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Biomedical subjects

H Takano

Publications and source records attributed to H Takano.

At least 217 records · Page 12Linked to original sources

Characterization of rbcL group IA introns from two colonial volvocalean species (Chlorophyceae).

Group I introns were reported for the first time in the large subunit of Rubisco (rbcL) genes, using two colonial green algae, Pleodorina californica and Gonium multicoccum (Volvocales). The rbcL gene of P. californica contained an intron (PIC intron) of 1320 bp harboring an open reading frame (ORF). The G. multicoccum rbcL gene had two ORF-lacking introns of 549 (GM1 intron) and 295 (GM2 intron) base pairs. Based on the conserved nucleotide sequences of the secondary structure, the PIC and GM1 introns were assigned to group IA2 whereas the GM2 intron belonged to group IA1. Southern hybridization analyses of nuclear and chloroplast DNAs indicated that such intron-containing rbcL genes are located in the chloroplast genome. Sequencing RNAs from the two algae revealed that these introns are spliced out during mRNA maturation. In addition, the PIC and GM1 introns were inserted in the same position of the rbcL exons, and phylogenetic analysis of group IA introns indicated a close phylogenetic relationship between the PIC and GM1 introns within the lineage of bacteriophage group IA2 introns. However, P. californica and G. multicoccum occupy distinct clades in the phylogenetic trees of the colonial Volvocales, and the majority of other colonial volvocalean species do not have such introns in the rbcL genes. Therefore, these introns might have been recently inserted in the rbcL genes independently by horizontal transmission by viruses or bacteriophage.

Amino Acid Sequence↗

Suppression of aggregate formation and apoptosis by transglutaminase inhibitors in cells expressing truncated DRPLA protein with an expanded polyglutamine stretch.

To elucidate the molecular mechanisms whereby expanded polyglutamine stretches elicit a gain of toxic function, we expressed full-length and truncated DRPLA (dentatorubral-pallidoluysian atrophy) cDNAs with or without expanded CAG repeats in COS-7 cells. We found that truncated DRPLA proteins containing an expanded polyglutamine stretch form filamentous peri- and intranuclear aggregates and undergo apoptosis. The apoptotic cell death was partially suppressed by the transglutaminase inhibitors cystamine and monodansyl cadaverine (but not putrescine), suggesting involvement of a transglutaminase reaction and providing a potential basis for the development of therapeutic measures for CAG-repeat expansion diseases.

Animals↗

Recurrence with histological transformation 40 days after autologous peripheral blood stem cell transplantation (APBSCT) for cutaneous CD30-negative large T cell lymphoma.

Localized cutaneous nontender nodules appeared on the back of a 52-year-old Japanese woman. Skin biopsy revealed atypical large T-lymphocytes infiltrating the dermis. CD30 staining was negative in tumor cells. The diagnosis was CD30-negative cutaneous large T cell lymphoma. There was no evidence of peripheral lymphadenopathy or bone marrow involvement. Six cycles of induction chemotherapy were administered and a complete clinical remission (CCR) was attained. Local irradiation was not given. As the clinical course of CD30-negative cutaneous large T cell lymphoma is recurrent and often incurable with conventional chemoradiotherapy, she received high-dose chemotherapy without total body irradiation (TBI) followed by unpurged autologous peripheral blood stem cell transplantation (APBSCT). A relapse in the skin followed 40 days after APBSCT, but tumor cells transformed into a CD30-positive anaplastic large cell lymphoma (ALCL). We question the need for TBI in conditioning and for purged stem cells for APBSCT in patients with high risk cutaneous lymphomas.

Antineoplastic Combined Chemotherapy Protocols↗

Development of a flow estimation and control system of an implantable centrifugal blood pump for circulatory assist.

A bypass flow rate estimation and control system (BECS) for an implantable centrifugal blood pump (ICBP) has been developed in our institute. The estimated flow rate (EF) of the ICBP was derived from the electric power consumption, the rotating speed of a motor, and the blood viscosity presumed by the hematocrit and body temperature. The error in the EF was 0.5 +/- 0.4 L/min in in vivo experiments for 40 days. The rotating speed of the motor was controlled automatically every 200 ms to bring the EF in accord with the desired flow rate (DF). The reactivity and accuracy of the BECS were investigated in in vitro and in vivo experiments. The ICBP was operated by the BECS in a mock circuit in parallel with a pulsatile ventricular assist device (PVAD) to simulate left heart bypass. The reactivity was evaluated by changing the DF from 7 L/min to 5 L/min at an afterload of 160/97 mm Hg. To evaluate the accuracy of the BECS, the ICBP was driven under the aortic pressure of 110/85 mm Hg in the abdominal wall of an adult goat (70 kg). The DF was set at 5 L/min for 4 min for the goat in an awake condition. It took 13 s to change the flow rate in the in vitro experiment. The measured flow rate (MF) was maintained at 5.0 +/- 0.2 L/min by the BECS in vivo. In conclusion, the BECS has moderate reactivity and accuracy.

Abdominal Muscles↗

Intrathoracic and intraabdominal wall implantation of a centrifugal blood pump for circulatory assist.

An implantable centrifugal pump (ICP) 320 ml in volume and 830 g in weight has been developed for prolonged circulatory assist. The antithrombogenicity of the ICP is provided by a balancing hole in the center of the impeller. The watertightness and histocompatibility of the ICP are supported by its silicone ring seal and its casing of titanium and acrylic resin, respectively. The total efficiency of the ICP was 30% at a 5 L/min flow rate and a 100 mm Hg head. The heat generation, watertightness, and anatomical fitting of the ICP were assessed in an intrathoracic implantation in a goat (66 kg) and in an intraabdominal wall implantation in a goat (70 kg). Warfarin was given for anticoagulation in each experiment to keep the prothrombin time around 1.7 times that of the control. The temperatures of the pump surface, the pleura, and the room were measured every 3 h. Anatomical fitting was evaluated by pathological observation after the termination of the experiment. The ICP could run for 40 days in the chest cavity and for 11 days in the abdominal wall. The temperature of the motor remained about 1.8 degrees C higher than the reference in both experiments. The ICP was completely covered by a layer of smooth fibrous tissue. The moisture content of the seals remained normal. Although a small amount of atelectasis was found in the lingula, neither lung adhesion nor necrotic change of the chest wall was observed. The inflammation of the surrounding tissue including foreign body reaction and thermal burn was minimal. In conclusion, the ICP has satisfied in vivo testing of its watertightness, exothermicity, and anatomical fitting.

Abdominal Muscles↗

Prolonged nonpulsatile left heart bypass with reduced systemic pulse pressure causes morphological changes in the aortic wall.

We investigated the morphological changes in the aorta due to reduced systemic pulse pressure in prolonged nonpulsatile left heart bypass (LHB). Nineteen adult goats were divided into 3 groups, the nonpulsatile group in which nonpulsatile LHB was conducted, the pulsatile group in which pulsatile LHB was conducted, and the control group used as the normal control. The average aortic pulse pressures were 12, 47, and 37 mm Hg, respectively. The descending aorta was subjected to morphological examination. In the nonpulsatile group, the wall was significantly thinner, and the volume ratio of smooth muscle cells (SMCs) was much lower. In terms of the SMC type classification, the proportion of SMCs with low activity and low contractility was higher, and the cell density of the SMCs was increased compared to those in the other groups. These results indicate that prolonged nonpulsatile LHB causes morphological atrophic changes in the aorta.

Animals↗

Development of design methods of a centrifugal blood pump with in vitro tests, flow visualization, and computational fluid dynamics: results in hemolysis tests.

There are few established engineering guidelines aimed at reducing hemolysis for the design of centrifugal blood pumps. In this study, a fluid dynamic approach was applied to investigate hemolysis in centrifugal pumps. Three different strategies were integrated to examine the relationship between hemolysis and flow patterns. Hemolytic performances were evaluated in in vitro tests and compared with the flow patterns analyzed by flow visualization and computational fluid dynamic (CFD). Then our group tried to establish engineering guidelines to reduce hemolysis in the development of centrifugal blood pumps. The commercially available Nikkiso centrifugal blood pump (HPM-15) was used as a standard, and the dimensions of 2 types of gaps between the impeller and the casing, the axial and the radial gap, were varied. Four impellers with different vane outlet angles were also prepared and tested. Representative results of the hemolysis tests were as follows: The axial gaps of 0.5, 1.0, and 1.5 mm resulted in normalized index of hemolysis (NIH) values of 0.0028, 0.0013 and 0.0008 g/100 L, respectively. The radial gaps of 0.5 and 1.5 mm resulted in NIH values of 0.0012 and 0.0008 g/100 L, respectively. The backward type vane and the standard one resulted in NIH values of 0.0013 and 0.0002 g/100 L, respectively. These results revealed that small gaps led to more hemolysis and that the backward type vane caused more hemolysis. Therefore, the design parameters of centrifugal blood pumps could affect their hemolytic performances. In flow visualization tests, vortices around the impeller outer tip and tongue region were observed, and their patterns varied with the dimensions of the gaps. CFD analysis also predicted high shear stress consistent with the results of the hemolysis tests. Further investigation of the regional flow patterns is needed to discuss the cause of the hemolysis in centrifugal blood pumps.

Animals↗

Hemodynamics of a simulation of the vertebrobasilar system using silicone tube.

We investigated the hemodynamics of the vertebrobasilar system (VBS) using a simulation model tube made of silicone which had different diameters between the bilateral vertebral artery (VA) ducts (stenotic and normal VA ducts). Using the ultrasonic Doppler method. the laterality index (L.I.) of the flow velocity in the VA duct was 32.88%. The flow volume of the anterior inferior cerebellar artery duct and the posterior inferior cerebellar artery duct also had significant laterality. By investigating the effects of the rotatory pulse rate and fluid viscosity, a maximal decrease to below 40-50% of the flow volume of the branches, and to below 71.93% in the mean flow velocity of the basilar artery (BA) duct (BA duct) were observed. and the maximum L.I. increased to 43.15%. When the unilateral stenotic VA duct was occluded by clamping (clamping occlusion), the flow volume profiles of the branches were the same as without clamping occlusion. The L.I. showed no significant changes and the maximal decrease in the mean flow velocity of the BA duct was 68.61%. Using the laser Doppler method, the flow velocity distribution of the BA duct was shifted towards the side of the stenotic VA duct. These results suggest that the rheological dynamics in the main vessels can certainly reflect the posterior circulatory dynamics, and that modulating factors also aggravate the hemodynamics of the VBS with this disorder.

Arteries↗

Close associations between prevalences of dominantly inherited spinocerebellar ataxias with CAG-repeat expansions and frequencies of large normal CAG alleles in Japanese and Caucasian populations.

To test the hypothesis that the frequencies of normal alleles (ANs) with a relatively large number of CAG repeats (large ANs) are related to the prevalences of the dominant spinocerebellar ataxias (SCAs)-SCA types 1, 2, 3 (Machado-Joseph disease), 6, and dentatorubral-pallidoluysian atrophy (DRPLA)-we investigated the relative prevalences of these diseases in 202 Japanese and 177 Caucasian families and distributions of the number of CAG repeats of ANs at these disease loci in normal individuals in each population. The relative prevalences of SCA1 and SCA2 were significantly higher in Caucasian pedigrees (15% and 14%, respectively) than in Japanese pedigrees (3% and 5%, respectively), corresponding to the observation that the frequencies of large ANs of SCA1 (alleles >30 repeats) and of SCA2 (alleles >22 repeats) were significantly higher in Caucasians than in Japanese. The relative prevalences of MJD/SCA3, SCA6, and DRPLA were significantly higher in Japanese pedigrees (43%, 11%, and 20%, respectively) than in Caucasian pedigrees (30%, 5%, and 0%, respectively), corresponding to the observation that the frequencies of large ANs of MJD/SCA3 (>27 repeats), SCA6 (>13 repeats), and DRPLA (>17 repeats) were significantly higher in Japanese than in Caucasians. The close correlations of the relative prevalences of the dominant SCAs with the distributions of large ANs strongly support the assumption that large ANs contribute to generation of expanded alleles (AEs) and the relative prevalences of the dominant SCAs.

Asian People↗

The Rho family G proteins play a critical role in muscle differentiation.

The Rho family GTP-binding proteins play a critical role in a variety of cytoskeleton-dependent cell functions. In this study, we examined the role of Rho family G proteins in muscle differentiation. Dominant negative forms of Rho family proteins and RhoGDI, a GDP dissociation inhibitor, suppressed transcription of muscle-specific genes, while mutationally activated forms of Rho family proteins strongly activated their transcription. C2C12 cells overexpressing RhoGDI (C2C12RhoGDI cells) did not differentiate into myotubes, and expression levels of myogenin, MRF4, and contractile protein genes but not MyoD and myf5 genes were markedly reduced in C2C12RhoGDI cells. The promoter activity of the myogenin gene was suppressed by dominant negative mutants of Rho family proteins and was reduced in C2C12RhoGDI cells. Expression of myocyte enhancer binding factor 2 (MEF2), which has been reported to be required for the expression of the myogenin gene, was reduced at the mRNA and protein levels in C2C12RhoGDI cells. These results suggest that the Rho family proteins play a critical role in muscle differentiation, possibly by regulating the expression of the myogenin and MEF2 genes.

Actins↗

Diesel exhaust inhalation enhances airway hyperresponsiveness in mice.

BACKGROUND: Repeated intratracheal instillation of diesel exhaust particles and ovalbumin-induced airway hyperresponsiveness and airway inflammation in mice. However, the effects of daily inhalation of diesel exhaust may differ from the effects of direct instillation. METHODS: Therefore, mice were exposed to diesel exhaust by inhalation 12 h per day for 3 months. Before the diesel exhaust exposure, ovalbumin was injected intraperitoneally as a sensitization. After 3 weeks of diesel exhaust exposure, these mice were challenged with ovalbumin every 3 week thereafter. RESULTS: Diesel exhaust exposure with antigen challenge induced airway hyperresponsiveness and airway inflammation which was characterized by increased numbers of eosinophils and mast cells in lung tissue. The recruitment of inflammatory cells was accompanied by an increment in goblet cells on bronchial epithelium. Diesel exhaust exposure alone also enhanced airway hyperresponsiveness, but did not induce eosinophilic infiltration and/or an increment in goblet cells. CONCLUSION: Diesel exhaust inhalation enhanced airway hyperresponsiveness and airway inflammation caused by ovalbumin sensitization in mice.

Animals↗

Diesel exhaust enhances allergic airway inflammation and hyperresponsiveness in mice.

We previously reported that the intratracheal instillation of diesel exhaust particles enhances allergic airway inflammation and hyperresponsiveness in mice. However, it is not known whether the effects of such instillation differ from those obtained with the daily inhalation of diesel exhaust. We therefore examined whether the inhalation of diesel exhaust would also enhance allergic reactions. Mice were exposed to diesel exhaust or clean air for 5 wk. After the first week, the animals were sensitized to ovalbumin by intraperitoneal injection. At the end of the exposure period, they underwent an ovalbumin challenge. Control animals received saline instead of ovalbumin. Independently of ovalbumin sensitization, diesel exhaust caused an increase in the numbers of neutrophils and macrophages in bronchoalveolar lavage fluid, whereas a significant increase in eosinophil numbers occurred only after antigen challenge combined with diesel exhaust exposure. Furthermore, ovalbumin alone caused an increase in eosinophil numbers in lung tissue, and this was enhanced by diesel exhaust. Exposure to diesel exhaust combined with ovalbumin sensitization, but not diesel exhaust inhalation alone, enhanced the number of goblet cells in lung tissue, respiratory resistance, production of ovalbumin-specific immunoglobulin E and G1 in the serum, and expression of interleukin-5 in lung tissue.

Administration, Inhalation↗

Murine strain differences in airway inflammation caused by diesel exhaust particles.

To elucidate whether immunoglobulin (Ig) E or IgG are involved in the murine asthma model, we compared the pathogenic features of mice that were high IgG responders (C3H/He) with mice that were high IgE responders (BALB/c) after intratracheal instillation of diesel exhaust particles (DEP) and ovalbumin sensitization. Both mouse strains received DEP intratracheally once a week for 5 weeks. After the second injection of DEP, ovalbumin and aluminium hydroxide were injected intraperitoneally. After the last DEP administration, the mice were challenged by exposure to an aerosol of ovalbumin. DEP caused increased IgG1 production and airway hyperresponsiveness after ovalbumin sensitization in C3H/He mice, although IgE production did not change in either strain. Furthermore, in C3H/He mice, the number of eosinophils and goblet cells in the bronchial epithelium, and the expression of interleukin-5 and interleukin-2 were increased by DEP and ovalbumin treatments. In contrast, the pathogenic changes in BALB/c mice were weak, even though the same protocol was used. In conclusion, murine strain differences in response to air pollutants and allergens seem to be related to antigen-specific immunoglobulin G1 production and cytokine expression in the lungs.

Aerosols↗

Sporadic cases of dentatorubral-pallidoluysian atrophy associated with maternal transmission.

We report siblings, a 21-year-old woman (proband) and her 26-year-old brother, with dentatorubral-pallidoluysian atrophy (DRPLA). There was no family history of DRPLA and no clinical abnormalities in their parents, who were both above the age of 50. Analysis of the DRPLA gene of leukocytes showed CAG repeat sizes to be 64/17 in the proband, 58/20 in her brother, and 56/8 in their mother. Sporadic cases of DRPLA can occur with maternal as well as paternal transmission.

Adult↗

Electrical properties of colonic smooth muscle in spontaneously non-insulin-dependent diabetic rats.

Electrical properties of colonic smooth muscle were investigated in the Otsuka Long-Evans Tokushima Fatty (OLETF) rat, a model animal for spontaneous non-insulin-dependent diabetes mellitus (NIDDM), and the results were compared with those obtained from the Long-Evans Tokushima Otsuka (LETO) rat, a control of OLETF rat. At experiments (aged 60-80 weeks), blood glucose level was about 171 mg/dl in LETO rats and 370 mg/dl in OLETF rats. Feces in the colon were restricted to the proximal region in LETO rats and distributed widely in the whole colon in OLETF rats. In both LETO and OLETF rats, the circular smooth muscle strips of the isolated distal colon revealed two types of spontaneous electrical response, slow wave and transient hyperpolarization. The resting membrane potential was smaller in OLETF rats than in LETO rats by about 3 mV, but it was not positively related with the blood glucose level. The amplitude of hyperpolarization produced by noradrenaline (NA) was smaller in OLETF rats than in LETO rats. Transmural nerve stimulation evoked a non-adrenergic, non-cholinergic (NANC) inhibitory junction potential (i.j.p.) in both LETO and OLETF rats; the amplitude of the i.j.p. was smaller in OLETF rats than in LETO rats, while the latency of the i.j.p. was longer in OLETF rats than in LETO rats. Thus, in the distal colon, NIDDM may cause a depolarization of the membrane, an attenuation of NANC inhibitory transmission and a reduction in reactivity of adrenoceptors to NA. These results suggest that the constipation appearing with diabetes mellitus involves dysfunction of both the enteric autonomic nerves and the smooth muscles in the colon.

Adrenergic alpha-Agonists↗

Diesel exhaust particles enhance airway responsiveness following allergen exposure in mice.

We have previously reported that intratracheal instillation of diesel exhaust particles (DEP) enhances allergen-induced eosinophilic airway inflammation, local expression of interleukin-5 and granulocyte macrophage-colony stimulating factor, and allergen-specific production of IgE and IgG in mice. The present study was undertaken to elucidate the effects of DEP on airway hyperresponsiveness as another characteristic feature of allergic asthma. The animals were randomized into four experimental groups that received intratracheal instillation with vehicle, ovalbumin (OVA), DEP, or the combination of OVA and DEP on a weekly basis for 6 weeks. Respiratory resistance (Rrs) was measured 24 h after the last instillation. An increase in Rrs in animals that inhaled acetylcholine was significantly greater in the combined treatment with OVA and DEP than in the other treatments. The present study indicates that DEP can enhance airway responsiveness associated with allergen exposure, and provides experimental evidence that DEP may deteriorate the pathophysiology of allergen-related respiratory disease such as allergic asthma.

Acetylcholine↗

Advanced nasopharyngeal carcinoma treated with chemotherapy and radiotherapy: distant metastasis and local recurrence.

One hundred and twenty-nine patients with NPC treated at the Department of Radiology, Chiba University Hospital and Keio University Hospital from 1980 through 1993 were selected for this study. Forty-four patients received cisplatin (CDDP)- or carboplatin-based chemotherapy, and 58 patients received adriamycin (ADM)- and/or 5-FU-based chemotherapy. The remaining 27 patients were treated with radiotherapy alone. The median radiation dose to the nasopharyngeal region was 64 Gy, and to the initially involved cervical node, 60 Gy. The 5 year survival rates for the CDDP, the ADM/5-FU and the radiation alone groups were 61%, 47% and 42%, respectively. The cumulative incidences of local control in the CDDP, the ADM/5-FU and the radiation alone groups were 77%, 49% and 53% respectively. The CDDP group achieved the significantly better local control (CDDP vs ADM: p=0.001). The overall incidence of distant metastases was 54% in the CDDP group. On the other hand, it was 24% in the ADM/5-FU group and 22% in the radiation alone group (CDDP vs ADM: p=0.048). While the locoregional control rate was significantly better in the CDDP given group, more distant metastases were seen in this group.

Adolescent↗