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T Aso

Publications and source records attributed to T Aso.

At least 91 records · Page 5Linked to original sources
PubMed1999

CRTH2, an orphan receptor of T-helper-2-cells, is expressed on basophils and eosinophils and responds to mast cell-derived factor(s).

We have recently cloned a putative chemoattractant receptor, named CRTH2, which is preferentially expressed on human T-helper- (Th) 2 but not Th1 cells. In this study, we demonstrated that CRTH2 is also highly expressed on peripheral blood basophils and eosinophils. Our search for a CRTH2 ligand identified mast cells as the possible producers of a ligand. When stimulated with an anti-FcepsilonR1 antibody, cord blood-derived mast cells secreted factor(s) that induced Ca(2+) mobilization in CRTH2-expressing K562 cells but not in mock transfected cells. These findings implied the involvement of CRTH2 in mast cell-mediated immune responses such as allergic reactions.

Basophils↗
PubMed1999

Physical interaction and functional antagonism between the RNA polymerase II elongation factor ELL and p53.

ELL was originally identified as a gene that undergoes translocation with the trithorax-like MLL gene in acute myeloid leukemia. Recent studies have shown that the gene product, ELL, functions as an RNA polymerase II elongation factor that increases the rate of transcription by RNA polymerase II by suppressing transient pausing. Using yeast two-hybrid screening with ELL as bait, we isolated the p53 tumor suppressor protein as a specific interactor of ELL. The interaction involves respectively the transcription elongation activation domain of ELL and the C-terminal tail of p53. Through this interaction, ELL inhibits both sequence-specific transactivation and sequence-independent transrepression by p53. Thus, ELL acts as a negative regulator of p53 in transcription. Conversely, p53 inhibits the transcription elongation activity of ELL, suggesting that p53 is capable of regulating general transcription by RNA polymerase II through controlling the ELL activity. Elevated levels of ELL in cells resulted in the inhibition of p53-dependent induction of endogenous p21 and substantially protected cells from p53-mediated apoptosis that is induced by genotoxic stress. Our observations indicate the existence of a mutually inhibitory interaction between p53 and a general transcription elongation factor ELL and raise the possibility that an aberrant interaction between p53 and ELL may play a role in the genesis of leukemias carrying MLL-ELL gene translocations.

Cell Compartmentation↗
PubMed1999

Gestational changes in endothelin-1-induced receptors and myometrial contractions in rat.

The present experiments were performed to characterize the gestational changes in endothelin (ET)-1-induced myometrial contractions and ET receptors in rat. ET-1-induced contractions were composed of two types: increases in resting tone and rhythmic contractions. The increase in resting tone was decreased at 7 days of gestation, but increased at 20 days. The increase in amplitude and frequency of rhythmic contractions remained unchanged during days 7-14 of gestation. Continuous rhythmic contractions were not produced by ET-1 near the term. Both contractions were inhibited by the antagonists BQ 123 and Ro 46-2005 but not by RES 701-1 or BQ 788. In binding studies, total binding sites of [1251]-ET-1 were unchanged, however higher affinity binding sites appeared during pregnancy in addition to the lower affinity sites. The specific [125I]-ET-1 binding in non-pregnant and pregnant myometrium was completely inhibited by unlabelled ET-1 and Ro 46-2005. In contrast, the proportion which was inhibited by BQ 123 was decreased during pregnancy. In conclusion, characteristic gestational changes were the augmentation of ET-1-induced increased resting tone near term, and the appearance of high affinity ET-1 binding sites and an increase in BQ 123-resistant ET-1 binding sites during pregnancy. Further investigations are needed to understand the physiological role of these changes.

Animals↗
PubMed1999

Expression of inducible nitric oxide synthase in human cultured endometrial stromal cells.

The aim of the present study was to investigate the expression of mRNA and protein for inducible nitric oxide synthase (iNOS) in human cultured endometrial stromal cells. The endometrial stromal cells were cultured in the absence or the presence of cytokines such as interleukin (IL)-1beta and interferon (IFN)-gamma, which are inherently detectable in the endometrium. Nested reverse transcription-polymerase chain reaction detected iNOS mRNA in stromal cells cultured without cytokines. Northern blot analysis failed to detect iNOS mRNA in stromal cells cultured for 9 h in the absence of cytokines or in the presence of IL-1beta (10-100 ng/ml) or IFN-gamma (10-1000 U/ml) alone, but could detect iNOS mRNA cultured in combinations of IL-1beta and IFN-gamma. The concentrations of iNOS mRNA were increased as early as 3 h after the addition of the cytokine combination and persisted for up to 36 h. Western blot analysis demonstrated iNOS protein in stromal cells cultured for 12 h with combined IL-1beta and IFN-gamma. These results raise the possibility that nitric oxide locally synthesized by iNOS may be involved in the control of endometrial functions.

Adult↗
PubMed1999

Structural organization and chromosome location of the mouse elongin A gene (Tceb3).

Elongin A is the transcriptionally active subunit of the Elongin complex, which strongly increases the rate of elongation by RNA polymerase II by suppressing the transient pausing of the polymerase at many sites within transcription units. In the present study, we obtained the cDNA sequence of the mouse Elongin A gene (Tceb3) and characterized its genomic structure. The deduced 773-amino acid sequence of mouse Elongin A shows 91% and 81% identity with rat and human Elongin A, respectively. The Elongin A gene was mapped to mouse chromosome 4D3 by fluorescence in situ hybridization.

Amino Acid Sequence↗
PubMed1999

Synthetic peptides define critical contacts between elongin C, elongin B, and the von Hippel-Lindau protein.

The von Hippel-Lindau tumor suppressor protein (pVHL) negatively regulates hypoxia-inducible mRNAs such as the mRNA encoding vascular endothelial growth factor (VEGF). This activity has been linked to its ability to form multimeric complexes that contain elongin C, elongin B, and Cul2. To understand this process in greater detail, we performed a series of in vitro binding assays using pVHL, elongin B, and elongin C variants as well as synthetic peptide competitors derived from pVHL or elongin C. A subdomain of elongin C (residues 17-50) was necessary and sufficient for detectable binding to elongin B. In contrast, elongin B residues required for binding to elongin C were not confined to a discrete colinear domain. We found that the pVHL (residues 157-171) is necessary and sufficient for binding to elongin C in vitro and is frequently mutated in families with VHL disease. These mutations preferentially involve residues that directly bind to elongin C and/or alter the conformation of pVHL such that binding to elongin C is at least partially diminished. These results are consistent with the view that diminished binding of pVHL to the elongins plays a causal role in VHL disease.

Amino Acid Sequence↗
PubMed1999

Immunohistochemical localization of tenascin and ki-67 nuclear antigen in human endometrium throughout the normal menstrual cycle.

To elucidate the possible regulation of endometrial growth, we investigated the expression of tenascin, an extracellular matrix protein associated with cell proliferation and morphogenetic events, in relation to the mitotic marker ki-67 antigen in human endometrium throughout the menstrual cycle. The endometrial tissue was obtained from women with regular menstruation undergoing hysterectomy due to benign uterine disease. Cryostat sections were subjected to double immunohistochemistry to detect both tenascin and ki-67. During the proliferative phase, an intense deposition of tenascin fibrils occurred in the extracellular matrix of the stroma immediately subjacent to the uterine epithelium that showed the highest proportion of ki-67 positive cells. In the secretory phase, the amount of tenascin expression and the proliferative index of the epithelium were markedly reduced. The topological immunoreactivity of tenascin, however, was clearly related to ki-67 localization close to the tortuous endometrial gland and spiral artery. Expression of tenascin, showing changes depending on the menstrual phase, appears to be influenced by ovarian steroid hormones, and it might play a role in regulating human endometrial development by interaction with mitotic cells.

Adult↗
PubMed1998

Study on myofibroblast differentiation in the stromal cells of Wharton's jelly: expression and localization of alpha-smooth muscle actin.

To confirm the characteristics of the stromal cells of Wharton's jelly, we investigated the morphological changes in these cells during each trimester of pregnancy. We evaluated the cytoskeletal features of these cells by examining immunohistochemically the localization of one of the contractile proteins, alpha-smooth muscle actin (ASMA). After the second trimester, the stromal cells of Wharton's jelly were stained with ASMA antibody, exhibited the ultrastructural characteristics of the myofibroblasts, and began to express numerous microfilaments in the cytoplasm. Postembedding immunogold labeling detected immunoreactivity for ASMA on these microfilaments. The finding indicated that the stromal cells of Wharton's jelly undergo a time-dependent maturation involving the differentiation of myofibroblasts during the last 6 months of pregnancy. These cells possess a contractile function that may help to protect the umbilical vessels from compression, considering that ASMA was detected in the microfilamentous bundles.

Actins↗
PubMed1998

Species differences in the disposition of propranolol prodrugs derived from hydrolase activity in intestinal mucosa.

The bioavailability of propranolol (PL) after oral administration of ester-type prodrug was compared in rat and dog, and the possible reason for species difference was investigated. In dog, the oral bioavailability of PL was enhanced by the use of prodrug due to saturation of metabolism of PL. In contrast, high (10 mg/kg) and low (2.5 mg/kg) doses of butyryl PL and isovaleryl PL failed to improve oral bioavailability of PL in rats. The hydrolase activities for prodrugs in rat liver were lower than those of dog (by 4-12-fold), but those of rat intestinal mucosa were significantly higher than those of dog (50-260-fold). Although it is clear from the in vitro hydrolysis using subcellular fractions that the rapid hydrolysis in intestinal mucosa was mainly due to cytosolic components, the brush-border membrane vesicle in rat intestine also showed hydrolase activity for both prodrugs. In situ absorption experiment in rat revealed an improvement in the apparent absorption rate of PL as the result of prodrug use (1.3-fold) and the nearly complete hydrolysis of isovaleryl PL during intestinal absorption, which is a slower hydrolyzed prodrug than butyryl PL in intestinal mucosa and liver. The defects for enhancing oral bioavailability in rats appears to be based on an unsaturation of metabolism for PL, which is derived from a decrease in PL concentration in hepatocytes, owing to rapid hydrolysis of the prodrug in intestinal mucosa and slow hydrolysis of the prodrug in liver. Furthermore, human intestinal mucosa showed a surprisingly high hydrolase activity in microsomes. Therefore, the oral bioavailability of PL after administration of prodrugs might be not significantly improved in human.

Administration, Oral↗
PubMed1998

Expression of IL-6 receptor and GP130 in mouse bone marrow cells during osteoclast differentiation.

Interleukin-6 (IL-6) has been postulated as a possible mediator of bone loss after estrogen deficiency, and its signal is transduced via glycoprotein 130 (gp130) after binding IL-6 receptor (IL-6R) in the membrane of target cells. In this study, the expression of IL-6R and gp130 in bone marrow cells during osteoclast differentiation was investigated. Mouse bone marrow cells were isolated and cultured with or without 1alpha,25-dihydroxyvitamin D3 [1,25(OH)2D3]. During the formation of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells (MNCs), IL-6R and gp130 expression in the mononuclear cells, stromal cells, and TRAP-positive MNCs were quantitated, using a laser cytometer with a fluorescence confocal microscopy. With 1,25(OH)2D3 stimulus, the level of gp130 significantly increased, but that of IL-6R did not in the stromal cells. In contrast, the levels of both gp130 and IL-6R significantly increased in the mononuclear cells by the treatment with 1,25(OH)2D3. The high expression of both gp130 and IL-6R was observed in the TRAP-positive mononuclear cells. Moreover, both IL-6R and gp130 were expressed in the TRAP-positive MNCs and isolated murine osteoclasts. The treatment of TRAP-positive MNCs with IL-6 caused enhancement of the resorbing activity in a dose-dependent manner, and the effect was prevented by a neutralizing antibody against IL-6R. These data suggest that gp130 and IL-6R, as well as IL-6, are involved in the formation and activation of osteoclasts.

Acid Phosphatase↗
PubMed1998

Prostaglandins induce calcium influx in human spermatozoa.

Progesterone, prostaglandin and follicular fluid are reported to enhance the acrosome reaction through the influx of extracellular calcium into the cytoplasm of human spermatozoa. Prostaglandins are present within the male reproductive tract, and high concentrations of prostaglandins exist in seminal fluid. In order to investigate the mechanisms by which prostaglandins enhance the acrosome reaction through calcium influx, the intracellular calcium response induced by progesterone, prostaglandin E1 (PGE1), prostaglandin E2 (PGE2) and follicular fluid was measured using fura-2. PGE1 and PGE2 promoted calcium influx dose dependently through dihydropyridine insensitive calcium channels. Refractoriness of the elevation of intracellular Ca2+ concentration ([Ca2+]i) to a second stimulus occurred when 60 microg/ml PGE1 was administered 100 s after the prior administration of 60 microg/ml of PGE1, and similarly when 1 microg/ml of progesterone was administered 100 s after the prior administration of 1 microg/ml of progesterone. Refractoriness also occurred when 60 microg/ml PGE1 was administered after the prior addition of 60 microg/ml PGE2, but did not occur between PGE1 and progesterone. Pertussis toxin (PTX) did not modify the changes in [Ca2+]i after the addition of PGE1 or PGE2. In conclusion, PGE1 and PGE2 promoted calcium influx through PTX-insensitive calcium channels which appeared to be recognized by a common receptor different from that of progesterone.

Acrosome↗
PubMed1998

Role of nitric oxide synthase in release of endothelin from cultured human endometrial cells.

The aim of this study was to investigate the influence of the nitric oxide/nitric oxide synthase (NO/NOS) system on the release of endothelin-1 (ET-1) in human endometrial cells. Human endometrial stromal cells in secretory phase were incubated for 72 h in serum-free RPMI 1640 medium in the absence or presence of different concentrations of interleukin-1beta (IL-1beta) and NG-monomethyl-L-arginine (LNMMA), a specific competitive inhibitor of NOS. ET-1 released from the cultured cells into the medium was determined by specific RIA. In all the experiments at various times, IL-1beta significantly increased the release of ET-1. LNMMA significantly attenuated the release of ET-1 when the cells were cultured with both IL-1beta and LNMMA, but LNMMA alone had no effect on ET-1 release. These results suggest that the NO/NOS system in human endometrium is involved in the regulation of ET-1 release via IL-1beta secretion. It can also be inferred that NO and ET-1 control the functions of endometrium in close association with IL-1beta.

Adult↗
PubMed1997

HDR syndrome (hypoparathyroidism, sensorineural deafness, renal dysplasia) associated with del(10)(p13).

A combination of hypoparathyroidism, sensorineural deafness, and renal dysplasia has been considered to be a new syndrome inherited in an autosomal dominant fashion; we name the condition "HDR syndrome." We describe a Japanese girl who has HDR syndrome associated with de novo del(10)(p13). The chromosome deletion suggests that the putative gene(s) responsible for HDR syndrome is located at a 10pter-->p13 region.

Adult↗