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Biomedical subjects

T Ueno

Publications and source records attributed to T Ueno.

At least 235 records · Page 13Linked to original sources

Development of a noninvasive technique for the measurement of intracranial pressure.

Intracranial pressure (ICP) dynamics are important for understanding adjustments to altered gravity. Previous flight observations document significant facial edema during exposure to microgravity, which suggests that ICP is elevated during microgravity. However, there are no experimental results obtained during space flight, primarily due to the invasiveness of currently available techniques. We have developed and refined a noninvasive technique to measure intracranial pressure noninvasively. The technique is based upon detecting skull movements of a few micrometers in association with altered intracranial pressure. We reported that the PPLL technique has enough sensitivity to detect changes in cranial distance associated with the pulsation of ICP in cadavera. In normal operations, however, we place a transducer on the scalp. Thus, we cannot rule out the possibility that the PPLL technique picks up cutaneous pulsation. The purpose of the present study was therefore to show that the PPLL technique has enough sensitivity to detect changes in cranial distance associated with cardiac cycles in vivo.

Blood Pressure↗

Mobility of the obturator prosthesis in hemimaxillectomy edentulous patients.

In edentulous patients with maxillary defects, it is difficult to obtain sufficient retention, support, and stability of the obturator prosthesis, in addition, its mobility during various functions is considered to be large. A thorough understanding of the mobility of the obturator prosthesis is important to achieve successful results in the patient's oral rehabilitation. In this study, the ranges of movement of the obturator prostheses in three hemimaxillectomy edentulous patients were compared during tapping, chewing (biscuit), and opening and clenching jaw movements by simultaneously conducting three-dimensional measurements of three points that were established on the central incisor and the right and left first molars of the obturator prosthesis with a jaw movement tracking device having six degrees of freedom. This study indicates that the range of movement of the obturator prosthesis varied extensively from individual to individual. The ranges of movement were larger than those of normal complete dentures and differed considerably from each other when categorized according to the three functions and three measuring points in the patients.

Aged↗

Effect of teeth clenching on isometric and isokinetic strength of ankle plantar flexion.

To investigate the effect of voluntary teeth clenching on the isometric and isokinetic exercises of the lower limbs, the association of muscle strength (peak torque, PT) and muscle activities (integrated electromyographic activity per unit of time, iEMG/s) of the three muscles of the triceps surae with teeth clenching during isometric and isokinetic plantar flexion were simultaneously measured for 12 healthy male volunteers using a Cybex 6000 Extremity Testing and Rehabilitation System and a surface EMG analyzing system. The statistical analysis demonstrated that for the isometric exercise, PT and each iEMG/s significantly increased in association with teeth clenching, and a positive correlation existed between the biting force and each variable. In contrast, no association was found with teeth clenching for the isokinetic exercise. In this study, therefore, it was found that the effect of teeth clenching differed between the isometric and isokinetic exercises.

Adult↗

Homogeneous assay for measuring low-density lipoprotein cholesterol in serum with triblock copolymer and alpha-cyclodextrin sulfate.

We have developed a fully automated method for measuring LDL-cholesterol (LDL-C) in human serum without the need for prior separation, using a nonionic surfactant, polyoxyethylene-polyoxypropylene block copolyether (POE-POP), and a sodium salt of sulfated cyclic maltohexaose, alpha-cyclodextrin sulfate. Of the surfactants tested, POE-POP with a higher molecular mass of the POP block and a greater hydrophobicity reduced the reactivity of cholesterol in lipoprotein fractions; the reactivity in descending order was LDL >> VLDL > chylomicron approximately HDL. Gel filtration chromatographic studies revealed that POE-POP removed lipids selectively from the LDL fraction and allowed them to participate in the cholesterol esterase-cholesterol oxidase coupling reaction system. By contrast, alpha-cyclodextrin sulfate reduced the reactivity of cholesterol, especially in chylomicrons and VLDL. A combination of POE-POP with alpha-cyclodextrin sulfate provided the required selectivity for the determination of LDL-C in serum in the presence of magnesium ions and a small amount of dextran sulfate without precipitating lipoprotein aggregates. There was a good correlation between the results of LDL-C assayed by the proposed method and the beta-quantification reference method involving 161 sera with triglyceride concentrations ranging from 0.3 to 22.6 mmol/L.

Automation↗

Significance of circulating hepatocyte growth factor level as a prognostic indicator in primary breast cancer.

The circulating hepatocyte growth factor (HGF)/scatter factor level is frequently increased in advanced cancer patients. In this study, we have assessed the prognostic value of the circulating HGF level determined by enzymatic immunoassay in primary breast cancer patients. Of 200 primary breast cancer patients, 54 (27.0%) showed the increase of serum HGF level according to the age-matched cutoff values. The prognosis of the patients with the increased HGF level was statistically worse than that of the patients with normal HGF level (P = 0.0001, log-rank test). Multivariate analysis confirmed that the increase in HGF level was an independent prognostic indicator in primary breast cancer patients. In the background analysis, the increase in serum HGF level was significantly associated with tumor size, nodal status, and histological evidence of venous invasion. The data indicate that up-regulation of the circulating HGF level may predict systemic tumor spread and early relapse in primary breast cancer patients.

Adult↗

[A case report: inhaled nitric oxide improves respiratory function in an infant with pulmonary hypertension].

Nitric oxide (NO) was administered to an infant in a near fatal crisis of pulmonary hypertension after total correction of double outlet right ventricle. Inhaled NO of 4 parts per million reduced pulmonary arterial pressure (PAP) and increased tidal volume during pressure limit ventilation. Both respiratory system compliance and resistance were improved with NO inhalation. There was a significant negative correlation between mean PAP and respiratory system compliance. We speculated that a reduction in PAP with NO inhalation resulted in the improvement of respiratory function. He was successfully weaned from mechanical ventilation.

Double Outlet Right Ventricle↗

[Development of anti-cancer drugs under new renewed GCP--from the viewpoint of drug development company developer].

During the past 7 years since the enforcement of Japan's first GCP in October 1990, various standards and guidelines have been introduced in Japan. On the other hand, the harmonization of GCP has been the subject of major discussion at ICH in order to allow the mutual acceptance of clinical data from different countries. In order to further improve the reliability and consistency of clinical data and the ethics of clinical trials in Japan, the new GCP was enforced in April 1997. A clinical study is conducted by the sponsor, but will only be successful with the collaboration of trial subjects, medical institutions, heads of medical institutions, investigators, subinvestigators, pharmacists, nurses, laboratory technicians, and other assisting staff. Before the full enforcement of the new GCP, we, as sponsors of clinical trials, carried out a survey of the current status of clinical trials centering on the reactions of medical institutions to the new GCP, future of clinical trials on anti-cancer drugs in Japan, and differences in time from clinical trials to registration in Japan, the United State and Europe. We sent a questionnaire by facsimile to 21 pharmaceutical companies which have developed or are developing anti-cancer drugs and obtained replies from 20 companies (95%) from August 25 to 30, 1997. This paper reports issues concerning clinical trials on anti-cancer drugs based on the results of our survey.

Antineoplastic Agents↗

Comparative enzymatic study of HIV-1 reverse transcriptase resistant to 2',3'-dideoxynucleotide analogs using the single-nucleotide incorporation assay.

Employing the single-nucleotide incorporation assay using a heteropolymeric RNA template and DNA primers, we defined enzymatic profiles of recombinant human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) containing a set of five mutations [A62V, V75I, F77L, F116Y, and Q151M] which confers resistance to multiple 2',3'-dideoxynucleosides (ddNs) on HIV-1. RTs containing other drug-resistance-associated mutations were also examined. The K(m) for dNTPs, the kcat, and the kcat/ K(m) ratios of mutant RTs were all comparable to those of wild-type RT (RTwt). The processive primer extension activity of mutant RTs was also comparable to that of RTwt as examined in the presence of saturating concentrations of dNTPs and heparin. Determination of the Ki values toward 5'-triphosphates (TP) of various ddNs [3'-azido-2',3'-dideoxythymidine (AZT), 2',3'-didehydro-2',3'-dideoxythymidine (D4T), 2',3'-dideoxycytidine (ddC), (-)-beta-L-2',3'-dideoxy-3'-thiacytidine (3TC), (-)-beta-L-2',3'-dideoxy-5-fluorocytidine (FddC), 2',3'-dideoxyadenosine (ddA), and 2'-beta-fluoro-2',3'-dideoxyadenosine (FddA)] and 9-(2-phosphonylmethoxyethyl)adenine diphosphate (PMEApp) revealed that RTA62V/V75I/F77L/F116Y/Q151M was insensitive to ddATP, AZTTP, D4TTP, FddATP, and ddCTP, but was sensitive to PMEApp, 3TCTP, and FddCTP. RTK65R was less sensitive to ddATP, FddATP, PMEApp, ddCTP, and 3TCTP, while RTM184V was less sensitive only to 3TCTP and ddCTP. The determination of Ki(ddNTP)/K(m)(dNTP) ratios showed that AZTTP, D4TTP, and ddCTP are, as substrates, as efficient for RTwt as their corresponding dNTPs, that ddATP, PMEApp, and 3TCTP are moderately efficient substrates for RTwt, and that FddATP is the least efficient substrate among ddNTPs examined. The observed cross-resistance of HIV-1 RT to various ddNTPs should reflect the alteration of RT's substrate recognition and should provide insights into the molecular mechanism of RT discrimination of ddNTPs from natural substrates.

Anti-HIV Agents↗

Vasospastic angina induced by nonsteroidal anti-inflammatory drugs.

We report two cases of vasospastic angina associated with anaphylactic reaction caused by nonsteroidal anti-inflammatory drugs (NSAIDs). Both patients exhibited anaphylactic manifestations, such as general rash and urticaria, along with angina pectoris with electrocardiographic ST-segment elevations after suppository administration of diclofenac sodium or indomethacin, the most commonly used NSAIDs. Although these patients had normal coronary arteriograms, intracoronary administration of ergonovine or acetylcholine provoked diffuse coronary artery spasms accompanied by chest pain and ischemic ST-segment changes. It is therefore suggested that an allergic mechanism may be involved as a causative factor of the coronary artery spasm induced by NSAIDs.

Aged↗

Relaxing effect of interleukin-1 on rat cultured Ito cells.

Interleukin-1beta (IL-1beta) is closely involved in liver disorders. IL-1beta produces nitric oxide (NO) in vascular smooth muscle cells and relaxes vascular smooth muscle via cyclic guanosine 3',5'-monophosphate (cGMP). In this study, we evaluated the relaxing effect of IL-1beta on cultured Ito cells. Ito cells were isolated from the livers of male Wistar rats and cultured for 24 hours. Immunolocalization of inducible nitric oxide synthase (iNOS) and cGMP and intensity of fluorescence of cGMP were examined using a confocal laser microscope. Ito cells were treated with 0, 200, and 1,000 pmol/L IL-1beta, and the intracellular cGMP concentration was measured after 12 hours. Moreover, Ito cells treated with 200 and 1,000 pmol/L IL-1beta and not treated with IL-1beta were observed over 12 hours, and the area of the same Ito cell was compared before and after the addition of IL-1beta. Next, effects of N(G)-monomethyl-L-arginine (L-NMMA) and S-nitroso-N-acetyl-DL-penicillamine (SNAP) on Ito cell relaxation by IL-1beta treatment were examined. In Ito cells, immunofluorescence of iNOS was observed, and fluorescent intensity of cGMP increased after addition of IL-1beta. Intracellular cGMP concentration increased dose-dependently after addition of IL-1beta. Cell area significantly increased in the IL-1beta-treated group compared with the untreated group. Relaxation of Ito cells by IL-1beta treatment was inhibited by L-NMMA in a dose-dependent manner, but was enhanced by SNAP. These results indicate that IL-1beta produces NO in cultured Ito cells and relaxes the cells via cGMP.

Animals↗

Molting hormonal and larvicidal activities of aliphatic acyl analogs of dibenzoylhydrazine insecticides.

Dibenzoylhydrazines are the nonsteroidal ecdysone agonists. Using comparative molecular field analysis, we previously found that the alkyl side chain of 20-hydroxyecdysone (20E) is three-dimensionally superposable with one of their two aryl moieties. To identify the aryl moiety that is better superposable on the alkyl chain, we synthesized compounds in which one of the two aryl groups of tebufenozide (N-t-butyl-N-3,5-dimethylbenzoyl-N'-4-ethylbenzoylhydrazine) is replaced by alkyl groups such as C4H9, C5H11, and C6H13. The molting hormonal activity of these compounds was measured using cultured integuments prepared from rice stem borers, Chilo suppressalis Walker, in terms of stimulation of incorporation of N-acetyl-[14C]glucosamine. N-t-Butyl-N-3,5-dimethylbenzoyl-N'-acylhydrazines with a hexanoyl or heptanoyl group were about 20-fold higher than that of 20E, whereas N-acyl-N-t-butyl-N'-4-ethylbenzoylhydrazines with a hexanoyl or heptanoyl group were much weaker than 20E. Their larvicidal activity was also measured against rice stem borers. The former series of compounds were much more active than the other series as well as 20E. Thus, the benzoyl moiety of dibenzoylhydrazines, which is bound to the secondary nitrogen atom (-NH-), is replaceable by aliphatic acyl groups without greatly affecting the biological activities.

Acylation↗

Hepatic stellate cells and intralobular innervation in human liver cirrhosis.

In normal and cirrhotic human liver tissues, we examined immunolocalization of alpha-smooth muscle actin (alpha-SMA), endothelin-1 receptor (ET-1R), and S-100 protein, with special emphasis on the intralobular spaces, using immunohistochemical methods. The ratio of the number of hepatic stellate cells (HSCs) with closely apposing nerve endings to the total number of HSCs in normal livers was compared with that in cirrhotic livers by electron microscopy. Immunolocalization of alpha-SMA and ET-1R was obviously recognized along the sinusoidal walls in cirrhotic liver and was significantly increased in cirrhotic liver compared with that in normal liver. Immunoreactive products for these substances were mainly localized in HSCs. However, immunolocalization of S-100 protein in intralobular spaces was markedly decreased in cirrhotic liver compared with that in normal liver. Nerve fibers were ultrastructurally hardly visible in intralobular spaces of cirrhotic livers. The ratio of the number of HSCs with closely apposing nerve endings to the total number of HSCs was significantly reduced in cirrhotic liver compared with that in normal liver. These results indicate that in liver cirrhosis, alpha-SMA-positive HSCs may play an important role in hepatic sinusoidal microcirculation through vasoactive agents such as ET-1 rather than through intralobular innervation.

Actins↗

Coordinated expression of integrin alpha6beta1 and laminin in hepatocellular carcinoma.

The interaction between tumor cells and laminin mediated by laminin-binding integrins is critical for tumor invasion and metastasis. The aim of this study was to clarify the altered expression of laminin-binding integrins with the change of laminin deposition in hepatocellular carcinoma (HCC) in comparison with cirrhotic or normal liver by immunohistochemistry. In HCC, hepatoma cells and sinusoidal endothelial cells expressed integrins alpha1beta1, alpha2beta1, alpha3beta1, and alpha6beta1. Integrins alpha1beta1 and alpha6beta1 were detected in a continuous pattern along the sinusoids in accordance with laminin assembly. Integrins alpha2beta1 and alpha3beta1 were detected in a discontinuous pattern at these sites. Integrin alpha6beta4 was not detected. In cirrhotic liver, although integrins alpha1beta1 and alpha6beta1 as well as laminin were detected in a continuous pattern along the sinusoids, integrins alpha2beta1, alpha3beta1, and alpha6beta4 were not detected. In normal liver, although integrin alpha1beta1 was detected in a continuous pattern along the sinusoids, neither integrins alpha2beta1, alpha3beta1, alpha6beta1, alpha6beta4, nor laminin were detected. We have clarified that, of laminin-binding integrins, the localization of integrin alpha6beta1 shows the best correspondence with the localization of laminin. These results suggest that of laminin-binding integrins, integrin alpha6beta1 is very important for cell-laminin interactions in HCC.

Adult↗

Basic fibroblast growth factor regulates proliferation and motility of human hepatoma cells by an autocrine mechanism.

BACKGROUND/AIMS: Basic fibroblast growth factor has mitogenic and angiogenic properties. In this study, we aimed to evaluate the role of fibroblast growth factor in the development and progression of human hepatocellular carcinoma. METHODS: The expression of basic fibroblast growth factor, fibroblast growth factor receptor-1, and a receptor isoform was investigated by in situ hybridization, immunohistochemistry, reverse transcription-polymerase chain reaction, Western blot analysis and confocal laser-scanning microscopy. The influence of exogenous basic fibroblast growth factor on DNA synthesis and motility of human hepatoma cells were also evaluated. RESULTS: Basic fibroblast growth factor and fibroblast growth factor receptor-1 messenger RNAs were present mainly in tumor cells and less so in hepatocytes from noncancerous liver tissue. Immunoreactive products of basic fibroblast growth factor and fibroblast growth factor receptor-1 were observed in tumor cells. The isoform IIIc was expressed in hepatocellular carcinoma tissue and hepatoma cell lines. Exogenous basic fibroblast growth factor stimulated DNA synthesis and motility of hepatoma cells. The effect was more marked in poorly-differentiated hepatoma cells than in well-differentiated hepatoma cells. Fibroblast growth factor-1 expression on hepatoma cells was also more marked in poorly-differentiated hepatoma cells than in well-differentiated hepatoma cells. The stimulated motility on basic fibroblast growth factor was suppressed by an anti-fibroblast growth factor receptor-1 antibody. CONCLUSIONS: Basic fibroblast growth factor may play an important role in the development and progression of hepatocellular carcinoma via an autocrine mechanism involving fibroblast growth factor and its receptor.

Adult↗