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Biomedical subjects

Lei Wang

Publications and source records attributed to Lei Wang.

At least 235 records · Page 13Linked to original sources

[Hand-assisted video-thoracoscopy for resection of esophageal cancer].

OBJECTIVE: To explore the feasibility and advantages of hand-assisted video-thoracoscopy for resection of esophageal cancer. METHODS: Forty-five patients with esophageal cancer received hand-assisted video-thoracoscopic esophagectomy (group I). 45 patients underwent esophagectomy through routine open thoracotomy during the same period as control (group II). The data of lymph node resection, operating time and blood loss were compared. RESULTS: There were no operative mortality in 2 groups. In group I, the number of dissected paraesophageal lymph nodes, cardiac lymph nodes and left gastric nodes were (3.6 +/- 1.0), (1.3 +/- 1.1) and (4.3 +/- 1.4), respectively. While for group II the dissected lymph nodes were (3.3 +/- 1.5), (1.6 +/- 1.1) and (4.7 +/- 2.1), respectively. There was no significant difference between two groups (P > 0.05). However, the number of dissected mediastinal nodes was (6.6 +/- 3.7) for group I and (3.8 +/- 2.5) for group II (chi(2) = 2.95, P < 0.05). The mean operating time was (29 +/- 5) minutes for group I and (60 +/- 6) minutes for group II. The mean blood loss was (93 +/- 19) ml for group I and (145 +/- 35) ml for group II. The mean chest tube drainage was (201 +/- 45) ml for group I and (295 +/- 57) ml for group II in the first postoperative day. The difference in above parameters between 2 groups was significant (chi(2) = 18.69, 6.13, 6.08, P < 0.001). CONCLUSIONS: It is suggested that hand-assisted video-thoracoscopic esophagectomy is a safer, minimal invasive procedure in the resection of esophagus carcinoma.

Adult↗

[Photodynamic diagnosis and fluorescence-guided resection of malignant gliomas: a report of 15 cases].

OBJECTIVE: To study the usefulness of the intraoperative photodynamic diagnosis (PDD) and fluorescence-guided resection of malignant gliomas. METHODS: Fifteen consecutive patients with malignant gliomas received doses of hematoporphyrin derivative (HPD, 2 mg/kg body weight) 48 hours before induction of anesthesia. After the tumors recognized by bare eyes they were removed routinely. The fluorescence around 690 nm excited by laser beam (wavelength 632.5 nm) was detected by laser electronic spectrum analyzer and then fluorescing tissue was removed whenever it was considered safel. Tissue samples derived from the walls of tumor cavities after resection and PDD were sent for histological examination. Compared with the result of the histological examination, the sensitivity and specificity of PDD were calculated and recorded. Early postoperative MRI or CT were done to determine the extend of the resection of the tumors. Surgical mortality and morbidity were also recorded. RESULTS: Intraoperatively, in all of 15 cases tumor areas with HPD fluorescence could be recognized by laser electronic spectrum analyzer. On the basis of 106 tissue samples derived from 15 tumors, a sensitivity of 90.6%, a specificity of 96.8% and an accuracy of 94.3% of PDD were achieved. In 2 cases the resection of residual tumor were performed after finding left tumors by PDD. Complete resection of contrast-enhancing tumor was accomplished in 9 patients (60%). Residual intraoperative tissue fluorescence left unresected for safety reasons predicted residual enhancement on MR images in 5 of the 6 remaining patients. No perioperative deaths and one case of morbidity were encountered. CONCLUSIONS: Intraoperative photodynamic diagnosis following resection of malignant gliomas can detect residual tumor tissue with high accuracy. Photodynamic diagnosis and fluorescence-guided resection of malignant gliomas have a positive role in improving the radicality of malignant glioma resection.

Adult↗

Light-induced mutagenicity in Salmonella TA102 and genotoxicity/cytotoxicity in human T-cells by 3,3'-dichlorobenzidine: a chemical used in the manufacture of dyes and pigments and in tattoo inks.

DCB, 3,3'-dichlorobenzidine, is used primarily as an intermediate in the manufacture of diarylide yellow or azo red pigments for printing ink, textile, paint, and plastics. It is also used in tattoo inks. In this article, we investigate light-induced toxicity of DCB in both bacteria and human Jurkat T-cells. DCB itself is not toxic or mutagenic to Salmonella typhimurium TA102, but is photomutagenic at concentrations as low as 2 microM and phototoxic at concentrations >100 microM when bacteria are exposed to DCB and light at the same time (1.2 J/cm2 of UVA and 2.1 J/cm2 of visible light). Furthermore, DCB is both photocytotoxic and photogenotoxic to human Jurkat T-cells. Under a light irradiation dose of 2.3 J/cm2 of UVA and 4.2 J/cm2 of visible light, it causes the Jurkat T-cells to become nonviable in a DCB dose-dependent manner and the nonviable cells reaches 60% at DCB concentrations higher than 50 microM. At the same time, DNA fragmentation is observed for cells exposed to both DCB and light, determined by single cell gel electrophoresis (alkaline comet assay). As much as 5% (average) DNA fragmentation was observed when exposed to 200 microM DCB and light irradiation. This suggests that DCB can penetrate the cell membrane and enter the cell. Upon light activation, DCB in the cells can cause various cellular damages, leading to nonviable Jurkat T-cells. It appears, the nonviable cells are not caused solely by fragmentation of cellular DNA, but by other damages such as to proteins and cell membranes, or DNA alkylation. Therefore, persons exposed to DCB through environmental contamination or through tattoo piercing using DCB-containing inks must not only concern about its toxicity without exposing to light, but also its phototoxicity.

3,3'-Dichlorobenzidine↗

Identification of white spot syndrome virus (WSSV) envelope proteins involved in shrimp infection.

White spot syndrome virus (WSSV) is a major shrimp pathogen causing large economic losses. In an attempt to identify the envelope proteins involved in virus infection, antisera against six WSSV envelope proteins were used in neutralization assays conducted in vivo. The results showed that the virus infection could be significantly delayed or neutralized by antibodies against three WSSV envelope proteins (VP68, VP281 and VP466). This neutralization was further confirmed by quantitative PCR. It could be concluded that the viral envelope proteins VP68, VP281 and VP466 played roles in WSSV infection to shrimp.

Animals↗

A role of STAT3 in Rho GTPase-regulated cell migration and proliferation.

Rho family GTPases and STAT3 act as mediators of cytokine and growth factor signaling in a variety of cellular functions involved in inflammation, tumorigenesis, and development. In the course of searching for their functional connections, we found by using STAT3 knock-out mouse embryonic fibroblasts that RhoA, Rac1, and Cdc42 could cause nonspecific activation of STAT3 promoter-driven luciferase reporter in the absence of STAT3, raising concerns to a body of literature where STAT3 was associated with Rho GTPases based on the reporter system. We also found that although active RhoA, Rac1, and Cdc42 could all mediate Ser-727 and Tyr-705 phosphorylation and nuclear translocation of STAT3, the Rho GTPases were able to induce STAT3 activation independently of the interleukin-6 autocrine pathway, and active RhoA, Rac1, or Cdc42 could not form a stable complex with STAT3 as previously suggested, indicating an unappreciated mechanism of STAT3 activation by the Rho GTPases. The RhoA-induced STAT3 activation partly depended on Rho-associated kinase (ROK) and involved multiple effector signals as revealed by the examination of effector domain mutants of RhoA. Genetic deletion of STAT3 led to a loss of response to RhoA in myosin light chain phosphorylation and actin stress fiber induction but sensitized the cells to RhoA or ROK-stimulated cell migration. STAT3 was required for the RhoA-induced NF-kappaB and cyclin D1 transcription and was involved in NF-kappaB nuclear translocation. Furthermore, loss of STAT3 expression inhibited RhoA-promoted cell proliferation and blocked RhoA or ROK induced anchorage-independent growth. These phenotypic changes in STAT3-/- cells could be rescued by reconstituting STAT3 gene. Our studies carried out in STAT3 null cells demonstrate unambiguously that STAT3 represents an essential effector pathway of Rho GTPases in regulating multiple cellular functions including actin cytoskeleton reorganization, cell migration, gene activation, and proliferation.

Actins↗

Regulation of hepcidin transcription by interleukin-1 and interleukin-6.

Hepcidin is a peptide that regulates iron homeostasis by inhibiting iron absorption by the small intestine and release of iron from macrophages. Its production is stimulated by iron overload and by inflammation. It has been suggested that IL-6 is the only cytokine that stimulates hepcidin transcription. However, mice with targeted disruption of the gene encoding IL-6 (IL-6-/-) respond to endotoxin by increasing the expression of hepcidin transcripts in the liver. We show that incubating murine hepatocytes with IL-6, IL-1alpha, and IL-1beta strongly stimulates hepcidin transcription. IL-10 has little or no stimulatory effect, and IFN-beta inhibits transcription of hepcidin. All of the hepcidin stimulatory activity of macrophages from IL-6-/- mice can be accounted for by IL-1 that they secrete. Hepatocytes from IL-6-/- mice, hfe-/- mice, and mice with a hypomorphic transferrin receptor 2 mutation responded to IL-6 and IL-1 by up-regulating hepcidin transcription. Nitric oxide does not seem to be involved in the stimulation of hepcidin transcription by cytokines: aminoguanidine does not inhibit the stimulation of hepcidin transcription by cytokines. IL-1 may play a significant role in the anemia of inflammation by up-regulating hepcidin.

Animals↗

Chemopreventive effect of five drugs on renal interstitial fibrosis induced by an aristolochic acid-containing Chinese herb in rats.

BACKGROUND/AIMS: This study focuses on the chemopreventive effect of five drugs on renal interstitial fibrosis induced by an aristolochic acid-containing Chinese herb Mu-Tong. METHODS: Renal interstitial fibrosis was induced in rats by administration of the Mu-Tong solution intragastrically for 6 weeks, and 36 rats were randomly divided into six groups: (1) Mu-Tong, (2) Mu-Tong + captopril, (3) Mu-Tong + losartan, (4) Mu-Tong + simvastatin, (5) Mu-Tong + spironolactone, and (6) Mu-Tong + diammonium glycyrrhizinate. Blood biochemistry and extracellular matrix were detected at weeks 0, 2, 4, and 6. At the end of week 6, kidney tissue of all groups was evaluated with special Masson staining for the degree of renal fibrosis as well as regular histopathology. RESULTS: Mu-Tong caused progressive elevation of blood urea nitrogen, creatinine, hyaluronic acid, procollagen type III, and laminin. All five drugs suppressed elevation of blood biochemistry and extracellular matrix to some degree, but only the simvastatin group showed a significantly reduced percentage of positive Masson staining area in renal section compared to the Mu-Tong group (p < 0.05). CONCLUSIONS: Our study indicates that Mu-Tong induces a similar kidney injury with general characteristics in patients with renal interstitial fibrosis. All five different drugs have suppressive effects on Mu-Tong-induced renal function damage, and in particular, simvastatin shows a protective effect on development of Mu-Tong-induced renal interstitial fibrosis to a certain degree.

Animals↗

Accuracy of structure-derived properties in simple comparative models of protein structures.

The accuracy of comparative models of proteins is addressed here. A set of 12,732 single-template models of sequences of known high-resolution structures was built by an automated procedure. Accuracy of several structure-derived properties, such as surface area, residue accessibility, presence of pockets, electrostatic potential and others, was determined as a function of template:target sequence identity by comparing models with their corresponding experimental structures. As expected, the average accuracy of structure-derived properties always increases with higher template:target sequence identity, but the exact shape of this relationship can differ from one property to another. A comparison of structure-derived properties measured from NMR and X-ray structures of the same protein shows that for most properties, the NMR/X-ray difference is of the same order as the error in models based on approximately 40% template:target sequence identity. The exact sequence identity at which properties reach that accuracy varies between 25 and 50%, depending on the property being analyzed. A general characteristic of simple comparative models is that their surface has increased area as a consequence of being more rugged than that of experimental structures. This suggests that including solvent effects during model building or refinement could significantly improve the accuracy of surface properties in comparative models.

Amino Acids↗

Direct and indirect effects of fetal irradiation on cortical gray and white matter volume in the macaque.

BACKGROUND: Schizophrenia is associated with reductions in thalamic neuronal number and cortical gray matter volume. Exposure of nonhuman primates to x-irradiation in early gestation has previously been shown to decrease thalamic volume and neuronal number. Here we examine whether early gestational irradiation also results in cortical volume reduction. METHODS: High-resolution, T1-weighted magnetic resonance scans were collected in adult monkeys 1) exposed to irradiation during the early gestational period (E33-E42) corresponding to thalamic neurogenesis, 2) irradiated in midgestation (E70-81) during neocortical neurogenesis, and 3) not exposed to irradiation. Cortical gray matter and white matter volumes were derived via manual segmentation; frontal and nonfrontal volumes were distinguished via sulcal landmarks. RESULTS: Monkeys irradiated in early gestation exhibited a trend reduction in nonfrontal gray matter volume (17%) and significant reductions in white matter volume in frontal (26%) and nonfrontal (36%) lobes. Monkeys irradiated in midgestation had smaller gray (frontal: 28%; nonfrontal: 22%) and white matter (frontal: 29%; nonfrontal: 38%) volumes. CONCLUSIONS: The cortical deficits observed in midgestationally irradiated monkeys are consistent with a reduction in cortical neuronal number. Cortical volume reductions following early gestational irradiation may be secondary to reduced thalamic neuronal number and therefore model the thalamocortical pathology of schizophrenia.

Age Factors↗

Neuroanatomical predictors of response to donepezil therapy in patients with dementia.

BACKGROUND: Patients with dementia of the Alzheimer type (DAT) respond variably to treatment with acetylcholinesterase inhibitors. OBJECTIVE: To determine whether measures of hippocampal volume and shape predict the response to donepezil in patients with DAT. DESIGN: T1-weighted, magnetic resonance images were obtained from patients with DAT, who subsequently underwent treatment with donepezil. Brain-mapping algorithms were used to quantify hippocampal volume and shape, and growth curves were used to estimate clinical outcome. SETTING: A referral outpatient center specializing in treatment of dementia. PATIENTS: Thirty-seven patients with very mild or mild DAT received donepezil therapy for up to 4 weeks before magnetic resonance imaging and for 24 to 96 weeks after magnetic resonance imaging. INTERVENTION: Donepezil, 10 mg/d. MAIN OUTCOME MEASURE: Rate of change in the cognitive portion of the Alzheimer's Disease Assessment Scale total scores. RESULTS: Smaller hippocampal volume and inward variation of the lateral and inferomedial portions of the hippocampal surface were correlated with a poorer response to donepezil therapy. CONCLUSIONS: Measures of hippocampal volume and surface variation can be used to predict the response of patients with DAT to the acetylcholinesterase inhibitor donepezil.

Alzheimer Disease↗

Gliosis and brain remodeling after treatment of stroke in rats with marrow stromal cells.

The long-term (4-month) responses to treatment of stroke in the older adult rat, using rat bone marrow stromal cells (MSCs), have not been investigated. Retired breeder rats were subjected to middle cerebral artery occlusion (MCAo) alone, or injected intravenously with 3 x 10(6) MSCs, at 7 days after MCAo. Functional recovery was measured using an adhesive-removal patch test and a modified neurological severity score. Bromodeoxyuridine, a cell proliferation marker, was injected daily for 14 before sacrifice. Animals were sacrificed 4 months after stroke. Double immunostaining was used to identify cell proliferation and cell types for axons, astrocytes, microglia, and oligodendrocytes. MSC treatment induced significant improvement in neurological outcome after MCAo compared with control rats. MSC treatment reduced the thickness of the scar wall (P < 0.05) and reduced the numbers of microglia/macrophages within the scar wall (P < 0.01). Double staining showed increased expression of an axonal marker (GAP-43), among reactive astrocytes in the scar boundary zone and in the subventricular zone in the treated rats. Bromodeoxyuridine in cells preferentially colocalized with markers of astrocytes (GFAP) and oligodendrocytes (RIP) in the ipsilateral hemisphere, and gliogenesis was enhanced in the subventricular zone of the rats treated with MSCs. This is the first report to show that MSCs injected at 7 days after stroke improve long-term neurological outcome in older animals. Brain tissue repair is an ongoing process with reactive gliosis, which persists for at least 4 months after stroke. Reactive astrocytes responding to MSC treatment of ischemia may also promote axonal regeneration during long-term recovery.

Animals↗

p53 protein activates the transcription of human proliferating cell nuclear antigen in response to 4-nitroquinoline N-oxide treatment.

4-nitroquinoline N-oxide (4-NQO) is a potent mutagen and carcinogen. To elucidate the cellular response to 4-NQO, we studied the transcriptional regulation of human proliferating cell nuclear antigen (hPCNA), an essential protein in DNA replication and repair, after 4-NQO treatment. We found that hPCNA promoter was dose-dependently transactivated by 4-NQO under the concentration of 2 microM via a previously reported p53-binding element located from -236 to -217 upstream of the transcription start site. Based on our western blot analysis, the phosphorylation of serine at the 15th residue (Ser15) of p53 was activated by 4-NQO, whereas the level of p53 in the cells did not change much. It was observed that Staurosporine, a Ser/Thr kinase inhibitor, blocked the Ser15 phosphorylation of p53 and the hPCNA promoter response to 4-NQO simultaneously, suggesting that Ser15 phosphorylated p53 was the 4-NQO-responsive hPCNA regulator. The [3H]-thymidine deoxyribose (TdR) incorporation assay and the comet assay showed that DNA repair was triggered when DNA replication was inhibited after the treatment of 4-NQO, and the hPCNA transactivation seemed to contribute to DNA repair. Taken together, our data indicate that after 4-NQO treatment hPCNA is transactivated by Ser15 phosphorylated p53, and participate in DNA repair.

4-Nitroquinoline-1-oxide↗

Amphioxus allantoicase: molecular cloning, expression and enzymatic activity.

Allantoicase, one of the purine metabolism enzymes, is progressively truncated during the chordate evolution, yet it is unknown when its activity became phylogenetically extinct. In this study, a cDNA encoding allantoicase was isolated from the gut cDNA library of amphioxus Branchiostoma belcheri tsingtauense. It is 2441 bp long, and contains an open reading frame encoding a protein of 392 amino acid residues. RT-PCR analysis showed that amphioxus allantoicase was strongly expressed in the hepatic caecum, and weakly expressed in other tissues including hind-gut, gill, muscle, notochord, testis and ovary. The parallel experiment was performed measuring the allantoicase activity in the same tissues revealed that its activity was high in the hepatic caecum, but low or undetectable in other tissues examined. These suggest that allantoicase remains in action in the primitive chordate amphioxus.

Animals↗

Cytokine signals through STAT3 promote expression of granulocyte secondary granule proteins in 32D cells.

OBJECTIVE: In a previous study, we showed that activation of a transfected human erythropoietin receptor (EPOR) in the murine myeloid cell line 32D resulted in the development of morphologic features of granulocytic differentiation and expression of the neutrophil primary granule protein myeloperoxidase. We now studied if EPOR signaling could also mediate secondary granule protein gene expression and investigated the signal transduction requirements for induction of secondary granule gene expression in 32D cells. MATERIALS AND METHODS: Wild-type and variant 32D cells expressing normal or chimeric EPORs or receptors for granulocyte colony-stimulating factor (G-CSFRs) were stimulated with EPO or G-CSF and the expression of granulocyte-specific genes was analyzed by Northern blot analysis. To determine the signaling mechanisms required for secondary granule protein gene induction, the activation of STAT pathways following growth factor stimulation was studied by Western blot analysis. RESULTS: We found that EPO treatment of 32D cells engineered to express EPOR did not result in induction of the secondary granule protein genes encoding lactoferrin and 24p3 lipocalin, the mouse homolog of human N-Gal, or the myeloid transcription factor C/EBPepsilon. Replacement of the intracellular domain of EPOR with the intracellular domain of G-CSFR in a chimeric receptor was associated with EPO-mediated induction of lactoferrin, 24p3 lipocalin, and C/EBPepsilon genes. We found that STAT3 phosphorylation was mediated by the intracellular domain of G-CSFR, but not EPOR. Replacement of one or two of the STAT5 binding sites in the intracytoplasmic domain of the EPOR with STAT3 binding sites resulted in EPO-mediated STAT3 activation and a marked increase in the expression of the 24p3 lipocalin gene. Knockdown of STAT3 protein levels with siRNA caused significant decrease in 24p3 lipocalin gene induction. CONCLUSION: These results indicate that EPOR signaling cannot substitute for G-CSFR signaling to stimulate secondary granule protein gene expression in 32D cells. In addition, STAT3 is a critical mediator of 24p3 lipocalin gene expression in these cells.

Animals↗

Activation of the PI3-K/Akt pathway mediates cGMP enhanced-neurogenesis in the adult progenitor cells derived from the subventricular zone.

The intracellular mechanisms that regulate neurogenesis remain unclear. Using neurospheres isolated from the subventricular zone (SVZ) of the adult rat, we investigated the effect of cyclic guanosine monophosphate (cGMP) and its signaling pathway on the induction of neurogenesis. Neurospheres expressed phosphodiesterase 5 (PDE5) and treatment of neurospheres with Sildenafil, a specific inhibitor of PDE5, significantly increased cGMP levels and neurogenesis. In addition, incubation of neurospheres with Sildenafil significantly phosphorylated Akt, which was associated with an increase of phosphorylation of glycogen synthase kinase 3 (GSK-3), a downstream target of Akt. Coincubation of neurospheres with Sildenafil and LY 294002, a pharmacological inhibitor of PI3-K/Akt, abolished Sildenafil-induced phosphorylated Akt and GSK-3. Furthermore, LY 294002 blocked Sildenafil-increased SVZ cell proliferation. These data suggest that Sildenafil-enhanced neurogenesis likely occurs through activation of the PI3-K/Akt/GSK-3 pathway.

3',5'-Cyclic-GMP Phosphodiesterases↗

Anomalous heat conduction and anomalous diffusion in nonlinear lattices, single walled nanotubes, and billiard gas channels.

We study anomalous heat conduction and anomalous diffusion in low-dimensional systems ranging from nonlinear lattices, single walled carbon nanotubes, to billiard gas channels. We find that in all discussed systems, the anomalous heat conductivity can be connected with the anomalous diffusion, namely, if energy diffusion is sigma(2)(t)=2Dt(alpha) (0 1) implies an anomalous heat conduction with a divergent thermal conductivity (beta>0), and more interestingly, a subdiffusion (alpha<1) implies an anomalous heat conduction with a convergent thermal conductivity (beta<0), consequently, the system is a thermal insulator in the thermodynamic limit. Existing numerical data support our theoretical prediction.

Carbon↗

Characterization and expression profile of AmphiCD63 encoding a novel member of TM4SF proteins from amphioxus Branchiostoma belcheri tsingtauense.

The study on CD antigen genes remains lacking in the cephalochordate amphioxus to date. In this report, the cDNA encoding CD63 was identified for the first time from the gut cDNA library of amphioxus Branchiostoma belcheri tsingtauense. Primary structural examination showed that the protein encoded by the cDNA contained four potential transmembrane domains characteristic of transmembrane 4 superfamily (TM4SF) proteins and a conserved CCG motif in the putative major extracellular loop. BLAST search revealed that the cDNA is closely associated with other known CD63 antigen genes, and it was thus designated AmphiCD63. Phylogenetic analysis indicated that AmphiCD63 is extremely close to vertebrate CD63, CD151 and CD53, suggesting they may have been evolved from a common ancestral gene. RT-PCR analysis exhibited that AmphiCD63 mRNA was abundant in muscle, ovary, foregut including hepatic caecum and hindgut, while it was present at considerably lower levels in notochord and gill and absent in testis.

Amino Acid Sequence↗