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Biomedical subjects

J Zhu

Publications and source records attributed to J Zhu.

At least 325 records · Page 18Linked to original sources
PubMed1999

"Dip-Pen" nanolithography

A direct-write "dip-pen" nanolithography (DPN) has been developed to deliver collections of molecules in a positive printing mode. An atomic force microscope (AFM) tip is used to write alkanethiols with 30-nanometer linewidth resolution on a gold thin film in a manner analogous to that of a dip pen. Molecules are delivered from the AFM tip to a solid substrate of interest via capillary transport, making DPN a potentially useful tool for creating and functionalizing nanoscale devices.

Journal Article↗
PubMed1999

Novel BTB/POZ domain zinc-finger protein, LRF, is a potential target of the LAZ-3/BCL-6 oncogene.

BTB/POZ-domain C2H2 zinc(Zn)-finger proteins are encoded by a subfamily of genes related to the Drosophila gap gene krüppel. To date, two such proteins, PLZF and LAZ-3/BCL-6, have been implicated in oncogenesis. We have now identified a new member of this gene subfamily which encodes a 62 kDa Zn-finger protein, termed LRF, with a BTB/POZ domain highly similar to that of PLZF. Both human and mouse LRF genes, which localized to syntenic chromosomal regions (19p13.3 and 10B5.3, respectively), were widely expressed in adult tissues and cell lines. At approximately 9.5-10.0 days of embryonic development, the mouse LRF gene was expressed in the limb buds, pharyngeal arches, tail bud, placenta and neural tube. The LRF protein associated in vivo with LAZ-3/BCL-6, but not with PLZF to which it was more related. Although the LRF, or LAZ-3/BCL-6, BTB/POZ domain could readily homodimerize, no heterodimerization was detected in vivo between the LRF and LAZ-3/BCL-6 BTB/POZ domains and interaction between full length LRF and LAZ-3/BCL-6 required the presence of both the BTB/POZ domain and Zn-fingers in each partner protein. As expected from the above results, LRF and LAZ-3/BCL-6 also colocalized with each other in the nucleus. Taken together, our findings suggest that BTB/ POZ-domain Zn-finger proteins may function as homo and heterodimeric complexes whose formation, and hence the resultant effect on transcription of their downstream target genes, is determined by the levels and expression domains of a given partner protein.

Amino Acid Sequence↗
PubMed1999

Characterization of replication-competent adenovirus isolates from large-scale production of a recombinant adenoviral vector.

Replication-deficient adenoviral vectors have been developed for the delivery of DNA sequences encoding a variety of proteins intended for the management of disease through gene therapy. One concern is the occurrence of replication-competent adenovirus (RCA) in the population of replication-deficient adenoviral vectors as a result of recombination or contamination. To address this concern, it is necessary to determine the frequency of occurrence and to fully characterize the molecular structure and biological infectivity of RCA. rAd/p53 is a pIX-deleted p53 gene therapy vector that is designed to lower the RCA occurrence and to deliver the tumor suppressor gene p53 for treatment of various cancers. Multiple preparations of the replication-deficient adenoviral vector rAd/p53 were tested for the presence of RCA, employing a sensitive biological assay. Single plaques from RCA-positive preparations of rAd/p53 were isolated for molecular characterization. All of the RCA isolates displayed a single unique structure that contains the complete E1 sequence of adenovirus type 5 but lacks the p53 sequence. The detailed sequence analysis of the RCA suggests that it is most likely generated as a result of recombination events between the rAd/p53 DNA and the 293 host adenoviral sequence. Results from viral infectivity analysis by flow cytometry demonstrate no substantial difference in infectivity of RCA, rAd/p53, and wild-type adenovirus type 5 in 293 cells.

Adenovirus E1A Proteins↗
PubMed1999

T cell independence of bleomycin-induced pulmonary fibrosis.

The role of T cells and cytokines in bleomycin (BLM)-induced fibrosis was evaluated in susceptible and resistant strains of normal and SCID mice. Histology and hydroxyproline analysis showed that BLM induced pulmonary fibrosis in C57BL/6 and (C57BL/6 x BALB/c)F1 mice, whereas BALB/c mice were resistant to the disease. To test whether lymphocytes were required for the induction of BLM-induced pulmonary fibrosis, SCID mice were injected intratracheally with BLM and evaluated for the development of pulmonary inflammation and fibrosis. Similar morphological changes and increases in hydroxyproline were observed in both C57BL/6 SCID and (C57BL/6 x CB.17)F1 SCID animals compared to those seen in wild-type C57BL/6 and (C57BL/6 x BALB/c)F1 mice. In contrast, CB.17 SCID mice, which are genetically similar to BALB/c mice, were resistant to disease induction. Analysis of the cellular infiltrate in BLM-treated C57Bl/6 SCID mice confirmed a lack of T cells in the lungs of SCID mice and demonstrated a pronounced accumulation of eosinophils in areas of developing pulmonary fibrosis. NK cells were significantly elevated in untreated SCID mice and did not increase further after BLM treatment. Analysis of selected cytokines 1 day after initiation of BLM-induced pulmonary fibrosis indicated that the levels of TNF-alpha and IFN-gamma appeared to segregate with fibrosis in both the SCID and wild-type mice. The data demonstrate that T cells are not required for the induction of fibrosis by BLM and suggest that responses by non-lymphoid cells may be sufficient for the induction of fibrosis.

Animals↗
PubMed1999

Nasal administration of recombinant rat IL-4 ameliorates ongoing experimental autoimmune neuritis and inhibits demyelination.

Experimental autoimmune neuritis (EAN) is a CD4(+)T cell-mediated demyelinating disease of the peripheral nervous system (PNS) and serves as an experimental model for human immune-demyelinating neuropathies. In this study, we examined the effect of recombinant rat interleukin-4 (rrIL-4) on chronic EAN in Lewis rats induced by immunization with P0 peptide 180-199 and complete Freund's adjuvant (CFA). We estimated that nasal administration of rrIL-4, in dose ranges of 0.1-1 microg/rat/day in the initial phase of EAN, decreased the severity and the duration of clinical EAN. Hyporesponsiveness of T cells, downregulation of Th1 cell responses (INF-gamma), but increased levels of specific IgG1 isotypes document that nasal administration of rrIL-4 was systemically immune effective. Low grade inflammation and complete lack of regional demyelination within the sciatic nerves were seen in rrIL-4 treated rats. Based on these observations we suggest that nasal administration of IL-4 could be further evaluated, considering its possible use in human immune-demyelinating neuropathies.

Administration, Intranasal↗
PubMed1999

Apoptotic effect of outer-membrane proteins from Campylobacter jejuni on chicken lymphocytes.

Campylobacter jejuni is a significant cause of food-borne diseases in humans. The bacterium is considered a commensal organism in chickens, and it can heavily colonize chickens without causing inflammation. Poultry may be the major reservoir for the human infection in developed countries. Here we show that an outer-membrane protein extract prepared from the bacteria caused apoptosis of chicken lymphocytes detected in vitro with the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay that preferentially labels individual apoptotic cells. Blood- and spleen-lymphocytes from different-aged chickens displayed a significantly greater percentage of apoptotic cells after culture with the outer-membrane proteins from C. jejuni than controls treated with phosphate-buffered saline, chicken ovalbumin, or outer-membrane proteins prepared from E. coli strain BL21. The C. jejuni extract also produced apoptosis of chicken lymphoblastoid tumor cell lines. Apoptosis was blocked by pretreating the extract with proteinase K or antiserum against outer-membrane proteins. The results suggest that C. jejuni may be capable of achieving immune avoidance in chickens by causing apoptosis of lymphocytes.

Age Factors↗
PubMed1999

Rapamycin inhibits hepatic stellate cell proliferation in vitro and limits fibrogenesis in an in vivo model of liver fibrosis.

BACKGROUND & AIMS: The accelerated course of hepatic fibrosis that occurs in some patients after liver transplantation is a major clinical problem. This response may be caused by the antirejection therapeutics, and in an earlier report we showed that FK-506 enhanced the fibrogenic process in in vivo and in vitro models of liver fibrosis. In the present study, the aim was to determine whether a new immunosuppressive agent, rapamycin, enhances or inhibits liver fibrosis. METHODS: Effects of rapamycin were investigated in a carbon tetrachloride model of hepatic fibrosis in rats and on hepatic stellate proliferation in vitro. RESULTS: Rapamycin inhibited extracellular matrix deposition in the rat model of fibrogenesis as determined by histological analysis, collagen content, messenger RNA levels of procollagen and transforming growth factor beta1, and tissue transglutaminase activity. Moreover, rapamycin decreased platelet growth factor-induced proliferation of hepatic stellate cells. CONCLUSIONS: These findings indicate that the new antirejection agent rapamycin inhibits hepatic fibrosis and thus may become a valuable addition to the immunosuppression armamentarium.

Animals↗
PubMed1999

Radiosensitization of a mouse tumor model by sustained intra-tumoral release of etanidazole and tirapazamine using a biodegradable polymer implant device.

BACKGROUND AND PURPOSE: Drug toxicities are often a limiting factor in long term treatment regimes used in conjunction with radiotherapy. If the drug could be localized to the tumor site and released slowly, then optimal, intra-tumoral drug concentrations could be achieved without the cumulative toxicity associated with repeated systemic drug dosage. In this paper we describe the use of a biodegradable polymer implant for sustained intra-tumoral release of high concentrations of drugs targeting hypoxic cells. MATERIALS AND METHODS: The RIF-1 tumor was implanted subcutaneously or intramuscularly in C3H mice and irradiated with 60Co gamma rays. The drug delivery device was the co-polymer CPP-SA;20:80 into which the drug was homogeneously incorporated. The hypoxic radiosensitizer Etanidazole or the bioreductive drug Tirapazamine were delivered intra-tumorally by means of implanted polymer rods containing the drugs. Tumor growth delay (TGD) was used as the end point in these experiments. RESULTS: Both Etanidazole and Tirapazamine potentiated the effects of acute and fractionated radiation in the intra-muscular tumors but neither drug was effective in sub-cutaneous tumors. Since both drugs target hypoxic cells we hypothesized that the lack of effect in the subcutaneous tumor was attributable to the smaller size of the hypoxic fraction in this tumor model. This was confirmed using the hypoxia marker EF5. CONCLUSIONS: These results indicate that the biodegradable polymer implant is an effective vehicle for the intra-tumoral delivery of Etanidazole and Tirapazamine and that, in conjunction with radiation, this approach could improve treatment outcome in tumors which contain a sub-population of hypoxic, radioresistant cells.

Animals↗
PubMed1999

Sequence comparison of the L2 and S10 genes of bluetongue viruses from the United States and the People's Republic of China.

Bluetongue virus (BTV) infection of ruminants is endemic throughout much of the US and China. The S10 and a portion of the L2 gene segments of Chinese prototype strains of BTV serotypes 1, 2, 3, 4, 12, 15, and 16 were sequenced and compared to the same genes of prototype and field strains of BTV from the US. Phylogenetic analysis of the S10 gene segregated the Chinese viruses into a monophyletic group distinct from the US viruses, whereas similar analysis of the L2 gene segregated strains of BTV according to serotype, regardless of geographic origin.

Bluetongue virus↗
PubMed1999

Effects of chronic treatment with (+)-nicotine on the stress-induced hypertension and downregulation of central nicotinic receptors in rats: comparative study with (-)-nicotine.

The effects of chronic treatment with (+)-nicotine on the immobilization stress-induced changes in blood pressure, body weight, and [3H]cytisine binding to brain nicotinic receptors were examined in rats and were compared with those of (-)-nicotine. Immobilization stress (2 hr/day(-1), for 2 weeks) induced a moderate elevation of blood pressure, loss of body weight gain, and downregulation of [3H]cytisine binding sites in cerebral cortex and midbrain. Chronic treatment with (+)- or (-)-nicotine inhibited the stress-induced hypertension but did not suppress the inhibition of body weight gain by stress. Body weight before stress load was also reduced by (-)-nicotine but not (+)-nicotine treatment. Treatment with each isomer increased the maximum number of [3H]cytisine binding sites (Bmax) of brain stem, cerebral cortex, and hippocampus. The Bmax in midbrain was also increased by (+)-nicotine but not by (-)-nicotine. Stress-induced downregulation in cerebral cortex was inhibited by both isomers. These results suggest that (+)- and (-)-nicotine cause various effects, including anti-stress effect, on the central nervous system in rats, which are slightly different between the isomers.

Alkaloids↗
PubMed1999

Total synthesis and conformational studies of hapalosin, N-desmethylhapalosin and 8-deoxyhapalosin.

Hapalosin (2), a 12-membered cyclic depsipeptide possessing MDR-reversing activity, and analogues (3) and (4) have been synthesized using macrolactamization as an important ring-forming step. Three building blocks: (2S,3R)-3-(tert-butyldimethylsilyloxy)-2-methyl-decanoic acid (13), benzyl (S)-2-hydroxy-3-methylbutanate (14), and (4S,3R)-4-(benzyloxycarbonyl-methylamino)-3-methoxymethoxy-5-pheny l-pentanoic acid (28) were prepared from Evans's chiral imide (9), L-valine, and L-N-Boc phenylalanine (17), respectively, and were assembled together by applying twice Yamaguchi's coupling methodology. A new and efficient selective N-methylation of gamma-hydroxy-beta-amino ester taking advantage of the vicinal amino alcohol function was uncovered in the course of this study. Thus, treatment of compound 19 with HCHO in the presence of catalytic amount of pTsOH followed by reduction (NaBH3CN, TFA, CH2Cl2) of the so-formed oxazolidine 24 gave the N-methylated product 25. Furthermore, a dual role of oxazolidine as protecting group of vicinal amino alcohol and latent N-methyl function was established which allowed synthesizing both hapalosin (2) and N-desmethylhapalosin (3) from the same linear precursor 32 in a step-efficient and atom economic way. In contrast to hapalosin (2) and N-desmethyl analogue (3), the amide bond of 8-deoxy hapalosin (4) exists at room temperature (CDCl3) exclusively in s-cis conformation as evidenced by NOE studies. This observation has been explained on the basis of computational studies. No significant MDR reversing activity of 8-deoxy hapalosin (4) was observed in K562 R and S/Adriblastine against human erythroleucemic cell lines indicating thus the important contribution of hydroxy group to the bioactivity of hapalosin.

Depsipeptides↗
PubMed1999

Ultrasonically guided inferior vena cava stent placement: experience in 83 cases.

PURPOSE: Traditionally, inferior vena cava (IVC) stent placement is performed with fluoroscopic guidance. The object of this study was to evaluate use of ultrasound (US) as guidance for IVC stent placement for the management of Budd-Chiari syndrome. MATERIALS AND METHODS: Eighty-three patients with IVC membranous stenosis (n = 30), membranous occlusion (n = 19), segmental stenosis (n = 21), or segmental occlusion (n = 13) underwent IVC recanalization, balloon dilation, and stent placement under US guidance. Among the 83 patients, 67 had at least one patent hepatic vein, while 16 patients had three occluded hepatic veins. RESULTS: IVC stents were successfully placed in 79 of 83 patients, with a success rate of 95%. After the procedure, the symptoms and signs of IVC obstruction disappeared or markedly improved in all patients, and the blockage of hepatic outflow was alleviated in 67 patients. Pericardial effusion, complete atrial ventricular block, and stent migration into the right atrium occurred, respectively, in one patient. During 1-46-month follow-up, stent restenosis occurred in one patient; the other stents remained open and functioned effectively. CONCLUSION: Because of the absence of nonionizing radiation and iodinated contrast material, and its low cost, US is well suited and often preferred for guidance of IVC stent placement.

Adolescent↗
PubMed1999

Characteristics of copper corrosion in simulated uterine fluid in the presence of protein.

In order to acquire more knowledge of the performance of copper-bearing intrauterine devices (Cu-IUDs), corrosion behavior of copper in a simulated uterine fluid was investigated in the presence of proteins. The proteins studied included serum albumin, gamma-globulin and hemoglobin. Electrochemical polarization resistance measurements indicated that, in all cases under study, the corrosion rate of copper declined with time and the proteins always increased the rate. Moreover, different kinds of protein showed different dependence of copper corrosion rate on protein level. Addition of serum albumin initially raised the copper corrosion rate; however, the higher albumin concentration resulted in less promotion of the corrosion. X-ray diffraction (XRD) of the specimen surface showed that, both in the presence and absence of serum albumin, cuprous oxide was the only corrosion product, even though at higher concentrations of albumin less cuprous oxide was formed. This implies that serum albumin does not alter the corrosion mechanism. Electrochemical cathodic reduction of the oxide film and chemical analysis of solution after corrosion testing proved that the proportion of soluble ionic copper in the whole corrosion products varied with the albumin level. The copper corrosion rate in the presence of gamma-globulin or hemoglobin increased monotonically with increasing concentration of the protein. These three proteins shifted the corrosion potential of copper towards negative. It could be inferred that the proteins accelerated the anodic dissolution process of copper and hence enhanced its corrosion.

Body Fluids↗
PubMed1999

Body distribution of camptothecin solid lipid nanoparticles after oral administration.

PURPOSE: The aim of this study was to investigate the specific changes in body distribution of camptothecin (CA) through incorporation into solid lipid nanoparticles (SLN) by peroral route. METHODS: Camptothecin loaded solid lipid nanoparticles (CA-SLN) coated with poloxamer 188 were produced by high pressure homogenization. The CA-SLN were characterized by transmission electron microscopy and electrophoretic mobility measurement. In vitro release characteristics of camptothecin from CA-SLN were studied at different pH media. The concentration of camptothecin in organs was determined using reversed-phase high-performance liquid chromatography with a fluorescence detector after oral administration of CA-SLN and a camptothecin control solution (CA-SOL). RESULTS: Our results showed that CA-SLN had an average diameter 196.8 nm with Zeta potential of -69.3 mV. The encapsulation efficiency of camptothecin was 99.6%, and in vitro drug release was achieved up to a week. There were two peaks in the camptothecin concentration-time curves in plasma and tested organs after oral administration of CA-SLN. The first peak was the result of free drug and the second peak was indicative of gut uptake of CA-SLN after 3 hours. In tested organs, the area under curve (AUC) and mean residence time (MRT) of CA-SLN increased significantly as compared with CA-SOL, and the increase of brain AUC was the highest among all tested organs. CONCLUSIONS: The results indicate SLN could be a promising sustained release and targeting system for camptothecin or other lipophilic antitumor drugs after oral administration.

Administration, Oral↗
PubMed1999

An approach for predicting heterosis based on an additive, dominance and additive x additive model with environment interaction.

A method is proposed for predicting potential heterosis of offspring of crop hybrids by an additive, dominance and additive x additive model (ADAA). By using unbiased predictors of additive and dominance, as well as additive x additive effects, general formulae for predicting heterosis over mid-parent and heterosis over the better parent are derived for different generations. When there exists genotype by environment (GE) interaction, formulae are also derived for predicting interaction heterosis. Heterosis in a specific environment is the sum of heterosis arising from the main genotypic effect and that arising from GE interaction deviation. The epistasis heterosis (DeltaAA) could play an important role in the use of heterosis for both an F1 hybrid and its later generations. In addition, a simple formula is given for predicting the number of generations of a cross that would still keep a certain level of heterosis over the better parent. Data from a diallel cross of cotton are analysed as a worked example for predicting genotypic value, heterosis, and the number of generations for each cross when heterosis over the better parent is larger than 5%.

Environment↗