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Biomedical subjects

Kai Wang

Publications and source records attributed to Kai Wang.

At least 55 records · Page 3Linked to original sources

Serum albumin, C-reactive protein, interleukin 6, and fetuin a as predictors of malnutrition, cardiovascular disease, and mortality in patients with ESRD.

BACKGROUND: Serum albumin (S-Alb), C-reactive protein (CRP), and interleukin 6 (IL-6) predict malnutrition, atherosclerotic cardiovascular disease (CVD), and mortality in patients with end-stage renal disease (ESRD). Fetuin A, an inhibitor of vascular calcification, also is associated strongly with clinical outcome in patients with ESRD. In this study, multivariate analyses were performed to assess these 4 biomarkers as predictors of malnutrition, CVD, and mortality in patients with ESRD. METHODS: One hundred seventy-six patients with ESRD (54 +/- 12 years) underwent measurements of S-Alb, high-sensitivity CRP (hs-CRP), plasma IL-6, and fetuin A close to the start of dialysis therapy and were followed up for a median of 26 months (range, 1 to 66 months). Nutritional status was evaluated by means of subjective global assessment. CVD was defined based on medical history. Associations between biomarker levels and malnutrition, CVD, and mortality were evaluated by means of receiver operating characteristic curve, logistic regression analysis, and Cox proportional hazards model. RESULTS: All 4 biomarkers predicted malnutrition, CVD, and mortality. Multivariate analysis, according to receiver operating characteristic analysis, showed that malnutrition was predicted best by hs-CRP and IL-6 levels; CVD, by IL-6 level; and mortality, by albumin and IL-6 levels. When using the cutoff levels derived from receiver operating characteristics, logistic regression analysis showed that only hs-CRP level (odds ratio [OR], 3.6) was associated with malnutrition, and only IL-6 level (OR, 3.7) was associated with CVD. Levels of S-Alb, IL-6, and fetuin A, but not hs-CRP, were associated with increased relative risk for mortality as assessed by Cox in a model adjusting for age, sex, and diabetes mellitus. CONCLUSION: Multivariate analyses show that in patients with ESRD, malnutrition is predicted best by hs-CRP and IL-6 levels; CVD, by IL-6 level; and mortality, by S-Alb, IL-6, and fetuin A levels, but not by hs-CRP level. This comparative analysis indicates that of these biomarkers, IL-6 level may be the most reliable predictor of CVD and mortality in patients with ESRD.

Adult↗

[Application of complete audiological evaluation battery in early hearing aid fitting for deaf children].

OBJECTIVE: To investigate the function of ABR and behavioral test battery in verifying the fitting of hearing aids on deaf children at early stage. METHOD: Fifty-two children of age 1 to 9 were examined with the behavioral test battery or ABR. Based on the hearing thresholds thus obtained, DSL prescriptive formula was used to verify the fitting of hearing aids. Real ear measurement and sound field test were employed to assess the benefit of hearing aid. The children were subsequently followed up on a regular basis. RESULT: There was statistic difference between ABR and behavioral test battery (P < 0.05). Forty-one deaf children demonstrated significant benefit from hearing aid fitting while 4 showed no measurable benefit. CONCLUSION: Both subjective and objective tests should be used for accurate hearing evaluation in deaf children. Hearing aid verification should be conducted accordingly. It is important to carry out early identification, intervention and rehabilitation.

Audiometry↗

[Construction of rAAV2-GPIIb/IIIa vector and test of its expression and function in vitro].

This study was aimed to explore the possibility of rAAV2 vector-mediating gene therapy for Glanzmann' s thrombasthenia. The rAAV2-GPIIb/IIIa vector was constructed. The GPIIb/IIIa gene expression in mammal cell were examined by different methods, such as: detection of mRNA expression in BHK-21 cells after 24 hours of infection (MOI = 1 x 10(5) v.g/cell) was performed by RT-PCR; the relation between MOI and quantity of GPII6/IIIa gene expression was detected by FACS after 48 hours of infection; GPIIb/IIIa protein expression in BHK-21 cells after 48 hours of infection (MOI = 10(5) v x g/cell) was assayed by Western blot, GPIIb/IIIa protein expression on cell surface was detected by immunofluorescence, and the biological function of expressing product was determined by PAC-1 conjunct experiments. The results showed that GPIIb/IIIa gene expression in mRNA level could be detected in BHK-21 cells after 24 hours of infection at MOI = 1 x 10(5) v x g/cell and the GPIIb/IIIa gene expression in protein level could be detected in BHK-21 cells after 48 hours of infection at MOI = 1 x 10(5) v x g/cell. In certain range, quantity of GPIIb/IIIa gene expression increased with MOI, but overdose of MOI decreased quantity of GPIIb/IIIa gene expression. Activated product of GPIIb/IIIa gene expression could combined with PAC-I, and possesed normal biological function. In conclusion, rAAV2 vactor can effectively mediate GPIIb and GPIIIa gene expressing in mammal cells, and the products of these genes exhibit biological function. This result may provide a basis for application of rAAV2 vector in Glanzmann's thrombasthenia gene therapy in furture.

Dependovirus↗

[Effects of different donor cells and passages on the development of nuclear transfer porcine embryos].

This study was undertaken to systematically examine effects of different donor cells and passages on the development of nuclear transfer porcine embryos, so as to establish a preliminary procedure for porcine cloning. Porcine oocytes obtained from ovaries at slaughter were matured in vitro for 40-44h and then enucleated in manipulation medium containing 5 microg/mL cytochalasin B. Fibroblast cells (FC), oviduct epithelial cells (OEC), granulosa cells (GC) and cumulus cells(CC) after 3-9 passages in TCM + 10% FBS were treated by serum starvation (0.5% FBS for 2-9 days), 0.1 microg/mL aphidiconlin (APD) for 1 day and 0.5% FBS for 2-9 days or continue culturing in 10% FBS for 2-9 days, then, were transferred into enucleated oocytes by microinjection or electronic fusion (100 V/mm, 30 micros and 1 pulses). Reconstituted embryos were activated with a combination of calcium ionophore A23187 or electric pulse and 6-DMAP, and cultured for 6 days, to evaluate their cleavage and embryonic development. The cleavage rate of embryos reconstructed with FC and GC pretreated with 0.1 microg/mL APD + 0.5% FBS were significantly higher than that of serum starvation group and control group (P<0.01). There was significantly difference in the cleavage rate and embryonic development among embryos derived from GC, CC and FC, OEC pretreated with 0.1 microg/mL APD + 0.5% FBS. The cleavage rate of embryos reconstructed with GC by electrofusion was significantly higher than that by microinjection (P<0.05), but no difference was found in their proportion developing to blastocysts. 75% to 85% of GC at 3 and 6 passages, and FC at 6 and 10 passages had normal karyotype, which did not show significant difference among them (P>0.05). When GC at G3, G4, G5 and G6 of passages were used as donor cells, the cleavage rate and blastocyst rate was similar, moreover, FC at G6, G7, G8 and G9 of passages also resulted in a similar cleavage rate and blastocyst development. These results indicate that: (1) FC and GC can be cultured up to 9 passages and keep relatively stable karyotepe; (2) Using 0.1 microg/mL APD to treat donor cells prior to nuclear transfer can improve the efficiency of somatic cell nuclear transfer in buffalo but serum starvation is inefficient in our system; (3) Both of FC and GC cells can be used as the donor karyoplasts for nuclear transfer, and their efficiency are not influenced by the culture passages; (4) The development of reconstructed embryos by electrofusion is higher than that by microinjection, but there is no difference in the total efficiency between the two methods.

Adenine↗

Peroxisome proliferator-activated receptor gamma down-regulates receptor for advanced glycation end products and inhibits smooth muscle cell proliferation in a diabetic and nondiabetic rat carotid artery injury model.

Diabetes is associated with an increase in circulating advanced glycosylation end products (AGEs) and the increased expression of the receptor for AGEs (RAGE). Inhibition of AGE/RAGE binding through the administration of soluble RAGE (sRAGE) has been shown to decrease neointimal hyperplasia. Peroxisome proliferator-activated receptor gamma (PPARgamma), which inhibits neointimal hyperplasia, has been shown to decrease RAGE expression in cultured endothelial cells. We hypothesized that PPARgamma agonists inhibit neointimal hyperplasia via down-regulation of RAGE in vivo. Pretreatment of rat aortic smooth muscle cells (SMCs) with PPARgamma agonist rosiglitazone significantly down-regulated RAGE expression and inhibited SMC proliferation in response to the RAGE agonist S100/calgranulins. In vivo studies showed that rosiglitazone decreased RAGE expression and SMC proliferation at 7 days following carotid arterial injury in both diabetic and nondiabetic rats. At 21 days following injury, neointimal formation was significantly decreased in both diabetic and nondiabetic animals that received rosiglitazone. To determine whether inhibition of neointimal formation by PPARgamma activation could fully be accounted for by its down-regulation of RAGE, we compared the results obtained in animals treated with sRAGE, PPARgamma activator, and sRAGE + PPARgamma activator. Consistent with PPARgamma working through its effects on RAGE, we found that the addition of PPARgamma activator to sRAGE did not result in any further decrease in neointimal formation. These data demonstrate for the first time that PPARgamma agonists inhibit RAGE expression at sites of arterial injury and suggest that down-regulation of RAGE by the PPARgamma activation inhibits neointimal formation in response to arterial injury.

Animals↗

Event-related potentials in adolescents with combined ADHD and CD disorder: a single stimulus paradigm.

Some studies of the event-related potentials demonstrated a reduction of the voluntary component P3 (P300 or P3b) in youngsters with the attention deficit/hyperactivity disorder (ADHD) or in conduct disorders (CD), and a reduction of the automatic processing component, mismatch negativity, in patients with both ADHD and CD (ADHD+CD). Recently, a passive auditory P3 potential has been elicited by a single stimulus. We therefore tried this potential study in 20 healthy subjects and 20 teenagers with ADHD+CD to search for further evidence of the altered automatic cerebral processing in the latter. Subjects also answered a self-report Dimensional Assessment of Personality Pathology (DAPP). The patient group scored significantly higher on most DAPP traits that reflect problems of emotion control, showed significantly prolonged P2, N2, and P3, and reduced P3. In all subjects Stimulus Seeking was positively correlated with P3 latencies at Fz, Cz, and Pz, and with P3 amplitude at Cz. This study suggests that youngsters with ADHD+CD had pronounced emotion dysregulation, and prominent deficit in passive attention, as reflected by the automatic processing of auditory stimuli.

Adolescent↗

Binding and photocleavage of cationic porphyrin-phenylpiperazine hybrids to DNA.

The binding properties of cationic porphyrin-phenylpiperazine hybrids to calf thymus (CT) DNA were investigated by using absorption, fluorescence and circular dichroism (CD) spectra, and the apparent affinity binding constants (K(app)) of the porphyrins for CT DNA were determined by using a competition method with ethidium bromide (EB). Intercalation of porphyrin into CT DNA occurred when two phenylpiperazines were introduced at cis position onto the periphery of cationic porphyrin. The photocleavages of pBR322 plasmid DNA by the porphyrins were consistent with the values of K(app). With [porphyrin]/[DNA base pairs] ratio increased, the binding mode tended to be outside binding, and the cleavage abilities of the porphyrins varied. In the presence of sodium azide, a quencher of 1O2, the cleavage of DNA by the porphyrin of intercalation was less inhibited.

Animals↗

Selective impairment of attentional networks of orienting and executive control in schizophrenia.

BACKGROUND: Difficulty attending is a common deficit of schizophrenic patients. However, it is not known whether this is a global attentional deficit or relates to a specific attentional network. METHOD: This study used the attention network test to compare schizophrenic patients (N=77) with controls (N=53) on the efficiency of three anatomically defined attentional networks: alerting, orienting, and executive control. RESULTS: Schizophrenic patients showed a large and highly significant deficit in the executive network and a smaller but significant deficit in the orienting network as well as in overall RT and accuracy. There was no deficit in the alerting network. CONCLUSION: These results suggest some specificity in the attentional networks influenced by the disorder. The executive attention network has been shown in normal subjects to activate the anterior cingulate and lateral prefrontal areas. Previous data using neuroimaging with schizophrenic patients has shown abnormal control by the anterior cingulate. Our findings support this previous research by indicating that the major attentional deficit in schizophrenic patients is in a network that includes the anterior cingulate.

Adult↗

Prose memory deficits associated with schizophrenia.

Memory of contextual information is essential to one's quality of living. This study investigated if the different components of prose memory, across three recall conditions: first learning trial immediate recall, fifth learning trial immediate recall, and 30-min delayed recall, are differentially impaired in people with schizophrenia, relative to healthy controls. A total of 39 patients with schizophrenia and 39 matched healthy controls were recruited. Their prose memory, in terms of recall accuracy, temporal sequence, recognition accuracy and false positives, commission of distortions, and rates of learning, forgetting, and retention were tested and compared. After controlling for the level of intelligence and depression, the patients with schizophrenia were found to commit more distortions. Furthermore, they performed poorer on recall accuracy and temporal sequence accuracy only during the first initial immediate recall. On the other hand, the rates of forgetting/retention and recognition accuracy were comparable between the two groups. These findings suggest that people with schizophrenia could be benefited by repeated exposure to the materials to be remembered. These results may have important implications for rehabilitation of verbal declarative memory deficits in schizophrenia.

Adult↗

Effects of the sequence and size of non-polar residues on self-assembly of amphiphilic peptides.

Peptides with alternating hydrophobic and polar amino acids have been shown to form stable beta-sheet secondary structures and self-assemble into hydrogel-like matrices in the presence of physiological salt concentrations. We hypothesized that the sequence and steric size differences of non-polar residues can affect the balance of peptide intermolecular forces in solution that drive self-assembly. To test this hypothesis, we designed a library of artificial amphiphilic peptides based on the sequence (FEFEFKFK)2 by substituting combinations of the non-polar residues glycine, alanine, valine, leucine and isoleucine for phenylalanine. Peptide structure and self-assembly were characterized using scanning electron microscopy, the Thioflavin T assay, transmission electron microscopy, X-ray fiber diffraction and circular dichroism spectroscopy. The sequence and steric size of non-polar residues are shown to cause variations in peptide secondary structures and create significant differences in the matrix morphology of self-assembled peptides.

Alanine↗

A constrained-likelihood approach to marker-trait association studies.

Marker-trait association analysis is an important statistical tool for detecting DNA variants responsible for genetic traits. In such analyses, an analysis model of the mean genetic effects of the genotypes is often specified. For instance, the effect of the disease allele on the trait is often specified to be dominant, recessive, additive, or multiplicative. Although this model-based approach is powerful when the analysis model is correctly specified, it has been found to have low power sometimes when the specified model is incorrect. We introduce an approach that does not require the specification of a particular genetic model. This approach is built upon a constrained maximum likelihood in which the mean genetic effect of the heterozygous genotype is required to not exceed those of the two homozygous genotypes. The asymptotic distribution of the likelihood-ratio statistic is derived for two special cases. A simulation study suggests that this new approach has power comparable to that of the model-based method when the analysis model is correctly specified. This approach uses one marker at a time (i.e., it is a single-marker analysis). However, given the latest findings that powerful inferential procedures for haplotype analyses can be constructed from single-marker analyses, we expect this approach to be useful for haplotype analyses.

Alleles↗

Excitation-contraction coupling gain and cooperativity of the cardiac ryanodine receptor: a modeling approach.

During calcium-induced calcium-release, the ryanodine receptor (RyR) opens and releases large amounts of calcium from the sarcoplasmic reticulum into the cytoplasm of the myocyte. Recent experiments have suggested that cooperativity between the four monomers comprising the RyR plays an important role in the dynamics of the overall receptor. Furthermore, this cooperativity can be affected by the binding of FK506 binding protein, and hence, modulated by adrenergic stimulation through the phosphorylating action of protein kinase A. This has important implications for heart failure, where it has been hypothesized that RyR hyperphosphorylation, resulting in a loss of cooperativity, can lead to a persistent leak and a reduced sarcoplasmic-reticula content. In this study, we construct a theoretical model that examines the cooperativity via the assumption of an allosteric interaction between the four subunits. We find that the level of cooperativity, regulated by the binding of FK506 binding-protein, can have a dramatic effect on the excitation-contraction coupling gain and that this gain exhibits a clear maximum. These findings are compared to currently available data from different species and allows for an evaluation of the aforementioned heart-failure scenario.

Allosteric Site↗

Electrophysiological properties of pluripotent human and mouse embryonic stem cells.

Pluripotent embryonic stem cells (ESCs) possess promising potential for cell-based therapies, but their electrophysiological properties have not been characterized. Here we describe the presence of ionic currents in mouse (m) and human (h) ESCs and their physiological function. In mESCs, tetraethylammonium (TEA)-sensitive depolarization-activated delayed rectifier K+ currents (IK(DR)) (8.6 +/- 0.9 pA/pF at +40 mV; IC50 = 1.2 +/- 0.3 mM), which contained components sensitive to 4-aminopyridine (4-AP) (IC50 = 0.5 +/- 0.1 mM) and 100 nM Ca2+-activated K+ current (IK(Ca)) blocker iberiotoxin (IBTX),were detected in 52.3% of undifferentiated cells.IK(DR) was similarly present in hESCs (approximately 100%) but with an approximately sixfold higher current density (47.5 +/- 7.9 pA/pF at +40 mV). When assayed by bromodeoxyurindine incorporation, application of TEA, 4-AP, or IBTX significantly reduced the proliferation of mESCs and hESCs in a dose-dependent manner (p < .05). A hyperpolarization-activated inward current (I(h)) (-2.2 +/- 0.4 pA/pF at -120 mV) was detected in 23% of mESCs but not hESCs. Neither Na(v) nor Ca(v) currents were detected in mESCs and hESCs. Microarray and reverse transcription-polymerase chain reaction analyses identified several candidate genes for the ionic currents discovered. Collectively, our results indicate that pluripotent ESCs functionally express several specialized ion channels and further highlight similarities and differences between the two species. Practical considerations for the therapeutic use of ESCs are discussed.

4-Aminopyridine↗

Platelet, not endothelial, P-selectin is required for neointimal formation after vascular injury.

BACKGROUND: P-selectin blockade significantly inhibits inflammation and neointimal formation after arterial injury; however, the independent roles of platelet and endothelial P-selectins in this process are unknown. In atherosclerosis, both platelet and endothelial cell P-selectins are important. This study was designed to determine whether P-selectin expression on platelet, endothelial, or both surfaces is critical to the inflammatory response and neointimal formation after arterial injury. METHODS AND RESULTS: Using wild-type (WT) and P-selectin-knockout (Psel(-/-)) mice, we performed bone marrow transplantation to generate chimeric mice that expressed either platelet P-selectin (Plt-Psel) or endothelial P-selectin (EC-Psel). Double injury of the carotid artery was performed in these mice as well as in WT and Psel(-/-) mice. Animals were euthanized 4 or 21 days after arterial injury. Morphometric data showed that there was more neointimal formation in the WT mouse group when compared with the Psel(-/-) mouse group (0.015+/-0.004 vs 0.004+/-0.004 mm2, P<0.001). Further comparison showed significantly less neointimal area in EC-Psel mice (0.006+/-0.004 mm2) compared with Plt-Psel mice (0.011+/-0.005 mm2, P=0.026) and WT mice (0.015+/-0.004 mm2, P=0.001). No significant differences were observed between WT and Plt-Psel mice or between Psel(-/-) and EC-Psel mice. Decreased neointimal formation was accompanied by a reduced inflammatory response, as evidenced by immunostaining of RANTES and MCP-1 4 days after injury. CONCLUSIONS: Platelet P-selectin expression, but not endothelial P-selectin, plays a crucial role in the development of neointimal formation after arterial injury, and therapeutic strategies targeting leukocyte-platelet interactions could be effective in inhibiting restenosis.

Angioplasty, Balloon↗

Interchromosomal segmental duplications explain the unusual structure of PRSS3, the gene for an inhibitor-resistant trypsinogen.

Homo sapiens possess several trypsinogen or trypsinogen-like genes of which three (PRSS1, PRSS2, and PRSS3) produce functional trypsins in the digestive tract. PRSS1 and PRSS2 are located on chromosome 7q35, while PRSS3 is found on chromosome 9p13. Here, we report a variation of the theme of new gene creation by duplication: the PRSS3 gene was formed by segmental duplications originating from chromosomes 7q35 and 11q24. As a result, PRSS3 transcripts display two variants of exon 1. The PRSS3 transcript whose gene organization most resembles PRSS1 and PRSS2 encodes a functional protein originally named mesotrypsinogen. The other variant is a fusion transcript, called trypsinogen IV. We show that the first exon of trypsinogen IV is derived from the noncoding first exon of LOC120224, a chromosome 11 gene. LOC120224 codes for a widely conserved transmembrane protein of unknown function. Comparative analyses suggest that these interchromosomal duplications occurred after the divergence of Old World monkeys and hominids. PRSS3 transcripts consist of a mixed population of mRNAs, some expressed in the pancreas and encoding an apparently functional trypsinogen and others of unknown function expressed in brain and a variety of other tissues. Analysis of the selection pressures acting on the trypsinogen gene family shows that, while the apparently functional genes are under mild to strong purifying selection overall, a few residues appear under positive selection. These residues could be involved in interactions with inhibitors.

Chromosomes, Human↗

FSSA: a novel method for identifying functional signatures from structural alignments.

MOTIVATION: It is commonly believed that sequence determines structure, which in turn determines function. However, the presence of many proteins with the same structural fold but different functions suggests that global structure and function do not always correlate well. RESULTS: We propose a method for accurate functional annotation, based on identification of functional signatures from structural alignments (FSSA) using the Structural Classification of Proteins (SCOP) database. The FSSA method is superior at function discrimination and classification compared with several methods that directly inherit functional annotation information from homology inference, such as Smith-Waterman, PSI-BLAST, hidden Markov models and structure comparison methods, for a large number of structural fold families. Our results indicate that the contributions of amino acid residue types and positions to structure and function are largely separable for proteins in multi-functional fold families.

Algorithms↗

The antipsychotic and antiemetic drug prochlorperazine delays the ventricular repolarization of the in situ canine heart.

Electropharmacological effect of the antipsychotic and antiemetic drug prochlorperazine was assessed using the halothane-anesthetized in vivo canine model (n = 5). Up to 10 times higher than the clinically relevant doses of prochlorperazine (< or = 3 mg/kg, i.v.) did not induce cardiohemodynamic collapse in the model. Meanwhile, clinically relevant to supratherapeutic doses (0.3 - 3 mg/kg, i.v.) prolonged the ventricular repolarization period in a dose-related and reverse-use dependent manner that could become proarrhythmic substrates. Thus, caution has to be paid on the use of prochlorperazine particularly for patients with risks of the elevated plasma drug concentration, compromised cardiac repolarization, and/or frequent ventricular premature beats.

Action Potentials↗