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Biomedical subjects

A Ito

Publications and source records attributed to A Ito.

At least 271 records · Page 15Linked to original sources

Contrast-enhanced endoscopic ultrasonography in gallbladder diseases.

BACKGROUND: The purpose of this study was to investigate the usefulness of contrast-enhanced endoscopic ultrasonography in gallbladder diseases. METHODS: Subjects were 38 patients including 12 with adenocarcinoma, 2 adenosquamous carcinoma, 6 cholesterol polyp, 10 cholecystitis, and 8 adenomyomatosis. After endoscopic ultrasonography, sonicated albumin was intravenously injected and the enhanced effect on images of these lesions was determined. For malignancies we compared diagnostic accuracy (T factor, TNM classification) of endoscopic ultrasonography and contrast-enhanced endoscopic ultrasonography. Vascularity as shown by contrast-enhanced endoscopic ultrasonography and angiograms was compared. RESULTS: Enhancement was observed in 11 patients with adenocarcinoma but not of those with adenosquamous carcinoma or cholesterol polyp. Angiography provided hypervascular images for all cases of adenocarcinoma, but all other lesions were hypovascular. In one case of adenocarcinoma, 3 cases of adenomyomatosis, and 8 cases of cholecystitis, there was a discrepancy between contrast-enhanced endoscopic ultrasonography images and angiograms with regard to vascularity. The accuracy of depth of tumor invasion for endoscopic ultrasonography was 78.6% (11 of 14) versus 92.9% (13 of 14) for contrast-enhanced endoscopic ultrasonography. CONCLUSION: Contrast-enhanced endoscopic ultrasonography is useful in the diagnosis of gallbladder lesions.

Adenocarcinoma↗

Human urinary trypsin inhibitor inhibits the activation of pro-matrix metalloproteinases and proteoglycans release in rabbit articular cartilage.

Treatment of primary cultured chondrocytes from rabbit articular cartilage with interleukin-1 (IL-1)alpha and plasminogen induced the production of pro-matrix metalloproteinase 1 (proMMP-1/interstitial collagenase), proMMP-3 (stromelysin 1) and proMMP-9 (gelatinase B), as well as their active forms. Human urinary trypsin inhibitor (UTI), a multipotent inhibitor of serine proteases, including plasmin inhibited the activation of proMMP-1, proMMP-3 and proMMP-9 when added to the culture medium together with IL-1alpha and plasminogen, in a dose-dependent manner. Moreover, UTI inhibited the release of proteoglycans induced by IL-1alpha and plasminogen from rabbit articular cartilage explants. These findings strongly suggest that UTI inhibits the destruction of articular cartilage induced by plasmin and/or MMPs. Thus, UTI probably exert an anti-osteoarthritic action via inactivation of proMMPs.

Animals↗

Ovariectomy-induced hyperalgesia and antinociceptive effect of elcatonin, a synthetic eel calcitonin.

Using ovariectomized (OVX) rats in the tail-withdrawal nociceptive test, we examined OVX-induced hyperalgesia and the antinociceptive effect of subcutaneously administered elcatonin, a synthetic derivative of eel calcitonin ([Asu1.7] eel calcitonin). Because tail-withdrawal latency was significantly and continuously reduced and bone mineral density decreased in OVX rats compared with those of sham-operated rats, it was demonstrated that ovariectomy induced prolonged hyperalgesia and osteoporosis. After repeated administrations for 3 or 4 weeks, subcutaneously injected elcatonin increased the latency of the OVX rats in a dose-dependent manner, compared to the vehicle-treated OVX rats. At a dose of 20 U/kg/day, there were significant differences (p < 0.01) in the latency between the elcatonin- and vehicle-treated OVX rats. This effect of elcatonin was completely inhibited by p-chlorophenylalanine treatment, suggesting that the central serotonergic system may be involved in the elcatonin antinociception of OVX-induced hyperalgesia.

Analgesics↗

Induction of thyroid tumours in (C57BL/6N x C3H/N)F1 mice by oral administration of kojic acid.

The tumorigenicity of kojic acid (KA), which is widely used for food and cosmetics in Japan, was examined in B6C3F1 mice. Female and male animals were divided into three groups and given 0, 1.5 and 3.0% KA containing food from the age of 6 weeks. At sacrifice after 20 months, thyroid weights were significantly increased in both sexes of mice receiving KA, especially in the male groups. The enlarged thyroid glands histologically featured diffuse hyperplasia and follicular adenomas, the incidences of the latter being 65% and 87%, respectively in 1.5% and 3.0% KA-treated males, significantly higher than the control value of 2%. In the females, the figures were 2%, 8% and 80% in the 0%, 1.5% and 3.0% KA groups, respectively. The serum free T3 levels in the 3.0% KA animals of both sexes at month 6 were significantly lower than in the controls. On the other hand, their serum TSH levels were higher, although the differences disappeared at later time points. In conclusion, continuous administration of high dose of KA induces thyroid adenomas in male and female B6C3F, mice, presumably by a mechanism involving decrease in serum free T3 levels and increased TSH.

Adenoma↗

Inhibitory effect of amphotericin B on leukotriene B4 synthesis in human neutrophils in vitro.

Our objective was to determine the effect of amphotericin B on leukotriene (LT) A4 hydrolase in human neutrophil cytosol and to examine its effect on intact neutrophils in vitro. Cytosolic fractions were assayed for LTA4 hydrolase and 5-lipoxygenase activity in the presence or absence of amphotericin B. The IC50 of amphotericin B for LTA4 hydrolase activity was 0.72 microM. No inhibition of 5-lipoxygenase activity in the cytosolic fraction was detected. The IC50 of amphotericin B for leukotriene B4 synthesis in intact neutrophils was 0.43 microM. The 5-hydro(per) oxy-eicosatetraenoic acid (5-H(P)ETE) synthesis was diminished in intact cells by 66.8 [3.4]% (mean[SEM]) in the presence of 0.01 mM amphotericin B. Thus, amphotericin B inhibited the synthesis of LTB4 and 5-H(P)ETE in neutrophils in vitro. Differences between the results of studies on cytosol and on intact cells suggest that amphotericin B is involved in a complex interaction in the intact cell.

Amphotericin B↗

Experimental infection of larval Echinococcus multilocularis in the rodent brain as a model for cerebral alveolar echinococcosis.

Experimental infection of larval Echinococcus multilocularis in the rodent brain was attempted to establish a murine model for cerebral alveolar echinococcosis. Balb/c mice and jirds were injected intracranially with 10% of a homogenated hydatid cyst mass. Small cystic larvae were observed macroscopically in the cranial cavity 1, 2 and 5 months post-infection in both mice and jirds. Some larval cysts from both rodents contained mature or immature protoscoleces. In mice, the laminated layer was found in the lateral ventricle 2 months post-infection but without protoscoleces. At five months post-infection, larger larval cysts were found in the cranial cavity of a mouse, which also demonstrated partial palsy of the legs. A laminated layer with mature protoscoleces was observed in the third ventricle and the mouse also harboured, in the left lung, a larval cyst containing protoscoleces surrounded by lymphocytes. Jirds were also found to be infected with metacestodes in the cranial cavity, but neither unusual behaviour nor establishment of cysts inside the brain was observed in jirds during the course of infection.

Animals↗

Eosinophil chemotactic factors from cysticercoids of Hymenolepis nana.

A comparative study of eosinophil chemotactic factors was carried out using cysticercoids and oncospheres of Hymenolepis nana. Cysticercoids showed twice the chemotactic activity for eosinophils than the oncospheres. Eosinophilia induced by oncospheres and cysticercoids observed in secondary and primary infections, respectively, were discussed from the view point of the immunobiology of this parasite.

Animals↗

Pemphigus with features of both vulgaris and foliaceus variants, associated with antibodies to 160 and 130 kDa antigens.

We report an unusual variant of pemphigus in a 44-year-old man. He presented with scaly and crusted erosions associated with pruritic vesicles and erythema mainly on the chest, abdomen, back and face. Histology showed acantholysis with neutrophilic spongiosis in the granular layer and subcorneal region of the epidermis. Intercellular IgG in the epidermis was positive on direct immunofluorescence. Indirect immunofluorescence showed intercellular antibodies at a titre of 1 : 2 in the suprabasal epidermis. Circulating autoantibodies to 130 kDa and 160 kDa antigens were detected in the patient's serum by immunoblot analysis using epidermal extracts. These two antibodies eluted from individual nitrocellulose membranes reacted with the intercellular space in the epidermis on indirect immunofluorescence. This observation suggests that these antibodies correspond to desmogleins 3 and 1, respectively. The clinical symptoms almost completely disappeared after 28 days treatment with oral prednisolone (30 mg/day), leaving brown pigmented flecks on the lesional sites. These findings suggest that this patient's pemphigus has features of both the vulgaris and foliaceus variants, with antibodies against desmogleins 3 and 1.

Adult↗

Cross-linking of Fc(gamma)-receptor on monocytes inhibits hepatitis C virus-specific cytotoxic T-lymphocyte induction in vitro.

In hepatitis C virus (HCV) infection, immune complex (IC)-type virus particles are frequently observed in circulation. The IC leads to cross-linking of Fcgamma receptors (FcgammaR) on monocytes and exerts immunoinhibitory function. To test the roles of IC in HCV-specific cytotoxic T lymphocyte (CTL) induction, we generated HCV CTL from peripheral blood mononuclear cells of chronic hepatitis C patients with or without HCV-IC- or immunoglobulin G (IgG)-coated culture plates and compared their lytic activities. HCV-IC or adherent IgG, which induces FcgammaR cross-linking, significantly reduced CTL activity. Expression of B7-1 on monocytes decreased on adherent IgG. In addition, tumour necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta1 (TGF-beta1) production increased from cells on adherent IgG and their mRNA expression in monocytes was enhanced. Anti-TNF-alpha antibody during induction on adherent IgG inhibited lysis; however, anti-TGF-beta completely reversed its inhibitory effect. These results demonstrated that HCV-IC or adherent IgG impaired HCV-CTL induction in vitro. The FcgammaR-mediated CTL suppression occurred via decreased expression of monocyte B7-1 and/or enhanced production of TGF-beta1.

Adult↗

Ultrasonographic and serologic studies of experimental cysticercosis in rats infected with Taenia taeniaeformis.

Rats experimentally infected with Taenia taeniaeformis were followed-up until 14 weeks post inoculation with eggs (PIE) by hepatic ultrasonographic (US) image and serum antibody response analyses. Parasitic cysts could be imaged as small (2 mm in diameter) anechoic areas with or without a parenthesis-like echogenic small line from two weeks PIE. Immunoblot analysis using antigens from oncospheres (TtO), 30-day-old (TtM-30) and 300-day-old metacestodes (TtM-300) revealed that: (1) these three different developmental stages showed their own unique patterns suggesting the presence of stage-specific antigens; (2) faint IgM antibody responses to some components of TtO and TtM-30 or TtM-300 could be detected from one and two weeks PIE, respectively, and (3) IgG responses to some major components of both TtO and TtM-300, and TtM-30 were easily detected from four and five weeks PIE onwards, respectively. Both TtO and TtM (especially TtM-300) appeared to be highly useful for detection of antibody responses in experimentally infected rats. Due to the easiness in preparation of antigens, fully developed metacestodes may be the best candidate antigens for serodiagnosis. These results strongly suggest that both US image and antibody analyses using antigens from fully developed metacestodes are useful for detection of the early stage of cysticercosis in laboratory animal model.

Animals↗

Immunoblot analysis of a 10 kDa antigen in cyst fluid of Taenia solium metacestodes.

The diagnostic value of a 10 kDa subunit of 150 kDa protein in cyst fluid (CF) of Taenia solium metacestodes was evaluated. Immunoblot analysis revealed that most sera from patients with neurocysticercosis recognized the 10 kDa subunit strongly (209/217 cases, 84.6%), while a few sera from individuals with other parasitic diseases including alveolar echinococcosis (AE, 2/20, 10%) and cystic echinococcosis (CE, 2/25, 8%) showed faint reactions. Sera of cases with other parasitic diseases, especially AE and CE, exhibited cross reactions against other bands in CF. Both differential immunoblot and immunoprecipitation analyses showed that the 10 kDa subunit was the most specific to cysticercosis and highly antigenic, whereas other components at 20-40, 64, 95 and 106 kDa in CF were cross-reactive. IgG subclass ELISA and immunoblot demonstrated that both IgG4 and IgG1 reactions were predominant in neurocysticercosis and recognized the 10 kDa.

Animals↗

Effects of miso and NaCl on the development of colonic aberrant crypt foci induced by azoxymethane in F344 rats.

The present study was designed to investigate the effects of dietary miso and NaCl supplementation on the development of aberrant crypt foci (ACF) induced by azoxymethane (AOM) in male F344 rats. A total of 76 rats, six weeks of age, were divided into seven groups and given weekly subcutaneous injections of AOM (15 mg/kg body wt) for three weeks to induce ACF. The animals were placed on diets one week before the first AOM dosing. Group 1 was fed a normal diet as a control. Groups 2-4 were fed diets containing 5%, 10%, and 20% miso, respectively, and Groups 5 and 6 were fed diets containing 2.2% and 4.4% NaCl, respectively, for five weeks. Group 7 was fed a normal diet without carcinogen exposure. Dietary miso inhibited the development of ACF in a dose-dependent manner (y = -3.9x + 140, r = -0.94). Thus the mean numbers of ACF per colon were significantly lower in Groups 3 and 4 than in Group 1 (p < 0.01), and there were fewer aberrant crypts per colon in Group 4 than in Group 1. NaCl supplementation was associated with fewer ACF, but this was not statistically significant. 5-Bromo-2'-deoxyuridine labeling indexes in the colonic epithelium were significantly lower in Group 3 than in Group 1 (p < 0.05). The present results indicate that dietary miso could act as a chemopreventive agent for colon carcinogenesis.

Animals↗

Characterization of the initial steps of precursor import into rat liver mitoplasts.

Mitochondria have two independent protein-import machineries, one in the outer membrane (the Tom system) and the other in the inner membrane (the Tim system). Here, we have characterized the initial steps of precursor import into rat liver mitoplasts. The import reaction was separated into two stages, consisting of precursor binding to the mitoplasts at 0-10 degreesC, and a subsequent chase reaction at 30 degreesC. This assay revealed four distinct precursor-import steps: DeltaPsi-dependent initial binding of the precursor, precursor transfer to the Tim23-Tim17 stage, DeltaPsi-dependent translocation of the presequence across the inner membrane, and the complete translocation of the mature portion of the precursor. Antibodies against the intermembrane space domain of Tim23 inhibited neither the precursor binding nor the subsequent translocation of the presequence across the inner membrane. In contrast, the antibodies inhibited the complete translocation of the mature domain of the precursor across the inner membrane. Immunoprecipitation with anti-Tim23 IgGs revealed that the precursor-Tim23 complex increased with time and temperature after the initial targeting of the precursor to the mitoplasts. These results suggest that the precursor is first targeted to the inner membrane component DeltaPsi-dependently, then transferred to the Tim system consisting of Tim23-Tim17, and finally imported into the matrix.

Amino Acid Sequence↗

Importance of residues carboxyl terminal relative to the cleavage site in substrates of mitochondrial processing peptidase for their specific recognition and cleavage.

We previously identified distal and proximal arginine residues in the N-terminal portion and an aromatic amino acid at position 1 (P1' site3) relative to the cleavage site as important recognition signals in substrates of mitochondrial processing peptidase [Niidome, T., Kitada, S., Shimokata, K., Ogishima, T., and Ito, A. (1994) J. Biol. Chem. 269, 24714-24722; Ogishima, T., Niidome, T., Shimokata, K., Kitada, S., and Ito, A. (1995) ibid. 270, 30322-30326]. To further elucidate the elements required for the specific recognition and cleavage by the enzyme, we synthesized synthetic peptides that possessed only the distal and proximal arginine residues and phenylalanine at the P1' site in a poly alanine sequence, and analyzed the processing reaction toward them. They were not cleaved by the peptidase although they inhibited the peptidase activity. However, when serine was introduced into the C-terminal portions of the sequence, processing was observed. The efficiency of the resultant peptides improved as the number of serine residues was increased. A peptide with serine or histidine at P2' and threonine at P3' was processed most efficiently. These results indicate that the processing reaction catalyzed by the peptidase depends not only on the N-terminal portion but also on the C-terminal portion from the cleavage site in the substrates.

Amino Acid Sequence↗

Chemoprevention of N-nitroso-N-methylurea-induced rat mammary carcinogenesis by soy foods or biochanin A.

We examined the effects of soybeans, a soy product (miso) and biochanin A, an isoflavone derivative, on N-nitroso-N-methylurea (MNU)-induced rat mammary carcinogenesis. Seven-week-old female CD/Crj rats received a single i.v. dose (40 mg/kg body weight) of MNU. After administration of MNU, rats were fed diet containing 0% (control), 2% or 10% soybeans, or 10% miso as a soy-supplemented diet, or 10 or 50 mg/kg biochanin A. All rats were observed for 18 weeks after MNU administration. At 18 weeks, the multiplicity (mean tumors/rat) of palpable mammary tumors was significantly decreased in the 10% soybean (1.1) and 10% miso (1.2) diet groups compared to the control (2.2) (P<0.05, respectively). In the biochanin A-supplemented diet groups, the incidence (percentage of rats with tumors) was significantly decreased in the 50 mg/kg (32%) diet group compared to the control (80%) (P<0.01), and the multiplicity was significantly decreased in both the 10 mg/kg (0.7) and 50 mg/kg (0.5) diet groups compared to the control (2.2) (P<0.01 and P<0.001, respectively). The proliferative cell nuclear antigen labeling index of mammary tumors was significantly decreased in both biochanin A-supplemented diet groups compared to the control. The present results indicate that soybeans, miso, and biochanin A are useful for the prevention of mammary cancer.

Animals↗

Chemoprevention of N-nitroso-N-methylurea-induced rat mammary cancer by miso and tamoxifen, alone and in combination.

We examined the effects of a Japanese fermented soybean product, miso, and tamoxifen (TAM), alone and in combination, on N-nitroso-N-methylurea (MNU)-induced rat mammary cancer. Seven-week-old female CD/Crj rats received a single i.v. dose (50 mg/kg body weight) of MNU. After administration of MNU, the rats were divided into 4 groups: regular diet (control), 10% miso diet, regular diet + TAM, and 10% miso diet + TAM. TAM was implanted s.c. in the form of pellets containing 2.5 mg at the same time as MNU was administered. All rats were observed for 18 weeks after MNU administration. Incidence (percentage of rats with tumors) and multiplicity (mean tumors/rat) of mammary tumors were 91% and 4.5 in the control, 77% and 2.4 (P < 0.05) in the 10% miso group, 68% and 1.4 (P <0.01) in the TAM group, and 10% (P < 0.0001 or less) and 0.2 (P < 0.0001) in the 10% miso + TAM group. In the second experiment, the effect of the combination of miso and TAM on established rat mammary tumors was investigated. When the mammary tumors induced by MNU reached 10 to 25 mm, the rats were divided into 3 treatment groups: regular diet, regular diet + TAM, and 10% miso diet + TAM. At 6 weeks after the start of treatment, the mean tumor size in the control and TAM groups was 160% and 141% of the pretreatment value, but a decrease of 85% of the pretreatment value was produced by the combination of miso and TAM, and this was significantly different from both the control and TAM groups (P < 0.01) and P < 0.05, respectively). These results indicate that miso is useful in protecting against mammary cancer and it can be expected to have a potent antitumor effect, especially when used in combination with TAM.

Animals↗

Contrast-enhanced endoscopic ultrasonography in pancreatic diseases: a preliminary study.

OBJECTIVE: The purpose of this study was to clarify the usefulness of contrast-enhanced endoscopic ultrasonography in pancreatic diseases. METHODS: The subjects comprised 37 patients with pancreatic diseases: 11 with ductal cell carcinoma, 10 with mucin-producing tumor, five with pseudo-cyst, four with islet cell tumor, four with chronic pancreatitis, and three with serous cystadenoma. After endoscopic ultrasonography, Albunex (0.22 ml/kg) was injected intravenously at a rate of 1 ml/s into the right median vein, and observation was continued for 10 min. The presence or absence of enhancement of the lesion was determined in each disease. Because all the patients with ductal cell carcinoma, islet cell tumor, chronic pancreatitis, and serous cystadenoma, as well as five with mucin-producing tumor and three with pseudo-cyst, underwent angiography, vascularity was compared between angiographic images and those of contrast-enhanced ultrasonography. RESULTS: Enhancement of the lesion was observed in all patients with islet cell tumor and serous cystadenoma, in eight with mucin-producing tumor, and in three with chronic pancreatitis. However, no enhancement effect was observed in the patients with ductal cell carcinoma and those with pseudo-cyst. Comparison between the images of contrast-enhanced endoscopic ultrasonography and angiographic images showed three patients in whom angiograms were hypovascular, but enhancement effect was observed on ultrasonographic images. CONCLUSION: The combined evaluation of plain and enhanced images of endoscopic ultrasonography may be useful for the diagnosis of pancreatic diseases.

Adenocarcinoma, Mucinous↗

In vitro cytotoxic effects of vacuolating cytotoxin produced by clinical isolates of Helicobacter pylori.

The vacuolating cytotoxin produced by Helicobacter pylori is considered to be one virulence factor causing peptic ulceration. In this study, we examined the activity of vacuolating cytotoxin in induction of intracellular vacuolation of rabbit gastric epithelial cells (RGECs). We used culture supernatants of H. pylori as a source of vacuolating cytotoxin and quantitated cytotoxic activity by the MTT method. Intracellular vacuolation of RGECs was observed in the presence of 36 of 57 (63%) clinically isolated H. pylori strains. However, there were no differences in the incidence of H. pylori strains with positive vacuolating cytotoxin (Tox+) among patients with gastritis, gastric ulcers or duodenal ulcers. The MTT assay showed that the cytotoxic activity of H. pylori supernatants obtained from patients with gastric ulcers was significantly higher than in patients with gastritis (p < 0.01), but was not different to duodenal ulcer patient supernatants. Similar results were also observed in Tox+ isolates, however, there were no significant differences between patients with regard to the incidence of vacuolating cytotoxin-negative isolates. Although our data may not indicate a clear correlation between prevalence of vacuolating cytotoxin and clinical manifestations, they suggest that H. pylori harboring vacuolating cytotoxin may particularly induce damage to the gastric epithelium in patients with gastric ulcers.

Animals↗