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Biomedical subjects

Q Zhu

Publications and source records attributed to Q Zhu.

At least 127 records · Page 7Linked to original sources

[Isolation of a gene related to trichosanthin-induced apoptosis (GRETA)].

Disturbance of the apoptosis-related signaling pathway is regarded as one of the critical factors for tumorigenesis. Isolation of the genes involved in the process of apoptosis would be thereby helpful to explore the mechanism of tumor transformation and to develop novel therapeutic approaches. Here we report a gene fragment GRETA, the gene related to trichosanthin-induced apoptosis, isolated from a leukemia cell line U937 undergoing apoptosis induced by a plant protein Trichosanhin (TCS). A 293bp segment of GRETA was revealed to be 78.3% homologous to Bruton's tyrosine kinase at nucleic acid level. And Northern blot analysis showed that three messengers of RNA with the size of about 0.8-kb, 2.0-kb and 7.0-kb, respectively, were detected in TCS-untreated U937 cells when probed with GRETA, but there were only 0.8-kb and 2.0-kb transcripts appeared in apoptotic U937 cells. In addition, the abundance of each transcript changed apparently. The 0.8-kb transcript, for example, was the main band in Northern analysis in apoptotic U937 cells while was only detected marginally in TCS-untreated cells. These data suggested a possible relationship between the alternative splicing patterns of GRETA and the apoptosis.

Apoptosis↗

[Study on the IR and UV dual-spectrum radiation].

The article gives a method to produce dual spectrum radiation in IR and UV. Relying on theoretical analysis, the relative data are computed, some atomic materials are selected and added to a double-base propellants. When the UV pyrotechnics is ignited together with traditional IR pyrotechnics, the spectrum of IR and UV is emitted at the same time. The final measuring curves show that all results are satisfying.

English Abstract↗

Enhanced immune response to the melanoma antigen gp100 using recombinant adenovirus-transduced dendritic cells.

Glycoprotein 100 (gp100) is one of a series of well-characterized human melanoma-associated antigens expressed by most melanoma cells. Immunization of C57BL/6 mice with an adenovirus (Ad) vector encoding human gp100 (Adhgp100) has been shown to induce limited protective immunity against challenge with murine melanoma B16 cells. In the current study we determined whether gp100-specific immunity can be enhanced using bone-marrow-derived dendritic cells (DCs) transduced with Adhgp100 ex vivo. Subcutaneous injection of Adhgp100-infected DCs resulted in potent T-cell-mediated protective immunity and a greater than 80% reduction of established tumors when administered to B16 tumor-bearing hosts. Compared to direct injection of Adhgp100 vector alone, immunization with Adhgp100-infected DCs induced markedly greater antitumor activity. In vitro CTL analysis demonstrated that DC-Adhgp100 immunization activated both CD4(+) and CD8(+) CTLs, while no lytic activity was generated by vaccination with Adhgp100 alone. In vivo depletion of CD4(+) T cells, but not CD8(+) T cells, completely abrogated CTL activity, suggesting that Adhgp100-transduced DCs result in activation of both CD4(+) and CD8(+) CTLs via a CD4(+)-dependent mechanism. We speculate that this improved efficacy of Adhgp100-transduced DCs compared to direct immunization with Adhgp100 may be the result of direct DC-mediated CD4(+) T cell activation. These results emphasize the importance of CD4(+) T cells in the development of therapeutic antigen-specific cancer vaccines.

Adenoviridae↗

Extended half-life and elevated steady-state level of a single-chain Fv intrabody are critical for specific intracellular retargeting of its antigen, caspase-7.

8 h) and high steady-state levels of protein accumulation, while the H2 intrabodies had a half-life of 2 h and less protein at steady state. These results suggest that the choice of sFv as an intrabody depends critically on the intracellular sFv protein having an extended half-life and elevated steady-state level. Thus, extended half-life must be considered together with sFv antibody specificity and affinity when choosing an optimal sFv intrabody for functional studies of cellular proteins.

Animals↗

[Detection of human papillomavirus and herpesvirus genotypes in biopsy specimens from cervical carcinoma by PCR-endonuclease cleavage].

OBJECTIVE: This study was to detect the human papillomavirus (HPV) and herpes simplex virus (HSV) genotypes in biopsy specimens of cervical carcinoma and genital verruca by PCR-endonuclease cleavage. METHODS: Biopsy samples of were obtained from 390 patients with cervical carcinoma, HPV and HSV genotypes were detected by PCR and endonuclease cleavage. RESULTS: The results indicated that HPV types 16, 18, 35 were found in 152 (38.9%) of 390 cervical carcinoma, in 56 (31.8%) of 176 cervical erosion, while HPV types 6, 11 were found in 80 (58.8%) of 136 acuminate erruca. The HSV-2 type were found in 135 (34.6%) of 390 cervical carcinoma and in 33 (18.7%) of 176 cervical erosion. The HPV 16, 18, 35 types and HSV-2 type found in normal cervical secretions of the control group all were 3.2%, There was significant difference between the test group of cervical carcinoma and the control group of normal cervical secretion (P < 0.001 by x 2 analysis). The restriction endonuclease analysis of these amplified products showed that positive rates of HPV 16, 18, 35 types and HSV-2 type from cervical carcinoma were 23.3%, 14.6%, 1.0% and 34.6%, respectively. While HPV 6, 11 types from acuminate verruca were 36.0% and 22.8% positive respectively. CONCLUSION: The results suggest that HPV 16, 18 types and HSV-2 type are associated with majority of the cervical carcinoma.

Adult↗

Membrane topology and cell surface targeting of microsomal epoxide hydrolase. Evidence for multiple topological orientations.

Microsomal epoxide hydrolase (mEH) is a bifunctional membrane protein that plays a central role in the metabolism of xenobiotics and in the hepatocyte uptake of bile acids. Numerous studies have established that this protein is expressed both in the endoplasmic reticulum and at the sinusoidal plasma membrane. Preliminary evidence has suggested that mEH is expressed in the endoplasmic reticulum (ER) membrane with two distinct topological orientations. To further characterize the membrane topology and targeting of this protein, an N-glycosylation site was engineered into mEH to serve as a topological probe for the elucidation of the cellular location of mEH domains. The cDNAs for mEH and this mEH derivative (mEHg) were then expressed in vitro and in COS-7 cells. Analysis of total expressed protein in these systems indicated that mEHg was largely unglycosylated, suggesting that expression in the ER was primarily of a type I orientation (Ccyt/Nexo). However, analysis, by biotin/avidin labeling procedures, of mEHg expressed at the surface of transfected COS-7 cells, showed it to be fully glycosylated, indicating that the topological form targeted to this site originally had a type II orientation (Cexo/Ncyt) in the ER. The surface expression of mEH was also confirmed by confocal fluorescence scanning microscopy. The sensitivity of mEH topology to the charge at the N-terminal domain was demonstrated by altering the net charge over a range of 0 to +3. The introduction of one positive charge led to a significant inversion in mEH topology based on glycosylation site analysis. A truncated form of mEH lacking the N-terminal hydrophobic transmembrane domain was also detected on the extracellular surface of transfected COS-7 cells, demonstrating the existence of at least one additional transmembrane segment. These results suggest that mEH may be integrated into the membrane with multiple transmembrane domains and is inserted into the ER membrane with two topological orientations, one of which is targeted to the plasma membrane where it mediates bile acid transport.

Amino Acid Sequence↗

No requirement of alpha-internexin for nervous system development and for radial growth of axons.

Alpha-Internexin is a type IV intermediate filament protein that is expressed abundantly in neurons during development of the peripheral and central nervous systems as well as in few neurons of the adult central nervous system. It has been suggested that alpha-internexin may act as a scaffold for the formation of neuronal intermediate filaments during early development. In addition, recent reports suggest that alpha-internexin could play a major role in two degenerative neurological disorders. We report here an analysis of mice with a targeted disruption of alpha-internexin gene. Unexpectedly, alpha-internexin -/- mice developed normally and did not exhibit overt phenotypes. Moreover, the absence of alpha-internexin did not interfere with neurite extension of cultured DRG neurons. The number and caliber of L4 ventral root axons remained unchanged in alpha-internexin -/- mice. In the retina, alpha-internexin begins to be expressed in retinal ganglion cells when their first axons reach the optic chiasma. Using HRP tracer, we show that the projection pattern of the RGC axons is not modified by the absence of alpha-internexin. Electron microscopy did not reveal significant differences in axonal calibers, in myelination of axons and in neurofilament structures between alpha-internexin -/- and control mice during development and at adult stage. These data indicate that alpha-internexin is not required for the polymerization of neurofilament in vivo. Mice deficient for both alpha-internexin and neurofilament light chain (NF-L) exhibited no over phenotypes as well. No intermediate filament structures were detectable in optic nerve of alpha-internexin -/-; NF-L -/- mice. Ours results do not support the hypothesis of a role for type IV intermediate filaments in axonal outgrowth during development of nervous system.

Age Factors↗

Interpreting patterns of gene expression with self-organizing maps: methods and application to hematopoietic differentiation.

Array technologies have made it straightforward to monitor simultaneously the expression pattern of thousands of genes. The challenge now is to interpret such massive data sets. The first step is to extract the fundamental patterns of gene expression inherent in the data. This paper describes the application of self-organizing maps, a type of mathematical cluster analysis that is particularly well suited for recognizing and classifying features in complex, multidimensional data. The method has been implemented in a publicly available computer package, GENECLUSTER, that performs the analytical calculations and provides easy data visualization. To illustrate the value of such analysis, the approach is applied to hematopoietic differentiation in four well studied models (HL-60, U937, Jurkat, and NB4 cells). Expression patterns of some 6,000 human genes were assayed, and an online database was created. GENECLUSTER was used to organize the genes into biologically relevant clusters that suggest novel hypotheses about hematopoietic differentiation-for example, highlighting certain genes and pathways involved in "differentiation therapy" used in the treatment of acute promyelocytic leukemia.

Animals↗

Future of bradyarrhythmia therapy systems: automaticity.

Since the first fixed-rate ventricular pacemaker was introduced in the late 1950s, pacing systems have evolved rapidly. Current developments focus on making devices more sophisticated and less complex--a challenging combination. Automaticity features such as beat-by-beat capture verification, sensitivity threshold adaptation, and algorithms to govern dynamically the maximum sensor rate have either recently been introduced or are likely to be introduced in the near future. Technologic advances are likely to allow meaningful improvements in current drain, battery performance, memory capacity, signal processing, telemetry, and programmer interface. Bradyarrhythmia therapy devices of the future promise to go beyond the pacemaker. Ultimately, pacing systems will become part of integrated cardiac rhythm management systems.

Bradycardia↗

Traumatic instabilities of the cervical spine caused by high-speed axial compression in a human model. An in vitro biomechanical study.

STUDY DESIGN: Traumatic injury of the cervical spine was produced on human cadavers and evaluated with instability tests and radiographs. OBJECTIVE: To relate traumatic injuries of the cervical spine to instability and patterns of traumatic injury to different levels of impact energy. SUMMARY OF BACKGROUND DATA: Data from young human cadavers are rare in traumatic models of the cervical spine, and instabilities caused by axial compression with different impacts remain unknown. METHODS: Fourteen cervical spine specimens (C2-C4) obtained from fresh human cadavers were divided evenly into two groups and subjected to axial compressive impact with 30 J and 50 J impact energy, respectively. Pure moments in flexion-extension, left/right lateral bending, and left/right axial rotation were applied to each specimen before and after trauma. The maximum moment was 2.0 Nm in each case. Ranges of motion and neutral zones were measured using stereophotogrammetry. RESULTS: Ranges of motion and neutral zones for both groups increased after trauma. No bony injury was observed on the radiographs after trauma with 30 J, but motions increased significantly in flexion, extension, and axial rotation. All specimens showed bony injuries after trauma with 50 J, whereas motions continued to increase significantly in all directions. The relative neutral zone values were larger than the corresponding range of motion values, except in flexion-extension after trauma with 50 J. CONCLUSIONS: The injury patterns of the cervical spine were associated with impact energy, and a high level of impact energy could produce either three-column injury or anterior middle-column injury. Instabilities of the cervical spine caused by compressive trauma increased with the level of impact energy. The neutral zone was more sensitive than the range of motion in representing spinal instability, whereas instability testing was more sensitive than radiographs in evaluating traumatic injury of cervical spine.

Adult↗

The pleckstrin homology domain of the Wiskott-Aldrich syndrome protein is involved in the organization of actin cytoskeleton.

In this study, we investigated the role of the pleckstrin homology (PH) domain of the Wiskott-Aldrich syndrome protein (WASP) in the regulation of actin cytoskeleton, which is defective in patients with Wiskott-Aldrich syndrome (WAS) and X-linked thrombocytopenia (XLT). Overexpression of the WASP in COS-7 cells cultured in the presence of fetal calf serum (FCS) resulted in large cluster formation of polymerized actin and WASP in the cytoplasm. In contrast, when the WASP transfected cells were cultured in the absence of FCS, activation with PMA or EGF was required to induce cluster formation. Overexpression of WASP with a missense mutation in the N-terminus of the PH domain failed to induce the large cluster formation in COS-7 cells even in the presence of FCS. We also found that phosphatidylinositol 4,5-bisphosphate (PIP(2)), which is known to regulate the actin cytoskeleton, binds to the PH domain of WASP, and the binding was abolished by the introduction of a missense mutation into the N-terminus but not the C-terminus of the PH domain. Together with the observations that most of the missense mutations observed in patients with WAS and XLT are located within the PH domain, these results indicate that the PH domain of WASP plays important roles in the regulation of actin cytoskeleton and suggested that the binding of PIP(2) to the PH domain is necessary for WASP to function properly.

Actins↗

A key role for GAP-43 in the retinotectal topographic organization.

To have a proper spatial visual perception, vertebrate retinal ganglion cells connect to their brain targets in a highly ordered fashion. The molecular bases for such topographic retinotectal connection in mammals still remain largely unknown. Using the gene knock-out approach in mice, we report here a key role for the GAP-43 growth cone protein in the development of the visual system. In mice bearing a targeted disruption of GAP-43 exon 1, a high proportion of retinal ganglion cell (RGC) axons was found to grow abnormally into the ipsilateral optic tract and into the hypothalamus. After leaving the optic chiasm during development, the GAP-43-deficient RGC axons generally follow the optic tracts but are unable to form proper terminal zones in the lateral geniculate nucleus. Moreover, in the superior colliculus, RGC axons lacking GAP-43 are intermingled. These results suggest an essential role for GAP-43 in development of the topographic retinotectal connection.

Animals↗

Cytotoxic evaluation of root-end filling materials in cultures of human osteoblast-like cells and periodontal ligament cells.

The cytotoxicity of three root-end filling materials (amalgam, IRM, and Super-EBA) was evaluated in cultures of human periodontal ligament cells and human osteoblast-like cells. Ten-millimeter-long plastic test tubes were filled with 3 mm of freshly mixed root-end filling materials at one end (1.5 mm diameter). The opposite end was sealed and attached by heat to a 35-mm cell culture dish. Human periodontal ligament cells and human osteoblast-like cells were seeded in the dishes. The size of cell-free zones around the root-end filling materials and the total cell number per dish were calculated after 3 and 7 days. Empty test tubes used as controls did not influence the growth and distribution of the cultured cells. Cell density increased in all groups in the test period. Amalgam had a larger cell-free zone, compared with IRM and Super-EBA and showed a reduction in total cell number per dish for both tested cell types. IRM and Super-EBA also had a cell-free inhibition zone for both cell types, but no significant reduction in total cell number per dish. This study showed that amalgam had a higher cell toxicity to human periodontal ligament cells and human osteoblast-like cells than IRM and Super-EBA.

Analysis of Variance↗

Disruption of type IV intermediate filament network in mice lacking the neurofilament medium and heavy subunits.

To clarify the role of the neurofilament (NF) medium (NF-M) and heavy (NF-H) subunits, we generated mice with targeted disruption of both NF-M and NF-H genes. The absence of the NF-M subunit resulted in a two- to threefold reduction in the caliber of large myelinated axons, whereas the lack of NF-H subunits had little effect on the radial growth of motor axons. In NF-M-/- mice, the velocity of axonal transport of NF light (NF-L) and NF-H proteins was increased by about two-fold, whereas the steady-state levels of assembled NF-L were reduced. Although the NF-M or NF-H subunits are each dispensable for the formation of intermediate filaments, the absence of both subunits in double NF-M; NF-H knockout mice led to a scarcity of intermediate filament structures in axons and to a marked approximately twofold increase in the number of microtubules. Protein analysis indicated that the levels of NF-L and alpha-internexin proteins were reduced dramatically throughout the nervous system. Immunohistochemistry of spinal cord from the NF-M-/-;NF-H-/- mice revealed enhanced NF-L staining in the perikaryon of motor neurons but a weak NF-L staining in axons. In addition, axonal transport studies carried out by the injection of [35S]methionine into spinal cord revealed after 30 days very low levels of newly synthesized NF-L proteins in the sciatic nerve of NF-M-/-;NF-H-/- mice. The combined results demonstrate a requirement of the high-molecular-weight subunits for the assembly of type IV intermediate filament proteins and for the efficient translocation of NF-L proteins into the axonal compartment.

Animals↗

Lignan and phenylpropanoid glycosides from Lancea tibetica and their antitumor activity.

A new lignan glucoside, the first 7,9'-monoepoxyte-trahydrofuran type lignan with the cis-relationship of H-7 and H-8, named tibeticoside (1), as well as ten known compounds have been isolated from the medicinal plant (roots, stems and leaves) Lancea tibetica. The structure of tibeticoside (1) has been elucidated on the basis of chemical and spectral evidence, especially by 2D-NMR (1H-1H COSY, HMQC, HMBC, NOESY). In addition, sylvatesmin (6) exhibited effective antitumor activity on B16 cells.

Animals↗

Origin of the suppression of chloride ion sensitivity in human embryonic hemoglobin Gower II.

The molecular origin of the observed reduction of chloride ion sensitivity in the oxygen binding characteristics of the human embryonic hemoglobin Gower II has been probed by using site-directed mutant forms of the protein. Separate mutation of the three amino acids previously identified as candidates for the suppression of chloride sensitivity in the epsilon chain allowed us to unambiguously identify the His beta 77-->epsilon Asn as the origin of the lower sensitivity towards chloride ions in hemoglobin Gower II, which allows oxygen exchange from the mother to the late embryo under physiological conditions.

Adult↗

Primary choledochorrhaphy after common bile duct exploration.

AIM: To prove further the safety of primary closure of the common bile duct. METHOD: Twenty patients among 99 common bile duct explorations underwent primary closure. Pre- and postoperative liver function test, ultrasound and intraoperative cholangiography data, operation time, postoperative complications and the length of postoperative stay were recorded. RESULTS: Nineteen patients did not suffer any biliary complication. One had bile leakage and bile peritonitis, and another had duodenal leakage. One case was complicated by gastric ulcer perforation. The mean postoperative hospital stay except for the 2 patients with complications was 8.72 +/- 0.75 days. Preoperative abnormal liver function tests recovered within 2-3 weeks after the operation. Postoperative ultrasound scan of the biliary tract within 2 months revealed no stenosis and residual stone. CONCLUSION: Primary common bile duct closure is a safe alternative to routine biliary drainage in selected patients.

Adult↗