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Biomedical subjects

T Saibara

Publications and source records attributed to T Saibara.

At least 73 records · Page 4Linked to original sources
PubMed1994

Immunological functions of mouse liver resident high density lymphocytes.

Liver-derived high density lymphocytes (Matsunaga cells) have been detected as members of resident T cells in the mouse liver. In this study, we assessed the immunological functions of liver-derived high density lymphocytes of BALB/c mice in comparison with those derived from spleen and peripheral blood. Liver-derived high density lymphocytes proliferated in response to the syngeneic and allogeneic mixed lymphocyte reaction, as well as those derived from spleen and peripheral blood. The allo-activated cytotoxic T lymphocyte activity of liver-derived high density lymphocytes against PHA-blasts of C57BL/6 mice was lower than that of spleen- and peripheral blood-derived lymphocytes. The suppressor activity of syngeneic- or allo-activated high density lymphocytes of the liver, spleen, and the peripheral blood was assessed by measuring their suppressive effect on the proliferation or on the generation of allo-specific cytotoxic activity in allogeneic mixed lymphocyte reaction. The suppression was concentration-dependent and strongest in liver-derived lymphocytes.

Animals↗
PubMed1994

Dysfunction of mouse liver mitochondria induced by 2,2'-azobis-(2-amidinopropane) dihydrochloride, a radical initiator, in vitro and in vivo.

Mouse liver mitochondria were uncoupled in a time dependent by intraperitoneal injection of a radical initiator, 2,2'-azobis-(2-amidinopropane) dihydrochloride (AAPH) (100 mg/kg). State 3 respiration, ADP/O ratio and respiratory control ratio (RCR) were decreased 30 min after injection but there was no effect on state 4 respiration. Lipid peroxidation was increased and oxidative phosphorylation was uncoupled at one hr after drug injection but gradually recovered to normal levels after 14 hr in vivo. State 3 respiration, RCR and ADP/O ratio but not state 4 respiration of isolated mouse mitochondria were inhibited by short term incubation with AAPH in vitro. This inhibitory action was concentration dependent (ID50 = 5 mM) but was not prevented by alpha-tocopherol. AAPH had no effect on electron transport or the membrane potential of these isolated mitochondria. However, mitochondria were uncoupled via lipid peroxidation and swelling by long term incubation with AAPH. These inhibitory effects of AAPH were reduced by its spontaneous degradation not only in vitro but also in vivo. Thus AAPH induces mitochondrial dysfunction by direct action in the early period of treatment and free radicals produced from AAPH mediate mitochondrial swelling via lipid peroxidation in the late period. From these findings, it is concluded that mitochondrial phosphorylation plays an important role in the pathogenesis of liver injury induced by AAPH and that radicals generated by AAPH might be a source of liver injury and mitochondrial dysfunction in vivo.

Amidines↗
PubMed1994

Serum alpha-L-fucosidase activity and tumor size in hepatocellular carcinoma.

The serum level of alpha-L-fucosidase activity has been suggested as a useful marker in the diagnosis of hepatocellular carcinoma, although the precise mechanism behind the elevation of this parameter has not been determined. We found that the serum alpha-L-fucosidase activity level was significantly higher in 67 patients with hepatocellular carcinoma (695.1 +/- 245.5 nmol/ml/hr) than in 47 patients with cirrhosis (389.1 +/- 188.2 nmol/ml/hr; p < 0.001) and in 54 controls (202.0 +/- 104.6 nmol/ml/hr; p < 0.001). However, alpha-L-fucosidase activity was not correlated with tumor size (r = 0.134), whereas the alpha-fetoprotein level was correlated with tumor size (r = 0.580, p < 0.001). When 515.8 nmol/ml/hr was taken as the cutoff value (mean value in the controls plus 3 standard deviations), alpha-L-fucosidase activity was above the cutoff value in 12 of the 17 patients with a hepatocellular carcinoma less than 2 cm in diameter, in 28 of the 37 patients with a hepatocellular carcinoma less than 3 cm in diameter and in 52 of the 67 patients with hepatocellular carcinoma. In contrast, only 10 of the 47 patients with cirrhosis had levels above the cutoff value. These findings suggest that an increase in serum alpha-L-fucosidase activity in patients with cirrhosis may be a marker for detecting a hepatocellular carcinoma, especially a small tumor, because alpha-fetoprotein and des-gamma-carboxy-prothrombin are less promising as tumor markers.

Biomarkers↗
PubMed1994

Appearance of sinusoidal inclusion-containing endothelial cells in liver disease.

Sinusoidal "inclusion-containing endothelial cells" were studied histopathologically and immunohistochemically in various liver diseases, and their clinical importance was investigated. A total of 498 needle liver biopsies were examined. Endothelial inclusions inside the cells were recognized as eosinophilic granules in hematoxylin-eosin-stained sections. Electron microscopy showed that these inclusions corresponded to round cytoplasmic dense bodies with a single limiting membrane. The contents of these bodies were generally homogeneous, but sometimes heterogeneous. The inclusions appeared to contain protein, but were resistant to trypsin digestion, and immunohistochemistry failed to identify any immunoglobulins or hepatocyte-derived proteins. These endothelial cells also contained an increased number of micropinocytotic vesicles when compared with ordinary cells. The inclusion-containing endothelial cells appeared frequently in chronic hepatitis, but were relatively rare in other liver diseases. The incidence was higher in chronic aggressive hepatitis than in chronic persistent hepatitis or inactive cirrhosis. Although the density of these cells varied considerably even among patients with the same histological diagnosis and the phenotypical changes of these endothelial cells, assessed by monoclonal antibodies, were not apparent, the serum gamma globulin level tended to increase in relation to the density of inclusion-containing endothelial cells and the correlation was significant in hepatitis C.

Chronic Disease↗
PubMed1994

Acute hepatic failure with swollen mitochondria and microvesicular fatty degeneration of hepatocytes triggered by free radical initiator.

BACKGROUND: Reye syndrome and acute fatty liver of pregnancy are characterized by acute hepatic failure associated with characteristic pathologic changes of hepatocytes, i.e., microvesicular fatty degeneration with severe mitochondrial swelling. Several animal models of these conditions have been proposed, although none has demonstrated sufficiently similar laboratory and pathologic features. EXPERIMENTAL DESIGN: A single dose of 2,2'-azobis-(2-amidinopropane) dihydrochloride, a free radical initiator, 100 mg/kg of body weight, injected intraperitoneally to BALB/c mice induced a transient decrease in hepatic energy charge, liver mitochondrial respiratory activity, and succinate dehydrogenase activity and a transient increase in blood ammonia level, suggesting hepatic failure. RESULTS: The hepatocytes displayed microvesicular fatty degeneration with severely swollen mitochondria. CONCLUSIONS: This is the first model of acute hepatic failure with microvesicular fatty degeneration of hepatocytes. It suggests a role of free radicals in the pathogenesis of certain types of acute hepatic failure.

Adenine Nucleotides↗
PubMed1993

Participation of cathepsin B in processing of antigen presentation to MHC class II.

Cellular and humoral immune responses to vaccines of hepatitis B type and rabies were inhibited by specific inhibitors of cathepsin B, specific synthetic substrates of cathepsin B and anti-cathepsin B antibody. Therefore the lysosomal cathepsin B of antigen presenting cells plays an essential role in processing of these antigens for presentation to MHC class II. One of the active sites of cathepsin B, VN217-222 shares highly homologous sequences with a part of the desetope, a binding domain of antigenic peptides, VN57-62 of MHC class II, beta-chain. This evidence suggests that the peptides processed by the substrate specificity of cathepsin B exhibit a common affinity to bind with the desetope of MHC class II, beta-chain.

Amino Acid Sequence↗
PubMed1993

Depressed immune functions in the early phase of varicella-zoster virus reactivation.

Varicella-zoster virus (VZV) infections are among the most common viral diseases characterized by recurrent episodes alternating with asymptomatic periods. VZV reactivation is believed to be induced by the impairment of the host's cell-mediated immune system; however, the precise mechanisms involved in the latency period and reactivation of herpes viruses in the infected host are not yet fully elucidated. We assessed the immune functions in noncompromised patients with typical herpes zoster to investigate the immunological status during the process of reactivation of VZV. The results indicated depressed immune functions in the early stage of VZV reactivation with gradual improvement during the recovery phase. These findings are in accord with the clinical course of herpes zoster and suggest a possible therapeutic trial.

Adult↗
PubMed1993

Long-latency event-related potentials in acute hepatitis patients with severe coagulopathy.

In 19 acute hepatitis patients with severe coagulopathy who were fully alert and oriented without any changes of mood or behavior, the P300 latency and the arterial blood ketone body ratio (KBR) were assessed as predictors of fulminant hepatitis. All 5 patients developing fulminant hepatitis had a corrected P300 latency longer than 345 msec and 4 of them had a KBR below 0.6. There was a significant negative correlation between the KBR and the blood ammonia level and between the KBR and the corrected P300 latency, while there was a positive correlation between the blood ammonia level and the corrected P300 latency. These data suggest that hepatic encephalopathy develops when loss of hepatic detoxifying activity allows toxic substances to reach the brain and induce cerebral edema. Our findings also suggest the clinical value of using the P300 latency combined with the KBR as predictors of fulminant hepatitis.

Acoustic Stimulation↗
PubMed1993

Cytotoxic activity of spleen-derived T lymphocytes against autologous biliary epithelial cells in autopsy patients with primary biliary cirrhosis.

Autoimmunity against biliary epithelial cells is considered to be involved in the pathogenesis of primary biliary cirrhosis (PBC). However, cytotoxic activity of T lymphocytes against biliary epithelial cells has not previously been examined. This study has demonstrated that spleen-derived T lymphocytes were cytotoxic for autologous biliary epithelial cells in all of five patients with PBC, even though it was only detectable at high effector to target ratios. Such cytotoxicity was not found in non-PBC patients. CD8-positive T lymphocytes were shown to be responsible for the cytotoxicity by negative selection, and its inhibition was dependent on the ratio of cold to hot target cells. These observations may support a current hypothesis that the pathogenesis of PBC is partly due to T cell autoimmunity directed against the bile duct epithelium.

Aged↗
PubMed1993

Assessment of lymphokine-activated killer activity and gamma-interferon production in patients with small hepatocellular carcinomas.

We have previously reported depressed gamma-interferon production and depressed lymphokine-activated killer and natural killer activity in patients with relatively large hepatocellular carcinomas. These parameters were normal in cirrhosis. Some evidence had suggested a gamma-interferon production defect as the main cause of depressed lymphokine-activated killer activity in hepatocellular carcinoma, (i.e., gamma-interferon enhances lymphokine-activated killer and natural killer activity and gamma-interferon antibody inhibits lymphokine-activated killer induction). However, we were unable to clinically define the precise mechanism operating here because gamma-interferon production and lymphokine-activated killer activity were both defective in advanced hepatocellular carcinoma. In recent years, it has become possible to detect even small hepatocellular carcinomas on ultrasonography and to confirm them by fine-needle biopsy. In this study, we assessed those immune parameters in 48 patients with hepatocellular carcinomas less than 2 cm in diameter to confirm depressed immune function and to clarify the mechanism of these defects. Lymphokine-activated killer activity was defective in 31 patients (64.6%), whereas gamma-interferon production was defective in only 1 of these patients (2.1%). This observation argues against the hypothesis that defective gamma-interferon production is the primary defect and provides new insight into the mechanism of progression of defective immune function in hepatocellular carcinoma. Thirty-one of the 48 hepatocellular carcinoma patients were treated surgically, and these immune parameters were followed for 6 mo. The recovery of lymphokine-activated killer activity in all hepatocellular carcinoma patients with low lymphokine-activated killer activity suggests the tumor burden as the cause of defective lymphokine-activated killer activity.

Adult↗
PubMed1993

Depressed immune function in patients with cirrhosis before emergence of hepatocellular carcinoma.

Hepatocellular carcinomas 1 cm in diameter with high or low echogenicity can be detected on ultrasonography and confirmed on fine-needle biopsy, but it is still very difficult to detect small hepatocellular carcinomas with isoechogenicity. In this study, we assessed lymphokine-activated killer cell activity and interferon-gamma production prospectively every 1 to 3 mo for 23 +/- 4 mo (mean +/- 1 S.D.) in 227 patients with cirrhosis. Transient depression of lymphokine-activated killer activity was detected in 43 patients (defective lymphokine-activated killer group), and hepatocellular carcinoma was detected in 24 cases before the end of the 18-mo follow-up. Twenty-one (87.5%) of the 24 hepatocellular carcinoma patients were included in the defective lymphokine-activated killer group. Defective lymphokine-activated killer activity was detected more than 6 mo before detection of a space occupying lesion in the liver or elevation of alpha-fetoprotein level above 400 ng/ml. Serum alpha-fetoprotein level was elevated above 400 ng/ml in only five cases in which hepatocellular carcinoma was detected as a space-occupying lesion. Our results indicate that sequential assessment of lymphokine-activated killer activity may be a predictor of hepatocellular carcinoma and that the depression of immune function in cirrhotic patients is a serious risk factor for hepatocellular carcinoma emergence.

Adult↗
PubMed1993

[Recent studies on Ito cells with molecular biology].

By Northern blot analysis of total RNA, extracted from normal human and rat Ito cells, either freshly isolated or in culture, recent studies demonstrated the expression of mRNA for collagen type I, III, IV, fibronectin, laminin, transforming growth factor-beta (TGF-beta), hepatocyte growth factor, nuclear retinoic acid receptor-beta and alpha-smooth m muscle actin. Moreover, Ito cells isolated from experimentally induced fibrotic livers exhibited a marked increase in mRNA for collagen type I, associated with a moderate increase in mRNA of collagen type III and TGF-beta. Although endothelial cells from the same liver also showed moderate increase in mRNA for collagen type I alone, hepatocytes showed no changes. From these results it is concluded that Ito cells are the most important cells in hepatic fibrogenesis.

Animals↗
PubMed1992

Binding of T cell receptor to major histocompatibility complex class II-peptide complexes at the single-cell level results in the induction of antigen unresponsiveness (anergy).

Using dispersion cultures performed in semi-solid medium we demonstrate here that the interaction of T cell antigen receptor molecules with Ia-peptide complexes on the same cell surface results in T cell activation, without the production of lymphokines. This recognition of antigen at the single-cell level, induced a state of anergy which was not due to a decrease of surface T cell antigen receptor/CD3 complexes. The induction of anergy by peptide could not be prevented by the addition of various co-stimulatory signals, including antibodies to CD28, or CD2, high doses of interleukin-2 or phorbol ester.

Amino Acid Sequence↗
PubMed1992

Administration of interleukin-2 induces major histocompatibility complex class II expression on the biliary epithelial cells, possibly through endogenous interferon-gamma production.

In various organ-specific autoimmune diseases, aberrant expression of major histocompatibility complex class II antigens on each target epithelial cell has been reported. Some researchers have attempted to link this phenomenon to the antigen-presenting capacity and the induction of autoimmunity, whereas others think it might serve as a peripheral mechanism for the induction and the maintenance of self-tolerance in autoreactive T cells. In this study, we showed that intraperitoneal administration of interleukin-2 (1.2 x 10(6) IU/kg) to 4-wk-old male BALB/c mice for 35 consecutive days induced lymphocyte infiltration around bile ducts in the liver and major histocompatibility complex class II expression on biliary epithelial cells, which was immunoelectron microscopically confined to the luminal cell surface. Immunohistochemically, lymphocytes accumulating around bile ducts were mainly T cells, positive for CD3, L3T4 and H-2 class II molecules, and a few of them were positive for Lyt-2 and negative for immunoglobulin. Half of the infiltrates were positive for asialo GM1, and one-third was positive for interferon-gamma. Interferon-gamma-positive, L3T4-positive cells were detected in mirror sections. However, neither the destruction of biliary epithelial cells nor the presence of granulomas was observed. Autoantibodies were serologically undetectable. The existence of interferon-gamma-positive cells in the lesion and the fact that intravenous administration of anti-interferon-gamma twice a week completely inhibited the lymphocyte infiltration and the major histocompatibility complex class II expression on biliary epithelial cells suggested that these changes were induced through endogenous interferon-gamma production.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Peptide-induced proliferation and lymphokine production in human T cells in the absence of antigen-presenting cells: role of T-cell activation state and costimulatory signals.

The role of T-lymphocytes as antigen-presenting cells (APCs) for other T cells was investigated. Activated rabies-virus-specific human T-cell clones were shown to present peptide to class II major histocompatibility complex (MHC)-restricted T cells of a different fine specificity, resulting in lymphokine production and cell proliferation. Furthermore, purified and activated antigen-specific T cells could produce lymphokines and proliferate as a result of the addition of antigenic peptide in the absence of APC. The functional response of T cells to peptide in the absence of APC was amplified by the addition of phorbol ester (PMA) and was inhibited with antibodies specific to class II MHC or to the CD2 molecule. Experiments performed in single-cell suspension cultures using semisolid medium prepared with 1% agar demonstrate that T-cell proliferative and lymphokine responses to peptide both in the presence and absence of APC require the interaction of T-cell antigen receptor (TCR) molecules with class II MHC-peptide complexes on different cell surfaces (cell-cell contact). On the other hand, peptide self-presentation, which occurs by the binding of TCR with class II MHC-peptide complexes on the same cell surface (at the single-cell level), resulted in T-cell activation (i.e., high expression of surface CD2, CD25, and HLA-DR molecules), without proliferation or lymphokine secretion, a pattern observed in the induction of T-cell anergy by antigen. The results are discussed in terms of the role of class II MHC molecules on activated T-lymphocytes, which enable these cells to function as "professional APC" in the development of T-cell regulatory networks.

Amino Acid Sequence↗
PubMed1992

Arterial blood ketone body ratio as a possible indicator for predicting fulminant hepatitis in patients with acute hepatitis.

Encephalopathy and severe coagulopathy in patients with acute hepatitis (AH) are good markers for the diagnosis of fulminant hepatitis (FH), which occurs in only about 1% of AH patients. However, even if patients show severe coagulopathy, it is quite difficult to predict FH before the onset of encephalopathy. The ratio of acetoacetate/beta-hydroxybutyrate in arterial blood (KBR) has been reported to reflect the cellular energy charge level in hepatocytes. In our previous report, KBR was quite low in FH patients and was an excellent marker for predicting the prognosis. KBR of normal subjects is distributed in a range of 1.0-2.1 (1.54 +/- 0.26, mean +/- SD). In this study, we assessed KBR serially in 15 AH patients with severe coagulopathy (hepaplastin test (HPT) < 40%), including seven patients who developed FH, to see if we could predict FH by using KBR as a marker. Seven patients with KBR < 0.6 of long duration (4 days or more) were complicated with hepatic encephalopathy (HE) and it took 3 or more days of KBR below 0.6 before HE appeared. The other eight patients with KBR < 0.6 of short duration (less than 4 days) were not complicated with HE. These data suggest that AH patients with HPT < 40% and a 3-day duration of KBR < 0.6 are at serious risk of FH.

Acute Disease↗
PubMed1991

Immunoelectron microscopic identification of asialo GM1-positive cells in adult rat liver.

For the electron microscopic identification of asialo GM1-positive cells, fresh-frozen sections fixed with cold acetone and PLP-fixed vibratome sections of adult rat livers were prepared immunocytochemically using the avidin-biotin-peroxidase complex method. Asialo GM1-positive cells were located mainly in the sinusoids, and rarely in Glisson's sheath and portal veins. In the sinusoids, most pit cells, showing the ultrastructural characteristics of large granular lymphocytes (LGL), were positive for asialo GM1 but a few pit cells were asialo GM1-negative. There were several, morphological differences between asialo GM1-positive and -negative pit cells. The asialo GM1-negative pit cells were smaller and had less-developed cell organelles and fewer dense granules, suggesting a more immature stage of development. Almost all the monocytes, segmented neutrophils and eosinophils, and small or large lymphocytes in the sinusoids also showed positive reaction for asialo GM1. In Glisson's sheath, in addition to pit cells and lymphocytes, mast cells were also positive for asialo GM1. In contrast, fixed cells such as liver parenchymal cells, endothelial cells, Kupffer cells and Ito cells within the liver lobules, as well as biliary epithelial cells, smooth muscle cells, fibroblasts, endothelial cells and pericytes in Glisson's sheath were all negative for asialo GM1. Thus, cell surface asialo GM1 expression is not specific for pit cells (LGL) in the rat liver.

Animals↗