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Biomedical subjects

T Nagata

Publications and source records attributed to T Nagata.

At least 127 records · Page 7Linked to original sources
PubMed2000

Expression of OX40 and OX40 ligand (gp34) in the normal and myasthenic thymus.

OBJECTIVES: To examine the expression of OX40, an activated memory T-cell marker, and its ligand (OX40L), a set of molecules for T-cell-B-cell interaction, and other lymphocyte activation markers in the thymuses of myasthenia gravis (MG) and controls. MATERIAL AND METHODS: We studied the expression of OX40, OX40L, IL-2Ralpha and HLA-DR in the thymic tissues of MG and controls using immunocytochemistry and flowcytometry. RESULTS: In both hyperplastic thymus of MG and control thymus, OX40+ cells were scattered mainly in the medulla with much fewer OX40L+ cells being distributed in the corticomedullary junctions. IL-2Ralpha and HLA-DR were expressed in the medulla at higher frequencies as compared with OX40 in controls as well as MG. In contrast, the numbers of OX40+ cells around the germinal centers (GC) were significantly greater than those of control thymuses, and some mononuclear cells in GC were OX40L+. A considerable number of OX40+ cells were seen in the thymic tissues adjacent to thymomas. OX40+ cells were CD4+ CD8- or CD4+ CD8+ and were mostly HLA-DR-. (The coexpression of OX40 and IL-2Ralpha on activated CD4+ T cells was previously reported.) CONCLUSION: OX40, expressed in a fraction of activated CD4+ T cells, may be upregulated in thymic tissues adjacent to GC and thymoma in MG, and OX40 may interact with OX40L in GC to enhance anti-acetylcholine receptor antibody production in MG.

Adolescent↗
PubMed2000

Computed tomography and ultrasonography of metastatic cervical lymph nodes in oral squamous cell carcinoma.

OBJECTIVES: To define criteria for CT and US in differentiating cervical lymph node metastases in oral squamous cell carcinoma (SCC). MATERIALS AND METHODS: CT and/or US of 230 metastatic lymph nodes and 228 benign lymph nodes in 147 patients with oral SCC were retrospectively evaluated. The CT and US findings of each lymph node were compared with the histopathological findings. A metastasis was defined on CT as a lymph node with rim or heterogeneous enhancement, or measuring 10 mm or more in the short axis, regardless of enhancement pattern, and on US as having definite internal echoes, regardless of size, or without definite internal or hilar echoes, but measuring 10 mm or more in the short axis. A lymph node with hilar echoes or a ratio of the long to short axis (L/S ratio) of 3.5 or more was considered benign. A lymph node failing to comform to any of these categories was termed questionable. RESULTS: The positive predictive value (PPV) for CT was 90.8% and the negative predictive value (NPV) was 70.4%. However, 65.7% of all lymph nodes could not be classified as either metastastic or benign. PPV for US was 96.5% and NPV was 88.1%. 25.5% of all lymph nodes could not be classified as either metastatic or benign. CONCLUSIONS: Despite limitations in detecting metastases, by including a third category 'questionable' our criteria appear clinically more useful than other current methods based on two groups only.

Adult↗
PubMed2000

A dominant negative mutant of sar1 GTPase inhibits protein transport from the endoplasmic reticulum to the Golgi apparatus in tobacco and Arabidopsis cultured cells.

Protein secretion plays an important role in plant cells as it does in animal and yeast cells, but the tools to study molecular events of plant secretion are very limited. We have focused on the Sar1 GTPase, which is essential for the vesicle formation from the endoplasmic reticulum (ER) in yeast, and have previously shown that tobacco and Arabidopsis SAR1 complement yeast sar1 mutants. In this study, we have established a transient expression system of GFP-fusion proteins in tobacco and Arabidopsis cultured cells. By utilizing confocal laser scanning microscopy, we demonstrate that a dominant negative mutant of Arabidopsis Sar1 inhibits the ER-to-Golgi transport of Golgi membrane proteins, AtErd2 and AtRer1B, and locates them to the ER. The same mutant Sar1 also blocks the exit from the ER of a vacuolar storage protein, sporamin. These results not only provide the first evidence that the Sar1 GTPase functions in the ER-to-Golgi transport in plant cells, but also prove that conditional expression of dominant mutants of secretory machinery can be a useful tool in manipulating vesicular trafficking.

Arabidopsis↗
PubMed2000

Efficient cloning and engineering of giant DNAs in a novel Bacillus subtilis genome vector.

The Genome of Bacillus subtilis 168 was used for cloning and engineering of large-sized DNAs. A mouse genomic DNA of approximately 120 kb was cloned into a locus of the B. subtilis genome by ordered assembly of 20- to 50-kb mouse DNA segments. Cloned mouse DNA, maintained stably, was engineered through B. subtilis transformation and recombination. Creation of an I-PpoI recognition sequence at both ends of the insert facilitated its isolation by pulsed field gel electrophoresis. The basic concept of genome vector technology is suited to the handling of DNAs larger than 100 kb.

Animals↗
PubMed2000

Sulfated glycosaminoglycan synthesis and its regulation by transforming growth factor-beta in rat clonal dental pulp cells.

Dental pulps contain sulfated glycosaminoglycans (GAGs), such as chondroitin 4-sulfate (CSA/4CS), dermatan sulfate (CSB/DS), and chondroitin 6-sulfate (CSC/6CS). Sulfated GAGs play important roles in mineralization and collagen fibrillogenesis during primary, secondary, and reparative dentin formations. Transforming growth factor-beta (TGF-beta) is a potent regulator for several extracellular matrix (ECM) components and modulates the proliferation and differentiation. Using rat clonal dental pulp cells (RPC-C2A), we investigated the constituents of GAGs synthesized by the cells and the effect of TGF-beta on their synthesis by measuring the radioactivity of [35S]sulfate incorporated into GAG fractions. Cellulose acetate electrophoresis analysis revealed that RPC-C2A cells synthesized CSA and CSB but not CSC and that 10 ng/ml of TGF-beta increased the production of CSA and CSB in the cell/ECM fraction. Measurement of [35S]sulfate incorporation showed a significant increase in the amount of GAGs by TGF-beta, 1.3-fold CSA, and 1.2-fold CSB in the cell/ECM fraction. In the medium fraction the most secreted GAG was CSA, whereas CSB was stored in the cell/ECM fraction. Secreted CSA in the medium was markedly increased by 10 ng/ml of TGF-beta (1.7-fold). These findings indicate that CSA and CSB are major sulfated GAGs synthesized by RPC-C2A cells and that TGF-beta acts as a stimulator of sulfated GAG synthesis in dental pulp cells.

Animals↗
PubMed2000

Stress coping strategy in Japanese patients with eating disorders: relationship with bulimic and impulsive behaviors.

Although maladaptive coping strategies in eating disorder patients have been reported, the relationship between impulsivity and coping strategy has not previously been studied. Subjects consisted of 43 patients with anorexia nervosa restricting type (AN-R), 42 patients with anorexia nervosa binge eating/purging type (AN-BP), 71 patients with bulimia nervosa purging type (BN), and 97 controls. The Coping Inventory for Stressful Situations was used to evaluate coping strategies. Only AN-BP patients had a significantly lower task oriented-coping score than controls, and AN-R and BN patient groups used significantly less social diversion-avoidance coping strategies than controls. Emotion-oriented coping scores of AN-BP and BN patients were significantly higher than those of controls. In addition, impulsive BN patients had significantly higher emotional coping scores than less impulsive BN patients. These results suggest that maladaptive coping strategies may be a perpetuating factor even for impulsive patients and emphasizing a change in maladaptive coping strategies may be a useful treatment strategy even for highly impulsive patients.

Adaptation, Psychological↗
PubMed2000

Endothelin-1 is a potent activator of nonselective cation currents in human bronchial smooth muscle cells.

The effects of endothelin (ET)-1 on cultured human bronchial smooth muscle cells (HBSMC) were investigated and compared with those of histamine, using the patch clamp techniques and measurements of intracellular Ca(2+) ([Ca(2+)](i)). Both ET-1 and histamine caused an initial transient elevation of [Ca(2+)](i) by Ca(2+) mobilization, followed by a sustained rise due to Ca(2+) entry. Nicardipine inhibited the sustained phase, but La(3+) abolished it. With low ethyleneglycol-bis-(beta-aminoethyl ether)-N,N'-tetraacetic acid (EGTA) and K(+) internal solutions, both ET-1 and histamine induced a sustained depolarization from approximately -40 to -20 mV. Under voltage clamp conditions, both drugs transiently activated an outward K(+) current at a holding potential of 0 mV. Additionally, with a Cs(+) internal solution, they elicited another transient inward current, frequently followed by current oscillations. These transient currents were blocked by high EGTA or heparin. With high EGTA and Cs(+) internal solutions, both drugs activated a long-lasting inward current. The reversal potential of these agonist-induced currents was approximately 0 mV and was not altered by the replacement of internal or external concentration of Cl(-), suggesting that the inward current was a nonselective cation current (I(cat)). The half-maximal effective concentration to activate I(cat) was 12 nM for ET-1 and 11 microM for histamine. La(3+) and Cd(2+) abolished these agonist-induced I(cat). The effects of ET-1 on [Ca(2+)](i) and I(cat) could be blocked by combined pretreatment with BQ-123 and BQ-788. Sarafotoxin S6c also increased [Ca(2+)](i) and activated I(cat). By polymerase chain reaction of reverse transcribed RNA, we detected both ET-A and ET-B receptor messenger RNA. These results provide the first evidence that ET-1 is a potent activator of I(cat) in HBSMC via ET-A and ET-B receptors, and the activation of I(cat) plays an important role in ET-1-induced Ca(2+) entry in human airways.

Bronchi↗
PubMed2000

Aortic stent-grafting with transrenal fixation: use of newly designed spiral Z-stent endograft.

PURPOSE: To evaluate the feasibility and efficacy of a newly designed stent-graft placed across the renal arteries for exclusion of abdominal aortic aneurysms (AAAs) with short or tortuous proximal necks. METHODS: Among a group of AAA patients treated with endovascular grafting, 5 had tortuous proximal necks and 13 had necks <20 mm (mean 13 mm). In these 18 cases, a 2- to 3-cm uncovered segment of the stent-graft was placed transrenally using a catheter inserted into the renal artery as a guide for graft margin positioning. A newly designed stent-graft was constructed from a custom-made spiral Z-stent covered with a thin-walled Dacron material; the endografts were deployed through 16-F (aortoaortic model) or 18-F sheaths (bifurcated devices). Renal function was assessed by preoperative and postoperative measurement of urea nitrogen and creatinine. Aneurysm exclusion and renal artery patency were evaluated during follow-up using spiral computed tomography and angiography. RESULTS: The stent-grafts were correctly placed at the intended site in all 18 patients. Renal function was not affected except transiently in 1 patient who developed bilateral renal artery stenoses 24 hours after the procedure; Palmaz stents were deployed in each renal artery to reestablish satisfactory blood flow. Of the 33 renal arteries crossed by the bare stent-graft segment, all were patent over a mean 14-month follow-up (range 7-24), including the patient with Palmaz stents implanted for postprocedural renal stenosis. Complete aneurysm exclusion was maintained in 15 (83%) of 18 patients; proximal leaks persisted in 3 patients, including 2 with severely angled proximal necks. CONCLUSIONS: Transrenal placement of the uncovered leading edge of custom-made spiral Z-stent-based endografts appears feasible and clinically effective in the treatment of AAAs with short or tortuous proximal necks.

Aged↗
PubMed2000

Roles of hydrophobicity, protein binding and the probenecid-sensitive transport system in the cerebrospinal fluid delivery of nucleoside analogues with anti-viral activity.

Ten nucleoside analogues with anti-herpes or anti-HIV activity were investigated for their transport into the cerebrospinal fluid (CSF) following intravenous administration in rats. The novel anti-herpes agent 1-beta-D-arabinofuranosyl-2-thio-5-fluorocytosine (5F-araSC) showed the highest CSF/plasma concentration ratio (>20%), while that of acyclovir (ACV) was very low (<5%). A linear relationship was observed between the partition coefficient (chloroform/water) and CSF/unbound plasma concentration in 6 of 9 agents. The exceptions were DDI, AZT and ACV, which showed much lower concentrations in the CSF than expected from their hydrophobicity and protein binding activities. The effects of probenecid treatment on the CSF and plasma concentrations were measured with continuous intravenous administration of ACV, AZT, araC and 5F-araSC. Probenecid markedly increased the CSF concentrations of ACV and AZT, although the effect was minimal in araC and 5F-araSC. These results may provide useful information for molecular design of nucleoside analogues with better transport to the brain.

Animals↗
PubMed2000

Enzymatic reactivity and anti-tumor activity of 1-(beta-D-arabinofuranosyl)-2-thiocytosine derivatives.

Sixteen derivatives of 1-(beta-D-arabinofuranosyl)-2-thiocytosine (araSC), including five 5'-esters, three 3'-esters, five N4-amides and three 5'-phosphodiesters, were synthesized and their reactivity to mouse tissue homogenates, including plasma, liver and intestine, and antitumor activity in mice bearing P388 cells were measured. The ester derivatives had a potent effect on the enzyme systems while the amide and phosphodiester derivatives were less active. The reactivity of ester derivatives was highly dependent on their chemical structure. The reactivity of amides and phosphodiester derivatives on mouse plasma and intestinal homogenate was also dependent on the chemical structure, although their action on intestinal enzymes was very similar. Two of eight ester derivatives showed considerable antitumor activity in vivo, although they also showed serious toxicity indicated by a weight loss in the mice. Four out of five amides and two out of three phosphodiesters showed antitumor activity, and two were highly effective (>200% in T/C, the ratio of the mean survival time of the treated group to that of the control group) with only a very slight weight loss.

Animals↗
PubMed2000

DNA vaccines.

DNA vaccination or genetic immunization is a rapidly developing technology that offers new approaches for the prevention and therapy of disease. Regarding the inoculation method of DNA vaccine, we recommend the gene gun delivery system, which is a highly reliable method compared to intramuscular inoculation. DNA vaccines could have potential advantages over other types of vaccines in that these vaccines can induce strong cellular immune responses, cytotoxic T lymphocytes and type 1 helper T cells, without resorting to live organisms or complicated protein formulation. The cellular immune responses are especially required for the protection against infections with intracellular pathogens such as viruses and Mycobacterium tuberculosis and protection against cancers, suggesting that they seem to be suitable targets of DNA vaccines. We describe here that their application to bacterial infections requires optimization of codon usage in the DNA vaccines to the host animal to improve translational efficiencies of the bacteria genes. DNA vaccines for a variety of pathogens and cancers have now entered phase I/II human clinical trials.

Animals↗
PubMed2000

Stability and bioavailability of antioxidants in garland (Chrysanthemum coronarium L.).

The stability and bioavailability of the major antioxidants in garland (Chrysanthemum coronarium L.), chlorogenic acid, 3,5-dicaffeoylquinic acid and 4-succinyl-3,5-dicaffeoylquinic acid, were investigated together with caffeic acid. These compounds were stable in artificial digestive juice, but more than 90% of them disappeared from plasma within 30 min after intravenous injection into rats. When they were orally administered, only caffeic acid could be detected.

Administration, Oral↗
PubMed2000

Binding of barley and wheat alpha-thionins to polysaccharides.

An antimicrobial peptide termed BCP-2 was purified from barley grain by chitin-affinity treatment and HPLC. The results of amino acid analysis and mass spectrometry of BCP-2 indicate that the peptide is very similar to barley alpha-thionin. BCP-2 and wheat alpha1-thionin were also bound to beta-glucan but not to starch. The binding of BCP-2 to laminarin (beta-1,3-1,6-glucan) and laminarioligosaccharides was supported by fluorescence polarization data. This is the first report on the binding of alpha-thionins to polysaccharide containing chitin and beta-1,3-glucan, which construct fungal cell walls.

Antifungal Agents↗
PubMed2000

The association of calprotectin level in gingival crevicular fluid with gingival index and the activities of collagenase and aspartate aminotransferase in adult periodontitis patients.

BACKGROUND: Calprotectin, a major cytosol protein of leukocytes, exists in plasma and other body fluids of healthy human subjects. Since the calprotectin concentration rises markedly in some inflammatory diseases including rheumatoid arthritis, this protein has been thought to be a marker of inflammatory disease. Recently, we identified calprotectin in human dental calculus and gingival crevicular fluid (GCF), and found that the calprotectin concentration in GCF from patients with periodontitis was significantly higher than that in GCF from healthy subjects. In the present study, the association of GCF calprotectin level with GCF volume, gingival index (GI), and levels of biochemical markers including collagenase and aspartate aminotransferase (AST) in GCF was investigated to clarify the relationship between GCF calprotectin level and periodontal inflammation. METHODS: Ninety GCF samples collected from periodontal pockets with a probing depth of more than 4 mm in 54 patients with adult periodontitis were used for these assays. The GCF volume was measured, and GI in each site was recorded. The calprotectin content in GCF samples was determined by ELISA using a specific antibody. The activity of collagenase or AST was measured by a respective assay kit. RESULTS: The total amount of calprotectin and GCF volume showed a highly significant correlation (r = 0.64, P <0.0001), whereas the calprotectin concentration had no correlation with the GCF volume (r = 0.01, P= 0.924). The mean calprotectin concentration in GCF increased with the degree of GI, and the concentration in individual samples was significantly correlated with the GI score (r = 0.56, P<0.0001). Significant positive correlations were observed in GCF calprotectin versus collagenase (r = 0.57, P <0.0001) and GCF calprotectin versus AST levels (r = 0.40, P <0.005). CONCLUSIONS: From the present results and our previous findings, it is shown that the GCF calprotectin level significantly correlates not only with clinical indicators but also with current biochemical marker levels and that calprotectin may be a useful marker for periodontal inflammation.

Adult↗
PubMed2000

Mast cells are not involved in the development of cyclosporin A-induced gingival hyperplasia: a study with mast cell-deficient mice.

BACKGROUND: A previous study suggested that mast cells (MC) are involved in the development of cyclosporin A-induced gingival hyperplasia, since an increased number of MC were observed in the tissue sections of enlarged gingiva. To determine the role of MC in gingival hyperplasia, an MC-deficient mouse model was used in the current study. METHODS: MC-deficient mice (WBB6F1xW/Wv) and their littermates (+/+) were fed sucrose-containing diets supplemented with or without varying concentrations (300, 400, 500, 600 mg) of cyclosporin A/kg of diet. After 30 days, the mice were sacrificed and the degree of gingival hyperplasia was evaluated by the appearance of the gingiva. Tissue MC were stained with toluidine blue to confirm the presence or absence of MC in the enlarged gingiva. RESULTS: Both W/Wv and +/+ mice, when fed with 600 mg cyclosporin A/kg diet for 30 days, exhibited a similar degree of gingival hyperplasia, while other test mice or control mice did not. Toluidine blue staining of the tissue sections confirmed the presence of MC in the enlarged gingiva of the +/+ mice, but not the W/Wv mice. CONCLUSIONS: These results indicate that mast cells are not necessary in the development of cyclosporin A-induced gingival hyperplasia, and that the increased number of MC observed in the enlarged gingiva may be a secondary effect of gingival hyperplasia. We also conclude that a study of mice lacking certain molecules or cells would be quite useful in determining the molecules or cell types responsible for the pathogenesis of drug-induced gingival hyperplasia.

Animals↗
PubMed2000

Cryofiltration and oral corticosteroids provide successful treatment for an elderly patient with cryoglobulinemic glomerulonephritis associated with hepatitis C virus infection.

A 75-year-old man was admitted due to nephrotic syndrome, purpura on the legs, which was associated with hepatitis C virus (HCV), and type II mixed cryoglobulinemia. Renal biopsy revealed features of cryoglobulinemic glomerulonephritis. Since the patient was elderly and the HCV genotype was Ib, interferon-alpha for reducing HCV was not indicated. Four sessions of cryofiltration and the administration of corticosteroids improved the proteinuria and renal function strikingly without adverse effects. This case demonstrates that an elderly patient who has nephrotic syndrome caused by cryoglobulinemic glomerulonephritis associated with HCV can be treated safely by cryofiltration with low doses of oral corticosteroids.

Adrenal Cortex Hormones↗
PubMed2000

[A case of rhabdomyolysis with water intoxication confirmed by muscle biopsy].

A 32-year-old woman with chronic schizophrenia who took 8-10 liters of water for three years due to thirsty, admitted to our hospital because of convulsion and muscle weakness. Neurological finding on admission showed a mild disturbance of consciousness, moderate proximal muscle weakness, and muscle pain. Laboratory examination revealed marked serum hyponatremia(102 mEq/l) and high value of creatin kinase (1,259 IU/l). The level of creatin kinase reached a peak(39,700 IU/l) at the 5th hospital day. An analysis of the muscle biopsy specimen showed necrotic muscle fibers and opaque fibers, that was compatible with rhabdomyolysis. T 2 weighted magnetic resonance imaging of the brain showed a transient high signals in bilateral putamen but not in pons. She was diagnosed to have rhabdomyolysis due to water intoxication. The present case is the first rhabdomyolysis in Japan that was confirmed by muscle biopsy at an acute stage of water intoxication related with schizophrenia.

Adult↗