Biomedical subjects

Lihong Wang

Publications and source records attributed to Lihong Wang.

At least 37 records · Page 2Linked to original sources

PubMed2005

Regulation of connexin expression after balloon injury: possible mechanisms for antiproliferative effect of statins.

Statins, the 3-hydroxy-3-methylglutaryl-cooenzyme A (HMG-CoA) reductase inhibitors, have been shown to inhibit the migration of macrophages and smooth muscle cell proliferation leading to an antiproliferative effect. Although this beneficial effect of statins has been suggested to be independent of lipid lowering properties, the possible mechanisms responsible for this action is largely unknown. Gap junctions, which serve as channels for direct intercellular exchange of ions, secondary messengers, and small signaling molecules, play an important role in tissue homeostasis and regulation of growth, differentiation, and development. This study was designed to test the hypothesis that expression of the component proteins of gap junctions, connexins 40 and 43 (Cx40 and Cx43), is upregulated in arteries subjected to balloon injury and that this upregulation can be suppressed by statin therapy. Male New Zealand white rabbits were subjected to injury in which an angioplasty catheter was introduced into the right iliac artery from the femoral artery under fluoroscopic guidance. Five groups of rabbits (n = 6 to 7) were treated for 2 weeks with one of the following: balloon injury (BL); BL+lovastatin (BL+L, 10 mg/kg/day); BL+fluvastatin (BL+F, 10 mg/kg/day); sham operation (Sham); and control (Con). Immunohistochemistry studies showed that Cx40 and Cx43 were expressed in normal smooth muscle cells (SMC) throughout the media. Reverse transcription-polymerase chain reaction and Western blot analysis showed that Cx40 and Cx43 mRNA and protein expression was elevated after injury (P < .001 for both proteins and both assays), and these elevations were suppressed by lovastatin and fluvastatin to a similar degree (P < .05 for both drugs and both assays). Immunostaining of Cx40 and Cx43 was consistently enhanced in the neointimal area after injury and lovastatin and fluvastatin reduced staining of these proteins in the lessened neointimal layer. Transmission electron microscopy revealed that there were abundant gap junctions between neointimal SMC as well as fewer and smaller gap junctions after statin treatment. Therefore, balloon injury causes upregulation of Cx40 and Cx43 in neointimal SMC. Lovastatin and fluvastatin suppress upregulated Cx40 and Cx43 expression and reduce neointimal proliferation, suggesting that Cx40 and Cx43 may play a role in statin-induced antiproliferative effect.

Animals↗

PubMed2005

Abnormal expression of Rb pathway-related proteins in salivary gland acinic cell carcinoma.

Salivary gland acinic cell carcinoma (ACC) is a relatively rare neoplasm, and limited information is available regarding its molecular pathogenesis. Because the deregulation of Rb pathway is common to most human tumors, we immunohistochemically investigated the expression of Rb pathway-related proteins, including Rb, Rb proteins phosphorylated at serine 780 and 795 (pRb-S780 and pRb-S795, respectively), cyclin D1, and p16INK4a in 18 cases of ACC. The expression of topoisomerase II-alpha and Ki-67 was also examined to evaluate cell proliferation. All the ACCs exhibited substantial numbers of positive cells against Rb antibody that recognizes both unphosphorylated and phosphorylated Rb proteins. The numbers of positive cells for pRb-S795 and cyclin D1 significantly increased in ACCs as compared with normal salivary glands. Double immunofluorescent staining demonstrated that pRb-S795 was colocalized with cyclin D1 in most tumor cells. However, neither significant change of the expression of Rb protein phosphorylated at serine 780 nor its colocalization with cyclin D1 was observed. The loss of p16INK4a is infrequent, but its expression was correlated with phosphorylated Rb proteins. Our results suggest that serine 795 but not serine 780 is the preferred phosphorylation site induced by cyclin D1. This phosphorylation appeared to be critical for inactivation of Rb-mediated growth suppression and may play an important role in the pathogenesis of ACC.

Adolescent↗

PubMed2005

Amygdala activation to sad pictures during high-field (4 tesla) functional magnetic resonance imaging.

Fear-related processing in the amygdala has been well documented, but its role in signaling other emotions remains controversial. The authors recovered signal loss in the amygdala at high-field strength using an inward spiral pulse sequence and probed its response to pictures varying in their degree of portrayed sadness. These pictures were presented as intermittent task-irrelevant distractors during a concurrent visual oddball task. Relative to neutral distractors, sad distractors elicited greater activation along ventral brain regions, including the amygdala, fusiform gyrus, and inferior frontal gyrus. In contrast, oddball targets engaged dorsal sectors of frontal, parietal, and cingulate cortices. The amygdala's role in emotional evaluation thus extends to images of grief and despair as well as to those depicting violence and threat.

Adult↗

PubMed2005

[Study on chondrogenesis of rabbit bone marrow-derived mesenchymal stem cells by centrifuge-tube culture in vitro].

OBJECTIVE: To investigate the feasibility of constructing tissue engineered cartilage by inducing bone marrow-derived mesenchymal stem cells (MSCs) in centrifuge-tube culture. METHOD: By Percoll density gradient centrifuge and monolaryer culture in vitro MSCs were isolated from rabbit bone marrow and were purified. Some MSCs were seeded into centrifuge tube culture and allowed to form three-dimensional aggregates in a chemically defined medium mainly including transforming growth factor- b1 (TGF-beta1, 10 ng/ml), dexamethasone (10-7), ascorbic acid (50 microg/ml), 1% insulin, 1% selenium and 1% transferring. At day 7, 14, 21, aggregates were take out and specific markers of differentiation of cartilage were detected by the appearance of toluiding blue merachromasia and the immunohistochemistry detection of type II collagen and in situ hybridization detection of collagen type II mRNA. RESULT: MSCs seeded into centrifuge tube culture became analogous cartilage tissue after 7-21 days, their specific markers of chondrogeneses were positive in the appearance of toluiding blue merachromasia and the immunohistochemistry detection of type II collagen and in situ hybridization detection of collagen type II mRNA. CONCLUSION: MSCs have the capacity to undergo chondrogenic differentiation.

Animals↗

PubMed2005

[The effect of extracellular perfusion on dielectric spectroscopy of skeletal muscle cells].

The dielectric spectroscopy of the skeletal muscle cells is approached by extracellular perfusion, using curve fitting and numerical calculation with nonlinear Cole-Cole equation, and the dielectric parameter of skeletal muscle cells is compared after perfusion, The results show: (1) the permittivy at low frequency (epsilon1) and the conductivity at hight frequency (kappa(h)) reduces in keeping with extracellular perfusate; (2) the effect of extracellular perfusion on the characteristic frequency (f(c1),f(c2)) is small; (3) the extracellular perfusion mostly influences the peaks of deltaepsilon" and tgdelta for the skeletal muscle cells.

Animals↗

PubMed2005

[In vitro study of the directed inducing cartilage cells from rat bone mesenchymal stem cells on scaffolds].

This study was conducted to assess the cell proliferation and cell cycle of the directed inducing cartilage cells from rat bone mesenchymal stem cells on collagen sponge and compare the results with those of the plane inducing cartilage cells. The MSCs were isolated from rat bone marrow by density gradient centrifuge and adhesive property, and then were induced into chondrogenic differentiation by adding transforming growth factor-beta1 (TGF-beta1), dexamethasone, transferring and insulin on collage sponge and plane condition. Immunohistochemistry was applied to detect the expression of collagen type II on the scaffolds and plane conditions. The cell proliferation and cell cycle on different conditions were detected with MTT automated colormetric microassay and flow cytometry. The differentiation of MSCs toward chondrogenic phenotype was verified by the positive result of collagen type II on the scaffolds and plane condition. The cell viability in scaffolds was better than that in plane conditions. The S phase and G2 phase were 30 percent in whole cell cycle on the scaffold, which was different from that of the control groups. The method of using the Using directed inducing cartilage from bone MSCs combined with collage sponge to construct tissue-engineered cartilage is feasible; it is better than the method of plane directed inducing.

Animals↗

PubMed2003

Inorganic polyphosphate stimulates mammalian TOR, a kinase involved in the proliferation of mammary cancer cells.

Inorganic polyphosphate (poly P), chains of hundreds of phosphate residues linked by "high-energy" bonds as in ATP, has been conserved from prebiotic times in all cells. Poly P is essential for a wide variety of functions in bacteria, including virulence in pathogens. In this study, we observe the unique and many-fold stimulation by poly P in vitro of the protein kinase mTOR (mammalian target of rapamycin). To explore the role of poly P in mammalian cells, a yeast polyphosphatase, PPX1, was inserted into the chromosomes of MCF-7 mammary cancer cells. The transfected cells are markedly deficient in their response to mitogens, such as insulin and amino acids, as seen in their failure to activate mTOR to phosphorylate one of its substrates, PHAS-I (the initiation factor 4E-binding protein). In addition, the transfected cells are severely reduced in their growth in a serum-free medium. On the basis of these findings, we suggest that poly P (and/or PPX1) serves as a regulatory factor in the activation of mTOR in the proliferative signaling pathways of animal cells.

Base Sequence↗

PubMed2003

Expression of constitutively active Akt-3 in MCF-7 breast cancer cells reverses the estrogen and tamoxifen responsivity of these cells in vivo.

PURPOSE: Prior studies had suggested that Akt activity is elevated in a subset of breast cancers. In this study, to test the effect of active Akt-3 on estrogen receptor function, we have produced MCF-7 cells, which express active Akt-3 and examined the estrogen responsiveness of these cells in vivo and in vitro. EXPERIMENTAL DESIGN: MCF-7 cells expressing active Akt-3 were studied for estradiol (E2) responsiveness in vitro by both using an estrogen receptor element reporter construct as well as looking at induction of endogenous genes. These cells were also studied in vivo after injection into nude, ovariectomized mice by following tumor growth rates in the presence or absence of E2, tamoxifen, or the pure antiestrogen, ICI 182,780 (fulvestrant). RESULTS: Akt-3-expressing cells were found to produce tumors in mice in the absence of E2 that were approximately equivalent in size to control cells in mice given E2. Moreover, the formation of tumors by the Akt-3 cells was greatly suppressed by E2, stimulated by tamoxifen, and unaffected by ICI 182,780. In the in vitro assays for gene induction by E2, the Akt-3-expressing cells exhibited similar E2 and tamoxifen responsiveness as the control cells. CONCLUSIONS: These results indicate that expression of active Akt-3 in MCF-7 cells results in E2-independent tumor growth. Moreover, the growth of these tumors is inhibited by E2 and enhanced by tamoxifen. Finally, these tumors are resistant to ICI 182,780. These findings suggest that the amount of active Akt present in breast cancers may be important in the relative efficacy of different treatments.

Animals↗

PubMed2003

Akt promotes increased mammalian cell size by stimulating protein synthesis and inhibiting protein degradation.

Expression of constitutively active Akt3 was found to increase the size of MCF-7 cells approximately twofold both in vitro and in vivo. A regulatable version of Akt1 (MER-Akt) was also found capable of inducing a twofold increase in the size of H4IIE rat hepatoma cells. Rapamycin, a specific inhibitor of mTOR function, was found to inhibit the Akt-induced increase in cell size by 70%, presumably via inhibition of the Akt-induced increase in protein synthesis. To determine whether Akt could be inhibiting protein degradation, thereby contributing to its ability to induce an increase in cell size, we conducted protein degradation experiments in the H4IIE cell line. Activation of MER-Akt was found to inhibit protein degradation to a degree comparable to insulin treatment. The effects of these two agents on protein degradation were not additive, thereby suggesting that they were acting on a similar pathway. An inhibitor of the phosphatidylinositol 3-kinase pathway, LY-294002, blocked both insulin- and Akt-induced inhibition of protein degradation, again consistent with the hypothesis that both agents were acting on the same pathway. In contrast, rapamycin did not block the ability of either agent to inhibit protein degradation. These results indicate that Akt increases cell size through both mTOR-dependent and -independent pathways and that the latter involves inhibition of protein degradation. These studies are also consistent with the hypothesis that insulin's ability to regulate protein degradation is to a large extent mediated via Akt.

Animals↗

PubMed2003

Modulation of insulin-stimulated degradation of human insulin receptor substrate-1 by Serine 312 phosphorylation.

Ser/Thr phosphorylation of insulin receptor substrate-1 (IRS-1) is a negative regulator of insulin signaling. One potential mechanism for this is that Ser/Thr phosphorylation decreases the ability of IRS-1 to be tyrosine-phosphorylated by the insulin receptor. An additional mechanism for modulating insulin signaling is via the down-regulation of IRS-1 protein levels. Insulin-induced degradation of IRS-1 has been well documented, both in cells as well as in patients with diabetes. Ser/Thr phosphorylation of IRS-1 correlates with IRS-1 degradation, yet the details of how this occurs are still unknown. In the present study we have examined the potential role of different signaling cascades in the insulin-induced degradation of IRS-1. First, we found that inhibitors of the phosphatidylinositol 3-kinase and mammalian target of rapamycin block the degradation. Second, knockout cells lacking one of the key effectors of this cascade, the phosphoinositide-dependent kinase-1, were found to be deficient in the insulin-stimulated degradation of IRS-1. Conversely, overexpression of this enzyme potentiated insulin-stimulated IRS-1 degradation. Third, concurrent with the decrease in IRS-1 degradation, the inhibitors of the phosphatidylinositol 3-kinase and mammalian target of rapamycin also blocked the insulin-stimulated increase in Ser(312) phosphorylation. Most important, an IRS-1 mutant in which Ser(312) was changed to alanine was found to be resistant to insulin-stimulated IRS-1 degradation. Finally, an inhibitor of c-Jun N-terminal kinase, SP600125, at 10 microm did not block IRS-1 degradation and IRS-1 Ser(312) phosphorylation yet completely blocked insulin-stimulated c-Jun phosphorylation. Further, insulin-stimulated c-Jun phosphorylation was not blocked by inhibitors of the phosphatidylinositol 3-kinase and mammalian target of rapamycin, indicating that c-Jun N-terminal kinase is unlikely to be the kinase phosphorylating IRS-1 Ser(312) in response to insulin. In summary, our results indicate that the insulin-stimulated degradation of IRS-1 via the phosphatidylinositol 3-kinase pathway is in part dependent upon the Ser(312) phosphorylation of IRS-1.

Animals↗

PubMed2003

Spatiotemporal separability in the human cortical response to visual motion speed: a magnetoencephalography study.

Humans can estimate the speed of an object's motion independently of other visual information. Although speed-related neural activity is known to exist in the primate brain, there has been no physiological study that investigated where and how the speed of motion is represented in the human brain. Nine different combinations of spatial and temporal frequencies were used to make drifting sinusoidal grating of five different speeds (from 1.5 to 24 deg/s). Using the stimuli, we evaluated whether the magnetoencephalographic response property changes were due to a speed-tuned mechanism or to separable spatial and temporal frequency detection mechanisms. The latency change was caused mainly by an inseparable speed-tuned mechanism. In contrast, the amplitude was inversely related to the spatial frequency and was also affected by the temporal frequency differently depending on the frequency. Our results support the view that the human visual system has three sets of mechanisms tuned to spatial frequency, temporal frequency, and speed.

Adult↗

PubMed2003

Early sensory information processes are enhanced on visual oddball and S1-S2 tasks in Parkinson's disease: a visual event-related potentials study.

To observe sensory and cognitive information processing in Parkinson's disease (PD), 34 PD patients and 26 controls were investigated. A visual oddball paradigm and an S1-S2 paradigm were employed to record the early (P1, N1, P2) and late (N2, P3) event-related potentials (ERPs) at Cz, Pz and Oz. Results showed: (1) enlarged P1 amplitude at all electrode locations on both tasks, (2) shortened N1 latency and enlarged P2 amplitude at Oz on both tasks, (3) enlarged N1 amplitude at Cz during an oddball paradigm, (4) delayed N2 latency and decreased N2, P3 amplitude on both tasks, and (5) delayed P3 latency and reaction time during the S1-S2 paradigm. Abnormal ERP changes were correlated with worsened scores on Wechsler Adult Intelligence Scale-Revised and motor dysfunction scales in PD. We surmise overactive aspects or failed inhibitory modulation of sensory information processing in the early ERP stage and deficient cognitive information processing during the late ERP stage in PD.

Adult↗

PubMed2003

Event-related potentials during visual S1-S2 paradigm in multiple system atrophy: relation to morphologic changes on brain MRI measurement.

Although mild cognitive deficits in multiple system atrophy (MSA) have been proved on neuropsychological testing, the cognitive function in MSA has not been investigated sufficiently from an electrophysiological view point. We performed a visual Event-related potential (ERP) examination and quantitative magnetic resonance imaging (MRI) measurements on 24 MSA patients and 18 normal subjects, and investigated the relationship between the ERP abnormalities and the morphological changes of the brain in MSA patients. To elicit ERPs, we used S1-S2 task which needs frontal lobe function for execution. We found significant prolongation of P3 latency and reaction time and significant attenuation of P3 amplitude in MSA, compared with normal control values. We performed the square and linear MRI measurements on MSA and normal subjects. The cerebellum, the pons, the perisylvian cerebral area and the deep cerebral gray matter in MSA were significantly smaller than those in normal subjects. The mean value in MSA was significantly increased for the bicaudate index and Huckman number compared with those in normal subjects. In MSA, we found significant correlation between P3 latency and atrophy of the cerebellum and the pons, while we found no correlation between ERP abnormalities and quantitative MRI measurements of any other regions. Our results showed that the prolongation of visual P3 latency during S1-S2 task was significantly associated with atrophy of the cerebellum and the pons.

Aged↗

PubMed2003

[The comparative study of clinical therapy of secretory otitis media in nasopharyngeal carcinoma patients].

OBJECTIVE: To investigate the treatment of secretory otitis media in nasopharyngeal carcinoma (NPC) patients. METHOD: Fifty eight patients of NPC with secretory otitis media were divided into two group by random before radiotherapy. Patients were treated by nasal and nasopharyngeal debridement and cleansing and tympanic membrane puncturing suction in group I, while patients were treated by myringotomy or ventilation tube insertion in Group II. After the patients were followed up for six months, the two group were compared by efficient rate and complication rate. RESULTS: Fifty one out of total 58 patients survived after half an years follow-up. Statistics of surviving patients showed the efficient rate in group I was 82.1% versus 57.1% in group II. Differentiation was found between two group (chi 2 = 4.14, P < 0.05). Complication rate was 3.6% in group I and 28.6% in group II. There was differentiation between two group (chi 2 = 4.7, P < 0.05). CONCLUSION: The nasal and nasopharyngeal debridement and cleaning and eardrum puncturing suction was superior to myringotomy or ventilation tube insertion.

Adult↗

PubMed2002

Electromagnetic re-warming of cryopreserved tissues: effect of choice of cryoprotectant and sample shape on uniformity of heating.

A method that has been proposed for the cryopreservation of tissues and organs is to add a cryoprotective agent (CPA) in sufficient concentration to allow vitrification, and to use rapid electromagnetic heating to prevent the formation of ice crystals during the re-warming. We have compared the physical and biological properties of four CPAs, measuring the speed and uniformity of heating in a 36 mm sphere placed in a 434 MHz applicator, and the toxicity to ECV304 endothelial cells. Ethanediol and dimethyl sulfoxide were found to be suitable for rapid, uniform heating but toxic to the endothelial cells at vitrifying concentrations. Butane-2,3-diol was less toxic, but the heating patterns were unacceptably non-uniform. Propane-1,2-diol was not significantly more toxic than butane-2,3-diol, and did allow uniform heating. It is therefore the best choice of CPA for the vitrification of tissues. We have shown that the uniformity of heating correlates with the dielectric properties of the perfusate. Furthermore, we have shown that uniform heating is feasible in non-spherical samples provided they are approximately ellipsoidal.

Butylene Glycols↗

PubMed2002

Visual event-related potential changes in two subtypes of multiple system atrophy, MSA-C and MSA-P.

We investigated the visual event-related potentials (ERPs) in two subtypes of multisystem atrophy (MSA) in 15 MSA-C patients, 12 MSA-P patients, and 21 normal control (NC) subjects. We used a visual oddball task to elicit ERPs. No significant changes were seen in N1 or N2 latency, in either MSA-C or MSA-P, compared with the NC group. An early stage of visual information process related to N1 and a visual discrimination process related to N2 might be preserved in both MSA-C and MSA-P. The P3a peak was more frequently undetectable in MSA than in the NC group. Significant P3a amplitude reduction in both MSA-C and MSA-P suggests impairment of the automatic cognitive processing in both MSA-C and MSA-P. Significant difference was found in P3b latency and P3b amplitude only in MSA-C, compared with the NC group. The result suggests the impairment of the controlled cognitive processing after the visual discrimination process in the MSA-C group. We further investigated the correlation between visual ERP changes and magnetic resonance imaging (MRI) data. Quantitative MRI measurements showed reduced size of the pons, cerebellum, perisylvian cerebral area, and deep cerebral gray matter in both MSA-C and MSA-P, and of the corpus callosum only in MSA-P, as compared to NC group. In both MSA-C and MSA-P, P3b latency was significantly correlated with the size on MRI of the pons and the cerebellum. P3b latency in the whole MSA group was also significantly correlated with the size of the pons and the cerebellum. These results indicate that P3b latency changes in parallel with the volume of the pons and the cerebellum in both MSA-C and MSA-P.

Adult↗

PubMed2002

[The relationship of p53 gene mutation to cell differentiation and metastasis of laryngeal squamous cell carcinoma].

OBJECTIVE: To inquire about the relationship of p53 gene mutation to the histopathological findings and clinical manifestation in cases of laryngeal squamous cell carcinoma(LSCC). METHODS: The fresh samples from 60 cases of LSCC were examined. Polymerase chain reaction and silver staining-single strand conformation polymorphism (PCR-SSCP) and DNA direct sequencing were used to detect the mutation of p53 gene in exons 5-8. RESULTS: The mutation rates were 69.2% and 85.3% in patients at clinical stage I-II and stage III-IV respectively (P>0.05). In the well-, moderately- and poorly-differentiated cell of LSCC, the mutation rates were 52.9%, 83.3% and 94.7% respectively (P<0.05). The p53 gene mutation rate of LSCC patients with neck lymph-node metastasis was 96.4%, whereas that of patients without neck lymph-node metastasis was 62.5% (P<0.05). Twenty samples showed positive results in SSCP; 19 samples showed deletion and mutation in codons 125-292 by DNA direct sequencing. CONCLUSION: The mutation of p53 gene in exons 5-8 was closely related to cell differentiation and the neck lymph-node metastasis of LSCC, but it was not related to the clinical stages of the LSCC cases.

Carcinoma, Squamous Cell↗

PubMed2002

Complications and conversions in myeloproliferative disorders: an analysis of 356 cases.

OBJECTIVE: To investigate the complications and conversions in myeloproliferative disorders (MPD). METHODS: Three hundred and fifty six patients with MPD were reviewed, including 78 with etiologic thrombocythemia (ET), 93 with primary myelofibrosis (MF), 185 with polythythemia vera (PV). The clinical observation, follow-up, analysis with SPSS statistic software were performed. RESULTS: Out of the 356 cases, 101 (28.5%) developed thromboembolic events, 81 (22.8%) hemorrhage, 60 (16.9%) hypertension, 20 (5.6%) coronary heart disease, 3 (0.8%) hemolysis and 1 (0.3%) gastrointestinal ulcer, 2 (0.6%) calculus and 1 (0.3%) bone marrow necrosis. Twenty four patients (6.7%) developed MF (9 in ET, 15 in PV), 2 (0.6%) erythrocytosis (1 in ET, 1 in MF), 3 (0.8%) thrombocythemia (all in PV), 5 (1.4%) acute leukemia (2 in ET, 3 in MF) and 1 (0.3%) multiple myeloma (in ET). Eleven cases (3.1%) died, 5 (1.4%) from acute leukemia, 2 (0.6%) fatal hemorrhages, 1 (0.3%) each myocardial infarction and infectious shock, 2 (0.6%) unknown causes. CONCLUSION: Embolism and bleeding were the main complications in MPD. Conversions among ET, MF and PV hematological malignancies could occur.

Adolescent↗