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Biomedical subjects

Y Jiang

Publications and source records attributed to Y Jiang.

At least 55 records · Page 3Linked to original sources

The role of the p75 neurotrophin receptor in the morphology of dorsal root ganglion cells in streptozotocin diabetic mice: effects of sciatic nerve crush.

AIMS/HYPOTHESIS: Neuronal dorsal root ganglion (DRG) cells seem to be vulnerable in diabetes. The aim of this study was to determine whether the p75 neurotrophin receptor stimulates perikaryal shrinkage and neuronal death, and further accelerates neuronal DRG cell loss after axotomy in a mouse model of diabetes. METHODS: Nine non-diabetic BALB/c p75(+/+) mice, seven diabetic BALB/c p75(+/+) mice, nine non-diabetic p75(-/-) mice and nine diabetic p75(-/-) mice received a unilateral sciatic nerve crush 1 to 2 days after streptozotocin treatment. Tissues were fixed 28 days later by vascular perfusion, and the volume and number of the fifth lumbar DRG neurons were obtained using assumption-free stereological techniques. RESULTS: In diabetic p75(+/+) mice there was a 9% reduction in the perikaryal volume of the DRG A cells ( p<0.05) and a 10% reduction in the perikaryal volume of the DRG B cells ( p<0.05) on the non-crushed side compared with in non-diabetic p75(+/+) mice. However, neuronal cell number was not reduced. Conversely, no perikaryal shrinkage of A cells or B cells occurred on the non-crushed side in diabetic p75(-/-) mice, and no neuronal cell loss was observed. Following nerve crush, there was a loss of B cells in non-diabetic p75(+/+) mice (37+/-6%) and in diabetic p75(+/+) mice (36+/-4%). In non-diabetic p75(-/-) mice, no neuronal cell loss occurred after crush, whereas in diabetic p75(-/-) mice the loss of B cells (14+/-4%) was small but significant ( p<0.02). CONCLUSIONS/INTERPRETATION: In experimental diabetes the p75 neurotrophin receptor is involved in neuronal DRG cell body shrinkage without loss of neuronal DRG cells. Following sciatic nerve crush, DRG cell loss is not accelerated in diabetic p75(+/+) mice.

Animals↗

How does peripheral lipopolysaccharide induce gene expression in the brain of rats?

Lipopolysaccharide (LPS), the principal cell-wall component of gram-negative bacteria, is responsible for alterations in the central and peripheral tissues associated with gram-negative infections. However, the mechanism by which peripheral LPS cause central effects is not fully known. This study showed that peripheral LPS sequentially increased IL-1beta and iNOS mRNA levels, NO2 level, and CRF mRNA level in the hypothalamic PVN, and corticosterone concentration in blood. Brain-endothelium, but not hypothalamic PVN samples, from LPS injected rats contained ions for LPS lipids, bound BODIPY-LPS (bLPS), and expressed TLR-4, TLP-2 and CD14 mRNAs. This suggests that (1) LPS does not cross the blood-brain barrier, and (2) brain-endothelial cells contain LPS binding sites, TLR-4, TLR-2 and CD14. Systemic LPS injection increased [14C]sucrose uptake, but did not affect [14C]dextran uptake into the brain. Thus, when injected systemically, LPS binds to its receptor and enter the endothelial cells where it increase BBB permeation in a mass-selective manner and triggers a series of signaling events leading to the development of inflammatory response in the brain.

Adrenal Cortex Hormones↗

Two-stage aggregate formation via streams in myxobacteria.

In response to adverse conditions, myxobacteria form aggregates that develop into fruiting bodies. We model myxobacteria aggregation with a lattice cell model based entirely on short-range (nonchemotactic) cell-cell interactions. Local rules result in a two-stage process of aggregation mediated by transient streams. Aggregates resemble those observed in experiment and are stable against even very large perturbations. Noise in individual cell behavior increases the effects of streams and results in larger, more stable aggregates.

Bacterial Physiological Phenomena↗

Absence of antibodies to glutamate receptor type 3 (GluR3) in Rasmussen encephalitis.

OBJECTIVE: To determine the prevalence of serum antibodies to the ionotropic glutamate receptor 3 (GluR3) in patients with Rasmussen encephalitis (RE), a severe epileptic disorder, and to compare with serum from control subjects and patients with intractable epilepsy (IE). METHODS: The authors looked for serum immunoglobulin (Ig) G antibodies to GluR3 in 30 patients with RE, including two patients who had plasma exchange and 12 who had been treated with IV Igs with varying results, and 49 patients with IE and 23 healthy individuals, using ELISA with GluR3B peptide, Western blot analysis of recombinant full-length GluR3, immunoprecipitation of [35S]- and [125I]-labeled GluR3 extracellular domains, immunohistochemistry on rat brain sections, and electrophysiology of GluR3 expressed in Xenopus oocytes. RESULTS: Low levels of antibodies to the GluR3B peptide were detected using ELISA in only 4 of the 79 patients with epilepsy (2 with RE and 2 with IE); binding to GluR3B in other sera was shown to be nonspecific. One other patient with IE had antibodies to recombinant GluR3 on Western blot analysis. However, none of the sera tested precipitated either the [35S]- or the [125I]-labeled GluR3 domains; none bound to rat brain sections in a manner similar to rabbit antibodies to GluR3; and none of the nine sera tested affected the electrophysiologic function of GluR3. CONCLUSIONS: GluR3 antibodies were only infrequently found in Rasmussen encephalitis or intractable epilepsy.

Adolescent↗

Common variants in the 5' region of the leptin gene are associated with body mass index in men from the National Heart, Lung, and Blood Institute Family Heart Study.

Linkage of body mass index (BMI) to a broad region of chromosome 7q22-35 has been reported in multiple studies. We previously published a multipoint LOD score of 4.9 at D7S1804 for BMI from the National Heart, Lung, and Blood Institute Family Heart Study. Leptin (LEP), the human homolog of the mouse obesity (ob) gene, is positioned near the linkage peak and is the most prominent candidate gene in this region. Interest in LEP as a susceptibility gene for human obesity has led to numerous linkage and association studies, but the results of these studies are still controversial. In the present study, we employed family-based tests of association with both a quantitative measure of BMI adjusted for age and sex and a dichotomously defined obesity trait. We genotyped 29 single-nucleotide polymorphisms (SNPs) spanning 240 kb around the LEP gene in the 82 extended pedigrees with the strongest evidence for linkage. When the programs TRANSMIT and FBAT were used, a number of SNPs showed association in men but not women, for both the quantitative and qualitative trait definitions (P<.05). Five SNPs (H1328084, H1328083, H1328082, H1328081, and H1328080) positioned 2 kb beyond the previously defined promoter region showed strong association in single-marker and multiple-marker haplotype analysis. This five-marker haplotype (frequency 49% in this sample) is overtransmitted to obese offspring (P=.00005). All five of these SNPs are predicted to modify transcription-factor binding sites. This may indicate new functional variants in an extended promoter region of LEP.

Body Mass Index↗

Substantial reduction of critical current for magnetization switching in an exchange-biased spin valve.

Great interest in current-induced magnetic excitation and switching in a magnetic nanopillar has been caused by the theoretical predictions of these phenomena. The concept of using a spin-polarized current to switch the magnetization orientation of a magnetic layer provides a possible way to realize future 'current-driven' devices: in such devices, direct switching of the magnetic memory bits would be produced by a local current application, instead of by a magnetic field generated by attached wires. Until now, all the reported work on current-induced magnetization switching has been concentrated on a simple ferromagnet/Cu/ferromagnet trilayer. Here we report the observation of current-induced magnetization switching in exchange-biased spin valves (ESPVs) at room temperature. The ESPVs clearly show current-induced magnetization switching behaviour under a sweeping direct current with a very high density. We show that insertion of a ruthenium layer between an ESPV nanopillar and the top electrode effectively decreases the critical current density from about 10(8) to 10(7) A cm(-2). In a well-designed 'antisymmetric' ESPV structure, this critical current density can be further reduced to 2 x 10(6) A cm(-2). We believe that the substantial reduction of critical current could make it possible for current-induced magnetization switching to be directly applied in spintronic devices, such as magnetic random-access memory.

Journal Article↗

Effective reduction of critical current for current-induced magnetization switching by a Ru layer insertion in an exchange-biased spin valve.

Recently, it has been predicted that a spin-polarized electrical current perpendicular to plane directly flowing through a magnetic element can induce magnetization switching through spin-momentum transfer. In this Letter, the first observation of current-induced magnetization switching (CIMS) in exchange-biased spin valves (ESPVs) at room temperature is reported. The ESPVs show the CIMS behavior under a sweeping dc current with a very high critical current density. It is demonstrated that a thin ruthenium (Ru) layer inserted between a free layer and a top electrode effectively reduces the critical current densities for the CIMS. An "inverse" CIMS behavior is also observed when the thickness of the free layer increases.

Journal Article↗

Precision Zeeman-Stark spectroscopy of the metastable a1[3Sigma+] state of PbO.

The metastable a(1)[(3)Sigma(+)] state of PbO has been suggested as a suitable system in which to search for the electric dipole moment of the electron. We report here the development of experimental techniques allowing high-sensitivity measurements of Zeeman and Stark effects in this system, similar to those required for such a search. We observe Zeeman quantum beats in fluorescence from a vapor cell of PbO, with shot-noise limited extraction of the quantum beat frequencies, high counting rates, and long coherence times. We argue that improvement in sensitivity to the electron electric dipole moment by at least 2 orders of magnitude appears possible using these techniques.

Journal Article↗

In vitro susceptibility of 10 clinical isolates of SARS coronavirus to selected antiviral compounds.

Effective antiviral agents are urgently needed to combat the possible return of severe acute respiratory syndrome (SARS). Commercial antiviral agents and pure chemical compounds extracted from traditional Chinese medicinal herbs were screened against 10 clinical isolates of SARS coronavirus by neutralisation tests with confirmation by plaque reduction assays. Interferon-beta-1a, leukocytic interferon-alpha, ribavirin, lopinavir, rimantadine, baicalin and glycyrrhizin showed antiviral activity. The two interferons were only active if the cell lines were pre-incubated with the drugs 16 h before viral inoculation. Results were confirmed by plaque reduction assays. Antiviral activity varied with the use of different cell lines. Checkerboard assays for synergy were performed showing combinations of interferon beta-1a or leukocytic interferon-alpha with ribavirin are synergistic. Since the clinical and toxicity profiles of these agents are well known, they should be considered either singly or in combination for prophylaxis or treatment of SARS in randomised placebo controlled trials in future epidemics.

Adult↗

T-helper and T-cytotoxic cell subsets monitoring during active cytomegalovirus infection in liver transplantation.

OBJECTIVE: The objectives of this study was to analyze the peripheral blood T-lymphocyte subsets of the Th1-related versus Th2-related cytokines of CD4+ cells, and the Tc1 versus Tc2 cytokines of CD8+ cells liver transplant recipients with versus without active cytomegalovirus (CMV) infection. METHODS: Isolated peripheral blood mononuclear cells (PBMC) were stimulated using PMA/Ionomycin/Monensin. Interleukin (IL)-4 and interferon gamma (IFN-gamma) production by CD4+ and CD8+T cells were determined using fluorescence-activated cell sorter (FACS) analysis. RESULTS: The ratios of CD4/CD8 were significantly lower among active CMV-infected patients. The levels of Th2 and Tc2 cytokines (IL-4) were similar between CMV-infected and uninfected patients. However, the levels of Th1-type and Tc1-type cytokines (IFN-r) were significantly lower among active CMV-infected patients. CONCLUSIONS: Low levels of Th1-type cytokines seem to correlate with active CMV infection in liver transplant recipients.

Antigens, CD↗

Cellular delivery of a double-stranded oligonucleotide NFkappaB decoy by hybridization to complementary PNA linked to a cell-penetrating peptide.

The activation of nuclear factor kappaB (NFkappaB) is a key event in immune and inflammatory responses. In this study, a cell-penetrating transport peptide, transportan (TP) or its shorter analogue TP 10, was used to facilitate the cellular uptake of an NFkappaB decoy. Peptide nucleic acid (PNA) hexamer or nonamer was linked to the transport peptide by a disulfide bond. NFkappaB decoy oligonucleotide consisted of a double-stranded consensus sequence corresponding to the kappaB site localized in the IL-6 gene promoter, 5'-GGGACTTTCCC-3', with a single-stranded protruding 3'-terminal sequence complementary to the PNA sequence was hybridized to the transport peptide-PNA construct. The ability of the transport peptide-PNA-NFkappaB decoy complex to block the effect of interleukin (IL)-1beta-induced NFkappaB activation and IL-6 gene expression was analyzed by electrophoretic mobility shift assay and reverse transcriptase-polymerase chain reaction in rat Rinm5F insulinoma cells. Preincubation with transport peptide-PNA-NFkappaB decoy (1 microM, 1 h) blocked IL-1beta-induced NFkappaB-binding activity and significantly reduced the IL-6 mRNA expression. The same concentration of NFkappaB decoy in the absence of transport peptide-PNA had no effect even after longer incubations. Our results showed that binding of the oligonucleotide NFkappaB decoy to the nonamer PNA sequence resulted in a stable complex that was efficiently translocated across the plasma membrane.

Animals↗

Testosterone regulates mRNA levels of calcium regulatory proteins in cardiac myocytes.

Gender-related differences in cardiac function have been described in the literature, but whether the presence of sex hormones is responsible for these differences remains unclear. This study was designed to determine whether testosterone regulates the gene expression of calcium regulatory proteins in rat heart, thus playing a role in gender-related differences in cardiac performance. Ventricular myocytes were isolated from two-day-old rats and treated with testosterone at varying duration; the levels of gene expression for the androgen receptor (AR) and major calcium regulatory proteins were determined by quantitative real-time PCR. Testosterone (1 microM) treatment induced a maximum increase in beta1-adrenergic receptor and L-type calcium channel mRNA levels following an eight hour exposure. Six hours testosterone treatment stimulated a 300-fold increase in androgen receptor message abundance, and Na/Ca exchanger mRNA levels reached a maximum level following twenty-four hour testosterone treatment. Taken together, these data provide the first evidence that testosterone regulates gene expression of the major calcium regulatory proteins in isolated ventricular myocytes, and may thus play a role in the gender-related differences observed in cardiac performance.

Androgens↗

ARIX gene polymorphisms in patients with congenital superior oblique muscle palsy.

AIM: To identify ARIX gene polymorphisms in patients with congenital superior oblique muscle palsy and to find the relation between the ARIX gene and congenital superior oblique muscle palsy. METHODS: The three exons of the ARIX gene were sequenced by genomic DNA amplification with polymerase chain reaction (PCR) and direct sequencing in 15 patients with superior oblique muscle palsy (13 with congenital and two with acquired palsy) and 54 normal individuals. PCR products cloned into plasmids were also sequenced. A family with father and a daughter each having congenital superior oblique muscle palsy was also involved in this study. RESULTS: Four patients with congenital superior oblique muscle palsy carried heterozygous nucleotide changes in the ARIX gene. One patient with the absence of the superior oblique muscle had T7C in the 5'-UTR of the exon 1 and C-44A in the promoter region, both of which were located on the same strand. Another unrelated patient with congenital superior oblique muscle palsy had C76G in the 5'-UTR of the exon 1 and C-9A in the promoter region on the same strand. G153A in the 5'-UTR of exon 1 was found in common in two affected members of a family with congenital superior oblique muscle palsy. This G153A in the 5'-UTR of exon 1 was also present in four unrelated normal individuals. No other heterozygous nucleotide changes were found in normal individuals. CONCLUSIONS: The nucleotide change (G153A) in the 5'-UTR of exon 1 co-segregated with congenital superior oblique muscle palsy in one family. Four other nucleotide changes in the exon 1 or the promoter region were found only in patients with congenital superior oblique muscle palsy. These nucleotide polymorphisms may be one of the risk factors for the development of congenital superior oblique muscle palsy.

Adult↗

Nuclear expression of Survivin in paediatric ependymomas and choroid plexus tumours correlates with morphologic tumour grade.

Survivin is a gene that is widely expressed throughout the development of the normal mammalian embryo. Subcellular localisation of Survivin to both the nucleus and cytoplasm has suggested multiple functional roles, including inhibition of cell death, especially as demonstrated within a variety of malignant cell types, as well as regulation of the mitotic spindle checkpoint. The expression of Survivin has been associated with an adverse clinical outcome in a large number of malignancies. However, nuclear Survivin expression has been described as an independent variable of favourable prognosis in two large clinical studies of breast and gastric carcinomas. Reports of Survivin expression in normal postnatal, differentiated tissues have been restricted to cell types with high proliferative capacities, including vascular endothelium, endometrium, colonic epithelium, and activated lymphocytes. Prior to this report, expression within the normal human brain had not been characterised. Here, we analyse the expression of Survivin in human brain sections obtained from perinatal and paediatric autopsy cases. We report a strikingly high level of expression of Survivin within normal ependyma and choroid plexus (CP). Analysis of corresponding neoplastic tissue in paediatric ependymomas and CP tumours shows that expression of the nuclear form of Survivin correlates with morphologic tumour grade, with a loss of nuclear expression associated with progressive cytologic anaplasia. This pattern of expression supports a hypothesis that Survivin plays a functional role in normal ependymal growth and/or neural stem cell differentiation, and that abnormally low levels of expression of the nuclear form of this protein may be a marker of more aggressive disease and/or higher morphologic grade in ependymal and CP tumours.

Adolescent↗

HMW and LMW glutenin alleles among putative tetraploid and hexaploid European spelt wheat (Triticum spelta L.) progenitors.

The allelic compositions of high- and low-molecular-weight subunits of glutenins (HMW-GS and LMW-GS) among European spelt ( Triticum spelta L.) and related hexaploid and tetraploid Triticum species were investigated by one- and two-dimensional polyacrylamide-gel electrophoresis (PAGE) and capillary electrophoresis (CE). A total of seven novel glutenin alleles (designated A1a*, B1d*, B1g*, B1f*, B1j*, D1a* at Glu-1 and A3h at the Glu-3 loci, respectively) in European spelt wheat were detected by SDS-PAGE, which were confirmed further by employing A-PAGE and CE methods. Particularly, two HMW-GS alleles, Glu-B1d* coding the subunits 6.1 and 22.1, and Glu-B1f* coding the subunits 13 and 22*, were found to occur in European spelt with frequencies of 32.34% and 5.11%, respectively. These two alleles were present in cultivated emmer (Triticum dicoccum), but they were not observed in bread wheat (Triticum aestivum L.). The allele Glu-B1g* coding for 13* and 19* subunits found in spelt wheat was also detected in club wheat (Triticum compactum L.). Additionally, two alleles coding for LMW-GS, Glu-A3h and Glu-B3d, occurred with high frequencies in spelt, club and cultivated emmer wheat, whereas these were not found or present with very low frequencies in bread wheat. Our results strongly support the secondary origin hypothesis, namely European spelt wheat originated from hybridization between cultivated emmer and club wheat. This is also confirmed experimentally by the artificial synthesis of spelt through crossing between old European emmer wheat, T. dicoccum and club wheat, T. compactum.

Alleles↗

Simultaneous determination of N-butyramide-tacrine and tacrine in mouse plasma and brain homogenate by high-performance liquid chromatography with a simple gradient solvent system.

A novel reversed-phase HPLC method was developed for the simultaneous determination of tacrine (THA) and the newly synthesized prodrug (N-butyramide-THA, BTHA) in mouse plasma and brain homogenate. The assay involves deproteinisation and subsequent detection at 240 nm with a gradient solvent system. Retention times were 18.5 and 9.3 min for BTHA and THA, respectively. Average recoveries for the analytes were 80.7% (BTHA) and 76.6% (THA) from plasma, and 75.0% (BTHA) and 68.4% (THA) from brain homogenate. Linear responses were observed over a wide range (0.25-20 microg/ml for BTHA in plasma and in brain homogenate, 0.025-20 microg/ml for THA in both matrices). Both BTHA and THA degraded from the prodrug can be detected even 12 h after intravenous administration of BTHA, indicating that BTHA is a promising prodrug for brain targeting.

Animals↗

Thrombin preconditioning upregulates transferrin and transferrin receptor and reduces brain edema induced by lysed red blood cells.

Pretreatment with a low dose of thrombin reduces brain edema after both hemorrhagic and ischemic stroke. We call this phenomenon thrombin preconditioning (TPC) or thrombin-induced brain tolerance. The present study examines whether TPC can attenuate the brain edema induced by lysed red blood cells (RBCs) to determine whether thrombin production early in an intracerebral hemorrhage (ICH) might alter potentially injurious events associated with clot resolution. It also examines whether TPC might be protective by altering iron handling within the brain, particularly through modulating transferrin (Tf) and transferrin receptor (TfR) levels. Brain edema was measured by wet/dry weight. Western blot analysis and immunohistochemistry were used for Tf and TfR measurements. We found that TPC reduces lysed RBC-induced brain edema and upregulates both Tf and TfR levels in the brain. Thrombin formation after an ICH may be part of a signaling cascade that acts to limit potentially injurious events associated with clot resolution through altering iron-handling proteins.

Animals↗

Influence of Th1, Th2, and Th3 cytokines during the early phase after liver transplantation.

To investigate the change of Th1, Th2, Th3 cytokines during early liver transplantation. IFN-r, IL-4, TGF-beta production by CD4+ T cells were determined by fluorescence activated cell sorter analysis. Comparing the acute rejection with the non-acute rejection groups on the 7th, 14th, and 28th day showed that high interferon-gamma production associated with acute rejection in the early posttransplant period. There was no evidence of significant changes in interleukin-4 and transforming growth factor beta (TGF-beta) levels between non-acute rejection groups with acute rejection groups. Th1 cytokine high production is significantly associated with acute rejection in liver transplant recipients.

CD4-CD8 Ratio↗