotic recurrent hepatic encephalopathy effectually treated by balloon-occluded retrograde transvenous obliteration].
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Balloon Occlusion↗
Biomedical subjects
S Hasumura
Publications and source records attributed to S Hasumura.
Involvement of insulin-like growth factor binding protein-3 in the retinoic acid receptor-alpha-mediated inhibition of hepatocellular carcinoma cell proliferation.
We examined the relationship between the expression of retinoic acid receptor-alpha (RAR-alpha) and upregulation of insulin-like growth factor binding protein-3 (IGFBP-3) in the retinoid-induced inhibition of hepatocellular carcinoma (HCC) cell proliferation. HCC cell lines showed a marked expression of RAR-alpha, whereas the expression levels of RAR-beta and RAR-gamma were relatively lower. An RAR-alpha agonist significantly inhibited the HCC cell proliferation both in vitro and in vivo. The RAR-alpha expression closely related to the upregulation of IGFBP-3 as compared with RAR-beta or RAR-alpha expressions. RAR-alpha agonist would be beneficial to inhibit the growth of HCC.
Animals↗
Developments in bioartificial liver research: concepts, performance, and applications.
As an alternative to liver transplantation, numerous researchers have been working toward the goal of development of a fully functional artificial liver. In recent years, artificial liver support systems have been advocated as interim treatments for patients awaiting hepatocyte replacement therapy or liver transplantation; so-called "bridging" treatments. It is recognized that an effective artificial liver system requires: (1) a viable and highly functional hepatocyte cell line, (2) a suitable bioreactor environment and peripheral control systems, and (3) an effective extracorporeal circulatory system to incorporate an artificial liver system. Conventional systems have, however, suffered from various drawbacks, including incompatibility of cell cultures derived from non-human cells, insufficient cell proliferation, rapid deterioration of cellular function due to an impoverished cellular environment, and lack of system scalability. A newly established artificial liver system overcomes many of these problems and demonstrates a long-term capacity to maintain multiple liver-specific functions, such as protein synthesis, enzyme activity, and drug metabolism, both quantitatively and qualitatively. The present review provides an overview of the concepts underpinning artificial liver systems, the performance of presently available systems and the practical applications of available systems and those in development.
Animals↗
Invasiveness of hepatocellular carcinoma cell lines: contribution of membrane-type 1 matrix metalloproteinase.
Intrahepatic metastasis is one of the malignant features of hepatocellular carcinoma (HCC). Matrix metalloproteinases (MMPs) and urokinase-type plasminogen activator (u-PA)/plasmin, are known to be associated with the invasive properties of various types of tumor cells. In this study, we examined which proteinases play a role in the metastatic invasion of human HCC cell lines. JHH-5 and JHH-6 cells constitutively expressed mRNAs for both membrane-type 1 matrix metalloproteinase (MT1-MMP) and u-PA and invaded through reconstituted MATRIGEL in vitro, whereas JHH-7 cells expressed u-PA mRNA but not MT1-MMP and did not invade. However, hepatocyte growth factor (HGF) induced MT1-MMP expression on the surface of JHH-7 cells and markedly increased invasiveness of JHH-7 in a concentration-dependent manner. Moreover, cleavage activity for pro-MMP-2 was induced in HGF-treated JHH-7 cells. MMP inhibitor, rather than serine proteinase inhibitor, potently inhibited HCC cell invasion. Intrahepatic injection of HCC cell lines into athymic nude mice caused visible intrahepatic metastases in vivo. Moreover, JHH-7 tumors showed expression of MT1-MMP mRNA, while in vitro cultured JHH-7 cells did not. These findings suggest that MT1-MMP plays an important role in the invasive properties of HCC cells, and that HGF modifies the invasive properties of noninvasive HCC cells.
Animals↗
Retinol esterification activity contributes to retinol transport in stellate cells.
The mechanisms of retinol transport and accumulation in hepatic stellate cells (HSC) remain to be elucidated. Our previous studies suggested that retinol esterification activity, particularly lecithin:retinol acyltransferase (LRAT) activity, in liver retinoid metabolism is important to elucidate the relationship between retinol uptake by HSC and the esterification of retinol. In the present study, using a human HSC-like cell line, LI90, we demonstrated that retinol esterification activity of LI90 cells is similar to that of primary cultures of rat HSC and higher than that of a human hepatoma cell line. Further, since progesterone or diphospho-lauroyl-phosphatidylcholine increased retinol esterification activity of LI90 cells, it is likely that LRAT contributes to retinol esterification in LI90. We examined retinol esterification in LI90 cells and clearance of retinol from culture medium. The percentages of both retinol and esterified retinol in LI90 cells increased in a manner dependent on retinol concentration in medium, whereas that of retinol in medium decreased. The percentages of esterified and unesterified retinol in LI90 cells and of retinol in medium were linearly dependent on the logarithm of the initial concentration of retinol in the medium. These results suggest that retinol esterification activity contributes to retinol uptake by HSC and maintenance of non-toxic retinol levels in plasma.
Actins↗
Massive culture of human liver cancer cells in a newly developed radial flow bioreactor system: ultrafine structure of functionally enhanced hepatocarcinoma cell lines.
With a view to initiating clinical trials, cell morphology and function for a newly developed artificial liver support system employing highly functional human liver cell line, FLC-7, cultured in a radial flow bioreactor were compared to cells grown in a conventional monolayer culture. The radial flow bioreactor consists of a vertically extended cylindrical matrix comprised of porous glass bead microcarriers through which liquid medium flows from the periphery in toward the central axis generating a beneficial concentration gradient of oxygen and nutrients, while preventing excessive shear stresses or buildup of waste products. The three-dimensional culture system supports high-density (1.1 x 10(8) cells/ml-matrix), large scale cultures (4.4 x 10(10) cells/400 ml-bioreactor) with long-term viability. Scanning and transmission electron microscopy (SEM and TEM) revealed that cells cultured in a monolayer system were flattened and extended with numerous cytoplasmic projections. Cells in the three-dimensional culture were spherical and covered with microvillilike processes resembling liver cells in vivo. The cells were solidly attached on the surfaces and within the pores of the microcarriers in highly dense colonies. The spherical cells remained in close contact with adjacent cells, while circulation of liquid medium flowed freely through spaces between cells. FLC-7 cells produced albumin at a rate of 6.41 micrograms/24 h/10(6) cells. Alpha-fetoprotein (AFP) production dropped nearly threefold in comparison to monolayer cultures. Results demonstrated that the new artificial liver support systems (ALSS) provides a superior three-dimensional culture environment that allows cells to perform at naturally functioning levels.
Bioreactors↗
High density culture of immortalized liver endothelial cells in the radial-flow bioreactor in the development of an artificial liver.
Liver endothelial cells are important components of the tissue along the hepatic sinusoid. They are responsible for microcirculation in the liver and scavenger functions. It would therefore be important to include these cells in any hybrid type of artificial liver in addition to hepatocytes. However, it is difficult to culture these cells in vitro. The development of a liver endothelial cell line, which maintains the characteristics of the primary culture, would thus be of great benefit in the development of an artificial liver. In the present study we established immortalized liver endothelial cells from the liver of an H-2Kb-tsA58 transgenic mouse, which harbors the SV40 TAg gene. Hepatic sinusoidal cells isolated from H-2Kb-tsA58 mouse proliferated in the presence of gamma-interferon at 33 degrees C. Four clones were established, out of which clone M1 had the highest amounts of PGI2 production, as well as plasminogen activator activity and internalized acetylated low density lipoprotein. On culture dishes the M1 cells grew individually and spread. Sieve plates on the cell surface were not readily visible, but small pores were detected under electron microscopic observation. These results suggest that M1 clone cells originated from liver endothelial cells. Moreover it was possible to culture the immortalized liver endothelial cells in a radial-flow bioreactor for 5 days, with a maximum 6-keto prostaglandin F1alpha production of 25 microg per day. This suggests that immortalized liver endothelial cells and a radial-flow bioreactor can prove useful tools in the development an artificial liver.
Animals↗
[Work intensity during working hours and different types of care done by special nursing home workers].
This study was done to estimated work intensity during working hours and different types of care to obtain basic data for making a care program. The subjects were care workers in good health (n = 8, 24-45 years) who worked in a special nursing home. The estimated maximal oxygen intake level, which is the maximal aerobic capacity, of each subject was assessed as normal to very good. The energy expenditure was 1787 +/- 534kcal during working hours. The work intensity was 0.061 +/- 0.011kcal/kg/min, 2.7 +/- 0.7RMR, 98 +/- 6beats/min, and 30.3 +/- 2.0% VO2max. Among the duties assessed for work intensity, bathing had the highest intensity, followed by transferring, changing diapers, feeding, and dressing. The work intensity of bathing was 0.081 +/- 0.31kcal/kg/min, 3.9 +/- 1.0RMR, and 40.0 +/- 6.1 VO2 max, which was significantly higher than feeding, dressing, and transferring(p < 0.05). Care giving at the time of bathing was significantly longer than the other care types (p < 0.05). Feeding and transferring by inexperienced care workers were significantly low intensity (p < 0.05). Work intensity of care was at high levels within the maximal permissible level in which fatigue doesn't make an appearance during working hours and in five types of care. Furthermore, care work intensity increased according to a decrease in the ADL level among the elderly. It is concluded that when making a care program, it is important to consider the ADL level of the elderly, work intensity and the amount of care-giving time, not only to maintain the health of care workers, but, also, to give superior quality care to the elderly.
Activities of Daily Living↗
Intraocular hemorrhage developing during interferon therapy.
A 43-year-old man with chronic active hepatitis C was treated with interferon-beta (IFN-beta) at a dosage of 6 x 10(6) IU/day for a planned 6-week period. Ocular hyperemia, ophthalmalgia, and increased intraocular pressure in the right eye developed 20 days after the start of treatment. Intraocular pressure remained high, even after discontinuation of IFN therapy, laser therapy, and iridectomy. Two days later, the right eye was removed because perforation had occurred. The ocular symptoms that developed in this case were thought to have been caused and exacerbated by IFN administration.
Adult↗
[A new liver support system composed of functional human cells and a radial-flow bioreactor].
An artificial liver will be useful for the treatment of acute hepatic failure and a bridge of liver transplantation. The current reports suggest that the hybrid type of artificial liver composed of functional human liver cells and a bioreactor is practical for clinical use. In the present study, we succeeded high density culture on a large-scale of human functional hepatoma (JHH-7) using a newly developed radial flow packed-bed bioreactor. Since the shear stress of this bioreactor is lower than the other type, high density culture without cell damage is possible. JHH-7 cells produced large amounts of human albumin and other liver specific proteins, and then have the function of ammonia metabolism in the system. This study suggests that a radial flow bioreactor will be developed as a new type of artificial liver.
Albumins↗
Retinol transport in cultured stellate cells of rat liver: studies by light and electron microscope autoradiography.
The mechanisms of specific transport of retinoids into stellate cells (SC) of liver remain to be elucidated. In the present study, we have conducted experiments to observe the intracellular retinoid metabolism of cultured SC of rat liver using light and electron microscope autoradiography (LMARG and EMARG). After 72 h of culture, the cells were incubated in the medium containing 1.06 x 10(-6) or 6.36 x 10(-8) M of [3H]retinol for either 5 or 30 min. In some cases, incubation with the labeled retinol was followed by a medium containing nonlabeled 1 x 10(-6) M retinol for 90 min. First, the incorporation of labeled retinol (1.06 x 10(-6) M) into SC and hepatocytes was compared by LMARG. After 5 min, silver grains were already present on both cells. After 30 min, label was concentrated on the lipid droplets of SC. After the chase, the number of grains on hepatocytes decreased. On the other hand, grains on the lipid droplets of SC remained. Second, we studied the fine morphology and intracellular retinoid metabolism in SC using EMARG. The SC, which contained abundant multivesicular bodies (MVB) and lamellar bodies, were found to have a heavy accumulation of grains. Even in the medium containing a lower concentration of retinol (6.36 x 10(-8) M), SC also took up retinol. After 90 min of chase, many grains moved on the lipid droplets in SC. The labeled MVB were often accompanied by lamellar bodies and found near the lipid droplets. Sometimes we noticed small labeled lipid droplets bound by membranes in MVB. From the results of this study, we concluded that the MVB and lamellar bodies might be important organelles for retinyl ester formation and the initial storage of retinoid in the lipid droplets in SC.
Animals↗
Regulation of vitamin A transport into cultured stellate cells of rat liver: studies by anchored cell analysis and sorting system.
Stellate cells (SC) in the liver store the most retinoid in the body, but the mechanisms of specific retinoid transport into SC remain to be elucidated. In this study, to analyze the retinoid content of cultured SC, we employed an anchored cell analysis and sorting system (ACAS), which provides fluorescence analysis of single cultured cells under the phase-contrast microscope by utilizing a laser. First, we examined the effect of retinol binding protein (RBP) on retinol transport into cultured SC of rat liver. Rat holo-RBP added to the medium inhibited retinol uptake into SC. We also prepared RBP-free human serum by affinity chromatography using conjugated anti-human RBP IgG and compared retinoid fluorescence of SC cultured in human serum with or without RBP. No significant difference in retinoid fluorescence intensity was observed between SC cultured with and without holo-RBP. Second, the removal of cellular retinol by esterification may be important for the continued uptake of retinol. Retinyl esters are stored in lipid droplets of SC. Therefore we examined the relationship between the lipid droplet number and the retinoid fluorescence intensity in SC which were cultured in medium containing retinol for 1-3 days. The increases in lipid droplet number and in retinoid fluorescence in SC were almost parallel. Progesterone, previously shown to increase the esterification of retinol by lecithin:retinol acyltransferase (LRAT) in vitro, was added to the SC medium; progesterone facilitated retinol uptake in cultured SC. In conclusion, RBP did not facilitate specific retinol transport into SC. However, the specific transport of retinol is likely to be dependent on the intracellular esterification of retinol by LRAT in SC.
Animals↗
[Consideration on the mechanism of liver regeneration on experimental results].
Liver has enough functional capacity and regeneration ability. Liver parenchymal cells are usually stable, and it is thought being at stage of Go in cell cycle. But liver cells are easily into progressive stage and the liver recovers its functions and volume after partial hepatectomy or liver injury. Usually the studies of liver regeneration are done by studying control of growth of isolated hepatocytes in primary culture in vitro, and by pathological considerations of experimental injured models of liver in vivo. In this paper, we considered known several hepatotrophic factors including our experimental results, and regeneration mechanisms by noticing appearance of albumin positive hepatocytes in injured Nagase analbuminemic rat (NAR).
Aging↗
Integration of hepatitis B virus DNA into cells of six established human hepatocellular carcinoma cell lines.
The authors successfully established 5 hepatocellular carcinoma cell lines, JHH-1, 2, 4, 5 and 6, derived from hepatitis B surface antigen seronegative patients and one line. JHH-7, from a patient considered to be a hepatitis B virus carrier. In the culture media of any of the JHH cell lines, including JHH-7, hepatitis B surface antigen was not detected by radioimmunoassay. However, in JHH-7, integration of hepatitis B virus DNA was confirmed at two sites on the chromosomes of this line by Southern blot hybridization. In contrast, in other JHH cell lines derived from hepatitis B surface antigen seronegative patients, integration of hepatitis B virus DNA into the chromosomes of cells was not detected. These cell lines will be useful in the investigation of hepatocellular carcinoma development, especially for research into non-A/non-B hepatitis viruses.
Albumins↗
[Establishment and characterization of a human hepatocellular carcinoma cell line JHH-7 producing alpha -fetoprotein and carcinoembryonic antigen--changes in secretion of AFP and CEA from JHH-7 cells after heat treatment].
A human hepatocellular carcinoma cell line, JHH-7, was established from resected liver tumor of a 53 year old male with hepatitis B virus infection. JHH-7 was composed of polygonal epithelial cells and functionally synthesized and secreted human albumin, AFP, CEA and ferritin. No HBsAg was detected in the culture supernatant of JHH-7 cells. Changes of secretion of AFP and CEA from JHH-7 cells after heat treatment was studied using a temperature gradient incubator. Secretion of AFP decreased along with the inhibition of cell proliferation by heat treatment. Secretion of CEA, however, did not decrease even though the cells were damaged.
Biomarkers, Tumor↗
[Analysis for the integrated hepatitis B virus genome in cells of established human hepatocellular carcinoma cell line JHH-7].
Authors have successfully established 7 human hepatocellular carcinoma (HCC) cell lines. In one of these cell lines, JHH-7, derived from HBs antigen positive HCC, hepatitis B virus (HBV) genome was analyzed by Southern blot hybridization. Digesting with Hind III restriction endonuclease, two bands were obtained at 6.0 and 2.5 kb, that is the integration of HBV genome was confirmed at the two sites of chromosomes in this cell line. And analyzing with 32P labeled HBV-DNA fragments for probes, it was indicated that integrated HBV genome was incomplete one containing from X to C region.
Blotting, Southern↗
Morphological characteristics of human fat-storing cells fractionated and cultured by newly techniques.
Human non-parenchymal cells, especially fat-storing cells (FSCs), were isolated and primarily cultured using 1-2 g of normal human liver tissue obtained in conjunction with tumor biopsies. The human hepatic FSCs were cultured by a modified Howard and Pesch method. Microscopically the cultured human FSCs showed characteristic fat droplets like those in in vivo FSCs. The FSCs from tumor liver with serious fibrosis contained fewer fat droplets, and the fibrous constituents were especially abundant. The intermediate filaments extending longitudinally were characteristic of the cultured FSCs. In the human FSCs observed by the plasma polymerization replica method, the cells adhered and were stretched relatively thin. Particularly, the ends of the processes adhered and stretched like a folding fan to the bottom of the dish.
Adipose Tissue↗
[Combination therapy of hyperthermia and other methods in liver and bile tract cancers--evaluation of these methods using cancer cell lines in vitro].
In order to evaluate the combination therapy for liver and bile tract cancer, the effects of anticancer drugs and hyperthermia were observed using cultured human cancer cell lines. In the case of gall bladder cancer cell line (NOZ), combination of adriamycin and hyperthermia showed more effective inhibition for cell proliferation than MMC + hyperthermia and 5-FU + hyperthermia. Hepatocellular carcinoma cell line (JHH-4) showed remarkable inhibition of cell growth and secretion of albumin by combination treatment of adriamycin and hyperthermia. Morphologically, JHH-4 cells were enlarged and the nucleus was also enlarged with combination adriamycin and hyperthermia by phase contrast microscopy. Cytoskeleton of JHH-4 cells became irregular and intercellular borderline was unclear by plasma polymerization replica method (PPRM). The effects of BRM (OK-432 and TNF) on HCC cell lines was also investigated. OK-432 directly inhibited proliferation of JHH-4 cells. We observed internalization of OK-432 by JHH-4 cells with TEM and 16-mm movie. TNF showed various effects on human HCC cell lines. Proliferation of two cell lines was inhibited, and one tended to be enhanced after the addition of TNF to the medium. Hyperthermia influenced the effects of TNF to HCC cell lines. We think that this paper is a very significant study for improving the therapy for hepato-biliary cancers.
Antineoplastic Agents↗