Biomedical subjects

Z Luo

Publications and source records attributed to Z Luo.

At least 37 records · Page 2Linked to original sources

PubMed2001

Effect of multiple mutations in the core promoter and pre-core/core region of hepatitis B virus genome on the response to interferon in e antigen-positive chronic hepatitis B.

BACKGROUND AND AIMS: Hepatitis B virus (HBV) genomic mutations may be one of the factors that influence the efficacy of interferon (IFN) therapy. The aim of this study was to investigate the effects of mutations in different parts of the HBV genome on IFN therapy. METHODS: We studied the baseline clinical, biochemical, serologic and virologic parameters in 17 patients with e antigen-positive chronic hepatitis B. The DNA sequence of the X gene and pre-core/core gene in serum samples of these patients was analyzed before the initiation of IFN therapy. RESULTS: All five patients with the T1762-A1764 mutation were IFN responsive, while among the 12 remaining patients, only two responded to therapy. Among five patients with both a pre-core A1896 mutation and a mutation in the epitope aa 107-118 of the core region, four were non-responders whereas the fifth responded to therapy. In three other patients with A1896 mutations, one with simultaneous mutations in five lymphocytic epitopes did not respond to therapy; the two remaining patients with concomitant mutations in one or two epitopes were responsive. Serum HBV-DNA levels were lower and titers of antibody to hepatitis B virus core antigen-immunoglobin M (anti-HBc-IgM) were higher in the responders than in the non-responders. Hepatitis B virus genotypes B and C were found to be in all these Chinese patients. CONCLUSIONS: These results suggest that HBV genomic mutations, serum viral loads and titers of anti-HBc-IgM might be predictive of the efficacy of IFN therapy. These clinical findings should be further investigated by in vivo and in vitro experiments.

Adult↗

PubMed2001

Spatio-temporal EEG power spectral patterns during a short daytime nap.

This is an approach to investigate topographic changes in electroencephalographic (EEG) spectral power during pre- and post-nap wakefulness as well as stages 1 (S1) and 2 (S2) NREM sleep in 12 subjects. Delta- and theta-band power significantly increased in the frontal and central regions during S1 and S2 with an increase in inter- and intra-hemispheric correlations. Beta-band power significantly increased in the frontal, central and parietal regions during S2 with an increase in interhemispheric correlation. In contrast, alpha-band power significantly decreased in the parietal-occipital regions during S1 and S2 with a decrease in interhemispheric correlation. Thus, daytime nap modulated spatio-temporal patterns of EEG power spectral patterns in wide scalp regions.

Adult↗

PubMed2001

Extracellular ATP stimulates an inhibitory pathway towards growth factor-induced cRaf-1 and MEKK activation in astrocyte cultures.

ATP, acting via P2Y, G protein-coupled receptors (GPCRs), is a mitogenic signal and also synergistically enhances fibroblast growth factor-2 (FGF-2)-induced proliferation in astrocytes. Here, we have examined the effects of ATP and FGF-2 cotreatment on the main components of the extracellular-signal regulated protein kinase (ERK) cascade, cRaf-1, MAPK/ERK kinase (MEK) and ERK, key regulators of cellular proliferation. Surprisingly, ATP inhibited activation of cRaf-1 by FGF-2 in primary cultures of rat cortical astrocytes. The inhibitory effect did not diminish MEK and ERK activation; indeed, cotreatment resulted in a greater initial activation of ERK. ATP inhibition of cRaf-1 activation was not mediated by an increase in cyclic AMP levels or by protein kinase C activation. ATP also inhibited the activation of cRaf-1 by other growth factors, epidermal growth factor and platelet-derived growth factor, as well as other MEK1 activators stimulated by FGF-2, MEK kinase 1 (MEKK1) and MEKK2. Serotonin, an agonist of another GPCR coupled to ERK, did not inhibit FGF-2-induced cRaf-1 activation, thereby indicating specificity in the ATP-induced inhibitory cross-talk. These findings suggest that ATP stimulates an inhibitory activity that lays upstream of MEK activators and inhibits growth factor-induced activation of cRaf-1 and MEKKS: Such a mechanism might serve to integrate the actions of receptor tyrosine kinases and P2Y-GPCRS:

Adenosine Triphosphate↗

PubMed2001

Regulation of flavin-containing monooxygenase 1 expression by ying yang 1 and hepatic nuclear factors 1 and 4.

The flavin-containing monooxygenases (FMOs) are important for the oxidation of a variety of environmental toxicants, natural products, and therapeutics. Consisting of six family members (FMO1-5), these enzymes exhibit distinct but broad and overlapping substrate specificity and are expressed in a highly tissue- and species-selective manner. Corresponding to previously identified regulatory domains, a YY1 binding site was identified at the major rabbit FMO1 promoter, position -8 to -2, two overlapping HNF1alpha sites, position -132 to -105, and two HNF4alpha sites, position -467 to -454 and -195 to -182. Cotransfection studies with HNF1alpha and HNF4alpha expression vectors demonstrated a major role for each of these factors in enhancing FMO1 promoter activity. In contrast, YY1 was shown by site-directed mutagenesis to be dispensable for basal promoter activity but suppressed the ability of the upstream domains to enhance transcription. Finally, comparisons between rabbit and human FMO1 demonstrated conservation of each of these regulatory elements. With the exception of the most distal HNF4alpha site, each of the orthologous human sequences also was able to compete with rabbit FMO1 cis-elements for specific protein binding. These data are consistent with these same elements being important for regulating human FMO1 developmental- and tissue-specific expression.

Animals↗

PubMed2001

Inhibition of insulin signaling and glycogen synthesis by phorbol dibutyrate in rat skeletal muscle.

Numerous studies have shown a correlation between changes in protein kinase C (PKC) distribution and/or activity and insulin resistance in skeletal muscle. To investigate which PKC isoforms might be involved and how they affect insulin action and signaling, studies were carried out in rat soleus muscle incubated with phorbol esters. Muscles preincubated for 1 h with 1 microM phorbol 12,13-dibutyrate (PDBu) showed an impaired ability of insulin to stimulate glucose incorporation into glycogen and a translocation of PKC-alpha, -betaI, -theta, and -epsilon, and probably -betaII, from the cytosol to membranes. Preincubation with 1 microM PDBu decreased activation of the insulin receptor tyrosine kinase by insulin and to an even greater extent the phosphorylation of Akt/protein kinase B and glycogen synthase kinase-3. However, it failed to diminish the activation of phosphatidylinositol 3'-kinase by insulin. Despite these changes in signaling, the stimulation by insulin of glucose transport (2-deoxyglucose uptake) and glucose incorporation into lipid and oxidation to CO2 was unaffected. The results indicate that preincubation of skeletal muscle with phorbol ester leads to a translocation of multiple conventional and novel PKC isoforms and to an impairment of several, but not all, events in the insulin-signaling cascade. They also demonstrate that these changes are associated with an inhibition of insulin-stimulated glycogen synthesis but that, at the concentration of PDBu used here, glucose transport, its incorporation into lipid, and its oxidation to CO2 are unaffected.

Animals↗

PubMed2001

Ras activation of the Raf kinase: tyrosine kinase recruitment of the MAP kinase cascade.

A continuing focus of our work has been an effort to understand the signal transduction pathways through which insulin achieves its cellular actions. In the mid-1970s, we and others observed that insulin promoted an increase in Ser/Thr phosphorylation of a subset of cellular proteins. This finding was unanticipated, inasmuch as nearly all of the actions of insulin then known appeared to result from protein dephosphorylation. In fact, nearly 15 years elapsed before any physiologic response to insulin attributable to stimulated (Ser/Thr) phosphorylation was established. Nevertheless, based on the hypothesis that insulin-stimulated Ser/Thr phosphorylation reflected the activation of protein (Ser/Thr) kinases downstream of the insulin receptor, we sought to detect and purify these putative, insulin-responsive protein (Ser/Thr) kinases. Our effort was based on the presumption that an understanding of the mechanism for their activation would provide an entry into the biochemical reactions through which the insulin receptor activated its downstream effectors. To a degree that, in retrospect, is surprising, this goal was accomplished, much in the way originally envisioned. It is now well known that receptor tyrosine kinases (RTKs) recruit a large network of protein (Ser/Thr) kinases to execute their cellular programs. The first of these insulin-activated protein kinase networks to be fully elucidated was the Ras-Raf-mitogen-activated protein kinase (MAPK) cascade. This pathway is a central effector of cellular differentiation in development; moreover, its inappropriate and continuous activation provides a potent promitogenic force and is a very common occurrence in human cancers. Conversely, this pathway contributes minimally, if at all, to insulin's program of metabolic regulation. Nevertheless, the importance of the Ras-MAPK pathway in metazoan biology and human malignancies has impelled us to an ongoing analysis of the functions and regulation of Ras and Raf. This chapter will summarize briefly the way in which work from this and other laboratories on insulin signaling led to the discovery of the mammalian MAP kinase cascade and, in turn, to the identification of unique role of the Raf kinases in RTK activation of this protein (Ser/Thr) kinase cascade. We will then review in more detail current understanding of the biochemical mechanism through which the Ras proto-oncogene, in collaboration with the 14-3-3 protein and other protein kinases, initiates activation of the Raf kinase.

14-3-3 Proteins↗

PubMed2001

Molecular regulation of genes encoding xenobiotic-metabolizing enzymes: mechanisms involving endogenous factors.

It is widely recognized that xenobiotic-metabolizing enzymes play a fundamental role in the basic processes of carcinogenesis and toxicity on one hand, and chemoprevention and drug efficacy on the other. Realization that different factors can profoundly affect the expression of these enzymes at the genome level has resulted in an enhanced appreciation of the importance these genes play in our modern industrialized age. There continues to be rapid proliferation of studies addressing the molecular regulation of these genes. The discovery of common signal transduction pathways and transcription factors that dictate tissue and developmental-specific expression, as well as variation in expression within a given tissue, suggest that there may be significant interaction among these various regulatory systems. This report is a summary of a symposium that was part of the Structure, Function and Regulation of Cytochromes P450 and Xenobiotic Metabolizing Enzymes satellite meeting of the 2000 joint meeting of the American Society for Biochemistry and Molecular Biology, the American Society for Pharmacology and Experimental Therapeutics, the French Pharmacological Society, and the Pharmacological Society of Canada held in Boston, Massachusetts. This symposium brought together several speakers who addressed specific receptor-mediated signal transduction pathways involved in the regulation of xenobiotic-metabolizing enzymes, as well as other molecular mechanisms whereby endogenous factors are involved in controlling tissue- and developmental-specific expression.

Enzymes↗

PubMed2001

[Significance of detection of transfusion transmitted virus in extrahepatic tissues].

OBJECTIVE: To investigate the location and distribution of transfusion transmitted virus (TTV) in the liver and extrahepatic tissues. METHODS: TTV DNA was detected in paraffin-embedded autopsy liver and extrahepatic tissues, including liver, pancreas, kidney, spleen, testicle, and heart from 13 patients with non A-G hepatitis by nested-PCR and in situ hybridization (ISH) techniques. RESULTS: Positive hybridization signals of TTV nucleus acid were observed in 5 liver, 3 kidney, 2 pancreas and spleen tissues, respectively. TTV DNA was detected in one from each two samples of testicle and heart. Positive signal was mainly located in nucleoli of the liver and extrahepatic parenchymal cells. There was not obvious pathological damage in those extrahepatic tissues. The positive rate of PCR approximately corresponded to ISH. CONCLUSIONS: TTV can infect hepatic and extrahepatic tissues and its infection in extrahepatic tissues might be responsible for a state of reinfection and higher prevalence in different population.

Adult↗

PubMed2001

Histopathological changes of Macaca mulatta infected with Plasmodium knowlesi.

OBJECTIVE: To study the histopathological changes of relevant internal organs of Macaca mulatta infected with Plasmodium knowlesi (P. knowlesi). METHODS: Histopathological examination of 3 monkeys who died of P. knowlesi infection, 2 P. knowlesi infected monkeys who died of treatment failure with artesunate suppository and 1 P. knowlesi infected monkey that was cured by piperaquine phosphate (PQP) but died of trauma and necrosis of the fore limb. RESULTS: The heart, liver, spleen, lung, kidney, brain, pancreas, parathyroid, pituitary and lymph nodes showed severe pathological changes in 3 monkeys (No. 1, 7 and 12) who died of P. knowlesi infection and 1 infected monkey (No. 72) who died of treatment failure with artesunate suppository. Red blood cells containing malarial parasites and pigments were concentrated in the capillaries of these organs. Malarial pigments were deposited in many organs or phagocytized by macrophages in 1 monkey (No. 131), it was cured by piperaquine phosphate but died of trauma and necrosis of the fore limb; cellular atrophy and disappearance of pancreatic islets, parathyroid and pituitary cells were also observed. One monkey (No. 33) treated with artesunate suppository, showed that blood parasites became negative but recrudesced and pituitary later died from a gavage accident. Its organs showed a significant difference to those of the infected monkeys receiving no treatment. Only the liver Kupffer cells and cerebral matrix contained malarial parasites and pigments; many relevant internal organs showed repair. CONCLUSION: The pathological changes of relevant internal organs of Macaca mulatta infected with P. knowlesi were examined in detail, especially cellular atrophy and the disappearance of pancreatic islets, parathyroid and pituitary cells and myolysis of cardiac muscles. These changes have not previously been reported elsewhere.

Animals↗

PubMed2001

[Morphological observation of Mahaim's fibers in 7 cases].

OBJECTIVE: To investigate the Mahaim's fibers of the cardiac conduction system (CCS) of human hearts and study their morphological features. METHODS: The CCS from 165 cases of sudden death without extracardiac causes and those from 760 cases of non-cardiac death were sampled using a method established by the authors. Serial sections were prepared for histological observation. RESULTS: Mahaim's fibers were discovered in 7 cases, 5 cases were in the sudden death group, accounting for 3% in that group, 2 cases were in the non-cardiac death group, accounting for 0.26% in that group. All cases belonged to the bundle-ventricular branch type. The characteristics of Mahaim's fibers were found to be as follows. Their transverse diameter was 10 - 35 microns. The bodies of the Mahaim's fibers that originated from A-V bundle were slender with nucleus in the middle of the cell. While the shape of cells from the left bundle branch varied according to the origin of the Mahaim's fiber with size enlarging from up downward. Both types of cells showed abundant lightly stained cytoplasm, similar to A-V bundle and left bundle branch cells. The cells were not bifurcated and some of them were surrounded by a thin layer of fibrous tissue. CONCLUSION: Mahaim's fibers are not a rarity and it is an abnormal development of an A-V by-path.

Adolescent↗

PubMed2001

[Microsatellite instability and loss of heterozygosity in squamous cell carcinoma of the head and neck].

OBJECTIVE: To identify the frequency of loss of heterozygosity (LOH) and microsatellite instability (MI) in Chinese sample of squamous cell carcinoma of the head and neck (SCCHN). METHODS: 18 microsatellite markers were selected and used in the analysis of 30 paired SCCHN for LOH and MI by polymerase chain reaction. RESULTS: In 30 cases of SCCHN, LOH was identified in 12 cases (40%) with at least 1 marker. The prevalence rate of LOH was 0 to 21%, much lower than those reported for most markers. 7 out of the 18 markers (D7S480, D7S522, D9S162, D9S168, D9S304, D9S171 and D17S520) were identified as significant (P < 0.05). However there was no statistically significant correlation between the LOH at these loci and the clinical parameters such as pathological types, tumor size and lymph-node metastasis. MI occurred in only 4 patients, but no MI could be observed using the common criteria for defining MI in two or more markers. CONCLUSION: The most common LOH at D7S480, D7S522, D9S162, D9S168, D9S304, D9S171 and D17S520 might imply the existence of potential tumor suppressor gene of a subset of SCCHN, while MI might not be a crucial event.

Adolescent↗

PubMed2001

[Comparison of the effect of fluoride and non-fluoride dentifrices on enamel demineralization and remineralization in vitro].

OBJECTIVE: The purpose of the experiment is to investigate the effect of fluoride dentifrices in China on the intact and artificial caries-like bovine enamels. METHODS: The artificial caries-like lesions were created by dipping the teeth into an acid buffered solution. Both the bovine intact enamels and the artificial caries-like enamels were assigned tooth brushing 20 times every half an hour with 3 kinds of fluoride dentifrices and one kind of non-fluoride dentifrices respectively. The amount of calcium dissolved by lactic acid was determined as the susceptibility of demineralization by atomic adsorption spectrometry (AAS). RESULTS: The group treated with fluoride dentifrice showed significantly less demineralization than the non-fluoride group (P < 0.02). The effect of inhibition of acid solubility in artificial caries-like enamel after tooth brushing is significantly greater than that in intact enamel. CONCLUSION: Fluoride dentifrices in this experiment can prevent both intact enamel and artificial caries-like enamel from acid solubility after tooth brushing, and it seems that the effect of the fluoride dentifrices on the redemineralization is greater than the reduction of enamel solubility.

Animals↗

PubMed2001

[Studies on calluses induced from various explants of Cistanche deserticola].

Calluses were induced from various explants (flower, stem, bud and squama) of Cistanche deserticola Y.C.Ma and compared with each other. The result showed that the inducement rate of ovary and stem were higher than that of other explants which the inducement time was short and the characters of calluses were good. The effect of basal culture medium added hormone on callus reproduction was also studied. The result showed that B5 culture medium added 1 mg/L IBA and 2 mg/L 6-BA was optimal.

Cistanche↗

PubMed2001

[Spectrophotometric study on the interaction of protein with acid dye].

Spectrophotometric characters of protein interaction with chromazurol S(CAS), bromocresol green (BCG), bromopyrogallol red (BPR) and methylthymol blue (MTB) have been studied in acid and alkaline medium respectively. Protein can combine the above mentioned dye to reduce absorptivity of dye solution of CAS and BCG at pH 3.8 and pH 4.0, to add absorptivity of dye solution of BPR and MTB at pH 3.8 and pH 10.8 for the bathochromic shift of wave length of maximal absorption of them to add 10 nm and 20 nm respectively. The linear relationship holds between the reduced or added absorptivity of dye and the optimum concentration range of protein. The interaction mechanism of protein and dye has been discussed tentatively.

Acids↗

PubMed2000

Separation of "light fluorous" reagents and catalysts by fluorous solid-phase extraction: synthesis and study of a family of triarylphosphines bearing linear and branched fluorous tags.

Practical syntheses of new triarylphosphines bearing both linear and branched fluorous tags (Rf) are reported. The phosphines have one, two, or all three aryl rings bearing fluorous tags: (Ph)(3)(-)(n)()P(C(6)H(4)(CH(2))(m)()Rf)(n)(). Fluorous-organic partition coefficients have been measured and the retention properties of both the phosphines and the derived phosphine oxides on fluorous reverse phase silica have been studied. While applications relying on liquid-liquid extractive separations of these phosphines may be limited to those bearing three fluorous chains, the technique of solid phase extraction should be broadly applicable to phosphines, phosphine oxides, and derived metal complexes. A parallel platinum-catalyzed allylation of aldehydes with fluorous allyl stannanes illustrates the usefulness of the new fluorous ligands in small-scale synthesis.

Catalysis↗

PubMed2000

Genetic diversity of hantaviruses isolated in china and characterization of novel hantaviruses isolated from Niviventer confucianus and Rattus rattus.

The antigenic and genetic properties of 46 hantaviruses from China, 13 from patients, 23 from rodents, and 10 from unknown hosts, were compared with those of other hantaviruses. The viruses were classified as either Hantaan (HTN) or Seoul (SEO) viruses. A phylogenetic analysis of the partial M (300 bp) and S (around 485 bp) genomes of HTN viruses identified nine distinct genetic subtypes, one consisting of isolates from Korea. The SEO viruses were divided into five genetic subtypes, although they had less variability than the HTN subtypes. There was a correlation between the subtype and province of origin for four subtypes of HTN viruses, confirming geographical clustering. Hantaan virus NC167 isolated from Niviventer confucianus and SEO virus Gou3 isolated from Rattus rattus were the basal clades in each virus. The phylogenetic trees constructed from the entire S and M segments suggested that NC167 was introduced to N. confucianus in a host-switching event. The reactivity of a panel of 35 monoclonal antibodies was almost exactly the same in NC167 and a representative HTN virus and in Gou3 and a representative SEO virus. However, there was a one-way cross-neutralization between them. These results confirm the varied nature of Murinae-associated hantaviruses in China.

Animals↗

PubMed2000

Structure-function study and anti-HIV activity of synthetic peptide analogues derived from viral chemokine vMIP-II.

The viral macrophage inflammatory protein II (vMIP-II) shows a broad spectrum interaction with both CC and CXC chemokine receptors including CCR5 and CXCR4, two principal coreceptors for the cellular entry of human immunodeficiency virus type 1 (HIV-1). Recently, we have shown that a synthetic peptide derived from the N-terminus of vMIP-II, designated as V1, is a potent antagonist of CXCR4 but not CCR5 [Zhou, N., et al. (2000) Biochemistry 39, 3782-3787]. In this study, we synthesized a series of new peptides derived from other regions of vMIP-II and characterized their binding activities with both CXCR4 and CCR5. The results provided further support for the notion that the N-terminus of vMIP-II is the major determinant for CXCR4 recognition and that vMIP-II probably interacts with other chemokine receptors such as CCR5 with different sequence and conformational determinants. To understand the structure-function relationship of V1 peptide, its solution conformation was studied using circular dichroism spectroscopy, which showed a random conformation similar to that of the corresponding N-terminus in native vMIP-II. In addition, we synthesized a series of mutant analogues of V1 containing alanine, glycine, or phenylalanine substitution at various positions. Residues Val-1, Arg-7, and Lys-9 of V1 peptide were found to be critical for receptor interaction, because single alanine replacement at these positions dramatically decreased peptide binding to CXCR4. In contrast, alanine or phenylalanine substitution at Cys-11 led to significant enhancement in peptide affinity for CXCR4. Finally, we showed that V1 peptide inhibits HIV-1 replication in CXCR4(+) T-cell lines. These studies provide new insights into the structure-function relationship of V1 peptide and demonstrate that this peptide may be a lead for the development of therapeutic agents.

Alanine↗

PubMed2000

Raf-1/MEK/MAPK pathway is necessary for the G2/M transition induced by nocodazole.

The dynamic balance between polymerization and depolymerization of microtubules is critical for cells to enter and exit mitosis, and drugs that disrupt this balance, such as taxol, colchicine, and nocodazole, arrest the cell cycle in mitosis. Although the Raf/MEK/MAPK pathway can be activated by these drugs, its role in mitosis has not been addressed. Here, we characterize activation of Raf/MEK/MAPK by nocodazole when mitosis is induced. We find that at early time points (up to 3 h) in nocodazole induction, Raf/MEK/MAPK is activated, and inhibition of MAPK activation by a MEK inhibitor, PD98059 or U0126, reduces the number of cells entering mitosis by creating a block at G(2). At later time points and in mitosis, activation of MEK/MAPK is severely inhibited, even though Raf-1 activity remains high and can be further increased by growth factor. This inhibition is reversed when cells are released from metaphase and enter G(0)/G(1) phase. In addition, we find that binding of Raf-1 to 14-3-3 is progressively induced by nocodazole, reaching a maximum in mitosis, and that this binding is necessary to maintain mitotic Raf-1 activity. Our present study indicates that activation of the Raf/MEK/MAPK pathway is necessary for the G(2)/M progression.

14-3-3 Proteins↗