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Biomedical subjects

Wei Han

Publications and source records attributed to Wei Han.

At least 55 records · Page 3Linked to original sources
PubMed2006

[IL-10 gene modification on immature dendritic cells induces antigen-specific tolerance in experimental autoimmune myocarditis].

OBJECTIVE: To investigate whether IL-10 gene modification on immature dendritic cells (iDC) could induce autoimmune tolerance in rat experimental autoimmune myocarditis (EAM). METHODS: EAM was induced by cardiac myosin immunization on day 0 and day 7 in rats. A total of 2 x 10(6) mature DC (mDC), iDC, pcDNA3 transfected iDC, pcDNA3-IL-10 transfected iDC or PBS were injected intravenously at 5th immunization day. Three weeks later, echocardiography and HE staining were performed to observe the cardiac function and myocardial inflammation. Th1/Th2 cytokines were detected by ELISA and MHC-II molecules, costimulatory molecules were identified by flow cytometry. In vitro T lymphocyte proliferation assay and adoptive transfer of DCs were performed to determine the antigen specific tolerance induced by IL-10 gene modification on iDCs. RESULTS: EAM rats treated with pcDNA3-IL-10 transfected iDC showed improved cardiac function and reduced inflammatory cells infiltration into myocardium. Moreover, lower Th1 and higher Th2-type response was induced, MHC-II and costimulatory molecules down-regulated and antigen specific immunological responses towards cardiac myosin inhibited in pcDNA3-IL-10-iDC treated EAM rats. CONCLUSION: Treatment with IL-10 gene modified iDCs could ameliorates EAM by inducing Th2 polarization and down-regulation of MHC-II molecules and costimulatory molecule expressions.

Animals↗
PubMed2006

[Establishing the linkage disequilibrium pattern for the all-trans-retinol dehydrogenase (RDH8) gene].

OBJECTIVE: As part of an on-going effort to map genes involved in complex eye diseases, myopia in particular, single nucleotide polymorphisms (SNPs) and linkage disequilibrium (LD) pattern were used to identified the gene within and around the All-trans-retinol dehydrogenase (RDH8). METHODS: Denaturing high-performance liquid chromatography (DHPLC) was used to screen SNPs in 4 DNA pools each consisting of DNA from five individuals, and genotypes identified SNPs coupled with DNA pooling strategy were performed in 150 Chinese subjects from Hong Kong. The identified common SNPs were included in LD and haplotype analysis using the Haploview2.05 and EH programs. RESULTS: Fifteen SNPs were identified: 7 were common with the minor allele frequency > 0.05, and 10 were novel. Four SNPs in the 3' region exhibited significant LD (/|D'/ > 0.75 and its confidence interval suggesting strong LD, r2 > 0.33, P < 0.031) and formed a haplotype block while 3 common SNPs in the 5' region did not exhibit obvious LD. CONCLUSION: The block-like LD pattern existed around the RDH8 gene region suggest that one SNP (RDH8E5a probably) in the 3' region and at least 2 SNPs in the 5' region (RDH851 particularly) were needed in association studies involving RDH8.

Alcohol Oxidoreductases↗
PubMed2006

[Clinicopathologic study of ischemic intestinal disease due to mesenteric venous lesions].

OBJECTIVE: To study the clinical and pathologic features of ischemic intestinal disease due to mesenteric phlebitis. METHOD: The clinical and pathologic features of the mesenteric venous lesions in 3 patients of ischemic intestinal disease admitted during the period from 2003 to 2004 were studied. RESULTS: All 3 patients had a clinical history of acute abdominal pain accompanying with a diffuse peritonitis. During operation, an infarcted intestinal segment was identified and was resected respectively in each patient. Histologic examination showed a lymphocytic infiltration and fibrinoid necrosis of the small to medium-sized veins, associated with mural thrombosis and infarction of the corresponding intestinal wall and mesentery. The mesenteric arteries were spared. Two-year follow up of one case showed no evidence of local recurrence or systemic vasculitis. CONCLUSIONS: Ischemic intestinal disease due to mesenteric phlebitis is a rare entity with a pathological feature of inflammation of venous wall accompanying with the development of mural thrombosis and subsequent haemorrhagic infarction of intestine. The etiology is unknown and surgical resection of the involved intestinal segment is usually recommended.

Adult↗
PubMed2006

[Allogenic stem cell transplantation from genotypically HLA-identical siblings for 30 patients with myelodysplastic syndromes].

OBJECTIVE: To explore the indication and optimum time for treating myelodysplastic syndrome (MDS) by allogeneic hematopoietic stem cell transplantation (allo-HSCT) with HLA identical sibling grafts. METHODS: From June 1997 to Sep. 2004, a total of 30 patients with MDS were treated with allo-HSCT from HLA-identical sibling donors in our institute. On HSCT, 4 patients had refractory anemia (RA) , 2 RA with ringed sideroblasts (RARS) , 7 RA with excess blasts(RAEB) , 14 RAEB in transformation (RAEB-t) , 3 already progressed to secondary AML. For IPSS system, 6 patients were in intermediate- I risk group, 11 in intermediate- li risk group, and 13 in high risk group. The modified BU/CY conditioning regimen was used. Four patients received bone marrow transplantation (BMT), 8 received peripheral blood stem cell transplantation (PBSCT) , and 18 received BMT + PBSCT. RESULTS: The 3-year expected overall survival (OS) was 63.61%, 3-year expected disease-free survival ( DFS) 61.41%, and relapse rate 5.26%; OS for RA/ RAS, RAEB and RAEB-t/AML subgroup was 83.33%, 34.29% and 66.67% , respectively, and all had no statistic difference among them. OS for IPSS-intermediate and high risk subgroup was 64.7% , and 69.0% respectively, also had no statistic difference. 3-year expected OS in no aGVHD,grade I - II aGVHD and grade III - IV aGVHD group was 57.75% , 100% and 0% , respectively (P = 0.009). Pre-HSCT chemotherapy, disease subtype and cGVHD all had no correlation with LFS or OS (P > 0.05). CONCLUSION: For young MDS patients having HLA-identical sibling donors, HSCT should be the first line therapy and performed as soon as possible.

Adolescent↗
PubMed2005

Conditioning including antithymocyte globulin followed by unmanipulated HLA-mismatched/haploidentical blood and marrow transplantation can achieve comparable outcomes with HLA-identical sibling transplantation.

The outcomes of 293 patients with leukemia undergoing HLA-identical sibling (n = 158) or related HLA-mismatched (n = 135) hematopoietic cell transplantation (HCT) performed during the same time period were compared. Patients received BUCY2 in HLA-identical sibling HCT or BUCY2 + ATG in mismatched HCT as conditioning regimens, followed by unmanipulated marrow and/or peripheral blood (PB) transplantation. All patients achieved full engraftment. The cumulative incidences of grades II to IV acute graft-versus-host disease (aGVHD) in the matched and mismatched cohorts were 32% (CI, 25%-39%) versus 40% (CI, 32%-48%, P = .13), respectively, with the relative risk (RR) = 0.64 (95% CI, 0.43-0.94), P = .02. The incidence of chronic GVHD did not differ significantly between the cohorts (P = .97). Two-year incidences of treatment-related mortality and relapse for matched versus mismatched were 14% (range, 9%-20%) versus 22% (range, 15%-29%) with P = .10 and 13% (range, 8%-19%) versus 18% (range, 10%-27%) with P = .40, respectively. Two-year adjusted leukemia-free survival (LFS) and overall survival were 71% (range, 63%-78%) versus 64% (range, 54%-73%) with P = .27 and 72% (range, 64%-79%) versus 71% (range, 62%-77%) with P = .72, respectively. Multivariate analyses showed that only advanced disease stage and a diagnosis of acute leukemia had increased risk of relapse, treatment failure, and overall mortality. In summary, HCT performed with related HLA-mismatched donors is a feasible approach with acceptable outcomes.

Acute Disease↗
PubMed2005

A strand-loop-strand structure is a possible intermediate in fibril elongation: long time simulations of amyloid-beta peptide (10-35).

A total of 6.2 micros molecular dynamics simulations of amyloid-beta (10-35) (Abeta) were performed in explicit water solvent. The results reveal that the collapsed-coil (cc) structure determined by experiments is stable at pH 5.6 for hundreds of nanoseconds, but it can exchange with a strand-loop-strand (SLS) structure on the microsecond time scale. The SLS structure has D23-K28 as a reverse loop and the central hydrophobic core and the C-terminal in hydrophobic contact. This SLS structure topologically resembles the proposed monomer conformation in fibrils. Since it has been suggested that a special conformation of Abeta is needed when the monomer binds to fibril ends to elongate fibrils, we propose that the SLS structure may be an important intermediate binding structure for Abeta fibril growth. Simulations at pH 2.0, which is used to mimic the mutation of E22Q and D23N, and at high temperature (400 K) indicate that the SLS structure is considerably populated under these conditions while the cc structure is disrupted. These results imply that the SLS structures may also be a binding intermediate in other conditions such as E22Q and/or D23N mutations and high temperature, which have been proved to promote fibril formation previously.

Amyloid beta-Peptides↗
PubMed2005

The time and spatial effects of bystander response in mammalian cells induced by low dose radiation.

Bystander effects induced by low dose of ionizing radiation have been shown to widely exist in many cell types and may have a significant impact on radiation risk assessment. Though many studies have been reported on this phenomenological observation, the mechanisms underlying this process are not clear, especially on the questions of how soon after irradiation the bystander effects can be initiated and how far this bystander signal can be propagated once it is started. DNA double-strand breaks (DSBs) induced by ionizing radiation or carcinogenic chemicals can be visualized in situ using gamma-H2AX immunofluorescent staining. Our previous studies have shown that in situ visualization of DSBs could be used to assess irradiation-induced extranuclear/extracellular (bystander) effect at an early stage after irradiation. In the present studies, we used this method to investigate the time and spatial effects of damage signals on unirradiated bystander cells. The results showed that increased DSBs in irradiated and unirradiated bystander areas could be visualized 2 min after radiation and reached its maximum 30 min after radiation. The average levels of DSB formation at 30 min post-1cGy irradiation in the irradiated and unirradiated bystander areas were 3-fold and 2-fold higher than those of the sham-irradiated control cells, respectively. Afterwards, the formation of DSBs declined with incubation time and remained steady for at least 6 h at a level that was statistically higher than their controls. The results also showed that the bystander signal derived from irradiated cells could be transferred to anywhere in the dish and the percentage of DSBs in the unirradiated bystander cells was not dependent on the dose delivered. Moreover, the fraction of DSB positive cells in unirradiated bystander areas showed a time-dependent increase based on its distance to the irradiated area at very early stage post-irradiation. Both lindane and DMSO significantly suppressed the yield of DSBs in the cells of unirradiated bystander areas, which suggest that gap junctional intercellular communication and reactive oxygen species played important roles in the induction of the bystander effects, both in irradiated and unirradiated bystander areas.

Bystander Effect↗
PubMed2005

Expression of MUC1 and its significance in hepatocellular and cholangiocarcinoma tissue.

AIM: To investigate the relation between MUC1 expression, distribution, and prognosis in hepatocellular and cholangiocarcinoma (HCC and CC) and cirrhotic liver tissues, and their significance in HCC and CC diagnosis. METHODS: Expression and distribution of MUC1 were examined by immunohistochemical assay with anti-MUC1 mAb in 59 samples of HCC and 37 samples of CC, 20 samples of cirrhotic liver tissues, and 10 samples of normal liver tissues, seeking possible associations between MUC1 positive expression, distribution in HCC and CC (primary liver cancer, PLC) cases and the studied clinical data. RESULTS: Immunohistochemical analysis of MUC1 expression showed that in the 96 PLC samples, 68 (70.8%) were strong positive, and 6 (6.2%) were weak positive. Only 4 in the 20 cirrhotic liver tissues were found to be weak positive, while no expression of MUC1 was detected in normal liver tissues. Apparently, the high expression rate of MUC1 in PLC tissues was statistically significant in comparison to that in cirrhotic and normal liver tissues. The expressed MUC1 protein, stained in dark brownish or brownish-yellow particles, chiefly localized on the cancer cell membranes or in cytoplasm. In the 68 strong positive samples, 40 were detected on cell membrane and the other 28 were in cytoplasm. In addition, follow-up studies of those PLC cases demonstrated that MUC1 expression on cell membrane or in cytoplasm was closely associated with PLC prognosis. The expression of MUC1 in PLC had little statistical significance in respect of the pathological types and sizes of the tumors, but a strong relationship regarding histological differentiation, metastasis of lymph nodes, portal canal emboli, and post-operational recurrence of the carcinomas. After 3 years of tumor excision, the metastasis rate in MUC1 positive expression group (67.6%) was much higher than that in MUC1 weak expression group (33.3%) and negative expression group (31.8%), and thus the survival rate in MUC1-positive expression group was significantly different from that in weak and negative expression groups. CONCLUSION: Expression and localization of MUC1 proteins in primary liver carcinomas (PLCs) may act as prognostic markers, and MUC1 molecules might be helpful in differential diagnosis.

Adult↗
PubMed2005

Cyclopentenone isoprostanes inhibit the inflammatory response in macrophages.

Although both inflammation and oxidative stress contribute to the pathogenesis of many disease states, the interaction between the two is poorly understood. Cyclopentenone isoprostanes (IsoPs), highly reactive structural isomers of the bioactive cyclopentenone prostaglandins PGA2 and PGJ2, are formed non-enzymatically as products of oxidative stress in vivo. We have, for the first time, examined the effects of synthetic 15-A2- and 15-J2-IsoPs, two groups of endogenous cyclopentenone IsoPs, on the inflammatory response in RAW264.7 and primary murine macrophages. Cyclopentenone IsoPs potently inhibited lipopolysaccharide-stimulated IkappaB alpha degradation and subsequent NF-kappaB nuclear translocation and transcriptional activity. Expression of inducible nitric-oxide synthase and cyclooxygenase-2 were also inhibited by cyclopentenone IsoPs as was nitrite and prostaglandin production (IC50 approximately 360 and 210 nM, respectively). 15-J2-IsoPs potently activated peroxisome proliferator-activated receptor gamma (PPARgamma) nuclear receptors, whereas 15-A2-IsoP did not, although the anti-inflammatory effects of both molecules were PPARgamma-independent. Interestingly 15-A2-IsoPs induced oxidative stress in RAW cells that was blocked by the antioxidant 4-hydroxy-TEMPO (TEMPOL) or the mitochondrial uncoupler carbonyl cyanide p-(trifluoromethoxy)phenylhydrazone. TEMPOL also abrogated the inhibitory effect of 15-A2-IsoPs on lipopolysaccharide-induced NF-kappaB activation, inducible nitricoxide synthase expression, and nitrite production, suggesting that 15-A2-IsoPs inhibit the NF-kappaB pathway at least partially via a redox-dependent mechanism. 15-J2-IsoP, but not 15-A2-IsoP, also potently induced RAW cell apoptosis again via a PPAR gamma-independent mechanism. These findings suggest that cyclopentenone IsoPs may serve as negative feedback regulators of inflammation and have important implications for defining the role of oxidative stress in the inflammatory response.

Active Transport, Cell Nucleus↗
PubMed2005

Organ-specific roles for transcription factor NF-kappaB in reovirus-induced apoptosis and disease.

Reovirus induces apoptosis in cultured cells and in vivo. In cell culture models, apoptosis is contingent upon a mechanism involving reovirus-induced activation of transcription factor NF-kappaB complexes containing p50 and p65/RelA subunits. To explore the in vivo role of NF-kappaB in this process, we tested the capacity of reovirus to induce apoptosis in mice lacking a functional nfkb1/p50 gene. The genetic defect had no apparent effect on reovirus replication in the intestine or dissemination to secondary sites of infection. In comparison to what was observed in wild-type controls, apoptosis was significantly diminished in the CNS of p50-null mice following reovirus infection. In sharp contrast, the loss of p50 was associated with massive reovirus-induced apoptosis and uncontrolled reovirus replication in the heart. Levels of IFN-beta mRNA were markedly increased in the hearts of wild-type animals but not p50-null animals infected with reovirus. Treatment of p50-null mice with IFN-beta substantially diminished reovirus replication and apoptosis, which suggests that IFN-beta induction by NF-kappaB protects against reovirus-induced myocarditis. These findings reveal an organ-specific role for NF-kappaB in the regulation of reovirus-induced apoptosis, which modulates encephalitis and myocarditis associated with reovirus infection.

Animals↗
PubMed2005

A human SARS-CoV neutralizing antibody against epitope on S2 protein.

An immune antibody phage-display library was constructed from B cells of SARS convalescent patients. More than 80 clones were selected from the library by using the whole inactivated SARS-CoV virions as target. One human scFv, B1, was characterized extensively. The B1 recognized SARS pseudovirus in vivo and competed with SARS sera for binding to SARS-CoV with high affinity (equilibrium dissociation constant, K(d) = 105 nM). The B1 also has potent neutralizing activities against infection by pseudovirus expressing SARS-CoV S protein in vitro. Finally, we found that the B1 recognized an epitope on S2 protein, especially within amino acids 1023-1189 of S2 protein. This study not only first made a human neutralizing antibody, which recognized an epitope on S2 protein like natural antibody in sera, but also may help us to better understand the immunological characteristics of SARS protein and SARS vaccine design.

Antibodies↗
PubMed2005

Expression, purification, and characterization of a neovasculature targeted rmhTNF-alpha in Escherichia coli.

The tumor vasculature is a suitable target for cancer treatment. RGD-4C (CDCRGDCFC) peptide can bind to human alphav integrins, which are known to be selectively expressed in human tumor blood vessels. Some studies showed that coupling anticancer drugs or peptides to the RGD peptides yielded compounds with increased efficacy against tumors and lowered toxicity to normal tissues in mice. TNF-alpha mutant (rmhTNF-alpha) that we previously constructed has been proved to have stronger antitumor effect compared with TNF-alpha. To increase antitumor effect and lower toxicity of rmhTNF-alpha, we coupled RGD4C to the N-terminal of rmhTNF-alpha (termed RGD4C-rmhTNF) and expressed RGD4C-rmhTNF in Escherichia coli. Here, we describe the expression, purification, and characterization of RGD4C-rmhTNF.

Animals↗
PubMed2005

[Allogeneic hematopoietic stem cell transplantation for treatment of Philadelphia chromosome positive acute lymphoblastic leukemia].

OBJECTIVE: To explore the optimal time of allogeneic hematopoietic stem cell transplantation (allo-HSCT) applied in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL), and the optimum order of donor selection. METHODS: From Mar 2000 to Jul 2004, 32 patients with Ph+ ALL were treated by Allo-HSCT, and the follow up ended at Dec 30.2004 with medium of 13 months. Of whom, 24 were male, and 8 were female. Twenty-three patients have been transplanted in CR1, 9 patients beyond CR1 (1 in CR2, 8 in refractory or relapse status). Twelve cases received HSCT from identical sibling donor, 4 unrelated Cord Blood Transplantation (CBT), 3 HSCT from matched unrelated donor (MUD), and 13 HSCT from mismatched related donor (MMRD), of which, 6 cases were M(BCR/ABL) subtype, and 20 m(BCR/ABL) subtype. The Kaplan-Meier method was used to estimate the probabilities of leukemia-free survival (LFS), overall survival (OS) and relapse incidence (RI), and the factors were compared by means of the Log-rank test. Simultaneous effect of multiple covariates were estimated with Cox model. RESULTS: Of all the 32 cases engrafted, 4-year OS was 57.19%, LFS 37.09%, and RI 56.36%. In univariate prognostic analysis model, the OS was higher in CR1 group pre-HSCT than that in non-CR1 group (74.50% vs 22.22%, P=0.0046), LFS was higher (49.06% vs 11.11%, P=0.0057), RI was lower (44.80% vs 84.76%, P=0.0157); the OS was higher in M(BCR/ABL) group than that in m(BCR/ABL) group (100% vs 40.91%, P=0.0318), LFS was higher (75% vs 17.72%, P=0.0057), RI was lower (25% vs 77.88, P=0.0116); OS was similar in HLA MM RD group to that in HLA identical group (52.65% vs 55.56%, P=0.6247), LFS was similar (45.12% vs 30.00%, P=0.8315), and RI was also similar (50.77% vs 60.62%, P=0.8217). In multiple covariate analysis model, the BCR/ABL type was the risk factor of LFS [P=0.005, Exp(B)=9.971] and RI (P=0.006, Exp(B)=9.488), the status of disease pre-HSCT and BCR/ABL subtype was the risk factor of OS [P was 0.010 and 0.038, Exp(B) was 4.532 and 37.537 respectively]. CONCLUSION: We had better do HSCT in CR1 to treat Ph+ ALL, if patient is refractory to chemotherapy, we can try STI571, and HSCT should be done as soon as possible if the patients get CR. Mismatched related donor is considered as regular donor for Ph+ ALL patients without identical donors. We should pay more attention to monitoring and prophylaxis of relapse in m(BCR/ABL) patients after HSCT.

Adolescent↗
PubMed2005

Identification of the cyclic-nucleotide-binding domain as a conserved determinant of ion-channel cell-surface localization.

Mutations of a putative cyclic-nucleotide-binding domain (CNBD) can disrupt the function of the hyperpolarization-activated cyclic-nucleotide-gated channel (HCN2) and the human ether-a-go-go-related gene potassium channel (HERG). Loss of function caused by C-terminal truncation, which includes all or part of the CNBD in HCN and HERG, has been related to abnormal channel trafficking. Similar defects have been reported for several of the missense mutations of HERG associated with long QT syndrome type 2 (LQT2). Thus, we postulate that normal processing of these channels depends upon the presence of the CNBD. Here, we show that removal of the entire CNBD prevents Golgi transit, surface localization and function of HERG channel tetramers. This is also true when any of the structural motifs of the CNBD is deleted, suggesting that deletion of any highly conserved region along the entire length of the CNBD can disrupt channel trafficking. Furthermore, we demonstrate that defective trafficking is a consequence of all LQT2 mutations in the CNBD, including two mutations not previously assessed and two others for which there are conflicting results in the literature. The trafficking sensitivity of the CNBD might be of general significance for other ion channels because complete deletion of the CNBD or mutations at highly conserved residues within the CNBD of the related ERG3 channel and HCN2 also prevent Golgi transit. These results broadly implicate the CNBD in ion-channel trafficking that accounts for the commonly observed loss of function associated with CNBD mutants and provides a rationale for distinct genetic disorders.

Amino Acid Sequence↗
PubMed2005

[Efficacy of intravenous administration of itraconazole on fungal infections in immunocompromised patients with hematological diseases].

OBJECTIVE: To investigate the efficacy of intravenous administration of itraconazole on fungal infections in immunocompromised patients with hematological diseases according to stratified diagnoses. METHODS: Twenty-five patients with hematological diseases who were diagnosed according to the criteria of European Organization for Research and Treatment of Cancer (EORTC), including 6 cases with confirmed diagnosis diagnosis, 12 cases with clinical diagnosis, and 7 cases with recommended diagnosis, underwent intravenous injection of itraconazole 125 approximately 200 mg bid for 2 days and then qd for at most 2 weeks and then oral administration of itraconazole 0.4 g/day for at most 2 weeks, and then the repeated regimen with a course of treatment of 1 approximately 3 months from 2002 to 2004. Eighteen cases were diagnosed with lung infection, 1 case with sinuses and trachea infection, and the infection sites were not documented for other 7 cases. The clinical results were analyzed. RESULTS: The effective rates of the patients with confirmed diagnosis, with clinical diagnosis, and with recommended diagnosis were 66.7% (4/6), 83.3% (10/12), and 14.3% (1/7) respectively. The effective rates of the patients with major imaging signs and those with secondary imaging signs were 90.0% (9/10) and 97.1% (4/7). There was a significant difference between the curative effects of the patients with confirmed diagnosis and those with recommended diagnosis (P = 0.006). CONCLUSION: Fungal infections in immunocompromised patients with hematological diseases can be successfully treated with intravenous administration of itraconazole.

Adolescent↗