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Biomedical subjects

M Tamura

Publications and source records attributed to M Tamura.

At least 235 records · Page 13Linked to original sources
PubMed1999

Results of screening for cancer in Japanese in the prime of life--an analysis of nationwide MHTS and human dry dock statistics--Preventive Medicine Committee of the Japan Hospital Association.

The nationwide survey of institutions with MHTS and human dry dock capabilities was analyzed and the following results have been obtained. 1) The relative rates of cancer detection by sex and organ were the stomach > colon > rectum > lung > kidney > esophagus for men and the stomach > breast > uterus > colon > thyroid > lung for women. 2) Gastric cancer takes first place in the ranking of rates of cancer detection in the population of both sexes, followed by colon cancer. The difference in rate of detection between these cancers has been narrowed from year to year. In 1997, the ratio of gastric to colon cancers was 10:7. 3) Early cancers account for 74% of gastric cancer patients and 75% of colon cancer patients. 4) Since gastric and colon cancers are detected early, the proportions of persons with gastrointestinal symptoms are as low as 28% for gastric cancer patients and 26% for colon cancer patients. 5) The relative rates of cancer detection by the degree obesity are normal > obese > lean person. The rates of gastric and colon cancers are 2- and 3-fold higher for obese persons than for lean persons, respectively. Gastric and colon cancers are detected with higher frequency in well-nourished persons. The present review of the national MHTS and human dry dock statistics has confirmed the efficacy of MHTS and human dry dock, especially in the examination for gastrointestinal cancers.

Adult↗
PubMed1998

Tumor suppressor PTEN inhibits integrin- and growth factor-mediated mitogen-activated protein (MAP) kinase signaling pathways.

The tumor suppressor PTEN dephosphorylates focal adhesion kinase (FAK) and inhibits integrin-mediated cell spreading and cell migration. We demonstrate here that expression of PTEN selectively inhibits activation of the extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase (MAPK) pathway. PTEN expression in glioblastoma cells lacking the protein resulted in inhibition of integrin-mediated MAP kinase activation. Epidermal growth factor (EGF) and platelet-derived growth factor (PDGF)- induced MAPK activation were also blocked. To determine the specific point of inhibition in the Ras/Raf/ MEK/ERK pathway, we examined these components after stimulation by fibronectin or growth factors. Shc phosphorylation and Ras activity were inhibited by expression of PTEN, whereas EGF receptor autophosphorylation was unaffected. The ability of cells to spread at normal rates was partially rescued by coexpression of constitutively activated MEK1, a downstream component of the pathway. In addition, focal contact formation was enhanced as indicated by paxillin staining. The phosphatase domain of PTEN was essential for all of these functions, because PTEN with an inactive phosphatase domain did not suppress MAP kinase or Ras activity. In contrast to its effects on ERK, PTEN expression did not affect c-Jun NH2-terminal kinase (JNK) or PDGF-stimulated Akt. Our data suggest that a general function of PTEN is to down-regulate FAK and Shc phosphorylation, Ras activity, downstream MAP kinase activation, and associated focal contact formation and cell spreading.

Adaptor Proteins, Signal Transducing↗
PubMed1998

Isolated and companion young brown dwarfs in the taurus and chamaeleon molecular clouds

Infrared imaging observations have detected a dozen faint young stellar objects (YSOs) in the Taurus and Chamaeleon molecular clouds whose near-infrared colors are similar to those of classical T Tauri stars (TTS). They are around four magnitudes fainter than low-luminosity YSOs in Taurus detected in earlier surveys and as much as eight magnitudes fainter than typical TTS. The extreme faintness of the objects and their lower luminosity relative to previously identified brown dwarfs in the Pleiades indicate that these faint YSOs are very young brown dwarfs on the order of 1 million years old.

Journal Article↗
PubMed1998

Flavin-containing monooxygenase mediated metabolism of benzydamine in perfused brain and liver.

Benzydamine (BZY) N-oxidation mediated by flavin-containing monooxygenase (FMO) was evaluated in perfused brain and liver. Following 20 min of perfusion with modified Ringer solution, the infusion of BZY into brain or liver led to production of BZY N-oxide. BZY N-oxide, a metabolite of BZY oxidized exclusively by FMO, was mostly recovered in the effluent without undergoing further metabolism or reduction back to the parent substrate. The BZY N-oxide formation rate increased as the infusion concentration of BZY increased both in perfused brain and perfused liver. BZY N-oxidation activities in perfused rat brain and liver were 4.2 nmol/g brain/min and 50 nmol/g liver/min, respectively, although the BZY N-oxidation activity in brain homogenates was one 4000th that in liver homogenates. This is the first study of FMO activity in brain in situ.

Animals↗
PubMed1998

In situ morphometric analysis of the coronary arterial growth in perinatal rats.

The perinatal changes in the diameters of left and right coronary arteries in rats were studied using the rapid whole body freezing technique. The main portion of the left coronary artery and left anterior descending and circumflex branches rapidly increased in diameter after birth as well as ascending aorta. The ratios of the diameters of the left coronary artery and anterior descending branch to the diameter of ascending aorta increased significantly after 4 days of age. In contrast, there were no significant changes in the diameter of the right coronary artery from the fetus to the 8-day-old pups and the ratio of the right coronary artery to the ascending aorta significantly decreased after birth. We report here that the left coronary artery in rats increases in diameter more rapidly than the right coronary artery in the early newborn period.

Animals↗
PubMed1998

Optical characterization of heme a + a3 and copper of cytochrome oxidase in blood-free perfused rat brain.

For the precise examination of the optical characteristics of cerebral tissue, we prepared hemoglobin-free perfused rat heads, from which trace amounts of blood were completely removed. In this preparation at 30 degrees C, the redox responses of the cytochrome oxidase components, heme a + a3 and copper, were followed spectrophotometrically in visible and near-infrared regions, and were correlated with the changes in neural activity as monitored by electroencephalography (EEG). During the aerobic-anaerobic transition, there was clear dissociation of the time courses of the reduction of heme a + a3 and copper; the reduction of heme a + a3 preceded the reduction of copper. The EEG activity decreased earlier than the reduction of heme a + a3. Pentylenetetrazole administration in normoxia caused the partial reduction of heme a + a3 but not of copper. The redox behaviors of cytochrome oxidase components in the brain were identical to those observed in isolated mitochondria. The usefulness of brain preparation for bridging the in vivo and in vitro studies is documented where various circulatory parameters could be controlled artificially.

Aerobiosis↗
PubMed1998

Circular polarization in star- formation regions: implications for biomolecular homochirality

Strong infrared circular polarization resulting from dust scattering in reflection nebulae in the Orion OMC-1 star-formation region has been observed. Circular polarization at shorter wavelengths might have been important in inducing chiral asymmetry in interstellar organic molecules that could be subsequently delivered to the early Earth by comets, interplanetary dust particles, or meteors. This could account for the excess of L-amino acids found in the Murchison meteorite and could explain the origin of the homochirality of biological molecules.

Journal Article↗
PubMed1998

Circular polarization in star-formation regions: implications for biomolecular homochirality.

Strong infrared circular polarization resulting from dust scattering in reflection nebulae in the Orion OMC-1 star-formation region has been observed. Circular polarization at shorter wavelengths might have been important in inducing chiral asymmetry in interstellar organic molecules that could be subsequently delivered to the early Earth by comets, interplanetary dust particles, or meteors. This could account for the excess of L-amino acids found in the Murchison meteorite and could explain the origin of the homochirality of biological molecules.

Amino Acids↗
PubMed1998

Measurement of postprandial remnant-like particles (RLPs) following a fat-loading test.

To assess the usefulness of remnant-like particles (RLPs), which represent potentially atherogenic lipoprotein remnants, as an index of postprandial hyperlipidemia, RLPs and other lipids were measured in 19 healthy adults (23-44 years old) after ingestion of a test meal (fat content, 32.9%). The lipoprotein derivatives, with a marked increase after fat-loading, were triglycerides, retinyl palmitate and RLPs. The retinyl palmitate peak lagged behind the RLP and triglyceride peaks, indicating that it may have different kinetics than RLP and triglyceride. While triglycerides are considered as an index of atherosclerotic risk factor, RLPs also may be a suitable index for evaluating postprandial hyperlipidemia. RLPs remained high even 8 h after fat-loading, suggesting that the postprandial state persists for almost the whole day. Accordingly, it may be important to assess postprandial remnant concentrations.

Adult↗
PubMed1998

Inhibition of cell migration, spreading, and focal adhesions by tumor suppressor PTEN.

The tumor suppressor PTEN is a phosphatase with sequence similarity to the cytoskeletal protein tensin. Here the cellular roles of PTEN were investigated. Overexpression of PTEN inhibited cell migration, whereas antisense PTEN enhanced migration. Integrin-mediated cell spreading and the formation of focal adhesions were down-regulated by wild-type PTEN but not by PTEN with an inactive phosphatase domain. PTEN interacted with the focal adhesion kinase FAK and reduced its tyrosine phosphorylation. Overexpression of FAK partially antagonized the effects of PTEN. Thus, PTEN phosphatase may function as a tumor suppressor by negatively regulating cell interactions with the extracellular matrix.

3T3 Cells↗
PubMed1998

RNA heptamers that direct RNA cleavage by mammalian tRNA 3' processing endoribonuclease.

Mammalian tRNA 3' processing endoribonuclease (3' tRNase) can recognize and cleave any target RNA that forms a precursor tRNA-like complex with another RNA. Various sets of RNA molecules were tested to identify the smallest RNA that can direct target RNA cleavage by 3' tRNase. A 3' half tRNAArgwas cleaved efficiently by 3' tRNase in the presence of small 5' half tRNAArgvariants, the D stem-loop region of which was partially deleted. Remarkably, 3' tRNase also cleaved the 3' half tRNAArgin the presence of a 7 nt 5' tRNAArg composed only of the acceptor stem region with a catalytic efficiency comparable with that of cleavage directed by an intact 5' half tRNAArg. The catalytic efficiency of cleavage directed by the heptamer decreased as the stability of the T stem-loop structures of 3' half tRNAArg variants decreased. No heptamer-directed cleavage of a 3' half tRNAArg without T stem base pairs was detected. A heptamer also directed cleavage of an HIV-1 RNA containing a stable hairpin structure. These findings suggest that in the presence of an RNA heptamer, 3' tRNase can discriminate and eliminate target RNAs that possess a stable hairpin adjacent to the heptamer binding sequence from a large complex RNA pool.

Animals↗
PubMed1998

Abrogation of bronchial eosinophilic inflammation and airway hyperreactivity in signal transducers and activators of transcription (STAT)6-deficient mice.

Signal transducers and activators of transcription 6 (STAT6) is essential for interleukin 4-mediated responses, including class switching to IgE and induction of type 2 T helper cells. To investigate the role of STAT6 in allergic asthma in vivo, we developed a murine model of allergen-induced airway inflammation. Repeated exposure of actively immunized C57BL/6 mice to ovalbumin (OVA) aerosol increased the level of serum IgE, the number of eosinophils in bronchoalveolar lavage (BAL) fluid, and airway reactivity. Histological analysis revealed peribronchial inflammation with pulmonary eosinophilia in OVA-treated mice. In STAT6-deficient (STAT6-/-) C57BL/6 mice treated in the same fashion, there were no eosinophilia in BAL and significantly less peribronchial inflammation than in wild-type mice. Moreover STAT6-/- mice had much less airway reactivity than wild-type mice. These findings suggest that STAT6 plays a crucial role in the pathogenesis of allergen-induced airway inflammation.

Animals↗
PubMed1998

Synthesis and structure-activity relationships of carboxyflavones as structurally rigid CysLT1 (LTD4) receptor antagonists.

The synthesis and CysLT1 receptor affinities of a new series of highly rigid 3'- and 4'-(2-quinolinylmethoxy)- or 3'- and 4'-[2-(2-quinolinyl)ethenyl]-substituted, 6-, 7-, or 8-carboxylated flavones are described. CysLT1 receptor affinities of the flavones (down to 11 nM) were determined by their ability to displace [3H]LTD4 from its receptor in guinea pig lung membranes. Structure-affinity relationship studies showed that the relative positions of the carboxylic acid and the quinoline moiety were critical for CysLT1 affinities. While the carboxyl is optimal in the 8 position but tolerated in the 6 position, only the 6- and not the 8-tetrazole has significant activity. The quinoline moiety may be connected to the flavone skeleton by an ethenyl or a methoxy linker, but the substitution position is important for high affinity, especially in the 6-carboxylated flavones. 4'-Substituted 6-carboxyflavones are essentially inactive, whereas the 3'-substituted analogues have submicromolar CysLT1 affinity. Replacement of the quinoline by other heteroaromates generally leads to decreased affinities, with the phenyl and naphthyl analogues displaying only little or no affinity, while the 7-chloroquinoline analogue is comparable in activity to the quinoline. Flavones having CysLT1 receptor affinities of 10-30 nM were selected for determination of their inhibitory effects on the LTD4-induced contraction of guinea pig ileum in vitro. The IC50 values ranged between 15 and 100 nM. Compound 5d (8-carboxy-6-chloro-3'-(2-quinolinylmethoxy)flavone, VUF 5087) was selected for further research because of its high potency in the functional assay. This series contains the most rigid CysLT1 receptor antagonists known to date, and they are useful in the development of a CysLT1 antagonist model, which is discussed in the companion paper.

Animals↗
PubMed1998

Relationship between fluctuations in the cerebral hemoglobin oxygenation state and neuronal activity under resting conditions in man.

Simultaneous measurements by near-infrared spectroscopy and electroencephalography were performed during 15-min resting periods in nine healthy adult brains. The peak frequencies of the frontal and occipital rhythms varied with the time course like the hemoglobin oxygenation state. Changes in the amount of oxygenated hemoglobin in the frontal region by more than 50% of the maximum resting variation range were accompanied by changes in peak frequency at the electrode position between two optodes. The results suggest that spontaneous neuronal activity is responsible for fluctuations in the hemoglobin oxygenation state in the resting state.

Adult↗
PubMed1998

Effect of the long-term feeding of dietary lipids on the learning ability, fatty acid composition of brain stem phospholipids and synaptic membrane fluidity in adult mice: a comparison of sardine oil diet with palm oil diet.

The effect of 12 month feeding of 5% palm oil or sardine oil diet on the maze-learning ability, fatty acid composition of brain stem phospholipids and synaptic membrane fluidity in mice was studied. The time required to reach the maze exit and the number of times that a mouse strayed into blind alleys in the maze were measured three times every 4 days. The time and number of mice fed on the sardine oil diet were less than those of animals fed on the palm oil diet in the first and second trials. The results of fatty acid composition analysis of brain stem phosphatidylethanolamine showed that the percentage of docosahexaenoic acid (22:6, n-3; DHA) was higher, but the arachidonic acid (20:4, n-6; AA) and docosatetraenoic acid (22:4, n-6; DTA) were lower in the sardine oil diet fed-mice than in the palm oil diet fed-animals. Moreover, the microviscosity of the synaptic plasma membrane in the sardine oil diet group was lower than that in the palm oil diet group. These results suggest that the adult mice fed on the sardine oil diet for a long period maintain higher levels of docosahe xaenoic acid in brain phospholipids, synaptic membrane fluidity and maze-learning ability than animals fed on the palm oil diet.

Animals↗
PubMed1998

In vitro neuronal and glial production and differentiation of human central neurocytoma cells.

Human central neurocytoma cells were cultured and characterized immunophenotypically and electrophysiologically to clarify their developmental potential. We conducted systematic in vitro studies utilizing fresh tissues from three patients. Initially small homogeneous cell clusters settled down onto the bottom of the culture flasks, and, after 2 weeks from plating, mature neuron-like cells developed from these clusters and expressed neurofilament proteins (NF: specific neuronal markers). On the other hand, approximately 80% of small round cell clusters and flat glial-like cells from which these clusters developed were positively stained for glial fibrillary acidic protein (GFAP: a specific glial marker). Furthermore these neuronal and glial cells showed distinct morphology, and dual-label, indirect immunohistochemistry for GFAP and NF-200 kD disclosed that the two antigens were not found co-localized in the same cells. In single-cell clonal analysis, neuronal, glial, and mixed neuronal and glial clones were generated. Electrophysiologically, the cells of neuronal morphology possessed sodium channels, and also L-type calcium channels in whole-cell voltage clamp. The sodium channels were of a characteristic neuronal phenotype which appears in neurons. These findings suggest that small round human central neurocytoma cells exhibit both neuronal and glial differentiations and have the properties reminiscent of precursor cells derived from subventricular matrix; thus, these cultured cells may be a potential source for investigations of human CNS neuronal and glial development and differentiation.

Adult↗
PubMed1998

Changes in superior vena cava velocity patterns in normal neonates.

We demonstrated serial changes in the flow velocity patterns of both the superior vena cava and the tricuspid flow velocity patterns during the first day of life. These changes in waveforms may be related to alterations in loading conditions induced by the closing process of the ductus arteriosus.

Blood Flow Velocity↗