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Biomedical subjects

T Shimauchi

Publications and source records attributed to T Shimauchi.

At least 19 recordsLinked to original sources
PubMed2007

Innate immunity mediated by epidermal keratinocytes promotes acquired immunity involving Langerhans cells and T cells in the skin.

Skin is an immunological organ consisting of epidermal cells, i.e. keratinocytes and Langerhans cells (LCs, antigen-presenting dendritic cells), and both innate and acquired immune systems operate upon exposure of the skin to various external microbes or their elements. To explore the relationship between innate and acquired immunities in the skin, we investigated whether Toll-like receptor (TLR) ligation of epidermal cells enhances the ability of LCs to present a specific antigen to T cells in mice. LC-containing epidermal cells were incubated with CpG oligonucleotide (TLR9 ligand) modified with trinitrophenyl hapten, and cultured with hapten-primed CD4(+) T cells. TLR9 ligand was capable of enhancing the hapten-presenting ability of LCs when LC-enriched epidermal cells, but not purified LCs, were used as the LC source, suggesting that bystander keratinocytes play a role in the enhancement of LC function. Cultivation of freshly isolated epidermal cells with CpG promoted the expression of major histocompatibility complex (MHC) class II and CD86 molecules on LCs. CpG enhanced the production of interleukin (IL)-1alpha, granulocyte-macrophage colony-stimulating factor (GM-CSF) and tumour necrosis factor (TNF)-alpha by primarily cultured keratinocytes. The addition of a cocktail of neutralizing antibodies against these cytokines abrogated the CpG-promoted, antigen-presenting ability of LC-enriched epidermal cells. Moreover, the addition of culture supernatants from CpG-stimulated keratinocytes restored the ability of purified LCs. Our study demonstrated that although the direct effect of CpG on LCs is minimal, LC function can be up-regulated indirectly by cytokines released by CpG-stimulated keratinocytes. This also implies that innate immunity evoked by TLR ligation of keratinocytes enhances acquired immunity comprising LCs and T cells.

Animals↗
PubMed2005

Purpuric adult T-cell leukaemia/lymphoma: expansion of unusual CD4/CD8 double-negative malignant T cells expressing CCR4 but bearing the cytotoxic molecule granzyme B.

A 78-year-old Japanese woman with adult T-cell leukaemia/lymphoma (ATL) presented with an unusual purpuric and erythematous eruption on the face and trunk. Immunohistochemical and flow cytometric analyses showed that the tumour cells were CD4/CD8 double-negative, and expressed CCR4 T-helper (Th) 2 chemokine receptors. Despite these features, the cells aberrantly produced granzyme B, which is a cytotoxic molecule usually produced by CD8(+) cytotoxic T cells, natural killer cells, or occasionally by Th1 cells. In a purpuric lesion, extravasation of erythrocytes was associated with an infiltrate of these cytotoxic tumour cells. Our case suggests phenotypical and functional heterogeneity of tumour cells in ATL, which may be closely related to the clinical appearance of the skin eruption.

Aged↗
PubMed2004

Evidence for polyclonal infection of Epstein-Barr virus in a patient with primary cutaneous anaplastic large cell lymphoma.

We report a case of CD30 + primary cutaneous anaplastic large cell lymphoma. The lymphoma cells were shown to express the Epstein-Barr virus (EBV)-encoded small RNAs by in situ hybridization and to have EBV genomes by PCR, whereas no monoclonal band was detected by Southern blot analysis using the EBV terminal repeat probe. These data suggested polyclonal infection by EBV, which provides evidence that EBV plays little part in the pathogenesis of this tumour even in the infected cases.

Aged↗
PubMed2003

Differential response to low temperature of two Delta6 fatty acid desaturases from Mucor circinelloides.

A recently identified Delta6 fatty acid desaturase in Mucor rouxii shows a low sequence homology (approximately 24% at the amino acid level) to that isolated from Mortierella alpina, but is phylogenetically closer to a plant enzyme, suggesting the occurrence of Delta6 desaturase isozymes in Mucorales molds. In the present study, two types of Delta6 desaturases, mcD6-1 ( Mo. alpina type) and mcD6-2 ( M. rouxii type), were cloned from Mucor circinelloides. When the cloned genes were expressed in the yeast Saccharomyces cerevisiae in the presence of a linoleic acid substrate (C18:2Delta9, 12), a newly generated gamma-linolenic acid (C18:3Delta6, 9, 12) was detected in the cells, which confirmed the suspected enzymatic function of the recombinant protein. This is the first report of Delta6 desaturase isozymes present in one organism. Northern analysis demonstrated that the amount of mcD6-2 mRNA was less than half of that of mcD6-1 mRNA in cells grown at 28 degrees C. However, upon cultivation of the cells at 15 degrees C for 0.5-1 h, mcD6-2 mRNA rapidly increased by up to 1.5-fold and then gradually decreased. By contrast, mcD6-1 transcripts levels did not fluctuate significantly for 1 h after the temperature shift, but declined by 75% over the next 2 h. The gamma-linolenic acid content in total fatty acid from M. circinelloides decreased at 28 degrees C, but was maintained at approximately 30% at 15 degrees C. These data suggest that Delta6 desaturase isozymes play physiologically distinct roles in the maintenance of cellular lipids and adaptation to low temperature.

Amino Acid Sequence↗
PubMed2000

[A case of squamous cell carcinoma that developed on chronic tar dermatosis].

A 79-year-old Japanese man visited our clinic for evaluation of a large tumor on the left wrist and multiple keratotic tumors. He had handled creosote oil, which is a purified product of coal tar production, for 50 years. Physical examinations revealed poikiloderma with multiple hyperkeratotic tumors on the back of his hand and forearm bilaterally, and a cauliflower-like tumor, 80 x 60 x 15 mm in size, on the left wrist. Histopathologically, the large tumor showed a proliferation of atypical squamoid cells with many keratinization foci, indicating well-differentiated squamous cell carcinoma.

Aged↗
PubMed1989

Promotion of calcification by imidazole and its suppression by diltiazem in the growth cartilage of rats with HEBP induced rickets.

The object of our experiments was to determine the effect of imidazole on the growth cartilage of rats with HEBP induced rickets. When HEBP (1-hydroxyethylidene-1, 1-bisphophonic acid) was given to young rats in large doses over a short period, rickets was consistently produced. We found that imidazole had a calcification promoting action in the growth plate cartilage where there had been an increase in thickness due to the inhibition of calcification. In an attempt to clarify the mechanism of accelerated calcification due to imidazole, the effects of diltiazem, a calcium antagonist, were observed; it was found to suppress the accelerated calcification. If diltiazem inhibits the entry of calcium ions into the cells of the growth cartilage, as it does in smooth muscle and myocardial cells, then our results indicate that intracellular concentrations of calcium may play an important role in the accelerated calcification due to imidazole.

Animals↗
PubMed1989

The tumor cells (FA-6) established from a pancreatic cancer associated with humoral hypercalcemia of malignancy: a simultaneous production of parathyroid hormone-like activity and transforming growth factor activity.

Human pancreatic cancer cells (FA-6) producing bone resorbing factor were established in culture. A biopsied lymphnode from a patient with pancreatic cancer associated with humoral hypercalcemia of malignancy (HHM) was transplanted to nude mice, and the cells producing high parathyroid hormone (PTH)-like activity were selected by a limited dilution from outgrowth of the xenografts of the tumor grown in nude mice. The conditioned media contained an activity to stimulate the resorption of mouse calvaria in vitro which was indomethacin-insensitive. The conditioned media had both alpha-type and beta-type transforming growth factor (TGF) activity but no interleukin-1 activity. TGF-alpha activity was co-eluted with PTH-like activity from gel-chromatography at around 15 kDa. The FA-6 cells now established are the first cells of pancreatic cancer associated with HHM producing both PTH-like and TGF-alpha activities along with bone resorbing activity.

Animals↗
PubMed1987

A comparative study of the calcification-promoting action of 1,25 (OH)2D3 and calcitonin on the growth cartilage of rats with 1-hydroxyethylidene-1, 1-biphosphonic acid (HEBP)-induced rickets.

When HEBP (1-hydroxyethylidene-1, 1-biphosphonic acid) was administered to young rats in large doses over a short period rickets was consistently produced. When HEBP was administered concomitantly with 1,25 (OH)2D3 or calcitonin (CT), calcification appeared in the growth-plate cartilage where there had been an increase in thickness due to the inhibition of calcification. This experiment was done in an attempt to clarify differences in the calcification-promoting mechanisms of 1,25 (OH)2D3 and CT. The serum alkaline phosphatase level was reduced in rats with an accelerated calcification following the administration of 1,25 (OH)2D3, but there was no reduction in the serum alkaline phosphatase level in rats in which the calcification was accelerated by the administration of CT. The mode of appearance of calcification in the growth-plate cartilage by 1,25 (OH)2D3 or CT differed, depending on the time of administration. These results suggest that mechanisms involved in the enhancement of calcification by 1,25 (OH)2D3 and CT differ in cases where rickets are induced by HEBP.

Alkaline Phosphatase↗
PubMed1986

Cloning and sequencing of the PHO80 gene and CEN15 of Saccharomyces cerevisiae.

The PHO80 gene, which is one of the regulatory genes exerting negative control in the pho system of Saccharomyces cerevisiae, was cloned. The 1.8 kb DNA fragment carrying the PHO80 gene was sequenced and one open reading frame large enough to encode 293 amino acids was found in the sequence. Northern blot analysis of poly(A)+-RNA isolated from cells grown under repressed and derepressed conditions revealed that (i) the size of the PHO80 message was around 1.4 kb, (ii) the expression of the PHO80 gene was not affected by the presence or absence of inorganic phosphate in the medium, and (iii) the expression of the PHO80 gene was not affected by pho2, pho4, pho81, or by pho80 itself. A centromere sequence was found downstream of the PHO80 coding region.

Acid Phosphatase↗
PubMed1986

Enhancement of cyclic adenosine monophosphate content in bone cells by the factor extracted from a pancreatic cancer associated with hypercalcemia.

A woman with exocrine pancreatic cancer presented a syndrome of humoral hypercalcemia of malignancy (HHM). Either urea extract or acid/ethanol extract of the tumor showed a dose-dependent activity to elevate cyclic adenosine monophosphate (AMP) level in rat bone cells in primary culture. When each population obtained by the sequential digestion of rat fetal calvaria was cultured individually and cyclic AMP responses to parathyroid hormone (PTH), calcitonin, and tumor extract were examined, tumor extract-sensitive cells showed a similar distribution to PTH-sensitive cells. Tumor extract and PTH, but not calcitonin, increased cyclic AMP in osteogenic cell line MC 3T3-E1. PTH receptor-mediated increase of cyclic AMP was indicated by an antagonistic action of PTH analogue, (3-34) hPTH, on increase of cyclic AMP in MC 3T3-E1 elicited by tumor extract. Human breast cancer derived cell line MCF-7 had calcitonin-sensitive adenylate cyclase, but neither PTH nor tumor extract increased cyclic AMP in the cells. On Bio-Gel P-60 column, the activity to stimulate bone cell cyclic AMP was eluted as a single peak at the molecular size between 6.5 K and 12.4 K. It was concluded that pancreatic cancer, although rather exceptional as a cause of HHM, produced a factor very similar to that reported in representative HHM tumors of human and animal models.

Animals↗
PubMed1986

Impaired mineral metabolism in Cushing's syndrome: parathyroid function, vitamin D metabolites and osteopenia.

To clarify the mechanism for the impaired mineral metabolism in Cushing's syndrome, the clinical features, biochemical parameters before and after oral calcium load, and vitamin D metabolism were compared between two groups of patients of endogenous Cushing's syndrome (17 cases) with and without osteopenia. The patients with osteopenia [OP (+): 7 cases, all female] were older (42.7 +/- 8.3 y. o.) and had a longer duration (117 +/- 75 M) of the syndrome than those without osteopenia [OP (-): 33.8 +/- 8.9 y. o., 36 +/- 25 M]. OP (-) showed a blunted hypercalciuria after oral calcium load (63.7 +/- 20.4 to 90.9 +/- 36.1 mg/g X Cr), while OP (+) had higher levels of urinary excretion of calcium (fasting: 120.4 +/- 37.5, and after oral calcium load: 235.6 +/- 72.6 mg/g X Cr), of cyclic AMP (7.6 +/- 1.1 nmol/dl X GF), and of plasma 1.25(OH)2D (76.6 +/- 34.0 pg/ml) than OP (-) (u-cAMP: 3.2 +/- 2.0 nmol/dl X GF, 1,25(OH)2D: 27.9 +/- 16.3 pg/ml). These results indicate that 1) elderly female patients with Cushing's syndrome of long duration are susceptible to OP, 2) during the early phases of the syndrome, reduced intestinal calcium absorption with sustained calciuria (probably through the inhibition of calcium reabsorptive effect of PTH by glucocorticoid) induces negative calcium balance, leading to 3) a development of secondary hyperparathyroidism which stimulates 1,25(OH)2D synthesis. Thus, the mechanism involving bone resorption stimulated by excess PTH along with the direct inhibition of bone formation by glucocorticoid seems to play an important role in a progressive development of OP in Cushing's syndrome.

Adult↗
PubMed1986

The calcium antagonist diltiazem inhibits calcification enhanced by calcitonin in growth cartilage of rats in ethane-1-hydroxy-1,1-diphosphonate (EHDP)-induced rickets.

In an animal model of human rickets developed by giving a short-term administration of large doses of EHDP to young rats, concomitant administration of [Asu1,7]eel calcitonin (CT) with EHDP resulted in the promotion of calcification in growth cartilage. In an attempt to clarify the mechanisms related to the accelerated calcification due to CT, the effects of diltiazem, a calcium antagonist, were studied. Diltiazem suppressed, in a dose-dependent manner, the accelerated calcification due to CT in the growth cartilage, as determined by findings on the soft X-ray photos, contact microradiograph and light microscopic histology of the proximal region of the tibia. This suppression was only evident when diltiazem and CT were given concomitantly. If it is assumed that diltiazem inhibits the entry of calcium ion into the cells of growth cartilage, in the same manner as seen in case of smooth muscle and myocardial cells, then our results indicate that intracellular concentrations of calcium might play an important role in the occurrence of accelerated calcification due to CT.

Animals↗