PubMed Health⌕ Search

Biomedical subjects

Y S Lin

Publications and source records attributed to Y S Lin.

At least 73 records · Page 4Linked to original sources
PubMed1999

Requirement of I-E molecule for thymocyte apoptosis induced by staphylococcal enterotoxin B in vivo.

In vivo administration of bacterial superantigen staphylococcal enterotoxin B (SEB) to BALB/c mice led to thymus atrophy resulting from thymocyte apoptosis. In this study, we demonstrated that SEB induced a substantial reduction in thymocyte numbers in BALB/c, B10. D2 (H-2(d) haplotype), B10.BR, C3H/HeJ, C3H/HeN (H-2(k)), and (BALB/c x B6)F1 (H-2(dxb)), but caused little or no effect in I-E- strains such as B6, B10, A.BY (H-2(b)), and A.SW (H-2(s)) mice. Elimination of CD4(+)CD8(+) cells predominantly accounted for the thymocyte loss, although the numbers of other subpopulations may also be reduced. Thymocyte apoptosis was shown by an increase in the level of DNA fragmentation in BALB/c but not in B6 mice after SEB administration. Treatment with anti-I-Ed monoclonal antibody to BALB/c mice blocked SEB-induced thymocyte apoptosis when anti-I-Ad exerted less effect. In contrast to SEB, staphylococcal enterotoxin A led to comparable levels of thymus atrophy in BALB/c and B6 mice. Studies on the surface marker expression indicated that CD25 expression was upregulated on BALB/c mouse thymocytes but with only a moderate increase in B6 mice. The CD4(+)CD8(+) cells were the major (>90%) population that expressed elevated levels of CD25 in BALB/c mice. An increase in the expression of TCRalphabeta, CD3, and CD69 surface markers was also observed on thymocytes from BALB/c mice, but not from I-E- strains. The differential response of I-E+ and I-E- mice to SEB may be exploited as a model for the study of apoptosis in the thymus.

Animals↗
PubMed1999

Inhibition of hTAFII32-binding implicated in the transcriptional repression by central regions of mutant p53 proteins.

We previously identified a movable and regulable inactivation function within the central region (CRts247) of a temperature-sensitive p53 (p53(ts)) mutant, p53(N247I). Here we showed that central regions from several p53(ts) mutants behaved similarly, i.e. they repressed a neighboring activation domain only when existing in the mutant status. Using chimeric protein GAL4VP16-CRts247 as an example, we demonstrated that de novo protein synthesis was not required for the reactivation of the chimeric protein, indicating that a post-translational mechanism was involved in the control of CRts247 activity. The CRts247-conferred thermo-regulability did not work via a mechanism demanding either an alteration of the subcellular compartmentalization of or the inactivation of DNA-binding activity of the GAL4 chimera. Further, CRts247 did not function in trans, eliminating the possibility that the observed repression was because of the competition for a putative factor(s) by the mutant p53 domain. Rather, CRts247 bestowed temperature-dependent interaction with hTAFII32 to the VP16 activation domain. In a parallel experiment, CRts247 also caused a large reduction in the affinity of hTAFII32 to the p53 activation domain at the nonpermissive temperature. These results strongly suggested that inhibition of hTAFII32 binding could be one of the mechanisms responsible for the transcriptional repression by mutant p53 central regions.

Mutation↗
PubMed1999

The Asian Pacific Economic Cooperation Emerging Infections Network.

ISSUE: The Asia Pacific Economic Cooperation (APEC) has undertaken an initiative in emerging infections. PROJECT: The APEC Emerging Infections Network project uses collaborative telecommunications tools such as e-mail and a World Wide Web site to bridge the broad geographic expanse and diversity of APEC. Scientists and policymakers share information to effectively combat emerging infectious disease (EID) through surveillance, prevention, research, and control measures. RESULTS: In the project's first year, site visits compiled information on Internet access in selected economies. Information sharing via electronic lists has been successful; feedback suggests that these strategies will become increasingly useful. The Emerging Infections Network (EINet) Web site includes project information, library access, surveillance data, prevention guidelines, and distance learning resources. A pilot effort to promote the secure electronic exchange of surveillance data demonstrated that informal communications may be both preferable and more feasible during the early stages of this project. LESSONS LEARNED: Human networking is as important as technology-based networking in addressing emerging infections. Internet technology in some APEC economies is barely adequate, but is becoming more reliable and accessible. Numerous member economies are eager to be included in project activities.

Asia↗
PubMed1999

alpha-Difluoromethylornithine blocks thymocyte apoptosis via a reduction in tyrosine phosphorylation.

The effect of alpha-difluoromethylornithine on cell apoptosis was investigated. Freshly isolated mouse thymocytes were cultured in the medium alone or with dexamethasone, and apoptotic cell death was monitored after 6 h. A correlation was seen between cell apoptosis and a reduction in the polyamine levels of thymocytes. Addition of exogenous polyamines decreased the levels of apoptosis induced spontaneously in the culture medium or by dexamethasone. However, addition of alpha-difluoromethylornithine, an irreversible inhibitor of ornithine decarboxylase, to the cultures did not enhance apoptosis but rather caused inhibition of thymocyte apoptosis. Analysis of the mechanism of alpha-difluoromethylornithine-mediated inhibition of apoptosis indicated that alpha-difluoromethylornithine treatment blocked protein tyrosine phosphorylation, which was elevated drastically during the first hour of thymocyte cultivation. Treatment with the phosphotyrosine phosphatase inhibitor phenylarsine oxide reversed this inhibitory effect of alpha-difluoromethylornithine on apoptotic cell death. Our results provide an alternative mechanism for alpha-difluoromethylornithine showing the inhibition of apoptosis via reduction of protein tyrosine phosphorylation.

Animals↗
PubMed1999

Antioxidant administration inhibits exercise-induced thymocyte apoptosis in rats.

PURPOSE: The purpose of this study was to investigate the effect of antioxidant on exercise-induced apoptosis in rat thymocytes. METHODS: After exercise at 13.8 m x min(-1) for 60-90 min x d(-1) on a motor-driven drum exerciser for 2 consecutive days, rat thymocyte apoptosis was monitored by the feature of DNA fragmentation. To study the effect of antioxidant, rats were administered with butylated hydroxyanisole (BHA) for 7 d before exercise. RESULTS: Exercise could induce thymocyte DNA fragmentation as detected on electrophoretic gel and by cell death detection ELISA kit. Further studies indicated that pretreatment with antioxidant BHA to rats resulted in a blockage of exercise-induced DNA fragmentation. The concentrations of glutathione (GSH) were not significantly changed in rat thymocytes after exercise with or without BHA treatment. CONCLUSION: These results suggest that reactive oxygen species may play a role in thymocyte apoptosis induced by exercise. However, changes in GSH levels were not observed in this exercise model.

Analysis of Variance↗
PubMed1999

Streptococcal pyrogenic exotoxin B induces apoptosis and reduces phagocytic activity in U937 cells.

Treatment of U937 human monocyte-like cells with Streptococcus pyogenes led to an induction of apoptosis in these cells. A comparison between the wild-type strain and its isogenic protease-negative mutant indicated that the production of streptococcal pyrogenic exotoxin B (SPE B), a cysteine protease, caused a greater extent of apoptosis in U937 cells. Further study using purified SPE B showed that this protease alone could induce U937 cells to undergo apoptosis, which was characterized by morphologic changes, DNA fragmentation laddering on the gel, and an increase in the percentages of hypodiploid cells. The protease activity of SPE B was required for apoptosis to proceed, since treatment with cysteine protease inhibitor E64 or heat inactivation abrogated this death-inducing effect. The SPE B-induced apoptosis pathway was interleukin-1beta converting enzyme (ICE) family protease dependent. Further experiments showed that the phagocytic activity of U937 cells was reduced by SPE B. Treatment with E64 and heat inactivation both abrogated this phagocytosis-inhibitory effect. Taken together, the present data show that SPE B not only possesses the ability to induce apoptosis in monocytic cells but also helps bacteria to resist phagocytosis by host cells.

Apoptosis↗
PubMed1999

Group A Streptococcus induces apoptosis in human epithelial cells.

Internalization of group A streptococcus (GAS) by epithelial cells may have a role in causing invasive diseases. The purpose of this study was to examine the fate of GAS-infected epithelial cells. GAS has the ability to invade A-549 and HEp-2 cells. Both A-549 and HEp-2 cells were killed by infection with GAS. Epithelial cell death mediated by GAS was at least in part through apoptosis, as shown by changes in cellular morphology, DNA fragmentation laddering, and propidium iodide staining for hypodiploid cells. A total of 20% of A-549 cells and 11 to 13% of HEp-2 cells underwent apoptosis after 20 h of GAS infection, whereas only 1 to 2% of these cells exhibited spontaneous apoptosis. We further examined whether streptococcal pyrogenic exotoxin B (SPE B), a cysteine protease produced by GAS, was involved in the apoptosis of epithelial cells. The speB isogenic mutants had less ability to induce cell death than wild-type strains. When A-549 cells were cocultured with the mutant and SPE B for 2 h, the percentage of apoptotic cells did not increase although the number of intracellular bacteria increased to the level of wild-type strains. In addition, apoptosis was blocked by cytochalasin D treatment, which interfered with cytoskeleton function. The caspase inhibitors Z-VAD.FMK, Ac-YVAD.CMK, and Ac-DEVD.FMK inhibited GAS-induced apoptosis. These results demonstrate for the first time that GAS induces apoptosis of epithelial cells and internalization is required for apoptosis. The caspase pathway is involved in GAS-induced apoptosis, and the expression of SPE B in the cells enhances apoptosis.

Amino Acid Chloromethyl Ketones↗
PubMed1999

[Studies on the simultaneous measurement of several cephalosporins by RP-HPLC (I)].

This paper reported the research on the simultaneous separation and determination of six cephalosporins by RP-HPLC. Six cephalosporins are cefalcor, cefalexin, cefradine, cefadroxil, cefominox and cefoxitin. The analytical conditions for this method were as follows: a Hypersil ODS C18(200 mm x 4.6 mm i.d., 5 microns), detection wavelength: 254 nm; a mobile phase solution of 50 mmol/L monopotassium phosphate (pH 3.4)-acetonitrile (87.5:12.5) and DAD detector. The flow rate was 1.0 mL/min. The calibration curves of the six compounds were linear, the correlation coefficients were 0.9951 for cefominox, 0.9999 for the others, the range were 164 ng-16.4 micrograms for cefominox, 99 ng-9.934 micrograms for cefadroxil, 104 ng-10.358 micrograms for cefalcor, 122 ng-12.224 micrograms for cefalexin, 107 ng-10.702 micrograms for cefradine and 115 ng-11.506 micrograms for cefoxitin. The recovery rates were 103.5% for cefominox, 99.3% for cefadroxil, 101.4% for cefalcor, 101.5% for cefalexin, 98.7% for cefradine and 97.6% for cefoxitin. Six cephalosporins were all stable in 50 mmol/L monopotassium phosphate (pH 3.4-4.6). When preparations of these cephalosporins were determined, it is indicated there were no difference between the results by using this method and the pharmacopoeia methods. The total separation time of these cephalosporins was within fifteen minutes. This method is simple, sensitive, rapid and accurate.

Anti-Bacterial Agents↗
PubMed1999

Preclinical pharmacokinetics, interspecies scaling, and tissue distribution of a humanized monoclonal antibody against vascular endothelial growth factor.

Vascular endothelial growth factor (VEGF) plays a crucial role in angiogenesis and in pathological processes such as tumor growth, rheumatoid arthritis, and ocular neovascularization. A recombinant humanized monoclonal antibody (rhuMAb), rhuMAb VEGF, has been developed to inhibit the effects of VEGF in the treatment of solid tumors. Intravenous and s.c. pharmacokinetic studies were conducted in mice, rats, and cynomolgus monkeys. In addition, the tissue distribution of i.v. 125I-rhuMAb VEGF was investigated in rabbits. At a dose of approximately 10 mg/kg, the clearance of rhuMAb VEGF from the serum was 15.7 ml/day/kg in mice, 4.83 ml/day/kg in rats, and 5.59 ml/day/kg in cynomolgus monkeys, and the terminal half-life ranged from 6 to 12 days in all species. After s.c. administration, rhuMAb VEGF had a bioavailability of 69% in rats and 100% in mice and cynomolgus monkeys. Pharmacokinetic data in mice, rats, and cynomolgus monkeys were used to predict the pharmacokinetics of rhuMAb VEGF using allometric scaling in humans. The predicted serum clearance of rhuMAb VEGF in humans was 2.4 ml/day/kg and the terminal half-life was 12 days. Two hours after i.v. bolus administration of 125I-rhuMAb VEGF in rabbits, trichloroacetic acid-precipitable radioactivity was noted primarily in the plasma, with lesser amounts in highly perfused tissues such as kidneys, testes, spleen, heart, and lungs. At 48 h after dosing, trichloroacetic acid-precipitable radioactivity was noted in plasma with minimal distribution to testes, bladder, heart, lungs, and kidneys. Tissue distribution and pharmacokinetic data indicate that rhuMAb VEGF is cleared slowly and distributes to specific sites in the body.

Animals↗
PubMed1998

Molecular cloning of bovine telomerase RNA.

Telomerase is a ribonucleoprotein reverse transcriptase essential for the maintenance of telomere length. However, the available information concerning the biochemical and structural aspects of mammalian telomerases is scarce, primarily due to the low abundance of these enzymes and the difficulty and expense involved in its purification. To overcome these problems, we started to purify and characterize telomerase from bovine testis. Bovine telomerase was purified over columns of hydroxyapatite, DEAE-Sepharose, heparin-agarose, phenyl-agarose and spermine-agarose. In a sedimentation study performed using a 15-40% glycerol gradient, partially purified bovine telomerase exhibited an apparent molecular weight of more than 1000 kDa. One 435-bp RNA, bTR, was cloned from the most purified telomerase fraction and shown to be co-purified with telomerase activity in a glycerol gradient. bTR shares 83% similarity to the human telomerase RNA and 65% to the mouse telomerase RNA. A putative template region encompassing 10 nucleotides (5'-CUAACCCUAA-3') complementary to the mammalian telomere sequence (TTAGGG)n is located between nucleotides 38-47 of bTR. Besides, the bTR 5'-flanking region shares only three regulatory elements with that of hTR: a TATA-like sequence, a CCAAT box and an E1A-F box. Furthermore, the addition of in-vitro transcribed bTR reconstituted telomerase activity after removal of the endogenous bTR by micrococcal nuclease digestion. Northern blot analysis identified a single RNA of about 430-440 nucleotides expressed in the bovine testis and an immortalized bovine cell line. Taken together, these data strongly suggest that bTR is the RNA component of bovine telomerase.

Animals↗
PubMed1998

The N-terminal 178-amino-acid domain only of the SV40 large T antigen acts as a transforming suppressor of the HER-2/neu oncogene.

The deregulation of the HER-2/neu protooncogene was demonstrated in a wide variety of human cancers and shown to be correlated with the progress of malignancy and metastasis in animal models. Repression of HER-2/neu overexpression suppressed the malignant phenotypes of HER-2/neu-overexpressing cancer cells. This suggested that HER-2/neu may be a good target for developing anti-cancer drugs. We found a deletion mutant of simian virus 40 (SV40) large T antigen (LT) suppresses the HER-2/neu oncogene expression at the transcriptional level. PCR clones of this mutant SV40LT, named LT425, which contains the N-terminal region of amino acid residues 1-178 of SV40LT, were subcloned and stably transfected into the HER-2/neu-overexpressing human ovarian cancer SKOV3.ip1 cells. These LT425 clones were found to be able to down-regulate the endogenous production of p185(HER-2/neu). In addition, the LT425-expressing stable transfectants showed reduced growth rate, low soft agarose colony forming ability, and low tumorigenic potential as compared with the parental line. These data suggested that the N-terminal 178 amino acids domain only of SV40LT may act as a transforming repressor of HER-2/neu oncogene.

Amino Acid Sequence↗
PubMed1998

Inhibition of immune cell proliferation with haloperidol and relationship of tyrosine hydroxylase expression to immune cell growth.

Previous studies indicated that exogenous dopamine and its agonists directly regulated mitogen-induced immune cell proliferation. In this study, we further investigated role of endogenous dopamine in immune cell growth. Haloperidol, a general antagonist for dopamine receptors, could reduce the cell growth rate of T cell hybridoma (10I) and rat nervous pheochromocytoma cells (PC12). Tyrosine hydroxylase (TH) catalyzes the initial rate-limiting step of catecholamine biosynthesis in the nervous system. Flow cytometric analysis indicated the expression of TH in various immune cells. The presence of TH in PC12 cells was used as a control. Temporal studies indicated that the expression of TH increased during 10I cell growth. Both alpha-methyl-p-tyrosine and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine reduced TH expression and cell growth in a dose-dependent manner. These results suggest that immune T cells express TH which is correlated to cell growth, and that dopamine released from these cells may bind to the receptors to act in an autocrine or paracrine way.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1998

ED staff members' personal use of complementary therapies and their recommendations to ED patients: a southeastern US regional survey.

BACKGROUND: Use of complementary and alternative therapies has increased in the United States during the past 5 years. Little is known about the use of these therapies in emergency departments. METHODS: The Center for the Study of Complementary and Alternative Therapies, University of Virginia, surveyed staff in 10 emergency departments in the southeast region of the United States with the purpose of exploring ED practitioners' personal use of complementary therapies and recommendations of these therapies to patients. RESULTS: ED staff reported back rub or massage, music, and prayer or spiritual practices as the 3 most frequently used complementary therapies for personal well-being. Back rub or massage and spiritual practices including prayer and group support were most frequently recommended to patients. Clinicians expressed interest in acquiring additional knowledge of complementary therapies and support for integration of these therapies in emergency departments. CONCLUSIONS: Use of complementary therapies for personal well-being and for patient care by ED staff in the southeast region of the United States is limited. Most ED staff are not familiar with these therapies, but a majority of staff (70%) want to learn more about them. Findings suggest that ED nurses would like additional training in, and better referral patterns to, complementary therapies.

Adult↗
PubMed1998

The telomeres of Streptomyces chromosomes contain conserved palindromic sequences with potential to form complex secondary structures.

The chromosomes of the gram-positive soil bacteria Streptomyces are linear DNA molecules, usually of about 8Mb, containing a centrally located origin of replication and covalently bound terminal proteins (which are presumably involved in the completion of replication of the telomeres). The ends of the chromosomes contain inverted repeats of variable lengths. The terminal segments of five Streptomyces chromosomes and plasmids were cloned and sequenced. The sequences showed a high degree of conservation in the first 166-168bp. Beyond the terminal homology, the sequences diverged and did not generally cross-hybridize. The homologous regions contained seven palindromes with a few nucleotide differences. Many of these differences occur in complementary pairs, such that the palindromicity is preserved. Energy-optimized modelling predicted that the 3' strand of the terminal palindromes can form extensive hairpin structures that are similar to the 3' ends of autonomous parvovirus genomes. Most of the putative hairpins have a GCGCAGC sequence at the loop, with the potential to form a stable single C-residue loop closed by a sheared G:A pairing. The similarity between the terminal structures of the Streptomyces replicons and the autonomous parvoviral genomes suggests that they may share some structural and/or replication features.

Base Sequence↗
PubMed1998

Peripheral neural modulation of endotoxin-induced hyperventilation.

OBJECTIVE: To delineate the role of the peripheral neural reflexes involved in modulating hyperventilation during endotoxemia. DESIGN: A prospective, randomized, controlled, multigroup study. SETTING: Research animal laboratory. SUBJECTS: Adult Sprague-Dawley rats (n=43; 354+/-24 g) of either gender. INTERVENTIONS: Eight rats received a sham operation on their vagus, carotid sinus, and aortic nerves before the administration of a saline vehicle to serve as the time control. In the endotoxin group, 11 rats received a sham operation before endotoxin challenge. The remaining 24 rats received bilateral vagotomy (n=8), perivagal capsaicin treatment (n=8), or denervation of peripheral chemoreceptors (n=8) before endotoxin challenge. After the breathing pattern returned to a steady state, endotoxin (L-4130, serotype 0111, B4 lipopolysaccharide; 50 mg/kg) was injected into the vein. The rat's respiration was then monitored continuously for 5 hrs or until the animal died. MEASUREMENTS AND MAIN RESULTS: The respiratory rate and tidal volume did not change over the 5-hr observation period in the time control group. In the endotoxin group, the respiratory rate increased significantly from baseline (135.4%) 2 hrs after endotoxin challenge and increased persistently until the rats died. The tidal volume increased gradually to < or =132.8% of baseline 4 hrs after endotoxin challenge. Bilateral cervical vagotomy and perineural capsaicin treatment of the vagus nerves eliminated the tachypnea response to endotoxin injection. Denervation of the peripheral chemoreceptor accentuated the hyperventilation response to endotoxin, and resulted in the shortest survival time. CONCLUSIONS: Both lung vagal C-fiber afferents and peripheral chemoreceptors are involved in modulating the hyperventilation response after endotoxin challenge in rat models. Stimulation of vagal C-fiber afferents increased the respiratory rate. Conversely, the role of peripheral chemoreceptors was to restrain the hyperventilatory response and these receptors may play a protective role during endotoxemia.

Animals↗
PubMed1998

Pharmacokinetics and pharmacodynamics of sibrafiban (Ro 48-3657), an orally active IIb/IIIa antagonist, administered alone or in combination with heparin, aspirin, and recombinant tissue-type plasminogen activator in beagles.

This study characterized the pharmacokinetics (PK) and pharmacodynamics (PD) of sibrafiban (Ro 48-3657) in the presence of aspirin, heparin, and recombinant tissue-type plasminogen activator (rt-PA) in beagles. Sibrafiban is a double prodrug that undergoes bioconversion to the inactive prodrug Ro 48-3656 and to the active IIb/IIIa antagonist, Ro 44-3888, after oral administration. After oral sibrafiban, peak Ro 48-3656 plasma concentrations were observed earlier than Ro 44-3888 and were five- to sixfold higher than Ro 44-3888 peak concentrations. Administration of sibrafiban with heparin and aspirin or heparin and rt-PA did not alter sibrafiban PK. Ro 48-3656 and Ro 44-3888 PK and inhibition of platelet-aggregation profiles in groups treated with sibrafiban and heparin/aspirin or sibrafiban and heparin/rt-PA were similar to those of the group receiving sibrafiban alone. Sibrafiban resulted in >80% inhibition of adenosine diphosphate (ADP)-mediated platelet aggregation and an approximate sixfold increase in bleeding time (BT) compared with baseline measurements. The BT increase was greater in the sibrafiban, heparin, and rt-PA-treated group, during rt-PA administration, compared with the group treated with sibrafiban alone. The recovery of platelet aggregation may be slower after administration of sibrafiban with heparin and rt-PA. Sibrafiban had no effect on rt-PA PK or heparin PD.

Administration, Oral↗
PubMed1998

Induction of thymocyte apoptosis in mice by Yersinia enterocolitica products.

In-vivo administration of the culture supernates from Yersinia enterocolitica resulted in thymus atrophy in C3H/HeJ mice, known to be lipopolysaccharide (LPS)-nonresponders. The thymocytes underwent apoptosis as characterised by fragmented DNA ladders on agarose gel electrophoresis, a cell death detection ELISA and a morphological study by the TUNEL reaction. As a control, LPS treatment did not induce thymocyte apoptosis in C3H/HeJ mice. Flow cytometric analysis indicated that thymus atrophy was due predominantly to the deletion of CD4+ CD8+ T cells. When cells were undergoing apoptosis, an elevation in the percentage of T-cell receptor (TCR)-alphabeta(high) cells was observed at 24 h, which was correlated with the increase in the percentages of cells expressing high levels of the Vbeta6 and Vbeta8 TCR. Gel electrophoretic analysis demonstrated the presence of protein bands with mol.wts ranging from 17 to 65 kDa in Y. enterocolitica culture supernates.

Animals↗