J Allergy Clin Immunol
September 2010
These parameters were developed by the Joint Task Force on Practice Parameters, representing the American Academy of Allergy, Asthma & Immunology (AAAAI); the American College of Allergy, Asthma & Immunology (ACAAI); and the Joint Council of Allergy, Asthma and Immunology. The AAAAI and the ACAAI have jointly accepted responsibility for establishing "The Diagnosis and Management of Anaphylaxis Practice Parameter: 2010 Update." This is a complete and comprehensive document at the current time.
View Article and Find Full Text PDFThe Snail transcription factor is a repressor and a master regulator of epithelial-mesenchymal transition (EMT) events in normal embryonic development and during tumor metastases. Snail directly regulates genes affecting cell adhesion, motility, and polarity. Invasive tumor cells express high levels of Snail, which is a marker for aggressive disease and poor prognosis.
View Article and Find Full Text PDFThe Epstein-Barr virus immediate-early protein (Zta) plays an essential role in viral lytic activation and pathogenesis. Zta is a basic zipper (b-Zip) domain-containing protein that binds multiple sites in the viral origin of lytic replication (OriLyt) and is required for lytic-cycle DNA replication. We present evidence that Zta binds to a sequence-specific, imperfect DNA hairpin formed by an inverted repeat within the upstream essential element (UEE) of OriLyt.
View Article and Find Full Text PDFCurr Allergy Asthma Rep
January 2010
Vasomotor rhinitis is a common disorder that is seen routinely in allergy practice. It affects millions of Americans and results in significant morbidity. The pathophysiology of this complex heterogeneous disorder is unknown, but we are making advances in this regard.
View Article and Find Full Text PDFBackground: Epstein-Barr Virus (EBV) latent infection is associated with several human malignancies and is a causal agent of lymphoproliferative diseases during immunosuppression. While inhibitors of herpesvirus DNA polymerases, like gancyclovir, reduce EBV lytic cycle infection, these treatments have limited efficacy for treating latent infection. EBNA1 is an EBV-encoded DNA-binding protein required for viral genome maintenance during latent infection.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
March 2010
Animals capable of regenerating multiple tissue types, organs, and appendages after injury are common yet sporadic and include some sponge, hydra, planarian, and salamander (i.e., newt and axolotl) species, but notably such regenerative capacity is rare in mammals.
View Article and Find Full Text PDFPoly(ADP-ribose) polymerase (PARP) is an abundant, chromatin-associated, NAD-dependent enzyme that functions in multiple chromosomal processes, including DNA replication and chromatin remodeling. The Epstein-Barr virus (EBV) origin of plasmid replication (OriP) is a dynamic genetic element that confers stable episome maintenance, DNA replication initiation, and chromatin organization functions. OriP function depends on the EBV-encoded origin binding protein EBNA1.
View Article and Find Full Text PDFThe Epstein-Barr virus (EBV) origin of plasmid replication (OriP) is required for episome stability during latent infection. Telomere repeat factor 2 (TRF2) binds directly to OriP and facilitates DNA replication and plasmid maintenance. Recent studies have found that TRF2 interacts with the DNA damage checkpoint protein Chk2.
View Article and Find Full Text PDFKaposi's sarcoma-associated herpesvirus (KSHV) encodes a cluster of 12 microRNAs (miRNAs) that are processed from a transcript that is embedded within the major latency control region. We have generated a deletion mutation that eliminates 10 of the 12 viral miRNAs from the KSHV bacmid by using recombineering methods. The KSHV miRNA deletion mutant (BAC36 DeltamiR) behaved similarly to wild-type (wt) BAC36 in viral production, latency gene transcription, and viral DNA copy number in 293 and dermal microvascular endothelial cells (DMVECs).
View Article and Find Full Text PDFHerpesviruses are a complex family of dsDNA viruses that are a major cause of human disease. All family members share highly related viral replication proteins, such as DNA polymerase, ssDNA-binding proteins and processivity factors. Consequently, it is generally thought that lytic replication occurs through a common and conserved mechanism.
View Article and Find Full Text PDFSelf-reinforcing negative feedback loops are commonly observed in biological systems. RNA-mediated negative feedback loops have been described in the formation of heterochromatin at centromeres in fission yeast and the inactive X chromosome in mammalian cells. The telomere repeat-containing RNA (TERRA) has also been implicated in the formation of telomeric heterochromatin through a self-reinforcing negative feedback loop.
View Article and Find Full Text PDFThe gammaherpesviruses are a subclass of the herpesvirus family that establish stable latent infections in proliferating lymphoid and epithelial cells. The latent genomes are maintained as multicopy chromatinized episomes that replicate in synchrony with the cellular genome. Importantly, most of the episomes do not integrate into the host chromosome.
View Article and Find Full Text PDFHistamine is a central nervous system (CNS) neurotransmitter. It acts in the brain via three receptors, H(1), H(2), and H(3). It is a mediator of "wakefulness" and its activity is necessary to maintain wakefulness, alertness, and reaction time.
View Article and Find Full Text PDFAlthough antihistamines have been in common use for treatment of allergic diseases including rhinitis for >60 years and topical therapy of the respiratory tract has been common for centuries, it is only in the past few years that topical intranasal antihistamine therapy has been widely used for treatment of allergic rhinitis. Much research has been done over the past several years showing broad anti-inflammatory effects of these medications, involving many different pathways. Effects have been shown on mediators including histamine, leukotrienes, platelet-activating factor, and substance P, as well as on cytokines, adhesion molecules, and chemokines involved in chemotaxis.
View Article and Find Full Text PDFTelomere-repeat-encoding RNA (referred to as TERRA) has been identified as a potential component of yeast and mammalian telomeres. We show here that TERRA RNA interacts with several telomere-associated proteins, including telomere repeat factors 1 (TRF1) and 2 (TRF2), subunits of the origin recognition complex (ORC), heterochromatin protein 1 (HP1), histone H3 trimethyl K9 (H3 K9me3), and members of the DNA-damage-sensing pathway. siRNA depletion of TERRA caused an increase in telomere dysfunction-induced foci, aberrations in metaphase telomeres, and a loss of histone H3 K9me3 and ORC at telomere repeat DNA.
View Article and Find Full Text PDFLatent infection by Epstein-Barr virus (EBV) requires both replication and maintenance of the viral genome. EBV nuclear antigen 1 (EBNA1) is a virus-encoded protein that is critical for the replication and maintenance of the genome during latency in proliferating cells. We have previously demonstrated that EBNA1 recruits the cellular origin recognition complex (ORC) through an RNA-dependent interaction with EBNA1 linking region 1 (LR1) and LR2.
View Article and Find Full Text PDFCellular topoisomerases and helicases are thought to play an essential role in herpesvirus replication and gene expression and are considered to be potential targets for antiviral therapies. Topoisomerase I (Topo I) and Topo II inhibitors can selectively inhibit Epstein-Barr virus (EBV) lytic cycle DNA replication. We found that the Topo I inhibitor camptothecin and, to a lesser extent, the Topo II inhibitor etoposide are potent inhibitors of the transcription and replication function of the EBV-encoded immediate-early protein Zta (also referred to as ZEBRA, EB1, and BZLF1).
View Article and Find Full Text PDFUsing a mouse model, Enard et al. (2009) show that the human form of the FOXP2 gene increases synaptic plasticity and dendrite connectivity in the basal ganglia. These results partly explain the enhanced capability of cortico-basal ganglia circuits in the human brain that regulate critical aspects of language, cognition, and motor control.
View Article and Find Full Text PDFVasomotor rhinitis (VMR) is a common but poorly understood disorder of which there are two major subgroups: VMR(w/t), triggered by weather/temperature and VMR(ir), triggered by airborne irritants. No specific biological pathways or specific treatments for VMR(w/t) or VMR(ir) have been identified. However, intranasal corticosteroids (INSs) are effective in treating many forms of nonallergic rhinitis that include these conditions.
View Article and Find Full Text PDFAnn Allergy Asthma Immunol
April 2009
Objectives: To ascertain the rate of occurrence of unintentional injections from epinephrine autoinjectors used in the first aid treatment of anaphylaxis and to provide information about the resulting needle stick injuries.
Data Sources: A systematic review was performed. The MEDLINE, Scirus, CINAHL, ISI Web of Science, and Google Scholar databases were searched by title and abstract to identify reports of unintentional injections from epinephrine autoinjectors published in peer-reviewed journals.
Kaposi's sarcoma-associated herpesvirus (KSHV) latency is characterized by the highly regulated transcription of a few viral genes essential for genome maintenance and host cell survival. A major latency control region has been identified upstream of the divergent promoters for the multicistronic transcripts encoding LANA (ORF73), vCyclin (ORF72), and vFLIP (ORF71) and for the complementary strand transcript encoding K14 and vGPCR (ORF74). Previous studies have shown that this major latency control region is occupied by the cellular chromatin boundary factor CTCF and chromosome structural maintenance proteins SMC1, SMC3, and RAD21, which comprise the cohesin complex.
View Article and Find Full Text PDFHydroxyurea (HU) is a chemotherapeutic agent commonly used for various malignancies and hematological disorders, including chronic myelogenous leukemia and sickle cell anemia. We show here that chronic, low-level treatment with HU induces a variety of defects in telomere replication and maintenance. HU treatment preferentially decreased the rate of telomere DNA synthesis and altered the cell cycle timing of telomere replication.
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