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Biomedical subjects

T Li

Publications and source records attributed to T Li.

At least 91 records · Page 5Linked to original sources
PubMed2001

The mammalian retinal degeneration B2 gene is not required for photoreceptor function and survival.

The retinal degeneration B (rdgB) gene in Drosophila is essential for photoreceptor function and survival. The rdgB mutant fly exhibits an abnormal electroretinogram and a light-dependent photoreceptor degeneration. The function of RdgB is not fully understood, but the presence of a phosphatidylinositol transfer protein domain suggests a possible role in phosphatidylinositol metabolism and signaling. Two mammalian homologs, M-RdgB1 and M-RdgB2, are known. While M-RdgB1 is widely expressed, M-RdgB2 is found primarily in the retina and the dentate gyrus. Functional conservation between the Drosophila and mammalian RdgBs was demonstrated by the ability of both M-RdgBs to rescue the photoreceptor phenotype in rdgB mutant flies through transgenic expression. To investigate the role of M-RdgB2 in the mammalian retina, we disrupted the m-rdgB2 gene in mice by gene targeting. The homozygous knockout mice are fertile and apparently healthy. By light microscopy, immunocytochemistry and electroretinograms, mice up to 18 months of age showed normal photoreceptor function and survival. The inner retinal neurons were also examined by immunolabeling with a number of cell-specific markers and no apparent defects were found in the major cell populations. We conclude that M-rdgB2 is not essential for phototransduction and photoreceptor survival. Thus, m-rdgB2 is not a candidate gene for human retinal degenerations. Whether M-rdgB2 has a role in visual processing in the inner retina, or whether it is required for hippocampal function, remains to be determined.

Amacrine Cells↗
PubMed2001

Disease model: photoreceptor degenerations.

Retinal diseases can be caused by genetic or non-genetic factors, and typically involve specific cell layers within the retina. A large number of simple Mendelian gene defects are known to affect the photoreceptor cell layer. As photoreceptor cells cannot be maintained in vitro, the study of animal models is instrumental in understanding the disease process and in testing therapeutic approaches. This review briefly summarizes those animal models of photoreceptor diseases with defined genotypes.

Animals↗
PubMed2001

Cost inefficiency in Washington hospitals: a stochastic frontier approach using panel data.

We analyze a sample of Washington State hospitals with a stochastic frontier panel data model, specifying the cost function as a generalized Leontief function which, according to a Hausman test, performs better in this case than the translog form. A one-stage FGLS estimation procedure which directly models the inefficiency effects improves the efficiency of our estimates. We find that hospitals with higher casemix indices or more beds are less efficient while for-profit hospitals and those with higher proportion of Medicare patient days are more efficient. Relative to the most efficient hospital, the average hospital is only about 67% efficient.

Data Collection↗
PubMed2001

Genetic structure of populations of the human hookworm, Necator americanus, in China.

Twenty-one to 58 individual Necator americanus were sampled from each of four villages in south-western China. Each nematode was sequenced for 588 bp of the mitochondrial cytochrome oxidase I gene. Allelic and nucleotide diversity varied two-fold among villages. Overall FST among populations was approximately 0.28, but this large value resulted from one low-diversity population that had a large genetic distance to the other three populations (F(ST) = 0.10 without that population). There was no correlation between geographical and genetic distance among sites. Thus, the genetic structure of this species in China may be characterized by variable effective sizes and uneven movement among sites. We discuss the implications of this genetic structure for vaccine development and the spread of drug resistance in human hookworms, and compare the genetic structure of hookworms with that of other nematodes.

Animals↗
PubMed2001

The efficacy of the non-stress test in preventing fetal death in post-term pregnancy.

We conducted a case--control study to examine the efficacy of non-stress testing in preventing fetal death in post-term pregnancy. The analysis was based on data from the 1988 National Maternal and Infant Health Survey, which was a nationally representative sample of live births, fetal deaths and infant deaths that occurred in 1988. Information on whether a woman had non-stress testing was obtained from a questionnaire sent to prenatal care providers and hospitals. Cases were post-term women (with 42 weeks or more gestation) who had fetal deaths. Three post-term controls, who had live births and who delivered at the same time or later than the cases, were randomly chosen and individually matched to each case by maternal race. The proportion of women who had one or more non-stress tests during pregnancy was compared between cases and controls. Non-stress testing was used in 30.9% of the 126 cases and in 28.5% of the 375 controls. The race-adjusted odds ratio for exposure to non-stress test was 1.12 [95% CI 0.72, 1.75]. After controlling for other important confounding variables the odds ratio was 1.05 [95% CI 0.57, 1.91]. These results do not support the efficacy of non-stress testing in post-term pregnancies. A more detailed evaluation of this widely used screening procedure is needed.

Adult↗
PubMed2001

Can dietary factors explain differences in serum cholesterol profiles among different ethnic groups (Chinese, Malays and Indians) in Singapore?

In Singapore. there exists differences in risk factors for coronary heart disease among the three main ethnic groups: Chinese, Malays and Indians. This study aimed to investigate if differences in dietary intakes of fat, types of fat, cholesterol, fruits, vegetables and grain foods could explain the differences in serum cholesterol levels between the ethnic groups. A total of 2408 adult subjects (61.0% Chinese, 21.4% Malays and 17.6% Indians) were selected systematically from the subjects who took part in the National Health Survey in 1998. The design of the study was based on a cross-sectional study. A food frequency questionnaire was used to assess intakes of energy, total fat, saturated fat, polyunsaturated fat, monounsaturated fat, cholesterol, fruits, vegetables and cereal-based foods. The Hegsted score was calculated. Serum total cholesterol, low density lipoprotein cholesterol, high density lipoprotein cholesterol were analysed and the ratio of total cholesterol to high density lipoprotein cholesterol was computed. The results showed that on a group level (six sex-ethnic groups), Hegsted score, dietary intakes of fat, satutrated fat, cholesterol, vegetables and grain foods were found to be correlated to serum cholesterol levels. However, selected dietary factors did not explain the differences in serum cholesterol levels between ethnic groups when multivariate regression analysis was performed, with adjustment for age, body mass index, waist-hip ratio, cigarette smoking, occupation, education level and physical activity level. This cross-sectional study shows that while selected dietary factors are correlated to serum cholesterol at a group level, they do not explain the differences in serum cholesterol levels between ethnic groups independently of age, obesity, occupation, educational level and other lifestyle risk factors.

Adult↗
PubMed2001

Costs of managing Helicobacter pylori-infected ulcer patients after initial therapy.

BACKGROUND: The objective of this research was to evaluate the outcomes and costs of alternative approaches to managing patients previously treated for peptic ulcer disease and Helicobacter pylori infection. MATERIALS AND METHODS: A decision-analytic model was used to compare (1a) urease breath testing (UBT) for assessment of H. pylori status versus (1b) observation without further testing or treatment, among patients who were symptom-free following initial antimicrobial and antisecretory therapy for endoscopically demonstrated ulcer and H. pylori infection; and (2a) UBT versus (2b) repeat endoscopy with H. pylori testing, and versus (2c) repeat antimicrobial and antisecretory therapy without further testing, among patients who remained symptomatic following initial therapy. RESULTS: Among patients who were symptom free after initial therapy, 6.1% receiving UBT had symptomatic ulcer at one year, compared to 18.2% of those simply observed. The expected first-year cost per symptom-free patient following initial therapy was $591 for UBT compared to $480 for observation. Among patients with persistent symptoms after initial therapy, 21% receiving repeat therapy had symptomatic ulcer at one year, compared to 23.8% receiving repeat endoscopy, and 23.3% receiving UBT. Corresponding medical costs per patient were, respectively, $766, $1787 and $1122. CONCLUSIONS: The optimal approach to managing patients following initial treatment for ulcer and H. pylori infection depends on symptom status following initial therapy. For symptomatic patients, the preferred approach is to prescribe a repeat course of antimicrobial and antisecretory therapy. For patients without symptoms following initial therapy, UBT is the preferred approach because it is associated with a threefold lower risk of symptomatic ulcer at one year, although it costs an additional $110 per patient, compared with observation.

Breath Tests↗
PubMed2001

Apoptosis in adriamycin cardiomyopathy and its modulation by probucol.

The dose-dependent cardiomyopathy and heart failure due to adriamycin have been shown to be due to increased oxidative stress and loss of myocytes. We examined the incidence of myocardial apoptosis as well as changes in the expression of apoptotic regulatory gene products in an established animal model of adriamycin cardiomyopathy. Rats were treated with adriamycin (cumulative dose, 15 mg/kg), and the hearts were examined for apoptosis as well as expression of Bax, caspase 3, and Bcl-2 at 0, 4, 10, 16, and 21 days after the treatment. A significant increase in the incidence of apoptosis was seen at 4 days, followed by a decline at 10 and 16 days of posttreatment. At 21 days, the number of apoptotic cells increased again and included cells of the conducting system. Expression of Bax corresponded to these biphasic changes, whereas the converse was true for the expression of Bcl-2. The latter peaked at 10 days followed by a decline at 16 and 21 days. The Bax/Bcl-2 ratio also correlated with the incidence of apoptosis. Expression of caspase 3 correlated with increased apoptosis, but only at early time points. Probucol (cumulative dose, 120 mg/kg), a known antioxidant as well as promoter of endogenous antioxidants, significantly reduced the incidence of apoptosis as well as expression of Bax. Adriamycin-induced hemodynamic changes were also prevented by probucol. These data suggest that adriamycin-induced apoptosis is mediated by oxidative stress and may play a role in the development of heart failure.

Animals↗
PubMed2001

Human papillomavirus type 16 is an important infectious factor in the high incidence of esophageal cancer in Anyang area of China.

To investigate the potential role of human papillomavirus (HPV) infection in the pathogenesis of esophageal carcinomas in the Anyang area of China, we have evaluated specimens collected by balloon cytology examination from volunteers in two regions with significantly different incidences of esophageal carcinoma. 138 donors were from a village in a county with an esophageal carcinoma (EC) age-adjusted mortality rate of 132x10(5), the remaining 68 were resident in a second village from another county with an EC mortality rate of 52x10(5). Specimens were evaluated using both polymerase chain reaction (PCR) amplification and in situ hybridization (ISH) protocols. PCR results showed that the prevalence of the human papillomavirus type 16 (HPV-16) E6 gene in the high incidence area was 1.9-fold higher than that of the low incidence area (72 and 37%, respectively, P < 0.01). Moreover, the positive rate corresponded with pathology grade. Similar results were obtained with the HPV-16 E7 gene. As the cells undergoing cytopathological progress, the HPV-16 E6 positive rate was increased, in both villages. In contrast to HPV-16 E6 and E7, detection of the HPV L1 gene was consistently lower, and its prevalence decreased with increasing dysplasia grades (P < 0.05). By ISH analyses, the expression rate of HPV-16 E6 in the specimens collected from the high incidence area was 2.2-fold higher than those from the low incidence area (49 versus 22%, respectively; P < 0.05), and transcription of the E6 gene paralleled cytopathology. HPV-18 was also detected in 17 and 15% of the specimens from the high and low incidence areas, respectively, but most of these samples were also simultaneously HVP-16 positive. These results suggest that HVP-16 plays a causative role in the high incidence of esophageal cancer in the Anyang region of CHINA:

China↗
PubMed2001

Location of the platelet binding site in zymogen coagulation factor IX.

The assembly of the tenase complex on the surface of the platelet is an essential step in maintaining normal hemostasis as evidenced by the serious hemorrhagic diathesis associated with either factor IX (FIX) or factor VIII deficiencies. Understanding the regions and or residues of FIX crucial for proper binding to platelets has important clinical implications. The ability of FIX to bind activated platelets in the presence of 4 mmol/l CaCl2 was examined using electrophoretic light-scattering experiments. Wild-type FIX binds to activated platelets with dissociation constant Kd = 7.9 nmol/l. Activated FIX binds to activated platelets with Kd = 2 nmol/l. Activated factor VII does not bind activated platelets at physiological concentrations. The Gla domain of FIX is important for the binding of FIX to activated platelets since a chimera with a factor VII (FVII) template and FIX Gla [FVII(FIXGla)] has Kd = 9.6 nmol/l, and a chimera with a FVII template and FIX Gla, A and the first epidermal growth factor domain (EGF1) [FVII(FIXGla,A,EGF1)] has Kd = 9.7 nmol/l, but a chimera with a FIX template and a FVII Gla [FIX(FVIIGla)] does not bind activated platelets. Altering the fifth residue of FIX from a lysine to an alanine (Lys5<--Ala) abolishes the mutant from binding to collagen but does not affect FIX binding to the activated platelet (Kd = 9.8 nmol/l). Point mutations involved with residues 4 and 5 (Gly4<--Phe and Lys5<--no residue), residue 9 (Phe9<--Ala), residue 10 (Val10<--Lys) and residues 9-11 (Phe9<--Met, Val10<--Lys, Glu11<--Lys) do not bind to activated platelets.

Binding Sites↗
PubMed2001

Exposure rates of wrapped and unwrapped orbital implants following enucleation.

PURPOSE: To compare the complication rate of porous polyethylene orbital motility implants with solid acrylic implants following enucleation and identify possible risk factors. METHODS: The authors retrospectively reviewed the charts of a total of 117 consecutive enucleations performed at the University of Illinois at Chicago between March 28, 1994, and May 28, 1999. Data obtained included patient demographics, surgical indication, implant type, attending surgeon, surgical technique, and any reported complications. The primary outcome was presence or absence of implant exposure at the final recorded visit. RESULTS: Of the 117 identified cases, 29 were eliminated due to insufficient follow-up data. Of the 88 remaining cases, 48 patients received porous implants and 40 received solid acrylic implants. Implant exposure developed in four cases. All exposures occurred in unwrapped porous polyethylene implants (n=2) or porous polyethylene implants wrapped in absorbable material (n=2). All exposures occurred in patients younger than 18 years of age, and 75% occurred early after trauma-associated enucleation surgery. CONCLUSIONS: The exposure rate of porous polyethylene implants in this study (9%) was found to be comparable to published rates for hydroxyapatite implants. There were no exposures of unwrapped solid acrylic spheres. Unwrapped porous implants in pediatric patients or following trauma-related enucleation may represent an increased risk for postoperative implant exposure. Absorbable wrapping of porous implants may carry the same risk for exposure as no wrapping. Porous implants wrapped in durable material appear to be as safe as solid acrylic spheres.

Adolescent↗
PubMed2001

MDR1 pharmacogenetics: frequency of the C3435T mutation in exon 26 is significantly influenced by ethnicity.

P-glycoprotein (PGP), the product of the multidrug resistance gene (MDR1), acts as an energy-dependent efflux pump that exports its substrates out of the cell. PGP expression is an important factor regulating absorption of a wide variety of medications. It has also been associated with intrinsic and acquired cross resistance to a number of structurally unrelated anticancer drugs. A single nucleotide polymorphism (SNP) in exon 26 of the MDR1 gene, C3435T, was recently correlated with PGP protein levels and substrate uptake. Individuals homozygous for the T allele have more than four-fold lower PGP expression compared with CC individuals. As overexpression of PGP has been associated with altered drug absorption, therapy-resistant malignancies, and lower concentrations of HIV-1 protease inhibitors, this SNP may provide a useful approach to individualize therapy. To facilitate clinical application throughout the world, 1280 subjects from 10 different ethnic groups were evaluated for this SNP using the polymerase chain reaction-restriction fragment length polymorphism assay and the genotype and allele frequency for each group were ascertained. Marked differences in genotype and allele frequency were apparent between the African populations and the Caucasian/Asian populations (P < 0.0001). The Ghanaian, Kenyan, African American and Sudanese populations studied had frequencies of 83%, 83%, 84% and 73%, respectively, for the C allele. The British Caucasian, Portuguese, South-west Asian, Chinese, Filipino and Saudi populations had lower frequencies of the C allele compared to the African group (48%, 43%, 34%, 53%, 59%, and 55%, respectively). The high frequency of the C allele in the African group implies overexpression of PGP and may have important therapeutic and prognostic implications for use of PGP dependent drugs in individuals of African origin.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2001

Resistance studies with daptomycin.

We studied the in vitro emergence of resistance to daptomycin using three methods: spontaneous resistance incidence, serial passage in the presence of increasing drug concentrations, and chemical mutagenesis. No spontaneously resistant mutants were obtained for any organism tested (<10(-10) for Staphylococcus aureus, <10(-9) for Staphylococcus epidermidis, <10(-9) for Enterococcus faecalis, <10(-9) for Enterococcus faecium, <10(-8) for Streptococcus pneumoniae). Population analysis demonstrated that bacterial susceptibility to daptomycin is heterogeneous. Assay results were sensitive to calcium concentration and culture density, both of which can affect apparent resistance rates. Stable S. aureus mutants were isolated by both serial passage in liquid media and chemical mutagenesis. The daptomycin MICs for these isolates were 8- to 32-fold higher than for the parental strain. Many mutants with high MICs (>12.5 microg/ml) had significant growth defects but did not display phenotypes typical of S. aureus small colony variants. The voltage component (Delta psi) of the bacterial membrane potential was increased in three independent resistant isolates. In vivo data showed that some daptomycin-resistant mutants had lost significant virulence. For other mutants, the degree of in vitro resistance was greater than the change in in vivo susceptibility. These results suggest that infection with some daptomycin-resistant organisms may still be easily treatable.

Animals↗
PubMed2001

Different type 1 fimbrial genes and tropisms of commensal and potentially pathogenic Actinomyces spp. with different salivary acidic proline-rich protein and statherin ligand specificities.

Actinomyces spp. exhibit type 1 fimbria-mediated adhesion to salivary acidic proline-rich proteins (PRPs) and statherin ligands. Actinomyces spp. with different animal and tissue origins belong to three major adhesion types as relates to ligand specificity and type 1 fimbria genes. (i) In preferential acidic-PRP binding, strains of Actinomyces naeslundii genospecies 1 and 2 from human and monkey mouths displayed at least three ligand specificities characterized by preferential acidic-PRP binding. Slot blot DNA hybridization showed seven highly conserved type 1 fimbria genes (orf1- to -6 and fimP) in genospecies 1 and 2 strains, except that orf5 and orf3 were divergent in genospecies 1. (ii) In preferential statherin binding, oral Actinomyces viscosus strains of rat and hamster origin (and strain 19246 from a human case of actinomycosis) bound statherin preferentially. DNA hybridization and characterization of the type 1 fimbria genes from strain 19246 revealed a homologous gene cluster of four open reading frames (orfA to -C and fimP). Bioinformatics suggested sortase (orfB, orf4, and part of orf5), prepilin peptidase (orfC and orf6), fimbria subunit (fimP), and usher- and autotransporter-like (orfA and orf1 to -3) functions. Those gene regions corresponding to orf3 and orf5 were divergent, those corresponding to orf2, orf1, and fimP were moderately conserved, and those corresponding to orf4 and orf6 were highly conserved. Restriction fragment length polymorphism analyses using a fimP probe separated human and monkey and rat and hamster strains into phylogenetically different groups. (iii) In statherin-specific binding, strains of A. naeslundii genospecies 1 from septic and other human infections displayed a low-avidity binding to statherin. Only the orf4 and orf6 gene regions were highly conserved. Finally, rat saliva devoid of statherin bound bacterial strains avidly irrespective of ligand specificity, and specific antisera detected either type 1, type 2, or both types of fimbria on the investigated Actinomyces strains.

Actinomyces↗
PubMed2001

Virus-specific mRNA capping enzyme encoded by hepatitis E virus.

Hepatitis E virus (HEV), a positive-strand RNA virus, is an important causative agent of waterborne hepatitis. Expression of cDNA (encoding amino acids 1 to 979 of HEV nonstructural open reading frame 1) in insect cells resulted in synthesis of a 110-kDa protein (P110), a fraction of which was proteolytically processed to an 80-kDa protein. P110 was tightly bound to cytoplasmic membranes, from which it could be released by detergents. Immunopurified P110 catalyzed transfer of a methyl group from S-adenosylmethionine (AdoMet) to GTP and GDP to yield m(7)GTP or m(7)GDP. GMP, GpppG, and GpppA were poor substrates for the P110 methyltransferase. There was no evidence for further methylation of m(7)GTP when it was used as a substrate for the methyltransferase. P110 was also a guanylyltransferase, which formed a covalent complex, P110-m(7)GMP, in the presence of AdoMet and GTP, because radioactivity from both [alpha-(32)P]GTP and [(3)H-methyl]AdoMet was found in the covalent guanylate complex. Since both methyltransferase and guanylyltransferase reactions are strictly virus specific, they should offer optimal targets for development of antiviral drugs. Cap analogs such as m(7)GTP, m(7)GDP, et(2)m(7)GMP, and m(2)et(7)GMP inhibited the methyltransferase reaction. HEV P110 capping enzyme has similar properties to the methyltransferase and guanylyltransferase of alphavirus nsP1, tobacco mosaic virus P126, brome mosaic virus replicase protein 1a, and bamboo mosaic virus (a potexvirus) nonstructural protein, indicating there is a common evolutionary origin of these distantly related plant and animal virus families.

Cell Line↗
PubMed2001

Copper staining method for extracting biologically active proteins from native gels.

An attempt was made to make protein bands visible on native gel using copper staining, since such a mild staining procedure would make the entire native gel electrophoresis process non-denaturing. Copper staining not only was able to detect various proteins on native gel with reasonable sensitivity, but also made extraction and recovery of active proteins possible from the gel using a gentle procedure.

Chromatography, Gel↗