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Biomedical subjects

L Yang

Publications and source records attributed to L Yang.

At least 433 records · Page 24Linked to original sources
PubMed1998

Manganese superoxide dismutase overexpression attenuates MPTP toxicity.

There is substantial evidence implicating mitochondrial dysfunction and free radical generation in the neurotoxicity of MPTP. Manganese superoxide dismutase (MnSOD) is the primary antioxidant enzyme protecting against superoxide radicals produced within mitochondria. Overexpression of human MnSOD in transgenic mice resulted in increased MnSOD localized to mitochondria in neurons and a 50% increase in total MnSOD activity in brain homogenates. We found that MPTP toxicity was significantly attenuated in the MnSOD transgenic mice which overexpress the human manganese superoxide dismutase gene, with these mice showing threefold greater dopamine levels than controls following MPTP. There were no alterations in MPP+ levels, suggesting that the effects were not due to altered metabolism of MPTP. A significant increase in 3-nitrotyrosine levels was seen in littermate controls but not in transgenic mice overexpressing human MnSOD. These results provide further evidence implicating mitochondrial dysfunction and oxidative damage in the pathogenesis of MPTP neurotoxicity.

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

Ubiquitin immunoreactivity of paired helical filaments differs in Alzheimer's disease and corticobasal degeneration.

To establish whether there is a relationship between ubiquitination and ultrastructural appearance of filaments, we compared the ubiquitin immunoreactivity of paired helical filaments (PHFs) in Alzheimer's disease (AD) and corticobasal degeneration (CBD). PHFs in these disorders share a limited similarity since filaments in CBD are wider and twisted at longer intervals than those in AD, and also display less ultrastructural stability. Preparations enriched in SDS-soluble filaments were isolated from AD and CBD brains and subjected to tau and ubiquitin immunogold labeling. Both preparations contained mostly dispersed individual PHFs, which labeled for the amino and carboxyl termini of tau. Immunolabeling of ubiquitin was variable, however, being more intense in AD than CBD samples. SDS-insoluble filaments were prepared from PHFs by boiling in the presence of SDS and 2-mercaptoethanol and collected by sedimentation. In both disorders, the pellets contained highly aggregated and bundled filaments, which were devoid of the amino but not the carboxyl terminal region of tau. Again, ubiquitin labeling was more intense in AD than CBD filaments. The present results suggest that ubiquitination has limited influence on SDS solubility, aggregation and bundling of PHFs; however, it may be one of the factors responsible for the ultrastructural variability and/or stability of filaments.

Aged↗
PubMed1998

Linkage between atopy and the IgE high-affinity receptor gene at 11q13 in atopic dermatitis families.

Atopic dermatitis is a common skin disease frequently associated with allergic disorders such as allergic rhinitis and asthma. Controversial linkage findings between atopy and markers at chromosome 11q13 led us to search chromosome 11 for genes conferring susceptibility to atopic dermatitis and atopy. Twelve families were investigated using highly polymorphic markers and a powerful model-free linkage test. Two markers gave evidence for linkage, D11S903 (P = 0.02) and FCER1B (P = 0.005). A two-point lod-score analysis between these two markers revealed significant evidence for linkage (zmax = 4.02 at (theta = 0.0). In regard to model-dependent lod-score analyses between atopic disorders and FCER1B, two-point analysis gave a lod score of z = 0.78 whereas two-locus analysis using a recessive-dominant mode of inheritance displayed a significant lod score of z = 3.55. Only 2 of 12 families showed evidence for linkage using the latter oligogenic model. In conclusion, the results of our study map the FCER1B gene in close proximity to D11S903, support the finding of Cookson et al. implicating the IgE high-affinity receptor gene (FCER1B) at 11q13, and furthermore suggest an oligogenic mode of inheritance as well as heterogeneity in the genetic susceptibility to atopy and atopic dermatitis.

Adolescent↗
PubMed1998

Neutron off-plane scattering of aligned membranes. I. Method Of measurement.

We describe a method of measuring neutron scattering of aligned membranes with the momentum transfer oriented parallel or partly perpendicular to the plane of the membranes. The method obtains the complete information for the structures within fluid membranes obtainable by scattering. Data from alamethicin- and magainin-induced pores are presented. Although the in-plane scattering curves of these two peptides are similar to each other, their off-plane scattering patterns are strikingly distinct. Magainin pores exhibit intermembrane correlations.

Alamethicin↗
PubMed1998

Brain natriuretic peptide enhances the endothelium-independent cAMP and vasorelaxant responses of calcitonin gene-related peptide in rat aorta.

Calcitonin gene-related peptide (CGRP) causes vasorelaxation in rat aorta involving endothelium/nitric oxide (NO)-dependent elevations of both cAMP and cGMP levels. When endothelium is removed, preincubation with exogenous NO uncovers and potentiates direct (endothelium-independent) cAMP elevations and vasorelaxations caused by CGRP. This enhancing effect of NO potentially involves elevation of cGMP and inhibition of Type III (cGMP-inhibitable) phosphodiesterase, causing accumulation of cAMP. However, NO may have other actions. The aim of the present study was to determine if brain natriuretic peptide (BNP), which elevates cGMP levels independent of NO, could enhance cAMP accumulations and vasorelaxations induced by CGRP in rat aortic rings denuded of endothelium. When added separately, neither CGRP (100 nM) nor BNP (10 nM) altered cAMP levels. When added in combination, CGRP (100 nM) and BNP (10 nM) significantly elevated cAMP levels (from control of 0.95+/-0.08 to 1.53+/-0.09 pmol/mg protein) at 2 min. BNP (10 nM) elevated cGMP levels 10-fold at 2 min and this response was not altered by co-administration of CGRP (100 nM). Pretreatment with BNP at concentrations as low as 1 nM in endothelium-denuded aortic rings greatly enhanced the direct vasorelaxant effects of CGRP (100 nM) (from control of 0% to 57.6+/-6.8% relaxation of phenylephrine-precontractions). Our findings indicate that BNP enhances direct (endothelium-independent) cAMP elevations and vasorelaxations caused by CGRP in rat aorta, thus supporting the concept that cGMP inhibits cAMP metabolism and enhances CGRP-induced responses in aortic smooth muscle cells.

Animals↗
PubMed1998

CYP21 pseudogene transcripts are much less abundant than those from the active gene in normal human adrenocortical cells under various conditions in culture.

The human steroid 21-hydroxylase pseudogene (CYP21P, also termed CYP21A) is transcribed in the adrenal cortex, but the relative abundance of transcripts from CYP21P and from the active CYP21 gene (also termed CYP21B) is not well established. In the present experiments we cultured primary human adrenocortical cells in defined medium and used RNase protection assays to examine whether there might be a selective increase in the relative abundance of CYP21P transcripts under any of the various regulatory factors known to affect expression of 21-hydroxylase. Differences between the sequences of intron 2 in CYP21P and CYP21 allowed the synthesis of gene-specific probes spanning exon 3 and parts of the adjacent introns. CYP21- and CYP21P-specific probes spanning the site of the start of transcription were also synthesized. CYP21 transcripts were readily detectable. In agreement with previous observations on 21-hydroxylase mRNA and enzyme activity in primary cultures of human adrenocortical cells, the abundance of CYP21 transcripts was increased by cyclic AMP analogues (N6-monobutyryl cyclic AMP and 8-bromo cyclic AMP), insulin, IGF-I and tetradecanoyl phorbol acetate (TPA). However, CYP21P transcripts were not detected in the presence of any of the various regulatory factors known to affect expression of 21-hydroxylase.

Adrenal Cortex↗
PubMed1998

Successful recovery of 14 patients afflicted with full-thickness burns for more than 70 per cent body surface area.

Fourteen cases suffering full-thickness burns of more than 70 per cent total body surface area (TBSA) have been successfully treated during the last 8 years (1988-1995). Among these patients, 10 cases suffered from burns of more than 90 per cent TBSA. Five cases had full-thickness burns of 80-90 per cent TBSA. Escharectomy, followed by coverage of wounds with a homograft to the lower surface of which, adjacent to the wound bed, microautoskin grafts had been attached was employed to close wounds in the early stages after burn. The remaining non-surgically treated wound was treated by exposure and topical silver sulfadiazine. The temperature and humidity of the ward was controlled by air conditioning and dehumidification. Aggressive excision of eschar and auto-skingrafting was carried out 3 weeks post-injury. Strictly limiting the uncovered wound to less than 5 per cent appeared to be the major effective measure in preventing burn infection.

Administration, Topical↗
PubMed1998

Features of ipsilaterally evoked inhibition in the dorsal nucleus of the lateral lemniscus.

The dorsal nucleus of the lateral lemniscus (DNLL) is a binaural nucleus whose neurons are excited by stimulation of the contralateral ear and inhibited by stimulation of the ipsilateral ear. Here we report on several features of the ipsilaterally evoked inhibition in 95 DNLL neurons of the mustache bat. These features include its dependence on intensity, its tuning and the types of stimuli that are capable of evoking it. Inhibition was studied by evoking discharges with the iontophoretic application of glutamate, and then evaluating the strength and duration of the inhibition of the glutamate evoked background activity produced by stimulation of the ipsilateral ear. Excitatory responses were evoked by stimulation of the contralateral ear with best frequency (BF) tone bursts. Glutamate evoked discharges could be inhibited in all DNLL neurons and the inhibition often persisted for periods ranging from 10 to 50 ms beyond the duration of the tone burst that evoked it. The duration of the persistent inhibition increased with stimulus intensity. Stimulus duration had little influence on the duration of the persistent inhibition. Signals as short as 2 ms suppressed discharges for as long as 30 ms after the signal had ended. The frequency tuning of the total period of inhibition and the period of persistent inhibition were both closely matched to the tuning evoked by stimulation of the contralateral ear. Moreover, the effectiveness of complex signals for evoking persistent inhibition, such as brief FM sweeps and sinusoidally amplitude and frequency modulated signals, was comparable to that of tone bursts at the neuron's excitatory BF, so long as the complex signal contained frequencies at or around the neuron's excitatory BF. We also challenged DNLL cells with binaural paradigms. In one experiment, we presented a relatively long (40 ms) BF tone burst of fixed intensity to the contralateral ear, which evoked a sustained discharge, and a shorter, 10 ms signal of variable intensity to the ipsilateral ear. As the intensity of the 10 ms ipsilateral signal increased, it generated progressively longer periods of persistent inhibition and thus the discharges were suppressed for periods far longer than the 10 ms duration of the ipsilateral signal. With interaural time disparities, ipsilateral signals that led contralateral signals evoked a persistent inhibition that suppressed the responses to the trailing contralateral signals for periods of a least 15 ms. This suggests that an initial binaural sound that favors the ipsilateral ear should suppress the responses to trailing sounds that normally would be excitatory if they were presented alone. We hypothesize a circuit that generates the persistent inhibition and discuss how the results with binaural signals support that hypothesis.

Acoustic Stimulation↗
PubMed1998

Induction of new bone by ceramic bovine bone with recombinant human bone morphogenetic protein 2 and transforming growth factor beta.

Bone morphogenetic protein (BMP) has the ability to induce ectopic bone, while the action of transforming growth factor beta (TGF beta) is to stimulate proliferation of osteoblasts and chondrocytes as well as the production of extracellular matrix. The aim of the present study was to study their synergistic actions in bone formation. Three kinds of complexes, recombinant human BMP2 (rhBMP2), TGF beta and rhBMP2/TGF beta in ceramic bovine bone (CBB), were made and then implanted into the thigh muscle pouches of mice. The histological reactions of the implanted areas were studied at intervals of 3, 5, 7, 14 and 21 days. The results showed that, except for the implants with TGF beta alone, both rhBMP2 and rhBMP2/TGF beta implants exhibited new ectopic bone formation. The morphometric study revealed that the quantity of newly formed bone induced by rhBMP2/TGF beta was obviously greater than by rhBMP2 alone. These results indicate that TGF beta in combination with BMP may enhance formation of ectopic bone.

Animals↗
PubMed1998

Transjugular intrahepatic portosystemic shunt in a porcine model: histologic characteristics at the early stage.

RATIONALE AND OBJECTIVES: The authors attempted to determine the histologic processes that take place during development of stenosis after transjugular intrahepatic portosystemic shunt (TIPS) creation. MATERIALS AND METHODS: TIPS were created with metallic stents in 20 healthy domestic pigs (tantalum stents in 10, stainless steel stents in 10). The animals were sacrificed 2-16 days later. All the shunts were examined by means of venography both immediately after placement of the stents and before sacrifice. All histologic sections were assessed with modified Giemsa and basic fuchsin stains. Anti-smooth-muscle-cell alpha-actin stain was used in three specimens. The stenotic reaction was quantified by using standard planimetry techniques and a computerized image-analysis system. RESULTS: Within 16 days after TIPS placement, 15 (75%) of the 20 shunts were completely occluded, four (20%) of 20 shunts were partially occluded, and one (5%) of 20 shunts remained widely patent (animal died of unknown cause 2 days after the TIPS procedure). Stent occlusion was caused primarily by pseudointimal hyperplasia, which was similar morphologically in the portal, middle, and hepatic portions of the stent. Myofibroblastic proliferation was the most striking feature of the pseudointimal hyperplasia. The average thickness of the proliferation was 2.14 mm, which was 67% of the total diameter of the stent. A mild fibrous or lymphocytic reaction occurred around the stent wires and between the pseudointimal hyperplasia and the liver parenchyma. CONCLUSION: The histologic features of pseudointimal formation in this swine TIPS model closely resemble those in humans. This model may prove useful for evaluating stents and other devices and improving the understanding of restenosis after vascular interventions.

Animals↗
PubMed1998

Adenovirus-mediated dystrophin minigene transfer improves muscle strength in adult dystrophic (MDX) mice.

Duchenne muscular dystrophy (DMD) and murine X-linked muscular dystrophy (mdx) are both due to absence of the subsarcolemmal protein dystrophin. Recombinant adenovirus vectors (AdV) are considered a promising means for delivering a functional dystrophin gene to muscle. However, the usefulness of AdV for this purpose is limited by vector toxicity as well as immune-mediated elimination of infected fibers. In addition, studies to date of AdV-mediated dystrophin gene transfer have either failed to examine effects on muscle strength or been performed in immunologically immature neonatal animals with little baseline abnormality of force-generating capacity. In the present study, AdV-mediated dystrophin gene transfer was performed in adult mdx mice with pre-existent dystrophic pathology and muscle weakness. The main findings are as follows: (1) acute myofiber toxicity and gene transfer efficiency are both AdV dose-dependent, such that the therapeutic margin of safety is fairly narrow; (2) immunosuppressive therapy (FK506) prevents immune-mediated elimination of dystrophin-positive fibers but not the dose-dependent toxic effects; (3) at the optimal vector dosage and with effective immunosuppression, AdV-mediated dystrophin minigene transfer is capable of alleviating the loss of force-generating capacity as well as histopathological evidence of disease progression normally seen in adult mdx muscles over a 2-month period. These findings have important implications for the eventual application of AdV-mediated dystrophin gene transfer in DMD patients.

Adenoviridae↗
PubMed1998

Effect of selective substitution of 5-bromocytosine on conformation of DNA triple helices.

Three triplex DNAs containing 5-bromocytosine[BrC] were studied by vibrational spectroscopy and molecular modelling. Firstly, three oligodeoxypyrimidines of 5'-(TC)3-T4-(BrCT)3 [CBrC], 5'-(TBrC)3-T4-(CT)3 [BrCC] and 5'-(TBrC)3-T4-(BrCT)3 [BrCBrC] were synthesized and then reacted with an oligodeoxypurine of 5'-(AG)3 at pH=4.5 in phosphate buffer respectively to form three comparative hairpin triplex named CY,YC and YY. The results of FT-Raman and IR revealed that YY is almost in A-like form, CY and YC are combinations of A-like form and B-like form, but A-form dominates in CY while B-form is equivalent as A-form in YC. The result is consistent with the theoretical analysis.

Cytosine↗
PubMed1998

Effect of plasmid DNA on immunogenicity of HBsAg-anti-HBs complex.

Hepatitis B surface antigen (HBsAg) complexed with anti-HBs is more immunogenic than HBsAg alone in mice. This complex is usually used with alum as an adjuvant, which can enhance humoral response but inhibits cell-mediated immune responses. To improve the immunogenicity of HBsAg-anti-HBs, we immunized mice with a combination of this immunogenic complex and pCMVHBs, a plasmid encoding HBsAg, or the vector pCMV. Both plasmids enhanced the anti-HBs response induced by the immunogenic complex. We found 20 microg of plasmid or vector enhanced the anti-HBs response in all mice, whereas 1 microg was less effective. Splenocytes from different immunized groups were stimulated with HBsAg in vitro, and the highest level of IL-2 detected in the supernatant was found in mice immunized with HBsAg-anti-HBs plus pCMVHBs. A plasmid (pcDNA3c191) encoding core protein of hepatitis C virus (HCV) was used as an adjuvant to the immunogenic complex. A preliminary result showed that pcDNA3c191 not only enhanced the immunogenicity of HBsAg-anti-HBs, but also induced anti-HCV core antibodies. Immunization using a plasmid DNA encoding one viral antigen in combination with antigen and antibody complex of another microbial origin could be a new approach to the development of multivalent vaccines.

Animals↗
PubMed1998

Differential expression of urinary inter-alpha-trypsin inhibitor trimers and dimers in normal compared to active calcium oxalate stone forming men.

PURPOSE: We determine if the immunoreactive profile of urinary inter-alpha-trypsin inhibitor can be used to distinguish between normal individuals and individuals with calcium oxalate stone disease. MATERIALS AND METHODS: Urinary proteins were dialyzed against water (15 kDa. molecular weight cutoff), lyophilized and resolved by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (6% acrylamide, reducing conditions) followed by Western blot. Inter-alpha-trypsin immunoreactive proteins were detected by enhanced chemiluminescence. Stone formation was confirmed to be active radiologically or passed as stone or gravel within 12 months of the sample. Stone composition was confirmed crystallographically. Normal individuals had no personal or familial history of urolithiasis and matched stone forming patients regarding race (white) and age (23 to 71 years old). Urine from a total of 101 individuals was analyzed. RESULTS: The intact inter-alpha-trypsin trimer (approximately 220 to 240 kDa.) and heavy chain (HC) 2-bikunin/HC1-bikunin dimers (approximately 115 to 130 kDa.) were detected more often in stone forming men (23 of 26 [89%] and 26 of 26 [100%], respectively) than in normal individuals (6 of 26 [23%] and 5 of 26 [19%], respectively, p < 0.0001). In those normal individuals who expressed inter-alpha-trypsin trimer and HC-bikunins the relative intensities were 5.3+/-1.4% and 16.3+/-17.1% of the stone forming controls, respectively. The identity of high molecular weight-inter-alpha-trypsin immunoreactive bands was confirmed using antibodies against the individual subunits (HC1, HC2, HC3, bikunin). In contrast to men high molecular weight-inter-alpha-trypsin's were readily detected in normal and stone forming women with equal frequency (inter-alpha-trypsin-trimer p=0.1337, HC-bikunins p=0.2836): inter-alpha-trypsin-trimer 17 of 18 [94%] and 9 of 13 [77%]; HC-bikunins 17 of 18 [94%] and 10 of 13 [85%]). Inter-alpha-trypsin-trimer and HC-bikunins, respectively, were detected in 2 and 5 of 10 patients with chronic renal disease. Expression was not related to hematuria or proteinuria. CONCLUSIONS: Immunoreactive profiles of urinary proteins may be able to be developed into a useful diagnostic tool to identify active stone formation, although a separate panel may be required for men and women. It is possible that these differences may provide clues as to why the incidence of stone disease is higher in men than women.

Adult↗
PubMed1998

Isolation and characterization of a group of oligopeptides related to oxidized glutathione from the root of Panax ginseng.

Six gamma-glutamyl oligopeptides were isolated for the first time from aqueous methanol extracts of Panax ginseng root by using column chromatography on ion-exchange resin, gel filtration and reverse-phase high-performance liquid chromatography. Their structures had been established with the methods of amino acid analysis, N-terminal, C-terminal determination and double-coupling sequence analysis. They were: P-I (N-gamma-glutamylcystinyl-bis-glycine), P-ll (gamma-glutamylcysteinylglycine disulfide, oxidized glutathione), P-III (N,N'-bis-gamma-glutamylcystinylglycine), P-IV (gamma-glutamylcysteinylglycinamide disulfide), P-V (N-gamma-glutamylglycylcysteine disulfide), P-VI(gammaglutamylarginine); five of them are related to oxidized glutathione. The structures were further confirmed by the chemical synthesis. As far as we know, P-V (N-gamma-glutamylglycylcysteine disulfide) is a new biologically active peptide which exhibits somnogenic effect and is more potent than that of P-II.

Amino Acids↗
PubMed1998

Inhibition of PrKX, a novel protein kinase, and the cyclic AMP-dependent protein kinase PKA by the regulatory proteins of adeno-associated virus type 2.

Adeno-associated virus encodes four nonstructural proteins, which are known as Rep78, Rep68, Rep52, and Rep40. Expression of these nonstructural proteins affects cell growth and gene expression through processes that have not yet been characterized. Using a yeast two-hybrid screen, we have demonstrated that a stable interaction occurs between the viral proteins Rep78 and Rep52 and the putative protein kinase PrKX, which is encoded on the X chromosome. The stability and specificity of the Rep-PrKX interaction were confirmed by coimmunoprecipitation of complexes assembled in vitro and in vivo. Overexpressed PrKX, which was purified from cos cells, was shown to phosphorylate a synthetic protein kinase A (PKA) substrate. However, this activity was dramatically inhibited by stoichiometric amounts of Rep52 and weakly inhibited with Rep68, which lacks the carboxy-terminal sequence contained in Rep52. Similarly, a stable interaction was observed with Rep78, which also contains the carboxy-terminal sequence of Rep52. A stable interaction and inhibition were also observed between Rep52 and the catalytic subunit of PKA. By using surface plasmon resonance and kinetic studies, Kis of approximately 300 and 167 nM were calculated for Rep52 with PKA and with PrKX, respectively. Thus, Rep52 but not Rep68 can significantly inhibit the trans- and autophosphorylation activities of these kinases. The biological effects of Rep78-specific inhibition of PKA-responsive genes are illustrated by the reduction of steady-state levels of cyclic AMP-responsive-element-binding protein and cyclin A protein.

Amino Acid Sequence↗