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Yan Li

Publications and source records attributed to Yan Li.

At least 145 records · Page 8Linked to original sources

Ambulatory arterial stiffness index derived from 24-hour ambulatory blood pressure monitoring.

We hypothesized that 1 minus the slope of diastolic on systolic pressure during 24-hour ambulatory monitoring (ambulatory arterial stiffness index [AASI]) might reflect arterial stiffness. We compared AASI with established measures of arterial stiffness and studied its distribution in Chinese and European populations. We used 90207 SpaceLabs monitors and the SphygmoCor device to measure AASI, central and peripheral pulse pressures, the central (CAIx) and peripheral (PAIx) systolic augmentation indexes, and aortic pulse wave velocity. In 166 volunteers, the correlation coefficient between AASI and pulse wave velocity was 0.51 (P<0.0001). In 348 randomly recruited Chinese subjects, AASI correlated (P<0.0001) with CAIx (r=0.48), PAIx (r=0.50), and central pulse pressure (r=0.50). AASI increased with age and mean arterial pressure but decreased with body height. Both before and after adjustment for arterial wave reflections by considering height and heart rate as covariates, AASI correlated more (P<0.0001) closely with CAIx and PAIx than 24-hour pulse pressure. Among normotensive subjects, the 95th percentile of AASI was 0.55 in Chinese and 0.57 in 1617 Europeans enrolled in the International Database on Ambulatory Blood Pressure Monitoring. The upper boundary of the 95% prediction interval of AASI in relation to age ranged from 0.53 at 20 years to 0.72 at 80 years. In conclusion, AASI is a new index of arterial stiffness that can be easily measured under ambulatory conditions. Pending additional validation in outcome studies, normal values of AASI are probably <0.50 and 0.70 in young and older subjects, respectively.

Adolescent↗

Ambulatory arterial stiffness index as a predictor of cardiovascular mortality in the Dublin Outcome Study.

We hypothesized that the dynamic relation between diastolic and systolic blood pressure over 24 hours provides a measure of arterial stiffness and might, therefore, predict cardiovascular mortality over and above pulse pressure. At baseline, while not on antihypertensive medication, 11 291 patients (mean age, 54.6 years; 5965 women) underwent ambulatory blood pressure monitoring. Using all of the blood pressure readings, we plotted diastolic against systolic blood pressure from each individual and calculated the regression slope. The ambulatory arterial stiffness index (AASI) was defined as 1 minus this regression slope. Over a median follow-up of 5.3 years, 566 cardiovascular deaths occurred, including 151 from stroke and 358 from cardiac disorders. Before and after adjustment for other cardiovascular risk factors, AASI and pulse pressure significantly predicted total cardiovascular mortality. AASI was a stronger predictor than pulse pressure for stroke (mutually adjusted relative hazard ratios for 1 SD increase, 1.21 versus 1.04; P=0.02 versus 0.66) with the opposite trend for cardiac mortality (relative hazard ratios, 1.03 versus 1.21; P=0.63 versus 0.002). In subjects with normal daytime ambulatory blood pressure (<135/<85 mm Hg), AASI was more predictive than pulse pressure of cardiovascular mortality (1.26 versus 0.96; P=0.04 versus 0.70) and of stroke mortality (1.81 versus 1.12; P=0.007 versus 0.58), whereas neither independently predicted cardiac mortality (1.11 versus 0.89; P=0.47 versus 0.40). AASI is a novel measure of arterial stiffness, which can be readily determined from ambulatory blood pressure recordings and which independently predicts cardiovascular mortality, even in normotensive subjects.

Adult↗

Apoptosis of HL-60 cells induced by extracts from Narcissus tazetta var. chinensis.

Narcissus tazetta var. chinensis is one member of the Amaryllidaceae family. We found that extracts from N. tazetta var. chinensis (ENT) strongly decreased the survival rate of the following tumor cell lines: HL-60, K562, KT1/A3, and A3R. The cytotoxic effects of ENT on non-cancer cells lines (NHBE and NIH3T3) were smaller than on leukemia cell lines. AO/EB staining and flow cytometry assays showed that ENT induced HL-60 cell apoptosis. Furthermore, the release of cytochrome c and the increase of caspase-8, -9, and -3 activities were tested after HL-60 cells were treated with ENT, which indicated that the mitochondrial pathway and cell death receptor pathway were both involved in the apoptosis signal pathways induced by ENT. Upregulation of Bax showed that the Bcl-2 family was involved in the control of apoptosis. Our results suggest that apoptosis activity can be mediated by ENT in HL-60 cells.

Antineoplastic Agents↗

Synchrotron microradiography study on acute lung injury of mouse caused by PM(2.5) aerosols.

In order to investigate FeSO(4), ZnSO(4) (the two of main metal compositions of Shanghai PM(2.5) (particle matter with those aerodynamical diameter <2.5 microm)) effects on acute lung injury, six solutions contained PM(2.5) aerosol particles, FeSO(4), ZnSO(4) and their mixtures were instilled intratracheally into mouse lungs for experiment. By 2 days after instillation, the live mice were checked in vivo by synchrotron refractive index microradiography. In addition after extracted and examined by dissection, the right lobes of lung were fixed by formalin, then imaged by synchrotron microradiography again. Corresponding parts of those lung tissues were embedded in paraffin for histopathologic study. The synchrotron X-ray microradiographs of live mouse lung showed different lung texture changes after instilled with different toxic solutions. Hemorrhage points in lung were observed more from those mice instilled by FeSO(4) contained toxin solutions groups. Bronchial epithelial hyperplasia can be observed in ZnSO(4) contained solution-instilled groups from histopathologic analysis. It was found that the acute lung injury of mice caused by solution of PM(2.5)+FeSO(4)+ZnSO(4) was more serious than other toxin solutions. Results suggested that FeSO(4) mainly induced hemorrhage and ZnSO(4) mainly induced inflammation and bronchiolar epithelial hyperplasia in the early toxicological effects of PM(2.5).

Aerosols↗

Substantia nigra tangles are related to gait impairment in older persons.

OBJECTIVE: Parkinsonian signs, especially gait impairment, are common and associated with morbidity and mortality in older persons. Our objective was to test the hypothesis that substantia nigra neurofibrillary tangles (NFTs) are related to parkinsonian signs in older persons with and without dementia. METHODS: We studied 86 deceased older Catholic clergy without idiopathic Parkinson's disease from the Religious Order Study, a longitudinal clinical-pathological study. Mean age at death was 85.3 years. Signs of gait disturbance, bradykinesia, rigidity, and tremor were assessed proximate to death using a modified Unified Parkinson's Disease Rating Scale. Forty-micrometer paraffin-embedded sections of substantia nigra were bleached before tau immunohistochemistry and the optical disector was used to count NFTs. We used multivariable linear regression to examine parkinsonian signs as a function of nigra NFTs, controlling for age, sex, education, and cortical NFTs. RESULTS: Substantia nigra NFTs were present in 67 of 86 persons (77.9%). After controlling for age, sex, education, and cortical NFTs, nigra NFTs were related to gait impairment (p < 0.001), but not bradykinesia, rigidity, or tremor. Results were not confounded by dementia, Braak score, neuroleptic medication, cerebral infarcts, or Lewy bodies. INTERPRETATION: NFTs in the substantia nigra are associated with gait impairment in older persons with and without dementia.

Aged, 80 and over↗

Remodeling dynamics in the alveolar process in skeletally mature dogs.

Bone turnover rates can be altered by metabolic and mechanical demands. Due to the difference in the pattern of loading, we hypothesized that there are differences in bone remodeling rates between the maxillary and mandibular alveolar processes. Furthermore, in a canine model, the alveolar process of teeth that lack contact (e.g., second premolars) would have a different turnover rate than bone supporting teeth with functional contact (e.g., first molars). Six skeletally mature male dogs were given a pair of calcein labels. After sacrifice, specimens representing the anterior and posterior locations of both jaws were prepared for examination by histomorphometric methods to evaluate the bone volume/total volume (BV/TV; %), bone volume (mm2), mineral apposition rate (MAR; microm/day), and bone formation rate (BFR; %/year) in the alveolar process. There were no significant differences (P>0.05) in the BV/TV within the jaws. The bone volume within the alveolar process of the mandible was 2.8-fold greater than in the maxilla. The MAR was not significantly different between the jaws and anteroposterior locations. However, the BFR was significantly (P<0.0001) greater in the mandible than in the maxilla. The anterior location had higher (P=0.002) remodeling than the posterior location in the maxilla but not in the mandible. While there was a greater bone mass and increased remodeling in the mandible, no remodeling gradient in the coronal-apical direction was apparent in the alveolar process. Bone adaptation probably involves a complex interplay of bone turnover, mass, and architecture.

Alveolar Process↗

Requirement of reversible caldesmon phosphorylation at P21-activated kinase-responsive sites for lamellipodia extensions during cell migration.

Caldesmon is believed to be one of the key regulators for actin dynamics and thereby cell polarity, membrane extension, and cell motility. We have shown previously that stress fiber formation and cell movement are severely impaired in the cells expressing human fibroblast caldesmon fragment defective in Ca2+/CaM binding sites. Both Ser458 and Ser489, adjacent to the Ca2+/CaM-binding sites, are phosphorylated by p21-activated kinase (PAK) in vitro. Here we report that Ser458 is phosphorylated in response to cell movement. We substituted Ser458 and Ser489 on C-terminal caldesmon (CaD39) with alanine or glutamic acid to mimic under-phosphorylated (CaD39-PAKA) or constitutively phosphorylated (CaD39-PAKE) caldesmon. In vitro, CaD39-PAKE, but not CaD39-PAKA, fails to inhibit myosin ATPase activity and exhibits reduced binding to Ca2+/CaM. When stably expressed in Chinese Hamster Ovary cells, both CaD39-PAKA and CaD39-PAKE incorporate into stress fibers and localize to the leading edge of the migrating cell. Expression of CaD39-PAKE, but not CaD39-PAKA, fails to protect stress fibers from cytochalasin depolymerization. However, both mutations inhibit cell polarization and lead to defects in membrane extension and cell migration. We conclude that phosphorylation of caldesmon by PAK is a dynamic process required to regulate actin dynamics and membrane protrusions in wound-induced cell migration.

Alanine↗

Comprehensive two-dimensional separation in coupling of reversed-phase chromatography with capillary isoelectric focusing followed by MALDI-MS identification using on-target digestion for intact protein analysis.

A coupling of capillary RP LC as the first dimension with CIEF as the second dimension followed by MALDI-MS identification was demonstrated. Based on 2-D separation system developed by our group (Electrophoresis 2003, 24, 3289-3295), this paper focused on incorporating tryptic digestion into the top-down proteomics methodology, retaining the benefits of the top-down method. Hydrophobic layer of packing-material C18 coated with SE-30 on the MALDI-target surface was used to permit the CIEF fractions to be easily concentrated and free of ampholytes using on-target washing. Following the removal of ampholytes, on-target tryptic digestion was performed to generate PMF for protein identification. Using the proteome analytical strategy, we could obtain not only intact protein pI value but also PMF for accurate protein identification. The feasibility of the strategy was first tested with a mixture of model proteins with different pIs and molecular masses. Proteome of rat liver tissue extracts was further analyzed using the system for verification. The results have shown that the system is effective for complex proteomic analysis.

Animals↗

Cognitive decline and survival in Alzheimer's disease.

OBJECTIVE: To test the association of rate of cognitive decline, an indicator of the severity of the underlying disease process, with risk of death in Alzheimer's disease (AD). METHODS: A total of 472 persons with clinically diagnosed AD were recruited from a memory disorders clinic and day care centers in the Chicago area. They completed a uniform clinical evaluation at baseline and a battery of nine cognitive tests at six-month intervals for a mean of about three years. A previously established measure of global cognition was derived from the nine tests. RESULTS: During follow-up, 168 persons (36%) died. In a proportional hazards model that controlled for age, sex, race, education, and baseline level of cognition, individual rate of global cognitive decline, estimated with least squares regression, was linearly related to mortality risk. Thus, a person declining minimally (increase of 0.04 unit per year, 90th percentile) was 2.7 times less likely to die during the study period than a person declining rapidly (decrease of 0.76 unit per year, 10th percentile). Controlling for baseline disability did not substantially affect results. The association of cognitive decline with mortality was substantially stronger for white persons compared to African Americans and in those with less compared to more education. CONCLUSION: The results indicate that the rate at which cognition declines in AD is robustly related to survival.

Adult↗

Modulation of protein release from biodegradable core-shell structured fibers prepared by coaxial electrospinning.

Biodegradable core-shell structured fibers with poly(epsilon-caprolactone) as shell and bovine serum albumin (BSA)-containing dextran as core were prepared by coaxial electrospinning for incorporation and controlled release of proteins. BSA loading percent in the fibers and its release rate could be conveniently varied by the feed rate of the inner dope during electrospinning. With the increase in the feed rate of the inner dope, there was an associated increase in the loading percent and accelerated release of BSA. Poly(ethylene glycol) (PEG) was added to the shell section of the fibers to further finely modulate the release behavior of BSA. It was revealed that the release rate of BSA increased with the PEG percent in the shell section. By varying the feed rate of the inner dope and PEG content, most of BSA could be released from the core-shell structured fibers within the period of time ranging from 1 week to more than 1 month. The effect of the feed rate of the inner dope and addition of PEG into the shell section on the fiber morphology was also examined by scanning electron microscope.

Absorbable Implants↗

Association of genetic polymorphism of low-density lipoprotein receptor with chronic viral hepatitis C infection in Han Chinese.

To study the association between the Ava II polymorphism at the low-density lipoprotein receptor (LDL-R) gene exon 13 locus and chronic hepatitis C virus (HCV) infection in the Han Chinese, 84 chronic HCV-infected patients without anti-viral treatment, and 72 healthy blood donors were studied. Polymerase chain reaction combined with restriction fragment length polymorphism (PCR-RFLP) was used to detect the Ava II polymorphism at the LDL-R gene exon 13 locus. The comparisons of genotype distribution and allele frequency between chronic HCV-infected patients and healthy controls showed statistically significant differences (P = 0.045 and P = 0.036, respectively). Additionally, the minor allele frequency (MAF) C in the healthy controls was higher than that in the chronic HCV-infected patients group. There was no significant difference (P = 0.130) when the genotype distribution was compared between chronic HCV-infected patients with HCV viremia and those without HCV viremia. However, the comparisons of allele frequency between the two groups showed a statistically significant difference (P = 0.047), and the MAF C in HCV RNA negative group was significantly higher than that in HCV RNA positive group. There were no significant differences in genotype distribution and allele frequency of the Ava II restriction site at the LDL-R gene exon 13 locus between patients with chronic HCV infection and those with HCV-associated cirrhosis as well as between patients with normal serum alanine aminotransferase (ALT) and those with abnormal ALT levels. These results suggest that the Han Chinese have Ava II polymorphism at the LDL-R gene exon 13 locus. The Ava II polymorphism at the LDL-R gene exon 13 locus showed a statistically significant difference between chronic HCV-infected patients and healthy controls, indicating a significant contribution of the Ava II polymorphism in susceptibility to HCV infection in these patients. The MAF C in HCV RNA negative group was higher than that in HCV RNA positive group, suggesting that the Ava II polymorphism might also be associated with viremia in patients with HCV infection.

Adult↗

Expression of Myh9 in the mammalian cochlea: localization within the stereocilia.

Mutations of non-muscle myosin Type IIA or MYH9 are linked to syndromic or nonsyndromic hearing loss. The biologic function of MYH9 in the auditory organ and the pathophysiology of its dysfunction remain to be determined. The mouse represents an excellent model for investigating the biologic role of MYH9 in the cells and tissues affected by its dysfunction. A primary step toward the understanding of the role of MYH9 in hearing and its dysfunction is the documentation of its cellular and sub-cellular localization within the cochlea, the auditory organ. We describe the localization of Myh9 within the mouse cochlea using a polyclonal anti-Myh9-antibody, generated against an 18 amino acid long peptide corresponding to the sequence at the C-terminus of mouse Myh9. The anti-Myh9 antibody identified a single, specific, immunoreactive band of 220 kDa in immunoblot analysis of homogenate from a variety of different mouse tissues. The Myh9 antibody cross-reacts with the rat but not the human orthologue. Myh9 is expressed predominantly within the spiral ligament as well as in the sensory hair cells of the organ of Corti. Confocal microscopy of cochlear surface preparations, identified Myh9 within the inner and outer hair cells and their stereocilia. Localization of Myh9 within the stereocilia raises the possibility that mutations of MYH9 may effect hearing loss though disruption of the stereocilia structure.

Animals↗

Array based capillary IEF with a whole column image of laser-induced fluorescence in coupling to capillary RPLC as a comprehensive 2-D separation system for proteome analysis.

Based on array CIEF (ACIEF) and a novel whole column imaging detection (WCID), a comprehensive 2-D system with laser-induced fluorescence was developed for protein mapping. By coupling capillary RPLC (CRPLC) as the first dimension and ACIEF as the second dimension, a high-throughput and high-resolution proteomic expression profiling was obtained. An array of up to 60 capillaries was assembled, with electrical connections made through filling small breaks, created on each capillary at positions of buffer reservoirs, with a porous polymer. A whole column image system with laser-induced fluorescence (LIF) was devised. Spot excitation was performed with a laser converted to produce linear light, and a CCD camera was employed to take images of the protein fluorescence during line laser scanning of the capillary array. Quantitative detection of thousands of focusing protein bands in the capillary array was achieved. Details on the capillary array fabrication and scanning LIF detection system devices are discussed. The efficiency of this CRPLC-ACIEF-LIF-WCID system was further demonstrated using samples of soluble proteins extracted from liver cancer tissue. The overall peak capacity was estimated to be around 18 000 in an analysis time of less than 3 h. The reproducibility of consecutive runs and different columns were assessed as having an RSD of 1.5% and 2.2% in focusing positions, respectively.

Animals↗

An alternative strategy for high throughput generation and characterization of monoclonal antibodies against human plasma proteins using fractionated native proteins as immunogens.

Construction of a monoclonal antibody (mAb) bank containing a vast variety of antibodies against human tissue proteins is important for proteomic research. A novel strategy of subtractive immunization using fractionated native proteins was developed for high throughput generation of mAb against human plasma proteins. By this novel approach, the bottleneck of antigen preparation can be overcome by combining repeated immunization of animals with subtracted fractions of plasma or tissue proteins and identification of target antigen by immunoprecipitation/mass spectrum strategies. Plasma freshly collected from healthy adults was pooled and three fractions were prepared by size exclusion chromatography. Mice were immunized with the fractionated plasma proteins, and 205 strains of hybridomas secreting mAb were obtained after two-round subtractive immunizations and cell fusions. In the first round, 110 strains of hybridomas were established, in which 77 strains secreting mAb were identified against 10 human plasma high-abundant proteins. In the second round, plasma fraction I was absorbed with mAb against IgM, IgG, ceruloplasmin and haptoglobin. The absorbed fraction I was used as immunogen for the second round immunization and cell fusion. Ninety-five strains of hybridomas secreting mAb were obtained. Although the target antigens of mAb from 82 strains of hybridomas were identified as IgM, IgA, alpha2-macroglobulin and fibrinogen, about 85% antibodies obtained from this round were identified as new antibodies when compared with mAb obtained in the first round immunization with plasma fraction I. The results suggest that subtractive immunization with fractionated plasma proteins followed by identification of antigens with immunoprecipitation/mass spectrum may be an effective approach for rapid preparation of mAb against high-and medium-abundant plasma or tissue proteins.

Amino Acid Sequence↗

Optimized proteomic analysis of a mouse model of cerebellar dysfunction using amine-specific isobaric tags.

Recent proteomic applications have demonstrated their potential for revealing the molecular mechanisms underlying neurodegeneration. The present study quantifies cerebellar protein changes in mice that are deficient in plasma membrane calcium ATPase 2 (PMCA2), an essential neuronal pump that extrudes calcium from cells and is abundantly expressed in Purkinje neurons. PMCA2-null mice display motor dyscoordination and unsteady gait deficits observed in neurological diseases such as multiple sclerosis and ataxia. We optimized an amine-specific isobaric tags (iTRAQ)-based shotgun proteomics workflow for this study. This workflow took consideration of analytical variance as a function of ion signal intensity and employed biological repeats to aid noise reduction. Even with stringent protein identification criteria, we could reliably quantify nearly 1000 proteins, including many neuronal proteins that are important for synaptic function. We identified 21 proteins that were differentially expressed in PMCA2-null mice. These proteins are involved in calcium homeostasis, cell structure and chromosome organization. Our findings shed light on the molecular changes that underlie the neurological deficits observed in PMCA2-null mice. The optimized workflow presented here will be valuable for others who plan to implement the iTRAQ method.

Amines↗

A novel external esophageal perfusion model for reflux esophageal injury.

The current animal models of esophagitis and Barrett's esophagus consist of surgeries that divert the gastroduodenal contents to the esophagus. The limitations of these models are the inability to control the amount and concentration of the refluxate and the causing of significant postoperative stress and morbidity. Eighteen adult rats were cannulated at the upper esophagus and connected to a subcutaneous osmotic micropump to perfuse the esophageal lumen with bile and acid. Animals were sacrificed after 7 days of perfusion. Histological changes were determined. Cell proliferation, apoptosis, lipid peroxidation, and glutathione were measured. Histopathological changes in the bile- or acid-perfused esophagus were consistent with the findings associated with reflux esophagitis. Enhanced proliferation and apoptosis were seen, along with increased oxidative stress. The external esophageal perfusion model enabled precise control of the injurious agent. It induced the histologic and cellular injury of reflux esophagitis after 7 days.

Acetic Acid↗

Production of porcine cloned transgenic embryos expressing green fluorescent protein by somatic cell nuclear transfer.

In the present study, nuclear transferred embryos (NTEs) were reconstructed by using pig fetal fibroblasts as donors and in vitro matured oocytes as recipients. The effects of G418 selection on donor cells, duration of IVM of prepubertal gilt oocytes and oxygen tension in IVM of oocytes were investigated. The results were as follows: (i) When G418 selected cells expressing GFP were used as donors, the cleavage rate of NTEs decreased drastically in comparison to NTEs derived from donors without antibiotic selection (47.5% vs. 71.6%, p < 0.05). For the blastocyst rate, no significant difference was observed between two groups (10% vs. 10.4%, p > 0.05). (ii) The rate of nuclear maturation of oocytes increased significantly when IVM duration time was extended from 36 to 42 h (83.6% vs. 96.7%, p < 0.05). However, no statistical difference was observed between NTEs derived from oocytes of 36 h IVM group and NTEs from oocytes of 42 h IVM group in the rates of cleavage (59.3% vs. 73.6%, p > 0.05) and blastocyst formation (9.3% vs. 13.2%, p > 0.05); (iii) no significant difference was observed between NTEs reconstructed from oocytes matured under lower oxygen (7% O2) tension and NTEs derived from oocytes matured under higher oxygen tension (20% O2) in cleavage rate (70.6% vs. 67.1%, p > 0.05) and blastocyst rate (11.8% vs. 12.3%, p > 0.05). These results suggest that: (i) G418 selection does not have a significant effect on cleavage rate of NTEs expressing GFP. (ii) Nuclear maturation is greatly improved by prolonging IVM duration from 36 to 42 h, while no significant differences were observed for developmental potential of transgenic embryos. Thus IVM 42 h is the better choice in order to obtain maximum number of M II oocytes as recipients. (iii) Lower oxygen tension and higher oxygen tension in IVM have no significant effect on development of cloned embryos.

Animals↗