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Biomedical subjects

Hirokazu Tanaka

Publications and source records attributed to Hirokazu Tanaka.

At least 19 recordsLinked to original sources

Stepwise guest adsorption with large hysteresis in a coordination polymer {[Cu(bhnq)(THF)2](THF)}n constructed from a flexible hingelike ligand.

Reversible vapochromic behavior of a porous copper(II) coordination polymer {[Cu(bhnq)(THF)2](THF)}n (1; THF = tetrahydrofuran) constructed from a flexible hingelike ligand H2bhnq [2,2'-bis(3-hydroxy-1,4-naphthoquinone)] has been investigated by adsorption measurements. The isotherms show large hysteretic and stepwise profiles, suggesting the occurrence of the guest-induced framework transformation. The dynamic coil-like behavior of 1 can be controlled through the change of the hydrogen-bonding interactions caused by the reversible and selective incorporation of guest molecules.

Journal Article↗

Distribution of neuropeptide W immunoreactivity and mRNA in adult rat brain.

Neuropeptide W (NPW) is a recently identified neuropeptide that binds to G-protein-coupled receptor (GPR) 7, which is highly expressed in several discrete regions of the rodent brain including the central amygdaloid nucleus and bed nucleus of the stria terminalis. Although several reports suggested that NPW is implicated in the regulation of energy homeostasis and nociception, the precise physiological role of NPW has remained unclear. In this study, we examined distribution of NPW messenger RNA and NPW immunoreactivity in the adult rat brain. NPW-immunoreactive (ir) cells were detected in the ventral tegmental area, periaqueductal gray, and Edinger-Westphal nucleus. NPW-ir fibers were observed in several brain regions, including the lateral septum, bed nucleus of the stria terminalis, dorsomedial and posterior hypothalamus, central amygdaloid nucleus, CA1 field of hippocampus, interpeduncular nucleus, inferior colliculus, lateral parabrachial nucleus, facial nucleus, and hypoglossal nucleus. NPW-ir fibers were most abundantly observed in the central amygdaloid nucleus and the bed nucleus of the stria terminalis, which are regions implicated in fear and anxiety. These results suggest that NPW might be involved in the regulation of stress and emotive responses, especially in fear and anxiety-related physiological and behavioral functions.

Animals↗

Online analysis method for intrinsic signal optical imaging.

The intrinsic optical imaging technique has been widely applied for the visualization of functional maps in the sensory cortices of mammals. Many current studies refer this mapping in order to focus thereafter on particular features, at some particular locations: a fast and accurate mapping is therefore required. However, even during a successful experiment, the recorded raw data are usually contaminated by some kinds of noise that cannot necessarily be averaged out over the trials. An adequate image data analysis method has to be applied to extract signals closely related neural activities in response to presented stimuli. Thus far two different analysis methods could be adopted: the band-pass filtering and the GIF method [Yokoo T, Knight BW, Sirovich L. An optimization approach to signal extraction from noisy multivariate data. NeuroImage 2001:14;1309-26]. While the latter one is very efficient but requires the whole data in order to maximize the signal to noise ratio, the simple band-pass filtering technically reaches its limits very quickly. Here we propose another filtering method based on the polynomial subtraction of spatially smoothly modulated components. This simple method can visualize well-organized iso-orientation domains of the cat visual cortex with reliability similar to more sophisticated ones while allowing an online visualization of the clean data.

Action Potentials↗

An optimization principle for determining movement duration.

Movement duration is an integral component of motor control, but nearly all extant optimization models of motor planning prefix duration instead of explaining it. Here we propose a new optimization principle that predicts movement duration. The model assumes that the brain attempts to minimize movement duration under the constraint of meeting an accuracy criterion. The criterion is task and context dependent but is fixed for a given task and context. The model determines a unique duration as a trade-off between speed (time optimality) and accuracy (acceptable endpoint scatter). We analyzed the model for a linear motor plant, and obtained a closed-form equation for determining movement duration. By solving the equation numerically with specific plant parameters for the eye and arm, we found that the model can reproduce saccade duration as a function of amplitude (the main sequence), and arm-movement duration as a function of the ratio of target distance to size (Fitts's law). In addition, it explains the dependency of peak saccadic speed on amplitude and the dependency of saccadic duration on initial eye position. Furthermore, for arm movements, the model predicts a scaling relationship between peak velocity and distance and a reduction in movement duration with a moderate increase in viscosity. Finally, for a linear plant, our model predicts a neural control signal identical to that of the minimum-variance model set to the same movement duration. This control signal is a smooth function of time (except at the endpoint), in contrast to the discontinuous bang-bang control found in the time-optimal control literature. We suggest that one aspect of movement planning, as revealed by movement duration, may be to assign an endpoint accuracy criterion for a given task and context.

Algorithms↗

Chemical reaction at specific sites and reaction-induced self-assembly as observed by in situ and real time SANS: enzymatic polymerization to synthetic cellulose.

We have investigated the self-assembling process of cellulose artificially synthesized via enzymatic polymerization by means of in situ and time-resolved SANS (small-angle neutron scattering). The results elucidated the following: (i) Cellulose molecules synthesized at a special reaction site of the enzyme (cellulase) located on or near the smooth surface of self-assembled enzymes formed in the reaction medium. (ii) The synthesized molecules associated themselves via DLA (diffusion-limited association) and crystallized into fibrils. (iii) The fibrils formed the aggregates, which had surface fractal dimension D(s) increasing from 2 to 2.3 with the reaction time, on the smooth surface of the enzyme aggregates.

Biocompatible Materials↗

Chronic intracerebroventricular administration of relaxin-3 increases body weight in rats.

Bolus-administered intracerebroventricular (ICV) relaxin-3 has been reported to increase feeding. In this study, to examine the role of relaxin-3 signaling in energy homeostasis, we studied the effects of chronically administered ICV relaxin-3 on body weight gain and locomotor activity in rats. Two groups of animals received vehicle or relaxin-3 at 600 pmol/head/day, delivered with Alzet osmotic minipumps. In animals receiving relaxin-3, food consumption and weight gain were statistically significantly higher than those in the vehicle group during the 14-day infusion. During the light phase on days 2 and 7 and the dark phase on days 3 and 8, there was no difference in locomotor activity between the two groups. Plasma concentrations of leptin and insulin in rats chronically injected with relaxin-3 were significantly higher than in the vehicle-injected controls. These results indicate that relaxin-3 up-regulates food intake, leading to an increase of body weight and that relaxin-3 antagonists might be candidate antiobesity agents.

Animals↗

Real-time 3-D echocardiographic evaluation of the fetal heart using instantaneous volume-rendered display.

AIM: Using new real-time 3-D fetal echocardiography with instantaneous volume-rendered display, we evaluated the heart anatomy of a number of normal fetuses during pregnancy. METHODS: Eighteen normal fetuses in 17 pregnancies (16 singletons and one twin) at 18-38 weeks' gestation were studied using a transabdominal real-time 3-D ultrasound machine. This machine proved capable of providing continuous 3-D sonographic images every 0.05 and 0.035 s without the need for an external workstation or other additional, costly equipment. For each patient, the fetal heart was first monitored using conventional 2-D echocardiography and was monitored again within 10 min using real-time 3-D echocardiography. RESULTS: Consecutive real-time 3-D images showing a four-chamber view, long-axis view, short-axis view, and right ventricular outflow tract view were obtained in 100%, 66.6%, 38.8%, and 22.2% of fetuses in the study, respectively. Morphological changes to each atrium or ventricle could be observed clearly and in detail throughout the cardiac cycle. The opening and closing of each valve were clearly visible. Moreover, these observations could be made from any direction. CONCLUSIONS: Real-time 3-D echocardiography provides a novel means for evaluation of the fetal heart in 3-D in real time in the second and third trimester of pregnancy. Real-time 3-D echocardiography may be an important modality in future fetal cardiac research and in evaluation of congenital heart disease in the fetus.

Echocardiography, Three-Dimensional↗

HOX decoy peptide enhances the ex vivo expansion of human umbilical cord blood CD34+ hematopoietic stem cells/hematopoietic progenitor cells.

HOX transcription factors play important roles in the self-renewal of hematopoietic cells. HOX proteins interact with the non-HOX homeobox protein PBX1 to regulate, both positively and negatively, the expression of target genes. In this study, we synthesized a decoy peptide containing the YPWM motif from HOX proteins (decoy HOX [decHOX]), which was predicted to act as a HOX mimetic, and analyzed its effects on self-renewal of human cord blood CD34(+) cells. We were able to deliver decHOX into approximately 70% of CD34(+) cells. By examining the expression of HOX target genes c-myc and p21(waf1/cip1), we confirmed that decHOX enhanced HOX functions. After 7 days of culture in serum-free medium containing a cytokine cocktail, cultures treated with decHOX had approximately twofold-increased numbers of CD34(+) cells and primitive multipotent progenitor cells compared with control cells. Furthermore, decHOX-treated cells reconstituted hematopoiesis in nonobese diabetic/severe combined immunodeficiency mice more rapidly and more effectively (more than twofold greater efficiency, as determined by a limiting dilution method) than control cells. decHOX-treated cells were also able to repopulate secondary recipients. Together, these results indicate that in combination with growth factors and/or other approaches, decHOX might be a useful new tool for the ex vivo expansion of hematopoietic stem/progenitor cells.

Animals↗

Real-time 3-D sonographic observation of fetal facial expression.

AIM: There have been a few reports about 3-D sonographic observation of fetal movements using dynamic 3-D sonography. However, dynamic 3-D sonography is not real-time, the frame rate being in the region of 4-6 frames per second depending on the size of the region of interest and the number of lines employed. Recently, a new faster 3-D sonography, which acquires up to 28 frames per second, has become available. Using this system, we studied a full range of fetal facial expressions during pregnancy. METHODS: A total of 17 normal fetuses in 16 pregnancies (15 singletons and one twin) at 20-38 weeks' gestation was studied using a transabdominal real-time 3-D ultrasound machine. This 3-D ultrasound machine proved capable of providing continuous 3-D sonographic images every 0.05 and 0.035 s. The fetal face was monitored for 15 min for each subject. RESULTS: Fetal eyelid movement (fetal blinking) was observed in three of 17 fetuses (17.6%). Double blinking was identified in one fetus at 38 weeks. Various types of mouth movement (yawning, a little opening, chewing, and subtle lip movement) could be observed in nine of 17 fetuses (52.9%). In the course of yawn-like opening of the mouth, tongue movements such as tongue thrust and tongue click were clearly shown in three fetuses (17.6%). A lingula movement was also identified in the course of tongue movement. CONCLUSION: Real-time 3-D sonography provides a novel means for evaluation of fetal movement, particularly fetal facial expression, in the second and third trimesters. Real-time 3-D sonography might be an important modality in future fetal behavior research and in evaluation of fetal well-being.

Face↗

Comparison of post-exercise and post-vasodilator stress myocardial stunning as assessed by electrocardiogram-gated single-photon emission computed tomography.

BACKGROUND: Exercise gated single-photon emission computed tomography (SPECT) using technetium-99m (99mTc)-sestamibi evaluates both myocardial perfusion during stress and wall motion >30 min after the stress, which has the potential to assess not only exercise-induced myocardial ischemia but also the development of myocardial stunning. METHODS AND RESULTS: To evaluate the incidence of post-stress myocardial stunning, as well as comparing the effects of different stress methods on the development of stunning, 179 consecutive patients with known or suspected coronary artery disease (CAD) underwent (99m)Tc-sestamibi SPECT with either exercise (n=135) or adenosine triphosphate disodium (ATP) (n=44). Electrocardiogram-gated SPECT images were acquired >30 min after the stress and again 4 h later, and perfusion and wall motion were evaluated. Post-stress myocardial stunning occurred in 24 patients (13%): 22 after exercise and 2 after ATP stress. The magnitude of the transient wall motion abnormality after exercise was greater in patients with severe ischemia, compared with those with mild-to-moderate ischemia (p<0.0001). By contrast, with ATP stress, the magnitude of the transient wall motion abnormality was similar, regardless of the severity of perfusion abnormality. Furthermore, a significant correlation between summed difference score and transient wall motion abnormality was found after exercise (r=0.68, p<0.0001). With ATP, however, no such correlation was observed (r=0.28, p=NS). CONCLUSIONS: Using 99mTc-sestamibi gated SPECT, myocardial stunning is frequently observed after exercise and correlates with the severity of myocardial ischemia, but this does not occur with ATP, which is regarded as a specific marker for severe CAD.

Adenosine Triphosphate↗

Diagnostic value of simultaneous brachial and ankle blood pressure measurements for the extent and severity of coronary artery disease as assessed by myocardial perfusion imaging.

BACKGROUND: Although the simultaneous measurement of brachial and ankle blood pressure is a simple method of evaluating atherosclerosis, its diagnostic value for coronary artery disease (CAD) is undetermined. METHODS AND RESULTS: To evaluate the diagnostic value of ankle-brachial pressure index (ABI) and brachial-to-ankle pulse wave velocity (baPWV), 334 consecutive patients with suspected CAD were evaluated. Patients with a previous myocardial infarction or coronary intervention were not included. The magnitude of myocardial ischemia was evaluated by myocardial perfusion imaging. Using a 20-segment model, the percent of ischemic segments to total segments was expressed as %myocardium ischemic. In patients with < or =1, 2 and > or =3 coronary risk factors, %myocardium ischemic was 2.7+/-0.4, 4.0+/-0.5, 7.9+/-0.8%, respectively (p<0.0001 for trend). Performing ABI with a cutoff of 1, the %myocardium ischemic was similar in patients with < or =1 or 2 risk factors. In patients with > or =3 coronary risk factors, however, an ABI <1 reflected greater %myocardium ischemic than an ABI > or =1 (10.1+/-1.3, 6.6+/-1.0%; p=0.03). No such additional value was observed with baPWV. CONCLUSIONS: The addition of simultaneous brachial and ankle blood pressure measurements will help further stratify patients with multiple risk factors. Although this approach is simple, it facilitates the identification of high-risk patients who require aggressive treatment because >10% myocardium ischemic is regarded as a scintigraphic indicator for coronary revascularization.

Aged↗

Value of pharmacologic stress myocardial perfusion imaging for preoperative risk stratification for aortic surgery.

BACKGROUND: Aortic surgery is an invasive, high-risk noncardiac procedure and the patients who require it have a high prevalence of coronary artery disease. Therefore, preoperative risk stratification for this subset is essential. METHODS AND RESULTS: To assess the perioperative risk for aortic surgery, pharmacologic stress single-photon emission computed tomography (SPECT) was performed in 302 patients: aortic dissection in 56, thoracic aortic aneurysm in 124, and abdominal aortic aneurysm in 122. Not only was the presence or absence of perfusion defects analyzed, but also the 20-segment model. Pharmacologic thallium SPECT revealed negative findings in 210 patients and positives in 92. Perioperative cardiac events occurred in 9 patients: 7 occurred in patients with positive SPECT, and in only 2 of those with negative SPECT (2/210 vs 7/92; p<0.05). Multivariate analysis using logistic regression model revealed that a summed stress score>or=14 was the most important factor to identify patients who subsequently had perioperative cardiac events. CONCLUSIONS: Pharmacologic stress SPECT has significant value in the risk stratification of patients before aortic surgery. In patients with positive SPECT, an aggressive approach to reduce the preoperative risk is necessary, whereas aortic surgery can be performed safely in patients with negative SPECT.

Aged↗

[Characteristics of prostatic cancer in men with a serum prostate-specific antigen level of < or =4.0 ng/ml].

Fifteen out of 140 men (median age 67 years, range 62-75) had a serum prostate-specific antigen (PSA) level of < or = 4 ng/ml before radical prostatectomy which was performed without preoperative neoadjuvant hormonal therapy between 2001 January and 2004 September. Demographic and clinical data were analyzed. Pathological specimens were evaluated by routine hematoxylin and eosine staining and immunohistochemistry with anti-PSA antibody, for both pathological staging and grading, and for the presence of PSA production. Pathological data were compared between patients with PSA < or = 4 ng/ml and those with 4 < PSA < or = 10 ng/ml. Clinically insignificant cancer was defined as a cancer volume of < 0.5 ml and the Gleason score < or = 6. The median PSA level was 3.0 ng/ml (range 1.4-3.9). Thirteen tumors (87%) were pT2. One tumor had a Gleason score of 7 and 14 tumors had a final Gleason score of < or = 6. Nine (60%) tumors were clinically insignificant. Comparison of pathological variables, PSA < or = 4 ng/ml cancer had a significantly lower Gleason score (p = 0.0029), and a smaller cancer volume (p = 0.0451) than 4 < PSA < or = 10 ng/ml cancer. All tumors were stained strongly for PSA. During a median follow-up of 24 (9-36) months, no patient showed elevated PSA (PSA > or = 0.1 ng/ml). Most prostate cancers in men with a PSA level of < or = 4 ng/ml were pT2, and about half of them were clinically insignificant. All cancers produced PSA.

Aged↗

Preoperative risk stratification for endovascular surgery using pharmacologic stress myocardial imaging.

To stratify perioperative cardiac risk for endovascular surgery, pharmacologic stress single-photon emission computed tomography (SPECT) was performed in 206 patients. Of 8 patients who had cardiac events, 7 occurred in 67 patients with positive SPECT results, whereas only 1 occurred in 139 patients with negative SPECT results (7 of 67 vs 1 of 139, p <0.002). Furthermore, a scintigraphic marker of a summed stress score >/=14 was the most important factor identifying patients who subsequently had cardiac events by multivariate analysis.

Aged↗

Notch signals inhibit the development of erythroid/megakaryocytic cells by suppressing GATA-1 activity through the induction of HES1.

The effects of Notch signals on the erythroid/megakaryocytic differentiation of hematopoietic cells were examined. Activation of Notch signals by the intracellular Notch1 or an estradiol-inducible form of Notch1/ER suppressed the expression of the erythroid marker glycophorin A in an erythroid/megakaryocytic cell line K562. Although Mock-transfected K562 cells underwent megakaryocytic differentiation in response to 12-O-tetradecanoylphorbol-13-acetate (TPA), estradiol-activated Notch1/ER induced apoptosis during TPA treatment in the transfectant, which was accompanied by the reduced expression of an antiapoptotic molecule Bcl-XL. Even when apoptosis was prevented by the overexpression of Bcl-XL, activated Notch signals still inhibited TPA-induced megakaryocytic differentiation. As for this mechanism, Notch1/recombination signal binding protein J-kappa-induced HES1 but not HES5 was found to inhibit the function of an erythroid/megakaryocytic lineage-specific transcription factor GATA-1. Although HES1 did not affect the DNA binding activity of GATA-1 in gel shift and chromatin immunoprecipitation assays, it directly bound to GATA-1 and dissociated a critical transcriptional cofactor, p300, from GATA-1. Furthermore, overexpressed HES1 inhibited the development of erythroid and megakaryocytic cells in colony assays. Also, the Notch ligand Jagged1 expressed on NIH3T3 cells suppressed the development of erythroid and megakaryocytic cells from cocultured Lin-Sca-1+ hematopoietic stem/progenitor cells. These results suggest that Notch1 inhibits the development of erythroid/megakaryocytic cells by suppressing GATA-1 activity through HES1.

Animals↗

NF-kappaB family proteins participate in multiple steps of hematopoiesis through elimination of reactive oxygen species.

To examine the roles for NF-kappaB family proteins in hematopoiesis, we first expressed dominant negative Rel/NF-kappaB(IkappaBSR) in a factor-dependent cell line, Ba/F3. Although IkappaBSR neither affected thrombopoietin-dependent nor gp130-mediated growth, it suppressed interleukin-3- and erythropoietin-dependent growth at low concentrations. In addition, IkappaBSR enhanced factor-deprived apoptosis through the accumulation of reactive oxygen species (ROS). When expressed in normal hematopoietic stem/progenitor cells, IkappaBSR induced apoptosis even in the presence of appropriate cytokines by accumulating ROS. We also expressed IkappaBSR in an inducible fashion at various stages of hematopoiesis using the OP9 system, in which hematopoietic cells are induced to develop from embryonic stem cells. When IkappaBSR was expressed at the stage of Flk-1(+) cells (putative hemangioblasts), IkappaBSR inhibited the development of primitive hematopoietic progenitor cells by inducing apoptosis through the ROS accumulation. Furthermore, when IkappaBSR was expressed after the development of hematopoietic progenitor cells, it inhibited their terminal differentiation toward erythrocytes, megakaryocytes, and granulocytes by inducing apoptosis through the ROS accumulation. These results indicate that NF-kappaB is required for preventing apoptosis at multiple steps of hematopoiesis by eliminating ROS.

Animals↗

Prepro-orexin mRNA expression in the rat brain is increased during pregnancy.

The purpose of this study was to investigate whether orexin expression in the rat brain was changed during pregnancy. Brain samples were obtained from 5 nonpregnant rats and 10 pregnant rats (5; day 10 of gestation, and 5; day 20 of gestation). Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis was performed to investigate the expression of prepro-orexin mRNA and the housekeeping gene in the rat brain. The signals were quantified by the densitometric analysis. The distribution and expression of orexin-A and orexin-B were determined using immunohistochemistry. The ratio of the prepro-orexin mRNA expressions to the housekeeping gene expression in pregnant rat brain were significantly higher than that in nonpregnant control. There was no significant difference between prepro-orexin mRNA levels of day 10 and day 20 of gestation. Immunohistochemical staining for orexin-A and orexin-B was present in neurons within and around the lateral and posterior hypothalamic areas in both nonpregnant and pregnant rats. These results suggest that increased prepro-orexin mRNA levels at early gestational age in the maternal rat has a role on energy metabolism during pregnancy.

Actins↗

Variants of the orexin2/hcrt2 receptor gene identified in patients with excessive daytime sleepiness and patients with Tourette's syndrome comorbidity.

The orexin-2/hypocretin-2 (OX2R) receptor gene is mutated in canine narcolepsy and disruption of the prepro-orexin/hypocretin ligand gene results in both an animal model of narcolepsy and sporadic cases of the human disease. This evidence suggests that the structure of the OX2R gene, and its homologue, the OX1R gene, both members of the G protein-coupled receptor (GPCR) family, and the gene encoding the peptide ligands, the prepro-orexin/hypocretin gene, may be variables in the etiology of sleep disorders. We report a single stranded conformational polymorphism (SSCP) analysis of the coding regions of these genes in idiopathic sleep disorder patients diagnosed with excessive daytime sleepiness (EDS) (n = 28), narcolepsy (n = 28), Tourette's syndrome/chronic vocal or motor tic disorder (n = 70), and control subjects (n = 110). Two EDS patients showed a Pro11Thr change. One Tourette's syndrome patient was found to have a Pro10Ser alteration. The Pro10Ser and Pro11Thr variants were not found in non-disease populations. Analysis of the ability of the mutant receptors to mobilize calcium compared to the wild-type receptor in response to orexin agonists indicated that they resulted in decreased potency at high (etaM) concentrations of orexin ligands. Further work is warranted to study the variability of the orexin/hypocretin system in a variety of disorders characterized by EDS.

Amino Acid Sequence↗