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Y H Sun

Publications and source records attributed to Y H Sun.

At least 37 records · Page 2Linked to original sources
PubMed1998

The Homothorax homeoprotein activates the nuclear localization of another homeoprotein, extradenticle, and suppresses eye development in Drosophila.

The Extradenticle (Exd) protein in Drosophila acts as a cofactor to homeotic proteins. Its nuclear localization is regulated. We report the cloning of the Drosophila homothorax (hth) gene, a homolog of the mouse Meis1 proto-oncogene that has a homeobox related to that of exd. Comparison with Meis1 finds two regions of high homology: a novel MH domain and the homeodomain. In imaginal discs, hth expression coincides with nuclear Exd. hth and exd also have virtually identical, mutant clonal phenotypes in adults. These results suggest that hth and exd function in the same pathway. We show that hth acts upstream of exd and is required and sufficient for Exd protein nuclear localization. We also show that hth and exd are both negative regulators of eye development; their mutant clones caused ectopic eye formation. Targeted expression of hth, but not of exd, in the eye disc abolished eye development completely. We suggest that hth acts with exd to delimit the eye field and prevent inappropriate eye development.

Amino Acid Sequence↗
PubMed1998

Identification and characterization of the SMT3 cDNA and gene encoding ubiquitin-like protein from Drosophila melanogaster.

A SMT3 cDNA encoding ubiquitin-like protein from Drosophila melanogaster was isolated and sequenced. Drosophila SMT3 genomic DNA was amplified by polymerase chain reaction, and its nucleotide sequence was found to be identical to that of the cDNA, indicating the absence of intron in its protein coding region. The sequence of 90 amino acids of Drosophila SMT3 exhibited 55%, 73%, 70% and 52% identity to yeast SMT3, human SMT3A, SMT3B and SMT3C protein.

Amino Acid Sequence↗
PubMed1998

HPV-16 E7 protein bypasses keratinocyte growth inhibition by serum and calcium.

The E6 and E7 genes of HPV-16 or HPV-18 both are necessary for effective immortalization of primary human genital keratinocytes. To analyse the individual role of E6 and E7 genes in dysregulating cell growth, we cloned the HPV-16 E6, E7 and E6/E7 genes into retroviruses. Primary human keratinocytes (PHK) were then infected with these retroviruses and selected in differentiation-inducing medium (high calcium and serum). The E6/E7 retroviruses were the most effective at inducing differentiation-resistant colonies. Intermediate numbers of colonies were induced by E6 and low numbers by E7. Interestingly, only cultures infected with E7 and E6/E7 retroviruses showed a significant proportion of cells progressing into the S phase, consistent with our earlier studies showing that E7 is required for the efficient immortalization of genital keratinocytes. Accompanying this entry into S phase, the E7 or E6/E7 transduced cells expressed high levels of cyclins A, B and E, but lower levels of cyclin D. In addition, cdc-2, cdk-2 and cdk-4 were also increased. No significant differences were detected in the expression of c-myc and c-fos between the vector and any of the transduced cells. Keratinocytes infected with the E7 retrovirus exhibited decreased levels of Rb protein and increased levels of p53, whereas cells infected with E6-expressing retroviruses displayed normal levels of Rb protein and decreased levels of p53. Finally, E7 induced a three-fold increase in bcl-2 expression. Our results indicate that the HPV-16 E7 gene alone is sufficient to bypass keratinoctye growth arrest induced by serum and calcium exposure and that the discordant expression of several cell regulatory proteins accompanies this unregulated proliferation.

Calcium↗
PubMed1998

Selective induction of apoptosis of NB4 cells from G2+M phase by sodium arsenite at lower doses.

Apoptosis of NB4 cells induced by sodium arsenite and arsenate was studied using flow cytometry and DNA gel electrophoresis in order to investigate their effects on cell cycle and determine the relationship between apoptosis and cell cycle. In this study, we found that: 1) at low doses, sodium arsenite selectively induced apoptosis of NB4 cells in G2+M phase of cell cycle after its being arrested in G2 phase. With increment of the cells blocked in G2 phase, dUTP-specifically labeling cells in G2+M phase increased without concomitant increment of dUTP-labeling cells in other two phases of cell cycle; 2) at high doses, extensive apoptosis was induced in NB4 cells from all phases of cell cycle without cell cycle preference and cell cycle blockade; 3) sodium arsenite-induced apoptosis of NB4 cells occurred in the presence of bcl-2 expression as the unapoptotic cells; 4) sodium arsenite with As3+ induced apoptosis of NB4 cells more strongly than sodium arsenate with As5+ did although both of them affected NB4 cells in the same pattern. These results not only suggested that both arsenite and arsenate induced apoptosis of NB4 cells through 2 different mechanisms--at low doses, arsenical might directly induce apoptosis through regulation of cell cycle checkpoint, while at high doses they might directly induce it, but also indicated that bcl-2 might not play an important role in arsenite or arsenate-induced apoptosis of NB4 cells, whereas chemical valence of As in a compound might be related to efficiency in arsenical induction of apoptosis.

Apoptosis↗
PubMed1998

The Drosophila Pax gene eye gone is required for embryonic salivary duct development.

What are the developmental mechanisms required for conversion of an undifferentiated, two-dimensional field of cells into a patterned, tubular organ? In this report, we describe the contribution of the Drosophila Pax gene eye gone to the development of the embryonic salivary glands and ducts. eye gone expression in salivary tissues is controlled by several known regulators of salivary fate. After the initial establishment of the salivary primordium by Sex combs reduced, fork head excludes eye gone expression from the pregland cells so that its salivary expression is restricted to the posterior preduct cells. trachealess, in contrast, activates eye gone expression in the posterior preduct cells. We have previously described the process by which fork head and the EGF receptor pathway define the border between the gland and duct primordia. Here we show that eye gone is required for the subdivision of the duct primordium itself into the posterior individual duct and the anterior common duct domains. In the absence of eye gone, individual ducts as well as the precursor of the adult salivary glands, the imaginal ring, are absent. We took advantage of this ductless phenotype to show that Drosophila larvae do not have an obligate requirement for salivary glands and ducts. In addition to its role in the salivary duct, eye gone is required in the embryo for the development of the eye-antennal imaginal disc and the chemosensory antennal organ.

Animals↗
PubMed1998

Dorsotonals/homothorax, the Drosophila homologue of meis1, interacts with extradenticle in patterning of the embryonic PNS.

The homeotic genes of the bithorax complex are required, among other things, for establishing the patterns of sensory organs in the embryonic peripheral nervous system (PNS). However, the molecular mechanisms by which these genes affect pattern formation in the PNS are not understood and other genes that function in this pathway are not characterized. Here we report the phenotypic and molecular analysis of one such gene, homothorax (hth; also named dorsotonals). Mutations in the hth gene seem to alter the identity of the abdominal chordotonal neurons, which depend on Abd-A for their normal development. However, these mutations do not alter the expression of the abd-A gene, suggesting that hth may be involved in modulating abd-A activity. We have generated multiple mutations in the hth locus and cloned the hth gene. hth encodes a homeodomain-containing protein that is most similar to the murine proto-oncogene meis1. The hth gene is expressed throughout embryonic development in a spatially restricted pattern, which is modulated in abdominal segments by abd-A and Ubx. The spatial distribution of the HTH protein during embryonic development is very similar to the distribution of the Extradenticle (EXD) protein, a known modulator of homeotic gene activity. Here we show that the PNS phenotype of exd mutant embryos is virtually indistinguishable from that of hth mutant embryos and does not simply follow the homeotic transformations observed in the epidermis. We also show that the HTH protein is present in extremely low levels in embryos lacking exd activity as compared to wild-type embryos. In contrast, the EXD protein is present in fairly normal levels in hth mutant embryos, but fails to accumulate in nuclei and remains cytoplasmic. Ectopic expression of hth can drive ectopic nuclear localization of EXD. Based on our observations we propose that the genetic interactions between hth and exd serve as a novel mechanism for regulating homeotic protein activity in embryonic PNS development.

Alleles↗
PubMed1997

Gypsy retrotransposon as a tool for the in vivo analysis of the regulatory region of the optomotor-blind gene in Drosophila.

We report here a method for the in vivo dissection of the regulatory region of a gene in the Drosophila genome. Our system includes (i) the reporter genes lacZ and white to detect transcriptional enhancer and silencer activities in a target gene, (ii) an efficient way to induce integration of gypsy elements in the genome, and (iii) unidirectional blocking of regulatory activities by the gypsy element, which is dependent on the su(Hw) protein. The optomotor-blind (omb) gene was analyzed. In the omb(P1) line, a P[lacW] construct is inserted about 1.4 kb upstream of the omb transcription start site. The lacZ reporter gene within P[lacW] exhibits the same expression pattern as omb. The white reporter gene is expressed in a "bipolar" pattern. We induced high frequency gypsy mobilization in omb(P1) and identified two lines (D11 and D13-1) with altered eye pigmentation pattern, which is dependent on su(Hw) activity. A gypsy element was found inserted in the first intron of omb in D13-1 and in P[lacW] in D11. These results indicate that it is the blocking of regulatory activities by gypsy that caused the changes in the white reporter gene expression. The effect of these gypsy insertions on the expression patterns allowed us to predict several aspects of the organization of the regulatory elements in the omb locus.

Animals↗
PubMed1997

Wave-intensity analysis: a new approach to left ventricular filling dynamics.

In order to explore a new approach to the analysis of diastolic dysfunction, we adapted wave-intensity analysis (WIA), a time-domain analysis that provides information regarding both upstream and downstream events, to left ventricular (LV) filling. WIA considers the pressure and flow waves as summations of successive wavelets, characterised by the direction they travel and by the sign of the pressure gradient associated with them. Wave intensity is the product, dPdU, calculated from the incremental differences in LV pressure (dP) and mitral velocity (dU) and, during the diastolic filling interval, yields up to five dPdU peaks. Peak 1 is caused by backward-travelling expansion waves that accelerate the blood while LV pressure falls, and may be related to "diastolic suction". Peak 2 is caused by forward-travelling compression waves which occur if acceleration continues after LV pressure begins to increase. Peak 3 is caused by backward compression waves and is associated with rising LV pressure and deceleration. Peak 4 is caused by forward compression waves and is associated with the increasing LV pressure and acceleration caused by atrial contraction. Peak 5 is caused by backward compression waves and is associated with increasing pressure and deceleration. These preliminary observations suggest that WIA can be useful in describing the mechanics of LV filling and, after much further work has been accomplished, it might prove useful in the detection and characterization of diastolic dysfunction.

Aorta↗
PubMed1997

A preceding airway reaction to one allergen may lead to priming of the airway responses to another allergen.

This study aimed to determine whether a preceding airway response to one allergen leads to priming of the airway responses to another allergen. Twelve asthmatic children who had positive prick tests to two allergens, Dermatophagoides pteronyssinus (D.p.) and German cockroach (CR), participated in a randomized, placebo-controlled crossover study. We performed two consecutive inhalation challenges, D.p. challenge being followed 48 h later by CR challenge. The effect of initial (D.p.) challenge on the early and late airway responses to the subsequent (CR) challenge (CR2) was examined by comparing the responses with those to CR challenge preceded by sham challenge (CR1). The geometric mean PD20 of CR allergen in the CR2 was 2.8 BU (breath unit) (range of 1 SD; 0.77-10.4), which was 12.0-fold less than that (33.7 BU, 10.8-105.2) in the CR1. The administration of a 6.1-fold less dose (8.9 BU, 2.7-28.8) in the CR2 than in the CR1 (54.5 BU, 44.1-69.3) provoked a similar degree of late-phase reactions (18.7 +/- 7.3% vs 15.8 +/- 9.6%). Our data indicated that the early- and late-phase reactions to CR challenge were augmented by the preceding reaction to D.p. This suggests that a preceding airway response to one allergen may lead to priming, with enhancement of the early and late airway responses to the subsequent challenge with another allergen.

Adolescent↗
PubMed1997

Effect of roxithromycin on airway responsiveness in children with bronchiectasis: a double-blind, placebo-controlled study.

Increased airway responsiveness (AR) is frequently associated with bronchiectasis. Roxithromycin is a new semisynthetic macrolide antibiotic that also has anti-inflammatory activities. This study was designed to see whether roxithromycin could favourably alter the degree of AR in patients with bronchiectasis and increased AR. Twenty five children with bronchiectasis, who had an increased AR (defined as a provocative concentration of methacholine causing a 20% fall in forced expiratory volume in one second (FEV1) (PC20) <25 mg x mL(-1) evaluated by the dosimeter method), were randomized, double-blind into two parallel groups. Thirteen of the children were treated with roxithromycin (4 mg x kg(-1) b.i.d.) for 12 weeks and 12 received placebo. FEV1, sputum purulence and leucocyte scores were assessed every 3 weeks. To estimate AR, high-dose methacholine challenge tests were performed before and after treatment. On the dose-response curve to methacholine, PD20 and maximal response (two indices of AR) were measured. Changes in FEV1 were not observed during the course of the study in both groups. A significant improvement in sputum features was noted after 6 weeks of treatment in the roxithromycin group. After 12 weeks of roxithromycin therapy, the geometric mean (range of 1 SD) of provocative cumulative dose producing a 20% fall in FEV1 (PD20) increased significantly (p<0.01) to 169.2 (83.2-344.2) breath units (BU) (1 BU denotes one inhalation of 1 mg x mL(-1) methacholine) and the mean+/-SD of maximal response decreased significantly (p<0.01) to 32.5+/-6.8%, as compared with the initial values (PD20 87.1 (47.3-160.4) BU; maximal response 40.9+/-7.4%). No significant changes in either parameter were observed in the placebo group. Our results indicate that roxithromycin may decrease the degree of airway responsiveness in patients with bronchiectasis and increased airway responsiveness. Further study is necessary to determine the mechanism by which roxithromycin reduces airway responsiveness in bronchiectasis and its clinical impact.

Adolescent↗
PubMed1997

[In vitro growth characteristics of rIL3 stimulated megakaryocytic progenitor cells (CFU-MK) of fetal liver].

In this study, plasma clot and methycellulose semi-solid and liquid culture technigues were employed to observe the in vitro growth characteristics of proliferation and differetiation of 4-5 months fetal liver and adult bone marrow CFU-MKs. Fetal liver MK colonies in plasma clot in the presence of rIL3 or Meg-CSA were larger (usually with > 50 cells/colony) than that of the adult (usually with < 50 cells/colony). The number (36.40 +/- 16.60/1 x 10(5) cells) of fetal liver Mk colonies in presence of 2 ng/ml rIL3 was larger than that (10.05 +/- 2.81/1 x 10(5) cells) of human adult bone marrow MK colonies (P < 0.01). In contrast, the major DNA ploidy classes of megakaryocytes derived from fetal liver CFU-MK were those of 2N and 4N cells and the major DNA ploidy classes of megakaryocytes derived from human adult bone marrow were those of 8N and 4N cells. The mean (5.45 +/- 0.86) of the ploidy of the former was lower than that (10.13 +/- 1.30) of the latter (P < 0.01). The same results were obtained with the presence of 10% Meg-CSA. These present results indicated that CFU-MK in fetal liver has a high ability of proliferation and low capacity of differentiation (polyploidization). Interestingly, the number of fetal liver MK colonies increased in the range of rIL3 concentration from 0.5 ng/ml to 2 ng/ml. At higher rIL3 concentration (2-8 ng/ml), the colony growth showed a steady decrease from the maximum value instead of an increase. However, in the same range of rIL3 concentration, the numbers of adult bone marrow MK colonies numbers and fetal liver CFU-GM colonies increased steadily and finally reached to a plateau. Furthermore, both fetal liver and adult bone marrow MK colonies showed dose-dependent response in the range of Meg-CSA concentration from 5% to 25%. In addition, there was no difference on DNA ploidy distributions of megakaryocytes derived from fetal liver CFU-MK between rIL3 and Meg-CSA as growth factors. Moreover, the DNA ploidy distribution of fetal liver derived megakaryocytes stimulited by rIL3 could not be changed by addition of rIL6 (100 u/ml). In summary, the above data suggest that CFU-MK in the fetal liver undergoes some intrinsic cellular modification in order to suit the need of ontogensis.

Adult↗
PubMed1996

Microbial hydroxylation of 13-ethyl-17 beta-hydroxy-18,19-dinor-17 alpha-pregn-4-en-20-yn-3-one.

The microbial transformation of the racemic mixture of 13-ethyl-17 beta-hydroxy-18,19-dinor-17 alpha-pregn-4-en-20-yn-3-one (1) was investigated. Rhizopus nigricans (AS 3.2050), R. arrhizus (AS 3.4523), Aspergillus niger (AS 3.2744), A. ochraceus (AS 3.1408), and Curvularia lunata (NRRL 4381) transformed 1 into its 10 beta-hydroxy derivative (2) as a major metabolite. Biotransformation of 1 by Aspergillus ochraceus AS 3.1408 afforded 7 beta-hydroxy derivative (3) as the only product.

Aspergillus↗
PubMed1996

Developmental change of megakaryocyte maturation and DNA ploidy in human fetus.

Megakaryocytes in fetal livers obtained from 30 water-balloon aborted normal fetuses of 3 to 6 months' gestation, in the bone marrow from the same 30 fetuses, and another 9 fetuses of 7 to 8 months' gestation and in the normal bone marrow of adults were analyzed by immunocytochemical staining for size and maturation stage distribution and by flow cytometry for ploidy distribution simultaneously. In human fetuses, megakaryocytes showed a shift during ontogenesis from smaller towards larger size and from less mature towards a more mature stage with advancement of gestation. This was accompanied by a significant progressive shift to higher ploidy. However, the proportions (78.64%) of hypoploidy (< or = 8N) megakaryocytes in bone marrow of 7-8 months' gestation fetuses was still much higher than that (33.32%) in human adults (p < 0.05), with the proportion of hyperploidy (> or = 16N) megakaryocytes lower than that (67.86%) in human adults. This result indicated that megakaryocyte polyploidization may be retarded or inhibited during development.

Adult↗
PubMed1995

Expression of a Drosophila GATA transcription factor in multiple tissues in the developing embryos. Identification of homozygous lethal mutants with P-element insertion at the promoter region.

GATA transcription factors are DNA-binding proteins that recognize the core consensus sequence, WGATAR. Previous studies indicated that GATA factors play ann important role in the development of tissue-specific functions in vertebrates. Here we report the identification of a new Drosophila melanogaster GATA factor, dGATAc, which displays a distinct expression pattern in embryos. The local concentration of dGATAc transcripts varies at different stages, being most prominent in the procephalic region at stages 6-10 and in the posterior spiracles, the gut, and the central nervous system at stages 11-13. On the basis of its predicted sequence, DNA-binding assays were performed to confirm that the dGATAc gene encodes a zinc finger protein that can bind the GATA consensus motif with predicted specificity. Two independent mutants carrying a P-element insertion at the dGATAc gene promoter region were identified that are homozygous lethal at the embryonic stage. Using a genetic scheme, it was demonstrated that the lack of dGATAc function can block normal embryonic development. Our results suggest that the dGATAc protein is a tissue-specific transcription factor that is vital to the development of multiple organ systems in D. melanogaster.

Amino Acid Sequence↗
PubMed1995

White as a reporter gene to detect transcriptional silencers specifying position-specific gene expression during Drosophila melanogaster eye development.

The white+ gene was used as a reporter to detect transcriptional silencer activity in the Drosophila genome. Changes in the spatial expression pattern of white were scored in the adult eye as nonuniform patterns of pigmentation. Thirty-six independent P[lacW] transposant lines were collected. These represent 12 distinct pigmentation patterns and probably 21 loci. The spatial pigmentation pattern is due to cis-acting suppression of white+ expression, and the suppression probably depends on cell position rather than cell type. The mechanism of suppression differs from inactivation by heterochromatin. In addition, activation of lacZ in P[lacW] occurs also in specific patterns in imaginal discs and embryos in many of the lines. The expression patterns of white+ and lacZ may reflect the activity of regulatory elements belonging to an endogenous gene near each P[lacW] insertion site. We speculate that these putative POSE (position-specific expression) genes may have a role in pattern formation of the eye as well as other imaginal structures. Three of the loci identified are optomotor-blind, engrailed and invected. teashirt is also implicated as a candidate gene. We propose that this "silencer trap"' may be an efficient way of identifying genes involved in imaginal pattern formation.

ATP-Binding Cassette Transporters↗
PubMed1993

Increased release of immunoreactive cholecystokinin octapeptide by morphine and potentiation of mu-opioid analgesia by CCKB receptor antagonist L-365,260 in rat spinal cord.

This is the first report showing, in an in vivo study, that systemic morphine produced a marked (89%, P < 0.01) increase of the cholecystokinin octapeptide (CCK-8) immunoreactivity in the perfusate of the rat spinal cord, an effect completely reversed by naloxone. Since CCK-8 has been shown to possess potent anti-opioid activity at a spinal level, a blockade of the spinal cholecystokinin effect would be expected to potentiate opiate analgesia. With tail flick latency as a nociceptive index, it was found that intrathecal (i.t.) injection of a novel CCKB antagonist L-365,260 produced a marked potentiation of the analgesic effect induced by the mu-opioid agonists morphine (4 mg/kg s.c.) or ohmefentanyl (32 ng i.t.). Similar effects were obtained with the CCKA antagonist devazepide at a dose 40-50 times higher than that of L-365,260. Both devazepide and L-365,260 showed a bell-shaped dose-response curve. The results confirm the notion that an increased release of CCK-8 may constitute a self-limiting process for opioid effects at the spinal level, and that it is the CCKB receptor which mediates the anti-opioid effect of CCK-8 in the rat spinal cord.

Analgesia↗
PubMed1993

Treatment of intra-articular fractures with shape memory compression staples.

The management of intra-articular fractures remains difficult. Shape memory compression staples fulfil nearly all the special treatment requirements of intra-articular fractures. Early bone union and 93.5 per cent satisfactory function were achieved in a series of 121 cases. Stable fixation, 'early' movement and continuous compressive force produced by the staple are the main factors contributing to good results.

Adolescent↗