Abstract：
:Herpes simplex virus and varicella-zoster virus have been treated for more that half a century using nucleoside analogues. However, there is still an unmet clinical need for improved herpes antivirals. The successful compounds, acyclovir; penciclovir and their orally bioavailable prodrugs valaciclovir and famciclovir, ultimately block virus replication by inhibiting virus-specific DNA-polymerase. The helicase-primase (HP) complex offers a distinctly different target for specific inhibition of virus DNA synthesis. This review describes the synthetic programmes that have already led to two HP-inhibitors (HPI) that have commenced clinical trials in man. One of these (known as AIC 316) continues in clinical development to date. The specificity of HPI is reflected by the ability to select drug-resistant mutants. The role of HP-antiviral resistance will be considered and how the study of cross--resistance among mutants already shows subtle differences between compounds in this respect. The impact of resistance on the drug development in the clinic will also be considered. Finally, herpesvirus latency remains as the most important barrier to a therapeutic cure. Whether or not helicase primase inhibitors alone or in combination with nucleoside analogues can impact on this elusive goal remains to be seen.
journal_name
Adv Exp Med Bioljournal_title
Advances in experimental medicine and biologyauthors
Field HJ,Mickleburgh Idoi
10.1007/978-1-4614-5037-5_7subject
Has Abstractpub_date
2013-01-01 00:00:00pages
145-59eissn
0065-2598issn
2214-8019journal_volume
767pub_type
杂志文章,评审abstract：:The function and characteristics of mouse folylpolyglutamate synthetase have been examined. Folate polyglutamates were poor substrates for the efflux mechanism for monoglutamates in L1210 mouse leukemia cells, with negligible loss of preformed folate polyglutamates to the medium over four hours. Disruption of folate m...
journal_title：Advances in experimental medicine and biology
pub_type： 杂志文章
doi：10.1007/978-1-4757-5241-0_24
更新日期：1983-01-01 00:00:00
abstract：:We have shown that the PC12 cell line is an excellent model system for investigations of the molecular and cellular processes involved in O2-chemosensitivity. We have identified an O2-sensitive K channel in this cell line that mediates membrane depolarization, an increase in intracellular free Ca2+, and dopamine relea...
journal_title：Advances in experimental medicine and biology
pub_type： 杂志文章,评审
doi：10.1007/978-1-4615-5891-0_20
更新日期：1996-01-01 00:00:00
abstract：:Terminal Transferase (TdT), Adenosine Deaminase (ADA), immunological membrane markers, cytochemical reactivity and cytogenetics were analyzed in 226 patients with ALL, AUL and AML, in 70 patients with CML and in 3 cases of Ph' positive acute leukemia presenting as ALL. TdT was tested in peripheral blood and bone marro...
journal_title：Advances in experimental medicine and biology
pub_type： 杂志文章
doi：10.1007/978-1-4684-8929-3_24
更新日期：1982-01-01 00:00:00
abstract：:Hypertension is common yet difficult to manage in the hemodialysis patients population. This chapter discusses various aspects of this problem including its prevalence, distinctive pathophysiology, methods of diagnosis and pharmacological and non pharmacological treatment approaches. The topic is relevant to any healt...
journal_title：Advances in experimental medicine and biology
pub_type： 杂志文章,评审
doi：10.1007/5584_2016_88
更新日期：2017-01-01 00:00:00
abstract：:Induced pluripotent stem cells (iPSCs) offer great promise in the areas of disease modeling, basic research, drug development, and regenerative medicine. Much of their value comes from the fact that they can be used to create otherwise inaccessible cell types, such as cardiomyocytes, which are genetically matched to a...
journal_title：Advances in experimental medicine and biology
pub_type： 杂志文章,评审
doi：10.1007/5584_2019_350
更新日期：2020-01-01 00:00:00
abstract：:Lead (Pb2+) is a developmental neurotoxicant that causes lifelong cognitive dysfunctions. In particular, Pb2+-induced frontoexecutive dysfunctions emerge later in life when the cortex is fully myelinated, thereby permitting the ability to assess the extent to which Pb2+ has developmentally impacted higher order cognit...
journal_title：Advances in experimental medicine and biology
pub_type： 杂志文章
doi：10.1007/978-981-13-8023-5_70
更新日期：2019-01-01 00:00:00
abstract：:RNA granules are microscopically visible cellular structures that aggregate by protein-protein and protein-RNA interactions. Using stress granules as an example, we discuss the principles of RNA granule formation, which rely on the multivalency of RNA and multi-domain proteins as well as low-affinity interactions betw...
journal_title：Advances in experimental medicine and biology
pub_type： 杂志文章
doi：10.1007/978-3-319-29073-7_11
更新日期：2016-01-01 00:00:00
abstract：:Studies have shown that the renal tubular epithelium adapts to alterations in the sulfur amino acid composition of the diet. The renal adaptive response has been described in man, mouse, rat, dog, and pig. The observed phenomenon involves increased or decreased initial rate activity of the NaCl-dependent taurine trans...
journal_title：Advances in experimental medicine and biology
pub_type： 杂志文章
doi：10.1007/978-1-4899-0117-0_33
更新日期：1998-01-01 00:00:00
abstract：:We have shown that bovine HMW kininogen remarkably accelerates the activation of Factor XII and prekallikrein in the presence of kaolin, adsorbing on kaolin through the fragment 1.2 region and forming a complex with prekallikrein through the light chain region (Sugo et al., 1980; Ikari et al., 1981). The present study...
journal_title：Advances in experimental medicine and biology
pub_type： 杂志文章
doi：
更新日期：1983-01-01 00:00:00
abstract：:The first systematic multi-center study of the clinical use of EPR oximetry has begun, with funding as a PPG from the NCI. Using particulate oxygen sensitive EPR, materials in three complementary forms (India Ink, "OxyChips", and implantable resonators) the clinical value of the technique will be evaluated. The aims i...
journal_title：Advances in experimental medicine and biology
pub_type： 杂志文章,多中心研究
doi：10.1007/978-3-319-38810-6_13
更新日期：2016-01-01 00:00:00
abstract：:The effects of audiovisual stimulation on the temporal patterns of V(T), T(I), T(E) were studied in 11 healthy subjects. 75 datasets of steady-state breathing each of eight minutes in duration were obtained during low wakefulness (lying still, eyes closed), low wakefulness with calibrated thermal pain stimulation and ...
journal_title：Advances in experimental medicine and biology
pub_type： 杂志文章
doi：10.1007/978-0-387-73693-8_83
更新日期：2008-01-01 00:00:00
abstract：:STAT (signal transducers and activators of transcription) are latent cytoplasmic transcription factors that function as downstream effectors of cytokine and growth factor receptor signaling. The canonical JAK/STAT signaling pathway involves the activation of Janus kinases (JAK) or growth factors receptor kinases, phos...
journal_title：Advances in experimental medicine and biology
pub_type： 杂志文章,评审
doi：10.1007/978-94-007-4719-7_10
更新日期：2013-01-01 00:00:00
abstract：:Despite diverse and changing extracellular environments, fungi maintain a relatively constant cytosolic pH and numerous organelles of distinct lumenal pH. Key players in fungal pH control are V-ATPases and the P-type proton pump Pma1. These two proton pumps act in concert with a large array of other transporters and a...
journal_title：Advances in experimental medicine and biology
pub_type： 杂志文章,评审
doi：10.1007/978-3-319-25304-6_3
更新日期：2016-01-01 00:00:00
abstract：:Feedback from muscle afferents is essential for locomotion to be functional under changing external conditions. In this article, we review the role of afferent feedback in adapting locomotor activity to transient and more sustained changes in sensory input in reduced and walking cat preparations. Much of the work on m...
journal_title：Advances in experimental medicine and biology
pub_type： 杂志文章,评审
doi：10.1007/978-1-4615-0713-0_40
更新日期：2002-01-01 00:00:00
abstract：:The tumor microenvironment (TME) represents a milieu that enables tumor cells to acquire the hallmarks of cancer. The TME is heterogeneous in composition and consists of cellular components, growth factors, proteases, and extracellular matrix. Concerted interactions between genetically altered tumor cells and genetica...
journal_title：Advances in experimental medicine and biology
pub_type： 杂志文章,评审
doi：10.1007/978-3-319-24932-2_5
更新日期：2016-01-01 00:00:00
abstract：:To develop an osteochondral tissue regeneration strategy it is extremely important to take into account the multiscale organization of the natural extracellular matrix. The structure and gradients of organic and inorganic components present in the cartilage and bone tissues must be considered together. Another critica...
journal_title：Advances in experimental medicine and biology
pub_type： 杂志文章,评审
doi：10.1007/978-3-319-76711-6_6
更新日期：2018-01-01 00:00:00
abstract：:The analysis of circulating free carnitine and acyl-carnitines provides a powerful selective screening tool for genetic defects in mitochondrial fatty acid oxidation and defects in the catabolism of branched chain amino acids. Using electrospray tandem mass spectrometry (ESI/MS/MS) we developed a sensitive quantitativ...
journal_title：Advances in experimental medicine and biology
pub_type： 杂志文章
doi：10.1007/0-306-46818-2_38
更新日期：1999-01-01 00:00:00
abstract：:Acute disseminated encephalomyelitis (ADEM) is a disorder of the central nervous system (CNS) characterized by an acute event, typically with encephalopathy, in which diffuse CNS involvement occurs. It may follow an infectious event and occurs more commonly in young children. Pulse steroid treatment is frequently used...
journal_title：Advances in experimental medicine and biology
pub_type： 杂志文章,评审
doi：10.1007/978-1-4614-0653-2_1
更新日期：2012-01-01 00:00:00
abstract：:In order to clarify the significance of the renal kallikrein(KAL)-kinin(KIN) system and prostaglandins (PG) in exaggerated natriuresis in essential hypertensives, the effect of acute sodium load on urinary KAL, KIN, PG, and renal water and sodium handling were investigated in normotensives (NT) and patients with essen...
journal_title：Advances in experimental medicine and biology
pub_type： 杂志文章
doi：10.1007/978-1-4757-0154-8_42
更新日期：1986-01-01 00:00:00
abstract：:One of the most prevalent of cancers, breast cancer, is characterized by hormonal control of its growth. Expression of the estrogen receptor (ER) in MCF-7 breast cancer cells appears to be a complex process involving multiple steps subject to hormonal regulation by estrogen. Treatment of MCF-7 cells with estradiol res...
journal_title：Advances in experimental medicine and biology
pub_type： 杂志文章
doi：10.1007/978-1-4615-2926-2_11
更新日期：1993-01-01 00:00:00
abstract：:Drosophila melanogaster is since decades the most important invertebrate model. With the publishing of the genome sequence, Drosophila also became a pioneer in (neuro)peptide research. Neuropeptides represent a major group of signaling molecules that outnumber all other types of neurotransmitters/modulators and hormon...
journal_title：Advances in experimental medicine and biology
pub_type： 杂志文章,评审
doi：10.1007/978-1-4419-6902-6_10
更新日期：2010-01-01 00:00:00
abstract：:Endometrial cancer is a frequently occurring gynecological disorder. Estrogen-dependent endometrioid carcinoma is the most common type of gynecological cancer. One of the major pathologic phenomena of endometrial cancer is the loss of estrogen (E2) and progesterone (P4) control over uterine epithelial cell proliferati...
journal_title：Advances in experimental medicine and biology
pub_type： 杂志文章
doi：10.1007/978-3-319-43139-0_8
更新日期：2017-01-01 00:00:00
abstract：:Some species avoid low-frequency masking by shifting their calls to higher frequencies. We addressed the hypothesis that Pagophilus groenlandicus (harp seals) will make more high-frequency underwater calls to avoid low-frequency conspecific masking as calling rates increase. The spectral shapes at high and low calling...
journal_title：Advances in experimental medicine and biology
pub_type： 杂志文章
doi：10.1007/978-1-4939-2981-8_143
更新日期：2016-01-01 00:00:00
abstract：:The diffusion coefficients of cell membranes of pneumocytes plus endothelial cells, cytosol plus blood plasma, erythrocyte membranes, and hemoglobin solution in erythrocytes were estimated from the fluorometrically measured membrane viscosity. The time course of oxygen partial pressure distribution was numerically cal...
journal_title：Advances in experimental medicine and biology
pub_type： 杂志文章
doi：10.1007/978-1-4615-9510-6_7
更新日期：1988-01-01 00:00:00
abstract：:We have found that apparent Ki values of some, but not all, carboxyalkyl-dipeptide inhibitors of angiotensin converting enzyme decrease as a function of incubation time. The most potent of the ACE inhibitors tested so far is RAC-X-65 (N-[1(S)-carboxy-3-carboxanilidiopropyl]-L-Ala-L-Pro). When RAC-X-65 is not preincuba...
journal_title：Advances in experimental medicine and biology
pub_type： 杂志文章
doi：10.1007/978-1-4684-5143-6_57
更新日期：1986-01-01 00:00:00
abstract：:The CRISPR/Cas9 system has emerged as a powerful tool to edit the genome. Among many applications, the system generates the exciting possibility of engineering small and large portions of chromosomes to induce a variety of structural alterations such as deletions, inversions, insertions and inter-chromosomal transloca...
journal_title：Advances in experimental medicine and biology
pub_type： 杂志文章
doi：10.1007/978-981-13-0593-1_4
更新日期：2018-01-01 00:00:00
abstract：:WEHI-231, a murine B-cell lymphoma, readily undergoes programmed cell death following surface immunoglobulin (Ig) cross-linking [1]. Ceramide has been shown to induce apoptosis in WEHI-231 following its exposure to anti-lg antibodies, dexamethasone, and irradiation [2]. Recently, Haimovitz-Friedman et al. have demonst...
journal_title：Advances in experimental medicine and biology
pub_type： 杂志文章
doi：10.1007/978-1-4899-0274-0_5
更新日期：1996-01-01 00:00:00
abstract：:We focus on dynamical descriptions of short-term synaptic plasticity. Instead of focusing on the molecular machinery that has been reviewed recently by several authors, we concentrate on the dynamics and functional significance of synaptic plasticity, and review some mathematical models that reproduce different proper...
journal_title：Advances in experimental medicine and biology
pub_type： 杂志文章,评审
doi：10.1007/978-3-319-62817-2_3
更新日期：2017-01-01 00:00:00
abstract：:Our new method is comparable to the standard, "open-end" tonometer system and incorporates all its abilities to monitor oxygen tension and perfusion. The new device has the advantage of being completely sealed, providing a true, continuous direct measurement over several days, with freedom of movement for the patient ...
journal_title：Advances in experimental medicine and biology
pub_type： 杂志文章
doi：10.1007/978-1-4615-9510-6_31
更新日期：1988-01-01 00:00:00
abstract：:Opioid analgesics remain the most effective and widely used analgesics for the management of moderate to severe pain, including cancer pain and chronic non-cancer pain. However, the efficacy of long-term opioid analgesics is attenuated by tolerance and/or hyperalgesia after long-term use, preventing adequate pain reli...
journal_title：Advances in experimental medicine and biology
pub_type： 杂志文章
doi：10.1007/978-981-13-1756-9_11
更新日期：2018-01-01 00:00:00
