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Yan Yang

Publications and source records attributed to Yan Yang.

At least 91 records · Page 5Linked to original sources
PubMed2004

Interaction between altered insulin and lipid metabolism in CEACAM1-inactive transgenic mice.

Inactivation of CEACAM1 in L-SACC1 mice by a dominant-negative transgene in liver impairs insulin clearance and increases serum free fatty acid (FFA) levels, resulting in insulin resistance. The contribution of elevated FFAs in the pathogenesis of insulin resistance is herein investigated. Treatment of L-SACC1 female mice with carnitine restored plasma FFA content. Concomitantly, it normalized insulin levels without directly regulating receptor-mediated insulin internalization and prevented glucose tolerance in these mice. Similarly, treatment with nicotinic acid, a lipolysis inhibitor, restored insulin-stimulated receptor uptake in L-SACC1 mice. Taken together, these data suggest that chronic elevation in plasma FFAs levels contributes to the regulation of insulin metabolism and action in L-SACC1 mice.

3-Hydroxybutyric Acid↗
PubMed2004

Complete complement components C4A and C4B deficiencies in human kidney diseases and systemic lupus erythematosus.

Although a heterozygous deficiency of either complement component C4A or C4B is common, and each has a frequency of approximately 20% in a Caucasian population, complete deficiencies of both C4A and C4B proteins are extremely rare. In this paper the clinical courses for seven complete C4 deficiency patients are described in detail, and the molecular defects for complete C4 deficiencies are elucidated. Three patients with homozygous HLA A24 Cw7 B38 DR13 had systemic lupus erythematosus, mesangial glomerulonephritis, and severe skin lesions or membranous nephropathy. Immunofixation, genomic restriction fragment length polymorphisms, and pulsed field gel electrophoresis experiments revealed the presence of monomodular RP-C4-CYP21-TNX (RCCX) modules, each containing a solitary, long C4A mutant gene. Sequencing of the mutant C4A genes revealed a 2-bp, GT deletion in exon 13 that leads to protein truncation. The other four patients with homozygous HLA A30 B18 DR7 had SLE, severe kidney disorders including mesangial or membranoproliferative glomerulonephritis, and/or Henoch Schoenlein purpura. Molecular genetic analyses revealed an unusual RCCX structure with two short C4B mutant genes, each followed by an intact gene for steroid 21-hydroxylase. Nine identical, intronic mutations were found in each mutant C4B. In particular, the 8127 g-->a mutation present at the donor site of intron 28 may cause an RNA splice defect. Analyses of 12 complete C4 deficiency patients revealed two hot spots of deleterious mutations: one is located at exon 13, the others within a 2.6-kb genomic region spanning exons 20-29. Screening of these mutations may facilitate epidemiologic studies of C4 in infectious, autoimmune, and kidney diseases.

Adolescent↗
PubMed2004

Genetic evidence for an interaction between a picornaviral cis-acting RNA replication element and 3CD protein.

Internally located, cis-acting RNA replication elements, termed cres, are essential for replication of the genomes of picornaviruses such as human rhinovirus 14 (HRV-14) and poliovirus because they template uridylylation of the protein primer, VPg, by the polymerase 3D(pol). These cres form stem-loop structures sharing a common loop motif, and the HRV-14 cre can substitute functionally for the poliovirus cre in both uridylylation in vitro and RNA replication in vivo. We show, however, that the poliovirus cre is unable to support HRV-14 RNA replication. This lack of complementation maps to the stem of the poliovirus cre and was reversed by single nucleotide substitutions in the stem as well as the base of the loop. Replication-competent, revertant viruses rescued from dicistronic HRV-14 RNAs containing the poliovirus cre, or a chimeric cre containing the poliovirus stem, contained adaptive amino acid substitutions. These mapped to the surface of both the polymerase 3D(pol), at the tip of the "thumb" domain, and the protease 3C(pro), on the side opposing the active site and near the end of an extended strand segment implicated previously in RNA binding. These mutations substantially enhanced replication competence when introduced into HRV-14 RNAs containing the poliovirus cre, and they were additive in their effects. The data support a model in which 3CD or its derivatives 3C(pro) and 3D(pol) interact directly with the stem of the cre during uridylylation of VPg.

Base Sequence↗
PubMed2004

An efficient therapeutic approach to patients with acute promyelocytic leukemia using a combination of arsenic trioxide with low-dose all-trans retinoic acid.

The use of arsenic trioxide (As2O3, ATO) combined with all-trans retinoic acid (ATRA) has recently been reported to induce remission in patients with acute promyelocytic leukemia (APL). However, its efficiency remains inconclusive mainly due to the small number of the available cases. In this study, therefore, we present a clinical study using a combination of ATO with low-dose ATRA (LD-ATRA) to treat 108 APL patients (80 newly diagnosed patients, 28 relapsed patients). Therapeutic outcomes using the ATO/LD-ATRA approach were compared with those of APL patients treated either with ATO alone (65 patients) or ATRA alone (51 patients). The results showed that the ATO/LD-ATRA approach provided significantly better therapeutic outcomes as compared to either ATO or ATRA alone, as evidenced by lower mortality, a higher CR rate and a reduced period to CR. In addition, the toxic side-effects have been no worse with the combined ATO/LD-ATRA treatment than with either ATO or ATRO alone and in some cases have been reduced. These data suggest that the ATO/LD-ATRA regimen is superior to either regimen given alone to patients with APL.

Adolescent↗
PubMed2004

Genetic approaches to studying mouse models of human seizure disorders.

In conclusion, we have discussed a reverse genetics approach to studying seizure disorders in mice (Fig. 1), employing a targeted mutagenesis method to exploit the genetic defects identified in human epilepsy families. After detailed characterization of the nature of the human mutation and the mouse counterpart gene, a targeting vector containing the human disease allele is created. The endogenous mouse gene is replaced by the human disease allele through homologous recombination in ES cells, leading to the generation of chimeric animals. Mice carrying one copy or both copies of the human mutation can be bred to study the phenotypic effect of heterozygous and homozygous mutations. At this stage, one may want to split the newly created mice into two groups. One group will go through seizure phenotyping tests, while the other group will be used to generate disease allele-carrying mice on a different genetic background. Phenotypic characterization of mice on different inbred strains includes behavioral monitoring and EEG analysis looking for the occurrence of spontaneous seizures, as well as routine cage examination looking for handling-provoked seizure and ECT- and PTZ- induced seizure paradigms looking for sensitivity to these stimuli. A complete evaluation of the seizure phenotype at the whole-animal level establishes the relevance of the mouse model to the human condition. Further investigation including imaging, electrophysiology and AED response in these mouse models will shed light on the mechanistic basis of the convulsive disorder. Current epilepsy research in mouse genetics offers promise for understanding the molecular mechanisms that underlie epileptogenesis in humans. A large-scale forward genetic effort to create novel mouse mutants with seizure phenotypes by in vivo chemical mutagenesis with ethyl-nitroso urea (ENU) is underway at the Jackson Laboratory (http://www.jax.org/nmf/). Genetic mapping and isolation of the affected genes in these seizure-prone models will provide additional molecular pathways involved in seizures. The mutant mice generated through both forward and reverse genetic approaches will be a valuable resource for the biomedical community to study epilepsy at the molecular level and to characterize the pathological consequences of seizures in the whole organism.

Animals↗
PubMed2004

Evaluation of unscanned-mode soft-tissue thermal index for rectangular sources and proposed new indices.

The monopole-source solution was used to calculate the three-dimensional complex acoustic pressure field for one-dimensional focused rectangular apertures in a medium having homogeneous acoustic and thermal properties. For each of six frequencies (1, 3, 5, 7, 9 and 12 MHz) and three focuses (f/1, f/2 and f/4), 33 rectangular aperture cases were investigated, for a total of 594 cases. For these focused field geometries, the three-dimensional temperature distribution was calculated using the bioheat transfer equation in homogeneous perfused media (attenuation = absorption: 0.3 dB/cm-MHz; perfusion length: 1.0 cm). For each of the 594 cases, the acoustic field was normalized to the derated spatial-peak temporal-average intensity (ISPTA.3) of 720 mW/cm2, the maximum value condition allowed based on the U.S. Food and Drug Administration (FDA) regulatory limit for most diagnostic ultrasound (US) equipment. Using the normalized acoustic field, the axial temperature increase profiles and the maximum temperature increases (DeltaTmax) were determined for each case. Also, from the normalized acoustic field, the unscanned-mode soft-tissue thermal index (TIS) for the rectangular sources was determined according to the procedures of the Standard for Real-Time Display of Thermal and Mechanical Indices on Diagnostic Ultrasound Equipment, commonly called the output display standard, ODS. The DeltaTmax:TIS ratio of the 594 cases yielded a mean value of 0.22, a median value of 0.16, a maximum value of 1.04 and a minimum value of 0.039. For all but one of the cases, TIS was greater than DeltaTmax. Also, two new unscanned-mode soft-tissue thermal indices (denoted TIS(new1) and TIS(new2)) were proposed. For new model 1, the DeltaTmax: TIS(new1) ratio yielded a mean value of 1.02, a median value of 1.01, a maximum value of 1.83 and a minimum value of 0.44. For new model 2, the DeltaTmax: TIS(new2) ratio yielded a mean value of 1.04, a median value of 0.99, a maximum value of 2.31 and a minimum value of 0.34. Further, both new models fit more closely to DeltaTmax than does the ODS-determined TIS and have the potential of being easier for manufacturers to implement because only the source power and frequency need to be measured.

Connective Tissue↗
PubMed2004

Excess risk thresholds in ultrasound safety studies: statistical methods for data on occurrence and size of lesions.

Concerns about the safe use of clinical ultrasound (US) at diagnostic pressure levels (below a mechanical index, or MI, = 1.9) have stimulated considerable research in US risk assessment. The objective of the present study was to develop probability-based risk thresholds for US safety studies, to present statistical methods for estimating the thresholds and their standard errors and to compare these methods with the analysis based on a piecewise linear ("hockey stick") model. The excess risk at exposure level x > 0 was defined as the relative increase in the probability of a lesion at that level compared with the background probability of a lesion at exposure x = 0. The risk threshold was then defined as the exposure level at which the excess risk exceeded a specified level (e.g. 5% or 50%). Thus, given pressure-dependent estimates of the excess risk, the thresholds were estimated by solving the risk equation to obtain the pressure at which the target level of excess risk occurs. Threshold estimates of this type have been developed extensively in the literature for incidence (presence or absence) data. Only recently, however, have excess risk threshold estimates been derived for data in which lesion size (depth, surface area) is measured if present and a zero is recorded if the lesion is absent. Tobit regression was used to estimate pressure-dependent percentiles of the size distribution, and the excess risks were estimated from the tobit probability of a positive-valued response. The tobit model provides a well-established approach to modeling data constrained to be nonnegative. Solving the risk equation for the tobit model leads to risk threshold estimates that incorporate the information on size of observed lesions. Results using these probability-based risk estimates were compared with results for a piecewise linear ("hockey stick") model, which has also been used in the US safety literature, although it does not explicitly address the nonnegativity constraint in the sampling model. The comparisons were carried out for data from two previously published studies, from different laboratories, on US-induced lung hemorrhage. The thresholds derived from logistic regression of lesion occurrence and tobit regression of lesion size were quite consistent with each other and within sampling error. The hockey stick thresholds, defined as the exposure level at which the piecewise linear model for the probability of the expected size of a lesion bends upward, corresponded to quite different excess risk values for incidence (lesion occurrence) compared with size (lesion surface area or depth), although these methods have been developed previously for both types of data. The use of probability-based excess risk thresholds is recommended to obtain consistent incidence vs. size thresholds and to ensure that the thresholds are well-defined and interpretable independent of the details of the statistical model.

Animals↗
PubMed2004

A highly Ca2+-sensitive pool of granules is regulated by glucose and protein kinases in insulin-secreting INS-1 cells.

We have used membrane capacitance measurements and carbon-fiber amperometry to assay exocytosis triggered by photorelease of caged Ca(2+) to directly measure the Ca(2+) sensitivity of exocytosis from the INS-1 insulin-secreting cell line. We find heterogeneity of the Ca(2+) sensitivity of release in that a small proportion of granules makes up a highly Ca(2+)-sensitive pool (HCSP), whereas the bulk of granules have a lower sensitivity to Ca(2+). A substantial HCSP remains after brief membrane depolarization, suggesting that the majority of granules with high sensitivity to Ca(2+) are not located close to Ca(2+) channels. The HCSP is enhanced in size by glucose, cAMP, and a phorbol ester, whereas the Ca(2+)-sensitive rate constant of exocytosis from the HCSP is unaffected by cAMP and phorbol ester. The effects of cAMP and phorbol ester on the HCSP are mediated by PKA and PKC, respectively, because they can be blocked with specific protein kinase inhibitors. The size of the HCSP can be enhanced by glucose even in the presence of high concentrations of phorbol ester or cAMP, suggesting that glucose can increase granule pool sizes independently of activation of PKA or PKC. The effects of PKA and PKC on the size of the HCSP are not additive, suggesting they converge on a common mechanism. Carbon-fiber amperometry was used to assay quantal exocytosis of serotonin (5-HT) from insulin-containing granules following preincubation of INS-1 cells with 5-HT and a precursor. The amount or kinetics of release of 5-HT from each granule is not significantly different between granules with higher or lower sensitivity to Ca(2+), suggesting that granules in these two pools do not differ in morphology or fusion kinetics. We conclude that glucose and second messengers can modulate insulin release triggered by a high-affinity Ca(2+) sensor that is poised to respond to modest, global elevations of [Ca(2+)](i).

Animals↗
PubMed2004

Mice carrying the szt1 mutation exhibit increased seizure susceptibility and altered sensitivity to compounds acting at the m-channel.

PURPOSE: Mutations in the genes that encode subunits of the M-type K+ channel (KCNQ2/KCNQ3) and nicotinic acetylcholine receptor (CHRNA4) cause epilepsy in humans. The purpose of this study was to examine the effects of the Szt1 mutation, which not only deletes most of the C-terminus of mouse Kcnq2, but also renders the Chnra4 and Arfgap-1 genes hemizygous, on seizure susceptibility and sensitivity to drugs that target the M-type K+ channel. METHODS: The proconvulsant effects of the M-channel blocker linopirdine (LPD) and anticonvulsant effects of the M-channel enhancer retigabine (RGB) were assessed by electroconvulsive threshold (ECT) testing in C57BL/6J-Szt1/+ (Szt1) and littermate control C57BL/6J+/+ (B6) mice. The effects of the Szt1 mutation on minimal clonic, minimal tonic hindlimb extension, and partial psychomotor seizures were evaluated by varying stimulation intensity and frequency. RESULTS: Szt1 mouse seizure thresholds were significantly reduced relative to B6 littermates in the minimal clonic, minimal tonic hindlimb extension, and partial psychomotor seizure models. Mice were injected with LPD and RGB and subjected to ECT testing. In the minimal clonic seizure model, Szt1 mice were significantly more sensitive to LPD than were B6 mice [median effective dose (ED50) = 3.4 +/- 1.1 mg/kg and 7.6 +/- 1.0 mg/kg, respectively]; in the partial psychomotor seizure model, Szt1 mice were significantly less sensitive to RGB than were B6 mice (ED50 = 11.6 +/- 1.4 mg/kg and 3.4 +/- 1.3 mg/kg, respectively). CONCLUSIONS: These results suggest that the Szt1 mutation alters baseline seizure susceptibility and pharmacosensitivity in a naturally occurring mouse model.

Animals↗
PubMed2004

Clinical experience with molecular adsorbent recirculating system (MARS) in patients with drug-induced liver failure.

The molecular adsorbent recirculating system (MARS) is a novel extracorporeal technique for liver support. We report the clinical results in a group of fourteen patients with drug-induced liver failure. Fourteen patients, aged 22-83 years, with acute or subacute liver failure [mean Child-Turcotte-Pugh (CTP) score 11 (range 8-15)] due to the intake of various drugs (diet pill overdose-2; Chinese traditional medicine (CTM)-4; antibiotic, paracetamol, tuberculostatic, or vasodilator abuse-8) were treated with one to seven sessions of MARS. Beneficial effects such as the improvement of encephalopathy and prothrombin activity, as well as a reduction of bilirubin and ammonia were recorded during MARS treatments. Thirteen out of fourteen patients survived the hospitalization (93%), and two of the discharged patients died during the follow-up of 6-12 months. The overall survival rate was about 79%. MARS therapy can contribute to the improved treatment of drug-induced liver failure patients.

Adult↗
PubMed2004

The intricate role of complement component C4 in human systemic lupus erythematosus.

It was observed about 50 years ago that low serum complement activity or low protein concentrations of complement C4 concurred with disease activities of systemic lupus erythematosus (SLE). Complete deficiencies of complement components C4A and C4B, albeit rare in human populations, are among the strongest genetic risk factors for SLE or lupus-like disease, across HLA haplotypes and racial backgrounds. However, whether heterozygous or partial deficiency of C4A (C4AQ0) or C4B (C4BQ0) is a predisposing factor for SLE has been a highly controversial topic. In this review we critically analyzed past epidemiologic studies on deficiency of C4A or C4B in human SLE. Cumulative results from more than 35 different studies revealed that heterozygous and homozygous deficiencies of C4A were present in 40-60% of SLE patients from almost all ethnic groups or races investigated, which included northern and central Europeans, Anglo-Saxons, Caucasians in the US, African Americans, Asian Chinese, Koreans and Japanese. In addition, French SLE and control populations had relatively low frequencies of C4AQ0, but the difference between the patient and control groups was statistically significant. The relative risk of C4AQ0 in SLE varied between 2.3 and 5.3 among different ethnic groups. In Caucasian and African SLE patients, the two major causes for C4AQ0 are (1) the presence of a mono-S RCCX (RP-C4-CYP21-TNX) module with a single, short C4B gene in the major histocompatibility complex; and (2) a 2-bp insertion into the sequence for codon 1213 at exon 29 of the mutant C4A gene. Both mono-S structures and 2-bp insertion in exon 29 are absent or extremely rare in the C4AQ0 of Oriental SLE patients. The highly significant association of C4AQ0 with SLE across multiple HLA haplotypes and ethnic groups, and the presence of different mechanisms leading to a C4A protein deficiency among SLE patients suggested that deficiency or low expression level of C4A protein is a primary risk factor for SLE disease susceptibility per se. On the other hand, Spanish, Mexican, Australian Aborigine SLE patients had increased frequencies of C4B deficiency instead of C4A deficiency. Such observations underscore the importance of both C4A and C4B proteins in the fine control of autoimmunity. Different racial and genetic backgrounds could change the thresholds for the requirement of C4A or C4B protein levels in immune tolerance and immune regulation. Most past epidemiological studies of C4 in human SLE did not consider the polygenic and gene size variations of C4A and C4B. In addition, many studies were overly dependent on phenotypic observations or methods that did not distinguish differential C4A and C4B protein expression caused by unequal gene number or different gene size from the absence of a functional C4A or C4B gene. For further longitudinal studies on clinical manifestations of SLE, it would be informative to stratify the patients with accurately defined C4A and C4B genotypes. Likewise, elucidation of epistatic genetic factors interacting with C4AQ0 would provide important insights into the intricate roles of C4 in SLE disease susceptibility and pathogenesis.

Alleles↗
PubMed2004

[Analyses of ultrasonographs of adrenal gland cysts in comparison with pathological findings].

OBJECTIVE: To investigate the value of ultrasonography in the diagnosis of adrenal gland cysts. METHODS: Six patients with adrenal gland cysts were examined by two-dimensional ultrasonography and color Doppler flow imaging (CDFI), and the results were compared with the pathological findings. RESULTS: The diagnoses by ultrasonography and CDFI were consistent with the pathological findings in 5 cases. CONCLUSION: Ultrasonography and CDFI can be an accurate diagnostic modality for adrenal gland cysts.

Adrenal Gland Diseases↗
PubMed2004

[Effect of coriaria lactone on the activation of Ca(2+)-activated K+ channel in hippocampal pyrimidal neurons of rats].

OBJECTIVE: This research sought to disclose the regulatory effect of Coriaria lactone (CL) on the Ca(2+)-activated K+ channel in hippocampal pyrimidal neurons of Wistar rats in epileptogenesis. METHODS: Cell-attached and inside-out methods of patch clamp technique were used to record the activity of single channel. The sample data were stored in a computer and analyzed by the application of Pclamp softwares. RESULTS: 1. By means of inside-out method, the KCa channels (120.34 +/- 25.12) pS on the membrane of hippocampal pyrimidal neurons showed a distinct dependence on calcium concentration (n = 6) and on voltage (n = 17), and the channels could be blocked by TEA. 2. With the use of cell-attached method, the KCa channels could be activated by CL apparently (n = 25, P < 0.01). 3. In the conditions where the neuronal membranous voltage was kept at 20 mV and the [Ca2+]i at 10(-8) mol/L in bath solution, the CL at concentrations from 0 microliter/ml to 1.0 microliter/ml could make the open state probability of KCa to increase from 0.025 to 0.553 (P < 0.01), the mean opening time (ms) to prolong from 1.875 +/- 0.412 to 6.829 +/- 0.136, and the mean closing time (ms) to decrease from 179.342 +/- 13.831 to 6.412 +/- 1.383 (n = 25, P < 0.01). CONCLUSION: The membranous KCa activation induced by CL may play an important negative feedback regulating role in the mechanism of epileptogenesis.

Animals↗
PubMed2004

[Detection of thrombus precursor protein and its clinical significance].

OBJECTIVE: To discuss the significance of the concentration change of plasma thrombus precursor protein (TpP) in the diagnosis of disseminated intravascular coagulation (DIC) or pre-DIC. METHODS: Enzyme linked immunosorbent assay (ELISA) was used in the detection of plasma TpP in patients with different diseases (77) and normal adults (47). At the same time, other correlated markers were detected and statistical comparison was proceeded. RESULTS: The concentration of TpP in the disease group (11.20 +/- 5.10) mg/L or the DIC (13.20 +/- 7.96) mg/L and non-DIC group (8.33 +/- 6.30) was obviously higher than that in the control group (1.29 +/- 1.02, P > 0.001). The concentration TpP in the DIC group was also obviously higher than that in the non-DIC group (P > 0.01). The rate of abnormal level of TpP in the DIC group was 100%, being higher than that of other markers related with DIC. CONCLUSION: Results of this study and pertinent literature showed that TpP detection has higher specificity and sensitivity than D-Dimer or fibrinogen (Fbg) assay in the diagnosis of DIC or pre-DIC. It provides more referable values for the diagnosis, treatment and prognosis of DIC.

Adult↗
PubMed2004

[Analysis on main factors for successful quitting--study on the one-year follow-up for Chinese 'Quit and Win' in 2002].

OBJECTIVE: China took part in the fifth 'Quit & Win in 2002 which was held by WHO and KTL in Finland. 27398 participants from eleven cities in China took part in the contest. Then we had a one-year follow-up research from May to June in 2003. METHODS: A random sample of 1298 was surveyed by mailing, telephone and visiting. RESULTS: One year were 27.71%. Main factors for successful quitting in one year included "intention to stop smoking completely by participating the contest", "age", "marriage", et al. But some factors had no effect on the successful quitting, such as cessation measures, helping from others, et al. CONCLUSION: It is important for smokers to make a decision and perseverance to stop smoking.

China↗
PubMed2003

Diversity in intrinsic strengths of the human complement system: serum C4 protein concentrations correlate with C4 gene size and polygenic variations, hemolytic activities, and body mass index.

Among the genes and proteins of the human immune system, complement component C4 is extraordinary in its frequent germline variation in the size and number of genes. Definitive genotypic and phenotypic analyses were performed on a central European population to determine the C4 polygenic and gene size variations and their relationships with serum C4A and C4B protein concentrations and hemolytic activities. In a study population of 128 healthy subjects, the number of C4 genes present in a diploid genome varied between two to five, and 77.4% of the C4 genes belonged to the long form that contains the endogenous retrovirus HERV-K(C4). Intriguingly, higher C4 serum protein levels and higher C4 hemolytic activities were often detected in subjects with short C4 genes than those with long genes only, suggesting a negative epistatic effect of HERV-K(C4) on the expression of C4 proteins. Also, the body mass index appeared to affect the C4 serum levels, particularly in the individuals with medium or high C4 gene dosages, a phenomenon that was dissimilar in several aspects from the established correlation between body mass index and serum C3. As expected, there were strong, positive correlations between total C4 gene dosage and serum C4 protein concentrations, and between serum C4 protein concentrations and C4 hemolytic activities. There were also good correlations between the number of long genes with serum levels of C4A, and the number of short genes with serum levels of C4B. Thus, the polygenic and gene size variations of C4A and C4B contribute to the quantitative traits of C4 with a wide range of serum protein levels and hemolytic activities, and consequently the power of the innate defense system.

Adult↗