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Biomedical subjects

X Yu

Publications and source records attributed to X Yu.

At least 109 records · Page 6Linked to original sources

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

[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↗

[QRS detection based on neural-network].

In this paper, we have developed an adaptive matched filtering algorithm based upon an artificial network (ANN) for QRS detection. We used an ANN adaptive whitening filter to model the lower frequencies of the ECG signals which are inherently nonlinear and non-stationary. The residual signal which contained mostly higher frequency QRS complex energy was then passed through a linear matched filter to detect the location of the QRS complex. The results demonstrate that this ANN whitenting filter is very effective for removing the time-varying, nonlinear noise characteristic of ECG signals. With this novel approach, the detection rate for a very noisy patient record in the MIT/BIH arrhythmia database in 99.2%, which compares favorably to the 97.8% achieved with a band-pass filtering method.

Electrocardiography↗

[The design of axial flow pump].

Axial flow pump has been the hot point of the research field of circulatory support. This article has outlined the basic principle of its design and the methodology of its experimental study, and explained that excellent engineer design, avoiding turbulence, cavitation and wake, and reducing the destroy of red blood cells were the goal to get in design process. The computer-supported design and virtual experiment offered the high efficient tool for the above design. The axial pump has a broad scope in future clinical application.

Computer-Aided Design↗

[Evaluation of performance and blood compatibility of polyethersulfone hollow fiber plasma separator].

In this study, we evaluated the performance and blood compatibility of polyethersulfone hollow fiber membrane plasma separator by animal experiment. Hemolysis did not occur under the usual conditions of plasma separation. The sieving coefficients of total protein, albumin and globulin were over 95%, and about 60% of total plasma were extracted from the whole blood. White blood cells, platelets, fibrinogen, and coagulation factors were decreased during the early stage of plasma separation and appeared to be within acceptable ranges for clinical use.

Animals↗

Effect of lactoperoxidase system on glucosyltransferase D of Streptococcus mutans.

OBJECTIVE: To investigate the effects of the peroxidase system (LP, H2O2, SCN) and its components on the activity of glucosyltransferase D (GtfD) originating from Streptococcus mutans (S. mutans). METHODS: GtfD was incubated in buffered-KCl assay mixture that contained 20 microM dextran and 100 mM sucrose including 14C-glucose. The activity of GtfD was measured with a scintillation counter. The effects of lactoperoxidase system and its components on GtfD activity were examined by incubating different components separately and together with GtfD. RESULTS: The lactoperoxidase system-generated hypothiocyanite (OSCN) had no effect on the activity of streptococcal GtfD, while the lactoperoxidase enzyme inhibited GtfD. The ratio between the 2 enzymes, LP and GtfD, was important for the inhibition. However, if LP was combined with its substrates, SCN and/or a high concentration of H2O2, it enhanced the activity of GtfD. CONCLUSION: Peroxidase-generated antimicrobial agent HOSCN/OSCN is not inhibitory against GtfD, whereas low concentrations of the LP-enzyme inhibit GtfD.

Anti-Bacterial Agents↗

[Detection of hepatitis C virus RNA in the tissue of hepatocellular carcinoma by multiple detection system].

OBJECTIVE: Detection of hepatic HCV RNA in hepatocellular carcinoma (HCC) is difficult, since its expression is very low. Several techniques have been established. However, false positive and negative rates still exist. In this study, we applied several conventional and recently developed detection systems to determine the exact effect of HCV RNA on the development of RCC. METHODS: Immunohistochemistry for HCV core antigen and in situ hybridization for HCV RNA had been performed in 39 cases of HCC. IS-RT-PCR was applied for detection and localization of HCV RNA. We extracted microdissected liver tissues to detect HCV RNA separately in cancerous and pericancerous tissues so that the microscopic origin of the amplicons could be controlled. The serological tests including ELISA and RT-PCR for HCV also were performed in all cases. RESULTS: The positive rate by ELISA (30.8%) was not always consistent with that by RT-PCR(43.6%)from serum samples. The latter was much more sensitive and accurate to reflect existence of HCV RNA. Immunohistochemistry showed expression of RCV core antigen in 15 of 39 HCC cases. In pericancerous tissues, the signals were mainly localized in the cytoplasm of hepatocytes. However, translocated expression of HCV core protein was observed in the nuclei of tumor cells, the translocated rate was 73.3%. According to IS-RT-PCR, the positive signals were located mainly in the cytoplasm of cancer cells, the positive rate in HCC was 53.8%, expression of HCV RNA, serum HCV RNA level was detected to be low or negative. This suggested that serum HCV RNA was not always a good reflection of hepatic HCV RNA in HCC tissues. The microdissection RT-PCR described here gave an equal positive rate (59.0%) of HCV RNA in cancerous and pericancerous tissues. CONCLUSIONS: The high detection rate of HCV RNA in HCC specimens even from seronegative patients confirms the important role of HCV RNA during malignant transformation. IS-RT-PCR is a good detection and localization method to visualize HCV RNA in HCC tissues. The microdissection RT-PCR method has a distinct advantage and we anticipate this method will provide an important evidence to determine whether HCV play a direct or indirect role in hepatocarcinogenesis.

Adult↗

[Decomposition process of Chinese fir stump roots and changes of nutrient concentration].

With space as a substitute for time, the changes of the density of stump sapwoods and heartwoods, and the releasing process of major nutrients during the decomposition of Chinese fir stump roots were investigated. The yearly loss rate of the densities of sapwoods and heartwoods was 2.767 x 10(-2) and 2.255 x 10(-2) respectively during decomposition. The contents of N and P in sapwoods and roots decreased continually, while those in heartwoods increased during the first stage of decomposition, and then decreased. The K concentration in stump roots decreased remarkably during first two years, and the content of organic substances decreased during the whole decomposition process. The N, P and K concentrations in roots, were higher than those in stump sapwoods and heartwoods at the beginning of decomposition, but bet content of organic substance was opposite.

Abies↗

[Tolerance of various geographic populations of brown planthopper to adverse environmental stresses].

The populations of brown planthopper(BPH), Nilaparvata lugens, were collected from Zhejiang, Guangxi and Yunnan provinces to study their tolerance to various adverse environmental stresses. The results indicated that all of these three populations could adapt to the rice variety IR26 bearing resistant gene 1 (Bph1), and Guangxi and Yunnan populations could successfully infest rice varieties ASD7 bearing bph2 and Rathu Heenati bearing Bph3, implying that these two populations had a higher adaptability to resistant rice varieties. The significantly negative relationship between female brachypterous rate and nymphal density in Zhejiang population showed a lower tolerance to high nymphal density of Zhejiang population than that of Guangxi and Yunnan populations. A higher resistance to high temperature and a lower tolerance to starvation were obviously found in Guangxi and Yunnan populations. The resistance to insecticide (Omethoate) of Zhejiang population was little higher than that of Guangxi population. It was suggested that the tolerance of different geographic populations of BPH to various adverse environmental stresses be closely related to their habitat characteristics.

Animals↗