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Biomedical subjects

A Ito

Publications and source records attributed to A Ito.

At least 73 records · Page 4Linked to original sources
PubMed2001

Aging of the zero-field-cooled magnetization in Ising spin glasses: experiment and numerical simulation.

Growth of the zero-field-cooled magnetization (ZFCM) under continuous heating with and without an intermittent stop(s) is studied on Ising spin glasses both experimentally and numerically. Despite the large difference between time scales of the experiment and the simulation, the ZFCM behavior observed in the two systems can be quantitatively interpreted by means of a common set of the scaling expressions based on the droplet picture. The results strongly suggest that the spin-glass coherence length reached by the laboratory time scales is about a hundred lattice spacings or less. Within this length scale no signature of the chaos effect (rejuvenation) has been found in the ZFCM measured.

Journal Article↗
PubMed2001

Triptolide, a novel diterpenoid triepoxide from Tripterygium wilfordii Hook. f., suppresses the production and gene expression of pro-matrix metalloproteinases 1 and 3 and augments those of tissue inhibitors of metalloproteinases 1 and 2 in human synovial fibroblasts.

OBJECTIVE: Various extracts of the Chinese herbal remedy Tripterygium wilfordii Hook. f. (TWHF) have been reported to be therapeutically efficacious in rheumatoid arthritis (RA) in China, but their mechanism of action remains unclear. We investigated the effect of triptolide, a diterpenoid triepoxide from TWHF, on the production of pro-matrix metalloproteinase 1 (proMMP-1; or procollagenase 1 or pro-interstitial collagenase 1), proMMP-3 (or prostromelysin 1), tissue inhibitors of metalloproteinases (TIMPs), and proinflammatory cytokines in human synovial fibroblasts and J774A.1 mouse macrophages. METHODS: Human synovial fibroblasts and mouse macrophages were cultured with interleukin-1alpha (IL-1alpha) or lipopolysaccharide (LPS) in the presence or absence of triptolide. The production of proMMPs 1 and 3, TIMPs 1 and 2, cyclooxygenase 1 (COX-1) and COX-2, prostaglandin E2 (PGE2), IL-1beta, and IL-6 was assayed by Western blot analysis and enzyme-linked immunosorbent assay. Gene expression of proMMPs 1 and 3, TIMPs 1 and 2, COX-1 and COX-2, IL-1alpha, IL-1beta, tumor necrosis factor alpha (TNFalpha), and IL-6 was also monitored by Northern blot analysis and reverse transcriptase-polymerase chain reaction. RESULTS: Triptolide suppressed the IL-1alpha-induced production of proMMPs 1 and 3 and decreased their messenger RNA levels in human synovial fibroblasts. In contrast, the IL-1alpha-induced gene expression and production of TIMPs 1 and 2 were further augmented by triptolide in the synovial cells. Triptolide also inhibited the IL-1alpha-induced production of PGE2 by selectively suppressing the gene expression and production of COX-2, but not those of COX-1. In addition, triptolide suppressed the LPS-induced production of PGE2 in mouse macrophages. Furthermore, the gene expression of IL-1alpha, IL-1beta, TNFalpha, and IL-6, as well as the production of IL-1beta and IL-6, were inhibited by triptolide in the LPS-treated mouse macrophages. CONCLUSION: We have demonstrated for the first time that the therapeutic effects of TWHF in RA are due in part to the novel chondroprotective effect of triptolide via the direct suppression of the production of proMMPs 1 and 3 and the simultaneous up-regulation of TIMPs in IL-1-treated synovial fibroblasts. Triptolide's interference with gene expression of proinflammatory cytokines and its known inhibitory effects on PGE2 production are also probably very effective.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2001

Augmentation of MHC class I antigen presentation via heat shock protein expression by hyperthermia.

Heat shock proteins are recognized as significant participants in immune reactions. In this study, we have demonstrated that the cell surface presentation of MHC class I antigen was increased in tandem with increased heat shock protein 70 (HSP70) expression and the immunogenicity of rat T-9 glioma cells was enhanced by hyperthermia. T-9 cells showed growth inhibition for 24 h after the heat treatment at 43 degrees C for 1 h in vitro, but then resumed a normal growth rate. HSP70 expression reached a maximum at 24 h after heating. Flow cytometric analysis revealed a significant increase in MHC class I antigen on the surface of the heated cells. The augmentation of MHC class I surface expression started 24 h after heating and reached a maximum 48 h after heating. The expression of other immunologic mediators, such as intracellular adhesion molecule-1 (ICAM-1) and MHC class II antigens, did not increase. In an in vivo experiment using immunocompetent syngeneic rats (F344), growth of the heated T-9 cells, with augmentation of MHC class I antigen surface expression, was significantly inhibited, while the cells grew progressively in nude rats (F344/N Jcl-rnu). Furthermore, compared with lymphocytes from non-immunized (PBS only injection) rats or rats injected with non-heated T-9 cells, the splenic lymphocytes of the rats in which the heated T-9 cells were injected displayed specific cytotoxicity against T-9 cells. These results suggest that HSP70 is an important modulator of tumor cell immunogenicity, and that hyperthermic treatment of tumor cells can induce the host antitumor immunity via the expression of HSP70. These results may benefit further efforts on developing novel cancer immunotherapies based on hyperthermia.

Animals↗
PubMed2001

Primary malignant fibrous histiocytoma of the ileum: report of a case.

We report herein a case of primary malignant fibrous histiocytoma (MFH) of the ileum. A 71-year-old Japanese man was admitted to our hospital with symptoms of abdominal pain and anorexia. Computed tomography, magnetic resonance imaging, a follow-through study of the small intestine, and angiography all demonstrated a tumor of the ileum suggestive of a primary malignancy. A partial resection of the ileum was performed. It was histopathologically and immunohistochemically diagnosed to be a storiform-type primary MFH of the ileum with peritoneal dissemination. There have been a total of 25 cases of primary small bowel MFH documented in the Japanese or Western literature including our case. The malignant potential of such tumors is high, and the prognosis tends to be very poor. Unfortunately, we could not conclude whether the poor outcome was due to a delayed diagnosis or instead to its biological malignant behavior, since the number of such reported cases is still too small to make any definitive conclusions.

Aged↗
PubMed2001

Increased expression of a nucleolar Nop5/Sik family member in metastatic melanoma cells: evidence for its role in nucleolar sizing and function.

F10 and BL6 cells of B16 mouse melanoma cells are metastatic after intravenous injection, but only BL6 cells can metastasize to lungs after subcutaneous injection. Differences in gene expression between the two cell lines were examined, and a greater expression of the Sik-similar protein (Sik-SP) gene was found in BL6 cells. Structurally, Sik-SP belongs to the nucleolar Nop5/Sik family whose members play central roles in ribosome biogenesis; however, the function of Sik-SP has not been examined. Cytology with green fluorescent protein-fused proteins showed that Sik-SP was localized to the nucleolus. To examine whether Sik-SP is involved in ribosome biogenesis, two parameters were measured: magnitude of ribosomal RNA synthesis per nucleus and magnitude of protein production from the same amount of mRNA of an exogenous luciferase gene. Both values and, in addition, nucleolar size were larger in COS-7 monkey kidney cells overexpressing Sik-SP and BL6 cells than in mock-transfected COS-7 and F10 cells, respectively. Sik-SP seemed to promote ribosome biogenesis in the nucleolus. Furthermore, the expression of Sik-SP seemed to confer a greater cell growth response to serum, because such a response was greater in BL6 cells and F10 cells overexpressing Sik-SP than in untreated and mock-transfected F10 cells. Sik-SP may render melanoma cells more competent to survive through augmenting the activity of nucleolus.

Animals↗
PubMed2001

Calcium phosphate clusters.

The potential energy surfaces associated with [Ca3(PO4)2n clusters are analyzed in detail using ab initio calculations for n ranging from one to four. Considering separated clusters, energy criteria favor the so-called Posner's cluster Ca9(PO4)6, which is the core of the actual structural model of amorphous calcium phosphate. This is rationalized through the existence of a distinct CaO bonding pattern in this cluster. Considering aggregated clusters as a possible model for amorphous calcium phosphate, the aggregation of Ca3(PO4)2 clusters appears as an alternative to Posner's hypothesis.

Biocompatible Materials↗
PubMed2001

Homogeneous epithelial gamma delta T cell repertoire of the skin is shaped through peripheral selection.

In contrast to the T cell receptor (TCR) diversity of major alpha beta T cells in lymphoid tissues, epithelial T cells of the murine skin, called dendritic epidermal T cells (DETC), express exclusively an invariant gamma delta TCR. Fetal thymic precursors of DETC immigrate to the skin before birth, and in adult mice T cells expressing the canonical gamma delta TCR identical to that of DETC are not found in other lymphoid or epithelial tissues. Here, we show that DETC precursors migrate to the gut as well as to the skin during fetal periods, but preferentially survive and expand in the skin after birth. We propose that similar to the thymic selection of the diverse alpha beta T cell repertoire, 'peripheral selection' of the homogeneous epithelial gamma delta T cell repertoire may be mediated by TCR signaling upon the recognition of the self-ligand, because the ligand for the DETC TCR was expressed only in the skin.

Animals↗
PubMed2001

Suppression by estrogen receptor beta of AP-1 mediated transactivation through estrogen receptor alpha.

The estrogen receptor (ER) is known to mediate gene transcription from AP-1 enhancer elements as well as the well-documented estrogen responsive elements (EREs). Investigations of AP-1 mediated transactivation through ER have been performed with rather complex promoters such as insulin like growth factor 1 (IGF-1) and collagenase promoters. In the present study, we investigated AP-1 mediated transactivation through ERalpha and ERbeta with a less complicated reporter consisting of only consensus AP-1 motifs. NIH 3T3 cells were transiently transfected with human ERalpha and ERbeta expression plasmids and AP-1-luc and ERE-luc reporters. 17beta-Estradiol failed to activate ERbeta-AP-1 responses while activating ERalpha-AP-1, ERalpha-ERE, ERbeta-ERE mediated transcription. On the other hand, antiestrogens such as tamoxifen enhanced AP-1 mediated transactivation through both ERalpha and ERbeta. An ERalpha positive human breast cancel cell line, MCF-7, also showed the same manner of AP-1 mediated transactivation through ERalpha. When NIH 3T3 with ERalpha and MCF-7 were co-transfected with ERbeta, E2 dependent AP-1 responses decreased in both cell lines depending on the amount of the ERbeta expression plasmid. These results suggest that ERalpha and ERbeta may function in opposition with ERbeta actually suppressing the function of ERalpha in AP-1 mediated transactivation.

3T3 Cells↗
PubMed2001

Neutral liposome-mediated delivery process of fluorescein-modified oligonucleotides in cultured human keratinocytes.

We propose a model of the intracellular delivery process in which fluorescein-labeled natural oligonucleotides (F-DNA) are transferred into the nuclei of cultured human keratinocytes. By encapsulation in neutral multilamellar lecithin liposomes, the F-DNA appeared to be protected against intracellular interactions with cellular materials and nuclease attacks in the cytoplasm during the process. The intracellular behavior of F-DNA and fluorescent phospholipid-labeled liposomes was observed by means of fluorescence analysis. Results showed that: F-DNA encapsulated in neutral multilamellar liposomes reached the cellular nuclei more efficiently than either free F-DNA, or F-DNA in unilamellar liposomes; the liposomal membranes appeared to be left in the cytoplasm. The reaction of F-DNA with complementary DNA was suggested by a rapid quenching of the fluorescence in the nucleus. In addition, the fluorescence decrease was evidently suppressed in the cytoplasm, indicating a protective effect of the neutral multilamellar liposomes against the interaction of F-DNA with cytoplasmic materials. The application of these findings to 'photo'-antisense studies has been discussed, where suppression of a gene expression is attempted by using oligonucleotide-attached fluorescein with the aid of a photo-induced covalent binding property.

Binding Sites↗
PubMed2001

Laboratory culture of the myxomycetes: formation of fruiting bodies of Didymium bahiense and its plasmodial production of Makaluvamine A.

Laboratory cultures of more than 100 strains of myxomycetes were investigated, and the spore germinations of six strains were observed. The plasmodium of the myxomycete Didymium bahiense was cultured on oatmeal agar plates in a laboratory. The formation of fruiting bodies was observed in a plate culture. From the cultured organisms, a marine sponge metabolite, makaluvamine A (1), was isolated and identified on the basis of spectral data.

Animals↗
PubMed2001

Cytotoxic polyacetylenes from the twigs of Ochanostachys amentacea.

Bioassay-guided investigation of the twigs of Ochanostachys amentacea using LNCaP (hormone-dependent human prostate cancer) cells as a monitor led to the isolation of three alkynes, the known (S)-17-hydroxy-9,11,13,15-octadecatetraynoic acid (minquartynoic acid, 1) and two novel analogues, (S)-17,18-dihydroxy-9,11,13,15-octadecatetraynoic acid (2) and (S)-17-hydroxy-15E-octadecen-9,11,13-triynoic acid (3). Compounds 1-3 were tested against a panel of human tumor cell lines and found to be significantly cytotoxic.

Alkynes↗
PubMed2001

Monoclonal antibody (5F3) defining renal cell carcinoma-associated antigen disialosyl globopentaosylceramide (V3NeuAcIV6NeuAcGb5), and distribution pattern of the antigen in tumor and normal tissues.

Renal cell carcinoma (RCC) has been characterized by high expression of three types of disialogangliosides: two based on lacto-series type 1 structure (disialosyl Lc(4), GalNAc disialosyl Lc(4)), the other based on globo-series structure (disialosyl globopentaosylceramide; disialosyl Gb5). The present study established a mAb, 5F3, directed to disialosyl Gb5. 5F3 was established after immunization with RCC cell line ACHN. The major disialoganglioside antigen isolated from ACHN cells, showing specific reactivity with 5F3, was characterized unequivocally as disialosyl Gb5 (V(3)NeuAcIV(6)NeuAcGb5) by identification of the core structure as globopentaosylceramide (Gb5) after enzymatic and acid hydrolysis, and by 2-dimensional (1)H-NMR spectroscopy. 5F3 does not react with monosialosyl Gb5 (V(3)NeuAcGb5), Gb5, or any lacto-series structures. 5F3 strongly stained 19 of 41 cases of primary RCC tissue. It reacted with proximal tubules (but not distal tubules) of kidney, microglial cells of cerebrum and cerebellum, goblet cells of stomach and intestine, smooth muscle of various organs. It did not react with parenchymatous cells of various organs, except for kidney epithelia and prostate stroma. Immunostaining of RCC tissue by mAb 5F3, in combination with staining by other antibodies directed to globo-series and lacto-series structures, has prognostic significance in defining metastatic potential of RCC.

Antibodies, Monoclonal↗
PubMed2001

Heat-inducible TNF-alpha gene therapy combined with hyperthermia using magnetic nanoparticles as a novel tumor-targeted therapy.

Heat-induced therapeutic gene expression is highly desired for gene therapy to minimize side effects. Furthermore, if the gene expression is triggered by heat stress, combined therapeutic effects of hyperthermia and gene therapy may be possible. We combined TNF-alpha gene therapy driven by the stress-inducible promoter, gadd 153, with hyperthermia using magnetite cationic liposomes (MCLs). In nude mice, MCLs induced cell death throughout much of the tumor area on heating under an alternating magnetic field. This heat stress also resulted in a 3-fold increase in TNF-alpha gene expression driven by the gadd 153 promoter as compared with that of nonheated tumor. TNF-alpha gene expression was also observed in the peripheral area where the hyperthermic effect was not enough to cause cell death. The combined treatment strongly arrested tumor growth in nude mice over a 30-day period, suggesting potential for cancer treatment.

Animals↗
PubMed2001

Epidermal growth factor and 1alpha,25-dihydroxyvitamin D3 suppress lipogenesis in hamster sebaceous gland cells in vitro.

We have previously reported the establishment of a culture system of hamster auricular sebocytes. Although their morphologic and biochemical properties are very similar to those of human sebocytes, the regulation of lipogenesis is not clear. Therefore, we investigated the effect of epidermal growth factor, all-trans retinoic acid, 1alpha,25-dihydroxyvitamin D3, and androgens such as testosterone and 5alpha-dihydrotestosterone on lipogenesis in cultured hamster sebocytes. Intracellular lipid droplets detected with Oil-Red-O staining were observed in 5 d cultures and increased in a time-dependent manner; 40.7% +/- 1.11% of 2 wk cultured cells tested lipid-positive by flow cytometric analysis. When the hamster sebocytes were cultured in the presence of epidermal growth factor, all-trans retinoic acid, or 1alpha,25-dihydroxyvitamin D3, the intracellular lipid droplets were diminished by all-trans retinoic acid and epidermal growth factor, and slightly by 1alpha,25-dihydroxyvitamin D3. The intracellular lipid droplets consisted mainly of triglycerides (71.8%) and, as minor components, cholesterol (18.0%), wax esters (3.6%), and free fatty acids (6.6%). Epidermal growth factor and all-trans retinoic acid decreased the intracellular accumulation of triglycerides (92.6% and 96.1% inhibition, respectively) and free fatty acids (54.3% and 62.6% inhibition, respectively) in the sebocytes. In addition, 1alpha,25-dihydroxyvitamin D3 decreased the triglyceride level (34.3% inhibition), but augmented the accumulation of wax esters (30% increase). There was no difference in the level of cholesterol as a result of these treatments, however. In contrast, 5alpha-dihydrotestosterone augmented the formation of intracellular lipid droplets along with an increase in the accumulation of triglycerides in hamster sebocytes. Our findings that regulation of lipogenesis by all-trans retinoic acid and androgen in hamster sebocytes is identical to regulation in humans suggest that hamster sebocytes are useful for the elucidation of sebaceous function at the cellular level. Furthermore, this is the first evidence that epidermal growth factor and 1alpha,25-dihydroxyvitamin D3 may act as suppressors in the regulation of lipogenesis in hamster sebocytes in vitro.

Animals↗
PubMed2001

Dystrophic scrotal calcinosis originating from benign eccrine epithelial cysts.

Scrotal calcinosis has been classified as a form of idiopathic calcinosis cutis. However, the pathogenesis of the calcified nodules has not been fully elucidated: it is still unclear whether the condition is truly idiopathic, or the result of breakdown of calcified epithelial cysts. We describe a 29-year-old Japanese patient with scrotal calcinosis originating from epithelial cysts. Light microscopy revealed a large epithelial cyst containing von Kossa-positive material and several small dilated ductal structures beside the cyst. The epithelia of the cyst and ductal structures were connected, showing similar eccrine duct differentiation on immunohistochemical staining and electron microscopy. In the cyst lumen, calcium was present as needle-shaped crystals. The pathogenetic mechanism of calcium deposition seemed to be due to excessive production and discharge of matrical debris and sulphated mucopolysaccharides, which derived from luminal cells, and their accumulation in the lumina.

Adult↗
PubMed2001

Generation of hepatitis C virus-specific cytotoxic T lymphocytes from healthy individuals with peptide-pulsed dendritic cells.

BACKGROUND AND AIMS: In hepatitis C virus (HCV) infection, cytotoxic T lymphocytes (CTL) are involved in liver inflammation and contribute to the reduction of viral load. Antibodies for HCV-CTL precursor frequencies (CTLpf) are relatively low in chronic hepatitis C, and this may be related to the poor CTL response in vivo. The aim of this study was to assess the efficacy of dendritic cells (DC) as antigen-presenting cells in CTL generation from low CTLpf. METHODS: To confirm the rationale of using DC to prime naive T cells, five HCV-uninfected individuals were enrolled in the study. We obtained DC by maturation from peripheral progenitors under stimulation with granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-4 and IL-1alpha. Autologous T cells were cultured with DC or concanavalin-A-induced blasts loaded with four HCV-derived peptides bearing human leukocyte antigen (HLA)-A*0201 or -A24 motifs for 28 days under IL-7 and IL-2 stimulation. The lytic activity against peptide-pulsed targets was assessed by using a [51Cr]-releasing assay. RESULTS: The DC strongly expressed HLA class I, II, B7-1 and B7-2, but not phenotypic markers of T-, B-, natural killer (NK)-cells or monocytes. The CD8-positive, HLA-class I-restricted and HCV peptide-specific CTL were generated with DC from HLA-A antigen-matched subjects, whereas no CTL activity was detected with concavalin (Con-A) blasts. We were thus able to generate HCV specific CTL from naive precursors with peptide-pulsed DC. CONCLUSIONS: This DC-based system can be used to generate CTL of desired antigen specificity, even from a source with low CTLpf.

Adult↗