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Biomedical subjects

Q Sun

Publications and source records attributed to Q Sun.

At least 19 recordsLinked to original sources

Stabilization of Si60 cage structure.

A comprehensive search for the stable geometries of bare Si60 and Si60 supported on a C60 fullerene was carried out using first principles calculations based on density functional theory. In contrast to previous theoretical studies and in agreement with recent experiments, we show that Si60 and C(60)@Si(60) clusters are unstable in the fullerenelike cage structure. However, Si60 cage can be stabilized by including within it, as endohedral units, small magic clusters such as Al12X (X=Si, Ge, Sn, Pb) and Ba@Si(20).

Journal Article↗

Two inbred rat strains that differ substantially in hip fragility.

One approach to identifying the genetic influences on skeletal phenotypes involves the creation and genetic mapping of a population of the second filial (F2) offspring derived from a cross of two inbred strains of rodents. The two inbred strains should be chosen based upon a large difference in the phenotype of interest, e.g., bone fragility. We found previously that considerable variation exists in fragility phenotypes among inbred strains of rats, and the phenotypic variation was site specific. In particular, two inbred rat strains, Copenhagen 2331 (COP) and Dark Agouti (DA), were found to differ significantly in femoral neck geometry and strength. The aim of this study was to further characterize hip fragility in COP and DA rats at 6 months of age using peripheral quantitative computed tomography (pQCT), microcomputed tomography (mCT), and biomechanical tests. COP rats had a significantly wider femoral head (P = 0.04) and neck (P = 0.007), significantly larger bone area and cortical bone area in femoral neck (P = 0.03 and P = 0.02, respectively), significantly greater total bone mineral content (BMC) and cortical BMC in femoral neck (P = 0.01 and P = 0.001, respectively), and 65% greater femoral neck cross-sectional moment of inertia (P = 0.02), as compared with DA rats. As a result, COP rats had 22% higher ultimate force (Fu), 68% higher ultimate displacement (du), and 81% higher work to failure (U) than DA rats in the femoral neck biomechanical test (P = 0.04, P = 0.01, and P = 0.02, respectively). The biomechanical properties for the femoral midshaft and lumbar vertebrae were virtually the same in the two rat strains, suggesting a hip-specific genetic effect on bone strength. These data indicate that significant phenotypic variation at the femoral neck site exists between these two inbred strains, and COP rats appear to have genes that specifically enhance the femoral neck structural properties and strength. Therefore these two inbred strains, COP with DA, may facilitate effective genetic studies of hip fragility.

Animals↗

Downregulation of mafB expression in T-helper cells during early differentiation in vitro.

We have studied the expression of a human homologue of mafB (maf-1), a member of the family of large maf transcription factors. In support of the suggested key role that mafB expression plays in differentiating macrophages, we found mafB to be expressed at a very high level in monocytic U937 and THP-1 cell lines. However, we show here that mafB transcription is not restricted to myeloid cells but can also be detected in lymphoid cells, indicating transcriptional plasticity during haematopoiesis. In conclusion, strong proliferative signals mediated by T-cell activation and interleukins (IL-4 and IL-12) downregulate the mafB messenger RNA transcript level when resting naïve CD4+ T-helper cells enter the differentiation pathway in vitro.

Avian Proteins↗

Firing patterns of pre-Bötzinger and Bötzinger neurons during hypocapnia in the adult rat.

Controversy exists about how a coordinated respiratory rhythm is generated in the brainstem. Some authors suggest that neurons in the pre-Bötzinger complex are key to initiation of all types of breathing. While, on the other hand, it has been reported that some pre-Bötzinger neurons fail to maintain a rhythmic discharge in phase with phrenic nerve discharge during mechanical hyperventilation. Extracellular recordings were made from respiratory units in the pre-Bötzinger and Bötzinger complexes of 13 anaesthetised, paralysed and vagotomised rats. Central respiratory activity was monitored from the C5 phrenic nerve. During mechanical hyperventilation, several changes were observed in the phrenic neurogram. Firstly, the frequency and amplitude of integrated phrenic nerve discharge were reduced and reversibly stopped. Secondly, the patterned discharges changed from an augmenting to a variety of non-augmenting patterns in 53 of 60 cases. In some cases (n=9) we observed that the pattern appeared to have two components, an early short duration discharge followed by a longer duration discharge. Respiratory units also started to show different firing patterns during mechanical hyperventilation. In general, they were divided into those units that fired tonically (n=28) and units that became silent (n=32), before phrenic nerve discharge ceased coincidently with complete apnoea. Of particular interest were those expiratory-inspiratory units in the pre-Bötzinger complex (n=8) that narrowed their firing period towards late expiration and early inspiration during mechanical hyperventilation. Given their firing features, it is possible that these expiratory-inspiratory units may participate in generation of the early inspiratory component of phrenic nerve discharge.

Age Factors↗

N-methyl-D-aspartate-induced excitotoxicity in adult rat retina is antagonized by single systemic injection of MK-801.

Intravitreal injection of N-methyl-D-aspartate (NMDA) produced a substantial damage to the adult rat retina that was largely restricted to inner retinal layers, including the ganglion cell layer (GCL), inner nuclear layer (INL), inner, and outer plexiform layers. This retinal damage was significantly reduced by a systemic injection of a low dose of MK-801 (0.5 mg/kg), a potent NMDA-receptor antagonist. This neuroprotection was dose dependent and was most effective when the antagonist was given 1 h before NMDA insult. An intraperitoneal injection of 0.5 mg/kg MK-801 provided a virtually complete protection to the retina to the NMDA-induced toxicity, as indicated quantitatively by the number of DiI-filled retinal ganglion cells, the number of cells in the GCL and INL that undergo DNA fragmentation, and the edematous changes in retinal thickness. A post-lesion administration of MK-801 was still able to provide an effective neuroprotective effect to the retina, but this protection was lost when MK-801 was given 4 h after NMDA exposure. The current results indicate a therapeutic potential of systemic application of MK-801 in protecting the adult rat retina from neurologic disorders related to excessive activation of NMDA receptors.

Animals↗

Estrogen protects against the synergistic toxicity by HIV proteins, methamphetamine and cocaine.

BACKGROUND: Human immunodeficiency virus (HIV) infection continues to increase at alarming rates in drug abusers, especially in women. Drugs of abuse can cause long-lasting damage to the brain and HIV infection frequently leads to a dementing illness. To determine how these drugs interact with HIV to cause CNS damage, we used an in vitro human neuronal culture characterized for the presence of dopaminergic receptors, transporters and estrogen receptors. We determined the combined effects of dopaminergic drugs, methamphetamine, or cocaine with neurotoxic HIV proteins, gp120 and Tat. RESULTS: Acute exposure to these substances resulted in synergistic neurotoxic responses as measured by changes in mitochondrial membrane potential and neuronal cell death. Neurotoxicity occurred in a sub-population of neurons. Importantly, the presence of 17beta-estradiol prevented these synergistic neurotoxicities and the neuroprotective effects were partly mediated by estrogen receptors. CONCLUSION: Our observations suggest that methamphetamine and cocaine may affect the course of HIV dementia, and additionally suggest that estrogens modify the HIV-drug interactions.

Cells, Cultured↗

Effect of six compounds isolated from rhizome of Anemone raddeana on the superoxide generation in human neutrophil.

The effect of six compounds isolated from rhizome of Anemone raddeana on the superoxide generation in human neutrophils was investigated. The six compounds examined were 3-acetyloleanolic acid (AOA), oleanolic acid (OA), eleutheroside K (EK), oleanolic acid-3-O-alpha-L-rhamnopyranosyl-(1 --> 2)-[beta-D-glucopyranosyl-(1 --> 4)]-alpha-L-arabinopyranoside (Rd10), raddeanoside 12 (Rd12) and raddeanoside 13 (Rd13). AOA, OA, Rd12 and Rd13 suppressed the superoxide generation induced by N-formyl-methionyl-leucyl-phenylalanine (fMLP) in a concentration-dependent manner. EK and Rd10 significantly enhanced the fMLP-induced superoxide generation in a specific narrow range of low concentration (0.5-0.75 microM), while these compounds more efficiently suppressed the superoxide generation than the other four compounds in other concentrations. In the case of superoxide generation induced by phorbol 12-myristate 13-acetate (PMA), Rd12, OA, EK and Rd10 dose-dependently suppressed the superoxide generation but AOA and Rd13 gave no effect. Arachidonic acid-induced superoxide generation was suppressed by EK, Rd10, Rd12 and Rd13, but was weakly enhanced by AOA and OA. Rd12 dose-dependently inhibited fMLP-induced tyrosyl phosphorylation of 123.0, 79.4, 60.3, 56.2 and 50.1 kDa proteins in human neutrophil. On the other hand, RD10 and EK enhanced the tyrosyl phosphorylation of these proteins in a low concentration range. These phenomena were parallel to the suppression of the fMLP-induced superoxide generations.

Drugs, Chinese Herbal↗

[Flow cytometry in datecting lymph node micrometastasis in colorectal cancer].

OBJECTIVE: To study the methodology and significance of flow cytometry in detecting lymph node micrometastasis of colorectal cancer. METHODS: One hundred sixty-two cellular suspensions were prepared with lymph nodes which were resected radically on 25 patients with colorectal cancer and in which no cancer cells were found by HE staining. Different concentrations of cultured Lovo colorectal cancer cells were added into the celular suspension prepared from lymph node tissue of persons without colorectal cancer in order to prepare a control model. Dual staining with CK/FTTC and PI was made to the sedimetns from those 2 kinds of suspension. Flow cytometry was used to detect cancer cells. RESULTS: An ideal correlation was obtained between the detection value and the theoretical value of cancer cells in the specimen suspensions and control models (r = 0.097 6) with a sensitivity rate of 10/10(5). Cancer cells were detected from 7 out of the 25 patients and 30 of the 162 cellular suspensions. The detection rate was correlated with the size and infiltrating depth of the cancer. CONCLUSION: Flow cytometry is a reliable, rapid, and quantitative method for detecting lymph node micrometastasis in colorectal cancer.

Colorectal Neoplasms↗

Complex genetic interactions among four receptor tyrosine phosphatases regulate axon guidance in Drosophila.

Four receptor-linked protein tyrosine phosphatases are selectively expressed on central nervous system axons in the Drosophila embryo. Published data show that three of these (DLAR, DPTP69D, DPTP99A) regulate motor axon guidance decisions during embryonic development. Here we examine the role of the fourth neural phosphatase, DPTP10D, by analyzing double-, triple-, and quadruple-mutant embryos lacking all possible combinations of the phosphatases. This analysis shows that all four phosphatases participate in guidance of interneuronal axons within the longitudinal tracts of the central nervous system. In the neuromuscular system, DPTP10D works together with the other three phosphatases to facilitate outgrowth and bifurcation of the SNa nerve, but acts in opposition to the others in regulating extension of ISN motor axons past intermediate targets. Our results provide evidence for three kinds of genetic interactions among the neural tyrosine phosphatases: partial redundancy, competition, and collaboration.

Animals↗

Relationship between thermal parameters and tumor response in hyperthermia combined with radiation therapy.

BACKGROUND: In hyperthermia for cancer therapy, thermal parameters related to tumor response have not yet been clarified. We investigated thermal parameters that could predict tumor response to hyperthermia combined with radiotherapy in locally advanced malignancies. METHODS: Fifty-four patients with locally advanced malignancies who were treated by hyperthermia in combination with radiation therapy were enrolled in this study. Local hyperthermia was induced by ultrasound heating equipment for 60 min, within 30 min after irradiation, twice a week, for a total of six to ten sessions. Radiation therapy was administered with a conventional fractionation regimen, at a total dose of 40-70 Gy. Multi-point thermometry results were obtained with every 10-s temperature data acquisition. An average of seven interstitial sites per tumor was monitored for each treatment. Univariate logistic regression analysis was used to investigate the relationship between tumor response and minimum, maximum, and average intratumor temperature (Tmin, Tmax, Tav); the cumulative minutes of treatment at temperatures exceeded by 90%, 50%, and 10% of the measured intratumoral temperatures (T90, T50, T10); and cumulative minutes of the temperature that achieved above the index temperature value in the tumor center ((Cum min T(center) > T(index)). RESULTS: Complete and partial response rates were 32.6% and 46.2%, respectively. Univariate logistic regression analysis revealed that the temperature parameters with predictive probability were highest for Cum min T(center) > 42.5 degrees C, followed by > 42 degrees C and > 41 degrees C; and T90. Cum min T(center) > 42.5 degrees C was most significantly associated with complete tumor response (P < 0.001). CONCLUSION: These results strongly suggest that hyperthermia is a useful adjunct to radiotherapy for increasing the local control of advanced malignancies, and that Cum min T(center) > 42.5 degrees C could be an important thermal parameter for predicting tumor response.

Adult↗

FtsZ rings in mukB mutants with or without the Min system.

The site of cell division in Escherichia coli is defined by formation of the Z ring between the two segregated daughter nucleoids. Positioning of the Z ring, composed of the highly conserved and tubulin-like FtsZ protein, appears to be negatively regulated by both the nucleoid and the oscillating MinCD inhibitor proteins. MukB protein is probably involved in nucleoid condensation, and in the absence of MukB, the negative effect of the nucleoid on Z rings appears to be partially suppressed. In this study, we examined the localization of Z rings in cells lacking both the Min system and MukB. In the Deltamin DeltamukB double null mutant, essentially all nucleoid-free zones, either at the cell poles or at non-polar sites between nucleoids, contained Z rings. However, a significant proportion of Z rings also formed on top of nucleoids. Interestingly, Z ring clusters often formed at gaps between nucleoids, and some of the rings within the clusters were clearly positioned on top of nucleoids. These results provide further evidence that the negative topological effect of nucleoids in cells lacking MukB is partially but not totally suppressed, and that the absence of the Min system allows more promiscuous Z ring formation.

Adenosine Triphosphatases↗

Synergistic neurotoxicity of opioids and human immunodeficiency virus-1 Tat protein in striatal neurons in vitro.

Human immunodeficiency virus (HIV) infection selectively targets the striatum, a region rich in opioid receptor-expressing neural cells, resulting in gliosis and neuronal losses. Opioids can be neuroprotective or can promote neurodegeneration. To determine whether opioids modify the response of neurons to human immunodeficiency virus type 1 (HIV-1) Tat protein-induced neurotoxicity, neural cell cultures from mouse striatum were initially characterized for mu and/or kappa opioid receptor immunoreactivity. These cultures were continuously treated with morphine, the opioid antagonist naloxone, and/or HIV-1 Tat (1-72) protein, a non-neurotoxic HIV-1 Tat deletion mutant (TatDelta31-61) protein, or immunoneutralized HIV-1 Tat (1-72) protein. Neuronal and astrocyte viability was examined by ethidium monoazide exclusion, and by apoptotic changes in nuclear heterochromatin using Hoechst 33342. Morphine (10nM, 100nM or 1microM) significantly increased Tat-induced (100 or 200nM) neuronal losses by about two-fold at 24h following exposure. The synergistic effects of morphine and Tat were prevented by naloxone (3microM), indicating the involvement of opioid receptors. Furthermore, morphine was not toxic when combined with mutant Tat or immunoneutralized Tat. Neuronal losses were accompanied by chromatin condensation and pyknosis. Astrocyte viability was unaffected. These findings demonstrate that acute opioid exposure can exacerbate the neurodegenerative effect of HIV-1 Tat protein in striatal neurons, and infer a means by which opioids may hasten the progression of HIV-associated dementia.

Animals↗

Development of porcine embryos and offspring after intracytoplasmic sperm injection with liposome transfected or non-transfected sperm into in vitro matured oocytes.

The objective of this study was to evaluate in vitro and in vivo development of porcine in vitro matured (IVM) porcine oocytes fertilised by intracytoplasmic sperm injection (ICSI) and the possibility of producing transgenic embryos and offspring with this procedure. Activated ICSI oocytes had a higher pronuclear formation than non-activated ICSI oocytes (mean 64.8+/-17.3% vs 28.5+/-3.4%, p<0.05). When the zygotes with two pronuclei were cultured to day 2, there was no difference (p<0.05) in the cleavage rate (mean 60.0+/-7.0% vs 63.3+/-12.7%) between the two groups. The blastocyst rate in the activation group was significantly higher than that in the non-activation group (mean 30.0+/-11.6% vs 4.6+/-4.2%, p<0.05). After injection of the sperm transfected with DNA/liposome complex, destabilised enhanced green fluorescent protein (d2EGFP) expression was not observed on day 2 in either cleaved or uncleaved embryos. But from day 3, some of the embryos at the 2-cell to 4-cell stage started to express d2EGFP. On day 7, about 30% of cleaved embryos, which were in the range of 2-cell to blastocyst stage, expressed d2EGFP. However, for the IVF oocytes inseminated with sperm transfected with DNA/liposome complex, and for oocytes injected with sperm transfected with DNA/liposome complex, and for oocytes injected with DNA/liposome complex following insemination with sperm not treated with DNA/liposome complex, none of the embryos expressed d2EGFP. Sixteen day 4 ICSI embryos derived from sperm not treated with DNA/liposome complex were transferred into a day 3 recipient. One recipient delivered a female piglet with normal birthweight. After transfer of the ICSI embryos derived from sperm transfected with DNA/liposome complex, none of the four recipients maintained pregnancy.

Animals↗

Recombination between paralogues at the Rp1 rust resistance locus in maize.

Rp1 is a complex rust resistance locus of maize. The HRp1-D haplotype is composed of Rp1-D and eight paralogues, seven of which also code for predicted nucleotide binding site-leucine rich repeat (NBS-LRR) proteins similar to the Rp1-D gene. The paralogues are polymorphic (DNA identities 91-97%), especially in the C-terminal LRR domain. The remaining family member encodes a truncated protein that has no LRR domain. Seven of the nine family members, including the truncated gene, are transcribed. Sequence comparisons between paralogues provide evidence for past recombination events between paralogues and diversifying selection, particularly in the C-terminal half of the LRR domain. Variants selected for complete or partial loss of Rp1-D resistance can be explained by unequal crossing over that occurred mostly within coding regions. The Rp1-D gene is altered or lost in all variants, the recombination breakpoints occur throughout the genes, and most recombinant events (9/14 examined) involved the same untranscribed paralogue with the Rp1-D gene. One recombinant with a complete LRR from Rp1-D, but the amino-terminal portion from another homologue, conferred the Rp1-D specificity but with a reduced level of resistance.

Amino Acid Sequence↗

Influence of the nucleoid on placement of FtsZ and MinE rings in Escherichia coli.

We previously presented evidence that replicating but unsegregated nucleoids, along with the Min system, act as topological inhibitors to restrict assembly of the FtsZ ring (Z ring) to discrete sites in the cell. To test if nonreplicating nucleoids have similar exclusion effects, we examined Z rings in dnaA (temperature sensitive) mutants. Z rings were excluded from centrally localized nucleoids and were often observed at nucleoid edges. Cells with nonreplicating nucleoids formed filaments, some of which contained large nucleoid-free areas in which Z rings were positioned at regular intervals. Because MinE may protect FtsZ from the action of the MinC inhibitor in these nucleoid-free zones, we examined the localization of a MinE-green fluorescent protein (GFP) fusion with respect to Z rings and nucleoids. Like Z rings, MinE-GFP appeared to localize independently of nucleoid position, forming rings at regular intervals in nucleoid-free regions. Unlike FtsZ, however, MinE-GFP often localized on top of nucleoids, replicating or not, suggesting that MinE is relatively insensitive to the nucleoid inhibition effect. These data suggest that both replicating and nonreplicating nucleoids are capable of topologically excluding Z rings but not MinE.

Bacterial Proteins↗

Resistance gene complexes: evolution and utilization.

More than 30 genes have been characterized from different plant species that provide resistance to a variety of different pathogen and pest species. The structures of most are consistent with a role in pathogen recognition and defense response signaling. Resistance genes are very abundant in plant genomes and most belong to tightly linked gene families. Evolution of R genes is driven by selection on allelic variation created by mutation and re-assorted by recombination between alleles and sometimes between different gene family members. Selection favors genes that can recognize pathogen avr gene products that are present in pathogen populations. Selection at linked gene families favors haplotypes with useful combinations of genes but a limited physiological cost to the plant. Future utilization of R genes will include transfer between related genera and identification or construction of genes that condition durable resistance to variable pathogens. Genes with durable resistance may interact with conserved pathogen elicitors or condition resistance responses that are independent of specific Avr gene interactions.

Evolution, Molecular↗

Normovolemic hemodilution improves oxygen extraction capabilities in endotoxic shock.

We studied the effects of normovolemic hemodilution on tissue oxygen extraction capabilities in a canine model of endotoxic shock. Eighteen anesthetized and mechanically ventilated dogs underwent normovolemic hemodilution with 6% hydroxyethyl starch solution to reach hematocrit (Hct) levels around 40, 30, or 20% before the administration of 2 mg/kg of Escherichia coli endotoxin. Cardiac tamponade was then induced by repeated injections of normal saline into the pericardial sac to reduce cardiac output and study whole body oxygen extraction capabilities. Whole body critical oxygen delivery was lower in the Hct 20% and 30% groups (8.4 +/- 0.4 and 10.4 +/- 0.7 ml. kg(-1). min(-1), respectively) than in the Hct 40% group (12.8 +/- 0.8 ml. kg(-1). min(-1)) (both P < 0.005). The whole body critical oxygen extraction ratio was higher in the Hct 30% and 20% groups (49.1 +/- 8.2 and 55.2 +/- 4.6%, respectively) than in the Hct 40% group (37.1 +/- 4.4 %) (both P < 0.05). Liver critical oxygen extraction ratio was also higher in the Hct 30% and 20% groups than in the Hct 40% group. The arterial lactate concentrations and the gradient between ileum mucosal PCO(2) and arterial PCO(2) were lower in the Hct 20% and 30% groups than in the Hct 40% group. We conclude that, during an acute reduction in blood flow during endotoxic shock in dogs, normovolemic hemodilution is associated with improved tissue perfusion and increased oxygen extraction capabilities.

Animals↗