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H Asakura

Publications and source records attributed to H Asakura.

At least 181 records · Page 10Linked to original sources
PubMed1998

[Collagen diseases and gastrointestinal bleeding].

The main lesion of the collagen diseases involves blood-connective tissue, so every collagen disease is a accompanied by gastrointestinal bleeding to some degrees. The concept of systemic vasculitis had been confused, but recently, the criteria for each disease has been established. In addition to these vasculitis, antiphospholipid syndrome, amyloidosis, NSAIDs, steroid and secondary infection caused by the use of immunosuppressant are the candidates for the cause of gastrointestinal bleeding in the collagen diseases. In this paper, we described concisely about the gastrointestinal bleeding in SLE, RA, and systemic vasculitis.

Anti-Inflammatory Agents↗
PubMed1998

[Efficacy of granisetron as anti-emetic agent for emesis induced by intra-arterial injection therapy for hepatocellular carcinoma].

The effect of granisetron in preventing nausea and emesis induced by intraarterial chemotherapy was comparatively studied with a historical control group (46 cases) in 50 patients with hepatocellular carcinoma receiving intraarterial anti-tumor drugs such as cisplatin and doxorubicin. Emesis was perfectly controlled in 39 out of 50 patients in the treatment group (78%), in comparison to 33 out of 46 patients (71.7%) in the historical control group. This represented no statistical significance between the two groups. In terms of the severity of nausea, however, the granisetron group demonstrated significant superiority to the control group with 27 out of 50 patients (54%) being free of symptoms compared with 16 out of 46 patients (34.8%) in the control group. A stratified analysis of the data also demonstrated significant superiority of the granisetron group over the historical group in the number of emetic episodes and the severity of nausea in female patients, who are more predisposed to emesis. The above results confirm the usefulness of granisetron as an antiemetic agent used for the prevention of acute nausea and emesis induced by intraarterial chemotherapy.

Adult↗
PubMed1997

Expression, localization and alternative splicing pattern of fibronectin messenger RNA in fibrotic human liver and hepatocellular carcinoma.

BACKGROUND/AIMS: Fibronectin is a multifunctional glycoprotein and plays important roles in cell-to-cell or cell-to-matrix interaction. The molecular and functional diversity of fibronectin arises from alternative splicing of pre-mRNA at three variable regions, termed ED-A, ED-B and IIICS. Cellular fibronectin with ED-A and ED-B regions has different biological activities from plasma fibronectin lacking these regions. This study was aimed at investigating the type-specific expression of fibronectin in human liver diseases. METHODS: Immunohistochemistry with anti-total and anti-cellular fibronectin monoclonal antibodies, in situ hybridization with cDNA probes detecting common and ED-A regions and RT-PCR to amplify each variable region were performed in 35 specimens, including 4 control, 16 chronic hepatitis, 7 liver cirrhosis and 8 hepatocelular carcinoma. RESULTS: In control liver, there were slight deposits of cellular fibronectin [ED-A(+)fibronectin] in portal areas. In chronic hepatitis, it was strongly deposited at the margin of the fibrously enlarged portal areas where new collagen fibers were formed. Cellular fibronectin was evenly and abundantly accumulated in fibrotic septa in liver cirrhosis, and in fibrotic septa and capsules of tumor nodules in hepatocellular carcinoma. In control liver, cellular fibronectin mRNA was localized in a few hepatocytes and non-parenchymal cells around central veins, and was increased in the same cell populations near fibrously enlarged portal areas as hepatic fibrosis progressed. In hepatocellular carcinoma, it was expressed in most hepatoma cells. Fibronectin mRNA with three variable regions was detectable by RT-PCR in control liver as well as in each disease group. CONCLUSIONS: The expression of cellular fibronectin was increased in fibrotic human liver and hepatocellular carcinoma. In human liver, both non-parenchymal cells and hepatocytes participated together in cellular fibronectin production. In hepatocellular carcinoma, hepatoma cells were the main producer. Our results indicate that, in human liver, cellular fibronectin may participate in the hepatic fibrogenesis and in the malignant phenotypes of hepatocellular carcinoma.

Alternative Splicing↗
PubMed1997

Amplification of BCR protein associated with oncogenesis in human hepatocellular carcinoma.

The BCR gene is located on human chromosome 22. The normal cellular BCR gene encodes a 160,000-dalton phosphoprotein associated with a serine/threonine kinase activity. The BCR protein is involved in signal transduction. We investigated the expression of the BCR protein in hepatocellular carcinoma (HCC), surrounding noncancerous liver tissue, liver cirrhosis (LC), chronic hepatitis (CH), and normal liver with immunohistochemistry and a western blot analysis. BCR immunoreactivity was detected using a monoclonal antibody. In normal liver, and both CH and LC without association of HCC, the immunoreactivity of the BCR protein was minimal. In contrast, 73% (22 of 30) of noncancerous liver tissue adjacent to the HCC and 40% (12 of 30) of HCC expressed BCR protein; this difference was statistically significant (P < 0.01). The expression of the BCR protein expression correlated with the degree of histological differentiation of HCC (P < 0.05). In addition, the amplification of BCR protein in noncancerous cells was supported by the detection of specific protein using a western blot analysis. In two cases, the expression of BCR protein occurred only in overtly malignant HCC cells. As a result, the expression of the BCR protein may be associated with oncogenesis in human HCC.

Aged↗
PubMed1997

Intravenous immunoglobulin (IVIG) treatment of experimental colitis induced by dextran sulfate sodium in rats.

We investigated the therapeutic effect and immunological action mechanism of IgG in experimental colitis induced by 3% dextran sulfate sodium in rats. Intravenous injection of homologous (rat) IgG (400 mg/kg per day) caused a significant suppression of occult blood discharge and ulcerative lesions in the colon, while no suppressive effect was observed in the case of heterologous (human) IgG. The positive effect of rat IgG on the lesions was also clearly shown by the histological examinations. Generation of proinflammatory cytokines, i.e. tumour necrosis factor-alpha (TNF-alpha) and IL-1alpha, in the lesions was found to be inhibited by administration of rat IgG. Little or no suppressive action was exerted by human IgG. Careful examination of recruited T cells and macrophages, both of which are thought to play important roles in the development of ulcerative colitis, indicated that rat IgG, but not its human counterpart, decreased the number of immunocompetent cells in colonic mucosa. Meanwhile, in an in vitro study, both forms of IgG were shown to suppress production of TNF-alpha and IL-1alpha from lamina propria mononuclear cells isolated from rat colon. These findings suggest that, mainly by suppressing recruitment of immunocompetent cells into the lesions, homologous IgG may reduce the occurrence of colitis.

Animals↗
PubMed1997

Preventive and therapeutic effects in rats of hepatocyte growth factor infusion on liver fibrosis/cirrhosis.

Liver fibrosis/cirrhosis is characterized by hyper-accumulation of fibrous tissue components and is commonly observed in later or terminal states of chronic hepatic diseases. In ongoing work, we found that the administration of human recombinant hepatocyte growth factor (hrHGF) suppressed the onset of liver fibrosis/cirrhosis in several distinct models and accelerated the recovery from liver fibrosis/cirrhosis in rats. Repeated administration of porcine serum for 10 weeks to rats induced liver fibrosis without any accompanying hepatocellular injuries; in addition, the intravenous (i.v.) administration of hepatocyte growth factor (HGF) to these rats suppressed increases in fibrous components and hydroxyproline contents in the liver, thus preventing the onset of liver fibrosis. Repeated administration of dimethylnitrosamine (DMN) for four weeks induced liver cirrhosis, as characterized by the hyper-accumulation of fibrous components, infiltration of mononuclear leukocytes, and hepatic dysfunction. When HGF was injected daily for four weeks along with DMN-treatment, the onset of DMN-induced hepatic fibrosis/cirrhosis was suppressed; the numbers of infiltrating mononuclear cells, fibrous tissue components, and hydroxyproline content in the liver were decreased. When HGF was injected for two weeks following four weeks of DMN-treatment, HGF accelerated the recovery from liver cirrhosis and prevented death due to hepatic dysfunction. Likewise, HGF-injection suppressed the onset of liver fibrosis, when liver fibrosis had been induced by long-term treatment with carbon tetrachloride (CCl4). Thus, the administration of HGF holds great promise for treating subjects with liver fibrosis/cirrhosis as a result of chronic hepatic injury.

Alanine Transaminase↗
PubMed1997

Possibility of defense against colorectal tumor by foamy cells.

To investigate the difference between colorectal adenocarcinomas with white spots (foamy cells) and those without white spots, clinically and histopathologically, we examined 112 cases of colorectal adenocarcinomas in this study. Thirty-two cases were diagnosed as submucosal invasive adenocarcinoma and 80 as advanced adenocarcinoma. They were classified into two groups: with white spots and without white spots. Submucosal tumors and squamous epithelial-origin tumors were excluded. In each case we looked for evidence of lymph node and liver metastases. Immunoreactive staining for macrophages, foamy cells, T cells, and B cells was also performed. We found a significant difference in the incidence of lymph node metastasis between the two groups with advanced carcinoma. White spots (foamy cells) were present at some distance from carcinoma cells. We conclude that foamy cells might have a beneficial role. From a histopathological viewpoint they can be considered a possible physical defense wall, an index of immune response activation. Clinically, it is important not to overlook any lesion.

Adenocarcinoma↗
PubMed1997

Coagulative and fibrinolytic activation in cerebrospinal fluid and plasma after subarachnoid hemorrhage.

OBJECTIVE: Intrathecal fibrinolytic therapy has been used as one of the anticerebral vasospasm (VS) preventative therapies in patients with subarachnoid hemorrhage (SAH). However, the changes in coagulation and fibrinolysis in the blood and cerebrospinal fluid (CSF) after SAH remain unknown. METHODS: Fifty patients with SAH caused by ruptured cerebral aneurysms were studied postoperatively to detect the serial changes of the thrombin-antithrombin III complex, active plasminogen activator inhibitor (PAI)-1, and tissue plasminogen activator (tPA)-PAI complex (tPA-PAI) activities in the plasma and CSF collected from cisternal drainage catheters. RESULTS: The CSF levels of all parameters and plasma PAI-1 levels were significantly higher in patients with severe SAH than in those with mild SAH. There was no relationship between the CSF and plasma levels of these parameters (except the CSF levels of tPA-PAI) and the initial neurological statuses. The CSF PAI-1 levels increased to greater than 20 ng/ml near the time of the occurrence of cerebral VS, whereas they remained below 20 ng/ml in patients without VS. The CSF tPA-PAI levels showed the highest peak near the time of VS remission. The CSF PAI-1 and tPA-PAI levels were significantly lower in patients with good outcomes than in those with poor outcomes. CONCLUSION: Both the coagulative and fibrinolytic systems were activated in the CSF and plasma after SAH in correlating to the amount of SAH clot. The intrathecal administration of fibrinolytic agents should be started early after surgery, before CSF PAI-1 levels increase, for patients with severe SAH. Patients with CSF PAI-1 levels greater than 20 ng/ml experienced high incidence of VS and poor outcomes.

Adult↗
PubMed1997

Selective depletion of neutrophils by a monoclonal antibody, RP-3, suppresses dextran sulphate sodium-induced colitis in rats.

Administration of dextran sulphate sodium to animals induces acute colitis characterized by infiltration of large numbers of neutrophils into the colonic mucosa, which histologically resembles human active ulcerative colitis. It has been reported that neutrophils and the reactive oxygen metabolites produced by them are involved in the progress of ulcerative colitis. This study was intended to clarify their roles by using this animal model. First, possible sources and species of reactive oxygen metabolites were determined using luminol-dependent chemiluminescence with addition of enzyme inhibitors and reactive oxygen metabolite scavengers. Next, to examine whether neutrophils and hypochlorous acid derived from them contribute to tissue injury, we administered RP-3, a monoclonal antibody capable of selectively depleting neutrophils, and taurine, a hypochlorous acid scavenger, to rats treated with dextran sulphate sodium. Addition of azide, taurine, catalase, superoxide dismutase and dimethyl sulphoxide into colonic mucosal scrapings significantly inhibited chemiluminescence production, but allopurinol and indomethacin had no effects. These results suggest that excessive hypochlorous acid, hydrogen peroxide, superoxide anion and hydroxyl radical are generated by the inflamed colonic mucosa. Intraperitoneal injections of RP-3 significantly suppressed bleeding, tissue myeloperoxidase activity, chemiluminescence production and erosion formation. On the other hand, administration of taurine tended to inhibit bleeding and erosion formation to some extent, although it could not significantly suppress them. These data suggest that neutrophils play an important role in the development of this colitis and that hypochlorous acid might be one of the causes of tissue injury induced by neutrophils.

Animals↗
PubMed1997

Risk factors and the effect of interferon therapy in the development of hepatocellular carcinoma: a multivariate analysis in 343 patients.

The aims of the present study were to clarify the risk factors for the development of hepatocellular carcinoma (HCC) in chronic hepatitis C virus (HCV) infection and to investigate the effectiveness of interferon (IFN) therapy. We retrospectively studied 343 patients who had been admitted to our hospital; 161 with chronic hepatitis, 49 with liver cirrhosis, 42 with chronic hepatitis bearing HCC and 91 with liver cirrhosis bearing HCC. The mean (+/- SD) observation period was 41.6 +/- 31.1 months. The mean age of HCC and non-HCC patients was 63.5 +/- 7.6 and 56.9 +/- 12.5 years, respectively (P < 0.001). The HCV genotype II (1b) was the most prevalent genotype (92.5%) in HCC patients and the mean age was higher among patients with this genotype (63.6 +/- 7.7 years). Multivariate analysis identified age (P < 0.001), the male gender (P < 0.01), HCV genotype II (1b) (P < 0.05) and excessive alcohol intake (P < 0.05) as independent factors associated with the development of HCC. There was no relationship between the development of HCC and serum HCV levels as quantified by branched DNA assay or competitive reverse transcription polymerase chain reaction. The incidence of HCC in patients who had not received IFN therapy was 10.4/100 person-year, while that of patients who had received IFN therapy was 1.2/100 person-year (P < 0.01) by the person-year method. The low incidence of HCC in patients treated with IFN suggests that IFN may prevent the development of HCC.

Aged↗
PubMed1997

Metallothionein expression and concentrations of copper and zinc are associated with tumor differentiation in hepatocellular carcinoma.

Metallothionein is the carrier protein of heavy metal ions, such as copper (Cu) and zinc (Zn). In this study, the relationships among immunohistochemical expression of metallothionein, concentrations of Cu and Zn, histological differentiation and proliferative activity of hepatocellular carcinoma were investigated in 51 cases. The concentrations of Cu and Zn in both tumor and non-tumor tissues were determined using electron probe microanalysis. Immunohistochemical expression of metallothionein in tumor tissues decreased with the degree of differentiation, whereas the number of hepatocytes positive for Ki-67 increased. Furthermore, the concentrations of Cu and Zn in tumor tissues decreased with the degree of histological differentiation in human hepatocellular carcinoma.

Biomarkers, Tumor↗
PubMed1997

[Enterohemorrhagic Escherichia coli O157 outbreak in Obihiro-city--biological and molecular characteristics among O157 isolates].

The outbreak of enterohaemorrhagic Escherichia coli (EHEC) O157:H7 infection in Obihiro City, Japan, occurred in late October 1996. The infection affected a total of 169 kindergarten pupils and school staff members in a private kindergarten. Twenty-one children (12.4%) progressed into hemolytic uremic syndrome (HUS). Moreover, the person-to-person infections in 9 families and the duration of excretion of EHEC in 13 patients were observed. The contaminated food was identified as the potato-salad served at lunch. Analysis of biological characteristics, the ability of toxin production, and the DNA analysis by PCR-based fingerprinting, the RAPD tests, among all clinical isolates, clarified a homologous origin of contamination.

Adult↗
PubMed1997

Induction of intestinal lesions in nu/nu mice induced by transfer of lymphocytes from syngeneic mice infected with murine retrovirus.

BACKGROUND: Murine leukemia virus, LP-BM5, induces severe immunodeficiency with abnormal lymphoproliferation in susceptible C57BL/6 mice. In a previous study, it was shown that a Sjögren's syndrome-like systemic exocrinopathy is induced in the virus infected mice. AIMS: To examine lymphocyte functions of the virus infected mice. METHODS: Four-week old mice were inoculated with the virus and their spleen cells were transferred into syngeneic nu/nu mice. Their organs were examined by light and electron microscopy. Phenotypes of the colon infiltrating cells were examined by flow cytometry. RESULTS: All nu/nu recipients had died by six weeks after cell transfer, showing runting disease like cachexia with diarrhoea and anal bleeding. Histopathological examination revealed that systemic exocrinopathy was adoptively transferable and that the colon became thickened due to mononuclear cell infiltration into the mucosal and submucosal layer with hyperplasia of intestinal epithelial cells. No virus particles were found in the colon. Flow cytometric analyses revealed that most of the infiltrating CD4+ T cells showed CD45RBlow. No intestinal lesions were observed in the virus infected mice nor in nu/nu mice inoculated with normal lymphocytes. CONCLUSION: Lymphocytes of the virus infected mice induced colitis and hyperplasia of intestinal epithelial cells as well as systemic exocrinopathy in nu/nu mice. Our experimental system may give some insight into intestinal lesions associated with virus infection.

Animals↗
PubMed1997

Expression of genes encoding corticotropin-releasing factor (CRF), type 1 CRF receptor, and CRF-binding protein and localization of the gene products in the human ovary.

Recently, the presence of immunoreactive corticotropin-releasing factor (IrCRF) in the thecal-stromal cells of the human ovary and the ability of CRF to suppress estrogen production by human granulosa cells in vitro have been reported. To understand the functional role of ovarian CRF requires characterization of the human ovarian CRF system, which includes CRF, type 1 CRF receptor (CRF-R1), and the high affinity CRF-binding protein (CRF-BP). Accordingly, we have examined the ovarian CRF system and the cellular distribution of these proteins and their messenger ribonucleic acids (mRNAs) using immunohistochemistry and in situ hybridization, respectively. Normal ovaries from 10 premenopausal women undergoing hysterectomy with ovariectomy were used in the analyses. IrCRF and its mRNA were localized in thecal cells of small antral and mature follicles. A low abundance of IrCRF and mRNA was also detected in stromal cells of both stages of follicles. Expression of the gene encoding CRF was more prominent in mature follicles than in small antral follicles. CRF-R1 mRNA signal was found exclusively in thecal cells of mature follicles and moderately in small antral follicles. Granulosa cells were devoid of CRF and CRF-R1 mRNAs and proteins. The IrCRF-BP, but not its transcript, was detected in thecal cells and luman of capillary vessels of the thecal/stromal compartment of mature follicles. The absence of CRF-BP gene transcript in human ovarian follicles was confirmed by reverse transcription-PCR, indicating that the IrCRF-BP detected is not derived from the ovarian transcript and suggesting that the presence of IrCRF-BP and luman of capillary vessels in the thecal compartment originates from the peripheral circulation. Thecal cells of mature follicles, relative to those of small antral follicles, exhibited an intensive immunostaining and mRNA signal for 17 alpha-hydroxylase (P450c17) indicative of androgen biosynthesis. We conclude that the thecal compartment of the human ovary contains a CRF system endowed with CRF and CRF-R1 and the blood-derived CRF-BP. Granulosa cells are devoid of the CRF system. The parallel increases in intensity of CRF, CRF-R1, and 17 alpha-hydroxylase proteins and gene expression with follicular maturation suggest that the intraovarian CRF system may play an autocrine role in androgen biosynthesis with a downstream effect on estrogen production by the granulosa cells. The functionality of the ovarian CRF system may be conditioned by the relative presence of circulating CRF-BP by virtue of its ability to compete with CRF for the CRF receptor.

Adult↗
PubMed1997

Effects of maternal infection on prostaglandin production and uterine contraction in late-gestation pregnant goats.

The main objective of this study was to evaluate the relationship between maternal infection induced by pyrogen administration and the changes in maternal and fetal plasma levels of prostaglandin E2 (PGE2) and F 2 alpha (PGF 2 alpha) and uterine contraction. We administered one mg of pyrogen (E. coli endotoxin) into the maternal femoral vein; then then the changes in maternal and fetal core temperatures, plasma levels of PGE2, [PGE2] and PGF 2 alpha, [PGF 2 alpha]. pO2, pCO2, pH and maternal uterine contractions were measured in late-gestation pregnant goats (n = 8). Maternal and fetal core temperatures were elevated significantly 30 min after pyrogen administration (p < 0.05), reached their peak levels after 3 hours, and after 5 hours mean core temperatures returned to levels indistinguishable from initial control. Maternal plasma [PGE2] and [PGF 2 alpha] increased to 4318 +/- 321 pg/ml after 1 hour and to 670.8 +/- 58.4 pg/ml after 3 hours respectively (p < 0.05). Fetal plasma [PGF 2 alpha] increased significantly (p < 0.05) to 811.0 +/- 64.0 pg/ml after 1 hour; however, plasma [PGE2] did not change throughout the study. Periodic uterine contractions appeared after 3 hours and disappeared after 5 hours. These results suggest that pyrogen induces the elevation of maternal and fetal core temperatures and prostaglandin production, and that eventually causes uterine contractions.

Animals↗
PubMed1997

Thermographic demonstration of nonshivering thermogenesis in human newborns after birth: its relation to umbilical gases.

This study was undertaken to measure the extent of nonshivering thermogensis (NST) in brown adipose tissue of human newborns receiving routine thermal care and to examine the influence of oxygen levels at birth on the initiation of NST. Fifteen human neonates were studied in an incubator set at 31-31 degrees C. Thermographic measurements were made every 5 seconds for 5 minutes at 10 and 30 minutes, 1, 3, 6 and 24 hours, and 3 days after birth. The skin temperature and rate of heat dissipation from the interscapular area (location of subcutaneous brown adipose tissue), whole back area, and head area were measured. A heat dissipation ratio (HDR) was calculated as (A-B)/B, where A and B, expressed in Cal/cm2/h, represent rates of heat dissipation from the interscapular area and the whole back area, respectively. Umbilical arterial blood gases were measured immediately after birth. The skin temperature of the interscapular, whole back, and head areas increased significantly during the interval from 10 minutes to 1 hour after birth (p < 0.05). The skin temperature of the interscapular area was highest among the sampled sites during the first hour after birth (p < 0.05). The HDR was highest 10 minutes after birth (p < 0.05). By 1 hour after birth the temperature had reached constant values with low HDR. There was a negative correlation between the HDR and the temperature of the whole back area (p < 0.001). A positive correlation was found between the HDR within 30 minutes after birth and the PO2 of the umbilical arterial blood (p < 0.001). The data support the conclusion that nonshivering thermogenesis is initiated within minutes of birth and contributes to the elevation of body temperature. Furthermore, nonshivering thermogenesis after birth is reduced by low arterial PO2 at the time of birth.

Adult↗