MedWorm: Adenoviruses

Gene Therapy Improves Vision in Second Eye of 3 AdultsGene Therapy Improves Vision in Second Eye of 3 Adults

Medscape Today Headlines — Wed, 08 Feb 2012 19:27:34 +0100

The RPE65 gene delivered in an adeno-associated virus vector has safely improved vision in a second eye for patients with Leber congenital amaurosis type 2. Medscape Medical News (Source: Medscape Today Headlines)

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Small Interference RNA Targeting TLR4 Gene Effectively Attenuates Pulmonary Inflammation in a Rat Model

Comparative and Functional Genomics — Mon, 06 Feb 2012 14:15:44 +0100

Conclusion. TLR4 plays a critical role in LPS-induced ALI, and transfection of Ad-siTLR4 can effectively downregulate TLR4 expression in vitro and in vivo, accompanied by alleviation of LPS-induced lung injury. These findings suggest that TLR4 may serve as a potential target in the treatment of ALI and RNA interfering targeting TLR4 expression represents a therapeutic strategy. (Source: Comparative and Functional Genomics)

The Perinatal Infection of Cytomegalovirus Is an Important Etiology for Biliary Atresia in China

Clinical Pediatrics — Mon, 06 Feb 2012 05:00:00 +0100

Conclusion. Human intrahepatic biliary epithelial cell is the target cell of HCMV. The etiology of biliary atresia is probably multifactorial. The perinatal infection of HCMV is one of the important etiologies for biliary atresia in China. (Source: Clinical Pediatrics)

Enhancing lysosome biogenesis attenuates BNIP3-induced cardiomyocyte death.

Autophagy — Sun, 05 Feb 2012 07:12:40 +0100

Authors: Ma X, Godar RJ, Liu H, Diwan A Abstract Hypoxia-inducible pro-death protein BNIP3 (BCL-2/adenovirus E1B 19-kDa interacting protein 3), provokes mitochondrial permeabilization causing cardiomyocyte death in ischemia-reperfusion injury. Inhibition of autophagy accelerates BNIP3-induced cell death, by preventing removal of damaged mitochondria. We tested the hypothesis that stimulating autophagy will attenuate BNIP3-induced cardiomyocyte death. Neonatal rat cardiac myocytes (NRCMs) were adenovirally transduced with BNIP3 (or LacZ as control; at multiplicity of infection = 100); and autophagy was stimulated with rapamycin (100 nM). Cell death was assessed at 48 h. BNIP3 expression increased autophagosome abundance 8-fold and caused a 3.6-fold increase in cardiomyocyte death as...

C/EBP-α ameliorates CCl4-induced liver fibrosis in mice through promoting apoptosis of hepatic stellate cells with little apoptotic effect on hepatocytes in vitro and in vivo

Apoptosis — Fri, 03 Feb 2012 17:12:22 +0100

This study investigated whether C/EBP-α exerts different apoptotic effects on hepatocytes and HSCs in vitro and in vivo. An adenovirus vector-expressing C/EBP-α gene was constructed, and a rat hepatic stellate cell lines (HSC-T6) and hepatocytes were transfected. A CCl4-induced liver fibrosis model in mice was also utilized. C/EBP-α induced apoptosis in hepatocytes and HSCs, but a significant difference between these cell types was observed in vitro. The mitochondrial pathway was involved in the apoptotic process and was predominant in HSC-T6 apoptosis. In the CCl4-induced mice liver fibrosis model, the administration of Ad-C/EBP-α decreased extracellular matrix deposition, including collagen and hydroxyproline content, and γ-GT levels, a marker of liver damage, were reduced sign...

Deletion of Fas protects islet beta cells from cytotoxic effects of human islet amyloid polypeptide

Diabetologia — Thu, 02 Feb 2012 18:12:53 +0100

Conclusions/interpretation The aggregation of biosynthetic hIAPP produced in islets induces beta cell apoptosis, at least partially, via Fas upregulation and the Fas-mediated apoptotic pathway. Deletion of Fas protects islet beta cells from the cytotoxic effects of endogenously secreted (and exogenously applied) hIAPP. Content Type Journal ArticleCategory ArticlePages 1-13DOI 10.1007/s00125-012-2451-2Authors Y. J. Park, Department of Surgery, Faculty of Medicine, University of British Columbia, Jim Pattison Pavilion, Vancouver General Hospital, 910 W 10th Ave, Vancouver, BC, Canada V5Z 4E3S. Lee, Department of Surgery, Faculty of Medicine, University of British Columbia, Jim Pattison Pavilion, Vancouver General Hospital, 910 W 10th Ave, Vancouver, BC, Canada V5Z 4E3T...

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The recombinant lectin-like domain of thrombomodulin inhibits angiogenesis through interaction with Lewis Y antigen

Blood — Thu, 02 Feb 2012 05:00:00 +0100

Lewis Y Ag (LeY) is a cell-surface tetrasaccharide that participates in angiogenesis. Recently, we demonstrated that LeY is a specific ligand of the recombinant lectin-like domain of thrombomodulin (TM). However, the biologic function of interaction between LeY and TM in endothelial cells has never been investigated. Therefore, the role of LeY in tube formation and the role of the recombinant lectin-like domain of TM—TM domain 1 (rTMD1)—in antiangiogenesis were investigated. The recombinant TM ectodomain exhibited lower angiogenic activity than did the recombinant TM domains 2 and 3. rTMD1 interacted with soluble LeY and membrane-bound LeY and inhibited soluble LeY-mediated chemotaxis of endothelial cells. LeY was highly expressed on membrane ruffles and protrusions during tube...

Protective Effects of Adeno-associated Virus Mediated Brain-derived Neurotrophic Factor Expression on Retinal Ganglion Cells in Diabetic Rats.

Cellular and Molecular Neurobiology — Thu, 02 Feb 2012 05:00:00 +0100

Authors: Gong Y, Chang ZP, Ren RT, Wei SH, Zhou HF, Chen XF, Hou BK, Jin X, Zhang MN Abstract Adeno-associated virus vector plasmid carrying the expression cassette of brain-derived neurotrophic factor (BDNF), pAAV-BDNF, was constructed and packaged into recombinant adeno-associated virus (rAAV-BDNF). The rAAV-BDNF was intravitreally injected into streptzotocin (STZ)-induced diabetic Sprague-Dawley (SD) Rats. Data showed that over-expression of BDNF could increase alive retinal ganglion cell (RGC) number and improve its function in streptzotocin(STZ)-induced diabetic rats, which might be a new method to treat diabetic neuropathy and retinopathy. PMID: 22297541 [PubMed - as supplied by publisher] (Source: Cellular and Molecular Neurobiology)

Phosphatase PTEN is critically involved in post-myocardial infarction remodeling through the Akt/interleukin-10 signaling pathway

Basic Research in Cardiology — Wed, 01 Feb 2012 17:09:57 +0100

In conclusion, PTEN is critically involved in post-MI remodeling through the Akt/IL-10 signaling pathway. Therefore, targeting PTEN may be an effective approach to post-MI remodeling. Content Type Journal ArticleCategory Original ContributionPages 1-15DOI 10.1007/s00395-012-0248-6Authors Nirmal Parajuli, Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, 720 Rutland Avenue, Ross 333, Baltimore, MD 21205, USAYuan Yuan, Department of Cardiology, Forth Military Medical University Xijing Hospital, Xian, Shaanxi, ChinaXiaoxu Zheng, Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, 720 Rutland Avenue, Ross 333, Baltimore, MD 21205, USADjahida Bedja, Department of Pathology, Johns Hopkins University Schoo...

Sublingual immunization with adenovirus F protein-based vaccines stimulates protective immunity against botulinum neurotoxin A intoxication

International Immunology — Wed, 01 Feb 2012 05:00:00 +0100

This study shows that s.l. immunization with Ad2F-based vaccines is effective in conferring protective immunity. (Source: International Immunology)

Adenovirus-mediated delivery of CALR and MAGE-A3 inhibits invasion and angiogenesis of glioblastoma cell line U87

Journal of Experimental and Clinical Cancer Research — Wed, 01 Feb 2012 05:00:00 +0100

Conclusion: Although Ad-CALR/MAGE-A3 and Ad-CALR demonstrated antiangiogenic effects on U87 cells, the repression of invasion was significant only in Ad-CALR/MAGE-A3-treated cells. To our knowledge, this is the first description of a role for combined CALR and MAGE-A3 in the anti-invasion and antiangiogenesis of U87. (Source: Journal of Experimental and Clinical Cancer Research)

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Simultaneous presence of human herpesvirus 6 and adenovirus infections in intestinal intussusception of young children

Acta Paediatrica — Wed, 01 Feb 2012 05:00:00 +0100

Conclusions: A statistically significant association was observed between adenovirus and childhood intussusception. HHV‐6 was a common finding and occurred concomitantly with other viruses. A simultaneous infection with HHV‐6 and adenovirus carried the highest risk for intussusception.© 2012 The Author(s)/Acta Pædiatrica © 2012 Foundation Acta Pædiatrica (Source: Acta Paediatrica)

Presence of interferon-α at the time of infection alters the innate and adaptive immune response to porcine reproductive and respiratory syndrome virus.

Clinical and Vaccine Immunology — Wed, 01 Feb 2012 05:00:00 +0100

Authors: Brockmeier SL, Loving CL, Nelson EA, Miller LC, Nicholson TL, Register KB, Grubman MJ, Brough DE, Kehrli ME Abstract Porcine reproductive and respiratory syndrome (PRRS) is one of the most devastating and costly diseases to the swine industry world-wide. Overall, the adaptive immune response to PRRS virus (PRRSV) is weak, which results in delayed elimination of virus from the host and inferior vaccine protection. PRRSV has been shown to induce a meager interferon (IFN)-α response, and we hypothesized that elevated IFN-α levels early in infection would shorten the induction time and increase elements of the adaptive immune response. To test this, we measured both antibody and cell mediated immunity in pigs after the administration of a nonreplicating human adenovirus type...

PVN adenovirus-siRNA injections silencing either NOX2 or NOX4 attenuate aldosterone/NaCl-induced hypertension in mice

AJP: Heart and Circulatory Physiology — Tue, 31 Jan 2012 05:00:00 +0100

Mineralocorticoid excess increases superoxide production by activating NADPH oxidase (NOX), and intracerebroventricular infusions of NADPH oxidase inhibitors attenuate aldosterone (Aldo)/salt-induced hypertension. It has been hypothesized that increased reactive oxygen species (ROS) in the brain may be a key mechanism in the development of hypertension. The present study investigated the brain regional specificity of NADPH oxidase and the role of NOX2 and NOX4 NADPH oxidase subunits in the hypothalamic paraventricular nucleus (PVN) in Aldo/salt-induced hypertension. PVN injections of adenoviral vectors expressing small interfering (si)RNA targeting NOX2 (AdsiRNA-NOX2) or NOX4 (AdsiRNA-NOX4) mRNAs were used to knock down NOX2 and NOX4 proteins. Three days later, delivery of Aldo (0.2 mg&mid...

The C-terminal region of E1A: a molecular tool for cellular cartography.

Biochemistry and Cell Biology — Tue, 31 Jan 2012 05:00:00 +0100

Authors: Yousef AF, Fonseca GJ, Cohen MJ, Mymryk JS Abstract The adenovirus E1A proteins function via protein-protein interactions. By making many connections with the cellular protein network, individual modules of this virally encoded hub reprogram numerous aspects of cell function and behavior. Although many of these interactions have been thoroughly studied, those mediated by the C-terminal region of E1A are less well understood. This review focuses on how this region of E1A affects cell cycle progression, apoptosis, senescence, transformation, and conversion of cells to an epithelial state through interactions with CTBP1/2, DYRK1A/B, FOXK1/2, and importin-α. Furthermore, novel potential pathways that the C-terminus of E1A influences through these connections with the cellular...

Role of monokine induced by interferon‐γ in liver injury induced by hepatitis B virus in mice

Journal of Viral Hepatitis — Sun, 29 Jan 2012 22:39:21 +0100

In conclusion, through NF‐κB activation, HBV induced Mig expression in vivo, which recruited peripheral inflammatory cells to the liver and resulted in liver damage. Phosphorylation of phosphoinositide 3‐kinase/Akt, ERK and JNK but not p38 might involved in the molecular mechanisms underlying HBV induced Mig expression in vivo. (Source: Journal of Viral Hepatitis)

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A recombinant adenovirus expressing immunodominant TB antigens can significantly enhance BCG-induced human immunity.

Vaccine — Sun, 29 Jan 2012 05:00:00 +0100

CONCLUSIONS: Our results indicate that AERAS-402 is a promising TB vaccine candidate that can significantly enhance both CD4(+) and CD8(+) TB-specific T cell responses after BCG priming. ClinicalTrials.gov Identifier: NCT01378312. PMID: 22296955 [PubMed - as supplied by publisher] (Source: Vaccine)

Adenovirus-expressed preS2 antibody inhibits hepatitis B virus infection and hepatic carcinogenesis.

World Journal of Gastroenterology : WJG — Sat, 28 Jan 2012 05:00:00 +0100

CONCLUSION: Adenovirus-mediated HBV preS2Ab expression could inhibit HBV infection in L02 cells, and then inhibit DEN-induced hepatocellular carcinogenesis and protect hepatic function in HBV transgenic mice. PMID: 22294841 [PubMed - in process] (Source: World Journal of Gastroenterology : WJG)

Adenoviruses - Viruses that Affect Children and Adults

Disabled World — Fri, 27 Jan 2012 14:15:22 +0100

Adenoviruses are common and can cause illness in both children and adults. While the majority of the illnesses people experience are not serious, adenoviruses cause respiratory illness most of the time. The viruses can also cause diarrhea, fever, bladder infection, rash illness, and pink eye. (Source: Disabled World)

Immunological mechanisms of oncolytic adenoviral therapy

EurekAlert! - Biology — Fri, 27 Jan 2012 05:00:00 +0100

(Science in China Press) The use of oncolytic adenovirus provides a novel attractive strategy for cancer therapy, but the mechanisms underlying the therapeutic effects are complicated and largely unknown. A paper in the first issue of Vol. 57 of Chinese Science Bulletin demonstrates that the therapeutic effects of oncolytic adenovirus depend on the CD8+ T cell response. (Source: EurekAlert! - Biology)

Adenovirus-mediated Aurora A shRNA driven by stathmin promoter suppressed tumor growth and enhanced paclitaxel chemotherapy sensitivity in human breast carcinoma cells

Cancer Gene Therapy — Fri, 27 Jan 2012 05:00:00 +0100

Authors: M Long, G Yin, L Liu, F Lin, X Wang, J Ren, J Wei, K Dong & H Zhang (Source: Cancer Gene Therapy)

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[Newsdesk] Research brief

The Lancet Infectious Diseases — Thu, 26 Jan 2012 23:05:13 +0100

Vaccines based on human adenovirus 5 (Ad5) induce protective immune responses against several pathogens in animal models, but the neutralising antibodies to Ad5 that most people make are likely to impair the immunological potency of such vaccines. To circumvent this potential problem, researchers have isolated more than 1000 chimpanzee adenovirus strains. Vaccine vectors derived from some of these viruses induce potent cellular immunity in mice. Moreover, in a phase 1 clinical trial, a chimpanzee adenovirus-based vector expressing non-structural hepatitis C virus (HCV) proteins induced broad, sustained T-cell responses to HCV. (Source: The Lancet Infectious Diseases)

Down-regulation of coxsakie and adenovirus receptor during embryo implantation

Journal of Huazhong University of Science and Technology -- Medical Sciences -- — Thu, 26 Jan 2012 16:50:06 +0100

In this study, real-time PCR and immunohistochemistry were used to detect coxsakie and adenovirus receptor (CAR) expression. Both localization and quantity were evaluated in the uteri obtained at days post coitus (dpc) 2.5, 4.5, 6.5, 8.5. Outcome of PCR was assessed by 2−ΔΔCt method. Image Pro-Plus 6.0 software was used for quantifying mean density of CAR expression in immunohistochemical sections. We found relatively weak CAR expression in the mouse uteri during implantation window. PCR and immunohistochemistry revealed highest CAR expression was detected on dpc 2.5 followed by down-regulation of CAR at dpc 4.5 and 6.5 (with significant difference). At dpc 8.5, CAR expression was increased slightly again. It is concluded that during implantation, the expression of CAR mRNA and p...

Overexpression of GDF5 through an Adenovirus Vector Stimulates Osteogenesis of Human Mesenchymal Stem Cells in vitro and in vivo

Karger Publishers — Thu, 26 Jan 2012 12:50:45 +0100

Cells Tissues Organs (DOI:10.1159/000330791) (Source: Karger Publishers)

Protective immunity against tularemia provided by an adenovirus-vectored vaccine expressing Tul4 of Francisella tularensis.

Clinical and Vaccine Immunology — Wed, 25 Jan 2012 05:00:00 +0100

In this study, we have constructed a replication incompetent adenovirus, Ad/opt-Tul4, encoding a codon-optimized gene for expression of the membrane protein, Tul4, of F. tularensis LVS. Its ability to protect against lethal challenge and its immunogenicity were evaluated in a murine model. An intramuscular injection of a single dose (1×10(7) PFU) of Ad/opt-Tul4 elicited a robust Tul4-specific antibody response. Assays suggest a Th1-driven response. A single dose elicited 20% protection against challenge with 100×LD50 F. tularensis LVS; two additional booster shots resulted in 60% protection. In comparison, three doses of 5μg recombinant Tul4 protein did not elicit significant protection against challenge. Therefore, the Ad/opt-Tul4 vaccine was more effective than the protein vaccine, an...

Downregulation of Mdm2 and Mdm4 enhances viral gene expression during adenovirus infection.

Cell Cycle — Tue, 24 Jan 2012 09:52:50 +0100

Authors: Yang H, Zheng Z, Zhao L, Li Q, Liao D Abstract Successful viral replication entails elimination or bypass of host antiviral mechanisms. Here, we show that shRNA-mediated knockdown of murine double minute (Mdm2) and its paralog Mdm4 enhanced the expression of early and late viral gene products during adenovirus (HAdV) infection. Remarkably, whereas the expression of HAdV genes was low in p53-deficient mouse embryonic fibroblasts (p53KO MEFs), the HAdV early gene products were efficiently expressed in Mdm2/p53 double-knockout (DKO) and Mdm4/p53 DKO MEFs, and viral capsid proteins were produced in Mdm2/p53 DKO MEFs. Thus, Mdm2 and Mdm4 seem to have potent antiviral property. In cells infected with wt HAdV or a mutant virus lacking the E1B-55K gene (dl 1520), both Mdm2 and Mdm...

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Identification of adeno-associated viral vectors suitable for intestinal gene delivery and modulation of experimental colitis

AJP: Gastrointestinal and Liver Physiology — Tue, 24 Jan 2012 05:00:00 +0100

This study identifies novel AAV pseudotypes with small intestine and colon tropism and sustained transgene expression capable of modulating mucosal inflammation in a murine model of enterocolitis. (Source: AJP: Gastrointestinal and Liver Physiology)

Rapamycin prevents the mutant huntingtin-suppressed GLT-1 expression in cultured astrocytes.

Acta Pharmacologica Sinica — Mon, 23 Jan 2012 05:00:00 +0100

Conclusion:Rapamcin, an autophagy stimulator, can prevent the suppression of GLT-1 expression and glutamate uptake by mutant Htt-552 in cultured astrocytes. PMID: 22266730 [PubMed - as supplied by publisher] (Source: Acta Pharmacologica Sinica)

Migratory sub-populations of afferent lymphatic dendritic cells differ in their interactions with Mycobacterium bovis Bacille Calmette Guerin.

Vaccine — Mon, 23 Jan 2012 05:00:00 +0100

This study further extends our understanding of the biology of migrating DC, identifies potential explanations for the modest success of BCG vaccination and demonstrates that targeted delivery of antigens via adenoviruses to DC can improve antigen presentation. PMID: 22281103 [PubMed - as supplied by publisher] (Source: Vaccine)

Risk Factors for Molecular Detection of Adenovirus in Pediatric Hematopoietic Stem Cell Transplant Recipients.

Adv Data — Mon, 23 Jan 2012 05:00:00 +0100

Authors: Watson T, Macdonald D, Song X, Bromwich K, Campos J, Sande J, Debiasi RL Abstract Adenovirus (AdV) infections are a major cause of morbidity and mortality in hematopoietic stem cell transplant HSCT) patients. To evaluate the use of molecular AdV testing in HSCT at our institution and identify risk factors for AdV viremia and disease, we performed a retrospective cohort study of all HSCT patients who had undergone AdV polymerase chain reaction (PCR) testing, over a two year period. Two cohorts were identified: Cohort 1 consisted of patients testing positive for AdV (n=7); Cohort 2 consisted of patients testing negative (n=36). Overall patient characteristics were not statistically different between cohorts. The following medication exposures were identified as risk factors ...

Linkage of Cardiac Gene Expression Profiles and ETS2 with Lifespan Variability in Rats

Aging Cell — Thu, 19 Jan 2012 13:50:52 +0100

This article is a U.S. Government work and is in the public domain in the USA (Source: Aging Cell)

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The transcription factor Erg regulates expression of histone deacetylase 6 and multiple pathways involved in endothelial cell migration and angiogenesis

Blood — Thu, 19 Jan 2012 05:00:00 +0100

The endothelial ETS transcription factor Erg plays an important role in homeostasis and angiogenesis by regulating many endothelial functions including survival and junction stability. Here we show that Erg regulates endothelial cell (EC) migration. Transcriptome profiling of Erg-deficient ECs identified ~ 80 genes involved in cell migration as candidate Erg targets, including many regulators of Rho- GTPases. Inhibition of Erg expression in HUVECs resulted in decreased migration in vitro, while Erg overexpression using adenovirus caused increased migra-tion. Live-cell imaging of Erg-deficient HUVECs showed a reduction in lamellipodia, in line with decreased motility. Both actin and tubulin cytoskeletons were disrupted in Erg-deficient ECs, with a dramatic increase in tubulin acetylation. A...

Zinc-finger nuclease-mediated gene correction using single AAV vector transduction and enhancement by Food and Drug Administration-approved drugs

Gene Therapy — Thu, 19 Jan 2012 05:00:00 +0100

Authors: B L Ellis, M L Hirsch, S N Porter, R J Samulski & M H Porteus (Source: Gene Therapy)

[Bronchiolitis obliterans: Outcome in the medium term.]

Anales de Pediatria — Wed, 18 Jan 2012 05:00:00 +0100

CONCLUSIONS: In most cases, fixed air-flow obstruction and lung function stability with low respiratory morbidity were observed. HRCT scan and lung function testing supported the diagnosis. PMID: 22265374 [PubMed - as supplied by publisher] (Source: Anales de Pediatria)

Amelioration of radiation-induced skin injury by adenovirus mediated heme oxygenase-1 (HO-1) overexpression in rats

Radiation Oncology — Tue, 17 Jan 2012 05:00:00 +0100

Conclusions: The present study provides evidences for the protective role of HO-1 in alleviating radiation-induced skin damage in rats, which is helpful for the development of therapy for radiation-induced skin injury. (Source: Radiation Oncology)

RhoA/ROCK-Dependent Moesin Phosphorylation Regulates AGE-induced Endothelial Cellular Response

Cardiovascular Diabetology — Tue, 17 Jan 2012 05:00:00 +0100

Conclusion These results confirm the involvement of RhoA/ROCK pathway and subsequent moesin Thr558 phosphorylation in AGE-mediated endothelial dysfunction. (Source: Cardiovascular Diabetology)

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Determinant role of Phosphoinositide 3‐kinase γ in MCP‐1‐mediated amplification of PDGF‐induced aortic smooth muscle cell migration.

British Journal of Pharmacology — Tue, 17 Jan 2012 05:00:00 +0100

Conclusions and Implications. These results demonstrate that PI3Kγ is essential to MCP‐1‐stimulated aortic SMC migration and amplifies cell migration induced by PDGF by an autocrine/paracrine loop involving MCP‐1 secretion and CCR2 activation and suggest a role of this enzyme in aortic fibroproliferative pathologies. (Source: British Journal of Pharmacology)

Epidemiology of respiratory viral infections in two long-term refugee camps in Kenya, 2007-2010

BMC Infectious Diseases — Tue, 17 Jan 2012 05:00:00 +0100

Background: Refugees are at risk for poor outcomes from acute respiratory infections (ARI) because of overcrowding, suboptimal living conditions, and malnutrition. We implemented surveillance for respiratory viruses in Dadaab and Kakuma refugee camps in Kenya to characterize their role in the epidemiology of ARI among refugees. Methods: From 1 September 2007 through 31 August 2010, we obtained nasopharyngeal (NP) and oropharyngeal (OP) specimens from patients with influenza-like illness (ILI) or severe acute respiratory infections (SARI) and tested them by RT-PCR for adenovirus (AdV), respiratory syncytial virus (RSV), human metapneumovirus (hMPV), parainfluenza viruses (PIV), and influenza A and B viruses. Definitions for ILI and SARI were adapted from those of the World Health Organizati...

Emerging roles for ubiquitin in adenovirus cell entry.

Biology of the Cell — Tue, 17 Jan 2012 05:00:00 +0100

Authors: Marvin SA, Wiethoff CM Abstract Adenovirus relies on numerous interactions between viral and host cell proteins to efficiently enter cells. Undoubtedly, post-translational modifications of host and cellular proteins can impact the efficiency of this cell entry process. Ubiquitylation, once simply thought of as a modification targeting proteins for proteasomal degradation, is now known to regulate protein trafficking within cells, protein-protein interactions, and cell signaling pathways. Accumulating evidence suggests that protein ubiquitylation can influence all stages of the life cycle of other viruses such as cell entry, replication, and egress. Until recently the influence of ubiquitylation has only been documented during adenovirus replication. This review highlights ...

Protective effects of paeoniflorin against cobalt chloride-induced apoptosis of endothelial cells via HIF-1α pathway.

Toxicology in Vitro — Tue, 17 Jan 2012 05:00:00 +0100

This study evaluated the protective effects of paeoniflorin against cobalt chloride (CoCl(2), a hypoxia-mimicking agent)-induced apoptosis of endothelial cells (CRL-1730) and the underlying mechanisms in vitro. Endothelial cells were exposed to CoCl(2) with or without pre-treatment with different concentrations of paeoniflorin. After treated with 0.6mM CoCl(2) for 24h, endothelial cells showed significant decrease in cell viability and increased apoptosis rate, which could be reversed by pre-treatment with paeoniflorin. Similarly, pre-treatment with paeoniflorin could prevent CoCl(2)-induced hypoxia-induced factor-1α (HIF-1α) accumulation and down-regulate the expressions of p53 and Bcl-2/adenovirus E1B 19kDa interacting protein 3 (BNIP3). These findings indicate that paeoniflorin had ef...

A Potent Oncolytic Adenovirus Selectively Blocks the STAT3 Signaling Pathway and Potentiates Cisplatin Antitumor Activity in Ovarian Cancer

Human Gene Therapy — Mon, 16 Jan 2012 16:53:02 +0100

Human Gene Therapy Jan 2012, Vol. 23, No. 1: 32-45. (Source: Human Gene Therapy)

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Novel Mini–Dystrophin Gene Dual Adeno-Associated Virus Vectors Restore Neuronal Nitric Oxide Synthase Expression at the Sarcolemma

Human Gene Therapy — Mon, 16 Jan 2012 16:52:11 +0100

Human Gene Therapy Jan 2012, Vol. 23, No. 1: 98-103. (Source: Human Gene Therapy)

Type 10 adenylyl cyclase mediates mitochondrial Bax translocation and apoptosis of adult rat cardiomyocytes under simulated ischaemia/reperfusion

Cardiovascular Research — Mon, 16 Jan 2012 05:00:00 +0100

Conclusion These results suggest a key role of sAC in SI-induced mitochondrial Bax translocation and activation of the mitochondrial pathway of apoptosis in adult cardiomyocytes. (Source: Cardiovascular Research)

Negative regulation-resistant p53 variant enhances oncolytic adenoviral gene therapy.

Herpes — Mon, 16 Jan 2012 05:00:00 +0100

Authors: Koo T, Choi IK, Kim M, Lee JS, Oh E, Kim J, Yun CO Abstract Intact p53 function is essential for responsiveness to cancer therapy. However, p53 activity is attenuated by the proto-oncoprotein Mdm2, the adenovirus protein E1B-55kD, and the p53 C-terminal domain. To confer resistance to Mdm2, E1B-55kD, and C-terminal negative regulation, we generated a p53 variant (p53VPΔ30) by deleting the N-terminal and C-terminal regions of wild-type (wt) p53 and inserting the transcriptional activation domain of herpes simplex virus VP16 protein. The oncolytic adenovirus vector Ad-mΔ19 expressing p53VPΔ30 (Ad-m19/p53VPΔ30) showed greater cytotoxicity than Ad-mΔ19 expressing wt p53 or other p53 variants in human cancer cell lines. We found that Ad-m∆19/p53VPΔ30 induced apopt...

Protein Kinase C Delta Promotes Adventitial Cell Migration to Neointima by Upregulation of Monocyte Chemoattractant Protein-1 in Smooth Muscle Cells

Journal of Surgical Research — Sat, 14 Jan 2012 22:29:19 +0100

Introduction: Accumulating evidence suggests that adventitial cells directly contribute to neointima formation by migrating into the intima. We have previously reported that gene transfer of Protein kinase C delta(PKC δ) attenuates intimal hyperplasia by inducing apoptosis of smooth muscle cells (SMCs). More recently, we showed that PKCδ mediates expression of monocyte chemoattractant protein-1(MCP-1). in the current study, we tested the hypothesis that PKCδ promotes adventitial cell migration by stimulating SMCs to produce chemokines such as MCP-1. Methods: In vitro migration of isolated adventitial cells was evaluated by chemotaxis assay. Gene transfer to SMCs was achieved by intraluminal perfusion with adenoviruses expressing PKCδ(AdPKCδ) or empty vector (AdNull) following rat caro...

MAPK Pathway Activation in Papillary Thyroid Cancer Contributes to Decreased Interferon-gamma Cellular Growth Inhibition

Journal of Surgical Research — Sat, 14 Jan 2012 22:29:05 +0100

Introduction: Papillary thyroid cancer (PTC) is often associated with one of several non-overlapping mutations within the RAS/RAF signaling pathway. Molecular alterations such as RET/PTC rearrangement or BRAF mutation lead to the activation of the MAPK signaling pathway. Type II interferon (IFN) signaling as seen with IFN gamma in the context of autoimmune thyroiditis has the profound effect of growth inhibition and/or induction of apoptosis in normal thyroid follicular cells. We hypothesize that MAPK pathway activation contributes to the decreased responsiveness of PTC to the effects IFN gamma. Methods: Papillary thyroid TPC-1 (RET/PTC1) and BCPAP (BRAFV600E) cell lines were treated with MEK inhibitors PD98059 (75 mM) and U0126 (10 mM) with and without INF gamma (100 Units/mL) in a time a...

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Transforming Growth Factor- Beta and its Signaling Mediator Smad3 Enhance Cell Survival After Vascular Injury

Journal of Surgical Research — Sat, 14 Jan 2012 22:29:01 +0100

Conclusions: Our data show that TGF-β promotes SMC survival both in vitro and in vivo. This anti-apoptotic effect may well be one of the primary mechanisms through which TGF-β enhances intimal hyperplasia. Knockout and overexpression studies suggest that TGF-β’s inhibitory effect on apoptosis is mediated through the signaling protein Smad3. the correlation with Akt activation suggests that this may be mediated by the Akt-cell survival pathway. (Source: Journal of Surgical Research)

The role of nitric oxide in tendon healing

Journal of Shoulder and Elbow Surgery — Sat, 14 Jan 2012 14:39:41 +0100

Nitric oxide (NO) is a small free radical that is generated by a family of enzymes called the nitric oxide synthases (NOS). There are 3 isoforms of NOS: endothelial NOS (eNOS), brain or neuronal NOS (bNOS), and inducible NOS (iNOS). In experiments performed during the last 20 years, we have shown that NO is induced by all 3 isoforms of NOS after tendon injury and that NOS activity is upregulated in tendinopathy. In normal uninjured tendons, there is very little NOS activity. In injured rat and human tendons, NOS activity was found in healing fibroblasts in a temporal fashion. In animal models, competitive inhibition of NOS resulted in reduced tendon healing, whereas the addition of NO resulted in enhanced tendon healing. In cultured human cells, the addition of NO via chemical means and ad...

Gene therapy.

Herpes — Fri, 13 Jan 2012 11:30:16 +0100

Authors: Gomez-Manzano C, Jiang H, Alonso M, Yung WK, Fueyo J Abstract During the last 10 years, gene therapy for brain tumors has known peaks and valleys. The first attempts to induce therapeutic effect, using retrovirus to transduce the HSV-TK gene and adenovirus to transfer wild-type p53 cDNA, failed significantly to improve the survival of the patients. In both cases, the failure was attributed to vector deficiencies, also termed the 'vector gap'. To address the problem of delivery, investigators have moved from replication-deficient vectors to replication-competent, tumor-selective viruses. These viruses are currently being tested in the clinical setting. In this review, we discuss the progress made with herpes simplex viruses (G207), reoviruses that naturally target Ras pathw...

Marked genomic diversity of Norovirus genogroup I strains in a waterborne outbreak.

Applied and Environmental Microbiology — Fri, 13 Jan 2012 05:00:00 +0100

Authors: Nenonen NP, Hannoun C, Larsson CU, Bergström T Abstract Marked Norovirus (NoV) diversity was detected in patient samples from a large community outbreak of gastroenteritis with waterborne epidemiology affecting approximately 2400 people. NoV was detected in 33 of 50 patient samples examined by group-specific real-time RT-PCR. NoV genotype (G)I strains predominated in 31 patients with mixed GI infections occurring in five of these patients. Sequence-analysis of RNA-dependent polymerase-N/S capsid-coding regions (approx. 900 nt) confirmed dominance of GI strains (n=36). Strains of NoV GI.4 (n=21), and GI.7 (n=9) were identified, but 6 strains required full capsid amino acid analyses (530-550 aa,) before definitive genotyping based on control sequencing of cloned amplicons. ...

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Histone Deacetylase Inhibitors Restore Cell Surface Expression of the Coxsackie Adenovirus Receptor and Enhance CMV Promoter Activity in Castration-Resistant Prostate Cancer Cells

Computational Intelligence and Neuroscience — Thu, 12 Jan 2012 11:11:41 +0100

Adenoviral gene therapy using the death receptor ligand TRAIL as the therapeutic transgene can be safely administered via intraprostatic injection but has not been evaluated for efficacy in patients. Here we investigated the efficacy of adenoviral TRAIL gene therapy in a model of castration resistant prostate cancer and found that intratumoral injections can significantly delay tumor growth but cannot eliminate established lesions. We hypothesized that an underlying cause is inefficient adenoviral delivery. Using the LNCaP progression model of prostate cancer we show that surface CAR expression decreases with increasing tumorigenicity and that castration resistant C4-2b cells were more difficult to transduce with adenovirus than castration sensitive LNCaP cells. Many genes, including CAR, ...

Inflammation and Immune Response of Intra-Articular Serotype 2 Adeno-Associated Virus or Adenovirus Vectors in a Large Animal Model

Computational Intelligence and Neuroscience — Thu, 12 Jan 2012 11:11:41 +0100

Intra-articular gene therapy has potential for the treatment of osteoarthritis and rheumatoid arthritis. To quantify in vitro relative gene transduction, equine chondrocytes and synovial cells were treated with adenovirus vectors (Ad), serotype 2 adeno-associated virus vectors (rAAV2), or self-complementary (sc) AAV2 vectors carrying green fluorescent protein (GFP). Using 6 horses, bilateral metacarpophalangeal joints were injected with Ad, rAAV2, or scAAV2 vectors carrying GFP genes to assess the in vivo joint inflammation and neutralizing antibody (NAb) titer in serum and joint fluid. In vitro, the greater transduction efficiency and sustained gene expression were achieved by scAAV2 compared to rAAV2 in equine chondrocytes and synovial cells. In vivo, AAV2 demonstrated less joint inflamm...

A simple detection system for adenovirus receptor expression using a telomerase-specific replication-competent adenovirus

Gene Therapy — Thu, 12 Jan 2012 05:00:00 +0100

Authors: T Sasaki, H Tazawa, J Hasei, S Osaki, T Kunisada, A Yoshida, Y Hashimoto, S Yano, R Yoshida, S Kagawa, F Uno, Y Urata, T Ozaki & T Fujiwara (Source: Gene Therapy)

Blockade of the Nuclear Factor Kappa B Pathway Prolonged Islet Allograft Survival

Artificial Organs — Thu, 12 Jan 2012 05:00:00 +0100

In this study, the islets were divided into the control group, Ad‐green fluorescent protein, and the adenovirus transfected with inhibitor kappa B group. The proliferation index of peripheral blood mononuclear cells and the islets apoptosis index were examined after mixed lymphocyte‐islet reaction with inverted fluorescence microscopy. Moreover, mRNA expression of inflammatory cytokines was measured by reverse transcription polymerase chain reaction. The islet graft survival time in diabetic rats, insulin in grafts, and cytokine concentrations in the supernatant were determined by immunohistochemistry and enzyme‐linked immunosorbent assay. We found that blocking of NF‐κB activation in β‐cells significantly downregulated inflammatory chemokine production by islets cells in vitro...

Adenovirus-mediated expression of p33ING1b induces apoptosis and inhibits proliferation in gastric adenocarcinoma cells in vitro

Gastric Cancer — Wed, 11 Jan 2012 17:52:12 +0100

Conclusions Down-regulation of p33ING1b might play an important role in the development of gastric adenocarcinoma. Targeted local expression of p33ING1b may offer a promising alternative therapeutic measure for gastric cancer. Content Type Journal ArticleCategory Original articlePages 1-8DOI 10.1007/s10120-011-0123-4Authors Yifei Lv, Department of Gastroenterology, 1st Affiliated Hospital, School of Medicine, Xi’an Jiaotong University, 710061 Xi’an, ChinaBibek Kumar Purbey, Department of Gastroenterology, 1st Affiliated Hospital, School of Medicine, Xi’an Jiaotong University, 710061 Xi’an, ChinaYanhua Huang, Department of Gastroenterology, 1st Affiliated Hospital, School of Medicine, Xi’an Jiaotong University, 710061 Xi’an, ChinaShuang Li, Department of Ga...

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Overexpression of tumor suppressor TSLC1 by a survivin-regulated oncolytic adenovirus significantly inhibits hepatocellular carcinoma growth

Journal of Cancer Research and Clinical Oncology — Wed, 11 Jan 2012 17:51:10 +0100

Conclusion These data suggest that an oncolytic adenovirus expressing TSLC1 is effective and support that SD55-TSLC1 may be a potent antitumoral agent for future clinical trials of liver cancer. Content Type Journal ArticleCategory Original ArticlePages 1-14DOI 10.1007/s00432-011-1138-2Authors Guoqing He, Xinyuan Institute of Medicine and Biotechnology, School of Life Sciences, Zhejiang Sci-Tech University, No. 2 Road Xiasha District, Hangzhou, 310018 ChinaWen Lei, Xinyuan Institute of Medicine and Biotechnology, School of Life Sciences, Zhejiang Sci-Tech University, No. 2 Road Xiasha District, Hangzhou, 310018 ChinaShibin Wang, Xinyuan Institute of Medicine and Biotechnology, School of Life Sciences, Zhejiang Sci-Tech University, No. 2 Road Xiasha District, Hangzhou...

Anti-Cocaine Vaccine Based on Coupling a Cocaine Analog to a Disrupted Adenovirus.

CNS and Neurological Disorders Drug Targets — Tue, 10 Jan 2012 05:00:00 +0100

Authors: Koob G, Hicks M, Wee S, Rosenberg J, De BP, Kaminksy SM, Moreno A, Janda KD, Crystal RG Abstract The challenge in developing an anti-cocaine vaccine is that cocaine is a small molecule, invisible to the immune system. Leveraging the knowledge that adenovirus (Ad) capsid proteins are highly immunogenic in humans, we hypothesized that linking a cocaine hapten to Ad capsid proteins would elicit high-affinity, high-titer antibodies against cocaine, sufficient to sequester systemically administered cocaine and prevent access to the brain, thus suppressing cocaine-induced behaviors. Based on these concepts, we developed dAd5GNE, a disrupted E1ΓE3Γ serotype 5 Ad with GNE, a stable cocaine analog, covalently linked to the Ad capsid proteins. In pre-clinical studies, dAd5GNE evok...

Progress in Gene and Cell Therapy for Cystic Fibrosis Lung Disease.

Current Pharmaceutical Design — Tue, 10 Jan 2012 05:00:00 +0100

Authors: Griesenbach U, Alton EW Abstract Although the development of gene therapy for cystic fibrosis (CF) was high priority for many groups in academia and industry in the first 10 to 15 years after cloning the gene, more recently active research into CF gene therapy is only being performed by a small number of committed, mainly academic, groups. However, despite the warning enthusiasm, which is largely due to the realisation that gene transfer into lungs is more difficult than originally thought and the fact that meaningful clinical trials are expensive and difficult to perform, gene therapy continues to hold promise for the treatment of CF lung disease. Problems related to repeat administration of adenovirus and adeno-associated virus-based vectors led to a focus on non-viral v...

Enveloped virus but not bacteria block IL‐13 responses in human cord blood T‐cells in vitro

Scandinavian Journal of Immunology — Tue, 10 Jan 2012 05:00:00 +0100

Conclusion: These data imply that enveloped virus can deviate Th2 responses in human cord T‐cells. (Source: Scandinavian Journal of Immunology)

Enveloped virus but not bacteria block IL-13 responses in human cord blood T-cells in vitro.

Herpes — Tue, 10 Jan 2012 05:00:00 +0100

Conclusion: These data imply that enveloped virus can deviate Th2 responses in human cord T-cells. PMID: 22229804 [PubMed - as supplied by publisher] (Source: Herpes)

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siRNA-mediated suppression of Japanese encephalitis virus replication in cultured cells and mice

Journal of Antimicrobial Chemotherapy — Tue, 10 Jan 2012 05:00:00 +0100

Conclusions NS5-targeting shRNA (shN8010) had very significant antiviral activity in both cultured cells and the mouse model of JEV infection. (Source: Journal of Antimicrobial Chemotherapy)

Effect of cigarette smoke exposure and structural modifications on the alpha-1 antitrypsin interaction with caspases.

Molecular Medicine — Tue, 10 Jan 2012 05:00:00 +0100

We reported that A1AT protects lung endothelial cells from apoptosis and inhibits caspase-3 activity. It is not clear if cigarette smoking or A1AT mutations alter the caspase-3 inhibitory activity of A1AT and if this serpin alters the function of other caspases. We tested the hypothesis that the caspase-3 inhibitory activity of A1AT is impaired by cigarette smoking and that the A1AT reactive center loop, the key anti-protease domain of the serpin, is required for its interaction with caspase. We examined the caspase-3 inhibitory activity of human A1AT purified from plasma of actively smoking and non-smoking individuals, either affected or unaffected with COPD. We also tested the caspase inhibitory activity of two mutant forms of A1AT, the recombinant human piZZ and the reactive center loop...

Gene Therapy for Leber Congenital Amaurosis Caused by RPE65 Mutations: Safety and Efficacy in 15 Children and Adults Followed Up to 3 Years [Clinical Trial]

Archives of Opthalmology — Mon, 09 Jan 2012 05:00:00 +0100

Conclusions Gene therapy for Leber congenital amaurosis caused by RPE65 mutations is sufficiently safe and substantially efficacious in the extrafoveal retina. There is no benefit and some risk in treating the fovea. No evidence of age-dependent effects was found. Our results point to specific treatment strategies for subsequent phases. Application to Clinical Practice Gene therapy for inherited retinal disease has the potential to become a future part of clinical practice. Trial Registration clinicaltrials.gov Identifier: NCT00481546 (Source: Archives of Opthalmology)

HO‐1 attenuates IL‐1β‐induced cPLA2 expression via a decrease in NADPH oxidase/ROS/AP‐1 activation in human rheumatoid arthritis synovial fibroblasts

Arthritis and Rheumatism — Mon, 09 Jan 2012 05:00:00 +0100

Conclusion.In RASFs, IL‐1β induced cPLA2 expression via activation of p42/p44 MAPK and JNK1/2 leading to phosphorylation of p47phox and ROS production, and AP‐1. The induction of HO‐1 exerted protective effects in the pathogenesis of RA. (Source: Arthritis and Rheumatism)

The transcriptome of the adenovirus infected cell.

Virology — Mon, 09 Jan 2012 05:00:00 +0100

Authors: Zhao H, Dahlö M, Isaksson A, Syvänen AC, Pettersson U Abstract Alternations of cellular gene expression following an adenovirus type 2 infection of human primary cells were studied by using superior sensitive cDNA sequencing. In total, 3791 cellular genes were identified as differentially expressed more than 2-fold. Genes involved in DNA replication, RNA transcription and cell cycle regulation were very abundant among the up-regulated genes. On the other hand, genes involved in various signaling pathways including TGF-β, Rho, G-protein, Map kinase, STAT and NF-κB stood out among the down-regulated genes. Binding sites for E2F, ATF/CREB and AP2 were prevalent in the up-regulated genes, whereas binding sites for SRF and NF-κB were dominant among the down-regulated genes...

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Upregulated p53 expression activates apoptotic pathways in wild-type p53-bearing mesothelioma and enhances cytotoxicity of cisplatin and pemetrexed

Cancer Gene Therapy — Fri, 06 Jan 2012 05:00:00 +0100

Authors: Q Li, K Kawamura, M Yamanaka, S Okamoto, S Yang, S Yamauchi, T Fukamachi, H Kobayashi, Y Tada, Y Takiguchi, K Tatsumi, H Shimada, K Hiroshima & M Tagawa (Source: Cancer Gene Therapy)

Direct and indirect roles for b-catenin in facultative basal progenitor cell differentiation.

American Journal of Physiology. Lung Cellular and Molecular Physiology — Fri, 06 Jan 2012 05:00:00 +0100

DIRECT AND INDIRECT ROLES FOR B-CATENIN IN FACULTATIVE BASAL PROGENITOR CELL DIFFERENTIATION. Am J Physiol Lung Cell Mol Physiol. 2012 Jan 6; Authors: Smith MK, Koch PJ, Reynolds SD Abstract The conducting airway epithelium is maintained and repaired by endogenous progenitor cells. Dysregulated progenitor cell proliferation and differentiation is thought to contribute to epithelial dysplasia in chronic lung disease. Thus, modification of progenitor cell function is an attractive therapeutic goal and one that would be facilitated by knowledge of the molecular pathways that regulate their behavior. We modeled the human tracheobronchial epithelium using primary mouse tracheal epithelial cell cultures that were differentiated by exposure to the air-liquid-interface (ALI). A bas...

Experimental hepatitis C vaccine tested

NHS News Feed — Thu, 05 Jan 2012 16:15:00 +0100

Conclusion This was a small, early-stage human study into a new vaccine against the hepatitis C virus. While such research is required to determine the safety profile of a new therapy, little information on the effectiveness of the vaccine can be gleaned from the study. Phase I clinical trials are designed to determine the optimal dose of a new therapy, and to assess the safety and tolerability of treatments. This study shows that the developed vaccine is well tolerated and safe to use, and the preliminary results indicate that the immune response may be similar to that of people with a natural immunity to the virus. In addition to the small study size and the focus on safety and not effectiveness, there are other practical limitations to the study that should be considered before it is co...

Chimp Viruses Look Promising For Vaccines

AAAS — Thu, 05 Jan 2012 14:24:16 +0100

Science Translational Medicine: Chimp Viruses Could Aid Vaccine Development for Hepatitis C Vaccines developed using chimpanzee adenoviruses trigger immune protection against hepatitis C, two research teams report in Science Translational Medicine. (Source: AAAS)

AAV8 vector expressing IL24 efficiently suppresses tumor growth mediated by specific mechanisms in MLL/AF4-positive ALL model mice

Blood — Thu, 05 Jan 2012 05:00:00 +0100

We examined the effects of adeno-associated virus type 8 (AAV8) vector-mediated muscle-directed systemic gene therapy in MLL/AF4-positive ALL using IL24. In a series of in vitro studies, we examined the effects of AAV8-IL24–transduced C2C12 cell-conditioned medium. We also examined the effects of AAV8-IL24 in MLL/AF4 transgenic mice. The results revealed the effects of AAV8-IL24 in MLL/AF4-positive ALL both in vitro and in vivo. With regard to the mechanism of therapy using AAV8-IL24 in MLL/AF4-positive ALL, we demonstrated the antiangiogenicity and effects on the ER stress pathway and unreported pathways through inhibition of S100A6 and HOXA9, which is specific to MLL/AF4-positive ALL. Inhibition of S100A6 by IL24 was dependent on TNF-α and induced acetylation of p53 followed ...

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Adeno-Associated Virus-Mediated Brain Delivery of 5-Lipoxygenase modulates the AD-like phenotype of APP mice

Molecular Neurodegeneration — Thu, 05 Jan 2012 05:00:00 +0100

Conclusions: These data demonstrate that neuronal 5LO plays a functional role in the pathogenesis of AD-like amyloidotic phenotype by modulating the gamma-secretase pathway. They support the hypothesis that this enzyme is a novel therapeutic target for the treatment and prevention of AD. (Source: Molecular Neurodegeneration)

Antitumor effects of bladder cancer-specific adenovirus carrying E1A-androgen receptor in bladder cancer

Gene Therapy — Thu, 05 Jan 2012 05:00:00 +0100

Authors: Z Zhai, Z Wang, S Fu, J Lu, F Wang, R Li, H Zhang, S Li, Z Hou, H Wang & R Rodriguez (Source: Gene Therapy)

Early detection and visualization of human adenovirus serotype 5-viral vectors carrying foot-and-mouth disease virus or luciferase transgenes in cell lines and bovine tissues.

Vaccine — Thu, 05 Jan 2012 05:00:00 +0100

Authors: Montiel N, Smoliga G, Arzt J Abstract Recombinant replication-defective human adenovirus type 5 (Ad5) vaccines containing capsid-coding regions from foot-and-mouth disease virus (FMDV) have been demonstrated to induce effective immune responses and provide homologous protective immunity against FMDV in cattle. However, basic mechanisms of Ad5-FMDV vaccine function including virus tropism, transgene expression, and antigen presentation, remain incompletely understood. The current study characterized the dynamics of Ad5 viral vector (Ad5-FMDV-A24 and Ad5-luciferase) infection in cell lines and early post-inoculation vector-host interactions in cattle. Adenovirus dissemination was described utilizing novel rPCR, rRT-PCR, luminometry, and immunomicroscopy techniques. In vitro ...

Vaccine protection against acquisition of neutralization-resistant SIV challenges in rhesus monkeys

Nature AOP — Wed, 04 Jan 2012 05:00:00 +0100

Authors: Dan H. Barouch, Jinyan Liu, Hualin Li, Lori F. Maxfield, Peter Abbink, Diana M. Lynch, M. Justin Iampietro, Adam SanMiguel, Michael S. Seaman, Guido Ferrari, Donald N. Forthal, Ilnour Ourmanov, Vanessa M. Hirsch, Angela Carville, Keith G. Mansfield, Donald Stablein, Maria G. Pau, Hanneke Schuitemaker, Jerald C. Sadoff, Erik M. Billings, Mangala Rao, Merlin L. Robb, Jerome H. Kim, Mary A. Marovich, Jaap Goudsmit & Nelson L. Michael Preclinical studies of human immunodeficiency virus type 1 (HIV-1) vaccine candidates have typically shown post-infection virological control, but protection against acquisition of infection has previously only been reported against neutralization-sensitive virus challenges. Here we demonstrate vaccine protection against acquisition of fully heterolo...

Oncolytic virotherapy in veterinary medicine: current status and future prospects for canine patients

Journal of Translational Medicine — Wed, 04 Jan 2012 05:00:00 +0100

Oncolytic viruses refer to those that are able to eliminate malignancies by direct targeting and lysis of cancer cells, leaving non-cancerous tissues unharmed. Several oncolytic viruses including adenovirus strains, canine distemper virus and vaccinia virus strains have been used for canine cancer therapy in preclinical studies. However, in contrast to human studies, clinical trials with oncolytic viruses for canine cancer patients have not been reported. An 'ideal' virus has yet to be identified. This review is focused on the prospective use of oncolytic viruses in the treatment of canine tumors - a knowledge that will undoubtedly contribute to the development of oncolytic viral agents for canine cancer therapy in the future. (Source: Journal of Translational Medicine)

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Translocation of calcium-permeable TRPV2 channel to the podosome: Its role in the regulation of podosome assembly.

Cell Calcium — Wed, 04 Jan 2012 05:00:00 +0100

Authors: Nagasawa M, Kojima I Abstract The present study was conducted to investigate localization and function of TRPV2 channel in a mouse macrophage cell line, TtT/M87. We infected an adenovirus vector encoding TRPV2 tagged with c-Myc in the extracellular domain. Immunoreactivity of c-Myc epitope exposed to the cell surface formed a ring structure, which was colocalized with markers of the podosome, namely β-integrin, paxillin and Pyk2. The ring structure was also observed in TRPV2-GFP-expressing cells using total internal reflection fluorescent microscopy. Addition of formyl-Met-Leu-Phe (fMLP) increased the number of podosome and increased the intensity of the TRPV2 signal associated with the podosome. Measurement of subplasmalenmal free calcium concentration ([Ca(2+)](pm)) rev...

Vaccine protection against acquisition of neutralization-resistant SIV challenges in rhesus monkeys

Nature — Wed, 04 Jan 2012 05:00:00 +0100

Authors: Dan H. Barouch, Jinyan Liu, Hualin Li, Lori F. Maxfield, Peter Abbink, Diana M. Lynch, M. Justin Iampietro, Adam SanMiguel, Michael S. Seaman, Guido Ferrari, Donald N. Forthal, Ilnour Ourmanov, Vanessa M. Hirsch, Angela Carville, Keith G. Mansfield, Donald Stablein, Maria G. Pau, Hanneke Schuitemaker, Jerald C. Sadoff, Erik A. Billings, Mangala Rao, Merlin L. Robb, Jerome H. Kim, Mary A. Marovich, Jaap Goudsmit & Nelson L. Michael Preclinical studies of human immunodeficiency virus type 1 (HIV-1) vaccine candidates have typically shown post-infection virological control, but protection against acquisition of infection has previously only been reported against neutralization-sensitive virus challenges. Here we demonstrate vaccine protection against acquisition of fully het...

The impact of pandemic influenza A (H1N1) 2009 on the circulation of respiratory viruses 2009–2011

Influenza and Other Respiratory Viruses — Sun, 01 Jan 2012 05:00:00 +0100

Please cite this paper as: Mak et al. (2012) The impact of pandemic influenza A (H1N1) 2009 on the circulation of respiratory viruses 2009–2011 DOI: 10.1111/j.1750‐2659.2011.00323.x.Surveillance of respiratory viruses has been conducted for many years at the public health laboratory in Hong Kong. With the occurrence of pandemic influenza A (H1N1) 2009, we observed a change in the seasonality of influenza activity with a seemingly corresponding change in the activity of respiratory syncytial virus, parainfluenza virus, and adenovirus during 2009–2011. This phenomenon could most likely be explained by virus interference. (Source: Influenza and Other Respiratory Viruses)

Adenovirus-Mediated Gene Transfection in the Isolated Lymphatic Vessels

Springer protocols feed by Molecular Medicine — Sun, 01 Jan 2012 05:00:00 +0100

The authors describe technical details of experimental protocol of gene transfection in isolated rat mesenteric lymphatic vessels (MLVs). Authors also refer to the recent publication in Microcirculation, which provides wide set of experimental evidences obtained from confocal microscopic imaging and isolated vessels functional tests, which confirmed a successful achievement of the following goals. (1) Optimization of the experimental conditions to maintain the isolated “normal” rat mesenteric vessels in culture for sufficiently long periods of time to permit effective knockdown or overexpression of selected proteins/genes. (2) Development of the effective transfection protocols for lymphatic muscle and/or endothelial cells in intact isolated rat MLVs without nonspecific impairm...

In this issue.

European Journal of Immunology — Sun, 01 Jan 2012 05:00:00 +0100

Authors: Abstract COVER IMAGE: The cover shows a histological analysis of an ear section from a C57BL/6 mouse that was first sensitised with 2,4-dinitrofluorobenzene on the belly and then challenged 4 days later with 2,4-dinitrofluorobenzene on the ear. Haematoxylin and eosin staining shows massive skin infiltration by mononuclear cells and granulocytes 24 h after challenge. The image is from Rouzaire et al. (pp. 80-88) in which the authors show that NK cells and T cells induce different types of inflammatory reactions in the skin during recall responses to haptens; of note, NK cell-mediated pathogenesis does not rely on cellular infiltrate. A 'MÉNAGE À TROIS' IN THE GERMINAL CENTRE INVOLVING HUMAN ΓΔ T CELLS: Vγ9/Vδ2 T cells comprise a minor subset of unconventional T cells...

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Baculovirus‐mediated vascular endothelial growth factor‐DΔNΔC gene transfer induces angiogenesis in rabbit skeletal muscle

The Journal of Gene Medicine — Sun, 01 Jan 2012 05:00:00 +0100

ConclusionsWe show the first evidence of biologically significant baculoviral gene transfer in skeletal muscle of NZW rabbits using VEGF‐DΔNΔC as a therapeutic transgene. Copyright © 2012 John Wiley & Sons, Ltd. (Source: The Journal of Gene Medicine)

Combination of a MDR1-targeted replicative adenovirus and chemotherapy for the therapy of pretreated ovarian cancer

Journal of Cancer Research and Clinical Oncology — Sat, 31 Dec 2011 06:37:12 +0100

Conclusion These preclinical data suggest that a fiber-modified adenovirus vector under the control of the MDR1 promoter represents a promising treatment strategy for platinum-pretreated ovarian cancer as a single agent or in combination with conventional anticancer drugs. Content Type Journal ArticleCategory Original ArticlePages 1-8DOI 10.1007/s00432-011-1135-5Authors Daniel T. Rein, Department of Obstetrics and Gynecology, University of Düsseldorf Medical Center, Moorenstrasse 5, 40225 Düsseldorf, GermanyAnne Volkmer, Department of Obstetrics and Gynecology, University of Düsseldorf Medical Center, Moorenstrasse 5, 40225 Düsseldorf, GermanyGerd Bauerschmitz, Department of Obstetrics and Gynecology, University of Düsseldorf Medical Center, Moorenstrasse 5, 402...

In this issue

European Journal of Immunology — Fri, 30 Dec 2011 23:53:32 +0100

AbstractCover imageThe cover shows a histological analysis of an ear section from a C57BL/6 mouse that was first sensitised with 2,4‐dinitrofluorobenzene on the belly and then challenged 4 days later with 2,4‐dinitrofluorobenzene on the ear. Haematoxylin and eosin staining shows massive skin infiltration by mononuclear cells and granulocytes 24 h after challenge. The image is from Rouzaire et al. (pp. 80–88) in which the authors show that NK cells and T cells induce different types of inflammatory reactions in the skin during recall responses to haptens; of note, NK cell‐mediated pathogenesis does not rely on cellular infiltrate.A ‘ménage à trois’ in the germinal centre involving human γδ T cellsVγ9/Vδ2 T cells comprise a minor subset of unconventional T cells in the bloo...

Viruses Zapped With Plasma Treatment Before They Can Attack Cells

Health News from Medical News Today — Fri, 30 Dec 2011 08:00:00 +0100

Adenoviruses can cause respiratory, eye, and intestinal tract infections, and, like other viruses, must hijack the cellular machinery of infected organisms in order to produce proteins and their own viral spawn. Now an international research team made up of scientists from Chinese and Australian universities has found a way to disrupt the hijacking process by using plasma to damage the viruses in the laboratory environment, before they come into contact with host cells... (Source: Health News from Medical News Today)

Influenza‐like illness surveillance on the California‐Mexico border, 2004–2009

Influenza and Other Respiratory Viruses — Fri, 30 Dec 2011 05:00:00 +0100

Conclusions The US‐Mexico border is one of the busiest in the world, with a large number of daily crossings. Due to its traffic, this area is an ideal location for surveillance sites. We identified a pathogen in 36% of the specimens tested, with influenza A the most common pathogen. A number of other viral and bacterial respiratory pathogens were identified. An understanding of the incidence of respiratory pathogens in border populations is useful for development of regional vaccination and disease prevention responses. (Source: Influenza and Other Respiratory Viruses)

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Interferon regulatory factor 3 plays an anti-inflammatory role in microglia by activating the PI3K/Akt pathway

Journal of Neuroinflammation — Fri, 30 Dec 2011 05:00:00 +0100

Conclusions: Our results show a novel anti-inflammatory role for the PI3K/Akt signaling pathway in microglia. They further suggest that IRF3 gene therapy could facilitate the microglial phenotype switch from proinflammatory ("M1-like") to anti-inflammatory and immunomodulatory ("M2-like"), in part, by augmenting the level of pAkt. (Source: Journal of Neuroinflammation)

Human adenovirus-specific T cells modulate HIV-specific T cell responses to an Ad5-vectored HIV-1 vaccine

Journal of Clinical Investigation — Thu, 29 Dec 2011 11:17:32 +0100

Recombinant viruses hold promise as vectors for vaccines to prevent infectious diseases with significant global health impacts. One of their major limitations is that preexisting anti-vector neutralizing antibodies can reduce T cell responses to the insert antigens; however, the impact of vector-specific cellular immunity on subsequent insert-specific T cell responses has not been assessed in humans. Here, we have identified and compared adenovirus-specific and HIV-specific T cell responses in subjects participating in two HIV-1 vaccine trials using a vaccine vectored by adenovirus serotype 5 (Ad5). Higher frequencies of pre-immunization adenovirus-specific CD4+ T cells were associated with substantially decreased magnitude of HIV-specific CD4+ T cell responses and decreased breadth of HIV...

Rare serotype adenoviral vectors for HIV vaccine development

Journal of Clinical Investigation — Thu, 29 Dec 2011 11:17:32 +0100

Human adenoviral vectors are being developed for use in candidate vaccines for HIV-1 and other pathogens. However, this approach suffered a setback when an HIV-1 vaccine using an adenovirus type 5 (Ad5) vector failed to reduce, and might even have increased, the rate of HIV infection in men who were uncircumcised and who had preexisting antibodies specific for Ad5. This increased interest in the evaluation of serologically distinct adenoviral vectors. In this issue of the JCI, Frahm and coworkers report evidence that preexisting cellular immune responses directed toward Ad5 reduce the immunogenicity of antigens expressed in Ad5-vectored vaccines and have cross-reacting potential with non-Ad5 adenoviral vectors. The implications of this observation need to be carefully evaluated in future c...

Vascular Bioactivation of Nitroglycerin Is Catalyzed by Cytosolic Aldehyde Dehydrogenase-2.

Circulation Research — Thu, 29 Dec 2011 05:00:00 +0100

Conclusions:The data indicate that vascular bioactivation of GTN is catalyzed by cytosolic ALDH2. Mitochondrial GTN metabolism may contribute to oxidative stress-related adverse effects of nitrate therapy and the development of nitrate tolerance. PMID: 22207712 [PubMed - as supplied by publisher] (Source: Circulation Research)

Evaluation of BMP‐2 gene‐activated muscle grafts for cranial defect repair

Journal of Orthopaedic Research — Wed, 28 Dec 2011 20:50:39 +0100

This study confirms the in vivo osteogenic properties of genetically modified muscle and suggests novel strategies for healing bone. © 2011 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res (Source: Journal of Orthopaedic Research)

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Immune Response May Render HIV Vaccine IneffectiveImmune Response May Render HIV Vaccine Ineffective

Medscape Today Headlines — Tue, 27 Dec 2011 22:34:54 +0100

Patients' immune response to adenovirus-based vaccine components may explain the lack of benefit observed in some vaccine trials. Medscape Medical News (Source: Medscape Today Headlines)

Cellular FLICE-inhibitory protein protects against cardiac remodelling after myocardial infarction

Basic Research in Cardiology — Tue, 27 Dec 2011 17:04:23 +0100

In conclusion, our results indicate that cFLIP protects against the development of post-infarction cardiac remodelling. Thus, cFLIP gene delivery shows promise as a clinically powerful and novel therapeutic strategy for the treatment of heart failure after MI. Content Type Journal ArticleCategory Original ContributionPages 1-21DOI 10.1007/s00395-011-0239-zAuthors Jinfeng Xiao, Department of Cardiology, Renmin Hospital of Wuhan University, Jiefang Road 238, Wuhan, 430060 People’s Republic of ChinaMark Moon, Division of Cardiology, Heart and Stroke/Richard Lewar Centre of Excellence, University Health Network, University of Toronto, Toronto, ON M5S 3E2, CanadaLing Yan, Department of Cardiology, Renmin Hospital of Wuhan University, Jiefang Road 238, Wuhan, 430060 People’s Republi...

In vitro characterization of the activity of PF-05095808 a novel biological agent for Hepatitis C Virus therapy.

Antimicrobial Agents and Chemotherapy — Tue, 27 Dec 2011 05:00:00 +0100

Authors: Lavender H, Brady K, Burden F, Delpuech-Adams O, Denise H, Palmer A, Perkins H, Savic B, Scott S, Smith-Burchnell C, Troke P, Wright JF, Suhy D, Corbau R Abstract PF-05095808 is a novel biological agent for chronic Hepatitis C Virus (HCV) therapy. It comprises a recombinant Adeno-associated virus (AAV) DNA vector packaged into an AAV serotype 8 capsid. The vector directs expression of 3 short hairpin (sh) RNAs targeted to conserved regions of the HCV genome. These shRNAs are processed by the host cell into the small interfering RNAs which mediate sequence specific cleavage of target regions. For small molecule inhibitors the key screens needed to assess in vitro activity are well defined, we developed new assays to assess this RNA interference agent and so understand its t...

Adenovirus ANT2 shRNA effectively induces apoptosis and enhances chemosensitivity by the down-regulation of ABCG2 in breast cancer stem-like cells.

exp Mol Med — Mon, 26 Dec 2011 05:00:00 +0100

In this study, we determined whether or not ANT2 suppression could also be effective in inducing cell death of breast cancer stem-like cells. A sub-population (SP; CD44+/CD24-) of breast cancer cells has been reported to have stem/progenitor cell properties. We utilized the adeno-ANT2 shRNA virus to inhibit ANT2 expression and then observed the treatment effect in a SP of breast cancer cell line. In this study, MCF7, MDA-MB-231 cells, and breast epithelial cells (MCF10A) mesenchymally-transdifferentiated through E-cadherin knockdown were used. ANT2 expression was high in both stem-like cells and non-stem-like cells of MCF7 and MDA-MB-231 cells, and was induced and up-regulated by mesenchymal transdifferentiation in MCF10A cells (MCF10AEMT). Knockdown of ANT2 by adeno-shRNA virus efficientl...

Serological evaluation of relationship between viral pathogens (BHV-1, BVDV, BRSV, PI-3V, and Adeno3) and dairy calf pneumonia by indirect ELISA

Tropical Animal Health and Production — Sat, 24 Dec 2011 06:41:46 +0100

In this study, viral pathogens associated with nine outbreaks of naturally occurring dairy calf pneumonia in Mashhad area of Khorasan Razavi province from September 2008 to May 2009 were assessed. Five diseased calves from each farm were chosen for examination. Acute and convalescent serum samples were taken from calves with signs of respiratory disease. Sera were analyzed for antibodies to bovine viral diarrhea virus (BVDV), bovine herpesvirus type 1 (BHV-1), bovine respiratory syncytial virus (BRSV), parainfluenza virus type 3 (PI-3V), and bovine adenovirus-3 (BAV-3) by indirect ELISA kits. Among 42 serum samples collected at sample 1, seroprevalence values for viruses BHV-1, BVDV, BRSV, PI-3V, and BAV-3 were 61.9% (26), 57.1% (24), 64.2% (27), 90% (38), and 61.9% (26), respectivel...

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Adenovirus-Mediated Gene Transfer of Transforming Growth Factor β1 to the Renal Glomeruli Leads to Proteinuria.

Am J Pathol — Sat, 24 Dec 2011 05:00:00 +0100

In this study, we used an adenovirus vector to transfer active TGFβ1 to the glomeruli of rat kidneys. Transient TGFβ1 overexpression induced significant proteinuria, podocyte foot process effacement, nephrin down-regulation, and nephrinuria. The expression of synaptopodin was also significantly down-regulated by TGFβ1. Increased glomerular expression of Snail, suggestive of an in vivo dedifferentiation process, was associated with a loss of podocyte epithelial markers. The expression of angiopoietin-1 and angiopoietin-2 was significantly increased in TGFβ1-transfected glomeruli, and TGFβ1 increased the expression of the angiopoietin receptor, Tie2, in podocyte cell culture. TGFβ1 down-regulated nephrin and synaptopodin expression in podocytes in cell culture; this effect was reversed...

Evolution of oncolytic adenovirus for cancer treatment.

Advanced Drug Delivery Reviews — Sat, 24 Dec 2011 05:00:00 +0100

Authors: Choi JW, Lee JS, Kim SW, Yun CO Abstract Oncolytic adenovirus (Ad) has been used in cancer gene therapy largely due to its ability to selectively infect and replicate in tumor cells. However, because the oncolytic antitumor activity is insufficient to effectively eliminate tumors, various strategies have been devised to improve the therapeutic efficacy. Single-vector Ads "armed" with short hairpin RNA, cytokines, or matrix-modulating proteins have been developed. Two clear advantages are viral amplification of the therapeutic gene, and the additive effects of oncolytic and therapeutic gene-mediated antitumor activities. To develop systemically injectable Ad carriers, strategies to modify the Ad surface with polymers, liposomes, or nanoparticles have been shown to extend ci...

Effects of antioxidant gene therapy on retinal neurons and oxidative stress in a model of retinal ischemia/reperfusion.

Free Radical Biology and Medicine — Sat, 24 Dec 2011 05:00:00 +0100

Authors: Liu Y, Tang L, Chen B Abstract Retinal ischemia/reperfusion (I/R) results in neuronal death and generation of reactive oxygen species. The aim of this study was to investigate the neuroprotective effect of manganese superoxide dismutase (SOD2) on retinal ganglion cells (RGCs) in an I/R-induced retinal injury model. One eye of each Wistar rat was pretreated with recombinant adeno-associated virus containing the SOD2 gene (AAV-SOD2) or recombinant AAV containing the GFP gene (AAV-GFP) by intravitreal injection 21days before initiation of I/R injury. Retinal I/R injury was induced by elevating intraocular pressure for 1h, and reperfusion was established immediately afterward. The number of RGCs and the inner plexiform layer (IPL) thickness were measured by Fluorogold retrogra...

Room-temperature, atmospheric plasma needle reduces adenovirus gene expression in HEK 293A host cells

Applied Physics Letters — Fri, 23 Dec 2011 14:18:37 +0100

Z. Xiong, X. Lu, Y. Cao, Q. Ning, K. Ostrikov et al. Room-temperature, atmospheric-pressure plasma needle treatment is used to effectively minimize the adenovirus (AdV) infectivity as quantified by the dramatic reduction of its gene expression in HEK 293A primary human embryonic kidney cells studied by green fluorescent protein imaging. The AdV titer ... [Appl. Phys. Lett. 99, 253703 (2011)] published Tue Dec 20, 2011. (Source: Applied Physics Letters)

Viral-bacterial co-infection in Australian Indigenous children with acute otitis media.

Rural Remote Health — Thu, 22 Dec 2011 21:36:02 +0100

CONCLUSION: This study confirms a positive association between nasopharyngeal bacterial load and clinical ear state, exacerbated by respiratory viruses, in Indigenous children. HAdV was independently associated with acute ear states. PMID: 21649905 [PubMed - indexed for MEDLINE] (Source: Rural Remote Health)

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[Newsdesk] Research brief

The Lancet Infectious Diseases — Thu, 22 Dec 2011 11:07:41 +0100

To date, no effective vaccines against HIV have been developed and, although some people produce broadly neutralising antibodies in response to HIV infection, whether conventional vaccination can elicit the production of similar antibodies is unclear. Now a study describes an alternative approach to HIV prophylaxis—vectored immunoprophylaxis (VIP). VIP uses an adeno-associated virus vector to engineer the secretion of existing broadly neutralising antibodies into the circulation. Intramuscular VIP injection protects humanised mice from challenge with high doses of replication competent HIV. (Source: The Lancet Infectious Diseases)

Isolation, identification, and complete genome sequence of a bovine adenovirus type 3 from cattle in China

Virology Journal — Thu, 22 Dec 2011 05:00:00 +0100

Conclusions: This is the first study to report the isolation and molecular characterization of BAV-3 from cattle in China. The phylogenetic analysis performed in this study supported the use of the DNA binding protein gene of adenovirus as an appropriate subgenomic target for the classification of different genuses of the family Adenoviridae on the molecular basis. Meanwhile, a large-scale pathogen and serological epidemiological investigations for BVA-3 infection might be carried out in cattle in China. This report will be a good beginning for further studies on BAV-3 in China. (Source: Virology Journal)

Simultaneous detection of infectious human echoviruses and adenoviruses by an in situ nuclease-resistant molecular beacon-based assay.

Applied and Environmental Microbiology — Thu, 22 Dec 2011 05:00:00 +0100

Authors: Dunams D, Sarkar P, Chen W, Yates MV Abstract A multiplex methodology using two nuclease-resistant molecular beacons that target specific genomic regions of adenovirus 2 and echovirus 17 during simultaneous infection in A549 cells is presented. Using fluorescence microscopy, visualization enteroviral and adenoviral replication was possible within 3 hours post-infection. PMID: 22194298 [PubMed - as supplied by publisher] (Source: Applied and Environmental Microbiology)

Psoriasin (S100A7) increases the expression of ROS and VEGF and acts through RAGE to promote endothelial cell proliferation

Breast Cancer Research and Treatment — Wed, 21 Dec 2011 20:04:56 +0100

Abstract Psoriasin (S100A7), originally identified in psoriasis, is a calcium-binding protein belonging to the multigenic S100 family. In high-grade ductal carcinoma in situ, psoriasin was identified as one of the most abundant transcripts. We have previously shown that psoriasin was induced by reactive oxygen species (ROS). Moreover, the downregulation of psoriasin by short hairpin RNA (shRNA) led to the reduced expression of vascular endothelial growth factor (VEGF) and inhibited tumor growth in vivo. The aim of the present study was to investigate whether psoriasin could have direct effects on endothelial cells. In this study we demonstrated that psoriasin increased VEGF expression in mammary epithelial cells. The treatment of endothelial cells with recombinant psoriasi...

Suppression of protein phosphatase 2A activity enhances Ad5/F35 adenovirus transduction efficiency in normal human B lymphocytes and in Raji cells.

Journal of Immunological Methods — Wed, 21 Dec 2011 05:00:00 +0100

Authors: Cayer MP, Samson M, Bertrand C, Dumont N, Drouin M, Jung D Abstract Investigation of the molecular processes which control the development and function of lymphocytes is essential for our understanding of humoral immunity, as well as lymphocyte associated pathogenesis. Adenovirus-mediated gene transfer provided a powerful tool to investigate these processes. We have previously demonstrated that adenoviral vector Ad5/F35 transduces plasma cell lines at a higher efficiency than primary B cells, owing to differences in intracellular trafficking. Given that phosphatases are effectors of intracellular trafficking, here we have analyzed the effects of a panel of phosphatase inhibitors on Ad5/F35 transduction efficiency in B lymphocytes in the present study. FACS analysis was con...

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RORα‐induced activation of AMP‐activated protein kinase results in attenuation of hepatic steatosis

Hepatology — Tue, 20 Dec 2011 05:00:00 +0100

Conclusion: We found that RORα induced the activation of AMPK and the inhibition of the lipogenic function of LXRα, which may be key phenomena that provide beneficial effects of RORα against hepatic steatosis. (HEPATOLOGY 2011.) (Source: Hepatology)

Early infection and spread of a conditionally replicating adenovirus under conditions of plaque formation.

Virology — Tue, 20 Dec 2011 05:00:00 +0100

Authors: Hofacre A, Wodarz D, Komarova NL, Fan H Abstract Conditionally-replicating adenoviruses (CRAds) and other oncolytic viruses replicate selectively in tumor cells, presenting a potential cancer treatment approach. To optimize application of these viruses, understanding of early spread of these viruses in target cells is important. Here we used a recombinant adenovirus expressing enhanced jellyfish green fluorescent protein (EGFP) in place of the EIA and EIB genes (AdEGFPuci). Infection of susceptible cells (AD-293) under plaque formation conditions (MOI<<1) on gridded culture dishes and daily monitoring allowed visualization of initially infected cells, as well as spread to neighboring cells. We determined key parameters of early infection, including the rate and effic...

Transduction, Tropism, and Biodistribution of AAV Vectors in the Lacrimal Gland [Cornea]

Investigative Ophthalmology — Tue, 20 Dec 2011 05:00:00 +0100

Conclusions. LG gene delivery by AAV vectors appears to be both safe and well tolerated. The choice of vector influences both the overall transduction activity, as well as the spread of vector to other organs. This work supports the use of AAV-mediated gene therapy for dry eye. (Source: Investigative Ophthalmology)

AAV-Mediated Gene Transfer of Human X-Linked Inhibitor of Apoptosis Protects against Oxidative Cell Death in Human RPE Cells [Retinal Cell Biology]

Investigative Ophthalmology — Tue, 20 Dec 2011 05:00:00 +0100

Conclusions. Overexpression of human XIAP protects ARPE-19 cells against H2O2-induced oxidative cell death by acting downstream on the apoptotic pathway. XIAP gene therapy using AAV may provide a means of reducing the effect of oxidative stress to RPE cells in age-related macular degeneration. (Source: Investigative Ophthalmology)

Dendritic cells transfected with PD-L1 recombinant adenovirus induces T cell suppression and long-term acceptance of allograft transplantation.

Cellular Immunology — Sun, 18 Dec 2011 12:18:03 +0100

Authors: Peng W, Ran B, Ma Y, Huang X, Chang Q, Wang X Abstract The purpose of this study is to assess the potential of dendritic cells transfected with PD-L1 recombinant adenovirus induces CD8+ T cell suppression and kidney allograft tolerance. To prove it, DCs transfected with PD-L1 recombinant adenovirus (DC/Ad-PD-L1) were transferred into the MHC-mismatched rat kidney transplants. After kidney transplantation, the mixed lymphocyte reaction (MLR) assay and kidney function were analyzed. The results demonstrated that after administration of DC/Ad-PD-L1, the proliferation, cytokines secretion and activation marker expression of CD8+ T cells were suppressed. In addition, DC/Ad-PD-L1 could improve kidney function and survival of transplants. The findings suggested that DC/Ad-PD-L1 c...

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Generation and Hepatic Differentiation of Human iPS Cells.

Cell Research — Sun, 18 Dec 2011 06:00:13 +0100

Authors: Ishikawa T, Hagiwara K, Ochiya T Abstract A method for the generation of human induced pluripotent stem (iPS) cells was established. This method employs adenovirus carrying the ecotropic retrovirus receptor mCAT1 and Moloney murine leukemia virus (MMLV)-based retroviral vectors carrying the four transcription factors POU5F1 (OCT3/4), KLF4, SOX2, and MYC (c-Myc) (Masaki H & Ishikawa T Stem Cell Res 1:105-15, 2007). The differentiation of human iPS cells into hepatic cells was performed by a stepwise protocol (Song Z et al. Cell Res 19:1233-42, 2009). These cells have potential as patient-specific in vitro models for studying disease etiology and could be used in drug discovery programs tailored to deal with genetic variations in drug efficacy and toxicity. PMID: 221...

Performance evaluation of detecting adenovirus by using rapid diagnostic kits among Japanese people

Journal of Infection and Chemotherapy — Fri, 16 Dec 2011 06:54:31 +0100

This study evaluated the diagnostic performance of detecting adenovirus by rapid diagnostic kits among Japanese people. A meta-analysis was conducted to pool the sensitivity, specificity, positive and negative likelihood ratios, and diagnostic odds ratio of immunochromatography methods and latex agglutination tests; enzyme-linked immunosorbent assay tests had already been evaluated in another meta-analysis, and no other diagnostic kits have been appropriately studied. Immunochromatography methods were shown to have sufficiently high diagnostic power, regardless of whether conjunctiva or throat swabs, or stool specimens were sampled, based upon the area under the curve (0.961–0.991); this was significantly higher than enzyme-linked immunosorbent assay tests when sampling conjunctiva...

PASK Mutations and Insulin Secretion Regulation [Metabolism]

Journal of Biological Chemistry — Fri, 16 Dec 2011 05:00:00 +0100

PAS kinase (PASK) is a glucose-regulated protein kinase involved in the control of pancreatic islet hormone release and insulin sensitivity. We aimed here to identify mutations in the PASK gene that may be associated with young-onset diabetes in humans. We screened 18 diabetic probands with unelucidated maturity-onset diabetes of the young (MODY). We identified two rare nonsynonymous mutations in the PASK gene (p.L1051V and p.G1117E), each of which was found in a single MODY family. Wild type or mutant PASKs were expressed in HEK 293 cells. Kinase activity of the affinity-purified proteins was assayed as autophosphorylation at amino acid Thr307 or against an Ugp1p-derived peptide. Whereas the PASK p.G1117E mutant displayed a ∼25% increase with respect to wild type PASK in the extent of a...

IGF-I increases the expression of fibronectin by Nox4-dependent Akt phosphorylation in renal tubular epithelial cells

AJP: Cell Physiology — Fri, 16 Dec 2011 05:00:00 +0100

Extracellular matrix accumulation contributes to the progression of chronic kidney disease. Many growth factors including insulin-like growth factor-I (IGF-I) enhance matrix protein accumulation. Proximal tubular epithelial cells (PTCs) synthesize matrix proteins. NADPH oxidases are major sources of reactive oxygen species (ROS), important signaling molecules that mediate biological responses in a variety of cells and tissue. We investigated the mechanism by which IGF-I regulates fibronectin accumulation in PTCs and the role of a potential redox-dependent signaling pathway. IGF-I induces an increase in NADPH-dependent superoxide generation, enhances the release of hydrogen peroxide, and increases the expression of NADPH oxidase 4 (Nox4) in PTCs. IGF-I also stimulates phosphorylation of Akt...

Skeletal muscle regeneration is delayed by reduction in Xin expression: consequence of impaired satellite cell activation?

AJP: Cell Physiology — Fri, 16 Dec 2011 05:00:00 +0100

Xin is a striated muscle-specific actin-binding protein whose mRNA expression has been observed in damaged skeletal muscle. Here we demonstrate increased Xin protein expression early postinjury (≤12 h) and localization primarily to the periphery of damaged myofibers. At 1 day postinjury, Xin is colocalized with MyoD, confirming expression in activated satellite cells (SCs). By 5 days postinjury, Xin is evident in newly regenerated myofibers, with a return to preinjury levels by 14 days of regeneration. To determine whether the increased Xin expression is functionally relevant, tibialis anterior muscles of wild-type mice were infected with Xin-short hairpin RNA (shRNA) adenovirus, whereas the contralateral tibialis anterior received control adenovirus (Control). Four days postinfection, ...

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KCNE2 protein is more abundant in ventricles than in atria and can accelerate hERG protein degradation in a phosphorylation-dependent manner.

American Journal of Physiology. Heart and Circulatory Physiology — Fri, 16 Dec 2011 05:00:00 +0100

Authors: Zhang M, Wang Y, Jiang M, Zankov DP, Chowdhury S, Kasirajan V, Tseng GN Abstract KCNE2 functions as an auxiliary subunit in voltage-gated K and HCN channels in the heart. Genetic variations in KCNE2 have been linked to long QT syndrome (LQT6). The underlying mechanisms are not entirely clear. One of the issues is whether KCNE2 protein is expressed in ventricles. We use adenovirus-mediated genetic manipulations of adult cardiac myocytes to validate two antibodies (termed Ab1 and Ab2) for their ability to detect native KCNE2 in the heart. Ab1 faithfully detects native KCNE2 proteins in spontaneously hypertensive rat (SHR) and guinea pig hearts. In both cases, KCNE2 protein is more abundant in ventricles than in atria. In both ventricular and atrial myocytes, KCNE2 protein is...

Overexpression of angiopoietin-2 impairs myocardial angiogenesis and exacerbates cardiac fibrosis in the diabetic db/db mouse model.

American Journal of Physiology. Heart and Circulatory Physiology — Fri, 16 Dec 2011 05:00:00 +0100

This study investigates the potential role of Ang-2 in myocardial angiogenesis and fibrosis formation in the diabetic db/db mouse. Diabetic db/db mice received intra-myocardial administration of either adenovirus Ang-2 (Ad-CMV-Ang-2) or Ad-β-gal. The levels of Tie-2, VEGF, caspase-3, Wnt7b, fibroblast specific protein-1 (FSP-1), adhesion molecules (ICAM-1 and VCAM-1) expression were measured. Apoptosis, capillary density, and cardiac fibrosis were also analyzed in the db/db mouse hearts. Overexpression of Ang-2 suppressed Tie-2 and VEGF expression in db/db mouse hearts together with significant upregulation of Wnt7b expression. Overexpression of Ang-2 also sensitizes ICAM-1 and VCAM-1 expression in db/db mouse hearts. Immunohistochemical analysis revealed that overexpression of Ang-2 resu...

Tetradecanoylphorbol-13-acetate (TPA) significantly increases AAV2/5 transduction of human neuronal cells in vitro.

Experimental Eye Research — Fri, 16 Dec 2011 05:00:00 +0100

In this study we show that transduction of the human neuroblastoma cell line SH-SY5Y with recombinant AAV2/5 expressing GFP is well tolerated. Furthermore, we explore the mechanism whereby exposure to retinoic acid (RA) and the phorbol ester 12-O-Tetradecanoylphorbol-13- acetate (TPA) can induce this cell line to differentiate into a stable population of human neurons, with significantly increased levels of AAV2/5 transduction. These observations may be helpful for assessing AAV2/5 vectors in vitro, particularly where it is necessary to generate pre-clinical data for clinical trials of gene therapy to the human central nervous system. PMID: 22197749 [PubMed - as supplied by publisher] (Source: Experimental Eye Research)

A Single Sublingual Dose of an Adenovirus-Based Vaccine Protects against Lethal Ebola Challenge in Mice and Guinea Pigs

Molecular Pharmaceutics — Thu, 15 Dec 2011 18:58:42 +0100

Molecular PharmaceuticsDOI: 10.1021/mp200392g (Source: Molecular Pharmaceutics)

Effect of glucagon‐like peptide‐1 gene expression on graft function in mouse islet transplantation

Transplant International — Thu, 15 Dec 2011 05:00:00 +0100

In conclusion, delivery of the GLP‐1 gene to islets enhanced islet cell survival during the early post‐transplant period, and preserved islet mass and functions over time in the transplants. (Source: Transplant International)

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Adeno-Associated Virus 2 Infection Requires Endocytosis through the CLIC/GEEC Pathway.

Cell Host and Microbe — Thu, 15 Dec 2011 05:00:00 +0100

Authors: Nonnenmacher M, Weber T Abstract Adeno-associated viruses (AAVs) are nonpathogenic, nonenveloped, single-stranded DNA viruses in development as gene therapy vectors. AAV internalization was postulated to proceed via a dynamin-dependent endocytic mechanism. Revisiting this, we find that infectious endocytosis of the prototypical AAV, AAV2, is independent of clathrin, caveolin, and dynamin. AAV2 infection is sensitive to EIPA, a fluid-phase uptake inhibitor, but is unaffected by Rac1 mutants or other macropinocytosis inhibitors. In contrast, AAV2 infection requires actin cytoskeleton remodeling and membrane cholesterol and is sensitive to inhibition of Cdc42, Arf1, and GRAF1, factors known to be involved in the formation of clathrin-independent carriers (CLIC). AAV2 virion...

Gene Transfer Restores Clotting Factor Level in Hemophilia BGene Transfer Restores Clotting Factor Level in Hemophilia B

Medscape Today Headlines — Tue, 13 Dec 2011 17:17:40 +0100

Adeno-associated virus serotype 8 carries factor IX gene into 6 patients, enabling 4 to stop regular prophylaxis. Medscape Medical News (Source: Medscape Today Headlines)

Integration of adenovirus thymidine kinase suicide-gene therapy with surgery and radiation therapy for malignant glioma

Future Oncology — Tue, 13 Dec 2011 15:56:24 +0100

Future Oncology , January 2012, Vol. 8, No. 1, Pages 17-20. (Source: Future Oncology)

The development of Chinese specific human cytomegalovirus polyepitope recombinant vaccine.

Antiviral Research — Tue, 13 Dec 2011 05:00:00 +0100

Authors: Zhao P, Ma DX, Yu S, Xue FZ, Zhu WW, Shao N, Zhang JR, Ji CY Abstract Human cytomegalovirus (HCMV) infection is a major cause of morbidity in the recipients of organ transplants and in the congenitally infected infants. HCMV vaccine has emerged as an effective approach to prevent HCMV infection particularly for the development of multiple viral antigens vaccination and human leukocyte antigen (HLA)-restricted polyepitope technology. As the Chinese population makes up more than one fifth of the population worldwide, it is important to develop HCMV vaccines more specific for the Chinese population by targeting Chinese-restricted HLA alleles and antigens. In the present study, we designed a novel chimeric polyepitope vaccine based on the replication-deficient adenovirus Ad5F3...

Glutamate Transporter GLT-1 Upregulation Attenuates Visceral Nociception and Hyperalgesia via Spinal Mechanisms Not Related to Anti-Inflammatory or Probiotic Effects

Clinical and Developmental Immunology — Mon, 12 Dec 2011 23:53:11 +0100

Visceral pain is the most common reason for physician visits in US. Glutamate is the major excitatory neurotransmitter and mediates visceral nociceptive neuro-transmission and hypersensitivity. Removal of extracellular glutamate is predominantly mediated by glial glutamate transporter-1 (GLT-1). The pharmacological approach to up-regulate GLT-1 by 1 week administration of ceftriaxone (CTX) has been successful to mitigate visceral nociception. The present study shows that intrathecal delivery of selective GLT-1 antagonist dihydrokainate reversed CTX-blunted visceral nociceptive response, suggesting a spinal site of action. The role of GLT-1 up-regulation in animal models of colitis was studied. CTX treatment reversed TNBS-induced visceral hypersensitivity. In addition, CTX treatment initiat...

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Gene therapy used to treat haemophilia

NHS News Feed — Mon, 12 Dec 2011 17:50:00 +0100

Conclusion Patients with haemophilia B have defects in the gene normally used to produce the important blood-clotting protein FIX. Patients with severe haemophilia B have less than 1% of normal levels of functional FIX protein. The exciting finding of this study suggests that gene therapy might be a safe and effective way to increase the level of FIX in haemophilia B patients’ bodies, in some cases removing the need for FIX injections altogether. In this study, prolonged production of functional FIX protein was observed after injection with a single dose of virus carrying a normal version of the FIX gene, and few side effects occurred. However, this was an early-stage, relatively short, small study with only six participants and no comparison group. As the researchers themselves conclude...

Suppression of endogenous PPARγ increases vulnerability to methamphetamine-induced injury in mouse nigrostriatal dopaminergic pathway

Psychopharmacology — Mon, 12 Dec 2011 17:12:04 +0100

Conclusion A deficiency in PPARγ increases vulnerability to high doses of methamphetamine. Endogenous PPARγ may play an important role in reducing methamphetamine toxicity in vivo. Content Type Journal ArticleCategory Original InvestigationPages 1-14DOI 10.1007/s00213-011-2595-7Authors Seong-Jin Yu, National Institute on Drug Abuse, IRP, Neural Protection and Regeneration Section, 251 Bayview Boulevard, 06-721A, Baltimore, MD 21224, USAMikko Airavaara, National Institute on Drug Abuse, IRP, Neural Protection and Regeneration Section, 251 Bayview Boulevard, 06-721A, Baltimore, MD 21224, USAHui Shen, National Institute on Drug Abuse, IRP, Neural Protection and Regeneration Section, 251 Bayview Boulevard, 06-721A, Baltimore, MD 21224, USAJenny Chou, National Institute...

HIV-infection resistance in PMBC-derived dendritic cells modified with recombinant virus

Archives of Virology — Sat, 10 Dec 2011 16:56:41 +0100

This study aimed to identify the characteristics of recombinant-adenovirus-modified PBMC-derived dendritic cells and their resistance to HIV-1 infection by integrating the CCR5∆32, CCR5siRNA, HIV-1 pol and HIV-1 int genes into a recombinant adenovirus vector using the AdEasy system. Dendritic cells (DCs) were isolated from human PBMCs from blood of healthy donors. The expression of CCR5∆32, CCR5, CXCR4 and HIV-1 p24 in PBMCs or modified cells was measured by western blot, p24 expression in cell lysates was measured by ELISA, and HIV-1 entry was measured by β-galactosidase assay. Furthermore, T-cell immunity induced by the recombinant adenovirus was measured by ELISPOT assay. After the cells were modified by Ad-R5∆32siRNA, the expression of CCR5∆32 increased, w...

Adenovirus-Associated Virus Vector–Mediated Gene Transfer in Hemophilia B

New England Journal of Medicine — Sat, 10 Dec 2011 16:00:04 +0100

New England Journal of Medicine, Volume 0, Issue 0, Ahead of Print. (Source: New England Journal of Medicine)

The antitumor effects of adenoviral-mediated, intratumoral delivery of interleukin 23 require endogenous IL-12

Cancer Gene Therapy — Fri, 09 Dec 2011 05:00:00 +0100

Authors: J Reay, A Gambotto & P D Robbins (Source: Cancer Gene Therapy)

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Regulation of Dopamine Level in the Nigrostriatal Projection [Molecular Bases of Disease]

Journal of Biological Chemistry — Fri, 09 Dec 2011 05:00:00 +0100

The tyrosine hydroxylase (TH; EC 1.14.16.2) is a rate-limiting enzyme in the dopamine synthesis and important for the central dopaminergic system, which controls voluntary movements and reward-dependent behaviors. Here, to further explore the regulatory mechanism of dopamine levels by TH in adult mouse brains, we employed a genetic method to inactivate the Th gene in the nigrostriatal projection using the Cre-loxP system. Stereotaxic injection of adeno-associated virus expressing Cre recombinase (AAV-Cre) into the substantia nigra pars compacta (SNc), where dopaminergic cell bodies locate, specifically inactivated the Th gene. Whereas the number of TH-expressing cells decreased to less than 40% in the SNc 2 weeks after the AAV-Cre injection, the striatal TH protein level decreased to 75%, ...

Frontotemporal lobar degeneration related proteins induce only subtle memory-related deficits when bilaterally overexpressed in the dorsal hippocampus.

Experimental Neurology — Fri, 09 Dec 2011 05:00:00 +0100

Authors: Dayton RD, Wang DB, Cain CD, Schrott LM, Ramirez JJ, King MA, Klein RL Abstract Frontotemporal lobar degeneration (FTLD) is a neurodegenerative disease that involves cognitive decline and dementia. To model the hippocampal neurodegeneration and memory-related behavioral impairment that occurs in FTLD and other tau and TDP-43 proteinopathy diseases, we used an adeno-associated virus serotype 9 (AAV9) vector to induce bilateral expression of either microtubule-associated protein tau or transactive response DNA binding protein 43kDa (TDP-43) in adult rat dorsal hippocampus. Human wild-type forms of tau or TDP-43 were expressed. The vectors/doses were designed for moderate expression levels within neurons. Rats were evaluated for acquisition and retention in the Morris water t...

pUNISHER: a high-level expression cassette for use with recombinant viral vectors for rapid and long term in vivo neuronal expression in the CNS

Journal of Neurophysiology — Thu, 08 Dec 2011 05:00:00 +0100

In this study, we tested various cis elements to optimize transgene expression at transcriptional, posttranscriptional, and posttranslational levels and combined them together to create the high-level neuronal transgene expression cassette pUNISHER. Using a second-generation adenoviral vector system in combination with the pUNISHER cassette, we characterized its rate of onset of detectable expression and levels of expression compared with a neurospecific expression cassette driven by the 470-bp human synapsin promoter in vitro and in vivo. Our results demonstrate in primary neurons that the pUNISHER cassette, in a recombinant adenovirus type 5 background, led to a faster rate of onset of detectable transgene expression and higher level of transgene expression. More importantly, this casset...

Identification of the heparin binding site on adeno-associated virus serotype 3B (AAV-3B).

Virology — Thu, 08 Dec 2011 05:00:00 +0100

Authors: Lerch TF, Chapman MS Abstract Adeno-associated virus is a promising vector for gene therapy. In the current study, the binding site on AAV serotype 3B for the heparan sulfate proteoglycan (HSPG) receptor has been characterized. X-ray diffraction identified a disaccharide binding site at the most positively charged region on the virus surface. The contributions of basic amino acids at this and other sites were characterized using site-directed mutagenesis. Both heparin and cell binding are correlated to positive charge at the disaccharide binding site, and transduction is significantly decreased in AAV-3B vectors mutated at this site to reduce heparin binding. While the receptor attachment sites of AAV-3B and AAV-2 are both in the general vicinity of the viral spikes, the e...

Mineralized Tissue Formation by Bone Morphogenetic Protein-7–transfected Pulp Stem Cells

Journal of Endodontics — Thu, 08 Dec 2011 05:00:00 +0100

Conclusions: Our data suggest that adenovirus-mediated BMP-7 expression can induce odontogenic differentiation of human DPSCs and show effectively mineralized tissue formation in vivo, which may provide support for gene therapy candidate of BMP-7 in dental tissue engineering. (Source: Journal of Endodontics)

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Plasma-Based Treatment Goes Viral

Health News from Medical News Today — Wed, 07 Dec 2011 08:00:00 +0100

Life-threatening viruses such as HIV, SARS, hepatitis and influenza, could soon be combatted in an unusual manner as researchers have demonstrated the effectiveness of plasma for inactivating and preventing the replication of adenoviruses. When exposed to plasma - the fourth state of matter in addition to solids, liquids and gases - for a period of just 240 seconds, it was found that only one in a million viruses could still replicate - practically all were inactivated... (Source: Health News from Medical News Today)

Synergistic Tumor Suppression by Adenovirus-Mediated Inhibitor of Growth 4 and Interleukin-24 Gene Cotransfer in Hepatocarcinoma Cells

Cancer Biotherapy and Radiopharmaceuticals — Tue, 06 Dec 2011 21:26:10 +0100

Cancer Biotherapy & Radiopharmaceuticals Dec 2011, Vol. 26, No. 6: 681-695. (Source: Cancer Biotherapy and Radiopharmaceuticals)

Plasma-based treatment goes viral

EurekAlert! - Medicine and Health — Mon, 05 Dec 2011 05:00:00 +0100

(Institute of Physics) Life-threatening viruses such as HIV, SARS, hepatitis and influenza, could soon be combated in an unusual manner as researchers have demonstrated the effectiveness of plasma for inactivating and preventing the replication of adenoviruses. (Source: EurekAlert! - Medicine and Health)

Angiotensin-converting enzyme 2 overexpression improves central nitric oxide-mediated sympathetic outflow in chronic heart failure

AJP: Heart and Circulatory Physiology — Mon, 05 Dec 2011 05:00:00 +0100

Angiotensin (ANG)-converting enzyme (ACE)2 in brain regions such as the paraventricular nucleus (PVN) controlling cardiovascular function may be involved in the regulation of sympathetic outflow in chronic heart failure (CHF). The purpose of this study was to determine if ACE2 plays a role in the central regulation of sympathetic outflow by regulating neuronal nitric oxide (NO) synthase (nNOS) in the PVN. We investigated ACE2 and nNOS expression within the PVN of rats with CHF. We then determined the effects of ACE2 gene transfer in the PVN on the contribution of NO-mediated sympathoinhibition in rats with CHF. The results showed that there were decreased expressions for ACE2, the ANG-(1–7) receptor, and nNOS within the PVN of rats with CHF. After the application of adenovirus vector...

Molecular typing of adenoviruses in pediatric respiratory infections in Buenos Aires, Argentina (1999–2010)

Journal of Clinical Virology — Mon, 05 Dec 2011 05:00:00 +0100

Abstract: Background: The human adenovirus (HAdV) types most commonly found in respiratory samples belong to HAdV species C (HAdV-C1, -C2, -C5, and -C6) and to HAdV species B (HAdV-B3 and -B7). Several studies in South America have shown the association between severe respiratory infections and subspecies B1.Objectives: The aim of this study was to identify the adenovirus types associated with acute lower respiratory tract infections in children, found as single or coinfections, throughout a 12-year period.Study design: All samples that tested positive for adenovirus by immunofluorescence assay from January 1999 to December 2010 were typed by evaluating a set of four viral genes (E1A, VA, hexon and fiber). Quantitative PCRs for HAdV-B and HAdV-C species were performed to compare the viral ...

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7B2 Over- and Underexpression and Peptide Precursor Cleavage [Cell Biology]

Journal of Biological Chemistry — Fri, 02 Dec 2011 05:00:00 +0100

The small neuroendocrine protein 7B2 is required for the production of active prohormone convertase 2 (PC2), an enzyme involved in the synthesis of peptide hormones, such as glucagon and proopiomelanocortin-derived α-melanocyte-stimulating hormone. However, whether 7B2 can dynamically modulate peptide production through regulation of PC2 activity remains unclear. Infection of the pancreatic alpha cell line α-TC6 with 7B2-encoding adenovirus efficiently increased production of glucagon, whereas siRNA-mediated knockdown of 7B2 significantly decreased stored glucagon. Furthermore, rescue of 7B2 expression in primary pituitary cultures prepared from 7B2 null mice restored melanocyte-stimulating hormone production, substantiating the role of 7B2 as a regulatory factor in peptide biosynthesis....

Survival of host-associated Bacteroidales cells and their relationship with Enterococcus spp., Campylobacter jejuni, Salmonella Typhimurium and Adenovirus in freshwater microcosms as measured by PMA-qPCR.

Applied and Environmental Microbiology — Fri, 02 Dec 2011 05:00:00 +0100

Authors: Bae S, Wuertz S Abstract The ideal host-associated genetic fecal marker would be capable of predicting the presence of specific pathogens of concern. Flow-through freshwater microcosms containing mixed feces and inocula of the pathogens Campylobacter jejuni, Salmonella Typhimurium and Adenovirus were placed at ambient temperature in the presence and absence of diurnal sunlight. The total Enterococcus DNA increased during the early periods (23 h) under sunlight exposure, even though cultivable Enterococcus and DNA in intact cells, as measured by propidium monoazide (PMA), decreased with first-order kinetics during the entire period. We found a significant difference in the decay of host-associated Bacteroidales cells between sunlight exposure and dark conditions (p-value &l...

PVN adenovirus-siRNA injections silencing either NOX2 or NOX4 attenuate aldosterone/NaCl-induced hypertension in mice.

American Journal of Physiology. Heart and Circulatory Physiology — Fri, 02 Dec 2011 05:00:00 +0100

Authors: Xue B, Beltz TG, Johnson RF, Guo F, Hay M, Johnson AK Abstract Mineralocorticoid excess increases superoxide production by activating NADPH oxidase, and intracerebroventricular infusions of NADPH oxidase inhibitors attenuate aldosterone (Aldo)/salt-induced hypertension. It has been hypothesized that increased reactive oxygen species (ROS) in the brain may be a key mechanism in the development of hypertension. The present study investigated the brain regional specificity of NADPH oxidase and the role of NOX2 and NOX4 NADPH oxidase subunits in the hypothalamic paraventricular nucleus (PVN) in Aldo/salt-induced hypertension. PVN injections of adenoviral vectors expressing siRNA targeting NOX2 (AdsiRNA-NOX2) or NOX4 (AdsiRNA-NOX4) mRNAs were used to knock down NOX2 and NOX4 pr...

Effect of Hypoxia-Inducible Factor-1α Gene Therapy on Walking Performance in Patients With Intermittent Claudication

Journal of Vascular Surgery — Thu, 01 Dec 2011 05:00:00 +0100

Gene therapy with intramuscular administration of Ad2/HIF-1α/VP16 is not effective treatment for intermittent claudication. Induction of angiogenesis of lower extremity arteries via protein, gene based, or cellular therapy may result in new blood vessel formation and improved blood flow in patients with intermittent claudication. Hypoxia- inducible factor 1α (HIF-1α) is a transcriptional regulatory factor with important roles in cellular response to changes in oxygen tension (Semenza GL. Science 2007; 318:62-4). HIF-1α exerts control on multiple genes providing adaptive responses to hypoxia at the cellular level. HIF-1α/V16 is hybrid transcription factor comprised of a truncated HIF-1α sequence fused to a herpes simplex virus (VP16) transactivator. A previous phase 1 trial of patien...

Effect of Silencing VDR Gene in Kidney on Renal Epithelial Calcium Transporter Proteins and Urinary Calcium Excretion in Genetic Hypercalciuric Stone-forming Rats

Urology — Thu, 01 Dec 2011 05:00:00 +0100

Conclusion: Our findings suggest that VDR knockdown in the kidney can upregulate the expression of transient receptor potential vanilloid receptor subtype 5 in GHS rats. However, VDR depletion results in an increase in urine calcium excretion. The role of VDR in the hypercalciuric formation needs to be elucidated further. (Source: Urology)

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Recombinant adenovirus carrying the hepatocyte nuclear factor‐1alpha gene inhibits hepatocellular carcinoma xenograft growth in mice

Hepatology — Thu, 01 Dec 2011 05:00:00 +0100

Conclusion: These results suggest that the potent inhibitive effect of HNF1α on HCC is attained by inducing the differentiation of hepatoma cells into mature hepatocytes and G2/M arrest. HNF1α might represent a novel, promising therapeutic agent for human HCC treatment. Our findings also encourage the evaluation of differentiation therapy for tumors of organs other than liver using their corresponding differentiation‐determining transcription factor. (HEPATOLOGY 2011) (Source: Hepatology)

Corrections: Intrahepatic injection of adenovirus reduces inflammation and increases gene transfer and therapeutic effect in mice

Hepatology — Thu, 01 Dec 2011 05:00:00 +0100

(Source: Hepatology)

Prevalence of viral infections and hemorrhagic cystitis in hematopoietic stem cell transplant recipients.

Thu, 01 Dec 2011 05:00:00 +0100

Conclusions: Detection of single and multiple infections of BK virus, adenovirus, and cytomegalovirus in blood and/or urine samples of hematopoietic stem cell transplant recipients, in combination with 1 or more inducing factors of hemorrhagic cystitis were enforced on the important role these risk factors play in the cause of hemorrhagic cystitis. PMID: 22142049 [PubMed - in process] (Source: Experimental and Clinical Transplantation : official journal of the Middle East Society for Organ Transplantation)

IKKβ‐induced inflammation impacts the kinetics but not the magnitude of the immune response to a viral vector

European Journal of Immunology — Thu, 01 Dec 2011 05:00:00 +0100

In this study, we sought to determine whether activation of the pro‐inflammatory inhibitor of κB kinase βIKKβ canonical NF‐κB pathway promoted vaccine‐induced immune responses. An adenovirus expressing constitutively‐activated IKKβ (AdIKK) induced robust DC maturation and high expression of key cytokines compared to a control virus. In vivo, AdIKK triggered rapid inflammation after pulmonary infection, increased leukocyte entry into draining LNs, and enhanced early antibody and T‐cell responses. Notably, AdIKK did not influence the overall magnitude of the adaptive immune response. These results indicate that induction of inflammation by IKKβ/NF‐κB in this setting impacts the kinetics but not the magnitude of adaptive immune responses. These findings therefore help defin...