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Biomedical subjects

L Tao

Publications and source records attributed to L Tao.

At least 55 records · Page 3Linked to original sources
PubMed2000

Hypomethylation and overexpression of c-jun and c-myc protooncogenes and increased DNA methyltransferase activity in dichloroacetic and trichloroacetic acid-promoted mouse liver tumors.

Dichloroacetic acid (DCA) and trichloroacetic acid (TCA) are mouse liver carcinogens. Methylation of the c-jun and c-myc genes, expression of both genes and DNA methyltransferase (DNA MTase) activity were determined in liver tumors initiated by N-methyl-N-nitrosourea and promoted by DCA and TCA in female B6C3F1 mice. Hypomethylated and over-expression of c-jun and c-myc genes were found in DCA- and TCA-promoted liver tumors. DNA MTase activity was increased in tumors while decreased in non-involved liver. Thus, DCA- and TCA-promoted carcinogenesis appears to include decreased methylation and increased expression of c-jun and c-myc genes in the presence of increased DNA MTase activity.

Alkylating Agents↗
PubMed2000

Light scattering in brain slices measured with a photon counting fiber optic system.

Measurements of intrinsic optical signals (IOSs) from neural tissue, commonly with a reflection-type or transmittance-type set-up, have been used increasingly to study physiological events. Even for the same event, however, such as spreading depression (SD) or osmotic challenge, signals of opposite polarities (increase or decrease) have been obtained by different investigators using similar set-ups under similar conditions. The origin of the inconsistencies is still unknown. It is suggested here that the inconsistencies may be caused by artifacts associated with tissue surface scattering. The main goal of this paper was to present a photon counting fiber optic (PCFO) system designed to exclude surface artifacts and predominantly measure the light scattering (LS) within the tissue. Experiments on rat neocortical slices under osmotic challenges demonstrated the consistency of the PCFO data: hypertonic challenge always increased LS signal while hypotonic challenge decreased it, as long as the challenge did not induce SD. Under strong osmotic challenge (-100 mOsm), the signal suddenly reversed the polarity at the onset of SD induced by the challenge and continued to increase until the challenge was removed. When SD was blocked by high [Mg(2+)](o), the LS signal remained decreased during the -100 mOsm challenge. A spectroscopic study with the PCFO system showed that the spectrum of tissue scattering was almost a flat function in most of the visible range (650-470 nm) with a maximum at 500 nm and a rapid drop at 450 nm.

Animals↗
PubMed2000

Major DNA replication initiation sites in the c-myc locus in human cells.

DNA replication initiation sites and initiation frequencies over 12. 5 kb of the human c-myc locus, including 4.6 kb of new 5' sequence, were determined based on short nascent DNA abundance measured by competitive polymerase chain reaction using 21 primer sets. In previous measurements, no comparative quantitation of nascent strand abundance was performed, and distinction of major from minor initiation sites was not feasible. Two major initiation sites were identified in this study. One predominant site has been located at approximately 0.5 kb upstream of exon 1 of the c-myc gene, and a second new major site is located in exon 2. The site in exon 2 has not been previously identified. In addition, there are other sites that may act as less frequently used initiation sites, some of which may correspond to sites in previous reports. Furthermore, a comparison of the abundance of DNA replication intermediates over this same region of the c-myc locus between HeLa and normal skin fibroblast (NSF) cells indicated that the relative distribution was very similar, but that nascent strand abundance in HeLa cells was approximately twice that in NSF relative to the abundance at the lamin B2 origin. This increased activity at initiation sites in the c-myc locus may mainly be influenced by regulators at higher levels in transformed cells like HeLa.

Cells, Cultured↗
PubMed2000

Induction of vaginal Lactobacillus phages by the cigarette smoke chemical benzo[a]pyrene diol epoxide.

Because smoking increases a woman's risk of contracting bacterial vaginosis (BV), which is manifested by a reduction of vaginal lactobacilli and an overgrowth of anaerobic bacteria, chemicals contained in cigarette smoke were analyzed in vitro to determine their role in reducing lactobacilli. The result showed that trace amounts of benzo[a]pyrene diol epoxide (BPDE), which can be found in vaginal secretion of women who smoke, significantly increased phage induction in lactobacilli. This finding implies that smoking may reduce vaginal lactobacilli by promoting phage induction.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed2000

Generation of CD8+ T cell-generated suppressor factor and beta-chemokines by targeted iliac lymph node immunization in rhesus monkeys challenged with SHIV-89.6P by the rectal route.

The targeted lymph node (TLN) immunization strategy was investigated in macaques, in order to determine the efficacy in generating secretory, systemic, and cellular immune responses, CD8+ T cell-generated suppressor factors, and beta-chemokines. TLN immunization of the rectal and genital mucosa-associated iliac lymph nodes (TILNs) was compared with axillary TLN immunization (TAxLN) using HIV-1 MN/LAI gp140env and SIV p27gag in alum. Significantly higher immune responses, as well as CD8+ T cell-generated anti-SIV factors and the beta-chemokines RANTES, MIP-1alpha, and MIP-1beta, were elicited by iliac as compared with axillary TLN immunization. The immune responses induced by TLN immunization were examined for their capacity to prevent rectal mucosal infection by the pathogenic dual-tropic SHIV-89.6P. Despite significant secretory, serum, cellular, and beta-chemokine responses, the macaques were infected by SHIV-89.6P. Whether the lack of protection was associated with the antigenic unrelatedness of SHIV-89.6P to the immunizing HIV-1 MN/LAI gp140 or to the virus utilizing CXCR4 to a much greater extent than CCR5, remains to be determined.

Animals↗
PubMed2000

Domain growth in ternary fluids: A level set approach

We analyze phase separation in ternary systems in the asymptotic hydrodynamic regime when the volume fractions and concentrations are constant. The multiphase Navier-Stokes equations are solved using a level set method. A new projection method was developed to treat multiple junctions for systems with more than two phases. It is found that surface tension ratios can alter the growth mechanism of a minority phase in the presence of two majority phases. When the minority phase wets the interface of the majority phases the domain growth rate of all three phases is initially similar to that of a symmetric binary fluid but slows down at later times.

Journal Article↗
PubMed2000

In vitro inhibition of commercial douche products against vaginal microflora.

Recently, vaginal douching has been associated with many health risks in women. The aim of this study was to analyze the effect of commercial douche products against various vaginal microorganisms, including lactobacilli. Seven commercial douches were tested against eight Lactobacillus clinical isolates and three type strains from the American Type Culture Collection. BV-associated bacteria included six strains of five genera: Gardnerella, Mobiluncus, Mycoplasma, Peptostreptococcus, and Ureaplasma. Two isolates of group B Streptococcus, and three species of Candida were also tested. The minimal inhibition concentrations and minimal contact times for these products against vaginal microorganisms were determined in broth cultures. Four antiseptic-containing douche products showed a strong inhibitory effect against all vaginal microorganisms tested with a short contact time (less than 1 min). Three vinegar-containing douche products selectively inhibited vaginal pathogens associated with bacterial vaginosis, group B streptococcal vaginitis, and candidiasis, but not lactobacilli. The antimicrobial effects of the commercial douche products varied among different brands and microbial species tested.

Anti-Infective Agents, Local↗
PubMed2000

BTK mutations in patients with X-linked agammaglobulinemia: lack of correlation between presence of peripheral B lymphocytes and specific mutations.

X-linked agammaglobulinemia (XLA) is a human antibody deficiency that results from mutation of the tyrosine kinase btk. We tested the hypothesis that XLA patients who varied from the classic phenotype of XLA by presence of normal or near normal number of peripheral B lymphocytes would have a set of mutations of BTK that is different from the mutations found in patients without peripheral B lymphocytes. The mutations of BTK we found in two patients with normal numbers of peripheral B lymphocytes have been previously identified in patients without peripheral B lymphocytes. A third patient, without peripheral B cells, was found to express normal levels of wild type btk. Exmination of the mutations of the BTK gene in patients in the BTKbase who were identified as having peripheral B lymphocytes found that these same mutations, or mutations of the same protein domains, were also present in patients identified as lacking peripheral B lymphocytes. Analysis of mutations in BTK has previously led to the conclusion that severity of disease in XLA cannot be predicted from the specific mutation of BTK. The results of this study suggest that whether an XLA patient will develop peripheral B lymphocytes cannot be predicted from the specific mutation of BTK.

Agammaglobulinaemia Tyrosine Kinase↗
PubMed2000

Identification of tumor-suppressor genes using human melanoma cell lines UACC903, UACC903(+6), and SRS3 by comparison of expression profiles.

The development and progression of cancer are believed to be due to multiple genetic alterations resulting in complex changes in expression of many genes. The parental malignant melanoma cell line UACC903 displays anchorage-independent growth, and the chromosome 6-suppressed subline UACC903(+6) displays anchorage-dependent growth. The anchorage-independent revertant cell line SRS3 derived from UACC903(+6) by retroviral transduction resembles the phenotype of UACC903. In this study, we first compared the expression profiles of 3317 genes between these three cell lines in pairs by cDNA microarrays, resulting in identification of genes with known suppressor activities. We then demonstrated connexin 43 (Cx43)-suppressing anchorage-independent growth of UACC903 on overexpression. Of 3317 genes with informative expression detected by cDNA microarray, 321 (9.68%) showed expression changes between at least one pair of the three cell lines. Notably, 12 genes displayed higher levels of expression in UACC903(+6) than in both UACC903 and SRS3, providing candidates for further identification of melanoma-suppressor genes. Genes encoding Cx43 (suppressor activity), monocyte chemotactic protein 1 (suppressor activity), and cysteine proteinase P32alpha (apoptotic activity) were all upregulated in UACC903(+6), in contrast to both UACC903 and SRS3. Transfection of Cx43, encoded on human chromosome 6q21-q23, a region frequently altered in malignant melanoma, resulted in its overexpression and the suppression of anchorage-independent growth of UACC903. Thus, our result proves the principle that the combination of the ability to alter cellular phenotype by successive genetic alterations and the ability to examine the global expression profiles facilitates the identification of tumor suppressor genes. Mol. Carcinog. 28:119-127, 2000.

Base Sequence↗
PubMed2000

Heat shock proteins generate beta-chemokines which function as innate adjuvants enhancing adaptive immunity.

Heat shock proteins (HSP) are widely distributed and highly immunogenic molecules. A novel property reported here is that stimulation with HSP70 of CD8-enriched T cells derived from naive non-human primates caused a dose-dependent increase in concentrations of the beta-chemokines RANTES, macrophage inflammatory protein (MIP)-1alpha or MIP-1beta. However, the concentrations of these beta-chemokines were greatly increased when the CD8 T cells derived from HSP70-immunized non-human primates were stimulated with HSP70. HSP linked to peptides or proteins combined generation of beta-chemokines with an adjuvant function by enhancing specific T cell proliferative responses and IgG and IgA antibodies. The beta-chemokine and adjuvant functions were also elicited by topical mucosal administration of HSP linked to an antigen. We postulate that microbial HSP can stimulate beta-chemokine production which may be responsible for innate adjuvanticity, as was found in cells eluted from normal rectal mucosal tissue, and constitutes a significant component of the mucosal-associated lymphoid system. Furthermore, stimulation of innate immunity may drive adaptive immunity and account for the protective effects of HSP against tumors and viruses.

Adjuvants, Immunologic↗
PubMed2000

Diffusion of molecules in brain extracellular space: theory and experiment.

Volume transmission depends on the migration of informational substances through brain extracellular space (ECS) and almost always involves diffusion; basic concepts of diffusion are outlined from both the microscopic viewpoint based on random walks and the macroscopic viewpoint based on the solution of equations embodying Fick's Laws. In a complex medium like the brain, diffusing molecules are constrained by the local volume fraction of the ECS and tortuosity, a measure of the hindrance imposed by cellular obstacles. Molecules can also experience varying degrees of uptake or clearance. Bulk flow and the extracellular matrix may also play a role. Examples of recent work on diffusion of tetramethylammonium (molecular weight, 74) in brain slices, using iontophoretic application and ion-selective microelectrodes, are reviewed. In slices, the volume fraction is about 20% and tortuosity about 1.6, both similar to values found in the intact brain. Using integrative optical imaging, results obtained with dextrans and albumins up to a molecular weight of 70,000 are summarized, for such large molecules the tortuosity is about 2.3. Experiments using synthetic long-chain PHPMA polymers up to 1,000,000 molecular weight show that these molecules also diffuse in the ECS but with a tortuosity of about 1.6. Studies with osmotic challenge show that volume fraction and tortuosity do not vary together as expected when the size of the ECS changes; a model is presented that explains the osmotic-challenge on the basis of changes in cell shape. Finally, new analytical insights are provided into the complex movement of potassium in the brain.

Animals↗
PubMed2000

Up-regulation of beta-chemokines and down-modulation of CCR5 co-receptors inhibit simian immunodeficiency virus transmission in non-human primates.

A non-cognate mechanism of protection against human immunodeficiency virus-1 (HIV-1) infection involves up-regulation of beta-chemokines, which bind and may down-modulate the CCR5 co-receptors, thereby preventing transmission of M-tropic HIV-1. The objective of this investigation was to evaluate this mechanism in vivo in non-human primates. Rhesus macaques were immunized by a modified targeted lymph nodes (TLN) route with recombinant simian immunodeficiency virus (SIV) glycoprotein 120 (gp120) and p27 in alum, and adsorbed recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) with either interleukin (IL)-2 or IL-4. Immunization induced significant increases in the concentrations of CD8 cell-derived suppressor factor (CD8-SF), regulated on activation normal T cells expressed and secreted (RANTES), macrophage inflammatory protein (MIP)-1alpha and MIP-1beta, and down-modulation of the proportion of cells expressing CCR5 (r = 0.737, P<0.05). The macaques were then challenged with SIVmac 220 by the rectal mucosal route. The plasma SIVmac RNA showed a significant inverse correlation with the CD8-SF or the concentration of the three beta-chemokines (r = 0.831 and 0.824, P<0.01), but a positive correlation between the proportion of CCR5+ cells and SIVmac RNA (r = 0.613, P = 0.05). These results demonstrate for the first time in vivo that immunization up-regulates beta-chemokines, which may down-modulate CCR5 co-receptors, and both functions are significantly correlated with the viral load. Hence, the non-cognate beta-chemokine-CCR5 mechanism should be considered as complementary to specific immunity in vaccination against HIV.

Animals↗
PubMed2000

Oxidative degradation of bilirubin produces vasoactive compounds.

Subarachnoid haemorrhage is often followed by haemolysis and concomitant oxidative stress, and is frequently complicated by pathological vasoconstriction or cerebral vasospasm. It is known that upregulation of haem oxygenase (HO-1) is induced by oxidative stress and results in release of biliverdin and bilirubin (BR), which are scavengers of reactive oxygen species (ROS). Here we report biomimetic studies aimed at modelling pathological conditions leading to oxidative degradation of BR. Oxidative degradation products of BR, formed by reaction with hydrogen peroxide (an ROS model system), demonstrated biological activity by stimulating oxygen consumption and force development in vascular smooth muscle from porcine carotid artery. Analogous biological activity was observed with vasoactive cerebrospinal fluid from subarachnoid haemorrhage patients. Three degradation products of BR were isolated: two were assigned as isomeric monopyrrole (C9H11N2O2) derivatives, 4-methyl-5-oxo-3-vinyl-(1, 5-dihydropyrrol-2-ylidene)acetamide and 3-methyl-5-oxo-4-vinyl-(1, 5-dihydropyrrol-2-ylidene)acetamide and the third was 4-methyl-3-vinylmaleimide (MVM), a previously isolated photodegradation product of biliverdin. Possible mechanisms of oxidative degradation of BR are discussed. Tentative assignment of these structures in the cerebrospinal fluid (CSF) of cerebral vasospasm patients has been made. It is proposed that one or more of the degradation products of biliverdin or bilirubin are involved in complications such as vasospasm and or pathological vasoconstriction associated with haemorrhage.

Bilirubin↗
PubMed2000

Effect of trichloroethylene and its metabolites, dichloroacetic acid and trichloroacetic acid, on the methylation and expression of c-Jun and c-Myc protooncogenes in mouse liver: prevention by methionine.

Trichloroethylene (TCE), dichloroacetic acid (DCA), and trichloroacetic acid (TCA) are environmental contaminants that are carcinogenic in mouse liver. 5-Methylcytosine (5-MeC) in DNA is a mechanism that controls the transcription of mRNA, including the protooncogenes, c-jun and c-myc. We have previously reported that TCE decreased methylation of the c-jun and c-myc genes and increased the level of their mRNAs. Decreased methylation of the protooncogenes could be a result of a deficiency in S-adenosylmethionine (SAM), so that methionine, by increasing the level of SAM, would prevent hypomethylation of the genes. For 5 days, female B6C3F1 mice were administered, daily by oral gavage, either 1000 mg/kg body weight of TCE or 500 mg/kg DCA or TCA. At 30 min after each dose of carcinogen, the mice received, by ip injection, 0-, 30-, 100-, 300-, or 450-mg/kg methionine. Mice were euthanized at 100 min after the last dose of DCA, TCA, or TCE. Decreased methylation in the promoter regions of the c-jun and c-myc genes and increased levels of their mRNA and proteins were found in livers of mice exposed to TCE, DCA, and TCA. Methionine prevented both the decreased methylation and the increased levels of the mRNA and proteins of the two pro-tooncogenes. The prevention by methionine of DCA- TCA-, and TCE-induced DNA hypomethylation supports the hypothesis that these carcinogens act by depleting the availability of SAM. Hence, methionine would prevent DNA hypomethylation by maintaining the level of SAM. Furthermore, the results suggest that the dose of DCA, TCA, or TCE must be sufficient to decrease the level of SAM in order for these carcinogens to be active.

Animals↗
PubMed2000

Effect of trihalomethanes on cell proliferation and DNA methylation in female B6C3F1 mouse liver.

Trihalomethanes (chloroform, bromodichloromethane, chlorodibromomethane, and bromoform) are regulated organic contaminants in chlorinated drinking water. In female B6C3F1 mouse liver, the 4 trihalomethanes have demonstrated carcinogenic activity when administered by oral gavage; however, chloroform was not carcinogenic when administered in drinking water. Female B6C3F1 mice were administered the trihalomethanes for 11 days by gavage at 2 dose levels or in the drinking water at approximately 75% saturation. When administered by gavage, the trihalomethanes were toxic to the liver, increased the liver:body weight (bw) ratio, and increased the proliferating cell nuclear antigen-labeling index (PCNA-LI). Chloroform and bromodichloromethane were the most toxic, and they increased the liver:bw ratio the most, while bromoform and chloroform increased the PCNA-LI the most. When administered in drinking water, the toxicity of the trihalomethanes was similar to their low gavage-dose. Furthermore, only chloroform significantly increased the liver:bw ratio and bromoform and chloroform increased the PCNA-LI. Chloroform and bromodichloromethane decreased the level of 5-methylcytosine in hepatic DNA. Methylation in the promoter region of the c-myc gene was reduced by the trihalomethanes. Chloroform administered by gavage was more efficacious than given in drinking water; the efficacy of the other trihalomethanes did not differ for the 2 routes. Thus, in mouse liver, the trihalomethanes administered by gavage enhanced cell proliferation and decreased the methylation of the c-myc gene, consistent with their carcinogenic activity. Furthermore, the more modest toxicity, enhancement of cell proliferation, and decreased methylation induced by chloroform administered in drinking water correlated with its lack of carcinogenic activity. Hence, the activity of the trihalomethanes was dependent on the rate of delivery, i.e. rapid by oral gavage and more slowly in drinking water.

Animals↗
PubMed2000

Isolation, cultivation, and characterization of Borrelia burgdorferi from rodents and ticks in the Charleston area of South Carolina.

Twenty-eight Borrelia burgdorferi isolates from the Charleston, S.C., area are described. This represents the first report and characterization of the Lyme disease spirochete from that state. The isolates were obtained from December 1994 through December 1995 from the tick Ixodes scapularis, collected from vegetation, and from the rodents Peromyscus gossypinus (cotton mouse), Neotoma floridana (eastern wood rat), and Sigmodon hispidus (cotton rat). All isolates were screened immunologically by indirect immunofluorescence with monoclonal antibodies to B. burgdorferi-specific outer surface protein A (OspA) (antibodies H5332 and H3TS) and B. burgdorferi-specific OspB (antibodies H6831 and H614), a Borrelia (genus)-specific antiflagellin antibody (H9724), Borrelia hermsii-specific antibodies (H9826 and H4825), and two polyclonal antibodies (one to Borrelia species and another to B. burgdorferi). Six of the isolates were analyzed by exposing Western blots to monoclonal antibodies H5332, H3TS, H6831, and H9724. All isolates were also analyzed by PCR with five pairs of primers known to amplify selected DNA target sequences specifically reported to be present in the reference strain, B. burgdorferi B-31. The protein profiles of six of the isolates (two from ticks, one from a cotton mouse, two from wood rats, and one from a cotton rat) also were compared by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. We conclude that the 28 Charleston isolates are B. burgdorferi sensu stricto based on their similarities to the B. burgdorferi B-31 reference strain.

Animals↗
PubMed2000

Control of the mode of excitation-contraction coupling by Ca(2+) stores in bovine trachealis muscle.

Full muscarinic stimulation in bovine tracheal smooth muscle caused a sustained contraction and increase in intracellular Ca(2+) concentration ([Ca(2+)](i)) that was largely resistant to inhibition by nifedipine. Depletion of internal Ca(2+) stores with cyclopiazonic acid resulted in an increased efficacy of nifedipine to inhibit this contraction and the associated increase in [Ca(2+)](i). Thus internal Ca(2+) store depletion promoted electromechanical coupling between full muscarinic stimulation and muscle contraction to the detriment of pharmacomechanical coupling. A similar change in coupling mode was induced by ryanodine even when it did not significantly modify the initial transient increase in [Ca(2+)](i) induced by this stimulation, indicating that depletion of internal stores was not necessary to induce the change in excitation-contraction coupling mode. Blockade of the Ca(2+)-activated K(+) channel by tetraethylammonium, charybdotoxin, and iberiotoxin all induced the change in excitation-contraction coupling mode. These results suggest that in this preparation, Ca(2+) released from the ryanodine-sensitive Ca(2+) store, by activating Ca(2+)-activated K(+) channels, plays a central role in determining the expression of the pharmacomechanical coupling mode between muscarinic excitation and the Ca(2+) influx necessary for the maintenance of tone.

Animals↗