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M Uemura

Publications and source records attributed to M Uemura.

At least 19 recordsLinked to original sources
PubMed2011

Overexpression of ribosomal RNA in prostate cancer is common but not linked to rDNA promoter hypomethylation.

Alterations in nucleoli, including increased numbers, increased size, altered architecture and increased function are hallmarks of prostate cancer cells. The mechanisms that result in increased nucleolar size, number and function in prostate cancer have not been fully elucidated. The nucleolus is formed around repeats of a transcriptional unit encoding a 45S ribosomal RNA (rRNA) precursor that is then processed to yield the mature 18S, 5.8S and 28S RNA species. Although it has been generally accepted that tumor cells overexpress rRNA species, this has not been examined in clinical prostate cancer. We find that indeed levels of the 45S rRNA, 28S, 18S and 5.8S are overexpressed in the majority of human primary prostate cancer specimens as compared with matched benign tissues. One mechanism that can alter nucleolar function and structure in cancer cells is hypomethylation of CpG dinucleotides of the upstream rDNA promoter region. However, this mechanism has not been examined in prostate cancer. To determine whether rRNA overexpression could be explained by hypomethylation of these CpG sites, we also evaluated the DNA methylation status of the rDNA promoter in prostate cancer cell lines and the clinical specimens. Bisulfite sequencing of genomic DNA revealed two roughly equal populations of loci in cell lines consisting of those that contained densely methylated deoxycytidine residues within CpGs and those that were largely unmethylated. All clinical specimens also contained two populations with no marked changes in methylation of this region in cancer as compared with normal. We recently reported that MYC can regulate rRNA levels in human prostate cancer; here we show that MYC mRNA levels are correlated with 45S, 18S and 5.8S rRNA levels. Further, as a surrogate for nucleolar size and number, we examined the expression of fibrillarin, which did not correlate with rRNA levels. We conclude that rRNA levels are increased in human prostate cancer, but that hypomethylation of the rDNA promoter does not explain this increase, nor does hypomethylation explain alterations in nucleolar number and structure in prostate cancer cells. Rather, rRNA levels and nucleolar size and number relate more closely to MYC overexpression.

Adult↗
PubMed2006

Increased ADAMTS-13 proteolytic activity in rat hepatic stellate cells upon activation in vitro and in vivo.

INTRODUCTION: ADAMTS-13 is a member of A Disintegrin And Metalloprotease with ThromboSpondin type 1 repeats (ADAMTS) family, primarily synthesized in hepatic stellate cells (HSCs), one of the major cell types transdifferentiating into myofibroblasts during liver fibrosis. However, the association between ADAMTS-13 expression and HSC activation or liver fibrosis is not known. METHODS: In this study, we determined the ADAMTS-13 mRNA, protein, and activity in isolated primary HSCs upon activation on a plastic dish and in liver after administration of carbon tetrachloride (CCl(4)) in rats. RESULTS: We showed that ADAMTS-13 antigen and proteolytic activity in the activated rat HSCs were dramatically increased, whereas ADAMTS-13 mRNA in these cells was only minimally altered. Similarly, the ADAMTS-13 antigen and proteolytic activity in rat liver after CCl(4) injury were also significantly increased, whereas the ADAMTS-13 mRNAs in these liver tissues were only slightly increased compared with normal. Surprisingly, despite the dramatic up-regulation of ADAMTS-13 protein synthesis in the activated HSCs after CCl(4) administration, the plasma levels of ADAMTS-13 protease in rats did not increase concordantly. CONCLUSION: We conclude that the up-regulation of ADAMTS-13 protein expression in rat HSCs during activation in vitro and in vivo suggests the possibility of ADAMTS-13 proteolysis, an important part of function of the activated HSCs, perhaps through modulation of liver regeneration or formation of liver fibrosis after various injuries. The data also suggest the minimal contribution of the activated HSCs in regulation of plasma levels of ADAMTS-13 protease.

ADAM Proteins↗
PubMed2005

Psychophysical analysis of monitor display functions affecting observer diagnostic performance of CT image on liquid crystal display monitors.

The aim of the present study was to propose suitable display functions for CT image representation on liquid crystal display (LCD) monitors by analyzing the characteristics of the monitor's typical display functions using psychophysical analysis. The luminance of the LCD monitor was adjusted to a maximum of 275 cd/m2 and 480 cd/m2. Three types of postcalibrated display functions (i.e., GSDF, CIELAB, and Exponential gamma 2.2) were evaluated. Luminance calculation of a new grayscale test pattern (NGTP) was done for the conversion of the digital driving level (DDL) into the CT value. The psychophysical gradient delta of display functions for the CT value was evaluated and compared via statistical analysis. The delta value of GSDF and CIE decreased exponentially; however, the delta value of Exponential gamma 2.2 showed a convex curve with a peak at a specific point. There was a statistically significant difference among the delta values of the three types of display functions on the 480 cd/m2 maximum via Kruskal Wallis test (P<0.001). The GSDF was suitable for observation of abdominal and lung CT images; however, the display function combined the Exponential gamma 2.2 and the GSDF functions and was ideal for observation of brain CT images by psychophysical analysis.

Brain↗
PubMed2005

Angiopoietin 2 displays a vascular endothelial growth factor dependent synergistic effect in hepatocellular carcinoma development in mice.

BACKGROUND: Orchestration of two major classes of angiogenic factors-namely, vascular endothelial growth factor (VEGF) and angiopoietin 2 (Ang-2)-has been shown to play a pivotal role in tumour angiogenesis, including hepatocellular carcinoma (HCC). However, few studies have focused on the direct interaction of these factors on in vivo tumour development and angiogenesis. AIM: To examine the interaction between both factors in murine HCC. METHODS: We examined the combination effect of VEGF and Ang-2 overexpression by means of a combination of a retroviral tetracycline (tet) regulated gene manipulating system in vivo, by providing tet in the drinking water, and a conventional plasmid gene expression system. RESULTS: Neither Ang-2 nor VEGF overexpression induced proliferation of HCC cells in vitro. In vivo, although overexpression of Ang-2 did not increase tumour development, simultaneous expression of Ang-2 and VEGF synergistically augmented tumour growth and angiogenesis in murine HCC. Ang-2 plus VEGF induced tumour development was markedly attenuated by treatment with neutralising monoclonal antibodies against VEGF receptors. Ang-2 plus VEGF overexpression significantly increased the activities of matrix metalloproteinase (MMP)-2 and MMP-9 in the tumour. Suppression of intratumoral VEGF almost completely abolished this augmentation of MMPs. CONCLUSIONS: These results suggest that Ang-2 synergistically augments VEGF mediated HCC development and angiogenesis. This proangiogenic activity was exerted only in the presence of VEGF, at least partly mediated via induction of MMP-2 and MMP-9 in the tumour.

Angiopoietin-2↗
PubMed2005

Evaluation of grey-scale standard display function as a calibration tool for diagnostic liquid crystal display monitors using psychophysical analysis.

The digital imaging and communications in medicine (DICOM) standard proposed the grey-scale standard display function (GSDF) as a calibration tool for making the gradation characteristic of a radiographic output image consistent. This is designed in such a manner that the contrast visually recognised by observers (called psychophysical contrast) becomes a constant for all digital driving levels. The DICOM standard calls such an ideal characteristic perceptual linearisation. The psychophysical gradient that can express the psychophysical contrast was introduced for the evaluation of the GSDF using a liquid crystal display monitor. Investigations regarding its ability to yield a constant psychophysical contrast, independent of the digital driving level change and under an actual observation environment, such as for clinical radiographic diagnosis in hospital, were carried out. The psychophysical gradients of the GSDF were obtained for two kinds of observation environment: one was a restricted environment such as in a dark room, under steady-state adaptation, using the sinusoidal grading pattern corresponding to the peak frequency of the human eye response. The other was an actual environment reflecting that encountered during clinical diagnosis in a hospital. As a result, the psychophysical gradient under the restricted environment became almost constant and independent of the change in digital driving level, i.e. perceptual linearisation could be satisfied. Furthermore, under the actual observation environment, the psychophysical gradient decreased gradually with the increase in digital driving level, i.e. the perceptual linearisation could not be satisfied. The percentage decrease in the value of the psychophysical gradient at the maximum luminance area was approximately 60% compared with that at the minimum luminance area. Accordingly, the GSDF is unsuitable as a calibration tool for the liquid crystal display monitor, which will be used in actual clinical diagnosis, as it cannot achieve 'perceptual linearisation' under the actual environment. For the purpose of clinical diagnosis, it is necessary to enlarge the physical gradient of GSDF further in the high digital driving level range (which relates to a high luminance area) to give an approximation that is as close to the idealised form as possible.

Calibration↗
PubMed2004

Proteomics of the rice cell: systematic identification of the protein populations in subcellular compartments.

Despite recent progress in sequencing the complete genome of rice ( Oryza sativa), the proteome of this species remains poorly understood. To extend our knowledge of the rice proteome, the subcellular compartments, which include plasma membranes (PM), vacuolar membranes (VM), Golgi membranes (GM), mitochondria (MT), and chloroplasts (CP), were purified from rice seedlings and cultured suspension cells. The proteins of each of these compartments were then systematically analyzed using two-dimensional (2D) electrophoresis, mass spectrometry, and Edman sequencing, followed by database searching. In all, 58 of the 464 spots detected by 2D electrophoresis in PM, 43 of the 141 spots in VM, 46 of the 361 spots in GM, 146 in the 672 spots in MT, and 89 of the 252 spots in CP could be identified by this procedure. The characterized proteins were found to be involved in various processes, such as respiration and the citric acid cycle in MT; photosynthesis and ATP synthesis in CP; and antifungal defense and signal systems in the membranes. Edman degradation revealed that 60-98% of N-terminal sequences were blocked, and the ratios of blocked to unblocked proteins in the proteomes of the various subcellular compartments differed. The data on the proteomes of subcellular compartments in rice will be valuable for resolving questions in functional genomics as well as for genome-wide exploration of plant function.

Cell Membrane↗
PubMed2004

Development and evaluation of a new gray-scale test pattern to adjust gradients of thoracic CT imaging.

The purpose of the present study was to evaluate the usefulness of a new gray-scale test pattern (NGTP) that was developed to easily adjust the gradients of thoracic CT imaging and enable visual consistency. The Society of Motion Picture and Television Engineers (SMPTE) pattern and the NGTP were used for comparison. The luminance character of two test patterns was evaluated by a luminance meter with three different window widths and levels (for default, mediastinum and lung). We also investigated whether SMPTE or NGTP is more suitable for adjusting the gradient of thoracic CT imaging. We found that it was easier to adjust the gradient of thoracic CT imaging with NGTP than with SMPTE, because the digital range of NGTP is 12 bits (the value of 4,096 HU, from -1,024 to 3,071 HU), and adjustable in any window width. We were able to adjust the gradients of hard-copy and soft-copy thoracic CT imaging within several hours using NGTP. We propose that NGTP is the most suitable tool for adjusting the gradients of thoracic CT imaging. NGTP can cope with any medical diagnostic display system connected with CT or MRI equipment in a network because it is in DICOM format.

Quality Control↗
PubMed2004

Adrenomedullin contributes to vascular hyporeactivity in cirrhotic rats with ascites via a release of nitric oxide.

BACKGROUND: Plasma levels of adrenomedullin, a potent vasodilator peptide, are increased in cirrhotic patients, whereas its role in vascular hyporeactivity in cirrhosis has not been clarified. METHODS: Adrenomedullin expression was evaluated by radioimmunoassay and reverse-transcription polymerase chain reaction. Vascular reactivity to phenylephrine, alpha-adrenoceptor agonist, was investigated in the aortic rings from control rats and CCl-induced cirrhotic rats with ascites in the presence of the neutralizing antibody against adrenomedullin, human adrenomedullin and/or N-nitro-L-arginine methyl ester, a nitric oxide synthase inhibitor. RESULTS: Plasma adrenomedullin levels were significantly higher in cirrhotic rats than in controls (16.3 +/- 2.9 versus 7.4 +/- 1.7 fmol/mL, P < 0.05) and correlated negatively with systemic arterial pressure (r = -0.62, P < 0.05). Gene expression of adrenomedullin in various organs (liver, kidney, lung) and vessels (portal vein, aorta) was enhanced in cirrhotic rats compared with controls. Neutralizing antibody against adrenomedullin ameliorated the blunted contractile response to phenylephrine in cirrhotic aorta (Rmax: 1.5 +/- 0.1 versus 1.0 +/- 0.1 g/mg tissue, P < 0.05), whereas contraction remained unchanged in control aorta (Rmax: 1.9 +/- 0.2 versus 1.9 +/- 0.2 g/mg tissue). Intravenous infusion of human adrenomedullin induced a reduction of mean arterial pressure together with an increase of serum nitrate levels, which was abolished by neutralizing antibody against adrenomedullin. Human adrenomedullin caused a blunted contractile response to phenylephrine in both control and cirrhotic aortas, which was not observed in the presence of N-nitro-L-arginine methyl ester. CONCLUSIONS: These findings indicate that the overproduction of adrenomedullin may contribute to vascular hyporeactivity in cirrhosis via a release of nitric oxide.

Adrenergic alpha-Agonists↗
PubMed2002

Current status of hospice cancer deaths both in-unit and at home (1995-2000), and prospects of home care services in Japan.

In Japan, the first government-approved hospice (GAH) and palliative care unit was established and commenced operations in 1990, and hospice medical care was made eligible for health insurance coverage. By 31 December 2000, the number of GAH institutions had increased to 86 (1,590 beds). The ratio of hospices to population in Japan is currently approximately 1:1.5 million, with an average of one hospice bed for approximately every 80,000 people. This study of institutions reports a survey conducted to determine the number of deaths (hospice unit and home) of GAH cancer patients, and to determine the servicing status of hospice home care for the period 1995 through 2000. The place of death of the patients cared for by GAHs in 2000 were: hospice units 97.7% and home 2.3%. GAH patient deaths (both inpatient and at home) in 2000 was 2.6% of the total number of cancer patients' deaths, an increase of 3.8-fold since 1995. Of the total number of GAH institutions, 62% are engaged in home care services and 91 % offer hospice care by hospice-assigned doctors. In addition, 72% offer team care with nurses based at Home Care Agencies. In order for the hospice (including home care service) to become established in a way most appropriate to each region of Japan, GAH institutions must assume significant promotional roles in their respective regions. One of the goals and assignments of establishing medical service with hospice home care in Japan is to develop the systematic care programs of GAH institutions, which include home care service in addition to the already established hospice unit and outpatient services.

Home Care Services↗
PubMed2001

Diastereoselective ruthenium-Cp complexation of enantiopure arene compounds possessing stereogenic benzylic alcohol functionalities.

[reaction--see text] Enantiopure (arene)ruthenium compounds possessing a stereogenic benzylic alcohol functionality were stereoselectively synthesized by diastereoselective ruthenium-Cp complexation to a distinct arene face. This diastereoselective ruthenium-Cp complexation was further extended to biaryl compounds linked with a six-membered lactone bridge for the synthesis of enantiomerically pure, axially chiral biaryls.

Journal Article↗
PubMed2001

Establishment of left-right asymmetric innervation in the lancelet oral region.

Lancelets (amphioxus) exhibit a remarkable asymmetric development in the anterior body region, which is reflected in the peripheral nervous system even at adulthood. Not all of the anterior nerves are involved, but the left third to fifth nerves are clearly asymmetric. To trace the developmental process responsible for asymmetric innervation, the peripheral nerves in the anterior region were studied in pre- and mid-metamorphic larvae, 1-cm-long juveniles, and in adults by using whole-mount immunostaining. The mouth changes in size and location during larval life before moving ventrally and, in conjunction with this change, nerves in the oral region are also modified. The left second nerve initially innervates the oral region, but this connection is secondarily lost. As the mouth expands and shifts posteriorly, the left fifth to ninth nerves join the left third and fourth in the innervation of the oral region. The left third to sixth nerves anastomose with the oral nerve ring, which encircles the mouth on the left side. In the juveniles and adults, there are two nerve plexuses that run parallel to the margin of the oral hood. The innermost of these, the "inner oral-hood nerve plexus", is asymmetrically connected with the left third to fifth nerves on both sides. The other, the "outer oral-hood nerve plexus", is ipsilaterally connected with the third to seventh nerves on both sides. The velar nerve ring is also innervated asymmetrically by the left fourth and fifth nerves. From these observations, we suggest that the oral nerve ring is the precursor of both the inner oral-hood nerve plexus and the velar nerve ring, and that the asymmetric innervation retained in adult lancelets is related to the early anastomosis of the left nerves with the oral nerve ring. We also show that, contrary to the persistent asymmetric innervation, the axonal patterns of the anterior peripheral nervous system in developing lancelets can change.

Animals↗
PubMed2001

Stereoselective synthesis of the axially chiral A-B ring system of vancomycin utilizing a planar chiral arene chromium complex.

[reaction: see text] The axial biaryl ring system of vancomycin was stereoselectively synthesized by utilizing a planar chiral tricarbonyl(arylhalide)chromium complex. Both enantiomers of the planar chiral (arylbromide)chromium complexes, (+)-9 and ent-(-)-9, can be stereoselectively transferred to an absolutely identical key intermediate 23 for the vancomycin A-B ring system by the diastereoselective Suzuki-Miyaura cross-coupling reaction as key step.

Anti-Bacterial Agents↗
PubMed2001

The formation of capsule and septum in human hepatocellular carcinoma.

The formation of fibrous capsule around the cancer nodule and of the septum in the tumor is frequently observed with the development of hepatocellular carcinoma (HCC). We aimed to clarify how the capsule and septum were formed during the growth of HCC. Liver samples surgically resected from 25 patients with HCC were studied with in situ hybridization for type-I, -III, and -IV procollagen. Type-I and -III procollagen-expressing cells, mostly alpha-smooth muscle actin (SMA)-positive, were increased in the fibrous capsule and in the septum between HCC nodules. These cells were also found at the invasion front of HCC and around the necrotic cancer tissues. Type-IV procollagen gene expression was mainly observed in mesenchymal cells localized in both HCCs and non-cancerous liver. Cancer cells or hepatocytes did not express any of these procollagen genes. The present study reveals that the capsule and septum are mainly formed by alpha-SMA-positive mesenchymal cells at the interface between two different tissues (e.g., cancer nodule vs non-cancerous liver or another cancer nodule). The wound healing occurs even in HCC. The capsule formation may result from interaction between tumor and host liver and interfere the growth and invasion of HCC.

Actins↗
PubMed2001

Endothelin-1 plays a major role in portal hypertension of biliary cirrhotic rats through endothelin receptor subtype B together with subtype A in vivo.

BACKGROUND/AIMS: Endothelin-1 has been suggested to play a key role in cirrhotic portal hypertension, but a role of its receptors in vivo is not fully elucidated. METHODS: Biliary cirrhosis was induced by bile duct ligation. Expressions of endothelin-1 and its receptors were evaluated by radioimmunoassay and/or reverse-transcription polymerase chain reaction. Hemodynamics were studied using endothelin receptor agonist or antagonist. RESULTS: Portal pressure and hepatic endothelin-1 concentrations progressively increased in parallel after bile duct ligation. Gene expression of hepatic prepro-endothelin-1 and endothelin B receptor enhanced after bile duct ligation, while that of endothelin A receptor was unchanged. Intraportal administration of endothelin-1 or endothelin B receptor agonist sarafotoxin 6c (0.5 nmol/kg, respectively) progressively raised portal pressure in both sham and cirrhotic rats. Portal hypertensive effect of sarafotoxin 6c was more intense in cirrhotic rats than sham animals. Neither endothelin A receptor antagonist FR139317 (1 mg/kg) nor endothelin B receptor antagonist BQ788 (1 mg/kg) alone ameliorated cirrhotic portal hypertension. Only the combined endothelin A and B blockade was associated with a decrease in portal pressure in cirrhotic rats. CONCLUSIONS: These results indicate that endothelin-1 plays a major role in cirrhotic portal hypertension through endothelin receptor subtype B together with subtype A in vivo.

Animals↗
PubMed2001

Control strategy for rotary blood pumps.

The control strategy for ventricular support with a centrifugal blood pump was examined in this study. The control parameter was the pump rpm that determines pump flow. Optimum control of pump rpm that reflects the body's demand is important for long-term, effective, and safe circulatory support. Moreover, continuous, reliable monitoring of ventricular function will help successfully wean the patients from the ventricular assist device (VAD). The control strategy in this study includes determination of the target pump rpm that can provide the flow required by the body, fine-rpm-tuning to minimize deleterious effects such as suction in the ventricle, and assessment of ventricular function for successful weaning from VADs. To determine the target pump rpm, we proposed to use the relation between the native heart rate and cardiac output, and the relation between the pump rpm and centrifugal pump output. For fine-tuning of the pump rpm, the motor current waveform was used. We computed the power spectral density of the motor current waveform and calculated the ratio of the fundamental to the higher order components. When this ratio was larger than approximately 0.2, we assumed there would be a suction effect in the ventricle. As for assessment of ventricular function, we used the amplitude of the motor current waveform. The control system implemented using a DSP functioned properly in the mock circulatory loop as well as in acute animal experiments. The motor current also showed a good correlation with the ventricular pressure in acute animal experiments.

Animals↗
PubMed2001

Design and evaluation of a single-pivot supported centrifugal blood pump.

In order to develop a centrifugal blood pump that meets the requirements of a long-term, implantable circulatory support device, in this study a single-pivot bearing supported centrifugal blood pump was designed to evaluate its basic performance. The single-pivot structure consisted of a ceramic ball male pivot mounted on the bottom surface of the impeller and a polyethylene female pivot incorporated in the bottom pump casing. The follower magnet mounted inside the impeller was magnetically coupled to the driver magnet mounted on the shaft of the direct current brushless motor. As the motor rotated, the impeller rotated supported entirely by a single-pivot bearing system. The static pump performance obtained in the mock circulatory loop revealed an acceptable performance as a left ventricular assist device in terms of flow and head pressure. The pump flow of 5 L/min against the head pressure of 100 mm Hg was obtained at rotational speeds of 2,000 to 2,200 rpm. The maximum pump flow was 9 L/min with 2,200 rpm. The maximum electrical-to-hydraulic power conversion efficiency was around 14% at pump flows of 4 to 5 L/min. The stability of the impeller was demonstrated at the pump rpm higher than 1,400 with a single-pivot bearing without an additional support at its top. The single-pivot supported centrifugal pump can provide adequate flow and pressure as a ventricular assist device, but its mechanical stability and hemolytic as well as thrombotic performances must be tested prior to clinical use.

Equipment Design↗
PubMed2001

Estimation of left ventricular recovery level based on the motor current waveform analysis on circulatory support with centrifugal blood pump.

In a mock circulatory loop simulating the left heart bypass using a centrifugal blood pump, analysis of the motor current waveform of the centrifugal pump was performed to derive a useful parameter to evaluate the status of ventricular function. The relationship between the peak, amplitude, and the peak of the fundamental frequency of the power spectral density of the periodic motor current waveform (MCpsdP) that reflected the pulsatile ventricular pressure, and the peak of the left ventricular pressure (LVP) was examined. Although both peak and amplitude of the motor current waveform showed an excellent correlation with the peak LVP, they failed to predict the opening of the aortic valve. The MCpsdP that corresponds to the frequency of the heart rate showed an excellent correlation with the peak LVP throughout the LVP levels, but the slope between them changed with the opening of the aortic valve. Thus, it is possible to follow the change in the LVP and detect even the opening of the aortic valve, and, hence, the recovery of the left ventricle. However, the slope of the linear regression equation varied, depending on the pump speed. This result implies that the MCpsdP can be possibly used to follow the change of ventricular function during circulatory assistance with a centrifugal blood pump as well as to control the pump speed in response to varying ventricular function.

Centrifugation↗