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Biomedical subjects

H Watanabe

Publications and source records attributed to H Watanabe.

At least 19 recordsLinked to original sources

The relation between spike-timing dependent plasticity and Ca2+ dynamics in the hippocampal CA1 network.

In our previous study, spike timing dependent synaptic plasticity (STDP) was investigated in the CA1 area of rat hippocampal slices using optical imaging. It was revealed that the profiles of STDP could be classified into two types depending upon layer specific location along the dendrite. The first was characterized by a symmetric time window observed in the proximal region of the stratum radiatum (SR), and the second by an asymmetric time window in the distal region of the SR. Our methods involved the bath-application of bicuculline (GABA(A) receptor antagonist) to hippocampal slices, which revealed that GABAergic interneuron projections were responsible for the symmetry of a time window. In this study, the intracellular Ca2+ increase of hippocampal CA1 neurons, induced by the protocol of timing between pre- and post-synaptic excitation (i.e. STDP protocol), was measured spatially by using optical imaging to investigate how the triggering of STDP is dependent on intracellular calcium concentration. We found that the magnitude of STDP was closely related to the rate of Ca2+ increase ("velocity") of calcium transient during application of induction stimuli. Location dependency was also analyzed in terms of Ca2+ influx. Furthermore, it was shown that decay time constant of Ca2+ dynamics during the application of STDP-inducing stimuli was also significantly correlated with STDP.

Action Potentials↗

The Wnt code: cnidarians signal the way.

Cnidarians are the simplest metazoans with a nervous system. They are well known for their regeneration capacity, which is based on the restoration of a signalling centre (organizer). Recent work has identified the canonical Wnt pathway in the freshwater polyp Hydra, where it acts in organizer formation and regeneration. Wnt signalling is also essential for cnidarian embryogenesis. In the sea anemone Nematostella vectensis 11 of the 12 known wnt gene subfamilies were identified. Different wnt genes exhibit serial and overlapping expression domains along the oral-aboral axis of the embryo (the 'wnt code'). This is reminiscent of the hox code (cluster) in bilaterian embryogenesis that is, however, absent in cnidarians. It is proposed that the common ancestor of cnidarians and bilaterians invented a set of wnt genes that patterned the ancient main body axis. Major antagonists of Wnt ligands (e.g. Dkk 1/2/4) that were previously known only from chordates, are also present in cnidarians and exhibit a similar conserved function. The unexpectedly high level of genetic complexity of wnt genes evolved in early multi-cellular animals about 650 Myr ago and suggests a radical expansion of the genetic repertoire, concurrent with the evolution of multi-cellularity and the diversification of eumetazoan body plans.

Animals↗

A retrospective analysis of the use of brachytherapy in relation to early stage squamous cell carcinoma of the oropharynx and its relationship to second primary respiratory and upper digestive tract cancers.

The purpose of this study was to retrospectively evaluate brachytherapy for early stage squamous cell carcinoma of the oropharynx (SCO) in relation to second primary respiratory and upper digestive tract cancers (RUDT). Between 1976 and 2001, 111 previously untreated patients with stage I or II SCO were treated with Au-198 seed brachytherapy alone (36 cases) or Au-198 seed brachytherapy plus external irradiation (75 cases). Of the 111 patients, 28 patients had stage I disease and 83 patients had stage II disease. Each patient was evaluated for therapeutic efficacy, post-treatment quality of life (QOL) and a second cancer. The 5-year and 10-year cause-specific actuarial survival rates for stage I and II SCO were 87% and 86%, respectively. We found that the 5-year and 10-year survival rates for all SCOs combined with second primary RUDT cancers were 71% and 45%, respectively. 51 second primary RUDT cancers occurred successively in 41 patients following treatment for early stage oropharyngeal cancer and this was the sole prognostic factor by the multivariate analysis. Au-198 seed brachytherapy with or without ipsilateral external irradiation of up to 30 Gy was associated with fewer late complications in the oral cavity and salivary gland. We concluded that our treatment policy of brachytherapy with or without external irradiation for patients with early stage SCO was effective and acceptable from the standpoint of tumour control and post-treatment QOL.

Adult↗

Short report: antimicrobial susceptibility and genetic characteristics of Haemophilus influenzae isolated from patients with respiratory tract infections between 1987 and 2000, including beta-lactamase-negative ampicillin-resistant strains.

The minimum inhibitory concentration (MIC) of five antibiotics and the presence of resistance genes was determined in 163 Haemophilus influenzae isolates collected over 13 years (1987-2000) in four two-yearly sampling periods from patients with respiratory tract infections. The prevalence of beta-lactamase-negative ampicillin-susceptible strains was approximately 80% over the sampling period although fewer strains (65.9%) were recovered in the period 1995-1997. TEM-1 type beta-lactamase-producing strains were less frequent starting at 15.6% and declining to 2.2% in the final sampling period. Low-beta-lactamase-negative ampicillin-resistant (BLNAR) strains were uncommon in 1987-1989 (2.2%), peaked to 19.5% in 1995-1997, but fell back to 11.1% by 2000. Fully BLNAR strains were not detected until the last sampling period (6.7%). The MICs of ampicillin, levofloxacin, cefditoren and ceftriaxone remained stable but there was an eight-fold increase in the MIC of cefdinir over the sampling period. Pulsed-field gel electrophoresis of DNA digests showed that three representative BLNAR strains were genetically distinct and 11 DNA profiles were identified among 17 low-BLNAR strains. These data suggest that the number of genetically altered BLNAR and low-BLNAR strains are increasing in Japan.

Ampicillin↗

Alkene/diamond liquid/solid interface characterization using internal photoemission spectroscopy.

The photochemical attachment of 10-amino-dec-1-ene molecules protected with a trifluoroacetic acid group (TFAAD) on hydrogen-terminated single-crystalline chemical vapor deposited (CVD) diamond is characterized by total photoyield spectroscopy (TPYS), conductivity, Hall-effect, spectrally resolved photoconductivity (SPC), optical transmission experiments, and, for the first time, by in situ internal photoemission (IPE) spectroscopy applied in the spectral regime from 4 to 6 eV on the alkene/diamond (liquid/solid) heterostructures. These experiments are performed on undoped, (100) oriented, single-crystalline CVD diamond films, which contain no grain boundaries and have negligible bulk and surface defect densities. X-ray photoelectron spectroscopy (XPS) is used to investigate the chemical bonding of alkene molecules to diamond. The spectroscopic set of data shows that the photochemical reaction window of H-terminated diamond is shifted below the optical gap of diamond because of the negative electron affinity. In situ IPE experiments reveal electron emission between 4.5 and 5.2 eV. A model is introduced and discussed in which valence-band electrons are optically excited into empty hydrogen-induced surface states of diamond from where they tunnel into empty pi states of alkene molecules. We theoretically discuss the fastest attachment time to achieve a saturated TFAAD layer of about 2 x 10(14) cm(-)(2) on diamond, which is experimentally detected to be 7 h. In the case of direct optical electron excitations from diamond, the bonding efficiency will be one TFAAD molecule attachment arising from about 1600 emitted electrons.

Alkenes↗

Phase shift of subthreshold theta oscillation in hippocampal CA1 pyramidal cell membrane by excitatory synaptic inputs.

Hippocampal CA1 neurons receive multiple rhythmical inputs with relatively independent phases during theta activity. It, however, remains to be determined how these multiple rhythmical inputs affect oscillation properties in membrane potential of the CA1 pyramidal cell. In order to investigate oscillation properties in the subthreshold membrane potential, we generated oscillations in the membrane potential of the CA1 pyramidal cells in rat hippocampal slices in vitro with a sinusoidal current injection into the pyramidal soma at theta band frequencies (4-7 Hz), and analyzed effect of rhythmically excitatory synaptic inputs. The Schaffer collaterals were stimulated with a cyclic Gaussian stimulation method, whose pulse intervals were distributed at 10 pulses/cycle (5 cycles/s). We found that the cyclic Gaussian stimulations induced membrane potential oscillations and their phase delays from the mean of the pulse distribution were dependent on membrane potential oscillation amplitude. We applied four pairs of cyclic Gaussian stimulations and somatic sinusoidal current stimulations at the same frequency (5 Hz) with varying phase differences (-pi/2, 0, pi/2, pi rad). The paired stimulations induced phase distributions of the oscillation in the membrane potential, which showed a dependency on an increasing membrane potential oscillation amplitude response to cyclic Gaussian stimulation. This membrane potential dynamic was exhibited by the mixture of the membrane potential oscillation-amplitude-dependent phase delay and the linear summation of the two sinusoidal waves. These suggest that phases of the membrane potential oscillation are modulated by excitatory synaptic inputs. This phase-modulation by excitatory synaptic inputs may play a crucial role for memory operation in the hippocampus.

Animals↗

Antimicrobial susceptibility and serotype distribution of Streptococcus pneumoniae isolated from patients with community-acquired pneumonia and molecular analysis of multidrug-resistant serotype 19F and 23F strains in Japan.

A nationwide study was undertaken to determine the susceptibility to penicillin and serotypes of Streptococcus pneumoniae in Japan. S. pneumoniae was isolated from 114 adult patients with community-acquired pneumonia over 22 months at 20 hospitals and medical centres in different regions in Japan. All but five isolates were from sputum. Forty-eight isolates (42.1%) were susceptible, 40 (35.1%) showed intermediate resistance (MIC, 0.12-1.0 microg/ml) and 26 (22.8%) were resistant (MIC, >or=2.0 microg/ml) to penicillin G. All isolates were susceptible to ceftriaxone (breakpoint 1 microg/ml), imipenem (4 microg/ml) and vancomycin (4 microg/ml). Most were resistant to erythromycin, clarithromycin and azithromycin; only two were resistant to levofloxacin. Differences were found in the distribution of serotypes among isolates showing susceptibility to penicillin (predominant types 3, 6B, and 19F), intermediate resistance (6B, 14, 19F, and 23F) and full resistance (19F and 23F). PFGE typing showed that 14 of the 25 strains of serotype 19F had a single DNA profile, pattern A, a pattern closely similar to that of the Taiwan multidrug-resistant 19F clone. Twelve pattern A strains were not susceptible to penicillin but carried the macrolide resistance gene mef(A). The DNA profiles of the 15 strains of 23F were also heterogeneous but six were highly similar (pattern b) yet distinct from the Spanish multidrug-resistant 23F clone although possibly related to the Taiwan multidrug-resistant 23F clone. The pattern b strains were not susceptible to penicillin and also harboured either mef(A) or erm(B). Our results indicate that multidrug-resistant pneumococci are spreading rapidly in Japan. Efforts to prevent the spread of the pandemic multidrug-resistant serotypes should be intensified.

Anti-Bacterial Agents↗

Search for the invisible decay of neutrons with KamLAND.

The Kamioka Liquid scintillator Anti-Neutrino Detector is used in a search for single neutron or two-neutron intranuclear disappearance that would produce holes in the -shell energy level of (12)C nuclei. Such holes could be created as a result of nucleon decay into invisible modes (inv), e.g., n--> 3v or nn--> 2v. The deexcitation of the corresponding daughter nucleus results in a sequence of space and time-correlated events observable in the liquid scintillator detector. We report on new limits for one- and two-neutron disappearance: tau(n--> inv) > 5.8 x 10(29) years and tau (nn--> inv) > 1.4 x 10(30) years at 90% C.L. These results represent an improvement of factors of approximately 3 and >10(4) and over previous experiments.

Journal Article↗

Sports exercise effect on shortening of saccadic reaction time associated with neck extensor muscle activity.

We investigated sports exercise effect on shortening of saccadic reaction time associated with neck extensor muscle activity. Saccadic reaction time was measured in neck rest position, 20 degrees neck flexion, and 30 % muscle contraction of the shoulder girdle elevators for two groups. These groups were an untrained group that has never belonged to any sports club (UT group) and a group that has belonged to high-speed ball sports clubs (HS group). In the neck flexion and 30 % muscle contraction conditions, there was a significant shortening of the reaction time for the HS group. For the UT group, no significant shortening was found in those conditions, and the reaction time in the 30 % contraction was rather significantly longer than that in the rest position. Sports experience pursuing a high-speed ball will be effective in the shortening of the saccadic reaction time associated with the activity of neck extensors.

Adult↗

SWI/SNF complex is essential for NRSF-mediated suppression of neuronal genes in human nonsmall cell lung carcinoma cell lines.

Mammalian chromatin remodeling factor, SWI/SNF complex contains a single molecule of either Brm or BRG1 as the ATPase catalytic subunit. Here, we show that the SWI/SNF complex forms a larger complex with neuron-restrictive silencer factor (NRSF) and its corepressors, mSin3A and CoREST, in human nonsmall cell lung carcinoma cell lines. We also demonstrate that the strong transcriptional suppression of such neuron-specific genes as synaptophysin and SCG10 by NRSF in these non-neural cells requires the functional SWI/SNF complex; these neuronal genes were elevated in cell lines deficient in both Brm and BRG1, whereas retrovirus vectors expressing siRNAs targeting integral components of SWI/SNF complex (Brm/BRG1 or Ini1) induced expression of these neuronal genes in SWI/SNF-competent cell lines. In cell lines deficient in both Brm and BRG1, exogenous Brm or BRG1 suppressed expression of these neuronal genes in an ATP-dependent manner and induced efficient and specific deacetylation of histone H4 around the NRSF binding site present in the synaptophysin gene by a large complex containing the recruited functional SWI/SNF complex. Patients with Brm/BRG1-deficient lung carcinoma have been reported to carry poor prognosis; derepression of NRSF-regulated genes including these neuron-specific genes could contribute to enhance tumorigenicity and also would provide selective markers for Brm/BRG1-deficient tumors.

Base Sequence↗

Differential expression and pathological significance of autocrine motility factor/glucose-6-phosphate isomerase expression in human lung carcinomas.

To clarify the involvement of autocrine motility factor (AMF) in the phenotype and biological profiles of human lung carcinomas, we analysed protein and mRNA expression in a total of 180 cases. Immunohistochemistry revealed positive staining in 67.2%, with the highest frequency in squamous cell carcinoma (SCC; 90.8%) and the lowest in small cell carcinoma (SmCC; 27.8%). In SCC, the staining frequency and intensity correlated with the degree of morphological differentiation. Generally, the expression levels in immunoblotting analysis corresponded well with immunohistochemical positivity. However, there was less agreement between protein and mRNA levels: in SmCC and large cell carcinomas (LCCs), mRNA showed higher, but protein showed lower expression. Among non-small cell lung carcinomas (NSCLCs), AMF protein levels correlated inversely with tumour size, but tumours exhibiting lymph node metastasis showed higher mRNA expression. In cultured lung carcinoma cells which comprised all histological subtypes, AMF was detected in the lysates of all ten cell lines. Secreted AMF protein was detected in the conditioned media from six cell lines, most of which were SmCC or LCC. Thus, a particular subset of lung carcinomas secrete AMF, which may promote cell motility via autocrine stimulation through its cognate receptor and cause the biological aggressiveness seen in SmCC and LCC. Moreover, treatment by proteasome inhibitors resulted in increased cellular AMF in five cell lines, suggesting that intracellular AMF levels are regulated by both secretion and proteasome-dependent degradation. In conclusion, AMF was detected in a major proportion of lung carcinomas, and may play a part not only in proliferation and/or progression of the tumours, but also, possibly, in the differentiation of SCC. Furthermore, higher mRNA expression may be related to the high metastatic potential of NSCLC and increased protein secretion, leading to a more aggressive phenotype, such as the invasiveness of SmCC and LCC.

Adenocarcinoma↗

Calcium signalling in the endothelium.

Elevations in cytosolic Ca2+ concentration are the usual initial response of endothelial cells to hormonal and chemical transmitters and to changes in physical parameters, and many endothelial functions are dependent upon changes in Ca2+ signals produced. Endothelial cell Ca2+ signalling shares similar features with other electrically non-excitable cell types, but has features unique to endothelial cells. This chapter discusses the major components of endothelial cell Ca2+ signalling.

Animals↗

Outbreak of Legionnaires' disease on a cruise ship linked to spa-bath filter stones contaminated with Legionella pneumophila serogroup 5.

In January 2003, two cases of Legionnaires' disease associated with a ship's cruise were registered in the database of National Epidemiological Surveillance of Infectious Diseases. A 70-year-old male heavy smoker with mild emphysema contracted the disease during a cruise. Legionella pneumophila serogroup (sg) 5 was isolated from the patient's sputum and the ship's indoor spa. The isolate from the spa matched the patient's isolate by genotyping performed by pulsed-field gel electrophoresis (PFGE). The second case was in a 73-year-old female. During epidemiological investigation, a third case of Legionnaire's disease in a 71-year-old male was subsequently diagnosed among passengers on the same ship on the following cruise. Environmental investigation revealed that porous natural stones (Maifanshi) in the filters of the spas had harboured L. pneumophila, a phenomenon which has not been reported except in Japan. This is the first documented evidence of L. pneumophila sg 5 infection on a ship and of porous stones as a source of Legionella infection.

Aged↗

Peripheral blood stem cell mobilization by granulocyte colony-stimulating factor alone and engraftment kinetics following autologous transplantation in children and adolescents with solid tumor.

In 56 pediatric and adolescent patients (median age 7 years, range 1-21) with various solid tumors, peripheral blood stem cells (PBSC) were mobilized with granulocyte colony-stimulating factor (G-CSF) alone, and the yields of PBSC and engraftment kinetics following autologous peripheral blood stem cell transplantation (PBSCT) were evaluated retrospectively. Granulocyte colony-stimulating factor (10 microg/kg) was injected subcutaneously for mobilization when patients showed no influence of previous chemotherapy, and administration was continued for 5 days. The peaks of CD34+ cells and colony-forming units-granulocyte/macrophage in the blood were observed on days 4 through 6 of G-CSF administration in all patients. Peripheral blood stem cell harvest was commenced on day 5 of G-CSF treatment. Compared to the results in patients mobilized by chemotherapy plus G-CSF (N=18), the progenitor cell yields were lower in patients mobilized with G-CSF alone. However, there were no significant differences in WBC and ANC engraftment compared to the chemotherapy plus G-CSF mobilization group. Platelet recovery following autologous PBSCT was delayed in patients mobilized with G-CSF alone. The median time taken for ANC and platelet counts to reach 0.5 x 10(9) and 20 x 10(9)/l was 12 days (range: 9-28) and 15 days (8-55), respectively, in all patients who received PBSC mobilized by G-CSF alone. In summary, mobilization with G-CSF alone can mobilize sufficient CD34+ cells for successful autografting and sustained hematological reconstitution in pediatric and adolescent patients with solid tumors, and even in heavily pre-treated patients.

Adolescent↗

Transplantation of autologous rabbit BM-derived mesenchymal stromal cells embedded in hyaluronic acid gel sponge into osteochondral defects of the knee.

BACKGROUND: Mesenchymal stromal cells (MSC) have the potential to differentiate into distinct mesenchymal tissues including cartilage, suggesting that these cells are an attractive cell source for cartilage tissue engineering approaches. Various methods, such as using hyaluronan-based materials, have been employed to improve transplantation for repair. Our objective was to study the effects of autologous transplantation of rabbit MSC with hyaluronic acid gel sponges into full-thickness osteochondral defects of the knee. METHODS: Rabbit BM-derived MSC were cultured and expanded with fibroblast growth factor (FGF). Specimens were harvested at 4 and 12 weeks after implantation, examined histologically for morphologic features, and stained immunohistochemically for type II collagen and CD44. RESULTS: The regenerated area after autologous transplantation of hyaluronic acid gel sponge loaded with MSC into the osteochondral defect at 12 weeks after surgery showed well-repaired cartilage tissue, resembling the articular cartilage of the surrounding structure, of which the histologic score was significantly better than that of the untreated osteochondral defect. In the regenerated cartilage, type II collagen was found in the pericellular matrix of regenerative chondrocytes, while CD44 expression in the regenerative tissue could not be revealed. DISCUSSION: These data suggest that the autologous transplantation of MSC embedded in hyaluronan-based material may support chondrogenic differentiation and be useful for osteochondral defect repair.

Animals↗