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Biomedical subjects

H Ueki

Publications and source records attributed to H Ueki.

At least 73 records · Page 4Linked to original sources

Role of cytokines in controlling connective tissue gene expression.

Recently, the role of cytokines in controlling gene expression of connective tissue components has been increasingly emphasized. Many cytokines have been shown to have specific effects on gene expression of connective tissue components, and the roles of cytokines in controlling connective tissue metabolism during wound healing and in fibrosis have increasingly been discussed. In this article, the effects of cytokines on regulation of gene expression of connective tissue components, especially of type I collagen were described. We analysed transcriptional control of the alpha 1(I) collagen gene by TNF-alpha by means of DNA mediated transfection experiments using recombinant plasmids in which the promoter region of the human alpha 1(I) collagen had been fused to the chloramphenicol acetyl-transferase (CAT) gene, in human dermal fibroblasts. It was found that TNF-alpha reduced alpha 1(I) collagen transcription through at least up to -107 bp upstream of the human alpha 1(I) collagen promoter gene in dermal fibroblasts.

Animals↗

[Köbner phenomenon in lupus erythematosus].

In several cases of lupus erythematosus (SLE, SCLE, DLE), the Koebner phenomenon could be seen in the apparently normal skin of patients following traumas, scratching effects, operation scars, contact dermatitis, pressure from sock tops, application of liquid nitrogen, exposure to strong sun light, etc. The interval between exposure to such provocation factors and appearance of the isomorphic reactions varied from case to case. In SLE patients receiving systemic treatment with glucocorticosteroids, the Koebner phenomenon could not be found, while it was detected in patients with generalized DLE who had never received any systemic glucocorticoid hormones. It was not seen in patients with localized DLE. There was no direct relationship between the appearance of humoral autoantibodies and onset of the Koebner phenomenon. With regard to the histopathogenesis of the Koebner phenomenon, it is thought that disturbances of the local cellular repair processes and of the cytokine network, with expression of adhesion molecules, might be involved. The Koebner phenomenon may be a valuable model for the investigation of lupus erythematosus.

Adult↗

Spectral analysis of intraluminal pressure in the anastomosed ileal segment of the rat in vitro.

Spectral analysis of the spontaneous intraluminal pressure of the isolated ileal segments in vitro was performed (1) before transection and soon after union (acute model) and (2) until 67 days after anastomosis (chronic model). A single peak was found in the spectral arrays of the acute model before transection. However, more than two peaks were clearly found in spectral arrays of both acutely or chronically anastomosed models. Motor activities of both oral and anal part of the anastomosis seem to be reflected in the spectral analysis of the intraluminal pressure of the isolated segments in vitro. More than two peaks in spectral arrays suggest that the synchronized and coordinated motor activity was not recovered, at least, until 67 days after anastomosis.

Anastomosis, Surgical↗

Effects of tretinoin tocoferil on gene expression of the extracellular matrix components in human dermal fibroblasts in vitro.

Recently, it has been reported that tretinoin tocoferil (TT), a synthesized ester-bond compound of all-trans-retinoic acid and alpha-tocopherol, accelerates the formation of granuloma and is effective in promoting experimental open skin wound healing. To investigate whether TT affects the gene expression of extracellular matrix components of human dermal fibroblasts, we measured the mRNA levels of various extracellular matrix components of fibroblasts incubated with TT using specific cDNA probes. The mRNA levels of elastin increased up to 30% of the controls and those of collagen III and VI up to 60%. The mRNA levels of collagen I and fibronectin remarkably increased up to 90% of the controls. These results suggest that the stimulatory effect of TT on the gene expression of many extracellular matrix components might be one of the mechanisms of its promotion of wound healing.

Actins↗

Decreased CD4+CD45RA+ lymphocytes in peripheral blood of systemic lupus erythematosus can recover after separation from patient's sera.

Decrease in CD4+CD45RA+ lymphocytes in peripheral blood of systemic lupus erythematosus (SLE) patients has been reported. In this study, mononuclear cells were separated from peripheral blood of SLE patients, and the CD4+CD45RA+ cells were counted by flow cytometry just after separation and also 1 week after incubation in vitro. Furthermore, healthy lymphocytes were incubated with SLE patient's sera, and the Ca2+ level was measured to investigate the interaction of patient's sera with healthy lymphocytes. The CD4+CD45RA+ lymphocytes were found to be decreased in number on the first day just after separation of lymphocytes, but recovered to normal levels after 1 week culture without patient's sera. The intracellular Ca2+ level in normal lymphocytes increased 1 min after incubation with patient's sera, but not with healthy control sera. These results suggest that CD4+CD45RA+ cells are persistently activated in the peripheral blood of SLE patients, and that their sera contain some extrinsic factors which could activate the lymphocytes.

Adult↗

Activation of fibroblast proliferation by Werner's syndrome fibroblast-conditioned medium.

The effects of Werner's syndrome (WS) fibroblast-conditioned medium on cell proliferation and collagen production of normal fibroblasts were studied using four WS fibroblast strains. The conditioned medium from the WS fibroblasts brought about activation of normal fibroblast proliferation, whereas, that from late passage normal fibroblasts and fibroblasts from aged donors' skin did not. Collagen and non-collagenous protein synthesis in normal fibroblasts were increased by the addition of conditioned medium from the WS fibroblasts, but the relative rates of collagen synthesis and non-collagenous protein synthesis were unaltered. These results suggest that activation of fibroblast proliferation by conditioned medium is one of the characteristics of WS fibroblasts.

Adult↗

Decreased collagenase expression in cultured systemic sclerosis fibroblasts.

One cause of the excessive deposition of collagen in systemic sclerosis is thought to be abnormal functioning of fibroblasts. The purpose of this study is to determine whether there is decreased expression of collagenase in systemic sclerosis fibroblasts. In this study, we analyzed collagen and collagenase expression in dermal fibroblasts derived from eight patients with systemic sclerosis and compared the findings with those from nine sex- and age-matched healthy subjects. Increased collagen synthesis accompanying enhanced mRNA levels was observed in two of eight strains, whereas all eight strains showed remarkable decreases in collagenase activity and production. There were no differences in the levels of collagenase mRNA between the systemic sclerosis strains and the normal strains. Results suggest that decreased collagenase expression is a characteristic of systemic sclerosis fibroblasts, and both increased collagen expression and decreased collagenase expression in systemic sclerosis fibroblasts may result in the excessive accumulation of collagen in patients with systemic sclerosis. It is also suggested that decreased collagenase expression is altered at translational and/or post-translational levels.

Adult↗

Significance of tubuloreticular structures forming in Daudi cells cultured with sera from mothers bearing infants with neonatal lupus erythematosus.

It is known that infants with neonatal lupus erythematosus (NLE) may be born to mothers whose sera are positive for the anti-Ro/SSA antibody. However, women who have this antibody do not always give birth to children with NLE. We have demonstrated tubuloreticular structures in vascular endothelial cells in the skin lesions of infants with NLE. Tubuloreticular structures could no longer be detected at the site of the lesions once the annular erythema had resolved, and the anti-Ro/SSA antibody test had become negative. The probability of a child being born with NLE was assessed by observing whether tubuloreticular structures were formed in Daudi cells cultured with sera from eight mothers who were anti-Ro/SSA antibody positive. Tubuloreticular structures formed in Daudi cells cultured with sera from four mothers who bore infants with NLE, but not in Daudi cells cultured with sera from four other mothers who bore normal infants. These results suggest that women who are positive for the anti-Ro/SSA antibody have a higher risk of bearing infants with NLE if tubuloreticular structures are formed in Daudi cells cultured with sera from these women, whereas this risk is lower if tubuloreticular structures do not develop in Daudi cells.

Adult↗

Stimulatory release of hepatic lipase activity from cultured rat hepatocytes by sodium orthovanadate: rapid increase in cyclic adenosine monophosphate content.

The release of hepatic triacylglyceride lipase [EC 3.1.1.3] has been examined in isolated hepatocytes in primary culture. The stimulatory release of activity from the hepatocytes into the medium by sodium orthovanadate (vanadate) was observed in a time- and dose-dependent manner. However, insulin failed to have this stimulatory action. Moreover, vanadate rapidly increased the cyclic adenosine monophosphate (cyclic AMP) content in hepatocytes in a time- and dose-dependent manner. The treatment of hepatocytes with H-89, which is a potent cyclic AMP-dependent protein kinase inhibitor, decreased the stimulatory release of hepatic lipase activity by vanadate. The vanadate-stimulated release of the enzyme activity was suppressed by uncouplers. In addition, the incorporation of [3H]leucine into protein was increased in the presence of vanadate. Under the marked inhibition of protein synthesis by cycloheximide, vanadate still showed a full effect on the release of the enzyme activity. These results suggest that the vanadate-stimulated release of hepatic lipase activity from the cultured hepatocytes is associated with a rapid increase in intracellular cyclic AMP content, probably due to an activation of cyclic AMP-dependent protein kinase which requires a metabolic energy process rather than an elevation in enzyme molecule synthesis.

Animals↗

Stimulatory release of lipoprotein lipase activity with activation of protein tyrosine kinase produced by low molecular weight dextran sulfate in Ehrlich ascites tumor cells.

Lipoprotein lipase (LPL), which is responsible for the hydrolysis of lipoprotein triacylglyceride, has been examined in Ehrlich ascites tumor cells. Low molecular weight dextran sulfate (DXS, M.W. 3.2 kDa) stimulates the release of the enzyme activity from the tumor cells into the incubation medium in a time-dependent manner. The stimulatory effect of DXS was markedly decreased by incubation with protein tyrosine kinase (TK) inhibitors, such as ST 638, biochanin A and amiloride. The activity of the partially purified TK preparation from the tumor cells was found to be increased following incubation with DXS in a manner which was both time- and dose-dependent. These results suggest that the stimulatory release of LPL activity by DXS is associated with the activation of TK in the tumor cells.

Animals↗

Polyclonal human T-cell activation by silicate in vitro.

Silica (SiO2) or related substances such as silicone ([-R2Si-O-]n), which is used in plastic surgery, or asbestos (e.g. chrysotile; 3MgO.2SiO2.H2O) have 'adjuvant effects'. In a study of scleroderma patients in Germany more than 78% had experienced exposure to silicate dust. T-cell receptor (TcR) V beta gene analysis on CD4- CD8- double-negative alpha beta T cells from scleroderma patients, using polymerase chain reaction (PCR), showed that certain V beta genes, V beta 5, V beta 7 and V beta 17, were predominantly expressed in the cells. We found that certain V beta repertoires, V beta 5.3 and V beta 6.7, were predominantly expressed on fractionated T cells with a high Ca2+ level that had been stimulated by chrysotile in vitro. The intracellular Ca2+ level in human peripheral blood mononuclear cells (PBMC) increased after incubation with silica or chrysotile. Interleukin-2 (IL-2) release from PMBC also rose significantly with chrysotile stimulation, but no change was observed when major histocompatibility complex (MHC) class II DP/DR positive cells were depleted. Therefore, our results support the possibility that silicate acts as a superantigen.

Adult↗

[Psychological test as a mass-screening system for depression].

A mass-screening system for depression is aimed at calculation of the prevalence rate, or at mental health checks in employees. But with the recent increased interest in mental health and QOL, depression has become an important issue at every stage of the life cycle. In this paper, we review psychological screening tests for child, adult and aged from the viewpoint of life cycle. Some tests, especially for children and the aged need further tests regarding reliability and validity. What is clarified and which approach in mental health is indicated by the screening test must be further examined. Further development of screening tests, appropriate to each life cycle, is needed.

Depression↗

Effects of tumor necrosis factor-alpha on connective tissue metabolism in normal and scleroderma fibroblast cultures.

Recent studies have demonstrated that tumor necrosis factor-alpha (TNF-alpha) selectively decreases production of collagens I and III, the major types of collagen in the dermis, and increases production of collagenase in cultured dermal fibroblasts. The effects of TNF-alpha on collagens I, III and VI, fibronectin and collagenase gene expression by fibroblasts derived from normal individuals and patients with systemic sclerosis (SSc) were studied. SSc is characterized by excessive accumulation of collagen in the skin and in certain organs. TNF-alpha inhibited collagen production and mRNA levels of collagens I and III and of fibronectin, and stimulated collagenase activity and collagenase mRNA levels in SSs fibroblasts. Levels of mRNA for alpha 1 (VI) and alpha 3 (VI) collagen and for beta-actin were unaltered in SSc fibroblasts incubated with TNF-alpha. Similar results were observed for mRNA levels in normal fibroblasts incubated with TNF-alpha. These results suggest that TNF-alpha could be expected to be beneficial in the treatment of SSc. In addition, our results indicated that collagen-VI expression is regulated independently from expression of collagens I and III, and expression of fibronectin and collagens I and III are regulated in parallel in fibroblasts treated with TNF-alpha.

Adult↗

Decreased type VI collagen gene expression in cultured Werner's syndrome fibroblasts.

Gene expression of collagens VI, I, and III in Werner's syndrome was studied by measuring messenger RNA (mRNA) and protein production levels in four fibroblast strains from patients with Werner's syndrome and comparing them with age-matched healthy subjects. Levels of type VI collagen mRNA were decreased in all Werner's syndrome fibroblast strains and the decreases were in parallel in all three chains (alpha 1, alpha 2, and alpha 3) of type VI collagen. A coordinate increase of the alpha 1(I) and alpha 1(III) collagen mRNA levels was observed in three of the four Werner's syndrome fibroblast strains. However, no qualitative abnormality of these mRNA transcripts in Werner's syndrome fibroblasts were found by Northern blot analysis. Changes in type VI and type I collagen mRNA correlated well with production levels of corresponding proteins, as determined by immunologic assays. These data suggest that there are changes in expression of multiple connective tissue constituents in Werner's syndrome fibroblasts.

Adult↗

Small round and spindle cell sarcoma with neuronal differentiation and oncocyte-like features of the thoracic wall: a case report with histological, immunohistochemical and ultrastructural examinations.

A case of small round and spindle cell sarcoma with neuronal differentiation and oncocyte-like features is presented. The tumor was encountered in a 32 year old Japanese woman with an initial presentation of palpable tumor in the left lateral region of the thorax. The resected tumor was a partially well encapsulated whitish medullary one and consisted of small round and spindle tumor cells, together with so-called rhabdoid cells in the small round cell area. Although pseudorosettes were often observed, true rosette formation could not be detected anywhere. Ultrastructurally, despite a histologic variety of tumor cells, most tumor cells possessed numerous mitochondria, some of which occasionally contained abnormal filamentous or crystalloid structures. Various amounts of microfilaments were present in most tumor cells and microtubules were present in a few. A minority of small round cells possessed a small number of neurosecretory granules, especially in short cytoplasmic processes. A positive immunoreaction for neuron specific enolase was found by immunohistochemical examination in several small round tumor cells and for neurofilaments in lesser numbers. Despite the lack of S-100 protein, MB2 was detected in both small round and spindle cells. On the basis of these findings, the tumor of the present case corresponds to malignant peripheral nerve sheath tumor with neuronal differentiation and oncocytic features.

Adult↗

Stimulatory release of hepatic lipase activity from liver by epidermal growth factor.

We have found that release of hepatic lipase activity is stimulated from liver slices by epidermal growth factor (EGF) into the medium in a time-dependent manner. This novel effect of EGF was markedly decreased by various tyrosine kinase inhibitors, such as alpha-cyano-3-ethoxy-4-hydroxy-5-phenyl-thiomethyl cinnamamide, amiloride and biochanin A. The stimulation by EGF was also suppressed, however, by dibutyryl cyclic adenosine monophosphate, and 3-isobutyl-1-methylxanthine, a cyclic nucleotide dependent phosphodiesterase inhibitor. These findings show that the stimulatory release of the enzyme activity by EGF is associated with the activation of tyrosine kinase activity and with the intracellular cyclic adenosine monophosphate level.

1-Methyl-3-isobutylxanthine↗

Increase in lipoprotein lipase activity in isolated rat adipose tissue by selenate.

Sodium selenate (selenate), as well as insulin, increased the lipoprotein lipase (LPL) activity in isolated rat fat pads in a time- and dose-dependent manner. The increase effect of selenate was not additive to that of insulin. The action of selenate and insulin was decreased by amiloride and disappeared when Ca2+ was omitted from the incubation medium. Loading of a chelator of intracellular Ca2+ to the fat pads also greatly inhibited the action of selenate. The maximal increase in inositol 1,4,5-trisphosphate (IP3) content was observed with a 30-s incubation of the fat pads with selenate. Dibutyryl cyclic AMP, 3-isobutyl-1-methylxanthine, carbonyl cyanide m-chlorophenylhydrazone, tunicamycin, and monensin all inhibited the increase effect of selenate on the LPL activity to various extents. These results suggest that selenate increases the LPL activity via amiloride- and monensin-sensitive processes, involving the Ca2+ mobilization linked to a rapid increase in the IP3 content in fat pads.

1-Methyl-3-isobutylxanthine↗

Analysis of collagen gene expression by cultured fibroblasts in morphoea.

Collagen gene expression was studied in dermal fibroblasts derived from the inflammatory and sclerotic skin lesions of patients with localized or generalized morphoea. The levels of mRNA for type I collagen in early-passage fibroblasts derived from inflammatory lesions were higher than those obtained from the uninvolved skin, whereas those fibroblasts obtained from sclerotic lesions were unaltered. No alteration in type I collagen mRNA levels was observed in late-passage fibroblasts derived from the inflammatory lesions. The relative rate of collagen to total protein synthesis in early-passage fibroblasts derived from inflammatory lesions was higher than that of fibroblasts from uninvolved skin, while no alteration or a slight decrease was observed in fibroblasts from the sclerotic lesions. The data suggest that the inflammatory reactions induce increased collagen synthesis by fibroblasts in the skin in scleroderma.

Actins↗