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Biomedical subjects

K Komori

Publications and source records attributed to K Komori.

At least 37 records · Page 2Linked to original sources
PubMed2001

Increased prevalence of vascular dementia in Japan: a community-based epidemiological study.

BACKGROUND AND OBJECTIVE: It has been suggested that there is a major difference in the ratio of AD to vascular dementia (VaD) between Japan and Western countries. To determine the type-specific prevalence of dementia in community-dwelling elderly from the Japanese community of Nakayama, all patients with dementing illness underwent a CT scan. METHODS: A door-to-door three-phase population survey was carried out on all persons aged 65 years and older residing at home on the prevalence day (January 1, 1997). The ascertainment of cases was made between January 1997 and March 1998. The study included a psychiatric interview; physical, neurologic, and neuropsychologic examinations; comprehensive laboratory tests; and cranial CT. A public health nurse also interviewed a person close to each subject. Dementia was defined according to the Diagnostic and Statistical Manual of Mental Disorders, third edition-revised, criteria, AD according to the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association, and VaD according to Diagnostic and Statistical Manual of Mental Disorders, fourth edition, combined with information from the patient's neurologic history and CT scanning. RESULTS: Of 1438 inhabitants, 1162 (81.0%) completed the protocol. The prevalence of dementia was 4.8%. Of the 60 subjects with dementia, 35% had AD, 47% had VaD, and 17% had dementia resulting from other causes. CONCLUSIONS: The prevalence of dementia was similar to previous reports, but, contrary to results of virtually all studies conducted in developed countries and those recently conducted in Japan, almost half of the cases in the present study appeared to have VaD with neuroradiologic confirmation.

Aged↗
PubMed2001

Alteration of rCBF in Alzheimer's disease patients with delusions of theft.

We investigated the neural substrate of the delusion of theft in patients with Alzheimer's disease (AD). Nine AD patients with only one type of delusion (delusions of theft) and nine age, cognitive function-matched AD patients without any type of delusions were selected from 334 consecutive outpatients of Ehime University Hospital. All subjects underwent (99m)Tc-HMPAO SPECT scanning, and SPECT images were analyzed by Statistical Parametric Mapping (SPM). AD patients with delusions of theft showed significant hypoperfusion in the right medial posterior parietal region compared to patients without delusions. Our data suggest that attention impairment or lack of awareness of illness caused by right parietal dysfunction might play a role in producing the delusion of theft.

Age Factors↗
PubMed2001

Dissection of the regional roles of the archaeal Holliday junction resolvase Hjc by structural and mutational analyses.

Hjc is an archaeal DNA endonuclease, which resolves the Holliday junction in the presence of divalent metals. Combined with mutational analyses, the x-ray structure of the Pyrococcus furiosus Hjc crystal grown in the presence of ammonium sulfate revealed a positively charged interface, rich in conserved basic residues, and the catalytic center (Nishino, T., Komori, K., Tsuchiya, D., Ishino, Y., and Morikawa, K. (2001) Structure 9, 197-T204). This structural study also suggested that the N-terminal segment and some loops of Hjc play crucial roles in the cleavage of DNA. However, a structural view of the interaction between these regions and DNA remains elusive. To clarify the regional roles of Hjc in the recognition of the Holliday junction, further structural and biochemical analyses were carried out. A new crystal form of Hjc was obtained from a polyethylene glycol solution in the absence of ammonium sulfate, and its structure has been determined at 2.16-A resolution. A comparison of the two crystal structures has revealed that the N-terminal segment undergoes a serious conformational change. The site-directed mutagenesis of the sulfate-binding site within the segment caused a dramatic decrease in the junction binding, but the mutant was still capable of cleaving DNA with a 20-fold lower efficiency. The kinetic analysis of Hjc-Holliday junction interaction indicated that mutations in the N-terminal segment greatly increased the dissociation rate constants of the Hjc-Holliday junction complex, explaining the decreased stability of the complex. This segment is also responsible for the disruption of base pairs near the junction center, through specific interactions with them. Taken together, these results imply that, in addition to the secondary effects of two basic loops, the flexible N-terminal segment plays predominant roles in the recognition of DNA conformation near the crossover and in correct positioning of the cleavage site to the catalytic center of the Hjc resolvase.

Amino Acid Sequence↗
PubMed2001

Replication protein A in Pyrococcus furiosus is involved in homologous DNA recombination.

Single-stranded DNA-binding protein in Bacteria and replication protein A (RPA) in Eukarya play crucial roles in DNA replication, repair, and recombination processes. We identified an RPA complex from the hyperthermophilic archaeon, Pyrococcus furiosus. Unlike the single-peptide RPAs from the methanogenic archaea, Methanococcus jannaschii and Methanothermobacter thermoautotrophicus, P. furiosus RPA (PfuRPA) exists as a stable hetero-oligomeric complex consisting of three subunits, RPA41, RPA14, and RPA32. The amino acid sequence of RPA41 has some similarity to those of the eukaryotic RPA70 subunit and the M. jannaschii RPA. On the other hand, RPA14 and RPA32 do not share homology with any known open reading frames from Bacteria and Eukarya. However, six of eight archaea, whose total genome sequences have been published, have the open reading frame homologous to RPA32. The PfuRPA complex, but not each subunit alone, specifically bound to a single-stranded DNA and clearly enhanced the efficiency of an in vitro strand-exchange reaction by the P. furiosus RadA protein. Moreover, immunoprecipitation analyses showed that PfuRPA interacts with the recombination proteins, RadA and Hjc, as well as replication proteins, DNA polymerases, primase, proliferating cell nuclear antigen, and replication factor C in P. furiosus cells. These results indicate that PfuRPA plays important roles in the homologous DNA recombination in P. furiosus.

Amino Acid Sequence↗
PubMed2001

Failure in the detection of aberrant mRNA from the heterozygotic splice site mutant allele for protein S in a patient with protein S deficiency.

A 29-year-old male patient with acute arterial obstruction and a medical history including thrombosis in the deep veins and pulmonary infarction presented with a reduced level of both protein S (PS) activity and free PS. Sequencing of the genomic PS gene in this patient revealed that the patient was heterozygous for the mutant PS allele, in which a nucleotide substitution occurred at the donor splice site in intron 12 (GT to GA). The patient was heterozygous for PS genes having dimorphic codons for Pro626 (CCA/CCG) and the aberrant allele in this patient was associated with the CCA form. Allelic exclusion of PS expression was demonstrated by use of Pro626 (CCA/CCG) dimorphism and only a normal mRNA sequence derived from the CCG-allele was identified in the patient. These findings suggested that the mutation at the splice site in the PS gene caused either defective production of mRNA or the gene may have produced extremely unstable RNA products, leading to reduced levels of PS activity and free PS in this patient.

Adult↗
PubMed2001

Archaeal primase: bridging the gap between RNA and DNA polymerases.

In the evolution of life, DNA replication is a fundamental process, by which species transfer their genetic information to their offspring. DNA polymerases, including bacterial and eukaryotic replicases, are incapable of de novo DNA synthesis. DNA primases are required for this function, which is sine qua non to DNA replication. In Escherichia coli, the DNA primase (DnaG) exists as a monomer and synthesizes a short RNA primer. In Eukarya, however, the primase activity resides within the DNA polymerase alpha-primase complex (Pol alpha-pri) on the p48 subunit, which synthesizes the short RNA segment of a hybrid RNA-DNA primer. To date, very little information is available regarding the priming of DNA replication in organisms in Archaea. Available sequenced genomes indicate that the archaeal DNA primase is a homolog of the eukaryotic p48 subunit. Here, we report investigations of a p48-like DNA primase from Pyrococcus furiosus, a hyperthermophilic euryarchaeote. P. furiosus p48-like protein (Pfup41), unlike hitherto-reported primases, does not catalyze by itself the synthesis of short RNA primers but preferentially utilizes deoxynucleotides to synthesize DNA fragments up to several kilobases in length. Pfup41 is the first DNA polymerase that does not require primers for the synthesis of long DNA strands.

DNA↗
PubMed2001

Crystal structure of the archaeal holliday junction resolvase Hjc and implications for DNA recognition.

BACKGROUND: Homologous recombination is a crucial mechanism in determining genetic diversity and repairing damaged chromosomes. Holliday junction is the universal DNA intermediate whose interaction with proteins is one of the major events in the recombinational process. Hjc is an archaeal endonuclease, which specifically resolves the junction DNA to produce two separate recombinant DNA duplexes. The atomic structure of Hjc should clarify the mechanisms of the specific recognition with Holliday junction and the catalytic reaction. RESULTS: The crystal structure of Hjc from the hyperthermophilic archaeon Pyrococcus furiosus has been determined at 2.0 A resolution. The active Hjc molecule forms a homodimer, where an extensive hydrophobic interface tightly assembles two subunits of a single compact domain. The folding of the Hjc subunit is clearly different from any other Holliday junction resolvases thus far known. Instead, it resembles those of type II restriction endonucleases, including the configurations of the active site residues, which constitute the canonical catalytic motifs. The dimeric Hjc molecule displays an extensive basic surface on one side, which contains many conserved amino acids, including those in the active site. CONCLUSIONS: The architectural similarity of Hjc to restriction endonucleases allowed us to construct a putative model of the complex with Holliday junction. This model accounts for how Hjc recognizes and resolves the junction DNA in a specific manner. Mutational and biochemical analyses highlight the importance of some loops and the amino terminal region in interaction with DNA.

Amino Acid Sequence↗
PubMed2001

Immunohistochemical phenotypic alterations of rabbit autologous vein grafts implanted under arterial circulation with or without poor distal runoff-implications of vein graft remodeling.

Although intimal hyperplasia is a major cause limiting the long-term patency of the vein grafts, its precise mechanisms, including the effect of poor runoff, has not yet been well characterized. We thus designed the present study to try to determine the effect of poor runoff arterial flow to the phenotypic alterations of the graft wall by immnohistochemistry using anti-intermediate filaments (alpha-SM actin, desmin, and vimentin) and anti-myosin heavy chain (SM1, SM2, and SMemb) specific antibodies. Vein grafts implanted under the poor runoff hind limb of rabbits showed enhanced intimal hyperplasia, however, no apparent difference in the cytoskeleton expression, including intermediate filaments and MHC, between two groups until 4 weeks. Interestingly, six of eight vein grafts at 2 weeks after implantation in both groups showed the accumulations of perivascular fibroblast-like phenotype (negative for SM1, alpha-SM actin, and desmin) in some parts of the outer neointima, whereas the inner neointima at 2 weeks and the whole neointima at 4 weeks were mainly occupied by a smooth muscle phenotype (positive for these three). Although the cellular origin of these cells is still unknown, these results suggest that the migration of non-muscle mesenchymal cells is involved in the neointima and thus may provide a clue for better understanding vein graft remodeling.

Anastomosis, Surgical↗
PubMed2001

Successful hyperbaric oxygen treatment of life-threatening hemorrhagic cystitis after allogeneic bone marrow transplantation.

Hemorrhagic cystitis (HC) is a major cause of morbidity after allogeneic bone marrow transplantation (BMT). Many therapies have been investigated to prevent or treat HC, but effective treatment for HC is still limited. While the efficacy of hyperbaric oxygen therapy has been established for HC due to chemotherapy and/or radiation therapy, its role in HC occurring after allogeneic BMT has yet to be defined. We report two cases of life-threatening late-onset HC after allogeneic BMT in children, which resolved after treatment with hyperbaric oxygen.

Bone Marrow Transplantation↗
PubMed2001

Successful and optimized in vivo gene transfer to rabbit carotid artery mediated by electronic pulse.

Several gene transfer methods, including viral or nonviral vehicles have been developed, however, efficacy, safety or handling continue to present problems. We developed a nonviral and plasmid-based method for arterial gene transfer by in vivo electronic pulse, using a newly designed T-shaped electrode. Using rabbit carotid arteries, we first optimized gene transfer efficiency, and firefly luciferase gene transfer via electronic pulse under 20 voltage (the pulse length: P(on)time 20 ms, the pulse interval: P(off) time 80 ms, number of pulse: 10 times) showed the highest gene expression. Exogenous gene expression was detectable for at least up to 14 days. Electroporation-mediated gene transfer of E. coli lacZ with nuclear localizing signal revealed successful gene transfer to luminal endothelial cells and to medial cells. Histological damage was recognized as the voltage was increased but neointima formation 4 weeks after gene transfer was not induced. In vivo electroporation-mediated arterial gene transfer is readily facilitated, is safe and may prove to be an alternative form of gene transfer to the vasculature.

Animals↗
PubMed2001

Non-penetrating vascular clips anastomosis inhibited intimal thickening under poor runoff conditions in canine autogenous vein grafts.

OBJECTIVE: Late graft failure is still a significant problem, particularly in cases with poor runoff vessels. The main cause of late graft failure is intimal thickening of the anastomotic region. Vascular closure system (VCS) clips may provide ideal anastomosis, since they do not penetrate the wall. Therefore, we examined whether the VCS clips affect intimal thickening under poor runoff conditions in the canine autogenous vein grafts. METHODS: A canine poor runoff model was prepared at both femoral veins. Four weeks after the first surgical procedure, two groups were established according to the two different methods of anastomosis employed. The right femoral vein graft was performed using polypropylene sutures, conventional surgical anastomosis (control group), while the left femoral vein graft was performed using VCS clips anastomosis (VCS group). Four weeks after grafting, the vein grafts were removed and the intimal thickening of proximal, distal anastomosis and midportion of the vein grafts were examined histologically. RESULTS: In the control group, flow rate and variation were 26+/-8 ml/min and 51+/-10 dynes/cm(2), respectively. In the VCS group, the flow rate and variation were 23+/-11 ml/min and 44+/-14 dynes/cm(2), respectively. There were no significant differences between the two groups. The average value of intimal thickening of both the anastomotic region and the midportion of the vein graft in the VCS group was significantly inhibited compared to that of the control group. The number of positive cells of masson trichrome stain in the VCS group was significantly less than that of the control group. CONCLUSIONS: These experiments indicate that VCS clips significantly inhibit intimal thickening under poor runoff conditions in canine autogenous vein grafts to a greater extent compared to suture-constructed anastomosis. One mechanism that may account for the decreased intimal thickening is the inhibition of the expression of transforming growth factor-beta (TGF-beta), because the number of positive cells of masson trichrome stain in the VCS group was significantly less than that of the control group.

Animals↗
PubMed2001

Interrater reliability of the Physical Self-Maintenance Scale and the Instrumental Activities of Daily Living Scale in a variety of health professional representatives.

This study was performed to assess interrater reliability of the Japanese version of the Physical Self-Maintenance Scale (PSMS) and the Instrumental Activities of Daily Living Scale (IADL), which are simple and efficient assessment instruments of functional abilities in elderly patients. The subjects were 25 consecutive patients with Alzheimer's disease who were outpatients of the Department of Neuropsychiatry in Ehime University School of Medicine and their principal caregivers. One neuropsychiatrist administered the PSMS and IADL, and all sessions were videotaped. Then one clinical psychologist, one public health nurse and one neurologist, and one occupational therapist from another institution, viewed the videotape and performed reassessments. All interrater reliabilities between the neuropsychiatrist and the neurologist, the public health nurse, the clinical psychologist and the occupational therapist were extremely good. Interrater reliability between the public health nurse and the clinical psychologist, between the clinical psychologist and the neurologist and between the public health nurse and the neurologist was also extremely good. The PSMS and IADL showed good interrater reliability between personnel from different disciplines. They are likely to be useful tests for everyday medical consultations and for field research.

Activities of Daily Living↗
PubMed2001

Inhibitory effect of prostaglandin E 1 on intimal thickening caused by poor runoff conditions in the canine autologous vein grafts.

The efficacy of ONO-1608, a newly developed liposomal formulation of prostaglandin E 1 prodrug, was evaluated on intimal hyperplasia of experimental canine autologous vein grafts under distal poor runoff conditions. The femoral vein was implanted into the femoral artery, preparing a distal poor runoff canine model. After 4 weeks of preparing the poor runoff model, the femoral vein was implanted into the femoral artery. They were then divided into two groups consisting of the control group and the ONO-1608 group. At 4 weeks, the grafts were harvested and intimal hyperplasia of the graft was measured with an ocular cytometer. Intimal cell proliferation was determined by bromodeoxyuridine incorporation 2 weeks after surgery. In addition, the effect of ONO-1608 on the proliferation of platelet-derived growth factor (PDGF)-stimulated human aortic smooth muscle cells (HASMCs) in culture was also investigated. At 4 weeks, the degree of intimal hyperplasia of the graft in the ONO-1608 group was significantly less than that of the control group. The bromodeoxyuridine labeling index 2 weeks after grafting was significantly lower in the ONO-1608 group compared with that in the control group. In addition, ONO-1608 significantly inhibited the proliferation of PDGF-stimulated HASMCs in culture. These results demonstrate the efficacy of ONO-1608 in reducing the degree of intimal hyperplasia of canine autogenous vein grafts under poor runoff conditions. The mechanism of reducing the intimal hyperplasia may be that ONO-1608 inhibited PDGF-stimulated proliferation of the smooth muscle cell. These results suggest that the administration of ONO-1608 may be beneficial in patients who have undergone gone arterial reconstruction.

Alprostadil↗
PubMed2001

Natural course of the functional and morphological changes in canine autogenous arterial graft.

BACKGROUND: We examined the time course of endothelium-dependent and -independent responses in reversed autogenous arterial grafts during regeneration and tissue repair processes after arterial grafting in dogs. MATERIALS AND METHODS: Autogenous arterial grafts implanted in the canine femoral artery were removed, cut into rings and suspended in organ chambers for isometric tension recording on the 1st, 3rd, 7th, 14th and 28th days after implantation. Electron-microscopic examination on the 1st, 3rd,7th, 14th and 28th days after transplantation was also performed. Control arteries were taken from nonsurgically treated femoral arteries. RESULTS: Acetylcholine (ACh) and A23187 caused endothelium-dependent relaxations in arterial grafts throughout the study. Although endothelium-dependent relaxations to ACh and A23187 on the 3rd day after transplantation were only significantly impaired compared to those of control, they were similar to the control within 1 week after grafting. Smooth muscle relaxations in response to sodium nitroprusside in arterial grafts throughout the study were comparable with those of control arteries. No apparent intimal thickening of the arterial grafts was observed. Electron microscopy scanning revealed mild endothelial cell damage in implanted autogenous arterial grafts on the 1st or 3rd day after grafting. Seven to 14 days after grafting, the endothelial cell layer appeared to be normal. CONCLUSIONS: It was observed that the endothelial function remained intact and there was an absence of intimal thickening in the arterial grafts. These observations may explain the improved patency of autogenous arterial grafts compared to the vein grafts in aortocoronary revascularization.

Animals↗
PubMed2001

Comparison between estrogenicities estimated from DNA recombinant yeast assay and from chemical analyses of endocrine disruptors during sewage treatment.

This study discusses the estrogenicity and the extent of estrogenic effects, of sewage and treated sewage in public sewage treatment plants in Japan. The estrogenicity in this study was measured with a DNA recombinant yeast strain. Using this method, 43 chemicals that are suspected to have estrogen-like effects were measured and their estrogenicities were evaluated in terms of 17 beta-estradiol equivalents by comparison with the estrogenicity of 17 beta-estradiol. 17 beta-estradiol equivalents of influent and effluent sampled from 20 sewage treatment plants (STPs) were measured with this method. Because the concentrations of endocrine disruptors (EDs) in the STPs were monitored by the Ministry of Construction (MOC), the estrogenic effects estimated from the chemical data were obtained as a theoretical estrogenicity in terms of 17 beta-estradiol equivalent. The results suggest that STPs effectively reduce the estrogenicity and the theoretical estrogenicity during treatment, and that there were some differences between the estrogenicity assayed by the yeast and the theoretical estrogenicity in many STPs, particularly in influent sewage. Therefore, it is implied that unknown estrogen-like substances or antagonists might exist in influent sewage and treated sewage in STPs.

Biological Assay↗
PubMed2001

[A case of Marchiafava-Bignami disease caused by anorexia nervosa].

A 29-year-old female without alcoholism whose height and weight were 152 cm and 28 kg had complained of severe anorexia since about 10 years ago. The splenium of the corpus callosum showed symmetrically low-intensity area in T1 WI and high-intensity area in T2 WI on her brain MRI. These findings could be reversible by the recovery of her nutritional condition. The findings of neurological and neuropsychological examinations were normal. To our knowledge, this is the first case report of Marchiafava-Bignami disease caused by Anorexia Nervosa.

Adult↗
PubMed2001

[A case of corticobasal degeneration of which movemental disturbances were improved by administration of amantadine].

Corticobasal degeneration(CBD) is a neurodegenerative disorder characterised clinically by apraxia, cortical sensory loss, alien limb, dementia, oculomotor abnormalities, dysarthria, postural instability, akinesia, rigidity, and pyramidal signs. Brain imaging may demonstrate greater abnormalities contralateral to the more affected side. We reported a case of corticobasal degeneration of which praxic impairments were improved by administration of amantadine. The patient was a 63-year-old right-handed woman. She showed marked dysfunction including rigidity, limb kinetic apraxia, cortical sensory loss, ideomotor apraxia, and dressing apraxia. A brain MRI scan revealed bilateral cortical atrophy centered in the postcentral gyrus, more pronounced in the left hemisphere than the right. A SPECT scan showed a decrease in blood flow in the temporo-parieto-occipital regions, more pronounced in the left hemisphere than the right. An EEG showed a diffuse slowness. L-dopa had no effect on the symptoms of rigidity, limb kinetic apraxia, cortical sensory loss, ideomotor apraxia, and dressing apraxia. By administration of amantadine, rigidity and cortical sensory loss did not improve, but some praxic impairments, such as dressing apraxia and ideomotor apraxia, and the EEG improved. Upon withdrawal of amantadine, the improved symptoms deteriorated. Amitriptyline did not improve the deteriorated symptoms. After amantadine was re-administered, the same praxic impairments and the EEG improved again. This suggested that administration of amantadine had some effect on certain praxic impairments and the EEG.

Amantadine↗