Infliximab as a treatment for systemic amyloidosis associated with Crohn's disease.
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Adult↗
Biomedical subjects
Y Horie
Publications and source records attributed to Y Horie.
Efficacy of ecabet sodium enema on steroid resistant or steroid dependent ulcerative colitis.
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Abietanes↗
Tumour necrosis factor alpha signalling through activation of Kupffer cells plays an essential role in liver fibrosis of non-alcoholic steatohepatitis in mice.
BACKGROUND: While tumour necrosis factor alpha (TNF-alpha) appears to be associated with the development of non-alcoholic steatohepatitis (NASH), its precise role in the pathogenesis of NASH is not well understood. METHODS: Male mice deficient in both TNF receptors 1 (TNFR1) and 2 (TNFR2) (TNFRDKO mice) and wild-type mice were fed a methionine and choline deficient (MCD) diet or a control diet for eight weeks, maintaining isoenergetic intake. RESULTS: MCD dietary feeding of TNFRDKO mice for eight weeks resulted in attenuated liver steatosis and fibrosis compared with control wild-type mice. In the liver, the number of activated hepatic Kupffer cells recruited was significantly decreased in TNFRDKO mice after MCD dietary feeding. In addition, hepatic induction of TNF-alpha, vascular cell adhesion molecule 1, and intracellular adhesion molecule 1 was significantly suppressed in TNFRDKO mice. While in control animals MCD dietary feeding dramatically increased mRNA expression of tissue inhibitor of metalloproteinase 1 (TIMP-1) in both whole liver and hepatic stellate cells, concomitant with enhanced activation of hepatic stellate cells, both factors were significantly lower in TNFRDKO mice. In primary cultures, TNF-alpha administration enhanced TIMP-1 mRNA expression in activated hepatic stellate cells and suppressed apoptotic induction in activated hepatic stellate cells. Inhibition of TNF induced TIMP-1 upregulation by TIMP-1 specific siRNA reversed the apoptotic suppression seen in hepatic stellate cells. CONCLUSIONS: Enhancement of the TNF-alpha/TNFR mediated signalling pathway via activation of Kupffer cells in an autocrine or paracrine manner may be critically involved in the pathogenesis of liver fibrosis in this NASH animal model.
Animals↗
Elemental diet modulates the growth of Clostridium difficile in the gut flora.
BACKGROUND AND AIMS: Tube feeding is regarded as a risk factor for Clostridium difficile-associated diarrhoea. Recently, we reported that C. difficile toxin was frequently found in patients receiving an elemental diet. The present study was conducted to clarify whether elemental diets are associated with the growth of C. difficile in the gut flora. METHODS: C. difficile was cultured for 72 h in various concentrations of elemental diet containing 3% thioglycollate, and the growth rate or activity of C. difficile was evaluated by Gram stain or by measuring optical density at 560 nm. Faecal samples from 10 healthy adults were cultured in elemental diet + 3% thioglycollate. RNA was extracted from faeces with glass powder, which can eliminate PCR inhibitors, and mRNA of C. difficile toxin B was measured by reverse transcription PCR. RESULTS: Maximum OD560 value during culture in thioglycollate-containing elemental diet was 2.4 times higher than that in thioglycollate alone (P = 0.0163). Viability of C. difficile was decreased in thioglycollate but not in thioglycollate-containing elemental diet. Toxin B mRNA was detected in five faecal samples (50%) before culture and in all samples after culture. CONCLUSIONS: Our results suggest that an elemental diet can modulate the growth of C. difficile in the gut flora.
Adult↗
Production of colony-stimulating factor in human dental pulp fibroblasts.
Class II major histocompatilibity complex (MHC)-expressing cells are usually distributed in dental pulp, and it was postulated that the colony-stimulating factor (CSF) derived from dental pulp fibroblasts contributes to the migration of class II MHC-expressing cells into pulp tissue. This study aimed to investigate the CSF production of human dental pulp fibroblasts. In pulp tissue sections, granulocyte (G)-CSF was detected from normal teeth, while G-CSF, macrophage (M)-CSF, and granulocyte-macrophage (GM)-CSF were detected from teeth with dentinal caries. In cultured dental pulp fibroblasts, G-CSF was detected by immunostaining, immunoprecipitation, and ELISA, and mRNAs of G-CSF, M-CSF, and GM-CSF were detected by RT-PCR. The dental pulp fibroblasts cultured with TNF-alpha were found to increase the G-CSF expression and to produce M-CSF and GM-CSF. These findings suggest that dental pulp fibroblasts usually produce G-CSF. In the presence of TNF-alpha, dental pulp fibroblast express M-CSF and GM-CSF.
Adolescent↗
Highly heterogeneous nature of delta-aminolevulinate dehydratase (ALAD) deficiencies in ALAD porphyria.
The properties of 9 delta-aminolevulinate dehydratase (ALAD) mutants from patients with ALAD porphyria (ADP) were examined by bacterial expression of their complementary DNAs and by enzymologic and immunologic assays. ALADs were expressed as glutathione-S-transferase (GST) fusion proteins in Escherichia coli and purified by glutathione-affinity column chromatography. The GST-ALAD fusion proteins were recognized by anti-ALAD antibodies and were enzymatically active as ALAD. The enzymatic activities of 3 ALAD mutants, K59N, A274T, and V153M, were 69.9%, 19.3%, and 41.0% of that of the wild-type ALAD, respectively, whereas 6 mutants, G133R, K59N/G133R, F12L, R240W, V275M, and delTC, showed little activity (< 8%). These variations generally reflect the phenotype of ALAD in vivo in patients with ADP and indicate that GST-ALAD fusion protein is indeed useful for predicting of the phenotype of ALAD mutants. The location of F12L mutation in the enzyme's molecular structure indicates that its disturbance of the quaternary contact of the ALAD dimer appears to have a significant influence on the enzymatic activity. Mouse monoclonal antibodies to human ALAD were developed that specifically recognized a carboxy terminal portion of ALAD, or other regions in the enzyme. This study represents the first complete analysis of 9 mutants of ALAD identified in ADP and indicates the highly heterogeneous nature of mutations in this disorder.
Adolescent↗
Loss of heterozygosity of the mannose 6-phosphate/insulin-like growth factor II receptor and p53 genes in human hepatocellular carcinoma.
Information about M6P/IGF2R and p53 genes in hepatocarcinogenesis is limited and controversial. We tested the loss of heterozygosity (LOH) of M6P/IGF2R and p53 genes in cirrhotic and neoplastic foci in surgically resected livers of 30 patients with hepatocellular carcinoma (HCC). The DNAs extracted from microdissected specimens were used for polymerase-chain-reaction (PCR)-based assay. LOH of the M6P/IGF2R gene in the primary HCCs was detected in 10 of 22 informative cases (45%). In five of these 10 cases (50%), LOH was detected in cirrhotic lesions adjacent to the HCCs. The allelic loss patterns of M6P/IGF2R in liver cirrhosis (LC) were identical to those in the corresponding HCC, suggesting that HCC could develop from one of the cells in which M6P/IGF2R had been lost. Furthermore, LOH of the p53 gene in HCC was detected in 10 (43%) of 23 informative cases, and p53 loss in cirrhotic foci adjacent to HCC was shown in one of the 10 cases (10%). The pattern of allelic loss of the p53 gene in the cirrhotic foci was identical with that in the corresponding tumor. The LOH of the M6P/IGF2R and p53 genes occurred independently in HCCs. LOH of the M6P/IGF2R locus was a relatively frequent and possibly early event in hepatocarcinogenesis, and LOH of the M6P/IGF2R gene and LOH of the p53 gene occurred independently.
Journal Article↗
Group C rotavirus NSP4 induces diarrhea in neonatal mice.
Nonstructural glycoprotein NSP4 of group A rotavirus induces diarrhea in neonatal mice by functioning as an enterotoxin. Previously, our laboratory reported that the structural features of group A and group C rotavirus NSP4 proteins are well conserved despite a lack of sequence homology between group A and group C rotavirus NSP4 proteins [Horie Y, et al., Arch Virol (1997) 142: 1865-1872]. To test whether group C rotavirus NSP4 has an enterotoxigenic activity, we expressed in Escherichia coli the carboxy two-thirds (corresponding to amino acid residues 55-150) of the NSP4 protein derived from group C rotavirus strain Ehime 9301. This truncated NSP4 protein was able to induce diarrhea in 5-day-old CD-1 mice when administered intraperitoneally. Thus, group C rotavirus NSP4 acts as an enterotoxin like group A rotavirus NSP4.
Animal Population Groups↗
Liver dysfunction elicited by gut ischemia-reperfusion.
Gut ischemia and reperfusion (I/R) has been implicated as a prime mechanism in the pathogenesis of multiple organ failure and in initiating remote organ failure. Although it has long been known that gut I/R elicits liver dysfunction, only recently has the kinetics of leukocyte accumulation in the hepatic microcirculation and mechanisms of the liver injury after gut I/R been investigated. These studies reveal that the magnitude of gut I/R-induced liver injury depends on the duration of ischemic period and animal species. Gut I/R-induced accumulation of leukocytes, both neutrophils and lymphocytes, in the liver results in an oxidative stress in proximity to non-perfused sinusoid that contributes to subsequent hepatocellular injury. The gut I/R-induced leukosequestration in the liver is mediated by adhesion molecules that are induced by different cytokines, endotoxin, and oxidants. Kupffer cells also play an important role in the gut I/R-induced leukosequestration and liver injury. Nitric oxide and anti-oxidants such as superoxide dismutase protect the liver against the deleterious effects of gut I/R. Furthermore, agents such as ethanol can alter the hepatic responses to gut I/R. The results of these studies provide novel information and potential therapeutic strategies for reducing the liver dysfunction and multiple organ failure induced by gut I/R.
Journal Article↗
Role of endothelin in endotoxin-induced hepatic microvascular dysfunction in rats fed chronically with ethanol.
BACKGROUND: We examined the role of endothelin in endotoxin-induced hepatic microcirculatory disturbance in pair-fed rats given a liquid diet containing ethanol or isocaloric control. METHODS AND RESULTS: One lobe of the liver was observed with the use of an intravital microscope. Erythrocytes (RBCs) labeled with fluorescein isothiocyanate (FITC) were injected, and the flow velocity of the FITC-RBCs in the sinusoids was measured with an off-line velocimeter. The flow velocity decreased 30 min after 1 mg/kg of lipopolysaccharide (LPS) was administered to the controls, and portal pressure (PP) was increased at 60 min. In ethanol-fed rats, however, both the flow velocity and PP increased in the early phase (at 10 min), and in the late phase, flow velocity decreased and PP increased more than in the controls. The LPS-induced decrease in flow velocity was blunted, when BQ-123, an antagonist of endothelin receptor subtype A, was infused into ethanol-fed rats, and BQ-123 also attenuated the change in PP. The plasma endothelin levels in both systemic and portal blood of the ethanol-fed rats were higher than in the controls. CONCLUSIONS: These results suggest that endothelin plays a role in the LPS-induced hepatic microcirculatory disturbance, especially in alcohol-fed animals.
Alanine Transaminase↗
A Japanese herbal medicine, Sho-saiko-to, prevents gut ischemia/reperfusion-induced hepatic microvascular dysfunction in rats.
BACKGROUND AND AIM: We have reported that gut ischemia/reperfusion (I/R) causes hepatic microvascular dysfunction. Nitric oxide (NO) has been found to be a modulator of the adhesive interactions between leukocytes, platelets, and endothelial cells. Sho-saiko-to (TJ-9), a Japanese herbal medicine, is reported to have protective effects against liver injury and to regulate NO production. The objective of this study was to determine whether TJ-9 affects hepatic microvascular dysfunction elicited by gut I/R, and to investigate the role of NO. METHODS: Male Wistar rats were exposed to 30 min of gut ischemia followed by 60 min of reperfusion. Intravital microscopy was used to monitor leukocyte recruitment and the number of non-perfused sinusoids (NPS). Plasma tumor necrosis factor (TNF)-alpha and alanine aminotransferase (ALT) activities were measured. In another set of experiments, TJ-9 (1 g/kg per day intragastrically) was administered to rats for 7 days. In some experiments, dexamethasone (ST) (2 mg/kg per day intravenously) was administered. RESULTS: In control rats, gut I/R elicited increases in the number of stationary leukocytes, NPS, and plasma TNF-alpha and ALT activities, and these changes were mitigated by the pretreatment with TJ-9. Pretreatment with an NO synthase inhibitor diminished the protective effects of TJ-9 on the increase in leukostasis in the pericentral region, NPS, and plasma TNF-alpha levels, but not its effect on the increase in leukostasis in the midzonal region, total number of stationary leukocytes, or plasma ALT activities. Pretreatment with TJ-9 increased plasma nitrite/nitrate levels. The responses caused by gut I/R were attenuated by the pretreatment with ST. Pretreatment with an NO synthase inhibitor did not affect the effect of ST. CONCLUSIONS: These results suggest that TJ-9 attenuates the gut I/R-induced hepatic microvascular dysfunction and inflammatory responses such as TNF-alpha production in the early phase via enhancement of NO production, and sequential hepatocellular damage via its anti-inflammatory effect like corticosteroid effect.
Animals↗
Left ventricular epicardial outflow tract tachycardia: a new distinct subgroup of outflow tract tachycardia.
The present study investigated the incidence and ECG characteristics of ventricular tachycardias (VTs) originating from the left ventricular (LV) epicardium. Thirty-one consecutive patients with VT or premature ventricular contraction originating from the outflow tract (OT-VT) underwent catheter ablation. Twenty-one OT-VTs were ablated from the endocardium in the right ventricular (RV) OT and 3 were ablated from the endocardium in the LVOT. In the remaining 7 patients, 4 (13%) OT-VTs were LV epicardial in origin, and 1 of these was ablated from the left sinus of Valsalva. The ECG characteristics of OT-VT of epicardial origin included prominent tall R-waves in the inferior leads, an R-wave in V1 and an S-wave in V2, precordial R-wave transition in V2-4, a deep QS-wave in aVL, and no S-wave in V6. In addition, there was an atypical left bundle branch block morphology with an inferior axis. These findings were observed during pacing from several sites in the LV epicardium. Furthermore, pacing from the left sinus of Valsalva caused a relatively tall R in V1, deep S-wave in V2 and a tall R-wave with a shallow S-wave in V3, as well as tall R-waves in the inferior leads, which represented intermediate characteristics between RV endocardial OT-VT and LV endocardial OT-VT. In conclusion, OT-VT originating from the LV epicardium is not uncommon and has characteristic ECG findings. Some of them can be ablated from the left sinus of Valsalva.
Adult↗
Atrial blood cyst in an adult with regurgitation of mitral and tricuspid valves.
Blood cysts of the heart are extremely rare in adults and usually involve valves or the left ventricle. Although two cases of blood cysts in the right atrium in adults have been reported, a cyst combined with a disorder of the valves has never been reported. We report a 52-year-old woman with a blood cyst that generated from the right atrial septum. Furthermore, the patient had regurgitation of both the mitral and tricuspid valves and then underwent surgical excision of the blood cyst, mitral valve plasty and tricuspid valve annuloplasty. We believe that it is possible to diagnose blood cysts with echocardiography, CT and magnetic resonance imaging. Echocardiography showed the cyst as a circle without a complete inner free-echo. CT and magnetic resonance imaging showed a mass with a non-enhanced inner structure. Furthermore, the latter showed a cyst that was enhanced by T1- but not T2-weighted images, indicating that the content of the cyst was a persistent substance such as blood. Concerning the generation of blood cysts, we hypothesize that heteroplastic growth arising from primitive pericardial mesothelium causes disorders of valves and blood cysts.
Blood↗
[Effect of alcohol on organ microcirculation: its relation to hepatic, pancreatic and gastrointestinal diseases due to alcohol].
Although alcohol is well recognized as a systemic toxin, the enteric manifestations of alcohol abuse have only recently begun to be elucidated at the cellular and microvascular levels. Since the microvascular mechanism of the toxicity of alcohol has progressively been revealed, clinical applications of this research field should increase the availability of therapeutic options for alcohol-induced injuries of liver, pancreas and gastrointestinal (GI) tract. A high concentration of ethanol reduces GI and pancreas blood flow. Ethanol-induced GI hemorrhage, GI ulcer, and pancreatitis are initiated by the microcirculatory disturbance of GI mucosa and pancreas. Ethanol administration induces an increase in vasoactive agents such as endothelin and nitric oxide and oxidative stress. They appear to be involved in ethanol-induced GI and pancreatic injury. Regarding the effects of ethanol on the liver, small amount of ethanol increases hepatic blood flow, and prevents gut ischemia/reperfusion (I/R)-induced hepatic microvascular dysfunction and subsequent liver injury. While large amount of ethanol itself causes hepatic microvascular dysfunction, and aggravates the gut I/R-induced hepatic microvascular dysfunction and subsequent liver injury. Vasoactive agents and oxidative stress also appear to be involved in the liver injury. In endotoxemic animals, even small amount of ethanol causes hepatic microvascular dysfunction. Chronic ethanol consumption aggravates endotoxin-induced hepatic microvascular dysfunction. Chronic ethanol consumption aggravates gut I/R-induced leukostasis in the liver and hepatocellular injury associated with an enhanced expression of adhesion molecules, while it prevents the gut I/R-induced sinusoidal perfusion injury. Thus, effects of chronic ethanol consumption on the I/R injury are still controversial.
Animals↗
Molecular analysis of delta-aminolevulinate dehydratase deficiency in a patient with an unusual late-onset porphyria.
Cloning, expression, and genotype studies of the defective gene for delta-aminolevulinate dehydratase (ALAD) in a patient with an unusual late onset of ALAD deficiency porphyria (ADP) were carried out. This patient was unique in that he developed the inherited disease, together with polycythemia, at the age of 63. ALAD activity in erythrocytes of the patient was less than 1% of the normal control level. ALAD complementary DNA (cDNA) isolated from the patient's Epstein-Barr virus (EBV)-transformed lymphoblastoid cells had 2 base transitions in the same allele, G(177) to C and G(397) to A, resulting in amino acid substitutions K59N and G133R, respectively. It has been verified that the patient had no other ALAD mutations in this and in the other allele. By restriction fragment length polymorphism (RFLP) analysis, all family members of the proband who had one-half ALAD activity compared with the ALAD activity of the healthy control were shown to have the same set of base transitions. Expression of ALAD cDNA in CHO cells revealed that K59N cDNA produced a protein with normal ALAD activity, while G133R and K59N/G133R cDNA produced proteins with 8% and 16% ALAD activity, respectively, compared with that expressed by the wild type cDNA. These findings indicate that while the proband was heterozygous for ALAD deficiency, the G(397) to A transition resulting in the G133R substitution is responsible for ADP, and the clinical porphyria developed presumably due to an expansion of the polycythemic clone in erythrocytes that carried the mutant alad allele.
Age of Onset↗
Colorectal carcinomas in mice lacking the catalytic subunit of PI(3)Kgamma.
Phosphoinositide-3-OH kinases (PI(3)Ks) constitute a family of evolutionarily conserved lipid kinases that regulate a vast array of fundamental cellular responses, including proliferation, transformation, differentiation and protection from apoptosis. PI(3)K-mediated activation of the cell survival kinase PKB/Akt, and negative regulation of PI(3)K signalling by the tumour suppressor PTEN (refs 3, 4) are key regulatory events in tumorigenesis. Thus, a model has arisen that PI(3)Ks promote development of cancers. Here we report that genetic inactivation of the p110gamma catalytic subunit of PI(3)Kgamma (ref. 8) leads to development of invasive colorectal adenocarcinomas in mice. In humans, p110gamma protein expression is lost in primary colorectal adenocarcinomas from patients and in colon cancer cell lines. Overexpression of wild-type or kinase-dead p110gamma in human colon cancer cells with mutations of the tumour suppressors APC and p53, or the oncogenes beta-catenin and Ki-ras, suppressed tumorigenesis. Thus, loss of p110gamma in mice leads to spontaneous, malignant epithelial tumours in the colorectum and p110gamma can block the growth of human colon cancer cells.
Adenocarcinoma↗
Sorbitol as an arrester of embryonic development in diapausing eggs of the silkworm, Bombyx mori.
Recently, it was confirmed that embryos derived from diapausing eggs of the silkworm, Bombyx mori, begin their development and reach larval maturity on mulberry leaves, when the naked eggs are cultured in vitro. In this study, we found that the method of embryo culture is useful for determining the physiological regulation of diapause. We show that the development of embryos derived from diapausing eggs was strongly inhibited by the addition of either sorbitol or trehalose to the culture medium. Furthermore, this inhibitory effect disappeared when the embryos were cultured in a control medium which did not contain either sorbitol or trehalose, indicating that the inhibitory reactions caused by both substances are reversible. The minimal effective dose of either sorbitol or trehalose was approximately 0.2 M, a value similar to the in vivo concentration of sorbitol in diapausing eggs (0.2 M). Glycerol, mannitol or glucose were moderately effective for inhibition. Sorbitol present in diapausing silkworm eggs does not appear to serve as an antifreeze, but as an strong arresting factor of embryonic development. Furthermore, these results show that a decrease in sorbitol releases the embryos from diapause at the termination of diapause.
Journal Article↗
Predictive factors for intrahepatic recurrence after percutaneous ethanol injection therapy for small hepatocellular carcinoma.
BACKGROUND: Percutaneous ethanol injection therapy has been used widely for small hepatocellular carcinoma. This study was undertaken to determine factors predictive of local recurrence or new nodular recurrence in patients with small hepatocellular carcinoma treated with percutaneous ethanol injection. METHODS: The authors studied 73 nodules treated with percutaneous ethanol injection in 49 patients with small hepatocellular carcinoma. The usefulness of predictive factors for recurrence was assessed with the Kaplan-Meier method. The clinicopathologic variables examined included age, gender, Child-Pugh classification, number of tumors (single vs. multiple), tumor size, degree of tumor differentiation, ultrasonographic findings such as peripheral hypoechoic band (so-called 'halo'), intratumoral echo pattern, tumor staining on enhanced computed tomography, combination therapy with transcatheter arterial embolization, and serum alpha-fetoprotein level. RESULTS: The local recurrence rates were 19%, 27%, 33%, 33%, and 33%, respectively, and the new nodular recurrence rates were 19%, 51%, 74%, 83%, and 83%, respectively, at 1, 2, 3, 4, and 5 years after percutaneous ethanol injection therapy. The frequency of local recurrence was associated with the histologic differentiation of more than moderately differentiated (P < 0.001), presence of a sonographic halo (P < 0. 005), an intratumoral heterogeneous echo pattern (P < 0.001), and positive tumor staining on enhanced computed tomography (P < 0.01). Multivariate analysis showed that the presence of a halo and an intratumoral heterogeneous echo pattern were the most important variables for predicting local recurrence. The frequency of new nodular recurrences was related to the presence of multiple tumors (P < 0.01) and a high serum alpha-fetoprotein level (P < 0.001). Multivariate analysis showed that a high serum alpha-fetoprotein level was a reliable predictor of new nodular recurrence. CONCLUSIONS: This study showed that the presence of a halo and an intratumoral echo pattern on ultrasonography were useful predictors for local recurrence after percutaneous ethanol injection therapy for small hepatocellular carcinoma, and that a high serum alpha-fetoprotein level was associated with a higher frequency of new nodular recurrences.
Adult↗