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Biomedical subjects

J Dang

Publications and source records attributed to J Dang.

At least 19 recordsLinked to original sources
PubMed2001

The E2A-HLF oncoprotein activates Groucho-related genes and suppresses Runx1.

The E2A-HLF fusion gene, formed by the t(17;19)(q22;p13) chromosomal translocation in leukemic pro-B cells, encodes a chimeric transcription factor consisting of the transactivation domain of E2A linked to the bZIP DNA-binding and protein dimerization domain of hepatic leukemia factor (HLF). This oncoprotein blocks apoptosis induced by growth factor deprivation or irradiation, but the mechanism for this effect remains unclear. We therefore performed representational difference analysis (RDA) to identify downstream genetic targets of E2A-HLF, using a murine FL5.12 pro-B cell line that had been stably transfected with E2A-HLF cDNA under the control of a zinc-regulated metallothionein promoter. Two RDA clones, designated RDA1 and RDA3, were differentially upregulated in E2A-HLF-positive cells after zinc induction. The corresponding cDNAs encoded two WD40 repeat-containing proteins, Grg2 and Grg6. Both are related to the Drosophila protein Groucho, a transcriptional corepressor that lacks DNA-binding activity on its own but can act in concert with other proteins to regulate embryologic development of the fly. Expression of both Grg2 and Grg6 was upregulated 10- to 50-fold by E2A-HLF. Immunoblot analysis detected increased amounts of two additional Groucho-related proteins, Grg1 and Grg4, in cells expressing E2A-HLF. A mutant E2A-HLF protein with a disabled DNA-binding region also mediated pro-B cell survival and activated Groucho-related genes. Among the transcription factors known to interact with Groucho-related protein, only RUNX1 was appreciably downregulated by E2A-HLF. Our results identify a highly conserved family of transcriptional corepressors that are activated by E2A-HLF, and they suggest that downregulation of RUNX1 may contribute to E2A-HLF-mediated leukemogenesis.

Amino Acid Sequence↗
PubMed2000

Recombinant antibodies: a new reagent for biological agent detection.

Antibodies are critical reagents used in several biodetection platforms for the identification of biological agents. Recent advances in phage display technology allow isolation of high affinity recombinant antibody fragments (Fabs) that may bind unique epitopes of biological threat agents. The versatility of the selection process lends itself to efficient screening methodologies and can increase the number of antigen binding clones that can be isolated. Pilot scale biomanufacturing can then be used for the economical production of these immunoglobulin reagents in bacterial fermentation systems, and expression vectors with hexahistidine tags can be used to simplify downstream purification. One such Fab reagent directed against botulinum neurotoxin A/B has been shown to be sensitive in a variety of assay formats including surface plasmon resonance (SPR), flow cytometry, enzyme linked immunosorbent assay (ELISA), and hand-held immunochromatographic assay. Recombinant antibodies can provide another source of high quality detection reagents in our arsenal to identify or detect pathogens in environmental samples.

Animals↗
PubMed2000

Identification of a novel nuclear factor-kappaB sequence involved in expression of urokinase-type plasminogen activator receptor.

We have previously defined the promoter of human urokinase-type plasminogen activator receptor (uPAR) gene in a 188-bp fragment between bases -141 and +47 relative to the translation start site. Here, we report that a novel nuclear factor-kappaB (NF-kappaB)-like sequence (5'-GGGAGGAGTC-3') at -45 is located in the uPAR promoter and one of the two DNase I-protected regions, region I between bases -51 and -30. This NF-kappaB-like motif differs at positions 7-9 from the decameric consensus sequences of NF-kappaB (5'-GGGRNNYYCC-3' where R indicates A or G, Y indicates C or T, and N indicates any nucleotide) and at positions 1 and 7-9 from the kappaB-like motifs (5'-HGGARNYYCC-3' where H indicates A, C, or T, R indicates A or G, Y indicates C or T, and N indicates any nucleotide). Nuclear extracts from HCT116 cells contain proteins that specifically bind to the NF-kappaB-like site at position -45. Mutation of the NF-kappaB-like motif decreased the binding of transcription factor NF-kappaB and reduced the uPAR promoter activity in comparison with the wild-type sequences. Co-transfection with a dominant negative I-kappaB kinase-2 expression vector reduced uPAR promoter activity by 65-75%. These results demonstrate that a previously uncharacterized NF-kappaB motif is required for uPAR promoter activity.

5' Untranslated Regions↗
PubMed1999

A region between -141 and -61 bp containing a proximal AP-1 is essential for constitutive expression of urokinase-type plasminogen activator receptor.

An 8.5-kb 5'-flanking region of the human urokinase-type plasminogen activator receptor (uPAR) gene was cloned and the detailed uPAR promoter region defined in an 188-bp fragment between bases -141 and +47 relative to the transcription-start site. 5'-Deletion to -100 and -60 in the region abolished its promoter activity, indicating that an 81-bp segment between -141 and -61, which contains a proximal AP-1 site at position -70, is required for uPAR promoter activity. Nuclear extracts from HCT116 cells contain proteins that specifically bind to the AP-1 site. Mutation of the AP-1 motif reduced uPAR promoter activity in comparison with the wild-types. Induction of uPAR expression by phorbol ester requires this AP-1 motif in colon cancer cells. Cotransfection with the c-jun and c-fos expression vectors stimulated the uPAR promoter activity four- to fivefold. These results demonstrate that the proximal AP-1 motif is responsible for approximately 50% of the basal expression of the uPAR gene.

Base Sequence↗
PubMed1998

Clinical preconditions and treatment modality: effects on pulp surgery outcome.

BACKGROUND: The purpose of this research was to evaluate the factors affecting the outcome of localized laser pulp surgery in the canine model. STUDY DESIGN/MATERIALS AND METHODS: Pulpal exposures 2 mm and 5 mm in diameter were prepared in eight healthy teeth in each of five dogs. The total of 40 teeth were left open to infection from the oral cavity for 3 hours or 72 hours; 2-3 mm of surface pulpal tissue were then removed using a fresh diamond bur or a CO2 laser emitting@9.3 microns, at 3.5 W average power in the Superpulse mode. Teeth were monitored clinically and radiographically by one blinded, pre-standardized clinician for 3 months. RESULTS: Chi-square test and Fisher's Exact test (2-tail) results associated laser treatment with significantly better clinical and radiographic outcome (P < 0.001). Using regression analysis, duration of pulpal exposure to contamination by the oral environment was identified as primary determinant for treatment outcome within the laser-treated and control groups (P = 0.0018). CONCLUSION: Clinical preconditions significantly affect the outcome of pulp surgery treatments.

Animals↗
PubMed1998

An experimental study of the open end correction coefficient for side branches within an acoustic tube.

The open end correction coefficient (OECC) of acoustic tubes has been widely investigated under a free-field condition. This study examines OECCs in confined regions, such as side branches within the vocal tract. To do this, a number of mechanical acoustic models are used to examine the effects of the angle of the branch axis and the proximity of the walls of the main tract to the open end of the branch. The OECC is estimated by matching both the peaks and troughs (i.e., spectral maxima and minima) of the computed and measured transfer functions for each model. The results indicate that the OECC of a side branch depends on L/D, where L is the cross dimension of the main tract at the branching point, and D is the branch diameter. For side branches connected to the main tract through a narrow neck, the OECC of each end of the neck is determined using the ratio of the radius of the neck to that of the adjacent section. Two empirical equations for evaluating the OECC within a tract are derived from the present study. Finally, the range of appropriate OECC values for estimating an accurate vocal tract transfer function is discussed, based on the results presented here and morphologic measurements reported previously.

Ear↗
PubMed1997

The influence of laser parameter configurations at 9.3 microns on incisional and collateral effects in soft tissue.

These investigations were performed to determine histologic and incisional consequences of varying pulse duration, duty cycle, and average powers during laser incision at 9.3 microns in soft tissue. In 19 fresh pigs' jaws six standardized incisions 3 cm long were made per parameter with a template and motorized jig. Laser parameters investigated were average power: 1 to 9 W, duty cycle: 10% to 80%, and pulse duration: 1 to 200 msec. The gated Cw mode was used. Incision width and depth and collateral tissue effects were assessed statistically with general linear procedures. Multiple factors were found to influence the outcome of laser irradiation. Depth of incision correlated positively with average power. Tissue damage correlated strongly and negatively with all three variables. These results demonstrate that a wide range of surgical and collateral effects can be achieved with one specific laser device depending on the parameter configuration selected.

Animals↗
PubMed1997

Acoustic characteristics of the piriform fossa in models and humans.

The piriform fossa forms the bottom part of the pharynx and acts as a pair of side branches of the vocal tract. Because of its obscure form and function, the piriform fossa has usually been neglected in the current speech production models. This study examines the geometric and acoustic characteristics of the piriform fossa by means of MRI-based mechanical modeling, in-vivo experiments and numerical computations. Volumetric MRI data showed that the piriform fossa is 2.1 to 2.9 cm3 in volume and 1.6 to 2.0 cm in depth for four Japanese subjects (three males and one female). The results obtained from mechanical models showed that the piriform fossa contributes strong troughs, i.e., spectral minima, to speech spectra in a region of 4 to 5 kHz. The antiresonances were identified with increasing frequency when water was injected into the piriform fossa of human subjects in in-vivo experiments. Antiresonances obtained from the experiments and simulations were confirmed to be consistent with those in natural speech within 5%. Acoustic measurements and simulations showed that the influence of the piriform fossa extends to the lower vowel formants in addition to the local troughs. This global effect can be explained by the location of the fossa near the glottal end of the vocal tract.

Female↗
PubMed1997

Investigating the range of surgical effects on soft tissue produced by a carbon dioxide laser.

The authors investigated the surgical and collateral effects on soft tissue of a carbon dioxide laser emitting at 9.3 micrometers. Specifically, incision widths and depths as well as effectiveness were studied. Three different laser modes were investigated: gated continuous wave, or Cw, Superpulse and OptiPulse (Medical Optics). Incision depths correlated positively with average power; higher powers produced deeper incisions. The gated Cw mode quickly produced wide, deep incisions; Superpulse achieved narrower, deep incisions; OptiPulse caused very narrow, shallow incisions. Collateral damage to adjacent tissues was reduced by a factor of about 2 using Superpulse, and by a factor of 10 using OptiPulse. A wide range of effects is achieved in soft tissue, depending on the laser parameter combination used.

Animals↗
PubMed1996

Acoustic characteristics of the human paranasal sinuses derived from transmission characteristic measurement and morphological observation.

This paper reports on the acoustic characteristics of the paranasal sinuses as determined from transmission characteristic measurements and morphological examinations. A new experimental approach was developed to explore the correspondence between antiresonance frequencies and the causal resonators [J. Dang and K. Honda, J. Acoust. Soc. Jpn. (E) 17, 93-99 (1996)], and it was adopted to determine the antiresonance frequency of each sinus cavity. In this study, the antiresonance frequencies and the locations of the sinus openings were estimated from transmission characteristics of the nasal tract for three subjects, and then MRI-based morphological data for the subjects were used to relate each antiresonance frequency to its causal sinus cavity. The results indicate that each of the three major sinuses, i.e., the sphenoidal, maxillary, and frontal sinuses, contributes its own antiresonances to the transmission characteristics of the nasal tract. The estimated antiresonance frequencies were compared with computed natural frequencies of Helmholtz resonators, and the differences were within 10% for the sinuses. On the basis of the frequency distribution of the sinus antiresonance, the acoustic characteristics of the paranasal sinuses were modeled by four Helmholtz resonators. The simulation with the four-zero model showed that the paranasal sinuses not only introduce antiresonances in the transfer function, but also change the spectral shape of the nasal formants.

Glottis↗
PubMed1995

Sodium butyrate inhibits expression of urokinase and its receptor mRNAs at both transcription and post-transcription levels in colon cancer cells.

The effects of butyrate on the modulation of urokinase plasminogen activator (uPA) and its receptor (uPAR) mRNAs were studied. While both mRNA levels were increased after stimulation by tumor necrosis factor alpha (TNF alpha), phorbol ester (PMA) and cycloheximide, they were inhibited by butyrate at 2.5 to 25 mM. Nuclear run-on transcription assays indicated that uPA mRNA was modulated by butyrate at the transcriptional level but the uPAR gene was regulated at both transcriptional and post-transcriptional levels in the presence or absence of TNF alpha. In the presence of PMA, however, butyrate acts at the post-transcriptional level on both genes.

Butyrates↗
PubMed1995

Structure of the human urokinase receptor gene and its similarity to CD59 and the Ly-6 family.

Urokinase plasminogen activator receptor (uPAR) gene expression has been implicated in many important biological processes including cell invasiveness and migration. The uPAR gene was cloned from a human genomic library by hybridization with a uPAR cDNA. The complete structure of the human uPAR gene, including a 21.23-kb transcription unit with 204 bp 5' and 239 bp 3' flanking sequences, was determined by comparison with the uPAR cDNA sequence. The uPAR gene is composed of seven exons and six introns. The seven exons of 101, 111, 144, 162, 135, 147 and 563 bp are separated by six introns of approximately 2.04, 2.62, 8.42, 0.906, 3.10 and 2.78 kb. Exons 1-7 encode 19, 37, 48, 54, 45, 49 and 83 amino acid residues, respectively. A CpG-rich island and sequences related to the transcription factors AP-1, AP-2, c-Jun and NF kappa B are present, but no potential TATA or CAAT boxes were found in the proximal 5' region of the uPAR gene. Comparison of the exon organization of the uPAR gene with that of human CD59 and murine Ly-6 reveals similarity to all three domains encoded by the uPAR exons (2 + 3), (4 + 5) and (6 + 7). These data enable elucidation of the mechanisms involved in regulation of the uPAR gene expression and provide further evidence that the uPAR gene belongs to the Ly-6 superfamily.

Amino Acid Sequence↗
PubMed1995

Amiloride modulates urokinase gene expression at both transcription and post-transcription levels in human colon cancer cells.

Activity of receptor-bound urokinase plasminogen activator (uPA) on the surface of colon cancer cells appears to be a function of the number of uPA receptors. The regulation of uPA therefore may determine the invasive phenotype. The effects of amiloride on the modulation of uPA mRNA and protein induced by phorbol ester (PMA) and cycloheximide (CHX) were studied in four colon cancer cell lines, HCT116, KM12SM, LIM1215 and LS123. Northern blot analyses showed that PMA induced uPA mRNA that peaked at 2-48 h in HCT116 cells. In all colon cancer cell lines tested, the expression of uPA mRNA by PMA was super-induced after the addition of the protein synthesis inhibitor CHX, suggesting that stimulation of uPA gene expression does not require de novo protein synthesis. uPA mRNA was also induced by CHX alone, indicating that there may be a labile protein which inhibits uPA mRNA processing. Amiloride profoundly inhibited uPA mRNA production at concentrations between 0.1-1 mM in the presence or absence of PMA or CHX. uPA protein levels on the colon cancer cell surface reflected PMA induction and amiloride inhibition of uPA mRNA levels. Transcriptional elongation experiments using isolated nuclei indicated that while the induction effects of PMA or CHX on uPA gene expression were mediated at the post-transcriptional level, amiloride acted at both transcription and post-transcription levels. The inhibitory effects of amiloride on uPA gene expression reported in this paper may offer the prospect of developing new therapeutic approaches to the prevention of invasion and metastasis by adenocarcinomas.

Amiloride↗
PubMed1994

Human urokinase receptor expression is inhibited by amiloride and induced by tumor necrosis factor and phorbol ester in colon cancer cells.

The modulation of urokinase plasminogen activator receptor (uPAR) gene expression by tumor necrosis factor alpha (TNF alpha), phorbol ester (PMA) and amiloride was studied in three colon cancer cell lines. uPAR mRNA and protein were induced by TNF alpha and by PMA but were inhibited by amiloride at concentrations of 0.1 to 1 mM in the presence or absence of TNF alpha and PMA. Nuclear run-on transcription assay indicated that the effects of amiloride and TNF alpha were mediated at least in part at the transcriptional level, whereas PMA may act in part via a posttranscriptional mechanism. These results suggested that uPAR gene expression is modulated by multiple signal transduction pathways.

Amiloride↗
PubMed1994

Morphological and acoustical analysis of the nasal and the paranasal cavities.

Morphological measurements of the nasal and paranasal cavities were conducted to investigate their relevance to the acoustic properties of the human nasal tract. The magnetic resonance imaging (MRI) technique was used to measure the three-dimensional geometry of the vocal tract. The area function of the nasal tract was calculated for seven subjects based on data obtained during natural breathing. The entire vocal tract was measured for five subjects during sustained production of nasal consonants. A marked morphological difference was observed between our data and previously published data [A. S. House and K. N. Stevens, J. Speech Hear. Disord. 21, 218-232 (1956); G. Fant, Acoustic Theory of Speech Production (Mouton, The Hague, 1970), 2nd ed., p. 139] particularly in the middle portion of the nasal tract. Previous data derived from cadaver specimens showed a large cavity in the middle portion possibly due to an absent or dehydrated mucous membrane, while our data showed narrow passages due to thickly layered mucosa. It has been confirmed by an additional experiment that the wide cavity is reproducible by applying an adrenergic agent to the nasal mucosa. Transfer functions of the vocal tract and the nasal tract were calculated from measured data, and compared to spectra of real speech signals recorded subsequent to the MRI experiment. The results indicate that asymmetry between the two nasal passages can cause extra pole-zero pairs, and suggest that the paranasal cavities play an important role in shaping the spectral characteristics of human nasal sounds.

Adult↗
PubMed1989

Influence of hospitalization on drug therapy in the elderly.

In order to determine whether acute hospitalization leads to changes in the medications used by the elderly after discharge, we studied the medications used at admission and discharge for 197 elderly subjects admitted to one hospital. We found that 40% of all admission medications were discontinued by discharge and 45% of all discharge medications were newly started during the hospitalization. Although the number of drugs used did not increase significantly from admission to discharge (4.50 to 4.80, P = .128), the number of narcotics, laxatives, and antibiotics increased significantly. For those elderly subjects admitted to the hospital taking less than the average number of medications, the overall use of medication increased from admission to discharge (2.89 to 3.75, P less than .0001). These "low users" were discharged on more benzodiazepines, narcotics, laxatives, antibiotics, and cardiac medications. Our data suggest that during hospitalization admission medications are discontinued and new medications are started in large numbers and that these changes are accompanied by a tendency towards the increased use of certain categories of medications. These changes may place the elderly patient at increased risk of polypharmacy and its complications.

Aged↗
PubMed1987

Intralysosomal hydrolysis of thyroglobulin: specific and cAMP-mediated activation by TSH.

Pig thyroid slices, pre-labelled with [125I]iodide, were incubated with or without thyrotropin (TSH), dibutyryl cyclic AMP (dbcAMP) or forskolin. After lysosome isolation, intralysosomal thyroglobulin (Tg) hydrolysis was determined by the increment in trichloroacetic acid (TCA)-soluble radioactivity. TSH stimulated the intralysosomal Tg hydrolysis. This stimulation was time and concentration dependent and was mimicked by forskolin or dbcAMP. When endocytosis and protein synthesis were blocked by inhibitors (nocodazole and puromycin) the stimulatory effect was still maintained. We conclude that TSH increases quickly and specifically, via a cAMP-mediated process, intralysosomal Tg hydrolysis, independent of its effects on endocytosis of Tg and lysosomal protease synthesis.

1-Methyl-3-isobutylxanthine↗