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Biomedical subjects

S Yu

Publications and source records attributed to S Yu.

At least 37 records · Page 2Linked to original sources
PubMed2005

Large-scale synthesis of "Cpep" RNA monomers and their application in automated RNA synthesis.

Small interfering RNAs (siRNA) are the latest candidates for oligonucleotide-based therapeutics. Should siRNA be successful in clinical trials, a huge demand for synthetic RNA is anticipated. We believe that 1-(4-chlorophenyl)-4-ethoxypiperidin-4-yl (Cpep) is an ideal 2'-protecting group for large-scale syntheses. Unlike 2'-silyl groups, mild acid hydrolysis instead of fluoride ion is used for the 2'-deprotection. The syntheses of 2'-Cpep protected nucleosides (A, C, G, and U) has been accomplished on a 0.5 Kg scale. The 2'-Cpep monomers were transformed into 3'-O-phosphoramidites for conventional automated solid-phase synthesis. Cost-effective processes for large-scale synthesis of Cpep monomers and initial automated solid-phase synthesis are demonstrated.

Acrylic Resins↗
PubMed2005

Frequency of truly cryptic subtelomere abnormalities--a study of 534 patients and literature review.

Frequency of truly cryptic subtelomere abnormalities - a study of 534 patients and literature review. Unbalanced subtelomere chromosome rearrangements are a significant cause of mental retardation with approximately 5% of over 3000 affected individuals tested worldwide having a chromosome rearrangement of this type. Many of these abnormalities are detectable using routine karyotyping at the 550 band level and therefore are not considered to be cryptic. The frequency of truly cryptic subtelomere abnormality should be less than 5% but has not been established. In this study, we defined 'cryptic abnormality' as one not detectable at the 550 band level on routine karyotyping. Using this as one of the selection criteria, we have studied 534 individuals with mental retardation/ developmental delay (MR/DD) and referred for subtelomere study by clinical geneticists. We have identified seven cases with cryptic subtelomere abnormalities. The clinical features of the seven abnormal cases are summarized. Literature review identified five publications on the identification of subtelomere abnormalities which used similar recruitment criteria: (a) normal karyotype at the 550 band level and (b) subjects were selected for subtelomere studies. Combining the data from these studies with those of the current study, 1154 patients were tested and 30 subtelomere abnormalities were identified. We estimate the frequency of truly cryptic subtelomere abnormality to be approximately 2.6% (30/1154) in children with MR/DD who are referred for subtelomere study.

Abnormalities, Multiple↗
PubMed2004

Education, socioeconomic and lifestyle factors, and risk of coronary heart disease: the PRIME Study.

BACKGROUND: Socioeconomic differentials have been described in the risk of coronary heart disease (CHD) but the extent to which these differentials are explained by lifestyle factors has been examined to a lesser degree. We have examined the contribution of socio-economic factors to risk of CHD in a large cohort study in France and Northern Ireland. METHODS: In all, 10 593 men aged 50-59 years were examined between 1991 and 1994 in centres in Northern Ireland, Lille, Strasbourg, and Toulouse. Details were obtained for a number of socio-economic indicators from the men at the baseline examination. Men were also screened for evidence of CHD and followed annually by questionnaire for incident cases of coronary disease. Coronary events (coronary deaths, myocardial infarction, and angina) were documented by clinical records and were reviewed by an independent medical committee. RESULTS: In all, 842 men (8%) showed some evidence of CHD at screening examination and these men were more likely to be living in poorer material circumstances, be unemployed, or have had less full-time education than men without CHD at screening in both France and Northern Ireland. These relationships persisted following adjustment for all known risk factors for CHD. Among men who were initially free of CHD there were clear socio-economic differentials (years of full-time education, unemployment, and educational level) in the distribution of several risk factors for CHD, notably smoking habit (which differs in France and Northern Ireland), systolic blood pressure, body mass index, and fibrinogen. Total cholesterol in contrast showed no socio-economic differential whilst those with a shorter period of full-time education and the unemployed tended to be high consumers of alcohol. In this cohort of men free of CHD at baseline few socio-economic indicators showed relationships with risk of CHD by 5 years of follow-up. Only years in full education, educational level, and unemployment status when adjusted only for age and country showed significant relationships with CHD risk, but these became non-significant following adjustment for major CHD risk factors. CONCLUSIONS: Socio-economic differentials in long-term risk of CHD are apparent in both cohorts of men from France and Northern Ireland, particularly in men with evidence of CHD at baseline. Among men free of CHD at baseline, although there is strong evidence of socio-economic differentials in cardiovascular risk factors these do not contribute independently to risk of CHD at 5 years of follow-up in this large cohort of men from France and Northern Ireland.

Alcohol Drinking↗
PubMed2004

Effect of porcine parvovirus vaccination on the development of PMWS in segregated early weaned pigs coinfected with type 2 porcine circovirus and porcine parvovirus.

The objectives of this study were to determine if coinfection of segregated early weaned (SEW) pigs with porcine circovirus type 2 (PCV2) and porcine parvovirus (PPV) induces an increase in the incidence of post-weaning multisystemic wasting syndrome (PMWS) compared to singular PCV2 infection, and to determine if vaccination against PPV protects pigs against PMWS associated with PCV2/PPV coinfection in SEW pigs. Seventy, 3-week-old, SEW pigs were randomly assigned to one of the five groups. Pigs in group 1 (n = 14) served as the negative controls, group 2 pigs (n = 14) were inoculated with PCV2, group 3 pigs (n = 12) were inoculated with PPV, groups 4 (n = 16) and 5 (n = 14) pigs were inoculated with both PCV2 and PPV. Pigs in groups 1-3 and 5 were vaccinated with two doses of a killed parvovirus-leptospira-erysipelothrix (PLE) vaccine prior to inoculation. The PCV2/PPV-coinfected pigs (groups 4 and 5) had significantly (P < 0.05) higher and more persistent fevers than the singular PCV2-infected pigs. One pig in each of the coinfected groups developed clinical disease (fever, respiratory disease, jaundice, weight loss) consistent with PMWS. Lymphoid depletion was significantly (P < 0.05) more severe in the dually-infected pigs at 42 days post-inoculation (DPI). Vaccinated, coinfected pigs (group 5) remained viremic significantly (P < 0.05) longer and had higher copy numbers of genomic PCV2 DNA in sera at 28, 35, and 42 DPI compared to the unvaccinated coinfected pigs (group 4). PPV-viremia was detected only in the unvaccinated group 4 pigs. PLE-vaccination prevented PPV-viremia but did not prevent clinical PMWS or reduce the severity of lymphoid depletion in PCV2/PPV-coinfected pigs. Evidence of increased incidence of clinical PMWS due to vaccination was not observed in this model.

Animals↗
PubMed2004

A review of isolated third nerve palsy without subarachnoid hemorrhage using computed tomographic angiography as the first line of investigation.

INTRODUCTION: Digital subtraction angiography is recognized as the standard investigation for isolated third nerve palsy thought to be caused by an expanding aneurysm. We reviewed our experience in using computed tomographic angiography (CTA) as the first line investigation for patients presenting with isolated third nerve palsy without subarachnoid hemorrhage. METHOD: We retrieved the medical records of 34 patients who had presented with isolated third nerve palsy without associated subarachnoid hemorrhage to our institution between January 1998 and July 2001. The clinical history, course and outcome as well as the radiological data was reviewed. RESULTS: A total of nine structural lesions (26%) were noted as the etiology of the third nerve palsy. All of the five posterior communicating artery aneurysms were picked up by the CTA. Neither the presence nor the absence of painful complete third nerve palsy was of diagnostic value for intracranial aneurysm. CONCLUSION: A good quality CTA is sufficient to detect a compressive aneurysm and may detect other structural lesions. This allows neurosurgeons to plan the management of patients with isolated third nerve palsy. Patients in whom CTA results are inconclusive should be further investigated with catheter angiography.

Adolescent↗
PubMed2004

Isolation and characterization of the CD133+ precursors from the ventricular zone of human fetal brain by magnetic affinity cell sorting.

A fast and effective method to enrich large number of neural precursors from the ventricular zone of human fetus by magnetic affinity cell sorting (MACS) is reported. After incubation with phycoerythrin (PE)-conjugated anti-CD133 antibodies and anti-PE magnetic beads followed by one cycle of MACS, CD133(+) cells were harvested at 85% purity as confirmed by flow-cytometry and immunocytochemistry. In contrast to CD133(-) cells, these CD133(+) cells initiated primary and secondary neurospheres in culture, and the progeny of sorted cells could be differentiated into both neurons and glia, indicating that these highly enriched cells are capable of self-renewal and multi-lineage potential.

AC133 Antigen↗
PubMed2004

Comparative disposition of [14C]ertapenem, a novel carbapenem antibiotic, in rat, monkey and man.

1. The disposition and metabolism of ertapenem, a carbapenem antibiotic, was examined in rat, monkey and man. Sprague-Dawley rats and Rhesus monkeys were given, by intravenous administration, radiolabelled doses of ertapenem (60 and 30 mg kg(-1), respectively), and healthy normal volunteers received a single fixed dose of 1000 mg. Urine and faeces were collected for determination of total radioactivity. 2. In healthy volunteers, [14C]ertapenem was eliminated by a combination of hydrolytic metabolism to a beta-lactam ring-opened derivative and renal excretion of unchanged drug. Approximately equal amounts were excreted as a beta-lactam ring-opened metabolite and unchanged drug (36.7 and 37.5% of dose, respectively). A secondary amide hydrolysis product accounted for about 1% of the dose in man. About 10% of the administered radioactivity was recovered in faeces, which suggested that a minor fraction underwent biliary and/or intestinal excretion. 3. In animals, a greater fraction of the dose was eliminated via metabolism; excretion of unchanged drug accounted for 17 and 5% of dose in rats and monkeys, respectively. In monkeys, the beta-lactam ring-opened and amide hydrolysis metabolites accounted for 74.8 and 7.59% of the dose, respectively, whereas in rats, these metabolites accounted for 31.9 and 20% of dose, respectively. 4. In vitro studies with fresh rat tissue homogenates indicated that lung and kidney were the primary organs involved in mediating formation of the beta-lactam ring-opened metabolite. The specific inhibitor of dehydropeptidase-I, cilastatin, inhibited the in vivo and in vitro metabolism of ertapenem in rats, which suggested strongly that the hydrolysis of ertapenem in lung and kidney was mediated by this enzyme.

Adult↗
PubMed2004

The utility of structure-activity relationship (SAR) models for prediction and covariate selection in developmental toxicity: comparative analysis of logistic regression and decision tree models.

Structure-activity relationship (SAR) models can be used to predict the biological activity of potential developmental toxicants whose adverse effects include death, structural abnormalities, altered growth and functional deficiencies in the developing organism. Physico-chemical descriptors of spatial, electronic and lipophilic properties were used to derive SAR models by two modeling approaches, logistic regression and Classification and Regression Tree (CART), using a new developmental database of 293 chemicals (FDA/TERIS). Both single models and ensembles of models (termed bagging) were derived to predict toxicity. Assessment of the empirical distributions of the prediction measures was performed by repeated random partitioning of the data set. Results showed that both the decision tree and logistic regression derived developmental SAR models exhibited modest prediction accuracy. Bagging tended to enhance the prediction accuracy and reduced the variability of prediction measures compared to the single model for CART-based models but not consistently for logistic-based models. Prediction accuracy of single logistic-based models was higher than single CART-based models but bagged CART-based models were more predictive. Descriptor selection in SAR for the understanding of the developmental mechanism was highly dependent on the modeling approach. Although prediction accuracy was similar in the two modeling approaches, there was inconsistency in the model descriptors.

Animals↗
PubMed2004

The selenium requirement of the puppy.

Current selenium (Se) recommendations for the puppy are based on extrapolation from other species (0.11 mg Se/kg diet). The purpose of this study was to experimentally determine the Se requirement in puppies. Thirty beagle puppies (average = 8.8 weeks old) were utilized in a randomized complete block design with age, litter and gender used as blocking criteria. Puppies were fed a low Se (0.04 mg Se/kg diet) torula yeast-based diet for 14 days (pre-test period) after which this same diet was supplemented with five levels of Na2SeO3 for 21 days (experimental period) to construct a response curve (0, 0.13, 0.26, 0.39 or 0.52 mg Se/kg diet). Response variables included Se concentrations and Se-dependent glutathione peroxidase activities (GSHpx) in serum as well as serum total triiodothyronine (TT3), serum total thyroxine (TT4) and serum free T4 (FT4). No significant changes in food intake and body weight gain occurred, and no clinical signs of Se deficiency were observed. A breakpoint for serum GSHpx could not be determined in our study due to analytical difficulties. A broken-line, two-slope response in serum Se occurred with a breakpoint at 0.17 mg Se/kg diet. When Se from the basal diet was added to this estimate, the breakpoint for serum Se equated to 0.21 mg Se/kg diet. TT3 increased linearly with increasing Se intake, whereas TT4 was unchanged. However, the ratio of TT4 : TT3 decreased linearly in response to supplemental Se. In summary, although we estimated the selenium requirement for the puppy based on serum Se, our 0.21 mg Se/kg diet estimate is higher than that seen for adult dogs, kittens, rats or poultry (0.13, 0.15, 0.15 and 0.15 mg Se/kg diet respectively). This difference may be due to the fact that GSHpx was used as the biomarker of Se status.

Animal Nutritional Physiological Phenomena↗
PubMed2004

Vaginal leucocyte counts in women with bacterial vaginosis: relation to vaginal and cervical infections.

OBJECTIVES: To evaluate whether an elevated vaginal leucocyte count in women with bacterial vaginosis (BV) predicts the presence of vaginal or cervical infections, and to assess the relation of vaginal WBC counts to clinical manifestations. METHODS: We retrospectively analysed the relation of vaginal leucocyte counts to vaginal and cervical infections and to clinical manifestations in non-pregnant women diagnosed with BV at an STD clinic visit. RESULTS: Of 296 women with BV studied, the median age was 24 years and 81% were African-American. Elevated vaginal leucocyte counts were associated with objective signs of vaginitis and cervicitis and also predicted candidiasis (OR 7.9, 95% CI 2.2 to 28.9), chlamydia (OR 3.1, 95% CI 1.4 to 6.7), gonorrhoea (OR 2.7, 95% CI 1.3 to 5.4), or trichomoniasis (OR 3.4, 95% CI 1.6 to 7.3). In general, as a screening test for vaginal or cervical infections, vaginal leucocyte count had moderate sensitivities and specificities, low positive predictive values, and high negative predictive values. CONCLUSIONS: An elevated vaginal leucocyte count in women with BV was a strong predictor of vaginal or cervical infections. Vaginal leucocyte quantification may provide an alternative approach to assessing need for empirical therapy for chlamydia and gonorrhoea, particularly in resource-limited high STD risk settings that provide syndromic management.

Adolescent↗
PubMed2004

Experimental reproduction of postweaning multisystemic wasting syndrome in pigs by dual infection with Mycoplasma hyopneumoniae and porcine circovirus type 2.

The objectives of this study were to investigate the interactions between Mycoplasma hyopneumoniae and porcine circovirus type 2 (PCV2) and to establish a model for studying the pathogenesis of and testing intervention strategies for the control of PCV2-associated porcine respiratory disease complex (PRDC). Sixty-seven pigs were randomly assigned to four groups. Group 1 (n=17) pigs served as controls, group 2 (n=17) pigs were inoculated with M. hyopneumoniae, group 3 (n=17) pigs were dual infected with M. hyopneumoniae and PCV2, and group 4 (n=16) pigs were inoculated with PCV2. Pigs were inoculated intratracheally with M. hyopneumoniae at 4 weeks of age followed by intranasal inoculation with PCV2 at 6 weeks of age. Dual-infected pigs had moderate dyspnea, lethargy, and reduced weight gain. The overall severity of macroscopic lung lesions, PCV2-associated microscopic lesions in lung and lymphoid tissues, and the amount of PCV2-antigen associated with these lesions were significantly (P <0.05) higher in dual-infected pigs compared with all other groups. Four of 17 (23.5%) dual-infected pigs had decreased growth rate and severe lymphoid depletion and granulomatous lymphadenitis associated with high amounts of PCV2-antigen consistent with postweaning multisystemic wasting syndrome (PMWS). PCV2-antigen in lung tissue was most often associated with M. hyopneumoniae-induced peribronchial lymphoid hyperplasia, suggesting that this is an important site for PCV2 replication in the lung. This study indicates that M. hyopneumoniae potentiates the severity of PCV2-associated lung and lymphoid lesions, increases the amount and prolongs the presence of PCV2-antigen, and increases the incidence of PMWS in pigs.

Animals↗
PubMed2004

Use of chemical characteristics to predict the relative bioavailability of supplemental organic manganese sources for broilers.

Twelve organic Mn sources and MnSO4 were evaluated by polarographic analysis and via solubility in buffers (pH 5 and 2) and deionized water. Fractions from solubility tests were evaluated by gel filtration chromatography for structural integrity. Organic Mn sources included five Mn methionine complexes (Mn Met A to Mn Met E), two Mn proteinates (Mn Pro A and Mn Pro B), and five Mn amino acids (Mn AA A to Mn AA E). Sources varied considerably in chemical characteristics. Chelation strength (Qf) ranged from weak (1.9 Qf-values) to strong complexes (115.4 Qf-values). No complexed Mn was found in filtrates at pH 2.0 or 5.0. A 42-d bioassay was used to estimate relative bioavailability of Mn sources for chicks fed diets supplemented with 60, 120, or 180 mg Mn/kg. Bone Mn, heart Mn, heart manganese-superoxide dismutase activity (MnSOD), and heart MnSOD mRNA increased (P < 0.001) as dietary Mn increased. Only heart MnSOD mRNA tended (P < 0.10) to differ among dietary Mn sources. For bioassays of Mn, the MnSOD mRNA level in heart was more sensitive than the MnSOD activity in heart or other indices. Relative to MnSO4 (assigned 100%), slope ratios of MnSOD mRNA levels in heart gave bioavailabilities of 99, 132, and 113% for Mn Met E, Mn AA B, and Mn AA C sources with weak, moderate, and strong chelation strength, respectively. The bioavailability of Mn was more closely related to chelation strength as measured by polarography than to chemical traits assessed by solubility or structural integrity.

Animal Feed↗
PubMed2003

TRPV1 receptors mediate particulate matter-induced apoptosis.

Exposure to airborne particulate matter (PM) is a world-wide health problem mainly because it produces adverse cardiovascular and respiratory effects that frequently result in morbidity. Despite many years of epidemiological and basic research, the mechanisms underlying PM toxicity remain largely unknown. To understand some of these mechanisms, we measured PM-induced apoptosis and necrosis in normal human airway epithelial cells and sensory neurons from both wild-type mice and mice lacking TRPV1 receptors using Alexa Fluor 488-conjugated annexin V and propidium iodide labeling, respectively. Exposure of environmental PMs containing residual oil fly ash and ash from Mount St. Helens was found to induce apoptosis, but not necrosis, as a consequence of sustained calcium influx through TRPV1 receptors. Apoptosis was completely prevented by inhibiting TRPV1 receptors with capsazepine or by removing extracellular calcium or in sensory neurons from TRPV1(-/-) mice. Binding of either one of the PMs to the cell membrane induced a capsazepine-sensitive increase in cAMP. PM-induced apoptosis was augmented upon the inhibition of PKA. PKA inhibition on its own also induced apoptosis, thereby suggesting that this pathway may be endogenously protective against apoptosis. In summary, it was found that inhibiting TRPV1 receptors prevents PM-induced apoptosis, thereby providing a potential mechanism to reduce their toxicity.

Air Pollutants↗
PubMed2003

Vanilloid receptor activation by 2- and 10-microm particles induces responses leading to apoptosis in human airway epithelial cells.

Exposure to airborne particulate matter (PM) is associated with increased mortality and morbidity. It has been previously shown that PMs and synthetic particles (PC10 and PC2) that have similar characteristics to PMs induced depolarizing currents and increases in intracellular calcium ([Ca2+]i) in capsaicin- and acid-sensitive sensory neurons and in TRPV1-expressing HEK 293 cells. To determine whether such mechanisms also underlie PM-induced toxicity in epithelial cells lining the human airways, we tested the responses of PCs on BEAS-2B (immortalized human bronchial epithelial cells), NHBE (normal human bronchial/tracheal epithelial cells), and SAEC (normal human small airway epithelial cells from the distal airways). RT-PCR revealed that all these cell types expressed TRPV1 (VR1), ASIC1a, and ASIC3 subunits of proton-gated ion channels. Calcium imaging studies revealed that in all three cell types approximately 30% were activated by both capsaicin and acid. In these cells, PCs induced an increase in [Ca2+]i that was inhibited by capsazepine, a TRPV1 antagonist, and/or by amiloride, an ASIC antagonist. The capsazepine-sensitive contribution to PC-induced increases in [Ca2+]i was approximately 70%. Measurements of apoptosis revealed that exposure to PCs induced a time-dependent increase in the number of apoptotic cells. After incubation for 24 (PC10) or 48 h (PC2) approximately 60% of these cells were apoptotic. Pretreatment with capsazepine as well as removal of external calcium completely (approximately 100%) prevented PC-induced apoptosis. These data suggest that pharmacological inhibition of calcium-permeable vanilloid receptors could be used to prevent some of the pathological actions of PMs.

Air Pollutants↗
PubMed2003

HIV insertions within and proximal to host cell genes are a common finding in tissues containing high levels of HIV DNA and macrophage-associated p24 antigen expression.

HIV integration within host cell genomic DNA is a requisite step of the viral infection cycle. Yet, characteristics of the sites of provirus integration within the host genome remain obscure. The authors present evidence that in diseased tissues showing a high level of HIV DNA and macrophage-associated HIV p24 antigen expression from end stage forms of HIV disease, HIV-1 integration sites were favored within genes and transcriptionally active host cell genomic loci. Using an inverse PCR (IPCR) technique that identified dominant integrated forms of HIV, clonal IPCR products were isolated from AIDS dementia, AIDS lymphoma, and angioimmunoblastic lymphadenopathy tissues. Thirty of 34 disease-associated HIV-1 insertions were identified within annotated and hypothetical genes, an unexpected but highly nonrandom genetic coding region association (p <.026). The 1% sensitivity thresholds used for HIV IPCR suggested some form of selective expansion of cells containing these HIV proviruses. Consistent with this interpretation were the HIV-1 insertion sites identified within introns of genes that encoded for factors associated with signal transduction, apoptosis, and transcription regulation. In addition, HIV-1 proviruses were frequently found proximal to genes that encoded for receptor-associated, signal transduction-associated, transcription-associated, and translation-associated proteins. HIV-1 integration within host cell genomic DNA potentially represents a significant insertional mutagenic event. In certain cases, provirus insertions may mediate the dysregulation of specific gene expression events, providing mechanisms contributing to the pathogenesis associated with certain AIDS-related diseases.

Chromosomes, Human↗
PubMed2003

Phase II study of the efficacy and safety of cisplatin-epinephrine injectable gel administered to patients with unresectable hepatocellular carcinoma.

PURPOSE: To study the efficacy and safety of percutaneous cisplatin-epinephrine (CDDP-EPI) injectable gel in patients with localized unresectable hepatocellular carcinoma (HCC). PATIENTS AND METHODS: Eligible patients had histologically proven HCC, no prior treatment except for surgery, and no more than three tumors (each measured < or = 7 cm, total tumor volume < or = 200 cm(3)). They were treated percutaneously under ultrasound or computed tomography (CT) guidance, with up to 10 mL of CDDP-EPI gel (1 mL contains 4 mg of CDDP and 0.1 mg of EPI) per treatment and four treatments in 6 weeks to a maximum of eight treatments. The primary end points were tumor response, defined by change of percentage of tumor necrosis according to CT criteria, and safety. Survival parameters were secondary end points. RESULTS: From June 1997 to April 2000, 58 patients (median age, 65 years) entered the study. All patients were assessable for safety, and 51 were assessable for efficacy. The median number of treatments was four (range, one to eight treatments). Objective response rate was 53% (27 of 51 patients), including 16 complete and 11 partial responses. Of the 27 responders, 14 (52%) subsequently developed progressive disease, but in most of them (93%), a new tumor arose at untreated liver sites. Median survival was 27 months (range, 18.4 to 35.7 months). The 1-, 2-, and 3-year survival rates were 79%, 56%, and 14% respectively. The procedure was well tolerated with only minor side effects. CONCLUSION: Percutaneous local ablation with CDDP-EPI injectable gel can induce significant tumor necrosis and local control for localized unresectable HCC, and the treatment is well tolerated.

Adult↗