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S Yu

Publications and source records attributed to S Yu.

At least 127 records · Page 7Linked to original sources
PubMed2000

Polymorphisms in the CAG repeat--a source of error in Huntington disease DNA testing.

Five of 400 patients (1.3%), referred for Huntington disease DNA testing, demonstrated a single allele on CAG alone, but two alleles when the CAG + CCG repeats were measured. The PCR assay failed to detect one allele in the CAG alone assay because of single-base silent polymorphisms in the penultimate or the last CAG repeat. The region around and within the CAG repeat sequence in the Huntington disease gene is a hot-spot for DNA polymorphisms, which can occur in up to 1% of subjects tested for Huntington disease. These polymorphisms may interfere with amplification by PCR, and so have the potential to produce a diagnostic error.

Adult↗
PubMed2000

Protection of Rpe65-deficient mice identifies rhodopsin as a mediator of light-induced retinal degeneration.

Light-induced apoptosis of photoreceptors represents an animal model for retinal degeneration. Major human diseases that affect vision, such as age-related macular degeneration (AMD) and some forms of retinitis pigmentosa (RP), may be promoted by light. The receptor mediating light damage, however, has not yet been conclusively identified; candidate molecules include prostaglandin synthase, cytochrome oxidase, rhodopsin, and opsins of the cones and the retinal pigment epithelium (PE). We exposed to bright light two groups of genetically altered mice that lack the visual pigment rhodopsin (Rpe65-/- and Rho-/-). The gene Rpe65 is specifically expressed in the PE and essential for the re-isomerization of all-trans retinol in the visual cycle and thus for the regeneration of rhodopsin after bleaching. Rho-/- mice do not express the apoprotein opsin in photoreceptors, which, consequently, do not contain rhodopsin. We show that photoreceptors lacking rhodopsin in these mice are completely protected against light-induced apoptosis. The transcription factor AP-1, a central element in the apoptotic response to light, is not activated in the absence of rhodopsin, indicating that rhodopsin is essential for the generation or transduction of the intracellular death signal induced by light.

Animals↗
PubMed2000

Accumulation of cystathionine, cystathionine ketimine, and perhydro-1,4-thiazepine-3,5-dicarboxylic acid in whole brain and various regions of the brain of D, L-propargylglycine-treated rats.

Experimental cystathioninuria was induced in rats by administration of the cystathionine gamma-lyase inhibitor, D,L-propargylglycine. The cystathionine metabolites, cystathionine ketimine (CK) and perhydro-1,4-thiazepine-3,5-dicarboxylic acid (PHTZDC), were identified in whole brain and various regions of the brain in D,L-propargylglycine-treated rats. The concentration of CK and PHTZDC in whole brain and various regions of the brain increased gradually after administration of D,L-propargylglycine, and reached the highest value at about 20 hours. CK and PHTZDC accumulated in whole brain and various regions of the brain in proportion to the amount of accumulated cystathionine after D,L-propargylglycine administration. The concentration of these compounds in the cerebellum was higher versus the other regions of the rat brain.

Alkynes↗
PubMed2000

Intrathymic alloantigen-mediated, tolerant, completely major histocompatibility complex-mismatched mouse hearts are specifically rejected by adoptively transferred anti-class I L(d+)-specific 2C cells.

BACKGROUND: Tolerance to cardiac allografts can be induced in mice and rats by the injection of donor alloantigen into the thymus in combination with a CD4 T-cell-depleting antibody. CD8(+) cells in these animals are hyporesponsive to graft-specific alloantigens. Most of the CD8(+) T cells in the transgenic 2C mouse express a T-cell receptor specific for the class I major histocompatibility complex L(d+) locus. This study was designed to determine whether the adoptive transfer of these 2C T cells could precipitate rejection of a tolerant, completely major histocompatibility complex-mismatched L(d+) or L(d-) heart. METHODS: C57BL/6 mice (L(d-)) were given 10 x 10(6) cells of BALB/c (L(d+)) or dm2 (BALB/c background lacking L(d) [L(d-)]) splenocytes intrathymically and GK1. 5 (10 mg/kg) intraperitoneally. Twenty-one days later, BALB/c or dm2 hearts were transplanted. On the day of transplantation or after long-term allograft acceptance, recipients received naive 2C cells or 2C cells sensitized by in vitro mixed lymphocyte culture with BALB/c (L(d+)). RESULTS: Mean survival time of BALB/c cardiac allografts in untreated C57BL/6 mice was 7.3 days, although 73% of the mice that were pretreated with BALB/c splenocytes IT plus GK1.5 accepted the donor antigen-specific heart allografts indefinitely. All recipients that were pretreated with the intrathymic plus GK1.5 and that were injected with naive 2C cells at the time of heart transplantation experienced rejection of the BALB/c (L(d+)), but not the dm2 (L(d-)) hearts. In contrast, naive 2C cells could not reject tolerant (>30 days acceptance) BALB/c (L(d+)) hearts. 2C cells sensitized in vitro against L(d) were able to reject established BALB/c hearts but could not reject the L(d-) dm2 hearts. CONCLUSIONS: L(d)-specific 2C T-cell receptor transgenic T cells that are adoptively transferred to recipients will precipitate the rejection of accepted hearts that express class I L(d+) in mice rendered tolerant by an intrathymic injection of alloantigen plus anti-CD4 monoclonal antibodies.

Adoptive Transfer↗
PubMed2000

Invasive and noninvasive haemodynamic monitoring of acutely ill sepsis and septic shock patients in the emergency department.

The objective of this study was to describe early circulatory events of patients presenting to the emergency department (ED) with severe sepsis or septic shock. Invasive and noninvasive monitoring were used to evaluate sequential patterns of both central haemodynamics and peripheral tissue perfusion/oxygenation and to test the hypothesis that increased cardiac output is an early compensation to increased body metabolism. This is a prospective observational study of 45 patients who entered the ED with severe sepsis or septic shock in an urban academic ED. Invasive clinical monitoring was performed using a radial artery catheter and a thermodilution pulmonary artery catheter. Noninvasive monitoring consisted of an improved thoracic electrical bioimpedance device to estimate cardiac output; pulse oximetry for arterial saturation to reflect changes in pulmonary function, and transcutaneous oxygen (PtcO2) and carbon dioxide tensions (PtcCO2) as a reflection of tissue perfusion. Survivors had higher cardiac index, mean arterial pressure (MAP), and better tissue perfusion as measured by PtcO2, oxygen delivery, and oxygen consumption. Oxygen extraction ratio was higher in the nonsurvivors (p < 0.05) and there were episodes of high PtcCO2 values in the nonsurvivors. No significant differences were found in the heart rate, PAOP (wedge pressure) and SaO2 by pulse oximetry between the two groups. It is concluded that ED monitoring septic patients provides a unique opportunity to document early physiologic interactions between cardiac, pulmonary, and tissue perfusion functions in surviving and nonsurviving patients with septic shock. The data is consistent with the concept that increased cardiac output is an early compensatory response to increased body metabolism. Real time haemodynamic monitoring of patients in the ED provides early warning of outcome and may be used to guide therapy.

Cardiac Output↗
PubMed2000

A CAD system for the automatic detection of clustered microcalcifications in digitized mammogram films.

Clusters of microcalcifications in mammograms are an important early sign of breast cancer. This paper presents a computer-aided diagnosis (CAD) system for the automatic detection of clustered microcalcifications in digitized mammograms. The proposed system consists of two main steps. First, potential microcalcification pixels in the mammograms are segmented out by using mixed features consisting of wavelet features and gray level statistical features, and labeled into potential individual microcalcification objects by their spatial connectivity. Second, individual microcalcifications are detected by using a set of 31 features extracted from the potential individual microcalcification objects. The discriminatory power of these features is analyzed using general regression neural networks via sequential forward and sequential backward selection methods. The classifiers used in these two steps are both multilayer feedforward neural networks. The method is applied to a database of 40 mammograms (Nijmegen database) containing 105 clusters of microcalcifications. A free-response operating characteristics (FROC) curve is used to evaluate the performance. Results show that the proposed system gives quite satisfactory detection performance. In particular, a 90% mean true positive detection rate is achieved at the cost of 0.5 false positive per image when mixed features are used in the first step and 15 features selected by the sequential backward selection method are used in the second step. However, we must be cautious when interpreting the results, since the 20 training samples are also used in the testing step.

Breast Neoplasms↗
PubMed2000

Lysophospholipid growth factors in the initiation, progression, metastases, and management of ovarian cancer.

Levels of lysophosphatidic acid (LPA) and lysophosphatidylcholine (LPC) are elevated in the plasma and ascites of ovarian cancer patients, but not in most other tumor types. LPA increases cell proliferation, cell survival, resistance to cisplatin, cell shrinkage, and production of vascular endothelial growth factor, urokinase plasminogen activator, and LPA itself in ovarian cancer cells, but not in normal ovarian surface epithelial cells. PSP24 and members of the endothelial differentiation gene (EDG) family (EDG1, EDG2, EDG4, and EDG7) of G protein-coupled receptors mediate LPA signaling. Ovarian cancer cell lines do not express EDG1 mRNA, have variable EDG2 mRNA and protein levels, and frequently exhibit levels of EDG4 mRNA and protein, suggesting that EDG4 may contribute to the deleterious effects of LPA in ovarian cancer. In contrast, activation of the EDG2 LPA receptor on ovarian cancer cells may lead to apoptosis and counter the effects of other LPA receptors. Thus, the development of agonists and antagonists for the appropriate spectrum of LPA receptors may alter proliferation, apoptosis, or response to therapy of ovarian cancer cells. Indeed, over 60% of all current drugs target the G protein-coupled family of receptors, making the LPA receptor family a "drugable" target. LPC, although not as thoroughly studied, increases cellular proliferation and mediates multiple other functions through unique signaling pathways.

Ascites↗
PubMed2000

Identification of a methylation imprint mark within the mouse Gnas locus.

The imprinted mouse gene Gnas produces the G protein alpha-subunit G(S)alpha and several other gene products by using alternative promoters and first exons. G(S)alpha is maternally expressed in some tissues and biallelically expressed in most other tissues, while the gene products NESP55 and XLalphas are maternally and paternally expressed, respectively. We investigated the mechanisms of Gnas imprinting. The G(S)alpha promoter and first exon are not methylated on either allele. A further upstream region (approximately from positions -3400 to -939 relative to the G(S)alpha translational start site) is methylated only on the maternal allele in all adult somatic tissues and in early postimplantation development. Within this region lies a fourth promoter and first exon (exon 1A) that generates paternal-specific mRNAs of unknown function. Exon 1A and G(S)alpha mRNAs have similar expression patterns, making competition between their promoters unlikely. Differential methylation in this region is established during gametogenesis, being present in oocytes and absent in spermatozoa, and is maintained in preimplantation E3. 5d blastocysts. Therefore, this region is a methylation imprint mark. In contrast, differential methylation of the NESP55 and XLalphas promoter regions (Nesp and Gnasxl) is not established during gametogenesis. The methylation imprint mark that we identified may be important for the tissue-specific imprinting of G(S)alpha.

Animals↗
PubMed2000

MyoD-dependent induction during myoblast differentiation of p204, a protein also inducible by interferon.

p204, an interferon-inducible p200 family protein, inhibits rRNA synthesis in fibroblasts by blocking the binding of the upstream binding factor transcription factor to DNA. Here we report that among 10 adult mouse tissues tested, the level of p204 was highest in heart and skeletal muscles. In cultured C2C12 skeletal muscle myoblasts, p204 was nucleoplasmic and its level was low. During myoblast fusion this level strongly increased, p204 became phosphorylated, and the bulk of p204 appeared in the cytoplasm of the myotubes. Leptomycin B, an inhibitor of nuclear export that blocked myoblast fusion, inhibited the nuclear export signal-dependent translocation of p204 to the cytoplasm. The increase in the p204 level during myoblast fusion was a consequence of MyoD transcription factor binding to several MyoD-specific sequences in the gene encoding p204, followed by transcription. Overexpression of p204 (in C2C12 myoblasts carrying an inducible p204 expression plasmid) accelerated the fusion of myoblasts to myotubes in differentiation medium and induced the fusion even in growth medium. The level of p204 in mouse heart muscle strongly increased during differentiation; it was barely detectable in 10. 5-day-old embryos, reached the peak level in 16.5-day-old embryos, and remained high thereafter. p204 is the second p200 family protein (after p202a) found to be involved in muscle differentiation. (p202a was formerly designated p202. The new designation is due to the identification of a highly similar protein-p202b [H. Wang, G. Chatterjee, J. J. Meyer, C. J. Liu, N. A. Manjunath, P. Bray-Ward, and P. Lengyel, Genomics 60:281-294, 1999].) These results reveal that p204 and p202a function in both muscle differentiation and interferon action.

Actinin↗
PubMed2000

Variable imprinting of the heterotrimeric G protein G(s) alpha-subunit within different segments of the nephron.

The heterotrimeric G protein G(s) is required for hormone-stimulated intracellular cAMP generation because it couples hormone receptors to the enzyme adenylyl cyclase. Hormones that activate G(s) in the kidney include parathyroid hormone, glucagon, calcitonin, and vasopressin. Recently, it has been demonstrated that the G(s)alpha gene is imprinted in a tissue-specific manner, leading to preferential expression of G(s)alpha from the maternal allele in some tissues. In the kidney, G(s)alpha is imprinted in the proximal tubule but not in more distal nephron segments, such as the thick ascending limb or collecting duct. This most likely explains why in both humans and mice heterozygous mutations in the maternal allele lead to parathyroid hormone resistance in the proximal tubule whereas mutations in the paternal allele do not. In contrast, heterozygous mutations have little effect on vasopressin action in the collecting ducts. In mice with heterozygous null G(s)alpha mutations (both those with mutations on the maternal or paternal allele), expression of the Na-K-2Cl cotransporter was decreased in the thick ascending limb, suggesting that its expression is regulated by cAMP. The G(s)alpha genes also generate alternative, oppositely imprinted transcripts encoding XLalphas, a G(s)alpha isoform with a long NH(2)-terminal extension, and NESP55, a chromogranin-like neurosecretory protein. The role, if any, of these proteins in renal physiology is unknown.

Animals↗
PubMed2000

A GNAS1 imprinting defect in pseudohypoparathyroidism type IB.

Pseudohypoparathyroidism type IB (PHPIB) is characterized by renal resistance to parathyroid hormone (PTH) and the absence of other endocrine or physical abnormalities. Familial PHPIB has been mapped to 20q13, near GNAS1, which encodes G(s)alpha, the G protein alpha-subunit required for receptor-stimulated cAMP generation. However, G(s)alpha function is normal in blood cells from PHPIB patients, ruling out mutations within the G(s)alpha coding region. In mice G(s)alpha is expressed only from the maternal allele in renal proximal tubules (the site of PTH action) but is biallelically expressed in most other tissues. Studies in patients with Albright hereditary osteodystrophy suggest a similar G(s)alpha imprinting pattern in humans. Here we identify a region upstream of the G(s)alpha promoter that is normally methylated on the maternal allele and unmethylated on the paternal allele, but that is unmethylated on both alleles in all 13 PHPIB patients studied. Within this region is an alternative promoter and first exon (exon 1A), generating transcripts that are normally expressed only from the paternal allele, but that are biallelically expressed in PHPIB patients. Therefore, PHPIB is associated with a paternal-specific imprinting pattern of the exon 1A region on both alleles, which may lead to decreased G(s)alpha expression in renal proximal tubules. We propose that loss of exon 1A imprinting is the cause of PHPIB.

Alleles↗
PubMed2000

Paternal versus maternal transmission of a stimulatory G-protein alpha subunit knockout produces opposite effects on energy metabolism.

Heterozygous disruption of Gnas, the gene encoding the stimulatory G-protein alpha subunit (G(s)alpha), leads to distinct phenotypes depending on whether the maternal (m-/+) or paternal (+/p-) allele is disrupted. G(s)alpha is imprinted, with the maternal allele preferentially expressed in adipose tissue. Hence, expression is decreased in m-/+ mice but normal in +/p- mice. M-/+ mice become obese, with increased lipid per cell in white and brown adipose tissue, whereas +/p- mice are thin, with decreased lipid in adipose tissue. These effects are not due to abnormalities in thyroid hormone status, food intake, or leptin secretion. +/p- mice are hypermetabolic at both ambient temperature (21 degrees C) and thermoneutrality (30 degrees C). In contrast, m-/+ mice are hypometabolic at ambient temperature and eumetabolic at thermoneutrality M-/+ and wild-type mice have similar dose-response curves for metabolic response to a beta(3)-adrenergic agonist, CL316243, indicating normal sensitivity of adipose tissue to sympathetic stimulation. Measurement of urinary catecholamines suggests that +/p- and m-/+ mice have increased and decreased activation of the sympathetic nervous system, respectively. This is to our knowledge the first animal model in which a single genetic defect leads to opposite effects on energy metabolism depending on parental inheritance. This probably results from deficiency of maternal- and paternal-specific Gnas gene products, respectively.

Adrenergic beta-Agonists↗
PubMed2000

[DNA polymorphism of Pvu II site in the lipoprotein lipase gene in patients with type 2 diabetes mellitus].

OBJECTIVE: To study the relationship between the lipoprotein lipase(LPL) gene and type 2 diabetes mellitus (DM) and its lipid metabolism. METHODS: PCR-RFLP method was used to determine the DNA polymorphism of 6th intron at LPL gene in 127 DM patients and 125 controls. RESULTS: The allele frequencies in case and control groups were 69.3%, 63.6% for "P+" and 30.7%, 36.4% for "P-", respectively; the frequencies of genotypes were 48.0%, 44.8% for P+/P+, 42.5%, 37. 6% for P+/P- and 9.45%, 17.6% for P-/P-, respectively. There was no significant difference in frequencies of genotypes or alleles between the two groups. The LPL Pvu II polymorphism in Chinese population was similar to that in Japanese population, and was different from that in European and American population. CONCLUSION: The LPL-Pvu II-RFLP in Chinese population is not significantly associated with type 2 diabetes mellitus. The significant difference of Pvu II-RFLP among various races was observed.

Adult↗
PubMed2000

Oesophageal cancer and occupational exposure to rubber: a nested case-control study.

Findings for cancer of the oesophagus in the rubber industry are not consistent between studies, and derive from too few studies. Few studies were carried out to examine risks of oesophageal cancer in different departments and the confounding by non-occupational risk factors such as smoking, drinking, and economic status. In this paper these questions have been explored. Following a nested case-control study, the data were used of nine oesophageal cancer deaths during 1973-1995 and 36 controls matched for sex and age from the same cohort of a rubber plant workers. Oesophageal cancer risks for exposure to rubber were assessed, unadjusted and adjusted for non-occupational factors by conditional logistic regression. In grouped analysis, odds ratios (ORs) for oesophageal cancer were found to be 2.67 (95%CI=0.42,17.0) for milling, etc. workers and 1. 40 (95%CI=0.24,7.97) for building workers, who worked for one or more years. No excess risks were found in the remaining three departments. The models for continuous exposure variables indicated that a one-unit year change in the milling, etc. department was associated with a 4% increment in the OR. When adjusted for serum cholesterol level, the 6% increase (OR) was observed. Significant associations between risk for oesophageal cancer and specific exposures or processes within the rubber plant were not found. The slight excess risk for oesophageal cancer in the rubber plant may be related to exposure to dusts and solvents.

Adult↗
PubMed2000

Pharmacophore/receptor models for GABA(A)/BzR alpha2beta3gamma2, alpha3beta3gamma2 and alpha4beta3gamma2 recombinant subtypes. Included volume analysis and comparison to alpha1beta3gamma2, alpha5beta3gamma2, and alpha6beta3gamma2 subtypes.

Pharmacophore/receptor models for 6 recombinant GABA(A)/BzR subtypes (alphax beta3gamma2, x = 1-6) have been established via an SAR ligand mapping approach. This study was based on the affinities of 166 BzR ligands at 6 distinct (alpha1-6beta3gamma2) recombinant GABA(A)/BzR receptor subtypes from at least twelve different structural families. Examination of the included volumes indicated that the shapes of binding pockets for alpha1, alpha2 and alpha3 subtypes are very similar to each other. Region L2 for the alpha5 containing subtype appeared to be larger in size than the analogous region of the other receptor subtypes. Region L(Di), in contrast, appeared to be larger in the alpha1 subtype than in the other subtypes. Moreover, region L3 in the alpha6 subtype is either very small or nonexistent in this diazepam insensitive "DI" subtype as compared to the other subtypes. Preliminary results for the alpha4-containing receptor subtype (DI) indicate that L3 in the alpha4 subtype suffers a similar fate. Use of the pharmacophore/receptor models for these subtypes have resulted in the design of novel BzR ligands selective for the alpha5beta3gamma2, receptor subtype.

Animals↗
PubMed2000

Evaluation of technetium-99m ciprofloxacin (Infecton) in the imaging of infection.

INTRODUCTION: The aim of this study was to evaluate the usefulness of technetium-99m (Tc-99m) ciprofloxacin in imaging inflammation/infection. The ciprofloxacin for labelling, as a kit, was obtained from St Bartholomew's Hospital in London. MATERIALS AND METHODS: Patients were injected intravenously with Tc-99m ciprofloxacin and imaging was done at 10 minutes, 4 hours and 24 hours if necessary. Tomographic images (SPECT) were obtained in a few patients. Ninety-six patients were studied using Tc-99m ciprofloxacin. Forty-eight patients had bone scans and 22 had Tc-99m IgG scans. Eight patients were imaged using Tc-99m HMPAO labelled white blood cell, and bacteriological culture results were available in 24 patients. Organisms cultured included Acinetobacter baumanii, Streptococcus, Staphylococcus aureus, Pseudomonas, Klebsiella, Blastococidia, Methicillin-resistant S. aureus, Salmonella and Candida. RESULTS: Findings were evaluated against microbiology, alternative imaging modalities and clinical outcome. There were 47 true positives, 33 true negatives, 5 false positives and 11 false negatives, giving a sensitivity of 81% and specificity of 87%. The positive and negative predictive values were 90% and 75%, respectively. There were no side effects and the scan was particularly useful in the evaluation of painful joint prosthesis to exclude infection. Repeat studies on 8 patients given antibiotics over a long period were very useful in deciding on termination of the antibiotic treatment.

Abscess↗