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Biomedical subjects

S Yang

Publications and source records attributed to S Yang.

At least 55 records · Page 3Linked to original sources
PubMed2004

A novel mutation of the DSRAD gene in a Chinese family with dyschromatosis symmetrica hereditaria.

Dyschromatosis symmetrica hereditaria (DSH) is a pigmentary genodermatosis of autosomal dominant inheritance characterized by a mixture of hyperpigmented and hypopigmented macules distributed on the dorsal aspects of the hands and feet. It is caused by mutations of the RNA-specific adenosine deaminase gene. We report the identification of a Chinese family with a three-generation pedigree of DSH, in whom a novel tyrosine substitution mutation in DSRAD was demonstrated: a heterozygous nucleotide A-->G transition at position 2879 in exon 10 of the DSRAD gene was detected.

Adenosine Deaminase↗
PubMed2004

Marie Unna hereditary hypotrichosis: report of a Chinese family and evidence for genetic heterogeneity.

Marie Unna hereditary hypotrichosis (MUHH) is a rare autosomal dominant disorder with progressive hair loss starting in early childhood and aggravating at puberty. Several studies have mapped the MUHH gene to chromosome 8p21. Here we report a Chinese MUHH family with variable phenotypes. All affected individuals have anomalies affecting both hair density and hair shafts. Major clinical characteristics, disease history and histological examination support the diagnosis of MUHH, but the features of scarring in this kindred are modest and none of the patients have vertex hair loss, which is in contrast with typical MUHH. We now report genotyping and linkage analysis using 11 polymorphic microsatellite markers spanning the MUHH locus at 8p. Two-point linkage analysis using these markers revealed significant exclusion of this locus (log of the odds scores < - 2) at Theta = 0 indicating that there is a range of clinical presentations in MUHH, and that more than one genetic locus is responsible for the disorder.

Adult↗
PubMed2004

Hepatic fibrogenesis requires sympathetic neurotransmitters.

BACKGROUND AND AIMS: Hepatic stellate cells (HSC) are activated by liver injury to become proliferative fibrogenic myofibroblasts. This process may be regulated by the sympathetic nervous system (SNS) but the mechanisms involved are unclear. METHODS: We studied cultured HSC and intact mice with liver injury to test the hypothesis that HSC respond to and produce SNS neurotransmitters to promote fibrogenesis. RESULTS: HSC expressed adrenoceptors, catecholamine biosynthetic enzymes, released norepinephrine (NE), and were growth inhibited by alpha- and beta-adrenoceptor antagonists. HSC from dopamine beta-hydroxylase deficient (Dbh(-/-)) mice, which cannot make NE, grew poorly in culture and were rescued by NE. Inhibitor studies demonstrated that this effect was mediated via G protein coupled adrenoceptors, mitogen activated kinases, and phosphatidylinositol 3-kinase. Injury related fibrogenic responses were inhibited in Dbh(-/-) mice, as evidenced by reduced hepatic accumulation of alpha-smooth muscle actin(+ve) HSC and decreased induction of transforming growth factor beta1 (TGF-beta1) and collagen. Treatment with isoprenaline rescued HSC activation. HSC were also reduced in leptin deficient ob/ob mice which have reduced NE levels and are resistant to hepatic fibrosis. Treating ob/ob mice with NE induced HSC proliferation, upregulated hepatic TGF-beta1 and collagen, and increased liver fibrosis. CONCLUSIONS: HSC are hepatic neuroglia that produce and respond to SNS neurotransmitters to promote hepatic fibrosis.

Animals↗
PubMed2004

Expression of iNOS gene in macrophages stimulated with 17beta-estradiol is regulated by free intracellular Ca2+.

17Beta-estradiol has potent Ca2+ ionophore capability and its signaling in macrophages is mediated through binding to surface and genomic receptors, resulting in transient nitric oxide (NO) elaboration. We decided to examine if the transient release of NO is due to Ca2+ influx pattern or the quenching effect of superoxide (*O2-) through peroxynitrite formation. Differential chelation of intracellular Ca2+ ([Ca2+]i) showed that NO generation was favored by [Ca2+]i concentration of 237 nM. Application of an estrogen receptor antagonist ICI 182 780 resulted in attenuation of estradiol mediated NO release. Studies directed at identifying the possible role of *O2-; in the attenuation of NO showed no supportive evidence. Inhibition of extracellular Ca2+ channel or extracellular and intracellular Ca2+ channels showed data consistent with a case for optimum Ca2+ influx signal favoring iNOS gene expression, accompanied by an elevation in iNOS protein. These data show that Ca2+ influx pattern determines macrophage NO elaboration.

Animals↗
PubMed2004

Ghrelin is expressed in a novel endocrine cell type in developing rat islets and inhibits insulin secretion from INS-1 (832/13) cells.

Ghrelin is produced mainly by endocrine cells in the stomach and is an endogenous ligand for the growth hormone secretagogue receptor (GHS-R). It also influences feeding behavior, metabolic regulation, and energy balance. It affects islet hormone secretion, and expression of ghrelin and GHS-R in the pancreas has been reported. In human islets, ghrelin expression is highest pre- and neonatally. We examined ghrelin and GHS-R in rat islets during development with immunocytochemistry and in situ hybridization. We also studied the effect of ghrelin on insulin secretion from INS-1 (832/13) cells and the expression of GHS-R in these cells. We found ghrelin expression in rat islet endocrine cells from mid-gestation to 1 month postnatally. Islet expression of GHS-R mRNA was detected from late fetal stages to adult. The onset of islet ghrelin expression preceded that of gastric ghrelin. Islet ghrelin cells constitute a separate and novel islet cell population throughout development. However, during a short perinatal period a minor subpopulation of the ghrelin cells co-expressed glucagon or pancreatic polypeptide. Markers for cell lineage, proliferation, and duct cells revealed that the ghrelin cells proliferate, originate from duct cells, and share lineage with glucagon cells. Ghrelin dose-dependently inhibited glucose-stimulated insulin secretion from INS-1 (832/13) cells, and GHS-R was detected in the cells. We conclude that ghrelin is expressed in a novel developmentally regulated endocrine islet cell type in the rat pancreas and that ghrelin inhibits glucose-stimulated insulin secretion via a direct effect on the beta-cell.

Animals↗
PubMed2004

IL-1alpha stimulates cathepsin K expression in osteoclasts via the tyrosine kinase-NF-kappaB pathway.

Interleukin-1alpha (IL-1alpha) is a powerful activator of osteoclast cells. However, the underlying mechanism for this activation is unknown. In this study, we reveal that IL-1alpha up-regulates the expression of cathepsin K protein, a key protease in bone resorption, by five-fold. Northern blot analysis and promoter analysis show that this induction occurs at the transcriptional level, in a dose-responsive and time-dependent manner. No increase in expression occurs in the presence of either pyrrolidine dithiocarbamate (PDTC), a selective inhibitor of NF-kappaB, or Genistein, a protein tyrosine kinase inhibitor, suggesting that IL-1alpha up-regulation may be via the tyrosine kinase-NF-kappaB pathway to regulate cathepsin K expression. Antisense oligonucleotides to p65, but not the p50 subunit of NF-kappaB, suppress the IL-1alpha-induced expression of cathepsin K. We therefore conclude that IL-1alpha up-regulates cathepsin K gene expression at the transcription level, and this regulation may be via the tyrosine-kinase-NF-kappaB pathway.

Animals↗
PubMed2004

What is the structure of the RecA-DNA filament?

The bacterial RecA protein has been a model system for understanding how a protein can catalyze homologous genetic recombination. RecA-like proteins have now been characterized from many organisms, from bacteriophage to humans. Some of the RecA-like proteins, including human RAD51, appear to function as helical filaments formed on DNA. However, we currently have high resolution structures of inactive forms of the protein, and low resolution structures of the active complexes formed by RecA-like proteins on DNA in the presence of ATP or ATP analogs. Within a crystal of the E. coli RecA protein, a helical polymer exists, and it has been widely assumed that this polymer is quite similar to the active helical filament formed on DNA. Recent developments have suggested that this may not be the case.

Adenosine Triphosphatases↗
PubMed2004

Cell therapy for ischemic heart disease.

Despite advances in pharmacological therapies, cardiovascular surgery, use of mechanical assist devices, and organ transplantation, more than 50% of the patients with clinically evident heart failure die within 5 years of the initial diagnosis. The use of cellular therapy offers a promising approach for both the prevention and treatment of heart failure. This review will discuss the current state of this emerging field and the prospects to introduce the method into clinical practice. Since functional restoration of the damaged heart presents a formidable challenge, developing strategies for the prevention of postinfarct heart failure remains of utmost priority. Recent research has provided evidence that several cell lines including adult or embryonic stem cells, skeletal myoblasts, fetal cardiomyocytes or fibroblasts may be useful in strategies that aim to both prevent and treat heart failure through establishment of new blood vessels supplying surviving heart muscle cells and replacement of damaged heart muscle cells themselves. It is therefore reasonable to anticipate that new strategies will be developed to optimize cell delivery, homing and survival in the failing myocardium improving myocardial recovery after acute or chronic deterioration.

Animals↗
PubMed2003

Measurements of GnE/GnM from the 2H(e-->,en-->)1H Reaction to Q2=1.45 (GeV/c)2.

We report new measurements of the ratio of the electric form factor to the magnetic form factor of the neutron, G(n)(E)/G(n)(M), obtained via recoil polarimetry from the quasielastic 2H(e-->,e(')n-->)1H reaction at Q2 values of 0.45, 1.13, and 1.45 (GeV/c)(2) with relative statistical uncertainties of 7.6% and 8.4% at the two higher Q2 points, which points have never been achieved in polarization measurements.

Journal Article↗
PubMed2003

Tracheobronchial amyloidosis treated with rigid bronchoscopy and stenting.

Tracheobronchial amyloidosis (TBA) is an uncommon disease that can cause airway obstruction. We present a case of TBA in a 20-year-old man that was treated successfully with rigid bronchoscopy and stenting. The patient presented with progressive dyspnea despite having had a tracheostomy fashioned at another institution. Airway obstruction secondary to TBA was found distal to the tracheostomy. The amyloid protein subtype was AA, which is uncommon and is seldom of clinical significance in the respiratory tract. The patient underwent rigid bronchoscopy to remove the amyloid protein causing the airway obstruction. A Dumon silicone stent was then inserted to alleviate the obstruction. Thereafter, he recovered well and was discharged without a tracheostomy. This report shows that in patients with TBA causing airway obstruction, excellent results can be obtained with rigid bronchoscopy and stenting of the obstructing lesion.

Adult↗
PubMed2003

Evidence for disaggregation of oligomeric G(o)alpha induced by guanosine-5;-3-O-(thio)triphosphate activation.

Myristoylated G(o)alpha was expressed in and highly purified from Escherichia coli strain JM109 cotransformed with pQE60 (G(o)alpha) and pBB131 (N-myristoyltransferase, NMT). Non-denaturing gel electrophoresis and gel filtration analysis revealed that the G(o)alpha, in its GDP-bound form, could form oligomers involving dimer, trimer, tetramer, pentamer, or hexamer and guanosine 5;-3-O-(thio)triphosphate (GTPgammaS) activation induced disaggregation of the G(o)alpha oligomers to monomers. The G(o)alpha was crosslinked by a cross-linker, N,N-1,4-phenylenedimaleimide (p-PDM), yielding multiple crosslinked products. In contrast, no obvious cross-linking occurred when G(o)alpha was pretreated with GTPgammaS. Immunoblot analysis also demonstrated oligomerization of the purified G(o)alpha proteins and its disaggregation triggered by GTPgammaS. These results provided direct evidence for the "disaggregation-coupling" theory and the disaggregation action of GTPgammaS may further elucidate the regulatory role of GDP/GTP exchange in G protein-coupled signal transduction pathways.

Blotting, Western↗
PubMed2003

Identification of a locus for porokeratosis palmaris et plantaris disseminata to a 6.9-cM region at chromosome 12q24.1-24.2.

BACKGROUND: Porokeratosis palmaris et plantaris disseminata (PPPD) is a rare autosomal dominant dyskeratotic disorder characterized by a cornoid lamella with parakeratosis, hyperkeratosis and loss of granular layers. The genetic basis of this disease is still unknown. Two loci for disseminated superficial actinic porokeratosis (DSAP) were found to be located on 12q23.2-24.1 and 15q25.1-26.1. Both PPPD and DSAP are disseminated types of porokeratosis. OBJECTIVES: To locate the locus for PPPD, thereby facilitating the identification of this disease gene and leading to an understanding of the pathogenesis of porokeratosis. METHODS: Genotyping was performed in a Chinese family with PPPD using polymorphic microsatellite markers on 12q and 15q. RESULTS: The locus for PPPD is located within a 6.9-cM region between markers D12S1613 and D12S1341, with a maximum two-point LOD score of 8.14 (theta = 0.00) at D12S1335. CONCLUSIONS: This study provides a map location for isolation of a gene causing PPPD.

Adolescent↗
PubMed2003

A new glycine substitution mutation in the COL7A1 gene in a Chinese family with dominant dystrophic epidermolysis bullosa.

Dystrophic epidermolysis bullosa (DEB) is caused by mutations in the COL7A1 gene encoding type VII collagen, the major component of anchoring fibrils. The characteristic genetic lesion in dominant DEB (DDEB) is a glycine substitution in the collagenous domain of the protein. In this study, we identified a Chinese family with a four-generation pedigree of DDEB, in whom a novel glycine substitution mutation in COL7A1 was demonstrated. A heterozygous nucleotide G-->A transition at position 6208 in exon 74 of COL7A1 was detected, which resulted in a glycine to arginine substitution (G2070R) in the triple-helical domain of type VII collagen. This substitution was not found in 110 unrelated normal alleles. This report emphasizes the predominance of glycine substitution mutations in DDEB and contributes to the expanding database on COL7A1 mutations.

Adolescent↗
PubMed2003

Induction of cyclooxygenase-2 in human endometrial stromal cells by malignant endometrial epithelial cells: evidence for the involvement of extracellularly regulated kinases and CCAAT/enhancer binding proteins.

We previously reported that human malignant endometrial epithelial cell conditioned medium (MECM) up-regulated cyclooxygenase (COX)-2 mRNA and protein levels in human normal endometrial stromal cells (ESC). Here we showed that pretreatment with a selective inhibitor of the extracellularly regulated kinase (ERK)1/2 signaling pathway blocked the MECM-induced COX-2 expression in ESC. Transient transfection assays indicated critical roles of a cAMP response element (CRE,-59/-53 bp) and a nuclear factor for interleukin (IL)-6 expression (NF-IL6) site (-132/-124 bp) in the regulation of basal and MECM-induced activity of COX-2 gene promoter in ESC. Employing electrophoretic mobility shift assays, we demonstrated that increased functional binding of CCAAT/enhancer binding protein (C/EBP)alpha, C/EBPbeta and upstream stimulatory factor-2 to the CRE and C/EBPalpha and C/EBPbeta to the NF-IL6 site were, at least in part, responsible for MECM-induced COX-2 expression in ESC. Moreover, overexpression of C/EBPalpha and C/EBPbeta significantly induced COX-2 promoter activity in ESC. Collectively, these results suggest that the basal and MECM-induced transcription of the COX-2 gene in ESC is regulated through a combination of the CRE and the NF-IL6 site by functional interactions of C/EBPalpha and C/EBPbeta.

Base Sequence↗
PubMed2003

Both stress experience and age determine the impairment or enhancement effect of stress on spatial memory retrieval.

It has been documented that stress or glucocorticoids have conflicting effects on memory under different conditions. However, it is not fully understood why stress can either impair or enhance memory. Here, we have examined the performance of six age groups of Wistar rats in a water maze spatial task to evaluate the effects of stress under different conditions. We found that the impairment or enhancement effect of an 'elevated platform' (EP) stress on memory was dependent on previous stress experience and on age. EP stress impaired memory retrieval in water maze naive animals, but enhanced rather than impaired memory retrieval in young water maze stress-experienced animals. Furthermore, exogenously applied corticosterone or foot shock stress before water maze training prevented the impairment of memory retrieval that should be induced by treatment with corticosterone or foot shock before the 'probe trial'. Again, memory retrieval was enhanced in young animals under these conditions, and this enhancement can be prevented by the glucocorticoid receptor antagonist RU 38486. Thus, glucocorticoid receptor activation not only induced impairment of memory but also increased the capacity of young animals to overcome a later stress. The present findings suggest that the effect of stress on memory can be switched from impairment to enhancement dependent on both stress experience and age.

Aging↗
PubMed2003

Delta opioid peptides derived from plant proteins.

Opioid peptides showing selectivity for delta receptor have been isolated from enzymatic digests of plant proteins. Five peptides were derived from wheat gluten, and named gluten exorphins A5, A4, B5, B4 and C. Two opioid peptides were also released from spinach ribulose-bisphosphate-carboxylase/oxygenase (Rubisco), and named rubiscolins-5 and -6. Among them, gluten exorphin 5A (Gly-Tyr-Tyr-Pro-Thr) and rubiscolin 6 (Tyr-Pro-Leu-Asp-Leu-Phe) improved learning performance in step-through type passive avoidance test after post-training oral administration in mice at doses of 300 mg/kg and 100 mg/kg, respectively, which are smaller than those required for antinociceptive activity.

Analgesics, Opioid↗
PubMed2002

IL-1Ra and vIL-10 gene transfer using retroviral vectors ameliorates particle-associated inflammation in the murine air pouch model.

OBJECTIVE: This study examined anti- inflammatory gene therapy to ameliorate tissue responses to ultra high molecular weight polyethylene (UHMWPE) particles in the murine air pouch. METHODS: Retroviruses encoding human interleukin- 1 receptor antagonist (IL-1Ra), viral interleukin-10 (vIL-10), or LacZ (reporter) genes were injected into murine air pouches stimulated by UHMWPE particles. Pouch membranes and fluids were harvested at 1, 3 and 7 days post gene-transduction, and assayed for markers of inflammation using histological, molecular, and immunological techniques. RESULTS: Real time RT-PCR and ELISA showed a strong production of IL-1beta in pouch tissue and lavage fluid induced by particle stimulation, accompanied by a lower expression of IL-6, TNF-alpha and IL-4. Transduction of IL-1Ra or vIL-10 genes resulted in a significant reduction of IL-1beta both at the mRNA and at the protein level. The gene therapy also resulted in diminution of IL-6 and TNF-alpha expression. In addition, significant elevation of TGF-beta expression was observed in IL-1Ra transduced pouches. Histological analysis revealed that the membranes of pouches transduced with vIL-10 or IL-1Ra were significantly less inflamed than the membranes of non-viral and LacZ-transduced pouches, with less cellular proliferation and lowered monocyte/macrophage influx. CONCLUSIONS: IL-1Ra or vIL-10 gene transduction was effective in ameliorating local inflammation by reducing the IL-1 production and subsequent cellular events elicited in response to UHMWPE particles in this model. These findings suggest that IL-1 directed gene therapy might be excellent therapeutic candidates to prevent or retard the inflammatory response to wear debris that contributes to the pathology of aseptic loosening.

Air↗