Biomedical subjects

Hajime Sato

Publications and source records attributed to Hajime Sato.

At least 37 records · Page 2Linked to original sources

PubMed2005

Mutations in the pre-mRNA splicing gene, PRPF31, in Japanese families with autosomal dominant retinitis pigmentosa.

PURPOSE: To describe the clinical and genetic characteristics of three Japanese families with autosomal dominant retinitis pigmentosa (ADRP) associated with mutations in the PRPF31 gene. DESIGN: Case reports and results of DNA analysis. METHODS: Mutational screening of the PRPF31 gene was performed on 96 unrelated patients with ADRP by direct sequencing. The clinical features were characterized by complete ophthalmologic examinations. RESULTS: Three mutations in the PRPF31 gene, designated as 1142delG, 1155-1159delGGACG/insAGGGATT, and IVS6 to 3 to -45del, were identified in three unrelated Japanese families with ADRP. The 1142delG and 1155-1159delGGACG/insAGGGATT mutations are novel. The phenotype of affected family members was typical of retinitis pigmentosa (RP). Additionally, we identified asymptomatic obligate carriers. CONCLUSIONS: The 1142delG and 1155-1159delGGACG/insAGGGATT mutations in the PRPF31 gene cause RP. The prevalence of mutations in the PRPF31 gene in Japanese patients with ADRP is approximately 3%. However, it is important to note that there are asymptomatic obligate carriers.

Aged↗

PubMed2005

Targeted disruption of FSCN2 gene induces retinopathy in mice.

PURPOSE: To investigate the morphology and function of photoreceptors in mice with mutation of the FSCN2 gene. METHODS: A mouse line was generated carrying the 208delG mutation (point mutation, or p-type) and another with replacement of exon 1 by the cDNA of a green fluorescent protein (GFP knock-in, or g-type). The expression of retinal mRNA was determined by reverse transcription (RT)-polymerase chain reaction (PCR) and in situ hybridization performed on retinal sections. Morphologic analyses of the retinas were performed by light microscopy (LM) and transmission electron microscopy (TEM) and functional analyses by electroretinogram (ERG). RESULTS: mRNA of FSCN2 was not detected in the retinal mRNA extracted from FSCN2p/p and FSCN2g/g mice. Both FSCN2(+/p) and FSCN2(+/g) mice had progressive photoreceptor degeneration with increasing age detected by LM and structural abnormalities of the outer segment (OS) detected by TEM. Both FSCN2(+/p) and FSCN2(+/g) mice had depressed rod and cone ERGs that worsened with increasing age. CONCLUSIONS: These results indicate that haploinsufficiency of the FSCN2 gene may hamper maintenance and/or elongation of the OS disks and result in photoreceptor degeneration, as in human autosomal dominant retinitis pigmentosa.

Animals↗

PubMed2005

Deleted in polyposis 1-like 1 gene (Dp1l1): a novel gene richly expressed in retinal ganglion cells.

PURPOSE: To characterize a novel gene, deleted in polyposis 1-like 1 (Dp1l1), which is expressed in the retina. METHODS: A systematic screening by subtraction hybridization of the cDNAs from mouse retina and mouse brain was performed to obtain novel genes expressed in the retina. In situ hybridization, immunohistochemistry, and intracellular localization analyses were performed to investigate the expression patterns of Dp1l1. The chromosomal location of Dp1l1 was determined by radiation hybrid mapping. Bioinformatics was used for homology analysis. RESULTS: A novel gene, Dp1l1, was expressed abundantly in the retina. It encodes a 201-amino-acid protein, and the encoded protein is designated mouse TB2-like 1. It is highly homologous to the mouse TB2, which is encoded by deleted in polyposis 1 (Dp1). In situ hybridization and immunohistochemical analyses showed that Dp1l1 mRNA and the TB2-like 1 were localized richly in retinal ganglion cells (RGCs). TB2-like 1 was present in the cytoplasm in a punctate pattern. Dp1l1 was mapped to mouse chromosome 10 by radiation hybrid mapping. CONCLUSIONS: TB2-like 1 is a membrane protein that belongs to the YOP1/TB2/DP1/HVA22 family, and it probably plays an important role in intracellular membrane trafficking in RGCs, based on the properties of other homologous proteins.

Amino Acid Sequence↗

PubMed2005

Does preoperative transbronchial biopsy worsen the postsurgical prognosis of lung cancer? A propensity score-adjusted analysis.

STUDY OBJECTIVES: Our aim was to clarify the hypothesis that the postsurgical prognosis of patients with non-small cell lung cancer (NSCLC) proven by preoperative diagnostic transbronchial biopsy (TBLB) was worse than that of the patients with NSCLC determined at the time of surgery. DESIGN: We entered the propensity score as a continuous variable in the Cox proportional hazards model, along with the success/failure of TBLB and other covariates that were adjusted for the bias inherent to the success/failure of the TBLB examination. PATIENTS: Five hundred ninety-nine consecutive patients with NSCLC undergoing complete resection were divided into two groups. Pathologic diagnosis by TBLB was preoperatively determined in patients belonging to group 1 (n = 367). TBLB was unsuccessful and exploratory thoracotomy or thoracoscopy was followed by surgical resection in patients belonging to group 2 (n = 232). The overall recurrence-free survival rate was examined as the surgical outcomes. RESULTS: The postsurgical recurrence-free rate was significantly higher in group 2 than in group 1. Group 2 patients showed better prognosis than group 1 patients, even when the data between the two groups were adjusted by propensity score. When the groups were subdivided by the pathologic stage of disease, the subgroup consisting of group 2 patients with stage IA and IB lung cancer still showed a higher recurrence-free rate than those in group 1 by propensity score analysis. CONCLUSIONS: The postsurgical prognosis of the patients with NSCLC was significantly better if the preoperative TBLB was unsuccessful. This result suggested that advanced NSCLC had a tendency to be diagnosed with TBLB and, possibly, that the TBLB procedure might worsen the prognosis of patients with resectable NSCLC. We suggest that intraoperative diagnosis followed by the consecutive resection of NSCLC may be beneficial for improving the surgical outcomes of NSCLC patients.

Adenocarcinoma↗

PubMed2005

Synthesis of diverse asparagine linked oligosaccharides and synthesis of sialylglycopeptide on solid phase.

Oligosaccharides are linked to the protein surface and play roles in a number of biological events. Therefore, much attention is being paid to research to investigate the function of the oligosaccharides. In order to investigate the function of oligosaccharides, many synthetic approaches have been examined by synthesizing O-linked or N-linked glycopeptides. Synthesis of O-linked type oligosaccharides is relatively feasible compared to that of N-linked oligosaccharides, because the number of sugar components in the former oligosaccharides is small. In the biosynthesis of oligosaccharides, only N-linked oligosaccharide is reconstructed from the high mannose-type to the hybrid and complex types at the Golgi apparatus. This scientific question, namely, why only N-glycan should change its structure, has been paid much attention and convenient synthesis for both N-glycan and glycopeptide having N-glycans has been examined in order to study the role of N-glycan. In this review, we would introduce recent synthetic developments focusing on the synthesis of N-linked glycopeptides and its analogues.

Asparagine↗

PubMed2005

Effects of pesticides on the peripheral and central nervous system in tobacco farmers in Malaysia: studies on peripheral nerve conduction, brain-evoked potentials and computerized posturography.

We examined the effects of pesticides on the central and peripheral nervous system in the setting of a tobacco farm at a developing country. Maximal motor and sensory nerve conduction velocities (MCV and SCV, respectively) in the median, sural and tibial nerves, postural sway, and brain-evoked potentials (auditory event-related and visual-evoked potentials) were measured in 80 male tobacco farmers and age- and sex-matched 40 controls in Kelantan, Malaysia. Median SCV (finger-wrist) in farmers using Delsen (mancozeb, dithiocarbamate fungicide), who showed significant decrease of serum cholinesterase activities, were significantly lower compared with the controls. Sural SCV in farmers using Fastac (alpha-cypermethrin, pyrethroid insecticide) and median MCV (elbow-wrist) in farmers using Tamex (butralin, dinitroaniline herbicide) were significantly slowed compared with their respective controls. In Delsen (mancozeb, dithiocarbamate) users, the power of postural sway of 0-1 Hz was significantly larger than that in the controls both in the anterior-posterior direction with eyes open and in the right-left direction with eyes closed. The former type of sway was also significantly increased in Tamaron (methamidophos, organophosphorus insecticide) users. In conclusion, nerve conduction velocities and postural sway seem to be sensitive indicators of the effects of pesticides on the central and peripheral nervous system.

Adult↗

PubMed2005

[History of Hansen's disease control policy in the United States].

Federal government set up the institutions for the study and treatment of Hansen's disease patients in Hawaii in 1905. Then in 1917, a legislation was made to build a national leprosarium (leper home), authorize the Surgeon General (SG) to receive into that institution any person afflicted with leprosy who presents himself or herself for care, detention, and treatment, or any person afflicted with leprosy duly consigned to said home by the proper health authorities. The National Leprosarium (later renamed as National Hansen's Disease Center) opened in Carville in 1922. Although promin treatment had started in the early 1940s, the Public Health Service Act of 1944 retained the SG's authority for detention and apprehension. Discharge codes were gradually loosened since then, but the efforts to revise the Act were never successful for a long time. It was in 1985 when the Act was abolished. Provision of long-term care for new patients at the Center was terminated finally in 1997.

Communicable Disease Control↗

PubMed2004

Clinical features of a Japanese family with autosomal dominant retinitis pigmentosa associated with a Thr494Met mutation in the HPRP3 gene.

PURPOSE: To determine the clinical features of a Japanese family with autosomal dominant retinitis pigmentosa (ADRP) associated with a Thr494Met mutation in the HPRP3 gene. METHODS: Mutational screening by direct sequencing was performed on 96 unrelated patients with ADRP. The clinical features were determined by visual acuity, slit-lamp biomicroscopy, electroretinography, fluorescein angiography, and kinetic visual field testing. RESULTS: A Thr494Met mutation in the HPRP3 gene was found in one family and it cosegregated with ADRP in the three affected members. The ophthalmic findings were those of typical retinitis pigmentosa with rapid progression after 40-years-of-age. One patient also had retinoblastoma as a child. CONCLUSION: We conclude that the Thr494Met mutation in the HPRP3 gene causes ADRP in Japanese patients. This mutation was found in 1% of patients with ADRP in Japan.

Adult↗

PubMed2004

Novel 2336-2337delCT mutation in RP1 gene in a Japanese family with autosomal dominant retinitis pigmentosa.

PURPOSE: To determine the frequency and kinds of mutations in the RP1 gene, and to characterize the clinical features of a Japanese family with autosomal dominant retinitis pigmentosa (ADRP) with a novel 2336 to 2337delCT mutation in the RP1 gene. DESIGN: Case reports and results of DNA analysis. METHODS: Mutational screening by direct sequencing was performed on 96 unrelated patients with ADRP. The clinical features were determined by complete ophthalmologic examinations. RESULTS: A novel 2336 to 2337delCT mutation in the RP1 gene was identified in two patients from a Japanese family with ADRP. In addition, three families with ADRP carried a previously reported nonpathogenic Arg1933X mutation. The ophthalmic findings with a 2336 to 2337delCT mutation were similar to those of typical retinitis pigmentosa with rapid progression after age 40 years. CONCLUSIONS: The most common Arg677X mutation in the white population was not found in the Japanese population; instead a novel mutation was found.

Aged↗

PubMed2004

Novel 615delC mutation in the CRX gene in a Japanese family with cone-rod dystrophy.

PURPOSE: To characterize the clinical features of a Japanese family with cone-rod dystrophy associated with a novel 615delC mutation in the cone-rod homeobox (CRX) gene. DESIGN: Case reports and results of DNA analysis. METHODS: Mutational screening by direct sequencing was performed for the three exons in the CRX gene. The clinical features were evaluated by visual acuity measurements, electroretinography, and kinetic visual field testing. RESULTS: A 615delC mutation in the CRX gene was identified and found to cosegregate with cone-rod dystrophy. The ophthalmic findings included cone-rod dystrophy with negative-type electroretinograms (ERGs) and a rapid progression after the age of 40 years. CONCLUSION: These findings indicate that the 615delC mutation causes cone-rod dystrophy with a negative-type ERG. The genotype-phenotype correlation in the CRX gene in our patient and others reported in the literature suggest that the negative-type ERG might be a good sign for having a mutation in the CRX gene.

Codon, Nonsense↗

PubMed2004

Neurocognitive outcome after retrograde cerebral perfusion.

BACKGROUND: Neurocognitive outcome in patients undergoing thoracic aortic surgery using retrograde cerebral perfusion (RCP) remains uncertain. METHODS: Forty-two patients undergoing thoracic aortic surgery using RCP were enrolled in the study. The patients' neurocognitive state was assessed by the revised Wechsler Adult Intelligence Scale (WAIS-R) a few days before operation, at 2 to 3 weeks, and at 4 to 6 months after operation. RESULTS: There were no stroke, seizure, and hospital death. Significant performance deterioration was observed in digit span, arithmetic, and picture completion of the WAIS-R subtests. Bivariate comparison showed that older age (late vocabulary, late similarities, and late object assembly), longer RCP time (early picture arrangement, and early block design), later awake time (early and late picture arrangement, and early block design), longer respirator use (early and late digit span, late picture arrangement), longer ICU time (late picture completion, early and late picture arrangement, and early block design), and longer hospital stay (early picture arrangement) were significantly associated with the decline in neurocognitive performance. Stepwise logistic regression analysis disclosed that older age (late similarities and late object assembly), later awake time (late picture arrangement), and longer respirator use (early and late digit span, and late picture arrangement) were most predictive for the decline in neurocognitive performance. CONCLUSIONS: On average, digit span, arithmetic, and picture completion tests were most sensitive in detecting the decline in neurocognitive performance. The relationship between the duration of RCP and neurocognitive test results was not significant.

Aged↗

PubMed2004

Clinical features of Japanese families with a 402delT or a 555-556delAG mutation in choroideremia gene.

PURPOSE: To characterize the clinical features of two Japanese families with choroideremia associated with a 402delT and a 555-556delAG mutation in the choroideremia gene (CHM). METHODS: Four affected members and one obligate carrier from two Japanese families with choroideremia were studied. To detect mutations of the CHM gene, the products of polymerase chain reaction were directly sequenced in both directions. The ophthalmologic examination included best-corrected visual acuity, slit-lamp examination, fundus examination, kinetic perimetry, electroretinography, and fluorescein angiography. RESULTS: A 402delT and a 555-556delAG mutation were found in two Japanese families with choroideremia. All affected members had night-blindness, progressive constriction of the visual field, chorioretinal atrophy, and mottled appearance of the retinal pigment epithelium. The obligate carrier had mild patchy areas of retinal pigment epithelial atrophy with no visual symptoms. CONCLUSION: The authors found a 402delT and a 555-556delAG mutation in the CHM gene, one of which (402delT) is a novel mutation. They conclude that these mutations cause choroideremia in Japanese families.

Adaptor Proteins, Signal Transducing↗

PubMed2004

[Social consensus on medical technology policy: ethical issues and citizen participation].

Social consensus is considered to be a necessary condition for a policy to be introduced and implemented effectively. This is the case with the approval, regulation and prohibition of certain advanced medical research and technology, especially when they could invoke moral disputes in society. Public policies on organ transplantation, definition of death, euthanasia, genetic screening and diagnosis, and human stem cell research are recent examples. The concept of consensus, however, is elusive, along with the measures to secure it. Technocratic decision making, as a paternalistic activity frequently led by experts, sometimes poses a challenge to democratic decision making, supposedly based on a well-informed and rational public. It also remains to be proved whether public involvement in policymaking can be a solution to ethical value conflicts in society. From the perspective of policy sciences, this paper first introduces the concept of consensus, especially consensus on moral issues in pluralistic societies, and its implications to public policy, including citizen participation in decision making. Then, it briefly explains the historical background with which social consensus and public involvement have increasingly flourished in the field of technology assessments and technology policy making, including biomedical technology. Next, major institutions, governmental and nongovernmental, involved in the ethical aspects of medical research and technology, are presented along with their efforts for citizen participation. Finally, the paper discusses some of the future agendas on this issue.

Bioethics↗

PubMed2004

Practical efficacy of telmisartan for decreasing morning home blood pressure and pulse wave velocity in patients with mild-to-moderate hypertension.

The current guideline-recommended blood pressure values are difficult to maintain in general practice, partly due to the lack of ideal anti-hypertensive agents. Since morning hypertension has a high correlation with cardiovascular events, expectations that telmisartan, a long-acting angiotensin-II type-1 receptor blocker (ARB), can improve cardiovascular mortality are high. In this study, the efficiency of telmisartan in reducing morning hypertension and pulse wave velocity (PWV) as a practical surrogate endpoint was investigated. Seventeen unsupervised and 7 untreated hypertensive patients were prescribed telmisartan 40 mg/day for 3 months. Medication already prescribed upon enrollment in this study was continued, with the exception of ARBs (all of which turned out to be losartan 50 mg/day), which were discontinued and replaced with telmisartan. Morning home blood pressure (MHBP), office blood pressure (OBP), and brachial-ankle PWV (baPWV) were investigated in a prospective fashion. A stratified analysis was performed regarding previous use (group L) or non-use (group N) of losartan. Over a 3-month period, telmisartan was found to significantly reduce both OBP (from 153+/-13/85+/-9 to 141+/-17/80+/-7 mmHg (p <0.01)) and MHBP (from 153+/-23/93+/-11 to 137+/-22/82+/-10 mmHg (p <0.001)). Surprisingly, 7 patients (70%) from group L achieved an OBP of less than 140/90 mmHg by simply changing their medication to telmisartan. Furthermore, baPWV fell significantly from 1,892+/-334 cm/s to 1,672+/-324 cm/s (p <0.01), which was greater than the change in baPWV estimated by OBP reduction. Here it must be mentioned that there were no significant differences between group L and group N in the courses of blood pressures and baPWV. In conclusion, telmisartan 40 mg/day was found to be effective for reducing MHBP and arterial wall stiffness in patients with mild-to-moderate hypertension, and thus may also be effective for improving cerebrocardiovascular mortality.

Aged↗

PubMed2004

The limiting factors for the transxiphoid approach in congenital cardiac surgery.

OBJECTIVE: Minimally invasive cardiac surgery is currently being performed for a wide variety of cardiothoracic procedures. Since August 1998, the transxiphoid approach using a direct cannulation to the ascending aorta has been selected for the closure of atrial septal defects (ASD) and ventricular septal defects (VSD) in our institution. However, this approach cannot be performed for all patients because of the small "xiphoid window." We analyzed the factors limiting this approach to determine the best factor predicting risk. METHODS: Of 26 patients who had an ASD or a VSD, 14 underwent complete repair using a transxiphoid approach. Preoperative data collected for all patients included the relationship between the right ventricular outflow tract and the lower sternum (the RVSA) in the cineangiograph. Multiple logistic regression analysis was used to investigate which of the factors best predicted whether the transxiphoid approach should be adopted. RESULTS: The factors best predicting this approach were the combination of RVSA and body surface area (BSA) (odds ratios of 2.982 [P = .018] and 0.925 [P = .046], respectively). With the logistic model used in a prospective study of 6 consecutive patients, we were completely successful in predicting whether the transxiphoid approach could be performed. CONCLUSION: The combination of RVSA and BSA was the limiting factor for using the transxiphoid approach in congenital cardiac surgery.

Cardiac Surgical Procedures↗

PubMed2004

An instrument capable of grading visual function: results from patients with retinitis pigmentosa.

There was no device to grade visual function in patients with retinitis pigmentosa (RP). We have therefore developed an instrument capable of measuring and quantifying the visual capabilities, and here present the results from patients with RP. In total, 118 eyes of 59 patients, 26 men and 33 women, with RP were studied. Seven eyes had hand movement (HM) and eight had light perception (LP) vision, and the others had better visual acuity. The Low Vision Evaluator (LoVE) consists of a pair of goggles with white, light-emitting diodes as the stimulus, a control box, an on-off button to signal the detection of the stimulus, and a printer for permanent records. There are 15 luminance levels of stimuli (combination of 5 intensities and 3 durations). The stimuli are delivered in a random sequence with an audio signal presented 0.3 seconds prior to the light stimulus. Each eye was tested separately, and each stimulus magnitude (intensity x duration) was presented 3 times for a total of 27 stimuli per eye. With 6 catch trials (audio signal without a light stimulus), a total of 60 trials were examined in a full examination. The conventional visual acuity and kinetic visual fields were determined. 59 patients had different visual acuities that ranged from no light perception (NLP) to 1.5 vision, and visual field sizes that ranged from 0.0001 to 3.96 steradians. The visual acuity and visual field size were significantly correlated with the LoVE score (r=0.58 and 0.64, respectively; p<0.01). These results indicate that the LoVE is capable of grading the visual function of RP patients with various visual acuities and visual fields. The testing procedures are simple for the patient and examiner, and this instrument can be used to assess the effectiveness of medical and surgical therapy.

Adult↗

PubMed2004

Alleles responsible for ABO phenotype-genotype discrepancy and alleles in individuals with a weak expression of A or B antigens.

ABO types obtained from evidentiary samples have been used effectively to obtain the initial information leading to the apprehension of culprits in Japanese criminal investigations. A simple ABO genotyping method using multiplex sequence-specific PCR and capillary electrophoresis was developed as a supplement to serological ABO typing. Limitations in predicting a phenotype based on genotype were evaluated using 1134 randomly selected Japanese peripheral blood samples. A concordance rate of 99.82% (1132/1134 samples) was found between genotypes and phenotypes defined as Groups A, B, AB, and O. Sequencing analysis revealed that one discrepant sample contained an O allele having a previously unreported point mutation at the primer binding site in exon 6, and another discrepant sample contained an O allele lacking the guanine deletion at nt 261 (the O301 allele). Therefore, the existence of such alleles must be given some consideration when predicting phenotype based on genotype.

ABO Blood-Group System↗

PubMed2004

Mitochondrial DNA heteroplasmy among hairs from single individuals.

A denaturing gradient gel electrophoresis (DGGE) assay was used to detect mitochondrial DNA (mtDNA) sequence heteroplasmy in 160 hairs from each of three individuals. The HV1 and HV2 heteroplasmic positions were then identified by sequencing. In several hairs, the heteroplasmic position was not evident by sequencing and dHPLC separation of the homoduplex/heteroduplex species was carried out with subsequent reamplification and sequencing to identify the site. The overall detection frequency of sequence heteroplasmy in these hairs was 5.8% (28/480) with DGGE and 4.4% (21/280) with sequencing. Sequence heteroplasmy of hair was observed even when the reference blood sample of the individual was homoplasmic. The heteroplasmic positions were not necessarily observed at sites where high rates of substitution have been reported. In two hairs, a complete single base change from the reference blood sample was observed with sequencing, while the heteroplasmic condition at that site in the hair was observed using DGGE. The DGGE results in such samples would serve as an aid in considering the possibility of match significance. In a forensic case, this situation would lead to the possibility of a failure to exclude rather than to be inconclusive.

Chromatography, High Pressure Liquid↗