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Biomedical subjects

L Yang

Publications and source records attributed to L Yang.

At least 415 records · Page 23Linked to original sources
PubMed1998

Negative regulation of Wee1 expression and Cdc2 phosphorylation during p53-mediated growth arrest and apoptosis.

The G2 cell cycle checkpoint protects cells from potentially lethal mitotic entry after DNA damage. This checkpoint involves inhibitory phosphorylation of Cdc2 at the tyrosine-15 (Y15) position, mediated in part by the Wee1 protein kinase. Recent evidence suggests that p53 may accelerate mitotic entry after DNA damage and that the override of the G2 checkpoint may play a role in the induction of apoptosis by p53. To determine the biochemical mechanism by which p53 inactivates the G2 checkpoint, the effects of p53 activation on Wee1 expression, Cdc2-Y15 phosphorylation, and cyclin B1-associated Cdc2 kinase activity were examined. Under conditions of either growth arrest or apoptosis, p53 activation resulted in the down-regulation of Wee1 expression and dephosphorylation of Cdc2. A parallel increase in cyclin B1/Cdc2 kinase activity was observed during p53-mediated apoptosis. Negative regulation of the Wee1 expression and Cdc2 phosphorylation by p53 was also evident in thymus tissue from p53+/+ mice but not from p53-/- mice. Inactivation of the G2 checkpoint may contribute to the tumor suppressor activity of p53.

Animals↗
PubMed1998

Coenzyme Q10 administration increases brain mitochondrial concentrations and exerts neuroprotective effects.

Coenzyme Q10 is an essential cofactor of the electron transport chain as well as a potent free radical scavenger in lipid and mitochondrial membranes. Feeding with coenzyme Q10 increased cerebral cortex concentrations in 12- and 24-month-old rats. In 12-month-old rats administration of coenzyme Q10 resulted in significant increases in cerebral cortex mitochondrial concentrations of coenzyme Q10. Oral administration of coenzyme Q10 markedly attenuated striatal lesions produced by systemic administration of 3-nitropropionic acid and significantly increased life span in a transgenic mouse model of familial amyotrophic lateral sclerosis. These results show that oral administration of coenzyme Q10 increases both brain and brain mitochondrial concentrations. They provide further evidence that coenzyme Q10 can exert neuroprotective effects that might be useful in the treatment of neurodegenerative diseases.

Administration, Oral↗
PubMed1998

Identification of hydrazine in commercial preparations of carnosine and its influence on carnosine's antioxidative properties.

Commercial preparations of synthetic carnosine are commonly used by researchers to investigate carnosine's biological functions and potential applications. Our studies on the interaction of synthetic carnosine and aldehydic lipid oxidation products have led to the detection and structural identification of hydrazine, a strong reducing agent. The concentrations of hydrazine in various sources of commercial carnosine were in the range of 0.01-0.20% (w/w). The levels of contaminating hydrazine in commercial carnosine were capable of interfering with the analyses of headspace aldehydes, malonaldehyde, and thiobarbituric acid-reactive substances. Since hydrazine can potentially interfere with lipid oxidation reactions and measurement of lipid oxidation products, it will be necessary to use purified carnosine to reevaluate carnosine's biological and chemical properties.

Aldehydes↗
PubMed1998

A reduction-pyrolysis-catalysis synthesis of diamond

Diamond powder was synthesized through a metallic reduction-pyrolysis-catalysis route with the reaction of carbon tetrachloride and sodium at 700 degreesC, in which the sodium was used as reductant and flux. This temperature is much lower than that of traditional methods. The x-ray powder diffraction patterns showed three strong peaks of diamond. The Raman spectrum showed a sharp peak at 1332 inverse centimeters, which is characteristic of diamond. Although the yield was only 2 percent, this method is a simple means of forming diamond.

Journal Article↗
PubMed1998

Preparation and characterization of an endogenously fluorescent annexin for detection of apoptotic cells.

Annexin proteins specifically bind anionic phospholipids such as phosphatidylserine, which are normally confined to the cytoplasmic leaflet of cellular membranes. During programmed cell death, or apoptosis, this phospholipid asymmetry is lost, and anionic phospholipids are exposed on the extracellular leaflet of the plasma membrane where they are accessible to exogenously added, labeled annexins. Chemically [e.g., fluoroscein isothiocyanate (FITC)]-modified annexin V has been widely used to detect and enumerate apoptotic cells by flow cytometry. We prepared chimeric proteins containing green fluorescent protein (GFP) fused to annexin V. A chimera containing GFP fused to the C-terminus of annexin V was soluble and fluorescent, but was unable to bind phospholipids. In contrast, a chimera containing GFP fused to the N-terminus of annexin V specifically bound apoptotic cells. GFP-annexin V represents a sensitive and facile alternative to FITC-annexin V for studies of apoptosis.

Animals↗
PubMed1998

[A study of genetic heterogeneity in Pfeiffer syndrome].

OBJECTIVE: To understand the molecular pathology of Pfeiffer syndrome. METHODS: DNA from peripheral blood was examined in 4 families with Pfeiffer syndrome by SSCP-sequence analyses and PCR-restriction enzyme digestion. RESULTS: The authors found the mutations of FGFR2 gene in two families, an A to G transition in the 3' acceptor splice site of intron 8 in a family, and Asp321 Ala substitution in exon 9 in another family. In addition, the mutation in exon 5 of FGFR1 gene (Pro252Arg) was found in a family. CONCLUSION: These findings reveal the genetic heterogeneity of Pfeiffer syndrome and can help one understand the molecular mechanism of the disease.

Acrocephalosyndactylia↗
PubMed1998

Tripeptide growth hormone secretagogues.

A series of C-terminus capped dipeptides and tripeptides was synthesized as growth hormone (GH) secretagogues. Among them, tripeptide Aib-D-Trp-D-homoPhe-OEt showed low nanomolar activity in the rat pituitary assay. Thus, we have demonstrated that the GH secretagogue activity of the hexa-hepta-GH releasing peptides can be mimicked at the tripeptide level.

Amino Acid Sequence↗
PubMed1998

Intercellular communication mediates the bystander effect during herpes simplex thymidine kinase/ganciclovir-based gene therapy of human gastrointestinal tumor cells.

A bystander effect is described when nontransduced or genetically unmodified cells are killed during death of genetically modified tumor cells transduced with a suicide gene. The "bystander effect" greatly enhances the efficacy of the herpes simplex virus-thymidine kinase/ganciclovir (HSV-TK/GCV) gene therapy approach for cancer. The mechanism of the bystander effect is controversial. In this study, we examined the role of intercellular gap junction communication (GJIC) for the bystander effect in human gastrointestinal tumor cells. Our results show that the extent of the bystander effect varied amongst the tumor cell lines; pancreatic cancer cells BXPC-3 exhibited excellent bystander effects in vitro and in vivo studies whereas other gastrointestinal tumor cell lines such as pancreatic cancer cells MIAPACA-2, and colon cancer cells HT-29 showed poor bystander effects. Bystander effects were only found in the presence of cell-to-cell contact. The extent of the bystander effect was independent of the level of HSV-TK activity in the transduced tumor cells and was correlated with GJIC as demonstrated by an in vitro dye-transfer assay. Expression of the mRNA levels of gap junction protein connexin 43 was 8- to 26-fold or greater and connexin 26 gene expression was 2- to 229-fold greater in BXPC-3 cells compared to HT-29, MIAPACA-2, and PANC3 cells. Our results suggest that intercellular communication is essential for the bystander effect. The correlation between GJIC and the extent of the bystander effect suggest a role for GJIC in mediating the bystander effect. Analysis of tumors for GJIC or expression of gap junction proteins may identify the subset of patients suitable for gene therapy with the HSV-TK/GCV approach.

Animals↗
PubMed1998

Transforming growth factor-beta stimulates interleukin-11 transcription via complex activating protein-1-dependent pathways.

Studies were undertaken to characterize the mechanism by which transforming growth factor-beta1 (TGF-beta1) stimulates epithelial cell interleukin (IL)-11 production. Nuclear run-on studies demonstrated that TGF-beta1 is a potent stimulator of IL-11 gene transcription. TGF-beta1 also stimulated the luciferase activity in cells transfected with reporter gene constructs containing nucleotides -728 to +58 of the IL-11 promoter. Studies with progressive 5' deletion constructs and site-specific mutations demonstrated that this stimulation was dependent on 2 AP-1 sites between nucleotides -100 and -82 in the IL-11 promoter. Mobility shift assays demonstrated that TGF-beta1 stimulated AP-1 protein-DNA binding to both AP-1 sites. Supershift analysis demonstrated that JunD was the major moiety contributing to AP-1-DNA binding in unstimulated cells and that c-Jun-, Fra-1-, and Fra-2-DNA binding were increased whereas JunD-DNA binding was decreased in TGF-beta1-stimulated cells. The sequence in the IL-11 promoter that contains the AP-1 sites also conferred TGF-beta1 responsiveness, in a position-independent fashion, on a heterologous minimal promoter. Thus, TGF-beta1 stimulates IL-11 gene transcription via a complex AP-1-dependent pathway that is dependent on 2 AP-1 motifs between nucleotides -100 and -82 that function as an enhancer in the IL-11 promoter.

Base Sequence↗
PubMed1998

Potent 3-spiropiperidine growth hormone secretagogues.

Systematic SAR studies of the different regioisomers and homologues of the spiro(indane-1,4-piperidine) moiety in the growth hormone secretagogue L-162,752 are presented. Among them, spiro(3H-1-benzopyran-2,3-piperidine) was found to afford secretagogues with low nanomolar in vitro activity.

Animals↗
PubMed1998

Neuroprotective effects of creatine and cyclocreatine in animal models of Huntington's disease.

The gene defect in Huntington's disease (HD) may result in an impairment of energy metabolism. Malonate and 3-nitropropionic acid (3-NP) are inhibitors of succinate dehydrogenase that produce energy depletion and lesions that closely resemble those of HD. Oral supplementation with creatine or cyclocreatine, which are substrates for the enzyme creatine kinase, may increase phosphocreatine (PCr) or phosphocyclocreatine (PCCr) levels and ATP generation and thereby may exert neuroprotective effects. We found that oral supplementation with either creatine or cyclocreatine produced significant protection against malonate lesions, and that creatine but not cyclocreatine supplementation significantly protected against 3-NP neurotoxicity. Creatine and cyclocreatine increased brain concentrations of PCr and PCCr, respectively, and creatine protected against depletions of PCr and ATP produced by 3-NP. Creatine supplementation protected against 3-NP induced increases in striatal lactate concentrations in vivo as assessed by 1H magnetic resonance spectroscopy. Creatine and cyclocreatine protected against malonate-induced increases in the conversion of salicylate to 2,3- and 2,5-dihydroxybenzoic acid, biochemical markers of hydroxyl radical generation. Creatine administration protected against 3-NP-induced increases in 3-nitrotyrosine concentrations, a marker of peroxynitrite-mediated oxidative injury. Oral supplementation with creatine or cyclocreatine results in neuroprotective effects in vivo, which may represent a novel therapeutic strategy for HD and other neurodegenerative diseases.

Adenosine Triphosphate↗
PubMed1998

Mechanisms of long-term donor-specific allograft survival induced by pretransplant infusion of lymphocytes.

Pretransplantation donor-specific transfusion (DST) can enhance allograft survival in man and animals. However, due to the lack of a specific marker to identify donor-reactive cells in vivo in man and normal (nontransgenic) animals, the underlying mechanism remains unknown. In this study, we use 2CF1 transgenic mice expressing a transgenic T-cell receptor (TCR) specifically recognizing Ld, a major histocompatibility complex (MHC) class I molecule, to delineate the role of DST in long-term skin allograft survival and its underlying mechanisms. Our main findings include: (1) in the absence of any other immunosuppressive treatment, a single dose pretransplantation infusion of viable splenocytes from an Ld+ donor is sufficient to induce permanent donor-specific skin allograft survival in 2CF1 anti-Ld TCR transgenic mice; (2) DST leads to a deletion of the majority (>60%) of donor-reactive T cells in the periphery of the recipient. However, deletion does not necessarily result in tolerance; (3) remaining donor-reactive T cells from DST-treated mice are fully responsive to Ld in vitro, and can suppress the antidonor response of naive T cells in vitro only when exogenous interleukin (IL)-4 is provided; and (4) the sera level of IL-4 in DST-treated tolerant mice is significantly increased. These results suggest that the generation of a subset of T cells with the potential to specifically inhibit antidonor responses, together with promotion of IL-4 production in recipients, may be important mechanisms for the induction and maintenance of antigen-specific tolerance.

Animals↗
PubMed1998

Corticosteroid therapy does not alter the threshold for contraction-induced injury in dystrophic (mdx) mouse diaphragm.

The effects of methylprednisolone therapy on the susceptibility of dystrophin-deficient myofibers to contraction-induced injury were evaluated in the mdx mouse diaphragm model of Duchenne dystrophy. Mdx myofibers were abnormally vulnerable to injury induced by high-stress eccentric contractions. However, methylprednisolone therapy did not significantly alter the degree of contraction-induced injury. These data suggest that beneficial effects of corticosteroid therapy in Duchenne dystrophy are unlikely to be related to a change in the threshold for contraction-induced myofiber damage.

Adrenal Cortex Hormones↗
PubMed1998

Human magnetic resonance imaging at 8 T.

In this work, we present the first human magnetic resonance image (MRI) obtained at ultrahigh field strengths (8 T). We demonstrate that clinical imaging will be possible at 8 T and that reasonable quality head images can be obtained at this field strength. Most importantly, we emphasize that the power required to excite the spins at 8 T is much lower than had previously been predicted by the nuclear magnetic resonance theory. A 90 degree pulse in the head at 8 T requires only approximately 0.085 J of energy (90 W for a 2-lobe 4 ms sinc pulse). Based on measurements at 4 T, 1-2 J of energy should have been utilized to achieve a 90 degree excitation at 8 T. The fact that the energy required for spin excitation at 8 T is much lower than predicted by the NMR theory, will be extremely important to the viability of ultrahigh field imaging, since concerns related to power absorption and specific absorption rate (SAR) violations at ultrahigh field are alleviated. As such, it will be possible to utilize RF intensive pulse sequences and adiabatic spin excitation at 8 T without significant risk to the subject.

Brain↗
PubMed1998

High resolution analysis of protein phosphorylation using capillary isoelectric focusing - electrospray ionization - mass spectrometry.

On-line capillary isoelectric focusing (CIEF)-electrospray ionization - mass spectrometry (ESI-MS) as a two-dimensional separation system is employed for high resolution analysis of ovalbumin phosphorylation. On the basis of their differences in isoelectric point (pI), the mono- and diphosphoovalbumins are separated and resolved in CIEF. The focused protein zones of mono- and diphosphoovalbumins are eluted by combining gravity with cathodic mobilization. At the end of the CIEF capillary, the mobilized ovalbumin zones are analyzed by mass spectrometry coupled on-line to an electrospray interface with a coaxial sheath flow configuration. Additional ovalbumin variants within each of the mono- and diphosphoovalbumins, differing in their molecular masses due to glycosylation microheterogeneity, are easily distinguished by ESI-MS.

Electrophoresis, Capillary↗
PubMed1998

Azulenyl nitrone spin traps protect against MPTP neurotoxicity.

Azulenyl nitrones are a unique class of free radical spin-trapping compounds. We administered both a water-soluble and a lipid-soluble azulenyl nitrone to mice prior to administration of MPTP. Both compounds produced significant neuroprotection against depletions of dopamine and its metabolites measured 1 week after MPTP administration. There were no effects on MPP+ levels. These findings provide further evidence that free radical scavengers can produce significant neuroprotection against MPTP neurotoxicity.

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