Search PubMed⌕ Search

Biomedical subjects

B Xiao

Publications and source records attributed to B Xiao.

At least 73 records · Page 4Linked to original sources
PubMed1999

Coupling of mGluR/Homer and PSD-95 complexes by the Shank family of postsynaptic density proteins.

Shank is a recently described family of postsynaptic proteins that function as part of the NMDA receptor-associated PSD-95 complex (Naisbitt et al., 1999 [this issue of Neuron]). Here, we report that Shank proteins also bind to Homer. Homer proteins form multivalent complexes that bind proline-rich motifs in group 1 metabotropic glutamate receptors and inositol trisphosphate receptors, thereby coupling these receptors in a signaling complex. A single Homer-binding site is identified in Shank, and Shank and Homer coimmunoprecipitate from brain and colocalize at postsynaptic densities. Moreover, Shank clusters mGluR5 in heterologous cells in the presence of Homer and mediates the coclustering of Homer with PSD-95/GKAP. Thus, Shank may cross-link Homer and PSD-95 complexes in the PSD and play a role in the signaling mechanisms of both mGluRs and NMDA receptors.

Adaptor Proteins, Signal Transducing↗
PubMed1999

Crystal structure of 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase, a potential target for the development of novel antimicrobial agents.

BACKGROUND: Folate cofactors are essential for life. Mammals derive folates from their diet, whereas most microorganisms must synthesize folates de novo. Enzymes of the folate pathway therefore provide ideal targets for the development of antimicrobial agents. 6-Hydroxymethyl-7,8-dihydropterin pyrophosphokinase (HPPK) catalyzes the transfer of pyrophosphate from ATP to 6-hydroxymethyl-7,8-dihydropterin (HP), the first reaction in the folate biosynthetic pathway. RESULTS: The crystal structure of HPPK from Escherichia coli has been determined at 1.5 A resolution with a crystallographic R factor of 0.182. The HPPK molecule has a novel three-layered alpha beta alpha fold that creates a valley approximately 26 A long, 10 A wide and 10 A deep. The active center of HPPK is located in the valley and the substrate-binding sites have been identified with the aid of NMR spectroscopy. The HP-binding site is located at one end of the valley, near Asn55, and is sandwiched between two aromatic sidechains. The ATP-binding site is located at the other end of the valley. The adenine base of ATP is positioned near Leu111 and the ribose and the triphosphate extend across and reach the vicinity of HP. CONCLUSIONS: The HPPK structure provides a framework to elucidate structure/function relationships of the enzyme and to analyze mechanisms of pyrophosphoryl transfer. Furthermore, this work may prove useful in the structure-based design of new antimicrobial agents.

Adenosine Triphosphate↗
PubMed1999

Dendritic cell-derived nitric oxide is involved in IL-4-induced suppression of experimental allergic encephalomyelitis (EAE) in Lewis rats.

Cytokines play a crucial role in initiating and perpetuating EAE, an animal model of multiple sclerosis (MS). A low dose of IL-4, administered by the nasal route over 5 days (100 ng/rat per day) prior to immunization, improved clinical scores of EAE induced in Lewis rats with myelin basic protein (MBP) peptide 68-86 (MBP 68-86). We examined whether dendritic cells (DC) may have contributed to the amelioration of the disease process. These professional antigen-presenting cells (APC) not only activate T cells, but also tolerize T cells to antigens, thereby minimizing autoimmune reactions. We found that IL-4 administration enhanced proliferation of DC. In comparison with DC of PBS-treated rats, DC from IL-4-treated rats secreted high levels of interferon-gamma (IFN-gamma) and IL-10. Nitric oxide (NO) production by DC was also strongly augmented in IL-4-treated rats. In vitro studies showed that IL-4 stimulated DC expansion and that IFN-gamma enhanced NO production by DC. DC-derived NO promoted apoptosis of autoreactive T cells. These results indicate that nasal administration of IL-4 promotes activation of DC and induces production of IFN-gamma and IL-10 by DC. IL-10 suppresses antigen presentation by DC, while IFN-gamma induces NO production by DC which leads to apoptosis in autoreactive T cells. Such a DC-derived negative feedback loop might contribute to the clinical improvement observed in EAE.

Animals↗
PubMed1999

Multiple sclerosis: levels of interleukin-10-secreting blood mononuclear cells are low in untreated patients but augmented during interferon-beta-1b treatment.

The cytokine interleukin (IL)-10 has immune response down-regulatory properties, which include suppression of the synthesis of pro-inflammatory cytokines such as interferon (IFN)-gamma and of major histocompatibility complex (MHC) class II expression on monocytes. To further elucidate the involvement of IL-10 in multiple sclerosis (MS), an enzyme-linked immunospot assay was adopted to enumerate IL-10-secreting mononuclear cells (MNC) in peripheral blood. IFN-gamma secreting MNC were detected in parallel. Levels of IL-10-secreting cells were lower in patients with MS compared with other neurological diseases (OND) and healthy subjects. This difference was seen only in patients with untreated MS, and not in those undergoing treatment with IFN-beta-1b. No differences were observed when subgrouping the patients with MS regarding clinical phase (exacerbation, remission, secondary progression), duration of MS or disability status. Levels of IFN-gamma-secreting blood MNC did not differ in patients with MS, irrespective of treatment with IFN-beta-1b, compared with OND and healthy subjects. Patients with MS, but not the two groups of controls, had elevated numbers of IL-10- and IFN-gamma-secreting cells upon stimulation with MBP compared with culture in the absence of antigen. The data suggest that IL-10 is decreased in MS and that treatment resulting in its up-regulation beneficially influence the disease.

Adult↗
PubMed1999

PCR assay for the inversion causing severe Hemophilia A and its application.

OBJECTIVE: To develop a new technique based on long distance polymerase chain reaction (LD-PCR) to replace Southern blotting method to detect Factor VIII (FVIII) gene inversion leading to severe Hemophilia A (HA) and carrier. METHODS: Four primers P, Q, A&B were designed and synthesized. P&Q is specific for 5' and 3' flanking regions of F8A1 respectively. A&B is specific for 5' and 3' flanking regions of F8A2/F8A3 respectively. LD-PCR with 3 primers and 3 temprature was set up, optimized and used to detect the inversion. RESULTS: The LD-PCR with primers P, Q, A&B, P, Q&B and P, Q&A can be used to detect the gene inversion and discriminate carrier from wild type. A blind analysis of 53 DNA samples from HA families was carried out by the LD-PCR and Southern blotting respectively. Two sets of the results were completely identical. They were 23 cases of inversion, 27 cases of wild type and 3 cases of carriers. The sensitivity and specificity of LD-PCR are both 100%. Three inversion hemizygotes and 4 female carriers were identified from 5 HA families by the LD-PCR technology. CONCLUSIONS: The LD-PCR with primer P, Q&B or P, Q, A&B can be used to detect the gene inversion and the carrier of inversion. Compared with Southern blotting, this technique is simple, rapid, inexpensive, more sensitive, accurate and non-isotopic.

Chromosome Inversion↗
PubMed1999

Amplified fragment length polymorphism analysis on D5S436 locus and its application to linkage analysis in gene diagnosis of asthma.

OBJECTIVES: To detect the polymorphism of D5S436 locus, and to carry out an amplified fragment length polymorphism (Amp-FLP) genotyping linkage analysis in asthma families. METHODS: Allele and genotype frequencies of the high polymorphic D5S436 locus were determined in 92 unrelated Chinese individuals by using polymerase chain reaction (PCR). The amplified fragments were separated by denaturing polyacrylamide gel electrophoresis and silver staining techniques. RESULTS: Eight alleles and 22 genotypes were observed in this population. The heterozygosity was 78.26%. The polymorphism information content (PIC) was 0.76. Amp-FLP genotyping linkage analyses were carried out in four asthma families, demonstrating that the locus was inherited according to Mendel's law and had a clear result. CONCLUSION: The PIC of D5S436 is high in Chinese individuals, so it could be used as a genetic marker of asthma in Chinese and might be useful in the gene diagnosis of asthma.

Alleles↗
PubMed1999

[Apoptosis of CD4(+) T cells during experimental autoimmune neuritis in Wistar rats].

The present study describes apoptosis of T cells in the sciatic nerve in Wistar rats with experimental autoimmune neuritis(EAN). Morphological characterizations of apoptosis were found at the 18th day from onset, peaked at the 22nd day by immunocytochemical analysis. In situ end labeling(ISEL) techniques confirmed the presence of DNA fragmentation in CD4(+) T cells. It is suggested that apoptosis is an important clearance mechanism of infiltrated T cells in the peripheral nervous system(PNS) in EAN.

Animals↗
PubMed1999

[Changes of placental nitric oxide synthase in patients with pregnancy induced hypertension].

The objective of this study was to determine whether the expression of placental endothelial nitric oxide synthase (eNOS) and/or inducible nitric oxide synthase (iNOS) are changed in pregnancy induced hypertension (PIH). The placentas of 32 patients with PIH and 32 normal pregnancies were studied by immunohistochemistry (Avidin-Biotin-Complex method). The results showed there were eNOS and iNOS antigens in placental tissues from PIH and normal pregnancy. They were all localized in placental villi and syncytiotrophoblast cells. The expression of placenta eNOS decreased significantly in patients with PIH as compared with that of normal pregnancy. The expression of placenta eNOS in mild PIH was higher than that of moderate or severe PIH (P < 0.025, P < 0.005, respectively). There was a negative correlation between blood pressure and the expression of eNOS in placenta (P < 0.0005). There was no significant difference between the expression of iNOS in placenta with PIH and that in normal pregnancy. Also, there was no significant difference of the expression of iNOS in placenta between the mild and moderate PIH, or the mild and severe PIH. Furthermore, there was no correlation between blood pressure and the expression of iNOS in placenta with PIH. It is concluded that the decrease of the expression of eNOS in placenta may be associated with the pathogenesis of PIH.

Adult↗
PubMed1999

[Investigation on interaction between Streptococcus sanguis and Porphyromonas gingivalis in specific pathogen-free rats].

OBJECTIVE: To examine whether endogenous S. sanguis could prevent, or reduce the colonization of the virulent P. gingivalis strain. METHODS: First, 10 specific pathogen-free Wistar rats were divided into 2 groups. Doxycycline was administered in the drinking water for 7 days. Successful implantation of the endogenous strain of S. sanguis, isolated from one of the rats before doxycycline administration, and P. gingivalis 381 within 14 days of observation were demonstrated in the rats of each group respectively. Then, 30 SPF rats were divided into 6 groups. Doxycycline was administered in the drinking water for 7 days to all the rats. Afterwards, the rats in group A and B were inoculated orally once a day for 5 days with P. gingivalis, the rats in group C and E were inoculated orally once a day for 5 days with S. sanguis. Then, the rats in group A were inoculated for 5 days with S. sanguis, and rats in group C and D were inoculated for 5 days with P. gingivalis. The rats in group F served as negative control. After inoculation, the levels of S. sanguis and P. gingivalis in the mouths of the rats were determined after 12, 24, 36 hours, 7 days and 14 days. RESULTS: Both pre-colonization of S. sanguis and superinfection with S. sanguis did reduce the level of P. gingivalis in experimental rats. However, the reduction only maintained quite short time, about 36 hours. It was not caused by the decreased level of S. sanguis after 36 hours because the level of S. sanguis kept stable during the observation period of 14 days. CONCLUSION: That S. sanguis function as the effector strain requires the successful implantation of S. sanguis as well as S. sanguis producing antagonistic action efficiently in vivo.

Animals↗
PubMed1999

[Experimental study on carotid artery resection with vascular replacement by an autogenous vein graft].

OBJECTIVE: In order to observe the survival rate and the histologic changes of the reestablished common carotid artery system. METHOD: A planned resection of the carotid artery was done and the common carotid artery system was reestablished by interposing an autogenous external jugular vein graft in 15 white rabbits. RESULT: 12 survived, the other 3 rabbits died from graft thrombosis, the survival rate was 80%. Histologic examination demonstrated the smooth internal tunic in the anastomotic part of the carotid-jugular and no graft thrombosis. Angiography demonstrated the free circulation of the blood and no aneurysm in the anastomotic vein. CONCLUSION: It is concluded that it is possible that in selected patients, a planned resection of the carotid artery with replacement by interposing an autogenous external jugular vein graft will be done.

Anastomosis, Surgical↗
PubMed1999

Phase-1 studies of malariotherapy for HIV infecton.

OBJECTIVE: To determine whether malariotherapy (an old therapy for treatment of neurosyphilis) improves some clinical and laboratory parameters of HIV-positive patients without iatrogenic complications. METHODS: Total 8 asymptomatic HIV-1 positive subjects whose CD4 cell counts were over 250 x 10(6) cells/L were selected for the phase-1 studies of malariotherapy and were intravenously injected Plasmodia vivax to induce artificial malaria. Malaria was terminated with chloroquine after 10 to approximately 20 malarial fever episodes. Cell-bound CD4 levels were measured by APAAP (a solid-phase enzyme essay) and levels of neopterin (NPT), beta-2-microglobulin (B2M), soluble tumor necrosis factor receptor-2 (sTNF-RII), interleukin-2 (IL-2) and HIV P24 antigen were measured by ELISA. Patients were followed up to 24 to approximately 30 months. RESULTS: CD4 levels increased in 5, NPT decreased in 7 of 8 patients; IL-2 increased in 5 of 6 patients after malariotherapy. The total trends of B2M and sTNF-RII basically remained stable. HIV P24 antigen remained undetectable in 6, remained detectably low level in 1 and experienced increase in 1 of 8 patients after malariotherapy. No any severe complications occurred in all 8 patients. CONCLUSIONS: The results indicate that malariotherapy basically is safe for HIV infection and it seems that the therapy improves some immunological parameters of HIV patients.

Adult↗
PubMed1998

Homer regulates the association of group 1 metabotropic glutamate receptors with multivalent complexes of homer-related, synaptic proteins.

Homer is a neuronal immediate early gene (IEG) that is enriched at excitatory synapses and binds group 1 metabotropic glutamate receptors (mGluRs). Here, we characterize a family of Homer-related proteins derived from three distinct genes. Like Homer IEG (now termed Homer 1a), all new members bind group 1 mGluRs. In contrast to Homer 1a, new members are constitutively expressed and encode a C-terminal coiled-coil (CC) domain that mediates self-multimerization. CC-Homers form natural complexes that cross-link mGluRs and are enriched at the postsynaptic density. Homer 1a does not multimerize and blocks the association of mGluRs with CC-Homer complexes. These observations support a model in which the dynamic expression of Homer 1a competes with constitutively expressed CC-Homers to modify synaptic mGluR properties.

Amino Acid Sequence↗
PubMed1998

Homer binds a novel proline-rich motif and links group 1 metabotropic glutamate receptors with IP3 receptors.

Group I metabotropic glutamate receptors (mGluRs) activate PI turnover and thereby trigger intracellular calcium release. Previously, we demonstrated that mGluRs form natural complexes with members of a family of Homer-related synaptic proteins. Here, we present evidence that Homer proteins form a physical tether linking mGluRs with the inositol trisphosphate receptors (IP3R). A novel proline-rich "Homer ligand" (PPXXFr) is identified in group 1 mGluRs and IP3R, and these receptors coimmunoprecipitate as a complex with Homer from brain. Expression of the IEG form of Homer, which lacks the ability to cross-link, modulates mGluR-induced intracellular calcium release. These studies identify a novel mechanism in calcium signaling and provide evidence that an IEG, whose expression is driven by synaptic activity, can directly modify a specific synaptic function.

Amino Acid Sequence↗
PubMed1998

Quality of life and personality in adults with epilepsy.

PURPOSE: This study was undertaken to understand the quality of life, personality, and associated factors in patients with epilepsy. METHODS: 117 patients with epilepsy and 84 healthy people were studied and tested using the Social Support Scale, the General Well-being Schedule, the Life-Event Scale, the Behavior Pattern Scale, and the Eysenck Personality Questionnaire (EPQ). RESULTS: There were no significant differences between the patients with epilepsy and the control group in the Social Support Scale results. The General Well-being Schedule scores were lower for the case patients than for the control group (p < 0.01). Scores for patients with frequent seizures (once a month or more) were lower than those without frequent seizures (less than once per month). The case patients had higher negative scores in the family-related problem section of the Life Events Scale, compared with the control group (p < 0.05). The patients with epilepsy were also more likely to lie (p < 0.05); their emotions were more changeable (p < 0.01), and their character more introverted (p < 0.05), although their behavior patterns were similar to the controls. We also studied associated factors related to personality, general well-being, and familial-negative life-events. CONCLUSIONS: These results provide information about patients with epilepsy that may be useful in their psychological treatment.

Adult↗
PubMed1998

[A comparison study on the sensitivity of lung tumor short-term induction test in three strains of mice].

To compare the sensitivities of lung tumor short-term induction in different strains of mice, the carcinogenicity risk was evaluated with the incidence rate and the average number of tumors. Three different strains of mice (KM, BALB/c and A/J) were injected with a single different dose of urethane i.p. The results demonstrated that the lowest dose for increasing tumor risk was 100 mg/kg in KM, 200 mg/kg in BALB/c, and lower than 25 mg/kg in A/J strain. So, the sensitivity of A/J strain is the highest and that of BALB/c is the lowest.

Animals↗
PubMed1998

[Cerebrospinal fluid cytology of acute viral encephalitis and meningitis].

Using cytological examination, the cerebrospinal fluid(CSF) of 98 patients with acute viral encephalitis was investigated. We found 81.4% activated lymphocytes and 5.8% plasma cells in CSF in the first week. In addition, various lymphoid features were disclosed in association: mitosis, binucleation, abnormal nuclear lobulation, Russell bodies, and morula in plasma cells. These cellular changes specifically existed in CSF of acute viral encephalitis, which were helpful to distinguish the said disease from tuberculous melitis and multiple sclerosis.

Acute Disease↗