[Pelizaeus-Merzbacher disease].
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Female↗
Biomedical subjects
T Fukuda
Publications and source records attributed to T Fukuda.
[Cost and effectiveness of exercise therapy for patients with essential hypertension].
PURPOSE: While exercise therapy is established as an appropriate treatment for essential hypertension, its economic profile has not been fully evaluated. The purpose of this study is to evaluate cost and effectiveness in comparison with drug therapy. SUBJECTS AND METHODS: The study subjects were hypertensive patients under treatment at an outpatient clinic. Fifty-seven were selected on a non-randomized manner for exercise therapy and the same number of patients was chosen for drug therapy after matching age, sex, medication and complications. The following data were collected during three months of intervention. 1) Effectiveness: Change of systolic blood pressure before and after the intervention. 2) Cost: equipment, personnel expenses for exercise therapy and fees for health check-ups (exercise therapy); fees for consultation, laboratory examination and medications (drug therapy), 3) Cost-effectiveness: cost per 1 mmHg systolic blood pressure reduction. We evaluated the variance of cost-effectiveness by controlling the number of program participants, personnel expenses, and equipment expenses of exercise therapy. We also simulated how the cost-effectiveness of exercise therapy would improve by modifying the number of exercise participants, personnel and equipment expenses. RESULTS: The cost-effectiveness per 1 mmHg systolic blood pressure reduction was yen 11,268 for exercise therapy and yen 2,441 for drug therapy. Extending program facilities and increasing the number of participants would improve the cost-effectiveness of exercise therapy, but there were limitations to how far this could be achieved in the hospital setting. CONCLUSION: Differences in cost-effectiveness between exercise and drug therapies are attributed to differences in personnel expenses. Although they could be reduced by managerial effort of the hospital to some extent, outsourcing of exercise therapy to community-based facilities should be considered.
Cost-Benefit Analysis↗
[Japanese guideline for the diagnosis and management of bronchial asthma (1998)--its results and reversion].
Japanese guideline for the diagnosis and management of bronchial asthma was initially reported in 1998 and revised in 2000. This guideline was based on two former guidelines which were made by Japanese Allergology Society in 1993 and NIH.NHLBI in 1995 (GINA). New version of this guideline in 2000 pointed that the efficacy and adverse reaction of leukotriene receptor antagonists, the effectiveness of new inhaled corticosteroid (fluticasone propionate), and transdermal administration of beta-2 stimulant (tulobuterol hydrochloride). The precise evaluation of this guideline in terms of propriety, reliability, applicability and so on was not performed.
Administration, Cutaneous↗
[Temporary placement of inferior vena cava filter prior to transcatheter arterial embolization (TAE) for hepatocellular carcinoma with IVC tumor thrombus--prevention of pulmonary tumor emboli after TAE].
A 66-year-old-man with a right huge hepatocellular carcinoma (HCC) extending into both the right portal vein and the right atrium underwent transcatheter arterial embolization (TAE) via the right hepatic artery. Prior to the TAE, a temporary inferior vena cava (IVC) filter was placed suprarenally for prevention of pulmonary tumor emboli. When we replaced the temporary IVC filter with a new one 7 days after the TAE, the filter which was pulled out of the IVC captured a fragment of the tumor thrombus. A histopathological specimen demonstrated only ghost cells. The patient has been followed at our outpatient clinic without any tumor thrombus or pulmonary infarction for 13 months after this procedure.
Aged↗
Study of the effects of microgravity on cell growth of human antibody producing cells and their secretions.
Several attempts have been made to investigate the effects of microgravity on the growth and function of animal cells. Cellular activation of immune T lymphocytes is greatly affected by microgravity. On the other hand, little is known about the effects of microgravity on B lymphocytes, another major class of immune lymphocytes, their growth or antibody production. Our approach to investigate the human B lymphocytes was to compare cell growth, nutrient consumption, and antibody secretion by a human B cell hybridoma between the cells cultured in space and the ground culture.
Ammonia↗
C-type natriuretic peptide concentrations in the plasma and cerebrospinal fluid of patients with subarachnoid hemorrhage.
BACKGROUND: Cerebral vasospasm is a poor resulting outcome of a ruptured cerebral aneurysm; to clarify the mechanism of vasospasm it is important to improve this outcome. C-type natriuretic peptide (CNP) is present in the brain as a cerebral vasodilator; it is also an endothelium-derived relaxing factor produced via cGMP. We speculated that CNP might be an inhibitor of cerebral vasospasm after subarachnoid hemorrhage (SAH). METHODS: To clarify the role of CNP in cerebral vasospasm after SAH, we conducted 1 week monitoring of CNP concentrations in the plasma and cerebrospinal fluid (CSF) of 26 patients who had undergone clipping within 24 hours of the occurrence of SAH, and divided them into group A (positive for angiographic spasm) and group B (negative for angiographic spasm). We also examined CNP concentrations in the CSF of patients who were receiving spinal anesthesia for small orthopedic operations, as reference patients. RESULTS: The CNP concentration in the CSF on day 1 was higher than in the reference patients and decreased in both test groups, but we did not observe any significant difference between the groups. CNP concentrations in the plasma did not change in either group. CONCLUSIONS: CNP concentrations in the CSF were high in the acute phase after SAH, whereas plasma CNP concentrations remained constant. However, our findings did not support our hypothesis because we did not find any relationship between vasospasm and changes in CNP concentrations in the CSF.
Adult↗
A novel anti-rheumatic drug suppresses tumor necrosis factor-alpha and augments interleukin-10 in adjuvant arthritic rats.
Tumor necrosis factor-alpha (TNF-alpha) plays an important role in the pathology of rheumatoid arthritis. When N-[1-(4-¿[4-(pyrimidin-2-yl)piperazin-1-yl]methyl¿phenyl)cycloprop yl] acetamide (Y-39041) (3-30 mg/kg) was orally administered to rats with established arthritis from day 15 to day 20, hindpaw volume was significantly reduced. This inhibitory activity of Y-39041 was kept up after administration was stopped. On day 17 Y-39041 suppressed lipopolysaccharide-induced TNF-alpha and interleukin-6 production in serum at doses of 3-30 mg/kg, and augmented interleukin-10 production at doses of 10 and 30 mg/kg. The finding that Y-39041 suppresses TNF-alpha and interleukin-6 production and augments interleukin-10 production could be beneficial in the therapy of chronic inflammatory diseases.
Acetamides↗
Analysis of deletion mutations of the rpsL gene in the yeast Saccharomyces cerevisiae detected after long-term flight on the Russian space station Mir.
Using the yeast Saccharomyces cerevisiae on board the Russian space station Mir, we studied the effects of long-term space flight on mutation of the bacterial ribosomal protein L gene (rpsL) cloned in a yeast-Escherichia coli shuttle vector. The mutation frequencies of the cloned rpsL gene on the Mir and the ground (control) yeast samples were estimated by transformation of E. coli with the plasmid DNAs recovered from yeast and by assessment of the conversion of the rpsL wild-type phenotype (Sm(S)) to its mutant phenotype (Sm(R)). After a 40-day space flight, some part of space samples gave mutation frequencies two to three times higher than those of the ground samples. Nucleotide sequence analysis showed no apparent difference in point mutation rates between the space and the ground mutant samples. However, the greater part of the Mir mutant samples were found to have a total or large deletion in the rpsL sequence, suggesting that space radiation containing high-linear energy transfer (LET) might have caused deletion-type mutations.
Base Sequence↗
TH protein and mRNA in nigrostriatal dopaminergic neurons are down-regulated by continuous but not intermittent apomorphine.
Levels of tyrosine hydroxylase (TH) and TH mRNA were measured after administration of dopamine agonists for a long period of time to elucidate the long-term feedback inhibition of dopamine synthesis in nigrostriatal dopaminergic neurons. Continuous infusion, which desensitized presynaptic dopamine receptors, but not repeated administration, down-regulated TH and TH mRNA levels. This suggests levels of TH protein and mRNA are only feedback inhibited by the continuous stimulation of postsynaptic dopamine receptors.
Animals↗
A new Western blotting method using polymer immunocomplexes: detection of Tsc1 and Tsc2 expression in various cultured cell lines.
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Animals↗
[Physiopathological interpretation and progress in diagnosis and treatment. 6. RS3PE syndrome].
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Aged↗
Identification of negative regulatory regions within the first exon and intron of the BCL6 gene.
Chromosomal translocations involving BCL6 gene are frequent in human B-cell lymphomas. Chromosomal breaks preferentially occur within a 3-kb region containing the first exon and intron. Recent reports have revealed that internal deletions or point mutations also are common in this region, suggesting that structural alteration of this region may be a crucial event in the development of lymphomas. In this study, we identified two regions in the BCL6 gene that negatively regulate BCL6 expression. One region, ES, is located within the first exon between nucleotides +472 and +543, and a second region, IS, is located between +783 and + 918 of the first intron. A consensus nucleotide sequence for the binding of the BCL6 protein itself was found within the ES region. An electrophoretic mobility shift assay and a co-transfection experiment using a BCL6 expression vector showed that transcription of the BCL6 gene was negatively regulated by the BCL6 gene product. The IS region which is included in the regions commonly deleted in B-cell lymphomas had a silencer activity. Structural alterations of these two regions may play roles in the deregulated expression of the BCL6 gene in B-cell lymphomas.
Cell Transformation, Neoplastic↗
Taurine attenuates hypertrophy induced by angiotensin II in cultured neonatal rat cardiac myocytes.
The effect of taurine on angiotensin II-induced changes in cell morphology and biochemistry of the cultured neonatal cardiomyocyte was examined. Angiotensin II (1-100 nM) alone caused a slow increase in the surface area of the myocyte accompanied by an induction of the expression of atrial natriuretic peptide (ANP) and an upregulation of transforming growth factor beta(1) gene (TGF-beta(1)). The signaling pathway of angiotensin II (1-100 nM) was found to proceed through protein kinase C and the rapid activation of mitogen-activated protein (MAP) kinases. Pretreatment of the myocyte with taurine (20 mM) in the absence of angiotensin II had no visible effect on cell size or growth rate. However, the cells that were pretreated with taurine (20 mM) for 24 h exhibited reduced responsiveness to angiotensin II (100 nM) relative to surface cell area enlargement and the upregulation of the late and growth factor genes(ANP, TGF-beta(1)). Angiotensin II-mediated activation of the MAP kinases (extracellular signal-regulated protein kinase 1/2: ERK1/2) was not blocked by taurine. Taurine reduced the phosphorylation of a 29-kDa protein, a reaction which was enhanced by angiotensin II and appears to involve protein kinase C step. The results indicate that taurine is an effective inhibitor of certain aspects of angiotensin II action.
Angiotensin II↗
A novel human rad54 homologue, Rad54B, associates with Rad51.
Members of the SNF2/SWI2 family, characterized with sequence motifs similar to those found in DNA and RNA helicases, play roles in various aspects of cellular fundamental processes such as transcriptional regulation, chromosome stability, nucleotide excision repair, and recombination. We have isolated a novel member of the human SNF2/SWI2 family, RAD54B, which is highly homologous to mammalian RAD54. The RAD54 gene is a member of the RAD52 epistasis group which is involved in the recombinational repair of DNA damage. Here we demonstrate that human Rad54B (hRad54B), like human Rad54 (hRad54), associates with human Rad51 (hRad51). Both hRad54B and hRad54 associate with hRad51 through their NH(2)-terminal domains, but there are differences in their ways of association with hRad51. In contrast to Rad54, whose association with Rad51 is induced by ionizing radiation, Rad54B associates with Rad51 constitutively in immunoprecipitation experiments. Also, the failure to detect the interaction between hRad54B and hRad51 in the yeast two-hybrid assay suggests that their interaction, unlike that between hRad54 and hRad51, may be indirect. Immunofluorescence microscopy revealed that hRad54B formed nuclear foci that colocalized with hRad51, hRad54, and BRCA1. These findings suggest that Rad54B may be functionally distinct from Rad54, although it may play an active role in recombination processes in concert with other members of the RAD52 epistasis group.
Adenosine Triphosphatases↗
The decreased in vivo clearance of CYP2D6 substrates by CYP2D6*10 might be caused not only by the low-expression but also by low affinity of CYP2D6.
CYP2D6 exhibits genetic polymorphism with interindividual differences in metabolic activity. We have found a significant influence on the pharmacokinetics of venlafaxine by the CYP2D6*10 allele in a Japanese population. CYP2D6.10, which is translated from CYP2D6*10, has two amino acid substitutions: Pro34 --> Ser and Ser486 --> Thr. In this study, CYP2D6.10 was expressed in Saccharomyces cerevisiae and its catalytic activity for CYP2D6 substrates was investigated. The CYP2D6*10B- and *10C-associated cDNA were isolated from human lymphocyte genotyped as CYP2D6*10. In addition, three forms of CYP2D6, Pro34/Thr486 (PT), Ser34/Ser486 (SS), and Pro34/Ser486 (wild type, CYP2D6.1), were constructed by PCR-site mutagenesis to clarify the effects of the two amino-acid substitutions. The expression of CYP2D6 protein was confirmed by immunoblotting using CYP2D antibody. The absorbance at 450 nm was measured by CO-reduced difference spectra from five all microsome preparations. The CYP2D6 forms with Pro34 --> Ser amino acid substitution were at a lower expression than CYP2D6.1 from the findings of immunoblotting and spectral analysis. The apparent K(m) values of CYP2D6.1, CYP2D6.10A, and CYP2D6.10C were 1.7, 8.5, and 49.7 microM, respectively, for bufuralol 1'-hydroxylation, and 9.0, 51.9, and 117.4 microM, respectively, for venlafaxine O-demethylation, respectively. The V(max) values were not significantly different among the three variants. These findings suggest that the decreased in vivo clearance by CYP2D6*10 was caused not only by low expression of but also the increased K(m) value of CYP2D6.
Alleles↗
Observation of a spin-flip M1 transition in 7(lambda)Li.
Using a large-acceptance germanium detector array (Hyperball), we have observed a spin-flip M1 gamma transition between the ground-state spin doublet of (7)(Lambda)Li (3/2(+)-->1/2(+)). The observed energy of 691.7+/-0.6(stat)+/-1.0(syst) keV provides crucial information on the strength of the spin-spin interaction between a Lambda and a nucleon. This is the first observation of well-identified hypernuclear gamma transitions using germanium detectors.
Journal Article↗
High expression of vascular endothelial growth factor is associated with liver metastasis and a poor prognosis for patients with ductal pancreatic adenocarcinoma.
BACKGROUND: Vascular endothelial growth factor (VEGF), a recently identified growth factor with significant angiogenic properties, is a multifunctional angiogenic cytokine that is expressed in many tumors. High VEGF expression has been shown to correlate with the incidence of metastasis and poor prognosis in various cancers. In this study, the authors investigated VEGF expression and microvessel density (MVD) in ductal pancreatic adenocarcinoma and examined the correlations among VEGF expression, clinicopathologic factors, and clinical outcome. The authors especially focused on the correlation between VEGF expression and liver metastasis. METHODS: Paraffin embedded tumor specimens of 142 surgically resected pancreas carcinoma were immunohistochemically stained for VEGF and MVD. The correlations among VEGF expression and MVD, clinicopathologic factors, and clinical outcome were then statistically analyzed. RESULTS: One hundred thirty-two (93%) of 142 ductal pancreatic adenocarcinomas were positive for VEGF protein by immunohistochemistry. A significant correlation was observed between VEGF positivity and MVD (P < 0.0001). Multivariate logistic regression analysis indicated a significant association between high VEGF expression and liver metastasis (P = 0.010) but no other factors, such as age, tumor size, histologic type, lymph node metastasis, venous invasion, neural invasion, peritoneal metastasis, or local recurrence. Patients with tumors that showed moderate or high VEGF expression had significantly shorter survival than patients with low VEGF expression or none at all in their tumors (P < 0.05). CONCLUSIONS: These results indicate that VEGF expression is closely correlated with MVD and seems to be an important predictor for both liver metastasis and poor prognosis in ductal pancreatic adenocarcinoma.
Adult↗
Novel phenylpiperazine derivatives as dual cytokine regulators with TNF-alpha suppressing and IL-10 augmenting activity.
Phenylpiperazine derivatives were synthesized as dual cytokine regulators with TNF-alpha suppressing and IL-10 augmenting activity. Lead optimization led to compound 5k having the potent regulatory activity and demonstrating remarkable protective effects against the lethal challenge of LPS in mice. suggesting that 5k would be a promising drug candidate for the treatment of TNF-alpha associated diseases including septic shock.
Animals↗