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Biomedical subjects

S Zhang

Publications and source records attributed to S Zhang.

At least 37 records · Page 2Linked to original sources

Insulin stimulates arterial neointima formation in normal rats after balloon injury.

AIM: Insulin resistance in patients is associated with increased atherosclerosis and arterial restenosis. It is thought that the concomitant hyperinsulinaemia exacerbates vascular disease because resistance to insulin-induced glucose disposal is associated with resistance to certain effects of insulin which inhibit, but with no resistance to other effects which promote, neointimal hyperplasia. We sought to determine the net effect of hyperinsulinaemia on neointimal hyperplasia in normal animals. METHODS: Rats were infused with or without insulin for 16 days and the carotid artery injured by balloon catheter on day 2. RESULTS: Steady-state serum insulin concentrations were 0.56 +/- 0.04 and 1.25 +/- 0.05 nm for control and hyperinsulinaemic rats respectively (p < 0.01). Systolic blood pressures, weights and serum glucose levels were not affected by hyperinsulinaemia. Fourteen days after injury, the neointima-to-media area ratio was 0.72 +/- 0.07 and 1.39 +/- 0.15 for control and hyperinsulinaemic rats respectively (p < 0.05). Media area was unaffected by hyperinsulinaemia. CONCLUSIONS: The effects of hyperinsulinaemia which promote neointimal hyperplasia after balloon injury of rat carotid artery predominate over the effects which inhibit it even in normal animals.

Angioplasty, Balloon↗

Effect of primer selection on estimates of GB virus C (GBV-C) prevalence and response to antiretroviral therapy for optimal testing for GBV-C viremia.

GB virus C (GBV-C; also called hepatitis G virus) is a common cause of infection associated with prolonged survival among HIV-infected individuals. The prevalences of GBV-C viremia vary widely in different studies, and there has been poor agreement among different laboratories performing GBV-C RNA detection in quality control studies. To determine the optimal method of measuring GBV-C RNA in clinical samples, samples obtained from 939 HIV-infected subjects were studied using reverse transcription (RT)-PCR methods amplifying four separate regions of the GBV-C genome. Primers amplifying the E2 coding region were 100% specific; however, their sensitivity was only 76.6%. In contrast, primers amplifying three additional conserved regions of the GBV-C genome (the 5' nontranslated region and the nonstructural protein-coding regions 3 and 5A) were more sensitive but produced higher rates of false-positive results. Using low-specificity primer sets influenced the significance of association between GBV-C viremia and response to antiretroviral therapy. Using a quantitative GBV-C RNA method, the GBV-C RNA concentration did not correlate with baseline or set point HIV RNA levels; however, a correlation between negative, low, and high GBV-C RNA levels and increasing reduction in HIV RNA following antiretroviral therapy was observed. Subjects with both GBV-C E2 antibody and viremia had significantly lower GBV-C RNA levels than did viremic subjects without E2 antibody. These studies demonstrate that accurate detection of GBV-C RNA by nested RT-PCR requires the use of primers representing multiple genome regions. Analyses based on testing with single primers do not lead to reliable conclusions about the association between GBV-C infection and clinical outcomes.

Anti-HIV Agents↗

Differentiating sex chromosomes of the dioecious Spinacia oleracea L. (spinach) by FISH of 45S rDNA.

Spinacia oleracea L. (spinach) is a dioecious species with both male and female plants having 2n = 2x = 12 chromosomes, consisting of two large metacentrics, two long subtelocentrics, two short subtelocentrics, two acrocentrics, and four submetacentrics. The location of 45S rDNA was investigated on metaphase chromosomes using fluorescence in situ hybridization (FISH). The numbers of 45S rDNA foci in diploid sets of chromosomes from females was six and from males was five. All the fluorescent foci lay in secondary constrictions and the satellites. Our results indicate that an XY-type sex chromosome system could be present in spinach where the Y chromosome lacks a 45S RNA focus.

Chromosomes, Plant↗

Duplications of proximal 16q flanked by heterochromatin are not euchromatic variants and show no evidence of heterochromatic position effect.

Extra euchromatic material was found within the major heterochromatic block of chromosome 16 (16qh) in one de novo case and seven members of two families. In contrast to the euchromatic variants of chromosome 9 (9qh), which are derived from pericentromeric euchromatin, molecular cytogenetics confirmed that these duplications were of 16q11.2-->q12.2 in the de novo case, of 16q11.2-->q13 in three members of family 1 and 16q11.2-->q12.1 in four members of family 2. The duplication had arisen as a post-zygotic mitotic event in the mother of family 1 and been transmitted paternally in family 2. An insertional mechanism of origin is proposed for the duplications in case 1 and family 1. Expression at the 16q13 matrix metalloproteinase-2 (MMP2)locus in families 1 and 2 was proportional to genomic copy number and not therefore consistent with position effect silencing due to the flanking blocks of heterochromatin. We conclude that proximal 16q duplications within 16qh are not novel euchromatic variants but associated with a variable phenotype including developmental delay, speech delay, learning difficulties and behavioural problems. The behavioural problems in families ascertained through affected children are much less severe than those encountered in previous patients ascertained as adults.

Adolescent↗

Detection and characterization of naturally acquired West Nile virus infection in a female wild turkey.

An adult female wild turkey exhibiting disorientation and failure to flee when approached was submitted to the Mississippi Veterinary Research and Diagnostic Laboratory. Gross pathologic examination revealed evidence of dehydration and the presence of modest numbers of adult nematodes in the small intestine. Histologic examination revealed extensive multifocal perivascular lymphocytic infiltration in brain, marked heterophilic hyperplasia in bone marrow, and multifocal interstitial lymphocytic infiltration in heart, pancreas, ventriculus, and skeletal muscles. West Nile virus (WNV) was isolated from the brain, lung, and kidney tissues using cultured Vero cells. Higher copies of viral RNA were detected from brain, lung, and kidney than from heart, liver, or spleen by quantitative real-time reverse transcription-polymerase chain reaction (RRT-PCR) analysis. Immunohistochemical (IHC) analysis detected WNV antigen in various tissues including neurons, kidney, respiratory tract epithelium, heart, and bone marrow. On the basis of the data from this investigation, it is concluded that WNV caused encephalitis along with many other pathologic changes in the affected wild turkey.

Animals↗

Phase I and pharmacological study of the farnesyltransferase inhibitor tipifarnib (Zarnestra, R115777) in combination with gemcitabine and cisplatin in patients with advanced solid tumours.

This phase I trial was designed to determine the safety and maximum tolerated dose (MTD) of tipifarnib in combination with gemcitabine and cisplatin in patients with advanced solid tumours. Furthermore, the pharmacokinetics of each of these agents was evaluated. Patients were treated with tipifarnib b.i.d. on days 1-7 of each 21-day cycle. In addition, gemcitabine was given as a 30-min i.v. infusion on days 1 and 8 and cisplatin as a 3-h i.v. infusion on day 1. An interpatient dose-escalation scheme was used. Pharmacokinetics was determined in plasma and white blood cells. In total, 31 patients were included at five dose levels. Dose-limiting toxicities (DLTs) consisted of thrombocytopenia grade 4, neutropenia grade 4, febrile neutropenia grade 4, electrolyte imbalance grade 3, fatigue grade 3 and decreased hearing grade 2. The MTD was tipifarnib 200 mg b.i.d., gemcitabine 1000 mg m(-2) and cisplatin 75 mg m(-2). Eight patients had a confirmed partial response and 12 patients stable disease. No clinically relevant pharmacokinetic interactions were observed. Tipifarnib can be administered safely at 200 mg b.i.d. in combination with gemcitabine 1000 mg m(-2) and cisplatin 75 mg m(-2). This combination showed evidence of antitumour activity and warrants further evaluation in a phase II setting.

Administration, Oral↗

Effects of human soluble BAFF synthesized in Escherichia coli on CD4+ and CD8+ T lymphocytes as well as NK cells in mice.

B cell-activating factor belonging to the TNF family (BAFF, also called BLyS, TALL-1, zTNF-4, or THANK) is an important survival factor for B lymphocytes. In this study, we injected mouse abdominal cavity with human soluble BAFF (hsBAFF, 0.01, 0.1, 0.5, 2 mg/kg body mass) synthesized in Escherichia coli. On the 8th day after injection, we investigated the effects of hsBAFF on immune functional activities of splenic B lymphocytes, CD4(+) and CD8(+) T lymphocytes and natural killer (NK) cells in mice. The results showed that B lymphocyte proliferation significantly increased in hsBAFF-treated groups with dosages of 0.1 mg/kg (p<0.05), 0.5 and 2 mg/kg (p<0.01). We observed a dose-dependent increase of CD4(+) T lymphocyte percentage and significantly higher values in 0.5 and 2 mg/kg hsBAFF-treated groups (p<0.05 and p<0.001, respectively) compared to control group, but CD8(+) T lymphocyte percentage remained unchanged. The ratio of CD4(+) to CD8(+) T lymphocytes rose with increasing hsBAFF dosage (p<0.05 for 2 mg/kg hsBAFF vs. control). Significantly stronger NK cell activities were found in 0.5 and 2 mg/kg hsBAFF-treated groups (p<0.05). The main finding of this study is that the hsBAFF can enhance immune responses in the body by increasing B lymphocyte and CD4(+) T lymphocyte function as well as elevating NK cell activity.

Animals↗

Endogenous ATP involvement in mustard-oil-induced central sensitization in trigeminal subnucleus caudalis (medullary dorsal horn).

Central sensitization represents a sustained hypersensitive state of dorsal horn nociceptive neurons that can be evoked by peripheral inflammation or injury to nerves and tissues. It reflects neuroplastic changes such as increases in neuronal spontaneous activity, receptive field size, and responses to suprathreshold stimuli and a decrease in activation threshold. We recently demonstrated that purinergic receptor mechanisms in trigeminal subnucleus caudalis (Vc; medullary dorsal horn) are also involved in the initiation and maintenance of central sensitization in brain stem nociceptive neurons of trigeminal subnucleus oralis. The aim of the present study was to investigate whether endogenous ATP is involved in the development of central sensitization in Vc itself. The experiments were carried out on urethan/alpha-chloralose anesthetized and immobilized rats. Single neurons were recorded and identified as nociceptive-specific (NS) in the deep laminae of Vc. During continuous saline superfusion (0.6 ml/h it) over the caudal medulla, Vc neuronal central sensitization was readily induced by mustard oil application to the tooth pulp. However, this mustard-oil-induced central sensitization could be completely blocked by continuous intrathecal superfusion of the wide-spectrum P2X receptor antagonist pyridoxal-phosphate-6-azophenyl-2, 4-disulphonic acid tetra-sodium (33-100 microM) and by apyrase (an ectonucleotidase enzyme, 30 units/ml). Superfusion of the selective P2X1, P2X3 and P2X(2/3) receptor antagonist 2',3'-O-(2,4,6-trinitrophenyl) adenosine 5'-triphosphate (6-638 microM) partially blocked the Vc central sensitization. The two P2X receptor antagonists did not significantly affect the baseline nociceptive properties of the Vc neurons. These findings implicate endogenous ATP as an important mediator contributing to the development of central sensitization in nociceptive neurons of the deep laminae of the dorsal horn.

Action Potentials↗

Synthesis of a novel PEG-block-poly(aspartic acid-stat-phenylalanine) copolymer shows potential for formation of a micellar drug carrier.

A novel functionalised copolymer with three polymeric components, poly(ethylene glycol)-block-poly(aspartic acid-stat-phenylalanine), PEG-P(asp-phe), was synthesised and investigated for its potential to form micelles via ionic interactions with a model water-soluble drug, diminazene aceturate. Drug-free solutions of structurally related PEG-P(asp-phe) 5:6:4 and PEG-P(asp-phe) 5:4:6 copolymers indicated polymeric aggregation into micellar-type constructs. The size of PEG-P(asp-phe) 5:6:4 micelles was found to be pH and drug content-dependent. The drug-loaded systems existed as discreet units and were fairly uniform in size and shape. More drug could be included in the PEG-P(asp-phe) 5:6:4 micelles as compared to if only interaction with carboxyl groups from aspartic acid units was responsible for micelle formation, indicating the augmentative role of phenylalanine moieties in drug-incorporation. The slower in vitro drug release from PEG-P(asp-phe) 5:6:4 micelles as compared to PEG-Pasp (AB) micelles indicated the role of the phenylalanine moiety in controlling drug release. This study, therefore, confirmed the potential of a novel tri-component copolymer structure, PEG-P(asp-phe), for the formation of polyionic micelles for drug delivery.

Chemical Phenomena↗

Intrinsic spin and orbital angular momentum Hall effect.

A generalized definition of intrinsic and extrinsic transport coefficients is introduced. We show that transport coefficients from the intrinsic origin are solely determined by local electronic structure, and thus the intrinsic spin Hall effect is not a transport phenomenon. The intrinsic spin Hall current is always accompanied by an equal but opposite intrinsic orbital angular momentum Hall current. We prove that the intrinsic spin Hall effect does not induce a spin accumulation at the edge of the sample or near the interface.

Journal Article↗

The Biomolecular Interaction Network Database and related tools 2005 update.

The Biomolecular Interaction Network Database (BIND) (http://bind.ca) archives biomolecular interaction, reaction, complex and pathway information. Our aim is to curate the details about molecular interactions that arise from published experimental research and to provide this information, as well as tools to enable data analysis, freely to researchers worldwide. BIND data are curated into a comprehensive machine-readable archive of computable information and provides users with methods to discover interactions and molecular mechanisms. BIND has worked to develop new methods for visualization that amplify the underlying annotation of genes and proteins to facilitate the study of molecular interaction networks. BIND has maintained an open database policy since its inception in 1999. Data growth has proceeded at a tremendous rate, approaching over 100 000 records. New services provided include a new BIND Query and Submission interface, a Standard Object Access Protocol service and the Small Molecule Interaction Database (http://smid.blueprint.org) that allows users to determine probable small molecule binding sites of new sequences and examine conserved binding residues.

Animals↗

ADHD Rating Scale IV: psychometric properties from a multinational study as a clinician-administered instrument.

The development of rating scales for attention-deficit/hyperactivity disorder (ADHD) has traditionally focused on parent-or teacher-rated scales. However, clinician-based instruments are valuable tools for assessing ADHD symptom severity. The ADHD Rating Scale IV (ADHD RS), clinician administered and scored, has been validated as a useful instrument to assess ADHD symptoms among American children and adolescents. In this study, we assessed the psychometric properties of the scale in a recent clinical trial conducted mainly in Europe with over 600 children and adolescents diagnosed with ADHD. The trial was conducted in 11 European countries plus Australia, Israel, and South Africa. Results based on data in the study indicate that this version of the scale has acceptable psychometric properties including inter-rater reliability, test-retest reliability, internal consistency, factor structure, convergent and divergent validity, discriminant validity, and responsiveness. There were low-to-moderate ceiling and floor effects. The psychometric properties were comparable with other validated scales for assessing ADHD symptom severity. These results were consistent across the 14 countries participating in this trial. Overall, the data from this study support the use of the ADHD RS as a clinician-rated instrument for assessing the severity of ADHD symptoms in children and adolescents in Europe.

Adolescent↗

Expression and immunolocalisation of odorant-binding and chemosensory proteins in locusts.

We have identified, cloned and expressed a new chemosensory protein (CSP) in the desert locust Schistocerca gregaria belonging to a third sub-class of these polypeptides. Polyclonal antibodies stained a band of 14 kDa, as expected, in the extracts of antennae and palps of the adults, but not in the 4th and 5th instars. In the related species Locusta migratoria, instead, the same antibodies cross-reacted only with a band of apparent molecular mass of 35 kDa in the extract of 1st-5th instars, but not in the adults. The recombinant protein binds the fluorescent probe N-phenyl-1-naphthylamine, but none of the compounds so far reported as pheromones for S. gregaria. The expression of the odorant-binding protein (OBP) and of CSPs of sub-classes I and II was also monitored in antennae, tarsi, palpi, wings and other organs of solitary and gregarious locusts in their nymphal and adult stages. OBP was found to be antenna specific, where it is expressed at least from the 3rd instar in both solitary and gregarious locusts. CSPs, instead, appear to be more ubiquitous, with different expression patterns, according to the sub-class. Immunocytochemistry experiments revealed that OBP is present in the sensillum lymph of sensilla trichodea and basiconica, while CSP-I and CSP-III were found in the outer sensillum lymph of sensilla chaetica and in the sub-cuticular space between epidermis and cuticle of the antenna. Sensilla chaetica on other parts of the body showed the same expression of CSP-I as those on the antenna.

1-Naphthylamine↗

Double-antigen sandwich ELISA for detection of antibodies to SARS-associated coronavirus in human serum.

The study presented here was conducted to evaluate the performance of a double-antigen sandwich ELISA to detect antibodies in human serum against the coronavirus associated with severe acute respiratory syndrome (SARS). A recombinant partial nucleocapsid protein of SARS-associated coronavirus was used as a serodiagnostic antigen in the ELISA. A total of 2892 clinical serum samples were tested with the ELISA kit, which positively identified 25 of 35 (71.4%) samples of patients with confirmed SARS infection, 286 of 407 (70%) samples of patients suspected of having SARS, 229 of 302 (75.8%) samples of convalescent SARS patients, and 0 of 544 samples obtained from healthcare workers; only 1 of 1604 clinical samples obtained from patients with other diseases demonstrated a weakly positive result. These results indicate that the double-antigen sandwich ELISA is an effective screening method for the serodiagnosis of SARS-associated coronavirus.

Antibodies, Viral↗

Effects of rapamycin on the arterial inflammatory response in atherosclerotic plaques in Apo-E knockout mice.

Because of its antiproliferative properties and its known effects on plasma lipids, we evaluated the mechanisms underlying the effect of rapamycin (RPM) on endothelial nitric oxide synthase (eNOS) and matrix metalloproteinases in Apo-E knockout mice. Apo-E-/- mice fed a high-cholesterol diet were given RPM (3 mg/kg per day intraperitoneally) or no treatment for 10 weeks (n = 8 each). Blood was drawn for serum lipid analysis. Protein was extracted from the abdominal aortas for Western immunoblotting and zymography. Cellular localization was assessed by histology and immunohistochemistry. The data, expressed as mean +/- SEM, were compared by Student's t test or analysis of variance (ANOVA). Lipid levels at 10 weeks were similar in both groups except for higher triglyceride levels in RPM-treated animals. RPM-treated mice expressed greater amounts of eNOS and p-eNOS compared with controls (P < .05). Akt, p-Akt, Caveolin-1, and p-Caveolin-1 were not significantly affected by RPM treatment. RPM treatment was associated with increased activation of pro-MMP-9, a significant decrease in MMP-2 tissue levels, and corresponding increases in TIMP-2 and TIMP-3 expression. The increased expression and phosphorylation of eNOS with RPM appears to be regulated by mechanisms other than Akt or Caveolin-1. Alterations in eNOS expression, in addition to changes in MMP/TIMP ratios and MMP-2 and MMP-9 activation, may partially explain the changes observed in the aorta of treated Apo-E-/- mice induced by RPM.

Analysis of Variance↗

Clinical study of recombinant adenovirus-p53 (Adp53) combined with hyperthermia in advanced cancer (a report of 15 cases).

The study was to evaluate the efficacy of the Adp53 combined with hyperthermia on advanced cancer. Fifteen patients with advanced cancer were enrolled in this clinical trial. Thirteen patients with recurrent tumours failed in conventional treatments and the two other patients with primary tumour received no treatment before they were enrolled. Recombinant adenovirus-p53 (Adp53) is a E1 substituted replication-incompetent recombinant adenovirus encoding the human wild-type p53 (wtp53) gene. The 15 patients were intra-tumourally injected with Adp53, 1x10(12)vp (virus particle) once a week, with a total of 4-8 times was given. The temperature being set hyperthermia every week 3 days after the injection of Adp53 at 43-44 degrees C using 915 MHz microwave machine for superficial tumour for 1 h or at 42-43 degrees C using 41 MHz radiofrequency machine for deep-seated tumour for 1 h. Among the 15 patients, five concurrently were added with radiotherapy and three were added with cisplatin-based chemotherapy. The treatment achieved CR in two cases, PR in four cases, SD in eight cases and PD in one case and, after the treatment, tumours of two cases disappeared and seven of the other 13 cases (54%) had low-density area (LDA) of more than 50% on CT images in tumours. In the 15 patients, no dose-limiting toxicity and adverse events were noted, except transient fever after Adp53 administration. In conclusion, Adp53 combined with hyperthermia was safe and effective in patients with advanced cancer and p53 gene therapy was potential to thermosensitize in advanced cancer.

Adenoviruses, Human↗

Statistics on cancer in China: cancer registration in 2002.

The objective of this study was to determine how many population-based cancer registries exist in China, what methods are being used, and the statistical data that are available from them, and to identify future needs with respect to technical support. A two-stage survey was conducted in 2002 at provincial and cancer registry level. Based on the questionnaire used in these two stages, the basic distribution and descriptive information on population-based cancer registry practices in China are addressed. There are 48 cancer registries in China, covering 73 million people (5.7% of the total population of China in 2000). The oldest three registries are LinZhou, ShangHai and QiDong. There are marked variations in practice between registries, with respect to data collection, data management and coding. Differences are also found in administrative aspects and sources of financial support. In conclusion, this first national survey of Chinese cancer registry practice provides a benchmark against which development and standardization can be evaluated in the future. The survey suggests that lack of qualified personnel, insufficient funding support and lack of stability of the population are major problems in carrying out registration work in China. It also indicates several ways in which registry practice, and hence availability and quality of incidence and survival data can be improved.

Benchmarking↗

Molecular evidence supporting the neoplastic nature of odontogenic keratocyst: a laser capture microdissection study of 15 cases.

AIMS: The bland histology of odontogenic keratocyst (OKC) belies its capacity for aggressive behaviour. Genetic alterations of OKC have not been well studied. We examined the frequency and pattern of allelic imbalance on five different chromosome regions from 15 patients with OKC. METHODS AND RESULTS: Laser-assisted microdissection was performed on formalin-fixed paraffin-embedded tissue. Polymerase chain reaction analysis of extracted DNA targeted five polymorphic DNA markers (D3S1285, D9S161, D11S1316, D13S290, and TP53) representing chromosome regions 3p14, 9p21, 11q23, 13q12.1 and 17p13, respectively. All 15 cases of OKC were informative at a minimum of three of five loci, with 11 informative on all five loci. Twelve of 15 cases (80%) demonstrated loss of heterozygosity (LOH). Seven cases (47%) showed LOH at more than two DNA loci. The frequency of LOH was 5/11 (45%) at D3S1285, 3/15 (20%) at D9S161, 4/14 (29%) at D11S1316, 8/14 (57%) at D13S290 and 3/15 (20%) at TP53. CONCLUSIONS: The majority of OKCs harbour chromosomal abnormalities. This finding supports the supposition that OKCs are neoplastic. Furthermore, OKCs harbour allelic loss at some of the same loci identified in squamous cell carcinoma. This may aid in explaining the rare occurrence of squamous cell carcinoma arising in OKC.

Alleles↗