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Biomedical subjects

T Nagata

Publications and source records attributed to T Nagata.

At least 91 records · Page 5Linked to original sources

Protective cytotoxic T lymphocyte responses induced by DNA immunization against immunodominant and subdominant epitopes of Listeria monocytogenes are noncompetitive.

Taking advantage of the fact that plasmid DNA encoding a single cytotoxic T lymphocyte (CTL) epitope can induce CTLs, we examined the influence of T-cell responses to dominant epitopes on those to a subdominant epitope derived from Listeria monocytogenes. Our data suggest that interaction between T cells against dominant and subdominant epitopes does not operate in the generation of the hierarchy. Furthermore, we found that a single dominant epitope is sufficient for the induction of protective immunity.

3T3 Cells↗

Moxibustion treatment of breech presentation.

Breech presentation was successfully corrected by stimulating acupuncture points with moxibustion or low-frequency electrical current. Only patients with breech pregnancies at the 28th week or later were entered into the study. With moxibustion treatment, the control group had a spontaneous correction rate of 165/224 (73.66%), and the treatment group had a correction rate of 123/133 (92.48%) (P<0.0001, x2 test). With low-frequency percutaneous electrical stimulation, the correction rate was 20/941 (83.87%) in the control group and 171/191 (89.52%) in the treatment group (P=0.094, x2 test). The controls in the moxibustion study did no exercises and received no external manipulation to correct breech presentation whereas those in the electrical stimulation study experienced both. Acupuncture stimulation, especially with moxibustion, is expected to serve as a safe and effective modality in the management of breech presentation in a clinical setting.

Acupuncture Points↗

A role of ghrelin in neuroendocrine and behavioral responses to stress in mice.

Ghrelin, an endogenous ligand of the growth hormone secretagogue receptor, was recently identified in the rat stomach. Previous studies have shown that ghrelin potently increases growth hormone release and food intake. We examined the effects of the gastric peptide ghrelin on anxiety-like behavior in association with the hypothalamic-pituitary-adrenal axis in mice. Both intra-third cerebroventricular and intraperitoneal administration of ghrelin potently and significantly induced anxiogenic activities in the elevated plus maze test. Ghrelin gene expression in the stomach was increased by tail pinch stress as well as by starvation stress. Administration of a corticotropin-releasing hormone (CRH) receptor antagonist significantly inhibited ghrelin-induced anxiogenic effects. Peripherally administered ghrelin significantly increased CRH mRNA, but not urocortin mRNA expression in the hypothalamus. Furthermore, intraperitoneal injection of ghrelin produced a significant dose- dependent increase in serum corticosterone levels. These findings suggest that ghrelin may have a role in mediating neuroendocrine and behavioral responses to stressors and that the stomach could play an important role, not only in the regulation of appetite, but also in the regulation of anxiety.

Animals↗

Stent-Graft treatment of dissecting aneurysm in association with aortic intramural hematoma: when should the procedure be performed?

PURPOSE: To report 2 cases of stent-graft implantation for localized dissecting aneurysm during the conservative treatment of aortic intramural hematoma. CASE REPORTS: One patient underwent stent-graft implantation for 2 localized dissecting aneurysms about 23 months after symptom onset. Computed tomography (CT) 1 year after the procedure demonstrated aneurysm shrinkage. In the other patient, a localized dissecting aneurysm was treated about 3 months after symptom onset, even though the intramural hematoma had not resolved. CT scanning 3 months after the procedure demonstrated aneurysm shrinkage, but also revealed poor attachment of the distal stent-graft to the aortic wall due to subsequent resolution of the hematoma. CONCLUSIONS: Endograft implantation for treatment of localized dissecting aneurysm associated with aortic intramural hematoma should probably not be performed before the hematoma has completely resolved.

Aortic Dissection↗

[Cytotoxic activity and cytokine gene induction of Asp-hemolysin to vascular endothelial cells].

We examined the effects of Asp-hemolysin from Aspergillus fumigatus Fresenius-Muramatsu strain on the viability and cytokine gene expression of human umbilical vein endothelial cells (HUVEC). The cell viability of HUVEC was reduced to 50% by 100 micrograms/ml of Asp-hemolysin. However, lower concentration of Asp-hemolysin (< 30 micrograms/ml) had no effect on the cell viability. The mRNA expression of such cytokines as tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1 beta, IL-6, IL-8 and granulocyte-macrophage colony stimulating factor (GM-CSF) were also observed in HUVEC cultured with 30 micrograms/ml of Asp-hemolysin.

Cells, Cultured↗

[Effects of low density lipoprotein and oxidized low density lipoprotein on the cytotoxic activity of Asp-hemolysin to murine macrophages].

We examined the effects of human low density lipoprotein (LDL) and oxidized LDL (Ox-LDL) on the cytotoxic activity of Asp-hemolysin from Aspergillus fumigatus Fresenius-Muramatsu strain to mouse peritoneal macrophages (M phi). The inhibitory effects of LDL and Ox-LDL on the cytotoxic activity of Asp-hemolysin to M phi increased in a dose-dependent manner, and the effect of Ox-LDL was greater than the inhibitory effect of LDL. Furthermore, the binding of Asp-hemolysin to LDL or Ox-LDL was observed by western blot analysis of the culture medium. These results suggest that the inhibition by LDL or Ox-LDL on the cytotoxic activity of Asp-hemolysin to M phi was due to the binding of LDL or Ox-LDL to Asp-hemolysin in the culture medium.

Animals↗

Synthesis of calcitonin gene-related peptide (CGRP) by rat arterial endothelial cells.

We investigated the protein and mRNA expression of calcitonin gene-related peptide (CGRP) in endothelial cells of the rat thoracic aorta and femoral artery. Light microscopic immunocytochemistry revealed that immunoreactivity for CGRP was preferentially located in the endothelium of both vessels. Immunoelectron microscopy showed that CGRP-immunoreactive gold particles were preferentially localized on cisterns of the rough endoplasmic reticulum and on the Weibel-Palade (WP) bodies in the endothelial cells. Prepro CGRP mRNA signals were also detected on the endothelium. Our results are the first to demonstrate that endothelial cells of both elastic and large muscular arteries synthesize CGRP and store it, in part, in WP bodies, implying that CGRP may act as an endothelium-derived relaxing factor in these vessels.

Animals↗

Nifedipine induces gingival overgrowth in rats through a reduction in collagen phagocytosis by gingival fibroblasts.

BACKGROUND: Nifedipine is used as a long-acting vasodilator, and a primary side effect is the induction of gingival overgrowth, which is characterized by an accumulation of collagenous components within the gingival connective tissue. To elucidate the mechanisms of nifedipine-induced gingival overgrowth, we investigated the effect of nifedipine on Type I collagen metabolism in the gingiva of rats. METHODS: Twenty-day-old rats were fed a powdered diet containing or lacking nifedipine for 3 to 55 days. Immunohistochemical analysis with anti-Type I collagen antibody was employed to examine the density of Type I collagen in the gingival connective tissue. Total RNAs were isolated from mandibular molar gingiva on days 0, 3, 15, 30, and 55, and reverse transcription polymerase chain reaction was performed to investigate the mRNA levels of Type I collagen. In addition, we performed a flow cytometric analysis with collagen-coated latex beads and cultured fibroblasts derived from rat gingiva to measure collagen phagocytosis. RESULTS: Immunohistochemical analysis revealed that Type I collagen was more prevalent in the connective tissue of nifedipine-treated gingiva than in controls on day 55. In the nifedipine-treated group, the expression of Type I collagen mRNA gradually decreased to 1.5% on day 55 compared to day 0. In the control group, Type I collagen mRNA also decreased to 32%; however, mRNA expression was significantly lower in the nifedipine-treated group than in the controls. When the rate of phagocytic cells derived from nifedipine-treated gingiva and controls was represented as the mean +/- SE of the percentage from 3 different experiments, the values were as follows: on day 15, 13.5 +/- 2.1% and 15.0 +/- 1.5%; on day 30, 12.2 +/- 4.3% and 34.5 +/- 6.7% in the nifedipine-treated and the control group, respectively, indicating that phagocytic cells were considerably fewer in the nifedipine-treated gingiva on day 30. This finding demonstrates that the decrease in phagocytosis caused by nifedipine appeared before the detection of severe macroscopic gingival overgrowth. CONCLUSION: These findings suggest that the decrease in collagen degradation due to lower phagocytosis is closely associated with the increase in Type I collagen accumulation in nifedipine-treated rat gingiva.

Animals↗

Microscopic polyangiitis associated with sinobronchial syndrome.

A woman with a long history of chronic bronchitis and chronic sinusitis, i.e., sinobronchial syndrome, was admitted with a fever. Radiologically, there were areas of longstanding consolidation in both lungs, with areas of active inflammation demonstrated by gallium-67 scintigraphy. Antineutrophil cytoplasmic antibody specific for myeloperoxidase was highly positive. Pulmonary hemorrhage and hematuria occurred 2 weeks after admission and responded to steroid therapy. However, the patient died of pneumonia. An autopsy revealed systemic necrotizing vasculitis affecting multiple organs, consistent with microscopic polyangiitis. The vasculitis might have been caused by the chronic inflammation in the lungs associated with sinobronchial syndrome.

Aged↗

[Breast cancer].

Neoadjuvant chemotherapy (NAC) represents a new approach based on sound theoretical, pharmacokinetic, and experimental principles. The purpose of NAC is to improve control of the primary site by downstaging and to improve control of micrometastatic disease. NAC has been standard therapy in the management of locally advanced breast cancer. Patients with earlier stage breast cancer may also benefit from treatment with NAC. Recently some investigators have mentioned that NAC can be used instead of adjuvant chemotherapy and would be most appropriate for patients who wish to preserve their breast but who have tumors too large for breast conserving surgery. In this article, we reviewed the present status of NAC (indication, clinical response, pathologic response, survival, possibility of breast conservation, prognostic/predictive factors, neoadjuvant endocrine therapy) and discussed several unanswered questions on NAC (survival benefit, optimal number of treatment cycles, optimal regimens) and future direction. Combined modality therapy including NAC appears to provide excellent local control, the possibility of breast conservation, and, probably, an increased survival rate, at least for some subsets of patients. Furthermore, through sequential sampling, NAC provides indeed the opportunity to identify molecular mechanisms associated with pathologic response and to study the possibility to guide the choice for induction treatment and patient populations submitted to neoadjuvant chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗

[An autopsy case of atypical Friedreich's ataxia with chronic idiopathic intestinal pseudo-obstruction].

We report a 58-year-old man with slowly progressive muscle atrophy and weakness in the four extremities, accompanying cerebellar ataxia and sensory impairment of all modalities. He was a product of consanguineous marriage. His neurological manifestations began in childhood. He was admitted to our hospital because of marked abdominal distension and pretibial edema with hypoalbuminemia and hyperlipidemia. Neuroimaging studies showed marked atrophy of the cerebellum and spinal cord. Nerve conduction studies presented with slowing and sural nerve biopsy revealed demyelination with onion-bulbs. Abdominal distension was interpreted to be caused by chronic idiopathic intestinal pseudo-obstruction (CIIP), leading to protein-losing gastroenteropathy and hypalbuminemia caused by the CIIP. He died of DIC by myelodysplasic syndrome and DIC, two years later. Postmortem study demonstrated with severe loss of anterior horn cells and gliosis in the spinal cord. The Clarke's column was also affected. There was symmetrical degeneration in the dorsal column and corticospinal tracts. The cerebellum showed atrophy of molecular layer, prominent loss of Purkinje's cells and sparse granular cell layer, but no obvious change in the dentate nucleus. Neuronal loss in the dorsal root ganglia was remarkable. There were no alternations in the cerebral cortex, striatum, thalamus, subthalamic nucleus, and pontine nucleus, except for mild changes in substantia nigra and inferior olivary nucleus. This case was clinically suspected either of variant of Friedreich's ataxia or an early onset ataxia associated with hypoalbuminemia (EOAHA), although marked autonomic dysfunction was atypical. But the postmortem study, demonstrated with marked neuronal loss in anterior horn cells and cerebellan cortex and rather suggested an independent category of this case.

Friedreich Ataxia↗

[A case of visual perseveration attack caused by transverse-sigmoid sinus dural arteriovenous fistula].

A case of visual perseveration attack in the right superior quadrantic visual field caused by left transverse-sigmoid sinus dural arteriovenous fistula (AVF) was reported. A 75-year old right-handed man noticed that when he saw an object, the image sometimes persisted even after he looked away or the object was removed. The palinoptic images always appeared in the right superior quadrant visual field, consisted of a row of multiple objects all identical to the real one in shape, and were accompanied by photopsia. The palinoptic images disappeared within a few minutes. He was neurologically normal and showed no hemianopia or quadrantanopia on admission. EEG showed no epileptic discharge. CT scanning of the brain revealed a small high density area in the left occipital lobe. MRI demonstrated hyperintensity in the left inferior occipital lobe corresponding to the lower part of Brodmann's areas 18 and 19 on T2 weighted image and flow-voids caused by the dilated left occipital artery. 99mTc-ECD SPECT disclosed a decrease of regional cerebral blood flow in the left occipital lobe. Cerebral angiography revealed dural AVF fed by three branches of the left occipital artery and another branch of the left ascending pharyngeal artery with retrograde drainage into the left transverse sinus, sigmoid sinus, and dilated cortical veins. The left transverse and sigmoid sinuses were occluded. Visual perseveration disappeared following the treatment of the dural AVF by transarterial embolization. Because the lesions on MRI and SPECT improved after the treatment, these lesions were considered to represent not infarction but vasogenic edema due to venous congestion. We emphasized the role of the left inferior occipital lesion including the secondary visual cortex (Brodmann's areas 18 and 19) as the cause of visual perseveration in the right superior quadrantic visual field.

Aged↗

Expression of a bioactive bovine interleukin-12 using baculovirus.

Recombinant baculoviruses that express recombinant bovine interleukin-12 (rboIL-12) subunits, p35 and p40 subunits were constructed. A recombinant virus containing the p40 subunit gene expressed the p40 subunit as a 40kDa monomer and an 80kDa disulfide-linked homodimer in the infected insect cells and in the culture supernatant. The p35 subunit was expressed in a 30kDa monomer in the infected cells but not in the supernatant. Superinfection of both recombinant viruses into the cells in a spinner flask resulted in the formation of a 70kDa disulfide-bonded heterodimer detected in the supernatant by immunoblotting using anti-p40 and anti-p35 subunits antibodies. The superinfected culture supernatant showed induction of IFNgamma mRNA synthesis and IFNgamma production in bovine peripheral blood mononuclear cells. Thus, the bioactive rboIL-12 was produced in large scale using a baculovirus expression system.

Animals↗

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.

Journal Article↗

Possible involvement of cyclophilin B and caspase-activated deoxyribonuclease in the induction of chromosomal DNA degradation in TCR-stimulated thymocytes.

TCR engagement of immature CD4(+)CD8(+) thymocytes induces clonal maturation (positive selection) as well as clonal deletion (negative selection) in the thymus. However, the cell death execution events of thymocytes during the negative selection process remain obscure. Using a cell-free system, we identified two different DNase activities in the cytosol of in vivo anti-TCR-stimulated murine thymocytes: one that induced chromosomal DNA fragmentation, which was inhibited by an inhibitor of caspase-activated DNase, and another that induced plasmid DNA degradation, which was not inhibited by an inhibitor of caspase-activated DNase. We purified the protein to homogeneity that induced plasmid DNA degradation from the cytosol of anti-CD3-stimulated thymocytes and found that it is identical with cyclophilin B (Cyp B), which was reported to locate in endoplasmic reticulum. Ab against Cyp B specifically inhibited the DNA degradation activity in the cytosol of anti-CD3-stimulated thymocytes. Furthermore, recombinant Cyp B induced DNA degradation of naked nuclei, but did not induce internucleosomal DNA fragmentation. Finally, we demonstrated that TCR engagement of a murine T cell line (EL4) with anti-CD3/CD28 resulted in the release of Cyp B from the microsome fraction to the cytosol/nuclear fraction. Our data strongly suggest that both active caspase-activated DNase and Cyp B may participate in the induction of chromosomal DNA degradation during cell death execution of TCR-stimulated thymocytes.

Animals↗