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Biomedical subjects

M Ding

Publications and source records attributed to M Ding.

At least 181 records · Page 10Linked to original sources
PubMed1995

[The infection of hepatitis D virus in adult tupaia].

A new animal model of HDV/HBV infection in adult tupaia (tree shrews) was established to study its pathogenesis and treatment of hepatitis D. In 20 artificially fed adult tupaiae, the positive rate of serum HBsAg was 75% (15/20) after inoculation of human HBV DNA positive serum. After inoculation with positive human serum HBV DNA and positive HDV RNA by way of coinfection and superinfection, serum HBsAg, HDAg and anti-HD were positive one after another in 8 out of 13 tupaiae of the coinfection group and in 6 out of 9 tupaiae of the superinfection group. In some of them HDV RNA was positive in serum or in liver tissue. Transmission of HDV/HBV infection among tupaiae was successful. In group I, animals were inoculated with human HDV/HBV positive serum. In Group II and III, animals were inoculated with tupaia HDV/HBV positive serum of the Group I and II respectively. Serum HBsAg, HDAg and anti-HD became positive one after another in 3 out of 4 tupaiae of the Group II and 4 out 5 tupaiae of the group III. In 2 animals of the Group III, serum HDV RNA was positive and HBsAg and HDAg were detected in the liver tissue. Serum HBsAg was persistantly positive for 16-19 months in the superinfection group. In 2 of them, serum HDAg and anti-HD were alternatively positive and in one of them serum anti-HD was positive persistantly indicating that HDV infection may persist and transform into chronic HDV infection. In the HDV infected tupaiae, there were elevated serum ALT and hepatitis-like pathological changes in the liver tissue which were similar to those in the chimpanzee. We conclude that tupaia may be used as an experimental model of hepatitis D.

Animals↗
PubMed1994

Binding of TFIID to the CYC1 TATA boxes in yeast occurs independently of upstream activating sequences.

Functional transcription initiation complexes can be assembled in vitro without the aid of regulatory factors that bind to upstream activating sequences. However, promoters that lack upstream activating sequences are transcribed poorly if at all in vivo, suggesting that regulatory factors are necessary for the assembly of transcription initiation complexes in cells. To test this possibility, we asked whether the general transcription factor TFIID can bind to a promoter in yeast that lacks upstream activating sequences and is transcriptionally inactive. Analysis of an inactive CYC1 core promoter by high-resolution genomic footprinting revealed efficient binding of TFIID to either of two TATA box elements. Addition of a heat shock element rendered this promoter highly responsive to induction of transcription by heat shock but did not alter the TATA box footprints in the core promoter. Inactivation of all but one TATA box by site-directed mutagenesis did not prevent TFIID from binding to the remaining wild-type TATA box independently of regulatory sequences. These results indicate that upstream regulatory factors are not required for the in vivo binding of TFIID to the CYC1 promoter and that binding of TFIID to DNA is not necessarily a rate-limiting step in the activation of transcription in cells. Differences in chromatin structure may account for why regulatory transcription factors are required for the binding of TFIID to some promoters but not to others.

Base Sequence↗
PubMed1994

The interleukin-1-induced increase of substance P in sympathetic ganglia is not mediated by ciliary neurotrophic factor.

Interleukin-1 (IL-1) induction of substance P (SP) in cultured sympathetic ganglia requires a soluble intermediate molecule that is present in IL-1 conditioned medium (IL-1CM). One of the required intermediates is leukemia inhibitory factor (LIF; Shadiack et al., J Neurosci 13:2601-2609, 1993). In the present study we have examined the possibility that ciliary neurotrophic factor (CNTF) is another intermediate involved in the IL-1 induction of sympathetic SP. CNTF mimics the action of IL-1CM by raising both SP and choline acetyltransferase activity--actions that are blocked by a specific neutralizing antiserum for CNTF. However, IL-1CM and CNTF differ in their response to depolarizing agents: while KCl (40 mM) blocks the action of IL-1CM (and LIF), it enhances the action of CNTF. Furthermore, neither CNTF bioactivity nor CNTF protein is detected in IL-1CM. Neutralizing antiserum to CNTF fails to block the action of either IL-1 or IL-1CM, suggesting that neither a soluble nor a membrane-bound form of the molecule is active in direct response to IL-1 action. While Northern blots confirm the presence of both CNTF and CNTF receptor mRNA in neonatal ganglia, neither culturing nor IL-1 treatment alters these mRNA levels. These data taken together suggest that while CNTF is present and possibly active in sympathetic ganglia, it is not a mediator of the IL-1 induction of SP.

Animals↗
PubMed1994

One-electron reduction of vanadate by ascorbate and related free radical generation at physiological pH.

The one-electron reduction of vanadate (vanadium(V)) by ascorbate and related free radical generation at physiological pH was investigated by ESR and ESR spin trapping. The spin trap used was 5,5-dimethyl-1-pyrroline N-oxide (DMPO). Incubation of vanadium(V) with ascorbate generated significant amounts of vanadium(IV) in phosphate buffer (pH 7.4) but not in sodium cacodylate buffer (pH 7.4) nor in water. The vanadium(IV) yield increased with increasing ascorbate concentration, reaching a maximum at a vanadium(V): ascorbate ratio of 2:1. Addition of formate to the incubation mixture containing vanadium(V), ascorbate, and phosphate generated carboxylate radical (.COO-), indicating the formation of reactive species in the vanadium(V) reduction mechanism. In the presence of H2O2 a mixture of vanadium(V), ascorbate, and phosphate buffer generated hydroxyl radical (.OH) via a Fenton-like reaction (vanadium(IV)+H2O2-->vanadium(V)+.OH+OH-). The .OH yield was favored at relatively low ascorbate concentrations. Omission of phosphate sharply reduced the .OH yield. The vanadium(IV) generated by ascorbate reduction of vanadium(V) in the presence of phosphate was also capable of generating lipid hydroperoxide-derived free radicals from cumene hydroperoxide, a model lipid hydroperoxide. Because of the ubiquitous presence of ascorbate in cellular system at relatively high concentrations, one-electron reduction of vanadium(V) by ascorbate together with phosphate may represent an important vanadium(V) reduction pathway in vivo. The resulting reactive species generated by vanadium(IV) from H2O2 and lipid hydroperoxide via a Fenton-like reaction may play a significant role in the mechanism of vanadium(V)-induced cellular injury.

Ascorbic Acid↗
PubMed1994

Cloning and analysis of MAGE-1-related genes.

The spectrum of MAGE gene expression in the human melanoma cell line DM150 was examined using reverse transcription polymerase chain reaction and cDNA cloning. We have isolated five full-length cDNAs from DM150 which were identified as MAGE-1, MAGE-3, MAGE-12 and two previously undescribed MAGE genes, MAGE-3b and MAGE-X2. DNA sequence analysis of the coding regions of the MAGE-3b and MAGE-X2 genes revealed 83% and 88% identity with MAGE-1, while MAGE-3b was 98% homologous with the full length MAGE-3 clone. The predicted amino acid sequences of MAGE-X2 and MAGE-3b contain consensus HLA-A1 peptide binding motifs, suggesting that, like MAGE-1, they may code for tumor-associated antigens. In addition, a nonamer peptide encoded by both the MAGE-3 and MAGE-12 genes was shown by direct binding studies to contain an aggretope for HLA-A2.

Amino Acid Sequence↗
PubMed1994

Complete primary structure of the sixth chain of human basement membrane collagen, alpha 6(IV). Isolation of the cDNAs for alpha 6(IV) and comparison with five other type IV collagen chains.

Basement membranes were previously believed to contain five distinct type IV collagen subunits. We have recently isolated part of the cDNA for a novel type IV collagen, alpha 6(IV), and shown that COL4A6, the gene encoding this new chain, is deleted in Alport syndrome-associated leiomyomatosis (Zhou, J., Mochizuki, T., Smeets, H., Antignac, C., Laurila, P., de Paepe, A., Tryggvason, K., and Reeders, S. T. (1993) Science 261, 1167-1169). Here, we describe the entire human alpha 6(IV) cDNA and show that the gene encodes a classical type IV collagen with homology throughout its length to all the other five chains. There is a 21-residue signal peptide, a 1417-residue collagenous domain interrupted at 25 points, and a 228-residue carboxyl-terminal non-collagenous domain. When the complete primary structure of this new chain was compared with all the other known chains, it became clear that alpha 6(IV) has the most resemblance to alpha 2(IV) and alpha 4(IV). The evolution of the six chains was deduced, allowing a new classification of the type IV collagen family. The alpha 6(IV) chain is a candidate gene for X-linked Alport syndrome; knowledge of the complete structure of the chain will permit us to screen systematically for mutations in patients and to generate recombinant proteins and synthetic peptides for further study of cell-matrix interactions involving the alpha 6(IV) chain.

Amino Acid Sequence↗
PubMed1994

Early gene changes in myocardial ischemia.

After certain periods of myocardial ischemia and reperfusion, cardiac dysfunction exists in the absence of myonecrosis. In a blood-perfused isolated rat heart model, we have demonstrated early gene changes that are associated with global myocardial "stunning." Early gene changes included elevations in the expression of messenger RNAs for HSP70, c-myc and c-fos. Increased expression of messenger RNAs for protooncogenes is an important observation because of the role of protooncogenes as nuclear transcription factors. From these study findings, it would appear that the stunning state is associated with early gene changes that may signal the induction of a hypertrophic process. Subsequent studies are required to demonstrate the exact events which take place in the course of stunning that directly initiate an alteration in gene expression.

Animals↗
PubMed1994

Effect of triiodothyronine on postischemic myocardial function in the isolated heart.

Thyroid dysfunction has been shown to have a significant impact on hemodynamic status and cardiac function. The purpose of this study was to determine the influence of triiodothyronine (T3) on cardiac functional recovery after ischemia in a dose-dependent manner. Postischemic functional recovery was assessed in isolated rabbit hearts mounted in a modified Langendorff preparation. Left ventricular systolic, diastolic, and peak developed pressures were measured before and after ischemia, and calculated as a percentage of preischemic function. Two cohorts of hearts were studied: the first was exposed to warm ischemia until a myocardial contracture of 4 mmHg was produced; the second cohort was exposed to warm ischemia until a contracture of 15 mm Hg was observed. In each cohort, T3 was added to the perfusion solution after ischemia in a physiologic concentration (2.5 x 10(-9) g/mL; 1 x T3), as well as ten times (2.5 x 10(-8) g/mL; 10 x T3) and a hundred times (2.5 x 10(-7) g/mL; 100 x T3) the physiologic concentration. One group, given the carrier only but without T3, served as the control. Rabbit hearts exposed to a short period of ischemia (4-mmHg diastolic contracture) showed increased recovery with 1 x T3 and 10 x T3. 100 x T3 did not bring about improved left ventricular recovery versus that in the control group. Rabbit hearts in the 15 mm Hg-diastolic contracture cohort showed increased recovery with 10 x T3 but not with 1 x T3. 100 x T3 led to decreased recovery in this cohort versus that in the control group.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Lipopolysaccharide induces substance P in sympathetic ganglia via ganglionic interleukin-1 production.

The immune cytokine interleukin-1 (IL-1) causes a pronounced elevation in substance P (SP) immunoreactivity and the mRNA coding for its preprotachykinin precursor in cultured superior cervical (sympathetic) ganglia (SCG; Jonakait and Schotland, 1990; Freidin and Kessler, 1991; Hart et al., 1991). In this study we have investigated the possibility that the SCG can respond to other immune stimulators, notably lipopolysaccharide (LPS), a product of bacterial cell walls. LPS treatment of cultured SCG resulted in a dose-dependent increase in SP. However, LPS did not induce SP in the absence of non-neuronal cells, suggesting the necessity of a non-neuronal cell-derived intermediate. Since the LPS induction of SP was partially blocked by a specific IL-1 receptor antagonist (IL-1ra) and since LPS induced approximately an 8-fold increase in mRNA coding for IL-1 itself, we concluded that IL-1 is at least one of these LPS-induced intermediates. TNF-alpha, which also raises SP levels, may be another. IL-6, which may also be increased by LPS, does not increase levels of SP. The synthetic glucocorticoid hormone dexamethasone (DEX) blocks the LPS induction of SP with a Ki approximating 8 x 10(-11) M. The inhibition is due in part to the blockade of the LPS induction of ganglionic IL-1 mRNA. Moreover, inhibition of the LPS induction of SP by indomethacin implies mediation of the effect through prostaglandins. The inhibition by indomethacin suggests a non-monocytic cell source since prostaglandins are thought to restrict the LPS induction of monocytic IL-1.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

The nonlinear dynamics of speech categorization.

Little is known about the processes underlying the nonlinear relationship between acoustics and speech perception. In Experiment 1, we explored the effects of systematic variation of a single acoustic parameter (silent gap duration between a natural utterance of s and a synthetic vowel ay) on judgements of speech category. The resulting shifts in category boundary between say and stay showed rich dynamics, including hysteresis, contrast, and critical boundary effects. We propose a dynamical model to account for the observed patterns. Experiment 2 evaluated one prediction of the model, that changing the relative stability of the two percepts allows categorical switching. In agreement with the model; an increase in the number of stimulus repetitions maximized the frequency of judgments of category change near the boundary. Thus, a dynamical approach affords the rudiments for a theory of the effects of temporal context on speech categorization.

Acoustic Stimulation↗
PubMed1994

Reaction of Cr(VI) with ascorbate and hydrogen peroxide generates hydroxyl radicals and causes DNA damage: role of a Cr(IV)-mediated Fenton-like reaction.

Incubation of Cr(VI) with ascorbate generated Cr(V), Cr(IV) and ascorbate-derived carbon-centered alkyl radicals, as well as formyl radicals. H2O2 caused generation of hydroxyl radicals (OH) and much higher levels of Cr(V), showing that .OH can be generated via a Cr(IV)-mediated Fenton-like reaction (Cr(IV) + H2O2-->Cr(V) + .OH + OH-). 1,10-Phenanthroline and deferoxamine inhibited the formation of both .OH and Cr(V) from the reaction of Cr(VI) with ascorbate in the presence of H2O2. Electrophoretic assays showed that ascorbate-derived free radicals caused DNA double-strand breaks. .OH radicals generated by Cr(V)- and Cr(IV)-mediated Fenton-like reactions also caused DNA double-strand breaks. HPLC measurements showed that .OH radicals generated by Cr(IV) and Cr(V) from H2O2 caused 2'-deoxyguanine hydroxylation to form 8-hydroxy-2'-deoxyguanine.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1994

Myocardial stunning: association with altered gene expression.

Regional and global myocardial ischemia and reperfusion have been demonstrated to induce expression of the stress response protein heat shock 70 (HSP70) and of immediate early genes, c-jun, c-fos, and c-myc. Because of the models that have been utilized, it has not been possible to discriminate whether this response is the consequence of ischemia, reperfusion, or abnormal hemodynamic stress superimposed on stunned myocardium. In a nonworking isolated and blood-perfused rat heart model, we evaluated the mRNAs for c-fos, c-myc, and hsp70. The heart was subjected to varying periods of ischemia and reperfusion. Significant increases in hsp70 and c-fos were observed, which increased with longer periods of ischemia. No significant increase in c-myc was measured. In addition, mRNA encoding the Ca2+/glucose responsive stress protein GRP78 was evaluated. No increase in this early response gene was noted despite the use of a model associated with cellular calcium loading. Based on these observations, we suggest that the induction of hsp70 and c-fos is the consequence of ischemia and reperfusion and not dependent upon an early hypertrophy response such as would be observed in afterload mismatching or on calcium loading. Further investigations are necessary to isolate the effects of ischemia from those of reperfusion.

Animals↗
PubMed1994

Association of rotating shiftwork with preterm births and low birth weight among never smoking women textile workers in China.

1035 married women workers in three modern textile mills in Anhui, China were surveyed to investigate the association of rotating shiftwork with low birth weight and preterm birth in 1992. Information on reproductive health, occupational exposure history, and other covariates including age at pregnancy, time and duration of leave from job since pregnancy, and mill location was obtained by trained nurses with a standardised questionnaire. This analysis was limited to 845 women (887 live births), who were middle or high school graduates, never smokers, and non-alcohol drinkers. About 72% of the women worked an eight day cycle with shift changes every two days throughout pregnancy. Mean gestational age was 38.8 and 39.0 weeks for shift and regular schedule workers, respectively. Multiple linear regression was used to adjust for confounding factors including maternal age at pregnancy, order of live birth, mill location, job title, occupational exposure to dust/gases/fumes, stress, carrying and lifting of heavy loads, working in a squat position, time and duration of leave from the job since pregnancy, and indoor coal combustion for heating. The adjusted difference in gestational age associated with rotating shifts was statistically significant (beta = -0.44 (SE 0.20) weeks.) Mean birth weights were 3248 g and 3338 g for rotating shift workers and regular schedule workers respectively. The estimated effect of rotating shiftwork on birth weight was -79 (SE 42) g. When the analysis was restricted to first order live births or to production workers, the estimated effects of rotating shiftwork on both gestational age and birth weight were significant. The proportions of preterm birth (<37 weeks) and low birth weight (<2500 g), respectively, were 20% and 9% for shift workers and 15% and 6% for regular schedule workers. The adjusted odds ratio of shiftwork was 2.0 (95% CI) 1.1-3.4) for preterm birth and 2.1 (95% CI 1.1-4.1) for low birth weight. This association remained significant when the analysis was restricted to production workers or first order live births.

Adult↗
PubMed1994

[The effect of Sindbis virus multiplication on gene expression of host cells].

Sindbis virus (SBV) infection mediated a rapid shutoff of host cellular gene expression (mRNA synthesis and protein synthesis); however the synthesis of cellular rRNA remained at the same level as the uninfected cells. Meanwhile a cellular protein P105 was shown to be enriched in the nuclear matrix. Actionmycin D treatment after virus infection resulted in an apparent reduce in the production of viral structural proteins and infectious virions. The results presented here not only demonstrated the complexity of SBV-mediated regulation of host gene expression, but also suggested SBV nonstructural protein nsP2 and capsid protein C were possibly involved in this process.

Animals↗