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Biomedical subjects

W Yuan

Publications and source records attributed to W Yuan.

At least 91 records · Page 5Linked to original sources
PubMed1999

Short term modification of disparity vergence eye movements.

Dynamics of disparity vergence eye movements can be modified by adaptive stimuli that generate large transient disparities. These modifications were observed for convergence as well as divergence eye movements. After modification, the peak velocities of the step responses for convergence and divergence were substantially higher than in normal baseline responses, a change observed in all four subjects studied. The change in peak velocity of a step response occurred very rapidly after presentation of the adaptive stimuli. Main sequence plots showed that first-order dynamic characteristics increased for post-adaptive responses with respect to normal step responses. Hence, response modification could be quantified as a change in gain accompanied with an increase in the effective response time constant. The adaptive responses to convergent and divergent 'disappearing' step stimuli revealed that the adaptation process modifies the high-velocity component of both disparity convergence and divergence eye movements. Moreover, a gain change in this component alone could account for both the gain and the time constant modifications seen in the overall response. A process of recovery or de-adaptation was also observed for both convergence and divergence eye movements. This observed short-term modification demonstrates a unique control mechanism for vergence eye movements that is effective in either direction.

Adaptation, Ocular↗
PubMed1999

Analgesic efficacy of the cyclooxygenase-2-specific inhibitor rofecoxib in post-dental surgery pain: a randomized, controlled trial.

Previous data have suggested that rofecoxib, a cyclooxygenase (COX)-2-specific inhibitor, had analgesic effects similar to those of the nonsteroidal anti-inflammatory drugs when tested in the post-dental surgery pain model. The objective of this parallel-group, double-masked, randomized, placebo- and active comparator-controlled clinical trial was to assess more fully the analgesic efficacy of rofecoxib in the treatment of postoperative dental pain. After dental surgery, 151 patients (50.3% women; mean age, 18.3 years; 93.4% white) experiencing moderate-to-severe pain were to receive a single dose of placebo, rofecoxib 50 mg, or ibuprofen 400 mg. Analgesic efficacy was assessed for up to 24 hours postdose using self-administered questionnaires. Tolerability was assessed using spontaneous reports of adverse experiences, physical findings, and laboratory measurements. The results of this study demonstrated that rofecoxib 50 mg was more effective than placebo on all measures of analgesic efficacy. Rofecoxib 50 mg exhibited overall analgesic effects, onset of analgesia, and peak analgesic effects that were not significantly different from those of ibuprofen 400 mg, with a significantly longer duration of action (P < 0.05). We concluded that rofecoxib was efficacious in the treatment of postoperative dental pain and that COX-2-derived prostanoids play a role in treatment of the pain associated with dental surgery.

Adolescent↗
PubMed1999

Stimulation of type I collagen transcription in human skin fibroblasts by TGF-beta: involvement of Smad 3.

Transforming growth factor-beta (TGF-beta) stimulates the transcription of the alpha2(I) procollagen gene (COL1A2). The intracellular mediators involved in this response remain poorly understood. In this study, we demonstrate that primary human skin fibroblasts express Smads, a novel family of signaling molecules, in vitro in the absence of TGF-beta. The levels of Smad 7 mRNA was rapidly and transiently increased by TGF-beta. Transient overexpression of Smad 3 and Smad 4, but not Smad 1 or Smad 2, caused trans-activation of a CAT reporter gene driven by a 772 bp segment of the human COL1A2 promoter containing putative TGF-beta response elements. Smad stimulation of promoter activity was ligand independent, but was further enhanced by TGF-beta. Overexpression of a phosphorylation-deficient Smad 3 mutant or wild-type Smad 7, which lacks the carboxy-terminal phosphorylation motif, specifically inhibited TGF-beta-induced activation of COL1A2 promoter. A CAGACA sequence shown to be a functional Smad-binding element in the plasminogen activator inhibitor-1 gene promoter was found within the TGF-beta-response region of the proximal COL1A2 promoter. Gel mobility shift assays showed protein phosphorylation-dependent binding activity in fibroblast nuclear extracts specific for this sequence; TGF-beta treatment strongly stimulated the formation of this DNA-protein complex. Smad was identified as a component of the CAGACA-binding transcription complex in TGF-beta-treated fibroblasts by antibody supershifting. These results demonstrate that (i) Smad 3 transmits TGF-beta signals from the receptor to the COL1A2 promoter in human fibroblasts, and is likely to play an important role in stimulation of COL1A2 promoter activity elicited by TGF-beta; (ii) in fibroblasts, Smads appear to function as inducible DNA-binding transcription factors; and (iii) Smad 7 may be involved in autocrine negative feedback in the regulation of COL1A2 promoter activity by TGF-beta.

Cells, Cultured↗
PubMed1999

Glucose-induced autophagy of peroxisomes in Pichia pastoris requires a unique E1-like protein.

Cytosolic and peroxisomal enzymes necessary for methanol assimilation are synthesized when Pichia pastoris is grown in methanol. Upon adaptation from methanol to a glucose environment, these enzymes are rapidly and selectively sequestered and degraded within the yeast vacuole. Sequestration begins when the vacuole changes shape and surrounds the peroxisomes. The opposing membranes then fuse, engulfing the peroxisome. In this study, we have characterized a mutant cell line (glucose-induced selective autophagy), gsa7, which is defective in glucose-induced selective autophagy of peroxisomes, and have identified the GSA7 gene. Upon glucose adaptation, gsa7 cells were unable to degrade peroxisomal alcohol oxidase. We observed that the peroxisomes were surrounded by the vacuole, but complete uptake into the vacuole did not occur. Therefore, we propose that GSA7 is not required for initiation of autophagy but is required for bringing the opposing vacuolar membranes together for homotypic fusion, thereby completing peroxisome sequestration. By sequencing the genomic DNA fragment that complemented the gsa7 phenotype, we have found that GSA7 encodes a protein of 71 kDa (Gsa7p) with limited sequence homology to a family of ubiquitin-activating enzymes, E1. The knockout mutant gsa7Delta had an identical phenotype to gsa7, and both mutants were rescued by an epitope-tagged Gsa7p (Gsa7-hemagglutinin [HA]). In addition, a GSA7 homolog, APG7, a protein required for autophagy in Saccharomyces cerevisiae, was capable of rescuing gsa7. We have sequenced the human homolog of GSA7 and have shown many regions of identity between the yeast and human proteins. Two of these regions align to the putative ATP-binding domain and catalytic site of the family of ubiquitin activating enzymes, E1 (UBA1, UBA2, and UBA3). When either of these sites was mutated, the resulting mutants [Gsa7(DeltaATP)-HA and Gsa7(C518S)-HA] were unable to rescue gsa7 cells. We provide evidence to suggest that Gsa7-HA formed a thio-ester linkage with a 25-30 kDa protein. This conjugate was not observed in cells expressing Gsa7(DeltaATP)-HA or in cells expressing Gsa7(C518S)-HA. Our results suggest that this unique E1-like enzyme is required for homotypic membrane fusion, a late event in the sequestration of peroxisomes by the vacuole.

Adaptation, Physiological↗
PubMed1999

Dynamics of the disparity vergence step response: a model-based analysis.

A new method to analyze the dynamics of vergence eye movements was developed based on a reconstruction of the presumed motor command signal. A model was used to construct equivalent motor command signals and transform an associated vergence transient response into an equivalent set of motor commands. This model represented only the motor components of the vergence system and consisted of signal generators representing the neural burst and tonic cells and a plant representing the ocular musculature and dynamics of the orbit. Through highly accurate simulations, dynamic vergence responses could be reduced to a set of five model parameters, each relating to a specific feature of the internal motor command. This dynamic analysis tool was applied to the analysis of inter-movement variability in vergence step responses. Model parameters obtained from a large number of response simulations showed that the width of the command pulse was tightly controlled while its amplitude, rising slope, and falling slope were less tightly regulated. Variation in the latter three parameters accounted for the most of the movement-to-movement variability seen in vergence step responses. Unlike version movements, pulse width did not increase with increased stimulus amplitude, although the other command signal parameters were substantially influenced by stimulus amplitude.

Computer Simulation↗
PubMed1999

Insulin-like growth factor-II mediates the steroidogenic and growth promoting actions of follicle stimulating hormone on human ovarian pre-antral follicles cultured in vitro.

FSH is important for ovarian antral follicle growth and steroidogenesis, processes in the human that are believed to be mediated by IGF-II. The objective of this study was to determine if human ovarian pre-antral follicles are also FSH- and IGF-II-responsive, since the clinical questions and mechanisms underlying the effects on the pre-antral follicle pool of exogenously administered gonadotropins for fertility therapy and elevated endogenous gonadotropins in the perimenopause remain unanswered. Class 2 preantral follicles were isolated from human premenopausal ovaries (n=6) and cultured in vitro with androstenedione and either no additives or with FSH or IGF-II. FSH (100 ng/mL) stimulated estradiol (E2) production by 3.58 +/- 0.4 fold over 48 hr, compared to controls without FSH. This effect was completely inhibited in the presence of the IGF-II antagonist, IGF binding protein-4 (IGFBP-4). IGF-II also stimulated E2 production by preantral follicles with doses as low as 1 ng/mL and within 24 hr of treatment. Maximal response of 3- to 9-fold above control was achieved with 100 ng/mL of IGF-II between 96-120 hr of culture. IGFBP-4 completely inhibited E2 production to basal levels. FSH stimulated IGF-II mRNA in pre-antral follicles about 4-fold, determined by RT-PCR. FSH also stimulated follicle growth, determined by light microscopy, 50-68% over 48 hr, compared to controls (P<0.001), a process that was inhibited in the presence of IGFBP-4. Cumulatively, these data support IGF-II as a mediator of FSH action on human preantral follicles.

Adult↗
PubMed1999

Role of growth hormone in development and maintenance of follicles and corpora lutea.

Growth hormone (GH) is a pituitary hormone that affects animal growth, metabolism, lactation, and reproduction. Many of the effects of GH are mediated by insulin-like growth factor I (IGF-I) which is synthesized in liver and ovary in response to GH. Insulin-like growth factor I synergizes with gonadotrophins (LH and FSH) to stimulate growth and differentiation of ovarian cells. There are species differences in the effects of GH in reproductive biology. In most species, ovarian follicles and corpora lutea are potential sites for GH action because the GH receptor is found within granulosal cells as well as corpora lutea. However, growth hormone does not control ovarian IGF-I in all species and, in ruminants, endocrine IGF-I from liver may be the principal mediator of GH action. In cattle, administration of GH increases the number of small antral ovarian follicles but does not increase the number of large antral (dominant) follicles. Growth hormone may antagonize some aspects of dominant follicular function because dominant follicles are shorter-lived in GH-treated cattle. The corpora lutea has increased growth and steroidogenesis in response to GH. Growth hormone-induced steroidogenesis in cultured granulosal and luteal cells depends on IGF-I release after GH treatment. Bovine and ovine granulosal cells do not release IGF-I in response to GH in vitro and, therefore, are less responsive to GH. These results demonstrate that GH is required for normal reproductive function in ruminant as well as nonruminant species.

Animal Nutritional Physiological Phenomena↗
PubMed1999

[Experimental study on the osteoradionerosis of jaw model of dogs with vascular corrosion casting].

OBJECTIVE: To study pathologic alterations of mandibular microvascular system in osteoradionecrosis of jaws (ORNJ) in order to disclose its pathologic mechanism. METHODS: The right maxillofacial regions of 10 dogs were exposed to cobalt-60 radiation with a total dose of 60-80 Gy and dental extraction were performed at 3, 6 months after radiation. The ORNJ was diagnosed by gross observation, X-ray film and histopathologic examination. Then, the vascular corrosion castings of jaws were implemented and investigated. RESULTS: At 12 months after radiation, 7 cases of ORNJ occured. It was discovered on the casting specimen that the continuity of inferior alveolar arteries remained intact except one case where the artery was obliterated due to lesion involvement. There were defects of vascular networks in the necrotic area with irregular capillaries proliferating in the periphery of lesions and around the inferior alveolar arteries, where x-ray examination showed new bone formation. CONCLUSION: Based on the experimental evidences, a new concept of pathogenesis of ORNJ is put forward: following the formation of "3-hypo" structures, local trauma-repairing process might induce capillary proliferation which bring about a large amount of mitotic death of endotheliocytes, the microcirculation failure takes place leading to ORNJ eventually.

Animals↗
PubMed1999

[Radiculopathy after cervical laminectomy].

OBJECTIVE: To investigate radiculopathy after multilevel laminectomy in patients with cervical compression myelopathy and underlying mechanism. METHODS: We retrospectively reviewed 287 consecutive patients with cervical compression myelopathy treated by multilevel cervical laminectomy and identified 37 patients (12.9%) with postoperative radiculopathy. There were 27 men and 10 women, with an average age of 56 years at time of surgery. The diagnosis was either cervical spondylosis (25 patients) or ossification of the posterior longitudinal ligament (12 patients). RESULTS: Radiculopathy was observed from 4 hours to 6 days after surgery. The most frequent patterns of paralysis were C(5) and C(6) root involvements of the motor-dominant type. All patients showed complete recovery in 2 weeks to 3 years (average, 5.4 months). Follow up results showed that the recovery rate was negatively related to the duration of complete recovery of postoperative radiculopathy (r = -0.832, P < 0.01) and the patients with spondylotic myelopathy had a significantly better clinical recovery rate than those with ossification of the posterior longitudinal ligament (t = 2.960, P < 0.01). CONCLUSIONS: Postoperative radiculopathy is complicated with posterior cervical decompression and associated with tethering effect upon the nerve root. More logical procedures for prevention of postoperative radiculopathy are decompression through an anterior decompressive procedure in conjunction with a spinal fusion, which may achieve stabilization and directly remove all of the anterior spinal cord compression at multiple levels.

Adult↗
PubMed1999

[Protective effect of endothelin receptor subtype A antagonist BQ610 on the ultrastructure of acute ischemic myocardium in cats].

OBJECTIVE: To observe the effects of endothelin receptor subtype A antagonist BQ610 on acute ischemic myocardial injury by electronic microscopy to study whether endogenous endothelin is involved in the pathogenesis of acute myocardial ischemia. METHODS: Acute myocardial ischemia was induced by ligation of the left anterior descending coronary artery (LAD) in 12 cats, and BQ610 was immediately injected into the occluded LAD. Controls received normal saline (NS) injection. The ultrastructure of ischemic myocardium and non-ischemic myocardium were observed 30 min after LAD ligation. RESULTS: As compared wtih NS controls, BQ610 significantly protected the acute ischemic myocardium from ultrastructural injury, including cardiac muscle fiber swelling, myofibril disorganization and breakdown, mitochondrial swelling and endothelial swelling. In general, the non-ischemic myocardial ultrastructure was normal. CONCLUSIONS: The results indicate that endogenous endothelin, through endothelin receptor subtype A, plays an important role in ultrastructure injury of acute ischemic myocardium in cats.

Acute Disease↗
PubMed1999

[Analysis of mathematical model parameters for continuous rotary annular chromatography].

The curves of analysis solution of mathematical model for continuous rotary annular chromatography (CAC) coincide with experimental results well, but some points are derived from theoretical values due to the errors from experimental method. The width and the angles of maximum mass concentration solution at outlet (retention number), except for the other experimental conditions, depend on phase equilibrium coefficient and transfer functions. Because the precision of model parameters is strongly affected by the correction of experimental method, the sensitivities of phase equilibrium coefficients and transfer functions have been studied, in which the phase equilibrium coefficient is the key parameters to improve the separation effect of CAC process.

Biotechnology↗
PubMed1999

[A study on the treatment of congenital velopharyngeal insufficiency].

OBJECTIVE: To evaluate the effectiveness of speech therapy after pharyngoplasty in patients with congenital velopharyngeal insufficiency (CVPI). METHODS: Seven patients with CVPI had received pharyngoplasty and speech therapy. The blowing test and the Chinese articulation clear degree test were measured before and after speech therapy. RESULTS: The treatment results of seven patients appeared to be reasonably satisfactory after speech therapy. Both the index of blowing test and the Chinese articulation clear degree test increased significantly after speech therapy. CONCLUSION: Pharyngoplasty combined with speech therapy is effective in the treatment of patients with CVPI.

Child↗
PubMed1998

Evidence that NMDA receptors mediate the responses of putative RVLM presympathetic neurons to vagal afferent stimulation in rats.

Experiments were performed in 25 urethane-anaesthetized male Sprague-Dawley rats. Forty-six RVLM neurons were identified as putative presympathetic neurons according to their arterial baroreceptor reflex related properties, i.e. they were inhibited by stimulation of the aortic nerve; silenced by elevation of blood pressure and had a cardiac cycle related rhythm of spontaneous discharge. Responses of these neurons to tripled square wave stimulation of vagal afferents was tested by means of peristimulus time histograms. In addition to a long-lasting inhibition (I2), some neurons had one (P0) or two excitatory peaks (P1 and P2), and there was a short-lasting inhibition (I1) between P1 and P2. After microinjection of CPP (0.1 microl, 50 mM) into the NTS, the inhibitory responses were blocked, but the excitatory peaks were not affected; in the CVLM, CPP microinjection of the same dose had a similar effect on the responses elicited by vagal afferent stimulation in 15 of the 24 neurons tested. No detectable effects were observed in 9 neurons. However, intravenously administered ketamine attenuated or abolished these responses, either inhibitory or excitatory, in a dose dependent way. These results suggest: (1) an NMDA mechanism is involved in both the inhibitory and the excitatory responses. For the inhibitory responses, the involvement is both in the NTS and in the CVLM; for the excitatory responses, it is probably in the RVLM. (2) There may be a direct excitatory amino acid (EAA) pathway from the NTS to the RVLM.

Animals↗
PubMed1998

Discovery of a novel series of potent and selective substrate-based inhibitors of p60c-src protein tyrosine kinase: conformational and topographical constraints in peptide design.

On the basis of the efficient substrate for p60c-src protein tyrosine kinase (PTK) YIYGSFK-NH2 (1) (Km = 55 microM) obtained by combinatorial methods, we have designed and synthesized a series of conformationally and topographically constrained substrate-based peptide inhibitors of this enzyme, which showed IC50 values in the low-micromolar range (1-3 microM). A "rotamer scan" was performed by introducing the four stereoisomers of beta-Me(2')Nal in the postulated interaction site of the peptide inhibitor 23(IC50 = 1.6 microM). This substitution led to selective and potent inhibitors of p60c-src PTK; however, no substantial difference in potency was observed among them. This and the results of the "stereochemical scan" performed at residues 2 and 7 of 3 (peptides 19-21), which form the disulfide bond, may suggest that the enzyme active site does not have rigid topographic requirements and thus is able to achieve important conformational changes to bind the ligand as long as the pharmacophore pattern in the inhibitor is conserved. Two new potent iodo-containing nonphosphorylatable tyrosine analogues were also incorporated into our lead inhibitory sequence 23, producing the most potent inhibitors for p60c-src PTK identified thus far in our studies. Compounds 29 and 30 exhibit IC50 values of 0.13 and 0.54 microM, respectively. Peptide 29 is 420-fold more potent than the parent peptide 1. Selectivity studies of peptides 23-30 toward p60c-src, Lyn, and Lck PTK showed in general high Lyn/Src and moderate Lck/Src selectivity ratios. We found that the chi1 space constraints of the specialized amino acids, introduced at position 3 of the peptide lead 23, were not as important as the configuration of the Calpha of that residue to recognize the subtle chemical environment surrounding the active site of Src and Lck PTK, as reflected on the obtained Lck/Src selectivity ratios.

Amino Acid Sequence↗
PubMed1998

Nonstructural protein-2 and the replication of canine parvovirus.

The nonstructural protein-2 (NS2) of canine parvovirus (CPV) is produced from the left-hand open reading frame of the viral genome and contains 87 amino-terminal amino acids in common with nonstructural protein 1 (NS1) joined to 78 amino acids from an alternative open reading frame. In the minute virus of mice parvovirus NS2 plays a role in controlling capsid protein assembly and translation in a host-specific manner. The predicted NS2 of CPV is divergent from the proteins of the rodent parvoviruses, and the protein and its functions have not been described. We characterized the large and the small splices of CPV using reverse transcriptase-PCR, NS2 was identified using anti-peptide antibodies against the predicted C-terminal sequence and also by expressing the protein from a plasmid vector. The protein could be detected at low levels in the nucleus and the cytoplasm of a proportion of CPV-infected cells, as well as in cells transfected with the expression plasmid. Virus genomes were prepared with mutations in the splice donor or acceptor sites of the NS2-specific intron or with three different termination codons in the NS2-unique exon. Both splice donor and acceptor mutations resulted in the use of previously cryptic splice sites, and the virus containing the splice donor mutation replicated inefficiently. However, the other four mutant viruses were all viable and replicated efficiently in cat and dog cells, and two mutant viruses that were tested appeared to assemble their capsids in the same manner as did the wildtype. After inoculation of dogs an NS2 mutant virus with a termination codon in the NS2-unique exon replicated to titers similar to those seen for wildtype CPV in several tissues examined.

Alternative Splicing↗
PubMed1998

Modulation of cellular tryptophan metabolism in human fibroblasts by transforming growth factor-beta: selective inhibition of indoleamine 2,3-dioxygenase and tryptophanyl-tRNA synthetase gene expression.

Alterations in the rate of cellular tryptophan metabolism are involved in mediating important biological activities associated with cytokines and growth factors. Indoleamine 2,3-dioxygenase (IDO) and tryptophanyl-tRNA synthetase are enzymes of tryptophan metabolism whose expression in a variety of cells and tissues is highly inducible by interferon-gamma (IFN-gamma). Transforming growth factor-beta (TGF-beta) antagonizes many cellular responses to IFN-gamma. The interaction of these two cytokines plays an important role in maintaining homeostasis during inflammation and repair. In human skin and synovial fibroblasts in vitro, TGF-beta caused time- and dose-dependent abrogation of IFN-gamma-stimulated expression of IDO and tryptophanyl-tRNA synthetase mRNAs. The inhibition was selective and did not appear to be due to down-regulation of IFN-gamma signaling by TGF-beta. In parallel with its effect on IDO mRNA expression, TGF-beta caused a marked reduction in intracellular IDO protein levels and abrogated IDO activity and tryptophan catabolism in these cells induced by IFN-gamma. IFN-gamma caused a rapid and striking increase in the amount of IDO heterogeneous nuclear pre-mRNA and induced transcription of the IDO gene, as demonstrated by transient transfection assays. TGF-beta partially reversed this stimulation. IFN regulatory factor (IRF)-1 and stat1 are cellular intermediates in IFN signaling. Both are implicated in activation of IDO transcription in response to IFN-gamma. The stimulation by IFN-gamma of IRF-1 protein and mRNA expression was not prevented by treatment of fibroblasts with TGF-beta. Furthermore, gel mobility shift assays indicated that TGF-beta did not inhibit the induction of stat1 and IRF-1 binding activity to their cognate DNA recognition sites in the IDO gene promoter. In contrast, the stability of IDO mRNA transcripts was reduced in fibroblasts treated with TGF-beta, as shown by determination of mRNA half-lives following blockade of transcription with 5,6-dichlorobenzimidazole riboside. The findings indicate that TGF-beta prevents the induction of IDO and tryptophanyl-tRNA synthetase gene expression in fibroblasts. The repression of IDO expression by TGF-beta is mediated at both transcriptional and posttranscriptional levels. These results implicate TGF-beta in the negative regulation of tryptophan metabolism, provide evidence for the molecular basis of this regulation, and indicate that cellular tryptophan metabolism is under tight immunological control.

Adult↗