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Biomedical subjects

T Ueno

Publications and source records attributed to T Ueno.

At least 127 records · Page 7Linked to original sources
PubMed2000

Ursodeoxycholic acid reduces expression of heat shock proteins in primary biliary cirrhosis.

BACKGROUND: To identify injured cells in the liver of patients with primary biliary cirrhosis (PBC) and to determine the effects of ursodeoxycholic acid (UDCA) on these cells, we examined the cellular expression of heat shock proteins (HSPs) in PBC both before and after treatment with UDCA. METHODS: Expression of HSP70 and ubiquitin in PBC livers (n=34) was evaluated immunohistochemically as well as by immunoblot analysis, and compared with chronic viral hepatitis type C (n= 9), primary sclerosing cholangitis (n=8), and controls (n=7). RESULTS: Immunoblot analysis demonstrated a marked expression of HSP70 and ubiquitin in PBC. Immunohistochemical staining for both HSP70 and ubiquitin was observed to be strong in biliary epithelial cells (BECs) and moderate in both hepatocytes and arteries in PBC. Cellular labelling rates for HSP70 and ubiquitin of bile ducts in PBC were significantly higher (p<0.01) than those in chronic viral hepatitis type C, primary sclerosing cholangitis, or controls. The labelling rates for HSP70 and ubiquitin in bile ducts and in hepatocytes were significantly decreased (p<0.01) after treatment with UDCA in PBC. CONCLUSIONS: The present data suggest that BECs and hepatocytes significantly express HSPs even in the early stages of PBC, and that UDCA treatment significantly improves their condition. The immunohistochemical evaluation of HSPs is a valid and sensitive means to identify injured cells in PBC.

Adult↗
PubMed2000

Detection of hepatitis C virus RNA in oral lichen planus and oral cancer tissues.

Hepatitis C virus (HCV) infection not only causes chronic liver diseases but shows extrahepatic manifestations as oral lichen planus (OLP) and oral cancer. To elucidate the direct relationships among these diseases and HCV infection, we investigated the detection of positive- and negative-strand HCV-RNA from serum, OLP (n=19), and oral cancer (n=17) tissues. We used a sensitive reverse transcription to polymerase chain reaction (RT-PCR) method, and analyzed sequences from the HCV El/E2 region of the genome from serum and tissue. Positive and negative HCV-RNA strands were observed in 13 (92.9%) and 3 (21.4%) OLP tissues, respectively. In oral cancer tissues, positive HCV-RNA strands were detected in all tissues from anti-HCV positive patients. Negative HCV-RNA strands were observed in 5 of 7 (71.4%) patient's tissues. Furthermore, it was confirmed that the sequence from one of each OLP and oral cancer patient differed between serum and tissue HCV-RNA. These results may indicate that HCV persists and replicates in these lesions, suggesting a pathological role for HCV, although the mechanisms are unclear.

Adult↗
PubMed2000

Influence of protrusive tooth contact on tapping point distribution.

This study investigated the influence of protrusive tooth contacts (tooth contacts during mandibular protrusion) on the tapping point distribution. Nine healthy subjects volunteered for this study and the protrusive tooth contact pattern, as well as the retrusive tooth contact pattern, was altered on four maxillary occlusal splints. The first splint was adjusted to make the sagittal incisal path of protrusion and retrusion equivalent to that of the natural dentition. The second and third splints had partial and complete elimination of the protrusive tooth contact, respectively. The fourth splint had complete elimination of both protrusive and retrusive tooth contacts. The subjects were asked to use each splint continuously for 1 week. The tapping point distribution was measured on the 7th day after insertion of each splint. The four experimental occlusal conditions were found to have a significant effect on the tapping point distribution. The complete elimination of the protrusive tooth contact caused an anterior tapping point location and an increase in the tapping point area. The former tendency was found to be independent of the presence of the retrusive tooth contact. In conclusion, it was suggested that the protrusive tooth contact plays a significant role in maintaining the consistency and stability of the tapping point.

Adult↗
PubMed2000

Cholestasis with altered structure and function of hepatocyte tight junction and decreased expression of canalicular multispecific organic anion transporter in a rat model of colitis.

Cholestasis is frequently associated with inflammatory bowel disease. Because some cholestasis is resulted from altered hepatocyte tight junctions (TJs) or the canalicular multispecific organic anion transporter, we have investigated the following topics in a rat model of inflammatory bowel disease: (1) alterations in hepatocyte TJs and in the canalicular multispecific organic anion transporter, (2) etiologic factors for cholestasis, and (3) effects of antibiotics on cholestasis. Rats with trinitrobenzene sulfonic acid-induced colitis were studied 24 hours after treatment. Hepatocyte TJs and the canalicular multispecific organic anion transporter were evaluated by immunostaining for TJ-associated proteins, 7H6 and ZO-1, and multidrug resistance protein 2 (mrp2). To investigate etiologic factors causing cholestasis, portal endotoxin and proinflammatory cytokines were examined. The effects of polymyxin B, penicillin G, or metronidazole on immunostaining for 7H6, ZO-1, mrp2, and cholestasis were investigated. (1) Immunostaining for 7H6 and ZO-1 colocalized outlining the bile canaliculi and immunostaining for mrp2 localized on the canalicular membrane in controls. Treatment with trinitrobenzene sulfonic acid induced significant cholestasis and caused translocation of immunostaining for 7H6, but not that for ZO-1, to the cytoplasm and diminished immunostaining for mrp2 on the canaliculus membrane. (2) The levels of portal endotoxin, but not proinflammatory cytokines, was increased. (3) Polymyxin B, but not the other antibiotics, prevented alterations in immunostaining for both 7H6 and mrp2, and cholestasis. We described that both hepatocyte TJs and the canalicular multispecific organic anion transporter were altered and that gut-derived endotoxin levels in the portal blood were increased in this rat colitis model.

Animals↗
PubMed2000

Inhibition of transforming growth factor beta prevents progression of liver fibrosis and enhances hepatocyte regeneration in dimethylnitrosamine-treated rats.

We investigated whether anti-transforming growth factor beta (TGF-beta) molecular intervention can halt the progression of liver fibrosis in rats. To block TGF-beta action in a specific manner, we prepared an adenovirus expressing a truncated type II TGF-beta receptor (AdTbeta-TR), which specifically inhibits TGF-beta signaling as a dominant-negative receptor. We also used an adenovirus expressing bacterial beta-galactosidase (AdLacZ) as a control adenovirus. Rats were treated with dimethylnitrosamine (DMN) for 3 weeks; then, AdTbeta-TR, AdLacZ, or saline was intravenously applied once, followed by an additional 3-week DMN treatment. The ratio between the truncated receptor and the wild-type receptor at the mRNA level was 15 at 1 week and 10 at 3 weeks after gene transfer. Immunohistostaining analysis showed that the truncated receptor was expressed mainly in septal cells including hepatic stellate cells. Liver fibrosis, as assessed by histology, hydroxyproline content, and the serum level of hyaluronic acid, progressed during the additional 3-week DMN treatment. However, in rats infected with AdTbeta-TR, the fibrosis remained at the level seen in rats given DMN for only 3 weeks. All AdTbeta-TR-treated rats remained alive, whereas DMN-treated rats infused with either AdLacZ or saline died of liver dysfunction. In the livers of AdTbeta-TR-treated rats, electron microscopy showed: 1) less accumulation of extracellular matrix proteins in the Disse's spaces; 2) regenerated hepatocytes; and 3) fat droplet-rich "quiescent" hepatic stellate cells. Our results demonstrate that TGF-beta plays a critical role in the progression of liver fibrosis, and suggest that anti-TGF-beta intervention should be therapeutic in already-established fibrotic livers, not only by suppressing fibrosis, but by facilitating hepatocyte regeneration.

Animals↗
PubMed2000

Tissue factor expression in breast cancer tissues: its correlation with prognosis and plasma concentration.

Tissue factor (TF), an initiator of the extrinsic coagulation cascade, is expressed in a wide range of cancer cells and plays important roles in cancer progression and metastasis. Recently, the intracellular function of TF has been revealed to be involved in cancer invasion, independent of the blood coagulation pathway. To evaluate the clinical significance of TF expression, we performed an enzyme-linked immunosorbent assay (ELISA) in the plasma of 67 breast cancer patients and immunohistochemistry in 213 breast cancer tissues. In the ELISA study, we showed an up-regulation of plasma TF concentration in breast cancer patients compared with normal controls. Immunohistochemistry demonstrated that TF was expressed in tumour cells and stromal cells and tumour TF expression closely correlated with stromal TF expression (P = 0.0005). The concentration of plasma TF was associated with tissue TF expression in both tumour and stroma. The multivariate analysis demonstrated that tumour TF expression was an independent prognostic indicator for overall survival (P = 0.0452). Our data show that plasma TF concentration reflects tissue TF expression and tumour TF expression can provide some predictive value for prognosis and distant metastasis, which indicates the importance of TF function in tumour progression.

Adult↗
PubMed2000

Detection of human alpha-defensin-1, an antimicrobial peptide, in the fluid of jaw cysts.

OBJECTIVE: The purpose of this study was to isolate and to identify an antimicrobial peptide, human alpha-defensin-1 (HNP-1) in jaw cyst fluid. STUDY DESIGN: We collected jaw cyst fluid from 22 patients with various jaw cysts and analyzed the peptide components of them by reversed-phase high-performance liquid chromatography (HPLC). HNP-1 in the jaw cyst fluid was identified by the amino acid sequence and the molecular weight. The concentration of HNP-1 in the fluid of various jaw cysts was quantified by HPLC. RESULTS: HNP-1 in the jaw cyst fluid was isolated, purified, and identified. The concentrations of HNP-1 in the jaw cyst fluid ranged from 27.0 to 3725.4 microg/mL. CONCLUSION: HNP-1 was detected in the fluid of various types of jaw cysts.

Adolescent↗
PubMed2000

Neuropsychological EEG activation in patients with epilepsy.

To examine the effects of higher mental activity on the EEG, 480 Japanese patients with different types of epilepsy were subjected to potentially provocative cognitive tasking, termed 'neuropsychological EEG activation' (NPA), during standard EEG recordings. NPA tasks consisted of reading, speaking, writing, written arithmetic calculation, mental arithmetic calculation and spatial construction. The NPA tasks provoked epileptic discharges in 38 patients (7.9%) and were accompanied by myoclonic seizures in 15 patients, absence seizures in eight and simple partial seizures in one. Among the cognitive tasks, mental activities mainly associated with use of the hands, i.e. writing (68.4%), written calculation (55. 3%) and spatial conction (63.2%), provoked the most discharges, followed by mental calculation (7.9%) and reading (5.3%). Detailed examination of the precipitating events revealed action-programming type activities to be the most crucial in 32 out of the 38 patients (84.2%), followed by thinking type activities in four patients (10. 5%). Regarding the classification of epilepsies proposed by the International League Against Epilepsy, seizure-precipitating mental activities in our series were almost exclusively (in 36 out of the 38 patients) related to idiopathic generalized epilepsies (IGEs) including juvenile myoclonic epilepsy, juvenile absence epilepsy, grand mal epilepsy on awakening and childhood absence epilepsy, and were rarely (in only two out of the 38 patients) related to temporal lobe epilepsy. In our IGE patients, the provocative effects of NPA were related to myoclonic seizures rather than absence or generalized tonic-clonic seizures. These results suggest that NPA is a useful tool for examining the relationship between cognitive function and epileptic seizures, and that the IGE patients with myoclonic seizures are vulnerable to higher mental activities requiring action-programming or thinking.

Adolescent↗
PubMed2000

Genetic regulation of anti-erythrocyte autoantibodies and splenomegaly in autoimmune hemolytic anemia-prone new zealand black mice.

New Zealand Black (NZB) mice spontaneously produce anti-erythrocyte autoantibodies (AEA) in association with splenomegaly, thus serving as a model for autoimmune hemolytic anemia. Although these autoimmune traits are inherited as a dominant fashion, expression in F(1) hybrids of NZB and most non-New Zealand strains is suppressed due to the contribution of wild-type modifying genes present in the latter strains. Using chromosomal microsatellite markers in the (C57BL/6 x NZB)F(1) x NZB backcross progeny, we mapped C57BL/6 modifying loci for AEA production and splenomegaly. Generation of AEA was found to be down-regulated by a combined effect of two major independently segregating dominant alleles-one linked to D7MIT30 on chromosome 7 and the other linked to D10MIT42 on chromosome 10. Splenomegaly was modified mainly by a single C57BL/6 allele linked to D4MIT58 on chromosome 4. Thus, the autoimmune hemolytic anemia in the NZB strain is under multigenic control and a combined action of not only susceptibility but also modifying alleles with suppressive activities affects the outcome of disease features in the progeny. There are potentially important candidate genes which may be linked to the regulation of AEA and splenomegaly.

Anemia, Hemolytic, Autoimmune↗
PubMed2000

Isolation and characterization of monoclonal antibodies that inhibit hepatitis C virus NS3 protease.

A series of mouse monoclonal antibodies (MAbs) to the nonstructural protein 3 (NS3) of hepatitis C virus was prepared. One of these MAbs, designated 8D4, was found to inhibit NS3 protease activity. This inhibition was competitive with respect to the substrate peptide (K(i) = 39 nM) but was significantly decreased by the addition of the NS4A peptide, a coactivator of the NS3 protease. 8D4 also showed marked inhibition of the NS3-dependent cis processing of the NS3/4A polyprotein but had virtually no effect on the succeeding NS3/4A-dependent trans processing of the NS5A/5B polyprotein in vitro. Epitope mapping of 8D4 with a random peptide library revealed a consensus sequence, DxDLV, that matched residues 79 to 83 (DQDLV) of NS3, a region containing the catalytic residue Asp-81. Furthermore, synthetic peptides including this sequence were shown to block the ability of 8D4 to bind to NS3, indicating that 8D4 interacts with the catalytic region of NS3. The data showing decreased inhibition potency of 8D4 against the NS3/4A complex suggest that 8D4 recognizes the conformational state of the protease active site caused by the association of NS4A with the protease.

Amino Acid Sequence↗
PubMed2000

Increased migration in late G(1) phase in cultured smooth muscle cells.

Migration and proliferation of smooth muscle cells (SMC) contribute to neointimal formation after arterial injury. However, the relation between migration and proliferation in these cells is obscure. To discriminate between migration and proliferation, we employed a migration assay of SMC at different phases of the cell cycle. Serum-deprived SMC were synchronized in different phases of the cell cycle by addition of serum for various periods of time. Migration induced by platelet-derived growth factor B-chain homodimer was maximal in SMC that were predominantly in the late G(1) (G(1b)) phase. In addition, in nonsynchronized SMC, 65-75% of SMC that had migrated were in the G(1b) phase. Phosphorylated myosin light chain was enriched around the cell periphery in SMC in the G(1b) phase compared with SMC in the other cell cycle phases. Interestingly, the Triton X-100-insoluble fraction of myosin was remarkably decreased in G(1b)-enriched SMC. These findings suggest that migratory activity of SMC may be coupled with the G(1b) phase. The phosphorylation and retention of myosin might explain some of the properties responsible for increased migration.

Actins↗
PubMed2000

Suppressive effect of topically applied CX-659S, a novel diaminouracil derivative, on the contact hypersensitivity reaction in various animal models.

BACKGROUND: The T-cell-mediated contact hypersensitivity reaction (CHR) is thought to be involved in the pathogenesis of clinical cutaneous disorders including atopic dermatitis. A novel diaminouracil derivative, CX-659S, has been reported to have an inhibitory activity against picryl chloride (PC)-induced CHR when administered either orally or percutaneously. The inhibitory effect of topical CX-659S was assessed in three CHR models in the present study. In addition, to elucidate the mechanism of action of this compound, we examined the effect of CX-659S on the expression of messenger RNAs for proinflammatory cytokines after elicitation in PC models. METHODS: For the in vivo evaluation of the efficacy of CX-659S, we used PC- or oxazolone-induced CHR in mice and 2,4-dinitrochlorobenzene (DNCB)-induced CHR in guinea pigs. CX-659S was topically applied immediately after the hapten challenge in each model. To assess the effect on gene expression of cytokines, we used the reverse transcriptase-polymerase chain reaction (RT-PCR), a semiquantitative technique with specific primers. RESULTS: Topical CX-659S dose-dependently inhibited ear swelling at 24 h after the challenge in the two mouse models. This inhibitory effect was histologically confirmed in the PC model. Topically applied CX-659S also inhibited erythema and edema formation 24 h after challenge in the guinea pig model. CX-659S inhibited the expression of mRNA for proinflammatory cytokines IL-1 beta and TNF-alpha in vivo. CONCLUSIONS: Topically applied CX-659S showed significant inhibitory activities against CHR models both in mice and in guinea pigs. Inhibition profiles of CX-659S toward mRNA expression for proinflammatory cytokines corroborated these findings. CX-659S thus could be a useful therapeutic agent for allergic cutaneous disorders such as allergic contact dermatitis and atopic dermatitis.

Administration, Topical↗
PubMed2000

Structure-activity relationship of orally potent tripeptide-based HIV protease inhibitors containing hydroxymethylcarbonyl isostere.

We designed and synthesized a new class of peptidomimetic human immunodeficiency virus protease inhibitors containing a unique unnatural amino acid, allophenylnorstatine [Apns; (2S,3S)-3-amino-2-hydroxy-4-phenylbutyric acid], with a hydroxymethylcarbonyl isostere as the active moiety. From a structure-activity relationship study of HIV-1 protease inhibition, enzyme selectivity for other aspartyl proteases, the antiviral activity and pharmacokinetics in rats, 24c (KNI-227) and 24d (KNI-272, our first clinical candidate) were found to be selective and orally potent HIV protease inhibitors. Moreover, an improvement of the pharmacokinetic features of KNI-272 provided two long-lasting and highly bioavailable compounds (24g: JE-2178, 24h: JE-2179).

Animals↗
PubMed2000

Abnormal myocardial blood flow distribution in patients with angina pectoris and normal coronary arteriograms.

To evaluate coronary microvascular function and its relation to the genesis of chest pain and ST-segment depression during exercise in patients with syndrome X, pacing-induced changes in transmural myocardial blood flow distribution were quantitatively assessed by 2-dimensional myocardial contrast echocardiography. Of 25 patients with a history of chest pain and normal coronary arteries with the negative ergonovine test, 11 had exercise-induced chest pain and ST-segment depression (syndrome X), and 14 did not (controls). Myocardial blood flow distribution before and after pacing stress was assessed by measuring the ratio of the endocardial to epicardial gray level (ie, endo/epi gray level ratio) in the territory of the left anterior descending coronary artery. Pacing-induced chest pain and ST-segment depression were observed in syndrome X, but not in controls. The endo/epi gray level ratio in syndrome X significantly decreased after pacing (from 0.98+/-0.10 to 0.76+/-0.17, p<0.01), but not in controls (from 0.97+/-0.08 to 0.99+/-0.08, NS). Abnormal myocardial blood flow distribution may play an important role in exercise-induced chest pain and ST-segment depression in these patients.

Adult↗
PubMed2000

The physiological activity and in vivo distribution of dinitrosyl dithiolato iron complex.

Nitric oxide (NO) is recognized as an endogenous mediator of vascular tone, a neurotransmitter and an immune effector molecule. Furthermore, it has been implicated in the development of various diseases. Because NO is extremely labile in the biological milieu, its activities can be effected not only by NO itself but also by relatively stable physiologic NO carriers or NO donors. Dinitrosyl iron complexes have been recognized as endogenous NO carrier molecules as well as S-nitrosothiols. The complex has been found in cells and the tissues of mammals and bacteria via its readily detectable, characteristic electron paramagnetic resonance (EPR) signals. Endogenously produced dinitrosyl iron complex with thiolate ligands (DNIC) has a critical biological potential; and it can function as a physiologic regulatory factor in a biological system, especially the immune and cardiovascular systems. We have been studying the in vivo behavior and distribution of DNIC to elucidate its physiological roles and pharmacokinetics. In this article, an attempt is made to provide an overview of the history, physiology and in vivo behavior of DNIC.

Animals↗
PubMed2000

Binding affinity of the methyl ester of AK-toxin I to membrane fractions from Japanese pear leaves.

The binding site of AK-toxin, a host-specific toxin against Japanese pear, was searched for in the membrane fractions of the pear leaves, using 3H-labeled AK-toxin I methyl ester. Binding activity, which was displaceable by the unlabeled ligand, was observed for microsomal fraction from a toxin-susceptible cultivar, Nijisseiki. However, the binding was also observed for those from toxin-resistant cultivars, Kosui and Hosui. Detection of the specific binding failed for the plasma membrane fraction which was prepared from microsomal fraction of the toxin-susceptible cultivar by aqueous two-phase separation, and the hitherto presumed model of the AK-toxin receptor in the plasma membrane could not be verified.

Binding, Competitive↗
PubMed2000

Absolute structure of N-p-coumaroyloctopamine in elicitor-treated potato tuber tissue.

Treatment of potato tuber tissue with beta-1,3-oligoglucosaccharide causes an accumulation of N-p-coumaroyloctopamine (1). In order to determine the absolute structure of 1 in potato, optically active 1 was synthesized from (R)-octopamine which had been obtained from the racemic mixture by the fractional crystallization. By comparing the chromatographic behavior of synthetic and naturally-occurring samples with a chiral HPLC analysis, the absolute configuration of 1 in potato was determined to be S. This indicates that the absolute configuration of the octopamine moiety of 1 is opposite to that of octopamine formed in animal tissues.

Coumaric Acids↗