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Biomedical subjects

J Chang

Publications and source records attributed to J Chang.

At least 55 records · Page 3Linked to original sources

Measurement of single electrons and implications for charm production in Au+Au collisions at square root[s(NN)] = 130 GeV.

Transverse momentum spectra of electrons from Au+Au collisions at square root[s(NN)] = 130 GeV have been measured at midrapidity by the PHENIX experiment at the Relativistic Heavy Ion Collider. The spectra show an excess above the background from photon conversions and light hadron decays. The electron signal is consistent with that expected from semileptonic decays of charm. The yield of the electron signal dN(e)/dy for p(T) > 0.8 GeV/c is 0.025+/-0.004(stat)+/-0.010(syst) in central collisions, and the corresponding charm cross section is 380+/-60(stat)+/-200(syst) microb per binary nucleon-nucleon collision.

Journal Article↗

H. pylori infection and genotyping in patients undergoing upper endoscopy at inner city hospitals.

Kings County Hospital (KCH), and St. John's Episcopal Hospital (SJH) are inner-city hospitals in New York City serving predominantly minority populations. Staten Island University Hospital (SIUH) serves a predominantly middle-class Caucasian population. We examined H. pylori (HP) infection in patients undergoing upper endoscopy at these hospitals. Two gastric biopsies were obtained from each patient. One biopsy was examined by histology or the rapid urease test for the presence of HP. The other was subjected to analysis by PCR to detect HP DNA and to identify putative HP virulence factors. Of 200 subjects, 54% were African-American, 10% were Hispanic, and 36% were Caucasian. HP infection rates in African-American, Hispanic, and Caucasian patients were 43%, 20%, and 11%, respectively. Many of the African-American patients are recent immigrants from the Caribbean Islands. In these patients, an inverse relationship was observed between HP infection and the number of years living in the United States. Higher levels of HP infection were observed in patients with duodenitis and peptic ulcer disease. With respect to HP virulence factors, the vacA s1b and m1 alleles, as well as the iceA2 allele were the predominant alleles expressed in HP-positive samples obtained from African-Americans. The cagA gene was detected in 81% of HP-positive samples. However, CagA positivity was not related to any specific gastrointestinal disorder. Our findings indicate that among several ethnic groups served by three hospitals, African-American patients have the highest rate of HP infection. Moreover, in AfricanAmerican patients undergoing endoscopy: (1) HP infection was inversely related to the number of years the patients have been living in the USA; (2) HP infection rates were higher in patients diagnosed with duodenitis and peptic ulcer disease versus other disorders; (3) expression of the CagA gene was not associated with any specific gastroduodenal disorder; and (4) there was little allelic heterogeneity with respect to VacA and IceA subtypes. These findings suggest that inner-city African-Americans are more likely to be infected with HP and suffer from more serious gastroduodenal disorders than other ethnic groups.

Black or African American↗

Simultaneous toe-to-hand transfer and lower extremity amputations for severe upper and lower limb defects: the use of spare parts.

From 1995 to 2000, five microvascular toe-to-hand transfers were performed in three children who were simultaneously undergoing lower extremity amputations. Their ages at time of transfer ranged from 4 to 10 years and the types of lower extremity amputation included toe amputation, foot amputation and through-knee amputation. The resulting toe-to-hand transfers included three great toe-to-thumb transfers and one combined great and second toe-to-hand transfer. The toe-to-hand transfers were all successful and all the lower extremity amputations healed without complications. In all cases, improved hand function and lower extremity function was noted by the families. These unique cases represent the ultimate use of spare parts in congenital hand surgery.

Amputation, Surgical↗

Cone-beam CT with megavoltage beams and an amorphous silicon electronic portal imaging device: potential for verification of radiotherapy of lung cancer.

We investigate the potential of megavoltage (MV) cone-beam CT with an amorphous silicon electronic portal imaging device (EPID) as a tool for patient position verification and tumor/organ motion studies in radiation treatment of lung tumors. We acquire 25 to 200 projection images using a 22 x 29 cm EPID. The acquisition is automatic and requires 7 minutes for 100 projections; it can be synchronized with respiratory gating. From these images, volumetric reconstruction is accomplished with a filtered backprojection in the cone-beam geometry. Several important prereconstruction image corrections, such as detector sag, must be applied. Tests with a contrast phantom indicate that differences in electron density of 2% can be detected with 100 projections, 200 cGy total dose. The contrast-to-noise ratio improves as the number of projections is increased. With 50 projections (100 cGy), high contrast objects are visible, and as few as 25 projections yield images with discernible features. We identify a technique of acquiring projection images with conformal beam apertures, shaped by a multileaf collimator, to reduce the dose to surrounding normal tissue. Tests of this technique on an anthropomorphic phantom demonstrate that a gross tumor volume in the lung can be accurately localized in three dimensions with scans using 88 monitor units. As such, conformal megavoltage cone-beam CT can provide three-dimensional imaging of lung tumors and may be used, for example, in verifying respiratory gated treatments.

Algorithms↗

Suppression of hadrons with large transverse momentum in central Au+Au collisions at root square[s(NN)] = 130 GeV.

Transverse momentum spectra for charged hadrons and for neutral pions in the range 1 GeV/c<p(T)<5 GeV/c have been measured by the PHENIX experiment at RHIC in Au+Au collisions at root square[s(NN)] = 130 GeV. At high p(T) the spectra from peripheral nuclear collisions are consistent with scaling the spectra from p+p collisions by the average number of binary nucleon-nucleon collisions. The spectra from central collisions are significantly suppressed when compared to the binary-scaled p+p expectation, and also when compared to similarly binary-scaled peripheral collisions, indicating a novel nuclear-medium effect in central nuclear collisions at RHIC energies.

Journal Article↗

Antilambda production in Au+Au collisions at 11.7A GeV/c.

We present results for antilambda and antiproton production in Au+Au collisions at 11.7 A GeV/c including spectra and extracted invariant yields for both species in central and peripheral collisions in the rapidity range 1.0<y<1.4. The antilambda yield increases from dN(Lambda;)/dy = 1.2(+0.7+0.2)(-0.6-0.2)x10(-3) in peripheral collisions to 19(+4+3)(-5-2)x10(-3) in central collisions. The direct antiproton yield is deduced from the measured total antiproton spectra to extract the ratio of antilambda-to-direct-antiproton production. The Lambda/p ratio near midrapidity increases from 0.26(+0.19+0.5)(-0.15-0.4) in peripheral collisions to 3.6(+4.7+2.7)(-1.8-1.1) in central collisions, a value larger than current theoretical estimates.

Journal Article↗

Visualization and characterization of respiratory syncytial virus F-specific CD8(+) T cells during experimental virus infection.

CTL play a major role in the clearance of respiratory syncytial virus (RSV) during experimental pulmonary infection. The fusion (F) glycoprotein of RSV is a protective Ag that elicits CTL and Ab response against RSV infection in BALB/c mice. We used the strategy of screening a panel of overlapping synthetic peptides corresponding to the RSV F protein and identified an immunodominant H-2K(d)-restricted epitope (F(85-93); KYKNAVTEL) recognized by CD8(+) T cells from BALB/c mice. We enumerated the F-specific CD8(+) T cell response in the lungs of infected mice by flow cytometry using tetramer staining and intracellular cytokine synthesis. During primary infection, F(85-93)-specific effector CD8(+) T cells constitute approximately 4.8% of pulmonary CD8(+) T cells at the peak of the primary response (day 8), whereas matrix 2-specific CD8(+) T cells constituted approximately 50% of the responding CD8(+) T cell population in the lungs. When RSV F-immune mice undergo a challenge RSV infection, the F-specific CD8(+) T cell response is accelerated and dominates, whereas the primary response to the matrix 2 epitope in the lungs is reduced by approximately 20-fold. In addition, we found that activated F-specific effector CD8(+) T cells isolated from the lungs of RSV-infected mice exhibited a lower than expected frequency of IFN-gamma-producing CD8(+) T cells and were significantly impaired in ex vivo cytolytic activity compared with competent F-specific effector CD8(+) T cells generated in vitro. The significance of these results for the regulation of the CD8(+) T cell response to RSV is discussed.

Animals↗

Residues Y179 and H101 of a hydrophobic patch of factor VII are involved in activation by factor Xa.

We studied factor Xa activation of human factor VII in hopes of identifying factor VII residues, not adjacent to the cleavage site, involved in this interaction. We made eight factor VIIs with single mutations (N100A, H101A, D102Q, L144A, R147A, Y179A, D186A, and F256A) and two factor VIIs with multiple mutations [MM3 (L144A/R147A/D186A) and MM4 (N100A/H101A/Y179A/F256A)]. Residues in MM3 have previously been identified as affecting factor X activation, and the residues of MM4 are located at a hydrophobic patch of factor VII on the opposite side of the catalytic domain from those in MM3. Only H101A, Y179A, and MM4 were activated significantly more slowly than the wild type. Results of our kinetic analyses showed that the catalytic efficiency of factor Xa for activation of factor VII was 176- and 234-fold higher than that for H101A andY179A, respectively. All the mutants with measurable activity had affinities for tissue factor similar to those of the wild type. The activated hydrophobic patch residues, except N100A, which is adjacent to one of the catalytic residues, had normal activities toward both a small peptide substrate and factor X. The rest of the activated mutants (except D102Q with no activity) had reduced activities toward the small substrate (except R147A) and factor X. We conclude that factor VII activation by factor Xa and factor VIIa's catalytic interaction with factor X involve different regions in the catalytic domain, and residues H101 and Y179, part of an aromatic hydrophobic patch, are specifically involved in factor Xa activation of factor VII.

Amino Acid Sequence↗

Methodology for miniaturized CE and insulation on a silicon substrate.

We have developed a synchronously switched cyclic capillary electrophoresis (CE) separator that is fabricated on a silicon substrate and glass. Au electrodes were also integrated on the chip that could be wire bonded to the printed circuit board (PCB). The advantage of using a cyclic separator is that it has the high resolution and the ability to separate each sample to the designated reservoir from mixed samples. This approach makes it possible to reduce the supplied voltage and the total chip size. Another goal of this work was to introduce the methodology of electroosmotic flow (EOF) on the silicon substrate and to separate DNA samples using a modified double-T injector.

Journal Article↗

Altering telomere structure allows telomerase to act in yeast lacking ATM kinases.

BACKGROUND: Telomerase is a ribonucleoprotein that copies a short RNA template into telomeric DNA, maintaining eukaryotic chromosome ends and preventing replicative senescence. Telomeres differentiate chromosome ends from DNA double-stranded breaks. Nevertheless, the DNA damage-responsive ATM kinases Tel1p and Mec1p are required for normal telomere maintenance in Saccharomyces cerevisiae. We tested whether the ATM kinases are required for telomerase enzyme activity or whether it is their action on the telomere that allows telomeric DNA synthesis. RESULTS: Cells lacking Tel1p and Mec1p had wild-type levels of telomerase activity in vitro. Furthermore, altering telomere structure in three different ways showed that telomerase can function in ATM kinase-deleted cells: tel1 mec1 cells senesced more slowly than tel1 mec1 cells that also lacked TLC1, which encodes telomerase RNA, suggesting that tel1 mec1 cells have residual telomerase function; deleting the telomere-associated proteins Rif1p and Rif2p in tel1 mec1 cells prevented senescence; we isolated a point mutation in the telomerase RNA template domain (tlc1-476A) that altered telomeric DNA sequences, causing uncontrolled telomeric DNA elongation and increasing single strandedness. In tel1 mec1 cells, tlc1-476A telomerase was also capable of uncontrolled synthesis, but only after telomeres had shortened for >30 generations. CONCLUSION: Our results show that, without Tel1p and Mec1p, telomerase is still active and can act in vivo when the telomere structure is disrupted by various means. Hence, a primary function of the ATM-family kinases in telomere maintenance is to act on the substrate of telomerase, the telomere, rather than to activate the enzymatic activity of telomerase.

Ataxia Telangiectasia Mutated Proteins↗

Measurement of the midrapidity transverse energy distribution from square root of [(s)NN] = 130 GeV Au + Au collisions at RHIC.

The first measurement of energy produced transverse to the beam direction at the Relativistic Heavy-Ion Collider at Brookhaven National Laboratory is presented. The midrapidity transverse energy density per participating nucleon rises steadily with the number of participants, closely paralleling the rise in charged-particle density, such that / remains relatively constant as a function of centrality. The energy density calculated via Bjorken's prescription for the 2% most central Au+Au collisions at square root[s(NN)] = 130 GeV is at least epsilon(Bj) = 4.6 GeV/fm(3), which is a factor of 1.6 larger than found at sqrt[s(NN)] = 17.2 GeV ( Pb+Pb at CERN).

Journal Article↗

Activation of heat-shock factor by stretch-activated channels in rat hearts.

BACKGROUND: Previously, we have observed that the isolated, erythrocyte-perfused rabbit heart has increased levels of heat-shock protein (HSP) 72 after a mild mechanical stress. We hypothesized that stretch-activated ion channels (SACs) mediated this increase. Methods and Results-- To test this hypothesis, we subjected isolated, perfused rat hearts to mechanical stretch. Gel mobility shift assay showed that heat-shock factor (HSF) was activated in hearts with mechanical stretch, but not in controls. Supershift experiments demonstrated that HSF1 was the transcription factor. Northern blots revealed the concomitant increase in HSP72 mRNA in stretched rat hearts. In a separate set of experiments, gadolinium, an inhibitor of SACs, was added to the perfusate. Gadolinium inhibited the activation of HSF and decreased HSP72 mRNA level. Because gadolinium can inhibit both SACs and L-type calcium channels, we perfused a group of hearts with diltiazem, a specific L-type calcium channel blocker, to eliminate the involvement of L-type calcium channels. Diltiazem failed to inhibit the activation of HSF. CONCLUSIONS: Stretch in the rat heart results in activation of HSF1 and an increase in HSP72 mRNA through SACs. This represents a novel mechanism of HSF activation and may be an important cardiac signaling pathway for hemodynamic stress.

Animals↗

Anisotropic elastic interactions of a periodic dislocation array.

A method for calculating the anisotropic elastic energy of a dislocation dipole in a periodic cell is derived in which the infinite image summation is absolutely convergent. The core energy of a screw dislocation in Si, extracted from atomistic simulation, is shown to be manifestly system size invariant. Existence of special cell geometry where complete cancellation of elastic interactions occurs is demonstrated.

Journal Article↗

Expression of the Oct-1 transcription factor and characterization of its interactions with the Bob1 coactivator.

The Oct-1 transcription factor regulates a variety of tissue-specific and general housekeeping genes by recruiting specialized coactivators of transcription. It acts synergistically with the B-cell-specific coactivator Bob1 (OCA-B, OBF-1) to stimulate transcription of immunoglobulin genes. To analyze Oct-1's interactions with Bob1 and other regulatory proteins, we have overexpressed and purified different functional domains of the recombinant proteins. A version of Oct-1 that encompasses the amino-terminal activation region and the POU DNA-binding domain was extensively characterized (OctDeltaC1; comprising residues 1-445). Using an in vitro transcription assay, we demonstrate that this fragment is sufficient and necessary to stimulate transcription from an immunoglobulin promoter with Bob1. It also coactivates from the herpes simplex virus ICPO promoter element in the presence of VP16. Using a range of spectroscopic and biophysical techniques, we demonstrate that the activation domains of Oct-1 and Bob1 have little globular structure and that they do not physically interact. Thus, their functional synergy is likely to arise by the co-recruitment of common factors as part of a larger regulatory assembly. We propose a hypothesis to explain why the activation domains of these and other transcription factors of metazoans have little if any intrinsic structure.

Amino Acid Sequence↗

National trends in condom use among at-risk heterosexuals in the united states.

Based on national level surveys, we examined data relevant to the United States' overall effort to prevent the spread of HIV among heterosexual adults. We examined changes in condom use among at-risk heterosexuals over the past decade. The observed increases over time in condom use across all heterosexual at-risk population segments are consistent with the observed (declines) trends in HIV and syphilis in the 1990s. These results and findings from prior studies suggest that U.S. efforts to facilitate condom use and contain HIV and related sexually transmitted disease (STD)-cofactors among adult at risk heterosexuals was succeeding over most of the 1990s. The absence of national level behavioral trend data after 1996, and the ambiguities of HIV spread suggest some caution in projecting trends into this century. National and local efforts need to be directed at sustaining behavioral change and conducting more rigorous studies on population trends in HIV/STD-related behaviors/pathogens.

Adolescent↗

Modulation of C-reactive protein-mediated monocyte chemoattractant protein-1 induction in human endothelial cells by anti-atherosclerosis drugs.

BACKGROUND: C-reactive protein (CRP) induces adhesion molecule expression by endothelial cells. However, the effects of CRP on chemokine expression by endothelial cells are not known. METHODS AND RESULTS: We tested the effects of CRP on the production of the chemokines monocyte chemoattractant protein-1 (MCP-1) and RANTES in cultured human umbilical vein endothelial cells. The secretion of chemokines was assessed by ELISA. Incubation with 100 microgram/mL recombinant human CRP induced a 7-fold increase in MCP-1 but no change in RANTES secretion. We showed that the effect of CRP on MCP-1 was present even at 5 microgram/mL CRP, with stepwise increases as the CRP concentration was increased to 10, 50, and 100 microgram/mL. The effect of CRP on MCP-1 induction was not influenced by aspirin (at concentrations up to 1 mmol/L), but it was significantly inhibited by 5 micromol/L simvastatin. The peroxisome proliferator-activated receptor-alpha activators fenofibrate (100 micromol/L) and Wy-14649 (100 micromol/L) almost completely abolished the induction of MCP-1, but the peroxisome proliferator-activated receptor-gamma activator ciglitazone had only a moderate effect. CONCLUSIONS: These results further strengthen the role of CRP in the pathogenesis of vascular inflammation and, likely, atherosclerosis and provide a crucial insight into a novel mechanism of action of anti-atherosclerosis drugs such as simvastatin and fenofibrate.

C-Reactive Protein↗

Centrality dependence of charged particle multiplicity in Au-Au collisions at square root of (s)NN = 130 GeV.

We present results for the charged-particle multiplicity distribution at midrapidity in Au-Au collisions at square root of [s(NN)] = 130 GeV measured with the PHENIX detector at RHIC. For the 5% most central collisions we find dN(ch)/d eta(vertical line eta = 0) = 622+/-1(stat)+/-41(syst). The results, analyzed as a function of centrality, show a steady rise of the particle density per participating nucleon with centrality.

Journal Article↗