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Biomedical subjects

Y Ji

Publications and source records attributed to Y Ji.

At least 19 recordsLinked to original sources

Chronic prenatal ethanol exposure increases apoptosis in the hippocampus of the term fetal guinea pig.

It is hypothesized that chronic prenatal ethanol exposure (CPEE), via maternal ethanol administration, increases mitochondrial-directed apoptosis in the hippocampus of the term fetus that precedes loss of hippocampal CA1 pyramidal cells. To test this hypothesis, timed pregnant guinea pigs received chronic oral administration of: 4 g ethanol/kg maternal body weight/day, isocaloric-sucrose/pair-feeding or water throughout gestation. At gestational day 65 (term fetus) and postnatal day 0 (neonate), individual offspring were euthanized, and the brain was excised and dissected. CPEE, compared with the isocaloric-sucrose/pair-fed and water control groups, decreased the brain weight of the term fetus and neonate. CPEE did not alter the density of CA1 pyramidal cells in the hippocampus of the term fetus and neonate. In the term fetus, CPEE increased cytochrome c content in the cytosolic fraction of the hippocampus, altered the mitochondrial localization of cytochrome c in cells of the dorsal hippocampus, and increased the percentage of cells in the dorsal hippocampus containing activated caspase-3 and cleaved poly(ADP-ribose) polymerase. The data indicate that CPEE increases neuroapoptosis in the hippocampus of term fetus, which appears to occur via an intrinsic, mitochondrial-directed mechanism initiated by leakage of pro-apoptotic cytochrome c from mitochondria into the cytoplasm.

Animals↗

Charge and charging compensation on oxides and hydroxides in oxygen environmental SEM.

Oxygen environment was applied to the scanning electron microscopy (SEM) analysis of insulating samples. In the high vacuum SEM, a local oxygen pressure was provided, and in the environmental SEM, oxygen atmosphere was used instead of water, the commercial mode. The charging effects in the SEM observation and component characterization of samples such as Al(2)O(3), Al(OH)(3), Mg(OH)(2) and others can be eliminated or significantly reduced. The oxygen environment does not only provide a new approach to releasing the charging difficulty in the analyses using electron beam as a probe, but also provide an insightful hint to the understanding of the charging processes in general.

Journal Article↗

Menin molecular interactions: insights into normal functions and tumorigenesis.

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disease predisposed by heterozygous germline mutations in the MEN1 tumor suppressor gene. Biallelic loss of MEN1 resulting from small mutation and/or loss of heterozygosity occurs in a large tissue spectrum of MEN1 tumors or non-hereditary tumors. Mouse models of MEN1 underexpression or overexpression have also supported the tumor-suppressor effect of the MEN1 gene. Menin, the 610-amino-acid protein encoded by MEN1, is expressed ubiquitously and found predominantly in the nucleus. Sequence analyses do not reveal motifs of known function other than two nuclear localization sequences. Menin has been found to partner in vitro with a variety of proteins that comprise transcription factors, DNA processing factors, DNA repair proteins, and cytoskeletal proteins. The diverse functions of menin interactors suggest roles for menin in multiple biological pathways. Inactivation of menin switches its JunD partner from a downstream action of growth suppression to growth promotion. This is a plausible mechanism for menin tumorigenesis.

Animals↗

Identification of a novel HLA-A*0278 allele in a Chinese family.

A novel human leukocyte antigen-A (HLA-A) allele, A*0278, has been identified in a Chinese family using DNA-based typing and molecular cloning methods. The alleles A*0278 differs from its closest matching HLA sequence of A*0256 by a silent substitution at 102 A > C and by two replacement substitutions, 98T > A and 292 C > G in exon 2, resulting in a change of codon 33 from Phe (TTC) to Tyr (TAC) and codon 98 from His (CAC) to Asp (GAC). Serology study revealed that A*0278 is associated with HLA-A2 broad specificity. A polymerase chain reaction-sequence-specific primers-based assay was developed to identify A*0278. Family study indicated that the propositus inhered his father's HLA haplotype A*0278, B*35, DRB1*15. No further individuals of A*0278 were found in 5000 Chinese bone marrow donor volunteers.

Alleles↗

Current-driven switching in a single exchange-biased ferromagnetic layer.

We demonstrate spin-transfer torque effects in a single exchange-biased ferromagnetic layer. A current through a point contact to the exchange-biased Co layer reverses the magnetization of a nanodomain in the layer hysteretically for low applied magnetic fields and reversibly for high fields (up to 9 T). These effects are the inverse of the domain wall magnetoresistance, in the same way that similar effects in multilayers are the inverse of giant magnetoresistance.

Journal Article↗

Study on the haplotypes of MICA and MICB microsatellite and HLA-B locus in the Guangzhou Han population.

The purpose of this study was to investigate the genetic polymorphisms and haplotypes of microsatellite locus in exon 5 of the MICA gene and intron 1 of the MICB gene and human leukocyte antigen-B (HLA-B) gene based on 106 samples of the Guangzhou Han population through means of polymerase chain reaction and the fluorescent technique (6-FAM). The corresponding haplotype frequencies, linkage disequilibrium values and relative linkage disequilibrium values were estimated based on population data. The results show that the genotype distributions of MICA and MICB microsatellite and HLA-B satisfy the Hardy-Weinberg equilibrium. In total, five alleles of MICA microsatellite locus and 14 alleles of MICB microsatellite locus were observed. MICA A5 was the most common allele (0.2877), whereas A4 was the least common (0.1321). MICB CA14 was the most common allele (0.3255), and CA19 and CA28 were the two least common (0.0047). CA27 was not observed at all. Five kinds of MICA-MICB haplotypes, 18 kinds of MICA-HLA-B haplotypes and 12 kinds of MICB-HLA-B haplotypes occurred at frequencies of more than 1%. The common haplotypes of MICA-MICB, MICA-HLA-B and MICB-HLA-B were A5-CA14, A5.1-CA18, A4-CA26, A9-CA15, A5-B*15(62), A5.1-B*1301/1302, A4-B*1301/1302, A6-B*51, A6-B*4403, A9-B*3802, CA14-B*4601, CA18-B*1301/1302 and CA26-B*1301/1302, and these haplotypes showed strong linkage disequilibrium. The polymorphisms and haplotype distributions of MICA and MICB microsatellite and HLA-B locus in the Guangzhou Han population have their own distinct genetic characteristics. The microsatellite locus of exon 5 of the MICA gene and intron 1 of the MICB gene could therefore be used as genetic markers in the studies of anthropology, gene linkage analysis in genetic diseases, individual identification and paternity testing in forensic medicine.

Asian People↗

Nitric oxide generation mediated by beta-adrenoceptors is impaired in platelets from patients with Type 2 diabetes mellitus.

AIMS/HYPOTHESIS: Type 2 diabetic patients have been shown to have reduced basal platelet nitric oxide synthase activity, which is a possible contributor to the vascular complications seen in the disease. We investigated platelet nitric oxide generation stimulated by beta-adrenoceptors and adenylyl cyclase in Type 2 diabetic patients and control subjects. METHODS: Platelets isolated from blood taken from nine Type 2 diabetic patients and nine healthy control subjects of similar age were treated with isoproterenol 1 micro mol/l, forskolin 1 micro mol/l or vehicle. Platelet nitric oxide synthase activity was measured by L-[(3)H]-arginine to L-[(3)H]-citrulline conversion, cyclic GMP content by radioimmunoassay, and nitric oxide synthase type 3 expression by western blotting. RESULTS: Basal platelet nitric oxide synthase activity was lower in diabetic patients than in control subjects (0.01+/-0.02 pmol L-citrulline/10(8) platelets, compared with 0.12+/-0.05; p<0.05), although no corresponding difference was seen in basal platelet cyclic GMP (0.61+/-0.39 and 0.13+/-0.22 pmol cyclic GMP/10(8) platelets respectively; p=0.37). In control subjects isoproterenol 1 micro mol/l and forskolin 1 micro mol/l increased platelet nitric oxide synthase activity (to 0.27+/-0.08 and 0.27+/-0.07 pmol L-citrulline/10(8) platelets respectively; p<0.05 for each in comparison with basal) and cyclic GMP (to 1.84+/-0.41 and 1.86+/-0.48; p<0.05 for each in comparison with basal). This effect was not achieved in diabetic patients. Isoproterenol- and forskolin-stimulated cyclic GMP correlated inversely with plasma glucose and HbA(1c). Platelet nitric oxide synthase type 3 expression was not different in control and diabetic subjects and was not changed by acute exposure of platelets to isoproterenol. CONCLUSIONS/INTERPRETATION: Nitric oxide generation stimulated by beta-adrenoceptors and adenylyl cyclase is impaired in platelets of people with Type 2 diabetes mellitus, with no corresponding change in nitric oxide synthase type 3 expression. It is possible that this impairment contributes to the thrombotic and atherosclerotic complications of Type 2 diabetes.

Angiotensin-Converting Enzyme Inhibitors↗

Current-induced spin-wave excitations in a single ferromagnetic layer.

Evidence for a current-induced spin-transfer torque effect has been investigated in a series of point contacts to single ferromagnetic layers. At specific current densities, abrupt resistance changes, similar to those attributed to current-induced spin-wave excitations in multilayers, have been observed for one current polarity. The critical current for these resistance changes depends linearly on the external field applied perpendicular to the layer. The observed effect is interpreted as a current-driven heterogeneous instability in an otherwise uniform ferromagnetic layer.

Journal Article↗

Homoeologous pairing and recombination in Solanum lycopersicoides monosomic addition and substitution lines of tomato.

We compared meiotic pairing and recombination between tomato ( Lycopersicon esculentum) and homoeologous Solanum lycopersicoides chromosomes in monosomic additions (MAs) and substitution lines (SLs), each representing a single chromosome of the nightshade in a tomato background. Three configurations of each alien chromosome and its two tomato homoeologues were detected by genomic in situ hybridization in MA-7, -8, and -10 at diakinesis/metaphase-I: 1 trivalent (III), 1 bivalent + 1 univalent (II+I), and 3 univalents (3I). The II+I category was by far the most common, and the univalent was from S. lycopersicoides 91-99.5% of the time, indicating a high degree of preferential (homologous) pairing. In the corresponding substitution lines, association of homoeologous chromosomes was much higher (up to 90% of the cells), presumably due to the absence of homologous partners. However, SL-10 showed a surprisingly high frequency of univalents (about 73%). Genome-wide analysis of chromosome pairing revealed a decrease in the average chiasma frequency for both monosomic additions and substitution lines. Recombination between tomato and the nightshade was restricted in all cases, the reduction being more severe in each monosomic addition than in the corresponding substitution line. Recombination rates in the substitutions were less than those observed for the same chromosomes in the first backcross generation. Chromosomes 8 and 10 showed the highest and the lowest rates of homoeologous recombination, respectively. No recombination was detected between markers on the long arm of chromosome 10, presumably due to the presence of a paracentric inversion differentiating the two genomes in this region. The frequency of homoeologous pairing at diakinesis/metaphase-I was significantly higher than the rate of homoeologous recombination detected in the progeny, suggesting a strong selection against recombinant products in meiotic or post-meiotic stages.

Chromosome Mapping↗

Apolipoprotein E isoform-specific regulation of dendritic spine morphology in apolipoprotein E transgenic mice and Alzheimer's disease patients.

Dendritic spines are postsynaptic sites of excitatory input in the mammalian nervous system. Apolipoprotein (apo) E participates in the transport of plasma lipids and in the redistribution of lipids among cells. A role for apoE is implicated in regeneration of synaptic circuitry after neural injury. The apoE4 allele is a major risk factor for late-onset familial and sporadic Alzheimer's disease (AD) and is associated with a poor outcome after brain injury. ApoE isoforms are suggested to have differential effects on neuronal repair mechanisms. In vitro studies have demonstrated the neurotrophic properties of apoE3 on neurite outgrowth. We have investigated the influence of apoE genotype on neuronal cell dendritic spine density in mice and in human postmortem tissue. In order to compare the morphology of neurons developing under different apoE conditions, gene gun labeling studies of dendritic spines of dentate gyrus (DG) granule cells of the hippocampus were carried out in wild-type (WT), human apoE3, human apoE4 expressing transgenic mice and apoE knockout (KO) mice; the same dendritic spine parameters were also assessed in human postmortem DG from individuals with and without the apoE4 gene. Quantitative analysis of dendritic spine length, morphology, and number was carried out on these mice at 3 weeks, 1 and 2 years of age. Human apoE3 and WT mice had a higher density of dendritic spines than human E4 and apoE KO mice in the 1 and 2 year age groups (P<0.0001), while at 3 weeks there were no differences between the groups. These age dependent differences in the effects of apoE isoforms on neuronal integrity may relate to the increased risk of dementia in aged individuals with the apoE4 allele. Significantly in human brain, apoE4 dose correlated inversely with dendritic spine density of DG neurons cell in the hippocampus of both AD (P=0.0008) and aged normal controls (P=0.0015). Our findings provide one potential explanation for the increased cognitive decline seen in aged and AD patients expressing apoE4.

Aged↗

NMDA receptor antagonists attenuate noxious and nonnoxious colorectal distention-induced Fos expression in the spinal cord and the visceromotor reflex.

In the present three-part study, the effects of intrathecally administered N-methyl-D-aspartate (NMDA) receptor antagonists on responses to noxious and innocuous colorectal distention (CRD) were examined. In the first part, a passive-avoidance paradigm was used to confirm that 80 mm Hg CRD is a noxious stimulus since it produced avoidance behavior. Acquisition of this behavior was blocked by the NMDA receptor antagonist D(-)-2-amino-5-phosphonopetanoic acid (APV, 60 nmol, intrathecal). In contrast, 20 mm Hg CRD is an innocuous stimulus since there was no difference in the behavior of these animals compared to nondistended controls. In the second part, the effects of the NMDA receptor antagonist dizocilpine maleate (MK-801, 0-100 nmol, intrathecal) on CRD-induced Fos expression in the lumbosacral spinal cord were examined. Noxious and innocuous CRD induced 98+/-4 and 50+/-2 Fos labeled cells per section per side of the spinal cord, respectively. MK-801 dose-dependently attenuated noxious CRD-induced Fos. Compared to saline, the peak attenuation was 55%. Innocuous CRD-induced Fos was attenuated by 36% following 100 nmol MK-801. In the third part, the effects of APV (0-240 nmol, intrathecal) on the visceromotor reflex were examined. APV dose-dependently attenuated the visceromotor reflex to graded intensities of CRD that went from the innocuous into the noxious range. In separate animals that only received innocuous stimulation, APV dose-dependently attenuated the visceromotor reflex. The magnitude of attenuation was similar for both stimulus paradigms. These data expand upon our previous dorsal horn neuronal recordings which showed that spinal NMDA receptors partially mediate the processing of both noxious and innocuous colorectal stimuli. They further underscore a difference from somatic tissue in the role of NMDA receptors in processing acute or transient visceral stimuli in the absence of tissue injury.

2-Amino-5-phosphonovalerate↗

Therapeutic effects of astrocytes expressing both tyrosine hydroxylase and brain-derived neurotrophic factor on a rat model of Parkinson's disease.

Tyrosine hydroxylase (TH) and brain-derived neurotrophic factor (BDNF), expressed in normal astrocytes, were used in combination for the treatment of Parkinson's disease (PD) symptoms in a rat model. Normal neonatal rat astrocytes were co-transfected with a vector expressing BDNF (AAVBDNF) and a retroviral vector expressing TH (termed TH-BDNF-DA(+) cells), and then implanted into the striatum of PD rats induced by 6-hydroxydopamine. TH-BDNF-DA(+) cells compensated for a severe insufficiency of endogenous dopaminergic neurons in the PD rats, resulting in a significant improvement of PD symptoms. The decrease in the rotational rate of PD rats implanted with TH-BDNF-DA(+) cells was more marked than that in PD rats implanted with normal astrocytes expressing either TH or BDNF alone (termed TH(+) and BDNF(+) cells, P<0.01 and 0.001, respectively), and suggested a synergistic effect between TH and BDNF. In contrast, the rotational rate was not altered from the baseline in PD rats without treatment or implanted with parental rat astrocytes alone (P>0.05). BDNF protected the dopaminergic neurons from apoptosis induced by 6-hydroxydopamine, and significantly increased the long-term survival of TH-positive cells in the striatum. Our data indicate that the combined use of TH and BDNF has a synergistic therapeutic effect, and is more efficient for the treatment of PD than a single gene therapy using either TH or BDNF alone.

Animals↗

Enterovirus replication in valvular tissue from patients with chronic rheumatic heart disease.

AIMS: To investigate the involvement of enterovirus infection in chronic, rheumatic heart disease. METHODS AND RESULTS: Formalin-fixed, paraffin-embedded, surgical samples of valve tissue were examined for the presence of enteroviral RNA and virus capsid protein VP1 by in situ hybridization and immunostaining. Of 53 cases, 33 were patients with chronic rheumatic heart disease and 20 had Marfan's syndrome or degenerative valve disease. Enterovirus RNA was detected in 8 (24.2%) of 33 patients with chronic rheumatic heart disease by in situ hybridization using strand-specific oligonucleotide probes, complementary to conserved sequences in enterovirus genomic (positive strand) RNA. The replication template (negative strand) RNA also was found in seven of these eight cases. The viral capsid protein VP1 was detected in 16 (48.5%) of 33 patients with chronic rheumatic heart disease by immunohistochemistry and correlated with viral RNA detection. Virus was localized generally to valvular tissue. Neither viral RNA nor capsid protein VP1 were found in valvular tissue from any of the 20 comparison cases. CONCLUSIONS: This is the first demonstration of detection and localization of both enterovirus RNA and capsid protein in chronic rheumatic heart disease. The presence of negative strand RNA and VP1 indicates enteroviral RNA replication and protein synthesis and suggests an aetiological role of enterovirus in the pathogenesis of chronic rheumatic heart disease.

Adult↗

Identification of critical staphylococcal genes using conditional phenotypes generated by antisense RNA.

Comprehensive genomic analysis of the important human pathogen Staphylococcus aureus was achieved by a strategy involving antisense technology in a regulatable gene expression system. In addition to known essential genes, many genes of unknown or poorly defined biological function were identified. This methodology allowed gene function to be characterized in a comprehensive, defined set of conditionally growth-defective/lethal isogenic strains. Quantitative titration of the conditional growth effect was performed either in bacterial culture or in an animal model of infection. This genomic strategy offers an approach to the identification of staphylococcal gene products that could serve as targets for antibiotic discovery.

Animals↗

Molecular identification and sequence analysis of Hillarin, a novel protein localized at the axon hillock.

The monoclonal antibody Lan3-15 identifies a novel protein, Hillarin, that is localized to the axon hillock of leech neurons. Using this antibody we have identified a full length cDNA coding for leech Hillarin and determined its sequence. The gene encodes a 1274 residue protein with a predicted molecular mass of 144013 Da. Data base searches revealed that leech Hillarin has potential orthologues in fly and nematode and that these proteins share two novel protein domains. The W180 domain is characterized by five conserved tryptophans whereas the H domains share 21 invariant residues. In contrast to the arrangement in fly and nematode the cassette containing the W180 and H domains is repeated twice in leech Hillarin. This suggests that the leech Hillarin sequence originated from a duplication event of an ancestral protein with single cassette structure.

Amino Acid Sequence↗