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Biomedical subjects

M Pang

Publications and source records attributed to M Pang.

At least 19 recordsLinked to original sources

Human histologic and electromicroscopic analysis with synthetic peptide enhanced hydroxyapatite in the maxillary sinus elevation procedure: a case report.

Elevation of the sinus floor to augment the alveolar process to place implants is an effective treatment. The traditional use of autologous bone implies a secondary donor site and the related morbidity, and, hence, is not readily accepted by many patients. The new graft material, synthetic peptide enhanced hydroxyapatite (PepGen P-15 Flow, Ceramed Dental, Lakewood, CO, DENTSPLY Int.,York, PA), shows the ease in use and ability to generate new bone growth in the sinus elevation procedure. Histologic and electromicroscopic analysis was performed on the new bone formed after the application.

Aged↗

Galectin-1 induces nuclear translocation of endonuclease G in caspase- and cytochrome c-independent T cell death.

Galectin-1, a mammalian lectin expressed in many tissues, induces death of diverse cell types, including lymphocytes and tumor cells. The galectin-1 T cell death pathway is novel and distinct from other death pathways, including those initiated by Fas and corticosteroids. We have found that galectin-1 binding to human T cell lines triggered rapid translocation of endonuclease G from mitochondria to nuclei. However, endonuclease G nuclear translocation occurred without cytochrome c release from mitochondria, without nuclear translocation of apoptosis-inducing factor, and prior to loss of mitochondrial membrane potential. Galectin-1 treatment did not result in caspase activation, nor was death blocked by caspase inhibitors. However, galectin-1 cell death was inhibited by intracellular expression of galectin-3, and galectin-3 expression inhibited the eventual loss of mitochondrial membrane potential. Galectin-1-induced cell death proceeds via a caspase-independent pathway that involves a unique pattern of mitochondrial events, and different galectin family members can coordinately regulate susceptibility to cell death.

Active Transport, Cell Nucleus↗

A cumulative experience examining the effect of natural and synthetic antimicrobial peptides vs. Chlamydia trachomatis.

We tested the activity of 48 structurally diverse antimicrobial peptides against Chlamydia trachomatis, serovar L2. The peptides' activity against C. trachomatis, serovar L2 was measured in 48-h McCoy cell shell vial assays. Peptides of 16-20 amino acids were more active than larger peptides, such as defensins. Beta-sheet protegrins, as well as alpha-helical peptides such as novispirin (G-10) were equally active. Enantiomers were as active as native structures. Moderate-sized circular mini-defensins were less effective against C. trachomatis. Moderate-sized cationic peptides may be useful in microbicide preparations designed to prevent chlamydial infection.

Amino Acid Sequence↗

Activity of Novispirin G-10, a novel antimicrobial peptide against Chlamydia trachomatis and vaginosis-associated bacteria.

We tested the activity of Novispirin G-10, a novel antimicrobial alpha-helical octadecapeptide structurally related to cathelicidins and other innate immunity peptides, against Chlamydia trachomatis serovars L2, D, and E and three organisms associated with bacterial vaginosis (BV). The peptide's activity against C. trachomatis was measured in 48-h shell vial assays with McCoy cell targets. Exposure to 100 micro g/ml of Novispirin G-10 reduced the infectivity of serovars D and E by 99.4-100% and serovar L2 by 91.7-99.1%. At the same concentration of 100 micro g/ml, Novispirin G-10 rapidly killed >99% of Mobiluncus curtisii, Gardnerella vaginalis, and Prevotella bivia, in standard colony-forming unit (CFU) assays. Given its simple structure and relative lack of cytotoxic and hemolytic activity, Novispirin G-10 may be a useful component of microbicide preparations designed to prevent chlamydial infection and/or remediate the abnormal vaginal flora associated with BV.

Anti-Bacterial Agents↗

Measurement of the K(L) charge asymmetry.

We present a measurement of the charge asymmetry delta(L) in the mode K(L)-->pi(+/-)e(-/+)nu based on 298 x 10(6) analyzed decays. We measure a value of delta(L) = [3322+/-58(stat)+/-47(syst)]x10(-6), in good agreement with previous measurements and 2.4 times more precise than the current best published result. The result is used to place more stringent limits on CPT and DeltaS = DeltaQ violation in the neutral kaon system.

Journal Article↗

Defective expression and tyrosine phosphorylation of the T cell receptor zeta chain in peripheral blood T cells from systemic lupus erythematosus patients.

We have reported that tyrosine phosphorylation and expression of the T cell receptor zeta chain (TCR zeta) was decreased in two systemic lupus erythematosus (SLE) patients with an abnormal TCR zeta lacking exon-7. To examine further the TCR zeta defect and any possible relationship with specific clinical features, we studied the expression of TCR zeta in peripheral blood T cells from 44 patients with SLE, 53 with other rheumatic diseases (30 rheumatoid arthritis (RA), 11 systemic sclerosis (SSc) and 12 primary Sjögren's syndrome(SjS)) and 39 healthy individuals. Flow cytometric analysis demonstrated a significant decrease in the expression of TCR zeta in SLE (P < 0.001), but not in the other rheumatic diseases. Immunoprecipitation experiments confirmed that the expression of TCR zeta in SLE T cells was decreased dramatically (normal: 111.4 +/- 22.6%, SLE: 51.6 +/- 37.4%, P < 0.0001). The decrease in TCR zeta did not correlate with disease activity, or with the dose of prednisolone (PSL). There were, however, three SLE patients in whom the level of TCR zeta expression normalized after treatment, suggesting that mechanisms responsible for the TCR zeta defect appear to be heterogeneous. These results confirm the defective expression and altered tyrosine phosphorylation of TCR zeta in a large proportion of SLE patients, suggesting that it may play an important role in T cell dysfunction in SLE.

Adult↗

Substituted imidazoles as glucagon receptor antagonists.

A modestly active, nonselective triarylimidazole lead was optimized for binding affinity with the human glucagon receptor. This led to the identification of a 2- and/or 4-alkyl or alkyloxy substituent on the imidazole C4-aryl group as a structural determinant for significant enhancement in binding with the glucagon receptor (e.g., 41, IC(50)=0.053 microM) and selectivity (>1000x) over p38MAP kinase in this class of compounds.

Animals↗

First measurement of form factors of the decay Xi(0) --> Sigma(+)e(-)nu macro(e).

We present the first measurement of the form factor ratios g(1)/f(1) (direct axial vector to vector), g(2)/f(1) (second class current), and f(2)/f(1) (weak magnetism) for the decay Xi(0)-->Sigma(+)e(-)nu macro(e) using the KTeV (E799) beam line and detector at Fermilab. From the Sigma(+) polarization measured with the decay Sigma(+)-->p pi(0) and the e(-)-nu; correlation, we measure g(1)/f(1) to be 1.32+/-(0.21)(0.17)(stat)+/-0.05(syst), assuming the SU(3)(f) (flavor) values for g(2)/f(1) and f(2)/f(1). Our results are all consistent with exact SU(3)(f) symmetry.

Journal Article↗

Branching ratio measurement of the decay K(L) --> e(+)e(-)mu(+)mu(-).

We have collected a 43 event sample of the decay K(L)-->e(+)e(-)mu(+)mu(-) with negligible backgrounds and measured its branching ratio to be (2.62+/-0.40+/-0.17)x10(-9). We see no evidence for CP violation in this decay. In addition, we set the 90% confidence upper limit on the combined branching ratios for the lepton flavor violating decays K(L)-->e(+/-)e(+/-)mu(-/+)mu(-/+) at B(K(L)-->e(+/-)e(+/-)mu(-/+)mu(-/+))< or =1.23x10(-10), assuming a uniform phase space distribution.

Journal Article↗

Measurement of the branching ratio and form factor of K(L)-->mu(+)mu(-)gamma.

We report on the analysis of the rare decay K(L)-->mu(+)mu(-)gamma the 1997 data from the KTeV experiment at Fermilab. A total of 9327 candidate events are observed with 2.4% background, representing a factor of 40 increase in statistics over the current world sample. We find that B(K(L)-->mu(+)mu(-)gamma) = (3.62 +/- 0.04(stat) +/- 0.08(syst)) x 10(-7). The form factor parameter alpha(K*) is measured to be alpha(K*) = -0.160(+0.026)(-0.028). In addition, we make the first measurement of the parameter alpha from the D'Ambrosio-Isidori-Portolés form factor, finding alpha = -1.54 +/- 0.10. In that model, this alpha measurement limits the Cabibbo-Kobayashi-Maskawa parameter rho>-0.2.

Journal Article↗

Measurements of the rare decay K(L) --> e(+)e(-)e(+)e(-).

We observe 441 K(L)-->e(+)e(-)e(+)e(-) candidate events with a background of 4.2 events and measure B(K(L)-->e(+)e(-)e(+)e(-)) = [3.72+/-0.18(stat)+/-0.23(syst)]x10(-8) in the KTeV/E799II experiment at Fermilab. Using the distribution of the angle between the planes of the e(+)e(-) pairs, we measure the CP parameters beta(CP) = -0.23+/-0.09(stat)+/-0.02(syst) and gamma(CP) = -0.09+/-0.09(stat)+/-0.02(syst). We also present the first detailed study of the e(+)e(-) invariant mass spectrum in this decay mode.

Journal Article↗

Measurement of the branching ratio and asymmetry of the decay Xi degrees -->Sigma degrees gamma.

We have studied the rare weak radiative hyperon decay Xi degrees -->Sigma degrees gamma in the KTeV experiment at Fermilab. We have identified 4045 signal events over a background of 804 events. The dominant Xi degrees -->Lambdapi degrees decay, which was used for normalization, is the only important background source. An analysis of the acceptance of both modes yields a branching ratio of B(Xi degrees -->Sigma degrees gamma)/B(Xi degrees -->Lambdapi degrees ) = (3.34+/-0.05+/-0.09)x10(-3). By analyzing the final state decay distributions, we have also determined that the Sigma degrees emission asymmetry parameter for this decay is alpha(XiSigma) = -0.63+/-0.09.

Journal Article↗

Study of the K(0)(L) --> pi(+)pi(-)gamma Direct Emission Vertex.

We have performed studies of the K(0)(L)-->pi(+)pi(-)gamma direct emission ( DE) and inner Bremsstrahlung ( IB) vertices, based on data collected by KTeV during the 1996 Fermilab fixed target run. We find a(1)/a(2) = -0.737+/-0.034 GeV2 for the DE form-factor parameter in the rho-propagator parametrization, and report on fits of the form factor to linear and quadratic functions as well. We concurrently measure gamma(K(0)(L)-->pi(+)pi(-)gamma,E(*)(gamma)>20 MeV)/gamma(K(0)(L)-->pi(+)pi(-)) = (20.8+/-0.3)x10(-3), and a K(0)(L)-->pi(+)pi(-)gamma DE/(DE+IB) branching ratio of 0.683+/-0.011.

Journal Article↗

Search for the decay KL --> pi(0)e+e-.

We report on a search for the decay KL-->pi(0)e+e- carried out by the KTeV/E799 experiment at Fermilab. This decay is expected to have a significant CP violating contribution and the measurement of its branching ratio could support the Cabibbo-Kobayashi-Maskawa mechanism for CP violation or could point to new physics. Two events were observed in the 1997 data with an expected background of 1.06+/-0.41 events, and we set an upper limit B(KL-->pi(0)e+e-)<5.1 x 10(-10) at the 90% confidence level.

Journal Article↗

A clinically relevant CTLA4-Ig-based regimen induces chimerism and tolerance to heart grafts.

BACKGROUND: We determined whether a nontoxic CTLA4-Ig-based conditioning regimen effected mixed chimerism and donor-specific tolerance when heart and bone marrow were transplanted simultaneously. METHODS: Fully mismatched rat strain combinations were used. Recipients received total-body irradiation (300 centigrays), bone marrow (10(8) cells), and cardiac transplants from the donor on day 0. Subsequently, recipient animals received CTLA4-Ig (2 mg/kg, every other day, x 5 doses), tacrolimus (1 mg/kg/day; days 0 to 9), and one dose (10 mg) of antilymphocyte serum on day 10. RESULTS: All bone marrow recipients (n = 7) developed mixed chimerism (mean = 25% +/- 9% at 1 year) and accepted cardiac allografts permanently (> 375 +/- 32 days). Recipients that received conditioning regimen but no bone marrow (n = 5) rejected donor hearts within 51 +/- 13 days (p < 0.01). Recipients that accepted heart grafts also permanently accepted (> 180 days) donor-specific skin grafts, but rapidly rejected (< 10 days) third-party skin grafts. CONCLUSIONS: A nontoxic CTLA4-Ig-based conditioning regimen effects mixed chimerism and donor-specific tolerance when heart and bone marrow are transplanted simultaneously. This regimen may have clinical application.

Abatacept↗

Combined host-conditioning with CTLA4-Ig, tacrolimus, anti-lymphocyte serum, and low-dose radiation leads to stable mixed hematopoietic chimerism.

The toxic dose of irradiation required to achieve stable mixed hematopoietic chimerism is the major limitation to its clinical application in transplantation and other nonmalignant conditions such as hemoglobinopathies. This study examines the additive effect of costimulatory blockage, to our previously described tacrolimus-based conditioning regimen, in further reducing the dose of total-body irradiation to achieve stable mixed chimerism in rats. Fully mismatched, 4- to 6-week-old ACI and Wistar Furth rats were used as donors and recipients, respectively. Recipients were administered CTLA4-Ig 2mg/kg/day (alternate days) in combination with tacrolimus 1 mg/kg/day (daily) from day 0 through day +10, anti-lymphocyte serum 10 mg at day +10 (single dose), and total-body irradiation ranging from 100-600 cGy, prior to bone marrow transplantation (day 0) with 100 x 10(6) of T-cell-depleted bone marrow cells. Levels of donor chimerism were determined over a period of 12 months. The short course of CTLA4-Ig, tacrolimus, and ALS led to dramatic engraftments at reduced doses of irradiation: 100% (5/5) and 93% (13/14) of the animals developed mixed chimerism at 400 cGy and 300 cGy, respectively. At 300 cGy, recipients exhibited durable, multilineage mixed chimerism at 365 days with donor cells ranging from 19-42% (mean 23.4%) with no evidence of graft-vs-host disease. These mixed chimeras exhibited in vitro (mixed lymphocyte reaction) and in vivo (skin grafts) donor-specific tolerance. This study suggests that addition of costimulatory blockade to a tacrolimus-based conditioning regimen reduces the dose of irradiation required to achieve stable multilineage chimerism in rats.

Abatacept↗

Human homologs of the Xenopus oocyte cortical granule lectin XL35.

The cDNAs encoding two human homologs of the Xenopus oocyte lectin, XL35, were isolated from a small intestine cDNA library and termed HL-1 and HL-2. The deduced amino acid sequence of each homolog is about 60% identical and 80% similar to that of XL35, and none of these sequences contains the C-type lectin motif, although it is known that XL35 requires calcium for ligand binding. By Northern analysis, HL-1 transcripts are present at relatively high levels in heart, small intestine, colon, thymus, ovary, and testis. HL-2 transcripts, by contrast, are expressed only in small intestine. Immunocytochemistry using a polyclonal antibody produced against XL35 shows HL-1 protein to be localized exclusively in endothelial cells in colon, thymus, liver, and other tissues. Primary cultures of human aortic endothelial cells are positive for HL-1 expression by immunoblotting and by PCR analysis, but several other human cell types are not. HL-1 and -2 are both encoded at chromosome 1q23, the same locus that encodes the selectins. XL35, HL-1 and -2, and another mouse homolog are members of a new family of proteins whose members most likely perform diverse functions.

Animals↗

Rapid detection of Mycobacterium tuberculosis in contaminated BACTEC 12B broth cultures by testing with Amplified Mycobacterium Tuberculosis Direct Test.

Contamination of broth cultures of acid-fast bacilli (AFB) by bacterial species other than Mycobacterium species frequently occurs. Many of these contaminated cultures require redecontamination and reincubation before the appropriate tests can be performed for identification, significantly affecting the turnaround time for reporting culture results. In this study, the Amplified Mycobacterium Tuberculosis Direct Test (MTD; Gen-Probe) was performed to detect the Mycobacterium tuberculosis complex (MTBC) in 125 BACTEC 12B broth cultures with positive growth indices. Among these, 41 grew non-AFB bacteria only, and all 41 were negative by the MTD. The remaining 84 bottles contained contaminated cultures that grew both AFB and other bacteria or yeasts. Repeat decontamination and reincubation of these specimens required a mean time of 13 days (range, 3 to 40 days). The MTD results were positive for 10 samples, 9 of which were MTBC culture positive and 1 of which grew Myobacterium celatum, a species known to cross-react in the MTD. All cultures growing other mycobacterial species were negative by the MTD. The results of this study demonstrate that the MTD is both sensitive and specific in detecting MTBC in contaminated broth cultures and that, when used selectively, the MTD can potentially rule in or out a diagnosis of MTBC as much as 12 days earlier than using nonamplified DNA probe testing alone can.

Bacterial Typing Techniques↗