Enterovirus A, Human ; pathogenicity ; Enterovirus Infections ; complications ; Humans ; Pulmonary Edema ; etiology ; virology

Anti-Bacterial Agents/therapeutic use* ; Child ; Humans

Humans ; Anti-Bacterial Agents/therapeutic use*

Increasing evidence has revealed that maternal cytomegalovirus (CMV) infection may be associated with neurodevelopmental disorders in offspring.Potential relevance between the placental inflammation and CMV-related autism has been reported by clinical observation.Meanwhile,abnormal expression of Toll-like receptor 2 (TLR2) and TLR4 in placenta of patients with chorioamnionitis was observed in multiple studies.IL-6 and IL-10 are two important maternal inflammatory mediators involved in neurodevelopmental disorders.To investigate whether murine CMV (MCMV) infection causes alterations in placental IL-6/10 and TLR2/4 levels,we analyzed the dynamic changes in gene expression of TLR2/4 and IL-6/10 in placentas following acute MCMV infection.Mouse model of acute MCMV infection during pregnancy was created,and pre-pregnant MCMV infected,lipopolysaccharide (LPS)-treated and uninfected mice were used as controls.At E13.5,E14.5 and E18.5,placentas and fetal brains were harvested and mRNA expression levels of placental TLR2/4 and IL-6/10 were analyzed.The results showed that after acute MCMV infection,the expression levels of placental TLR2/4 and IL-6 were elevated at E13.5,accompanied by obvious placental inflammation and reduction of placenta and fetal brain weights.However,LPS 50 μg/kg could decrease the IL-6 expression at E13.5 and E14.5.This suggests that acute MCMV infection during pregnancy could up-regulate the gene expression of TLR2/4 in placental trophoblasts and activate them to produce more proinflammatory cytokine IL-6.High dose of LPS stimulation (50 tg/kg) during pregnancy can lead to down-regulation of IL-6 levels in the late stage.Imbalance ofIL-6 expression in placenta might be associated with the neurodevelopmental disorders in progeny.

Biomedical Research ; Child ; China ; Cytomegalovirus Infections ; diagnosis ; Diarrhea ; diagnosis ; therapy ; Hepatitis ; diagnosis ; therapy ; Hepatitis B ; transmission ; Humans ; Infectious Disease Medicine ; classification ; Infectious Disease Transmission, Vertical ; prevention & control ; Pediatrics ; classification

OBJECTIVETo investigate the prophylactic, blocking and therapeutic effects of Allitridin on inhibiting HCMV proliferation by measuring the expression level of HCMV IEA in vitro and explore the mechanism of Allitridin anti-HCMVactivity.

METHODSThe cytotocity of Allitridin was evaluated through MTT colorimetry and cell morphology. HCMV IEA levels were quantitatively detected by Flow Cytometry respectively under the following conditions: Allitridin was given before (pretreated for 24 h), during, or after viral inoculation in which serial doses (maximum tolerant concentration, MTC for human embryo lung cells, HEL) of Allitridin was used to treat HCMV infected HLE cells for different durations (24, 48, 72, 96 h) after viral infection.

RESULTThe MTC of Allitridin was 9.60 mg x L(-1). Allitridin remarkably inhibited the expression of HCMV IEA in vitro. Within MTC, the inhibitory rate had a significant correlation with its dosage (r = 0.96). At the time of IEA highest expression (72 h after infection), inhibitory effect was the greatest (inhibitory rate: 89.3%). With pretreatment of Allitridin, the inhibitory rate was 28.6%. When Allitridin was used together with HCMV inoculation, IEA inhibitory rate was only 10.3%.

CONCLUSIONAllitridin can inhibit HCMV, IEA expression in vitro remarkably which is probably one of the major mechanisms of Allitridin anti-HCMV activity because IEAs are the very important regulatory factors for the expression of all HCMV genes. Its therapeutic effect is the best at the peak stage of IE1 gene expression (72 h after infection) but it has low prophylactic and little blocking effect.

Allyl Compounds ; isolation & purification ; pharmacology ; Antiviral Agents ; pharmacology ; Cytomegalovirus ; genetics ; Fibroblasts ; cytology ; metabolism ; virology ; Flow Cytometry ; Garlic ; chemistry ; Gene Expression Regulation, Viral ; drug effects ; Humans ; Immediate-Early Proteins ; metabolism ; Plants, Medicinal ; chemistry ; Sulfides ; isolation & purification ; pharmacology

BACKGROUNDMurine cytomegalovirus (MCMV) early protein M112-113 is involved in viral DNA replication and believed to play a crucial role in the viral pathogenesis. To investigate the biological function of M112-113 protein in the pathogenesis of the brain disorders caused by cytomegalovirus (CMV), a screening for proteins interacting with M112-113 was performed by a yeast two-hybrid system.

METHODSBait plasmid pGBKT7-M112-113 was constructed and transformed into AH109 yeast. After confirmation of the expression of MCMV M112-113 in yeast, the bait yeast was mated with a prey yeast containing mouse brain cDNA library plasmid to screen the proteins interacting with M112-113. Interactions between M112-113 and the obtained proteins were verified by yeast two-hybrid assay and chemiluminescent co-immunoprecipitaion.

RESULTSTwo proteins interacting with M112-113 were identified, including metastasis-associated 1 (MTA1) and zinc finger, CCHC domain containing 18 (ZCCHC18). M112-113 protein could interact with MTA1 or ZCCHC18 in yeast and mammalian cells.

CONCLUSIONThe interactions of M112-113 with MTA1 or ZCCHC18 may be related to the pathogenesis of MCMV-associated disease in central nervous system.

Animals ; Brain ; metabolism ; Cell Line ; Humans ; Immunoprecipitation ; Mice ; Muromegalovirus ; metabolism ; Plasmids ; Protein Binding ; Two-Hybrid System Techniques ; Viral Proteins ; metabolism

OBJECTIVETo investigate the genetic polymorphism of human cytomegalovirus (HCMV) glycoprotein H (gH) from infantile clinical isolates, to analyze the genotypic distribution of gH in different diseases of HCMV infection and try to find the correlations between the diseases and genotypes.

METHODFresh urine specimens were collected from the hospitalized children with different diseases whose blood HCMV-IgM and HCMV-IgG were positive. Virus was isolated from these specimens. Glycoprotein H of harvest clinical isolates was genotyped by nested-PCR combined with restriction fragment length polymorphism (RFLP), the purified PCR products were digested by restriction endonuclease HhaI. The digested products were genotyped by polyacrylamide gel electrophoresis and silver staining. Classification and results of sequencing were compared.

RESULTTotally 102 HCMV clinical isolates were obtained. Glycoprotein H gene of these clinical isolates (43 cases had infantile hepatitis syndrome, 38 cases had anicteric hepatitis, 13 pneumonia, 7 thrombocytopenic purpura, and 1 congenital CMV infection) were positive by nested-PCR, whose positive rate was 100%. The results showed that 62 strains were gH1 genotypes (60.8%), while 40 strains were gH2 (39.2%), mixed type or new genotype was not observed. In infantile hepatitis syndrome (26 clinical isolates were gH1 genotypes, 17 clinical isolates were gH2 genotypes), anicteric hepatitis (25 were gH1, 13 were gH2) and pneumonia (9 were gH1, 4 were gH2), the distribution of HCMV gH genotypes of infantile clinical isolates was consistent with the overall trend (χ(2) = 0.357, P > 0.05). However , the gH2 was more common than gH1 in the clinical isolates of patients with thrombocytopenic purpura (6 were gH2, 1 were gH2, χ(2) = 6.083, P < 0.05).

CONCLUSIONGenotype 1 was the dominant genotype of glycoprotein H in HCMV clinical isolates from our hospital infants. There was no significant difference between the distribution of gH genotypes in infantile hepatitis syndrome, anicteric hepatitis and pneumonia. However, gH2 was the dominant genotype in thrombocytopenic purpura. These findings suggested that there may be a certain relevance between gH genotype and different clinical manifestations.

Amino Acid Sequence ; Base Sequence ; Child, Preschool ; Cytomegalovirus ; classification ; genetics ; isolation & purification ; Cytomegalovirus Infections ; virology ; DNA Primers ; DNA, Viral ; genetics ; Female ; Genotype ; Hepatitis ; virology ; Humans ; Infant ; Infant, Newborn ; Male ; Pneumonia, Viral ; virology ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Polymorphism, Restriction Fragment Length ; Urine ; virology ; Viral Envelope Proteins ; genetics

OBJECTIVETo evaluate the efficacy of intraoperative magnetic resonance imaging (iMRI) and multimodal navigation in surgical resection of glioblastoma.

METHODSBetween February 2009 and July 2010, 76 glioblastoma patients underwent surgical resection guided by iMRI and multimodal navigation. The cohort consisted of 43 male and 33 female patients, with a mean age of 49 years (range: 14-79 years). Rates of gross total resection (GTR) and extent of resection (EoR) were calculated at first and final iMRI scans.Pearson χ(2) test was used to compare the rates of GTR.

RESULTSiMRI and multimodal navigation were successfully implemented in all cases. Rates of GTR were misestimated by neurosurgeons in 24 cases (31.6%), which were confirmed by first iMRI. Total tumor resection were achieved in 20 cases (26.3%) as a result of iMRI scan, increasing the rates of gross total resection from 52.6% to 78.9% (χ(2) = 11.692, P = 0.001). Extent of resection in 28 patients who underwent further tumor resection were increased from 81.5% to 98.1%, leading to the overall extent of resection improved from 92.3% to 98.4%. At 3-month follow-up, 3 cases (3.9%) developed permanent neurologic deficits. The mean clinical follow-up was 15.6 months (range 3.0-45.0 months). The 2-year overall survival rate was 19.7%. The median progression-free survival of gross total resection group was 12 months (95% CI: 10.1-13.9 months), compared with 9 months (95%CI: 7.9-10.1 months) of the subtotal resection group (χ(2) = 4.756, P = 0.029). The overall survival of gross total resection group was 16 months (95% CI: 13.7-18.3 months), compared with 12 months (95% CI: 9.7-14.3 months) of the subtotal resection group (χ(2) = 7.885, P = 0.005).

CONCLUSIONCombined with multimodal navigation, iMRI helps maximize surgical resection of glioblastoma, preserving neurological function while increasing progression-free survival and overall survival.

Adolescent ; Adult ; Aged ; Brain Neoplasms ; surgery ; Female ; Glioblastoma ; surgery ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Monitoring, Intraoperative ; methods ; Neuronavigation ; Young Adult

OBJECTIVETo observe the relationship between serum uric acid and brachial ankle pulse wave velocity (ba-PWV) in Beijing community individuals.

METHODSThis epidemiological survey was performed in residents of two communities from Shijingshan District in Beijing from 2007 to 2008. Cardiovascular risk factors and ba-PWV were measured. Two thousand five hundred and forty three individuals with both ba-PWV and serum uric acid measurements were included. Ba-PWV ≥ 1400 cm/s was defined as abnormal. The individuals were divided into four groups (Q1, Q2, Q3 and Q4 group) according to the gender-specific quartiles of serum uric acid. Univariate logistic regression was used to evaluate the relation between various cardiovascular risk factors and ba-PWV abnormality. Multivariate logistic regression was used to evaluate the relation between serum uric acid and ba-PWV abnormality after adjusting for other cardiovascular risk factors.

RESULTSBody mass index, triglyeride and prevalence of hypertension increased with increasing levels of serum uric acid (all P < 0.01). Univariate logistic regression analysis showed that age, gender, smoking, hypertension, systolic blood pressure, diastolic blood pressure, diabetes, body mass index, total cholesterol, triglyeride and estimated glomerular filtration rate were related with ba-PWV abnormality (all P < 0.01). Compared with Q1 group, ba-PWV abnormality OR value of Q4 group was 1.73 (95%CI: 1.34 - 2.22, P < 0.01). Multivariate logistic regression revealed that ba-PWV abnormality OR value of Q4 group was 1.66 (95%CI: 1.16 - 2.37, P < 0.01 ) after adjusting for age, gender, smoking, hypertension, systolic blood pressure, diastolic blood pressure, diabetes, body mass index, total cholesterol, triglyeride and estimated glomerular filtration rate when compared with Q1 group and OR values were 1.55 (95%CI: 0.88 - 2.74, P > 0.05) and 1.65 (95%CI: 1.04 - 2.64, P < 0.05) in male and female respectively.

CONCLUSIONIncreased serum uric acid was independently associated with ba-PWV abnormality in Beijing community residents.

Aged ; Ankle ; blood supply ; Blood Pressure ; Brachial Artery ; physiology ; Cardiovascular Diseases ; epidemiology ; prevention & control ; China ; epidemiology ; Female ; Humans ; Male ; Middle Aged ; Pulse ; Pulse Wave Analysis ; Risk Factors ; Uric Acid ; blood