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Biomedical subjects

Lin Wang

Publications and source records attributed to Lin Wang.

At least 289 records · Page 16Linked to original sources
PubMed2002

PYPAF1, a PYRIN-containing Apaf1-like protein that assembles with ASC and regulates activation of NF-kappa B.

The PYRIN domain is a recently identified protein-protein interaction domain that is found at the N terminus of several proteins thought to function in apoptotic and inflammatory signaling pathways. We report here that PYPAF1 (PYRIN-containing Apaf1-like protein 1) is a novel PYRIN-containing signaling protein that belongs to the nucleotide-binding site/leucine-rich repeat (NBS/LRR) family of signaling proteins. The expression of PYPAF1 is highly restricted to immune cells, and its gene maps to chromosome 1q44, a locus that is associated with the rare inflammatory diseases Muckle-Wells syndrome and familial cold urticaria. To identify downstream signaling partners of PYPAF1, we performed a mammalian two-hybrid screen and identified ASC as a PYRIN-containing protein that interacts selectively with the PYRIN domain of PYPAF1. When expressed in cells, ASC recruits PYPAF1 to distinct cytoplasmic loci and induces the activation of NF-kappaB. Furthermore, coexpression of PYPAF1 with ASC results in a potent synergistic activation of NF-kappaB. These findings suggest that PYPAF1 and ASC function as upstream activators of NF-kappaB signaling.

Amino Acid Sequence↗
PubMed2002

Experimental study of the effect of autonomic nervous system on the transmural dispersion of ventricular repolarization under acute myocardial ischemia in vivo.

The effect of the autonomic nerves on the transmural dispersion of ventricular repolarization (TDR) under acute myocardial ischemia in intact canine was investigated. Using the monophasic action potential (MAP) recording technique, MAPs of the epicardium (Epi), mid-myocardium (Mid) and endocardium (Endo) were recorded simultaneously by specially designed plunge-needle electrodes at the left ventricular free wall under acute myocardial ischemia in 12 open-chest dogs. MAPD90 and TDR among three myocardial layers as well as the incidence of the early afterdepolarization (EAD) before autonomic nervous stimulation and during autonomic nervous stimulation were compared. It was found that 10 min after acute myocardial ischemia, TDR was increased from 55 +/- 8 ms to 86 +/- 15 ms during sympathetic stimulation (P < 0.01). The TDR (53 +/- 9 ms) during parasympathetic stimulation was not significantly different from that of the control (55 +/- 8 ms) (P > 0.05). The EAD was elicited in the Mid of 2 dogs (16%) 10 min after acute myocardial ischemia, but the EAD were elicited in the Mid of 7 dogs (58%) during sympathetic stimulation (P < 0.01). It was concluded that: (1) Sympathetic stimulation can increase the transmural dispersion of repolarization and induce early afterdepolarizations in the Mid under acute myocardial ischemia, which provide the opportunity for the ventricular arrhythmia developing; (2) Parasympathetic stimulation has no significant effect on the transmural dispersion of repolarization under myocardial ischemia.

Action Potentials↗
PubMed2002

Exponential stability of Cohen-Grossberg neural networks.

Exponential stabilities of the Cohen-Grossberg neural network with and without delays are analyzed. By Liapunov functions/functionals, sufficient conditions are obtained for general exponential stability, while by using a comparison result from the theory of monotone dynamical systems, componentwise exponential stability is also discussed. All results are established without assuming any symmetry of the connection matrix, and the differentiability and monotonicity of the activation functions.

Neural Networks, Computer↗
PubMed2002

Nuclear factor-kappaB and TNF-alpha mediate gastric ulceration induced by phorbol myristate acetate.

Phorbol esters induce inflammation in rodents by activating protein kinase C. We determined whether nuclear factor-kappaB (NF-kappaB) and tumor necrosis factor-alpha (TNF-alpha) play role in the formation of gastric ulcer induced by phorbol-12-myristate-13-alphacetate (PMA) in rats. Subserosally injected PMA dose-dependently induced gastric mucosal ulcer. Activation of NF-kappaB in the gastric mucosa corresponding to the PMA injection sites was observed before the ulcers became obvious as assessed by an in situ fluorescence DNA binding assay and electrophoretic mobility shift assay. The NF-kappaB activation and subsequent ulcer formation were significantly inhibited by injection of pyrrolidine dithiocarbamate, proteasome inhibitor (MG132), or NF-kappaB decoy. Antibody against TNF-alpha significantly inhibited ulcer formation without attenuating NF-kappaB activation. These results suggest that both NF-kappaB activation followed by TNF-alpha release contribute to tissue damage in PMA-induced gastric ulcer formation.

Animals↗
PubMed2002

Factors affecting the use of multifocal electroretinography to monitor function in a primate model of glaucoma.

While elevated intraocular pressure (IOP) undoubtedly plays a crucial role in many glaucoma patients, vascular dysregulation and chronic regional ischemia are also thought to contribute to the pathophysiology of glaucoma. In an effort to critically evaluate hypotheses involving vascular abnormalities in glaucoma, Cioffi, Van Buskirk and co-workers have developed a model of optic neuropathy based on chronic regional ischemia. The multifocal electroretinogram (MERG) has previously been used to assess function in non-human primates with experimental glaucoma induced by high-IOP. In this study, the MERG was used to monitor function in macaque monkeys with experimental glaucoma induced by chronic anterior optic nerve ischemia. Initial recordings from experimental eyes, which were later documented histologically to have moderate axon loss, revealed little difference from recordings of control eyes. This suggested that many of the signal components in the macaque MERG, which are known (from other studies) to be eliminated by intravitreal injections of NMDA/TTX or by high-IOP experimental glaucoma, may also be affected by the choice of anesthetic agents and MERG recording parameters. Subsequent experiments were performed to specifically evaluate the effects of bipolar versus monopolar signal derivation, anesthetic agents, MERG stimulus design and spatial scale. The results demonstrate that successful measurement of inner retinal and optic nerve head MERG components, especially those which have been shown by other investigators to originate with ganglion cell spiking activity, will depend critically upon the choice of anesthetic agents and recording parameters. One of the most important parameters seems to be use of a monopolar signal derivation, with the contralateral cornea serving as the reference position.

Anesthesia, General↗
PubMed2002

Sample survey of drug-resistant tuberculosis in Henan, China, 1996.

BACKGROUND: There is little reliable data on the global drug resistance to tuberculosis (TB) as most of the existing data is based upon biased samples, is not standardized or was obtained using poor techniques. For this reason, the World Health Organization (WHO) and the International Union Against Tuberculosis and Lung Disease (IUATLD) developed a global project on anti-TB drug resistance surveillance (DRS) in 1994. China joined this project in 1995 and the province of Henan was selected as the first site for collection of representative samples to survey the prevalence of drug-resistant TB. METHODOLOGY: Standard drug susceptibility testing by the proportion method against streptomycin (S), isoniazid (H), rifampicin (R), and ethambutol (E) was performed with Mycobacterium tuberculosis isolated from 916 new cases and 456 previously treated cases. Treatment outcome of these patients has been evaluated according to the regimens and drug susceptibility patterns. RESULTS: Drug resistance among new cases to any drug was found to be 43.0% and any resistance: S, 32.5%; H, 31.0%; R, 20.7%; and E, 10.3%. Drug resistance among previously treated cases to any drug was 68.2% and any resistance: S, 52.2%; H, 49.3%; R, 48.3%; and E, 20.4%. The cure rate for new cases was 43.3% and 29.4% for previously treated cases. The poor cure rate resulted mainly from a high defaulter rate. CONCLUSION: Drug-resistant TB was found to be highly prevalent in Henan and the cure rate remained poor. The results strongly indicated that Henan should take immediate action to improve the cure rate of patients through expansion of the introduction of the directly observed treatment short-course strategy.

Adult↗
PubMed2002

Ursodeoxycholic acid diminishes Fas-ligand-induced apoptosis in mouse hepatocytes.

Ursodeoxycholic acid (UDCA) can protect hepatocytes from apoptosis induced by a variety of stimuli including anti-Fas antibody. However, in vivo the Fas receptor is activated by its natural ligand, Fas-L, whereas anti-Fas antibodies are not a physiologic stimulus. We therefore have assessed the anti-apoptotic effects of UDCA and other bile acids in a novel coculture model where apoptosis is induced in murine hepatocytes by membrane-bound Fas-L expressing fibroblasts. Primary hepatocytes were cultured overnight on collagen-coated coverslips with increasing concentrations of different bile acids and overlaid with either NIH 3T3 Fas-L(+) or Fas-L(-) expressing fibroblasts. After 6 hours cells were fixed and apoptosis was evaluated by TUNEL assay and DAPI staining using digital imaging. Fas-L protein expression and Fas trimerization were evaluated by Western blot analysis. FITC-UDCA and Mitotracker Red were used to evaluate UDCA localization with mitochondria. UDCA (up to 100 micromol/L, P <.0001), TUDCA (up to 400 micromol/L, P <.0001), and TCDCA (up to 200 micromol/L, P <.0001), but not TCA (up to 500 micromol/L), significantly protected hepatocytes in Fas-L(+) cocultures. UDCA had no significant effect on hepatocytes in Fas-L(-) cocultures. TUDCA, 50 micromol/L (P <.001) and TCDCA up to 200 micromol/L (P <.0001) also reduced the hepatocytes apoptotic rate in Fas-L(-) cocultures. Bile acids did not affect Fas-L expression in fibroblasts or Fas trimerization. FITC-UDCA colocalized with the mitochondrial probe. In conclusion, UDCA, TUDCA, and TCDCA but not TCA are capable of protecting hepatocytes from Fas-L-induced apoptosis. This protective effect is not associated with reductions in Fas trimerization, but may be related to a direct effect on the mitochondrial membrane.

3T3 Cells↗
PubMed2002

Repression of telomerase activity during in vitro differentiation of osteosarcoma cells.

In this report, we studied the relationship between telomerase activity and in vitro differentiation of osteosarcoma cells. Human osteosarcoma cells (HOS-8603) were treated with all-trans-retinoic acid (RA) and dexamethasone (DEX). Cell cycle phase, alkaline phosphatase (AP) activity, telomerase activity, and human telomerase RNA (hTR) in treated cells were detected. The results showed that the treated cells underwent morphologic differentiation. AP activity of the cells increased significantly. The proportion of the cells in S and G2/M phases was increased. A pronounced decline in telomerase activity was observed, but no significant difference in the amount of hTR expressed, when compared with the control. This study demonstrates that: (1) both RA and DEX can inhibit cell growth and induce morphologic and functional differentiation of HOS-8603 cells; (2) telomerase is an enzyme system regulated during induced differentiation of HOS-8603 cells; (3) significantly decreased telomerase activity may be an indicator of differentiation but does not parallel the expression level of hTR; and (4) the regulation of telomerase is directly linked to cell differentiation not cell cycle.

Alkaline Phosphatase↗
PubMed2002

Characterization of a silicon-based shear-force sensor on human subjects.

A silicon sensor is developed and its ability to measure both compressive and shear forces at the skin-object interface is characterized. The sensor is designed based on the piezoresistive effect and fabricated using integrated circuit and microelectromechanical systems technologies. The sensor utilizes a mesa structure that leads to asymmetric diaphragm deformations in response to nonnormal loading. Four independent ion-implanted piezoresistors are used to detect the stresses induced in diaphragm and resolve both the compressive- and shear-force components. The sensor is calibrated on human subjects over a range of applied force (5- to 40-N shear force at increments of 1.25 N; 0- to 30-N compressive force). Force measurement via a tracking experiment is evaluated at four shear (9, 18, 25, and 35 N) and three compressive (7, 15, and 26 N) force levels. The sensor has good repeatability (SD approximately 1.7 N) with an average error of 12.1%.

Equipment Design↗
PubMed2002

Prediction of joint moments using a neural network model of muscle activations from EMG signals.

Because the relationship between electromyographic (EMG) signals and muscle activations remains unpredictable, a new way to determine muscle activations from EMG signals by using a neural network is proposed and realized. Using a neural network to predict the muscle activations from EMG signals avoids establishing a complex mathematical model to express the muscle activation dynamics. The feed-forward neural network model of muscle activations applied here is composed of four layers and uses an adjusted back-propagation training algorithm. In this study, the basic back-propagation algorithm was not applicable, because muscle activation could not be measured, and hence the error between predicted activation and the real activation was not available. Thus, an adjusted back-propagation algorithm was developed. Joint torque at the elbow was calculated from the EMG signals of ten flexor and extensor muscles, using the neural network result of estimated activation of the muscles. Once muscle activations were obtained, Hill-type models were used to estimate muscle force. A musculoskeletal geometry model was then used to obtain moment arms, from which joint moments were determined and compared with measured values. The results show that this neural network model can be used to represent the relationship between EMG signals and joint moments well.

Action Potentials↗
PubMed2002

The role of bile salt export pump mutations in progressive familial intrahepatic cholestasis type II.

PFIC II is a subtype of progressive familial intrahepatic cholestasis (PFIC) that is associated with mutations in the ABCB11 gene encoding the bile salt export pump (BSEP). However it is not known how these mutations cause this disease. To evaluate these mechanisms, we introduced seven PFIC II-associated missense mutations into rat Bsep and assessed their effects on Bsep membrane localization and transport function in MDCK and Sf9 cells, respectively. Five mutations, G238V, E297G, G982R, R1153C, and R1268Q, prevented the protein from trafficking to the apical membrane, and E297G, G982R, R1153C, and R1268Q also abolished taurocholate transport activity, possibly by causing Bsep to misfold. Mutation C336S affected neither Bsep transport activity nor the apical trafficking of Bsep, suggesting that this mutation alone may not cause this disease. D482G did not affect the apical expression but partially decreased the transport activity of Bsep. Mutant G238V was rapidly degraded in both MDCK and Sf9 cells, and proteasome inhibitor resulted in intracellular accumulation of this and other mutants, suggesting proteasome-mediated degradation plays an important role in expression of these PFIC II mutants. Our studies highlight the heterogeneous nature of PFIC II mutations and illustrate the significance of these mutations in the function and expression of Bsep.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2002

Distinct but conserved functions for two chloroplastic NADP-malic enzyme isoforms in C3 and C4 Flaveria species.

In the most common C4 pathway for carbon fixation, an NADP-malic enzyme (NADP-ME) decarboxylates malate in the chloroplasts of bundle sheath cells. Isoforms of plastidic NADP-ME are encoded by two genes in all species of Flaveria, including C3, C3-C4 intermediate, and C4 types. However, only one of these genes, ChlMe1, encodes the enzyme that functions in the C4 pathway. We compared the expression patterns of the ChlMe1 and ChlMe2 genes in developing leaves of Flaveria pringlei (C3) and Flaveria trinervia (C4) and in transgenic Flaveria bidentis (C4). ChlMe1 expression in C4 species increases in leaves with high C4 pathway activity. In the C3 species F. pringlei, ChlMe1 expression is transient and limited to early leaf development. In contrast, ChlMe2 is expressed in C3 and C4 species concurrent with stages in chloroplast biogenesis. Because previous studies suggest that NADP-ME activities generally reflect the level of its mRNA abundance, we discuss possible roles of ChlMe1 and ChlMe2 based on these expression patterns.

Asteraceae↗
PubMed2002

Immunohistologic evidence for retinal glial cell changes in human glaucoma.

PURPOSE: Glial cells are structurally and functionally linked to neuronal tissues. Pathologically, the cells may be activated and characterized by increased size and number and altered cellular properties. In glaucoma, pathologic mechanisms within the anterior optic nerve may include glial activation. This study examines morphologic changes of glial cells in the retinas of glaucomatous eyes compared with age-matched control retinas. METHODS: Paraffin-processed or flatmounted retinas from 17 human donor eyes [7 normal (donor age, 87.3 +/- 8.3 years) and 10 glaucomatous (donor age, 87.1 +/- 6.9 years)] were examined. With immunohistochemical methods, retinal glial cells were stained with an antibody to glial fibrillary acidic protein (GFAP). The morphology of the glial cells in normal and glaucomatous retinas was evaluated with fluorescence microscopy. RESULTS: Three types of glial cells were identified in flatmounted retinas with differing distributions in the peripapillary region, the nerve fiber layer (NFL), and along the capillaries. Compared with normal eyes, in glaucomatous retinas the glial cells in the peripapillary region showed an increase in density and exhibited a deformation of the end feet. The astrocytes distributed among the NFL showed little difference from normal. The astrocytes accompanying the capillary bed showed a redistribution in the glaucomatous retinas. The quantification of glial cells in paraffin-processed glaucomatous retinas exhibited a profound increase in density and a significant increase of GFAP immunoreactivity in contrast to the lightly stained glial cells in normal retinas. CONCLUSIONS: The activation of glial cells in the glaucomatous retina was characterized in changes of intensity of GFAP immunoreactivity and morphology around the larger blood vessels, compared with age-matched normal retinas. The relationships between glial cells, neuronal cells, and the vasculature, as well as the potential role of glial cells in pathologic mechanisms during different stages of neuronal damage in glaucoma, are discussed.

Aged↗
PubMed2002

[Epidemic trends of pulmonary tuberculosis and case finding in Henan province].

OBJECTIVE: Based on the data of the 4th national epidemiological survey in 2000 in Henan province, to obtain the trends of epidemic situation of pulmonary tuberculosis, and to analyze the methods of case finding. METHODS: The detection methods such as X-ray, sputum examination and PPD were used to diagnose active pulmonary tuberculosis from sampling population. RESULTS: The prevalence of active pulmonary tuberculosis is 497 per 100 000 population, the prevalence of smear positive pulmonary tuberculosis is 132 per 100 000 population. Comparing to the third survey in 1990, the reduction rate of prevalence of smear positive pulmonary tuberculosis is 6.15%, the annual reduction rate only 0.63%, indicating the prevalence declined very slowly in ten years. The rate of case finding increased by 6.6% after sputum specimens increased from 2 to 3. CONCLUSIONS: The epidemic status of pulmonary tuberculosis in Henan is still serious, and the case finding of tuberculosis should be strengthened. Increasing the times of sputum examination from 2 to 3 can increase the rate of case finding.

Adult↗
PubMed2002

[The establishment and application of antiviral screening model targeted on SAH hydrolase].

BACKGROUND: To establish a SAH hydrolase antiviral screening in vitro model for screening of broad spectrum antiviral agents. METHODS: SAH hydrolase was purified from rat livers by (NH4) 2SO4 fractionation, DEAE52,hydroxyapatite and Sephadex G-100 chromatography successively. The activity of SAH hydrolase was estimated by radio labeled substrate in synthesis direction by TLC. RESULTS: Purified SAH hydrolase showed a single band in SDS-PAGE electrophoresis with silver nitrate staining, the apparent molecular weight is 45 000. The Km for adenosine is (6.32 +- 0.17) micromol/L. The IC50 of S-DNPA, a known inhibitor of SAH hydrolase, was 7.6 micromol/L estimated in our system. The structure and activity relationships shown by racemic and regiosomer analogs of S-DHPA indicated that the structural specificity of SAH hydrolase was high. 42 compounds had been screened in the system and no compound showed more inhibitory activity against SAH hydrolase than S-DNPA. CONCLUSIONS: An in vitro antiviral screening model has been established using SAH hydrolase. It can also be used to study kinetics of enzyme inhibition.

Adenine↗
PubMed2002

[Synergetic transactivating functions of HCV core and truncated HBV middle surface protein].

OBJECTIVE: To investigate the synergetic transactivating functions of HCV core and truncated HBV middle surface proteins. METHODS: Two recombinant expression plasmids harboring HCV core and C-terminally truncated HBV middle surface protein gene were constructed, respectively. The plasmids were transfected into HepG2 cells and cotransfected HepG2 cells with reporter plasmid pSV-lacZ by lipofectamine plus reagents. The transient expressed viral proteins were identified at the transcription and translation levels. The activity of beta-galactosidase was detected, which reflected the transactivating function of the proteins. RESULTS: The protein expression of plasmids was detected in soluble cell extracts of transiently transfected HepG2 cells. HCV core protein activated the beta-galactosidase expression at a value of 4.6 times higher than the control, while C-terminally truncated HBV middle surface protein activated at a value of 3.2 times. It reached 8.4 times transfected with the plasmids simultaneously. The transactivating effect was dose dependent. CONCLUSIONS: It is suggested that the two kinds of virus proteins have transactivating effect on SV40 early promoter/enhancer, and they act synergistically. These contribute to explain the mechanisms of liver injury or tumorigenesis induced by HCV or/and HBV infection.

Hep G2 Cells↗