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Biomedical subjects

T Ueno

Publications and source records attributed to T Ueno.

At least 181 records · Page 10Linked to original sources
PubMed1999

Increased expression of membrane type 1 matrix metalloproteinase and matrix metalloproteinase-2 with tumor dedifferentiation in hepatocellular carcinomas.

Destruction of the extracellular matrices is required for tumor invasion and metastasis. Matrix metalloproteinase-2 degrades type IV collagen and laminin, major components of the basement membrane. Membrane type 1 matrix metalloproteinase activates the latent form of matrix metalloproteinase-2. We studied changes in membrane type 1 matrix metalloproteinase and matrix metalloproteinase-2 expression in relation to the tumor differentiation of hepatocellular carcinomas. Activity of matrix metalloproteinase-2 was also evaluated in hepatocellular carcinomas and noncancerous tissues. Overall, 37 hepatocellular carcinomas were studied. Expression of membrane type 1 matrix metalloproteinase and matrix metalloproteinase-2 was determined by either immunohistochemistry (n=37) or in situ hybridization (n=6). Changes in membrane type 1 matrix metalloproteinase and matrix metalloproteinase-2 expression were evaluated in relation to tumor differentiation. Gelatinolytic activities were analyzed by gelatin zymography (n=4). Membrane type 1 matrix metalloproteinase and matrix metalloproteinase-2 were detected in hepatoma cells and stromal cells. In addition, these matrix metalloproteinases were detected in the same hepatoma cells. Increased expression of membrane type 1 matrix metalloproteinase and matrix metalloproteinase-2 was associated with tumor dedifferentiation. The active form of matrix metalloproteinase-2 was more strongly expressed by hepatocellular carcinomas than by noncancerous tissues. These findings indicate that increased expression of membrane type 1 matrix metalloproteinase and matrix metalloproteinase-2 was associated with tumor dedifferentiation, suggesting that these matrix metalloproteinases are intimately involved in the invasion of hepatocellular carcinomas.

Adult↗
PubMed1999

A phase I trial of the pharmacokinetics, toxicity, and activity of KNI-272, an inhibitor of HIV-1 protease, in patients with AIDS or symptomatic HIV infection.

The pharmacokinetics, toxicity, and activity of KNI-272, a transition state inhibitor of HIV-1 protease, was assessed in a phase I trial. After an initial phase in which the pharmacokinetics were assessed, 37 patients with AIDS or symptomatic HIV infection and 100-400 CD4 cells/mm3 were entered in an escalating dose study. KNI-272 was administered four times daily for up to 12 weeks. Oral bioavailability ranged from 22 to 55% and was not appreciably different in the fasting and post-prandial state. The dose limiting toxicity was hepatic transaminase elevation; this could be reduced by escalating the dose over 4 weeks. When administered this way, the maximum tolerated oral dose was 40 mg/kg per day. At the highest two tolerated doses (26.4 and 40 mg/kg per day), there was some evidence of an anti-HIV effect with median decreases of 0.2-0.3 log10 copies/ml plasma HIV RNA; these decreases persisted through 7-8 weeks of treatment. There was an upward trend in the CD4 count at the 40 mg/kg per day dose but not at other doses. Additional studies focused on approaches to improve the therapeutic index of KNI-272 may be warranted.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Integrin alpha6beta1 plays a significant role in the attachment of hepatoma cells to laminin.

BACKGROUND/AIMS: Tumor invasion and metastasis consist of a series of complex events. During this process, the ability of tumor cells to adhere to laminin, a major component of basement membranes, is required at various steps. The expression of laminin-binding integrins and the extent of tumor metastasis and progression appear to be related. In hepatocellular carcinoma, increased expression of laminin-binding integrins is observed. However, little is known concerning the possible functional interactions between laminin-binding integrins and laminin. Therefore, we investigated the participation of laminin-binding integrins in the attachment of hepatoma cells to laminin. METHODS: Human hepatoma cell lines (KIM-1, KYN-1, 2) were used. We investigated the expression of integrin alpha1, alpha2, alpha3, alpha6, beta1, and beta4 subunits on hepatoma cells by immunocytochemical and flow cytometric analysis. Participation of these integrin subunits in the attachment of hepatoma cells to laminin was evaluated by an inhibition of cell adhesion assay. RESULTS: Integrin alpha1, alpha2, alpha3, alpha6 and beta1 subunits were expressed at the marginal areas of hepatoma cells, while the integrin beta4 subunit was scarcely detected. Laminin promoted the attachment of hepatoma cells in a dose-dependent manner. Although anti-integrin alpha1, alpha2, beta3 and beta4 subunit antibodies did not inhibit cell attachment to laminin, anti-integrin alpha6 and beta1 subunit antibodies inhibited the attachment by 50% or more. CONCLUSIONS: These findings indicate that integrin alpha6beta1 is very important in the attachment of hepatoma cells to laminin, suggesting the participation of this integrin in metastasis and invasion of hepatoma cells.

Carcinoma, Hepatocellular↗
PubMed1999

Levels of human defensin-1, an antimicrobial peptide, in saliva of patients with oral inflammation.

OBJECTIVE: The purpose of this study was to investigate the presence of an antimicrobial peptide, human defensin-1, in the saliva of patients with oral inflammation. STUDY DESIGN: Whole saliva samples were collected from patients with oral inflammation and from healthy volunteers. Human defensin-1 in saliva was isolated and purified by reversed-phase high-performance liquid chromatography. The amino acid sequence and molecular weight of defensin-1 were determined. The concentration of defensin-1 in saliva was quantified by high-performance liquid chromatography. Serum C-reactive protein concentration was measured by particle-enhanced turbidimetric immunoassay. RESULTS: The salivary defensin-1 concentration was significantly higher in patients with oral inflammation than in healthy volunteers; furthermore, in patients with oral inflammation, the concentration was significantly higher before treatment than after treatment. In the patients with oral inflammation, there was a strong positive correlation between salivary defensin-1 concentration and serum C-reactive protein concentration. CONCLUSIONS: The findings suggest that defensin-1 in saliva may be a convenient marker of inflammation associated with oral disease.

Adult↗
PubMed1999

Intragastric capsaicin stimulates motility of upper gut and proximal colon via distinct pathways in conscious dogs.

The aim of the present study was to investigate the effect and mechanism of action of intragastric and intraduodenal capsaicin on gastrointestinal motility. Five mongrel dogs were equipped with eight strain gauge force transducers on the stomach, small intestine, and proximal colon. In the interdigestive state, capsaicin was administered into the gastric or duodenal lumen. The effects of atropine, hexamethonium, ondansetron, and FK888 on capsaicin-induced contractions were studied. Intragastric capsaicin induced contractions within 15 min in the gastric antrum, duodenum, proximal jejunum, and proximal colon. These stimulatory effects were inhibited by atropine at all sites; by hexamethonium in the small intestine and colon; by ondansetron in the antrum, duodenum, and colon; and by FK888 in the antrum and colon, respectively. Intraduodenal capsaicin had no effect on contractility. Stimulation of afferent fibers by capsaicin in the stomach but not in the duodenum augments contractile activity in local and distant regions of the gut via distinct pathways.

Animals↗
PubMed1999

Serum hyaluronan as a predictor of hepatic regeneration after hepatectomy in humans.

BACKGROUND: The capacity for hepatic regeneration after hepatectomy is important for allowing surgeons to determine the appropriate extent of resection. However, conventional preoperative liver function tests are unsatisfactory for estimating the post-operative regenerative capacity of the remnant liver. The aim of this study was to evaluate the relationship between preoperative serum hyaluronan and hepatic regeneration. METHODS: Preoperative serum hyaluronan levels and the hepatic regeneration rate were estimated in 49 patients using computerized tomographic volumetry. The hepatic fibrotic rate was calculated with non-tumorous tissues stained with Azan-Mallory. Immunolocalization of factor VIII-related antigen (FVIIIAg) was examined as a marker for hepatic sinusoidal capillarization. RESULTS: The serum hyaluronan level was significantly correlated with the hepatic regeneration rate (P < 0. 001). Patients with serum hyaluronan levels below 200 ng mL-1 exhibited a significant correlation between the hepatic regeneration rate and the hepatic fibrotic rate. However, patients with serum hyaluronan levels above 200 ng mL-1 did not demonstrate a distinct correlation. The hepatic regeneration rate of patients with FVIIIAg in the liver and serum hyaluronan levels above 200 ng mL-1 were very low compared with those without FVIIIAg (P < 0.001). Multiple regression analysis revealed that serum hyaluronan was a significant predictor of post-operative hepatic regeneration among several clinical variables (r = 0.857, R2 = 0.735). CONCLUSION: It has been suggested that hepatic regeneration is closely related to both hepatic fibrosis and hepatic sinusoidal capillarization. The serum hyaluronan level is regarded as a useful predictor for hepatic regeneration after hepatectomy.

Adult↗
PubMed1999

Night-day-night sleep-wakefulness monitoring by ambulatory integrated circuit memories.

A medium-sized portable digital recorder with fully integrated circuit (IC) memories for sleep monitoring has been developed. It has five amplifiers for EEG, EMG, EOG, ECG, and a signal of body acceleration or respiration sound, four event markers, an 8 ch A/D converter, a digital signal processor (DSP), 192 Mbytes IC flash memories, and batteries. The whole system weighs 1200 g including batteries and is put into a small bag worn on the subject's waist or carried in their hand. The sampling rate for each input channel is programmable through the DSP. This apparatus is valuable for continuously monitoring the states of sleep-wakefulness over 24 h, making a night-day-night recording possible in a hospital, home, or car.

Ambulatory Care↗
PubMed1999

Experimental study of bone formation from autogenous periosteal graft following insulin-like growth factor I administration.

The present study evaluates the effect of insulin-like growth factor I (IGF-I) administration on bone formation following grafted periosteum. Twenty-four Japanese white rabbits were randomly assigned into one IGF-I administered group (1 mg for 14 days) and a second control group. Grafted periosteum taken from the tibia was placed under the submandibular muscles. At 14, 21, and 28 days following the operation, the grafted periosteum was extirpated and examined. Throughout all stages of the experiment, active bone formation was confirmed histologically and radiographically in both control and experimental groups. In addition, a micro-CT scan was used to observe three-dimensional micro structures in newly formed bone and to measure the trabecular bone thickness as a marker of bone development. As a result, a significant increase in bone formation in the IGF-I group was observed when compared with the findings in the control group. Trabecular bone thickness in the IGF-I group was significantly greater when compared with the control group at 14 days and 21 days following grafting (P < 0.01). At 28 days following grafting, there were no significant differences, suggesting that administration of IGF-I may play an important role in inducing bone formation from grafted periosteum in the early stages.

Animals↗
PubMed1999

Mutations in the NS5A gene predict response to interferon therapy in Japanese patients with chronic hepatitis C and cirrhosis.

The virus genotype, serum HCV-RNA level and liver histology are reported to be important factors in the response to interferon therapy. Recent studies have revealed that HCV NS5A 2209-2248 amino acid changes affect the response to interferon therapy of genotype 1b chronic hepatitis C. In contrast, some studies done in western countries have reported no such correlation. In the present study, interferon therapy was given to 58 Japanese patients, including 15 liver cirrhosis patients. NS5A 2209-2248 changes, the serum HCV level, ALT level, age and histology were examined in relation to the interferon effect. Twenty-four of the 58 patients (41%) showed a sustained virological response to the therapy. The responses to interferon therapy were significantly correlated with NS5A 2209-2248 changes (p < 0.0001), the HCV-RNA level (p < 0.0001) and histology (p < 0.0060). Among 15 liver cirrhosis patients, 3 of 6 mutant type patients showed a sustained virological response; 5 intermediate and 4 with wild type virus infected patients showed no responses. In conclusion, NS5A 2209-2248 changes may be a useful predictive marker of response to interferon therapy in addition to the serum HCV RNA level even in histologically advanced patients.

Adult↗
PubMed1999

In vivo distribution and behavior of paramagnetic dinitrosyl dithiolato iron complex in the abdomen of mouse.

It has been shown that a dinitrosyl dithiolato iron complex is formed under physiological conditions and that it functions as an NO transporter. In the present study, a diglutathionyl dinitrosyl iron complex [DNIC-(GS)2] was injected into mice and its abdominal distribution and behavior were examined by using electron paramagnetic resonance (EPR) spectroscopy. The X-band EPR signal intensity of the blood, liver, kidney, and spleen decreased with time but signals from the liver and kidney were readily detectable even 24h after the injection. The time courses of signal intensity were quite similar when the agent was administered via intravenous and subcutaneous injection routes, suggesting that DNIC-(GS)2 can penetrate readily and rapidly through the membranes. Real-time detection of DNIC-(GS)2 in the upper abdomen of the living mice was performed by employing an in vivo EPR spectroscopy. These results suggest that DNIC-(GS)2, an endogenous NO carrier, has an excellent membrane permeability and has a relatively high affinity for the liver and kidney.

Abdomen↗
PubMed1999

Apg7p/Cvt2p: A novel protein-activating enzyme essential for autophagy.

In the yeast Saccharomyces cerevisiae, the Apg12p-Apg5p conjugating system is essential for autophagy. Apg7p is required for the conjugation reaction, because Apg12p is unable to form a conjugate with Apg5p in the apg7/cvt2 mutant. Apg7p shows a significant similarity to a ubiquitin-activating enzyme, Uba1p. In this article, we investigated the function of Apg7p as an Apg12p-activating enzyme. Hemagglutinin-tagged Apg12p was coimmunoprecipitated with c-myc-tagged Apg7p. A two-hybrid experiment confirmed the interaction. The coimmunoprecipitation was sensitive to a thiol-reducing reagent. Furthermore, a thioester conjugate of Apg7p was detected in a lysate of cells overexpressing both Apg7p and Apg12p. These results indicated that Apg12p interacts with Apg7p via a thioester bond. Mutational analyses of Apg7p suggested that Cys507 of Apg7p is an active site cysteine and that both the ATP-binding domain and the cysteine residue are essential for the conjugation of Apg7p with Apg12p to form the Apg12p-Apg5p conjugate. Cells expressing mutant Apg7ps, Apg7pG333A, or Apg7pC507A showed defects in autophagy and cytoplasm-to-vacuole targeting of aminopeptidase I. These results indicated that Apg7p functions as a novel protein-activating enzyme necessary for Apg12p-Apg5p conjugation.

Adenosine Triphosphate↗
PubMed1999

Significance of membrane type 1 matrix metalloproteinase expression in breast cancer.

Expression of matrix metalloproteinases (MMPs) plays an essential role in tumor metastasis and invasion through the degradation of extracellular matrix (ECM). MT1-MMP (membrane type 1 matrix metalloproteinase), a membrane-type MMP, is responsible for the activation of MMP2. In this study the significance of MT1-MMP expression in human breast tumors was investigated by immunocytochemical assay, and its correlation with clinicobiological features was analyzed. MT1-MMP expression was detected in tumor cells and/or stromal cells, and there was a strong correlation between the expressions of MT1-MMP in the two cell types. Out of 183 primary tumors, 103 (56.2%) showed positive staining of MT1-MMP in tumor cells. MT1-MMP expression showed no significant correlation with any of the clinicobiological parameters examined, including hormone receptor status and angiogenesis. In postoperative survival analysis, MT1-MMP expression itself was not a significant prognostic factor. However, in the particular subgroup with the accumulation of thymidine phosphorylase (TP)-positive stromal cells, which have been activated by various stimuli, such as cytokines and hypoxia, MT1-MMP expression had a significant prognostic value. These data suggested that MT1-MMP might function cooperatively with tumor-associated stromal cells for the progression of breast cancer.

Breast Neoplasms↗
PubMed1999

Defensin-1, an antimicrobial peptide present in the saliva of patients with oral diseases.

OBJECTIVES AND DESIGN: A preceding paper has noted a detection of defensin-1 (HNP-1), a peptide with antimicrobial and cytotoxic properties, in the saliva of patients with oral squamous cell carcinoma. The present study deals with the presence of HNP-1 in the saliva of patients with various oral diseases. METHODS: Whole saliva samples were obtained from the patients. HNP-1 in the saliva was isolated and purified by HPLC and the amino acid sequence of the peptide was determined. The molecular weight of HNP-1 was measured by mass spectrometry. The concentration of HNP-1 in saliva was determined by comparing the height of eluted HNP-1 with that of a synthetic HNP-1 standard. RESULTS: The concentrations of HNP-1 in the saliva of patients with oral lichen planus (n = 5), leukoplakia (n = 4), and glossitis associated with iron deficiency (n = 4) were 8.3 +/- 4.3 micrograms ml-1, 13.2 +/- 7.9 micrograms ml-1, and 11.4 +/- 4.9 micrograms ml-1, (mean +/- s.d.), respectively. These concentrations were significantly higher than those in healthy subjects (0.8 microgram ml-1) (P < 0.01). In contrast, salivary HNP-1 concentrations in patients with glossodynia (n = 4) and oral discomfort (n = 4) were similar to those in healthy subjects. CONCLUSIONS: Since HNP-1 is a non-specific defensive peptide present in neutrophils, it may play an important role in the protection against diseases such as oral lichen planus, leukoplakia, and glossitis associated with iron deficiency.

Adult↗
PubMed1999

Acute cerebellar ataxia with human parvovirus B19 infection.

A 2 year old boy developed acute cerebellar ataxia in association with erythema infectiosum. During the disease, genomic DNA and antibodies against human parvovirus B19 were detected in serum but not in cerebrospinal fluid. Parvovirus B19 associated acute cerebellar ataxia might occur due to transient vascular reaction in the cerebellum during infection.

Acute Disease↗
PubMed1999

Motor dynamics encoding in cat cerebellar flocculus middle zone during optokinetic eye movements.

We investigated the relationship between eye movement and simple-spike (SS) frequency of Purkinje cells in the cerebellar flocculus middle zone during the optokinetic response (OKR) in alert cats. The OKR was elicited by a sequence of a constant-speed visual pattern movement in one direction for 1 s and then in the opposite direction for 1 s. Quick-phase-free trials were selected. Sixty-six cells had direction-selective complex spike (CS) activity that was modulated during horizontal (preferring contraversive) but not vertical stimuli. The SS activity was modulated during horizontal OKR, preferring ipsiversive stimuli. Forty-one cells had well-modulated activity and were suitable for the regression model. In these cells, an inverse dynamics approach was applied, and the time course of the SS rate was reconstructed, with mean coefficient of determination 0.76, by a linear weighted superposition of the eye acceleration (mean coefficient, 0.056 spikes/s per deg/s(2)), velocity (5.10 spikes/s per deg/s), position (-2.40 spikes/s per deg), and constant (mean 34.3 spikes/s) terms, using a time delay (mean 11 ms) from the unit response to the eye response. The velocity and acceleration terms contributed to the increase in the reconstructed SS rates during ipsilateral movements, whereas the position term contributed during contralateral movements. The standard regression coefficient analyses revealed that the contribution of the velocity term (mean coefficient 0.81) was predominant over the acceleration (0.03) and position (-0.17) terms. Forward selection analysis revealed three cell types: Velocity-Position-Acceleration type (n = 27): velocity, position, and acceleration terms are significant (P < 0.05); Velocity-Position type (n = 12): velocity and position terms are significant; and Velocity-Acceleration type (n = 2): velocity and acceleration terms are significant. Using the set of coefficients obtained by regression of the response to a 5 deg/s stimulus velocity, the SS rates during higher (10, 20, and 40 deg/s) stimulus velocities were successfully reconstructed, suggesting generality of the model. The eye-position information encoded in the SS firing during the OKR was relative but not absolute in the sense that the magnitude of the position shift from the initial eye position (0 deg/s velocity) contributed to firing rate changes, but the initial eye position did not. It is concluded that 1) the SS firing frequency in the cat middle zone encodes the velocity and acceleration information for counteracting the viscosity and inertia forces respectively, during short-duration horizontal OKR and 2) the apparent position information encoded in the SS firing is not appropriate for counteracting the elastic force during the OKR.

Animals↗
PubMed1999

Adhesive interaction between P-selectin and sialyl Lewis(x) plays an important role in recurrent coronary arterial thrombosis in dogs.

Cell adhesion molecules may play an important role in the disease process of acute coronary syndromes. We have shown a neutralizing anti-P-selectin monoclonal antibody and a sialyl Lewis(x)-containing oligosaccharide (SLe(x)-OS), an analogue of selectin ligand on leukocytes, reduce cyclic flow variations (CFVs) in a canine model of recurrent coronary arterial thrombosis, suggesting the important interaction between P-selectin and SLex for the pathophysiology of these syndromes. However, the functional role of these adhesion molecules in the thrombotic process remains unclear. Therefore, we investigated effects of SLe(x)-OS on CFVs, platelet P-selectin expression, and morphology of the stenotic site in the same model. Anesthetized open-chest dogs (n=34) were randomly divided into 4 groups after developing CFVs. Dogs intravenously received saline or graded doses of SLe(x)-OS (5, 20, or 40 mg/kg bolus) infusion followed by a continuous infusion (5 mg. kg-1. h-1) for 60 minutes. By flow cytometric analysis, P-selectin expression on platelets after CFVs was significantly upregulated during CFVs. Immunohistochemical analysis revealed the incorporation of platelets with upregulated P-selectin within thrombi at the stenotic site. Microscopic observations revealed the presence of numerous platelets adhered to leukocytes at the stenotic site on the damaged endothelium. SLe(x)-OS significantly reduced CFVs, inhibited the P-selectin expression on platelets, and prevented the adherence of platelets and leukocytes. These findings further support the notion that the adhesive interaction between P-selectin on platelets and SLe(x) on leukocytes plays an important role in platelet-mediated thrombus formation in this model.

Animals↗