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Biomedical subjects

Z Zheng

Publications and source records attributed to Z Zheng.

At least 163 records · Page 9Linked to original sources

[En bloc vein resection in the treatment of pancreatic tumors adherent to the superior mesenteric-portal vein confluence].

Contraindication is often considered to pancreaticoduodenectomy for patients with malignant tumors of the pancreatic head. From 1989 through 1995, 15 patients with tumors of the pancreatic head adherent to the superior mesenteric-portal vein confluence (SMPV) underwent pancreaticoduodenectomy with en bloc resection of SMPV. There was no perioperative mortality. Follow-up data showed a mean survival of 17.1 months among 7 deaths, which was significantly longer than an average of 3.8 months among previous 17 patients who abandoned radical resection (P < 0.001). We consider that pancreaticoduodenectomy with en bloc resection of SMPV is feasible in some cases.

Aged↗

Analysis on the therapeutic effect of combined use of acupuncture and mediation in 297 cases of male sterility.

Of the 279 cases of male sterility treated by the combination of acupuncture, pilose antler essence injection to acupoints and oral administration of Chinese materia medica, 142 cases (47.8%) were cured, 81 cases (27.3%) markedly effective, 53 cases (17.8%) effective and 21 cases (7.1%) ineffective. The therapeutic effect of the combination of these three treatments was satisfactory.

Acupuncture Points↗

[Suicide gene therapy for glioma using HSV-tk/GCV system].

OBJECTIVE: To establish a suicide gene therapy system HSV-tk/GCV for glioma treatment in vitro as well as in vivo and test its efficacy. METHODS: C6 rat glioma cells were infected with recombinant retrovirus containing HSV-tk gene. Following selection the C6/tk cell line which stably expressed tk was cloned. The sensitivities of C6/tk cells to several nucleoside analogues, such as GCV, BVdU, ACV, were compaired by the growth inhibition studies. Antitumor effects were also observed after GCV treatment in nude mice bearing tumors derived from C6/tk cells. RESULTS: The growth inhibition studies showed that GCV was the most efficient prodrug, and C6/tk cells were highly sensitive to GCV, with an IC50 < 0.2 mumol/L, being 500-fold less than that in tk-negative C6 cells. In vivo studies showed similar results. Significant tumor inhibition was found in the treatment group. CONCLUSION: Tumor cells expressing HSV-tk gene can be eradicated by administration of GCV in vitro as well as in vivo.

Animals↗

[Model-based study of time-dependent coronary blood flow distribution in left ventricular wall and its dependences on coronary pressure driving force].

The proposed model is of use for understanding the mechanism of intramyocardial circulation. There are three classical myocardial vascular nets in the model; each net has four vessel-size compartments which are characterized by time-dependent nonlinear resistance and compliance. The experimentally measured timed-varying perfusion and left ventricular pressure sources are used as driving inputs for the circulation. The phasic coronary blood flow characteristics predicted by the model exhibit waveform patterns that correlate qualitatively with the generally accepted results. In addition, more work is made about the myocardial infusion which is essentially controlled by the coronary pressure driving force. The results make it clear that the Intra-aortic balloon pumping and External counterpulsation are conducive to the balance between supply and demand of coronary blood flow.

Coronary Circulation↗

Transformation by Wnt family proteins correlates with regulation of beta-catenin.

Several members of the Wnt family of secreted factors are strongly implicated as regulators of mammary cell growth and differentiation. To investigate Wnt signaling in mammary cells, we have assessed the abilities of 10 different Wnt genes to cause transformation of C57MG mammary epithelial cells and in parallel studied their effects on beta-catenin, a component of the Wnt-1 signaling pathway. Autocrine transforming potential was tested by expression of Wnt proteins in C57MG cells, and paracrine effects were evaluated by coculture of C57MG cells with fibroblasts secreting different Wnt proteins. Western blotting confirmed the expression of each Wnt protein in the relevant cell lines. Activities of the 10 Wnts tested were divisible into three groups. Wnt-1, Wnt-2, Wnt-3, and Wnt3a induced strong transformation and an elongated refractile cell morphology. Wnt-6 and Wnt-7a produced weak morphological changes. Wnt-4, Wnt-5a, Wnt-5b, and Wnt-7b had no effect at all on C57MG morphology. Analysis of beta-catenin levels showed that the transforming Wnts induced accumulation of cytosolic beta-catenin, whereas nontransforming Wnts did not. These result demonstrate that several Wnt family members are capable of elevating beta-catenin levels and suggest that their signaling pathways share intracellular signaling components. The correlation between increased cytosolic beta-catenin levels and C57MG transformation supports a role for beta-catenin in transformation of these cells. These data also imply the existence of receptors that respond to certain Wnt proteins but not to others.

Animals↗

[Localization and expression of dopamine receptors in stomach and duodenum in rats].

UNLABELLED: Dopamine is an important neurotransmitter which may contribute to the regulation of gastrointestinal function, but its mechanism remains elusive. OBJECTIVE: The existence, localization and expression of dopamine receptor mRNAs in rat stomach and duodenum were examined by in situ hybridization. METHODS: The oligonucleotide probes were selected and synthesized according to the previous work. All the probes were labelled with alpha S35dATP using the terminal deoxynucleotide transferase, then were hybridized with the frozen, fixed preparation of rat stomach and duodenum. The density of silver granules were counted and analyzed by the image analysis computer system. RESULTS: It was found that all five subtypes of dopamine receptor mRNAs existed in the stomach and duodenum with greatly different expression. The distribution of dopamine mRNAs in the stomach were mainly localized in the lamina propria near the lamina muscularis mucosae and parallel to the longitudinal axis of the tract. Whereas, all five MRNAs were spread over the entire layer of the duodenal mucosa. With the image analysis system, abundant expressing levels of D5 and D4 mRNAs were documented unexpectedly. CONCLUSION: All these results suggest that dopamine produced its effect via dopamine receptors especially D5 subtype and D4 receptor might be act as a modulator.

Animals↗

[The application of intracoronary stenting to type B and C lesions of coronary arteries].

Intracoronary stenting was introduced to 4 lesions due to coronary arterial dissections and to 2 lesions owing to elastic recoil of coronary arteries and stent placement was directly performed in 6 complex coronary lesions after 12 target lesions from 7 patients with Types B and C lesions of coronary arteries had been pre-dilated with balloon. Coronary angiography showed that dissections and recoils had disappeared. Target lesions were well dilated and blood flow was well improved in all cases, one patient was complicated with hemorrhage which was cured quickly. During the follow-up period of 1 to 24 months, another case had recurrence of angina after 2 months of stenting which could be controlled with anti-angina agents. These indicate that intracoronary stenting had good therapeutic effect and is considered as a safe, fast and effective method in dealing with acute complications of coronary artery after routine PTCA.

Aged↗

Changes in poly(A) tail length of arginine vasotocin messenger ribonucleic acid in the hypothalamus of water-deprived chickens.

The effects of water deprivation on the secretion of vasotocin (AVT) and expression of the AVT gene were studied in White Leghorn cockerels. Animals deprived of water for 4 days were compared with normally hydrated controls. Blood samples were obtained for measurements of plasma osmolality and AVT levels, and the hypothalamus was collected for extraction of total cellular RNA. A 519-bp AVT cDNA was prepared by reverse transcriptase-polymerase chain reaction and a 209-bp PstI/EcoRI restriction fragment from the 3' region of the fowl AVT cDNA was used as a probe for Northern blot analysis. Plasma osmolality and AVT levels in dehydrated birds were about 30 and 350% greater, respectively, than those in normally hydrated controls. The quantity of hypothalamic AVT mRNA was 2. 3-fold greater in water-deprived birds compared to controls. The size of the hypothalamic AVT transcript was about 100-bp longer in the water-deprived birds. As determined by RNase H treatment in the presence and absence of oligo(dT)12-18, the increase in mean size of the AVT mRNA in dehydrated animals was due to a longer poly(A) tract. Our results indicate that osmotic stress up-regulates expression of the AVT gene and increases the accumulation of AVT mRNA in the hypothalamus. This accumulation may, in part, be due to lengthening of the AVT mRNA poly(A) tail which is a general mechanism associated with stabilization of vertebrate mRNAs.

Animals↗

Results of a double-blind placebo-controlled study of the double-stranded RNA drug polyI:polyC12U in the treatment of HIV infection.

In this multicenter, randomized, double-blind study the activity of polyI:polyC12U administered with zidovudine was evaluated in the treatment of HIV infection. Thirty-six HIV-positive, pre-AIDS individuals (100-500 CD4+ cells/mm3) who had had at least six months of zidovudine therapy received polyI:polyC12U (400 or 700 mg) or placebo twice weekly with zidovudine. PolyI:polyC12U subjects with baseline CD4+ counts > or = 300/mm3 showed a trend towards reduced CD4+ loss versus placebo recipients. PolyI:polyC12U subjects were more likely to exhibit positive delayed-type hypersensitivity responses than placebo recipients. Placebo subjects crossing over to polyI:polyC12U therapy demonstrated improved CD4+ and delayed-type hypersensitivity responses. PolyI:polyC12U subjects with baseline CD4+ counts > or = 300/mm3 were less likely to develop AIDS than similar placebo subjects. PolyI:polyC12U therapy of HIV-positive subjects restored or stabilized immune function as indexed by delayed-type hypersensitivity reactivity and, in individuals with CD4+ counts > 300/mm3, abrogated CD4+ loss and reduced disease progression. PolyI:polyC12U was generally well-tolerated in this zidovudine-treated population. No subject discontinued therapy due to an adverse reaction or aberrant laboratory parameter.

Acquired Immunodeficiency Syndrome↗

Two distinct binding sites for globotriaosyl ceramide on verotoxins: identification by molecular modelling and confirmation using deoxy analogues and a new glycolipid receptor for all verotoxins.

BACKGROUND: The Escherichia coli verotoxins (VTs) can initiate human vascular disease via the specific recognition of globotriaosyl-ceramide (Gb3) on target endothelial cells. To explore the structural basis for receptor recognition by different VTs we used molecular modelling based on the crystal structure of VT1, mutational data and binding data for deoxy galabiosyl receptors. RESULTS: We propose a model for the verotoxin 'cleft-site complex' with Gb3. Energy minimizations of Gb3 within the 'cleft site' of verotoxins VT1, VT2, VT2c and VT2e resulted in stable complexes with hydrogen-bonding systems that were in agreement with binding data obtained for mono-deoxy analogues of Gb3. N-deacetylated globoside (aminoGb4), which was found to be a new, efficient receptor for all verotoxins, can be favourably accommodated in the cleft site of the VTs by formation of a salt bridge between the galactosamine and a cluster of aspartates in the site. The model is further extended to explain the binding of globoside by VT2e. Docking data support the possibility of an additional binding site for Gb3 on VT1. CONCLUSIONS: The proposed models for the complexes of verotoxins with their globoglycolipid receptors are consistent with receptor analogue binding data and explain previously published mutational studies. The results provide a first approach to the design of specific inhibitors of VT-receptor binding.

Bacterial Toxins↗

Mutations in the carboxyl-terminal hydrophobic sequence of human cytomegalovirus glycoprotein B alter transport and protein chaperone binding.

Human cytomegalovirus glycoprotein B (gB) plays a role in the fusion of the virion envelope with the host cell membrane and in syncytium formation in infected cells. Hydrophobic sequences at the carboxyl terminus, amino acids (aa) 714 to 771, anchor gB in the lipid bilayer, but the unusual length of this domain suggests that it may serve another role in gB structure. To explore the function(s) of this region, we deleted aa 717 to 747 (gB deltaI mutation), aa 751 to 771 (gB deltaII mutation), and aa 717 to 772 (gB deltaI-II mutation) and constructed a substitution mutation, Lys-748 to Val (Lys748Val)-Asn749Ala-Pro750Ile (gB KNPm). Mutated forms of gB were expressed in U373 glioblastoma cells and subjected to analysis by flow cytometry, confocal microscopy, and immunoprecipitation. Mutations gB deltaI-II and gB deltaII alone caused secretion of gB into the medium, confirming that aa 751 to 771 function as a membrane anchor. In contrast, mutations gB deltaI and gB KNPm blocked cell surface expression and arrested gB transport in the endoplasmic reticulum (ER). Detailed examination of gB deltaI and gB KNPm with a panel of monoclonal antibodies showed that the mutated forms were indistinguishable from wild-type gB in conformation and formed oligomers; however, they remained sensitive to endoglycosidase H and did not undergo endoproteolytic cleavage. Analysis of protein complexes formed by gB and molecular chaperones in the ER showed that calnexin and calreticulin, lectin-like chaperones, bound equal amounts of uncleaved wild-type gB, gB deltaI, and gB KNPm, but the glucose-regulated proteins 78 (BiP) and 94 formed stable complexes only with the mutated forms, causing their retention in the ER. Our studies show that aa 714 to 750 are key residues in the architecture of gB molecules and that the ER chaperones, which facilitate gB folding and monitor the quality of glycoproteins, detect subtle changes in folding intermediates that are conferred by mutations in this region.

Amino Acid Sequence↗

Accessory human cytomegalovirus glycoprotein US9 in the unique short component of the viral genome promotes cell-to-cell transmission of virus in polarized epithelial cells.

Human cytomegalovirus (CMV) encodes accessory glycoproteins that are dispensable for virus growth in nonpolarized cells in culture. We report that CMV deletion mutants lacking the gene for accessory glycoprotein US9 in the unique short component of the viral genome are impaired in plaque formation in polarized human retinal pigment epithelial (ARPE-19) cells. Comparison of CMV deletion mutants in US9 with herpes simplex virus type 1 deletion mutants lacking glycoproteins gE and gI showed that both of these mutants are impaired in altering junctional complexes and increasing paracellular permeability in polarized ARPE-19 cells cultured on permeable filter supports. Results of functional studies indicate that CMV US9 and homologs of gE have analogous roles in promoting virus spread across lateral membranes of polarized epithelial cells.

Animals↗

Preparation, cloning, and high level expression in E. coli of interleukin 2-pseudomonas exotoxin fusion genes.

Using PCR and oligonucleotide-directed mutagenesis, recombinant plasmids which express IL2-PE fusion genes, e.g., IL2-PE40, IL2-PE40 KDEL, IL2-PE66(4Glu), and IL2-PE66(4Glu) KDEL, were constructed and expressed in E. coli at a high level. The fusion proteins were 20-30% of the total soluble bacterial proteins, existing as inclusion bodies in the host cell. In addition, there are single EcoRI, PstI, and SmaI restriction sites at the 5', 3' terminals and the linking region of the fusion genes, respectively, in the constructed expression plasmids so that these vectors could be conveniently converted to other expression vectors containing other cytokines or toxins.

ADP Ribose Transferases↗

[Monoamine concentrations in experimental ulcers in rats].

A high performance liquid chromatography with electrochemical detection (HPLC-ECD method was employed for determination of monoamines, including epinephrine (E), norepinephrine (NE), 3,4-dihydroxyphenylacetic acid (DOPAC), dopamine (DA), 5-hydroxy-3-indole acetic acid (5HIAA), homovallilic acid (HVA) and 5-hydroxytryptamine (5HT), in body, antrum and duodenal mucosa of normal rats and rats with MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) induced ulcers. Abundant contents of DA and DOPAC were emerging in normal gastric body, antrum and duodenal mucosa while subsequent reduction of DA concentration were observed in gastric body and duodenal mucosa of rats by MPTP intracerebroventricular injection and persisted for a long time. The degree of reduction was correlated with time and dosage of MPTP administered. The decrease of 5HT in gastric body and its increase in duodenum were also observed at the same time. Such variation of concentrations implied that DA might play an important role in the pathogenesis of ulcerous diseases and 5HT might probably contribute to the development of ulcers.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Dynamics of tryptophan binding to Escherichia coli Trp repressor wild type and AV77 mutant: an NMR study.

Binding of L-tryptophan to Escherichia coli trp repressor wild type (WT) and AV77 mutant was studied by 1H NMR spectroscopy. Ligand binding to the proteins resulted in changes in line widths and chemical shifts of ligand resonances, but no changes in the coupling constant were observed. Line width and chemical shift changes of the H4 L-tryptophan proton were monitored as a function of temperature and ligand and protein concentrations. For the WT repressor, the H4 proton displays slow exchange at low temperatures (20-35 degrees C), while fast exchange occurs in the range from 45 to 65 degrees C. From 35 to 40 degrees C, the range of intermediate exchange, lines are broadened beyond detection. For the AV77 mutant, the intermediate and fast exchange regions are shifted at least 5 degrees C to higher temperatures. Line shapes of L-tryptophan H4 proton resonances were simulated using a general expression based on McConnell's modified Bloch equations for a two-site exchange. From the simulations, an exchange frequency (upsilon exch) of about 3000 Hz was obtained at 45 degrees C for WT and about 1000 Hz for AV77 mutant. The activation energy for the process is 32.7 kcal K-1 mol-1 for the WT and 29.1 kcal K-1 mol-1 for AV77. At 45 degrees C, the dissociation and association rate constants (k-1 and K+1, respectively) were calculated to be 2.0 x 10(3) s-1 and 9.9 x 10(6) M-1 s-1, for the WT.(ABSTRACT TRUNCATED AT 250 WORDS)

Bacterial Proteins↗

Glycosylation of CD44 negatively regulates its recognition of hyaluronan.

Although CD44 is expressed on a wide variety of cell types, few of them use it to recognize the ligand hyaluronan (HA). A glycosylation-defective clone of Chinese hamster ovary cells (Lec 8) bound HA, demonstrating that complete processing of glycoproteins with addition of a full complement of sialic acid is not required. On the contrary, subsequent findings revealed that complex sugars on CD44 can actually inhibit ligand recognition. Two subclones of wild-type Chinese hamster ovary cells with similar amounts of surface CD44 were isolated on the basis of HA binding and found to differ with respect to CD44 size as well as staining with fluorescent lectins. Treatment of the nonbinding clone with tunicamycin reduced the size of the protein and allowed the cells to recognize HA via CD44. This function was also induced by treatment with deglycosylating enzymes (either a mixture of endoglycosidase F and N-glycosidase F or neuraminidase alone). A possible role for glycosylation in regulation of adhesion was then sought with a series of normal and transformed murine cells. Disruption of glycosylation or treatment with deglycosylating enzymes did not induce ligand binding in an interleukin 7-dependent pre-B cell line, and splenic B cells also appeared to be in an inactive state. Some normal B cells acquired the ability to recognize HA after stimulation with lipopolysaccharide or interleukin 5 and had distinctive surface characteristics (loss of immunoglobulin D and acquisition of CD43). An additional subset of activated cells might have been in a transitional state, because the cells bound ligand after neuraminidase treatment. The ligand-binding ability of a purified CD44-immunoglobulin fusion protein dramatically increased after neuraminidase treatment. Thus, differential glycosylation of this molecule is sufficient to influence its recognition function. Cell adhesion involving HA can be regulated by multiple mechanisms, one of which involves variable glycosylation of CD44.

Animals↗