Search PubMed⌕ Search

Biomedical subjects

S Chen

Publications and source records attributed to S Chen.

At least 559 records · Page 31Linked to original sources
PubMed1999

Tetrameric short tandem repeat (STR) system D15S233 (wg1d1): sequencing and frequency data in the japanese and Chinese populations.

We evaluated the forensic usefulness of D15S233 (wg1d1), a tetrameric short tandem repeat (STR) locus, in the Japanese and Chinese populations. Typing was performed by denaturing polyacrylamide gel electrophoresis followed by silver staining. Nine different alleles were found in 472 Japanese chromosomes and seven in 186 Chinese chromosomes. 102 alleles sequenced were composed of two kinds of repeats (AGGA and GGGA). All alleles differed in size by one tetranucleotide repeat unit, and no insertion or deletion was found. The expected unbiased heterozygosities in Japanese and Chinese were 0.766 and 0.785, respectively. No significant deviations from the Hardy-Weinberg equilibrium were found in either population. We retyped all samples using an alternative pair of flanking primers in order to detect any spurious appearances of homozygotes due to sequence variation at the primer annealing site. One heterozygous sample had unbalanced density bands when the original primer set was used, but equal density bands when our newly designed primer set was used. Sequencing analysis revealed that the sparser allele had one nucleotide substitution near the 5' end of the annealing site of the original primer region. Thus, all apparently homo/heterozygous samples were thought to be truly homo/heterozygous. We also applied the D15S233 locus to paternity testing and forensic identification. Our results suggest that this locus should be a very useful STR locus for forensic practice in Japanese and Chinese.

Journal Article↗
PubMed1999

Dying-back of Purkinje cell dendrites with synapse loss in aging rats.

Qualitative and quantitative changes were found in the cerebellar circuitry of old as compared to young rats. The old group had a reduced number of synapses (at least 30%), however, there was an increase in the size of remaining synaptic components (13.5% for spine head volume, 66% for bouton volume, and 17% for the area of synaptic contact zones). Furthermore, there were pronounced morphological changes in the older group appearing as: 1) prominent lipofuscin bodies in Purkinje cell somata, 2) numerous myelinated fibers in the lower part of the molecular layer, 3) tortuous Purkinje cell dendrites in a thinned molecular layer, and 4) abundant vacuolar profiles and membrane swirls in small and intermediate-sized dendrites. Our findings suggest that Purkinje cell dendrites are dying-back reducing the target field for granule cells and that remaining synaptic sites compensate by increasing synaptic contact area as well as the size of pre- and postsynaptic structures.

Aging↗
PubMed1999

The impact of attitudes on memory: an affair to remember.

Many theories of the effects of attitudes on memory for attitude-relevant information would predict that attitudinally congenial information should be more memorable than uncongenial information. Yet, this meta-analysis showed that this congeniality effect is inconsistent across the experiments in this research literature and small when these effects are aggregated. The tendency of the congeniality effect to decrease over the years spanned by this literature appeared to reflect the weaker methods used in the earlier studies. The effect was stronger in 2 kinds of earlier experiments that may be tinged with artifact: those in which the coding of recall measures was not known to be blind and those that used recognition measures that were not corrected for bias. Nonetheless, several additional characteristics of the studies moderated the congeniality effect and suggested that both attitude structure and motivation to process attitude-relevant information are relevant to understanding the conditions under which people have superior memory for attitudinally congenial or uncongenial information.

Attitude↗
PubMed1999

Protection of human breast cancer cells from complement-mediated lysis by expression of heterologous CD59.

CD59, decay accelerating factor (DAF) and membrane cofactor protein (MCP) are widely expressed cell surface glycoproteins that protect host cells from the effects of homologous complement attack. Complement inhibitory activity of these proteins is species-selective. We show that the human breast cancer cell line MCF7 is relatively resistant to lysis by human complement, but is effectively lysed by rat or mouse complement. CD59, DAF and MCP were all shown to be expressed by MCF7. The species-selective nature of CD59 activity was used to demonstrate directly the effectiveness of CD59 at protecting cancer cells from complement-mediated lysis. cDNAs encoding rat and mouse CD59 were separately transfected into MCF7 cells, and cell populations expressing high levels of the rodent CD59 were isolated by cell sorting. Data show that rat and mouse CD59 were highly effective at protecting transfected MCF7 cells from lysis by rat and mouse complement, respectively. Data further reveal that rat CD59 is not effective against mouse complement, whereas mouse CD59 is effective against both mouse and rat complement. These studies establish a model system for relevant in vivo studies aimed at determining the effect of complement regulation on tumourigenesis, and show that for effective immunotherapy using complement-activating anti-tumour antibodies, the neutralization of CD59 and/or other complement inhibitory molecules will probably be required.

Animals↗
PubMed1999

Transmission electron microscopy of interfaces in structural ceramic composites

Ceramic composites based either on a particulate, fibre or a lamellar architecture are potentially useful as damage-tolerant high-temperature engineering materials. The ability of the interfaces in such systems to deflect cracks is vital to the damage tolerance of these materials. Transmission electron microscopy techniques enable the chemical and physical characterization of these interfaces, providing information on interlayer thicknesses, chemical species, local bonding and the microstructural features which give rise to the interfacial properties, thereby enabling a full understanding not only of composites after processing, but also after exposure to aggressive environments such as air at high temperature. Examples of the application of transmission electron microscopy to all three composite architectures are described.

Journal Article↗
PubMed1999

Biosynthesis of ansatrienin (mycotrienin) and naphthomycin. Identification and analysis of two separate biosynthetic gene clusters in Streptomyces collinus Tü 1892.

The polyketide chains of the two ansamycin antibiotics, ansatrienin (mycotrienin) and naphthomycin produced by Streptomyces collinus are assembled using 3-amino-5-hydroxybenzoic acid (AHBA) as a starter unit. The gene encoding AHBA synthase, an enzyme which catalyzes the final step of AHBA biosynthesis in the recently discovered aminoshikimate pathway, has been used to identify two separate antibiotic biosynthetic gene clusters in S. collinus. In one of these clusters, analysis of approximately 20 kb of contiguous sequence has revealed both a cluster of six genes presumed to play a role in the AHBA pathway and the beginning of a polyketide synthase (PKS) gene containing an acyl ACP ligase domain. This domain is likely responsible for loading AHBA onto the PKS. This gene cluster also contains chcA, encoding the enzyme 1-cyclohexenylcarbonyl CoA reductase, which is essential for the biosynthesis of the cyclohexanecarboxylic acid moiety of ansatrienin from shikimic acid, and a peptide synthetase. This gene cluster thus seems to control the biosynthesis of ansatrienin, which contains a side chain of N-cyclohexanecarbonyl-d-alanine esterified to the macrocyclic lactam backbone. In the putative naphthomycin biosynthetic gene cluster approximately 13 kb of contiguous sequence has revealed a second set of the genes required for AHBA biosynthesis. In addition the end of a polyketide synthase and a gene putatively involved in termination of the chain extension process, formation of an intramolecular amide bond between the AHBA nitrogen and the carboxyl group of the fully extended polyketide chain, have been identified. Thus, despite commonality in biosynthesis, the ansatrienin and naphthomycin biosynthetic gene clusters show clear organizational differences and carry separate sets of genes for AHBA biosynthesis.

Anti-Bacterial Agents↗
PubMed1999

Prevention of crescentic glomerulonephritis by immunoneutralization of the fractalkine receptor CX3CR1 rapid communication.

BACKGROUND: Fractalkine is a newly identified T-cell and monocyte/macrophage (Mphi) chemokine with a transmembrane domain and is a cell-surface protein on activated endothelium. It can mediate adhesion of cells expressing the fractalkine receptor CX3CR1. These unique features make fractalkine well suited for leukocyte recruitment in tissues with high blood flow as in the renal glomerulus. METHODS: Fractalkine expression in glomeruli and response of isolated glomerular inflammatory cells to fractalkine were studied in the Wistar-Kyoto (WKY) crescentic glomerulonephritis model. Antibody was used to confirm the proinflammatory role of fractalkine. RESULTS: Fractalkine was markedly induced in the endothelium of nephritic rat glomeruli, and inflammatory leukocytes infiltrating the glomeruli expressed increased levels of CX3CR1. Anti-CX3CR1 antibody treatment dramatically blocked leukocyte infiltration in the glomeruli, prevented crescent formation, and improved renal function. CONCLUSIONS: Fractalkine plays a central role in leukocyte trafficking at the endothelium in the high-flow glomerular circuit and, in turn, implicates CX3CR1 as a prime drug target for therapeutic intervention of endothelium-related inflammatory diseases.

Animals↗
PubMed1999

Protective effects of ischemic preconditioning on lung ischemia reperfusion injury: an in-vivo rabbit study.

BACKGROUND: The goal of this study was to determine the effect of ischemic preconditioning on the extent of normothermic lung ischemia reperfusion injury in rabbits in vivo. METHODS: Thirty male Japanese white rabbits were randomized into two groups. Fifteen rabbits were treated with ischemic preconditioning (their left lung hilus clamped for 10 minutes and released for 15 minutes (group IP)). Fifteen rabbits were not treated with ischemic preconditioning (group C). Then the left lung hilus of both groups were occluded for 60 minutes and reperfused for 60 minutes. Mean arterial pressure, mean pulmonary artery pressure, and core temperature were recorded. Femoral artery blood samples and lung tissue samples were collected after ischemic preconditioning and after 60 minutes of reperfusion. RESULTS: The lung tissue showed little injury after ischemic preconditioning. After 60 minutes of reperfusion, the angiotensin II (A II) and arterial oxygen tension (PaO2) levels in group IP were significantly higher than those in group C, mean pulmonary artery pressure in group IP was significantly lower than that in group C, the wet/dry ratio and malondialdehyde content of lung tissue in group IP was significantly lower than that in group C, the superoxide dismutase contents of lung tissue in group IP was significantly higher than that in group C, and histological findings showed less damage in group IP than in group C. CONCLUSION: Lung ischemic preconditioning could reduce normothermic rabbit lung ischemia-reperfusion injury. The possible mechanisms are increased production of endogenous A II and reduced formation of oxygen free radicals during lung ischemia for 60 minutes followed by reperfusion for 60 minutes.

Angiotensin II↗
PubMed1999

Responses in the absorptive phase in muscle and liver protein synthesis rates of growing rats.

The effect of time after beginning of a meal (30, 60, 90 and 120 min) on liver and gastrocnemius muscle protein synthesis was tested in growing male rats using the large dose technique, based on a 10 min exposure to [15N]phenylalanine. The fractional synthesis rate was estimated from the ratio between the atom percent excess of tissue protein-bound and free labelled phenylalanine. The latter was measured by gas chromatography mass spectrometry using the tertiary-butyldimethylsilyl amino acid derivatives. The protein-bound phenylalanine of gastrocnemius muscle was separated from the other amino acids using preparative amino acid chromatography and then oxidised to N2 in an automated carbon-nitrogen Roboprep (CN) combustion module attached to a continuous flow isotope ratio mass spectrometer (IRMS), with m/z ions 28 and 29 monitored. The protein-bound phenylalanine from liver was separated by a gas chromatograph attached to a sample preparation module and an isotope ratio mass spectrometer (GC C-IRMS), with again m/z ions of 28 and 29 monitored. The following results were obtained: the daily fractional protein synthesis rates (ks) in gastrocnemius muscle and liver were 13.9% and 65.6% respectively, in 12 h fasted 145 g rats. These ks increased within 30 min after ingestion of meal to 14.9% and 91.8% for muscle and liver, respectively, and remained at these values for the next 90 min (14.6% and 87.4% at 60 min, and 14.3% and 88.6% at 120 min after the beginning of feeding). It was concluded that measurement of protein synthesis rates characteristics for the absorptive phase can be undertaken in a period from thirty minutes to two hours after start of a meal, without significant changes in the ks values.

Amino Acids↗
PubMed1999

Rheological characterization of hydroxypropylcellulose gels.

The present paper describes the rheological properties of hydroxypropylcellulose (HPC) gels formulated in propylene glycol (PG), water, ethanol, and mixtures of these components. The effects of molecular weight, polymer concentration, and solvent composition on the apparent viscosity and flow characteristics have been studied by continuous shear rheometry. The HPC gels are shear thinning and do not exhibit significant yield or hysteresis in their rheograms. The apparent viscosity increases with increasing molecular weight and concentration of the polymer, as expected. Although not so pronounced at lower concentrations (< or = 1.5%), HPC gels tend to become increasingly non-Newtonian with increasing molecular weight at higher polymer concentrations (3%). A mathematical model has been proposed for the prediction of viscosities of HPC gels. There exists a high degree of dependence on molecular interactions between various solvent molecules in the prediction of mixture viscosities in ternary systems. The effects of solvent composition on the viscoelastic behavior of these gels have also been examined by dynamic mechanical analysis. The HPC gels are highly viscoelastic and exhibit greater degrees of elasticity with increased PG content in ternary solvent mixtures with water and ethanol. The study also suggests that dynamic mechanical analysis could prove to be a useful tool in the determination of zero-shear viscosities, viscosities that are representative of most realistic situations.

Cellulose↗
PubMed1999

Leber congenital amaurosis caused by a homozygous mutation (R90W) in the homeodomain of the retinal transcription factor CRX: direct evidence for the involvement of CRX in the development of photoreceptor function.

The CRX (cone-rod homeobox) gene is specifically expressed in developing and mature photoreceptors and encodes an otd/Otx-like paired homeodomain protein. Mutant alleles of the CRX gene have recently been associated with autosomal dominant cone-rod dystrophy (CORD) as well as dominant Leber congenital amaurosis (LCA). Since LCA is more commonly inherited in an autosomal recessive manner, we examined a cohort of recessive LCA patients for CRX mutations. A homozygous substitution of arginine (R) at codon 90 by tryptophan (W) was identified in the CRX homeodomain of one of the probands who was nearly blind from birth. A group of 48 control individuals and 190 previously characterized CORD probands did not reveal this sequence change. The mutant CRXR90W homeodomain demonstrated decreased binding to the previously identified cis sequence elements in the rhodopsin promoter. In transient transfection experiments, the mutant protein showed significantly reduced ability to transactivate the rhodopsin promoter, as well as lower synergistic activation with the bZIP transcription factor NRL. Heterozygosity of the mutant CRX (R90W) allele was detected in both parents and in an older sibling. Ophthalmologic examination and electro-retinography revealed a subtle abnormality of cone function in both the parents. These data suggest that the R90W mutation results in a CRX protein with reduced DNA binding and transcriptional regulatory activity and that the subsequent changes in photoreceptor gene expression lead to the very early onset severe visual impairment in LCA.

Adolescent↗
PubMed1999

Functional dissection of the promoter of the interphotoreceptor retinoid-binding protein gene: the cone-rod-homeobox element is essential for photoreceptor-specific expression in vivo.

The essential control elements in the interphotoreceptor retinoid-binding protein gene (IRBP) promoter are located between -156 and +19. The -156/-109 sequence contains a retina-specific DNAse I footprint and shows a positive regulatory activity in transiently transfected retinoblastoma cells. The -105/-85 sequence is G/C rich, shows a non-tissue specific DNAse I hypersensitivity, and a negative regulatory activity in retinoblastoma cells. The -76/-42 sequence shows a retinal-specific footprint and contains a "cone-rod-homeobox element" (CRXE) and a "photoreceptor conserved element" (PCE). IRBP promoter fragments with mutations in either CRXE, PCE or in both were linked to reporter genes and analyzed both by transient transfection and in transgenic mice. In retinoblastoma cells, the mutated CRXE-containing promoter shows a 60% repression of the CAT activity whereas the mutated PCE-containing promoter shows a 30% repression. In HeLa cells transfected with these promoters, co-transfection of a Crx expression vector with wild-type, but not with CRXE mutant promoter, activates CAT activity 20-fold over the background activity. Mutation of PCE alone or conversion of CRXE to PCE reduces this Crx-activated CAT activity to only 4-fold over the background activity. In the transgenic mouse experiments, none of the 12 lines with CRXE mutant promoter show significant expression of lacZ in the retina. In contrast, 9 of the 17 transgenic lines with PCE mutant promoter show photoreceptor-specific lacZ expression. Thus the Crx interaction with CRXE is essential for the photoreceptor-specific activity of the IRBP promoter in vivo. This interaction does not appear to require PCE, but is enhanced when PCE is present.

Animals↗
PubMed1999

Phthalimide analogs of CB 1954: synthesis and bioactivation.

Four novel 4-substituted 5-nitrophthalimides (5-substituted-6-nitro-1,3-dihydro-isoindol-1,3-diones), 6, 7, 10 and 11, and the known 5 are prepared as analogs of the dinitrobenzamide prodrug CB 1954, 1, and considered as potential candidates for gene-directed enzyme prodrug therapy. All the phthalimides are poor substrates for Escherichia coli nitroreductase compared to CB 1954. However, 6, 7, 10 and 11 are reduced by both the human and rat forms of DT-diaphorase; 10 is a particularly good substrate but 7 decomposes in phosphate buffer. A cell-line panel consisting of V79 cells that have been engineered to express various levels of either the human or rat forms of DT-diaphorase in an identical cellular background was used to evaluate these compounds as prodrugs activated by this enzyme. The cytotoxic effect of CB 1954 is proportional to the activity of either the rat or human enzyme but cells expressing the rat enzyme were much more sensitive (10000-fold at higher levels of DT-diaphorase activity) than cells expressing comparable levels of the human enzyme. These results demonstrate that the resistance of human tumors to CB 1954 can be accounted for solely by the kinetic properties of the enzyme for this prodrug. The nitrophthalimide analogs overcome this kinetic failing of CB 1954. However, these compounds are not activated to produce cytotoxicity in these DT-diaphorase-expressing cell lines. It is postulated their reduction products fail to undergo an acylation reaction in a manner analogous to CB 1954. Thus, reduction by DT-diaphorase is not predictive of cytotoxicity in this class of prodrugs.

Animals↗
PubMed1999

Nefazodone in post-traumatic stress disorder: results from six open-label trials.

Nefazodone, an antidepressant which blocks serotonin (5-HT)2 receptors and 5-HT reuptake, was evaluated in the treatment of post-traumatic stress disorder (PTSD) in six open-label studies involving both civilians and combat veterans. Our objective was to report this available pooled data to characterize the response of this drug in PTSD. Specifically, we looked at response rates using three different criteria, the effect of nefazodone on each PTSD cluster and individual symptoms and, lastly, variables that might predict response. One hundred and five outpatients with chronic PTSD were treated with nefazodone titrated up to 600 mg/day, 92 of whom were entered in an intent to treat analysis. We used the percentage drop in score between baseline and endpoint on main scale as a common measure to evaluate outcome. The response criterion of a drop in score of at least 30%, 40% and 50% revealed response rates of 46, 36 and 26%, respectively. Nefazodone showed a broad spectrum of action on PTSD symptoms. This profile might make nefazodone a useful drug to treat PTSD. Predictors of response include age, sex and trauma type. Double-blind, placebo-controlled clinical trials in PTSD are in progress to assess the utility of nefazodone as a treatment in this disorder.

Adult↗
PubMed1999

Tumor necrosis factor depresses myocardial contractility in endotoxemic swine.

BACKGROUND: Depression of myocardial contractility occurs in septic shock. METHODS: Fourteen pigs were instrumented to measure cardiopulmonary dynamics after a challenge of Escherichia coli endotoxin (lipopolysaccharide endotoxin, LPS). A volumetric Swan-Ganz catheter was placed via the jugular vein, and a carotid arterial line was placed into the aortic root. Eight pigs received LPS alone and six pigs received tumor necrosis factor monoclonal antibody (TNF MAb) 15 minutes before the administration of LPS. Pulmonary artery and aortic root blood were sampled for amounts of TNF. Ninety minutes after LPS administration, thoracotomy was performed to biopsy the right and left ventricles for TNF levels. Contractility was determined from the end systolic pressure-volume relationships of pressure-volume diagrams. RESULTS: Right ventricular end diastolic volume index nearly doubled and myocardial contractility decreased by 40% from baseline in the pigs receiving only LPS. Pigs that received TNF MAb had no change in myocardial contractility or right ventricular end diastolic volume index from baseline. There was a higher level of TNF in the aortic sample than in the pulmonary samples at 60 minutes. Right ventricular tissue TNF levels were significantly higher in the LPS-alone group. There was no such difference in left ventricular tissue. CONCLUSION: The left and right ventricles have different susceptibilities to TNF MAb. TNF may decrease myocardial contractility in sepsis. Blockade of TNF with TNF MAb reverses the depression of myocardial contractility and the right ventricular dilatation associated with septic shock.

Animals↗
PubMed1999

Prognostic significance of p27 expression in carcinoma of the oral cavity and oropharynx.

OBJECTIVE: To study the role of p27, a cyclin-dependent kinase inhibitor, as a prognostic indicator in squamous cell carcinoma of the oral cavity and oropharynx. STUDY DESIGN: Retrospective review of 35 patients with squamous cell carcinoma of the oral cavity and oropharynx who presented to Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois, between 1986 and 1995. METHODS: Inclusion criteria were the availability of clinical information, archival pretreatment biopsy material, and a minimum follow-up of 24 months. p27 staining was scored for frequency and intensity of tumor cell expression following immunoperoxidase staining using standard techniques. Samples of squamous epithelium from the uvula of 15 nonsmoking patients without past or present squamous cell carcinoma were used as normal controls. RESULTS: The association of p27 staining and other factors with response to treatment was evaluated by Fisher's Exact Test and with overall and disease-free survival by the Kaplan-Meier method with multivariate Cox regression. Low levels of p27 expression correlated significantly with unfavorable treatment response (P<.0001), shorter overall survival (P = .0001), and shorter disease-free survival (P = .003). Tumor site (alveolus) was also associated with shorter disease-free (though not overall) survival, but the association with p27 was independent of stage and site in multivariate analysis.

Adult↗
PubMed1999

Epidemiological characteristics of women with high grade CIN who do and do not have human papillomavirus.

OBJECTIVE: Human papillomavirus infection is an important aetiological agent associated with the development of cervical neoplasia. However, even with the most sensitive methods of detection, human papillomavirus DNA has been detected in only 90% of cases of cervical cancer and between 80%-90% of cases of dysplasia. This study aimed to determine if there are epidemiological differences between women who are positive or negative for human papillomavirus, with high grade cervical intraepithelial neoplasia (CIN). DESIGN: Four hundred and sixty women with CIN II and III lesions were studied. To ensure optimal detection of human papillomavirus DNA, two specimens (i.e. tampon and cervical biopsy) were collected from each woman and tested by three techniques: L1-polymerase chain reaction, E6-PCR and low stringency Southern blotting. A detailed questionnaire was completed and blood sample collected for determination of serum levels of beta-carotene, vitamin A and E from each patient. Human leucocyte antigen (HLA)-DQB 1 alleles were also compared between the groups of women who were positive or negative for human papillomavirus. RESULTS: Overall, human papillomavirus DNA analysis was positive in 411 women (89%). Age, number of sexual partners in the last 12 months, past pregnancy and marital status were associated with human papillomavirus detection in the crude analysis. However, in the adjusted analysis no epidemiological features remained significantly different between the human papillomavirus positive and negative patients. Moreover, examination of vitamin A, E and beta-carotene levels did not show a significant difference between the two groups of patients. However, in the HLA-DQB1 allele profile a significantly higher proportion of women who were negative for human papillomavirus had DQB1 *0201, *0603 and *0604 (P = 0.05, 0.001, 0.03, respectively). CONCLUSION: We did not find a significant difference in epidemiological factors between women with human papillomavirus positive and negative high grade CIN. However differences between the frequency of three HLA DQB1 alleles suggest that women with these allele profiles have a higher chance of clearing human papillomavirus, without affecting their chance of developing dysplasia.

Adult↗