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Biomedical subjects

S Lin

Publications and source records attributed to S Lin.

At least 181 records · Page 10Linked to original sources
PubMed1999

No association between the intronic presenilin 1 polymorphism and Alzheimer's disease in the Chinese population.

Wragg et al. [1996: Lancet 347:509-512] recorded an association between the intron-based presenilin 1 (PS1) genotype 1/1 and late-onset Alzheimer's disease (AD). This study was performed to determine if there is a similar association in the Chinese population. Ninety-one AD cases, 50 multiinfarct dementia (MID) patients, and 73 age-matched normal controls were recruited. Genotyping of PS1 and apolipoprotein E (APOE) was performed by the methods of polymerase chain reaction and restriction fragment length polymorphism. In AD, MID, and normal controls PS1 allele 1 frequency was 0.6703, 0.5600, and 0.6301, respectively; PS1 allele 2 frequency was 0.3297, 0.4400, and 0.3699, respectively. No association was detected between these diseases and any PS1 allele or genotype. There was only a nearly significant negative association between MID and PS1 genotype 1/1 in the subgroup population bearing APOE allele E4 (odds ratio = 0.2753, P = 0.0776). Our results do not support the conclusion that the intronic PS1 polymorphism is associated with Alzheimer's disease.

Aged↗
PubMed1999

Positive and negative cis-acting elements are required for hematopoietic expression of zebrafish GATA-1.

GATA-1 is a transcription factor required for development of erythroid cells. The expression of GATA-1 is tightly restricted to the hematopoietic lineage. Using transgene constructs containing zebrafish GATA-1 genomic sequences and the green fluorescent protein (GFP) reporter gene, we previously showed that a 5.6-kb enhancer/promoter fragment is sufficient to direct erythroid-specific expression of the GFP. In this study, we used enhancer/promoter fragments containing various deletion and point mutations to further characterize the cis-acting elements controlling tissue-specific GATA-1 expression. We report here the identification of distinct cis-acting elements that cooperate to confer on GATA-1 its hematopoietic expression pattern. A CACCC box, located 142 bp upstream of the translation start codon, is critical for the initiation of GATA-1 expression. A distal double GATA element is required for maintaining and enhancing the hematopoietic expression of GATA-1. The erythroid-specific activity of the GATA-1 promoter is also enhanced by a 49-bp sequence element located 218 bp upstream of the CACCC element and a CCAAT box adjacent to the double GATA motif. Finally, the hematopoietic specificity of the GATA-1 promoter is secured by a negative cis-acting element that inhibits expression in the notochord.

Animals↗
PubMed1999

Using affinity capillary electrophoresis to evaluate average binding constant of 18-mer diphosphotyrosine peptide to antiphosphotyrosine Fab.

We used affinity electrophoresis in capillaries to investigate the interaction between a monovalent antiphosphotyrosine antibody fragment, antigen-binding fragment (Fab), and a divalent antigen (dAg), an 18-mer diphosphopeptide phosphorylated on two-site tyrosine residues. The migration shift behavior of Fab in electrophoretic solution was observed and the quantitative expression was presented to estimate the arithmetical average value of the intrinsic affinities for two epitopes on the dAg with the Ag binding site on the Fab. In dAg excess, based on measurement of mobility changes of Fab analytes at different dAg concentrations, the experimental average dissociation constant (Kd = 27.7 microM) was calculated. It was also found that the structural variation of the two epitopes for binding specificity to the Ag-binding domain of Fab is not apparent. Moreover, the Kd values of Fab-dAg complexes were measured at higher electric fields and shown to be independent of changes in the electric field. Thus, under conditions where the total dAg concentration is in excess of the total Fab concentration, the method and quantitative expression which we developed is generally useful for the understanding of molecular interaction for an unlabeled monovalent receptor and its divalent ligand in free solution.

Amino Acid Sequence↗
PubMed1999

A multiple locus analysis of the collaborative study on the genetics of alcoholism data set.

Parametric and nonparametric statistical methods have been applied to the alcohol dependence data set collected in the Collaborative Study on the Genetics of Alcoholism (COGA). Our nonparametric linkage analyses (NPL) were based on the S(all) statistic of GENEHUNTER [Kruglyak et al., 1996] and the improved NPL statistic of GENEHUNTER-PLUS [Kong and Cox, 1997]. Based on likely regions for alcohol susceptibility genes identified from our nonparametric analyses, we reanalyzed the data using several two-locus models. We used the TMLINK program [Lathrop and Ott, 1990] in the LINKAGE package for these parametric analyses.

Alcoholism↗
PubMed1999

Initial experience of using an active beam delivery technique at PSI.

At PSI a new proton therapy facility has been assembled and commissioned. The major features of the facility are the spot scanning technique and the very compact gantry. The operation of the facility was started in 1997 and the feasibility of the spot scanning technique has been demonstrated in practice with patient treatments. In this report we discuss the usual initial difficulties encountered in the commissioning of a new technology, the very positive preliminary experience with the system and the optimistic expectations for the future. The long range goal of this project is to parallel the recent developments regarding inverse planning for photons with a similar advanced technology optimized for a proton beam.

Humans↗
PubMed1999

Functional muscarinic m3 receptor expressed in gastric cancer cells stimulates tyrosine phosphorylation and MAP kinase.

Human gastric cancer cells were used to examine the trophic effect of the muscarinic m3 receptor subtype. Expression of the m3 receptor was detected in five of eight cell lines examined, MKN-1, 7, 28, 74, and TMK-1 cells. An increase in intracellular Ca2+ in response to carbachol was observed in more than 90% of TMK-1 cells, allowing us to use these cells in the following experiments. Western blot analysis showed that carbachol predominantly phosphorylated tyrosine in a 100-kDa protein. While mitogen-activated protein (MAP) kinase activity in the presence of 100 microM carbachol or 10 ng/ml transforming growth factor (TGF)alpha was augmented to 15- to 60-fold of the baseline level for 5min, the activation was transient. Pretreatment of the cells with 1 microM phorbol 12-myristate 13-acetate abolished carbacol-induced MAP kinase activation, whereas no suppression was observed in the presence of 500 nM Calphostin C (Kyowa Medex, Tokyo Japan), a specific protein kinase C inhibitor. No DNA synthesis or cell proliferation was observed in the presence of carbachol. These results indicate that stimulation of the m3 subtype leads to tyrosine phosphorylation and MAP kinase activation, but is unlikely to have trophic effects in gastric mucosal cells.

Atropine↗
PubMed1999

Femtosecond spectroscopic observations of initial intermediates in the photocycle of the photoactive yellow protein from Ectothiorhodospira halophila.

Femtosecond time-resolved absorbance measurements were used to probe the subpicosecond primary events of the photoactive yellow protein (PYP), a 14-kD soluble photoreceptor from Ectothiorhodospira halophila. Previous picosecond absorption studies from our laboratory have revealed the presence of two new early photochemical intermediates in the PYP photocycle, I(0), which appears in </=3 ps, and I(0)(double dagger), which is formed in 220 ps, as well as stimulated emission from the PYP excited state. In the present study, kinetic measurements at two excitation wavelengths (395 nm and 460 nm) on either side of the PYP absorption maximum (446 nm) were undertaken using 100-fs pump and probe pulses. Global analysis over a range of probe wavelengths yielded time constants of 1.9 ps for the photochemical formation of the I(0) intermediate via the PYP excited state, and 3.4 ps for the repopulation of the ground state from the excited state. In addition to these pathways, 395 nm excitation also initiated an alternative route for PYP excitation and photochemistry, presumably involving a different excited electronic state of the chromophore. No photochemical intermediates formed before I(0) were observed. Based on these data, a quantum yield of 0.5-0.6 for I(0) formation was determined. The structural and mechanistic aspects of these results are discussed.

Bacteria↗
PubMed1999

Topographical characteristics and shear bond strength of tooth surfaces cut with a laser-powered hydrokinetic system.

STATEMENT OF PROBLEM: Erbium lasers, specifically Er;YAG and Er, Cr;YSGG that emit in the near red wavelengths, cut both enamel and dentine. Bonding to these cut surfaces with composites has not been assessed for all laser systems. PURPOSE: This investigation assessed the shear bond strength of composite bonded to tooth structure treated with an Er,Cr;YSGG-powered hydrokinetic system (HKS, Millennium system) and then was compared with surfaces treated with a carbide bur. MATERIAL AND METHODS: Extracted human molars were cut into enamel and dentin with both systems. Nonetched and acid-etched subgroups were evaluated. Shear bond strength was measured with an Instron test machine with a knife-edge loading head. In addition, SEMs were evaluated. RESULTS: There were no significant differences in shear bond strength between etched bur cut (23.3 +/- 2.5 MPa), etched laser-cut enamel (23.7 +/- 4.5 MPa), and nonetched laser-cut enamel (20.5 +/- 2.8 MPa). For nonetched enamel, bond strength values for laser-cut surfaces were significantly higher than the bur-cut surfaces (8.7 +/- 4.3 MPa). Bond strength differences for dentin between bur (14.3 +/- 1.7 MPa) and laser cuts (11.5 +/- 4.3 MPa) were not significant (P =.03). SEM revealed that laser cutting of enamel did not cause formation of a smear layer. CONCLUSION: There were no significant differences in shear bond strength between etched bur-cut, etched laser-cut, and nonetched laser-cut enamel. With nonetched enamel, bond strength values for nonetched laser-cut surfaces were significantly higher than for the bur-cut surfaces. No bond strength differences between bur and laser cutting existed for dentin. Similar topography was observed for bur and laser prepared surfaces of etched enamel and nonetched dentin.

Acid Etching, Dental↗
PubMed1999

Chromatography and electrophoresis on chips: critical elements of future integrated, microfluidic analytical systems for life science.

Liquid chromatography and electrophoresis played a major role in the life-science revolution, most strikingly in protein purification, peptide fractionation and sequencing, amino acid analysis, and DNA sequencing. The objective of this article is to examine the potential role of separation systems in the continuing evolution of biochemistry, biotechnology and molecular biology. Very small chip-based systems may change how chemical analyses in biology, medical research and health care evolve over the next decade.

Biological Science Disciplines↗
PubMed1999

Altered hypothalamic c-Fos-like immunoreactivity in diet-induced obese mice.

High-fat diet can induce obesity. However, it is not known if the neural activity of the hypothalamus is altered under high-fat diet. The aim of the present study is to search for the altered hypothalamic neuronal activity in C57BI/6J mice fed a high-fat diet for 15 weeks. Hypothalamic c-Fos-like immunoreactivity (FLI) and serum leptin were measured after mice were fed a high-fat diet for 15 weeks. Our results demonstrate that increased body weight and serum leptin are accompanied by an elevated neuronal c-Fos-like immunoreactivity in the lateral hypothalamus, the lateral part of the dorsomedial hypothalamic and perifornical nuclei of diet-induced obese mice. Fasting increases FLI neurons in the arcuate hypothalamic nucleus and decreases FLI neurons in the lateral hypothalamic area and dorsomedial hypothalamic nucleus of both diet-induced obese and lean mice. The current data suggest that constantly activated status of these neurons in the hypothalamus may be responsible for differences in body weight and serum leptin between obese and lean mice.

Animals↗
PubMed1999

Alpha-galactose based neoglycopeptides. Inhibition of verotoxin binding to globotriosylceramide.

Solution and solid phase strategies for the synthesis of alpha-galactose based neoglycopeptide derivatives 2-13 were developed. Neoglycopeptides generated were tested for the inhibition of verotoxin binding to globotriosylceramide (Gb3) using ELISA. Among all of the compounds tested, only the lipid derivatives of neoglycopeptides, 11, 12 and 13 were found to be inhibitors, IC50 = 2.0 mM (11b and 12c) and 0.2 mM (11c and 13c). All of the inhibitors (11b, 11c, 12c and 13c) have a similar branching of the two alpha-galactosyl units at the N-terminal glycine residue of a short peptide and a lipid moiety attached at the C-terminal site. Both of these factors seem to be crucial for the inhibition. It is interesting to note that the inhibitors have only a portion of the natural trisaccharide ligand. The secondary groups either may contribute in sub-site oriented interactions with the protein receptors or may mimic the internal sugar units of the cell-surface ligand, Gb3.

Anti-Infective Agents↗
PubMed1999

Lipid, polyamide, and flavonol phagostimulants for adult western corn rootworm from sunflower (Helianthus annuus L.) pollen.

Adult Diabroticites including western corn rootworm (WCR), Diabrotica virgifera virgifera LeConte, consume pollen of corn, squash, sunflower, and other species. Short-chain neutral amino acids in methanol-water extracts of pollen have been previously identified in our laboratory as strong phagostimulants for Diabrotica. Bioassay-driven fractionation was used to characterize the interacting lipid and midpolarity phagostimulants for adult WCR in Giant Gray Stripe sunflower, Helianthus annuus L., pollen. Lipids rich in omega3-linolenic acid including triglycerides, free fatty acids, phosphatidylethanolamines, phosphatidic acids, and phosphatidylcholines were highly phagostimulatory. Other important phagostimulatory components included a hydroxycinnamic acid-polyamine amide, N(1),N(5),N(10)-tri[(E)-p-coumaroyl]spermidine, and a flavonol, quercetin beta-3-O-glucoside. The structural characteristics of these phagoactive compounds and their role in the pollinivory specialization of rootworm beetles are discussed.

Animals↗
PubMed1999

Methylarsenicals and arsinothiols are potent inhibitors of mouse liver thioredoxin reductase.

Thioredoxin reductase (TR, EC 1.6.4.5) was purified 5800-fold from the livers of adult male B6C3F1 mice. The estimated molecular mass of the purified protein was about 57 kDa. The activity of the purified enzyme was monitored by the NADPH-dependent reduction of 5, 5'-dithiobis(2-nitrobenzoic acid) (DTNB); this activity was fully inhibited by 1 microM aurothioglucose. Arsenicals and arsinothiols, complexes of As(III)-containing compounds with L-cysteine or glutathione, were tested as inhibitors of the DTNB reductase activity of the purified enzyme. Pentavalent arsenicals were much less potent inhibitors than trivalent arsenicals. Among all the arsenicals, CH(3)As(III) was the most potent inhibitor of TR. CH(3)As(III) was found to be a competitive inhibitor of the reduction of DTNB (K(i) approximately 100 nM) and a noncompetitive inhibitor of the oxidation of NADPH. The inhibition of TR by CH(3)As(III) was time-dependent and could not be reversed by the addition of a dithiol-containing molecule, 2,3-dimercaptosuccinic acid, to the reaction mixture. The inhibition of TR by CH(3)As(III) required the simultaneous presence of NADPH in the reaction mixture. However, unlike other pyridine nucleotide disulfide oxidoreductases, there was no evidence that mouse liver TR was inactivated by exposure to NADPH. Treatment with CH(3)As(III) did not increase the NADPH oxidase activity of the purified enzyme. Thus, CH(3)As(III), a putative intermediate in the pathway for the biomethylation of As, is a potent and irreversible inhibitor of an enzyme involved in the response of the cell to oxidative stress.

Animals↗
PubMed1999

Up-regulation of H2 receptor and adenylate cyclase in rabbit parietal cells during prolonged treatment with H2-receptor antagonists.

Intragastric hyperacidity occurs after abrupt withdrawal of histamine H2-receptor antagonists, and the prolonged administration of these agents induces tachyphylaxis of the inhibitory effects on gastric acid secretion. We examined the effect of the prolonged administration of H2-receptor antagonists on the H2-receptor signaling system in parietal cells isolated from rabbits that had received H2-receptor antagonists for 14 days. [125I]aminopotentidine (APT) binding sites to H2 receptors in parietal cell membranes were increased without any significant change in the affinity for [125I]APT. The expression of Gs(alpha), guanosine triphosphate (GTP)-binding protein coupled to H2 receptor, was slightly increased. Basal as well as GTP- or histamine-stimulated cAMP production was increased, but no significant change was observed in the presence of an H2-receptor antagonist. The up-regulation of the H2 receptor and adenylate cyclase appeared to cause hypersecretion of acid after withdrawal of H2-receptor blockade.

Adenylyl Cyclases↗
PubMed1999

Relative efficiencies of the chi-square recombination models for gene mapping with human pedigree data.

In the paper by Goldstein et al. (Genomics, 1995), the authors carried out a simulation study to investigate the relative efficiencies of a no interference linkage analysis to an analysis with certain models that allow for interference. They showed that, for completely informative and independent recombination data, the analysis with the no interference model was inefficient, in the present of interference. In practice, the assumption of completely informative markers is unrealistic with data from human pedigrees. We report the results of a study investigating whether this conclusion still holds for gametes arising within pedigrees. We consider the same two mapping problems as Goldstein et al.: exclusion mapping and gene ordering. The results obtained were consistent with their findings, although the efficiency gains for analyses using the chi-square model were not as great in some cases. This is not unexpected with less than fully informative data. These results point to the need for research of developing new statistical and computational methods to incorporate interference into multipoint linkage mapping using pedigree data. This would make efficient use of available, but sometimes scarce data, especially in disease gene mapping.

Alleles↗
PubMed1999

Transdermal testosterone delivery: comparison between scrotal and nonscrotal delivery systems.

The purpose of this investigation was to study the bioequivalence of two testosterone transdermal delivery systems (T-TDSs). Testoderm, designed to deliver testosterone through scrotal skin, and Androderm, designed for nonscrotal permeation. In vitro permeation and release kinetics as well as in vivo pharmacokinetics in the castrated Yucatan miniature swine (minipigs) model of both T-TDSs were studied side by side under the same experimental conditions. In vitro skin permeation kinetics studies demonstrated that testosterone permeates through minipig dorsal skin at zero-order kinetics from both T-TDSs. The nonscrotal T-TDS, however, has a permeation rate which is approximately 13 times higher than that for the scrotal T-TDS. The release of testosterone from the nonscrotal T-TDS showed a biphasic release profile between cumulative amount released and time, whereas a monophasic release profile between cumulative amount released and square root of time was observed for the scrotal T-TDS. Pharmacokinetic analysis of plasma testosterone profiles in minipigs indicated a significant difference (p < 0.001) in daily dose of testosterone delivered (1.20 versus 4.83 mg/day), maximum concentration (Cmax) (54.2 versus 218.0 ng/dl), and area under concentration-time curve (AUC0-28)[665 versus 3208 (ng/dl) x hr] between these T-TDSs. However, there is no difference in time to reach Cmax mean residence time, and daily-delivered-dose-normalized Cmax and AUC0-28. The difference in pharmacokinetic profiles resulted from the difference in daily doses delivered, which could be attributed remarkably to the difference in permeation rate (approximately 13-fold) between the nonscrotal and scrotal T-TDSs.

Administration, Cutaneous↗
PubMed1999

Flower Structure and Reproductive Biology in Aspidosperma quebracho-blanco (Apocynaceae), a Tree Pollinated by Deceit.

Flower structure, attractants, breeding system, and visitors were studied in Aspidosperma quebracho-blanco, a South American mass-flowering tree with simple moth-pollinated flowers and without floral reward. Flowers are protandrous, having an initial male phase for 2 d. The pendulous and horizontal flower position and protandry prevent self-pollination. Although an inconspicuous annular floral nectary is located at the ovary base, nectar is not secreted. Nonstructural, extrafloral nectaries have been found on the external surface of the calyx and corolla, the first report of the kind for the family. Ants, wasps, flies, and beetles collect the extrafloral exudate composed of fructose, glucose, and sucrose. Experiments indicate that natural selfing (autogamy) and agamospermy are unlikely to occur (0% success), but artificial selfing indicates self-compatibility (70% success). A very low natural fruit to flower ratio (0.03) was obtained. Floral features and nocturnal opening indicate that these flowers would be pollinated by moths that nocturnally visit the species (Noctuidae, Pyraloidea) finding no floral reward. We suggest a nonmodel deception mechanism: providing the same cues as most moth flowers, this tree seems to be dependent upon sympatric rewarding plants that share the same pollinators.

Journal Article↗