OBJECTIVESevere Epstein-Barr (EB) virus infection is potentially a devastating process that often leads to death encountered in pediatrics recently. Inappropriate control of EB virus replication may cause severe infection resulting in multiple organ dysfunction. However, little information is available on pulmonary complications associated with EB virus infection. The aim of the present study was to investigate severe EB virus (EBV) infection complicated with lung injury in pediatric intensive care unit (PICU), including clinical characteristics, laboratory or imaging feature and outcomes.

METHODA total of 45 children with severe EBV infection seen in PICU of Shanghai Children's Hospital between January 2011 and December 2014 were retrospectively reviewed. According to clinical characteristics and imaging feature, 45 children were divided into non-lung injury group (n =27), lung injury without pulmonary fibrosis group(n = 12) and pulmonary fibrosis group (n = 6).

RESULTIn totally 45 cases of severe EBV infection, 21 (46.7%) were male and 24 (53. 3%) were female, mean age was 2. 4 years; 18 cases were complicated with lung injury, including 8 male and 10 female, median age was 31. 2 months. All of 18 cases presented with fever and cough, 15 of them exhibited dyspnea,12 cases were complicated with gasping, and 6 cases with ARDS. Eight cases accepted mechanical ventilation for acute respiratory distress; 6 cases who developed pulmonary fibrosis had tachypnea, refractory hypoxemia and hypercapnia, severe pulmonary air leak. The average EBV-DNA level in peripheral blood was 4. 42 x 10(6) copies/ml (range: 3. 25 x 10(3) - 6.59 x 10(7) copies/ml). Anti-EBV antibodies were positive in 41 cases, 18 cases were positive (+) for VCA-IgM, 15 cases were VCA-IgG and EA-IgG (+), 8 cases VCA-IgM and VCA-IgG (+). The radiographic findings revealed pulmonary interstitial infiltrates in all 18 cases with lung injury, 4 cases with segmental consolidation and 2 cases showed pleural effusions. HRCT scanning found EBV associated fibrosis including multifocal patches and diffuse ground-glass attenuation in both lungs, reticular opacities and honeycombing changes were observed 4 weeks after illness onset. There were significant differences in respiratory failure, PICU stay (days), Pediatric risk of mortality III (PRISM III) and pediatric clinical illness score(PCIS), serum TNF-α, EBV-DNA levels, percentage of NK cells and CD4+/CD8+ T cell ratio among non-lung injury group, lung injury without pulmonary fibrosis group and pulmonary fibrosis group (X2 =27. 12, F = 85. 23, 78. 23, 88. 68, 323. 80, 7. 35, χ2 = 6. 71, 12. 15; all P < 0. 05). COX regression analysis revealed that EBV-DNA and serum TNF-α levels were correlated with pulmonary fibrosis significantly (OR = 3. 92, P = 0. 04; OR = 5. 95, P = 0. 01). The patients with EBV-associated hemophagocytic lymphohistiocytosis (EBV-HLH) had higher incidence of pulmonary fibrosis compared with non-EB-HLH (70% vs. 13%, χ2 = 4. 82, P = 0. 03). Of 18 cases, 8 cases died, including 3 cases with pulmonary fibrosis. The surviving cases with pulmonary fibrosis needed longer additional oxygen. Chest HRCT imaging of 3 cases with pulmonary fibrosis was improved at 6 months and oxygen therapy was discontinued at 18 months after discharge.

CONCLUSIONEB virus infection complicated with lung injury had higher incidence of respiratory failure, pulmonary fibrosis with a fatal outcome. EBV-DNA and serum TNF-α level were found to be statistically significant indicators of pulmonary fibrosis. Pulmonary fibrosis associated with severe EB virus infection may be reversible.

Antibodies, Viral ; blood ; CD4-CD8 Ratio ; Child, Preschool ; China ; DNA, Viral ; blood ; Epstein-Barr Virus Infections ; pathology ; Female ; Herpesvirus 4, Human ; Humans ; Intensive Care Units, Pediatric ; Killer Cells, Natural ; Lung Injury ; virology ; Lymphohistiocytosis, Hemophagocytic ; pathology ; virology ; Male ; Pulmonary Fibrosis ; pathology ; virology ; Retrospective Studies ; Tumor Necrosis Factor-alpha ; blood

Enterovirus 71 (EV71) is the main causative agent of hand, foot, and mouth disease (HFMD). This article presented the inhibitory activity of pentapeptides on the EV71 infection in rhabdomyosarcoma (RD) and suckling mice. The EV71 VP1 capsid protein expression levels and mRNA levels were analyzed by Western blotting and real-time PCR. The antiviral activity of pentapeptides in vivo was evaluated by weight changes and EV71 VP1 protein expression levels in intestines of suckling mice. Results revealed that the pentapeptide P010157 was able to inhibit EV71 replication in RD cells. After being incubated with the P010157 at a concentration of 100 microg x mL(-1) for 48 h, the level of EV71 vp1 mRNA in RD cells decreased by (92.0 +/- 6.3)%. The estimated EC50 was 2.2 microg x mL(-1). P010157 was able to inhibit EV 71-induced cytopathic effect (CPE) in RD cells. The cytotoxic activity of the compound was evaluated against RD cells by MTS assay. The results showed that P010157 had no obvious toxicity. In addition, the treated mice with P010157 did not exhibit weight loss, as was observed in untreated mice. EV71 replication reduced significantly as revealed by Western blotting. These findings suggest that P010157 could prevent EV71 proliferation in vitro and in vivo. P010157 is a novel compound for antiviral therapies against EV71, which merited further investigation.
Animals ; Antiviral Agents ; pharmacology ; Capsid Proteins ; genetics ; metabolism ; Enterovirus A, Human ; physiology ; Enterovirus Infections ; metabolism ; Humans ; Mice ; Oligopeptides ; pharmacology ; RNA, Messenger ; metabolism ; Rhabdomyosarcoma ; metabolism ; pathology ; virology ; Tumor Cells, Cultured ; Virus Replication ; drug effects

BK virus-associated nephropathy (BKVAN) is one of the major causes of allograft dysfunction in kidney transplant (KT) patients. We compared BKVAN combined with acute rejection (BKVAN/AR) with BKVAN alone in KT patients. We retrospectively analyzed biopsy-proven BKVAN in KT patients from 2000 to 2011 at Seoul National University Hospital. Among 414 biopsies from 951 patients, biopsy-proven BKVAN was found in 14 patients. Nine patients had BKVAN alone, while 5 patients had both BKVAN and acute cellular rejection. BKVAN in the BKVAN alone group was detected later than in BKVAN/AR group (21.77 vs 6.39 months after transplantation, P=0.03). Serum creatinine at diagnosis was similar (2.09 vs 2.00 mg/dL). Histological grade was more advanced in the BKVAN/AR group (P=0.034). Serum load of BKV, dose of immunosuppressants, and tacrolimus level showed a higher tendency in the BKVAN alone group; however it was not statistically significant. After anti-rejection therapy, immunosuppression was reduced in the BKVAN/AR group. Renal functional deterioration over 1 yr after BKVAN diagnosis was similar between the two groups (P=0.665). These findings suggest that the prognosis of BKVAN/AR after anti-rejection therapy followed by anti-BKV therapy might be similar to that of BKVAN alone after anti-BKV therapy.
Acute Disease ; Adult ; Antiviral Agents/therapeutic use ; BK Virus/*physiology ; Creatinine/blood ; Female ; *Graft Rejection/diagnosis/virology ; Humans ; Immunosuppressive Agents/administration & dosage ; Kidney/*virology ; Kidney Diseases/pathology/surgery/*virology ; *Kidney Transplantation ; Male ; Middle Aged ; Polyomavirus Infections/drug therapy/*etiology/pathology ; Retrospective Studies ; Tacrolimus/administration & dosage ; Time Factors ; Transplantation, Homologous/adverse effects ; Tumor Virus Infections/drug therapy/*etiology/pathology

BACKGROUND AND OBJECTIVEEpstein-Barr virus (EBV) has been detected in about 10% of gastric carcinomas. However, the pathogenetic role of EBV in gastric carcinoma is uncertain. This study was to explore the correlation of Fas/FasL expression to the apoptosis of tumor cells and tumor-infiltrating lymphocytes (TIL) in EBV-associated gastric carcinoma (EBVaGC).

METHODSFas/FasL expression in 49 specimens of EBVaGC, 20 specimens of EBV-negative gastric carcinoma (EBVnGC) and 12 specimens of normal gastric mucosa was detected by immunohistochemistry. The apoptotic index (AI) of cells was determined by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labeling (TUNEL).

RESULTSThe positive rates of Fas were 91.7% in normal gastric mucosa and 76.8% in gastric carcinoma (P < 0.05); those of FasL were 16.7% in normal gastric mucosa and 58% in gastric carcinoma (P < 0.05). The positive rate of Fas was significantly lower in EBVaGC than in EBVnGC (71.4% vs. 90.0%, P < 0.05). The positive rate of FasL in EBVaGC was significantly higher than that in EBVnGC (63.2% vs. 45%, P < 0.05). The AI of EBVaGC cells was significantly lower than that of EBVnGC cells (P = 0.002). The number and AI of TIL in EBVaGC were higher than those in EBVnGC (P < 0.05). The AI of TIL was positively correlated with the level of FasL expression in tumor cells (r=0.237, P = 0.028).

CONCLUSIONUp-regulation of FasL expression and decrease of TIL apoptosis in EBVaGC may facilitate the escape of tumor cells from the host immunosurveillance, and it might contribute to the development and progression of carcinoma.

Adult ; Apoptosis ; Epstein-Barr Virus Infections ; Fas Ligand Protein ; metabolism ; Female ; Herpesvirus 4, Human ; isolation & purification ; Humans ; Immunohistochemistry ; Immunologic Surveillance ; In Situ Nick-End Labeling ; Lymphocytes, Tumor-Infiltrating ; pathology ; Male ; Middle Aged ; Stomach Neoplasms ; metabolism ; pathology ; virology ; Tumor Escape ; fas Receptor ; metabolism

BK virus (BKV) is a subtype of papovaviridae. The latent and asymptomatic infection of BKV is common among healthy people. The incidence of BKV re-activation in renal transplant recipients ranges 10%-68%. About 1%-7% of renal transplant recipients will suffer from BKV-associated nephropathy (BKVAN), and half of them will experience graft failure. This paper summarizes the re-activation mechanism of BKV as well as the risk factors, pathology, diagnosis, and treatment of BKVAN.
BK Virus ; physiology ; Humans ; Kidney ; pathology ; virology ; Kidney Transplantation ; Polyomavirus Infections ; diagnosis ; pathology ; therapy ; Postoperative Complications ; diagnosis ; pathology ; therapy ; virology ; Risk Factors ; Tumor Virus Infections ; diagnosis ; pathology ; therapy ; Virus Activation

In order to research into the cytology mechanism of anti-virus action of total flavone of Scutellaria barbata (TFSB), the effects of TFSB on host cells membrane potential, Na(+)-K(+)-ATPase activity and membrane fluidity after parainfluenza virus type1 (PIV-1) infection were studied. The changes of membrane potential which was fluorescent labeled with DiBAC4(3) and its changes were measured by flow cytometer. Phosphorus determination method and spectrophotometry were used to measure the Na(+)-K(+)-ATPase activity of Hep-2 cells membrane after PIV-1 infection. Hep-2 cells membrane phospholipids were fluorescent labeled with NBD-C6-HPC and membrane fluidity was measured by confocal scanning laser microscope. The result demonstrated that post PIV-1 infection membrane potential decreased significantly and the membrane was in a state of hyperpolarization, Na(+)-K(+)-ATPase activity increased significantly and membrane fluidity decreased significantly. There was no apparent interfere effect of TFSB on the changes of membrane potential and Na(+)-K(+)-ATPase activity after PIV-1 infection, while membrane fluidity improved significantly. It was indicated that the cytology mechanism of PIV-1 infection might be related to membrane hyperpolarization, Na(+)-K(+)-ATPase activity increase and membrane fluidity decrease. TFSB can improve membrane fluidity and prevent the infection by protecting the cell membrane. But it is possible that the anti-PIV-1 mechanisms of TFSB had nothing to do with membrane potential and Na(+)-K(+)-ATPase activity.
Antiviral Agents ; isolation & purification ; pharmacology ; Cell Line, Tumor ; Cell Membrane ; drug effects ; Flavones ; isolation & purification ; pharmacology ; Humans ; Laryngeal Neoplasms ; pathology ; virology ; Membrane Fluidity ; drug effects ; Membrane Potentials ; drug effects ; Parainfluenza Virus 1, Human ; drug effects ; Phospholipids ; metabolism ; Plants, Medicinal ; chemistry ; Respirovirus Infections ; drug therapy ; Scutellaria ; chemistry ; Sodium-Potassium-Exchanging ATPase ; metabolism

OBJECTIVETo investigate the correlation between the presence of human papillomavirus (HPV) DNA in the lymph nodes and histopathologically confirmed metastasis of early-stage cervical carcinoma.

METHODSHPV L1 gene fragment in paraffin-embedded tissue specimens of the primary tumor and pelvic lymph nodes from 31 patients with cervical cancer was amplified using HPV-specific PCR with general consensus primers GP5+/GP6+. The type of HPV was identified by sequence analysis of the PCR products, and the correlation between the presence of HPV DNA in the lymph node and the clinicopathological indices of cervical carcinoma was analyzed.

RESULTSThe positivity rate of HPV DNA in the pelvic lymph nodes was 58.1% in the 31 patients, and in 13 of the patients with confirmed metastasis, the detection rate was 84.6% as compared with the rate of 27.8% in the other 18 patients without metastases. The presence of HPV DNA in the lymph node was associated with histologically confirmed metastases. The results of both HPV DNA detection and pathological examination indicated that the obturator, internal iliac and external iliac lymph nodes were more liable to be positive for HPV DNA, accounting for over 90% of the positivity.

CONCLUSIONHPV DNA detection in the pelvic lymph nodes is a helpful predictive factor of metastases, and the obturator, internal iliac and external iliac lymph nodes are the among the most vulnerable lymph nodes of metastatic involvement by early-stage cervical carcinoma.

Adult ; DNA, Viral ; analysis ; genetics ; Female ; Host-Pathogen Interactions ; Humans ; Lymph Nodes ; pathology ; virology ; Lymphatic Metastasis ; Middle Aged ; Papillomaviridae ; genetics ; physiology ; Papillomavirus Infections ; pathology ; virology ; Polymerase Chain Reaction ; Tumor Virus Infections ; pathology ; virology ; Uterine Cervical Neoplasms ; pathology ; virology

OBJECTIVETo investigate whether simian virus 40 (SV40) was related to patients of malignant mesothelioma in China.

METHODSParaffin-embeded samples of 17 patients with malignant mesothelioma were collected. After isolation of DNA from paraffin blocks, polymerase chain reaction (PCR) analyses were performed using three different sets of primer for detection of SV40 large T antigen gene. These samples were also immunohistochemically evaluated for expression of SV40 TAg protein with two different anti-SV40 Tag (Pab101 and Ab-2).

RESULTSOnly one of the three primer pairs successfully amplified SV40 genome in three malignant mesothelioma samples. No immunopositive staining for SV40 TAg was found in any of the samples.

CONCLUSIONSThe study shows that malignant mesothelioma in China may be independent of SV40 infection.

Adult ; Aged ; Antigens, Viral, Tumor ; genetics ; metabolism ; China ; Female ; Host-Pathogen Interactions ; Humans ; Immunohistochemistry ; Male ; Mesothelioma ; pathology ; virology ; Middle Aged ; Polymerase Chain Reaction ; Polyomavirus Infections ; pathology ; virology ; Simian virus 40 ; genetics ; immunology ; physiology ; Tumor Virus Infections ; pathology ; virology ; Young Adult

BACKGROUNDTo study the difference in gene expression between the EBV associated gastric carcinoma (EBVaGC) tissues. To explore the mechanism of gastric carcinoma pathogenesis initiated by EBV.

METHODSIn situ hybridization was used to study the frequencies of EBV small RNA expression in 155 cases of gastric carcinoma tissues. The expression levels of P53 protein and P21WAF1 protein were detected by immunohistochemistry in all gastric carcinoma tissues.

RESULTSThe expression of EBV small RNA was positive in 10 out of 155 cases (6.45%). The expression of P53 protein was weakly positive in 4 of the 10 cases. The expression level of P53 protein in EBVaGC was much lower than that in EBVnGC and was weakly positive in 30 of 145 cases with EBVnGC). P21WAF1 expression was detected in 7 of 10 cases with EBVaGC, but in 55 out of 145 cases with EBVaGC, P21WAF1 expression in EBVaGC was much higher than that in EBVnGC.

CONCLUSIONThere seems existing a special mechanism of pathogenesis in EBVaGC. In which P53 gene mutation may not play an important role.

Epstein-Barr Virus Infections ; metabolism ; pathology ; virology ; Herpesvirus 4, Human ; genetics ; physiology ; Host-Pathogen Interactions ; Humans ; Immunohistochemistry ; In Situ Hybridization ; Proto-Oncogene Proteins c-met ; metabolism ; RNA, Viral ; genetics ; Stomach Neoplasms ; metabolism ; pathology ; virology ; Tumor Suppressor Protein p53 ; metabolism

Animals ; Child ; Epstein-Barr Virus Infections ; pathology ; Hodgkin Disease ; pathology ; virology ; Humans ; Infant, Newborn ; Kidney Neoplasms ; classification ; pathology ; Neuroblastoma ; classification ; metabolism ; pathology ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Rhabdomyosarcoma ; classification ; pathology ; Wilms Tumor ; classification ; pathology