Hiroshi Takahashi - Academia.edu (original) (raw)
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Papers by Hiroshi Takahashi
Molecular therapy : the journal of the American Society of Gene Therapy, Jan 4, 2017
The retina is an ideal target for gene therapy because of its easy accessibility and limited immu... more The retina is an ideal target for gene therapy because of its easy accessibility and limited immunological response. We previously reported that intravitreally injected adeno-associated virus (AAV) vector transduced the inner retina with high efficiency in a rodent model. In large animals, however, the efficiency of retinal transduction was low, because the vitreous and internal limiting membrane (ILM) acted as barriers to transduction. To overcome these barriers in cynomolgus monkeys, we performed vitrectomy (VIT) and ILM peeling before AAV vector injection. Following intravitreal injection of 50 μL triple-mutated self-complementary AAV serotype 2 vector encoding EGFP, transduction efficiency was analyzed. Little expression of GFP was detected in the control and VIT groups, but in the VIT+ILM group, strong GFP expression was detected within the peeled ILM area. To detect potential adverse effects, we monitored the retinas using color fundus photography, optical coherence tomography...
Molecular vision, 2016
We examined the neuroprotective effects of exogenous brain-derived neurotrophic factor (BDNF), wh... more We examined the neuroprotective effects of exogenous brain-derived neurotrophic factor (BDNF), which provides protection to retinal ganglion cells (RGCs) in rodents, in a model of transient intraocular pressure (IOP) elevation using a mutant (triple Y-F) self-complementary adeno-associated virus type 2 vector encoding BDNF (tm-scAAV2-BDNF). The tm-scAAV2-BDNF or control vector encoding green fluorescent protein (GFP; tm-scAAV2-GFP) was intravitreally administered to rats, which were then divided into four groups: control, ischemia/reperfusion (I/R) injury only, I/R injury with tm-scAAV2-GFP, and tm-scAAV2-BDNF. I/R injury was then induced by transiently increasing IOP, after which the rats were euthanized to measure the inner retinal thickness and cell counts in the RGC layer. Intravitreous injection of tm-scAAV2-BDNF resulted in high levels of BDNF expression in the neural retina. Histological analysis showed that the inner retinal thickness and cell numbers in the RGC layer were p...
The transient X-ray binary pulsar A0535+262 was observed with Suzaku on 2005 September 14 when th... more The transient X-ray binary pulsar A0535+262 was observed with Suzaku on 2005 September 14 when the source was in the declining phase of the August-September minor outburst. The ~103 s X-ray pulse profile was strongly energy dependent, a double peaked profile at soft X-ray energy band (<3 keV) and a single peaked smooth profile at hard X-rays. The width of the primary dip is found to be increasing with energy. The broad-band energy spectrum of the pulsar is well described with a Negative and Positive power-law with EXponential (NPEX) continuum model along with a blackbody component for soft excess. A weak iron K_alpha emission line with an equivalent width ~25 eV was detected in the source spectrum. The blackbody component is found to be pulsating over the pulse phase implying the accretion column and/or the inner edge of the accretion disk may be the possible emission site of the soft excess in A0535+262. The higher value of the column density is believed to be the cause of the secondary dip at the soft X-ray energy band. The iron line equivalent width is found to be constant (within errors) over the pulse phase. However, a sinusoidal type of flux variation of iron emission line, in phase with the hard X-ray flux suggests that the inner accretion disk is the possible emission region of the iron fluorescence line.
Http Dx Doi Org 10 1080 00222349908248112, Dec 14, 2006
ABSTRACT Isotactic polypropylene consisting of uniaxially oriented β-phase lamellae was crystalli... more ABSTRACT Isotactic polypropylene consisting of uniaxially oriented β-phase lamellae was crystallized in a temperature gradient. The β → α transition was investigated by simultaneous measurements with differential scanning calorimetry (DSC) and X-ray diffraction using synchrotron radiation (SR). To compare the transition mechanism, the β-phase sample was deformed by rolling it along the direction of the crystallization. During rolling, the β-crystal is deformed by interlamellar and interchain slip, which induces c-axis-oriented molecules along the rolling direction. The melting behavior is changed by the rolling deformation. For the as-grown β-crystal, the DSC thermogram has three peaks: the β-melting endotherm at 150°C, an exotherm by recrystallization into the α-form, and the endotherm at 167°C caused by melting of the recrystallized α-form. After the rolling deformation, the β-endotherm is extinguished by the successive exotherm. Simultaneous X-ray measurements reveal that the β → α transition is shifted to a lower temperature and that the recrystallized α-form has a c-axis-orientation caused by the rolling deformation. In the process of the β → α transition, higher-order lamellar structure is developed earlier than formation of the crystalline structure. In this study, the heating phenomena, such as the β → α transition and thickening of the β- and α-lamellae, are consistently explained by a mechanism involving melting and subsequent recrystallization.
![Research paper thumbnail of [BIS monitoring is useful for reliable intraoperative cortical mapping during brain tumor operations]](https://attachments.academia-assets.com/53380296/thumbnails/1.jpg)
](No Shinkei Geka Neurological Surgery, Dec 1, 2002
Lightwave Technology Journal of, Jun 1, 2006
In this paper, ultradense wavelength-division multiplexing (WDM) transmission technologies are di... more In this paper, ultradense wavelength-division multiplexing (WDM) transmission technologies are discussed, and a field demonstration of over-1000-channel ultradense WDM transmission is reported. The generation of an ultradense WDM signal using a supercontinuum multicarrier source that generates more than 1000 carriers and uniform precise channel spacing of 6.25 GHz is presented. The influence of four-wave-mixing generated in the transmission fiber and the requirements placed on the WDM multiplexer and demultiplexer is described. An over-1000-channel ultradense WDM transmission experiment is reported. A 1046 × 2.67-Gbit/s 6.25-GHz-spaced ultradense WDM signal is successfully transmitted over 126 km of field-installed fibers in the test bed of JGN II.
Ieice Transactions on Electronics, Oct 1, 2001
Acta Crystallographica Section F Structural Biology and Crystallization Communications, Jul 1, 2007
Tau-tubulin kinase 2 (TTBK2) is a Ser/Thr kinase that putatively phosphorylates residues Ser208 a... more Tau-tubulin kinase 2 (TTBK2) is a Ser/Thr kinase that putatively phosphorylates residues Ser208 and Ser210 (numbered according to a 441-residue human tau isoform) in tau protein. Functional analyses revealed that a recombinant kinase domain (residues 1–331) of human TTBK2 expressed in insect cells with a baculovirus overexpression system retains kinase activity for tau protein. The kinase domain of TTBK2 was crystallized using the hanging-drop vapour-diffusion method. The crystals belong to space group P212121, with unit-cell parameters a = 55.6, b = 113.7, c = 117.3 Å, α = β = γ = 90.0°. Diffraction data were collected to 2.9 Å resolution using synchrotron radiation at BL24XU of SPring-8.
Chemical Physics Letters, 1998
It is demonstrated that the Van der Waals loop appearing in the computer simulations almost vanis... more It is demonstrated that the Van der Waals loop appearing in the computer simulations almost vanishes by modifying the shape of the simulation cell even when small size systems are treated. After a long molecular dynamics simulation, it was found that the complete phase separation into vapor and liquid took place in the unstable region. The surface free energy of the interface between the liquid and vapor phases is suggested to be a major reason why the artificial loop has been observed in molecular dynamics simulations. We show that the loop depth diminishes as the box ratio of the simulation cell is enlarged.
Idiopathic interstitial fibrosis (IPF) is a chronic, usually fatal lung disease of unknown etiolo... more Idiopathic interstitial fibrosis (IPF) is a chronic, usually fatal lung disease of unknown etiology. There are few specific therapies for acute exacerbation of IPF and factors predicting the onset or severity of this syndrome are not clearly understood. A neutrophil elastase inhibitor, sivelestat (ONO-5046) has been commercially available in Japan since 2002. This inhibitor has a potent effect in the treatment of ALI/ARDS. To evaluate the outcome of patients with acute exacerbation of IPF treated with sivelestat and estimate prognostic factors, we investigated 10 patients with acute exacerbation of IPF who were intubated and mechanically ventilated. We analyzed the outcome of patients with acute exacerbation of IPF until day 180 and measured the P/F ratio, PEEP levels, the values of peripheral white blood cell number, and C-reactive protein (CRP) on day 0, 3, 7 after admission. Serum KL-6 and surfactant protein D (SP-D) concentration on day 0 were also analyzed. All patients were treated with sivelestat and methylprednisolone (mPSL) pulse therapy for 3 days from day 0 and maintenance therapy with prednisone (0.5 mg/kg/day) were continued. Of the 10 patients. 4 patients had survived (40%) and 6 patients had died (60%) at day 180 from the onset of acute exacerbation of IPF. In survivors, P/F ratio, PEEP levels, and CRP values significantly improved on day 7 (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.05). Serum KL-6 and SP-D were lower in survivors on day 0 (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.05). Taken together, serum KL-6 and SP-D may prove valuable as biochemical markers of prognosis in acute exacerbation of IPF. Sivelestat may have potential in the treatment of acute exacerbation of IPF.
Gan to Kagaku Ryoho Cancer Chemotherapy, May 1, 2006
The objective of this study was to evaluate the efficacy and toxicity of carboplatin plus weekly ... more The objective of this study was to evaluate the efficacy and toxicity of carboplatin plus weekly paclitaxel as first-line therapy in patients with advanced non-small cell lung cancer (NSCLC). Forty-nine patients were analyzed retrospectively. Every 4 weeks patients received 70 mg/m(2)paclitaxel on days 1, 8, and 15, and AUC 5-6 carboplatin on day 1. A median of four cycles (range, 1-7) was administered. Twenty-four patients had a partial response, and the overall response rate was 48.9%. The median survival time was 12.8 months and the 1-year survival was 50.7%. Overall toxicities were mild. The most common toxicity was neutropenia, grade 3/4 in 32% of the patients. Grade 3/4 hematologic toxicities included anemia (16%) and thrombocytopenia (8%). Grade 3/4 non-hematologic toxicities included febrile neutropenia (2%), pneumonia (10%) and interstitial pneumonia (2%). Grade 2 peripheral neuropathy was seen in one patient (2%). These results demonstrate that this regimen is an active and tolerable treatment for patients with advanced NSCLC. It is suggested that this weekly regimen should be considered as one of the standard therapies for future chemotherapy in advanced NSCLC.
Electrochimica Acta, 2008
The stabilization of superprotonic phase in neat CsH2PO4 and CsH2PO4/SiO2 composites as well as t... more The stabilization of superprotonic phase in neat CsH2PO4 and CsH2PO4/SiO2 composites as well as the anomalous phase transformation with a large hysteresis was investigated through proton conductivity, thermal analysis and Raman spectroscopy. The reversibility of the transition to the superprotonic phase and the phase transformation between monoclinic phase and cubic phase in neat CsH2PO4 at around Tc=230°C was confirmed under
Molecular therapy : the journal of the American Society of Gene Therapy, Jan 4, 2017
The retina is an ideal target for gene therapy because of its easy accessibility and limited immu... more The retina is an ideal target for gene therapy because of its easy accessibility and limited immunological response. We previously reported that intravitreally injected adeno-associated virus (AAV) vector transduced the inner retina with high efficiency in a rodent model. In large animals, however, the efficiency of retinal transduction was low, because the vitreous and internal limiting membrane (ILM) acted as barriers to transduction. To overcome these barriers in cynomolgus monkeys, we performed vitrectomy (VIT) and ILM peeling before AAV vector injection. Following intravitreal injection of 50 μL triple-mutated self-complementary AAV serotype 2 vector encoding EGFP, transduction efficiency was analyzed. Little expression of GFP was detected in the control and VIT groups, but in the VIT+ILM group, strong GFP expression was detected within the peeled ILM area. To detect potential adverse effects, we monitored the retinas using color fundus photography, optical coherence tomography...
Molecular vision, 2016
We examined the neuroprotective effects of exogenous brain-derived neurotrophic factor (BDNF), wh... more We examined the neuroprotective effects of exogenous brain-derived neurotrophic factor (BDNF), which provides protection to retinal ganglion cells (RGCs) in rodents, in a model of transient intraocular pressure (IOP) elevation using a mutant (triple Y-F) self-complementary adeno-associated virus type 2 vector encoding BDNF (tm-scAAV2-BDNF). The tm-scAAV2-BDNF or control vector encoding green fluorescent protein (GFP; tm-scAAV2-GFP) was intravitreally administered to rats, which were then divided into four groups: control, ischemia/reperfusion (I/R) injury only, I/R injury with tm-scAAV2-GFP, and tm-scAAV2-BDNF. I/R injury was then induced by transiently increasing IOP, after which the rats were euthanized to measure the inner retinal thickness and cell counts in the RGC layer. Intravitreous injection of tm-scAAV2-BDNF resulted in high levels of BDNF expression in the neural retina. Histological analysis showed that the inner retinal thickness and cell numbers in the RGC layer were p...
The transient X-ray binary pulsar A0535+262 was observed with Suzaku on 2005 September 14 when th... more The transient X-ray binary pulsar A0535+262 was observed with Suzaku on 2005 September 14 when the source was in the declining phase of the August-September minor outburst. The ~103 s X-ray pulse profile was strongly energy dependent, a double peaked profile at soft X-ray energy band (<3 keV) and a single peaked smooth profile at hard X-rays. The width of the primary dip is found to be increasing with energy. The broad-band energy spectrum of the pulsar is well described with a Negative and Positive power-law with EXponential (NPEX) continuum model along with a blackbody component for soft excess. A weak iron K_alpha emission line with an equivalent width ~25 eV was detected in the source spectrum. The blackbody component is found to be pulsating over the pulse phase implying the accretion column and/or the inner edge of the accretion disk may be the possible emission site of the soft excess in A0535+262. The higher value of the column density is believed to be the cause of the secondary dip at the soft X-ray energy band. The iron line equivalent width is found to be constant (within errors) over the pulse phase. However, a sinusoidal type of flux variation of iron emission line, in phase with the hard X-ray flux suggests that the inner accretion disk is the possible emission region of the iron fluorescence line.
Http Dx Doi Org 10 1080 00222349908248112, Dec 14, 2006
ABSTRACT Isotactic polypropylene consisting of uniaxially oriented β-phase lamellae was crystalli... more ABSTRACT Isotactic polypropylene consisting of uniaxially oriented β-phase lamellae was crystallized in a temperature gradient. The β → α transition was investigated by simultaneous measurements with differential scanning calorimetry (DSC) and X-ray diffraction using synchrotron radiation (SR). To compare the transition mechanism, the β-phase sample was deformed by rolling it along the direction of the crystallization. During rolling, the β-crystal is deformed by interlamellar and interchain slip, which induces c-axis-oriented molecules along the rolling direction. The melting behavior is changed by the rolling deformation. For the as-grown β-crystal, the DSC thermogram has three peaks: the β-melting endotherm at 150°C, an exotherm by recrystallization into the α-form, and the endotherm at 167°C caused by melting of the recrystallized α-form. After the rolling deformation, the β-endotherm is extinguished by the successive exotherm. Simultaneous X-ray measurements reveal that the β → α transition is shifted to a lower temperature and that the recrystallized α-form has a c-axis-orientation caused by the rolling deformation. In the process of the β → α transition, higher-order lamellar structure is developed earlier than formation of the crystalline structure. In this study, the heating phenomena, such as the β → α transition and thickening of the β- and α-lamellae, are consistently explained by a mechanism involving melting and subsequent recrystallization.
No Shinkei Geka Neurological Surgery, Dec 1, 2002
Lightwave Technology Journal of, Jun 1, 2006
In this paper, ultradense wavelength-division multiplexing (WDM) transmission technologies are di... more In this paper, ultradense wavelength-division multiplexing (WDM) transmission technologies are discussed, and a field demonstration of over-1000-channel ultradense WDM transmission is reported. The generation of an ultradense WDM signal using a supercontinuum multicarrier source that generates more than 1000 carriers and uniform precise channel spacing of 6.25 GHz is presented. The influence of four-wave-mixing generated in the transmission fiber and the requirements placed on the WDM multiplexer and demultiplexer is described. An over-1000-channel ultradense WDM transmission experiment is reported. A 1046 × 2.67-Gbit/s 6.25-GHz-spaced ultradense WDM signal is successfully transmitted over 126 km of field-installed fibers in the test bed of JGN II.
Ieice Transactions on Electronics, Oct 1, 2001
Acta Crystallographica Section F Structural Biology and Crystallization Communications, Jul 1, 2007
Tau-tubulin kinase 2 (TTBK2) is a Ser/Thr kinase that putatively phosphorylates residues Ser208 a... more Tau-tubulin kinase 2 (TTBK2) is a Ser/Thr kinase that putatively phosphorylates residues Ser208 and Ser210 (numbered according to a 441-residue human tau isoform) in tau protein. Functional analyses revealed that a recombinant kinase domain (residues 1–331) of human TTBK2 expressed in insect cells with a baculovirus overexpression system retains kinase activity for tau protein. The kinase domain of TTBK2 was crystallized using the hanging-drop vapour-diffusion method. The crystals belong to space group P212121, with unit-cell parameters a = 55.6, b = 113.7, c = 117.3 Å, α = β = γ = 90.0°. Diffraction data were collected to 2.9 Å resolution using synchrotron radiation at BL24XU of SPring-8.
Chemical Physics Letters, 1998
It is demonstrated that the Van der Waals loop appearing in the computer simulations almost vanis... more It is demonstrated that the Van der Waals loop appearing in the computer simulations almost vanishes by modifying the shape of the simulation cell even when small size systems are treated. After a long molecular dynamics simulation, it was found that the complete phase separation into vapor and liquid took place in the unstable region. The surface free energy of the interface between the liquid and vapor phases is suggested to be a major reason why the artificial loop has been observed in molecular dynamics simulations. We show that the loop depth diminishes as the box ratio of the simulation cell is enlarged.
Idiopathic interstitial fibrosis (IPF) is a chronic, usually fatal lung disease of unknown etiolo... more Idiopathic interstitial fibrosis (IPF) is a chronic, usually fatal lung disease of unknown etiology. There are few specific therapies for acute exacerbation of IPF and factors predicting the onset or severity of this syndrome are not clearly understood. A neutrophil elastase inhibitor, sivelestat (ONO-5046) has been commercially available in Japan since 2002. This inhibitor has a potent effect in the treatment of ALI/ARDS. To evaluate the outcome of patients with acute exacerbation of IPF treated with sivelestat and estimate prognostic factors, we investigated 10 patients with acute exacerbation of IPF who were intubated and mechanically ventilated. We analyzed the outcome of patients with acute exacerbation of IPF until day 180 and measured the P/F ratio, PEEP levels, the values of peripheral white blood cell number, and C-reactive protein (CRP) on day 0, 3, 7 after admission. Serum KL-6 and surfactant protein D (SP-D) concentration on day 0 were also analyzed. All patients were treated with sivelestat and methylprednisolone (mPSL) pulse therapy for 3 days from day 0 and maintenance therapy with prednisone (0.5 mg/kg/day) were continued. Of the 10 patients. 4 patients had survived (40%) and 6 patients had died (60%) at day 180 from the onset of acute exacerbation of IPF. In survivors, P/F ratio, PEEP levels, and CRP values significantly improved on day 7 (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.05). Serum KL-6 and SP-D were lower in survivors on day 0 (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.05). Taken together, serum KL-6 and SP-D may prove valuable as biochemical markers of prognosis in acute exacerbation of IPF. Sivelestat may have potential in the treatment of acute exacerbation of IPF.
Gan to Kagaku Ryoho Cancer Chemotherapy, May 1, 2006
The objective of this study was to evaluate the efficacy and toxicity of carboplatin plus weekly ... more The objective of this study was to evaluate the efficacy and toxicity of carboplatin plus weekly paclitaxel as first-line therapy in patients with advanced non-small cell lung cancer (NSCLC). Forty-nine patients were analyzed retrospectively. Every 4 weeks patients received 70 mg/m(2)paclitaxel on days 1, 8, and 15, and AUC 5-6 carboplatin on day 1. A median of four cycles (range, 1-7) was administered. Twenty-four patients had a partial response, and the overall response rate was 48.9%. The median survival time was 12.8 months and the 1-year survival was 50.7%. Overall toxicities were mild. The most common toxicity was neutropenia, grade 3/4 in 32% of the patients. Grade 3/4 hematologic toxicities included anemia (16%) and thrombocytopenia (8%). Grade 3/4 non-hematologic toxicities included febrile neutropenia (2%), pneumonia (10%) and interstitial pneumonia (2%). Grade 2 peripheral neuropathy was seen in one patient (2%). These results demonstrate that this regimen is an active and tolerable treatment for patients with advanced NSCLC. It is suggested that this weekly regimen should be considered as one of the standard therapies for future chemotherapy in advanced NSCLC.
Electrochimica Acta, 2008
The stabilization of superprotonic phase in neat CsH2PO4 and CsH2PO4/SiO2 composites as well as t... more The stabilization of superprotonic phase in neat CsH2PO4 and CsH2PO4/SiO2 composites as well as the anomalous phase transformation with a large hysteresis was investigated through proton conductivity, thermal analysis and Raman spectroscopy. The reversibility of the transition to the superprotonic phase and the phase transformation between monoclinic phase and cubic phase in neat CsH2PO4 at around Tc=230°C was confirmed under