Biomedical subjects

L Zheng

Publications and source records attributed to L Zheng.

At least 91 records · Page 5Linked to original sources

PubMed2001

[Application of positron emission tomography in diagnosis and treatment of lung cancer].

OBJECTIVE: To determine the usefulness of positron emission tomography(PET) with fluoro-2-deoxyglucose (FDG-PET) in lung cancer. METHODS: Patients who presented between September 1999 and March 2000 with lung cancer or indeterminate lung lesions on chest CT scan were enrolled and underwent FDG-PET scanning. RESULTS: Of the 88 patients, 68 (77.3%) patients had malignancy and 20(22.7%) patients had a benign lesion. Of the 125 lung lesions, 80(64.0%) malignant lesions had a median standard uptake ratio (SUR) of 2.8(range 0-12.0), while 45(36.0%) benign lesions had a median SUR of 0(range 0-3.7). There was significant difference between the two groups. The diagnostic sensitivity and specificity of PET imaging for lung lesions were associated with the size of lesions but not with radiation or chemotherapy given before. The diagnostic specificity and accuracy of PET for lung lesions were significantly higher than those of CT scan. The sensitivity, specificity and accuracy of SUR method were 65.0%, 91.1% and 74.4% respectively and those of PET visual analysis were 95.0%, 95.6% and 95.2% respectively. The accuracy for lung lesions > or = 1.5 cm with SUR method was higher than that of lesions < 1.5 cm, being 93.8% and 62.3% respectively. The diagnostic sensitivity and accuracy of PET visual analysis for lymph node metastasis were significantly higher than those of CT scan. SUR was not correlated with the degree of cell differentiation, but it decreased significantly in small cell lung cancer after radiation or chemotherapy. CONCLUSIONS: PET is of advantage to the evaluation of lung lesions and diagnosis of lymph node metastasis in lung cancer. PET visual analysis is recommended in lung lesions after radiation or chemotherapy or with size < 1.5 cm in diameter.

Adult↗

PubMed2001

[Immunogenicity and safety of recombinant yeast-derived hepatitis B vaccine (YDV) on adults].

OBJECTIVE: To study the immunogenicity and safety of recombinant yeast-derived hepatitis B vaccine (YDV) on adults. METHODS: One hundred twenty-four healthy teachers of 22 - 58 years old, were randomly selected in Beipiao city, Liaoning province. Their HBsAg, anti-HBs and anti-HBc were all negative and temperature was normal. They were vaccinated with 5 microgram/0.5 ml of YDV, which was made in Beijing Institute of Biologic Products, at 0, 1, 6 months. RESULTS: The positive rates of anti-HBs were 35.0%, 83.3%, 67.2% (P < 0.01) with the mean geometric titre (GMT) of anti-HBs 12.63 mIU/ml, 402.04 mIU/ml and 70.28 mIU/ml (P < 0.01) at 3th, 7th, 12th months respectively. The positive rates of anti-HBs and GMT of anti-HBs became the highest at 7th month, then began to decrease sharply. At 3th, 7th, 12th months the positive rates of anti-HBs and GMT of anti-HBs were higher on female compared to male, but only GMT of anti-HBs was significantly different at 3th month; the positive rates of anti-HBs in below 35 years old group was higher than 35 and over years old group, but it was significantly different only at 12th month. GMT of anti-HBs between the two groups was no obvious difference. Local or systematic addictive reactions were not found in all the subjects in 3 days after injection. CONCLUSION: YDV is effective and safety to adults. The duration of anti-HBs should be further observed.

Adult↗

PubMed2001

[Cloning, sequencing of beagle E-selectin genomic DNA and comparison of it with other species].

OBJECTIVE: Selectins are a group of members of Cell Adhesion Molecular family; they play very important roles in inflammation and neovascularization. The aim of this study is to clone, sequence Beagle E-selectin genomic DNA and make homogeneous analyses to compare it with those of other animals. METHODS: Twelve fragments of genomic DNA of Beagle E-selectin were obtained by PCR, and the 12 fragments were cloned in T-vector. At last, the genomic DNA sequences of Beagle E-selectin were obtained through gene sequencing, assembling and base calling, and the gene structure was analyzed. RESULTS: The sequence of Beagle E-selectin genomic DNA that contained the whole open reading box was acgured. The results of homogeneous analyses showed a great extent of E-selectin gene homology among human, porcine and dog. CONCLUSION: The demonstration of a large extent of the gene homology has substantiated in this connection the important roles of E-selectin in transplantation immunity and neoplasm development.

Animals↗

PubMed2001

Spirochetes--the possible etiological factor of the cheilitis granulomatosa.

OBJECTIVE: To detect spirochetes in sections and to study the therapeutic effect of penicillin in cheilitis granulomatosa (CG) and Melkersson-Rosenthal syndrome (MRS) and the relationship between the spirochetes infection and CG and MRS. METHODS: Routine HE sections and Warthin-Starry special staining were carried out in 20 cases of CG and 6 cases of MRS. Meanwhile there were 9 cases of CG and 2 caes of MRS were treated by penicillin (12 000 000u, i.v., per day) for two courses (14 days). RESULTS: A kind of spirochete was discovered in the sections of all cases of the CG and MRS. The CG and MRS could be divided into two types histopathologically, that is granuloma type and interstitial inflammatory type (non-granuloma type), those morphological changes tallied with spirochetosis. After treatment by penicillin, the facial and labial swelling of the 11 cases of CG and MRS were abated. CONCLUSION: CG and MRS probably are infectious diseases caused by spirochetes.

Anti-Bacterial Agents↗

PubMed2001

[Transmission properties of Faraday anomalous dispersion optical filter at 532 nm].

In this paper the properties of an excited-state potassium Faraday anomalous dispersion optical filter in potassium vapor with a pump wavelength of 769.90 nm (i.e. 4S1/2-->4P1/2 transition) and a signal wavelength of 532 nm (i.e. 4P1/2-->8S1/2 transition) are calculated and discussed. The filter's transmissions versus the laser pump power and the external magnetic-field are obtained. The theoretical results show the transmission characteristics of the filter are relatively insensitive to the laser pump power and magnetic strength. The laser pump powers require range from 0.8 to 6 mW.cm-2. Our model predicts a peak transmission of 50% and an equivalent band-width of 4 GHz for the filter operating on the 4P1/2<--8S1/2 transition in potassium. The optical filter at 532 nm presented in this paper may be used to detect the practical and important frequency-doubled Nd:YAG laser.

English Abstract↗

PubMed2000

Lessons learned from BRCA1 and BRCA2.

BRCA1 and BRCA2 are breast cancer susceptibility genes. Mutations within BRCA1 and BRCA1 are responsible for most familial breast cancer cases. Targeted deletion of Brca1 or Brca2 in mice has revealed an essential function for their encoded products, BRCA1 and BRCA2, in cell proliferation during embryogenesis. Mouse models established from conditional expression of mutant Brca1 alleles develop mammary gland tumors, providing compelling evidence that BRCA1 functions as a breast cancer suppressor. Human cancer cells and mouse cells deficient in BRCA1 or BRCA2 exhibit radiation hypersensitivity and chromosomal abnormalities, thus revealing a potential role for both BRCA1 and BRCA2 in the maintenance of genetic stability through participation in the cellular response to DNA damage. Functional analyses of the BRCA1 and BRCA2 gene products have established their dual participation in transcription regulation and DNA damage repair. Potential insight into the molecular basis for these functions of BRCA1 and BRCA2 has been provided by studies that implicate these two tumor suppressors in both the maintenance of genetic stability and the regulation of cell growth and differentiation.

Animals↗

PubMed2000

Cloning and characterization of human VPS35 and mouse Vps35 and mapping of VPS35 to human chromosome 16q13-q21.

Maintenance of different organelles in eukaryotic cells depends on sorting proteins, which ensure the proper delivery of organelle-specific proteins. The studies on yeast (Saccharomyces cerevisiae) VPS35, a hydrophilic membrane protein having a direct role in the retrieval of cargo proteins, suggest a mechanism underlying a possible lysosomal protein-sorting pathway in mammalian cells. Here, we report the isolation of human and mouse VPS35 cDNAs, which are 3208 and 3186 bp in length, respectively. The deduced proteins of the two cDNAs, which are both composed of 796 amino acids and share 99% identity, show homology to yeast VPS35 and other VPS35 homologues of various sources ranging from Schizosaccharomyces pombe to Drosophila melanogaster (31-56% identity and 49-71% similarity), especially in their amino- and carboxyl-termini. The conservation of VPS35 suggests that the function of this class of protein is important. The results of Northern hybridization of human VPS35 in 16 tissues showed that one transcript of 3.6 kb was highly expressed in brain, heart, testis, ovary, small intestine, spleen, skeletal muscle, and placenta and expressed at moderate or low levels in other tissues. Another transcript of 3.0 kb was also expressed with proportionally lower levels than the 3.6-kb transcript in all the tissues except that the 3.0-kb transcript was not detected in brain. Mouse Vps35 was widely expressed as a 3.4-kb transcript. In addition, human VPS35 was assigned to human chromosome 16q13-q21 by radiation hybrid mapping.

Amino Acid Sequence↗

PubMed2000

The deaf jerker mouse has a mutation in the gene encoding the espin actin-bundling proteins of hair cell stereocilia and lacks espins.

The espins are actin-bundling proteins of brush border microvilli and Sertoli cell-spermatid junctions. We have determined that espins are also present in hair cell stereocilia and have uncovered a connection between the espin gene and jerker, a recessive mutation that causes hair cell degeneration, deafness, and vestibular dysfunction. The espin gene maps to the same region of mouse chromosome 4 as jerker. The tissues of jerker mice do not accumulate espin proteins but contain normal levels of espin mRNAs. The espin gene of jerker mice has a frameshift mutation that affects the espin C-terminal actin-bundling module. These data suggest that jerker mice are, in effect, espin null and that the jerker phenotype results from a mutation in the espin gene.

Amino Acid Sequence↗

PubMed2000

In vivo formation of complex microvessels lined by human endothelial cells in an immunodeficient mouse.

We have identified conditions for forming cultured human umbilical vein endothelial cells (HUVEC) into tubes within a three-dimensional gel that on implantation into immunoincompetent mice undergo remodeling into complex microvessels lined by human endothelium. HUVEC suspended in mixed collagen/fibronectin gels organize into cords with early lumena by 24 h and then apoptose. Twenty-hour constructs, s.c. implanted in immunodeficient mice, display HUVEC-lined thin-walled microvessels within the gel 31 days after implantation. Retroviral-mediated overexpression of a caspase-resistant Bcl-2 protein delays HUVEC apoptosis in vitro for over 7 days. Bcl-2-transduced HUVEC produce an increased density of HUVEC-lined perfused microvessels in vivo compared with untransduced or control-transduced HUVEC. Remarkably, Bcl-2- but not control-transduced HUVEC recruit an ingrowth of perivascular smooth-muscle alpha-actin-expressing mouse cells at 31 days, which organize by 60 days into HUVEC-lined multilayered structures resembling true microvessels. This system provides an in vivo model for dissecting mechanisms of microvascular remodeling by using genetically modified endothelium. Incorporation of such human endothelial-lined microvessels into engineered synthetic skin may improve graft viability, especially in recipients with impaired angiogenesis.

Animals↗

PubMed2000

Cloning and mapping of human PKIB and PKIG, and comparison of tissue expression patterns of three members of the protein kinase inhibitor family, including PKIA.

Two novel members of the human cAMP-dependent protein kinase inhibitor (PKI) gene family, PKIB and PKIG, were cloned. The deduced proteins showed 70% and 90% identity with mouse PKIbeta and PKIgamma respectively. Both the already identified pseudosubstrate site and leucine-rich nuclear export signal motifs were defined from the 11 PKIs of different species. The PKIB and PKIG genes were mapped respectively to chromosome 6q21-22.1, using a radiation hybrid GB4 panel, and to chromosome 20q13.12-13.13, using a Stanford G3 panel. Northern-blot analysis of three PKI isoforms, including the PKIA identified previously, revealed significant differences in their expression patterns. PKIB had two transcripts of 1.9 kb and 1.4 kb. The former transcript was abundant in both placenta and brain and the latter was expressed most abundantly in placenta, highly in brain, heart, liver, pancreas, moderately in kidney, skeletal muscle and colon, and very little in the other eight tissues tested. PKIG was widely expressed as a 1.5-kb transcript with the highest level in heart, hardly detectable in thymus and peripheral blood leucocytes and was moderately expressed in the other tissues, with slightly different levels. However, PKIA was specifically expressed as two transcripts of 3.3 kb and 1.5 kb in heart and skeletal muscle. The distinct expression patterns of the three PKIs suggest that their roles in various tissues are probably different.

Adaptor Proteins, Signal Transducing↗

PubMed2000

Functional link of BRCA1 and ataxia telangiectasia gene product in DNA damage response.

BRCA1 encodes a familial breast cancer suppressor that has a critical role in cellular responses to DNA damage. Mouse cells deficient for Brca1 show genetic instability, defective G2-M checkpoint control and reduced homologous recombination. BRCA1 also directly interacts with proteins of the DNA repair machinery and regulates expression of both the p21 and GADD45 genes. However, it remains unclear how DNA damage signals are transmitted to modulate the repair function of BRCA1. Here we show that the BRCA1-associated protein CtIP becomes hyperphosphorylated and dissociated from BRCA1 upon ionizing radiation. This phosphorylation event requires the protein kinase (ATM) that is mutated in the disease ataxia telangiectasia. ATM phosphorylates CtIP at serine residues 664 and 745, and mutation of these sites to alanine abrogates the dissociation of BRCA1 from CtIP, resulting in persistent repression of BRCA1-dependent induction of GADD45 upon ionizing radiation. We conclude that ATM, by phosphorylating CtIP upon ionizing radiation, may modulate BRCA1-mediated regulation of the DNA damage-response GADD45 gene, thus providing a potential link between ATM deficiency and breast cancer.

Animals↗

PubMed2000

Molecular cloning and mapping of the brain-abundant B1gamma subunit of protein phosphatase 2A, PPP2R2C, to human chromosome 4p16.

Protein phosphatase 2A (PP2A) is one kind of serine/ threonine protein phosphatase regulating mainly cell growth and division. It comprises three subunits, A, B, and C. The B-subunit is involved in enzyme activity and substrate specificity. The B-subunit family is of great diversity and is divided into three classes, the B1, B2, and B3 subfamilies. Until now, two members of the B1 subfamily, B1alpha and B1beta, have been identified in human. In this report, the third member of the sub-family, B1gamma, was identified, and its cDNA was isolated from a human brain cDNA library. This novel cDNA is 4,120 bp in length and contains an open reading frame (nt 55-1,398) encoding 447 amino acid residues. The putative protein shares 81 and 85% identity with B1alpha (PPP2R2A) and B1beta (PPP2R2B), respectively, and was named PPP2R2C for its high level of homology to the other two isoforms. One remarkable characteristic of this novel gene is that it is highly expressed in brain with a 4.7-kb transcript while it is nearly undetectable in other tissues. In addition, the PPP2R2C gene was localized to human chromosome 4p16 between markers D4S2925 and D4S3007 with 5.45 cR (LOD > 14) and 2.63 cR (LOD > 15) RH distance, respectively, by radiation hybrid panel mapping.

Amino Acid Sequence↗

PubMed2000

Distinct Ca2+ binding properties of novel C2 domains of plant phospholipase dalpha and beta.

Of the isoforms of plant phospholipase D (PLD) that have been cloned and characterized, PLDalpha requires millimolar levels of Ca(2+) for optimal activity, whereas PLDbeta is most active at micromolar concentrations of Ca(2+). Multiple amino acid sequence alignments suggest that PLDalpha and PLDbeta both contain a Ca(2+)-dependent phospholipid-binding C2 domain near their N termini. In the present study, we expressed and characterized the putative C2 domains of PLDalpha and PLDbeta, designated PLDalpha C2 and PLDbeta C2, by CD spectroscopy, isothermal titration calorimetry, and phospholipid binding assay. Both PLD C2 domains displayed CD spectra consistent with anticipated major beta-sheet structures but underwent spectral changes upon binding Ca(2+); the magnitude was larger for PLDbeta C2. These conformational changes, not shown by any of the previously characterized C2 domains of animal origin, occurred at micromolar Ca(2+) concentrations for PLDbeta C2 but at millimolar levels of the cation for PLDalpha C2. PLDbeta C2 exhibited three Ca(2+)-binding sites: one with a dissociation constant (K(d)) of 0.8 microm and the other two with a K(d) of 24 micrometer. In contrast, isothermal titration calorimetry data of PLDalpha C2 were consistent with 1-3 low affinity Ca(2+)-binding sites with K(d) in the range of 590-470 micrometer. The thermodynamics of Ca(2+) binding markedly differed for the two C2 domains. Likewise, PLDbeta C2 bound phosphatidylcholine (PC), the substrate of PLD, in the presence of submillimolar Ca(2+) concentrations, whereas PLDalpha C2 did so only in the presence of millimolar levels of the metal ion. Both C2 domains bound phosphatidylinoistol 4,5-bisphosphate, a regulator of PC hydrolysis by PLD. However, added Ca(2+) displaced the bound phosphatidylinoistol 4,5-bisphosphate. Ca(2+) and PC binding properties of PLDalpha C2 and PLDbeta C2 follow a trend similar to the Ca(2+) requirements of the whole enzymes, PLDalpha and PLDbeta, for PC hydrolysis. Taken together, the results suggest that the C2 domains of PLDalpha and PLDbeta have novel structural features and serve as handles by which Ca(2+) differentially regulates the activities of the isoforms.

Amino Acid Sequence↗

PubMed2000

A domain in TNF receptors that mediates ligand-independent receptor assembly and signaling.

A conserved domain in the extracellular region of the 60- and 80-kilodalton tumor necrosis factor receptors (TNFRs) was identified that mediates specific ligand-independent assembly of receptor trimers. This pre-ligand-binding assembly domain (PLAD) is physically distinct from the domain that forms the major contacts with ligand, but is necessary and sufficient for the assembly of TNFR complexes that bind TNF-alpha and mediate signaling. Other members of the TNFR superfamily, including TRAIL receptor 1 and CD40, show similar homotypic association. Thus, TNFRs and related receptors appear to function as preformed complexes rather than as individual receptor subunits that oligomerize after ligand binding.

Amino Acid Substitution↗

PubMed2000

Cytoprotection of human umbilical vein endothelial cells against apoptosis and CTL-mediated lysis provided by caspase-resistant Bcl-2 without alterations in growth or activation responses.

Graft endothelial cells are primary targets of host CTL-mediated injury in acute allograft rejection. As an in vitro trial of gene therapy to reduce CTL-mediated endothelial injury, we stably transduced early passage HUVEC with a caspase-resistant mutant form (D34A) of the anti-apoptotic gene Bcl-2. Bcl-2 transductants were compared with HUVEC transduced in parallel with an enhanced green fluorescent protein (EGFP) gene. Both transduced HUVEC have equivalent growth rates in complete medium and both show contact inhibition of growth. However, compared with EGFP-transduced HUVEC, the Bcl-2-transduced cells are resistant to the apoptotic effects of serum and growth factor withdrawal and are also resistant to the induction of apoptosis by staurosporine or by ceramide, with or without TNF. Transduced Bcl-2 did not reduce TNF-mediated NF-kappaB activation or constitutive expression of class I MHC molecules. HUVEC expressing D34A Bcl-2 were significantly more resistant to lysis by either class I-restricted alloreactive or PHA-redirected CTL than were HUVEC expressing EGFP. We conclude that transduction of graft endothelial cells with D34A Bcl-2 is a possible approach for reducing allograft rejection.

Apoptosis↗

PubMed2000

Clustering of beta(2)-integrins on human neutrophils activates dual signaling pathways to PtdIns 3-kinase.

The beta(2)-integrins on leukocytes can serve as a signaling unit during cell adhesion and locomotion, and to further clarify this important property we investigated the possible mechanisms of beta(2)-integrin-induced activation of PtdIns 3-kinase. It has previously been demonstrated that clustering of beta(2)-integrins activates p21(ras) by a tyrosine kinase-dependent pathway, and here we show that active p21(ras) interacts with its downstream target, PtdIns 3-kinase. Engagement of beta(2)-integrins also activates the tyrosine kinases p58(c-fgr) and p59/61(hck) and causes them to associate with the p85 subunit of PtdIns 3-kinase. These findings suggest a mechanism whereby p58(c-fgr) and p59/61(hck) are directly involved in the activation of PtdIns 3-kinase. No coupling between p58(c-fgr) and p59/61(hck) could be detected; hence these kinases probably trigger independent but parallel signals to PtdIns 3-kinase. The effect of beta(2)-integrin clustering on PtdIns 3-kinase activity was monitored as the activation of protein kinase B (PKB). Stimulation of PKB by beta(2)-integrins was abolished by genistein and wortmannin but not by using methyl transferase inhibitors to abrogate the influence of p21(ras)-related proteins. Thus, even if PtdIns 3-kinase is not activated by p21(ras), it can maintain full enzyme activity due to the mentioned interaction with p58(c-fgr) or p59/61(hck). These tyrosine kinases apparently activate similar pathways that operate in parallel and therefore have the potential to substitute for each other in mediating adhesion and regulating cell locomotion.

Antibodies, Monoclonal↗

PubMed2000

Activation of human neutrophils by Mycobacterium tuberculosis H37Ra involves phospholipase C gamma 2, Shc adapter protein, and p38 mitogen-activated protein kinase.

Recent studies have shown that human neutrophils play a significant protective role in mycobacteria infection. When encountered with mycobacteria, neutrophils exhibit the typical early bactericidal responses including phagocytosis and generation of reactive oxygen intermediates (ROI), but the underlying mechanisms are largely unknown. The present study shows that stimulation of neutrophils with an attenuated strain of Mycobacterium tuberculosis H37Ra (Mtb) led to a tyrosine kinase-dependent ROI production in these cells. Stimulation with Mtb induces a rapid and transient tyrosine phosphorylation of several proteins, one of which was identified as phospholipase C gamma 2 (PLC gamma 2). Several tyrosine-phosphorylated proteins were associated with the PLC gamma 2 precipitates from Mtb-stimulated neutrophils, of which pp46 was characterized as the Shc adapter protein. A role for PLC gamma 2-Shc association in the generation of ROI is supported by the observations that stimulation with Mtb causes the activation of p38 mitogen-activated protein kinase (MAPK), a downstream target of the Shc/Ras signaling cascade, and that the effect of genistein on ROI production coincided with its ability to inhibit both PLC gamma 2-Shc association and p38 MAPK activation. Moreover, pretreatment of neutrophils with a PLC inhibitor markedly suppresses the Mtb-stimulated ROI production as well as p38 MAPK activation in these cells. Taken together, these results indicate that stimulation of neutrophils with Mtb triggers the tyrosine phosphorylation of PLC gamma 2 and its association with Shc, and that such association is critical for the Mtb-stimulated ROI production through activating p38 MAPK.

Calcium↗

PubMed2000

Active MR guidance of interventional devices with target-navigation.

This project incorporated a novel inductive coupling structure of three micro coils into an invasive device tip to determine both its tip position and orientation. Moreover, with the introduction of a new target-navigation technique the MR scan plane was defined automatically by the invasive device orientation and target tissue location. A time domain multiplexing technique was applied for simultaneous MR imaging and device tracking. Using these techniques, the acquired MR images always showed both the invasive device and its target tissue. Thus, roadmap images and their potential misregistration errors were avoided. A graphical user interface (GUI) was also designed to assist interventional physicians in monitoring and guiding the insertion of the interventional device. Ex vivo phantom and in vivo animal experiments were performed to test this new technique. The methods developed in this project provide a new active technique for interventional device guidance using MRI. Magn Reson Med 44:56-65, 2000.

Animals↗