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Biomedical subjects

H Cao

Publications and source records attributed to H Cao.

At least 19 recordsLinked to original sources
PubMed2026

[Aggressive B-cell lymphomas with MYC gene cluster amplification: a clinicopathological analysis of eight cases].

Objective: To investigate the clinicopathological characteristics, molecular genetics, treatments and prognosis of aggressive B-cell lymphomas (ABCL) with MYC gene cluster amplification. Methods: Eight cases of ABCL with MYC gene cluster amplification were collected, including 6 cases from the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China and 2 consultation cases from outside hospitals. The histomorphology, immunohistochemical profiles, and molecular genetic characteristics were analyzed. Clinical follow-up and literature review were also conducted. Results: Among the eight patients, six were male and two were female, with an age 71.5 (61.7, 74.2) years. All six in-house patients presented with abdominal pain at onset, without B symptoms. Most cases were classified as Ann Arbor stage Ⅲ-Ⅳ. Extranodal involvement occurred in 5 of the 6 in-house cases, primarily affecting the gastrointestinal tract (4/5). All initial bone marrow biopsies showed no evidence of lymphoma. One patient had a history of immunosuppression following renal transplantation. Two cases exhibited diffuse large B-cell lymphoma (DLBCL) morphology. The other six showed high-grade features, while three of them showed Burkitt lymphoma-like morphology. Except for one case of blastoid variant mantle cell lymphoma, the remaining six cases (6/7) displayed a germinal center B-cell phenotype. None of the in-house cases harbored bcl-2 or bcl-6 rearrangements as shown by fluorescence in situ hybridization. 11q alterations were identified in all but one consultation case, including gain/loss type in five cases and 11q gain in two. 11q telomere loss of heterozygosity by chromosomal microarray analysis was not detected in one of the two cases with 11q gain that was subject to the test. The duration of follow-up ranged from 5.9 to 55.5 months, with 5 patients alive at the end of the study. Conclusions: ABCL with MYC gene cluster amplification often presents high-grade morphology and gastrointestinal involvement, which strongly suggests the alteration of 11q. It seems to have a favorable prognosis.

Humans↗
PubMed2003

Immunogenicity of a recombinant human immunodeficiency virus (HIV)-canarypox vaccine in HIV-seronegative Ugandan volunteers: results of the HIV Network for Prevention Trials 007 Vaccine Study.

In the first preventative human immunodeficiency virus (HIV) vaccine study to be carried out in Africa, 40 HIV-seronegative Ugandan volunteers were randomly assigned to receive a canarypox vector containing HIV-1 clade B (env and gag-pro) antigens (ALVAC-HIV; n = 20), control vector containing the rabies virus glycoprotein G gene (n = 10), or saline placebo (n = 10). Cytotoxic T lymphocyte activity against target cells expressing clade A, B, and D antigens was assessed using standard chromium-release and confirmatory interferon-gamma enzyme-linked immunospot (ELISPOT) assays. Neutralizing antibody responses to cell line-adapted strains and primary isolates in all 3 clades were also tested. Twenty percent of vaccine recipients generated detectable cytolytic responses to either Gag or Env, and 45% had vaccine-induced HIV-specific CD8(+) T cell responses, as measured by the ELISPOT assay. In contrast, only 5% of the control group had vaccine-specific responses. Neutralizing antibodies against primary and laboratory-adapted HIV-1 clade B strains were seen in 10% and 15% of vaccine recipients, respectively, but responses against clades A and D were not detected. Although the immunogenicity of this clade B-based vaccine was low, ALVAC-HIV elicited CD8(+) T cell responses with detectable cross-activity against clade A and D antigens in a significant proportion of vaccine recipients.

AIDS Vaccines↗
PubMed2002

Probing localized states with spectrally resolved speckle techniques.

We have studied the spatial extent of localized states in random media using speckle correlation techniques. Optical gain is introduced to a local region of a random medium to induce lasing of the localized states. The far-field speckle pattern of laser emission from a localized state gives its spatial field correlation function at the surface of the random medium. The envelope of the spatial field correlation function decays exponentially with the transverse coordinate on the surface. The decay length is independent of the pumping rate and the excitation area. We demonstrate that localized states exist in a disordered system that does not reach the localization threshold.

Journal Article↗
PubMed2002

Random laser in one dimension.

We present an analytical approach to random lasing in a one-dimensional medium, consistent with transfer matrix numerical simulations. It is demonstrated that the lasing threshold is defined by transmission through the passive medium and thus depends exponentially on the size of the system. Lasing in the most efficient regime of strong three-dimensional localization of light is discussed. We argue that the lasing threshold should have anomalously strong fluctuations from probe to probe, in agreement with recent measurements.

Journal Article↗
PubMed2002

The large GTPase dynamin regulates actin comet formation and movement in living cells.

The large GTPase dynamin (Dyn2) has been demonstrated by us and others to interact with several different actin-binding proteins. To define how Dyn2 might participate in actin dynamics in livings cells we have expressed green fluorescent protein (GFP)-tagged Dyn2 in cultured cells and observed labeling of comet-like vesicles and macropinosomes. The comet structures progressed with a constant velocity and were reminiscent of actin comets associated with motile vesicles in cells expressing type I phosphatidylinositol phosphate 5-kinases. Based on these observations we sought to determine whether Dyn2 is an integral component of actin comets. Cells expressing type I phosphatidylinositol phosphate 5-kinase and Dyn2-GFP revealed a prominent colocalization of Dyn2 and actin in comet structures. Interestingly, comet formation and motility were normal in cells expressing wild-type Dyn2-GFP but altered markedly in Dyn2 mutant-expressing cells. Dyn2K44A-GFP mutant cells displayed a significant reduction in comet number, length, velocity, and efficiency of movement. In contrast, comets in cells expressing Dyn2DeltaPRD-GFP appeared dark and did not incorporate the mutant Dyn2 protein, indicating that the proline-rich domain (PRD) is required for Dyn2 recruitment. Further, these comets were significantly longer and slower than those in control cells. These findings demonstrate a role for Dyn2 in actin-based vesicle motility.

Actins↗
PubMed2002

Cardiomyopathy in congenital complete lipodystrophy.

Molecular genetic studies have pointed to a relationship between congenital lipodystrophy syndromes and some cardiac disorders. For instance, mutations in LMNA cause either lipodystrophy or cardiomyopathy, indicating that different mutations in the same gene can produce these clinical syndromes. The present authors describe a 10-year-old female with Berardinelli-Seip congenital complete lipodystrophy (MIM 606158) caused by homozygosity for a frameshift mutation in BSCL2. In addition to the typical attributes of complete lipodystrophy, this subject had hypertrophic cardiomyopathy diagnosed in the first year of her life; its progress has been followed with non-invasive imaging. The mechanism underlying the hypertrophic cardiomyopathy in complete lipodystrophy is unclear. It may result from a direct effect of the mutant gene or it might be secondary to the effects of hyperinsulinemia on cardiac development. The variability of the associated cardiomyopathy in patients with complete generalized lipodystrophy may be caused by differential effects of mutations in the same gene or of mutations in different genes which underlie the lipodystrophy phenotype.

Cardiomyopathies↗
PubMed2002

Magnitude and frequency of cytotoxic T-lymphocyte responses: identification of immunodominant regions of human immunodeficiency virus type 1 subtype C.

A systematic analysis of immune responses on a population level is critical for a human immunodeficiency virus type 1 (HIV-1) vaccine design. Our studies in Botswana on (i) molecular analysis of the HIV-1 subtype C (HIV-1C) epidemic, (ii) frequencies of major histocompatibility complex class I HLA types, and (iii) cytotoxic T-lymphocyte (CTL) responses in the course of natural infection allowed us to address HIV-1C-specific immune responses on a population level. We analyzed the magnitude and frequency of the gamma interferon ELISPOT-based CTL responses and translated them into normalized cumulative CTL responses. The introduction of population-based cumulative CTL responses reflected both (i) essentials of the predominant virus circulating locally in Botswana and (ii) specificities of the genetic background of the Botswana population, and it allowed the identification of immunodominant regions across the entire HIV-1C. The most robust and vigorous immune responses were found within the HIV-1C proteins Gag p24, Vpr, Tat, and Nef. In addition, moderately strong responses were scattered across Gag p24, Pol reverse transcriptase and integrase, Vif, Tat, Env gp120 and gp41, and Nef. Assuming that at least some of the immune responses are protective, these identified immunodominant regions could be utilized in designing an HIV vaccine candidate for the population of southern Africa. Targeting multiple immunodominant regions should improve the overall vaccine immunogenicity in the local population and minimize viral escape from immune recognition. Furthermore, the analysis of HIV-1C-specific immune responses on a population level represents a comprehensive systematic approach in HIV vaccine design and should be considered for other HIV-1 subtypes and/or different geographic areas.

Amino Acid Sequence↗
PubMed2001

A quorum sensing-associated virulence gene of Pseudomonas aeruginosa encodes a LysR-like transcription regulator with a unique self-regulatory mechanism.

The human opportunistic pathogen Pseudomonas aeruginosa strain PA14 infects both plants and animals. Previously, using plants to screen directly for P. aeruginosa virulence-attenuated mutants, we identified a locus, pho34B12, relevant in mammalian pathogenesis. Here, nonsense point mutations in the two opposing ORFs identified in the pho34B12 locus revealed that one of them, mvfR (multiple virulence factor Regulator), is able to control all of the phenotypes that mutant phoA34B12 displays. Both genetic and biochemical evidence demonstrate that the mvfR gene encodes a LysR-like transcriptional factor that positively regulates the production of elastase, phospholipase, and of the autoinducers, 3oxo-dodecanoyl homoserine lactone (PAI I) and 2-heptyl-3-hydroxy-4-quinolone (PQS), as well as the expression of the phnAB operon, involved in phenazine biosynthesis. We demonstrate that the MvfR protein is membrane-associated and acts as a transcriptional activator until cells reach stationary phase, when a unique negative feedback mechanism is activated to signal the down-regulation of the MvfR protein. This work reveals an unprecedented virulence mechanism of P. aeruginosa and identifies a unique indispensable player in the P. aeruginosa quorum-sensing cascade.

Animals↗
PubMed2001

Model for a random laser.

The laser action in random media is studied numerically for a planar system of resonant scatterers pumped by an external laser. The eigenmodes of the finite system (quasistates) are "lossy" in the absence of gain because of the leakage of light outside the medium and can be characterized by their decay rates. Lasing occurs when the gain compensates the decay rate of the quasistate with the longest lifetime. The dependence of the lasing threshold on the number of scatterers (size of the system) is found to be I varies with 1/square root of (N), which agrees with recent experiments. We demonstrate that this dependence is strongly related to the fluctuations of quasistate decay rates and discuss the nature of these fluctuations.

Journal Article↗
PubMed2001

Decreased sensitivity of tristetraprolin-deficient cells to p38 inhibitors suggests the involvement of tristetraprolin in the p38 signaling pathway.

Treatment of macrophages with pyridinyl imidazole inhibitors of p38 protein kinases can inhibit lipopolysaccharide-stimulated tumor necrosis factor alpha secretion. However, bone marrow-derived macrophages from tristetraprolin (TTP)-deficient mice were less sensitive than normal macrophages to this effect of p38 inhibitors, despite evidence for normal p38 activation in response to lipopolysaccharide. TTP is known to cause decreased stability of tumor necrosis factor alpha and granulocyte-macrophage colony-stimulating factor mRNAs after binding to an AU-rich element in their 3'-untranslated regions. A recombinant TTP fusion protein could be phosphorylated by a recombinant p38 kinase in cell-free assays and was phosphorylated to the same extent by immunoprecipitated p38 derived from normal and TTP-deficient cells stimulated with lipopolysaccharide; in both cases, the enzyme activity was inhibited by the p38 inhibitors. TTP phosphorylation also was increased in intact macrophages after lipopolysaccharide stimulation, an effect that was blocked by the p38 inhibitors. Finally, TTP in mammalian cell extracts bound less well to an AU-rich element RNA probe than did the same amount of TTP following dephosphorylation. These results suggest that TTP may be a component of the signaling cascade, initiated by inflammatory stimuli and mediated in part by activation of p38, that ultimately leads to enhanced secretion of tumor necrosis factor alpha.

3' Untranslated Regions↗
PubMed2001

Robust HIV type 2 cellular immune response measured by a modified anthrax toxin-based enzyme-linked immunospot assay.

Evaluation of immune mechanisms responsible for control of viral replication is critical to understanding HIV-2 attenuated biological characteristics in pathogenesis and transmission. Evaluation of the cellular immune response is often based on labor-intensive techniques that limit the scope of most studies performed. A simple and rapid anthrax toxin-based ELISPOT method to assess HIV-2 cellular immune response was developed. The modified anthrax toxin-based antigen presentation process performed better than a recombinant vaccinia system and the ELISPOT method significantly enhanced the ease and simplicity of the assay. Using this method, a robust HIV-2 cellular immune response directed toward the p26 core protein was exhibited in 21 of 24 (87.5%) infected women, and all 8 seronegative subjects were negative in both assays. Cellular immune responses were associated with low HIV-2 viral load. This simple and rapid modified anthrax toxin-based ELISPOT method allowed us to demonstrate, strong cellular immune responses that may be critical determinants in the HIV-2 attenuated phenotype.

Antigen Presentation↗
PubMed2001

[Anti-hepatitis B virus effects of lamivudine and other five drugs in vitro].

OBJECTIVE: To find out reliable index for evaluating the anti-hepatitis B virus (HBV) effects in vitro of lamivudine (3TC) and other five anti-HBV drugs. METHODS: The contents of human hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg) and hepatitis B virus DNA (HBV DNA) in the culture supernatant of 2.2.15 cell line transfected with hepatitis B virus gene were tested after the six anti-hepatitis B virus drugs were added respectively, and the accordance of different indexes was compared. RESULTS: All six drugs, within a certain range, exercised only weak or no inhibitive effect on extracellular HBsAg and HBeAg secreted by 2.2.15 cell line. Lamivudine and 2 3-dideoxy-3-fluoroguanosine (FLG) significantly inhibited the level of HBV DNA, with the 50% inhibition concentration(IC50) of 0.31 mumol/L and 0.53 mumol/L respectively. Acyclovir (ACV) and interferon-alpha(IFN-alpha) also inhibited the HBV DNA with the IC50 of 0.33 mmol/L and 96.18 U/ml respectively. Phosphonoformate (PFA) and ribavirin (RBV) showed none effect on HBV DNA content even at the maximum non-toxic concentrations. CONCLUSION: There is not accordance between the expression activities of proteins of HBsAg and HBeAg and the inhibition of HBV DNA level. HBV DNA level better reflexes the inhibitive effect of different drugs and can be used as an important index for evaluation of anti-HBV effect in vitro.

Antiviral Agents↗
PubMed2001

Are increased levels of von Willebrand factor in chronic coronary heart disease caused by decrease in von Willebrand factor cleaving protease activity? A study by an immunoassay with antibody against intact bond 842Tyr-843Met of the von Willebrand factor protein.

Low levels of von Willebrand factor (VWF) in von Willebrand's disease type 2A (VWD 2A) result from increased cleavage of the bond 842Tyr-843Met in the VWF protein by VWF cleaving protease. On the other hand, decreased levels of this protease result in unusually large VWF in thrombotic thrombcytopenic purpura with thrombotic complications. In the present study, we designed an enzyme-liked immunosorbent assay of VWF cleaving protease activity to be used to assess whether the high levels of VWF in coronary heart disease (CHD) relate to a deficiency of this protease. Plasma samples with added Pefabloc and CaCl(2) were incubated with purified VWF coated on a microtiter plate. The remaining undigested multimers were quantified by an antibody directed against the intact 842Tyr-843Met bond of the VWF protein. Phosphate-buffered saline (PBS), instead of plasma, was used to obtain the initial level of coated undigested VWF. The reduction in absorbance at 492 nm between PBS and the unknown sample was taken as a measure of the protease activity. The assay was applied to plasma samples from 21 senior women with chronic CHD (cases) and 34 age-matched controls, as well as to samples from three patients with VWD 2A. The protease activity was similar in the two women groups (P>.05), although the VWF antigen levels were higher in the cases (P<.01). The VWD 2A patients had similar plasma levels of the protease to that in normal pooled plasma (NPP). In the senior controls, the protease activity correlated with the subject age (r's=-.61, P<.01, n=34). In conclusion, the developed method is specific for evaluating the protease function on VWF cleavage. The moderate increase of VWF antigen in chronic CHD may not depend on the protease activity. The age influence on the protease levels supports earlier findings of higher VWF levels in healthy older subjects. A high sensitivity of the mutated protein of VWF for the protease effect rather than increases in activity or quantity of the enzyme is probably involved in the pathogenesis of VWD 2A.

ABO Blood-Group System↗
PubMed2001

Photon statistics of random lasers with resonant feedback.

We have measured the photon statistics of random lasers with resonant feedback. With an increase of the pump intensity, the photon number distribution in a single mode changes continuously from Bose-Einstein distribution at the threshold to Poisson distribution well above the threshold. The second-order correlation coefficient drops gradually from 2 to 1. By comparing the photon statistics of a random laser with resonant feedback and that of a random laser with nonresonant feedback, we illustrate very different lasing mechanisms for the two types of random lasers.

Journal Article↗
PubMed2001

Development of a high throughput equilibrium dialysis method.

The identification of large numbers of biologically active chemical entities during high throughput screening (HTS) necessitates the incorporation of new strategies to identify compounds with drug-like properties early during the lead prioritization and development processes. One of the major steps in lead prioritization is an assessment of compound binding to plasma proteins, because it affects both the pharmacokinetics and pharmacodynamics of the compound in vivo. Equilibrium dialysis is the preferred method to determine the free drug fraction, because it is less susceptible to experimental artifacts. However, even low-volume standard equilibrium dialysis is currently not amenable to the HTS format. Those considerations dictate the development of a high throughput equilibrium dialysis device, without compromising the analytical quality of the data. The present paper demonstrates successful development of a 96-well format equilibrium dialysis plate. Plasma protein binding of three drugs, propranolol, paroxetine, and losartan, with low, intermediate, and high binding properties, respectively, were chosen for assay validation. The data indicate that the apparent free fraction obtained by this method correlates with the published values determined by the traditional equilibrium dialysis techniques.

Antidepressive Agents↗
PubMed2001

Single-nucleotide polymorphisms of the proprotein convertase subtilisin/ kexin type 5 (PCSK5) gene.

The proprotein convertase. subtilisin/kexin type 5, or PCSK5, mediates post-translational endoproteolytic processing for several integrin alpha subunits. We identified two silent single-nucleotide polymorphisms (SNPs) in PCSK5, which were found to vary in frequency across ethnic groups. The identification of these amplification primers and SNPs provides tools to investigate PCSK5 for association with inflammatory or vascular phenotypes.

Alleles↗
PubMed2001

Single nucleotide polymorphisms of the resistin (RSTN) gene.

Type 2 diabetes mellitus is a complex phenotype that is frequently associated with central obesity and insulin resistance. Recently, a protein named resistin, encoded by RSTN (OMIM #605565), was identified in adipose tissue. Serum resistin was elevated in obese and diabetic mice, and administration of resistin to normal mice was found to interfere with glucose tolerance and insulin action. Because of these functions, resistin is a candidate gene for diabetes and obesity. Through the use of DNA sequencing, we thus developed amplification primers for rapid screening of the RSTN gene that encodes resistin. No putative mutations were found, but two noncoding single-nucleotide polymorphisms (SNPs) were identified, and these were found to vary in frequency across various ethnic groups. The identification of amplification primers and SNPs provides tools to investigate resistin for association with other phenotypes.

Base Sequence↗