Biomedical subjects

Hajime Sato

Publications and source records attributed to Hajime Sato.

At least 19 recordsLinked to original sources

PubMed2007

Involvement of persistent Na+ current in spike initiation in primary sensory neurons of the rat mesencephalic trigeminal nucleus.

It was recently shown that the persistent Na(+) current (I(NaP)) is generated in the proximal axon in response to somatic depolarization in neocortical pyramidal neurons, although the involvement of I(NaP) in spike initiation is still unclear. Here we show a potential role of I(NaP) in spike initiation of primary sensory neurons in the mesencephalic trigeminal nucleus (MTN) that display a backpropagation of the spike initiated in the stem axon toward the soma in response to soma depolarization. Riluzole (10 muM) and tetrodotoxin (TTX, 10 nM) caused an activation delay or a stepwise increase in the threshold for evoking soma spikes (S-spikes) without affecting the spike itself. Simultaneous patch-clamp recordings from the soma and axon hillock (AH) revealed that bath application of 50 nM TTX increased the delay in spike activation in response to soma depolarization, leaving the spike-backpropagation time from the AH to soma unchanged. This indicates that the increase in activation delay occurred in the stem axon. Furthermore, under a decreasing intracellular concentration gradient of QX-314 from the soma to AH created by QX-314-containing and QX-314-free patch pipettes, the amplitude and maximum rate of rise (MRR) of AH-spikes decreased with an increase in the activation delay following repetition of current-pulse injections, whereas S-spikes displayed decreases of considerably lesser degree in amplitude and MRR. This suggests that compared to S-spikes, AH-spikes more accurately reflect the attenuation of axonal spike by QX-314, consistent with the nature of spike backpropagation. These observations strongly suggest that low-voltage-activated I(NaP) is involved in spike initiation in the stem axon of MTN neurons.

4-Aminopyridine↗

PubMed2006

Screening of the MERTK gene for mutations in Japanese patients with autosomal recessive retinitis pigmentosa.

PURPOSE: To determine whether mutations in the MERTK gene are present in Japanese patients with autosomal recessive retinitis pigmentosa (arRP). METHODS: The coding sequence of all 19 exons and the adjacent flanking intron sequences of the MERTK gene were directly sequenced in 96 unrelated Japanese patients with arRP. RESULTS: Seventeen sequence variants were found; six missense changes, three isocoding changes, and eight intron changes were also observed. One arRP patient had a novel homozygous Leu12Pro missense mutation in the MERTK gene. CONCLUSIONS: Mutations in the MERTK gene are relatively rare in Japanese patients with arRP.

Asian People↗

PubMed2006

Two opposing roles of 4-AP-sensitive K+ current in initiation and invasion of spikes in rat mesencephalic trigeminal neurons.

The axon initial segment plays important roles in spike initiation and invasion of axonal spikes into the soma. Among primary sensory neurons, those in the mesencephalic trigeminal nucleus (MTN) are exceptional in their ability to initiate soma spikes (S-spikes) in response to synaptic inputs, consequently displaying two kinds of S-spikes, one caused by invasion of an axonal spike arising from the sensory receptor and the other initiated by somatic inputs. We investigated where spikes are initiated in such MTN neurons and whether there are any differences between the two kinds of S-spikes. Simultaneous patch-clamp recordings from the soma and axon hillock revealed a spike-backpropagation from the spike-initiation site in the stem axon to the soma in response to 1-ms somatic current pulse, which disclosed the delayed emergence of S-spikes after the current-pulse offset. These initiated S-spikes were smaller in amplitude than S-spikes generated by stimulation of the stem axon; however, 4-AP (< or =0.5 mM) eliminated the amplitude difference. Furthermore, 4-AP dramatically shortened the delay in spike initiation without affecting the spike-backpropagation time in the stem axon, whereas it substantially prolonged the refractory period of S-spikes arising from axonal-spike invasion without significantly affecting that of presumed axonal spikes. These observations suggest that 4-AP-sensitive K(+) currents exert two opposing effects on S-spikes depending on their origins: suppression of spike initiation and facilitation of axonal-spike invasion at higher frequencies. Consistent with these findings, strong immunoreactivities for Kv1.1 and Kv1.6, among 4-AP-sensitive and low-voltage-activated Kv1 family examined, were detected in the soma but not in the stem axon of MTN neurons.

4-Aminopyridine↗

PubMed2006

Collagen synthesis is required for ascorbic acid-enhanced differentiation of mouse embryonic stem cells into cardiomyocytes.

Ascorbic acid has been reported to promote the differentiation of embryonic stem (ES) cells into cardiomyocytes; however, the specific functions of ascorbic acid have not been defined. A stable form of ascorbic acid, namely, l-ascorbic acid 2-phosphate (A2-P), significantly enhanced cardiac differentiation; this was assessed by spontaneous beating of cardiomyocytes and expression of cardiac-specific markers obtained from mouse ES cells. This effect of ascorbic acid was observed only when A2-P was present during the early phase of differentiation. Treatment with two types of collagen synthesis inhibitors, l-2-azetidine carboxylic acid and cis-4-hydroxy-d-proline, significantly inhibited the A2-P-enhanced cardiac differentiation, whereas treatment with the antioxidant N-acetyl cysteine showed no effect. These findings demonstrated that ascorbic acid enhances differentiation of ES cells into cardiomyocytes through collagen synthesis and suggest its potential in the modification of cardiac differentiation of ES cells.

Animals↗

PubMed2006

Public, experts, and acceptance of advanced medical technologies: the case of organ transplant and gene therapy in Japan.

In 1997, after long social debates, the Japanese government enacted a law on organ transplantation from brain-dead bodies. Since 1993, on gene therapy, administrative agencies have issued a series of guidelines. This study seeks to elucidate when people became aware of the issues and when they formed their opinions on organ transplant and gene therapy. At the same time, it aims to examine at which point in time experts, those in university ethical committees and in academic societies, consider these technologies became accepted among the public. A self-administered questionnaire was sent by mail to a stratified random sampling of 3,000 people nationwide in Japan. Another questionnaire was sent both to the member societies of the Japanese Association of Medical Sciences and to the ethical committees of all the medical schools in Japan. Results of the surveys indicated that many of the public remained undecided on the desirability of organ transplant or gene therapy at the time of enactment of official guidelines. A substantial part of them formed their opinions in subsequent periods, especially around the time of first implementation and thereafter. Experts of the academic societies and of the university ethical committees regarded the time of implementation as an important factor in the acceptance of the technologies in society. Since many people formed their opinion during the period of technological implementation, communications efforts to facilitate public understanding of science and technology, as well as to advance practical discussion on policy alternatives in this period can play a key role in determining the fate of technological innovation and ethical debates in medicine.

Expert Testimony↗

PubMed2006

Hypothermia of 8 degrees C protects cultured retinal pigment epithelial cells and retinal ganglion cells against trypan blue toxicity.

PURPOSE: To determine whether hypothermia of 8 degrees C can protect cultured human retinal pigment epithelial (ARPE-19) cells and rat retinal ganglion cells (RGC-5) against trypan blue (TB) toxicity. DESIGN: Laboratory investigation. METHODS: ARPE-19 cells and RGC-5 were exposed to balanced salt solution as controls, and 0.05% and 0.5% TB at 37 degrees C, and at 8 degrees C for one minute. The percentage of surviving cells was determined by the resazurin test. RESULTS: TB induced a statistically significant decrease in the percentage of ARPE-19 cells surviving at 0.5% TB at 37 degrees C (P < .01). Conversely, TB induced a statistically significant decrease in the percentage of RGC-5 surviving at all conditions except for 0.05% TB at 8 degrees C (0.05% 37 degrees C; P < .05, 0.5% 37 degrees C and 8 degrees C; P < .01). CONCLUSIONS: These results indicate that reducing the temperature to 8 degrees C has a protective effect against the TB toxicity for ARPE-19 cells and RGC-5 in culture.

Animals↗

PubMed2006

Establishing interspecific mosaic genome lines between Drosophila ananassae and Drosophila pallidosa by means of parthenogenesis.

Strong sexual isolation exists between the closely related species Drosophila ananassae and D. pallidosa, but there is no obvious post-mating isolation; both sexes of the hybrids and their descendants appear to be completely viable and fertile. Strains exhibiting parthenogenesis have been derived from wild populations of both species. We intercrossed such strains and established iso-female lines after the second generation of parthenogenesis. These lines are clones, carrying homozygous chromosomes that are interspecific recombinants. We established 266 such isogenic lines and determined their genetic constitution by using chromosomal and molecular markers. Strong pseudo-linkage was seen between loci on the left arm of chromosome 2 and on the right arm of chromosome 3; the frequency of inheriting the two chromosome regions from the same species was significantly larger than expected. One possible cause of pseudo-linkage is female meiotic bias, so that chromosomes of the same species origin tend to be distributed to the same gamete. But this possibility is ruled out; backcross analysis indicated that the two chromosome regions segregated independently in female hybrids. The remaining possibility is elimination of low-fitness flies carrying the two chromosome regions from different species. Thus, genetic incompatibility was detected in the species pair for which no hybrid breakdown had previously been indicated. The 'interspecific mosaic genome' lines reported here will be useful for future research to identify genes involved in speciation and phenotypic evolution.

Animals↗

PubMed2006

Hypothermia protects cultured human retinal pigment epithelial cells against trypan blue toxicity.

PURPOSE: To determine whether trypan blue (TB) is toxic to cultured human retinal pigment epithelial (ARPE-19) cells, and whether hypothermia can protect ARPE-19 cells against TB toxicity. METHODS: ARPE-19 cells were cultured and exposed to balanced salt solution as a control, while other cells were exposed to 0.05, 0.2, and 0.5% TB dye at 37 and 4 degrees C for 5 and 30 min. The percentage of ARPE-19 cells that survived was determined by resazurin 1 day after the exposure. RESULTS: A statistically significant decrease in the percentage of ARPE-19 cells surviving was found after exposure to 0.2 and 0.5% TB at any temperature or for any exposure duration (p < 0.01). The percentage of RPE cells surviving at 0.05% was not significantly different from that of controls except for a 30-min exposure at 37 degrees C. The percentage of cells surviving at 4 degrees C for a 5-min exposure to 0.5% TB and a 30-min exposure to 0.2 and 0.5% was significantly higher than that at 37 degrees C under each condition (p < 0.01 for all). CONCLUSIONS: These results indicate that TB is toxic to human RPE cells, and the toxicity is dose- and exposure duration-dependent. Exposing the cells at 4 degrees C had a protective effect against higher concentrations or longer exposure durations of TB compared to exposure at 37 degrees C.

Cell Count↗

PubMed2006

Chronic colitis promotes tumor development.

Patients with chronic ulcerative colitis have a significantly increased risk of colorectal cancer development. This study was aimed at clarifying whether colitis promotes tumor development or not. A dose of 200 mg/kg body weight 1,2-dimethylhydrazine was given to male Wistar rats. Four weeks later, 5% acetic acid (colitis group) or 0.9% saline (control group) was administered intrarectally once a week for 12 weeks and the rats were sacrificed after 27 weeks of dimethylhydrazine injection. Macroscopic lesions (ML) were more frequently detected in the colitis group than in the control group without statistical significance. However, the number of ML per rat with ML was largest in the colitis group (4.50 vs. 1.33; p=0.039). Eleven of 13 tumors were sessile in the colitis group, while three of five were pedunculated in the control group (p=0.044). All ML of 3 mm or more in diameter in the control group were intramucosal well-differentiated tumors. In the colitis group, 4 of 13 tumors were poorly or moderately differentiated or mucinous carcinomas, and 11 of 13 invaded the submucosal layer or deeper (p=0.003). The number of aberrant crypt foci per rat was smaller in the colitis group than in the control group. The number of crypt orifices was larger in the colitis group than in the control group (23.6 vs. 8.8: p<0.001). Significantly higher proliferative activity of normal-appearing mucosa was noted in the colitis group in all three parts of the colon. Colitis is suggested to promote colonic tumor development.

1,2-Dimethylhydrazine↗

PubMed2006

Appraisal of the policymaking process in Japan for gene therapy: results of national surveys of academic societies, hospitals, and medical schools.

BACKGROUND: Since 1993, government agencies in Japan have introduced a series of guidelines for gene therapy clinical trials. Appraisals of these guidelines were obtained from academic societies, institutional review boards (IRBs) of hospitals, and ethics committees (ECs) at medical schools nationwide. MATERIAL/METHODS: Using data from a large-scale national opinion survey, this study evaluates the experts' appraisals of the contents of these official guidelines in Japan and the process of their development. RESULTS: 26.3% of the respondents from academic societies and 39.3% of those from university ECs gave positive appraisals of the speediness of the decision process for the 1994 guidelines. Appraisals of speediness improved for the 2002 guidelines. Concerning the clarity of the 1994 guidelines, the proportion of positive appraisals was slightly smaller than negative appraisals among academic societies and hospital IRBs, though the majority of university ECs gave positive ratings. The 2002 guidelines were appraised significantly more positively than the 1994 guidelines. Information received after the decision was consistently rated better than the information before the decision. All groups reported that the opinions of patients and those of citizens were less adequately considered than were the opinions of experts. A majority of respondents rated information disclosure as important for future agendas. CONCLUSIONS: Clarity of the guidelines could be improved by revision. More information disclosure was considered desirable, especially information available before decisions are made. Incorporation of patients and citizens in policymaking is an important future goal.

Clinical Trials as Topic↗

PubMed2005

Lead and other trace metals in preeclampsia: a case-control study in Tehran, Iran.

To assess the effects of environmental exposures to trace metals on the incidence of preeclampsia, concentrations of lead (Pb), antimony (Sb), manganese (Mn), mercury, cadmium, cobalt and zinc in umbilical cord blood (UCB) and mother whole blood (MWB) were measured in 396 postpartum women without occupational exposure to metals in Tehran, Iran, using inductively coupled plasma mass spectrometry. Mother's ages ranged from 15 to 49 (mean 27) years. Preeclampsia was diagnosed in 31 subjects (7.8%). Levels of Pb, Sb and Mn in UCB were significantly higher in preeclampsia cases [mean+/-SD of 4.30+/-2.49 microg/dl, 4.16+/-2.73 and 46.87+/-15.03 microg/l, respectively] than in controls [3.52+/-2.09 microg/dl, 3.17+/-2.68 and 40.32+/-15.19 microg/l, respectively] (P<0.05). The logistic regression analysis revealed that one unit increase in the common logarithms of UCB concentration of Pb, Sb or Mn led to increase in the risk of preeclampsia several-fold; unit risks (95% CI) were 12.96 (1.57-107.03), 6.11 (1.11-33.53) and 34.2 (1.81-648.04) for Pb, Sb and Mn, respectively (P<0.05). These findings suggest that environmental exposure to Pb, Sb and Mn may increase the risk of preeclampsia in women without occupational exposure; levels of metals in UCB to be sensitive indicators of female reproductive toxicity as compared with those in mother MWB. Further studies are necessary to confirm these findings, especially on Sb and Mn.

Adolescent↗

PubMed2005

Statistical comparison of dog and cat guard hairs using numerical morphology.

Numerical features obtained from the guard hairs of dogs and cats (total 300 hairs per dog or cat) were statistically compared, in an attempt to discriminate between them. Using hairs from each of five mongrel dogs and cats, eight measurements (length (Len), maximum width (MaxWid), cross sectional maximum diameter, cross sectional minimum diameter, cuticular thickness of the cross section and three scale counts per 100 microm length (observed at three positions: distal third (disSC), middle (midSC) and the proximal third (proSC) portions) and five indexes (hair width index (HWI), medulla index (MI), hair index, cuticle index and the difference in scale counts between the distal and proximal parts (defSC)) were examined. The range for each numerical feature overlapped each other extensively, and none of the features permitted a discrimination between dog and cat hairs, based on the values obtained. However, 12 numerical features, except for the midSC, showed a statistically significant difference between dog and cat hairs, as evidenced by a t-test. For the purpose of comprehensively comparing numerical features and statistically discriminating between dog and cat hairs, a discriminant analysis between the two were carried out using a multiple regression analysis. Four types of discriminant functions produced by combining over five numerical features were examined. Dog and cat hairs could clearly be discriminated using any of the discriminant functions. Species discrimination using the discriminant function permitted the species of a dog or cat to be determined, based on the overall morphologies of various numerical features. When experimentally collected test samples were investigated using the discriminant function using Combination-2, consisting of eight numerical features (Len, MaxWid, MI, HWI, disSC, midSC, proSC and defSC), all 10 cat hairs were correctly determined to be cat hair and 22 of 23 dog hairs were correctly identified. This discriminant function produced good results for species discrimination between dog and cat hairs.

Animals↗

PubMed2005

Comparison of neurocognitive results after coronary artery bypass grafting and thoracic aortic surgery using retrograde cerebral perfusion.

OBJECTIVE: Retrograde cerebral perfusion (RCP) is used as an adjunctive method to hypothermic circulatory arrest to enhance cerebral protection in patients undergoing thoracic aortic surgery. It remains unclear whether RCP provides improved neurological and neuropsychological outcome. METHODS: Forty-six patients undergoing thoracic aortic surgery using RCP, and 28 undergoing coronary artery bypass grafting (CABG; n = 28) with CPB, were enrolled in the study. Patients receiving RCP were subdivided into two groups, those with less than 60 min of RCP (S-RCP; n = 27) and with 60 min or more (L-RCP; n = 19). The patients' neurocognitive state was assessed by the revised Wechsler Adult Intelligence Scale a few days before operation, at 2-3 weeks and 4-6 months after operation. RESULTS: There were no stroke, seizure, and hospital mortality in either group. Significant decline between baseline and early scores were seen in three subtests (digit span, arithmetic, and picture completion) for S-RCP and four (digit span, arithmetic, picture completion, and picture arrangement) for L-RCP. Significant decline between baseline and late scores were seen in one subtest (arithmetic) for S-RCP, four (digit span, arithmetic, picture completion, and picture arrangement) for L-RCP, and one (object assembly) for CABG. The mean change of scores for one late test (digit symbol) was significantly lower in S-RCP than in CABG. The mean change of scores for three early tests (digit span, vocabulary, and picture arrangement) and four late tests (information, digit span, picture completion, and picture arrangement) were significantly lower in L-RCP than in CABG. Stepwise logistic regression analysis disclosed that, after considering the other variables, significant difference in test score changes were observed between CABG and L-RCP for two early tests (picture completion and digit symbol) as well as for three late tests (digit span, similarities, and picture completion). None of test score changes showed significant difference between CABG and S-RCP. CONCLUSIONS: The neurocognitive outcome in patients undergoing RCP less than 60 min were comparable with patients undergoing CABG without circulatory arrest. Prolonged RCP of 60 min or more in patients undergoing surgery of the thoracic aorta was associated with postoperative neurocognitive impairment.

Adult↗

PubMed2005

Termination of the leprosy isolation policy in the US and Japan : Science, policy changes, and the garbage can model.

BACKGROUND: In both the US and Japan, the patient isolation policy for leprosy /Hansen's disease (HD) was preserved along with the isolation facilities, long after it had been proven to be scientifically unnecessary. This delayed policy termination caused a deprivation of civil liberties of the involuntarily confined patients, the fostering of social stigmas attached to the disease, and an inefficient use of health resources. This article seeks to elucidate the political process which hindered timely policy changes congruent with scientific advances. METHODS: Examination of historical materials, supplemented by personal interviews. The role that science played in the process of policy making was scrutinized with particular reference to the Garbage Can model. RESULTS: From the vantage of history, science remained instrumental in all period in the sense that it was not the primary objective for which policy change was discussed or intended, nor was it the principal driving force for policy change. When the argument arose, scientific arguments were employed to justify the patient isolation policy. However, in the early post-WWII period, issues were foregrounded and agendas were set as the inadvertent result of administrative reforms. Subsequently, scientific developments were more or less ignored due to concern about adverse policy outcomes. Finally, in the 1980s and 1990s, scientific arguments were used instrumentally to argue against isolation and for the termination of residential care. CONCLUSION: Contrary to public expectations, health policy is not always rational and scientifically justified. In the process of policy making, the role of science can be limited and instrumental. Policy change may require the opening of policy windows, as a result of convergence of the problem, policy, and political streams, by effective exercise of leadership. Scientists and policymakers should be attentive enough to the political context of policies.

Journal Article↗

PubMed2005

An unambiguous assignment method by 2D selective-TOCSY-HSQC and selective-TOCSY-DQFCOSY and structural analysis by selective-TOCSY-NOESY experiments of a biantennary undecasaccharide.

In this paper we present a newly developed 2D selective-TOCSY-HSQC experiment for unambiguous assignment of individual sugar components of a biantennary undecasaccharide. The correlation signals between the protons and carbons of a selectively excited sugar component in the undecasaccharide were observed in a 2D selective-TOCSY-HSQC experiment. The network of proton signals of this sugar was observed in a 2D selective-TOCSY-DQFCOSY experiment. These two experiments enabled us to perform unambiguous sequential assignment of both protons and carbons of the individual sugar components in the undecasaccharide. In addition, a three-dimensional structural analysis was performed by a 2D selective-TOCSY-NOESY experiment, which clearly distinguishes between inter-sugar and intra-sugar ring NOE signals.

Carbohydrate Conformation↗

PubMed2005

Public appraisal of government efforts and participation intent in medico-ethical policymaking in Japan: a large scale national survey concerning brain death and organ transplant.

BACKGROUND: Public satisfaction with policy process influences the legitimacy and acceptance of policies, and conditions the future political process, especially when contending ethical value judgments are involved. On the other hand, public involvement is required if effective policy is to be developed and accepted. METHODS: Using the data from a large-scale national opinion survey, this study evaluates public appraisal of past government efforts to legalize organ transplant from brain-dead bodies in Japan, and examines the public's intent to participate in future policy. RESULTS: A relatively large percentage of people became aware of the issue when government actions were initiated, and many increasingly formed their own opinions on the policy in question. However, a significant number (43.3%) remained unaware of any legislative efforts, and only 26.3% of those who were aware provided positive appraisals of the policymaking process. Furthermore, a majority of respondents (61.8%) indicated unwillingness to participate in future policy discussions of bioethical issues. Multivariate analysis revealed the following factors are associated with positive appraisals of policy development: greater age; earlier opinion formation; and familiarity with donor cards. Factors associated with likelihood of future participation in policy discussion include younger age, earlier attention to the issue, and knowledge of past government efforts. Those unwilling to participate cited as their reasons that experts are more knowledgeable and that the issues are too complex. CONCLUSIONS: Results of an opinion survey in Japan were presented, and a set of factors statistically associated with them were discussed. Further efforts to improve policy making process on bioethical issues are desirable.

Bioethical Issues↗

PubMed2005

Screening for mutations in CYP4V2 gene in Japanese patients with Bietti's crystalline corneoretinal dystrophy.

PURPOSE: To describe the clinical and genetic characteristics of six Japanese families with Bietti's crystalline corneoretinal dystrophy (BCD). DESIGN: Case reports and results of DNA analysis. METHODS: Mutation screening was performed on six unrelated patients with BCD by direct sequencing. The clinical features were characterized by the visual acuity, slit-lamp biomicroscopy, electroretinography, fluorescein angiography, and kinetic visual field testing. RESULTS: An identical IVS6 to 8delTCATACAGGTCATCGCG/insGC mutation in the CYP4V2 gene was identified in five of the patients with BCD; the sixth patient had a novel Trp340X mutation in the CYP4V2 gene. Three patients showed crystalline-like deposits at the limbus by specular microscopy. Ophthalmic findings of all patients had a rapid progression after age 50 years. CONCLUSIONS: Our findings suggest that the IVS6 to 8delTCATACAGGTCATCGCG/insGC mutation is a common mutation in Japanese patients with BCD. Although phenotypic variability was found, the natural course was almost the same in all of our patients.

Adult↗

PubMed2005

Screening for mutations in the IMPDH1 gene in Japanese patients with autosomal dominant retinitis pigmentosa.

PURPOSE: To determine the presence and frequency of mutations in the IMPDH1 gene in Japanese patients with autosomal dominant retinitis pigmentosa (ADRP), and to characterize the clinical characteristics of patients with the Lys238Arg mutation in the IMPDH1 gene. DESIGN: Case reports and results of DNA analysis. METHODS: All 14 coding exons of the IMPDH1 gene were directly sequenced in 96 unrelated patients with ADRP. The clinical features were determined by visual acuity, slit-lamp biomicroscopy, and kinetic visual field tests. RESULTS: Two novel mutations, a Leu227Pro and Lys238Arg, in the IMPDH1 gene were identified in two unrelated families with ADRP. The clinical features associated with the Lys238Arg mutation were an early-onset and severe retinal degeneration. CONCLUSIONS: The most commonly reported Asp226Asn mutation was not found in the Japanese population, instead two novel mutations were found. These findings suggest that mutations of the IMPDH1 gene cause ADRP in the Japanese population.

Adult↗