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Biomedical subjects

T Nagata

Publications and source records attributed to T Nagata.

At least 145 records · Page 8Linked to original sources
PubMed2000

[Simulation of night myopia in pseudophakic eyes].

PURPOSE: Eyes with an intraocular lens (IOL) implanted that have no accommodative ability are likely to have night myopia caused by Purkinje's shift and chromatic aberration. We evaluated the changes in retinal images caused by night myopia in various IOL-implanted eyes by simulation using model eyes. METHODS: A polymethylmethacrylate (PMMA) IOL, soft acrylic IOLs, and high-refractive-index silicone IOLs were prepared, and inserted into the model eye. The image plane of the model eye was determined as the line image at which a slit light of 560 nm was best focused, which was regarded as emmetropic condition under photopic vision. A slit light of 505 nm was then directed into the model eye. Its line image on the image plane was blurred, which was regarded as myopic condition under scotopic vision. Under each condition, the modulation transfer functions (MTF) were calculated and the line images were photographed. RESULTS: The degree of reduction of MTF and blurring of the line image under the night myopic condition was in the order of PMMA < soft acrylic < high refractive index silicone IOL. CONCLUSION: Eyes with a soft acrylic or high-refractive-index silicone IOL may have more intense night myopia caused by chromatic aberration.

Cataract↗
PubMed2000

Thymidylate synthase expression correlates closely with E2F1 expression in colon cancer.

Thymidylate synthase (TS) is thought to be one of the target genes that the E2F1 transcription factor binds to and regulates. However, the relationship between the expressions of TS and E2F1 in primary colon cancer specimens remains unclear. The aim of this study was to define the relation of TS and E2F1 gene expressions in tumor samples from 23 colon cancer patients. TS and E2F1 gene expressions were measured by TaqMan reverse transcription-PCR assay using glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as an internal standard and expressed as a TS:GAPDH or E2F1:GAPDH mRNA ratio. A close relationship was found between TS gene expression and E2F1 gene expression (r2 = 0.598, P < 0.001) in 23 tumor samples analyzed. Surprisingly, a high correlation between TS gene expression and E2F1 gene expression was observed even in advanced tumors from stage IV colon cancer patients. These results suggest that transcription of the TS gene may be regulated by E2F1 in primary colon cancer specimens and that this gene-regulatory pathway from E2F1 to TS may be highly conserved during malignant progression. Four of the 23 patients showed TS overexpression with increased E2F1 expression. These results suggest that the ability of a tumor to increase TS expression may possibly be due to an overexpression of E2F1. Although the number of patients was relatively small, our study provides new insights into the molecular mechanisms underlying the regulation of TS expression in colon cancers.

Adult↗
PubMed2000

[Prognostic significance of chromosome analysis in childhood acute lymphoblastic leukemia. Children's Cancer and Leukemia Study Group (CCLSG)].

We analyzed the prognostic significance of chromosomal findings in children with acute lymphoblastic leukemia (ALL), treated according to the Children's Cancer and Leukemia Study Group protocols between 1987 and 1993. Patients were classified into 5 groups according to chromosome number. The patients with a hyperdiploid(> 50) karyotype(13%) had the best prognosis [4-year event-free survival (EFS): 83 +/- 6%], while those with a pseudodiploid karyotype (24%) had the worst prognosis(4-year EFS: 52 +/- 6%) (log-rank, p = 0.03). However, multivariate analysis revealed that the ploidy classification had no prognostic significance in terms of EFS. When patients were classified according to chromosome abnormalities, those with any type of translocation had a worse outcome (4-year EFS: 33 +/- 9%) than those with hyperdiploidy(> 50), normal diploidy, and other abnormalities(log-rank, p < 0.0001). Multivariate analysis revealed that chromosome abnormalities were an independent prognostic factor (relative risk 3.98; p < 0.0001). Patients with t(1; 19) had an EFS similar to that of patients with chromosome abnormalities other than translocations or normal diploidy. We conclude that chromosomal findings have prognostic significance, although some chromosome abnormalities lost their statistical significance after modern intensified chemotherapy. Childhood ALL should be further stratified according to chromosome classification.

Child↗
PubMed2000

[Bronchial atresia with atelectasis of the left upper lobe].

A 69-year-old woman visited her physician on October 1 complain of dry cough. However, the chest radiograph revealed no abnormalities. She was later admitted to our hospital because a radiograph taken by another physician on November 26 revealed a massive lesion in the right upper mediastinum. Computed tomographic findings showed a massive lesion containing a branching structure with a few calcifications, suggesting a case of atelectasis of the left upper lobe with mucus plug. Bronchoscopic examination revealed complete obstruction of the orifice of the left upper lobe bronchus, and so a diagnosis of bronchial atresia was made. However, since the patient had a history of tuberculous peritonitis and the mass lesion was somewhat calcified, the possibility that this was an acquired case could not be ruled out. After treatment with oral antibiotics, the size of the atelectasis was decreased. Therefore, we considered that the expansion of the atelectasis could have been due to superimposed bacterial infection.

Aged↗
PubMed2000

Metabolism of ginsenoside Rg1 by intestinal bacteria. II. Immunological activity of ginsenoside Rg1 and Rh1.

AIM: To compare the effect of ginsenoside Rg1 and its metabolite Rh1 on proinflammatory cytokines and their mRNA expression by THP-1 cells. METHODS: Human peripheral blood mononuclear cells (PBMC) were incubated with Rg1 and Rh1 at concentrations of 0.1, 1, 10, and 100 mg/L, and the cell proliferation was measured 24 h after incubation. Radioimmunoassay (RIA) was used to detect the production of proinflammatory cytokines, TNF alpha, IL-1 alpha, and IL-8. TNF alpha mRNA level was detected by reverse transcription polymerase chain reaction (RT-PCR) after administration of Rg1 and Rh1. RESULTS: Rg1 and Rh1 (at concentration of 0.1, 1, 10, 100 mg/L) had no effect on PBMC proliferation. Rh1 1 mg/L could upregulate the productions of TNF (and IL-8 induced by lipopolysaccharides (LPS) 10 mg/L plus phorbol myristate acetate (PMA) 200 nmol/L, however, Rg1 showed an inhibitory effect on TNF alpha production induced by LPS 100 mg/L. Rg1 1 mg/L and Rh1 100 mg/L enhanced the production of IL-1 alpha level in THP-1 cells in the presence of LPS 10 mg/L. RT-PCR revealed that Rh1 stimulated TNF alpha mRNA expression in suitable stimulatory conditions. CONCLUSION: Rg1 and Rh1 have different effects on the production of cytokines produced THP-1 cells stimulated by LPS and PMA.

Ginsenosides↗
PubMed2000

Effects of polysaccharides (FI0-b) from mycelium of Ganoderma tsugae on proinflammatory cytokine production by THP-1 cells and human PBMC (I).

AIM: To compare the effects of water-soluble polysaccharides, FI0-b, and its formic acid-modified derivative, FI0-b-H, on production of human proinflammatory cytokines. METHODS: The polysaccharides were modified by formic acid. Cytokine production was quantitated by radioimmunoassay. mRNA for cytokines was measured by semi-quantitative RT-PCR. RESULTS: FI0-b and FI0-b-H 4, 40, and 400 mg/L significantly downregulated interleukin-1 alpha (IL-1 alpha) production by THP-1 cells induced by lypopolysaccharide (LPS) 1 or 10 mg/L and phorbol myristate acetate (PMA) 200 nmol/L. At lower stimulation with LPS 10 mg/L and PMA 200 nmol/L, both polysaccharides significantly upregulated tumor necrosis factor alpha (TNF alpha) production by THP-1 cells. However, at higher stimulation with LPS 100 mg/L and PMA 200 nmol/L, they downregulated TNF alpha production. FI0-b-H downregulated interleukin-8 (IL-8) production by THP-1 cells at a lower-dose of LPS 1 mg/L and PMA 200 nmol/L, but upregulated IL-8 production at a higher-dose of LPS 10 mg/L and PMA 200 nmol/L. Production of cytokines (IL-1 alpha and TNF alpha) was transcriptionally or post-transcriptionally regulated by FI0-b and FI0-b-H. CONCLUSION: The water-soluble polysaccharides of Ganoderma tsugae mycelium have bidirectional immunomodulatory effects on cytokine production in different stimulatory conditions in a dose-dependent manner. Compared with FI0-b, FI0-b-H has more marked effects on human proinflammatory cytokine production.

Adult↗
PubMed2000

Effects of polysaccharides (FI0-c) from mycelium of Ganoderma tsugae on proinflammatory cytokine production by THP-1 cells and human PBMC (II).

AIM: To study the effects of water-soluble polysaccharides. FI0-c, and its sulfated derivative, FI0-c-S, on production of human proinflammatory cytokines, interleukin-1 alpha (IL-1 alpha) and tumor necrosis factor alpha (TNF alpha). METHODS: The herbal polysaccharides were modified by chlorosulfornic acid in dimethyl sulfoxide (Me2SO). Cytokine production was measured by radioimmunoassay, mRNA for the cytokines was measured by semi-quantitative RT-PCR. RESULTS: FI0-c 4 mg/L itself induced IL-1 alpha production by THP-1 cells without stimulants, such as lipopolysaccharides (LPS) and phorbol myristate acetate (PMA). On the other hand, FI0-c and FI0-c-S inhibited the IL-1 alpha production by THP-1 cells with these stimulants. FI0-c and FI0-c-S significantly upregulated TNF alpha production by THP-1 cells without stimulants or at a low dose of LPS 10 mg/L and PMA 200 nmol/L, whereas these polysaccharides markedly downregulated the TNF alpha production by a high dose of LPS 100 mg/L and PMA. Human peripheral blood mononuclear cells (PBMC) responded to FI0-c and FI0-c-S in IL-1 alpha and TNF alpha production in a fashion similar to THP-1 cell responses. FI0-c 4 mg/L downregulated high-dose LPS- and PMA-induced IL-1 alpha or TNF alpha mRNA and their protein production by THP-1 cells. CONCLUSION: The water-soluble polysaccharides of Ganoderma tsugae mycelium have bidirectional immunomodulatory effects on cytokine production in different cell stimulatory conditions. Chemical modification of this polysaccharide changed the intensity of regulatory effect on cytokine production.

Adult↗
PubMed1999

Correlation of glutamate-induced apoptosis with caspase activities in cultured rat cerebral cortical neurons.

In cultured rat cortical neurons lactate dehydrogenase (LDH) activity in the medium, a cell-death marker, increased gradually after exposure to glutamate (100 microM to 1 mM) for 60 min and reached a plateau at 24 to 30 h. Neuronal death was mainly apoptotic as suggested by typical electron microscopic findings, fluorescent double staining with membrane-permeating and nonpermeating chromatin dyes, nick end labeling, and assessment of DNA fragmentation by agarose gel electrophoresis. After 1 mM glutamate exposure, a rise of interleukin-1beta converting enzyme (ICE)-like protease activity in neurons was parallel to cysteine protease p32 (CPP32)-like protease activity and declined before CPP32-like protease activity reached the peak (at 6 h). LDH activity in the medium of glutamate-exposed neurons was decreased by specific ICE and/or CPP32 inhibitors, acetyl-L-tyrosyl-L-valyl-L-alanyl-L-aspart-1-al (Ac-YVAD-CHO) and acetyl-L-aspartyl-L-glutamyl-L-valyl-L-aspart-1-al (Ac-DEVD-CHO), respectively, in a dose-dependent manner. Fluorescent double staining of nuclei also demonstrated that at 100 microM each inhibitor prevented neuronal apoptosis and that this effect was additive. Among agonists corresponding to various glutamate receptor subtypes, N-methyl-D-aspartate (NMDA) and kainate induced apoptosis in cortical neuronal cultures while alpha-amino-3-hydroxy-5-methylisoxazole-4-propinate (AMPA) did not. The metabotropic glutamate receptor agonist, 1-aminocyclopentane-1S, 3R-dicarboxylate (ACPD) prevented apoptosis. Interestingly, apoptosis at 24 h after agonist or antagonist exposure correlated closely with caspase activity 6 h after exposure.

Animals↗
PubMed1999

Nicergoline enhances glutamate re-uptake and protects against brain damage in rat global brain ischemia.

Whereas a 2-3 degrees C decrease in intraischemic brain temperature can be neuroprotective, mild brain hyperthermia significantly worsens outcome. Our previous study suggested that an ischemic injury mechanism which is sensitive to temperature may not actually increase the extracellular glutamate concentration ([Glu](e)) during the intraischemic period, but rather impairs the Glu re-uptake system, which has been suggested to be involved in the reversed uptake of Glu. We speculated that enhancing Glu re-uptake, pharmacologically or hypothermically, may shorten exposure to high [Glu](e) in the postischemic period and thereby decrease its deleterious excitotoxic effect on neuronal cells. In the present study, rats treated with nicergoline (32 mg/kg, i.p.), an ergot alkaloid derivative, showed minimal inhibition of the [Glu](e) elevation which characteristically occurs during the 10-min intraischemic period, while Glu re-uptake was dramatically improved in the postischemic period, when severe transient global ischemia was caused by mild hyperthermia. Moreover, the nicergoline (32 mg/kg, i.p.) treated rats showed reduced cell death morphologically and clearly had a far lower mortality. The present study suggests that the development of therapeutic strategies aimed at inhibition or prevention of the reversed uptake of glutamate release during ischemia, i.e., activation of the glutamate uptake mechanism, is a promising approach to reduce neural damage occurring in response to brain ischemia.

Adrenergic alpha-Antagonists↗
PubMed1999

Karyotypic analyses of hepatoblastoma. Report of two cases and review of the literature suggesting chromosomal loci responsible for the pathogenesis of this disease.

Two cases of fetal hepatoblastoma with unique karyotypic changes are described. One was a 17-month-old boy with multiple unbalanced chromosomal translocations, resulting in four types of derivative chromosomes involving chromosomal loci at 1q21, 1q32, 2q23, 6q27, 7p22, and 21p12, partial tetrasomy of 1q, partial trisomy of 2q, and partial monosomy of 21p. The clonal karyotype of this tumor was 46,XY,der(2)t(1;2)(q32;q37), der(6)t(1;6)(q12;q27), der(7)t(2;7)(q23;p22), der(21)t(2;21) (q23;p12). In the other case, a 4-year-old girl, karyotypic analyses revealed trisomy 2 and 8, and the clonal karyotype of this case was 48,XX,+2,+8. Review of these cases together with previous reports suggested the significance of chromosomal changes including numerical abnormalities of 1q, 2(or 2q), 20, and 8 (or 8q), and breakage of 1q and 2q in the development of hepatoblastoma. The results presented herein underscore the significance of numerical abnormalities of chromosomal regions 1q and 2q and of chromosome 8 in the development of hepatoblastoma, in addition to abnormalities of 6q27, 7p22, and 21p12-13 as other chromosomal loci that may be responsible for the pathogenesis of this embryonal type of tumor.

Child, Preschool↗
PubMed1999

Fractionation of apple procyanidins by size-exclusion chromatography.

Oligomeric constituents of apple procyanidins were fractionated by size-exclusion chromatography using a TSKgel Toyopearl HW-40F column. The best separation was obtained using a mobile phase of acetone-8 M urea (6:4; adjusted to pH 2) at a flow-rate of 1.0 ml/min. In this chromatographic system, the use of 8 M urea in the mobile phase resulted in a molecular sieve effect without any surface affinity interaction between the gel beads and the procyanidin molecules. Each fraction obtained was examined by reversed-phase high-performance liquid chromatography and time-of-flight mass spectrometry. The order of elution of the procyanidins from the column was coincident with their degree of polymerization.

Biflavonoids↗
PubMed1999

Codon optimization effect on translational efficiency of DNA vaccine in mammalian cells: analysis of plasmid DNA encoding a CTL epitope derived from microorganisms.

Interspecific difference of codon usage is one of the major obstacles for effective induction of specific immune responses against bacteria and protozoa by DNA immunization. Using genes encoding major histocompatibility complex class I-restricted cytotoxic T-lymphocyte (CTL) epitopes, derived from an intracellular bacterium, Listeria monocytogenes and a mouse malaria parasite, Plasmodium yoelii, we report here that the codon optimization level of the genes is not precisely proportional to, but does correlate well with the translational efficiency in mammalian cells, which is concomitantly associated with the induction level of specific CTL response in the mouse. These results suggest that DNA immunization using the gene codon-optimized to mammals through the entire region is very effective.

Animals↗
PubMed1999

Structure, backbone dynamics and interactions with RNA of the C-terminal RNA-binding domain of a mouse neural RNA-binding protein, Musashi1.

Musashi1 is an RNA-binding protein abundantly expressed in the developing mouse central nervous system. Its restricted expression in neural precursor cells suggests that it is involved in the regulation of asymmetric cell division. Musashi1 contains two ribonucleoprotein (RNP)-type RNA-binding domains (RBDs), RBD1 and RBD2. Our previous studies showed that RBD1 alone binds to RNA, while the binding of RBD2 is not detected under the same conditions. Joining of RBD2 to RBD1, however, increases the affinity to greater than that of RBD1 alone, indicating that RBD2 contributes to RNA-binding. We have determined the three-dimensional solution structure of the C-terminal RBD (RBD2) of Musashi1 by NMR. It folds into a compact alpha beta structure comprising a four-stranded antiparallel beta-sheet packed against two alpha-helices, which is characteristic of RNP-type RBDs. Special structural features of RBD2 include a beta-bulge in beta2 and a shallow twist of the beta-sheet. The smaller 1H-15N nuclear Overhauser enhancement values for the residues of loop 3 between beta2 and beta3 suggest that this loop is flexible in the time-scale of nano- to picosecond order. The smaller 15N T2 values for the residues around the border between alpha2 and the following loop (loop 5) suggest this region undergoes conformational exchange in the milli- to microsecond time-scale. Chemical shift perturbation analysis indicated that RBD2 binds to an RNA oligomer obtained by in vitro selection under the conditions for NMR measurements, and thus the nature of the weak RNA-binding of RBD2 was successfully characterized by NMR, which is otherwise difficult to assess. Mainly the residues of the surface composed of the four-stranded beta-sheet, loops and C-terminal region are involved in the interaction. The appearance of side-chain NH proton resonances of arginine residues of loop 3 and imino proton resonances of RNA bases upon complex formation suggests the formation of intermolecular hydrogen bonds. The structural arrangement of the rings of the conserved aromatic residues of beta2 and beta3 is suitable for stacking interaction with RNA bases, known to be one of the major protein-RNA interactions, but a survey of the perturbation data suggested that the stacking interaction is not ideally achieved in the complex, which may be related to the weaker RNA-binding of RBD2.

Amino Acid Sequence↗
PubMed1999

Structure and interactions with RNA of the N-terminal UUAG-specific RNA-binding domain of hnRNP D0.

Heterogeneous nuclear ribonucleoprotein (hnRNP) D0 has two ribonucleoprotein (RNP)-type RNA-binding domains (RBDs), each of which can bind solely to the UUAG sequence specifically. The structure of the N-terminal RBD (RBD1) determined by NMR is presented here. It folds into a compact alphabeta structure comprising a four-stranded antiparallel beta-sheet packed against two alpha-helices, which is characteristic of the RNP-type RBDs. Special structural features of RBD1 include N-capping boxes for both alpha-helices, a beta-bulge in the second beta-strand, and an additional short antiparallel beta-sheet coupled with a beta-turn-like structure in a loop. Two hydrogen bonds which restrict the positions of loops were identified. Backbone resonance assignments for RBD1 complexed with r(UUAGGG) revealed that the overall folding is maintained in the complex. The candidate residues involved in the interactions with RNA were identified by chemical shift perturbation analysis. They are located in the central and peripheral regions of the RNA-binding surface composed of the four-stranded beta-sheet, loops, and the C-terminal region. It is suggested that non-specific interactions with RNA are performed by the residues in the central region of the RNA-binding surface, while specific interactions are performed by those in the peripheral regions. It was also found that RBD1 has the ability to inhibit the formation of the quadruplex structure.

Amino Acid Sequence↗
PubMed1999

Lymphocyte subset, lymphocyte proliferative response, and soluble interleukin-2 receptor in anorexic patients.

BACKGROUND: Despite a prominent malnourished state, anorexics are unexpectedly free from infection. Several studies have shown that the cell-mediated immunity of anorexics might be well preserved, but results are conflicting. METHODS: Lymphocyte subsets, lymphoproliferative response to phytohemagglutinin, and soluble interleukin-2 receptor (sIL-2R) were measured in 7 patients with anorexia nervosa restricting type (RAN), 6 with anorexia nervosa binge-eating/purging type (ANBP), and 8 controls (C). RESULTS: Compared with controls, significantly elevated percentage of CD4 and CD4/CD8 ratio in ANBP was found. Although there was no significant difference in lymphoproliferative response among the three groups, sIL-2R in RAN was significantly lower than that in the C group, but not in ANBP. CONCLUSIONS: Although detail mechanism still remains to be unknown, some kinds of compensatory mechanism for cell-mediated immunity is working, especially in chronic underweight anorexic patients.

Adult↗
PubMed1999

Altered body fat distribution after recovery of weight in patients with anorexia nervosa.

OBJECTIVE: This study investigated the changes in regional body composition such as bone mineral content, lean body mass, and fat mass in patients with anorexia nervosa before and after weight gain. METHODS: Body composition was measured before and after weight gain by dual photon absorptiometry in 21 female patients who met the DSM-III-R criteria. RESULTS: Soft mass of the pelvis, trunk, and upper and lower extremities in patients with anorexia nervosa was remarkably reduced to less than 70% of standard body weight. After restoring normal weight, soft mass of the pelvis and trunk increased remarkably and reached the levels of controls, but the soft mass in the upper and lower extremities remained below the control level. As a result, patients with anorexia nervosa demonstrated central obesity after weight recovery. DISCUSSION: We briefly discussed the cause of the altered fat distribution, such as central obesity, in patients with anorexia nervosa after weight recovery.

Adipose Tissue↗
PubMed1999

Splenic artery aneurysm associated with systemic lupus erythematosus: report of a case.

We herein report on a 64-year-old Japanese female patient who presented with a splenic artery aneurysm (SAA) associated with systemic lupus erythematosus (SLE). The saccular aneurysm, which measured 3 cm in diameter, was located in the proximal third of the splenic artery from the pancreas with a portosystemic shunt. A double ligation of the splenic artery (the distal and proximal sides of the aneurysm) was performed without a splenectomy. The postoperative course showed acute pancreatitis without either splenic infarction or portal thrombus. To our knowledge, the closed association of SLE with an aneurysmal dilatation of the splenic artery has not been previously reported. Both the pathogenesis and the management of SAA associated with SLE are discussed following the presentation of this case. This is the first reported case of SAA associated with SLE.

Aneurysm↗