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Biomedical subjects

C Tanaka

Publications and source records attributed to C Tanaka.

At least 55 records · Page 3Linked to original sources
PubMed2000

Lack of an association of estrogen receptor alpha gene polymorphisms and transcriptional activity with Alzheimer disease.

BACKGROUND: Long-term cognitive decline in postmenopausal women is associated with aging and Alzheimer disease (AD). Estrogen replacement therapy has been reported to reduce the risk of developing AD. The distribution of estrogen receptors (ERs) in neurons overlaps that of the brain neurons known to develop AD. Estrogen increases the secretion and metabolism of amyloid precursor protein, may help synapse formation, and is reported to protect neurons from toxins. Restriction fragment length polymorphisms (RFLPs) of the ERalpha gene at intron 1 and exon 2 were associated with a low bone mineral density in postmenopausal women and also with AD in a Japanese population. OBJECTIVE: To determine whether ERalpha gene polymorphisms are associated with transcriptional activity and AD. METHODS: A luciferase reporter assay analyzed enhancer activity of the ERalpha gene at intron 1 and exon 2. This activity was evaluated according to the RFLPs. The RFLPs of the ERalpha gene were determined in Japanese patients clinically diagnosed as having AD, white patients diagnosed as having AD at autopsy, and corresponding healthy control subjects. The RFLPs were also evaluated for the contribution of the ERalpha gene RFLPs to AD. RESULTS: We found weak (about 2-fold) enhancer activity of the ERalpha gene, which differed among RFLPs. Although there were racial differences in these polymorphisms, we could not confirm the previously reported association between ERalpha gene polymorphisms and AD. CONCLUSION: Regulatory element of the ERalpha gene was found in intron 1, but we found no association between ERalpha gene polymorphisms and AD.

Aged↗
PubMed2000

Oral ciprofloxacin vs. intravenous ceftriaxone administered in an outpatient setting for fever and neutropenia in low-risk pediatric oncology patients: randomized prospective trial.

BACKGROUND: Infections are one of the major complications in children undergoing chemotherapy. Monotherapy with either ciprofloxacin or ceftriaxone is safe and efficient in low-risk patients (solid tumors and stage I/II lymphomas). The same drugs may be used in an outpatient setting, decreasing costs and the risk of nosocomial infections. PROCEDURE: Low-risk patients (N = 70) with episodes of fever and neutropenia (N = 116) were randomized to receive either oral ciprofloxacin or intravenous ceftriaxone as outpatients. Only one patient had a central venous catheter. RESULTS: Episodes of fever and neutropenia were classified as fever of unknown origin (41% vs. 32%) or clinically documented infection (56% vs. 63%) in the ciprofloxacin and ceftriaxone groups, respectively. Most of these infections were of upper respiratory tract, skin, or gastrointestinal origin. The mean duration of neutropenia was 5 vs. 6 days. Fever persisted for 1-9 days (mean 2 vs. 3 days). Therapy was successful with no modifications in 83% vs. 75% of the episodes. Patients were admitted in 7% vs. 4% of the episodes. No bone or joint side effects were seen in either group. All patients survived. CONCLUSIONS: Outpatient therapy with either oral ciprofloxacin or intravenous ceftriaxone for fever and neutropenia is effective and safe in pediatric patients with solid tumors and stage I/II non-Hodgkin lymphoma (low-risk patients).

Administration, Oral↗
PubMed2000

Amphipathic structure of theonellapeptolide-Id, a hydrophobic tridecapeptide lactone from the Okinawa marine sponge Theonella swinhoei.

Theonellapeptolide-Id (TNLP), a cyclic tridecapeptide lactone, was crystallized from dimethylformamide-water solution. In the asymmetric unit, two peptide molecules were combined with solvent molecules, and the total molecular weight was over 3000 Dalton. The crystal structure including solvent molecules was finally determined at 0.80 A resolution using synchrotron radiation. The conformations of two independent molecules were similar to each other and were also similar to the previously reported structure (Doi, Ishida, Kobayashi, Deschamps and Flippen-Anderson, 1999, Acta Crystallogr Sect C, 55, 796-798). About 13 hydrated water molecules were found at disordered 19 sites; they were located at a certain region to avoid contact with aliphatic side-chains of peptolide in the crystal. The spatial disposition of the solvent molecules and peptides subsequently caused the formation of the amphipathic layer.

Animals↗
PubMed2000

Analysis of accumulated T cell clonotypes in patients with systemic lupus erythematosus.

OBJECTIVE: To compare the accumulated T cell clonotypes in peripheral blood (PB) samples obtained at various times, and the accumulated T cell clonotypes in a PB sample and in an affected kidney, from patients with systemic lupus erythematosus (SLE). METHODS: Peripheral blood mononuclear cells (PBMC) were obtained at 2-4 different times from each of 5 SLE patients, with or without flare-up of the disease; in addition, a biopsied kidney tissue sample was obtained from 1 of the patients. RNA was extracted from each sample and complementary DNA was prepared. Genes that encode the variable region of T cell receptor (TCR) B chains (BV) of 3 BV families, 5S1, 8, and 14, were amplified by reverse transcription-polymerase chain reaction (PCR), and the PCR products were cloned for sequencing. RESULTS: A total of 877 cloned TCR genes was detected in the PBMC samples and the kidney sample. Oligoclonal T cell expansion was detected in 34 of the 36 PCR-amplified BV samples from PBMC (amplification of 3 BV families in 2-4 samples from 5 patients). The composition of clonally expanded T cell clonotypes was relatively stable in the patients with inactive SLE. In contrast, the composition of clonotypes in the PB changed drastically after the patient experienced the active phase of the disease. T cell clonotypes that had accumulated in the kidney appeared to be restricted and distinct from those that had accumulated in the PB of the same patient. CONCLUSION: Different T cell clonotypes expand at different times and at different sites in patients with active SLE. The sensitizing antigens may change over the course of the disease and may be different at each site.

Adult↗
PubMed2000

Joint excursion, handle velocity, and applied force: a biomechanical analysis of ergonometric rowing.

Rowers may sacrifice on-water technique during ergonometric training in an attempt to increase stroke output. This cross-sectional study aimed to identify characteristics of ergonometric rowing technique that could be potentially detrimental to an effective and safe on-water performance. Joint excursion, handle velocity, and applied force were measured in 44 athletes while they performed a 2500 meter race on an instrumented ergometer. Results on four subjects are presented here. Their performance is compared to that of a Barcelona Olympic and World champion rower with 12 years of experience to illustrate how athletes deviate from standard on-water technique. Kinematic data showed knee joint oscillations and out-of-phase hip and knee joint reversals. Horizontal handle velocity curves indicated that higher stroke rates were achieved by a decrease in recovery time. Vertical handle velocity curves exhibited bi-directional variations. The largest amplitude occurred at the end of the drive phase during an upward displacement of the handle that was associated with a jerk in the applied force. Force-time curves at different stroke rates showed greater variability in the initial portion of the drive phase. Perpetuation of these technique deviations may be detrimental to on-water performance. Biomechanical analyses may allow coaches to better monitor technique during ergonometric training.

Adult↗
PubMed2000

Comparison of outer membrane protein genes omp and pmp in the whole genome sequences of Chlamydia pneumoniae isolates from Japan and the United States.

Chlamydia pneumoniae is a widespread pathogen of the respiratory tract that is also associated with atherosclerosis. The whole genome sequence was determined for a Japanese isolate, C. pneumoniae strain J138. The sequence predicted a variety of genes encoding outer membrane proteins (OMPs) including ompA and porB, another 10 predicted omp genes, and 27 pmp genes. All were detected in the whole genome sequence of strain CWL029, a strain isolated and sequenced in the United States. A comparative study of the OMPs of the two strains revealed a nucleotide sequence identity of 89.6%-100% (deduced amino acid sequence identity, 71.1%-100%). The overall genomic organization and location of genes are identical in both strains. Thus, a few unique sequences of the OMPs may be essential for specific attributes that define the differential biology of two C. pneumoniae strains.

Bacterial Outer Membrane Proteins↗
PubMed2000

Novel presenilin-1 mutation with widespread cortical amyloid deposition but limited cerebral amyloid angiopathy.

OBJECTIVE: To clarify the phenotypic heterogeneity in deposition of amyloid beta (Abeta) in the parenchyma and in cerebral vessels of the brains of the patients having presenilin-1 (PS1) mutations. Mutations in PS1 induce increased production of Abeta42(43), resulting in an enhanced overall deposition of Abeta protein within the cerebral cortex. METHODS: Sequence analysis of the PS1 gene of DNA from patients with early onset Alzheimer's disease, and immunostaining of brain tissues by end specific monoclonal antibodies against Abeta. RESULTS: Sequence analysis disclosed a novel mutation (N405S) in the PS1 gene in a Japanese patient with early-onset Alzheimer's disease. Postmortem examination of one patient with N405S showed limited cerebral amyloid angiopathy, whereas postmortem examination of another Japanese patient with Alzheimer's disease with the E184D mutation disclosed severe cerebral amyloid angiopathy. The brains of both patients showed widespread neuritic plaques, neurofibrillary tangles, and neuronal loss. Immunostaining showed that Abeta42 was predominant over Abeta40 in neuritic plaques in both patients, whereas Abeta40 was found to be predominant over Abeta42 in cerebral amyloid angiopathy in the patient with E184D. However, most cortical vessels of the patient with N405S were not reactive with either of the antibodies. CONCLUSION: The N405S mutation of PS1 is a major determinant of cortical Abeta deposition but not cerebral amyloid angiopathy in Alzheimer's disease.

Alzheimer Disease↗
PubMed2000

Induction of a 55-kDa PKN cleavage product by ischemia/reperfusion model in the rat retina.

PURPOSE: To investigate the physiological role of a protein kinase, PKN, and its relation to apoptosis in vivo. METHODS: An ischemia/reperfusion model of the rat retina was created by elevating the intraocular pressure. Retinal samples were obtained after ischemic insult (15-45 minutes) followed by reperfusion (1-7 days). The effect of ischemia on the fragmentation of PKN was examined by immunoblotting and immunocytochemical procedures using the antibody against PKN. N-methyl-D-aspartate (NMDA) or a caspase-3 inhibitor (DEVD-CHO) was administered intravitreally to investigate its effect on the induction of PKN fragmentation. The retinal cell loss in each sample was evaluated by toluidine blue staining. RESULTS: Ischemia induced a 55-kDa PKN cleavage fragment corresponding to the molecular size of the constitutively active fragment of PKN. The appearance of the cleavage fragment depended on the duration of reperfusion and correlated with the occurrence of retinal cell loss. Immunocytochemical analysis revealed that ischemia increased PKN immunoreactivity in the inner layers of the retina. DEVD-CHO significantly inhibited the appearance of the 55-kDa fragment and protected against retinal cell loss. The administration of NMDA also induced cleavage of PKN. CONCLUSIONS: PKN is specifically cleaved by caspase-3 or a related protease during apoptosis in vivo, and PKN cleavage is at least partially initiated by activation of the NMDA receptor.

Animals↗
PubMed2000

A novel mutation at position +12 in the intron following exon 10 of the tau gene in familial frontotemporal dementia (FTD-Kumamoto)

Exonic and intronic mutations in the tau gene cause familial frontotemporal dementia and parkinsonism linked to chromosome 17. Here, we describe a new mutation, consisting of a C-to-T transition at position +12 of the intron following exon 10 of the tau gene in the Kumamoto pedigree, showing frontotemporal dementia. The mutation caused a marked reduction in melting temperature of the tau exon 10-splicing regulatory element RNA and a large increase in exon 10-containing transcripts. Brain tissue from affected individuals showed an abnormal preponderance of exon 10-containing transcripts that was reflected at the protein level by an overproduction of tau isoforms with four microtubule-binding repeats. Immunostaining revealed the presence of tau aggregates in degenerating neurons and glial cells. Isolated tau filaments had a twisted ribbon-like morphology and were made of hyperphosphorylated four-repeat tau isoforms. The additional mutation located dose to the splice-donor site of the intron following exon 10 of the tau gene supports the view that intronic mutations exercize their pathogenic effect by destabilizing RNA secondary structure.

Brain↗
PubMed2000

Dose-dependent pharmacokinetics of cyclosporin A in rats: events in tissues.

Cyclosporin A (CyA) tissue distribution kinetics was extensively studied after single 1.2-, 6-, and 30-mg/kg CyA doses (via 2-min i.v. infusion) to rats. Drug concentrations in blood and various tissues were measured using a specific radioimmunoassay. Based on total blood concentration data alone, CyA systemic pharmacokinetics appeared essentially linear. However, after taking the saturable, nonlinear blood cell binding into account, multiple nonlinear factors were identified. Intrinsic clearance at 30 mg/kg was about half the value at the two lower doses. Tissue distribution was also dose-dependent, with evidence of saturable binding in many tissues. In general, blood binding saturation (dissociation constant K(D) = 0. 18 microg/ml) occurred at a lower dose (concentration) than saturation of tissue binding (K(D), 0.005-0.77 microg/g), such that the volume of distribution at steady state first increased as the dose increased from 1.2 to 6 mg/kg, and then decreased as the dose increased to 30 mg/kg. Tissue binding was further investigated by various graphical analyses. Some organs showed a monophasic (single site) Scatchard plot of the tissue data at steady state, with high K(D) values. In other organs, biphasic binding characteristics were observed with the K(D) values of the high-affinity site in the same range as the K(D) reported for the binding of CyA with cyclophilin, the putative target. Saturable tissue binding may therefore influence not only the pharmacokinetics but also the efficacy of CyA.

Algorithms↗
PubMed2000

[Study on the progression of visual field defect and clinical factors in normal-tension glaucoma].

PURPOSE: We investigated the relationship between the progression of visual field defect and clinical factors in patients with normal-tension glaucoma (NTG). SUBJECTS AND METHODS: Forty-eight eyes of 48 NTG patients undergoing more than 5-year follow-up were enrolled in this study. Their visual field defects ranged between Aulhorn's classification stage 2 and 4, and mean deviation (MD) more than -10 dB measured by Humphrey Field Analyzer (HFA). End points of this follow-up study were defined as follows: in HFA STATPAC 2 glaucoma change probability analysis, more than 5 points which significantly deteriorated at p < 0.05 were found at 2 consecutive examinations (Criterion 1) or a significant decrease in MD value at p < 0.025 was encountered at one examination or in MD value at p < 0.05 at consecutive examinations (Criterion 2). RESULTS: During the follow-up period, 18 eyes of 48 patients satisfied Criterion 1 and 21 eyes Criterion 2. There were no significant differences in clinical factors between patients with progression and without progression. By multiple logistic regression analysis, minimum flow velocity of central retinal artery (CRA) showed significant relation (odds ratio for a 1 cm/sec rise = 0.2215; 95% confidence interval: 0.0530-0.9253) to progression of visual field defect in Criterion 1, and minimum flow velocity of CRA (odds ratio for a 1 cm/sec rise = 0.2099; 95% confidence interval: 0.0506-0.8712) and cholesterol (odds ratio for a 1 cm/dl rise = 1.0332; 95% confidence interval: 0.4096-2.6064) showed significant relation in Criterion 2. CONCLUSION: These results suggests that vascular risk factors of ocular blood flow may play a role in the progression of visual field defects in NTG patients.

Adult↗
PubMed2000

[Factors leading to home care of patients in the terminal stage of malignant diseases--a study of 10 cases].

In order to clarify the factors that lead patients in the terminal stage of malignant diseases to home care, we interviewed ten families of such patients. Among factors involving patients, a strong desire to stay at home and to spend time at home with the family were initially required. Adequate understanding of the patients and their diseases was also needed by families. Other factors include guaranteed medical services in emergencies and/or 24 hours/day 7 days/week care. Patients requested referrals to family physicians, visiting nurses or community health services to cover outpatient clinic functions. It is concluded that a strong desire to stay at home, adequate understanding by the family and guaranteed medical services in emergencies were three significant factors leading to home care of patients in the terminal stage of malignant diseases.

Caregivers↗
PubMed2000

[Muscle involvement of Stormorken's syndrome].

We described two patients, a mother and daughter, of Stormorken's syndrome. The syndrome is characterized clinically by autosomal dominant inheritance, congenital miosis, thrombocytopenia, asplenia and muscle weakness. Both patients had bleeding tendency, ichthyosis of arms, and muscle weakness. The daughter additionally had short stature (146 cm), low body weight (32 kg) and muscle cramp. Neurological findings of the patients included migraine-like headache, cognitive dysfunction, limitation of upward and lateral gaze, and amydriasis. Femoral muscle MRI of the daughter demonstrated decreased volume with patchy high intensity areas in the hamstrings. A muscle biopsy from the daughter showed myogenic changes with muscle fiber necrosis and regeneration, variation in fiber size, tubular aggregates in approximately 5% of fibers, and fibrous tissue proliferation. Dystrophin, dystrophin-associated proteins and dysferlin were normally expressed. Although both patients had elevated creatine kinase levels and generalized muscle wasting, muscle weakness was mild with slow progression. A certain membrane defect in the platelet and muscle fiber might be responsible for the pathogenesis of this syndrome.

Adult↗
PubMed1999

Chromosome of the enterohemorrhagic Escherichia coli O157:H7; comparative analysis with K-12 MG1655 revealed the acquisition of a large amount of foreign DNAs.

A complete Xba I and Bln I cleavage map was constructed for the chromosome of an enterohemorrhagic Escherichia coli (EHEC) O157:H7 strain isolated from an outbreak in Sakai City, Japan, in 1996. A comparative chromosome analysis with E. coli K-12 strain MG1655 was made. The EHEC chromosome was approximately 5600 kb in length, 1 Mb larger than that of MG1655. Despite the marked difference in chromosome length, the location and direction of seven rRNA operons of the EHEC strain were similar to those for MG1655. Overall organization of genes common in both strains is also highly conserved. Chromosome expansion was observed throughout the EHEC chromosome, albeit in an uneven manner. A large portion of the chromosome enlargement was observed in the region surrounding the replication terminus, particularly in a segment containing the terA locus. Sample sequencing of 3627 random shotgun clones suggested the presence of approximately 1550 kb strain-specific DNAs on the EHEC chromosome, most of which are likely to be of foreign origin.

Bacterial Toxins↗
PubMed1999

Plasma Nucleosome Levels in Node-Negative Breast Cancer Patients.

BACKGROUND: A nucleosome is a primary repeating unit of organized DNA in chromatin, and cell death may lead to increased levels of circulating nucleosomes inplasma (PNLs) in various circumstances such as inflammation, pulmonary embolism, autoimmune disease and cancer. MATERIALS AND METHODS: We investigated PNLs in 96 patients with stage 0-III breast cancer (node-negative, n =57; node-positive, n=39), and in 111 women without any evidence of disease as healthy controls. PNLs were detected using the Cell Death Detection ELISAplus kit (Boehringer Mannheim, Japan). RESULTS: The PNLs in normal controls were 0.010 +/- 0.012 units (mean +/- SD), while PNLs were significantly higher in both node-negative breast cancer (0.153 +/- 0.242) and node-positive breast cancer patients (0.116 +/- 0.172) (p <0.01). When PNLs were classified as high (>0.10) and low( </=0.10), no correlation was found between high PNLs and clinicopathological factors such as tumor size, menopausal status, estrogen receptor status, histological type and lymphatic or venous spread in node-negative breast cancer. The relapse-free survival of patients with high PNLs tended to be better than those with low PNLs in both node-negative and node-positive breast cancer. CONCLUSION: Increased PNLs were found in breast cancer patients, and PNLs seem promising as a new prognostic factor for both node-negative and node-positive breast cancer.

Journal Article↗
PubMed1999

A mutation in the microtubule-associated protein tau in pallido-nigro-luysian degeneration.

We detected a missense mutation in exon 10 of tau that causes a substitution at codon 279 (N279K) in a Japanese patient with a familial background of parkinsonism and dementia originally described as pallido-nigro-luysian degeneration. This mutation is the same as one seen in a Caucasian family with pallido-ponto-nigral degeneration. The similarities between these two families suggest a common genetic mechanism that may account for the peculiar distribution of neuroglial degeneration with tauopathy.

Amino Acid Sequence↗