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Biomedical subjects

M Zhang

Publications and source records attributed to M Zhang.

At least 73 records · Page 4Linked to original sources
PubMed2005

Activation of antitumor cytotoxic T lymphocytes by fusion of patient-derived dendritic cells with autologous osteosarcoma.

BACKGROUND AND AIM: Fusion of human dendritic cells (DCs) with tumor cells is an effective approach for delivering tumor antigens to DCs, and DC/tumor fusion cells are potent stimulators of autologous T cells. However, the integration and morphology of DC/osteosarcoma fusion cells has not been examined. This study was designed to investigate the antitumor effects of tumor vaccine produced by electrofusion between human osteosarcoma cells and DCs. METHODS: In the present study, we eletrofused patient-derived DCs to autologous osteosarcoma cells. The fusion cells possessed the properties of both patient cells. After electrofusion, the cytoplasm of the two cells was integrated, whereas their nuclei remained separate entities. The intracellular structure was observed on fusion cells under the transmission electron microscope. RESULTS: Coculture of patient-derived peripheral blood mononuclear cells (PBMC) with DC/tumor fusion cells resulted in activation of T cells as assessed by standard cytotoxic T lymphocytes (CTLs) assays. CONCLUSIONS: The present study provides valid evidence on integration of human DCs and tumor cells and links their properties to T cell activation. The fusion cells may thus represent a promising strategy for DC-based immunotherapy of patients with osteosarcoma.

Cancer Vaccines↗
PubMed2004

Hysteroscopy in the evaluation of patients with recurrent pregnancy loss: a cohort study in a primary care population.

BACKGROUND: The purpose of this study was to determine the prevalence of structural uterine defects (SUD) in patients with recurrent pregnancy loss (RPL) attending a large family medicine practice and to determine the effectiveness of the therapeutic intervention. METHODS: This prospective cohort study from October 1995 to October 1998 included 23 patients aged 23 to 35 years (mean, 28.1) with an otherwise unexplained history of three or more 1st- or 2nd-trimester miscarriages and no live births. None of the couples were tobacco or alcohol users, all of them and had normal cytogenetic examinations and testing. Their jobs were unrelated to chemical handling. All patients had a complete history taken and underwent physical examination and hysteroscopy with directed biopsy. They had normal values for complete blood count, sedimentation rate, urinalysis and culture (gonorrhea, Chlamydia, syphilis, hepatitis B, HIV), lupus anticoagulant, anticardiolipin antibodies, spermiogram, progesterone, and pelvic ultrasound. RESULTS: Fourteen patients (60.9%) had a normal hysteroscopy (with biopsies). Nine patients (39.1 %) had SUD, as follows: Five patients (21.8%) had intrauterine adhesions, two patients (8.7%) had a septated uterus, one patient (4.3%) had submucosal myoma, and one patient (4.3%) had multiple factors. After appropriate therapy of the SUD, seven patients (77.8%) achieved successful pregnancy and two patients (22.2%) had recurrent miscarriage. In the normal hysteroscopy group, eight patients (57.1%) had recurrent miscarriages, two patients (14.3%) had infertility, and four patients (28.6%) achieved successful pregnancy with no further therapy. CONCLUSIONS: The prevalence of SUD in our studied population was 39.1 %. After appropriate treatment, the rate of live-birth pregnancies in these patients was 77.8%. Because SUD are the most treatable cause of RPL, these patients should be identified early after other potential causes of RPL are eliminated.

Abortion, Habitual↗
PubMed2004

Repeated amphetamine couples norepinephrine transporter and calcium channel activities in PC12 cells.

Repeated intermittent amphetamine enhances efflux of dopamine through the dopamine transporter in rat basal ganglia and through the norepinephrine transporter in rat pheochromocytoma PC12 cells. Extracellular Ca2+ is required for the detection of this enhancement in the rat. In this study, we examined the role of Ca2+ and Ca2+ channels in the enhanced amphetamine-induced dopamine efflux that develops in PC12 cells following repeated intermittent amphetamine. Repeated pretreatment of PC12 cells with 1 microM amphetamine followed by a drug-free period increased amphetamine-induced efflux of dopamine compared with controls. The enhancement in amphetamine-induced dopamine efflux depended upon the presence of extracellular Ca2+ and was inhibited by the blockade of N-type and L-type Ca2+ channels. The enhanced dopamine efflux was not altered by tetanus toxin or reserpine, treatments that abrogate synaptic vesicle-mediated, exocytotic dopamine efflux. Measurement of intracellular Ca2+ concentrations using fura-2/acetoxymethyl ester revealed that amphetamine increased intracellular Ca2+ by a transporter-dependent mechanism. In amphetamine-pretreated cells, amphetamine elicited a greater increase in intracellular Ca2+; this increase depended upon the presence of extracellular Ca2+ and N- and L-type Ca2+ channel activity. The enhanced amphetamine-induced dopamine efflux requires Ca2+/calmodulin kinase activity. In vehicle-treated cells, 1 microM amphetamine inhibited the calmodulin kinase activity although it did not in amphetamine-pretreated cells. This study suggests that repeated intermittent amphetamine couples norepinephrine transporter activity and Ca2+ signaling.

Adrenergic Agents↗
PubMed2004

Genome diversity among regional populations of Francisella tularensis subspecies tularensis and Francisella tularensis subspecies holarctica isolated from the US.

Francisella tularensis is a highly infectious facultative intracellular pathogen that is considered a potential agent of bioterrorism. Four different F. tularensis subspecies have been identified and they appear to display different ecological and virulence characteristics as well as differences in geographical distribution. One simple explanation for the variation in ecological and virulence characteristics is that they are conferred by differences in genome content. To characterize genome content among stains isolated from United States, we have used a DNA microarray designed from a shotgun library of a reference strain. Polymorphisms distributed among polyphyletic sets of strains was the most common pattern of genome alteration observed, indicating that strain-specific genome variability is significant. Nonetheless, 13 different contiguous segments of the genome were found to be missing exclusively in each of the subsp. holarctica strains tested. All 13 are associated with repeat sequences or transposases that could promote insertion/deletion events. Comparison of the live vaccine strain to other holarctica strains also identified three regions that are absent exclusively in the live vaccine strain derived from holarctica.

Bacterial Vaccines↗
PubMed2004

Novel mutation, L371V, causing multigenerational Gaucher disease in a Lebanese family.

We have identified six individuals over three generations within a Lebanese-Arab family affected with Gaucher disease. This family is unusual and informative because affected members are homozygous for a previously unidentified mutation, L371V. Clinical symptoms begin in early childhood and progress to moderately severe involvement by young adulthood. There is significant anemia, thrombocytopenia, and bony involvement, but no mental deterioration. The phenotype is more severe than the phenotype observed in the common mutation associated with type 1 Gaucher disease, N370S. It is unknown whether L371V is a private mutation limited to this family, or will prove to be a common mutation within the Lebanese population.

Adolescent↗
PubMed2004

Chinese herbal medicines for type 2 diabetes mellitus.

BACKGROUND: Traditional Chinese herbal medicines have been used for a long time to treat diabetes, and many controlled trials have been done to investigate their efficacy. OBJECTIVES: To assess the effects of Chinese herbal medicines in patients with type 2 diabetes mellitus. SEARCH STRATEGY: We searched the following electronic databases: The Cochrane Library (CENTRAL), the Chinese BioMedical Database, MEDLINE, EMBASE, and LILACS, combined with hand searches on Chinese journals and conference proceedings. Date of last search was April 2004. No language restriction was used. SELECTION CRITERIA: Randomised trials of herbal medicines (with at least two months treatment duration) compared with placebo, pharmacological or non-pharmacological interventions were included. DATA COLLECTION AND ANALYSIS: Data were extracted independently by two reviewers. The methodological quality of trials was evaluated using the parameters of randomisation, allocation concealment, double blinding, and drop-out rates. Meta-analyses were performed where data were available. MAIN RESULTS: Sixty-six randomised trials, involving 8302 participants, met the inclusion criteria. Methodological quality was generally low. Sixty-nine different herbal medicines were tested in the included trials, which compared herbal medicines with placebo, hypoglycaemic drugs, or herbal medicines plus hypoglycaemic drugs. Compared with placebo, Holy basil leaves, Xianzhen Pian, Qidan Tongmai, traditional Chinese formulae (TCT), Huoxue Jiangtang Pingzhi, and Inolter showed significantly hypoglycaemic response. Compared with hypoglycaemic drugs including glibenclamide, tolbutamide, or gliclazide, seven herbal medicines demonstrated a significant better metabolic control, including Bushen Jiangtang Tang, Composite Trichosanthis, Jiangtang Kang, Ketang Ling, Shenqi Jiangtang Yin, Xiaoke Tang, and Yishen Huoxue Tiaogan. In 29 trials that evaluated herbal medicines combined with hypoglycaemic drugs, 15 different herbal preparations showed additional better effects than hypoglycaemic drugs monotherapy. Two herbal therapies combined with diet and behaviour change showed better hypoglycaemic effects than diet and behaviour change alone. No serious adverse effects from the herbal medicines were reported. REVIEWERS' CONCLUSIONS: Some herbal medicines show hypoglycaemic effects in type 2 diabetes. However, these findings should be carefully interpreted due to the low methodological quality, small sample size, and limited number of trials. In the light of some positive findings, some herbal medicines deserve further examination in high-quality trials.

Diabetes Mellitus, Type 2↗
PubMed2004

Micro-venous valves in the superficial veins of the human lower limb.

It is commonly believed that venous valves are not present in veins smaller than 2 mm in diameter. Venous valves, however, have been identified recently in small veins in several regions of the body. This study was undertaken to determine the size distribution of venous valves in the human lower limb micro-venous circulation. Vascular casts were made from six adult lower limbs and the sampled areas were viewed by scanning electron microscopy. In total, 2,376 valves were identified from 410 cm(3) of subcutaneous tissue. The vast majority (94%) of the valves were in veins less than 300 microm in luminal diameter, with 65% of the valves present in venous channels less than 100 microm in luminal diameter. The smallest valves identified were present in venous channels 18 microm in diameter. All valves were bicuspid and often associated with a tributary. Endothelial cells on the vein wall not associated with a valve were fusiform and arranged parallel to the long axis of the vessel, however, the endothelial cells on the luminal and valve sinus surfaces of the cusp were more polyhedral in shape and showed no obvious pattern of alignment. This study provides direct evidence to show that small superficial veins of the human lower limb do contain abundant venous valves and, for the first time, shows that the majority of these valves are present within venous channels less than 100 microm in luminal diameter.

Aged↗
PubMed2004

Prenatal echocardiographic differential diagnosis of fetal cardiac tumors.

OBJECTIVES: To present data on echocardiographic findings of fetal cardiac tumors and discuss their differential diagnoses. METHODS: We retrospectively reviewed 14 cases of fetal echogenic cardiac mass diagnosed between 1990 and 2003; 12 were confirmed to be cardiac tumors and two were false-positive diagnoses. The echocardiographic characteristics examined included number, size, location and associated complications. RESULTS: Eight fetuses had a single tumor and four fetuses had multiple tumors. The left ventricle was most often affected. Parents of eight fetuses opted for termination of pregnancy, one fetus died in utero and three affected fetuses survived. Histopathological examination revealed cardiac rhabdomyoma in six fetuses, fibroma in two, teratoma in two, lipoma in one and hemangioma in one. The pitfalls associated with prenatal echocardiographic diagnosis of cardiac tumors include: they may be too small to be visualized, intracardiac echogenic foci may mimic tumors, and echogenicity resulting from extracardiac structures or neoplasms near the heart may falsely appear as tumors. CONCLUSION: Fetal cardiac tumors can be detected by echocardiography. However, differential diagnosis is important as this will affect prognosis and subsequent management.

Diagnosis, Differential↗
PubMed2004

Bone mass and lifestyle related factors: a comparative study between Japanese and Inner Mongolian young premenopausal women.

The purpose of this study was to evaluate the ethnic difference in bone mass between Japanese and Inner Mongolian young premenopausal women and to assess the contribution of lifestyle related and anthropometric factors to bone mass. We studied 33 Japanese and 44 Inner Mongolian healthy young women, aged 20-34 years, in urban area. Speed of sound (SOS), broadband ultrasound attenuation (BUA) and stiffness index (SI) were measured at the calcaneus using quantitative ultrasound (QUS) analysis. Age at menarche, regularity of menstruation and lifestyle related factors were estimated by a self-reported questionnaire. There were no differences between the two groups in age, height, weight, BMI, regularity of menstruation, frequency of meat intake, frequency of yellow-green vegetable intake and exercise habit. Japanese women had significantly lower age at menarche and higher proportion of milk consumption habit at junior high school, senior school and present. Before adjustment, Japanese women had significantly higher SOS and SI than Inner Mongolian women. However, after adjustment for age at menarche and milk consumption habit at junior high school, both of which were significantly different between groups, no group-differences remained in either SOS or SI. These results suggest that the differences in age at menarche and milk consumption habit at junior high school, which relate to hormonal and nutritional status during puberty, may account for the differences in bone mass between Japanese and Inner Mongolian young women.

Adult↗
PubMed2004

Biphasic calcium phosphate nanocomposite porous scaffolds for load-bearing bone tissue engineering.

A novel biodegradable nanocomposite porous scaffold comprising a beta-tricalcium phosphate (beta-TCP) matrix and hydroxyl apatite (HA) nanofibers was developed and studied for load-bearing bone tissue engineering. HA nanofibers were prepared with a biomimetic precipitation method. The composite scaffolds were fabricated by a method combining the gel casting and polymer sponge techniques. The role of HA nanofibers in enhancing the mechanical properties of the scaffold was investigated. Compression tests were performed to measure the compressive strength, modulus and toughness of the porous scaffolds. The identification and morphology of HA nanofibers were determined by X-ray diffraction and transmission electron microscopy, respectively. Scanning electron microscopy was used to examine the morphology of porous scaffolds and fracture surfaces to reveal the dominant toughening mechanisms. The results showed that the mechanical property of the scaffold was significantly enhanced by the inclusion of HA nanofibers. The porous composite scaffold attained a compressive strength of 9.8 +/- 0.3 MPa, comparable to the high-end value (2-10 MPa) of cancellous bone. The toughness of the scaffold increased from 1.00+/-0.04 to 1.72+/-0.02 kN/m, as the concentration of HA nanofibers increased from 0 to 5 wt %.

Biocompatible Materials↗
PubMed2004

Synthesis, characterisation, activities, cell uptake and DNA binding of [[trans-PtCl(NH3)2] [mu-(H2N(CH2)6NH2)] [trans-PdCl(NH3)2](NO3)Cl.

The dinuclear complex: [[trans-PtCl(NH(3))(2)] [mu-(H(2)N(CH(2))(6)NH(2))] [trans-PdCl(NH(3))(2)](NO(3))Cl (code named DHD) has been synthesized and characterized. The activity against human cancer cell lines including ovarian: A2780, A2780(cisR), cell up take, level of binding with DNA and nature of interaction of the compound with pBR322 plasmid and salmon sperm DNAs have been determined. The compound is found to exhibit significant anticancer activity against ovarian cancer cell lines: A2780, A2780(cisR) and A2780(ZD0473R)--about two times as active as cisplatin against A2780 cell line, about five times as active as cisplatin against A2780(cisR) and A2780(ZD0473R) cell lines. The higher activity of DHD suggests that the compound is able to overcome multiple mechanisms of resistance operating in A2780(cisR) and A2780(ZD0473R) cell lines. DHD is believed to form a range of interstrand GG adducts with duplex DNA that induces global changes in the DNA conformation, unlike cisplatin and ZD0473 that form mainly intrastrand adducts that induces a local kink in a DNA strand. Increasing prevention of BamH1 digestion of form I and form II pBR322 plasmid DNA with the increase in concentration of DHD provides support to the idea that the interstrand binding of DHD with pBR322 plasmid DNA brings about global changes in DNA conformation.

Animals↗
PubMed2004

Ca(2+)-calmodulin signalling pathway up-regulates GABA synaptic transmission through cytoskeleton-mediated mechanisms.

We investigated the role of calcium (Ca(2+))/calmodulin (CaM) signaling pathways in modulating GABA synaptic transmission at CA1 pyramidal neurons in hippocampal slices. Whole-cell pipettes were used to record type A GABA receptor (GABA(A)R)-gated inhibitory postsynaptic currents (IPSCs) and to perfuse intracellularly modulators in the presence of glutamate receptor antagonists. GABA(A)R-gated IPSCs were enhanced by the postsynaptic infusions of adenophostin (1 microM), a potent agonist of inositol-1,4,5-triphosphate receptor (IP(3)R) that induces Ca(2+) release. The enhancement was blocked by co-infusing either 1,2-bis(2-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid (10 mM) or CaM-binding peptide (100 microM). Moreover, the postsynaptic infusion of Ca(2+)-CaM (40/10 microM) enhanced both evoked and spontaneous GABA(A)R-gated IPSCs. The enhancement was attenuated by co-infusing 100 microM CaM-KII(281-301), an autoinhibitory peptide of CaM-dependent protein kinases. These results indicate that postsynaptic Ca(2+)-CaM signaling pathways essentially enhance GABAergic synaptic transmission. In the investigation of synaptic targets for the enhancement, we found that IP(3)R agonist-enhanced GABA(A)R-gated IPSCs were attenuated by co-infusing colchicine (30 microM), vincristine (3 microM) or cytochalasin D (1 microM) that inhibits tubulin or actin polymerization, implying that actin filament and microtubules are involved. We conclude that postsynaptic Ca(2+)-CaM signaling pathways strengthen the function of GABAergic synapses via a cytoskeleton-mediated mechanism, probably the recruitment of receptors in the postsynaptic membrane.

Animals↗
PubMed2004

Prevention of hepatitis B virus reinfection after orthotopic liver transplantation.

OBJECTIVE: We discuss the prevention of hepatitis B virus reinfection following orthotopic liver transplantation. METHODS: Sixty-eight cases of chronic fulminant hepatitis B, the end stage of liver cirrhosis and liver carcinoma complicated with HBV cirrhosis, were given antiviral drugs pre- and posttransplantation to prevent hepatitis B virus reinfection. Lamivudine was administered to two cases and lamivudine + HBIG to 63 cases. Adefovir + HBIG was administered to three cases. The serum HBV, HBV DNA, liver biopsy immunohistochemistry and clinical examinations were performed. RESULTS: One of two cases given lamivudine developed reinfection with serum HBSAg, HbeAb, HBcAb, HBV DNA, and positive and liver biopsy immunohistochemistry showing HBSAg phenotype. Two of the 63 cases given lamivudine + HBIG developed reinfection with serum HBSAg, HBeAb, HBcAb positive and liver biopsy immunohistochemistry showing HBSAg phenotype. The serum HBV DNA was positive in one of the two cases. Three cases given adefovir developed no reinfection with HBV. CONCLUSION: Orthotopic liver transplantation is an effective treatment for HBV infection; lamivudine + HBIG or adefovir + HBIG prevent hepatitis B virus reinfection.

Adult↗
PubMed2004

Transforming growth factor-beta (TGF-beta) protein levels are not elevated in the blood or bile of patients with primary sclerosing cholangitis: a pilot study.

Primary sclerosing cholangitis (PSC) is a chronic cholestatic disorder of unknown etiology characterized by progressive fibrosis and stricturing of the biliary tract. Transforming growth factor-beta (TGF-beta) is a family of cytokines produced by biliary tract epithelial cells that promote fibrinogenesis. Our objective was to determine whether TGF-beta levels are increased in the blood and/or bile of PSC patients compared to patients with other causes of obstructed biliary tracts (controls). Serum and bile TGF-beta levels were documented by enzyme-linked immunoassay in 10 adult PSC and 10 control patients obtained at the time of endoscopic retrograde cholangiography. Serum and bile TGF-beta levels were similar in the two groups (PSC versus control sera, 33.4 +/- 4.3 versus 27.5 +/- 7.7 ng/ml, and bile, 367 +/- 275 versus 457 +/- 247 ng/mg, respectively). Serum and bile TGF-beta levels are not increased in patients with PSC. Hence, the results of this pilot study do not support the hypotheses that PSC is caused by dysregulated TGF-beta expression.

Alkaline Phosphatase↗
PubMed2004

IL-18 gene therapy develops Th1-type immune responses in Leishmania major-infected BALB/c mice: is the effect mediated by the CpG signaling TLR9?

IL-18 regulates either Th1 or Th2 responses depending on the cytokine microenvironment. Administration of recombinant IL-18 (rIL-18) alone does not promote Th1 response, but rather induces Th2 response and exacerbates Leishmania major infection in susceptible BALB/c mice. Here, we treated BALB/c mice with an IL-18-expressing plasmid by using a gene gun weekly after L. major infection. This gene therapy resulted in improved pathogenic process and preferential induction of Th1 responses by inducing the expression of IL-12 p40, but treatment with rIL-18 did not. Notably, simultaneous administration of rIL-18 with an empty plasmid vector rendered BALB/c mice resistant to the infection, despite the fact that treatment with either rIL-18 alone or the plasmid vector alone did not influence the susceptibility. The synergistic role of the vector with rIL-18 was found to depend on CpG motifs, which enhanced expression of proinflammatory cytokines, especially IL-12, from APCs through Toll-like receptor (TLR) 9 ligation. Treatment with methylated plasmid vector in which CpG was disrupted could no longer prevent the disease development in coadministration with rIL-18. Taken together, IL-18 gene therapy was shown to develop Th1-type protective immunity in L. major-infected BALB/c mice without the requirement of exogenous IL-12, probably via CpG-TLR9 signaling pathway.

Animals↗
PubMed2004

Flavonoids from Radix Scutellariae as potential stroke therapeutic agents by targeting the second postsynaptic density 95 (PSD-95)/disc large/zonula occludens-1 (PDZ) domain of PSD-95.

Excessive activation of N-methyl-D-aspartate receptors (NMDARs) and subsequent production of nitric oxide by neuronal nitric oxide synthase (nNOS) contribute to neuronal damage resulting from hypoxic and ischemic insults. NMDARs and nNOS are coupled together at the postsynaptic membrane through their interaction with postsynaptic density protein (PSD) 95 via PSD-95/disc large/zonula occludens-1 (PDZ) domains. We used NMR (nuclear magnetic resonance) spectroscopy to screen medicinal herbs used in traditional Chinese medicine (TCM) stroke therapy for compounds binding to the second PDZ domain (PDZ2) of PSD-95, the domain linking nNOS and PSD-95. Aqueous extract of Huangqin, the root of Scutellaria baicalensis Georgi (Labiatae), showed significant binding to PDZ2 of PSD-95. The binding site of the active components in the extract overlapped with the nNOS/NR2B-binding pocket of PDZ2 of PSD-95. Four flavones, baicalin, norwogonoside, oroxylin A-glucuronide (oroxyloside), and wogonoside were isolated and found to account for the PDZ-binding activity of the extract. NMR titration experiments showed that baicalin and norwogonoside displayed the highest PDZ2 binding affinity, while oroxylin A-glucuronide and wogonoside showed 4-5 fold less potency in binding to the PDZ domain. Identification of the PDZ binding activity of these compounds will allow investigating whether or not it contributes to the observed clinical effects of Radix Scutellariae. Furthermore, these molecules might provide leads for the development of drugs targeting the signaling pathways mediated by PDZ domains.

Animals↗