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H Li

Publications and source records attributed to H Li.

At least 1,081 records · Page 60Linked to original sources
PubMed1998

Brain mitochondria catalyze the oxidation of 7-(2-aminoethyl)-3,4-dihydro-5-hydroxy-2H-1,4-benzothiazine-3-carboxyli c acid (DHBT-1) to intermediates that irreversibly inhibit complex I and scavenge glutathione: potential relevance to the pathogenesis of Parkinson's disease.

We have proposed that a very early step in the pathogenesis of idiopathic Parkinson's disease is the elevated translocation of L-cysteine into neuromelanin-pigmented dopaminergic neurons in the substantia nigra. This influx of L-cysteine was proposed to divert the normal neuromelanin pathway by scavenging dopamine-o-quinone, formed by autoxidation of cytoplasmic dopamine, to give initially 5-S-cysteinyldopamine, which is further oxidized to 7-(2-aminoethyl)-3,4-dihydro-5-hydroxy-2H-1,4-benzothiazine-3-carboxylic acid (DHBT-1). In a recent report, it was demonstrated that DHBT-1 evokes inhibition of complex I respiration when incubated with intact rat brain mitochondria and a time-dependent irreversible inhibition of NADH-coenzyme Q1 (CoQ1) reductase when incubated with mitochondrial membranes. In this study, it is established that the time dependence of NADH-CoQ1 reductase inhibition reflects the oxidation of DHBT-1, catalyzed by an unknown constituent of the inner mitochondrial membrane, to an o-quinone imine intermediate that rearranges to 7-(2-aminoethyl)-5-hydroxy-1,4-benzothiazine-3-carboxylic acid (BT-1) and decarboxylates to 7-(2-aminoethyl)-5-hydroxy-1,4-benzothiazine (BT-2), which are further catalytically oxidized to o-quinone imine intermediates. The electrophilic o-quinone imine intermediates formed in these mitochondria-catalyzed oxidations of DHBT-1, BT-1, and BT-2 are proposed to bind covalently to key sulfhydryl residues at the complex I site, thus evoking irreversible inhibition of NADH-CoQ1 reductase. Evidence for this mechanism derives from the fact that greater than equimolar concentrations of glutathione completely block inhibition of NADH-CoQ1 reductase by DHBT-1, BT-1, and BT-2 by scavenging their electrophilic o-quinone imine metabolites to form glutathionyl conjugates. The results of this investigation may provide insights into the irreversible loss of glutathione and decreased mitochondrial complex I activity, which are both anatomically specific to the substantia nigra and exclusive to Parkinson's disease.

Animals↗
PubMed1998

A rat model of chronic Helicobacter pylori infection. Studies of epithelial cell turnover and gastric ulcer healing.

BACKGROUND: Our aim was to infect rats with Helicobacter pylori and to study the effects of the infection on the gastric mucosa in normal and in ulcer-operated rats. METHODS: A mouse-adapted H. pylori (cagA-, VacA-) strain was inoculated into 23 rats. Another 20 uninfected rats served as controls. Two months later a gastric ulcer was induced in some rats. The animals were killed 3, 6, or 15 days after the ulcer operation. Tissues were taken for histology and for culture of H. pylori. Serum antibodies were determined. RESULTS: All inoculated rats were infected by H. pylori after 2 months, mainly in the antrum. In these rats a mild to moderate chronic inflammation and a significantly increased frequency of apoptotic cells were observed in the antrum and in the ulcer margin, the ulcer healing was delayed, and the serum level of H. pylori-specific Ig was increased. CONCLUSIONS: H. pylori infection in rats was successful and was accompanied by a mild to moderate mucosal inflammation. Gastric ulcer healing was delayed in infected rats, probably due to the inflammation and the increased apoptosis in epithelium.

Animals↗
PubMed1998

Comparative health risk assessment of nuclear power and coal power in China.

The public health risk of ionising radiation released from the coal-fired energy chain, 20 deaths (GW a)(-1), is about 18 times that of the nuclear energy chain, 1.1 deaths (GW a)(-1), in China. The main contributors to the fatality risk for the former are the public dose caused by the use of coal ash and the occupational exposure caused by radon and its progeny in coal mines. The total health risk (but excluding low probability/high consequence accidents) of the coal-fired energy chain, 57.1 deaths (GW a)(-1), is about 12 times of that of the nuclear energy chain, 4.6 deaths (GW a)(-1). The health risk of coal-fired energy chain could be significantly reduced if technique and management were improved. Even then the risk of the coal-fired energy chain is about 4.4 times that of the nuclear energy chain.

China↗
PubMed1998

Nuclear factor-1 motif and redundant regulatory elements comprise phenobarbital-responsive enhancer in CYP2B1/2.

Although the induction of drug-metabolizing systems by phenobarbital has been recognized for about 40 years, the mechanism by which cytochrome P450 gene expression is increased is still not well understood. A 163-bp fragment at about -2.2 Kb in CYP2B2 has been shown to mediate phenobarbital induction in primary rat hepatocytes (Trottier, et al. [1995] Gene 158:263-268) and by an in situ transient transfection assay in rat liver (Park, Y., et al. [1996]. J. Biol. Chem. 271:23725-23728). Deletion mutations of this fragment indicated that the 88-bp stretch from -2258 to -2170 was the minimal sequence that could mediate phenobarbital induction in the in situ system if single copies of the deleted fragments fused to the CYP2C1 proximal promoter were assayed. If three copies of the fragments were present, 5' and 3' deletions defined a minimal 37-bp core fragment, which, although necessary for phenobarbital responsiveness, was not sufficient unless additional sequence was present at either end, suggesting that redundant elements were present in the two flanking regions. Site-specific mutagenesis of an NF-1 site within the 88-bp fragment and linker scanning mutagenesis across the fragment indicated that the NF-1 site and a region to the 5' side of the site contributed to the magnitude of the response, but neither the NF-1 mutations nor any of the linker scanning mutations eliminated the response to phenobarbital. Mutation in a region 3' of the NF-1 site resulted in elevated basal expression without substantial effects on phenobarbital-induced expression. Binding of NF-1 to the 37-bp core fragment was established by gel-shift competition studies and by supershifts of the protein-DNA complexes by antisera to NF-1. Additional protein-DNA complexes were detected in the regions flanking the NF-1 site. These studies indicate that the CYP2B2 phenobarbital-responsive enhancer contains multiple constitutive and phenobarbital-responsive elements. Binding of nuclear proteins from control or phenobarbital-treated animals in vitro to this region was very similar. The only difference detected was a complex that was substantially reduced by phenobarbital treatment and mapped to the 3' side of the NF-1 site.

Animals↗
PubMed1998

Structural similarities between hammerhead ribozymes and the spliceosomal RNAs could be responsible for lack of ribozyme cleavage in yeast.

Hammerhead ribozymes have been proposed as potential therapeutic agents for the treatment of viral and other diseases. However, a clear understanding of the cleavage reaction in vivo is not available at present. In these studies, we chose the yeast Saccharomyces cerevisiae as a model system to study the effects of hammerhead cleavage on gene expression in vivo. Several reporter genes were employed to monitor the self-cleaving characteristics of three different ribozymes. We show that these ribozymes decrease expression of some reporter genes by interfering with splice site selection or translation initiation and not by in vivo cleavage of the RNA transcripts. In fact, it appears that although these ribozymes can efficiently self-cleave the RNA in vitro, they are not able to function in vivo. We have identified a yeast splicing protein that interacts in vivo with our cis-ribozyme by specifically recognizing the ribozyme structure (Lin and Rossi, 1996). This interaction does not occur if different secondary structures are used in place of the ribozyme. The binding of this protein to the ribozyme can account for the inability of ribozymes to efficiently cleave in yeast. Remarkably, when yeast extracts are added to in vitro trans-cleavage reactions, the cleavage ability of the ribozyme is hampered, whereas the addition of mammalian extracts yields an enhancement of the reactions. These results confirm the presence of factor(s) that can block ribozyme function in the yeast intracellular environment.

Base Sequence↗
PubMed1998

Virion encapsidation of tRNA(3Lys)-ribozyme chimeric RNAs inhibits HIV infection.

Retroviruses require a specific host cellular tRNA primer for initiation of first-strand DNA synthesis. This primer is bound by viral proteins and copackaged into virions. We have exploited this property in the design and testing of an antiviral ribozyme fused to tRNA(3Lys), the primer used for lentiviral replication, including human immunodeficiency virus (HIV-1 and HIV-2). The chimera consists of tRNA(3Lys) covalently attached to a hammerhead ribozyme, which is targeted to the region immediately upstream of the primer binding site of the HIV-1 genome. The tRNA-ribozyme chimeric transcript is catalytically active in vitro and is efficiently bound by HIV reverse transcriptase with an affinity similar to that of tRNA(3Lys). We have expressed the chimeric RNAs from either the tRNA(3Lys) intragenic RNA polymerase III promoter or from a human U6 snRNA promoter. The U6 promoter results in up to 10-fold enhanced expression of the tRNA-ribozyme. Most importantly, the tRNA(3Lys)-ribozymes are encapsidated in HIV-1 virions such that they are effective in substantially reducing the level of infectious virus produced from cells cotransfected with HIV-1 proviral DNA. These results demonstrate the feasibility of using this novel strategy to reduce HIV infectivity and more generally indicate the potential power of using the retroviral primer tRNAs as tools for expressing and delivering ribozymes and other antiretroviral RNAs to the virion capsid.

Anti-HIV Agents↗
PubMed1998

Unusual interactions between cleavage products of a cis-cleaving hammerhead ribozyme.

We have synthesized and tested a cis-cleaving ribozyme designed to have thermodynamically stable stem-loop structures. This cis-ribozyme cleaves very efficiently in vitro, with a cleavage rate of about 0.5/min. Surprisingly, during the course of in vitro transcription and cleavage of our ribozyme, a product of unusual mobility accumulates and coincides with a sharp decline in the rate of formation of cleavage products. Analyses of this electrophoretic variant demonstrated that it is formed by interactions of the cleavage products. Despite the fact that the products and ribozyme transcript are of identical sequence, the cleavage products interact only with one another and not with the uncleaved precursor. This suggests a significant structural difference between the cleaved and uncleaved ribozyme transcripts. Testing of this cis-ribozyme in both yeast and mammalian cells shows no significant cleavage activity in vivo. We conclude that the structure of the ribozyme flanking sequences is important for optimizing the rate of ribozyme cleavage, but this enhanced rate does not necessarily correlate with enhanced in vivo function.

Bacteriophage T7↗
PubMed1998

Treatment of patients with toxic multinodular goiter.

The medical records of 253 patients evaluated for toxic multinodular goiter from 1975 through 1993 were reviewed to determine treatment trends, success, and complications. Of the 235 (93%) treated, 174 (74%) received surgical treatment and 61 (26%) received radioiodine (131I) treatment. Three months after initial treatment, 82% of surgically treated patients became euthyroid or hypothyroid compared with 21% of the 131I group. Among the 131I-treated patients, 20% required a second treatment, whereas none needed further treatment in the surgical group. At 2 years, the estimated probability of success was similar. The probability of post-treatment hypothyroidism was significantly higher for surgically treated patients, which is expected.

Adult↗
PubMed1998

Mutation at the anophthalmic white locus in Syrian hamsters: haploinsufficiency in the Mitf gene mimics human Waardenburg syndrome type 2.

Mutations in MITF (microphthalmia transcription factor) cause Waardenburg syndrome type 2 (WS2A) in humans, an autosomal dominant disorder consisting of deafness and hypopigmentation. Phenotypes vary significantly within WS2 pedigrees, and there is generally no correlation between the predicted biochemical properties of mutant MITF proteins and disease severity. We have identified a nonsense mutation in the Mitf gene of the anophthalmic white Wh) Syrian hamster that destabilizes its mRNA and prevents the encoded basic helix-loop-helix leucine zipper (bHLHzip) protein from dimerizing or binding DNA target sites. Although the resulting polypeptide does not act as a dominant-negative species in vitro , the Wh mutation is inherited as a semi-dominant trait. It thus more closely resembles WS2 than comparable Mitf alleles in laboratory mice and rats, which are expressed as purely recessive traits.

Amino Acid Sequence↗
PubMed1998

Experimental autoimmune myasthenia gravis induction in B cell-deficient mice.

Experimental autoimmune myasthenia gravis (EAMG) is an animal model for human myasthenia gravis (MG). Autoantibody-induced functional loss of nicotinic acetylcholine receptor (AChR) at the postsynaptic membrane is an important pathogenic feature of both MG and EAMG. To evaluate the extent at which the humoral immune response against AChR operates in the pathogenesis of EAMG, we immunized B cell knockout (muMT) and wild-type C57BL/6 mice with AChR and complete Freund's adjuvant. The ability of AChR-primed lymph node cells to proliferate and secrete IFN-gamma in response to AChR and its dominant peptide alpha146-162 were intact in muMT mice as in wild-type mice. Similar amounts of mRNA for IFN-gamma, IL-4 and IL-10 in AChR-reactive lymph node cells were detected in muMT and wild-type mice. However, muMT mice had no detectable anti-AChR antibodies and remained completely free from clinical EAMG. We conclude that B cells are critically required for the genesis of clinical EAMG, but not for AChR-specific T cell priming.

Animals↗
PubMed1998

Partial characterization of ovine intrauterine suppressor cells.

Ovine uterine cells that represented Day 14 cyclic and pregnant endometrium were fractionated with Percoll and evaluated for suppression of cocultured phytohemagglutinin (PHA)-induced peripheral blood lymphocyte (PBL) proliferation and for the presence of T-lymphocyte markers. Uterine cells were then evaluated for suppressor activity following the depletion of conventional lymphocyte classes (i.e., T-, B-, and NK-like) with complement + antibody treatment. In addition, supernatant (derived from cultured uterine cells) was tested for transforming growth factor beta (TGFbeta) activity using neutralization antibodies to TGFbeta. Fractionated uterine cells (density range of 1.002-1.056 g/ml) from cyclic and pregnant ewes suppressed PHA-induced proliferation of PBL, and the majority (69.5%) of these cells were < or = 5.2 microm in diameter. Percentages of CD5+, CD4+, and CD8+ lymphocytes recovered from endometrial curettage were less for cells in this density range than for cells with greater densities. Uterine cells released suppressor factor(s) into the culture medium (supernatant); however, suppressor activity was unaffected by either anti-TGFbeta or complement + antibody treatment. In conclusion, low-density uterine cells from Day 14 cyclic and pregnant ewes suppressed the proliferation of cocultured PBL and released a suppressor factor(s) into the medium that did not exhibit TGFbeta activity. It is unlikely that the suppressor cells comprise conventional T-, B-, or NK-like lymphocyte lineages.

Animals↗
PubMed1998

Complete replication of human sperm genome in egg extracts from Xenopus laevis.

To examine the ability of Xenopus egg extracts to support a complete replication cycle of human sperm genome, demembranated human spermatozoa were incubated with the extract from activated Xenopus laevis eggs. Most sperm heads were decondensed within 15 min. The heads became round within 30 min with diameters of 10-30 microns. The process of DNA replication in the pronuclei was monitored by two methods, bromodeoxyuridine incorporation and flow cytometry. The results indicate that DNA replication was initiated approximately 1.5 h after membrane structure formation and that it lasted up to 9 h. The amounts of DNA in most pronuclei were doubled by 4-9 h, depending on which donor toad was the source of the egg extract. Inclusion of the protein synthesis inhibitor, cycloheximide (100 micrograms/ml), had no obvious effect on human sperm DNA replication but appeared to prevent the pronuclei from degradation after a prolonged period (> 6 h) of incubation. After storage in liquid nitrogen for > 1.5 mo, the efficiency of the egg extracts in supporting sperm head decondensation and DNA replication was reduced for human sperm but not for Xenopus sperm. Possible applications of the use of Xenopus egg extract for human sperm activation and DNA replication are discussed.

Animals↗
PubMed1998

Immunoreactive endothelin-1 and its receptors in human adrenal tissues.

To elucidate the pathophysiologic significance of endothelin-1 (ET-1) in adrenal and the mechanism for reduced responsiveness to exogenous ET-1 in aldosterone-producing adenoma (APA), we have investigated ET-1 receptors by radioligand binding assay (RBA) in human normal adrenal (NA), APA, idiopathic hyperaldosteronism (IHA), and pheochromocytoma (PHEO), immunoreactive (ir-) ET-1 content in NA, APA and PHEO by radioimmunoassay (RIA), and immunohistochemical staining of ET-1 with the peroxidase-anti-peroxidase (PAP) method in NA, APA, and PHEO. A single class of high-affinity binding sites for ET-1 was found in human NA and tumor tissues. Dissociation constant (Kd) values of ET-1 receptors were similar in NA, APA, and IHA, but maximal binding capacity (Bmax) of ET-1 receptors was lower in APA than in NA and IHA. Both Kd and Bmax in PHEO were higher than those in NA, APA, and IHA. Ir-ET-1 content in tumors of APA and PHEO were higher than in NA. Immunohistochemical staining was more intense in the tumor cells of APA and PHEO than in NA. These results suggest that the reduced response to exogenous ET-1 in APA could be related to downregulation of ET-1 receptors in the tumor. Increased ET-1 content and receptors may lead to hypersecretion of catecholamine in PHEO. ET-1 produced in normal and tumor adrenal tissues may regulate aldosterone and catecholamine secretion from adrenals in a paracrine/autocrine fashion.

Adrenal Gland Neoplasms↗
PubMed1998

Arabidopsis Rho-related GTPases: differential gene expression in pollen and polar localization in fission yeast.

The Rho small GTP-binding proteins are versatile, conserved molecular switches in eukaryotic signal transduction. Plants contain a unique subfamily of Rho-GTPases called Rop (Rho-related GTPases from plants). Our previous studies involving injection of antibodies indicated that the pea Rop GTPase Rop1Ps is critical for pollen tube growth. In this study we show that overexpression of an apparent Arabidopsis ortholog of Rop1Ps, Rop1At, induces isotropic cell growth in fission yeast (Schizosaccharomyces pombe) and that green fluorescence protein-tagged Rop1At displays polar localization to the site of growth in yeast. We found that Rop1At and two other Arabidopsis Rops, Rop3At and Rop5At, are all expressed in mature pollen. All three pollen Rops fall into the same subgroup as Rop1Ps and diverge from those Rops that are not expressed in mature pollen, suggesting a coupling of the structural conservation of Rop GTPases to their gene expression in pollen. However, pollen-specific transcript accumulation for Rop1At is much higher than that for Rop3At and Rop5At. Furthermore, Rop1At is specifically expressed in anthers, whereas Rop3At and Rop5At are also expressed in vegetative tissues. In transgenic plants containing the Rop1At promoter:GUS fusion gene, GUS is specifically expressed in mature pollen and pollen tubes. We propose that Rop1At may play a predominant role in the regulation of polarized cell growth in pollen, whereas its close relatives Rop3At and Rop5At may be functionally redundant to Rop1At in pollen.

Amino Acid Sequence↗
PubMed1998

The mean ventricular fibrillation cycle length: a potentially useful parameter for programming implantable cardioverter defibrillators.

In programming the implantable cardioverter defibrillator (ICD), the ventricular tachycardia (VT) detection cycle length (CL) is based on the CL of the documented tachycardia but the ventricular fibrillation (VF) detection CL is set arbitrarily. Appropriate programming of VF detection may not only reduce the incidence of inappropriate ICD shocks for non-VF rhythms but can also avoid the fatal underdetection of VF. The mean VFCL may provide a useful parameter for optimal ICD programming for VF detection if it is reproducible. This study examined the intrapatient reproducibility and interpatient variation of the mean VFCL in 30 ICD patients (25 men and 5 women, mean age 63 +/- 13 years). A total of 210 VF episodes (7 +/- 4 per patient, range 3-17) induced by T-wave shocks (166) or AC (44) at the ICD implant (30 patients) and the predischarge test (12 of 30 patients) were analyzed. The mean VFCL was calculated from the stored V-V intervals in the ICDs. Although the mean VFCL varied significantly from 171 +/- 6 to 263 +/- 11 ms (P < 0.01) among different patients, it was reproducible among different VF episodes in an individual patient (maximal variation 4-50 ms, P > 0.05). The mean VFCL was not significantly different between patients with and without antiarrhythmic drugs (210 +/- 32 vs 210 +/- 23 ms, P > 0.05) and was correlated with the ventricular effective refractory period (r = 0.5, P < 0.05). The mean VFCL varies greatly among different patients but remains reproducible in an individual patient, suggesting that the mean VFCL may serve as a reference for ICD programming of VF detection.

Adult↗
PubMed1998

Structure-function studies of T-cell receptor-superantigen interactions.

Superantigens (SAGs) are a class of disease-causing and immunostimulatory proteins of bacterial or viral origin that activate T cells by binding to the V beta domain of the T-cell antigen receptor (TCR). The three-dimensional structure of the complex between a TCR beta chain (mouse V beta 8.2-J beta 2.1-C beta 1) and the SAG staphylococcal enterotoxin C3 (SEC3) has been recently determined. The complementarity-determining region 2 (CDR2) of the beta chain and, to lesser extents, CDR1 and hypervariable region 4 (HV4) bind in a cleft between the small and large domains of the SAG. A model of the TCR-SAG-peptide/MHC complex constructed from available crystal structures reveals how the SAG acts as a wedge between the TCR and MHC, thereby displacing the antigenic peptide away from the TCR and circumventing the normal mechanism for T-cell activation by peptide/MHC. To evaluate the actual contribution of individual SAG residues to stabilizing the V beta C beta-SEC3 complex, as well as to investigate the relationship between the affinity of SAGs for TCB and MHC and their ability to activate T cells, we measured the binding of a set of SEC3 mutants to a soluble recombinant TCR beta chain and to the human MHC class II molecule HLA-DR1. We show that there is direct correlation between affinity and ability to stimulate T cells, with SAGs having the highest affinity for the TCR being the most biologically active. We also find that there is an interplay between TCR-SAG and SAG-MHC interactions in determining mitogenic potency, such that a small increase in the affinity of a SAG for MHC can overcome a large decrease in the SAG's affinity for the TCR. Finally, we observe that those SEC3 residues that make the greatest energetic contribution to stabilizing the V beta C beta-SEC3 complex are strictly conserved among enterotoxins reactive with mouse V beta 8.2, thereby explaining why SAGs having other residues at these positions show different V beta-binding specificities.

Amino Acid Sequence↗
PubMed1998

Inhibitory effect of glycyrrhizin on NF-kappaB binding activity in CCl4- plus ethanol-induced liver cirrhosis in rats.

AIMS/BACKGROUND: Potenlini is an injectable compound whose active component is glycyrrhizin, which is extracted from licorice. Previous studies showed that it could reduce liver injury, improve alanine aminotransferase (ALT) levels and act as an antifibrotic agent. However, the mechanism of its action remains unclear. The aim of this study was to determine the molecular mechanism of its action by investigating the effects of potenlini on nuclear factor-kappaB (NF-kappaB) binding activity in an animal model of liver cirrhosis. METHODS: Rats were randomly allocated into a normal control group, a model control group, and a potenlini group. Rats in the latter two groups were treated with CCl4 and ethanol solution in order to induce chronic liver injury. Rats in the potenlini group were given potenlini treatment at the same time. RESULTS: Serum ALT levels were significantly reduced in rats treated with potenlini compared with levels in rats of the model control group, which had dramatically increased ALT levels. Histologically, liver steatosis and fibrosis were severe in the rats of the model group, but were significantly improved in rats of the potenlini group. NF-kappaB binding activity was markedly increased in the liver specimens taken from the rats of the model control group in comparison with the binding of normal livers, but the binding levels were nearly normal in the livers of the potenlini group. CONCLUSIONS: The results suggest that potenlini can inhibit the NF-kappaB binding activity in CCl4 and ethanol-induced chronic liver injury, and that effect may be a possible mechanism by which potenlini protects the liver from hepatotoxin-induced liver injury and cirrhosis.

Animals↗