Biomedical subjects

E Li

Publications and source records attributed to E Li.

At least 145 records · Page 8Linked to original sources

PubMed1995

Role of the Entamoeba histolytica cysteine proteinase in amebic liver abscess formation in severe combined immunodeficient mice.

Evidence from in vitro studies suggest that the Entamoeba histolytica cysteine proteinase plays a role in the tissue lysis and cytopathic effects seen in invasive amebiasis. We used affinity-purified antibodies against a recombinant E. histolytica cysteine proteinase to demonstrate that the proteinase is present extracellularly in amebic liver abscesses in mice with severe combined immunodeficiency (SCID mice). Treatment of E. histolytica trophozoites with specific cysteine proteinase inhibitor E-64 blocked or greatly reduced liver abscess formation at 48 h in SCID mice. Our study suggests an important role for a functional cysteine proteinase in amebic liver abscess formation.

Animals↗

PubMed1995

[Influence of dihydroetorphine hydrochloride and tramadol on labor pain and umbilical blood gas].

Ninety primigravide were randomly allocated into three groups at the beginning of active phase of labor. Dihydroetorphine hydrochloride (DHE) was administered to group A (n = 30), tramadol to group B (n = 30), and group C (n = 30) was a blank control. Various parameters about analgesia effects, progress of labour and fetal and neonatal well-being were investigated and also umbilical artery and vein blood gases analyzing were carried out in all cases. As a result, the effective rate of pain relief in group A was 67% and in group B 63% (P > 0.05). The average time of onset of action in DHE group was 16.5 +/- 2.9 minutes which was significantly shorter than 26.1 +/- 5.4 minutes in tramadol group (P = 0.0001). There were higher rate (36.7%) of operative intervention (forceps and vaginally or cesarean section) and a higher average amount of postpartum hemorrhage in group A, as compared with the control group, but no significant difference was shown between group B and group C. No difference was found in other parameters (among the three groups duration of labour, Apgar scores of neonates, cord blood gases, etc.). The conclusion is that, both DHE and tramadol may have a good effect of pain relief in labour. The time of onset of action in DHE group is significantly shorter than that in tramadol group. Neither analgesics cause circulation and respiratory depression in the mother and neonates, but DHE may have influence on uterine contraction. To achieve an excellent pain relief by higher dosage of DHE and tramadol need further randomized investigation.

Analgesia, Obstetrical↗

PubMed1995

[Effect of bushen shengxue recipe on EPO gene expression of chronic renal insufficiency anemia in rats].

The rats were fed with adenine to establish the chronic renal insufficiency anemia model, and the relationship between renal functional impairment and reticulocytes, hemoglobin and erythropoietin (EPO) synthesis was observed to explore the mechanism of Bushen Shengxue drugs in improving the hemopoietic function. The results showed that the Bushen Shengxue drugs could significantly lower the serum creatinine and blood urea nitrogen of renal insufficiency rats, and through the promotion of EPO gene expression, the animals' anemic status was improved.

Anemia↗

PubMed1994

Toxicity of 5-aza-2'-deoxycytidine to mammalian cells is mediated primarily by covalent trapping of DNA methyltransferase rather than DNA demethylation.

The deoxycytidine analog 5-aza-2'-deoxycytidine (5-azadCyd) has been widely used as a DNA methylation inhibitor to experimentally induce gene expression and cellular differentiation. Prior to the availability of mutant mice with altered DNA methyltransferase levels, treatment of cells with drugs has been the only means to experimentally manipulate the level of genomic DNA methylation in mammalian cells. Substitution of DNA with 5-azadCyd leads to covalent trapping of the enzyme, thereby depleting the cells of enzyme activity and resulting in DNA demethylation. 5-AzadCyd or 5-azacytidine treatment causes multiple changes in treated cells, including activation of silent genes, decondensation of chromatin, and induction of cellular differentiation, all of which are believed to be consequences of drug-induced demethylation. 5-AzadCyd is highly toxic in cultured cells and animals and is utilized as a potent antitumor agent for treatment of certain human cancers. It has been postulated that the toxicity of the drug in mammalian cells is also due to its inhibition of DNA methylation. The chemistry of the methylation reaction is consistent, however, with an alternative mechanism: the cytotoxic effect of 5-azadCyd may be directly mediated through the covalent binding of DNA methyltransferase to 5-azadCyd-substituted DNA. We have tested this possibility by using embryonic stem cells and mice with reduced levels of DNA methyltransferase due to a targeted mutation of the gene. When exposed to 5-azadCyd mutant embryonic stem cells or embryos were significantly more resistant to the toxic effects of the drug than wild-type cells and embryos, respectively. These results strongly suggest that the cellular DNA methyltransferase itself, rather than the secondary demethylation of genomic DNA, is the primary mediator of 5-azadCyd cytotoxicity. In light of our results, some conclusions from previous studies using 5-azadCyd in order to experimentally manipulate cellular methylation levels may have to be reassessed. Also, our data make clear predictions for cancer treatment: tumor cells with elevated DNA methyltransferase levels would be expected to be susceptible to treatment with 5-azadCyd, whereas tumors with reduced levels of the enzyme would be resistant.

Animals↗

PubMed1994

Measurement of subnanomolar retinoic acid binding affinities for cellular retinoic acid binding proteins by fluorometric titration.

Cellular retinoic acid binding protein I (CRABP-I) and cellular retinoic acid binding protein II (CRABP-II) are small, cytoplasmic proteins which bind all-trans-retinoic acid with high affinity. Both of these proteins belong to a family of intracellular proteins which bind amphiphilic lipids, including fatty acids, bile salts, and retinoids. Because CRABP-I and -II exhibit different tissue distributions and differential transcriptional regulation, they are proposed to serve different functions. The binding properties of mouse CRABP-I and -II purified from Escherichia coli were examined to further understand their role in intracellular retinoic acid processing. Fluorescence titrations were performed using nanomolar protein concentrations, near the obtained dissociation constants, and analyzed by direct mathematical fitting to raw data, in order to extend the range and accuracy of binding constant determination. The apparent dissociation constants, K'd, of mouse CRABP-I and CRABP-II binding all-trans-retinoic acid were determined to be 0.4 +/- 0.3 nM and 2 +/- 1 nM respectively, stronger binding than previously reported. The K'd of mCRABP-I and mCRABP-II complexing with acitretin, a pharmacologically active synthetic retinoid used in the treatment of psoriasis, was 3 +/- 1 nM and 15 +/- 11 nM. Both CRABPs bound 9-cis-retinoic acid with a K'd of roughly 200 nM, and neither exhibited significant binding of 13-cis-retinoic acid.

Acitretin↗

PubMed1994

NMR studies of fluororetinol analogs complexed to two homologous rat cellular retinol-binding proteins.

Comparative 19F-NMR studies of fluororetinol analogs with rat cellular retinol binding protein II (CRBP II) and rat cellular retinol-binding protein (CRBP) were performed to probe differences in the binding interactions of these two homologous proteins. Line shape analyses of 19F-NMR spectra of (E,E,Z,E)-6-fluoro-9-(4-methoxy-2,3,6-trimethylphenyl)-3,7-dimethyl- 2,4,6,8-nonatetren-1-ol (ligand 1), (E,E,Z,E)-6-fluoro-9-(2,2' dimethyl-6-methylcyclohexenyl)-3,7- dimethyl-2,4,6,8-nonatetren-1-ol (ligand 2), (E,Z,E,E)-5-fluoro-9-(2,2'- dimethyl-6-methylcyclohexenyl)-3,7-dimethyl-2,4,6,8-nonatetren+ ++-1-ol (ligand 3), when complexed with CRBP II at temperatures ranging from 0-45 degrees C, revealed that the 19F resonances corresponding to the bound ligand were in slow chemical exchange between two resonance frequencies. This was further supported by a 2D-NOESY exchange experiment. The kex at 25 degrees C was estimated from spectral simulation and fitting analyses to be 887 s-1, 1010 s-1 and 771 s-1 for CRBP II complexed 1, 2, and 3, respectively. In contrast, only a single absorption was observed for bound ligands complexed with rat CRBP over this temperature range, suggesting that the conformational dynamics of retinol binding are different for these two closely homologous proteins.

Animals↗

PubMed1994

Characterization of the ligand binding domain of human retinoid X receptor alpha expressed in Escherichia coli.

In order to study the structural details of ligand protein interactions of the human retinoid X receptor alpha (hRXR alpha), the DEF and EF domains of the receptor were expressed as glutathione S-transferase (GST) fusion proteins in Escherichia coli. The fusion proteins were expressed at high levels and were affinity-purified by chromatography over glutathione-agarose. The DEF and EF domains were cleaved from the fusion proteins by digestion with thrombin. Retinoic acid binding was quantitated using two different methods. The apparent dissociation constant (Kd) and the stoichiometry of 9-cis-retinoic acid binding were performed by monitoring quenching of protein fluorescence. To directly compare the binding affinity of the E. coli-derived truncated hRXR alpha with full-length hRXR alpha expressed in transiently transfected COS cells, Scatchard analyses of [3H]9-cis-retinoic acid binding assays were performed. Both methods of analysis indicate that while the cleaved DEF peptide bound 9-cis-retinoic acid tightly, the cleaved EF peptide exhibited variable binding activity between preparations. By fluorimetric analysis, the Kd of the cleaved DEF peptide was estimated to be 3 +/- 0.5 nM with a stoichiometry of 1:1.1 +/- 0.1. By Scatchard analysis, the Kd values for [3H]9-cis-retinoic acid to the GST-hRXR alpha (DEF) peptide and the cleaved DEF peptide were estimated to be 1.8 nM and 5.6 nM, respectively. The estimated molecular mass from high speed sedimentation equilibrium experiments was 36 +/- 2 kDa for the apo-DEF peptide alone and 38 +/- 3 kDa for the holo-DEF peptide complexed with 9-cis-retinoic acid. This suggests that the recombinant ligand binding domain was predominantly in the monomer form. However, dimers of the cleaved DEF peptides were detected in chemical cross-linking experiments both in the presence and absence of 9-cis-retinoic acid. Since the purified E. coli-derived truncated hRXR alpha DEF peptide appears to fully retain its ligand binding activity, it should provide a useful model system for further structural analysis of ligand-protein interactions.

Amino Acid Sequence↗

PubMed1994

A nonstationary Poisson point process describes the sequence of action potentials over long time scales in lateral-superior-olive auditory neurons.

The behavior of lateral-superior-olive (LSO) auditory neurons over large time scales was investigated. Of particular interest was the determination as to whether LSO neurons exhibit the same type of fractal behavior as that observed in primary VIII-nerve auditory neurons. It has been suggested that this fractal behavior, apparent on long time scales, may play a role in optimally coding natural sounds. We found that a nonfractal model, the nonstationary dead-time-modified Poisson point process (DTMP), describes the LSO firing patterns well for time scales greater than a few tens of milliseconds, a region where the specific details of refractoriness are unimportant. The rate is given by the sum of two decaying exponential functions. The process is completely specified by the initial values and time constants of the two exponentials and by the dead-time relation. Specific measures of the firing patterns investigated were the interspike-interval (ISI) histogram, the Fano-factor time curve (FFC), and the serial count correlation coefficient (SCC) with the number of action potentials in successive counting times serving as the random variable. For all the data sets we examined, the latter portion of the recording was well approximated by a single exponential rate function since the initial exponential portion rapidly decreases to a negligible value. Analytical expressions available for the statistics of a DTMP with a single exponential rate function can therefore be used for this portion of the data. Good agreement was obtained among the analytical results, the computer simulation, and the experimental data on time scales where the details of refractoriness are insignificant.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗

PubMed1994

Entamoeba histolytica has an alcohol dehydrogenase homologous to the multifunctional adhE gene product of Escherichia coli.

Entamoeba histolytica ferments glucose to ethanol under the anaerobic conditions of the human colon. There is special interest in this metabolic pathway because it provides an opportunity for parasite-specific chemotherapy. Peptide sequences from a 97-kDa E. histolytica protein, which was originally isolated because of extracellular matrix binding properties, were used to clone and sequence a gene that was found to encode an E. histolytica alcohol dehydrogenase and acetaldehyde dehydrogenase (EhADH2). The EhADH2 cDNA clone had an open reading frame encoding 870 amino acids with a predicted molecular weight of 95,758. The EhADH2 cDNA clone was identical in 48% of its amino acids to the multifunctional enzyme (alcohol dehydrogenase, acetyl-CoA reductase, and pyruvate-formate-lyase-deactivase) encoded by the Escherichia coli adhE gene. The isolation of the EhADH2 protein helps define a new family of ADH enzymes that may be specific to anaerobic and facultatively anaerobic organisms.

Alcohol Dehydrogenase↗

PubMed1994

Hemorrhagic fever with renal syndrome: relationship between pathogenesis and cellular immunity.

After phenotype analysis of peripheral blood mononuclear cells (PBMC), soluble interleukin-2 receptor (sIL-2R) levels in plasma or sera from patients with hemorrhagic fever with renal syndrome (HFRS) were measured. The results showed the ratio of activated antigen (CD25, TLiSA1, CD71, and Ia)-positive lymphocytes of PBMC in the acute phase of HFRS was higher than that in convalescent phase. Moreover, there was much higher expression of heteromorphologic lymphocytes than of small lymphocytes. Decreases in T lymphocytes and CD4:CD8 ratios were seen with increases in B lymphocyte ratios and interferon-gamma (IFN-gamma) expression on PBMC surfaces in the acute phase of HFRS. IFN-gamma-positive lymphocytes included CD4, CD8, and CD56 subsets. sIL-2R levels were much higher in sera and plasma in the acute phase, especially the oliguric phase. These findings suggest that patients with HFRS are in a state of high-level cellular immune response, which may be involved in the development of inflammation and pathologic lesions.

Acute Disease↗

PubMed1994

Entamoeba histolytica interactions with polarized human intestinal Caco-2 epithelial cells.

To model the initial pathogenic effects of Entamoeba histolytica trophozoites on intestinal epithelial cells, the interactions of E. histolytica HM1-IMSS trophozoites with polarized human intestinal Caco-2 cell monolayers grown on permeabilized filters were examined. Trophozoites, when incubated with the apical surface of the monolayers at 37 degrees C, induced a rapid decrease in transepithelial resistance over 15 to 60 min. The transmonolayer resistance response was not associated with changes in short-circuit current but was associated with an increase in mannitol flux, suggesting that the drop in resistance reflected a nonselective increase in epithelial permeability rather than stimulation of electrogenic ion transport. This response preceded the earliest detection of morphologic disruption of monolayer integrity by light or electron microscopy. Apical injury to the monolayer was detected by ultrastructural studies which revealed a loss of brush border in regions of contact between epithelial cells and amebas and by chromium release assays where a small increase in the apical release of 51Cr from the monolayer (6% over background) was observed. The transmonolayer resistance response was inhibited when the temperature was reduced to 4 degrees C and by addition of cytochalasin D (1 microgram/ml) to the medium at concentrations that did not directly affect transmonolayer resistance. Application of amebic lysates or medium conditioned by coincubation of amebas with Caco-2 monolayers failed to lower transmonolayer resistance, suggesting that this effect was not mediated by soluble amebic cytotoxins. Polarized Caco-2 monolayers grown on permeable filters provide a useful model for studying the initial interactions of E. histolytica trophozoites with intestinal epithelial cells.

Animals↗

PubMed1994

Ultrastructural observations of the anterior chamber angle tissues in congenital glaucoma.

Eighteen trabeculectomy specimens of congenital glaucoma were examined by light and transmission electron microscopy. The results showed that the primary anomalies in congenital glaucoma included the developmental defects of trabecular meshwork, excessive collagen fibrils in the trabecular matrix, shifting forward of ciliary muscle fibres and persistent mesenchymal tissues in the anterior-chamber angle. The authors also pointed out the importance of the secondary lesions of the trabecular meshwork in the pathogenesis of congenital glaucoma.

Anterior Chamber↗

PubMed1994

[Pick's disease in senescence].

We report two patients with Pick's disease in senescence. Patient 1 is a 78-year-old woman. She developed abnormal behavior at the age of 76 years. Neurological examination at age 76 revealed poor rapport, easy angriness, "Denkfaulheit", oral tendency, and slight dementia [WAIS (Wechsler Adult intelligence Scale) total IQ 62]. Cranial CT scan and MRI showed bilateral atrophy of the frontal and temporal lobe, especially of the temporal lobe. Patient 2 is a 73-year-old man. He developped sexual abnormal behavior and "triebhafte Hemmungslossigkeit" at the age of 71 years. Neurological examination at age 72 revealed poor rapport, lack of spontaneity, easy angriness, "Denkfaulheit", and slight dementia [WAIS total IQ 91]. Transient "stehende Redensarten" was noticed. Cranial CT scan and MRI showed bilateral atrophy of the frontal and temporal lobe, especially of the frontal lobe. To our knowledge, Pick's disease with an onset in the senescence is very rare. Pick's disease should be included in the differential diagnosis of abnormal behavior in the senescence.

Aged↗

PubMed1994

[15-Methyl-PGF2 alpha vaginal suppository for induction of term labor].

The results of intravaginal 15-methyl PGF2 alpha (PG05) were compared with gemeprost (ONO-802, PGE1 analogue) pessary and oxytocin intravenous infusion for induction of labor at term. A total of 99 primipara with singleton pregnancy and cephalic presentation, accepted for induction, was randomly allocated into 3 groups: group 1, PG05 0.25 mg (n = 33), group 2, ONO-802 0.125 mg (n = 33), and group 3, oxytocin i.v. (n = 33). Among these, 30 cases had plasma PGs (PGE2 and PGF2 alpha) concentration determined before and after induction. Successful treatment was defined as active labor starting within 24 hours following induction or an increase of cervical Bishop score > 3. The success rates were not significantly different among the 3 groups (PG05 88%, ONO-802 100%, and oxytocin 79%), (P > 0.05). No significant difference existed in the plasma prostaglandin concentrations as well. It is suggested that PG05 may be used for induction of labor at term.

Adult↗

PubMed1994

[Presenile dementia with marked recent memory disturbance--in relation to hippocampal dementia].

Two cases of presenile dementia with marked recent memory disturbance were reported. Patient 1 is a 54-year-old woman. She noticed forgetfulness at the age of 51 years. Neurological examination at aged 52 revealed marked recent memory disturbance, but examination by WAIS (Wechsler Adult Intelligence Scale) showed good results (verbal IQ 106, performance IQ 104, total IQ 106). There was neither disorientation in place nor character change. Cranial CT scan and MRI revealed the absence of brain atrophy. About 3 years after the onset of the disease, the degree of dementia is slight and disorientation in place does not appear. Patient 2 is a 67-year-old man. He noticed forgetfulness at the age of 63 years. Neurological examination at aged 66 revealed marked recent memory disturbance, but examination by WAIS-R showed moderate results (verbal IQ 89, performance IQ 87, total IQ 88). There was neither disorientation in place nor character change. Cranial CT scan and MRI revealed slight dilatation of the inferior horns of the lateral ventricle and slight cortical atrophy. About 4 years after the onset of the disease, the degree of dementia was slight and disorientation in place did not appear. We can not rule out the possibility that our cases belong to Alzheimer's disease, but the clinical course of our cases is peculiar. In the relation of responsible lesion in pure amnestic syndrome, hippocampal dementia, and simple senile dementia, our cases are interesting and important.

Aged↗

PubMed1993

Role for DNA methylation in genomic imprinting.

The paternal and maternal genomes are not equivalent and both are required for mammalian development. The difference between the parental genomes is believed to be due to gamete-specific differential modification, a process known as genomic imprinting. The study of transgene methylation has shown that methylation patterns can be inherited in a parent-of-origin-specific manner, suggesting that DNA methylation may play a role in genomic imprinting. The functional significance of DNA methylation in genomic imprinting was strengthened by the recent finding that CpG islands (or sites) in three imprinted genes, H19, insulin-like growth factor 2 (Igf-2), and Igf-2 receptor (Igf-2r), are differentially methylated depending on their parental origin. We have examined the expression of these three imprinted genes in mutant mice that are deficient in DNA methyltransferase activity. We report here that expression of all three genes was affected in mutant embryos: the normally silent paternal allele of the H19 gene was activated, whereas the normally active paternal allele of the Igf-2 gene and the active maternal allele of the Igf-2r gene were repressed. Our results demonstrate that a normal level of DNA methylation is required for controlling differential expression of the paternal and maternal alleles of imprinted genes.

Alleles↗

PubMed1993

Inter-tryptophan distances in rat cellular retinol binding protein II by solid-state NMR.

Structural constraints for the tryptophans in rat cellular retinol binding protein II (CRBP II) have been obtained by rotational-echo double-resonance (REDOR) solid-state NMR. CRBP II was labeled with L-[6-19F]tryptophan and L-[2-13C]tryptophan. The 13C-19F dipolar coupling was determined for various possible tryptophan geometries. The allowed distance between the closest two of the four tryptophans in CRBP II was obtained for each geometry. The minimum possible distance between these two tryptophans in CRBP II is 7 A, and the maximum possible distance is 11 A.

Animals↗

PubMed1993

Differential binding of retinol analogs to two homologous cellular retinol-binding proteins.

A comparative study of the interactions of rat cellular retinol-binding protein (CRBP) and cellular retinol-binding protein II (CRBP II) with a number of synthetic phenyl-substituted analogs of all-trans-retinol was performed using fluorescence and nuclear magnetic resonance analysis. These studies indicate that CRBP II is more sensitive to modifications of the ring moiety than CRBP. Removal of the two methyl substituents on the ring which are ortho to the polyene chain abolishes binding to CRBP II. Conformational analysis of the ligands indicates that these two methyl groups influence the planarity of the ligand. The identification of monospecific ligands may prove useful for studying the physiological roles of these two proteins.

Animals↗