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Biomedical subjects

W Li

Publications and source records attributed to W Li.

At least 721 records · Page 40Linked to original sources

Partially folded conformations of inositol monophosphatase endowed with catalytic activity.

The stability of porcine brain inositol monophosphatase in the presence of increasing concentrations of urea was investigated at pH 7.5. Exposure of the enzyme to 8 M urea brings about the dissociation of the dimeric species of 58 kDa into monomeric forms as revealed by gel filtration chromatography. Unfolding of the protein by 8 M urea results in a decrease of the ellipticity at 220 nm (20%) together with a perturbation of the near-UV circular dichroism spectrum. Urea-treated inositol monophosphatase binds Co2+ ions with a dissociation constant of 3.3 microM. The enzyme is catalytically competent when assayed with 4-nitrophenyl-phosphate in the presence of the activating ion Co2+ at pH 7.5 in 8 M urea. The apparent activation constant for Co2+ is 2.5 mM. It is postulated that partially folded conformations of monomeric species preserve their catalytic function because the affinity of Co2+ ions for the metal coordination center of the protein is not perturbed by exposure to 8 M urea.

Animals↗

Identification of the gene responsible for Best macular dystrophy.

Best macular dystrophy (BMD), also known as vitelliform macular dystrophy (VMD2; OMIM 153700), is an autosomal dominant form of macular degeneration characterized by an abnormal accumulation of lipofuscin within and beneath the retinal pigment epithelium cells. In pursuit of the disease gene, we limited the minimum genetic region by recombination breakpoint analysis and mapped to this region a novel retina-specific gene (VMD2). Genetic mapping data, identification of five independent disease-specific mutations and expression studies provide evidence that mutations within the candidate gene are a cause of BMD. The 3' UTR of the candidate gene contains a region of antisense complementarity to the 3' UTR of the ferritin heavy-chain gene (FTH1), indicating the possibility of antisense interaction between VMD2 and FTH1 transcripts.

Amino Acid Sequence↗

Infective endocarditis in the grown-up congenital heart (GUCH) population.

AIMS: Infective endocarditis accounts for 4% of admissions to a specialized unit for grown-up congenital heart patients. This study defines lesions susceptible to infection, antecedent events, organisms, outcome and surgical treatment in a group of such patients. METHODS AND RESULTS: The grown-up congenital heart disease database was searched for all patients aged 13 years and above with adequate documentation of infective endocarditis retrospectively between 1983-1993 and thereafter between 1993-1996. There were 185 patients (214 episodes) divided into Group I: 128 patients unoperated or palliated and Group II: 57 patients after definitive repair and/or valve repair/replacement. In Group I, the commonest affected sites were ventricular septal defect in 31 (24%), left ventricular outflow tract in 22 (17%) and mitral valve in 17 (13%) and in Group II, left ventricular outflow tract in 20 (35%), repaired Fallot in 11 (19%), and atrioventricular defects in eight (14%). Infective endocarditis was not seen in secundum atrial septal defects before or after closure; in closed ventricular septal defects and ducts without left-sided valve abnormality; in isolated pulmonary stenosis; in unrepaired Ebstein: or after Fontan-type or Mustard operations. Surgery was performed in 39 patients: as an emergency in 17, and for failed medical therapy in 22. Only 87 (41%) of patients had a predisposing event: dental procedure or sepsis were the commonest events in Group I (33%) and cardiac surgery in Group II (50%). Streptococci species were found in 54% of Group I patients and in 45% of Group II. Staphylococci aureus was commoner in Group II (25%) compared to Group I (14%). Mean time from the onset of symptoms to diagnosis was 60 and 29 days in Groups I and II, respectively. Eight (4%) patients died as a result of septicaemia related to emergency or repeated surgery and Staphylococcus aureus infection. Recurrent attacks occurred in 21 (11%) patients. CONCLUSION: Reparative surgery does not prevent endocarditis except for closure of a ventricular septal defect and duct. Delay in diagnosis is serious since it contributes to mortality, although the overall mortality % is not high. Specific lesions are not affected so prophylaxis is probably unnecessary in those anomalies.

Adolescent↗

Antimicrobial flavonoids from Glycyrrhiza glabra hairy root cultures.

A new compound named licoagrodione was isolated from the hairy root cultures of Glycyrrhiza glabra (Fabaceae) together with five known prenylated flavonoids. The structure of licoagrodione has been elucidated on the basis of spectral evidence and it was found to have antimicrobial activity indicated by disc diffusion method.

Anti-Bacterial Agents↗

Change in visually perceived eye level without change in perceived pitch.

Both the physical elevation that appears to correspond to eye level and the visually perceived pitch of a visual field are linear functions of the physical pitch of a normally illuminated, complexly structured visual field. One of the possible bases for the large effect of physical pitch on the elevation of visually perceived eye level (VPEL) is that the visual field generates a mental representation which specifies spatial coordinates and these determine the VPEL elevation ('implicit-surface model'; ISM). The influence on the elevation of VPEL is nearly as large when the visual field contains either one or two long pitched-from-vertical or rolled-from-vertical lines in otherwise total darkness as when it consists of a well-illuminated and complexly structured pitched room (L Matin and W Li, 1994 Vision Research 34 311-330), and, in order to examine the ISM, we employed a rolled-from-vertical, two-line configuration within a frontoparallel plane viewed in otherwise total darkness. Measurements of visually perceived pitch were made by a manual matching procedure and VPEL measurements were made by the psychophysical setting of the elevation of a small visual target to appear at eye level while each of three subjects viewed the two-line configuration at each of three horizontal eccentricities with the configuration at each of seven roll orientations. In direct contradiction to the ISM, the perceived pitch of the two-line configuration did not deviate significantly from the erect orientation ('vertical') for any roll at any eccentricity, but the elevation of VPEL changed systematically with the roll of the configuration both at left and at right eccentricities, and did not change at all with the two-line configuration centered on the median plane. Consistent with our previous work and with our previous interpretation regarding the basis for VPEL (L Matin and W Li, 1994 Vision Research 34 2577-2598), the variation of VPEL for the two-line visual field equals the average of the VPEL variations produced by viewing each of the single lines separately.

Humans↗

A new saponin from the leaves and stems of Panax quinquefolium L. collected in Canada.

A new dammarane-type saponin named quinquenoside L3 (1) together with vina-ginsenoside R3 (2) were isolated from the leaves and stems of Panax quinquefolium L. collected in Canada. On the basis of physicochemical and spectral evidences, 1 was established as 3-O-beta-D-glucopyranosyl-20-O-[beta-D-xylopyranosyl-(1-->6)-beta-D -glucopyranosyl] 20(S)-dammar-23-ene-3 beta, 12 beta,20,25-tetryol.

Carbohydrate Conformation↗

OxLDL-induced macrophage cytotoxicity is mediated by lysosomal rupture and modified by intralysosomal redox-active iron.

Oxidized low density lipoprotein (oxLDL) is believed to play a central role in atherogenesis. LDL is oxidized in the arterial intima by mechanisms that are still only partially understood. OxLDL is then taken up by macrophages through scavenger receptor-mediated endocytosis, which then leads to cellular damage, including apoptosis. The complex mechanisms by which oxLDL induces cell injury are mostly unknown. This study has demonstrated that oxLDL-induced damage of macrophages is associated with iron-mediated intralysosomal oxidative reactions, which cause partial lysosomal rupture and ensuing apoptosis. This series of events can be prevented by pre-exposing cells to the iron-chelator, desferrioxamine (DFO), whereas it is augmented by pretreating the cells with a low molecular weight iron complex. Since both DFO and the iron complex would be taken up by endocytosis, and thus directed to the lysosomal compartment, the results suggest that the normal contents of lysosomal low molecular weight iron may play an important role in oxLDL-induced cell damage, presumably by catalyzing intralysosomal fragmentation of lipid peroxides and the formation of toxic aldehydes and oxygen-centered radicals.

Animals↗

A novel method for selection of chymotrypsin inhibitors from a phage peptide library.

A novel screening strategy has been developed for the identification of alpha-chymotrypsin inhibitors from a phage peptide library. In this strategy, the standard affinity selection protocol was modified by adding a proteolytic cleavage period to avoid recovery of alpha-chymotrypsin substrates. After four cycles of selection and further activity assay, a group of related peptides were identified by DNA sequencing. These peptides share a consensus sequence motif as (S/T)RVPR(R/H). Then, a corresponding short peptide (Ac-ASRVPRRG-NH2) was synthesized chemically and proved to be an inhibitor of alpha-chymotrypsin. The present work provides a useful way for searching proteinase inhibitors without detailed knowledge of the molecular structure.

Bacteriophages↗

Chemokine receptors and the molecular basis for human immunodeficiency virus type 1 entry into peripheral hematopoietic stem cells and their progeny.

There exist at least two major coreceptors for human immunodeficiency virus (HIV)-1 entry into target cells, the CXCR-4 and CCR-5 chemokine receptors for T lymphocyte-tropic and macrophage-tropic strains of HIV-1, respectively. Highly purified human CD34 cells derived from umbilical cord blood were shown not to express CD4, CXCR-4, and CCR-5 on their cell membranes, as analyzed by immunofluorescent staining and flow cytometric analyses. However, expression of these molecules was inducible when highly purified CD34 cells underwent proliferation and differentiation along myeloid cell lineages, in the presence of suitable cocktails of hematopoietic growth factors. HIV-1 infectivity studies showed that macrophage-tropic strains of HIV-1 could efficiently infect differentiated CD34 cells. T lymphocyte-tropic strains could not infect CD34 cells before or after induction of receptors and coreceptors. These data suggest that HIV-1 infection of CD34 cells and their progeny depends on membrane expression of the critical CD4 receptor, as well as certain chemokine coreceptors.

Antigens, CD↗

Ganciclovir susceptibilities and analysis of UL97 region in cytomegalovirus (CMV) isolates from bone marrow recipients with CMV disease after antiviral prophylaxis.

Ganciclovir susceptibilities and UL97 sequences were analyzed in 20 cytomegalovirus (CMV) isolates recovered from 15 bone marrow transplant recipients with active CMV infection after prophylaxis with acyclovir (group I; 12 isolates) or after acyclovir prophylaxis followed by ganciclovir therapy (group II; 8 isolates). All group I isolates were susceptible to ganciclovir. Five group II isolates were susceptible to ganciclovir, and 3 isolates (all from the same person) were resistant to ganciclovir (IC50 > 12 microM). Ganciclovir resistance UL97 mutations were found in 4 group II isolates, including a ganciclovir-susceptible isolate obtained from 1 patient after 41 days of therapy with ganciclovir and 3 ganciclovir-resistant isolates obtained from another patient after 73, 116, and 132 days of treatment with ganciclovir. Ganciclovir-resistant CMV isolates may emerge rapidly in bone marrow transplant recipients who are treated with ganciclovir after receiving prophylaxis with acyclovir.

Acyclovir↗

Assessing hepatitis A virus epidemic stochastic process in eight cities in China in 1990.

BACKGROUND: In The People's Republic of China in 1990, the age-specific seroprevalence of hepatitis A was investigated in eight large cities. METHODS: A stochastic model, the two-state Markov chain, was applied to hepatitis A virus seroprevalence data by age group. An age-specific risk rate, Markov Risk Rate (MRR), and its weighted sum, Total MRR, are defined and used as novel measure indices to prioritize age groups for allocating vaccine or to decide in which cities vaccine should be used to prevent hepatitis A. RESULTS: In 1990, the MRR1- in Xi'an, Jinan, Ha'erbin and Huhehaote, and the MRR10- in Chongqing were over 40. The MRR10- in Xi'an, Nanjing, Jinan and Ha'erbin and the MRR20- in Chongqing and Nanjing were over 20. The Total MRR in Chongqing and Ha'erbin were over 160, which was higher than the warning value. CONCLUSIONS: All age groups whose MRR was over 20 are strongly recommended to be vaccinated first. Chongqing and Ha'erbin are cities at high risk of a hepatitis A virus epidemic in the 1990s and therefore should be under close surveillance.

Adolescent↗

Deposition of charged particles on lung airways.

The effect of a single electric charge on the efficiency with which ultrafine particles deposit in human airways has been investigated. When inhaled short-lived radon progeny are attached to electrically neutral particles their deposition efficiency is controlled by diffusion. But most ambient particles carry one, or a few, charges. We measured and compared the deposition (DE) of singly charged, charge-neutralized, and zero-charge 20-nm and 125-nm particles in hollow-cast models of human airways. These particle sizes were selected because they are about where modal peaks occur for the activity of the short-lived radon progeny in indoor air. For singly charged 20-nm particles deposition (+/- standard error) in the casts was 3.4 +/- 0.3 times that for charge neutralized aerosols and 5.3 +/- 0.3 times the amount deposited for zero-charged particles. Corresponding ratios for the 125-nm particles were 2.3 +/- 0.3 and 6.2 +/- 0.7. Since most ambient particles are charged this effect must be considered when models are used to predict dose from inhaled ultrafine particles.

Adult↗

Chronic relapsing experimental autoimmune encephalomyelitis: effects of insulin-like growth factor-I treatment on clinical deficits, lesion severity, glial responses, and blood brain barrier defects.

Chronic relapsing experimental autoimmune encephalomyelitis (crEAE), a model for multiple sclerosis, was used to test 2 regimens of insulin-like growth factor-I (IGF-I) treatment. We induced crEAE by injecting 3x10(7) myelin basic protein-(MBP) sensitized lymph node cells into adult female SJL/J mice. Fifty-one mice, divided randomly into 4 groups, were used in the first trial. Two groups received IGF-I (a gift of Cephalon, Inc.) 0.6 mg/kg/d subcutaneously from day 7 to day 16 and the other two groups received placebo injections. IGF-I treatment reduced clinical deficits during the first attack and during 2 subsequent relapses. Image analysis of immunostained and histological sections showed that IGF-I treatment reduced BBB defects and both the numbers and sizes of inflammatory, demyelinating, and demyelinated lesions. Twelve mice that had recovered from their first attack were used in our second trial to evaluate possible adverse effects of prolonged treatment with a higher dose of IGF-I. Six received 1.2 mg/kg/d for 6 weeks (days 19-63). No adverse effects of IGF-I treatment were identified. The eyes, hearts, livers, and kidneys of IGF-I-treated mice were normal histologically and their spleens also appeared normal except for mild to moderate microscopic increases in lymphopoesis. Our results suggest that prolonged IGF-I treatment is well tolerated and that the anti-inflammatory effects of IGF-I have a major role in reducing clinical deficits and lesion severity in crEAE. These effects, if present in multiple sclerosis, may benefit patients with this disease.

Animals↗

Compositional heterogeneity within, and uniformity between, DNA sequences of yeast chromosomes.

The heterogeneity within, and similarities between, yeast chromosomes are studied. For the former, we show by the size distribution of domains, coding density, size distribution of open reading frames, spatial power spectra, and deviation from binomial distribution for C + G% in large moving windows that there is a strong deviation of the yeast sequences from random sequences. For the latter, not only do we graphically illustrate the similarity for the above mentioned statistics, but we also carry out a rigorous analysis of variance (ANOVA) test. The hypothesis that all yeast chromosomes are similar cannot be rejected by this test. We examine the two possible explanations of this interchromosomal uniformity: a common origin, such as genome-wide duplication (polyploidization), and a concerted evolutionary process.

Analysis of Variance↗

Guidance of intracoronary radiation therapy based on dose-volume histograms derived from quantitative intravascular ultrasound.

Application of ionizing radiation to prevent restenosis in atherosclerotic vessels treated by balloon angioplasty is a new treatment under investigation in interventional cardiology and radiology. There is variability in dose prescription, and both gamma- and beta-emitters are used, leading to a wide range of dose distribution over the arterial vessel wall. We present a new modality of dosimetry based on a method that three-dimensional (3-D) image reconstruction of electrocardiogram (ECG)-gated intravascular ultrasound (IVUS) images. Dose volume histograms (DVH) are used to describe the cumulative distribution of dose over two specific volumes: i) at the level of the luminal surface, defined with a thickness of 0.1 mm from the automatically detected contour of the highly echogenic blood-vessel interface, and ii) the adventitia volume is computed considering a 0.5-mm thickness from the echogenic media-adventitia interface. DVH provide a tool for reporting the actual delivered dose at the site believed to be the target: the adventitia, and to detect excessive radiation which could lead to vascular complications. Simulation of a gamma-emitter or of a radioactive source train in the center of the lumen are possible. The data obtained from the first ten patients included in the beta-irradiation trial (BERT 1.5) conducted in our institution are presented, supporting the use of DVH based on quantitative IVUS measurements for optimal dose prescription in vascular interventional radiation therapy.

Brachytherapy↗

Purification and sequencing of a 21 kDa and 25 kDa bovine enamel metalloproteinase.

The developing enamel matrix contains metalloproteinases that are presumed to have a role in hydrolysis of enamel matrix proteins. Determination of the identity and function of these proteinases requires further information such as their amino acid composition and sequence. In this study, we purified the 21 kDa and 25 kDa matrix metalloproteinase from secretory stage bovine enamel matrix. After extraction, these proteinases were further purified by sequential separation by ion exchange, Con A affinity chromatography, and reversed phase HPLC. The proteinases were separated by SDS PAGE, transferred to a PVDF membrane and the N-terminus was sequenced. The N-terminal sequences of both proteinases were the same, and showed homology to the porcine enamelysin (MMP 20) cDNA sequence. A cDNA for bovine MMP 20 was isolated from a bovine enamel organ cDNA library using a probe generated by PCR amplification. The coding regions of bovine and porcine MMP 20 cDNAs were highly homologous and contained the same regions of predicted amino acid sequence homology with the proteinase N-terminal sequences. These results suggest that the 21 kDa and 25 kDa enamel matrix metalloproteinases are cleavage products of the initially secreted MMP 20, and that the sequence for MMP 20 is conserved across species.

Amino Acid Sequence↗

Time-dependent effects of Klebsiella pneumoniae endotoxin on hepatic drug-metabolizing enzyme activity in rats.

The time-dependent effects of Klebsiella pneumoniae endotoxin on hepatic cytochrome P450-dependent drug-metabolizing capacity (cytochrome P450 and b5 content, activity of aminopyrine N-demethylase, p-nitroanisole O-demethylase, aniline hydroxylase and benzphetamine N-demethylase) and on the pharmacokinetics of antipyrine have been determined in rats. Measurement of enzyme activity and antipyrine (after intravenous injection of 20 mg kg(-1)) were performed 2, 24 and 96 h after a single intraperitoneal injection of endotoxin (1 mg kg(-1)) and after repeated doses (once daily for 4 days). The contribution of tumour necrosis factor alpha (TNFalpha) to the endotoxin-induced changes was also examined in rats pretreated with granulocyte colony-stimulating factor (G-CSF). The systemic clearance of antipyrine and the activity of hepatic cytochrome P450-dependent drug-metabolizing enzymes were dramatically reduced 24 h after a single injection of endotoxin, but had returned to control levels by 96h. The magnitudes of these decreases in these measurements after repeated doses of endotoxin were similar to those seen 24h after the single dose. The systemic clearance of antipyrine correlated significantly with cytochrome P450 content and aminopyrine N-demethylase activity. In histopathological experiments, moderate hypertrophy of Kupffer cells was observed, with no evidence of severe liver-tissue damage. G-CSF pretreatment suppressed the increased plasma concentrations of TNFalpha produced 2 h after single endotoxin injection, but did not eliminate the endotoxin-induced decrease in the systemic clearance of antipyrine, suggesting that TNFalpha is not the sole component responsible for the reduction of cytochrome P450-mediated drug-metabolizing enzyme activity. These results provide evidence that a single intraperitoneal injection of 1.0 mgkg(-1)K. pneumoniae endotoxin in rats reduces hepatic P450 and b5 levels, and reduces the activity of various cytochrome P450-mediated drug-metabolizing enzymes without causing severe liver-tissue damage. This suggests that the effect of endotoxin on hepatic cytochrome P450-mediated drug-metabolizing isozymes is non-selective.

Animals↗

[Antibody response to a single injection of influenza vaccine among geriatric inpatients vaccinated annually].

To determine the efficacy of a single influenza vaccine administration in the elderly receiving annual influenza vaccination, antibody response to influenza vaccine was compared between once and twice injections in a geriatric cohort. Influenza vaccination had been done for 69 inpatients in the year prior to the study, and was administered twice for 34 of them and once for the other 35 during the study period. Influenza vaccine was injected twice to 77 inpatients who had not received influenza vaccine in the year prior to the study. Hemoagglutination inhibition (HI) antibody titer for influenza A/H1N1, A/H3N2, and B was measured before vaccination, after the first vaccination, after the second vaccination, and after the epidemic period, September 1995 to April 1996. HI antibody titer prior to vaccination was significantly higher in the patients who had received influenza vaccination the previous year. The influenza vaccine induced an increase in HI titer in almost all subjects, and the geometric mean of the HI titer after vaccination in the patients who received vaccine once was comparable to that of the patients injected vaccine twice. The number of patients with HI titers of over 128x increased, and the frequency ranged from 60.0% to 97.1% for the influenza viruses of the three subtypes. The frequency of HI titers over 128x was not significantly different among the three groups. The second vaccination did not increase the number of patients with HI titers over 128x when compared with the number after the first injection in the patients who had received influenza vaccine the previous year. These results suggest that prior vaccination does not diminish the antibody response to influenza vaccine in the elderly. The efficacy of a single influenza vaccination is comparable to that achieved by twice injections in the elderly receiving annual influenza vaccination.

Aged↗