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Biomedical subjects

X Yu

Publications and source records attributed to X Yu.

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

Functional phenotype in transgenic mice expressing mutant human presenilin-1.

Mutations in the presenilin-1 (PS1) gene cause approximately 50% of cases of early onset familial Alzheimer's disease. The function of this protein remains unknown. We have made an electrophysiological study of hippocampal slices from transgenic mice expressing either a normal human PS1 transgene (WT) or one of two human PS1 transgenes bearing pathogenic mutations at codon M146 (M146L and M146V). Medium and late afterhyperpolarizations in CA3 pyramidal cells were larger in mice expressing either mutant form compared with WT and nontransgenic controls. Calcium responses to depolarization were larger in M146L mice compared with nontransgenic littermates; synaptic potentiation of the CA3 to CA1 projection was also stronger. These results demonstrate disruption of the control of intracellular calcium and electrophysiological dysfunction in PS1 mutant mice.

Alzheimer Disease↗
PubMed2000

Characterization of pathology in transgenic mice over-expressing human genomic and cDNA tau transgenes.

To examine the normal cellular function of tau and its role in pathogenesis, we have created transgenic mice that overexpress a tau transgene derived from a human PAC that contains the coding sequence, intronic regions, and regulatory regions of the human gene. All six isoforms of human tau are represented in the transgenic mouse brain at the mRNA and protein level and the human tau is distributed in neurites and at synapses, but is absent from cell bodies. A comparison between the genomic tau mice and mice that overexpress a tau cDNA transgene shows that overall, the distribution of tau is similar in the two lines, but human tau is located in the somatodendritic compartment of many neurons in the cDNA mice. Tau-immunoreactive axonal swellings were found in the spinal cords of the cDNA mice, which correlated with a hind-limb abnormality, whereas neuropathology was essentially normal in the genomic mice up to 8 months of age.

Alzheimer Disease↗
PubMed2000

Functionally heterogeneous segmental oscillators generate swimming in the medical leech.

Swimming behavior in the leech Hirudo medicinalis arises from neuronal circuits within the ventral nerve cord. Although the ventral nerve cord comprises a series of homologous segmental ganglia, it remains unresolved whether the swim oscillator circuits within individual ganglia are functionally equivalent. We have extended previous studies on pairs of ganglia to test whether individual ganglia throughout the nerve cord are capable of generating swim oscillations and to measure the cycle periods of local oscillations. We found that the swim-generating function of individual ganglia is broadly distributed, but not uniform. The swim-like oscillations in isolated ganglia from the anterior ganglia nerve cord were less robust than those from mid-cord. Swimming activity in posterior cord ganglia is even weaker we were unable to obtain swim-like oscillations from individual ganglia of the nerve cord posterior to segment 12. Swim-cycle periods exhibited a U-shaped function: those recorded in the most anterior individual ganglia (2.3 s for ganglion M2) and short chains of posterior ganglia (up to 4.0 s) were two to four times longer than those obtained from mid-cord ganglia (near 1.0 s). We conclude that the leech swim system comprises a functionally heterogeneous set of local oscillator units.

Animals↗
PubMed2000

Dynamic process of information transmission complexity in human brains.

Based on a complexity analysis of mutual information transmission of EEG developed by us [Xu J, Liu Z, Liu R, Yang Q (1997) Physica D 106: 363-374], dynamic processes of the complexity of mutual information transmission in human brains were studied. To diminish possible problems due to coarse graining preprocessing, some new measures of complexity were used. The results show that, just before and after generalized seizures, the complexities of almost all information transmission between different brain areas drop significantly; there is also a temporary decrease of complexity when subjects shift their attention. The above facts suggest that there is a transient decrease of information transmission complexity when brain state changes occur suddenly. Mental arithmetic tasks activate the left temporal lobe to exchange more information with other brain areas. The results hint that the methods used here might be an approach to observe quick processes in the living brain.

Adult↗
PubMed2000

BCL-6 represses genes that function in lymphocyte differentiation, inflammation, and cell cycle control.

BCL-6, a transcriptional repressor frequently translocated in lymphomas, regulates germinal center B cell differentiation and inflammation. DNA microarray screening identified genes repressed by BCL-6, including many lymphocyte activation genes, suggesting that BCL-6 modulates B cell receptor signals. BCL-6 repression of two chemokine genes, MIP-1alpha and IP-10, may also attenuate inflammatory responses. Blimp-1, another BCL-6 target, is important for plasmacytic differentiation. Since BCL-6 expression is silenced in plasma cells, repression of blimp-1 by BCL-6 may control plasmacytic differentiation. Indeed, inhibition of BCL-6 function initiated changes indicative of plasmacytic differentiation, including decreased expression of c-Myc and increased expression of the cell cycle inhibitor p27kip1. These data suggest that malignant transformation by BCL-6 involves inhibition of differentiation and enhanced proliferation.

Animals↗
PubMed2000

Neurofibrillary tangles, amyotrophy and progressive motor disturbance in mice expressing mutant (P301L) tau protein.

Neurofibrillary tangles (NFT) composed of the microtubule-associated protein tau are prominent in Alzheimer disease (AD), Pick disease, progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). Mutations in the gene (Mtapt) encoding tau protein cause frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17), thereby proving that tau dysfunction can directly result in neurodegeneration. Expression of human tau containing the most common FTDP-17 mutation (P301L) results in motor and behavioural deficits in transgenic mice, with age- and gene-dose-dependent development of NFT. This phenotype occurred as early as 6.5 months in hemizygous and 4.5 months in homozygous animals. NFT and Pick-body-like neuronal lesions occurred in the amygdala, septal nuclei, pre-optic nuclei, hypothalamus, midbrain, pons, medulla, deep cerebellar nuclei and spinal cord, with tau-immunoreactive pre-tangles in the cortex, hippocampus and basal ganglia. Areas with the most NFT had reactive gliosis. Spinal cord had axonal spheroids, anterior horn cell loss and axonal degeneration in anterior spinal roots. We also saw peripheral neuropathy and skeletal muscle with neurogenic atrophy. Brain and spinal cord contained insoluble tau that co-migrated with insoluble tau from AD and FTDP-17 brains. The phenotype of mice expressing P301L mutant tau mimics features of human tauopathies and provides a model for investigating the pathogenesis of diseases with NFT.

Amino Acid Substitution↗
PubMed2000

Regulation of AMPA receptor endocytosis by a signaling mechanism shared with LTD.

The endocytosis of AMPA receptors is thought to be important in the expression of long-term depression (LTD) triggered by NMDA receptor activation. Although signaling pathways necessary for LTD induction have been identified, those responsible for the regulated internalization of AMPA receptors are unknown. Here we show that activation of NMDA receptors alone can trigger AMPA receptor endocytosis through calcium influx and activation of the calcium-dependent protein phosphatase calcineurin. A distinct signaling mechanism mediates the AMPA receptor endocytosis stimulated by insulin. These results demonstrate that although multiple signaling pathways can induce AMPA receptor internalization, NMDA receptor activation enhances AMPA receptor endocytosis via a signaling mechanism required for the induction of LTD.

Animals↗
PubMed2000

Reproductive toxicity of 1-bromopropane, a newly introduced alternative to ozone layer depleting solvents, in male rats.

1-Bromopropane has been newly introduced as an alternative to ozone-depleting solvents. We aimed to clarify its dose-dependent reproductive toxicity in male rats. Thirty-six Wistar male rats were randomly divided into 4 groups of 9. The groups were exposed to 200, 400, or 800 ppm 1-bromopropane or only fresh air, 8 h per day for 12 weeks. Epididymal sperm indices were evaluated after a 12-week exposure. The testes, epididymides, seminal vesicle, prostate, and other organs were weighed and examined histopathologically. Spermatogenic cells, in stage VII seminiferous tubules, and retained spermatids, at the basal region of stages IX-XI seminiferous epithelium, were counted. Plasma testosterone levels were measured by radioimmunoassay. The testicular weight did not significantly change, but the weight of epididymides, seminal vesicle, and prostate dose-dependently decreased. The weight of seminal vesicle decreased significantly at the lowest concentration of 200-ppm and over. 1-Bromopropane induced a dose-dependent decrease in the epididymal sperm count and in motility, as well as an increase in tailless sperm and sperm with an immature head shape. The spermatogonia, preleptotene spermatocytes, pachytene spermatocytes, and round spermatids did not decrease significantly at stage VII. Retained, elongated spermatids near the basement membrane at the postspermiation stages IX-XI increased dose-dependently. Plasma testosterone levels significantly decreased at the 800-ppm dosage. 1-Bromopropane caused failure of spermiation. Its reproductive toxicity is different from that of 2-bromopropane, which specifically impairs spermatogonia. Thus, this solvent may have serious reproductive toxic effects in men, and should be used very cautiously in the workplace.

Administration, Inhalation↗
PubMed2000

1-Bromopropane, an alternative to ozone layer depleting solvents, is dose-dependently neurotoxic to rats in long-term inhalation exposure.

1-Bromopropane has been newly introduced as an alternative to ozone layer-depleting solvents. We aimed to clarify the dose-dependent effects of 1-bromopropane on the nervous system. Forty-four Wistar male rats were randomly divided into 4 groups of 11 each. The groups were exposed to 200, 400, or 800 ppm of 1-bromopropane or only fresh air 8 h per day for 12 weeks. Grip strength of forelimbs and hind limbs, maximum motor nerve conduction velocity (MCV), and distal latency (DL) of the tail nerve were measured in 9 rats of each group every 4 weeks. The other 2 rats of each group were perfused at the end of the experiment for morphological examinations. The rats of the 800-ppm group showed poor kicking and were not able to stand still on the slope. After a 12-week exposure, forelimb grip strength decreased significantly at 800 ppm and hind limb grip strength decreased significantly at both 400 and 800 ppm or after a 12-week exposure. MCV and DL of the tail nerve deteriorated significantly at 800 ppm. Ovoid or bubble-like debris of myelin sheaths was prominent in the unraveled muscular branch of the posterior tibial nerve in the 800-ppm group. Swelling of preterminal axons in the gracile nucleus increased in a dose-dependent manner. Plasma creatine phosphokinase (CPK) decreased dose-dependently with significant changes at 400 and 800 ppm. 1-Bromopropane induced weakness in the muscle strength of rat limbs and deterioration of MCV and DL in a dose-dependent manner, with morphological changes in peripheral nerve and preterminal axon in the gracile nucleus. 1-Bromopropane may be seriously neurotoxic to humans and should thus be used carefully in the workplace.

Administration, Inhalation↗
PubMed2000

Enhanced transgene expression and effective in vivo antitumor immune responses initiated by dendritic progenitors transfected with a nonviral T7 vector expressing a model tumor antigen.

Genetic education of dendritic cells (DCs) with tumor-associated antigens is an encouraging development in DC-mediated tumor immunotherapy. In this study, to increase the transgene expression by DCs using nonviral vectors, a cytoplasmic T7 vector (T7T7/T7Luc) was used to transfect bone marrow-derived DCs with the firefly luciferase gene as a reporter and as a model tumor antigen. As a result, the luciferase activity of T7T7/T7Luc-transfected DCs was more than four times greater than that of DCs transfected with pCMVLuc, a commonly used nonviral vector. Furthermore, the luciferase activity was increased three times more when dendritic progenitor cells rather than mature DCs were transfected. In vivo tumor studies showed that T7T7/T7Luc-transfected DCs, which express high levels of luciferase (model tumor antigen), stimulated a stronger immune response than did pCMVLuc-transfected DCs, which express relatively low levels of luciferase, as indicated by the cytotoxic T lymphocyte assay. T7T7/T7Luc transfected DCs, when injected into recipient mice, evoked an antigen-specific immune response that can effectively eradicate implanted metastasis and prevent new tumor development by murine melanoma cells genetically modified to express luciferase. Therefore, the T7 system is a powerful nonviral vector that can be used to genetically educate DCs with tumor-associated antigens for tumor immunotherapy.

Animals↗
PubMed2000

Three-dimensional structure of the human herpesvirus 8 capsid.

Human herpesvirus 8 (HHV-8), or Kaposi's sarcoma-associated herpesvirus, is a gammaherpesvirus implicated in all forms of Kaposi's sarcoma and certain lymphomas. HHV-8 has been extensively characterized, both biochemically and immunologically, since its first description in 1994. However, its three-dimensional (3D) structure remained heretofore undetermined largely due to difficulties in viral purification. We have used log-phase cultures of body cavity-based lymphoma 1 cells induced with 12-O-tetradecanoylphorbol-13-acetate to obtain HHV-8 capsids for electron cryomicroscopy and computer reconstruction. The 3D structure of the HHV-8 capsids revealed a capsid shell composed of 12 pentons, 150 hexons, and 320 triplexes arranged on a T=16 icosahedral lattice. This structure is similar to those of herpes simplex virus type 1 (HSV-1) and human cytomegalovirus (HCMV), which are prototypical members of alpha- and betaherpesviruses, respectively. The inner radius of the HHV-8 capsid is identical to that of the HSV-1 capsid but is smaller than that of the HCMV capsid, which is consistent with the relative sizes of the genomes they enclose. While the HHV-8 capsid exhibits many structural similarities to the HSV-1 capsid, our reconstruction shows two major differences: its hexons lack the "horn-shaped" VP26 densities bound to the HSV-1 hexon subunits, and the HHV-8 triplexes appear smaller and less elongated than those of HSV-1. These differences are in excellent agreement with our sequence comparisons of HHV-8 and HSV-1 capsid proteins. This gammaherpesvirus capsid structure complements previous structural studies on alpha- and betaherpesviruses in providing an account of structural similarities and differences among capsids representing all human herpesvirus subfamilies.

Capsid↗
PubMed2000

Stereotactic biopsy for intracranial space-occupying lesions: clinical analysis of 550 cases.

OBJECT: To investigate the role of stereotactic biopsy in planning the optimal management of intracranial space-occupying lesions. PATIENTS AND METHODS: Between December 1989 and December 1999, stereotactic biopsy was performed in 550 patients with intracranial mass lesions that were deep-seated or located in the functional area. There were 340 males and 210 females, and their ages ranged from 4 to 75 years. All the procedures were done under local anesthesia with a Leksell stereotactic system. A CT scan was used to determine the coordinates in the first 420 cases and the Aero Tech Stereotactic Surgical Plan System in the subsequent 130 patients. RESULTS: Brain tumors were diagnosed pathologically in 475 patients (86.4%), inflammatory process in 44 (8.0%), other lesions in 12 (2.2%) and no conclusive diagnosis was found in 19 (3.4%). The overall positive rate of biopsy was 96.6%, and the positive rate for brain tumor was 86.4%. Intracranial hematomas after biopsy were found in 13 cases (2.4%). Seizures occurred during the operation in 7 cases (1.2%), and slight and transient neurological deficits were found in 23 cases (4.2%). There were no deaths or other serious complications. CONCLUSIONS: The results suggest that the stereotactic biopsy is a reliable method to obtain histopathological diagnosis of intracranial mass lesions, and it is also of great help in selecting the appropriate management.

Adolescent↗
PubMed2000

Rotating Gamma System radiosurgery for cerebral arteriovenous malformations.

One hundred and thirty-two patients with cerebral arteriovenous malformations (AVMs) were treated using the Rotating Gamma System, a new radiosurgical system between November 1996 and May 2000. The average size of the AVMs was 23 mm in diameter (range 6 to 69 mm). The mean dose delivered to the AVM margin was 19.2 Gy (range 13 to 25 Gy), and that delivered to the center of the AVMs was 37.6 Gy (range 32.5 to 50 Gy). One hundred and six patients were followed up for an average of 18.4 months (range 5 to 44 months). Five patients (4.7%) experienced rebleeding which took place between 5 and 13 months after treatment, but none of them died from hemorrhage. No bleeding took place after complete angiographic obliteration. Neuroimaging studies showed radiation-induced edema in 19 (22%) of the 87 patients, none of whom had severe permanent neurological deficits. Of the 68 patients followed up for more than one year, 57 underwent angiography at 1 year after treatment. The complete obliteration was demonstrated in 24 patients (42%) at 1 year. Of the 27 patients followed for more than 2 years, 23 patients underwent angiography 2 years after treatment, and complete obliteration was demonstrated in 18 patients (78%). These results are comparable to the results of treatment with other radiosurgical systems.

Adolescent↗
PubMed2000

Combined treatment with stereotactic intracavitary irradiation and gamma knife surgery for craniopharyngiomas.

OBJECT: To evaluate the effectiveness of the combined treatment of stereotactic intracavitary irradiation and Gamma Knife surgery on craniopharyngiomas. PATIENTS AND METHODS: Combined treatment with stereotactic instillation of radioisotopes and Gamma Knife surgery was performed on 46 patients with craniopharyngioma between October 1996 and June 1999. There were 13 solid tumors and 33 mixed solid and cystic tumors. RESULTS: 38 patients (10 solid and 28 mixed) were followed up from 6 months to two years. The tumor control rate was 90% in solid tumors, 85.7% in mixed tumors, 92.1% in the solid segment and 89.5% in total. CONCLUSIONS: Gamma Knife surgery plays an important role in the treatment of the solid component of craniopharyngiomas and the combination of treatment is a simple, safe and effective method for treatment of craniopharyngiomas, especially for the recurrent mixed solid and cystic tumors.

Adolescent↗
PubMed2000

A new function of BMP4: dual role for BMP4 in regulation of Sonic hedgehog expression in the mouse tooth germ.

The murine tooth development is governed by sequential and reciprocal epithelial-mesenchymal interactions. Multiple signaling molecules are expressed in the developing tooth germ and interact each other to mediate the inductive tissue interactions. Among them are Sonic hedgehog (SHH), Bone Morphogenetic Protein-2 (BMP2) and Bone Morphogenetic Protein-4 (BMP4). We have investigated the interactions between these signaling molecules during early tooth development. We found that the expression of Shh and Bmp2 is downregulated at E12.5 and E13.5 in the dental epithelium of the Msx1 mutant tooth germ where Bmp4 expression is significantly reduced in the dental mesenchyme. Inhibition of BMP4 activity by noggin resulted in repression of Shh and Bmp2 in wild-type dental epithelium. When implanted into the dental mesenchyme of Msx1 mutants, beads soaked with BMP4 protein were able to restore the expression of both Shh and Bmp2 in the Msx1 mutant epithelium. These results demonstrated that mesenchymal BMP4 represents one component of the signal acting on the epithelium to maintain Shh and Bmp2 expression. In contrast, BMP4-soaked beads repressed Shh and Bmp2 expression in the wild-type dental epithelium. TUNEL assay indicated that this suppression of gene expression by exogenous BMP4 was not the result of an increase in programmed cell death in the tooth germ. Ectopic expression of human Bmp4 to the dental mesenchyme driven by the mouse Msx1 promoter restored Shh expression in the Msx1 mutant dental epithelium but repressed Shh in the wild-type tooth germ in vivo. We further demonstrated that this regulation of Shh expression by BMP4 is conserved in the mouse developing limb bud. In addition, Shh expression was unaffected in the developing limb buds of the transgenic mice in which a constitutively active Bmpr-IB is ectopically expressed in the forelimb posterior mesenchyme and throughout the hindlimb mesenchyme, suggesting that the repression of Shh expression by BMP4 may not be mediated by BMP receptor-IB. These results provide evidence for a new function of BMP4. BMP4 can act upstream to Shh by regulating Shh expression in mouse developing tooth germ and limb bud. Taken together, our data provide insight into a new regulatory mechanism for Shh expression, and suggest that this BMP4-mediated pathway in Shh regulation may have a general implication in vertebrate organogenesis.

Animals↗
PubMed2000

Integrin alpha 2 beta 1-dependent EGF receptor activation at cell-cell contact sites.

Certain integrins including alpha 2 beta 1 and alpha 3 beta 1 localize to intercellular binding sites, and thus may participate in cell-cell interactions. We demonstrated here the physical and functional associations of integrin alpha 2 beta 1 with epidermal growth factor receptor (EGFR) at intercellular adhesion sites. Immunoprecipitation with anti-integrin alpha 2 antibodies or anti-integrin beta 1 antibody resulted in preferential coprecipitation of EGFR from A431 cell lysates, while anti-EGFR antibody coprecipitated integrin alpha 2 beta 1. Chemical crosslinking confirmed the association of integrin alpha 2 beta 1 and EGFR. Colocalization of integrin alpha 2 beta 1 and EGFR at cell-cell contact sites was observed by double immunofluorescence staining of A431 cells. EGF-induced EGFR stimulation did not affect the association of integrin alpha 2 beta 1 and EGFR. However, immunostaining with the antibody specific to activated-EGFR revealed that EGFR localized at cell-cell contact sites are phosphorylated even in serum-depleted conditions, while EGFR localized to other sites is totally dephosphorylated in the same conditions. The EGFR phosphorylation in cell-cell contact sites observed in a serum-depleted culture was abrogated with a function-blocking antibody of integrin alpha 2, but not with a non-function-blocking alpha 2 antibody or function-blocking alpha 3 antibody. Moreover, the EGFR phosphorylation in serum-depleted conditions was not observed in suspended cells, or largely abrogated in sparse cells, indicating that cell-cell adhesion is required for EGFR phosphorylation. These results indicate that integrin alpha 2 beta 1 not only physically associates with EGFR but also functions in serum-independent EGFR activation at cell-cell contact sites. The present results shed a new light on the role of intercellular integrins in cell-cell interactions.

Cell Communication↗
PubMed2000

[Study on biliary motility in cirrhotic patients with portal hypertension].

OBJECTIVE: To study biliary motility in cirrhotic patients with portal hypertension and analyze the relationship between these biliary motility and the degree of liver function. METHODS: Biliary motility function was detected in 40 patients with portal hypertension and 30 normal controls by using quantitative hepatobiliary scintigraphy. RESULTS: The rate of dysfunction of gallbladder in cirrhotic patients was 52.5%, and it was significantly higher than that in controls (chi(2)=11.92, P<0.01). Compared with the normal controls, the bile's transit in biliary duct of cirrhotic patients was slower (t=11.09, P<0.01), the time of gallbladder visualization became longer (t=5.65, P<0.01), and the gallbladder emptying time was markedly prolonged (t=2.10, P<0.05). A correlation was also seen between these biliary motility and the degree of liver function. CONCLUSION: Cirrhotic patients with portal hypertension often have abnormal motility of gallbladder and biliary duct.

Adult↗